The use of recombinant-activated factor VII in von Willebrand disease: a case series.

Spontaneous and surgery-associated bleeding in patients with von Willebrand disease (vWD) cannot always be controlled with desmopressin or replacement therapy. This paper presents results on the use of recombinant-activated factor VII (rFVIIa) in patients with vWD included in the internet registry Haemostasis.com. Twenty-eight reports on the use of rFVIIa in vWD were identified from the database and included in this analysis. The bleeding episodes were classified as mild (n = 7), moderate (n = 16), or severe (n = 2), and were unspecified in three cases. The median dose of rFVIIa administered was 94 microg/kg body weight (40-127.3 microg/kg). Bleeding stopped in 23 of 27 evaluable patients (85%) and markedly decreased in three patients; the total response rate was 96% (26/27 patients). Response did not correlate with the type of vWD, the site or severity of the initial bleed, or the rFVIIa dose. Other replacement therapies were infrequently used, and their use was similar in the 24 h before and after rFVIIa administration. Eighteen patients also received antifibrinolytic treatment, but its impact on response was not recorded. Only one adverse event (mild fever) was observed. These cases suggest a role for rFVIIa as a safe and effective therapy for vWD.     

Lactation-induced plasticity in the supraoptic nucleus augments axodendritic and axosomatic GABAergic and glutamatergic synapses: an ultrastructural analysis using the disector method

The disector, an unbiased stereological method for evaluation of synaptic densities, was used to analyse putative GABA and glutamate innervations of the supraoptic nucleus of virgin and lactating rats. The analysis was performed on ultrathin sections labelled for either of the amino acids with a postembedding immunogold technique. Our observations showed that the volume of the nucleus increased by 40% in lactating animals, an increase due to a significant enlargment of dendritic and somatic, but not vascular, volumes. Nevertheless, values of overall synaptic densities in the whole nucleus remained as high as those in virgin rats (37–40×10⁶ synapses/mm³). About 45% of all synapses were immunoreactive for GABA and 25% for glutamate; there were twice as many GABA- and glutamate-positive synapses on dendrites as on somata. When we estimated synaptic densities in relation to the neuropil (by subtracting the proportion of sampled areas occupied by somatic profiles), we found a significant increase in synaptic density in lactating animals. This affected axodendritic as well as axosomatic synapses, immunopositive and immunonegative for GABA or glutamate. The disector also allowed us to determine that the number of synapses from terminals making contacts on several somata and/or dendrites simultaneously constituted about 9% of all synapses in virgin rats, a proportion which more than doubled in lactating rats. About 50% were immunopositive for GABA and 30% for glutamate.

Our data offer further evidence of physiologically-linked structural synaptic plasticity in the supraoptic nucleus and clearly demonstrate that it affects both inhibitory and excitatory inputs on dendrites, as well as on somata, throughout the nucleus.     

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.     

Primary intraorbital meningioma and schwannoma--a rare association

Primary intraorbital meningioma and Schwannoma are rare tumours. For them to occur concurrently, or one following soon after another should be considered a curiosity. We present a 40 year old male who reported with proptosis of the right eye and a meningioma was removed surgically. Within 3 months symptoms recurred and a schwannoma was removed at surgery from the same site. Interesting features of the lesion are presented and discussed.     

Enterohepatic circulation of T-2 toxin metabolites in the rat

The enterohepatic circulation of T-2 toxin and its conjugated metabolites was examined in bile duct-cannulated male rats. Rats administered tritiated T-2 toxin intraduodenally (id) eliminated 44.65% and 57.25% of the administered dose in the bile within 4 and 8 hr post-dosing, respectively. TLC profiles of the T-2 metabolites were similar after intravascular and id administration. The major metabolites detected were 3'-OH-hydroxytryptamine-2 (HT-2), glucuronic acid conjugates, T-2 tetraol (TOL), 4-deacetylneosolaniol (4-DN), and HT-2. Tritium-labeled glucuronides obtained from the bile of rats administered [3H]T-2 toxin intravascularly were extracted and purified using C-18 and silica column chromatography. Enzymatic hydrolysis followed by TLC and GC/MS indicated that the aglycone portion of the glucuronides were composed of 3'-OH HT-2, HT-2, 4-DN, and TOL. After id administration of the glucuronides the rats eliminated 6.01% (4 hr) and 11.86% (8 hr) of the dose in the bile. No free metabolites of T-2 toxin were detected in the bile of any animals administered the purified glucuronides. Oral treatment of the rats with the beta-glucuronidase inhibitor, saccharolactone, did not produce a significant decline in the amount of radioactivity recovered in the bile following administration of the tritium-labeled glucuronides. These studies substantiate the enterohepatic circulation of T-2 toxin metabolites.