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Biomedical subjects

M Merino

Publications and source records attributed to M Merino.

At least 55 records · Page 3Linked to original sources
PubMed1991

Biophysical absorption models for phenyl-alkyl acids in the absence and in the presence of surfactants. Studies in the rat small intestine.

The present study reviews and checks, by means of experimental work, some theoretical principles of a novel absorption-lipophilicity approach (Pl [symbol: see text] 160-Delfina et al., 1987), used to interpret the effects of synthetic surfactants on drug absorption. For this purpose the correlations between intestinal rat gut absorption constants and lipophilicity indexes are analyzed for a group of compounds belonging to a true homologous series (w-phenyl-alkyl carboxylic acids), in the absence and in the presence of polysorbate 80 in the luminal fluid. Evidence is given for the following surfactant actions: (a) at critical micelle concentration (CMC), the surfactant increases membrane polarity and simultaneously nullifies the limiting character of the stagnant aqueous layer adjacent to the membrane; (b) at supramicellar concentrations (SMC) the above actions become almost completely masked by the micellar solubilization of the compounds, which decreases their absorption rate constants. As a consequence of these interactions, correlation between membrane absorption and lipophilicity, which was clearly hyperbolic in free solution, becomes potential in the presence of surfactant at CMC, whereas at SMC a bilinear correlation is found. Pore absorption was much less affected. Mathematical and physiochemical reasons for this behaviour are outlined, and practical implications are briefly discussed.

Animals↗
PubMed1990

Preparative cytoreductive surgery in patients with metastatic renal cell carcinoma treated with adoptive immunotherapy with interleukin-2 or interleukin-2 plus lymphokine activated killer cells.

A total of 63 patients with metastatic renal cell carcinoma with the primary kidney tumor in place was accepted as candidates for immunotherapy at the Surgery Branch of the National Cancer Institute. Of the 63 patients 54 underwent nephrectomy and 9 were treated with the primary kidney tumor in place. Many of the patients underwent associated procedures, such as regional lymphadenectomy (11), venacavotomy with extraction of tumor thrombus (9), hepatic resection (2), pulmonary wedge resection (2), cholecystectomy (2), splenectomy (2), distal pancreatectomy (1), omentectomy (1) and contralateral adrenalectomy (1). Of the 54 patients 20 were not able to enter therapy because of tumor-related (17) or other medical (3) reasons that developed between the operation and therapy, while 34 were able to receive immunotherapy postoperatively. The 20 patients who were treated with either high dose interleukin-2 or interleukin-2 plus lymphokine activated killer cells soon postoperatively (mean 2.1 months) were able to tolerate roughly the same amount of interleukin-2 as the 74 who had undergone nephrectomy before referral to our institute and who were treated for a mean of 22 months after nephrectomy. Further studies, including a prospective, randomized trial, will be required to define the role of nephrectomy in patients with advanced renal cell carcinoma before treatment with interleukin-2 based immunotherapies.

Carcinoma, Renal Cell↗
PubMed1989

Absorption kinetics of beta-alanine as model compound in rat small intestine.

Contradictory results have been reported on intestinal beta-alanine absorption, although a generalized view is that it could be a passive, nonmediated process. Since previous data from our laboratory suggested that some competition arises between intestinal absorption of the gamma-amino acidic drug baclofen and beta-alanine, a rat jejunum in situ study was undertaken in order to gain insight into the mechanism of beta-alanine absorption. Perfusion solutions with initial beta-alanine concentrations ranging from 0.3 to 56 mM were used. The beta-alanine absorption was clearly identified as a saturable process which obeys Michaelis-Menten equation kinetics, as assessed through two computer-assisted procedures based on differential and integrated forms of this equation. Parameter values found were: Vm = 3.88-4.72 mg.ml-1.h-1 (43.6-52.9 mM.h-1), and Km = 0.97-1.13 mg.ml-1 (10.9-12.7 mM). Statistical analysis does not account for the existence of significant parallel passive diffusion pathways (less than 0.2 h-1).

Alanine↗
PubMed1989

Improved detection of allele loss in renal cell carcinomas after removal of leukocytes by immunologic selection.

We used immunologic selection to remove contaminating leukocytes from primary renal cell carcinomas and to improve detection of chromosome 3p allele loss. Leukocytes were removed from disaggregated renal cell carcinomas by a double-antibody, magnetic bead separation technique. Before immunologic selection, the preparations contained 26% +/- 15% (SD) tumor cells (n = 7); after immunologic selection, the preparations contained 76% +/- 12% tumor cells. The recovery of tumor cells in the purified preparations was about 10%. Detection of allele deletion was facilitated by immunologic selection. This method may be useful in allele deletion analysis of other human solid tumors that are contaminated with host leukocytes and, with appropriate modification, may be applied to tumors that are contaminated with other cell types.

Alleles↗
PubMed1988

Clear cell adenocarcinoma of the vagina and cervix: incidence, undetected disease, and diethylstilbestrol.

We conducted an incidence study to determine the occurrence rates of clear cell adenocarcinoma (CCAC) of the vagina and cervix in young women (born in 1940 and thereafter), and a case-series analysis, focusing on the maternal history of pregnancy and delivery and in-utero exposure to diethylstilbestrol (DES). Overall, 10 cases of CCAC had been listed in the files of the Connecticut State Tumor Registry prior to the study, and each of the 10 cases were confirmed as valid. In addition, another 10 cases, all previously undetected, were found after the tissue slides of young women listed as having other cancers of the vagina and cervix were reviewed by expert pathologists, suggesting that prior estimates of the incidence rate for CCAC must be misleading unless special efforts are taken to identify undetected cases. The incidence rates of vaginal CCAC (11 cases total) were highest in 1975-1979, and decreased slightly during 1980-1982. In the cervix (nine cases total), the rate increased consistently since 1970. History of in-utero exposure to diethylstilbestrol was obtained for five of eight vaginal cases and four of eight cervical cases of CCAC. In all nine cases, exposure to diethylstilbestrol was associated with a history of bleeding during the pregnancy or prior miscarriage. We conclude that the finding of stable (or rising) incidence rates for CCAC occurring nearly 30 years after the marked decrease in diethylstilbestrol sales emphasizes the need for continued clinical and epidemiologic studies of the etiology and clinical course of CCAC.

Abortion, Spontaneous↗
PubMed1987

Prognostic factors and sites of failure in FIGO Stage I, Grade 3 endometrial carcinoma.

The results of therapy and patterns of failure were analyzed for 60 patients with Stage I, Grade 3 endometrial cancer seen at Yale-New Haven Hospital between 1960 and 1980. Fifty-eight patients were treated with a combination of surgery and radiation; one was treated with surgery only; and one received radiation only. The overall absolute 5-year survival rate was 72.9% with poorer prognosis noted for patients greater than 65 years of age, older at time of their menopause, and with Stage IA disease. Of the 14 patients who recurred, distant sites were involved in 93% (13/14), with the lung the most common site of distant failure (5/14), followed by the upper abdomen (4/14). Pelvic sites were involved in 43% (6/14) of the treatment failures. The use of pelvic external beam radiation resulted in a reduction in pelvic recurrences, but did not improve overall survival. The predominance of distant failures despite pelvic radiation suggests the possibility of early vascular and transcoelomic spread in Stage I, Grade 3 endometrial adenocarcinomas. Thorough exploration of the upper abdomen, paraaortic nodes, and the obtaining of pelvic washings for cytology at the time of initial surgery, are recommended in addition to chest CT scans to help identify those patients with occult metastases. Prospective randomized trials in Stage I, Grade 3 patients employing adjuvant cytotoxic chemotherapy, hormonal therapy, and/or whole abdominal-pelvic radiation, should be considered in an attempt to improve survival in high-risk patients.

Carcinoma↗
PubMed1987

Uterine papillary serous carcinoma.

Reviewed are 37 patients with the diagnosis of uterine papillary serous carcinoma. Clinically, 19 patients presented as stage I, 9 as stage II, 1 as stage III, and 8 as stage IV. Four of 18 patients with clinical stage I disease who underwent surgery had pelvic metastases and five had disease spread beyond the pelvis. Three of nine clinical stage II patients had intraabdominal metastases. At least 50% myometrial invasion was found in 43% of the 30 hysterectomy specimens, and lymphatic invasion in the myometrium was demonstrated in 78% of the specimens. Each of the 15 patients with surgical stage I or II disease received local radiation therapy: 10 are alive and of these 9 are disease-free. Each of nine clinical stage II patients received intense radiation therapy and hysterectomy; seven are alive and of these four are disease free. The five-year survival for combined surgical stages I and II patients was 45%. The three-year survival for combined surgical stages III and IV was 11%. Thirteen patients have been treated with combination chemotherapy, 11 with cis-platinum-based combinations. Nine of these patients are dead; four are alive, with three of these having progressive disease.

Aged↗
PubMed1986

A clinical and histopathologic analysis of the results of conservation surgery and radiation therapy in stage I and II breast carcinoma.

One hundred eighty women with clinical Stage I or II operable breast carcinoma were treated by radiotherapy following local tumor excision at Yale-New Haven Hospital through 1980. With a median follow-up time of 6.9 years, the actuarial 5-year overall and disease-free survival rates were 82% and 78%, respectively. The 5-year actuarial breast-recurrence-free survival rate was 92%. Several clinical-histopathologic features and treatment parameters were assessed for their significance as predictors of local breast failure or distant relapse. Cox lifetable regression analysis showed that patients with clinical Stage II carcinomas had significantly worse overall and relapse-free survival rates, but clinical stage alone had no effect on the rate of breast recurrence. Furthermore, a decrease in overall and disease-free survival was evident when necrosis was present in the tumor or when patients had an infiltrating lobular carcinoma. Breast recurrence-free survival was also influenced adversely by the presence of these two tumor features, especially when either tumor necrosis or infiltrating lobular carcinoma was found in conjunction with clinical Stage II lesions. Other histologic features such as grade, vascular invasion, perineural invasion, or the presence of an intraductal component of carcinoma did not affect outcome, nor did the treatment techniques employed appear to have a differential effect.

Actuarial Analysis↗
PubMed1986

Adjuvant therapy in mixed mullerian tumors of the uterus.

We report 54 patients with mixed mullerian tumors of the uterus treated at Yale-New Haven Hospital from 1962 to 1983. Seven had previous pelvic irradiation. Twenty-five neoplasms were homologous and 29 were heterologous. The mainstay of therapy was surgery and radiation. By FIGO criteria 9 patients had stage IA disease, 31 stage IB, 6 stage II, and 8 patients had clinical extrauterine disease. Ten of forty-six patients (23%) with FIGO stage I and II disease had extrauterine disease found at surgery. No patient with extrauterine disease had prolonged survival. The 2-year disease-free survival with stage IA was 66%, with stage IB surgically confirmed 32%, and for stage II 33%. Surgically advanced disease in clinical stage I and II patients and recurrence were associated more frequently with a heterologous histology (67%). The small uterus with a less than 10-cm cavity had a better prognosis. Among 29 surgically confirmed stage I and II patients, 83% of recurrences appeared within 2 years (mean 16 months +/- 7 months). Patients who received both intracavitary radiation and external beam developed only 17.6% pelvic recurrence but this reduction in local recurrence was not associated with significant improved long-term survival. Six of eight patients treated with cis-platinum, Adriamycin, and dimethyl triazeno imidazole carboximide for persistent disease or for recurrence showed response for 4 to 24 months, none complete. Five patients were treated by radiation, surgery, and adjuvant chemotherapy (4 with Adriamycin-Cytoxan, 1 with Adriamycin-platinum). Four of the five (80%) are disease free from 36 to 60 months. These data and the experience of others support the need for a clinical trial with adjuvant platinum and Adriamycin in this disease.

Adult↗
PubMed1985

Solitary pelvic neural tumors with high steroid receptor content.

Two pelvic benign neural tumors, a neurofibroma and a neurilemmoma, were found to have high levels of cell nuclear estrogen receptors and both cytoplasmic and nuclear progestin receptors. A review of the literature reveals that neurogenic tumors occur predominantly in young women. This observation together with the recent findings of elevated sex steroid receptor proteins in meningiomas supports a hypothesis for the common hormonal dependence of neoplasms arising from the neural supporting tissues.

Adult↗
PubMed1985

Endodermal sinus tumor of the infant vagina.

A case of endodermal sinus tumor of the infant vagina is reported with long-term survival after successful therapy by surgery, chemotherapy, and radiation. The previous 26 reported cases are reviewed and the problems of therapy and long-term management are discussed. Therapy of these tumors should be monitored by alpha-fetoprotein radioimmunoassay.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1985

Fallopian tube carcinoma.

Twenty-one patients with fallopian tube carcinoma from Yale-New Haven Medical Center are reviewed. Most patients who died of disease did so in the first two years after diagnosis, even following complete resection, clearly indicating the need for adjuvant therapy. Negative second-look surgery did not provide assurance of permanent remission. There was a high recurrence rate with Stage I and completely resected Stage II and III disease (8 of 14 patients). Some recurrences occurred late, up to nine years after initial diagnosis. We recommend whole abdomino-pelvic radiation if no disease greater than 2 cm3 bulk exists after surgery. Chemotherapy may be an alternative to radiation as primary adjuvant treatment in early stage disease. Chemotherapy for unresectable disease or recurrent disease has shown palliation with occasional prolonged survival but no patient with recurrent disease survived longer than two years.

Adenocarcinoma↗
PubMed1984

Macroscopic and histologic tissue reaction to polydioxanone, a new, synthetic, monofilament microsuture.

A major contributing factor to failure in reconstructive tubal surgery is adhesion formation. It can be due to the presence of a foreign body primarily represented by suture material. A new, synthetic, absorbable suture material, Polydioxanone (PDS), was compared to polyglactin -910 (Vicryl). Microsurgical anastomosis of the bicornuate rat uterus served as a model. The right horn was anastomosed with 6-0 or 8-0 PDS and the left horn with Vicryl of the same diameter. At 3, 7, 14, 30 and 60 days after the procedure three to four animals were killed and the histologic reaction estimated and compared between the two horns. At 60 days the remaining animals were killed, and adhesion formation around the anastomosis site was recorded. PDS was found to be histologically more inert than Vicryl and was associated with a less intense acute and chronic inflammatory response than Vicryl. Similarly, macroscopic examination showed that the adhesion formation was quantitatively reduced in the PDS-treated horns, and most of those adhesions were avascular. The high inertness and absorbability suggest a practical application of PDS in infertility surgery.

Animals↗