Appetite hormones and the transition to hyperphagia in children with Prader-Willi syndrome.

OBJECTIVE: Prader-Willi syndrome (PWS) is a genetic neurodevelopmental disorder with several nutritional phases during childhood proceeding from poor feeding, through normal eating without and with obesity, to hyperphagia and life-threatening obesity, with variable ages of onset. We investigated whether differences in appetite hormones may explain the development of abnormal eating behaviour in young children with PWS. SUBJECTS: In this cross-sectional study, children with PWS (n=42) and controls (n=9) aged 7 months-5 years were recruited. Mothers were interviewed regarding eating behaviour, and body mass index (BMI) was calculated. Fasting plasma samples were assayed for insulin, leptin, glucose, peptide YY (PYY), ghrelin and pancreatic polypeptide (PP). RESULTS: There was no significant relationship between eating behaviour in PWS subjects and the levels of any hormones or insulin resistance, independent of age. Fasting plasma leptin levels were significantly higher (mean ± s.d.: 22.6 ± 12.5 vs 1.97 ± 0.79 ng ml(-1), P=0.005), and PP levels were significantly lower (22.6 ± 12.5 vs 69.8 ± 43.8 pmol l(-1), P<0.001) in the PWS group compared with the controls, and this was independent of age, BMI, insulin resistance or IGF-1 levels. However, there was no significant difference in plasma insulin, insulin resistance or ghrelin levels between groups, though PYY declined more rapidly with age but not BMI in PWS subjects. CONCLUSION: Even under the age of 5 years, PWS is associated with low levels of anorexigenic PP, as in older children and adults. Hyperghrelinaemia or hypoinsulinaemia was not seen in these young children with PWS. Change in these appetite hormones was not associated with the timing of the transition to the characteristic hyperphagic phase. However, abnormal and/or delayed development or sensitivity of the effector pathways of these appetitive hormones (for example, parasympathetic and central nervous system) may interact with low PP levels, and later hyperghrelinaemia or hypoinsulinaemia, to contribute to hyperphagia in PWS.

Pre-, peri- and postnatal complications in Prader-Willi syndrome in a UK sample.

BACKGROUND: Few studies describe in detail the pregnancy and early development of infants with Prader-Willi syndrome (PWS). However, variations at these early stages may partially account for differences in the later phenotype. A recent paper described an abnormally high number of problems in pregnancy and early infancy in a large sample of people with PWS but this sample was not homogeneous with respect to age and potentially liable to cohort effects. AIMS: To describe the early development of infants with PWS, younger and more homogeneous for age, and to investigate whether such high rates of perinatal problems are still present despite medical advances and whether there are differences according to the genetic subtypes. STUDY DESIGN: Using a structured interview, data were collected from mothers and from relevant GP and hospital records. SUBJECTS: Forty-six babies with PWS, born in a six-year period 2000-2006, and their mothers. OUTCOME MEASURES: Problems arising during pregnancy, the birth process and the neonatal period and the birth characteristics of the babies. RESULTS: An abnormally high number of problems associated with the early developmental period similar to those previously reported were observed. The only significant difference between the genetic subtypes was that mother's age was positively correlated with birth weight for UPD (and negatively correlated for deletion subtypes). CONCLUSIONS: High rates of, and variability in, the nature and severity of problems arising during early development have been confirmed. To establish whether variability in the later phenotype is influenced by such differences requires a longitudinal study.

Improving decision-making and documentation relating to do not attempt resuscitation orders.

INTRODUCTION: Do not attempt resuscitation (DNAR) decision-making and recording in case notes can be poor. We have audited current practices pertaining to DNAR orders in a district hospital before and after the introduction of a standardised order form (SOF). METHODOLOGY: DNAR decisions in medical case notes were audited before and after the introduction of a SOF. All aspects of the decision were scrutinised against recommended guidelines (BMA/RCN/RC (UK) London: BMA, 1999). RESULTS: Case notes of 156 patients were examined. A total of 62 (39.7%) had combined case note and SOF documentation (Gp1), while 94 (60.3%) had case note documentation only (Gp2). Some 61/62 (98.4%) of DNAR indications in Gp1 were in accordance with guidelines versus 81/94 (86.2%) in GP2 (P<0.01) and 50/62 (80.6%) of decisions were reviewed in GP1 versus 36/94 (38.3%) in GP2 (P<0.001). More decisions were authorised by consultants in GP1 (56/62 (90.3%) vs. 35/94 (37.2%) P<0.001) and had active patient participation (9/62 (14.5%) vs. 1/94 (1.1%) P<0.001) compared with Gp2. CONCLUSION: Documentation of DNAR decisions in medical case notes is poor. Standardised order forms, based on recommended national guidelines that complement case note entries, improve the process and recording of this sensitive decision.

Nocturnal leg cramps in older people.

Nocturnal leg cramps are common in older people. Such cramps are associated with many common diseases and medications. Physiological methods may be useful for preventing cramps in some people, but there have been no controlled trials of these approaches. Quinine is moderately effective in preventing nocturnal leg cramps. However, there are concerns about the risk/benefit ratio with this drug. In patients with severe symptoms, a trial of 4-6 weeks' treatment with quinine is probably still justified, but the efficacy of treatment should be monitored, for example using a sleep and cramp diary.

Prevalence of, and risk factors for, physical ill-health in people with Prader-Willi syndrome: a population-based study.

The medical findings from a population-based study of Prader-Willi syndrome (PWS) are discussed (in which birth incidence of PWS was estimated at 1:22,000 and death rate at over 3% per annum). In this study the prevalence of specific medical disorders that might account for a shortened life expectancy were investigated. Of all people with a possible diagnosis of PWS, only those meeting clinical criteria and/or with a confirmed genetic diagnosis were included in the study. Sixty-six individuals, 40 males and 26 females with a mean age of 19 years (range of 0 to 46 years) agreed to participate in the population-based study group. A prevalence rate of 25% for non-insulin dependent diabetes mellitus (NIDDM) was found in adults. Mean age at onset was 20 years. Those with NIDDM had a higher past maximum body weight and a greater likelihood of positive family history. Nearly 50% across the age groups reported a history of recurrent respiratory infections. High rates of fractures (29%), leg ulceration (22% in adults), sleep disorders (20%), and severe scoliosis (15% in childhood) were also reported. It is postulated that hypotonia is a possible contributory factor to the risk of strabismus, scoliosis, and respiratory infections. Other causes of morbidity, in particular the high rates of NIDDM, may be due to a failure to manage over-eating resulting in severe obesity. Early diagnosis and clear guidance to families about these risks and how they might be prevented is recommended. It is hypothesized that the high pain threshold may result in the presence of some illness not being apparent.

Adverse cutaneous reaction to naproxen: a missed diagnosis fortuitously resolved.

A 91-year-old man presented with a one-month history of swollen legs and dyspnoea. He also complained of a 16-year chronic rash that had caused him considerable morbidity and cosmetic problems. He had been taking naproxen for several years for osteoarthritis. Clinical examination demonstrated bilateral pitting oedema of the leg and a widespread excoriated rash that affected most of his body. A clinical diagnosis of fluid retention secondary to naproxen was made. Stopping naproxen led not only to the resolution of his leg oedema and dyspnoea, but also to the prompt and complete remission of the rash. Reviewing the patient's history revealed that the rash had almost certainly first appeared when naproxen was started many years previously.

Spironolactone therapy in older patients--the impact of renal dysfunction.

Low dose spironolactone reduces the risk of death from heart failure. We examined the effects of spironolactone on potassium homeostasis in a cohort of elderly patients with congestive heart failure (CHF). Eighteen patients >70 years, mean 80.5 (+/- SD 6.3) with New York Heart Association CHF Grade II-IV were enrolled. All patients were commenced on 25 mg spironolactone daily. The dose was reduced to 12.5 mg daily when hyperkalemia (potassium>5.0) occurred. A serum creatinine of >150 micromol/l was defined as indicating renal impairment (RI). Blood pressure, pulse rate, urea, creatinine, Na+ and K+ were measured at baseline, day 2-5, day 28 and more often if clinically indicated. Nine of those recruited had RI. Baseline serum potassium was significantly higher in those with RI, mean 4.56 (+/- 0.30) vs. 4.04 (+/- 0.30) mmol/l (P<0.01). Six patients with RI developed hyperkalemia versus one of those with serum creatinine <150 micromol/l (P<0.05). Serum K+ returned to normal in all patients when the dose of spironolactone was reduced to 12.5 mg daily with one exception in whom the medication was withdrawn. When spironolactone is prescribed to older patients with CHF, hyperkalemia appears more likely in those with RI. Halving the dose to 12.5 mg daily results in normalisation of serum potassium. Older patients commencing spironolactone therapy should have serum potassium monitored frequently, particularly in the presence of RI.

Food intake patterns of marathon runners.

A group of marathon runners (290 males, 54 females, mean age 39.7 +/- 0.7 years) who participated in the Los Angeles Marathon recorded their food and fluid intake throughout a 3-day period, with the time of day denoted for each entry. Investigators coded each subject's food intake according to six time periods: 5:00-8:59 a.m., 9:00-10:59 a.m., 11:00 a.m.-1:59 p.m., 2:00-3:59 p.m., 4:00-7:59 p.m., and 8:00 p.m.-4:59 a.m. The average intake of the runners consisted of 314 +/- 6 g (52.3%) carbohydrates, 83.2 +/- 2.0 g (30.7%) fat, and 99.7 +/- 2.3 g (16.5%) protein. Time periods for breakfast (13.7%), lunch (23.8%), and supper (34.0%) accounted for 71.5% of total caloric intake, with snack time periods contributing 28.5%. Breakfast calories were 68.9 +/- 0.9% carbohydrate and 20.4 +/- 0.7% fat in contrast to supper calories, which were 47.7 +/- 0.8% and 31.8 +/- 0.6%, respectively. A sizable proportion of the daily caloric intake of recreational marathon runners is contributed by snacks and food intake after 4:00 p.m.

Supplementation patterns in marathon runners.

The purpose of the present investigation was to study the use of supplements in a large group of endurance runners (no. = 347) who had participated in the 1987 Los Angeles Marathon. Three-day dietary records were analyzed for nutrient content and supplement usage. The runners' supplementation patterns with respect to demographics, dietary quality, training habits, and race performance were investigated. In general, no significant associations were found between supplement use and the aforementioned variables. Use of supplements, especially vitamins C and E, calcium, and zinc, increased with age (p less than .05). Daily use of at least one type of supplement was reported by 29% of the runners; 48% reported use of at least one type of supplement within the 3-day period.

Nutrient intake of marathon runners.

Three-day food records from a large group of marathon runners (291 men, 56 women) were analyzed and compared to various standards of dietary quality. Intake by the runners exceeded two-thirds of the Recommended Dietary Allowance for all nutrients except vitamin D and zinc in female runners. Energy and nutrient intake levels in the marathon runners were higher than those of the general U.S. population except for total fat, vitamin B-12, and zinc in both men and women and sodium in men. In general, runners consumed better diets than the general population. However, both caloric intake and percent energy as carbohydrate were lower than recommended for individuals engaging in endurance exercise. The need for professional help in planning high-carbohydrate diets for runners is indicated. Increasing amounts of training were not associated with significant increases in nutrient densities across three activity categories within this group of runners. However, more than 75% of the runners perceived their diets to be much improved after they began regular training (men 8.2 +/- 0.3 years of running experience, women 6.7 +/- 0.6). Together, these data suggest that regular moderate-to-heavy endurance exercise is associated with a better quantity and quality of nutrient intake than that found in the general population, which may in part be related to the adoption of such exercise by previously sedentary individuals.

The elastase activity of alveolar macrophages: measurements using synthetic substrates and elastin.

Hamster, rat, guinea pig, and rabbit alveolar macrophage extracts were tested for elastase activity using elastin suspended in agar and two synthetic substrates, p-nitrophenyl N-tert-butyloxycarbonyl L-alaninate (NBA) and succinyl-L-alanyl-L-alanyl-L-alanine-p-nitroanilide (SLAPN). Activity against NBA was easily detectable, but there was no activity against SLAPN or against elastin-agar, although the assay procedures employing these substrates measured as little as 50 and 2 ng of pancreatic elastase, respectively. We concluded that unstimulated alveolar macrophages from these animals do not contain elastase, and that NBA activity is misleading as an indicator of elastolytic activity in crude alveolar macrophage extracts from these species.