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Biomedical subjects

D Kaye

Publications and source records attributed to D Kaye.

At least 19 recordsLinked to original sources
PubMed2003

Sympathetic nerve activity and neurotransmitter release in humans: translation from pathophysiology into clinical practice.

AIM: There has been a revolution in cardiovascular neuroscience in recent years with, in some cases, translation into clinical practice of the knowledge of pathophysiology gained through application of sympathetic nerve recording and catecholamine isotope dilution methodology. OBESITY-RELATED HYPERTENSION: An earlier hypothesis, based on findings in most models, was that weight gain in obesity is due in part to sympathetic nervous underactivity reducing thermogenesis. Microneurography and regional noradrenaline spillover measurements in human obesity have disproven this hypothesis, weakening the case for the use of beta3-adrenergic agonists to stimulate thermogenesis. Sympathetic nerve firing rates in post-ganglionic fibres directed to the skeletal muscle vasculature are increased, as is renal sympathetic tone, with a doubling of the spillover rate of noradrenaline from the kidneys. Given these findings, antiadrenergic antihypertensive drugs may be the preferred agents for obesity-related hypertension, but this has not been adequately tested. ESSENTIAL HYPERTENSION: Whether stress causes high blood pressure, previously hotly debated, has been under recent review by an Australian Government body, the Specialist Medical Review Council. Despite medicolegal implications, the ruling was that stress is one proven cause of hypertension. The judgment was reached after consideration of the epidemiological evidence, but in particular the described neural pathophysiology of essential hypertension: (a) persistent sympathetic nervous stimulation is commonly present, (b) suprabulbar projections of noradrenergic brainstem neurones are activated and (c) adrenaline is released as a cotransmitter in sympathetic nerves. These were taken to be biological markers of stress. CARDIAC FAILURE: At one time, the failing heart was thought to be sympathetically denervated. Longterm administration of inotropic adrenergic agonists, to provide the cardiac catecholamine stimulation thought to be lacking, increased mortality. Noradrenaline isotope dilution methodology subsequently demonstrated that the sympathetic outflow to the heart was preferentially activated, cardiac noradrenaline spillover being increased as much as 50-fold. The level of stimulation of the cardiac sympathetic nerves was the most powerful predictor of death. These observations provide the theoretical foundation for the very successful introduction of beta-adrenergic blockers for treatment of heart failure.

Autonomic Nervous System Diseases↗
PubMed2003

Antenatal and intrapartum risk factors for birth asphyxia among emergency obstetric referrals in Mulago Hospital, Kampala, Uganda.

BACKGROUND: Many perinatal deaths follow birth asphyxia that occurs in newborn babies of women who are referred on developing life-threatening obstetric complications. OBJECTIVE: To determine the antenatal and intrapartum risk factors for severe birth asphyxia among babies delivered by women admitted as emergency obstetric referrals. DESIGN: Case-control study. SETTING: Mulago hospital, the National Referral Hospital, Kampala, Uganda. SUBJECTS: Cases were newborn term babies (and their mothers) with a 5-minute Apgar score 4 or less (birth asphyxia). Controls were term newborn babies with a 5-minute Apgar score more than 4. MAIN OUTCOME MEASURES: Antepartum and intrapartum risk factors among newborn babies (and their mothers) from socio-demographic characteristics, obstetric complications or labour management. The Odds ratios (OR) for various outcomes were calculated using the Statistical Assistance Software (SAS) version 6.2 (Windows), and are presented with their 95% confidence intervals (C1) and p-values. RESULTS: There was no association between socio-demographic factors and birth asphyxia. Antepartum hospitalization, antepartum or intrapartum anaemia, antepartum hemorrhage and severe pre-eclampsia/eclampsia were significantly associated with birth asphyxia; the respective ORs and 95% C1 were 1.73 (1.09-2.75), 5.65 (3.36-9.50), 2.12 (1.11-4.05) and 10.62 (2.92-38.47). Augmentation of labour with oxytocin, premature rupture of membranes, meconium staining of liquor amnii, vacuum extraction, caesarean section, low birth weight and mal-presentations were significantly associated with birth asphyxia with ORs of 5.76 (2.20-15.05), 2.23 (1.31 -3.37), 6.40 (2.76-14.82), 2.16 (1.28-3.67), 2.36 (1.07-5.20) and 6.32 (3.57-11.20) respectively. CONCLUSIONS: Early recognition of these complications among emergency obstetric referrals, followed by prompt and appropriate management, may reduce the perinatal deaths from birth asphyxia.

Apgar Score↗
PubMed2003

Maternal mortality and associated near-misses among emergency intrapartum obstetric referrals in Mulago Hospital, Kampala, Uganda.

BACKGROUND: Many maternal deaths (as well as related severe morbidity) are of women who do not attend antenatal care in a given health unit but are referred there when they develop life-threatening obstetric complications. OBJECTIVE: To determine the reproductive characteristics of emergency obstetric referrals, and determine the contribution of emergency obstetric referrals to severe acute maternal morbidity (near-misses) and maternal mortality. STUDY DESIGN: Descriptive cross-sectional study. SETTING: Mulago hospital, the National Referral hospital, Kampala, Uganda, from 1st March to August 30th 2000. SUBJECTS: Nine hundred and eighty three consecutive women admitted as emergency obstetric referrals in labour or puerperium. INTERVENTIONS: Subjects were followed from time of admission to discharge (or death). They were interviewed (or examined) to obtain data on socio-demographic characteristics, reproductive history, obstetric outcome of the index pregnancy, obstetric complications and cause of death. Their records were reviewed to determine evidence of severe acute morbidity from acute organ/system dysfunction, using the definition by Mantel et al. These data were analysed using the Epilnfo computer programme in terms of means, frequencies and percentages. MAIN OUTCOME MEASURES: Socio-demographic characteristics, obstetric complications, cause of deaths, cause and type of near miss mortality and case fatality rates. RESULTS: Of the 983 referrals, over 100 were near-misses and 17 died. Using the definition of Mantel et al of near-misses enabled identification of six times as many near-misses as maternal deaths. The commonest causes of death were postpartum haemorrhage and eclampsia. Low status was highly associated with both maternal deaths and near misses. CONCLUSION: In developing countries, with poor obstetric services, emergency transfers in labour are very common. These women, who are of low status, contribute significantly to maternal mortality and morbidity.

Adult↗
PubMed2001

beta-blockers, angiotensin II, and ACE inhibitors in patients with heart failure.

Blood concentrations of angiotensin II are often raised in patients with heart failure, despite treatment with angiotensin-converting-enzyme (ACE) inhibitors. We compared concentrations of angiotensin II in two groups of matched patients, receiving ACE inhibitor therapy with or without concomitant administration of beta-blockers. Concentrations of angiotensin II were lower in individuals taking beta-blockers than in those who were not (geometric mean 1.1 [95% CI 0.4-2.7] vs 15.5 [4.6-52.6] fmol/mL, 95% CI for difference 3-59). Our findings indicate that a reduction in angiotensin II concentrations might contribute to the therapeutic benefits of beta-blockade in heart failure, especially in patients who simultaneously receive ACE inhibitor treatment.

Adrenergic beta-Antagonists↗
PubMed2001

The sympathetic neurobiology of essential hypertension: disparate influences of obesity, stress, and noradrenaline transporter dysfunction?

Although the importance of sympathetic nervous activation in the pathogenesis of essential hypertension is well documented, the exact pathophysiology of the sympathetic nervous dysfunction present remains to be delineated. This review details three relatively new findings of disturbed sympathetic neurobiology in hypertension. Adrenaline cotransmission is present in the cardiac sympathetic nerves of patients with essential hypertension, as it is in patients with panic disorder, providing presumptive evidence of exposure to high levels of mental stress in hypertensive patients. In lean patients with hypertension there is also evidence of faulty noradrenaline reuptake into the sympathetic nerves of the heart, an abnormality amplifying the sympathetic neural signal by impairing removal of noradrenaline from the synaptic cleft. If both abnormalities are present in the sympathetic nerves of the kidneys also (which we did not test), there would most probably be a direct contribution to hypertension development. In the kidneys the causal chain between sympathetic overactivity and the development of hypertension is stronger than for the heart. In obesity-related hypertension there is evidence that renal sympathetic tone is high, based on approximately a doubling of the measured rate of spillover of noradrenaline into the renal veins. This increase in sympathetic outflow to the kidneys appears to be a necessary but apparently not a sufficient cause for the development of clinical hypertension, commonly being present also in overweight people with blood pressure in the normotensive range. High renal sympathetic tone in the latter, of course, may well still contribute to elevation of their pressure level, although not on such a scale as to cause clinical hypertension.

Adrenergic Antagonists↗
PubMed2001

Sympathetic nervous system and insulin resistance: from obesity to diabetes.

As the world faces an obesity "epidemic," the mechanisms by which overweight is translated into insulin resistance, hypertension, and diabetes need to be better understood. Although the processes of transition remain uncertain, overactivity of the sympathetic nervous system appears pivotal. In obesity, there is stimulation of sympathetic outflow to the kidneys, evident in increased rates of spillover of noradrenaline into the renal veins, and to skeletal muscle vasculature, demonstrated with microneurography. The cause is unclear, but possibly involves the stimulatory action of leptin released from adipose tissue, or from within the brain, for which there is recent evidence in human obesity. The high renal sympathetic tone contributes to hypertension development by stimulating renin secretion and through promoting renal tubular reabsorption of sodium. Neurally mediated skeletal muscle vasoconstriction reduces glucose delivery and uptake in muscle. Impairment of glucose uptake by skeletal muscle is a hallmark of insulin resistance syndromes. Pharmacologic sympathetic nervous suppression within the central nervous system with imidazoline receptor-binding agents such as rilmenidine is a logical therapeutic approach for lowering blood pressure (BP) in patients with essential hypertension, in whom sympathetic activity is often increased. In addition, drugs of this class appear to have the capacity to favorably modify insulin sensitivity, which has particular relevance in the treatment of hypertensive diabetic patients. In the hypertension accompanying maturity onset obesity, with recent recommendations from advisory bodies setting lower goal BP, and with these lower targets often being reached only with combinations of antihypertensive agents, it is advisable that all drugs used in combination therapy have a favorable or at least a neutral effect on insulin resistance.

Antihypertensive Agents↗
PubMed2001

Improved outcomes from a comprehensive management system for heart failure.

AIMS: Congestive heart failure (CHF) is associated with a high readmission rate after diagnosis. We assessed the ability of a comprehensive management program (CMP) for CHF to reduce readmissions with secondary endpoints of improving quality of life, exercise capacity and targeted drug doses. METHODS AND RESULTS: Patients (pts) with: New York Heart Association Class (NYHA) III or IV CHF; left ventricular ejection fraction <40%; and stable outpatient therapy were assigned to a CMP of cardiology assessment intensive education and referral to a tailored exercise program. Forty-two pts (35 M, 7 F, mean age 54 years, S.D. 12 years) were enrolled. Two pts were transplanted, two died during follow-up and two were lost to follow-up. Hospital admissions were reduced by 87.2%, (mean 1.05, S.D. 0.98, admissions per pt to mean 0.08, S.D. 0.28, admissions per pt at 6-month follow-up; P<0.0001). ACE-inhibitor dose increased by 42% (P<0.0008) and beta-blocker dose increased by 61% (P<0.0001). NYHA Class, 6-min walk and quality of life scores all improved significantly (P<0.0001). CONCLUSION: A CMP improves QOL and exercise capacity as well as substantially reducing hospital admissions in CHF pts. This study validates the benefit of intensive outpatient care of CHF.

Aged↗