Magnetic field induced orbital polarization in cubic YbInNi4: determining the quartet ground state using x-ray linear dichroism.

We have been able to induce a linear dichroic signal in the Yb M(5) x-ray absorption white line of cubic YbInNi(4) by the application of a magnetic field. The nonzero integrated intensity of the magnetic field induced dichroic spectrum indicates a net noncubic 4f orbital polarization. A quantitative analysis of the temperature and field strength dependence establishes that the crystal-field ground state is a Γ(8) quartet. The results demonstrate the potential of magnetic field induced linear dichroism as a new powerful approach for the investigation of the degeneracy and orbital degrees of freedom of cubic heavy-fermion and Kondo systems.

[Definition and management of wound infections]. / Definition und Management der Wundinfektion.

Surgical site infections (SSI) in the postoperative period represent the sword of Damocles in surgery. In spite of the medical progress in recent years these infections cannot always be avoided and occur in 25% of all nosocomial infections in Germany. They also generate up to 50% of the required costs in this context. The consequences vary from extended duration of hospitalization to elevated mortality. The degree of contamination of surgical wounds is of great importance as well as the patient's immune status and comorbidities. Prevention of infected surgical wounds is essential and important measures should begin even prior to the surgical procedure. In addition, during and following the surgical procedure several standards have to be followed. Rapid confirmation of diagnosis and correct management of surgical site infections are essential for the course of the disease. This study provides information on development, prevention and therapy of surgically infected wounds.

The phenotypic patterns of essential hypertension are the key to identifying "high blood pressure" genes.

The genes that cause or increase susceptibility to essential hypertension (EH) and related animal models remain unknown. Their identification is unlikely to be realized with current genetic approaches, because of ambiguities in the genotype-phenotype relationships in these polygenic disorders. In turn, the phenotype is not just an aggregate of traits, but needs to be related to specific components of the circulatory control system at different stages of EH. Hence, clues about important genes must come through the phenotype, reversing the order of current approaches. A recent systems analysis has highlighted major differences in circulatory control in the two main syndromes of EH: (1) stress-and-salt-related EH (SSR-EH)--a constrictor hypertension with low blood volume; (2) hypertensive obesity--SSR-EH plus obesity. Each is initiated through sensitization of central synapses linking the cerebral cortex to the hypothalamic defense area. Several mechanisms are probably involved, including cerebellar effects on baroreflexes. The result is a sustained increase in sympathetic neural activity at stimulus levels that have no effect in normal subjects. Subsequent progression of EH is largely through interactions with non-neural mechanisms, including changes in concentration of vascular autacoids (e.g., nitric oxide) and the amplifying effect of structural changes in large resistance vessels. The rising vasoconstriction increases heterogeneity of blood flow, causing rarefaction (decreased microvascular density) and deterioration of vital organs. SSR-EH also increases food intake in response to stress, but only 40% of these individuals develop hypertensive obesity. Their brain ignores the adiposity signals that normally reduce eating. Hyperinsulinemia masks the sympathetic vasoconstriction through its dilator action, raises blood volume, whilst renal nephropathy and other diabetic complications are common. In each syndrome the neural and non-neural determinants of hypertension provide targets for identifying high BP genes. Reading the genome from the phenotype will require new approaches, such as those used in developmental genetics. In addition, transgenic technology may help verify hypotheses and examine whether an observed effect is through single or multiple mechanisms. To obtain answers will require substantial collaborative efforts between physiologists and geneticists.

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.

3-Alkyl- and 3-aryl-7H-furo[3,2-g]chromen-7-ones as blockers of the voltage-gated potassium channel Kv1.3.

3-Alkyl- and 3-aryl-7H-furo[3,2-g]chromen-7-ones were synthesised and studied for their effects on voltage-gated K+ and Na+ channels of the neuroblastoma cell-line N1E-115 and K+ channels of L-929 mouse-fibroblasts, stably transfected with mKv1.3. All furocoumarins tested showed Kv channel blocking activities, the most potent one in a half-blocking concentration of 0.7 microM.

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.

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.

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.

Assessment of prevalence of left ventricular hypertrophy in hypertension.

The reported prevalence of left ventricular hypertrophy (LVH) in human hypertension is much lower than that among animals with experimental hypertension. With current methods of determining left ventricular mass by M-mode echocardiography, the standard error of a single estimate is high and consequently so is the SD of the population distribution. This accounts for the large overlap in individual values of left ventricular mass index (LVMI) between hypertensive and normotensive groups. The high SD is due to the use of the cube algorithm for relating measurements made in a single plane to the whole left ventricle, and to the difference between actual and assumed left ventricular geometries. These are not problems with nuclear magnetic resonance imaging, which provides information about the entire left ventricle without assumptions about geometry. M-mode echocardiography is well suited for estimating differences between mean LVMI values for groups of subjects but it underestimates the prevalence of LVH. In most series only about 30% of hypertensives have been reported to have LVH. The estimated prevalence of structural remodelling is increased to 50-60% of the same group of subjects when 'low-SD' measurements such as wall thickness and the wall thickness: internal radius ratio are employed. The estimated prevalence of LVH and remodelling is still greater with multivariate discriminant function analysis, with which it is found in about 70% of hypertensives. Overall, the data suggest that prevalence of LVH in established hypertension is high. The 30% of subjects reported to have LVH on the basis of LVMI measurements that are beyond the limits of the control group probably have the most severe changes. The inability to detect lesser grades of left ventricular remodelling reliably is due to the way LVMI is derived by echocardiography, rather than to intrinsic inaccuracies. It suggests that existing approaches should be supplemented by greater use of 'low-SD' variables and discriminant functions. Detecting the full spectrum of left ventricular structural changes in individuals with hypertension is needed for risk assessment and, increasingly, for management aimed at minimizing irreversible myocardial damage. Nuclear magnetic resonance imaging provides 'global' and more accurate information about left chamber structure than does M-mode echocardiography but its cost at present is much greater. Nevertheless, the information provided by echocardiography may be adequate for the above applications, but the high SD of LVMI is a weakness. Greater use of 'low-SD' variables and multivariate discriminant functions may help overcome this problem.

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.

Assessment of medication compliance in alcoholics through UV light detection of a riboflavin tracer.

Compliance with the medication regimen in treatment trials for alcoholism appears to be a key determinant of treatment outcome. However, there is no consensus as to the best method to assess medication compliance. This study examines the feasibility of using ultraviolet light detection of a urinary riboflavin tracer to determine compliance with medication therapy. Six sets of urine specimens (with n ranging from 15 to 38) were rated independently by two judges. Test-retest reliability was high: 90 and 95% agreement for two judges. Inter-rater reliability ranged from 73 to 95% agreement between judges (mean = 88%), with correspondence kappa values ranging from 0.46 to 0.85 (mean = 0.69). Diaries, capsule counts, and spectrofluorimetric data were used to validate judges' ratings in four trials, including one in which subjects were alcohol-dependent participants in one of three pharmacotherapy trials. Rating accuracy was influenced by dosage, time interval between ingestion and urine collection, and previous dosing. Overall, ratings tended to be accurate, with incorrect judgments limited to specimens with low concentrations of urinary riboflavin. The results indicate that ultraviolet light detection of urinary riboflavin is a useful method for the assessment of patient compliance with medication regimens, including compliance of patients assigned to receive placebo in clinical trials of medications for alcoholism treatment.

Circulatory control and the supercontrollers.

NEUROHUMORAL SYSTEMS AS SUPERCONTROLLERS: The brain and closely linked hormone systems play a crucial part in short- and long-term cardiovascular control and have many features of adaptive control systems. The cardiovascular control system is a multivariate system, while changes in environmental conditions often result in alterations in system parameters and other non-linearities, in contrast to the fixed parameters of linear control systems. In blood pressure control these features are exemplified by diurnal circadian fluctuations, alterations in lifestyle and psychosocial stress. Because the neurohumoral controllers are involved in virtually all aspects of homeostasis, they can be regarded as supercontrollers. THE CIRCULATORY SYSTEM AND THE BRAIN: Analysis in conscious animals of the effects of circulatory disturbances suggests that the central nervous system integrates information from multiple sources of afferents. Integration of the information associated with most reflex and behavioural disturbances is mediated by many neuron groups at different levels of the neuraxis, including suprapontine brain regions. The disturbances considered include baroreflexes in intact animals, some central actions of alpha-methyldopa and reflex responses to hypoxia and haemorrhage. The operations involve the brain in comparisons of the relative magnitude of different inputs, while the occurrences of non-linear changes in baroreflex properties signify alterations in the parameters of the controller. NEUROHUMORAL MECHANISMS AND CARDIOVASCULAR DEVELOPMENT: Neurohumoral mechanisms also play a key role in cardiovascular development. Increased sympathetic activity early in life causes hypertension in spontaneously hypertensive rats (SHR) and accounts for the differences in blood pressure and structural variables from corresponding values in Wistar-Kyoto (WKY) rats. In contrast, the renin-angiotensin system affects early cardiovascular development in the same way in each strain, so that it is unlikely to be a cause of hypertension in SHR. However, after drug withdrawal following treatment of young rats with the angiotensin converting enzyme inhibitor enalapril, there were between-strain differences in late cardiovascular development. Late development is relatively small in SHR compared to WKY rats, which contributes to the long-term attenuation of hypertension in SHR and to the normalization of blood pressure in WKY rats.

Cardiovascular development after enalapril in spontaneously hypertensive and Wistar-Kyoto rats.

We studied the long-term effects after withdrawal of enalapril, an angiotensin-converting enzyme inhibitor, on tail systolic pressure and cardiovascular structural properties in spontaneously hypertensive rats (SHR) and Wistar-Kyoto rats (WKY). Observations in control rats were from 4 to 35 weeks of age, whereas treated rats received enalapril from 4 to 20 weeks and were studied for a further 15 weeks. We measured blood pressure and the ratio of left ventricle weight to body weight and derived methoxamine log dose-perfusion pressure curves in the isolated hindquarter bed. From the changes in resistance properties we also estimated the changes in structure using a model developed previously. During therapy, blood pressure was depressed to a common value in both strains. After drug withdrawal, by age 35 weeks, previously treated SHR developed only mild hypertension, whereas blood pressure of WKY had recovered to the corresponding control level. At 21 weeks, soon after enalapril was stopped, left ventricular development was depressed in both strains; the depression was slightly greater in SHR, but that of vascular resistance was proportionately similar in each strain. Late cardiovascular development between 21 and 35 weeks was attenuated in the previously treated groups. For the left ventricle, it was similar in each strain, but for the vasculature, late development was relatively smaller in SHR than WKY. In the former, the pattern of development between 21 and 35 weeks was the same as in untreated controls and appeared to be mediated in response to the rise in blood pressure.(ABSTRACT TRUNCATED AT 250 WORDS)

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.

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.

Cardiovascular hypertrophy and hypertension: causes and consequences.

In chronic hypertension, vascular resistance is raised and there is concentric left ventricular (LV) hypertrophy, at least in animal models. Together these changes enhance hemodynamic performance ("amplifier" properties) and help maintain elevated blood pressure (BP) and net microcirculatory exchange. Sometimes there is vascular "remodelling", with only luminal narrowing, but no net increase in medial mass. This can be related to non-uniform distribution of wall stress: when the amount of hypertrophy normalizes average wall stress, that on luminal side tends to be undercorrected accounting for preferential growth in that direction, whilst stress on the adventitial side is overcorrected, which results in a tendency to reabsorb material. In Goldblatt hypertension, about 20% of the rise in BP is due to the renal artery stenosis resistance, with the rest differing during the early and late phases: the early contribution is due to angiotensin II (AngII)-mediated systemic constriction and subtle fluid volume changes, whilst later on the cardiovascular amplifiers take over many of the actions of AngII. In SHR, trophic sympathetic nervous system actions are crucial for the rise in BP and development of structural changes and both contribute to the elevation of BP. Neonatal sympathectomy + prazosin treatment prevents hypertension and structural changes in SHR. Angiotensin converting enzyme (ACE) plays a similar role in cardiovascular development in SHR and Wistar Kyoto (WKY) rats. Prolonged administration of ACE inhibitors to SHR produces long term attenuation of hypertension because of an impaired capacity for cardiovascular development in adult animals. In human hypertension, long term treatment with common antihypertensive drugs is required to produce substantial regression of cardiovascular hypertrophy. Since it imposes marked non-uniformity on the distribution of capillary blood flow, with the potential for rarefaction and organ damage, therapy aimed at regression of hypertrophy is a worthwhile target.

Factors influencing the success of withdrawal of antihypertensive drug therapy.

We have reviewed the literature on the effect of withdrawal of antihypertensive therapy on return to hypertension. We also present our data from 83 patients in whom a 12-month follow-up period showed that 28% required re-institution of therapy within 10 weeks of withdrawal of medication, over half by 20 weeks, but a significant proportion (28%) stayed normotensive off therapy for a year. All patients had met the criteria for resumption of antihypertensive medication after 2 years of therapy. We also demonstrated predictive effects of left ventricular hypertrophy and duration of therapy on rate of redevelopment of hypertension. Our study raises the possibility that echocardiography may indicate the likelihood of a rapid return to hypertension when drug therapy is ceased.

Cardiac baroreflex in hypertension: role of the heart and angiotensin II.

Sigmoid logistic function curves provide a powerful means of characterizing the baroreceptor-heart rate reflex. In hypertension the operating range of the reflex is reset in the direction of the elevated resting BP; this can be accounted by rapid resetting of the threshold of the arterial baroreceptors. In addition, there is a deficit in the vagal component of the heart rate (HR) range. Reduction in gain occurs in moderate/severe hypertension, but may be absent in young primary hypertensives. All the changes are reversible, and reversibility of HR range and gain is related to reducing left ventricular hypertrophy or central blood volume rather than to reduction in BP. High plasma angiotensin II can further accentuate the vagal deficit. An input-output model has been developed from comparison of perivascular cuff and drug methods for eliciting the reflex, which place different loads on the heart; the greater load changes simulate many of the alterations in reflex properties observed in hypertension. We conclude that during changes in vasomotor tone in normal animals, about 70% of the drive for the cardiac baroreflex comes from arterial baroreceptors and about 30% from low threshold cardio-pulmonary baroreceptors. In hypertension, the vagal deficit in HR range is due to afferent interactions involving arterial and low and high threshold cardio-pulmonary baroreceptors.