Intestinal lymphangiectasia in children: A favorable response to dietary modifications

Intestinal lymphangiectasia (IL) is a rare disease characterized by dilatation of intestinal lymphatics. It can be classified as primary or secondary according to the underlying etiology. The clinical presentations of IL are pitting edema, chylous ascites, pleural effusion, acute appendicitis, diarrhea, lymphocytopenia, malabsorption, and intestinal obstruction. The diagnosis is made by intestinal endoscopy and biopsies. Dietary modification is the mainstay in the management of IL with a variable response. Here we report 2 patients with IL in Bahrain who showed positive response to dietary modification.Intestinal lymphangiectasia (IL) is a rare1-4 benign disease characterized by focal or diffuse dilation of the mucosal, submucosal, and subserosal lymphatics.2,5 In addition to being an important cause of protein losing enteropathy (PLE),6 IL is frequently associated with extraintestinal lymphatic abnormalities.5 Depending on the underlying pathology IL can be classified as primary or secondary disease.1,2,4,5 Primary IL (PIL) probably represents a congenital disorder of mesenteric lymphatics.1,3 The IL can be secondary to diseases like constrictive pericarditis, lymphoma, sarcoidosis, and scleroderma.1 A secondary disorder should always be ruled out before labeling IL as primary, this is by testing for proteinuria, rheumatic, neoplastic, and parasitic infection.1,3 Recently, a functional form of PIL with typical endoscopic and pathological findings but without clinical symptoms has been reported.3 The clinical presentations of IL are pitting edema, chylous ascites, pleural effusion, acute appendicitis, diarrhea, lymphocytopenia, malabsorption, and intestinal obstruction.1,2,4 Palliative treatment with lifelong dietary modification is the most effective and widely prescribed therapy.6 Limiting the dietary fat intake reduces chyle flow and therefore, protein loss.1 Once protein level is within the normal range, recurrence of enteric protein loss can be prevented by total parenteral nutrition (TPN) and medium chain triglycerides (MCT).1 In cases of secondary IL, treating the underlying primary disorder may be curative.2 Although the therapeutic approach for this disorder have gained a lot of attention lately, few studies have considered the therapeutic effects, nutritional condition, and long-term results in PIL patients.4 Here, we report 2 patients with PIL who were diagnosed by endoscopy and biopsy, and showed positive response to dietary modifications. We present these particular cases to highlight the effect of dietary modifications on the clinical status of patients with IL.     

Long term prognosis of women with gestational diabetes in a multiethnic population

Aim

To assess the glucose tolerance of South Asian and Caucasian women with previous gestational diabetes mellitus (GDM).

Method

A retrospective follow‐up study of 189 women diagnosed with GDM between 1995 and 2001. Glucose tolerance was reassessed by oral glucose tolerance test at a mean duration since pregnancy of 4.38 years.

Results

South Asian women comprised 65% of the GDM population. Diabetes developed in 36.9% of the population, affecting more South Asian (48.6%) than Caucasian women (25.0%). Women developing diabetes were older at follow‐up (mean (SD) 38.8 (5.7) vs 35.9 (5.6) years; p<0.05) and had been heavier (body mass index 31.4 (6.3) vs 27.7 (6.7) kg/m²; p<0.05), more hyperglycaemic (Gl₀ 6.5 (1.7) vs 5.2 (1.1) mmol/l; p<0.01: G₁₂₀ 11.4 (3.3) vs 9.6 (1.8) mmol/l; p<0.01: HbA1c 6.4 (1.0) vs 5.6 (0.7); p<0.01) and more likely to require insulin during pregnancy (88.1% vs 34.0%; p<0.01). Future diabetes was associated with and predicted by HbA1c taken at GDM diagnosis in both South Asian (odds ratio 4.09, 95% confidence interval 1.35 to 12.40; p<0.05) and Caucasian women (OR 9.15, 95% CI 1.91 to 43.87; p<0.01) as well as by previously reported risk factors of increasing age at follow‐up, pregnancy weight, increasing hyperglycaemia and insulin requirement during pregnancy.

Conclusion

GDM represents a significant risk factor for future DM development regardless of ethnicity. Glycated haemoglobin values at GDM diagnosis have value in predicting future diabetes mellitus.Gestational diabetes mellitus (GDM) is defined as abnormal carbohydrate tolerance that is diagnosed or first recognised in pregnancy¹ and affects approximately 5% of pregnancies.² However, the prevalence depends on the population studied and the diagnostic criteria used³ with an increased frequency of GDM when less stringent diagnostic criteria are used and in ethnic groups who traditionally have a higher rate of type 2 diabetes.^4,5,6 Differences in the prevalence of GDM reflect the background susceptibility of individual ethnic groups^2,7 and possibly a different stage within the natural history of diabetes at the time of pregnancy.⁸Previous GDM confers an increased risk of subsequent diabetes mellitus such that 50% of women will have diabetes mellitus after 10 years.^9,10 Several antenatal and maternal factors have been shown to predict this^11,12,13 and identification of these during the screening of women with GDM may lead to more effective targeting of strategies for primary prevention of diabetes in local populations.^3,14 Glycated haemoglobin (HbA1c), while convenient to measure, has little sensitivity in making the diagnosis of GDM¹⁵ and has been little studied as a risk marker for predicting future diabetes.A number of studies have suggested that diabetes following GDM develops more rapidly in non‐Caucasian groups.^5,16,17 A recent meta‐analysis, however, suggested that differences between the ethnic groups studied could largely be explained by standardising diagnostic criteria, duration of follow‐up and patient retention.¹⁸ The Leicestershire population consists of a significant minority of women from the Indian subcontinent who have higher rates of glucose intolerance both in and out of pregnancy.¹⁹ This study examined the development of glucose intolerance and its pregnancy associations in this ethnically mixed population.     

Kimura disease: No age or ethnicity limit

Kimura disease is a chronic inflammatory disease that mainly manifests as a lump in the cervical region. Although the underlying pathophysiology is not clear yet, the diagnosis can be established based on specific histopathological characteristics. The first case of this disease was described in China, as well as the majority of subsequent cases that were also described in the Far East countries made Kimura disease traditionally a disease of adult patients of Asian descent. This report describes the occurrence of Kimura disease in pediatric non-Asian patient with a similar clinicopathologic presentation.Although Kimura disease can be grouped under inflammatory disease of chronic nature, the underlying cause is still to be investigated. The disease usually present with enlarged, but painless cervical lymph node or subcutaneous masses in the cervical region.1,2 Clinical and histological characteristics of Kimura disease (primary allergic reaction or an alteration of immune regulation) help to differentiate it from angiolymphoid hyperplasia with eosinophilia (an arteriovenous malformation with secondary inflammation mostly involving dermal or subcutaneousparts), which were previously thought to be the same disease.1,2 Most cases have been reported in adult patients from the Far East of Asia.1,2 Elevation of inflammatory mediators that are usually elevated in autoimmune disorders made hypersensitivity a possible underlying pathophysiological mechanism of this disease.1,2 Patients usually present with non-tender mass in the cervical region with elevated eosinophils count and high levels of serum immunoglobulin type E (IgE).2 Unfortunately, there are no specific radiological characteristics of that disease.2 The only way to diagnose Kimura disease is through its histopathologic features, which necessitate a surgical biopsy.1,2 Treatment usually start with medical therapy and if that fail or show no spontaneous resolution then surgical excision would be the choice at that point with radiotherapy reserved for selected cases.1,2 The main objective of presenting this case report is to emphasize that Kimura disease can involve pediatric Saudi patients in contrast to what was historically described as a disease of adult Asian only. Secondary, it is to support what had been reported of occurrence of the disease in non-Asian patient with a similar clinicopathologic presentation of the Asian patients.2,3     

Management of rhino-orbital mucormycosis

Mucormycosis is an uncommon acute invasive fungal infection that affects immunocompromised patients. It progresses rapidly and has poor prognosis if diagnosed late. Early detection, control of the underlying condition with aggressive surgical debridement, administration of systemic and local antifungal therapies, hyperbaric oxygen as adjunctive treatment improves prognosis and survivability.Mucormycosis also known as zygomycosis and phycomycosis is an uncommon, opportunistic, aggressive fatal fungal infection caused by fungi of the order Mucorales, frequently among immunocompromised patients. This fungal infection begins from the sinonasal mucosa after inhalation of fungal spores; the aggressive and rapid progression of the disease may lead to orbital and brain involvement.1-4 In the past, the mortality rate of the rhino-cerebral type was 88%, but recently the survival rate of rhino-cerebral mucormycosis averages 21-73% depending on the circumstances.1 Mucormycosis is classified according to anatomical site into rhino-cerebral, which is the most common, central nervous system, pulmonary, cutaneous, disseminated, and miscellaneous.1,2,4-6 The rhino-orbito-cerebral is the most common form of mucormycosis.3 The most common predisposing factor is uncontrolled diabetes mellitus (DM), especially when the patient has a history of ketoacidosis, these species thrive best in a glucose rich and acidic environment.3,4,6,7 Immunosuppressive drugs such as steroids, neutropenia, acquired immune deficiency syndrome, dialysis patients on deferoxamine, malnutrition, hematologic malignancy, and organ transplant patients are also at risk of affection by the fungi.1,4-7 This case report describes a case of rhino-orbital mucormycosis affecting a diabetic female with good prognosis and satisfactory healing. Our objective in presenting this particular case is to emphasize that early diagnosis and proper management leads to good prognosis and high survivability.     

X-ray repair cross-complementing protein 1 and 3 polymorphisms and susceptibility of breast cancer in a Jordanian population

Objectives:

To elucidate the contribution of x-ray repair cross-complementing (XRCC) protein 1 399Gln, XRCC3 241M, and XRCC3-5’-UTR polymorphisms to the susceptibility of breast cancer (BC) in a Jordanian population.

Methods:

Forty-six formalin fixed paraffin embedded tissue samples from BC diagnosed female patients, and 31 samples from the control group were subjected to DNA sequencing. Samples were collected between September 2013 and December 2014.

Results:

The XRCC1 Arg399Gln genotype did not exhibit any significant correlation with the susceptibility of BC (odds ratio [OR]=1.45, 95% confidence interval [CI]: 0.60-3.51) (p=0.47). Likewise, XRCC3 M241T genotype did not show significant correlation with BC (OR=2.02, 95% CI: 0.50-8.21) (p=0.40). However, distribution of XRCC3-5’UTR (rs1799794 A/G) genotype showed a significant difference between the patient and control group (OR=0.73, 95% CI: 0.06-8.46) (p=0.02).

Conclusion:

The XRCC3-5’UTR (rs1799794) G allele frequency was higher in cancer patients while XRCC1 (rs25487) and XRCC3 (rs861539) did not show any significant correlation with susceptibility of BC in the selected Jordanian population. Contribution of other environmental factors should be studied in future works, as well as the response of cancer therapy.Breast cancer (BC) incidence in Jordan has been estimated at 1,237 cases in 2012, with a prevalence of 4,260 cases over 5 years, and mortality rate up to 426 cases.1 Genetic predisposition contributes to less than 10% of BC cases, which raises a demand for further research into new genetic markers of BC risks.2 Fewer than 5% of BC cases have been found to be mutated at breast cancer 1 (BRCA1) early onset and BRCA2 genes, and approximately 40% of familial BC families have been identified for genetic predisposition.3 Unfortunately, mammalian cells are habitually exposed to genotoxic agents, such as ionizing radiation that can lead to DNA damage. Many double strand break,4 and single strand break (SSB) repairing proteins have been identified including DNA repair protein homolog, or RAD tecombinase, or x-ray repair cross-complementing (XRCC)s family proteins.5 Deficiency in repairing system might contribute to cancer development due to the loss of genetic integrity and genome instability.6 Mutation in DNA repair proteins is very rare.7 Therefore, many studies have been conducted to evaluate the role of allelic polymorphisms in DNA repair genes involved in cancers development.8,9 Genetic polymorphisms in DNA repair genes XRCC1, and XRCC3 have been screened to find an association with the risk of BC.10-12 Studies have demonstrated an association between XRCC1 and XRCC3 polymorphisms, and certain cancers subsuming colorectal cancer,13 lung cancer,14 pancreatic cancer,15 head and neck cancer,16 gastric cancer,17 esophageal cancer,18 melanoma skin cancer,19 oral squamous cell carcinomas,20 lung cancer risk,21 bladder cancer,22 and BC.23 Furthermore, a meta-analysis study supported the contribution of XRCC1 Arg399Gln polymorphism in susceptibility of BC in the American population.24 On the other hand, no relationship has been found between XRCC1 and XRCC3 polymorphisms and the risk of BC,25 lung cancer,26 bladder cancer,27 prostate cancer,28 lung cancer risk,29 cutaneous malignant melanoma,30 furthermore, it may decrease the risk for myeloblastic leukemia31 and non-melanoma skin cancer.32 Alcoholism, abortion, and non-breast feeding have been associated with increased risk of BC with contribution of XRCC1 399Gln and XRCC3 T241M polymorphisms.11 Moreover, family history,12 age group,33 polycyclic aromatic hydrocarbon-DNA adducts, fruit and vegetable and antioxidant intake, and non-smokers have been suggested to be associated with the risk of BC in interaction with XRCC1 or XRCC3 polymorphisms.34 The aim of the current study was to elucidate the contribution of XRCC1 399Gln, XRCC3 241M and XRCC3-5’-UTR polymorphisms in the susceptibility of BC in the Jordanian population. This study is intended to establish a reference point for future single nucleotide polymorphism (SNP) studies in the Jordanian population, which may contribute to the development of a national cancer database.     

A cross-sectional study of anxiety and marital quality among women with breast cancer at a university clinic in western Saudi Arabia

Objectives:

To examine relationship between the quality of marital relationship and anxiety among women with breast cancer (BC) in the Kingdom of Saudi Arabia (KSA).

Methods:

This cross-sectional study recruited a consecutive series of 49 married women with BC seen in the Al-Amoudi Breast Cancer Center of Excellence at King Abdulaziz University, Jeddah, KSA in early 2013. Participants completed the Hospital Anxiety and Depression Scale, Spouse Perception Scale, and Quality of Marriage Index forms, and answered questions on demographic and cancer characteristics.

Results:

Anxiety symptoms indicating “possible” anxiety disorder were present in 10.4% and “probable” anxiety disorder in 14.6% (25% total). No significant relationship was found between the quality of marital relationship and anxiety symptoms (B=-0.04, standard error=0.05, t=-0.81, p=0.42). Anxiety was primarily driven by low education, poor socioeconomic status, and young age.

Conclusion:

Anxiety symptoms are prevalent among married women with BC seen in a university-based clinic in the KSA. Further research is needed to determine whether a diagnosis of BC adversely affects marital relationship, and whether this is the cause for anxiety in these women.Breast cancer (BC) is the most common cause of cancer death in women worldwide,1 and the Kingdom of Saudi Arabia (KSA) is no exception.2 Breast cancer has become a particular problem in Arab countries due to its late stage at presentation and its increased occurrence among young women.3 Both during and after treatment, even if the cancer goes into remission, concerns regarding recurrence, effect on the marital relationship, and frequent medical visits for monitoring, often result in high levels of anxiety (including post-traumatic stress-like symptoms).4-8 Anxiety and other mood symptoms are not benign in women with BC, as they are associated with increased mortality and cancer recurrence.9,10Studies in Western countries (United States, Canada, England, Australia, and Germany) indicate a prevalence of significant anxiety ranging from 4-45% in BC patients, depending on anxiety measure, cutoff score, geographical region, and time since diagnosis11-14 (compared with 15-37% of cancer patients in general with anxiety during the first year after diagnosis).15 The most commonly used measure of anxiety symptoms in BC patients is the Hospital Anxiety and Depression Scale (HADS), which assesses for “possible” and “probable” anxiety disorder (with a sensitivity and specificity of approximately 80%).12,16,17 Using this measure, the prevalence of “probable” anxiety disorder in BC patients ranges from 2-23% and “possible” anxiety disorder is present in an additional 19-22% (21-45% combined).11,13,18 Although factors that increase risk of anxiety in women with BC are poorly understood, a few studies largely from Western countries report more symptoms in younger persons and Caucasians, immigrants, those with lower education, later disease stage, and lower social support.8,11,13,19 In one of the few studies from an Eastern country,20 anxiety levels among BC patients from Bangkok, Thailand, were significantly higher among those with poor problem solving skills, more pain and fatigue, and poorer family functioning. Although research is limited almost entirely to the US and other Western countries, studies indicate that support from a spouse (especially emotional support) improves the adjustment of women to BC,21-25 and may even impact survival.26 Not all studies, however, report that having a marital partner buffers against the stress of BC.27,28 The demands of caregiving, the effects of BC and its treatments on sexual relationship, and coping with psychological changes in a BC patient can all lead to lower well-being in a spouse, and decrease his ability to provide support.24 Our exhaustive review of the literature uncovered several studies that have examined the prevalence of emotional reactions to BC in the Middle East, finding that 19-73% of women had significant anxiety symptoms.22,29-34 In those studies, anxiety was associated with poorer physical functioning, the presence of metastatic disease, higher education, lower social support, duration of marriage, and spouse’s level of anxiety. With regard to KSA, there has been a significant increase in the incidence of BC, which occurs at a younger age than in Western countries.35 A recent review of research on coping with BC, however, revealed not a single study from KSA.36 Our review identified only 2 studies37,38 that examined the prevalence or correlates of anxiety in Saudi cancer patients (none specifically in BC), and only one study39 that examined attitudes of Saudi males toward BC. The first study examined anxiety in 30 hospitalized patients with cancer (9 with BC) at the King Khalid National Guard Hospital in Jeddah, KSA.37 Researchers found that anxiety symptoms assessed by the Hamilton Anxiety Scale were significantly higher in cancer patients compared with 39 patients with a range of chronic illnesses; 3 patients with cancer (10%) had a clinical diagnosis of generalized anxiety disorder based on Diagnostic and Statistical Manual of Mental Disorders, 4th edition (DSM-IV) criteria. The second study examined non-pain symptoms in 124 cancer patients (27% with BC) at King Faisal Specialist Hospital in Riyadh, KSA.38 The most frequently reported non-pain symptoms were fatigue (80%), loss of appetite (72%), dry mouth (69%), and anxiety (61%). Finally, researchers examined attitudes toward BC among males accompanying female patients to outpatient clinics at King Abdulaziz Hospital in Jeddah, KSA. When men were asked what they would do if their wives were diagnosed with BC, 9.4% said they would leave their wives.39Given the current knowledge gap on this subject in KSA, we decided to: 1) determine the prevalence of anxiety symptoms in married women seen in an urban-based university outpatient clinic in Jeddah; 2) identify the correlates of anxiety symptoms (especially marital quality [MQ]); and 3) determine whether the relationship between MQ and anxiety differed between Saudi nationals and immigrants. We hypothesized that anxiety symptoms would be prevalent, that higher MQ would be strongly and inversely related to anxiety symptoms, and that this relationship would be particularly strong in women who were Saudi nationals (where cultural factors might have the most influence).     

Screening for Addison's disease in patients with type 1 diabetes mellitus and recurrent hypoglycaemia

Background

Addison''s disease may present with recurrent hypoglycaemia in subjects with type 1 diabetes mellitus. There are no data, however, on the prevalence of Addison''s disease presenting with recurrent hypoglycaemia in patients with diabetes mellitus.

Methods

Three year retrospective study of diabetic patients with “unexplained” recurrent hypoglycaemia investigated with a short Synacthen test to exclude adrenocortical insufficiency.

Results

95 patients with type 1 diabetes mellitus were studied. Addison''s disease was identified as the cause of recurrent hypoglycaemia in one patient with type 1 diabetes mellitus.

Conclusion

Addison''s disease is a relatively rare but remedial cause of recurrent hypoglycaemia in patients with type 1 diabetes mellitus. A low threshold for investigating patients with type 1 diabetes mellitus and recurrent hypoglycaemia to detect Addison''s disease is therefore suggested.Addison''s disease may present as recurrent hypoglycaemia in patients with type 1 diabetes mellitus^{1,2,3,4,5,6,7} and it is recommended that diabetic patients with unexplained recurrent hypoglycaemia be screened for Addison''s disease.⁸ There are, however, no data on the prevalence of Addison''s disease presenting with recurrent hypoglycaemia in patients with diabetes. We report on the prevalence of Addison''s disease presenting with recurrent hypoglycaemia in patients with type 1 diabetes mellitus.     

Pemphigus and pregnancy: Analysis and summary of case reports over 49 years

Pemphigus is a group of immune-mediated bullous disorders, which often cause fragile blisters and extensive lesions of the skin or mucous membranes, such as in the mouth. This disease could be life-threatening in some cases. During pregnancy, its condition will become more complicated due to the change in the mother’s hormone level and the effect of drug therapy on both the mother and her fetus. Thus, it will be more difficult to identify the clinical manifestations and to establish the treatment plan. In this article, we present a comprehensive review of pemphigus and pregnancy by analyzing 47 cases of pemphigus reported between 1966 and 2014, with diagnosis before or during pregnancy. The aim of this study is to make a comprehensive review of pemphigus and pregnancy, provide organized and reliable information for obstetricians, dermatologists, physicians, and oral medicine specialists.Pemphigus is characterized by widely distributed bullae and erosions on the skin and mucosa membranes. There are mainly 3 types of pemphigus: Pemphigus vulgaris (PV), Pemphigus foliaceus (PF), and other variants of pemphigus.1,2 The pathogenesis of pemphigus is associated with autoantibodies directed against transmembrane glycoproteins of desmosomes, which causes steric hindrance to homophilic adhesion of desmogleins, and results in the formation of Dsg1-depleted desmosomes in PF and Dsg3-depleted desmosomes in PV.3,4 Pemphigus usually affects the elderly, and genetics play an important role in predisposition.5,6 Pemphigus could involve one or more mucosae, while PV often shows extensive lesions of the oral mucosa.7,8 When it occurs in pregnancy, the condition becomes more complex.9 Early diagnosis and individually adjusted therapy are needed to avoid any risk for mother or child.10 The purpose of this article is to make a comprehensive review of the pemphigus and pregnancy, and provide organized and reliable information for clinicians.

Basic demographics

The existing reseasrch is mainly focused on case reports and retrospective studies. References were retrieved by an electronic search strategy “(pemphigus [MeSH Terms]) AND pregnancy [MeSH Terms] Filters: Case Reports” on PubMed, and a total of 62 cases were reviewed. Of the 62 cases, 14 were excluded based on abstract, which indicated discussion about gestational pemphigoid, and 7 were excluded because they were non-English. Finally, we included 41 relevant case reports according to their titles and abstracts. These 41 case reports between 1966 and 2014 involved 47 women identified with pemphigus before (n=21 cases) or during pregnancy (n=26 cases). These cases of pemphigus and pregnancy have been reported in different populations, Asia, Europe, and North America, with more than in Africa, South America, and Oceania (Figure 1). A recent study from the United Kingdom has suggested an incidence of PV of 0.68 cases per 100,000 persons per year. The incidence varies in different areas, being more common in the Near and Middle East than in Western Europe and North America.11-14Open in a separate windowFigure 1Regional distribution of 47 cases of pemphigus and pregnancy between 1966 and 2014.We analyzed the characteristics of 21 patients with pemphigus diagnosed before pregnancy. Among them, 71.4% were diagnosed as PV, 19% as PF, 4.8% as Pemphigus vegetans, while the remaining was indefinite. The age of onset of pemphigus was generally 20-42 years old (mean age 27.35±5.73), with a mean interval of 3.16±2.11 years between disease onset and pregnancy. The pemphigus course was characterized by exacerbation (61.9%), improvement (9.5%), and remaining stable (28.6%) during the pregnancy. The newborn status is meaningful for our conclusion. The incidence of neonatal pemphigus was as high as 57.1% (including 38.1% of PV and 19% of PF). In contrast, the percentage of healthy neonates was only 33.3%, which may be considered to be publication bias (15-31

Table 1

Characteristics of 21 patients with pemphigus diagnosed between 1966 and 2013.Open in a separate windowIt seems to be quite a rare phenomenon that pregnancy as a triggering factor of PV seems to be quite a rare phenomenon.13 4,14,19,32-52

Table 2

Characteristics of 26 patients with pemphigus diagnosed during pregnancy between 1966 and 2013.Open in a separate window

Effects on the mother

If a pregnant woman becomes sick (such as pemphigus), she is more likely to suffer from disorders of the neuroendocrine system and immune system due to the state of high pressure.53 According to the current study, the mother’s condition may exacerbate, enter into remission, or remain stable during the pregnancy.54 The disease is aggravated most likely during the first, second trimester, and postpartum, then is relived during the third trimester.15 This may be due to the increased level of endogenous corticosteroid hormone chorion and subsequent immunosuppression.40,55 Although some literature reports the postpartum flare of pemphigus due to the rapid drop of corticosteroid hormones levels, the postpartum status in our study was optimistic, only 2 cases (9.5%) of pemphigus diagnosed before pregnancy and 8 cases (30.8%) of pemphigus diagnosed during pregnancy exacerbated after delivery.19,56 However, some patients with pemphigus during pregnancy may not show any obvious changes, especially those patients in remission.9,15

Effects on the mode of delivery

Goldberg et al32 and Fainaru et al14 indicated that the trauma of vaginal delivery can result in extension and deterioration of the wound. In a cesarean section, patients who receive long-term steroid therapy will increase the risk, and the disease itself, and corticosteroid therapy may complicate wound healing. Therefore, delivery by cesarean section is the absence of additional benefits. Except for obstetric contraindications, vaginal delivery is recommended. Although it is a potential risk that local blisters may result in passive transfer of antibodies to the fetus through the breast milk, breastfeeding is not contraindicated.

Effects on the pregnancy outcome

Pregnancy outcome includes live birth, stillbirth, spontaneous abortion, and induced abortion.57 Pemphigus vulgaris in pregnancy may result in abortion, fetal growth retardation, intrauterine death, premature delivery, and in approximately 30% neonatal PV of the newborns.58 In this article, we will discuss the 3 most common outcomes of pemphigus in pregnancy: normal fetal outcome, neonatal pemphigus, and stillbirth.

Normal fetal outcome

Most of the patients with pemphigus can give birth to a normal full-term, healthy newborn through vaginal delivery or cesarean section, depending on the collaborative efforts of the dermatologist and obstetrician.56 In our study, although there were only 7 (33.3%) healthy neonates from the cases with pemphigus diagnosis before pregnancy, we considered it likely to be an underestimate due to the less frequent reports of successful deliveries than that of neonatal adverse outcomes.

Neonatal pemphigus

Neonatal pemphigus is a rarely reported transitory autoimmune blistering disease. It is clinically characterized by transient flaccid blisters and erosions on the skin and rarely on the mucous membranes.17 The disease can be self-healing at 2-3 weeks without special treatment, and does not have long-term clinical significance. No new vesicles or bullae appears in the newborn after birth. Neonatal PV has never been reported to persist beyond the neonatal period and progress to adult disease.17,34,35,39 Neonatal pemphigus is mainly due to the transplacental transmission of antibodies, and only a very small amount of immunoglobulin G (IgG) is synthesized by the neonate itself.36,59 Pemphigus IgG is found both in the fetal circulation and fixed to the fetal epidermis in a characteristic intercellular distribution, while IgA, IgM, IgE, and IgD generally do not participate in the passive transport.60 Contrary to PV, PF in pregnant women rarely leads to neonatal skin lesions.61 The absence of skin disease in the newborns may be due to low transfer of IgG4 autoantibodies through the placenta, and the “immunosorbent” effect of the placenta to contain desmosomes and desmogleins.62-65 This is because to the distribution and cross-compensation of the pemphigus antigens desmoglein 3 and 1 in neonatal and adult skin or mucosa are different.60

Stillbirth

In the literature, the rate of stillbirth in pemphigus during pregnancy was reported to range from 1.4-27%.18,33,56,66 In contrast to the high percentage of some previous observations, pregnancy ended in stillbirth in only one case (4.8%) of pemphigus diagnosed before pregnancy and 2 cases (7.7%) of pemphigus diagnosed during pregnancy in our study. The occurrence of stillbirth emphasizes the management problems encountered when a pemphigus patient becomes pregnant.56,66No relevance has been indicated between maternal treatment regimen and fetal outcome.38,67 Instead of particular medications, adverse pregnancy outcomes seem to be correlated more closely to poor maternal disease control, higher maternal serum, and umbilical cord blood antibody titers.38

Treatment options

Almost all types of pemphigus patients experience severe worsening of the disease after delivery if there is a lack of treatment during pregnancy (n=66). Treatment is often required to control both maternal diseases and fetal outcomes.68 The current study suggested that standard therapy gives priority to systemic glucocorticoids, alone or in combination with other immunosuppressive agents such as immunosuppressant, intravenous immunoglobulin (IVIg) or plasmapheresis.15,32,69 If the disease worsens during the first trimester, a medical termination of pregnancy may be considered, and if it happens during the second and third trimester, application of corticosteroids is a safe treatment.20 The treatment of pemphigus patients diagnosed during pregnancy is similar to the treatment before pregnancy.38

Glucocorticoids

The use of systemic steroids is considered safe in pregnancy, and glucocorticoid remains the first-line agent for treatment with low dosages when patients are mildly ill.70 Some corticosteroids such as prednisone (FDA pregnancy category B), featured with a fast action and high pharmacological effect, can be safely used as immunosuppressive drugs during pregnancy as they do not readily cross the placenta. Prednisone is the safest drug compared with other less used glucocorticoids such as dexamethasone and betamethasone.71,72 The dose of prednisone/prednisolone should be reduced to the lowest effective dose, and standardized doses are still experimental.15,19,32,56

Immunosuppressants

Immunosuppression of steroid-sparing agents are needed when pemphigus has to be controlled by larger doses of medications. Azathioprine is the most widely used steroid-sparing agent for pemphigus.73,74 Cyclosporine is believed to be less effective in the treatment of pemphigus, but it is the safest corticosteroid-sparing agent in pregnancy.38,69 Mycophenolatemofetil, cyclophosphamide, and methotrexate are strongly discouraged or even contraindicated in pregnancy.38,72

Intravenous immunoglobulin

There is moderate evidence suggestive of an effective and safe effect of IVIg as an auxiliary therapy in pregnancy patients with pemphigus.75-77 Therefore, when pregnancy is associated with significant medical problems or disease states, clinicians may need to consider using IVIg early.78

Plasmapheresis

Plasmapheresis is a useful alternative immunosuppressive therapy in pregnancy, which can be used as adjuvant therapy, combined with systemic corticosteroids, reducing the dosage of glucocorticoid treatment.21In conclusion, the patients may suffer from pemphigus before or during pregnancy. The condition of pemphigus and pregnancy can interact with each other and make the treatment and prognosis of these diseases more complicated, presenting challenges for the clinician. Pregnancy may precipitate or aggravate pemphigus, and new born babies of such patients may have a normal outcome or neonatal pemphigus, or, rarely, a stillbirth. Current treatment of pemphigus coexisting with pregnancy priorities systemic glucocorticoids, alone or in combination with other immunosuppressive agents such as immunosuppressants, IVIg or plasmapheresis. The number of reported cases of pemphigus in pregnancy is too small to predict the change of conditions for an individual patient. In summary, pemphigus and pregnancy is still an indistinct area that needs collaborative work by obstetricians, dermatologists, neonatologists, endocrinologists, and oral medicine specialists, to establish a mechanism of multi-disciplinary treatment.     

Sublingual varices in relation to smoking,cardiovascular diseases,denture wearing,and consuming vitamin rich foods

Objectives:

To identify potential risk factors such as smoking, cardiovascular diseases (CVD), denture wearing, and consuming vitamin rich foods, and its relation to the development of sublingual varices (SLV).

Methods:

This cross-sectional observational study was conducted on patients who attended the Department of Dentistry at The University of Jordan Hospital, Amman, Jordan between February and May 2013. Clinical examinations and inspections of 391 patients (203 males and 188 females), 13-74 years of age were conducted to determine the presence of SLV. Sublingual varices were classified into 2 categories: grade 0 (few or none visible), and grade one (moderate or severe). Frequency distributions of both SLV and risk factors were obtained. Multiple logistic regression analysis and Chi-square test were used to analyze the influence of individual risk factors on the incidence of SLV.

Results:

There were 88 subjects (22.5%) who had SLV. In the multivariate logistic regression model, SLV were significantly associated with age (odds ratio [OR]: 2.27, p=0.008) with highest occurrences in the eighth decade of life, gender (OR: 2.74, p=0.001), smoking (OR: 2.93, p=0.002), denture wearing (OR: 2.03, p=0.044), and CVD (OR: 4.01, p=0.00).

Conclusion:

The presence of SLV could be indicative of some potential risk factors including old age, female gender, and denture wearing, and may alert the dental clinician to recognize underlying systemic conditions, particularly CVD.Sublingual varices (SLV) are dilated tortuous veins that may be seen along the ventral surface of the tongue or floor of mouth, and tend to become more prominent with age. However, in a young population, such vascular lesions could be part of Fabry, or Osler syndrome.1 Sublingual varices may be noticed by patients, or more commonly by dentists. They are often confused with the main veins running from the tip of the tongue backwards, and should be differentiated from primary malignant melanomas of the tongue base.1 Several explanations have been suggested concerning the pathogenesis of SLV; it is known that the ageing process, including changes in the connective tissues and venous walls is associated with an increase in the incidence of varices.2-4 Kaplan and Moskona5 reported that varicosities increased from 11.1-41.1% between ages 50-99 years. Few studies in the literature1,2-4,6-10 investigated the relation between SLV and some potential risk factors, such as cardiovascular diseases (CVD), smoking, denture wearing, and consuming foods rich in vitamins, such as vegetables. Furthermore, portal hypertension,6 and varicose veins of the leg2 have been claimed to have a possible connection and association with SLV. Differences in the incidence of SLV between males and females has been the subject of a recent survey.1 The relation between SLV and CVD remains controversial; whereas some studies found no relation,4,6 other older studies reported an association.2,3 A recent study1 of 281 consecutive adults aged 40-92 years demonstrated a strong association between CVD and SLV. Similarly, controversy regarding the relation between SLV and smoking still exists, and there is one study published in the English literature investigating the relation between SLV and smoking.1 Smoking was established as a predisposing factor for CVD, particularly hypertension.11 Hedström and Bergh1 found that SLV was significantly associated with smoking. However, Kroeger et al12 reported a preventive effect of smoking on the development of varicose veins of the leg. Ettinger and Manderson,2 in their study of SLV found a relation between sublingual veins and varicose veins of the leg. Sublingual varices were also ascribed to vitamin C deficiency in older age groups. A study of 22 elderly vegetarians aged 57-75 years found a much lower incidence of sublingual petechiae and varicosities than generally reported in an older population.7 However, the literature did not support a link between SLV and diabetes,13 or denture wear.8-10 In Jordan, a recent study showed that more than 48% of adult males were current smokers.14 In addition, more than 60% of patients who attended the United Nations Relief and Works Agency (UNRWA) primary health care clinics in Jordan were diagnosed with hypertension.15 Hence, it is expected that SLV could be a common finding among a Jordanian population. Therefore, the aim of this study was to assess the influence of potential risk factors including CVD, smoking, denture wearing, and consuming vitamin rich foods on the incidence of SLV among the young, middle aged, and elderly population.     

Effects of occupational therapy on quality of life of patients with metastatic prostate cancer: A randomized controlled study

Objectives:

To evaluate the efficiency of occupational therapy relative to a home program in improving quality of life (QoL) among men who were treated for metastatic prostate cancer (MPC).

Methods:

Fifty-five men were assigned randomly to either the 12-week cognitive behavioral therapy based occupational therapy (OT-CBSM) intervention (treatment group) or a home program (control group) between March 2012 and August 2014 in the Department of Occupational Therapy, Faculty of Health Sciences, Hacettepe University, Ankara, Turkey. The Canadian Occupational Performance Measure (COPM) was used to measure the occupational performance and identify difficulties in daily living activities. The QoL and symptom status were measured by The European Organization for Research and Treatment of Cancer Core Quality of Life Questionnaire C30 and its Prostate Cancer Module. A 12-week OT-CBSM intervention including client-centered training of daily living activities, recreational group activities, and cognitive behavioral stress management intervention were applied.

Results:

The COPM performance and satisfaction scores, which indicate occupational participation and QoL increased statistically in the treatment group in relation to men who were included in the home-program (p≤0.05).

Conclusion:

A 12-week OT-CBSM intervention was effective in improving QoL in men treated for MPC, and these changes were associated significantly with occupational performance.Prostate cancer is one of the most frequent male malignancies in the world.1 The development of serum prostate-specific antigen (PSA) and advanced prostate cancer treatment modalities increased 10-year survival rates from ~60% to >70%.2 Prostate cancer can be occurred as a local disease or advanced metastatic disease. The standard of care for metastatic prostate cancer (MPC) is hormone (androgen blockade) therapy, which delays progression and relieves pain for an average of 18 months to 24 months.3,4 Nearly all patients who have hormone therapy eventually develop significant disease and treatment related morbidity including fatigue, decrease in bone density, bone pain, weight loss, gynecomastia, and hot flushes.3 Increased survival and subsequent functional, physical, and psychological needs produced a growing acceptance of understanding the rehabilitation needs to increase the occupational performance and quality of life (QoL) of the patients with MPC.5 Occupational therapy (OT), one of the core elements of oncologic rehabilitation, is in a unique position to contribute to the development and fulfillment of occupational performance and participation with the motto of ‘live life to its fullest’.6 The role of the occupational therapist in oncology is to facilitate and enable an individual to achieve maximum functional performance, both physically and psychologically, in everyday living skills regardless of his or her life expectancy.6 Occupational performance or participation in everyday occupations is vital for all humans as defined by the International Classification of Functioning, Disability and Health7 (ICF). Occupational performance has a positive influence on health, well-being, and the presence of cancer has been found to lead to participation in meaningful activities /occupations that are effected by the cancer and its treatments.8 Previous studies9-14 have ably identified OT interventions mostly in general oncology and palliative care. The literature on OT, specifically on patients with breast cancer, investigates management of pain, fatigue, nausea, metastatic patients intervention, stress reducing and management program, the value of engagement in meaningful activities, lymphedema, vocational rehabilitation, creative and therapeutic use of activity, cognitive therapy, and, changing life style with cognitive behavioral therapy.9-14 According to the literature, a survey on women with breast cancer provides a picture of the interventions employed by the occupational therapists and can help to create an OT service to regain the patients level of control and independence by maintaining or resuming engagement in purposeful occupations and meaningful activities; however, the effect of OT in patients’ QoL was not completely specified.15,16 Another interdisciplinary study recommended examination of the effectiveness of OT in patients’ functional needs and to promote evidence-based practice of OT in oncology.8,17Prostate cancer oriented rehabilitation interventions may be valuable in functioning, and activity participation in daily living activities and also in helping men to acknowledge, express, accept, and use a problem solving approach on the changes that occur as a result of treatment and to seek out adaptive solutions for enduring fatigue, bone pain, weight loss, gynecomastia, and hot flushes.18 Such interventions may lead to significant improvements in functional, cognitive, and emotional coping skills, use of social support, utilization of health care, and management of symptoms.5,18-21 Rehabilitation interventions were adapted to meet the needs of cancer patients including functional individualized support and group therapy interventions22 and stress management intervention23 approaches. The research shows that effective stress management components include relaxation training to lower arousal, disease information and management, an emotionally supportive environment in which participants can address fears and anxieties, behavioral and cognitive coping strategies, and social support.19,20 Participation in rehabilitation intervention provides a clear and robust benefit to cancer patients by relieving treatment-related symptoms, reducing the physiologic concomitants of stress, and improving mood. Previous study19 found that the benefits in coping with cancer may be quite significant in male participants.19 This is supported by the positive experiences that men report from their participation in rehabilitation programs. Although, collectively, these findings indicated that men treated for prostate cancer derive benefit from a rehabilitation experience, most studies did not include a randomized intervention design and did not study the occupational performance of the participants.15,23 Only a few studies20,21 have investigated the efficacy of structured stress-management interventions in improving QoL and the mechanisms associated with such improvements despite stressful and negative side effects associated with treatment with limited activity participation.The limited reports in the literature indicates that there is a lack of study on the effect of OT combined cognitive behavioral stress management skills in patients with MPC. In the current study, it was hypothesized that participants treated for MPC enrolled in the cognitive behavioral stress management based OT (OT-CBSM) would demonstrate greater improvements in occupational performance and QoL compared with a control group (CG) enrolled in the home-program. The objectives of this study were to identify the effect of OT-CBSM on occupational participation and QoL, and to explore the areas/activities of daily life that were the most commonly affected, and needed support in patients with MPC.     

Pattern of drugs use and association with anti-mutated citrullinated vimentin antibody in rheumatoid arthritis

Objectives:

To demonstrate the pattern of disease-modifying antirheumatic drugs (DMARDs) use in Saudi and non-Saudi rheumatoid arthritis (RA) patients, and to evaluate the association of DMARDs use with anti-mutated citrullinated vimentin (anti-MCV) positivity and other factors.

Methods:

Retrospectively, for a period of 7 years (2007-2014), we studied 205 RA patients, at King Abdulaziz University Hospital (KAUH), Jeddah, Saudi Arabia. All patients used DMARDs. Pattern of use for all 6 DMARDs was almost the same among Saudis and non-Saudis with no significant difference (p>0.05) for each DMARD; MTX was the most commonly used DMARD (71-76%).

Results:

There was no association between anti-MCV positivity and different DMARDs use. Methotrexate was used 76 times as combination, scoring the highest in this respect. There was a significant correlation (p<0.05) between Plaquenil with Methotrexate and with Sulfasalazine; Leflunomide with anti-TNF and with Prednisolone; age with Methotrexate and with Plaquenil; anti-MCV positivity with Prednisolone. Saudi/non-Saudi status showed no correlation with all factors or drugs. There was no significant association between DMARDs and comorbidity.

Conclusion:

Similar to worldwide results, MTX was the most commonly used DMARD; with the addition of anti-TNF to increase the effect, and folic acid to minimize the side effects. In this cohort, the pattern of use for all DMARDs was similar among Saudis and non-Saudis; treatment depended neither on anti-MCV positivity nor on the presence of comorbid conditions. A study of the association of DMARDs with disease activity is recommended.The effective treatment of rheumatoid arthritis (RA) can be achieved by disease-modifying antirheumatic drugs (DMARDs) that decrease joint damage with improvement of symptoms and functional abilities.1 The DMARDs have been classified into synthetic (sDMARDs) and biological.2 The sDMARDs are traditional drugs; such as methotrexate (MTX), sulfasalazine, leflunomide, and hydroxychloroquine (Plaquenil).2 The sDMARDs also include synthetic glucocorticoids (such as Prednisolone).3 If an sDMARDs is not effective after a trial of 3 months,4 they are usually combined with a biological DMARD, such as tumor necrosis factor alpha (TNF-α) blockers.1 To achieve disease remission in approximately 50 of people and improved overall outcomes, the DMARDs should be started very early in the disease.5 The frequently used DMARDs include MTX (the most commonly used one), Plaquenil (hydroxychloroquine), Azulfidine (sulfasalazine), and Arava (leflunomide), either as monotherapy, or in combination.1 Methotrexate is the most commonly used DMARD wordwide,6,7 and is the first line of treatment;8-10 even according to the treatment guidelines from the American College of Rheumatology (2012),11 and the European League Against Rheumatism (2010).12 Methotrexate is usually combined with folic acid (a vitamin),13 in order to reduce its adverse effects including nausea, vomiting or abdominal pain (gastrointestinal), hematologic, pulmonary, and hepatic.10 Methotrexate is teratogenic, thus, pregnancy should be avoided.8,10 Prednisolone (a synthetic glucocorticoids) can be used in the short term, while waiting for slow-onset drugs to take effect,1 and also as an injections into individual joints.1 Although its long-term use reduces joint damage, it also results in osteoporosis and susceptibility to infections, and thus is not recommended.1 A better effect can be achieved by combining MTX with anti-TNF than with MTX monotherapy.14 The response rate is better when switching from MTX monotherapy to MTX plus anti-TNF than combined DMARDs to MTX plus anti-TNF.14 In this study, our aim was to determine the pattern of disease modifying antirheumatic drugs use, and their association with anti-mutated citrullinated vimentin antibody (anti-MCV) in rheumatoid arthritis patients.     

Prevalence and severity of plaque-induced gingivitis in a Saudi adult population

Objectives:

To evaluate the prevalence and severity of plaque-induced gingivitis among a Saudi adult population in Riyadh region.

Methods:

Three hundred and eighty-five eligible participants in this cross-sectional study were recruited from routine dental patients attending the oral diagnosis clinic at Al-Farabi College in Riyadh, Saudi Arabia from June 2013 to December 2013. A clinical examination was performed by 2 dentists to measure the gingival and plaque indices of Löe and Silness for each participant.

Results:

The prevalence of gingivitis was 100% among adult subjects aged between 18-40 years old. Moreover, the mean gingival index was 1.68±0.31, which indicates a moderate gingival inflammation. In fact, males showed more severe signs of gingival inflammation compared with females (p=0.001). In addition, the mean plaque index was 0.875±0.49, which indicates a good plaque status of the participants. Interestingly, the age was not related either to the gingival inflammation (p=0.13), or to the amount of plaque accumulation (p=0.17). However, males were more affected than females (p=0.005).

Conclusion:

The results of this study show that plaque accumulation is strongly associated with high prevalence of moderate to severe gingivitis among Saudi subjects.Plaque-induced gingivitis is the most common form of periodontal disease,1 which is considered to be the second most common oral disease after dental caries, affecting more than 75% of the population worldwide.2,3 In 2000, the United States Surgeon General released a report calling interest to the ‘‘silent epidemic’’ of dental and oral diseases, mainly dental caries and periodontal diseases suffered by millions of people throughout the US.4 The prevalence of periodontal diseases varies in different studies and different countries as a result of variations in study populations, age of participants, and the procedure of defining and diagnosing this type of disease. In general, gingivitis begins in early childhood, and becomes more prevalent and severe with age.5,6 Epidemiological studies revealed that plaque-induced gingivitis is prevalent among all ages of dentate individuals.7-9 Plaque-induced gingivitis is characterized by the presence of inflammation confined to gingiva without extension into other tooth-supporting structures.10-12 Persistence of this type of inflammation is correlated with the presence of microbial dental plaque. As long as this microbial biofilm is present adjacent to the gingival tissues, the inflammation will not resolve.13 However, it has been shown to be reversible after removing these causative factors.14 The clinical features that can be used as characteristic of gingivitis could be one of the following signs: erythematic and sponginess; changes in contour; bleeding upon stimulation; and presence of calculus, or plaque without clinical attachment loss, or radiographic evidence of crestal bone loss.15 Clinically, the severity and signs of gingival inflammation can be expressed by means of gingival index (GI) of Löe and Silness.16 According to this index, gingival inflammation can be classified as mild, moderate, or severe. However, the presence of these signs of inflammation is considered the initial stage for the more severe and irreversible form of periodontal diseases.17-19 A patient''s susceptibility to develop this type of disease also is highly variable and depends on the host response towards periodontal pathogens,17-19 which may be influenced by both acquired and genetic factors that can modify this susceptibility to infection.12,20 Prevention of dental plaque accumulation and early treatment of gingivitis reduces the risks associated with the development of a more severe, and destructive form of periodontal diseases.11,21 It is well known and documented that gingivitis develops after 10-21 days of accumulation of dental plaque,22 necessitating a daily effort to prevent plaque accumulation. Several studies revealed a significant correlation between reducing the incidence of gingivitis and regular plaque control measures.23-25 The aim of this study was to evaluate the prevalence and severity of plaque-induced gingivitis among a Saudi adult population in Riyadh region.     

The variations of peroneus digiti quinti muscle and its contribution to the extension of the fifth toe: A cadaveric study

Objectives:

To investigate the origin, prevalence, and possible effects of peroneus digiti quinti muscle (PDQ) on the fifth toe, to find out the variations of PDQ by determining the relationship between peroneus brevis muscle (PB) and PDQ, and to reveal its importance for the applications in foot and ankle surgery.

Methods:

This study was conducted at the Faculty of Medicine, Kahramanmaras Sutcu Imam University, Kahramanmaras, Turkey between September 2013 and June 2014. The study was a prospective dissection of cadaveric lower limbs. Twenty-five amputated lower limbs were stored in the freezer at -15°C. The legs were dissected; prevalence and variations of peroneus digiti quinti were investigated.

Results:

Peroneus digiti quinti muscle was found in 8 (32%) of 25 dissected lower limbs. However, 2 different tendon extensions were found at 3 (37.5%) of 8, and 5 (62.5%) of them were determined to have a single tendon.

Conclusion:

The incidence, dimensions, length, and insertions of peroneus digiti quinti are important in the evaluation and treatment of functional loss of the fifth toe, lateral foot deformities, and tendon problems behind the lateral malleolus of the ankle.There are 2 peroneal muscles in the lateral compartment of the leg. Peroneus longus muscle (PL) is longer than the 2, passing behind the lateral malleolus (LM), and enters a groove under the cuboid bone and reaches its attachment at the base of first metatarsal bone. Peroneus brevis muscle (PB) is the shorter one, passing behind LM, and attaches the tuberosity of the fifth metatarsal bone.1,2 However, due to developmental factors, it is claimed that the variations, or rather accessory tendons of these muscles are quite common.3 Variationally, there may be various accessory tendons, the incidence of which changes from one population to another, such as peroneus tertius muscle (PT), and peroneus digiti quinti muscle (PDQ), and particularly peroneus quartus muscle (PQ).4-7 Generally, these muscles arise from peroneus brevis but their insertions exhibit variabilities.8 Peroneus quartus muscle inserts on the calcaneus and adjacent structures,9 PT inserts on the base of the fifth metatarsal bone10 and PDQ inserts on the fifth toe.3 The presence of PQ was reported to be approximately 22%,11-13 and PT to be approximately 10%.10 The prevalence of PDQ is so varied in the literature that it was reported by Reimann14 as 79.5%, and by Jadhav et al15 as 51%. Peroneus digiti quinti muscle extends as a small slip from the tendon of PB to the extensor aponeurosis,15,16 or proximal phalanx of the fifth toe.6 Peroneus digiti quinti muscle is innervated by superficial fibular nerve just like PB.17,18 Moreover, in some studies, it is stated that PDQ is innervated by the accessory deep peroneal nerve.18 Generally it is reported that PDQ, the diameter of which varies from 0.7 to 3 mm, does not have any kind of function since it has a really small muscle belly and a thin tendon.14 Generally, accessory muscles are asymptomatic, and they can lead different clinical symptoms related to vessels, nerves, and tendons.17,19 Peroneus digiti quinti muscle is also an asymptomatic accessory muscle, which means that it does not cause any pain, or neurological disorder.15 In a study carried out by Macalister,25 Yammine stated that in cases that PQ developed fully, PDQ arose from PQ, and reached the fifth proximal phalanx and contributed to the extension of the fifth toe.3 According to some other articles,6,15 PDQ is usually separated from PB, and there is insufficient information regarding its function. It has been only stated that PDQ partially pronates the fifth toe.20 Loss of function can be observed at muscle-tendon units of toes due to traumatic or non-traumatic reasons, and the muscle-tendon units can lose their primary functions. Tendon anomalies may confuse the clinicians during evaluation of their functions. In order to evaluate the function and anatomic structure of the foot, it is necessary to know the function, morphology of the muscles and tendons, as well as their anomalies. Peroneus digiti quinti muscle, when present, can be used as an accessory muscle and it can contribute to the extension of the fifth toe, since it ends on the dorsal aponeurosis of the fifth toe. Therefore, the aim of this study was to: 1) investigate the origin, prevalence, and possible effect of PDQ on the fifth toe, 2) to find out the variations of PDQ by determining the relationship between PB and PDQ, and 3) to reveal its importance for the applications in foot and ankle surgery.     

The desire to utilize postmastectomy breast reconstruction in Saudi Arabian women: Predictors and barriers

Objectives:

To study factors that influence the desire to utilize breast reconstruction after mastectomy, and to investigate the barriers to reconstruction among women in Saudi Arabia.

Methods:

We conducted a cross-sectional study at 2 surgical centers in Jeddah, Saudi Arabia. A self-administered questionnaire was distributed to all breast cancer patients attending the surgery clinics for follow-up after mastectomy between January and March 2013. Ninety-one patients met the study inclusion criteria. The first part of the questionnaire covered the demographic and socioeconomic information regarding factors that might influence the desire to utilize breast reconstruction including possible barriers. Multivariate logistic regression was used to determine the significant predictors of the desire to undergo reconstruction.

Results:

Overall, 16.5% of patients underwent breast reconstruction after mastectomy. Young age and high educational attainment were significantly associated with an increased desire to undergo reconstruction. The main barriers to reconstruction were the lack of adequate information on the procedure (63%), concerns on the complications of the procedure (68%), and concerns on the reconstruction interfering with the detection of recurrence (54%).

Conclusion:

Age and educational level were significant predictors of the desire to utilize breast reconstruction. Furthermore, modifiable barriers included the lack of knowledge and misconceptions on the procedure. Addressing these issues may increase the rate of breast reconstruction in Saudi Arabia.Surgical resection (mastectomy) is considered the primary treatment for breast cancer. In the past decade, changing attitudes toward breast reconstruction among both patients and providers have led to an increasing number of women seeking breast reconstruction after mastectomy.1 In 2009, there were approximately 86,000 breast reconstruction procedures performed in the United States.2 There has been a significant rise in immediate reconstruction rates, attributable to a notable increase in implant use.3 Many types of breast reconstruction are available including silicone and silane implants, tissue expanders, and pedicle and free musculocutaneous flaps.4,5 Although these reconstruction options have been proven to be oncologically safe,5 and many women still refuse breast reconstruction.6 The choice to proceed with breast reconstruction after mastectomy is difficult, and is affected by many factors. Most breast reconstruction procedures are performed in women younger than 60 years of age.7 The decision to proceed with reconstruction can be influenced by patient factors, physician factors, cancer related factors, and insurance status.7-10 Patient factors include patient age, socioeconomic status, race, site of mastectomy, and patient preference.1 Of these factors, age >50 years is the most common negative predictor of breast reconstruction after mastectomy.8,9,11-13 According to the Saudi Cancer Registry,14 breast cancer has been the most common cancer among Saudi females over the past 12 years. In a recent study, Ibrahim et al15 estimated that the burden of breast cancer in Saudi Arabia will increase by approximately 350% by 2025. In a previously published study, almost half of the general surgeons surveyed reported that they had treated patients who refused breast reconstruction despite its availability.4 Previous studies on the factors influencing postmastectomy breast reconstruction in the Middle East were conducted in Egypt13,14 and we are not aware of any similar studies conducted in Saudi Arabia or the Gulf Region. The objectives of this exploratory study were to study the demographic and socioeconomic factors influencing the desire to utilize postmastectomy breast reconstruction and to evaluate the barriers to postmastectomy breast reconstruction among women in Saudi Arabia.     

Adherence to the American Diabetes Association standards of care among patients with type 2 diabetes in primary care in Saudi Arabia

Objectives:

To assess adherence to 11 American Diabetes Association (ADA) standards of diabetic care.

Methods:

We conducted this one-year historical prospective study between October 2010 and September 2011 on 450 adult type 2 diabetes patients in a primary care center in Saudi Arabia. We used the definitions of the 2010 ADA standards of diabetic care processes and targets.

Results:

Four-hundred and fifty medical files were valid. The adherence to ADA process standards of measurement of glycated hemoglobin (HbA1c) was 68.7%, 92.9% for blood pressure, and 80.2% for serum lipids. Screening was lowest for nephropathy (35.6%), and highest for diabetic foot (72%). Adherence to medications ranged between 82.2% for antiplatelets, and 92.4% for dyslipidemia. For outcome standards, 24.2% of the patients had an HbA1c <7%, and 32.2% had controlled blood pressure (<130/80 mm Hg); and 58.5% achieved targeted low-density lipoproteins (LDL). Only 7.2% had glycemic control in addition to controlled blood pressure and targeted LDL level. An increasing trend of patients achieving glycemic control (<7%) was shown throughout follow-up (p=0.003).

Conclusions:

We found suboptimal adherence with many ADA standards of diabetic care among patients with type 2 diabetes treated at a primary care center in Saudi Arabia. The achievement of outcome standards, either singly or combined, is lower than the adherence rates. However, the figures show improvement in adherence during the follow-up period.Diabetes mellitus is a chronic disease that can cause devastating secondary complications, reducing the quality and length of life as well as increasing medical costs for the patient and society.1-3 Saudi Arabia has one of the highest diabetes prevalence rates worldwide. The International Diabetes Federation estimates that 8.3% of the world’s adult population (20-79 years) have diabetes, with Saudi Arabia one of the top countries affected (20%).4 Additionally, a national study estimated the overall prevalence of diabetes in Saudis aged 30-70 years at 23.7% (26.7% in women, and 21.5% in men).5Diabetes care is a complex process requiring ongoing patient self-management, education, and support to prevent acute complications, and to reduce the risk of long-term complications.6 Compelling evidence from clinical trials shows that intensive glycemic control effectively delays the onset and slows the progression of diabetic complications, such as nephropathy, retinopathy, and neuropathy.7-9 Likewise, substantial evidence shows that control of associated risk factors such as hypertension and dyslipidemia is protective against undesirable outcomes in patients with diabetes.10-14 The American Diabetes Association (ADA) put together a set of diabetic care standards that are annually revised.15 However, despite the availability of convincing evidence and clear guidelines, many studies throughout the world reported suboptimal adherence to diabetic care standards.16-19 Only a few studies have examined the quality of diabetic care among Saudi patients in a primary care setting,20 outpatient clinics of internal medicine,21,22 and specialized diabetic care centers.23 These studies covered one or more of the screening, diagnostic, and therapeutic components of the ADA standards of diabetic care. However, the extent to which these standards are met at primary care settings was not comprehensively studied. Moreover, the degree to which multiple ADA processes and outcomes are simultaneously achieved was also not studied. Therefore, we aimed to assess the adherence of primary care patients to 11 ADA standards of diabetic care including glycemic control, blood pressure control, and lipid management, singly and combined.     

Recognition of oxidized albumin and thyroid antigens by psoriasis autoantibodies: A possible role of reactive-oxygen-species induced epitopes in chronic plaque psoriasis

Objectives:

To investigate the role of reactive-oxygen-species (ROS) induced epitopes on human-serum-albumin (HSA) and thyroid antigens in psoriasis autoimmunity.

Methods:

This study was performed in the College of Medicine, Qassim University, Buraidah, Saudi Arabia between May 2014 and February 2015. The study was designed to explore the role of ROS-induced epitopes in psoriasis autoimmunity. Singlet-oxygen (or ROS)-induced epitopes on protein (ROS-epitopes-albumin) was characterized by in-vitro and in-vivo. Thyroid antigens were prepared from rabbit thyroid, and thyroglobulin was isolated from thyroid extract. Immunocross-reactions of protein-A purified anti-ROS-epitopes-HSA-immunoglobulin G (IgGs) with thyroid antigen, thyroglobulin, and their oxidized forms were determined. Binding characteristics of autoantibodies in chronic plaque psoriasis patients (n=26) against ROS-epitopes-HSA and also with native and oxidized thyroid antigens were screened, and the results were compared with age-matched controls (n=22).

Results:

The anti-ROS-epitopes-HSA-IgGs showed cross-reactions with thyroid antigen, thyroglobulin and with their oxidized forms. High degree of specific binding by psoriasis IgGs to ROS-epitopes-HSA, ROS-thyroid antigen and ROS-thyroglobulin was observed. Immunoglobulin G from normal-human-controls showed negligible binding with all tested antigens. Moreover, sera from psoriasis patients had higher levels of carbonyl contents compared with control sera.

Conclusion:

Structural alterations in albumin, thyroid antigens by ROS, generate unique neo-epitopes that might be one of the factors for the induction of autoantibodies in psoriasis.Psoriasis, a chronic skin disorder is known to be the most prevalent autoimmune disorder in humans.1 It is characterized by hyperplasia of the epidermis, infiltration of leukocytes of dermis and epidermis as well as dilatation and proliferation of blood vessels, which are likely to be triggered by multiple factors such as drugs, physical and psychological stress, bacterial infections, or injury.2 Psoriasis appears in different clinical variants and the most frequently is the plaque psoriasis (also known as psoriasis vulgaris), presents with scaly red plaques on common areas, such as on scalp, the back, dorsal skin of the elbows, and ventral skin of knees.3 Although, the role of immunologic and environmental factors in the pathogenesis of plaques psoriasis has been proposed, but the precise etiology of disease remains poorly understood.1,3 It is well documented that oxidative stress is one of the major factors involved in the pathogenesis of psoriasis4-6 and now it has been well established that excess generation of reactive oxygen species (ROS) by the immune system play a vital role in the development of psoriasis.7 Cellular events such as cell proliferation, apoptosis, cell differentiation, and immune response are influenced by ROS, and these events are altered in psoriasis patients.4-7 Although the exact pathogenesis of psoriasis is unknown, but the occurrence of autoimmune reactions has been assumed,8-10 the presence of autoantibodies and various underlying immunologic abnormalities in the affected sites of these patients have also been reported.8,11-15 The autoimmune etiology has been also proposed on the basis of its association with various autoimmune diseases,8,10 but the precise mechanism of generation of autoantibodies in psoriasis remains unclear.Thyroid disorders have a high prevalence in medical practice; they are associated with a wide range of diseases with which they may or may not share etiological factors. One of the organs which best show this wide range of clinical signs of thyroid dysfunctions is the skin.16-18 Thyroid abnormalities are well documented in psoriasis patients, thyroid gland causes an increase of epidermal growth factor levels, which has an important role in keratinocytes proliferation in psoriasis.19-21 In addition, a high prevalence of thyroid associated autoimmunity has also been reported in patients with psoriasis.20 Moreover, elevated ROS levels are often seen to be associated with thyroid dysfunctions, and now it is proposed that the thyroid hormones influence the ROS steady-state environment in the cell.22-24 The most common idea is the hyperthyroidism, which enhances the ROS production that perturbs the ROS steady-state environment to facilitate the cellular damage or damage to the cellular components as also reported in psoriasis patients.22,25 Therefore, it is assumed that in psoriasis, cells or cellular components are continuously exposed to oxidative stress, so that alterations in conformation and function of these cellular components may occur, which may results in modification of their biological properties. In view of these, this study was aimed to investigate the role of ROS-induced epitopes on albumin and thyroid antigens in psoriasis autoimmunity. To test this, ROS-modified epitopes were generated on albumin and antibodies against ROS-modified-albumin (anti-ROS-modified-epitopes antibodies) were experimentally generated. Cross-reactions of affinity purified anti-ROS-modified-epitopes immunoglobulin Gs (IgGs) with native- and ROS- modified thyroid antigen, thyroglobulin or human DNA were determined. Our data showed that anti-ROS-modified-epitopes-IgGs showed immunospecificity with thyroid antigen, thyroglobulin and with their oxidized forms. Importantly, the antigen(s) binding characteristics of naturally occurring chronic plaque psoriasis antibodies to ROS-modified epitopes, thyroid antigen, ROS-modified thyroid antigen, thyroglobulin, ROS-modified thyroglobulin, human DNA, and ROS-modified human DNA were determined.     

Familial aggregation and excess maternal transmission of type 2 diabetes in Tunisia

Aim

To evaluate the degree of familial aggregation of type 2 diabetes mellitus in Tunisia and to investigate transmission patterns of the disease and their relationships with patients'' clinical profiles.

Methods

Family history of diabetes and clinical data were collected for 132 unrelated type 2 diabetic Tunisian patients. Diabetes status was recorded for first degree relatives (parents, siblings) and second degree relatives (aunts and uncles from both maternal and paternal sides). Information about family history of diabetes was gathered for a total of 1767 individuals.

Results

Familial aggregation of type 2 diabetes was prominent and more important among first degree relatives than among second degree relatives (p = 0.01). Among studied subjects, 70% reported at least one relative with diabetes and 34% had at least one parent with diabetes. Diabetes was more frequent among mothers than fathers of probands (p = 0.03). This maternal effect extends to second degree relatives as diabetes was more common among maternal than paternal aunts and uncles (p = 0.01). There is no significant difference in clinical and metabolic profiles between patients according to transmission patterns of the disease.

Conclusion

These results suggest familial aggregation and excess maternal transmission of type 2 diabetes in the Tunisian studied population.Type 2 diabetes mellitus (T2D) is a common metabolic disorder, characterised by hyperglycaemia caused by impaired glucose homeostasis, and represents a serious public health problem in many developed countries. The prevalence of T2D is increasing at the global level with large variation from one population to another depending on the ethnic origin.^1,2 In Tunisia, like in other developing countries, there is a growing concern for the important socioeconomic impact of the disease—high medical costs and altered quality of life.^3,4 T2D is a multifactorial syndrome depending on complex interactions between environmental and genetic factors. It has been widely reported that the occurrence of T2D is triggered by a genetic susceptibility, as indicated by monozygous twin studies⁵ and familial aggregation in several populations.^6,7,8 Despite recent advances in defining the molecular basis of T2D, the mode of inheritance of this disease is still debated. Several studies have shown that individuals with maternal history of diabetes are at a higher risk of developing the disease than individuals with a paternal diabetes history. The majority of these studies were performed on Europeans, Asians, Americans, and Africans (black South Africans).^7,9,10,11,12 To our knowledge, no studies on familial aggregation of T2D and transmission patterns of the disease in North Africans have been reported. Our aim is to estimate the degree of familial aggregation of T2D in the Tunisian population and to investigate transmission patterns of this disorder and their relationships with patients'' clinical characteristics.     

Evaluation of adjunctive systemic doxycycline with non-surgical periodontal therapy within type 2 diabetic patients

Objectives:

To evaluate the effects of systemic doxycycline on clinical and microbiological parameters of diabetic subjects with chronic periodontitis.

Methods:

This 9-month multi-center, randomized, parallel, single-blinded study was conducted from different hospitals in Riyadh, Saudi Arabia between April 2010 and December 2010. A total of 76 diabetic subjects with chronic periodontitis were randomized into 2 groups: control group (CG) received only scaling and root planing (SRP), and the treatment group (TG) receiving systemic doxycycline during the reevaluation visit 45 days after the completion of SRP. Probing pocket depth, clinical attachment level, gingival index, plaque index, and bleeding on probing were collected at baseline, 45 days after SRP, and one, 3, and 6 months after the use of systemic doxycycline. Microbiological analysis comprised the detection of Tannerella forsythia (Tf), Aggregatibacter actinomycetemcomitans (Aa), Porphyromonas gingivalis (Pg), and Prevotella intermedia (Pi) by polymerase chain reaction method.

Results:

Sixty-eight (33 CG and 35 TG) subjects completed the study. Greater reduction in the population of Tf, Pg, and Pi were observed in TG compared with CG in the first month after the administration of systemic doxycycline. The TG showed a significant improvement in gingival index scores compared with the CG (p<0.05) by the end of the first and 6 months after the administration of doxycycline.

Conclusion:

Adjunct systemic doxycycline can be associated with a reduction of Tf, Pg, and Pi in the first month after the administration of doxycycline with an improvement in the GI.The relationship between periodontal diseases (PD) and diabetes are bidirectional,1 which provides an example of systemic disease predisposing to oral infection, established infection, and exacerbating the systemic disease.2 Diabetic patients are known to be susceptible to infectious diseases.3 The influence of diabetes on the onset and development of PD has been widely studied.4,5 The PD is now considered the sixth complication of diabetes mellitus.6,7 Diabetes in itself does not cause PD, but it makes the patients more susceptible to periodontal destruction. Diabetics exhibit greater severity and a faster rate of PD progression.8,9 Treating chronic periodontitis in diabetic patients poses numerous challenges, especially with regards to the control of oral microorganisms. Treatment of PD is directed to the elimination of sub-gingival bacterial infections. More than 700 different bacterial species are found in the sub-gingival environment.10 Several studies have reported that the bacteria involved in periodontitis are usually anaerobic Gram-negative bacteria.11 Aggregatibacter actinomycetemcomitans (Aa), Tannerella forsythia (Tf), and Porphyromonas gingivalis (Pg) were directly implicated in the destruction of periodontal tissues, and the presence of any of these pathogens is considered a risk factor for future periodontal destruction.12 Direct and indirect damage to periodontal supporting tissues are well-documented pathogenic effects of Gram-negative bacteria due to their toxic products and the activation of a series of inflammatory reactions.13 Mechanical means using non-surgical and surgical techniques is the primary approach employed in the treatment of PD. Subgingival scaling and root planning (SRP) is an effective method to slow or arrest the progression of PD.14,15 Even after meticulous SRP, some patients may still experience continuous loss of attachment due to the inability of the therapy to suppress periodontal pathogens to the optimal levels.16 The Aa and Pg, is likely to evade SRP, especially in the subgingival niche, due to limited access to the root surface and the tissue-invading skills of the bacteria.17 The efficacy of SRP may also be compromised by the remaining bacterial virulence factors and ineffective personal plaque control.18 Thus, various pharmacological agents were used as adjunctive therapy to improve the treatment outcome of non-surgical periodontal therapy.19 Adjunctive antimicrobials can be used for local or systemic delivery. The benefits of using various adjunctive antibiotics such as penicillin, tetracycline, amoxicillin, and metronidazole along with SRP have been reported to improve periodontal health.20-22 Studies that evaluated the antimicrobial effect of systemic doxycycline on the periodontal tissues of diabetic patients are scarce. This study aims to investigate the effect of SRP in conjunction with the administration of an antimicrobial dose of systemic doxycycline on the clinical and microbiological parameters in diabetic patients with chronic periodontitis.     

Favorable therapeutic response of osteoporosis patients to treatment with intravenous zoledronate compared with oral alendronate

Objectives:

To evaluate the efficacy of orally-administered alendronate compared with intravenously-administered zoledronate.

Methods:

This prospective study was carried out at Barts Health HNS Trust between April 2010 and March 2012. This study compares changes in bone mineral density (BMD) in 234 patients treated with 2 bisphosphonates: alendronate taken orally, and zoledronate administered intravenously. One hundred and eighteen patients received alendronate at 70 mg/week, while 116 patients received zoledronate once annually. Dual energy x-ray absorptiometry was used to measure BMD of the left hip and anterior-posterior spine (lumbar L1-L4) skeletal sites at baseline, and at one-, and 2-years post-treatment.

Results:

This study provides evidence that lumbar spine BMD increased by 3.6% in patients receiving alendronate, and 5.7% in patients receiving zoledronate after 2 years compared with baseline values (p=0.0001 for both). Total hip BMD decreased in patients treated with alendronate by 0.4% but increased in patients receiving zoledronate by 0.8% (p=0.0001).

Conclusion:

This study provides evidence that zoledronate is more effective than alendronate in treating patients with osteoporosis and with no gastrointestinal (GI) serious side effects. Furthermore, zoledronate appears to have the added advantage of a better safety profile in patients suffering from GI intolerance of oral bisphosphonates.Osteoporosis is a disease characterized by low bone mass and micro-architectural deterioration of associated tissue.1,2 It is estimated that over 200 million people worldwide have the disease,3 and suffer clinical consequences, including increased incidence of bone fractures, morbidity, and premature mortality.2,3 Approximately 30% of all post-menopausal women suffer from osteoporosis.3 The importance of developing treatment strategies that reduce the risk of fracture is therefore, evident both from individual and societal perspectives. Treatment with nitrogen-containing bisphosphonates, a class of potent therapeutic agents that inhibit osteoclast-mediated bone resorption, is one of the major pharmacological interventions for osteoporosis.4-8 The primary therapeutic goal of treatment with bisphosphonates is to reduce fracture risks.9 In placebo-controlled clinical trials, the efficacy of bisphosphonates in improving bone mineral density (BMD) at key skeletal sites, particularly at the lumbar spine has been demonstrated.10-12 When compared with placebo, all bisphosphonate formula at different dose levels, routes, and frequency of administration significantly increased BMD. In 2012, the Agency for Healthcare Research and Quality (AHRQ) published an update following a systematic review of the comparative effectiveness of treatments for osteoporosis.13 The AHRQ report provided evidence for decreased risk of hip and other non-vertebral fractures in alendronate-, risedronate- and zoledronate-treated patients even in high-risk post-menopausal women.13 As pharmaceutical agents, however, bisphosphonates can cause a number of adverse events, including some that are attributed to mode of administration. For example, gastrointestinal (GI) complaints, such as dysphagia, esophagitis, and esophageal and gastric ulcers are seen predominantly with orally-administered bisphosphonates, such as alendronate, risedronate, and ibandronate.7,8,14-18 In randomized clinical trials of alendronate involving large cohorts of patients, high incidences of upper GI complaints, such as dyspepsia were reported.19-21 However, prospective studies involving untreated osteoporosis patients to compare therapeutic efficacy and side effects of different bisphosphonates are limited. Intravenous bisphosphonates may be followed by an acute-phase reaction within one to 3 days of infusion, characterized by low-grade temperature, and muscle and joint pain. The current study was carried out to evaluate the efficacy of orally-administered alendronate compared with intravenously-administered zoledronate. Our starting hypothesis was that zoledronate would be as effective as alendronate but with no, or fewer, GI-associated adverse events. Changes in lumbar spine and hip BMD in patients with osteoporosis receiving either a single intravenous (i.v.) dose of zoledronate at 5 mg/year, or oral alendronate at 70 mg/week in a clinical setting were compared.