Improving Prenatal Diagnosis of Coarctation of the Aorta

Background

The purpose of the study was to evaluate the association between fetal echocardiographic measurements and the need for intervention (primary coarctation repair, staged coarctation repair, or catheter intervention) in prenatally diagnosed coarctation of the aorta.

A double-blind, multicentre, placebo-controlled study of tiludronate in Paget's disease of bone.

A multicentre, randomised, placebo-controlled, dose-ranging study was conducted to investigate the therapeutic activity and sustained efficacy of tiludronate (200 mg, 400 mg and 600 mg once daily) taken orally for 12 weeks in patients with Paget''s disease. Serum alkaline phosphatase concentrations were compared with baseline at weeks 12 and 24; treatment success was defined as a 50% reduction compared with baseline. Changes in the hydroxyproline: creatinine ratio were also measured. Pain was assessed using the Huskisson Visual Analogue Scale and by questionnaire. Patients completing at least 11 weeks of treatment were followed-up 18 months later by postal questionnaire. Significantly greater numbers of patients in the tiludronate groups successfully responded to treatment compared with the placebo group. A dose-response was observed; the percentage of patients responding to treatment being 31% (200 mg), 52% (400 mg) and 82% (600 mg) at week 12 and 45% (200 mg), 70% (400 mg) and 82% (600 mg) at week 24. Tiludronate treatment also significantly reduced hydroxyproline: creatinine ratios compared with placebo, again showing a dose response. Dose-related gastrointestinal symptoms were the commonest adverse events, occurring in 2.4%, 11.0%, 5.5% and 18.9% of patients receiving placebo and tiludronate 200, 400 and 600 mg daily, respectively. The response to oral tiludronate was sustained for more than 18 months in some patients and there was evidence of a reduction in the longer term complications of the disease. These results show that oral tiludronate is an effective, well-tolerated treatment for Paget''s disease; the 400 mg once daily dose appears to offer the optimum balance of efficacy and tolerance.     

Neutrophil Bactericidal Function in Diabetes Mellitus: Evidence for Association with Blood Glucose Control

Neutrophil bactericidal activity was assessed in patients with type 1 (n=45) and Type 2 diabetes mellitus (n=68) and non-diabetic control subjects (n=40) by measurement of whole blood chemiluminescence. Though chemiluminescence values tended to be highest in the non-diabetic subjects these differences were not statistically significant (mean ± SD) (2.73 ± 1.65 mV (controls), 2.33 ± 1.41 mV (Type 1 diabetes) and 2.38 ± 1.12 mV (Type 2 diabetes), F=1.12, p=0.33). Significant negative correlations were evident, however, in patients with both Type 1 and Type 2 diabetes between chemiluminescence and glycated haemoglobin (r_s=-0.35, p=0.005 (Type 1), r_s=-0.45, p=0.002 (Type 2), fructosamine (r_s=-0.36, p=0.003 (Type 1), r_s=-0.42, p=0.004 (Type 2)), and random blood glucose (r_s=-0.25, p=0.04 (Type 1), r_s=-0.48, p=0.001 (Type 2)). Changes in whole blood chemiluminescence in a further group of 10 patients with Type 2 diabetes mellitus commenced on insulin therapy were followed for 21 days. Serum fructosamine concentrations fell significantly over this time (524 ± 58 μmol l^?1 to 405 ± 47 μmol l^?1, p<0.001), however, although chemiluminescence values tended to rise these changes were not statistically significant (1.01 ± 0.38 mV to 1.60 ± 0.91 mV, S=4.24, df=5, p=0.52). These results suggest that impaired neutrophil bactericidal function is associated with poor blood glucose control. While it is likely that neutrophil bactericidal function will improve as blood glucose control improves, further studies are required both to confirm this and to demonstrate a reduction in the incidence of clinical bacterial infection.     

Benign intracranial hypertension and recombinant growth hormone therapy in Australia and New Zealand

Benign intracranial hypertension (BIH) is reported in three children from Australia and one from New Zealand, who were being treated with recombinant human growth hormone (rhGH). Three males and one female, aged between 10.5 and 14.2 y, developed intracranial hypertension within 2 weeks to 3 months of starting treatment. A national database, OZGROW, has been prospectively collecting data on all 3332 children treated with rhGH in Australia and New Zealand from January 1986 to 1996. The incidence of BIH in children treated with growth hormone (GH) is small, 1.2 per 1000 cases overall, but appears to be greater with biochemical GHD (<10IUml ^-1), i.e. 6.5/1000 (3 in 465 cases), relative risk 18.4, 95% confidence interval 1.9-176.1, than in all other children on the database. The incidence in patients with Turner's syndrome was 2.3/1000 (1 in 428 cases). No cases in patients with partial GHD (10–20 IUml ^-1) or chronic renal failure were identified. Possible causative mechanisms are discussed. The authors'practice is now to start GH replacement at less than the usual recommended dose of 14IUm-² week^-1 in those children considered to be at high risk of developing BIH. Ophthalmological evaluation is recommended for children before and during the first few months following commencement of rhGH therapy and is mandatory in the event of peripheral or facial oedema, persistent headaches, vomiting or visual symptoms. The absence of papilledema does not exclude the diagnosis.     

Biologic variation of common hematologic laboratory quantities in the elderly

Analytic, within-subject, and between-subject biologic variations were estimated for leukocytes, erythrocytes, hemoglobin, hematocrit, mean cell volume (MCV), mean cell hemoglobin (MCH), mean cell hemoglobin content (MCHC), platelets, and a three-component differential count (lymphocytes, monocytes, and granulocytes in terms of both concentration and percentage of leukocytes) in cohorts of 12 male and 12 female healthy elderly subjects. The assays were performed with an Ortho ELT-800 automated analyzer. The estimates of within-subject biologic variation were similar to published data on young subjects, indicating that this aspect of homeostasis is not compromised in the elderly. The data were used to derive objective analytic goals; goals were surpassed except for assays of erythrocytes, hematocrit, and the derived MCV, MCH, and MCHC. The changes required for serial results to be significantly different were determined and found to be generally valid because most quantities have no heterogeneity of within-subject variation. All quantities had significant individuality; in consequence, conventional population-based reference values are of limited utility, and screening using reference limits will not detect latent or early disease in many subjects.