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Biomedical subjects

M Green

Publications and source records attributed to M Green.

At least 469 records · Page 26Linked to original sources

Recovery of vancomycin-resistant gram-positive cocci from children.

A cross-sectional survey of vancomycin-resistant gram-positive cocci (VRGPC) in the feces of children was initiated after several bacteremic infections with these organisms occurred at our hospital. A selective medium consisting of colistin-nalidixic acid agar, 5% sheep blood, vancomycin (5 mg/liter), and amphotericin B (8 mg/liter) was developed to isolate VRGPC. A single stool specimen submitted to the clinical microbiology laboratory from each of 48 patients was inoculated onto the medium. Plates were incubated at 35 degrees C with 5% carbon dioxide and examined at 24, 48, and 72 h. Susceptibilities were determined by broth microdilution. A total of 14 isolates from 11 of 48 (22%) children were recovered. The density of growth ranged from a single colony to 2+. The VRGPC were identified as Leuconostoc lactis (n = 2), Lactobacillus confusus (n = 4), Enterococcus species (n = 5), and Lactococcus lactis (n = 3). One strain of Lactobacillus confusus was recovered from both the stool and the blood of one of these patients. The MICs of vancomycin were 4 micrograms/ml for one of the isolates, 8 micrograms/ml for four of the isolates, and more than 16 micrograms/ml for the remaining eight isolates. All isolates were susceptible to both penicillin and ampicillin. Only 1 of the 11 children had received prior treatment with vancomycin. We conclude that low concentrations of VRGPC may be common in the gastrointestinal tracts of children.

Child↗

Chemical synthesis of human papillomavirus type 16 E7 oncoprotein: autonomous protein domains for induction of cellular DNA synthesis and for trans activation.

The human papillomavirus type 16 E7 protein belongs to a family of nuclear oncoproteins that share amino acid sequences and functional homology. To localize biochemical activities associated with E7, we chemically synthesized the full-length 98-amino-acid polypeptide and several deletion mutant peptides. We show that the E7 polypeptide is biologically active and possesses at least two functional domains; the first induces cellular DNA synthesis in quiescent rodent cells, and the second trans activates the adenovirus E1A-inducible early E2 promoter and binds zinc. Further, each domain is autonomous and can function on separate peptides. DNA synthesis induction activity maps within the N-terminal portion of the molecule, which contains sequences related to adenovirus E1A conserved domains 1 and 2 required for cell transformation and binding of the retinoblastoma gene product. trans-Activation and Zn-binding activities map within the C-terminal portion of the molecule, a region which contains Cys-X-X-Cys motifs. trans Activation does not require protein synthesis, implying a mechanism that involves interaction with a preexisting cellular factor(s). E7 trans activates the adenovirus E2 promoter but not other E1A-inducible viral promoters, suggesting the possibility that E7 trans activation involves interaction, directly or indirectly, with cellular transcription factor E2F.

Adenoviruses, Human↗

Respiratory muscle function in cystic fibrosis.

Maximal static expiratory and inspiratory mouth pressures (PEmax and PImax) and quadriceps femoris muscle strength were measured in 25 patients aged 16-28 years with cystic fibrosis (mean FEV1 46% predicted). Mean (SD) PEmax was 64% (18%) predicted (below 75% predicted in 16 of the 25 patients), and PImax was 64% (24%) predicted (below 75% predicted in 14 patients). Quadriceps muscle strength was 68% (20%) predicted (below 75% predicted in 17 patients). The relatively small reduction in respiratory muscle strength in these patients was unlikely to have contributed appreciably to their respiratory problems.

Adolescent↗

Unsuspected myasthenia gravis presenting as respiratory failure.

A patient developed respiratory failure after surgical removal of a recurrent thymoma, which necessitated removal of part of the diaphragm. The respiratory failure was due to previously undiagnosed myasthenia gravis, which had selectively affected the respiratory muscles.

Azathioprine↗

Tracheobronchial clearance in patients with bilateral diaphragmatic weakness.

Tracheobronchial clearance was measured in seven patients with bilateral diaphragmatic weakness using a noninvasive objective radioaerosol technique. The data were compared with those from seven healthy nonsmoking control subjects matched for physical characteristics and studied under the same experimental conditions; the control subjects were drawn from a data bank of healthy subjects and were matched to the patients for age, sex, and the initial distribution of their radioaerosol deposition. Pulmonary function indices (FEV1, FVC, PEFR, and MMFR25-75) for the patients were all significantly (p less than 0.01) reduced compared with those for the control subjects. The initial topographic distribution of the radioaerosol within the lungs of the patients and control groups was similar: alveolar deposition [mean (SD)] was 36.4 (6.7) versus 41.0 (4.0)%, and penetration index was 0.56 (0.08) versus 0.56 (0.03), respectively. Tracheobronchial clearance of deposited radioaerosol over a 6-h observation period after inhalation showed a marked reduction (p less than 0.02) in the patients: area under the clearance curve (between zero and 6 h) was 262 (80)% h for the patients and 142 (41)% h for the healthy control subjects. These data suggest that in patients with bilateral diaphragmatic weakness, mucociliary clearance is depressed, or that reduced mechanical movement of the lungs can itself impair clearance of secretions from the lungs. Impaired clearance from either cause may contribute to an increased incidence of chest infections in severe respiratory muscle weakness.

Adult↗

Intraperitoneal carboplatin: favorable results in women with minimal residual ovarian cancer after cisplatin therapy.

From August 1985 to November 1989 we conducted a trial of intraperitoneal (IP) carboplatin including a dose-escalation design in 25 women with advanced gynecologic malignancies. All had extensive prior therapy with cisplatin (median cumulative dose, 525 mg/m2). Carboplatin was administered IP in 2 L of 1.5% dextrose with a 4-hour dwell time every 4 weeks for six cycles at a starting dose of 200 mg/m2. Patients with reduced creatinine clearance (30 to 60 cc/min) were escalated more slowly than those with high (greater than 60 cc/min) clearance. Thrombocytopenia was dose-limiting and often more severe in patients with compromised renal function; there was no local drug toxicity. The median time of follow-up is 25 months. Complete responses (CRs) were documented in six of 23 assessable patients (26%) by repeat laparotomy, and an additional 11 patients (48%) had no disease evident by noninvasive restaging. Five of the CRs and six of the patients with no clinically evident disease have relapsed from 3 to 40 months after therapy. Six patients (26%) are alive and free of disease 8 to 47 (median, 20) months after therapy. IP carboplatin is effective against relapsed ovarian cancer, even after prior cisplatin therapy.

Adenocarcinoma↗

Public health implications of the microbial pesticide Bacillus thuringiensis: an epidemiological study, Oregon, 1985-86.

Bacillus thuringiensis var. kurstaki (B.t.-k) is a microbial pesticide which has been widely used for over 30 years. Its safety for a human population living in sprayed areas has never been tested. Surveillance for human infections caused by B.t.-k among Lane County, Oregon residents was conducted during two seasons of aerial B.t.-k spraying for gypsy moth control. Bacillus isolates from cultures obtained for routine clinical purposes were tested for presence of Bacillus thuringiensis (B.t.). Detailed clinical information was obtained for all B.t.-positive patients. About 80,000 people lived in the first year's spray area, and 40,000 in the second year's area. A total of 55 B.t.-positive cultures were identified. The cultures had been taken from 18 different body sites or fluids. Fifty-two (95 percent) of the B.t. isolates were assessed to be probable contaminants and not the cause of clinical illness. For three patients, B.t. could neither be ruled in nor out as a pathogen. Each of these three B.t.-positive patients had preexisting medical problems. The level of risk for B.t.-k and other existing or future microbial pesticides in immunocompromised hosts deserves further study.

Abscess↗

Metabolism of low-dose paracetamol in patients with chronic neurological disease.

1. Low dose (500 mg) paracetamol (acetaminophen) was administered to patients with Parkinson's disease, motor neurone disease and to age-matched controls. 2. At this low dose level the controls excreted proportionately more sulphate and less glucuronide conjugate than has been reported for administration of 1000 mg of paracetamol. 3. Both groups of patients with chronic neurological disease excreted decreased amounts of paracetamol sulphate (control mean 11.2 +/- 5.4% dose; Parkinson's disease 3.9 +/- 3.7%; motor neurone disease, 5.0 +/ 4.1%). 4. The mean ratio of excretion of paracetamol sulphate/paracetamol glucuronide was 5.6 +/- 11.7 in controls, but 1.1 +/- 1.7 and 1.2 +/- 1.7 in Parkinson's disease and motor neurone disease respectively. These differences are statistically significant (p less than 0.001).

Acetaminophen↗

Risk prediction in medicine and surgery: ethical and practical considerations.

Risk prediction is a subject of increasing clinical interest, and publications in this area are likely to have an important influence on patient care in the near future. A multiplicity of risk prediction systems, many of them computer-based, will raise a number of ethical and practical questions. These questions need to be addressed by the originators of systems, the editors of journals, practising clinicians, and the lay public.

Biomedical Research↗

Seasonality and long-term trends of pediculosis capitis and pubis in a young adult population.

Little is known about seasonality and long-term trends in the incidence of pediculoses. Such information would help both public health workers and clinicians in the prevention and management of the problem. In the Israel Defence Forces the pediculoses are individually notifiable, and this provides a unique database for the study of this subject. The incidence of head louse infestation increased from 5.2 per 1000 in 1977 to 18.1 per 1000 in 1979, and then declined to 3.6 per 1000 in 1987. The incidence was higher in the warmer months. Pubic louse infestation increased from 7 per 1000 in 1977 to 14.9 per 1000 in 1983, and then declined to 4.6 per 1000 in 1987. The incidence was higher in the cooler months. Possible causes of the seasonality and long-term trends are discussed.

Adult↗

In vitro trans-activation by chemically synthesized adenovirus region 3 peptides. Reaction properties and mutational analysis.

The adenovirus E1A gene encodes a protein that transcriptionally activates viral early genes. We have reported that a 49-amino acid chemically synthesized adenovirus type 2 E1A region 3 peptide, PD3 (residues 140-188 of the 289-amino acid protein), can stimulate transcription in vitro from the adenovirus major late promoter. Here we describe reaction properties of E1A trans-activation in vitro with the major late promoter and the early gene 3 promoter and the structural requirements for activity. Stimulation of transcription by PD3 is highest with low levels of DNA template and nuclear extract, and the presence of PD3 eliminates the need to preincubate template with nuclear extract to achieve optimal transcription. These findings suggest that PD3 facilitates a rate-limiting step in the formation of a promoter complex. Analysis of deletion and cysteine substitution mutant PD3 peptides indicates that the C-terminal 70% of the peptide is sufficient for trans-activation in vitro and supports the hypothesis that PD3 contains two functional subregions. The function of one region (residues 140 to about 152) can be overridden under conditions used for in vitro transcription. The second region (residues 153-188) is essential and may function both as a promoter-binding region and as an activating region in vitro.

Adenovirus Early Proteins↗

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Education, Nursing↗

Mutational analysis of HIV-1 Tat minimal domain peptides: identification of trans-dominant mutants that suppress HIV-LTR-driven gene expression.

The HIV-1 Tat protein is a potent trans-activator essential for virus replication. We reported previously that HIV-1 Tat peptides containing residues 37-48 (mainly region II), a possible activating region, and residues 49-57 (region III), a nuclear targeting and putative nucleic acid binding region, possess minimal but distinct trans-activator activity. The presence of residues 58-72 (region IV) greatly enhances trans-activation. We postulate that Tat mutant peptides with an inactive region II and a functional region III can behave as dominant negative mutants. We synthesized minimal domain peptides containing single amino substitutions for amino acid residues within region II that are conserved among different HIV isolates. We identify four amino acid residues whose substitution within Tat minimal domain peptides leads to defects in transactivation. Some of these mutants are trans-dominant in several peptide backbones, since they strongly inhibit trans-activation by wild-type Tat protein added to cells or expressed from microinjected plasmid. Significantly, trans-activation of integrated HIV-LTRCAT is blocked by some trans-dominant mutant peptides. These results suggest an attractive approach for the development of an AIDS therapy.

Amino Acid Sequence↗

Effects of bacterially synthesized recombinant human granulocyte-macrophage colony-stimulating factor in patients with advanced malignancy.

STUDY OBJECTIVE: To define the clinical and hematologic effects of subcutaneously administered bacterially synthesized recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF). DESIGN: Single arm nonrandomized dose escalation study. PATIENTS: Twenty-one patients with advanced malignancy who were not receiving concurrent myelosuppressive therapy. INTERVENTIONS: Subcutaneous administration of rhGM-CSF by once-daily injection to groups of two to four patients at doses of 0.3 to 30 micrograms/kg body weight.d for 10 consecutive days. Some patients received a second 10-day period of daily rhGM-CSF treatment after a 10-day nontreatment interval followed by alternate-day treatment. Clinical status and hematologic values were monitored frequently. MEASUREMENTS AND MAIN RESULTS: All doses of rhGM-CSF caused an immediate transient fall of 84% to 99% in circulating neutrophils, eosinophils, and monocytes. Continued daily dosing caused a leukocytosis of up to 10-fold with increases in numbers of circulating neutrophils, eosinophils, monocytes, and lymphocytes. There appeared to be a plateau in the increase in neutrophils in the dose range 3 to 15 micrograms/kg.d. Marrow aspirates showed increased proportions of promyelocytes and myelocytes. Alternate-day injection of 15 micrograms/kg maintained a leukocytosis. At doses up to 15 micrograms/kg.d, rhGM-CSF was well tolerated but adverse effects included bone pains, myalgias, rashes, and liver dysfunction. At doses exceeding 15 micrograms/kg.d, pericarditis was a dose-limiting toxicity. Idiopathic thrombocytopenic purpura was reactivated by rhGM-CSF in one patient. CONCLUSIONS: Bacterially synthesized rhGM-CSF induces a leukocytosis in the dose range of 3 to 15 micrograms/kg.d. These doses are appropriate for phase II studies.

Adult↗

Neuroleptic malignant syndrome. Review of response to therapy.

The purpose of this study was to evaluate options available for the treatment of neuroleptic malignant syndrome. We conducted a computer search of English-language literature using a Medline database and review of bibliographies of identified articles. Sixty-four case reports containing sufficient data about patients' demographics and clinical response to therapy to allow evaluation were combined with three previously unreported cases. The mean time to clinical response was 6.8 days when supportive measures alone were used in the treatment of neuroleptic malignant syndrome. The addition of dantrolene (response time, 1.15 days) or bromocriptine (response time, 1.03 days) significantly shortened the time to clinical response. We conclude that the addition of either dantrolene or bromocriptine to conservative measures decreases the time to clinical response. A randomized trial would address potential case selection biases.

Adult↗

Phase II study of N-methylformamide, spirogermanium, and 4-demethoxydaunorubicin in the treatment of non-small cell lung cancer (EST 3583): an Eastern Cooperative Oncology Group study.

One hundred forty-four patients with non-small cell lung cancer, the majority (72%) of whom had received previous chemotherapy, were evaluable in this randomized phase II study of N-methylformamide (N-MF), spirogermanium, and 4-demethoxydaunorubicin. There were two partial responses, one each with spirogermanium and 4-demethoxydaunorubicin. There were eight life-threatening complications (mostly hematologic) and two lethal complications (N-MF, hematologic; 4-demethoxydaunorubicin, gastrointestinal). The overall survival ranged from 9 days to 533 days with a median of 17.6 weeks. The following factors were associated with poor survival: Poor initial performance status, prior weight loss, presence of liver or subcutaneous metastases.

Aged↗