Interleukin-12 induces relapse in experimental allergic encephalomyelitis in the Lewis rat

Acute, monophasic experimental allergic encephalomyelitis (EAE) in the Lewis rat shows pathological similarities to the human disease multiple sclerosis (MS). Rats that recover from EAE are essentially resistant to disease reinduction, unlike MS in which relapses are frequently associated with common bacterial and viral infections. As macrophage-derived interleukin (IL)-12 is a critical component of innate resistance to bacterial infection and appears to directly activate encephalitogenic T cells in vivo, the ability of this cytokine to reinduce paralysis in EAE was examined. Paralytic disease was exacerbated by intraperitoneal IL-12 administration and could be reinduced up to 1 week after recovery from the primary clinical episode. Concomitant with worsening of initial clinical signs and relapse was an increase in the ratio of macrophages to T cells in brain stem perivascular cuffs and the expression of inducible nitric oxide synthase in cells with both macrophage and microglial morphology. These findings suggest that IL-12 may contribute to macrophage-mediated disease exacerbation and relapse in patients with MS.     

Should patients with sleep apnoea/hypopnoea syndrome be diagnosed and managed on the basis of home sleep studies?

The purpose of this study was to analyse the validity and the economic efficiency of a portable monitor of respiratory parameters (PMRP), used in a home setting for the diagnosis of sleep apnoea/hypopnoea syndrome (SAHS). Eighty nine patients with suspected SAHS were studied in two settings: in the sleep laboratory using full-polysomnography (full-PSG); and at the patient's home using a PMRP. In the home setting, 50 patients were assisted by a technician and 39 set up the equipment themselves. SAHS (apnoea/hypopnoea index (AHI) >10 events x h(-1) by means of full-PSG) was diagnosed in 75 of the 89 patients. An acceptable agreement was obtained between the AHI measured by full-PSG and PMRP, according to the Bland and Altman method of concordance (mean bias 2.56; 95% confidence interval 3.25). Sensitivity and specificity of PMRP were adequate for diagnostic purposes; however, their values rely on the prior PMRP-AHI cut-off point selected with reference to full-PSG-AHI >10. The clinical therapeutic decision taken after PMRP agreed with that taken with full-PSG in 79 patients (89%). Although 10% of the studies with an individual set-up needed repetition, both of the domiciliary modalities (with and without a technician's intervention) were, economically, about three times more efficient than full-PSG. In conclusion, we believe that patients with a suspected sleep apnoea/hypopnoea syndrome should initially be studied in a home setting with a portable monitor of respiratory parameters, since it is a reliable method with an acceptable cost-effective profile.     

The effect of oxygen free radicals on calcium current and dihydropyridine binding sites in guinea-pig ventricular myocytes

1. We used electrophysiological and binding techniques to determine the effects of oxygen free radicals (OFRs) generated by dihydroxyfumaric acid (DHF, 5 mM) on calcium current and dihydropyridine binding sites in guinea-pig isolated ventricular myocytes. 2. Binding of [3H]-PN200-110 to isolated ventricular myocytes revealed one population of binding sites with a KD of 0.11 +/- 0.01 nM and Bmax of 139.1 +/- 6.9 fmol mg-1 protein (n = 24). After 15 min of exposure to DHF, the density, but not the affinity of [3H]-PN200-110 binding sites was significantly (P < 0.01) reduced to 35% of the control value (Bmax = 49.4 +/- 3.7 fmol mg-1 protein, KD = 0.11 +/- 0.01 nM, n = 15). In the presence of superoxide dismutase (SOD) and catalase (CAT) the reduction in [3H]-PN200-110 binding sites was almost completely prevented (Bmax = 120.5 +/- 7.4 in control, n = 4 and 98.8 +/- 7.4 fmol mg-1 protein in DHF plus SOD and CAT, n = 4). KD values were not modified (0.08 +/- 0.01 in control and 0.09 +/- 0.01 nM in DHF plus SOD and CAT). 3. The time-course of the reduction of [3H]-PN200-110 binding sites by OFRs was paralleled by the decrease in L-type calcium current (Ica,L) measured in patch-clamped guinea-pig ventricular myocytes either in the absence or in the presence of EGTA in the patch pipette. In the former conditions OFRs induced the appearance of calcium-dependent alterations, i.e. the transient inward current, within 10 min. After 30 min of incubation with DHF, [3H]-PN200-110 binding sites were reduced to 25% of the control value. 4. In myocytes incubated with the antilipoperoxidant agent, butylated hydroxytoluene (BHT, 50 microM), the decrease in [3H]-PN200-110 binding sites caused by DHF was partially prevented (Bmax values after 30 min exposure to DHF were 55.5 +/- 1.9 and 23.7 +/- 5.9 fmol mg-1 protein in the presence and in the absence of BHT respectively, P < 0.05). BHT did not affect the decrease in [3H]-PN200-110 binding sites during the first 15 min of exposure to DHF, but was able to prevent completely the further decrease occurring during the following 15 min of incubation with OFRs. 5. Our results demonstrate that the OFR-induced decrease in calcium current is associated with a reduction in DHP binding sites. The decrease in calcium current and in calcium channels may be implicated in the mechanical dysfunction associated with oxidative stress.     

Zoonotic Brugian lymphadenitis. An unusual case with florid monocytoid B-cell proliferation

Human infection with a zoonotic Brugia species in the United States is uncommon. Positive identification of the filarial nematode is required for histopathologic diagnosis. Many cases may go unrecognized because of the nonspecific clinical manifestations and the nondiagnostic histologic changes occurring in involved lymph nodes. A case of zoonotic Brugia lymphadenitis is described in a patient from Rhode Island, in which a small nongravid female worm was identified in a lymph node biopsy specimen. The lymph node also showed a spectrum of reaction changes including the presence of florid monocytoid B-cell proliferation, which has not been described in association with zoonotic Brugian filariasis.     

Management of lymphoproliferative disorders after cardiac transplantation

We conducted a retrospective study of 516 cardiac recipients who underwent transplantation between April 1983 and April 1992, 19 of whom had development of post-transplantation lymphoproliferative disorders (PTLDs). These 19 patients presented with involvement of lung (5), gastrointestinal tract (5), disseminated disease (6), and adenoids and lymph nodes (3). B-cell proliferations ranging from an atypical hyperplasia to malignant lymphoma developed in 18 patients, and mixed cellularity Hodgkin's disease developed in 1 patient. The 19 patients with PTLD displayed a predominance of both women and cardiomyopathy as the indication for transplantation when compared with two separate control populations. No correlation was found between demographic criteria analyzed and (1) early versus late diagnosis of PTLD after transplantation, (2) the site of PTLD involvement, or (3) the histopathologic category of the PTLD lesion. Patients with gastrointestinal tract and lung PTLD involvement enjoyed an improved survival after both transplantation and PTLD diagnosis when compared with patients with PTLD involvement of all other extranodal sites. We report a high incidence of PTLD involving the lung and gastrointestinal tract in our cohort study. These sites of involvement responded better to a reduction in immunosuppression than did the other extranodal sites of involvement.     

Prevalence of serologic markers of HBV, HDV, HCV and HIV in non-injection drug users compared to injection drug users in Gran Canaria, Spain

Von Hippel-Lindau disease (VHL) is an autosomal dominant tumour syndrome caused by germline mutations of the VHL tumour suppressor gene located on chromosome 3p25-26. In VHL tumours may occur in 14 different target organs, including the eye. Retinal angiomas are considered the first manifestation of VHL disease in 43% of cases, and the cumulative probability of developing a retinal angioma in one or both eyes rises during each decade of life, reaching 80% for patients over 80 years old. Since 1976 patients with VHL at the University Hospital of Utrecht and their at-risk relatives have been screened periodically by a multidisciplinary team. Long-term follow-up ophthalmological data were analysed with special attention to natural course and results of treatment. In addition, we looked for a genotype-phenotype correlation. Retinal angiomas were found in all families. In one large family with a missense mutation (V170D) of the VHL gene, in which the complete spectrum of visceral- and central nervous system (CNS) features of VHL is present, macular, parapapillary, optic disc and ora serrata angiomas were also found. In general, however, a clear-cut genotype-phenotype correlation could not be found. Only early detection and treatment of peripheral retinal angiomas can be expected to decrease the percentage of patients with decreased visual acuity. Therefore, early detection and treatment of these tumours is of paramount importance. Ophthalmological screening of patients and persons at risk should start as early as possible. In patients with apparently sporadic retinal angiomas it is advisable to perform germline DNA analysis, since the risk of developing VHL is high, especially if the angiomas are bilateral, or unilateral and multifocal, if the patient is young, or if there is a family history suggestive of VHL.     

alpha B-crystallin and hsp25 in neonatal cardiac cells--differences in cellular localization under stress conditions

OBJECTIVES: The aim of this study was to determine (a) whether delay in femur fracture stabilization beyond twenty-four hours in patients with head injury increased the risk of pulmonary complications and (b) whether immediate (up to twenty-four hours) femur fracture stabilization increased the risk of central nervous system (CNS) complications. DESIGN: Retrospective analysis. MATERIALS AND METHODS: Thirty-two patients with femur fracture and head injury were identified. Fourteen underwent immediate stabilization of their fractures, and eighteen underwent delayed (four-teen patients) or no (four patients) stabilization of their fractures. RESULTS: In the immediate stabilization group, five patients had severe head injuries [Glasgow Coma Score (GCS) < or = 8] and nine had mild head injuries (GCS > 8). In the mild head injury group, no patient had a pulmonary complication and one had a CNS complication. In the severely head-injured group, one patient had a pulmonary complication and no patient had a CNS complication. In the delayed stabilization group, six patients had mild head injuries (GCS > 8) and twelve had severe head injuries (GCS < or = 8). In the mildly head injured group, one patient had a pulmonary complication, two patients had CNS complications, and one patient died. In the severely head injured group, nine patients had pulmonary complications, three patients had CNS complications, and one patient died. Logistic regression identified delay in femur stabilization as the strongest predictor of pulmonary complication (p = 0.0042), followed by severity of chest Abbreviated Injury Score (AIS; p = 0.0057) and head AIS (p = 0.0133). Delaying fracture stabilization made pulmonary complications forty-five times more likely. Each point increase in the chest AIS and head/neck AIS increased the risk of pulmonary complication by 300 percent and 500 percent, respectively. A statistically significant predictor of CNS complications could not be identified by using logistic regression. CONCLUSION: Delay in stabilization of femur fracture in head-injured patients appears to increase the risk of pulmonary complications. However, due to selection bias in this patient sample, this question cannot be definitively answered. Early fracture stabilization did not increase the prevalence of CNS complications.