Docetaxel neuropathy: a distal axonopathy

Docetaxel has been implicated as a causative agent in peripheral neuropathy, but pathological changes in peripheral nerve have not been described. During docetaxel treatment a 54-year-old man developed a sensorimotor polyneuropathy when the overall docetaxel dosage was 540 mg/m². Neurophysiological investigation revealed a sensorimotor axonal neuropathy. Fascicular sural nerve biopsy showed an axonal neuropathy with a preferentially loss of large myelinated fibers. There was evidence of considerable fiber regeneration. Sensory and motor symptoms progressively improved after docetaxel withdrawal. Received: 21 January 1999 / Revised, accepted: 25 March 1999     

Heparin/heparan sulfate anticoagulant glycosaminoglycans in human plasma of healthy donors: preliminary study on a small group of recruits

Glycosaminoglycans in normal human plasma, mainly represented by chondroitin sulfates and heparan sulfates/heparin (HSGAGs), show a specific distribution in the Cohn-Oncley fractions of human plasma. In the present study we investigated their effects on coagulation. Plasma was fractionated following the procedure of Cohn-Oncley, and each fraction was treated for extraction of glycosaminoglycans after extensive proteolysis; the anticoagulant activity in the extracted samples was measured by activated partial thromboplastin time (APTT). The effects of the samples containing HSGAGs on factor II and factor X activities, before and after treatment with heparinase I, were also measured. The molecular weight of HSGAGs was determined by polyacrylamide gel-electrophoresis. Cryoprecipitate and fraction I, fraction II+III, and fraction IV-1 (the fractions containing HSGAGs) prolonged the APTT, whereas fractions IV-4 and V had no effect on the APTT. Fractions containing HSGAGs showed effects on factor II and factor X activities that were sensitive to heparinase I treatment. The molecular weight of HSGAGs recovered in cryoprecipitate and fraction I was 15-18 kDa; that of HSGAGs recovered in fraction IV-1 was 12.0 kDa. In conclusion, these results demonstrate that HSGAGs of different molecular weight, endowed with anticoagulant activity, circulate in normal human plasma in association with specific proteins involved in the regulation of hemostasis; and that endogenous HSGAGs play a role in maintaining the antithrombotic/hemostatic balance in normal human plasma.     

Use of a novel phosphatase test for simplified identification of species of the tribe Proteeae.

Phosphatase activity of 334 isolates of the tribe Proteeae carefully identified to species level has been evaluated by using both a number of conventional tests and three versions of the novel methyl green-phenolphthalein (MGP) method (G. Satta. R. Pompei, G. Grazi, and G. Cornaglia, J. Clin. Microbiol. 26:2637-2641, 1988). We found that the different species of Proteeae show different and easily distinguishable. behaviors by the MGP method, while all of them behave in a uniform way in the conventional tests. On studying the mechanism underlying these different behaviors, we found that the phosphatase activity of Morganella morganii and Providencia stuartii is higher than that of all other members of the family Enterobacteriaceae. Furthermore, we found that all P. stuartii strains display the property (shared by virtually none of the other species of Enterobacteriaceae) of excreting significant amounts of phosphatase. This extracellular activity is reliably detected by the MGP method but not by conventional tests. Finally, by exploiting the peculiar phosphatase activity of this tribe, as revealed by the MGP method, we devised a simple scheme for routine identification of the species of Proteeae and evaluated its reliability by comparing it with three commonly used commercial kits. The new scheme proved much simpler, but also more reliable, since identifications obtained by this method were in almost complete accord (99%) with those of the reference identification schemes, while in the commercial systems examined the percentage of errors ranged from 13 to 14 in the identification of Providencia species.     

Percutaneous intralesional brushing of cystic lesions of bone: a technical improvement of diagnostic cytology

A modified bronchial brush is presented as a new cytologic method to improve the value of fineneedle aspiration biopsy in the diagnosis of cystic lesions of bone. Four female and six male patients ranging in age from 10 to 44 years were studied. In all cases intralesional brushing was percutaneously performed under fluoroscopic control with local anesthesia. Fine-needle aspiration biopsy preceded intralesional brushing and was performed as described elsewhere. The brush was driven into the walls and septa of an osteolytic lesion through a 14-G needle; material obtained was fixed and processed for cytological and/or histological examinations.     

Effects of Short-Term Risedronate on Bone Resorption and Patient Satisfaction in Postmenopausal Osteoporosis Patients

This multicenter, open-label study evaluated the effects of short-term risedronate on bone resorption and patient satisfaction in postmenopausal women with osteoporosis in Brazil. Entry requirements included: osteoporosis of the spine/femoral neck diagnosed by a bone mineral density (BMD) T-score ≤ ?2.5 or radiographic fragility fracture within the last year and no treatment with osteoporosis medication in the preceding 3 mo. Patients were treated with once weekly risedronate of 35 mg for 12 wk. Patients also received 1000 mg calcium carbonate and 400 IU vitamin D. The main outcome was the effect on bone resorption, as assessed by the quantification of serum C-telopeptide of type I collagen (CTX). Of the 556 women screened, 480 women received ≥1 dose of study drug (intent-to-treat [ITT] population), and 390 completed treatment (81%). After 12 wk, CTX decreased in 94% of patients (from 0.419 ± 0.234 to 0.158 ± 0.171 μg/L, p < 0.0001). Mean CTX reduction was 60.6%. Patient satisfaction was good/excellent in 91.7% of patients. A total of 156 adverse events (AEs) were reported by 113 (23.5%) patients in the ITT population. Digestive symptoms emerged or worsened in 7.1% and 3.5%, respectively. Five patients (1.0%) experienced serious AEs, not considered to be related to risedronate. In conclusion, risedronate significantly reduced serum CTX after 12-wk treatment. Almost all patients reported good/excellent satisfaction.     

Infliximab and the risk of latent viruses reactivation in active Crohn's disease

BACKGROUND: Infliximab is used for refractory Crohn's disease but there are concerns regarding long-term safety. Recently, JC-polyomavirus (JCV) was studied after 3 cases of progressive multifocal leukoencephalopathy (PML) were found after treatment with natalizumab. The aim of this study was to investigate the short-term effect of infliximab on reactivation of several harmful latent viruses. METHODS: Sixty consecutive patients scheduled for infliximab induction course were prospectively enrolled. Blood samples were taken before each infliximab infusion at 0, 2, 6, and 14 weeks. Specific polymerase chain reaction (PCR) analyses were performed to detect JCV, Epstein-Barr virus (EBV), human herpes virus-6, (HHV-6), -7, -8, and cytomegalovirus (CMV). RESULTS: Indications to infliximab were luminal and fistulizing disease in 49 and 15 cases, respectively. Clinical improvement and remission were achieved in 54 (90%) and 39 (65%) of patients, respectively, at 6 weeks. No patient was JCV-positive at any timepoint. EBV serology was positive for 59/60 patients (98%); EBV-PCR tests were transiently positive (>40 copies/10(5) Peripheral blood mononuclear cells, PBMC) in 4 (7%) patients after infliximab, but in each case were negative at subsequent timepoints. All patients were negative for HHV-6, -7, and -8 at all timepoints. CMV serology was positive in 42 patients (70%), but no CMV-PCR-positive patient was observed. There was no association between concomitant treatments or clinical characteristics and viral status. CONCLUSIONS: Our results support the safety of short-term infliximab treatment with respect to latent virus reactivation. The long-term effects of infliximab, particularly for the issue of lymphoproliferative disorders, warrants further studies with larger populations, but so far data are reassuring.     

Association study of the HLA-A2 allele in Italian Alzheimer disease patients

Association of the A2 allele of the human leukocyte antigen (HLA) with Alzheimer disease (AD) is still controversial. The authors evaluated HLA-A2 association with AD in 173 Italian AD patients, considering also the possible interaction with APOE pattern, age of onset and gender. No evidence of any association was found.