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Biomedical subjects

M Flaherty

Publications and source records attributed to M Flaherty.

8 recordsLinked to original sources
PubMed1989

A phase I clinical and pharmacokinetic study of carboplatin and autologous bone marrow support.

A series of 33 patients were treated with a four-day continuous infusion of carboplatin in a phase I study to determine the maximum-tolerated dose (MTD) of this agent when used with autologous bone marrow reinfusion. Doses were escalated from 375 to 2,400 mg/m2; autologous bone marrow reinfusion was added to the regimen at doses of 1,600 mg/m2 and above. The MTD was determined to be 2,000 mg/m2. Dose-limiting toxicity consisting of reversible hepatotoxicity, renal dysfunction, and moderate to severe ototoxicity was observed with a dose of 2,400 mg/m2. There were ten responses in 31 heavily pretreated patients, including six responses in 11 patients with recurrent ovarian cancer. Pharmacokinetic studies revealed a systemic clearance (Clss) of 4.5 L/m2/h. This value is consistent with clearances reported for carboplatin administered at lower doses and by different schedules. No evidence for saturation of systemic clearance at higher doses was observed. Carboplatin appears to be an active drug that can undergo considerable dose escalation when used in conjunction with autologous bone marrow support.

Adult↗
PubMed1986

Selective inhibition of collagen synthesis by the Ca2+ ionophore A23187 in cultured human fibroblasts.

The question of whether the Ca2+ ionophore A23187 affects collagen production relative to total protein synthesis or has possible effects on collagen degradation was investigated. Cultured normal human fibroblasts were incubated with radioactive proline, and the radioactivity of collagenase-sensitive and -resistant proteins was used to calculate the rates of protein production. The net production of collagen relative to total proteins was inhibited by A23187 in a dose-related manner, and 50% inhibition of basal collagen production was achieved with 0.6 microM A23187. There was a 70% decrease in the absolute rate of collagen production in the presence of 0.6 microM A23187 which represented a 4-fold greater inhibition of collagen production than of noncollagen protein production. The major mechanism for the decreased net production of collagen was decreased synthesis, rather than increased degradation. Ca2+ mobilization induced by cholecystokinin octapeptide was also associated with selective inhibition of collagen production in normal human fibroblasts. These studies establish that the Ca2+ ionophore A23187 induces a selective decrease in collagen polypeptide synthesis by normal human fibroblasts and suggest a modulatory role of Ca2+ on collagen metabolism.

Calcimycin↗
PubMed1986

Preschool children's conceptions of health and health behaviors.

Conceptions of health and health related behaviors of 41 four and five year olds were explored, using a picture-interview guide. Areas of interest included feeling tone associated with health, identification of children who are healthy, health promotion behaviors, behaviors deleterious to health, and individuals who help children stay healthy. Subjects' responses to selected questions were scored; choices from groups of pictures concerned with health promotion behaviors and persons who help in maintaining health were ranked, depending on order of selection. Most subjects were able to make the correct association between feeling tone and health status, and determine health status of depicted children. Health promotion behaviors selected--in descending order of mean ranking--were eating, visiting the doctor, brushing teeth, sleeping, running, and washing hands. Most subjects could correctly identify behaviors hazardous to health. Chi-square revealed no significant differences in scores or rankings by age or sex. Subjects in the lowest of the three family income groups tended to have lower scores.

Age Factors↗
PubMed1977

A comparative study of long-stay psychiatric patients discharged to boarding houses and satellite houses.

A comparative psychosocial study of two groups of long-stay psychiatric patients discharged from Callan Park Hospital to boarding houses and satellite houses in the Callan Park Hospital region is reported. It was concluded that the social and vocational functioning of both groups was at a low level but that satellite house residents had more spare money and described a less institutionalized and a more homely environment in satellite houses.

Attitude to Health↗
PubMed1977

Overview of four clinical studies of chemotherapy for stage III and IV non-Hodgkin's lymphomas by the Cancer and Leukemia Group B.

This paper presents an overview of four Cancer and Leukemia Group B studies in 1266 patients with stage III-IV non-Hodgkin's lymphoma. The cases were analyzed across protocols; the major prognostic determinants were prior chemotherapy, age, and histology. The four studies proved that cyclophosphamide maintenance was superior to no maintenance even after prolonged intensive induction chemotherapy. Furthermore, the reinforcement program of monthly pulse doses of vincristine and prednisone, whose value was established in the treatment of acute leukemia, led to highly significant improvement in remission duration and survival. Other facets of the chemotherapy programs are still being subjected to analysis, but this report sets out some preliminary conclusions.

Adult↗
PubMedDate not supplied

Different mechanisms decrease hepatic collagen and albumin production in fasted rats.

Weight loss is correlated with a specific decrease in collagen synthesis in extrahepatic tissues, mainly through modulation of mRNA levels. Here, we investigated the response to weight loss in the rat liver. Male rats were either fed ad libitum or fasted for 92 hr; fasted animals lost approximately 20% of their initial body weight. Following i.p. injection of [5-3H]proline, hepatic collagen was extracted and de novo collagen production was measured. There was a decrease in the specific radioactivities of purified hepatic collagen (-75%) and albumin (-70%) relative to total hepatic protein, indicating that production of both of these proteins was specifically decreased. In fasted animals, the absolute hepatic collagen production was markedly decreased (-60%), while changes in absolute hepatic protein production were small (-15%). Using hybridization with specific DNA probes, we found that fasting causes about a 70% decrease in albumin mRNA, but the quantities of hepatic procollagen alpha 1(I) and alpha 2(I) mRNAs were unchanged. These results are consistent with regulation of albumin production during fasting by modulation of mRNA levels. The inhibition of hepatic collagen production in fasted animals, however, appears to be modulated at a posttranscriptional level or may result from increased degradation. This response differs from the pretranslational regulation of collagen synthesis in extrahepatic tissues during fasting. Furthermore, our results suggest that decreased body weight could be a potentially complicating variable in studies of collagen metabolism and fibrogenesis in the liver.

Albumins↗