The interaction in vitro between polymorphonuclear leukocytes and mycoplasma.

The interaction, between mycoplasma (PPLO) and human or rabbit leukocytes was examined in vitro. Upon incubation of M. hominis or M. arthritidis for 2 hr with rabbit peritoneal exudate granulocytes or leukocytes from human peripheral blood, no killing of mycoplasma was observed either in the presence or absence of type-specific antiserum. However, (14)CO(2) production from glucose-1-(14)C was stimulated up to 10-fold in the presence of live or heat-killed PPLO. The extent of stimulation depended upon the number of organisms and the presence of type-specific antiserum. The stimulation of (14)CO(2) production seems not because of tight adherence of PPLO to the leukocytes, since PPLO were quantitatively recovered in the medium after sedimenting the granulocytes. The enhanced conversion of medium lysolecithin to cellular lecithin that accompanies phagocytosis of polystyrene particles was significantly reduced when PPLO were also present. Mycoplasma alone elicited no stimulation of lecithin formation. Killing of E. coli, a microorganism readily engulfed and killed by leukocytes in vitro, was diminished when the leukocytes were preincubated with mycoplasma. These findings indicate that M. hominis and M. arthritidis are not ingested by granulocytes to any detectable extent, but that these organisms affect the leukocytes' metabolism and also impair phagocytosis of E. coli.

Studies of PPLO infection. V. Inhibition of lymphocyte mitosis and antibody formation by mycoplasmal extracts.

Extracts of five arginine-utilizing mycoplasmas inhibit PHA-induced lymphocyte mitosis, while extracts of five glucose-utilizing mycoplasmas do not. Evidence is presented supporting the view that the inhibitory factor is the enzyme arginine deiminase. This enzyme inhibits the reactions of human lymphocytes to antigens as well as PHA, and the secondary production of antibody by rabbit lymph node fragments in vitro. Addition of enzyme to the cells several days after the initial mitotic or antigenic stimulus reduces, but does not abolish, further cellular activity. The production of serum proteins by hepatoma cells is totally unaffected by the mycoplasmal extract. It is concluded that arginine is an essential amino acid for the small lymphocyte, but not for the transformed cell nor for a number of other cell types. Suggestive evidence has been obtained that other enzymes similarly affect lymphocyte reactions.

A vaccine to prevent herpes zoster and postherpetic neuralgia in older adults.

BACKGROUND: The incidence and severity of herpes zoster and postherpetic neuralgia increase with age in association with a progressive decline in cell-mediated immunity to varicella-zoster virus (VZV). We tested the hypothesis that vaccination against VZV would decrease the incidence, severity, or both of herpes zoster and postherpetic neuralgia among older adults. METHODS: We enrolled 38,546 adults 60 years of age or older in a randomized, double-blind, placebo-controlled trial of an investigational live attenuated Oka/Merck VZV vaccine ("zoster vaccine"). Herpes zoster was diagnosed according to clinical and laboratory criteria. The pain and discomfort associated with herpes zoster were measured repeatedly for six months. The primary end point was the burden of illness due to herpes zoster, a measure affected by the incidence, severity, and duration of the associated pain and discomfort. The secondary end point was the incidence of postherpetic neuralgia. RESULTS: More than 95 percent of the subjects continued in the study to its completion, with a median of 3.12 years of surveillance for herpes zoster. A total of 957 confirmed cases of herpes zoster (315 among vaccine recipients and 642 among placebo recipients) and 107 cases of postherpetic neuralgia (27 among vaccine recipients and 80 among placebo recipients) were included in the efficacy analysis. The use of the zoster vaccine reduced the burden of illness due to herpes zoster by 61.1 percent (P<0.001), reduced the incidence of postherpetic neuralgia by 66.5 percent (P<0.001), and reduced the incidence of herpes zoster by 51.3 percent (P<0.001). Reactions at the injection site were more frequent among vaccine recipients but were generally mild. CONCLUSIONS: The zoster vaccine markedly reduced morbidity from herpes zoster and postherpetic neuralgia among older adults.

Hepatitis associated with high-dose oxacillin therapy.

A prospective survey of liver function during oxacillin sodium therapy revealed five cases of drug-related abnormalities among 41 patients. In each instance, the serum transaminase level was increased from normal to greater than 100 units. The serum alkaline phosphatase level was mildly elevated and bilirubin levels remained normal. All of the patients were asymptomatic. Hepatic dysfunction was reversible on withdrawal of oxacillin therapy and substitution of a cephalosporin or clindamycin. The observed abnormalities in liver function were associated with a daily oxacillin sodium dose of greater than or equal to 12 gm as well as with heroin addiction and staphylococcal endocarditis.

Racial differences in care among hospitalized patients with Pneumocystis carinii pneumonia in Chicago, New York, Los Angeles, Miami, and Raleigh-Durham.

BACKGROUND: While strategies for medical care for human immunodeficiency virus-related Pneumocystis carinii pneumonia (PCP) are well established, racial variations in care have not been evaluated. OBJECTIVE: To determine whether sociodemographic characteristics influence patterns of care and patient outcomes, by analyzing the use of diagnostic tests and anti-PCP medications and in-hospital mortality rates for persons who were hospitalized with human immunodeficiency virus-related PCP. METHODS: Retrospective chart review of a cohort of 627 Veterans Administration (VA) patients and 1547 non-VA patients with empirically treated or cytologically confirmed PCP who were hospitalized from 1987 to 1990. Outcomes included representative aspects of the process of care for PCP and short-term mortality rates. RESULTS: Among VA patients, black and Hispanic patients were not significantly different from white patients with regard to in-hospital mortality rates, use and timing of a bronchoscopy, or receipt of timely anti-PCP medications. Among non-VA patients, black and Hispanic patients were more likely to die in the hospital and less likely to undergo a diagnostic bronchoscopy in the first 2 days of hospitalization. These racial and ethnic group differences in the use of a bronchoscopy and in-hospital mortality among non-VA patients were almost fully accounted for by differences in health insurance status and hospital characteristics. CONCLUSIONS: Racial factors do not appear to be an important determinant of the intensity of diagnostic or therapeutic care among patients who are hospitalized with PCP. Variations in care are largely attributable to differences in health insurance and admitting hospital characteristics.

Site of disease and opportunistic infection predict survival in HIV-associated tuberculosis.

OBJECTIVE: Infection with HIV adversely affects survival in patients with tuberculosis (TB), even when TB is effectively treated. The aim of this study was to identify the determinants of survival in HIV-associated TB. DESIGN: Retrospective cohort study. SETTING: Four US academic medical centers. PATIENTS: An inception cohort of 112 HIV-infected patients (mean age 41 years, 96% men, 46% African American) with their first episode of culture-proven TB. OUTCOMES MEASURES: Observed survival from the date of diagnosis of TB to the date of death or censoring. Independent variables included demographics, HIV-related conditions, risk behavior for HIV, absolute CD4+ counts, and site of disease with Mycobacterium tuberculosis. RESULTS: Of the 112 patients, 54 (48%) had pulmonary TB alone, 36 (32%) had both pulmonary and extra-pulmonary TB and 22 (20%) had extrapulmonary TB alone. Median CD4+ count was 95 x 10(6)/l (range, 2-767 x 10(6)/l). During follow-up, 45 patients (40%) died. Median survival was shortest in patients with both pulmonary and extrapulmonary disease (8.4 months), followed by extrapulmonary disease alone (15.6 months), then pulmonary disease (30.4 months; P < 0.001, log-rank test). Median survival was also reduced in patients with previous opportunistic infection and in those with CD4+ < 200 x 10(6)/l. In a proportional hazards regression analysis, which adjusted for CD4+ count, extrapulmonary disease and previous opportunistic infection were the only factors independently associated with shorter survival. Of the extrapulmonary sites of disease, TB meningitis was associated with the greatest risk of death. CONCLUSION: The site of culture-proven TB at presentation and the history of previous opportunistic infection are important predictors of survival in HIV-infected patients with TB.

Fungal endocarditis: analysis of 24 cases and review of the literature.

Fungal endocarditis occurs in heroin addicts, patients who have undergone cardiovascular surgery, and patients who are treated for prolonged periods with intravenous fluids and broad spectrum antibiotics. The organisms associated with endocardial infection differ in each of these groups. Candida parapsilosis is the fungal species most commonly isolated from narcotics addicts, Aspergillus species are most frequently found in patients after cardiovascular surgery, and Candida albicans occurs most frequently in patients who have received prolonged courses of intravenous fluids and antibiotics. Despite the availability of antifungal antibiotics and surgery, over 80% of patients with documented fungal endocarditis die of this infection. Thus, early diagnosis of fungal invasion and prevention of established endocardial infection are essential. Antifungal therapy and/or careful followup should be considered in patients in whom "transient fungemia" is documented by blood culture and serological and untrasonic techniques should be further evaluated as a means of early diagnosis.

Zidovudine resistance, syncytium-inducing phenotype, and HIV disease progression in a case-control study. The VA Cooperative Study Group.

A case-control study of patients with progressive (cases) or nonprogressive (controls) disease was designed to determine the association among disease progression, zidovudine sensitivity, and syncytium-inducing phenotype. Viral isolates were screened for sensitivity to zidovudine using a peripheral blood mononuclear cell-based assay and for syncytium-inducing (SI) phenotype in MT2 cell culture. Thirty-four patients, whose disease progressed to AIDS or whose CD4 cell numbers fell < 200 cells/mm3, were matched with 34 patients whose conditions had not progressed or whose CD4 cell numbers remained > 200 cells/mm3. Virus was successfully cultured from both the progressor and the nonprogressor in 17 of these 34 matched case-control pairs. In six of the 17 pairs, virus isolated from the progressor had an IC50 (50% inhibitory concentration) for zidovudine > 1 microM and at least threefold greater than the IC50 of virus isolated from the matched nonprogressor (p = 0.04). In 16 of these 17 pairs the virus isolated from the progressor had the SI phenotype, indicative of high cytopathogenicity, while the virus from the matched nonprogressor had a non-syncytium-inducing phenotype (p < 0.0001). Zidovudine therapy did not appear to select for the SI phenotype in this patient population. A statistically significant association between high-level zidovudine resistance and clinical disease progression was demonstrated. A statistically significant association between the SI phenotype and disease progression was demonstrated. The results suggest that disease progression while being treated with zidovudine therapy may be more closely associated with the SI phenotype than with zidovudine resistance.

Subacute and acute endocarditis due to Pseudomonas cepacia in heroin addicts.

Five heroin addicts were treated for endocarditis caused by Pseudomonas cepacia. Two of these infections occurred in patients with no known heart disease whereas the others occurred at sites of previous endocarditis or valve prostheses. Infection was indolent in four patients but was associated with shock and skin lesions suggestive of ecthyma gangrenosum in the fifth. After failure of chloramphenicol and kanamycin, all patients were treated with a combination of sulfamethoxazole, trimethoprim and polymyxin plus heart valve resection or replacement.

Association of teichoic acid antibody with metastatic sequelae of catheter-associated Staphylococcus aureus bacteremia: a failure of the two-week antibiotic treatment.

A patient with Staphylococcus aureus bacteremia associated with an infected intravenous catheter was treated with oxacillin for two weeks. During that period all blood cultures were sterile, he rapidly became afebrile, and there were no signs of endocarditis or metastatic abscesses. However, serum antibodies against staphylococcal teichoic acid, initially undetectable by the agar gel immunodiffusion technic, became positive during the second week of treatment. Three weeks after discharge, the patient was readmitted to the hospital because of back pain and weakness in the lower extremities. Vertebral osteomyelitis and a spinal epidural abscess caused by Staph. aureus of the same phage type as the bacteremic isolate were demonstrated. This case illustrates the importance of careful follow-up of patients with Staph. aureus bacteremia and the potential value of serial measurement of teichoic acid antibodies in detecting clinically inapparent complications of infection.

Preparations for AIDS vaccine trials. Retention, behavior change, and HIV-seroconversion among injecting drug users (IDUs) and sexual partners of IDUs.

The likelihood that subjects in human immunodeficiency virus (HIV) vaccine efficacy trials will alter their behavioral risks for HIV infection over time must be considered in evaluating the feasibility of such trials and in estimating the necessary sample sizes to be enrolled. Potential subjects for future vaccine efficacy trials include injecting drug users (IDUs) and others who may be difficult to retain in studies and who may alter HIV-risk-related behaviors substantially over time. We have investigated behavior change, retention, and HIV seroconversion among 577 New York City resident IDUs and sexual partners of IDUs enlisted between July 1 and December 31, 1992. We attempted to see all subjects every 3 months for interviews, blood donation and HIV testing. We were able to retain 68% of subjects in the study through the third scheduled recall at 7.5-10.5 months after enlistment. HIV seroconversion through March 1, 1994, was 1.33/100 person-years at risk. There was a significant inverse relationship between HIV seroconversion and retention at the 9-month recall after adjusting for age, gender, and the amount of locator information provided by subjects at enlistment. Among subjects seen at each of the scheduled visits at 3, 6, and 9 months after enrollment, modest but statistically significant behavior changes that reduced risk were observed in self-reported drug injection frequency, heroin injection frequency, sexual contact with IDUs, and sharing of needles/syringes. The magnitude of these changes in risk, however, was small and may be transient. The behavior changes observed to date do not appear to be large enough to substantially alter calculations of sample sizes needed in future HIV vaccine efficacy trials.

Using the national registry of HIV-infected veterans in research: lessons for the development of disease registries.

Disease-specific registries have many important applications in epidemiologic, clinical and health services research. Since 1989 the Department of Veterans Affairs has maintained a national HIV registry. VA's HIV registry is national in scope, it contains longitudinal data and detailed resource utilization and clinical information. To describe the structure, function, and limitations of VA's national HIV registry, and to test its accuracy and completeness. The VA's national HIV registry contains data that are electronically extracted from VA's computerized comprehensive clinical and administrative databases, called Veterans Integrated Health Systems Technology and Architecture (VISTA). We examined the number of AIDS patients and the number of new patients identified to the registry, by year, through December 1996. We verified data elements against information obtained from the medical records at five VA sites. By December 1996, 40,000 HIV-infected patients had been identified to the registry. We encountered missing data and problems with data classification. Missing data occurred for some elements related to the computer programming that creates the registry (e.g., pharmacy files), and for other elements because manual entry is required (e.g., ethnicity). Lack of a standardized data classification system was a problem, especially for the pharmacy and laboratory files. In using VA's national HIV registry we have learned important lessons, which, if taken into account in the future, could lead to the creation of model disease-specific registries.

Excess mortality in critically ill patients with nosocomial bloodstream infections.

To determine the excess mortality attributable to hospital-acquired bloodstream infections, we applied the acute physiology and chronic health evaluation (APACHE) II classification to 34 critically ill patients with this complication. The study included primary bloodstream infections, defined by a positive blood culture at least three days after hospitalization, in the absence of any other apparent source of infection. The most frequent blood isolates included Staphylococcus aureus (39 percent), Gram-negative rods (24 percent), and Candida albicans (15 percent); the spectrum of blood isolates suggested that most infections were related to intravascular catheters. In a control group of intensive care unit patients (n = 384), the death rate predicted by APACHE II was similar to the observed death rate (35.3 vs 37.8 percent). In a subgroup of control patients (n = 34), chosen for APACHE II scores that matched the patients with bloodstream infections, predicted and observed death rates were also similar (53.1 vs 52.9 percent). For patients with bloodstream infections, however, observed mortality (82.4 percent) significantly exceeded the predicted value (54.1 percent, p = 0.025). We conclude that critically ill patients who develop nosocomial bloodstream infections are at greater risk of death than patients with comparable severity of illness without this complication. The difference between the observed and predicted death rates, 28 percent, represents the excess mortality associated with bloodstream infection in critically ill patients.

Nosocomial infections in HIV-infected patients: preliminary results from a multicenter surveillance system (1989-1995).

OBJECTIVE: To describe the characteristics of and trends in nosocomial infection among human immunodeficiency virus (HIV)-infected patients. DESIGN: Multicenter prospective cohort study. SETTING/PATIENTS: HIV-infected patients were enrolled at time of first inpatient admission at five Veterans' Administration Medical Centers (VAMCs). RESULTS: As of March 1995, 2,541 patients with 6,625 inpatient admissions had been monitored in the five VAMCs. A total of 530 nosocomial infections were detected using standard Centers for Disease Control and Prevention definitions. Overall distribution by infection site was 31% for primary bloodstream infections (BSIs), 28% for urinary tract infections, 15% for pneumonia, and 26% for all other sites. Of BSIs, 63% were central line-associated bloodstream infections (CLABs). The rate of CLABs per 1,000 central line days was 6.5 (range, 2.3-8.3) for all patients from participating hospitals, similar to the median CLAB rate of 6.0 for patients in medical intensive-care units (ICUs) of National Nosocomial Infections Surveillance (NNIS) System hospitals from January 1990 through September 1994. For ICU-specific CLABs, the rate from hospitals reporting at least one ICU CLAB was 12.7 (range, 12.1-13.1), comparable to the 90th percentile of NNIS hospital medical ICUs (13.1). Staphylococcus aureus, associated with 35% of BSIs, was the most common nosocomial BSI pathogen. Our data demonstrated the following: 13 (10%) of 134 patients with CD4 counts > or = 200 cells/mm3 had a CLAB, compared with 61 (6%) of 1,011 patients with CD4 counts < 200 cells/mm3, P = .08; the per-day risk of CLABs did not change with increased duration of catheterization (P = .4); and the per-day risk of a temporary (ie, short-term) CLAB was greater than that of a permanent CLAB (P < .001). CONCLUSIONS: The data suggest that HIV-infected patients were at higher risk of acquiring a BSI than were patients in the NNIS population; patients with CD4 counts > or = 200 cell/mm3 and temporary central lines were at increased risk for BSI, perhaps reflecting widespread prophylaxis with trimethoprim-sulfamethoxazole among patients with CD4 counts < 200 cells/mm3, and, in contrast to most studies, S aureus, not coagulase-negative Staphylococcus, was the most common BSI pathogen.

Cardiac valve replacement in patients infected with the human immunodeficiency virus.

Major surgical procedures, especially when performed under general anesthesia, can depress immunological parameters measured in vitro. Therefore concern has been expressed that operation might have an adverse effect on the immune status of individuals infected with the human immunodeficiency virus (HIV). Four HIV-positive patients without symptoms of HIV disease underwent cardiac valve replacement in consequence of infective endocarditis. After up to 15 months postoperatively, 3 patients are alive and well without signs of progressive immunodeficiency or recurrent endocarditis. One patient died of recurrent endocarditis without evidence of HIV-related disease on autopsy. Cardiac operation does not seem to accelerate HIV-related immunodeficiency.

A city-wide outbreak of a multiple-drug-resistant strain of Mycobacterium tuberculosis in New York.

SETTING: Incident patients with active tuberculosis (TB) resistant to two or more drugs in New York City hospitals in 1992. OBJECTIVE: To examine the New York-wide distribution of Public Health Research Institute (PHRI) strain W of Mycobacterium tuberculosis, an extremely drug-resistant strain identified by a 17-band Southern hybridization pattern using IS6110, during the peak tuberculosis year of 1992. We also compared strain W with other strains frequently observed in New York. DESIGN: Blinded retrospective study of stored M. tuberculosis cultures by restriction fragment length polymorphism (RFLP) DNA fingerprinting, and chart review. RESULTS: We found 112 cultures with the strain W fingerprint and 8 variants in 21 hospitals among incident patients hospitalized in 1992. Almost all isolates were resistant to four first-line drugs and kanamycin. This single strain made up at least 22% of New York City multiple-drug-resistant (MDR) TB in 1992, far more than any other strain. Almost all W-strain cases were acquired immune deficiency syndrome (AIDS) patients. The cluster is the most drug-resistant cluster identified in New York and the largest IS6110 fingerprint cluster identified anywhere to date. CONCLUSION: Because recommended four-drug therapy will not sterilise this very resistant strain, there was a city-wide nosocomial outbreak of W-strain TB in the early 1990s among New York AIDS patients. Other frequently seen strains were either also very resistant, or, surprisingly, pansusceptible. Individual MDR strains can be spread widely in situations where AIDS and TB are both common.

Pseudomonas cepacia endocarditis and ecthyma gangrenosum.

A case of right-sided Pseudomonas cepacia endocarditis in a heroin addict is presented in which septic cutaneous vasculitis (ecthyma gangrenosum) is a prominent feature. Ecthyma gangrenosum, most commonly associated with sepsis due to P aeruginosa, has not been previously described with P cepacia septicemia.

Abnormal serum porphyrin levels in patients with the acquired immunodeficiency syndrome with or without hepatitis C virus infection.

OBJECTIVE: To define the contributions of human immunodeficiency virus (HIV) and hepatitis C virus infections to the development of porphyria cutanea tarda. DESIGN: Analysis of serum porphyrin levels in a cohort of 167 subjects. Serum samples were divided into 4 groups corresponding to the status of HIV and hepatitis C virus infections: positive-positive, positive-negative, negative-positive, and negative-negative. SETTING: Serum samples positive for HIV were obtained from the serum bank of an acquired immunodeficiency syndrome-HIV research center, and HIV-negative samples were obtained from a regional blood center. MAIN OUTCOME MEASURES: Spectrofluorometric measurement of serum porphyrin levels. RESULTS: The median values of porphyrin were 2.31 nmol/L (interquartile range [difference between the 25th and 75th percentiles]: 4.55) in the positive-positive group, 1.99 nmol/L (interquartile range: 1.63) in the positive-negative group, 1.31 nmol/L (interquartile range: 1.58) in the negative-positive group, and 1.14 nmol/L (interquartile range: 0.92) in the negative-negative group. The fluorescence emission spectra of samples with elevated porphyrin levels were identical with that reported for porphyria cutanea tarda. Elevated porphyrin levels were significantly associated with HIV infection (P < .001) and were observed in patients with an elevated level of alanine aminotransferase (P = .03). Infection with hepatitis C virus was also associated with an elevation in porphyrin levels, although the increase was not statistically significant (P = .16). Porphyrin levels in patients positive for HIV were not correlated with serum urea nitrogen or creatinine levels. None of the patients had symptomatic porphyria cutanea tarda. CONCLUSIONS: Factors associated with increased serum porphyrin levels included HIV infection, elevated alanine aminotransferase levels, and, to a lesser extent, hepatitis C virus infection. These findings suggest that patients with the above risk factors are potentially predisposed to the development of symptomatic porphyria cutanea tarda on further exposure to hepatotoxic agents.

Bacterial infections.

Non-opportunistic bacterial infections are an important cause of morbidity and mortality for HIV-infected adults and children. Factors associated with increased risk of these include altered B- and T-cell function; altered phagocytic cell function; skin and mucous membrane defects; and use of indwelling vascular catheters, antibiotics, or cytotoxic agents. The pathogens encountered most frequently are S. aureus, S. pneumoniae, H. influenzae, Salmonella sp., and Pseudomonas aeruginosa. Less commonly encountered organisms include Rhodococcus equi, Listeria monocytogenes, Shigella sp., and Nocardia asteroides, Strategies for prevention as well as diagnosis and treatment of these are discussed.

Ethical aspects in the care of patients with AIDS.

Over 91,000 cases of AIDS have been reported in United States, and it has been estimated that more than 1 million individuals are currently infected by the human immunodeficiency virus (HIV). The disease is growing most rapidly among intravenous drug abusers and minority patients. This accentuates some medical and ethical problems. Chief among these are the availability of competent care for patients and the willingness of physicians to treat these patients, issues related to HIV testing and counseling, patients' rights regarding the extent of treatment that should be given and access to and participation in clinical trials.