Increased density of neurons containing NADPH diaphorase and nitric oxide synthase in the cerebral cortex of patients with HIV-1 infection and drug abuse

To determine whether nitrogen monoxide (nitric oxide; NO) synthase (NOS) and NADPH diaphorase (NDP) co-containing cerebrocortical neurons (NOSN) neurons are affected in patients infected with human immunodeficiency virus type 1 (HIV-1) with and without associated intake of drugs of abuse, we examined the temporal neocortex of 24 individuals: 12 HIV-1 positive (including 3 drug users, 9 non-drug users) and 12 HIV-1 negative (including 6 drug users, and 6 non-drug users). Histochemical labeling for NDP-an enzymatic domain co-expressed in the NOS enzyme-was employed to visualize NOSN. Drug abuse and HIV-1 infection cause independently an increase in NOSN density, but combined they result in up to a 38-fold increase in NOSN density, suggesting that the combination of these factors induces NOS expression powerfully in neurons that normally do not synthesize NDP/NOS. This is associated with an increase in the proportion of NOSN displaying dystrophic changes, indicating that NOSN undergo massive degeneration in association with NOS synthesis induction. The increase in density of NOSN in HIV-1 infected drug abusers may be among the important sources of NO mediating cerebrocortical dysfunction, and the degeneration of NOS-containing local circuit neurons in patients with HIV-1 infection or drug abuse may underlie in part their neuropsychiatric manifestations.     

Compliance with isoniazid prophylaxis in jail

The incidence of tuberculosis in New York City has risen dramatically in the last decade, an increase that has also been seen in the incarcerated population on Rikers Island, New York City's principal jail. We have investigated the establishment and maintenance of compliance with isoniazid prophylaxis in this population. Factors affecting compliance were studied in a sample of young men who were found to be tubercullin-reactive at the time of their incarceration. Compliance was quantified by determining the number of doses taken divided by the total number of available doses. Mean compliance for the 74 subjects was 37.5%. Two factors were important determinants of compliance: (1) the building where the inmate was incarcerated and (2) his knowledge of tuberculoses and the isoniazed regimen. The influence of the housing unit on compliance suggests that administrative responses to prison overcrowding, an increasingly prevalent condition in the nation's jails and prisons, may have an unintended and detrimental effect on medical care and public health.     

Rates and Predictors of Uncontrolled Hypertension Among Hypertensive Homeless Adults Using New York City Shelter-Based Clinics

PURPOSE

We undertook a study to determine the rates, predictors, and barriers to blood pressure control among homeless and nonhomeless hypertensive adult patients from 10 New York City shelter-based clinics.

METHODS

The study was a retrospective chart review of blood pressure measurements, sociodemographic characteristics, and factors associated with homelessness and hypertension extracted from the medical records of a random sample of hypertensive patients (N = 210) in 2014.

RESULTS

Most patients were African American or Hispanic; 24.8% were female, and 84.3% were homeless for a mean duration of 3.07 years (SD = 5.04 years). Homeless adult patients were younger, had less insurance, and were more likely to be a current smoker and alcohol abuser. Of the 210 hypertensive patients, 40.1% of homeless and 33.3% of nonhomeless patients had uncontrolled blood pressure (P = .29) when compared with US rates for hypertensive adults, which range between 19.6% and 24.8%, respectively; 15.8% of homeless patients had stage 2 hypertension (P = .27). Homeless hypertensive patients with diabetes or multiple chronic diseases had better blood pressure control (P <.01). In logistic regression, lack of insurance was associated with inadequate blood pressure control (P <.05).

CONCLUSIONS

The high rate of uncontrolled hypertension among hypertensive homeless adults is alarming. We propose comprehensive approaches to improve social support, access to medical insurance, and medication adherence, the lack of which complicate blood pressure control, targeted health education, and life style modifications using mobile health strategies for this mobile population.     

Positive predictors for gastroesophageal reflux disease and the therapeutic response to proton-pump inhibitors

AIM:To identify objective and subjective predictors for the reliable diagnosis of gastroesophageal reflux disease(GERD)and the response to proton pump inhibitor(PPI)therapy.METHODS:Retrospectively,683 consecutive patients suspected for GERD who underwent pH-metry/impedance measurement(pH/MII)were analyzed.All patients had previously undergone standard PPI treatment(e.g.,pantoprazole 40 mg/d or comparable).Four hundred sixty patients were at least 10 d off PPIs(group A),whereas 223 patients were analyzed during their ongoing PPI therapy(group B).In addition,all patients completed a standardized symptom-and lifestyle-based questionnaire,including the therapeutic response to previous PPI trials on a 10-point scale.Uniand multivariance analyses were performed to identify criteria associated with positive therapeutic response to PPIs.RESULTS:In group A,positive predictors(PPs)for response in empirical PPI trials were typical GERD symptoms(heartburn and regurgitation),a positive symptom index(SI)and pathological results in pH/MII,along with atypical symptoms,including hoarseness and fullness.In group B,regular alcohol consumption was associated with the therapeutic response.The PPs for pathological results in pH/MII in group A included positive SI,male gender,obesity,heartburn and regurgitation.In group B,the PPs were positive SI and vomiting.Analyzing for positive SI,the PPs were pathological pH and/or MII,heartburn regurgitation,fullness,nausea and vomiting in group A and pathological pH and/or MII in group B.CONCLUSION:Anamnestic parameters(gender,obesity,alcohol)can predict PPI responses.In non-obese,female patients with non-typical reflux symptoms,pH/MII should be considered instead of empirical PPIs.     

Clinical manifestations and predictors of disease progression in drug users with human immunodeficiency virus infection.

BACKGROUND AND METHODS. To examine the clinical course of human immunodeficiency virus (HIV) infection in injection-drug users, we conducted a prospective study of a cohort of patients in a methadone-treatment program in New York City from July 1985 through December 1990. The patients underwent standardized evaluations at base line and semiannually thereafter and received on-site primary medical care. Rates of progression to the acquired immunodeficiency syndrome (AIDS) and major outcomes before the development of AIDS were examined by univariate analyses; the risk of AIDS was also assessed by product-limit survival analysis and proportional-hazards regression. RESULTS. Of 318 HIV-seropositive patients who did not yet have AIDS (171 men and 147 women), 90 were black, 179 were Hispanic, and 49 were white; the median age was 33 years. Over a median of 3.0 years of follow-up, 55 (17 percent) received a diagnosis of AIDS (incidence per 100 person-years, 5.8). Major outcomes before the development of AIDS included oral candidiasis (incidence per 100 person-years, 11.2), pyogenic bacterial infections including pneumonia and sepsis (8.0), pulmonary tuberculosis (1.2), multiple constitutional symptoms (13.6), and herpes zoster (1.3). There were 41 deaths from AIDS, and 13 seropositive patients without AIDS (4.1 percent) died of bacterial infections, as compared with only 1 of 411 seronegative patients studied (P < 0.001). The incidence of AIDS was 62 percent lower among those who took zidovudine than among those who did not (P = 0.02). In the multivariate analysis, progression to AIDS was best predicted by low numbers and percentages of CD4+ lymphocytes, nonuse of zidovudine, and the presence of oral candidiasis, bacterial infections, or tuberculosis. There was no consistent relation between progression to disease and the continued use of injection drugs. CONCLUSIONS. HIV-infected injection-drug users have progression to AIDS at rates comparable to those of other HIV-infected groups, but they have substantial pre-AIDS morbidity and mortality, particularly from bacterial infections, which also appear to predict disease progression.     

The contribution of recently acquired Mycobacterium tuberculosis infection to the New York City tuberculosis epidemic, 1989-1993

Current theory in the molecular epidemiology of tuberculosis holds that tuberculosis cases harboring Mycobacterium tuberculosis strains with a common deoxyribonucleic acid (DNA) fingerprint are the result of recent M. tuberculosis transmission. Here we propose a mathematical approach independent of DNA fingerprinting to estimating the percentage of recent transmissions responsible for current tuberculosis incidence. The "short-term reproductive number" of tuberculosis is defined as the average number of tuberculosis cases developing within 1 year of infection. Multiplying the short-term reproductive number by the number of tuberculosis cases in each year and dividing by the subsequent year's tuberculosis case burden equals the proportion of tuberculosis cases in the subsequent year that are due to recent transmission. We carried out separate calculations for human immunodeficiency virus (HIV)-negative and HIV-positive tuberculosis cases. We applied the model to pulmonary (infectious) tuberculosis cases diagnosed in New York City during 1989-1993, using tuberculosis and AIDS surveillance data. Model-based estimates of the proportion of tuberculosis due to recent transmission were lower than estimates based on DNA fingerprints. Reconciliation of these divergent estimates may require the re-estimation of model parameters from data collected de novo, additional model development, and further advances in DNA fingerprinting methods.     

Detection of antibody to Mycobacterium tuberculosis protein antigens in the cerebrospinal fluid of patients with tuberculous meningitis

Antibodies against Mycobacterium tuberculosis antigens were detected by enzyme-linked immunosorbent assay in cerebrospinal fluid (CSF) samples obtained from 442 patients with tuberculous meningitis (TBM) and 102 control patients. Antibodies were found in the CSF of 87% of patients with clinical (culture-negative) TBM, 72% of patients with culture-positive TBM, and 65% of patients with autopsy-proven TBM. That anti-M. tuberculosis antibodies were detected in the CSF of patients with clinically diagnosed cases more frequently than in patients with culture-positive cases suggests that the detection of antibodies in CSF tends to decrease as bacillary load increases. Of the patients with clinical TBM who were coinfected with human immunodeficiency virus (HIV), 70% exhibited anti-M. tuberculosis antibody in CSF, which suggests that antibody responses in this group were substantially weaker than those in HIV-negative patients with clinical TBM. Some groups showed a stronger response to certain antigens, which suggests that antigen recognition patterns may be specific for the stage of disease.     

High risk of active tuberculosis in HIV-infected drug users with cutaneous anergy.

OBJECTIVES--To determine the incidence of active tuberculosis in human immunodeficiency virus (HIV)-seropositive and HIV-seronegative drug injectors with cutaneous anergy and to examine the effectiveness of isoniazid chemoprophylaxis in preventing tuberculosis among drug injectors with positive tuberculin test results. DESIGN AND SETTING--Prospective observational study linked to an ongoing study of HIV infection within a New York City (NY) methadone program; subjects also underwent routine intradermal tuberculin testing and multiple-antigen delayed-type hypersensitivity skin testing. The 31-month study period ended December 31, 1990. METHODS--Anergic subjects and tuberculin reactors who were HIV seropositive were compared by HIV disease status and CD4+ T-lymphocyte levels. Tuberculosis incidence was calculated for anergics (none treated with isoniazid) and for treated and untreated tuberculin reactors, by HIV serological status. RESULTS--Among those seropositive for HIV, anergic subjects had more advanced HIV disease and fewer CD4+ cells (median 0.33 vs 0.56 x 10(9)/L, P less than .01) compared with tuberculin reactors, although neither clinical status nor CD4+ cell counts consistently predicted anergy. Five (7.6%) of 68 anergic subjects who were HIV seropositive and none of 52 anergic subjects who were HIV seronegative (n = 18) or of unknown (n = 34) HIV serological status developed active tuberculosis during the study period (P less than .05). The tuberculosis incidence rate among anergic subjects who were HIV seropositive was 6.6 cases per 100 person-years (95% confidence interval [Cl], 2.1 to 15.3). Of 25 HIV-seropositive tuberculin reactors who did not receive or complete 12 months of isoniazid prophylaxis, tuberculosis incidence was 9.7 cases per 100 person-years (95% Cl, 2.6 to 24.7; P = 0.56, compared with the rate among anergic HIV seropositives); there were no cases of tuberculosis in 53.4 person-years of follow-up for 27 HIV-seropositive tuberculin reactors who received 12 months of prophylaxis (rate difference between treated and untreated groups, 9.7 cases per 100 person-years, 95% Cl, 1.3 to 18.0). CONCLUSION--Drug injectors with cutaneous anergy who are seropositive for HIV are at high risk of active tuberculosis, similar to that among untreated HIV-seropositive tuberculin reactors. A decreased incidence of active tuberculosis was seen in HIV-seropositive tuberculin reactors receiving 12 months of isoniazid chemoprophylaxis, compared with untreated or partially treated subjects. These results support the routine use of delayed-type hypersensitivity testing to accompany tuberculin testing for drug injectors with known or suspected HIV infection, and consideration of isoniazid prophylaxis for anergic as well as tuberculin-reactive subjects who are HIV seropositive, in populations with a high prevalence of coexisting HIV and Mycobacterium tuberculosis infection.     

Impact of Therapeutic Plasma Exchange on Hemodynamic Parameters in Medical Intensive Care Unit Patients: An Observational Study

Therapeutic plasma exchange (TPE) is an extracorporeal treatment with reported beneficial as well as detrimental effects on circulation. However, there is a lack of data using advanced hemodynamic monitoring during TPE. Therefore, we investigated the effects of TPE on hemodynamic parameters derived from transpulmonary thermodilution (TPTD) as well as the risk for transfusion‐related acute lung injury (TRALI). We compared hemodynamic parameters obtained before and after a total of 30 sessions of TPE treatment in 10 intensive care unit patients. Among standard hemodynamic parameters, heart rate (P < 0.012) and systolic blood pressure (P < 0.008) significantly increase, whereas neither mean arterial pressure nor diastolic blood pressure was altered after TPE. The TPTD‐derived cardiac function parameters, cardiac index (CI; P = 0.035), cardiac power index (CPI; P = 0.008), global ejection fraction (GEF; P = 0.002), and stroke volume index (SVI; P = 0.014), were significantly higher after TPE. Furthermore, systemic vascular index significantly increased (P < 0.042). Among the cardiac preload parameters, central venous pressure was significantly lower after TPE (P < 0.001), while the global end‐diastolic volume index (GEDVI) did not change. Contractility marker dPmax did not change. Finally, TPE application did not significantly alter the pulmonary hydration and permeability parameters, extravascular lung water index (EVLWI) and pulmonary vascular permeability index. Vasopressor dose was not statistically significantly altered. Considering increases in SVI, CI, GEF, and CPI and stable values for GEDVI, EVLWI, and dPmax, our data do not give any hint for hemodynamic impairment or TRALI.