Recent progress and new trends in the treatment of hepatitis B

The annual rate of progression to cirrhosis in patients with chronic HBV is 0.4 to 14.2% and that of death 4 to 10%. HCC risk increases in parallel with the severity and duration of infection, with an annual incidence less than 0.5% in carriers and 6% in patients with cirrhosis. The main aim of antiviral therapy for chronic "wild-type" HBV infection is to suppress viral replication before cirrhosis and HCC develop. Two drugs are approved: IFN alpha and lamivudine. IFN alpha is costly, has a narrow range of efficacy, safety, and tolerability. Lamivudine is active, cheaper, and better tolerated but has limited efficacy, being associated with increasing resistance and loss of clinical response in the long term. IFN may be the first choice treatment in HBeAg-positive patients with a favourable profile and compensated liver disease. Patients with HBeAg-negative active disease can benefit from 12-24 months IFN treatment if early response is observed. Lamivudine should be started only after considering the uncertainties about duration of therapy and risks of stopping it. In patients with slowly progressive liver disease, treatment is better postponed until effective combination regimens are available. Lamivudine is of paramount importance in end-stage chronic liver disease to suppress HBV replication and allow successful transplantation. The role of interferon in preventing HCC is controversial. In two studies comparing the incidence of HCC in patients with HBeAg-negative chronic hepatitis treated with IFN, HCC developed less frequently in sustained responders than in non-responders in Greece (2 vs. 10%, P = 0.045), but not in Milan (7 vs. 10%, P = ns).     

"Apple-peel" intestinal atresia,ocular anomalies,and microcephaly syndrome: brain magnetic resonance imaging study

We report on a male child with "apple-peel" atresia associated with microcephaly and ocular anomalies. To date, no magnetic resonance imagings have been published. We report on the fourth reported case with this phenotype, but the first to be studied by brain magnetic resonance imaging.     

Circadian pattern of emergency calls: implications for ED organization

A circadian variation has been shown in the onset of acute medical diseases and we postulate that there is a circadian variation in emergency calls. We reviewed the 20,858 emergency calls addressed to the Emergency Coordinating Unit of the Hospital of Ferrara, Italy, from January 1 to December 31, 1998. Precise determination of the time of calls was available from the recordings. Total calls and subgroups by different diseases were categorized into 24 one-hour increments and analyzed for circadian rhythmicity by applying a partial Fourier series. A circadian variation was found for all subgroups, except for alcoholic intoxication. There was a peak frequency of calls in the morning hours for cardiologic, respiratory, and neurologic disease. There was a peak frequency of calls in the afternoon for trauma, neoplastic diseases, and acute poisoning. Organization of quantity and quality of Emergency Department (ED) staff should take into account the increased demand of specific facilities during certain hours of the day.     

Pruritus: a useful sign for predicting the haemodynamic changes that occur following administration of vancomycin

Introduction  

The aim of this study was to investigate the haemodynamic changes that follow the appearance of pruritus during vancomycin administration.     

A noninvasive measure of baroreflex sensitivity without blood pressure measurement

Background Baroreflex sensitivity (BRS) and heart rate variability (HRV) are attenuated in cardiovascular disease and can give important prognostic information. Conventional measures of BRS require expensive or invasive equipment for the beat-to-beat measure of blood pressure (BP). We examined the possibility of developing a simple protocol that would provide a relatively standardized BP stimulus, which might obviate the need to measure BP beat-by-beat. Methods and Results Fifty-five patients with chronic heart failure (mean age 59 [SD 11] years) and 20 healthy control subjects (mean age 53 [SD 14] years, P not significant) underwent 5-minute recordings of BP (by photoplethysmograph) and R-R interval during 0.1-Hz controlled breathing. The size of the oscillations in BP was the same in the 2 groups (3.6 mm Hg vs 4.1 mm Hg, P = .5). There was, however, a significant difference in the amplitude of the R-R interval oscillations (77 ms vs 31 ms, P < .0001). The amplitude of the R-R interval oscillations correlated strongly with BRS (r = 0.81, P < .0001 with controlled breathing BRS, and r = 0.51, P < .0001 with α index). There was no correlation with the size of BP oscillations (r = −0.13, P not significant with controlled breathing BRS, and r = −0.15, P not significant with α index). In a separate study, a group of 22 young patients (mean age 36 years) with type I diabetes mellitus and 28 healthy control subjects (mean age 39 years) underwent measurement of resting HRV and amplitude of R-R interval oscillations during 0.1-Hz breathing. There was no significant difference in triangular index or low-frequency R-R interval power between the 2 groups. There was, however, a significant difference in the amplitude of R-R interval oscillations during controlled breathing between patients with diabetes and healthy control subjects. Total and high-frequency RR interval variability was also significantly different between the 2 groups. Conclusion During 0.1-Hz breathing, the marked difference in BRS between patients with CHF and age-matched control subjects is the result of smaller R-R interval oscillations. In young patients with diabetes, these R-R interval oscillations are significantly smaller than age-matched control subjects, even when some measures of spontaneous HRV are not different between groups. Breathing at 0.1 Hz provides a standard BP stimulus and concentrates spectral power of heart rate at one frequency, enabling simple evaluation of BRS even when BP measurement is not available. (Am Heart J 2002;143:441-7.)     

Expansion of cytotoxic effectors with lytic activity against autologous blasts from acute myeloid leukaemia patients in complete haematological remission

New therapeutic approaches are needed to improve the cure rates in acute myeloid leukaemia (AML). The present study was designed to investigate whether: (1) cytotoxic lymphocytes could be expanded from AML patients in complete remission; (2) their signal transduction machinery was preserved; (3) these cells were capable of producing cytokines involved in the cytolytic process; and (4) these cells showed cytotoxic activity against allogeneic and autologous blasts. By co-culturing blood mononuclear cells with feeder cells, we obtained an average 5.3-fold increase in the total cell number and a 35-fold increase in natural killer (NK) cells. Expression of the zeta chain and of tyrosine kinases of the Src and Syk-ZAP families involved in the triggering of NK functions was analysed on expanded cells. The results demonstrated a signal transduction apparatus preserved and quantitatively similar to that of normal donors. After phorbol myristate acetate and ionomicin stimulation, the ability of expanded cells to produce interferon gamma and tumour necrosis factor alpha was documented. Patients' expanded cells showed a cytotoxic activity against target lines and allogeneic blasts which was similar to that of normal donors. Purification experiments indicated that the NK cell fraction was responsible for most of the lytic effect. More significantly, these cells also exerted a lytic effect against autologous blasts that could be further enhanced following incubation with low-dose interleukin 2. These findings document the possibility of expanding cytotoxic effectors with preserved signal transduction machinery and autologous killing capacity from AML patients in remission, and suggest a new potential immunotherapeutic strategy for the management of early disease recurrence or of residual disease.     

Diabetes insipidus as first manifestation of acute myeloid leukaemia with EVI‐1‐positive, 3q21q26 syndrome and T cell‐line antigen expression: what is the EVI‐1 gene role?

Two cases of acute myeloid leukaemia (AML) with CD2 and CD7 expression associated with diabetes insipidus (DI) as the initial symptom are presented. Both patients had t(3;3)(q21;q26) associated with monosomy 7 and EVI-1 overexpression. No neurohypophysis infiltration was evident. One patient died during induction chemotherapy, the other did not respond to therapy and died with persistent DI. Our findings further support the existence of a distinct AML entity characterized by the presence of DI, abnormalities of chromosome 3q, dysmegakaryopoiesis and poor outcome, and provide evidence of EVI-1 gene involvement. The possible role of chromosome 3q26 abnormalities in determining this peculiar clinical-biological association is emphasized.