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Biomedical subjects

S Hamid

Publications and source records attributed to S Hamid.

At least 19 recordsLinked to original sources

Correlation between translation efficiency and outcome of combination therapy in chronic hepatitis C genotype 3.

Combination therapy with interferon-alpha (IFN-alpha) and ribavirin (RBV) in chronic hepatitis C demonstrates the best responses against hepatitis C virus (HCV) of genotype 3. Still, it has proven to be ineffective in 20-30% of patients infected with this genotype. In the present study, we analysed the translation efficiency mediated by the internal ribosome entry site (IRES) region in HCV genotype 3 genomes isolated from sustained responders (SR) and non-responders (NR), assuming that this may influence the outcome of treatment. Pretreatment isolates of genotype 3 from 22 individuals (15 SR, seven NR) were selected for such analyses. The IRES region [nucleotide (nt) 1-407] was cloned into a dual luciferase vector and IRES activity assessed following transfection into various cell lines. Low relative translation efficiency was observed for IRES elements derived from SR patients, whereas those of NR patients showed significantly greater translation efficiency (29.7 +/- 13 vs 69.4 +/- 22; P < 0.01). Subsequently, the effect of IFN-alpha plus RBV on IRES-driven translation in vitro was determined. A greater suppressive effect was observed on IRES activity isolated from seven SR patients, when compared with seven NR patients. In conclusion, IRES efficiency in vitro correlated with treatment response for HCV genotype 3. Further studies are warranted to investigate whether IRES efficiency in vitro, or sequence motifs associated with IRES efficiency, will be worthwhile to explore as prognostic tools for other HCV genotypes in the treatment of chronic HCV infection.

Adult↗

Pill-induced esophageal injury: endoscopic features and clinical outcomes.

BACKGROUND AND STUDY AIMS: Pill-induced esophageal injury is a common but under-reported problem. The purpose of this study was to explore the clinical and endoscopic features, and the outcome of pill-related esophageal injury. PATIENTS AND METHODS: Endoscopy records for the period from January 1997 to June 2003 were searched for reports of esophageal pathology. The records of patients with pill-induced esophageal injury were evaluated. RESULTS: A total of 92 patients with pill-induced esophageal injury were identified (33 men, 59 women; mean age 59, range 25-87). Common symptoms were odynophagia (n = 69, 75 %), chest pain (n = 55, 60 %), vomiting (n = 53, 58 %), dysphagia (n = 31, 33 %), and hematemesis (n = 14, 15 %). The endoscopic findings in the esophagus were: erythema in 76 patients (83 %), erosions in 53 patients (58 %), ulcers in 24 patients (26 %), seven of which were "kissing" ulcers, esophageal ulcer with bleeding in 17 patients (18 %), and esophageal strictures in seven patients (8 %). The causative pills were nonsteroidal anti-inflammatory drugs in 38 patients (41 %), tetracyclines in 20 patients (22 %), potassium chloride tablets in nine patients (10 %), alendronate in eight patients (9 %), and other drugs in 17 patients (18 %). Underlying diseases included diabetes in 60 patients (65 %), ischemic heart disease in 39 patients (42 %), and hypothyroidism in four patients (4 %). The mean hospital stay was 1.94 days; 14 patients (15 %) required injection of epinephrine 1 : 10,000 to control bleeding; and two patients died. CONCLUSIONS: Pill-induced injury may present as erosions, kissing ulcers, and multiple small areas of ulceration with bleeding, mainly in the middle third of the esophagus. Advanced age, female gender, diabetes, and ischemic heart disease were common associations. The majority of patients made an uneventful recovery.

Aged↗

Outcomes, cost and long term survival of patients referred to a regional weaning centre.

BACKGROUND: Regional weaning centres provide cost effective care for patients who have undergone prolonged mechanical ventilation. There are few published European data on outcomes in these patients. METHODS: Patients admitted for weaning to the Lane Fox Respiratory Unit (LFU) between January 1997 and December 2000 were identified. The proportion weaned from mechanical ventilation, in-hospital mortality, and subsequent survival after discharge were examined. RESULTS: A total of 153 patients had been ventilated for a median of 26 days before transfer. The daily cost per patient stay was 1350. Fifty eight patients (38%) were fully weaned, 42 (27%) died, and 53 (35%) required ventilatory support at discharge from hospital of whom 36 (24%) required only nocturnal ventilation. Univariate analysis showed increasing age (OR 1.06, p<0.001), length of ICU stay (OR 1.02, p = 0.001), APACHE II predicted risk of death score (OR 1.02, p = 0.05), and a surgical cause for admission (OR 4.04) were associated with mortality. Neuromuscular/chest wall conditions were associated with low mortality (OR 0.36) but low likelihood of weaning from ventilation (OR 0.28). Female sex (OR 2.13, p = 0.03) and COPD (OR 2.81) were associated with successful weaning. Overall survival at 3 years from admission was 47%. Long term survival was lowest in patients with COPD. CONCLUSIONS: Most patients survived to leave hospital, the majority having been liberated from ventilatory support. Survivors were younger and spent less time ventilated in the referring ICU. The underlying diagnosis determined success of weaning, hospital survival, and long term outcome.

APACHE↗

Epstein-barr virus detection in tumors of upper gastrointestinal tract. An in situ hybridization study in Pakistan.

To examine the potential role of Epstein-Barr virus (EBV) in the carcinogenesis of upper gastrointestinal tract, we conducted an in situ hybridization assay for EBV-encoded small RNA (EBER) expression in the tumors of 56 oral and 50 esophageal squamous cell carcinoma (SCC) cases, and 52 stomach adenocarcinoma cases diagnosed in the King Edward Medical College and Allama Iqbal Medical College Lahore, Pakistan between 1996-2002. There were no malignancies with positive EBER expression in oral and esophageal SCC. Only one out of the 52 gastric adenocarcinoma cases (1.9%) was positive for EBER expression, and this frequency was relatively low as compared to cases reported worldwide. The case was a 42 year-old male patient and histologically classified as moderately differentiated tubular adenocarcinoma. In conclusion, the frequency of EBV-associated gastric carcinoma was relatively low in Pakistan. The present study could not confirm the involvement of EBV in the carcinogenesis of oral and esophageal SCC.

Adenocarcinoma↗

Incidence of traumatic injection neuropathy among children in Pakistan.

We used acute flaccid paralysis surveillance data collected between 1 January 2001 and 31 December 2003 from the Pakistan Polio Eradication Initiative to describe the epidemiological characteristics and disease burden of traumatic injection neuropathy among children aged under 15 years. Of the 5627 acute flaccid paralysis cases reported, 456 were identified as traumatic injection neuropathy by case review. The condition was more common in younger children who were also more likely to have persistent paralysis. We estimate that the annual incidence of traumatic injection neuropathy rate in Pakistan is 7.1 per 1 000 000 in children under 3 years old.

Acute Disease↗

Injections in health care settings: a risk factor for acute hepatitis B virus infection in Karachi, Pakistan.

A case control study was conducted to identify the association of therapeutic injections with acute hepatitis B virus (HBV) infection in Karachi, Pakistan. We enrolled 67 cases of acute HBV infection (IgM anti-HBc positive) and 247 controls (anti-HBc negative) from four hospitals of Karachi during July 2000-June 2001. Exposure to various risk factors during the period relevant to the incubation period of HBV was recorded both from cases and controls using a structured questionnaire. Multivariate logistic regression analysis of the data showed that cases were more likely to have received one injection (OR = 4.0; 95 % CI 1.4, 11.1), or more than one injection (OR = 6.3; 95 % CI 3.2, 12.4) compared to controls. The estimated population attributable risk (PAR) for therapeutic injections was 53%. Also the cases compared to controls were more likely to have household size of seven or more (OR = 1.9; 95 % CI 0.95, 3.9). This study showed that unsafe therapeutic injections appear to be the major risk factor for acute HBV infection and needs immediate focus from public health stand point.

Acute Disease↗

Improved detection of hepatocyte proliferation using antibody to the pre-replication complex: an association with hepatic fibrosis and viral replication in chronic hepatitis C virus infection.

To test the hypothesis that hepatitis C virus (HCV) might induce hepatocyte proliferation directly, thereby predisposing HCV carriers to cirrhosis and hepatocellular carcinoma, we have used a new method to identify proliferating hepatocytes, employing a novel monoclonal antibody to minichromosome maintenance (Mcm) proteins, essential components of the pre-replication complex. Antibody to Ki-67, a conventional marker of cell division, was also studied. Eighty-seven patients with chronic HCV infection and a broad spectrum of histological change were studied. Proliferation was observed rarely in hepatocytes from normal liver from healthy controls (always less than 0.01%). However, proliferating hepatocytes were detected in all HCV-infected patients and the proportion of hepatocytes expressing Mcm-2 (3-40%) always exceeded that expressing Ki-67 (1-14%) and correlated positively with increasing stage of fibrosis (P = 0.0001) and viral replication (P = 0.0004). There were weaker but significant associations between the proportion of hepatocytes expressing Mcm-2 and inflammatory indices including interface hepatitis, portal tract inflammation, lobular inflammation and steatosis. There was no association between the proportion of hepatocytes expressing Mcm-2 and age, gender or past alcohol consumption, but there was a weak association with current consumption of alcohol (P = 0.0067). The proportion of Ki-67 hepatocytes did not correlate with any clinical, laboratory or histological parameter. Mcm-2 was also detected in bile duct cells, sinusoidal lining cells and infiltrating lymphocytes, but at low frequency. These data indicate first, that Mcm-2 is a more sensitive marker of hepatocyte proliferation than Ki-67, second that many hepatocytes in chronic HCV infection have entered the cell cycle and third, suggest that interference with the hepatocyte cell cycle might be an alternative approach to therapy.

Adult↗

Irritable bowel syndrome in health care professionals in Pakistan.

OBJECTIVE: To evaluate the symptomatology of irritable bowel syndrome (IBS) among health care professionals attending an IBS symposium in a tertiary care university hospital. METHOD: A questionnaire designed to incorporate Manning and Rome II criteria was distributed among participants of an IBS symposium, most of them were health care professionals. A total of 100 questionnaires were distributed, 41 had symptoms fulfilling criteria of IBS. In these patients male: female ratio was 28:13 with age range 18-68. RESULTS: The predominant symptom was abdominal pain 87.8 % (36/41) which was aggravated post-prandially 72.2% (29/41), relieved following defecation in 87% (35/41) with a sense of incomplete evacuation 85.3% (35/41) and distention after defecation in 80.4% (33/41). Anxiety and depression was present in 80% (33/41) as an extraintestinal symptom. CONCLUSION: Irritable bowel syndrome is common in health care workers with intestinal and extraintestinal manifestations being equally common.

Adolescent↗

Sequence diversity of TT virus in geographically dispersed human populations.

TT virus (TTV) is a newly discovered DNA virus originally classified as a member of the Parvoviridae. TTV is transmitted by blood transfusion where it has been reported to be associated with mild post-transfusion hepatitis. TTV can cause persistent infection, and is widely distributed geographically; we recently reported extremely high prevalences of viraemia in individuals living in tropical countries (e.g. 74% in Papua New Guinea, 83% in Gambia; Prescott & Simmonds, New England Journal of Medicine 339, 776, 1998). In the current study we have compared nucleotide sequences from the N22 region of TTV (222 bases) detected in eight widely dispersed human populations. Some variants of TTV, previously classified as genotypes 1a, 1b and 2, were widely distributed throughout the world, while others, such as a novel subtype of type 1 in Papua New Guinea, were confined to a single geographical area. Five of the 122 sequences obtained in this study (from Gambia, Nigeria, Papua New Guinea, Brazil and Ecuador) could not be classified as types 1, 2 or 3, with the variant from Brazil displaying only 46-50% nucleotide (32-35% amino acid) sequence similarity to other variants. This study provides an indication of the extreme sequence diversity of TTV, a characteristic which is untypical of parvoviruses.

Africa, Western↗

Meta-analysis of the safety and tolerability of two dose regimens of buspirone in patients with persistent anxiety.

Buspirone is an azapirone with 5-HT1A partial agonist activity which has demonstrated efficacy in the treatment of generalized anxiety disorder, commonly referred to as persistent anxiety. In this meta-analysis report, safety results from two studies comparing buspirone 15 mg twice daily (BID) with buspirone 10 mg three times daily (TID) in patients with persistent anxiety are presented. In the study protocols, qualified patients completed a 7-day placebo lead-in phase and were randomized to receive buspirone 30 mg per day, as either a BID or TID regimen, for 6-8 weeks. A total of 289 patients received buspirone 15 mg BID (n = 144) or 10 mg TID (n = 145) at 15 sites. The incidence of adverse events was similar between the two treatment groups, except for a significantly greater incidence of palpitations in patients receiving buspirone BID (5%) compared to buspirone TID (1%). The most frequently reported adverse events for both buspirone BID- and TID-treated patients were dizziness, headache, and nausea. No appreciable differences between treatments were observed for vital signs, physical exam, ECG, or clinical laboratory results. A change to BID dosing for buspirone may offer convenience and possibly higher compliance in patients with persistent anxiety without compromising the excellent safety and tolerability profile of the medication.

Anti-Anxiety Agents↗

Evaluation of an electronic hand-held spirometer in patients with asthma.

In this pilot study we assessed patient compliance and acceptability of data recorded in the home environment by asthmatics using a Vitalograph 2110 spirometer which measures peak expiratory flow rate (PEFR) and forced expiratory volume in 1 s (FEV1). This meter automatically time and date stamps all measurements and can also assess the technical acceptability of results. Data are uploaded to a personal computer for review and analysis. We recruited 30 patients (10 male and 20 female, age range 21-72 years) from the chest clinic at Guy's Hospital (n = 20) and from a GP clinic (n = 10). Patients were asked to record spirometry data using the meter at set times (8.00 a.m. and 8.00 p.m.) for 2 weeks. The spirometer incorporated an alarm to remind patients to take measurements. All patients completed the study. Mean (SD) compliance with spirometer use was 100.8% (49.9%). Nineteen patients had a compliance rate of between 80% and 120% of expected use. Timing of recordings was compared with the scheduled times of 8.00 a.m. and 8.00 p.m. Values recorded with +/- 2 h were judged as acceptable. For morning recordings 67.4% of all values and for evening recordings 71.7% of all values met this criterion. Technical acceptability of spirometry data was also assessed by using quality assurance criteria recorded by the spirometer. Valid tests were performed for 75.2% of all recordings. Twenty-two patients performed valid tests for 80-100% of the time. We suggest that the use of an electronic meter in the home environment is practical and is likely to generate more accurate and reliable data.

Adult↗

Single centre open study to compare patient recording of PRN salbutamol use on a daily diary card with actual use as recorded by the MDI compliance monitor.

The aim of this study was to assess the patients' use of inhaled short acting bronchodilators as rescue therapy during a 4-week study period. In this study an electronic metered-dose inhaler compliance monitor (MDI-CM) was used to measure the time and date of actuations of the device and this information was then compared with the patients' self reporting diary card (DC). Salbutamol canisters were used in the compliance monitor. The study was approved by the local ethics committee, and written informed consent was obtained from all patients. Patients aged 18 years and over who were either receiving, or in the investigators opinion required, inhaled salbutamol on a PRN basis were enrolled for a 4-week monitoring phase during which all rescue salbutamol used was obtained from the MDI-CM. Patients were recording their use of salbutamol in the DC each morning and evening. There was a 2-week follow-up period following completion of the monitoring phase or withdrawal from the study. Forty-four patients were enrolled and 35 patients completed the study. The mean age (range) was 43 (20-76) years and mean FEV1 2.32 (0.7-4.0) 1, with male:female ratio of 19:25. Comparison of MDI-CM and DC recordings showed patients fell into three categories: (1) patients who used rescue salbutamol appropriately and whose MDI-CM and DC recordings matched closely; (2) patients who used rescue salbutamol for acute relief but whose MDI-CM and DC recordings did not correlate and (3) patients whose use of rescue salbutamol was inappropriate or erratic according to the MDI-CM but whose DC indicated good compliance. This category of patients include those who 'dumped' all their salbutamol before attending clinic appointments. There was no significant difference in the demographic details or the severity of disease in the three groups. Recorded use of 'rescue' bronchodilator is frequently used as an indicator of efficacy for new anti-asthma therapies. This study comparing electronic data monitoring and remembered rescue salbutamol highlights the potential errors that can occur without accurate recording systems.

Adrenergic beta-Agonists↗