Hereditary Bleeding Disorder due to a Primary Defect in Platelet Release Reaction

S ummary . A large family with a hereditary bleeding disorder was investigated. Easy bruising, epistaxis and menorrhagia were noted in seven members of three generations and at least one member in each generation was affected. Platelet function abnormalities were characterized by reduced ¹⁴C-serotonin release, absent second wave aggregation in response to ADP or epinephrine and reduced aggregation in response to collagen. Bleeding time was prolonged in three individuals and platelet factor 3 availability was abnormal in four. Platelet count, morphology, adhesiveness and clot retraction were normal in all. Platelet ADP and ATP as well as ATP to ADP ratio were normal. This family probably represents the first documented instance of hereditary platelet primary release disorder. To elucidate the pathogenetic mechanism, further functional studies were performed. No appreciable shape change, ¹⁴C-serotonin release of aggregation was observed when the propositus' platelets were stimulated with sodium arachidonate or a PGH₂ analogue. By contrast, platelets responded normally to ionophore A23187, thrombin and ristocetin. The findings indicate that the hereditary primary release disorder is probably due to a reduced thromboxane A2 production secondary to thromboxane synthetase deficiency. Alternatively, it may be due to platelet membrane abnormalities which render platelets unresponsive to thromboxane A₂.     

Circular mapping and ablation of the pulmonary vein for treatment of atrial fibrillation: impact of different catheter technologies

OBJECTIVES: We conducted this study to compare the efficacy and safety of different catheter ablation technologies and of distal versus ostial pulmonary veins (PV) isolation using the circular mapping technique. BACKGROUND: Electrical isolation of the PVs in patients with atrial fibrillation (AF) remains a technical challenge. METHODS: Two hundred eleven patients (163 men; mean age 53 +/- 11 years) with symptomatic AF were included in this study. In the first 21 patients (group 1), distal isolation (> or = 5 mm from the ostium) was achieved targeting veins triggering AF. In the remaining 190 patients (group 2), ostial isolation of all PVs was performed using 4-mm tip (47 patients), 8-mm tip (21 patients), or cooled-tip (122 patients) ablation catheters. RESULTS: Distal isolation was able to eliminate premature atrial contractions (PACs) and AF in six of 21 patients (29%) and 10 of 34 PVs. After a mean follow-up time of 6 +/- 4 months, no patients treated with the 8-mm tip catheter experienced recurrence of AF, whereas 21% (10 of 47 patients) and 15% (18 of 122 patients) of the patients ablated with the 4-mm tip and the cooled-tip ablation catheters experienced recurrence of AF after a mean follow-up of 10 +/- 3 and 4 +/- 2 months, respectively. Significant complications including stroke, tamponade, and severe stenosis occurred in 3.5% (8/211) of patients. CONCLUSIONS: Catheter technologies designed to achieve better lesion size appeared to have a positive impact on procedure time, fluoroscopy time, number of lesions, and overall efficacy. Although distal isolation can be achieved with fewer lesions, ostial isolation is required in the majority of patients to eliminate arrhythmogenic PACs and AF.     

Bedside diagnostic laparoscopy for critically ill patients: a retrospective study of 62 patients

Background

Bedside diagnostic laparoscopy has an important role of diagnosing acute abdomen in critically ill patients hospitalized in the intensive care unit (ICU). Delayed diagnosis of intraabdominal pathology increases the morbidity and mortality rates for these patients, whose clinical signs often are absent due to analgesic medication and sedation.

Methods

In this retrospective study performed from January 2007 to December 2009, 62 consecutive ICU patients whose blood test results showed them to be hemodynamically unstable underwent bedside diagnostic laparoscopy. The inclusion criteria specified clinically suspected acute cholecystitis, unknown sepsis, acidosis with a high level of lactate, elevated lab tests (white blood cell count, bilirubin, lactic dehydrogenase, creatine phosphokinase, gamma glutamyl transferase [??GT]), and acute anemia with suspected intraabdominal bleeding. The major contraindications to bedside diagnostic laparoscopy were coagulopathy, endocranic hypertension, and heart failure. Patients with a clear indication for an open surgical procedure were excluded from the study.

Results

Of the 62 patients who underwent bedside diagnostic laparoscopy, 43 (69.3?%) had positive findings and 29 (46.7?%) had acute acalculous cholecystitis. The mean operation time was 38 min, and no procedure-related deaths occurred. The procedure was performed for postsurgery patients, especially after cardiac operations, and for trauma or septic patients. Respiratory and hemodynamic parameters were monitored before, during, and after the procedure.

Conclusions

As a minimally invasive procedure, bedside diagnostic laparoscopy can be performed in the ICU for hemodynamically unstable patients. It is safe procedure with high diagnostic accuracy for acute intraabdominal conditions that avoids negative laparotomies for unstable patients. The bedside diagnostic laparoscopy procedure is not performed widely, and prospective studies are needed to better evaluate outcome and advantages for critically ill patients.     

Severe head injury in early infancy: analysis of causes and possible predictive factors for outcome

Object The aim of this study was to analyse the causes and prognostic factors for outcome in severe traumatic brain injuries (TBI) in early infancy. Materials and methods We present a retrospective study on 16 infants aged less than 12 months observed over the last 20 years in our department for severe brain injury. Infants were evaluated by the Children Coma Scale (CCS). We assessed Glasgow Outcome Scale (GOS) at discharge and at 12 months after discharge. Conclusions The main causes of trauma were domestic accidents followed by car accidents. The highest positive correlation was found between the GOS score at 1 year and the presence of hypoxia and hypotension at admission, the presence of hyperglycaemia at 24 h and the occurrence of major clotting disorders. A significant but weaker correlation was found with the CCS at admission, the occurrence of early post-traumatic seizures and the length of stay in the intensive care unit.     

Basophil activation in idiopathic mixed cryoglobulinemia

We studied basophil activation in patients affected by idiopathic mixed cryoglobulinemia in order to investigate the role of the basophil cell in the pathogenesis of the vasculitis typical of this disease. We selected 13 patients and we performed thein vitro basophil degranulation test with cryoprecipitate; in 5 cases the test was positive when it was performed in whole blood, while it was negative when it was performed with cells washed and resuspended in Tyrode's buffer. In 6 subjects it was not possible to perform the test because of the very low number of circulating basophil cells. Finally, in 2 subjects thein vitro basophil degranulation test with cryoprecipitate was negative; this result may be related to the very low levels of complement factors in the sera of these subjects. These findings sugges that the pathogenetic mechanism of vasculitis in idiopathic mixed cryoglobulinemia could be started by basophil activation.     

Serotonin involvement in the basal ganglia pathophysiology: could the 5-HT2C receptor be a new target for therapeutic strategies?

The basal ganglia are a highly interconnected group of subcortical nuclei in the vertebrate brain that play a critical role not only in the control of movements but also in some cognitive and behavioral functions. Several recent studies have emphasized that serotonergic pathways in the central nervous system (CNS) are intimately involved in the modulation of the basal ganglia and in the pathophysiology of human involuntary movement disorders. These observations are supported by anatomical evidence demonstrating large serotonergic innervation of the basal ganglia. In fact, serotonergic terminals have been reported to make synaptic contacts with dopamine (DA)-containing neurons and gamma-aminobutyric acid (GABA)-containing neurons in the striatum, globus pallidus, subthalamus and substantia nigra. These brain areas contain the highest concentration of serotonin (5-HT), with the substantia nigra pars reticulata receiving the greatest input. Furthermore, in these structures a high expression of 5-HT different receptor subtypes has been revealed. In this paper, evidence demonstrating the serotonergic control of basal ganglia functions will be reviewed, focusing on the role of the 5-HT2C receptor subtype. In addition, the involvement of 5-HT2C receptors in neurological disorders such as Parkinson's disease and other related motor disorders, and their management with drugs blocking the 5-HT2C receptor will be discussed.     

Contrasting performance of right- and left-hemisphere patients on short-term and long-term sequential visual memory

Fifty control subjects and 100 patients with damage restricted to one hemisphere were given two memory tests, one requiring immediate recognition of increasingly longer sequences of pictures and the second learning to criterion the order of presentation of eight pictures.On the short-term memory test, left- but not right-brain-damaged patients scored significantly lower than controls. Their inferiority disappeared when the means were corrected for Token Test scores. On the learning test, right-brain-damaged patients performed more poorly than controls and failed to reach criterion in a significantly higher proportion than left-brain-damaged patients. When the standardized scores on the two tests were compared, the left hemisphere group was found to perform more poorly on the short-term than on the long-term memory test, while the right-brain-damaged group showed the opposite pattern. It was concluded that the aid provided by the verbal code in sequential memory for pictures is limited to conditions requiring brief storage, while long-lasting acquisition of a pictorial sequence is mainly mediated by visual images.     

Central serotonin2C receptor: from physiology to pathology

Since the 1950s, when serotonin (5-HT) was discovered in the mammalian central nervous system (CNS), an enormous amount of experimental evidence has revealed the pivotal role of this biogenic amine in a number of cognitive and behavioural functions. Although 5-HT is synthesized by a small group of neurons within the raphe nuclei of the brain stem, almost all parts of the CNS receive serotonergic projections. Furthermore, the importance of 5-HT modulation and the fine-tuning of its action is underlined by the large number of 5-HT binding sites found in the CNS. Hitherto, up to 15 different 5-HT receptors subtypes have been identified. This review was undertaken to summarize the work that has explored the pathophysiological role of one of these receptors, the 5-HT2C receptor, that has been emerged as a prominent central serotonin receptor subtype. The physiology, pharmacology and anatomical distribution of the 5-HT2C receptors in the CNS will be firstly reviewed. Finally, their potential involvement in the pathophysiology of depression, schizophrenia, Parkinson's disease and drug abuse will be also discussed.