Late diagnosis of congenital adrenal hyperplasia due to 21-hydroxylase deficiency.

Congenital adrenal hyperplasia results from 21-hydroxylase deficiency in more than ninety percent of cases. The classical form of 21-hydroxylase deficiency presents in the neonatal period with virilization or adrenal insufficiency, with or without concurrent salt wasting. We report on a rare case of classic 21-hydroxylase deficiency diagnosed in late adulthood. A 39-year-old male patient presented for workup of infertility. Urologic investigation revealed small testes, bilateral testicular masses, and asthenozoospermia. The patient's steroid metabolism showed markedly increased levels of adrenal androgens, in particular of 17-hydroxyprogesterone amd 21-deoxycortisol. The gas chromatographic-mass spectrometric (GC-MS) urinary steroid profile was dominated by metabolites of 17-hydroxyprogesterone, while the endogenous glucocorticoid production was subnormally low. ACTH levels in plasma were elevated. These hormonal findings were consistent with 21-hydroxylase deficiency. Therapy with dexamethasone was initiated. The CTP21A2 gene analysis revealed the mutation I172N (ATC --> AAC) in exon 4 of allele 1 and a large gene deletion in allele 2. Cases of 21-hydroxylase deficiency diagnosed in late adulthood are rare; however, clinicians should be alert of this possibility.     

Long-term benefit to pallidal deep brain stimulation in a case of dystonia secondary to pantothenate kinase-associated neurodegeneration.

Pantothenate kinase-associated neurodegeneration (PKAN) is a rare autosomal recessive disorder with onset in childhood and rapid progression. There is no causative and insufficient symptomatic drug therapy. Deep brain stimulation (DBS) of the internal pallidum (GPi) has been reported to improve motor function. Most case reports, however, are limited to short observational periods. The impact of DBS on the progression and life expectancy in PKAN is unknown. We present a 5-year outcome and video documentation of bilateral GPi-DBS of an adolescent patient suffering from genetically defined PKAN.     

Short-term respiratory effects of cleaning exposures in female domestic cleaners.

Symptoms of obstructive lung disease in domestic cleaners have been related to the use of bleach and other irritant cleaning products. The short-term effects of cleaning exposures on respiratory symptoms and peak expiratory flow (PEF) were investigated in domestic cleaners with respiratory disorders. In a panel study, 43 female domestic cleaners with a recent history of asthma and/or chronic bronchitis completed a 2-week diary, collecting information on respiratory symptoms, PEF and cleaning exposures. Mixed regression models were used to assess daily changes in symptoms and PEF associated with specific cleaning exposures. The probability of having work-related asthma was individually assessed by a computerised diagnostic system and an occupational asthma expert. Lower respiratory tract symptoms were more common on working days and were predominantly associated with exposure to diluted bleach, degreasing sprays/atomisers and air fresheners. Associations with upper respiratory tract symptoms and PEF were less apparent. Eleven (30%) subjects scored positively for work-related asthma. It is concluded that exposure to certain irritant cleaning products aggravates lower respiratory tract symptoms in female domestic cleaners with asthma or chronic bronchitis.     

Thrombophilia and arterial disease. An up-to-date review of the literature for the vascular surgeon.

Thrombophilia may be defined as the tendency to arterial or venous thrombosis. Thrombophilia can be acquired or hereditary. Acquired conditions leading to arterial thrombosis are commonly encountered in vascular surgical practice, but less well known is the potential influence of genetic factors. In recent years, evidence has accumulated for a crucial role of genetic factors in the pathogenesis of venous thrombosis, many previously unknown genetic defects having been recently identified. The role of genetic predisposition for the pathogenesis of arterial occlusive disease on the other hand is unknown, although recent publications suggest a definite link. This may have implications for the vascular surgeon in the management of patients with arterial disease. A medline search was performed in order to identify papers published between 1990-2002 on thrombophilia, arterial disease and peripheral arterial occlusive disease (PAOD). With regard to venous thrombosis we obtained a much wider knowledge about genetic defects leading to thrombophilia. This has altered the diagnostic and therapeutic approach to patients with venous thrombosis, and has had an important influence on counselling and screening of family members, especially females of childbearing age. With regard to arterial thrombosis, certain thrombophilic disorders have a definite pathophysiological role. Hyperhomocysteinaemia, inherited or acquired, has been demonstrated to be an independent risk factor for athero-thrombosis. The antiphospholipid antibody syndrome (APS), an acquired condition, also predisposes to arterial thrombosis. Other thrombophilic conditions, such as prothrombin gene G20210A variant or factor V Leiden, have been investigated, but current evidence does not unequivocally support the hypothesis of a pathophysiological role in athero-thrombosis. Routine screening for thrombophilia in patients with athero-thrombosis is therefore not generally recommended on the basis of current evidence, but there is a role for selective screening.     

Multilevel surgery for obstructive sleep apnea: short-term results.

OBJECTIVE: To determine the efficacy of a new multilevel surgical protocol for obstructive sleep apnea (OSA). STUDY DESIGN AND SETTING: Sixty patients with moderate to severe OSA because of multilevel pharyngeal obstruction were enrolled into this prospective, controlled clinical trial after clinical examination, endoscopy, and polysomnography. Surgery included uvulaflap, tonsillectomy, hyoid suspension, and radiofrequency treatment of the tongue base (group A). A second group did not receive hyoid suspension (group B). In both groups, nasal surgery was performed if necessary. Polysomnography and Epworth Sleepines Scale (ESS) were recorded at baseline and 2 to 15 months after surgery. RESULTS: In group A, the mean apnea-hypopnea index (AHI) decreased significantly after surgery (38.9 +/- 20.0 vs 20.7 +/- 20.6, P < 0.0001), whereas in group B the AHI did not. All secondary variables (minimal oxygen saturation, mean oxygen saturation, arousal index), and the ESS significantly improved in group A with only changes in arousal index and ESS reaching levels of significance in group B. CONCLUSION: The presented protocol including the hyoid suspension proved to be effective in the treatment of OSA, whereas surgery without hyoid suspension was less successful. EBM rating: B-2b.     

News for the Practitioner

News for the Practitioner     

Structure-activity relationship between (E)-5-(2-bromovinyl)- and 5-vinyl-1-beta-D-arabinofuranosyluracil (BV-araU, V-araU) in inhibition of Epstein-Barr virus replication.

The structure-activity relationship between (E)-5-(2-bromovinyl)- and 5-vinyl-1-beta-D-arabinofuranosyluracil (BV-araU and V-araU) in inhibition of Epstein-Barr virus (EBV) was evaluated. Both V-araU and BV-araU effectively inhibited EBV replication in virus-producer P3HR-1(LS) cells, as determined by DNA-DNA hybridization. The 50% effective doses (ED50) for viral DNA replication were 0.005 and 0.3 microM for V-araU and BV-araU, respectively. The in vitro therapeutic index was 4000 for V-araU and 1300 for BV-araU. Synthesis of EBV-induced polypeptides with molecular weights of 145,000 (145, 140, 130, and 110 kDa) was significantly inhibited by both drugs. Only V-araU inhibited the synthesis of 85-, 55-, and 32-kDa polypeptides by approx. 50%. Kinetic analysis of inhibition and reversibility of EBV DNA replication after removal of the drugs indicated that BV-araU has a more prolonged inhibitory effect than V-araU. These results indicate that the substitution of H by Br in the 5-vinyl group results in marked reduction in anti-EBV activity while prolonging the drug effect and diminishing cytotoxicity.     

Follow-up of men with genital papilloma virus infection. Psychosexual aspects.

Genital papilloma virus infection (GPVI) is in many patients a longlasting, relapsing disease for which no effective treatment is available. This fact and the association between the virus and cancer puts much stress on the afflicted patient. Of 41 men with GPVI interviewed, 17 (40%) reported a negative effect of the disease on their sexual life. Most distressing was the fear of transmitting the disease to their partner. After 18 months, 15 (37%) of the 41 men still exhibited signs of GPVI. In the care of patients with GPVI, more attention needs to be paid to the psychosexual effects of the disease.