Management of skeletal metastases

Bone is a frequent site of tumour metastasis and is the third most common site of metastatic carcinoma. With advances in the use of immunotherapy, hormonal manipulation, chemotherapy and radiation for the palliation of patients with metastatic bone disease, significant improvements in survival, wellbeing and overall quality of life have been achieved.     

Formation of pannus on prosthetic valves in a child with pseudoxanthoma elasticum

A child with pseudoxanthoma elasticum had mitral valvar prolapse with severe regurgitation necessitating replacement with a prosthetic valve. Extensive formation of pannus caused obstruction of two mechanical valves, one after twenty months and the second after three years. Histology of the pannus was similar to the endocardial lesions that are considered unique to pseudoxanthoma elasticum.     

DNA lesion complexity and induction of apoptosis by ionizing radiation

PURPOSE: To determine whether murine lymphoid cell lines can discriminate between high- and low-LET (linear energy transfer) radiation-induced DNA lesions. MATERIALS AND METHODS: Sensitivity to killing by DNA-incorporated 3H and 125I decays, accumulated during storage in the gas phase of a liquid nitrogen tank, was determined by clonogenic survival assay. RESULTS: Induction of a lethal event in the STRij-4-2.2, WEHI-22.1, and L5178Y-R cell lines required approximately 30 times more 3H than 125I decays. Hence, the same ratio of 3H to 125I decays was found irrespective of whether the cell lines contained mutant or wild-type p53 and irrespective of whether they underwent rapid interphase or mitosis-related apoptosis after irradiation. The 18-81 cell line differed in showing a ratio of around 21 and it is argued that this may be a consequence of v-ABL over-expression. The assumption that DNA-incorporated 3H and 125I decays are low- and high-LET-like events respectively was confirmed by the similar sensitivity of L5178Y-R and -S cells to killing by 125I decays in contrast with their difference in sensitivity to 3H decays. CONCLUSIONS: The difference in lethal effectiveness between DNA-incorporated 3H and 125I decays can be explained by the hypothesis that simple DSB (double-strand breaks) are non-lethal and that cell killing is attributable to complex DSB. The low-LET radiation-specific sensitization of L5178Y-S cells may reflect defective repair of a DNA lesion class (presumably simple DSB) that is differentially induced by high- and low-LET radiation and is non-lethal to cells with normal repair capacity.     

Model for the initiation of ionizing radiation-induced apoptosis in lymphoid cells by complex DNA double-strand breaks

PURPOSE: To present a model for the molecular events that lead to the induction of apoptosis in irradiated lymphoid cells based on the assumption that the process is triggered by complex DNA double-strand breaks (DSB). OUTLINE OF THE MODEL: * Cellular DNA repair mechanisms have difficulty rejoining complex DSB because of the nature of the end groups on such breaks. * Association between p53 and DNA topoisomerase I (topo I) can occur at complex DSB in open regions of the genome and the enzymic activity of such associations is not suppressed by polyADP-ribosylation. * Binding of p53 and topo I at a complex DSB results in the transient trapping of a DNA-topo I cleavage complex. * Transiently trapped DNA-topo I cleavage complexes at complex DSB are reversed following association with topo I bound elsewhere in the genome, thus initiating a misrejoining event. * Topo I-mediated DNA misrejoining creates a structure that activates p53. Initiation of rapid interphase apoptosis requires that the inducing signal from activated p53 exceeds a threshold level. * Initiation of rapid interphase apoptosis is regulated by poly(ADP-ribose) polymerase.     

Bacteria-eradicating therapy for ocular adnexal MALT lymphoma: questions for an open international prospective trial.

We read with great interest the article by Grünberger etal. on the ‘blind’ administration of doxycyclinein a retrospective series of 11 patients with ocular adnexallymphoma of MALT-type (OAL) [1]. Authors used this therapy onthe basis that, in the Italian experience [2], most cases ofOAL were shown to be related to chlamydial     

Quality of medical care and excess mortality in older patients with mental disorders

BACKGROUND: This study investigated whether differences in quality of medical care might explain a portion of the excess mortality associated with mental disorders in the year after myocardial infarction. METHODS: This study examined a national cohort of 88 241 Medicare patients 65 years and older who were hospitalized for clinically confirmed acute myocardial infarction. Proportional hazard models compared the association between mental disorders and mortality before and after adjusting 5 established quality indicators: reperfusion, aspirin, beta-blockers, angiotensin-converting enzyme inhibitors, and smoking cessation counseling. All models adjusted for eligibility for each procedure, demographic characteristics, cardiac risk factors and history, admission characteristics, left ventricular function, hospital characteristics, and regional factors. RESULTS: After adjusting for the potential confounding factors, presence of any mental disorder was associated with a 19% increase in 1-year risk of mortality (hazard ratios [HR], 1.19; 95% confidence interval [CI], 1.04-1.36). After adding the 5 quality measures to the model, the association was no longer significant (HR, 1.10; 95% CI, 0.96-1.26). Similarly, while schizophrenia (HR, 1.34; 95% CI, 1.01-1.67) and major affective disorders (HR, 1.11; 95% CI, 1.02-1.20) were each initially associated with increased mortality, after adding the quality variables, neither schizophrenia (HR, 1.23; 95% CI, 0.86-1.60) nor major affective disorder (HR, 1.05; 95% CI, 0.87-1.23) remained a significant predictor. CONCLUSIONS: Deficits in quality of medical care seemed to explain a substantial portion of the excess mortality experienced by patients with mental disorders after myocardial infarction. The study suggests the potential importance of improving these patients' medical care as a step toward reducing their excess mortality.     

Unilateral haemorrhagic parenchymal lesions in the preterm infant: shape, site and prognosis

Rademaker KJ, Groenendaal F, Jansen GH, Eken P, de Vries LS. Unilateral haemorrhagic parenchymal lesions in the preterm infant: shape, site and prognosis. Acta Pædiatr 1994;83:602–8. Stockholm. ISSN 0803–5253 In a prospective cranial ultrasound study of 544 infants with a gestational age of 32 weeks or less, 20 (3.6%) infants were diagnosed as having a unilateral parenchymal lesion (PL). Based on the shape of the PL and the evolution on ultrasound, the infants were divided into three groups: group I consisted of 11 infants, in whom the PL was triangular/fan-shaped and separate from the ventricle. The PL evolved into small cystic lesions; group II comprised 3 infants who had a PL with a similar shape, but partially communicating with the ventricle; group III consisted of 6 infants who had a globular-shaped lesion in communication with the ventricle. In groups II and III, the PL evolved into one porcncephalic cyst. The PL was considered to be due to venous infarction in all cases with intraventricular haemorrhage preceding the PL in 7 cases. Sixteen infants survived. A postmortem was performed in 2 of the 4 infants who died, confirming the diagnosis of venous infarction. Neurologicdl sequelae were present in only 2 cases in the first group, while all 6 survivors of the other two groups developed mild to severe hemiplegia. Long-term follow-up was not always available and 4 of the 18 survivors were still less than 18 months when last seen. In 9 of the 11 infants in group I, the PL was localized in the frontoparietal region, while in 8 of the 9 infants in group II or III, the PL was beyond the trigone in the occipital region. The outcome of the unilateral PL is not always unfavourable. It was evident that not only the shape of the lesion and whether or not there was communication with the lateral ventricle, but also the site of the lesion (whether or not it extended into the occipital periventricular white matter) appeared to be important with regard to neurodevelopmental outcome.