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Biomedical subjects

M Khan

Publications and source records attributed to M Khan.

At least 163 records · Page 9Linked to original sources

Typhoid fever and asymptomatic human immunodeficiency virus infection. A report of 10 cases.

Ten patients with asymptomatic human immunodeficiency virus (HIV) infection were treated for typhoid fever at King Edward VIII Hospital, Durban, South Africa, from 1993 through 1995. The mean age was 23.7 years (range, 8-33 years), with a female-to-male ratio of 9 to 1 and mortality and morbidity rates of 20% and 10%, respectively. Common presenting manifestations were fever (100%), relative bradycardia (50%), and diarrhea (40%). With respect to epidemiologic and clinical characteristics, we noted no significant differences among these 10 HIV-positive and 32 HIV-negative patients treated for typhoid fever during the same period. However, we found hepatic dysfunction in the form of an isolated increase in aspartate aminotransferase (p < 0.01) and abnormal urinary findings suggestive of glomerulonephritis (p = 0.01) more frequently in HIV-positive patients.

Adolescent↗

Cytomegalovirus in transplantation: new developments.

The control of cytomegalovirus infection and disease continues to be a major problem in transplantation and different strategies have been developed to reduce its incidence. Early diagnosis of infection soon after transplantation, using molecular tools such as the polymerase chain reaction, have resulted in successful clinical trials using the strategy of pre-emptive therapy. Adoptive transfer of immune cells, which are predominantly the cytomegalovirus-specific cytotoxic T lymphocytes, into transplant recipients has been shown to restore effective immunity. A vaccine preparation has been in development aimed at preventing primary infections in allograft recipients though effective protection has yet to be shown. The mechanisms of viral pathogenesis in chronic graft rejection remain unclear; however, recent contributions from the field of cell biology have increased our understanding of possible processes which have the potential for application in the field of gene therapy for the treatment of disease.

Antiviral Agents↗

Acute compartment syndrome--presenting as severe pain in an extremity out of proportion with the injury.

A 24 year old combat medic was admitted to the field hospital at Tomislavgrad in Bosnia, with a suspected forearm, fracture. Radiographs did not show any bony injury. Clinical examination showed marked swelling and tenderness over the extensor compartment. The pain became more severe over the following 12 hours with the pain becoming most intensely felt in the extensors on passive extension. Fasciotomy for suspected acute compartment syndrome was carried out. Acute compartment syndrome is a common complication of extremity injury, and is a clinical diagnosis which should be suspected in all injuries with marked swelling and severe pain.

Accidental Falls↗

AIDS: safety, regulation and the law in procedures using blood and blood products.

The purpose of this paper is to examine issues of regulation of the market for, and use of, blood and blood products. The situation has changed since the discovery of the Human Immune Deficiency Virus (HIV), the presumed cause of AIDS, because it was recognized that some haemophiliacs were infected with HIV from transfused blood and blood products before 1985. When the danger was realized in that year, regulations were introduced internationally to prevent this, but meanwhile some haemophiliacs developed AIDS. In several countries, governments have accepted responsibility, without liability, for possible transmission of infection, and paid compensation to victims. In France three health service officials have been convicted of fraud and criminal negligence. In March 1997 a trial began in Japan of three drugs company executives accused of promoting the sale of HIV-contaminated blood products. Since then there has been a class action in the USA resulting in awards. Further issues have arisen with regard to the outcome and treatment of asymptomatic infection with HIV. The implications for public safety, and for medical and legal practice, are far reaching and reveal a need for more effective monitoring of the existing procedure for supply and clinical use of blood and blood products.

Acquired Immunodeficiency Syndrome↗

Ingested IFN-alpha has biological effects in humans with relapsing-remitting multiple sclerosis.

Parenterally administered human recombinant type I interferons (hrIFN) in relapsing-remitting multiple sclerosis (RRMS) decrease relapses and spontaneous in vitro IFN-gamma production, reduce clinical progression, and decrease magnetic resonance imaging (MRI)-defined disease activity and lesions. Parenterally administered type I IFN use is limited by clinical and chemical toxicities, and the induction of antibodies that abrogate their activity in vivo correlated with the loss of clinical benefit. Therefore, we determined whether ingested IFN-alpha was non-toxic and had biological effects in humans. Ingested hrIFN-alpha showed no toxicity in normal volunteers or patients with RRMS at doses ranging from 300 to 100,000 units. In subjects with RRMS, a significant decrease in Con A-mediated proliferation and serum soluble intercellular adhesion molecule-1 (sICAM-1), a surrogate measure for disease activity in MS, was found after ingesting 10,000 and 30,000 units IFN-alpha The RRMS subjects also showed decreased IL-2 secretion after ingesting 10,000 units IFN-alpha and decreased IFN-gamma, TGF-beta and IL-10 production after ingesting 30,000 units IFN-alpha. The decreased secretion of IFN-gamma and IL-2 by ingested IFN-alpha suggests that oral IFN-alpha may cause a functional inhibition of Th J-like T helper cells in RRMS, a potential site of intervention at the level of effector T cells in MS. Our studies support the oral use of human IFN-alpha as a biological response modifier in humans.

Administration, Oral↗

Body composition and health-related quality of life in patients with obstructive airways disease.

This study evaluated the effects of body weight and lean mass abnormalities on health-related quality of life (HRQL) in obstructive airways disease. Body weight, lean mass (using dual-energy X-ray absorptiometry), and HRQL (using the St George's Respiratory Questionnaire (SGRQ)) were measured in 50 patients. Low lean mass was defined as a lean mass index (lean mass/height2) below the fifth percentile of a control population. Dyspnoea was measured by the baseline dyspnoea index. The mean (SD) age was 69+/-9 yrs; the forced expiratory volume in one second (FEV1) was 39+/-19% of predicted. Patients had 2.4+/-4.1 kg less lean mass than predicted. Increased dyspnoea was the most influential predictor of poor HRQL. Compared to normal-weight patients, those who were underweight had significantly greater impairment in activity, impact, and total SGRQ scores, while those who were overweight had greater impairment in impact and total SGRQ scores. Low lean mass was associated with greater impairment in symptoms, activity and impact subscores and the total SGRQ score. When dyspnoea was added to the model as a covariate, neither weight nor lean mass remained significantly related to HRQL. Thus, although body weight and lean mass abnormalities influence health-related quality of life, their effects appear to be mediated through increased levels of dyspnoea.

Absorptiometry, Photon↗

IFN-beta 1b treatment of relapsing multiple sclerosis has no effect on CD3-induced inflammatory or counterregulatory anti-inflammatory cytokine secretion ex vivo after nine months.

Multiple sclerosis (MS) is presumed to be a T-cell mediated chronic inflammatory disease of the central nervous system. We have previously reported that IFN-beta 1b (Betaseron) decreases CD3-mediated TNF-alpha secretion but increases another inflammatory cytokine, IL-6 after three months of treatment. We have now examined cytokine secretion of peripheral blood mononuclear (PMNC) cells after stimulation with OKT3 (anti-CD3) monoclonal antibody (mAb) or Con A in subjects with clinically stable relapsing MS before and three, six and nine months after initiating IFN-beta 1b treatment. At nine months Con A-induced TNF-alpha secretion decreased significantly below baseline but IFN-gamma secretion increased above baseline. There were no significant changes in Con A-induced IL-4 over the six month period and no changes in IL-10 and IL-2 over the nine month period. After nine months on treatment the CD3-induced TNF-alpha and IFN-gamma secretion was not significantly different from the original baseline values. Increased CD3-mediated IL-6 secretion in on-treatment compared to pre-treatment samples at three months gradually declined to baseline values by nine months on-treatment. There was no significant changes from baseline compared to nine months on-treatment in CD3-mediated IL-2, IL-4, IL-10. IFN-beta 1b (Betaseron) treatment has no clear persistent effect on CD3-induced inflammatory or counterregulatory anti-inflammatory cytokine secretion.

Adult↗

Increased in vitro induced CD4+ and CD8+ T cell IFN-gamma and CD4+ T cell IL-10 production in stable relapsing multiple sclerosis.

Multiple sclerosis (MS) is presumed to be a T-cell mediated chronic inflammatory disease of the central nervous system. Investigators previously demonstrated increased IFN-gamma (pro-inflammatory) and IL-10 (counterregulatory anti-inflammatory) in MS. The balance of pro-inflammatory and counterregulatory anti-inflammatory cytokines may be important in the stabilization of disease activity. Purified CD4+ and CD8+ T cells from patients with clinically definite, stable relapsing MS (RRMS) were stimulated by anti-CD3 mAb or Con A for 48 hours and cytokine supernatants analysed for production of IL-2, IL-6, IFN-gamma, TNF-alpha (potential pro-inflammatory) and IL-4, IL-10, and TGF-beta (potential counterregulatory anti-inflammatory). Con A activated CD4+ and CD8+ T cell proinflammatory cytokine IL-2 secretion, CD4+ T cell IL-6 secretion, CD4+ and CD8+ T cell TNF-alpha secretion and CD8+ T cell IFN-gamma secretion was decreased significantly in RRMS subjects compared to controls. CD3 activated CD4+ and CD8+ T cell IL-6 secretion and CD4+ T cell TNF-alpha secretion was significantly decreased in MS subjects compared to controls. In contrast, there was increased CD3-induced IFN-gamma in both CD4+ and CD8+ T cells and counterregulatory anti-inflammatory CD3-induced IL-10 secretion in CD4+ T cells in RRMS compared to controls. These data suggest that an equilibrium of a pro-inflammatory (IFN-gamma) and a counterregulatory anti-inflammatory (IL-10) cytokine may define stable clinically definite early RRMS.

CD3 Complex↗

Etiology and clinical profile of hepatocellular carcinoma in Bangladesh.

Sixty-four consecutive subjects with hepatocellular carcinoma were prospectively studied in the department of Hepatology, IPGMR, Dhaka. Their mean age was 50.11 years. Fifty-two were male and 12 female. Cirrhosis was present in 12 (18.75%) subjects. Thirty subjects (46.88%) had HBsAg in their sera. Seven (58.33% of females) patients gave history of use of oral contraceptives. Cirrhosis, HBV infection, male sex, middle age, and probably the use of oral contraceptives in females appeared to be important risk factors for development of HCC in Bangladesh. Majority of patients presented with upper abdominal pain, weight loss and anorexia. Hepatomegaly was invariably present. Alpha fetoprotein was significantly higher in cirrhotic HCC patients than in non-cirrhotic ones. Median survival was two months. None of the clinical or laboratory features predicted the prognosis.

Adult↗

Correlative studies of heart rate and heart rate variability indices from five consecutive ambulatory electrocardiogram recordings in patients with coronary artery disease.

BACKGROUND: Reproducibility of heart rate (HR) and heart rate variability (HRV) indices from ambulatory electrocardiograms (AECGs) is a prerequisite for their use as predictors or monitors of disease progression, or response to therapeutic interventions. HYPOTHESIS: This study sought to determine the stability over time of HR and HRV indices in patients with coronary artery disease. METHODS: Five AECGs, recorded at 1-week intervals in 21 clinically stable patients, were used to calculate minimum, average, and maximum HR, and three commonly used HRV indices in data samples of 15, 30, 60, 120, daytime and nighttime intervals (complete data were available on 17 patients). RESULTS: All parameters studied were stable over time (p = NS). Diurnal variation was found only for the average and maximum HR, with values being higher for daytime than for nighttime. Intercorrelations of the HR and HRV indices were poor and varied among the five AECGs, suggesting that these parameters reflect different aspects of HRV. The HR and HRV variables calculated from short-time intervals correlated poorly with the corresponding information from 24-h recordings, and such relationships varied among the five AECGs. CONCLUSIONS: Thus, HR and HRV indices from five consecutive AECGs recorded at 1-week intervals are reproducible. The poor intercorrelations between pairs of the studied indices suggest that none of these parameters can be used as surrogate of the others. Finally, the poor performance of HR and HRV indices, deriving from short-time intervals, indicate that they cannot be employed in lieu of parameters calculated from 24-h AECGs.

Aged↗

Oral administration of IFN-alpha is superior to subcutaneous administration of IFN-alpha in the suppression of chronic relapsing experimental autoimmune encephalomyelitis.

We have previously demonstrated that type I IFNs administered orally (p.o.) suppress clinical relapse in murine chronic relapsing experimental autoimmune encephalomyelitis (CR-EAE), inhibit clinical attacks at doses equivalent to ineffective parenteral (s.c.) doses in acute rat EAE, and decrease the adoptive transfer of EAE. We therefore examined the optimal clinical p.o. dose of murine species-specific IFN-alpha for suppression of relapse attacks and compared it to s.c. administered IFN-alpha in a dose-response experiment in the chronic EAE model. The optimal clinically effective dose for suppression of EAE of p.o. administered murine species-specific IFN-alpha was 10 units and for s.c. administered was 100 units, although the optimal p.o. dose was much more clinically effective than the optimal s.c. dose. Con A- and MT-induced spleen cell proliferation was inhibited by p.o. IFN-alpha, as was Con A-induced IL-2 secretion, but s.c. IFN-alpha did not inhibit the Con A-induced proliferation in spleen cells. Oral IFN-alpha inhibited the mitogen-induced production of IL-2 and IFN-gamma, but s.c. IFN-alpha increased MT-induced IFN-gamma and IL-6 secretion in spleen cells and Con A-induced IL-6 and MT-induced IL-2 and IL-6 in lymph node cells. The oral route is a convenient drug delivery system that may allow the use of lower doses of cytokines and provide enhanced efficacy via unique and potent immunoregulatory circuits without generating additional inflammatory cytokines that may counteract the beneficial effects of s.c. administered type I IFNs.

Administration, Oral↗

The biologic role of B2 integrins in the host response to expanded polytetrafluoroethylene.

We hypothesized that the adherence of leukocytes to a vascular graft surface is mediated by B2 integrins. We studied integrin expression and monoclonal antibody inhibition of peripheral blood leukocyte (PBL) binding in vitro and CD11b expression in vivo. Human PBL were grown on ePTFE in culture and labeled with monoclonal antibodies to CD11a, -b, -c, and/or CD18. Percentage of monoclonal antibody binding and inhibition of leukocyte adherence was studied for up to 30 min using flow cytometry. ePTFE segments were implanted subcutaneously in SH-1 mice and PBL harvested 4 days later. PBL binding of monoclonal antibodies against CD11b was measured using flow cytometry. CD18 was constitutively expressed and CD11a decreased over time. CD11b increased from 41 to 62% and CD11c increased transiently (P < 0.003, P < 0.005). Inhibiton of PBL adherence was greatest by CD11b (34%) and CD11b + CD18 (57%) (P < 0.005, P < 0.0025). Implanted ePTFE caused a fourfold increase in PBL monoclonal antibody binding of CD11b (P < 0.001) compared to sham, Staphylococcus aureus alone, and combination of ePTFE and S. aureus. In conclusion, leukocyte integrins play a central role in the interaction between PBLs and ePTFE as measured by binding of monoclonal antibodies and inhibition of PBL adherence. This is also true in vivo since PBL increase CD11b expression four times when ePTFE is compared to sham. These observations indicate a potential role in vivo for B2 integrins in vascular prosthetic infections.

Animals↗

Lack of neurotoxic effect of diethylpropion in crack-cocaine abusers.

Dopamine agonists have been used with some success in treating cocaine addiction. However, both cocaine and psychostimulants have been reported to produce neurotoxic effects. We evaluated the effect of the stimulant diethylpropion on cognitive performance in a double-blind, placebo-controlled trial. Forty-six abstinent crack-cocaine users received either placebo, 25-mg, 50-mg, or 75-mg doses of diethylpropion. Patients were tested at baseline and again after 9-14 days of medication. There were no differences between placebo and medication groups on any test, indicating that, within the time frame studied, diethylpropion does not produce neurotoxic effects that can be detected with standardized neuropsychological tests.

Adult↗

Enterovirus infection of the central nervous system of humans: lack of association with chronic neurological disease.

We have searched, using a sensitive nested-PCR, for enterovirus RNA in cerebrospinal fluid and post mortem central nervous system (CNS) tissue from patients with previous poliomyelitis with or without late functional deterioration, patients with motor neuron disease (MND), and control patients with other neurological disease or without neurological disease. Enterovirus RNA was detected in patients with previous poliomyelitis and MND, but also in control patients with and without neurological disease. Our results do not provide any evidence that such enterovirus infection is related to late functional deterioration in patients with previous poliomyelitis, which could be attributed to other medical conditions in most instances, and do not support the hypothesis that MND is associated with enterovirus infection of the CNS. Nucleotide sequence analysis of enterovirus RNA sequences detected indicated that enteroviruses detected were of the non-polio type.

Adult↗

Acromegaly presenting with diabetic ketoacidosis.

Diabetes in acromegaly is usually non-insulin dependent and is secondary to insulin resistance caused by growth hormone excess. Diabetic ketoacidosis is a result of relative insulin deficiency and is a rare feature of acromegaly. We describe a case of acromegaly presenting with diabetic ketoacidosis. We demonstrate that growth hormone excess can cause diabetic ketoacidosis in the presence of relative, but not absolute insulin deficiency.

Acromegaly↗

Treatment of neonatal seizures with carbamazepine.

Carbamazepine has been used in adults and children for over 30 years. In spite of an excellent therapeutic and side-effect profile in older children, it has never been used as a primary anticonvulsant in neonates. This is the first report of the long-term use of carbamazepine in neonates. Ten full-term neonates with two or more seizures due to hypoxic-ischemic encephalopathy were given 10 mg/kg of carbamazepine as a loading dose via nasogastric tube. Twenty-four hours later, the first five patients began a maintenance regimen of 21 mg/kg/daily, and the remaining five patients began a maintenance regimen of 15 mg/kg/daily, all via nasogastric tube. Therapy was continued for 3 to 9 months. Drug levels were monitored every 2 to 4 hours during the first 24 hours, and on days 2, 4, 8, 15, 30, 45, and 60, and monthly thereafter. Absorption of carbamazepine was excellent even in sick neonates. Therapeutic levels were reached in 2 to 4 hours in all patients. Peak levels were achieved in 4 to 16 hours (mean, 9.2 +/- 4.2). Elimination half-life was 24.5 hours. Levels dropped precipitously around 8 to 15 days and thereafter declined slowly over the next 3 months. Seizure control was excellent; only two patients had one seizure each during the first 10 hours. There were no gastrointestinal, hepatic, hematologic, renal, or dermatologic side effects. This preliminary study shows that carbamazepine may be an effective anticonvulsant for neonatal seizures.

Carbamazepine↗