Theoretical QSAR study on carcinogenic potency of N-nitrosamines

A mechanistic QSAR study on N-nitrosamines (NA) was performed with the aid of the semiempirical MINDO/3 method. Both the chemical reactivity and the transport in biological medium were taken into account. The parent NA molecules and their first reaction intermediates in the metabolic activation pathway were examined for possible determinants of the relative carcinogenic potency. The correlations found support the previous suggestions concerning the metabolic C alpha radical hydroxylation of NA. The role of transport properties in the early stage of NA biotransformation was also demonstrated.     

Effect of diffusion chamber pore size on differentiation and proliferation of periosteal cells. An experimental study

The influence of the pore size of Nucleopore diffusion-chamber filters on the rate of proliferation and differentiation of periosteal cells in muscle was studied in 44 growing rabbits. Periosteal grafts were placed in chambers (16-19 in each experimental group) sealed with filters with a pore size of 0.4, 0.6, 0.8, 1.0, or 2.0 micron. Each chamber was implanted into the paraspinal muscle of the rabbit, where it remained for 16 weeks. The osteochondrogenic activity of the graft grew linearly when the pore size increased from 0.4 to 1.0 micron. In the chambers with a pore size of 2.0 micron, both bone and cartilage were found in only one chamber. Bone and cartilage were not found outside any of the chambers. The present results showed that the pore size of the filters significantly affected the ability of the periosteal graft to form bone and cartilage.     

The effects of bulk versus particulate polymethylmethacrylate on bone

Twenty-one mature New Zealand white female rabbits were allocated into three groups of seven rabbits. Group I received a bolus of doughy Simplex polymethylmethacrylate (PMMA) cement injected into the proximal tibia through a drill hole. Group II received a preformed, cooled, bulk PMMA pellet. Group III had particulate PMMA powder implanted. The operated, but nonimplanted, left tibiae served as controls. Animals were killed after four months. Histologically, both Group I and Group II demonstrated a thin, fibrous tissue membrane at the implant interface. Particulate PMMA (Group III) stimulated a much thicker, florid, foreign body reaction composed of histiocytes and giant cells. The foreign body response to particulate acrylic cement was similar to that seen in failed cemented joint replacement arthroplasty in humans.     

Lumbar facet joint tropism does not accelerate degeneration of the facet joints.

PURPOSETo study the relationship of lumbar facet joint tropism to degeneration of the cartilage and subcortical bone in the facet joints and the effect of tropism in intervertebral disk degeneration.METHODSThe orientation of 104 cadaveric lumbar facet joints with respect to sagittal plane was measured on CT scans, and the joints were classified as having no tropism, mild tropism, or severe tropism. On MR images, the severity of cartilage degeneration and bony sclerosis was measured. The correlation between tropism and degeneration was calculated, as was the relationship among age, spinal level, and degeneration.RESULTSWe identified four spinal levels with severe tropism, six with moderate tropism, and 94 without tropism. Cartilage degeneration was not significantly more severe in the joints with tropism than in the joints without. Sclerosis was slightly greater in the joints with tropism than in the joints without it. Sclerosis and cartilage degeneration were significantly related to age and spinal level.CONCLUSIONAge, spinal level, and overall facet joint angle are more important factors in facet joint degeneration than is tropism.     

High-resolution loading tests in the study of genetic heterogeneity in gangliosidosis fibroblasts

Summary GM₁- and GM₂-gangliosides were isolated from brain and radio-labelled. The labelled moieties were localized by hydrolysis with lysosomal enzymes, followed by thin-layer chromatography of the products. High-resolution loading tests with labelled gangliosides were developed and found to differentiate infantile and juvenile forms of GM₁- and GM₂-gangliosidoses as well as the identification of B, O and AB types of GM₂-gangliosidosis.     

Effects of hyperthermia on blood flow and cis-diamminedichloroplatinum(II) pharmacokinetics in murine mammary adenocarcinomas.

The effect of localized hyperthermia on blood flow and cis-diamminedichloroplatinum(II) (CDDP) pharmacokinetics in 7,12-dimethylbenz[a]anthracene-induced mammary adenocarcinomas was studied. Blood flow was determined in rat tumors and normal tissue immediately and 1, 2, and 3 h after local hyperthermia treatment (43 degrees C, 1 h) as well as in unheated tumors of rats. The rate of blood flow in the tumor was increased 1.9 times at the end of treatment relative to control values and returned to the control values by 3 h after hyperthermia. Similarly, the rate of blood flow in the peripheral skin around the tumor immediately after hyperthermia was 2.2 times greater than that of unheated skin and returned to near normal values by 3 h after heating. Tumor-bearing rats received CDDP 1 h before, at the beginning of, at the end of, and 1 h after hyperthermia administration. The CDDP plasma concentration versus time profiles for rats did not vary statistically between treatment groups. Two h after CDDP administration, the mean tumor CDDP concentration of the rats which received drug at the beginning of hyperthermia was statistically greater (P less than 0.05) than tumor CDDP concentrations in rats which received drug at the end of heat treatment. The latter group was given CDDP when tumor blood flow was the greatest; however, mean tumor drug concentration was lowest of all the groups. The mean drug concentration in tumor tissues of rats which received drug 1 h after hyperthermia was comparable to rats which received drug at the beginning of hyperthermia. This suggests that drug delivery or uptake in tumors may be altered when local hyperthermia is administered concurrently or sequentially.     

Does the Extent of Surgery Make a Difference in High Grade Malignant Astrocytoma?

This paper examines the effect of patient age, tumour grade and extent of surgery on the outcome of treatment of 278 patients with high grade malignant gliomas referred to the Queensland Radium Institute between 1980 and 1987. The aim was to determine whether the extent of surgical resection alters survival rates. The extent of surgery had no effect on survival except for those patients with grade 3 tumours in whom a total excision was possible. Those in whom only a biopsy was done did not have a worse prognosis. Grading was found to be of importance, as patients with grade 3 tumours had a better survival than those with grade 4 tumours. In grade 4 tumours, those under 30 years of age had a better survival than those over 30 years, whereas with grade 3 tumours there was a gradation of age effect (under 40 years best, then 40–49 years, and those 50 years and over doing worst).