Screening for urine abnormalities among preschool children in western Saudi Arabia

Objectives:

To estimate the frequency of urinary problems among preschool children.

Methods:

In this cross-sectional study, 1000 preschool asymptomatic children attending the outpatient clinics of the Children’s Hospital, Taif, Kingdom of Saudi Arabia between August 2013 and December 2013 were subjected to dipstick urine analysis. Microscopic examination was performed for the abnormal dipstick samples, and children with hematuria were investigated for kidney function.

Results:

Dipstick urine analysis revealed abnormal findings in 25.1% of the screened children. The most common dipstick abnormalities were positive nitrite test in 18.1%, hematuria in 16.9%, and positive leukocyte esterase test in 14.3% of the cases. The most common abnormality in microscopic urine examination was crystals in 13% of the cases. Pyuria were evident in 5% of cases and hematuria in 2.5%. The most common bacteria in positive urine culture samples was Escherichia coli in 62.6%.

Conclusion:

In view of these important findings, dipstick screening should be implemented in preschool children.Chronic kidney disease (CKD) is a global public health problem, its incidence is steadily increasing among children.1 The Kingdom of Saudi Arabia (KSA) is a large country (26.9 million) populated with a high percentage of children; children aged 0-14 years represent 28.2% of the population.2 The Kingdom of Saudi Arabia is similar to other developing countries in that there is no current national epidemiologic data on pediatric chronic renal failure (CRF) and its risks.3 Detection and management of renal problems in children are of major importance for CKD prevention; this in turn will decrease the burden of CKD in the pediatric population.4 Urinalysis is recognized as the simplest and least expensive method for screening healthy children and dipstick method is the most commonly implemented procedure.5 Moreover, dipstick has proven effective in prediction of rapidly declining kidney function.6 It must be recognized that not all abnormal results are clinically significant, and that false positive and false negative results can exist.7 Moreover, there is uncertainty as to whether early detection of renal disorders in children will lead to prevention of development of end-stage renal disease (ESRD). However, there is a clear consensus among Japanese, Taiwanese, and Korean investigators that the screening programs currently in place in these counties have led to early detection and effective intervention.8 Proteinuria and hematuria are among the early manifestations of renal disease.9 The presence of a dipstick test 1+ or ≥2+ for proteinuria was strongly associated with renal risk.10 Hematuria can be caused by several conditions, including infections, stone disease of the urinary tract, glomerular, and tubular disorders.11 Nitrite in urine has also been used to diagnose urinary tract infection; a common condition in childhood with serious complications.12 The treatment of persistent proteinuria should be directed toward the underlying cause. Steroid therapy may be used. Other therapies may be required in patients with renal dysfunction (namely, cyclophosphamide, chlorambucil, cyclosporine). Additionally, angiotensin-converting enzyme inhibitor and/or angiotensin-II receptor blocker can be used to the slow progression of renal disease and decreasing proteinuria. Referral to a pediatric nephrologist may be needed for further management.13 The aim of the current study was to screen for hematuria and other urine abnormalities among children in Taif city, as early detection could aid in preventing the progression of renal diseases.     

Diagnostic efficacy of random albumin creatinine ratio for detection of micro and macro-albuminuria in type 2 diabetes mellitus

Objectives:

To compare a less cumbersome random albumin creatinine ratio (RACR) with 24-hour urinary albumin excretion (UAE) for detection of renal damage in patients with type 2 diabetes mellitus (T2DM).

Methods:

This retrospective study performed between March 2013 and June 2014 at the Department of Pathology, King Khalid University Hospital, Riyadh, Kingdom of Saudi Arabia included 122 patients (mean age 54±15, 104 females and 18 males) with T2DM. Urine albumin levels of <30 mg/g was considered normal, from 30-300 mg/g considered as micro-albuminuria, and over 300 mg/g considered as macro-albuminuria.

Results:

Concordance between the 2 assays was observed in 114 (93.4%) samples. The sensitivity of RACR assay was 100%, specificity was 91.3% with a positive predictive value (PPV) of 95%, and a negative predictive value (NPV) of 100% in micro-albuminuria range. For macro-albuminuria, RACR had a sensitivity of 100%, specificity of 94.1% with PPV of 94% and NPV of 100%. Receiver operating characteristic (ROC) curves analysis cut-off values of 40 mg/g-300 mg/g for micro- and >300 mg/g for macro-albuminuria revealed 100% sensitivity, 97.5% specificity, 95% PPV, and 100% NPV for micro-albuminuria, and 100% sensitivity, 94% specificity, 76% PPV, and 100% NPP for macro-albuminuria. The area under the curve for micro-albuminuria was 100% and 98.2% for macro-albuminuria.

Conclusion:

Performance of RACR was comparable to 24 hour UAE assay particularly in excluding renal damage in T2DM.Diabetes related chronic kidney disease (CKD) is among the serious micro-vascular complications of type 2 diabetes mellitus (T2DM), and is a leading cause of end-stage renal disease.1 Between 30-40% of patients with diabetes develop CKD that manifests as albuminuria, or decreased glomerular filtration rate.2-4 The prevalence of diabetes-related CKD is increasing alongside the prevalence of diabetes all over the world.5 Micro-albuminuria is a term used for a relatively small amount of albumin excretion in urine in the early stages of CKD in diabetics. This may progress to overt proteinuria in 20-40% of diabetics in 10 years culminating in end-stage renal disease in approximately 20% of patients.6,7 The presence of diabetes, irrespective of new-onset, or previously diagnosed diabetes poses a 2.5 fold increased risk of albuminuria.8 Screening for micro-albuminuria early in the disease particularly in T2DM is, therefore, critical in salvaging kidneys as it is a potentially reversible form of kidney injury.9 The gold standard for assessment of albuminuria is the estimation of albumin concentration in a urine sample collected over 24-hours as the outcome will not be affected by the variations in protein excretion during the day.10,11 This procedure, however, has several limitations, such as sample collection errors on part of the patient, poor compliance, extended duration of sample collection, and is not cost effective.12-14 Since the excretion of creatinine and protein remains constant if the glomerular filtration is stable15 measurement of protein to creatinine in a spot, or random urine sample would not be affected by the variations in protein and albumin excretion in urine samples.16 Measurement of random urine albumin creatinine ratio (RACR) has been evaluated in a number of studies demonstrating a close relationship with 24-hour protein excretion.17,18 The existing data, however, falls short of certainty with which RACR might be used to rule in, or rule out proteinuria. This study was performed to assess the performance of RACR against the gold standard estimation of 24-hour urinary albumin excretion (UAE) for detection of micro-albuminuria in Saudi patients with T2DM.     

Can pre-implantation biopsies predict renal allograft function in pediatric renal transplant recipients?

Objectives:

To determine the utility of pre-implantation renal biopsy (PIB) to predict renal allograft outcomes.

Methods:

This is a retrospective review of all patients that underwent PIB from January 2003 to December 2011 at the Great Ormond Street Hospital for Children in London, United Kingdom. Thirty-two male patients (56%) aged 1.5-16 years (median: 10.2) at the time of transplantation were included in the study and followed-up for 33 (6-78) months. The results were compared with 33 controls.

Results:

The PIB showed normal histopathological findings in 13 patients (41%), mild chronic vascular changes in 8 (25%), focal tubular atrophy in one, moderate to severe chronic vascular change in 3, mild to moderate acute tubular damage in 6, and tissue was inadequate in one subject. Delayed graft function (DGF) was observed in 3 patients; 2 with vascular changes in PIB, and one with normal histopathological findings. Two subjects with PIB changes lost their grafts. The estimated glomerular filtration rate at 3-, and 6-months post-transplantation was lower in children with abnormal PIB changes compared with those with normal PIB. There was one case of DGF in the control group, and 4 children lost their grafts including the one with DGF.

Conclusion:

Pre-implantation renal biopsy can provide important baseline information of the graft with implications on subsequent medical treatment for pediatric renal transplant recipients.Pre-implantation or implantation biopsies (PIB) have been used in adult renal transplantation for the last 2 decades.1 The PIB of the donor kidney was initially suggested by Gaber et al2 in 1992 as they found that pathological changes correlated with subsequent renal allograft rejection and loss. They reported that the presence of polymorphonuclear (PMN) leucocytes marginating in the peritubular capillaries is related to the subsequent occurrence of cellular rejection, and an elevated mean glomerular PMN leucocyte count in conjunction with an elevated peritubular PMN leucocyte count was always associated with hyperacute rejection.2 Many adult renal transplant recipients have PIB performed on a routine basis, or as part of clinical studies as it is believed that major histological injuries are the leading causes of long-term chronic allograft dysfunction.3 This includes glomerular injury, vascular injury, and tubulointerstitial injury, such as interstitial fibrosis (IF), and tubular atrophy (TA).1 Pre-implantation or implantation biopsies is particularly useful when using marginal kidneys from deceased donors (DD), such as donation after cardiac death (DCD) as it is more likely to show donor pathology, such as glomerulosclerosis (GS), IF, hypertensive vascular changes and TA, which predict a subsequent worse renal allograft survival.1,4-6 It was reported that baseline biopsies with severe vascular disease correlated with delayed graft function (DGF), acute rejection episodes, and renal allograft dysfunction with increased serum creatinine levels at 18 months post-transplantation.6 Eapen et al7 reported that the percentage of acute rejections episode with normal PIB was 48% compared with 75% of patients with abnormal PIB. Furthermore, the quality of the donor organ at implantation was strongly predictive of subsequent renal histology in allografts functioning at 3 months.8 The GS percentage is directly correlated to renal allograft survival, DGF, and primary non-function.9 There is evidence that early transplant damage occurs in the tubulointerstitial compartment from pre-existing donor kidney injury and subsequent chronic damage, and renal allograft failure reflect accumulated previous injury.10 There is a lack of studies in the pediatric populations regarding the use of PIB and its correlation with renal allograft function. In this study, we investigated the utility of PIB to predict early- and long-term renal allograft outcome in pediatric renal transplant recipients (PRTR).     

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.     

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.     

Cardiac lymphangioma presenting as intrapericardial cystic mass

Cystic lymphangioma usually confined to head and neck is a well-recognized tumor that occurs during childhood. However, a cardiac lymphangioma is exceptionally uncommon and a particularly rare form of disease. We report a case of cystic lymphangioma arising from the right ventricular wall, and presenting as pericardial mass in a young female, who presented with a history of exercise intolerance in the form of breathlessness on exertion and palpitations. The management of such a case was a difficult task; however, she underwent near total resection of the mass, and is doing well for the last 2 years.Cardiac tumors are rare but potentially curable form of heart disease with incidence ranging from 0.0017-0.33% at autopsy. A high index of clinical suspicion is necessary for diagnosis as these tumors have protean manifestations that mimic a variety of other cardiac and noncardiac diseases.1,2 Most (>80%) of these tumors are benign, and myxoma is by far the most common. Myxoma constitutes approximately 50% of all benign cardiac tumors in adults, but only a small percentage of such tumors in children. Rhabdomyoma is the most common benign tumor in children, and accounts for 40-60% of cases. Other benign cardiac tumors include fibromas, lipomas, hemangiomas, papillary fibroelastomas, cystic tumors of the atrioventricular node, and paragangliomas. The remaining 20% of primary cardiac tumors are malignant, and are usually described as sarcomas.3 Cystic lymphangioma, usually confined to head and neck, is a well-recognized benign tumor that occurs during childhood. However, a cardiac lymphangioma is exceptionally uncommon and a particularly rare form of cardiac disease, and is considered to be a malformation that arises from sequestration of lymphatic tissue that fails to communicate normally with the rest of the lymphatic system.1,4,5 Cardiac lyphangiomas most frequently occur in the pericardial space, sometimes compressing adjacent structures; a chylous pericardial effusion may be present.6,7 The presentation in most cases is usually but not necessarily dramatic or acute, and the type of symptoms depends on the site and degree of involvement, ranging from syncope or palpitations to arrhythmia, or congestive heart failure.4,5 All imaging studies can provide information regarding the anatomic details of the mass, however to obtain final diagnosis and treatment, patient’s need surgical exploration and resection of the mass as was seen in our case.1,4,5 The objective in presenting this particular case is to highlight its atypical clinical picture and diagnostic uncertainty until surgical exploration.     

Urinary tract infection in children younger than 5 years: Etiology and associated urological anomalies

Objectives:

To investigate the most common underlying organisms, and associated urological anomalies in children presenting with urinary tract infection (UTI).

Methods:

Retrospectively, all children with confirmed UTI between October 2013 and February 2014 were evaluated at King Abdulaziz University Hospital, Riyadh, Kingdom of Saudi Arabia. The electronic files of 279 children presenting with UTI, aged less than 5 years were reviewed.

Results:

A total of 153 patients (85 males) with a mean (SD) age of 15 (19.86) months were included in the study. Recurrent UTI was present in 45.1%. Urine collection in children less than 2 years of age was through trans-urethral catheterization in 69.4%, while midstream urine was the main method in those above 2 years (78.6%). Escherichia coli (E. coli) was the causative organism in 41.2% of first UTI. The second most common organism was Klebsiella Pneumoniae, seen in 19.6%. Urological anomalies were found in 28.1% of the overall study population. Ninety percent of those with single UTI did not have anomalies. However, urological anomalies were reported in 50.7% of those with recurrent episodes of UTI (p<0.005). Non-E. coli cases were associated with a higher percentage of abnormal renal ultrasonography results (p=0.006).

Conclusion:

Escherichia coli was the most common causative organism for UTI, and a single episode of UTI signified normal urological anatomy.Urinary tract infection (UTI) is common in children. Early diagnosis and management is essential to minimize the acute morbidity and prevent the long-term complications associated with UTI, which include hypertension and renal scarring. However, considerable controversy prevails in the diagnosis and management of UTI in children.1 Major changes have also been presented in recent treatment guidelines.2,3 Blood investigations such as leukocyte count with urine analysis and inflammatory markers such as C-reactive protein (CRP), and erythrocyte sedimentation rate (ESR), might indicate the presence of an infection, but confirmation is only by urine culture. Midstream urine is the standard method in older children, but in young children selecting the best-suited method of urine collection is crucial to avoid false positive results. Using urine bags for collecting specimens for culture is discouraged as it increases the possibility of false positive results.4 Urinary tract infection is associated with renal anomalies in children,1 and investigation of affected children is recommended to diagnose renal anomalies. An ultrasound study is recommended by both the American Academy of Pediatrics,2 as well as the National institute of Clinical Excellence (NICE)3 as initial screening. Voiding cystourethrogram (VCUG) is used to detect vesicoureteral reflux, and DMSA (dimercaptosuccinic acid) scan to detect renal scars.1-3 The DMSA scan is recommended before VCUG by NICE in children aged 6 months to 3 years.3 The DMSA scan could replace VCUG as the first line procedure, and this approach is recommended by many investigators.5 In Saudi Arabia, due to a high rate of consanguinity,6 the risk of renal anomalies looms large; it is believed that up to 70% of renal anomalies in children can be attributed to an underlying genetics cause.7 In this study, we aimed to detect abnormal renal US findings in children aged <5 years with a UTI, and compare the etiology of infection and abnormal US finding in cases with first episode of infection with those with recurrence of infection.     

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.     

Histopathological and immune alterations in autopsied kidneys

Objectives:

To collect data on all detectable histologic and immune alterations from the kidneys of 55 autopsy cases.

Methods:

This prospective study was carried out at the Department of Pathology, Medical Faculty, Trakya University, Edirne, Turkey. Fifty-five cases were subjected to the study among 248 autopsies that were performed in 2011 and 2012. All kidney samples were evaluated under a light microscope and fresh tissue samples were used for immunofluorescence microscopy. Immunohistochemically kappa (κ) and lambda (λ) antibodies were applied to the tissue sections. The glomerular, tubulo-interstitial, and vascular alterations, as well as immune depositions were noted.

Results:

The microscopic morphology was close to normal histology in only 23 cases, and 23 cases had glomerular alterations. Nineteen cases had at least one immune deposition. There was immunoglobulin A deposition in 13 cases, and 9 cases showed positivity for both κ and λ immunohistochemically, and there was no clonal positivity.

Conclusion:

The most striking outcome of our study is the high rate of immune depositions. There was also a significant number of glomerular and non-glomerular renal alterations.End stage kidney disease (ESKD) is one of the leading health problems worldwide with high morbidity, and mortality rates.1,2 Biopsy proven data shows that glomerulonephritis (GN) is the most important cause of chronic renal insufficiency, in which primary GN comprises the biggest proportion, especially in Western and Eastern Europe.3,4 Vascular diseases (VDs) and tubulointerstitial diseases (TIDs) seem to be less frequent diseases leading to chronic renal insufficiency. However, biopsy policies and biopsy indications are changing from country to country, and in daily practice kidneys prone to VDs and TIDs are rarely biopsied in most regions. Regarding the daily clinical practice, although they are not proven by biopsies, VDs, and TIDs seem to be the leading cause of chronic renal insufficiency worldwide, where the former is a more important reason when compared with the latter. Among acute lesions developing renal insufficiency, tubular injury takes place after crescentic GN and necrotizing vasculitis.4,5 Incidence and prevalence studies of chronic renal diseases are mostly based on native renal biopsies, which usually depends on single center studies along with a retrospective review of the diagnostic criteria obtained from the files of patient registries.6-12 There are rarely regional multicenter or national studies, in which the diagnostic data are obtained from the national registry system for renal biopsies.1-5,13,14 These types of studies are of importance as they investigate the incidence of the categorized renal diseases to determine the leading causes of ESKD. However, it should be kept in mind that they are providing data only from a symptomatic population. Population based studies are needed to obtain the real incidence of renal lesions in an asymptomatic population. Although there are some retrospective studies on kidneys of patients that underwent nephrectomy due to kidney masses,15 it is not assumable that the data of those studies can reflect the real incidence of alterations in otherwise normal kidneys of the population. Thus, autopsy studies play an important role in achieving the closest information towards this target. There are a few autopsy studies related to renal diseases in the literature. Two of those studies16,17 aimed to investigate GN due to hepatitis C virus infection retrospectively in autopsy cases with prior known hepatitis C virus infection, thus, they did not provide any data regarding other possible causes of kidney diseases related to primary or secondary GN, VDs, or TIDs. The Hisayama study18 was a large retrospective autopsy study with 839 subjects, and the risk factors for glomerular sclerosis and vascular changes were sought without assistance of immunofluorescence or immunohistochemistry and lacked detailed data for possible reasons of glomerular sclerosis, except for the reasons of glomerular sclerosis based on vascular disorders of the kidneys. In a prospective autopsy kidney study,19 which was conducted on a West African urban community, the authors investigated the glomerular numbers and volumes, as well as renal pathology in 81 subjects. In this study,19 the histopathological changes were assessed with histochemical methods without guidance of immunofluorescence microscopy. In Turkey, there is very limited information regarding the epidemiology of kidney diseases, and it is mainly based on a few single center studies, concerned with retrospective evaluation of the data obtained from previous renal biopsies.20-22 Very recently a national registry system was created in Turkey for medical kidney biopsies, but we still need time to receive the first reliable data from this system. In the present study, we aimed to collect data obtained from the kidneys of 55 autopsy cases, regarding all detectable histologic and immune alterations. Likewise, we aimed to provide a regional data regarding kidney lesions in an asymptomatic population.     

Gender equality in the work of local research ethics committees in Europe: a study of practice in five countries

Background

Funding organisations and research ethics committees (RECs) should play a part in strengthening attention to gender equality in clinical research. In the research policy of European Union (EU), funding measures have been taken to realise this, but such measures are lacking in the EU policy regarding RECs.

Objective

To explore how RECs in Austria, Germany, Ireland, The Netherlands and Sweden deal with gender equality issues by asking two questions: (1) Do existing procedures promote representation of women and gender expertise in the committee? (2) How are sex and gender issues dealt with in protocol evaluation?

Methods

Two RECs were selected from each country. Data were obtained through interviews with key informants and content analysis of relevant documents (regulations, guidelines and review tools in use in 2003).

Results

All countries have rules (mostly informal) to ensure the presence of women on RECs; gender expertise is not required. Drug study protocols are carefully evaluated, sometimes on a formal basis, as regards the inclusion of women of childbearing age. The reason for excluding either one of the sexes or including specific groups of women or making a gender‐specific risk–benefit analysis are investigated by some RECs. Such measures are, however, neither defined in the regulations nor integrated in review tools.

Conclusions

The RECs investigated in five European member states are found to pay limited attention to gender equality in their working methods and, in particular in protocol evaluation. Policy and regulations of EU are needed to strengthen attention to gender equality in the work of RECs.Clinical research has a crucial role in the provision of high‐quality care. It provides healthcare professionals with information on optimal strategies for the prevention, diagnosis and treatment of health problems. Public funding organisations and local research ethics committees (RECs) have a key role in the assessment of quality in clinical studies. Although the funding organisations evaluate the proposals according to scientific standards and relevance, RECs assess their ethical soundness, guided by the principles of respect for people and their autonomy, doing no harm, doing good and justice.¹It was assumed for many years that, apart from the reproductive system, there were few differences between men and women that affected health. Clinical studies on conditions that affect both men and women were mostly conducted with male research participants and were not designed to identify differences between men and women or relevant subgroups. It has, however, been recognised since the 1990s that marked differences exist in patterns of health and in conditions that affect both men and women: some conditions are more prevalent or more serious in one sex than the other, have distinct risk factors for men and for women or require different interventions.^2,3 These differences may stem from specific biological characteristics of women and men (reproductive, genetic, hormonal and metabolic features; sex), or from differences in socially constructed variations in the daily lives of men and women (gender), which interact in complex ways.^3,4,5,6,7,8 In addition, it has been suggested that the earlier research bias with relation to men without considering possible differences between the sexes has created gaps in our knowledge, both of disease management in women^2,3,9,10 and of how gender affects health.^6,10,11,12 To fill these gaps, researchers should consider both women and men and design their studies with sensitivity to sex and gender factors.^{3,4,5,8,9,13,14}In response to a concern that such lack of information may hamper optimal healthcare to both men and women, public funding organisations in several countries have adapted their rules for research applications. For example, supported by a mandate from the US Congress, the US National Institutes of Health required since 1993 that men and women should both be adequately represented in clinical studies and that research designs should permit valid and meaningful analysis of differences between the sexes.¹⁵ More recently, the European Union (EU) has made a clear commitment to promote gender equality in research funded by the EU by aiming at balanced participation of male and female scientists in projects (40% women) and attention to gender in the research content.¹⁶ With respect to the attention to gender, study proposals must consider the needs and interests of women as much as those of men. In the sixth Framework Programme, which started in 2002, applicants for projects in the life sciences were asked to describe and justify the composition of the study population according to sex and to integrate attention to sex and gender issues, whenever relevant, in the objectives and methods of their research projects.¹⁶The revised National Institutes of Health policy presented real challenges to the institutional reviews boards, which are responsible for the ethical review in the US, on how to carry out the ethical assessment of study protocols. Until 1993, the work of the institutional review boards was guided by the ethics of protectionism, often resulting in the exclusion of women, especially pregnant women or women of childbearing age, from research to protect them and their unborn children from potential harm.¹⁴ The new regulations also instructed the boards to examine issues of justice and equitable selection of participants.¹⁷ A new balance had to be found, with less emphasis on protection and more on inclusion: to be fair in the selection of research participants, a study should include all relevant groups, including women, unless there are sound scientific reasons for not doing so. Furthermore, the study design should be attuned to the specific needs of the groups included, to avoid an unfair distribution of benefits and burdens.^8,17,18,19A similar shift in focus is also visible in other national^20,21,22,23 and international^24,25,26,27 guidelines on research ethics. Besides ensuring that study participants are protected from harm, RECs should evaluate whether there is equitable representation of men and women^24,25,26,27 and whether burdens and benefits associated with participation are equitably distributed across the sexes.^24,25,26 Another issue is whether drug studies take possible sex differences in drug metabolism into consideration.²⁷ In addition, some guidelines mention that RECs must include both men and women as evaluators of research proposals.^24,25,26 Surprisingly enough, however, the recently adopted directive of the EU on clinical research, which is intended to harmonise the working methods of RECs in the member states, does not contain any reference to sex or gender. Directive 2001/20/EC of the European Parliament and of the Council of 4 April 2001 on the approximation of the laws, regulations and administrative provisions of the member states relates to the implementation of good clinical practice in the conduct of clinical trials on medicinal products for human use.To provide a firmer basis for decision making, there is a need to know how much attention is paid to gender equality in the existing procedures of RECs in member states of the EU. To this end, we conducted an exploratory study in Austria, Germany, Ireland, The Netherlands and Sweden in which the following questions were asked: Do existing formal or informal arrangements require a REC to include women or an expert on health‐related sex and gender issues on the committee? Do existing formal and/or informal arrangements for the evaluation of research protocols pay attention to sex and gender factors in the design and conduct of a study?     

Failure rate of inferior alveolar nerve block among dental students and interns

Objectives:

To report the failure rate of inferior alveolar nerve block (IANB) among dental students and interns, causes of failure, investigate awareness of different IANB techniques, and to report IANB-associated complications.

Methods:

A 3-page questionnaire containing 13 questions was distributed to a random sample of 350 third to fifth years students and interns at the College of Dentistry, King Saud University, Riyadh, Saudi Arabia on January 2011. It included demographic questions (age, gender, and academic level) and questions on IANB failure frequency and reasons, actions taken to overcome the failure, and awareness of different anesthetic techniques, supplementary techniques, and complications.

Results:

Of the 250 distributed questionnaires, 238 were returned (68% response rate). Most (85.7%) of surveyed sample had experienced IANB failure once or twice. The participants attributed the failures most commonly (66.45%) to anatomical variations. The most common alternative technique used was intraligamentary injection (57.1%), although 42.8% of the sample never attempted any alternatives. Large portion of the samples stated that they either lacked both knowledge of and training for other techniques (44.9%), or that they had knowledge of them but not enough training to perform them (45.8%).

Conclusion:

To decrease IANB failure rates for dental students and interns, knowledge of landmarks, anatomical variation and their training in alternatives to IANB, such as the Gow-Gates and Akinosi techniques, both theoretically and clinically in the dental curriculum should be enhanced.Profound local anesthesia is administered in preparation for many dental procedures.1 The practice was pioneered by Halsted and Hall, who, in 1884, introduced the technique of injecting a cocaine solution into the region of the mandibular foramen.2 Today, the inferior alveolar nerve block (IANB) is commonly used to induce local anesthesia for various applications throughout modern dentistry.3 However, IANB failure rates can be substantial, reaching 15-20%,4 and often cannot be overcome with a repeat IANB injection.5 Inferior alveolar nerve block failure has been attributed to technical errors, pathological processes (namely, trismus), infection, inflammation, previous surgery and psychological causes, such as fear, anxiety and apprehension.3 Poor technique has been reported to be the most common reason for failure of conventional IANB.4,6 Specifically, poor technique may be related to inadequate mouth opening, incorrect needle placement (too anterior or posterior), or failure to give enough time for the anesthesia to work.6 Malamed5 has recommended waiting 3-5 minutes after the injection before starting the procedure. The standard IANB procedure (Figure 1A) is a direct technique wherein the practitioner places his or her thumb intra-orally at the deepest concavity of the anterior ascending ramus. The point of injection is located midway between the midpoint of the thumb nail and the pterygomandibular raphe. The needle is advanced 15-25 mm parallel to the occlusal plane of the contralateral premolars until it reaches the proper bony end point injection site.1 In a 2014 review, Khalil7 discussed alternative techniques for overcoming conventional IANB failure. The Gow-Gates technique (also known as the high mandibular block)8 and the Vazirani-Akinosi closed-mouth technique,9 for example, have been available for more than 40 years. Additionally, some have suggested that anesthesia quality can be improved by injecting anesthetic solution into intraligamentary and intra-osseous areas.10 The Gow-Gates technique8 (Figure 1B), which was introduced in 1973 is credited with several advantages, such as use of only a single injection, minimal positive aspiration rate, low risk of complications, higher success with anatomical variations, minimal pain, and stable landmarks.11 Notably, in a study of 4,275 cases, Malamed12 observed a decreased incidence of trismus with the Gow-Gates technique, relative to conventional IANB, upon evaluation of 4,275 cases.12 The Akinosi9 closed-mouth technique (Figure 1C), which was introduced in 196013 has also been advocated for overcoming IANB failure. It is simpler than the Gow-Gates technique and does not depend on bony contact. Both the Gow-Gates technique and the Vazirani-Akinosi technique involve anesthetizing the inferior alveolar nerve, lingual nerve, and long buccal nerve with a single injection.1 In a 2010 study, Aggarwal et al14 observed a significantly better success rate for mandibular molar anesthesia with the Gow-Gates technique (52%) than with conventional IANB (36%), with an intermediate success rate (41%) for the Vazirani-Akinosi technique, and a relatively poor success rate (27%) for infiltrations. Remarkably, Jung et al10 found that buccal-plus-lingual infiltrations could provide satisfactory anesthesia in 32-67% of patients if lidocaine was used, and in 57-92% of patients if articaine was used, even without the use of standard IANB. Although the mentioned alternative techniques are well-established, Johnson et al15 found that nearly half (47.5%) of Harvard dental students alumni (classes 2000-2006) not only had never used an alternative technique, but further stated that they felt no need for an alternatives. The aims of this study were 1) to assess IANB failure rate among dental students and interns, and how it was overcome, 2) to report the causes of failure, 3) to investigate the awareness of alternative techniques, and 4) to assess IANB-related complications.Open in a separate windowFigure 1Delivery of anesthesia by: A) standard inferior alveolar nerve block; B) Gow-Gates alternative technique; and C) Vazirani-Akinosi alternative technique.     

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     

Glutaric aciduria type 1 as a cause of dystonic cerebral palsy

Glutaric aciduria type 1 (GA1) is an inherited inborn error of metabolism caused by a deficiency of the enzyme glutaryl Co-A dehydrogenase (GCDH). Here, we report a 14-month-old Saudi boy with GA1 who presented with severe dystonia and was mis-diagnosed as cerebral palsy (CP). He presented to our institute with encephalopathy following an episode of gastroenteritis. His physical examination showed dystonia and spastic quadriplegia. His investigations revealed elevated both urinary 3-hydroxy glutaric acid, and serum glutarylcarnitine. The DNA analysis confirmed homozygosity for a mutation in the GCDH-coding gene (c.482G>A;p.R161Q). This case alerts pediatricians to consider GA1 as a differential diagnosis of children presenting with dystonic CP.Glutaric aciduria type 1 (GA1) (OMIM #231670) is an inherited autosomal recessive metabolic disorder caused by mutation in the glutaryl Co-A dehydrogenase (GCDH) gene.1 This gene maps to chromosome 19p13.2. If mutated, it results in deficiency of the enzyme GCDH.1 This mitochondrial enzyme is involved in the metabolism of lysine, hydroxylysine, and tryptophan.2 Its deficiency lead to accumulation of glutaric and 3-hydroxyglutaric acids, which are toxic to the brain and cause striatal injury. The prevalence of GA1 is estimated to be one in 100,000 newborns.3 Affected individuals in infancy, may initially present with macrocephaly, but otherwise, they are neurologically healthy. Encephalopathy is usually triggered by intercurrent infection, such as acute gastroenteritis, which affects most untreated patients.4 It may progress to severe dystonia, choreoathetosis, and spastic quadriplegia if left untreated.4 When presented clinically, GA1 is usually diagnosed by measuring serum glutarylcarnitine, urinary excretion of glutaric, and 3-hydroxyglutaric acid.2 To prevent permanent and irreversible neurological damage, screening for GA1 has been included in expanded neonatal screening programs in many countries.3,4 A positive glutarylcarnitine blood spot-screening test requires assessment of urine organic acids.2 The diagnosis of GA1 is confirmed by measuring GCDH enzyme activity, or performing mutation analysis.4 Different mutations have been reported in the GCDH gene.5,6 The aim of management in GA1 is to prevent neurological complications, including movement disorders and seizures. Treatment consists of low lysine diet with L-carnitine supplementation. Favorable outcome was reported in patients who were diagnosed and started treatment early.3 We report a Saudi child with GA1 who presented with dystonia and misdiagnosed as cerebral palsy (CP) to alert pediatricians to consider GA1 as a differential diagnosis in patients with dystonic cerebral palsy, as early intervention will prevent permanent neurological damage.     

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.     

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).     

A novel mutation in ornithine transcarbamylase gene causing mild intermittent hyperammonemia

We report a 3-year-old Saudi boy with recurrent episodes of vomiting, poor feeding, and altered mental status accompanied by an intermittent mild hyperammonemia, and a large elevation of urinary orotic acid. Sanger sequencing of the ornithine transcarbamylase (OTC) gene revealed a novel hemizygous deletion at the fourth nucleotide of intron 4 (c.386+4delT) in the proband and his asymptomatic mother. This novel mutation in the OTC gene is responsible for the late-onset phenotype of OTC deficiency.Hyperammonemia is a life-threatening condition caused by inherited and acquired diseases. Urea cycle disorders (UCD) are the leading inborn errors that present with hyperammonemia.1 All the 6 urea cycle enzyme defects are inherited as autosomal recessive except ornithine transcarbamylase (OTC) deficiency (OTCD; MIM#311250), which is an X-linked disease.2 Ornithine transcarbamylase is a mitochondrial enzyme that catalyzes the second step of the urea cycle leading to the synthesis of citrulline from ornithine and carbamoyl phosphate.1 The prevalence of OTC deficiency is estimated to range from 1 in 40,000 to 1 in 80,000.3,4 The phenotype of OTC deficiency is extremely heterogeneous. Patients with OTC deficiency usually present with poor feeding, vomiting, and respiratory alkalosis, and may progress to seizures, encephalopathy, and death.1 Late-onset disease presents beyond the neonatal period with life-threatening hyperammonemia and occasionally with intermittent episodes of metabolic decompensation.5 These patients with late-onset disease usually have more residual enzyme activity compared to classic OTC phenotype. Aside from the clinical phenotype, the diagnosis of OTC deficiency is based on the presence of hyperammonemia, high glutamine, and low arginine in serum amino acid and demonstration of orotic aciduria.2 Previously, enzyme study using liver biopsy tissues was the gold standard for the diagnosis of this condition.1 Currently, the diagnosis is confirmed by detection of the pathogenic mutation(s) in the OTC gene. The human OTC gene was mapped to the short arm of chromosome Xp21.1 and encodes a 354 amino acids protein.2 There exists mutational heterogeneity in the OTC gene. More than 341 mutations have been identified in the OTC gene that are distributed throughout the gene and most of which are private mutations.5 A large number of reported variants are missense mutations (68%), followed by nonsense, insertions, and deletions in the coding region (18%). The remaining variants include splice site variants affecting splicing of OTC mRNA.5,6 In this study, we report a novel mutation in the OTC gene in a Saudi boy who presented with mild intermittent hyperammonemia.