Anti-ulcerogenic activity of GABA and GABA mimetic agents in rats

Erythropoietin, the hematopoietic growth factor, is synthesised in the kidneys and liver and regulates red blood cell production. Within the last few years, recombinant DNA technology has produced synthetic erythropoietin (rhEPO). Some patients, especially Jehovah's Witnesses, will not accept blood transfusion. The perioperative administration of rhEPO increases the patients' hematocrit (HCt) to a higher than physiological level. METHODS AND RESULTS: We report a case of a 66-year-old female Jehovah's Witness who refused blood transfusions and responded favourably to rhEPO treatment. A total hip arthroplasty was planned. A pretreatment hemoglobin level (Hb) of 13.7 g/dl and HCt of 43% were documented. After preoperative subcutaneous application of 5000 I.E. rhEPO three times per week and daily oral substitution of 300 mg ferrous sulfate over a period of 3 weeks, the Hb increased to 15.5 g/dl and the HCt to 49%. The operation was carried out after the ninth application of rhEPO. Postoperatively, the Hb concentration was 11.8 g/dl and the HCt 35%. Therefore, postoperative administration of rhEPO was not considered indicated. No side effects of rhEPO application were noted. The patient left hospital on the 10th postoperative day. CONCLUSIONS: The case report describes perioperative management using human rhEPO in Jehovah's Witnesses. Treatment with rhEPO increases preoperative Hb levels to a point making it possible to compensate for operative blood loss. RhEPO combined with daily iron substitution may be useful in patients who refuse transfusion based on religious convictions.     

Oxygen tension profiles in isolated hamster retractor muscle at different temperatures

Oxygen tension (P0(2)) profiles within unperfused hamster retractor muscles were obtained at 25, 30, and 37 degrees by using sharpened, recessed oxygen microelectrodes. The microelectrode was driven vertically into freshly excised muscle lying on a flat, impermeable boundary inside a diffusion chamber. Intramuscular P0(2) profiles were measured as a function of electrode depth in 10-mu m steps during both inward and outward penetrations when the upper surface of the muscles was exposed to humidified gases containing 10, 21, 50, and 100% 0(2). The ratio of the 0(2) consumption (M) to the 0(2) permeability (K, Krogh diffusion coefficient = D alpha, diffusion coefficient-solubility product) was estimated by curve-fitting the experimental steady-state distribution of 0(2) through muscles to the analytic solution of the diffusion equation assuming that M obeys zero-order kinetics and K is constant, uniform, and independent of P0(2). The ratios of M/K were independent of temperature and were found to be independent of surface P0(2) and muscle thickness. The average value of M/K was 3.9 +/- 0.45 (SE; n = 30) x 10(5) mm Hg/cm(2), which is consistent with that estimated from previous measurements of M and D using different non-steady-state techniques (Bentley et aL, 1993). These results are consistent with other in vitro 0(2) consumption measurements (Sullivan and Pittman, 1984) and do not provide evidence for nonclassical respiratory activity in resting mammalian skeletal muscle.     

Arachnoid cysts associated with post-traumatic and spontaneous rupture into the subdural space

61 children were studied and treated between January 1986 and September 1993 for idiopathic varicocele. The aim of our study was to evaluate the advantages and disadvantages of the different techniques and to show the progression to a greater efficacy. The mean age at the time of therapy was 14 years, ranging from 7 to 16 years. All children presenting with pain or testicular asymmetry were treated. Four asymptomatic children were followed for 2 years before treatment. 36 children were treated by surgical ligature via the inguinal approach; 8 with a resection of the varicose veins as far as the tunica vaginalis. 14 children were treated by percutaneous sclerotherapy including 1 patient following unsuccessful classical surgical treatment. 12 children were treated by surgical inguinal ligature associated with peroperative phlebography and thrombosis. 56 children were reviewed postoperatively over a period which varied from 2 months to 4 years (5 lost to follow-up). For the 36 classical ligatures: 25 good results, but 9 hydroceles (5 out 8 varicose resections): 70% good results. 7 failures and 4 lost to follow-up. For the 14 percutaneous sclerotherapy: 4 technical failures (impossibility to catheterize the spermatic vein): 10 good results. For the 12 ligatures with peroperative phlebography and thrombosis: 11 good results and 1 lost to follow-up. All the above procedures were carried out at our out-patient clinic. The therapeutic choice will therefore have to take into consideration a procedure which produces the lowest morbidity rate and proves to be the most effective. The association of surgical ligature, phlebography and thrombosis meets these requirements.     

Procedures for mastitis diagnosis and control

Procedures for mastitis diagnosis and control include culturing individual cow and bulk tank milk samples, antibiotic susceptibility testing, and evaluation of somatic cell count reports and clinical mastitis treatment records. Integrated use of such procedures is necessary for effective mastitis diagnosis and control.     

Serological and immunogenetic markers of extraglandular primary Sj?gren's syndrome

The clinical course of 48 patients with primary Sj?gren's syndrome (primary SS) was reviewed. Forty-three north European patients were typed for HLA class I and class II alloantigens. In this population with primary SS HLA B8, DR3 and DRw52 all occurred more frequently than in the control population (P < 0.009, P < 0.0035, P < 0.02 respectively). The subgroup of primary SS patients with antibodies to Ro and/or La antigen had the greatest prevalence of DR3 (relative risk 33.4). The primary SS patients fall into two distinct groups: those with extraglandular disease in whom lymphopaenia, hypergammaglobulinaemia, antibodies to Ro and/or La and HLA DR3 were all more frequent and those patients with either glandular disease alone or only one extraglandular feature. There was no difference in disease duration between the two groups, although on average the latter group were 10 years older.     

Modulation of thrombin-induced platelet aggregation by inhibition of calpain by a synthetic peptide derived from the thiol-protease inhibitory sequence of kininogens and S-(3-nitro-2-pyridinesulfenyl)-cysteine

Thrombin-induced platelet aggregation has been suggested to play an important role in reocclusion following thrombolytic therapy of angioplasty for treatment of myocardial infarction. We previously demonstrated that aggregation of washed platelets by thrombin is accompanied by cleavage of aggregin, a putative ADP receptor, and that these events are indirectly mediated by calpain, expressed on the surface of the external membrane. High-molecular-mass kininogen (HK) contains, in its heavy chain, domain 2, which is responsible for its action as a potent inhibitor of platelet calpain. Domain 3 of the heavy chain of HK directly inhibits binding of thrombin to platelets, confounding mechanistic studies using the entire molecule. Moreover, HK, a protease of 120 kDa, is unsuitable as a potential pharmacological agent. The highly conserved sequence Gln-Val-Val-Ala-Gly, present in HK and its evolutionary precursors, the cystatins, is thought to be involved in the binding of cysteine proteases but is, itself, not inhibitory. An affinity analog, Phe-Gln-Val-Val-Cys(Npys)-Gly-NH2(Npys, 3-nitro-2-sulfenylpyridine), P1, corresponding to the thiol-protease-binding sequence in HK and containing a ligand, Npys, that can react with the free sulfhydryl group in the active site of calpain, was synthesized. P1 was an irreversible inhibitor of platelet calpain. P1 selectively inhibited thrombin-induced aggregation of washed platelets and platelets in plasma, but did not inhibit the aggregatory effects of other platelet agonists. P1 did not inhibit the amidolytic activity and coagulant activity of thrombin. Unlike HK, P1 did not inhibit binding of thrombin to washed platelets. P1 did not inhibit thrombin-induced platelet-shape change. P1 neither raised intracellular levels of cAMP nor did it interfere with the ability of thrombin to antagonize the rise in intracellular levels of cAMP induced by iloprost, an analog of prostaglandin I2. The design and synthesis of P1 could leave to the development of a new class of inhibitors that selectively block thrombin-induced platelet aggregation while sparing other functions of this pathophysiological protease and without inhibiting the action of other platelet agonists.