Clinical evaluation of biomarkers in Gaucher disease

Novel or candidate biomarkers require thorough evaluation to establish their utility in a clinical setting. This paper describes an evaluation of several established enzyme markers of Gaucher disease and a newly-described chemokine, pulmonary and activation-regulated chemokine (PARC). The ability of the biomarkers to rank patients with Gaucher disease in order of disease severity and organ bulk, and to reflect changes in key clinical parameters in response to enzyme replacement therapy were evaluated. PARC concentrations were found to be reliably correlated with visceral disease and with key clinical responses to enzyme replacement in an unbiased manner. Unlike chitotriosidase and serum angiotensin-converting enzyme activity, genetic variation in serum PARC did not appear to influence its utility as a biomarker.
Conclusion: For each new candidate biomarker of lysosomal storage diseases, a similar clinical evaluation will be required, though the approach will need to be modified according to the clinical features and natural history of each disorder.     

Child Behaviour Checklist classification of behaviour disorder

Objective : The aim of this study was to determine the applicability of the published clinical cut-off scores of the Child Behaviour Checklist (CBCL) for the classification of behaviour disorders.
Methodology : Child Behaviour Checklists were obtained for 1342 subjects newly referred to the six major mental health centres in Melbourne. The normative community sample of 1002 7-, 12- and 15-year-olds was drawn from a school-based asthma prevalence study.
Results : The mean total problem T-score for the children referred to mental health centres was 67 and was above the clinical range for all age groups. Using referral to psychiatric services as the gold standard, the sensitivity and specificity of the CBCL using a cut-off of ≥ 60, was 77.4 and 83.2%, respectively. This compares favourably with the sensitivity of 68% and specificity of 82% for the American sample. Using a cut-off score of ≥ 63, the sensitivity was 70.5% and the specificity was 88.6%. The referred and community samples differed with respect to socio-economic status, family structure and mothers' level of education. Fifty-two per cent of the clinically referred children lived with both parents, compared with 89% of the community sample.
Conclusions : While there are some limitations to this study in terms of both the clinic and community sample, support is provided for the usefulness and applicability of the recommended CBCL cut-off scores in an Australian population.     

Roxatidine versus ranitidine in the treatment of duodenal ulcers: A randomized double-blind controlled multicentre study in Singapore

Roxatidine acetate, a new H₂ receptor antagonist, was compared with ranitidine in the treatment of duodenal ulcers in a double-blind multicentre study. Eighty-four patients with endoscopically proven duodenal ulcer were randomized to receive 150 mg roxatidine acetate or 300 mg ranitidine at bedtime. Repeat endoscopy was performed after 4 weeks (25–33 days) and if the ulcer had not healed, another endoscopy was performed after a further 4 weeks of treatment. Using per protocol analysis 73.6% of ulcers treated with roxatidine healed at 4 weeks compared to 72.2% of ulcers treated with ranitidine (P=NS). The healing rates at 8 weeks were 92% with roxatidine and 83.3% with ranitidine (P=NS). Using equivalence tests, the healing rate of roxatidine was found to be equivalent to that of ranitidine within a 20% region. Roxatidine users took significantly less antacids than ranitidine users (P < 0.05). There were no significant adverse effects due to roxatidine or ranitidine. Roxatidine is a safe effective drug in the treatment of duodenal ulcers with a healing rate comparable to that of ranitidine.     

Ultrasonic features of pyogenic liver abscesses

Ultrasonic features of 21 surgically confirmed pyogenic liver abscesses in 18 patients were analyzed. Typical lesions were round or ovoid with a discrete, irregular, echo-poor margin. The number and intensity of internal echoes and sound transmission were variable. Such lesions can be aspirated percutaneously for definitive preoperative diagnosis. Pyogenic liver abscesses appear to have more ragged walls and are less frequently elliptical or multilocular than abscesses elsewhere in the abdomen.     

Detection of carbamyl phosphate synthetase 1 deficiency using duodenal biopsy samples

The activity of urea cycle enzymes was assayed in duodenal biopsy specimens obtained from a female infant who presented with neonatal hyperammonaemia. All enzyme levels were normal except N-acetyl glutamate-dependent carbamyl phosphate synthetase 1 (CPS1) which was half the mean activity in normal control specimens. A similar deficiency of CPS1 was also shown in duodenal specimens from the patient's mother who became slightly symptomatic after relatively high protein meals and during pregnancy, and had spontaneously modified her diet to one with protein restriction. The patient is growing normally on a dietary regimen similar to that spontaneously adopted by her mother. Urea cycle enzyme activity in the duodenal biopsy material from the controls was similar to that found in the normal human liver and appears to have distinct advantages as a means of assaying for urea cycle defects in patients with hyperammonaemia and their relatives.     

Antibodies to diphtheria, tetanus and pertussis in infants before and after immunization with DTP (Triple Antigen) vaccine

Objective : To determine antibody levels to the Australian manufactured combined diphtheria, tetanus and pertussis (DTP) vaccine (Triple Antigen, CSL Ltd) in infante before and after their primary immunization course.
Methodology : Serosurvey (antibody prevalence study) in two groups: infants aged 5-9 weeks who had not received any immunizations ( n = 25), and infants aged 7-10 months who had received two ( n = 25) or three immunizations ( n = 57) with DTP, sampled from infants attending the Royal Children's Hospital, Melbourne, either as inpatients or outpatients between February and April 1993. The immunization history for each infant was determined from hospital records, the parent-held child health record, or the local council or family doctor who immunized the infant.
Results : Enzyme immunoassay (EIA) of antibodies to diphtheria and tetanus showed all infants to have adequate protective levels after two or three vaccinations (£0.01 IU/mL). All subjects who had received all three DTP vaccinations had detectable antibody to at least one pertussis antigen. Antibodies to the pertussis antigens filamentous haemagglutinin and pertussigen (pertussis toxin) were comparable to levels determined for whole cell pertussis vaccines used elsewhere in the world. EIA-determined antibodies to pertussis agglutinogen type 2 and agglutinogen type 3 showed substantially higher geometric mean titres when results for pre-immunization and post-immunization subjects were compared.
Conclusions : These data show that the Australian manufactured DTP vaccine has immunogenic properties similar to those of vaccines used elsewhere, and that antibody concentrations following immunization are at levels consistent with efficacy.