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Biomedical subjects

P Korner

Publications and source records attributed to P Korner.

At least 19 recordsLinked to original sources
PubMed2004

In vivo dynamics of an immune response in the bumble bee Bombus terrestris.

Concepts from evolutionary ecology have recently been applied to questions of immune defences. However, an important but often neglected aspect is the temporal dynamics of the simple immune measures used in ecological studies. Here, we present observations for workers of the bumble bee Bombus terrestris on the dynamics of the phenoloxidase (PO) system, antibacterial activity, and the total number of haemocytes following a challenge with immune elicitors (LPS, Laminarin), over a time-span ranging from 1min to 14 days. The dynamics of the PO measurement showed a complex pattern and was correlated with haemocyte counts. Antibacterial activity, on the other hand, increased sharply between 2 and 24h post-challenge followed by a slow decrease. Surprisingly, the effects of a challenge lasted up to 14 days.

Adjuvants, Immunologic↗
PubMed2003

Effects of sperm on female longevity in the bumble-bee Bombus terrestris L.

The male ejaculate, particularly the accessory gland products, has been shown to affect female survival (as is best understood in Drosophila melanogaster). So far, these findings have primarily been discussed in the context of a sexual conflict and multiple mating. Here, we show that in the bumble-bee Bombus terrestris, male genotype influences female longevity even though B. terrestris generally is a singly mated species and male and female interests may thus be more convergent. In addition, the effect could not be owing to accessory gland products, as we artificially inseminated the queens with the content of the accessory testes only.

Analysis of Variance↗
PubMed2001

Allergy to bumblebee venom.

Allergy to bumblebee venom is a rare form of Hymenoptera venom allergy. Because bumblebees are increasingly used for the pollination of greenhouse plants, the prevalence of this Hymenoptera allergy has increased during the past decade. The clinical presentation, diagnosis and therapy of bumblebee venom allergy are similar to other Hymenoptera venom allergies. There is a significant immunological cross-reactivity between bumblebee and honeybee venom. It has been claimed that immunotherapy with honeybee venom can protect patients with bumblebee venom allergy. This concept, however, has been called into question after the finding of bumblebee venom-specific IgE lacking cross-reactivity to honeybee venom, and three cases of bumblebee venom-allergic patients in whom immunotherapy with honeybee venom was unsuccessful. Immunotherapy with pure bumblebee venom has been shown to be effective and safe, and is currently the treatment of choice in individuals who cannot avoid contact with bumblebees. Immunotherapy with honeybee venom, however, should be considered in patients with severe reactions to bumblebee stings and concurrent sensitization to honeybee venom.

Adult↗
PubMed1999

Liver function in postmenopausal women on estrogen-androgen hormone replacement therapy: a meta-analysis of eight clinical trials.

OBJECTIVE: To compare hepatic biochemical changes of a combined estrogen-androgen preparation with that of estrogen alone in postmenopausal women. DESIGN: Hepatic biochemical values from 511 surgical and 130 nonsurgically menopausal women being treated with hormone replacement therapy were pooled from eight similarly designed studies performed between March 1988 and January 1996 comparing esterified estrogen-methyl-testosterone preparations with esterified estrogen, conjugated equine estrogens, and placebo controls. The eight studies in this meta-analysis were controlled, randomized, multicenter, double-blind with identical or similar treatment arms. For hepatic biochemistry parameters, raw data summaries and mean changes from baseline values with standard error (SE) were evaluated for the dosages and treatment groups at various time periods throughout the studies. RESULTS: Eight controlled trials involving 641 surgically and nonsurgically menopausal women were included. Changes from the pretreatment baseline values of liver function were compared at 1, 3, 6, 12, 18, and 24 months of therapy. No patients demonstrated hepatotoxicity or clinically significant elevation of liver biochemistry values. None of the liver biochemistry changes measured in these studies were of clinical significance, nor were there biochemical differences between estrogen therapy alone compared with combined esterified estrogen-methyltestosterone preparation when administered to postmenopausal women during a period of up to 24 months. CONCLUSIONS: Combined esterified estrogen-methyltestosterone therapy (in doses of 0.625 mg esterified estrogen + 1.25 mg methyltestosterone or 1.25 mg esterified estrogen + 2.5 mg methyltestosterone) was found to be safe regarding hepatic function in postmenopausal women during the course of 24 months in eight controlled clinical trials.

Aged↗
PubMed1997

Shifting the circulatory control paradigm.

The current paradigm regards circulatory control as mediated by discrete cardiovascular receptor stimuli, through an array of relatively independent reflexes, with the arterial baroreflex the centrepiece of this schema. However, it is often difficult to fit the linear control model to the observed responses of the intact organism. Hence the need for a more realistic approach. A given disturbance acting on the body stimulates not only baroreceptors, but many other receptors, as well as providing the central nervous system (CNS) with behavioral cues, etc. The mix of stimuli is characteristic of the type and severity of the particular disturbance. The first task for the CNS, is recognition of the pattern of stimuli, which is often a non-linear process. This is mediated through a number of "integrative" centres in different parts of the brain, which compare the magnitude of stimuli from the various sources. The sum of excitatory and inhibitory influences in the efferents from these integrative centres project to "command" centres, e.g. in hypothalamus, amygdala or hindbrain. These generate the output patterns through activation of particular pools of autonomic motoneurons and by altering secretion of hormones. Both the recognition of afferent stimuli (including behaviour) and of the effector patterns, involve mechanisms above and below the pons.

Animals↗
PubMed1995

Placebo-controlled trial of fluoxetine as an adjunct to relapse prevention in alcoholics.

OBJECTIVE: The authors tested the hypothesis that fluoxetine, when used in combination with relapse prevention psychotherapy, directly reduces relapse frequency and severity for alcoholics. METHOD: The authors conducted a randomized, placebo-controlled trial of fluoxetine (up to a maximum of 60 mg/day) for 12 weeks in combination with weekly psychotherapy for 101 alcohol-dependent subjects who were not selected on the basis of comorbid major depression. Outcomes were measured at the end of treatment and 6 months after treatment. RESULTS: Placebo-treated subjects were more complaint with the medication regimen and remained in the study longer than fluoxetine-treated subjects. There was significantly less alcohol consumption in both groups during treatment than before treatment. These effects persisted during the posttreatment period. Although fluoxetine treatment had no significant effects on alcohol consumption, it reduced Hamilton Depression Rating Scale scores more than placebo treatment among subjects with current major depression. CONCLUSIONS: Fluoxetine at a dose of 60 mg/day is probably not of use for relapse prevention in alcoholics with mild to moderate alcohol dependence and no comorbid depression. In alcoholics with major depression, the drug may reduce depressive symptoms. Subsequent studies with fluoxetine should probably focus on more severely alcohol-dependent subjects or those with comorbid depression.

Adult↗
PubMed1995

Assessment of effects of two anti-hypertensive regimens on overall cardiovascular risk.

Anti-hypertensive drugs differ in their effects on other cardiovascular risk factors. To date there have been few attempts to quantitate the impact of such differences. Twenty five unmedicated patients with primary hypertension were randomised to initial therapy with either the calcium antagonist, felodipine, or a diuretic and doses titrated to achieve similar levels of blood pressure (BP). Second drugs were added if needed (metoprolol and prazosin, respectively). The aim was to determine over 1 year whether similar anti-hypertensive effects were associated with differences in a multivariate index of overall cardiovascular risk. The target supine diastolic blood pressure (DBP) (85 mm Hg) required the second agent in four of 13 evaluable patients in the felodipine group and six of 10 in the diuretic group. There was a significant rise in serum cholesterol and a fall in serum potassium in the diuretic group, but not in the felodipine group. Cardiovascular risk scores were ranked in percentiles in relation to the age-matched general population. This score fell to a greater degree in felodipine patients particularly over the first 6 months, but remaining lower at 12 months. Left ventricular hypertrophy assessed by echocardiography, another measure of cardiovascular risk, was generally unchanged by either regimen. At equivalent blood pressure levels, the calcium antagonist-based regimen had a greater benefit on cardiovascular risk, particularly in the first 6 months of therapy. This method may be widely applicable in the assessment of anti-hypertensive therapy.

Adolescent↗
PubMed1994

Buspirone treatment of anxious alcoholics. A placebo-controlled trial.

BACKGROUND: Symptoms of anxiety are common in alcoholics and may contribute to relapse following initiation of abstinence. Buspirone hydrochloride, a serotonin1A partial agonist, has a pharmacologic profile that may be particularly suited to the treatment of anxious alcoholics. METHODS: We conducted a randomized, 12-week, placebo-controlled trial of buspirone in 61 anxious alcoholics, all of whom also received weekly relapse prevention psychotherapy. Outcomes were measured at the end of treatment and at a 6-month follow-up evaluation. RESULTS: Buspirone therapy was associated with greater retention in the 12-week treatment trial, reduced anxiety, a slower return to heavy alcohol consumption, and fewer drinking days during the follow-up period. CONCLUSIONS: Buspirone appears to have a useful role in the treatment of anxious alcoholics. Further research is needed to clarify which patient characteristics and concomitant treatments result in optimal response to buspirone therapy.

Adult↗
PubMed1993

Sympathoadrenal system is critical for structural changes in genetic hypertension.

In spontaneously hypertensive rats (SHR) and Wistar-Kyoto (WKY) rats, we examined tissue and adrenal norepinephrine concentrations, left ventricular (LV) weight, LV weight/body weight ratio (LV/BW), hindquarter resistance properties, ie, perfusion pressures at maximum dilatation and constriction (PPmax, PPmin), and the slope of the methoxamine log dose-PP curve. In series 1, we studied 4-week-old controls (SHRc, WKYc), sympathectomized rats (SX; SHRsx, WKYsx), and SX rats also given prazosin (SXP; SHRsxp, WKYsxp). With SX and SXP, adrenal norepinephrine concentrations increased in both strains, but tissue (LV, muscle, kidney) norepinephrine was depleted. At 4 weeks, LV/BW, PPmin, and PPmax were all greater in SHRc than in WKYc. With SX, these differences between strains remained unchanged, but SXP abolished them completely, indicating the importance of blockade of alpha-adrenergic receptor stimuli of adrenal origin. In SHRc (but not in WKYc), there was evidence of reinnervation after 4 weeks of SX. Hence, in series 2, the SXP period was extended to 8 weeks, and we studied SHRc, WKYc, SHRsxp, and WKYsxp. Systolic blood pressure was already elevated at 4 weeks in SHRc, and by 35 weeks it was 64 mm Hg greater than in WKYc. At 21 and 35 weeks, LV/BW, PPmax, PPmin, and slopes were all greater in SHRc than in WKYc, and the findings suggested greater LV and vascular hypertrophy than at 4 weeks. In SHRsxp hypertension, LV hypertrophy and the vascular changes were completely prevented over the entire 35-week observation period. SXP mainly affected SHR and had few effects on WKY rats. The sympathetic nerves and adrenals are probably the sources of alpha-adrenergic receptor stimulation in young SHR. They account for the development of hypertension and for most of the cardiovascular structural differences between SHR and WKY rats.

Adrenal Glands↗
PubMed1991

Effects of exercise and other nonpharmacological measures on blood pressure and cardiac hypertrophy.

Reversal of left ventricular hypertrophy (LVH) is an important target of antihypertensive therapy. Nonpharmacological approaches such as weight reduction and exercise training have favorable effects on other risk factors. However, there are few data on their effects on LVH. Athletes have eccentric rather than concentric LVH. A 12-month exercise program in 13 unmedicated hypertensive subjects altered LV geometry, reducing LV wall thickness and increasing LV internal diameters (LVID). LV mass was unchanged, and the thickness/radius fell by 9%. Shorter-term studies have shown that the cardiac structural changes with a moderate exercise program occur rapidly and their onset lags only about 2 weeks behind blood pressure (BP) effects. Assessment of weight loss effects on LVH is complicated by the strong relationship between body weight and ventricular wall thickness. LVID, and LV mass. To some extent, this can be overcome by arbitrarily indexing to body surface area or height. The wall thickness/radius ratio is not related to body size. Weight reduction reduces BP and thickness/radius by 10% in controlled trials. Small studies have also reported reduction in LV mass after sodium restriction in hypertensive subjects. Studies with other nonpharmacological measures could make a substantial contribution to knowledge of their efficacy.

Blood Pressure↗
PubMed1991

What is the dose-response relationship between exercise training and blood pressure?

Most studies of exercise and blood pressure have used a standard exercise programme with a single level of physical activity. To determine the nature of the dose-response relationship however it is necessary to examine several levels of activity, preferably in the same subjects. We have recently performed several randomised crossover studies comparing different levels of regular exercise. The intensity and duration of exercise bouts were constant throughout the studies, but their frequency was varied. Standard bouts consisted of 30 min of bicycling at 60%-70% of maximum work capacity. The exercise was performed either three-weekly or 7-weekly in randomised order and each level was maintained for one month. In sedentary normal subjects three bouts of exercise/week for a total of 90 min lowered blood pressure by 10/7 mmHg. With seven bouts, i.e. a total of 210 min exercise/week, blood pressure was only slightly lower than 3-week exercise and was 12/7 mmHg below sedentary values. Responses to measures of physical fitness including maximum oxygen consumption and work capacity were linearly related to the amount of exercise performed each week. Similar results were obtained in hypertensives. Another randomised study was performed amongst expeditioners to Antarctica where environmental conditions determined that they were sedentary in winter and active in summer. The addition of either 3-week or 7-week exercise in winter significantly lowered blood pressure. In summer when the background level of activity was higher, blood pressure with no added exercise was similar to exercising levels in winter. There was no further fall in blood pressure with either 3-week or 7-week additional exercise.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1988

Relationships between the cardiovascular effects of alpha-methyldopa and its metabolism in pontomedullary noradrenergic neurons of the rabbit.

We compared the biotransformation of equipotent intracisternal (i.c., 600 micrograms/kg) and intravenous (i.v., 50 mg/kg) doses of alpha-methyldopa (alpha-MD) to alpha-methylnorepinephrine (alpha-MeNE) in the five major (A1, A2, A5, A6, and A7) noradrenergic nuclei of the rabbit brain, in relation to their cardiovascular effects. Peak effects on blood pressure and heart rate occurred 2-3 h after administration and persisted for 8 h. Three hours after i.v. alpha-MD, norepinephrine (NE) content throughout the five cell group regions was greatly reduced. However, total catecholamine (CA) content (NE plus alpha-MeNE) in the five cell groups increased by up to 300% due to accumulated alpha-MeNE. Eight hours after the i.v. dose, CA content throughout all five cell groups remained elevated. Following i.c. alpha-MD, a similar pattern of effect was observed in the A1, A2, and A5 regions. In the A6 and A7 regions, the effects were small and transient. Three hours after the i.c. dose, there was some biotransformation of alpha-MD but CA content was not affected. By 8 h, alpha-MeNE accounted for only a small fraction of the CA content. These results suggest that A1, A2, and A5 areas could be contributing to alpha-MD's cardiovascular effects. The elevation in CA content may be responsible for the activation of noradrenergic depressor pathways and blood pressure reduction.

Animals↗
PubMed1987

The place of exercise in the long-term treatment of hypertension.

The antihypertensive effects of exercise have been examined in 2 randomized studies of multiple levels of activity. In 12 normal subjects, 1 month's exercise 3 times weekly lowered blood pressure (BP) and vascular resistance. There was only a slightly greater effect after 7 times/week exercise. In most subjects there was a marked reduction in noradrenaline spillover rate, a measure of sympathetic activity. Exercise also improved glucose utilization and lowered plasma cholesterol. Thirteen previously untreated patients with essential hypertension had an average fall in BP of 11/9 and 16/11 mm Hg after 1 month each of 3/week and 7/week exercise respectively, again associated with fall in vascular resistance and a 20-30% reduction in plasma noradrenaline. BP remained lowered by 3/week exercise for 1 year. In patients who had BP controlled with drug for greater than 1 year, exercise 3 times weekly also prevented the redevelopment of hypertension after long-term drug therapy was ceased. Regular exercise is useful in the initial management of patients with mild hypertension. In more severely hypertensive patients, exercise may also be effective after an initial period of drug therapy.

Blood Pressure↗
PubMed1986

Differential effects of sino-aortic denervations on cardiac noradrenaline stores, turnover and neuronal re-uptake in normotensive and renal hypertensive rabbits.

The effects of sino-aortic denervation (SAD) on cardiac noradrenaline stores, turnover and neuronal re-uptake were examined in normotensive rabbits and rabbits with two-kidney, two wrapped hypertension. Ten to 12 days after SAD, left ventricular (LV) noradrenaline stores were reduced in renal hypertensives to 43% of that of the sham-operated rabbits, although there was no overt evidence of heart failure. This did not occur after SAD of normotensive rabbits. The reduction in noradrenaline content was accompanied by a reduction in [3H]-noradrenaline turnover time (4.4 h) compared with renal hypertensive (7.4 h) and the normotensive subgroups (9.3 h). Noradrenaline turnover rates were elevated by 25% in hypertensive compared with normotensive rabbits. Left ventricular tyrosine hydroxylase, dopamine-beta-hydroxylase and type A monoamine oxidase activities were similar in normotensive and hypertensive rabbits and were unaffected by SAD. Following SAD of hypertensive rabbits cardiac neuronal uptake for alpha-methylnoradrenaline was reduced by 33% compared with either the hypertensive or the normotensive rabbits. Sino-aortic denervation did not affect neuronal uptake in normotensives. These results suggest that following SAD of hypertensive rabbits, cardiac noradrenaline stores are depleted by enhanced cardiac sympathetic activity (reduction in [3H]-noradrenaline turnover time) and a reduction in neuronal re-uptake. It appears that the hypertensive hypertrophied heart is less able to tolerate chronic sympathetic overactivity and/or liability in coronary oxygen supply brought about by SAD.

Animals↗
PubMed1986

Echocardiographic measurement of left ventricular hypertrophy in untreated essential hypertension.

The prevalence of left ventricular hypertrophy (LVH) in human essential hypertension is uncertain. Echocardiography was used to calculate left ventricular wall thickness (WT), relative wall thickness (t/r) and left ventricular mass (LVM) in 52 normal subjects, 30 patients with borderline hypertension and 33 untreated patients with essential hypertension. In 52 normal subjects WT was independent of age, sex, BSA, BP or habitual physical activity, but LVM was significantly related to BSA and age. After correction of LVM for age and BSA, 88% of 33 patients with untreated essential hypertension had LVM greater than predicted which identified a larger proportion of hypertensives with LVH than previous studies suggest. Wall thickness measurement alone also indicated that about 80% of newly diagnosed hypertensives have LVH.

Adolescent↗
PubMed1986

The effects of changes in physical activity on major cardiovascular risk factors, hemodynamics, sympathetic function, and glucose utilization in man: a controlled study of four levels of activity.

The effects of four levels of activity on heart rate, blood pressure, cardiac index, total peripheral resistance index (TPRI), norepinephrine (NE) spillover rate, insulin sensitivity, and levels of lipids and some hormones were studied in 12 normal subjects. The randomized periods were (1) 4 weeks of below-sedentary activity, (2) 4 weeks of sedentary activity, (3) 4 weeks of 40 min of bicycling three times per week, and (4) 4 weeks of similar bicycling seven times per week. Exercise three times per week reduced resting blood pressure by 10/7 mm Hg (p less than .01) and it was reduced by 12/7 mm Hg after exercise seven times per week (both p less than .01). This was associated with reduction in TPRI, an increase in cardiac index, and cardiac slowing. At the highest level of activity, NE spillover rate, an index of sympathetic activity, fell to 35% of the sedentary value (p less than .001) in eight of 10 subjects. In two other subjects NE spillover rate rose, although blood pressure and TPRI were reduced. Metabolic changes included lowering of total cholesterol, but high-density lipoprotein level was unchanged. Insulin sensitivity rose by 27% after exercise three times per week, but declined to sedentary levels with seven times per week exercise. Maximum oxygen uptake increased linearly with activity. Exercise performed three times per week lowers blood pressure and should reduce cardiovascular risk. The same exercise seven times per week enhances physical performance with little further reduction in cardiovascular risk factors. Exercise is potentially a major nonpharmacologic method of lowering blood pressure.

Adult↗
PubMed1986

Evidence for a predominantly central hypotensive effect of alpha-methyldopa in humans.

We examined the time course and extent to which central and peripheral mechanisms contribute to the short-term effects of a 500-mg oral dose of alpha-methyldopa on supine mean arterial pressure, cardiac output, and total peripheral resistance, as well as its effects on total urinary excretion of norepinephrine and its metabolites, in five subjects with essential hypertension. Total peripheral resistance was reduced significantly 1 hour after alpha-methyldopa administration and remained so for the ensuing 7 hours of the study (p less than 0.05). A small but significant reduction in mean arterial pressure occurred 7 hours after the dose (p less than 0.05), while cardiac output did not change significantly. Total 24-hour urinary norepinephrine and metabolite excretion was reduced by 8.1 mumol (35% compared with placebo). The relative distribution of urinary norepinephrine metabolites was unaffected by alpha-methyldopa, and the catecholamine metabolites of alpha-methyldopa, alpha-methylnorepinephrine and alpha-methylnormetanephrine did not account for this reduction. Competitive inhibition of methyldopa transport across the blood-brain barrier and into the central nervous system by large oral doses of isoleucine antagonized most of the effect of alpha-methyldopa. The effects on total peripheral resistance were completely abolished, and small, insignificant changes during the 7-hour study were similar to those observed after placebo. Changes in mean arterial pressure were not significant; however, 24-hour total urinary norepinephrine and metabolite excretion increased by 6.1 mumol to 22.7 mumol (24.7 mumol excreted after placebo). Adding benserazide to the alpha/methyldopa-isoleucine dose regimen in an attempt to inhibit any residual, presumably peripheral, effects of alpha-methyldopa caused little, if any, further antagonism.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗