Chemoprevention of spontaneous tumorigenesis in nullizygous p53- deficient mice by dehydroepiandrosterone and its analog 16alpha-fluoro- 5-androsten-17-one

Transgenic mice with both alleles of the p53 tumor suppressor gene product 'knocked out' by gene targeting are susceptible to early development of tumors, chiefly lymphomas and sarcomas. Compared with the control group, administration of dehydroepiandrosterone (DHEA) at 0.3% of the diet to male p53-deficient mice extended their lifespan by delaying death due to neoplasms (from 105 to 166 days on study, P = 0.002), primarily by suppressing lymphoblastic lymphoma (from 45 to 6% of neoplastic deaths, P = 0.010). Treatment with a synthetic DHEA analog, 16alpha-fluoro-5-androsten-17-one (compound 8354), at 0.15% of the diet also increased lifespan, to 140 days for mice that developed tumors (P = 0.037). The effects of these steroids on lifespan and tumor development did not appear to be strongly related to inhibition of food consumption and weight gain, in that a group pair-fed with control diet to the reduced food consumption of the DHEA-treated group developed and died of the same types of neoplasms at the same rate as the controls fed ad libitum. The chemopreventive effect of these steroids has been proposed to be due to suppression of DNA synthesis by inhibition of glucose 6-phosphate dehydrogenase, the rate-limiting enzyme of the pentose phosphate pathway. Although DHEA and its analog are strong non- competitive inhibitors of this enzyme in vitro, treatment with DHEA did not deplete cellular nucleotide pools in the liver, as would have been predicted. The chemopreventive effect of DHEA in this model may be due to steroid-induced thymic atrophy and suppression of T cell lymphoma, permitting these mice to survive long enough to develop tumors with longer latency.      

Failure of ablation of a mediastinal parathyroid adenoma by repeated contrast staining

In a patient with primary hyperparathyroidism an attempt was made to ablate a middle mediastinal parathyroid gland by forceful staining with radiographic contrast material. The gland was stained on two separate occasions, two weeks apart. Both times the serum calcium level temporarily fell to the normal range but reverted to abnormal levels. The patient ultimately required surgery for correction of hypercalcemia. The mechanism of staining and possible reasons for failure as well as potential complications are discussed.     

Gallium-67 lung uptake: conjugate-view technique

A conjugate-view technique is derived for calculation of absolute gallium-67 (Ga-67) uptake from scintillation-camera images. The technique combines counts of posterior and anterior images of the lung with an attenuation correction obtained from cobalt-57 (Co-57) transmission imaging. The formulation is such that the effects of Compton scatter build-up are accounted for. Studies utilizing a canine model indicated that, normally, more activity is located in the chest wall than in the lungs. The quantitative technique must therefore accurately account for a variety of Ga-67 distributions, including that in the chest wall. Calculations were performed using a three-component model comparing results obtained with the conjugate-view approach to the actual uptake. These calculations suggest that an assumption of uniform activity distribution allows an accuracy of approximately +/- 10% over a broad range of body-part thicknesses and uptake by the lungs. It was concluded that the conjugate-view technique is necessarily approximate but can provide clinically useful results.     

The relation beween he bactericidal activities and certain physico-chemical properties of some fluorophenols

The antibacterial activities, as demonstrated by the Rideal-Walker coefficients and viable counts, of mono-, 2,4,5– tri-, 2,3,5,6- tetra- and pentafluorophenol increase with the number of substituent fluorine atoms. The thermodynamic activities (Ferguson values) range from 0·083 to 0·022, and indicate a non-specific physical mode of action. Linear correlations occur between the equitoxic concentrations of the compounds to Escherichia coli (99·9% mortality after 50 min contact) and their molecular weights, number of fluorine substituents and water solubilities. A similar relation exists between the molar concentrations at the Rideal-Walker end points and the oleyl alcohol-water partition coefficients; no correlation occurs between toxicity and the cyclohexane-water partition coefficients. The surface tensions of equitoxic solutions vary between 57·5 and 63·2 mNm^?1 (dynes/cm).     

Anti-human leukocyte antigen antibodies are associated with restenosis after percutaneous coronary intervention for cardiac allograft vasculopathy

BACKGROUND: Percutaneous coronary intervention (PCI) to palliate cardiac allograft vasculopathy (CAV) has been associated with high restenosis rates, possibly related to increased inflammation associated with this disease. Whether markers of immunologic rejection are associated with restenosis in this population is unknown. The goal of the study was to determine the predictors of restenosis after PCI for CAV. METHODS: Records were reviewed retrospectively from a single, high-volume cardiac transplant center. Clinical, angiographic, and immunologic data were collected on all patients postorthotopic heart transplantation (OHT) that had subsequent PCI. Restenosis was defined as greater than 50% stenosis at the previous intervention site. RESULTS: PCI was successfully performed on 62 de novo lesions in 40 patients an average of 6.8+/-3.9 years after OHT. Angiographic follow-up data was available for 79%, with an average follow-up of 1.54+/-1.22 years. The 1-year restenosis rate was 49% (64% for balloon percutaneous transluminal coronary angioplasty and 33% for coronary stenting [P=0.09 for difference]). The frequency of immunoglobulin (Ig)G antibody to major histocompatibility complex (MHC) class I antigen was highly associated with risk of restenosis (hazard ratio [HR] 11.33, P=0.01). Greater stenosis severity and smaller target vessel diameter were also predictors of restenosis as in the nontransplant population. CONCLUSIONS: The findings suggest that in patients postPCI for CAV, humoral allo-immunity may contribute to restenosis and that IgG antibodies to MHC class I antigen may help predict the risk of restenosis after PCI in this population.     

Platelet Functions in Cardiopulmonary Bypass Surgery

Background

Haemorrhage after Cardio Pulmonary Bypass (CPB) Surgery is a well recognised complication that leads to significant morbidity and mortality. The incidence varies between 5-25% depending upon the clinical situation. Several factors are implicated as causative but none have been precisely proved.

Methods

Our study was an attempt to evaluate the haemostatic defect with particular reference to platelet function abnormalities during cardio pulmonary bypass surgery, in order to reduce the morbidity and mortality associated with post CPB haemorrhage. Flow cytometric evaluation of different platelet glycoproteins like GPIb/IX, GPIIb/IIIa and GMP-140 was done.

Results

The marker expression showed deregulation during surgery which returned to base after bypass was terminated. In contrast, the cases with bleeding showed significant variation. P-Selectin (GMP 140) expression decreased progressively till 3^rd post-operative day showing lack of activation of platelets in cases of severe bleeding.

Conclusion

Longer duration of CPB initiates plasmin generation through heparin, which raises the PAI-1-tPA complex and thereby down regulating the functions of platelets. This suggests a link between duration of CPB, bleeding, platelet dysfunction and fibrinolysis. Hence serial estimations of the levels of GMP-140 and tPA can predict severe bleeding.Key Words: CardioPulmonary Bypass, Platelet dysfunction, flowcytometry, platelet glycoproteins, haemorrhage