The protective action of chlorpromazine on the spinal cord of rabbits submitted to ischemia and reperfusion is dose-dependent.

BACKGROUND: Chlorpromazine (CPZ), at high doses, has been shown to protect the central nervous system in experimental models of ischemia and reperfusion. The purpose of this study was: 1) to investigate the protection afforded by different doses of CPZ on the spinal cord of rabbits submitted to ischemia and reperfusion. 2) to correlate the motor impairment of the hind limbs and the percentage of damaged neurons in the anterior horns of the lumbar spinal cord in treated and untreated animals. METHODS: Seventy-two New Zealand white rabbits were divided into 6 equal groups (n=12): sham operation, control and 4 study groups. Spinal cord ischemia was obtained by clamping the abdominal aorta caudally to the renal arteries for 30 min, after which it was released and the animals were observed for a period of 48 hrs. The control animals received 3 ml/kg of 0.9% NaCl, i.v., 10 min before aorta clamping. The experimental animals received CPZ, i.v., at doses of 2, 1 and 0.5 mg/kg, 10 min before aorta clamping. In one group 1 mg/kg of CPZ was given 10 min before aorta clamping and the same dose was repeated 2 hrs after the beginning of reperfusion. The spinal cord of the control animals and of those who received one CPZ dose of 2 mg/kg was processed for light microscopy examination. RESULTS: Motor scores of the hind limbs, graded 0 to 4, obtained 48 hrs after the beginning of reperfusion showed that CPZ was effective at doses of 2 and 1 mg/kg. No significant difference was observed with the dose of 0.5 mg/kg. However, the best results were obtained with the dose of 2 mg/kg administered in a fractionated manner. Histological examination revealed that at the dose of 2 mg/kg, CPZ protected a significant number of neuronal cells and that motor recovery hardly occurred when the number of damaged neurons exceeded 50%. CONCLUSIONS: 1) The neuroprotective action of CPZ is dose-dependent in the ischemic spinal cord of rabbits. The lower protective dose is 1 mg/kg, which is too high for human beings. 2) There is an inverse correlation between motor recovery and percentage of damaged neurons, and the critical point seems to be between 30% and 50%.

Distinct nonrandom patterns of chromosomal deletions in giant-cell lesions of bone

Cytogenetic analyses were performed on a bone giant cell reparative granuloma (GCRG) and on three bone giant cell tumors (GCT). The present GCRG case is the second to be described cytogenetically. A modal chromosome number of 46 was observed in all samples. Clonal chromosome abnormalities were detected in all cases. The numerical alterations most frequently observed involved the loss of chromosomes 17 and 18. Among the structural anomalies observed, there was preferential involvement of chromosomes 6 and 10. Three GCT cases presented del(10)(p13) and two cases presented del(6)(q25) (1 GCRG and 1 GCT). These breakpoints mapped on 10p and 6q may harbour genes of importance in the development of bone giant cell tumors

Cytogenetic description of breast fibroadenomas: alterations related solely to proliferation?

Twelve breast fibroadenomas were analyzed cytogenetically and only four were found to have clonal alterations. The presence of chromosomal alterations in fibroadenomas must be the consequence of the proliferating process and must not be related to the etiology of this type of lesion. In contrast, the few fibroadenomas that exhibit chromosomal alterations are likely to be those presenting a risk of neoplastic transformation. Clonal numerical alterations involved chromosomes 8, 18, 19, and 21. Of the chromosomal alterations found in the present study, only monosomy of chromosomes 19 and 21 has been reported in breast fibroadenomas. The loss of chromosome 21 was the most frequent alteration found in our sample. The study of benign proliferations and their comparison with chromosome alterations in their malignant counterparts ought to result in a better understanding of the genes acting on cell proliferation alone, and of the genes that cause these cells to exhibit varied behaviors such as recurrences, spontaneous regression and fast growth

Cytogenetic description of breast fibroadenomas: alterations related solely to proliferation?

Twelve breast fibroadenomas were analyzed cytogenetically and only four were found to have clonal alterations. The presence of chromosomal alterations in fibroadenomas must be the consequence of the proliferating process and must not be related to the etiology of this type of lesion. In contrast, the few fibroadenomas that exhibit chromosomal alterations are likely to be those presenting a risk of neoplastic transformation. Clonal numerical alterations involved chromosomes 8, 18, 19, and 21. Of the chromosomal alterations found in the present study, only monosomy of chromosomes 19 and 21 has been reported in breast fibroadenomas. The loss of chromosome 21 was the most frequent alteration found in our sample. The study of benign proliferations and their comparison with chromosome alterations in their malignant counterparts ought to result in a better understanding of the genes acting on cell proliferation alone, and of the genes that cause these cells to exhibit varied behaviors such as recurrences, spontaneous regression and fast growth.

Comparative genomic hybridization detects novel amplifications in fibroadenomas of the breast.

Comparative genomic hybridization analysis was performed for identification of chromosomal imbalances in 23 samples of fibroadenomas of the breast. Chromosomal gains rather than losses were a feature of these lesions. Only two cases with a familial and/or previous history of breast lesions had gain of 1q or 16q as the sole abnormality. The most frequently overrepresented segments were 5p14 (10/23 cases), 5q34-qter (6/23 cases), 13q32-qter (6/23 cases), 10q25-qter (5/23 cases), and 18q22 (4/23 cases). Some of these regions have previously been associated with breast carcinoma, but this study indicates that gain of these regions can also occur in benign breast lesions. Our findings may provide a basis for conducting further investigations to locate and identify genes associated with proliferation that may be involved in the early steps of tumorigenesis of the breast.

Karyotypic and histopathologic findings in an accessory breast.

Accessory breasts are a clearly hereditary anomaly. They enlarge during pregnancy and lactation as a consequence of high blood levels of estrogen and prolactin, and are subject to all the diseases that occur in normal breasts. Cytogenetic analysis was performed on one accessory breast. The monossomy of chromosome 16 was the main alteration found in this material. Nonscheduled cell proliferations may produce chromosome alterations, most of them with no clinical meaning. When relevant genes are altered, major proliferations or progression to malignancy may occur.

Hemangioendothelioma of bone in a patient with a constitutional supernumerary marker.

A 13-year old girl was diagnosed as having a bone hemangioendothelioma. Cytogenetic studies identified the presence of a small supernumerary marker chromosome in this patient. Classical cytogenetic methods using G-, C-, Ag-NOR-banding were supplemented by spectral karyotyping (SKY) and fluorescence in situ hybridization to reveal a karyotype 47,XX,+mar.ish der(22)(D22S543+) karyotype in cells derived from the tumor and lymphocytes. These findings suggest that the supernumerary marker chromosome originated from the proximal centromeric region of chromosome 22, and that trisomy of the region 22q11 was not associated with adverse phenotypic effects, but that the presence of trisomy 22q11 may be related to the development of this tumor.

Pathological and karyotypic abnormalities in advanced gastric carcinomas.

Twenty samples of stomach cancers were analyzed by conventional cytogenetic and histopathological techniques. Nineteen tumors were diagnosed as adenocarcinomas and one as an adenosquamous carcinoma. Multiple and complex chromosomal abnormalities were found in the cases evaluated cytogenetically. This heterogeneity of chromosomal changes appears to indicate a certain correlation with tumor progression. Histological analysis showed a distinctive growth pattern of gastric cancer samples and a potential for invasiveness and recurrence for all tumors as well as a poor prognosis.

Primary intracranial germ cell tumors without an isochromosome 12p.

Primary intracranial germ cell tumors are the result of the transformation of primordial cells that are unable to migrate to their normal place. These tumors are rare, accounting for less than 5% of all intracranial tumors and less than 3% of childhood neoplasias. In this paper, we have studied cytogenetically two primary intracranial germ cell tumors, a pineal region germinoma, and a mature teratoma in the right lateral ventricle. Neither tumor presented polyploidy or isochromosome 12p, considered to be characteristic of gonadal germ cell tumors. In the five reports in the literature, only one intracranial germ cell tumor presented i(12p). Perhaps i(12p) negative cases characterize a subtype of germ cell tumors.

Analgesic effect of subarachnoid neostigmine in two patients with cancer pain.

Two patients suffering with severe pain due to metastatic abdominal neoplasm were selected to examine whether subarachnoid neostigmine provided effective pain relief. Neostigmine was injected through a catheter introduced into the subarachnoid space at L4-L5. Patients were monitored for changes in arterial blood pressure, cardiac and respiratory rates, body temperature, level of consciousness and neurologic change. Pain was classified by the patients on a verbal four-grade scale, and analgesia was classified on a verbal three-grade scale. Complete pain relief was obtained 2 h after neostigmine (0.2 mg) in one patient and 4 h after neostigmine (0.1 mg) in the second patient. Pain of mild intensity returned 20 and 22 h after drug administration, respectively. Gastrointestinal discomfort was observed in both cases, but nausea and vomiting occurred only in the patient treated with the highest dose of neostigmine. No significant change in the monitored parameters was observed, except for a 6-h period of decreased blood pressure in the patient treated with the lower dose of neostigmine which required no specific treatment. The results obtained in these anecdotal cases indicate that subarachnoid neostigmine may provide analgesia in patients with pain arising from neoplasia, but further studies using controlled trials are needed before the drug is brought into clinical use.

Chromosomes in the genesis and progression of ependymomas.

Cytogenetic analysis was performed on cultures of primary ependymal tumors with different degrees of malignancy (I-IV) obtained from four patients, none of whom had received therapy before karyotypic evaluation. The most common abnormalities were monosomy 17 and 22 in four cases and losses of sex chromosomes in three cases. Structural rearrangements of chromosome 2 were a finding for all cases and involved loss of material at 2q32-34. Other structural chromosome abnormalities detected involved chromosomes 4, 6, 10, 11, 12, and X. We also reviewed data on 22 cases previously reported.

Liver injury and generation of hydroxyl free radicals in experimental secondary hemochromatosis.

An experimental model of secondary hemochromatosis is described. Saccharated iron was administered i.v. to rats for 7 months in total doses in the range 1.0-1.7 g per kg body weight. After the completion of iron loading, the biochemical measurements revealed elevation of alanine aminotransferase (ALT), slight reduction of plasma glucose concentration, and significant reduction of both plasma and liver ascorbic-acid levels. The mean liver iron concentration was 50 times higher in iron-loaded animals than in controls. High concentrations of inorganic iron were also observed in spleen, pancreas, and heart. Histologic analysis revealed marked hepatic fibrosis in most animals in the experimental group. These results demonstrate this animal model presents some pathologic findings observed in human transfusional hemochromatosis. Additionally, hydroxyl free radicals were detected by electron paramagnetic resonance (EPR) spectroscopy in the iron-overloaded liver tissue processed at pH 5.0. No free radicals were detected at pH 7.4. These results suggest the possible participation of hydroxyl free radicals in the cellular toxicity of iron overload.

Cytogenetic study of a pineocytoma.

The cytogenetic findings based on G-banding in a pineocytoma detected in a 29-year-old woman are reported. The chromosomal study showed numerical alterations involving chromosomes X, 5, 8, 11, 14, and 22, structural alterations of chromosomes 1, 3, 12, and 22, as well as various markers. Tumors of the pineal region are infrequent, and this is the first report of a pineocytoma studied cytogenetically.

The effect of proximal gastric vagotomy plus duodenoplasty on duodenogastric reflux.

Alkaline reflux gastritis is a clinical syndrome that results from a mucosal injury by duodenal contents. In this study, the amount of duodenogastric reflux was assessed in patients who previously underwent proximal gastric vagotomy (PGV group; n = 11) and PGV plus duodenoplasty (PGV+D group; n = 10) as a treatment for duodenal ulcer. The control group (A) consisted of 11 healthy volunteers without endoscopic abnormalities. A quantitative index of duodenogastric reflux was obtained in each case by determining the percentage of the injected dose of 99mTechnetium-DISIDA that was recovered by continuous aspiration of gastric juice in fasting subjects. In the PGV group, the percentage of administered 99mTechnetium-DISIDA recovered from the stomach (median: 0.69%; range: 0.09%-3.61%) did not differ significantly (P > 0.05) from that of the PGV+D group (median: 0.49%; range: 0.09%-3.91%) and from that of the A group (median: 1.47%; range: 0.22%-3.01%). The results show that proximal gastric vagotomy plus duodenoplasty did not increase duodenogastric reflux.

[Tissue levels of 6-ketoprostaglandin Fl alpha and integrity of gastric mucosa in patients with Chagas disease]. / Níveis teciduais da prostaglandina 6-ceto-PGF 1 alpha e integridade da mucosa gástrica em pacientes com doença de Chagas.

An increased prevalence of chronic gastritis has been reported in patients with chronic Chagas' disease (American trypanosomiasis), which is regarded to be model of intrinsic denervation of the gastrointestinal tract. In order to investigate whether this condition is associated with a reduction of prostaglandin levels in gastric mucosa, we studied 14 Chagas' disease patients with megaesophagus and/or megacolon and compared them with 10 control subjects. All patients and controls underwent an upper gastrointestinal tract endoscopy where biopsies were collected from the antrum for histology and for 6-keto-PGF 1 alpha radioimmunoassay. In the Chagas' disease group, the proportion of patients with either moderate or severe gastritis (7/14) was significantly higher (p < 0.01) than in the control group (0/10). Values for antral 6-keto-PGF 1 alpha in Chagas' disease patients (median: 80.75 ng/g; range 36.5-245.6 ng/g) were slightly lower than those obtained in controls (median: 116.2 ng/g; range: 13.1-269 ng/g), but the difference was not statistically significant (p > 0.10). These results confirm previous observations suggestive of an increased prevalence of chronic gastritis in Chagas' disease, but do not support the view that chronic destruction of the intramural neurons of the gut, which is known to occur in this condition, is associated with a reduction of prostaglandin levels in gastric antral mucosa.

[Cryptococcus meningitis: clinical course, development and histopathologic aspects depending on the predisposing factors]. / Meningite criptocócica: aspectos clínicos, evolutivos e histopatológicos segundo a condição predisponente.

Seventeen consecutive cases of cryptococcal meningitis diagnosed at Hospital das Clínicas of Ribeirão Preto Medical School (São Paulo State Brazil) between 1969 and 1985 were reviewed. For analysis the patients were separated in 3 groups: I. three patients without immunodeficiency; II. six patients with associated disease: cancer (3), diabetes (2) and alcoholism (1); III. Eight renal transplant recipients that developed cryptococcosis after 18 to 67 months of immunosupression with steroids and azathioprine. The median interval between onset of symptoms and diagnosis of infection was greater in Group II (53 days) than in Groups I (25 days) or III (28 days). Neck stiffness, cranial nerve involvement and papilledema were more frequent in Group I than in Group II or III, but fever and focal neurological signs were observed only in patients of two last groups. Cerebrospinal fluid examination showed a mild lymphocytic pleocytosis in most patients, but transplant cases had polymorphonuclear cells more frequently. Late mortality was higher in patients with underlying disease and the prognosis was better for transplant patients that received effective antifungal therapy. Besides cryptococci, autopsy findings in 8 cases revealed granuloma formation in tissues, except in patients of Group II (2 cases). The differences between the groups suggest that clinical characteristics, evolution and postmortem findings of the cryptococcal meningitis are changed according to type of immunodeficiency presented by the patient.

Karyotypic evolution of human meningioma. Progression through malignancy.

Cytogenetic analysis of an untreated sarcomatous meningioma from a patient submitted to two surgeries separated by 1 year are reported. The material from the first surgery was mostly hypodiploid, with a modal chromosome number of 42. Alterations of chromosome 22 were found in 80.6% of the cells. Four chromosome markers were found involving chromosomes 1, 2, 6, and 22, and numerical alterations involving chromosomes 8, 9, 10, 13, 14, 15, 18, 19, 20, 21, and Y. Although the modal chromosome number of the material from the second surgery was 45 (17.9% of the cells), 43.1% of its cells were hyperdiploid, 73% of these being in the triploid-tetraploid range. Dicentric and ring chromosomes were very frequent. Alterations involving chromosome 22 were still present. There was a recurrent trisomy of chromosome 3. To our knowledge, this is the first cytogenetic description, with banding techniques, of a malignant meningioma.

[Endoscopic evaluation of the involvement of the esophagus, stomach and duodenum in human paracoccidioidomycosis]. / Avaliação endoscópica do comprometimento de esôfago, estômago e duodeno na paracoccidioidomicose humana.

The upper gastrointestinal tract was investigated endoscopically in 30 patients with paracoccidioidomycosis. Esophagus, stomach and duodenum showed, respectivelly, 40%, 53% and 43% of endoscopic alterations. The histopathological examination of biopsy tissue revealed no specific lesions in esophagus and stomach, but P. brasiliensis was observed in three cases of duodenal lesions: two cases with mucosal diffuse erosions and one case of duodenal polyp. It is concluded that duodenal paracoccidioidomycosis is not rare and could be revealed by endoscopic examination in patients with disseminated disease.