Effects of neuropeptide Y on food-reinforced behavior in satiated rats.

The effect of NPY on behavior and food intake of food-satiated rats was examined under three different food availability conditions. Food was available during times when rats normally do not eat under either a fixed-ratio or fixed-interval reinforcement schedule, or it was freely available in the bottom of the cage (FF). Forty responses were required for each 45-mg food pellet under the ratio schedule (FR 40) and for the first response to occur 15 s after the previous reinforcement under the interval schedule (FI 15"). NPY (5 micrograms) significantly increased food intake under all conditions and increased food-reinforced responses under the FR and FI schedules. NPY's effect on food intake was greatest when food was freely available and least for rats working under the schedule requiring the most effort (FR 40). Food intake peaked after 3 days under repeated daily administration of NPY. Under free food access and under the fixed-interval schedule, eating and/or responding occurred almost immediately following the onset of the initial 4-h session under NPY. However, during the first session following NPY administration under the FR, rats emitted few responses during the first 2 h of the session. The onset of robust responding under the FR schedule began earlier with each successive daily administration of NPY. These data show NPY substantially increases food-maintained behavior and is a potent inducer of food intake even under conditions where considerable effort is required to obtain food. Further, the conditions under which food is made available can dramatically alter NPY's effect on the temporal pattern of food-maintained responding, feeding, and latency to eat.     

Factors affecting the availability and use of hemodialysis facilities

This article describes factors related to the geographic distribution of hemodialysis facilities and the relationship between availability and use. Such facilities tend to be concentrated in the same types of areas as other medical resources, and the number of medical specialists in an area is related to the rate of treatment for renal diseases. The proportion of treatment stations in an area owned by for-profit organizations is not related to the total treatment rate, but the market share of for-profit facilities is positively related to in-center treatment and negatively related to home treatment.     

Overexpression of oncogenic STK15/BTAK/Aurora A kinase in human pancreatic cancer.

PURPOSE: Multiple chromosome abnormalities, including gain of chromosome20q, have been detected frequently in human pancreatic cancers. Overexpression of the STK15/BTAK/Aurora A gene located on chromosome 20q13, which encodes a centrosome-associated serine/threonine kinase, has been shown to induce chromosomal instability, leading to aneuploidy and cell transformation in multiple in vitro experimental systems. The purpose of this study was to investigate the expression and copy number alteration of STK15 in pancreatic cancer. EXPERIMENTAL DESIGN: STK15 expression at both the mRNA and protein levels together with the copy number of STK15 gene was measured in nine pancreatic carcinoma cell lines: (a) HPAF-II; (b) Aspc-1; (c) Panc-1; (d) Panc-3; (e) Panc-28; (f) Panc-48; (g) HS766T; (h) MIAPaCa-2; and (i) BxPc3. STK15 protein expression was also examined in normal pancreatic tissues and tumors by Western blotting and immunohistochemistry. RESULTS: STK15 was overexpressed in all of the nine cell lines examined, but gene amplification was infrequent. Western Blot analysis of primary tumor tissues revealed 2-10 times overexpression of STK15 protein compared with normal adjacent tissues from pancreatic cancer patients. Concurrent overexpression of cdc20, an STK15-associated protein, and reduced expression of cdc25, a mitosis-activating protein phosphatase, were detected in the same tumor samples. Elevated STK15 protein expression was detected in 22 of 38 tumor sections (58%) from pancreatic cancer patients. The extent of STK15 expression was not significantly correlated with the size, degree of differentiation, and metastasis status of the tumors. CONCLUSIONS: These results show that STK15 is overexpressed in pancreatic tumors and carcinoma cell lines and suggest that overexpression of STK15 may play a role in pancreatic carcinogenesis.     

A phase I study of 5-fluorouracil, leucovorin and levamisole

 Purpose: The activity of 5-fluorouracil (5-FU) against colon cancer is enhanced by leucovorin and the combination of 5-FU and levamisole has activity in the adjuvant treatment of colonic malignancies. The combination of 5-FU with both leucovorin and levamisole may provide additional benefit in the treatment of colon cancer. Methods: A phase I study to assess qualitative and quantitative toxicities of this three-drug combination and to determine a dose for further phase II testing was undertaken. The role of levamisole as an immunomodulator was also assessed. Results: A group of 38 patients with incurable etastatic malignancies received 119 cycles of treatment at eight dose levels. 5-FU (375 mg/m² per day) and leucovorin (200 mg/m² per day) were administered intravenously (days 1–5). Levamisole was administered orally (days 1–3 and 15–17) at doses from 30 to 470 mg/m² per day. Patients received both 5FU/leucovorin and 5-FU/leucovorin/levamisole in random order for their initial two cycles. All subsequent treatments were with the three-drug combination. Toxicities included nausea, vomiting, stomatitis, thrombocytopenia and granulocytopenia. Diarrhea was the dose-limiting toxicity at 470 mg/m² per day levamisole. The addition of levamisole resulted in more toxicity than 5-FU and leucovorin alone. No clinical responses were seen with this regimen. The addition of levamisole resulted in more immunomodulation than 5-FU and leucovorin alone as evidenced by release of neopterin from monocytes. Conclusion: With this schedule and dose of 5-FU and leucovorin, the maximum tolerated dose of levamisole was 354 mg/m². However, given the lack of response and the absence of dose-dependent immunomodulation, this may not be the appropriate dose for further phase 11 studies. Received: 20 October 1995 / Accepted: 16 June 1996     

Treatment options for perianal Bowen's disease: survery of American Society of Colon and Rectal Surgeons Members

The aim of this study was to determine current management practices of physicians caring for patients with perianal Bowen's disease. A questionnaire was sent to 1,499 members listed in the 1997 American Society of Colon and Rectal Surgeons Directory asking them how many patients they have treated and which operative or nonoperative treatment option they choose for small (< or =3 cm), large (> 3 cm), and microscopic lesions. Of 1,499, 663 (44.2%) surgeons responded. Not all respondents answered each item. Seventy-five per cent of surgeons surveyed (n = 653) devote greater than 75 per cent of their practice to colon and rectal surgery. Of 642 respondents, 552 (86%) managed a total of <10 patients, and 90/642 (14%), > or =10 patients. Ninety-six per cent of respondents use wide local excision for patients with small lesions. Eighty-seven per cent of respondents use wide local excision for patients with large lesions. Seventy-four per cent treat patients with microscopic disease conservatively and without wide excision. The majority of surgeons caring for patients with perianal Bowen's disease are performing wide local excision for both small and large lesions. Microscopic disease was usually treated conservatively with observation alone.     

Two BRM promoter polymorphisms predict poor survival in patients with hepatocellular carcinoma

Polymorphisms in the promoter of the BRM gene, a critical subunit of the chromatin remodeling SWI/SNF complex, have previously been implicated in risk and prognosis in Caucasian‐predominant lung, head and neck, esophageal, and pancreatic cancers, and in hepatocellular cancers in Asians. We investigated the role of these polymorphisms in hepatocellular carcinoma (HCC) risk and prognosis. HCC cases were recruited in a comprehensive cancer center while the matched controls were recruited from family practice units from the same catchment area. For risk analyses, unconditional logistic regression analyses were performed in HCC patients and matched healthy controls. Overall survival analyses were performed using Cox proportional hazard models, Kaplan‐Meier curves, and log‐rank tests. In 266 HCC cases and 536 controls, no association between either BRM promoter polymorphism (BRM‐741 or BRM‐1321) and risk of HCC was identified (P > 0.10 for all comparisons). There was significant worsening of overall survival as the number of variant alleles increased: BRM‐741 per variant allele adjusted hazards ratio (aHR) 5.77, 95% confidence interval (CI) 2.89‐11.54 and BRM‐1321 per variant allele aHR 4.09, 95%CI 2.22‐7.51. The effects of these two polymorphisms were at least additive, where individuals who were double homozygotes for the variant alleles had a 45‐fold increase in risk of death when compared to those who were double wild‐type for the two polymorphisms. Two BRM promoter polymorphisms were strongly associated with HCC prognosis but were not associated with increased HCC susceptibility. The association was strongest in double homozygotes for the allele variants.     

Does a Low Glycaemic Index (GI) Diet Cost More during Pregnancy?

The aim of this study was to examine the monetary cost of dietary change among pregnant women before and after receiving low glycaemic index (GI) dietary advice. The pregnant women in this study were a subgroup of participants in the Pregnancy and Glycaemic Index Outcomes (PREGGIO) study. Twenty women from the low GI dietary advice group, who had completed their pregnancies, were randomly chosen. All these women had completed three day food records at 12–16 weeks and again around 36 weeks of gestation. Consumer food prices were applied to recorded dietary intake data. The mean ± SD GI of the diet reduced from 55.1 ± 4.3 to 51.6 ± 3.9 (p = 0.003). The daily cost of the diet (AUD) was 9.1 ± 2.7 at enrolment and 9.5 ± 2.1 prior to delivery was not significantly different (p = 0.52). There were also no significant differences in the daily energy intake (p = 0.2) or the daily cost per MJ (p = 0.16). Women were able to follow low GI dietary advice during pregnancy with no significant increase in the daily costs.