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Biomedical subjects

F Davis

Publications and source records attributed to F Davis.

At least 55 records · Page 3Linked to original sources
PubMed1987

Sustained hemodynamic improvement during long-term therapy with levodopa in heart failure: role of plasma catecholamines.

Long-term therapy with oral sympathomimetic amines in patients with heart failure has been limited by the eventual development of diminished pharmacologic efficacy. However, a previous investigation in five subjects with heart failure suggested that long-term ingestion of levodopa, which is decarboxylated endogenously to dopamine, produces a sustained improvement in cardiac function. In the present study, levodopa was administered orally (1.5 to 2.0 g) to 14 patients with heart failure while hemodynamic responses and plasma catecholamines were monitored. Initially, an increase in cardiac index and stroke volume index was accompanied by a decline in systemic vascular resistance, mean pulmonary capillary wedge pressure and mean right atrial pressure. Heart rate and mean arterial pressure were unchanged. Plasma concentrations of dopamine rose substantially after drug ingestion and correlated significantly with changes in cardiac index (r = 0.73, p less than 0.05). After 12 weeks of treatment with levodopa, the changes in cardiac index, stroke volume index, systemic vascular resistance and plasma dopamine levels persisted (n = 12 patients). Moreover, a significant decrease occurred in the heart rate at rest. Although there was an initial tendency for plasma norepinephrine concentrations to increase, a return to control levels was documented after long-term treatment. Thus, tolerance to the hemodynamic actions of levodopa did not develop during long-term administration of the drug. The hemodynamic responses observed can be ascribed to the activation of beta 1-adrenoceptors and dopamine1 receptors by dopamine generated from levodopa. The dopamine2 activity of dopamine does not appear to be responsible for the improvement in cardiac performance produced by levodopa.

Adult↗
PubMed1987

Effects of long-term therapy with oral piroximone on resting hemodynamics, peak aerobic capacity, and the anaerobic threshold in patients with heart failure.

Piroximone (MDL 19205), a new imidazole derivative with positive inotropic and vasodilating properties, was administered to 10 patients with congestive heart failure. After acute intravenous (0.90 +/- 0.12 mg/kg, mean +/- SEM) and oral (1.41 +/- 0.18 mg/kg) administration, cardiac index and stroke volume index increased and were accompanied by a decline in systemic vascular resistance, pulmonary capillary wedge pressure, and right atrial pressure. Mean arterial pressure was unchanged, but heart rate increased modestly after intravenous piroximone. An increase in premature ventricular contractions was documented in four patients after drug administration. Seven of the 10 patients completed 12 weeks of therapy with piroximone; one patient withdrew after 8 weeks because of deterioration in clinical status; one developed severe ventricular arrhythmias and died after 5 days of treatment; and a drug-induced hepatitis was documented in one subject at 4 weeks. No significant improvement in oxygen uptake at peak exercise and the anaerobic threshold was observed after long-term treatment (assessed at 6 and 12 weeks). Hemodynamic responsiveness to piroximone was sustained in five patients who underwent repeat evaluation at 12 weeks. Thus, long-term treatment with piroximone was not associated with an improvement in maximal and submaximal exercise capacity in patients with congestive heart failure. Serious adverse effects were observed with the administration of this drug.

Administration, Oral↗
PubMed1986

Pre- and postnatal influence of an estrogen antagonist and an androgen antagonist on differentiation of the sexually dimorphic nucleus of the preoptic area in male and female rats.

The volume of the sexually dimorphic nucleus in the preoptic area (SDN-POA) of the rat brain is severalfold larger in adult male rats than in adult females. This sex difference in brain structure was previously shown to develop under the influence of androgenic and estrogenic hormones during the perinatal period. We tried to clarify the differential role played by androgens and estrogens during development and differentiation of the SDN-POA by treating male and female rats during an extended pre- and postnatal period either with the estrogen antagonist tamoxifen or with the androgen antagonist cyproterone acetate. Treatment with tamoxifen did not alter serum levels of testosterone in male rats during the perinatal period, but it inhibited development and differentiation of the SDN-POA. Pre- and postnatal treatment of male rats with cyproterone acetate resulted in female phenotypic appearance, but it had no influence on differentiation of the SDN-POA. Perinatal treatment of female rats with tamoxifen resulted in permanent anovulatory sterility, but did not influence SDN-POA differentiation. Treatment of female rats with cyproterone acetate had no influence on SDN-POA differentiation or on the capacity to ovulate. Since pre- and postnatal treatment of male rats with cyproterone acetate is known from previous studies to femenize sexual behavior patterns and to retain the mode for cyclic gonadotropin release, and since the same treatment did not influence differentiation of the SDN-POA in the present study, it may be concluded that the SDN-POA is not directly involved in the control of female sexual behavior and in the control of the gonadotropic hormone release pattern.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1985

Respiratory symptoms among glass bottle makers exposed to stannic chloride solution and other potentially hazardous substances.

Concern about upper respiratory tract irritation and other symptoms among workers at a glass bottle manufacturing plant led to an epidemiologic and an industrial hygiene survey. Questionnaire responses from 35 hot end and 53 cold end workers indicated that the incidence of wheezing, chest pain, dyspnea on exertion, and cough was significantly elevated among hot end workers. Among both smokers and nonsmokers, hot end workers reported higher, but not significantly higher, rates of wheezing and chest pain. Among smokers, hot end workers reported significantly higher rates of dyspnea on exertion and cough than did cold end workers. Data suggest that reported exposure to stannic chloride solution likely caused these symptoms. The industrial hygiene survey, conducted when stannic chloride use had been reduced, cleaning had been done, and ventilation improved, focused on measuring air contaminants that might possibly cause symptoms. Levels of hydrogen chloride, which apparently was formed by the combination of stannic chloride and water in the presence of heat, were elevated. The finding of increased prevalence of respiratory symptoms among hot end workers was consistent with this exposure. Recommendations were made to reduce hazardous exposures at this plant. Individuals responsible for occupational health should be aware that relatively benign substances, such as stannic chloride and water, can combine spontaneously to form hazardous substances.

Adult↗
PubMed1984

Pre- and postnatal influence of testosterone propionate and diethylstilbestrol on differentiation of the sexually dimorphic nucleus of the preoptic area in male and female rats.

The volume of the sexually dimorphic nucleus in the preoptic area (SDN-POA) of the rat brain is several fold larger in males than in females. When female rats were treated pre- and postnatally with testosterone propionate (TP) or with diethylstilbestrol (DES) they became anovulatory and their SDN-POA developed equivalent in size to that of normal males. Identical treatment of male rats resulted in deficient testicular development, but had no influence on SDN-POA volume. The results indicate that the gross morphological sex difference in SDN-POA volume can exclusively be controlled by the hormonal environment during the critical period of sexual brain differentiation, and that non-steroidal estrogens are just as effective as convertible androgens in stimulating SDN-POA differentiation.

Animals↗
PubMed1982

Differentiation of the sexually dimorphic nucleus in the preoptic area of the rat brain is determined by the perinatal hormone environment.

The volume of a sexually dimorphic nucleus in the preoptic area (SDN-POA) of the rat brain is several fold larger in males than in females. When female rats were treated pre- and postnatally with testosterone propionate (TP) their SDN-POA developed equivalent in size to that of normal males. The results indicate that the gross morphological sex difference in SDN-POA volume is exclusively controlled by the hormonal environment during the critical period of sexual brain differentiation.

Animals↗
PubMed1982

Growth factors in Hodgkin's disease.

Tumor nodules from spleens removed at staging laparotomy for nodular sclerosing Hodgkin's disease were grown as fragment cultures in vitro. These cultures could be maintained in vitro for up to 2 months and consisted of 90% large, adherent multinuclear and mononuclear cells. Immunologic markers and enzyme histochemistry suggested that the cultured cells belonged to the monocyte/macrophage lineage. Supernatants from these cell cultures were then assayed for the monokine Interleukin I and for fibroblast stimulatory factors, which were both present. These results are discussed in considering Hodgkin's disease as a neoplasm of the monocyte/macrophage lineage, capable of producing functionally active mediators that may account for the histopathologic appearance observed.

Cells, Cultured↗
PubMed1981

Pharmacology of Escherichia coli-L-asparaginase polyethylene glycol adduct.

The polyethylene glycol (PEG) adduct of Escherichia coli L-asparaginase was administered intravenously to 4 patients with chemotherapy refractory cancers. The PEG-enzyme in plasma exhibited a half-life of 16-25 days. Doses of 250IU/m2 or greater reduced plasma asparagine to undetectable levels for as long as enzyme was detectable in plasma. All doses of enzyme administered (250-1000 IU/m2) caused similar increases in plasma aspartate, i.e. no dose-response relationship. Pleural fluid and ascites contained detectable enzyme but at a value 10-15% of simultaneously drawn plasma levels. Toxicity in this small group of patients was minimal; nausea and transient fever predominated. There were no clinical signs of PEG-asparaginase-induced pancreatitis, renal dysfunction, hypocalcemia and hyperglycemia. No patient developed evidence of a PEG-asparaginase allergic reaction; no patient formed antibodies to asparaginase or PEG-asparaginase. Two patients with large cell lymphoma showed a partial response to treatment.

Antineoplastic Agents↗
PubMed1979

Host-cell reactivation of UV-irradiated adenovirus in Cockayne syndrome.

Measurements of the host-cell reactivation (HCR) of mutagen-treated virus provides a very sensitive tool for detecting abnormal DNA repair. The best example of the utility of HCR studies in the examination of the DNA-repair capacity of human cells has come from studies of cells from the UV-sensitive repair-deficient xeroderma pigmentosum (XP) patients. We have examined the HCR of UV-treated adenovirus type 5 (Ad5) and type 2 (Ad2) in cells from patients with Cocayne syndrome (CS), another sun-sensitive syndrome whose cells also exhibits UV-sensitivity in culture. Comparisons with obligate heterozygotes and normal controls failed to reveal an abnromality in the HCR capacity of the CS cells. As the abnormality in DNA metabolism in CS appears to be in a late step in excision repair, a bypass mechanism may exist in these cells for circumventing the defect in the repair of viral DNA.

Adenoviridae↗