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Biomedical subjects

J R Starling

Publications and source records attributed to J R Starling.

At least 55 records · Page 3Linked to original sources
PubMed1985

Reduced incidence of rat colon cancer metastases by perioperative immunostimulation with maleic anhydride-divinyl ether-2 (MVE-2).

Intra-abdominal operations result in profound immunodepression during a period when tumor cells are released into the systemic and portal circulations. This combination may augment tumor metastases. The authors have developed a model in which rat colon carcinoma cells transplanted into the portal vein consistently induce hepatic metastases by four weeks, and death within nine weeks. Additionally, the authors have shown that perioperative treatment with levamisole significantly reduces the incidence of metastases. This study tested whether maleic anhydride-divinyl ether-2 (MVE-2), a known immunostimulant, would produce similar effects. Rats pretreated with MVE-2 the day before and day of tumor implantation developed fewer metastases (34 percent of animals treated with MVE-2, compared with 5 percent of animals not treated with MVE-2 had less than or equal to two liver metastases). Eighteen percent of MVE-2-treated rats developed no hepatic metastases. Comparison of median liver weights between the MVE-2-treated group and the nontreated, tumor-bearing group was significant (P = 0.03) and the MVE-2-treated animals had significantly prolonged survival (P = 0.04). The authors conclude that the perioperative period is critical for the implantation and growth of metastases and that perioperative immunostimulation may be a factor in decreasing the incidence of metastases. This model may have relevance to the adjuvant treatment of human colonic cancer.

Adenocarcinoma↗
PubMed1985

Lysosomal enzyme activity in pulmonary alveolar macrophages, peritoneal macrophages, and blood mononuclear leukocytes in the hypothyroid rat.

Chronic hypothyroidism can result in an increased susceptibility to severe pulmonary or genitourinary tract infections. We postulate that decreased lysosomal activity in the pulmonary alveolar macrophage (PAM), peritoneal macrophage, and mononuclear leukocyte may be a factor which results in the impaired response to infections in hypothyrosis. In this study rats underwent total thyroidectomy and had their PAMs, peritoneal macrophages, and mononuclear leukocytes analyzed after 4, 8, and 12 weeks. The total lysosomal activity (postnuclear homogenate + lysosomal-rich cell fraction) of PAMs was 50% of age-matched controls. Peritoneal macrophage lysosomal enzyme activity was 25-30% of control activity. In separate experiments, rats were administered physiologic replacement of triiodothyronine (T3) 8 weeks after thyroidectomy. This resulted in PAM and peritoneal macrophage lysosomal enzyme activity similar to control activity. Mononuclear leukocyte lysosomal enzyme activity from hypothyroid rats showed decreases in only one of the three enzymes monitored (beta-glucuronidase). Hypothyroidism did result in a decrease in total number of mononuclear leukocytes harvested per animal. Administration of T3 resulted in mononuclear leukocyte beta-glucuronidase activity similar to euthyroid rats (44 +/- 8 U/mg protein vs 42 +/- 3 U/mg protein). In summary, hypothyroidism in the rat results in decreases in subcellular lysosomal enzyme activity in PAMs, peritoneal macrophages, and mononuclear leukocytes.

Animals↗
PubMed1985

Pulmonary pathophysiological changes in sheep caused by endotoxin precursor, lipid X.

The chemical structure of the biologically active lipid A portion of Gram-negative endotoxin [lipopolysaccharide (LPS)] has recently been elucidated. This was greatly facilitated by the isolation of an Escherichia coli mutant that accumulates large quantities of lipid X, a novel monosaccharide precursor of lipid A (C. R. H. Raetz, Rev. Infect. Dis. 6: 463-471, 1984). We now report on the activity of lipid X in the lung-lymph model in sheep. We have measured the response to cumulative bolus injections of lipid X (2,3-diacylglucosamine 1-phosphate) in six chronically instrumented unanesthetized sheep. Lipid X at a total dose of 40 micrograms/kg produced a biphasic pattern of changes. The early phase was characterized by a rapid transient pulmonary arterial constrictive response that was dose dependent, accompanied by a delayed transient increase in lung-lymph flow (P less than 0.05), a significant (P less than 0.01) decrease in arterial blood O2 tension and an increase (P less than 0.05) in lung-lymph protein clearance. Protein permeability changes in the first phase are not usually seen following endotoxin injection. However, like endotoxin, lipid X also produced a late phase (3-6 h later) of increased lung vascular permeability to fluid and protein as reflected by significant (P less than 0.05) increases in both lung-lymph flow and lung-lymph protein clearance in the presence of stable pulmonary vascular pressures at or below base-line levels. We conclude that some of the pulmonary pressor activity of the endotoxin molecule can be attributed to the lipid X substructure. Furthermore, changes in vascular permeability may also be initiated by this substance.

Animals↗
PubMed1984

Diagnosis and management of genitofemoral neuralgia.

Genitofemoral neuralgia is a syndrome characterized by chronic pain and paresthesia in the region of genitofemoral nerve distribution. Genitofemoral nerve entrapment has been described after inguinal herniorrhaphy, appendectomy, and cesarean section. Failure to distinguish it from ilioinguinal nerve entrapment can result in unnecessary inguinal reexploration, or patients severely debilitated from chronic pain. We recommend that patients with persistent pain and paresthesia in the inguinal region following surgery should have a local ilioinguinal nerve block. If this is unsuccessful in affecting relief of symptoms, a paravertebral block of L-1 and L-2 should be considered. Using these two blocks, a rational decision can then be made to operate on either the ilioinguinal nerve or the genitofemoral nerve. We describe three cases of genitofemoral neuralgia treated by extraperitoneal excision of the genitofemoral nerve.

Adult↗
PubMed1984

Lysosomal enzyme release in hypothermically perfused dog kidneys.

This study investigated lysosomal disruption during hypothermic perfusion preservation of kidneys and its possible relationship to viability. The percentage of free and bound enzyme activity was analyzed for three lysosomal enzymes in homogenates made from perfused canine kidney cortex tissue, including beta-glucuronidase, cathepsin-D, and aryl sulfatase. All three enzymes displayed characteristic increases in free enzyme activity (47-68%) throughout 5 days of perfusion preservation. The increased activity obtained at 5 days of preservation was found to indicate "severe" tissue damage, as shown by a similar increase obtained in renal cortex tissue exposed to warm ischemia (37 degrees C) for 4 hr or longer. Aryl sulfatase was found to be the most sensitive indicator of severe damage. Pretreatment of kidney donors with methylprednisolone, a lysosomal stabilizer, was also studied in kidneys exposed to 5 days of perfusion. Pretreatment was found to reduce the percentage of free lysosomal enzyme activity following 5 days (nonviable) of perfusion to those levels normally obtained following 3-day (viable) perfusion. This indicates that methylprednisolone may be useful in modulating the severe disruption of lysosomes induced by long-term preservation. It is concluded that extensive disruption of lysosomes occurs during hypothermic perfusion preservation and may represent one cause for loss of organ viability.

Animals↗
PubMed1984

Cancer surveillance after ureterosigmoidostomy: colonic microscopic changes.

Ureterosigmoidostomy (U-S) is a procedure for diversion of the urinary stream. U-S is associated with a manyfold-increased risk for subsequent development of colonic carcinoma close to the sites of ureteral entry into the sigmoid colon. A surveillance program for colonic carcinomas in U-S patients includes colonoscopic examination of the colon to at least 60 cm and random biopsies of the sigmoid colon distal to the ureteral orifices. In eight patients, a change from sulphomucin to a variable admixture with sialomucin was found in the histologically unremarkable colonic mucosae. When the urinary stream was shunted away from the U-S site in two patients, the mucosal mucin was composed of sulphomucin which is present in normal sigmoid colons. The effect of urine admixed with feces in the sigmoid colon is nonspecific as judged by alterations of the mucosal mucin composition. The U-S patient deserves periodic examinations to detect colonic carcinoma but the histological examination of colonoscopically unremarkable mucosae is not currently contributory toward this surveillance effort.

Adult↗
PubMed1984

Thyroid lysosomal enzyme activity and ultrastructure after subtotal thyroidectomy.

Subtotal thyroidectomies were performed in rats to increase the level of endogenous TSH, creating a condition of chronic TSH stimulation. The activities of various classes of lysosomal enzymes (cathepsin D, beta-glucuronidase, and aryl sulfatase A) were studied in thyroid tissue remaining in situ at various time intervals after subtotal thyroidectomy (sub-tx). These alterations were correlated with morphometric and ultrastructural changes in tissue lysosomes and with serum T4 and TSH. Specific activities of all three lysosomal enzymes were elevated in the residual tissue as compared with those in control tissue during 7 weeks after sub-tx in the first experiment. In the second experiment, the activities of all three enzymes were elevated both 3 and 6 weeks after sub-tx, and the activities of cathepsin D and aryl sulfatase A in the postnuclear homogenate (S2) were significantly elevated. Plasma TSH was elevated and T4 was decreased both 3 and 6 weeks after sub-tx. The results of the third experiment determined that there were significant alterations in nuclear cytoplasmic ratios as well as in the number, area, and volume density of lysosomes in both groups compared with respective control values. In addition, both lysosomal area and volume density in animals 6 weeks after sub-tx were significantly larger than those in animals 3 weeks after sub-tx. We conclude that chronic stimulation of residual thyroid tissue 6 weeks after sub-tx causes alterations in lysosomal ultrastructure as well as in lysosomal enzyme activity.

Animals↗
PubMed1984

Control of bleeding esophageal varices by transabdominal esophageal transection, gastric devascularization, and splenectomy.

Between November 1980 and October 1982, 11 patients underwent modified Sugiura procedures (esophageal transection, gastric devascularization, and splenectomy) for bleeding esophageal varices, with an operative mortality of 36%. One patient rebled at 2 months and was successfully managed by sclerotherapy. Intraoperative portal pressure fell approximately 25% after splenectomy. We contend that esophageal transection and gastric devascularization provide good short-term control of bleeding varices, and that the decrease in portal pressure provided by splenectomy allows scars to form during a period of reduced portal pressure, providing long-term arrest of variceal hemorrhage.

Adult↗
PubMed1984

Prevention of rat colon cancer metastases by perioperative immunostimulation.

Major intra-abdominal operations result in profound immunodepression. In addition, manipulation of malignant tumors may release tumor cells into the systemic and portal circulations. The additive effects of immunodepression and tumor cell release may enhance the metastatic potential of tumors. Perioperative correction of immune depression by levamisole can restore lymphocyte proliferation levels in rats. We have developed a model in which rat colon carcinoma cells transplanted into the portal venous system consistently induce hepatic metastases by 4 weeks and death within 9 weeks. Rats pretreated with levamisole (4 mg/kg administered intraperitoneally) the day before and the day of tumor implantation developed fewer metastases (41% of animals treated with levamisole compared with 6% of animals not treated with levamisole had less than or equal to two metastases per liver). Twenty percent of the rats treated with levamisole developed no hepatic metastases. Comparison of median liver weights between the group treated with levamisole and the nontreated, tumor-bearing group was highly significant (p less than 0.005). We conclude that the perioperative period is critical for the implantation and growth of metastases and that perioperative immunostimulation may be a factor in decreasing the incidence of metastases. This model may have relevance to the adjuvant treatment of human colon cancer.

Adenocarcinoma↗
PubMed1984

Value of colonoscopy after ureterosigmoidostomy.

Ureterosigmoidostomy (US) is an acceptable procedure for urinary diversion. Despite problems with ascending pyelonephritis, anal incontinence, and recently a reported 100- to 500-fold increase in the incidence of colonic carcinoma, the popularity of US is predicted to increase. The records of 110 patients who have undergone US at our institution have been reviewed. Invasive colon cancer developed at the site of ureter implantation in three of these patients. All patients had rectal bleeding and obstipation as initial symptoms. We have located 17 of our US patients and all consented to colonoscopy and urologic follow-up. At colonoscopy 41% of these patients had one to three polyps (0.5 to 6 cm) involving or near the site of the US. No polyps were seen proximal to the US sites. Polyps were histologically defined as tubovillous adenomas or mixed tubovillous-transitional cell adenomas. A single patient with three 4 to 6 cm polyps had superficial adenocarcinoma found in two of the polyps. Recurrent polyps or dysplasia has not been found on follow-up examination. Despite the disadvantages of US, the likely increased popularity of this procedure mandates that all patients be followed regularly for polyps and cancer. Our data support the following recommendations: (1) surveillance colonoscopy should be started soon after US, and (2) conversion to an alternative diversion should be made if recurrent polyps, cancer, or dysplasia is found. Yearly colonoscopy and screening for occult blood must be part of the comprehensive follow-up on all patients after US.

Adenocarcinoma↗
PubMed1983

Colon carcinoma metastatic to the ovary.

We reviewed 17 patients with colon carcinoma metastatic to the ovary seen from 1970-1980. This represents 2.5% of the total malignant ovarian neoplasms seen during this time period. In 3/17 patients, exploratory celiotomy was performed without preoperative barium enema, stool for occult blood, or colonoscopy. These patients subsequently were found to have a primary colon carcinoma. Colectomy was performed in 8/17 of our patients without prophylactic oophorectomy. All of these patients subsequently developed metastatic ovarian carcinoma. Long-term survival in our series was dismal. We recommend (1) a compulsary colon examination to include colonoscopy prior to surgery for ovarian masses, and (2) prophylactic bilateral salphingo-oophorectomy at the time of colectomy for colon carcinoma.

Adult↗
PubMed1983

Tumor specific reactivity during development of N-methyl-N-nitrosourea-induced rat colon cancer.

Invasive colon adenocarcinomas with lymph node metastases can be induced in Sprague-Dawley rats by 15 weekly intrarectal injections of 2 mg N-methyl-N-nitrosourea (NMU). Extracts were prepared from invasive adenocarcinomas and normal rat colon mucosa by a 2 phase gradient. Mixed leukocyte tumor interaction (MLTI) assays stimulating lymphocytes from tumor-bearing and normal rats were performed using these extracts. Quadruplicate cultures were established with 2 X 10(5) lymphocytes and tumor or normal colon extract. Cultures were pulsed with H3 thymidine at 7 days and harvested 6 hours later. Results were expressed as net counts (experimental CPM minus background CPM). Reactivity in tumor-bearing animals was first seen when rat colons showed intraepithelial dysplasia histologically and was maximal when early invasive colon tumors were present. No difference in stimulation was seen between tumor-bearing and normal animal lymphocyte reactivity with normal colon extract. In conclusion, animals with NMU-induced rat colon cancer show specific tumor reactivity in MLTI assays. Immune reactivity in these animals may provide clues to clinical tumor status by immunologic assay.

Animals↗
PubMed1983

Development of a carcinogen-induced rat colon cancer with lymph-node metastases.

The progression from normal colonic mucosa to invasive adenocarcinoma of the colon with lymph-node metastases was documented in Sprague-Dawley rats receiving 30 mg of N-methyl-N-nitrosourea via intrarectal injections. Histologically, these tumors closely resemble human colonic cancer. This model is predictable and reproducible. It offers a genetically nonidentical rat model for the development of cancer biology and therapy models.

Animals↗
PubMed1983

A lysosomal study of cold-induced hyperthyroidism in the rat: comparison to human hyperthyroid tissue.

Prolonged exposure to cold in the adult rat is considered an acceptable model to study experimental hyperthyroidism. In our experiments adult rats were exposed to cold (1 degree to 4 degrees C) for various periods of time, after which their thyroid tissue and plasma were assayed for lysosomal enzyme activity. In additional animal experiments we examined the cold-exposed rats during propranolol treatment. After 2 weeks of exposure to cold, rat thyroid glands were hypertrophied and hypervascular. There was a significant increase in all three lysosomal enzymes measured in the rat thyroid tissue compared to age-matched controls. The percent of enzyme activity found in the various subcellular fractions did not change. The plasma triiodothyronine concentration increased slightly in the cold-exposed rats, whereas there was no change in thyroxine or lysosomal activity. Propranolol had no effect. In separate experiments human thyroid tissue from patients with diffuse toxic goiter or histologically normal thyroid tissue was examined. Similar to cold-exposed rat thyroid tissue, diffuse toxic goitrous tissue showed a twofold to threefold increase in lysosomal enzyme activity compared to control tissue. These data suggest that increased thyroidal lysosomal enzyme synthesis is one of the factors operative in the increased secretion of active thyroid hormones in Graves' disease.

Animals↗
PubMed1983

Shunts for portal hypertension.

Eighty-nine patients underwent 95 portasystemic shunts for portal hypertension at our institutions between June 1963 and March 1981. Ninety-three shunts were performed for bleeding varices. Procedures that were performed included 11 Warren shunts, 29 Linton shunts, 28 interposition mesocaval shunts, 26 classic portacaval shunts, and one umbilical to saphenous vein shunt. Thirty-six shunts were performed in Child class A patients (5.5% operative mortality), 37 in Child class B (16.2% operative mortality), and 22 in Child class c patients (36.3% operative mortality). Five-year survival for Child A patients was 74 per cent, 17.4 per cent for Child B patients and 26.3 per cent for Child C patients. Twelve of 14 patients (15.7%) who had recurrent postoperative upper gastrointestinal bleeding were found to have occluded shunts (two Warren, six Linton, one mesocaval, and three portacaval). Of 21 patients who became encephalopathic postoperatively, 17 had alcoholic liver disease. In 15 of these alcoholic patients who survived the immediate postoperative period, encephalopathy correlated directly with continued alcohol consumption. Several conclusions can be drawn from our data: portasystemic shunts can be performed with acceptable morbidity and mortality; rebleeding generally indicates shunt occlusion; encephalopathy can be correlated with continued alcohol consumption after shunting; there appears to be little difference in survival and rebleeding in the various shunt procedures; the poor survival figures for Child B and C patients must make one seriously consider alternative procedures in these poor-risk candidates.

Encephalitis↗
PubMed1983

Treatment of nontoxic megacolon by colonoscopy.

The indications for colonoscopy in a recent consecutive series of 232 examinations were analyzed. Of these examinations, 30 (13%) were performed for nontoxic megacolon. Nontoxic megacolon is defined as severe dilatation of a segment or the entire colon unaccompanied by signs or symptoms of colon toxicity. Mechanical factors (volvulus, anastomosis, diverticulosis, carcinoma) were responsible for the nontoxic megacolon in 13 of these patients. Nontoxic megacolon was classified as secondary to acute pseudoobstruction (Ogilvie's syndrome, pancolonic megacolon, acute myxedema ileus) in 17 patients. All patients were being evaluated for possible exploratory celiotomy to prevent perforation of the colon because of the massive colonic distention. Colonoscopic examination was performed at the bedside or in the intensive care unit for 11 of 30 patients. No bowel preparation was used. Evacuation of air and fecal material was more efficiently accomplished by use of an external suction device attached to the biopsy part of the endoscope. For 12 of the 13 patients who had a mechanical basis for their nontoxic megacolon the colon was successfully decompressed. All 17 patients with acute pseudoobstruction were successfully treated. There were no iatrogenic perforations. Possible emergency operation was avoided for all patients except one who had a cecal volvulus. Colonoscopy should be considered as the initial treatment for nontoxic megacolon prior to surgical intervention.

Colonoscopy↗