Three-year experience with access to nationally funded growth hormone (GH) replacement for GH-deficient adults.

OBJECTIVE: Treatment of growth hormone (GH)-deficient adults with GH has been shown to improve a range of metabolic abnormalities and enhance quality of life. However, the results of access to nationally funded treatment have not been reported. DESIGN: Retrospective case series auditing nationally funded treatment of defined GH-deficient adults in New Zealand, with carefully designed entry and exit criteria overseen by a panel of endocrinologists. PATIENTS: Applications for 201 patients were assessed and 191 approved for funded treatment over the initial 3 years since inception. The majority had GH deficiency following treatment of pituitary adenomas or tumours adjacent to the pituitary. RESULTS: After an initial 9-month treatment period using serum IGF-I measurements to adjust GH dosing, all patients reported a significant improvement in quality of life (QoL) score on the QoL-AGHDA(®) instrument (baseline (95%CI) 19 (18-21), 9 months 6 (5-7.5)), and mean serum IGF-I SD scores rose from -3 to zero. Mean waist circumference decreased significantly by 2.8 ± 0.6 cm. The mean maintenance GH dose after 9 months of treatment was 0.39 mg/day. After 3 years, 17% of patients had stopped treatment, and all of the remaining patients maintained the improvements seen at 9 months of treatment. CONCLUSION: Carefully designed access to nationally funded GH replacement in GH-deficient adults was associated with a significant improvement in quality of life over a 3-year period with mean daily GH doses lower than in the majority of previously reported studies.

The annual reports of Local Research Ethics Committees.

Each Local Research Ethics Committee (LREC) is expected to produce an annual report for its establishing authority. Reports from 145 LRECs were examined with regard to (a) whether the committees were working within the terms of the most recent guidelines from the Department of Health and (b) observations on the role of LRECs with particular reference to accountability. Most LRECs had produced a report, although their length varied greatly. Most reports showed how seriously the committee took its task. Most committees met many of the guidelines; for example, almost all had two or more lay-members. The guideline most frequently not met was that committees should have no more than 12 members. Many committees review very large numbers of projects (maximum 351). Approximately two-thirds provide details in the annual report of individual project titles, their author and the committee decision; all reports should contain this information. Although it may in fact happen more generally, only 23 per cent of the reports referred to any form of monitoring of the eventual outcome of the research. A significant issue to arise from the reports is the extent to which the framework for the operation of LRECs has been confused by the development of the purchaser-provider split. The paper concludes with suggestions for remedying the situation.

The acute abdomen in emergency with Hypercard.

A non-sequential Bayesian program for diagnosing acute abdominal pain was developed using an Amdahl mainframe accessed by a Texas Instrument remote terminal. Transferring the program to a MacIntosh SE/30 using hypercard was attended by increased utilisation from 15 to 44%.

Severe type III von Willebrand's disease caused by deletion of exon 42 of the von Willebrand factor gene: family studies that identify carriers of the condition and a compound heterozygous individual.

Southern blotting was performed with cDNA probes for the human von Willebrand factor (vWF) gene on six patients with severe type III von Willebrand's disease (vWD). A partial deletion in the 3' end of the vWF gene was demonstrated in one individual whose parents were related and who had an alloantibody inhibitor to vWF. A resulting novel 2.0-kilobase (kb) EcoRI fragment was used for carrier detection within the patient's family, and seven carriers of this recessive trait were identified. Of the six tested, five had normal or only slightly reduced levels of vWF antigen, but with generally higher levels of factor VIII. The sixth carrier had moderately severe vWD and it is proposed that this patient is heterozygous for the defective vWF gene and a second recessive vWF defect. The novel 2.0-kb EcoRI restriction fragment was cloned and sequenced, and compared with that of the corresponding normal 4.2-kb EcoRI fragment that includes exons 41 and 42 of the vWF gene. A deletion of 2,320 base pairs (bp) which included exon 42, was identified and a novel 182-bp insert was found between the breakpoints. This insert was detected by polymerase chain reaction amplification both in the patient's DNA and in his carrier relatives.

An audit of a cervical smear screening programme.

An audit of a computer based screening and recall programme in a Wellington group general practice is reported (practice population 13,866). The records of all women aged between 20 and 59 years (4133 women) were checked to determine if they had had a cervical smear test in the previous two years. A random sample of women who had a cervical smear result recorded in the notes (107 women called "responders") showed that 71% gave "familiarity with the family doctor" and "acting in response to a recall letter" as reasons for choosing the place of their last smear. Satisfaction with the service was indicated by 95% of these women stating they would have their next smear at the medical centre. In the audit of all the records, a group of 667 women who had been sent a letter inviting them to have a smear done and who had apparently declined the procedure was identified (called "nonresponders"). A random sample of this group (168 women) was taken and an attempt made to interview them. In fact only 38 women could be identified as requiring a smear and even if those who refused to be interviewed (13) and those unable to be contacted (23) are added, then less than half of this sample were "true nonresponders". This suggests that the percentage of women in the practice who have been offered a smear and have refused to have one is less than 8%.

Carrier detection in 50 haemophilia A kindred by means of three intragenic and two extragenic restriction fragment length polymorphisms.

Carrier detection was attempted in 50 haemophilia A kindred by means of restriction fragment length polymorphism (RFLP) analysis using two linked and three intragenic probes. The sample comprised 330 individuals including 70 haemophiliacs, 45 obligate carriers and 100 possible carriers. Non-related haplotypes contained within the sample group were used to tabulate the intragenic RFLP allele frequencies. The linkage disequilibrium existing between the XbaI and Bc1I RFLP was shown to be less than previously reported, such that 69% of women are informative for at least one of these two polymorphisms. 36 women were subsequently diagnosed as carriers and 37 as being normal: in 52 of these, diagnosis was based either on intragenic RFLPs or linked RFLP plus strong phenotypic data, and was considered to be unequivocal; in the remaining 21, diagnosis was based on linked RFLPs alone and was considered to be probabilistic, with a 5-10% possible error rate. 27 of the possible carriers, either from families with sporadic haemophilia or from families where missing members precluded haplotype analysis, remained unassigned. 72% of the obligate carriers and firmly diagnosed carriers were heterozygous and phase known for at least one intragenic RFLP, whereas 6% were uninformative for the RFLPs for which they were examined. In 54 informative meioses, three recombinations between the factor VIII locus and the DX13 and/or ST14 loci were observed, giving a recombination rate of 5.5%. 15 prenatal diagnoses were carried out. Of the 11 male fetuses, six were shown to be affected and five to be normal. In three of four prenatal diagnoses where only a linked RFLP was informative, the result was confirmed by fetoscopy, fetal blood sampling, and factor VIII assay.

Does family history of breast cancer improve survival among patients with breast cancer?

Overall cancer mortality to December 1985 among 291 patients whose breast cancer was diagnosed between 1971 and 1974 and who were interviewed shortly after diagnosis was 39.9% (116 deaths). In this study population a positive maternal family history was strongly associated with breast cancer: The odds ratio for patients versus controls of having a mother with breast cancer was 3.32 (95% confidence limits 1.64 and 6.72); the odds ratio of having a mother, sister, or maternal aunt with breast cancer was 1.92 (95% confidence limits 1.27 and 2.91). However, family history was not associated with stage at diagnosis, which is the most important survival factor (53.6% of patients with a family history and 51.7% without were at a local stage at diagnosis). Survival was better, although not significantly so, among women with maternal relatives with breast cancer. The relative risk of dying of cancer, adjusted for confounding factors, was 1.40 for women without versus with a family history; the difference in survival was not statistically significant.

Medical aspects of Aboriginal health.

The pattern of disease in the Australian Aboriginal population as a whole, and the manifestations of this pattern in the Aboriginal individual, are atypical for Australia in general. This requires some adjustment of the doctor's approach to diagnosis, immediate patient care and family medicine management when dealing with Aboriginal patients.