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)

p53 expression in lymphatic malignancies.

AIMS: To investigate the expression of p53 protein in malignant and benign lymphoid tissues. METHODS: Tissue from 42 non-Hodgkin's lymphomas, 10 Hodgkin's lymphomas, three atypical hyperplasias and five benign reactive hyperplasias was studied immunohistochemically for the expression of p53 protein. RESULTS: Of the 42 non-Hodgkin's lymphomas, 13 (31%) were positive for p53 in some of the tumour cells. In two cases the proportion of positive cells was more than 10% and in four cases it was between 1-5%. These six cases consisted of three Burkitt's lymphomas, one immunoblastic lymphoma, one centroblastic diffuse lymphoma and one angioimmunoblastic lymphoma. In seven cases the proportion of p53 positive tumour cells was less than 1%. These cases comprised three centroblastic diffuse, three centroblastic polymorphic diffuse, and one angioimmunoblastic type lymphoma. In three out of 10 (30%) Hodgkin's lymphomas, a proportion of the Reed-Sternberg cells were p53 positive. One of these was a mixed cellular subtype and two nodular sclerosing subtypes. p53 protein was not expressed in the three atypical hyperplasias or the five benign reactive hyperplasias of the lymph nodes. CONCLUSIONS: The presence of p53 positivity in non-Hodgkin's and Hodgkin's lymphomas indicates that mutations of the p53 gene may play a part in the development of these tumours. The concentration of p53 positivity in high grade lymphomas suggests that p53 is involved in the transformation of low grade lymphomas to more aggressive types. Because no p53 positivity was observed in benign lesions of the lymph nodes, positive p53 immunohistochemical staining in a lymphoid lesion suggests malignancy.

Abnormal CD4:CD8 ratios and delayed germinal center reconstitution in lymph nodes of human graft recipients with graft-versus-host disease (GVHD): an immunohistological study.

We searched for evidence that immunodeficiency in graft-versus-host disease (GVHD) is in part due to alloimmune damage to lymph nodes. We used immunoperoxidase techniques to stain T-cell subsets, pan-B cells, and follicular dendritic reticular cells (FDRC) in frozen sections of lymph nodes from 80 marrow graft recipients (56 with GVHD, 11 autografts, and 13 allografts without GVHD). We found that 46% of the GVHD patients had reversed CD4:CD8 ratios and only 13% of non-GVHD patients had such disturbed ratios (p = 0.006). Pan-B (CD22) cell labeling was present in the follicular regions of 73% of patients without GVHD and only 53% of patients with GVHD (p = 0.05). Focal FDRC staining was geographically concordant with clusters of B cells in 88% of cases (p less than 10(-7)). These data confirm that disturbed intranodal CD4:CD8 ratios are present more frequently in GVHD patients than in non-GVHD patients or in autografted patients. They suggest more delayed follicular B-cell reconstitution in GVHD patients. They show an extremely tight association of FDRC with clusters of B cells in the recovering lymph node, as in the developing fetal node. We hypothesize that the lack of follicular dendritic cells may contribute to dysfunctional B-cell maturation by ablating orderly antigen presentation and clonal expansion in the lymph node cortex.

Influence of Epstein-Barr virus genomes on patient survival in Hodgkin's disease.

In previous studies, Epstein-Barr virus was considered a possible etiologic factor in Hodgkin's disease. Two hundred twenty-nine cases of Hodgkin's disease were investigated for the presence of Epstein-Barr virus DNA using the polymerase chain reaction technique on formalin-fixed, paraffin-embedded lymph node tissue to clarify the clinical importance of the incidence of this genome. In 42 cases (18.3%), genomic DNA was not amplifiable. The remaining 187 cases included the following subtypes: lymphocyte-predominant type (n = 13), nodular sclerosis type (n = 98), mixed cellularity type (n = 68), and lymphocyte-depleted type (n = 8). Sixty-six cases (35.2%) were positive for Epstein-Barr virus DNA. In the statistical analysis of available follow-up data from 130 patients, no influence of a positive Epstein-Barr virus DNA finding on length of survival time was revealed. This was true within the cohort of all patients and within the histologically defined subtypes of Hodgkin's disease. In this investigation, detection of Epstein-Barr virus DNA by polymerase chain reaction showed no prognostic relevance for patients with Hodgkin's disease.

Accumulation of p53 protein correlates with tumour proliferative activity in EBV positive Burkitt's lymphoma.

p53 tumour suppressor gene is often found mutated in Burkitt's lymphoma (BL) cell lines and tumours. We analysed 35 BL tumours for the accumulation of p53 protein, and correlated the results with DNA flow cytometric data on the proliferative activity (SPF), and data on the presence or absence of Epstein-Barr virus (EBV) DNA. More than one-third (37 per cent) of the tumours showed accumulation of p53, which was considered to be consistent with mutation of the p53 gene. Tumours that were positive both for EBV DNA and p53 had significantly higher mean SPF than corresponding EBV DNA negative and/or p53 negative tumours. The proportions of tumour cells with accumulation of p53 appeared to correlate with tumour SPF only in EBV DNA positive BLs. However, there was no apparent association between accumulation of p53 and the presence or absence of EBV DNA. These findings are suggestive of multiple pathways in BL tumour progression.

Abdominal ultrasonography in myelofibrosis.

The findings at abdominal ultrasonography (US) in 40 patients with myelofibrosis were reviewed, 20 patients being examined at initial diagnosis and 31 at later stages. Splenomegaly was found in 80% at initial diagnosis and in 97% at later stages. The spleen of 2 patients appeared homogeneously hypoechoic and inhomogeneous in one. Focal splenic lesions were seen in 5, and calcifications in 6. Mixed splenic lesions proved to be metastases in one and hyperechoic lesions in another patient were due to extramedullary hematopoiesis. Hepatomegaly was found in 25% at primary diagnosis and in 39% at later stages. Focal hepatic lesions were seen in 7 patients, and proved to be metastases in 3. The focal lesions in 2 of these patients were extramedullary hematopoiesis, which was hypoechoic in one and hyperechoic in the other. Ascites was seen in 4 patients and lymphadenopathy in one. US could not reliably differentiate between extramedullary hematopoiesis and malignancy. Fine-needle biopsy may be performed for definitive diagnosis.

[Influence of Epstein-Barr virus genome on patient survival in Hodgkin's disease]. / Einfluss von Epstein-Barr Virusgenom auf die Uberlebenszeit von Patienten mit M. Hodgkin.

In the literature EBV is considered a possible etiologic factor for Hodgkin's disease (HD). We investigated 187 cases of HD for the presence of Epstein Barr virus using the polymerase chain reaction (PCR) technique on formalin fixed, paraffin embedded lymph node tissue to clarify the clinical importance of the incidence of this genome. The 187 cases included all subtypes. 66 cases (35.2%) were positive for EBV DNA. The statistical analysis of follow-up data from 130 patients revealed no influence of EBV DNA on survival time. In our investigation detection of EBV DNA by PCR showed no prognostic relevance for patients with HD.

Effect of biliary tract procedures on duodenogastric reflux and the gastric mucosa.

The effect of alterations in the biliary tract on the gastric milieu was evaluated in gallstone disease and after cholecystectomy or biliary fenestration and compared with a control group. Endoscopic bile reflux was often found in gallstone patients (67%) and almost always after cholecystectomy (89%). Gastric bile acid concentrations were greater in the gallstone patients than in the control patients, were higher still after cholecystectomy, and were highest after biliary fenestration. The pH of the gastric fluid was more alkaline in the cholecystectomized groups. Lysolecithin concentrations were generally low and did not differ between the groups, nor was there any difference in scintigraphic reflux between the groups. Endoscopic erythematous gastritis correlated with the grade of bile reflux and was a common finding after biliary tract procedures. There were no consistent histologic findings associated with duodenogastric reflux. Helicobacter pylori colonization rates were similar in the various patient groups and were not affected by the reflux grade.

Ultrasonography of spleen and liver in staging Hodgkin's disease.

Ultrasound (US) findings and accuracy in detecting splenic and hepatic involvement were analysed in 137 unselected, untreated patients with Hodgkin's disease. Histology was available from the spleens of 61 patients and the livers of 59 patients. In 20 patients the spleen appeared abnormal at US; containing focal hypoechoic lesions in 14, being enlarged in 13 and inhomogeneous in 2 patients. Most focal lesions were less than 10 mm. The sensitivity of US in detecting involvement of the spleen was 54% and the specificity 100%; the ability of US to detect hypoechoic splenic lesions improved during the study period. Focal hypoechoic hepatic lesions were found in three patients; histological examination of these showed benign changes in one and suspicious finding in the second. In the third the lesion disappeared during chemotherapy. In three cases with definitive histological evidence of liver involvement, US results were false-negative. The results indicate a higher diagnostic efficacy for US in the detection of splenic than hepatic involvement by Hodgkin's disease.

Follicular dendritic cells in Hodgkin's disease.

The distribution of follicular dendritic cells (FDCs) was studied in 66 lymph nodes affected by Hodgkin's disease (HD) from as many patients with the use of the monoclonal antibody Ki-FDC1P, which stains FDCs in paraffin sections. Two distinct FDC patterns were distinguishable in the neoplastic areas: pattern A, showing FDC networks occupied by nongerminal center cells, often expanded and disrupted; and pattern B, with FDCs rare or lacking. Pattern A, with follicle-occupying cells represented by epithelioid and lymphocytic and histiocytic (L and H) cells, was found in about 90% of the cases of nodular lymphocyte predominance type and in about half of the cases of nodular sclerosis type, with the follicle-occupying cells being lacunar cells. In the group of mixed cellularity type, approximately one-fifth of the cases exhibited pattern A and in these cases the follicle-occupying cells were Sternberg-Reed, Hodgkin's, and epithelioid cells. The presence of follicular structures, although abnormal, is a more common occurrence in HD than is appreciable with the use of conventional histologic methods.

A malignant Leydig cell tumour associated with testicular trauma and prostatic carcinoma.

A case of metastatic Leydig cell carcinoma without sex hormone overproduction is reported. The patient had had a prior testicular contusion trauma on the same side after which the testicle had been swollen and firm. The possible aetiological role of extreme trauma is discussed. Radical orchidectomy is recommended for large tumours because of the difficulty in predicting malignant potential, and routine follow-up with retroperitoneal ultrasound scanning for 10 years in all cases.