Publications

Knee injuries are common in sports activities. Understanding the mechanisms of injury allows for better treatment of these injuries and for the development of effective prevention programmes. Tibial torque and knee flexion angle have been associated with several mechanisms of injury in the knee. This article focuses on the injury to the anterior cruciate ligament (ACL), the posterior cruciate ligament (PCL) and the meniscus of the knee as they relate to knee flexion angle and tibial torque. Hyperflexion and hyperextension with the application of tibial torque have both been implicated in the mechanism of ACL injury. A combination of anterior tibial force and internal tibial torque near full extension puts the ACL at high risk for injury. Hyperflexion also increases ACL force; however, in this position, internal and external tibial torque only minimally increase ACL force. Several successful prevention programmes have been based on these biomechanical factors. Injury to the PCL typically occurs in a flexed or hyperflexed knee position. The effects of application of a tibial torque, both internally and externally, remains controversial. Biomechanical studies have shown an increase in PCL force with knee flexion and the application of internal tibial torque, while others have shown that PCL-deficient knees have greater external tibial rotation. The meniscus must endure greater compressive loads at higher flexion angles of the knee and, as a result, are more prone to injury in these positions. In addition, ACL deficiency puts the meniscus at greater risk for injury. Reducing the forces on the ACL, PCL and meniscus during athletic activity through training, the use of appropriate equipment and safe surfaces will help to reduce injury to these structures.

BACKGROUND

This paper evaluates the replicability of an NCI-funded didactic/experiential program to increase the diversity of doctorally-prepared cancer disparities investigators.

METHODS

The program was developed and operated successfully for three years in Northern California when a replication was established at UCLA. Feasibility, process, impact, and outcome measures on UCSF and UCLA summer-institute participants were compared.

RESULTS

Average participant rankings of the influence of the program on intention to apply for a doctorate were 9.1/10 (UCSF) and 8.6/10 (UCLA). A total of 22.5% of UCSF and 10% of UCLA participants have enrolled in, been accepted by, or completed doctoral programs. Among these alumni, 68% (21/31) of UCSF and 60% (3/5) of UCLA participants plan to conduct their doctoral research in cancer control.

CONCLUSIONS

This program has been successfully replicated and has met its objective to increase the pipeline of ethnically diverse doctoral-level public health researchers. Expansion of the program to other regions of the US is feasible and indicated.

An abnormal mammography finding constitutes a stressful event that may increase vulnerability by developing or intensifying pre-existing psychological morbidity. We evaluated depressive symptoms using the Composite International Diagnostic Interview among women of four ethnic groups who had an abnormal mammography result controlling for the effect of demographic, psychosocial and medical factors on recent onset of depressive symptoms. Telephone surveys were conducted among women aged 40-80 years recruited from four clinical sites in the San Francisco Bay Area after receiving a screening mammography result that was classified as abnormal but probably benign, suspicious or highly suspicious, or indeterminate using standard criteria. Among the 910 women who completed the interview, mean age was 56 (S.D.=10), 42% were White, 19% Latina, 25% African American, and 14% Asian. Prevalence of lifetime depressive symptoms was 44%, and 11% of women had symptoms in the previous month. Multivariate logistic regression models showed that Asian ethnicity, annual income >$10 000 and weekly attendance at religious services were significantly associated with decreased depressive symptoms. Having an indeterminate result on mammography and being on disability were significantly associated with more depressive symptoms. Reporting a first episode of depression more than a year before the interview was associated with significant increase in depressive symptoms in the month prior to the interview regardless of mammography result. Women with an indeterminate interpretation on mammography were at greater risk of depressive episode in the month prior to the interview compared to women with probably benign results (odds ratio=2.41; 95% CI=1.09-5.31) or with a suspicious finding. Clinicians need to consider depression as a possible consequence after an abnormal mammography result.

Hepatitis C virus (HCV) has become a significant source of morbidity and mortality in HIV-infected patients. However, little is known about the clinical presentation and course of acute HCV infection in this population. This study reports the outcomes of acute HCV infection in 9 HIV-infected men. Sex with men was the only reported risk factor for HCV infection in 6 of the subjects. Clinical presentation of acute HCV ranged from incidentally discovered elevated transaminases to severe liver dysfunction requiring hospitalization. At the time of HCV diagnosis, 8 of 9 patients had CD4+ counts >250 cells/mm(3), and 6 had HIV viral loads of < or =5000 copies/mL. Eight patients were receiving antiretroviral therapy. Outcome of these acute HCV infections varied. Five patients experienced virologic clearance, 2 in whom virus cleared spontaneously and 3 who were treated with pegylated interferon and ribavirin. Four patients developed chronic infection, one of whom had a relapse during HCV treatment and 3 of whom were untreated. All 4 patients to whom HCV therapy was administered experienced significant anemia or neutropenia, necessitating dose reduction or support with growth factors. Prompt recognition of acute HCV infection may minimize antiretroviral treatment interruption and will allow early treatment, which may improve virologic clearance. Unexplained transaminase elevations in HIV-infected patients, including men who have sex with men, should trigger an evaluation for acute HCV infection.

Reductive prodrugs, mitomycin C and 5-aziridinyl-2,4-dinitrobenzamide (CB 1954), are nontoxic in their native form but become highly toxic upon reduction. Their effectiveness in cancer chemotherapy can be enhanced by delivering to tumors enzymes with improved prodrug reduction kinetics. We report the discovery of a new prodrug-reducing enzyme, YieF, from Escherichia coli, and the improvement of its kinetics for reducing mitomycin C and CB 1954. A YieF-derived enzyme, Y6, killed HeLa spinner cells with >or=5-fold efficiency than the wild-type enzymes, YieF and NfsA, at a variety of drug and enzyme concentrations and incubation times. With adhered HeLa cells and Salmonella typhimurium SL 7838 bacteria as enzyme delivery vehicle, at least an order of magnitude less of Y6-producing bacteria were required to kill >90% of tumor cells compared with bacteria expressing the wild-type enzymes, which at a comparable level killed < 5% of the cells. Thus, Y6 is a promising enzyme for use in cancer chemotherapy, and Salmonella strain SL 7838, which specifically targets tumors, may be used to deliver the prodrug-activating enzymes to tumors.

OBJECTIVES

To evaluate the prevalence of and factors associated with depression among HIV-infected homeless and marginally housed men.

DESIGN

Cross-sectional study.

PARTICIPANTS AND SETTING

Homeless and marginally housed men living with HIV in San Francisco identified from the Research on Access to Care in the Homeless (REACH) Cohort.

MEASUREMENTS

The primary outcome was symptoms of depression, as measured by the Beck Depression Inventory (BDI). Multivariate logistic regression was used to identify associations of sociodemographic characteristics, drug and alcohol use, housing status, jail status, having a representative payee, health care utilization, and CD4 T lymphocyte counts.

RESULTS

Among 239 men, 134 (56%) respondents screened positive for depression. Variables associated with depression in multivariate analysis included white race (adjusted odds ratio [AOR]=2.2, confidence interval [CI]=1.3 to 3.9), having a representative payee (AOR=2.4, CI=1.3 to 4.2), heavy alcohol consumption (AOR=4.7, CI=1.3 to 17.1), and recently missed medical appointments (AOR=2.6, CI=1.4 to 4.8).

CONCLUSIONS

Depression is a major comorbidity among the HIV-infected urban poor. Given that missed medical appointments and alcohol use are likely indicators of depression and contributors to continued depression, alternate points of contact are necessary with many homeless individuals. Providers may consider partnering with payees to improve follow-up with individuals who are HIV-positive, homeless, and depressed.

Host immunity plays an important role in response to antimalarial therapy but is poorly understood. To test whether T cell activation is a risk factor for antimalarial treatment failure, we studied CD4(+) and CD8(+) T cell activation in 31 human immunodeficiency virus-negative Ugandan patients 5-37 years of age who were treated for uncomplicated Plasmodium falciparum malaria. Increased CD4(+) T cell activation, as indicated by co-expression of HLA-DR and CD38, was an independent risk factor for treatment failure (hazard ratio = 2.45, 95% confidence interval = 1.02-5.89, P = 0.05) in multivariate analysis controlling for age, baseline temperature, and pre-treatment parasite density. The results provide insight into the role of cellular immunity in response to antimalarial therapy and underscore the need to investigate the mechanisms behind immune activation.

INTRODUCTION

Abnormalities of serum sodium are common after subarachnoid hemorrhage (SAH) and have been linked to poor outcome. This study analyzed whether abnormal serum sodium levels are associated with cardiac outcomes and mortality after subarachnoid hemorrhage (SAH).

METHODS

In a prospective cohort study of SAH patients, the primary predictor variable was subjects' sodium level. Hypernatremia was defined as sodium >143 mmol/L and hyponatremia was <133 mmol/L. Cardiac troponin I (cTi) was measured and echocardiography was performed on three study days. Dichotomous outcome variables were cTi > 1.0 microg/L, left-ventricular ejection fraction (LVEF) <50%, presence (vs absence) of regional wall motion abnormalities (RWMA) of the LV, pulmonary edema, and death. Additional analyses studied the degree of hypernatremia and sodium supplementation, and the temporal relationship between hypernatremia and cardiac outcomes.

RESULTS

The study included 214 subjects. Forty-eight subjects (22%) were hypernatremic on at least one study day, and 45 (21%) were hyponatremic. After multivariate adjustment, hypernatremia was an independent predictor of LVEF <50% (OR 4.7, CI 1.3-16.2, p = 0.015), elevated cTi (OR 3.7, CI 1.2-11.9, p = 0.028), and pulmonary edema (OR 4.1 CI 1.4-1.5, p = 0.008). It was not, however a statistically significant predictor of mortality (p = 0.075).

CONCLUSION

In the acute period after SAH, hypernatremia is associated with adverse cardiac outcomes and death. SAH patients with hypernatremia should be monitored for evidence of cardiac dysfunction.

Socio-economic status (SES) may affect health status in airway disease at the individual and area level. In a cohort of adults with asthma, rhinitis or both conditions, questionnaire-derived individual-level SES and principal components analysis (PCA) of census data for area-level SES factors were used. Regression analysis was utilised to study the associations among individual- and area-level SES for the following four health status measures: severity of asthma scores and the Short Form-12 Physical Component Scale (SF-12 PCS) (n = 404); asthma-specific quality of life (QoL) scores (n = 340); and forced expiratory volume in one second (FEV1) per cent predicted (n = 218). PCA yielded a two-factor solution for area-level SES. Factor 1 (lower area-level SES) was significantly associated with poorer SF-12 PCS and worse asthma QoL. These associations remained significant after adding individual-level SES. Factor 1 was also significantly associated with severity of asthma scores, but not after addition of the individual-level SES. Factor 2 (suburban area-level SES) was associated with lower FEV1 per cent predicted in combined area-level and individual SES models. In conclusion, area-level socio-economic status is linked to some, but not all, of the studied health status measures after taking into account individual-level socio-economic status.

OBJECTIVE

To evaluate the association between spondylosis deformans and clinical signs of intervertebral disk disease (IVDD) in dogs.

DESIGN

Retrospective case series.

ANIMALS

210 dogs.

PROCEDURE

Records of 172 dogs with clinical signs of IVDD and 38 dogs with other neurologic disorders were reviewed. Signalment, sites of spondylosis, severity of associated osteophytosis, type of disk herniation, and duration of signs were recorded.

RESULTS

Dogs with IVDD had significantly fewer sites of involvement and lower grades of spondylosis deformans, compared with those in the non-IVDD group. When groups were adjusted for age and weight via multivariate linear regression, there were no differences in severity of osteophytosis or number of affected sites. Dogs with type II disk disease had higher numbers of affected sites and more severe changes, compared with dogs with type I disk herniation. There was no difference between groups in the rate at which IVDD was diagnosed at sites of spondylosis, compared with the rate at which IVDD was diagnosed in unaffected disk spaces. Areas of spondylosis were closer to sites of IVDD that elicited clinical signs than to randomly chosen intervertebral spaces, and distances between sites of spondylosis and sites of IVDD had a bimodal appearance.

CONCLUSIONS AND CLINICAL RELEVANCE

An association may exist between radiographically apparent spondylosis and type II disk disease; type I disk disease was not associated with spondylosis. Spondylosis in radiographs of dogs with suspected type I disk disease is not clinically important. Spatial associations among sites of spondylosis and sites of IVDD may be coincidental or associated with vertebral column biomechanics.