Lack of high-dose radiation mediated prostate cancer promotion and low-dose radiation adaptive response in the TRAMP mouse model.

Cancer of the prostate is a highly prevalent disease with a heterogeneous aetiology and prognosis. Current understanding of the biological mechanisms underlying the responses of prostate tissue to ionizing radiation exposure, including cancer induction, is surprisingly limited for both high- and low-dose exposures. As population exposure to radiation increases, largely through medical imaging, a better understanding of the response of the prostate to radiation exposure is required. Low-dose radiation-induced adaptive responses for increased cancer latency and decreased cancer frequency have been demonstrated in mouse models, largely for hematological cancers. This study examines the effects of high- and low-dose whole-body radiation exposure on prostate cancer development using an autochthonous mouse model of prostate cancer: TRansgenic Adenocarcinoma of the Mouse Prostate (TRAMP). TRAMP mice were exposed to single acute high (2 Gy), low (50 mGy) and repeated low (5 × 50 mGy) doses of X rays to evaluate both the potential prostate cancer promoting effects of high-dose radiation and low-dose adaptive response phenomena in this prostate cancer model. Prostate weights and histopathology were examined to evaluate gross changes in cancer development and, in mice exposed to a single 2 Gy dose, time to palpable tumor was examined. Proliferation (Ki-67), apoptosis, DNA damage (γ-H2AX) and transgene expression (large T-antigen) were examined within TRAMP prostate sections. Neither high- nor low-dose radiation-induced effects on prostate cancer progression were observed for any of the endpoints studied. Lack of observable effects of high- or low-dose radiation exposure suggests that modulation of tumorigenesis in the TRAMP model is largely resistant to such exposures. However, further study is required to better assess the effects of radiation exposure using alternative prostate cancer models that incorporate normal prostate and in those that are not driven by SV40 large T antigen.

False-positive TUNEL staining observed in SV40 based transgenic murine prostate cancer models.

The TRAMP (Transgenic Adenocarcinoma of the Mouse Prostate) and LADY (Probasin-large T antigen transgenic mouse) mice are widely used autochthonous models of prostate cancer. Both models utilise probasin promoters to direct androgen-regulated expression of oncogenic SV40 specifically to epithelial cells of the mouse prostate. The oncogenic processes and phenotypes which result mimic many features of human prostate cancer, making these transgenic mouse models useful experimental systems. The terminal deoxynucleotidyl transferase (Tdt)-mediated dUTP in situ nick end labelling (TUNEL) assay is a commonly used method for the detection of cells undergoing apoptosis. In this study, we demonstrate false-positive TUNEL staining in frozen prostate tissue from TRAMP and LADY mice, which was not observed in non-transgenic control animals and is not due to non-specific binding of labelled-dUTP substrate. The false-positive signal co-localised with large SV40 T-antigen expression. False-positive signal was apparent using multiple commercial TUNEL kits with different detection systems. These results caution against the use of the TUNEL assay for detection of apoptosis in frozen prostate tissue of large T-antigen based autochthonous transgenic models of prostate cancer.

Gorlin syndrome associated with midline nasal dermoid cyst.

Gorlin syndrome is an autosomal dominant multisystem disorder characterised by multiple basal cell naevi, cysts of the jaw, pits of the palms and soles, skeletal anomalies, and various other defects. Patients with Gorlin syndrome have a predisposition to basal cell carcinomas and other neoplasms. This is the first report to describe the coexistence of Gorlin syndrome and a nasal dermoid cyst. A 4 year old girl was diagnosed with medulloblastoma and treated with surgery and radiation therapy. A genetic evaluation was sought because of the brain tumour, multiple small naevi localised mostly on the upper torso, and rib abnormalities. Biopsies of several naevi showed naevoid basal cell carcinoma. Past medical history was significant for a midline nasal punctum noted at birth. The significance of this finding was unrecognised until the dermoid cyst enlarged, just before the diagnosis of her brain tumour. A common tissue of origin exists between basal cell naevi, cysts of the jaw, and dermoid cysts. We propose that the association of these two rare conditions in one patient is not a chance occurrence.

Utility of an automatic instrument for blood pressure measurement in children. The Bogalusa Heart Study.

The Dinamap 845XT automatic blood pressure monitor, Dinamap 8100 (an update model), and two mercury sphygmomanometers were compared in 417 school-aged children examined in the spring of 1992 as part of the Bogalusa Heart Study. This study was conducted in the nearby community of Franklinton, Louisiana, to verify data obtained as part of a cross-sectional survey (1987 to 1988) of school-aged children in Bogalusa. Systolic blood pressure levels were on the average 3 mm Hg higher on the Dinamap instruments than on the sphygmomanometers. Mean levels of diastolic blood pressure using either Dinamap instrument were slightly higher until eight years of age and then were considerably lower than mercury sphygmomanometer fourth phase readings. Diastolic blood pressure levels on the Dinamap 8100 were 4 mm Hg lower than on the Dinamap 845XT. Height was identified as the predominant predictor variable of differences in diastolic blood pressure between the mercury sphygmomanometer and either Dinamap instrument. A 10% random sample of children was reexamined each screening day in the cross-sectional survey to estimate measurement errors. The diastolic readings of the Dinamap 845XT had a lower intraclass correlation (0.68) compared to the mercury sphygmomanometers (0.83 fourth phase and 0.76 fifth phase). The Dinamap offers the ease of measuring systolic blood pressure although the diastolic blood pressure appears to be biased and especially low, particularly on the new 8100 model.

Splenic rupture resulting from acute pancreatitis after cardiac surgery with intra-aortic balloon pumping: case report.

A very unusual cause of splenic rupture is described in a 73-year-old man with severe coronary artery disease. A transthoracic intra-aortic balloon pump (IABP) was inserted during coronary artery bypass grafting and was used for 3 days. However, his hypotension continued, and ischemic changes in his hand were thought to be due to the use of the pump. He died 7 days later of cardiac arrest. Autopsy revealed multiorgan failure associated with a preoperative myocardial infarct. Numerous systemic arterial atheroemboli, likely resulting from IABP-related aortic trauma and hypotension, had given rise to severe acute pancreatitis. The necrotizing process within the pancreatic tail had extended to the splenic hilum, eroding its capsule and causing splenic rupture and hemoperitoneum.

Anatomy and fine structure of neurons in the deutocerebral projection pathway of the crayfish olfactory system.

Golgi impregnation and neurobiotin injection were used to examine details of the neural pathways in the olfactory system of the freshwater crayfish, Procambarus clarkii. Deutocerebral projection neurons (globuli cells) were directly injected with neurobiotin. These neurons have dendritic arborizations in the ipsilateral olfactory and accessory lobes, and they project axons to the lateral protocerebrum, where they terminate in microglomeruli of the hemi-ellipsoid body. The axons of the deutocerebral projection neurons are readily impregnated by Golgi procedures, and they terminate as an expanded membranous knot about 5 microns in diameter. Electron microscopy on Golgi-stained terminals has revealed that each knot makes several hundred synapses with small spine-like or shaft-like processes of postsynaptic neurons. Injection of neurobiotin into local interneurons of the hemi-ellipsoid body and subsequent examination of stained preparations with the electron microscope reveals that these cells are a major postsynaptic target of the deutocerebral projection neurons. Furthermore, the local interneurons make extensive efferent synaptic connections with unidentified neurons in the terminal medulla.

Needle-sharing among intravenous drug users in New Orleans.

We studied needle sharing among intravenous drug users in New Orleans, where needles are not controlled by prescription. Three hundred and eighty self-identified intravenous drug users were interviewed regarding needle-sharing practices, frequency of drug use, and drug(s) of choice. Overall, 65.8% admitted they regularly used needles which had been used by others. No significant differences in needle sharing were found by sex, race, frequency of injection, or drug of choice. A survey of pharmacies found that 85.5% have self-imposed restrictions on the sale of needles and syringes. Legal availability of injection equipment may not be equivalent to actual availability to the consumer.

Polyuria among patients with psychosis.

Using the criterion of early morning urinary specific gravity (SPGR) of 1.008 or less to define the presence of polyuria, we identified 26 of 72 male (36 percent) and 14 of 31 female (45 percent) institutionalized chronically psychotic patients as polyuric during a comprehensive survey of one of the chronic care units at a State mental hospital. Factors including diagnosis, sex, age, weight, and serum sodium did not distinguish the polyuric from the nonpolyuric patients. For men, administration of lithium was associated with polyuria. Urinary creatinine concentration (UCR) correlated well with SPGR, and UCR may provide an alternate index to separate polyuric from nonpolyuric patients. The clinical implications of our findings are discussed.