Classical and anaplastic seminoma: difference in survival

Classical and anaplastic seminoma are traditionally treated with radiation therapy and are said to have the same prognosis. A retrospective study was undertaken of 90 seminoma patients treated with radiation therapy between 1961 and 1985. The classical group consisted of 71 patients of whom 50 had stage I and 21 had stage II disease. The anaplastic group consisted of 19 patients of whom ten had stage I and nine had stage II disease. The median follow-up time was 64 months for the entire group. The 10-year relapse-free survival rate for the classical group was 94% and for the anaplastic group was 70% (P less than .05). For patients with classical stage I disease, the relapse-free actuarial survival rate was 98%; for patients with anaplastic stage I disease, it was 64% (P less than .02). For the classical stage II disease group, the relapse-free actuarial survival rate was 84% and for the anaplastic stage II disease group, 75% (P less than .70). Four patients in the classical group (6%) had relapses; of these, one patient had local recurrence of tumor, and three had distant metastases. In the anaplastic group, four patients (21%) had relapses; two patients had local recurrence of tumor, and two had distant metastases. Therefore the data suggest a difference in survival and relapse rates between classical and anaplastic seminoma.     

Massive Weight Loss Obtained by Bariatric Surgery Affects Semen Quality in Morbid Male Obesity: a Preliminary Prospective Double-Armed Study

Objectives

The aim of this study is to evaluate the effect of massive weight loss on the seminal parameters at 6 months from bariatric surgery.

Design

Two-armed prospective study performed in 31 morbidly obese men, undergoing laparoscopic roux-en-Y-gastric bypass (n = 23) or non-operated (n = 8), assessing sex hormones, conventional (sperm motility, morphology, number, semen volume), and non-conventional (DNA fragmentation and seminal interleukin-8), semen parameters, at baseline and after 6 months from surgery or patients’ recruitment.

Results

In operated patients only, a statistically significant improvement in the sex hormones was confirmed. Similarly, a positive trend in the progressive/total sperm motility and number was observed, though only the increase in semen volume and viability was statistically significant (Δ = 0.6 ml and 10%, P < 0.05, respectively). A decrease in the seminal interleukin-8 levels and in the sperm DNA fragmentation was also present after bariatric surgery, whereas these parameters even increased in non-operated subjects. Age-adjusted multivariate analysis showed that the BMI variations significantly correlated with the changes in the sperm morphology (β = ?0.675, P = 0.025), sperm number (β = 0.891, P = 0.000), and semen volume (r = 0.618, P = 0.015).

Conclusion

The massive weight loss obtained with bariatric surgery was associated with an improvement in some semen parameters. The correlations found between weight loss and semen parameter variations after surgery suggest that these might occur early downstream of the testis and more slowly than the changes in the sex hormones.

     

A single-blind, randomized comparison of olanzapine at a starting dose of 5 mg versus 20 mg in acute schizophrenia

Acute psychotic episodes represent critical situations during the course of schizophrenia. Olanzapine (OLZ), a second-generation antipsychotic, is efficacious in acute settings at dosages of 5 to 20 mg/d, and it can be considered a first-line treatment for patients with an acute episode of schizophrenia. The aim of this study was to evaluate the efficacy and tolerability of OLZ at a starting dose of 5 mg versus 20 mg in acute schizophrenic patients and to compare titration versus nontitration.Fifty-one schizophrenic inpatients were randomly assigned to receive OLZ at 5 mg/d (26 patients, group 1) or 20 mg/d (25 patients, group 2) as a starting dosage during an exacerbation phase. In group 1, the OLZ dosage was increased to a mean dosage of 10.55 (+/- 4.00) mg/d. Group 2 received OLZ at a fixed dose of 20 mg throughout the hospitalization period.Olanzapine was significantly and clinically effective on Brief Psychiatric Rating Scale (BPRS), Positive and Negative Syndrome Scale, PANSS positive symptoms, and Hamilton Rating Scale for Depression in both groups. There were no significant differences between groups 1 and 2 in the percent improvement in BPRS, Positive and Negative Syndrome Scale, PANSS positive symptoms, PANSS negative symptoms, or Hamilton Rating Scale for Depression; but group 2 was significantly superior in the mean percent improvement in the BPRS items of anxiety (P < 0.001) and suspiciousness (P < 0.05).In conclusion, the higher doses evidence more efficacy on anxiety and suspiciousness, so it seems to be useful to begin therapy with a full dose of the drug to obtain the maximum effect without any significant side effects.     

Histamine H3 receptor-mediated impairment of contextual fear conditioning and in-vivo inhibition of cholinergic transmission in the rat basolateral amygdala

We investigated the effects of agents acting at histamine receptors on both, spontaneous release of ACh from the basolateral amygdala (BLA) of freely moving rats, and fear conditioning. Extensive evidence suggests that the effects of histamine on cognition might be explained by the modulation of cholinergic systems. Using the microdialysis technique in freely moving rats, we demonstrated that perfusion of the BLA with histaminergic compounds modulates the spontaneous release of ACh. The addition of 100 mm KCl to the perfusion medium strongly stimulated ACh release, whereas, 0.5 microm tetrodotoxin (TTX) inhibited spontaneous ACh release by more than 50%. Histaminergic H3 antagonists (ciproxifan, clobenpropit and thioperamide), directly administered to the BLA, decreased ACh spontaneous release, an effect fully antagonized by the simultaneous perfusion of the BLA with cimetidine, an H2 antagonist. Local administration of cimetidine alone increased ACh spontaneous release slightly, but significantly. Conversely, the administration of H1 antagonists failed to alter ACh spontaneous release. Rats receiving intra-BLA, bilateral injections of the H3 antagonists at doses similar to those inhibiting ACh spontaneous release, immediately after contextual fear conditioning, showed memory consolidation impairment of contextual fear conditioning. Post-training, bilateral injections of 50 microg scopolamine also had an adverse effect on memory retention. These observations provide the first evidence that histamine receptors are involved in the modulation of cholinergic tone in the amygdala and in the consolidation of fear conditioning.     

Visual adaptation and novelty responses in the superior colliculus

The brain's ability to ignore repeating, often redundant, information while enhancing novel information processing is paramount to survival. When stimuli are repeatedly presented, the response of visually sensitive neurons decreases in magnitude, that is, neurons adapt or habituate, although the mechanism is not yet known. We monitored the activity of visual neurons in the superior colliculus (SC) of rhesus monkeys who actively fixated while repeated visual events were presented. We dissociated adaptation from habituation as mechanisms of the response decrement by using a Bayesian model of adaptation, and by employing a paradigm including rare trials that included an oddball stimulus that was either brighter or dimmer. If the mechanism is adaptation, response recovery should be seen only for the brighter stimulus; if the mechanism is habituation, response recovery ('dishabituation') should be seen for both the brighter and dimmer stimuli. We observed a reduction in the magnitude of the initial transient response and an increase in response onset latency with stimulus repetition for all visually responsive neurons in the SC. Response decrement was successfully captured by the adaptation model, which also predicted the effects of presentation rate and rare luminance changes. However, in a subset of neurons with sustained activity in response to visual stimuli, a novelty signal akin to dishabituation was observed late in the visual response profile for both brighter and dimmer stimuli, and was not captured by the model. This suggests that SC neurons integrate both rapidly discounted information about repeating stimuli and novelty information about oddball events, to support efficient selection in a cluttered dynamic world.     

Test–retest repeatability of [18F]Flortaucipir PET in Alzheimer’s disease and cognitively normal individuals

The aim of this study was to investigate the test–retest (TRT) repeatability of various parametric quantification methods for [¹⁸F]Flortaucipir positron emission tomography (PET). We included eight subjects with dementia or mild cognitive impairment due to Alzheimer’s disease and six cognitively normal subjects. All underwent two 130-min dynamic [¹⁸F]Flortaucipir PET scans within 3 ± 1 weeks. Data were analyzed using reference region models receptor parametric mapping (RPM), simplified reference tissue method 2 (SRTM2) and reference logan (RLogan), as well as standardized uptake value ratios (SUVr, time intervals 40–60, 80–100 and 110–130 min post-injection) with cerebellar gray matter as reference region. We obtained distribution volume ratio or SUVr, first for all brain regions and then in three tau-specific regions-of-interest (ROIs). TRT repeatability (%) was defined as |retest–test|/(average (test + retest)) × 100. For all methods and across ROIs, TRT repeatability ranged from (median (IQR)) 0.84% (0.68–2.15) to 6.84% (2.99–11.50). TRT repeatability was good for all reference methods used, although semi-quantitative models (i.e. SUVr) performed marginally worse than quantitative models, for instance TRT repeatability of RPM: 1.98% (0.78–3.58) vs. SUVr_80–100: 3.05% (1.28–5.52), p < 0.001. Furthermore, for SUVr_80–100 and SUVr_110–130, with higher average SUVr, more variation was observed. In conclusion, while TRT repeatability was good for all models used, quantitative methods performed slightly better than semi-quantitative methods.     

Données épidémiologiques sur le lien entre cancers et pesticides

Pesticides encompass a wide variety of chemical agents used extensively in occupational and domestic settings. Their potential impact on human health has been analysed in many epidemiological studies of farmers. In general, the cancer risk is lower in farmers because this population consists of a smaller proportion of smokers, although there is a higher incidence of some cancer sites: lips, prostate gland, brain, and blood. Pesticides probably play a role in these occurrences, but it has not been possible to determine definitively the specific active ingredients or chemical families. Existing studies are limited in scope, especially because of difficulties assessing exposure. Improvements in tools and methods are needed. Large cohorts of farmers will also help to expand present knowledge.     

Intracranial bleeding: epidemiology and relationships with antithrombotic treatment in 241 cerebral hemorrhages in Reggio Emilia

BACKGROUND AND OBJECTIVES: Anticoagulant (AC) and antiplatelet (AP) drugs are effectively used in the prevention of thromboembolic events, with the trade-off of bleeding side effects, particularly intracranial. The aim of this study was to determine the incidence of intracranial bleeding in the population of Reggio Emilia and to investigate the potential effect of AC and AP drugs. DESIGN AND METHODS: We reviewed all the patients admitted for cerebral hemorrhages to our hospital between April 1998 and September 2000. Data were collected with a standardized form. All the patients were followed-up to estimate long-term mortality. Chi(2) and t-tests were used as appropriate. Logistic regression analysis was performed to test predictors of mortality. Pharmaceutical department data were employed to estimate the total number of patients receiving AC and AP drugs. RESULTS: We found 241 cases (107/134 female/male, mean age 61 years, 133/107 spontaneous/traumatic events, 0.32/1,000/year overall). Twenty-nine and 47 of these patients were being given AC or AP drugs, respectively (4.9/1,000/year and 3.7/1,000/year). The relative risk of intracranial bleeding was 11.5 in AP and 15.3 in AC treated patients. Two patients (one underwent neurosurgery and one thrombolytic treatment) were excluded from mortality and risk factors analysis. Six patients were lost from follow-up and excluded from mortality analysis. Overall mortality was 100/233 (42.9%); mortality in traumatic events was 25/103 (24.2%) versus 75/130 (57.7%) in spontaneous events. Mortality was 19/29 (65.5%), 26/47 (55.3%) and 55/157 (35%) in AC recipients, AP recipients, and untreated patients, respectively. This increased risk was mainly confined to traumatic events (p = 0.06), without difference between AC and AP recipients. At the time of the event, the mean duration of oral AC treatment was 26.3 months (range 1-120). Mean INR was = 3.1 (range 1.6-8.8). Mortality was significantly predicted by the Glasgow Coma Scale Score (GCS) at admission (p < 0.0001), by the type of bleeding (spontaneous versus traumatic) (p = 0.0026), and by age (p < 0.0001). INTERPRETATION AND CONCLUSIONS: Careful selection of patients and prevention of traumatic events are the main candidate mechanisms to reduce intracranial bleeding in patients being treated with AC and AP drugs.     

Adult porcine islet transplantation in baboons treated with conventional immunosuppression or a non-myeloablative regimen and CD154 blockade

The aim of the present study was to assess the survival of adult porcine islets transplanted into baboons receiving either (I) conventional triple drug immunosuppressive therapy or (2) a non-myeloablative regimen and an anti-CD154 monoclonal antibody (mAb) aimed at tolerance-induction. Group 1 baboons (n = 3) were pancreatectomized prior to intraportal injection of 10,000 porcine islet equivalents (IE)/kg and immunosuppressed with anti-thymocyte globulin (ATG), cyclosporine and azathioprine. In Group 2 (n = 2), non-pancreatectomized baboons underwent induction therapy with whole body and thymic irradiation, and ATG. Extracorporeal immunoadsorption (EIA) of anti-Galalpha1,3Gal (Gal) antibody was carried out. Maintenance therapy was with cobra venom factor, cyclosporine. mycophenolate mofetil, methylprednisolone and anti-CD154 mAb. Porcine islets were injected intraportally (14,000 and 32,000 IE/kg, respectively) and high-dose pig mobilized peripheral blood progenitor cells (3 x 10(10) cells/kg) were infused into a systemic vein. Porcine islets were also implanted in the sternomastoid muscle to facilitate subsequent biopsies. In both groups. porcine C-peptide was measured, and histological examination of liver or sternomastoid muscle biopsies was performed at regular intervals. In Group 1, total pancreatectomy reduccd human C-peptide to < 0.1 ng/ml and induced insulin-requiring diabetes. The transplantation of porcine islets was followed by normalization of glycemia for 15-24 h. Porcine C-peptide was detected only transiently immediately after porcine islet injection (maximum 0.12 ng/ml). Histological examination of liver biopsies taken between days 2 and 19 did not reveal viable islets, but necrotic cell structures with mononuclear cell infiltrates were identified in portal venules. In Group 2, injection of porcine islets into non-pancreatectomized recipients induced a transient hypoglycemia (2-4 h) requiring concentrated intravenous dextrose administration. Porcine C-peptide was detectable for 5 and 3 days (maximum 2.8 and 1.0 ng/ml), respectively. Baboon #4 died on day 12 from small bowel intussusception. Liver and sternomastoid muscle biopsies showed well-preserved porcine islets, staining positive for insulin and glucacon, without signs of rejection. In baboon #5, viable islets were detected in the sternomastoid muscle biopsy on day 14, but not on day 28 or thereafter. A progressive mononuclear cell and macrophage infiltration was seen in the biopsies. In conclusion, conventional immunosuppression allowed survival of porcine islets in baboons for < 24 h. The non-myeloablative regimen prolonged survival of porcine islets for > 14 days. However, despite depletion of T cells, anti-Gal antibody and complement, and CD154-hlockade, porcine islets were rejected by day 28. These results suggest that powerful innate immune responses are involved in rejection of discordant xenogencic islets.