Antioxidant defence of the neonatal rat brain against acute hyperammonemia

Oxidative stress associated with the presence of elevated concentrations of ammonia in the brain has been proposed as one possible mechanism involved in ammonia toxicity. In a previous study [Brain Res.973 (2003) 31], we reported that neonatal rats are more resistant to acute ammonia toxicity than adult rats. In the present work, we studied the antioxidant status of the brain in hyperammonemic neonatal rats. Increased activities of the antioxidant enzymes and enhanced glutathione content were found in the brains of the hyperammonemic neonatal rats as compared to the controls. In addition, no changes in brain reactive oxygen species (ROS) levels and lipid peroxidation due to hyperammonemia were found. Therefore, acute ammonia intoxication does not induce oxidative stress in neonatal rats, a fact that may explain the resistance against hyperammonemia shown by neonatal rats.     

Phase II trial of sequential high-dose chemotherapy with paclitaxel,melphalan and cyclophosphamide,thiotepa and carboplatin with peripheral blood progenitor support in women with responding metastatic breast cancer

A single high-dose cycle of chemotherapy can produce response rates in excess of 50%. However, disease-free survival (DFS) is 15-20% at 5 years. The single most important predictor of prolonged DFS is achieving a complete response (CR). Increasing the proportion of patients who achieve a complete response may improve disease-free survival. Women with metastatic breast cancer and at least a partial response (PR) to induction chemotherapy received three separate high-dose cycles of chemotherapy with peripheral blood progenitor support and G-CSF. The first intensification was paclitaxel (825 mg/m(2)), the second melphalan (180 mg/m(2)) and the third consisted of cyclophosphamide 6000 mg/m(2) (1500 mg/m(2)/day x 4), thiotepa 500 mg/m(2) (125 mg/m(2)/day x 4) and carboplatin 800 mg/m(2) (200 mg/m(2)/day x 4) (CTCb). Sixty-one women were enrolled and 60 completed all three cycles. Following the paclitaxel infusion most patients developed a reversible, predominantly sensory polyneuropathy. Of the 30 patients with measurable disease, 12 converted to CR, nine converted to a PR*, and five had a further PR, giving an overall response rate of 87%. The toxic death rate was 5%. No patient progressed on study. Thirty percent are progression-free with a median follow-up of 31 months (range 1-43 months) and overall survival is 61%. Three sequential high-dose cycles of chemotherapy are feasible and resulted in a high response rate. The challenge continues to be maintenance of response and provides the opportunity to evaluate strategies for eliminating minimal residual disease.     

Phylogenetic analysis of the genus Plasmodium based on the gene encoding adenylosuccinate lyase.

Phylogenetic studies of the genus Plasmodium have been performed using sequences of the nuclear, mitochondrial and plastid genes. Here we have analyzed the adenylosuccinate lyase (ASL) gene, which encodes an enzyme involved in the salvage of host purines needed by malaria parasites for DNA synthesis. The ASL gene is present in several eukaryotic as well as prokaryotic organisms and does not have repeat regions, which facilitates the accuracy of the alignment. Furthermore, it has been shown that ASL is not subject to positive natural selection. We have sequenced the ASL gene of several different Plasmodium species infecting humans, rodents, monkeys and birds and used the obtained sequences along with the previously known P. falciparum ASL sequence, for structural and phylogenetic analysis of the genus Plasmodium. The genetic divergence of ASL is comparable with that observed in other nuclear genes such as cysteine proteinase, although ASL cannot be considered conserved when compared to aldolase or superoxide dismutase, which exhibit a slower rate of evolution. Nevertheless, a protein like ASL has a rate of evolution that provides enough information for elucidating evolutionary relationships. We modeled 3D structures of the ASL protein based on sequences used in the phylogenetic analysis and obtained a consistent structure for four different species despite the divergence observed. Such models would facilitate alignment in further studies with a greater number of plasmodial species or other Apicomplexa.     

Germ cell tumors of the CNS in children: recent advances in therapy

Primary germ cell tumors of the central nervous system are rare neoplasms, accounting for no more than 2% of all malignancies in children and young people under 20 in the Western hemisphere. They have unique features related to age at diagnosis and sites of origin, as well as race and gender predilection. Prognosis has been clearly shown to be strongly related to pathological classification as either pure germinoma or nongerminomatous germ cell tumor, although many of these lesions are comprised of mixed elements. The presence of serum or cerebrospinal fluid tumor marker elevation has been an essential determinant of response to treatment. Because of the deleterious effects of irradiation on the immature nervous system, investigators have used chemotherapeutic strategies that either reduce or eliminate radiation therapy. In this article, we review the most recent advances in therapy for CNS germ cell tumors in the pediatric population and highlight the importance of cooperative trials in this setting. Received: 12 April 1999     

Fat-Free Mass Depletion and Inflammation in Patients with Bronchiectasis

Fat-free mass depletion has been related to increased inflammatory activity and to increased morbidity and mortality in chronic respiratory diseases. The aims of our study were to determine the nutritional status and serum levels of adipocytokines and inflammatory cytokines in patients with bronchiectasis of any etiology and their relation with respiratory parameters. A cross-sectional study was designed that included patients aged >14 years with diagnostic criteria for bronchiectasis. Anthropometric parameters; a diet questionnaire; hand grip dynamometry; levels of leptin, adiponectin, interleukin-6 (IL-6), tumor necrosis factor-α, and ultrasensitive C-reactive protein; as well as respiratory parameters (ie, clinical, radiologic, and spirometric values) were assessed. Ninety-three clinically stable patients were recruited, 43 with cystic fibrosis, 31 with noncystic fibrosis bronchiectasis, and 19 with cystic fibrosis transmembrane conductance regulator-related bronchiectasis. Fat-free mass depletion was present in 31% of patients, with no differences according to the etiology of the bronchiectasis. Correlations were found between inflammatory cytokines (ie, IL-6) and exacerbations, bronchorrea, forced expiratory volume in 1 second, and Bhalla score. Patients with worse respiratory disease severity, malnutrition, and diabetes had significantly higher levels of IL-6. Adiponectin correlated significantly and positively with fat mass and fat mass index and negatively with fat-free mass, fat-free mass index, and hand dynamometry. Leptin correlated positively with body mass index, fat mass and fat mass index, and negatively with fat-free mass, fat-free mass index, and dynamometry. Patients with bronchiectasis present a high percentage of fat-free mass depletion, independent of the etiology of the disease. The levels of inflammatory cytokines (especially IL-6) may be useful markers of disease severity. Adiponectin levels were higher in patients with fat-free mass depletion.     

Depression and anxiety symptoms in bronchiectasis: associations with health-related quality of life

Background and purpose

Bronchiectasis causes pulmonary infections and loss of lung function, resulting in chronic respiratory symptoms and worsening health-related quality of life. The aims of this study were to measure symptoms of depression and anxiety in a sample of patients with bronchiectasis and evaluate their relationship to health outcomes and health-related quality of life.

Methods

This cross-sectional study included adolescents and adults with bronchiectasis. Patients completed the hospital anxiety and depression scale and the St. George respiratory questionnaire. Health outcome data, including clinical, radiological and spirometric values, were recorded from medical charts.

Results

Ninety-three participants with bronchiectasis of any aetiology were recruited: 20 % had elevated depression-related scores and 38 % had elevated anxiety-related scores. Increased symptoms of depression and anxiety were significantly associated with age; anxiety was associated with more frequent exacerbations. Regression analyses indicated that after controlling for demographic (gender and age) and clinical variables (exacerbations frequency, daily sputum, aetiology and spirometry), both depression and anxiety symptoms predicted significantly worse health-related quality of life. In comparison with other predictors, psychological symptoms explained the largest amount of variance in health-related quality of life.

Conclusions

Symptoms of depression and anxiety were significant predictors of health-related quality of life in patients with bronchiectasis, independently of respiratory involvement, gender, age or other variables.     

Heterotopic pregnancy associated with gamete intra-fallopian transfer.

Recent reports in the literature have focused on the increased risk of heterotopic pregnancy after the transfer of multiple concepti or oocytes. In an international collaborative patient registry between 1985 and 1989, 601 clinical pregnancies resulted from 2092 gamete intra-Fallopian transfer (GIFT) retrieval cycles. Five of the pregnancies were heterotopic (0.83%). After surgical intervention, all five cases of combined gestation resulted in live birth from intrauterine pregnancies. Routine vaginal ultrasonographic examination of the adnexa in patients who conceive after GIFT may help early diagnosis of heterotopic pregnancy. If the diagnosis is made early, conservative treatment may preserve the future fecundity of the patient and more intrauterine pregnancies may be salvaged.     

Leptomeningeal tumor in primarchy central nervous system lymphoma: Recognition,significance, and implications

The true incidence of leptomeningeal tumor in priMarchy central nervous system lymphoma is unknown. We studied prospectively the cerebrospinal fluid profile of 96 patients without acquired immunodeficiency syndrome but with priMarchy central nervous system lymphoma at diagnosis, at completion of treatment, and at recurrence. Magnetic resonance images and pathology slides were examined for evidence of leptomeningeal tumor. Leptomeningeal tumor was diagnosed by (1) positive findings on cerebrospinal fluid cytology, (2) leptomeningeal or subependymal enhancement on magnetic resonance imaging, or (3) pathological evidence of leptomeningeal tumor. We recorded whether treatment directed against the leptomeninges was given. Cerebrospinal fluid was examined in 86 of 96 patients at diagnosis and 29 of 42 at recurrence. The incidence of leptomeningeal tumor was 42% at diagnosis and 41% at recurrence. Only elevated levels of protein and lactate dehydrogenase isoenzyme-5 were significantly associated with leptomeningeal tumor (r = 0.012, p = 0.016, respectively). Treatment against the leptomeninges was significantly associated with the probability of achieving a complete response and a longer freedom from relapse. Patients older than 50 years had a worse disease-specific survival but a similar probability of responding to therapy as younger patients. Our data show that leptomeningeal tumor in priMarchy central nervous system lymphoma is more prevalent than originally thought, and indicate the need for therapy inclusive of the leptomeninges in all patients.