Stretch activation and myogenic oscillation of isolated contractile structures of heart muscle

Summary Glycerinated or freeze-dryed fibre bundles of heart muscles (papillary and trabecular muscles of rabbit or guinea pig) show in ATP-salt solution with about 10^–6M Ca²⁺ an active, delayed tension increment after quick or sinusoidal stretching. The active tension increase is completely different from the passive tension increment caused by stretching of the elastic structures of the muscle; this well known length dependence of tension is also in phase with the length changes (or the tension-phase preceeds the length-phase in visco-elastic bodies). On the other hand, the active tension increase is delayed with respect to the length change; this can be observed very well after rectangular changes in length. The delayed activation of the contractile bonds at stretch and the delayed deactivation at shortening induce the muscle-during sinusoidal length changes in a characteristic frequency range-to produce power output. The frequency range corresponds to the heart beat frequency of the living muscle. Temperature rise and inorganic phosphate accelerate, Mg-ions and ADP retard the contraction speed. Ca-ions influence only the amount of the isometric tension, but not the contractile velocity.Supported by the Deutsche Forschungsgemeinschaft (Grant RU 154/3).     

Aging does not affect the sleep endocrine response to total sleep deprivation in humans

Aging is associated with decreased sleep continuity, slow wave sleep (SWS), growth hormone (GH) release and an increased hypothalamo-pituitary-adrenocortical (HPA) system activity. Total sleep deprivation (TSD) is a strong stimulus for sleep. To determine if aging affects the response to TSD, for the first time the combined effects of TSD on conventional and spectral sleep electroencephalographic (EEG) parameters and GH, cortisol and prolactin secretion were compared in elderly (60–80 years; n = 7) vs. younger subjects (20–30 years; n = 7). MANOVA revealed a reduction of SWS in the elderly. TSD led to an increase in SWS, a decrease in sleep onset latency, rapid eye movement (REM) density and by trend REM-latency without a global group difference. GH was reduced, whereas prolactin was enhanced in the elderly. After TSD GH was unchanged and prolactin secretion was enhanced without group difference. Thus, the plasticity of the sleep-endocrine system in response to TSD is sustained during aging. The possible involvement of the GABAergic system, that seems not to be severely impaired with age, is proposed.     

Cavernous Haemangiomas of the Spinal Cord. A Review of 117 Cases

 The data of 48 studies (published between 1903 and 1996), presenting information of all together 107 patients (108 lesions) regarding pre-treatment clinical and radiological factors, treatment strategies, and the outcome, plus our own experience of nine patients were retrospectively re-analyzed. The prognostic influence of pre-treatment factors was estimated with the chi-square statistics. Clinical evaluation before/after treatment was performed using the Frankel scale. The average bleeding rate was obtained from the ratio of percentage of first bleeding events in the population to the mean age of the population.  There were 47 males and 69 females (aged from twelve to 88 years). Thirty nine percent of the lesions were found in the cervical, 54% in the thoracic (30% upper, 24% lower) and 7% in the lumbar cord. The peak age of presentation was in the fourth decade, the median duration of symptoms was 32 months. Clinical symptoms before treatment were progressive in all cases. Three patterns of clinical presentation could be identified: a) episodes of stepwise clinical deterioration (30%), b) slow progression of neurological decline (41%), c) acute onset with rapid or gradual decline over weeks or months (26%). 58% of the lesions showed clinical or radiological signs of haemorrhage. In 66% of surgical patients (91 efficiently documented cases), clinical improvement was achieved, 28% remained unchanged and 6% deteriorated. Whereas age, sex and lesion location had no influence on the results, duration of symptoms (<three years) correlated significantly to a better outcome (p<0.02).  Surgical management in symptomatic patients is recommended. Once clinical signs caused by the malformation have appeared, the patients tend to experience progressive neurological deterioration.     

The effect of remifentanil on biliary tract drainage into the duodenum

Opioids cause spasm of the sphincter of Oddi. Remifentanil is metabolized enzymatically throughout the body. Its context-sensitive half-time is 3-4 min. The effect of remifentanil on the sphincter of Oddi, is unknown. We studied, in six healthy adult volunteers, the effect of remifentanil on the flow of dye from the gall bladder into the duodenum. Control hepatobiliary imaging with 5 mCi of technetium-labeled derivatives of iminodiacetic acid was performed on each volunteer. The time from IV dye (radiopharmaceutical) injection until its appearance in the duodenum was determined by continuous scanning. Two weeks later, each volunteer received remifentanil, 0.1 microg x kg(-1) x min(-1) infused for 30 min IV before the same dose of technetium-labeled derivatives of iminodiacetic acid was injected, and for the time of their control scan plus 10 min after the injection. When the dye appeared in the duodenum, the total time from injection was compared with the control value. The time from stopping the infusion until the dye appeared in the duodenum was the "recovery time." Control scan time was 20.5+/-9.9 min (mean +/- SD; range 10-33 min). Total scan time during and after the remifentanil infusion was 50.3+/-17.3 min (range 30-81 min) (P < 0002). The recovery time was 19.8+/-12.4 min (range 5-40 min). We conclude that remifentanil delays the drainage of dye from the gall bladder into the duodenum, but the delay is shorter than that reported after other studied opioids. IMPLICATIONS: Radioactive dye was injected IV into healthy volunteers to determine the time it took for the dye to appear in the duodenum. This was repeated under the influence of a short-acting narcotic analgesic, remifentanil. Remifentanil caused a much shorter delay than previously reported after morphine or meperidine.     

Evaluation of abstracts submitted for the annual meeting of the German Neurosurgical Society 1999--unravelling a mystery

The evaluation for the abstracts submitted for the annual meeting of the German Neurosurgical Society together with the Swiss Neurosurgical Society in Munich 1999, is presented as it has developed during the meetings of the last years. 597 abstracts were reviewed by the 30 members of the review committee according to a 5 point grading system. Cut off for acceptance was a mean grading of 2.7 points. Abstracts better than 2.4 were accepted, abstracts worse than 2.7 were rejected. Experimental studies were judged slightly better than clinical studies: the mean grading of clinical and experimental studies was 2.55 +/- 0.5 vs. 2.72 +/- 0.6 (p < 0.02). All abstracts with a mean grading of 2.4-2.7 and a standard deviation > 1.0 were discussed in a meeting of the review committee. 353 abstracts were accepted. Some of the abstracts submitted for oral presentation had to be converted to poster presentations. Among others the decision was based on the grading of the abstract.     

Rate of alcohol metabolism; do not "correct" the beta 60 estimate for comparisons among ethnic groups

Many studies have attempted to "correct" or "refine" initial beta 60 estimates of the rate of alcohol metabolism. The present study, however, finds that such "corrections" may be in error and that beta 60 is the best estimate now available for comparisons of alcohol clearance among individuals or ethnic groups.     

The clinical efficacy of single morning doses of levodopa methyl ester: dispersible Madopar and Sinemet plus in Parkinson disease.

For many patients with Parkinson disease and levodopa-related motor fluctuations, the latency to onset of action of a single dose of a levodopa preparation may be both long and variable. In an effort to find a more rapidly acting and reliable preparation of levodopa, we therefore studied the efficacy of single doses of an oral solution of 250 mg of levodopa methyl ester (ME) with benserazide, 50 mg and of a molar equivalent dose of dispersible Madopar (DM) (50/200) in 13 patients in the fasting state after overnight drug withdrawal. The response of seven of these patients was compared to that after two Sinemet 25/100. The latency to "on" was equally fast with ME and DM, and significantly faster than after standard Sinemet. The duration of "on" was similar with all three. Because of this more rapid relief of "off" periods, both ME and DM offer a potential clinical advantage over standard preparations of levodopa.     

The clinical efficacy of oral levodopa methyl ester solution in reversing afternoon "off" periods in Parkinson's disease

We compared the efficacy of a single dose of an oral solution of levodopa methyl ester (ME) to that of standard levodopa, in the form of a single dose of Madopar, in reversing afternoon "off" periods in 12 patients with Parkinson's disease (PD). The highly soluble ME solution led to a significantly more rapid reversal of "off" periods. This preparation may therefore convey a clinical advantage in patients experiencing motor fluctuations whilst taking multiple daily dosages of levodopa, particularly in those with long or highly variable latency to the next "on" period.     

Use of replicating oncolytic adenoviruses in combination therapy for cancer.

Oncolytic virotherapy is the use of genetically engineered viruses that specifically target and destroy tumor cells via their cytolytic replication cycle. Viral-mediated tumor destruction is propagated through infection of nearby tumor cells by the newly released progeny. Each cycle should amplify the number of oncolytic viruses available for infection. Our understanding of the life cycles of cytolytic viruses has allowed manipulation of their genome to selectively kill tumor cells over normal tissue. Because the mechanism of tumor destruction is different, oncolytic virotherapy should work synergistically with current modes of treatment such as chemotherapy and radiation therapy. This article focuses on oncolytic adenoviruses that have been created and tested in preclinical and clinical trials in combination with chemotherapy, radiation therapy, and gene therapy.