Selective uptake of hematoporphyrin derivative into human cerebral glioma

The uptake of hematoporphyrin derivative (HpD) into human cerebral glioma was measured using a porphyrin extraction technique. Patients with cerebral glioma were injected with HpD at a dose of 5 mg/kg body weight 24 hours before surgery and photoradiation therapy (PRT). Biopsies of tumor, and where possible, adjacent brain and normal brain were taken for analysis of HpD uptake. HpD was selectively localized into all grades of glioma, and there was a direct correlation between the grade of glioma and HpD level in the tumor. The levels were highest in glioblastoma multiforme (mean uptake of 5.9 micrograms of HpD/g of tumor wet weight) and lower in the intermediate-grade anaplastic astrocytoma (mean uptake of 2.4 micrograms/g of tumor) and the low-grade astrocytoma (1.6 micrograms/g of tumor). Uptake into normal brain tissue taken from HpD-sensitized patients was 0.2 microgram/g. HpD was also localized into the "brain adjacent to tumor" region. The selective uptake into the low-grade glioma suggests that PRT may be of use as an adjuvant therapy in these tumors and the detection of HpD in this region indicates that PRT may control the spread of tumor infiltrating into the adjacent normal brain.     

Simplified method of heterotopic cardiac transplantation for left ventricular assist

A method of heterotopic cardiac transplantation has been developed which is performed through a left thoracotomy and requires only two vascular anastomoses. Systemic heparinization and cardiopulmonary bypass are not necessary. Preliminary experiments demonstrated that this heterotopic transplant technique was effective for left ventricular assist; in some experiments, a multimode atrioventricular programmable pacemaker was used to provide sequential pacing for "counterpulsation." This technique or similar techniques may have potential clinical benefit for patients with intractable left ventricular failure.     

Flavone acetic acid: a nonlinear pharmacokinetic model

Summary Flavone acetic acid pharmacokinetics were studied in 31 patients in a phase I clinical trial. The drug was given by i.v. infusions over 1, 1.5, 3, and 6 h at doses ranging from 0.5 to 6.4 g/m². The pharmacokinetic parameters were determined according to a nonlinear model including Michaelis-Menten-type kinetics. The mean elimination half-life is 4.8 h and the mean volume of distribution of the central compartment, 7.61. Our model predicted a maximal tolerated dose (MTD) of 11.1 g/m² on the basis of the therapeutic window concept, very close to the clinically observed MTD of 10 g/m². This model is also operational when different protocols of inoculation are considered, such as a divided-dose schedule vs a unique infusion, and indicates that, at the MTD, injections should be made every 72 h to avoid drug accumulation.     

Role divergence and complexity in gerontological home care.

This study documents high levels of role complexity and functional overlap in the field of home health care. Personnel perform a wide range of "professional/organizational" and "community/familial" service functions though the emphasis is on the delivery of a battery of pseudo family-like tasks. The importance of a familial orientation does not significantly decline when controlling for length of employment or organizational rationality. Role orientation is, however, significantly associated with a worker's chronological age. Results lead to program planning recommendations meant to influence staff training paradigms in home health care.     

In vitro metabolism studies on oxamniquine and related compounds by chiral liquid chromatography

A previously developed method based on alpha 1-acid glycoprotein for the resolution of the enantiomers of the Pfizer antischistosomal drug oxamniquine was used to examine possible enantioselectivity in the in vitro microsomal hydroxylation of a metabolic precursor, UK-3883, but was found to be limited by the poor operational stability of the analytical column ("EnantioPac") employed. As an alternative approach, a "Pirkle" covalently-bonded dinitrobenzoyl leucine column was used, with simple precolumn solute derivatization to the carbamate to improve chromatographic performance. The method allowed preliminary examination of the stereochemistry of the in vitro biotransformation, hydroxylation of UK-3883 to oxaminquine, which yielded evidence for substrate enantioselectivity in favour of the dextrorotatory enantiomer of UK-3883.     

Phase I clinical and pharmacokinetic study of LY 195448

Summary LY 195448 is a phenethanolamine that has shown anti-tumour activity in a range of murine tumour models, although its mechanism of action is unknown. Pre-clinical studies have indicated the absence of standard side effects such as myelosuppression and gastrointestinal toxicity. The present phase I trial was carried out in nine patients at doses ranging up to 133 mg/m². The major toxicities up to that dose were mild, reversible hypotension, tachycardia and tremor. No haematological or biochemical toxicity was observed. Murine pharmacokinetics were assessed at a dose level that was effective in experimental tumours and compared with human pharmacokinetic parameters derived from this study. The results indicated the clinical possibility of reaching peak drug levels associated with experimental activity. However, no responses were seen at the doses used. This study was terminated prior to its completion due to an unexplained loss of activity against murine tumours since September 1987. No significant loss of the in vitro anti-mitotic activity originally reported by Boder et al. [3] was observed. Possible reasons for the apparent loss of in vivo activity have been intensively investigated, but no cause has been determined. Therefore, clinical trials with LY 195448 have been discontinued.     

Sodium stibogluconate (Pentostam) overdose during treatment of American cutaneous leishmaniasis.

A 27-year-old woman who acquired cutaneous leishmaniasis in Central America was inadvertently treated with 10 times the intended daily dose of the pentavalent antimonial compound sodium stibogluconate (Pentostam): 8500 mg (143 mg/kg) instead of 850 mg. The patient felt "wiped out" during the 4-h infusion of the drug. After the mistake in dosing was discovered, she was vigorously hydrated and carefully monitored in an intensive care unit for greater than 48 h. Her vital signs were stable, and no arrhythmias were noted. Her alanine aminotransferase level rose briefly to 2.4 times the upper limit of normal, and her white blood cell count briefly fell 43% to a low of 3700/microliter. Her skin lesions subsequently healed without further therapy. Although sodium stibogluconate has been associated with a variety of side effects, in this case, a single high dose of the drug was tolerated without serious toxicity.     

The first of earthly blessings, independence. Development of a service for the severely physically disabled

Over the past six or seven years Basingstoke and North Hampshire HA has invested considerable effort in pioneering a particular approach to the provision of care and support to the extremely physically disabled. Charles Kaye describes the development of the service and pursuit of quality assurance.