Search PubMed⌕ Search

Biomedical subjects

M Brady

Publications and source records attributed to M Brady.

At least 73 records · Page 4Linked to original sources
PubMed1995

The role of paclitaxel in the management of coelomic epithelial carcinoma of the ovary: a review with emphasis on the Gynecologic Oncology Group experience.

Coelomic epithelial carcinoma of the ovary, the most common cause of death from cancer of the female genital tract in the United States, presents most commonly as advanced (stage III or IV) disease. Management consists of aggressive surgical cytoreduction followed by combination chemotherapy, until recently, a platinum compound plus an alkylating agent. The recent identification of the activity of paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) offers the potential to improve further the management of patients with advanced disease. That this agent might enhance current front-line therapy is supported by its unique mechanism of action and by the significant numbers of responses reported in patients clinically resistant to the platinum compounds: more than 20% of these patients responded to paclitaxel as salvage therapy in four different phase II trials. These observations led to a phase I Gynecologic Oncology Group trial that showed that paclitaxel 135 mg/m2 over 24 hours followed by cisplatin 75 mg/m2 could be given every 3 weeks. This group then compared six cycles of the identified regimen with six cycles of standard cisplatin/cyclophosphamide chemotherapy given every 3 weeks in a phase III trial in 388 previously untreated patients with large-volume (residual nodules > 1 cm after surgery) disease. The results show the superiority of the paclitaxel/cisplatin regimen: overall response rate 77% versus 62%, clinical complete response 54% versus 33%, frequency of achieving a grossly disease-free state at second-look laparotomy 40% versus 22%, progression-free survival 18 versus 13 months, and overall survival 38 versus 24 months. Thus, paclitaxel/cisplatin is the new standard of care for patients with advanced ovarian carcinoma. Current phase III studies explore further the role of paclitaxel in front-line therapy: the relative merits of single-agent versus combination chemotherapy, the role of interval surgical cytoreduction combined with paclitaxel/cisplatin, the value of carboplatin-based versus cisplatin-based combinations with paclitaxel, the significance of the paclitaxel infusion length (3 v 24 v 96 hours), and the value of more dose-intense combinations.

Antineoplastic Agents, Phytogenic↗
PubMed1994

Rat kidney carboxylesterase. Cloning, sequencing, cellular localization, and relationship to rat liver hydrolase.

We recently purified from rat liver microsomes a carboxylesterase, designated hydrolase B, that catalyzes the hydrolysis of para-nitrophenylacetate with low affinity (Km approximately 400 microM) and is relatively insensitive to the inhibitory effects of phenylmethylsulfonyl fluoride. A carboxylesterase with identical properties is also present in rat kidney microsomes, at levels comparable to those in liver microsomes. The kidney enzyme is immunochemically indistinguishable from hydrolase B by Western immunoblotting and Ouchterlony double diffusion analysis. This study describes the cloning and sequencing of hydrolase B. A 1809-base pair (bp) cDNA was isolated from a rat kidney cDNA library screened with antibody against hydrolase B. Screening the same cDNA library by two-step polymerase chain reaction with external and internal primers based on the sequence of the 1809-bp cDNA and a primer based on the sequence of the adjoining lambda gt11 arm yielded a 279-bp cDNA that overlapped by 179 bp with the 1809-bp-sequence. Together these two cDNAs spanned a 1909-bp sequence with an opening reading frame encoding 561 amino acids, which includes all 543 amino acid residues in the mature protein plus an 18-amino acid signal peptide at the N terminus. The mature protein encoded by this kidney cDNA matches perfectly the N-terminal amino acid sequence of purified hydrolase B for 30 amino acid residues, as determined by automated Edman degradation. The mature protein contains 5 cysteine residues, two potential N-linked glycosylation sites, and a C-terminal tetrapeptide (His-Asn-Glu-Leu) that matches the HXEL consensus sequence for retaining proteins in the lumen of the endoplasmic reticulum. Based on alignment of conserved amino acid sequences in several mammalian carboxylesterases, and based on the mechanism of catalysis of serine proteases, the catalytic triad in hydrolase B is apparently composed of the nucleophile Ser203, the basic amino acid His448, and the acidic amino acid Asp97 or Glu228. Northern blots probed with the 1809-bp cDNA identified high levels of a approximately 2-kilobase mRNA for hydrolase B in liver and kidney. Little or no mRNA for hydrolase B was detected in testis, lung, prostate, brain, and heart, which confirms the tissue distribution of hydrolase B based on catalytic activity and Western immunoblotting. Immunocytochemical studies established that hydrolase B is localized in the centrilobular region of the liver and in the proximal tubules of the kidney, where it presumably plays a role in the metabolism of xenobiotics and possibly endogenous lipids, although a precise physiological role for hydrolase B remains to be determined.

Amino Acid Sequence↗
PubMed1993

Purification and characterization of calmodulin-dependent protein kinase III from rabbit reticulocytes and rat pancreas.

Calmodulin-dependent protein kinase III (CaM kinase III) phosphorylates and thereby inactivates eukaryotic elongation factor-2 (EF-2). This enzyme, purified to homogeneity from either rabbit reticulocytes or rat pancreas, had similar properties: it migrated with an apparent M(r) of 140,000 by gel filtration, was comprised of a major polypeptide of M(r) 95,000 by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and had a high affinity for CaM (half-maximal activation < 1 nM). The M(r) 95,000 polypeptide was autophosphorylated by an intramolecular mechanism on seryl residues in the presence of Ca2+, CaM, and ATP, and phosphopeptide mapping indicated that several sites were phosphorylated. Autophosphorylation of CaM kinase III resulted in the generation of a partially Ca2+/calmodulin-independent activity. The enzyme could also be phosphorylated by the catalytic subunit of cAMP-dependent protein kinase. Amino acid sequencing of CaM kinase III indicated that it is distinct from other known proteins including the heat-shock protein hsp90, which was recently suggested to be identical to CaM kinase III (Nygärd, O., Nilsson, A., Carlberg, U., Nilsson, L., and Amons, R. (1991) J. Biol. Chem. 266, 16425-16430). Furthermore, hsp90 did not copurify with CaM kinase III, and the M(r) 95,000 protein did not cross-react with antibodies to hsp90. CaM kinase III exhibited Michaelis-Menten kinetics toward its substrates ATP and EF-2, with Km values of 15 and 2 microM, respectively. CaM kinase III was able to phosphorylate yeast EF-2 with an Km of 2 microM, but the enzyme did not significantly phosphorylate a variety of other substrates, confirming its identification as a novel protein kinase.

Amino Acid Sequence↗
PubMed1993

Giving away the grog: an ethnography of Aboriginal drinkers who quit without help.

The paper presents preliminary findings from a qualitative study of Australian Aboriginal men who have stopped drinking without the assistance of residential treatment, counselling or other programs. Main reasons advanced by interviewees for ceasing drinking were one or more of: medical condition and/or doctor's warning; family factors; trauma from accidents; conversion to Christianity. The author concludes that employment both helps and hinders abstention from drinking, and that social ties often pose major difficulties for those trying to give up drinking. The paper also discusses the importance of Aboriginal beliefs regarding personal autonomy.

Journal Article↗
PubMed1993

Time course of neuromuscular effects and pharmacokinetics of rocuronium bromide (Org 9426) during isoflurane anaesthesia in patients with and without renal failure.

We have studied the onset and duration of action and pharmacokinetics of rocuronium bromide (Org 9426) during anaesthesia with nitrous oxide, fentanyl and isoflurane after a single bolus dose of rocuronium 0.6 mg kg-1 in nine patients with chronic renal failure requiring regular haemodialysis, and in nine healthy control patients. Blood samples were collected over 390 min and concentrations of rocuronium and its putative metabolites measured using HPLC. Onset time for maximum block, duration of clinical relaxation (T1(25)) and recovery index, were 61 (SD 25.0) s and 65 (16.4) s, 55 (26.9) min and 42 (9.3) min and 28 (12.3) min and 19 (8.8) min, respectively, for patients with and without renal failure. The time for TOF ratio to return spontaneously to 0.7 was 99 (41.1) min and 73 (24.2) min, respectively, in the two groups. None of these differences was significant. The pharmacokinetic data were best described by a three-exponential equation. There were significant differences between patients with and without renal failure in the rates of clearance (2.5 (1.1) ml kg-1 min-1 and 3.7 (1.4) ml kg-1 min-1, respectively) and the mean residence times (97.1 (48.7) min and 58.3 (9.6) min) P < 0.05). The differences in other kinetic parameters were not significant. We conclude that the effects of rocuronium may be prolonged in patients with renal disease, because of a decreased clearance of the drug.

Adult↗
PubMed1993

HIV-1 isolates from children with or without AIDS have similar in vitro biologic properties.

OBJECTIVE: To compare biologic properties of HIV-1 isolates from children with and without AIDS as a measure of viral cytopathogenicity. PATIENTS AND PARTICIPANTS: Virus isolates from peripheral blood mononuclear cells of 13 perinatally infected children were compared for specific in vitro biologic properties. METHODS: Virus isolates were examined for biologic properties as measured by their ability to infect H9 cells and to induce syncytia in susceptible cells. RESULTS: Most of the pediatric HIV-1 isolates failed to infect CD4+ H9 cells and induce syncytia in susceptible cells, regardless of whether they were from children with or without AIDS. All of the isolates, however, grew well in mitogen-stimulated normal adult lymphocytes. These results are in contrast to those with HIV-1 isolates from adults, whose biologic properties were related to the stages of the disease. CONCLUSIONS: These results indicate that, unlike adult HIV-1 isolates, the biologic properties of pediatric isolates are not related to the stages of the disease. The rapid development of disease in children may therefore be due to factors other than intrinsic properties of HIV-1 strains present in children.

Acquired Immunodeficiency Syndrome↗
PubMed1993

Hypersensitivity to latex in health care workers: report of five cases.

Concern about transmission of acquired immunodeficiency syndrome and hepatitis has greatly increased the use of latex gloves. Latex allergy is a newly emerging problem with potential life-threatening sequelae among health care personnel. Patients are also at risk. We report on five cases of latex allergy in health care workers who were using latex gloves for variable lengths of time before their allergic reaction. All workers had a significant history of reactions to other allergens, including inhalants and food. Each individual had at least one systemic symptom that was directly attributed to latex exposure. Reactions to latex ranged from severe contact urticaria (all cases), bronchospasm (three cases), angioedema (two cases), and rhinorrhea (one case) to anaphylactic reactions that required immediate attention in three cases. Levels of specific IgE to latex (as measured by in vitro enzyme immunoassay) and total IgE were elevated in all five patients (total IgE > 100 kU/L). Long-term treatment included avoidance of latex, administration of antihistamines, and desensitization to other, nonlatex allergens. Health care workers should have increased awareness of latex allergy. At risk are health care workers with a history of other allergies and those with atopic dermatitis or eczema. In vitro testing may be useful, especially in persons with skin conditions such as eczema or urticaria or for persons with a history of systemic reactions to the latex allergen as reported in these five cases.

Adult↗
PubMed1992

Healthcare in Europe--Ireland. Change and tradition.

Community spirit and top-quality professionals have given Ireland a health status that belies its relative lack of wealth. But it is time to find a better management system, says Marie Brady.

Eligibility Determination↗
PubMed1992

Self-fulfilling effects of stigmatizing information on children's social interactions.

The stigmatizing effects of negative expectancies were examined in observations of interactions between children with and without a behavior problem. Ss were 68 pairs of unacquainted boys in Grades 3-6. In each dyad, a normal boy was either told that his partner had a behavior problem or given no expectancy; this expectancy manipulation was crossed with the partner's actual diagnostic status with respect to hyperactivity. The perceivers' expectancy that their partner had a behavior problem as well as the actual diagnostic status of the target adversely affected the boys' interactions. Behavioral data suggest how the expectancies were communicated to the target. The processes underlying interpersonal expectancy effects and the ways in which a childhood stigma can act as a self-fulfilling prophecy are discussed.

Attention Deficit Disorder with Hyperactivity↗
PubMed1992

Drug screening of newborns by meconium analysis: a large-scale, prospective, epidemiologic study.

A large-scale, prospective drug screening of newborns by meconium analysis was done to determine more accurately the prevalence and epidemiologic characteristics of drug use in a high-risk urban, obstetric population. Every other neonate delivered in a perinatal center from November 1988 to September 1989 was prospectively enrolled and their meconium was analyzed by radioimmunoassay for the metabolites of three commonly abused drugs--cocaine, morphine (opiates), and cannabinoid. In 3010 subjects studied, 44% were positive for cocaine, morphine, or cannabinoid; 31% were positive for cocaine, 21% for morphine, and 12% for cannabinoid. In contrast, only 335 (11%) mothers admitted to illicit drug use: 52% of their newborns had a positive urine drug screen and 88% had a positive meconium drug screen. Prevalence of drug use among the pregnant women varied per month. A profile of the pregnant addict in the population studied was noted (P less than .001): service patient, single, multigravid (greater than 3), and little or no prenatal care. The major problems associated with drug use during pregnancy were principally noted in the group that was exposed to cocaine and opiates and in the group where the mothers admitted to the use of illicit drugs. On the other hand, a large number of neonates who have been exposed to drugs in utero, particularly those whose mothers denied the use of drugs, appear normal at birth and may not be recognized. Improved detection of these newborns at risk can be achieved with a high index of suspicion and meconium drug analysis.

Cannabis↗