Cross-sectional observations on the natural history of asthma.

BACKGROUND: Asthma is a major health care problem that affects all ages. It is uncertain whether asthma is a single clinical entity or a grouping of separate clinical syndromes that share a common set of treatment guidelines. AIM: To observe the symptoms, treatment step, and health service utilisation of a population of patients throughout the United Kingdom (UK) listed on an asthma register. DESIGN OF STUDY: A cross-sectional study and clinical assessment of asthma patients. SETTING: A total of 12,203 patients from 393 general practices throughout the UK. METHOD: A database was used to observe the symptoms, treatment step, and health service utilisation of the asthma patients. RESULTS: Children aged up to four years had a distinctive profile of symptoms, including night time cough. They also experienced increased health service utilisation including a high hospital admission rate. Symptoms in adults became more common with increasing age. The pattern of symptoms in patients aged 45 years and over suggest many patients on asthma registers may have chronic obstructive pulmonary disease. Patients aged 16 to 30 years showed a different pattern of health service usage to those aged 5 to 15 years and 31 to 45 years, relying more on unscheduled use of health services rather than a review-based management plan. Patients aged 16 to 30 years used less anti-asthma medication than those aged 5 to 15 years and 31 to 45 years. CONCLUSIONS: Databases may be a useful tool with which to study the natural history of asthma, but there are problems with bias. Several clinical subgroups exist within the broad diagnosis label of asthma. Knowledge of how these subgroups of doctor-diagnosed asthma use health services may help clinicians to create individual care plans for groups of patients.     

Pregnancy outcomes and cardiac complications in women with mechanical, bioprosthetic and homograft valves

Objectives Firstly, to compare pregnancy outcomes and cardiac complications in women with: 1. either mechanical or bioprosthetic valves at the mitral site; 2. mechanical valves treated with warfarin or subcutaneous heparin. Secondly, to determine pregnancy and cardiac outcomes in women with aortic homograft valves.
Design Historical cohort study.
Setting Greenlane Hospital, Auckland, New Zealand.
Population Young women (   n = 255  ) who had valve replacements between 1972 and 1992. Seventy-nine women underwent 147 pregnancies.
Main outcome measures Pregnancy loss, cardiac complications.
Results Pregnancy loss occurred in 59% of pregnancies with mitral mechanical valves (   n = 50  ) and 7% with mitral bioprosthetic valves (   n = 33  ) (RR 8.20,95% CI2.10–31.93). Pregnancy loss rate was 70% in pregnancies treated with warfarin, compared with 25% for those switched from warfarin to heparin (RR 2.81, 95% CI 1.03–7.73). All heparin-associated losses occurred in the first trimester, whereas there were four stillbirths with warfarin. Cardiac complications occurred in 10 pregnancies (20%) in the women with mitral mechanical valves and four (13%) with mitral bioprosthetic valves (RR 1.55, 95% CI 0.53–4.52). All four thromboembolic complications with mechanical valves occurred in the 14 women treated with heparin throughout pregnancy. Structural valve deterioration occurred in four pregnancies (10%) with mitral bioprosthetic valves. No cardiac complications or known pregnancy losses occurred with aortic homograft valves (   n = 41  ).
Conclusion The high pregnancy loss rate in women with mitral mechanical valves was associated with warfarin throughout pregnancy, whereas the thromboembolic cardiac complications were associated with heparin. Pregnancy outcome was very good in women with bioprosthetic and homograft valves.     

Sleeping position and sudden infant death syndrome (SIDS): effect of an intervention programme to avoid prone sleeping

The proportion of prone sleeping among sudden infant death syndrome (SIDS) victims and infants in general, and the rate of SIDS were prospectively studied in the county of Hordaland, Norway, three years before (1987–89) and three years after (1990–92) a campaign to discourage prone sleeping. Before the campaign, 64% of random reference infants were put prone versus 8% after (p < 0.0001). Concurrently, the rate of SIDS decreased from 3.5 to 1.6 per 1000 live births (63 infants before and 30 after the campaign, p = 0.0002). Prone sleeping was not considered a statistically significant risk factor for SIDS before (OR 2.0,95% CI 0.8–4.5), but was highly significant (OR 11.3,95% CI 3.6–36.5) after the campaign. Prone sleeping is an important risk factor for SIDS, but the association may be missed in epidemiological studies if prone is the predominant sleeping position. Behaviour with regard to sleeping position may be changed rapidly by means of a simple campaign.     

Body mass index centile charts to assess fatness of British children.

Body mass index (BMI) relates weight to height and reflects the shape of a child, but because of age dependency it has not been used conventionally for the estimation of fatness in children. From measurements of Tayside children (n = 34,533) centile charts were constructed for BMI (wt/ht2) from the raw data of height and weight, using Cole''s LMS method for normalised growth standards. These data were compared with the only available European BMI charts published from data of French children obtained over a period of 24 years from 1956-79. British children appear to be ''fatter''. Within a subgroup (n = 445) the BMI values were correlated with estimations of body fat, for boys and girls, from skinfold thickness (r = 0.8 and 0.81) and bioelectrical impedance (r = 0.65 and 0.7). The limits of acceptable BMI have yet to be defined.     

Acute rejection in the elderly recipient: Influence of age in the outcome of kidney transplantation

Since the immune response in older recipientsis weaker they should be less likely to rejecta transplanted organ and should need lessaggressive immunosuppressive treatment. Our aimwas to record the incidence and severity ofepisodes of acute rejection (AR), estimate theinfluence of these events on graft survival ofelderly recipients (60) and to comparethese with that in younger ones.We performed 363 kidney transplants between1/94 and 12/98, and recorded clinical andimmunological data, incidence-severity of ARand cause of graft loss. Patients were dividedinto two groups, according to the age attransplantation: A (<60, n = 281/77.4%) and B( 60, n = 82/22.6%). The percentage ofaging recipients and mean age of donors andrecipients increased throughout the period.Although the incidence of ATN was higher in theolder group (29% vs.19%, p < 0.0001) thenumber of graft biopsies was equal in bothgroups. The incidence of AR was similar, 33.4%vs. 26.8%, pNS. The number of AR episodes perpatient was 0.44 and 0.41 respectively. Theseverity of AR was: Banff grade I: A (40.3%)/B (45.7%) pNS; grade II: A (44.1%)/B(48.57) pNS; grade III: A (15.5%)/B (5.7%)pNS. Younger recipients presented a higherlevel of panel-reactive antibodies (PRA) (4.3%vs. 2.07%, p = 0.01). One-year patient survivalwas 96%/91% (p<0.05) and graft survivalwas 81%/78% (pNS) respectively.The age of recipient does not seem to haveinfluenced the incidence-severity of AR or thegraft survival. Thus immunosuppression shouldbe individualised for each patient and shouldnot depend on the age at transplantation.     

Identification of the key amino acids of gliai cell line-derived neurotrophic factor family receptor alpha 1 involved in its biological function

Glial cell line-derived neurotrophic factor （GDNF） plays a critical role in neurodevelopment and survival of midbrain dopaminergic and spinal motor neurons in vitro and in vivo. The biological actions of GDNF are mediated by a two-receptor complex consisting of a glycosylphosphatidylinositol-linked cell surface molecule, the GDNF family receptor alpha 1 （GFR alpha 1）, and receptor protein tyrosine kinase Ret. Although structural analysis of GDNF has been extensively examined, less is known about the structural basis of GFR alpha 1 function. In this study, based on evolutionary trace method and relative solvent accessibility prediction of residues, a set of trace residues that are solvent-accessible was selected for site-directed mutagenesis. A series of GFR alpha 1 mutations was made, and PC12 cell lines stably expressing different GFR alpha 1 mutants were generated. According to the survival and differentiation responses of these stable PC12 cells upon GDNF stimulation and the GDNF- GFR alpha 1-Ret interaction assay, residues 152NN153, Arg259, and 316SNS318 in the GFR alpha 1 central region were found to be critical for GFR alpha 1 binding to GDNF and eliciting downstream signal transduction. The single mutation R259A in the GFR alpha 1 molecule simultaneously lost its binding ability to GDNF and Ret. However N152A/N153A or S316A/N317A/ S318A mutation in the GFR alpha 1 molecule still retained the ability to bind with Ret. These findings suggest that distinct structural elements in GFR alpha 1 may be involved in binding to GDNF and Ret.     

Cardiac Perforation and Tamponade During Transjugular Intrahepatic Portosystemic Shunt Placement

A patient developed acute severe hemodynamic compromise during a transjugular intrahepatic portosystemic shunt (TIPS) procedure for intractable ascites. Rapid clinical and radiographic evaluation of the patient disclosed pericardial blood and cardiac tamponade as the cause, probably due to right heart perforation from guidewire and catheter manipulation. The tamponade was successfully treated percutaneously, and the patient survived. Cardiac tamponade should be considered in the differential diagnosis of patients who develop hypotension during TIPS placement.     

Practice MRI: Reducing the need for sedation and general anaesthesia in children undergoing MRI

The aim of this study was to evaluate the effectiveness of a practice magnetic resonance unit, in preparing children to undergo magnetic resonance procedures without general anaesthesia (GA) or sedation. The records of children who attended the practice MRI between February 2002 and April 2004 were retrospectively reviewed. Each record was assessed as to whether the child had passed or failed the practice MRI intervention. Those children who were considered to have passed and were proceeded to a clinical non‐GA MRI had the report of the clinical scan reviewed. If the scan had been reported as non‐diagnostic because of movement artefact it was classified as a failed scan, otherwise it was considered a pass. One hundred and thirty‐four children undertook a practice MRI (age range 4.1–16.1 years, median age 7.7 years, 47% boys) and 120/134 (90%) passed the practice session. In all, 117/120 (98%) subsequently had a clinical non‐GA MRI and 110/117 (94%) passed (median age 7.8 years, 47% boys). Preparation is a safe and effective method to reduce the need for sedation and GA in children undergoing a clinical MRI scan. It provides a positive medical experience for children, parents and staff, and results in cost savings for the hospital.