Platelet function during continuous insulin infusion treatment in insulin-dependent diabetic patients

Patients with diabetes mellitus manifest increased in vitro platelet aggregation and increased synthesis of the proaggregant and vasoconstrictor, thromboxane A2 (TXA2). We studied the effects of continuous insulin infusion treatment on platelet aggregation and arachidonic acid (AA)-stimulated platelet TXA2 synthesis (15 and 30 s post-AA, 1 mM) in 16 type I diabetic patients. Strict glycemic control was induced with the Biostator for 2 days and maintained for 12-14 days with continuous subcutaneous insulin infusion (CSII). The average premeal plasma glucose level (4/day) fell from 184 +/- 15, before treatment, to 107 +/- 6 mg/dl on the final day (P less than 0.001). After control, platelet synthesis of TXA2, measured by radioimmunoassay of its stable metabolite, immunoreactive TXB2 (iTXB2), decreased in all patients (30 s: 276 +/- 31 versus 199 +/- 28 ng iTXB2/ml/5 X 10(5) platelets; P less than 0.05). The reduction in platelet iTXB2 synthesis (15 and 30 s) was greater in poorly controlled patients (HbA1c greater than 12%; N = 8), and for all patients the decrease in iTXB2 (15 and 30 s) was correlated with the prestudy HbA1c level (15 s: r = 0.6; P less than 0.01). In contrast, platelet aggregation responses did not improve during intensive insulin treatment. The ED50 for AA (dose producing 50% maximum aggregation at 1 min) was unchanged after 2 wk of treatment and the ED50 for aggregation induced by ADP fell significantly in patients with HbA1c greater than 12% (2.8 +/- 1.3 versus 1.2 +/- 0.6 microM; P less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)     

自身免疫甲状腺病循环和甲状腺内细胞毒性T细胞(T_8/S_6F_1)的实验研究

应用新型单克隆抗体T_8/S_6F_1和流体细胞测定仪双色荧光程序检测了15例Graves病和8例Hashimoto甲状腺炎患者循环和甲状腺内的细胞毒性T细胞(cytotoxic T ceils,Tc)的分布。传统的单克隆抗体CD_8(OKT_8或Leu_2)仅能检测含有两个次亚群——抑制性T细胞(Ts)和细胞毒性T细胞(Tc)的Ts/TcT细胞亚群,不能将它们区别开来。本文应用的单克隆抗体T_8/S-6F_1首次能够单独测定Tc亚群。Graves病和Hashimoto甲状腺炎患者的循环Tc亚群分别为27.6±11.2％和27.5％±12.2％,与正常对照组差异无显著性。两组患者甲状腺内的Tc亚群数目也未见增加。Graves病患者甲状腺内Te细胞为16.45±4.7％。本文结果提示:AITD患者循环内和甲状腺内的细胞毒性T细胞亚群的数目未见增加。     

Bone matrix stimulates osteoclastic differentiation in cultures of rabbit bone marrow cells

Cells showing osteoclastic characteristics have not been identified outside bone. Because osteoclasts originate from an extraosseous source, this suggests that identifiable osteoclastic features do not develop until the precursors enter bone, where the local microenvironment may signal osteoclastic differentiation or maturation. We assessed the influence of bone matrix on osteoclastic differentiation by incubating bone marrow cells, after removal of pre-existing osteoclasts, on plastic coverslips or slices of devitalized cortical bone. We found that there was a threefold increase in the number of osteoclast-specific MAb-positive cells on the bone matrix compared with plastic coverslips. The number of MAb-positive cells correlated with the extent of excavation of the surface of the bone slices. Multinuclearity correlated with MAb-positive cell density, and for any given density the proportion of MAb-positive cells that were multinucleate was similar on plastic and bone. We conclude that, in the presence of 1,25-(OH)2 vitamin D3, bone matrix stimulates the generation of osteoclasts but has no demonstrable influence on the fusion of mononuclear osteoclastic precursors.     

Echography and pulsed Doppler of the arteries of the renal parenchyma in obstructive syndromes and dilatation of the excretory cavities of the kidney

Ultrasonography is highly effective in diagnosing pyelocalyceal dilatation. Confirming the distension of these collecting structures, indicating probable obstruction, is more difficult since the degree of dilatation does not always correspond to the degree of distension. Renal studies were performed in 244 patients including 51 patients with dilation or renal obstruction. Doppler ultrasonography was used to measure the Pourcelot's resistive index of arcuate and interlobar arteries for each kidney. Results demonstrate: 1) for healthy patients the average vascular resistive index is 0.54 +/- 0.02 (minimum 0.48 +/- 0.02, maximum 0.60 +/- 0.02). 2) in cases of acute obstruction, this resistive index for pathologic kidney is elevated greater than 0.7. The difference in resistive indices between the pathologic and contralateral kidney was greater than 0.10. 3) in the patients with intermittent junctional syndromes when an intravenous furosemide test is used, there is an increase in the resistive index. 4) in case of chronic obstruction well tolerated, the increase in resistive index is moderate. If there is an acute deterioration, the resistive index become greater than 0.8. Concurrent abnormalities which affect only one kidney (pathology of the renal hilum, tumoral syndromes) may make it difficult to interpret certain results. Ultrasonography together with Doppler scanning may be in certain cases a reasonable alternative with IVP.     

The pharmacokinetics and pharmacodynamics of adinazolam: multi-ethnic comparisons

The pharmacokinetics and pharmacodynamics of adinazolam and N-demethyladinazolam (NDMAD), its major active metabolite, were compared in 39 healthy male volunteers (13 Asian, 12 Caucasian and 14 African-American). In a four-way, double-blind crossover design, subjects were administered (1) 30 mg oral adinazolam mesylate SR tablets, (2) 10 mg parenteral (IV) adinazolam mesylate, (3) 30 mg IV NDMAD and (4) placebo. Venous blood samples were collected at specific time intervals after drug administration and assayed for adinazolam and NDMAD concentrations. Sedation was rated at the time of each blood draw according to the Nurse-Rated Sedation Scale, and the digit-symbol substitution test was administered to evaluate psychomotor performance. After IV administration of adinazolam, Asians manifested significantly higher C_max, larger AUC and lower CL of both adinazolam and NDMAD than their Caucasian and African-American counterparts. Likewise, after IV NDMAD Asians had significantly higher NDMAD C_max and AUC than Caucasians and African-Americans. Most of these differences remained statistically significant after controlling for body surface area. With PO adinazolam, Asians also manifested substantially higher C_max, larger AUC and lower CL for both adinazolam and NDMAD; however, with the exception of C_max, these differences did not reach statistical significance. These results are in accordance with previous observations for ethnic-related differences in drug pharmacokinetics. In contrast, pharmacodynamic differences were not noted among the three study groups. Received: 19 June 1996/Final version: 17 September 1996     

A factor analytical study of tinnitus complaint behaviour

Two separate factor analyses were conducted on various self-rated complaints about tinnitus and related neuro-otological symptoms, together with audiometric measurements of tinnitus 'intensity' (masking level and loudness matching levels). Two general tinnitus complaint factors were identified, i.e. 'intrusiveness of tinnitus' and 'distress due to tinnitus'. 3 specific tinnitus complaint factors were also found, i.e. 'sleep disturbance', 'medication use' and 'interference with passive auditory entertainments'. Other neuro-otological symptoms and the audiometric measures did not load on these factors. An exception was provided by loudness matches at 1 kHz, which had a small loading on the 'intrusiveness of tinnitus' factor. Self-rated loudness had a high loading on this factor. Otherwise, the loudness (either self-rated or determined by loudness matching) was unrelated to complaint dimensions. The clinical implications of the multifactorial nature of tinnitus complaint behaviour are considered.     

Matched and self-reported loudness of tinnitus: methods and sources of error

A consecutive series of 62 patients who reported tinnitus at the time of their first attendance at a neuro-otology clinic were studied. Loudness matches were obtained both at the frequency of the tinnitus and at 1 kHz. These matches were expressed in dB HL, dB SL and in units derived from individualised loudness functions (personal loudness units; PLUs). Self-reports of the loudness of tinnitus at the time of loudness matching were obtained on five different scales. Moderate correlations were found between self-reported loudness and some of the scales by which the loudness match was expressed. When subjects who had some difficulty with the test procedures were excluded, the correlations between PLU expressions of the matched loudness and certain of the self-report scales were found to be markedly improved. Correlations of traditional expressions of matched loudness with self-report improved to a limited extent. It was concluded that: measurement error can appreciably reduce the maximum correlation between the best self-report measure and loudness match measures; PLU conversions of matched loudness data produce the highest correlations with self-report measures of loudness, and explicitly labelled self-report scales (Guttman and adjectival) produce better correlations with loudness match values than other self-report scales.