Relation of body mass index, physical fitness, and the cardiovascular risk profile in 3127 young normal weight men with an apparently optimal lifestyle.

Obesity is a well-accepted cardiovascular risk factor associated with hypertension and hyperlipidaemia. A body mass index (BMI) within the range of 18.5-25 kg/m(2) is considered normal. To prevent cardiovascular diseases regular physical activity and abstinence from smoking are strongly recommended. Since it is not evident that a lower optimal threshold exists concerning cardiovascular risk factors if other lifestyle conditions are apparently optimised, we studied the relation between BMI and vascular risk factors in 3127 hyperhealthy Caucasian males. They were aged between 18 and 23 y, were nonsmokers, without regular alcohol intake, and had at least 3 h of sports activity per week. Their BMI was below 25 kg/m(2). Low BMI revealed to be significantly associated with high physical fitness, low blood pressure, and low serum lipids. The lower the BMI was, the more favourable these parameters were. Thus, the threshold for an optimal BMI concerning cardiovascular risk factors might be far below 25 kg/m(2) even if other lifestyle conditions are apparently optimal.

Production of isometric forces during sustained acceleration.

BACKGROUND: The operation of high-performance aircraft requires pilots to apply finely graded forces on controls. Since they are often exposed to high levels of acceleration in flight, we investigated to what extent this ability is degraded in such an environment. METHODS: Twelve healthy non-pilot volunteers were seated in the gondola of a centrifuge and their performance was tested at normal gravity (1 G) and while exposed to sustained forces of 1.5 G and 3 G oriented from head to foot (+Gz). Using an isometric joystick, they attempted to produce force vectors with specific lengths and directions commanded in random order by a visual display. RESULTS: Acceleration had substantial effects on the magnitude of produced force. Compared with 1 G, maximum produced force was about 2 N higher at 1.5 G and about 10 N higher at 3 G. The size of this effect was constant across the different magnitudes, but varied with the direction of the prescribed force. CONCLUSIONS: Acceleration degrades control of force production. This finding may indicate that the motor system misinterprets the unusual gravitoinertial environment and/or that proprioceptive feedback is degraded due to increased muscle tone. The production of excessive isometric force could affect the safe operation of high-performance aircraft.

Reduced tolerance of simulated altitude (4200 m) in young men with borderline hypertension.

BACKGROUND: Primary hypertensives who are acutely exposed to hypoxic hypoxia show an enhanced reactivity of arterial chemoreceptors as well as an exaggerated response of the sympathetic nervous system. Since these phenomena could influence their ability to tolerate sustained hypoxic hypoxia, this study was performed to determine whether persons predisposed to hypertension have a normal tolerance of simulated high altitude. METHODS: Subjects were 18 young men with a family history of hypertension (sons of hypertensives, SOHT) whose BP values were in the upper normal or borderline hypertensive range. Controls were 15 young men without parental hypertension (sons of normotensives, SONT) who had normal BP values. Each subject underwent both a control and an altitude experiment. The latter consisted of an 8-h exposure to hypobaric hypoxia (equivalent to 4200 m) while resting supine in an altitude chamber. Fluids were administered by mouth and by intravenous line to produce sustained diuresis. Variables measured included heart rate, BP, respiratory rate, O2 saturation, urine flow rate, and sodium excretion. RESULTS: All subjects tolerated the control experiment and all SONT also completed altitude exposure. However, 8 of 18 SOHT developed antidiuresis and had to leave the chamber early due to symptoms of mild acute mountain sickness. Compared with SONT, SOHT exhibited more stable cardiorespiratory parameters at altitude. CONCLUSIONS: The data support the hypothesis that borderline hypertensives have stronger cardiorespiratory responses to altitude than controls, a response that is compatible with higher excitability of their arterial chemoreceptors. However, their altitude tolerance is reduced even at rest, probably because of the renal effects of an exaggerated response in the sympathetic nervous system.

Synthetic 2-aroylindole derivatives as a new class of potent tubulin-inhibitory, antimitotic agents.

A new class of simple synthetic antimitotic compounds based on 2-aroylindoles was discovered. (5-Methoxy-1H-2-indolyl)-phenylmethanone (1) as well as analogous 3-fluorophenyl- (36) and 3-methoxyphenyl (3) derivatives displayed high cytotoxicity of IC(50) = 20 to 75 nM against the human HeLa/KB cervical, SK-OV-3 ovarian, and U373 astrocytoma carcinoma cell lines. The inhibition of proliferation correlated with the arrest in the G2/M phase of the cell cycle. In in vitro assays with tubulin isolated from bovine brain, in general antiproliferative activity correlated with inhibition of tubulin polymerization. Thus, the antimitotic activity of 2-aroylindoles is explained by interference with the mitotic spindle apparatus and destabilization of microtubules. In contrast to colchicine, vincristine, nocodazole, or taxol, 1 did not significantly affect the GTPase activity of beta-tubulin. Interestingly, selected compounds inhibited angiogenesis in the chorioallantoic membrane (CAM) assay. In xenograft experiments, 1 was highly active after oral administration at 200 mg/kg against the human amelanocytic melanoma MEXF 989 in athymic nude mice. We conclude, that 2-aroylindoles constitute an interesting new class of antitubulin agents with the potential to be clinically developed for cancer treatment.

Theophylline improves acute mountain sickness.

A randomized two-part study was conducted in order to determine the efficacy of theophylline in the treatment of acute mountain sickness during fast ascent to altitudes >2,500 m. Fourteen healthy male subjects participated in a randomized single-blind placebo-controlled crossover study carried out in a decompression chamber (simulated altitude 4,500 m). A second randomized single-blind, placebo-controlled study was conducted at a high-altitude research laboratory (3,454 m) and included 21 healthy male subjects. The study medication was either 375 mg oral slow-release theophylline (250 mg if <70 kg) or a matched placebo tablet taken twice daily. The acute mountain sickness score (AMSS) was assessed three times a day, beginning 18 h prior to altitude exposure and continuing for 18 h after altitude exposure. In addition, measurements of respiratory frequency, pulse rate, oxygen saturation and arterial blood gas levels were performed. Acute mountain sickness was significantly reduced by theophylline during the decompression chamber study (mean+/-SD 1.2+/-0.9) with placebo versus 3.6+/-0.8 with theophylline; p=0.03). During the high-altitude study, subjects with theophylline showed a significantly lower AMSS on arrival and after 18 h at altitude (0.6 versus 2.3, p=0.03). Oxygenation was improved in both parts of the study. In conclusion, oral slow-release theophylline improves acute mountain sickness.

A study on the effect of oxygen bolus breathing or pressure breathing on oxygen saturation, at rest or under physical strain (bicycle ergometer) at 14,000 ft altitude.

At an altitude of about 3000 m even healthy people suffer from hypoxemia due to the low oxygen partial pressure. As a physiological countermeasure the oxygen partial pressure is increased. In the present study the following procedures are looked into: 1. Pressurized breathing, 2. Oxygen bulus breathing. It was found out that both procedures are appropriate to increase the oxygen partial pressure efficiently. However, bolus breathing is more effective, since an almost 100% hemoglobin saturation may be achieved even with small bolus volumes when the subject is at rest or under little physical strain. Pressurized breathing seems to be an appropriate emergency measure when a sudden pressure loss occurs in an aircraft for a short while provided that the subject is familiar with the breathing technique.

Distributed current analyses of bi-hemispheric magnetic N1m responses to ipsi/contralateral monaural stimuli from a single subject.

Magnetoencephalographic (MEG) responses of both auditory cortices to simple auditory stimuli presented monaurally to either ear were recorded from a single subject. A distributed current model and a current dipole model were used to analyse the responses at the latency of the dominant N1m complex. At the N1m the current density was localised to a single area and was consequently well modelled by a single current dipole close to the peak current density. In the left hemisphere, the contralateral response (as identified by the peak current density) preceded the ipsilateral response by 3 msec. This value was 7 msec for the right hemisphere. Evidence was found in the right hemisphere of a posterior-anterior movement along the sylvian fissure. Also, the left hemisphere N1m sources were all represented more posterior than the right hemisphere N1m sources.

Functional 3D localization of cerebrovascular accidents by magnetoencephalography (MEG).

Spontaneous magnetic slow wave brain activity can be used to locate the underlying sources with sufficient accuracy by using the single current dipole model. To locate focal sources from spontaneous activity a tool had to be developed to extract focal densities of dipoles across time-the dipole density plot. The first version works on discrete volume units and is used for screening. The second version avoids a possible localization error and works continuously and this even is done on individual slices. The DDP seems to be a valuable tool for extracting and separating different focal sources from the background activity. Not only brain infarctions and haemorrhages (and cysts and angiomas) could be located, but also functional sources associated with TIAs even one week after the symptoms. First results let us assume that clinically silent TIAs also (in analogy to clinically silent brain infarctions) could be detected and located.

Air humidity and carotid rete function in thermoregulation of the goat.

1. The effects of air humidity on respiratory rate have been studied in conscious goats exposed to an air temperature of + 33 degrees C. Before the experiments the animals had been chronically implanted with hypothalamic thermodes and intravascular heat exchangers to manipulate hypothalamic and general body core temperatures.2. Raising air humidity from 37 to 96% at constant air temperature resulted in a rise of respiratory rate, an immediate increase in hypothalamic temperature and a delayed smaller increase in general body core temperature.3. The rise of respiratory rate was smaller when general body core temperature was clamped at its control level and was absent when hypothalamic and general body core temperatures were clamped at their control levels during the humid air phase.4. It is concluded that the effect of high air humidity on respiratory rate in goats is predominantly the result of a rise in hypothalamic temperature acting on local thermosensitive structures. The carotid rete heat exchanger is thought to provide the thermal link between the evaporating surfaces of the upper respiratory tract and the hypothalamus.5. This function of the carotid rete heat exchanger is restricted to heat stressed animals. In animals subject to central cooling no local effects on hypothalamic temperature could be observed when the temperature of the inspired air was altered from + 33 to - 17 degrees C.

Xenogeneic skin and kidney transplants in a closely related canine system, fox-dog.

Fox kidney and skin grafts were transplanted into dog recipients. Fox kidneys, transplanted en bloc into untreated dogs, survived 6.2 +/- 0.4 days. The skin transplants survived 5.9 +/- 1.4 days. The grafted kidneys showed almost normal function before rejection. Both skin and kidney rejection were mediated through a cellular mechansim. Performed natural antibodies against donor tissue were not present in the serum of the recipients. These results combined with absorption studies suggested a close relationship between fox and dog, but different number and morphology of chromosomes, immunoelectrophoretic patterns of serum proteins, and disparities of the transplantation antigens proved that the fox is a species quite separate from the dog. It was concluded that the fox-dog system, with its similarity to the chimpanzeeman relationship, offers a unique model to study clinically applicable methods of managing xenografts between closely related species.