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Biomedical subjects

M Hussain

Publications and source records attributed to M Hussain.

At least 55 records · Page 3Linked to original sources
PubMed2001

Combination paclitaxel, carboplatin, and gemcitabine is an active treatment for advanced urothelial cancer.

PURPOSE: To determine the efficacy and toxicity of the drug combination of carboplatin, paclitaxel, and gemcitabine in patients with advanced urothelial carcinoma. PATIENTS AND METHODS: Patients eligible included those with advanced urothelial malignancy of any histology, no previous chemotherapy for metastatic disease, Southwest Oncology Group performance status of 2 or less, serum creatinine levels of 2 mg/dL or less, and adequate bone marrow and hepatic function. Treatment consisted of paclitaxel 200 mg/m2, carboplatin (target area under the curve = 5) on day 1, and gemcitabine 800 mg/m2 on days 1 and 8, repeated every 21 days. RESULTS: Forty-nine patients (44 men and five women) were enrolled; the patients' median age was 63 years, and their median creatinine clearance was 78 mL/min (range, 26 to 165 mL/min). Forty-three patients had transitional cell carcinoma, and six had squamous cell carcinoma or mixed histology. Ten patients had metastases to lymph nodes only, six had locally advanced disease, four had locally recurrent disease, 24 patients had visceral metastases, and five had soft tissue metastases. Twenty-one patients had disease in one site, 16 in two sites, and 12 in three sites. A total of 272 cycles were administered (median, six cycles; range, 1 to 15 cycles). Major toxicities were grade 3 and 4 neutropenia in 17 and 19 patients, respectively; grade 3 and 4 thrombocytopenia in 15 and six patients, respectively; grade 3 and 4 anemia in 10 and two patients, respectively; grade 3 neuropathy in four patients; and diarrhea in two patients. The incidence of febrile neutropenia was 1.4%; no patients died of drug toxicity. Forty-seven of the 49 patients were assessable for response. Fifteen (32%) patients experienced a complete response, and 17 (36%) patients experienced a partial response (32 of 47 patients, 68%; 95% confidence interval, 56.27 to 82.86). Responses were seen in all sites, including 15 (68%) of 22 patients with visceral metastases. The median survival was 14.7 months, with a 1-year survival of 59%. CONCLUSION: Combination paclitaxel, carboplatin, and gemcitabine is active; an encouraging number of patients with advanced urothelial carcinoma treated with this regimen experienced complete remission.

Adult↗
PubMed2001

An antigen capture assay for the measurement of serum clusterin concentrations.

We have developed and validated a robust antigen capture assay for the measurement of serum clusterin. Increased clusterin expression, and alterations in serum clusterin levels have been associated with a number of disease states. In particular, clusterin has been shown to be associated with tissue regression and apoptosis in the rat ventral prostate in response to androgen ablation or administration of anti-androgens. The object of this study was to determine if changes in human serum clusterin can be used as a diagnostic or prognostic marker to monitor the response to hormonal therapy in patients with prostate cancer, and to determine if clusterin concentrations increase with the progression towards androgen independence. The antigen capture assay was used for an extensive analysis of human serum clusterin concentration in fasting males, and to determine if there is any relationship between clusterin and age or cholesterol levels. The average clusterin level in serum is 101+/-42 microg/ml (n=96). There is no correlation to age or serum cholesterol levels. Analysis of serum clusterin levels in patients with newly diagnosed prostate cancer (n=5), hormone responsive tumors (n=5), and hormone refractory disease (n=5), demonstrates that no significant changes in serum clusterin levels accompany the progression of prostatic disease, or response to hormone therapy.

Antigens↗
PubMed2001

Neoadjuvant estramustine and etoposide followed by concurrent estramustine and definitive radiotherapy for locally advanced prostate cancer: feasibility and preliminary results.

PURPOSE: Current therapy for locally advanced prostate cancer is suboptimal. A treatment regimen was designed to improve systemic control by neoadjuvant targeting of hormone-sensitive and -insensitive micrometastatic disease and to improve local control by escalating the biologic effective dose to the prostate using estramustine (EMP) concurrently with radiotherapy. PATIENTS AND METHODS: Eighteen patients with locally advanced prostate cancer (Stages T3/T4 or T1c/T2b/T2c with a Gleason score of > or =7 and a serum PSA >15 ng/ml) were entered onto this trial. Therapy consisted of two 21-day cycles of oral estramustine (10 mg/kg/day) in three divided doses and oral etoposide (50 mg/m(2)/day, in two divided doses), followed by concurrent estramustine (10 mg/kg/day, PO) and three-dimensional conformal radiotherapy. RESULTS: Two patients required discontinuation of chemotherapy due to development of Grade 3 and 4 toxicity. All others completed both components of therapy per protocol guidelines. Minor toxicities included alopecia (100% of patients), anemia (69%), leukopenia (37%), thrombocytopenia (19%), and nausea (6%) but did not require dose modifications. There were no fatalities. Actuarial 3-year overall survival and disease-free survival (DFS) were 88% and 73%, respectively. Local control rate, assessed by repeated prostate biopsies at 18 months post completion of therapy, was 71%. CONCLUSION: The described regimen is well tolerated, and preliminary efficacy data are encouraging. The underlying concepts of early targeting of both hormone-sensitive and -insensitive micrometastatic clones, in combination with aggressive local therapy, warrant further investigation.

Aged↗
PubMed2001

The cellular delivery of antisense oligonucleotides and ribozymes.

The design and development of antisense oligonucleotides and ribozymes for the treatment of diseases arising from genetic abnormalities has become a real possibility over the past few years. Improvements in oligonucleotide chemistry have led to the synthesis of nucleic acids that are relatively stable in the biological milieu. However, advances in cellular targeting and intracellular delivery will probably lead to more widespread clinical applications. This review looks at recent advances in the in vitro and in vivo delivery of antisense oligodeoxynucleotides and ribozymes.

Journal Article↗
PubMed2001

Teichoic acid enhances adhesion of Staphylococcus epidermidis to immobilized fibronectin.

Adhesion is a prerequisite for coagulase-negative staphylococci to cause invasive disease and may be mediated by adhesive host molecules adsorbed on implanted polymers. In this study, we can confirm previous observations demonstrating binding of Staphylococcus epidermidis to fibronectin (FN) adsorbed polymer surfaces. So far, the nature of FN-recognizing adhesin(s) in S. epidermidis remains elusive. Since teichoic acids (TA) have been shown to exert binding functions for extracellular matrix molecules in several Gram-positive species, we have purified wall TA of S. epidermidis laboratory strains KH11 and RP62A, as well as clinical isolate AB9. Using a polymethylmethacrylate (PMMA) coverslip adhesion assay, a microtitre plate assay and a particle agglutination assay, we found that purified TA significantly enhanced adhesion of S. epidermidis KH11 and RP62A to FN coated surfaces. Enhanced adhesion was dose-dependent and saturable. Preincubation, either of microorganisms or of FN coated surfaces, with TA promoted adhesion, while adhesion to TA-adsorbed PMMA was comparably low. This observation may suggest a potential role of cell wall carbohydrates as bridging molecules between microorganisms and immobilized FN in early steps of S. epidermidis pathogenesis.

Bacterial Adhesion↗
PubMed2001

Effects of the PKA inhibitor H-89 on excitation-contraction coupling in skinned and intact skeletal muscle fibres.

This study investigated the effects of the protein kinase A (PKA) inhibitor, H-89, in mechanically-skinned muscle fibres and intact muscle fibres, in order to determine whether PKA phosphorylation is essential for normal excitation-contraction (E-C) coupling. In skinned EDL fibres of the rat, force responses to depolarization (by ion substitution) were inhibited only slightly by 10 microM H-89, a concentration more than sufficient to fully inhibit PKA. Staurosporine (1 microM), a potent non-specific kinase inhibitor, also had little if any effect on depolarization-induced responses. At 1-2 microM, H-89 significantly slowed the repriming rate in rat skinned fibres, most likely due to it deleteriously affecting the T-system potential. With 100 microM H-89, the force response to depolarization by ion substitution was completely abolished. This inhibitory effect was reversed by washout of H-89 and was not due to block of the Ca2+ release channel in the sarcoplasmic reticulum (SR). In intact single fibres of the flexor digitorum longus (FDB) muscle of the mouse, 1-3 microM H-89 had no noticeable effect on action-potential-mediated Ca2+ transients. Higher concentrations (4-10 microM) caused Ca2+ transient failure in fibres stimulated at 20 Hz in a manner indicative of action-potential failure. At 10-100 microM, H-89 also inhibited net Ca2+ uptake by the SR and affected the Ca2+-sensitivity of the contractile apparatus in rat skinned fibres. All such effects were proportionately greater in toad muscle fibres. These results do not support the hypothesis that phosphorylation is essential for the Ca2+ release channel to open in response to voltage-sensor activation in skeletal muscle fibres.

Animals↗
PubMed2001

Hepatitis B infection in patients with acute liver failure in the United States.

Occult hepatitis B virus (HBV) infection has been reported in 30% to 50% of patients with acute liver failure (ALF) in small case series. The aim of this study was to determine the prevalence of occult HBV infection in a large series of ALF patients in the United States and the prevalence of precore and core promoter variants in patients with ALF caused by hepatitis B. Sera from patients in the US ALF study and liver, when available, were tested using nested polymerase chain reaction (PCR) with primers in the HBV S and precore regions. PCR-positive samples were sequenced. Sera and/or liver from 139 patients (39 males, 100 females; mean age, 42 years) enrolled between January 1998 and December 1999 were studied. Twelve patients were diagnosed with hepatitis B, 1 with hepatitis B+C+D coinfection, and 22 had indeterminate etiology. HBV DNA was detected in the sera of 9 (6%) patients; all 9 had ALF caused by hepatitis B. HBV genotypes A, B, C, and D were present in 4, 3, 1, and 1 patients, respectively. Seven of these 9 patients had precore and/or core promoter variants. Liver from 19 patients were examined. HBV DNA was detected in the liver of 3 patients with ALF caused by hepatitis B, but in none of the remaining 16 patients with non-B ALF. Contrary to earlier reports, occult HBV infection was not present in this large series of ALF patients in the United States. HBV precore and/or core promoter variants were common among US patients with ALF caused by hepatitis B.

Acute Disease↗
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↗
PubMed2001

Daphwazirin, biscoumarin glycopyranoside from Daphne oleoides.

Daphwazirin, a new biscoumarin glycoside (1), along with four known compounds (2), (3), (4) and (5) has been isolated from the roots of Daphne oleoides. Its chemical structure is established as 7-hydroxy-8-[2-oxo-2H-1-benzopyran-7'-(O-alpha-L-rhamnosyl)-6'-yl]-2H-1-benzopyran-2-one through spectroscopic techniques and chemical analysis.

Chromatography↗
PubMed2001

Analogs of Eap protein are conserved and prevalent in clinical Staphylococcus aureus isolates.

Map and Eap are secreted Staphylococcus aureus proteins that interact with various extracellular matrix molecules. PCR analysis using map primers yielded positive reactions in 97.9% of S. aureus isolates but not in Staphylococcus epidermidis isolates. Cloning and sequencing of the conferring genes revealed a high degree of overall homology combined with size variability of the gene product due to various repeat numbers and early translation termination in a poly(A) region. Thus, Map and Eap may provide a potential novel tool for S. aureus identification and typing.

Amino Acid Sequence↗
PubMed2001

Identification and characterization of a novel 38.5-kilodalton cell surface protein of Staphylococcus aureus with extended-spectrum binding activity for extracellular matrix and plasma proteins.

The ability to attach to host ligands is a well-established pathogenic factor in invasive Staphylococcus aureus disease. In addition to the family of adhesive proteins bound to the cell wall via the sortase A (srtA) mechanism, secreted proteins such as the fibrinogen-binding protein Efb, the extracellular adhesion protein Eap, or coagulase have been found to interact with various extracellular host molecules. Here we describe a novel protein, the extracellular matrix protein-binding protein (Emp) initially identified in Western ligand blots as a 40-kDa protein due to its broad-spectrum recognition of fibronectin, fibrinogen, collagen, and vitronectin. Emp is expressed in the stationary growth phase and is closely associated with the cell surface and yet is extractable by sodium dodecyl sulfate. The conferring gene emp (1,023 nucleotides) encodes a signal peptide of 26 amino acids and a mature protein of a calculated molecular mass of 35.5 kDa. Using PCR, emp was demonstrated in all 240 S. aureus isolates of a defined clinical strain collection as well as in 6 S. aureus laboratory strains, whereas it is lacking in all 10 S. epidermidis strains tested. Construction of an allelic replacement mutant (mEmp50) revealed the absence of Emp in mEmp50, a significantly decreased adhesion of mEmp50 to immobilized fibronectin and fibrinogen, and restoration of these characteristics upon complementation of mEmp50. Emp expression was also demonstrable upon heterologous complementation of S. carnosus. rEmp expressed in Escherichia coli interacted with fibronectin, fibrinogen, and vitronectin in surface plasmon resonance experiments at a K(d) of 21 nM, 91 nM, and 122 pM, respectively. In conclusion, the biologic characterization of Emp suggests that it is a member of the group of secreted S. aureus molecules that interact with an extended spectrum of host ligands and thereby contribute to S. aureus pathogenicity.

Adhesins, Bacterial↗
PubMed2001

Discitis in young children.

Discitis is uncommon in children and presents in different ways at different ages. It is most difficult to diagnose in the uncommunicative toddler of one to three years of age. We present 11 consecutive cases. The non-specific clinical features included refusal to walk (63%), back pain (27%), inability to flex the lower back (50%) and a loss of lumbar lordosis (40%). Laboratory tests were unhelpful and cultures of blood and disc tissue were negative. MRI reduces the diagnostic delay and may help to avoid the requirement for a biopsy. In 75% of cases it demonstrated a paravertebral inflammatory mass, which helped to determine the duration of the oral therapy given after initial intravenous antibiotics. At a mean follow-up of 21 months (10 to 40), all the spines were mobile and the patients free from pain. Radiological fusion occurred in 20% and was predictable after two years. At follow-up, MRI showed variable appearances: changes in the vertebral body usually resolved at 24 months and recovery of the disc was seen after 34 months.

Anti-Bacterial Agents↗
PubMed2001

Her-2/neu overexpression in muscle-invasive urothelial carcinoma of the bladder: prognostic significance and comparative analysis in primary and metastatic tumors.

PURPOSE: The prognostic significance of Her-2/neu overexpression in muscle-invasive urothelial carcinoma of the bladder is largely unknown. Accurate determination of Her-2/neu overexpression may have therapeutic importance. EXPERIMENTAL DESIGN: Eighty consecutive cases of muscle-invasive urothelial carcinoma of the bladder treated by radical cystectomy with available follow-up were analyzed. In each case, one representative section was stained with anti-Her-2/neu. Staining was graded as 1 = faint/equivocal, 2 = moderate, and 3 = strong and was considered positive if > or =2. In those cases with a metastasis, the stain was also performed in the metastatic tumor. Results were correlated with survival. RESULTS: Twenty-two (28%) cases were considered Her-2/neu-positive in the primary tumor, and 17 of 32 (53%) were considered Her-2/neu-positive in the lymph node metastasis. Median survival for Her-2/neu-positive primary tumors was 33 months, compared with 50 months for Her-2/neu-negative cases (P = 0.46). Similarly, Her-2/neu overexpression in the lymph node metastasis did not predict survival. Sixty metastatic urothelial carcinomas were further studied by comparing Her-2/neu expression in the primary tumor with that of the lymph node and/or distant metastasis. Forty-five percent of Her-2/neu-negative primary tumors had a Her-2/neu-positive lymph node metastasis, whereas only one case (8%) of Her-2/neu-positive primary tumors was Her-2/neu-negative in the lymph node metastasis (P = 0.009). Similarly, 67% of Her-2/neu-negative primary tumors had a Her-2/neu-positive distant metastasis, whereas no Her-2/neu-positive primary tumor was negative in the metastasis (P = 0.429). CONCLUSIONS: Her-2/neu overexpression in primary or metastatic tumor did not predict survival in this cohort of muscle-invasive tumors. Overexpression in the primary tumors consistently predicts overexpression in a distant or regional metastasis. However, some Her-2/neu-negative primary tumors may show overexpression in their corresponding metastasis. Her-2/neu analysis in a metastasis may be necessary to accurately determine Her-2/neu status in metastatic bladder urothelial carcinoma.

Humans↗
PubMed2001

Survey of knowledge about tuberculosis amongst family physicians.

OBJECTIVE: To investigate the knowledge, attitudes and practices pertaining to tuberculosis (TB) amongst family physicians. METHOD: A questionnaire-based study in which 150 family physicians were interviewed. RESULTS: Of the family physicians 21.3% considered that TB is not a serious problem; 29% did not advise BCG vaccination as they considered that BCG vaccination has adverse side effects and limited usefulness. Only 38% depended on sputum analysis for diagnosis and 39% were prescribing four drug regimen for newly diagnosed TB patients. Majority of family physicians were prescribing the drugs that are classified currently as non-recommendable. Only 7.3% were able to write down the correct contents and quantity of tablets of what they were prescribing. CONCLUSION: There are many misunderstandings about the transmission of tuberculosis and BCG vaccinations. Method of diagnosis, treatment and monitoring of treatment by and large is not satisfactory.

BCG Vaccine↗