Mast cells in the labial salivary glands of patients with Sjögren's syndrome: a histochemical, immunohistochemical, and electron microscopical study.

Mast cells in labial salivary glands obtained from patients with xerostomia with or without focal sialadenitis/Sjögren's syndrome were studied. There was no significant correlation between the intensity of local lymphocyte infiltration and the morphometrically analysed number of mast cells staining positive with toluidine blue. Histamine staining with heterologous 11C antiserum showed significantly fewer positive cells than staining with toluidine blue (mean (SD) 62 (10) v 138 (30)). This suggests heterogeneity of the mast cell population. Furthermore, there was a correlation between the focus score and the number of mast cells containing histamine. This suggests that the proliferation of mast cells containing histamine may be locally regulated by the immune inflammation, possibly through mediators from macrophages and fibroblasts. In contrast, the number of mast cells staining positive with toluidine blue could not be used as a marker of the degree of local inflammation. Although transmission electron microscopic analysis did not disclose signs of 'en masse' mast cell degranulation, mast cells may have a role in the local disease process.

Localization of lysozyme mRNA in the labial salivary glands by in situ hybridization in Sjögren's syndrome.

In this study, lysozyme mRNA in labial salivary glands has been localized with in situ hybridization technique using 35S-labeled hen lysozyme cDNA (cDNALZM) as a hybridization probe in normals and in patients with Sjögren's syndrome, 35S-DNALZM:mRNA hybrids were detected only in acinar serous cells, although lysozyme was identified in ductal cells using immunohistochemical techniques. Our results suggest that the serous acinar cells are the only site of lysozyme synthesis in small salivary glands. The presence of lysozyme in ductal cells may be a result of reabsorption from the saliva or concentration from the blood or surrounding tissues.

Herpes simplex virus antigens and inflammatory cells in oral lesions in recurrent erythema multiforme. Immunoperoxidase and autoradiographic studies.

Herpes simplex virus (HSV) antigens were sought in 15 biopsy specimens from both lesional mucosa and clinically healthy looking oral mucosa between attacks in patients with erythema multiforme (EM). Four of the eight biopsy specimens obtained from lesional EM mucosa stained positively with HSV-1-and/or HSV-2-specific antisera applied in direct immunoperoxidase staining. Of the 16 tissue specimens used as controls, two displayed positive staining with HSV-1 and/or HSV-2. Five of the seven biopsy specimens from macroscopically healthy oral mucosa obtained between attacks from patients with recurrent EM stained positively with HSV-1 and/or HSV-2. Of the six tissue specimens used as controls, three stained positively. Most of the local inflammatory mononuclear cells belonged to the T cell series, mainly to the CD-4 subset. A small proportion of the local T cells were blast transformed as assessed by CD-25 expression and [3H]thymidine incorporation. This, together with the findings showing a lower degree of activation in the biopsy from macroscopically healthy looking mucosa between attacks suggest an active role of the cell-mediated immune response in the genesis of oral lesions in EM. The persistence of HSV antigens, and the well-established role of HSV as a precipitating factor in recurrent EM, suggest that HSV may be involved, but since HSV seems to be present in other mucosal lesions as well as in clinically healthy mucosa, quite frequently an additional, hitherto unknown factor must be present in order that EM may occur.

Localisation of lysozyme mRNA in rheumatoid synovial membrane by in situ hybridisation.

Type A synovial lining cells have been shown to contain lysozyme in their lysosomes. This might be phagocytosed because synovial fluid contains lysozyme originating from tissue macrophages and articular cartilage but in arthritides, in particular, from neutrophils. In situ hybridisation with 35S labelled cDNA was used to detect mRNA for lysozyme over synovial lining in patients with rheumatoid arthritis. No hybridisation was found with lactoferrin cDNA, which was used as a negative control. Computer search against the EMBL gene bank (release 14) did not show any significant cross hybridisation to a known sequence. In cytological specimens 35S-cDNA:mRNA hybrids were observed in positive but not in negative control cells. The presence of lysozyme and its mRNA suggests that type A synovial lining cells are of mononuclear phagocyte lineage.

A postmortem study of focal adenitis in salivary and lacrimal glands.

Investigations were carried out on 102 consecutive medicolegal post-mortem subjects to identify signs of focal adenitis in labial, submandibular, and lacrimal glands. There were 19 subjects (18.6%) with focus scores exceeding 1 in one or two of the types of glands. Among the 19, five had had a disease which is generally associated with Sjögren's syndrome or is autoimmune in nature. In another 63 subjects occasional lymphocytic foci were found in one, two, or all three types of gland. Fibrosis, atrophy, and fatty change had occurred most often in the labial salivary glands in those over 50 years of age with or without high focus scores. Fibrosis, atrophy, and fat infiltration had hardly ever occurred in the lacrimal glands, although this is the type of gland in which high focus scores occur most often. The results suggest that there may be a common autoimmune basis for Sjögren's syndrome and other diseases, the mechanisms of which are still incompletely understood. A focus score exceeding 1 may be an indicator of Sjögren's syndrome, but the diagnosis should not be established on the biopsy findings alone.

Fatal intoxication by Remoxipride.

The case history and toxicologic findings of a 23-year-old woman who committed suicide with Remoxipride are described. Remoxipride is a recently developed neuroleptic drug of the benzamide type. Remoxipride was detected in the liver, stomach content, blood, and urine. The concentration of Remoxipride in the blood was 230 mg/L. The recommended therapeutic level for Remoxipride should not exceed 7 to 8 mg/L. The victim had no blood alcohol, but an ethanol concentration of 0.048 g/100 L was detected in the urine. The mechanism of death from Remoxipride intoxication is not known. In clinical studies, sinus bradycardia and infrequent supraventricular and ventricular ectopic beats have been noted.

Oral parameters for the diagnosis of Sjögren's syndrome.

Agreement is probably world wide in the medical profession that patient history is the most relevant part of the patient examination, but at the same time the most demanding part because there is no substitute to lack of knowledge and experience. These form the basis for an often subconscious process of selecting the most important pieces of information to help in decision making. We describe a stepwise forward discriminant analysis with a jackknife-validation in analysis of questionnaires as to diagnosis of Sjögren's syndrome. The second topic of current interest, also due to the need of generally acceptable criteria for diagnosis and classification, is the place of labial salivary gland (LSG) biopsy in such sets of criteria. In the histopathological part of our work we describe findings of a postmortem LSG study from the coroner's office.

Cellular and molecular aspects of inflammation.

Cellular host reaction to noxious agents and damaging events consists of inflammatory, immune and repair responses. These are usually involved in different phases of the host reaction in a well co-ordinated manner, contributing to the well-being of the host. However, when they are excessive, uncontrolled or occur in a vulnerable anatomic location, they can contribute greatly to injury. In general, the effects of the initiating stimulus are much enhanced by secondary involvement of amplification loops, leading to recruitment of nonspecific cells. The number of initially stimulated and/or actively involved cell is, therefore, usually low but of crucial importance for the outcome of the process. As important as understanding of the mechanisms responsible for initiation and amplification of the host response is knowledge of the negative feedback loops responsible for down-regulation of the whole process.

[Malignant diseases as secondary findings in forensic autopsies]. / Maligna sjukdomar som bifynd vid rättsmedicinska obduktioner.

In a study of 228 consecutive medico-legal autopsies, malignant disease was discovered in 19 cases. The malignant diseases are discussed as to their primary sites and histologic types, age groups in which they occurred, conditions with which they may have been associated, symptoms and signs which in some cases may have warned of malignant disease, and supposed reasons why the malignant diseases were not recognized while the deceased were still alive. It was found that undetected malignant diseases occur mainly in the elderly, that chronic renal disease with scarred kidneys and cirrhosis of the liver may be predisposing conditions in cancer development, and that malignant disease in the aged may be undetected because of confusion with general weakness or because of small size and obviously slow growth of the tumor with lack of symptoms.

Surgical technique and operative mortality in coronary artery bypass. A postmortem analysis with castangiography.

Post-mortem analysis with castangiography was performed on 54 patients who died within 30 days of coronary artery bypass surgery. Myocardial failure was the cause of 85% of the deaths. There were 215 coronary anastomoses (4.0 +/- 1.1/patient), 24% of which were non-functioning. Most of the occlusions were due to various technical failures. The most striking features were 1) high occlusion rate (25%) in sequential vein grafts and 2) disastrous complications of coronary endarterectomies. Compared with preoperative angiographic data, only 15 (28%) of the 54 patients were found to have 'complete' revascularization, with patent grafts and all stenosed coronary arteries bypassed. The need for recognition and avoidance of technical complications is stressed: Failures of surgical technique constitute a major risk factor in coronary artery surgery.

Mineral fiber concentration in lung tissue of mesothelioma patients in Finland.

The mineral fibers in lung tissue samples of 19 mesothelioma patients and 15 randomly selected autopsy cases were analyzed using low-temperature ashing, scanning electron microscopy (SEM) and x-ray microanalysis. The fiber concentration ranged from 0.5 to 370 million fibers per gram of dry tissue in the mesothelioma group and from less than 0.01 to 3.2 million fibers per gram of dry tissue in the autopsy group. In 80% of the mesothelioma patients and in 20% of the autopsy cases, the fiber concentration exceeded 1 million fibers per gram of dry tissue. Amphibole asbestos fibers predominated in both groups, and only a few chrysotile fibers were found. In the lungs of six mesothelioma patients, anthophyllite was the main fiber type. The overall analytical precision of sample preparation and fiber counting with SEM was 22%.

Subjective disease experience in Sjögren's syndrome. A computerized discrimination analysis.

A study was made of the ability of a computerized discrimination analysis to distinguish between primary or secondary Sjögren's syndrome on the one hand and, on the other, various rheumatic diseases which may be, but in this study were not, complicated by Sjögren's syndrome. The analysis was based on a questionnaire including 76 two- or three-scale items. Among these 76 questions, five with a maximum potential for distinguishing between various subgroups were selected and obviously represent the questions for the physician to ask when taking the patient's history. As shown by classification matrix tables, computerized analysis of questionnaires might represent a useful way to assess the prevalence of clinical cases of Sjögren's syndrome and to aid health care administrators in assessing the extent of the Sjögren's syndrome problem. In contrast, manual analysis of patients' graded answers did not provide any simple or practicable method for the diagnostic work-up of cases. Therefore it seems that subjective symptoms should not be included in the diagnostic criteria for Sjögren's syndrome, which in clinical work should be based on objective evidence alone.

An immunoperoxidase-autoradiography double labeling method for analysis of lymphocyte activation markers and DNA synthesis.

An immunoperoxidase-autoradiography double labeling method for analysis of lymphocyte activation markers and DNA synthesis is described. For this study expression of MHC locus II coded Ia antigen, interleukin-2 receptor, transferrin receptor and gp 40/80 glycoprotein was analyzed using monoclonal antibodies in avidin-biotin-peroxidase complex staining combined with visualization of [3H]thymidine incorporation by autoradiography. Compared to spontaneous [3H]thymidine incorporation assay information is obtained at single cell level. In contrast to blast indexes calculated from MGG stained preparates, information on the expression of various functional cell surface structures as well as DNA synthesis is also obtained. Double-assay for lymphocyte phenotype and DNA synthesis by flow cytometry might be preferred to light microscopy, but the widespread use of immunoperoxidase staining and autoradiography may make this new kind of approach more easily available. Other advantages worth considering are the possibility of transporting, staining and counterstaining as microscope slides and the permanent nature of the documentation and morphological information obtained. In our experience, this method seems to be useful for studying resting peripheral blood lymphocytes as well as mitogen and antigen induced changes in the lymphocyte activation state.

Lymphocyte activation in oral lichen planus in situ.

The current study evaluated the activation of T-cell mediated cellular immune response in the oral lesions in lichen planus (OLP). Analysis was made of the ultramorphology, lymphocyte activation marker expression, DNA synthesis, and gamma-interferon production of the inflammatory cells in OLP lesions. According to these four different aspects of lymphocyte activation, only a minor fraction, 5% at the most, of all T-cells in situ were activated. This minor fraction, however, not the resting T-cells without these signs of activation, may decide the outcome of the local immune-inflammatory process in OLP. Of the inflammatory cells in situ, however, 81 +/- 5% were Ia positive. This finding may be the result of an Ia inducing capacity of the gamma-interferon produced locally by the activated T-cells.

Determination of cause and mode of death before and after medicolegal autopsy: a comparative study.

Two hundred and twenty-eight consecutive medicolegal autopsies were studied as to the cause of death established by a physician, the mode of death as suggested in the police report, and findings of medical interest often discovered following autopsy. Corrections had to be made even in some cases which seemed to be obvious. With a decrease of the number of autopsies, the records of various registration bureaus would be affected. Autopsies are still necessary for control and correction of clinical causes of death.

Focal adenitis in lacrimal and salivary glands. A post-mortem study.

In the present study the submandibular, labial, and lacrimal glands of 102 postmortem subjects were studied as to the presence of inflammatory foci, fibrosis, atrophy and fatty change. Focal lymphocytic infiltration of these glands with focus scores exceeding 1, one of the findings on which the diagnosis of Sjögren's syndrome is based, was found in 19 cases (18.6%). Fibrosis, atrophy, and fatty change occurred most often in the labial salivary glands of patients over 50 years of age with or without high focus scores. Fibrosis, atrophy and fat infiltration hardly ever occurred in the lacrimal glands although this was the type of gland in which high focus scores occurred most often. The findings suggest that a wider than hitherto recognized spectrum of systemic inflammatory diseases may contribute to lymphocytic adenitis and degeneration of the exocrine glands. The diagnosis of Sjögren's syndrome should be confirmed by additional diagnostic tests.

Xerostomia due to Sjögren's syndrome. Diagnostic criteria, treatment and outlines for a continuous dental care programme and an open trial with Sulfarlem.

The initial evaluation of 25 patients suspected of suffering from Sjögren's syndrome (SS) disclosed that sialopenia and glandular atrophy without focal sialo-adenitis was the second most common cause, after SS itself, of patient complaints. This emphasizes the importance of conclusive diagnostic criteria to prevent overdiagnosis and to form a sound basis for management of xerostomia patients. We found that at the time of diagnostic evaluation, the dental status of our SS patients did not differ from that of the normal Finnish population. This suggests that SS patients can greatly benefit from adequate dental care, assuming that attention is paid to early diagnosis and management. Accordingly, the diagnostic and therapeutic approach needs to be multidisciplinary. We present our current programme for oral and dental care of xerostomia patients and the results of an open trial with Sulfarlem (trithioparamethoxyphenylpropene) which was found not to be the drug of choice in the treatment of dry mouth associated with SS.