The role of cytogenetics in the classification of soft tissue tumours

 Soft tissue tumours represent a heterogeneous group of mesenchymal lesions, and their classification is the subject of continuous debate. Chromosome analysis, molecular cytogenetics and molecular assays may become increasingly useful in diagnosis, and this review summarises advances in the cytogenetic characterisation and classification of soft tissue tumours. Among the group of fibrous lesions, superficial fibromatosis exhibits trisomy 8. This genomic change is also observed in desmoid fibromatosis in association with trisomy 20. Trisomy 11 is the most frequently observed chromosomal aberration in congenital fibrosarcoma. Dermatofibrosarcoma protuberans and giant cell fibroblastoma share a translocation t(17;22), which supports the concept of the existence of a common differentiation pathway. Adipose tissue tumours is the group in which integration of genetics and pathology has been most fruitful. Ordinary lipomas cytogenetically show an abnormal karyotype in about half the cases. Genomic changes of the 11q13 region are observed in hibernoma. Lipoblastoma exhibits a specific 8q rearrangement in 8q11-q13. Loss of material from the region 16q13-qter and 13q deletions are observed in spindle cell/pleomorphic lipomas. The well-differentiated liposarcoma/atypical lipoma group is characterised karyotypically by the presence of one extra ring and/or extra giant chromosome marker. Myxoid and round cell liposarcoma share the same characteristic chromosome change: t(12;16)(q13;p11) in most cases. In the group of smooth muscle lesions most data are derived from uterine leiomyomas, which can be subclassified cytogenetically into seven different types. Half of all leiomyomas are chromosomally normal; the other half have one of six possible consistent chromosome changes. Alveolar rhabdomyosarcoma is characterised cytogenetically by two variant translocations t(2;13)(q35;q14) and t(1;13)(p36;q14). Among tenosynovial tumours, the localised type of giant cell tumour of tendon sheath exhibits two different karyotypic changes. One involves 1p11 in a translocation with chromosome 2 or with another chromosome. A second type involves 16q24. Synovial sarcoma is characterised cytogenetically by a translocation occurring between chromosome 18 and presumably two adjacent loci on the X chromosome. In neural tumours, abnormalities of chromosome 22 have been reported in benign schwannomas and perineuriomas. Malignant peripheral nerve sheath tumours exist in two main forms: sporadic and associated with the NF-1 syndrome. Karyotypes are very complex, but chromosomes 17q and 22q are very often involved. Clear cell sarcoma is characterised cytogenetically and molecularly by a translocation t(12;22)(q13;q12). The Ewing’s sarcoma/peripheral neuroectodermal tumour category shows a central karyotypic anomaly represented by the translocation t(11;22). The two variants t(21;22) and t(7;22) are found in some cases. Among cartilaginous lesion, the most frequently described anomaly is the t(9;22)(q22;q12) in extraskeletal myxoid chondrosarcoma. Intra-abdominal desmoplastic small round cell tumour is characterised by a t(11;22)(p13;q12). Received: 5 February 1997 / Accepted: 24 February 1997     

Electrophysiological properties of the propafenone-analogue GE 68 (1-[3-(phenylethyl)-2-benzofuryl]-2-(propylamino)-ethanol) in isolated preparations and ventricular myocytes of guinea-pig hearts

GE 68 ((Rac.)-1-[3-(Phenylethyl)-2-benzofuryl]-2-(propylamino)-ethanol hydrochloride) is structurally related to propafenone, and exerts negative inotropic and negative chronotropic effects similar to the parent drug, but lacks any β-adrenoceptor blocking activity contrary to propafenone. Thus, the electrophysiological effects of GE 68 were studied in papillary muscles, left atria, Purkinje fibres, sinoatrial nodes and ventricular myocytes of the guinea-pig heart with the intracellular microelectrode technique and the patch-clamp technique in the cell-attached mode. The decrease of the maximum upstroke velocity (V˙_max) by GE 68 (1 to 10 μM) was use- and frequency-dependent. V˙_max recovered from the use-dependent block with a time constant of 4.1 ± 0.6 s. In papillary muscles and Purkinje fibres action potential duration was shortened, while it was prolonged in left atria and sinoatrial nodes. Half-maximal steady-state inactivation of the sodium channels was shifted to more negative membrane potentials (control: –91.5 ± 0.8 mV, 10 μM GE 68: –97.9 ± 2.5 mV). The peak of the current-voltage relationship and the reversal potential were not changed by GE 68. The amplitude of the unitary current remained unaltered, while open state probability was decreased. The most striking effect of GE 68 was an increase of the number of sweeps without single channel openings (1 μM: 2 fold, 10 μM: 6 fold). GE 68 also caused a decrease of the mean open times, and an increase of the mean closed times in unmodified and pronase-modified sodium channels. Besides the lack of β-adrenoceptor blocking activity, data present a faster recovery from the use-dependent block by GE 68 and a lower affinity to inactivated sodium channels compared to the reference drug propafenone, as well as differences in the effect on single channel kinetics. Received: 25 July 1996 / Accepted: 14 October 1996     

COMPARISON OF TWO COMMERCIAL TEST KITS FOR QUANTIFICATION OF SERUM CARBOHYDRATE-DEFICIENT TRANSFERRIN

Serum levels of carbohydrate-deficient transferrin (CDT) weremeasured in subjects of two independent studies using two differentcommercial kits. The kits measure CDT either as a percentageof total transferrin (AXIS %CDT^TM, AXIS Biochemicals AS, Norway),or as the absolute amount (CDTect^TM, Pharmacia, Sweden). Ina population of males (mean age 41 years) consisting of alcoholics,heavy, moderate and non-drinkers, a strong correlation was foundbetween AXIS %CDT and CDTect results (r=0.92, n=58, P<0.001).Sensitivity and specificity in detecting chronic alcoholic drinkingof over 60 g/day were 78 and 94% for the AXIS assay, and 83and 88% for the CDTect assay, respectively. In a populationfrom a birth cohort study, consisting of 21-year-old males andfemales with less excessive alcohol consumption, the correlationbetween AXIS %CDT and CDTect CDT was weaker but still statisticallysignificant (r=0.46. n=212, =<0.001). In this population,with specificities >83% in detecting alcohol consumptionlevels of     

A study of the relationship between ambient lead and blood lead among lead battery workers

 Objective: To examine the relationship between ambient lead levels and blood lead levels and to explore the modifiers of the relationship between ambient lead and blood lead. Method: A cross-sectional study was conducted in two lead battery factories. Blood lead level and ambient lead concentration were measured for each participant concurrently. A structured questionnaire was administered to collect sociodemographic characteristics and occupational history. Design: Biological and personal environmental measurements of 219 lead-exposed workers were analyzed by both simple and multiple linear regression. A regression model was selected for interpretation. Results: A high correlation (r=0.62) between ambient lead (PbA) and blood lead (PbB) was observed. In addition, numerous factors, including age, sex, alcohol consumption, personal hygiene practice and type of lead exposure, were also found to influence blood lead levels. Although PbB was highly correlated with PbA, blood lead level may not be effectively lowered by reducing ambient lead level. Based on the regression coefficients, improvement of hygienic practice was more effective at lowering PbB than reducing ambient lead level. Good hygienic practice may be the preferential way to reduce lead exposure in current conditions. Conclusion: Education of correct work practice may be more important than engineering control in the developing countries to lower blood lead levels in lead battery factories. Received: 28 May 1996/Accepted: 30 August 1996     

Le traitement du signal en électromyographie: mise au point

Automatic analysis of electromyography (EMG) signals, first operated in 1950 with analogic machines, steeply expanded from 1980 when fast computers and worthwhile programs became available. On-line measurement of response area and latency, averaging of low amplitude waves, fast sorting of motor unit potential shape parameters, computation of the “jitter” between two muscle fibers, turns/amplitude and spectral analysis of interferential pattern records, are some examples of programs currently offered in modern EMG machines. Other techniques are still reserved for research purposes: scanning EMG, decomposition of nerve and muscle compound potentials, measurement of the threshold and firing rate of motor units, trace analysis using tracking models. Finally, the credit for artificial intelligence systems (knowledge based systems, fuzzy logic, neuronal networks) is still not clearly stated.     

A comparison of clinical and research DSM-III-R diagnoses of schizophrenia in a Finnish national birth cohort

As a prerequisite to the use of the Finnish National Hospital Discharge Register in psychiatric epidemiological research, we studied the diagnostic reliability of the register in terms of the psychiatric morbidity experienced by a national birth cohort. We investigated all entries to the register for a sample based upon the Northern Finland 1966 birth cohort at the age of 16 years (n=11017). Until the end of 1993 (age 27 years), a total of 563 subjects had a register diagnosis indicating a psychiatric illness, 37 of them being schizophrenia. When operational criteria (DSM-III-R) were applied to clinical information in the available original hospital records for cases of psychosis, personality disorder and substance abuse (n=249), 71 fulfilled criteria for schizophrenia, including all of the 37 cases in the register and an additional 34 (48% false-negatives), most frequently diagnosed in the register as schizophreniform or other psychosis. Despite the official use of DSM-III-R nomenclature, it appears that the clinical concept of schizophrenia in Finland, manifest within the register, remains very restrictive. The application of operational criteria is a necessary prerequisite for scientific research on schizophrenia.