Triggering receptor expressed on myeloid cells 1 and 2 in patients with chronic maxillary sinusitis.

PURPOSE: Chronic sinusitis can result from variable types of immune-mediated process, whose pathogenesis is not fully understood. Triggering receptors expressed on myeloid cells 1 and 2 (TREM-1, TREM-2) are involved in myeloid cell activation enabling these cells to fine-tune the inflammatory response, which may have an impact on subsequent adaptive immunity and may be the key factor in pathogenesis. The aim of the study was to analyse soluble TREM-1 and TREM-2 molecules in maxillary sinus lavage fluid and compare the defined subgroups selected from patients with chronic sinusitis with/without nasal polyps and allergy (asthma and allergic rhinitis). METHODS: The levels of soluble TREM-1 and TREM-2 were measured by Elisa test in a cohort of patients with chronic maxillary sinusitis (n=45). We compared subgroups of patients with nasal polyps (n=33) and allergy (n=25: inclusive of asthma (n=11) and allergic rhinitis (n=14)) with the control group of patients without nasal polyps (n=13), and without allergy (n=21). RESULTS: The study did not prove the difference between subgroups with and without nasal polyps. The levels of soluble TREM-1 did not differ significantly between patients with allergy (asthma and allergic rhinitis) and the control group without allergy (p=0.4804). The levels of soluble TREM-2 were significantly higher in patients with allergy (p=0.0028), asthma (p=0.0103) and allergic rhinitis (p=0.0137) as compared with the control group. CONCLUSION: Our results suggest the role of TREM-2­mediated activation of myeloid cells in chronic sinusitis accompanied by allergy, asthma, and allergic rhinitis (Tab. 6, Ref. 25).

A follow-up survey of patients with acquired angioedema due to C1-inhibitor deficiency.

BACKGROUND: Acquired angioedema due to C1-inhibitor deficiency (C1-INH-AAE) is a rare form of bradykinin-mediated angioedema. It is diagnosed by complement testing; its treatment consists of the management of angioedema (AE) attacks and of underlying disease. OBJECTIVE: Evaluate the results of the clinical follow-up of patients with C1-INH-AAE. METHODS: Between 1999 and 2020, 3938 patients with angioedema were evaluated, and 17 diagnosed with acquired C1-INH deficiency were followed-up. RESULTS: Mean age of the 17 patients was 61 years at diagnosis. In 33%, ACE inhibitors provoked AE attacks. Autoantibodies against C1-INH were detected in 10 patients at diagnosis and in a further patient during follow-up. The AE attacks involved the skin in 70.6%, the upper airways in 41.2% and the tongue/lip in 52.9% of patients. Twelve of the 17 patients had an underlying condition, mainly (n = 11) lymphoproliferative disease. In 10 patients diagnosed with a haematological disorder, AAE symptoms preceded the onset of the latter. One patient has not experienced an AE attack since diagnosis. Twelve patients were treated for angioedema attacks, and 32% of the attacks required acute treatment. PdC1-INH was used to relieve AE attacks, and rituximab for the treatment of underlying disease (in six patients). Six patients had multiple AE attacks before any treatment. The symptom-free period increased in five patients after the on-demand administration of pdC1-INH concentrate and following treatment of the underlying disease in two patients. CONCLUSION: Early diagnosis of C1-INH-AAE and underlying disease is indispensable to reduce disease burden by introducing appropriate, individualized treatment and regular follow-up.

Continuous and long term measurement of reticuloruminal pH in crossbreed dairy cows in Brazil by an indwelling and wireless data transmitting unit / Medidas contínuas e de longo prazo do pH retículo-ruminal em vacas leiteiras brasileiras por meio de uma unidade interna de transmissão de dados sem fio

O objetivo do presente experimento foi medir continuamente valores de pH e temperatura em vacas leiteiras usando uma unidade interna de transmissão de dados sem fio. Valores de pH retículo-ruminais foram medidos automaticamente a cada 600 segundos por um período de 50 dias em três vacas leiteiras Holandesas, no pós-parto recente. Valores de pH retículo-ruminais médios diferiram (P<0,05) entre as três vacas (5,69±0,20; 6,10±0,18; 5,99±0,15), assim como o tempo em minutos por dia (332; 23; 18) mantido abaixo de pH 5,5. A variação diurna de pH nas vacas 2 e 3 demonstrou um padrão circadiano e frequente, como consequência dos momentos de fornecimento da alimentação e da ingestão alimentar, respectivamente. Esse padrão diário não pode ser observado no padrão de pH da vaca 1. Os picos e os valores baixos de pH na vaca 1 eram aleatórios, sem relação evidente com os momentos de alimentação, e as amplitudes de pH eram igualmente desordenadas. O valor de pH retículo-ruminal permaneceu anormalmente baixo nesta vaca durante todo o período de observação, caracterizando uma acidose ruminal subaguda. A temperatura retículo-ruminal da vaca 1 foi mais baixa (38.8°C; 39.1°C; 39.0°C) e ela bebeu mais frequentemente por dia (9,5; 6,4; 7,0) quando comparada com as vacas 2 e 3 (P<0,05). O exame clínico revelou um deslocamento de abomaso à esquerda (DAE). Pela literatura consultada, este é o primeiro relato indicando um padrão de pH e temperatura em uma vaca com DAE.(AU)

Prevalence of DFNB1 mutations among cochlear implant users in Slovakia and its clinical implications.

Hereditary etiology plays an important role in bilateral profound deafness as a main indication for cochlear implantation. Mutations in DFNB1 locus account for most of the inherited deafness cases in Caucasians. To provide actual data on mutation prevalence among implanted deaf subpopulation, we performed DNA analysis of GJB2 and GJB6 genes in 131 unrelated Slovak cochlear implant users. Eight previously described causal mutations and one probably pathogenic missense variant (c.127G>A) were detected in the GJB2 gene in 58 (44.28%) subjects. The most common mutation found was c.35delG with frequency 83.02% of all disease alleles, followed by c.71G>A, c.1-3201G>A, c.313_326del14, c.109G>A, 167delT, c.269T>C, and c.333_334delAA. GJB6 deletion delD13S1830 was identified in only one subject, in double heterozygosity with a GJB6 mutation. Thus, the deafness cause could be clearly attributable to DFNB1 mutations in 36.64% of the patients examined. In summary, the mutation profile found in our cohort was similar to the mutation spectrum reported for Central European deaf populations. The mutation prevalence in cochlear implant users was, however, almost by 25% higher than previously established for non-implanted hearing-impaired population in Slovakia. Finally, we also demonstrate a certain variability in deafness onset in patients with causal genotype and coincidence with other risk factors for deafness. Our results underline the importance of genetic tests in all cochlear implant candidates.

Sex hormones in hereditary angioneurotic oedema.

OBJECTIVE: The fluctuations in sex hormone levels at the beginning of adolescence, in the perimenopausal period, during pregnancy or during the use of oral contraceptives can precipitate oedematous attacks in hereditary angioneurotic oedema (HANO). Attacks usually disappear after the onset of menopause. This study was undertaken to establish any relationship between the serum levels of sex hormones and the incidence of HANO attacks. PATIENTS AND MEASUREMENTS: Serum levels of LH, FSH, progesterone, oestradiol, testosterone, PRL and SHBG were measured in 78 patients [mean age 30.3 years (range 4-70 years)] with HANO. A questionnaire was used to explore the medical history of adult patients to characterize the evolution and the characteristics of attacks. RESULTS: The number of attacks was significantly higher [odds ratio (OR) 6.36 (1.31-30.81); P = 0.022] in females with high progesterone levels (> or = 4 nmol/l), irrespective of age, menstrual cycle and danazol dose. The OR was even higher [13.4 (2.2-81.4); P = 0.005] when only subcutaneous attacks were considered. Multiple logistic regression analysis demonstrated a significantly lower attack frequency during 1-year follow-up in patients with a higher (40 nmol/l) SHBG level (OR 0.25 (0.07-0.90); P = 0.034). This difference existed independently of age and danazol dose. CONCLUSION: In view of these results, the monitoring of progesterone and SHBG levels can prove useful in the prediction of attacks in hereditary angioneurotic oedema.

Amelioration of murine colitis by feeding a solution of lysed Escherichia coli.

BACKGROUND: Immune reactivity towards the bacterial intestinal flora plays an important part in the pathogenesis of inflammatory bowel disease. Disease activity can be positively influenced by the administration of living probiotic bacteria. We investigated the effect of soluble bacterial antigens extracted from Escherichia coli (strain Laves) on the disease activity of murine colitis. METHODS: C3H.IL-10-/- and BALB/c mice with dextran sulphate sodium-induced colitis were treated with either a bacterial lysate from E. coli or with a placebo. Mice were monitored and inflammation was assessed by histological scoring, analysis of fecal IL-1beta and measurement of cytokine production by ELISA. T cell proliferation was quantified by 3H-thymidine incorporation. RESULTS: Clinically and histologically, bacterial-lysate-treated mice revealed significantly (P < 0.05) fewer signs of colitis than placebo-treated mice. Fecal IL-1beta and mucosal TNF-alpha and IFN-gamma concentrations were significantly lower (P < 0.05) in verum-treated mice than in the placebo group. Furthermore, lymphocyte proliferation after stimulation with lipopolysaccharide or caecal bacterial antigen was significantly (P < 0.05) reduced in verum-treated mice. CONCLUSION: The use of E. coli lysate is effective in the amelioration of murine colitis. This effect may be due to a decreased Th1 reaction and to an induction of tolerance against bacterial antigens.

Does intravenous ondansetron affect gastric emptying of a solid meal, gastric electrical activity or blood hormone levels in healthy volunteers?

BACKGROUND: In previous studies, tropisetron has been shown to accelerate gastric emptying of a solid meal. However, it is uncertain whether other specific 5-hydroxytryptamine-3 receptor antagonists, such as ondansetron, also have a gastroprokinetic effect in humans. AIM: To evaluate the effect of ondansetron on gastric half-emptying time (T1/2) of a solid meal, gastric myoelectrical activity and hormone levels in 14 healthy volunteers. METHODS: In a placebo-controlled, randomized, crossover study, we investigated the effects of ondansetron (8 mg intravenously) on the gastric emptying of solids (by scintigraphy), gastric myoelectrical activity (by electrogastrography) and the post-prandial release of cholecystokinin, gastrin, human pancreatic polypeptide, gastric inhibitory polypeptide, vasoactive intestinal polypeptide, motilin, substance P and galanin. RESULTS: The average T1/2 values were 86 min and 85.5 min without lag time (P=0.082) and 92 min and 93 min with lag time (P=0.158) for the placebo and ondansetron treatments, respectively. The average T1/2 of female volunteers was significantly longer than that of male volunteers. The dominant gastric electrical frequency and hormone plasma concentrations were not altered by ondansetron. CONCLUSIONS: Ondansetron did not affect the gastric emptying of solids, the dominant gastric electrical frequency or the plasma concentrations of the analysed gastrointestinal peptides.

Angiooedema due to acquired deficiency of C1-esterase inhibitor associated with leucocytoclastic vasculitis.

A hereditary and an acquired type of C1-esterase inhibitor deficiency have been described. Manifestations characteristic of both forms include recurrent subcutaneous and submucosal angiooedema. Acquired C1-esterase inhibitor deficiency has been observed in association with lymphoproliferative disorders, malignancy, autoimmune diseases and infections. We report on a case with the acquired form of the disease accompanied by leucocytoclastic vasculitis. Treatment with antimalarial agents resulted in complete resolution of symptoms and signs. Furthermore, C1-esterase inhibitor concentration and activity, as well as C1 levels, all returned to normal.

Some aspects of complementarity in the immune system. A bird's eye view.

The burden of this paper is the suggestion that the defence capacity of the immune system is rather limited. It cannot stand in readiness to deal with a practically endless diversity and abundance of microbes. In contrast to conventional thinking the current model proposes: (1) The core idea that cells of the immune system are basically and constantly interconnected with host cells (e.g., through TCR-MHC interactions) and that foreign antigens (peptides) may tend to obstruct such interactions. Peptides presented during a viral infection typically decrease complementarity between the structures that are the products of the major histocompatibility complex (MHC) genes (or other genes related to it) and T cells. The altered MHC profile exposes infected cells to a polyclonal immune attack from other T cells such that tissue destruction occurs in an allograft rejection-like fashion. This may explain why a substantial portion of T cell numbers is activated when only a small number of specific T cells is 'obstructed' from functioning by the presence of nonself peptides. (2) Phagocytes 'see' targets even in a non-immune host because complement distribution associated with polyreactive natural antibodies magnifies sensitization differences between pathogens and host cells. (3) There is only a probability that hypermutation will successfully change the genome in some B cell clones to produce high affinity antibodies that prevent the re-infection of the host by the same pathogen, but cannot conquer primary infections. (4) The history of the development of the immune responses suggests that during prolonged interaction between host and microbes in our natural habitat, carried on over many generations, the adaptive antibody population may facilitate the evolution of the natural antibody repertoire. The model predicts that microbes, which are not a part of the local environment, may invade the organism without significant resistance. The model is discussed in various interactions for survival in the context of infection and tumorigenicity.

[HLA genomic tissue typing in myasthenic patients with rheumatoid arthritis]. / A humán leukocytaantigének molekuláris genetikai vizsgálata myastheniás elózmény után kialakult rheumatoid arthritisben.

In a 36 years old male and a 56 years old female myasthenic patient thymectomy was performed several years ago. In the male patient 5, and in the female patient 7 years after the operation rheumatoid arthritis developed. The rheumatoid arthritis in the male patient was seropositive with marginal erosions in the carpometacarpal and in the tarsometatarsal joints. The female patient had no joint destruction and was seronegative as well. The female patient had also an abnormal ratio between the separated CD4 and CD8 T-cells. The major histocompatibility complex determined by the serological methods revealed a haplotype of HLA-A1-B8-D3-DQ2, which is typically due to the myasthenic disease. In the female patient the molecular analysis of the HLA-D region showed a HLA-DRB1* 0401 allele, which is frequently associated with rheumatoid arthritis. The male patient had no allelic variant which could be related to his chronic disabilitating joint disease.

C5b-9 and interleukin-6 in chronic hepatitis C. Surrogate markers predicting short-term response to interferon alpha-2b.

BACKGROUND: Available data and our observations suggest that elevated levels of interleukin (IL)-6 and -10 and some complement parameters may be associated with a poor response to IFN alpha. We evaluated how baseline levels of C5b-9, IL-6, and IL-10 influence the outcome of IFN alpha treatment. METHODS: Fifty-one patients with established chronic hepatitis C were enrolled and treated with IFN alpha-2b. Before and after a 12-week-IFN-treatment (3 MU or 5 MU tiw) serum levels of IL-6, IL-10, C5b-9 and RNA of hepatitis C virus (HCV) were assessed. Sera of 46 sex- and age-matched, healthy blood donors served as control. RESULTS: While two-thirds of patients was considered 'responder', 14 patients had no significant decrease either in HCV RNA or in ALT levels. In the responder's group lower baseline levels of IL-6 and C5b-9 were found than those in the 'non-responder' group. As a result of IFN therapy HCV RNA and C5b-9 levels significantly decreased. While the serum concentration of IL-6 increased during the follow-up period, regarding IL-10, no change was observed. In patients with 'low' baseline levels of C5b-9 (<2053 ng/ml) IFN alpha resulted in a significantly (P = 0.0005) higher decrease in HCV RNA level. Regarding 'low' IL-6 values (< 1.47 pg/ml) similar but somewhat less significant (P = 0.0039) difference was found if the change of HCV RNA was investigated. The odds ratio of patients with low IL-6 and/or C5b-9 to responding to IFN alpha treatment was almost 10 times (CI: 9.1 (1.8-50.9)) higher as compared with patients without 'low' levels of these parameters. CONCLUSION: Our data suggest that serum level(s) of IL-6 and/or C5b-9 taken prior to the initiation of IFN treatment may serve as surrogate marker(s) in evaluating patients with chronic hepatitis C whether to get IFN alpha in monotherapy or to consider having combination therapy in the form of IFN alpha-ribavirin.

Changes in the acute phase complement component and IL-6 levels in patients with chronic hepatitis C receiving interferon alpha-2b.

In order to study the effect of interferon alpha on the levels of acute phase complement proteins in vivo, serum concentrations of C9 and C1-inhibitor (C1-INH) were measured in patients with chronic hepatitis C before and 3 months after the beginning of interferon alpha2b therapy. Serum levels of the activation product of terminal complement pathway, C5b-9, HCV RNA and IL-6 were also determined. IFN alpha treatment significantly (P<0.0001) increased the serum concentrations of both complement proteins. C5b-9 levels were found to significantly decrease during the same period of time. When the patients were divided into responders or non-responders (more or less than 50% decrease in plasma HCV RNA concentrations) C9 and C1-INH levels were elevated only in the responder patients. There was no correlation between the changes of IL-6 levels or the amounts of IFN alpha administrated on one hand, and the changes in the complement protein levels on the other. These findings suggest that the marked increase in the serum concentrations of the acute phase complement proteins is a secondary phenomenon due to the IFN alpha-caused diminution of the viral load and the resulting immune complex-induced complement activation.

[Minimally invasive adrenalectomy with posterior retroperitoneoscopy]. / Adrenalectomia minimálisan invazív formája hátsó retroperitoneoszkópos behatolásból.

Authors report a total of 14 adrenalectomies performed from a posterior (lumbotomy) approach, using minimally invasive retroperitoneoscopic technique. The "UltraCision" scalpel, an ultrasound activated cutter-coagulation device has been used for operative tissue dissection. Two cases were converted. The mean operating time of the successful 12 cases were 128 minutes. No mortality and no septic complication occurred. The mean operative blood loss of the 12 procedures were less than 100 ml. The mean hospitalisation was 3-5 days, and the complete recovery needed 2-3 weeks. On the basis of our own experiences and the ones of prospective, randomized clinical studies of the literature, the retroperitoneoscopic adrenalectomy from a posterior approach is recommended for the surgical treatment of benign tumours of the suprarenal gland with a size less than 5 cm diameter. The low conversion- and complication-rate, the minimal operative blood loss, the short hospitalization and quick recovery time all are the advantages of this method. It can be performed after previous abdominal operation and in cases with morbid obesity. The technique is suitable for bilateral adrenalectomies as well. This method is not justified for the removal of malignant and/or larger than 5 cm adrenal tumours. Coagulopathies are contraindications.

[Total mesorectal excision with ultrasonic coagulation knife ("UltraCision") in surgery of rectal cancer]. / Teljes mesorectum-kimetszés ultrahangos vágó-koaguláló késsel ("UltraCision") a végbélrák mútéteinél.

The authors report a total of 62 middle and low third rectal cancer cases operated on by total mesorectal excision by the method of Heald. The oncological basis of this procedure is the horizontal regional metastatization of rectal cancer. The total mesorectal excision facilitates, the low anterior resections and preservation of sphincter with an ultra-low colorectal, or coloanal anastomosis using the double stapling technique. In the authors' experience, the "UltraCision" cutting-coagulating device permits an atraumatic, bloodless and oncologically correct dissection. Using the double stapling technique, we succeeded in 60% of our middle- and low-third rectal cancer patients to perform a sphincter preserving low anterior resection. In 9 (28%) of the low third rectal cancer patients, preservation of the sphincter was possible with oncologically correct anterior resection and an ultra-low colo-anal anastomosis. Three anastomotic insufficiencies occurred, two of them healed on lotion-suction drainage, and one on the application of transient protective ileostomy. The literature data suggest a lower local recurrency rate after radical rectal cancer surgery, if total mesorectal excision is performed.

[A new method of tension-free inguinal hernia repair: "PROLENE hernia system" (PHS) (pilot study)]. / A feszülésmentes hernioplasztika új módszere: a "PROLENE Hernia System" (PHS) (Elózetes közlemény).

Authors report 10 case of tension free inguinal hernia repair with PHS double mesh grafts, used for the first time in Hungary. The operative technique is described in details. The first results are promising. Patients had minimal postoperative pain and recovery time was small. On the base of the results, the procedure is suitable for day surgery.

Antisense strategies: functions and applications in immunology.

The ability to manipulate gene expression by means of exogenously administered oligodeoxynucleotides complementary to specific sequences in the genome is clearly going to impact on many fields of biology and medicine including basic and clinical immunology. Also endogenously generated antisense RNA species are important in regulating gene expression. Antisense RNA has become a widely used tool for analysis of gene function and holds great promise for therapeutic use in the future. Thus, inhibition can take place on different levels (transcription, translation and aptamer binding). Avoiding unspecific reactions one has to use controls and well-designed oligonucleotides. Based on the studies described in this review, antisense oligonucleotides hold a great promise as a novel class of therapeutic agents in immunology as well as in oncology, neurology and viral infections.

Effect of blood storage on radiation-induced micronuclei in human lymphocytes.

To evaluate the effect of blood storage on the yield of micronuclei (MN) in both irradiated (in vivo and ex vivo) and unirradiated peripheral blood lymphocytes (PBL), we applied the MN assay in cytokinesis-blocked (CB) PBL obtained from healthy subjects (n=11), and from cancer patients (n=10) who were undergoing fractionated partial-body radiotherapy (xRT). The heparinized blood samples were exposed to 137Cs-irradiation (0 Gy or 2 Gy) immediately after blood collection and were stored upright in test tubes either at room temperature (22 degrees C) or in the refrigerator (5 degrees C). Duplicate whole blood cultures from each sample were set up at 0 h, 96 h, and 120 h after ex vivo irradiation. Giemsa (10%) stained slides were prepared from each culture. MN yield was determined per 1000 binucleated cells. As compared to that obtained from the corresponding fresh blood samples, we found that (1) the 22 degrees C blood storage temperature did not affect MN yields in PBL of either healthy subjects or cancer patients up to 96 h, either with or without ex vivo irradiation; and (2) while blood samples were stored at 5 degrees C, the MN yield increased significantly in PBL of healthy subjects (with or without ex vivo irradiation) at 120 h, and in cancer patients (with ex vivo irradiation) at 96 h and 120 h. Since handling of the blood sample is important for CBMN assay during shipment or in the laboratory, our findings showed that blood storage at 22 degrees C or at 5 degrees C up to 96 h appeared to provide insignificant variations of the MN results as compared to fresh blood samples. However, the 96 h of blood storage at 5 degrees C elevated the MN frequency in ex vivo irradiated PBL of cancer patients who were undergoing xRT.

Angioedema due to acquired C1-esterase inhibitor deficiency in a patient with Helicobacter pylori infection.

The first component of the classical pathway of the complement system, C1 is regulated by a serum protein, the C1-esterase inhibitor (C1-INH). Deficiency of this protein leads to the release of vasoactive mediators (C2 kinin and bradykinin) that increase vascular permeability and can induce edema formation in subcutaneous and submucosal tissues. The genetic variant of C1-INH deficiency is inherited as an autosomal dominant trait and causes hereditary angioneurotic edema. The acquired form of C1-INH deficiency is characterized by similar manifestations and can occur in association with lymphoproliferative diseases, malignancy, immune disorders, and infections. The authors present a case of acquired C1-INH deficiency in a patient with Helicobacter pylori infection. Complete eradication of this pathogen was followed by the resolution of symptoms and normalization of serum complement levels. It seems therefore probable that in this patient, acquired C1-INH deficiency was related to Helicobacter pylori infection. To our best knowledge, no similar observations have been published so far. Specific immune reactions are important contributing factors in H. pylori. Excessive consumption of complement by antibodies directed against H. pylori is a potential cause of C1-INH deficiency observed in our case.