Adverse drug reactions in patients admitted to hospital identified by discharge ICD-10 codes and by spontaneous reports.

AIMS: We studied the international classification of disease (ICD) hospital discharge codes to find unreported adverse drug reactions (ADRs), and asked doctors about their attitudes to reporting some of these cases. METHODS: We examined the ICD codes assigned on discharge to identify ADRs and compared these with spontaneous reports made to the Committee on Safety of Medicines (CSM). Doctors involved were sent brief résumés of cases and asked if they would report them. RESULTS: 49 of 21 365 patient episodes were coded on discharge as ADRs, of which 33 were 'reportable'. Fourteen spontaneous reports were received by the CSM during the same period. The two groups did not overlap. 25 of 60 doctors responded to our questionnaire, and would have reported only 8 of 75 cases outlined. CONCLUSIONS: The ICD coding allowed us to identify important ADRs which most doctors would not report spontaneously.

Induction of humoral and cell-mediated anti-human immunodeficiency virus (HIV) responses in HIV sero-negative volunteers by immunization with recombinant gp160.

Development of an effective vaccine for prevention of infection with HIV would provide an important mechanism for controlling the AIDS epidemic. In the current study, the first clinical trial of a candidate HIV-1 vaccine initiated in the United States, the safety and immunogenicity of escalating doses (10-1,280 micrograms) of recombinant gp160 (rgp160), were evaluated in 138 HIV-negative volunteers. Maximal antibody responses, as evaluated by ELISA, were seen after immunization with three doses of 1,280 micrograms rgp160. Responses to some specific epitopes of HIV gp160, including the second conserved domain and the CD4 binding site, were seen more frequently than after natural infection. Neutralizing antibodies to the homologous HIV strain, but not heterologous strains, were induced by this regimen. Blastogenic responses to rgp160 were seen in most volunteers receiving at least two doses of > or = 20 micrograms. These envelope-specific T cell responses were also seen against heterologous strains of HIV. No major adverse reactions were seen after immunization. Thus, rgp160 is a safe and immunogenic candidate HIV vaccine; further studies are needed to determine if it will provide any clinical benefit in preventing HIV infection.

Indeterminate western blot patterns in a cohort of individuals at high risk for human immunodeficiency virus (HIV-1) exposure.

Our objective was to map serial patterns of Western blot reactivity over time of a cohort of initially ELISA-negative, Western blot-indeterminate individuals from a high-risk group and to determine if these individuals were at increased risk of harboring occult HIV-1 infection. A 2-year prospective study used serial ELISA, two types of Western blot, immunologic profiles, HIV-1 culture, and analysis by polymerase chain reaction. Subjects were 20 ELISA-negative, Western blot indeterminate homosexual volunteers and 20 matched seronegative controls. Results showed that 19 of 20 study subjects completed a mean of 17.0 months of clinical and laboratory follow-up. Reactivities with p24 and/or with p55 were the two most commonly observed Western blot patterns, occurring in 70% of individuals. Specific Western blot reactivity was dependent upon the particular immunoblot preparation being used and varied considerably on a longitudinal basis. No individual pattern appeared predictive of an increased likelihood of subsequent seroconversion to HIV-1 relative to controls. By all other criteria including polymerase chain reaction analysis, samples from 17 of 19 individuals remained negative for HIV-1 at each time point. Two individuals evolved from an indeterminate to a positive Western blot and, simultaneously, from a negative to a positive polymerase chain reaction analysis, during follow-up. Our conclusions were as follows. ELISA-negative, Western blot-indeterminate individuals from a high-risk group show marked variability in immunoblot findings over time, and these patterns do not appear predictive of an increased likelihood of infection.(ABSTRACT TRUNCATED AT 250 WORDS)

The detection of Salmonella enteritidis and S. typhimurium using immunomagnetic separation and conductance microbiology.

A rapid method for detection of Salmonella in milk powder is described. The technique involves immunomagnetic separation of Salmonella from pre-enrichment broths using new commercially-available materials, and detection using conductance measurements. Salmonella detection was enhanced by reducing the number and types of competing bacteria present and concentrating the number of Salmonella in the final assay. After a 6 h pre-incubation period Salmonella enteritidis, from an initial inoculum size of 20 cells/ml, were detected in 7.5 h by conductance.

Modelling the effect of pH, acidulant and temperature on the growth rate of Yersinia enterocolitica.

Growth of two pathogenic and one environmental serotype of Yersinia enterocolitica under acidic conditions and at 4 and 25 degrees C was investigated. At both temperatures the maximum growth inhibitory pH depended on the acidulant used and was in the order acetic greater than lactic greater than citric greater than sulphuric. At the lower temperature the maximum growth inhibitory pH was 0.3-0.5 pH units higher than at 25 degrees C. No difference was observed between the behaviour of pathogenic and environmental serotypes in this respect. Measurement of growth at a number of sub-optimal temperatures and pH values showed that the variation of growth rate with temperature could be represented by a square root plot. The effect of different pH values could be incorporated into the model by replacing the regression coefficient b by its relationship with pH. Values of maximum growth inhibitory pH derived from the model were in good agreement with experimental values with the exception of acetic acid.

Syngeneic bone marrow transplantation and adoptive transfer of peripheral blood lymphocytes combined with zidovudine in human immunodeficiency virus (HIV) infection.

OBJECTIVE: To examine the role of syngeneic bone marrow transplantation and peripheral blood lymphocyte infusions combined with zidovudine in the treatment of patients with human immunodeficiency virus (HIV) infection. DESIGN: A partially randomized outpatient trial. SETTING: Outpatient and inpatient facility of the Clinical Center of the National Institutes of Health, a research-based referral facility. PATIENTS: Sixteen patients with HIV infection (15 symptomatic, 1 asymptomatic). INTERVENTIONS: Symptomatic patients were treated with zidovudine, 500 mg orally every 4 hours for 12 weeks, combined with six peripheral blood lymphocyte infusions (four at week 10, two at week 12) and bone marrow transplantation (at week 12) using HIV-seronegative identical twins as donors. After transplantation, patients were randomly assigned to receive either zidovudine, 100 mg every 4 hours, or placebo for 12 months. The asymptomatic patient received zidovudine for the first 12 weeks, discontinuing therapy after transplantation. Immunologic and virologic monitoring were done monthly. MEASUREMENTS AND MAIN RESULTS: Immediately after lymphocyte infusions and bone marrow transplantation, there was an increase in the mean (+/- SE) CD4 cell percent (19.1% +/- 3.1% to 28.1% +/- 3.0%), an increase in the fraction of patients with delayed-type hypersensitivity responses to tetanus toxoid (4 of 13 to 11 of 13) and the development of delayed-type hypersensitivity to keyhole-limpet hemocyanin (a primary immunogen to which only the donor had been immunized) in 8 of 12 patients tested. No significant clinical improvement was noted, however, and there was no overall sustained immunologic improvement. No differences in CD4 cell percents, delayed-hypersensitivity skin tests, HIV cultures, or p24 antigenemia were seen between patients treated with zidovudine or placebo after transplantation. CONCLUSIONS: Although they establish the feasibility of combining zidovudine with cellular immune reconstitution in treating patients with HIV infection, our results show that any benefits from such combination therapy are at best transient. Future attempts at cellular immune reconstitution may need to use improved antiretroviral regimens as well as immunization of donors with HIV-specific antigens.

A phase I trial of recombinant human interferon-gamma in patients with Kaposi's sarcoma and the acquired immunodeficiency syndrome (AIDS).

A Phase I study of recombinant interferon-gamma (rIFN-gamma) was conducted to determine the toxicity and pharmacokinetics of this lymphokine in acquired immunodeficiency syndrome (AIDS) patients with Kaposi's sarcoma (KS). Sixteen patients with AIDS/KS were entered into a fixed-dose trial at either 0.001, 0.01, 0.1, or 1.0 mg/m2 of rIFN-gamma. rIFN-gamma was initially administered either as a single 24-hr continuous iv infusion or as a single im injection, followed 4 days later by a 10-day course of daily therapy by the same route. Following a 1-week washout period, this sequence of administration was then repeated, with the drug given by the alternate route. Pharmacokinetic analysis of the 1.0-mg/m2 group revealed that peak serum levels of up to 153 U/ml occurred 2-4 hr after im injection and that steady-state levels of up to 40 U/ml were reached approximately 7-12 hr after beginning iv infusion. Dose-related toxicities in this trial included fever, headache, fatigue, nausea, and hepatitis, all of which were most severe at the two highest doses. Dose-dependent depression of the total white blood-cell (WBC) count, affecting both granulocytes and lymphocytes, was the most common laboratory abnormality. Natural killer (NK)-cell activity was slightly enhanced at a dose of 0.1 mg/m2 but suppressed at 1.0 mg/m2 of drug; monocyte-mediated cytotoxicity, in contrast, was significantly increased only at the highest dose. No dose-related changes were noted in KS lesions, HLA-DR expression by peripheral blood mononuclear cells, lymphocyte blastogenesis, or the ability to culture cytomegalovirus (CMV) from body fluids. We conclude that a maximally tolerated dose (MTD) for this drug is in the range of 0.1-1.0 mg/m2 and that at least modest evidence of systemic immunomodulation may be seen when rIFN-gamma is given at doses at or near this MTD.

Rapid and automated detection of salmonella by electrical measurements.

A rapid method for determining the presence of salmonella in food is described. It consists of pre-enrichment in buffered peptone water modified by the addition of dulcitol and trimethylamine oxide, followed by selective enrichment in a selenite-cystine broth with similar modifications. Changes in the conductance of the selective enrichment broth are monitored continuously using a suitable impediometric instrument. Most of the Salmonella spp. tested gave a fast (approximately 100 microS/h) and large (greater than 600 microS) change in conductance, other enteric bacteria much less or no change. The assay is usually complete within 24 h. Samples of foodstuffs, naturally and artificially contaminated with Salmonella spp., were all correctly classified. Some strains of Citrobacter freundii produced a false positive conductance response, and they could not be selectively eliminated using antibiotics or cyanide. The conductance method is simple and easy to use, gives rapid results and involves less media and subculturing than is required for traditional methods.