Skeletal muscle metabolism in two Pavulon treated tetanus patients

In two patients with severe tetanus the skeletal muscle metabolism was studied. Muscle biopsies were taken 4-6 weeks after the development of tetanus. The patients were treated during this time with a neuromuscular blocking agent. In one of the patients a biopsy was also taken before treatment, 2 days after the first symptoms of the disease. Enzyme activities representative for glycogen synthesis, glycogen greakdown, glycolysis, fatty acid beta-oxidation and respiratory chain, and fluxes of glucose, palmitate and leusine in vitro, and the concentrations of glycogen, triglycerides, phospholipids, cholesterol, proteins and RNA were determined in the muscle tissue. The enzyme activities in the muscle tissue examined 2 days after the development of tetanus were close to normal, excep for decreased activities of phosphofructokinase and glycogen synthase. After 4-6 weeks of treatment the fluxes of glucose and palmitate and the corresponding enzyme activities were low in both patients. These findings are consistent with muscular inactivity. In contrast the activity of glucose-6-phosphate dehydrogenase, the incorporation rate of leucine-carbon into proteins and the RNA content were high, indicating a high protein synthesis as a probable manifestation of active repairative processes. It is concluded that the skeletal muscle metabolism in these patients was affected in a degenerative manner and that this effect was attributed more to the treatment than to the disease per se. Dynamic physical training under supervision is recommended for the period after the generalized spasms to overcome the "disuse" effects in the skeletal muscles.     

Platelet aggregation measured by the screen filtration pressure method in hypertensive patients

In this study platelet aggregation was measured by the screen filtration pressure method in 2 groups of hypertensives separated according to age. They were perfectly matched for levels of various "risk factors", with normotensive "controls". No significant difference in platelet aggregate filtration pressure (PAFP) was found between hypertensives and normotensives. Contrary to normotensive subjects, there was no significant increase in the PAFP values with age in the hypertensives. This might be due to the significantly higher blood urea values in the hypertensives as compared to the normotensives. An inverse relationship between blood urea concentration and PAFP values was in fact confirmed by in vivo and in vitro studies.     

Four examples of subsurface uses in Finland

The paper provides a perspective on recent underground space developments in Finland by describing four case histories: (1) Helsinki's utility tunnel system; (2) development of the area around Kaisaniemi Metro Station; (3) the research halls of the Technical Research Centre of Finland; and (4) a model of an earth-sheltered house.     

Use of inpatient hospital services by people aged 90-99 years

OBJECTIVE: To examine the use of inpatient hospital services by people aged 90-99 years. DESIGN: Retrospective case note review. SETTING: Flinders Medical Centre, a 516-bed university teaching hospital in Adelaide, South Australia. PATIENTS: All patients aged 90-99 years on the separation register for 1995. MAIN OUTCOME MEASURES: Patient demographic characteristics, principal diagnosis, length of hospital stay and outcome, including destination at discharge. RESULTS: In 1995, 317 separations involved 214 patients aged 90-99 years; 148 patients (69%) were admitted to hospital once, 43 (20%) twice and 23 (11%) three times or more. In 54% of separations, patients came from the community, and these were less likely to be emergency admissions (72%) than were admissions from hostels (87%) and nursing homes (93%). Patients had a wide range of acute medical and surgical problems and a median of five documented comorbidities. Patients survived to leave hospital in 290 separations (91%) and returned directly to their previous living circumstances in 212 (67%). Median hospital stay was 5.0 days, and in 25% of separations stay was one day or less. Patients admitted under the care of geriatricians had more emergency admissions (98%) and longer mean hospital stays (8.9 days) than those admitted under surgeons (69%; 5.9 days) or other physicians (66%; 5.0 days). CONCLUSION: Despite the acute nature of their illnesses and their multiple medical problems, most hospitalised nonagenarians in this study returned directly to their previous living circumstances after short hospital stays.     

Clearance of postprandial and lipolytically modified human HDL in rabbits and rats

Triglyceride (TG) enrichment of high density lipoproteins (HDL) in hypertriglyceridemic states renders the particles vulnerable to lipolysis, which reduces their size. In the present study we modified the size and composition of HDL in vivo in hypertriglyceridemic humans by administering a bolus of intravenous heparin, and tested the subsequent clearance of the isolated HDL particles in rabbits and rats. HDL was isolated by ultracentrifugation from 21 moderately hypertriglyceridemic humans, 5 h after ingestion of a high fat meal and then 15 min after an intravenous heparin bolus (60 U/kg). Postprandial large TG-rich preheparin HDL and small, TG-poor postheparin HDL were labeled with either 125I or 131I. The clearance of apoA-I associated with each HDL tracer was determined by injecting the tracers 1) simultaneously (n = 13) and 2) sequentially (n = 8) into male New Zealand White rabbits, an hepatic lipase-deficient animal, and 3) by injecting the tracers simultaneously into male Sprague-Dawley rats (n = 8), an animal that has hepatic lipase. Die-away curves of each radiolabeled tracer were analyzed using a two-pool model that assumes the existence of an intravascular pool in dynamic equilibrium with an extravascular pool. In the rabbit studies, the fractional catabolic rate (FCR) of small, postheparin TG-poor HDL was greater than the FCR of the larger TG-rich HDL (11% greater in the simultaneous study, P < 0.001, and 45% greater in the sequential study, P < 0.001). Opposite results were observed in rats as large TG-rich preheparin particles showed a greater FCR (1.8-fold) than smaller TG-poor postheparin HDL (P < 0.05). These data suggest that although size and composition of HDL can influence its catabolism, the effect is not always in the same direction and depends on other factors present in vivo.     

Age-related macular disease in rural southern Italy

OBJECTIVE: To report the prevalence of age-related maculopathy (ARM) in Salandra, a small, isolated southern Italian community, to test the hypothesis that an environmental factor, scarce in such a remote community but ubiquitous in modern industrial societies, might modify the risk of developing ARM. DESIGN: Population-based cross-sectional survey. MAIN OUTCOME MEASURES: Prevalence of advanced age-related macular degeneration (ARMD) (geographic atrophy or exudative maculopathy) and ARM (large, soft drusen or retinal pigment epithelium changes, or both) defined by fundus biomicroscopy and 30 degrees stereoscopic, macular photography. Self-sustenance was assessed by interview of participants and local shop retailers. The degree of genetic isolation was computed using a model that fits the genetic population structure with the frequency distribution of surnames in the community. RESULTS: A full ophthalmic examination was undertaken in 366 (63.5%) of 576 eligible participants, 354 (96.7%) of whom had clinical or photographic assessment for the presence of ARMD and 310 (84.6%) of whom had drusen characteristics graded on color transparencies for ARM. The overall prevalence of ARMD was 1.1%. Drusen larger than 50 microns and more numerous than 10 were found in 4.5% of subjects. Salandra was the birthplace of 87.2% of participants and for 77.3% of both parents of each subject. People in the community tended to consume homegrown products. CONCLUSION: The prevalence of ARM may be lower in this self-sustained farming community than elsewhere in the industrialized world.     

Immune responses associated with chronic fatigue syndrome: a case-control study

MR images of the liver in 13 patients with surgically proven intrahepatic cholangiocarcinoma were reviewed retrospectively and correlated to the histologic analysis of surgical specimens. We paid special attention to the peripheral liver tissue with ductal dilation but without tumorous involvement. High signal intensity was observed in the hepatic parenchyma with ductal dilation on T1-weighted spin-echo images (8 of 12) and spoiled gradient-recalled echo images (seven of seven), as compared with the contralateral hepatic lobe without duct dilation. The high signal intensity was not suppressed with fat saturation and showed enhancement after administration of contrast (11 of 12). Concurrent portal venous obstruction did not have significant effect on these findings (P < .05). Correlation with pathologic specimens suggested that this enhancement was associated with periportal fibrosis. The etiology of the high signal intensity on unenhanced spin echo or gradient-recalled T1-weighted image remains unclear. Radiologists should recognize these findings and should distinguish these from tumor involvement or the arterial buffer response caused by portal venous obstruction.     

Immunologic protection afforded by sunscreens in vitro

Several studies have suggested a lack of correlation between sunscreen sun protection factor and protection of the skin immune system, potentially allowing greater damage to the skin by removing the natural protective erythemal response to sun exposure. Despite this, routine testing of immune protection afforded by sunscreens is not performed by industry. Current laboratory methods for investigating the efficacy of sunscreen protection of epidermal immune function use the induction of contact hypersensitivity or epidermal cell alloantigen presentation. Animal models, cell culture systems, and in vivo human studies are commonly employed, but all these systems have significant drawbacks for use in routine testing. The purpose of this study was to develop an in vitro system for testing the immunologic protection afforded by sunscreens in human skin. Five test sunscreens plus a vehicle control were tested in a "blind" fashion for their in vitro level of immune protection. Creams were applied in a standard manner to human whole skin explants and were irradiated over a range of physiologic doses using an Oriel solar simulator. A mixed epidermal lymphocyte reaction was used to quantify epidermal alloantigen-presenting capacity, in the presence or absence of test cream, for five explants. Results consistently demonstrated that all the test sunscreens protected beyond their designated sun protection factors, whereas the vehicle conferred no protection. The explant-mixed epidermal lymphocyte reaction system gave consistent, reproducible results and may prove useful for the allocation of an immune protection factor to all sunscreens.     

Identification of the amino terminus of neuronal Ca2+ channel alpha1 subunits alpha1B and alpha1E as an essential determinant of G-protein modulation

We have examined the basis for G-protein modulation of the neuronal voltage-dependent calcium channels (VDCCs) alpha1E and alpha1B. A novel PCR product of alpha1E was isolated from rat brain. This contained an extended 5' DNA sequence and was subcloned onto the previously cloned isoform rbEII, giving rise to alpha1Elong whose N terminus was extended by 50 amino acids. VDCC alpha1 subunit constructs were co-expressed with the accessory alpha2-delta and beta2a subunits in Xenopus oocytes and mammalian (COS-7) cells. The alpha1Elong showed biophysical properties similar to those of rbEII; however, when G-protein modulation of expressed alpha1 subunits was induced by activation of co-expressed dopamine (D2) receptors with quinpirole (100 nM) in oocytes, or by co-transfection of Gbeta1gamma2 subunits in COS-7 cells, alpha1Elong, unlike alpha1E(rbEII), was found to be G-protein-modulated, in terms of both a slowing of activation kinetics and a reduction in current amplitude. However, alpha1Elong showed less modulation than alpha1B, and substitution of the alpha1E1-50 with the corresponding region of alpha1B1-55 produced a chimera alpha1bEEEE, with G-protein modulation intermediate between alpha1Elong and alpha1B. Furthermore, deletion of the N-terminal 1-55 sequence from alpha1B produced alpha1BDeltaN1-55, which could not be modulated, thus identifying the N-terminal domain as essential for G-protein modulation. Taken together with previous studies, these results indicate that the intracellular N terminus of alpha1E1-50 and alpha1B1-55 is likely to contribute to a multicomponent site, together with the intracellular I-II loop and/or the C-terminal tail, which are involved in Gbetagamma binding and/or in subsequent modulation of channel gating.