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Biomedical subjects

J Costa

Publications and source records attributed to J Costa.

At least 181 records · Page 10Linked to original sources

Treatment of chronic hepatitis B in children with recombinant alfa interferon. Different response according to age at infection.

The objective of this study was to investigate the possibility of predictive factors of response to treatment with interferon in children with chronic hepatitis B virus infection. We analyzed the influence on the response rate of age, sex, mode of acquisition of infection, severity, and duration of disease in 16 children with chronic hepatitis B treated with 3 MU of recombinant alpha-interferon 2b three times a week for 6 months. Six months after the end of treatment, eight patients (50%) had cleared HBV DNA, seroconverted to anti-HBe and normalized serum transaminase values. Response was significantly higher in those whose serum transaminase levels were > 100 IU/liter before treatment (70%) and those infected after birth (72%) compared with those with lower serum transaminase levels (16%) and those infected at birth (7%). Our findings indicate that a 6 month course of low dose interferon (3 MU) is highly effective in children with horizontally transmitted chronic hepatitis B virus infection, but noneffective in children infected at birth.

Adolescent↗

Cellular schwannomas of the intracranial and intraspinal compartment: morphological and immunological characteristics compared with classical benign schwannomas.

The concept of cellular schwannoma as an unusual benign tumor is well established for peripheral nerves but has never been tested in neurosurgical series. In order to test the validity of this concept in cranial nerves and spinal roots we performed an analysis of the clinical and morphological characteristics of 12 cellular and 166 classical benign schwannomas. Immunohistochemical detection of antigen expression in Schwann cells including proliferating cell nuclear antigen (PCNA) was also performed. This study shows that cellular schwannomas in neurosurgical series manifest at a lower age than the classical benign variant and occur mainly in the spinal roots. Mitotic activity and sinusoidal vessels appear more frequently in cellular schwannomas and constitute with high cellularity, the most valuable criteria separating both entities. The postoperative course in both types of tumors was free of metastases or sarcomatous changes. Immunoexpression of S-100 protein, vimentin, epithelial membrane antigen and glial fibrillary acidic protein is not statistically different between the two variants. In contrast, PCNA is more highly expressed in cellular schwannomas. These These results confirm the concept that cellular schwannomas are a clinico-pathological variant of benign schwannomas and provide significant support for the introduction of this entity in neurosurgical oncology.

Adult↗

Propofol vs midazolam in short-, medium-, and long-term sedation of critically ill patients. A cost-benefit analysis.

The purpose of this study was to evaluate and compare the clinical effects, safety, and economic cost of propofol and midazolam in the sedation of patients undergoing mechanical ventilation in the ICU. Eighty-eight critically ill patients were studied and randomly allocated to receive short-term (less than 24 h), medium-term (24 h to 7 days), and prolonged (more than 7 days) continuous sedation with propofol (n = 46) or midazolam (n = 42). Mean doses required were 2.36 mg/kg/h for propofol and 0.17 mg/kg/h for midazolam. Patients in the group receiving propofol showed a percentage of hours of sedation at the desired level (grade 2, 3, 4, or 5 on the Ramsay scale) of 93 percent, compared with 82 percent (p < 0.05) in the group receiving midazolam. Both agents were considered safe with respect to the induction of adverse reactions during their use in prolonged sedation. Recovery after interrupting sedation was significantly faster in patients treated with propofol than in those sedated with midazolam (p < 0.05). Recovery of total consciousness was predictable according to sedation time in propofol-treated subgroups (r = 0.98, 0.88, and 0.92, respectively), while this correlation was not observed in the midazolam-treated group. In the subgroup with sedation of less than 24 h, propofol provided a cost savings of approximately 2,000 pesetas (pts) per patient, due to shorter stays in the ICU. We conclude that propofol is a sedative agent with the same safety, higher clinical effectiveness, and a better cost-benefit ratio than midazolam in the continuous sedation of critically ill patients.

Aged↗

Combined small-cell and transitional cell carcinoma of the renal pelvis. A light microscopic, immunohistochemical, and ultrastructural study of a case with literature review.

Primary small-cell carcinomas of the kidney are rare, locally aggressive, and rapidly fatal neoplasms in elderly people. We report an example of combined small-cell and transitional cell carcinoma of the renal pelvis in a 71-year-old woman who had a history of heavy smoking. The cells that pertained to the small-cell component were morphologically mostly of an intermediate type. Immunohistochemically, they reacted with synaptophysin, carcinoembryonic antigen, and epithelial markers (Lu-5, EAB902, EAB903, and cytokeratin 19), and they contained scanty neurosecretory granules at the ultrastructural level. We review the literature on small-cell carcinoma of the kidney and renal pelvis, and we discuss the histogenesis of such a tumor.

Aged↗

Induction of apoptosis by wild-type p53 in a human colon tumor-derived cell line.

A wild-type p53 gene under control of the metallothionein MT-1 promoter was stably transfected into human colon tumor-derived cell line EB. Repeated inductions of the metallothionein wild-type p53 gene with zinc chloride results in progressive detachment of wild-type p53 cells grown on culture dishes. Examination at both the light and electron microscopic level revealed that cells expressing wild-type p53 developed morphological features of apoptosis. DNA from both attached and detached cells was degraded into a ladder of nucleosomal-sized fragments. Expression of wild-type p53 inhibited colony formation in soft agar and tumor formation in nude mice. Furthermore, established tumors in nude mice underwent regression if wild-type p53 expression was subsequently induced. Regressing tumors showed histological features of apoptosis. Thus, regression of these tumors was the result of apoptosis occurring in vivo. Apoptosis may be a normal part of the terminal differentiation program of colonic epithelial cells. Our results suggest that wild-type p53 could play a critical role in this process.

Base Sequence↗

Pharmacokinetics of alfuzosin after single oral administration to healthy volunteers, of three different doses.

The aim of this study was to assess the linearity of pharmacokinetic of alfuzosin, administered by oral route, at the doses of 1, 2.5, and 5 mg to 12 young healthy volunteers. The pharmacokinetic parameters (tmax, Cmax, AUC, t1/2 beta) obtained from plasma alfuzosin concentrations after administration of the three doses show that pharmacokinetics of alfuzosin is linear in the range of doses 1-5 mg. Mean pharmacokinetic parameters of alfuzosin observed after 1, 2.5, and 5 mg were, respectively: tmax (h) 1.5 +/- 0.3, 1.1 +/- 0.2, 1.3 +/- 0.1; Cmax (ng ml-1) 2.6 +/- 0.3, 9.4 +/- 1.2, 13.5 +/- 1.0; AUC (ng ml-1 h) 17.7 +/- 2.9, 51.7 +/- 7.1, 99.0 +/- 14.1; t1/2 (h) 3.7 +/- 0.4, 3.9 +/- 0.2, 3.8 +/- 0.3. Cmax (corrected by the dose) obtained after 2.5 mg was significantly higher than those obtained after 1 and 5 mg. This difference seems to be due principally to the intraindividual variability. The absence of statistically significant difference on individual values of AUC corrected by the administered dose, supports the linearity of the pharmacokinetics of alfuzosin in the range of doses between 1 and 5 mg. Some postural hypotension, clinical criterion, was observed with a frequency increasing with the dose in these healthy subjects: 0 volunteers of 12 after 1 mg, 3 volunteers of 12 after 2.5 mg and 4 volunteers of 12 after 5 mg.

Administration, Oral↗

Stability of K-ras mutations throughout the natural history of human colorectal cancer.

We have used a rapid, non-radioactive and sensitive method based on allele-specific amplification using the polymerase chain reaction for the identification of K-ras mutations in archival tissues of colorectal carcinomas. Our purpose was to determine whether or not K-ras mutation provides, when present, a tumour marker throughout the natural history of the disease. We have studied 35 patients who developed recurrent cancer. In 71% of these patients a ras mutation in codons 12 or 13 was observed in the primary tumour. For each of these cases an identical ras mutation was found in the DNA from the local or distant recurrence. In the 29% of cases where no ras mutation was observed in the primary tumour, no newly acquired ras mutation appeared in the recurrent tumour. The time interval between primary tumours and recurrences varied from 3 to 60 months. Our results indicate that K-ras mutation provides a stable tumour marker throughout the natural history of colorectal cancer.

Adenocarcinoma↗

Impaired response to recombinant hepatitis B vaccine in HIV-infected persons.

We studied the immunogenicity of the standard schedule of recombinant hepatitis B vaccine (20 micrograms per dose at months 0, 1, and 6) in 21 anti-human immunodeficiency virus (HIV)-positive persons. Relatively low titers of anti-HBs developed in only five subjects (23.8%) 1 month after the third dose; all five had T4 cell counts greater than 700 cells/mm and none of the 11 subjects with a T4 cell count below this value responded. Five of the 16 nonresponders to the vaccine later had acquired immunodeficiency syndrome (AIDS)-related complex (two) and AIDS (three), while none of the responders did. Our results show that anti-HIV-positive persons are poor responders to the recombinant hepatitis B vaccine, and that the absence of a response is an indicator of a more severe immune deficiency and of a poor prognosis. An optimal regimen of hepatitis B vaccination in HIV-infected persons is still to be established.

Follow-Up Studies↗

The dexamethasone suppression test as an adjunct in diagnosing depression.

Historically, affective disorders have been underdiagnosed among minorities, while schizophrenia is often overdiagnosed. Cultural differences in symptomatology, such as increased reports of auditory hallucinations, or language differences reportedly contribute to misdiagnoses in Hispanics. Consequently, we performed a thorough evaluation of Hispanic patients with a history of schizophrenia who remained diagnostic enigmas. Evaluation included the use of a Spanish-speaking interpreter, strict adherence to criteria of the Diagnostic and Statistical Manual of Mental Disorders, third edition (revised), and the dexamethasone suppression test. Five patients met criteria for major depression, and all but one were properly classified using the dexamethasone suppression test. Careful evaluation is needed with appropriate cultural and diagnostics support to avoid missing depression in Hispanics. The dexamethasone suppression test may be a useful adjunct in some difficult-to-diagnose patients.

Adult↗

Incidence of non-A, non-B hepatitis after screening blood donors for antibodies to hepatitis C virus and surrogate markers.

OBJECTIVE: To compare the effect of screening blood donors for antibodies to hepatitis C virus (anti-HCV) on the incidence of non-A, non-B hepatitis in recipients with that of screening blood donors for antibodies to hepatitis B core antigen (anti-HBc) and elevated alanine aminotransferase levels. DESIGN: Cohort analysis of serum samples from donors and recipients. Recipients were followed for 12 months to determine the occurrence of non-A, non-B hepatitis. SETTING: The blood-transmitted viruses unit and the liver unit of a university teaching hospital. SUBJECTS: A total of 250 patients who had open heart surgery and their 3142 blood donors. MEASUREMENTS: Donor sera were tested for anti-HCV by enzyme-linked immunosorbent assay (ELISA) and, in the event of a positive result, by recombinant immunoblot assay (RIBA). Antibodies to anti-HBc and serum alanine aminotransferase (ALT) levels were also measured. Measurements of anti-HCV and ALT activity in recipients were done before transfusion and at regular intervals during follow-up. MAIN RESULTS: Of the 250 transfusion recipients, 40 developed non-A, non-B hepatitis. Of the 3142 donors, 70 were positive for anti-HCV by ELISA, 440 were positive for anti-HBc, and 177 had alanine aminotransferase levels between 0.67 and 1.33 mukat/L. The sensitivity (87%), specificity (89%), positive predictive value (59%), and negative predictive value (97%) of blood-donor screening were higher for anti-HCV than for anti-HBc (82%, 36%, 21%, and 91%, respectively) and 70%, 29%, and 91%, respectively). The expected number of donors excluded because of the presence of anti-HCV was considerably smaller than that of donors with positive results for surrogate markers of hepatitis. CONCLUSION: Screening blood donors for the presence of anti-HCV is more accurate than screening for surrogate markers (anti-HBc and ALT) and protects more effectively against post-transfusion non-A, non-B hepatitis.

Alanine Transaminase↗

Alveolar soft-part sarcoma of the uterine corpus: histological, immunocytochemical and ultrastructural study of a case.

A case of alveolar soft-part sarcoma located in the uterine corpus is reported. It was an incidental finding in the hysterectomy specimen of a 40-year-old woman. Light and electron microscopic examination revealed periodic-acid-Schiff-positive, diastase-resistant, membrane-bound cytoplasmic granules and crystalloids. Tumour cells expressed immunoreactivity with vimentin, desmin, cytokeratins, NK1/C3 and HMB-45 antibodies. Four years postoperatively, the patient is still alive without evidence of disease. Differential diagnoses, immunocytochemistry and clinical management of uterine alveolar soft-part sarcoma are discussed and the literature reviewed.

Adult↗

Squamous cell carcinoma of the lung in a nonsmoking, nonirradiated patient with juvenile laryngotracheal papillomatosis. Evidence of human papillomavirus-11 DNA in both carcinoma and papillomas.

Malignant transformation of laryngeal juvenile papillomatosis most often occurs in patients with previous radiation therapy or smoking histories. We report the case of a 35-year-old, nonsmoking, nonirradiated man who developed squamous cell carcinoma of the lung with a 33-year history of laryngotracheal juvenile papillomatosis. Postmortem examination showed pulmonary cavitating papillomatosis and chest wall, vertebrae, and peribronchial lymph node involvement by tumor. Molecular studies (Southern blot, polymerase chain reaction) showed extrachromosomal human papillomavirus-11 (HPV11) DNA in both carcinoma and two laryngotracheal squamous cell papillomas, including one excised 20 years previously. Our observation is analogous to the previously reported cases of spontaneous (not related to irradiation or smoking) malignant transformation of juvenile laryngotracheal papillomatosis. Although HPV11 viral infection likely played a role in the malignant transformation, other less likely factors, such as drugs given for treatment and radiography performed throughout the illness, should be considered. Repeated pulmonary infections and the host immune response are additional considerations.

Adult↗

Hand and wrist strengthening exercises during rehabilitation of a patient with hereditary distal myopathy.

The effects of isometric and resistive strengthening exercises on myopathic distal muscles were examined by implementing a program of hand and wrist exercises during the rehabilitation of a patient with adult-onset hereditary distal myopathy. A 78-year-old man with this diagnosis for 18 years entered the hospital after a lumbar laminectomy and complete bedrest for seven weeks. After a three-week course of twice-daily Velcro board, therapeutic putty, and table-side isometric exercises, his hand and wrist manual muscle testing score, hand grasp and pinch strength, and nine-hole peg test times had all improved. In addition, the patient had moved from minimum-moderate assist in dressing and hygiene, and maximum assist in homemaking, to stand-by assist in both areas. The outcome demonstrates the feasibility and functional value of isometric and resistive strengthening exercises in muscles severely affected by a myopathic process.

Activities of Daily Living↗

Occurrence of Ki-ras and p53 mutations in primary colorectal tumors.

Twenty-four colorectal tumors and their paired mucosa were examined for allele loss on chromosomes 5 and 17, using polymerase chain reaction-amplified DNA, and for mutations in the Ki-ras and p53 genes. In addition, 19 benign polyps were analysed for mutations in the p53 gene. RFLP analysis of the long arm of chromosome 5 indicated an allele loss frequency of 47% for malignant tumors, a value somewhat higher than previously observed. Examination of the short arm of chromosome 17 indicated an allele loss of 60%. Sequence analysis of the p53 gene in colorectal tumors indicated that 64% contained a mutation. All tumors showing allele loss on chromosome 17 were mutant for p53, suggesting that mutation of one p53 allele precedes the hemizygotic loss of the wild-type allele. Sequence analysis of the p53 gene in 19 benign polyps, devoid of severe dysplasia, did not reveal any mutants, suggesting that the mutation of one p53 allele is an event that takes place after polyp formation. Ki-ras mutations were observed in 48% of the tumors examined. All tumors which were mutant for Ki-ras, except for one, were also mutant for p53.

Blotting, Northern↗

Negative symptoms: psychopathological models.

The psychopathological manifestations of schizophrenia have been broadly divided into positive and negative symptom groups. Even though there is no definitive consensus, psychomotor agitation, motor excitement, hallucinations, delusions and thought disorder constitute positive and psychomotor retardation, amotivation, apathy and decreased emotional expression are grouped into negative symptoms. The negative symptoms have been reported to appear late in the course of the illness and resistant to treatment with neuroleptics. While these claims have not been substantiated, the current interest on negative symptoms is related to the fact that many nonfunctioning institutionalized as well as ambulatory schizophrenics manifest negative symptoms. As chronic psychiatric beds have become scarce, many patients with negative symptoms who were harbored in the chronic mental hospitals have been released to the community care and some of these patients live on the streets. Thus their visibility has challenged psychiatry to focus its efforts on the etiology and treatment of negative symptoms.

Deinstitutionalization↗