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Biomedical subjects

C A Williams

Publications and source records attributed to C A Williams.

At least 145 records · Page 8Linked to original sources

Binding specificity and presynaptic action of anaphylatoxin C5a in rat brain.

Human anaphylatoxin C5a injected directly to the perifornical hypothalamus (PFH) of the rat elicits food intake in sated rats, an effect which mimics that of norepinephrine (NE) at the PFH. The ability of C5a to induce food intake is selectively blocked by the alpha-adrenergic antagonist phentolamine, confirming that C5a exerts its effects via an alpha-adrenergic receptor system. In this study specific C5a binding sites on rat brain slices were detected using 125I-C5a at 2.4 nM in the presence of unlabeled noncompeting C3a and competing C5a at 0.5 microM. To determine whether the in vivo activity of C5a was due to direct stimulation of an alpha-adrenergic receptor system or to indirect modulation via a specific C5a receptor, rats were pretreated at the PFH with C5ai, the "inactive" 74-desarginated derivative of C5a. C5ai blocked stimulation of feeding by C5a but had no effect on food intake elicited by NE, suggesting a presynaptic site for C5a activity. To determine whether C5a anaphylatoxin acts at presynaptic or postsynaptic sites, the ability of C5a and of NE to induce food intake in sated rats was compared before and after injection of the tyrosine hydroxylase inhibitor alpha-methyl-p-tyrosine (AMPT) to the PFH. AMPT would produce focal depletion of endogenous catecholamines by inhibition of catecholamine biosynthesis. Rats treated with AMPT failed to respond to C5a but ate excessively following NE, suggesting that C5a acts presynaptically, possibly to release NE. We propose that C5a acts at a specific C5a/C5ai receptor to modulate catecholamine activity at the brain site.

Anaphylatoxins↗

Toward an epidemiology of gastropathy associated with nonsteroidal antiinflammatory drug use.

The thesis of this paper is that gastropathy associated with nonsteroidal antiinflammatory drugs (NSAIDs) is the most frequent and, in aggregate, the most severe drug side effect in the United States. This work is based on a consecutive series of 2400 patients with rheumatoid arthritis followed prospectively for an average of 3.5 yr by ARAMIS, the American Rheumatism Association Medical Information System. We present a preliminary exploration of the magnitude of the problem, the population at risk, and the patients within that population who are at particularly high risk. Patients on NSAIDs had a hazard ratio for gastrointestinal (GI) hospitalization that was 6.45 times that of patients not on NSAIDs. Characteristically, high-risk patients for GI hospitalization and GI death are older, have had previous upper abdominal pain, have previously stopped NSAIDs for GI side effects, and have previously used antacids or H2-receptor antagonists for GI side effects. They also are frequently on corticosteroids. In contrast, patients attributing relatively minor symptoms to the drug tend to be younger and more frequently female. Our preliminary analysis is univariate and, as these variables are interdependent, firm conclusions regarding the relative importance of these risk factors will require reevaluating our data base as it is expanded using multivariate analysis. The syndrome of NSAID-associated gastropathy can be estimated to account for at least 2600 deaths and 20,000 hospitalizations each year in patients with rheumatoid arthritis alone.

Adult↗

Effects of opiates during baroreceptor and ergoreceptor induced changes in blood pressure.

Various opioids were used to investigate the role they might play in the cardiovascular responses to fatiguing isometric contractions. Changes in blood pressure were measured in cats anaesthetised with alpha-chloralose. Fatiguing isometric contractions of the hind limb muscles (ergoreceptor activation) were generated using a microprocessor controlled stimulator (50 Hz, 0.2 ms, 200-800 mV). Baroreceptor inactivation was elicited by carotid artery occlusion. Muscle contraction caused an increase in mean arterial pressure of 51 (SEM 12) mm Hg and carotid occlusion an increase of 56(9) mm Hg above resting levels in control conditions. Injection of dynorphin (0.5-5.0 micrograms.5 microliters-1) into the cerebral aqueduct just rostral to the 4th ventricle eliminated the pressor response to muscular contraction (mean arterial pressure at rest, 80-118 mm Hg: on fatigue, 72-129 mm Hg) but did not affect the pressor response to carotid occlusion in the same cats. Similarly, injections of met-enkephalin (1-100 micrograms.5 microliters-1) or beta-endorphin (10-100 micrograms.5 microliters-1) eliminated the ergoreceptor induced changes in mean arterial pressure during isometric contractions but had no effect on the changes caused by carotid occlusion. Pressor responses to nerve crush were not eliminated. These results support the suggestion that a catecholaminergic-opioidergic pathway in part mediates the cardiovascular responses to ergoreceptor afferent but probably not baroreceptor afferent input.

Animals↗

Patient education for people with schizophrenia.

This paper presents a rationale for greater nursing involvement in patient education for people with schizophrenia--specifically, providing information about the illness and ways to adapt to it (psychoeducation). It includes a conceptual framework for such education within the context of the nurse-patient relationship, plus an outline of suggested content. The proposed model is within the competency of professional psychiatric nurse generalists.

Adaptation, Psychological↗

Effects of cocaine on the human fetus: a review of clinical studies.

The abuse of cocaine in this country has reached epidemic proportions and has generated great concern for the effects of the drug on the fetus when used during pregnancy. Although educational campaigns cite adverse fetal effects as a deterrent to using the drug, there are limited data on which to base a true risk assessment. This paper reviews the published studies of pregnancy outcome in cocaine-abusing mothers, with special focus on structural malformations and other neonatal risks.

Cocaine↗

Perspectives on the hallucinatory process.

Hallucinations are common psychiatric symptoms and the hallucinating patient presents a number of nursing problems. Although psychiatric nurses have written fairly extensively about hallucinations as a clinical problem, little nursing research has tested commonly recommended nursing interventions. This paper presents a review of interdisciplinary research on hallucinations and synthesizes findings with clinical observations to suggest a number of areas needing greater stress in nursing practice and research. Aspects of a model proposed by Peplau (1963), Rector (1982), and Field (1985) are questioned. Improved assessments of hallucinating patients are recommended, with exploration of subtleties in the hallucinatory experience; and factors needing assessment are identified. Major emphasis is placed on the need to explore patient efforts at controlling hallucinations as a foundation for promoting patient self-monitoring and self-regulation of hallucinatory experience.

Autosuggestion↗

Toxic effects of azathioprine in rheumatoid arthritis. A national post-marketing perspective.

Concerns about the short-term and long-term toxic effects of azathioprine (AZA) have limited its use. Accordingly, we surveyed 393 AZA-treated rheumatoid arthritis (RA) patients, who were recruited and enrolled through a nationwide call to rheumatologists. Findings in these patients were compared with the findings, retrieved from the databank of the American Rheumatism Association Medical Information System, on 153 similarly treated RA patients. All 546 patients were surveyed prospectively, using the Health Assessment Questionnaire and information abstracted from hospital records. The 2 groups were closely similar in clinical characteristics. The most frequently reported side effects of AZA treatment were nausea, vomiting, and leukopenia. Gastrointestinal intolerance accounted for nearly 60% of therapy interruptions in 95 patients. Of 81 hospitalizations for all causes, only 8 may have been related in part to AZA, and no deaths were attributed to AZA therapy. No lymphomas or leukemias were encountered and the overall frequency of neoplasms was not significantly different from that seen in RA patients receiving conventional therapy. As used in the treatment of RA, AZA has a surprisingly benign profile with relatively few serious therapeutic mishaps.

Arthritis, Rheumatoid↗

The Hopelessness Scale for Children: psychometric properties with normal and emotionally disturbed adolescents.

The psychometric properties of the Hopelessness Scale for Children (HSC) were evaluated with a sample of 834 normal adolescents and 93 adolescent suicide attempters. Factor analyses studies revealed two factors with both groups. Internal consistency with item-total score correlations were acceptable, while moderate test-retest reliability was found over a 10-week period with the normal sample. Support for the validity of the HSC was provided via studies with the suicide attempter group in which positive correlations with depression and depressive attributional style were found. Predicted differences between the suicide attempters, an outpatient psychiatric sample, and normal controls were also found. However, some items did not appear to discriminate suicide attempters from controls. Results are discussed in terms of the utility of the HSC with adolescents and adolescent suicide attempters and with regard to differences between child and adult samples in hopelessness.

Adolescent↗

Thyroid function in a lizard, a tortoise and a crocodile, compared with mammals.

1. Thyroid activity was examined in the lizard, Trachydosaurus rugosus, the tortoise Chelodina longicollis and the crocodile, Crocodylus johnstoni, acclimated to 20-22 degrees C and 30-32 degrees C. Thyroidal uptake and release of 125I, plasma concentrations of T3 and T4 were measured as was resting oxygen consumption (at 30 degrees C) before and after both thyroidectomy and thyroxine injections. 2. All three species showed 125I uptake at both temperatures and showed no thyroidal release of 125I at 20-22 degrees C but exhibited thyroidal release of 125I (and presumably hormone secretion) at 30-32 degrees C. 3. Plasma concentrations of thyroxine ranged from 0.55 nM to 3.24 nM and triiodothyronine from 0.14 nM to 0.51 nM. 4. Neither thyroidectomy nor thyroxine injections had any effect on metabolic rate in 20-22 degrees C acclimated lizards. Thyroidectomy resulted in a significant decrease in metabolic rate in 30-32 degrees C acclimated lizards and tortoises and thyroxine injections resulted in significant increases in metabolism in 30-32 degrees C acclimated lizards, tortoises and crocodiles. 5. A comparison of thyroid parameters in reptiles and mammals concluded that although the reptilian thyroid is active at high temperatures it is still considerably less active than it is in mammals.

Alligators and Crocodiles↗

Vitamin E and Alzheimer's disease in subjects with Down's syndrome.

People with Down's syndrome (DS) are at high risk of developing Alzheimer's disease (AD). The gene coding for superoxide dismutase-/ on chromosome 21 resulting in excess activity of the enzyme with consequent risk of oxidative damage might account for the premature ageing. Vitamin E protects against such damage. Plasma vitamin E levels measured in 12 DS subjects with AD (8.19 +/- 0.77 micrograms/ml) were lower (P less than 0.05) than in 12 DS controls (9.43 +/- 1.57 micrograms/ml). It is suggested that there may be an interaction between risk of AD and the protective action of vitamin E.

Adult↗

Effects of ingesting glucose and some of its polymers on serum glucose and insulin levels in men and women.

Twelve men and 10 women were given maltodextrin (DE20) at various dose levels after an overnight fast. Similar studies were carried out with glucose, maltose and another maltodextrin (DE5). It was found that within each sex the serum glucose and insulin responses were not influenced by the physical form of glucose ingested over a 90-min period. However, the serum glucose response to glucose and to its polymers was found to be dose-dependent in the men but not in the women. The serum insulin response was dose-dependent in both sexes. At any glucose dose level the serum insulin response was approximately 40% greater in men compared to women.

Blood Glucose↗

Effect of different body postures on the pressures generated during an L-1 maneuver.

Changes in blood pressure, intrathoracic pressure, heart rate and the electromyographic activity of various muscle groups were determined while nine male subjects performed 15-s L-1 straining maneuvers at four spine-to-thigh angles (70, 84, 94, and 105 degrees) and two seatback angles (30 and 60 degrees). There was no significant difference between the changes in these variables due to the different body positions. At the onset of the L-1, arterial pressure immediately increased to 195 +/- 5 mm Hg, but fell progressively during the next 5 s to 160 +/- 5 mm Hg. It remained constant during the next 5 s of the maneuver and then recovered to 180 +/- mm Hg during the last 5 s of the maneuver. Esophageal pressure followed essentially the same pattern of response, but heart rate progressively increased during the entire L-1. No one muscle group was utilized more than another. Inflation of an anti-G suit to 4 PSI had no effect on the variables measured. Generation of high arterial pressures during L-1 maneuvers is transitory and not affected either positively or negatively by altering subject body position.

Adult↗

Apparent G syndrome presenting as neck and upper limb dystonia and severe gastroesophageal reflux.

We have studied a 3-month-old boy with severe gastroesophageal reflux, feeding difficulties, neck and upper limb dystonia, abnormal ears, normal genitalia, and anatomically apparently normal larynx and trachea. Initially diagnosed as suffering from Sandifer "syndrome," he was treated with a gastrostomy and Nissen fundoplication. However, his characteristic facial appearance subsequently led to the diagnosis of G syndrome.

Abnormalities, Multiple↗

The influence of straining maneuvers on the pressor response during isometric exercise.

Experiments were performed to determine to what extent increments in esophageal and abdominal pressure would have on arterial blood pressure during fatiguing isometric exercise. Arterial blood pressure was measured during handgrip and leg isometric exercise performed with both a free and occluded circulation to active muscles. Handgrip contractions were exerted at 33 and 70% MVC (maximum voluntary contraction) by 4 volunteers in a sitting position and calf muscle contractions at 50 and 70% MVC with the subjects in a kneeling position. Esophageal pressure measured at the peak of inspirations did not change during either handgrip or leg contractions but peak expiratory pressures increased progressively during both handgrip and leg contractions as fatigue occurred. These increments were independent of the tensions of the isometric contractions exerted. Intra-abdominal pressures measured at the peak of either inspiration or expiration did not change during inspiration with handgrip contractions but increased during expiration. During leg exercise, intraabdominal pressures increased during both inspiration and expiration, reaching peak levels at fatigue. The arterial blood pressure also reached peak levels at fatigue, independent of circulatory occlusion and tension exerted, averaging 18.5-20 kPa (140-150 mm Hg) for both handgrip and leg contractions. While blood pressure returned to resting levels following exercise with a free circulation, it declined by only 2.7-3.8 kPa after leg and handgrip exercise, respectively, during circulatory occlusion. These results indicate that straining maneuvers contribute 3.5 to 7.8 kPa to the change in blood pressure depending on body position.

Blood Pressure↗

ACTH regulation of cholesterol movement in isolated adrenal cells.

Confluent bovine adrenal cell primary cultures respond to stimulation by adrenocorticotropin (ACTH) to produce steroids (initially predominantly cortisol and corticosterone) at about one-tenth of the output of similarly stimulated rat adrenal cells. The early events of steroidogenesis, following ACTH stimulation, have been investigated in primary cultures of bovine adrenal cortical cells. Steroidogenesis was elevated 4-6-fold within 5 min of exposure to 10(-7) M ACTH and increased linearly for 12 h and declined thereafter. Cholesterol side-chain cleavage (SCC) activity was increased 2.5-fold in mitochondria isolated from cells exposed for 2 h to ACTH and 0.5 mM aminoglutethimide (AMG), even though cytochrome P-450scc only increases after 12 h. Mitochondrial-free cholesterol levels increased during the same time period (16.5-25 micrograms/mg of protein), but then both cholesterol levels and SCC activity declined in parallel. More prolonged exposure to ACTH prior to addition of AMG caused the elevation in mitochondrial cholesterol to more than double, possibly due to enhanced binding capacity. Early ACTH-induced effects on cellular steroidogenesis result from these changes in mitochondrial-free cholesterol. The maximum rate of cholesterol transport to mitochondria in AMG-blocked cells was consistent with the maximum rate of cellular steroidogenesis. Cycloheximide (0.2 mM) rapidly blocked (less than 10 min) cellular steroidogenesis, cholesterol SCC activity, and access of cholesterol to cytochrome P-450scc without affecting mitochondrial-free cholesterol. Exposure of confluent cultures to the potent environmental toxicant, 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) (10(-8) M), for 24 h prior to ACTH addition decreased the rates of ACTH- and cAMP-stimulated steroidogenesis but did not affect the basal rate. In both cases, the effectiveness of TCDD increased with time of exposure to the stimulant. Although cholesterol accumulated in the presence of ACTH and AMG (13-28 micrograms/mg), pretreatment of cells with TCDD caused a decrease in mitochondrial cholesterol (13-8 micrograms/mg). The effect of TCDD was produced relatively rapidly (t1/2 approximately 4 h). Since even in the absence of TCDD, the mitochondria of ACTH-stimulated cells also eventually lose cholesterol (after 2 h) TCDD pretreatment may increase the presence of a protein(s) that cause this mitochondrial-cholesterol depletion following stimulation by ACTH or cAMP.(ABSTRACT TRUNCATED AT 400 WORDS)

Adrenal Cortex↗