In VivoStudies of Adenovirus-Based p53 Gene Therapy for Ovarian Cancer

Objectives.To test the safety, efficacy, and toxicity of gene therapy using wild-type p53-expressing adenovirus (Ad-CMV-p53) in a nude mouse model with intraperitoneal (ip) 2774 human ovarian cancer cell line that contains a p53 mutation.Study design.An initial study of adenovirus tolerance was determined in nude mice by a single ip injection of increasing doses of Ad-CMV-p53. Nude mice were implanted with an LD₁₀₀dose of 1 × 10⁷cells. To study the efficacy and specificity of Ad-CMV-p53 treatment, the mice received treatment with different adenovirus constructs. One group received Ad-CMV-p53 and another group received a control adenovirus construct, Ad-CMV-βgal. To study the treatment response to Ad-CMV-p53, the mice were divided into groups and received various treatment schedules of 1 × 10⁸pfu of Ad-CMV-p53.Results.The mice tolerated Ad-CMV-p53 without adverse effects at doses of 1 × 10⁸pfu. The response to Ad-CMV-p53 showed significant survival duration in each dose regimen, with a survival time greater than that of untreated animals (P= 0.0173). However, no statistically significant survival advantage was observed between Ad-CMV-p53- and Ad-CMV-βgal-treated mice.Conclusions.These studies show that at the adenovirus dose and administration regimen used, there is effective but not specific 2774 tumor growth inhibitionin vivo.Efficient introduction of biologically active genes into tumor cells would greatly facilitate cancer therapy. Thus, although promising, these results caution that much effort will be required to realize the potential for clinical application of adenovirus-based ovarian cancer gene therapy.     

Accuracy of women's recall of opportunistic recruitment for cervical cancer screening in general practice

Abstract: Evaluation of strategies to improve opportunistic recruitment via general practice of women overdue for a cervical smear requires an accurate behavioural measure. As part of an experimental trial to evaluate the effect of a postgraduate workshop on preventive care, we conducted this methodological study to determine the accuracy of women's recall of an opportunistic discussion about cervical screening, by comparing it against audiotapes ( n = 524). Taking the taped evidence of the trainee's verbal behaviour as the gold standard, sensitivity was 85 per cent (95 per cent confidence interval (CI) 73.1 to 92.0 per cent) and specificity was 78 per cent (CI 73.9 to 81.6 per cent). Given the low rate of opportunistic recruitment by trainees in the main study, only one–third of positive recollections by women of an opportunistic discussion about cervical screening were correct. Until other measures have been validated, women's recall may continue to be used to measure general practitioners' behaviour, but an appreciation of likely bias is recommended.     

The effect of contrast dose,imaging time,and lesion size in the MR detection of intracerebral metastasis.

PURPOSETo evaluate the effect of MR contrast dose versus delayed imaging time on the detection of metastatic brain lesions based on lesion size.METHODSContrast MR examinations with gadoteridol were obtained in 45 patients with brain metastases. The patients were divided into two groups: 16 received cumulative standard dose (0.1 mmol/kg) and 29 received cumulative triple dose (0.3 mmol/kg). Both groups were evaluated at two dose levels (lower dose and higher dose) with two separate injections. Each patient received an initial bolus injection of either 0.05 (cumulative standard dose) or 0.1 (cumulative triple dose) mmol/kg of gadoteridol to reach the lower-dose level and underwent imaging immediately and 10 and 20 minutes later. Thirty minutes after injection, an additional bolus injection of 0.05 (cumulative standard dose) or 0.2 (cumulative triple dose) mmol/kg was administered to reach the cumulative higher-dose level (cumulative standard dose, 0.1 mmol/kg; cumulative triple dose, 0.3 mmol). Images were acquired immediately.RESULTSThere was no difference in the detection rate for lesions larger than 10 mm among T2-weighted, lower-dose immediate and delayed, or immediate higher-dose images in both study groups. Lesions smaller than 10 mm had improved detection with delayed imaging in both study groups; however, the immediate higher-dose studies still had the highest detection rate.CONCLUSIONIn the evaluation of small central nervous system metastases, either delayed imaging after the injection of standard contrast dose or higher contrast dose may improve their detection, and therefore affect clinical management. Higher contrast dose (cumulative triple dose) studies appear to be more effective than delayed imaging with standard dose.     

Articulation of Asthma and Its Care Among Low-Income Emergency Care Recipients

Low-income minority patients from East St. Louis, Illinois, a depressed midwestern urban city, who had visited acute care settings with asthma symptoms, participated in a focus group. Questions were constructed around the Health Belief Model to characterize participants' experiences in receiving asthma care, their confidence in long-term asthma self-management, barriers they perceived to managing their asthma, and recommendations they would make for improving asthma care in their community. Analysis of comments suggests an appreciable understanding of asthma triggers, limited coping behaviors for asthma symptoms, very limited practice of active asthma management, perception of the health care system as frequently insensitive to their needs or their knowledge of their own care, exchange of well-articulated information regarding how to deal with the system, and an apparent lack of awareness of any potential contribution of patient education or support system.     

Neutrophil Bactericidal Function in Diabetes Mellitus: Evidence for Association with Blood Glucose Control

Neutrophil bactericidal activity was assessed in patients with type 1 (n=45) and Type 2 diabetes mellitus (n=68) and non-diabetic control subjects (n=40) by measurement of whole blood chemiluminescence. Though chemiluminescence values tended to be highest in the non-diabetic subjects these differences were not statistically significant (mean ± SD) (2.73 ± 1.65 mV (controls), 2.33 ± 1.41 mV (Type 1 diabetes) and 2.38 ± 1.12 mV (Type 2 diabetes), F=1.12, p=0.33). Significant negative correlations were evident, however, in patients with both Type 1 and Type 2 diabetes between chemiluminescence and glycated haemoglobin (r_s=-0.35, p=0.005 (Type 1), r_s=-0.45, p=0.002 (Type 2), fructosamine (r_s=-0.36, p=0.003 (Type 1), r_s=-0.42, p=0.004 (Type 2)), and random blood glucose (r_s=-0.25, p=0.04 (Type 1), r_s=-0.48, p=0.001 (Type 2)). Changes in whole blood chemiluminescence in a further group of 10 patients with Type 2 diabetes mellitus commenced on insulin therapy were followed for 21 days. Serum fructosamine concentrations fell significantly over this time (524 ± 58 μmol l^?1 to 405 ± 47 μmol l^?1, p<0.001), however, although chemiluminescence values tended to rise these changes were not statistically significant (1.01 ± 0.38 mV to 1.60 ± 0.91 mV, S=4.24, df=5, p=0.52). These results suggest that impaired neutrophil bactericidal function is associated with poor blood glucose control. While it is likely that neutrophil bactericidal function will improve as blood glucose control improves, further studies are required both to confirm this and to demonstrate a reduction in the incidence of clinical bacterial infection.     

The role of general hospitals in the privatization of inpatient treatment for serious mental illness.

For almost three decades, many have regarded general hospital psychiatric units as the most appropriate setting for acute treatment of persons with serious mental illness who were once treated mostly in state hospitals. The extent to which this transfer has taken place and the differences between public and private general hospitals have been unclear. Using data from the 1988 National Mental Health Facilities Study and published data from the 1970s, the authors found that nearly half of all general hospitals providing psychiatric services treat persons with serious mental illness. Significant differences in case and payer mix were observed between public and private general hospitals, although these differences were smaller than in the 1970s. The findings suggest increased involvement by private general hospitals in treating patients reimbursed by public payers, but the findings also indicate that persons with serious mental illness and those using Medicaid are still more prevalent in public general hospitals than in private ones.     

Meeting health care needs of women experiencing complications of miscarriage and unsafe abortion: USAID's postabortion care program

Each year, an estimated 210 million women become pregnant. Worldwide, more than one fourth of these pregnancies will end in abortion or an unplanned birth. While many abortions may result from the desire to delay or avoid pregnancy, 15% to 20% of pregnancies will end in miscarriage or stillbirth with some causative agents being malaria, HIV/AIDS, and physical violence. Postabortion care (PAC) is needed to provide treatment for complications caused by incomplete or spontaneous abortion and critical family planning counseling and services to prevent future unplanned pregnancies that may result in repeat abortions. In 2003, the United States Agency for International Development (USAID) initiated a 5-year strategy wherein seven countries were provided financial funding and technical assistance. Since 2003, more than 3000 women have been seen in health centers and health posts for PAC services; more than 14,000 community members have received messages on unsafe abortion; family planning, and complications of unsafe abortion and miscarriage; and more than 600 documents were reviewed for inclusion in a global PAC resource package. This package has been used for developing Cambodia's national PAC policy and for developing patient education materials and provider job aids in Cambodia and Tanzania. These promising methodologies will be replicated in other countries.