Effect of cocoa and green tea on biomarkers of glucose regulation, oxidative stress, inflammation and hemostasis in obese adults at risk for insulin resistance.

BACKGROUND/OBJECTIVES: Flavanols may provide protection against insulin resistance, but little is known about the amounts and types of flavanols that may be efficacious. SUBJECTS/METHODS: This study was designed to determine whether cocoa flavanols, over a range of intakes, improve biomarkers of glucose regulation, inflammation and hemostasis in obese adults at risk for insulin resistance. As an adjunct, green tea and cocoa flavanols were compared for their ability to modulate these biomarkers. In a randomized crossover design, 20 adults consumed a controlled diet for 5 days along with four cocoa beverages containing 30-900 mg flavanol per day, or tea matched to a cocoa beverage for monomeric flavanol content. RESULTS: Cocoa beverages produced no significant changes in glucose, insulin, total area under the concentration-time curve (AUC) for glucose or total insulin AUC. As the dose of cocoa flavanols increased, total 8-isoprostane concentrations were lowered (linear contrast, P=0.02), as were C-reactive protein (CRP) concentrations (linear contrast, P=0.01). The relationship between cocoa flavanol levels and interleukin-6 (IL-6) concentrations was quadratic, suggesting that a maximum effective dose was achieved (quadratic contrast, P=0.01). There were no significant effects on measured indices of glucose regulation, nor on those of total 8-isoprostane, CRP and IL-6 concentrations, when cocoa and green tea were compared. However, relative to cocoa, green tea lowered fibrinogen concentrations (P=0.0003). CONCLUSIONS: Short-term intake of cocoa and green tea flavanols does not appear to improve glucose metabolism; they do affect selected markers of one or more measures of oxidative stress, inflammation or hemostasis in obese adults at risk for insulin resistance.

Bartonella species antibodies and hyperglobulinemia in privately owned cats.

BACKGROUND: Bartonella species are zoonotic agents and primary pathogens in cats. Hyperglobulinemia has been associated with bartonellosis in humans and cats. HYPOTHESIS/OBJECTIVES: To evaluate for associations between Bartonella species immunoglobulin G (IgG) antibodies and serum biochemistry panel results in privately owned cats. ANIMALS: 1,477 privately owned cats. METHODS: Residual sera were collected after biochemical evaluation for this prospective, cross-sectional serosurvey. Bartonella species IgG ELISA was performed with a cutoff value of ≥ 1 : 64. Stepwise logistic regression analysis was performed with the endpoint titer as the outcome variable. The final statistical model included age, albumin, ALP activity, ALT activity, bilirubin, creatinine, glucose, and globulin as covariates. Serum protein electrophoresis was performed with serum from 50 cats with and without antibodies to Bartonella species and hyperglobulinemia. Sera from cats seropositive to Bartonella species and with hyperglobulinemia were assessed for evidence of exposure to other infectious agents associated with hyperglobulinemia. RESULTS: Risk of seropositivity to Bartonella species was positively associated with the natural log of globulin concentration (OR = 11.90, 95% CI 6.15-23.02, P < .0001), and inversely associated with the natural log of glucose concentration (OR = 0.66, 95% CI 0.50-0.87, P = .004). Another explanation for hyperglobulinemia was not identified for most cats with Bartonella species antibodies. Hyperglobulinemia was primarily caused by polyclonal gammopathy in cats that were seronegative and seropositive for Bartonella species. CONCLUSIONS AND CLINICAL IMPORTANCE: Hyperglobulinemia was significantly associated with seropositivity to Bartonella species. Testing for bartonellosis is warranted in cats with unexplained hyperglobulinemia and clinical or laboratory findings suggestive of bartonellosis.

Demonstrating bioequivalence using clinical endpoint studies.

For drug products not amenable to blood level studies, clinical endpoint studies have been used as an indirect measure of formulation difference in bioavailability between test and reference products. However, clinical endpoint studies are not as sensitive in detecting formulation differences as blood level studies and offer numerous challenges to both regulatory authorities and sponsors. The objective of this article is not to suggest new regulatory policies, but to explore new methodologies and alternative solutions to clinical endpoint bioequivalence (BE) studies, which are used when a blood level study is not considered to be appropriate. To achieve this objective, this article identifies situations where a clinical endpoint study might be appropriate, lists the advantages and disadvantages of this type of study design, and discusses possible alternative solutions. It is concluded that future evidence-based research is needed to explore new methodologies such as clinical trial simulations of various study designs, new statistical methods, and new in vitro methods to demonstrate BE.

Marbofloxacin for the treatment of experimentally induced Mycoplasma haemofelis infection in cats.

BACKGROUND: Administration of tetracyclines or fluoroquinolones is associated with improvement in clinical and laboratory abnormalities in cats infected with Mycoplasma haemofelis. No treatment protocol has consistently eliminated the organism, and antimicrobial susceptibility may vary among M. haemofelis isolates. Continued search for effective therapies is warranted. HYPOTHESIS: Marbofloxacin administered at the onset of clinical illness will be safe and effective for the treatment of M. haemofelis. ANIMALS: Fourteen young adult, laboratory-reared cats housed together in a specific pathogen-free facility. METHODS: Twelve cats were inoculated IV with 2.0 mL of blood from 2 M. haemofelis positive cats. Clinical parameters were assessed daily. CBC and hemoplasma polymerase chain reaction (PCR) assay were performed before inoculation, weekly for 1-3 weeks postinoculation (PI) and twice weekly 3-6 weeks PI. Treatment with marbofloxacin (2.75 mg/kg PO daily for 14 days) was initiated in 6 randomly selected cats when PCV was <30% or fever was >102.5 degrees F (39.2 degrees C). Cats that were PCR positive on day 7 of therapy were treated for 28 days. Cats that were PCR negative on day 42 PI were treated with 20 mg/kg methylprednisolone acetate IM on day 50 PI. RESULTS: Significant differences between groups on some days after inoculation included higher PCV and red blood cell counts, lower mean cell volume, and higher mean cell hemoglobin content in marbofloxacin-treated cats. No differences in PCR assay results were noted between groups. CONCLUSIONS AND CLINICAL IMPORTANCE: Marbofloxacin was safe and resulted in more rapid hematologic improvement in M. haemofelis-infected cats, but did not change clinical scores and did not consistently eliminate infection.

Ex vivo analysis of topotecan: advancing the application of laboratory-based clinical therapeutics.

Topotecan is currently approved for relapsed small-cell lung cancer and ovarian cancer. Topotecan's efficacy in the second-line setting and novel mechanism of action suggest broad antitumour activity. We utilised a clinically validated, cell-death, ex vivo assay in human tumour explants to examine the activity profile of topotecan alone and in combination with other antitumour agents. Serial dilutions of topotecan alone and in combination with other cytotoxic agents were applied to biopsy specimens of non-small-cell lung cancer (NSCLC) and breast, colon, and prostate cancers. Dose-response curves were interpolated to provide 50% lethal concentrations (LC(50)). The degree of synergy (by median effect) and normalised Z-scores (raw scores converted to relative activity distributed around the mean) were then computed. Single-agent activity was observed for topotecan in all four tumour types. In 57 chemotherapy-naive specimens, NSCLC revealed the highest activity, demonstrated by the lowest LC(50) value (0.26+/-0.06 microg ml(-1); P=0.002). Overall, previously treated and chemotherapy-naive specimens revealed no significant differences in mean LC(50)'s. Synergy was observed for several combinations, including topotecan plus cisplatin in prostate and for topotecan plus 5-fluorouracil in breast cancers. The Z-score analyses conducted suggest activity for previously unexplored drug regimens, including topotecan plus 5-fluorouracil, vinorelbine, and mitomycin-C in NSCLC and breast cancer. Phase II studies are underway to determine the degree to which these ex vivo findings will translate into improved clinical results.

Inoculation of two genotypes of Hemobartonella felis (California and Ohio variants) to induce infection in cats and the response to treatment with azithromycin.

OBJECTIVES: To describe clinical and laboratory findings associated with cats experimentally infected by inoculation with the 2 recognized genotypes of Hemobartonella felis (small variant, Hfsm; large variant, Hflg) and to determine the response of cats to treatment with azithromycin. ANIMALS: 18 young adult domestic shorthair cats of both sexes. PROCEDURES: Cats were inoculated with H felis and monitored weekly, using CBC counts and a polymerase chain reaction (PCR) designed to detect both genetic variants of H felis. Beginning 26 days after inoculation, 11 cats were administered azithromycin (15 mg/kg of body weight, PO, q 12 h, for 7 days). RESULTS: Inoculation resulted in coinfection with Hflg and Hfsm, and both variants were detected by PCR. Clinical abnormalities and anemia were most severe in Hflg- and dual-infected cats. Results of PCR and CBC were positive for H felis in 112/112 (100%) and 42/112 (37.5%), respectively, samples collected after inoculation. Administration of azithromycin had little effect on clinical variables, including anemia. All cats, regardless of treatment with azithromycin, had positive results for the PCR at the end of the study period. CONCLUSIONS AND CLINICAL RELEVANCE: In these cats, Hflg was more pathogenic than Hfsm, and coinfection with both variants was detected. Results of the PCR were superior to results of CBC for detecting infection with H felis. Azithromycin administered at the dose and duration reported here was not efficacious for the treatment of cats with hemobartonellosis.

Safety, efficacy, and immunogenicity of a modified-live equine influenza virus vaccine in ponies after induction of exercise-induced immunosuppression.

OBJECTIVE: To determine safety, efficacy, and immunogenicity of an intranasal cold-adapted modified-live equine influenza virus vaccine administered to ponies following induction of exercise-induced immunosuppression. DESIGN: Prospective study. ANIMALS: Fifteen 9- to 15-month old ponies that had not had influenza. PROCEDURE: Five ponies were vaccinated after 5 days of strenuous exercise on a high-speed treadmill, 5 were vaccinated without undergoing exercise, and 5 were not vaccinated or exercised and served as controls. Three months later, all ponies were challenged by nebulization of homologous equine influenza virus. Clinical and hematologic responses and viral shedding were monitored, and serum and nasal secretions were collected for determination of influenza-virus-specific antibody isotype responses. RESULTS: Exercise caused immunosuppression, as indicated by depression of lymphocyte proliferation in response to pokeweed mitogen. Vaccination did not result in adverse clinical effects, and none of the vaccinated ponies developed clinical signs of infection following challenge exposure. In contrast, challenge exposure caused marked clinical signs of respiratory tract disease in 4 control ponies. Vaccinated and control ponies shed virus after challenge exposure. Antibody responses to vaccination were restricted to serum IgGa and IgGb responses in both vaccination groups. After challenge exposure, ponies in all groups generated serum IgGa and IgGb and nasal IgA responses. Patterns of serum hemagglutination inhibition titers were similar to patterns of IgGa and IgGb responses. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggested that administration of this MLV vaccine to ponies with exercise-induced immunosuppression was safe and that administration of a single dose to ponies provided clinical protection 3 months later.

Patients' perceptions of medical students in a longitudinal family medicine clerkship.

BACKGROUND: Although educational characteristics of ambulatory clinical environments are becoming clearer, less is known concerning patient opinions about participating in medical student instruction in ambulatory settings. Such perceptions may have an important influence on recruitment and retention of community faculty. METHODS: Surveys were administered to 121 patients seen by medical students during a longitudinal family medicine clerkship. The survey explored patients' opinions regarding the extent of direct student involvement in their care, students'competence, and patient feelings about participating in medical student instruction. RESULTS: Patients felt that students were highly involved in providing care and that they performed competently and professionally. Patients found participation in medical education enjoyable, not excessively time-consuming or disruptive, and believed that students' participation improved the quality of care they received. CONCLUSIONS: Patients in our family medicine clerkship do not have negative perceptions about their participation in medical student education. In fact, this study suggests that such participation may actually enhance patient satisfaction.

Occupational human immunodeficiency virus exposure among residents and medical students: an analysis of 5-year follow-up data.

BACKGROUND: Findings of a needlestick survey at our institution yielded an estimate that 1 case of occupationally acquired human immunodeficiency virus (HIV) among the approximately 1100 residents and third- and fourth-year medical students would potentially occur every 2 to 3 years, and also revealed types of exposures, circumstances, rates of reporting, and reasons for not reporting. OBJECTIVE: The present study is a 5-year follow-up study to investigate changes in these parameters. METHODS: A self-administered, anonymous 2-page questionnaire covering occupational exposures and other risk factors was distributed to medical students in classes, and to residents in grand rounds and required conferences. The response rate was 71%. RESULTS: The incidence of needlestick accidents dropped dramatically over 5 years (1994-1995 vs 1989-1990), especially for surgical residents. Because the proportion of known sources positive for HIV increased over the same period, estimates of occupational HIV risk remain essentially the same, with a projection that 1 student or resident would be expected to experience an occupationally acquired HIV infection approximately every 2 years. The nonoccupational risk for this population, in contrast, seems to be lower than in their age group as a whole. CONCLUSIONS: While the decrease in overall occupational exposures (especially for surgical residents) coupled with slight increases in rates of exposure documentation and use of universal precautions constitute positive findings, the increased proportion of exposure sources who are HIV positive leads to an unchanged estimate of occupational HIV risk for residents and students. Study findings therefore support the continued need for educational efforts aimed at prevention, along with timely dissemination of advances in approaches to postexposure prophylaxis.

Assessing the acquisition of core clinical skills through the use of serial standardized patient assessments.

PURPOSE: Students in many medical schools now undergo multiple standardized-patient-based assessments. In this study, the authors examine the ability of such serial assessments to detect interval learning. METHOD: Twenty-one students from the University of California, Irvine, College of Medicine, class of 1999, underwent a clinical skills appraisal after three months of their third-year instruction. After nine months, all 89 members of that class completed an OSCE. Subsequently, all 87 students in the class of 2000 also completed clinical skills assessments after their third and ninth months of third-year instruction. All of these exercises included identical or similar stations measuring history, physical examination, and communication skills. Communication skills were measured somewhat differently during some of the exercises, using checklists that were either "content-" or "process-"oriented. The authors compared the performances for all groups. RESULTS: Both classes demonstrated significant improvement in physical examination performance, while their history performances remained unchanged. According to the assessments, their communication skills deteriorated over the course of their third-year instruction. Repeated exposures to similar or identical cases on the serial assessments did not impact the students' performances. Both content- and process-oriented measures of communication skills yielded highly similar results. CONCLUSIONS: Serial assessments using standardized patients can detect interval changes in performance that are independent of repeated exposures to similar or identical cases. Changes detected using this approach may have important curricular implications.

Randomized clinical trial of a diagnostic instrument for pain complaints.

BACKGROUND AND OBJECTIVES: This study evaluated use of the patient-administered Personal Pain Tracker in ambulatory primary care practice and tested the hypothesis that use of the instrument is associated with greater patient satisfaction with physician-patient communication regarding pain. METHODS: This randomized clinical trial was conducted in the offices of 12 family physicians practicing in Los Angeles and Orange Counties in Southern California. Study subjects consisted of 79 patients who presented with pain complaints during the study's enrollment period and who conformed to the inclusion and exclusion criteria. Patients randomized to the experimental arm of the study received and completed the Pain Tracker, and both these patients and control group patients participated in a telephone interview with an investigator 1 week subsequent to their visit. RESULTS: Regardless of the specific nature or cause of their pain, patients randomized to the Pain Tracker group were substantially more likely to report that their physicians felt that their pain was genuine and were concerned about it, asked enough questions about the pain and listened carefully, gave them a chance to provide a complete explanation, and performed a thorough examination. Patients in the Pain Tracker group also reported a higher level of overall satisfaction with their visit. CONCLUSIONS: Use of the Pain Tracker instrument improves patients' perceptions of the quality of physician-patient communication regarding pain complaints and results in greater overall satisfaction with medical visits.

Influence of continuous growth hormone or insulin-like growth factor I administration in adult female chickens.

A series of studies was conducted to determine whether growth hormone (GH) exerts effects on adult female chickens. Recombinant chicken GH (rcGH) was administered continuously via osmotic minipumps. No consistent effects of rcGH treatment were observed on reproductive indices. Hens receiving rcGH treatment for 10 days exhibited hepatomegaly and showed a tendency (P < 0.1) for increased spleen and thymus weights. Moreover, there were increases in the circulating concentrations of insulin-like growth factor-I (IGF-I) and IGF-binding proteins (IGF-BPs) (22-kDa IGF-BP after 2, 5, and 10 days; 28-kDa IGF-BP after 5 and 10 days; and 36-kDa IGF-BP after 10 days) with rcGH treatment. To determine whether the changes in IGF-BPs were due directly to GH or indirectly via IGF-I, the effects of the continuous administration of rcGH or recombinant human IGF-I (rhIGF-I) were compared. While rcGH again elevated the circulating levels of 28- and 36-kDa IGF-BPs, no such effect was observed with rhIGF-I treatment. However, both treatments exerted similar effects in depressing pituitary GH mRNA levels and elevating plasma concentrations of IGF-I. It is concluded that GH directly elevates circulating concentrations of IGF-I and IGF-BPs, but the negative feedback effect on GH synthesis is mediated via IGF-I.

Generational differences in psychosocial adaptation and predictors of psychological distress in a population of recent Vietnamese immigrants.

While first-wave Vietnamese immigrants adapted well to life in the United States, subsequent immigrants have had greater adjustment difficulties, including more evidence of psychological distress. This study aimed to analyze psychosocial adaptation differences among three generations of recent Vietnamese immigrants, as well as to examine predictors of mental distress in the sample as a whole. A community sample of 184 recent Vietnamese immigrants, categorized as either elderly, middle-aged, or young adults, was assessed for levels of psychological distress, including depression, anxiety, and PTSD, as well as family conflict, dissatisfaction with life in the U.S., acculturation and biculturalism, social support, coping, and premigratory stressors. Young Vietnamese adults were most acculturated, most bicultural, and reported themselves as healthiest and least depressed. They were most often working, least often on welfare, and had the highest family income. However, they also reported most dissatisfaction with their current lives in the U.S. and most family conflict. Regression analysis explaining approximately one-quarter of the variance in mental distress implicated current dissatisfaction with and lack of adjustment of life in the United States, as well as greater acculturation and increased family conflict. Although young adults scored significantly higher than other generations on most of the risk factors for psychological distress, they appeared to be buffered against poorer mental health outcomes by factors of generation and perceived positive overall well-being. In terms of testing a predictive model of psychological distress, this study found current adjustment factors significantly more important in determining mental health outcomes than premigratory stressors such as war-related traumas.

Comparative study of the incidence and severity of degenerative change in the transition zones after instrumented versus noninstrumented fusions of the lumbar spine.

The purpose of this study was to determine whether the addition of pedicle screws and rods to a fusion of two or more vertebrae of the lowest three motion segments of the lumbar spine increases the incidence or severity of transition zone change (TZC) above or below the fused area. A study group of 52 patients who had a fusion with fixation and a control group of 31 who had a nearly identical operation but without fixation were obtained. Radiographs and computed tomography scans of the area of study were taken preoperatively and were repeated approximately 7 years after the operation. Results showed that the addition of pedicle screw fixation does not increase the incidence or severity of TZC in the first 7 years after surgery.

Sexual behavior and AIDS-related knowledge among community college students in Orange County, California.

Whereas college students are not identified as a high-risk group for acquiring the HIV infection, they exhibit high-risk behaviors consistent with their age group, including multiple sexual partners and high rates of unprotected intercourse. This study was conducted to determine levels of HIV-related sexual behavior, along with knowledge and attitudes among students attending community colleges in a relatively affluent multiethnic community. This study used a random sample survey (N = 319) of students attending selected classes at four community colleges in Orange County, California, to assess HIV/AIDS knowledge, attitudes, and patterns of past and present sexual behavior. The level of student knowledge concerning HIV disease was found to be relatively high, and pronounced differences in knowledge and sexual permissiveness were identified as a function of ethnicity and religion, with Asians showing lower knowledge and lower concern about HIV, and religion/religiosity related to these variables and also to levels of sexual permissiveness. Respondents' comfort in asking a partner about his/her sexual history was positively associated with their level of self-esteem, and negatively related to peer pressure in this population. As in previous studies of college populations, HIV knowledge per se does not confer a protective effect against high-risk behavior. However, knowledge was found to be an enabling factor with regard to students' comfort levels in asking about their partner's sexual histories, and in requesting that partners take an AIDS test.

Willingness to treat HIV-positive patients at different stages of medical education and experience.

The willingness of physicians to provide care to HIV-positive patients has been linked to a number of attitudinal factors, but little is known concerning the impact of premedical, medical, and residency training on these factors. The purpose of this study is to elicit responses to the same series of questions concerning HIV and its treatment from respondents at different stages of training, to detect trends in attitudes and to measure the impact of those attitudes on willingness to provide care for HIV/AIDS patients. Study data come from a cross-sectional survey (n = 249) of respondents across the training continuum, from premedical students to faculty physicians, using a self-administered questionnaire at a single medical school. The response rate was 59.6%. The study showed significant decreases in personal fear and misgivings concerning HIV, coupled with a substantial decrease in the perceived need for testing of non-high-risk individuals, as respondents gained additional education and training. Overall, the intent to treat HIV did not change significantly by training level, but multivariate analyses showed that while the initially strong influence of attitudes toward AIDS and its attendant risks diminishes, comfort relative to being around homosexuals per se continues to exert an impact on the intent to treat. Appropriate use of protective measures when providing care becomes far more common once individuals enter their clinical training years. The impact of medical education through its entire continuum therefore shows a positive impact on attitudes toward HIV, despite the absence of a significant trend in respondents' stated intent to treat. However, negative attitudes toward homosexuals continue to exert a negative influence on intent to treat that endures into the clinical training years.

Do patients want to talk to their physicians about organ donation? Attitudes and knowledge about organ donation: a study of Orange County, California residents.

This study surveyed Orange County, California residents to determine their attitudes and knowledge about organ donation and in particular to determine what factors influence the decision to donate one's organs upon death. Respondents were recruited from the Orange County Superior Court jury pool (N = 378). Each completed a 44 item questionnaire. Findings from the analysis of Questionnaire Data reveal that nearly three-quarters of respondents had considered donating their organs, yet less than one-third had made arrangements to donate. Having an accurate knowledge about organ donation and being willing to accept a donated organ were particularly robust factors associated with the likelihood to donate. Having spoken with a physician was also a positive factor, yet just 5% of the sample had done so, and two-thirds of respondents did not want to discuss organ donation with their physician. The study's findings suggest that enhanced recruitment may be achieved by focusing on education (especially increased emphasis on the family's role) and by targeting both parents and their children. Finally, although physicians are encouraged to discuss organ donation with patients, more information is needed to explain why patients may not want to talk about this topic with their doctors.

Initial experience with a multi-station objective structured teaching skills evaluation.

PURPOSE: To explore the applicability of using an objective structured evaluation to assess community preceptors' teaching performances. METHOD: The authors developed and, in 1996, administered an objective structured teaching evaluation (OSTE) at the University of California, Irvine, College of Medicine. They compared assessments of teaching skills made by faculty observers and standardized students, and examined instrument reliability, realism, and utility. RESULTS: Reliabilities of the OSTE varied with individual stations but, in several instances, approached acceptable standards. Faculty observers' and standardized students' evaluations of preceptors' performances were similar. Participants' feedback indicated that the greatest OSTE-related benefit was derived by the faculty observers. CONCLUSIONS: An OSTE that reflects realistic teaching situations can be successfully developed. Objective structured evaluation can be successfully applied to assessing faculty teaching performance. However, it may be no more discriminating than are student evaluations. An OSTE's utility may be greatest in guiding faculty development initiatives.