Head down tilt 15° in experimental intracerebral hemorrhage: a randomized noninferiority safety trial.

BACKGROUND AND PURPOSE: Head down tilt 15° (HDT15°), applied before recanalization, increases collateral flow and improves outcome in experimental ischemic stroke. For its simplicity and low cost, HDT15° holds considerable potential to be developed as an emergency treatment of acute stroke in the prehospital setting, where hemorrhagic stroke is the major mimic of ischemic stroke. In this study, we assessed safety of HDT15° in the acute phase of experimental intracerebral hemorrhage. METHODS: Intracerebral hemorrhage was produced by stereotaxic injection of collagenase in Wistar rats. A randomized noninferiority trial design was used to assign rats to HDT15° or flat position (n = 64). HDT15° was applied for 1 h during the time window of hematoma expansion. The primary outcome was hematoma volume at 24 h. Secondary outcomes were mass effect, mortality, and functional deficit in the main study and acute changes of intracranial pressure, hematoma growth, and cardiorespiratory parameters in separate sets of randomized animals (n = 32). RESULTS: HDT15° achieved the specified criteria of noninferiority for hematoma volume at 24 h. Mass effect, mortality, and functional deficit at 24 h showed no difference in the two groups. HDT15° induced a mild increase in intracranial pressure with respect to the pretreatment values (+2.91 ± 1.76 mmHg). HDT15° had a neutral effect on MRI-based analysis of hematoma growth and cardiorespiratory parameters. CONCLUSIONS: Application of HDT15° in the hyperacute phase of experimental intracerebral hemorrhage does not worsen early outcome. Further research is needed to implement HDT15° as an emergency collateral therapeutic for acute stroke.

Anterior hippocampal dysconnectivity in posttraumatic stress disorder: a dimensional and multimodal approach.

The anterior hippocampus (aHPC) has a central role in the regulation of anxiety-related behavior, stress response, emotional memory and fear. However, little is known about the presence and extent of aHPC abnormalities in posttraumatic stress disorder (PTSD). In this study, we used a multimodal approach, along with graph-based measures of global brain connectivity (GBC) termed functional GBC with global signal regression (f-GBCr) and diffusion GBC (d-GBC), in combat-exposed US Veterans with and without PTSD. Seed-based aHPC anatomical connectivity analyses were also performed. A whole-brain voxel-wise data-driven investigation revealed a significant association between elevated PTSD symptoms and reduced medial temporal f-GBCr, particularly in the aHPC. Similarly, aHPC d-GBC negatively correlated with PTSD severity. Both functional and anatomical aHPC dysconnectivity measures remained significant after controlling for hippocampal volume, age, gender, intelligence, education, combat severity, depression, anxiety, medication status, traumatic brain injury and alcohol/substance comorbidities. Depression-like PTSD dimensions were associated with reduced connectivity in the ventromedial and dorsolateral prefrontal cortex. In contrast, hyperarousal symptoms were positively correlated with ventromedial and dorsolateral prefrontal connectivity. We believe the findings provide first evidence of functional and anatomical dysconnectivity in the aHPC of veterans with high PTSD symptomatology. The data support the putative utility of aHPC connectivity as a measure of overall PTSD severity. Moreover, prefrontal global connectivity may be of clinical value as a brain biomarker to potentially distinguish between PTSD subgroups.

The surveillance of occupational diseases in Italy: the MALPROF system.

BACKGROUND: Occupational diseases data can guide efforts to improve worker's health and safety. AIMS: To describe MALPROF, the Italian system for surveillance of work-related diseases collected by the subregional Department of Prevention. METHODS: The MALPROF system started in 1999 with contributions from Lombardy and Tuscany and spread in the following years to collect contributions from 14 out of the 20 Italian regions. MALPROF data were explored to follow-up work-related diseases and to detect emerging occupational health risks by calculating proportional reporting ratio (PRR), as in pharmacosurveillance. It classified work-related diseases according to economic sector and job activity in which the exposure occurred. Occupational physicians of the Italian National Health Service evaluate the possible causal relationship with occupational exposures and store the data in a centralized database. RESULTS: From 1999 to 2012, the MALPROF system collected about 112000 cases of workers' diseases. In 2010, more than 13000 cases of occupational diseases were reported. The most frequently reported diseases were hearing loss (n = 4378, 32%), spine disorders (n = 2394, 17%) and carpal tunnel syndrome (n = 1560, 11%). The PRR calculated for cervical disc herniation, a disease whose occupational origin has to be studied, in 1999-2010 was 2.47 [95% confidence interval (CI) 1.76-3.47] for drivers and 36.64 (95% CI 22.03-60.93) for air transport workers. CONCLUSIONS: MALPROF is a sensitive system for identifying possible associations between occupational risks and diseases, it can contribute to the development of preventive measures, to evaluate the effectiveness of preventive interventions and to stimulate research on new occupational risks and diseases.

Glycaemic fall after a glucose load. A population-based study.

BACKGROUND AND AIMS: A blood glucose (BG) fall after an oral glucose load has never been described previously at a population level. This study was aimed at looking for a plasma glucose trend after an oral glucose load for possible blood glucose fall if any, and for its impact on coronary mortality at a population level. METHODS AND RESULTS: In subjects from an unselected general population, BG and insulin were detected before and 1 and 2h after a 75-g oral glucose load for insulin sensitivity and ß-cell function determination. Blood pressure, blood examinations and left ventricular mass were measured, and mortality was monitored for 18.8±7.7 years. According to discriminant analysis, the population was stratified into cluster 0 (1-h BG < fasting BG; n=497) and cluster 1 (1-h BG ≥ fasting BG; n=1733). To avoid any interference of age and sex, statistical analysis was limited to two age-gender-matched cohorts of 490 subjects from each cluster (n=940). Subjects in cluster 0 showed significantly higher insulin sensitivity and ß-cell function, lower visceral adiposity and lower blood pressure values. Adjusted coronary mortality was 8 times lower in cluster 0 than 1 (p<0.001). The relative risk of belonging to cluster 1 was 5.40 (95% CI 2.22-13.1). CONCLUSION: It seems that two clusters exist in the general population with respect to their response to an oral glucose load, independent of age and gender. Subjects who respond with a BG decrease could represent a privileged sub-population, where insulin sensitivity and ß-cell function are better, some risk factors are less prevalent, and coronary mortality is lower.

Occupational therapy and dementia: the experience of an Alzheimer special care unit.

This trial reports the outcomes of an occupational therapy (OT) program in a group of patients with moderately severe dementia, attending a day care center. Twenty-six patients were enrolled in this therapeutic program for a 12-month period. OT sessions were held for two hour a day, five days a week. The outcomes of the trial suggest that the introduction of OT and multidimensional assessment may improve management and mediate the psychophysical decline of persons with dementia. Indeed, the assessed performance indices remained relatively stable over time, as compared to the decline expected by the natural progression of disease. Moreover, behavioral disorders evaluated by the neuropsychiatric inventory (NPI) scores improved appreciably between treatment start and end. The day care center provides an opportunity for both the person with dementia and their family by optimizing therapy for the patient and providing medical assistance for morbid conditions that ensue during the course of disease and by lowering the burden of care and providing moral support for the family by a trained staff, with particular focus on behavioral disorders that are not amenable to pharmacological management.

Clinical and genetic studies in hereditary spastic paraplegia with thin corpus callosum.

BACKGROUND: A complicated form of recessive hereditary spastic paraplegias (HSPs) with thin corpus callosum (TCC) was first described in Japan, and most of the Japanese families showed linkage to chromosome 15q13-15. A recessive HSP locus (SPG11) has also been mapped to chromosome 15q13-15 in Italian and North American families with and without TCC, and it overlaps the region identified in the Japanese families. OBJECTIVE: To study clinically and genetically 12 Italian families with HSP and TCC. METHODS: The authors investigated 18 affected and 30 healthy individuals from 12 unrelated Italian families with recessive HSP-TCC. Clinical, neurophysiologic, and neuroradiologic studies were undertaken. All patients were negative for SPG7 mutations. Genetic linkage analyses were carried out with polymorphic DNA markers on 15q13-15. RESULTS: Five families were consistent with linkage, thus defining a 19.8-cM region between markers D15S1007 and D15S978, encompassing the SPG11 interval. In one consanguineous family, linkage could be firmly excluded, confirming genetic heterogeneity. Two families appeared not linked to the region, but this could not be firmly proved because of the small family size. The remaining four families were uninformative for linkage purposes. CONCLUSION: HSP-TCC is common in Italy. The phenotype is fairly homogeneous and is associated with impaired cognition. There are at least two loci for HSP-TCC, one of which is on chromosome 15q13-15.

Migraine-like disorder segregating with mtDNA 14484 Leber hereditary optic neuropathy mutation.

The authors report neurologic features in a large family harboring the mitochondrial DNA (mtDNA) mutation T14484C associated with Leber hereditary optic neuropathy (LHON). In the maternal line the mtDNA mutation was associated with optic neuropathy or migraine with aura or without aura and transient neurologic/visual disturbances. The segregation of familiar cases of migraine and LHON mutation broadens the clinical phenotype associated with a primary LHON mutation.

Autosomal dominant external ophthalmoplegia and bipolar affective disorder associated with a mutation in the ANT1 gene.

The authors report on a family with dominantly inherited progressive external ophthalmoplegia and a diagnostic and statistical manual (fourth revised edition) diagnosis of bipolar psychiatric disorder in several members. Skeletal muscle biopsy from the proposita showed decreased cytochrome c oxidase staining, several ragged-red fibers, and multiple mtDNA deletions. The authors identified a missense mutation (leucine 98-->proline) in the adenine nucleotide translocator 1 gene. The presence of bipolar affective disorder expands the phenotype of adenine nucleotide translocator 1 allelic variants.

Arrhythmogenic right ventricular dysplasia: cardiomyopathy current opinions on diagnostic and therapeutic aspects.

Right Ventricular Dysplasia constitutes a genetic cardiomyopathy characterized by fibrous-adipose substitution of the right and rarely of the left ventricular myocardium. This disorder is associated with ventricular arrhythmias ranging from frequent ventricular ectopic beats, nonsustained and sustained ventricular tachycardia of left bundle branch morphology and sudden death. Therefore, the syndrome has been labelled Arrhythmogenic RVD Cardiomyopathy. Diagnostic criteria, preliminary genetic data, and clinical manifestations are summarized and critical addressed, using data from the literature and from our own experience. The most important aspects of the ECG in this syndrome are reviewed and stressed with particular attention to initial versus advanced clinical subsets. The typical anatomical abnormalities and biopsy or pathology material are presented.

Dihydrotestosterone prevents glucocorticoid-negative effects on fetal rat metatarsal bone in vitro.

The effects of dihydrotestosterone (DHT) on glucocorticoid-pretreated fetal rat long bone were studied in an in vitro culture system. First, dose-response curves of corticosterone, hydrocortisone, and dexamethasone were studied at several concentrations. Then, hydrocortisone (H) at 10(-5) M was selected for the second part of the study, as it slackened rudiment mineralization (104 +/- 16% of the initial dark zone vs. 141 +/- 9% in control bones), as well as its lengthening (140 +/- 4% of the harvesting day length vs. 160 +/- 1% in control bones), by both inhibition of cell proliferation and stimulation of resorption. On the contrary, in H-pretreated metatarsal bones, DHT (10(-7) M) partly limited slackening of mineralization (124 +/- 5%) and lengthening (153 +/- 2%). Moreover, a control-like cell proliferation was re-established and resorption holes were filled in. Thus, in this study, DHT partly limited hydrocortisone-induced impairment of fetal rat metatarsal bone development.

Abnormal H-Tfam in a patient harboring a single mtDNA deletion.

We report on a patient suffering from a progressive mitochondrial disorder characterized by ocular myopathy, exercise intolerance, and muscle wasting. Morphological examination of muscle biopsy showed increased variability in fiber size and scattered ragged-red fibers. Analysis of muscle mitochondrial DNA by Southern blot and PCR revealed a heteroplasmic single deletion of 4100 base pairs, located between nucleotide positions 8300 and 12,400. Western blot analysis showed high levels of the human mitochondrial transcription factor A (Tfam). Interestingly, we also detected an additional Tfam product, of approximately 22 kDa. This is the first case in which a qualitatively abnormal Tfam has been found to be associated with a mitochondrial disorder in humans.

Upright tilt test: correlation between results and patient clinical features.

The aim of our study was to analyze how the clinical history and the main clinical characteristics of patients suffering from loss of consciousness may influence the results of the upright tilt test. A series of 745 patients (333 males, 412 females; mean age 44 +/- 18 years) with recurrent episodes of syncope or presyncope underwent complete clinical and noninvasive laboratory examination, including vagal maneuvers and upright tilt test (60 degrees for 45 min). Cardiological and neurological findings were normal in every case. Upright tilt test was positive in 462 patients (62%). Patients with presyncope showed a lower positivity compared to patients with syncope (70.2% vs 42.9%, P < 0.001). Younger patients (< 25 years) displayed highest upright tilt test positivity (68.5%), while familial occurrence of syncope or presyncope, results of vagal maneuvers, and different gender did not correlate with the results of the test. The time interval between the last syncopal episode and the day of upright tilt test negatively influenced the proportion of positive tests (> 30 days = 45.1% vs < 30 days = 77.2%; P < 0.001). Patients with more than three syncopal episodes in the 2 months preceding the test showed a higher upright tilt test positivity (83.9% vs 64.5%, P < 0.001). In conclusion, upright tilt test seems to be more sensitive in young patients with syncopal episodes during symptomatic periods. These findings suggest both an individual and temporal variability in autonomic nervous system activity, the implication of which are relevant to the indications for testing as well as the analysis of results.

Familial cardiomyopathy underlies syndrome of right bundle branch block, ST segment elevation and sudden death.

OBJECTIVES: We sought to assess whether structural heart disease underlies the syndrome of right bundle branch block, persistent ST segment elevation and sudden death. BACKGROUND: Ventricular fibrillation and sudden death may occur in patients with a distinctive electrocardiographic (ECG) pattern of right bundle branch block and persistent ST segment elevation in the right precordial leads. METHODS: Sixteen members of a family affected by this syndrome underwent noninvasive cardiac evaluation, including electrocardiography, Holter ambulatory ECG monitoring, stress testing, echocardiography and signal-averaged electrocardiography; two patients had electrophysiologic and angiographic study. Endomyocardial biopsy was performed in one living patient, and postmortem examination, including study of the specialized conduction system, was performed in one victim of sudden death. RESULTS: Five years before a fatal cardiac arrest, the proband had been resuscitated from sudden cardiac arrest due to recorded ventricular fibrillation. Serial ECGs showed a prolonged PR interval, right bundle branch block, left-axis deviation and persistent ST segment elevation in the right precordial leads, in the absence of clinical heart disease. Postmortem investigation disclosed right ventricular dilation and myocardial atrophy with adipose replacement of the right ventricular free wall as well as sclerotic interruption of the right bundle branch. A variable degree of right bundle branch block and upsloping right precordial ST segment was observed in seven family members; four of the seven had structural right ventricular abnormalities on echocardiography and late potentials on signal-averaged electrocardiography. A sib of the proband also had a prolonged HV interval, inducible ventricular tachycardia and fibrofatty replacement on endomyocardial biopsy. CONCLUSIONS: An autosomal dominant familial cardiomyopathy, mainly involving the right ventricle and the conduction system, accounted for the ECG changes and the electrical instability of the syndrome.

Sudden death in mitral valve prolapse with Holter monitoring-documented ventricular fibrillation: evidence of coexisting arrhythmogenic right ventricular cardiomyopathy.

We report the case of a 42-year-old female, affected by mitral valve prolapse and ventricular arrhythmias, who died suddenly from ventricular fibrillation recorded during Holter monitoring. The lethal arrhythmia initiated with late diastolic couplets followed by a ventricular tachycardia that eventually degenerated into ventricular fibrillation. The patient had experienced four orthostatic and stress-related syncopal episodes, associated with nausea and diaphoresis, and a positive tilt test. Holter monitoring documented ventricular arrhythmias, consisting of both isolated monomorphic and sporadic repetitive beats. Her standard ECG and exercise test were normal, but signal-averaged study findings were significantly positive. QT prolongation in the absence of arrhythmias was observed during the Valsalva manoeuvre and isoproterenol infusion. 2D echo showed a remarkable mitral valve prolapse without regurgitation and localized structural abnormalities of the right ventricle. Postmortem study confirmed mitral valve prolapse, and also disclosed pulmonary infundibulum dilatation, massive adipose infiltration of the right ventricular free wall, patchy fibrosis and scattered myocardial inflammatory infiltrates in the left ventricle; these features are all consistent with arrhythmogenic right ventricular cardiomyopathy.

[Ventricular tachycardia secondary to myocardial contusion in an athlete: a clinical case report]. / Tachicardia ventricolare secondaria a contusione miocardica in atleta: descrizione di un caso clinico.

A 22-year-old athlete complained of palpitations shortly after a chest trauma during a basket competition. His electrocardiogram showed a ventricular tachycardia of 250 beats per minute, reverted to sinus rhythm with a chest thump. Standard electrocardiogram was normal. The following days he had an enzymatic pattern consistent with acute myocardial infarction, and the echocardiogram evidentiated an apical hypokinesia with a mural thrombosis. The patient recovered completely; and 15 days after the acute event, a coronary arteriography and ventriculography did not revealed any abnormality.