Tyrosine hydroxylase deficiency in three Greek patients with a common ancestral mutation

We present the clinical, biochemical, and molecular findings of three Greek patients with tyrosine hydroxylase (TH) deficiency. All patients presented with a severe clinical phenotype characterized by prominent motor delay, infantile parkinsonism, oculogyric crises, and signs of autonomic dysfunction. Cerebrospinal fluid analysis disclosed reduced dopamine metabolites and normal pterins. Response to levodopa was favorable though not dramatic. All patients were homozygous for a previously reported mutation (p.L236P). SNP haplotype analysis was consistent with a common ancestral mutation, thus indicating a founder effect in Greek patients with TH deficiency. © 2010 Movement Disorder Society     

Homer2 and Homer3 interact with amyloid precursor protein and inhibit Abeta production

The study of Amyloid Precursor Protein (APP) processing has been the focus of considerable interest, since it leads to Aβ peptide generation, the main constituent of neuritic plaques found in brains of Alzheimer's disease patients. Therefore, the identification of novel APP binding partners that regulate Aβ peptide production represents a pharmaceutical target aiming at reducing Αβ pathology. In this study, we provide evidence that Homer2 and Homer3 but not Homer1 proteins interact specifically with APP. Their expression inhibits APP processing and reduces secretion of Aβ peptides. In addition, they decrease the levels of cell surface APP and inhibit maturation of APP and β-secretase (BACE1). The effects of Homer2 and Homer3 on APP trafficking to the cell surface and/or on APP and BACE1 maturation could be part of the mechanism by which the expression of these proteins leads to the significant reduction of Aβ peptide production.     

Sleep disorders and health-related quality of life in patients with interstitial lung disease

Background

Interstitial lung diseases (ILD) are chronic and restrictive lung diseases with poor survival and quality of life. The aim of this study was to investigate the frequency of sleep disorders in idiopathic pulmonary fibrosis (IPF) and sarcoidosis and to assess patients’ quality of life in relation to these disorders.

Methods

Forty patients, 19 with IPF, and 21 with sarcoidosis stage II/III were included. They were compared with 15 healthy subjects. All patients performed all-night polysomnography (PSG) and completed the Epworth, Berlin, and Stop-Bang questionnaires. In order to evaluate the quality of life, all patients completed the Short-Form 36 (SF-36) questionnaire.

Results

Of the IPF patients, 68% were diagnosed with mild obstructive sleep apnea (OSA), 5.2% with moderate to severe, 5.2% with severe OSA, and 21% with no OSA. Of patients with sarcoidosis, 52.4% were diagnosed with mild OSA and 4.8% with moderate severity OSA. The remaining 42.8% did not have OSA. The health-related quality of life in both patients with IPF and patients with sarcoidosis was impaired especially in the domains concerning physical health and the level of independence, compared to the control group.

Conclusions

In this sample of patients with IPF and sarcoidosis, obstructive sleep apnea is common at least in a mild degree of severity. The SF-36 questionnaire may be a useful tool for the evaluation of the quality of life in these patients.

     

Evidence of tachyphylaxis associated with salmeterol treatment of chronic obstructive pulmonary disease patients

Bronchodilator therapy is lifelong mandatory for chronic obstructive pulmonary disease patients. There is evidence of loss of bronchodilator effectiveness over time with beta2-agonists but not with anticholinergics. The aim of this study was to examine the development of tachyphylaxis to the long-acting beta2-agonist salmeterol using as a control therapeutic regimen the combination of ipratropium bromide and salbutamol sulphate. Fifty-six subjects participated in a 20-week, crossover randomised clinical trial. The parameters forced expiratory volume at 1 s (FEV1), peak expiratory flow rate (PEFR) and FEV1/forced vital capacity were measured via spirometry and the parameters triangle DeltaFEV1%pre, triangle DeltaPEFR%pre and triangle DeltaAUC(0-2 h) were calculated. FEV1 increased significantly after two weeks of treatment with the combination treatment but not with the salmeterol. The observed diminished increase could be attributed to the development of tolerance to the long acting beta2-agonist. Salmeterol seems to be an effective bronchodilator, however, its duration of action over time and its peak effect might be subject to tachyphylaxis.     

Colchicine treatment of liver fibrosis

BACKGROUND/AIMS: Because of its antifibrotic and anti-inflammatory effects, colchicine has been proposed as a treatment for liver disease. The results from clinical trials have however been inconsistent. The aim of the present study was to evaluate the effect of colchicine in the treatment of patients with hepatic fibrosis of various etiologies. METHODOLOGY: Thirty-eight patients were randomized to receive either colchicine 1 mg per day (n=21, group A) or no antifibrotic agent (n=17, group B). Treatment lasted for at least 12 months. Liver biopsy was performed prior to entry and after 12 months. Liver function tests, serum aminoterminal peptide of procollagen III (PIIINP) levels and CD4:CD8 ratio of peripheral blood T lymphocytes (PBTLs) were performed at baseline and bimonthly or every 4 months post-treatment. RESULTS: Mean albumin serum levels increased 12 months post-treatment period only in group A (p<0.05). Mean serum PIIINP levels did not change significantly after 12 months of treatment in group A; in 7 patients a reduction in mean serum PIIINP levels was noticed during 24-month post-treatment follow-up period (p<0.05). At baseline, a correlation between focal or bridging necrosis and CD4:CD8 ratio of PBTLs was noticed in group A (p < 0.05). The mean serum CD4:CD8 ratio was increased after 12 months of colchicine treatment (p<0.05) associated with abrogation of this correlation; comparison between the two groups revealed increased CD4:CD8 ratio in group A at 12 months (p<0.05). The histological findings according to Knodell criteria in both groups remained unchanged after 12 months follow-up. The treatment was well tolerated in all patients. CONCLUSIONS: Long-term colchicine treatment in patients with hepatic fibrosis appears to exert an anti-inflammatory, anti-fibrotic and immunomodulatory effect.     

Stability and antibacterial potency of ceftazidime and vancomycin eyedrops reconstituted in BSS® against Pseudomonas aeruginosa and Staphylococcus aureus

Purpose: We aimed to study the stability and the in vitro antibacterial potency of ceftazidime and vancomycin eyedrops against Pseudomonas aeruginosa and Staphylococcus aureus, respectively, under different storage temperatures and light conditions. Methods: Solutions of ceftazidime 50 mg/ml and vancomycin 50 mg/ml were prepared by reconstituting with balanced salt solution (BSS^®) and stored at 4 °C and at 24 °C with and without exposure to light. The minimum bactericidal concentrations against P. aeruginosa and S. aureus were measured to evaluate the antimicrobial potency over a 4‐week period. Changes in the pH values and physical characteristics of the solutions were recorded over the same period of time. Results: The antibacterial potency of ceftazidime decreased significantly from days 3 and 7 onwards at storage temperatures of 24 °C and 4 °C, respectively, but was not affected by light exposure. The pH value progressed from acidic to alkaline, peaking at day 3, in all solutions. The antibacterial potency of vancomycin remained stable during the 4‐week period, but its pH showed a slight progression from acidic to less acidic, in all solutions. Conclusions: Ceftazidime eyedrops in BSS^® appear to remain effective against P. aeruginosa for ≥ 7 days when stored at 4 °C, but were less effective when stored at 24 °C. Loss of antibacterial potency coincides with the appearance of visual and olfactory signs of degradation. The transient rise in pH at day 3 is a matter of possible concern, however, as it may affect patient tolerance. By contrast, vancomycin eyedrops in BSS^® can be safely used for ≥ 4 weeks, stored at either 4 °C or 24 °C.     

Papillomatosis of intra- and extrahepatic biliary tree: Successful treatment with liver transplantation.

Approximately 60 cases of biliary papillomatosis have been reported in the world literature, while only 6 cases have been reported to be treated with liver transplantation. This rare disease, which is characterized by relapsing episodes of obstructive jaundice and cholangitis that lead to secondary cirrhosis and death from sepsis or liver failure, it is also considered premalignant because of its frequent malignant transformation (25-50%). We present a case of a 43-year-old white man with papillomatosis of intra- and extrahepatic biliary tree who sought care for repeated episodes of obstructive jaundice and cholangitis. The diagnosis was suspected after endoscopic retrograde cholangiopancreatography and confirmed by liver and common bile duct biopsies. The patient underwent orthotopic liver transplantation with Roux-en-Y hepatico-jejunostomy to treat end-stage liver cirrhosis. Fifteen months' follow-up revealed a patient with normal graft function and with no clinically or laboratory findings of disease recurrence or cancer development.     

Neonatal screening for hypothyroidism in Greece

One year's experience in screening for congenital hypothyroidism in Greece is reported. Thyroidstimulating hormone (TSH) determination by a radioimmunoassay on dried blood spots was selected as the screening method. During the first year of screening 75,879 newborn infants were tested from Guthrie blood spots taken on the 5th day of life. Eighteen cases of primary congenital hypothyroidism with serum TSH levels over 100 IU/ml were detected, giving an incidence of 1:4200. One case had already been diagnosed clinically. Replacement treatment was started between the 22nd and the 50th days of life.