Metabolic abnormalities in obese patients with impaired glucose tolerance

It is not clear whether the glucose tolerance test diagnosis of Impaired Glucose Tolerance introduced in the recent revisions of diagnostic criteria is associated with abnormalities of intermediary metabolism other than glucose. Intermediary metabolite concentrations have therefore been studied fasting and in response to oral glucose in 35 patients referred with morbid obesity accompanied by either normal glucose tolerance (18 patients) or Impaired Glucose Tolerance (17 patients). When fasting obese patients with Impaired Glucose Tolerance had significantly higher blood total ketone body concentrations, 0.24 (0.19-0.30) vs 0.14 (0.12-0.16) mmol l-1 (antilog of mean-SE to mean + SE) (p less than 0.05), and lower blood glycerol concentrations, 0.14 +/- 0.01 vs 0.18 +/- 0.01 mmol l-1 (mean +/- SE) (p less than 0.05), than obese patients with normal glucose tolerance. There were no significant differences in fasting insulin, 16 (15-18) vs 14 (12-15) mU l-1, or glucose levels, 5.3 +/- 0.2 vs 5.1 +/- 0.2 mmol l-1. After oral glucose there was an exaggerated rise in glucose, insulin, lactate, and pyruvate in patients with Impaired Glucose Tolerance.     

An alternative method of vascular anastomosis by laser: experimental and clinical study

In vascular surgery, it is now very difficult to maintain the long-term patency after a conventional vascular anastomosis, especially for small-caliber vessels. A low-energy CO2 laser was experimentally employed to make a vascular anastomosis with only a few sutures. Subsequently, it could be confirmed that optimal conditions for vascular anastomosis by laser were 20-40 mW in output and 6-12 sec/mm in irradiation time. On the other hand, pressure tolerance test as well as tensile strength test and microscopic examinations at the sites of anastomoses by laser were compared with the conventional suture method. There were no significant differences between laser and suture methods. On the basis of the excellent results of this study, the laser was clinically applied for anastomoses of the peripheral vessels in 35 patients. The first clinical laser application in the world was successful in a 44-year-old female patient with chronic renal failure in 1985. All patients are doing well without any complications from vascular anastomosis by laser. From these experimental and clinical studies, it can be concluded that anastomosis by laser should be recommended for small-caliber vessels such as aortocoronary bypass surgery.     

Effects of D-Met2, Pro5-enkephalinamide on pain tolerance and some cognitive functions in man

The effects ofd-Met², Pro⁵-enkephalinamide (EA) on pain tolerance and some cognitive functions have been examined in healthy male volunteers. Dihydrocodeine (DC) was used as reference substance. Applying the submaximum effort tourniquet technique EA (10 mg SC) was found to elevate the pain threshold similarly to DC (20 mg SC). Neither DC nor EA impaired the performance in the symbol cancellation test, which quantitates the intensity of attention. In this assay rather a slight improvement was detected. In addition the short-term memory performance (Wechsler test) was also improved by EA and DC. No alteration was seen in the word fluency test, an indicator of long-term (semantic) memory. The data show that EA not only improves pain tolerance but some of its mental effects are similar to those of a classical morphine congener DC.     

Evidence that genetic differences in habituation and GABAergic mechanisms may be related to sensitivity to ethanol and development of ethanol tolerance in mice

Habituation to a test environment following daily exposure for 5 days was examined in three genetically different strains of mice. C57 animals showed significant habituation to the new environment already on the second day. The habituation of NMRI mice was significant on the third day, whereas CBA mice showed no habituation at all during the experimental period. There was no difference between the animal strains in learning capacity in a passive avoidance test, but CBA mice displayed a significant increase in latency in their performance. When tested for sensitivity to the convulsant actions of GABAergic antagonists, picrotoxin produced seizures at lower doses in CBA as compared to NMRI and C57 mice, whereas there was no difference between the strains in the seizure activity produced by the specific GABA receptor antagonist bicuculline. When the animals were tested for sensitivity to ethanol in a horizontal wire test, ethanol (2 g/kg, IP) produced muscle relaxation in CBA mice whereas the performance of NMRI and C57 was not affected. A large dose of ethanol (4 g/kg, IP) produced a significantly longer sleeping time in CBA mice as compared to NMRI and C57 animals. Ethanol-produced hypothermia was, however, similar in all animals. Environment-dependent development of tolerance to ethanol following daily injections of ethanol for 4 days was examined. C57 mice showed the most rapid development of tolerance towards ethanol's hypnotic actions, whereas CBA mice showed no tolerance to this effect of ethanol. No difference between the strains to the development of tolerance to ethanol's hypothermic effects was observed. The present findings indicate that sensitivity to ethanol and ethanol tolerance are complex phenomena which cannot be adequately characterized by measuring only one single functional response to ethanol. The possibility that a genetically determined perturbation in the functions of the GABA receptor-coupled chloride channel, noted as variable sensitivity to picrotoxin, may be of importance for the observed disturbance in habituation to a new environment, for the different sensitivity to ethanol, and for the different rate of development of ethanol tolerance is discussed.     

Effects of four orally administered analogues of prostaglandin E1 and E2 on glucose tolerance and on the secretion of pancreatic and gastrointestinal hormones in man

Oral glucose tolerance tests (75 g, 300 ml) were performed in 12 healthy volunteers, with prior administration of placebo, misoprostol (400 micrograms), rioprostil (300 micrograms), enprostil (70 micrograms), or nocloprost (200 micrograms), in a double-blind, randomized manner. None of the drugs significantly affected glucose tolerance, although with misoprostal some volunteers displayed an impaired glucose tolerance. Nocloprost was without effect on gastric inhibitory polypeptide (GIP) and did not influence insulin or C-peptide concentrations. Misoprostol and rioprostil reduced integrated incremental responses of GIP by 57% (P less than or equal to 0.001) and 45% (P less than or equal to 0.01), respectively, and both gave rise to an initial (approximately 10 min) delay of insulin and C-peptide responses, without a significant overall reduction in integrated incremental responses. Enprostil almost totally inhibited the GIP response (by 94%; P less than or equal to 0.001), delayed initial insulin and C-peptide responses, but reduced the integrated incremental C-peptide response (which corresponds to the overall release of insulin) by only 14% (P less than or equal to 0.05). Enprostil more substantially reduced the integrated incremental response of insulin by 36% (P less than or equal to 0.01), and also reduced the ratio of insulin and C-peptide incremental responses (P less than or equal to 0.001). In conclusion, prostaglandin E analogues which caused a reduction in GIP responses, and thereby disrupting the enteroinsular axis to varying degrees, delayed the time-course of insulin secretion without a significant impact on glucose tolerance.(ABSTRACT TRUNCATED AT 250 WORDS)     

Airway inflammation induced after allergic poly-sensitization can be prevented by mucosal but not by systemic administration of poly-peptides

Background Patients with multiple sensitizations require alternative forms of treatment, as the efficacy of conventional immunotherapy is unsatisfactory. Objective In the present study, we sought to compare the efficacy of a subcutaneously (s.c.) and a mucosally applied polyvalent vaccine to reduce allergic immune responses within airway and lung tissues. Methods Female BALB/c mice were intraperitoneally immunized with recombinant (r)Bet v 1, rPhl p 1 and rPhl p 5, followed by an aerosol challenge of birch and phleum pollen extract. For tolerance induction, either a mixture of the immunodominant peptides or a hybrid peptide of the respective antigens was s.c. injected or intranasally applied before poly‐sensitization. Results Mucosal but not systemic pre‐treatment with poly‐peptides led to significant suppression of eosinophils and IL‐5 production in bronchoalveolar lavages, as well as IL‐5, IL‐4, IL‐13 and eotaxin levels in lung cell cultures. Lung histology showed a clear reduction of cellular infiltration and mucus production only in intranasally pre‐treated mice. In accordance, also the systemic immune response, characterized by IgE‐dependent basophil degranulation and IL‐4 levels in vitro, was significantly reduced by mucosal antigen application, but only marginally influenced by subcutaneous pre‐treatment. Both treatment routes led to up‐regulated CTLA4 expression in splenocytes, whereas only after mucosal pre‐treatment Foxp3 expression levels were enhanced in lung CD3⁺ T cells. Furthermore, intranasal but not subcutaneous application of the peptides enhanced IL‐10 levels in the lungs, indicating regulatory mechanisms operating in local tolerance induction. Conclusion Mucosal application of peptides is superior to systemic application in preventing both local and systemic poly‐allergic T helper2 immune responses, suggesting mucosal tolerance induction as an attractive strategy for the primary and secondary prevention of allergic multi‐sensitization and lung pathology.     

Predicted Dose-Volume Isoeffect Curves for Stereotactic Radiosurgery with the 60Co Gamma Unit

Mathematical models were developed to predict tolerance of brain tissue to stereotactic radiosurgery. the use of these formulas for predicting symptomatic brain necrosis from stereotactic radiosurgery with the Co gamma unit is discussed. Predicted dose-response curves for different collimator sizes were calculated. Dose-volume isoeffect curves for a 3% risk of brain necrosis from a single fraction radiosurgery were then derived. Dose-volume isoeffect curves for combinations of fractionated whole brain irradiation with radiosurgery boosts were also calculated. the predicted dose-volume isoeffect curves provide useful tolerance guidelines for the practice of stereotactic radiosurgery.     

加压呼吸与对抗动作联合抗荷效果的研究

本文介绍了研究胸部有代偿加压呼吸(APPB)与L-1对抗动作的生理效应及二者联合应用的可能性与抗荷效果。根据实验中不同余压值APPB的心血管效应及被试者主观反应进行综合判定,我们认为,以APPB_(5.98)用于提高+Gz耐力较为合适。APPB_(5.98)的血压、心率、心输出量及预测G耐力均明显低于L-1动作(p<0.05),但比L-1动作省力和易于掌握。APPB_(5.98)与L-1动作的联合应用不仅是可能的,也是非常有效的。不论是否同时使用抗荷服,APPB_(5.98)+L-1动作的血压及预测G耐力均明显高于APPB_(5.98)及L-1动作单项措施,而且其疲劳程度与单纯使用L-1动作相比无明显差别。离心机试验结果表明,APPB_(5.98)+L-1动作+抗荷服(AGS)综合措施的抗荷效果为3.95G。飞行员实验结果表现出相同的趋势。     

Adequacy of haemodiafiltration

In this study we have evaluated the influence of blood and ultrafiltration flow rate on the performance of five different high-flux membrane dialysers during haemodiafiltration. On the basis of clearance data we optimised the haemodiafiltration schedule of six uraemic patients to maintain an adequate midweek blood urea nitrogen concentration, while reducing the treatment time from 285 +/- 23 min to 210 min. After a follow-up of 6 months, we observed no difference in the clinical tolerance or in the biochemical parameters, compared to those found during the preceding haemodialysis period. Our data confirm the suggestions of other authors that haemodiafiltration is an effective alternative to conventional haemodialysis.