T-lymphocyte immunointerferon receptors in patients with multiple sclerosis

Multiple sclerosis (MS) is a T-cell-mediated autoimmune demyelinating disease of the central nervous system (CNS), associated with an altered immunoregulation. Interferon (IFN)-, also known as immune IFN, is a cytokine with several effects on the immune system. Specific IFN- receptors have been found on human lymphocytes, as well as on other cell types (e.g. gliocytes), even in the CNS. The aim of the present study was to evaluate IFN- binding on peripheral blood T-lymphocytes from MS patients, compared with those from healthy subjects. Thirty-two patients were selected according to the classical criteria for definite MS; as controls, 21 healthy subjects were studied. We have found that T-lymphocytes from MS patients bear a significantly smaller amount of IFN- receptors than those from controls [B _max: 568, 18 vs 708, 14 (mean, SE) receptors/cell]. Such IFN- binding sites are of the same type in patients and healthy subjects [K _d: 1.0, 0.05 vs 0.9, 0.02 (mean, SE) nM]. These findings are discussed in terms of immunopathogenesis of MS, since it has been reported that activated T-lymphocytes have decreased amounts of IFN- receptors.     

Growth plate injury of the long bones in treated β-thalassemia

In 12 patients affected by thalassemia major who received an intensive transfusion regimen combined with continuous iron chelation therapy (desferrioxamine 50–80 mg/kg daily), radiologic abnormalities of the long bones were observed similar to those observed in rickets and scurvy. These abnormalities were associated with a growth retardation. The pathogenesis of these lesions is uncertain, but probably the toxic effect of desferrioxamine plays an important role in their development. A relative deficiency of vitamins D and/or C cannot be entirely excluded.     

Intrafamilial phenotype variation in Friedreich's disease: possible exceptions to diagnostic criteria

Summary Three families are described which include members with typical Friedreich's disease (FD) and others who are ataxic but do not satisfy all the diagnostic criteria for that disease. In family A two patients have an early-onset, rapidly progressive FD, while two others have a late-onset, more benign form. In families B and C one member has typical FD, and another has a similar ataxic syndrome, except for preservation of knee jerks. Laboratory evaluation is consistent with the diagnosis of FD in all cases. FD diagnosis appears justified in secondary cases with late onset or preserved tendon reflexes, provided that the index case fulfils all diagnostic criteria. Whether the diagnosis of FD is tenable in sporadic atypical cases remains to be seen. Echocardiographic and neurophysiological examination may be valuable in classifying such cases.     

Lipoplastics of Legs: Our Experience with a New Cannula Compared with Classical Technique

The Authors compare the results obtained between two groups of patients suffering from leg lipodystrophy, who were subjected to a reducing lipoplasty. In the first group, surgeons made use of a new sort of cannula, deprived of the classical grip, whereas in the second group, they employed the traditional probe. The best results, achieved with the first group, prove this new operating system is really effective, particularly on legs, for the following reasons: (1) Higher precision and better control of the instrument (2) Swan-neck cannula abolition (3) Opportunity to operate with both hands (4) Halved operating time (5) No tiredness after the operation.     

Pegylated arginine deiminase treatment of patients with unresectable hepatocellular carcinoma: results from phase I/II studies.

PURPOSE: Recently, we reported that a large number of human hepatocellular cancer (HCC) cell lines were auxotrophic for arginine. Here we report the results obtained with the amino acid-degrading enzyme arginine deiminase (ADI) conjugated to polyethylene glycol (ADI-SS PEG 20,000 mw) as a means of lowering plasma arginine to treat HCC. The study was a cohort dose-escalation phase I/II study. PATIENTS AND METHODS: Pharmacodynamic studies indicated an ADI-SS PEG 20,000 mw dose level of 160 U/m(2) was sufficient to lower plasma arginine from a resting level of approximately 130 micromol/L to below the level of detection (< 2 micromol/L) for more than 7 days, a dose later defined as the optimal biologic dose. All patients were to receive three cycles at the optimum biologic dose. RESULTS: This therapy was well tolerated, even in patients who had no detectable plasma arginine for 3 continuous months of therapy. Of the 19 patients enrolled, two had a complete response, seven had a partial response, seven had stable disease, and three had progressive disease. The median survival for the 19 patients enrolled on this study was 410 days, with four patients still alive at present (> 680 days). CONCLUSION: Elimination of all detectable plasma arginine in patients with HCC was well tolerated and seemed to be effective in the treatment of some patients with HCC. Further testing of ADI-SS PEG 20,000 mw in a larger population of individuals with HCC as well as other human tumors auxotrophic for arginine is warranted.     

Correlation between Epstein Barr virus antibodies, serum IgE and atopic disease

It is currently accepted that vinil infections may influence the development of atopy. In the present study we evaluated serum IgE levels as well as the prevalence of symptom-, indicative of utopic disease and EBV antibodies in 353 children aged from I month to 19 years. Antibodies against EBV were detected by immunofluorescence. IgE levels in serum were measured by en/. yme imimmoassay. Dividing ihe study population according to EBV seropositivity and age, we noted that the prevalence of high IgE levels (> 2 s. d.) was, in total, more frequent in the EBV negative (32. 9%) than in the positive subjects (27. 6%). Interestingly, this higher prevalence was found only in the groups aged under six, especially in the 7 to 29 month group, where it was statistically significant (p=0.037), whereas in the 6-19 year group the situation was reversed. Furthermore, selecting only the atopic children younger than 3 years of age with high IgE levels and clinical symptoms of atopy (wheezing and/or dermatitis) it was possible to demonstrate lower EBV seropositivity compared with the normal IgE controls for each group, even though these differences were not statistically significant. In conclusion, the results of our study suggest that, in our selected population, EBV infection in the first years of life is associated with a lower prevalence of high IgE levels.     

Expression and activity of CYP2E1 in circulating lymphocytes are not altered in diabetic individuals

Cytochrome P4502E1 (CYP2E1) plays an important role in ROS production thus favouring accelerated membrane lipid peroxidation. This isoform is strongly expressed in the liver but it can be also found in lymphocytes. As such, lymphocyte may provide a non-invasive accessible pool for screening CYP2E1 expression in man. We have, therefore, analysed CYP2E1 expression and activity in lymphocyte microsomes from 12 healthy controls, 11 type 1 and 12 type 2 diabetic subjects by using Western blot and enzymatic activities. Immunoblotting did not show difference among CYP2E1 protein bands in controls, type 1 and type 2 diabetics. To assess CYP2E1 activity we used the 7-ethoxy-4-trifluoromethylcoumarin (7-EFC), as a fluorescent substrate. The rate of deethylation of 7-EFC from controls did not differ from type 1 and type 2 diabetic subjects. The lack of any difference in CYP2E1 activity also was confirmed by the NADPH-dependent microsomal lipid peroxidation CCL4-induced assay showing similar peroxidation rates among controls and diabetic subjects. The results show that CYP2E1 expression/activity in lymphocytes is not enhanced in diabetes.     

Management of jugular paragangliomas: the Gruppo Otologico experience.

OBJECTIVE: The objective of this study was to review the outcome of surgical management in patients of jugular paragangliomas. STUDY DESIGN: We conducted a retrospective case review. SETTING: Tertiary care otology and skull base center. MATERIALS AND METHODS: Fifty-five patients with the diagnosis of a jugular paraganglioma (Fisch Class C and D Glomus Jugulare) were managed over a period of 15 years. All patients with adequate follow up and complete records (53 cases) were reviewed with emphasis on the results of surgical management and the factors influencing them. INTERVENTION: All 53 patients were managed with a view to surgically extirpate the tumor. The primary approach was the infratemporal fossa approach-Type A used in the majority of the patients. In eight cases, the procedure was staged owing to the presence of large intracranial extension. Three patients required additional procedures to ameliorate the after-effects of lower cranial nerve resection. RESULTS: Gross total tumor removal was achieved in 49 patients. There were five cases of recurrence. Coupled with the residual tumors in five patients, the surgical control achieved was 83%. There was no perioperative mortality. There were two cases of postoperative cerebrospinal fluid leak, both of which required surgical exploration and closure. The facial nerve was resected in seven patients. The overall preservation rate of clinically uninvolved lower cranial nerves was 75%. CONCLUSIONS: The low level of complications along with a high surgical control achieved makes surgery the primary mode of treatment in the vast majority of these tumors, regardless of the size and location.