Accuracy of non-fasting lipid profile for the assessment of lipoprotein coronary risk

Objective: To determine the diagnostic accuracy of non-fasting lipid profile in the diagnosis of hyperlipidemia, taking fasting lipid profile as gold standard, in adult population

Study Design: Cross-sectional validation study

Place and Duration of Study: Department of Chemical Pathology and Endocrinology, Armed Forces Institute of Pathology, Rawalpindi, from July to December 2014

Methodology: One hundred seventy-five adult patients coming for fasting lipid profile were included; their non-fasting samples were taken on the next day. Patients on anti-cholesterol treatment and indoor patients were excluded. Total cholesterol [TC], high density lipoprotein-cholestrol [HDL-C], and triglycerides were measured by direct enzymatic colorimetric method by Modular p-800[registered]. Low density lipoprotein-cholesterol [LDL-C] was calculated by Friedewald's formula, but when triglyceride was greater than 4.5 mmol/l, then LDL-C was measured directly by homogenous enzymatic colorimetric method. Non-HDL-C was calculated by simple equation, i.e. TC-HDL-C

Results: Non-fasting lipid profile had 93% specificity, 51% sensitivity, 94% positive predictive value and 49% negative predictive value; and 65% accuracy with 7.28 positive likelihood ratio and 0.52 negative likelihood ratio. Non-fasting TC and non-HDL-C were significantly higher than fasting TC and non-HDL-C by mean difference of 0.2 mmol/l each with p=0.001 and p=0.004, respectively. Fasting and non fasting HDL-C are comparable to each other with mean difference of 0.01 mmol/l [p=0.745]. Receiver operating curve [ROC] of non-fasting non-HDL-C showed 0.804 [95%CI [0.738-0.870], [p=0.000] area under the curve [AUC] indicating that it was a significant test for ruling out hyperlipidemia. Bland-Altmann plot showed a significant difference between non-fasting, non-HDL-C and fasting LDL-C and non-fasting, non-HDL-C -0.087540 with bias -0.00109; therefore, these cannot be alternative to each other

Conclusion: Diagnostic accuracy of non-fasting lipid profile was found significantly higher than fasting lipid profile [p=0.004] for the assessment of lipoprotein coronary risk on the basis of non-HDL-C, which seemed to be significant test for ruling out hyperlipidemia

Impact of CYP2C9 genetic polymorphism on warfarin dose requirements in Pakistani population

Variations of cytochrome-P450 enzyme system [CYP2CP] are associated with impaired metabolism of warfarin. The objective of our study was to estimate the frequency of genetic and allelic variants of CYP2C9 in Punjabi population of Pakistan and their effects on warfarin dose requirement. One hundred and twenty unrelated Pakistani subjects belong to Punjab province, were randomly included from the registry of National Institute of Heart Disease Rawalpindi, Pakistan. The patients had stable international normalized ratio [INR] of 2 to 3 for last 3 months with warfarin therapy after heart valves replacement. The detection of CYP2C9 variant was done on polymerase chain reaction-restriction fragment length polymorphism [PCR-RFLP] assay. Total 120 patients [73 males; 47 females] of mean age of 37 years participated in the study. Nine patients had mutant allele CYP2C9*3 [7.5%], one CYP2C9*2 [0.8%] and 110 patients exhibited wild type CYP2C9*1 [91.7%]. The frequency of CYP2C9 genotype was *1/*1 [0.858] ; *1/*3 [0.117] ; 2/*20 [0.08] and *3/*3 [0.017] in our study population. A high dose of warfarin [42.2 +/- 9.56] mg/week is required for patients with *1/*1 genotype as compared to patients with *2/*2 [17.5 +/- 1.9] and *1/*3 [16.6 +/- 2.3] allele [p<0.001]. Individuals with CYP2C9*3/3* need lowest [8.75 +/- 1.76 mg/week] daily warfarin dose. In conclusion, the genetic variations in the CYP2C9 occur in 14% of Punjabi ethnic group in Pakistan. Presence of CYP2C9*2 or *3 variants is an independent predictor of low warfarin dose requirement in our patients. CYP2C9 variants assay may be used in high risk groups for appropriate dose adjustment to avoid complications on long term basis

Correlation of steatosis with fibrosis and necro-inflammation in chronic hepatitis C infection in the absence of confounding factors

To assess the frequency and degree of hepatic steatosis in patients of chronic hepatitis C infection and determine its correlation with stages of fibrosis and necro-inflammatory grades. Cross-sectional study. The study was carried out in the Department of Pathology [Histopathology], Army Medical College, Rawalpindi, from March 2006 to March 2007. Patients who had undergone a liver biopsy for evaluation of hepatitis C virus infection were included in the study. Demographic characteristics and laboratory data were collected at the time of biopsy. First hundred biopsy specimens meeting the inclusion criteria were assessed for steatosis, necro-inflammation and fibrosis. Steatosis was present in 46 patients and graded as mild [41.3%], moderate [54.3%] and severe [4.3%]. An overall significant correlation was found between grades of steatosis with stage of fibrosis [p < 0.0001] but no correlation was found with necro-inflammatory grades. Only focal necrosis revealed weak correlation with grades of steatosis [p < 0.003]. These results suggest a possible role of the hepatitis C virus itself in the pathogenesis of steatosis and indicate its close relationship with fibrosis and focal degeneration in chronic hepatitis C. Necro-inflammation seen in liver biopsy is host immune reaction to hepatitis C virus and is not related to steatosis

Effects of combined interferon alpha and ribavirin therapy on thyroid functions in patients with chronic hepatitis C

To determine the frequency of thyroid dysfunction in patients of chronic hepatitis C during treatment with interferon alpha-2b and ribavirin therapy. A cohort study. Army Medical College and Military Hospital, Rawalpindi, from February 2006 to January 2007. One hundred and sixty seven non-cirrhotic chronic hepatitis C patients were grouped into treatment group [n=107] and control group [n=60] awaiting treatment. Baseline serum[s.] Alanine Transferase [ALT] and S. Aspartate Transferase [AST] were measured by IFCC method. Serum Thyroid Stimulating Hormone [S. TSH], serum free thyroxine [S. Free T4] and serum total triiodothyronine [S.T3] level were determined by chemiluminescence. Study group patients underwent 24 weeks IFN and ribavirin therapy and were followed-up for thyroid dysfunction at weeks 0, 12 and 24. Control group patients underwent the same tests at weeks 0, 12 and 24. Statistical analysis was done on SPSS 15. Out of 107 patients of treatment group, 20 patients [18.69%] developed thyroid dysfunction. Females were at higher risk with Relative Risk [RR] of 11.25 and Attributable Risk [AR] of 91%. Hypothyroidism was more common than hyperthyroidism. Interferon-alpha and ribavirin therapy induces thyroid dysfunction in chronic hepatitis C patients. Hypothyroidism was more common. Females are at a higher risk of developing thyroid dysfunction

Comparison of serum procalcitonin and c-reactive protein in diagnosis of bacterial meningitis

The diagnostic accuracy of Procalcitonin [PCT] as compared with C - reactive protein [CRP] for early diagnosis of bacterial meningitis in children was evaluated. Descriptive diagnostic study. This study was conducted in Pathology department of Army Medical College Rawalpindi from September 2007 to September 2008. Descriptive diagnostic accuracy study was conducted in Pathology Department of the Army Medical College, Rawalpindi. Total 77 subjects consisted of 31 patients of bacterial meningitis and 46 healthy children were included as controls from the Military hospital, Rawalpindi. The patients comprised of 18 [58%] male and 13 [42%] female with mean age 6 years. Patient's investigations including cerebrospinal fluid [CSF] examination and culture were carried out at admission. PCT and CRP were analyzed on Vidas analyzer and Immulite 1000 respectively. PCT levels were significantly high median [range] of 4.5 ng/ml [0.10-19.00] ng/ml than controls 0.45 ng/ml [0.10-3.00]. Serum CRP levels were moderately elevated with median [range] 11 mg /L [0.30 - 23.00] as compared with 0.30 mg/L [0.30-9.5] controls. The Area under receiver characteristic curve of PCT 0.86 [95% CI: 0.76-0.93] was significantly higher than CRP 0.72 [95% CI: 0.61-0.82]. The optimum diagnostic cutoff point for PCT and CRP were 2 ng/ ml and 6 mg/L respectively by ROC analysis. PCT had maximum sensitivity 74% and specificity 84% at cutoff > 2 ng/ ml while CRP revealed sensitivity 58% and specificity 83% at cutoff > 6mg/ L. This study has demonstrated PCT as a more reliable diagnostic marker than CRP for early diagnosis of bacterial meningitis and can be used in combination with clinical evaluation for proper management of the seriously ill children

Evaluation of diagnostic accuracy of APRI for prediction of fibrosis in hepatitis C patients

Several non-invasive markers are being used to assess the structural liver damage in patients with chronic hepatitis C [CHC]. We evaluated Aspartate aminotransferase [AST] to platelet ratio index [APRI] in comparison with Metavir scoring for assessing the severity of hepatic fibrosis in the CHC patients in district Rawalpindi. One hundred twenty CHC patients, naive for HCV treatment, underwent liver biopsy in tertiary care hospitals of district Rawalpindi, participated in the study. Liver biopsies were reviewed by Metavir scoring system. Serum AST was analyzed by IFCC method. Platelets were measured on a haematology Analyzer. Patients with mild fibrosis [F0, F1] were differentiated from significant fibrosis [F2, F3, F4] and those with mild/moderate fibrosis [F0, F1, F2] from advanced fibrosis [F3, F4] based on APRI score as compared to liver biopsy. Liver biopsies examination revealed that out of 120 patients 10 [8.3%] had no fibrosis [F0], 46 [38%] portal fibrosis [F1], 34 [28%] septal fibrosis [F2], 21 [18%] bridging fibrosis [F3] and 9 [8%] cirrhosis [F4]. APRI correctly classified 58 [48%] patients of significant fibrosis with AUC=0.82 [95% CI, 0.73-0.88] at cut-off 0.5 and 1.5 with negative predictive value [NPV], Positive predictive value [PPV], sensitivity and specificity of 78%, 72%, 66%, 83% and 58%, 90%, 41% and 90% respectively. Eighty-seven [66%] CHC patients were correctly classified for advanced fibrosis with AUC=0.87[95%CI 0.79-0.94] at cutoffs 0.90 and 1.75 with a 95%NPV at 0.90 and 78% PPV at 1.75. APRI could correctly identify significant fibrosis in 48% and advanced fibrosis in 66% cases with acceptable degree of diagnostic accuracy in CHC patients in our clinical practice

Assessment of lipid dysfunction in patients on maintenance haemodialysis

Dyslipidaemia is a major risk factor of cardiovascular disease in patients on maintenance haemodialysis. Both increased and decreased levels of cholesterol are associated with increased cardiovascular mortality in haemodialysis patients. To assess the lipid dysfunction among patients on maintenance haemodialysis in a nephrology unit at Rawalpindi as compared with healthy individuals. A descriptive comparative study was carried out in a nephrology unit at Rawalpindi, Pakistan. A total of 140 subjects were included consisting of 70 patients on maintenance haemodialysis [MHD] and 70 healthy controls. Body mass index [BMI] was measured according to WHO guidelines. Serum total cholesterol [TC], triglycerides [TG] and high-density lipoprotein cholesterol [HDL-C] were assayed on chemistry analyser. Low-density lipoprotein cholesterol [LDL-C] was calculated by Friedwald equation. MHD patients had significantly lower BMI, mean [SD] 20.07[3.66] as compared with the controls 22.88[3.97] kg/m2 [p < 0.001]. The lipid profile among MHD patients and controls are given as mean [SD]: [a] Total Cholesterol 3.84[1.06] vs 4.65[0.97] [p < 0.001], [b] LDL-C 2.21[0.77] vs 2.93[0.71] [p < 0.001], [c] HDL-C 0.95[0.166] vs 0.97[0.138] [p=NS], [d] Non HDL 2.88[0.95] vs 3.67[0.88] [p < 0.0001], [e] Triglycerides 1.68[1.09] vs 1.69[0.86] [p=NS]. The most common abnormality observed in haemodialysis patients was low HDL-C [81%] followed by increased Non-HDL-C [23%] and increased serum triglycerides [19%]. It is concluded that our patients on maintenance haemodialysis have significantly low BMI, total Cholesterol, LDL-C and Non-HDL-C depicting malnutrition leading to inflammation, accelerated atherosclerosis process and cardiovascular complications

Estimation of ionized calcium, total calcium and albumin corrected calcium for the diagnosis of hypercalcaemia of malignancy

To measure levels of ionized calcium, total calcium and albumin corrected calcium in patients with different malignant disorders for the diagnosis of hypercalcaemia of malignancy. A case control comparative study. The study was carried out in the Department of Pathology, Army Medical College Rawalpindi, Armed Forces Institute of Pathology and Department of Oncology CMH, Rawalpindi from March 2003 to December 2003. Ninetyseven patients of various malignant disorders, admitted in the Department of Oncology, CMH, Rawalpindi, and 39 age and gender-matched disease-free persons [as control] were included in the study. Blood ionized calcium [Ca++], pH, sodium [Na+] and potassium [K+] were analysed by Ion selective electrode [ISE] on Easylyte[R] auto analyser. Other related parameters were measured by colourimetric methods. Blood Ca++ levels in patients suffering from malignant disorders were found significantly high [mean +/- SD: 1.30+017 mmol/L] as compared to control subjects [mean +/- SD: 1.23+0.03 mmol/L] [p<0.001]. The number of patients with hypercalcaemia of malignancy detected by Ca++ estimation was significantly higher [38%] as compared to total calcium [8.4%] and albumin corrected calcium ACC [10.6%] [p<0.001]. There was no statistically significant difference in other parameters e.g. phosphate, urea, creatinine, pH, Na+ and K+ levels in study subjects and controls. Detection of hypercalcaemia can be markedly improved if ionized calcium estimation is used in patients with malignant disorders

Significance of bone marrow Trephine biopsy in the diagnosis of haematological and non-haematological disorders

To evaluate the frequency and document the histological pattern of various haematologic and non 'haematologic malignancies and infections, which can be diagnosed by Bone marrow trephine biopsy. A retrospective, cross sectional study was carried out at Histopathology department of Army Medical College Rawalpindi from January 2000 to December 2004. The bone marrow trephine biopsies were taken with Jamshidi's - type needle. The tissues were fixed in 10% formal- saline and then decalcified in 5% nitric acid. These were processed under standard conditions. A total of 789 cases with age range of 9 years to 75 years were studied during a period of five years. Majority of the cases showed male preponderance [69.83%] as compared to females [30.16%]. The most common histological findings in order of frequency were reactive changes [22.43%], unremarkable marrow [16.09%], inadequate biopsy [9.63%], megaloblastic anaemia [7.73%], acute leukaemia [6.21%], erythroid hyperplasia [5.95%]. The less common lesions were multiple myeloma [3.92%], lymphoproliferative disorders [3.80%], hypoplastic marrow [3.54%], chronic granulomatous inflammation [2.53%] and myelofibrosis [2.40%]. The miscellaneous group [5.70%] comprises rare diseases. Bone marrow trephine biopsy is a valuable diagnostic tool in the diagnosis of various types of infections and hematologic and non'hematologic malignancies. Majority of our patients showed reactive changes followed by acute leukaemia and erythroid hyperplasia. It has also been proved useful in detecting micrometastases when primary is not known with the other available diagnostic modalities

Neonatal cholestasis Syndrome: an experience at Army medical college and Military Hospital Rawalpindi

To find the causes of neonatal cholestasis in our set up and to see the role of liver biopsy in differentiating neonatal hepatitis from biliary atresia. Design: A cross sectional survey. Place and duration of study: Histopathology department of Army Medical College and Military Hospital Rawalpindi from January 2000 to December 2004. Patients and A total of 62 cases were studied with age range of 1.5 months to 5 years. The subjects selected for biopsy were children with persistent jaundice and hepatosplenomegaly. The biopsy was taken with the help of Surecut needle under the cover of diluted intravenous Ketamine. The fixed tissues were processed under standard conditions. Result: Majority of the patients [62.90%] were of biliary atresia followed by neonatal hepatitis [27.42%]. Paucity of bile ductules was seen in 3 cases while three patients were of indeterminate etiology. Cirrhosis of liver was noted in 10 patients; six because of biliary atresia and two cases each of alpha-1 antitrypsin deficiency and galactosemia. Amongst neonatal hepatitis cases most of the patients were idiopathic in nature [58.82%]. In our set up, biliary atresia is an important and main cause of neonatal cholestasis and liver biopsy is a valuable diagnostic tool in differentiating biliary atresia from neonatal hepatitis

Monitoring of progression in diabetic nephropathy by use of protein: Creatinine index

To assess the progression of nephropathy in diabetic patients by using protein: creatinine index in spot urine sample as compared to 24 hours urinary protein excretion rate. Comparative cross-sectional study. One hundred and fourteen patients, 45 male and 69 female, aged 18 to 67 years having proteinuria of more than 150 mg/day were included this study. Quantitative measurement of protein in the spot and 24h urine specimens were carried out by a method based on the formation of a red complex of protein with pyrogallal red in acidic medium, on Microlab 200 [R] [Merck]. Estimation of creatinine was done on Selectra [R]-2 [Merck] by Jaffe's reaction. The urine protein: creatinine index was calculated by dividing the urine protein concentration [mg/L] by urine creatinine concentration [mmol/L] and multiplying by 10. The protein: creatinine index in spot urine sample showed a reliable method of monitoring of progressive diabetic nephropathy as compared to 24 hours urine protein excretion rate. A significant correlation [r = 94] was found between the protein creatinine index and standard 24 hours urinary protein excretion in these patients [p< 0.001]. The index showed a significant negative correlation [r = 0.46] with glomerular filtration rate in progressive renal insufficiency in poorly controlled diabetics. The protein: creatinine index is quick and reliable method of estimation of proteinuria, to be used for monitoring of nephropathy leading to renal insufficiency in poorly controlled diabetics