Epidemiological analysis of pneumococcal serotype 19A in healthy children following PCV7 vaccination.

After the introduction of conjugate vaccines, a strong rearrangement of pneumococcal serotypes was observed globally. Probably most concerning was the emergence of serotype 19A, which has not only high invasive disease potential, but also high antibiotic resistance. In the current study we focused on the increased prevalence of serotype 19A after the PCV vaccination rate became widely used in Hungary. A total of 2262 children aged 3-6 years were screened for pneumococcus carriage using nasal swabs. Children were divided into two groups according to the vaccination rates, low level (group 1) vs. high level (group 2). While the carriage rate did not change over time (average 32·9%), the serotype distribution differed greatly in the two groups. The prevalence of serotype 19A increased >eightfold. Almost all 19A isolates had high-level macrolide resistance and elevated penicillin minimum inhibitory concentrations. Genotyping methods revealed that these new 19A isolates are different from the previously frequent Hungary19A-6 PMEN clone. Both the carriage rate and the overall penicillin and macrolide resistance remained stable over time, but while several serotypes were represented in group 1, serotype 19A alone was clearly dominant in group 2.

Is it Necessary to Perform Sentinel Lymph Node Biopsy in Thin Melanoma? A Retrospective Single Center Analysis.

Sentinel lymph node biopsy (SLNB) is a standard procedure for regional lymph node staging and still has the most important prognostic value for the outcome of patients with thin melanoma. In addition to ulceration, SLNB had to be considered even for a single mitotic figure in thin (<1 mm) melanoma according to AJCC7th guideline, therefore, a retrospective review was conducted involving 403 pT1 melanoma patients. Among them, 152 patients suffered from pT1b ulcerated or mitotic rate ≥ 1/ mm2 melanomas according to the AJCC7th staging system. SLNB was performed in 78 cases, of which nine (11.5%) showed SLN positivity. From them, interestingly, we found a relatively high positive sentinel rate (6/78-8%) in the case of thin primary melanomas ˂0.8 mm. Moreover, the presence of regression increased the probability of sentinel positivity by 5.796 fold. After reassessing pT stage based on the new AJCC8th, 37 pT1b cases were reordered into pT1a category. There was no significant relation between other characteristics examined (age, gender, Breslow, Clark level, and mitosis index) and sentinel node positivity. Based on our data, we suggest that mitotic rate alone is not a sufficiently powerful predictor of SLN status in thin melanomas. If strict histopathological definition criteria are applied, regression might be an additional adverse feature that aids in identifying T1 patients most likely to be SLN-positive. After reassessing of pT1b cases according to AJCC8th regression proved to be independent prognostic factor on sentinel lymph node positivity. Our results propose that sentinel lymph node biopsy might also be considered at patients with regressive thin (˂0.8 mm) melanomas.

Plasma concentrations of high-mobility group box protein 1, soluble receptor for advanced glycation end-products and circulating DNA in patients with acute pancreatitis.

AIMS: High-mobility group box protein 1 (HMGB1), a late-acting proinflammatory cytokine, is secreted actively by inflammatory cells, and released passively from necrotic cells. From the aspect that both inflammation and necrosis are involved in the pathogenesis in acute pancreatitis, the aim of the study was a joint investigation of the plasma concentrations of HMGB1, its soluble receptor for advanced glycation end-products (sRAGE), and the circulating DNA as a marker of cell death. METHODS: 62 patients with acute pancreatitis (30 mild, 32 severe), 20 patients with sepsis, and 20 healthy controls were enrolled in the study. HMGB1 and sRAGE plasma levels were measured by means of ELISA. Plasma DNA concentrations were estimated by real-time quantitative PCR for the beta-globin gene. RESULTS: The circulating HMGB1 level was significantly higher in patients with severe acute pancreatitis (13.33 +/- 2.11 ng/ml) than in healthy controls (0.161 +/- 0.03 ng/ml) or than in patients with mild pancreatitis (2.64 +/- 0.185 ng/ml). The plasma concentration of sRAGE was highest in patients with sepsis (2,210 +/- 252 pg/ml), while the levels of sRAGE correlated inversely with that of HMGB1 in patients with acute pancreatitis. The plasma DNA level was significantly elevated in patients with severe acute pancreatitis (2,206 +/- 452 ng/ml). CONCLUSION: A complex study of the plasma levels of HMGB1, sRAGE and circulating DNA can be informative in evaluations of acute pancreatitis with different levels of severity.

Relevance of the genetic polymorphism of NOD1 in Chlamydia pneumoniae seropositive stroke patients.

BACKGROUND AND PURPOSE: Chronic infections with certain pathogens, such as Chlamydia pneumoniae, and genetic parameters that influence inflammatory reactions have been suggested to contribute to ischaemic stroke. NOD1 is a potent cytosolic receptor for C. pneumoniae. The aim of this study was to investigate the genetic polymorphism of NOD1 from the aspect of the development of stroke. MATERIALS AND METHODS: A total of 280 patients with ischaemic stroke were enrolled in the study; 150 healthy blood donors served as controls. The G796A (E266K) NOD1 polymorphism was determined by restriction fragment length polymorphism. Chlamydia pneumoniae seropositivity was tested by ELISA. RESULTS: There was a significant difference in NOD1 G796A genotype distribution between the controls and the stroke patients with C. pneumoniae seropositivity. The AA homozygote and GA heterozygote mutant variants were detected in 16% (25 of 152) and in 50% (77 of 152) of the C. pneumoniae-positive stroke patients, as compared with 8% (6 of 84), and 28% (24 of 84), respectively, in the C. pneumoniae-positive healthy controls. (OR = 2.559; 95% CI = 1.105-6.517, P = 0.04 and OR = 2.567; 95% CI = 1.451-4.540 P < 0.001, respectively). The stroke patients with the large vessel pathology exhibited the highest frequency of the mutant allele A (51%). In contrast, amongst the C. pneumoniae-negative subjects, no difference in genotype frequency was observed between the stroke patients and the controls. CONCLUSION: Polymorphism in NOD1 G796A alone did not prove to be a risk factor for stroke in general, but in association with C. pneumoniae infection it appeared to be accompanied by an increased risk of the development of stroke.

Helicobacter pylori induces the release of alpha-defensin by human granulocytes.

OBJECTIVES: Little information is available on the potential role of alpha-defensins derived from neutrophils during H. pylori infection, or the effect of H. pylori on the alpha-defensin release. The effects of H. pylori on human granulocytes were investigated in vitro by flow cytometry and ELISA. Additionally we sought to identify by immunohistochemistry the alpha-defensins within the gastric mucosa of patients infected with H. pylori. MATERIALS AND METHODS: The intracellular expression of alpha-defensin in human granulocytes and in mononuclear cells was determined by flow cytometry. Induction of alpha-defensin release from granulocytes, mononuclear cells, or from whole blood cultures by H. pylori was detected by measuring the HNP1-3 (alpha-defensin) concentrations in the supernatants by ELISA. Immunohistochemistry was used to identify HNP1-3 in infiltrating neutrophils in the gastric mucosa of eight patients. RESULTS: A considerable intracellular alpha-defensin staining was observed in granulocytes. Stimulation of granulocytes with H. pylori resulted in a decrease in intracellular staining which was due to the extracellular release of alpha-defensin. In whole blood cultures H. pylori infection resulted in significantly high alpha-defensin concentrations (131623 +/- 13986 pg/ml), which were mainly due to the activity of the granulocytes with only a minor amount furnished by the mononuclear cells. In H. pylori-infected mucosa, infiltrating neutrophils showed intense immunostaining with anti-HNP1-3. The intensity of alpha-defensin staining varied parallel with the density of H. pylori in the biopsy samples. CONCLUSIONS: H. pylori induce alpha-defensin release from granulocytes which may well be important in local host response to H. pylori infection in gastroduodenal diseases.

Lung Transplantation in Hungary From Cardiac Surgeons' Perspective.

Thoracic organ transplantation made a fresh start in Hungary with the first double lung transplant in December 2015. This major leap in Hungarian transplantation was preceded by almost 10 years of preparation, new infrastructure development, and structural changes not only at the organizational level but in human resources as well. In the following years, until recently, altogether 47 lung transplants were performed on 24 men and 23 women. The underlying pathologies were as follows: chronic obstructive pulmonary disease, 25; cystic fibrosis, 11; idiopathic pulmonary fibrosis, 7; as well as other diseases, including bronchiectasis, eosinophilic granuloma, lymphangioleiomyomatosis, and primary pulmonary hypertension in 4 cases. The youngest recipient was 13 and the oldest was 65 years old. Overall survival rates at 30 days and at 1 year were 96% and 82%, respectively. No patients were lost in the cystic fibrosis and other diseases group, whereas the 1-year survival rates of the chronic obstructive pulmonary disease and idiopathic pulmonary fibrosis groups were 73% and 71%, respectively. The results show the robustness and viability of the program, although there is still opportunity for further improvement. In this short paper, we summarize the fields of possible further cooperation of thoracic and cardiac teams as well as future challenges facing the new Hungarian lung transplant program.

Antibody-Mediated Rejection in a Multiple Lung Transplant Patient: A Case Report.

Lung transplant is an effective way to treat many end-stage lung diseases. However, one of the main barriers of allograft organ transplant is still the immunologic rejection of transplanted tissue, which is a response of the HLA molecules. Rejection is a complex process involving both T-cell-mediated delayed-type hypersensitivity reactions and antibody-mediated hypersensitivity reactions to histocompatibility molecules on foreign grafts. We report the case of a 25-year-old female patient with cystic fibrosis who underwent 2 lung transplants because of her initial diagnosis and appearance of bronchiolitis obliterans syndrome after the first transplant. Only 13 months after the second transplant, despite the therapies applied, a new rejection occurred associated with high mean fluorescent intensity donor-specific antibody levels, which resulted later in the death of the patient. The present case draws attention to the importance of matching HLA molecules between donor and recipient in addition to immunosuppressive therapy.

Depressed activation of the lectin pathway of complement in hereditary angioedema.

The possibility of simultaneous measurement of the classical pathway (CP), mannan-binding lectin (MBL)--lectin pathway (LP) and alternative pathway (AP) of complement activation by the recently developed Wielisa method allowed us to investigate the in vivo significance of the C1-inhibitor (C1INH) in three complement activation pathways. Functional activity of the CP, LP and AP were measured in the sera of 68 adult patients with hereditary angioedema (HAE) and 64 healthy controls. In addition, the level of C1q, MBL, MBL-associated serine protease-2 (MASP-2), C4-, C3- and C1INH was measured by standard laboratory methods. MBL-2 genotypes were determined by polymerase chain reaction. Besides the complement alterations (low CP and C1INH activity, low C4-, C1INH concentrations), which characterize HAE, the level of MASP-2 was also lower (P = 0.0001) in patients compared with controls. Depressed LP activity was found in patients compared with controls (P = 0.0008) in homozygous carriers of the normal MBL genotype (A/A), but not in carriers of variant genotypes (A/O, O/O). Activity of CP correlated with LP in patients (Spearman's r = 0.64; P < 0.0001), but no significant correlation was found in the control group and no correlation with AP was observed. In contrast, the activity of CP and AP correlated (Spearman's r = 0.47; P < 0.0001) in healthy controls, but there was no significant correlation in the HAE patients. We conclude that the activation of LP might also occur in subjects with C1INH deficiency, which is reflected by the low MASP-2 and C4 levels.

Persistent sexual arousal in a woman with associated cardiac defects and raised atrial natriuretic peptide.

The persistent sexual arousal syndrome (PSAS) is a newly described entity where the woman becomes involuntarily genitally aroused for extended periods of time in the absence of sexual desire and is distressed by this situation. The cause of this sexual problem is not well understood. We describe such a case where the subjective feelings were confirmed by observing genital engorgement. In her case, PSAS came on after initiation of fludrocortisone given for hypotension and bradycardia that was associated with an atrial septal defect (ASD). We argue that the combined effect of the ASD and fludrocortisone may be associated with an increase in her levels of atrial natriuretic peptide (ANP). ANP causes profound vasodilation and vascular leakage. We postulate that the high serum levels of ANP in her case may be contributory to her PSAS.

Clinical experience with zidovudine for patients with acquired immune deficiency syndrome and acquired immune deficiency syndrome-related complex.

We have treated 113 patients with zidovudine since its licensure, 80 with acquired immunodeficiency syndrome and 33 with acquired immunodeficiency syndrome-related complex. This paper reports on the efficacy and toxicity observed in these patients. Improved well-being, reduced frequency and severity of opportunist infections were notable in the first year of follow-up. More rapid improvement in pulmonary physiological tests during recovery from Pneumocystis carinii pneumonia was also observed in treated patients. Patients with lower initial platelet counts showed early increases in platelet counts. There was a consistent fall in human immunodeficiency virus (HIV) p24 antigen during treatment, although not always to undetectable levels. CD4 cell counts showed a rise in the first months of treatment but these were not sustained, despite continuing clinical benefit. Neuropsychological and clinical evidence of benefit in HIV encephalopathy are described. We have analysed the factors influencing marrow toxicity and have found that low CD4 count and the intercurrent use of ganciclovir and dapsone increase myelotoxicity. We describe the clinical and biochemical features of the myopathy associated with long-term use of zidovudine and summarise our findings on dose-reduction associated meningo-encephalitis.

Configurative correlation and conformational analysis of strictosidine and vincoside derivatives

On the basis of the configuration of C-15 of the secologanin unit, using detailed NMR analysis, the configuration of C-3, the solution conformation around C-14, and the glucosidic bridge, as well as those of the dihydropyran and tetrahydropyridine rings, were determined in the vincosamide and strictosamide derivatives 4b and 5b. The stereochemical analysis was extended by chemical correlation to the 4-benzylated strictosidine and vincoside derivatives 3c and 3d. Experimental proof was presented for the interpretation of the "anomalous" chemical shift of acetylated strictosamide derivatives.

Determinants of unsafe sex in women.

We aimed to identify determinants of condom usage and unsafe sex in women having sex with a new partner. One hundred women attending either a genitourinary medicine (GUM) clinic or a family planning clinic participated in the study. Respondents were interviewed about last 3 new male partners, from the beginning of the sexual relationship through its development, if any. Data analysis was primarily qualitative, quantitative analysis was conducted where appropriate. Alternative contraceptive use was the most commonly reported determinant of condom usage overall. The most commonly reported determinant of condom use for prophylaxis was the woman's perception of her partner and the risks he presented. Models of risky sexual behaviour have focused on the individual's generalized estimation of risks of acquiring STDs. Existing models are poor predictors of risky sexual behaviour. We propose that it is the perceived risk presented by a particular individual partner, not global risk, which influences behaviour. An individual risk model is put forward.

A review of physical and psychological factors in vulvar vestibulitis syndrome.

This review is based on a MEDLINE search of all papers on vulvar vestibulitis syndrome (VVS) published 1995-2000. The causation, natural history and prevalence of VVS are unknown. There is no convincing evidence that VVS is the result of an infection or of an allergy. It has been proposed that it is an atypical pain syndrome but there is currently no clear evidence that this is so. The usual diagnostic criteria used in VVS are of doubtful discriminative value. Findings from biopsies of women with VVS are inconsistent. While there is some evidence to suggest that women with VVS attending clinics differ psychologically from normal controls, it is not clear whether these differences reflect the effects of VVS, are the result of patient selection or influence the development of the disease. Several treatments, including biofeedback, psychosexual treatment and surgery have been reported to be successful in some patients but there is a lack of proper placebo-controlled trials on which to base estimates of efficacy. There is a vital need for further, high-quality, research in this area.

[Idiopathic thrombocytopenia caused by varicella]. / Varicella által kiváltott idiopathiás thrombocytopenia.

The authors deal with the case of a 6-year old girl in whom thrombocytopenia developed with haemorrhagic symptoms as a rare complication of varicella. They give a short review about the reasons and the etiology of idiopathic thrombocytopenic purpura, and deal with the mechanism of thrombocytopenia caused by varicella.

[Adverse effects of orthodontic treatment]. / Fogszabályozó kezelések során fellépö káros következmények.

The authors reviewed the adverse effects. The main effects are: demineralisation; gingivitis hyperplastica, mucogingival and marginal attachment bone loss, long-term-effects; pulp damage and devitalisation of teeth; apical and marginal root resorption; temporomandibular dysfunction.

Psychological factors in recurrent genital herpes.

OBJECTIVES: To review recent research into psychological aspects of genital herpes and assess possible implications for clinical practice. METHODS: Review of all papers in the field on Medline 1985-96. RESULTS: Much attention has been paid to possible links between stress and recurrent genital herpes. There is no convincing evidence that stress in itself causes recurrences. It may be that recurrences are preceded by a prodromal period of altered mood. Patients with recurrences show considerable stress as a result of the disease, although most individuals eventually adjust psychologically. The impact of social support on adjustment remains unclear. The little evidence available suggests that antiviral treatments can help adjustment and the effects may perhaps outlast the period of active treatment. CONCLUSIONS: Existing research gives some clues to optimal patient management but there is a need for future research to focus much more clearly on clinical issues, particularly on means of alleviating psychological distress and on the impact of antivirals.