Clinical evaluation of a functional prothrombin time-based assay for identification of factor V Leiden carriers in a group of Italian patients with venous thrombosis.

The efficiency of a new prothrombin-based activated protein C (APC) resistance test to detect factor V Leiden (FVL) was clinically evaluated in 150 Italian patients with deep venous thrombosis. Patient samples are diluted in factor-V-deficient plasma, an APC-containing reagent, and specific factor V activator; after incubation, clotting is initiated by addition of activated-factor-FV-dependent prothrombin activator. Two prothrombin time determinations were performed under identical assay conditions except that no APC was added to one. A ratio over 4.2 for normal individuals and under 2.0 for FVL patients is expected: between 1.3 and 1.9 for FVL heterozygotes, and between 1.0 and 1.1 for FVL homozygotes. Using a predefined cut-off ratio of 2.0, a specificity and a sensitivity of 1.00 for detection of FVL mutation were found. With a cut-off ratio of 1.1, a specificity of 0.98 and a sensitivity of 1.00 were found for discrimination between FVL heterozygous (n = 60) and homozygous (n = 6). No interferences by heparins, oral contraceptives, oral anticoagulant therapy, protein C, protein S, D-dimer, homocysteine, MTHFR mutations and antiphospholipid autoantibodies were detected. In our experience, this new prothrombin time-based APC resistance assay provides improved discrimination between normal individuals and FVL carriers compared with the classical methods. Moreover, this new assay allows good discrimination between homozygous and heterozygous FVL carriers. In the authors' experience this prothrombin time-based method was not influenced by many factors compared with the classical activated partial thromboplastin time-based method.     

Benign intracranial hypertension and recombinant growth hormone therapy in Australia and New Zealand

Benign intracranial hypertension (BIH) is reported in three children from Australia and one from New Zealand, who were being treated with recombinant human growth hormone (rhGH). Three males and one female, aged between 10.5 and 14.2 y, developed intracranial hypertension within 2 weeks to 3 months of starting treatment. A national database, OZGROW, has been prospectively collecting data on all 3332 children treated with rhGH in Australia and New Zealand from January 1986 to 1996. The incidence of BIH in children treated with growth hormone (GH) is small, 1.2 per 1000 cases overall, but appears to be greater with biochemical GHD (<10IUml ^-1), i.e. 6.5/1000 (3 in 465 cases), relative risk 18.4, 95% confidence interval 1.9-176.1, than in all other children on the database. The incidence in patients with Turner's syndrome was 2.3/1000 (1 in 428 cases). No cases in patients with partial GHD (10–20 IUml ^-1) or chronic renal failure were identified. Possible causative mechanisms are discussed. The authors'practice is now to start GH replacement at less than the usual recommended dose of 14IUm-² week^-1 in those children considered to be at high risk of developing BIH. Ophthalmological evaluation is recommended for children before and during the first few months following commencement of rhGH therapy and is mandatory in the event of peripheral or facial oedema, persistent headaches, vomiting or visual symptoms. The absence of papilledema does not exclude the diagnosis.     

Extraperitoneal endometriosis: a diagnosis to be considered

Summary BACKGROUND: Endometriosis is a relatively common pathology in women of childbearing age and of low parity but rarely shows extraperitoneal involvement. The main aim of this paper is to raise the attention of specialists to the necessity of carrying out penetrating diagnosis of nonspecific extraperitoneal masses occurring in women of reproductive age. METHODS: We performed a retrospective review of six patients diagnosed with extraperitoneal endometriosis who were treated at the Vega Baja University Hospital (Spain) during the last 5 years. RESULTS: Surgical treatment had positive results in five patients. The preoperative diagnosis was correctly made in only two patients. The accurate aetiology of endometriosis remains unknown and diagnosis is based on clinical and cytopathological findings. CONCLUSIONS: Surgical treatment of extraperitoneal endometriosis is recommended. However, postoperative follow-up is obligatory and hormonal suppressive therapy may be necessary. Medical treatment with gestagens, Danazol, or agonists of the gonadotropin-releasing hormone are ineffective in endometriomas which are bigger than 2 cm.      

Carotid surgery. Is regional anesthesia always appropriate?

We retrospectively studied a series of 385 carotid endarterectomies performed either under general anesthesia (242) or under local anesthesia (145) to compare the peri-operative mortality and morbidity rate and to identify factors which may influence the choice of anesthesia. The rate of transient ischaemic attacks (TIA), stroke, death, combined mortality, severe neurological and cardiac morbidity were not statistically different. Under general anesthesia, more shunts were inserted (17% versus 7%, p less than 0.05) and more myocardial infarctions occurred (5% versus 0%, p less than 0.05). However, more strokes due to technical imperfection were seen under regional anesthesia. We concluded that regional anesthesia is more appropriate in patients with coronary artery disease and in patients at risk of intolerance to cross clamping. General anesthesia is more appropriate in poorly cooperative patients or in those with unfavorable operative conditions.     

Inhibition of morphine withdrawal by the association of RB 101, an inhibitor of enkephalin catabolism, and the CCKB antagonist PD-134,308.

1. The effects induced in rats on naloxone-precipitated morphine withdrawal syndrome by the new mixed inhibitor of enkephalin catabolism able to cross the blood-brain barrier RB 101 (N-((R,S)-2-benzyl-3[(S)(2-amino-4-methylthio)butyl dithio]-1-ox-opropyl-L-phenylalanine benzyl ester) given alone or associated with the selective CCKB antagonist, PD-134,308, were investigated. 2. The systemic administration of RB 101 (5, 10 and 20 mg kg-1, i.v.) elicited a significant decrease in 8 of the 14 withdrawal signs evaluated. PD-134,308 (3 mg kg-1, i.p.) did not modify the expression of morphine abstinence when given alone, but induced a strong facilitation of RB 101 responses (12 of 14 withdrawal signs were decreased). This potentiation was particularly intense in peripherally mediated withdrawal signs. 3. In order to clarify the biochemical mechanisms implicated in these responses, the effects induced by the association of RB 101 and PD-134,308 on the occupation of brain opioid receptors by endogenous enkephalins were also investigated in mice. PD-134,308, as well as RB 101, inhibited [3H]-diprenorphine binding to opioid receptors. These results suggest that an increase in endogenous enkephalin levels induced by PD-134,308 could participate in the facilitation of RB 101 behavioural responses. 4. RB 101 has a promising potential role in the management of the opiate withdrawal syndrome. CCKB antagonists, such as PD-134,308 may be useful in potentiating this anti-withdrawal effect.     

Dendritic spines in the visual cortex of the mouse: Introduction to a mathematical model

Summary The spines of apical dendrites of the layer V pyramidal cells of the area striata in the mouse represent a sequence of post-synaptic structures receiving a variety of contacts from terminal fibers derived fundamentally from short axon cells and superficial pyramidal cells. The study of Golgi preparations of mice 180 days old shows the existence of the most complicated terminal structures over portions of apical dendrites at the levels of layers III and IV. Observations on young mice reveals the terminations of the specific afferent fibers on the dendrites of short axon cells. A mathematical model which defines the distribution of spines along the apical dendrites is introduced. The principal equation of the model has been adjusted from the data processing of microscope countings through a series of programs written for an IBM 7070. The equation defines satisfactorily the different distributions of dendritic spines in mice 10–180 days old raised in normal conditions and in complete darkness. The equation defines also the distribution of dendritic spines in the visual cortex of mice enucleated at birth on one side, and the distribution along the apical dendrites of various cortical areas of the hamster, cat and man. The number of dendritic spines increases with the age of the subject and their distribution varies significantly according to the values of the parameters of the model.