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A Heagerty

Publications and source records attributed to A Heagerty.

13 recordsLinked to original sources
PubMed1996

Susceptibility to multiple cutaneous basal cell carcinomas: significant interactions between glutathione S-transferase GSTM1 genotypes, skin type and male gender.

The factors that determine development of single and multiple primary cutaneous basal cell carcinomas (BCCs) are unclear. We describe a case-control study firstly, to examine the influence of allelism at the glutathione S-transferase GSTM1 and GSTT1 and cytochrome P450 CYP2D6 loci on susceptibility to these tumours and, secondly, to identify interactions between genotypes and relevant individual characteristics, such as skin type and gender. Frequency distributions for GSTM1 genotypes in cases and controls were not different, although the frequency of GSTM1 A/B was significantly lower (P = 0.048) in the multiple BCCs than in controls. We found no significant differences in the frequencies of GSTT1 and CYP2D6 genotypes in cases and controls. Interactions between genotypes were studied by comparing multinomial frequency distributions in mutually exclusive groups. These identified no differences between cases and controls for combinations of the putatively high risk GSTM1 null, GSTT1 null, CYP2D6 EM genotypes. Interactions between GSTM1 A/B and the CYP2D6 PM and GSTT1-positive genotypes were also not different. Frequency distributions of GSTM1 A/B with CYP2D6 EM in controls and multiple BCCs were significantly different (P = 0.033). The proportion of males in the multiple BCC group (61.3%) was greater than in controls (47.0%) and single BCC (52.2%), and the frequency of the combination GSTM1 null/male gender was significantly greater in patients with multiple tumours (P = 0.002). Frequency distributions of GSTM1 null/skin type 1 were also significantly different (P = 0.029) and the proportion of subjects who were GSTM1 null with skin type 1 was greater (P = 0.009) in the multiple BCC group. We examined the data for interactions between GSTM1 null/skin type 1/male gender by comparing frequency distributions of these factors in the single and multiple BCC groups. The distributions were almost significantly different (exact P = 0.051). No significant interactions between GSTT1 null or CYP2D6 EM and skin type 1 were identified. Comparisons of frequency distributions of smoking with the GSTM1 null, GSTT1 null and CYP2D6 EM genotypes identified no differences between patients with single and multiple tumours.

Aged↗
PubMed1994

Small arteries and hypertension.

AIM: To review current knowledge on the behaviour of small arteries in hypertension and when the blood pressure is lowered. METHOD: Literature review. CONCLUSIONS: The evidence available at present suggests that despite normalization of blood pressure, the flow reserve in small coronary arteries is not necessarily restored to normal. Therefore the risk of cardiac ischaemia may remain and this may explain the current failure to reduce all cardiac risk associated with hypertension despite effective antihypertensive treatment.

Animals↗
PubMed1993

Regulation of diacylglycerol metabolism by vasoconstrictor hormones in intact small arteries.

The initiation of receptor-mediated small artery contraction is dependent on inositol 1,4,5-trisphosphate-stimulated release of stored calcium. The role of the other product of inositol lipid hydrolysis, 1,2-diacylglycerol, in maintaining contraction remains controversial. Therefore, we have determined the contractile response of rat subcutaneous small arteries (< 300 microns i.d.), when mounted as ring preparations in a myograph, to noradrenaline, angiotensin II, KCl-induced membrane depolarization, and a cell-permeable diglyceride, dioctanoylglycerol. In parallel experiments, the conversion of this diglyceride to dioctanoylphosphatidate was studied in 32P-labeled vessels. Dioctanoylglycerol produced a slow-onset sustained contraction that was dependent on extracellular calcium. This was accompanied by the generation of the lipid dioctanoylphosphatidate. Noradrenaline and KCl induced rapid-onset sustained contractions and increased the production of dioctanoylphosphatidate (75% and 91%, respectively). In addition, dioctanoylglycerol levels were reduced (41%) after noradrenaline stimulation, suggesting activation of diacylglycerol kinase. In contrast, the contractile response to angiotensin II was transient, and this agonist did not significantly affect the conversion of dioctanoylglycerol to phosphatidate. Noradrenaline markedly increased (fourfold) the formation of endogenous phosphatidate, whereas endogenous 1,2-diacylglycerol was increased (47%) with angiotensin II. These results demonstrate that phosphatidate formation is regulated by vasoconstrictor hormones during receptor-mediated contraction, independent of diglyceride mass. Modulation of the levels of lipid second messengers downstream from phospholipid hydrolysis may represent a mechanism by which agonists that act through the same signaling system produce different contractile responses.

Angiotensin II↗
PubMed1992

Familial Conn's syndrome.

We describe the occurrence of primary hyperaldosteronism in two sisters. Although this is only the second published report of familial Conn's syndrome, it does have implications for the relatives of patients with Conn's syndrome and these are discussed.

Adenoma↗
PubMed1991

Lip dermatoses.

Explore the source record for details and available documents.

Adolescent↗
PubMed1990

Agonist-induced production of 1,2-diacylglycerol and phosphatidic acid in intact resistance arteries. Evidence that accumulation of diacylglycerol is not a prerequisite for contraction.

The production of total amounts of 1,2-diacylglycerol as well as those specifically derived from inositol lipid hydrolysis was studied in intact rat resistance arteries stimulated with either noradrenaline, vasopressin, or angiotensin II at 20 s when the onset of contraction would be nearing its maximum, and at 5 min during the sustained phase of contraction. Total amounts of 1,2-diacylglycerol were not altered by any agonist at 20 s, or at 5 min. However, arachidonate-containing species of 1,2-diacylglycerol were differentially influenced being increased at 5 min by noradrenaline, and decreased at 20 s and 5 min by vasopressin. Only angiotensin II produced substantial increases in this class of 1,2-diacylglycerol at both time points. In order to investigate the fate of this second messenger total and inositol lipid derived phosphatidic acids were then measured at both 20 s and 5 min. Noradrenaline induced a rise in both total and arachidonate-containing phosphatidic acid at both times as did vasopressin. Only small increases were induced by angiotensin II at 20 s. These data demonstrate that the accumulation of 1,2-diacylglycerol generated from inositol lipid breakdown is only observed with activation by angiotensin II. Other agonists produced phosphatidic acids with time and the rate of generation of these lipids is agonist-specific. Thus phosphatidic acid may play a more prominent role during the sustained phase of contraction than previously anticipated.

Angiotensin II↗
PubMed1989

Amoxycillin/clavulanic acid (Augmentin)-induced intrahepatic cholestasis.

A 75-year-old man developed a biopsy-proven, drug-induced intrahepatic cholestasis after use of amoxycillin trihydrate combined with the beta-lactam inhibitor potassium clavulanate (Augmentin). Cholestatic liver injury is an uncommonly recognized, probably immunologically based adverse reaction to therapy with penicillin and its derivatives.

Aged↗
PubMed1983

Improvement of renal function during long-term treatment of severe hypertension with minoxidil.

Sixty-nine patients with refractory hypertension were treated with minoxidil and in 66 good control of blood pressure was achieved. Renal function was stabilized in 31 patients in whom the serum creatinine was normal at presentation. Twenty-eight patients with impaired renal function had a substantial fall in serum creatinine (25 per cent) during the first three to six months of treatment and this improvement was maintained. In contrast, renal function in six out of seven patients with primary renal disease continued to deteriorate despite adequate control of blood pressure. Effective control of blood pressure prevents or reverses impairment of renal function in patients with refractory hypertension not associated with primary renal disease.

Blood Pressure↗
PubMed1982

Treatment of refractory hypertension.

126 patients with blood pressure which was unacceptably high despite a conventional stepped-care regimen (diuretic, beta-blocker, and vasodilator) took part in a comparative assessment of different approaches to the treatment of refractory hypertension. One of four regimens was used: oral diazoxide, minoxidil, captopril, or quadruple therapy (diuretic + beta-adrenoceptor blocker + hydralazine + prazosin). Despite the severity of hypertension, blood pressure could be controlled in almost all these patients, and no patient died from cerebrovascular disease while on treatment. 2 patients died of renal failure and 5 patients required long-term haemodialysis. Ischaemic heart disease remained a problem and caused the death of 10 patients. Diazoxide was the most effective treatment but was the most difficult and unpleasant to use. Captopril was the best-tolerated but failed to control blood pressure in 6 of 15 patients. Our experience indicates that there are now sufficient therapeutic alternatives to achieve acceptable blood-pressure control in almost all patients with "refractory" hypertension, although no treatment is ideal.

Adrenergic beta-Antagonists↗