Malignant lymphoma. Pathology, diagnosis, therapy

Summary Malignant lymphomas can be subdivided into Hodgkin's disease and low- or high-grade non-Hodgkin's lymphoma (NHL). The principal therapeutic options are polychemotherapy and radiotherapy. Besides the histological classification, staging of the disease with particular regard to risk factors is an essential prerequisite for the therapeutic decision. Diagnostic imaging modalities such as computer tomography, magnetic resonance imaging, and ultrasonography have improved the accuracy of clinical staging such that invasive pathological staging is only necessary in exceptional cases. A novel therapeutic approach is high-dose chemotherapy with autologous haematopoietic stem-cell support. This treatment improves the survival of patients with relapsed high-grade NHL. The place of high-dose therapy as the primary therapeutic option in malignant lymphoma is now being assessed in prospective studies following encouraging results from single-centre studies, including those involving the treatment of low-grade lymphoma. The effects of antibodies directed against lymphatic cells are currently being examined in experimental treatments. An assessment of the viability and rate of proliferation of lymphoma tissue on completion of therapy using sensitive radiological and nuclear medical methods is an important aim for the future. Eingegangen am 5. November 1996 Angenommen am 12. November 1996     

Polymorphism in the promoter region of the apolipoprotein AI gene associated with differences in apolipoprotein AI levels: The European Atherosclerosis Research Study

The effect associated with the substitution of adenine (A) for guanidine (G) in the promoter region of the apolipoprotein AI gene (?75 bp) with plasma apo AI and high-density lipoprotein (HDL) levels was investigated in the European Atherosclerosis Research Study (EARS). This is a study of healthy offspring (cases) of fathers who had suffered premature myocardial infarction (MI) before age 55 years (n = 565) and age- and sex-matched controls (n = 1,078) from 12 European countries, divided into 5 regions based on geography and language. The frequency of the polymorphism was not significantly different among the regions and the relative frequency of the rare A allele was similar in cases and controls (0.159 vs. 0.142) combining data from all regions. Individuals with one or more A allele had significantly higher plasma apo AI levels (P < 0.05) than individuals homozygous for the G allele. This effect was consistent in all regions. The data were analyzed separately in males and females. In females, those with one or more A allele had significantly higher apo AI levels (P = 0.05) than individuals homozygous for the G allele, and this raising effect of the A allele was greater in cases than controls for both apo AI (5.23% vs. 1.56%) and HDL (4.48% vs. 1.89%). In males, the A allele was associated with higher levels of apo AI and HDL, but the effect was much smaller and the differences did not reach statistical significance. In the females, where the effect of the A allele was strongest, the effect on apo AI associated with genotype was evident in non-smokers, and individuals with one or two A alleles had 3.6% higher apo AI and 3.14% higher HDL levels than individuals homozygous for the G allele. However, in the female smokers the raising effect of the A allele was greatly reduced (0.56%). Thus genetic variation in the promoter region of the apo AI gene is associated with differences in apo AI and HDL levels in healthy individuals throughout Europe, but the effect is modulated by gender, environmental factors such as smoking, and a family history of MI.     

Renal regulation of salt balance: a primer for non-purists

The greater than 40-fold range of voluntary salt intake in humans requires corresponding adjustments in renal excretion to maintain balance. Although many mechanisms have been implicated in the regulation of salt output by the kidney, surprisingly little consideration has been given to their quantitative significance and possible interaction. This survey summarizes the effects of changes in glomerular filtration rate, proximal peritubular physical factors, and plasma concentrations of aldosterone and atrial natriuretic factor (ANF), singly and in combination, on the level of salt excretion. Contrary to expectation, even large increases in filtration or decreases in proximal reabsorption have only minor natriuretic effects, due to constancy of fractional reabsorption in downstream nephron segments. Lack of aldosterone release increases salt excretion as much or more than the upstream mechanisms, whereas ANF-induced inhibition of reabsorption in the medullary collccting duct has the largest effect. It may be concluded, therefore, that the potency of these natriuretic factors increases with distance along the nephron, even though each is operating on a progressively small tubular load. However, none of the mechanisms, in isolation, is sufficient to explain salt balance over the range of voluntary intake. Combination of factors demonstrates synergism rather than simple additivity, resulting in more than enough reserve capacity for salt excretion.     

DNA flow cytometry in stage IB and II cervical carcinoma

In a retrospective study the prognostic significance of nuclear DNA content was investigated, as measured by flow cytometry, of the tumor specimens from 212 women with nonpretreated FIGO stage IB and II cervical cancer. One-hundred and thirty cases (62%) were found to be diploid, whereas 82 (38%) were aneuploid. Univariate analysis of the follow-up data showed an increased relative risk (RR) for recurrence free survival (RFS) for stage II tumors (RR = 1.87, 95% CI: 1.13–3.10, P = 0.015) and for age (RR = 1.52, 95% CI: 0.66–3.52 and RR = 2.35, 95% CI: 1.19–4.65, P = 0.032). Ploidy showed a relative risk of 1.33 (95% CI: 0.83–2.13, NS). In addition, univariate analysis of overall survival (OS) revealed similar results. For the subgroup of patients with primary surgery ( n = 151), positive pelvic nodes (RR = 5.38, 95% CI: 2.70–10.71, P = 0.0001) and parametrial extension (RR = 2.53, 95% CI: 1.24–5.17, P = 0.011) were significant factors for OS after univariate analysis, the estimated effects on RFS were slightly smaller. Multivariate analysis of RFS for the whole study population showed age, histologic grade and stage with a slightly increased risk, but no effect was significant. Ploidy with an RR of 0.97 (95% CI: 0.58–1.62) seems to have no influence on prognosis. For the subgroup with primary surgery, ploidy again failed statistical significance with an RR of 1.20 (95% CI: 0.58–2.49). Our results suggest that abnormalities of the nuclear DNA content in this homogeneous group of patients are associated with clinical and morphological prognosticators, however, ploidy is not an independent prognostic factor for RFS, or for the whole study population or for the subgroup with primary surgery.     

Angiogenesis in invasive breast carcinoma: is it associated with parameters of prognostic significance?

Recent experimental and clinical studies suggest that tumour-induced angiogenesis may be an important step in the evolution of malignant tumours, and may be related to prognosis. In our study we examined 42 cases of breast carcinoma (mean age: 56.76 ± 13.5), 21 with lymph node metastases and 21 without. Angiogenesis was evaluated after immunohistochemical staining of tumour vessels, using polyclonal antibody to factor VIII related antigen (VIIIR-Ag) and counting of the three most active areas of neovascularization. In the same manner we counted the microvessels in lymph node metastases. The mean vessel count of node-negative cases (51.16 ± 19.32) did not differ significantly from node-positive cases (45.66 ± 17.44). In contrast patients younger than 50 years had much higher mean vessel counts (54.04 ± 16.47) than did patients older than 70 years (38.03 ± 16.73) producing a P value of ≤0.05. No association was found between tumour size and mean vessel count, nor was there any significant difference between grade I (45.94 ± 16.54), grade II (53.13 ± 23.22) and grade III tumours (51.71 ± 20.64). When we compared the mean vessel count of primary tumours with those of node metastases, we found much lower counts in the latter ( P ≤0.01). The differences in our results from previous studies, probably reflect the heterogeneity which exists between different tumours in their ability to induce angiogenesis. Additionally, there is some evidence in our study that angiogenesis is possibly related to patient age and probably depends on differences in the tumour stroma.     

Measurement of γ-enolase release, a new method for selective quantification of neurotoxicity independently from glial lysis

We have developed a sensitive enzymatic-immunoassay to quantify the level of gamma-enolase (a specific neuronal enzyme) which is released from cultured cells after exposure to various toxins. We show that this method can estimate selectively neuronal cell death without significantly interfering with glial cell death. Indeed, no gamma-enolase is released when glial cells are killed with free-radical producing agents. Experiments comparing the levels of neuronal cell death induced by NMDA or free-radical producing drugs, performed either by measuring gamma-enolase release or using the classical fluorescein diacetate method, yielded similar results. In addition to selectively follow neuronal death in a mixed population of neurons and glial cells, this method provides a way of determining the cell death kinetics from a single culture dish, since enolase can be measured on small samples taken from the culture medium. Finally, we propose these two methods as being complementary and useful neuronal and other cellular death indexes and also to understand the complex problem of glial influence on neuronal survival or death.     

The spectrum of opportunistic filamentous fungi present in the CBS culture collection

The mould collection of the Centraalbureau voor Schimmelcultures, Baarn, The Netherlands, was screened for isolates originating from warm-blooded animals. The range of species indicates that distribution of clinically relevant, pathogenic or opportunistic strains over the fungal kingdom is non-random. Some opportunistic fungi possess adaptations to life under hostile environmental conditions, enabling them to survive inside the human body. Presence of melanin or carotene seems to be an important virulence factor. Opportunistic fungi which sporulate in submersion are able to disseminate or cause severe local mycoses when the aspecific immune system of the host is impaired. Mycoses caused by a few dimorphic fungi, mostly in their natural ecological niche living in association with vertebrates, are promoted by specific immune deficiencies.     

创建良好的心理环境提供全方位优质服务

医院为患者创建温馨、舒畅的心理环境是当前医院改革中亟待解决的极其重要的任务之一。本文从①充分了解患者的心理需求；②注意患者的不良心理因素；③注意医务人员的不良因素三个方面阐述医院如何为患者创造良好心理环境及其重要性。并重点强调自觉培养自身良好的心理素质，保持稳定良好心态及自控力，尊重、理解患者，学习、实践与患者的沟通技巧，增强责任感，树立良好的白衣天使形象等要素是创建的基础。