Malignant mesothelioma is a rare malignancy with a median survival, ranging from 4 to 18 months in untreated patients. In a phase II study of patients with mesothelioma, the efficacy and toxicity of ...ifosfamide and mesna was evaluated. Twenty-nine previously untreated patients, with histologically proven and unresectable mesothelioma, entered the study. Three patients were later excluded from the study due to revision of the diagnoses. The patients had to have bidimensionally measurable disease by CT scans and a WHO performance status ≤3. Eligible patients received ifosfamide 3000 mg/m
2 per day for 3 days as a 1-h infusion and mesna 1800 mg/m
2 per day for 3 days every third week. Dose modifications were made according to the degree of hematologic, neurologic and renal toxicity. Response to treatment was evaluated in accordance with WHO criteria. The median age of patients was 59 years (range 39–68), 18 patients (69%) had a history of asbestos exposure and the median of treatment cycles was four (range 1–10). No complete responses were observed. One patient obtained a partial response after five cycles with a duration of response of 25 months. Nine patients (35%) had stable disease, while 13 (54%) progressed. The median survival for all patients was 10 months. The toxicity of the treatment was considerable. Thirteen patients (50%) had grade 4 leucopenia, ten patients (38%) had grade 3 or 4 reversible neurotoxicity and ten patients (38%) had grade 3 or 4 nausea and vomiting. Eleven patients (42%) went off the study due to the toxicity of the treatment. In conclusion, ifosfamide did not show any substantial activity of relevance in malignant mesothelioma at the dose level investigated, in spite of considerable toxicity.
Functional magnetic resonance imaging was used to detect cortical activation in the right and left perisylvian cortex of seven young adult right-handed volunteers in response to a letter fluency task ...and to a visual naming task using standardized line drawings. Both letter fluency and visual naming activated left dorsolateral prefrontal cortex (Brodmann's areas 6, 9, 44 and 45). Only visual naming activated area 37 (a cortical region with strong connections to visual association areas), visual association area 19, and areas 39 and 21 previously shown to activate with auditory semantic tasks. This study supports a role for area 37 as participant in a visual lexicosemantic processing network which may otherwise overlap the auditorysemantic network.
The master two-dimensional (2-D) gel database of human keratinocytes currently lists 3154 cellular proteins (2224 isoelectric focusing, IEF; and 930 nonequilibrium pH gradient electrophoresis, ...NEPHGE), many of which correspond to post-translational modifications. 1082 polypeptides have been identified (protein name, organelle components, etc.) using a procedure or a combination of procedures that include (i) comigration with known human proteins, (ii) 2-D gel immunoblotting using specific antibodies, (iii) microsequencing of Coomassie Brilliant Blue stained proteins, (iv) mass spectrometry, (v)vaccinia virus expression of full length cDNAs, and (vi) in vitro transcription/translation of full-length cDNAs. This year, special emphasis has been given to the identification of signal transduction components by using 2-D gel immunoblotting of crude keratinocyte lysates in combination with enhanced chemoluminescence (ECL) detection. Identified proteins are listed both in alphabetical order and with increasing SSP number, together with their M(r), pI, cellular localization and credit to the investigator(s) that aided in the identification. Ultimately, the aim of the comprehensive database is to gather--through a systematic study of ekeratinocytes--qualitative and quantitative information on proteins and their genes that may allow us to identify abnormal patterns of gene expression and to pinpoint signaling pathways and components affected in various skin diseases, cancer included.
The expression of T-cell surface antigens was investigated in the cerebrospinal fluid (CSF) and peripheral blood of 11 patients with multiple sclerosis, 6 patients with aseptic meningitis, and 16 ...healthy subjects. A panel of monoclonal antibodies to adhesion and activation proteins was used in combination with an anti-CD3 antibody in dual-color flow cytometry. The problem of low cell numbers in the CSF from normal individuals was overcome by use of a modified staining procedure in microtiter plates, enabling analysis of as few as 5,000 cells. The majority of T cells in the CSF of the three patient groups exhibited the phenotype of memory cells (CD45RO+). CSF T cells also expressed significantly higher levels of several adhesion and activation molecules, including very late activation (VLA) antigens 3 through 6, lymphocyte function-associated (LFA) antigen 1, LFA-3, CD2, CD26, and CD44. Comparison between the different categories revealed that peripheral blood T cells from patients with multiple sclerosis expressed significantly lower amounts of the VLA integrins 4 and 5 as well as their common beta subunit CD29, compared with normal control subjects. No differences between patients with multiple sclerosis and control subjects could, however, be seen regarding the distribution of memory/naive cells or CD4+/CD8+ cells in peripheral blood. Our data support a hypothesis that memory T cells with a high expression of several adhesion molecules are selectively recruited to the central nervous system compartment, under both pathological and normal conditions.
Valid generalizations of results from population-based epidemiological surveys requires knowledge about how representative the sample is. The Copenhagen Center for Prospective Population Studies have ...assessed mortality on the basis of pooled data from three research programmes in the region of Copenhagen. In two of the studies, subjects were randomly selected, using the Danish Central Population Registry, within certain age groups and area-restricted sectors of the Greater Copenhagen. In the third study, men employed in 14 companies participated. Participation rates were between 78% and 87% in the three programmes. Standardized mortality rates (SMR) were calculated in relation to mortality rates in the municipality of Copenhagen and in the whole country in three age groups and the two genders. SMR values in the whole sample including non-participants were similar to rates for Copenhagen in the Copenhagen City Heart Study, whereas mortality rates in the Glostrup Population Studies were similar to rates for the whole country. The mortality rates among participants were lower than in the whole sample, and differences existed in relation to region and selection criteria of the cohorts. The Copenhagen Male Study, where only employed men were included, showed the lowest mortality rates, and higher rates were found in the study from the central part of the City (the Copenhagen City Heart Study) compared to the study from the suburbs (the Glostrup Population Studies). The difference between mortality rates in the cohorts and in Copenhagen City decreased with increasing age. The SMR converged towards 1.00 with increasing observation time. In conclusion, high participation rates were found in all three studies, resulting in SMR values for participants only slightly lower than in the source population in the two randomly selected samples, but 30% lower values in the sample of employed men. As mortality rates in the total samples including non-participants were markedly higher than among the participants, generalizations of results for participants to the whole population should be made with caution, especially during the first years of observation.
A prospective, observational survey.
To describe lower urinary tract symptoms in uncomplicated lumbar root compression syndromes with special reference to prevalence, nature, and severity, and to ...analyze whether the occurrence of lower urinary tract symptoms correlates with age, pain, analgesic intake, or the type and level of compression.
Lower urinary tract symptoms with lumbar root compression are well known in the classic but rather rare cauda equina syndrome. However, micturition difficulties seem to be far more frequent in lumbar root compression syndromes.
One hundred eight male patients admitted for surgery for lumbar disc herniation or spinal stenosis were investigated with an extensive questionnaire about their micturition.
Fifty-five percent had significant lower urinary tract symptoms. Eighty percent of the patients with spinal stenosis had symptoms. Thirty-three patients had irritative symptoms, 36 had obstructive symptoms, and 23 had retention symptoms. Twenty-four had severe symptoms. Median compression resulted in more symptoms than paramedian compression. There was no correlation between age, level of compression, drug intake, or pain score and lower urinary tract symptoms.
Lower urinary tract symptoms of mixed type occur with a high prevalence in male patients with lumbar root compression syndromes referred for neurosurgical evaluation and treatment.
Numerical optimization is commonly used for the design of reflector antennas that produce a contoured beam. The optimization problems that arise in this context are generally nonlinear and difficult ...to solve to global optimality. Different problem formulations lead to different properties and challenges. We demonstrate that the popular minimax approach can have many local minima and that a local optimization method with a poor initialization may result in a bad design. As an alternative to the minimax approach, we propose a one-sided least-squares formulation. We outline a trust-region method for finding a local minimum, and we illustrate the merits of the new approach with some numerical examples. In particular, our preliminary results indicate that our method is often less sensitive to the initial design than the minimax method. Finally, we investigate the use of the one-sided least-squares model as a means to find an initial guess for the minimax approach, and our results show that it sometimes leads to a better local minimum, and hence improves the design.
Background. Local recurrence is one of the major problems in treatment of breast cancer. Approximately 20% of patients who have radical or modified radical mastectomy have a local recurrence.
...Methods. The records of 98 women with locally recurrent breast cancer treated with wide local excision, in the years 1983–1987, were reviewed. The median age at excision was 62 years (range, 32–84 years). All patients were observed until death or December 31, 1989. The median follow‐up period was 36 months (range, 2–79 months).
Results. At follow‐up, 44 of 98 patients (45%) had had a new local relapse and 47 of 98 (48%) were dead. The median duration of local control for all patients was 21 months (range, 1–79 months). The diameter of the local recurrence seemed to influence the duration of local disease control but not total survival. Patients admitted directly for surgery had a longer period of local control compared with patients admitted after unsuccessful oncologic treatment of the local recurrence. The 5‐year local control rates were 50% and 24%, respectively (P > 0.92). No statistically significant difference in local control could be shown whether or not the patient received additional oncologic therapy in continuity with the wide local excision. The 5‐year local control rate in patients treated only by surgery was 33% compared with 42% in patients also receiving additional oncologic treatment (P > 0.63).
Conclusions. Wide local excision of recurrent breast cancer seems to provide as good or even better local control than other treatment modalities. Surgery should not be postponed in cases of ineffective medical treatment or radiation therapy.
Objective. The purpose of this study is to investigate the influences of visual feedback on power performance during leg press.
Design. The research was conducted as an experimental procedure with a ...cross-over design.
Setting, participants and main outcome measures. Sixteen, elite, female, field hockey players aged 16–27 years were randomly assigned to two groups. Both groups were tested with and without visual feedback, but in the reverse order. The test protocol consisted of familiarisation followed by two test trials. The visual feedback was produced by and displayed on a computer that was used to record the power output.
Results. Power performance was significantly better with visual feedback than without visual feedback (
p=0.027). There was no significant interaction between the testing order, suggesting no carry over effect (
p=0.212).
Conclusion. Visual feedback has a significant positive effect on the power performance of elite, female, field hockey players using a leg press.
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