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Biomedical subjects

P Costa

Publications and source records attributed to P Costa.

At least 19 recordsLinked to original sources
PubMed1992

Treatment of metastatic malignant melanoma with dacarbazine plus tamoxifen.

BACKGROUND: Endocrine factors may affect the clinical course of malignant melanoma and the response to the treatment of this disease. The presence of estrogen receptors in melanomas has been suggested, and occasional responses to antiestrogen therapy have been reported. METHODS AND RESULTS: We randomly assigned 117 patients with metastatic malignant melanoma to treatment with dacarbazine alone or dacarbazine in combination with tamoxifen. The overall rate of response, measured objectively, was higher (28 percent vs. 12 percent, P = 0.03) and survival was longer (median, 48 vs. 29 weeks, P = 0.02) among the patients who received dacarbazine plus tamoxifen than among those who received dacarbazine alone. Among women, both the response rate (38 percent vs. 10 percent, P = 0.04) and the median survival (69 vs. 30 weeks, P = 0.008) were better with dacarbazine plus tamoxifen than with dacarbazine alone, whereas among men the differences were smaller and not statistically significant. Among the patients given dacarbazine alone, there were no significant differences between women and men in response rate (10 percent vs. 13 percent) or survival (30 vs. 27 weeks), whereas among those given dacarbazine plus tamoxifen, women had better outcomes, as indicated by both response rate (38 percent vs. 19 percent, P = 0.15) and survival (69 vs. 31 weeks, P = 0.02). When we analyzed the Quetelet body-mass index (the weight in kilograms divided by the square of the height in meters) as an indirect indicator of the levels of endogenous estrogens in postmenopausal women and in men, survival was not affected by the body-mass index in the group given dacarbazine alone, whereas in the group given dacarbazine plus tamoxifen, survival was longer among patients whose Quetelet index was above the median value than among those with a Quetelet index lower than the median value (60 vs. 26 weeks, P less than 0.001). CONCLUSIONS: In the treatment of metastatic malignant melanoma, dacarbazine plus tamoxifen is more effective than dacarbazine alone, as indicated by both the response rate and the median survival; the difference in efficacy is among women.

Adult↗
PubMed1992

Moxisylyte plasma kinetics in humans after intracavernous administration.

Obtaining and sustaining an erection are common problems for the male spinal cord injury patient. Intracavernous injection of vasoactive substances offers a new treatment option but it must be approached with caution in this population. In this work, the use of an alpha-adrenergic blocking agent, moxisylyte, after intracavernous administration for complete paraplegic patients with erectile impotence is described. During this study, the pharmacokinetic profile of moxisylyte has been defined. Unchanged moxisylyte is not found in plasma, this drug is immediately metabolized after administration. Three metabolites were found in plasma: desacetylmoxisylyte (DAM), conjugated DAM, and conjugates of desmethylated DAM (MDAM). Maximum plasma levels of 72.3 ng ml-1, 301.4 ng ml-1, and 88.8 ng ml-1 are obtained 0.22 h, 0.9 h, and 2.08 h after drug administration for these three metabolites, respectively. The elimination half-lives are 0.89 h, 2.16 h, and 5.32 h and the MRT, 1.38 h, 3.23 h, and 8.45 h, respectively. No side-effects were noted, only one patient presented sleepiness. Successful erections (10 to 25 min) were obtained in all patients and no priapism was noted.

Adult↗
PubMed1992

Pharmacokinetics of moxisylyte in healthy volunteers after intravenous and oral administration.

The concentration-time profiles of metabolites of moxisylyte, an alpha-blocking agent, in the plasma and urine of 12 healthy volunteers were investigated after intravenous (iv) and oral (two formulations) administration. The study was conducted with an open, randomized Latin squares design. Plasma and urine levels of moxisylyte and its biotransformation products were assayed by a specific HPLC method with fluorescence detection. Plasma levels declined in a monophasic or biphasic pattern depending on the subject. Two metabolites, conjugated desacetylmoxisylyte (DAM) and conjugated monodesmethylated DAM (MDAM), were found in plasma and urine. Unconjugated DAM was found in plasma only after iv administration. The apparent elimination half-lives of unconjugated DAM, conjugated DAM, and MDAM were 0.86, 1.7, and 3 h, respectively. The total amounts of metabolites (expressed as the equivalent of DAM) excreted in the urine were 75% after i.v. administration and 68 and 69% after oral administration of the two formulations. Oral absorption appeared to be complete for the two treatments. There was no statistical difference between the two oral formulations studied.

Administration, Oral↗
PubMed1992

Disposition of roxithromycin in the epididymis after repeated oral administration.

The epididymal penetration of roxithromycin was studied in order to evaluate the drug for use in the treatment of epididymo-orchitis. Seventeen patients hospitalized for surgery as part of treatment for prostatic adenoma or prostatic cancer were premedicated orally with roxithromycin 150 mg bd for three days followed by 150 mg pre-operatively (3 h before surgical incision). Roxithromycin concentrations in serum and epididymis were determined by microbiological assay. The mean epididymal concentrations were 6.48 +/- 4.88 and 5.98 +/- 3.92 mg/kg for left and right epididymis respectively and the corresponding mean tissue/serum ratios 0.88 +/- 0.57 and 0.84 +/- 0.53. The wide intersubject variation in the concentration of roxithromycin found in serum and tissue is commonly seen with other macrolide antibiotics. The concentrations observed in this study in serum and tissue were greater than the MIC90s for Chlamydia trachomatis (0.25 to 1 mg/L), and Ureaplasma urealyticum (0.5 mg/L).

Adenoma↗
PubMed1992

Clinical study of the longitudinal deformation of the flaccid penis and of its variations with aging.

The length changes of the flaccid penis provoked by a maximum manual stretching of the glans have been measured in 905 men in order to study its biomechanical qualities. Our study shows that the flaccid penis is deformable, extensible and elastic in its longitudinal axis. The analysis of the variations of these biomechanical properties with aging shows a significant decrease. Thus, the biomechanical behavior of the flaccid penis during stretching is highly different in young men and old men. This distortion difference according to age proves the physiological importance of the penile distortion since impotence significantly increases with age. As the vascular mechanisms may be disregarded during flaccidity, these penile physical features of the flaccid penis are only due to tissue mechanisms. Consequently, any distortion loss would reflect a tissue impairment, very likely a progressive senile fibrosis of cavernous tissues.

Adolescent↗
PubMed1992

Biochemical modulation of bolus fluorouracil by PALA in patients with advanced colorectal cancer.

PURPOSE: N-(phosphonacetyl)-L-aspartic acid (PALA) is a pyrimidine synthesis inhibitor that modulates fluorouracil (FU) cytotoxicity. Two previous studies of patients with colorectal carcinoma documented complete response (CR) and partial response (PR) rates of 40% and 43% using weekly low-dose PALA followed by a 24-hour FU infusion. We investigated whether comparable results could be obtained with biochemical modulation by low-dose PALA using bolus instead of infusional FU. PATIENTS AND METHODS: Forty-five patients without prior chemotherapy who had advanced colorectal carcinoma were treated with PALA 250 mg/m2 followed 24 hours later by bolus FU at three dose levels, 600, 700, 800 mg/m2, repeated weekly for 6 weeks followed by a 2-week break. RESULTS: The CR and PR rate was 15 of 43 patients or 35% (95% confidence interval [CI], 21% to 49%), with an overall median survival of 18 months. Grade 3 or 4 diarrhea was the major toxicity observed in 24% of patients receiving FU at 700 mg/m2 and in 43% of patients receiving 800 mg/m2. Hematologic toxicity was observed only with an FU dose of 800 mg/m2, and 29% (four of 14) of patients developed grade 4 leukopenia. We also noted the development of ascites in six patients, mild hyperbilirubinemia in 16 patients, and a decreased albumin level in 22 patients; these abnormalities occurred more frequently in responding patients. CONCLUSIONS: The observed response rate, median survival, and toxicity in this study are similar to those obtained with PALA plus infusional FU and with other methods of FU modulation. Larger phase III studies are needed to compare bolus FU/PALA regimens with other PALA and non-PALA-containing combinations. Our future focus will be attenuate this regimen's toxicity while maintaining or improving its response rates and survival.

Adenocarcinoma↗
PubMed1992

[Therapeutic indications and complementary explorations in benign prostatic hypertrophy: significance of simultaneous recordings].

Dysuria due to obstruction by benign prostatic hypertrophy causes an increase in the bladder work and constitutes the origin of alterations in the bladder wall. Although initially reversible, the progression towards fibrosis makes recovery increasingly incomplete the longer the treatment is delayed. The detection and evaluation of increased bladder work in the presence of early obstruction allows treatment to be instituted early in the natural history of the disease. Although clinical examination may be suggestive of bladder neck obstruction, it is neither characteristic of the bladder repercussions nor sufficient to define a population at risk. Similarly, voiding urethrography, uroflowmetry or cystomanometry, taken separately, are unable to assess bladder work early in the disease. However, bladder work can be studied by recording the voiding intravesical pressure (measured by a suprapubic catheter) in relation to the urine flow (measured by uroflowmetry). By studying the variations in voiding pressure in relation to initiation of micturition, a parameter can be defined which is useful for the therapeutic indication: the PVOP (pre-voiding opening pressure of the bladder neck), which is able to distinguish 2 mechanisms of obstruction: "compression" characterised by a raised PVOP, as in the case of benign prostatic hypertrophy, and "stenosis", with an unchanged PVOP, as in the case of urethral stricture. Re-evaluation after prostatectomy shows a return to normal of the PVOP. The difficulty of routinely inserting a suprapubic catheter has led to the development of indirect approaches, particularly voiding hydrodynamic morphological or transrectal ultrasonographic methods.

Humans↗
PubMed1992

[Postoperative rectoprostatic fistulas. Report of 2 cases. Review of the literature].

The authors report two cases of acquired prostatorectal fistulae after TURP, which were treated by a Kraske approach. They review the literature of iatrogenic fistulae and all of the techniques of approaching the prostatorectal region. If the bladder drainage is always necessary and may be sufficient in as much as 34% of the patients, the need for a colostomy and the choice of the approach is discussed.

Aged↗
PubMed1992

A new transthyretin mutation associated with amyloid cardiomyopathy.

In transthyretin (TTR) a new mutation (TTR-Thr45) has been identified in a patient with familial amyloidosis characterized clinically by prominent cardiomyopathy and the absence of peripheral neuropathy. Comparative peptide mapping by high-performance liquid chromatography of the patient's plasma TTR together with normal TTR showed the presence of an abnormal tryptic peptide in the patient's TTR. The sequence of this peptide (peptide 6, residues 36-48) demonstrated the presence of a threonine-for-alanine substitution at position 45. This change can be explained by a single base change of adenine for guanine in the Ala-45 codon and was demonstrated directly by DNA sequence analysis of PCR-amplified exon 2 of the TTR gene; allele-specific oligonucleotide hybridization both in the patient and in fixed heart tissue from his aunt confirmed the base change. The TTR-Thr45 mutation is a new variant TTR found associated with cardiomyopathy.

Amino Acid Sequence↗
PubMed1992

[Efficacy and safety of amrinone in the treatment of heart insufficiency in intensive care].

The authors describe the results obtained treating with amrinone for 48 hours 11 patients with acute heart failure. The patients (4 males and 7 females), age range between 50 and 82 years) received an initial bolus of 0.75 mg/kg followed by and infusion which on average was of 5.82 +/- 1.06 (SD) micrograms/kg/min. Besides a subjective and objective clinical improvement they could observe a quick and remarkable improvement of the main hemodynamic parameters (cardiac index, cardiac output, pulmonary capillary wedge pressure, mean pulmonary pressure). The tolerability of the drug was good, except for a decrease in platelet, already described in literature. In conclusion, the Authors consider amrinone a very interesting drug for its positive inotropic and vasodilating activity and because it does not cause an increase of the myocardial oxygen consumption.

Acute Disease↗
PubMed1992

[Role of oxygen venous saturation monitoring and CAVH in the multiple organ failure syndrome. Description of a clinical case].

A 42 year old man was admitted to the intensive Care Unit with signs and symptoms of septic shock, associated with adult respiratory distress syndrome (ARDS), jaundice and acute renal failure. In order to support different organs failures mechanical ventilation (IPPV, PSV, CPAP), continuous arteriovenous hemofiltration were affected, and continuous intravenous infusion of dopamine and dobutamine was started. After and during application of these therapeutic measures, continuous monitoring of mixed venous blood oxygen saturation (SvO2) was applied by Swan-Ganz fiber optic catheter in the pulmonary artery. Monitoring of SvO2 represented a useful means to guide inotropic therapy and to assess the hemodynamic effects of CAVH and mechanical ventilation. The case reported emphasized the role of continuous venous oximetry in multiple organ failure syndrome.

Adult↗
PubMed1991

A new syndrome: ascites, hyperbilirubinemia, and hypoalbuminemia after biochemical modulation of fluorouracil with N-phosphonacetyl-L-aspartate (PALA)

OBJECTIVE: To report a new syndrome of ascites, hyperbilirubinemia, and hypoalbuminemia after treatment with N-phosphonacetyl-L-aspartate (PALA) and fluorouracil for metastatic colorectal cancer. DESIGN: Retrospective analysis. SETTING: Regional cancer treatment center. PATIENTS: Forty-four previously untreated patients with metastatic colorectal cancer in a phase I-II trial of PALA-fluorouracil. MEASUREMENTS AND MAIN RESULTS: One or more transient hepatic abnormalities frequently occurred in 15 of the 17 responding patients. Within the first 10 weeks of treatment, 5 patients developed ascites, 12 had a decrease in the serum albumin level, 6 developed bilirubin elevations, and 7 had transaminase elevations, all in the presence of a complete or partial tumor response. Prolongations of the prothrombin time and elevations of serum glucose levels were also seen. CONCLUSIONS: An unusual syndrome of ascites, hyperbilirubinemia, and hypoalbuminemia is associated with a PALA-fluorouracil regimen. These abnormalities, which may be related to decreased hepatic protein synthesis, occurred more often in patients whose tumor was responding to chemotherapy. Clinicians must recognize that in patients undergoing chemotherapy with these agents, ascites and elevated liver function tests may be secondary to drug administration and are not necessarily due to disease progression.

Aged↗
PubMed1991

Cerebellar syndrome in adult celiac disease with vitamin E deficiency.

We studied a woman with adult onset celiac disease complicated by a cerebellar syndrome that progressed despite the resolution of the malabsorption symptoms with a gluten free diet. The patient presented vitamin E deficiency and the cerebellar symptoms improved with vitamin E therapy. This case supports the possible role of this deficiency in the development of the neurological complications of celiac disease.

Adult↗
PubMed1991

Altered tobramycin pharmacokinetics during chemoprophylaxis in bladder surgery.

The effect of bladder surgery on the pharmacokinetics of tobramycin in hospitalized patients was studied. Fourteen patients with vesical neoplasia undergoing urinary tract surgery were given tobramycin in a dose of 2 mg/kg of body weight. Each patient received the dose at the induction of anesthesia, about 1 h before surgical incision. For seven patients, the drug was also administered 3 weeks later when nutritional conditions were normal. The pharmacokinetic parameters were determined by a two-compartment open model. Except for renal clearance, no significant difference appeared between pharmacokinetic parameters determined from serum data during peri- and postoperative periods. During this work, tobramycin excretion in urine was studied. Twenty-four hours after drug administration, the mean urine tobramycin levels were 25.5 +/- 9.06 and 41.6 +/- 21.5 micrograms/ml after peri- and postoperative administration, respectively; these values were higher than the MICs for most urinary tract pathogens. Seventy-two hours after perioperative administration, the mean value was still elevated (3.54 micrograms/ml), but 72 h after postoperative administration, the urinary tobramycin concentration was not detectable. The percentages of tobramycin recovered unchanged in urine were 54 and 79% after peri- and postoperative administration, respectively. When tobramycin was administered during surgery, a long terminal log-linear phase, with a mean half-life of 25.6 h, was detected. The ratio of renal clearance to total body clearance was 0.52 and 0.79 after peri- and postoperative administration, respectively.

Aged↗
PubMed1991

Reduction of bronchial responsiveness to methacholine after mitral valve replacement.

Sixteen patients with mitral valve disease, in whom bronchial hyperresponsiveness to methacholine had been detected shortly before mitral valve replacement (MVR), were reevaluated 35 +/- 1.5 months after MVR. In 9/16 patients there was a significant (greater than 1.5 fold) increase in bronchial provocation dose of methacholine (PD20FEV1) after MVR. In the same patients there was a significant increase in vital capacity (from 69.6 +/- 5 to 75.8 +/- 5.2% of predicted, p less than 0.01), a significant decrease in cardiothoracic ratio and in radiologic score for lung edema (from 64.3 +/- 2.9 to 56 +/- 2.1, p less than 0.01 and from 38 +/- 4.5 to 14.6 +/- 2, p less than 0.001, respectively). In all the patients the increase in PD20FEV1 was not related to any change in spirometric values but it was related to the decrease in cardiothoracic index (r = 0.72, p less than 0.01) and in radiologic score for lung edema (r = 0.61, p less than 0.05) observed after cardiosurgery.

Bronchial Provocation Tests↗