The Gln27Glu Polymorphism in β2-Adrenergic receptor gene is linked to hypertriglyceridemia,hyperinsulinemia and hyperleptinemia in Saudis

Background  

β2-adrenoceptor (β2AR) gene polymorphism glutamine 27 glutamic acid (Gln27Glu) and Arg16Gly were reported to have an association with obesity and obesity related disorders in some population. We evaluated Gln27Glu polymorphism in the β2AR gene in obese Saudi populations to investigate the association of β2AR gene with obesity and other related metabolic parameters.     

Glucocorticoids do not protect against the lethal effects of experimental heatstroke in baboons

The mortality and neurological morbidity in heatstroke have been attributed to the host's inflammatory responses to heat stress, suggesting that anti-inflammatory therapy may improve outcome. We tested the hypothesis that a high dose of dexamethasone protects baboons against the lethal effects of heatstroke. Ten anesthetized baboons (Papio hamadryas) were assigned randomly to dexamethasone (n = 5) or control group (n = 5). Dexamethasone (2 mg/kg i.v.) was administered in four divided doses every 6 h starting immediately before heat stress and continuing during cooling. All animals were heat-stressed in a prewarmed neonatal incubator at 44 degrees C to 47 degrees C until systolic blood pressure fell less than 90 mmHg and then cooled passively at the ambient temperature. Mortality and neurological morbidity were noted, and biochemical markers of tissue injury/organ dysfunction were determined. Circulating interleukin (IL) 6 and complement components (C3 and C4) were measured sequentially. All heat-stressed animals had systemic inflammation indicated by increased plasma IL-6 and decreased C3 and C4 levels. Dexamethasone attenuated the complement system activation and maintained a higher plasma concentration of IL-6, with a significant augmentation of arterial blood pressure. Dexamethasone did not prevent the occurrence of severe heatstroke but unexpectedly aggravated significantly the tissue injury and multiorgan system dysfunction. Two animals (40%) in the control group and one in the steroid group survived (P > 0.05). Dexamethasone failed to protect the baboons from the lethal effects of heatstroke. These results do not support clinical testing of corticosteroids as beneficial in preventive or therapeutic strategies for the treatment of heatstroke in humans.     

Immediate and long-term results of percutaneous mitral balloon valvotomy in asymptomatic or minimally symptomatic patients with severe mitral stenosis.

The purpose of this study was to evaluate the safety and value of percutaneous mitral balloon valvotomy (PMBV) in asymptomatic or minimally symptomatic patients with severe mitral stenosis (MS). There are very limited data supporting the concept of PMBV in asymptomatic or minimally symptomatic patients with severe MS. We analyzed the results of 539 consecutive patients with severe MS who underwent PMBV at our hospital. Patients were divided according to their symptoms at the time of PMBV into group A (55 patients), who had few or no symptom (NYHA class 1 or 2), and group B (484 patients), who had severe symptom (NYHA class 3 or 4). Patients had clinical and echocardiographic follow-up for 0.5-15 years. There was no significant difference in baseline characteristics between the two groups. The immediate mitral valve area (MVA) was equal in both groups. The follow-up MVA was larger in group A (1.9 +/- 0.38 vs. 1.7 +/- 0.4 cm(2); P = 0.002), and restenosis occurred in 11% in group A vs. 23% in group B (P = 0.023). Actuarial freedoms from restenosis at 5, 10, and 13 years were significantly higher for group A than for group B (97% +/- 2%, 77% +/- 9%, 77% +/- 9% vs. 85% +/- 1%, 62% +/- 3%, 39% +/- 5%; P = 0.0018). Atrial fibrillation at follow-up was encountered in 11% in group A vs. 20% in group B (P = 0.042). There was a significant reduction of the left atrial size in both groups. Event-free survivals at 5, 10, and 13 years were higher for group A than for group B (97% +/- 2%, 80% +/- 9%, 80% +/- 9% vs. 86% +/- 1%, 65% +/- 3%, 42% +/- 3%; P = 0.0018). This study demonstrated excellent immediate results of PMBV in asymptomatic or minimally symptomatic patients with severe MS and long-term results are better compared to the reported natural history of such patients. We recommend mitral balloon valvotomy (MBV) for patients with severe MS with few or no symptoms, provided the valve morphology is suitable for MBV.     

Nonpain Symptoms of New and Follow-up Cancer Patients Attending a Palliative Care Outpatient Clinic in Saudi Arabia

Background:

Epidemiology of cancer-related nonpain symptoms receives less attention in literature as compared with cancer pain.

Objective:

This paper aims at exploring the prevalence and severity of nonpain symptoms in cancer patients attending a palliative care (PC) outpatient clinic.

Materials and Methods:

Over a 5 months period, consecutive adult cancer patients attending PC outpatient clinic at a tertiary hospital were evaluated for the presence and severity of 10 nonpain symptoms. Patients were grouped to new or follow-up cases and were also grouped according to performance status and cancer type. Prevalence and severity of symptoms were compared between groups using t test or analysis of variance as appropriate.

Results:

Fifty-one males and 73 females were interviewed. The most common cancer is female breast (27.4%) followed by head and neck (15.3%). Majority of patients (67%) were new to PC clinic. Patients had 5.1 nonpain symptoms on average, with most common symptoms being tiredness (79.8%), loss of appetite (71.8%), dry mouth (69.4%), anxiety (60.5%), and depression (50.8%). The least common symptoms were confusion and nausea (22.6% each). The median scores of severity were highest for tiredness, loss of appetite, dry mouth, and insomnia (5 points each). Symptoms were fewer among patients with good performance status (P = 0.002), whereas age, gender, cancer type, and encounter type were not associated with difference in symptom prevalence. Younger patients, females and those with poor performance status have shown a tendency toward higher severity scores for several symptoms.

Conclusion:

The significant prevalence and severity of nonpain symptoms among new and follow-up cancer patients seen in a PC outpatient clinic emphasizes the need for comprehensive assessment and routinely audited symptom management plans.     

TP53 genetic alterations in Arab breast cancer patients: Novel mutations, pattern and distribution

Breast cancer remains a worldwide public health concern. The incidence and mortality of breast cancer varies significantly in ethnically and geographically distinct populations. In the Kingdom of Saudi Arabia (KSA) breast cancer has shown an increase in incidence and is characterized by early onset and aggressiveness. The tumor suppressor TP53 gene is a crucial genetic factor that plays a significant role in breast carcinogenesis. Furthermore, studies have shown a correlation between certain p53 mutations and response to therapy in breast cancer. In the present study, TP53 mutations were identified by direct sequencing of the gene (exons 4-9) from 119 breast cancer tissues. The prevalence of TP53 mutations in Arab breast cancer patients living in the KSA is among the highest in the world (40%). Notably, 73% of the patients whose tumors harbored p53 mutations were less than 50 years of age. Furthermore, for the first time, we identified 7 novel mutations and 16 mutations in breast cancer tissues. Notably, all the novel point mutations were found in exon 4, wherein 29% of the mutations were localized. Furthermore, an excess of G:C→A:T transitions (49%) at non-CpG sites was noted, suggesting exposure to particular environmental carcinogens such as N-nitroso compounds. The results indicate that the TP53 gene plays a significant role in breast carcinogenesis and the early onset of the disease among Arab female individuals.     

Knowledge,Perception, and Attitudes of Cancer Patients Towards Cancer and Cancer Care: Local Perspective from Saudi Arabia

Understanding the attitudes of cancer patients towards different cancer-related issues is very important for the health care provider in order to deliver an optimal care. This survey was designed to collect data about the initial patient’s perception and reaction to the diagnosis of cancer, the patient’s preference regarding the disclosure of diagnosis, and prevalence and pattern of complementary and alternative medicine (CAM) use. Between January and December 2011, of 234 cancer patients, 42.2 % believed that eye of evil/envy was the cause of their cancers. In 18.3 % of cases, relatives refused to inform the patient about the diagnosis. Participants liked to be the first to be informed, either with relatives at the same time (44.21 %) or alone (33.48 %). Only 7.7 % of participants liked to totally leave decisions to their doctors and/or relatives. There were 53.4 % tried CAM before starting treatment, and 46.7 % continued using CAM during treatment and most of them used more than one type of CAM. Treatment with the Holy Qur’an or Ruqia was widely reported by the study population (92 %). Our survey confirmed that the patient’s preference is towards disclosure while the public attitude is, relatively, still against full disclosure. This situation poses a special challenge to the physicians in Kingdom of Saudi Arabia (KSA) when it comes to discussing the disease and treatment. Educational efforts are required to emphasize the curative role of conventional treatment, especially surgery, in many cases. Such efforts should also address the wrong beliefs and misconceptions regarding CAM.     

Long-term (up to 18 years) clinical and echocardiographic results of mitral balloon valvuloplasty in children in comparison with adult population

AIMS: The purpose of this study was to assess the safety, efficacy, and long-term results (up to 18 years) of mitral balloon valvuloplasty (MBV) in children in comparison to adults. METHODS: 57 children age < or = 18 years (group A) and 474 adult patients (group B) who underwent successful MBV and were followed up for a mean 8.5 +/- 4.8 (range 1.5-18) years were analyzed. RESULTS: Patients in group A had a lower mitral echocardiographic score (echo score), 7.6 +/- 1.3 vs. 8.1 +/- 1 (P = 0.0005); smaller Doppler mitral valve area (MVA), 0.82 +/- 0.16 cm(2) vs. 0.92 +/- 0.17 cm(2) (P < 0.0001); and higher mitral valve gradient, 15.2 +/- 2.3 mmHg vs. 14.3 +/- 2.1 mmHg (P = 0.0003), than group B. Immediately after MBV, group A had larger MVA whether measured by catheter, 1.99 +/- 0.57 cm(2) vs. 1.8 +/- 0.52 cm(2) (P < 0.001), or by Doppler, 2.0 +/- 0.27 cm(2) vs. 1.97 +/- 0.28 cm(2) (P < 0.01), and similar complication rates, compared to group B. After a mean follow-up of 8.5 +/- 4.8 (range 1.5-18 years), restenosis in group A was 26% vs. 31% for group B (P = 0.41). Echo score > 8 (P = 0.046) was a predictor of restenosis in children and echo score > 8 (P < 0.0001) and previous surgery (P = 0.043) were predictors of restenosis in adults. Actuarial freedom from restenosis at 10, 15, and 18 years for groups A and B were 78%+/- 7%, 64%+/- 9%, and 18%+/- 14% and 77%+/- 2%, 43%+/- 4%, and 17%+/- 4%, respectively (P = 0.26). Event-free survival rates at 10, 15, and 18 years were 87%+/- 6%, 62%+/- 1%, and 20%+/- 2% versus 87%+/- 1%, 51%+/- 4%, and 20%+/- 5% for groups A and B, respectively (P = 0.51). Postprocedure MVA < 2.0 cm(2) (P = 0.043) and previous surgery (P = 0.03) were identified as predictors of events in children. Echo score > 8 (P < 0.0001) and prevalvuloplasty AF (P = 0.03) were identified as predictors of events in adults. CONCLUSION: MBV is safe and effective in children with rheumatic MS. It provides better immediate results than in adults and excellent long-term results that are comparable to those seen in adults.     

Impact of C1q deficiency on the severity and outcome of childhood systemic lupus erythematosus

Objective: To delineate the clinical and laboratory features of systemic lupus erythematosus (SLE) in C1q‐deficient Saudi children and to compare them with sporadic SLE patients with respect to their clinical and laboratory features and disease outcome. Methods: The C1q‐deficient SLE patient group comprised 14 patients, while the comparative group comprised 11 patients selected by systemic sampling from our pediatric lupus clinic database. The two groups were compared with respect to: demographic, clinical and laboratory variables and outcome. Results: The C1q‐deficient SLE patients had an earlier age of onset of disease (P = 0.003); 43% had familial SLE and none of the comparative group had family histories of SLE. The two groups were comparable with respect to gender, disease duration and follow‐up. Scarring alopecia, discoid rash and nail changes were more frequent in the C1q‐deficient SLE patient group. However, there were no significant differences. The mean white blood cell count was lower (P = 0.04) and the level of anti‐Sm and anti‐phospholipid antibodies were higher (P = 0.04) in the C1q‐deficient SLE patients. Other variables did not show significant differences. Two patients from the C1q‐deficient SLE patient group died due to infection. All patients from the control group are alive. Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index mean was higher in the C1q‐deficient SLE patients group but was not statistically significant. Conclusion: C1q‐deficient SLE patients tend to be younger and more likely to have familial disease with severe cutaneous manifestations. The mortality among them is more frequent, which may reflect disease severity.