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Biomedical subjects

E A Woltering

Publications and source records attributed to E A Woltering.

At least 37 records · Page 2Linked to original sources
PubMed1997

Intravitreal injection of octreotide acetate.

This study was conducted to determine the feasibility of injecting the somatostatin analogue, octreotide acetate (OA), into the vitreous cavity. Previous work suggests that octreotide effectively inhibits angiogenesis in vitro, thus its use in vivo may slow the progression of proliferative eye disease. Fifty micrograms of aqueous OA in 50 microliters aqueous solution was injected into the mid-vitreous of kitten eyes (n = 6), and OA levels were monitored over 4 days. A long-acting release form of octreotide (OA-LAR) was also injected into the mid-vitreous of rabbit eyes at doses of 0.36 (n = 16), 1.1 (n = 1), 2.1 (n = 1), 4.05 (n = 1), 8.2 (n = 1), and 36 mg (n = 3) in solution; and octreotide concentrations were measured at various time points over 42 days. OA concentrations were determined by a highly specific radioimmunoassay. Aqueous octreotide was eliminated rapidly (t1/2 = 16 hours) from the vitreous of the kitten eye, with only negligible amounts recoverable 4 days post-injection. In the long-acting form, OA in the rabbit eye reached peak levels at 28 days. By 42 days, OA levels had declined to the 14-day level. Doses of OA-LAR of 1.1 mg or less produced no gross evidence of clinical toxicity and elicited no grossly visible ocular side effects. Doses greater than 1.1 mg produced significant toxicity, including cataracts and rubeosis. The 28-day peak release for long-acting OA implies that monthly intravitreal injections could provide continual high levels of OA. Intravitreal injection of long-acting OA provides sustained, high concentrations of drug, and deserves further study as a potential treatment of proliferative eye diseases.

Animals↗
PubMed1997

Retinal toxicity of intravitreous octreotide in the rabbit.

OBJECTIVE: To evaluate the ocular toxicity of intravitreous octreotide. DESIGN: New Zealand white rabbits weighing approximately 2 kg were given 5 mg (group 1, two eyes), 2 mg (group 2, four eyes), 1 mg (group 3, four eyes), 0.5 mg (group 4, two eyes), 0.3 mg (group 5, two eyes) or 0.1 mg (group 7, two eyes) of octreotide acetate, two doses of 0.3 mg 1 week apart (group 6, four eyes) or 0.1 mL of balanced salt solution (group 8 [control group], two eyes). OUTCOME MEASURES: Findings on clinical examination and electroretinography, performed before and 10 days after injection, and on light microscopy. RESULTS: Cataracts developed in groups 1 and 2. No clinical changes were found in groups 3 to 8. Electroretinography showed various degrees of decrease in the b-wave amplitude in groups 1 and 2; the results were normal in groups 3 to 8. Histologic examination showed macrophage and monocyte infiltration in the vitreous and retina in group 1. No histologic change was seen in the eyes in groups 2 to 8. CONCLUSIONS: Octreotide injected intravitreally is safe at dosages of 1 mg or less.

Animals↗
PubMed1996

Improved outcome of surgical flaps treated with topical dimethylsulfoxide.

OBJECTIVE: The objective of this study was to analyze the effect of dimethylsulfoxide (DMSO) on skin flap viability. BACKGROUND: Dimethylsulfoxide has been shown to decrease necrosis of random skin flaps in the rat model, but no human studies have been performed. The authors performed a randomized, prospective study on the effect of DMSO on skin flap viability in patients undergoing mastectomy and inguinal lymphadenectomy. METHODS: Twenty-four patients had topical 60% DMSO applied to their flaps every 4 hours x 10 days after operation and 27 patients had operation alone. The maximum area of flap ischemia was traced by a masked observer and measured by cut and weigh technique. Significance of differences between the treatment and control group was determined by Student's test. RESULTS: The mean area of ischemia for the DMSO group was 16.33 U versus 44.93 U for the control group. This difference was statistically significant (p = 0.01). CONCLUSIONS: The authors conclude that topical application of DMSO reduces skin flap ischemia in humans and recommend its use after operation in which skin flaps are created.

Administration, Topical↗
PubMed1996

Calcium reverses octreotide inhibition of insulin and glucagon levels in patients with insulinoma and glucagonoma.

Excessive secretion of peptides causes the clinical syndromes associated with functional gastro-intestinal tumours. The somatostatin analogue octreotide acetate inhibits peptide release from a variety of tumours. This study investigated the interactions of calcium and somatostatin analogues on peptide release in two patients, one with a glucagonoma (patient A) and one with an insulinoma (patient B). Peptide responses were evaluated before (fasting levels) and after provocative tests (a 4-hour calcium infusion, an intravenous tolbutamide infusion, a secretin bolus and a standard test meal) in the absence and presence of octreotide acetate treatment (100 micrograms subcutaneously every 8 h). Patients A and B had elevated fasting plasma levels of glucagon and insulin, respectively, which were reduced by octreotide therapy by 73 and 50%, respectively. The peak provoked levels and calculated values for peptide synthesis were lower after octreotide therapy. In both patients, tolbutamide provoked most peptide release, and calcium infusion was the least susceptible to the effects of octreotide therapy. Calcium appears to inhibit octreotide suppression of glucagon and insulin secretion in patients with glucagonoma and insulinoma, respectively. Calcium may stimulate peptide release from endocrine tumours by suppressing the inhibitory effects of endogenous somatostatin. Normalisation of serum calcium, either surgically or pharmacologically, may improve the effectiveness of somatostatin analogue therapy.

Antineoplastic Agents, Hormonal↗
PubMed1996

Effect of a somatostatin analog (octreotide acetate) on the growth of retinal pigment epithelial cells in culture.

PURPOSE: Proliferative vitreoretinopathy is a serious complication of retinal detachment surgery in which retinal pigment epithelial cells abnormally proliferate within the vitreous cavity and under the retinal surface. Octreotide acetate, a somatostatin analog, has been shown to inhibit the cellular proliferation of a variety of cell types. The aim of this study was to investigate the effect of octreotide acetate on the growth of rabbit retinal pigment epithelial cells in culture. METHODS: Retinal pigment epithelial cells were isolated from rabbits and maintained in culture. Cells were exposed to standard media or media supplemented with octreotide acetate 10(-4) M to 10(-12) M for five days. Each concentration of octreotide acetate was tested in quadruplicate. RESULTS: Exposure of rabbit retinal pigment epithelial cells to octreotide acetate significantly inhibited proliferation with a peak effect at 10(-8) M. The effect of octreotide is biphasic with higher and lower concentrations having less effect than 10(-8) M. CONCLUSIONS: This study suggests that octreotide acetate may be useful in the treatment of proliferative vitreoretinopathy; however, the optimum therapeutic dose range for this drug may be narrow.

Animals↗
PubMed1995

Consensus statement: octreotide dose titration in secretory diarrhea. Diarrhea Management Consensus Development Panel.

Octreotide is an effective therapeutic option in controlling secretory diarrhea of varied etiology. However, marked patient-to-patient differences in the antidiarrheal effects necessitate titration of octreotide dose in individual patients to achieve optimal symptom control. A consensus development panel established guidelines for octreotide dose titration in patients with secretory diarrhea. Overall, the panel recommended an aggressive approach in selecting the initial octreotide dose and in making subsequent dose escalations in patients with secretory diarrhea due to gastrointestinal tumors (eg, carcinoids, VIPomas), AIDS, dumping syndrome, short bowel syndrome, radiotherapy, or chemotherapy. To avoid hypoglycemia in patients with diabetes mellitus-associated secretory diarrhea, the panel recommended a low initial octreotide dose and a conservative titration regimen with close monitoring a blood glucose levels. The end point of therapy should focus on a reduction in diarrhea (frequency of bowel movements or stool volume) rather than normalization of hormonal profile. Overall, octreotide is well tolerated; principal side effects are transient injection site pain and gastrointestinal discomfort. For many patients with secretory diarrhea, octreotide therapy is expected to improve the overall health and quality of life and in the long run will lessen health care costs.

Carcinoid Tumor↗
PubMed1995

Treatment of metastatic carcinoid tumors using multimodality therapy of octreotide acetate, intra-arterial chemotherapy, and hepatic arterial chemoembolization.

BACKGROUND: Overall survival and quality of life in patients with metastatic carcinoid tumors depend on control of tumor growth and suppression of amine-induced symptoms. METHODS: We report on a series of 10 patients with carcinoid tumors metastatic to the liver who were treated with long-term octreotide acetate therapy (100 to 500 micrograms three times a day), sequential intra-arterial 5-fluorouracil (5-FU) infusions, and hepatic tumor chemoembolization. RESULTS: All 10 patients remained asymptomatic or had extremely mild symptoms after combined modality therapy (mean follow-up duration of 51.5 months). Sixty percent of the patients had a > 50% reduction of their tumor size (mean duration 42 months). An additional 30% experienced stabilization of tumor growth for 6 months or longer. Five of the 10 patients are currently alive. The mean group survival is 58 months since diagnosis (range 33 to 115) and 40 months since starting therapy (range 12 to 65). CONCLUSIONS: Combining octreotide acetate, intra-arterial 5-FU, and tumor chemoembolization effectively retards tumor growth while providing excellent symptom control.

Aged↗
PubMed1994

Pharmacokinetics and results of dose escalation in cis-platin hyperthermic isolation limb perfusion.

BACKGROUND: We analyzed prospectively collected data on 145 cis-platin hyperthermic isolation limb perfusion (HILPs) for melanoma and soft-tissue sarcoma to determine the pharmacokinetics and maximum tolerable dose of cis-platin. There were 70 melanoma and 75 sarcoma patients. Dosages ranged from 26 to 265 mg/m2. Perfusate and systemic cis-platin levels were measured in patients perfused at doses of 190-200 mg/m2. Tissue levels were measured in patients perfused at 123-209 mg/m2. METHODS: Cis-platin HILP was well tolerated up to doses of 250 mg/m2 for lower extremities. Higher doses produced toxicities of rhabdomyolysis, myoglobinuria, hyponatremia, and neuropathy. Systemic levels of cis-platin were equivalent to those of routine intravenous administration, while perfusate levels were 33 times higher. Tissue levels of cis-platin were five to six times higher than effective intravenous levels. RESULTS: Six melanoma patients have developed local recurrences. All were perfused at doses < 120 mg/m2. However, regional nodal recurrences have occurred in six other patients perfused at doses < or = 200 mg/m2. Four sarcomas have recurred locally, but three of them were present at the time of perfusion. CONCLUSIONS: We conclude that 250 mg/m2 is the maximum tolerable dose of cis-platin for lower-extremity HILPs. Neoadjuvant cis-platin HILP may improve local control rates for sarcomas. However, no tolerable dose of cis-platin provides control of nodal metastases from melanoma.

Adult↗
PubMed1994

Protective effect of doxorubicin in vitamin C or dimethyl sulfoxide against skin ulceration in the pig.

BACKGROUND: Accidental extravasation of doxorubicin leads to skin necrosis and significant morbidity. Based on our previous work in the rat, we hypothesized that the free radical scavengers dimethyl sulfoxide (DMSO) and vitamin C prevent doxorubicin-induced skin ulcers in white swine. METHODS: Fifteen white swine were anesthetized and injected with 0.5 mg of doxorubicin (1 mg/ml) intradermally delivered in saline, 10% DMSO, 20% DMSO, vitamin C (1 mg/ml), or vitamin C in 20% DMSO. Presence of skin ulceration and ulcer size, in the two greatest dimensions, was determined weekly for 3 weeks. RESULTS: Delivery of doxorubicin in DMSO and/or vitamin C lowered the ulcer incidence from 87% to 27% (p < 0.0001) when compared with delivery in saline. CONCLUSION: We conclude that the free radical scavengers DMSO and vitamin C are capable of lowering the incidence of doxorubicin-induced skin ulcers and could significantly lessen the morbidity associated with doxorubicin extravasation.

Animals↗
PubMed1994

Octreotide does not alter endotoxin lethality in mice or endotoxin-induced suppression of human leukocyte migration.

Octreotide, a somatostatin analog, was evaluated for its effects on long-term survival in a mouse model of endotoxemia and for its effects on endotoxin-induced suppression of human leukocyte migration. Swiss Webster mice were simultaneously rendered endotoxemic with a single intraperitoneal injection of 800 micrograms E. coli Lipopolysaccharide (LPS) and treated with one of four doses of subcutaneous (s.c.) octreotide (1.0 mg/kg in 0.4 ml saline, 0.1 mg/kg in 0.4 ml saline, 0.1 mg/kg in 0.04 ml saline, or 0.001 mg/kg in 0.04 ml saline) or saline alone (fluid-resuscitated control group: 0.4 ml saline s.c.; or non-fluid-resuscitated control group: 0.04 ml saline s.c.). Octreotide was continued with or without supplemental s.c. fluid resuscitation (0.4 ml saline) at eight hour intervals for either twenty-four or forty hours. There was no statistical significance to differences in long-term survival between comparable groups of octreotide treated vs saline treated animals during the entire fourteen day period of observation. Fluid resuscitation during the first forty hours following endotoxemia induction delayed death, but did not significantly improve long-term survival. In vitro work was conducted to determine the effect of octreotide on endotoxin-induced suppression of human leukocyte migration. Octreotide at concentrations ranging from 3.05 x 10(-5) Molar to 3.05 x 10(-11) Molar had no significant effect on leukocyte migration. In this study octreotide treatment failed to improve long-term survival in mice with endotoxemia and did not alter endotoxin-induced suppression of leukocyte migration.

Animals↗
PubMed1994

Changes in serum sex steroid levels during megestrol acetate therapy.

We hypothesized that megestrol acetate (MA) may work on breast carcinoma by inducing changes in serum sex steroid levels. We prospectively measured levels of follicle-stimulating hormone (FSH), luteinizing hormone (LH), dehydroepiandrosterone (DHEA), estrone (E1), and estradiol (E2) in 18 postmenopausal women before and during megestrol acetate therapy. MA significantly suppressed serum FSH, LH, DHEA and E1 levels. However, this was accompanied by a marked increase in serum E2 levels as measured by radioimmunoassay performed on whole serum. MA did not cross-react with the anti-E2 antibodies used in the assay. Elevated E2 levels also occurred in oophorectomized and/or adrenalectomized patients indicating the ovary and adrenal are not the source of the elevated E2 levels. We conclude that MA may be metabolized to oestrogenic compounds that crossreact with antibodies to E2, explaining the elevated E2 levels observed. The effects of these oestrogenic metabolites on breast carcinoma are unknown.

Adrenalectomy↗
PubMed1994

Postreceptor signal transduction mechanisms involved in octreotide-induced inhibition of angiogenesis.

BACKGROUND: Somatostatin analogues inhibit peptide release and cell growth through multiple postreceptor signal transduction mechanisms (PRSTM), including G proteins (GP), cyclic adenosine monophosphate (cAMP), calcium, protein kinase C (PKC), and tyrosine phosphatase (TP). Octreotide acetate (OA), a somatostatin analogue, has been shown to inhibit angiogenesis; however, the PRSTM involved are unknown. METHODS: Fertilized chicken eggs were obtained and incubated. On day 3, embryos were removed and placed in plastic wrap hammocks. On day 7, disks containing OA, test substances that interfere with PRSTM, or combinations of OA plus a test substance were placed on the developing chorioallantoic membrane. Blood vessel growth under each disk was assessed at 24 hours. Data were evaluated by chi-squared analysis. RESULTS: OA's ability to inhibit angiogenesis is significantly diminished when combined with calcium, bradykinin (increases calcium), pertussis toxin (inhibits GP), or 3-isobutyl-1-methylxanthine (increases cAMP). In contrast, no significant decrease is noted in OA's ability to inhibit angiogenesis when combined with phorbol ester (activates PKC) or vanadate (inhibits TP). CONCLUSIONS: OA-induced inhibition of angiogenesis is GP, calcium, and cAMP dependent and is PKC and TP independent. Better understanding of the PRSTM involved with OA-induced inhibition of angiogenesis may lead to enhancement of OA's effect on angiogenesis.

Animals↗
PubMed1994

Detection of occult gastrinomas with iodine 125-labeled lanreotide and intraoperative gamma detection.

BACKGROUND: Surgical exploration for gastrinoma has a high failure rate because of small primary tumors and occult metastasis. Despite extensive preoperative and intraoperative tumor localization, only 30% to 40% of patients with gastrinoma are cured by surgery. Two patients with unlocalized gastrinomas were studied with intraoperative gamma detection of an iodine 125-labeled somatostatin analog, lanreotide, to localize their tumors. METHODS: Both patients were challenged before operation with 100 micrograms of octreotide acetate, and both had circulating gastrin levels suppressed by greater than 50%. Iodine 125-labeled lanreotide (100 to 150 muCi) was injected during exploration, and an intraoperative gamma detector was used to detect tumor binding of the analog. RESULTS: In patient 1 a single source of increased counts was discovered in a retroduodenal lymph node, which was excised; no other tissue was removed. Histologic study of this node failed to demonstrate tumor; however, the patient's gastrin level was normal (63 pg/ml) 4 months after operation. In patient 2 five areas of increased counts were discovered and excised. Three of these five areas had visible tumor on microscopic examination. Three months after operation the patient's fasting gastrin level was 103 pg/ml. CONCLUSIONS: Intraoperative gamma detection of radiolabeled peptides may allow the localization of occult tumors that contain specific peptide receptors.

Adult↗
PubMed1994

An improved method of needle localized biopsy of nonpalpable lesions of the breast.

We have created a modified technique of localization biopsy of the breast that more easily identifies the position of the wire tip after placement and before biopsy. After wire placement, metallic skin markers are placed on the nipple and wire entry site. The patient is then positioned on a roentgenography table in the same position to be used during biopsy. A supine roentgenogram of the breast is obtained. At the time of the biopsy, this roentgenogram is aligned with the corresponding markers on the skin of the patient and the position of the wire tip is noted. A curvilinear incision along Langer's lines can then be made at that site. This procedure was used in 53 consecutive biopsies of nonpalpable mammary lesions. In all instances, the biopsy incisions were independent of the wire insertion sites and in each instance, the lesion was excised in a single specimen. Compared with other techniques, our method is simple, inexpensive, requires no special equipment and results in only a minimal increase in radiation dose to the breast (50 millirad). The decrease in the amount of tissue dissection without decreasing accuracy afforded by our technique can improve compliance with the American Cancer Society's recommended surgical guidelines for breast preservation therapy.

Biopsy, Needle↗
PubMed1993

Inhibition of angiogenesis by somatostatin and somatostatin-like compounds is structurally dependent.

We have previously demonstrated that somatostatin analogues SMS 201-995 and RC-160 inhibit angiogenesis using the chorioallantoic membrane (CAM) of the developing chicken embryo. In this study, we evaluated the ability of native somatostatin 14 and nine somatostatin analogues to inhibit angiogenesis. Two-millimeter methylcellulose disks containing 50 micrograms of somatostatin or somatostatin analogue were implanted on the CAM of 6- to 7-day-old shell-less chick embryos. Inhibition of blood vessel growth was visually assessed and graded in the region of the disk 24-36 hr following implementation. The analogues SMS 201-995 and RC-160 showed statistically significant inhibition of neovascularization when compared to native somatostatin 14. The amino acid homology comparison of the nine analogues revealed that individual differences in their abilities to inhibit angiogenesis may be structurally dependent.

Animals↗
PubMed1993

Comparison of adrenal and extraadrenal pheochromocytomas.

BACKGROUND: It is commonly believed that extraadrenal tumors (EAT) of the paraganglion system are more likely to be malignant than adrenal tumors (AT) and carry a poorer prognosis. We analyzed 73 paraganglion tumors (PT) to determine whether EATs are more likely to be malignant or have a poorer prognosis than ATs. METHODS: A review of patients with PTs at three institutions was performed. Malignant tumors were defined as those that metastasized. Comparison of the frequencies of malignant tumors was performed by chi-squared analysis. Survival distributions were determined by Kaplan and Meier analysis. Comparison of survival distributions was performed by log-rank analysis. RESULTS: There were 73 patients. There were 51 ATs, of which 24 were malignant, and 22 EATs, of which 11 were malignant (p = 0.82). The 5-year survival rate was 77% for patients with ATs and 82% for patients with EATs (p = 0.29). The 5-year survival rate for patients with malignant ATs was 57%, and 74% for patients with malignant EATs (p = 0.15). There were no significant differences in disease-free survival rates on the basis of tumor site. CONCLUSIONS: We were unable to demonstrate that EATs are significantly more likely to be malignant than ATs. The survival and disease-free survival rates for malignant ATs and EATs are similar, and among malignant tumors, there may be no prognostic value of the anatomic location.

Adolescent↗
PubMed1992

Long-term efficacy of octreotide in the treatment of Zollinger-Ellison syndrome.

Nine patients with Zollinger-Ellison syndrome were treated with octreotide acetate (100 micrograms delivered subcutaneously three times daily) and followed up for 1 to 48 months. Serum gastrin levels were obtained at predetermined intervals. All patients had elevated baseline fasting gastrin levels (greater than 150 ng/L [greater than 150 pg/mL]). One month after administration of octreotide, gastrin levels were in the reference range for five (62%) of eight patients, and a mean gastrin suppression rate of 76% was achieved (ie, values were a mean of 76% less than baseline values). One year after administration of octreotide, five (71%) of seven evaluable patients had gastrin levels of less than 200 ng/L (200 pg/mL), and the mean gastrin suppression rate was more than 80% for these seven patients. During the second year, control at these levels was maintained in four patients; one patient continued to have controlled levels for 42 months. Complete symptomatic response occurred in seven patients (78%), and partial response in two patients (22%). All six patients with diarrhea before treatment were cured of it. Octreotide acetate provides efficacious long-term suppression of elevated gastrin levels and excellent symptomatic relief in patients with Zollinger-Ellison syndrome.

Abdominal Pain↗