Vitamin D status and muscle function in children with neurofibromatosis type 1 (NF1).

OBJECTIVES: The aim of this cross-sectional study was to assess the vitamin D status and muscle function in children with NF1 compared with their unaffected siblings. METHODS: NF1 children between 5 and 18 years of age and who had at least one unaffected sibling were identified. Serum concentrations of 25-hydroxyvitamin D (25(OH)D), calcium, inorganic phosphate, alkaline phosphate, parathyroid hormone and 1,25-dihydroxyvitamin D were measured. The Leonardo Mechanography Ground Reaction Force Platform (GRFP) was used to measure EFI, jump power, force and height. RESULTS: There was no significant difference in 25(OH)D between NF1 subjects and unaffected siblings. Relative jump power and force were found to be significantly different. The adjusted means (95% confidence limits) of non-NF1 and NF1 children for relative jump power (W/kg), controlling for body mass and age, were 37.31 (34.14, 40.49) and 32.51 (29.34, 35.68), respectively (P=0.054); and force (N/kg), controlling for body mass, age and gender, were 25.79 (24.28, 27.30) and 21.12 (19.61, 22.63), respectively (P<0.0001). Jumping parameters were not related to serum 25(OH)D. CONCLUSIONS: There was no significant relationship between vitamin D status and NF1 status in children. NF1 children had significantly impaired jumping power and force, when compared to their unaffected siblings.

Treatment and secondary prevention effects of the probiotics Lactobacillus paracasei or Bifidobacterium lactis on early infant eczema: randomized controlled trial with follow-up until age 3 years.

BACKGROUND: Allergic disease has been associated with altered intestinal microbiota. Therefore, probiotics have been suggested as a potential treatment for eczema. OBJECTIVE: We investigated whether dietary supplementation of infants with eczema at age 3-6 months with Lactobacillus paracasei CNCM I-2116 or Bifidobacterium lactis CNCM I-3446 had a treatment effect or altered allergic disease progression. METHODS: Primary outcome included eczema severity (SCORing Atopic Dermatitis, SCORAD) 3 months post-randomization. Secondary: SCORAD (other visits); infant dermatitis quality of life (IDQoL); gastrointestinal permeability; urinary eosinophilic protein X; allergen-sensitization; allergic symptoms (age 12, 18, 36 months). A total of 208 infants aged 3-6 months with physician-diagnosed eczema were recruited; 137/208 (SCORAD ≥ 10, consuming ≥ 200 mL standard formula/day) were randomized to daily supplements containing L. paracasei or B. lactis or placebo for a 3-month period, while receiving extensively hydrolysed whey-formula (dairy-free diet). There were two open observational groups, one group exclusively breastfed (n = 22) and the other, standard formula-fed (n = 49). TRIAL NUMBER: ISRCTN41490500. RESULTS: Eczema severity decreased significantly over time in all groups. No significant difference was observed between randomized groups after 12-week treatment-period (SCORAD-score pre-/post-intervention: B. lactis 25.9 [95% CI: 22.8-29.2] to 12.8 [9.4-16.6]; L. paracasei 25.4 [22.1-29] to 12.5 [9.2-16.4]; placebo 26.9 [23.4-30.6] to 11.8 [9.6-14.3]; P = 0.7). Results were similar when analysis was controlled for allergen-sensitization, or when only sensitized infants were analysed. No differences were found for secondary outcomes. No difference was observed in SCORAD-score between randomized and observational groups. CONCLUSION AND CLINICAL RELEVANCE: We found no benefit from supplementation with B. lactis or L. paracasei in the treatment of eczema, when given as an adjunct to basic topical treatment, and no effect on the progression of allergic disease from age 1 to 3 years.

Ethics in nursing: the way forward.

This series of articles has been developed with the intention of increasing nurses' awareness of ethics and ethical decision-making and clarifying the relationship between ethical thinking and effective nursing practice. A number of issues have been examined to show how ethics affects the professional role, but many other clinical and non-clinical aspects of nursing demand ethical exploration. In the final article in the series, the relevance of ethics to effective nursing is emphasised and suggestions for enhancing the integration of ethical decision-making into practice are made.

Euthanasia: the legal issues.

The legal status of euthanasia is frequently deliberated. It remains unlawful in Britain and advocates for a change in the law are vigorously opposed by those who argue that it should remain unchanged. An objective account, in which current law and arguments for and against change are exposed, is essential to inform the euthanasia debate. In this article the legal issues concerning euthanasia are examined and arguments raised by proposed changes in the law are considered.

Voluntary euthanasia: ethical concepts and definitions.

Euthanasia is a highly emotive and contentious subject, giving rise to a great deal of debate. However, despite its frequent exposure in public and professional media, there appears to be a lack of clarity about the concepts and definitions used in the euthanasia debate. This suggests that discussions on this subject are inadequately informed and ineffectual. The ethical focus of the euthanasia debate concerns the moral legitimacy of 'voluntary euthanasia'. This article provides an overview and clarification of some of the key ethical issues at the centre of that debate.

An audit of antiretroviral treatment use in HIV-infected patients in a London clinic: the limitations of observational databases when auditing antiretroviral treatment use.

OBJECTIVE: To audit the use of antiretroviral (ARV) treatment in a large treatment clinic in the UK against the British HIV Association (BHIVA) ARV treatment guidelines. METHODS: All patients under follow-up between 1st January 2000 and 1st January 2001 were included. The most recent CD4 count and HIV RNA level prior to 1st January 2001, and the nadir CD4 count and peak HIV RNA level over follow-up, were used to identify which patients should be receiving HAART according to the guidelines. RESULTS: One thousand two hundred and sixty-four patients were included in the analysis (63.8% homosexual, 29.0% heterosexual risk; 72.9% white; 79.2% male). Almost half of patients had ever had a CD4 count below 200 cells/ micro L and over 80% had previously had a viral load above 4 log10 HIV-1 RNA copies/mL. Under 2000 BHIVA guidelines, treatment would be recommended in 77.4% patients. Overall, 819 patients were receiving ARV therapy. Two hundred and eighty-five patients were not receiving treatment when guidelines suggest they should (including 33 patients who were receiving regimens not recommended in the guidelines). These patients were younger, less likely to be homosexual and had higher CD4 nadirs than those who were receiving ARV treatment. Almost half of these patients had previously received ARV therapy but were not currently receiving it. CONCLUSION: Only a small proportion of patients at our centre were not receiving ARV treatment in line with national guidelines. While genuine reasons may exist for these departures from optimal care, this may simply reflect the limitations of using observational databases when auditing treatment use in a clinic setting.

Reasons for modification and discontinuation of antiretrovirals: results from a single treatment centre.

OBJECTIVE: To describe the reasons for, and factors associated with, modification and discontinuation of highly active antiretroviral therapy (HAART) regimens at a single clinic. SUBJECTS: A total of 556 patients who started HAART at the Royal Free Hospital were included in analyses. Modification was defined as stopping or switching any antiretrovirals in the regimen, whereas discontinuation was defined as the simultaneous stopping of all antiretrovirals included in the initial regimen. Reasons were classified as immunological/virological failure (IVF) and toxicities and patient choice/poor compliance (TPC). RESULTS: The median CD4 count at starting HAART was 171 x 10(6) cells/l and viral load 5.07 log copies/ml. During a median follow-up of 14.2 months, 247 patients (44.4%) modified their HAART regimen, 72 due to IVF (29.1%) and 159 due to TPC (64.4%) and a total of 148 patients (26.6%) discontinued HAART. Older patients were less likely to modify HAART [relative hazard (RH), 0.73 per 10 years; P = 0.0008], as were previously treatment-naive patients (RH, 0.65; P = 0.0050), those in a clinical trial (RH, 0.64; P = 0.027) and those who started nelfinavir (RH, 0.57; P = 0.035). Patients who started with four or more drugs (RH, 2.21, P < 0.0001), who included ritonavir in the initial regimen (RH, 1.41; P = 0.035) or who had higher viral loads during follow-up (RH per log increase, 1.51; P < 0.0001) were more likely to modify HAART. CONCLUSIONS: There was a high rate of modification and discontinuation of HAART regimens in the first 12 months, particularly due to toxicities, patient choice or poor compliance.

The developing role of the forensic community nurse.

Mental health professionals are increasingly concerned with the consequences of clinical judgement errors. Such concern has led to an increase in requests for specialist advice from forensic mental health care teams. Consequently, the demand for forensic community mental health nurses (FCMHNs) to provide specialist advice and reports has increased. Such advice can be significant in planning and delivering care.

Evidence of toxic metabolite stress in black South Africans with chronic pancreatitis.

We report the results of a further study to test our hypothesis that toxic metabolite stress is germane to heightened free radical activity and hence to the genesis of chronic pancreatitis. Consecutive black South African patients with clinically quiescent chronic pancreatitis were studied, provided that the diagnosis had been made within the previous 2 years and that they did not have overt liver disease. All of them had been advised to stop drinking alcohol. Analysis of an early morning sample of urine showed a lower ratio of inorganic to ester sulphate (P < 0.001) and a higher ratio of D-glucaric acid to creatinine (P < 0.02) in the group of 14 patients than in 15 local controls, while plasma analysis showed a lower concentration of glutathione (GSH) in the patients (P < 0.001). This evidence of increased utilisation of phase II conjugative pathways of xenobiotic disposal was in keeping with on-going toxic metabolite stress from heightened phase I oxidative metabolism in the group of patients. Parallel studies of theophylline pharmacokinetics showed heightened drug clearance compatible with induced cytochrome P-4501A2 in two patients, whereas increased activity of gamma-glutamyl transferase in serum suggested persisting induction of P-4502E1, as by ethanol, in several others. The contemporaneous increases in free radical activity and utilisation of xenobiotic disposal pathways in Sowetan Africans with chronic pancreatitis is in line with the toxic metabolite concept of disease pathogenesis.

Evidence for early oxidative stress in acute pancreatitis. Clues for correction.

Pancreatic oxidative stress with depletion of pancreatic glutathione is an early feature in all tested models of acute pancreatitis, and sooner or later the problem extends to the lung, irrespective of disease severity, whether toward spontaneous recovery or death from multisystem organ failure. We, therefore, sought evidence of oxidative stress in the human disease by analyzing admission blood samples. We found it from high concentrations of oxidatively altered linoleic acid in serum and vitamin C in plasma (p < 0.001 vs controls or a group of other acute abdominal crises where the proportion of patients with admission Apache II scores < or > 8 was similar). These changes were accompanied by subnormal levels of ascorbic acid in plasma (p < 0.001); selenium (p < 0.001), beta-carotene (p < 0.001), and alpha-tocopherol in serum (p = 0.005 for its molar ratio to cholesterol). Paradoxically, the plasma concentration of S-adenosylmethionine was elevated (p = 0.02), suggesting that this proximate bioactive metabolite of the essential amino acid had backtracked because its intracellular metabolism down the methionine trans-sulfuration pathway toward glutathione synthesis was disrupted. The aberrations transcended putative etiological factor, duration of symptoms, or disease severity. We conclude: (1) that oxidative stress has pervaded the vascular compartment by the time of admission in patients with acute pancreatitis, and, (2) that blood micronutrient antioxidant profiles at this stage are consistent not only with compromised intracellular capacity to synthesize/refurbish glutathione, but also vulnerability of intra- and extracellular lipid targets.

Attitude to treatment and direction of interest of forensic mental health nurses: a comparison with nurses working in other specialties.

The attitudes of nurses working within forensic psychiatry are often perceived as being custodially oriented. Working on this commonly held assumption the authors hypothesized that nurses working within a physically controlled environment such as a Regional Secure Unit would hold more conservative/biological attitudes toward treatment, and would be more 'object'-oriented (as opposed to 'psychologically' oriented) than those working in less physically controlled clinical areas. [For the purpose of this paper the term 'Regional Secure Unit' is used to describe the medium secure facilities that were included in this study, although one of the units did not serve a wholly regional function.] This paper outlines a study that attempted to examine this hypothesis. A total of 84 nurses from three clinical specialties (Regional Secure Units, Acute Admission Wards and Drug Dependence Units) completed the Attitude to Treatment Questionnaire (ATQ) and the Direction of Interest Questionnaire (DIQ) (Caine et al. 1981). Each nurse also completed a demographic information questionnaire, supplying details of age, professional experience and educational attainment. The results indicate no significant differences on measures used between specialty groups. Significant positive correlations were found between age and conservatism on the ATQ, and between ATQ conservatism and DIQ object centredness. Implications of these results are discussed and suggestions for future research are made.

A preliminary report on urinary BT-PABA/PAS excretion index, serum pancreatic isoamylase and faecal chymotrypsin tests of pancreatic dysfunction in Sowetan Africans.

The steady increase in chronic pancreatitis among black Africans at Soweto, RSA, in the past 40 years necessitates an objective and non-invasive test to detect the disease at an early stage. Given the biphasic nature of the disease--secretory hyperfunction with periodic active inflammatory episodes followed by steady exocrine impairment--we assessed three potential aids. Urinary BT-PABA/PAS excretion index (PEI), serum pancreatic isoamylase (PIA) and faecal chymotrypsin activity (FCA) were measured in the following groups: 16 outwardly healthy hospital workers, 16 consecutive patients with calcifying chronic pancreatitis and 19 with abdominal pain ascribed to other conditions (disease controls). (1) Healthy controls had lower PEI than those at Manchester, UK, or Madras, India, from subclinical acinar loss--as shown by lower PABA recovery whereas intestinal absorptive capacity was maintained, as shown by recovery of PAS. (2) Using the popular cut-off for PEI (0.75) only 9 of 14 patients with chronic pancreatitis were identified (sensitivity 64%, 2 tests unsatisfactory), while a value of less than 0.54, the mean -2 S.D. in local controls, yielded sensitivity of 50%. (3) If PEI of less than 0.75 or PIA outside the reference range was taken to indicate the disease, 5 of 9 disease controls would have been classed as chronic pancreatitis (among those with both tests satisfactory): retrospective ultrasound scans did not identify these. (4) Although FCA was less than the preselected cut-off, 5 units/g, in every patient with chronic pancreatitis (100% sensitivity) its poor predictive value was indicated by low specificity: subnormal levels in 4 of 14 and 6 of 16 healthy controls or disease controls, respectively, most of whom had near-normal values of PEI, PIA or both. (5) Collectively, these results suggest a high frequency of subclinical chronic pancreatitis at Soweto, but also that the combination of tests required to identify it may prove impractical--whether in field surveys or hospital practice.

The BT-PABA/PAS test in tropical diabetes.

A 'screening' test is needed to identify patients with chronic pancreatitis among diabetics in tropical field surveys. We have examined the potential diagnostic yield of the BT-PABA/PAS test of exocrine pancreatic function in this setting. The recoveries of both PABA and PAS in eight healthy controls from Madras, south India, were lower than in controls from Manchester, north west England (mean +/- S.D., 51 +/- 11 vs. 79 +/- 7%, P < 0.001 for PABA; 52 +/- 11% vs. 81 +/- 7%, P < 0.001 for PAS) but the % PABA/PAS excretion index (PEI) was similar (0.96 +/- 0.14 vs. 0.96 +/- 0.06). Using a cut-off value of 0.75 for the PEI in a study group including eight patients with chronic pancreatitis and 26 with primary forms of diabetes, test sensitivity was 75%, specificity 92%, positive predictive value 75%, negative predictive value 92% and efficiency 88%.