Idiopathic pulmonary arteriovenous malformations: clinical and imaging characteristics.

Pulmonary arteriovenous malformations (PAVMs) can cause stroke, brain abscess or life-threatening haemorrhage. Most PAVMs are associated with hereditary haemorrhagic telangiectasia (HHT). The aim of the present study was to describe the clinical presentation and treatment outcomes of those with idiopathic PAVMs, which has not previously been described in the literature. Patients with idiopathic PAVMs were identified at our HHT centre. Retrospective review of charts and imaging were performed. 20 patients were identified with idiopathic PAVMs. The most common symptoms reported were dyspnoea and migraines (50 and 30% of patients, respectively). Previous complications of PAVMs included haemoptysis (20%), stroke (20%) and brain abscess (5%). A total of 28 focal PAVMs were identified. Most patients (80%) had a solitary PAVM. 13 out of 28 PAVMs (46%) were located in the lower lobes. Most were simple and fistulous rather than complex and plexiform. Transcatheter embolotherapy was performed in 17 patients and was successful in improving oxygenation in all cases. The clinical manifestations and complications of idiopathic PAVMs are similar to those associated with HHT. Idiopathic PAVMs are anatomically similar to HHT-related PAVMs except for a greater number of solitary PAVMs and a lack of lower lobe predominance. Transcatheter embolotherapy is a safe and effective method for treating idiopathic PAVMs.

Bifluranol, a novel fluorinated bibenzyl anti-androgen, its chemistry and disposition in different animal species.

The synthesis of bifluranol, a new fluorinated bibenzyl anti-androgen, and of 3H-labelled bifluranol is described. The absorption, distribution and excretion of bifluranol has been studied in mouse, rat, ferret and dog; it is readily absorbed following oral administration, but blood concentrations of the drug are low due to hepatic uptake and biliary excretion. Enterohepatic re-circulation occurs, but the drug is excreted primarily in the faeces and only small amounts appear in urine. This pattern of disposition and excretion is similar to that reported elsewhere for the bibenzyl, hexoestrol, and for the stilbene, diethylstilboestrol.

The metabolism of bifluranol by rat, dog and ferret.

The synthesis of monohydroxy- and dihydroxy-bifluranol, and of glucuronide and sulphate conjugates of bifluranol are described. Bifluranol administered orally to rats, ferrets and dogs at a dosage of 50 to 200 microgram kg-1 is mostly excreted in the faeces as unchanged bifluranol and bifluranol monosulphate, disulphate and monoglucuronide. The bifluranol is well absorbed and is mostly excreted in the bile, as six different conjugates, including a glucuronide sulphate found in all 3 species, and a glucuronide phosphate found only in ferret and dog bile. Hydroxylation of the aromatic rings occurs in the rat, to an extent of about 8% of the dose, but was not detected in ferret or dog.

Effects of the duration of initial oral corticosteroid treatment on the recurrence of inflammation in Vogt-Koyanagi-Harada disease.

PURPOSE: To evaluate the effects of the duration of oral corticosteroid treatment on the recurrence of inflammation in Vogt-Koyanagi-Harada (VKH) disease. METHODS: Retrospective analysis of 35 VKH patients who received oral corticosteroid during the first attack of VKH with a minimum follow-up of 6 months. Patients were divided into two groups on the basis of the oral corticosteroid treatment duration of less than 6 months or 6 months or more. Kaplan-Meier survival and Cox-regression analyses were carried out to compare the recurrence rates of inflammation in the two groups. RESULTS: The mean age of onset was 42.5 years and the mean follow-up duration was 3.6 years. During the follow-up period, 10 (58.8%) of the 17 patients who received oral corticosteroid for less than 6 months compared with 2 (11.1%) of the 18 patients who had treatment for 6 months or more developed recurrence of inflammation (P=0.003). Cox-regression analysis showed that the duration of oral corticosteroid treatment for less than 6 months was the only significant risk factor for recurrence of VKH after adjustment for age, gender, and the initial dosage of oral corticosteroid treatment (adjusted odds ratio=8.8, P=0.008). Patients who received oral corticosteroid treatment for less than 6 months were also more likely to have one eye with visual acuity of 20/200 or worse (P=0.016). CONCLUSIONS: Early withdrawal of oral corticosteroid is associated with increased risk of recurrence of VKH and worse visual prognosis. Oral corticosteroid should be tapered off slowly and maintained for at least 6 months for the treatment of acute VKH.

Pulmonary arteriovenous malformation: a rare, treatable cause of stroke in young adults.

Pulmonary arteriovenous malformation (PAVM) predisposes affected patients to a significantly increased risk of stroke. Most commonly, PAVM is seen in patients with hereditary haemorrhagic telangiectasia (HHT), an inherited disorder that can be difficult to diagnose in young people because of variable age-related penetrance. As such, stroke in the young adult may be the presenting feature of underlying PAVM in a previously undiagnosed patient. The importance of considering this diagnosis in the evaluation of young adults with cryptogenic stroke is underscored by the availability of both sensitive screening and effective treatment for PAVM, from which this at-risk population can greatly benefit.

Studies of two novel sulfasalazine analogs, ipsalazide and balsalazide.

Sulfasalazine appears to exert its beneficial effect in colitis by releasing 5-aminosalicylic acid in the colon, but its use can be limited by side effects. Ipsalazide and balsalazide are novel sulfasalazine analogs designed to release 5-aminosalicylic acid and a nontoxic carrier molecule in the gastrointestinal tract. They have a low oral toxicity following single or repeat administration to mouse, rat, and ferret, and balsalazide is not mutagenic in the Ames test. Ipsalazide and balsalazide are split in rat and man, and the urinary and fecal excretion pattern of the 5-aminosalicylic acid released is similar to that of sulfasalazine; the carrier molecules are absorbed to a lesser extent than the sulfapyridine derived from sulfasalazine. These two analogs deserve therapeutic trial.