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M J Zinner

Publications and source records attributed to M J Zinner.

At least 37 records · Page 2Linked to original sources
PubMed1996

Perioperative blood transfusions and decreased long-term survival in esophageal cancer.

We evaluated retrospectively the effect of perioperative blood transfusions on survival in esophageal cancer. The records of all patients who underwent esophageal resection (n = 316) at UCLA Medical Center from 1970 to 1993 were reviewed. Statistical analysis included univariate (log-rank chi 2) and multivariate (Cox proportional hazards) analyses with other known risk factors. High-volume blood transfusions (> 8 units) but not low-volume blood transfusions (1 to 8 units) were associated with a significant decrease in long-term survival (median survival: no transfusion, 22 months; low-volume blood transfusion, 14.5 months, versus high-volume blood transfusions, 6.5 months; p < 0.01). Multivariate analysis revealed that the shorter survival with high-volume blood transfusions was a result of an increased number of postoperative complications. High-volume blood transfusions were not associated with increases in tumor recurrence or infectious complications. The association between shorter survival and high-volume blood transfusions in esophageal cancer may, therefore, be because of the circumstances necessitating transfusion rather than any immunosuppressive effects of the transfused blood. These findings suggest that the transfusion of blood does not by itself decrease the chance of cure after esophageal resection.

Adenocarcinoma↗
PubMed1996

Nitric oxide regulates endothelium-dependent vasodilator responses in rabbit hindquarters vascular bed in vivo.

The objective of this study was to determine whether nitric oxide (NO) could function as a negative feedback modulator of endothelium-dependent vasodilation in vivo. To this end, the influence of exogenous NO on vasodilator responses in the rabbit hindquarters vascular bed was determined. Previous in vitro studies have demonstrated that NO inhibits both neuronal NO synthase from rat cerebellum as well as NO synthase derived from bovine aortic endothelial cells. The present study was conducted in the rabbit hindquarters vascular bed under conditions of constant blood flow so that changes in pressure directly reflected changes in vascular resistance. Under these in vivo conditions, the NO donor agent S-nitroso-N-acetylpenicillamine (SNAP) reversibly attenuated responses to the endothelium-dependent vasodilators, acetylcholine and bradykinin. In contrast, SNAP did not influence the endothelium-independent vasodilator response to SNAP itself or to 8-bromoguanosine 3',5'-cyclic monophosphate. These observations indicate clearly that NO interferes with endothelium-dependent vasodilator action and support the view that endogenous NO may actually play a physiological role in regulating vascular tone.

Acetylcholine↗
PubMed1996

Neuronal pathways involved in abdominal surgery-induced gastric ileus in rats.

The 20-min rate of gastric emptying of a noncaloric solution and c-fos expression detected by immunohistochemistry in the brain were monitored 3 h after abdominal surgery performed under 10-min enflurane anesthesia in rats. Abdominal surgery (laparotomy and 1-min manipulation of the cecum) decreased gastric emptying from 60.8 +/- 3.4 to 25.9 +/- 3.4%. Capsaicin applied to the celiac/superior mesenteric ganglia 2 wk before the experiment reduced the delay in gastric emptying induced by abdominal surgery (46.3 +/- 3.4%), whereas perivagal capsaicin application had no effect (23.6 +/- 7.9%). The corticotropin-releasing factor (CRF) antagonist [D-Phe12, Nle21,38,C alpha MeLeu37]CRF-(12--41) injected intracisternally (10-20 micrograms) prevented postoperative gastroparesis induced by surgery, while having no effect on basal gastric emptying. Abdominal surgery increased the number of Fos-positive cells in brain nuclei regulating autonomic outflow: the nucleus of the solitary tract, locus ceruleus, paraventricular nucleus, and supraoptic nucleus of the hypothalamus. These data indicate that capsaicin-sensitive splanchnic afferent fibers and activation of CRF receptors in the brain are part of the neuronal circuitry mediating gastric stasis 3 h after abdominal surgery.

Abdomen↗
PubMed1996

Peptide YY: a potential proabsorptive hormone for the treatment of malabsorptive disorders.

Peptide YY (PYY) is a 36 amino acid peptide that is released from the endocrine cells of the distal ileum, colon, and rectum following a meal. PYY is strongly proabsorptive in the small intestine. We studied the effects of intravenous PYY on colonic water and electrolyte transport in awake dogs. Dogs had 20 cm neurovascularly intact colon Thiry-Vella fistulas (TVS) surgically constructed. Colonic transport was studied in three experimental groups. Group 1 animals received a standard mixed meal. Group 2 animals were unfed and received intravenous PYY and 100 pmol/kg/hr for two hours. This dose of PYY has previously been shown to simulate the plasma levels of PYY normally seen after a meal. Group 3 received intravenous PYY at the same dose in addition to a mixed meal. Our study shows an increase in colonic water, Na+, and Cl- absorption after a meal (P < 0.05). Infusion of PYY at a 100 pmol/kg/hr was significantly proabsorptive beginning at 60 minutes (P < 0.01). Infusion of PYY in addition to a meal further increased absorption (P < 0.05). PYY is a potent proabsorptive agent in the colon of the conscious dog. PYY, or its analogs, may be useful clinical agents in intestinal malabsorptive disorders or after bowel resection.

Animals↗
PubMed1995

Pancreatic peptide YY mRNA levels increase during adaptation after small intestinal resection.

Peptide YY (PYY) is a 36-amino-acid peptide known to inhibit pancreatic and gastrointestinal secretion. Immediately following small bowel resection, intestinal PYY mRNA and plasma PYY levels rise. The purpose of this study was to determine whether PYY expression changes in the pancreas during the adaptive period after extensive small bowel resection. Female Sprague-Dawley rats (250 g) underwent 70% small intestinal resection or transection alone as control. Animals were sacrificed at 6 hr, 24 hr, 1 week, or 2 weeks following operation (N = 5/time group). Pancreatic tissue was harvested and RNA was isolated by the guanididium-thiocyanate method. PYY mRNA was analyzed by reverse transcriptase PCR, standardized to glyceraldehyde-3-phosphate dehydrogenase, and semiquantitated by Southern blotting and 32P cpm. Ribonuclease protection assay was used to confirm PCR results. PYY mRNA expression was increased 9 1/2-fold beginning 6 hr after resection compared to transection (P < 0.05). PYY mRNA levels remain elevated, 2 1/4-fold greater than control after 2 weeks (P < 0.05) as analyzed by reverse transcriptase PCR and ribonuclease protection assay. Quantitation by ribonuclease protection assay reveals a gradual elevation of PYY mRNA levels in transected animals compared to a nonoperated rat starting at 1 and 2 weeks. Pancreatic PYY mRNA levels increase rapidly after extensive intestinal resection and remain elevated 2 weeks postoperatively. These results confirm for the first time that the increase in PYY seen after extensive intestinal resection also occurs in extraintestinal sites. In the pancreas, elevated PYY levels may inhibit exocrine secretion, reducing luminal volume, and thereby facilitating intestinal adaptation.

Adaptation, Physiological↗
PubMed1995

Amino acids mediate postprandial jejunal proabsorption.

Ingestion of a meal stimulates small intestinal ion and water transport. Current evidence suggests that this response, termed proabsorption, is primarily mediated by the apical Na+/glucose cotransporter. Like glucose, the majority of amino acid absorption occurs by Na(+)-dependent, secondary active transport. The purpose of this study was to determine the role of amino acid transport in meal-induced jejunal ion and water absorption in vivo. Exteriorized, neurovascularly intact jejunal loops measuring 25 cm were created in six female mongrel dogs, and the dogs were allowed to recover for 2 weeks. After an overnight fast, the loops were perfused with a standard buffer containing 10 mM aspartate, leucine, glycine, or lysine. Net water and electrolyte absorption before and after a mixed meal was calculated using [14C]polyethylene glycol as a volume marker. Aspartic acid, leucine, glycine, and lysine are each transported by a separate transporter system. Except for lysine, each amino acid significantly (P < 0.05) potentiated sodium and water absorption after a meal. In addition, this effect was at least as great as that seen with 10 mM glucose. These results demonstrate that amino acid transporter, like the Na+/glucose cotransporter, mediates meal-induced jejunal sodium and water absorption and may be as important in the proabsorptive response.

Amino Acids↗
PubMed1995

A novel synthetic analog of peptide YY, BIM-43004, given intraluminally, is proabsorptive.

Peptide YY (PYY), a proabsorptive hormone, is released into the circulation and lumen of the small intestine after a meal. We have recently found that intraluminal PYY is proabsorptive in the ileum. The purpose of this study was to examine the effects of intraluminal administration of a new substituted PYY (22-36) analog on intestinal absorption of electrolytes and water. Twelve conditioned 20-kg dogs had 25-cm jejunal, 25-cm ileal, or 20-cm colonic Thiry-Vella fistulas (TVF) surgically constructed under general anesthesia (jejunal and ileal TVF, N = 6, and colonic TVF, N = 6). After a 2-week recovery period, the animals received the intraluminal PYY analog, BIM-43004, in the ileum (200 pmole/kg) or colon (300 pmole/kg) for 60 min after a 90-min steady-state basal period was confirmed. The TVF were perfused with an isotonic buffer solution containing [14C]polyethylene glycol as a volume marker. Ion and water transport were measured every 15 min. Net water absorptions were significant in the ileum and colon but not in the jejunum upon intraluminal administration of the PYY analog, BIM-43004. Colonic water absorptions were increased more than twofold above basal absorption rates and ileal absorptions were increased more than 1.5-fold upon addition of intraluminal BIM-43004. Sodium and chloride ion absorption in the colon and ileum paralleled water fluxes. We are describing for the first time a synthetic peptide analog of PYY that produces significant water and electrolyte absorption in the ileum and colon when administered luminally. This synthetic analog may have therapeutic potential in patients with malabsorptive disorders.

Animals↗
PubMed1995

Na+/H+ exchange mediates postprandial ileal water and electrolyte transport.

Feeding stimulates fluid and electrolyte absorption in the small intestine. Previous studies have suggested that Na+/glucose cotransport is important in initiating this response in the jejunum. The purpose of this study was to determine whether Na+/H+ exchange plays a role in meal-induced absorption. Exteriorized, neurovascularly intact jejunal and ileal loops (25 cm) were constructed in dogs. Following a two-week period of postoperative recovery, the loops of awake dogs were perfused with standard buffer alone or with increasing concentrations of amiloride, a Na+/H+ exchange inhibitor. Water, sodium, and chloride fluxes were calculated following a meal using [14C]PEG as a volume marker. The meal significantly increased absorption in both the jejunum (P < 0.001) and ileum (P < 0.01) in those animals perfused with buffer alone. More significantly, amiloride suppressed the increased absorption seen following a meal in the ileum (P < 0.001) but not the jejunum. The response in the ileum was dose dependent. These findings suggest that a major mediator of postprandial sodium and water absorption in the ileum is the Na+/H+ exchanger.

Amiloride↗
PubMed1995

Changes in the surgical management of esophageal cancer from 1970 to 1993.

PURPOSE: To evaluate the changes since 1970 in the management and outcome of esophageal resection for cancer. METHODS: The records of all 316 patients who underwent esophageal resection for cancer at University of California Los Angeles Medical Center during the years 1970 to 1993 were reviewed. RESULTS: When records from 1984 to 1993 were compared to those from 1970 to 1983, significant decreases were seen in operative mortality (10% to 3%, P < 0.01), morbidity (72% to 60%, P < 0.05), anastomotic leaks (12% to 5%, P < 0.03), and reoperations (20% to 8%, P < 0.003). Time spent in hospital and in intensive care decreased 40%. These improvements in short-term outcome were most evident in patients with disease in later stages. The 5-year survival rate increased (12% to 21%, P < 0.01). A greater percentage of tumors presented in early stages (21% versus 37%). CONCLUSIONS: Short-term outcome of surgical resection for esophageal carcinoma improved between 1970 and 1993, in part because of changes in perioperative and surgical management. Long-term survival improved, probably due to earlier detection of tumors.

Adenocarcinoma↗
PubMed1995

Solid and papillary neoplasms of the pancreas.

Solid and papillary neoplasms of the pancreas are rare, low-grade malignant tumors histologically distinct from usual ductal adenocarcinomas and islet cell tumors and amendable to cure by surgical excision. Because these lesions have been incorrectly diagnosed in the past as adenocarcinomas or cystadenocarcinomas, they may have contributed to reports with confusing survival statistics following resections for malignant neoplasms of the pancreas. In young women with large, relatively asymptomatic tumors of the pancreas, solid and papillary neoplasms should be high on the list of the differential diagnoses.

Adenocarcinoma↗
PubMed1995

Early regional expression and secretion of peptide YY and enteroglucagon after massive resection of small bowel.

BACKGROUND: Previous studies suggest that peptide YY (PYY) and enteroglucagon have an important role in intestinal adaptation after massive small bowel resection. This study was done to define the mechanisms, timing, and anatomic distribution of the PYY and enteroglucagon response. STUDY DESIGN: Lewis rats underwent resection of 70 percent of the small bowel (leaving equal segments of jejunum and ileum), transection, or laparotomy alone. Jejunum, ileum, and colon were compared in resected, transected, and control bowel six hours, 24 hours, one week, and two weeks postoperatively. RESULTS: Analysis of DNA, RNA, and protein per cm of bowel demonstrated hyperplastic changes. Radioimmunoassay revealed plasma PYY and enteroglucagon to be significantly elevated 24 hours after resection and they remained so through week two. In contrast, tissue PYY and enteroglucagon content decreased significantly in all tissues (p < 0.05) after resection. Reverse transcriptase polymerase chain reaction and Southern blot analysis demonstrated an immediate and sustained increase in PYY messenger RNA (mRNA) in both the ileum (fourfold) and in the colon (2.5-fold) at six hours (p < 0.05). A gradual increase in PYY mRNA was also demonstrated in the jejunum with significance at two weeks (p < 0.05). Proglucagon mRNA was significantly higher in the jejunum, compared with the ileum and colon, at 24 hours, one week, and two weeks postresection. CONCLUSIONS: Alterations in PYY and enteroglucagon synthesis occur early in the ileum and colon after massive small bowel resection. The residual jejunum, however, is primarily responsible for the adaptive hyperenteroglucagonemia. These findings suggest that although PYY and enteroglucagon are colocalized to the same cell type, there is a gene-specific response for these two peptides after resection.

Adaptation, Physiological↗
PubMed1994

Successful engraftment of autologous and allogeneic islets into the porcine thymus.

Work in rodents has shown that injection of pancreatic islets of Langerhans into the thymus can induce donor-specific unresponsiveness to islets subsequently transplanted to extrathymic sites. The overall objective of our investigation is to test this in a large animal (pig) model. In the current study we examined whether autologous and allogeneic adult or fetal islets survive in the porcine thymus. Collagenase-digested adult and fetal porcine islets were injected into the thymic lobes of 5- to 13-month-old, normal pigs. Pigs receiving allografts were given either a standard triple regimen of oral cyclosporine, azathioprine, and prednisone or intravenous anti-lymphocyte globulin (ALG) for immunosuppression. Two pigs of each group that received an allograft or autograft were given no immunosuppression. Biopsies of the grafts were taken at 4, 6, or 12 weeks for examination. Islet survival was assessed by histology with hematoxylin and eosin and insulin staining and by measurement of tissue insulin content using acid alcohol extraction and radioimmunoassay. The insulin content of control thymus was found to be 0.71 +/- 0.29 microU/mg (n = 5). The insulin content of the islet-grafted thymic tissues ranged from 1.57 to 10.65 microU/mg. Since the amounts of injected islets were not equal and not distributed evenly, and only a part of the graft site was used for determination of tissue insulin, thymic insulin contents higher than 1.4 microU/mg (twice that of the control value) were considered to demonstrate the presence of viable islets. With this criterion, we concluded that islets were found to be viable in seven of nine pigs and two pigs which were treated with ALG were shown to be marginally positive. On histological examination, islets were found in the thymus as well as under the thymic capsule, except for the above two pigs. These results demonstrate that the pig thymus supports fetal and adult islet transplants.

Animals↗
PubMed1994

Adaptation of the Na+/glucose cotransporter following intestinal resection.

Following massive small bowel resection, the remaining intestine adapts to compensate for lost absorptive capacity. Although the Na+/glucose cotransporter plays a critical role in nutrient, fluid, and electrolyte transport in the small intestine, its role in adaptation following resection has not been defined. To examine this, we sought to determine whether there were changes in the expression of the Na+/glucose cotransporter, SGTL1, at the messenger RNA level. Lewis rats underwent either transection or 70% small bowel resection and reanastomosis. The animals were sacrificed at intervals following operation. Jejunum proximal to the anastomosis and ileum and colon distal to the anastomosis were harvested and analyzed for Na+/glucose mRNA by reverse transcriptase-polymerase chain reaction and Southern blot. Blots were semiquantitated by 32P labeling and standardized to beta-actin. Histologic sections and analysis of DNA, RNA, and protein content revealed hyperplastic changes. Following resection, mRNA for the Na+/glucose cotransporter in the jejunum increased significantly (P < 0.05) by 1 week and remained elevated. In the ileum, an almost fivefold increase occurred at 6 hr and persisted throughout the study (P < 0.05). The early response was greater in the ileum, distal to the reanastomosis, than that in the jejunum (P < 0.05). In contrast, there was no change in the small amount of transporter mRNA detected in the colon. These results suggest that, in addition to mucosal hyperplasia, the intestinal response to resection involves upregulation of transporter mRNA by the individual enterocyte. This transcriptional increase in the Na+/glucose cotransporter appears to be an early response by the intestine and may be important in maintaining overall intestinal transport capacity following resection.

Adaptation, Physiological↗
PubMed1994

Neurohumoral mechanism involved in augmentation of canine jejunal absorption following oral rehydration solutions.

Throughout the world diarrheal diseases kill over 5 million children annually. Oral rehydration therapy, initially using glucose-based solutions and more recently cereal-based solutions, prevents complications and death from dehydration. These experiments compared the effect of these two rehydration solutions and a mixed meal on jejunal water and ionic transport. Five dogs had 25-cm proximal jejunal Thiry-Vella fistulae constructed. Following recovery, jejunal absorption studies (N = 40) were performed using an isotonic electrolyte solution containing [14C]PEG to calculate net fluxes of water, sodium, and chloride. Each study consisted of a 1-hr basal period, followed by a 3-hr experimental period. Each animal was randomly studied in each of four study groups: control, mixed meal, glucose-based and cereal-based rehydration solution. In the mixed meal, glucose-based, and cereal-based solution groups there were significant increases (P < 0.0001) in jejunal Thiry-Vella fistula water and ion absorption following the stimuli, in the absence of direct luminal nutrient contact with the Thiry-Vella fistula. There were no differences between the observed responses to the glucose-based or cereal-based rehydration solutions. Glucose-based and cereal-based rehydration solutions were equally effective in stimulating jejunal absorption of water and electrolytes, but less effective than a mixed meal. Both food and oral rehydration solutions appear to increase jejunal absorption partially via a neurohumoral mechanism that is independent of luminal nutrient contact with the Thiry-Vella fistula.

Animals↗
PubMed1994

Meal-stimulated canine jejunal ionic absorption. Influence of mucosal neural blockade.

The oral ingestion of a meal or the delivery of nutrients directly to the stomach or duodenum stimulates water and ion absorption from the proximal jejunal lumen. To further investigate this phenomenon, this study tested two hypotheses: (1) direct jejunal nutrient delivery stimulates jejunal absorption, and (2) the signal for jejunal absorption requires intact enteric neurotransmission and will therefore be altered by mucosal neural blockade with the local anesthetic bupivacaine. Intestinal absorption studies (N = 52) were performed on eight dogs with 25-cm jejunal Thiry-Vella fistulas (TVF) and feeding jejunostomies. Luminal perfusion with [14C]PEG was used to calculate TVF absorption of H2O, Na+, and Cl-. Six groups were randomly studied over 4 hr. Each group incorporated a basal hour, a TVF or jejunostomy treatment hour, and an oral (groups 1 and 3) or a jejunal (groups 4 and 6) meal stimulus. The oral and jejunal meals were isocaloric and of identical composition. Groups 1-3 had saline (as a control) or 0.75% bupivacaine applied to the lumen of the TVF. Groups 5 and 6 had 0.75% bupivacaine application to the feeding jejunostomy. Both the oral and the jejunal meal stimuli resulted in a significant proabsorptive response in the TVF. TVF bupivacaine reduced basal absorption but did not diminish the meal-induced proabsorptive response. Treatment of the jejunostomy with bupivacaine caused no change in basal or postmeal absorption in the TVF.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1994

Peptide YY augments postprandial small intestinal absorption in the conscious dog.

Since feeding increases intestinal fluid and electrolyte losses in short bowel syndrome, an agent increasing postprandial small bowel absorption might have a therapeutic role. Peptide YY (PYY) has recently been shown to increase net small bowel absorption under basal conditions. The aim of this study was to determine whether PYY can also augment postprandial absorption. Exteriorized, neurovascularly intact jejunal and ileal segments (25 cm Thiry-Vella loops) were created in dogs (n = 6) and gastrointestinal continuity was restored. Luminal perfusion with [14C]polyethylene glycol was used to calculate the change in water (H2O) and sodium (Na+) and chlorine (Cl-) ion fluxes after an oral meal. Changes in fluxes were also determined after a 2-hour infusion of a physiological dose of PYY (100 pmol/kg per hour). In a third series of experiments, fluxes were measured after a meal, during PYY infusion. Feeding increased small bowel absorption of fluid and electrolytes independent of the luminal content. This effect persisted for 2 hours after the meal. PYY infusion significantly augmented this proabsorptive response in both jejunum and ileum. These results suggest that PYY-agonists may have a therapeutic role in conditions such as short bowel syndrome where postprandial absorption is reduced.

Analysis of Variance↗
PubMed1994

Gastroduodenal disease in the elderly patient.

Benign and malignant diseases of the stomach and duodenum are common in the elderly. Atypical presentations frequently are seen, making early diagnosis difficult. Aggressive surgical and medical management regimens are usually possible, giving cure rates comparable to those seen in the younger population.

Aged↗