Quality of life in noncompliant adults with phenylketonuria after resumption of the diet.

BACKGROUND: Discontinuation of dietary therapy in adults with phenylketonuria can lead to neuropsychological abnormalities and emotional problems. The aim of our study was to assess the change in quality of life in adult patients returning to the diet and to define the reasons for failure in diet resumption. METHODS: Quality of life was assessed by means of the Psychological General Well-Being Index before study entry and subsequently after 3 and 9 months. Reasons for failure in diet resumption were analysed. RESULTS: 53 patients participated in the study. Initial quality of life assessment revealed severe distress in 17%, moderate distress in 28% and positive well-being in 55% of them. In the majority of patients with severe or moderate distress, improvement of subjective well-being was observed (especially in the domains of anxiety and depressiveness) if they managed to return to the diet (blood phenylalanine concentrations before study entry 0.78-1.62 mmol/L, mean 1.16 mmol/L; average blood phenylalanine concentration decrease by 0.42 mmol/L). Only 29 persons managed to maintain the diet for at least 3 months and only 10 participants finished the entire 9-month study protocol. Problems with dietary treatment while at work, the high cost of low-protein products and poor knowledge regarding proper diet were the most important factors responsible for failure in resumption of diet. CONCLUSION: Interpersonal differences exist between adult patients on relaxed diet, in some of whom quality of life often remains good, while others can suffer from severe emotional distress. Returning to diet increases quality of life in the majority of patients.

Serum markers of bone turnover in children and adolescents with classic galactosemia.

PURPOSE: Classic galactosemia is an inherited metabolic disease resulting from galactose-1-phosphate uridyltransferase (GALT) deficiency. Dietary lactose exclusion reverses many clinical manifestations of acute phase of the disease. Unfortunately most of the patients, despite dietary treatment, develop long-term complications among them disturbances of bone mineralization resulting in decrease of bone mineral density (BMD). The aim of our study was to assess bone formation and resorption processes with bone turnover markers in children and adolescents with galactosemia. MATERIALS AND METHODS: We studied 62 galactosemic children (mean age+/-SD 5.9+/-2.7 years) and adolescents (mean age+/-SD 15.6+/-2,4 years). The clinical diagnosis had been confirmed by the absence of GALT activity in erythrocytes. All patients were diagnosed in the neonatal period and had good dietary control. Healthy children (n=70) were the reference group. Serum osteocalcin (OC), bone alkaline phosphatase (BALP), collagen type I crosslinked C-telopeptide (CTX-I), 25(OH)D metabolite of vitamin D were determined by ELISA assays. RESULTS: We observed similar mean values of bone formation markers in children with galactosemia as compared to the age-matched controls. The level of bone resorption marker CTX-I in these patients was lower by about 20% (p<0.001) than in healthy children. On the contrary we obtained slightly higher values of CTX-I in adolescents with galactosemia in comparison to the age-matched controls. In these patients the values of OC and BALP were significantly higher than in healthy adolescents (111.8+/-52.1 microg/L versus 82.3+/-43.0 microg/L, p<0.02; and 95.4+/-45.7 U/L versus 72.6+/-40.6 U/L, p<0.05 respectively). CONCLUSION: Our results suggest that bone turnover in galactosemic patients elevates from childhood to adolescence, whereas in healthy individuals there is a decline during aging. Further studies on adults with galactosemia are necessary to assess bone status in these patients.

The response of patients with phenylketonuria and elevated serum phenylalanine to treatment with oral sapropterin dihydrochloride (6R-tetrahydrobiopterin): a phase II, multicentre, open-label, screening study.

This study aimed to evaluate the response to and safety of an 8-day course of sapropterin dihydrochloride (6R-tetrahydrobiopterin or 6R-BH4) 10 mg/kg per day in patients with phenylketonuria (PKU), who have elevated blood phenylalanine (Phe) levels, and to identify a suitable cohort of patients who would respond to sapropterin dihydrochloride treatment with a reduction in blood Phe level. Eligible patients were aged > or = 8 years, had blood Phe levels > or = 450 micromol/L and were not adhering to a Phe-restricted diet. Suitable patients were identified by a > or = 30% reduction in blood Phe level from baseline to day 8 following sapropterin dihydrochloride treatment. The proportion of patients who met these criteria was calculated for the overall population and by baseline Phe level (< 600, 600 to < 900, 900 to < 1200 and > or = 1200 micromol/L). In total, 485/490 patients completed the study and 20% (96/485) were identified as patients who would respond to sapropterin dihydrochloride. A reduction in Phe level was observed in all subgroups, although response was greater in patients with lower baseline Phe levels. Wide variability in response was seen across all baseline Phe subgroups. The majority of adverse events were mild and all resolved without complications. Sapropterin dihydrochloride was well tolerated and reduced blood Phe levels across all PKU phenotypes tested. Variability in reduction of Phe indicates that the response to sapropterin dihydrochloride cannot be predicted by baseline Phe level.

[Changes in the respiratory system as a sequela of drug adverse effects ]. / Zmiany w ukladzie oddechowym w nastepstwie niepozadanego dzialania leków.

In this review of the literature clinical aspects and pathogenic mechanisms of drug-induced pulmonary reactions are presented.

[Is it possible to predict the result of the bronchial provocation test in children with asthma?]. / Czy mozna przewidziec wynik testu prowokacyjnego oskrzeli u dzieci chorych na astme?

Bronchial hyperreactivity (BHR) to different allergic and non-allergic stimuli is characteristic feature of asthma. Sometimes however it is not possible to perform bronchial provocation test (BPT) assessing reactivity. It was interesting for us if the result of BPT can be predicted on the base of routine lung tests. The aim of the study is evaluation of the relationship between BPT results and baseline lung function tests assessing small bronchi obstruction in children suffering from asthma. Investigated group comprised 139 children aged 7 to 17 years, with episodic, mild or moderate asthma. During bronchial challenge lung function was assessed on the base of spirography and maximal flows at 50% and 25% of forced vital capacity (MEF50 and MEF25) and other indices as surface under end-half of flow-volume curve and mean flow times T50 and T25. The study results confirmed good correlation between BPT result and baseline lung function. Those children which had worse initial lung tests had more pronounced bronchial hyperreactivity. This relationship was the closest in the group of children with small bronchi obstruction. Analysis of correlation showed highly significant relationship between baseline lung function tests and degree of bronchial reactivity. The highest significance was observed for MEF50 and MEF25. We conclude that small bronchi test disturbances in children with asthma could predict with high probability results of bronchial challenge.

Internal organ involvement in juvenile connective tissue disease.

Using noninvasive investigative techniques, cardiac, pulmonary and gastrointestinal abnormalities were found in patients with all types of connective tissue diseases. Impedance rheography suggested impaired myocardial function. Abnormalities of pulmonary function included a decrease in diffusing lung capacity for CO (DL) values followed by restrictive ventilatory defects and mild alveolar hyperventilation. The results of endoscopic investigation of the gastrointestinal tract showed inflammatory changes. Ultrasonography revealed dyskinesis of the ducts of the gallbladder and some hepatic and pancreatic structural changes.

[Reactivity of the bronchi as a function of their initial state in children with asthma]. / Reaktywnosc oskrzeli jako funkcja ich stanu wyjsciowego u dzieci chorych na astme.

The aim of the study was to assess the effect of peripheral bronchial base-line status on the result of the bronchial provocation test. The study was carried out on a group of 65 children with bronchial asthma. Bronchial reactivity was assessed utilizing the carbachol provocation test. Higher reactivity was seen in children with initially lower indices of peripheral bronchial flow (MEF50, MEF25) (PC20 = 3,789 +/- 0.014 mg/ml) in comparison with children with normal indices (PC20 = 74,608 +/- 0,038 mg/ml) (p < 0.001). A linear correlation was found between the results of bronchial provocation (PC) and initial standardized small airway flow values (MEF50 - r = 0.56, p < 0.001; MEF25 - r = 0.49, p < 0.001). The correlation between bronchial provocation and initial FEV1/VC was weaker (r = 0.39 p < 0.01). The authors conclude that demonstration of decreased flow in peripheral, small airways utilizing MEF values enable to predict a positive result of bronchial provocation tests.