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.     

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.     

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.     

Catch-up growth up to ten years of age in children born very preterm or with very low birth weight

Background  

Improved survival due to advances in neonatal care has brought issues such as postnatal growth and development more to the focus of our attention. Most studies report stunting in children born very preterm and/or small for gestational age. In this article we study the growth pattern of these children and aim to identify factors associated with postnatal catch-up growth.     

Prevention of recurrence and prolonged survival in primary central nervous system lymphoma (PCNSL) patients treated with adjuvant high-dose methylprednisolone

Five patients at risk for primary central nervous system lymphoma (PCNSL) recurrence were treated with high-dose methylprednisolone (HDMP) to prevent 'trafficking' of malignant lymphocytes into the central nervous system (CNS). HDMP was chosen because of its ability to stabilize the 'blood brain barrier (BBB)'. Three men with newly diagnosed PCNSL, ages 62, 76 and 78y, whose survival was projected to be 6.6 months, began treatment after achieving complete response (CR) to initial radiation therapy alone and survived 27, 37 and 59 months after treatment. In none was death from recurrent disease in CNS but one patient did die of systemic non-Hodgkin's lymphoma (NHL) five years after PCNSL diagnosis. A 20 y old man was treated with HDMP after successful combined modality therapy and is alive 75+ months after initial diagnosis without evidence of disease recurrence. A 34 y old man relapsed after combined modality initial treatment and failed to respond to HDMP when treatment was begun after unsuccessful salvage therapy; he died of disease 12 months after initial diagnosis. There were no treatment complications. The promising results in this pilot study from the basis for a North Central Cancer Treatment Group (NCCTG) 96-73-51, a Phase 2 clinical trial of brain radiotherapy and HDMP for PCNSL patients 70y of age and older, a group of patients at high risk for toxicity from intensive combined modality therapy.