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.     

Assessment of cutaneous sensory and autonomic axon reflexes in rheumatoid arthritis.

OBJECTIVE--To assess sensory function in skin overlying the joints of patients with rheumatoid arthritis, in relation to the pain and tenderness which commonly arises in structures not directly involved in the inflammatory process. METHODS--An intradermal injection of capsaicin 0.05 microgram in 10 microliters was made over the wrists and forearms of 40 patients with rheumatoid arthritis and 46 control subjects. Axon reflex vasodilatation was measured using laser Doppler flowmetry. Cholinergic sympathetic function was assessed by measuring axon reflex sweating induced by a single intradermal injection of nicotine 0.5 microgram in 0.1 ml. RESULTS--Capsaicin induced axon reflex vasodilation over the wrists was found to decrease with age in normal subjects (r = -0.62, p < 0.001). In patients with rheumatoid arthritis, capsaicin induced axon reflex vasodilatation was significantly greater over the wrists, but not the forearms, when compared with age matched normal controls (p < 0.01). A minimal correlation between axon reflex vasodilatation and visual analogue pain score was apparent in the rheumatoid group (r = -0.37, p < 0.05). Nicotine induced sweating responses were similar in the rheumatoid and normal groups, and both showed a linear age related decline. CONCLUSIONS--The results show a selective increase of capsaicin induced vasodilatation in skin overlying joints in patients with rheumatoid arthritis. This suggests that the activity of a sub-population of periarticular small sensory fibres is altered, which may explain, at least in part, some of the clinical findings in this disorder.     

O,O′-二烷基-O″-(5-取代-3-苯并噻吩乙腈肟)磷酸酯及硫代磷酸酯的合成

合成了18个O,O′-二烷基-O″-(5-取代-3-苯并噻吩乙腈肟)磷酸酯及硫代磷酸酯类化合物(Ⅰ_1～18)。初步杀螺试验结果表明,其中5个化合物,即Ⅰ_2,3,7,11,12有明显的杀螺增效作用。     

Prolonged survival of nonhuman primate renal allograft recipients treated only with anti-CD4 monoclonal antibody

The immunosuppressive efficacy of the monoclonal antibody OKT4A reactive with human and monkey CD4 cells was evaluated in cynomolgus renal allograft recipients. Low-dose (0.1 to 0.3 mg/kg/day) intact monoclonal antibodies (10 recipients) or F(ab')2 fragments (two recipients) were administered for 12 days. High-dose OKT4A (10 mg/kg) was administered on the day of transplantation as the only suppression in five animals. Four control animals received either no therapy or a monoclonal antibody nonreactive with monkey cells (OKT3). Maximum survival of the control animals and those treated with F(ab')2 was 11 days. Mean survival in the recipients of low-dose OKT4A was 25.4 +/- 4.3 days and in the group receiving high-dose OKT4A it was 39 +/- 6.4 days. All OKT4A-treated animals showed "coating" and CD4 modulation without depletion of circulating T cells. No modulation occurred in the F(ab')2-treated recipients. Serial allograft biopsy specimens showed reduced lymphocyte infiltration that was nearly complete in recipients of high-dose OKT4A. Biopsy-derived donor-reactive cytotoxic T-cell lines were generated regularly from recipients of low-dose, but not high-dose, OKT4A during periods of stable function. All animals treated with monoclonal antibodies developed an immunoglobulin G antimurine humoral response. Thus OKT4A is a potent immunosuppressive agent administered even as a single bolus, and depletion of CD4 cells is not required to suppress rejection. Anti-CD4 monoclonal antibodies may prove useful in patients, perhaps requiring only a limited number of higher-dose injections in the peritransplant period.     

Another Advanced Test of Theory of Mind: Evidence from Very High Functioning Adults with Autism or Asperger Syndrome

Previous studies have found a subgroup of people with autism or Asperger Syndrome who pass second-order tests of theory of mind. However, such tests have a ceiling in developmental terms corresponding to a mental age of about 6 years. It is therefore impossible to say if such individuals are intact or impaired in their theory of mind skills. We report the performance of very high functioning adults with autism or Asperger Syndrome on an adult test of theory of mind ability. The task involved inferring the mental state of a person just from the information in photographs of a person's eyes. Relative to age-matched normal controls and a clinical control group (adults with Tourette Syndrome), the group with autism and Asperger Syndrome were significantly impaired on this task. The autism and Asperger Syndrome sample was also impaired on Happe's strange stories tasks. In contrast, they were unimpaired on two control tasks: recognising gender from the eye region of the face, and recognising basic emotions from the whole face. This provides evidence for subtle mindreading deficits in very high functioning individuals on the autistic continuum.     

Sera from patients with heparin-induced thrombocytopenia generate platelet-derived microparticles with procoagulant activity: an explanation for the thrombotic complications of heparin-induced thrombocytopenia

Heparin-induced thrombocytopenia is characterized by moderate thrombocytopenia and thrombotic complications, whereas quinine/quinidine-induced thrombocytopenia usually presents with severe thrombocytopenia and bleeding. Using flow cytometry and assays of procoagulant activity, we investigated whether sera from patients with these immune drug reactions could stimulate normal platelets to generate platelet-derived microparticles with procoagulant activity. Sera or purified IgG from patients with heparin-induced thrombocytopenia stimulated the formation of platelet-derived microparticles in a heparin-dependent fashion. Further studies showed that heparin-induced thrombocytopenia sera also produced a marked increase in procoagulant activity. In contrast, sera from patients with quinine- or quinidine-induced thrombocytopenia did not generate platelet-derived microparticles nor generate increased procoagulant activity. However, quinine/quinidine-induced thrombocytopenia sera produced a significant increase in the binding of IgG to platelets in a drug-dependent fashion, whereas sera from patients with heparin-induced thrombocytopenia demonstrated no drug-dependent binding of IgG to platelets. We also observed increased levels of circulating microparticles in patients with acute heparin-induced thrombocytopenia compared with control patients. Our observations indicate that the generation of procoagulant platelet-derived microparticles in vivo is a plausible explanation for the thrombotic complications observed in some patients with heparin-induced thrombocytopenia.