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Biomedical subjects

M J Zinner

Publications and source records attributed to M J Zinner.

At least 55 records · Page 3Linked to original sources

Peptide YY immunoneutralization inhibits meal-induced absorption in vivo.

BACKGROUND: Plasma peptide YY (PYY) levels rise after a meal and have recently been shown to increase small bowel-absorption. The purpose of this study was to determine whether immunoneutralization of PYY would block postprandial absorption in vivo. METHODS: Exteriorized, neurovascularly intact jejunal and ileal segments (25 cm) were created in six mongrel dogs. After a 2-week recovery luminal perfusion with an isotonic buffer, containing [14C]-polyethylene glycol as a volume marker, was used to analyze water and sodium flux after an oral meal. Each meal was accompanied by either intravenous anti-PYY (0.5 mg.kg-1.h-1) or nonspecific immunoglobulin IG (control). PYY antibody binding was determined by radioimmunoassay. RESULTS: Displacement studies showed complete PYY neutralization. In control experiments feeding increased absorption of sodium and water in both segments. PYY immunoneutralization had no effect on jejunal absorption but significantly diminished ileal absorption (p < 0.05). CONCLUSIONS: These results suggest that PYY acts selectively in the ileum to increase postprandial fluid and electrolyte absorption after a meal. Agents directed at PYY-stimulated absorption may prove to be of therapeutic benefit in patients with malabsorptive conditions.

Animals↗

Up-regulation of Na+,K+ adenosine triphosphatase after massive intestinal resection.

BACKGROUND: The mechanisms of intestinal adaptation after resection are not completely defined. The purpose of this study was to examine the changes after resection in the enterocyte basolateral Na+,K+ adenosine triphosphatase (ATPase) known to play a critical role in epithelial transport and homeostasis. METHODS: Lewis rats underwent 70% small bowel resection or transection. At 6 hours, 24 hours, 1 week, and 2 weeks, jejunum and ileum were harvested for analysis of Na+,K+ ATPase activity, kinetic analysis, and alpha 1-ATPase messenger RNA and protein levels. RESULTS: Na+,K+ ATPase activity increased (p < 0.05) in both the jejunum and ileum by 2 weeks after resection. This rise in activity correlated with an increase in the maximal activity of ATPase, from 20.8 to 101.01 mumol inorganic phosphate.mg-1.hr-1. ATPase messenger RNA levels increased sixfold in the jejunum and tenfold in the ileum by 2 weeks after resection (p < 0.05). Protein levels rose at 6 hours and remained elevated in both tissues. CONCLUSIONS: After intestinal resection, enterocyte Na+,K+ ATPase activity rises as a result of an increase in the number of transporters per cell. This occurs through both transcriptional and translational mechanisms. It appears that intestinal adaptation after resection involves not only an increase in absorptive surface area but also functional adaptation by the individual enterocyte.

Adaptation, Physiological↗

Malignant mixed tumor (carcinosarcoma) of the pancreas: a case report supporting organ-induced differentiation of malignancy.

BACKGROUND: We present an unusual case of a malignant mixed tumor (carcinosarcoma) of the head of the pancreas that was surgically resected and whose tissue pathologic condition supported the concept of organ-induced differentiation of malignancy. METHODS: After a pancreaticoduodenectomy, tissue sections from various anatomic regions of the tumor were studied by routine histologic examination and immunocytochemistry. Genomic DNA from various regions of the tumor was extracted and digested with Hpa II, and a 511 bp region of the hypoxanthine phosphoribosyltransferase gene was amplified with the polymerase chain reaction to assess clonality. RESULTS: The pathologic findings revealed areas of both adenocarcinoma and leiomyosarcoma, but these disparate areas were not randomly distributed but rather were polar in nature. The adenocarcinomatous areas localized to the tumor within the head of the pancreas, an area of normal ontogenetic glandular development, whereas the leiomyosarcomatous areas localized to regions of the tumor infiltrating the duodenal wall, an area of normal ontogenetic smooth muscle development. Both the adenocarcinomatous and the leiomyosarcomatous areas showed evidence of monoclonality and clonal identity. CONCLUSIONS: This interesting polar distribution of histologic patterns illustrated by this malignant mixed tumor (carcinosarcoma) supports the hypothesis of organ-induced differentiation of malignancy.

Adenocarcinoma↗

Peptide YY is a physiological regulator of water and electrolyte absorption in the canine small bowel in vivo.

BACKGROUND: Peptide YY (PYY), a hormone released following a meal, is one potential mediator of intestinal absorption. Although PYY inhibits 5'-cyclic adenosine monophosphate (cAMP)-stimulated small intestinal secretion in vitro, its effects on fluid and electrolyte transport in vivo are unknown. METHODS: This study examines the effects of physiological doses of PYY in dogs (n = 6) with jejunal and ileal exteriorized, neurovascularly intact intestinal loops (Thiry-Vella fistulas). RESULTS: Plasma PYY levels increased after a meal from 155 +/- 15 to 324 +/- 26 pmol/L at 30 minutes and remained elevated for 2 hours. PYY infused intravenously in unfed animals at 25, 50, 100, and 200 pmol.kg-1.h-1, produced a dose-dependent increase in plasma PYY levels. At 100 pmol.kg-1.h-1, PYY plasma concentrations were similar to those of fed animals (317 +/- 39 pmol/L). PYY infusion resulted in a dose-dependent increase in water and electrolyte absorption at all doses in both the jejunum and ileum. Although the relative increase in absorption was similar, the magnitude was greater in the ileum. CONCLUSIONS: Physiological concentrations of PYY produced an increase in small bowel absorption of water and electrolytes in vivo. The postprandial release of PYY may mediate the increase in absorption following a meal. Such a proabsorptive agent may have considerable potential for clinical use in malabsorptive states.

Animals↗

Production of endothelium-derived relaxing factor (EDRF) is compromised after ischemia and reperfusion.

Rabbit hind limbs were subjected to 5 hours of ischemia with or without 1 hour of in vivo reperfusion, and the response of femoral artery segments to vasocontrictors and vasodilators was studied in vitro. The ability of endothelium-derived relaxing factor (EDRF)-dependent vasodilators to relax arterial segments was not altered after up to 5 hours of ischemia alone but was significantly decreased after 4 hours of ischemia if followed by 1 hour of in vivo reperfusion. Thus, we concluded that a specific injury occurs to endothelial cells after ischemia-reperfusion, which occurs solely during the reperfusion period.

Acetylcholine↗

Small bowel origin and calorie dependence of a signal for meal-induced jejunal absorption.

The ingestion of a meal stimulates the absorption of water and electrolytes from the small intestine independent of the cephalic or gastric phases of digestion. This study tested two hypotheses: (1) the jejunum is the origin of a postmeal proabsorptive signal and (2) the magnitude of the proabsorptive response is dependent on the caloric content of the meal stimulus. Twenty-five-centimeter proximal canine jejunal Thiry-Vella fistulas and feeding jejunostomies were constructed under general anesthesia. Jejunal absorption studies (n = 50) were performed by luminal perfusion of the Thiry-Vella fistula with 14C-polyethylene glycol (PEG) to calculate fluxes of water and electrolytes. Five groups were studied: (1) CONTROL: no meal, (2) 240 kcal oral meal, (3) 480 kcal oral meal, (4) 240 kcal jejunal meal, and (5) 480 kcal jejunal meal. Independent of the route of delivery (i.e., oral vs. jejunal), each meal stimulus significantly increased jejunal water and electrolyte absorption (p < 0.05). The magnitude of the proabsorptive response increased significantly as the calories delivered increased (p < 0.05). These data support the hypothesis that a proabsorptive signal responsible for meal-induced jejunal absorption originates from, or distal to the jejunum and suggest that intestinal chemoreceptors or osmoreceptors participate in the generation of the proabsorptive signal.

Animals↗

Open cholecystectomy. A contemporary analysis of 42,474 patients.

OBJECTIVE: This study evaluated, in a large, heterogeneous population, the outcome of open cholecystectomy as it is currently practiced. SUMMARY BACKGROUND AND DATA: Although cholecystectomy has been the gold standard of treatment for cholelithiasis for more than 100 years, it has recently been challenged by the introduction of several new modalities including laparoscopic cholecystectomy. Efforts to define the role of these alternative treatments have been hampered by the lack of contemporary data regarding open cholecystectomy. METHODS: A population-based study was performed examining all open cholecystectomies performed by surgeons in an eastern and western state during a recent 12-month period. Data compiled consisted of a computerized analysis of Uniformed Billing (UB-82) discharge analysis information from all non-Veterans Administration (VA), acute care hospitals in California (Office of Statewide Planning and Development [OSHPD]) and in Maryland (Health Services Cost Review Commission [HSCRC]) between January 1, 1989, and December 31, 1989. This data base was supplemented with a 5% random sample of Medicare UB-82 data from patients who were discharged between October 1, 1988, and September 30, 1989. Patients undergoing cholecystectomy were identified based on diagnosis-related groups (DRG-197 and DRG-198), and then classified by Principal Diagnosis and divided into three clinically homogeneous subgroups: acute cholecystitis, chronic cholecystitis, and complicated cholecystitis. RESULTS: A total of 42,474 patients were analyzed, which represents approximately 8% of all patients undergoing cholecystectomy in the United States in any recent 12-month period. The overall mortality rate was 0.17% and the incidence rate of bile duct injuries was approximately 0.2%. The mortality rate was 0.03% in patients younger than 65 years of age and 0.5% in those older than 65 years of age. Mortality rate, length of hospital stay, and charges were all significantly correlated (p < 0.001) with age, admission status (elective, urgent, or emergent), and disease status. CONCLUSIONS: These data indicate that open cholecystectomy currently is a very safe, effective treatment for cholelithiasis and is being performed with near zero mortality. The ultimate role of laparoscopic cholecystectomy needs to be defined in the context of current and contemporary data regarding open cholecystectomy.

Acute Disease↗

Biliary complications of laparoscopic cholecystectomy.

Laparoscopic cholecystectomy has rapidly become the preferred treatment for symptomatic gallstones. Although this procedure has certain advantages over open cholecystectomy, concern has been expressed regarding the potential for bile duct injuries. In an effort to understand the scope of this problem, a retrospective review was performed of all patients referred to UCLA after having sustained biliary injuries during laparoscopic cholecystectomy. Over a 14-month period, 10 patients were referred to UCLA with 12 major bile duct injuries. One patient had a false positive cholangiogram leading to an unnecessary biliary-enteric bypass and subsequent dehiscence, resulting in a biliary fistula. Six patients were referred on an acute basis, whereas four patients underwent attempted biliary reconstruction at outside facilities and were ultimately referred with either a biliary stricture or a fistula. Review of cholangiograms suggested that bile duct anomalies were present in five patients. There did not appear to be a relationship between the use of either electrocautery or laser and bile duct injuries. To date eight patients have been successfully managed via Roux-en-Y hepaticojejunostomies, with a mortality rate of 0%. Although the exact frequency cannot be ascertained from the current study, our data demonstrate that major biliary complications do occur during laparoscopic cholecystectomy. Most of these injuries, however, can be safely and successfully treated with surgical biliary reconstruction. Early diagnosis and treatment with liberal use of intraoperative cholangiography and a low threshold for conversion to open laparotomy appears to be associated with a more favorable outcome.

Adult↗

Management of bile duct strictures. An evolving strategy.

In an effort to determine the role of interventional radiologic and endoscopic techniques in the management of benign biliary strictures, a retrospective analysis was carried out on 194 consecutive patients with bile duct strictures treated at UCLA between 1955 and 1990. Patients were classified as group 1 (1955 through 1979; n = 138) or group 2 (1980 through 1989; n = 56). Follow-up was for a minimum of 24 months and was in excess of 3 years in 179 patients (92%). Although the incidence of recurrent strictures was similar in the two groups (21% and 23%), the reoperation rate was significantly lower (P less than .02) in group 2 (6%) than in group 1 (21%). Percutaneous transhepatic biliary dilatation, used in 20 patients in group 2, was successful in 13 (93%) of 14 patients with anastomotic strictures and three (50%) of six patients with primary strictures (P less than .05). We conclude that surgical reconstruction remains the standard therapy for patients with primary bile duct strictures. Percutaneous transhepatic biliary dilatation has limited usefulness for these patients, but may be more appropriate for those with anastomotic strictures.

Adolescent↗

Meal-stimulated canine jejunal ionic absorption. Effect of direct jejunal meal delivery and premeal intravenous hydration.

The ingestion of a meal stimulates water and ion absorption from the small intestine. The administration of nutrient substances directly to the small bowel can cause dumping symptoms, with intraluminal fluid accumulation and relative systemic hypovolemia. This study compared the effect of oral versus direct jejunal meal delivery on jejunal water and ion absorption, with and without premeal intravenous saline infusion. Jejunal absorption studies (N = 40) were performed on dogs with 25 cm proximal jejunal Thiry-Vella fistulas and feeding jejunostomies. Luminal perfusion with [14C]PEG was used to calculate fluxes of water and electrolytes. Five groups were randomly studied: (1) intravenous 0.9% saline alone, (2) oral meal alone, (3) intravenous 0.9% saline plus oral meal, (4) jejunal meal alone, and (5) intravenous 0.9% saline plus jejunal meal. Hydration status was assessed hourly by measurement of hematocrit. Water and electrolyte absorption was significantly stimulated by both oral and jejunal meal delivery (P less than 0.01). Intravenous saline hydration significantly reduced the hematocrit (P less than 0.05) but did not alter the proabsorptive response to an oral or jejunal meal. In conclusion, a postprandial signal for proximal jejunal water and electrolyte absorption was stimulated equally by orally or jejunally administered nutrients and was not affected by premeal hydration. These data support the hypothesis that the proabsorptive signal that stimulates water and ion absorption is an enteroenteric phenomenon originating from the small intestine, without implicating pathophysiologic events such as hypovolemia or dumping.

Animals↗

Meal-induced jejunal absorption requires intact neural pathways.

A signal for meal-induced absorption originates from the small intestine and is transmitted to a luminally excluded segment of the proximal jejunum (Thiry-Vella [TV] fistula). Using intraluminal topical anesthesia with oxethazaine, this study assessed the role of intestinal neural pathways in basal and postprandial jejunal water and electrolyte absorption. Studies (n = 45) were performed on dogs with 25-cm proximal jejunal TV fistulae and feeding jejunostomies, using luminal perfusion with 14C-polyethylene glycol. The animals were randomized into five study groups: (1) jejunostomy oxethazaine alone, (2) jejunostomy water and jejunal meal, (3) jejunostomy oxethazaine and jejunal meal, (4) TV fistula water and jejunal meal, and (5) TV fistula oxethazaine and jejunal meal. The jejunal meal significantly increased TV fistula absorption, whereas oxethazaine significantly reduced basal absorption when administered via the TV fistula and postprandial absorption when administered via the jejunostomy (p less than 0.05). TV fistula oxethazaine did not diminish the magnitude of postprandial absorption. We conclude that intact intestinal neurotransmission is necessary for maintenance of the normal basal absorptive state of the proximal jejunum and for the generation of a normal meal-stimulated proabsorptive signal from the small intestine. A nonneural mechanism appears to be of predominant importance in transmitting the proabsorptive signal from the intact gastrointestinal tract to the TV fistula.

Anesthetics, Local↗

Influence of meal composition on canine jejunal water and electrolyte absorption.

The absorption of water and electrolytes from the proximal jejunal lumen increases immediately after a meal. This meal-induced jejunal absorption occurs in jejunal segments out of normal gastrointestinal continuity. This study was designed to characterize the jejunal absorptive response to a series of isovolumetric gavage-delivered stimuli. Twenty-five-centimeter canine proximal jejunal Thiry-Vella fistulas were constructed, and jejunal absorption studies (n = 66) were performed by luminal perfusion of the jejunal segments with an isotonic buffer containing 14C-labeled polyethylene glycol. Each study consisted of a 1-hour basal period, followed by a 3-hour experimental period. Nine groups were studied, each receiving one of the following isovolumetric stimuli delivered via the gavage route: water, 0.9% saline, mixed meal, protein, lipid, carbohydrate, and mannitol (150 mmol/L, 300 mmol/L, and 600 mmol/L). The water and 0.9% saline gavage groups showed no significant changes in integrated postprandial water and electrolyte absorption above basal. The isocaloric mixed meal, protein, lipid, carbohydrate, and mannitol groups all had significantly increased integrated postprandial jejunal water and electrolyte absorption above basal (P less than 0.05). These results indicate that a proabsorptive signal for meal-induced jejunal absorption originates from or distal to the stomach. Meal-induced jejunal absorption occurs in response to nutrients of diverse composition and is also responsive to nonnutritive solutes such as mannitol. These findings support a new role for gastric or intestinal chemo- or osmo-receptors in stimulating the neurohumoral mechanisms that mediate meal-induced jejunal absorption.

Analysis of Variance↗

Site-specific variations in basal and meal-stimulated intestinal absorption.

The ingestion of a meal increases water and electrolyte absorption in the proximal jejunum. The purpose of these experiments was to elucidate any site-specific variations in intestinal absorption, comparing jejunum to ileum, in both the basal and the meal-stimulated states. Twenty-five-centimeter proximal jejunal and distal ileal Thirty-Vella fistulae were constructed in four dogs. Simultaneous jejunal and ileal absorption studies were performed using [14C]PEG to calculate net absorption of water and electrolytes. Two groups were studied: in Group 1 no meal was ingested, while in Group 2, the animals ingested a mixed meal. Each study consisted of a 1-hr basal period and a 3-hr experimental period. In the basal state ileal absorption significantly exceeded jejunal absorption (P less than 0.0001). The ingestion of mixed meal significantly increased water and electrolyte absorption in both the jejunum and the ileum, (P less than 0.001), with the magnitude of meal-stimulated ileal absorption significantly exceeding the magnitude of meal-stimulated jejunal absorption (P less than 0.001). These studies demonstrate distinct site specific variations in intestinal water and electrolyte absorption in both the basal and the meal-stimulated states.

Animals↗

Cholecystectomy. The impact of socioeconomic change.

The impact of our evolving health care system on a commonly performed surgical procedure, cholecystectomy, was assessed in a county-subsidized and private university hospital setting. Although condition on admission, use of resources, and outcome were unchanged in the private setting between 1980 and 1988, significant differences were noted among the largely uninsured patients at the county facility during this same time interval. There was a significant increase in the acuity of illness among patients undergoing cholecystectomy at the county hospital in 1988 as compared with 1980. These data suggest that alterations in reimbursement strategies and allocation of resources are significantly impacting on patient care, particularly in nonprivate health care facilities.

Adult↗

The application of positron emission tomographic imaging with fluorodeoxyglucose to the evaluation of breast disease.

Positron emission tomography (PET) is a computer-aided tomographic imaging technique that uses positron-emitting compounds to trace biochemical processes of tissue, and construct images based on them. The authors applied a whole-body PET imaging technique to patients with breast masses or mammographic abnormalities using the isotope 2-[F-18]-fluoro-2-deoxy-D-glucose (FDG), in a clinical trial to evaluate the feasibility of using PET to identify primary breast cancer, axillary lymph node involvement, and systemic metastases, before surgical resection. Fourteen patients have been entered on this study, 10 of whom proved to have breast cancer. Positron emission tomography correctly predicted the nature of 12 of the 14 primary breast lesions, and correctly determined the lymph node status of 11 of the 14 patients. The authors conclude that PET with FDG has potential as a diagnostic modality for detection of primary breast cancer, particularly in the patient with radiodense breasts by conventional mammography, and that it has potential for the preoperative identification of axillary lymph node metastases.

Adolescent↗