Effects of weight cycling induced by diet cycling in rats differing in susceptibility to dietary obesity

OBJECTIVE: Although the majority of evidence in rodents does not support the view that weight cycling (consisting of bouts of food restriction and refeeding) promotes obesity, the effects of weight cycling on body weight regulation remain controversial. We have previously demonstrated that some rats within a strain are more susceptible to develop obesity than others when given free access to a high-fat diet. In this study, we tested the hypothesis that rats most susceptible to weight gain on a high-fat diet would also be most susceptible to weight gain as a consequence of weight cycling. RESEARCH METHODS AND PROCEDURES: Rats were provided a low-fat diet (12% corn oil) for 2 weeks, then given a high-fat diet (45% corn oil) for 2 weeks to identify those most (obesity prone) and least (obesity resistant) susceptible to weight gain. Half of each group was then subjected to three 30-day cycles of food restriction (10 days) and refeeding (20 days) [weight cycler (WC) rats]. The other half were allowed free access to the high-fat diet [control (CO) rats]. All rats were then followed for an additional 10 weeks, with free access to the high-fat diet. RESULTS: When considering the entire 160 days of the study, we found no evidence that WC rats relative to CO rats had increased body weight, increased body fat content, or elevated energy efficiency. We found no evidence that rats most prone to dietary obesity were also prone to weight gain after weight cycling. During the weight cycling phase (days 1 to 90), weight cycled groups consumed less energy and gained less weight than controls. During the follow-up phase, WC and CO rats did not differ significantly in weight gain or energy intake. DISCUSSION: In this study, weight cycling did not exacerbate the obesity produced by high-fat diet feeding.     

The write stuff: the Whitney Project

In 1993 Maria Mathes, a Pecos, New Mexico teacher, started an innovative educational program by using letter writing as part of the sixth-grade English curriculum. Mathes had her class write letters to people in the news. Based on a People magazine article, the class began writing to an 11-year-old Chicago girl living with AIDS, named Whitney Williams. This started a friendship and support system for children with HIV or AIDS, called the Whitney Project. During the school year, the class held fundraisers to allow Whitney and her family to visit, and she was treated to celebrations throughout the town. The program was expanded the following year, and continues, despite funding problems in the past. Through this program AIDS-affected children get the chance to express their feelings and students learn about HIV/AIDS. There is no cost to participate, and confidentiality can be protected. Contact information is provided, along with details for ordering a video describing the program.     

Expression of caspase-3 in brains from paediatric patients with HIV-1 encephalitis

Apoptosis of neurones, macrophages, and microglia occurs in the brains of paediatric patients with human immunodeficiency virus (HIV) type 1 encephalitis, which is often associated with pre-mortem neurological disease (progressive encephalopathy). We have previously reported that TUNEL-positive neurones in brain tissue from paediatric patients with HIV type 1 encephalitis and progressive encephalopathy are strikingly devoid of the pro-apoptotic gene product Bax, in marked contrast to brain-resident macrophages and microglia. Using immunocytochemical methods, the present study demonstrate that neurones in patients with HIV type 1 encephalitis and progressive encephalopathy, as well as macrophages and microglia, but not astrocytes, overexpress caspase-3, a pro-apoptotic enzyme that is proteolytically activated downstream of Bax-Bcl-2 dysregulation. Co-localization of neuronal cytoplasmic caspase-3 and nuclear TUNEL staining, a marker for fragmented DNA, was also infrequently observed in brain tissue from patients with HIV type 1 encephalitis and progressive encephalopathy. These findings suggest that vulnerable neurones in brain tissue from patients with HIV virus type 1 encephalitis and progressive encephalopathy undergo apoptosis by a mechanism that involves upregulation of caspase-3 in a pathway that is independent of Bax-Bcl-2 dysregulation. Furthermore, caspase-3 upregulation in apoptotic neurones likely occurs prior to DNA fragmentation.     

The management of women with breast symptoms referred to secondary care clinics in Sheffield: implications for improving local services

Information was collected about 302 women referred for breast symptoms and seen in surgical outpatient or outreach clinics during one month at two hospitals in Sheffield. Three-quarters of the women (n = 244) were referred to specialist breast clinics, 22% (n = 70) were referred to general surgical clinics and 3% (n = 6) were referred to outreach clinics. The ages of the women ranged from 16 to 85 years with a mean and median age of 45 years. Some 200 women (66%) presented with a lump or lumpiness, 42 women (14%) presented with pain, 29 women (10%) had a skin and/or nipple problem, and the remaining 31 women (10%) were concerned about their family history or reported other symptoms. A total of 23 women (8%) were diagnosed as having cancer, 180 (60%) were diagnosed as having benign breast disease, and 99 (33%) were diagnosed as normal. Of the 23 women with cancer, 22 were over 40 years of age; 21 women presented with a lump, one presented with pain, and one presented with metastatic disease. The time required to reach a final clinical diagnosis varied from the same day as the clinic visit to 35 weeks, with a median time of 3 weeks. Surgeons assessed the appropriateness of GPs' referrals for 257 cases and judged that 122 (47%) could have been managed by a GP. The implications of the findings for the organisation of specialist outpatient clinics are discussed, and a categorisation of women as either urgent or routine cases is suggested.     

Human phase I vaccine trials of 3 recombinant asexual stage malaria antigens with Montanide ISA720 adjuvant

Two phase I vaccine trials were conducted to test the immunogenicity and safety of a vaccine containing three recombinant malaria antigens from the asexual stage of Plasmodium falciparum. The three antigens are a fragment of MSP1 (190LCS.T3); MSP2 and a portion of RESA and were formulated in Montanide ISA720 adjuvant. These trials investigated the dose response of each antigen for eliciting both antibody and T-cell responses and the immunogenicity of a mixture of the antigens compared with the antigens injected separately. All three antigens elicited both antibody and T-cell responses. Strong T-cell responses were observed with 190LCS.T3 and RESA with stimulation indices exceeding 100 for peripheral blood leucocytes in some individuals. The antibody responses were generally weak. The human antibody responses observed with MSP2 in Montanide ISA720 were not significantly different from those obtained in an earlier trial which used MSP2 with alum as the adjuvant. No antigenic competition was observed: volunteers receiving a mixture of antigens had similar responses to those receiving the three antigens at separate sites. Tenderness and pain at the injection site were common over the first few days following immunization. In some volunteers, especially those receiving the highest doses tested, there was a delayed reaction at the injection site with pain and swelling occurring approximately 10 days after injection.     

Risk factors for mental disorder hospitalization after the Persian Gulf War: U.S. Armed Forces, June 1, 1991-September 30, 1993

Effects of Persian Gulf War (August 2, 1990–July 31, 1991) and Gulf War occupation on post-War hospitalization risk were evaluated through Cox proportional hazards modeling. Active-duty men (n = 1,775,236) and women (n = 209,760) in the Army, Air Force, Navy, and Marine Corps had 30,539 initial postwar hospitalizations for mental disorders between June 1, 1991 and September 30, 1993. Principal diagnoses in the Defense Manpower Data Center hospitalization database were grouped into 10 categories of ICD-9-CM codes. Gulf War service was associated with significantly greater risk for acute reactions to stress and lower risk for personality disorders and adjustment reactions among men. Personnel who served in ground war support occupations (men and women) were at greater risk for postwar drug-related disorders. Men who served in ground war combat occupations were at higher risk for alcohol-related disorders. Longitudinal studies of health, hospitalization, and exposure beginning at recruitment, are needed to better understand how exposure to combat affects the mental health of military personnel.     

Pharmacokinetics of cisplatin administered by continuous hyperthermic peritoneal perfusion (CHPP) to patients with peritoneal carcinomatosis

The pharmacokinetics of cisplatin administered by continuous hyperthermic peritoneal perfusion (CHPP) was characterized in patients with peritoneal carcinomatosis. Cisplatin was added into the perfusate with escalating doses from 100 mg/m2 to 400 mg/m2. The hyperthermic perfusion was maintained for 90 minutes with a flow rate of 1.5 L/min and a target peritoneal temperature of 42.5 degrees C after a tumor debulking procedure. Samples of both the perfusate and blood were obtained during the perfusion and 30 minutes after the perfusion. Cisplatin plasma and perfusate concentrations were determined by flameless atomic absorption spectrometry with a lower limit of detection of 2 ng/ml and a coefficient of variation (CV) < 10%. Fifty-six patients were enrolled in the study. The mean (+/- SD) percentage of cisplatin present in the perfusate at the completion of perfusion was 27.8% +/- 20% of the total dose. The maximum cisplatin concentrations in the perfusate were 10 times higher than those in plasma. The area under the concentration-time curve (AUC) of the perfusate was 13 times higher than the AUC of plasma. A two-compartment model with an additional peritoneal cavity compartment fits to the data best based on the Akaike information criterion. However, the interpatient variability was considerably high (CV < 100%). In conclusion, cisplatin administered by hyperthermic peritoneal perfusion resulted in a pharmacological advantage by obtaining higher and direct drug exposure to the tumor in the peritoneal cavity while limiting systemic absorption and toxicity. Using a complex two-compartment model, the authors were able to characterize the pharmacokinetics of cisplatin given intraperitoneally via this technique.