Statin associated hepatic adverse effects: a retrospective review from a regional hospital in sultanate of Oman

This study aimed to evaluate the prevalence, pattern and predisposing factors for hepatic adverse effects with statins in a regional hospital in Sultanate of Oman. A retrospective review of the patient files in Department of Medicine during the year 2011 was done to evaluate any hepatic dysfunction possibly related to statins among the patients. For each case of suspected statin induced hepatic effect, additional details on temporal relationship, pattern of presentation, management, final outcome and any contributing factors were obtained. Difference in the occurrence of hepatic effects based on the patient demographics and drug characteristics was additionally evaluated. A total of 927 patients meeting the inclusion criteria were included for the study. Mean age of the evaluated patients was 63.1 + 11.37 and median duration of use of statin in months was 22 [IQR, 43.25]. In 40 [4%] of the 927 patients, there was presence of a hepatic effect considered to be statin related and only in 12 [1%] patients a significant transaminase rise [>3 times] was observed. Median duration of use of statin among those patients who developed suspected statin induced hepatic effects and those who did not was 45 [IQR,52] and 21 [IQR, 43] months, respectively and the difference observed was statistically significant. A significant difference in the prevalence of hepatic effects was observed only based on the duration of statin use. There was an infrequent occurrence of significant hepatic effects associated with statins in the study population. Our results support the latest recommendations including from United States Federal Drug Administration [US PDA] that statins appear to be associated with a very low risk of serious liver injury and that routine periodic monitoring of transaminases does not appear to detect or prevent serious liver injury in association with statins use

Promoter region polymorphism [174 G/C] of interleukin-6 gene and SLE; are they associated?

SLE is a systemic autoimmune disease with polyclonal B cell hyperactivity, spontaneous lymphocyte proliferation, and the production of pathogenic antibodies to self-antigens. Interleukin-6 is a pleiotropic cytokine with diverse functions including B-cell growth and differentiation. IL-6 levels have been shown to be affected by single nucleotide change from G to C at position -174 in the promoter region of the IL-6 gene.To find out whether single nucleotide polymorphisms in the promoter region of the IL-6 gene [-174 G/C] constitute a genetic susceptibility for SLE and its association with various disease clinical and immunological features. Forty-two female SLE patients and 40 healthy controls were genotyped for IL-6 gene promoter region [-174 G/C] polymorphism using PCR. SLE patients satisfied the 1982 revised criteria of the American Rheumatism Association for the classification of SLE, with a mean age of 32.4 +/- 5.5 years and mean disease duration of 5.7 +/- 1.5 years. The healthy controls were matched for age and sex, with a mean age of 31.7 +/- 4.9 years. All subjects were recruited from the Rheumatology and Rehabilitation and Internal Medicine Departments, Kasr El Aini Hospitals. SLE clinical and laboratory features were recorded including constitutional, hematological, joint, renal, and neuropsychiatric manifestations, oral ulcers, serositis, malar rash, and photosensitivity and CBC, liver, kidney functions and serum C3 and C4 levels. Positivity for ANAs, Anti-dsDNA and Anti-Sm antibodies were determined. Genotypic and allelic distributions showed no significant differences between SLE patients and controls. The frequency of G allele was higher than C allele in both patients [83.3% vs. 16.7%] and controls [85% vs. 15%]. SLE patients with GG genotype showed significantly higher frequencies and increased risk of; constitutional manifestations at disease onset [P = 0.02], OR [95% CI] = 6.55 [1.22-35.12], photosensitivity [P = 0.03], OR [95% CI] = 4.67 [1.11-19.54], hematological disorders [P = 0.02], OR [95% CI] = 5.5 [1.29-23.39] and positivity of ANAs and Anti-dsDNA [P = 0.046, 0.03: OR [95% CI] = 7 [1.1-45.44], 6.43 [1.23-33.65], respectively]. Furthermore, those patients had significantly lower mean WBCs counts when compared to SLE patients with [GC and CC] genotypes [4.54 +/- 1.31 vs. 5.98 +/- 1.04/dl, P = 0.002]. Twenty-five patients had lupus nephritis [LN] proved by renal biopsy but none of them had CC genotype. LN patients with GG genotype had nearly similar mean 24-h proteinuria to those with GC genotype [2.93 +/- 1.07 vs. 2.68 +/- 1.06 g/24 h and P = 0.39]. No significant difference was found in IL-6 genotype and allele distributions when patients with diffuse proliferative glomerulonephritis [class IV], which has the worst prognostic outcome, were compared to patients with non-class IV glomerulonephritis [classes II and III] [P = 0.12, 0.15, respectively]. IL-6 promoter region [-174 G/C] polymorphism does not confer susceptibility to SLE but it is related to the presence of distinct clinical and immunological features. Furthermore, the increased frequency of the high-response G allele suggests that a genetically determined high IL-6 response may have a pathogenic role

Methylenetetrahydrofolate reductase gene is determinant of hyperhomocysteinemia in epileptic patients

Recent evidences mount that homocysteine level significantly increased in epileptic patients particularly those taking anticonvulsant drugs. Several previous studies revealed that a 677C T transition in the methylenetetrahydrofolate reductase [MTHFR] gene is related to Hyperhomocysteinemia and might increase risk of vascular occlusive pathology. However other publications negate this relationship. This study aimed to determine the prevalence of hyperhomocysteinemia, [MTHFR] gene 677C [right arrow] T mutations and whether this mutation is related to elevated homocysteine concentrations in epileptic patients and to determine the possible relationship between clinical data with elevated Hcy levels and genetic mutations. Twenty five epileptic patients [13 males, 12 females], their mean age is 15.08 +/- 13.7 divided into two groups according to medications: Group 1: Newly diagnosed patients who did not receive medications yet. They were 16 patients, Group 2: Patients who received valproate. They were 9 patients. Fifteen healthy sex- and age-matched controls were recruited. After through neurological evaluation and EEG study, plasma total homocysteine [tHcy] level was determined by specific immunoassays [IMX, Abbott Laboratories]. MTHFR 677 C[right arrow]T mutation using a polymerase chain reaction [PCR] and restriction fragment length polymorphism analysis with HinfI digestion were investigated. The prevalence of hyperhomocysteinemia [>/= 11.4micromol/L, 90[th] percentile of control group] was significantly higher in the epileptic patients than in the controls [15 patients [60%] V one volunteer [6.6%] p<0.05]. The mean of homocysteine level was significantly higher in the epileptic patients than in the controls [10.23 +/- 5.9 V 5.35 +/- 1.64, p<0.05]. No significant correlation was found between clinical data [Age, sex, age of onset, seizure type, seizure frequency, duration and valproate medication] and homocysteine level. The homozygosity for the 677 C[right arrow]>T mutation of MTHFR was associated with elevated tHcy levels. The magnitude of hyperhomocysteinemia in MTHFR CT heterozygotes was more pronounced in epileptic patients than in controls [12.64 +/- 6.64 V 7.9 +/- 2.54 micromol/L, p<0.05]. Statistically significant differences is noticed between hetero mutant patients and patients with normal gene as regard mean homocysteine level [12.64 +/- 6.64 V 8.50 +/- 4.68 in p value <0.01]. The epileptic patients are at a higher risk of hyperhomocysteinemia. The C677T mutation in MTHFR gene contributes to hyperhomocysteinemia in epileptic patients. So measuring homocysteine in epileptic patients is recommended as early management of hyperhomocysteinemia help to avoid its devastating consequences

Comparison of bone density of femoral neck and spine in interstitial lung disease and chronic obstructive pulmonary disease

To determine bone mineral density [BMD] of femoral neck and spine in Interstitial Lung Disease [ILD] and chronic obstructive pulmonary disease [COPD] to avoid fractures at those points. The study was conducted on seventy patients complaining of low back pain and pain related to hip joint. Their mean age was 39 +/- 7 years. They were subjected to full history taking, physical examination, pulmonary function tests [PFT], plain chest X-ray and routine laboratory investigations. According to PFT, patients were grouped into patients with obstructive pattern and patients with restrictive pattern, taking steroids or not. They were all examined with dual energy X-ray absorptiometry [DXA]. Twenty-five patients on oral steroids showed femoral osteopenia 32% and osteoporosis 48%. Twenty-five patients on inhaled steroids showed osteopenia 48%, osteoporosis 12%. Twenty patients taking no steroids showed 7% osteoporosis, no osteopenia. As regard spine DXA, patients on oral steroids showed 40%, osteopenia, 12%, and osteoporosis. Those on inhaled steroids showed 32% osteopenia, 4% osteoporosis. Patients taking no steroids showed 25% osteopenia. In patients taking oral or inhaled steroids, there was no significant difference between total femur and spine density with DXA [p=0.177 for oral and p=0.112 for inhaled steroids]. However, there was significant difference between femoral neck and spine density with DXA [p=0.002 for oral, p=0.000 for inhaled steroids]. Obstructive or restrictive lung disease patients have low bone mineral density, significantly more in those under steroid therapy, especially femoral neck. DXA neck femur could be a screening test for such patients on steroid therapy

Platelet derived growth factor and the extent of skin thickening as potential indicators of pulmonary affection in systemic sclerosis

Systemic sclerosis is a multisystem disease that has considerable variability in its presentation, course, and prognosis. The aim of this study was to determine serum levels of platelet-derived growth factor [PDGF A/B] in patients with systemic sclerosis [SSc] and to correlate these levels with the extent of skin sclerosis and presence of pulmonary affection. Moreover, the efficiency of PDGF and skin score in early detection of pulmonary affection were assessed. The study included 22 female patients with SSc [according to the American College of Rheumatology] [Masi et al., 1980] and 15 age-matched healthy control females. According to the classification by LeRoy et al. [1988], we divided our patients into limited SSc [10 patients-45.5%] and diffuse SSc [12 patients-54.5%]. The extent of skin sclerosis was assessed by the modified Rodnan total skin thickness scoring [TSS] system [Clements et al., 1995]. In our study, patients with limited SSc had a skin score <25, while those with diffuse SSc had skin score >25. Five diffuse SSc patients had associated pulmonary affection, diagnosed by history taking, clinical examination, chest x-ray, arterial blood gases, spirometry and diffusing capacity of the lung for carbon monoxide [DLCO]. Serum levels of PPGF were determined in SSc patients and healthy controls using quantitative sandwich ELISA technique. Serum PDGF mean and standard deviation in healthy subjects was 5.2 +/- 2.466 ug/l. PDGF values showed continuous significant increment with progression of the disease. Mean PDGF serum levels in limited SSc, diffuse SSc without pulmonary affection and with pulmonary affection were 15.8 +/- 2.3, 20.86 +/- 2.41 and 32 +/- 3.08 ug/l, respectively. Furthermore, the results revealed that PDGF value <10 ugh, tend to exclude the diagnosis of SSc with 100% sensitivity and specificity, respectively. Moreover, all patients with diffuse SSc and having pulmonary affection had PDGF values >25 ug/l. This value provided a diagnostic sensitivity and specificity of 100%. As regards the total skin score, a statistical significance was found between limited and diffuse SSc but did not show a statistically significant difference between SSc patients with [32.2 +/- 4.49] and without [29.71 +/- 3.25] pulmonary affection [p>0.05]. However, in patients with diffuse SSc, PDGF levels tended to correlate positively with the skin score [p=0.05]. ROC plot showed that skin score at a value of 29 was the best cut-off level to diagnose pulmonary affection in patients with diffuse SSc with a diagnostic sensitivity of 80% and specificity of 71.4%. PDGF is a simple and easy laboratory test that tends to exclude the presence of SSc at a cut-off value of 10ng/ml with 100% sensitivity and specificity, respectively. PDGF correlates positively with extent of skin involvement and significantly with pulmonary affection. PDGF and skin scoring system are simple laboratory and physical measures for evaluating patients with systemic sclerosis with cut-off levels of 25 ug/l, and 29 respectively in detecting pulmonary affection. However, further studies are recommended on larger population to ensure the diagnostic efficiency of PDGF and to test the applicability of our obtained cut-off values

Renal function reserve in chronic obstructive pulmonary disease with type II respiratory failure

Increase in renal blood flow in response to certain stimuli such as dopamine infusion, oral protein load, and amino acid infusion. Reduced or absent renal functional reserve [RFR] is an early index of renal impairment. Our work studies the [RFR] in Chronic Obstructive Pulmonary Disease [COPD] patients with chronic compensated type II respiratory failure. Our study included 15 COPD patients with compensated type II respiratory failure and 5 normal controls. The patient group had mean Pa O[2] 56.5 +/- 6.4 and Pa CO[2] 56.5 +/- 3.2, while in normal controls the mean Pa 02 was 97.4 +/- o.3 and Pa CO[2] was 42.3 +/- 1.2. Hypoxic patients [Pa O[2]< or =59mm Hg] allowed to receive low flow oxygen by nasal prongs to keep their Pa O[2] >or = 60 mm Hg and Sa O[2] > or = 90% without rise of Pa CO[2] within 2 hours before and during the study. The pulsatility index [PI], an index of reno-vascular resistance [RVR], was measured non invasively by Doppler Ultrasonograghy at baseline and 20 minutes after infusion of dopamine in diuretic dose. The baseline PT was nearly similar in the control group and in COPD patients [no significant difference], the PI fell significantly in the control group after dopamine infusion from 1.03 +/- 0.14 to 0.83 +/- 0.1[P< 0.05], but increased significantly in COPD patients from 1.02 +/- 0.12 tol.18 +/- 0.13 [P<0.05] after dopamine infusion. Renal functional reserve is impaired in hypercapnic COPD patients and this may be a factor in the development of edema frequently seen in these patients

Study on the oxidant and antioxidant status in vitiligo patients

The aetiology of vitiligo is still unknown. Several hypotheses have been proposed to explain vitiligo: genetic neural, immunological, self destructive, convergence hypothesis and oxidative stress hypothesis. The current study is concerned with the oxidative stress hypothesis and how oxidants and antioxidants affect the pathogenesis of vitiligo. So, our aim is to determine the role of malondialdehyde and glutathione in the pathogenesis of vitiligo. The amount of malondialdehyde [oxidant] and glutathione [antioxidant] were measured in serum and in skin tissue in 30 vitiligo cases and 20 healthy controls. The study showed significant changes between patients and controls in glutathione level in blood and tissue samples. Also there were significant changes between patients and controls in malondialdehyde in blood and in tissue samples favoring that glutathione and malondialdehyde play a role in the pathogenesis of vitiligo

Hepatocyte growth factor in serum and bronchoalveolar lavage fluid versus exhaled nitric oxide in systemic lupus erythematosus

The present study tried to evaluate the clinical significance of hepatocyte growth factor [HGF] in the serum and bronchoalveolar lavage fluid [BALF] in systemic lupus erythematosus [SLE] patients and their relation to nitric oxide [NO] in exhaled air. Forty SLE patients were investigated along with ten apparently healthy individuals. The patients' group was divided into two groups: group [A] Inactive SLE patients without pulmonary affection [n=14] and group [B] SLE patients with pulmonary affection [n=26]. The last group was further classified into 4 sub groups: - B1= Active SLE patients without interstitial lung disease [ILD], B2= Active SLE patients with interstitial lung disease + Alveolitis [ILD +A], B3: Inactive SLE patients without ILD and B4= Inactive - SLE patients with ILD. All patient and control groups were evaluated for chest X-ray, pulmonary function tests and high-resolution computerized tomography [HRCT], along with systemic lupus erythematosus [SLE routine laboratory investigations. Measurement of HGF Levels in serum and BALF by Immunoassay and exhaled nitric oxide [NO] was measured by chemiluminescence. There were abnormal pulmonary function tests in 65% [26/40] of SLE patients and abnormal HRCT in the form of ILD in 32.5[13/40] of SLE patients. The exhaled NO showed a significant elevation in patients with activity especially those with evidence of active inflammation of the lung. There was no significant elevation of exhaled NO for patients with ILD without evidence of active inflammation. The level of HGF in serum and BALF showed a significant elevation in patients with activity especially with the presence of active lung inflammation. Also, there was a significant elevation of serum HGF and BALF-HGF for patients with ILD without evidence of inflammation. The level of HGF in serum and BALF showed significant elevation in patients as compared with control subjects. HGF levels in BALF of patients was more elevated than HGF levels in serum of patients groups. HGF in serum and BALF was increased in patients with pulmonary fibrosis and correlated with clinical parameters. Measurement of exhaled NO is a simple and non-invasive method to detect the presence of inflammatory lung disease

Directigen Flu A + B test versus viral culture and reverse transcription-PCR for diagnosis of influenza virus type A and type B

In our study, 60 sputum specimens were collected from patients suffering from upper and lower respiratory tract manifestations with a mean age of 44.5 years. Out of the 60 patients, 49 patients had developed pneumonia as a complication. In addition to 20 specimens were collected from apparently healthy subjects matching in age with the patient group. All specimens were subjected to Directigen Flu A+B assay, viral culture on Madin Darby canine kidney cell and reverse transcription-PCR [RT-PCR] for demonstration of influenza type A and B. Directigen Flu test had a detection rate of 18.3% for influenza type A and 26.6% for influenza B. Viral culture had a detection rate of 20% and 26.6% for influenza type A and influenza type B respectively. While RT-PCR had a detection rate of 16.6% and 25% for influenza virus type A and B respectively. The sensitivity, specificity and positive and negative predictive value was[66%, 0%, 72.7%, 0% for influenza A virus and 75%, 0%, 75%, 0% for influenza type B by Directigen Flu A + B test. While the resolved sensitivity, specificity and positive and negative predictive value of RT-PCR was 100%, 83.3%, 100%, 60% for influenza A virus and 100%, 93.7%, 100%, 80% for influenza type B. Directigen Flu test is rapid, easy, reliable test that can be used for diagnosis and discrimination between influenza type A and type B infections. But it lacks specificity in some patients, thus, it requires confirmation by tissue culture and RT-PCR to rule out false-positive results