Histiocytic necrotizing lymphadenitis without granulocytic infiltration

Summary Twenty-seven cases of an unusual necrotizing lymphadenitis previously described only in Japan are reported as occurring in West Germany (23 cases), Iran (1 case), Italy (1 case), Korea (1 case) and Spain (1 case). The lesion frequently develops in the cervical lymph nodes of young women. It is characterized by infiltration of the cortex and/or paracortex by large collections of proliferating histiocytes and is devoid of granulocytes. Complete or, more often, incomplete necrosis of lymphoid tissue is seen in all cases. In cases with incomplete necrosis, the histiocytes are interspersed with pyknotic cells and nuclear debris. Based on the histological findings, the term histiocytic necrotizing lymphadenitis without granulocytic infiltration is proposed. Lesions to be considered in a differential diagnosis are malignant histiocytic neoplasms and necrotizing lymphadenitis with granulocytic infiltration, which is seen in lupus erythematosus and bacterial infections. The aetiology of histiocytic necrotizing lymphadenitis without granulocytic infiltration is still unclear. Some clinical and histological features indicate the possibility of an underlying viral infection.This study was supported by the Kind-Philipp-Stiftung     

Performance of an IS6110-based PCR assay and the COBAS AMPLICOR MTB PCR system for detection of Mycobacterium tuberculosis complex DNA in human lymph node samples

We compared the performance of two PCR assays, an IS6110-based in-house protocol and the COBAS AMPLICOR MTB PCR (COBAS MTB) system, for the detection of Mycobacterium tuberculosis complex in 43 human lymph node samples from 40 patients. For the in-house PCR and the COBAS MTB assays, respectively, sensitivities were 87.5% versus 45.5% (P < 0.05), specificities were 100.0% versus 91.3% (P > 0.05), and inhibition rates were 4.8% versus 19.5% (P < 0.05). For the COBAS MTB system, additional N-acetyl-L-cysteine-NaOH pretreatment of the samples changed neither the inhibition rate nor the sensitivity significantly.     

Blood coagulation and fibrinolysis after long-duration treadmill exercise controlled by individual anaerobic threshold

For rehabilitation training it is recommended that the intensity of exercise should be clearly below the individual anaerobic threshold (IAT). We investigated blood coagulation, particularly endogenous thrombin potential (ETP) and fibrinolysis following a standardized treadmill (TR) ergometer test at 90% IAT for 60–120 min. Sixteen healthy male non-smokers underwent the TR test. Blood samples were taken after a 30-min rest, immediately after exercise, and 2 h after exercise completion. Extrinsic and intrinsic total (TTP_ex+in) and endogenous (ETP_ex+in) thrombin potential, prothrombin fragment 1+2 (F1+2), thrombin-antithrombin complex (TAT), plasmin-2-antiplasmin complex (PAP), D-dimer, tissue plasminogen activator antigen and activity (tPA-AG and tPA-ACT) and plasminogen activator inhibitor type 1 antigen and activity (PAI-1-AG and PAI-1-ACT) were measured. Immediately after TR, F1+2, TAT and TTP_ex+in were increased (P<0.05) while ETP_ex+in remained unchanged. In contrast, PAP, D-dimer, tPA-AG, tPA-ACT (P<0.05) were distinctly enhanced while PAI-1-ACT was decreased (P<0.05) immediately after exercise. The changes in tPA-AG, tPA-ACT, and PAI-1-ACT were reversed to nearly baseline while the enhancement in PAP and D-dimer was prolonged by more than 2 h after exercise. Long-duration exercise between 60 and 120 min controlled by IAT (90%) on a TR ergometer only implicates a small increase in thrombin generation markers and total (free and ₂-macroglubulin-bound thrombin), but not in endogenous (free) thrombin potential alone. In contrast, fibrinolysis is distinctly increased after this type of exercise. Endurance exercise with an intensity below 90% IAT and a duration below 2 h generates a more favourable condition for fibrinolysis than for blood coagulation in healthy young subjects. Data are given as mean (SD).     

Ultrastructural changes in hepatocytes of precision-cut rat liver slices after incubation for 24 and 48 hours

Hepatocytes of precision-cut rat liver slices were studied by means of transmission electron microscopy after long-term incubation (24–48 h) in comparison with freshly prepared slices, indicating reversible and irreversible intracellular alterations of the cells. After 24 h incubation the morphological image in transversal sections of slices is characterised by a central zone of damaged and necrotic cells flanked by two to several superficial layers of viable cells. This is typical of a diffusion gradient of oxygen tension and nutrient content from the surface to the centre of the slices. In adapted cells on the surface of the slices we observed an organelle-free layer of fine granular material in the apical cytoplasm followed by parallel oriented stacks of rough endoplasmic reticulum near by. Mitochondria of essentially normal appearance in adapted cells did not contain flocculent densities, which were observed in damaged cells only. The cytoplasm of parenchymal cells consisted of defined areas of clear cytoplasmic material containing numerous branching tubular profiles of smooth endoplasmic reticulum, presumably in the regions with depleted glycogen aggregates. Subcellular signs of necrosis are destroyed mitochondria, dilated endoplasmic reticulum free of ribosomes and clumping of chromatin in the nucleus of hepatocytes. No appreciable differences of the cell organelles were observed between 24 and 48 h of incubation, but the incidence and intensity of signs of necrosis increased with the duration of incubation and the thickness of the slices. The process of these changes may reflect the phenomenon of cellular adaptation and of hypoxic cellular injury in the periphery and the centre of the slices, respectively.     

Reduced dermal infiltration of cytokine-expressing inflammatory cells in atopic dermatitis after short-term topical tacrolimus treatment

BACKGROUND: In several clinical studies, topical calcineurin inhibitors have been shown to be effective in the treatment of atopic dermatitis (AD). They target signaling pathways that control gene expression, particularly the expression of cytokines. OBJECTIVE: We examined the cellular infiltrate in skin lesions of 10 patients with AD and characterized the cytokine pattern expressed by the infiltrating cells before and after short-term topical therapy with tacrolimus 1% ointment. METHODS: Skin biopsies were examined for histologic alterations (hematoxylin and eosin staining), composition of the cellular inflammatory infiltrate (immunofluorescence), and cytokine expression (ribonuclease protection assay, ELISA, immunofluorescence) before as well as 1 and 3 weeks after initiation of tacrolimus therapy. For comparison, biopsies from nonlesional AD and normal skin were analyzed. Systemic immunologic effects were assessed by analyzing peripheral blood leukocytes (immunofluorescence) as well as in vitro stimulated pan-T-cell cytokine production (ELISA). RESULTS: All patients showed a significant improvement of their skin lesions associated with a marked regression of spongiosis, acanthosis, and density of the cellular infiltrate in the dermis. The last was a result of reduced infiltration of T cells, B cells, and eosinophils. In contrast, the numbers of mast cells did not change. Moreover, the expression of the T H 2 cytokines IL-5, IL-10, and IL-13 in CD4 + T cells was reduced after therapy. Interestingly, tacrolimus therapy was also associated with a reduction of CD8 + T cells expressing the T H 1 cytokine IFN-gamma. Furthermore, the numbers of epidermal CD1a + dendritic cells increased after treatment. In the peripheral blood, a decrease of granulocytes (eosinophils and neutrophils) but no changes in the distribution of lymphocyte subpopulations were noticed. CONCLUSION: Topical tacrolimus treatment has anti-inflammatory effects on AD skin as indicated by reduced infiltration of cytokine expressing inflammatory cells. No evidence for drug-induced systemic immunosuppression was obtained.     

Anaphylaxis to wheat beer.

BACKGROUND: Despite its worldwide and abundant consumption, beer has rarely been found to cause anaphylaxis. Barley malt contained in lager beers seems to be an important elicitor. OBJECTIVE: To report the unusual case of severe anaphylaxis following the ingestion of wheat beer. METHODS: A 59-year-old man experienced angioedema, generalized urticaria, and unconsciousness after ingestion of wheat beer. He tolerated lager beer well. For diagnostic evaluation, skin prick tests, oral challenge tests, and identification of specific IgE antibodies were performed. RESULTS: Skin prick test results with standard series of common aeroallergens and food allergens were negative with the exception of a 1 + reaction to wheat flour. The results of skin prick tests with native materials were positive for 2 brands of wheat beer and wheat malt shred but negative for baker's yeast, hops, and a brand of lager beer. Oral challenges with wheat beer or wheat flour elicited urticaria. By CAP-FEIA, specific IgE antibodies to wheat and barley flour but not to hops or baker's yeast were found in serum. Immunoblot analysis revealed that patient's IgE was bound to a protein of approximately 35 kDa in wheat extract. CONCLUSIONS: This is the first report, to our knowledge, on anaphylaxis to beer attributable to wheat allergy.     

Fas and Fas-ligand are expressed in the uteroplacental unit of first-trimester pregnancy

PROBLEM: Fas and Fas-ligand (FasL) are thought to provide a strategy for reducing graft rejection in immunologically 'privileged' tissues by controlling injurious lymphocyte reactions. As the uteroplacental unit is often defined as an immune-privileged site, we investigated the expression of Fas and FasL in this tissue in the first trimester of pregnancy. METHOD OF STUDY: Western blotting, immunohistochemistry, and double immunofluorescence were used for this examination. RESULTS: Western blotting with purified first-trimester trophoblast cells revealed one specific band for FasL. The presence of FasL on different trophoblast populations could be confirmed by immunohistochemistry and double immunofluorescence. In the villous part of the placenta, FasL is mostly located on cytotrophoblast cells with no access to maternal blood flow, whereas in trophoblast-invaded uterine tissue, interstitial trophoblast cells, which are in close contact with maternal leukocytes, revealed a strong signal for FasL, but no staining for Fas on these cells. However, Fas was found on CD45+ maternal leukocytes. CONCLUSION: Based on our experimental findings, we speculate that the abundant presence of FasL on trophoblast cells within the maternal decidua may play an important role in the maintenance of immune privilege in the pregnant uterus by endowing fetal trophoblast cells with a defense mechanism against activated maternal leukocytes, whereas in the villous part of the placenta, the Fas FasL system seems to be involved in the regulation of placental growth.     

Gestational diabetes mellitus

Gestational diabetes (GDM) is defined as any degree of glucose intolerance with onset or first recognition during pregnancy and is associated with increased feto-maternal morbidity as well as long-term complications in mothers and offspring. GDM is diagnosed by an oral glucose tolerance test (OGTT) or fasting glucose concentrations in the diabetic range. In case of a high risk for GDM/type 2 diabetes (history of GDM or prediabetes [impaired fasting glucose or impaired glucose tolerance]; malformation, stillbirth, successive abortions or birth-weight > 4500 g in previous pregnancies) performance of the OGTT (120 min; 75 g glucose) is recommended already in the first trimester and--if normal--the OGTT should be repeated in the second/third trimester. In case of clinical symptoms of diabetes (glucosuria, macrosomia) the test has to be performed immediately. All other women should undergo a diagnostic test between 24 and 28 gestational weeks. If fasting plasma glucose exceeds 95 mg/dl, 1 h 180 mg/dl and 2 hrs 155 mg/dl after glucose loading (OGTT) the woman is classified as GDM (one pathological value is sufficient). In this case a strict metabolic control is mandatory. All women should receive nutritional counseling and be instructed in blood glucose self-monitoring. If blood glucose levels cannot be maintained in the normal range (fasting < 95 mg/dl and 1 h after meals < 130 mg/dl) insulin therapy should be initiated. Maternal and fetal monitoring is required in order to minimize maternal and fetal/neonatal morbidity and perinatal mortality. After delivery all women with GDM have to be reevaluated as to their glucose tolerance by a 75 g OGTT (WHO criteria).