Genetics: The tyrosine kinase domain of the insulin receptor gene is normal in women with hyperinsulinaemia and polycystic ovary syndrome

The cause of hyperinsulinaemia in polycystic ovary syndrome(PCOS) is unknown, but two recent reports have implicated mutationsof the tyrosine kinase domain of the insulin receptor gene intwo patients. We have undertaken amplification of the insulinreceptor gene using the polymerase chain reaction and single-strandedconformational polymorphism analysis in 22 hyperinsulinaemicpatients with PCOS. Of these patients, 50% were polymorphicin exon 17 of the insulin receptor gene, but none of the alterationsin sequence has been associated with insulin resistance. Thegenomic sequences in exons 18-21 were normal in all patients.We conclude that mutations involving the tyrosine kinase domainof the insulin receptor gene are a rare cause of insulin resistancein the PCOS.     

The association of cortical dysplasia and anterior horn arthrogryposis: a case report

We describe a 21-year-old woman with neurogenic congenital contractures (arthrogryposis) of the lower limbs, normal intelligence, hyper-reflexia and partial epilepsy. MRI revealed bilateral opercular (perisylvian) cortical dysplasia with infolding of cerebral cortex, a focal neuroblast migrational disorder. This type of migrational disorder is known to have a prenatal onset after the 20th fetal week, whereas the anterior horn cell degeneration responsible of neurogenic arthrogryposis originates at 12–14 weeks of gestation. A prenatal viral infection along the neural axis during both these gestational periods or a genetic defect could be responsible for both lesions in this case.     

Noninvasive determination of local wavespeed and distensibility of the femoral artery by comb-excited Fourier velocity-encoded magnetic resonance imaging: Measurements on athletic and nonathletic human subjects

Summary The local distensibility of arteries is of interest because distensibility varies from artery to artery, may be altered by disease to different extents in different arteries, and may be modified by physiological or pharmacological means. Using magnetic resonance imaging (MRI) we have measured local arterial wavespeed in the femoral artery in healthy human subjects and calculated local arterial distensibility. We acquired 2-D coronal and sagittal MR phase contrast angiograms of the femoral artery. We used a novel imaging technique, comb-excited Fourier velocity-encoded MRI, to obtain simultaneous measurements of arterial blood velocity at two stations 14cm apart on the femoral artery. The separation of the two stations divided by the delay between the onset of forward flow at the two stations was used to calculate the wavespeed. The measurements were made on 16 healthy men (8 athletes, 8 non-athletes) in the age range 20–30 years, who were scanned with the use of ECG gating and an extremity coil in a 1.5 Tesla scanner (GE Medical Systems, Milwaukee, WI). By systematically altering the delay between the R-wave and data acquisition, a temporal resolution of 2–4ms was achieved. The onset of forward flow at each station was determined from a least-squares fit to the data for 30% of the maximum velocity during the cardiac cycle. Average femoral artery wavespeed was 7.7m/s ± 1.2 in the athletes and 11.5m/s ± 1.1 in the non-athletes (P < 0.001). The corresponding arterial distensibility values were 1.87 ± 0.86 × 10^–5kg^–1 s²m and 7.72 ± 1.63 × 10^–6kg^–1 s²m (P < 0.001). In most of the subjects there was transient flow reversal in the femoral artery immediately preceding the onset of forward flow. This helped in the identification of the onset of forward flow and hence the determination of arterial wavespeed.     

Treatment of antineutrophil cytoplasmic antibody associated vasculitis: a systematic review

Context  Immunosuppressive therapies for antineutrophil cytoplasmic antibody (ANCA)–associated vasculitis have greatly advanced patient survival but have turned ANCA-associated vasculitis (AAV) into chronic, relapsing disorders. Long-term treatment and disease-related morbidity are major threats. The last decade has seen a collaborative international effort to determine effective treatment. Objective  To analyze the reported evidence on AAV therapy in order to provide physicians with a rational approach for dealing with various clinical scenarios. Data Sources  We searched English-language articles on the medical treatment of AAV published between 1966 and March 2007 using MEDLINE. Articles from the reference lists of the most relevant articles retrieved were also analyzed. Study Selection  Studies of current available drug treatments or medical interventions for patients with AAV were included. Duplicate publications, case reports, and uncontrolled trials and series including fewer than 10 patients were excluded. Data Synthesis  We included 2 meta-analyses, 20 randomized controlled prospective trials, and 62 uncontrolled trials with more than 10 patients or observational studies. Outcome measures and treatment protocols were heterogeneous across trials. Cotrimoxazole can be used alone or in combination with corticosteroids to induce and maintain remission in cases of isolated upper respiratory tract involvement. To induce remission, methotrexate plus corticosteroids can be used instead of cyclophosphamide for patients with generalized, non–organ-threatening disease. When methotrexate is used as maintenance therapy, the likelihood of relapse is high and rigorous monitoring is mandatory. Pulse cyclophosphamide with corticosteroids can be used to induce remission in patients with generalized organ-threatening disease. The combination of azathioprine and daily prednisone is effective in maintaining remission. Plasma exchange is at present the best complement to immunosuppressants in advanced renal disease. In Churg-Strauss syndrome, treatment can be started with high doses of corticosteroids, tapering them when the clinical situation improves. In patients with a high risk of death, cyclophosphamide should be introduced. Conclusions  Although AAV therapies should be tailored to the patient's specific clinical situation, evidence for treatment of several disease states is lacking. There is a need for safer and more effective drugs.