The influence of economic interests on alcohol control policy: a case study from Finland.

Finland's participation in the European Union has meant that Finnish markets have been opened to international competition and that the traditional alcohol policy decision-making that revolved around Alko, the state alcohol monopoly company, has become impossible. The influence of private commercial interests increased in the 1990s but not in a straightforward manner. They had their biggest influence in the mid-1990s when the 1994 Alcohol Act was drafted and accepted. After that the influence of commercial interests has declined, and nowadays the alcohol question is again discussed in terms of public health and safety and drinking among young people. Integration did not lead to the expected deregulation of alcohol control but to new forms of regulation, where EU authorities such as the Commission and the EU Court also play an important role. Alcohol policy-making is now more transparent, and free trade and competition without interference are much more stressed than previously. These are the new frames of public intervention in the alcohol question, both in the trade of alcoholic beverages and in the taking care of individuals harmed by the use of alcohol.

Lymphocytic gastritis and Helicobacter pylori infection in gastric lymphoma.

Lymphocytic gastritis and primary gastric lymphoma are rare conditions with unknown aetiology. It has recently been suggested that Helicobacter pylori has a role in the pathogenesis of both of them. The occurrence of lymphocytic gastritis and H pylori was studied in a series of patients with primary gastric lymphoma. The cases of primary gastric lymphomas (n = 35) diagnosed in years 1970-1993 were identified. The specimens of 22 cases contained gastric mucosa sufficiently so that the number of intra-epithelial lymphocytes, severity of gastritis, and occurrence of H pylori could be studied. Lymphocytic gastritis was detected in seven of 22 patients (32%), and in most cases both in antral and body mucosa. Atrophy of the body glands was significantly more severe in lymphocytic gastritis patients. H pylori was detected in 13 of all 22 patients (59%); two of seven lymphocytic gastritis patients (29%), and 11 of 15 (73%) of patients without lymphocytic gastritis were H pylori positive. Patients with gastric lymphoma have significantly increased prevalence of lymphocytic gastritis. Rarity of H pylori in these patients might be connected with atrophic changes in body mucosa. Further studies are needed to show the significance of lymphocytic gastritis as a precursor of gastric lymphoma.

Loss of heterozygosity for chromosome 11 in primary human breast tumors is associated with poor survival after metastasis.

A common feature of the malignant progression of human tumors is loss of heterozygosity (LOH) for various regions of their genomes. Such events encompassing chromosomes 11p15 and 11q23 are frequent in human breast tumors. Here, we have analyzed genetic and clinical characteristics of a series of primary breast tumors in order to determine: (a) a more finely mapped estimate of the involved regions; (b) whether there is a relationship in the presentation of LOH between the two regions; and (c) whether a correlation exists between such LOH and any of the clinical parameters pertaining to each patient. We found that LOH for 11p15.5 and 11q23 occurred in 35 and 46% of the 86 primary breast carcinomas, respectively, but in none of the 10 benign tumors examined. The minimal region of LOH for 11p15 was in the approximately 2-megabase region between loci TH and D11S988. Twenty-nine % of the tumors showed LOH simultaneously at both 11p15 and 11q23, 5% had LOH only at 11p15.5, and 15% had LOH only at 11q23. Among these genetic groups, clinical features such as tumor size, involvement of auxiliary nodes, histological subtype, tumor grade, estrogen/progesterone receptor status, and patient age were not markedly different. However, LOH of 11q23 (either alone or in conjunction with LOH of 11p15) in the primary tumor was found to be highly predictive of aggressive postmetastatic disease course with substantially reduced survival (P = 0.0004; log rank test). We also observed a slight trend toward a more rapid development of metastatic lesions, without obvious site specificity, in patients with primary tumors showing LOH for chromosome 11 in the pathogenesis of human breast cancer; we suggest that its effects are late in the progression of this disease.

[Apoptosis in Hodgkin's disease]. / Apoptose beim Morbus Hodgkin.

Previous studies have concentrated on the proliferative behaviour of the neoplastic cell compartment in Hodgkin's disease (HD). The aim of the current investigation was to analyse the frequency of programmed cell deaths in Hodgkin and Reed-Sternberg (HRS) cells in the different subtypes of HD and to correlate this phenomenon with the expression of the bcl-2 oncogene. For this purpose, we investigated paraffin-embedded material from 63 cases of HD. Oncogene expression was determined by immunohistochemistry with the monoclonal antibody bcl-2-124. The detection of apoptotic cells was facilitated by application of the in situ end-labelling (ISEL) technique. Our results confirmed that bcl-2 expression is low in the lymphocyte-predominant subtype of HD. Apoptotic cells were found in all subtypes to a variable extent and were not significantly associated with any particular subtype. Interestingly, there was no correlation of bcl-2 expression and the presence or absence of apoptotic HRS cells. Hence, other factors must be operative in the regulation of programmed cell death in HD. Such mechanisms have been described for lymphocytes under various conditions, such as negative selection in germinal centres and within the thymus, DNA damage due to irradiation, and cellular cytotoxicity.

Loss of heterozygosity in sporadic human breast carcinoma: a common region between 11q22 and 11q23.3.

The development of sporadic human breast cancer is associated with the accumulation of genetic alterations on several chromosomes. In the case of chromosome 11, loss of heterozygosity (LOH) at loci on the short arm has been well documented and suggests the presence of a suppressor gene(s) at 11p15.5. However, the evidence for similar events on the long arm is less compelling. Here, we determined the prevalence of LOH for chromosome 11q in 44 malignant and 3 benign cases of unselected sporadic breast tumor samples. We found that alteration of chromosome 11q is common in the pathogenesis of breast cancer as 19 of 44 (43%) malignant tumor specimens exhibited LOH. Eleven (58%) of these genetic alterations were specific to the long arm of the chromosome. The smallest region of shared LOH places the target between 11q22 and 11q23.3, the same general region frequently altered in cancers of the ovary, colon, skin, and uterine cervix, perhaps indicating the location of a tumor suppressor gene or genes of importance in each of these different tumor types.

Nonparasitic splenic cysts. Ultrasonographic features and follow-up.

Sixty-three patients with splenic cysts, multiple in 7 cases, were reviewed. Only 3 patients had a history of previous abdominal trauma. The cysts ranged in size from less than 1 cm to 15 cm. They were anechoic in 40 patients, hypoechoic in 16, isoechoic in 4, mixed in one, and in 2 cases the echogenicity could not be assessed due to thick marginal calcifications. The echogenic cysts were larger than the anechoic ones and frequently calcified, and the findings at surgery, fine-needle aspiration biopsy and follow-up suggested the echogenicity to be related to a fresh or previous episode of intracystic hemorrhage. Initially, surgical treatment was undertaken on 10 patients, electively in 9 cases and due to cyst rupture in one. At follow-up (n = 37), the size of the cyst had increased markedly over several years in only 2 patients, necessitating delayed surgery in one. Routine follow-up of asymptomatic splenic cysts was of no clinical value.

Follicular dendritic cells have prognostic relevance in Hodgkin's disease.

The authors' previous study showed the presence of follicular dendritic cell (FDC) networks--though altered--in neoplastic areas, not only in the nodular lymphocyte predominance type, but also in other types of Hodgkin's disease. The present retrospective study was performed on 102 patients to determine whether the presence or absence of FDC networks, or parts of them, in neoplastic areas has prognostic relevance in Hodgkin's disease. Follicular dendritic cells were visualized with the monoclonal antibody Ki-FDC1P, which selectively stains FDCs in paraffin-embedded tissues. Univariate statistical analysis, in which nodular sclerosis (NS) and mixed cellularity (MC) types were combined, showed three prognostically different groups: the best prognosis was associated with nodular lymphocyte predominance cases; the worst with FDC-negative NS or MC cases; and an intermediate prognosis with FDC-positive NS or MC cases. In the NS group, the prognosis of FDC-positive cases was better than that of FDC-negative cases. After multivariate analysis, stepwise modeling identified three prognostic factors at diagnosis: stage (P = .001), FDC status (P = .001), and age (P = .06). The authors conclude that in the most common types of Hodgkin's disease (nodular lymphocyte predominance, NS, and MC), FDC status in the neoplastic area(s) bears prognostic relevance, a positive FDC status predicting a favorable prognosis and a negative FDC status an unfavorable one.

Castleman's disease. Differences in follicular dendritic network in the hyaline vascular and plasma cell variants.

Twenty-seven cases of the hyaline vascular variant and 10 cases of the plasma cell variant of Castleman's disease were studied with the paraffin resistant monoclonal antibodies Ki-FDC1p and/or Ki-M4p against follicular dendritic cells. Studies with the monoclonal antibody Ki-M9, for the detection of sinus lining cells, were also performed on the available frozen tissue in four cases of the hyaline vascular variant. In nine of the 10 plasma cell variant cases, the predominant type of follicular dendritic cell network was similar to that seen in normal or reactive germinal centres. In contrast, the hyaline vascular variant demonstrated either an expanded, disrupted, follicular dendritic cell network (10 cases) or multiple tight collections of follicular dendritic cells (16 cases). Sinus lining cells were not detected in the four cases studied. The difference in the predominant type of dendritic meshwork is an additional distinguishing feature to separate the plasma cell and hyaline vascular variants of Castleman's disease. The patterns of dendritic network seen in the hyaline vascular type, together with the absence of sinus lining cells, appear to favour the hamartoma theory proposed for this variant.

Refinement of regional loss of heterozygosity for chromosome 11p15.5 in human breast tumors.

The familial association of breast cancer with other tumors such as rhabdomyosarcoma that show loss of heterozygosity (LOH) for chromosome 11p15 as well as limited analyses showing LOH for chromosome 11p in breast tumors suggests the presence of a pleiotropic tumor suppressor gene in this region. In order to test this idea, we analyzed DNA samples for 50 matched normal and tumor tissues from unselected breast cancer patients for LOH at loci throughout the chromosome 11p15.5 region. We found that 12.5% of informative cases showed LOH at HRAS1, 26.8% at TH, and 33.3% at both D11S860 and HBB, providing genetic support for this hypothesis. In contrast to previous observations which excluded the involvement of 11p15.5 regions distal to the HBB cluster, our results indicate that the subregion between TH and HBB is a critical region in breast cancer. This region is identical to that identified for the clinically associated tumor, rhabdomyosarcoma, and thus warrants intensive molecular analysis.

Tenascin in reactive lymph nodes and in malignant lymphomas.

Tenascin is an extracellular matrix protein which accumulates in the stroma of various malignant and some benign neoplasms. This has been verified in several immunohistochemical studies. The distribution of tenascin immunoreactivity in lymphatic tissues and neoplasias, however, has not been thoroughly studied. In this investigation we analyzed tenascin immunoreactivity in several benign and malignant lymphatic lesions, including both Hodgkin's and non-Hodgkin's lymphomas. In benign lymph nodes, faint reticular immunoreactivity could be observed in the lymphatic tissue. In benign reactive hyperplasias, a stronger reticular pattern of tenascin immunoreactivity was observed in the interfollicular and medullary areas, while the lymphoid follicles contained only a few positive fibers. A similar immunoreactivity was observed in malignant follicular lymphomas. In diffuse lymphomas, a diffuse meshwork of positively stained fibers was seen. This was also the case for the three cases of Hodgkin's disease of the lymphocyte-predominance nodular subtype. There was no difference in the intensity of the immunoreactivity between benign and malignant disorders. However, in Hodgkin's disease of the nodular sclerosis and lymphocyte-depletion subtypes, a much more pronounced immunoreactivity could be observed in the fibrous septa and the cords. This suggests that the tumor cells are possibly capable of synthesizing growth factors which stimulate fibroblasts to synthesize tenascin. The results indicate that tenascin does not accumulate in the stroma of malignant lymphoid neoplasms with the exclusion of some subtypes of Hodgkin's disease. The distribution of tenascin immunoreactivity in lymphatic tissue is similar to that of the reticular fibers suggesting that the molecules are associated with these structures.(ABSTRACT TRUNCATED AT 250 WORDS)