Primary care is medicine's dinosaur.
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Career Choice↗
Biomedical subjects
B C Williams
Publications and source records attributed to B C Williams.
Congenital chloride losing enteropathy associated with tophaceous gouty arthritis.
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Adult↗
A lack of effect of captopril on platelet aggregation in patients with congestive heart failure.
We have studied the acute and chronic effects of an ACE inhibitor (captopril) on platelet function and the renin-angiotensin system in patients with congestive heart failure. Plasma concentrations of angiotensin II fell significantly after a single dose of captopril (25 mg) and during long-term treatment with captopril (2 weeks, 75 mg/day). Plasma renin activity increased significantly after both the single and repeated doses. Captopril did not affect ADP-induced platelet aggregation or concentrations. It seems unlikely that circulating angiotensin II affects ADP-induced platelet aggregation in patients with congestive heart failure.
Angiotensin II↗
Posture determines the nature of the interaction between angiotensin converting enzyme inhibitors and loop diuretics in patients with chronic cardiac failure.
The effects of inhibition of the renin angiotensin aldosterone system on the natriuretic and diuretic actions of an intravenous dose of frusemide 40 mg in patients with chronic cardiac failure maintained on oral diuretics were studied in the supine and erect positions. In the patients studied in the supine position the total 4 hour diuresis was decreased from 995 (92) ml to 668 (66) ml and the total 4 hour natriuresis fell from 105 (14) mmol to 67 (14) mmol following the administration of captopril. Creatinine clearance fell from 87 (8) ml/minute to 52 (15) ml/minute. In the patients studied in the erect position the total 4 hour diuresis was 596 (87) ml without captopril and 562 (83) ml with captopril. Total 4 hour natriuresis was 71 (13) mmol without captopril and 65 (9) mmol with captopril. Creatinine clearance was reduced by captopril from 82 (7) ml/minute to 47 (12) ml/minute. The reduction in the diuretic and natriuretic response to frusemide caused by captopril in the supine position is mediated through a fall in glomerular filtration rate. However, in the erect position, which is associated with even further increases in activity of the renin angiotensin aldosterone system, the reduction in diuresis and natriuresis that a fall in glomerular filtration rate would cause is offset by abolition of the rise in sodium retaining hormones, angiotensin II and aldosterone that mediate the antinatriuretic effect of the erect position.
Aged↗
Adrenergic and cholinergic regulation of cortisol secretion from the zona fasciculata/reticularis of bovine adrenal cortex.
Inner zone cells, isolated from bovine adrenal cortex, secrete cortisol in response to both adrenergic and cholinergic agonists. The response to adrenaline (and other catecholamines) appears during culture, is evident by 24 h and reaches a maximum by 48-72 h, but is absent in freshly isolated cells. Pre-incubation of cultured cells with adrenaline leads to homologous desensitisation; the possibility that this may explain the absent response in freshly isolated cells is discussed. Cells show a dose-dependent cyclic AMP response but no increased membrane phosphoinositide turnover. In agreement, cortisol secretion is blocked by beta-receptor, but not alpha-receptor, antagonists. Schild analysis established that the response occurs through binding to a beta 1-receptor subtype, consistent with adrenergic innervation as opposed to an effect of circulating catecholamines. In contrast, cortisol secretion to AcCh was present in both freshly isolated cells and those in culture, reaching a maximum by 48-72 h in culture. The response was specifically blocked by muscarinic, but not nicotinic, antagonists. No effect on cyclic AMP formation was observed, but dose-dependent stimulation of phosphoinositide turnover occurred. HPLC analysis of the time-course of appearance of 3H-inositol labelled head groups (from cells pre-labelled with 3H-inositol) confirmed that AcCh activates a phosphoinositidase C. Intracellular Ca2+ oscillations were also measured from fura-2 loaded single cells in response to AcCh. Together with other pharmacological studies, these observations establish that AcCh acts through a M3 muscarinic receptor subtype in these cells. The possible significance of these findings in vivo is discussed.
Acetylcholine↗
Acute administration of captopril lowers the natriuretic and diuretic response to a loop diuretic in patients with chronic cardiac failure.
Angiotensin-converting enzyme inhibitors suppress plasma concentrations of the sodium retaining hormones angiotensin II and aldosterone. This action should potentiate the natriuretic and diuretic effects of loop diuretics. Some studies indicate, however, that the introduction of angiotensin-converting enzyme inhibitors for the treatment of cardiac failure is associated with transient weight gain and the development of oedema. We have compared the natriuretic and diuretic response to intravenous frusemide 40 mg alone with the natriuretic and diuretic response to intravenous frusemide 40 mg following the administration of a single dose of captopril in 12 supine male patients with stable chronic cardiac failure. Captopril lowered the 4 h diuretic response to frusemide from 1160 (60) to 685 (77) ml (P less than 0.05) and the natriuretic response from 120 (9.6) to 68 (11.7) mmol (P less than 0.05). Creatinine clearance fell after captopril from 91 (7.2) to 57 (7.7) ml min-1 (P less than 0.05). Systolic and diastolic blood pressures were lower after the administration of captopril but these changes were not significant. Plasma renin activity rose from 3.8 (1.04) to 12.34 (2.94) ng ml h-1 (P less than 0.05) and plasma angiotensin II was reduced from 24.9 (5.05) to 8.14 (1.8) pg ml-1 (P less than 0.05). Plasma aldosterone concentrations were not significantly lower following captopril. Angiotensin-converting enzyme inhibitors cause an acute fall in creatinine clearance which may reduce the effects of loop diuretics and attention must be paid to diuretic dosage when initiating angiotensin-converting enzyme inhibitors for the treatment of cardiac failure.
Aged↗
11 beta-hydroxysteroid dehydrogenase in vascular smooth muscle and heart: implications for cardiovascular responses to glucocorticoids.
The enzyme 11 beta-hydroxysteroid dehydrogenase (11 beta-OHSD) converts the active glucocorticoid corticosterone to inactive 11-dehydrocorticosterone in the rat (or cortisol to cortisone in man), thereby protecting renal mineralocorticoid receptors from corticosterone or cortisol and allowing preferential access for aldosterone. We have previously demonstrated that cortisol-induced cutaneous vasoconstriction in man is potentiated by the 11 beta-OHSD inhibitor glycyrrhetinic acid, suggesting that 11 beta-OHSD may protect vascular corticosteroid receptors. In this study we report quantitation of 11 beta-OHSD bioactivity in homogenates of rat aorta, mesenteric artery, caudal artery, and heart, expressed as the percent in vitro conversion of 3H-corticosterone to 3H-11-dehydrocorticosterone. Nicotinamide adenine dinucleotide phosphate (NADP+)-dependent 11 beta-OHSD activity was found in all of these tissues and was significantly higher in resistance vessels than aorta (P less than 0.05) [without NADP+: caudal artery (4.2 +/- 0.2%) greater than mesenteric artery (2.5 +/- 0.7%) = heart (1.67 +/- 0.2%) greater than aorta (0.79 +/- 0.2%); with 200 microM NADP+: caudal artery (43.9 +/- 2.1%) greater than heart (20.6 +/- 1.0%) = mesenteric artery (17.7 +/- 3.1%) = aorta (11.4 +/- 0.4%); heart greater than aorta]. All of these were lower than renal cortex (29.4 +/- 1.8% without NADP+; 82.4 +/- 0.4% with NADP+; P less than 0.001). 3H-11-dehydrocorticosterone was the major metabolite of 3H-corticosterone (greater than 97% of 3H-corticosterone metabolized). Reduction of 3H-11-dehydrocorticosterone to 3H-corticosterone was not detected in these experiments. We also report localization of 11 beta-OHSD-like immunoreactivity by immunohistochemistry using antisera raised against rat liver 11 beta-OHSD, and of 11 beta-OHSD messenger RNA expression by in situ hybridization using complementary RNA probes transcribed from complementary DNA encoding rat liver 11 beta-OHSD. We found 11 beta-OHSD immunoreactivity and messenger RNA expression in vascular and cardiac smooth muscle cytoplasm but not in endothelium. Thus, 11 beta-OHSD is appropriately sited to modulate access of corticosterone to vascular receptors and could influence vascular resistance, cardiac output and thereby blood pressure.
11-beta-Hydroxysteroid Dehydrogenases↗
Dose-dependent effects of angiotensin II, acetylcholine and vasopressin on the cytosolic concentration of Ca2+ in suspension primary cultures of zona fasciculata/reticularis cells from bovine adrenal cortex.
The effects of angiotensin II (AII), acetylcholine and vasopressin on the intracellular concentration of Ca2+ have been little studied in adrenocortical cells from the zona fasciculata/reticularis (ZFR). Primary cultures of bovine ZFR cells maintained in suspension cultured for 72 h produce cortisol in response to AII (0.1 microM), acetylcholine (0.1 mM) and vasopressin (1 microM). This response is accompanied by a breakdown of membrane phosphoinositides from [3H]inositol-prelabelled cells. Using cells loaded with the Ca2+ indicator fura-2, the intracellular concentration of Ca2+ was measured in response to increasing doses of all three agonists and found to increase in a graded fashion in each case. The basal intracellular concentration of Ca2+ was 75 +/- 3 nM (mean +/- S.E.M., n = 52), rising to a maximum 1.82 +/- 0.14-fold (n = 6) for AII (0.1 microM), 1.35 +/- 0.05-fold (n = 7) for acetylcholine (0.1 mM) and 1.27 +/- 0.10-fold (n = 6) for vasopressin (1 microM). In the case of AII and acetylcholine, agonists were added sequentially in medium of normal extracellular Ca2+ concentration (1.2 mM) or in medium in which the Ca2+ concentration was buffered to approximate to the intracellular concentration of Ca2+ (75-100 nM). Evidence was thereby obtained that both AII and acetylcholine mobilize a common intracellular pool of Ca2+. Our findings suggest that these three agonists, all of which stimulate phospholipase C, increase intracellular Ca2+ through a mechanism which depends, at least in part, on the release of Ca2+ from a common intracellular pool.
Acetylcholine↗
Serotoninergic stimulation of aldosterone secretion in the rat in vivo: role of the renin-angiotensin system.
Serotoninergic control of aldosterone secretion in vivo was investigated in conscious rats with indwelling arterial cannulae. Serial blood samples were taken from the animals before and after i.p. administration of 1 ml (4 g/l) 5-hydroxytryptophan (5-HTP), the precursor of serotonin, or saline and they were analysed for 5-HTP, serotonin, 5-hydroxyindoleacetic acid, plasma renin activity (PRA), corticosterone, aldosterone, sodium and potassium concentrations. The role of the renin-angiotensin system was investigated in animals pretreated for 1 week with the angiotensin-converting enzyme inhibitor captopril (25 mg/day). 5-HTP caused a significant increase in all parameters within 45 min except for sodium and potassium. Saline administration showed no significant effect. Captopril pretreatment did not impair the increase in any parameter by 5-HTP, with the exception of the aldosterone response which was significantly attenuated, though not completely. The results show that administration of 5-HTP, which increases serum serotonin levels, stimulates PRA, aldosterone and corticosterone secretion. Captopril pretreatment inhibits the aldosterone response, suggesting that the aldosterone stimulatory properties of 5-HTP require the presence of angiotensin II, although it is unclear whether it acts in a mediatory or permissive capacity. The failure of captopril to inhibit the aldosterone response completely suggests the involvement of other mechanisms such as the hypothalamo-pituitary adrenal axis or a direct action of serotonin on the adrenal.
5-Hydroxytryptophan↗
Home health care. Comparison of patients and services among three types of agencies.
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Aged↗
Acetylcholine stimulates cortisol secretion through the M3 muscarinic receptor linked to a polyphosphoinositide-specific phospholipase C in bovine adrenal fasciculata/reticularis cells.
Zona fasciculata/reticularis (ZFR) cells, isolated from the bovine adrenal cortex, secreted cortisol in response to acetylcholine (AcCh). The response was present in freshly isolated cells and in cells maintained in primary culture, reaching a maximum after 48-72 h and thereafter declining. Cells maintained in primary culture for 72 h secreted cortisol with an ED50 at 1.2 x 10(-6) M. The potent inhibition of AcCh-stimulated secretion by atropine, and the relative ineffectiveness of nicotine or nicotinic antagonists, were consistent with a predominantly muscarinic response to AcCh in these cells. A selective M1-receptor agonist, McN-A-343, had no effect on cortisol secretion whereas the M3 antagonist, hexahydro-sila-difenidol, produced a dose-dependent inhibition of AcCh-stimulated cortisol secretion. These findings are consistent with AcCh mediating its effects on cortisol secretion through an M3 receptor. While AcCh had no effect on cAMP formation, a dose-dependent increase in [3H]phosphoinositols (identified using high-performance liquid chromatography (HPLC)) occurred in a manner that was not dependent on an influx of extracellular Ca2+. Detailed HPLC analysis of the formation of 3H-labelled phosphoinositols and glycerophosphoinositols from pre-labelled cells over the period 0-15 min showed that the earliest significant rise was in Ins(1,4,5)P3 at 5 s, followed by later rises in InsP1, InsP2 and Ins(1,3,4)P3. Additional studies using cells loaded with fura-2 indicator revealed a 1.6-fold increase in [Ca2+]i from a mean resting value of 75 nM in response to 10(-4) M AcCh. Furthermore, the rise in Ca2+ was not abolished by lowering extracellular Ca2+ to resting cytosolic levels, suggesting the mobilisation of an intracellular pool. These observations indicate that AcCh promotes rapid activation of a Ca2(+)-independent and polyphosphoinositide-specific phospholipase C, and that the Ins(1,4,5)P3 formed releases Ca2+ from an intracellular pool. The stimulation by AcCh of this signal transduction mechanism is consistent with our conclusion, based on the effects of the selective muscarinic agonist and antagonist on cortisol secretion, that the AcCh receptor is of the M3 subtype. We conclude that AcCh, acting through an M3 receptor coupled to phospholipase C, regulates cortisol secretion at the cellular level in bovine adrenal ZFR cells.
Acetylcholine↗
Predicting utilization of home health resources. Important data from routinely collected information.
This study examined the feasibility of using routinely collected information on patients enrolled in home health care to predict their subsequent use of services. Data were gathered from 1,984 episodes of care randomly sampled from home health care agencies of the Virginia Health Department. Age, sex, Medicare and Medicaid enrollment, referral source, medical diagnosis, and prognosis were used to predict the total number of visits, the duration of enrollment, and the intensity of service. Since the data were originally gathered to study the effects of the implementation of diagnosis-related groups (DRGs) on home health services, half of the patients were enrolled before and half after the implementation of DRGs. Using multiple linear regression analysis, significant amounts of variance in each measure of home health care utilization were explained by the predictor variables (R2 = 0.04 to 0.10). For example, after controlling for other predictor variables, age 75 years or older predicted longer durations of enrollment and lower intensities of service as compared with other age groups (P less than 0.05), and four of 14 diagnosis categories predicted at least one measure of utilization (P less than 0.05). Medicaid enrollment predicted longer durations of enrollment and lower intensities of service in home health care (P less than 0.05) in the post-DRG but not the pre-DRG period. These results demonstrate the value of routinely collected information in predicting the use of home health services. To develop more accurate estimates of needs for home health services for particular groups of patients, additional information on chronic functional impairments, informal caregiving, and the chronicity of needs may be useful.
Aged↗
Subclassification of beta-adrenoceptors responsible for steroidogenesis in primary cultures of bovine adrenocortical zona fasciculata/reticularis cells.
1. Forty eight hour primary cultures of purified bovine adrenocortical zona fasciculata/reticularis cells secreted hydrocortisone in response to stimulation with beta-adrenoceptor agonists. The observed order of potency was isoprenaline greater than noradrenaline greater than dobutamine greater than salbutamol greater than BRL37344. 2. Salbutamol acted as a partial agonist on these cells hence suggesting the presence of a beta 1-adrenoceptor. 3. Schild analysis of the hydrocortisone response to isoprenaline showed that the selective beta 1-antagonist practolol and the selective beta 2-antagonist ICI118,551 gave pA2 values of 6.85 and 7.17, respectively. These values were in close agreement with corresponding pA2 values previously obtained for the beta 1-adrenoceptor. 4. We conclude that beta 1-adrenoceptors are responsible for mediating catecholamine-stimulated hydrocortisone secretion from primary cultures of bovine zona fasciculata/reticularis cells.
Adrenergic beta-Agonists↗
Vasopressin stimulates cortisol secretion and phosphoinositide catabolism in cultured bovine adrenal fasciculata/reticularis cells.
Cells isolated from the zona fasciculata/reticularis (ZFR) of the bovine adrenal cortex and maintained in culture were found to secrete cortisol in response to vasopressin stimulation. The increased cortisol secretion was dose dependent, with a threshold response at 1 nM and a maximal response (1.68-fold over basal) at 0.1 microM. In cells cultured in the presence of [3H]inositol (to prelabel the membrane phosphoinositide pool), stimulation with vasopressin in the presence of LiCl (10 mM) resulted in a similar dose-dependent increase in labelling of the phosphoinositol fraction, with a maximal response (1.45-fold over basal) at 10 nM. The increased labelling of the phosphoinositol fraction was independent of extracellular Ca2+ as it was not abolished in medium with [Ca2+] buffered to intracellular resting levels. This suggests that vasopressin stimulation results in the activation of a phosphoinositidase C. It is probable that cortisol secretion by bovine ZFR cells in response to vasopressin is dependent upon activation of this Ca2(+)-independent phosphoinositidase C. However, the small magnitude of the cortisol secretory response makes it unlikely that vasopressin is a primary regulator of cortisol secretion in vivo.
Acetylcholine↗
Agonist-stimulated turnover of the phosphoinositides and the regulation of adrenocortical steroidogenesis.
Just as the recognition of the role of the phosphoinositides and phosphoinositols as a cellular signalling pathway has seen a dramatic advance in the last 10 years, so parallel investigations in adrenocortical cells have led to an equally dramatic increase in our understanding of the mechanisms involved in the control of adrenal steroidogenesis. In rat and bovine adrenocortical cells, the non-cAMP stimulatory agonists AII, acetylcholine and vasopressin have been shown to promote receptor/G-protein-mediated activation of a polyphosphoinositide-specific phospholipase C. In turn, studies in rat ZG and bovine ZG and ZFR cells have provided strong evidence for a causal relationship between the rapid and sustained formation of inositol 1,4,5-trisphosphate and DG by phospholipase C, and the subsequent increase in steroidogenesis in these cell types. In addition to describing the stimulatory effects of the various agonists on phospholipase C activity, this review has considered whether agonists may act through stimulation of phospholipase A2. No agonist can be said to act exclusively through phospholipase A2, and only AII can be said not to act through phospholipase A2 in adrenocortical cells. It seems unlikely that many studies will focus on this question in future unless an alternative physiological role for phospholipase A2 becomes apparent.
Adrenal Cortex↗
Tardive dyskinesia successfully treated with alprazolam.
Tardive dyskinesia is a disorder secondary to prolonged treatment (from 18 months to 3 years) with antipsychotic agents, affecting approximately 15% to 20% of patients. Tardive dyskinesia is characterized by difficulty controlling involuntary movements of the small muscle groups, producing tic-like reactions, muscle rigidity, and difficulty maintaining muscle tone. It is a chronic and unrelenting disorder which may be permanent if not successfully treated. The mechanism of action is thought to be secondary to dopamine hypersensitivity resulting from prolonged deprivation of dopamine on the part of dopamine-sensitive receptors. Theoretically, these receptors have been deprived of the neurotransmitter by chronic treatment with antipsychotic drugs, which are recognized as dopamine-blocking agents. We present a case in which alprazolam was successfully used in treating tardive dyskinesia.
Adult↗
Immunization coverage among preschool children: the United States and selected European countries.
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Child, Preschool↗
Excess injury mortality among children in the United States: comparison of recent international statistics.
Using data from the National Center for Health Statistics and the World Health Organization, child injury death rates in the US were compared to those of Canada, England and Wales, France, Netherlands, and Norway. Except for the 1981 Canadian figure, overall US childhood injury mortality was greater than childhood injury mortality rates of all countries studied during each year from 1980 to 1986. Injury mortality steadily declined in most other countries, whereas the US rate appears to be increasing. Attention to specific causes reveals that much of the difference is explained by motor vehicle injuries and homicide, but in every childhood age group US death rates due to drowning, firearms, homicide, poisoning, and fire are among the highest. Excess US injury mortality is largely attributable to deaths among children younger than 5 and older than 14 years of age, the most vulnerable groups in all countries. Especially high rates among US minorities account for little of the observed differences; for many injuries, the mortality rate of US nonblacks is several times those reported by the comparison nations. Behavioral strategies are inadequate to deal with excess death rates of this magnitude. Limiting exposure through regulation of handguns, greater use of public transportation, and affordable and accessible day care are among the measures that should be implemented.
Adolescent↗