Role of oral hypoglycaemic drugs in preventing complication in non-alcoholic fatty liver disease with type 2 diabetes mellitus.

Objective: To determine the prevalence of non-alcoholic fatty liver disease, and the effect of oral hypoglycaemic drugs and lifestyle modifications in reducing fatty liver changes and liver enzymes in these patients. METHODS: The comparative, observational study was conducted at the Department of Pharmacology, Sohail University, Karachi, from October 2022 to October 2023, and comprised patients of either gender having elevated liver enzymes and ultrasound finding of fatty liver changes along with raised glycated haemoglobin, transaminases, total cholesterol and triglycerides. The participants were prescribed oral hypoglycaemic agents by endocrinologists. Those given empaglifazolin + metformin were in group A, empaglifazolin + linglaptin in group B, sitaglaptin + metformin in group C, metformin alone in group D and sitaglaptin alone in group E. Lifestyle modifications were advised in all the treatment groups, while control group F was only advised lifestyle modifications. The intervention lasted 3 months. Investigations included B-mode ultrasound liver, liver enzymes and glycated haemoglobin, which were done at baseline and after the intervention. Data was analysed using SPSS 25. RESULTS: Of 200 patients, 40 were males and 160 were females in ratio of 1:4. The overall mean age was 48±16 years. There were 154(77%) patients who had non-alcoholic fatty liver disease with type 2 diabetes mellitus, while 46(23%) had only fatty liver changes. There were 50(25%) patients in group A, 30(15%) in group B, 30(15%) in group C, 40(20%) in group D, 10(5%) in group E and 40(20%) in group F. Post-intervention improvement was noted in 48(24%) patients, with 20(41.7%) of them being in group A. Conclusion: The prevalence of non-alcoholic fatty liver disease with type 2 diabetes was high. Combination of empagliflozin + metformin along with lifestyle modifications was highly effective in reducing fatty changes and the level of liver enzymes.

--------Comparison of Hybrid-Simulation-Based Teaching with Traditional Teaching of Pharmacology.

OBJECTIVE: To compare the outcome of traditional teaching with hybrid simulation-based teaching for undergraduate medical students. Place and Duration of the Study: Department of Pharmacology, Jinnah Medical and Dental College, Karachi, Pakistan, from June to August 2023. STUDY DESIGN: Quasi-experimental study. METHODOLOGY: One hundred students from MBBS 3rd year were included in the study after taking the informed consent. Participants were divided into two cross-over groups and sampling was done randomly. Group A: (even roll numbers, n = 50) was the control group, taught by traditional lecture on positive inotropic medicines. Group B: (with odd roll numbers, n = 50) was the intervention group, taught the same topic by simulation-based teaching through 5 case scenarios. The teaching of this group was reinforced by role plays. Scores of post-test and retention test were compared by applying the Student's t-test. RESULTS: Students taught by traditional lectures i.e., Group A, their post-test mean scores were 30.7 ± 5.6, whereas Group B scored 45.7 ± 3.3, taught by hybrid stimulation (p <0.001). Retention test (MCQs based) was conducted after one month in which Group A obtained a mean score of 18.8 ± 9 with a passing percentage of approximately 30, whereas Group B obtained a score of 41.3 ± 5.6 (p <0.001). CONCLUSION: Hybrid-simulation-based teaching improved the immediate test scores as well as retention. KEY WORDS: Traditional teaching, Hybrid-simulation, MCQs, Retention test, Intervention group.

Comparison of Various Therapeutic Approaches to Manage Infertility in Polycystic Ovarian Syndrome.

OBJECTIVE: To compare the efficacies of common therapeutic regimens and their combinations, used in polycystic ovarian syndrome (PCOS) to improve fertility in reproductive-age women. STUDY DESIGN: A descriptive study. Place and Duration of the Study: Department of Obstetric Gynaecologist, Medicare Cardiac and General Hospital, Karachi, Pakistan, from November 2022 to July 2023. METHODOLOGY: Out of 300 patients with the symptoms of menstrual irregularities and infertility, 152 were diagnosed as PCOS patients based on the ultrasound and hormonal assays and selected for study purpose. They were divided according to their therapeutic regimen into four treatment groups, treated by different therapeutic agents. Group A received metformin 500 mg/day (n = 38); Group B received metformin + myo-inositol 1g (n = 49); Group C received metformin + letrozole 2.5 mg (n = 36), and Group D received metformin + letrozole + myo-inositol (n = 29), orally for three months. All continuous variables, such as body mass index (BMI), FSH, LH, FT4, and FSI were analysed by applying t-test to all therapeutic groups, keeping p ≤0.05 as the level of significance. RESULTS: HCG-positive was found as 86% (n = 33) in Group A, 63% (n = 31) in Group B, 52% (n = 19) in Group C, and 27% (n = 08) in Group D. There were statistically significant (p <0.001) changes in BMI, FSH, LH, FT4, and FSI as well. Metformin alone and metformin plus myo-inositol came out to be more effective than other regimens. CONCLUSION: Metformin alone and myo-inositol plus metformin are effective therapeutic options in PCOS-induced infertility problems. KEY WORDS: Polycystic ovarian syndrome, Infertility, Metformin, Myo-inositol, Letrozole, Menstrual irregularities.

Single step PCR for the identification of Low Density Lipoprotein Receptor (LDL-R) gene mutations.

BACKGROUND AND OBJECTIVE: This study was conducted to determine the common mutation of low density lipoprotein receptor in patients with familial hypercholesterolemia (FH) in our population and identify the different point mutation in the LDL-receptor gene. The main aim of this study was to reduce the cost of PCR without extracting DNA and do the diagnosis at single step. METHODS: This study was carried out in the period of one year, from 2009- 2011. All the patients selected for this study were from Dr. Ziauddin Hospital, National Institute of Cardiovascular Diseases, and Dr. Rubina Ghani's Pathological & Molecular Laboratories. While collecting the blood sample, the patients were in overnight fasting condition. The clinical and biochemical analysis was performed on hyperlipidemic patients (n=120) to determine the frequency of familial hypercholesterolemia in our population. After lipid profile the patients were selected and direct multiplex PCR (Polymerase chain reaction) was performed from whole blood collected in a single tube using forward and reverse primers of exons 3, 4, 9 and 14 of without extracting DNA. RESULTS: Genomic DNA was extracted from blood samples as well as direct whole ETDA blood of healthy control group and hypercholesterolemia patients to detect mutations in exons 3, 4, 9, and 14 of the LDLR gene, with modification in the technique by using type-specific primers. These results for exon 4 mutation were confirmed by DNA sequencing. CONCLUSION: Screening method based on PCR by using Kappa direct PCR could be a faster and cheaper method with least contamination for screening a large number of FH patients for mutation of LDLR gene.

Two novel mutations in exon 3 and 4 of low density lipoprotein (LDL) receptor gene in patients with heterozygous familial hypercholesterolemia.

OBJECTIVE: To determine the common mutation of low density lipoprotein receptor in hypercholesterolemia patients requiring screening for heterozygous familial hypercholesterolemia (HeFH) in Karachi. STUDY DESIGN: Case-series. PLACE AND DURATION OF STUDY: Dr. Ziauddin Hospital Laboratory and Dr. Rubina Ghani's Pathological and Molecular Laboratories, Karachi, for the PCR bench work from June 2008 to October 2009. METHODOLOGY: All the patients selected for this study were from Dr. Ziauddin Hospital and National Institute of Cardiovascular Diseases. All the patients having high total cholesterol and LDL-cholesterol were included in this study with premature coronary artery diseases or a family history of hypercholesterolemia. Exclusion criteria included Diabetes mellitus, hypertension, renal disease, hypothyroidism and steroid therapy. After lipid profile with overnight fasting, DNA was extracted from whole blood collected in EDTA (ethylenediamine tetra acetic acid) tube and multiplex PCR (polymerase chain reaction) using forward and reverse primers of exons 3, 4, 9 and 14 of base pairs 162, 431, 550 and 496 respectively. RESULTS: Out of total of 120 hypercholesterolemia cases, 42 patients were classical cases of HeFH (heterozygous familial hypercholesterolemia) with xanthomas, xanthelasmas and LDL-C > 160 mg/dl. The total cholesterol (260± 57 mg/dL) and LDL-C (192 ± 39 mg/dL ) of cases was significantly high as compared to, controls having total cholesterol (184 ± 27 mg/dL) and LDL-C (105 ± 22 mg/dL), p > 0.001. Two novel point mutations were noted in exon 3 and exon 4. The other 78 cases were probable with raised LDL-C (low density lipoprotein cholesterol) and family history of premature coronary heart diseases. CONCLUSION: The frequency of HeFH was 35% classical and 65% probable cases out of total 120 hypercholesterolemia patients from two tertiary care hospitals in Karachi. The point mutation on exon 3 and exon 4 of LDLR gene was the most common. PCR is useful for the detection of large re-arrangements in the LDL-receptor gene and is a rapid and reliable method for diagnosis of familial hypercholesterolemia.

Carotid intima-media thickness correlation with lipid profile in patients with familial hypercholesterolemia versus controls.

OBJECTIVE: To determine the variations in carotid intima-media thickness (CIMT) in familial hypercholesterolemia (FH) patients and its use as predictive marker for premature cardiovascular diseases. STUDY DESIGN: Comparative study. PLACE AND DURATION OF STUDY: National Institute of Cardiovascular Diseases and Dr. Ziauddin Hospital, Karachi, from June 2008 to October 2009. METHODOLOGY: Familial hypercholesterolemia was clinically diagnosed by premature coronary diseases, xanthomas, arcus cornealis and family history of premature coronary heart diseases. Controls were age matched normal individuals without hypercholesterolemia. Their lipid profile was tested after overnight fasting. CIMT was measured in mm using B-mode ultrasonography using linear probe. Student t-test was applied to compare mean CIMT of cases and the control. The mean CIMT values of the FH cases were correlated with LDL using Pearson's correlation test. RESULTS: Forty cases with hypercholesterolemia gave consent to participate in the study. These patients had total cholesterol ≥200 mg/dL and LDL ≥160 mg/dL as compared to twenty controls of similar age with total cholesterol ≤200 mg/dL and LDL ≤130 mg/dL. Mean CIMT for the cases was 0.77 ± 0.18 mm while mean CIMT for control was 0.59 ± 0.08 mm. The mean CIMT for the cases ranged from 0.7-1.83 mm and 0.48-0.73 mm for controls. Among the FH cases, 25% (n=11) had arterial plaques. Mean CIMT was significantly correlated to LDL-cholesterol (r = 0.725**, p < 0.001). CONCLUSION: In this study, CIMT was found to be significantly increased in familial hypercholesterolemia and it correlated with raised LDL-cholesterol. Both are predictive of premature cardiovascular diseases.