PubMed HealthSearch

Biomedical subjects

A B Cruz

Publications and source records attributed to A B Cruz.

At least 19 recordsLinked to original sources

Effect of compounds from Mandevilla velutina on bradykinin-mediated contractile and relaxant responses of the isolated guinea pig trachea.

This study examines the action of three putative functional bradykinin (BK) antagonists isolated from Mandevilla velutina on BK and other agonist-induced contraction or relaxation responses in intact or in epithelium-denuded strips of tracheal muscle from guinea pigs. Compound MV 8612 (8 and 16 microM) and MV 8610 (12 and 24 microM) caused a graded rightward displacement of BK dose-response curves in the isolated guinea pig trachea (dose ratio 2- to 4-fold). Compound MV 8608 (28 microM) had a small effect on BK contractile responses. At high concentrations, compound MV 8612 (24 microM) caused a slight but significant depression of the BK-induced maximal responses. These pharmacological actions appear to be quite selective towards BK, since within the same concentration range these compounds failed to interfere with the sensitivities to prostaglandin F2 alpha, carbachol and histamine. However, these compounds significantly enhanced maximal responses to the latter two agonists, an action that was not influenced by indomethacin. In addition, MV 8612 and MV 8608 (16 and 56 microM) significantly potentiated BK-mediated epithelium-dependent relaxation responses in preparations precontracted with carbachol. These compounds also significantly potentiated isoprenaline but not theophylline-relaxant responses, an action that seems to occur independently of the generation of cyclooxygenase products of arachidonic acid pathway. These results further extend our previous studies and indicate that some of the M. velutina compounds exert a weak though selective antagonistic action against BK-induced contractile responses of the isolated epithelium-denuded guinea pig tracheal smooth muscle and potentiate BK-induced relaxations in tissues with intact epithelium precontracted with carbachol.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals

Prostaglandin E1 enhances tumoricidal activity of 5-fluoro-2'-deoxyuridine in rats.

Addition of prostaglandin E1 (PGE1) to 5-fluoro-2'-deoxyuridine (FUDR) infused via the portal vein has been shown to diminish both the regional and the systemic toxicity of this chemotherapeutic agent. The effect of concomitant PGE1 infusion on tumor growth has not yet been determined. This study was designed to assess the effect of PGE1 in combination with FUDR on an established adenocarcinoma in the rat model. Fifty-gram Fischer rats underwent placement of a 3-mm3 fragment of colon carcinoma 4047 in the left thigh pad. After 6 weeks to allow for tumor growth, the animals were randomly assigned to receive a 7-day intravenous infusion of (1) saline, (2) PGE1 (0.1 microgram/kg/min), (3) FUDR (3 mg/kg/day), or (4) PGE1 + FUDR. At 10 days animals receiving PGE1 + FUDR had a significant decrease in tumor volume (mm3, log 10) (3.39 +/- 0.24 vs 3.85 +/- 0.12, P less than 0.05) compared with animals receiving FUDR alone. We conclude that PGE1 may be useful as an adjunctive cytotoxic agent.

Adenocarcinoma

Extract and compounds obtained from Mandevilla velutina inhibit arachidonic acid-induced ear oedema in mice, but not rat stomach contraction.

This study was designed to analyse the effect of crude extract (CE) and some pure compounds isolated from M. velutina on arachidonic acid (AA)-induced ear oedema in mice. The effect of these compounds on contractions in the rat stomach induced by AA and prostaglandin E2 (PGE2) was also investigated. The CE given orally to mice (50-400 mg/kg) 1h before inhibited the ear oedema in a dose-dependent manner, with a maximal inhibition (MI) of 56%. Given topically, compound MV8612 (200-600 mg/ear) isolated from this plant inhibited the oedema in a concentration-dependent manner with a MI of 66%, while compounds MV8608 and MV8610 (100-600 mg/ear) caused less inhibition, MI 29% and 39% respectively. Compound MV8612, given i.p. (3-30 mg/kg) 30 min before, also caused a dose-dependent inhibition of AA-induced ear oedema (MI of 60.5% compared with 28% and 49% for MV8608 and MV8610). Indomethacin (0.25-1.0 mg/ear) applied topically had no effect, but orally (1-10 mg/kg) gave MI of 66%. Phenidone given orally (10-100 mg/kg) gave a MI of 30% but it was very potent topically (0.5-2 mg/ear) (MI 66%). Nordihydroguaiaretic acid applied either topically (0.5-2.0 mg/ear) or orally (10-100 mg/kg) caused MI of 63% and 47%, respectively. BW 755C, orally (10-100 mg/kg), inhibited the AA-induced oedema in a dose-dependent manner (MI 48%), but was less effective when applied topically (0.25-1 mg/ear) (MI 32%). In the rat stomach preparation, compounds MV8608 and MV8612 (0.1-20 micrograms/ml) had no significant effect on contractions to AA or PGE2, while indomethacin (0.01-3 micrograms/ml) potently inhibited AA contraction, but had no effect on the PGE2 response. These results indicate that MV8608 and MV8612 exhibit both a topical and a systemic anti-inflammatory profile, presumably by a mechanism not related to inhibition of cyclooxygenase.

4,5-Dihydro-1-(3-(trifluoromethyl)phenyl)-1H-pyraz

Immunocytochemical analysis of estrogen receptors in human breast carcinomas. Evaluation of 130 cases and review of the literature regarding concordance with biochemical assay and clinical relevance.

An estrogen receptor-immunocytochemical assay (ER-ICA) was performed on frozen sections of 130 samples of human breast carcinoma. A standard dextran-coated charcoal assay (DCCA) was performed on the same samples. Concordance of results between the tests was 91%. The sensitivity and specificity of the ER-ICA, compared with the DCCA, were 92% and 89%, respectively. We describe the ER-ICA technique and review the literature regarding the use of the ER-ICA in evaluating breast cancer with respect to the agreement of results with the DCCA, the nature of discordant results, the ability to predict the clinical response to hormone therapy, and the ability to predict disease-free survival. The combined experience of many studies has shown that the ER-ICA is a highly specific and sensitive method for measuring the level of ERs in breast tumors with a high level of agreement with the DCCA. Early experience has suggested that the ER-ICA can predict the response to hormone therapy and disease-free survival, as well as or better than the DCCA. The evaluation of receptor heterogeneity, made possible by the ER-ICA, may enhance our ability to discriminate ER-positive tumors with a relatively high risk of recurrence.

Breast Neoplasms

Carcinoma of the pancreas: a retrospective review.

Eighty-five patients with adenocarcinoma of the pancreas were reviewed in order to evaluate the efficacy of our methods of diagnosis and treatment. The most useful diagnostic test was percutaneous transhepatic cholangiography (PTC) with a diagnostic rate of 96%. Pancreaticoduodenectomy (Whipple procedure) and total pancreatic resection were performed in 13 and 2 patients, respectively. The remaining 50 patients underwent various palliative drainage procedures. Twenty patients did not undergo operation for various reasons. The primary tumor was found in the head of the pancreas in 50 patients (59%), the body in 6 patients (7%), and in the tail in 8 patients (9%). Postoperative complications, including sepsis, bleeding, intra-abdominal abscesses, and anastomotic leaks, occurred in 37% of the patients. There were one operative and 9 postoperative deaths. The average survival for those patients undergoing surgical intervention was 6 months. There were no 5-year survivors.

Adult

Portal infusion of tumor necrosis factor increases mortality in rats.

Tumor necrosis factor (TNF) is a protein found in the serum of mice presensitized with BCG following injection of endotoxin. Although TNF has been shown to cause hemorrhagic necrosis of certain tumors, the marked toxicity of recombinant human TNF has limited the clinical usefulness of this compound. This experiment was designed to determine whether hepatic metabolism would reduce the systemic toxicity of TNF delivered by the portal circulation. Twenty male Fischer rats received a continuous infusion of recombinant human TNF (100 micrograms/kg/day), 10 through a portal venous branch, and 10 through a branch of the inferior vena cava. Control animals received an infusion of carrier solution by the same route. After 7 days the animals were sacrificed and their organs weighed and sectioned. Mortality in the portal TNF group was 100%. The animals followed the clinical pattern seen with lethal TNF injection. Histologic sections revealed significant gastric and small intestinal mucosal injury, pulmonary edema, and acute tubular necrosis. Animals receiving TNF systemically lost more weight per day of infusion than controls, but followed a relatively benign course. Systemically infused animals had evidence of mild pulmonary edema, and a periportal mononuclear infiltrate in the liver, but no obvious renal or gastrointestinal injury. In a second experiment the effect of escalating doses of portal TNF infusion on liver enzymes was assessed. TNF was infused intraportally at 10, 50, or 100 micrograms/kg/day for 3 days. Control animals received a carrier solution. Mortality was dose-related with 100% mortality in animals receiving 100 micrograms/kg/day, and 40% mortality in the 50 micrograms/kg/day group.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals

Demonstration of anti-bradykinin compounds in callus cultures of Mandevilla velutina.

Calluses from stems and leaves of Mandevilla velutina were grown in culture for 30, 45 and 60 days. Thin-layer chromatography of ethyl acetate extracts of calluses from stems of M. velutina revealed the presence of 6 compounds. Two of them had RF values identical to those of the anti-bradykinin (BK) compounds MV8609 and MV8610 previously isolated from the natural plant. The ethyl acetate extract (20 to 80 micrograms/ml) from stem callus culture antagonized in a concentration-dependent and reversible manner contractions caused by BK (0.1-1000 nM) in the isolated rat uterus. The extracts obtained from calluses cultured for 30, 45 and 60 days were about 79-, 63- and 31-fold more potent, respectively, in antagonizing BK than the crude extract obtained from the rhizome of the plant.

Animals

Needle aspiration biopsy of palpable breast masses.

One hundred fifteen patients underwent needle aspiration biopsy of palpable breast masses prior to open biopsy. Aspirates were obtained by surgical residents, prepared by a cytotechnologist present at the procedure, and evaluated by a single pathologist. Cytologic findings were interpreted as positive or highly suspicious for malignancy, normal or benign, or insufficient. All patients underwent open biopsy. Patients with positive or highly suspicious cytologic findings who preferred partial mastectomy and radiotherapy were offered a segmental mastectomy. No patient was offered total mastectomy based on cytologic findings alone. There were two false-positive and two false-negative results, for a 92 percent sensitivity and 97 percent specificity. The value of needle aspiration biopsy lies in its ability to identify patients at high risk for malignancy. Total mastectomy cannot be recommended based on cytologic findings alone. The setting of a surgical residency program does not adversely affect the reliability of the technique.

Adolescent

Adjuvant therapy in large bowel adenocarcinoma: long-term results of a Southwest Oncology Group Study.

The Southwest Oncology Group (SWOG) colorectal adjuvant study 7510 went through two phases. From 1975 to 1977, 309 patients were randomized to chemotherapy alone or the same chemotherapy plus immunotherapy. From 1977 until 1980, 317 patients were randomized among the same two therapy programs and a control group. With a minimum follow-up in either phase of greater than 7 years, data are now mature. They show no difference in relapse-free survival (RFS) nor overall survival (OS) in either the two-way phase or in the three-way phase. There is no indication, except possibly in one very small subset, that the addition of immunotherapy to chemotherapy provides an improvement in OS or in RFS. Using data from patients accrued after randomization to the control group, we fail to find evidence that either chemotherapy alone or chemoimmunotherapy improves OS or RFS when contrasted to outcomes obtained by patients on the control arm. In fact, we have significant evidence, at the P = .016 level, that chemotherapy does not improve OS by at least 50%; we also have significant evidence, at the P = .011 level, that chemoimmunotherapy will not improve OS by at least 25%. No evidence of efficacy was demonstrated for either treatment regimen, even though enough therapy was given to result in significant toxicities. Acute toxicity was at least moderate, but not fatal, in 75% of patients. Recognizable delayed toxicity included rare cases of fatal renal failure and acute leukemia.

Adenocarcinoma

Blockade of the bradykinin-evoked diphasic response of isolated rat duodenum by the crude extract of and compounds obtained from Mandevilla velutina.

The influence of an aqueous/ethanolic extract of M. velutina (CE) and of two compounds (MV 8608 and MV 8612) purified from the plant on BK-, Ad- and K+-induced responses of the rat duodenum was analyzed in vitro. In preparations precontracted with Ca2+, the CE (1 and 2 mg/ml) markedly inhibited BK-induced relaxation in a dose-dependent manner but was less effective against Ad-induced relaxation. The CE (0.5 mg/ml) also antagonized BK-induced relaxation and contraction of strips bathed in normal medium. The two compounds from M. velutina (10 and 20 micrograms/ml) also promoted a dose-dependent blockade of both responses to BK, only slightly depressing the response to K+.

Animals

Somatostatinoma: a case report and review of the literature.

Somatostatinomas are rare endocrine tumors that were first described in 1977. In addition to the present case report, there have been 31 cases reported in the literature. We have reviewed the literature to integrate the symptoms, physical findings, diagnostic tests, treatment, and length of survival of these patients. Although the symptoms that occurred in the majority of cases were those that are seen in most patients with intra-abdominal neoplasms, symptoms relating to the presence of excess circulating somatostatin--diabetes, maldigestion, and cholelithiasis--were frequently seen. Physical findings and the results of diagnostic tests were usually nonspecific. The majority of the patients underwent radical surgical procedures (Whipple procedure or pancreatic resection). The pancreas was the most frequent site of involvement (21/31 cases), but primaries in the duodenum, ampulla of Vater, cystic duct, and jejunum have been described as well. Metastases were most frequently seen in the liver and lymph nodes. Chemotherapeutic agents were administered to 10 patients, usually as adjuvant therapy, and appear to be useful in treating recurrent and metastatic disease. The one-year survival of these patients is 48%, which is better than that for patients with carcinoma of the pancreas or biliary tree. Therefore, it is important that the diagnosis of somatostinoma be made so that the patient may be treated accordingly and followed by serial somatostatin levels for evidence of metastasis or recurrent disease.

Adenoma, Islet Cell

Evaluation of nonpalpable breast lesions. Experience in a training institution.

Biopsy directed by needle localization is a safe and relatively simple method of obtaining abnormal tissue for histologic examination without sacrificing surrounding normal breast tissue. In the setting of a training institution, accurate results can be expected as technical skills are obtained by a variety of housestaff. In this series of 70 biopsies, the lesion targeted on mammography was removed on the initial attempt in all but 1 instance, for an overall accuracy of 99 percent.

Adenofibroma

Results of a 400-patient carcinoembryonic antigen second-look colorectal cancer study.

Four hundred patients with resectable colon and rectal cancers were operated on by 37 surgeons at 31 institutions. Patients were monitored with carcinoembryonic antigen (CEA) level determinations and clinical examinations. One hundred thirty patients had recurrences, and 75 were reoperated on, with 43 reoperations CEA-directed and 32 clinically directed. Two of 75 died within 1 month after the second operation. Twenty-two second-look patients remain free of disease 5 years after their second operation. The highest resectability of recurrent cancer occurred in patients with a CEA level below 11 ng/ml in whom the CEA level was determined at intervals of 1 to 2 months.

Adenocarcinoma

Upper gastrointestinal bleeding following renal transplantation.

Upper gastrointestinal bleeding has been shown to be a common complication of renal transplantation and one which carries a significant risk of mortality. In a retrospective review of 200 consecutive renal transplants in 194 patients, we found an incidence of only 6 per cent and a mortality rate of 8.3 per cent. Allograft survival in this group of patients was 58 per cent. These results are the product of careful preoperative evaluation, close attention to the patients for early signs of bleeding, and aggressive diagnostic and therapeutic intervention at the first evidence of bleeding. We also report an association of hypercalcemia with post-transplant upper gastrointestinal bleeding, with cessation of bleeding after parathyroidectomy.

Antacids

Combination chemotherapy for soft-tissue sarcomas: a phase III study.

A total of 144 patients with advanced sarcomas were entered into a randomized prospective protocol with four treatment arms utilizing different combinations of chemotherapeutic agents. Of these, 120 patients (83%) were judged acceptable. Treatment 1: actinomycin-D (Act-D), 0.01 mg/kg IV, days 1--5; phenylalanine mustard (L-PAM), 4 mg PO, days 1--10 every six weeks. Treatment 2: Act-D, 0.01 mg/kg IV, days 1--5; L-PAM, 4 mg PO, days 1--10; vincristine, 1 mg IV, days 1, 8, 15, 22, 29, 36, repeat every six weeks. Treatment 3: Act-D, 0.01 mg/kg IV, days 1--5; L-PAM, 4 mg PO, DAYS 1--10; NSC-1026, 200 mg/kg IV, days 1--6. Treatment 4: Adriamycin, 0.4 mg/kg IV, days 1, 2, 3, 8, 9, 10, then 2XWK starting day 15 (max. 1,200 mg). There was a provision that upon progression of the disease in the first three treatment regimens, patients would be crossed over to Treatment 4. Responses were as follows: 1 - Partial Response (PR) 1/25; No Change (NC) 9/25 (36%). gF2 - NC 17/26 (65%). 3 - NC 13/25 (52%). 4 - Complete Response (CR) 1/41; PR 6/41; (15%); NC 27/41 (66%). Clearly Treatment 4 was the best arm, with a 17% response rate and an initial progression rate of 17%. The only other response was a partial in 1. The difference is statistically significant (H = 17.247, P = 0.0006). If the responders to Adriamycin were analyzed without crossovers, the response rate would be 22% (6/27). (H = 14.079, P = 0.003). Median times to progression were 12.5, 8.7 weeks for 1 and 2, and 5 weeks for 3 and 4. There was no significant difference in the median survival times among the four treatment arms. It appears that Adriamycin as a single drug is superior to the drug combinations and would probably be even more effective used in combination with known active agents.

Antineoplastic Agents

Diagnosis and management of major tracheobronchial injuries.

From 1968 to 1978, 14 patients were treated for major tracheal or bronchial injury. Five injuries resulted from blunt trauma and nine from penetrating injury. Of the 5 patients with injury due to blunt trauma, three had avulsions of the right main bronchus from the trachea. In 2 of them, the injury was associated with stellate tears of the distal trachea and bronchus. The simple avulsion was repaired by a primary anastomosis of the right main bronchus to the distal trachea. For the other 2 patients, treatment consisted of right pneumonectomy. The remaining 2 patients in this group had complete transection of the trachea and underwent primary repair. Of the 9 patients with a penetrating injury, 4 had lacerations of the cervical trachea which were treated with neck exploration and tracheostomy. Three patients with partial transections of the cervical or upper mediastinal trachea were treated by primary closure. The other 2 patients had gunshot wounds to the distal right lateral trachea, which were treated by right thoracotomy and primary closure. There were no deaths, and the subsequent course was generally good in all patients.

Adolescent