Atrioventricular block complicating dissecting aneurysm of the aorta

A 67-year-old patient who presented with acute dissecting aneurysm of the aorta was complicated by progressive transient atrioventricular heart block. Post-mortem examination findings confirmed the diagnosis of dissection of the ascending aorta and revealed an interatrial haemorrhage in the area of the septal atrioventricular junction.     

MicroRNA expression differentiates between primary lung tumors and metastases to the lung

For surgical pathologists, distinguishing whether a pulmonary neoplasm is primary or metastatic can be challenging, and current biomarkers do not always aid lung tumor classification. The tissue-associated expression of microRNA likely explains the remarkable finding that many tumors can be classified based solely on their microRNA expression signature. Here we show that microRNAs can serve as biomarkers for lung tumor classification. Using microRNA microarray data generated from 76 formalin-fixed, paraffin-embedded (FFPE) samples of either primary lung cancer or metastatic tumors to the lung, we have identified a set of microRNAs expressed differentially between these two groups. This set includes hsa-miR-182, which was most strongly over-expressed in the lung primary tumors, and hsa-miR-126, which was over-expressed in the metastatic tumors. The differential expression of this set of microRNAs was confirmed using qRT-PCR on a set of 54 samples. In light of our data, microRNA expression should be considered as a potential clinical biomarker for surgical pathologists faced with discerning the tumor type of an inscrutable lung neoplasm.     

Neutron therapy in cervical cancer: results of a phase III RTOG Study

Between October 1976 and May 1984, 156 patients with locally advanced cervical cancer were entered into a Phase III trial with the participation of five institutions. Patients were randomly assigned to receive photons only (50 Gy in 25 fractions over 5 weeks plus intracavitary applications or external-beam boost) or mixed-beam radiotherapy (2 fractions a week of neutrons, 3 fractions a week of photons to a total RBE-adjusted dose of 50 Gy over 5 weeks plus intracavitary applications or external mixed-beam boost). Only patients with squamous carcinoma of FIGO Stages IIB, III, or IVA with negative para-aortic nodes on lymphangiogram were eligible. Ten patients were excluded from the analysis because of ineligibility or cancellation. Of the 146 patients analyzed, 80 were treated with mixed-beam radiotherapy and 66 with photons. Patients were grouped by stage and institution. The percentage of patients undergoing intracavitary applications was 50% on mixed beam and 75% on photons (p less than 0.01). Tumor clearance was 52% and 72% for mixed beam and photons, respectively (p less than 0.03). Local control at 2 years was 45% for mixed beam and 52% for photons. Median survivals were 1.9 years on mixed beam and 2.3 years on photons. Severe complications occurred in 19% and 11% in mixed beam and photons respectively (p less than 0.13). The inferior outcome with neutron therapy in this study may have resulted from the use of horizontal neutron beams of varying energy and penetration. A new randomized trial using high-energy hospital-based cyclotrons with gantry-mounted beam-delivery systems has recently been activated to evaluate more rigorously the role of fast-neutron therapy for advanced cervical cancer.     

Wilmss' tumor: The northern israel oncology institute experience

Between 1971 and 1992, 42 children (median age = 2 years) with histologically proven Wilms' tumor were evaluated at the Northern Israel Oncology Institute. Most patients were staged according to National Wilms' Tumor Study (NWTS) criteria by which 18 were clinical stage I-II and 24 were III-IV. Combined therapy (surgery, chemotherapy, and radiotherapy) was given with a change to lower dose radiotherapy (<2,000cG) after 1981. The pre-1981 group (13 patients) suffered six relapses, most of which were pulmonary, whereas the 1981-1992 group (29 patients) had three relapses. The actuarial 5-year survival rate using Kaplan-Meier tables was 79% for the entire group but 100% for the 1981-1992 group and 38% for the 1971-1980 group. One case of immediate hepatic toxicity and one sudden death, unknown cause, of a patient in remission occurred in the group. Late deleterious effects were seen in five other patients; four had scoliosis and one developed osteoid osteoma of a rib. Despite these encouraging results, the necessity of ongoing monitoring for further longterm toxicities is apparent.     

Neuropsychological sequelae of childhood cancer in long-term survivors

In order to assess the effects of various cancer treatments on neuropsychological functioning, 74 long-term survivors of childhood cancer were examined. A comprehensive battery of tests was administered to two CNS treatment groups (irradiated and nonirradiated leukemia and lymphoma patients) and a control group (solid tumor and Hodgkin disease patients receiving no CNS treatment). The CNS-irradiated group obtained lower scores than the other two groups, with significant differences in visual-motor and fine motor skills, spatial memory, and arithmetic achievement resulting in significant differences in IQ scores (VIQ, PIQ, FSIQ). The results are discussed in relation to: (1) the effects of CNS irradiation on cognitive development; (2) the specificity of these effects; and (3) the relationship of age at diagnosis to treatment effects. It is concluded that although there is a general lowering of scores after CNS irradiation, the effect is most pronounced for nonlanguage skills. Age at diagnosis was less important than the type of treatment, with CNS irradiation reducing performance regardless of when cancer was diagnosed. There were indications that children with any type of cancer diagnosed before age 5 years are more likely to have some cognitive difficulties.     

Male reproductive function in long-term survivors of childhood cancer

We evaluated reproductive function in 27 male long-term survivors of childhood cancer treated during the prepubertal and pubertal period. Sperm samples were obtained from 23 patients; four who refused to provide specimens indicated that they had fathered normal healthy children. Thirteen patients were 12 years old or younger at the time of diagnosis and initiation of therapy. Chemotherapy was calculated according to the cumulative amount of drug administered and correlated with the surface area. Sterility was associated with large doses of single alkylating agents or reduced doses administered with other agents in combination regimens. It was noted in boys treated in both the prepubertal and pubertal period. Sterility was also observed in patients who received testicular radiation alone or in combination with chemotherapy. However, it was not an inevitable consequence in all patients, despite treatment with similar or identical regimens. Fertility potential could not be predicted by clinical examination (testicular size) or gonadotrophin and testosterone values. The results were compared to published reports of treatment-induced sterility in adult males. Additional investigations are required to establish more accurate correlations of dosage with reproductive potential.     

Novel dual inhibitors of AChE and MAO derived from hydroxy aminoindan and phenethylamine as potential treatment for Alzheimer's disease

Carbamate derivatives of N-propargylaminoindans (Series I) and N-propargylphenethylamines (Series II) were synthesized via multistep procedures from the corresponding hydroxy precursors. The respective rasagiline- and selegiline-related series were designed to combine inhibitory activities of both acetylcholine esterase (AChE) and monoamine oxidase (MAO) by virtue of their carbamoyl and propargylamine pharmacophores. Each compound was tested for these activities in vitro in order to find molecules with similar potencies against each enzyme. Compounds with such dual AChE and MAO inhibitory activities are expected to have potential for the treatment of Alzheimer's disease. The observed SAR also offers insight into the requirements of the active sites on these enzymes. A carbamate moiety was found to be essential for AChE inhibition, which was absent in the corresponding hydroxy precursors. The propargyl group caused 2-70-fold decrease in AChE inhibitory activity (depending on the position of the carbamoyl group) of Series I, but had little or no effect in Series II. Thus, the 6- and 7-carbamyloxyphenyls in Series I were either equipotent to, or slightly (2- to 5-fold) less active as AChE inhibitors than, the corresponding compounds in Series II, while the 4-carbamyloxyphenyls were more potent. The presence of the carbamate moiety in 6- and 7-carbamyloxyphenyls of Series I, considerably decreased MAO-A and -B inhibitory activity, compared to that of the parent hydroxy analogues, while the opposite was true for Series II. Thus, the 6- and 7-carbamyloxyphenyls in Series I were 2-3 orders of magnitude weaker MAO inhibitors while the 4- carbamyloxyphenyls were equipotent with the corresponding compounds in Series II. In both series, N-methylation of the propargylamine enhanced the MAO (A and B equally) inhibitory activities and decreased the AChE inhibitory activity. Two candidates belonging to the indan and tetralin ring systems (24c, 27b) and one phenethylamine (53d) were identified as possible leads for further development based on the following criteria: (a) comparable AChE and MAO-B inhibitory activities, (b) good to moderate AChE inhibitory activity, and (c) lack of strong MAO-A selectivity. However, it is likely that these compounds will be metabolized to the corresponding phenols, with inhibitory activities against AChE and/or MAO-A or -B, different from those of the parent carbamates. Thus, the apparent enzyme inhibition will be a result of the combined inhibition of all of these individual metabolites. The results of our ongoing in vivo screening programs will be published elsewhere.