Biomedical subjects
Publications and source records attributed to P Costa.
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.
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.
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.
Twenty-four patients ranging from 28 to 56 years of age with Garden grade III or IV fractures of the femoral neck are reviewed after treatment by intertrocherantic valgus osteotomy and Richards sliding compression hip screw. The rationale behind this treatment, the operative technique, and the choice of internal fixation device are all discussed. All patients were followed up after more than 2 years so that any late complications could be documented. The results were evaluated using both the Merle d'Aubigné procedure and radiographic examination: 12 (50%) were rated excellent, 5 (20.8%) good, 2 (8.4%) fair, and 5 (20.8%) poor. The unsatisfactory results are analyzed in detail, attributable to non-union in 2 cases (due to technical error), avascular necrosis in 4 cases (2 were limited and well-tolerated by the patients; 2 were early and massive and necessitated prosthetic replacement), and infection in one case. Even though valgus osteotomy and internal fixation fill a gap in the treatment of femoral neck fractures in adults by yielding good results with a conservative method, they are very demanding surgical procedures, requiring anatomical reduction, atraumatic technique, precise calculation of the valgus angle, and precise placement of the internal fixation device.
Thirty polytraumatized patients underwent immediate osteosynthesis of two or more long bone fractures for a total of 82 operations (plus an additional 14 for pelvis, hand, and foot fractures). Since 1983, according to the modern and rational concepts of "all at one time treatment", open fractures as well as associated closed lesions are stabilized immediately if the patient's general condition permits. This type of procedure requires adequate facilities as well as availability of and collaboration between teams of specialists, but it is inarguably advantageous for the patient (relief of pain, drastic reduction in the rate of embolism, improvement of respiratory and circulatory function, only one anesthesia), the surgeons (operation technically easier and shorter), and the ancillary medical personnel (easier nursing, rapid functional rehabilitation). The methods of osteosynthesis should be carefully selected in order to guarantee stability, rapid application, and low aggressiveness. The use of plates and screws is limited, while external fixation is employed frequently. Interlocked intramedullary nailing is adopted with increasing frequency. Review of cases treated by this method shows considerable improvement in terms of healing, functional recovery, and resumption of social and occupational activity.
The Authors report on their experience about SvO2 continuous monitoring in order to find out the best therapeutic answer to inotropic drugs, knowing that, at constant values of SaO2 and Hb, possible variations of SvO2 reliably correspond with parallel variations of cardiac index (IC). Two groups of 15 patients each, suffering from low out-put syndrome, have been studied; patients have been treated with inotropic therapy based on Dobutamina and Amrinone. The 2 groups only differed from each other for the kind of monitoring: the first group was exposed to intermittent measurements of the cardiac out-put, while the second group was exposed to continuous monitoring of SvO2. Analysing the obtained results, the Authors notice not only a close correlation between the improvement of SvO2 and IC, but also a significant rediction in time required to dose drugs, owing to the constant help provided by on-line monitoring of SvO2. (table; see text)
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Norfloxacin, a "second generation" compound of the quinolone group, was administered orally, before surgery, every 12 h during successive three-day periods at dose of 400 mg to ten patients hospitalized for prostatic adenoma or for prostatic cancer. On the day of surgery, a 400 mg-last dose was administered. Unchanged norfloxacin was assayed by high performance liquid chromatography with fluorescence detection. The Cmin value was 1.2 +/- 0.77 mg/l. Concurrent norfloxacin concentrations in plasma and epididymal tissue (left and right) were determined, about 4 h after the last drug intake, the epididymal level was 3.4 +/- 1.9 micrograms/g. This value was above the MIC90 for most sensitive organisms. The ratio (+/- SD) of drug concentration in epididymal tissue and in plasma was 3. 74 +/- 2.10 (range 1.66-10.2). The epididymal level of norfloxacin was strongly correlated with, area under curve (p less than 0.001) and plasma concentration (p less than 0.01).
The treatment of diaphyseal and metaphyseal fractures of the humerus is often controversial, especially when these fractures are complex and/or unstable (i.e. comminuted, segmental, or with a butterfly fragment). The authors review the indications, advantages, and disadvantages of various open and closed procedures, concluding that a combination of internal and external fixation is a valid treatment for these fractures. The purpose of the external fixation is immediate stabilization of the fracture, which is difficult if not impossible with intramedullary internal fixation alone. Internal fixation devices (Rush rods or "anchor" nails introduced by closed means) make it possible to align the fracture, facilitating application of the external fixator, and at the same time promote rapid healing. Fractures treated by this method healed in an average of 2 1/2 months, without residual functional limitations of the shoulder or elbow.
The management of patients with neurological dysfunctions of the bladder and the sphincter is considerably modified in recent years. The concept of "neurogenic bladder" has evolved due to new fundamental neurophysiological research following the advances of urodynamic investigations and medical imaging techniques as well as progress in drug therapy, surgical treatment and re-education. The current management of a traumatic paraplegia should therefore be prospective and must try to determine prognostic factors.
The expression of cytochrome P450 genes directly within target cells is an important determinant of human susceptibility to cancers, birth defects, and other chemically initiated diseases. One pivotal gene, CYP1A1, codes for an inducible cytochrome P450 isozyme (P450IA1) responsible for the bioactivation of numerous carcinogenic polycyclic hydrocarbons and aromatic amines. In this study, we used the polymerase chain reaction (PCR) to amplify endogenous P450IA1 mRNA transcripts in a variety of human and rat tissues from different stages of development. The PCR approach greatly enhanced detection sensitivities over those previously achieved and permitted characterization of constitutive as well as induced P450IA1 mRNA expression patterns in specific cell types and organs and during early gestational stages. P450IA1 mRNAs are expressed constitutively in the rat as early as day 15 of fetal liver development and increased in level with increasing developmental age. Transplacental treatment of fetal rats with 3-methylcholanthrene resulted in marked increases in P450IA1 mRNA levels, and responsiveness to the inducer also increased in concordance with developmental age. Comparatively lower constitutive and induced levels of the mRNA were detected in rat lung and kidney, but no P450IA1 mRNA was detected in the rat testis. PCR results obtained from experiments with human tissue samples demonstrated the presence of P450IA1 transcripts in whole organs, in purified cell fractions (lymphocytes, macrophages), and in fetuses as early as day 45 of human gestation. Data from cell culture studies indicated markedly higher levels of P450IA1 PCR product in human pulmonary alveolar macrophages following treatment with the inducing agent beta-naphthoflavone. These results underscore the potential role of P450IA1 as a key determinant of individual susceptibility to tissue-specific and developmentally related cancers associated with certain environmental chemical exposures.
The possibility of utilizing agroindustrial wastes in the production of edible, high-quality products (e.g., mushrooms) implies the risk of bringing toxic substances, such as heavy metals, into the human food chain. Thus, growth in the presence of cadmium and cadmium accumulation limits have been studied in the industrially cultivated fungus P. ostreatus. Fruit body production is substantially unaffected in the presence of 25, 139, and 285 mg Cd/kg of dried substrate. Cadmium concentration in fruit bodies is related to cadmium substrate level, the metal being present at higher levels in caps (22-56 mg/kg dry wt) than in stems (13-36 mg/kg dry wt). Concentration factor (CF), very low in the controls (about 2), further decreases in treated specimens. The presence of a cadmium control mechanism in this fungi species is suggested. Fruit body cadmium levels could, however, represent a risk for P. ostreatus consumers, according to FAO/WHO limits related to weekly cadmium intake.
Thirty-six patients with preoperative renal dysfunction were studied to evaluate the effects of dopamine (D) and dopamine-nitroprusside (DN) on renal function during cardiopulmonary bypass (CPB). No differences from the control group (C) were found in creatinine clearance, fractional sodium excretion, osmolarity and free-water clearance. Sodium output/intake ratio during CPB was higher in group D than in groups C and DN (P less than 0.05); water output/intake ratio was higher in group D than in group C (P less than 0.05). Urine lysozime levels and alpha-glycosidase/creatinine ratios increased similarly in the three groups, suggesting ischemic tubular cell damage. No patients showed acute postoperative renal failure or a worsening of their renal dysfunction. The data suggest an increased water and sodium excretion during CPB with a dopamine infusion, possibly resulting from a renal vasodilator effect that was abolished by simultaneous nitroprusside administration.
Amyloid fibril material was extracted from autopsy material of a patient who died from progressive cardiac failure at age 64. He had enlarged heart on routine X-ray at age 47 and the first symptoms of cardiac failure at age 62. Fractionation of the fibril material resolved peptide fragments immunoreactive with anti-human transthyretin (TTR). One of the peptides was further purified by high-performance liquid chromatography (HPLC) and subjected to tryptic peptide mapping along with TTR isolated from the patient's serum. In both instances, sequencing procedures revealed, in addition to the normal peptide 12 (residues 105-126), an abnormal peptide with an isoleucine for valine substitution at position 122. This substitution has been described previously in a patient with systemic senile amyloidosis (SSA) homozygous for this variant. The results question whether SSA is a clinical entity related to TTR Ile 122 with phenotypic expression in the homozygous condition.
Neutrophil oxidative metabolism, C3d and beta 2 microglobulin levels, were assessed in nine consecutive patients undergoing cardiopulmonary bypass surgery with polypropylene hollow fiber oxygenators for open cardiac operations. Generation of oxygen free radicals by neutrophils was measured as luminol-enhanced chemiluminescence after stimulation with opsonized Zymosan and phorbol myristate acetate. A significant increase in light emission was detected by using both of the chemiluminescence stimulators. Moreover, a remarkable and significant increase in C3d levels was found already at 10 min. Conversely minimal changes in levels of beta 2 microglobulin were detected during cardiopulmonary bypass surgery. These data suggest that the impact of the patient blood with the foreign surface of cardiopulmonary bypass results in activation of phagocyte cells with increased potential in oxygen consumption. These effects could be partially complement-mediated.
An 8-center, double-blind, placebo-controlled trial of 39 patients with benign prostatic hypertrophy was conducted to assess the effects of prazosin HCl treatment on functional urologic variables after a treatment period of 4 weeks. The randomized groups were comparable for demographic variables and symptoms, except for the mean residual urinary volume, which was significantly higher in the prazosin HCl group. Prazosin HCl elicited statistically significant improvements in the mean prostatic urethral pressure and prostate area (Mann-Whitney U test: p = 0.001 for both variables as compared with the placebo group). Functional bladder capacity also improved significantly in the group receiving the test drug (Mann-Whitney U test: p = 0.05, as compared with the placebo group). Clinical improvements were also observed in the mean maximum urinary flow, decreased nocturia frequency, and residual urinary volume. Patient preference significantly favored the prazosin HCl treatment (Mann-Whitney U test: p = 0.001). Seven patients on prazosin HCl and 5 receiving placebo reported one or more side effects during the trial phase; these were mild to moderate and disappeared or were tolerated. No statistically significant effects on blood pressure or heart rate were observed.
Primary total hip replacement in femoral neck fractures is still controversial. This report presents the findings of a study of 42 femoral neck fractures treated with cemented arthroprosthesis with an average follow-up of five years. The patients were divided into two groups according to the type of prosthesis, the reaming and cementing techniques, and the type of operating room. Each group had positive results in about 80% of the cases, testifying to the fact that arthroprosthesis is a valid method of treatment provided that the following procedures are scrupulously carried out: the preparation of the patient, the choice and implantation of the prosthesis, and the functional and psychological rehabilitation of the patient.
In this study we examined the differential hepatic expression of four phenobarbital (PB)-inducible rat cytochrome P450 genes, CYP2B1, CYP2B2, CYP2C6, and CYP3A1. The mRNAs encoding these cytochromes were analyzed in the liver with respect to PB responsiveness, developmental expression, and in situ localization. Utilization of the polymerase chain reaction enabled assessment of specific hepatic mRNA expression patterns during early development that were not detectable with standard Northern blot or slot-blot procedures. The polymerase chain reaction data demonstrated that fetal liver from day 15 of gestation was responsive to the inductive effects of transplacental PB administration. Both constitutive and PB-induced levels of each mRNA increased with increasing developmental age, reaching maximal levels approximately 3 weeks postpartum. An exception to this trend was observed for rats of gestational day 22, which exhibited transiently increased constitutive levels of CYP2B1, CYP2B2, and CYP3A1 mRNAs, such that PB-induced levels were not elevated over those observed in untreated animals. In situ hybridization data, obtained with livers form 6-week postpartum animals, revealed striking differences in regional distributions among the cytochrome P450 transcripts. Whereas patterns of PB-induced expression of CYP2C6 mRNAs were relatively homogeneous across the hepatic lobule, CYP3A1 mRNAs in PB-treated livers demonstrated marked centrilobular localization. These results were in contrast to data obtained previously for PB-inducible CYP2B1 and CYP2B2 mRNAs, which were distributed homogeneously across the hepatic lobule except for cells in the immediate vicinity of the periportal tract.