Development of diagnostic algorithm for Cushing's syndrome: a tertiary centre experience.

PURPOSE: No consensus exists as the gold standard for Cushing's Syndrome (CS) screening. This study aimed to evaluate the diagnostic accuracy and utility of late-night salivary cortisol (LNSC) and cortisone (LNSE), overnight dexamethasone suppression test (ODST), and urinary free cortisol (UFC) in developing a screening algorithm for CS. METHODS: A retrospective, single-centre analysis on 93 adult patients referred to the Oxford Centre for Diabetes, Endocrinology, and Metabolism for CS evaluation (2017-2022). Data were analysed using binomial logistic regression and area under the receiver-operating curve (AUROC). RESULTS: Fifty-three patients were diagnosed with CS. LNSC (sensitivity 87.5%, specificity 64.9%, AUC 0.76), LNSE (sensitivity 72.4%, specificity 85.7%, AUC 0.79), and ODST (sensitivity 94.7%, specificity 52.1%; AUC 0.74) demonstrated comparable effectiveness for CS diagnosis. Their combined application increased diagnostic accuracy (AUC 0.91). UFC was not statistically significant. Pre-test clinical symptom inclusion improved screening test performance (AUC LNSC: 0.83; LNSE: 0.84; ODST: 0.82). For CD diagnosis, LNSE + LNSC (AUC 0.95) outperformed ODST. Combining these with ACTH levels < 12.6 pmol/L perfectly distinguished MACS (AUC 1.00). ODST (AUC 0.76) exhibited superior performance (sensitivity 100.0%, specificity 52.2%) in MACS detection. CONCLUSIONS: LNSC, LNSE, and ODST are robust tools for CS screening, with their combined use offering the highest diagnostic precision. LNSE, especially when used with LNSC, is highly effective for CD diagnosis, exceeding ODST accuracy. ODST is preferable for MACS identification. Integrating ACTH levels markedly improves differentiation between CD and MACS. Conversely, UFC shows limited diagnostic utility.

Parenchymal involvement on CT pulmonary angiography in SARS-CoV-2 Alpha variant infection and correlation of COVID-19 CT severity score with clinical disease severity and short-term prognosis in a UK cohort.

AIM: To determine if there is a difference in radiological, biochemical, or clinical severity between patients infected with Alpha-variant SARS-CoV-2 compared with those infected with pre-existing strains, and to determine if the computed tomography (CT) severity score (CTSS) for COVID-19 pneumonitis correlates with clinical severity and can prognosticate outcomes. MATERIALS AND METHODS: Blinded CTSS scoring was applied to 137 hospital patients who had undergone both CT pulmonary angiography (CTPA) and whole-genome sequencing of SARS-CoV-2 within 14 days of CTPA between 1/12/20-5/1/21. RESULTS: There was no evidence of a difference in imaging severity on CTPA, viral load, clinical parameters of severity, or outcomes between Alpha and preceding variants. CTSS on CTPA strongly correlates with clinical and biochemical severity at the time of CTPA, and with patient outcomes. Classifying CTSS into a binary value of "high" and "low", with a cut-off score of 14, patients with a high score have a significantly increased risk of deterioration, as defined by subsequent admission to critical care or death (multivariate hazard ratio [HR] 2.76, p<0.001), and hospital length of stay (17.4 versus 7.9 days, p<0.0001). CONCLUSION: There was no evidence of a difference in radiological severity of Alpha variant infection compared with pre-existing strains. High CTSS applied to CTPA is associated with increased risk of COVID-19 severity and poorer clinical outcomes and may be of use particularly in settings where CT is not performed for diagnosis of COVID-19 but rather is used following clinical deterioration.

Faecal immunochemical testing (FIT): sources of result variation based on three years of routine testing of symptomatic patients in English primary care.

Introduction: We aimed to determine the analytical capabilities of a commonly used faecal immunochemical test (FIT) to detect faecal haemoglobin (Hb) in symptomatic people attending primary care in the context of the English NICE DG30 guidance.Materials and Methods: Data obtained from independent verification studies and clinical testing of the HM-JACKarc FIT method in routine primary care practice were analysed to derive performance characteristics.Results: Detection capabilities for the FIT method were 0.5 µg/g (limit of blank), 1.3 µg/g (limit of detection) and 3.0 µg/g (limit of quantitation). Of 33 non-homogenized specimens, 31 (93.9%) analysed in triplicate were consistently categorized relative to 10 µg/g, compared to all 33 (100%) homogenized specimens. Imprecision was higher (median 27.8%, (range 20.5% to 48.6%)) in non-homogenized specimens than in homogenized specimens (10.2%, (7.0 to 13.5%)). Considerable variation was observed in sequential clinical specimens from individual patients but no positive or negative trend in specimen degradation was observed over time (p = 0.26).Discussion: The FIT immunoassay evaluated is capable of detecting faecal Hb at concentrations well below the DG30 threshold of 10 µg/g and is suitable for application in this context. The greatest practical challenge to FIT performance is reproducible sampling, the pre-analytical step associated with most variability. Further research should focus on reducing sampling variability, particularly as post-COVID-19 guidance recommends greater FIT utilization.

Clinical Reliability of point-of-care tests to support community based acute ambulatory care.

OBJECTIVE: To ensure clinicians can rely on point-of-care testing results, we assessed agreement between point-of-care tests for creatinine, urea, sodium, potassium, calcium, Hb, INR, CRP and subsequent corresponding laboratory tests. PARTICIPANTS: Community-dwelling adults referred to a community-based acute ambulatory care unit. INTERVENTIONS: The Abbott i-STATTM (Hb, clinical chemistry, INR) and the AfinionTM Analyser (CRP) and corresponding laboratory analyses. OUTCOMES: Agreement (Bland-Altman) and bias (Passing-Bablok regression). RESULTS: Among 462 adults we found an absolute mean difference between point-of-care and central laboratory analyses of 6.4g/L (95%LOA -7.9 to +20.6) for haemoglobin, -0.5mmol/L (95%LOA -4.5 to +3.5) for sodium, 0.2mmol/L (95%LOA -0.6 to +0.9) for potassium, 0.0mmol/L (95%LOA -0.3 to +0.3) for calcium, 9.0 µmol/L (95%LOA -18.5 to +36.4) for creatinine, 0.0mmol/L (95%LOA -2.7 to +2.6) for urea, -0.2 (95%LOA -2.4 to +2.0) for INR, -5.0 mg/L (95%LOA -24.4 to +14.4) for CRP. CONCLUSIONS: There was acceptable agreement and bias for these analytes, except for haemoglobin and creatinine.

Reduced kidney function at presentation in unselected acute emergency medical admissions: incidence, outcome and associated factors.

We sought to assess the impact of renal impairment on acute medical admissions and to identify potential contributory factors to admissions involving renal impairment at presentation. In a prospective cohort study, 29.5% of all acute medical emergency admissions had an eGFR <60ml/min/1.73m2 at presentation. Of these, 19.9% had definite chronic kidney disease and 8.4% had definite acute kidney injury. Detailed analysis of a random subset of patients with an eGFR <60ml/min/1.73m2 at presentation demonstrated that the major reasons for admission included falls, dehydration and fluid overload. 46% were on diuretics and 53% were on an ACEI or ARB or both. Gastrointestinal disturbance and recent medication changes were common and diuretic use persisted even with diarrhoea or vomiting.

Risk factors for mediastinitis following cardiac surgery: the importance of managing obesity.

BACKGROUND: Mediastinitis is a devastating complication of cardiac surgery. Previous studies have often observed small populations, been retrospective in design, and used a variety of definitions for mediastinitis. AIM: To identify risk factors for mediastinitis, and strategies to minimize its incidence. METHODS: A prospective cohort study of 4883 adult patients who underwent cardiac surgery between October 2003 and February 2009, comparing pre- and peri-operative risk factors, microbial aetiology, requirement for re-admission, length of stay and mortality between patients with and without mediastinitis. FINDINGS: Ninety (1.8%) patients were diagnosed with mediastinitis. Microbial aetiology was defined for 75 patients. Staphlyocococcus aureus was the most common isolate (30 episodes; 15 due to meticillin-resistant S. aureus). Univariate analysis revealed the following pre-operative factors associated with mediastinitis: age; body mass index; diabetes; modified logistic European System for Cardiac Operative Risk Evaluation score; urgent admission; and longer pre-operative stay (P < 0.05). Associated peri-operative factors were: combined coronary artery bypass grafting plus aortic valve replacement; longer aortic cross-clamp time; and longer cardiopulmonary bypass time (P < 0.005). Multi-variate analysis revealed that higher body mass index, combined coronary artery bypass grafting plus aortic valve replacement, and older age were associated with mediastinitis (P < 0.05). Mediastinitis was associated with re-admission to hospital, longer inpatient stay and reduced long-term survival (P < 0.05). CONCLUSION: Mediastinitis is associated with worse short-term outcomes (re-admission, length of stay) and reduced long-term survival. Obesity is the only modifiable pre-operative risk factor for mediastinitis. It may be possible to reduce risk through pre-operative weight loss programmes before elective surgery.

Hypophosphataemia with non-tenofovir-containing antiretroviral therapy.

Hypophosphataemia with tenofovir (TDF) treatment has been well described. The role of HIV infection and of other antiretroviral (ART) agents in hypophosphataemia has received less attention. The aim of this study was to determine the prevalence of hypophosphataemia in HIV-positive adults. We measured the fasting plasma phosphate level and estimated glomerular filtration rate (eGFR) in 123 HIV-positive patients. A total of 26% had hypophosphataemia and 11% had hypophosphataemia of grades 2-4 (0.65 mmol/L or less). Hypophosphataemia of any grade was more frequent in those who were ART-treated than ART-naive (35% versus 10%; P = 0.0001). Multiple linear regression analysis showed no significant association between phosphate level and gender, TDF status, duration of ART, duration of HIV infection and eGFR. Increasing age was significantly associated with a very small rise in phosphate level. Isolated hypophosphataemia was significantly more frequent in HIV-positive subjects receiving ART than ART-naive individuals, irrespective of the drug regimen.

Persistent individual tracking within overall improvement in HbA1c in a UK paediatric diabetes clinic over 15 years.

INTRODUCTION: There is some evidence of long-term tracking of HbA(1c) levels within diabetes centres, but little evidence of individual tracking. METHODS: HbA(1c) levels of children in the clinic over a period of 15 years were retrieved from the clinical chemistry laboratory information system. We measured the correlation of HbA(1c) between years (Spearman and Pearson rank correlation), as well as the relationship of HbA(1c) with age and the change over time in the clinic. RESULTS: Data were collected from 362 children and young people [158 female (44%)], aged 0-18 years (median 10.4 years), with 0-13.6 years of follow-up (median 4.7 years). Mean HbA(1c) levels fell from 9.3 ± 1.5% (78 ± 16 mmol/mol) in 2001 to 8.1 ± 1.3% (65 ± 14 mmol/mol) in 2009 in those at least 6 months after diagnosis (P<0.0001). HbA(1c) levels gradually rise with increasing age. HbA(1c) levels from year to year are significantly correlated. This is better for adjacent than subsequent years, but there is a significant correlation up to 9 years from diagnosis. Only 4 of 49 children with a 6-month HbA(1c) level of 9% (75 mmol/mol) or more had a long-term (2-5 years) median HbA(1c) <8% (64 mmol/mol). CONCLUSIONS: HbA(1c) levels track in individuals within an improvement in overall clinic levels, suggesting that, if optimal control can be achieved in the first 6 months, it can persist for up to 9 years.

An 'n-of-1' placebo-controlled crossover trial of intravenous immunoglobulin as adjuvant therapy in refractory pemphigus vulgaris.

BACKGROUND: Pemphigus vulgaris (PV) is an organ-specific autoimmune blistering mucocutaneous disorder that is potentially fatal. High-dose intravenous immunoglobulin (IVIg) is increasingly used in the treatment of autoimmune diseases and it has been reported that it may also be effective in PV. OBJECTIVES: To evaluate prospectively the efficacy of IVIg for PV using an 'n-of-1' placebo-controlled trial. METHODS: A randomized, placebo-controlled, crossover trial of IVIg was conducted in a single patient with severe PV, comprising two phases of six consecutive months of either IVIg or placebo infusion. Before the commencement of the trial, the patient had received 18 months of IVIg but concerns about the continuing therapeutic efficacy of IVIg led to the double-blind placebo-controlled 'n-of-1' trial of IVIg. RESULTS: Pemphigus autoantibody titres were significantly higher when on placebo compared with IVIg treatment (median 1 : 80 vs. 1 : 20, P = 0.007), desmoglein 3 (126 vs. 79, P = 0.004) and desmoglein 1 antibody levels (126 vs. 94, P = 0.004). There was a significant improvement in subjective disease activity scores while on IVIg compared with placebo (mean overall score 11.6 vs. 20.6, P < 0.0001). CONCLUSIONS: The results of this study confirm a beneficial effect of IVIg in the management of refractory PV.

Longitudinal screening of serum lipids in children and adolescents with Type 1 diabetes in a UK clinic population.

AIMS: To determine the prevalence of abnormal lipid levels in a large group of children and adolescents with Type 1 diabetes and to examine the changes longitudinally. In addition, to study the relationships of any lipid abnormalities to glycaemic control, age and duration of diabetes. METHODS: Non-fasting blood samples were taken annually from all the patients in the Oxford Children's diabetes clinic and total cholesterol (TC), high-density lipoprotein (HDL) cholesterol, triglycerides (TG) and glycated haemoglobin (HbA(1c)) measured over a period of 8 years. Low-density lipoprotein (LDL) cholesterol and non-HDL were calculated from these values and compared. Tests performed less than 4 months after diagnosis were excluded. RESULTS: A total of 229 children had complete data from more than 1 year and 798 sets of data were examined. TC was lower in males and increased with duration of diabetes and with increasing HbA(1c). HDL cholesterol fell with increasing age, but independently increased with duration, and was not related to HbA(1c). LDL cholesterol and non-HDL cholesterol were highly correlated (r = 0.9). Both were lower in males and increased with duration of diabetes. Non-HDL cholesterol increased with HbA(1c). A total of 23.7% had HDL cholesterol < 1.1 mmol/l and 22.5% had TC > 5.2 mmol/l. Thirty-eight per cent had LDL cholesterol > 2.6 mmol/l and 10.8% > 3.4 mmol/l, the thresholds for lifestyle and drug intervention respectively. CONCLUSIONS: Abnormalities in plasma lipid levels are common in this age group and the prevalence increases with poor glycaemic control and with duration of diabetes. Around 10% of adolescents would fit criteria for lipid-lowering medication in adults, but further study is needed to examine the risks and benefits in this age group.

Diabetes mellitus among young adults in Sri Lanka--role of GAD antibodies in classification and treatment: the Sri Lanka Young Diabetes study.

AIMS/HYPOTHESIS: Diabetes mellitus is increasing among young adult South Asians. The aim of this study was to determine the prevalence and phenotypic characteristics of diabetes subtypes based on GAD65 autoantibody (GADA) status in those with young adult-onset diabetes in Sri Lanka. METHODS: Clinical, metabolic and GADA data were available for 992 consecutively recruited individuals with diabetes aged < or =45 years (age at diagnosis 16-40 years). Participants were classified according to the following definitions: type 1 diabetes, insulin-dependent <6 months from diagnosis; latent autoimmune diabetes in adults (LADA), GADA-positive, age > or =30 years and insulin-independent > or =6 months from diagnosis; type 2 diabetes, GADA-negative and insulin-independent > or =6 months from diagnosis. RESULTS: The median (interquartile range) age at diagnosis and diabetes duration were 33.0 (29.0-36.1) and 4.0 (1.1-7.1) years, respectively; 42.1% were male. GADA positivity was seen in 5.4% of participants (n = 54) and GADA levels negatively correlated with age at diagnosis (p < 0.0001), BMI (p < 0.0001) and time to insulin requirement (p = 0.006). Type 1 diabetes, type 2 diabetes and LADA were present in 7.0%, 89.7% and 2.6%, respectively. The remaining 0.7% of the participants were GADA-positive, insulin independent > or =6 months from diagnosis and were diagnosed at age <30 years. The metabolic syndrome and homeostasis model assessment of beta cell function (HOMA %B) were lowest in GADA-positive type 1 diabetes and increased progressively in latent autoimmune diabetes, GADA-negative type 1 diabetes and type 2 diabetes. Among those requiring insulin, 69.2% had fasting C-peptide levels in the lowest quartile, whereas only 19.5% were GADA-positive (p < 0.0001). CONCLUSIONS/INTERPRETATION: The prevalence of GADA-positive autoimmune diabetes is low among individuals with young adult-onset diabetes in Sri Lanka. Young-onset diabetic phenotypes appear as a continuum from autoimmune type 1 diabetes to type 2 diabetes.

Craniopharyngiomas in children and adults: systematic analysis of 121 cases with long-term follow-up.

BACKGROUND: Craniopharyngiomas account for 2-5% of all primary intracranial tumours. Despite their benign histological appearance, they are often associated with an unfavourable prognosis and their optimal treatment remains controversial. AIM: To analyse the natural history and treatment outcome of children and adults presenting to the Departments of Paediatrics and Endocrinology with craniopharyngioma between 1964 and 2003. PATIENTS AND METHODS: The records of 121 patients (age range 2.5-83 years, 42 aged < 16 and 79 aged > or = 16) were identified. The mean follow-up period since presentation was 103 months (8.6 years) (range 0.3-468 months). Sixteen patients underwent gross total removal (A), 3 gross total removal + radiotherapy (B), 51 partial removal (C), 33 partial removal + radiotherapy (D), 6 cyst evacuation alone (E) and 3 cyst evacuation + radiotherapy (F). The clinical, imaging and endocrinological data at presentation and during follow-up were analysed. RESULTS: Headache and visual field defects were the most common presenting clinical features (64% and 55%, respectively). Ninety-four per cent of the tumours had an extrasellar component and 23% of them were associated with hydrocephalus. There was a significant difference in the recurrence-free survival rates between groups A-D [at 10 years: 100% (A), 100% (B), 38% (C) and 77% (D), P < 0.01], which persisted even when analysing patients operated after 1980. The median time of first recurrence was 2.5 years (range 0.5-36). The peri-operative mortality of the patients who had any type of neurosurgical intervention due to recurrence was higher than that observed after primary surgery (24%vs. 1.8%) (P < 0.01). The rate of re-accumulation of the cyst fluid was 58% during the first year in patients of group E, whereas none of the subjects of group F experienced such an event during their follow-up period. There was no reversal of pre-existing pituitary hormone deficits after any surgical intervention. The probabilities of GH, FSH/LH, ACTH, TSH deficiency and diabetes insipidus at the 10-year follow-up were 88%, 90%, 86%, 80% and 65%, respectively. After excluding the non-tumour-related deaths, the 10-year survival rate following presentation was 90%. Patients with recurrence had a significantly lower probability for survival compared with those without it (at 10 years: 70%vs. 99%, P < 0.01). At the 10-year follow-up the probability of the presence of major visual field defects was 48%, hyperphagia/obesity 39%, epilepsy 12% and hemi-/monoparesis 11%. In this large series no substantial differences in the outcome of tumours diagnosed during childhood or adult life were found. CONCLUSIONS: Craniopharyngiomas remain tumours associated with significant morbidity. Gross total removal provides favourable results in terms of recurrences. If this cannot be achieved safely, adjuvant radiotherapy is beneficial in preventing tumour re-growth. Childhood- and adult-onset lesions generally behave similarly.

Multiple endocrine neoplasia type 1 (MEN1) germline mutations in familial isolated primary hyperparathyroidism.

BACKGROUND: Familial isolated hyperparathyroidism (FIHP) is an autosomal dominant disorder characterized by uniglandular or multiglandular parathyroid tumours that occur in the absence of other endocrine tumours. The disorder may represent either an early stage of multiple endocrine neoplasia type 1 (MEN1), or an allelic variant of MEN1, or a distinct entity involving another locus. We have explored these possibilities in seven families in whom primary hyperparathyroidism occurred as the sole endocrinopathy. METHODS: Seven FIHP families were ascertained and venous blood samples obtained from 35 members (17 affected and 18 unaffected) for DNA sequence analysis of the MEN1 gene. The mean (+/- SD) follow-up period in the 17 affected members was 15.06 (+/- 8.83) years. RESULTS: Four heterozygous germline mutations of the MEN1 gene were identified. These consisted of two 4-bp intragenic deletions that would result in prematurely truncated proteins, and two missense (Asp153Val and Ala411Pro) mutations. Furthermore, analysis of parathyroid tumour DNA from one individual revealed a loss of the wild-type allele and retention of the mutant allele, consistent with Knudson's 'two-hit' model of hereditary cancer and a tumour suppressor role for MEN1 in FIHP. CONCLUSIONS: Our results provide further support for FIHP being a distinct allelic variant of MEN1, and an analysis of the 16 mutations reported to date indicate that FIHP is associated with a higher frequency of missense MEN1 mutations.

Coronary artery disease and dyslipidemia within Europe: genetic variants in lipid transport gene loci in German subjects with premature coronary artery disease.

Fifteen polymorphisms in six lipid transport genes were studied in a German population for relationships with dyslipidemia and coronary artery disease (CAD), to investigate a possible genetic basis for the marked differences in mortality rates from coronary heart disease within Europe. In other populations these polymorphisms have all been associated with CAD or with phenotypes known to predispose to CAD. The apoAI PstI polymorphism (P<0.005) and the lipoprotein lipase Ser(447)-Ter mutation (P<0.005) were associated with plasma triglyceride concentrations. Additionally, the apoAI PstI polymorphism (P<0.05), the apoB XbaI polymorphism (P<0.05) and apoE phenotypes (P<0.05) were associated with plasma cholesterol concentrations. However, none of the allele frequencies of the polymorphisms studied were related to the presence, or absence, of coronary artery disease. Associations between five polymorphisms representing four lipid transport gene loci and dyslipidemia were demonstrated in this German population. It is possible that predisposition to dyslipidemia in Germany involves a particular selection of polymorphic loci, which are different from those identified in other European countries.

Linear growth characteristics of congenitally GH-deficient infants from birth to one year of age.

Birth length has been reported to be either normal or reduced in infants with congenital GH deficiency (CGHD). We evaluated 46 infants with CGHD followed in a single regional medical center. All were born full term and had peak GH of less than 10 microg/liter after provocative stimulation. Length SD score at birth was normal but subsequently showed deceleration, at 6 months and 12 months of age, before GH treatment. The majority were delivered vaginally (83%), and delivery was uncomplicated in 61%. Four patients (9%) had breech vaginal delivery. Perinatal morbidities were found in 72% of infants and included jaundice (n = 17), hypoglycemia with or without seizure (n = 14), and hypoxemia (n = 5). Multiple pituitary hormone deficiencies were found in 85% of the subjects. Organic lesions were documented in all 22 subjects who had magnetic resonance imaging and in 4 of 11 subjects who had computed tomography scan. Only the hypoglycemic infants received early GH treatment. Growth data in hypoglycemic and normoglycemic CGHD infants were not significantly different. In our population, CGHD did not adversely affect fetal growth but is essential for normal linear growth during early infancy. Congenital developmental abnormalities in the hypothalamic-pituitary region are the most common cause of CGHD and are best diagnosed by an magnetic resonance imaging study.

Mobilization of patients after spinal surgery for acute spinal cord injury.

STUDY DESIGN: A retrospective review was conducted covering records of patients who underwent spinal surgery after acute spinal cord injury. OBJECTIVE: To study the relation between time of operation and mobilization of patients. SUMMARY OF BACKGROUND DATA: No such report has existed in the literature. METHODS: Reviews were conducted for the medical records of 102 consecutive patients with acute spinal cord injury admitted to the National Spinal Injuries Center whose spines had been stabilized surgically. The surgeries had been performed either in the National Spinal Injuries Center or in hospitals of the United Kingdom or Continental Europe not specialized in comprehensive care of spinal cord injury. For the patients in three groups, the date of operation and the date of mobilization were compared. The causes for delay in mobilization were identified. RESULTS: A trend of negative correlation was found between the mean number of days from injury to operation and the mean number of days from injury to mobilization. Conversely, a trend of positive correlation was found between the mean number of days from injury to admission or transfer to the National Spinal Injuries Center and the mean number of days from injury to mobilization. Long stay in bed was associated with complications. None of the patients in Group A stayed in bed longer than 77 days, whereas 13 patients in Groups B and C combined had a longer stay. The difference was statistically significant (P = 0.02, chi2). Eight of these patients had pressure sores. CONCLUSION: To ensure early mobilization, early spinal surgery must be supported by specialized comprehensive care.

Common genetic variants that relate to disorders of lipid transport in Spanish subjects with premature coronary artery disease.

Fifteen common polymorphic variants at six loci (apolipoproteins AI, B, CIII and E, hepatic lipase and lipoprotein lipase) involved in plasma lipid transport have been studied in 210 northern Spanish men, of whom 98 had proven coronary artery disease. The other 112 men were clinically free from coronary artery disease and acted as controls. The genotypes were investigated for relationships with plasma lipid and lipoprotein levels, as well as for the presence of coronary artery disease. As expected, the mean levels of plasma triacylglycerols (triglycerides) and lipoprotein (a) and the number of smokers were significantly higher in the disease group, and high-density lipoprotein (HDL)-cholesterol was significantly lower. Surprisingly, plasma cholesterol and low-density lipoprotein cholesterol were not different between the two groups. With regard to the common mutations, plasma triacylglycerol levels were related to the HindIII variants of lipoprotein lipase (P<0.05), to the apolipoprotein CIII variant (C3175G in exon 4) and to the apolipoprotein AI XmnI polymorphisms (P<0.05 and P<0.02 respectively). The apolipoprotein E variants were related to plasma cholesterol (P<0.05), HDL-cholesterol (P<0.02), plasma triacylglycerols (P<0.05) and the triacylglycerol/HDL ratio (P<0.01). Only the three-codon insertion/deletion variants of the apolipoprotein B signal peptide region discriminated between the two groups with or without arterial disease (P=0.02). The possible functional effects of these common mutations are discussed.

Radiation dose and diagnosticity of barium enema examinations by radiographers and radiologists: a comparative study.

With the current emphasis on the extension of the role of the radiographer, radiographers in some hospitals now undertake some of the procedures traditionally performed by radiologists. In the present study, dose-area product (DAP) measurements for over 1000 barium enema examinations performed by radiologists and radiographers were analysed and compared to ascertain whether there were significant differences in the radiation dose to the patient, depending on the category of staff performing the examination. All examinations were reported by a radiologist. The radiologist's reports were analysed against the known outcomes to compare the diagnosticity of the examination when carried out by the two categories of staff. The study shows that although radiographers are able to produce consistent diagnostic results, there is an increase in patient dose due to extra films taken for reporting, which may be difficult to justify. Measures for reducing the dose from this component of the examination were explored.

Comparison of final heights of growth hormone-treated vs. untreated children with idiopathic growth failure.

We measured adult heights (Ht) of 94 healthy GH-sufficient children (peak GH > 10 ng/mL, polyclonal RIA) whose Ht at presentation were more than 2 SD below the mean for chronological age, with normal weight-to-Ht ratios, normal body proportions, and pathologic growth velocity for chronological age. Group 1 (n 36, 6 females) received standardized doses (0.3 mg/kg x week) of GH (mean duration = 41 months), while group 2 (n = 58, 17 females) received no treatment. Our conclusion was that the mean final Ht SD score in the GH-treated group (-1.5) was significantly greater than in the untreated group (-2.1); P < .001. Genetic predisposition to short stature was evident in both groups: the midparental Ht SD score was -1.1 in the treated and -1.0 in the untreated group. Midparental Ht was met or exceeded by 42% of the GH-treated group but only 15% of the untreated group. Final Ht was not significantly different from predicted Ht, except from GH-treated girls, who exceeded their predicted Ht. Although the mean Ht gains (6.8 cm in girls and 3 cm in boys) were modest and variable, GH treatment provided significantly better Ht outcomes for the majority of children with idiopathic growth failure.

Common genetic variants of lipoprotein lipase that relate to lipid transport in patients with premature coronary artery disease.

Two common coding sequence mutations of lipoprotein lipase (serine447-ter, producing a carboxy terminal truncation; and asp9-asn variants) were studied in 329 Caucasian subjects, of whom 243 had angiographic features of premature atheroscelerosis (220 with coronary artery disease; 23 with coronary and peripheral artery disease). As expected, the mean levels of cholesterol, triglycerides, LDL-cholesterol, ApoB and Lp(a) were significantly higher in the arterial disease group than in the controls. HDL levels were lower in the patient group. With regard to the common mutations, plasma triglycerides and VLDL-triglycerides were lower in subjects possessing the Serine447-Ter mutation (p = 0.06 and < 0.05, respectively). When the lipid distributions were analysed by tertiles, the Ser447-Ter mutation was significantly less frequent in the highest tertiles for triglycerides (p < 0.02), and VLDL (p < 0.04). The Asp9-Asn substitution was significantly more frequent in the lowest tertiles for ApoAI (p = 0.05). Case-control analyses of genotypic distributions between the two groups with or without arterial disease did not show any significant differences. The possible functional effects of these common mutants of lipoprotein lipase are discussed.