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Biomedical subjects

E A Woltering

Publications and source records attributed to E A Woltering.

At least 55 records · Page 3Linked to original sources
PubMed1992

Effective palliative treatment of metastatic carcinoid tumors with intra-arterial chemotherapy/chemoembolization combined with octreotide acetate.

Survival in patients with metastatic carcinoid tumors is dependent on control of tumor growth and adequate palliation of vasoactive amine-induced symptoms of flushing, diarrhea, wheezing, and valvular heart disease. Eight patients with carcinoid tumors metastatic to the liver were treated with long-term octreotide acetate therapy (100 to 500 micrograms three times a day), intra-arterial 5-fluorouracil infusion (2 g/day x 5 days), and hepatic tumor chemoembolization. All eight patients became asymptomatic and have remained so with a mean follow-up duration of 22 months from the time of first infusion. Following institution of subcutaneous octreotide acetate, intra-arterial infusion, and tumor chemoembolization, all patients are alive with a mean survival of 40 months from the time of diagnosis of carcinoid syndrome (range: 2 to 108 months). Four patients had greater than a 50% decrease in tumor size after therapy (mean follow-up duration: 10.6 months), and the other four patients have had stable disease after institution of therapy. It appears that combinations of long-term subcutaneous administration of octreotide acetate, intra-arterial 5-fluorouracil, and tumor chemoembolization effectively control progressive liver metastasis and provide excellent symptomatic palliation in patients with hepatic metastasis from functional carcinoid tumors.

Carcinoid Tumor↗
PubMed1992

DMSO protects against adriamycin-induced tissue necrosis.

Inadvertent extravasation of Adriamycin (Adria) can result in severe tissue necrosis. The mechanism of this tissue damage is believed to be the release of free radicals into the tissue. Topical applications of dimethylsulfoxide (DMSO) used after Adria extravasation have been shown to decrease ulcer size. This may be due to DMSO's ability to scavenge free radicals. However, effective topical therapy requires prompt recognition of extravasation, which is often difficult. We hypothesized that the delivery of Adria in low concentrations DMSO would reduce Adria-induced ulcer size and ulcer incidence caused by Adria extravasation. To test this hypothesis, 180, male Sprague-Dawley rats were randomly allocated into three treatment groups of 60 each. All three groups received intradermal injections of Adria (1 mg) diluted in 0.5 cc of saline (Group 1), 10% DMSO (Group 2), or 20% DMSO (Group 3). Rats were observed for 4 weeks. Ulcer incidence (%) and size of ulcers (mm2) were assessed over time. Area of skin ulceration was calculated as the product of the two greatest diameters. Statistical evaluation of the differences in incidence and ulcer size between Group 1 and Groups 2 or 3 were evaluated using analysis of variance. Delivery of Adriamycin in 10 or 20% DMSO resulted in a statistically significant (P less than 0.001) decrease in the incidence of ulceration caused by intentional Adria extravasation.

Animals↗
PubMed1992

Synergistic cytotoxicity of combinations of dimethyl sulfoxide and antineoplastic agents against P388 leukemia in CD-F1 mice.

We have reported that dimethyl sulfoxide (DMSO) and antineoplastic agents exhibit synergistic cytotoxicity against human tumors in vitro. This study was undertaken to investigate this effect in vivo. Groups of mice were given intraperitoneal (i.p.) injections of P388 leukemia cells. Groups were treated with i.p. injections of either saline, DMSO alone, mitoxantrone hydrochloride (DHAD) alone, methotrexate alone, DHAD in DMSO or methotrexate in DMSO. Combinations of DMSO and DHAD produced 46-61% increases above expected survival, demonstrating synergistic cytotoxicity in vivo. Following confirmatory animal studies, trials utilizing i.p. delivery of antineoplastics in DMSO as treatment for peritoneal tumors should be undertaken.

Animals↗
PubMed1991

Somatostatin analogues inhibit angiogenesis in the chick chorioallantoic membrane.

The mechanism responsible for alterations in tumor growth following administration of somatostatin analogues is unknown. Somatostatin analogues, SMS 201-995 and RC-160, have demonstrated the potential to inhibit both tumor growth and vascularity, in vivo and in vitro. We hypothesized that SMS and RC-160 inhibit angiogenesis and this inhibition may alter tumor growth. To test this hypothesis, 2 mm methylcellulose disks containing concentrations of SMS 201-995 and RC-160 at 0, 0.5, 2.5, or 50 micrograms per disk, were implanted on the chorioallantoic membrane (CAM) of 6- to 7-day-old shell-less chick embryos. Inhibition of blood vessel growth in the region of the disk was visually assessed 24-36 hr following disk implantation and graded (0-4) based on the radius of the zone of inhibition from the center of the disk. The overall incidence of inhibition for the somatostatin analogues at concentrations of 0.5, 2.5, and 50 micrograms per disk was 13, 56, and 61% for SMS and 27, 49, and 68% for RC-160, respectively. Overall incidence of inhibition for the positive (inhibitory) control was 70.5% and those for buffer (negative) controls were 3-14%. Somatostatin analogues were associated in a dose-related fashion with both a greater percentage of inhibition of blood vessel growth and an increased grade of inhibition. Inhibition of angiogenesis may be a mechanism responsible for the tumor regression observed in vivo following SMS or RC-160 therapy.

Allantois↗
PubMed1991

Non-endocrine applications of somatostatin and octreotide acetate: facts and flights of fancy.

Somatostatin, originally detected by Krulich and ultimately isolated by Brazeau, was initially described as a growth hormone release-inhibiting factor. Subsequent investigation into the use of native somatostatin and the development of long-acting somatostatin analogues, especially octreotide acetate, have fostered increasing uses of these compounds. Though the clinical and investigational uses of somatostatin and its analogues are varied, one central theme remains constant: the ability of these agents to suppress circulating peptide levels. This article, a review of the current non-endocrine applications of somatostatin and its analogues, covers a wide range of potential applications for somatostatin-like compounds. These include use in cirrhosis and variceal bleeding, peptic ulcer disease, pancreatic fistulas, acute and chronic pancreatitis, dumping syndrome, cancer therapy, small bowel fistulas, psoriasis, pain control, and autonomic hypotension. Somatostatin may also play a role in the development and potential treatment of neurologic disease and may have profound found influence on behavior.

Digestive System Diseases↗
PubMed1991

Acute gastric pH changes alter intraluminal but not plasma peptide levels.

Gastric acidity is influenced by systemic and local peptide effects. Previous work by others has shown that intraluminally secreted peptides may have a role in local control of gastric acidity; however, the response of these peptides to acute changes in gastric pH is unknown. To determine the effects of acute changes in pH on systemic and intraluminal peptide levels, 14 normal volunteers underwent placement of a nasogastric tube after an overnight fast. Blood and gastric fluid were analyzed on a control day, 2 hours after completion of 24 hours of aluminum-magnesium antacid therapy and after 24 hours of H2 blockade. Plasma and acid-alcohol-extracted gastric peptide levels were measured with specific radioimmunoassays. Specimens were subdivided into two groups: 28 gastric fluid specimens with a pH less than 4 and 10 specimens with a pH greater than 4. In the patients with a pH greater than 4, the luminal peptides, motilin, neurotensin, pancreatic polypeptide, somatostatin, substance P, and gastrin, were decreased by 50% to 90% and gastrin-releasing peptide was decreased by 36% compared with specimens with a pH less than 4. Conversely, intraluminal vasoactive intestinal polypeptide and calcitonin levels were elevated by 60% and 27%, respectively, in the samples with a pH greater than 4. Intraluminal peptide concentrations are responsive to changes in intragastric pH; however, this response was not seen in plasma peptide levels.

Antacids↗
PubMed1990

Treatment of nonendocrine gastrointestinal disorders with octreotide acetate.

Somatostatin and its longer-acting analog, octreotide acetate, can be used effectively for the treatment of nonendocrine gastrointestinal disorders. Octreotide has been shown to decrease pancreatic fistula output by suppressing exocrine pancreatic function. We believe that octreotide acetate may be useful to prophylaxis against the development of pancreatic fistulas following pancreatic resection and may reduce the enzymatic and volume output of established pancreatic fistulas. We also have shown that administration of octreotide acetate 2 hours before a high carbohydrate test meal reduces gut peptide levels, which increase following meal ingestion in patients with the dumping syndrome. Reduction of circulating peptides in these patients may slow gut motility and improve glucose regulation, thus, providing relief of postvagotomy dumping symptoms.

Dumping Syndrome↗
PubMed1990

Effect of somatostatin analog on peptide release and tumor growth in the Zollinger-Ellison syndrome.

The clinical presentation of Zollinger-Ellison syndrome (ZES) is the result of gastrin hypersecretion and may be modified by secondary peptide hypersecretion. Treatment is medical (H2-blockers) or surgical (tumor excision and total gastrectomy). H2-blocker escape occurs up to 23 per cent and surgical mortality ranges to 15 per cent. Treatment of advanced disease has limited success. Sandostatin (SMS 201-995) has been shown to decrease basal gastrin and gastric acid secretion in ZES. We hypothesized that SMS would suppress basal and provoked gastrin and secondary peptide secretion in ZES. A patient with refractory, metastatic gastrinoma underwent provocative testing (test meal, calcium infusion, secretion bolus and tolbutamide bolus). Thirteen peptides were drawn at set intervals during these provocative tests. Testing was repeated during SMS therapy (100 micrograms subcutaneously three times per day). Gastrin, pancreatic polypeptide (PP) and glucagon levels were elevated at baseline. SMS suppressed all three peptides (mean 74 per cent) (p less than 0.05). Gastrin, PP and glucagon were provoked by all four tests (means above baseline, 19, 155 and 138 per cent, respectively). Gastrin-releasing peptide, gastric inhibitory peptide and insulin were provoked by calcium infusion (427, 306 and 162 per cent above baseline, respectively). SMS suppressed 14 of 15 of these peaked-provoked peptide levels (mean 72.5 per cent, p less than 0.05). Gastric analysis during calcium infusion showed SMS suppression of hourly gastric secretory volume by 77.5 per cent and of acid production (milliequivalents of acid) by 87.5 per cent. During a 20 month follow-up period, the patient was maintained on SMS, 200 micrograms subcutaneously three times per day. She has remained asymptomatic. Interval peptide profiles at two, eight and 18 months show normal gastrin, PP and glucagon levels. A computed tomographic scan at eight months shows a remarkable regression of primary and metastatic tumor. Regrowth, however, was noted at 19 months. SMS may be useful in ZES by suppressing basal and provoked gastrin and secondary peptide secretion and may occasionally give palliation by yielding temporary tumor registration.

Aged↗
PubMed1990

Adult onset nesidioblastosis: response of glucose, insulin, and secondary peptides to therapy with Sandostatin.

Adult onset nesidioblastosis (AON) is an extremely rare entity associated with hypersecretion of insulin. Previous reports have demonstrated that the somatostatin analog, Sandostatin (SMS), will control the clinical symptoms induced by infantile nesidioblastosis. We hypothesized that insulin, C-peptide, and secondary peptide secretion from AON is provocable. We also hypothesized that SMS would suppress both basal and provoked primary and secondary peptide secretion in AON. To test this hypothesis, in a patient with AON, 13 gut peptide levels were determined at set intervals during provocative testing with a test meal, a calcium infusion, a secretin bolus, and a glucagon bolus. These tests were repeated under the influence of SMS. Insulin, C-peptide, and pancreatic polypeptide (PP) levels were elevated in the basal state. SMS suppressed all three peptides (mean 68%) (p less than 0.05). Basal fasting glucose rose by 65%, and glucose ratios were raised throughout all four tests. Insulin:glucose ratios decreased during SMS therapy. Insulin and PP secretion was increased by all four provocative tests (mean 458% and 665% above baseline, respectively). C-peptide was provoked by three tests (mean 204%). Peptides with normal basal values were also provocable. GRP and glucagon were provoked by secretin stimulation (182%, 186%, respectively). Calcium infusion stimulated CIP release by 372%. SMS suppressed the peak provoked peptide levels in all positive provocation tests (p less than 0.05). Peak provoked insulin values were decreased by 59%, C-peptide by 75%, and PP by 92%. Peak provoked glucagon, CRP, neurotensin, and GIP levels were decreased by 20%, 65%, 51%, and 73%, respectively. The patient has been maintained on SMS (25 micrograms bid) for 1 yr and has shown decreased insulin levels, normal glucose levels, and, at 1 yr, leads an asymptomatic normal life. SMS is able to suppress primary and secondary peptide secretion in both the fasting and provoked state. The long-term efficacy of SMS may be predicted by its ability to suppress primary peptide release during peak provocation.

Aged↗
PubMed1989

Effect of octreotide acetate on pancreatic exocrine function.

Somatostatin and its analogs have been shown to inhibit both pancreatic endocrine and exocrine function. We hypothesized that octreotide acetate (Sandostatin), a somatostatin analog, decreases the pancreatic flow rate through a peptide-mediated mechanism and alters pancreatic fluid composition by inhibiting carbonic anhydrase action and circulating peptide levels. To test this hypothesis, we collected pancreatic fluid from six patients (four with pancreatic fistulas and two with pancreatic drains after pancreatic resection). Pancreatic fluid volume and chloride, sodium, potassium, amylase, lipase, and bicarbonate levels were measured before and after octreotide acetate therapy. Octreotide acetate reduced pancreatic fluid output by a mean of 75 percent (p less than 0.05), increased chloride concentration by 21 percent (p less than 0.05), and reduced bicarbonate content by 45 percent (p less than 0.05). Sodium levels were unchanged, but the potassium concentration was increased by 14 percent (p less than 0.05). Total amylase and lipase production per 24 hours was decreased by 63 percent and 27 percent, respectively (differences not significant). Somatostatin may be useful in the treatment of established pancreatic fistulas and may be a useful prophylactic tool to prevent postoperative fistula formation.

Adult↗
PubMed1989

Sodium oxalate corrects calcium interference in Lowry protein assay.

We have previously noted that high levels (10 mM) of calcium interfere with protein determination in the Lowry assay. While there are numerous reports in the literature of substances interfering with the Lowry assay, none of these interfering substances are as ubiquitous as calcium. We hypothesized that physiologic levels of calcium may interfere with the protein determination as measured by the Lowry assay. To test this hypothesis, bovine serum albumin standards from 12.5 to 1600 micrograms/ml were tested in the Lowry assay in the presence of calcium chloride concentrations from 0 to 5 mM. In low protein concentrations (12.5-50 micrograms/ml) 1 to 2 mM calcium induced errors of up to 384%. In samples containing 100 to 400 micrograms/ml protein, 1 to 2 mM calcium induced errors of up to 40%. The addition of sodium oxalate to calcium-spiked protein samples significantly reduced the errors in protein determination at all calcium concentrations tested. This effect also is seen throughout the range of protein concentrations tested (50-1600 micrograms/ml). In most cases sodium oxalate pretreatment of samples used in the Lowry assay reduces errors by 70-95%. Physiologic levels of calcium induce significant errors in the estimation of protein concentration using the Lowry method. Routine pretreatment of Lowry samples with sodium oxalate will provide a more accurate estimation of the protein concentration in biological systems.

Animals↗
PubMed1988

Use of polar solvents in chemoprevention of 1,2-dimethylhydrazine-induced colon cancer.

To examine the effect of the polar solvents on 1,2-dimethylhydrazine (DMH)-induced colon cancer, 100 male Sprague-Dawley rats were randomly allocated to a control and three treatment groups. Treated animals received N-methylformamide (NMF), dimethylsulfoxide (DMSO), or methylsulfonylmethane (MSM) added to drinking water 1 week before carcinogen injections commenced and for the duration of the experiment. Primary tumors were detected by serial laparotomy under ether anesthesia performed at 2-month intervals and commencing after carcinogen injections had been completed. The average time to tumor onset was significantly delayed in rats receiving NMF and MSM (P = 0.0141 and 0.0398 respectively, Mantel-Haenszel test). In addition, fewer poorly differentiated tumors were noted in treatment groups. No weight loss or toxicity was observed. These findings demonstrate that the polar solvents significantly reduce the latent period to tumor onset in DMH-induced colon cancer and indicate the need to further investigate such compounds as chemopreventive agents.

1,2-Dimethylhydrazine↗
PubMed1988

Nonanatomic hepatic resection for secondary hepatic tumors with special reference to hemostatic technique.

The techniques for resection of hepatic tumors have traditionally been based on lobar anatomy. The morbidity and mortality associated with hepatic resection have been most closely correlated with intraoperative blood loss. The results of 37 hepatic resections for secondary neoplasms were retrospectively reviewed. This group included 18 patients who underwent anatomic resections and 19 patients who underwent nonanatomic resections. The nonanatomic group experienced significantly less blood loss, shorter operating times, shorter hospital stays, and no significant difference in long-term survival. A positive relationship between blood loss and postoperative complications is demonstrated for the combined groups. These results support the use of nonanatomic resection whenever feasible for secondary hepatic tumors. We describe the technique for nonanatomic hepatic resection for metastatic lesions, with special emphasis on hemostatic techniques.

Adult↗
PubMed1988

Synergistic cytotoxicity between dimethyl sulfoxide and antineoplastic agents against ovarian cancer in vitro.

Dimethyl sulfoxide is a well-known differentiating agent that has been shown to inhibit tumor growth in vitro. We hypothesized that antineoplastic agents might show synergistic cytotoxicity when combined with 10% dimethyl sulfoxide. Twenty-four malignant ovarian tumors were removed and used in tests to determine the cytotoxicities of 10% dimethyl sulfoxide alone, each of six antineoplastic agents alone, and 10% dimethyl sulfoxide plus each antineoplastic agent. Cytotoxicity results for 10% dimethyl sulfoxide alone and each antineoplastic agent alone were used to evaluate each combination of dimethyl sulfoxide and an antineoplastic agent for synergy. There were 14 synergistic responses that were statistically significant at the p less than 0.01 confidence level between 10% dimethyl sulfoxide and an antineoplastic agent against the ovarian tumors. Seven of these responses were significant at the p less than 0.0003 level. This is strong evidence that true synergistic cytotoxicity occurs when an antineoplastic agent is combined with 10% dimethyl sulfoxide. We conclude that intraperitoneal delivery of antineoplastic agents in 10% dimethyl sulfoxide may be useful in the treatment of certain ovarian cancers.

Anthraquinones↗
PubMed1988

Cytotoxicity of dimethyl sulfoxide and antineoplastic combinations against human tumors.

Five human tumor reference cell lines were tested in vitro against 0 percent, 5 percent, and 10 percent DMSO; four antineoplastic agents; and combinations of 5 percent or 10 percent DMSO plus each antineoplastic agent. Synergistic cytotoxicity between DMSO and antineoplastic agents against each cell line were demonstrated. We have concluded that delivery of standard doses of antineoplastic agents in 5 percent or 10 percent DMSO may be useful in the treatment of some tumors because of the marked increase in tumoricidal effect seen with some DMSO and drug combinations. Alternatively, lower doses of antineoplastic agents might be delivered in DMSO, producing the same cytotoxic effect as a full dose of drug without DMSO but with less systemic toxicity.

Antineoplastic Agents↗
PubMed1988

Suppression of primary and secondary peptides with somatostatin analog in the therapy of functional endocrine tumors.

Sandostatin (SMS 201-995 (SMS)), a potent, long acting analog of native somatostatin was used in five patients with functional endocrine tumors (gastrinoma, two patients; insulinoma, one patient; glucagonoma, one, and adult onset nesidioblastosis, one). Primary and secondary peptide levels were obtained during provocation with a test meal, a calcium infusion, a secretin bolus and either a glucagon or tolbutamide bolus. During provocation test, the levels of the primary peptides insulin and C-peptide (nesidioblastosis and insulinoma), gastrin (gastrinoma), glucagon (glucagonoma) and the secondary peptides calcitonin, gastrointestinal peptide, gastrin releasing peptide, motilin, neurotensin, pancreatic polypeptide, somatostatin, substance-P and vasoactive intestinal peptide were obtained at predetermined intervals and quantitated by radioimmunoassay. SMS therapy was begun and peptide levels were again obtained during provocation. SMS suppressed basal primary peptide levels in all patients by more than 50 per cent. In 23 of 26 provocative tests, SMS effectively decreased circulating peptide levels by more than 50 per cent. Thirteen instances of elevated basal secondary peptides were discovered, and SMS universally suppressed these levels by a mean of 54 per cent. Of the 44 provocative tests performed, elevated secondary peptide levels were present in 41. SMS was effective in 31 of these 41 tests. The mean suppression of these provoked secondary peptide levels was 70 per cent. SMS effectively suppresses both basal and provoked peptides and, thus, provides relief of the clinical symptoms induced by pathologic elevations of primary and secondary peptides.

Adenoma, Islet Cell↗