Treasuring the past. Interview by Teresa O'Connor.
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Biomedical subjects
Publications and source records attributed to M Burgess.
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BACKGROUND: Case reports suggest that recurrent nightmares are alleviated by behavioural treatment. We have administered such treatment to a client by post. METHOD: The frequency of nightmares was recorded by the client before and during treatment, and at one and six months follow-up. Nightmare problem and target scales, and treatment expectation were recorded at the end of each period. Treatment was by rehearsal relief, self-administered using written instructions. RESULTS: A reduction in nightmare frequency from 5.5 per week in the baseline period to an average of one per week resulted after treatment. CONCLUSIONS: The client's chronic nightmares were lastingly relieved after self-administered exposure treatment. A controlled trial is underway.
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Precocious puberty can be caused by hormonally active tumours, which may arise intracranially. Treatment of these intracranial lesions traditionally involves biopsy and radiotherapy. Chemotherapy has been used recently, although radiotherapy has been given irrespective of the response to chemotherapy. We report a case of precocious puberty in an 8 year old boy due to a malignant intracranial germ cell tumour. Although one could speculate that he was cured by such combined modality therapy, the patient was left with several long-term problems. Radiotherapy was a major cause of these complications. Radiotherapy is now thought unnecessary for most extracranial germ cell tumours, as chemotherapy alone is curative in most patients. Therefore it seems appropriate to consider the elimination of radiotherapy for patients with intracranial disease.
Outbreaks of vaccine preventable infections have focused attention on 'missed opportunities' for immunizing children. The immunization status of 520 consecutive children attending Casualty during a 10 day period was studied. Only 70% of children had received their diphtheria, tetanus, pertussis (DTP) and poliomyelitis immunization at the appropriate time, 13% had completed the schedule later than recommended and 17% had immunizations overdue by 4 weeks or more. For measles (mumps/rubella) vaccine (MM or MMR) 75% were up to date, 10% were given late and 15% were overdue. A subset of 171 families was interviewed to evaluate factors affecting compliance. Families possessing a Social Security 'Health Care Card', whose father was unemployed, who spoke poor English or who had lived in Australia for 5 years or less were significantly more likely (P < 0.02) to be inadequately immunized. There were 84 children whose immunization was overdue and who were well enough to be immunized. The parents of 70 (83%) of these 84 said that they would agree to 'on the spot' immunization if it were available; 14 (17%) parents refused, the commonest reason for refusal being that the parents felt that the child was too sick at the time to be immunized.
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Two children, aged 15 months and 3 years, developed abdominal distension following proven Cryptosporidium enteritis. Both required readmission to hospital and both improved rapidly, one spontaneously and one with the help of an enema. The association of abdominal distension and Cryptosporidium infection has not been described previously.
DMDR, a daunorubicin derivative with a higher therapeutic index and lower cardiotoxicity than either the parent drug or doxorubicin, is active when given PO in experimental animals. We studied its pharmacokinetics in ten patients receiving DMDR IV or PO or IV and PO sequentially at 10-12.5 mg/m2. DMDR and its metabolites were quantified by high-performance liquid chromatography and fluorometry. In nine patients who received DMDR IV the unchanged drug disappeared from the plasma biphasically with a mean terminal half-life of 27.0 +/- 5.5 h, an apparent volume of distribution of 63.9 +/- 12.61 kg-1, and a total clearance of 1.9 +/- 0.41 kg-1 h-1. In 24 h only 5.1% +/- 1.1% of the dose was excreted in the urine. In comparison, in 19 studies the plasma half-life of DMDR given PO was 34.8 +/- 6.7 h, 2.3% +/- 1.3% was excreted in the urine in 24 h, and the maximum plasma drug concentration was reached in about 1 h. The bioavailability of DMDR given PO was about 39% according to comparison of the areas under the plasma DMDR concentration versus time curves for the two routes, but 45% according to comparison of the 24-h cumulative urinary excretion rates. In one patient with severe liver dysfunction following oral administration, the plasma DMDR half-life was 56.8 h, more than twice the average length. By either route, the drug was quickly metabolized to one major metabolite, DMDR-ol. The plasma half-life of DMDR-ol was 72.5 +/- 24.7 h, or 35.7 +/- 7.4 when DMDR was administered IV or PO. In the plasma, DMDR-ol always exceeded DMDR in concentration. Moreover, the 24 h cumulative urinary excretion of DMDR-ol as a percentage of the dose of DMDR administered was 7.8 following IV and 7.4 following PO administration.
From January 1980 to June 1984, 70 patients with metastatic carcinoma of unknown primary treated with combination chemotherapy were analyzed for prognostic factors influencing objective response and survival. Suspicious germ-cell tumors and neuroendocrine tumors were excluded since patients with these malignancies tend to live longer than those with metastatic carcinoma of unknown primary. Objective response rate to combination chemotherapy was 28%. Median survival of all patients responding to combination chemotherapy was better than those not responding (16 v 3 months). In patients with good performance status, median survival was longer in responders than nonresponding patients (17 v 7 months). External lymph nodes or subcutaneous disease as the only site of disease and good performance status favorably influenced both objective response and survival, while the number of different metastatic sites favorably influenced only survival. Neutropenia and thrombocytopenia were appreciable but not fatal or a great cause of morbidity in those with good performance status. Thus, patients with metastatic carcinoma of unknown primary with good performance status or only external nodes or subcutaneous disease should be treated with combination chemotherapy regardless of age, histology, or number of different metastatic sites of disease.
Clinical pharmacokinetics of homoharringtonine (HHT) were studied in eight patients who received uniformly labeled HHT at 3-4 mg/m2 (150 mu Ci) by continuous 6-hour infusion. The drug and metabolites were quantified by radiochemical and high-performance liquid chromatographic techniques. Computerized nonlinear least-square regression and curve stripping were used to characterize HHT and total [3H]HHT equivalent pharmacokinetics. Unchanged HHT in the plasma declined biphasically, with an alpha-half-life of 0.5 +/- 0.1 hours and a beta-half-life of 9.3 +/- 1.4 hours. The total clearance of HHT was 177.4 +/- 27.7 ml X hour-1 X kg-1, and the apparent volume of distribution, estimated from the area under the drug concentration versus time curve, was 2.4 +/- 0.4 L X kg-1. Correspondingly, the total [3H]HHT equivalent disappeared from the plasma in a triphasic manner. Compared with the pharmacokinetic parameters of unchanged HHT, the terminal half-life of total 3H was 67.5 +/- 7.5 hours, 7.4 times longer; the total clearance was 30.9 +/- 3.1 ml X hour-1 X kg-1, 5.5 times slower; but the volume of distribution by area was 2.7 +/- 0.1 L X kg-1, nearly the same. The 72-hour cumulative urinary excretion of total tritium was 28.2% of the administered dose and only 38.3% of this resided in unchanged HHT. Thus, urinary excretion was not a major route of elimination of HHT. Moreover, HHT underwent extensive metabolism; one major and two minor unidentified products were detected in both plasma and urine.
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