Differential affinity of anti-Pr-β-hCG-TT antibodies for hCG and hLH

Sera from four women immunized with the vaccine Pr-β-hCG-TT have been analysed for binding with hCG and hLH. Resolution of Scatchard plots showed the presence of more than one population of antibodies in these sera. In each case the Association Constants (Ka) of a population of antibodies for binding with hCG were distinctly higher than those for hLH. Results indicate the likely presence in β-hCG of determinants and/or conformations immunologically unique to hCG besides common regions.     

Chromoblastomycosis

A 70-year-old male agriculturist from a rural area presented with a history of a painless verrucous lesion over the medial aspect of the left leg for 1 year following abrasion by a branch of a coconut tree. KOH preparation of the skin biopsy showed evidence of fungal elements. Cladophilalospora sp. was isolated in culture. The case was diagnosed as chromoblastomycosis. As there was no response to itraconazole, complete surgical resection of the lesion was done. At follow-up after 1 year there was clinical as well as mycological cure.     

Huntington's disease: new frontiers for molecular and cell therapy

Huntington's disease (HD) is an incurable, adult-onset, dominantly inherited neurodegenerative disease, caused by a CAG expansion in the 5' coding region of the gene HD [encoding huntingtin (htt), which is ubiquitously expressed in all tissues]. The disease progresses inexorably with devastating clinical effects on motor, cognitive and psychological functions; death occurring approximately 18 years from the time of onset. These clinical symptoms primarily relate to the progressive death of medium-spiny GABA-ergic neurons of the striatum and in the deep layers of the cortex; during the later stages of the disease, the degeneration extends to a variety of brain regions, including the hypothalamus and hippocampus. The mechanism by which mutant htt leads to neuronal cell death and the question of why striatal neurons are targeted both remain to be further investigated. Certainly htt is required for cell survival and impairment of wild-type htt function can be involved in neurodegeneration, but considerable evidence also shows that trinucleotide repeat expansion into glutamine (polyQ domain) endows the protein with a newly acquired toxic activity. The increasing availability of HD animal models have allowed not only to investigate the function of htt, but also to screen and test potential therapeutic drugs in the promising area of neurotherapeutics. So, thorough analysis of these molecular and biochemical events, assessing the validity of candidate mechanisms, provides a means to identify effective therapeutic strategies for cellular repair. Here, the rationale and efficacy of different therapies are compared and alternative therapies are reviewed including intrastriatal transplantation of human fetal striatal tissue to support the cell replacement strategy in HD. Since functional restoration through neuronal replacement probably could be combined with neuroprotective strategies for optimum clinical benefit, in vivo and ex vivo gene therapy for delivery of neuroprotective growth factor molecules are also considered.     

Paired basic science and clinical problem-based learning faculty teaching side by side: do students evaluate them differently?

INTRODUCTION: Many studies have evaluated the desirability of expert versus non-expert facilitators in problem-based learning (PBL), but performance differences between basic science and clinical facilitators has been less studied. In a PBL course at our university, pairs of faculty facilitators (1 clinician, 1 basic scientist) were assigned to student groups to maximise integration of basic science with clinical science. AIMS: This study set out to establish whether students evaluate basic science and clinical faculty members differently when they teach side by side. METHODS: Online questionnaires were used to survey 188 students about their faculty facilitators immediately after they completed each of 3 serial PBL cases. Overall satisfaction was measured using a scale of 1-7 and yes/no responses were gathered from closed questions describing faculty performance. results: Year 1 students rated basic science and clinical facilitators the same, but Year 2 students rated the clinicians higher overall. Year 1 students rated basic scientists higher in their ability to understand the limits of their own knowledge. Year 2 students rated the clinicians higher in several content expertise-linked areas: preparedness, promotion of in-depth understanding, and ability to focus the group, and down-rated the basic scientists for demonstrating overspecialised knowledge. Students' overall ratings of individual faculty best correlated with the qualities of stimulation, focus and preparedness, but not with overspecialisation, excessive interjection of the faculty member's own opinions, and encouragement of psychosocial issue discussion. CONCLUSION: When taught by paired basic science and clinical PBL facilitators, students in Year 1 rated basic science and clinical PBL faculty equally, while Year 2 students rated clinicians more highly overall. The Year 2 difference may be explained by perceived differences in content expertise.     

Correlation of her-2/neu gene amplification with other prognostic and predictive factors in female breast carcinoma

The purpose of this study was to determine if any relationship exists between Her-2/neu gene amplification and estrogen receptor (ER), progesterone receptor (PR), MIB-1, grade, size and age in female breast cancer. Five hundred and eighteen female patients with invasive breast carcinoma, 390 ductal and 128 lobular, in which assessment of Her-2/neu amplification by fluorescence in-situ hybridization (FISH) has been performed, were reviewed retrospectively. Each patient was further assessed for ER, PR, MIB-1, grade, size and age at diagnosis. Chi-square analysis was then used to correlate the above observations. Overall gene amplification was seen in 76 (15%) of the cases, 68 (17%) were ductal and 8 (6%) were lobular. Her-2/neu gene was amplified in 37 (10%) out of 379 ER positive cases and in 39 (28%) out of 139 ER negative cases. Her-2/neu was amplified in 22 (7%) out of 301 PR positive cases and in 54 (25%) out of 217 PR negative cases. Amplification occurred in 18 (8%) out of 222 negative MIB-1 cases and amplified in 58 (20%) out of 296 positive cases. Amplification was seen in 5 (10%) out of 49 grade I tumors, 17 (12%) out of 143 grade II tumors and 54 (27%) out of 198 grade III tumors. Lobular carcinomas were not graded. Amplification was present in 52 (15%) out of 346 T1 lesions, in 17 (13%) out of 130 T2 lesions, in 5 (17%) out of 30 T3 lesions and in 2 (17%) out of 12 T4 lesions. Her-2/neu was amplified in 67 (14%) out of 467 woman 41 years and older, and in 9 (18%) out of 51 women 40 years and younger. Comparison of these frequencies using chi-square test revealed statistically significant correlation between Her-2/neu amplification and ductal versus lobular carcinoma (p<0.0003), ER (p=0.0001) and PR (p<0.0001) negative tumors, over-expression of MIB-1 (p<0.0005) and high tumor grade (p=0.0009), while size of the tumor (p=0.08) and age of the patients (p=0.67) were not statistically significant. Correlation was found between Her-2/neu amplification and tumor type, high histological grade, ER and PR negative tumors, and high proliferative MIB-1 index. No correlation was found between size of the tumor and age of the patient with Her-2/neu amplification.     

The Singaporean response to the SARS outbreak: knowledge sufficiency versus public trust

During the outbreak of severe acute respiratory syndrome (SARS) in Singapore from 1 March to 11 May 2003, various national prevention and control measures were undertaken to control and eliminate the transmission of the infection. During the initial period of the epidemic, public communication was effected through press releases and media coverage of the epidemic. About a month into the epidemic, a public education campaign was mounted to educate Singaporeans on SARS and adoption of appropriate behaviours to prevent the spread of the disease. A survey was conducted in late April 2003 to assess Singaporeans' knowledge about SARS and infection control measures, and their concerns and anxiety in relation to the outbreak. The survey also sought to assess their confidence in the ability of various institutions to deal with SARS and their opinion on the seemingly tough measures enforced. The study involved 853 adults selected from a telephone-sampling frame. Stratified sampling was used to ensure adequate representation from major ethnic groups and age groups. The study showed that the overall knowledge about SARS and control measures undertaken was low (mean per cent score of 24.5 +/- 8.9%). While 82% of respondents expressed confidence in measures undertaken by Tan Tock Seng Hospital (the hospital designated to manage SARS), only 36% had confidence in nursing homes. However, >80% of the public agreed that the preventive and control measures instituted were appropriate. Despite the low knowledge score, the overall mean satisfaction score of the government's response to SARS was 4.47 (out of possible highest score of 5.00), with >93% of adult Singaporeans indicating that they were satisfied or very satisfied with the government's response to SARS. Generally, Singaporeans had a high level of public trust (satisfaction with government, confidence in institutions, deeming government measures appropriate), scoring 11.4 out of possible maximum of 14. The disparity between low knowledge on the one hand and high confidence and trust in the actions of the government on the other suggests that Singaporeans do not require high knowledge sufficiency to be confident in measures undertaken by the government to control the SARS crisis.     

Bullying perspectives: experiences, attitudes, and recommendations of 9- to 13-year-olds attending health education centers in the United States

Because 1 in 5 elementary school and 1 in 10 middle school students in the United States report being bullied, understanding student perspectives is crucial to prevention. This study solicited opinions of 9- to 13-year-olds regarding the magnitude of, causes of, and remedies for bullying. Data were obtained from 1229 students visiting 11 health education centers in seven states. Students responded via anonymous, electronic keypads. Half the respondents said they have been bullied at least once in a while. When bullied, almost half said they fight back, about a fourth tell an adult, and 20% do nothing; only 8% try to talk to the bully. Nearly two thirds claimed they tell or try to stop bullying when they see it, but 16% do nothing, and 20% join in. Almost three fourths believed bullying is "uncool," yet 42% said they bully at least occasionally. Bullies and victims were more likely to be middle school age. Frequent bullies were more likely to think it is cool, to fight back when bullied, and to join in when others are bullied. Two classes of victims were apparent. Victims who also bully often said that bullying occurs because others are not friendly to bullies or because bullies want to get their way; many also admitted that they do not know how it can be stopped. Victims who do not bully were most likely to do nothing when bullied but to try to stop the bullying of others. Recommendations are given for using these findings to customize curricula or programs.     

Epidemiology of sepsis in Victoria, Australia

OBJECTIVE: To determine the clinical and epidemiologic characteristics of patients with sepsis admitted to hospitals in Victoria, Australia, including the incidence of sepsis and severe sepsis, utilization of intensive care unit (ICU) resources, and hospital mortality. DESIGN: A population-based hospital morbidity database generated from hospital discharge coding. SETTING: State of Victoria, Australia (population, 4.5 million), the 4-yr period from July 1, 1999, to June 30, 2003. PATIENTS: A total of 3,122,515 overnight hospitalizations. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The overall hospital incidence of sepsis was 1.1%, with a mortality of 18.4%. Of septic patients, 23.8% received some care in an ICU. For these patients, hospital mortality was 28.9%. Severe sepsis, defined by sepsis and at least one organ dysfunction, occurred in 39% of sepsis patients and was accompanied by a hospital mortality of 31.1%. Fifty percent of patients with severe sepsis received at least some care in an ICU. CONCLUSIONS: Australian state hospital administrative data reveal epidemiologic features of sepsis and severe sepsis that are strikingly similar to those recently reported from comparable populations in North American and Europe. This suggests that lessons learned in this area may be directly applicable internationally.     

Patterns and outcomes of chemotherapy for elderly patients with stage II ovarian cancer: a population-based study

BACKGROUND: The optimal treatment for patients with stage II ovarian cancer is controversial, although most experts recommend adjuvant chemotherapy. The purpose of this study was to assess the patterns of use of chemotherapy in women with stage II ovarian cancer, and to compare the survival of treated and untreated patients aged 65+ years in a population-based sample. METHODS: Using the Surveillance, Epidemiology, and End Results (SEER)-Medicare database of cancers diagnosed in approximately 14% of the U.S. population, we identified women who were diagnosed with stage II ovarian cancer between 1992 and 1996, survived >or=120 days beyond diagnosis, and were >or=65 years of age. Multivariate regression was used to compare those treated to those not treated with chemotherapy. Cox proportional hazards regression models were used to analyze patient survival. RESULTS: Of 236 women with stage II ovarian cancer, 160 (67.8%) received chemotherapy, and 118 (50%) received platinum-based regimens. Younger patients and those with higher-grade tumors were more likely to receive chemotherapy. The adjusted hazards ratio for mortality associated with any chemotherapy use was 0.67 (95% CI, 0.45-0.98), corresponding to an increase in median survival from 28 months to 35 months (P < 0.0001). CONCLUSIONS: This observational study found that most patients aged >or=65 years and diagnosed with stage II ovarian cancer between 1992 and 1996 were treated with chemotherapy. Grade and younger age were the most significant predictors of treatment, and treatment was associated with a 5-year mortality reduction of 33%. These findings are not definitive, but they may provide some guidance in the absence of randomized trials of adjuvant chemotherapy for older women with stage II ovarian cancer.     

Effectiveness of platinum-based chemotherapy among elderly patients with advanced ovarian cancer

BACKGROUND: Platinum-based chemotherapy is the standard of care for women with advanced ovarian cancer based on the results of randomized trials. We previously showed that only about half of women over the age of 65 years with this disease received platinum-based chemotherapy, and that the likelihood of receiving it decreases with age. METHODS: We used the Surveillance, Epidemiology, and End Results (SEER)-Medicare database to identify women diagnosed from 1/1/92 to 12/31/96 with stage III or IV ovarian cancer who survived > or =120 days beyond diagnosis, and were > or =65 years of age. Cox proportional hazards models and propensity scores were used to control for known predictors of receiving treatment and to estimate the relative effectiveness of different platinum-based regimens. RESULTS: Of the 1759 patients in the sample who met our eligibility criteria, 53% received platinum-based therapy. For this sample, the Cox proportional hazard ratio was 0.72 (95% CI, 0.62-0.91) for mortality associated with the use of any platinum-based therapy, and 0.59 (95% CI, 0.45-0.76) for combination platinum/paclitaxel therapy. Similar results were obtained using propensity score modeling. CONCLUSIONS: In this population-based study, we found that only about half of women with advanced ovarian cancer over age 65 were treated with platinum-based chemotherapy; however, survival improved by 38% in treated women, similar to the benefits described in randomized controlled trials among younger patients, and were greatest when platinum was combined with paclitaxel. An effort to increase the utilization of platinum combination therapy among older patients with advanced ovarian cancer is justified.