Precursors of arteriosclerosis in childhood. Protocol and firsts results concerning plasma lipids and carbohydrate tolerance in 520 school children at Pordenone (Italy) (author's transl)]

The cardiological centers of Pordenone and Cittadella (Italy) organized by the Institute of Clinica Medica II of Padua University, have carried out a study on the "Precursors of arteriosclerosis in children", according to a WHO protocol. In this paper some results of the Pordenone study are reported, concerning serum cholesterol (TC), triglycerides (TG) and blood glucose 1 h after 1 g/Kg glucose per os. 520 school children, males and females, aged 6, 9, 12, 15 years, entered the study. Mean serum TC resulted significantly higher at age 12 as compared to the other age classes. Serum TG progressively increased with age. Mean serum TC and TG in our italian children and adolescents were silimar to those reported in studies from other countries. Blood glucose resulted significantly higher in children than in adolescents. The distribution of the blood glucose values was bimodal. After having arbitrarily fixed cut-off points for serum TC, TG and blood glucose, the prevalence of hyperlipidemia and hyperglycemia was determined. The prevalence figures have shown that at the pediatric age it is possible to identify subjects at "risk" of developing arteriosclerosis.     

Monitoring and management of antituberculosis drug induced hepatotoxicity

BACKGROUND: Hepatotoxicity to antituberculosis therapy (ATT) poses a major challenge. This often results in inadequate therapy. The risk of fulminant hepatic failure and mortality is high once icteric hepatitis develops. There is no consensus on monitoring protocols and for the reintroduction of ATT. METHODS: All patients (from the Department of Internal Medicine and Gastroenterology, Jagjivanram Hospital and the Department of Gastroenterology, Bombay Hospital, Mumbai, India) with a diagnosis of tuberculosis, who were to receive ATT during the study period, were included in the present study for prospective periodic laboratory monitoring for the development of hepatotoxicity. Those patients who developed hepatotoxicity formed Group A (n = 21), whereas those who did not develop hepatotoxicity were included in Group C (n = 179). For the purpose of comparison with Group A, all the patients who presented directly with ATT induced hepatotoxicity during the study period were categorized as Group B (n = 24). Group A and B were further studied after normalization of liver functions for sequential reintroduction with therapeutic doses at a weekly interval. RESULTS: In Group A, 66.6% (14 patients) of the patients were diagnosed in the asymptomatic period. Seven patients had symptomatic hepatitis, but none had icteric illness. There were no mortalities in Group A. In contrast, all the patients in Group B had symptomatic hepatitis (75% icteric hepatitis). There was a mortality rate of 16.6% (four patients). Of the 41 patients from Groups A and B who survived, reintroduction was successful in 38/39 (97.4%). In the remaining two patients who were in Group B, reintroduction was not attempted because of decompensated liver disease. CONCLUSIONS: Periodic laboratory monitoring is important in detecting hepatotoxicity at an early stage, thereby preventing mortality. Sequential reintroduction is often successful.     

The importance of timing in melatonin administration in a blind man

An 18-year-old blind man suffered from chronic sleep disturbances associated with daytime fatigue and excessive daytime somnolence. After two unsuccessful treatment regimens with 5 mg and 10 mg melatonin administered at bedtime (2200-2230), a third regimen of 5 mg melatonin administered at 2000 for 3 weeks resulted in a successful resolution of his sleep disturbances. We suggest that the efficacy of melatonin in ameliorating sleep disturbances because of alterations in circadian rhythmicity may be dependent on the time of administration.     

Role of oligosaccharides in the processing and maturation of envelope glycoproteins of human immunodeficiency virus type 1.

The processing and maturation of envelope glycoproteins of human immunodeficiency virus type 1 (HIV-1) were studied in infected cells treated with inhibitors of oligosaccharide processing. In MOLT-3 cells chronically infected with HIV-1 (strain HTLV-IIIB), tunicamycin severely inhibited the glycosylation of envelope proteins. Deoxynojirimycin, an inhibitor of glucosidase I in the rough endoplasmic reticulum, inhibited the proteolytic processing of gp160, whereas no such effect was noted with either deoxymannojirimycin or swainsonine, inhibitors of mannosidase I and II, respectively, in the Golgi complex. The processed gp120 and gp41 synthesized in the presence of deoxymannojirimycin were found to contain mannose-rich oligosaccharide cores as evidenced by their susceptibility to endoglycosidase H digestion. The formation of syncytia normally observed when CEM cells are cocultured with HIV-1-infected cells was markedly inhibited in the presence of deoxynojirimycin, but such inhibition was not observed in cells treated with deoxymannojirimycin or swainsonine. The infectivity of virions released from MOLT-3/HTLV-IIIB cells treated with deoxynojirimycin or deoxymannojirimycin was significantly lower than the infectivity of virions released from untreated cells. On the other hand, treatment with swainsonine did not affect the infectivity of the progeny virus. These results suggest that the proteolytic processing of gp160 takes place in infected cells when the glycoprotein has mannose-rich oligosaccharide structures. Trimming of glucose residues and the primary trimming of mannose residues are necessary for the release of infectious virus.     

Acute-phase reactants during murine tuberculosis: unknown dimensions and new frontiers

SETTING: Serum amyloid P-component (SAP) plays important roles in host defense during various infectious diseases; however, nothing is known in tuberculosis (TB). OBJECTIVE: To study the SAP response of Mycobacterium tuberculosis H37Rv- and H37Ra-infected mice, and to determine the effect(s) of purified mouse SAP both on their intra-alveolar macrophage (AM) uptake and intra-AM growth in vitro. DESIGN: The SAP levels of mice intratracheally infected with M. tuberculosis H37Rv and H37Ra were determined by ELISA. Mycobacterial AM uptake and intra-AM growth in vitro were determined using fluorescence microscopy and plating, respectively. RESULTS: M. tuberculosis H37Rv-infected mice showed significantly (p < 0.05) increased SAP levels (352.8+/-36.1 microg/ml) with compared mice infected with M. tuberculosis H37Ra (170+/-18.5 microg/ml). During the acute phase of both these infections, enhanced SAP levels correlated with the lung mycobacterial load. In vitro, purified mouse SAP (1-80 microg/ml) inhibited the AM uptake of both the mycobacteria in a concentration-dependent manners to a similar extent; 20 microg/ml SAP appeared optimal. Mycobacterial uptake inhibition was divalent cation- and pH-dependent, and was unaffected both by heat-inactivated and deglycosylated SAP, separately. Curiously, purified mouse SAP (1-80 microg/ml), in a concentration-dependent manner, inhibited the intra-AM growth of both M. tuberculosis H37Rv and H37Ra in vitro; the effect was 0.8 log10 CFUs greater on the latter. Both the mannose-based simple sugars and rabbit anti-mouse SAP polyclonal antibody, separately, annulled the inhibition of mycobacterial growth in vitro. CONCLUSION: This initial study demonstrates that both the SAP response of M. tuberculosis-infected mice, and the SAP-induced intra-AM mycobacterial growth inhibition in vitro were apparently dependent on mycobacterial virulence.     

Profound loss of T-cell receptor repertoire complexity in cutaneous T-cell lymphoma

Cutaneous T-cell lymphoma (CTCL) is a malignancy of skin-homing T cells. A major feature of CTCL is profound immunosuppression, such that patients with advanced mycosis fungoides or Sézary syndrome have been compared with patients with advanced HIV disease and are susceptible to opportunistic infection. The etiology of this immunosuppression is unclear. We analyzed peripheral blood T cells of patients with CTCL with stage I to IV disease, using a sensitive beta-variable complementarity-determining region 3 spectratyping approach. Our data revealed a profound disruption of the complexity of the T-cell repertoire, which was universally observed in patients with advanced disease (stages III and IV), and present in up to 50% of patients with early-stage disease (stages I and II). In most patients, multiple monoclonal and oligoclonal complementarity-determining region 3 (CDR3) spectratype patterns in many different beta-variable families were seen. Equally striking was a reduction of normal T cells (as judged by absolute CD4 counts) across multiple beta-variable families. In general, CTCL spectratypes were reminiscent of advanced HIV spectratypes published elsewhere. Taken together, these data are most consistent with a global assault on the T-cell repertoire in patients with CTCL, a process that can be observed even in early-stage disease.     

Weighted Coherence: A More Effective Measure Than Average Coherence

In this study, we evaluated the effectiveness of the statistic, Weighted Coherence in relation to the average or mean coherence in a particular frequency band after cross-spectral analysis. In time domain, correlation coefficient explains the relationship between two variables of interest, and a similar statistic in frequency domain using cross-spectral analysis is referred to as coherence, which is equivalent to the squared correlation coefficient and ranges from zero to unity. In this study, we show that weighted coherence is much more sensitive to various challenges within the same subject and also may be a more sensitive indicator of group differences in different frequency bands. Our data on normal subjects and patients with panic disorder during supine and standing postures during normal breathing, and also at different breathing rates throw new light on the sensitivity of this previously described novel index to quantify coherence between two related time series such as beat-to-beat heart rate and QT interval.