Carcinogenesis at colonic anastomotic sites

For three months 65 male Sprague-Dawley rats received subcutaneous 1,2-dimethylhydrazine (DMH) weekly. Of the 65 animals, 45 were subjected to resection of the transverse colon, which subsequently was stitched to the abdominal wall. The remaining 20 animals were shamoperated controls. Fifty-four per cent of the tumors occurred either at the anastomotic site in the functioning colon (31 per cent) or at the anastomotic site of the isolated and defunctionalized colonic loop (23 per cent). On the other hand, only 10 per cent of the tumors occurred in the transverse colon of sham-operated controls. The difference was significant (P<0.001). This study was supported by grants from the Cancer Society, Stockholm, and the Karolinska Institute.     

Selective regulation of nerve growth factor expression in developing cutaneous tissue by early sensory innervation

Background

In the developing vertebrate peripheral nervous system, the survival of sympathetic neurons and the majority of sensory neurons depends on a supply of nerve growth factor (NGF) from tissues they innervate. Although neurotrophic theory presupposes, and the available evidence suggests, that the level of NGF expression is completely independent of innervation, the possibility that innervation may regulate the timing or level of NGF expression has not been rigorously investigated in a sufficiently well-characterized developing system.

Results

To address this important question, we studied the influence of innervation on the regulation of NGF mRNA expression in the embryonic mouse maxillary process in vitro and in vivo. The maxillary process receives its innervation from predominantly NGF-dependent sensory neurons of the trigeminal ganglion and is the most densely innervated cutaneous territory with the highest levels of NGF in the embryo. When early, uninnervated maxillary processes were cultured alone, the level of NGF mRNA rose more slowly than in maxillary processes cultured with attached trigeminal ganglia. In contrast to the positive influence of early innervation on NGF mRNA expression, the levels of brain-derived neurotrophic factor (BDNF) mRNA and neurotrophin-3 (NT3) mRNA rose to the same extent in early maxillary processes grown with and without trigeminal ganglia. The level of NGF mRNA, but not BDNF mRNA or NT3 mRNA, was also significantly lower in the maxillary processes of erbB3 ^-/- mice, which have substantially fewer trigeminal neurons than wild-type mice.

Conclusions

This selective effect of initial innervation on target field NGF mRNA expression provokes a re-evaluation of a key assertion of neurotrophic theory that the level of NGF expression is independent of innervation.     

Socio-economic impact of endovenous thermal ablation techniques

Varicose veins are common and cause extensive morbidity; however, the value of treatment is under-appreciated. Many procedures allow the treatment of varicose veins with minimal cost and extensive literature supporting differing minimally invasive approaches. In this article, we investigate the current literature regarding treatment options, clinical outcome and the cost-benefit economics associated with varicose vein treatment. The practice of defining clinical outcome with quality of life (QOL) assessment is explained to provide valid concepts of treatment success beyond occlusion rates.     

Influence of cholesteryl ester transfer protein, peroxisome proliferator-activated receptor α, apolipoprotein E, and apolipoprotein A-I polymorphisms on high-density lipoprotein cholesterol, apolipoprotein A-I, lipoprotein A-I, and lipoprotein A-I:A-II concentrations: the Prospective Epidemiological Study of Myocardial Infarction study

The plasma level of high-density lipoprotein cholesterol (HDL-C) is known to be inversely associated with cardiovascular risk. However, besides lifestyle, gene polymorphism may influence the HDL-C concentration. The aim of this study was to investigate the possibility of interactions between CETP, PPARA, APOE, and APOAI polymorphisms and HDL-C, apolipoprotein (apo) A-I, lipoprotein (Lp) A-I, and Lp A-I:A-II in a sample selected from the Prospective Epidemiological Study of Myocardial Infarction (PRIME) study population who remained free of cardiovascular events over 5 years of follow-up. Healthy individuals (857) were randomly selected for genotyping the PRIME study subjects. The population was selected so as to provide 25% of subjects in the lowest tertile of HDL-C (≤28 mg/dL) in the whole PRIME study sample, 25% of subjects in the highest tertile of HDL-C (≥73 mg/dL), and 50% of subjects in the medium tertile of HDL-C (28-73 mg/dL). Genotyping was performed by using a polymerase chain reaction system with predeveloped TaqMan allelic discrimination assay. The CETP A373P rare allele c was less frequent in the group of subjects with high HDL-C, apo A-I, Lp A-I, and Lp A-I:A-II concentrations. Apolipoprotein A-I and Lp A-I were also found to be higher in the presence of the ?2 allele coding for APOE. The effect of the CETP A373P rare allele c on HDL-C was independent of all tested parameters except triglycerides. The respective effect of these polymorphisms and triglycerides on cardiovascular risk should be evaluated prospectively.     

Effects of prior administration of steroids upon recovery from lethal sepsis

The effects upon survival of large doses of steroid administered to dogs prior to challenging them with lethal sepsis was evaluated in this study. Dogs were given 30 milligrams per kilogram of body weight per day of methylprednisolone sodium succinate for one, two or eight days and then were infused with 9.72 +/- 0.35 X 10(9) Escherichia coli per kilogram of body weight. All dogs in group 1 (n equals six) not given steroid died within 25 hours. Of the dogs in group 2 (n equals 12) given one or two doses of steroid previously, 42 per cent permanently survived (more than seven days). All dogs in group 3 (n equals five) given eight daily doses of steroid prior to infusion of Escherichia coli died within 17 hours. Dogs in group 4 (n equals six) were given eight daily doses of steroid prior to infusion of Escherichia coli and treated on the day of infusion of Escherichia coli with a regimen of methylprednisolone and gentamicin sulfate which results in a 100 per cent survival rate when given to dogs that have not received prior treatment with steroid. Thirty-three per cent of the dogs in group 4 permanently survived. One or two daily large doses of steroid did not detrimentally affect survival of the dogs. Eight days of steroid administration suppressed endogenous cortisol production. When the dogs were treated with six hours of steroid-antibiotic therapy, survival benefits were limited.     

Melanoma uptake of (99m)Tc complexes containing the N-(2-diethylaminoethyl)benzamide structural element

On the basis of the avid uptake of radioiodinated benzamides by melanoma cells, (99m)Tc complexes containing the structural elements of N-(dialkylaminoalkyl)benzamide pharmacophores have been synthesized and evaluated in vitro and in vivo for melanoma uptake. One of the complexes Tc-12 containing the ligand 4-(S-benzoyl-2-thioacetyl-glycyl-glycylamido)-N-(2-diethylaminoethyl)benzamide (11) displayed the highest melanoma uptake. The 1-h melanoma uptake values and the corresponding blood counts indicate an interdependence of tumor uptake and bioavailability of the (99m)Tc complexes.