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Biomedical subjects

P Costa

Publications and source records attributed to P Costa.

At least 127 records · Page 7Linked to original sources
PubMed1994

The temporoparietal fascial flap in reconstruction of the cranio-maxillofacial area.

An improved understanding of the vascular supply of the layers of the temporal fossa has increased the potentiality of reconstructive techniques involving this area. Each separate vascularized layer of this region can be used, yet the temporoparietal fascial flap is the more useful for treating a wide range of composite defects. It represents an ultra thin coverage which is useful in resurfacing exposed bone, tendons and vital structures such as nerves and vessels, in providing neovascularity as a recipient graft bed and in providing coverage or lining in major facial reconstructions. We describe our experience with the temporoparietal fascial flap which represents our choice for reconstructing composite defects in orbital, malar, auricular and cheek areas when what is required is a thin, pliable, well vascularized flap to carry a scalp or skin graft, to resurface exposed cartilage, bone and nerve, and to fill soft tissue contour defects. Illustrative cases from the authors' clinical experience are presented, to demonstrate various combinations of the temporoparietal fascial pedicle with other tissues in the reconstruction of the ear, eyebrows, eyelids, malar, cheek and parotid areas.

Adolescent↗
PubMed1994

[Molecular pathobiology in heart failure].

Heart failure is a pathophysiological state resulting from disturbed cardiac function. It is based on complex molecular processes, many of which are not fully understood. During heart failure adaptive mechanisms, that reinstall altered cardiac function, are activated. The main mechanisms are: a) Alteration of the structure and composition of myocytes by myocardial hypertrophy, reexpression of fetal and neo-natal proteins and the expression of certain proto-oncogenes; b) Activation of the neuroendocrinal system, specifically the sympathetic nervous system, renin-angiotensin-aldosterone system and vasopressin release; c) Activation of autocrine and paracrine systems. However, when these systems are activated beyond a certain limit they contribute to heart failure aggravation. This can also be promoted by alteration of the calcium metabolism inherent in heart failure. The synthesis of the counterregulator atrial natriuretic factor is also increased.

Atrial Natriuretic Factor↗
PubMed1994

[The instrumental and clinical laboratory follow-up of congenital hypothyroidism].

Early diagnosis, L-tiroxine therapy and adequate follow-up are determinant to remove the damages resulting from hormone deficiency in congenital hypothyroidism (CH). In order to achieve a better intellectual development, the authors suggest some guidelines for a correct follow-up on the basis of their personal experience on a population of 160 children with CH. These guidelines include monitored therapy, biochemical controls, instrumental investigations, clinical and auxological serial examinations. To better predict the mental outcome of these patients as adults, the authors propose a longer follow-up till adolescents, especially in the children with more severe hypothyroidism at diagnosis.

Child↗
PubMed1994

[Helicopter assistance in Sicily. Peculiar aspects of a 3-year experience].

OBJECTIVE: To report our experience concerning the first aid effected by helicopter both on scene (primary rescue) and interhospital transport of already treated patients requiring a highest level of diagnosis and treatment (secondary rescue), and the peculiar aspect appeared from the analysis of the obtained results, that is the predominance of the secondary rescue on the primary one. DESIGN: Retrospective evaluation of the interventions effected from August 1990 to February 1993. SETTING: Critical care units of a University teaching Hospital. MAIN RESULTS: 2669 interventions were effected: 2082 were secondary rescues (78%) and 587 primary rescue (22%). The patients actually transported by helicopter were 2419 (M = 1702; F = 717). The leading cause of non effected interventions was the deficiency of illuminated helicopter landing area; for the primary rescue, the main cause was the distance from the scene and the transport with land vehicles. The most frequent admission were for intensive care unit, neurosurgery, cardiac-surgery and neonatology, in only three towns. Indeed, the failing of Specialized Units involves the use of helicopter in interhospital transport for long periods, and this can remove time from primary rescue. CONCLUSION: As mentioned above, the peculiar aspect of our experience is the predominance of the secondary rescue on the primary one. It can be attributed particularly to the geographic and orographical characteristics of our region, together with the organization deficiencies in the field of emergency medical services.

Adult↗
PubMed1994

Double simultaneous hemodialysis during prolonged cardio-pulmonary resuscitation for hyperkalemic cardiac arrest. Case report.

A 57-year old male uremic patient developed a sudden cardiac arrest due to severe hyperkalemia. The cardiac arrest lasted 135 minutes and was initially unresponsive to conventional therapy. It was successfully treated by prolonged external cardiac massage, assisted ventilation and double simultaneous arteriovenous hemodialysis to rapidly decrease the high potassium level.

Cardiopulmonary Resuscitation↗
PubMed1994

[Renal nephrogenic nephroma: an little known exceptional tumor. Apropos of a case disclosed by xanthogranulomatous pyelonephritis].

The authors report a new case of an exceptional benign renal tumour: nephronogenic nephroma, composed of differentiation of the blastema into primitive nephronic formations. It raises the problem of differential diagnosis with adult Wilms' tumour and renal blastematosis. In this patient, it was associated with segmental xanthogranulomatous pyelonephritis, presenting in the form of psoïtis and an abscess of the thigh. Total nephrectomy was performed.

Abscess↗
PubMed1993

Extrathymic differentiation of T lymphocytes and natural killer cells from human embryonic liver precursors.

Liver cells were isolated on Ficoll/Hypaque gradients from embryos or fetuses at 6-10 weeks of gestation; 2-20% of the cells expressed CD45 or HLA class I surface antigens and 2-6% expressed CD7. Other T- or natural-killer (NK)-cell-lineage-specific markers were undetectable. Liver-cell suspensions cultured in the presence of phytohemagglutinin and recombinant interleukin 2 gave rise to large proportions of CD3+ lymphocytes expressing either alpha/beta or gamma/delta T-cell receptors. This occurred not only in bulk cultures but also when cells were cloned under limiting dilution conditions. Importantly, these figures were obtained also in embryos at 6-8 weeks of gestation, which is before colonization of the thymic rudiment by T-cell precursors. When the same liver-cell suspensions were cultured in the presence of irradiated H9 cells and recombinant interleukin 2 (either in bulk cultures or under cloning conditions), large proportions of cells (or clones) expressed surface CD16 and CD56 antigens and displayed a strong cytolytic activity against both NK-sensitive (K562) and NK-resistant (M14) target cells. In addition, liver-derived T or NK cells expressed functional receptor molecules since they could be activated via either CD3/T-cell receptor or CD16 surface antigens, respectively. Further fractionation of liver cells on the basis of CD45 antigen expression indicated that only CD45+ cells could give rise to T or NK cells in culture. Thus, CD45 can be used as a marker for identification of an early liver-cell population containing T- and NK-cell precursors. That T or NK cells were derived from male embryos and not from the mother was shown by PCR amplification of X and Y chromosomal sequences. Our present data may offer an in vitro model for extrathymic embryonic T-cell maturation that can be used to examine fundamental aspects of human T-cell development and function.

CD3 Complex↗
PubMed1993

A pilot study of hepatic artery floxuridine combined with systemic 5-fluorouracil and leucovorin. A potential adjuvant program after resection of colorectal hepatic metastases.

BACKGROUND: Most patients with colorectal carcinoma metastatic to the liver have relapses after surgical resection of hepatic metastases with failures divided equally between hepatic and extrahepatic sites. A pilot study was begun using a regimen combining intrahepatic floxuridine (FUDR) and systemic 5-fluorouracil (5-FU) and leucovorin (LV) to determine its safety and efficacy. METHODS: Because this was a pilot study, 21 patients with unresectable hepatic metastases from colorectal carcinoma were treated to assess the regimen's toxicity. Eight patients had liver metastases that were resected completely; then they received treatment. FUDR was given by hepatic arterial pump through a 14-day continuous infusion at 0.25 mg/kg/day. Systemic therapy consisted of LV 200 mg/m2 and 5-FU 280 mg/m2 using a bolus dose of 5-FU for 5 days with escalation of the 5-FU dose in separate patient cohorts. The maximally tolerated 5-FU dose was 325 mg/m2. RESULTS: The median survival in the 21 unresectable patients was 16 months with a partial response rate of 56% (10 of 18 evaluable patients; 95% confidence interval, 38-79%). The major systemic toxicity was diarrhea, Grade 3 or 4, in 54% of patients being treated in the 4-week regimen and 19%, in the 5-week regimen. The level of hepatic toxicity was similar to that in previous studies using intrahepatic chemotherapy alone, i.e., 48% of patients had a 200% increase in alkaline phosphatase levels and 10% had bilirubin elevations of more than 3.0 mg/dl (one patient had documented biliary sclerosis). All eight patients treated with adjuvant therapy were alive without disease after a median follow-up of 23 months. CONCLUSIONS: Systemic 5-FU and LV can be combined safely with intraarterial FUDR without loss of efficacy or increased biliary toxicity. Eight patients treated with this regimen as adjuvant therapy after liver metastasis resection were alive and disease-free after a median follow-up of 23 months.

Adult↗
PubMed1993

Ceftriaxone pharmacokinetics in elderly subjects and penetration into epididymis.

In a prospective study, the epididymal penetration of ceftriaxone was evaluated in order to use it in the treatment of orchi-epididymitis in men. A bolus intravenous dose of 1 g of ceftriaxone was administered to 15 patients hospitalized for surgery as part of treatment for prostatic adenoma or prostatic cancer. Nine successive blood samples were collected in the interval from 0 to 24 h after administration, and epididymis samples were taken 0.75 h after administration. Concentrations of drug in all samples were assayed by a reverse-phase-ion pairing high-performance liquid chromatography method with UV detection. The results showed that the pharmacokinetics of ceftriaxone in serum did not differ from those determined previously in healthy volunteers. The terminal half-life was 6.9 +/- 1.7 h, and the mean residence time 9.5 +/- 2.3 h. The volume of distribution was 0.144 +/- 0.018 1 kg-1 and the total body clearance 1.17 +/- 0.29 l h-1. The concentrations in tissue reached 27.2 +/- 6 micrograms g-1 in righ epididymis, and 25.4 +/- 6.2 micrograms g-1 in left epididymis. The tissue-versus-serum concentration ratios ranged from 0.175 to 0.545 (mean value, 0.295 +/- 0.099). The concentrations in serum and tissue observed in this study were in excess of the MICs for bacteria considered to be susceptible to ceftriaxone, particularly Neisseria gonorrhoeae and coliform bacteria.

Aged↗
PubMed1993

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

The concentration-time profiles of metabolites of moxisylyte, an alpha-adrenergic receptor blocking agent, in the plasma of 12 healthy volunteers were investigated after intravenous (iv) and intracavernous (ic) administrations. The study was conducted in open, randomized, Latin Squares. Plasma levels of moxisylyte and its biotransformation products were assayed by a specific high-performance liquid chromatography method with fluorescence detection. Three metabolites, unconjugated desacetylmoxisylyte (DAM), conjugated DAM, and conjugated monodesmethylated DAM (MDAM), were found in plasma. After iv administration, unconjugated DAM appeared in plasma in < 5 min; the formation of this metabolite is slightly lower after ic administration (half-life, 6.08 +/- 2.33 min). Maximum plasma levels (57.2 +/- 29.4 ng/mL) and area under the curve of concentration versus time (43.3 +/- 11.4 micrograms.h/L) were significantly lower after ic administration than after iv administration (352.8 +/- 287.6 ng/mL and 152.6 +/- 0.247 micrograms.h/L, respectively). For conjugated DAM, the time to reach the maximum concentration is significantly increased after ic administration (0.9 h instead of 0.46 h) and the maximum concentration is significantly decreased (163.5 ng/mL instead of 203.4 ng/mL). The other pharmacokinetic parameters show no change between the two routes of administration. The pharmacokinetic parameters computed for MDAM are in the same range after iv and ic administrations, and there are no significant statistical differences.

Adrenergic alpha-Antagonists↗
PubMed1993

Multiple-dose pharmacokinetics of moxisylyte after oral administration to healthy volunteers.

The pharmacokinetics of moxisylyte in plasma and urine was investigated after oral administration. Twelve subjects were treated orally, twice daily with 240 mg of the drug for 6 days; on day 7, the subjects received a last dose of 240 mg of moxisylyte. Moxisylyte was assayed in plasma and urine by a specific HPLC method with fluorimetric detection. Moxisylyte was absorbed rapidly and changed to its metabolites immediately after drug administration; unchanged moxisylyte was not found in plasma. Two metabolites were found in plasma and urine: conjugated desacetylmoxisylyte (DAM) and the conjugate of desmethylated DAM (MDAM). The pharmacokinetic parameters determined after the first oral administration were not modified on multiple dosing. The apparent elimination half-lives of conjugated DAM and MDAM were 2.3 and 3.5 h, respectively. Elimination of these two metabolites in urine averaged 50 and 10%, respectively.

Administration, Oral↗
PubMed1993

Adrenergic receptors on smooth muscle cells isolated from human penile corpus cavernosum.

The effect of the alpha-adrenergic blocker moxisylyte was examined on smooth muscle cells isolated from human corpus cavernosum, and compared with that of other adrenergic agents and papaverine. Isolated smooth muscle cells were shown to contract (reduction of the mean cell length) under noradrenaline and carbachol stimulations in a time-dependent and concentration-dependent manner (maximum at 30 seconds, EC50 [noradrenaline] = 5 nM., EC50 [carbachol] = 1 nM.). The contractile effect of noradrenaline was dose-dependently inhibited by moxisylyte (IC50 = 0.5 +/- 0.2 microM.) and by prazosin (IC50 = 0.9 +/- 0.2 microM.). The dose-response curves were parallel and no statistically significant difference could be shown between the IC50 values. The alpha 2-adrenergic antagonist tolazoline also inhibited noradrenaline-induced contraction, whereas the alpha-adrenergic agonist methoxamine did not change the mean cell length. As expected, isoproterenol caused relaxation of noradrenaline-precontracted cells by interaction with a beta 2-adrenergic receptor. Papaverine was also found to inhibit the contraction induced by noradrenaline in a dose-dependent manner (IC50 = 2 +/- 0.3 nM.). Tritiated-dihydroergocryptine (3H-DHE) specific binding was competitively inhibited by moxisylyte and prazosin with the same IC50 value of 0.01 microM. Methoxamine and tolazoline also inhibited this binding with lower affinity (IC50 = 0.1 +/- 0.02 microM.), while isoproterenol did not change specific binding. Scatchard plots from saturation experiments with 3H-DHE and with 3H-N-methyl scopolamine revealed the presence of 15 times more adrenergic than muscarinic binding sites (650,000 and 45,000 sites per cell, respectively). Together, these data support evidence for the presence of postsynaptic alpha 1-adrenergic receptors on smooth muscle cells from human corpus cavernosum. These receptors are coupled with the contraction of the cell and are blocked by the alpha 1-adrenergic antagonists moxisylyte or prazosin. They also show that the phosphodiesterase inhibitor papaverine and the beta-adrenergic agonist isoproterenol induced relaxation. This model constitutes a new approach to study the potential targets of the adrenergic agents in the erectile tissue.

Dose-Response Relationship, Drug↗
PubMed1993

Efficiency and side effects of intracavernous injections of moxisylyte in impotent patients: a dose-finding study versus placebo.

We assessed the efficiency and tolerance of the alpha-blocking agent moxisylyte in 2 double-blind studies versus placebo performed in 12 neurogenic patients with spinal cord lesions and in 61 patients presenting with either psychogenic impotence (30) or erectile dysfunction that was predominantly neither psychogenic, hormonal nor neurogenic (31). In each etiological group patients were randomized (according to latin square method) to receive 3 single doses (10, 20 and 30 mg.) of moxisylyte and a placebo. The erectile response was determined 5, 10, 15, 20 and 30 minutes after each injection. Whatever etiology of impotence and dosage tested, the erectile response induced by moxisylyte was significantly higher than the placebo-induced response. No difference occurred among the 3 doses. In 93% of the patients moxisylyte induced an erectile response, including tumescence in 6, partial rigidity in 16 and complete rigidity in 46. Thus, in 62 of 73 patients (85%) the drug allowed initiation of erection adequate for intercourse. Placebo induced such erection in only 25% of the cases and in 55% there was no response. Tolerance was good and no priapism occurred. Only 4 patients (5%) reported mild pain during injection but erections were never painful, 1 presented with moderate and transient hypotension at the 20 mg. dose and a painless prolonged erection was observed in 1 case after the lowest dose. Drugs such as moxisylyte should be given before less well tolerated drugs.

Adult↗
PubMed1993

Dose-related effect of moxisylyte on maximal urethral closing pressure in patients with spinal cord injuries.

The effects of single intravenous doses of 0.25, 0.50, and 0.75 mg/kg moxisylyte on maximum urethral closure pressure were evaluated in a placebo-controlled double-blind experiment in 20 patients with spinal cord injuries. Pharmacodynamic testing was performed until 30 minutes, and blood pressure was assessed until 60 minutes. Our findings showed a dose-dependent decrease in maximum urethral closure pressure. At each individual time point, the three doses differed significantly from placebo. Ten minutes after dose administration the maximum effect (48% decrease) was obtained with 0.75 mg/kg. A significant difference in favor of the highest dose was shown from 15 to 20 minutes after administration. According to these findings and because 0.75 mg/kg was as well tolerated as the two other doses, such a drop in pressure indicates that the alpha-blocking agent moxisylyte may be an effective means of decreasing urethral resistance, with obvious implications for the management of urinary obstruction.

Adolescent↗
PubMed1993

Rhabdomyolysis following life-threatening acute asthma attack.

The authors report a life-threatening, acute asthmatic attack in a young man, which was followed by rhabdomyolysis and acute myoglobinuria. A discussion of the possible rôle of the pharmacological treatment of asthma in initiating muscle damage is included, based on a review of the current literature.

Acute Disease↗
PubMed1993

Carboplatin and urothelial tumors.

The prognosis of advanced-stage bladder cancer is poor. Chemotherapy, particularly regimens including platinum salts, appears to increase survival moderately but at the cost of severe, mainly renal toxicity. Platinum is a major factor in this toxicity, and new platinum salts (chiefly carboplatin) have therefore been developed. Carboplatin has no renal toxicity at usual doses, and its use does not require concomitant hyperhydration. Its gastrointestinal, otologic, and general tolerability is excellent. In contrast, most patients develop thrombocytopenia, which can be important, but which is always transitory. The platelet count reaches its nadir (grade 2 or 3) at around day 20, and the leukocyte nadir (grade 2 or 3) occurs about day 19. Anemia is rare. The literature on the use of carboplatin for the treatment of advanced-stage urothelial tumors is reviewed. Carboplatin is used at doses varying between 200 and 400 mg/m2, administered in 28-day courses. Dose adjustment is based on serum creatinine level, creatinine clearance, nadir blood cell levels, or previous treatment, reflecting the wide disparity between different studies. Used alone, carboplatin achieved objective responses (ORs) in 14% of patients (3% complete responses, CRs, and 11% partial responses, PRs) in a total group of 327 patients included in 13 trials. In polychemotherapy various combinations of carboplatin with other agents have been reported, most frequently carboplatin/methotrexate/vinblastine; the OR rate was 63% (CR rate 19% and PR rate 44%) among 88 patients in four studies. These results confirm the relative efficacy of carboplatin in the treatment of advanced-stage urothelial tumors, particularly when it is combined with other agents. Its efficacy is similar to that of cisplatin, but it is far less toxic. A prospective, comparative trial will be necessary to confirm these data. The pharmacokinetic behaviors of the two platinum salts are markedly different, as carboplatin does not undergo tubular metabolism. The efficacy of carboplatin could be optimized by adapting the dosage to the glomerular filtration rate, which is a more accurate method than extrapolation from the serum creatinine or creatinine clearance values. This has been shown in the case of nonseminomatous germ cell tumors. Calculation of the optimum carboplatin dose should now be applied to urothelial tumors. The general and renal tolerability of a platinum salt is an important element of choice when the efficacies are equivalent. These considerations fully warrant further clinical trials of carboplatin.

Antineoplastic Combined Chemotherapy Protocols↗