Randomized, Crossover and Single-Dose Bioquivalence Study of Two Oral Desogestrel Formulations (Film-Coated Tablets of 75 μg) in Healthy Female Volunteers

Despite the increase in the substitution of branded medicinal product with generic drugs, this is a controversial issue for some pharmacological groups (such as contraceptives).The aim of the present clinical trial was to assess the bioequivalence and tolerability of two oral formulations of desogestrel.Thirty-three healthy female volunteers participated in this randomized and two-way crossover study. During two separate experimental periods, with at least four weeks of washout period, women received a single oral dose of 75 μg of desogestrel from each of the formulations (test formulation and reference formulation). Desogestrel bioavailability was determined by the measurement of 3-ketodesogestrel plasma concentration.Pharmacokinetic parameters were comparable and the 90% CI for the ratio of C_max (96.14–114.53%) and AUC_0–t (105.73–123.83%) values for the test and reference formulations fell within the established regulatory interval (80–125%). Both formulations were also comparable in terms of tolerability.From the results of this study it can be concluded that test formulation (desogestrel 75 μg, Cyndea PHARMA S.L.) is bioequivalent to the reference formulation (Cerazet® 75 μg, Organon Española S.A.).     

Oral health and the symptoms of schizophrenia

The objectives of this study were to evaluate the oral health of a group of schizophrenic outpatients and a control group without psychiatric illness. The study also aimed to assess the influence of positive and negative symptomatology on oral health among outpatients with schizophrenia. The DMF-T Index (sum of decayed, missing and filled teeth) and the Community Periodontal Index of Treatment Needs (CPITN) were assessed in both groups. We evaluated the psychopathological state of the patient group using the Positive and Negative Syndrome Scale (PANSS). The schizophrenic patients had higher scores than the control group with respect to decayed teeth (4.39 vs. 0.72), missing teeth (5.66 vs. 1.50), the DMF-T index (13.51 vs. 7.8) and CPITN (2.32 vs. 1.04); and lower scores for filled teeth (3.53 vs. 5.54). The PANSS negative subscale score correlated positively with the oral health variables studied, whereas the PANSS positive subscale score correlated negatively and exclusively with the number of missing teeth. Age and smoking status affected oral health in both groups, but even when the influence of these factors was considered, the oral health of the patients was poorer than that of the control group.     

Estenosis anastomóticas benignas en la cirugía radical del cáncer de recto. Resultados del tratamiento con dilatación hidrostática

IntroductionBenign anastomotic strictures after rectal cancer surgery are common and their treatment can vary from conservative measures to surgical resection.Patients and methodsBetween March 2001 and August 2008, 422 patients with rectal cancer underwent anterior resection and 83.8% were treated with primary anastomosis. Anastomotic stricture has been defined as the inability to pass a colonoscope. Hydrostatic balloon dilation was performed. Results of success and failure dilation were assessed.ResultsTwenty-six patients (7.34%) with anastomotic stricture were treated; 16 men and 10 women, with a median age of 66 years (57 – 74). A total of 26 anterior resections were performed, as well as 10 end-to-end anastomosis, 10 side-to-end, 4 j-pouch and 2 pouch coloplasties. The median stricture height was 10 cms (4 – 12). Thirteen patients had preoperative radiotherapy (50%), and 9 patients had an ileostomy (34.7%). The median time of diagnosis was 6 months (3 – 10). The diagnosis was made by: rectal digital examination in 19.2%, colonoscopy 23.1% and clinical symptoms in 57.7%. The median number of dilation sessions required was 2 (1 – 4). The median of follow-up was 39 months (23 to 49). Results were successful 88.5,% and unsuccessful in 11.5%. Morbidity was 3.8% (one perforation after dilation). There was no mortality.ConclusionsBenign anastomotic strictures after rectal cancer surgery are frequent (7.05%), develop symptoms (52.9%) and can be successfully treated by hydrostatic dilation in more than 88% patients.     

Endometrial stromal sarcoma. Is there a place for radiotherapy?

Objectives  

The optimal approach in the management of endometrial stromal sarcoma (ESS) remains unclear. The aim of the present study was to retrospectively report the outcome of patients treated for ESS in our hospital over a 27-year period in order to evaluate the treatment results and the role of radiotherapy.     

Anatomical characterization of the cannabinoid CB1 receptor in cell‐type–specific mutant mouse rescue models

Type 1 cannabinoid (CB₁) receptors are widely distributed in the brain. Their physiological roles depend on their distribution pattern, which differs remarkably among cell types. Hence, subcellular compartments with little but functionally relevant CB₁ receptors can be overlooked, fostering an incomplete mapping. To overcome this, knockin mice with cell‐type–specific rescue of CB₁ receptors have emerged as excellent tools for investigating CB₁ receptors’ cell‐type–specific localization and sufficient functional role with no bias. However, to know whether these rescue mice maintain endogenous CB₁ receptor expression level, detailed anatomical studies are necessary. The subcellular distribution of hippocampal CB₁ receptors of rescue mice that express the gene exclusively in dorsal telencephalic glutamatergic neurons (Glu‐CB₁‐RS) or GABAergic neurons (GABA‐CB₁‐RS) was studied by immunoelectron microscopy. Results were compared with conditional CB₁ receptor knockout lines. As expected, CB₁ immunoparticles appeared at presynaptic plasmalemma, making asymmetric and symmetric synapses. In the hippocampal CA1 stratum radiatum, the values of the CB₁ receptor‐immunopositive excitatory and inhibitory synapses were Glu‐CB₁‐RS, 21.89% (glutamatergic terminals); 2.38% (GABAergic terminals); GABA‐CB₁‐RS, 1.92% (glutamatergic terminals); 77.92% (GABAergic terminals). The proportion of CB₁ receptor‐immunopositive excitatory and inhibitory synapses in the inner one‐third of the dentate molecular layer was Glu‐CB₁‐RS, 53.19% (glutamatergic terminals); 2.30% (GABAergic terminals); GABA‐CB₁‐RS, 3.19% (glutamatergic terminals); 85.07% (GABAergic terminals). Taken together, Glu‐CB₁‐RS and GABA‐CB₁‐RS mice show the usual CB₁ receptor distribution and expression in hippocampal cell types with specific rescue of the receptor, thus being ideal for in‐depth anatomical and functional investigations of the endocannabinoid system. J. Comp. Neurol. 525:302–318, 2017. © 2016 Wiley Periodicals, Inc.     

At-risk brain tissue identified with arterial spin labeling in neurotuberculosis

A 13-year-old immunocompromised girl developed neurotuberculosis. Arterial spin labeling technique indicated areas of hypoperfusion in the vascular territories of the left posterior cerebral artery and superior cerebellar artery without restricted diffusion, suggesting early tuberculous arteritis. MR angiography confirmed vascular involvement, so adjunctive anticoagulant therapy was initiated. Complete resolution of arterial spin labeling findings was observed 1 month later. This documents early tuberculous vasculopathy revealed by arterial spin labeling in a child with neurotuberculosis. Since there may be a paucity of clinical symptoms in the evolution of arteritis in neurotuberculosis, arterial spin labeling may help indicate early hypoperfusion and alert for modification of treatment before irreversible vascular damage occurs.     

Episodios aparentemente letales en las primeras dos horas de vida durante el contacto piel con piel. Incidencia y factores de riesgo

Objective

To evaluate an unexpected increase in the incidence of apparently life threatening events and sudden deaths in neonates during the first 2 hours after birth in our hospital. This increase occurred in the first 2 years after generalized skin-to-skin contact between mother and infant became routine practice.

Methods

Full information on all our patients was collected to evaluate possible risk factors. Differences in incidence in four successive periods comprising the previous 35 years, with 208220 live neonates, were also analyzed.

Results

In the last period, there was a statistically significant increase in the rate of apparently life threatening events and sudden deaths in neonates. Several potential risk factors were detected: skin-to-skin contact, primiparity, an increased incidence in night hours and the invariable occurrence of these events in the second period of neonatal adaptation (30 to 90 minutes of life). Of eight patients with apparently life-threatening events, two had neurological sequelae and another died.

Conclusion

Apparently life threatening events in the first 2 hours of life are uncommon but may have serious consequences. One of the main risk factors may be skin-to-skin contact between mother and infant in the delivery room during the early adaptation period. As such contact has been proven to be beneficial and without apparent risks, this practice should be promoted. However, maternity staff should be vigilant during skin-to-skin contact, especially if the mother is alone with her neonate or other risk factors are present.     

Validity of the Severity of Dependence Scale (SDS) Construct Applying the Item Response Theory to a Non-Clinical Sample of Heroin Users

Aims: The purpose of this work is to study the validity of the Severity of Dependence Scale (SDS) construct by applying Rasch models to a non-clinical sample of heroin abusers. Subjects: 982 (73% men) young people 30 years old or under (mean age 25.9 years) participated. All of them were captured from the community in the metropolitan areas of Madrid, Barcelona and Seville, between April 2002 and December 2003. Analysis: Dimensionality of the scale and calibration of items were studied using the Rating Scale model, which is a Rasch-type model. A factorial analysis was also performed to check the dimensionality of the scale. Results: The analysis of fit shows that all the items have infit and outfit values between ± 2 logits, indicating that the data fit the model and that it may be assumed to be unidimensional. The principal components analysis also showed the existence of a principal factor that explains 52.5% of the variance observed. Item calibration found that they are between +0.89 and ?1.04 logits on the scale. Conclusion: The results show unidimensional structure of the SDS scale. Item calibration shows they are distributed along the continuum, which must be taken into account when calculating total scores. The study's limitations are noted.