Screening of more than 2000 Hungarian healthcare workers' anti-measles antibody level: results and possible population-level consequences.

Due to the European measles epidemic and the increased number of imported cases, it can be theorised that the risk of exposure among Hungarian healthcare workers (HCWs) has increased. In 2017, the increased measles circulation in the region led to the emergence of smaller local and hospital epidemics. Therefore, our objective was to determine the herd immunity in the high-risk group of HCWs. A hospital-based study of detecting anti-measles IgG activity was performed in 2017 and included 2167 employees of the Military Medical Centre (Hungary). The screening of HCWs presented a good general seropositivity (90.6%). The highest seroprevalence value (99.1%) was found in the age group of 60 years or older. The lowest number of seropositive individuals was seen in the 41-45 years (86.2%) age group, indicating a significant herd immunity gap between groups. Regarding the Hungarian data, there might be gaps in the seroprevalence of the analysed HCWs, implying that susceptible HCWs may generate healthcare-associated infections. This study suggests that despite the extensive vaccination and high vaccine coverage, it is still important to monitor the level of protective antibodies in HCWs, or in a representative group of the whole population of Hungary, and possibly in other countries as well.

Is ionized oxygen negatively or positively charged more effective for carboxyhemoglobin reduction compare to medical oxygen at atmospheric pressure?

Carbon monoxide (CO) reversibly binds to hemoglobin forming carboxyhemoglobin (COHb). CO competes with O(2) for binding place in hemoglobin leading to tissue hypoxia. Already 30 % saturation of COHb can be deadly. Medical oxygen at atmospheric pressure as a therapy is not enough effective. Therefore hyperbaric oxygen O(2) inhalation is recommended. There was a question if partially ionized oxygen can be a better treatment at atmospheric pressure. In present study we evaluated effect of partially ionized oxygen produced by device Oxygen Ion 3000 by Dr. Engler in elimination of COHb in vitro experiments and in smokers. Diluted blood with different content of CO was purged with 5 l/min of either medicinal oxygen O(2), negatively ionized O(2) or positively ionized O(2) for 15 min, then the COHb content was checked. In vivo study, 15 smokers inhaled of either medicinal oxygen O(2) or negatively ionized O(2), than we compared CO levels in expired air before and after inhalation. In both studies we found the highest elimination of CO when we used negatively ionized O(2). These results confirmed the benefit of short inhalation of negatively ionized O(2), in frame of Ionized Oxygen Therapy (I O(2)Th/Engler) which could be used in smokers for decreasing of COHb in blood.

Effect of reoxygenation on the electrical stability of the rat heart in vivo: a chronobiological study.

Reoxygenation following hypoxic episodes can increase the risk for the development of ventricular arrhythmias, which, in addition to circadian aspects of reoxygenation arrhythmias has not been studied extensively. The aim of the present study was to evaluate circadian changes in the electrical stability of the rat heart during reoxygenation following a hypoventilatory episode. The electrical stability of the heart, defined in the present study as the ventricular arrhythmia threshold (VAT), was measured at 3 h intervals at clock times 09:00, 12:00, 15:00, 18:00, 21:00, 24:00, 03:00, 06:00 and 09:00 during 20 min hypoventilation (20 breaths/min, tidal volume = 0.5 ml/100 g body weight [n=17]) and subsequent 20 min reoxygenation (50 breaths/min, tidal volume = 1 ml/100 g body weight [n=4]) intervals. The experiments were performed using pentobarbital-anesthetized (40 mg/kg intraperitoneally) female Wistar rats that first underwent a four-week adaptation to a 12 h light:12 h dark regimen. Detailed analysis showed that circadian VATs changed to biphasic rhythms at 10 min of hypoventilation. The VAT circadian rhythms were observed immediately following the commencement of reoxygenation, with the highest values measured between 12:00 and 15:00, and the lowest values between 24:00 and 03:00. These results suggest that myocardial vulnerability is dependent on the light:dark cycle and characteristics of pulmonary ventilation.

Hemorheology and circulation.

The main functions of the blood are the transport, and delivery of oxygen and nutrients, removal of carbon dioxide and waste products of metabolism, distribution of heat and signals of immune system. They are provided by circulation due to the driving force of the heart. Circulation of the blood depends on its rheological properties of the blood as well as on characteristics of the vessels through which the blood passes. The blood flow resistance is influenced by the complicated architecture of the vascular network and flow behaviour of blood components - blood cells and plasma. The obtained data based on analysis of influences on blood flow are differentiated in the dependence on place and level of investigation. At a macroscopic level the blood appears to be a liquid material, but at a microscopic level the blood appears to be a material with microscopic solid particles of varying size - various blood cells. From this point of view, we have to consider the blood flow in large vessels, and also on the level of microvessels. This division of facts of hemorheology is somewhat simplistic, but is very useful from the point of view of explanation and comprehension.

Ionic hemolysis behavior of erythrocytes in rats of both sexes.

Erythrocyte microrheology changes were measured by cation-osmotic haemolysis in Wistar albino rats of both sexes. Erythrocyte membrane biophysical properties were estimated using the method of cation-osmotic haemolysis (COH) described by Nicak and Mojzis [Comp. Haematol. Int. 2 (1992), 84-86]. COH in male rats was higher in low ionic strength medium (spectrin skeleton) but without of statistical significance. The significantly higher COH in male rats in comparison with female rats was observed in higher ionic strength media. COH and erythrocyte deformability is also discussed. We suggest that changes in biophysical state of spectrin skeleton are followed by changes in lipid bilayer properties.

Contribution of germline MLH1 and MSH2 mutations to lobular carcinoma in situ of the breast.

Lobular carcinoma in situ (LCIS) is an unusual histological pattern of non-invasive neoplastic disease of the breast occurring predominantly in women aged between 40 and 50 years. LCIS is frequently multicentric and bilateral suggesting a genetic basis to the disease. The high frequency of microsatellite instability in lobular breast cancers, coupled with increased risk of breast cancer associated with germline mismatch repair gene mutations raises the possibility that mutations MSH2 or MLH1 might confer susceptibility to LCIS. To explore this possibility we have examined a series of 71 LCIS patients for germline MSH2 and MLH1 mutations. No mutations were detected in MSH2. Two sequence variants were identified in MLH1. The first was a CTT-->CAT substitution, codon 607 (exon 16) changing leucine to histidine. The other mutation detected in MLH1 was a TAC-->TAA substitution codon 750 (exon 19) creating a stop codon, predicted to generate a truncated protein. These findings suggest that mutations in MLH1 may underlie a subset of LCIS cases.

Linkage analysis for major histocompatibility complex-related genetic susceptibility in familial chronic lymphocytic leukemia.

Chronic lymphocytic leukemia (CLL) shows evidence of familial aggregation, but the genetic basis is poorly understood. The existence of a linkage between HLA and Hodgkin lymphoma, another B-cell disorder, coupled with the fact that CLL is frequently associated with autoimmune disease, led to the question of whether the major histocompatibility complex (MHC) region is involved in familial cases of CLL. To examine this proposition, 5 microsatellite markers on chromosome 6p21.3 were typed in 28 families with CLL, 4 families with CLL in association with other lymphoproliferative disorders, and 1 family with splenic lymphoma with villous lymphocytes. There was no evidence of linkage in these families to chromosome 6p21.3. The best estimates of the proportions of sibling pairs with CLL that share 0, 1, or 2 MHC haplotypes were not significantly different from the null expectation. This implies that genes within the MHC region are unlikely to be the major determinants of familial CLL. (Blood. 2000;96:3982-3984)

Familial chronic lymphocytic leukaemia: a survey and review of published studies.

B-cell chronic lymphocytic leukaemia (CLL) is the most common form of leukaemia. To gain insight into the role of inherited factors in the disease, we have conducted a survey of the family histories of 268 CLL patients and have reviewed published familial cases and epidemiological studies. The results of our survey and published studies strongly support the hypothesis that a subset of the disease can be ascribed to a genetic predisposition. The most likely genetic model for inherited predisposition appears to be dominantly acting genes with pleiotropic effects because in many families CLL appears to be associated with other lymphoproliferative disorders.

Lobular carcinoma in situ of the breast is not caused by constitutional mutations in the E-cadherin gene.

Lobular carcinoma in situ (LCIS) is an unusual histological pattern of non-invasive neoplastic disease of the breast occurring predominantly in women aged between 40 and 50 years. LCIS is frequently multicentric and bilateral, and there is evidence that it is associated with an elevated familial risk of breast cancer. Although women with LCIS suffer an increased risk of invasive breast disease, this risk is moderate suggesting that LCIS may result from mutation of a gene or genes conferring a high risk of LCIS, but a lower risk of invasive breast cancer. The high frequency of somatic mutations in E-cadherin in LCIS, coupled with recent reports that germline mutations in this gene can predispose to diffuse gastric cancer, raised the possibility that constitutional E-cadherin mutations may confer susceptibility to LCIS. In order to explore this possibility we have examined a series of 65 LCIS patients for germline E-cadherin mutations. Four polymorphisms were detected but no pathogenic mutations were identified. The results indicate that E-cadherin is unlikely to act as a susceptibility gene for LCIS.

Contribution of the MHC region to the familial risk of coeliac disease.

Susceptibility to coeliac disease is genetically determined by possession of specific HLA-DQ alleles, acting in concert with one or more non-HLA linked genes. The pattern of risk seen in sibs and twins in coeliac disease is most parsimonious with a multiplicative model for the interaction between the two classes of genes. Based on a sib recurrence risk for coeliac disease of 10% and a population prevalence of 0.0033, the sib relative risk is 30. To evaluate the contribution of the MHC region to the familial risk of coeliac disease, we have examined haplotype sharing probabilities across this region in 55 coeliac disease families. Based on these probabilities the sib relative risk of coeliac disease associated with the MHC region is 3.7. Combining these results with published data on allele sharing at HLA, the estimated sib relative risk associated with the MHC region is 3.3. Therefore, the MHC genes contribute no more than 40% of the sib familial risk of coeliac disease and the non-HLA linked gene (or genes) are likely to be the stronger determinant of coeliac disease susceptibility.

Linkage analysis for ATM in familial B cell chronic lymphocytic leukaemia.

B cell chronic lymphocytic leukaemia (CLL) shows evidence of familial aggregation, but the inherited basis is poorly understood. Mutations in the ATM gene have been demonstrated in CLL. This, coupled with a possibly increased risk of leukaemia in relatives of patients with Ataxia Telangiectasia, led us to question whether the ATM gene is involved in familial cases of CLL. To examine this proposition we typed five markers on chromosome 11q in 24 CLL families. No evidence for linkage between CLL and ATM in the 24 families studied and the best estimates of the proportion of sibling pairs that share no, one or both haplotypes at ATM were not different from their null expectations. This would imply that ATM is unlikely to make a significant contribution to the three-fold increase in risk of CLL seen in relatives of patients.

Low frequency of germline E-cadherin mutations in familial and nonfamilial gastric cancer.

Little is known about the relative contributions of genetic and environmental factors to the development of gastric cancer. Mutations in the cell adhesion molecule E-cadherin are recognized to be associated with the development of undifferentiated, diffuse and invasive gastric cancers. A recent study of two gastric cancer families has shown that germline mutations in the E-cadherin gene can be causative (Guilford P et al, Nature 1998; 26: 402-405). We have examined the E-cadherin gene for constitutive mutations in a systematic series of 106 gastric cancer patients, 10 with a family history of the disease and 96 sporadic cases. No pathogenic mutations were observed in any of the 106 patients. The results indicate that germline mutations in E-cadherin will not account for more than 3% of gastric cancers.

Non-albicans Candida species isolated from plastic devices.

In this work we point out an occurrence of non-albicans Candida species isolated from catheters, cannulas and drains. We detected eight non-albicans Candida species in 49 examined samples: C. parapsilosis (n = 26), C. tropicalis (n = 12), C. krusei (n = 4), C. claussenii, C. mesenterica (n = 2 for each), C. guilliermondii, C. kefyr and C. lusitaniae (n = 1 for each). Material examined from children hospitalized in intensive care units was the most frequent. Eight samples were from the oncology department, seven from the surgery department, six from the anaesthesiology department, four from the dialysis unit, two from the hematology department, one from the internal medicine department and one from the stomatology department. We examined cannula scraping 26 times (53%), catheter scraping 14 times (28.6%) and drain scraping nine times (18.4%).

Linkage analysis of candidate regions for coeliac disease genes.

A strong HLA association is seen in coeliac disease [specifically to the DQ(alpha1*0501,beta1*0201 heterodimer], but this cannot entirely account for the increased risk seen in relatives of affected cases. One or more genes at HLA-unlinked loci also predispose to coeliac disease and are probably stronger determinants of disease susceptibility than HLA. A recent study has proposed a number of candidate regions on chromosomes 6p23 (distinct from HLA), 6p12, 3q27, 5q33.3, 7q31.3, 11p11, 15q26, 19p13.3, 19q13.1, 19q13.4 and 22cen for the location of a non-HLA linked susceptibility gene. We have examined these regions in 28 coeliac disease families by linkage analysis. There was excess sharing of chromosome 6p markers, but no support for a predisposition locus telomeric to HLA. No significant evidence in favour of linkage to coeliac disease was obtained for chromosomes 3q27, 5q33.3, 7q31.3, 11p11, 19p13.3, 19q13.1, 19q13.4 or 22cen. There was, however, excess sharing close to D15S642. The maximum non-parametric linkage score was 1.99 (P = 0.03). Although the evidence for linkage of coeliac disease to chromosome 15q26 is not strong, the well established association between coeliac disease and insulin dependent diabetes mellitus, together with the mapping of an IDDM susceptibility locus (IDDM3) to chromosome 15q26, provide indirect support for this as a candidate locus conferring susceptibility to coeliac disease in some families.

Incidence of degenerate fibres in the dorsal column nuclei after ligation of the abdominal aorta.

It was investigated the incidence of damaged nerve fibres in the gracile nucleus and the cuneate nucleus of the dog following an intermittent ligation of the abdominal aorta and 3-day survival. The incidence of damaged fibres was studied at three levels, i.e. the caudal part of the gracile nucleus, the cell-nest region of the gracile nucleus and the region just before the beginning of the central canal. The largest number of disintegrated nerve fibres was found in the cell-nest region. It was observed, that the incidence of damaged fibres diminished both caudally and cranially. When comparing the region just before the beginning of the gracile nucleus with the caudal part of the gracile nucleus it was stated, that the higher density of decomposed fibres was in the region just below the obex. In common there were fewer disintegrated fibres in the cuneate than in the gracile nucleus.

Changes in spinal ganglia satellite and Schwann cells after aortic occlusion.

Ultrastructural ischemic changes of satellite and Schwann cells in lumbar spinal ganglia were studied in dog after single 80-minute and repeated 40-minute ligation of the abdominal aorta 3-48 hours survival. Satellite cells undergo greater changes than the Schwann cells. After a single ligation for eighty minutes, the satellite cell cytoplasm reveals lengthened or slightly vacuolated cisterns of the endoplasmic reticulum and more numerous lysosomes. The adneuronal surface of satellite cells shows retraction of the processes. Schwann cells, investing large myelinated axons contain markedly vacuolated endoplasmic reticulum and some osmiophilic inclusions. Three hours after repeated ligation the density of satellite cell cytoplasm is decreased and the cell processes of the adneuronal surface are less numerous. Some satellite cells containing large vacuoles undergo acute degeneration. Three hours after repeated ligation the Schwann cell cytoplasm reveals numerous lamellar bodies. Following 1-2 days survival after repeated ligation, strongly vacuolized satellite cells or those with lower cytoplasmic density are more frequent, but also hypertrophic satellite cells are visible. The changes of the Schwann cells are less advanced and manifest by the vacuolization of the organelles and the presence of lamellar bodies and other osmiophilic inclusions.