Level of use of 3,4-methylenedioxymethamphetamine (MDMA or Ecstasy) in humans correlates with EEG power and coherence

Rationale: Despite animal studies implicating 3,4-methylenedioxymethamphetamine (MDMA or Ecstasy) in serotonergic neurotoxicity, there is little direct evidence of changes in neural function in humans who use MDMA as a recreational drug. Objective: The present study investigated whether there is a correlation between quantitative EEG variables (spectral power and coherence) and cognitive/mood variables, and level of prior use of MDMA. Methods: Twenty-three recreational MDMA users were studied. Resting EEG was recorded with eyes closed, using a 128-electrode geodesic net system, from which spectral power, peak frequency and coherence levels were calculated. Tests of intelligence (NART), immediate and delayed memory, frontal function (card sort task), and mood (BDI and PANAS scales) were also administered. Pearson correlation analyses were used to examine the relationship between these measures and the subject’s consumption of MDMA during the previous 12-month period. Partial correlation was used to control for the use of other recreational drugs. Results: MDMA use was positively correlated with absolute power in the alpha (8–12 Hz) and beta (12–20 Hz) frequency bands, but not with the delta (1–3 Hz) or theta (4–7 Hz) bands. MDMA use was negatively correlated with EEG coherence, a measure of synchrony between paired cortical locations, in posterior brain sites thought to overly the main visual association pathways of the occipito-parietal region. MDMA use did not correlate significantly with any of the mood/cognitive measures except the card sort task, with which it was weakly negatively correlated. Conclusions: Alpha power has been shown to be inversely related to mental function and has been used as an indirect measure of brain activation in both normal and abnormal states. Reduced coherence levels have been associated with dysfunctional connectivity in the brain in disorders such as dementia, white-matter disease and normal aging. Our results may indicate altered brain function correlated with prior MDMA use, and show that electroencephalography may be a cheap and effective tool for examining neurotoxic effects of MDMA and other drugs. Received: 19 October 1998/Final version: 12 January 1999     

Antihyperglycaemic effect of saccharin in diabetic ob/ob mice

1. The effect of chronic saccharin (benzosulphimide) consumption on glucose homeostasis was examined in normal lean +/+ mice and genetically obese hyperglycaemic insulin-resistant ob/ob mice.
2. Consumption of a 5% (w/v) sodium saccharin solution for 7 weeks prevented the development of hyperglycaemia, improved glucose tolerance (area under curve decreased by 51%), reduced the extent of hyperinsulinaemia (by 21%), and reduced excessive weight gain (by 18%) in ob/ob mice.
3. Consumption of 5% (w/v) sodium saccharin temporarily decreased hyperphagia at the beginning of treatment, decreased hepatic glycogen content (by 47%), increased abdominal muscle glycogen content (by 82%), but did not significantly alter the hypoglycaemic response to exogenous insulin in ob/ob mice.
4. Consumption of a 1% (w/v) sodium saccharin solution did not prevent the development of hyperglycaemia in ob/ob mice.
5. Normal lean +/+ mice consuming 5% (w/v) sodium saccharin solution showed a marginal decrease (by 8%) in glycaemia, and glucose tolerance was improved (area under curve decreased by 30%) without a significant change in the insulin response to glucose or the hypoglycaemic effect of exogenous insulin.
6. The results suggest that chronic consumption of saccharin can defer the development of hyperglycaemia and improve glucose homeostasis in insulin-resistant ob/ob mice through a mechanism that is independent of insulin.

     

The effect of chronic administration of a synthetic LH-RH analogue intranasally in cryptorchid boys

Eighteen boys with either unilateral or bilateral cryptorchidism were treated with a synthetic LH-RH analogue ("D-Leu 6, Des-Gly-10 LH-RH ethylamide") intranasally. The peptide was dissolved in aqueous solution (25 micrograms in 0,2 ml) and administered in the form of nasal drops. The patients were divided in two groups: in group A, 50 micrograms of the synthetic LH-RH analogue were administered intranasally every 48 h for 36 days; in group B same dose was given every 24 h. Additionally, in 4 cases a LH-RH test prior the trial was performed with the same peptide. The nasal administration resulted in a fivefold increase of LH and of FSH plasma concentration in 30 min and in 60 min, respectively. The endocrine profiles for T, LH and FSH were studied in each group over the treatment period and in group B (same dose was given every 24 h) a significant decrease of the LH and FSH plasma levels could be found. The clinical effect of treatment was same in the both groups. In the whole material 44% had either unilateral or bilateral descent of the testis after the therapy.     

Effect of active immunization to luteinizing-hormone-releasing hormone on the fertility and histoarchitecture of the reproductive organs of male rat

Summary The feasibility of using a vaccine against luteinizing-hormone-releasing factor for supression of pituitary and gonadal functions has been indicated for some time. Antibody production against this low-molecular-weight, naturally occurring decapeptide, however, requires to be coupled to a carrier protein to enhance its immunogenicity. LHRH was coupled to diphtheria toxoid (DT). Adult male Sprague-Dawley rats with a mean basal body weight of 200g were immunized with anti-LHRH-DT (20 g/injection/rat) at four-week intervals. An equal number of unexposed animals served as controls. Six animals were killed every two weeks up the end of the week 43. The vaccination schedule did not have any effect on the gain in body weight, nor was any adverse effect of vaccination observed in the course of the investigations. The pituitary, prostate, epididymis, testes, seminal vesicles, adrenal and thyroid were excised for determination of organ weight and histological examination. The adrenal, pituitary and thyroid showed no remarkable weight changes during the observation period, whereas the weights of the reproductive organs demonstrated significant reductions compared to those of the control group. The histopathology revealed marked to significant changes in the gonads and the accessory sex organs including the prostate. A progressive phase of regeneration of spermatogenesis was evident 98 days after vaccination. Total recovery of spermatogenesis was observed 300 days after vaccination. The mating studies showed the return of fertility 300 days after vaccination. The litters borne were normal. Prostate showed recovery after 154 days of vaccination. Our observations lend strong support to the hypothesis that anti-LHRH vaccine can be effectively used on the management of prostate carcinoma. If the vaccination is given together with a suitable dose of long-acting androgen, contained in an adequate delivery system, the regimen may be used for the regulation of male fertility.     

The Effect of Calcium Channel Antagonists on Spontaneous and Evoked Epileptiform Activity in the Rat Neocortex In Vitro

Calcium influx through voltage-activated calcium channels may play a crucial role in the propagation and maintenance of seizure activity. We have examined the contribution of various types of calcium currents to epileptogenesis by studying the effects of various calcium channel blockers on epileptiform activity. N-methyl-d-aspartate receptor-mediated epileptiform activity was induced by removal of magnesium ions superfusing the cortex, or by low-frequency stimulation of the underlying white matter. CoCl2, CdCl2 and omega-conotoxin, acting at the N- and L-type calcium channels, significantly reduced epileptiform activity. L-channel antagonists nifedipine and verapamil, and the agonist BAY K 8644, increased spontaneous bursting in cortical wedges, but had no effect upon evoked activity. The T-channel blocker NiCl2 had variable effects on epileptiform activity, whereas phenytoin consistently reduced such activity. These results suggest that calcium influx underlying epileptiform activity in the rat neocortex may occur at least partially via the activation of the N-type calcium channel. However, contributions from other calcium channel types cannot be excluded.     

The effect of temperature on copper tolerance ofParamecium

Summary The copper tolerance ofParamecium tetraurelia decreases with increased temperatures over the range of 12 C to 34 C. The relationship is linear and the correlation=–0.98. The regression equation has an intercept of 16 M Cu⁺⁺ at 0 C, and tolerance is reduced by 0.33 M for each degree increase in temperature.     

Frontal dysfunction in schizophrenia – a new electrophysiological classifier for research and clinical applications

We determined whether schizophrenic patients can be reliably classified with electrophysiological tools. We developed a fully computerized classifier based on 5 minutes of EEG recording during an acoustical choice reaction time task (AMDP-module IV). We included factorized variables from the frequency domain and evoked potentials (N100/P200-complex) from central and frontal electrodes, which were preprocessed in a sample of 150 normal subjects prior to classification. We applied discriminant analyses to the electrophysiological data from depressive, schizophrenic and schizotypal subjects, most of them being unmedicated or drug-naive. The classifier was developed on a training set (33 schizophrenics, 49 normals) and tested on an independent sample (32 schizophrenics, 49 normals). A simple three-variable classifier was found to classify schizophrenics and normals in 77% of those tested correctly. Diagnostic specificity of the classifier proved to be low as the inclusion of depressive patients (n= 60) significantly decreased classification power. It was demonstrated that atypical but not typical neuroleptic drugs may influence the classification results. Correctly classified schizophrenics showed significantly more negative symptoms and slower reaction times than those schizophrenics who were misclassified as normals. In contrast, these misclassified schizophrenics showed a non-significant trend for more positive symptoms and shorter reaction times. As the correctly classified schizophrenics showed increased frontally pronounced delta-activity and decreased signal power of the N100/P200 amplitude, it was concluded that these schizophrenics show dysfunction of the frontal lobe. It is proposed that this new classifier can be useful for clinical and research applications when subtyping of schizophrenics with detection of frontal dysfunction as the aim.     

Ten-year outcomes in a population-based cohort of node-negative, lymphatic, and vascular invasion-negative early breast cancers without adjuvant systemic therapies.

PURPOSE: To discuss the absolute benefits from adjuvant systemic therapy knowledge of long-term outcomes and baseline risks of relapse and disease-specific survival are required. We assessed the 10-year outcomes in a population-based cohort of node-negative (N-) lymphovascular negative (LV-) early breast cancers diagnosed from 1989 to 1991 who did not receive adjuvant systemic therapy. METHODS: One thousand one hundred eighty-seven cases of pT(1-2)N(0) LV- breast cancers with a median follow-up of 10.4 years were reviewed. Kaplan-Meier survival curves for relapse free survival (RFS), breast cancer-specific survival (BCSS) and overall survival (OS) were compared with log-rank tests with cohorts stratified for tumor size and grade. RESULTS: The median age of this series was 62 years. Four hundred thirty tumors were < or = 1 cm in diameter (cohort 1), 507 were 1.1-2 cm (cohort 2), and 250 were 2.1 to 5 cm in diameter (cohort 3). The 10-year outcomes for cohorts 1, 2, and 3, respectively, were significantly different: RFS, 82%, 75%, and 66%; BCSS, 92%, 90%, and 77%; and OS, 79%, 78%, and 66%. Tumor grade significantly altered outcome within size cohorts, particularly in pT(1)N(0) breast cancers. CONCLUSION: This study provides detailed information on the continued relapse and breast cancer death rate to 10 years of follow-up. Specifically, without adjuvant systemic therapy, patients with LV-, N - breast cancer had a > or = 25% 10-year risk of relapse and a corresponding 10-year breast cancer death rate of > or = 10% if they had either a grade 3 tumor < or = 1 cm, a grade 2 to 3 tumor from 1.1 to 2 cm, or any grade tumor greater than 2 cm.     

Localized pelvic neuroblastoma: excellent survival and low morbidity with tailored therapy--the 10-year experience of the French Society of Pediatric Oncology.

PURPOSE: To assess the results and morbidity of treatment of children with localized pelvic neuroblastoma (NB). PATIENTS AND METHODS: All consecutive cases of localized pelvic NB registered in the French multicenter prospective studies NBL90 and NBL94 between 1990 and 1999 were reviewed. Resectability was decided on the basis of clinical and radiologic evaluation. In unresectable tumors, primary chemotherapy (combinations of carboplatin-etoposide and vincristine-cyclophosphamide-doxorubicine) was administered before surgery. RESULTS: Forty-seven children (with 26 resectable tumors and 21 unresectable) were included in this study. At the end of treatment, 31 children were in complete remission (66%). Long-term neurologic sequelae were observed in seven patients (15%), directly attributable to surgery in three cases. After a median follow-up of 48 months (range, 13 to 129 months), 44 patients are alive. Six children experienced local relapse; four of these children achieved subsequent remission. The projected overall survival and event-free survival (EFS) rates at 5 years are, respectively, 93% +/- 4% and 84% +/- 5%. Survival of children treated with preoperative chemotherapy are similar to those treated by primary surgery (80% and 88% respectively). The extent of surgical resection seemed to have no influence on the outcome (EFS rates 76% and 89% in case of gross residue and complete resection or microscopic residue, respectively). CONCLUSION: Our data confirm the excellent survival of localized pelvic NBs. Considering the efficacy of preoperative chemotherapy, patients with pelvic NB should be carefully screened for primary surgery. The risk of neurologic impairment during radical excision should be balanced with the good survival of children with minimal residual disease.     

Wolfe's parenchymal pattern and percentage of the breast with mammographic densities: redundant or complementary classifications?

Mammographic breast densities are one of the strongest breast cancer risk factors. The two most frequently used classifications of breast densities are Wolfe's parenchymal pattern and the percentage of the breast with densities. In this analysis, associations of these two classifications with breast cancer risk were compared, and the dose response curve of risk with densities was examined. Three case-control studies were combined totaling 1060 cases with newly diagnosed breast cancer and 2352 controls. A single observer had assessed parenchymal pattern and percent density without any information on subjects. Relative risks (RRs) were estimated with logistic regression and spline functions adjusting for age and body weight. The two classifications were strongly correlated (r = 0.81, P = 0.0001). Breast cancer risk increased progressively with percent density reaching a 5-6-fold increase for women with 85% or more of the breast with densities compared with women with no density. In contrast, women with P2 or DY patterns had only a 2-3-fold increase in risk compared with women with N1 pattern. More importantly, among women with P2 or DY, RR varied substantially with percent density, whereas, among women with a given percent density, RR varied little with parenchymal pattern. Comparisons of multivariate models reveal that in the presence of parenchymal pattern, inclusion of percent density in the model improved the prediction of breast cancer risk (chi(2) = 35.5, P = 0.0082) but not the opposite (chi(2) = 1.1, P = 0.7662). These findings show that the percentage of the breast with densities provide more information on breast cancer risk than Wolfe's parenchymal patterns and that, once percent breast density is taken into account, no more information on breast cancer risk is given by assessing parenchymal pattern.