Drug-induced thrombocytopenia is associated with increased binding of IgG to platelets both in vivo and in vitro

Thrombocytopenia is a common serious adverse effect of drug treatment. A variety of in vitro diagnostic techniques to confirm the diagnosis are available, but the majority lack sufficient sensitivity to detect all cases of drug-induced thrombocytopenia. We studied 19 patients with suspected drug-induced thrombocytopenia and demonstrated that platelet- associated IgG (PAIgG) was elevated in all at the time of thrombocytopenia, and PAIgG returned to normal levels as the thrombocytopenia resolved. In the majority of patients, the platelet count rapidly returned to normal after the drug was discontinued; however, in six patients, the thrombocytopenia persisted well beyond the period of time that the offending drug would be expected to be cleared from the blood. In 13 patients, serum obtained after recovery was used to identify the drug responsible for the thrombocytopenia in an in vitro assay. In all cases, the addition of the drug historically associated with the thrombocytopenic episode was associated with an increased binding of IgG to control platelets. For uncertain reasons, the concentration of drug required to increase the in vitro binding of IgG to test platelets was often more than the concentration usually achieved in vivo. Wider application of these techniques may provide better understanding of the clinical characteristics and mechanisms responsible for drug-induce thrombocytopenia.     

Anti-factor VIII antibodies of hemophiliac patients are frequently directed towards nonfunctional determinants and do not exhibit isotypic restriction

A significant proportion of hemophilia A patients receiving transfusions of factor VIII (FVIII) develop a specific antibody response towards FVIII. These antibodies are usually detected by assays in which they inhibit the function of the molecule, such as the Bethesda clotting test. We have prepared anti-FVIII antibodies by specific immunoadsorption from the plasma of four hemophiliacs with stable inhibitor levels. The isotypic distribution of such antibodies was determined and their capacity to bind to insolubilized FVIII was compared with their inhibitory activity in two functional assays, namely, the Bethesda assay and a chromogenic assay. In addition, the FVIII epitope specificity was determined by competition with monoclonal antibodies for the binding to insolubilized FVIII. We show here that (1) anti-FVIII antibodies are not isotypically restricted; thus, a significant proportion of specific IgG2 was found; (2) antibodies are frequently directed towards epitopes of FVIII that are not directly involved in the function of the molecule and therefore escape detection in the Bethesda method or chromogenic assay; and (3) each patient shows a unique pattern of FVIII epitope recognition. We conclude that evaluation of anti-FVIII antibodies by a functional method does not provide an accurate evaluation of the specific antibody response. These findings have important implications for the comparison of the immunogenicity of FVIII molecules produced by different technologies and for the development of methods to control anti-FVIII antibody production.     

Quality index for the quantification of the information recorded along standard microelectrode tracks to the subthalamic nucleus in parkinsonian patients.

OBJECTIVE: To quantify the usefulness of the neuronal activity recorded on a standard microelectrode track to the subthalamic nucleus (STN) for the determination of the transition between the thalamus and the STN. METHODS: The study is based on analysis of 689 extracelullar single units recorded on 70 tracks passing through the thalamus and the STN. Using four neuron parameters that were correlated with electrode depth, a quality index (QI) for each track was computed and compared with the subjective assessment by the electrophysiologist of the track quality. RESULTS: Subjectively, the transition between the thalamus and the STN was detected in 49 tracks (usual track) and not detected on 21 tracks (unusual tracks). Objectively, spike frequency, cell burst index (BI), signal relative root mean square (RMS) and spike relative amplitude were correlated with electrode depth and used to compute track QI. The average QI index of usual and unusual tracks was 0.25 +/- 0.9 and 0.85 +/- 0.15 (mean +/- confidence interval at P < 0.001), respectively. In 20 patients, QI correlates with post-operative measurement of electrode length in the STN. CONCLUSION: These results demonstrate that simple statistical analysis taking into account the variation of single-unit characteristics with electrode depth can discriminate between useful and useless tracks for the determination of the STN localisation.     

Sparing of perceptual implicit memory despite suppression of the electrophysiological word repetition effect: a study with general anesthetic isoflurane.

OBJECTIVE: Much effort has been devoted to the search for the neurophysiological correlates of implicit memory. A commonly held view is that the early portion (250-500 ms) of the event-related potential (ERP) word repetition effect reflects processes important for perceptual implicit memory whereas the latter portion reflects processes implicated in explicit memory. It is, however, difficult to disentangle with certainty the relative contributions of each form of memory on ERPs since both forms co-exist in normal subjects. To dissociate ERP effect related to implicit and explicit memory, we used isoflurane sedation in normal subjects to suppress explicit remembering while sparing implicit memory. These ERPs were compared with those of non-medicated control subjects. METHODS: Thirteen subjects performed an incidental encoding task for words presented auditorily during the inhalation of a subanesthetic dose of isoflurane. After termination of isoflurane administration, we assessed free recall and recorded ERPs during a syllable completion task (implicit memory) and during a passive listening task (ERP repetition effect). Eleven non-medicated control subjects were tested in a similar manner. RESULTS: The controls showed robust early and late ERP repetition effect. The isoflurane group had implicit memory without free recall and showed no ERP repetition effect. CONCLUSIONS: These findings failed to show an association between any part of the repetition effect and perceptual implicit memory. The results are consistent with the view that processes linked to explicit memory contribute to the ERP repetition effect since there was a marked difference in free recall between the control and isoflurane groups. SIGNIFICANCE: The present study shows that the reversible alterations of memory by general anesthetics can be used to study the neurophysiological correlates of memory processes.     

吡唑烷酮类化合物的抗惊厥作用

对3类14种吡唑烷酮类化合物的抗惊厥作用进行了比较研究,它们对最大电休克惊厥均有对抗作用,作用出现快,但维持时间较短,其中II-f作用最强,对听源性发作和家兔海马注射硫酸锌形成的慢性癫痫模型也有效。此外,III-类尚能对抗戊四唑引起的阵挛性惊厥。     

选择性κ阿片激动剂K-Ⅱ与U-50488的药理作用比较

K-Ⅱ系k阿片激动剂U-50488的同类物。通过部分离体和整体实验比较了K-Ⅱ与U-50488的药理作用。实验发现,K-Ⅱ抑制电刺激兔输精管收缩的IC₅₀值为0.42 nmol/L,U-50488为26.5 nmol/L;K-Ⅱ抑制小鼠运动功能(横筛法)的ED₅₀值为1.7 mg/g,U-50488为15.3 mg/kg;K-Ⅱ的小鼠LD₅₀值为152.5 mg/kg,U-50488为118.4 mg/g;K-Ⅱ明显降低小鼠自发活动的作用比U-50488强5倍。结果表明,K-Ⅱ是一个药理作用较U-50488强的k受体激动剂。     

Low-grade pure and mixed cerebral astrocytomas treated in the CT scan era

Summary From 1974 to 1992, 63 patients diagnosed with low-grade pure or mixed oligo-astrocytoma were seen and treated at our institution. All patients underwent CT scan pre-operatively. There were 20 female and 43 males ranging in age from 12 to 73 years (median age of 33 years). 15 patients had a stereotactic biopsy as the only surgical procedure. 34 had a partial tumor resection and 14 a gross total tumor resection.43 patients were treated with post-operative radiotherapy whereas 20 patients underwent surgery only as part of the initial management. 50 to 60 Gy (median 59.4 Gy) were given with daily fractions of 1.8 to 2 Gy. Tumor volume ranged from 3.4 to 441 cm³. Median tumor volume was larger for radiotherapy treated patients.Median follow-up was 54 months (range of 4 to 240 months). The overall 10 and 15 actuarial survival rates were 37% and 25% respectively. The 5 year survival rate for patients treated at initial diagnosis with surgery alone was 66% and it was 67.3% for patients treated with radiation therapy (P = NS). Prognostic factors having independant significant impact on survival were: extent of surgery, age, gender and tumor volume.As well, survival for patients with low-grade astrocytoma in the CT scan era appears to be improved compared to historical controls in the literature.     

Relationship between severity of lumbar disc disease and disability scores in sciatica patients

OBJECTIVE: To study the association between the clinical examination and the radiological assessment of lumbar disc disease in patients with sciatica. METHODS: The study included 394 consecutive sciatica patients. The patients' disabilities were evaluated by a visual analog pain scale, the Prolo functional-economic rating scale, the modified Roland-Morris disability questionnaire, and the health-related quality of life short form (SF-36) questionnaire. Radiological imaging findings were independently classified according to the Modic criteria into five groups of increasing severity of disc disease. Stepwise multivariate logistic regression was used to determine which scores were significant independent predictors of a severe disc disease (extrusion or sequestration). RESULTS: Of these patients, 9.6% had no disc disease, 3.3% had a bulging, 11.4% had a protrusion, 68.5% had an extrusion, and 7.1% had a disc sequestration. Statistically significant positive linear associations with the severity of disc disease were found for the leg pain scale, the Roland-Morris and Prolo disability scales, and the SF-36 scores related to physical functioning, physical role, and bodily pain (all P < 0.005). A poor (<5) Prolo score (odds ratio, 2.91; 95% confidence interval, 1.74-4.87), a higher leg pain score (odds ratio, 1.16 per centimeter increase; 95% confidence interval, 1.07-1.27), and a lower low back pain score (odds ratio, 0.90 per centimeter decrease; 95% confidence interval, 0.82-0.98) were retained in the multivariate logistic model as independent predictors of severe disc disease. CONCLUSION: The positive correlation between disability status and imaging findings validates both assessment methods. Routine use of disability scores brings a useful contribution to the assessment of sciatica patients.