RNA editing signature during myeloid leukemia cell differentiation.

Adenosine deaminases acting on RNA (ADARs) are key proteins for hematopoietic stem cell self-renewal and for survival of differentiating progenitor cells. However, their specific role in myeloid cell maturation has been poorly investigated. Here we show that ADAR1 is present at basal level in the primary myeloid leukemia cells obtained from patients at diagnosis as well as in myeloid U-937 and THP1 cell lines and its expression correlates with the editing levels. Upon phorbol-myristate acetate or Vitamin D3/granulocyte macrophage colony-stimulating factor (GM-CSF)-driven differentiation, both ADAR1 and ADAR2 enzymes are upregulated, with a concomitant global increase of A-to-I RNA editing. ADAR1 silencing caused an editing decrease at specific ADAR1 target genes, without, however, interfering with cell differentiation or with ADAR2 activity. Remarkably, ADAR2 is absent in the undifferentiated cell stage, due to its elimination through the ubiquitin-proteasome pathway, being strongly upregulated at the end of the differentiation process. Of note, peripheral blood monocytes display editing events at the selected targets similar to those found in differentiated cell lines. Taken together, the data indicate that ADAR enzymes play important and distinct roles in myeloid cells.

Evaluation of different staging systems for Kaposi's sarcoma in HIV-infected patients.

The records of 49 consecutive AIDS patients with Kaposi's sarcoma were analysed retrospectively to assess the prognostic value of the four staging systems proposed for epidemic Kaposi's sarcoma. The classifications by Krigel and Mitsuyasu do not describe exactly the characteristics of the disease, and do not give enough information on survival. Our study confirms that CD4+ cell depletion, systemic symptoms and opportunistic infections at diagnosis are the major prognostic factors and influence survival to a great extent, as shown by Krown and Chachoua.

Case report: Retinopathy after malaria prophylaxis with chloroquine.

Chloroquine retinopathy (CR) is a major complication of long-term malaria prophylaxis (LTMP) causing permanent visual dysfunction and occasionally blindness. After an extensive review of the published accounts of CR, we concluded that the risk of retinopathy in subjects receiving LTMP is limited to a cumulative dose that does not exceed 140 g. We present a case of CR that occurred after 8 years of malaria prophylaxis with chloroquine at a cumulative dose of 125 g. Because a threshold dose of chloroquine for retinal toxicity has not been established, careful, ongoing screening is required, especially as the cumulative dose increases.

[Hepatitis A and hepatitis B. Clinical, epidemiological and differential immunological elements]. / Epatite A ed epatite B. Elementi clinici, epidemiologici ed immunologici differenziali

The Authors have already related in various papers the results of their research on humoral and cellular immunity in the course of viral hepatitis in relation to the behaviour of HBsAg determined with various methods and recently with the radio-immune assay. Since the high sensitivity of this latter technique consents a sufficiently precise differentiation of hepatitis into HBAg-positive (hepatitis B) and HBAg-negative (hepatitis A), the Authors have intended studying in this work the eventual clinical epidemiological and immunological differences between the two types of hepatitis, analyzing the results of their previous studies, extending the case data and gathering numerous other personal observations, clinical and laboratory, not yet published. The study was limited to 136 patients with viral hepatitis in wwhich the test for HBsAg was effected with RIA: of these 58 were HBAg+ and 78 HBAg-. Initially is discussed the incidence of two types of hepatitis in relation to age and sex and then the comparative incidence between them of the various routes of contagion. Particularly emphasized is the possibility of direct transmission of HBAg+ hepatitis, often responsible for infection within the family. The comparative determination of transaminases, bilirubin, immunoglobulins and complement has revealed some interesting variations in the behaviour of the two types of hepatitis. Instead, cellular immunity, studied by the rosette E technique, appeared depressed in the initial phase of sickness in both types of hepatitis. Space is dedicated to the behaviour of HBsAg in acute HBAg+ hepatitis in relation to the immunoglobulins and complement and in relation to the normalization of the transaminases and bilirubinemia. After a few brief observations on the frequent appearance of a joint symptomatology in the course of viral hepatitis, particularly in the HBAg+ form, the Authors report the data relative the evolution of the hepatitis cases examined. The percentage of a complete cure are about equal between hepatitis A and hepatitis B even recovery is significantly faster in the first type of hepatitis (HBAg-).

A meta-analysis of research on sensory integration treatment.

OBJECTIVE: The purpose of this study was to find whether existing studies of treatment using sensory integration approaches support the efficacy of these approaches. METHOD: With meta-analysis, the results of sensory integration efficacy research studies published from 1972 to the present were synthesized and analyzed. Sixteen studies were used to compare sensory integration effect with no treatment (SI/NT), and 16 were used to compare sensory integration effect with alternative treatments (SI/ALT). Overall average effect sizes, comparisons of the effect sizes for different dependent variables, and secondary factors associated with effect size variation were examined. RESULTS: The weighted average effect size of SI/NT studies was .29. However, there was a significant difference between the average effect sizes of the earlier studies (.60) and the more recent studies (.03). Of the outcome measures, larger effect sizes were found in the psychoeducational category (.39) and motor category (.40). Of SI/ALT studies, the average effect size was .09, not significantly different from zero. CONCLUSION: Three central conclusions can be made. First, in the SI/NT comparison, a significant effect was replicated for sensory integration treatment effects in earlier studies, but more recent studies did not show overall positive effects. Second, larger effect sizes were found in psychoeducational and motor categories. Third, sensory integration treatment methods were found to be as effective as various alternative treatment methods.

Control strategies for tuberculosis and role of public health service.

The best strategy of prevention of tuberculosis is to control the contact with tubercle bacilli, implement the suggested therapeutic protocol and verify the patient's compliance with the therapy. To this purpose, it is important to plan outpatient controls, supply enough drugs to the patient to last until the first outpatient control and include the patient in directly observed therapy (DOT) programs. At the hospital level there should be three possibilities: isolation of potentially contagious patients, application of structural devices and of respiratory protection. The role of the Public Health Service in the control of tuberculosis at present is of the utmost importance to optimize prevention measures as well as to prepare protocols for health care and therapy. Particular controls are necessary in health facilities providing care for HIV-positive subjects where a program of control of tuberculous infection should be implemented according to the guidelines of the Ministry of Health.

[Detection of Australia antigen by radioimmunoassay during a course of viral hepatitis]. / Determinazione dell'antigene Australia con il metodo radioimmunologico in corso di epatite virale

The AA. carried out the research of Australia Antigen by radioimmunoassay (RIA) as well as with counter-electrophoresis technique (CE) on 142 patients with acute viral hepatitis. For comparison the RIA determination of the Australia Antigen was also performed on 26 blood donors, already established Au positive by a preliminary screening with CE method. On the 142 patients examined, the RIA permitted the detection of 19 as Au positive above the number evidenced by the less-sensitive CE technique. The Au antigen levels, determined quantitatively in conventional units (c.u./0,1 ml of serum), continually decreased with the progress of the disease toward recovery. Yet, in 23 cases (44,3%), the antigen was still present in the serum after normalization of transaminases. The AA. call attention to the importance the Au positive hepatitis convalescents and Au positive blood donors could have in the transmission of the disease. The antigen levels of blood donors, when determined with RIA, were found comparable to those observed in the acute phase of viral hepatitis.

[Detection of HBsAg and the related antibody (HBsAb) with the radioimmunological method. Behavior of the HBeAg-HBcAb system in HBsAg-positive patients]. / Ricerca con metodo radioimmunologico dell'HBsAg e del relativo anticorpo (HBsAb). Comportamento del sistema HBeAg-HBeAb nei pazienti HBsAg-positivi.

A radioimmunological assay was made of HBsAg and HBsAb in 183 patients during the course of acute viral hepatitis, 23 with prior HBsAg-positive hepatitis, 72 with chronic liver disease, 822 blood donors, 44 patients and 28 staff members from two dialysis centres, and the medical and paramedical staff of several high-risk departments. Microimmunodiffusion on agar was also used to determine HBeAg and HBeAb in the same 183 acute hepatitis patients, 37 HBsAg+ blood donors, 20 asymptomatic HBsAg carriers, the patients of two haemodialysis centres and the staff of departments at high risk for hepatitis B. Attention is drawn to the marked incidence (5.5%) of chronic HBsAg carriers in the blood donors, and the considerable circulation of virus B in the population examined, HBsAb-positivity (27.6%) being also an expression of this. Stress is also laid on the diagnostic and prognostic significance of the study of the HBsAg-HBsAb system during acute and chronic hepatitis. The importance of serum hepatitis B markers in the transmission of this disease in dialysis centres and other high-risk departments and in its prevention is underscored. Lastly, emphasis is laid on the appreciable progress that analysis of the e-anti-e system offers in the prognostic assessment of type B hepatitis, attention being also drawn to the fact that the dynamics of this system is even more complex and interesting than had first been thought. An assessment of this kind is useful in the differentiation of "contagious" and "non-contagious" HBsAg carriers.

Comparison of two medications in central nervous system toxoplasmosis in patients with AIDS.

We retrospectively examined 39 patients with AIDS and central nervous system toxoplasmosis in order to determine the efficacy and safety of two combinations: pyrimethamine-sulfadiazine and pyrimethamine-clindamycin. The results showed a response rate of 79% for the sulfadiazine association and a high failure rate in the clindamycin group. Side effects with sulfadiazine were slightly more frequent, but with desensitization protocols discontinuation was kept down. The combination of pyrimethamine and sulfadiazine, associated, when necessary, with desensitization schedules, was confirmed to be first choice therapy for cerebral toxoplasmosis in AIDS patients. The role of alternative regimens needs further evaluation.

[Hepatitis and drug addiction: clinical and immunological studies]. / Epatite e farmacodipendenza: considerazioni cliniche ed immunologiche.

The association drug addiction-hepatitis has so increased in recent years to represent a social epidemiological and clinical problem all over the world. Although the clinical picture of hepatitis is already well defined in drug-abusers, it remains to be completely understood the mechanism responsible for the significant incidence of progression from acute to chronic hepatitis in this population. The viral infection, the drug itself, the drug contaminants, the immunological defects (cellular and/or humoral) may be considered as possible contributing factors to this event. For this reason the Authors have performed an immunological study either in a group of drug-abusers with acute and chronic hepatitis, or in a group of 82 "asymptomatic" drug addicts without a history of liver diseases. The results of this study are the following: - In all the drug-addicts considered there is a common contact with virus B. - There are significant alternations of the cellular and humoral immunity in drug-addicts with acute and chronic hepatitis. - In the "asymptomatic" group the humoral immunity is slightly altered (hyper IgM, circulating immunocomplexes), while normal the cellular response. All these findings are critically evaluated also in respect with the new immunopathological mechanisms of hepatitis B.

Indicative morphological myelodysplastic alterations of bone marrow in overt AIDS.

In HIV infection, numerous alterations of the hematopoietic system, with frequent cytopenias in peripheral blood and dysplasia of the bone marrow, have been observed. In order to assess the incidence of the myelodysplastic anomalies, 69 bone marrow aspirate smears from 47 patients with group IV HIV infection, as classified by CDC, have been studied. Various degrees of myelodysplastic alterations were found in all cases; however, dysgranulopoiesis was more frequent and more accentuated than other kinds of dyshematopoiesis. Intense vacuolization, especially in the granuloblastic series, was very frequent. It is felt that a bone marrow configuration that is highly indicative of overt AIDS can be sketched. The human immune deficiency virus may be either directly or indirectly responsible for myelodysplastic alterations.

Prognostic factors of early fatal outcome and long-term survival in patients with Pneumocystis carinii pneumonia and acquired immunodeficiency syndrome.

Fifty-five episodes of Pneumocystis carinii pneumonia (PCP) in AIDS patients were evaluated to assess clinical and laboratory risk factors predicting the probability of surviving the acute episode of PCP and the long-term survival after PCP. Age > 45 yrs, PaO2 < 50 mmHg, AaPO2 > 50 mmHg, and LDH > 800 IU/L correlated strongly with early mortality; patients who needed mechanical ventilation had a significantly lower PaO2 and serum albumin, and higher AaPO2 and LDH compared to the patients who did not. Neither age nor PaO2, AaPO2, LDH, albumin, days from onset, time for recovery, CD4+ cell count correlated with long-term survival of AIDS patients with PCP. Informations obtained at initial presentation of PCP may predict early outcome and influence therapeutic approach, improving chances for survival.