Antiretroviral therapy for HIV infection in 1996. Recommendations of an international panel. International AIDS Society-USA

We report on a retrospective study evaluating infectious morbidity associated with totally implantable venous access devices (TIVAD) (Port-A-Cath) in HIV-infected patients. This study of 84 consecutive HIV-infected patients requiring 89 TIVAD between January 1990 and October 1993 was performed in the Department of Infectious Diseases H?pital de l'Institut Pasteur, Paris, France. The total number of catheter days was 11,595. Eighteen of 89 patients with TIVAD (20%) were infected, causing 25 infectious events (25/89: 28%) among 17 different patients (17/84: 20%). The infection rate was 0.22 per 100 catheter days. Mean onset of infection was 82 days. Twenty microorganisms were isolated: Staphylococcus aureus in eight cases (40%), coagulase-negative Staphylococcus in six cases (30%), Streptococcus D faecalis in one case; Gram-negative bacilli were found in five cases (25%). All patients received an intravenous antibiotherapy combined with a local lock treatment in eight cases. Nine TIVAD removals were performed. One death was related to the TIVAD infection. No additional predisposing factor for infection was identified other than the implied condition of the HIV infection. The population and material in this study were homogeneous. The TIVAD infection rate was comparable to other published reports. Prospective evaluation comparing tunneled catheter and TIVAD in HIV-infected patients is needed.     

Drug therapy of patients treated in hospitals for duodenal ulcers

Drug therapy in hospitalized patients treated for duodenal ulcer disease was reviewed retrospectively. The information was obtained by the means of a medical audit of patient records indexed by the discharge diagnosis of duodenal ulcers. A total of 485 cases were abstracted. Antacids were found to be the cornerstone of duodenal ulcer drug therapy. Anticholinergic drugs occupied a central role throughout the medical treatment of duodenal ulcers. The investigators identified a need for the dissemination of information concerning the use of anticholinergics in duodenal ulcer patients experiencing the complications of hemorrhage and obstruction.     

Manufacturing visions of society and history in textbooks

Interviews with personnel involved in designing secondary-school social-science textbooks, and the findings of previous research in the sociology of work in mass media organizations, reveal three, often complementary, domains of control that influence textbook visual content: (a) industrial - the meaning, relevance, and historical or social significance of an image directed through captioning and accuracy guidelines; (b) commercial - marketing pressures that make aesthetic appeal of great importance to the textbook's production success; and social - interest groups that influence the visual components of the textbook, but because of space limitations the game is zero-sum. This study finds that, in all, the textbook vision of society is homogenized and sanitized to reduce the risk of controversy.     

Temporal analyses of virus replication, immune responses, and efficacy in rhesus macaques immunized with a live, attenuated simian immunodeficiency virus vaccine

Despite evidence that live, attenuated simian immunodeficiency virus (SIV) vaccines can elicit potent protection against pathogenic SIV infection, detailed information on the replication kinetics of attenuated SIV in vivo is lacking. In this study, we measured SIV RNA in the plasma of 16 adult rhesus macaques immunized with a live, attenuated strain of SIV (SIVmac239Deltanef). To evaluate the relationship between replication of the vaccine virus and the onset of protection, four animals per group were challenged with pathogenic SIVmac251 at either 5, 10, 15, or 25 weeks after immunization. SIVmac239Deltanef replicated efficiently in the immunized macaques in the first few weeks after inoculation. SIV RNA was detected in the plasma of all animals by day 7 after inoculation, and peak levels of viremia (10(5) to 10(7) RNA copies/ml) occurred by 7 to 12 days. Following challenge, SIVmac251 was detected in all of the four animals challenged at 5 weeks, in two of four challenged at 10 weeks, in none of four challenged at 15 weeks, and one of four challenged at 25 weeks. One animal immunized with SIVmac239Deltanef and challenged at 10 weeks had evidence of disease progression in the absence of detectable SIVmac251. Although complete protection was not achieved at 5 weeks, a transient reduction in viremia (approximately 100-fold) occurred in the immunized macaques early after challenge compared to the nonimmunized controls. Two weeks after challenge, SIV RNA was also reduced in the lymph nodes of all immunized macaques compared with control animals. Taken together, these results indicate that host responses capable of reducing the viral load in plasma and lymph nodes were induced as early as 5 weeks after immunization with SIVmac239Deltanef, while more potent protection developed between 10 and 15 weeks. In further experiments, we found that resistance to SIVmac251 infection did not correlate with the presence of antibodies to SIV gp130 and p27 antigens and was achieved in the absence of significant neutralizing activity against the primary SIVmac251 challenge stock.     

The time span between symptom onset and starting treatment in head and neck tumors

The interval between the onset of symptoms in patients with head and neck cancers and the introduction of treatment was evaluated. During a 1-year period, patients were interviewed to determine the duration of any delays from the onset of complaints until the first visit to a doctor. Also asked was how long it took to be referred to an ENT specialist and actual referral to our department. We then determined the interval from diagnosis to the introduction of therapy. It was found that the delay of patients who went directly to an otorhino-laryngologist was shorter (median, 8 weeks) than that of patients who first went to their family doctors (median, 13 weeks) (P < 0.02). The latter then took an additional 4 weeks before sending patients to an otorhinolaryngologist. Referral from the ENT specialist to our department took another 2 weeks, as well as our staging and pre-therapeutic management. Our findings show that the patient himself is the critical factor in delaying diagnosis and therapy. Tumor patients with greater professional qualification went to their doctors earlier (P < 0.0001) or more often went directly to an ENT specialist (P < 0.002). Consultations of physicians without experience in otorhinolaryngology caused yet further delays.     

Cloning and characterization of the gene encoding 1-cyclohexenylcarbonyl coenzyme A reductase from Streptomyces collinus

We report the cloning of the gene encoding the 1-cyclohexenylcarbonyl coenzyme A reductase (ChcA) of Streptomyces collinus, an enzyme putatively involved in the final reduction step in the formation of the cyclohexyl moiety of ansatrienin from shikimic acid. The cloned gene, with a proposed designation of chcA, encodes an 843-bp open reading frame which predicts a primary translation product of 280 amino acids and a calculated molecular mass of 29.7 kDa. Highly significant sequence similiarity extending along almost the entire length of the protein was observed with members of the short-chain alcohol dehydrogenase superfamily. The S. collinus chcA gene was overexpressed in Escherichia coli by using a bacteriophage T7 transient expression system, and a protein with a specific ChcA activity was detected. The E. coli-produced ChcA protein was purified and shown to have similar steady-state kinetics and electrophoretic mobility on sodium dodecyl sulfate-polyacrylamide gels as the enoyl-coenzyme A reductase protein prepared from S. collinus. The enzyme demonstrated the ability to catalyze, in vitro, three of the reductive steps involved in the formation of cyclohexanecarboxylic acid. An S. collinus chcA mutant, constructed by deletion of a genomic region comprising the 5' end of chcA, lost the ChcA activity and the ability to synthesize either cyclohexanecarboxylic acid or ansatrienin. These results suggest that chcA encodes the ChcA that is involved in catalyzing multiple reductive steps in the pathway that provides the cyclohexanecarboxylic acid from shikimic acid.     

B lymphocytes induce the formation of follicular dendritic cell clusters in a lymphotoxin alpha-dependent fashion

Lymphotoxin (LT)alpha is expressed by activated T cells, especially CD4(+) T helper type 1 cells, and by activated B and natural killer cells, but the functions of this molecule in vivo are incompletely defined. We have previously shown that follicular dendritic cell (FDC) clusters and germinal centers (GCs) are absent from the peripheral lymphoid tissues of LTalpha-deficient (LTalpha-/-) mice. LTalpha-/- mice produce high levels of antigen-specific immunoglobulin (Ig)M, but very low levels of IgG after immunization with sheep red blood cells. We show here that LTalpha-expressing B cells are essential for the recovery of primary, secondary, and memory humoral immune responses in LTalpha-/- mice. It is not necessary for T cells to express LTalpha to support these immune functions. Importantly, LTalpha-expressing B cells alone are essential and sufficient for the formation of FDC clusters. Once these clusters are formed by LTalpha-expressing B cells, then LTalpha-deficient T cells can interact with B cells to generate GCs and productive class-switched antibody responses. Thus, B cells themselves provide an essential signal that induces and maintains the lymphoid microenvironment essential for GC formation and class-switched Ig responses.     

Effects of silica exposure on substance P immunoreactivity and preprotachykinin mRNA expression in trigeminal sensory neurons in Fischer 344 rats

Trigeminal sensory neurons innervate the nasal cavity and may release substance P (SP) upon exposure to inhaled irritants. The purpose of this study was to determine if silica dust, an occupational irritant causing inflammation, activates sensory neurons supplying the nasal cavity. Male Fischer 344 rats were placed in inhalation chambers and exposed daily to 2 mg/m3 of fresh silica (average diameter 1 microm) for 6 mo. Following exposure, the trigeminal ganglia (TG) were removed and prepared for SP immunocytochemistry and for preprotachykinin (PPT) autoradiographic in situ hybridization. The SP-like immunofluorescence in TG neurons was subjectively categorized as high, moderate, or low (background) intensity. In situ hybridization autoradiographs were quantified on the basis of grain density using digital imaging analysis. The SP immunoreactivity and PPT mRNA expression in the TG neurons were significantly increased after silica inhalation. The proportion of highly positive SP-immunoreactive neurons shifted from 1.30 +/- 0.58% in controls to 11.30 +/- 1.15% after silica treatment. The neurons exhibiting high grain density for PPT mRNA increased from 1.50 +/- 0.87% in controls to 11.67 +/- 0.58% in the silica group. Thus, inhalation of silica causes upper airway irritation resulting in increased levels of immunoreactive neuronal SP and PPT mRNA. These findings suggest that silica activates sensory pathways that may be involved in nasal inflammation.