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Biomedical subjects

R J Greenstein

Publications and source records attributed to R J Greenstein.

At least 19 recordsLinked to original sources

Cholecystokinin upregulation during intestinal repair.

To determine whether cholecystokinin (CCK), a small intestinal hormone, may have autocrine or paracrine functions, gene regulation in the rat stomach and duodenum has been evaluated following cytotoxic injury. We quantified total RNA, CCK messenger RNA (mRNA), total protein, small and large forms of CCK peptides and gastrin. The stomach and the intestine respond differently. Following cytotoxic injury duodenal total RNA falls (1.5 +/- 0.1 vs 0.18 +/- 0.04 mg/g P less than or equal to 0.0001), and CCK mRNA content is depleted (260 +/- 23 vs 41 +/- 8 pg CCK mRNA/duodenum P less than or equal to 0.0001), yet there is a paradoxical increase in CCK mRNA concentration (176 +/- 20 vs 303 +/- 38 pg CCK mRNA/mg total RNA P less than or equal to 0.01). Increases occurred in both molecular species of CCK peptides evaluated: CCK8 (8 +/- 7 vs 26 +/- 2 pmole/g P less than or equal to 0.0001), large forms of CCK (42 +/- 4 vs 250 +/- 27 pmole/g P less than or equal to 0.0001). By contrast, in the stomach, only decreases were observed. These data identify sites of anatomical and biosynthetic upregulation during gastrointestinal repair. Changes are dependent upon the length of the period of recovery, differ between stomach and duodenum, and may be age related. Intestinal CCK may have para- and or autocrine roles in addition to its hormone function.

Animals

A computerized intensive care unit order-writing protocol.

OBJECTIVE: To present a computerized intensive care unit order-writing protocol. DESIGN: Descriptive report. SETTING: Eight-bed surgical intensive care unit, Department of Surgery, Department of Veterans Affairs Medical Center, Bronx, NY. METHODS: IBM-based, computer network program that provides user-friendly, logical, and comprehensive organ-system order sequences for patient management. RESULTS: Since July 1988, an order program that stresses (1) improved and more efficient patient care, (2) the use of program-integrated automatic safety features, (3) the substitution of computer entry for handwriting, and (4) the assurance that physicians deliver obligatory care in a logical organ-system-based progression has been implemented. CONCLUSIONS: The order protocol system presented is simple to introduce and operate, has minimal training and technical requirements, and is demonstrably reliable.

Computer Security

Mechanical retraction in laparoscopic surgery: cholecystectomy.

Mechanical retraction in laparoscopic surgery results in stable exposure, dependable field of vision, and more efficient use of personnel. The steps required to use mechanical retraction in laparoscopic cholecystectomy are outlined in this report.

Cholecystectomy, Laparoscopic

Postoperative hypertension: a multicenter, prospective, randomized comparison between intravenous nicardipine and sodium nitroprusside.

OBJECTIVE: To compare the efficacy and safety of iv nicardipine with sodium nitroprusside in the treatment of postoperative hypertension after both cardiac and noncardiac surgery. DESIGN: Multicenter, prospective, randomized, open-label study. SETTING: Six tertiary referral medical centers (recovery rooms and surgical ICUs). PATIENTS: A total of 139 patients with postoperative hypertension: i.v. nicardipine (n = 71), sodium nitroprusside (n = 68). INTERVENTION: Administration of i.v. nicardipine or sodium nitroprusside. MEASUREMENTS: Vital signs (BP, heart rate), hemodynamic variables, medication dosage, total number of dose changes, and time to achieve BP control were recorded. MAIN RESULTS: Both medications were equally effective in reducing BP in both the cardiac and noncardiac surgical groups. Under the conditions of the study, i.v. nicardipine controlled hypertension more rapidly than sodium nitroprusside (i.v. nicardipine 14.0 +/- 1.0 mins and sodium nitroprusside 30.4 +/- 3.5 mins, p = .0029). The total number of dose changes required to achieve therapeutic BP response was significantly less in the i.v. nicardipine-treated patients (i.v. nicardipine 1.5 +/- 0.2 vs. sodium nitroprusside 5.1 +/- 1.4, p < .05). Adverse effects were observed with both drugs (i.v. nicardipine 7% [5/71] and sodium nitroprusside 18% [12/68] [NS]). CONCLUSIONS: Intravenous nicardipine is as effective as sodium nitroprusside in the therapy of postoperative hypertension. Specific advantages have been identified. The use of i.v. nicardipine should be considered in the therapy of postoperative hypertension.

Aged

The brain-gut axis: a model system to study gene regulation.

The data summarized show unequivocal differences in gene regulation between the brain and the intestine in the rat. It is possible that the differences may occur partly as a reflection of cell turnover kinetics. The mechanisms accounting for these differences should provide fertile ground for investigation. I conclude that the brain-gut axis provides a model for studying differential gene regulation in animals.

Animals

Is aging preprogrammed? Observations from the brain/gut axis.

Age related differential gene expression occurs in the neuro-enteral axis. Brain and gut organ weight, total RNA, total protein and three peptides were quantified in 4-, 10- and 37-week-old Sprague-Dawley rats. As animals aged, total RNA decreased in the brain (0.65 +/- 0.3-0.28 +/- 0.03 mg/g), but remained stable in the gut (2.6 +/- 0.3-2.9 +/- 0.4 mg/g). Total protein concentration rose in the duodenum (612 +/- 28-734 +/- 34 mg/g), while levels remained stable in the brain (641 +/- 54-666 +/- 34 mg/g). Three peptides were studied, cholecystokinin (CCK), VIP and secretin. With increasing age, significant changes were found only in CCK a true neural-enteral peptide. The concentration of smaller molecular forms of CCK decreased in the brain (248 +/- 18-188 +/- 21 pmol/g), while they remained stable in the duodenum (33 +/- 2-36 +/- 3 pmol/g). By contrast, the concentration of the larger forms of CCK were stable in the brain (36 +/- 3-40 +/- 4 pmol/g), but rose in the gut (89 +/- 14-134 +/- 17 pmol/g). These data indicate that as rats age there is preprogrammed differential control of gene expression between brain and intestine.

Aging

Obesity surgery: expectation and reality.

Expectations and reality have been evaluated among 33 people considering, and 32 patients who had undergone, gastric restrictive surgery for morbid obesity. We addressed obesity history, dietary habits, expectations of surgery, weight loss, quality of life and obesity related diseases. Both groups had similar histories of a young age of onset and a strong family history of morbid obesity. Vomit avoidance was predominantly responsible for the highly significant decrease in total daily calories eaten (5283 +/- 356 vs 1622 +/- 95, P less than or equal to 0.0001). The ratios of carbohydrate, protein and fat, however, did not change. The desired weight loss was unrealistically high in both groups. Preoperative patients have unrealistic expectations concerning snack consumption. Postoperative patients have more realistic expectations concerning long term weight loss. Only 38 percent vs 70 percent of preoperative patients expected to lose 100-150 lbs (P less than or equal to 0.025). Disquietingly, 55 percent of preoperative and 41 percent of postoperative patients felt that weight loss following surgery is due to 'magic'. Percent excess weight loss for the postoperative patients was 61 +/- 9 percent from 4 to 84 months following surgery. Following weight loss there was the expected statistically significant improvement (P less than 0.001) in obesity related diseases. Long term follow-up (greater than or equal to 8 years) is now required to determine whether the changes following surgery for morbid obesity identified in this study will result in improvement of quality and/or length of life.

Dietary Carbohydrates

Postoperative sepsis: reexplore or observe? Accurate indication from diagnostic abdominal paracentesis.

OBJECTIVE: To determine if postoperative diagnostic abdominal paracentesis is a useful clinical tool in the abdominal evaluation of the critically ill septic patient. DESIGN: Retrospective review. SETTING: Surgical ICU patients in a Veterans Administration medical center. PATIENTS: Ten patients were studied from a total of 1,053 patients admitted to the surgical ICU between September 1985 and May 1989. INTERVENTIONS: Diagnostic abdominal paracentesis performed by the open or closed approaches. MEASUREMENTS AND MAIN RESULTS: Results are presented in three patient groups (A, B, and C): Group A (n = 4) had positive diagnostic abdominal paracentesis. Abdominal causes for the sepsis were found at reexploration. One of these four patients survived. Group B (n = 3) had negative diagnostic abdominal paracentesis. No abdominal septic source was found at reexploration; all three patients died. In group C (n = 3), diagnostic abdominal paracentesis was negative, patients were not reexplored, and all survived. Diagnostic accuracy correlated with three variables: a) the gross appearance and smell of the fluid, b) WBC count greater than 5000 or less than 500/mm3, and c) Gram stain demonstrating bacterial organisms. CONCLUSIONS: Diagnostic abdominal paracentesis proved accurate, reliable, simple, safe, and rapid in evaluating the abdomen in the postoperative septic patient. The use of this procedure should be considered in postoperative septic patients in whom an abdominal source for the sepsis needs to be excluded.

Adult

Differential cholecystokinin gene expression in brain and gut of the fasted rat.

Cholecystokinin (CCK) gene expression has been compared in the brain and duodenum of control and 5 days fasted rats. To study transcription, CCK mRNA was quantified using a solution hybridization assay. Large and small molecular weight CCK peptides were separated using a sequential extraction process and subsequently quantified by radioimmunoassay. In the duodenum, a fall in weight was paralleled by a decrease in CCK mRNA and in the large forms of CCK peptides. Small molecular species of CCK peptides did not change. There was no change in weight, CCK transcriptional or translational products in the brain as a whole. These data indicate location-specific differential regulation of the products of CCK gene expression in the fasted rat.

Animals

The effect of various postphlebotomy storage conditions on drug levels.

Monitoring drug levels in patients is standard practice in presentday critical care medicine. Clinical laboratories, however, are often unable to assay drug levels immediately following phlebotomy. This may result in blood samples being kept under a variety of storage conditions for nonuniform periods of time. The current study evaluated the stability of eight frequently monitored medications and one of their metabolities, in whole blood and plasma, at 4 degrees C or 25 degrees C, for up to 72 hours. The drugs included antibiotics, a bronchodilator, antiarrhythmics, and an anticonvulsant. Significant changes in drug levels were not identified at the time points studied. Our data suggests that meticulous postphlebotomy handling of blood samples may not be essential to obtain accurate levels of the drugs studied.

Animals

Constitutive attachment of murine erythroleukemia cell histone-depleted DNA loops to nuclear scaffolding is found in the beta-major but not the alpha 1-globin gene.

We have identified a region of the beta-globin gene that is attached constitutively to histone-depleted murine erythroleukemia cell nuclei. This region spans 800 bp and is located at -300 to -1100 bp upstream from the site of transcriptional initiation. Attachment is not altered by transcriptional activation of the beta-globin gene during induction to terminal differentiation, and the same region of the beta-globin gene is attached to histone-depleted myeloma cell nuclei (NS-1). The attached region contains an A/T-rich section, in addition to a sequence closely related to the Drosophila topoisomerase II consensus cleavage sequence. No comparable site of attachment of the alpha 1-globin gene was detected when a region spanning 1.5 kb 5' to 0.5 kb 3' of the region of transcription was studied.

Animals

Activation of the renin system in acute pancreatitis.

Activity of the renin-angiotensin system was assessed in patients with acute pancreatitis. Measurements of active plasma renin and inactive plasma renin were made in normal subjects, patients with acute pancreatitis, and patients with acute abdominal pain syndromes exclusive of pancreatitis. Active plasma renin values were significantly increased in acute pancreatitis, nearly 500 percent higher than in the other two groups. Inactive plasma renin values were similar in the three groups. In a subgroup of patients with acute pancreatitis, measurements were made on presentation and after recovery. The elevated active plasma renin values on admission fell significantly with recovery, in parallel with changes in serum amylase values. Inactive plasma renin values changed variably; there was a significant inverse regression relationship between the changes in active and inactive plasma renin values with recovery. The results indicate that the renin-angiotensin system is activated in acute pancreatitis to a significantly greater extent than in other syndromes with acute abdominal pain. The increased active plasma renin in acute pancreatitis is most likely due to renal release secondary to the reduced circulating volume and hypotensive effect of this disease. However, changes in the relationship between active and inactive plasma renin in some patients suggest that activation of inactive renin by proteolytic enzymes released in acute pancreatitis might play an additional role.

Abdomen

Distribution, molecular forms, and bioactivity of immunoreactive gastrin in a patient with metastatic gastrinoma.

A patient with metastatic gastrinoma whose plasma gastrin ranged from 7.6 nmol X ml-1 at presentation to 18.9 nmol X ml-1 just before death 4 yr later has been studied. The presence of such high circulating levels facilitated study of the biological and immunological activities as well as the molecular forms of gastrin in plasma, ascitic fluid, urine and cerebrospinal fluid. The results indicate: 1) the 34 amino acid gastrin (G34) was the only molecular form detectable in the body fluids studied; 2) bioactivity of G34 is maintained despite passage across the renal endothelium and the blood brain barrier; 3) the blood brain barrier significantly limits diffusion of G34.

Adult

Colonic vascular ectasias and aortic stenosis: coincidence or causal relationship?

Eleven patients with vascular ectasias of the colon and associated gastrointestinal hemorrhage were evaluated. All had the clinical features associated with aortic stenosis. In two patients, the configuration of the pulse wave in the mesenteric vessel was studied. In both, the abnormal peripheral pulse wave pattern associated with aortic stenosis was also transmitted to the ileocolic artery, where it differed quite clearly from the pattern in control patients. In a parallel study, the computer records of 3,623 patients with aortic or mitral stenosis admitted to the Mount Sinai Hospital over a 10 year period were reviewed for the presence of cryptogenic gastrointestinal hemorrhage. Twenty-one of 1,811 patients with aortic stenosis but only 1 of 1,812 patients with mitral stenosis had concomitant gastrointestinal hemorrhage (chi-square = 18, p less than 0.001). These data suggest that the cause of colonic vascular ectasias should be attributed to pathologic abnormalities of the arterial inflow pulse wave, rather than to chronic intermittent submucosal venous outflow obstruction.

Aged

Pathogenesis of precirrhotic portal hypertension in alcohol-fed baboons.

To study mechanisms and anatomic correlates of precirrhotic portal hypertension, we measured portal pressure either at laparotomy (in the portal vein) or by hepatic vein catheterization (wedge pressure) in 24 pairs of baboons fed 50% of energy either as ethanol or isocaloric carbohydrate (controls) for 4 mo-9 yr. On liver biopsy 7 had simple fatty liver; none had portal pressure exceeding the control range (2.7-13.0 cmH2O). The remaining 17 alcohol-fed baboons had fibrous tissue deposition around the terminal hepatic venules and adjacent sinusoids. The mean portal pressure was significantly increased (15.0 +/- 1.4 cmH2O) compared with the value in baboons with fatty liver (9.6 +/- 0.9 cmH2O) and in controls (8.0 +/- 0.6 cmH2O), with 8 animals exceeding the control range. Estimated hepatic blood flow was unchanged. Alcohol feeding resulted in increased hepatocyte size in both the fatty liver and fatty liver with fibrosis group; however, portal pressure did not correlate with alterations of cell size, liver volume, hepatic triacylglycerol, and protein contents. By contrast, for veins of comparable size, there was a significant correlation (r = 0.6666, p less than 0.01) between the thickness of the perivenular fibrous rim and portal pressure. Perivenular fibrosis was commonly associated with adjacent perisinusoidal fibrosis and this lesion also correlated with portal pressure. Furthermore, if one postulates that increased cell size causes enhanced pressure with secondary fibrosis, the latter should have first occurred "upstream," in the mid and portal zones. Sequential biopsy specimens, however, showed that fibrosis first appeared in the perivenular areas, suggesting that, in most instances, increased pressure is in fact secondary to the perivenular fibrosis.

Animals

Malignant schwannoma of the stomach in a patient with von Recklinghausen's disease.

A patient with von Recklinghausen's disease died with a malignant schwannoma of the stomach and was found at autopsy to have neurofibromatosis of the gastrointestinal tract, a plexiform neurofibroma of the myocardium and a phaechromocytoma. Malignancy of the gastrointestinal tract in von Recklinghausen's disease is rare, and this case highlights the difficulties in histological diagnosis of malignant nerve sheath tumours.

Adrenal Gland Neoplasms

The sphincter of Oddi, sphincterotomy and biliopancreatic disease.

The physiology and pathophysiology of the sphincter of Oddi are poorly understood. The relationships of functional disorders of the sphincter to biliary and pancreatic disease and of organic lesions of the papilla to pancreatic inflammatory disease are subjudice to say the least. The efficacy of sphincter section in the treatment of chronic pancreatitis is unproved. Section of the sphincter may be necessary to treat biliary tract pathology but its use should not be routine or indiscriminative since, there is morbidity as well as mortality. Finally, the price of sphincterotomy is: 1. hemorrhage; 2. duodenal perforation; 3. pancreatic duct damage--a. acute pancreatitis; b. chronic pancreatitis; 4. sphincter incompetence--a. common duct regurgitation--cholangitis; b. pancreatic duct regurgitation--pancreatitis; 5. sphincter stenosis--obstructive jaundice; 6. stasis cholecystitis; 7. diarrhea; 8. morbidity 10%; 9. mortality 1.9%.

Ampulla of Vater