Hepatic stellate cell activation in liver transplant patients with hepatitis C recurrence and in non-transplanted patients with chronic hepatitis C.

The pathogenic mechanisms of accelerated graft fibrosis in hepatitis C recurrence after liver transplantation (LT) are not well established. The aim of the study was to assess whether a greater activation of hepatic stellate cells (HSC), the major collagen-producing cells in the liver, can occur in these patients as compared to non-LT patients with chronic hepatitis C. We determined the amount of activated HSC by computer-based morphometric analysis of alpha-smooth muscle actin (alphaSMA)-positive cells and the hepatic TGFbeta(1) expression by immunohistochemistry in 46 LT patients with hepatitis C recurrence, 35 non-LT patients with chronic hepatitis C, and 16 controls. Hepatic alphaSMA and TGFbeta(1) expression was higher in LT patients with hepatitis C recurrence than in controls and was correlated with fibrosis stage and progression rate. No significant difference in alphaSMA and TGFbeta(1) expression was observed between LT and non-LT patients with hepatitis C, with the exception of a higher transforming growth factor beta-1 (TGFbeta(1)) expression in non-LT patients in the early stages of fibrosis. LT patients receiving cyclosporine (CsA) or tacrolimus (FK) had a similar fibrosis progression rate and alphaSMA and TGFbeta(1) expression. In conclusion, the accelerated fibrosis observed in LT patients with hepatitis C recurrence does not seem to be related to a greater amount of activated HSC and TGFbeta(1) expression in the grafts of these patients as compared to non-LT patients with chronic hepatitis C. In LT patients, the amount of activated HSC and TGFbeta(1) expression correlated with fibrosis stage and progression, without any apparent influence of the type of calcineurin inhibitor administered.     

P-fimbriae vaccines

To test for cross-protective capacity of two different P-fimbriae vaccines we vaccinated baboons with fimbriae purified from either Escherichia coli strain ER2 or strain JR1. The vaccinated animals showed elevated antibody titers to P-fimbriae from each of the E. coli strains used, suggesting cross-reactivity as was expected from the results of immunoprecipitation of the fimbriae. Enzyme-linked immunosorbent assay inhibition by heterologous P-fimbriae proved this to be true immunologic cross-reactivity.     

Solitary plasmacytoma of bone: clinical features, treatment and survival.

Eleven patients with solitary plasmacytoma of bone were seen between 1978 and 1991. A retrospective review of the clinical features, treatment and survival of these patients was made with the aim of helping to define those at risk for early development of myeloma. Nine patients (82 per cent) had paraparoteinemia at diagnosis. Treatment consisted of local irradiation plus or minus surgery (nine patients) and surgery alone (two patients). No patient received adjuvant chemotherapy. One patient had evidence of both generalized osteopenia and immunoparesis, and progressed to myeloma within six months. Four patients (36 per cent) progressed to myeloma. All of these had paraprotein levels which continued to rise following initial treatment. Three patients died of myeloma at 12, 81 and 144 months and the other patient is alive with myeloma at 76 months. Patients without paraproteinemia at presentation or whose paraprotein decreased after treatment did not progress to myeloma. Three patients have been followed for 8, 11 and 19 years with no evidence of myeloma. Failure of paraprotein to clear after local treatment suggests occult disseminated disease and is predictive of later development of overt myeloma.     

Determining the Alveolar Component of Nitric Oxide in Exhaled Air: Procedures and Reference Values for Healthy Persons

Nitric oxide (NO) production has been described using a 2-compartment model for the synthesis and movement of NO in both the alveoli and the airways. The alveolar concentration of NO (Ca_NO), an indirect marker of the inflammatory state of the distal portions of the lung, can be deduced through exhalation at multiple flow rates. Our objective was to determine reference values for Ca_NO. The fraction of exhaled NO (Fe_NO) was measured in 33 healthy individuals at a rate of 50 mL/s; the subjects then exhaled at 10, 30, 100, and 200 mL/s to calculate Ca_NO. A chemiluminescence analyzer (NIOX Aerocrine) was used to perform the measurements. The mean (SD) Fe_NO was 15 (6) ppb. The mean Ca_NO was 3.04 (1.30) ppb. These values of Ca_NO measured in healthy individuals will allow us to analyze alveolar inflammatory behavior in respiratory and systemic processes.     

Follow up of growth and steroids in premature adrenarche

In a follow up study of 34 patients with premature adrenarche we examined serum adrenal androgen levels and growth. The majority (28/34) showed an upward bend in the growth curve which, at the mean age of 2.3 years, preceded other signs of adrenarche on average by 3.8 years. Pubertal growth spurt was missing or reduced in 50% of the patients (8/16), however, final height did not differ from that expected from parental heights. Adrenal androgens did not remain elevated at adolescence. The mean age at menarche for all the girls was 0.5 years younger than in the general population.Conclusion Our findings imply that premature adrenarche may start earlier than previously recognized. Compared to ordinary growth these children seen to use a greater part of their potential for adult height already at that early age.     

Abuse liability of flunitrazepam among methadone-maintained patients

Abuse liability and acute subjective and psychomotor effects of flunitrazepam were assessed in ten methadone-maintained males with history of benzodiazepine and alcohol use, who voluntarily participated in a double-blind, controlled, cross-over, randomized clinical trial. There were six experimental sessions in which a single oral dose of flunitrazepam 1, 2, and 4 mg; triazolam 0.5 and 0.75 mg; and placebo was given. Evaluations included physiological measures; psychomotor performance tasks (simple reaction time, Digit Symbol Substitution Test, balance task, Maddox-wing device); and self-administered subjective effects questionnaires [Addiction Research Center Inventory (ARCI), Profile of Mood States (POMS), a series of visual analog scales (VAS)]. All drugs but flunitrazepam 1 mg caused an impairment of psychomotor tasks. Effects were more evident with the highest doses of both drugs. Only flunitrazepam 4 mg produced a significant decrease in balance time. Triazolam 0.75 mg induced increases in sedation measured by ARCI-PCAG, depression in POMS, and VAS-drowsiness scores. Flunitrazepam 4 mg caused euphoria-related effects as measured by increases in ARCI-MBG and “high” scores in the VAS. Our findings of flunitrazepam-induced euphoria in methadone-maintained subjects together with epidemiological evidence of flunitrazepam abuse by opioid dependents, suggest that it may be included in the group of benzodiazepines with a relatively high abuse potential. Received: 13 February 1998/Final version: 1 May 1998     

Surveillance for stage I non-seminomatous germ cell tumours of the testis: the optimal protocol has not yet been defined

Forty-six patients with clinical stage I testicular non-seminomatous germ cell tumours were followed up according to a protocol of active surveillance between 1979 and 1987. The median follow-up time was 40+ months. Thirteen patients (28%) relapsed, predominantly in retroperitoneum and/or lung. Ten of these relapses (76%) occurred within 8 months of orchiectomy. Relapses occurred in 7/35 T1 tumours and 5/10 T2 to T4 tumours. No correlation was detected between the histological type and relapse rate. Three late relapses were diagnosed at 23, 29 and 36 months. Eleven of the relapsed patients remain in prolonged complete remission after PVB chemotherapy +/- surgery; one patient, who initially refused treatment at the time of relapse, has died. Another relapsed with predominant elements of rhabdomyosarcoma intermingled with malignant teratoma in a bone metastasis. He had a partial response to PVB chemotherapy but subsequently died. Thirty-four patients (74%) did not undergo lymphography (LG) and had a higher relapse rate (11/34) than those who had LG (2/12); this was not a statistically significant difference in this small series. The policy of active surveillance is not yet the "state of the art" and should be under constant scrutiny with respect to safety and practice.