Chromosome aberrations in nine patients with ovarian cancer

Cytogenetic analysis was performed on 13 tumor specimens (six solid tissues and seven effusions) from nine patients with various types of ovarian cancer. Eight of these patients had not received cytotoxic therapy prior to the initial karyologic assessment. Extensive and complex numerical and structural alterations were seen in nearly all specimens. Consistent (clonal) abnormalities were found in each case, but karyotypic heterogeneity within a tumor was a consistent finding in this series. Aberrations of chromosomes 1, 3, 6, 7, 10, and 12 were each observed in five or more patients. Although no specific recurring translocations were observed, partial deletions of 3p, 6q, 8p, and 10q were each seen in three different cases. Breakpoints tended to recur at several chromosomal band regions, some of which appear to be near the known loci of certain protooncogenes. Double minute chromosomes were seen in one patient, and a homogeneously staining region was found in another. Karyotypic analysis was performed on one patient both before and after initiating chemotherapy, and the chromosome pattern became more complex after treatment. Overall, our findings indicate that karyotypes in newly diagnosed, untreated patients with ovarian cancer can be extremely complicated, and that the extent of chromosome change may increase with tumor progression. Furthermore, the recurrence of specific regional chromosome losses suggests that these sites contain genes whose loss plays a role in the formation of some ovarian tumors.     

The origin of human B and T cells from multipotent stem cells: a study of the Tn syndrome

The Tn (or polyagglutinability) syndrome corresponds to a human nonmalignant acquired condition which results from a somatic mutation occurring at the level of bone marrow stem cells. This model offers therefore a unique opportunity to study the contribution of multipotential stem cells to the maintenance of cells from the lymphoid lineage. We found that the Tn mutation is expressed by both myeloid and lymphoid mature blood cells. Whereas a large proportion of surface IgM-bearing B cells carry the Tn mutation, only a small percentage of T cells and IgA- or IgG-bearing B cells are defective, showing that under physiological conditions the penetration of stem cells into the various myeloid and lymphoid compartments is variable.     

Thyroid carcinoma mimicking a toxic adenoma

A young woman with a thyroid papillary carcinoma behaving as an autonomously hyperfunctioning nodule is described. Only 17 similar patients have been seen in the past 25 years. It is emphasized that hyperthyroidism does not exclude malignant disease in hot nodules. This possibility suggests that all thyroid nodules, either cold or hot, require careful management. Therefore, in at risk cases, surgery could be the most useful treatment.     

An open-randomized clinical trial of selegiline in amyotrophic lateral sclerosis

Based on the hypothesis that free radicals play a general role in the neurodegenerative process in motor neuron disease, we tested selegiline in a group of patients affected by amyotrophic lateral sclerosis (ALS) to examine whether it might modify the progression of the disease. Patients were admitted if they were 25–80 years old and had a confirmed diagnosis of ALS with symptoms lasting no longer than 24 months. Patients with familial ALS, pure progressive bulbar palsy, primary lateral sclerosis or progressive muscle atrophy were excluded; a total of 111 patients were recruited. Fifty-three patients were randomly assigned to receive the drug (selegiline 10 mg/day orally for 6 months) and the remaining 58 were considered ALS controls. Mortality was similar in the two groups (4 and 5 patients respectively), though the difference was not statistically significant. Among the survivors, mean MRC and Norris disability scores and forced vital capacity were fairly similar in the two groups at all times and no statistically significant difference between treated and untreated patients was found. The results did not change when the data were related to age, duration and characteristics of onset of the disease. The rate of progression was significantly more rapid in patients with bulbar symptoms in both groups. Our data do not show any significant effect of selegiline in modifying the progression of ALS.     

Inter-relation between "classic" motor neuron disease and frontotemporal dementia: neuropsychological and single photon emission computed tomography study.

The purpose of this study was to examine the possible association between "classic" motor neuron disease (cMND) and frontotemporal dementia (FTD), using neuropsychological evaluation and single photon emission computed tomography (SPECT). Psychological tests assessing language, perceptuospatial, memory, and "frontal lobe" functions were given to patients with cMND and test scores were compared with those of normal control subjects. 99mTc-HMPAO SPECT was performed on patients with cMND, FTD and motor neuron disease (FTD/MND), FTD alone, and normal control subjects. Regional cerebral blood flow indices (rCBFi) were determined in 36 cortical regions, and differences between grouped rCBFi data were investigated by canonical discriminant analysis. There were significant group differences in the scores of picture sequencing and token tests in patients with cMND compared with normal controls. Regional CBFi data showed frontal and anterior temporal reductions in patients with cMND compared with normal controls. A similar pattern of SPECT abnormality was seen in patients with FTD/MND and FTD alone, but to a more pronounced degree than in patients with cMND. Neuropsychological and SPECT findings in cMND, FTD/MND, and FTD showed a common pattern of cerebral involvement, most pronounced in the second two conditions. It is suggested that cMND, FTD/MND, and FTD represent a clinical range of a pathological continuum.     

On the road to collaborative treatment planning: Consumer and provider perspectives

Although consumers have made significant gains in having their voices heard in several areas within mental health, they have made less progress in being able to collaborate with their own treaters in setting treatment goals. On the basis of several years of groundwork by staff at the Connecticut Mental Health Center (CMHC), the Patient Care Committee conducted a needs assessment of providers and consumers to assess both groups' current involvement, interest in, and attitudes toward collaborative treatment planning. The results indicate that providers tend to place much of the responsibility for the difficulties in implementing collaborative treatment planning on consumers. Also, providers tend to underestimate consumers' interest in participating in this process. Implications of these findings for the development of an agency-wide training to enhance the collaborative nature of treatment planning are discussed.     

The "Will Rogers effect" on stage grading

Will Rogers phenomenon affects survival statistics applied to clinical research and could determine a misreading of results. Stage migration due to new methods of diagnostic imaging and staging invasive procedures could improve actuarial survival in each stage. TNM System is impaired when survival rates come from different inhomogeneous countries, regions and eras. Randomized trials suffer this fallacious phenomenon when staging depends on the different treatments which are to be evaluated.     

Classification of childhood epilepsy syndromes in newly diagnosed epilepsy: interrater agreement and reasons for disagreement

PURPOSE: The International League Against Epilepsy (ILAE) classification of the epilepsies is in increasingly widespread use. The following analysis was done to assess the interrater agreement in classifying epilepsy syndromes in children with newly diagnosed epilepsy. METHODS: In a prospective, community-based study, 613 children with newly diagnosed epilepsy were recruited. Based on information available at diagnosis or generated as part of the initial diagnostic assessment, three pediatric neurologists independently classified epilepsy syndromes. Interrater agreement was assessed with kappa. RESULTS: Interrater agreement was extremely good, with kappa scores > or = 0.80 for almost all comparisons. Relatively limited quality of the EEG and seizure information in some cases, as well as discrepancies between the two, were associated with a tendency for more disagreement. CONCLUSIONS: A high degree of interrater agreement was obtained in this study, indicating that the system for classifying syndromes can be meaningfully used in a community-based sample. Quality of the information, which is often, by necessity, less than optimal in newly diagnosed epilepsy, is a potential barrier to identification of syndromes. A substantial proportion of children were classified into relatively nonspecific syndromes. Over time, additional information may come to light to allow more precise identification of their forms of epilepsy. In an epidemiologic setting, the ILAE classification of the epilepsies can be successfully used with a high degree of reliability to classify newly diagnosed epilepsy in children.     

Evaluation and prediction of drug permeation

A major challenge confronting the pharmaceutical scientist is to optimize the selective and efficient delivery of new active entities and drug candidates. Successful drug development requires not only optimization of specific and potent pharmacodynamic activity, but also efficient delivery to the target site. Following advances in rational drug design, combinatorial chemistry and high-throughput screening techniques, the number of newly discovered and promising active compounds has increased dramatically in recent years, often making delivery problems the rate-limiting step in drug research. To overcome these problems, a good knowledge of the pharmacokinetic barriers encountered by bioactive compounds is required. This review gives an overview of the properties of relevant physiological barriers and presents some important biological models for evaluation of drug permeation and transport. Physicochemical determinants in drug permeation and the relevance of quantitative and qualitative approaches to the prediction and evaluation of passive drug absorption are also discussed.     

Patients' and doctors' perception of long-term morbidity in patients with testicular cancer clinical stage I

Patient-based questionnaires were designed with the aim to identify and rank long-term somatic and psychosocial morbidity in patients with low-stage testicular cancer. A further intention was to compare patients' assessments with experienced doctors' general opinion on quality of life items in cured testicular cancer patients. In pilot study I, 103 tumour-free patients ranked items of physical and psychosocial morbidity after having had various kinds of treatment. Though the ranking procedure appeared to cause some difficulties amongst the patients and subsequently was abandoned, the results indicated considerable differences between the patients' and doctors' evaluations. In pilot study II patients were asked to score the different items. The questionnaire of pilot study II was completed by 107 patients from the Norwegian Radium Hospital (NRH) and 99 relapse-free patients from the Royal Marsden Hospital (RMH) with testicular cancer stage I at least 1 year after infradiaphragmatic radiotherapy (n = 94) or adjuvant chemotherapy (2 cycles,n=26), or patients who had been followed on the surveillance program (n = 86). A total of 93 doctors completed a similar questionnaire, thereby expressing their general opinion on long-term morbidity in comparable testicular cancer patients as seen during routine clinical follow-up. Both the irradiated patients and those on the surveillance program reported slight degrees of Raynaud-like phenomena, neurotoxicity and ototoxicity, most probably representing background morbidity in an age-matched general male population. Doctors tended to underestimate their patients' somatic morbidity, but often overestimated the degree of psychological distress, in particular in patients on the surveillance program. Significant differences between RMH and NRH patients with regard to sexual problems and to leisure time activity may be explained by cultural differences in the two countries. The items presented in the questionnaire used identify important issues for patients cured of testicular cancer which may be used in future multicentre trans-cultural studies assessing these patients' quality of life. This will provide sufficient data for psychometric testing and, together with the findings from patients' free comments, support the final design of a testicular cancer quality of life module.