Biomedical subjects
Publications and source records attributed to B McGrath.
One of the defining characteristics of general practice is its heterogeneity. GPs vary widely in their assessment and management of clinical problems. It is therefore likely that this environment will generate numerous questions that require the use of various research approaches. This paper discusses how to choose between these approaches.
OBJECTIVES: This study investigated the effects of hormonal therapy on large arterial properties. BACKGROUND: Arterial stiffness is an emerging risk marker for coronary heart disease and is potentially modifiable. Postmenopausal use of hormonal therapy is associated with a lower risk of coronary heart disease. METHODS: Total systemic arterial compliance (SAC) and pulse wave velocity (PWV) were determined in 26 premenopausal and 52 postmenopausal women, 26 of whom were taking hormonal therapy. RESULTS: Arterial compliance was greater in the premenopausal group (mean +/- SEM 0.57 +/- 0.04 arbitrary compliance units [ACU]) than in the postmenopausal group not taking hormonal therapy (0.26 +/- 0.02 ACU, p = 0.001). Postmenopausal women taking hormonal therapy had a significantly increased total SAC compared with women not taking hormonal therapy (0.43 +/- 0.02 vs. 0.26 +/- 0.02 ACU, p = 0.001). PWV in the aortofemoral region in the premenopausal women was 6.0 +/- 0.2 vs. 8.9 +/- 0.3 m/s (p < 0.001) in untreated postmenopausal women. However, postmenopausal women taking hormonal therapy had a significantly lower PWV than those not taking hormonal therapy (7.9 +/- 0.2 vs. 8.9 +/- 0.3 m/s, p = 0.01). Eleven postmenopausal women had their hormone replacement therapy withdrawn for 4 weeks, resulting in a significant decrease in SAC and a significant increase in aortofemoral PWV. CONCLUSIONS: The increased SAC and decreased PWV in women receiving hormonal therapy suggest that such therapy may decrease stiffness of the aorta and large arteries in postmenopausal women, with potential benefit for age-related cardiovascular disorders. The reduction of arterial compliance with age appears to be altered with hormonal therapy.
OBJECTIVES: To measure the effect of continuous venovenous hemofiltration with dialysis on cardiovascular stability in the critically ill patients and to assess the extraction of a number of hormones and catecholamines by continuous venovenous hemofiltration with dialysis. DESIGN: Prospective, clinical study. SETTING: Intensive care unit of a tertiary medical center. PATIENTS: Twenty critically ill patients with acute renal failure. INTERVENTIONS: Timed collections of serum and ultradiafiltrate in patients receiving continuous venovenous hemofiltration with dialysis, with measurements of their catecholamine and hormonal content and calculation of continuous venovenous hemofiltration with dialysis clearances and daily extractions. Correlation of changes in catecholamines with prospectively collected hemodynamic data during the first 24 hrs of continuous venovenous hemofiltration with dialysis therapy. MEASUREMENTS AND MAIN RESULTS: No significant changes in dopamine, epinephrine, and norepinephrine requirements or plasma concentrations were seen during the first 24 hrs of continuous venovenous hemofiltration with dialysis. Overall daily losses of catecholamines in the ultradiafiltrate were small (dopamine 404 micrograms; epinephrine 32 micrograms; norepinephrine 29 micrograms). Hemodynamic variables remained stable during this period of continuous venovenous hemofiltration with dialysis therapy. All studied hormones were detected in the ultradiafiltrate, but their mean daily extractions were very small (aldosterone 0.37 micrograms; parathyroid hormone 53.4 pmol; cortisol 4.8 mg; T4 and T3 [trace amounts]; thyroid-stimulating hormone 2.6 mU; testosterone [trace amounts]). CONCLUSIONS: In critically ill patients with acute renal failure, continuous venovenous hemofiltration with dialysis results in minimal losses of catecholamines and is associated with cardiovascular stability. It causes only minor losses of several hormones. These losses are unlikely to be clinically important. Thus, blood purification achieved by continuous venovenous hemofiltration with dialysis does not produce significant catecholamine or hormonal losses and is associated with hemodynamic stability.
Although lisinopril and enalapril are equipotent angiotensin converting enzyme (ACE) inhibitors lisinopril has been reported to produce greater inhibition of plasma ACE 24 hours after single doses. This study compared the antihypertensive effects of once daily 10mg doses of the drugs using a randomised, double-blind, two period cross-over design with ambulatory blood pressure monitoring. Lisinopril lowered mean 24 hour systolic blood pressure significantly more than enalapril after 4 weeks of treatment (14/7 +/- 2/1mmHg & 9/6 +/- 2/1mmHg, respectively, adjusted SBP difference 4.8mmHg, P < 0.01). This difference was confined to the second 12 hours of the daily dosage interval (adjusted SBP difference 13-24 hours after dosing 9.9mmHg, P < 0.001). The diastolic pressure showed a similar trend but this was not statistically significant. The side effects of each agent were minor. We conclude that chronic, once daily therapy with 10mg of lisinopril reduces systolic blood pressure more effectively than an equal dose of enalapril due to its greater effect in the latter half of the 24 hour dosage interval.
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1. The effects of graded treadmill exercise on renal blood flow (RBF) were examined in seven rabbits, in which congestive heart failure (CHF) was produced by the administration of doxorubicin, 1 mg/kg, twice weekly for 8 weeks, and in seven controls. A third group of five rabbits underwent doxorubicin treatment with the addition of surgical section of the left renal sympathetic nerve. 2. During submaximal exercise, there was a small reduction in RBF in controls, which was greatly exaggerated in CHF. 3. In both control and heart failure rabbits, there was a precipitous fall in RBF as exercise fatigue developed. 4. Renal sympathectomy ablated these changes in RBF during exercise. 5. It is concluded that in heart failure there is an exaggerated, sympathetically mediated, diversion of blood flow away from the kidney. The onset of exercise fatigue in both normal and heart failure rabbits is accompanied by a marked intensification of this process.
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.
Felodipine was compared with prazosin in patients with essential hypertension whose blood pressure was not controlled by a beta-blocking drug. One hundred patients with a supine diastolic blood pressure greater than or equal to mm Hg after 4 weeks or more on a beta-blocking drug and placebo were randomly assigned to felodipine or prazosin tablets. The drugs were titrated at 2-week intervals if diastolic BP was greater than or equal to 90 mm Hg. Titration steps of felodipine were 5, 10, 20 mg b.i.d. and of prazosin were 1, 2, 4 mg b.i.d. The fall in blood pressure with felodipine 32/21 mm Hg was greater than the fall with prazosin 16/12 mm Hg (p less than 0.001); 36 patients achieved a diastolic blood pressure of less than 90 mm Hg with felodipine, which was a significantly greater number than the 20 patients who obtained such a level with prazosin (p less than 0.01). Both drugs were well tolerated, but more patients complained of vascular type side effects (flushing, peripheral edema) with felodipine than with prazosin. There was significant weight gain with prazosin but not with felodipine. Felodipine was shown to be a well-tolerated, effective antihypertensive agent when used with a beta-blocking drug and to be suitable for people with hypertension who fail to be controlled with a beta-blocking drug.
The in vivo cardiovascular effect of intravenous administration of monophosphoryl lipid A (mp-lipid A) and diphosphoryl lipid A (dp-lipid A) in awake New Zealand white rabbits was investigated. Observed changes were evaluated in comparison to a control group and an endotoxin-treated group. Rabbits given lipid A showed a significant depression in cardiac index (p less than .025), mean arterial pressure (p less than .025, dp-lipid A only), arterial carbon dioxide tension (p less than .025), and total leukocyte count (p less than .05) compared to controls. Animals receiving lipid A tended to respond overall in a manner closely matching that of the endotoxin group. Dosages of lipid A given were approximately 3.5 times larger than the endotoxin dosages with respect to actual number of molecules administered (1.25-2.0 times larger by mass). These results indicate that lipid A is active in producing the cardiovascular and leukopenic effects characteristic of experimental septic shock.
The effects of intravenous conscious sedation and general anesthesia on a number of stress variables were compared in healthy patients undergoing oral surgery. In the intravenous sedation group only the levels of plasma growth hormone and prolactin rose significantly. In the general anesthesia group significant rises were seen in heart rate; systolic blood pressure; mean arterial pressure; levels of plasma adrenaline, adrenocorticotropic hormone, cortisol, and prolactin; and levels of blood glucose, all indicative of a stress response. This study demonstrates that oral surgery under intravenous conscious sedation with local analgesia is associated with less patient stress than is oral surgery under general anesthesia.
The hemodynamic and hormonal changes produced by adriamycin-induced cardiomyopathic congestive heart failure in rabbits were studied. Adriamycin cardiomyopathy in rabbits led to ventricular dilatation, pleural and pericardial effusions, hepatic congestion, and ascites. These pathological changes were associated with the maintenance of a normal blood pressure but a lowered cardiac output and increased total peripheral resistance. Plasma renin activity and plasma norepinephrine were increased twofold in rabbits with congestive cardiac failure. However, plasma vasopressin and osmolality were normal, whereas an increased vascular sensitivity to the infusion of exogenous vasopressin was demonstrated. Despite the normal levels of plasma vasopressin, administration of a specific vascular vasopressin antagonist led to a fall in blood pressure, a significant increase in cardiac output, and a decrease in total peripheral resistance. No such hemodynamic changes occurred on infusing normal rabbits with the vascular vasopressin antagonist, nor did any significant hemodynamic changes occur on injecting vehicle in rabbits with heart failure. These results suggest that in adriamycin-induced cardiomyopathic heart failure in rabbits, there is activation of the renin-angiotensin system and the sympathetic nervous system together with an increased sensitivity to vasopressin. These three hormonal systems help to maintain blood pressure by increasing total peripheral resistance in this experimental model of heart failure.
Thirty-five patients with suspected acute myocardial infarction were studied in a randomised controlled trial to determine whether the catecholamine response to myocardial infarction was altered by administration of the beta blocker, sotalol, given within six hours of the onset of chest pain. Myocardial infarction evolved in 30 patients (15 placebo-treated, 15 sotalol-treated) and was associated with markedly increased plasma and urine noradrenaline and adrenaline levels. Intravenously administered sotalol was well tolerated and produced significant acute falls in blood pressure and heart rate. The reduction in heart rate was maintained in the sotalol group with once-daily therapy. Plasma levels of both catecholamines showed slow but very similar falls in the two groups, the decline being evident earlier for adrenaline than for noradrenaline. This was also reflected in the pattern of catecholamine excretion: significant falls in adrenaline but not noradrenaline excretion were seen on day 2 in both groups. Although mean plasma and urinary catecholamine levels tended to be higher in the sotalol group throughout the study, the differences between the sotalol and placebo groups for the changes in plasma or urinary catecholamines with time were not statistically significant. Episodes of ventricular tachycardia occurred in 68% of the patients on day 1 and 27% of patients on day 2. More patients in the sotalol group experienced episodes of ventricular tachycardia (sotalol 89% placebo 54%) but this difference was not statistically significant.(ABSTRACT TRUNCATED AT 250 WORDS)
Between 1971 and 1975, methicillin-resistant Staphylococcus aureus (MRSA) caused sporadic infection in eight Dublin hospitals although a case of bacteraemia was not recorded until 1976. From then on gentamicin-resistant MRSA rapidly became endemic in Dublin hospitals. The frequency of MRSA bacteraemia reached a peak in 1979-82 but MRSA infection remains an important problem. The most effective antimicrobial agent in treatment of invasive infection was vancomycin; little drug toxicity was seen. Where appropriate, concomitant surgical treatment such as debridement and drainage was usually necessary. Infection control measures directed at eliminating carriage proved effective in reducing spread. Molecular analysis showed two distinct MRSA phenotypes with similar phage-typing patterns. Gentamicin resistance was chromosomally encoded.
Chronic administration of intravenous adriamycin (1 mg . kg-1 twice weekly for 8 weeks) to rabbits resulted in a cardiomyopathy which was similar to that occurring in patients with adriamycin cardiotoxicity. We studied systemic and renal haemodynamics and the activation of vasoconstrictor mechanisms reflected by changes in plasma renin activity (PRA), noradrenaline (NA) and vasopressin (AVP) levels during the development of heart failure in this animal model. By 8 weeks cardiac failure was clearly established. At postmortem all animals had dilated hearts, pleural and pericardial effusions, ascites and hepatic congestion. Heart weights were increased (8.1 +/- 0.7 g in treated animals n = 9 vs 6.0 +/- 0.2 g in controls n = 9 p less than 0.05). Cardiac output (measured by thermodilution) fell at 8 weeks from 799 +/- 61 ml . min-1 to 624 +/- 44 ml . min-1 (n = 6 p less than 0.05) with a parallel fall in mean blood pressure from 85 +/- 2 mmHg to 75 +/- 4 mmHg. Total peripheral resistance rose in four of the six rabbits. Renal blood flow fell from 108 +/- 4 ml . min-1 to 61 +/- 6 ml . min-1 (p less than 0.05) by 8 weeks. Renal vascular resistance increased in all animals. PRA increased from 5.1 +/- 0.5 ng AI . ml-1 . h-1 to 11.6 +/- 2.6 ng AI . ml-1 . h-1 by 4 weeks (p less than 0.05) and remained elevated thereafter.(ABSTRACT TRUNCATED AT 250 WORDS)
6-Hydroxydopamine (2 microliter of 8 micrograms/microliter) was injected bilaterally into the lateral hypothalamus of male Sprague-Dawley rats to produce depletion of forebrain terminal fields and an accumulation of amines proximal to the site of injection. Two additional groups of animals were injected with either vehicle or were food and water intake-matched to those receiving 6-hydroxydopamine. Motor performance, food and water intake and body weight were measured in all animals for 2 days before and 6 days after injection. Animals were then sacrificed and brain tissue was prepared for biochemical assay or fluorescence histochemistry. The area of hypothalamic tissue proximal to 6-hydroxydopamine injection, that which contains the amine accumulation, was sectioned from the surrounding tissue with a biopsy punch and assayed for noradrenaline and dopamine content. The nucleus caudatus-putamen, basomedial hypothalamus, and tissue containing the olfactory tubercle and accumbens nucleus were also assayed. Fluorescent histochemical examination of tissue showed that in addition to the depletion of catecholamines in various terminal fields there was also an increase in the fluorescent amine accumulation proximal to the injection site in the impaired animals. This accumulation was not detected with the biochemical assay and is probably due to the occurrence of a masking effect by adjacent depletions. A significant rise in noradrenaline levels was seen in the basomedial hypothalamus of intake-matched controls. However, this too was not detected in 6-OHDA-treated animals and was probably due to masking by adjacent depletions in these areas.(ABSTRACT TRUNCATED AT 250 WORDS)
A new adrenomedullary scintigraphic imaging agent, iodine-131-labelled metaiodobenzylguanidine (MIBG), was used to localize a recurrent phaeochromocytoma in a 27-year-old man in whom the site of tumour could not be determined by any other means. MIBG scintigraphy is easy to perform and is highly specific for functioning aberrant adrenomedullary tissue. It complements other methods for localization of phaeochromocytoma and, under some circumstances, it may become the initial imaging procedure of choice in the screening of patients in whom the biochemical or clinical evidence suggests the presence of such tumours.
In hypertensive patients the time courses for the rise in serum MK-422 level, and fall in both angiotensin converting enzyme (ACE) activity and blood pressure after 10 mg of enalapril were very similar. A close relationship between serum MK-422 levels and percentage ACE inhibition could be demonstrated and the acute fall in blood pressure showed a good correlation with either measurement. With chronic administration, serum MK-422 levels increased linearly with the dose of enalapril. As in the acute study, close relationships between the serum MK-422 level and ACE inhibition, and between either measurement and the fall in blood pressure, could be demonstrated after chronic enalapril administration. However, when compared to the acute response, the ACE inhibition dose-response line was shifted to the right after chronic enalapril therapy suggesting that enalapril may lead to ACE induction in humans. This did not appear to influence significantly the blood pressure lowering effect of enalapril or the relationship between ACE inhibition and the hypotensive effect.