Membrane-disorganizing property of polymyxin B nonapeptide

The possibility of improving the antibacterial activities of drugs normally excluded by Gram-negative bacteria with polymyxin B nonapeptide (PMBN) has been explored. In vitro, PMBN rendered clindamycin, erythromycin, novobiocin, rifampicin and vancomycin very active against a number of Gram-negative enteric bacteria. The drug also sensitized the previously resistant bacterial strains to human, mouse or guinea pig serum. However, parenterally administered PMBN failed to influence bacterial growth in chambers implanted into mice and guinea pigs. It was also ineffective in experimental septicaemia at a dose of up to 200 mg/kg or when combined with antibiotics with which it interacted synergistically in vitro.     

Influence of overweight and obesity on physician costs in adolescents and adults in Ontario, Canada

The study purpose was to perform an obesity cost-of-illness analysis for individuals living in the province of Ontario, Canada. The participants consisted of a representative sample of 25 038 adults and 2440 adolescents (aged 12–17 years) who participated in the 2000/2001 Canadian Community Health Survey (CCHS). The CCHS data set includes measures of body mass index (BMI) (classified as normal weight, overweight or obese) and relevant covariates (age, income, smoking, alcohol, physical activity). The CCHS data set was linked to the Ontario Health Insurance Plan providers' database to obtain physician costs for 2002–2003. A two-part modelling approach was used to calculate and compare the average annual physician cost according to BMI. After adjusting for the covariates, physician costs were not significantly higher in overweight men and women compared with those with a normal weight. Physician costs were 14.7% higher in obese men and 18.2% higher in obese women than in men and women with a normal weight. Average physician costs were comparable in normal-weight and overweight/obese adolescents ($233 per year in both groups). Because Ontario operates a publicly funded healthcare system, the findings of this study have relevance for other provinces/states and countries that operate similar healthcare systems.     

Subcranial anterior skull base dural repair with galeal frontalis flap.

The pericranial flap has been widely used to repair surgically created anterior skull base defects during craniofacial resection. This report describes a technique of subcranial dural repair with a galeal frontalis flap after resection of an ethmoidal adenoid cystic carcinoma.     

Pion therapy at TRIUMF. Treatment results for astrocytoma grades 3 and 4: a pilot study

At TRIUMF, (located on the University of B.C. Campus), 53 patients with supratentorial astrocytoma grades 3 and 4 were treated with pions between 1982 and 1985. A 3-dimensional spot-scanning treatment technique has proven to be practical. The accuracy of the beam alignment system used for treatment was reproducible daily within 2 mm. Low pion flux has hindered optimal beam shaping but this will soon be remedied as flux improves. The overall median survival observed (53 patients) is 262 days from date of first radiation treatment. Younger (less than 49 years) patients have significantly better survival than older (greater than 50 years) patients (p = 0.001). From a base line dose of 40 Gy photons whole brain and 17.5 Gy pion boost, doses were escalated to 33 Gy pions localised to the primary tumour and the median survival improved from 198 to 436 days. Survival curves for patients treated with localised pion techniques to doses above 30 Gy are significantly better than for those treated with schedules of pions mixed with photons (p = 0.04). It appears that optimal pion dose for brain tumours is 33 Gy minimum with a possible maximum of 36 Gy and doses delivered in 15 fractions in 3 weeks. Requirements for future trials are discussed.     

Inhibition of carrageenan induced inflammation in the rat knee joint by substance P antagonist.

The pathophysiology of acute joint inflammation remains unclear. Evidence is available to suggest a neurally mediated component to the inflammatory process. Acute joint inflammation in the rat knee, induced by intra-articular injection of 2% carrageenan, was reduced by 44% in animals whose knee had previously been injected with 1% capsaicin, while chronic joint denervation produced a 37% reduction. These results indicate a significant neurogenic component in this model of acute joint inflammation. Substance P may be the mediator of this response as intra-articular injection of this agent provoked an acute inflammatory response. Pretreatment of the test knee with the substance P antagonist d-Pro4,d-Trp7 9 10-SP(4-11), however, resulted in a 93% reduction of the inflammatory response to carrageenan. This unexpectedly large effect suggests that this substance P antagonist blocks both neurogenic and non-neurogenic mediators of inflammation. Sympathetic efferent fibres innervating the knee joint were not found to contribute to the neurogenic component of the inflammatory process.     

In vivo use of a radioiodinated somatostatin analogue: dynamics, metabolism, and binding to somatostatin receptor-positive tumors in man.

Somatostatin analogues, labeled with gamma-emitting radionuclides, are of potential value in the localization of somatostatin receptor-positive tumors with gamma camera imaging. We investigated the application in man of a radioiodinated analogue of somatostatin, 123I-Tyr-3-octreotide, which has similar biologic characteristics as the native peptide. The radiopharmaceutical is cleared rapidly from the circulation (up to 85% of the dose after 10 min) mainly by the liver. Liver radioactivity is rapidly excreted into the biliary system. Until 3 hr after injection, radioactivity in the circulation is mainly in the form of 123I-Tyr-3-octreotide. Thereafter, plasma samples contain increasing proportions of free iodide. Similarly, during the first hours after injection, radioactivity in the urine exists mainly in the form of the unchanged peptide. Thereafter, a progressive increase in radioiodide excretion is observed, indicating degradation of the radiopharmaceutical in vivo. Fecal excretion of radioactivity amounts to only a few percent of the dose. The calculated median effective dose equivalent is comparable with values for applications of other 123I-radiopharmaceuticals (0.019 mSv/MBq).     

Area method for the estimation of partition coefficients for physiological pharmacokinetic models

A new technique, the area method, is derived for the determination of partition coefficients for both blood-flow limited and membrane limited physiological pharmacokinetic models. This method was compared to a standard technique by Monte Carlo simulation. Partition coefficients were calculated for the blood-flow limited case for both eliminating and noneliminating organs. It was found that the area method compared favorably to a standard technique and was less prone to error. This may be attributed to the more subjective interpretation as to which data points are included in the terminal phase, since the standard method relies on the accurate determination of the terminal slope for the calculation of partition coefficients. Both methods are satisfactory for the calculation of partition coefficients with the area method being more accurate and precise.     

Cerebral radionecrosis: is surgery necessary?

Seven patients with cerebral necrosis after radiotherapy for carcinoma of the nasopharynx are presented. The clinical features included seizures and a varying degree of intellectual impairment. In spite of significant mass effect on CT scan, the patients remained alert, ambulatory and independent. We believe that some cases of cerebral necrosis following radiotherapy for extra-cranial neoplasms present in a more benign fashion than has been portrayed in the literature, and in the absence of clinical evidence of raised intracranial pressure, surgical intervention is unnecessary. The importance of careful fractionation of an optimum radiation dose as a preventive measure is emphasised.