Mercapturate metabolism of 4-hydroxy-2-nonenal in rat and human cerebrum

4-Hydroxy-2-nonenal (HNE), a potent toxin formed in the brain from oxidation of polyunsaturated fatty acids, is increased in Alzheimer disease (AD), where it is a proposed effector of amyloid beta peptide-mediated neurotoxicity. Detoxification of HNE via the mercapturic acid pathway (MAP) is the primary means by which other organs, such as liver, limit its toxic effects. Here we examined the distribution and activity of MAP detoxification for HNE in cerebrum. Our results showed that rat cerebral cortex and especially synaptosomes were less well equipped to detoxify HNE via the MAP than liver. Glutathione transferases (GSTs) catalyze the committed step in the MAP; GST-mu and GST-pi, but not OST-alpha, were detected in neurons and astrocytes in cerebrum from AD patients and controls. MAP activity in frontal cortex of AD patients was modestly but significantly increased compared to controls. These data suggest that lipid peroxidation may present a greater toxic burden to cerebrum than to other organs, and that a component of response to injury in late stage AD is a slight increase in MAP activity.     

Support for bereaved owners of pets

TOPIC: The bond that exists between people and their pets and its impact on physical and mental health. PURPOSE: To review the current literature and explore the clinical implications of bereavement related to pets. SOURCES: A comprehensive review of the bereavement, veterinarian, and agricultural literature related to attitudes and response patterns to pet and animal death. CONCLUSIONS: The death or loss of a beloved pet can be a life-changing event.     

The ecology of infectious disease: effects of host diversity and community composition on Lyme disease risk

The extent to which the biodiversity and community composition of ecosystems affect their functions is an issue that grows ever more compelling as human impacts on ecosystems increase. We present evidence that supports a novel function of vertebrate biodiversity, the buffering of human risk of exposure to Lyme-disease-bearing ticks. We tested the Dilution Effect model, which predicts that high species diversity in the community of tick hosts reduces vector infection prevalence by diluting the effects of the most competent disease reservoir, the ubiquitous white-footed mouse (Peromyscus leucopus). As habitats are degraded by fragmentation or other anthropogenic forces, some members of the host community disappear. Thus, species-poor communities tend to have mice, but few other hosts, whereas species-rich communities have mice, plus many other potential hosts. We demonstrate that the most common nonmouse hosts are relatively poor reservoirs for the Lyme spirochete and should reduce the prevalence of the disease by feeding, but rarely infecting, ticks. By accounting for nearly every host species' contribution to the number of larval ticks fed and infected, we show that as new host species are added to a depauperate community, the nymphal infection prevalence, a key risk factor, declines. We identify important "dilution hosts" (e.g., squirrels), characterized by high tick burdens, low reservoir competence, and high population density, as well as "rescue hosts" (e.g., shrews), which are capable of maintaining high disease risk when mouse density is low. Our study suggests that the preservation of vertebrate biodiversity and community composition can reduce the incidence of Lyme disease.     

Acute onset of neutrophilic dermatosis in patients after therapy with a COX-2-specific inhibitor

Case 1 A 31‐year‐old black woman with an 8‐year history of Crohn's disease (CD) presented with multiple, erythematous, tender, leg nodules. She had started to develop these areas approximately 2 weeks earlier. About 1 week prior to the development of these areas, the patient had gone to her primary care physician because of increasing joint pains. She was given rofecoxib, 50 mg/day. A few months earlier, the patient had stopped taking the medication that had been prescribed for CD: sulfasalazine and prednisone. Since stopping sulfasalazine and prednisone, her gastrointestinal symptoms had increased. After starting rofecoxib, the patient did not notice any significant change in her gastrointestinal symptoms, although her arthritic symptoms improved. Earlier on the day of presentation, the patient's gastroenterologist had instructed her to stop rofecoxib, and to re‐start sulfasalazine and prednisone. On physical examination, the patient had multiple erythematous nodules on both legs, predominantly on the lower legs anteriorly and posteriorly ( Fig. 1a ). Some of the nodules showed central pustules and some showed superficial epidermal ulceration ( Fig. 1b ). A biopsy was performed on an indurated lesion that had not yet ulcerated.

Figure 1 Open in figure viewer PowerPoint Multiple, erythematous nodules on the legs of a patient with Crohn's disease (Case 1). Biopsy specimens from some lesions showed subepidermal pustule formation with or without epidermal ulceration     

Adherence to CDC STD guideline recommendations for the treatment of Chlamydia trachomatis infection in two managed care organizations

BACKGROUND: The extent of adherence to the Centers for Disease Control and Prevention (CDC) STD guidelines by clinicians practicing in managed care settings is unknown.GOAL The goal was to assess adherence to the CDC guideline recommendations for the treatment of genital chlamydial infection, by clinicians at two group model managed care organizations. DESIGN: Retrospective cohort study of men and women with laboratory-confirmed chlamydial infection. Patients were members of either the Kaiser Permanente Foundation Health Plan of Colorado or HealthPartners of Minneapolis/St. Paul who had tested positive for cervical or urethral chlamydial infection during the period from January 1, 1998, through June 30, 1999. RESULTS: During the study period, 1,078 patients with positive tests for genital Chlamydia trachomatis were identified. More than 97% of men and nonpregnant women and more than 98% of pregnant women were prescribed treatment, consistent with current CDC guidelines. CONCLUSION: Adherence to CDC-recommended therapy was high for patients with genital chlamydial infections at these two managed care organizations.     

The social organization of commercial sex work in Moscow,Russia

BACKGROUND: Increased poverty, unemployment, and migration place the Russian population at high risk for sexually transmitted infections (STIs). A qualitative study was undertaken to clarify the organization of sex work and describe the likely contributions of different types of sex work to disease transmission. GOAL: The goal of the study was to describe the social-organizational patterns of sex work in Moscow, Russia. STUDY DESIGN: Four qualitative data collection methods were used: semistructured telephone interviews, semistructured face-to-face individual and group interviews with key informants, systematic and unobtrusive naturalistic observations, and geomapping. RESULTS: Intermittent, truck stop, and railway station sex workers may be the most important groups in the dissemination of STIs. Sex work is widely disseminated throughout the city. Identifiable positions in the social organization of street sex work include pimps, assistant female pimps, guards, drivers, "indicators," the sex workers themselves, and recruitment "pluckers." CONCLUSION: The Moscow sex market may be an adjustive response of the social system to the economic pressures in Russia. Sex work in Moscow has great potential for disseminating STIs throughout Russia and beyond. Understanding of these issues may enhance the impact of STI prevention programs.     

The emotional experience of intercourse and sexually transmitted diseases: a decision-tree analysis

BACKGROUND: Epidemiologic data document high risks for many sexually transmitted diseases (STDs) among US adolescents and young adults. GOAL: This case-control study used decision trees to investigate the relationship between STD incidence and emotional reactions to intercourse. STUDY DESIGN: For this study, 188 adolescents and young adults (mean age, 24.9 years [SD = 8.2]) at a regional public STD clinic completed a behavioral and psychological questionnaire and underwent a workup for STD. RESULTS: The prevalence of STD in this group was 44.8%. Decision-tree analysis identified emotional reactions to intercourse that were associated with STD diagnosis for some patients: feeling good about oneself after sex half the time or less (OR = 3.21; 95% CI = 1.73-5.95), feeling comfortable during sex half the time or less (OR = 2.17; 95% CI = 1.07-4.40), and feeling angry after sex (OR = 1.90; 95% CI = 0.91-3.99). Findings of a logistic regression model of emotional reactions to intercourse were significant (chi-square = 24.6; df = 8; P < 0.002), but adding behavioral variables did not improve prediction. CONCLUSIONS: For some of these young adults at the time of life when they are at highest risk of STD, emotional factors have higher odds ratios for STD diagnosis than the traditionally assessed behavioral variables. This underscores the need for interventions targeted to specific subgroups and for readily available mental health services.     

Do the Physical and Histologic Features and Time Course in Acute Generalized Exanthematous Pustulosis Reflect a Pattern of Cytokine Dysregulation?

Background: Acute generalized exanthematous pustulosis (AGEP) is characterized by fever and an indurated erythematous eruption early, with the development of nonfollicular pinhead sterile pustules on an erythematous background. The eruption progresses and resolves relatively rapidly. Although drugs are believed to be the major etiologic agents, other immune modulators, including infections, heavy metals, and radiation, have been implicated. Objective: The purpose of this study was to document underlying diseases in patients with AGEP and to determine if this data and the histologic features suggested an underlying pattern of immune dysregulation. Methods: Twenty-one patients with new or recurrent episodes of AGEP were questioned concerning underlying diseases. The histopathologic features seen in the biopsy sections and the approximate time of biopsy during the course of their eruptions were recorded. Results: Two patients had a history of psoriasis and one patient had a family history of psoriasis, two patients had diagnoses of sarcoid, two patients had inflammatory bowel disease, one had autoimmune thyroiditis, and one patient had multiple sclerosis. Biopsies done at the onset of the eruption showed marked to moderate papillary dermal edema and a mixed dermal inflammatory infiltrate. Shortly thereafter, biopsies showed spongiform pustules within the epidermis and occasional dyskeratotic cells with residual perivascular dermal edema. Although no definitive vasculitis was seen, there was leukocytoclasis within the dermal infiltrate in the majority of biopsy specimens performed more than 48 hours after the onset of the eruption. Conclusion: The histologic features seen in AGEP and the disease associations suggest that patients who develop this eruption may have an underlying tendency for development of a pattern of immune dysregulation characterized by a T helper-1 cytokine pattern.