Dietary practices in pyridoxine non-responsive homocystinuria: a European survey.

BACKGROUND: Within Europe, the management of pyridoxine (B6) non-responsive homocystinuria (HCU) may vary but there is limited knowledge about treatment practice. AIM: A comparison of dietetic management practices of patients with B6 non-responsive HCU in European centres. METHODS: A cross-sectional audit by questionnaire was completed by 29 inherited metabolic disorder (IMD) centres: (14 UK, 5 Germany, 3 Netherlands, 2 Switzerland, 2 Portugal, 1 France, 1 Norway, 1 Belgium). RESULTS: 181 patients (73% >16 years of age) with HCU were identified. The majority (66%; n=119) were on dietary treatment (1-10 years, 90%; 11-16 years, 82%; and >16 years, 58%) with or without betaine and 34% (n=62) were on betaine alone. The median natural protein intake (g/day) on diet only was, by age: 1-10 years, 12 g; 11-16 years, 11 g; and >16 years, 45 g. With diet and betaine, median natural protein intake (g/day) by age was: 1-10 years, 13 g; 11-16 years, 20 g; and >16 years, 38 g. Fifty-two percent (n=15) of centres allocated natural protein by calculating methionine rather than a protein exchange system. A methionine-free l-amino acid supplement was prescribed for 86% of diet treated patients. Fifty-two percent of centres recommended cystine supplements for low plasma concentrations. Target treatment concentrations for homocystine/homocysteine (free/total) and frequency of biochemical monitoring varied. CONCLUSION: In B6 non-responsive HCU the prescription of dietary restriction by IMD centres declined with age, potentially associated with poor adherence in older patients. Inconsistencies in biochemical monitoring and treatment indicate the need for international consensus guidelines.

Dietary management of urea cycle disorders: European practice.

BACKGROUND: There is no published data comparing dietary management of urea cycle disorders (UCD) in different countries. METHODS: Cross-sectional data from 41 European Inherited Metabolic Disorder (IMD) centres (17 UK, 6 France, 5 Germany, 4 Belgium, 4 Portugal, 2 Netherlands, 1 Denmark, 1 Italy, 1 Sweden) was collected by questionnaire describing management of patients with UCD on prescribed protein restricted diets. RESULTS: Data for 464 patients: N-acetylglutamate synthase (NAGS) deficiency, n=10; carbamoyl phosphate synthetase (CPS1) deficiency, n=29; ornithine transcarbamoylase (OTC) deficiency, n=214; citrullinaemia, n=108; argininosuccinic aciduria (ASA), n=80; arginase deficiency, n=23 was reported. The majority of patients (70%; n=327) were aged 0-16y and 30% (n=137) >16y. Prescribed median protein intake/kg body weight decreased with age with little variation between disorders. The UK tended to give more total protein than other European countries particularly in infancy. Supplements of essential amino acids (EAA) were prescribed for 38% [n=174] of the patients overall, but were given more commonly in arginase deficiency (74%), CPS (48%) and citrullinaemia (46%). Patients in Germany (64%), Portugal (67%) and Sweden (100%) were the most frequent users of EAA. Only 18% [n=84] of patients were prescribed tube feeds, most commonly for CPS (41%); and 21% [n=97] were prescribed oral energy supplements. CONCLUSIONS: Dietary treatment for UCD varies significantly between different conditions, and between and within European IMD centres. Further studies examining the outcome of treatment compared with the type of dietary therapy and nutritional support received are required.

Dietary management of urea cycle disorders: UK practice.

BACKGROUND: There is no published data describing UK dietary management of urea cycle disorders (UCD). The present study describes dietary practices in UK inherited metabolic disorder (IMD) centres. METHODS: Cross-sectional data from 16 IMD centres were collected by a questionnaire describing the management of UCD patients on prescribed protein-restricted diets. RESULTS: One hundred and seventy-five patients [N-acetylglutamate synthase deficiency, n = 3; carbamoyl phosphate synthase deficiency (CPS), n = 8; ornithine transcarbamoylase deficiency (OTC), n = 75; citrullinaemia, n = 41; argininosuccinic aciduria (ASA), n = 36; arginase deficiency, n = 12] were reported; 70% (n = 123) aged 0-16 years; 30% (n = 52) >16 years. Prescribed median protein intake decreased with age (0-6 months: 2 g kg(-1) day(-1); 7-12 months: 1.6 g kg(-1) day(-1); 1-10 years: 1.3 g kg(-1) day(-1); 11-16 years: 0.9 g kg(-1) day(-1) and >16 years: 0.8 g kg(-1) day(-1)) with little variation between disorders. Adult protein prescription ranged 0.4-1.2 g kg(-1) day(-1) (40-60 g day(-1)). In the previous 2 years, 30% (n = 53) were given essential amino acid supplements (EAAs) (CPS, n = 2; OTC, n = 20; citrullinaemia, n = 15; ASA, n = 7; arginase deficiency, n = 9). EAAs were prescribed for low plasma quantitative essential amino acids (n = 13 centres); inadequate natural protein intake (n = 11) and poor metabolic control (n = 9). From diagnosis, one centre prescribed EAAs for all patients and one centre for severe defects only. Only 3% (n = 6) were given branch chain amino acid supplements. Enteral feeding tubes were used by 25% (n = 44) for feeds and 3% (n = 6) for medications. Oral energy supplements were prescribed in 17% (n = 30) of cases. CONCLUSIONS: In the UK, protein restriction based on World Health Organization 'safe intakes of protein', is the principle dietary treatment for UCD. EAA supplements are prescribed mainly on clinical need. Multicentre collaborative research is required to define optimal dietary treatments.

Pretreatment nutritional status and locoregional failure of patients with head and neck cancer undergoing definitive concurrent chemoradiation therapy.

BACKGROUND: This study was carried out to determine if markers of nutritional status predict for locoregional failure following intensity-modulated radiation therapy (IMRT) with concurrent chemoradiotherapy (CCRT) for squamous cell carcinoma of the head and neck (SCCHN). METHODS: We performed a retrospective chart review of 78 patients with SCCHN who received definitive CCRT. We compared patient factors, tumor characteristics, and nutritional status indicators between patients with and without locoregional failure. RESULTS: Fifteen of 78 patients (19%) experienced locoregional failure. Median follow-up for live patients was 38 months. On univariate analysis, pretreatment percentage of ideal body weight (%IBW) (p < .01), pretreatment hemoglobin (p = .04), and treatment duration (p < .01) were significant predictors of failure. On multivariate analysis, pretreatment %IBW (p = .04) and treatment time (p < .01) remained statistically significant. CONCLUSIONS: Although treatment time is an accepted risk factor for failure, differences in outcome for patients with head and neck cancer undergoing definitive CCRT based on pretreatment %IBW should be examined further.

Photodynamic therapy for head and neck dysplasia and cancer.

OBJECTIVE: To determine the response of dysplasia, carcinoma in situ (CIS), and T1 carcinoma of the oral cavity and larynx to photodynamic therapy with porfimer sodium. DESIGN: Prospective trial. SETTING: A National Cancer Institute-designated cancer institute. PATIENTS: Patients with primary or recurrent moderate to severe oral or laryngeal dysplasia, CIS, or T1N0 carcinoma. INTERVENTION: Porfimer sodium, 2 mg/kg of body weight, was injected intravenously 48 hours before treatment. Light at 630 nm for photosensitizer activation was delivered from an argon laser or diode laser using lens or cylindrical diffuser fibers. The light dose was 50 J/cm(2) for dysplasia and CIS and 75 J/cm(2) for carcinoma. MAIN OUTCOME MEASURES: Response was evaluated at 1 week and at 1 month and then at 3-month intervals thereafter. Response options were complete (CR), partial (PR), and no (NR) response. Posttreatment biopsies were performed in all patients with persistent and recurrent visible lesions. RESULTS: Thirty patients were enrolled, and 26 were evaluable. Mean follow-up was 15 months (range, 7-52 months). Twenty-four patients had a CR, 1 had a PR, and 1 had NR. Three patients with oral dysplasia with an initial CR experienced recurrence in the treatment field. All the patients with NR, a PR, or recurrence after an initial CR underwent salvage treatment. Temporary morbidities included edema, pain, hoarseness, and skin phototoxicity. CONCLUSION: Photodynamic therapy with porfimer sodium is an effective treatment alternative, with no permanent sequelae, for oral and laryngeal dysplasia and early carcinoma. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00530088.

Chemoprevention of head and neck cancer with aspirin: a case-control study.

OBJECTIVE: To evaluate the chemopreventive potential of aspirin against head and neck cancer. DESIGN: Hospital-based case-control study. SETTING: National Cancer Institute-designated comprehensive cancer center. Patients Individuals who received medical services at the Roswell Park Cancer Institute, Buffalo, NY, between 1982 and 1998 and who completed a comprehensive epidemiologic questionnaire. MAIN OUTCOME MEASURE: Aspirin use among 529 patients with head and neck cancer and 529 hospital-based control subjects matched by age, sex, and smoking status. RESULTS: Aspirin use was associated with a 25% reduction in the risk of head and neck cancer (adjusted odds ratio, 0.75; 95% confidence interval, 0.58-0.96). Consistent risk reductions were also noted in association with frequent and prolonged aspirin use. Further, a consistently decreasing trend in risk was noted with increasing duration of aspirin use (P(trend) = .005). Risk reduction was observed across all 5 primary tumor sites, with cancers of the oral cavity and oropharynx exhibiting greater risk reduction. When analyzed by smoking and alcohol exposure levels, participants moderately exposed to either showed a statistically significant 33% risk reduction (adjusted odds ratio, 0.67; 95% confidence interval, 0.50-0.91), whereas participants exposed to both heavy smoking and alcohol use did not benefit from the protective effect of aspirin. The reduction in risk was relatively more significant in women. CONCLUSIONS: Aspirin use is associated with reduced risk of head and neck cancer. This effect is more pronounced in individuals with low to moderate exposure to cigarette smoke or alcohol consumption.

Predicting iron status in low birthweight infants.

OBJECTIVE: To determine the iron status of a selected group of low birthweight infants at approximately 9 months of age, and examine the feasibility of predicting iron status by examining the history of supplementary iron intake. METHODS: All live low birthweight infants recorded in the Dunedin Hospital Queen Mary Maternity Unit birth register who reached 9 months of age between November 1995 and September 1996 were eligible to participate. Infants were categorized into 'high' or 'low' iron intake groups depending on their consumption of infant formula or medicinal iron for one month prior to the study, and their iron status compared. RESULTS: Eighty-one infants of 73 mothers, with an average age of 10 months (range 8-13 months), participated. Thirty-three per cent (n = 27) were iron deficient: 19% (n = 15) had latent iron deficiency and 15% (n = 12) had iron deficiency anaemia. Those with a 'low' iron intake were 13-fold more likely to be iron deficient than infants with a 'high' iron intake (95% confidence interval: 4.4-41.5). Screening for iron deficiency using categories based on supplementary iron intake had a positive predictive value of 66% and a negative predictive value of 88%. CONCLUSIONS: The risk of iron deficiency was considerably greater for infants who had not received supplementary iron daily over the course of the previous month. Current preventative methods for avoiding poor iron status in this group of high risk infants are not effective. Screening for iron deficiency in low birthweight infants on the basis of iron intake from infant formula or medicinal iron provides a useful method for identifying infants whose iron status should be investigated.

Hyperbaric oxygen and neutrophil accumulation/tissue damage during permanent focal cerebral ischaemia in rats.

The use of hyperbaric oxygenation (HBO) for the treatment of severe brain ischaemia remains controversial. The HBO may interfere with destructive neutrophil (PMN) infiltration following ischaemia/reperfusion. The effects of HBO on PMN accumulation and the area of ischaemic tissue damage were investigated in rats having permanent focal ischaemia (4 h). The right middle cerebral arteries of a group of Wistar rats were permanently occluded. The rats were then randomly divided into those ( n=7) to be treated with HBO at 2 atm for 230 min and those ( n=8) to breathe air at atmospheric pressure for an equivalent period. The HBO had no effect on permanent ischaemia, as there was no significant difference in the area of ischaemic tissue damage between HBO-treated [mean (SD)] [331 (88) mm(3)] and non-treated animals [322 (111) mm(3)]. Moreover, the increase in myeloperoxidase [5.4 (4.1) compared to 2.4 (1.2) pg x g(-1) wet weight of brain] was not significantly different. The results indicate that HBO did not reduce tissue damage during 4 h of permanent focal ischaemia.