Effect of HIV on liver fibrosis among HCV-infected African Americans.

Degree of liver fibrosis largely determines treatment urgency for hepatitis C virus (HCV). This retrospective study examined fibrosis stages and predictive factors in African Americans with HCV monoinfection and human immunodeficiency virus (HIV)/HCV coinfection. Nearly 50% of patients had early-stage fibrosis in the study, despite the long duration of infection in many patients. HIV was associated with the early fibrosis group. These results indicate that a large proportion of patients with HCV infection, including those with HIV, could possibly await more-effective and better-tolerated treatment.

Review article: adherence to medication for chronic hepatitis C - building on the model of human immunodeficiency virus antiretroviral adherence research.

BACKGROUND: Treatment of hepatitis C virus (HCV) infection with pegylated interferon/ribavirin achieves sustained virological response in up to 56% of HCV mono-infected patients and 40% of HCV/human immunodeficiency virus (HIV)-co-infected patients. The relationship of patient adherence to outcome warrants study. AIM: To review comprehensively research on patient-missed doses to HCV treatment and discuss applicable research from adherence to HIV antiretroviral therapy. METHODS: Publications were identified by PubMed searches using the keywords: adherence, compliance, hepatitis C virus, interferon and ribavirin. RESULTS: The term 'non-adherence' differs in how it is used in the HCV from the HIV literature. In HCV, 'non-adherence' refers primarily to dose reductions by the clinician and early treatment discontinuation. In contrast, in HIV, 'non-adherence' refers primarily to patient-missed doses. Few data have been published on the rates of missed dose adherence to pegylated interferon/ribavirin and its relationship to virological response. CONCLUSIONS: As HCV treatment becomes more complex with new classes of agents, adherence will be increasingly important to treatment success as resistance mutations may develop with suboptimal dosing of HCV enzyme inhibitors. HIV adherence research can be applied to that on HCV to establish accurate methods to assess adherence, investigate determinants of non-adherence and develop strategies to optimize adherence.

Hepatitis C patients' self-reported adherence to treatment with pegylated interferon and ribavirin.

BACKGROUND: Prior research on adherence to hepatitis C treatment has documented rates of dose reductions and early treatment discontinuation, but little is known about patients' dose-taking adherence. AIMS: To assess the prevalence of missed doses of pegylated interferon and ribavirin and examine the correlates of dose-taking adherence in clinic settings. METHODS: One hundred and eighty patients on treatment for hepatitis C (23% coinfected with HIV) completed a cross-sectional survey at the site of their hepatitis C care. RESULTS: Seven per cent of patients reported missing at least one injection of pegylated interferon in the last 4 weeks and 21% reported missing at least one dose of ribavirin in the last 7 days. Dose-taking adherence was not associated with HCV viral load. CONCLUSIONS: Self-reported dose non-adherence to hepatitis C treatment occurs frequently. Further studies of dose non-adherence (assessed by method other than self-report) and its relationship to HCV virological outcome are warranted.

Thyrotoxicosis outbreak linked to consumption of minced beef and chorizo: Minas, Uruguay, 2003-2004.

OBJECTIVES: Thyrotoxicosis is produced by excessive quantities of thyroid hormone. Its most common causes involve inflammation of the thyroid gland. Much more rarely, thyrotoxicosis is due to exogenous intake of thyroid hormones or iodide compounds. Few outbreaks are documented. In 2003 to early 2004, doctors in Minas, Uruguay noted a sharp increase in the incidence of thyrotoxicosis in a neighbourhood, with multiple cases within families. The objective of this study was to identify the source of the outbreak. STUDY DESIGN: A case-control study was conducted following surveillance and environmental inspection. METHODS: Case patients were symptomatic residents of Minas with documented thyroid-stimulating hormone concentrations <0.1 microUI/ml or <0.49 microUI/ml and elevated free triiodothyronine or free thyroxine. Control subjects were frequency matched with case patients by barrio of residence and age. Case patients, control subjects and persons who prepared and purchased household food were interviewed using a standard questionnaire. Odds ratios adjusted (AOR) for age and gender were calculated by logistic regression in SUDAAN to account for neighbourhood and family clustering. RESULTS: Fifty-nine case patients aged 9-74 years (median 39 years) were identified. Of the 56 interviewed, 52% were women and 71% resided in one barrio. Case patients were more likely than control subjects to eat minced beef at least weekly and purchase it from Butcher A [AOR 6.1; 95% confidence interval (CI) 2.61-14.46], and were more likely to eat chorizo at least weekly and purchase it from Butcher B (AOR 11.6; 95% CI 1.30-102.27). One beef supplier selling meat cuts containing thyroid gland was identified. CONCLUSIONS: The most likely cause of this outbreak of thyrotoxicosis was consumption of minced beef and chorizo contaminated with thyroid gland. Tight regulation and oversight of slaughter, processing, and sales of meat and meat products are imperative for prevention of future outbreaks.

Effects of pregnancy on CYP3A and P-glycoprotein activities as measured by disposition of midazolam and digoxin: a University of Washington specialized center of research study.

The objectives of the study were to evaluate the effects of pregnancy on CYP3A and P-glycoprotein (P-gp) activities, as measured by disposition of midazolam and digoxin, respectively. Thirteen women received digoxin (0.25 mg p.o.) and midazolam (2 mg p.o.) in random order, separated by 1-2 weeks at 28-32 weeks gestation, and the same order was repeated at 6-10 weeks postpartum. Plasma and urine concentrations were determined by liquid chromatography-mass spectrometry and analyzed by noncompartmental methods. Midazolam CL/F(unbound) (593 +/- 237 l/min vs. 345 +/- 103 l/min; P = 0.007), digoxin CL(Renal, unbound) (272 +/- 45 ml/min vs. 183 +/- 37 ml/min; P < 0.002) and digoxin CL(secretion,) (unbound) (109 +/- 34 ml/min vs. 58 +/- 22 ml/min; P < 0.002) were higher during pregnancy than postpartum. These data are consistent with increased hepatic and/or intestinal CYP3A and renal P-gp activities during pregnancy.

"Titicut follow-up": successful transfer of assaultive patients from a high security facility to a less restrictive setting.

Currently many state mental health agencies are redoubling their efforts to close or downsize state hospitals and place their populations in less restrictive settings. Prior to 1990, certain assaultive non-criminal male patients from public facilities operated by the Massachusetts Department of Mental Health (DMH) could be transferred to prison psychiatric facilities operated by the Department of Corrections (DOC). In 1989 that practice was declared illegal, and clients so placed were ordered returned to DMH facilities. This case study describes the liaison process by which patients remaining in the DOC facility returned to DMH facilities, describes their subsequent hospital course, and reviews the validity of policy assumptions made about these patients' needs in the context of this follow-up data. The results of this analysis indicate that many fewer patients in this group of primarily chronic schizophrenic men required a secure facility upon their return than was previously assumed.

The importance of neurobiological research to the prevention of psychopathology.

There is both a biological and environmental component to the neural substrates for various forms of psychopathology. Brain dysfunction itself not only constitutes a formidable liability to psychopathology, but also has an impact on environmental and social responses to the individual, compounding the risk for an adverse outcome. Environmental conditions, such as social and physical stimulus deprivation, poverty, traumatic stress, and prenatal drug exposure, can further compromise brain function in the context of existing liabilities. The relationship between genetic and environmental processes is interactive, fluid, and cumulative in their ability to influence an individual's developmental trajectory and alter subsequent behavioral outcomes. Given the codependent relationship between these processes, brain function is now believed to be malleable via manipulations of the environment in ways that may decrease liability for psychopathology. Research that explores these relationships and ways in which interventions can redirect this developmental track may substantially advance both the science and practice of prevention. Studies attempting to isolate the neurobiological effects of socioenvironmental factors are reviewed, implications for intervention strategies are discussed, and a future research agenda is proposed to provide greater insight into specific brain-environment relationships. Armed with this knowledge, prevention scientists may eventually design programs that directly target these effects to reverse or attenuate negative outcomes.

The clinical significance of flow cytometry crossmatching in heart transplantation.

BACKGROUND: Flow cytometry crossmatching is more sensitive than cytotoxic methods in identifying preformed antibodies to donor alloantigens. However, the significance of a positive flow crossmatch remains unknown for a recipient of a heart transplant who has a negative anti-human globulin crossmatch. METHODS: Flow crossmatching was performed retrospectively for 92 recipients of a primary cardiac allograft who underwent transplantation with a negative AHG crossmatch. RESULTS: Forty-six patients were flow crossmatch-positive for alloantibody: 20 were positive on both T and B lymphocytes, 12 were positive only on B lymphocytes, and 13 were positive only on T lymphocytes. Eleven had autoantibody invalidating the flow crossmatch with donor cells. Thirty-six patients had negative flow crossmatch. A significantly higher incidence of graft dysfunction with vascular rejection by 6 months was found for patients who had a positive flow crossmatch on B lymphocytes. This group also had an increased incidence of mortality within this same period. Patients who were flow crossmatch-positive on T and B lymphocytes were more likely to experience greater than two episodes of treated cellular rejection within the first 6 months. Flow crossmatch-positive patients stayed longer in the hospital in comparison to the other two groups, although the increases were not statistically significant. There were no differences between groups with regard to time to first rejection, absence of rejection episodes, episodes of decreased cardiac index (<2.3 L/m2), depressed left and right ventricular ejection fraction, or development of transplant atherosclerosis. CONCLUSION: A positive flow crossmatch identified a subset of patients who are predisposed to development of vascular rejection or are more likely to have frequent cellular rejection.

Heart transplant rejection with hemodynamic compromise: a multiinstitutional study of the role of endomyocardial cellular infiltrate. Cardiac Transplant Research Database.

BACKGROUND: The natural history of patients experiencing hemodynamic compromise with rejection has been incompletely characterized. This multiinstitutional study examined the outcome of such episodes, particularly with regard to the extent of cellular infiltrate on the index endomyocardial biopsy. METHODS: From January 1, 1990, through June 30, 1994, 3367 patients in the Cardiac Transplant Research Database experienced 4137 episodes of rejection. Severe hemodynamic compromise occurred in approximately 5% of the rejection episodes, and this proportion remained relatively constant over time. RESULTS: Recipient risk factors for rejection with severe hemodynamic compromise included black race, female recipient sex, and diabetes. The 3-month actuarial survival rate was 60% after rejection with severe hemodynamic compromise versus 95% after rejection with no or mild compromise. Low initial biopsy score conferred a higher early survival, but a lower survival at 2 years after rejection with severe hemodynamic compromise. Among patients who survive an initial rejection episode with severe hemodynamic compromise, survival at 2 years after an episode was 46% among those who had a low initial biopsy score versus 84% with a high biopsy score. CONCLUSIONS: Rejection with hemodynamic compromise, although rare, represents a major complication of heart transplantation with a poor long-term outcome. Survivors of hemodynamically compromising rejection episodes associated with low biopsy scores in the International Society for Heart and Lung Transplantation grading system have a significantly worse long-term outcome than survivors of episodes associated with high scores. These findings suggest that immunologic mechanisms other than lymphocytic infiltration of the cardiac allograft are important and distinct causes of allograft dysfunction.

Who gets a heart? Rationing and rationalizing in heart transplantation.

National policy on organ transplantation is made by the United Network for Organ Sharing (UNOS), a representative body composed of health care professionals and patients. Standardized criteria for determining when a patient should be placed on the waiting list for heart transplantation are now in effect nationwide. Current and future directions to maximize the utilization of available donated organs are explored.

Treatment of hyperlipidemia after heart transplantation and rationale for the Heart Transplant Lipid Registry.

Hyperlipidemia occurs frequently after heart transplantation, and accelerated coronary artery disease remains the major cause of morbidity and mortality in patients who survive more than 1 year after heart transplantation. However, the risks and benefits of lipid-lowering therapy after heart transplantation remain poorly defined, and national guidelines for lipid-lowering drug therapy do not specifically address treatment of dyslipidemia in transplant recipients. Since the initial reports in the 1980s of rhabdomyolysis in heart transplant patients receiving high-dosage lovastatin, results of 11 post-transplantation series that used lovastatin, simvastatin, or pravastatin at lower dosages as drug monotherapy have been published. These studies have shown an overall 1% incidence of rhabdomyolysis, defined as creatine kinase > 10 times the upper limit of normal plus muscle symptoms. One randomized, controlled prospective trial has investigated the effects of lipid-lowering pharmacotherapy on patient outcome in cardiac transplant recipients. At 1-year follow-up in this nonblinded, single-center trial, patients treated with pravastatin (20 or 40 mg/day) initiated within 2 weeks of transplantation had a significant reduction in mortality rate and a significantly lower incidence of transplant arteriopathy. A number of important issues remain unanswered regarding treatment guidelines in patients with hyperlipidemia after heart transplantation. In January 1995 we began the Heart Transplant Lipid Registry, with 12 participant centers, to gather data prospectively on the efficacy and safety of lipid-lowering drugs in the treatment of dyslipidemia after heart transplantation.

Female PCP-using jail detainees: proneness to violence and gender differences.

Previous studies indicate that PCP users have different characteristics from other drug users and that female PCP use is more common than use among males. Furthermore, there is evidence that those who respond to PCP with violence may differ from those who do not. This study attempted to examine comprehensively the psychological, behavioral, and background factors among female jail inmates that may contribute to a PCP preference and subjects' perception of various behavioral states while using PCP. Female PCP users were further examined relative to male PCP users to differentiate them on the basis of these perceptual factors. A distinction was further made between females and males prone to PCP-induced violence and those who do not become violent with respect to the above psychological and behavioral measures. Our results showed differences between male and female PCP users that are discrepant with the assumption that men and women perceive similar drug-related experiences. In particular, female PCP using subjects reported more dysphoria and aggressiveness when not using PCP, while male subjects were more likely to report aggressive behavior and dysphoria under the influence. Overall, these results suggest that males who prefer PCP may be self-stimulating and females who prefer PCP may be attempting to self-medicate.

Seroepidemiology of infections due to spotted fever group rickettsiae and Ehrlichia species in military personnel exposed in areas of the United States where such infections are endemic.

A prospective, seroepidemiologic study of spotted fever group rickettsiae (SFGR) and Ehrlichia infections was done among 1194 US military personnel exposed in a heavily tick-infested area of Arkansas in 1990. Seroconversion (4-fold) and seroprevalence rates were determined by indirect immunofluorescent antibody assays. Seroconversions to SFGR occurred in 30 persons (2.5%), whereas seroconversion to Ehrlichia species occurred in 15 (1.3%). The majority of seroconverters did not report symptoms (22/30 [73%] of SFGR seroconverters; 10/15 [67%] of Ehrlichia species seroconverters). History of tick attachment was associated with seroconversion to SFGR (relative risk [RR] = 4.3, P < .001) and Ehrlichia species (RR = 3.6, P < .05). Use of permethrin-impregnated uniforms significantly decreased risk of infection (P < .01); use of bed nets increased risk by 4-fold. Tickborne infections represent a significant threat to military personnel training in areas in which these infections are endemic.

National surveillance for Rocky Mountain spotted fever, 1981-1992: epidemiologic summary and evaluation of risk factors for fatal outcome.

Between 1981 and 1992, the Centers for Disease Control collected and summarized 9,223 cases of Rocky Mountain spotted fever (RMSF) reported from 46 states. Four states (North Carolina, Oklahoma, Tennessee, and South Carolina) accounted for 48% of the reports. The annual incidence per million U.S. population decreased from a high in 1981 of 5.2 to a low in 1992 of 2.0, primarily due to decreased incidence in the southeast. Case report forms were filed on 7,650 patients, of whom 4,217 had laboratory-confirmed RMSF. The age group with the highest incidence was those 5-9 years of age. Most cases (90.0%) occurred between April 1 and September 30 and included a history of tick attachment (59.6%). Reported symptoms included fever (94.0%), headache (86.2%), myalgia (82.5%), and rash (80.2%). The case-fatality ratio was 4.0%. Risk factors associated with death included older age, delay in treatment or no treatment, and treatment with chloramphenicol (compared with tetracycline); however, insufficient data existed to fully assess the confounding effect of severity of illness on antibiotic choice.

Psychological correlates of frequency and type of drug use among jail inmates.

The comorbidity of drug abuse and various forms of psychopathology is pervasive and well documented. In particular, the incidence of depression, anxiety, and antisocial personality disorder is high among substance abusers relative to non-drug abusers. Offender populations have a high rate of substance abuse, and some studies suggest that the incidence of psychopathology may be even greater than in other drug using groups. In order to identify specific types of psychopathology as they relate to drug preferences and frequency of use among drug-using offenders, arrestees at the Baltimore City Detention Center were examined. During extensive interviews, drug-abusing arrestees provided information pertaining to their backgrounds, childhood histories, biological relatives, present behaviors, and criminal and drug histories. Additionally, several psychological inventories were administered to evaluate the presence of depression, anxiety, psychopathy, and impulsivity. Results indicate that the frequency with which subjects reported using specific drugs and drug of choice were significantly associated with particular measures of psychopathology. A composite measure of psychopathy was especially related to the frequency of alcohol, marijuana, and cocaine use. Subjects who reported using cocaine on a frequent basis scored high on measures of hostility and reported committing more property crimes, while violent crimes were more likely to be reported by subjects scoring high on the measure of psychopathy. Other noteworthy findings will be discussed along with the limitations of this study.

Immunogenicity of rabies vaccines used during an urban epizootic of rabies in Mexico.

From 1 July 1987 to 31 December 1988, 30% of 247 rabid dogs in Hermosillo, Mexico had a positive history of rabies vaccination. Serosurveys suggested that inactivated suckling mouse brain vaccine (INACT-SMBV) and inactivated tissue culture vaccine (INACT-TC) used before and during the epizootic were poor immunogens. Prospective studies showed that only about one-third of dogs vaccinated with INACT-SMBV were seropositive 5 weeks after vaccination. Lack of vaccine potency was the most likely cause of poor immunogenicity. Rabies vaccines should be evaluated periodically by measuring antibody responses in animals. In some circumstances, minimum seroconversion rates and antibody titres in vaccinated animals may be better measures of immunogenicity than relative potency.

Evaluation of specificity of indirect enzyme-linked immunosorbent assay for diagnosis of human Q fever.

Ninety-five acute- and convalescent-phase serum specimens from 48 patients suspected of having rickettsial or Legionella infections were assayed for antibodies to Coxiella burnetii, the causative agent of Q fever. To evaluate the specificity of the indirect enzyme-linked immunosorbent assay (ELISA) for human Q fever, we compared the ELISA results with those of the indirect immunofluorescence antibody (IFA) test. The ELISA data were analyzed by two different criteria for a positive test. The first criterion for positive results by ELISA was based upon diagnostic titers established in a study of 150 subjects who had no demonstrable cellular or humoral immune responses to C. burnetii phase I or phase II whole cells or phase I lipopolysaccharide. The second criterion was based upon diagnostic antibody titers in a study of 51 subjects who had been diagnosed as having clinical Q fever and had fourfold or greater rises in humoral immune responses to C. burnetii phase I and phase II whole-cell antigens. A comparison of the ELISA and IFA test results of the 95 serum specimens indicated excellent agreement between the tests (Kappa = 92.9%; P < 0.05). None of the 38 patients whose etiologies were confirmed serologically as Legionnaires' disease or rickettsial diseases other than Q fever were classified as positive for C. burnetii by the ELISA. Only one patient identified by the IFA test as having Q fever was not scored positive by the ELISA. These results suggest that the ELISA is useful for epidemiologic screening and as a diagnostic test for human Q fever.