Biomedical subjects

M Hussain

Publications and source records attributed to M Hussain.

At least 127 records · Page 7Linked to original sources

PubMed1997

Serum free IGF-I during a hyperinsulinemic clamp following 3 days of administration of IGF-I vs. saline.

In a randomized crossover study in eight healthy subjects, we compared the effect of 3 days of continuous subcutaneous administration of insulin-like growth factor I (IGF-I; 10 micrograms.kg-1.h-1) and saline on fasting serum levels of free IGF-I, total (extractable) IGF-I, and IGF-binding protein (IGFBP)-1 and -3. On the 3rd day a hyperinsulinemic (euglycemic and hypoglycemic) clamp was performed. When preclamp (baseline) levels were compared after 3 days, IGF-I administration had increased total IGF-I from 225 +/- 21 (means +/- SE) to 1,003 +/- 46 micrograms/l (P < 0.0001), free IGF-I from 0.5 +/- 0.2 to 10.4 +/- 1.7 micrograms/l (P < 0.001), IGFBP-3 from 2,908 +/- 148 to 3,591 +/- 179 micrograms/l (P < 0.01), and IGFBP-1 from 7.6 +/- 3.8 to 19.6 +/- 2.5 micrograms/l (P < 0.01). During the clamp, levels of free IGF-I increased gradually from baseline to 1.0 +/- 0.3 micrograms/l (saline; P < 0.01) and to 19.6 +/- 4.7 micrograms/l (IGF-I; P < 0.005). Concomitantly, levels of IGFBP-1 decreased gradually from baseline to 4.1 +/- 2.3 micrograms/l (saline; P < 0.0005) and to 4.6 +/- 1.8 micrograms/l (IGF-I; P < 0.0001). Total IGF-I exhibited minor changes only during the clamp (P < 0.05), and IGFBP-3 was unchanged. In conclusion, administration of IGF-I increased total IGF-I about fourfold, whereas free IGF-I increased 20-fold. Noteworthily, in both situations a further twofold increase in free IGF-I was observed during the hyperinsulinemic clamp, concomitant with a decrease in IGFBP-1. This supports the hypothesis that IGFBP-1 is important in the short-term regulation of free IGF-I in vivo.

Adult↗

PubMed1997

Rate-dependent abbreviation of Ca2+ transient in rat heart is independent of phospholamban phosphorylation.

The mechanisms underlying the accelerated decline of the intracellular Ca2+ transient that occurs in cardiac muscle when stimulation rate is increased have been investigated in ventricular myocytes from rat hearts. Increasing stimulation rate from 0.1 to 0.5 and 1 Hz decreased the time taken for the Ca2+ transient to decline from its peak to 50% of its peak value in cells generating action potentials, when the duration of depolarization was held constant by voltage clamp, and when Na/Ca exchange was inhibited. The sarcoplasmic reticulum Ca2+ adenosinetriphosphatase inhibitor thapsigargin inhibited rate-dependent abbreviation of the Ca2+ transient. However, neither a chemical inhibitor of Ca(2+)-calmodulin-dependent protein kinase II (KN62) nor a peptide inhibitor of this enzyme (calmodulin-binding domain peptide) had a significant effect on rate-dependent abbreviation of the Ca2+ transient. Analysis of the phosphorylation of the regulatory sites Ser16 and Thr17 of phospholamban showed no significant change in phosphorylation with changes of stimulation rate. These data suggest that rate-dependent shortening of the Ca2+ transient is due predominantly to enhanced Ca2+ uptake by the sarcoplasmic reticulum without changes in phospholamban phosphorylation.

Action Potentials↗

PubMed1997

Evaluation of adrenal function in long standing pulmonary tuberculosis: a study of 100 cases.

Tuberculosis is a major public health problem in Pakistan and adrenal involvement in long-standing tuberculosis has been found to be common. A multi-center study was conducted to assess the adrenal function using short Synacthen test in one hundred patients with tuberculosis of more than 6 months duration at three hospitals of Rawalpindi and Islamabad. Forty patients demonstrated impaired response to Synacthen test. In 21 (52.5%) the increment from basal level was less than 300 nmol/L with a peak level increasing to over 600 mmol/L in 15 (37.5%) patients, the increment from basal level was less than 300 nmol/L as well as the peak level was also less than 600 nmol/L. In 4 (10%) patients the increment was more than 300 nmol/L but they were not able to obtain a peak level of 600 nmol/L. No significant difference was found between the patients with normal response and the impaired response with regards to their clinical features, duration of illness, body mass index (BMI), blood pressure variation and routine biochemical profile. It is concluded that adrenal dysfunction is common in patients with long-standing tuberculosis. Diagnosis of hypoadrenalism is not possible on clinical grounds and routine biochemical examinations. Synacthen stimulation test is necessary for its diagnosis.

Adrenal Cortex Diseases↗

PubMed1997

Prostate cancer clinical trials of the Southwest Oncology Group.

The changing clinical dynamics of prostate cancer have resulted in a broadening of the research focus of the Genitourinary (GU) Cancer Committee of the Southwest Oncology Group (SWOG). Beginning with an emphasis on hormone-refractory disease in its early years, SWOG prostate cancer trials now cover the entire spectrum of the disease: localized, locally advanced, metastatic and hormone-refractory disease. As the world's largest GU cancer research group, the GU committee of SWOG has pioneered studies in combined androgen therapy for metastatic disease, quality-of-life (QOL) assessments for patients with localized and advanced disease, adjuvant therapy models, and prostate cancer chemoprevention. The committee has also formed the GU Global Group, whose purpose is to convene the chairs of the GU committees of all the major national and international oncology cooperative groups. Meeting semiannually, this group discusses activities within their respective organizations, plans collaborative strategies and protocols, and establishes global strategy in prostate cancer clinical research. The future directions of national and international prostate cancer trials will build on this broad foundation of well-conceived, logically sequenced studies.

Androgen Antagonists↗

PubMed1997

Prediction of renal function recovery in obstructive renal failure due to stones.

Two hundred and thirty-nine patients with renal and ureteric calculi associated with renal failure were evaluated for recovery potential before definitive surgery. Ultrasonography was carried out pre-operatively in all, followed by percutaneous nephrostomy (PCN) as an initial management before definitive surgery. Diethylene triamine penta acetic acid (DTPA) scan was done in 125 patients after percutaneous nephrostomy, findings of pre- operative DTPA scan were correlated with post-operative drop in serum creatinine. Urine pH, urine Na+, initial diuresis, creatinine clearance and serum creatinine were measured serially after 24 hours and then every week for 6 weeks. Patients were re-evaluated with serum creatinine after 3 months of surgery. Ultrasonography was found to be reliable in predicting future recovery of renal functions in 76.5% cases and true obstruction of shorter duration (F4-group) on DTPA scan in 81.9% cases. Urine pH of 6 or less, post-PCN diuresis and natriuresis were good prognostic indicators. PCN was found to be most reliable method of predicting future recovery of renal function after relief of obstruction with 97.8% accuracy.

Adult↗

PubMed1997

Paclitaxel, cisplatin, and 5-fluorouracil in patients with advanced or recurrent squamous cell carcinoma of the head and neck: a preliminary report.

The combination of 5-fluorouracil (5-FU) and cisplatin is considered the most active chemotherapy for patients with recurrent squamous cell carcinoma of the head and neck (SCCHN), with an overall response rate of 30%. Paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) has demonstrated activity in SCCHN and synergy with cisplatin. To augment the activity of the combination of 5-FU and cisplatin, a pilot study was designed to determine the feasibility of combining 3-hour infusional paclitaxel with 5-FU and cisplatin. To be eligible, patients had to have recurrent or advanced SCCHN with measurable or evaluable disease and no prior chemotherapy. A minimum of three courses had to be delivered to determine cumulative toxicity. The starting dose level consisted of paclitaxel 135 mg/m2 on day 1, cisplatin 75 mg/m2 on day 2, and 5-FU 1 g/m2 on days 2 through 6. The first treated patient developed grade 4 mucositis, which resulted in reducing dose level 1 of 5-FU to 800 mg/m2/d on days 2 through 6 (seven patients); subsequently, the 5-FU dose was adjusted to 1 g/m2/d on days 2 through 5 (nine patients). To date, 17 patients have been enrolled, with a median age of 62 years (range, 48 to 75 years). Of the 17 patients, nine had recurrent disease following prior surgery and/or radiotherapy and eight had previously untreated advanced SCCHN. Major toxicities were neutropenia and mucositis. There were four early deaths (two treatment-related and two cancer-related). Forty-seven courses of therapy were delivered, with a median of two (range, one to five). The overall response rate in 14 response-evaluable patients was 71% (10 of 14 patients; eight partial and two complete responses). Five of seven response-evaluable patients with recurrent disease had major responses (one complete and four partial responses). At the current dose, the combination of paclitaxel/5-FU/cisplatin is feasible and shows very encouraging activity, particularly in patients with recurrent SCCHN.

Aged↗

PubMed1997

A phase II study of carboplatin and paclitaxel in the treatment of patients with advanced esophageal and gastric cancer.

We initiated a phase II study to determine the efficacy of carboplatin and paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) in patients with advanced esophageal or gastric cancer. Objective tumor responses, duration of response, time to disease progression, overall survival, and toxicity profile are the end points evaluated in this study. The study includes patients with locally advanced metastatic or recurrent esophageal or gastric cancer with no history of prior chemotherapy or radiation treatment. Patients are required to have a performance status of 0 to 2 and no organ failure. Staging diagnostics include computed tomography scans and endoscopic ultrasound when appropriate. Starting dose of paclitaxel is 200 mg/m2, and carboplatin is given to achieve an area under the concentration-time curve of 5.0. Dose escalation is attempted if nadir counts permit. Seventeen patients have registered so far. Of those, three are not evaluable for efficacy analysis: one has not been on study long enough to be assessed for response and the other two are not assessable for objective tumor response. Three patients with gastric cancer have achieved partial responses. Two of five patients with esophageal cancer responded (partial response) to this treatment. Dose escalation by one step was feasible in approximately half the patients. There were no episodes of neutropenic fever. Carboplatin and paclitaxel given on an outpatient basis is well tolerated and an interesting regimen for the treatment of patients with advanced gastric or esophageal cancer.

Adult↗

PubMed1996

Prostate cancer: flow cytometric methods for detection of bone marrow micrometastases.

Up to 60% of patients with clinically localized prostate cancer will relapse despite potentially curative local treatment. Current staging tests have been limited in adequately identifying individual patients who are at a high risk for future relapse. Detection of bone marrow micrometastases may identify individuals destined to develop clinically detectable systemic metastases. Although immunohistochemistry and molecular approaches are being investigated, the most ideal test(s) are yet to be determined. In this report we describe methods for specific detection and isolation of prostate cancer micrometastases by multi-parameter rare event flow cytometric analysis. A model was developed and validated using three human prostate cancer cell lines, healthy donor marrow, dual marker labeling for cytokeratin (epithelial-specific marker) and CD45 (bone marrow-specific marker). The detection sensitivity of this model was at the level of one prostate cancer cell in 100,000 nucleated bone marrow cells. As a part of an ongoing clinical study, bone marrow aspirates from 15 patients with newly diagnosed prostate cancer have been analyzed. Six patients were found to have cytokeratin positive/CD45 negative cells in their bone marrow aspirates. We conclude that flow cytometric rare event analysis provides a sensitive and specific assay for detection of bone marrow micrometastases in patients with clinically localized prostate cancer.

Bone Marrow Neoplasms↗

PubMed1996

Prospective survey of the incidence, risk factors and outcome of hospital-acquired infections in the elderly.

Four hundred and thirty-six patient admissions to either an acute assessment or a rehabilitation ward for the care of the elderly were studied. A total of 113 episodes fitting the definition of a hospital-acquired infection (HAI) occurred in 81 (18.5%) of admissions. The global infection rate was 10.8 per 1000 patient bed days and did not differ between the wards. The chest and urinary tract were the commonest sites of infection, and 26 patients appeared to be infected at more than one site. The majority of first infections occurred within 14 days of admission. Median length of stay for patients with one or more infective episodes was significantly longer than for those who did not develop an HAI. The presence of an HAI, multiple-site infections and chest infections were significantly associated with fatal outcome. HAI occurs commonly in elderly patients and is associated with prolonged hospital stay and increased mortality.

Adult↗

PubMed1996

Dowry cannibalism.

The term dowry cannibalism is used in this article to describe a unique case where the motive for cannibalism was the non-fulfilment of a husband's dowry demands from his wife. The husband was accused by the wife of regularly using a syringe to withdraw blood from her, with the intent of causing her death, and drinking it. Intriguing as this is, it is also medicolegally important: this method of killing might leave no trace suggesting murder. It is postulated that this form of abuse may also significantly alter the psychological state of the victim and hasten death. The case is not yet concluded, and may never be, thus details to allow identification have been omitted from the report.

Journal Article↗

PubMed1996

Interferon-alpha 8b is the only variant of interferon-alpha 8 identified in a large human population.

Three variants of human interferon (IFN)-alpha 8a gene, that is, IFN-alpha 8b, and IFN-alpha 8c, have been reported previously. They differ from each other by changes in their coding region at nucleotide positions 359-360, 372, and 550. Human genomic DNA obtained from over 28,000 healthy blood donors and from 4 human cell lines was used in the polymerase chain reaction (PCR) designed for specific amplification of the IFN-alpha 8 gene fragments. The resulting PCR product was analyzed by (1) restriction endonuclease digestion, (2) DNA sequencing, and (3) allele-specific secondary PCR amplification. Only one sequence for IFN-alpha 8 was identified, and that was for IFN-alpha 8b. The sequences for IFN-alpha 8a and IFN-alpha 8c were not detected after PCR amplification either in the pooled leukocytes obtained from > 28,000 individuals or in cell lines tested. These data suggest that the naturally occurring variant or allele for IFN-alpha 8 in the population is IFN-alpha 8b. IFN-alpha 8a and IFN-alpha 8c variants were consistently below the level of detection of the assays and, if present at all in the population, are very rare.

Alleles↗

PubMed1996

Identification of interferon-alpha 7, -alpha 14, and -alpha 21 variants in the genome of a large human population.

The genes for type I interferon (IFN), which include 14 IFN-alpha genes, 1 IFN-beta gene, 1 IFN-omega gene, and a number of IFN-omega pseudogenes, are clustered on human chromosome 9. Among IFN-alpha genes, a number of variants have been reported. Three variants of IFN-alpha 7 (IFN-alpha 7a, IFN-alpha 7b, and IFN-alpha 7c) and IFN-alpha 14 (IFN-alpha 14a, IFN-alpha 14b, and IFN-alpha 14c) and two variants of IFN-alpha 21 (IFN-alpha 21a and IFN-alpha 21b) are identified. The variants differ from each other by base changes in the coding region and can be distinguished by selective restriction enzyme analysis and DNA sequencing. We have used polymerase chain reaction (PCR) with IFN species-specific oligonucleotide primers for amplification of IFN-alpha 7, IFN-alpha 14, and IFN-alpha 21 gene sequences. Genomic DNA obtained from over 28,000 normal healthy individuals were collected in six pools for PCR amplification. To identify the presence of variant sequences, the resulting PCR products of specific IFN-alpha genes were analyzed by restriction endonuclease digestion and DNA sequencing, with a limit of detection of minor components to 1% and 10%, respectively. The results show that only one variant form for each of IFN-alpha 7, IFN-alpha 14, and IFN-alpha 21, namely, IFN-alpha 7a, IFN-alpha 14c, and IFN-alpha 21b, is detectable in the genomic DNA of the population examined. Similar results were obtained from the analysis of a human myeloblastoid cell line, KG-1.

Chromosomes, Human, Pair 9↗

PubMed1996

Novel nonpeptide antiplatelet glycoprotein IIb/IIIa receptor antagonist, DMP754: receptor binding affinity and specificity.

OBJECTIVE: To define the antiplatelet efficacy and specificity of the glycoprotein IIb/IIIa complex (GPIIb/IIIa) antagonist prodrug DMP754 and its free acid form, XV459. METHODS AND MATERIALS: DMP754 has an IC50 > 1 mumol/l, and, upon its conversion with esterases to its free acid form, demonstrated high potency (IC50 20-45 nmol/l) in inhibiting human platelet aggregation induced by 10 mumol/l adenosine diphosphate, 20 micrograms/ml collagen, 1 mmol/l epinephrine, 10 mumol/l platelet activating factor or 0.5 IU/ml thrombin. The in-vitro rate of hydrolysis of DMP754 or XV459 is much faster with human or canine liver esterases (t 1/2 = 2.4-23 min) than with plasma esterases (t 1/2 = 5.5-7.6 h). Platelet GpIIb/IIIa integrin binding affinity and specificity for XV459 were determined using cell binding/adhesion assays. RESULTS: The range of IC50 values of XV459 in inhibiting platelet aggregation in platelet-rich plasma obtained from 12 subjects was 0.035-0.069 mumol/l with a mean IC50 of 0.050 +/- 0.003 mumol/l. Additionally, XV459 inhibited platelets obtained from mongrel dogs, baboons, sheep, guinea pigs, and mice with IC50 in the range 0.024-0.06 mumol/l, and IC50 in the range 0.16-5.8 mumol/l in pigs, rabbits, and rats. XV459 inhibited [125I]-fibrinogen binding to activated human platelets with an IC50 of 0.011 +/- 0.003 mumol/l. XV459 demonstrated a high degree of selectivity in specifically inhibiting fibrinogen binding to the platelet integrin, GPIIb/IIIa (IC50 = 0.00025 +/- 0.00005 mumol/l) compared with inhibiting other integrins (alpha v beta 3, IC50 > 10 mumol/l; or alpha v beta 5, alpha 5 beta 1, or alpha 4 beta 1, for which the IC50 exceeded 100 mumol/l). CONCLUSION: DMP754 is a potent antiplatelet agent in inhibiting platelet aggregation, and has a high specificity and affinity for human platelet GPIIb/IIIa receptors.

Amino Acids↗

PubMed1996

Long-term follow-up of children inserted with T-tubes as a primary procedure for otitis media with effusion.

This study reviews 90 children who underwent T-tube insertion as a primary procedure for otitis media with effusion over a 3-year period and compares the long-term results with a similar group, matched in terms of age, treated with conventional Shepard grommets during the same period. Fifty-one patients (102 ears) in the T-tube group and 53 patients (106 ears) in the Shepherd grommet group attended for clinical review, a minimum of 6 years post-surgery. No significant difference was found between the two groups in terms of pre-operative symptoms (P = 0.95), operative findings (P = 0.84), hearing loss (P = 0.75), or degree of retraction or tympanosclerosis of the tympanic membrane (P = 0.80). A perforation rate of 24% in the T-tube group, compared with 2% in the Shepard grommet group (P = 0.001) is directly attributable to T-tube insertion. Furthermore, the risk of perforation was related to the duration of the ventilation tube in the tympanic membrane.

Case-Control Studies↗

PubMed1996

Dynamics of TGF-beta 3 peptide activity during rat alveolar epithelial cell proliferative recovery from acute hyperoxia.

Hyperoxia causes a reproducible pattern of lung injury and recovery, characterized by proliferation of type II alveolar epithelial cells (AEC2) during the recovery phase. We measured TGF-beta peptide production by AEC2 and macrophages from lungs of adult male rats exposed to 100% oxygen for 48 h and then allowed to recover for up to 72 h in room air. TGF-beta peptide activity levels were measured using the PAI-1 promoter-luciferase mink lung epithelial cell assay and characterized with peptide specific inhibitory antibodies. Control AEC2 produced 997 +/- 54 pg active TGF-beta x 10(6) cells-1.24h-1 (mean +/- SD), of which > 70% was TGF-beta 3, while cultured macrophages produced 58 +/- 17 pg active TGF-beta x 10(6) macrophages-1.24 h-1, > 80% of which was TGF-beta 1. During hyperoxia and recovery, active TGF-beta 3 production by AEC2 decreased by 75%, with a nadir at 24 h recovery (P < 0.005). In contrast, TGF-beta peptide activity increased from undetectable levels in lung lavage from control rats to a peak of 1,470 +/- 743 pg/rat after 48 h oxygen exposure and 24 h recovery, while lavaged macrophage TGF-beta production in culture also increased threefold to a peak of 150 +/- 5 pg. 10(6) cells-1. 24 h-1 after 48 h oxygen exposure (P < 0.005). The nadir of active TGF-beta 3 production by AEC2 coincided with the peak of the AEC2 proliferative phase of repair as determined by BrdU incorporation and FACS analysis of freshly isolated AEC2. We conclude that active TGF-beta 3 production by AEC2 is dynamically downregulated during the proliferative phase of recovery from acute hyperoxic injury in rat. We speculate that decreased autocrine negative regulation of AEC2 proliferation by TGF-beta 3 may facilitate AEC2 proliferation during recovery from acute hyperoxic injury.

Acute Disease↗

PubMed1996

Conduction aphasia in multiple sclerosis: a case report with MRI findings.

Aphasia is an uncommon manifestation of MS, which is somewhat surprising because various disconnection syndromes, such as conduction aphasia, would be expected to occur with some regularity in this white matter disease. We present a case study of an MS patient with conduction aphasia associated with a large white matter lesion underlying the left supramarginal gyrus.

Adult↗

PubMed1996

Determination of the pKa and pH-solubility behavior of an ionizable cyclic carbamate, (S)-6-chloro-4-(cyclopropylethynyl)-1,4-dihydro-4- (trifluoromethyl)-2H-3,1-benzoxazin-2-one (DMP 266).

The solubility of a nonnucleoside reverse transcriptase inhibitor, (S)-6-chloro-4-(cyclopropylethynyl)-1,4-dihydro-4-(trifluoromethyl )- 2H-3,1-benzoxazin-2-one (DMP 266), was investigated as a function of pH. A dramatic increase in the aqueous solubility was observed at pH > or = 10, which was consistent with going from a neutral to a charged species. The ionization of the proton positioned on the carbamate functionality was confirmed spectrophotometrically (pKa = 10.1). The spectrophotometric result was in excellent agreement with that obtained from the solubility studies (pKa = 10.2). The ionization behavior of DMP 266 represents a unique case in which the pKa for a carbamate functional group is quite low. The anomalous pKa value may be attributed to stabilization of the negatively charged species through inductive effects, which originate from the surrounding substituents and delocalization of the negative charge via resonance effects.

Alkynes↗

PubMed1996

Future directions in prostate cancer treatment: an oncologist's perspective.

Prostate cancer has become one of the most important national health problems, as its incidence increases yearly. Conventionally, single-modality local therapy has been the standard of care for clinically localized stage disease and systemic therapy, in the form of primary or combined androgen deprivation, is reserved for advanced, usually metastatic, prostate cancer. Despite improvements in local therapy, a significant number of patients with clinically localized prostate cancer will suffer a systemic relapse after potentially curative local therapy and, despite 50 years of experience in hormone therapy, significant survival prolongation for patients with metastatic prostate cancer remains a challenge. This paper explores potential future systemic therapy strategies in the treatment of prostate cancer. Specifically, the role of adjuvant systemic therapy as part of a multimodality treatment approach for localized prostate cancer and alternative applications of hormone and chemohormone therapies for patients with metastatic disease are discussed.

Antineoplastic Agents, Hormonal↗