Comparison of enhancement of GGTase-positive foci and induction of ornithine decarboxylase in rat liver by barbiturates

The induction of ornithine decarboxylase (ODC) by barbituratesand the ability of barbiturates to enhance neoplastic progressionof chemically initiated cancer was examined in rat liver. Allseven barbiturates induced ODC with barbital (7.7 fold increase)and phenobarbital (5.7 fold increase) demonstrating the mostpotent activity. Maximum induction of ODC by phenobarbital wasobtained in 18 h. Barbital (500–5000 p.p.m.) and phenobarbital(500 p.p.m.) administered in the drinking water enhanced theappearance of diethylnitrosamine (DENA)-initiated -glutamyltranspeptidase(GGTase)-positive foci. Amobarbital, hexabarbital and pentabarbitaldid not enhance the appearance of GGTase-positive foci. In theabsence of previous initiation by DENA, the enhancing regimenof the barbiturates did not cause the appearance of GGTase-positivefoci. Barbiturates induced ODC activity in rat liver and enhancedthe incidence of DENA initiated GGTase-positive foci.     

Paraplegia episodes revealing tuberculous myelitis

A 38 year-old woman, without previous medical history, presented, since 1993, several paraplegic fits carrying herself progressively through to a severe paraplegia. Diagnoses successively proposed were spinal cord compressions by slipped discs, spinal cord infarct and multiple sclerosis. In November 1998, the patient presented back pain and fever. Spinal cord magnetic resonance imaging (MRI) revealed a mildly enlarged dorsal cord with signal abnormalities. The lesions were isointense on T1-weighted images, hyperintense on T2-weighted images and showed a ringlike contrast enhancement. A lumbar puncture showed a trouble cerebrospinal fluid (CSF) with leucocytes 600/mm(3) (85 p.100 polynuclear), protein 6.7 g/l, glucose 0.26 g/l, chloride 109 mmol/l. The patient was first treated with parenteral unspecific antibiotherapy. Microbiological studies of blood and CSF were negative. CSF examination with polymerase chain reaction (PCR) was positive for Mycobacterium tuberculosis. Clinical (pain and fever) symptoms and CSF abnormalities decreased after antituberculous treatment. However, paraparesis remain severe. Spinal tuberculous localizations often lead to diagnostic and therapeutic errors. Improvement of spinal cord MRI sequences and using of PCR technics in CSF would contribute to reduce these difficulties.     

Paediatric renal transplantation in Northern Ireland (1984-1998)

Over the last 20 years a comprehensive paediatric nephrology service has been developed in Northern Ireland, based in the academic medical unit at the Royal Belfast Hospital for Sick Children (RBHSC). In the 15 years 1984-1998 a total of 77 renal transplants have taken place in patients aged 18 years and under. Initially transplants were only considered in children over five years of age but in the past eight years children as young as two years have successfully received kidneys. Aggressive nutritional support combined with peritoneal dialysis has enabled survival to a size when transplantation is feasible. The 5 year graft survival was 64%, with two children dying following transplantation. The complexity of managing this age group is reflected by the fact that a total of 10 transplants (13%) failed in the first 30 days. These figures compare favourably with statistics reported by similar paediatric centres from across the United Kingdom and Republic of Ireland, and with local results in adult patients. This demonstrates that a successful end stage renal replacement programme for children is achievable in a relatively small population, which is geographically isolated.     

Underprediction of visibly complex chromosome aberrations by a recombinational-repair ('one-hit') model

PURPOSE: Published low-LET FISH data were used to test two models of chromosome aberration production based on breakage-and-reunion or recombinational repair. MATERIALS AND METHODS: Randomness of DNA double strand break induction and misrejoining is analyzed comprehensively and adopted as a working hypothesis. Proximity effects are approximated by using interaction sites. Model results are calculated using CAS (chromosome aberration simulator) Monte Carlo computer software with two adjustable parameters. CAS can emulate the specifics of any experimental painting protocol, allowing very detailed tests of the models. RESULTS: To reasonable approximation, breakage-and-reunion model predictions are consistent with low-LET FISH results, including two large, elaborate, one-paint data sets. An explicitly specified version of the recombinational-repair model severely underpredicts the frequency of the visibly complex aberration patterns most commonly observed with one-paint FISH, and is inconsistent with some observed multi-paint patterns. When high-dose effects (distortion and saturation) are taken into account quantitatively, a dose-response relation for apparently simple interchanges slightly favours the breakage-and-reunion model over the recombinational-repair model, despite being approximately linear over the dose range 2-6 Gy. CONCLUSIONS: The random breakage-and-reunion model gives comprehensive baseline predictions that are sufficiently accurate for the organization of experimental results. The data speak against complex aberrations being formed by the random recombinational repair pathway discussed here.     

Medical management of metastatic skeletal disease

The medical management of metastatic disease generally includes chemotherapy, hormonal therapy, and metabolic pharmacologic manipulations with medications, such as bisphosphonates as well as nonoperative physical measures, such as orthoses and ambulatory or mobility aids. This comprehensive complex care is best coordinated with the medical oncologist. If well planned and coordinated, such care can improve the life of the cancer patient greatly.     

Volume reduction in the caudate nucleus following stereotactic placement of lesions in the anterior cingulate cortex in humans: a morphometric magnetic resonance imaging study

OBJECT: The goal of this study was to test hypotheses regarding changes in volume in subcortical structures following anterior cingulotomy. METHODS: Morphometric magnetic resonance (MR) imaging methods were used to assess volume reductions in subcortical regions following anterior cingulate lesioning in nine patients. Magnetic resonance imaging data obtained before and 9 +/- 6 months following anterior cingulotomy were subjected to segmentation and subcortical parcellation. Significant volume reductions were predicted and found bilaterally within the caudate nucleus, but not in the amygdala, thalamus, lenticular nuclei, or hippocampus. Subcortical parcellation revealed that the volume reduction in the caudate nucleus was principally referrable to the body, rather than the head. Furthermore, the magnitude of volume reduction in the caudate body was significantly correlated with total lesion volume. CONCLUSIONS: Taken together, these findings implicate significant connectivity between a region of anterior cingulate cortex (ACC) lesioned during cingulotomy and the caudate body. This unique data set complements published findings in nonhuman primates, and advances our knowledge regarding patterns of cortical-subcortical connectivity involving the ACC in humans. Moreover, these findings indicate changes distant from the site of anterior cingulotomy lesions that may play a role in the clinical response to this neurosurgical procedure.     

Vascular modulation through exercise improves chemotherapy efficacy in Ewing sarcoma

Recent studies in mouse models of cancer have shown that exercise improves tumor vascular function, thereby improving chemotherapy delivery and efficacy. However, the mechanisms underlying this improvement remain unclear and the effect of exercise on Ewing sarcoma (ES), a pediatric bone and soft tissue cancer, is unknown. The effect of exercise on tumor vascular hyperpermeability, which inversely correlates with drug delivery to the tumor, has also not been evaluated. We hypothesized that exercise improves chemotherapy efficacy by enhancing its delivery through improving tumor vascular permeability. We treated ES‐bearing mice with doxorubicin with or without moderate treadmill exercise. Exercise did not significantly alter ES tumor vessel morphology. However, compared to control mice, tumors of exercised mice had significantly reduced hyperpermeability, significantly decreased hypoxia, and higher doxorubicin penetration. Compared to doxorubicin alone, doxorubicin plus exercise inhibited tumor growth more efficiently. We evaluated endothelial cell sphingosine‐1‐phosphate receptors 1 and 2 (S1PR1 and S1PR2) as potential mediators of the improved vascular permeability and increased function afforded by exercise. Relative to tumors from control mice, vessels in tumors from exercised mice had increased S1PR1 and decreased S1PR2 expression. Our results support a model in which exercise remodels ES vasculature to reduce vessel hyperpermeability, potentially via modulation of S1PR1 and S1PR2, thereby improving doxorubicin delivery and inhibiting tumor growth more than doxorubicin alone does. Our data suggest moderate aerobic exercise should be tested in clinical trials as a potentially useful adjuvant to standard chemotherapy for patients with ES.