Exocytosis-related genes and response to methylphenidate treatment in adults with ADHD.

Experimental studies have demonstrated that methylphenidate (MPH) modulates the synaptic vesicle trafficking and synaptotagmin-1 (SytI) mRNA levels. SytI is a regulatory protein of the SNARE complex, a neurotransmitter exocytosis mediator. Despite this evidence, most SNARE complex-related genes have never been evaluated in attention-deficit/hyperactivity disorder (ADHD) pharmacogenetics. This study evaluates, for we believe the first time, polymorphisms on the SNARE complex-related genes STX1A (rs2228607), VAMP2 (26bp Ins/Del) and SYT1 (rs1880867 and rs2251214) on the response to immediate-release methylphenidate (IR-MPH) in a naturalistic sample of adults with ADHD. The sample comprised 433 subjects, of which 272 (62.8%) have completed the short-term IR-MPH treatment (at least 30 days). The main outcome measure was the categorical variable of short-term response to IR-MPH based on the Swanson, Nolan and Pelham Rating Scale version 4 (SNAP-IV), and on the clinical global impression-improvement scale. Additional analyses evaluated the percentage of SNAP-IV symptom reduction for each dimension as well as short- and long- (7 years) term treatment persistence. SYT1-rs2251214 was associated with the categorical short-term response to IR-MPH (P=0.006, PFDR=0.028), and with the percentage of inattention and oppositional defiant disorder symptoms reduction (P=0.007, PFDR=0.028 and P=0.017, PFDR=0.048, respectively). SYT1-rs2251214 was also associated with short-term treatment persistence (P=0.018, PFDR=0.048), and with months of treatment (P=0.002, PFDR=0.016) in the long-term protocol. Our findings suggest that SYT1-rs2251214 presents a broad influence in IR-MPH response variability in adults with ADHD, being involved with both symptom response and treatment persistence. If such findings are replicated, SytI could represent a key element in MPH pharmacodynamics in adults with ADHD.

Role of ACE and AGT gene polymorphisms in genetic susceptibility to diabetes mellitus type 2 in a Brazilian sample.

The aim of the current study was to investigate the association between the InDel polymorphism in the angiotensin I-converting enzyme gene (ACE) and the rs699 polymorphism in the angiotensinogen gene (AGT) and diabetes mellitus type 2 (DM2) in a sample population from Southern Brazil. A case-control study was conducted with 228 patients with DM2 and 183 controls without DM2. The ACE InDel polymorphism was genotyped by polymerase chain reaction (PCR) with specific primers, followed by electrophoresis on 1.5% agarose gel. The AGT rs699 polymorphism was genotyped using a real-time PCR assay. No significant association between the ACE InDel polymorphism and DM2 was detected (P = 0.97). However, regarding the AGT rs699 polymorphism, DM2 patients had a significantly higher frequency of the AG genotype and lower frequency of the GG genotype when compared to the controls (P = 0.03). Our results suggest that there is an association between the AGT rs699 polymorphism and DM2 in a Brazilian sample.

Is there a role for rare variants in DRD4 gene in the susceptibility for ADHD? Searching for an effect of allelic heterogeneity.

Although several studies have demonstrated an association between the 7-repeat (7R) allele in the 48-bp variable number of tandem repeats (VNTRs) in the exon 3 at dopamine receptor D4 (DRD4) gene and attention-deficit/hyperactivity disorder (ADHD), others failed to replicate this finding. In this study, a total of 786 individuals with ADHD were genotyped for DRD4 exon 3 VNTR. All 7R homozygous subjects were selected for VNTR re-sequencing. Subjects homozygous for the 4R allele were selected paired by age, ancestry and disorder subtypes in order to have a sample as homogeneous as possible with 7R/7R individuals. Using these criteria, 103 individuals (66 with ADHD and 37 control individuals) were further investigated. An excess of rare variants were observed in the 7R alleles of ADHD patient when compared with controls (P=0.031). This difference was not observed in 4R allele. Furthermore, nucleotide changes that predict synonymous and non-synonymous substitutions were more common in the 7R sample (P=0.008 for total substitutions and P=0.043 for non-synonymous substitutions). In silico prediction of structural/functional alterations caused by these variants have also been observed. Our findings suggest that not only repeat length but also DNA sequence should be assessed to better understand the role of DRD4 exon 3 VNTR in ADHD genetic susceptibility.

Histologic patterns of primary malignant tumors of the fallopian tube.

From 1978 through 1993 four patients underwent surgical treatment of primary fallopian tube rumors. Mean age was 62.5 years. A different histologic pattern was found in each cases: transitional, endometrioid, serous papillary and malignant mixed mesodermal tumor. Prognostic significance of histologic patterns is underlined together with grade and stage; all our cases were included in stage IA. Surgical treatment was, in all cases, hysterectomy with bilateral salpingo-oophorectomy; in two cases an adjunctive chemotherapy followed. A second look was performed in two cases. All patients are alive and free of disease with a follow-up varying from 15 to 84 months.

[Computerized evaluation of reparative processes of the cervix uteri]. / Valutazione computerizzata dei processi riparativi del collo uterino.

This study was aimed to evaluate the effect of polydeoxyribonucleotide (PDRN), as reported in relevant literature, on cervical epithelia dynamics. Particularly, the interactions taking place between columnar epithelium and the squamous one have been examined. For the purposes of the study, the following computerized techniques, already widely known, have been used: The colposcope is joined to a videocamera connected with a computer (AT compatible). The computer is equipped with a graphic card capable to record and to digit the image, i.e. to make it recognizable by the computer itself. Thereafter, many operations can be performed on the colposcopic images: reductions, enlargements, retouches, record, recall, analysis, etc. Moreover, irregular epithelial areas can be easily determined to a good approximation and, using pre-established enlargement ratios, their evolution can be evaluated. By means of this technique 12 out-patients with uterine cervix ectopias, with or without normal transformation zone (NTZ), have been examined. The monthly therapy was 12 pessaries, each containing 5 mg polydeoxyribonucleotide (POLIDES 5--Farmigea), from the 7th to the 18th day of the cycle, repeated for 3 months. Since the first month of treatment a reduction of the ectopic columnar epithelium has been noted in most patients (9 on 12), with a squamous epithelium increase (peripheral reparative process). This process has kept on increasing during the following months in the 9 patients responding to the treatment, whose ectopic areas were covered by squamous epithelium (average 55% of the area; range 33%-78%). No response to the treatment has been shown in 3 cases.(ABSTRACT TRUNCATED AT 250 WORDS)

Colposcopy and computer graphics: a new method?

A new method is herein described that uses the most recent computer science techniques to obtain digitalized colposcopic images that may be useful not only as documents, but also as research tools. Because computer graphics is a recent and ever-growing discipline, our method, too, might undergo considerable improvements: some possible improvements are hypothesized in the text. The most striking features of this method are the excellent quality of images, their easy reproducibility, and the reasonable cost.

Impaired ventilatory drive in short-term primary hypothyroidism and its reversal by L-triiodothyronine.

Alveolar hypoventilation is known to occur in myxedema. Reduction of hypercapnic ventilatory drive has not been reported, up to now, in patients with short-term hypothyroidism. Eleven patients with short-term hypothyroidism, before and after L-triiodothyronine (L-T3) replacement therapy, and 10 normal controls were studied. Hypercapnic ventilatory drive was assessed by the evaluation of the relation between the response of ventilation and mean expiratory flow to CO2 rebreathing and by the evaluation of ventilation and mean expiratory flow at a fixed level of carbon dioxide. In patients with short-term hypothyroidism these parameters were reduced as compared with normal controls and returned to normal after L-T3 replacement. We conclude that hypercapnic ventilatory drive is blunted by short-term hypothyroidism and normalizes following replacement therapy.

Failure of resistive breathing training to improve pulmonary function tests in patients with chronic obstructive pulmonary disease.

The effects on pulmonary function tests and exercise tolerance of resistive breathing training (RBT) were assessed in 16 subjects with stable chronic obstructive pulmonary disease (COPD) who had received no benefit from previous programs of breathing retraining (BR) and medical therapy (MT). 16 male patients with mild degree stable COPD underwent detailed evaluation of pulmonary function tests, blood gas analysis and exercise tolerance test before and after a monthly program of RBT. The patients had received no physiological effects from previous monthly programs of BR and MT. No change in pulmonary function tests, blood gas analysis and exercise tolerance test was observed after RBT. Only maximal static expiratory pressure increased significantly after RBT. We conclude that RBT does not improve pulmonary function tests in subjects who received no physiological benefit from BR.

[Obstructive peripheral athero-arteriosclerotic vascular diseases. Apparent pathogenetic role of hormono-metabolic changes]. / Vasculopatie periferiche ostruttive atero-arteriosclerotiche. Apparente ruolo patogenetico di alcune alterazioni ormono-metaboliche.

We determined by comparison, in 30 patients with arteriosclerosis obliterans and in 10 normal peoples, 50-70 years aged, the values of some glycolipidic parameters (blood glucose, triglyceridemia, cholesterolemia, nephaemia, beta- and pre-beta-lipoproteinemia) and moreover the hormonal ones (IRI, GH, cortisolemia) at fast in the morning, during the whole day and during some blocking and stimulating tests. Patients with arteriosclerosis obliterans presented a significant alteration of the lipidic outline (hyper-lipoproteinemia of IV type sec. Fredr) and of the carbohydrate metabolism, emphasized at the OGTT by a dissimilar tolerance (normal, borderline and pre-diabetic type) referring to a normal high and low insulin immission respectively. We dissert widely about biohumural data, as reflexes involved from the pancreatic function and from the ischaemic process, and we report the eventual tie between the detected hormone-metabolic disorders and the development of arteriosclerotic occlusive disease in the lower extremities.