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Biomedical subjects

H Kashtan

Publications and source records attributed to H Kashtan.

At least 37 records · Page 2Linked to original sources

Octreotide ameliorates glucose intolerance following acute experimental pancreatitis.

The long-term effects of octreotide, the synthetic analog of the hormone somatostatin, on acute experimental pancreatitis were studied. Acute pancreatitis was induced in rats by intraparenchymal injections of 0.5 ml 5% or 10% sodium taurocholate. Octreotide (10 mg/kg/day, subcutaneously), or saline injections as controls, were started four hours later, and their effects were assessed 30, 60, and 90 days after the induction of pancreatitis. Neither intrapancreatic saline injections nor octreotide administration without the induction of pancreatitis caused any biochemical or histological abnormalities. Taurocholate-induced pancreatitis was followed by remarkable hyperglycemia, which was ameliorated by octreotide. Thirty days after induction of pancreatitis, glucose levels were 269+/-21 mg/100 ml and 153+/-17 mg/100 ml in the control and octreotide treated animals, respectively (P < 0.02). Octreotide administration was associated with increased pH values after 60 and 90 days (P < 0.05 for the 90 days group). The levels of hematocrit, calcium, and amylase were already within the normal ranges after 30 days and were unaffected by octreotide. There were no signs of chronic exocrine insufficiency and all the surviving rats gained weight during the follow-up. However, the relative weights of the pancreases of the octreotide-treated animals were higher than those of the controls 30 days after IOP. Histopathological evaluation demonstrated regeneration of the pancreatic tissue, and increased number and hypertrophy of the islets of Langherhans. There were no significant differences whether the octreotide treatment was given for only 48 or 96 hr. Survival was significantly improved by octreotide; only one octreotide-treated rat (2.5%) with 10% taurocholate-induced pancreatitis died, while six (15%) of the control animals succumbed (P < 0.05). These studies provided data on the sequelae of acute pancreatitis and showed that octreotide may have long-term beneficial effects in this disease.

Acute Disease↗

[Diverticular disease of the appendix].

The incidence of appendiceal diverticulosis in pathologic specimens is 0.004-2.1%. Diverticular disease of the appendix is classified as congenital (true) or acquired (false). The clinical presentation differs from that of acute appendicitis. The average age is older, the pain is often intermittent, and while localized in the right lower abdominal quadrant, is of longer duration. No further treatment besides appendectomy is needed. Since a high rate of perforations, peritonitis and lower gastrointestinal bleeding have been reported as complications, it is recommended that in those with an incidental finding of diverticula of the appendix during surgery, that appendectomy be performed. It is not recommended to perform prophylactic appendectomy when diverticula of the appendix are found on barium enema.

Appendectomy↗

Survival of colorectal carcinoma in the elderly. A prospective study of colorectal carcinoma and a five-year follow-up.

PURPOSE: Colorectal carcinoma in elderly patients has become a more common problem in the last decade. There are some physicians who tend to offer a less definitive treatment for these patients because of their chronologic age. The purpose of this study was to evaluate the long-term survival of elderly patients (> 70) who underwent surgery for colorectal carcinoma in comparison with a younger group of patients with the same disease. METHODS: Long-term survival of patients with colorectal carcinoma who underwent surgery was prospectively evaluated. Long-term survival was compared between an elderly group of patients (age, > 70) and a younger group of patients. RESULTS: There was no significant difference in the five-year survival between the two age groups. Patients' survival was influenced by stage of the disease and type of operation (emergency vs. elective). CONCLUSIONS: Treatment decisions in elderly patients with colorectal carcinoma should not be influenced by the chronologic age of the patient.

Aged↗

Photodynamic therapy of colorectal cancer using a new light source: from in vitro studies to a patient treatment.

PURPOSE: Photodynamic therapy (PDT) is a relatively new alternative modality for palliation of rectal cancer. Current source of light for PDT are laser systems that are expensive and not necessarily needed for PDT. We evaluated a new nonlaser light source for PDT, Versa-Light. METHODS AND RESULTS: In vitro PDT--CT26 murine colon carcinoma cells were incubated with aluminum phthalocyanine (AlPcS4) for 48 hours and subjected to photoradiation using Versa-Light, and viability was assessed. There was a significant decrease in viability of treated cells compared with controls. In vivo PDT--BALB/c mice were injected either subcutaneously or intrarectally with CT26 cancer cells. IP AlPcS4 (2.5 mg/kg) was injected when tumors were visible. After 24 hours, mice were subjected to photoradiation. Massive tumor necrosis in response to PDT was observed. PDT also prolonged survival of treated mice. Patient treatment--A 70-year-old woman with recurrent local rectal carcinoma received intravenous Photofrin II (2 mg/kg). After 48 and 96 hours, she was subjected to direct photoradiation. After the first light session, there was complete macroscopic disappearance of the tumor. Biopsies up to 10 weeks after the treatment showed no cancer cells in the treated area. Sixteen weeks later, a randomized biopsy from previous tumor site showed carcinoma cells. CONCLUSIONS: We believe that Versa-Light, is a good light source for PDT. It was effective in both in vitro and animal studies. It can also be safely used for clinical PDT.

Aged↗

Differing proliferative responses in proximal and distal colons of growing rats fed food eaten by adenoma patients.

Animal dietary studies related to human colorectal carcinogenesis are usually based on AIN-76A diet, which is dissimilar to human food in source, preparation, and content. Our aim was to examine colonic epithelial proliferation in rats fed a diet based on the mean daily food intake of adenoma patients. Foods were prepared as reported by the adenoma patients and dehydrated; 64 Sprague-Dawley rats were fed either "human adenoma" or AIN-76A diet and every eight weeks, eight from each group were sacrificed. Both groups gained weight equally, had no colonic histological changes, but during the study showed progressive lengthening of colonic crypts (P < 0.01) and decreased proliferation (P < 0.05) in distal colons. Compared to controls, rats fed human adenoma diet had significantly longer crypts (P < 0.01) and more labeled cells (P < 0.05) at 32 weeks; overall they had increased proliferation (P < 0.01), most significantly in the distal colon. Thus, food eaten by adenoma patients induced hyperproliferative changes in the rat colon during growth and maturity, especially the distal colon, as found in humans at risk for neoplasia.

Adenoma↗

Inhibition of CT-26 murine adenocarcinoma growth in the rectum of mice treated with recombinant human interleukin-6.

In the present study we evaluated the antitumor effects of recombinant human interleukin-6 (rhIL-6), expressed in Chinese hamster ovary cells, in a murine primary tumor model. We showed that treatment with rhIL-6 substantially inhibited the implantation and growth rates of CT-26 adenocarcinoma tumor cells in the rectal submucosa of syngeneic mice. This effect was achieved by injecting rhIL-6 for 7 consecutive days starting 1 day prior to tumor inoculation. No obvious antitumor effect was noted when rhIL-6 injections started 5 days after tumor inoculation. Analysis of the mechanisms by which rhIL-6 exerts its antitumor effects did not reveal a direct antitumor effect on CT-26 tumor cells or the up-regulation of major histocompatibility complex antigens on these cells. However, infiltration of lymphocytes at the tumor site was observed. Increase of carcinoembryonic antigen by IL-6 was clearly seen in human HT-29 colon carcinoma cells. The possible application of these results for adjuvant immunotherapy of selected colorectal patients and prevention of reimplantation of tumor cells disseminated during surgery is discussed.

Adenocarcinoma↗

Antitumor effects of recombinant interleukin-6 expressed in eukaryotic cells.

In the present study we evaluate the antitumor efficacy of a glycosylated molecule of interleukin-6 (IL-6), which was cloned and expressed in Chinese hamster ovary cells. When tested with two syngeneic murine tumors, the MC38 adenocarcinoma and the MCA106 fibrosarcoma, recombinant IL-6 (rIL-6) significantly reduced the number of day-3 established MC38 lung metastases, but had no effect on MCA106 lung metastases. A similar effect of rIL-6 was seen on day-3 MC38 liver metastases. The antitumor activity mediated by rIL-6 was achieved at doses of the cytokine ranging from 6 micrograms to 150 micrograms/day. There was no correlation between the responsiveness to rIL-6 of these two tumors and their susceptibility, in vitro, to a direct cytostatic effect of the cytokine or the increase in the expression of major histocompatibility complex (MHC) antigens after exposure to rIL-6. However, a correlation was seen between the antitumor response to rIL-6 and the initial number of tumor cells expressing MHC antigens. The possible role of MHC antigens expressed on tumor cells, the generation of MHC-restricted cytotoxic cells and the responsiveness to IL-6 are discussed.

Animals↗

The apolipoprotein E gene and the serum low-density lipoprotein cholesterol response to dietary fiber.

Our goal was to determine whether differences in apolipoprotein E (apo E) influenced the response to dietary changes aimed at reducing serum cholesterol levels, especially increases in fiber. Apo E phenotype and genotype were determined in 43 men and 24 women who had previously taken part in parallel 2-week metabolic dietary studies involving either wheat bran or oat bran supplementation at a level of 6.8 g fiber/1,000 kcal. Fasting blood lipid measurements had been made at the beginning and end of the 2-week metabolic period. Reductions in low-density lipoprotein (LDL) cholesterol levels across both oat and wheat bran diets were significantly different depending on the E allele (P = .048). The LDL cholesterol level reduction for E2 carriers (0.60 +/- 0.14 mmol/L, n = 13) was greater than that for E3 homozygotes (0.21 +/- 0.07 mmol/L, n = 38; P = .014) and E4 carriers (0.28 +/- 0.12 mmol/L, n = 16; P = .09). Only the change in dietary fiber on the oat bran diet was related significantly to the decrease in LDL cholesterol levels (r = -.47, P = .007; n = 32). No such relationship was seen on the wheat bran diet (r = -.010, P = .59; n = 33). Carriers of the E2 allele appear to be more responsive than noncarriers to a dietary change involving increased fiber intake. The data also support a lipid-lowering advantage of oat bran over wheat bran. Current dietary recommendations to reduce serum lipid levels may vary in effectiveness depending on distribution of apo E alleles in the different populations studied.

Adult↗

Genetic variation associated with differences in the response of plasma apolipoprotein B levels to dietary fibre.

1. We hypothesized that differences within genes whose protein products are involved in apolipoprotein B metabolism could influence the response of plasma apolipoprotein B-containing lipoprotein concentrations to increases in dietary fibre. 2. We studied 67 subjects (43 men and 24 women) who had taken part in parallel 2 week metabolic dietary studies involving either wheat bran or oat bran supplementation. Fasting blood lipid, lipoprotein and apolipoprotein concentrations were measured at the start and end of the 2 week metabolic period. Genotypes were determined using DNA markers for the low-density lipoprotein receptor, apolipoprotein B, apolipoprotein CIII and hepatic lipase gene loci. 3. Reductions in plasma concentrations of apolipoprotein B were significantly different depending on genotype determined with a low-density lipoprotein receptor DNA marker (P = 0.03). There was no significant variation in the reduction of plasma total cholesterol, low-density lipoprotein cholesterol or apolipoprotein B concentrations for alleles of other genes tested. 4. Thus, genetic variability is associated with interindividual differences in the fibre-related reduction in plasma apolipoprotein B and apolipoprotein B-containing lipoprotein concentrations. Implementation of current dietary recommendations to reduce plasma lipoprotein levels with fibre may have variable effects in different individuals in part because of structural differences in candidate genes whose products are involved in lipoprotein metabolism.

Apolipoproteins B↗

The use of lasers in colorectal cancer.

The potential addition of lasers to the armamentarium of physicians treating advanced colorectal cancer is welcome because of the morbidity associated with the disease and because of the limitations of standard treatments for some of the problems related to this common disease. However, laser treatment cannot be regarded yet as a standard modality. Questions still remain regarding the efficacy of these treatments in relieving the most troublesome symptoms of tenesmus and urgency, although bleeding and mucous discharge appear to be well controlled. Additional questions remain regarding expense and the relative benefits of lasers versus electrocoagulation (much cheaper) for rectal cancers. Other concerns relate to the learning curve involved with lasers, particularly for decompression of colonic obstructions, and efficacy compared to pneumatic dilatation.

Colorectal Neoplasms↗

Colonic epithelial proliferation indices before and after colon cancer removal.

Rectal mucosal (epithelial) proliferation labeling indices (LI) have been widely used as a risk marker for colorectal cancer and as an intermediate end-point in chemoprevention studies. The purpose of this study was to determine whether the presence of cancer preoperatively altered the LI and whether these LI could be used over the long term as a marker for colon cancer. We studied 25 patients (18 with colorectal cancer and 7 with benign colonic diseases) who were admitted for colonic resection. Biopsies for thymidine LI were taken before, during, and 4 and 7 months after the operation. The preoperative LI of cancer patients was higher, but not significantly, than that of noncancer patients (5.22 +/- 3.54 and 4.11 +/- 1.34%, respectively, p = 0.28). The intraoperative LI was significantly higher than the preoperative LI (8.08 +/- 4.00 and 4.90 +/- 3.07%, respectively; p = 0.004). After 4 and 7 months, the LI was not significantly different from the preoperative LI (p = 0.60 and 0.89, respectively). Resection of a colonic segment did not affect the level of proliferation over time. Therefore, it is unlikely that LI can be used as a marker to predict local recurrence after curative resection of colorectal cancer.

Adult↗

The effect of lowering faecal pH on the rate of proliferation of the normal colonic mucosa.

Epidemiological and animal studies suggest that faecal pH may be a risk factor for colorectal cancer with low faecal pH associated with a lower incidence of the disease. The aim of this study was to determine whether faecal pH (or dietary fibre) affects the short-term risk factors for colon cancer. Sixty-nine normal volunteers were randomized into three equal groups (A-C). They provided food records, faecal specimens and submitted to rectal biopsy for thymidine labelling studies before and after a 2-week intervention. Group A received a placebo of fruit juice. Group B, approximately 3.0 g d-1 sodium sulphate in juice. Group C, 30 g d-1 supplementary dietary fibre as wheat bran in bread. Age, sex, weight, height and intake of macronutrients and minerals were similar in the groups prior to intervention. Faecal pH was similar for the three groups before and was reduced in Group B after intervention (P = 0.001) with a relative reduction of 0.5 pH units. The labelling index for the three groups was similar prior to intervention; after, it was lowest in Group B with a relative reduction of 0.5% points, although this difference was not statistically significant. The results thus do not support the hypothesis that an acidification of faecal pH leads to a reduction in risk markers for colon cancer.

Adult↗

Intra-rectal injection of tumour cells: a novel animal model of rectal cancer.

The purpose of this study was to develop an animal model of rectal cancer. Three murine-derived cell lines, B16 melanoma, CT26 and MCA38 colon carcinoma, as well as the human colon cancer cell line LS174T were injected into the submucosa of the mouse rectum. Subcutaneous CT26 anbd B16 tumours and intra-caecal CT26 tumours served as controls for tumourigenicity of the cell lines. B16 melanoma produced a locally aggressive rectal tumour as well as skin and para-aortic lymph node metastases. CT26 produced local tumour when injected intra-rectally and colon tumours and liver metastases when injected into the caecum. MCA38 and LS174T intra-rectal injections resulted in large rectal carcinomas without metastases. We believe that growth of a colon cancer cell line in the rectum approximates the human disease more closely than other models of colorectal cancer. We would expect that the model could similarly be utilized to assess the effects of novel adjuvant treatments for rectal cancer as well as in the study of the tumour biology of rectal cancer.

Adenocarcinoma↗

Colonic fermentation and markers of colorectal-cancer risk.

The aim of this study was to determine the effect of soluble fiber on indexes of colon-cancer risk in postpolypectomy and nonpolyp patients. Forty-five postpolypectomy and 49 nonpolyp volunteers completed 2-wk metabolic studies where half of the group received oat-bran supplements and the other half took wheat-brain supplements. Colonic biopsies taken before and after the intervention showed no difference in the index of thymidine colonic-crypt-cell labeling, thymidine-labeling pattern, or nuclear aberrations. Nevertheless, fecal pH was significantly reduced by 0.23 +/- 0.07 pH units (P less than 0.002) as an index of increased colonic fermentation on oat bran. This was not associated with increased basal breath hydrogen concentrations; fecal butyrate concentrations were higher on wheat bran. We conclude that soluble fiber as oat brain appears to have no advantage over wheat bran in modifying putative risk factors for colonic cancer.

Butyrates↗

Wheat-bran and oat-bran supplements' effects on blood lipids and lipoproteins.

To compare the effects of oat-bran fiber on blood lipids, we studied 84 healthy middle-aged men and women who were placed on metabolic diets, for 2 wk, that were supplemented with either wheat bran (n = 42) or oat bran (n = 42). Fiber supplementation was 1.6 micrograms dietary fiber/J (6.8 g dietary fiber/1000 kcal) to a maximum of 16.4 g fiber/d. Significantly greater decrease with oat than with wheat were seen in total cholesterol (0.56 +/- 0.08 mmol/L and 0.29 +/- 0.08 mmol/L, P = 0.022) and low-density-lipoprotein cholesterol (0.39 +/- 0.07 mmol/L and 0.15 +/- 0.07 mmol/L, P = 0.024). No significant differences were seen in high-density lipoprotein, apolipoproteins A-1 and B, or triglyceride. We conclude that oat bran has an advantage over wheat bran in lowering serum lipids when tested in metabolic diets on large numbers of individuals with an initial mean serum cholesterol concentration above the desirable range, at 5.61 +/- 0.16 mmol/L.

Adult↗