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Biomedical subjects

I Malik

Publications and source records attributed to I Malik.

At least 19 recordsLinked to original sources
PubMed2006

Potentiation of in vivo neuroprotection by BclX(L) and GDNF co-expression depends on post-lesion time in deafferentiated CNS neurons.

To elucidate effective and long-lasting neuroprotective strategies, we analysed a combination of mitochondrial protection and neurotrophic support in two well-defined animal models of neurodegeneration, traumatic lesion of optic nerve and complete 6-hydroxydopamine (6-OHDA) lesion of nigrostriatal pathway. Neuroprotection by BclX(L), Glial cell line-derived neurotrophic factor (GDNF) or BclX(L) plus GDNF co-expression were studied at 2 weeks and at 6-8 weeks after lesions. In both lesion paradigms, the efficacy of this combination approach significantly differed depending on post-lesion time. We show that BclX(L) expression is more important for neuronal survival in the early phase after lesions, whereas GDNF-mediated neuroprotection becomes more prominent in the advanced state of neurodegeneration. BclX(L) expression was not sufficient to finally inhibit degeneration of deafferentiated central nervous system neurons. Long-lasting GDNF-mediated neuroprotection depended on BclX(L) co-expression in the traumatic lesion paradigm, but was independent of BclX(L) in the 6-OHDA lesion model. The results demonstrate that neuroprotection studies in animal models of neurodegenerative diseases should generally be performed over extended periods of time in order to reveal the actual potency of a therapeutic approach.

Animals↗
PubMed2004

Treatment options for von Hippel-Lindau's haemangioblastomatosis: the role of gamma knife stereotactic radiosurgery.

Haemangioblastomas secondary to von Hippel-Lindau (VHL) disease can be difficult to manage surgically, which has lead to an interest in the use of stereotactic radiosurgery. Retrospectively reviewed here are 30 tumours treated in 14 patients with a mean +/- SD follow-up of 34 +/- 24 months. During this time, three of the 14 patients (21%) died, two of generalized progressive disease. Before radiosurgery, the median time between interventions for cranial haemangioblastomas was 3 years (mean 3.9 +/- 5.0 years). After radiosurgery, the tendency for cranial disease progression was similar, 50% of patients developing further disease by 5 years. Local tumour control was achieved in the majority of cases and estimates of this are included. Radiosurgery is a useful palliative measure controlling the majority of haemangioblastomas, although its efficacy in these patients is limited by the tendency of further disease to develop or progress intracranially.

Adult↗
PubMed2003

Haemodynamic and electrocardiographic consequences of severe nicorandil toxicity.

A 35 year old woman was admitted to the emergency department two hours after ingesting 60x20 mg tablets of nicorandil, total 1.2 g. The dominant feature of icorandil toxicity was profound peripheral vasodilatation associated with coronary hypoperfusion. Despite widespread electrocardiographic signs of myocardial ischaemia, there was no evidence of myocardial damage and no serious cardiac arrhythmia. Volume loading and pressor support proved to be an effective treatment strategy.

Adult↗
PubMed2002

Comparison of meropenem with ceftazidime as monotherapy of cancer patients with chemotherapy induced febrile neutropenia.

BACKGROUND: Ceftazidime is commonly used as monotherapy of cancer patients with fever and neutropenia. Concern, however, has been raised regarding potential for drug resistance due to its widespread use. Meropenem is a new carbapenem with more extended antibacterial spectrum including anaerobes. It provides better coverage against gram positives. Hence, it may offer an advantage over ceftazidime. PATIENTS AND METHODS: We prospectively treated 49 patients hospitalized for fever (> 38 degrees C) and neutropenia (ANC < or = 500/cmm) with meropenem. We compared their outcome with 50 patients who consecutively received ceftazidime in the immediate past for the same indication. RESULTS: Comparison of demographic features between the 2 groups revealed no differences in age, gender, type of neoplasm, number of patients with prior antibiotic use, number of days since chemotherapy, absolute neutrophil count and number of patients previously or already hospitalized. Duration of fever, duration of neutropenia and number of patients with pyrexia of undetermined origin were also similar. Therapeutic outcome was same between the two groups. Eighty four percent of patients receiving meropenem and 79% receiving ceftazidime required no modification of the initially assigned therapeutic regimen. Two patients receiving meropenem died. Toxicity was minimal. CONCLUSION: We conclude that meropenem offers no significant advantage over ceftazidime in the management of neutropenic febrile patients.

Adult↗
PubMed2001

Soluble adhesion molecules and prediction of coronary heart disease: a prospective study and meta-analysis.

BACKGROUND: Previous studies have suggested that circulating concentrations of soluble adhesion molecules are useful predictors of risk of coronary heart disease (CHD). Larger studies are needed, however, to test this hypothesis. METHODS: We measured serum concentrations of four soluble cell adhesion molecules (intercellular adhesion molecule-1 [ICAM-1], vascular cell adhesion molecule-1 [VCAM-1], E-selectin, and P-selectin) in the stored baseline serum samples of 643 men with coronary heart disease and 1278 controls nested in a prospective sutdy of 5661 men who were monitored for 16 years. We also did a meta-analysis of previous relevant studies to place our findings in context. RESULTS: Concentrations of soluble adhesion molecules were significantly associated with one another, with other markers of inflammation, and with some classic coronary risk factors. For ICAM-1, the odds ratio for CHD was 1.68 (95% CI 1.32-2.14) in a comparison of men in the top third with those in the bottom third of baseline measurements after adjustments for age and town. This decreased to 1.11 (0.75-1.64) after adjustment for some classic coronary risk factors and indicators of socioeconomic status. For the three other cell adhesion molecules, the odds ratios for CHD, first adjusted for age and town only, and then additionally adjusted for other risk factors, were: VCAM-1: 1.26 (0.99-1.61) and 0.96 (0.66-1.40); E-selectin: 1.27 (1.00-1.61) and 1.13 (0.78-1.62); and P-selectin: 1.23 (0.96-1.56) and 1.20 (0.81-1.76). INTERPRETATION: The measurement of these adhesion molecules is unlikely to add much predictive information to that provided by more established risk factors.

Adult↗
PubMed2001

Multispectral imaging of tablets in blister packaging.

This experiment tested the hypothesis that using near-infrared (IR) imaging spectrometry on tablets through blister packs permits the identification and composition of multiple individual tablets to be determined simultaneously. Aspirin was selected for this study because its breakdown mechanism is well understood. Near-IR cameras were used to collect thousands of spectra simultaneously from a field of packaged aspirin tablets. Tablets were selected by a principal component analysis selection algorithm. Graphs of the columns of the transformation matrix showed that salicylic acid and acetylsalicylic acid in the samples were modeled by the principal components. The bootstrap error-adjusted single-sample technique chemometric-imaging algorithm was used to draw probability-density contour plots that revealed tablet composition. Choice of color was used to represent constituent identity, whereas intensity represented concentration. The percentage of usable pixels in the indium antimonide (InSb) array was 99.9%. The SEP was 0.06% of the tablet mass for both water uptake and salicylic acid production. The number of tablets that a typical near-IR camera can currently analyze simultaneously was also estimated to be approximately 1300.

Aspirin↗
PubMed2001

Clinical characteristics and therapeutic outcome of patients with febrile neutropenia who present in shock: need for better strategies.

OBJECTIVE: To study the frequency of neutropenic febrile patients who present in shock, to evaluate the influence of this presenting feature on response to antibiotic therapy, morbidity, and mortality and to identify discriminating demographic features and clinical characteristics of these individuals. METHODS: Prospectively collected data on all episodes of fever and neutropenia observed in cancer patients who were hospitalized for parenteral antibiotic therapy. RESULTS: Five hundred and seventy-six patients were evaluated; 22 (3.8%) presented in shock. This group of individuals was compared with the remainder. Patients presenting in shock were more likely to be older (P< 0.01) and have progressive unresponsive cancer (P< 0.01). They were also more likely to present with septic appearance (P< 0.01), dehydration (P< 0.01), diarrhoea (P< 0.01), altered mental status (P< 0.01) clinical bleeding (P= 0.02) and dyspnoea (P< 0.01). They more often had anaemia (P< 0.01), thrombocytopenia (P= 0.02) and abnormal liver function tests (P< 0.01). Eight of the 22 patients presenting in shock had documented bacteraemia. Non-bacteraemic microbiological infections were observed in three patients. Five patients had clinical evidence of infection and another five were severely dehydrated and volume depleted. One patient had cardiogenic shock. Three patients were managed with monotherapy, 19 received combination antibiotics as initial empirical therapy. Overall outcome of these patients was extremely poor, particularly those with infectious aetiology. Eighteen (82%) patients expired. CONCLUSION: Neutropenic febrile patients who present in shock have extremely poor outcomes irrespective of type of initial antibiotic therapy. Intense efforts are required to improve their outcome.

Adolescent↗
PubMed1999

Prospective randomized comparison of tropisetron with and without dexamethasone against high-dose metoclopramide in prophylaxis of acute and delayed cisplatin-induced nausea and vomiting.

Several studies have confirmed the efficacy of high-dose metoclopramide and, more recently, serotonin antagonists, with and without dexamethasone, in the prophylaxis of cisplatin-induced nausea and vomiting. Most of these trials have been reported from Western countries. There is little or no information about the efficacy and tolerability of these agents in ethnic groups in other countries. Furthermore, many patients in the developing countries cannot afford serotonin antagonists. The result is a critical need to evaluate these agents and justify their increasingly common use. The authors performed a prospective randomized trial to compare the efficacy and tolerability of tropisetron with and without dexamethasone against high-dose metoclopramide cocktail in patients receiving a uniform dose of cisplatin (100 mg/m2). Metoclopramide 2 mg/kg was combined with clemastine, dexamethasone, and lorazepam. These drugs were initially repeated at short intervals and subsequently given in the oral form for the next 5 days. Tropisetron 5 mg was administered intravenously 15 minutes immediately before cisplatin therapy and followed up with oral therapy for 5 days. The third group received the same doses of tropisetron along with dexamethasone before cisplatin and twice daily thereafter. The authors randomized 301 episodes. The patient characteristics were well balanced between the three groups. Acute nausea and vomiting were completely prevented in almost two thirds of patients receiving metoclopramide and tropisetron plus dexamethasone. These results are significantly superior to those of tropisetron alone (p < 0.01). Similarly, delayed nausea and vomiting were significantly better controlled with metoclopramdie cocktail and tropisetron plus dexamethasone than with tropisetron alone. Side effects were generally mild; however, they were more frequent with metoclopramide. The authors conclude that metoclopramide-based combination antiemetic therapy continues to be a cheaper alternative to serotonin antagonists and equally effective. Metoclopramide-based therapy, however, is more labor intensive, and issues related to administrative errors, side effects, and compliance gain increasing importance. The identification of persons at a higher risk for metoclopramide-induced side effects may help minimize the unacceptable consequences of therapy.

Acute Disease↗
PubMed1999

Clinicopathological features and management of Pakistani patients with multiple myeloma.

OBJECTIVE: Purpose of the study was to evaluate the clinicopathological features of multiple myeloma in Pakistan and to study the influence of therapeutic management in these cases. METHODS: We retrospectively analyzed 99 newly diagnosed patients with multiple myeloma seen from 1988 to 1996. Diagnostic criteria included bone marrow plasmacytosis, monoclonal gammopathy in serum or urine and radiological evidence of skeletal lesions. RESULTS: There were 57 males and 42 females. Mean age of the patients was 58 years with a range of 23 to 86 years. One-third of the patients were bed ridden at the time of presentation. Common presenting symptoms included bone pain (82%), fatigue (78%) and backache (73%). Physical findings, laboratory features and radiologic assessment revealed pallor (56%), severe anaemia with hemoglobin < 8.5 gm/dl (39%), creatinine > or = 2 2 mg/dl (57%), serum calcium > or = 12 gm/dl (23%), uric acid > or = 8 gm/dl (47%) and albumin < or = 3.5 gm/dl (63%). Commonest monoclonal gammopathy was igG kappa. Majority (71%) of the patients presented with stage III disease. Commonest chemotherapeutic regimen utilized was melphalan and prednisolone which was administered to 88% of the patients. Complete remission was observed in 25% and partial remission in 36% of the evaluated patients. Commonest complication during the course of disease was related to skeletal involvement followed by renal failure and bone marrow suppression. Median survival of the patients was 34 months. CONCLUSION: Multiple myeloma patients in Pakistan are younger, more frequently have poor performance status and more often present with advanced stage of disease. Response to therapy, however, is adequate and survival is comparable to Western patients.

Adult↗
PubMed1998

On the quantification of suckling intensity in primates.

The inhibitory effect that suckling has on the reproductive function of primate mothers varies as a function of the intensity with which they are suckled. Here we present an easily computed index of one parameter of suckling intensity, namely the temporal patterning of suckling bouts. High intensity suckling is characterized by frequent nursing bouts demarcated by short interbout intervals. Therefore, our suckling index is based on the brevity of observed interbout intervals, more specifically the proportion of such intervals that fail to exceed a criterion length. The index is an appropriate means of making interspecific comparisons of the development of infant suckling and is well suited for application to field data that include interbout intervals that were not observed in their entirety. To demonstrate its utility, we apply the index to field data collected on the suckling behavior of free-ranging rhesus monkey (Macaca mulatta) infants in India. In this context, we demonstrate that, in rhesus, between-infant differences in suckling intensity manifest themselves early in the postpartum period and contribute to between-female differences in the timing of first mating postpartum.

Animals↗
PubMed1998

Role of fibreoptic bronchoscopy in the management of immunocompromised patients with pulmonary infiltrates.

Immunocompromised patients are prone to develop various pulmonary complications. The range of diagnostic possibilities is wide, infection being the commonest cause. Non-invasive diagnostic tests are often unrewarding. In this study, we have evaluated the diagnostic efficacy and safety of fibreoptic bronchoscopy in immunocompromised patients with pulmonary infiltrates. Patients tolerated the procedure well. This technique identified the etiology in up tp 75% of cases. After treatment based on the result of bronchoscopy, 63% patients improved and were discharged.

Adult↗
PubMed1997

Hepatitis C virus (HCV) genotypes and chronic liver disease in Pakistan.

UNLABELLED: Hepatitis C virus (HCV) is classified into different types depending on nucleotide sequence variability. Detailed information on the distribution of various HCV genotypes in some geographical areas is available but little is known about Pakistan. In this study, a 5' non-coding region (NCR)-based restriction fragment length polymorphism (RFLP) genotyping assay was used to investigate the genotype distribution in a large series of HCV-infected patients in Karachi, Pakistan. Serum samples from 74 hepatitis B surface antigen (HBsAg)-negative patients with a clinical diagnosis of chronic liver disease (60 patients) and hepatocellular carcinoma (HCC) (14 patients) were assayed for anti-HCV antibody by second generation enzyme immunoassay and 48 were confirmed anti-HCV-positive (33 males, 15 females). Other causes of chronic liver disease (e.g. haemochromatosis, Wilson's disease and immune-mediated injury) were ruled out. Liver biopsy was done in 27/48 anti-HCV-positive patients and in all HCC patients. Genotypes were determined for 45/48 anti-HCV-positive study patients; 39/45 (87%) were type 3; four (9%) were type 1; one was type 2; and one was type 5. Past blood transfusion was the main identifiable risk factor found in 10 patients, all type 3. Seven of the 14 HCC patients were anti-HCV positive, (six were type 3). Most patients with hepatitis C presented with established cirrhosis and complications of portal hypertension and liver failure. IN CONCLUSION: (i) genotype 3 is the most common isolate in HCV-associated chronic liver disease in Pakistan; (ii) a significant proportion of HBsAg-negative cirrhotics are non-B, non-C in aetiology; and (iii) half of the patients with HCC have serological evidence of HCV infection.

Adult↗
PubMed1996

Suppression of T cell proliferation by tumor-induced granulocyte-macrophage progenitor cells producing transforming growth factor-beta and nitric oxide.

Production of high levels of granulocyte-macrophage CSF (GM-CSF) by LLC-LN7 tumors results in myelopoietic stimulation and an increase in cells having natural suppressor (NS) activity. Prior studies showed these NS cells could be isolated from the bone marrow of tumor-bearing mice with an Ab (ER-MP12) that recognized GM-progenitor cells. The present study showed these cells to also be in the spleen, lymph node, and tumor, and that treatment of tumor-bearing mice with low doses of IFN-gamma plus TNF-alpha reduced the frequency of E-MP12+ cells. Studies focused on characterizing the intratumoral ER-MP12+ cells and the mechanism by which they suppress T cell proliferation. When isolated and seeded in soft agar with CSF-containing LLC-LN7 supernatants, the ER-MP12+ cells grew into colonies, most of which contained both granulocytic and monocytic cells. Tumor-derived ER-MP12+ cells and their culture supernatants were suppressive to T cell proliferation. Among the factors produced by ER-MP12+ cells were TGF-beta, nitric oxide (NO), IL-10, and prostaglandin E2 (PGE2). However, it was TGF-beta and NO that mediated the suppression of T cell proliferation by ER-MP12+ cells. Intratumoral ER-MP12+ cells could be maintained as suppressive blastlike cells for at least 4 days in cultures containing CSFs, but adding IFN-gamma plus TNF-alpha to these cultures caused their differentiation mainly into nonsuppressive TNF-alpha-secreting monocytic cells. These results show that intratumoral ER-MP12+ cells having homology to GM-progenitor cells suppress T cell function by producing TGF-beta and NO. IFN-gamma/TNF-alpha treatment stimulates their differentiation and shift from production of TGF-beta and NO to production of TNF-alpha.

Animals↗
PubMed1996

Ethnic differences in public health awareness, health perceptions and physical exercise: implications for heart disease prevention.

OBJECTIVES: To study whether the wide differences in heart disease incidence amongst ethnic groups in the UK, with the higher mortality and morbidity in peoples of south Asian descent, may be attributed to differences in public health awareness and life-style. DESIGN: Questionnaire-based survey of women from different ethnic groups attending an antenatal clinic in a city centre district general hospital. RESULTS: We surveyed 232 housewives from 3 different ethnic groups: 84 white (mean age 24.3 years +/- standard deviation (SD) 5.84), 76 Afro-Caribbean (mean age 24.7 years +/- SD 4.46) and 72 Asians (defined as people of south Asian or Indian subcontinent descent; mean age 25.7 years +/- SD 5.5). The proportions of smokers amongst the whites, blacks and Asians were 38.1%, 27.6% and 2.8% respectively. Proportions consuming alcohol regularly were 31.0%, 10.5% and 4.2% respectively. A higher proportion of blacks reported a change in dietary fibre intake, whilst a higher proportion of whites reported a change in dietary fat intake and sugar intake as a result of public health campaigns, publicity or advertising. There was a significantly lower proportion of reported regular exercise activity amongst the Asian women and their husbands or partners. CONCLUSION: This study demonstrates that Asian families were the least likely to take regular exercise, and had a lower awareness of cholesterol or dietary content (fibre, sugar, salt) despite public health campaigns and publicity. They were however the least likely to smoke cigarettes. These ethnic differences may in part explain the higher prevalence of coronary heart disease amongst the Asian population in the UK. This ethnic group should be targeted for intense public health intervention, education and other preventative measures to reduce the risks of heart disease.

Attitude to Health↗
PubMed1995

Dietary fat purchasing habits in whites, blacks and Asian peoples in England--implications for heart disease prevention.

The mortality and morbidity from coronary heart disease (CHD) is higher in people of South Asian origin than in whites, but is significantly lower in the black (Afro-Caribbean origin) community in the United Kingdom. To investigate whether this may be related to differences in fatty food intake, we performed a questionnaire survey of the weekly food purchasing habits and preparation methods in white, black (Caribbean) and Asian households in Birmingham. We interviewed 224 housewives from three ethnic groups (84 white, 76 black/Afro-Caribbean and 72 Asian). The highest quantity of fat in foods purchased per week was found in the Asian population (median 1409 g/week per person, interquartile range (IQR) 850-1952), which was significantly greater than black subjects, who had the lowest quantity of fat in foods purchased (1012 g/week per person, IQR 835-1388) (Mann-Whitney test:median differences 300.5, 95% C.I. 23.3-600.4, P = 0.029). The median quantity of fat in foods purchased by the white households was intermediate, at 1186 g/week per person (IQR 861-1711). There was a higher quantity of fat in foods purchased in the lower social classes (IV and V) in both the white and Asian populations. Butter, egg and milk consumption was significantly greater in Asians; with ghee consumption almost exclusive amongst this group (98%). Amongst whites and blacks, the commonest food preparation methods were grilling, boiling or poaching; whilst amongst Asians, frying was more common (chi 2 = 81.25, d.f. = 4, P < 0.0001).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗