Biomedical subjects

T W Wilson

Publications and source records attributed to T W Wilson.

At least 37 records · Page 2Linked to original sources

PubMed1998

Transcutaneous delivery of prostaglandin E1: in vitro and laser doppler flowmetry study.

The aim of this study was to assess the rate and extent of transcutaneous delivery of prostaglandin E1 (PGE1) from various formulations [liposomal, novel biphasic, and nonliposomal (oil/water cream) delivery systems] in vitro using diffusion cells and in vivo using laser doppler flowmetry, to aid in the development of a topically active preparation for the treatment of male sexual dysfunction. Percutaneous absorption through adult human foreskin was tested in flow-through diffusion cells using [3H]PGE1. Nine healthy volunteers participated in the crossover, randomized, double-blind, placebo-controlled study, where 0.1 g of each preparation was applied to a 4 cm2 area on the forearm. Laserflo BPM2 blood perfusion monitor with Model P-430 skin probe was used for evaluating skin blood perfusion. Encapsulation of PGE1 into novel biphasic delivery systems resulted in significantly increased skin blood perfusion relative to traditional liposomal, nonliposomal, and placebo formulations (6.25 +/- 1.58 vs 2.72 +/- 0.79, 0.53 +/- 0.64, and 0.58 +/- 0.06 mLLD/min/100 g, respectively, n = 9). The in vitro absorption of PGE1 through foreskin correlated well with the in vivo data (respective permeability coefficients 3.33, 1.57, and 1. 40 x 10(-4) cm/h). Formulation parameters greatly influence the absorption of PGE1 through skin as measured by laser doppler flowmetry, but by the application of a novel topical delivery technology, a significant enhancement of PGE1 delivery can be achieved.

Adult↗

PubMed1998

Differential regulation of endothelin-1 action by insulin and vanadate in vascular smooth muscle.

The effects of insulin (10 nM) and sodium orthovanadate (SOV, 25 microM) pretreatment for 24 h on endothelin-1 (ET-1) and IRL-1620 (ETB agonist)-evoked increases in intra-cellular free calcium levels [Ca2+]i were determined by fura-2 fluorescence methodology using cultured rat aortic smooth-muscle cells (ASMCs). Whereas insulin preincubation led to an increase (p < 0.05) in [Ca2+]i responses to ET-1, SOV enhanced [Ca2+]i responses to both ET-1 (p < 0.05) and IRL-1620 (p < 0.01). Saturation binding studies revealed that insulin pretreatment led to a 2.2-fold (p < 0.01) increase in [125I]ET-1 binding sites, and SOV pretreatment led to a 2.4-fold (p < 0.01) and 6.6-fold (p < 0.01) increase in the maximal number of binding sites labeled by [125I]ET-1 and [125I]IRL-1620, respectively. Northern blot analysis revealed that insulin upregulated only ETA mRNA levels, and SOV enhanced both ETA and ETB mRNA levels. Pretreatment with the tyrosine kinase inhibitor genistein abolished these effects. These data suggest that insulin pretreatment of ASMCs selectively upregulates ETA receptor expression and ETA-mediated [Ca2+]i, signaling, and SOV upregulates both ETA and ETB receptor expression and exaggerates [Ca2+]i responses mediated by both ETA and ETB in rat ASMCs.

Animals↗

PubMed1998

Nuclear Ca2+ signaling to endothelin-1 in rat aortic smooth-muscle cells.

Vascular smooth-muscle cells (VSMCs) isolated from genetically hypertensive animals show increased intracellular free calcium levels ([Ca2+]i) in response to endothelin-1 (ET-1). The differences in time course and distribution of Ca2+ increase after addition of ET-1 within the VSMCs are unknown. Therefore, ET-1-evoked changes in fluo-3 fluorescence were determined using a confocal laser scanning microscope in primary cultures of aortic smooth-muscle cells (ASMCs) from 12-week-old male Sprague-Dawley (SD) rats, Wistar-Kyoto (WKY) rats, and spontaneously hypertensive rats (SHR). Syto-11 staining enabled the assessment of intracellular free [Ca2+]i changes in the cytosolic ([Ca2+]c), perinuclear ([Ca2+]p), and nuclear ([Ca2+]n) regions. In the basal state, [Ca2+] was evenly distributed throughout the rat ASMCs. There were no significant differences in basal fluorescence values among the three strains. ET-1 evoked a concentration-dependent increase in fluo-3 intensity. The peak [Ca2+]i rise to ET-1 was much more rapid in ASMCs from SHR and WKY strains. The changes in [Ca2+]n were greater than in [Ca2+]c. Pretreatment of rat ASMCs with BQ-123 (an ETA antagonist) and BQ-788 (an ETB antagonist) abolished the rapid peak rise and the slow sustained elevation in [Ca2+]i, respectively. The nonselective antagonist bosentan attenuated both phases of the ET-1 response in all three strains. The ETB-selective agonist IRL 1620 evoked a significant elevation in [Ca2+]n values at 2 min in the ASMCs of SHR. These data suggest that ETA activation is linked to initial rapid increases in [Ca2+]c and [Ca2+]n, whereas ETB activation promotes slow [Ca2+]n signaling, particularly in ASMCs of SHR.

Aniline Compounds↗

PubMed1998

Effects of lipid-lowering agents in the Dahl salt-sensitive rat.

Inducing renal cytochrome P4504A (P4504A) activity with clofibrate prevents the development of hypertension in Dahl salt-sensitive (Dahl S) rats. To determine if this also occurs with other antilipidemic agents, we compared the effects of a related drug, fenofibrate, with those of an unrelated agent, pravastatin, on blood pressure, renal histology, and P4504A activity. Dahl S rats were pretreated with fenofibrate (95 mg/kg per day), pravastatin (70 mg/kg per day), or vehicle for 7 days before and after being switched from a low-salt (0.1% NaCl) to a high-salt (8.0% NaCl) diet. After 3 weeks on the high-salt diet, mean arterial pressures averaged 183+/-13 (n=9), 126+/-10 (n=9), and 148+/-11 mm Hg (n=8), respectively, in vehicle-, fenofibrate-, and pravastatin-treated animals. Both drugs reduced the degree of proteinuria and glomerular injury. P4504A protein levels and the synthesis of 20-hydroxyeicosa-5,8,11,14-tetraenoic acid (20-HETE) were increased in the liver and kidney of fenofibrate-treated, but not pravastatin-treated rats. We also administered these agents to Dahl S rats in which hypertension had previously been induced by a high-salt diet. Mean arterial pressures averaged 164+/-10, 113+/-23, and 160+/-15 mm Hg in rats treated with vehicle, fenofibrate, or pravastatin for 3 weeks. Fenofibrate-treated rats exhibited a natriuresis. Proteinuria and glomerular injury were reduced by pravastatin but not by fenofibrate. These results indicate that fenofibrate prevented the development of hypertension and reduced subsequent glomerular injury in Dahl S rats, probably secondary to increased renal production of 20-HETE. Although pravastatin did not induce renal P4504A activity in these animals, it reduced the severity of hypertension and renal damage through some other mechanism.

Animals↗

PubMed1998

Effects of ridogrel, a thromboxane synthase inhibitor and receptor antagonist, on blood pressure in the spontaneously hypertensive rat.

Ridogrel is a dual acting thromboxane synthase inhibitor/TP receptor antagonist. We examined the effects of single and multiple doses on systolic blood pressure in stroke-prone spontaneously hypertensive rats. Single doses of ridogrel (5 to 125 mg/kg) did not affect systolic blood pressure or furosemide-stimulated excretion rates of thromboxane B2 or 6-keto-prostaglandin F1alpha, although ex vivo serum thromboxane B2 was dose-dependently reduced up to 95%. In contrast, repeated dosing (7 days) with ridogrel (3 to 25 mg/kg/day), had an antihypertensive effect in 12-week-old stroke-prone spontaneously hypertensive rats. At 25 mg/kg/day, ridogrel reduced systolic blood pressure from 200+/-6.1 to 173+/-6.7 mmHg (n=12, P<0.01). Ridogrel dose-dependently reduced serum thromboxane B2 and increased plasma renin activity. Unlike single doses, repeated dosing reduced urinary thromboxane B2 excretion (from 103+/-7 ng/day to 49+/-10 ng/day, P<0.01) while preserving 6-keto-prostaglandin F1alpha excretion. Ketoprofen, a cyclo-oxygenase inhibitor, (10 mg/kg/day for 7 days), depressed urine 6-keto-prostaglandin F1alpha in addition to attenuating serum and urine thromboxane B2. Ketoprofen prevented the antihypertensive effects of ridogrel. Ridogrel did not lower systolic blood pressure in Sprague-Dawley rats. We conclude that the antihypertensive effect of ridogrel involves preserving renal prostaglandin synthesis during thromboxane attenuation.

6-Ketoprostaglandin F1 alpha↗

PubMed1998

Insulin increases endothelin-1-evoked intracellular free calcium responses by increased ET(A) receptor expression in rat aortic smooth muscle cells.

While insulin is known to promote vascular smooth muscle (VSM) relaxation, it also enhances endothelin-1 (ET-1) secretion and action in conditions such as NIDDM and hypertension. We examined the effect of insulin pretreatment on intracellular free calcium ([Ca2+]i) responses to ET-1 in cultured aortic smooth muscle cells (ASMCs) isolated from Sprague-Dawley (SD) rats and measured ET(A) receptor characteristics and ET-1-evoked tension responses in aorta obtained from insulin-resistant, hyperinsulinemic Zucker-obese (ZO) and control Zucker-lean (ZL) rats. Pretreatment of rat ASMCs with insulin (10 nmol/l for 24 h) failed to affect basal [Ca2+]i levels but led to a significant increase in peak [Ca2+]i response (1.7-fold; P < 0.01) to ET-1. The responses to IRL-1620 (an ET(B) selective agonist), ANG II, and vasopressin remained unaffected. ET-1-evoked peak [Ca2+]i responses were significantly attenuated by the inclusion of the ET(A) antagonist, BQ123, in both groups. The ET(B) antagonist, BQ788, abolished [Ca2+]i responses to IRL-1620 but failed to affect the exaggerated [Ca2+]i responses to ET-1. Saturation binding studies revealed a twofold increase (P < 0.01) in maximal number of binding sites labeled by 125I-labeled ET-1 in insulin-pretreated cells and no significant differences in sites labeled by 125I-labeled IRL-1620 between control and treatment groups. Northern blot analysis revealed an increase in ET(A) mRNA levels after insulin pretreatment for 20 h, an effect that was blocked by genistein, actinomycin D, and cycloheximide. Maximal tension development to ET-1 was significantly greater (P < 0.01), and microsomal binding studies using [3H]BQ-123 revealed a twofold higher number of ET(A) specific binding sites (P < 0.01) in aorta from ZO rats compared with that of ZL rats. These data suggest that insulin exaggerates ET-1-evoked peak [Ca2+]i responses via increased vascular ET(A) receptor expression, which may contribute to enhanced vasoconstriction observed in hyperinsulinemic states.

Animals↗

PubMed1997

Renal P450 metabolites of arachidonic acid and the development of hypertension in Dahl salt-sensitive rats.

Renal transplantation studies indicate that some form of renal dysfunction underlies the development of hypertension in Dahl salt-sensitive (S) rats; however, the factors responsible for altering kidney function remain to be determined. Previous studies have indicated that Dahl S rats require a higher renal perfusion pressure to excrete the same amount of sodium and water as normotensive rats and that this is due largely to an elevation in Cl- transport in the thick ascending limb of the loop of Henle. There are now five lines of evidence that suggest an abnormality in the renal metabolism of arachidonic acid by enzymes of the P4504A family may contribute to the increase in loop Cl- transport and the development of hypertension in Dahl S rats. In this regard, the formation of 20-HETE and the levels of P4504A protein are reduced in the outer medulla of Dahl S rats. Perfusion of the loop of Henle of Dahl S rats with exogenous 20-HETE normalizes the elevated loop Cl- transport. In addition, a genetic marker in the P4504A2 gene, which encodes for the enzyme that makes 20-HETE, cosegregates with the development of hypertension in an F2 cross of Dahl S and Lewis rats. Finally, induction of renal production of 20-HETE with clofibrate prevents the development of hypertension in Dahl S rats and inhibition of renal 20-HETE formation produces hypertension in Lewis rats fed a high salt diet. These results implicate the CYP4A2 locus as a candidate gene that contributes to the alterations in renal function and the development of hypertension in Dahl S rats.

Animals↗

PubMed1997

Losartan: a new antihypertensive drug.

Hypertension is a major risk factor for cardiovascular disease. It affects approximately one in five, or 20 per cent of Canadians. The consequences of untreated hypertension include myocardial infarction, stroke, congestive heart failure, peripheral vascular disease and renal disease. By lowering a person's diastolic blood pressure 5 to 6 mmHg, their chances of having a stroke are reduced by 35 to 40 per cent and 20 to 25 per cent for coronary heart disease. While the treatment for hypertension includes both nonpharmacological and pharmacological therapy, this article will explore losartan or Cozaar, which falls under the newest class of antihypertensive drugs, angiotensin II antagonists.

Angiotensin II↗

PubMed1997

Patterns of compliance with once versus twice daily antihypertensive drug therapy in primary care: a randomized clinical trial using electronic monitoring.

OBJECTIVE: To evaluate patterns of compliance with once versus twice daily administration of antihypertensive therapy (primary-outcome measure) and relevance of partial compliance for blood pressure control (secondary outcome measure). DESIGN: Multicentre, nonblinded, parallel group randomized design. SETTING: Nonacademic primary care practices across Canada. STUDY POPULATION: Patients with mild essential hypertension (diastolic blood pressure 95 to 110 mmHg) of either sex (40% women), age 18 to 80 years (average 55 years). One hundred and ninety-eight patients were randomized to active treatment; 14 patients discontinued the study because of side effects. INTERVENTIONS: After a four-week placebo run-in period, patients were randomized to amlodipine 5 mg once-a-day or diltiazem slow release formulation (SR) 90 mg twice daily. Doses were increased to 10 mg and 180 mg to achieve sitting diastolic blood pressure of 90 mmHg or less. OUTCOME MEASURE: During 20 weeks on active treatment, compliance was assessed by pill counts and medication event monitoring system (MEMS), assessing percentage of prescribed doses taken, percentage days correct doses taken, percentage prescribed doses taken on time and blood pressure control as determined by office blood pressure measurement. RESULTS: The percentage prescribed doses taken (by either pill count of MEMS) showed a high degree of compliance, similar for the two treatments. However, other parameters of compliance were significantly better with once versus twice daily therapy. Partial compliance (less than 80% by pill count) led to less blood pressure control with the short acting diltiazem, but did not affect blood pressure control for the long acting amlodipine. Side effects profiles did not differ between the two treatments. CONCLUSIONS: Within the constraints of a clinical trial, hypertensive patients in primary care show a high degree of overall compliance with once or twice daily pill-taking, but patterns of pill-taking are more erratic with twice versus once daily medication, particularly in men. The results suggest that the negative consequences of partial compliance for blood pressure control can be offset by choosing agents with a duration of action well beyond the dosing interval.

Adolescent↗

PubMed1996

Penetration of chemotherapy into vitreous is increased by cryotherapy and cyclosporine in rabbits.

OBJECTIVE: To investigate whether cryotherapy, which induces a serous effusion in retina, might increase access of systemic chemotherapy into the vitreous. METHODS: The right eyes of 18 rabbits were treated with triple or single freeze-thaw cryotherapy at 1 or 2 locations, 1 day before administering intravenous carboplatin with or without cyclosporine. Control left eyes received no cryotherapy. The rabbits were killed 2 or 24 hours after chemotherapy, and carboplatin concentrations were measured in the vitreous of each eye and in blood. RESULTS: A significant increase was found in intravitreal carboplatin concentrations when cryotherapy was applied (P < .001) or high-dose cyclosporine was administered (P < .001) and if 2 locations were frozen compared with 1 location frozen (P = .02). Intravitreal carboplatin concentrations were always significantly greater after cryotherapy, either when the corresponding blood carboplatin concentrations were high (2 hours after completing treatment) or when they had dropped to much lower levels (at 24 hours). The triple freeze-thaw technique did not yield significantly better results than a single freeze-thaw technique. CONCLUSION: Cryotherapy administered 24 hours before chemotherapy significantly increased the intravitreal penetration of carboplatin, and this strategy may enhance the capacity of chemotherapy to cure intraocular retinoblastoma, particularly avascular tumors such as vitreous seeds.

Animals↗

PubMed1996

Angle closure glaucoma complicating systemic atropine use in the cardiac catheterization laboratory.

Atropine may precipitate angle closure glaucoma in those predisposed to the disorder. Previously reported cases demonstrate the frequent misdiagnosis of acute glaucoma as conjunctivitis. Resultant delays in treatment can lead to vision loss. The present case describes a 66-yr-old man who developed acute angle closure glaucoma after receiving atropine during a coronary angioplasty produce. Clinicians who utilize atropine should be aware of the possibility of precipitating angle closure glaucoma and the predisposing factors, signs, and symptoms to facilitate prompt diagnosis and treatment of this disorder.

Aged↗

PubMed1996

Effect of an endothelin antagonist on hemodynamic responses to angiotensin II.

We determined changes in blood pressure, cardiac output, and total peripheral conductance evoked by intravenous infusions of angiotensin II (Ang II) in conscious, unrestrained normotensive Wistar-Kyoto rats (WKY) and spontaneously hypertensive rats (SHR) before and after pretreatment with bosentan, a nonselective endothelin antagonist. Blood pressure was recorded by radiotelemetry and cardiac output by ultrasonic transit-time flow probes. Bosentan per se failed to affect basal blood pressure and evoked only small changes in cardiac output and total peripheral conductance in both strains. The pressor effects of Ang II were exaggerated in SHR compared with WKY. Strikingly, bosentan pretreatment blunted the increases in blood pressure, the fall in cardiac output, and the decreases in conductance evoked by lower doses of Ang II but not higher doses of the peptide. This effect was observed in both rat strains but was more pronounced in SHR. These data suggest that endothelin contributes to the hemodynamic effects of Ang II in both SHR and WKY and that endothelin may contribute to the exaggerated pressor responsiveness of SHR to Ang II.

Angiotensin II↗

PubMed1996

Pharmacoeconomics of hypertension control: basic principles of economic evaluation.

Pharmacoeconomics, the science of assigning costs and outcomes of drug therapy can be applied to antihypertensive drug therapy. There are five principle tools: cost identification, cost minimization, cost benefit, cost effectiveness and cost utility. If only drug aquisition costs are considered, there are marked differences among antihypertensive drug classes. These differences become less marked when the costs per quality adjusted life year are calculated. Often, differences among patients rather than differences among drug prices account for the bulk of variation.

Adult↗

PubMed1995

Differential effects of phosphoramidon on contractile responses to angiotensin II in rat blood vessels.

1. Cumulative concentration-tension response (C-R) curves to angiotensin II (AII), big endothelin-1 (big ET-1), ET-1 and arginine vasopressin (AVP) were determined in endothelium intact-ring preparations of aorta, mesenteric artery and tail artery isolated from adult male Sprague-Dawley rats in the presence or absence of the neutral metalloprotease inhibitor, phosphoramidon. 2. The order of sensitivity of the three rat vascular smooth muscle preparations to AII, big ET-1 and ET-1 was aorta > mesenteric artery > tail artery whereas that for AVP was reversed, namely, tail artery > mesenteric artery > aorta. 3. Phosphoramidon blocked the responses to AII in a concentration-dependent manner, whereas even very high concentrations of phosphoramidon (100 microM) failed to affect the tension responses evoked by ET-1 and AVP in all three preparations. Low concentrations of phosphoramidon (10 microM) produced significant increases in EC50 values for AII in tail artery (P < 0.01) and mesenteric artery (P < 0.05) but not in aorta. The rank order of sensitivity to the inhibition by phosphoramidon was tail artery > mesenteric artery > aorta. Phosphoramidon-evoked rightward shifts in the C-R curves to AII were much higher than those to big ET-1 in both mesenteric artery and tail artery. 4. In endothelium-denuded preparations, AII failed to evoke any increases in tension in tail artery while the responsiveness of the mesenteric artery to AII was reduced significantly relative to endothelium-intact tissues with a rightward shift in the C-R curve and a decrease in the maximal response. On the other hand, the C-R curve to AII was shifted to the left in aorta following removal of the endothelium.Importantly, ET-1 and AVP evoked vasoconstrictor responses were unaffected by the inclusion of a high concentration of phosphoramidon (100 microM) in endothelium-denuded aorta and mesenteric artery.5. The results suggest that AII-evoked tension responses of blood vessels such as tail artery are completely endothelium-dependent; in relatively larger blood vessels such as mesenteric artery they are partially endothelium-dependent while in much bigger conduit type blood vessel such as aorta, they are endothelium-independent. It is concluded that the vasoconstrictor responses to AII in mesenteric artery and tail artery may be mediated by the release of endothelins from the endothelium by increased formation from big ET, an effect that is blocked by phosphoramidon.

Angiotensin II↗

PubMed1995

Heterogeneity in vascular smooth muscle responsiveness to angiotensin II. Role of endothelin.

We compared the role of endothelium and of endothelin in mediating the vasoconstrictor responses to angiotensin II (Ang II) in three vascular smooth muscle preparations--aorta, mesenteric artery, and tail artery--isolated from adult male Sprague-Dawley rats. The vasoconstrictor potency for Ang II in blood vessels with endothelium varied in the following rank order: aorta > mesenteric artery > tail artery. Although the maximal tension responses to Ang II were similar for mesenteric and tail arteries, it was significantly lower in aorta. Endothelium removal led to a leftward shift in the concentration-response curves to Ang II in the aorta but a rightward shift in the mesenteric artery. Strikingly, Ang II failed to evoke tension responses in tail artery in the absence of endothelium. The endothelin-A (ETA)-selective antagonist BQ-123 blocked the responses to Ang II in a noncompetitive manner, with partial and complete attenuation of responses in the endothelium-intact mesenteric and tail artery preparations, respectively. In contrast, BQ-123 did not affect the responses to Ang II in the aorta. BQ-123 also failed to affect the responses to Ang II in endothelium-denuded mesenteric artery rings. The Ang II type 1 (AT1) receptor-selective antagonist losartan competitively blocked the responses to Ang II in the three tissues (pA2, 8.3 to 8.7) when endothelium was present. These data suggest that there are endothelium-dependent regional variations in vascular tissue sensitivity to Ang II.(ABSTRACT TRUNCATED AT 250 WORDS)

Angiotensin II↗

PubMed1995

Is the relationship between supine blood pressure and postural changes in blood pressure artefactual? Results from the Kuopio Ischemic Heart Disease Risk Factor Study.

OBJECTIVE: To investigate whether there is an association between initial supine blood pressure and postural changes in blood pressure (standing minus supine blood pressure). METHODS: Using data from the Kuopio (Finland) Ischemic Heart Disease Risk Factor Study (KIHD), we simulated the problem and found the suggested solution based on the work of Blomqvist. We then applied the Blomqvist correction to the KIHD data with real measurement errors. RESULTS: The observed regression slope was substantially reduced, indicating that there is no relationship between the initial blood pressure and the postural change in blood pressure. CONCLUSION: Only the broad application of the method of Blomqvist to other data sets will determine the generalizability of the present finding that initial blood pressure is unrelated to the postural change in blood pressure.

Adult↗

PubMed1995

Comparative pharmacology of calcium antagonists.

OBJECTIVE: To compare clinically relevant pharmacokinetic, pharmacodynamic and toxico logical characteristics of calcium-modulating compounds used in ischemic heart disease. DATA SOURCES: A MEDLINE search (1990 pt B to 1991 pt A revised for 1993; 1991 pt B to 1992 revised for 1993; and January to May 1993) combining the search phrases 'calcium channel blockers', 'myocardial ischemia', 'pharmacodynamics' and 'pharmacokinetics', and a search in Compact Cambridge Drug Information Source vol-6 (revised 1992, fourth quarter) using the search phrase 'calcium antagonists' and medical subject headings (MeSH) 'pharmacokinetics' and 'pharmacodynamics' were used to obtain title and abstract information on available current literature. STUDY SELECTION: Review articles, proceedings and studies published in English and available within the University of Saskatchewan library system, as they appeared to relate closely to the objective, were obtained for closer evaluation. In addition, primary references were examined, and journal reprints were selected from the authors' files. DATA EXTRACTION: The focus was on studies and objective reviews that profiled one or more representative compounds in a manner suitable for deriving background and comparative information pertaining to the objective. Data from multiple studies, or from studies that employed multiple methodological approaches, were preferentially extracted and summarized for presentation. DATA SYNTHESIS: The role of calcium in cardiac and vascular smooth muscle physiology was reviewed, highlighting the major mechanisms responsible for maintaining calcium homeostasis in these cells. With a focus on verapamil, diltiazem and 1,4-dihydropyridines currently employed in the treatment of cardiovascular disorders, a general survey of their sites of action, tissue selective pharmacodynamics, pharmacokinetic properties and side effects was undertaken in a comparative context. CONCLUSIONS: Calcium antagonists are employed in the treatment of angina, certain cardiac arrhythmias and hypertension. They are a chemically and pharmacologically heterogeneous group of compounds that act principally to inhibit the influx of calcium across certain voltage-dependent membrane channels. Concepts pertaining to calcium mobilization in the pathophysiology of myocardial ischemia, particularly at the molecular level, have evolved remarkably over the past decade. The repertoire of agents having calcium-regulating properties has expanded in parallel. The task of integrating new knowledge in both of these areas requires further attention in order to determine optimal approaches to treatment.

Animals↗

PubMed1994

Childhood and adult socioeconomic status as predictors of mortality in Finland.

Research has suggested that social-class differences in adult health may be at least partly determined by conditions earlier in life. In 2636 Finnish men, we assessed impact of childhood and adult socioeconomic conditions on adult mortality risk by examining whether differing socioeconomic life-courses from early childhood to adulthood were associated with different risks of all-cause and cardiovascular mortality. Compared with high-income adults, those with low income had increased relative risks of all-cause (2.54, 95% CI 1.83-3.53) and cardiovascular (2.37, 1.51-3.7) mortality, but these increased risks were not related in either adult group to childhood socioeconomic conditions. Men who went from low-income childhood to high-income adulthood had the same mortality risks as those whose socioeconomic circumstances were good in both childhood and adulthood (1.14, 0.56-2.31, all causes; 0.99, 0.39-2.51, cardiovascular). By contrast, men who experienced poor socioeconomic circumstances as both children and adults were about twice as likely to die as those whose position improved (2.39, 1.28-4.44, all causes; 2.02, 0.9-4.54, cardiovascular). Our findings suggest that socioeconomic conditions in childhood are not important determinants of adult health. We caution against this interpretation--a life-course approach to socioeconomic differences in adult health requires understanding of the social and economic context in which individual life-courses are determined.

Adult↗