Analysis of faecal neutral sterols in patients with familial adenomatous polyposis by gas chromatography-mass spectrometry

Previous studies have suggested that patients with familial adenomatous polyposis (FAP) have increased faecal excretion of cholesterol but a reduction in cholesterol metabolites. It was consequently proposed that the degree of faecal cholesterol degradation could be used as a means of diagnosis. Developments in the extraction and analysis of faecal neutral sterols as well as the accurate means of diagnosing FAP by DNA analysis and indirect ophthalmoscopy has necessitated a re-examination of this proposal. Faecal neutral sterols were analysed in 10 patients with untreated FAP following a complete 5-day stool collection and compared with 9 healthy control subjects (including 4 siblings) closely matched for age and sex. The median [25 and 75, percentiles] stool wet weights were similar between the FAP (97.5 [69, 192] g · 24 h^-1) and the control (116 [61.5, 137] g · 24 h^-1) groups. Faecal cholesterol concentration was similar in the two groups (FAP=2.3 [1.4, 4.2]; control=3.5 [1.0, 6.0] mol · g^-1 dry wt) as was the concentration of total neutral sterols not including plant sterols (FAP=17.2 [13.4, 21.0]; control=18.2 [7.4, 21.6] mol · g^-1 dry wt). There were no significant differences in the proportions of cholesterol metabolised between the FAP (82.3 [74.2, 93.5]%) and control (72.1 [5.7, 81.3]%) groups. This study does not support the notion that faecal neutral sterol metabolism is uniquely different in patients with FAP.

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Résumé Des études précedentes avaient suggéré que les malades avec polypose adénomateuse familiale (PAF) avaient une excrétion fécale augmentée de choléstérol mais une réduction des métabolìtes du choléstérol. On a donc proposé que les degrés de dégradation fécale du choléstérol puisse être utilisée comme moyen de diagnostic. Le développement dans l'extraction et l'analyse des stérols neutres fécaux aussi bien que des moyens appropriés de diagnostiquer la PAF par analyse du DNA et ophthalmoscopie indirecte a nécessité un ré-examen de cette proposition. Les stérols neutres fécaux, ont été analysés chez 10 patients avec une PAF non traitée après une collection complète des matières de 5 jours et comparés avec 9 sujets contrôles sains (comprenant 4 enfants de mêmes parents) étroitement appareillés pour l'âge et le sexe. Les poids moyens (25 et 75 percentiles) de selles humides étaient similaires chez les PAF (97.5 (69, 192) g · 24 h^-1) et les contrôles (116 (61.5, 137) g · 24 h^-1). La concentration de choléstérol fecal était similaire dans les deux groupes (PAF=2.3 (1.4, 4.2); controle=3.5 (1.0, 6.0) mol · g poids sec) de même que la concentration de stérols neutres totaux stéroïdes végétaux exclus (PAF=17.2 (13.4, 21.0); controle 18.2 (7.4, 21.6) mol · g poids sec). Il n'y avait pas de différence significative dans les proportions de choléstérol métabolisé entre les PAF (82.3 (74.2, 93.5)%) et les contrôles (72.1 (5.7, 81.3)%). Cette étude ne confirme pas la notion que le métabolisme des stérols neutres fécaux est uniquement différent chez les patients avec une PAF.

     

Headache and family history

In two headache questionnaire surveys we inquired about the occurrence of headache in the mothers, fathers, siblings and children of the respondents. In total, 633 people completed valid questionnaires, 260 in the first survey and 373 in the second. The hypothesis was that familial headache occurrence would be positively associated with headache frequency. In each survey, the regression of headache frequency on the number of parents having headache was highly significant. Neither sex nor the sibling and children variables were significant predictors. In the cross-tabulations of the parental occurrence of headache with headache frequency we saw a clear "break-point" between the "no headache" and the headache frequency categories studied. For the final analyses the dichotomy "headache/no headache" was related in fourfold tables to headache occurrence in the father and the mother separately, and to the number of headache parents. The positive associations were not simply due to the large number of migraine cases since they remained after removing the migraineurs.     

Involvement of deprivation and environmental lead in neural tube defects: a matched case-control study

OBJECTIVE: To analyse the prevalence of neural tube defects in small geographical areas and seek to explain any spatial variations with reference to environmental lead and deprivation. SETTING: The Fylde of Lancashire in the north west of England. DESIGN: Cases were ascertained as part of a prospective survey of major congenital malformations in babies born in the Fylde to residents there between 1957 and 1981. A matched case-control analysis used infants with cardiovascular system, alimentary tract, and urinary system malformations as controls. Conditional logistic regression was used to assess the effects of more than 10 micrograms/l lead in drinking water and the Townsend deprivation score. RESULTS: The prevalence of neural tube defects in 1957-73 was higher in Blackpool, Fleetwood, and North Fylde, whereas the three control groups showed no significant spatial variation. In 1957-81 mothers living in electoral wards with either a higher proportion of houses with more than 10 micrograms/l lead in the water or a higher deprivation score had a greater risk of having a baby with a neural tube defect. For spina bifida and cranium bifidum alone, this was also true. For anencephaly, deprivation was less important although the effect of lead was still seen. In some neural tube defects, lead may act independently of other possible factors associated with deprivation. It seemed unlikely that lead levels changed significantly during the survey. The percentage of houses with 10 micrograms/l or more of lead in the water in 1984-5 was similar to that found in Great Britain 10 years previously. CONCLUSION: There is evidence to suggest that lead is one cause of neural tube defects, especially anencephaly. This could link the known preventive actions of hard water and folic acid. Calcium is a toxicological antagonist of lead. One cause of a deficiency of folic acid is impaired absorption secondary to zinc deficiency, which may be produced or exacerbated by lead.     

Auditing paediatric diabetes care and the impact of a specialist nurse trained in paediatric diabetes

AIMS: To define outcome measures for auditing the clinical care of children and adolescents with insulin dependent diabetes mellitus (IDDM) and to assess the benefit of appointing a dedicated paediatric trained diabetes specialist nurse (PDSN). METHODS: Retrospective analysis of medical notes and hospital records. Glycaemic control, growth, weight gain, microvascular complications, school absence, and the proportion of children undergoing an annual clinical review and diabetes education session were assessed. The effect of the appointment of a PDSN on the frequency of hospital admission, length of inpatient stay, and outpatient attendance was evaluated. RESULTS: Children with IDDM were of normal height and grew well for three years after diagnosis, but grew suboptimally thereafter. Weight gain was above average every year after diagnosis. Glycaemic control was poor at all ages with only 16% of children having an acceptable glycated haemoglobin. Eighty five per cent of patients underwent a formal annual clinical review, of whom 16% had background retinopathy and 20% microalbuminuria in one or more samples. After appointing the PDSN the median length of hospital stay for newly diagnosed patients decreased from five days to one day, with 10 of 24 children not admitted. None of the latter was admitted during the next year. There was no evidence of the PDSN affecting the frequency of readmission or length of stay of children with established IDDM. Non-attendance at the outpatient clinic was reduced from a median of 19 to 10%. CONCLUSIONS: Outcome measures for evaluating the care of children with IDDM can be defined and evaluated. Specialist nursing support markedly reduces the length of hospital stay of newly diagnosed patients without sacrificing the quality of care.     

Pain and pain management in newborn infants: a survey of physicians and nurses

BACKGROUND: Despite an increased awareness among clinicians regarding pain and pain management for infants undergoing surgery, pain associated with procedures performed outside the operating room may not be adequately managed. PURPOSE: To examine the beliefs and self-described behavior of physicians and nurses regarding the management of procedural pain in newborn infants. METHODS: A survey was distributed to 467 clinicians (nurses and physicians) working in 11 level II and 4 level III nurseries in a large metropolitan area. Respondents were asked to rate the painfulness of 12 common bedside nursery procedures and how often pharmacologic and nonpharmacologic (comfort) measures are currently used and should be used for those procedures. Demographic data were also collected. RESULTS: Surveys were completed by 374 clinicians (80% response rate). Physicians and nurses believe infants feel as much pain as adults and that 9 of the 12 listed procedures are moderately to very painful. Neither pharmacologic nor comfort measures are believed to be used frequently, even for the most painful procedures. Physicians and nurses believe both pharmacologic and comfort measures should be used more frequently, but nurses believe comfort measures should be used more frequently than do physicians. Beliefs about infant pain and procedural pain were related to pain management preferences. Physicians' but not nurses' ratings were associated with significant personal pain. CONCLUSIONS: Despite their beliefs that infants experience significant procedure-related pain, clinicians believe pain management for infants remains below optimal levels. Barriers to more consistent and effective pain management need to be identified and surmounted.     

Tuberous sclerosis complex and Wolff-Parkinson-White syndrome

This report highlights the association between tuberous sclerosis and Wolff-Parkinson-White syndrome. Ten patients with concurrent diagnoses of Wolff-Parkinson-White syndrome and tuberous sclerosis were identified. Wolff-Parkinson-White syndrome presented early in life, nine cases being diagnosed in the first year. Eight of the 10 cases were male. In eight cases, the syndrome was associated with supraventricular tachycardias, and in nine with cardiac rhabdomyomata. One child died from cardiac failure secondary to obstruction of the left ventricular outflow tract by a rhabdomyoma. Five of nine survivors showed resolution of Wolff-Parkinson-White syndrome on follow up. The accessory pathway was localised in nine patients from surface electrocardiograms: six children had left sided pathways and three had right sided pathways.     

Iron-induced oxidative DNA damage and its repair in primary rat hepatocyte culture

Iron-overload diseases frequently develop hepatocellular carcinoma. The genotoxic mechanism whereby iron is involved in hepatocarcinogenesis might involve an oxidative process via the intermediate production of reactive oxygen species. This was presently investigated by examining kinetics of formation and repair of DNA base lesions in primary rat hepatocyte cultures supplemented with the iron chelate, ferric nitrilotriacetate Fe-NTA (10 and 100 microM). Seven DNA base oxidation products have been identified in DNA extracts by gas chromatography- mass spectrometry, which showed a predominance of oxidized-purines (8- oxo-guanine, xanthine, fapy-adenine, 2-oxo-adenine) above oxidized pyrimidines (5-OHMe-uracil, 5-OH-uracil, 5-OH-cytosine) in control cultures. All these DNA oxidation products revealed a significant dose- dependent increase at 4 to 48 h after Fe-NTA supplementation, among which fapy-adenine showed the highest increase and 5-OH-cytosine was the least prominent. Involvement of iron in this oxidative process was established by a correlation between extent in DNA oxidation and intracellular level of toxic low molecular weight iron. DNA excision- repair activity was estimated by release of DNA oxidation products in culture medium. All the seven DNA oxidation products were detected in the medium of control cultures and showed basal repair activity. This DNA repair activity was increased in a time- and dose-dependent fashion with Fe-NTA. Oxidized-pyrimidines, among which was 5-OHMe-Uracil, were preferentially repaired, which explains the low levels detected in oxidized DNA. Since oxidized bases substantially differed from one another in terms of excision rates from cellular DNA, specific excision- repair enzymes might be involved. Our findings, however, demonstrate that even though DNA repair pathways were activated in iron-loaded hepatocyte cultures, these processes were not stimulated enough to prevent an accumulation of highly mutagenic DNA oxidative products in genomic DNA. The resulting genotoxic effect of Fe-NTA might be relevant in understanding the hepatocarcinogenic evolution of iron-overload diseases.      

Panniculitis in childhood and adolescence

Background: The purpose of the present paper was to describe the clinical manifestations and treatment of patients with panniculitis. Methods: From January 1983 to December 2002, 4294 patients were treated for pediatric rheumatological diseases at Pediatric Rheumatology Unit, University of São Paulo, Brazil. Of these, 35 children and adolescents (0.8%) presented with panniculitis: erythema nodosum (EN) or Weber–Christian disease (WCD). Clinical characteristics, laboratory exams, biopsy of the lesion, treatment and clinical course were studied. Results: Of the 35 patients, 29 presented with EN and six with WCD, one of these with cytophagic histiocytic panniculitis. Mean age at symptom onset was 85 months (6–204 months) and the mean duration of follow up was 55 months (1–144 months). All the patients presented with inflammatory subcutaneous nodules. The patients with WCD presented with systemic manifestations and cutaneous atrophy. The principal etiologies of EN were streptococcal infection (42%), undetermined (13.5%), pulmonary tuberculosis (10%), and acute rheumatic fever (10%). Biopsy of the nodules indicated septal panniculitis in 14 patients with EN and lobular panniculitis without vasculitis in the patients with WCD, one of which had cytophagic histiocytic panniculitis. There was recurrence in 11 patients (38%) with EN and in all those with WCD. Non‐steroidal anti‐inflammatory drugs were used in 15 patients with EN and corticosteroids and/or immunosuppressive drugs in the six patients with WCD. Three patients died. Conclusions: EN is the most frequent panniculitis, with a benign course and is mainly associated with infections. WCD is a severe disease, with systemic involvement, that proceeds with cutaneous atrophy and requires the use of corticosteroids and or immunosuppressive drugs.