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Biomedical subjects

S Halter

Publications and source records attributed to S Halter.

At least 19 recordsLinked to original sources

Cyclooxygenase-2 expression in Barrett's esophagus.

Barrett's epithelium is a recognized premalignant condition for esophageal adenocarcinoma. Nonsteroidal antiinflammatory drugs (NSAIDs) decrease the relative risk of colon cancer in humans and the esophageal tumor load in carcinogen-treated mice. Previous studies provided conflicting results for COX-2 activity in Barrett's mucosa. Pinch mucosal biopsies were collected from Barrett's and adjacent normal esophageal mucosa from 17 patients with Barrett's esophagus. Low-grade dysplasia was found in seven patients. COX-2 protein was undetectable in normal esophageal mucosa. COX-1 protein expression did not vary between normal and Barrett's epithelium. Increased COX-2 protein was detected in Barrett's epithelium in seven patients (41%) but did not differ with or without dysplasia (43% vs 40%). In conclusion, COX-2 protein is increased in 41% of patients with Barrett's epithelium compared to normal esophageal mucosa but did not differ with or without dysplasia. COX-2 induction may be an early event in the development of Barrett's esophagus.

Aged↗

Provider attitudes and use of alternative medicine in a midwestern medical practice in 2001.

OBJECTIVE: To determine the current level of use, referral and desire for service of different complementary and alternative (CAM) therapies among Gundersen Lutheran Medical Center providers. METHODS: A survey was conducted in January of 2001 of all medical and associate staff. RESULTS: The response rate was 79%; 55% reported using 1 or more of 18 therapies for themselves. Over 25% of providers used nutritional supplements, herbal medicines, or hydrotherapy with a patient. Over half of providers had referred a patient for biofeedback or chiropractic care. Over half of providers would like to offer acupuncture, biofeedback, chiropractic care, hydrotherapy, nutritional supplements, or massage to patients in the future. Associate staff, female staff, primary care providers, and those who had personally used CAM therapies were more likely to have used, referred, or wish to offer more therapies in the future. There was little support for aromatherapy, magnetic field therapy, naturopathic medicine, or ethnic healing methods. CONCLUSIONS: Use of and desire for complementary therapies at Gundersen Lutheran was higher than expected by the Integrative Medicine Oversight Committee. Health care organizations should consider having a process in place to manage the increasing demands for complementary and alternative therapies.

Attitude of Health Personnel↗

Methylene blue staining and endoscopic ultrasound evaluation of Barrett's esophagus with low-grade dysplasia.

This study was performed to determine if either methylene blue staining or endoscopic ultrasound helped direct biopsies in patients with a history of Barrett's esophagus with low-grade dysplasia. Patients underwent radial endoscopic ultrasound scanning to measure esophageal wall thickness, followed by endoscopy with methylene blue staining and biopsies. Mean esophageal wall thickness for squamous mucosa (2.3 +/- 0.2 mm), nondysplastic Barrett's (2.6 +/- 0.2 mm), and Barrett's with dysplasia (2.9 +/- 0.3 mm) were similar. With staining, Barrett's mucosa stained blue more often than gastric epithelium (68% vs 15%, respectively; P < 0.001). The sensitivity and specificity for strong staining detecting Barrett's were 68% and 85%, respectively. Barrett's with low-grade dysplasia stained blue less frequently (52%) than nondysplastic Barrett's (74%; P < 0.05), but the positive predictive value for poor staining indicating dysplasia was 41%. Endoscopic ultrasound was not helpful in directing biopsies in these patients. The utility of methylene blue for detecting dysplasia needs further investigation.

Aged↗

Three-dimensional reconstruction of the antennal lobe in Drosophila melanogaster.

We present the first three-dimensional map of the antennal lobe of Drosophila melanogaster, based on confocal microscopic analysis of glomeruli stained with the neuropil-specific monoclonal antibody nc82. The analysis of confocal stacks allowed us to identify glomeruli according to the criteria shape, size, position, and intensity of antibody labeling. Forty glomeruli were labeled by nc82, eight of which have not been described before. Three glomeruli previously shown exclusively by backfills were not discernible in nc82 stainings. We distinguish three classes of glomeruli: (1) "landmark" glomeruli that are constant in all four criteria mentioned above, (2) less well-demarcated glomeruli that deviate in a single criterion, and (3) poorly defined glomeruli that vary in more than one criterion. All class 2 and 3 glomeruli can be identified by comparison with landmark neighbors. To further aid identification, our model assigns glomeruli to five arrays, each of which is defined by a prominent landmark glomerulus. Six glomeruli consist of distinct, but contiguous structural units, termed "compartments." Glomerular variability observed occasionally between males and females is in the same range as between individuals of the same sex, suggesting the lack of a significant sexual dimorphism in the glomerular pattern. We compare the new model with a previous map and address its potential for mapping activity and expression patterns. An important goal of this work was to create three-dimensional reference models of the antennal lobe, which are accessible on-line.

Animals↗

Dysplastic gastroesophageal junction nodules--a precursor to junctional adenocarcinoma.

Adenocarcinoma of the gastroesophageal junction is a disease rapidly increasing in prevalence. The origin of these tumors is unclear. Barrett's esophagus, gastric cardia lesions, and mucus glands of the distal esophagus have been implicated. This case report presents two cases of patients who had chest pain leading to esophagogastroduodenoscopy. Both had small, benign-appearing nodules at the gastroesophageal junction in the absence of Barrett' s esophagus or gastric lesions. Biopsies revealed intestinal metaplasia with dysplasia in one patient and dysplasia of the mucus glands of the esophagus in the other. The first patient was followed for 8 months with serial biopsies, during which time the lesion became progressively more dysplastic, culminating in invasive cancer. These cases are presented to show that 1) benign-appearing gastroesophageal junction nodules may have malignant behavior, and 2) junctional cancer and high grade dysplasia can occur in the absence of Barrett's esophagus or gastric cardia lesions. Gastroesophageal junctional dysplasia/carcinoma may occur in small foci of intestinal metaplasia or in the mucus glands of the distal esophagus.

Adenocarcinoma↗

Effects of mesenteric ischemia and reperfusion on small bowel electrical activity.

UNLABELLED: Previous studies involving basic electrical rhythm (BER) have not been carried out far enough to fully characterize the relationship between mesenteric ischemia and BER. The phenomenon of reperfusion injury has also not been correlated with BER activity. The goal of this study was to characterize changes in BER during mesenteric ischemia and reperfusion and to correlate them with changes in pathology. METHODS: Serosal electrodes were used to record the electrical activity of rabbit jejunum (n = 20) at baseline, during ischemia (90-210 min), and during reperfusion (120-240 min). BER frequency and amplitude were monitored, and biopsies were taken at the end of ischemia and reperfusion. A pathologist blinded to the specimen identity graded the histology on a scale of 0 (no changes) to 6 (transmural necrosis). Paired t test, the Kruskal-Wallis test of non-parametric ranks, and Fisher's r to z test were used for statistical significance where appropriate. RESULTS: BER frequency and amplitude fell significantly after 15 min of ischemia and became undetectable by 90 min of ischemia in all animals. The likelihood that BER would return during reperfusion was highly correlated with length of ischemia (r = 0.99). Longer periods of reperfusion were associated with increasing pathologic grade. CONCLUSIONS: BER frequency and amplitude are very sensitive to ischemia and their changes occur well before histopathologic changes. The variation in electrical activity of the small bowel during ischemia and reperfusion is a dynamic process that reflects the metabolic state of the smooth muscle. If electrical activity of the bowel is to be used for assessment of viability, continuous recordings more accurately reflect the metabolic state of the smooth muscle.

Animals↗

Superconducting quantum interference device magnetometer for diagnosis of ischemia caused by mesenteric venous thrombosis.

Although mesenteric venous thrombosis carries a better prognosis than arterial thrombosis, mortality and morbidity are still high. Previous studies have shown that the basic electrical rhythm (BER) of the bowel decreases early after induction of arterial ischemia. Furthermore, our studies have shown that these changes occur prior to pathologic changes and that they can be recorded noninvasively using a superconducting quantum interference device (SQUID). SQUIDs measure magnetic fields that are created by the electrical activity of the gastrointestinal smooth muscle and have been used to measure the BER of the small intestine in human volunteers. This study was conducted to determine if a SQUID could be used for early noninvasive detection of mesenteric venous ischemia in an animal model. Simultaneous recordings from serosal electrodes and a SQUID outside the abdomen were taken from anesthetized New Zealand rabbits. Recordings were made for 15 minutes before and 90 minutes after injection of thrombin into the superior mesenteric vein. The basic electrical rhythm of the small bowel dropped from 16.42 +/- 0.69 to 8.80 +/- 0.74 cycles per minute at 30 minutes and to 6.82 +/- 0.722 after 90 minutes (p < 0.0001, paired t-test). The correlation coefficient between the SQUID and electrical recordings was 0.954 (p < 0.0001). These data suggest that the ischemia caused by mesenteric venous thrombosis results in changes in the bioelectrical activity, which can be noninvasively detected using a SQUID.

Animals↗

Effect of sublethal liver injury on doxorubicin metabolism.

Centrilobular hepatocyte contribution to doxorubicin (DOX) metabolism and myelotoxicity was probed with bromobenzene (BRB), a known centrilobular hepatotoxin. New Zealand White rabbits were given DOX, 3 mg/kg i.v. After 4 weeks, the rabbits were pretreated i. p. with 2.6 ml/kg 40% solution of BRB in corn oil followed 72 h later with a 3-mg/kg dose of DOX. Pharmacokinetics of DOX after BRB pretreatment was mildly changed from control. Significantly increased plasma concentrations of doxorubicinol and its aglycone product, 7-deoxydoxorubicinol aglycone, were detected. Treatment with BRB alone was not lethal; however, in three of seven rabbits, the combination of DOX and BRB was. The mortality appeared to be related to myelosuppression. We conclude that toxin-induced hepato-cellular necrosis causes increased DOX-induced myelotoxicity. Following BRB pretreatment, the relatively small pharmacokinetic changes of parent compound concentrations as compared with greater changes in plasma pharmacokinetics of its alcohol metabolites suggest systemic changes in drug metabolism and distribution in the setting of hepatic disease may be the cause of increased toxicity.

Animals↗

A model of cytochrome P-450-centered hepatic dysfunction in drug metabolism induced by cobalt-protoporphyrin administration.

Cobalt-protoporphyrin treatment disrupts cytochrome P-450-centered drug metabolism and is known to decrease significantly the cytochrome P-450 content of the liver. This study assesses further the correlations between biochemical and functional changes induced by Co-protoporphyrin. Specifically, it confirmed the fall in cytochrome P-450 levels in liver and demonstrated that both NADPH-cytochrome P-450 reductase and NADH-cytochrome b5 reductase activities decreased in a dose-dependent manner, albeit to a lesser degree, upon Co-protoporphyrin administration. Furthermore, plasma clearance of the marker drug aminopyrine fell off abruptly with a minimal decrease in cytochrome P-450 content, and then monotonically with its further depletion. Both aminopyrine and caffeine demethylation, as measured by the amount of radiolabeled CO2 exhaled, also decreased with diminishing cytochrome P-450 content. With aminopyrine the decrease was abrupt but with caffeine biphasic, consistent with preferential isozyme depletion. The drop in oxidative drug metabolism measured by these two in vivo techniques occurred in the absence of organellar damage to hepatocytes, as observed by electron microscopy. In vitro studies of aminopyrine metabolism in microsomes prepared from rats with and without Co-protoporphyrin injection proved to be consistent with the in vivo studies. Moreover aminopyrine Vmax decreased and Km increased with decreasing cytochrome P-450 content, suggesting preferential isozyme depletion. Furthermore, the changes in aminopyrine intrinsic clearance predicted by the in vitro Vmax and Km values agreed with those measured by in vivo plasma clearance. Taken together, these data suggest that Co-protoporphyrin treatment can be used to produce a model of altered cytochrome P-450-centered drug metabolism, as measured consistently by several techniques. However, this model appears to be more complex than one involving nonspecific depletion of cytochrome P-450 alone, and may be influenced also by concomitant changes in the electron transport chain or other aspects of hepatic metabolism.

Aminopyrine↗

The influence of ranitidine on the pharmacokinetics and toxicity of doxorubicin in rabbits.

The influence of ranitidine on the pharmacokinetics and toxicity of doxorubicin was studied in six female New Zealand white rabbits. Plasma pharmacokinetic data were first obtained from rabbits given 3 mg/kg doxorubicin. After 1 month, the same rabbits were treated with ranitidine, 2.5 mg/kg or 25 mg/kg, before and during doxorubicin administration. The plasma doxorubicin assays to determine pharmacokinetic parameters were repeated. Drug toxicity was evaluated using complete blood counts, and hepatic function was measured using a 14C-aminopyrine breath test. High-dose ranitidine increased the total exposure to doxorubicin (area under the curve of doxorubicin alone = 1.44 +/- 0.88 microM.h/ml vs 4.49 +/- 2.35 microM.hr/ml for doxorubicin given with high-dose ranitidine; P = 0.06). Low-dose ranitidine did not alter doxorubicin pharmacokinetics. Exposure to doxorubicinol was altered by either high-dose or low-dose ranitidine. 14C-Aminopyrine half-life was altered by a ranitidine dose of 25 mg/kg (aminopyrine half-life after placebo control = 97 +/- 6 min as against aminopyrine half-life after ranitidine = 121 +/- 7 min; mean +/- SEM; P less than 0.02). Low-dose ranitidine did not exacerbate doxorubicin-induced myelosuppression. High-dose ranitidine enhanced doxorubicin-induced erythroid suppression while sparing the myeloid series. At cytochrome P-450-inhibitory doses, ranitidine's effects upon doxorubicin plasma pharmacokinetics are similar to those previously seen with cimetidine. These changes did not appear to alter drug detoxification and are not related to microsomal inhibition of doxorubicin detoxification. Low doses of ranitidine do not alter doxorubicin plasma pharmacokinetics or toxicity in rabbits.

Aminopyrine↗

Systemic mastocytosis and mastocytosis-like syndrome: radiologic features of gastrointestinal manifestations.

Mastocytosis is a disorder of unknown etiology characterized by an abnormal proliferation of tissue mast cells, and/or by degranulation of abnormally behaving mast cells that show no proliferation, but release myriad active metabolites. This results in a wide spectrum of signs and symptoms that fluctuate considerably. The presently available diagnostic tests vary in their specificity and sensitivity. We have evaluated the role of radiologic studies in 78 confirmed cases of systemic mastocytosis and/or mastocytosis-like syndrome, including barium meal and small bowel follow-through (UGI-SBFT).

Adolescent↗

Effect of allyl alcohol-induced sublethal hepatic damage upon doxorubicin metabolism and toxicity in the rabbit.

A model of hepatic dysfunction in vivo has been developed in rabbits to determine the effects of sublethal hepatocellular necrosis upon doxorubicin pharmacology. Eight New Zealand white rabbits were given 3 mg/kg doxorubicin i.v. Plasma doxorubicin and metabolite pharmacokinetics were determined and toxicity assessed by nadir complete blood counts. Hepatic function was assessed by the pulmonary excretion rate of 14CO2 from [14C]aminopyrine. Hepatocellular necrosis was produced by i.v. injection of 1.35 mg/kg of a 2% allyl alcohol solution. Doxorubicin administration and pharmacokinetics were repeated. Doxorubicin enhances the hepatotoxicity of allyl alcohol. Hepatocellular necrosis does not alter the plasma pharmacokinetics of doxorubicin but does increase the plasma exposure of doxorubicinol. Doxorubicin-induced myelosuppression is enhanced by allyl alcohol pretreatment. These data suggest that in circumstances of reduced hepatocellular volume or acute hepatocellular necrosis, a key plasma marker of doxorubicin-induced acute toxicity may be doxorubicinol.

1-Propanol↗

Large hypopharyngeal polyp producing intermittent dysphagia and acute airway obstruction.

A 65-yr-old man who developed sudden respiratory arrest was found to have a long, smooth, esophageal filling defect on esophagogram. Endoscopy eventually proved this to be a large esophageal polypoid lesion that had arisen in the hypopharynx and extended to the midesophagus. He was successfully treated with a lateral pharyngotomy and excision of the hypopharyngeal polyp.

Aged↗

Intramucosal gastric carcinoma in a patient with familial polyposis coli.

Upper gastrointestinal polyps commonly occur in patients with familial polyposis coli; but the occurrence of gastric carcinoma is very rare in this disorder. We report a case of intramucosal gastric carcinoma in a patient with familial polyposis coli and multiple gastrointestinal adenomatous polyps.

Adenocarcinoma↗

De novo carcinoma of the rectum: a case report.

There is strong evidence in the literature to suggest that most of the colorectal carcinomas arise from adenomatous polyps. Yet, rare carcinomas may arise de novo and we are reporting such a case of intramucosal rectal carcinoma occurring in a 47-year-old healthy man.

Adenocarcinoma↗