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11.
G C Palmer M L Stagnitto J M Ordy R C Griffith J J Napier R J Gentile J H Woodhead H S White E A Swinyard 《Epilepsy research》1991,8(1):36-48
Stereoisomers of remacemide (racemate form) were compared for anticonvulsant efficacy and safety in mice. In the maximal electroshock seizure (MES) test for oral efficacy, the (-) stereoisomer, FPL 14145, was more potent than the racemate or the (+) stereoisomer, FPL 14144. Respective ED50 values (expressed as mg/kg) were: remacemide, 58; FPL 14145, 45; FPL 14144, 79. In 2 of 3 tests for neural impairment, FPL 14145 yielded significantly better therapeutic indices (toxic dose 50/ED50) than the racemate. The margin of safety (estimated median lethal dose ED50) was more favorable for FPL 14144: remacemide, 15.1; FPL 14144, 18.9; FPL 14145, 15.7. The duration of protection against MES indicated the stereoisomers were longer acting than the racemate. After intravenous administration the order of potency against MES was similar: FPL 14145 greater than remacemide greater than FPL 14144. Following daily administration of the oral ED98 for 4 days, with a dose response curve run on day 5, the MES ED50 values for all compounds were increased. The test indicates tolerance. In the pentylenetetrazol infusion test the racemate and FPL 14144 demonstrated more proconvulsant properties than FPL 14145. Intraperitoneal administration of 50 mg/kg or more produced changes in behavior with all compounds. At higher doses the racemate and FPL 14145 elicited more severe symptoms with death at 200 mg/kg. 相似文献
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Nonprogression of subclinical beta-cell dysfunction among first-degree relatives of IDDM patients. 5-yr follow-up of the Seattle Family Study 总被引:4,自引:0,他引:4
D K McCulloch L J Klaff S E Kahn S L Schoenfeld C J Greenbaum R S Mauseth E A Benson G T Nepom L Shewey J P Palmer 《Diabetes》1990,39(5):549-556
It is unknown among first-degree relatives of individuals with insulin-dependent diabetes mellitus (IDDM) whether the disease process occurs in relatively few but always progresses to clinical IDDM or whether subclinical disease is more common but remains nonprogressive in many cases. Islet cell antibodies (ICAs) were found in 21 of 724 (2.9%) first-degree relatives during screening in the greater Seattle area between 1983 and 1988. Measures of beta-cell function (glucose disappearance rate [Kg], fasting insulin, acute insulin response to intravenous arginine [AIRarg], acute insulin response to intravenous glucose [AIRgluc], slope of glucose potentiation of AIRarg) and insulin sensitivity were obtained. Twenty individuals, 9 ICA+ relatives and 11 ICA- relatives, were evaluated prospectively. When expressed in relation to the expected AIRgluc based on each subject's sensitivity index, AIRgluc in 18 of 20 relatives fell below 100%, indicating inappropriately low insulin secretion (subclinical beta-cell dysfunction). After a median follow-up of 42 mo, 10 of 11 ICA- relatives remained ICA-. None showed deteriorating beta-cell dysfunction, and none developed diabetes. Five ICA+ relatives showed persistent immunologic positivity. beta-Cell function remained remarkably stable in all except 2 relatives. One was a 15-yr-old boy who developed IDDM shortly after screening and before evaluation of beta-cell function could be carried out. The other was an 18-yr-old monozygotic twin who developed IDDM after 27 mo. Both of these individuals had ICAs of 80 Juvenile Diabetes Foundation U and had been discordant for less than 5 yr.(ABSTRACT TRUNCATED AT 250 WORDS) 相似文献
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S C Gross H K Watson J W Strickland A K Palmer L H Brenner J Fatti 《The Journal of hand surgery》1989,14(1):95-102
Until recently the problem of painful, symptomatic arthritis of the wrist secondary to congenitally incomplete separation of carpal bones has been infrequently recognized. Five patients with either excessive stress loading or trauma had eight symptomatic wrists with congenitally incomplete separation of the triquetral-lunate joint. Three of these patients had bilateral symptoms. Six of the wrists had been treated by a limited wrist arthrodesis of the triquetral-lunate joint resulting in asymptomatic wrists and improved range of motion. It appears that patients with this congenital condition poorly tolerate stress loading or trauma secondary to deficient intra-articular cartilage formation resulting in a clinical and anatomic state similar to degenerative arthritis. We suggest a limited wrist arthrodesis as definitive treatment for symptomatic congenitally incomplete separation of the triquetral-lunate joint, with possible application in incomplete separation of the other intercarpal joints. 相似文献
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Rete testis fluid (RTF) and luminal fluid collected by micropuncture at selected epididymal sites were analyzed to characterize the spectrum of proteins and to quantify the net gain or loss of total/bulk protein and androgen-binding protein (ABP) between successive regions within the ductus epididymidis. Based on one-dimensional SDS gel electrophoresis, the spectra of proteins in RTF and fluids from the proximal, central, and distal caput through proximal corpus epididymidis differed from each other. Concentrations of sperm, bulk protein, and ABP increased from the rete testis through the central caput epididymidis. Electron microscopic studies following intraluminal microinjections of RTF proteins conjugated to colloidal gold at specific sites in the excurrent ducts revealed that 145 times more protein-gold was endocytosed in the ductuli efferentes than in any of the four regions of the caput epididymidis. Thus, ductuli efferentes were the major extra-testicular site of endocytosis of bulk protein present in RTF; at least a portion of the uptake was specific. On a per sperm basis, the amount of protein present in the central caput epididymidis was less than 15% of that leaving the testis. Although most of the protein present in RTF (greater than or equal to 86 mg/d) must be absorbed in the ductuli efferentes and the initial segment of the epididymis and replaced by newly secreted proteins (greater than or equal to 34 mg/d), there was negligible loss of ABP in these regions. Net loss of ABP occurred primarily in the distal caput and proximal corpus epididymidis. These studies demonstrate that ABP is spared from endocytosis along with the bulk protein in RTF and conserved for functions in epididymal regions far distal to the site of bulk protein loss. 相似文献