BRAF V599E mutation occurs in Spitz and Reed naevi.
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Biomedical subjects
Publications and source records attributed to C Clemente.
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Familial amyloid polyneuropathy (FAP) is an inherited amyloidosis mainly associated with transthyretin Val30Met variant. Clinical heterogeneity has been reported in different populations with FAP and Va130Met variant. In order to characterize FAP expression in Brazilians and to compare its features to those reported in other cohorts, 44 Brazilian patients (27 females, median age 36 [23-53] years) with FAP and the Val30Met variant were investigated. Approximately 40% of their family members, with the exception, of parents and siblings, had FAP. Most of the patients had symptoms of peripheral neuropathy at onset. Median age at onset was 32 [20-44] years. Earlier onset was observed in males (27 [20-43] years in males vs. 33 [20-44] years in females, P = 0.02) and in patients whose parents had FAP (31 [20-44] years vs. 40 [37-43] years in patients, respectively with and without affected parents, P = 0.03). Phenotypic expression of FAP in Brazil is similar to the one reported in Portugal, characterized by high disease penetrance, early onset, particularly in males and in subjects with affected parents, and major symptoms of peripheral neuropathy. These data highlight the influence of common genetic factors, shared by both groups of patients, in disease expression.
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This study explores the rate of psychosocial dysfunction in affected and unaffected children from families with haemophilia or beta-thalassaemia, as part of a cross-sectional, multicentre study into the resilience of 115 families with blood disorders. Sociodemographic and developmental data were collected from the parents using a standardized and semi-structured interview format, and medical data were obtained from the clinician. The children's social functioning over the year prior to the assessment was assessed with The Social Adjustment Scale adapted for school-aged children. Children with beta-thalassaemia showed significantly higher rates of social dysfunction than their unaffected siblings or children with haemophilia and their siblings. Older children showed significantly higher social dysfunction at school. The high rate of social dysfunction in children with beta-thalassaemia compared with unaffected siblings is likely to have a basis in the negative experiences associated with their medical problems. In contrast, the therapeutic advances in haemophilia allows boys to lead an almost normal life. Overall, the rates of social dysfunction in families with both these disorders proved commoner than reported in population surveys, but with the unavailability of local population controls, caution needs to be exercised in the interpretation of this finding.
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BACKGROUND: This study examines the prevalence of psychiatric disorders in affected and in unaffected siblings from families with haemophilia or beta-thalassaemia. METHOD: Based on data derived from a cross-sectional and multi-centre study into the resilience of 115 families with blood disorders. Sociodemographic and developmental data were collected from the parent using a standardised and semi-structured interview, and medical data were elicited from the attending clinician. The children's psychopathology was assessed with the Schedule for Affective Disorders and Schizophrenia (K-SADS). RESULTS: Children with beta-thalassaemia were twice as likely to receive a diagnosis of psychiatric disorder and more likely to show a higher degree of impairment of general functioning than haemophilic boys or unaffected children from families with blood disorders. Clinical severity of haemophilia or beta-thalassaemia was not associated with significant differences in prevalence of child psychiatric disorders or impairment. Mothers' evaluation of their relationship with their child as 'less than easy' predicted psychopathology. CONCLUSIONS: The high prevalence of psychopathology in children with beta-thalassaemia reported in this study suggests that specific blood disorders have differential impact on affected children. This difference may be related to medical therapy advances in haemophilia so that haemophilic boys can lead an almost normal life.
PURPOSE: To evaluate the effects of pregnancy on gastrointestinal function, we determined gastric emptying time, orocecal transit time, and fasting gastrointestinal hormone levels (cholecystokinin, gastrin, pancreatic polypeptide, neurotensin) in 11 women with mild dyspeptic symptoms during the first and third trimesters of their pregnancies, and again 4-6 months after delivery. METHODS: After the women ingested a disaccharide solution, orocecal transit time was determined by monitoring breath hydrogen concentrations at 10-min intervals, and values were compared with the postpartum value. Ultrasound examinations of gastric emptying were performed during the same intervals. RESULTS: The half-emptying time and the final gastric emptying time did not differ in the first and third trimesters and postpartum, but gastrointestinal transit time was significantly longer in the third trimester of pregnancy than postpartum (100.0 min [range, 50.5-240.0 min] vs 70.0 min [range, 40.5-240.0 min; P < 0.05]), respectively. Mean plasma pancreatic polypeptide values were lower in the third trimester of pregnancy than postpartum. and a negative correlation was observed between pancreatic polypeptide levels and transit time in the third trimester (r = -0.65; P = 0.0261). The plasma levels of other gastrointestinal hormones did not differ in the various periods studied. CONCLUSIONS: Our study shows that, despite evident dyspeptic symptoms, there were no significant alterations in gastric emptying or orocecal transit time during the first trimester of pregnancy. Conversely, in the third trimester, orocecal transit time was significantly longer.
There is no general agreement as regards the effect of Helicobacter pylori infection on gastric emptying in patients with functional dyspepsia. Food releases several gastrointestinal hormones, and some of these are known to contribute to the regulation of gastric emptying. The aim of this study was to investigate the influence of H. pylori on gastric emptying in dyspeptic and healthy subjects and to verify whether different hormone secretion patterns are affected by the presence of the bacterium. Twenty-seven patients affected by functional dyspepsia and 30 asymptomatic healthy subjects entered the study. H. pylori presence was assessed in controls by IgG antibodies to H. pylori and [13C] urea breath test, and that in patients by Warthin-Starry stain on gastric biopsies. After ingesting a standard solid-liquid meal, an ultrasound examination of gastric emptying was performed. Plasma concentrations of gastrin, cholecystokinin, and pancreatic polypeptide were measured in the fasting and postprandial period for 4 hours. The incidence of H. pylori infection was not higher in functional dyspepsia patients than in controls. As regards gastric emptying, no difference was detected between patients and controls with and without H. pylori infection. On the contrary, the presence of H. pylori infection determined alterations in gastrin levels, which were higher in controls than in patients. Basal CCK levels were higher in the H. pylori-negative patients than H. pylori-positive patients and controls. In conclusion, H. pylori infection seems not to cause alterations in gastric emptying, but rather alterations in gastrin levels. In contrast, the altered levels of CCK account for its involvement in the pathophysiology of H. pylori-negative dyspepsia.
AIM: To compare the feeding patterns and difficulties of infants with congenital heart disease (CHD) and healthy controls. Information was gathered via parental questionnaires. METHODS: A matched case controlled study of 64 infants with CHD compared with 64 healthy controls. RESULTS: The main findings were: (1) Feeding patterns: mothers with infants with CHD used bottle-feeding as a first method of feeding their babies more often (CHD, 20%, controls, 2%); (2) Specific feeding difficulties: (a) infants with CHD were significantly more breathless when feeding (CHD = 16%, controls, 0%), (b) had more vomiting at mealtimes (CHD = 23%, controls = 11%), but (c) had significantly less spitting (CHD = 19%, controls, 41%); and (3) infants with CHD showed significantly reduced growth. CONCLUSIONS: The feeding difficulties are related to the organic condition and not specific difficulties in mother-infant interaction. Professional support may be required for mothers of infants with CHD to maintain feeding routines and to deal with the difficulties that arise.
The Gordian knot of anatomy has been the architectural arrangement of ventricular muscle mass, which may have finally become understood. The description of Francisco Torrent-Guasp's model of the helical heart is presented, which includes the cardiac structures that produce 2 simple loops that start at the pulmonary artery and end in the aorta. An unscrolled ventricular band is shown, achieved by blunt dissection that extends between the points of origin of the right ventricle, at the pulmonary artery root, to termination at the aortic root, in the left ventricle. These components include a spiral horizontal basal loop that surrounds the right and left ventricular cavities, and changes direction to cause a second spiral, produced by almost vertically oriented fibers, giving rise to the helical configuration of the ventricular myocardial band. These anatomic structures are successively activated, as with a peristaltic wave, starting at the right ventricle (just below the pulmonary artery) and progressing toward the aorta to produce a sequence of narrowing, caused by the basal loop contraction, shortening (related predominantly to the descendant segment contraction), lengthening (produced by the ascendant segment contraction), and widening, as a consequence of several factors that act during ventricular myocardium relaxation. These sequences control the ventricular events responsible for ejection to empty and suction to fill. These mechanical interactions of structure and function are defined in relation to chronologic location of the successive cardiac functional events in the aortic, left ventricular, and left atrial recordings.
Torrent-Guasp's model of the helical heart is presented, which includes the cardiac muscular structures that produce 2 simple loops and that start at the pulmonary artery and end in the aorta. These components include a horizontal basal loop that surrounds the right and left ventricles, changes direction through a spiral fold in the ventricular band to cause a ventricular helix produced by now obliquely oriented fibers, forming a descending and ascending segment of the apical loop with an apical vortex. These anatomic concepts are successively activated to produce a sequence of narrowing by the basal loop, shortening by the descending segment, lengthening by the ascending segment, and widening in the cardiac cycle that causes ventricular ejection to empty and suction to fill. The factors responsible for internal torsional movements for cardiac output and suction are defined, together with mechanisms responsible for electromechanical activity produced during sequential changes in contraction and relaxation properties. These interactions of mechanical structure and function are defined in relation to pressure-related cardiac events observed from aortic, left ventricular, and left atrial recordings.
The pathophysiology of hypergastrinemia in H. pylori infection has been largely investigated and different reports clearly show that the infected antrum has a marked inflammatory response with a suggestive local production of cytokines. Notwithstanding, a few data are available on the circulating levels of cytokines and gastrin in the asymptomatic people carrying H. pylori infection. Thus, aim of the study was to evaluate circulating proinflammatory cytokines [Interleukin (IL)-8, Interleukin (IL)-10, Interferon (IFN)-gamma, and Tumor Necrosis Factor (TNF)-alpha] and gastrin levels in H. pylori positive asymptomatic subjects vs. H. pylori negative ones. To this end, thirty healthy volunteers with no digestive symptoms or systemic disease were enrolled and H. pylori infection was identified by a 13C-urea breath test. Plasma levels of gastrin were determined using the RIA kit whereas IL-8, TNF-alpha, IL-10, and IFN-gamma levels in serum were measured with a solid-phase ELISA. Fifteen infected people showed significantly higher gastrin and TNF-alpha levels than uninfected subjects. On the contrary, IL-8 levels were significantly higher in the uninfected subjects than in H. pylori positive ones (P < 0.0422). IFN-gamma and IL-10 circulating levels were not affected by H. pylori presence, being not significantly different in the two groups.
AIMS: To explore the patterns of gastric electrical activity, gastric emptying and gastrointestinal hormones in dyspeptic patients and relate them to Helicobacter pylori status. METHODS: Twenty-two patients with functional dyspepsia and 29 healthy volunteers underwent cutaneous electrogastrography and dynamic ultrasound before and after a test meal. All dyspeptic patients underwent endoscopy and biopsy; all subjects were examined for the presence of antibodies to H. pylori, and the plasma levels of gastrin, neurotensin, cholecystokinin, and pancreatic polypeptide were measured. RESULTS: The area under the curve (AUC) of the normal slow wave percentage was lower in dyspeptic patients than controls (Kruskal-Wallis p = 0.016; Dunn's test: H. pylori-positive patients: 21,235.5 [19,101.0-22,688.8] vs. H. pylori-negative controls: 22,532.0 [20,133.0-23,755.0], p < 0.05). The AUC of the tachygastria percentage was higher in dyspeptic patients than controls (p = 0.0001; H. pylori-positive patients: 2,173.5 [325.8-3,055.3] vs. H. pylori-negative controls: 682.0 [118.5-1,902.4], p < 0.05; H. pylori-negative patients: 1,843.0 [1,107.0-4,277.0] vs. H. pylori-negative controls: 682.0 [118.5-1,902.4], p < 0.05). The AUC of gastrin was higher in H. pylori-positive than H. pylori-negative subjects (p = 0.0002; H. pylori-positive patients: 16,146.5 [11,368.8-33,141.7] vs. H. pylori-negative controls: 11,250.0 [5,674.0-17,448.0], p < 0.05; H. pylori-positive controls: 20,250.0 [12,070.0-64,430.0] vs. H. pylori-negative controls: 11,250.0 [5,674.0-17,448.0], p < 0.05). In the total group of dyspeptic patients and in the H. pylori-positive patients, a negative correlation was found between the AUC of neurotensin and the total score for postprandial fullness (dyspeptic patients r = -0.51, p = 0.01; H. pylori-positive patients r = -0.66, p = 0.02). CONCLUSIONS: In dyspeptic patients, alterations in gastric electrical activity were not related to H. pylori infection. Nevertheless, H. pylori infection induces higher gastrin levels in both patients and asymptomatic subjects.
The aim of the present study was to assess whether a telemicroscopy system based on static imaging could provide a remote intraoperative frozen section service. Three pathologists evaluated 70 consecutive frozen section cases (for a total of 210 diagnoses) using a static telemicroscopy system (STeMiSy) and light microscopy (LM). STeMiSy uses a robotic microscope, enabling full remote control by consultant pathologists in a near real-time manner. Clinically important concordance between STeMiSy and LM was 98.6% (95.2% overall concordance), indicating very good agreement. The rates of deferred diagnoses given by STeMiSy and LM were comparable (11.0% and 9.5%, respectively). Compared with the consensus diagnosis, the diagnostic accuracy of STeMiSy and LM was 95.2% and 96.2%. The mean viewing time per slide was 3.6 minutes, and the overall time to make a diagnosis by STeMiSy was 6.2 minutes, conforming to intraoperative practice requirements. Our study demonstrates that a static imaging active telepathology system is comparable to dynamic telepathology systems and can provide a routine frozen section service.
From January 1993 to May 2000, 1062 patients with primary cutaneous melanoma and no evidence of clinically detectable regional node metastases underwent sentinel node (SN) dissection to microscopically define the tumor status of the regional lymph nodes. A total of 1165 biopsies were performed. The SN identification rate was 89.6%. In 62.2% of the cases, only one SN was detected; 26.4% of patients had two SNs; and 11.4% had three or more SNs. Analysis of survival indicated that the tumor status of the nodes was the most important prognostic factor. Breslow's thickness had a significant impact on survival in tumors 4 mm or thicker, and ulceration dropped to a borderline-significant P value. To assess the tumor burden in positive SNs, all slides for patients at the Istituto Nazionale Tumori and S. Pio X Hospital were reviewed. Of 658 patients in this series, 90 had positive SNs. Eighteen of these patients had evidence of metastasis in other nodes. Of the remaining 72 with a single tumor-involved SN, 62% had a single metastatic deposit. Preliminary data from this study indicate that several subgroups may be identified among patients with positive nodes, but adequate analysis of survival requires a larger number of patients and a multicenter study.
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BACKGROUND: Tadenan (a Pygeum africanum extract) is a drug used in the treatment of benign prostatic hyperplasia. Its effects on prostate fibroblast proliferation and bladder function after partial outlet obstruction have been demonstrated in various pharmacological studies. However, its effects at the molecular level are poorly documented. METHODS: Tadenan was dissolved in peanut oil. Rats were orally given two daily doses of the drug (1 or 10 mg/kg b.w.) for 4 days. Vasoactive intestinal peptide (VIP) binding, adenylyl cyclase stimulation, and expression of G-protein subunits were studied in rat prostatic membranes by established procedures. RESULTS: Tadenan treatment of castrated/testosterone-replaced rats was performed in order to interfere with prostatic cell proliferation. This experimental approach resulted in increases of: 1) VIP effect on adenylyl cyclase stimulation through alpha(s) G-subunit; 2) alpha(i) activation by low Gpp[NH]p doses (in the presence of forskolin); and 3) alpha(s), alpha(i1/2), and alpha(i3/0) levels. However, there were no modifications in membranes from quiescent, nonproliferating prostates (untreated rats). CONCLUSIONS: The observed regulatory role of Tadenan on various prostatic components of the adenylyl cyclase system, together with previous findings on protein kinase C-mediated signal transduction, open a complex array of possibilities of direct actions of this phytotherapeutic agent in the prostate.