Clozapine in refractory schizophrenia. Preliminary findings.
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Publications and source records attributed to J Costa.
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The novel tetraaza-macrocyclic compound 3,7,11-tris(carboxymethyl)-3,7,11,17-tetraaza-bicyclo[11.3.1]heptadeca-1(17),13,15-triene, abbreviated as ac3py14, was investigated for its activity against Mycobacterium tuberculosis and for induction of protective cellular immune responses. Perspective results show that ac3py14 and its Fe3+ 1:1 complex, [Fe(ac3py14)], inhibited radiometric growth of several strains of M. tuberculosis. Inhibition with 25 microg/mL varied from 99% for H37Rv to 80% and above for multiple drug-resistant clinical isolates. The capacity of ac3py14 to elicit a beneficial immune response without cellular apoptosis was assessed and compared to the effects of virulent M. tuberculosis. The present study produces evidence that after stimulation with ac3py14 there was significant production of interferon gamma (IFN-gamma), whereas the production of interleukin-5 (IL-5) remained low, and there was development of a memory population (CD45RO). The level of binding of Annexin V, a marker of apoptosis, was not sufficient to result in toxic effects toward alphabeta and gammadelta T cells and CD14+ macrophages. This preliminary study is the first report of a compound that simultaneously exerts an inhibitory effect against M. tuberculosis and induces factors associated with protective immune responses.
3,5-Dihydroxy-6,7,8-trimethoxyflavone, 3-O-methylquercetin, and helichrysetin were isolated from the flowers of the Rwandese medicinal plant, Helichrysum odoratissimum. Because of inconsistencies of the mp of the latter chalcone, a synthesis of helichrysetin was developed. 3-O-Methylquercetin was shown to be an active principle as it displayed antimicrobial activity.
BACKGROUND: After a short initial course of heparin therapy, patients with venous thrombo-embolism (VTE) require continuing anticoagulant therapy for several months after hospital discharge. At present, two small-scale studies have compared the efficacy and safety of low-molecular-weight heparin (LMWH) with warfarin in the secondary prevention of VTE. PATIENTS AND METHODS: We studied 654 consecutive patients, 202 with pulmonary embolism (PE) and 452 patients with deep vein thrombosis (DVT) of the lower limbs. 220/654 patients (34%) were considered to have some contraindications to coumarin, and were discharged on LMWH (dalteparin, Fragmin((R)), 10, 000 IU s.c. once daily). The remaining 434/654 patients were asked to choose between either coumarin or LMWH: 190 patients preferred LMWH and 244 coumarin. Patients were followed up for a 3-month (DVT patients) or 6-month (PE patients) period. RESULTS: 14/654 patients (2%) developed recurrent VTE while on anticoagulant therapy. One in every three recurrent episodes was PE (which was fatal in 2/5 patients), and half of the recurrent DVT were located in the contralateral leg. We failed to find any differences between patients receiving LMWH and those on coumarin therapy, but recurrences were more common in patients with cancer (hazard ratio: 17.15; 95% CI: 4.0-73.5; p < 0.001). 21 patients (3.3%) bled (major bleeding 5 patients; minor bleeding 16). Bleeding was more common in patients on coumarin therapy (hazard ratio: 3.14; 95% CI: 1.20-8.22; p = 0.02). CONCLUSIONS: Long-term LMWH therapy proved to be both effective and safe in the long-term treatment of VTE. Thus, we suggest long-term LMWH therapy should be considered for patients with contraindications to coumarin, or those with difficulties in coming to laboratory control.
A posttraumatic cerebellar hematoma in a 12-year-old boy is reported. It was observed by CT scan that the hematoma is discharged incompletely into the subdural space. The surgical treatment was successful with complete recovery. It is suggested that CT scan should be performed as soon as possible in cranial trauma with cerebellar signs.
OBJECTIVE: To evaluate the sensitivity and specificity of the carcinoembryonic antigen (CEA) immunoassay and Ki-ras genotyping as adjuncts to the cytologic diagnosis of pancreatic fine needle aspirates (FNAs). STUDY DESIGN: A retrospective study of 30 patients with pancreatic masses evaluated with CEA immunoassay and gel or hybridization analysis of allele-specific polymerase chain reaction for mutant Ki-ras (codons 12 and 13). DNA was isolated from fixed, paraffin-embedded samples. Diagnoses were correlated with cytologic evaluations and patient outcome. RESULTS: Diagnoses included 17 pancreatic carcinomas, 3 other malignancies and 10 benign lesions. Sixty-five percent of all FNAs had mutated Ki-ras, and 42% of samples with altered Ki-ras had multiple mutations. Replicate FNA samplings in five of six patients had concordant genotypes. Sensitivities for diagnosis were as follows: cytology alone, 76%; CEA alone, 82%; Ki-ras alone, 82%; cytology plus CEA, 100%; cytology plus Ki-ras, 94%. Although specificities for Ki-ras (30%) and CEA (50%) individually were low, elevated CEA level and mutated Ki-ras in a sample with negative cytology strongly indicated false negative cytology. CONCLUSION: The addition of either or both the CEA assay and Ki-ras mutation analysis enhances the sensitivity of the cytologic diagnosis of pancreatic carcinoma by FNA.
The purpose of the present study was to develop an optimal freezing method for cryopreservation of human donor corneas for transplantation. Three groups of ten human donor corneas each were cryopreserved using cooling rates of 0.5 degree C/ min, 1 degree C/min and 9 degrees C/min. The freezing medium contained 10% fetal calf serum and 7% dimethylsulphoxide. Ten additional human donor corneas were used as controls. Endothelial cell survival after complete thawing was assessed by calculating the mean endothelial cell density and percentage of non-viable endothelial cells from vital staining and scanning electron micrographs. Significant differences in endothelial cell survival between all groups were detected by analysis of variance (p < 0.001), but paired contrast found no real differences between corneas frozen at 0.5 degree C/min or 1 degree C/min. Nevertheless, 60% of the corneas cryopreserved at 1 degree C/min but only 10% of those cryopreserved at 0.5 degree C/min fulfilled both requirements to be considered suitable for transplantation (endothelial cell density > 2000 cells/mm2 and less than 10% dead cells). None of the corneas frozen at 9 degrees C/min fulfilled these requirements. Mean endothelial cell density of corneas frozen at 1 degree C/min was 2084 cells/mm2 (range 2020 to 2630 cells/mm2). Except for isolated corneas frozen at 0.5 degree C/min, only corneas cryopreserved at a cooling rate of 1 degree C/min achieved satisfactory endothelial cell survival for their use in transplantation. However the significant interindividual variability among corneas frozen at 1 degree C/min (ANOVA: p < 0.001) prevents prediction of the condition of the cornea after the complete cryopreservation process. Until this high variability can be drastically reduced, systematic corneal cryopreservation in eye banking remains unattainable.
Triatoma brasiliensis is one of the most important vectors of Chagas disease in the semiarid zone of the northeast of Brazil. Intraspecific morphological and behavioural variation has been reported for different populations. Results for four distinct populations using eight isoenzymes are reported here. The literature describes three subspecies: T. brasiliensis brasiliensis Neiva, 1911; T. brasiliensis melanica Neiva & Lent, 1941 and T. brasiliensis macromelasoma Galvão, 1956. These subspecies differ mainly in their cuticle colour pattern and were regarded as synonyms by Lent and Wygodzinsky (1979). In order to evaluate whether the chromatic pattern is a morphological variation of different melanic forms within T. brasiliensis or due to interspecific variation, field collections were performed in localities where these three subspecies have been described: Caicó (Rio Grande do Norte), the type-locality for T. b. brasiliensis; Petrolina (Pernambuco) for T. b. macromelasoma and Espinosa (Minas Gerais) for T. b. melanica. A fourth distinct chromatic pattern was found in Juazeiro (Bahia). A total of nine loci were studied. Values of Nei's genetic distance (D) were calculated. T. b. brasiliensis and T. b. macromelasoma are the closest populations with a D = 0.295. T. b. melanica had a D > or = 0.537 when compared to the others, a distance in the range of interspecific variation for other triatomine species.
Triatoma brasiliensis is considered as one of the most important Chagas disease vectors in the northeastern Brazil. This species presents chromatic variations which led to descriptions of subspecies, synonymized by Lent and Wygodzinsky (1979). In order to broaden bionomic knowledge of these distinct colour patterns of T. brasiliensis, captures were performed at different sites, where the chromatic patterns were described: Caicó, Rio Grande do Norte (T. brasiliensis brasiliensis Neiva, 1911), it will be called the "brasiliensis population"; Espinosa, Minas Gerais (T. brasiliensis melanica Neiva & Lent 1941), the "melanica population" and Petrolina, Pernambuco (T. brasiliensis macromelasoma, Galvão 1956), the "macromelasoma population". A fourth chromatic pattern was collected in Juazeiro, Bahia the darker one in overall cuticle coloration, the "Juazeiro population". At the sites of Caicó, Petrolina and Juazeiro, specimens were captured in peridomiciliar ecotopes and in wilderness. In Espinosa the specimens were collected only in wilderness, even though several exhaustive captures have been performed in peridomicile at different sites of this municipality. A total of 298 specimens were captured. The average registered infection rate was 15% for "brasiliensis population" and of 6.6% for "melanica population". Specimens of "macromelasoma" and of "Juazeiro populations" did not present natural infection. Concerning trophic resources, evaluated by the precipitin test, feeding eclecticism for the different colour patterns studied was observed, with dominance of goat blood in household surroundings as well as in wilderness.
This paper is a review of the current situation of the treatment of human African trypanosomiasis. The existing approved drugs are old, toxic and/or expensive. Therapeutic failures are common. Several factors may contribute to the problems of chemotherapy, including differences in the epidemiology of the disease, difficulties in the diagnosis and staging of the infection, availability, distribution and pharmacologic properties of drugs, standardization of treatment regimens, response to therapy, follow-up period, and relapses and clinical trials. The new therapeutic approaches include the development and approval of new drugs, the use of new therapeutic regimens, the study of drug combinations, and the development of new formulations.
This study presents a list of 34 Anoplura type specimens deposited in the Werneck Collection of Instituto Oswaldo Cruz, Rio de Janeiro, RJ, Brazil. It includes 18 holotypes, 16 allotypes, 88 paratypes and 10 neotypes, distributed among the genera: Enderleinellus, Fahrenholzia, Haematopinus, Hoplopleura, Linognathus, Microthoracius, Pecaroecus, Polyplax and Pterophthirus. The types are related according to their respective data and literature.
The presence of Triatoma rubrovaria in Brazil has only been confirmed in the States of Paraná and Rio Grande do Sul (RS), where it is found naturally infected with Trypanosoma cruzi. In the wild environment it occurs in rocky habitats and has an eclectic diet, feeding from cockroaches, reptiles and mammals. Data from the Chagas Disease Control Program obtained by the Fundação Nacional de Saúde, between 1975 and 1997, indicate a growing domiciliary and peridomiciliary invasion of T. rubrovaria in RS, where it has become the most frequently Triatominae species captured in this state since the control of Triatoma infestans. In order to monitor this process, we analyzed collection data derived from 22 years of control campaigns against T. infestans. Collection data for triatomines from domestic habitats show an inverse relationship, with high numbers of T. infestans and low numbers of T. rubrovaria during 1976-1987, compared to the following ten years, 1986-1997, when the number of T. infestans dropped drastically and that of T. rubrovaria increased. There are no consistent indications of intradomiciliary colonization by T. rubrovaria, since only low numbers of nymphs have been captured in the intradomiciliary ecotopes. Nevertheless, this species appears to have preadaptive characteristics for anthropic ecotopes, and should be kept under constant epidemiological surveillance.
We describe previously unreported intranuclear inclusions in 2 cases of malignant fibrous histiocytoma. The inclusions were found in 2-10% of the tumor cells removed from the patients and in 2-10% of the cells examined in tumor tissue xenotransplanted in nude mice. By stereo electron microscopy the inclusions are closely packed undulating fibrils 18-23 nm in diameter. They are sometimes associated with fibrillary bodies. They closely resemble the inclusions reported in some animals inoculated with serum from patients with non-A non-B hepatitis; however, their nature at present is unknown.
Although much has been written about psychodrama as a therapeutic and educational method with patients, there is little evidence of its effectiveness as an activity for professional clinicians. The authors describe how the basic elements, phases and techniques of psychodrama have been used with groups of health workers to improve their clinical performance and personal life. The therapy has important applications in helping staff come to terms with the emotional stresses of their work with patients.
INTRODUCTION: The pseudotumor cerebri syndrome (PTC) is a clinical entity of unknown etiology affecting mainly young, obese women. The major morbidity factor in this condition is the possibility of vision loss, initially considered to be low, but now known to affect a significant proportion of patients. CLINICAL CASE: We describe a case of PTC in a young, obese black women who presented with headache, transient visual blurring and diplopia. Besides obesity, there where no other relevant clinical findings, namely other pathologies and history of medication use. An extensive analytical workup was negative and the CSF showed no abnormalities, aside from increased pressure. Brain MRI was also normal. The clinical course was progressively worse, consisting of rapid vision loss associated with an intracranial pressure of over 850 mmH2O, despite treatment with diuretics (acetazolamide, furosemide and spironolactone) in therapeutic dosage. Eventually, the patient needed the rapid implantation of a lumboperitoneal shunt to prevent blindness, and went on to make a nearly full recovery. CONCLUSIONS: In all major series of PTC, loss of vision has been reported to occur in a significant percentage of patients, and cases have been described in which a catastrophic course with rapid progression to near blindness has led to the introduction of the designation of 'malignant' pseudotumor cerebri. We believe that such cases, although rare, need to be recognized as the malignant end of the spectrum of PTC, and that their management constitutes a neurological emergency.
Tissue microarrays are a method of harvesting small disks of tissue from a range of standard histologic sections and placing them in an array on a recipient paraffin block such that hundreds of cases can be analyzed simultaneously. This technique allows maximization of tissue resources by analysis of small-core biop sies of blocks, rather than complete sections. Using this technology, a carefully planned array can be constructed with cases from pathology tissue block archives, such that a 20-year survival analysis can be performed on a cohort of 600 or more patients by use of only a few microliters of antibody in a single experiment. The reflex criticism of this technique is that the tissue analyzed is not representative, especially in antigens with heterogeneous staining patterns. This review addresses this issue, as well as the issue of antigen preservation or durability, which validates construction of arrays from archives. Strategies and methods of construction and analysis of the arrays are discussed, as well as some other unusual array applications. This technique can provide a highly efficient, high-throughput mechanism for evaluation of protein expression in large cohorts. It has the potential to allow validation of new genes at a speed comparable to the rapid rate of gene discovery afforded by DNA microarrays.
Tricyclic antidepressant overdose is a frequent diagnosis in the emergency room. It is responsible for a significant percentage of hospital admissions for observation and treatment. This is due to its cardiac (as well as neurologic) toxicity, and the difficulty in predicting its clinical gravity. The authors present this paper with two objectives in mind: 1) information about a common and significant cardiological emergency; 2) presentation of the methodology concerning systematic reviews of the literature. In this second (of four) articles, the clinical presentation and diagnosis of tricyclic antidepressant overdose are presented (in the first article--published in the previous issue of the Journal--we discussed the epidemiological aspects). In the remaining two papers we will present its management, prognosis and prevention. NOTE: This is the second of a series of four articles on the cardiac toxicity of tricyclic antidepressant overdose; the next two articles will be presented in the September and October issues of the Revista.
In recent years molecular biology has been applied to the study of colonic carcinoma, both in the human and in the experimental animal. The data obtained have enriched our understanding of colonic carcinogenesis and are of potential interest for cancer diagnosis and prevention. In this paper we review part of the available literature on the molecular characterisation of colon tumors, with emphasis on the issues of clonality, in vitro cell lines, tumor progression and heredity of colon cancer.