Fecal microbiota transplantation in Parkinson's disease-A randomized repeat-dose, placebo-controlled clinical pilot study.

Background and purpose: The intestinal microbiome plays a primary role in the pathogenesis of neurodegenerative disorders and may provide an opportunity for disease modification. We performed a pilot clinical study looking at the safety of fecal microbiota transplantation (FMT), its effect on the microbiome, and improvement of symptoms in Parkinson's disease. Methods: This was a randomized, double-blind placebo-controlled pilot study, wherein orally administered lyophilized FMT product or matching placebo was given to 12 subjects with mild to moderate Parkinson's disease with constipation twice weekly for 12 weeks. Subjects were followed for safety and clinical improvement for 9 additional months (total study duration 12 months). Results: Fecal microbiota transplantation caused non-severe transient upper gastrointestinal symptoms. One subject receiving FMT was diagnosed with unrelated metastatic cancer and was removed from the trial. Beta diversity (taxa) of the microbiome, was similar comparing placebo and FMT groups at baseline, however, for subjects randomized to FMT, it increased significantly at 6 weeks (p = 0.008) and 13 weeks (p = 0.0008). After treatment with FMT, proportions of selective families within the phylum Firmicutes increased significantly, while proportion of microbiota belonging to Proteobacteria were significantly reduced. Objective motor findings showed only temporary improvement while subjective symptom improvements were reported compared to baseline in the group receiving FMT. Constipation, gut transient times (NS), and gut motility index (p = 0.0374) were improved in the FMT group. Conclusions: Subjects with Parkinson's disease tolerated multi-dose-FMT, and experienced increased diversity of the intestinal microbiome that was associated with reduction in constipation and improved gut transit and intestinal motility. Fecal microbiota transplantation administration improved subjective motor and non-motor symptoms. Clinical trial registration: ClinicalTrial.gov, identifier: NCT03671785.

Seasonal variation in trachoma prevalence among children, District Dera Ghazi Khan of Punjab, Pakistan.

OBJECTIVE: The study objective was to estimate trachoma prevalence in relation to seasonal variation among children. METHODS: Study Design was cross sectional and data was collected during all seasons of the year. After randomization of population units, 10% of them were identified by lottery and 5% of them were selected and examined for active trachoma case detection by simple random sampling technique. Total number of study participants were nine thousand seven hundred and ten (n=9710) from both urban and rural population units. The study was conducted during January -December 2018 during all three seasons of the year. After clinical examination, data was entered into a questionnaire Performa, which was used as tool for data collection. A Chi-square test was applied to compare trachoma cases among different seasons and among both boys and girls. RESULTS: Maximum burden of disease (62.4%) was reported during spring and winter season. Both spring and winter seasons have six months duration. During summer season, 70(37.6%) cases were reported. A highly significant (<0.01) relationship was reported between summer and spring seasons and trachoma prevalence (p < 0.01). A high prevalence was noted among female children. CONCLUSIONS: Higher prevalence of active trachoma was noted during summer season.

Approach to the patient with infectious colitis: clinical features, work-up and treatment.

PURPOSE OF REVIEW: To provide the definition, causes, and current recommendations for workup and treatment of acute infectious colitis in adults, a common medical problem of diverse cause. RECENT FINDINGS: The management of acute colitis in adults depend upon establishment of cause. Most forms of infectious colitis are treatable with antimicrobials. Multiplex polymerase chain reaction (PCR) followed by guided culture on PCR-positive pathogens can often confirm active infection while standard culture methods provide isolates for antibiotic susceptibility testing, subtyping, and Whole Genome Sequencing. SUMMARY: Patients with colitis may be suffering from a range of etiologies including infectious colitis, neutropenic colitis, drug-induced colitis, and inflammatory bowel disease. The present review was prepared to provide an approach to prompt diagnosis and management of acute colitis to prevent severe complications (e.g. dehydration and malnutrition, or toxic megacolon) and provide recommendations for antimicrobial therapy.

Safety and preliminary efficacy of orally administered lyophilized fecal microbiota product compared with frozen product given by enema for recurrent Clostridium difficile infection: A randomized clinical trial.

BACKGROUND: Fecal microbiota transplantation (FMT) via colonoscopy or enema has become a commonly used treatment of recurrent C. difficile infection (CDI). AIMS: To compare the safety and preliminary efficacy of orally administered lyophilized microbiota product compared with frozen product by enema. METHODS: In a single center, adults with ≥ 3 episodes of recurrent CDI were randomized to receive encapsulated lyophilized fecal microbiota from 100-200 g of donor feces (n = 31) or frozen FMT from 100 g of donor feces (n = 34) by enema. Safety during the three months post FMT was the primary study objective. Prevention of CDI recurrence during the 60 days after FMT was a secondary objective. Fecal microbiome changes were examined in first 39 subjects studied. RESULTS: Adverse experiences were commonly seen in equal frequency in both groups and did not appear to relate to the route of delivery of FMT. CDI recurrence was prevented in 26 of 31 (84%) subjects randomized to capsules and in 30 of 34 (88%) receiving FMT by enema (p = 0.76). Both products normalized fecal microbiota diversity while the lyophilized orally administered product was less effective in repleting Bacteroidia and Verrucomicrobia classes compared to frozen product via enema. CONCLUSIONS: The route of delivery, oral or rectal, did not influence adverse experiences in FMT. In preliminary evaluation, both routes appeared to show equivalent efficacy, although the dose may need to be higher for lyophilized product. Spore-forming bacteria appear to be the most important engrafting organisms in FMT by the oral route using lyophilized product. TRIAL REGISTRATION: ClinicalTrials.gov NCT02449174.

Homeostasis model assessment of insulin resistance in non-diabetic heart failure patients: A case-control investigation at tertiary care Hospitals of Karachi.

eart failure is a progressive, chronic disorder. Insulin resistance (IR) has been more and more involved as a preliminary metabolic perturbance predisposing to hyperglycemia, hyperlipidemia and atherosclerosis with others heart diseases. To investigate the relation of insulin resistance (IR) in non-diabetic heart failure patients this case-control study was carried out to ascertain the presence of IR with the aid of Homeostasis Model Assessment of Insulin Resistance (HOMA-IR) in non-diabetic heart failure patients (NDHF patients) compared with healthy controls. The sample size was calculated for both, cases (NDHF patients) and control (healthy subjects), which was initially consisted of 113 respondents each. The study consisted of two phase duration. In Phase I, NDHF patients were approached initially; only 80 patients with NDHF completed the study procedure. In Phase II, 80 healthy subjects were targeted and matched. Fasting blood glucose level (FBGL) and serum insulin was estimated. Mathematical model to quantify ß-cell function and insulin resistance was also computed through Homeostasis Model Assessment of Insulin Resistance (HOMA-IR) in both groups. Data was analyzed on SPSS version 16. Mean values with ± standard deviation (SD) of insulin (10.2±4.36) and HOMA-IR (2.52±1.15) were significantly (p<0.05) higher in NDHF patients as compared to control subject (6.4±3.39, 1.45±0.80). Average insulin to glucose ratio was 0.10±0.044 in NDHF patients which was significantly (p<0.0001) lowered in controls i.e., 0.073±0.039. Marginal and matrix plot analysis revealed that a higher patients count have had the HOMA-IR values <1.5 units while opposite scenario was observed in control group. Regression analyses of HOMA-IR with FBGL (as independent indicator) also authenticate the similar pattern. The present study concludes that insulin resistance (decreased insulin sensitivity) is a characteristic finding in Pakistani population of heart failure as compared to matched healthy controls.

Relationship of seminal free L-Carnitine with functional spermatozoal characteristics: Results from an observational study conducted in a tertiary care hospital of Karachi, Pakistan.

OBJECTIVE: To investigate the relationship of seminal free L-carnitine with functional spermatozoal characteristics. METHODS: This observational study was conducted at the Jinnah Postgraduate Medical Centre, Karachi, from August 2009 to June 2013, and comprised fertile and infertile subjects. Semen analysis was performed and reported for its volume, sperm count, motility and morphology according to the World Health Organisation's guidelines. Seminal free L-carnitine was estimated by high-performance liquid chromatography. Mean values of demographic characteristics, semen analysis and seminal free L-carnitine were compared, and possible relation of seminal free L-carnitine with functional spermatozoal characteristics was explored. RESULTS: Of the 61 participants, 19(31.1%) were fertile controls, while 42(68.9%) were infertile men. The mean age of controls was 32.7±1.44 years and that of infertile patients was 33.4±0.75 years (p=0.655). The mean seminal free L-carnitine was 447.6±23.86mmol/L among controls and 154.6±12.99 among patients (p=0.001). There was a strong positive correlation of seminal free L-carnitine with sperm count, total motility and normal morphology (p<0.01 each). CONCLUSIONS: The role of seminal free L-carnitine in the maintenance of normal functional spermatozoal characteristics was validated.

Inverse Correlation between Serum C-Reactive Protein and Magnesium Levels in Smokers and Nonsmokers.

BACKGROUND: Smoking plays a key role in increasing the inflammatory marker C-reactive protein (CRP). AIMS: To examine inverse correlation between CRP and magnesium levels in smokers and nonsmokers. MATERIALS AND METHODS: A total of 192 healthy adult male subjects were included in the present study, out of which 96 were smokers and the remaining 96 were nonsmokers having age range from 20 to 40 years, and all the subjects belonged to District Matyari of Hyderabad. Serum CRP was measured by NycoCard standard kit method and magnesium levels by DiaSys standard kit method in smokers and nonsmokers. RESULTS: The levels of serum CRP in smokers (14.62 ± 0.16 mg/L) is high as compared to nonsmokers (4.81 ± 0.38 mg/L), which is highly significant (P < 0.001). However, inverse results were seen for serum magnesium levels which were significantly higher (P < 0.001) in nonsmokers (2.52 ± 0.18 mg/L) as compared to the smokers (1.09 ± 0.38 mg/dL). A significant (P < 0.001) inverse relationship between serum CRP and magnesium concentrations were seen in smokers. CONCLUSION: This result shows that smoking increases serum CRP, an inflammatory marker parallel to decrease in serum magnesium levels in smokers having 20-40 years of age.

Prevalence of microalbuminuria with relation to glycemic control in type-2 diabetic patients in Karachi.

BACKGROUND: Diabetes is one of the most common endocrine disorders characterized by hyperglycaemia. Diabetic nephropathy is a consequence of long standing diabetes. The prevalence of microalbuminuria predicts progression to diabetic nephropathy. The present study was conducted to determine the prevalence of microalbuminuria in relation to duration of diabetes, BMI, Serum Creatinine and HbA1c in an ethnic group of Type 2 diabetes mellitus residing in Karachi. METHODS: This cross-sectional descriptive study was carried out in a community diabetic centre, located at Garden East Karachi from July to December 2007. One hundred known Type 2 diabetic patients with age 30-70 years were included in the study. Informed consent and a structured questionnaire of each patient were recorded. Fasting venous blood and morning urine sample was collected for analysis of creatinine, HbA1c and microalbuminuria respectively. Statistical analysis was done using SPSS version 13.0. Pearson correlation was applied to observe association of microalbuminuria with different parameters. All p-values < 0.05 were considered as statistically significant. RESULTS: Microalbuminuria had a highly significant correlation with duration of diabetes, serum creatinine (p < 0.001), HbA1c (p < 0.05) and BMI (p < 0.024). A strong correlation exists between age and serum creatinine (r = 0.73). CONCLUSION: The present study found an early onset of microalbuminuria in the selected community which could be due to poor glycaemic control (high HbA1c > 7%) or heredity factors. Screening for microalbuminuria and HbAlc test should be done in both newly and already diagnosed Type 2 diabetic patients as an early marker of renal dysfunction and glycaemic control.

Comparison of students' performance under composite scheme and split scheme of first professional MBBS examination.

BACKGROUND: Pakistan Medical and Dental Council has recently replaced 'composite scheme' of first Professional MBBS examination with 'split scheme'. In composite scheme First Professional MBBS examination is offered after 2 years in medical college while in split scheme the same examination is split into two parts, Part-I after first year and Part-II after completion of 2nd year in medical college. METHODS: This study analyzed the results of two batches of students successively passing the 1st professional MBBS examination at Nishtar Medical College, Multan under two different evaluation systems. One batch of students (N-49) passed under composite scheme in 2001 while the other batch (N-50) passed under the split scheme of 1st professional MBBS examination in 2002. RESULTS: Results showed a significant (P<0.05) increase in the pass percentage of students under the split scheme (74.65%) as compared with the composite scheme (64.03%). Students secured more total marks (615.36 +/- 35.99) under the split system as compared with the total marks obtained (587.22 +/- 33.85) under the composite system. More students (65.35%) obtained first division (60% or more marks) under the split scheme as compared with the composite scheme (36.29%). CONCLUSION: Students' performance seems to be better under the split scheme as compared with the composite scheme of 1st professional MBBS examination.