Quantitative sonographic feature analysis of clinical infant hypoxia: a pilot study.

PURPOSE: To determine whether textural features derived from sonographic pixel intensities differ significantly between healthy infants and infants who have had acute clinical hypoxic episodes. METHODS: Neurosonographic and calibration phantom-processed image data were evaluated prospectively from 9 infants (age range, 1 to 163 days) with at least 1 episode of hypoxia and compared with image data from a control population of 16 healthy infants (age range, 1 to 191 days). Custom software was used to make 45 textural feature measurements on 40 x 40-pixel regions of interest within brain parenchyma in the distribution of each major cerebral artery, the thalami, and the cerebellum and in a tissue-mimicking calibration phantom. Means comparison testing was followed by logistic regression to assess statistical variation between the patients and the control group. RESULTS: Nine of 45 textural features showed statistically significant differences between mean values comparing the two groups. Mean gray level was the most sensitive predictor of differences between the two populations (mean gray level for healthy subjects was 46.8; mean gray level for patients was 56.3). An average of mean gray values in areas supplied by the posterior cerebral arteries and the cerebellum was even more sensitive for differentiating healthy subjects from patients. CONCLUSIONS: Quantitative sonographic textural feature analysis showed differences between the brains of healthy infants and those of infants with clinical hypoxia.

Induction of diabetes mellitus in Syrian golden hamsters using stored equilibrium solutions of streptozotocin.

Streptozotocin (STZ), a compound composed of a mixture of alpha and beta anomers, is used experimentally for the chemical induction of diabetes mellitus in numerous animal species. It is routinely recommended that STZ be administered rapidly following dissolution because of its alleged instability in solution. In the present study, we examined the effect of varying the length of time from dissolution to administration on the ability of STZ to induce diabetes mellitus in male Syrian golden hamsters and examined STZ stability and state of equilibrium by high-pressure liquid chromatography. Effective diabetes induction was determined by monitoring plasma glucose concentrations 2 and 9 days after STZ treatment. Diabetes was successfully induced with solutions of STZ (50 mg/kg body weight given intraperitoneally on three consecutive days) used either immediately (24 degrees C), 2 hours (24 degrees C), or 5 to 7 days (6 degrees C) after dissolution in 0.1 M acetate buffer at pH 4.4 (storage temperature indicated in parentheses). Mean plasma glucose concentration was significantly higher in all STZ treatment groups at both time points when compared with acetate buffer-treated controls. There was no significant difference in plasma glucose concentration between STZ treatment groups. High-pressure liquid chromatography analysis demonstrated that the alpha- to beta-anomeric ratio of STZ had reached equilibrium in 84 minutes at 24 degrees C and by 26 hours at 6 degrees C following dissolution. Recovery of STZ was greater in solutions stored at 6 degrees C than at room temperature (24 degrees C).(ABSTRACT TRUNCATED AT 250 WORDS)

Effect of streptozotocin diabetes on development of nitrosamine-induced pancreatic carcinoma when diabetes induction occurs after nitrosamine exposure.

Diabetes mellitus has been suggested as a possible risk factor for the development of pancreatic cancer in humans. Previous studies in our laboratory have shown, however, that streptozotocin (STZ) diabetes inhibits the development of cancer of the exocrine pancreas in hamsters when STZ is administered prior to treatment with the pancreatic carcinogen N-nitrosobis(2-oxopropyl)amine (BOP). It has been reported by others that the concurrent administration of BOP and STZ enhances pancreatic carcinogenesis in hamsters. The purpose of the present study was to determine the effect of STZ diabetes on the development of BOP-induced pancreatic carcinoma when STZ is given following exposure to BOP. Groups of Syrian golden hamsters were treated with either BOP only (single s.c. injection, 40 mg/kg body wt at week 0), BOP (single s.c. injection, 40 mg/kg body wt at week 0) plus STZ (50 mg/kg body wt x3 daily i.p. doses at weeks 10, 20 or 30), STZ only (50 mg/kg body wt x3 daily i.p. doses at weeks 10, 20 or 30), or neither BOP nor STZ. The experiment was terminated at 40 weeks after BOP treatment. No significant difference was seen in the incidence of pancreatic cancer between those animals receiving BOP only at week 0 and those receiving BOP at week 0 plus STZ at weeks 10, 20 or 30 of the study. The results would appear to indicate that STZ diabetes, established after BOP tumor initiation, plays no apparent role in the modulation of pancreatic carcinogenesis.

Further studies of enhanced growth of pancreatic carcinoma in diabetes.

Clinical studies suggest that pancreatic cancer occurs more often in persons with diabetes mellitus [1-7]. We have previously shown that the hamster pancreatic carcinoma cell line H2T grows more rapidly when implanted in streptozotocin (STZ)-diabetic hamsters [8]. To determine if enhanced growth of pancreatic carcinoma cells in diabetic hamsters is due to polyphagia associated with diabetes, H2T cells were implanted into the cheek pouch of three groups of animals: normal hamsters (group I), STZ-diabetic hamsters (group II), and STZ-diabetics pairfed to normals (group III). Tumor weights 30 days after implantation were 172 g in group I, 368 g in group II, and 369 g in group III (P less than 0.007). There was no significant difference between the two diabetic groups. Thus, STZ diabetes appears to promote the growth of pancreatic carcinoma cells by a mechanism other than increased nutrient intake by diabetic tumor hosts.

Neuropeptide Y and peptide YY stimulate the growth of exocrine pancreatic carcinoma cells.

Neuropeptides exert inhibitory effects on pancreatic secretion, but their role in the regulation of growth is unknown. This study was executed to evaluate the effects of PYY and NPY on cell growth and 3H-thymidine incorporation in human (MiaPaCa-2, Capan-2) and hamster (H2T) exocrine pancreatic carcinoma cells in vitro. A significant increase in the number of cells after 96 h of treatment with NPY was observed at 0.01 microM in H2T, 0.1 microM in MiaPCa-2 and at 1 microM in Capan-2 cells. PYY was less potent and did not increase significantly cell growth in MiaPaCa-2, but did at 0.1 microM in Capan-2 and at 1 microM concentration in H2T. Stimulation for 48h with NPY increased 3H-thymidine incorporation significantly at 0.01 microM in all cell lines. With PYY, stimulation of 3H-thymidine incorporation occurred in H2T cells at 0.01 microM. 3H-thymidine incorporation after PYY treatment was significantly increased at 0.1 microM in MiaPaCa-2 and at 1 microM in Capan-2 cells. Receptor studies showed low but definite specific binding of both NPY and PYY in all cell lines. The results suggest that NPY and PYY may have a role in the regulation of growth of exocrine pancreatic carcinoma cells.

Importance of diabetes in inhibition of pancreatic cancer by streptozotocin.

Previous studies in our laboratory have demonstrated that the beta-cell toxin streptozotocin (STZ) inhibits the development of exocrine pancreatic cancer in the hamster when STZ is administered prior to treatment with the pancreatic carcinogen N-nitrosobis(2-oxopropyl)amine (BOP). Because the administration of STZ leads to diabetes, we wished to determine whether the presence of diabetes was important in the inhibitory effect of STZ on pancreatic carcinogenesis or whether STZ acted through a mechanism unrelated to diabetes, perhaps by a direct toxic effect on tumor precursor cells. Whole pancreas transplantation was used to create a two-pancreas hamster model to test this hypothesis. The study demonstrated that (1) STZ inhibits the induction of pancreatic cancer in the hamster when given prior to BOP and (2) the inhibitory effect of STZ was demonstrable only when diabetes was present. The inhibitory effect of STZ appears to be systemic, related to diabetes, and not a direct effect on the pancreas.

Diabetes enhances growth of pancreatic carcinoma cells.

Clinical studies suggest that carcinoma of the pancreas may be more common in patients with chronic diabetes mellitus. To examine the effect of diabetes on growth of pancreatic carcinoma, 5 X 10(5) cultured hamster H2T pancreatic carcinoma cells were implanted into the cheek pouches of streptozocin-diabetic and nondiabetic Syrian hamsters. Tumor size and weight and total tumor DNA content 22 days after implantation were significantly greater in animals with diabetes. Thus streptozocin diabetes appears to promote the growth of pancreatic carcinoma cells in the hamster.

Influence of diabetes on susceptibility to experimental pancreatic cancer.

Clinical studies suggest that diabetes mellitus may predispose to the development of pancreatic cancer. The current study investigated the effect of experimental diabetes on the susceptibility of the Syrian hamster to the induction of exocrine pancreatic carcinoma by the carcinogen BOP. Diabetes was induced with the B-cell toxin streptozotocin. Three groups of animals were studied: nondiabetic control animals and animals with streptozotocin-induced diabetes, and a third group of animals in which the diabetogenic effect of streptozotocin was blocked with nicotinamide. Streptozotocin-induced diabetes significantly inhibited the induction of pancreatic carcinoma by BOP, decreasing the incidence of carcinoma to 24 percent compared with an incidence of 75 percent in nondiabetic control animals (p less than 0.002). In diabetic animals, the degree of inhibition of carcinogenesis paralleled the severity of the diabetes. Blocking the diabetogenic effect of streptozotocin with nicotinamide restored the incidence of induced invasive pancreatic carcinoma to that occurring in nondiabetic control animals. In the hamster model, diabetes appears to have a strong influence on susceptibility to the development of pancreatic carcinoma.