[Fatal flecainide intoxication in a 17-year-old girl]. / Tödliche Flecainidintoxikation eines 17-jährigen Mädchens.

A 17-year-old girl was found vomiting and somnolent at home and was taken to a hospital. The girl initially presented with ventricular tachycardia with broad QRS complexes which was very difficult to control. During the course a subsequent cardiogenic shock developed and despite exhaustion of all therapeutic options the fatal outcome could not be averted. The medicolegal autopsy revealed no evidence of any form of violence but the signs of medical treatment. Furthermore, no pathology of internal organs was detected. The toxicological analyses revealed a lethal intoxication with flecainide as the cause of death. The investigations of the police indicated that the girl took flecainide in suicidal intention.

Neuropsychological predictors of rapidly progressive Alzheimer's disease.

OBJECTIVE: Alzheimer's disease (AD), the most common cause of dementia, typically shows a slow clinical progression over time. 'Rapidly progressive' AD, a variant of the disease characterized by an aggressive course, exhibits distinct clinical, biological, and neuropathological features. Here, we investigate neuropsychological predictors of rapid decline in a group of mild patients with AD. METHODS: One hundred fifty-three mild patients with AD admitted to a memory disorder clinic and followed for up to 3 years were included in this study. A comprehensive neuropsychological (NP) battery was performed at the time of enrollment. Patients were defined as 'rapidly progressive' if they exhibited a drop of 6 or more points on the Mini Mental State Examination (MMSE) between two consecutive annual visits. This event defined the main outcome in multiple analyses of variance and Cox proportional hazards models that investigated the impact of NP predictors. Categorical principal component analysis (CATPCA) was also employed in order to delineate clusters of NP tests and to test their effect on the outcome. RESULTS: Of 153 subjects, thirty-seven (24%) were classified as 'rapidly progressive'; those subjects showed younger age of symptoms onset compared to slow decliners (68 vs 71.5 years old). Baseline lower performance on a neuropsychological test of naming predicted a rapid decline over the follow-up (P = 0.001). Three clusters of NP were defined by CATPCA: (i) executive/language, (ii) visuospatial memory, and (iii) verbal memory. The executive/language component predicted a rapid decline over the follow-up (P = 0.016). CONCLUSION: Early executive/language impairment is highly predictive of a rapid progression of AD.

Binge eating and fast cognitive worsening in an early-onset bvFTD patient carrying C9ORF72 expansion.

An expanded hexanucleotide (GGGGCC) repeat in a non-coding promoter region of open reading frame 72 of chromosome 9 (C9ORF72) has been recently identified as a major cause of familial and sporadic frontotemporal lobar degeneration. We describe the clinical picture of a 64-year-old woman carrying the hexanucleotide repeat expansion, who developed a sporadic early-onset form of behavioral variant frontotemporal dementia characterized by the occurrence of uncommon behavioral manifestations such as binge eating disturbance and by a rapid worsening of cognitive abilities. Our report confirms previous studies asserting that C9ORF72 repeats may sustain heterogeneous clinical syndromes.

A three-gene signature marks the time to locoregional recurrence in luminal-like breast cancer.

BACKGROUND: Gene expression profiling (GEP)-based prognostic signatures are being rapidly integrated into clinical decision making for systemic management of breast cancer patients. However, GEP remains relatively underdeveloped for locoregional risk assessment. Yet, locoregional recurrence (LRR), especially early after surgery, is associated with poor survival. PATIENTS AND METHODS: GEP was carried out on two independent luminal-like breast cancer cohorts of patients developing early (≤5 years after surgery) or late (>5 years) LRR and used, by a training and testing approach, to build a gene signature able to intercept women at risk of developing early LRR. The GEP data of two in silico datasets and of a third independent cohort were used to explore its prognostic value. RESULTS: Analysis of the first two cohorts led to the identification of three genes, CSTB, CCDC91 and ITGB1, whose expression, derived by principal component analysis, generated a three-gene signature significantly associated with early LRR in both cohorts (P value <0.001 and 0.005, respectively), overcoming the discriminatory capability of age, hormone receptor status and therapy. Remarkably, the integration of the signature with these clinical variables led to an area under the curve of 0.878 [95% confidence interval (CI) 0.810-0.945]. In in silico datasets we found that the three-gene signature retained its association, showing higher values in the early relapsed patients. Moreover, in the third additional cohort, the signature significantly associated with relapse-free survival (hazard ratio 1.56, 95% CI 1.04-2.35). CONCLUSIONS: Our three-gene signature represents a new exploitable tool to aid treatment choice in patients with luminal-like breast cancer at risk of developing early recurrence.

Serotonin toxicity: a short review of the literature and two case reports involving citalopram.

The serotonin toxicity (ST) is a potentially life-threatening adverse drug reaction results from therapeutic drug use, intentional self-poisoning, or inadvertent interactions between drugs. ST can be caused by a single or a combination of drugs with serotonergic activity due to excessive serotonergic agonism on central nervous system and peripheral serotonergic receptors (monoamine oxidase inhibitors, tricyclic antidepressants, SSRIs, opiate analgesics, over-the-counter cough medicines, antibiotics, weight-reduction agents, antiemetics, antimigraine agents, drugs of abuse, H2-antagonist and herbal products). The serotonin toxicity is often described as a clinical triad of mental-status changes (agitation and excitement with confusion), autonomic hyperactivity (diaphoresis, fever, tachycardia, and tachypnea), neuromuscular abnormalities (tremor, clonus, myoclonus, and hyperreflexia) and, in the advanced stage, spasticity; not all of these findings are consistently present. In this article, we describe two cases of ST due to interaction between Citalopram and two CYP2D6 inhibitors: Cimetidine and Topiramate and their clinical resolution after treatment discontinuation.

The London APP mutation (Val717Ile) associated with early shifting abilities and behavioral changes in two Italian families with early-onset Alzheimer's disease.

BACKGROUND/AIMS: Mutations in the amyloid precursor protein gene were the first to be recognized as a cause of Alzheimer's disease (AD). METHODS: We describe 2 Italian families showing the missense mutation in exon 17 of the amyloid precursor protein gene on chromosome 21 (Val717Ile), known as London mutation. RESULTS: In 1 family, this mutation was responsible for AD in 3 out of 7 siblings and it is also present in a fourth sibling who has only shown signs of executive dysfunction so far. Two subjects of the other family with AD diagnosis were carriers of the same mutation. CONCLUSION: All AD subjects showed a cognitive profile characterized by early impairment in long-term memory, shifting abilities and affective symptoms beginning in the fifth decade of life.

A descriptive study on constructional impairment in frontotemporal dementia and Alzheimer's disease.

BACKGROUND AND PURPOSE: Frontotemporal dementia (FTD) is a degenerative disorder characterized, in its frontal variant, by psychiatric onset, deficits in executive functions and sparing of memory and visuo-spatial abilities. Studies on visuo-spatial abilities in FTD and Alzheimer's disease (AD) have mainly focused on constructional abilities (CA) and have yielded contrasting data, often depending either on the task used or biases in the clinical selection of patients. The aim of our study was to evaluate the frequency of the CA impairment in FTD-fv and AD patients at the early stage of the disease, and to verify if some distinctive features of this impairment can characterize each pathology. METHODS: The copy-drawing task (Rey Complex Figure, RCF) of 41 patients with probable mild AD and 15 patients with probable mild FTD-fv were analysed by means of quantitative and qualitative indices. RESULTS: Data showed that both AD and FTD patients displayed similar RCF scores, as well as execution strategies, type of errors and global analysis. The FTD group only had a significant deficit in the analysis of inner details.

Sirolimus, Tacrolimus and Zotarolimus eluting stents to treat bifurcated lesions: a 7-month clinical outcome comparison.

AIM: Drug eluting stents (DES) have been shown to reduce restenosis compared with bare metal stents in bifurcated lesions. The aim of this study was to evaluate the long-term clinical outcomes of patients with bifurcated lesions treated by 3 different DES. METHODS: Consecutive patients with symptomatic coronary artery disease on one bifurcated lesion with SB>2.25 mm (on visual estimation) undergoing at the Department of Cardiology of the Catholic University of Rome, Italy were screened. Patients treated with Sirolimus-eluting stent (Cypher Select; SES Group), Tacrolimus-eluting stent (Taxus-Libertè; TA Group) and Zotarolimus-eluting stent (Endeavor Driver; ZOT Group) were enrolled in the study. Clinical and angiographic characteristics of all patients were prospectively recorded. Major adverse clinical events (MACE), including death, acute myocardial infarction (MI) or target lesion revascularization (TVR) by either percutaneous coronary intervention (PCI) or coronary surgery were recorded during the follow-up. Incidence of definite or probable stent thrombosis was calculated according to the ARC criteria. RESULTS: Two hundred and forty-one consecutive patients were enrolled (89 Group CY, 98 Group TA and 54 Group EN). Length of follow-up was 235+/-60 days. Baseline clinical and angiographic characteristic were similar across the groups. The adopted technique for stent implantation was provisional stenting (73.4%), T-stenting technique (7%), crush (7%) and V-stenting (2.6%). The rate of patients finally treated with two stents was similar among groups. The cumulative rate of MACE (9% SES, 12% TA, 11% ZOT: P=0.7) and of TVR (2% SES, 9% TA, 7% ZOT) was similar among groups. No definite stent thrombosis was observed during follow-up, while 1 probable stent thrombosis was observed in TA group. CONCLUSION: The clinical outcome of bifurcated lesions using DES and mainly a technique of single stent implantation is good. In the present observational study, clinical adverse events did not differ in patients with bifurcated lesions treated by Cypher, Taxus or Endeavor stent implantation.

[Assessment of the risk of arm repetitive movements among workers in the motor vehicle glass finishing industry]. / Valutazione del rischio da movimenti ripetitivi dell'arto superiore in addetti alla rifinitura di vetri per autoveicoli.

The aim of the study was to evaluate risk associated with biomechanical overload of the upper limbs in workers exposed to repetitive movements, employed to the finishing of glasses for motor vehicles. The risk assessment was performed using the OCRA method (OCRA index for every worker and Check-List OCRA for every workstation) and the results have been distributed for exposure levels. Altogether the results suggested the existence of risk associated with repetitive movements of the upper limbs and different risk classes (high, medium, light, very light). OCRA index and Check-List OCRA values showed together high risk in the workers with age and employment duration great (respectively 20.68% e 27.58% of workers), with especially involvement of the women, employed to jobs with high frequency.

Phenotypic characterization of mononuclear inflammatory cells in salivary glands of bio-breeding rats.

The purpose of this study was to assess whether mononuclear cell abnormalities exist in salivary glands from autoimmune Bio-Breeding (BB) rats. Frozen sections of gland tissues were prepared from five diabetes-resistant BB rats (BB-DR), from five BB rats with diabetes (BB-DP) and from five Wistar rats. A panel of six monoclonal antibodies was used to identify membrane antigens associated primarily with monocytes (ED1), mature tissue macrophages (ED2), lymphoid macrophages (ED3), MHC class II (Ia) antigen (OX6), CD5+ T lymphocytes (OX19), and rat B lymphocytes (OX33). Normal submandibular, sublingual and parotid glands contained few ED1-positive cells, usually two or fewer per field. Tissue macrophages identified by clone ED2 comprised a major mononuclear cell subset in both Wistar and BB rats. However, the number of ED2-positive mononuclear cells was significantly depressed in the submandibular and parotid glands from BB-DR and BB-DP animals, being present in quantities 25-50% of those observed in glands from normal Wistar rats (p < 0.001). In contrast, 25- to 30-fold greater numbers of ED3-positive macrophages were observed in submandibular glands from BB rats (p < 0.001). MHC class II (Ia) antigen expression also was 4- to 6-fold greater in BB rat submandibular glands, compared to Wistar rats (p < 0.001). CD5+ T-lymphocytes were rare or entirely absent in BB sublingual glands (0 to 1 cell per 0.87 mm2 field), compared to 47 cells per field from Wistar sublingual glands. No B lymphocytes were identified with antibody OX33 in any of the rat strains. These findings indicate that BB rat salivary glands differ significantly from Wistar salivary glands. In BB rats there is a rich population of ED3-positive macrophages and T lymphocytes in submandibular gland, low quantities of T lymphocytes in sublingual gland, and fewer ED2-positive macrophages in all three major salivary glands. These differences in mononuclear cell subpopulations may also influence salivary gland function in mucosal immunity.

Early diastolic time intervals during hypertensive pregnancy.

Early diastolic time intervals have been assessed by means of the echopolycardiographic method in 17 pregnant women who developed hypertension during pregnancy (HP) and in 14 normal pregnant women (N). Systolic time intervals (STI), stroke volume (SV), ejection fraction (EF), and mean velocity of myocardial fiber shortening (VCF) were also evaluated. Recordings were performed in the left lateral decubitus (LLD) and then in the supine decubitus (SD). In LLD, isovolumic relaxation period (IRP) was prolonged in the hypertensive pregnant women compared with normal pregnant women (HP 51 +/- 12.5 ms, N 32.4 +/- 15 ms p less than 0.05), whereas time of the mitral valve maximum opening (DE) was not different in the groups. There was no difference in SV, EF, and mean VCF, whereas STI showed only a significant (p less than 0.05) lengthening of pre-ejection period (PEP) in HP. When the subjects shifted from the left lateral to the supine decubitus position, left ventricular ejection time index (LVETi) and SV decreased significantly (p less than 0.05) in both normotensive hypertensive pregnant women. IRP and PEP lengthened significantly (p less than 0.05) only in normals, whereas they were unchanged in HP. DE time did not vary in either group. In conclusion, hypertension superimposed on pregnancy induces lengthening of IRP, as well as of PEP, and minimizes the effects of the postural changes in preload on the above-mentioned time intervals.

[THe use of leuprolide in endometrial glandular hyperplasia]. / Impiego del leuprolide acetato nelle iperplasie ghiandolari dell'endometrio.

Endometrial hyperplasia is a very frequent pathology during menopause and involves the risk of the malignant transformation of lesions and the onset of anemia due to concomitant clinical phenomena. Standard medical treatments often involve major collateral effects which impede their long-term use. In an attempt to avoid radical surgery for many women or the use of other invasive techniques, this paper proposes the use of Leuprolide acetate which was used to treat 30 patients with histologically confirmed symptoms of endometrial hyperplasia without atypia. This controlled-session LHRH analog was administered using an intramuscular route every 30 days for 6 months. Hysteroscopic and histological controls were carried out 30 days after the last treatment and showed the resolution of histological and clinical symptoms; this was confirmed after 3 months. Fibroma, which are the most frequently associated pathology, were considerably reduced.

[Recurrence of Crohn disease, complicated by intestinal perforation, during pregnancy. Discussion of a clinical case]. / Morbo di Crohn riacutizzato nel corso della gravidanza e complicato da perforazione intestinale libera. Discussione di un caso clinico.

We describe a case of Crohn's disease which came up before pregnancy and which is responsible of an acute abdomen picture caused by intestinal reacutation and perforation to the 38th week of amenorrhea. The relations between the disease and the pregnancy state are analyzed from the clinical, diagnostic and therapeutical aspect.

[Noninvasive evaluation of cardiac index and ejection fraction in ischemic heart disease. Comparison of thoracic bioimpedance, thermodilution and cineventriculography]. / Valutazione non invasiva dell'indice cardiaco e della frazione di eiezione nella cardiopatia ischemica. Confronto tra bioimpedenza toracica, termodiluizione e cineventricolografia.

Aim of the study was to verify the reliability of thoracic bioimpedance cardiography (TEB) in detection, non-invasively, cardiac index (IC) and ejection fraction (FE), compared to simultaneous evaluation by invasive thermodilution (TD) in 39 patients with acute myocardial infarction in Killip class I-II (group I), and by cineventriculography (CVG) in 26 patients with chronic coronary artery disease in NYHA class I-II (group II). In order to define the reproducibility of TEB values, in the latter patients, the above mentioned parameters were evaluated 6 times more, running the first evaluation. The statistical analysis was performed by the linear regression test and the Student's "t" test and by the test of variance for the reproducibility evaluation. Results (mean +/- SD) were as follows: group I: TEB-IC 2.89 +/- 0.63; TD-IC 2.83 +/- 0.56 (1/min/m2); r = 0.68; p < 0.01. Group II: TEB-IC 2.88 +/- 0.71; CVG-IC 3.48 +/- 0.66; r = 0.77; p < 0.001; TEB-FE 57.7 +/- 6.8%; CVG-FE 58.1 +/- 13.7%; r = 0.40; p = ns. Results of the reproducibility referred to the 6 measurements (mean +/- SD) were the follows: TEB-IC (1/min/m2) (1) 2.83 +/- 0.76; (2) 2.85 +/- 0.73; (3) 2.8 +/- 0.79; (4) 2.83 +/- 0.71; (5) 2.87 +/- 0.81; (6) 2.88 +/- 0.8, p = ns, the variability was assesses within +/- 9.3%. TEB-FE (%): (1) 56.7 +/- 6.2; (2) 55.8 +/- 5; (3) 57.1 +/- 5.5; (4) 56.1 +/- 6.1; (5) 55.4 +/- 5.8; (6) 57.3 +/- 6.3, p = ns; the variability was assessed within +/- 9.1%. The analysis of the results showed a good correlation in the IC detection among TEB and the compared techniques, conversely TEB evaluation of FE appear of poor values in this kind of patients. Relatively to the results of the reproducibility this unquestionable characteristic of TEB was demonstrated.

[Survival in post-infarction heart rupture. A case report. Role of echocardiography in immediate diagnostic approach]. / Sopravvivenza da rottura di cuore post-infartuale. Su un caso di nostra osservazione. Ruolo dell'ecocardiografia per un immediato approccio diagnostico.

A case of acute myocardial infarction of the inferior-posterior and lateral wall of the left ventricle, complicated at the onset with cardiogenic shock and myocardial rupture of the free wall, is presented. The precise and immediate echocardiographic diagnosis made it possible, by means of appropriate pharmacologic support, to reach a satisfactory haemodynamic balance in order to send the patient to decisive surgical operation.

Phenotypic characterization of mononuclear cells from gingiva associated with periodontitis and peri-implantitis.

The purpose of this study was to compare the phenotypic distribution of resident gingival mononuclear inflammatory cells from tissues associated with peri-implantitis and periodontitis. Inflamed gingiva was obtained from six patients during surgical removal of failed dental implants. Similarly, inflamed gingiva around teeth was obtained from eight patients with moderate to advanced periodontitis. Monoclonal antibodies were used to identify membrane antigens from CD4+ T-lymphocytes, CD4+/CD8(+)-activated T-lymphocytes, tissue macrophages, CD20+ B-lymphocytes, and MHC class II (Ia) antigens. Gingival inflammation associated with both dental implants and natural teeth was characterized by substantial numbers of CD4+ T-lymphocytes, resident macrophages, and B-lymphocytes. In addition, there was an abundance of HLA class II-positive mononuclear cells throughout most specimens. These results suggest that the gingival mononuclear inflammatory response in peri-implantitis and periodontitis is similar and support the hypothesis that similar inflammatory mechanisms are associated with both conditions.

Spermatozoa of an Old World Ricinulei (Ricinoides karschii, Ricinoidae) with notes about the relationships of Ricinulei within the Arachnida.

The ultrastructure of spermatozoa is a valuable tool for phylogenetic and systematic studies. Ricinulei are enigmatic and poorly studied arachnids. So far, spermatozoa are only known from New World ricinuleids. The goals were to study, by means of light and transmission electron microcopy, the spermatozoa of an Old World species with regard to their phylogenetic implications, e.g., does the sperm structure contribute to the debated sister-group relationship of Acari and Ricinulei. The spermatozoa are coiled-flagellate and characterized by a cap-like acrosomal vacuole covered by electron-dense material, an elongated nucleus covered by a manchette of microtubules during spermiogenesis, an axoneme with a 9+2 microtubular pattern, a nuclear tube and axonemal basis which both originate underneath the acrosomal vacuole and cleistospermia as transfer form equipped with three intracellular plates. The data of the present study did not support a close relationship of Ricinulei and Acari which have aflagellate sperm with various synapomorphies as e.g., lacking nuclear envelopes/membranes in Actinotrichida (very similar to Solifugae) or vacuolated spermatozoa in Anactinotrichida. Affinities of Ricinulei are discussed in the light of the ultrastructure of arachnid spermatozoa.