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Biomedical subjects

R Woods

Publications and source records attributed to R Woods.

At least 109 records · Page 6Linked to original sources

Vasoconstrictor role for vasopressin in conscious, sodium-depleted rats.

To define the role of vasopressin as a vasoconstrictor hormone in sodium depletion, systemic hemodynamics and regional blood flow distribution were examined in conscious Sprague-Dawley rats after 6 days of a low-sodium diet. Studies were performed after selective or combined blockade with the vasopressin antagonist [d(CH2)5Tyr(Me)]AVP (AVPA), enalaprilat (CEI), and phentolamine (PHENTOL). Plasma levels of vasopressin were increased significantly after CEI and increased further after PHENTOL and CEI plus PHENTOL. AVPA had no effect on blood pressure, whether given alone or in the presence of PHENTOL, CEI, or CEI plus PHENTOL. Significant falls in peripheral vascular resistance associated with reflex increases in cardiac output were observed when AVPA was given to animals pretreated with either CEI or PHENTOL but not both. AVPA alone produced no significant changes in regional blood flow distribution, but a vasoconstrictor action of vasopressin in the renal vascular bed was revealed after prior treatment with CEI or PHENTOL. Muscle blood flow was also increased in the PHENTOL plus AVPA group compared with the PHENTOL group. No significant additional effects of AVPA were revealed by pretreatment with CEI, PHENTOL, or CEI plus PHENTOL for mesenteric, hepatic, splenic, or cerebral vascular beds. It is suggested that vasopressin acts as a vasoconstrictor hormone in conscious sodium-depleted rats when either the renin-angiotensin system or alpha-adrenergic system is inhibited but not when both systems are blocked. The renal vascular bed is an important site for vasopressin-induced vasoconstriction under these circumstances.

Adaptation, Physiological↗

Triiodothyronine binding in adult rat brain: compartmentation of receptor populations in purified neuronal and glial nuclei.

In order to investigate the localization of nuclear T3 receptors in adult rat brain, we have developed a technique for separating neuronal and glial nuclei, and compared nuclear T3 binding in both fractions. Glial and neuronal nuclear populations were prepared by homogenization of the whole brain except the cerebellum, followed by discontinuous density gradient centrifugation in 2.4 and 2.2 M sucrose. For purposes of comparison, liver nuclei were prepared by centrifugation in 2.4 M sucrose. Microscopic examination of the nuclei confirmed the purity of the two nuclear fractions to be above 90% with minimal extranuclear contamination. T3 binding studies were performed on the washed nuclear fractions using saturation analysis techniques. Maximum binding (Bmax) and dissociation constant (Kd) were obtained by nonlinear least-squares regression analysis. After 30 min incubation at 37 C, Bmax in neuronal nuclei was 1203 +/- 118 fmol/mg DNA (mean +/- SE) (n = 6), in comparison with 196 +/- 14 fmol/mg DNA in glial nuclei (n = 7). The corrected value for Bmax in glial nuclei, assuming 8% neuronal nuclear contamination, was 100 fmol/mg DNA. Bmax in liver nuclei was contamination, was 100 fmol/mg DNA. Bmax in liver nuclei was 299 +/- 38 fmol/mg DNA (n = 6). The Kd values were 0.38 +/- 0.04 nM, 0.34 +/- 0.05 nM, and 0.33 +/- 0.04 nM in neuronal, glial, and liver nuclei, respectively. The specificity of T3 binding to the nuclear receptor in both neuronal and glial nuclei was studied in competition studies, and revealed closely similar relative binding affinities (T3 greater than T4 greater than rT3) in both. We conclude that the higher T3 binding capacity of neuronal nuclei may be related to their higher protein synthetic ability, suggesting that T3 may be of importance in a rapid structural turnover in these cells. The effect of T3 on myelination in glial cells may be mediated through the nucleus.

Animals↗

Mitomycin and mitoxantrone in previously treated patients with advanced breast cancer.

A total of 56 heavily pretreated patients with advanced breast cancer were treated with the combination mitomycin and mitoxantrone. Partial responses were seen in ten of 56 patients (18%), or ten of 44 (23%) completing two courses, while 18 (32%) had stable disease. Responses were seen in eight patients failing doxorubicin. The median duration of response was 26 weeks, with responders surviving a median of 37 weeks. A total of 59% of the courses were associated with World Health Organization grade 3 or 4 neutropenia (less than 1.0 X 10(9) cells/L). Nausea and vomiting were minimal. Mitomycin and mitoxantrone has activity in heavily pretreated patients with advanced breast cancer.

Antineoplastic Combined Chemotherapy Protocols↗

Phase I and pharmacokinetic study of tiazofurin (NSC 286193) administered by 5-day continuous infusion.

A phase I and pharmacokinetic study of tiazofurin (NSC 286193), a C-nucleoside that inhibits IMP dehydrogenase, has been completed. The drug was administered by continuous infusion over 5 days. The maximum tolerated dose was 1650 mg/m2 per day, neurological toxicity being the dose-limiting factor. Gastrointestinal and hematological toxicity were mild. A definite relationship exists between dosage and steady-state levels. The plasma clearance was 29.13 (+/- SD 4.05) ml/min per m2. No complete or partial remissions were demonstrated among the 18 patients treated at five dose levels between 550 mg/m2 and 2200 mg/m2 per day.

Adult↗

One month's insulin treatment of type II diabetes: the early and medium-term effects following insulin withdrawal.

In order to see if subcutaneous insulin treatment of type II diabetes might produce lasting physiologic changes, ten patients received one month's insulin treatment under strict dietary supervision. When compared to the pretreatment period, 48 hours after discontinuing insulin treatment fasting plasma glucose had fallen (P = 0.005), fasting serum insulin had risen (P = 0.005), and fasting hepatic glucose production measured by 3H-3-glucose turnover had fallen (P = 0.008). The metabolic clearance rate of glucose measured with the glucose clamp rose significantly after treatment at insulin infusion rates of 40 mU m-2 min-1 (P = 0.015) and 400 mU m-2 min-1 (P = 0.012). The serum insulin and C-peptide responses to oral glucose improved after the treatment in association with the improvement in glucose tolerance, but the plasma glucose response was unchanged. Six other type II diabetic patients who received only dietary supervision did not show significant changes in these variables. Six weeks after discontinuing insulin, the patients' fasting hepatic glucose production was still reduced compared to pretreatment (P = 0.028) and insulin action was still improved at both the lower (P = 0.028) and the higher (P = 0.028) insulin infusion rates, but the fasting plasma glucose and insulin and C-peptide responses to oral glucose had returned to pretreatment values. The improvement in glucose tolerance and beta-cell function induced by insulin treatment seems to be of more limited duration than the improvements in basal hepatic glucose production and in insulin action.

Aged↗

Antenatal prediction of sex.

Current recommendations suggest that prospective parents be informed of the fetal sex following an amniocentesis--if the parents express a desire for that information. Genotype does not in all cases accurately predict the appropriate sex of rearing. A case is discussed involving an infant with ambiguous genitalia who prior to birth had been designated a male, based on genotype obtained following amniocentesis. Caution is urged in predicting sex antenatally.

Adult↗

Conformational analysis and active site modelling of angiotensin-converting enzyme inhibitors.

The discovery of captopril as a potent, orally active inhibitor of angiotensin-converting enzyme (ACE) led to the recent development of many series of novel structures with similar biological activity. To date, however, all of these inhibitors are flexible or semiflexible molecules, and there is therefore no clear definition of the conformational requirements for ACE inhibition. In an effort to solve this problem, we have carried out conformational energy calculations on a series of eight structurally diverse ACE inhibitors. Comparison of the low-energy conformations available to these molecules leads to the conclusion that there is a common low-energy conformation throughout the series. The calculations thus define the structural and conformational requirements for ACE inhibition. Expansion of this model to the receptor level has been achieved by considering possible alternative receptor sites for each of the molecules in its proposed biologically active conformation and leads to an active-site model for ACE which may be useful for the design of further inhibitors.

Angiotensin-Converting Enzyme Inhibitors↗

Direct immunofluorescence of normal skin in rheumatoid arthritis.

The clinical significance of previously described immunoglobulin and complement deposition in the superficial dermal vessel walls of patients with rheumatoid arthritis is unknown. In the present study, skin biopsies were obtained from the normal forearm and buttock of 48 unselected patients with rheumatoid arthritis and were examined by direct immunofluorescence (IF) for the presence of immunoglobulin (IgG,A,M) and complement (C3) in the vessel walls. Deposits of C3, IgM or IgG were detected in 10 patients. Five patients had deposits at the forearm sample alone, four patients had deposits at both biopsy sites, while one patient was positive at the buttock alone. Clinical features were similar in patients with and without vessel IF. However, patients with IF were significantly more seropositive with lower levels of complement and raised levels of serum IgA and IgM. There was also an increased level of circulating IgG immune complexes in these patients. Further analysis following exclusion of seronegative patients revealed similar results. This study suggests that the presence of vessel IF identifies a subgroup of patients who have evidence of more severe immunological disturbance.

Antibodies↗

The fertility transition in nineteenth-century England and Wales: a social class model?

"The changing relationship between fertility and the standard of living is examined in the long term. The model presented provides a means of focusing on the cross-sectional association between fertility, especially marital fertility, and social class during the nineteenth-century fertility transition in England and Wales. An inverse relationship is revealed by all four of the perspectives adopted, but the problems inherent in defining social classes and the significance of fertility behaviour particular to occupations diminish the value of very broad generalizations."

Birth Rate↗

Cyclical Cushing's disease: two distinct rhythms in a patient with a basophil adenoma.

A 71-yr-old woman with clinical signs of Cushing's syndrome was studied continuously for an extended period after demonstration of a paradoxical response to dexamethasone. She proved to have a corticotroph cell adenoma of the pituitary which caused secretion of ACTH and cortisol in two distinct rhythms. One rhythm consisted of a period of 40 days of excess cortisol production, followed by a period of 60-70 days of normal production. During the period of excess cortisol production there was a second rhythm, consisting of peaks of cortisol production every 3-6 days with intervening troughs of normal cortisol production. Prolonged clinical remission followed transphenoidal surgery, but the pituitary still has the ability to provoke abnormal amounts of cortisol secretion, as occurred during a postoperative dexamethasone suppression test. The long duration of normal cortisol production phases in this patient demonstrates the difficulty in excluding Cushing's syndrome in patients with suggestive clinical symptoms but normal serum and urinary cortisol levels if these tests are measured for a single short phase of several days.

Adenoma, Basophil↗

Prevention of transmission of hepatitis B in dental practice.

Hepatitis B virus (HBV) is transmitted by infected blood and possibly saliva; faecal-oral transmission is also possible. Infected material is transmitted mostly by the parenteral route. Hence, the transmission of HBV in the dental surgery should be prevented by the routine exercise of good clinical hygiene. As part of patient assessment information on recent hepatitis should be sought. Patients may carry HBV and be infectious from 1 to 4 months after contracting the disease. During this period the surface antigen (HBsAg) can be detected in blood. Symptoms generally appear from 2 to 4 months after infection. High risk groups in the community should be recognized. In communities where the disease is widespread this may include most of the population. Elective dental treatment for patients likely to be infectious should be postponed until the infectious stage has passed; this can be confirmed by showing the absence of HBsAg in blood. A high standard of clinical hygiene, including the routine use of disposable needles for injections, single dose containers for drugs to be injected, sterilized instruments and personal cleanliness before and after treating patients, is essential to prevent transmission of HBV. More stringent precautions are necessary when treating persons likely to be infectious. Although the introduction of an immunization programme to protect dentists and clinical staff is imminent proper clinical hygiene will continue to be essential to safeguard both patients and clinicians.

Carrier State↗