Energy expenditure in US automotive technicians and occupation-specific cardiac rehabilitation.

BACKGROUND: The standard exercise protocol for patients in a traditional cardiac rehabilitation (rehab) programme may not be adequate for preparing manual workers for a safe return to work, as these activities bear little resemblance to the physical movements and force exertion required in most industrial jobs. AIMS: To measure the energy expenditure as metabolic equivalents (METs) required for automotive technicians, to compare this MET level with that normally attained in traditional cardiac rehab programmes and to suggest cardiac rehab exercises for automotive technicians based on specificity of training. METHODS: Automotive technicians who volunteered to participate had their MET levels measured while they performed a defined series of work tasks in the service department of an automobile dealership. Their daily walking distance was also determined. RESULTS: Thirty-six of 95 eligible subjects participated; a response rate of 38%. Mean peak MET level was 7.1, less than the 8 METs target training goal often used in traditional cardiac rehab programmes. However, patients' outcome MET levels in cardiac rehab are usually measured by a treadmill stress test, whereas the subjects reached 7.1 METs while performing work tasks. The subjects walked an average of 5 km during a normal workday. CONCLUSIONS: Because MET level measurements are work specific, automotive technicians in a cardiac rehab programme should strive to reach and maintain a level of >7 METs while performing specific training exercises that mimic the work tasks they must do throughout the day. They can also benefit from traditional endurance training such as treadmill walking.

Endogenous cannabinoids mediate hypotension after experimental myocardial infarction.

OBJECTIVES: We sought to determine whether endocannabinoids influence hemodynamic variables in experimental models of acute myocardial infarction (MI). BACKGROUND: Hypotension and cardiogenic shock are common complications in acute MI. Cannabinoids are strong vasodilators, and endocannabinoids are involved in hypotension in hemorrhagic and septic shock. METHODS: The early effect of left coronary artery ligation on hemodynamic variables was measured in rats pretreated with the selective cannabinoid(1) receptor (CB(1)) antagonist SR141716A (herein referred to as SR, 6.45 micromol/kg body weight intravenously) or vehicle. Endocannabinoids produced in monocytes and platelets were quantified by liquid chromatography/mass spectrometry (LC/MS), and their effects on blood pressure and vascular reactivity were determined. RESULTS: After MI, mean arterial pressure (MAP) dropped from 126 +/- 2 mm Hg to 76 +/- 3 mm Hg in control rats, whereas the decline in blood pressure was smaller (from 121 +/- 3 mm Hg to 108 +/- 7 mm Hg, p < 0.01) in rats pretreated with SR. SR increased the tachycardia that follows MI (change [Delta] in heart rate [HR] = 107 +/- 21 beats/min vs. 49 +/- 9 beats/min in control rats, p < 0.05). The MI sizes were the same in control rats and SR-treated rats. Circulating monocytes and platelets isolated 30 min after MI only decreased MAP when injected into untreated rats (DeltaMAP = -20 +/- 5 mm Hg), but not in SR-pretreated rats. The endocannabinoids anandamide and 2-arachidonyl glycerol were detected in monocytes and platelets isolated after MI, but not in cells from sham rats. Survival rates at 2 h after MI were 70% for control rats and 36% for SR-treated rats (p < 0.05). Endothelium-dependent arterial relaxation was attenuated in SR-treated rats (maximal relaxation: 44 +/- 3% [p < 0.01] vs. 70 +/- 3% in control rats) and further depressed by SR treatment (24 +/- 5%, p < 0.01 vs. MI placebo). CONCLUSIONS: Cannabinoids generated in monocytes and platelets contribute to hypotension in acute MI. Cannabinoid(1) receptor blockade restores MAP but increases 2-h mortality, possibly by impairing endothelial function.

Ab initio structure determination of the lantibiotic mersacidin.

The crystal structure of mersacidin, a potential novel antibiotic against methicillin- and vancomycin-resistant Staphylococcus aureus strains, has been determined by ab initio methods. Despite all crystals being merohedrally twinned, an accurate structural model with an R value of 13.4% has been obtained at atomic resolution. With six molecules in the asymmetric unit and no atom heavier than sulfur, the structure corresponds to a protein of 120 amino acids and is the largest approximately equal-atom unknown structure solved by direct methods. In the crystal, the molecule assumes a compact fold different from that found by NMR in solution. Comparison of the NCS-related molecules reveals regions of variable flexibility. The region highly homologous to the related antibiotic actagardine is very rigid and possibly defines an essential building block of this class of new antibacterial substances.

[Cytokine expression of transforming growth factor-beta2 and interleukin-10 in squamous cell carcinomas of the head and neck. Comparison of tissue expression and serum levels]. / Expression der immun- supprimierenden Zytokine TGF-beta2 und Il-10 in Kopf-Hals-Tumoren. Vergleich von Serumwerten und Gewebeexpression.

Transforming growth factor-beta (TGF-beta) and interleukin 10 (Il-10) are cytokines that have a strong immunosuppressive ability. Their secretion by tumor cells is able to suppress an immunological response against tumor. Both factors have been shown to enhance tumor growth in glioblastomas and carcinoma of the breast. We determined the expression pattern of TGF-beta and Il-10 in squamous cell carcinomas of the head and neck (HNSCC) and a possible association with tumor stage and their pre-treatment cytokine serum levels. Cytokine expression in primary tumors and metastases of 21 patients with HNSCC was investigated by immunohistochemistry. To assess the TGF-beta2 and Il-10 levels in tumor patients before therapy 49 serum specimens were analyzed by ELISA. TGF-beta2 was detected in 95% of all tumor tissues analyzed and Il-10 in 79% of all tumors. TGF-beta2 was localized in tumor cells and tumor borders, while Il-10 was preferentially found in peritumoral connective tissue. Metastasizing tumors showed elevated pretreatment serum levels for TGF-beta2 and Il-10. There was no correlation between TGF-beta2 and Il-10 expression in tumor tissue and pretreatment serum levels. Our data show that the majority of HNSCC analyzed express TGF-beta2 and Il-10. A correlation between pretherapy elevated cytokine serum levels and tumor grade was shown.

Low dose flunarizine protects the fetal brain from ischemic injury in sheep.

Flunarizine, a calcium channel blocker, reduced cerebral damage caused by hypoxic-ischemic insults in neonatal rats and in fetal sheep near term. However, the high dose regimen used in these studies produced cardiovascular side effects that might have counteracted the neuroprotective properties of flunarizine. Therefore, the neuroprotective effect was tested in a low dose protocol (1 mg/kg estimated body weight). Twelve fetal sheep near term were instrumented chronically. Six fetuses were pretreated with 1 mg of flunarizine per kg of estimated body weight 1 h before ischemia, whereas the remainder (n=6) received solvent. Cerebral ischemia was induced by occluding both carotid arteries for 30 min. To exclude the possibility that the neuroprotective effects of flunarizine were caused by cerebrovascular alterations we measured cerebral blood flow by injecting radiolabeled microspheres before (-1 h), during (3 min and 27 min) and after (40 min, 3 h, and 72 h) cerebral ischemia. At the end of the experiment (72 h) the ewe was given a lethal dose of sodium pentobarbitone and saturated potassium chloride i.v., and the fetal brain was perfused with formalin. Neuronal cell damage was assessed in various brain structures by light microscopy after cresyl violet/fuchsin staining using a scoring system: 1, 0-5% damage; 2, 5-50% damage; 3, 50-95% damage; 4, 95-99% damage; and 5, 100% damage. In 10 other fetal sheep effects of low dose flunarizine on circulatory centralization caused by acute asphyxia could be excluded. In the treated group neuronal cell damage was reduced significantly in many cerebral areas to varying degrees (range for control group, 1.03-2.14 versus range for treated group, 1.00-1.13; p < 0.05 to p < 0.001, respectively). There were only minor differences in blood flow to the various brain structures between groups. We conclude that pretreatment with low dose flunarizine protects the brain of fetal sheep near term from ischemic injury. This neuroprotective effect is not mediated by changes in cerebral blood flow. We further conclude that low dose flunarizine may be clinically useful as a treatment providing fetal neuroprotection, particularly because the fetal cardiovascular side effects are minimal.

Weekly oral azithromycin as prophylaxis for agents causing acute respiratory disease.

Since the 1950s the U.S. military has used intramuscular injections of benzathine penicillin G (BPG) to control outbreaks of respiratory disease. In an effort to find an alternative prophylaxis, a randomized field trial was conducted among 1,016 male U.S. Marine trainee volunteers at high risk for respiratory disease. Participants were evaluated for evidence of acute respiratory infection by serological tests on pretraining and posttraining sera (63 days apart). Oral azithromycin prophylaxis (500 mg/w) outperformed BPG, preventing infection from Streptococcus pyogenes (Efficacy [E] = 84%; 95% confidence interval [CI], 63%-93%), Streptococcus pneumoniae (E = 80%; 95% CI, 50%-92%), Mycoplasma pneumoniae (E = 64%; 95% CI, 25%-83%), and Chlamydia pneumoniae (E = 58%; 95% CI, 15%-79%) in comparison with results in a no-treatment group. Azithromycin group subjects reported few side effects and less respiratory symptoms than the BPG and no-treatment groups. According to serological tests, oral azithromycin is an effective alternative prophylaxis to BPG for military populations.

Goldenhar syndrome among infants born in military hospitals to Gulf War veterans.

Reports in the popular press described the occurrence of Goldenhar syndrome among children of Persian Gulf War veterans (GWVs). The objective of this investigation was to compare the birth prevalence of Goldenhar syndrome among infants born in military hospitals to GWVs and to military personnel who were not deployed to the Gulf War (NDVs). Computerized hospital discharge data were reviewed for infants conceived after the war and born prior to the 1st of October, 1993, in medical treatment facilities (MTFs) operated by the U.S. Department of Defense. Medical records were evaluated for infants diagnosed at birth with at least one abnormality that might be related to Goldenhar syndrome. Two pediatricians, blinded to the parental Gulf War status of each infant, reviewed records. An estimated 75,414 infants were conceived after the Gulf War and born in MTFs during the study period (34,069 GWV infants and 41,345 NDV infants). Seven infants fulfilled the case criteria (five GWV infants and two NDV infants). All infants had fathers who served in the military at the time of their conception and birth. The birth prevalence was 14.7 per 100,000 live births among GWV infants (95% confidence interval [CI]: 5.4-36.4) and 4.8 per 100,000 live births (95% CI: 0.8-19.5) among NDV infants (relative risk: 3.03; 95% CI: 0.63-20.57; P values: [2-tailed] = 0.26, [1-tailed] = 0.16). The few affected cases and the broad confidence intervals surrounding the relative risk require that these results be interpreted with caution and do not exclude chance as an explanation for these findings.

Relation between cerebral oxygen delivery and neuronal cell damage in fetal sheep near term.

Asphyxia is one of the major causes for fetal brain damage. Although the quality of life of the so affected children is mostly very limited, the pathogenesis of hypoxic fetal brain damage is poorly understood. Particularly, there is a lack of studies, in which cerebral oxygen delivery is directly correlated to the extent of neuronal cell damage in the same brain specimens. Therefore, we measured cerebral oxygen delivery before (- 1 h), during (+3 min & +27 min) and after (+10 min, +4 h, +72 h) 30 min of ischaemia in 5 chronically catheterized normoxemic fetal sheep at 129 +/- 1 days gestation (term is at 147 days) using the microsphere method. In contrast to previous studies (Williams et al. 1990), we arrested carotid arterial blood flow above the lingual artery for 30 min during surgery. Seventy-two hours later the fetal brains were fixed in vivo under barbiturate anaesthesia of both the fetus and the ewe. After cerebral blood flow analysis neuronal cell damage was assessed with light microscopy in 43 specimens of the fetal brain after cresyl violet/fuchsin staining using a scoring system. After arrest of carotid arterial blood flow cerebral blood flow was reduced by 80%. Neuronal cell damage was focussed on the cerebral cortex. Almost no damage could be detected in deeper parts of the brain. In the cerebrum there was threshold oxygen delivery of 3 ml O2/100 g tissue/min, below which neuronal damage occurred. However, there was no correlation between cerebral oxygen delivery and neuronal cell damage in specimens of the cerebrum, in which oxygen delivery was less than 3 ml O2/100 g tissue/min, suggesting selective vulnerability. Therefore, in addition to the reduction in cerebral oxygen delivery, other variables, e.g. neurotransmitter release, receptor pattern or oxygen radicals, may be involved in the development of brain damage.