Immunomagnetic enrichment, genomic characterization, and prognostic impact of circulating melanoma cells.

PURPOSE: The finding of melanoma cells in the peripheral blood, thus far mainly inferred from the PCR-based demonstration of tyrosinase mRNA, has been associated with metastatic melanoma. Neither the malignant nature nor the prognostic significance of circulating cells could be established. To address this question, we analyzed immunomagnetically isolated circulating melanoma cells for chromosomal aberrations and performed a clinical follow-up study of the enrolled patients. EXPERIMENTAL DESIGN: In a prospective study, blood samples were taken from 164 melanoma patients and 50 donors without malignant disease. Circulating melanoma cells were enriched by immunomagnetic cell sorting using a murine monoclonal antibody against the melanoma-associated chondroitin sulfate proteoglycan. To prove the malignant origin of the positive cells and to define their chromosomal aberrations, we analyzed the genomes of 15 individually isolated cells from seven patients by single-cell comparative genomic hybridization (SCOMP). RESULTS: Absolute and relative frequencies of circulating melanoma cells were associated with stage and with the presence or absence of detectable tumor. The detection of two or more cells correlated significantly with a reduced survival of patients with metastatic melanoma. All of the cells that were analyzed by SCOMP displayed multiple chromosomal changes and carried aberrations typical for melanoma. CONCLUSIONS: Immunomagnetic enrichment enables isolation and genomic characterization of circulating melanoma cells. The prognostic impact on survival of metastatic patients apparently reflects the aggressiveness of an ongoing tumor spread. Direct genomic analysis of the enriched and isolated cells will help to clarify the molecular-genetic basis of the establishment of generalized melanoma.     

Urinary stability of carboxycyclophosphamide and carboxyifosfamide, two major metabolites of the anticancer drugs cyclophosphamide and ifosfamide

Phosphorus-31 nuclear magnetic resonance spectroscopy was used to evaluate the stability of carboxycyclophosphamide (CXCP) and carboxyifosfamide (CXIF) in human urine at pH 7.0 and 5.5 at 25°, 8°, −20°, and −80 °C. At 25 °C and pH 7.0, CXCP and CXIF are relatively stable (≈10% degradation in 24 h). In contrast, they are much less stable at pH 5.5 (≈80% degradation of CXIF and ≈50% degradation of CXCP in 24 h). The rate of degradation of CXCP and CXIF was a function of the storage temperature of the urine samples but, even at −80 °C, was not negligible: ≈30% degradation for CXCP irrespective of pH and ≈40% and 50% degradation for CXIF at pH 7.0 and 5.5, respectively, after storage for 6 months. CXCP was more stable than CXIF at either pH (7.0 or 5.5) and at all storage temperatures (8°, −20°, or −80 °C) of the urine samples. CXCP and CXIF were more stable at pH 7.0 than at pH 5.5, although this difference fell with decreasing temperatures to be almost negligible at −80 °C. To ensure a true estimate of CXCP and CXIF levels, urine samples must be frozen and stored at −80 °C within a few hours of micturition. CXCP and CXIF assays should also be carried out within 2 months and 1 month of storage, respectively. Received: 13 July 1996 / Accepted: 20 January 1997     

The influence of asymmetric quadriceps loading on patellar tracking — An in vitro study

BackgroundIn patients with anterior knee pain and patellar instability, a specific training of the quadriceps muscle – especially the vastus medialis – is often recommended, although the practicability is discussed controversially and the proof of a measurable clinical effect is difficult. Therefore, this in vitro study investigates the influence of asymmetric muscle loading on the motion of the human patella.MethodsSeven human knee specimens were tested in a specially developed knee simulator. During simulated weight-bearing knee flexion, the kinematics of tibia, femur and patella were measured using an ultrasound motion capture system. The quadriceps forces were controlled to achieve a constant ankle force over the whole flexion range which is assumed to represent almost physiological loading. Three different force distributions of the quadriceps were tested — a central, equally distributed load as well as mainly lateral and medial loads.ResultsA significant influence of different quadriceps force distributions was found for patellar tilt around a proximodistal axis (up to 1.7°) and patellar rotation around an anteroposterior axis (up to 3.8°) with respect to the femur. Interestingly, the patellar mediolateral shift was influenced only marginally (< 1.5 mm).ConclusionsSpecific muscle training might help patients with patellofemoral pain and cartilage damage by a slight modification of the kinematics, but we could show that even highly asymmetric quadriceps loads only led to a small alteration of the mediolateral shift in case of a physiologic anatomy of the trochlear groove.     

Disability and quality of life in individuals with postpolio syndrome

Purpose : The purpose of the study is to investigate disability and quality of life in individuals with the characteristic symptoms of postpolio syndrome. Method : Disability is assessed by means of the self-report activities of daily living instrument, and quality of life by means of Kaasa's questionnaire and the quality of life profile. Results : The 39 subjects have on average lived with polio sequelae for 52 years. Their main difficulties are with moving, lifting and carrying. This means restricted mobility, sedentary activities and a need to prioritize. Half of them feel that polio has lessened their possibilities in life, and a quarter have still not accepted the limitations polio has involved. Nevertheless the majority report a high level of psychosocial well-being, and almost a quarter say that living with polio has meant personal development and strength. We found a significant correlation between on the one hand disability with regard to ambulation, arm strength and finger strength on the self-report ADL, and on the other hand the number of negative problems on the quality of life profile (0.33-0.45). Conclusion : The latter instrument needs further testing before its validity can be determined with certainty.     

Psychotic Experiences,Childhood Trauma,and Alcohol-Related Self-Efficacy in a Nonpsychiatric Sample of Individuals in Alcohol Dependence Treatment: A Pilot Study

There is a substantial co-occurrence between alcohol dependence and psychiatric symptoms. Moreover, research suggests that such symptoms, including psychotic experiences, are continuously distributed in the population. There is a lack of research concerning psychotic symptoms in otherwise non-psychiatric populations with alcohol dependence. The aim of this study was to investigate the prevalence of psychotic symptoms in this population, and to relate this to childhood trauma and management of alcohol dependence. From a population with alcohol dependence two sub-groups were extracted, with low and high levels of psychotic experiences respectively. These were compared concerning childhood trauma and management of dependence using ANOVA, and the resulting model was examined using binary logistic regression. There was a sub-group of 14,3% of the population with elevated levels of psychotic experiences. This group displayed higher degree of self-reported childhood trauma as well as difficulties in managing alcohol dependence, when compared to a sub-group with low levels of psychotic experiences. There may be a substantial sub-group in the otherwise non-psychiatric population with alcohol dependence, with significant difficulties concerning psychotic symptoms, trauma and management of dependence, where anxiety may have a mediating function. If so, this group calls for broader assessment and treatment than standard alcohol interventions.     

Work-related skin and airway symptoms among Swedish dentists rarely cause sick leave or change of professional career

Dentistry usually is 'wet work' with risk of damage to the skin barrier, and the hands may be exposed to skin irritants and contact-sensitizing substances used in dental materials or gloves. Airway irritants may also be present. This study assessed the consequences of work-related skin and airway symptoms among dentists in terms of contact with health authorities, sick leave, or changes in the professional career. A questionnaire on these factors was answered by more than 3000 Swedish dentists. Only 6% of the respondents had consulted a physician, although 22% had noted work-related skin symptoms. In 2% the skin symptoms had caused sick leave, and about 2% had reported their skin symptoms as an occupational disease. Two per cent had consulted a physician owing to work-related airway symptoms, which is a minor part of the 13% who had experienced such symptoms when in contact with dental materials. Twenty-five dentists (<1%)had been on sick leave because of work-related airway symptoms. Only 19 dentists reported change of activities or occupation owing to work-related skin or airway symptoms, and in most cases these symptoms only contributed to their decision. In summary, whereas sick leave in dentists because of musculoskeletal problems may be common, the present study shows that this is not the case for workrelated skin or airway symptoms, and such symptoms seldom affect the dentists' professional career.