Choroiditis and meningitis in experimental murine infection withListeria monocytogenes

In a study of central nervous system involvement in experimental listeriosis 27 Swiss CD1 mice were inoculated subcutaneously withListeria monocytogenes. Systemic infection developed, as shown by the isolation ofListeria monocytogenes and histopathological lesions in the spleen and liver. In the central nervous system a mixed inflammatory infiltration in the ventricular system, especially in the choroid plexus, and leptomeningitis were the most relevant lesions. Inflammatory lesions were associated with the presence ofListeria monocytogenes, as demonstrated by a positive anti-Listeria monocytogenes immunoperoxidase reaction within phagocytic cells. It is suggested that choroiditis and meningitis developed as a consequence of hematogenous dissemination ofListeria monocytogenes within mononuclear phagocytes and penetration of these cells into the ventricular system through the choroid plexus.     

A microbiological, histopathological and immunohistological study of the intragastric inoculation of Listeria monocytogenes in mice.

The course of murine infection after intragastric inoculation of L. monocytogenes was investigated by immunocytochemical, histopathological and microbiological techniques. L. monocytogenes antigen was observed in epithelial cells of intestinal mucosa overlying Peyer's patches, but not in mucosa devoid of them. This suggests that penetration of L. monocytogenes into the host organism may take place through epithelium overlying Peyer's patches. The efficiency of bacterial penetration appeared to be low, as shown by the small amounts of L. monocytogenes antigen detected and the low counts of bacteria in organs. Gross or histopathological lesions in the intestinal tract were not observed. The presence of L. monocytogenes in spleen, liver and in maxillary and mesenteric lymph nodes, confirmed that the systemic course of infection by this route of inoculation is similar to that of the parenteral routes. The results emphasize the subclinical character of murine listeriosis by the oral route.     

Expression of intercellular adhesion molecule-3 (ICAM-3/CD50) in malignant lymphoproliferative disorders and solid tumors

ICAM-3/CD50 is a recently described LFA-1 counter receptor that seems to play an important role in the initiation of immune responses. In this study we have examined the expression of ICAM-3/CD50 in a large series of human neoplasms including 101 Non-Hodgkin's lymphomas (NHL), 26 Hodgkin's disease, and 38 solid tumors to define the distribution patterns of this molecule in malignant neoplasms and their possible correlation with clinical and pathological characteristics of the patients. In NHL, ICAM-3/CD50 was expressed in almost all the tumors with a tendency to be lost in high grade lymphomas. Reed-Sternberg cells and their variants in Hodgkin's disease were always negative independently of the histological subtype of the disease. No expression was observed in tumor epithelial cells of the 38 solid tumors examined. Strong endothelial cell staining was observed in 31% of the NHL and 31% of Hodgkin's disease. ICAM-3 expression in these cases was restricted to small tumor vessels. ICAM-3 expression in endothelial cells of NHL was significantly more frequent in high grade (40%) than in low grade lymphomas (14%) (p=0.012). In addition, tumor vessels were also positive in 29% of solid rumors independently of the histological type. No correlation was observed between ICAM-3 expression in tumor or endothelial cells and other clinical and pathological characteristics of the patients. These findings indicate that ICAM-3 expression in human tumors is restricted to hematological neoplasms with a tendency to be lost in high grade lymphomas and Hodgkin's disease. ICAM-3 is also expressed by endothelial cells from tumor-associated neovascularization in both lymphoid and solid tumors.     

Escherichia coli serotype O15:K52:H1 as a uropathogenic clone

To clarify the clinical and bacteriological correlates of urinary-tract infection (UTI) due to Escherichia coli O15:K52:H1, during a 1-year surveillance period we prospectively screened all 1, 871 significant E. coli urine isolates at the Hospital de la Santa Creu i Sant Pau, Barcelona, Spain, for this serotype and assessed the epidemiological features of community-acquired UTI due to E. coli O15:K52:H1 versus other E. coli serotypes. We also compared the 25 O15:K52:H1 UTI isolates from the present study with 22 O15:K52:H1 isolates from other, diverse geographic locales and with 23 standard control strains (8 strains from the ECOR reference collection and 15 strains of nonpathogenic O:K:H serotypes) with respect to multiple phenotypic and genotypic traits. Although E. coli O15:K52:H1 caused only 1.4% of community-acquired E. coli UTIs during the surveillance period, these UTIs were more likely to present as pyelonephritis and to occur in younger hosts, with similar risk factors, than were UTIs due to other E. coli serotypes. Irrespective of geographic origin, E. coli O15:K52:H1 strains exhibited a comparatively restricted repertoire of distinctive virulence factor profiles (typically, they were positive for papG allele II, papA allele F16, and aer and negative for sfa, afa, hly, and cnf1), biotypes, ribotypes, and amplotypes, consistent with a common clonal origin. In contrast, their antimicrobial resistance profiles were more extensive and more diverse than those of control strains. These findings indicate that E. coli O15:K52:H1 constitutes a broadly distributed and clinically significant uropathogenic clone with fluid antimicrobial resistance capabilities.     

A severe autosomal-dominant periodic inflammatory disorder with renal AA amyloidosis and colchicine resistance associated to the MEFV H478Y variant in a Spanish kindred: an unusual familial Mediterranean fever phenotype or another MEFV-associated periodic inflammatory disorder?

Familial Mediterranean fever (FMF) is an autosomal recessive disease characterized by recurring short attacks of fever and serositis. Secondary AA amyloidosis is the worst complication of the disease and often determines the prognosis. The MEFV gene, on chromosome 16p13.3, is responsible for the disease and around 30 mutations have been reported to date. Colchicine is the standard FMF treatment today, and prevents both attacks and amyloid deposition in 95% of patients. Here we describe a three-generation Spanish kindred with five family members affected by a severe periodic inflammatory disorder associated with renal AA amyloidosis and colchicine unresponsiveness. Clinical diagnosis of definite FMF disease was made based on the Tel-Hashomer criteria set. Genetic analyses revealed that all subjects were heterozygous for the new H478Y MEFV variant, segregating with the disease. In addition, mutations in the TNFRSF1A and CIAS1/PYPAF1/NALP3 genes, related to the dominantly inherited autoinflammatory periodic syndromes, were ruled out. However, the dominant inheritance of the disease, the long fever episodes with a predominant joint involvement, and the resistance to colchicine in these patients raise the question of whether the periodic syndrome seen in this kindred is a true FMF disease with unusual manifestations or rather another MEFV-associated periodic syndrome. We conclude that the new H478Y MEFV mutation is the dominant pathological variant causing the inflammatory periodic syndrome in this kindred and that full-length analyses of the MEFV gene are needed to obtain an adequate diagnosis of patients with clinical suspicion of a hereditary periodic fever syndrome, especially those from non-ancestral populations.     

Induction of interleukin 2 (IL2) and interferon-γ and enhancement of IL2 receptor expression by a CD26 monoclonal antibody

The ability of the 134-2C2 monoclonal antibody (mAb; CD26) to transmit an activation signal and to affect T cell proliferation has been studied. The 134-2C2 mAb, although not being mitogenic by itself, is able to increase the proliferation of purified T cells in the presence of exogenous interleukin 2 (IL2) or phorbol 12-myristate 13-acetate (PMA). No effect of our mAb was observed on the proliferation of T cells induced by other stimuli such as Sepharose-bound CD3 mAb, phytohemagglutinin or calcium ionophore. Since the co-stimulatory effect of 134-2C2 mAb on PMA-induced T cell proliferation was strongly inhibited by an anti-Tac antibody, its involvement on the IL2/IL2 receptor pathway was investigated. An increased IL2 secretion in T cells cultured with PMA plus 134-2C2 mAb was observed and Northern blot analysis showed that the mAb 134-2C2 acts synergistically with PMA favoring the induction of both IL2 and interferon-γ mRNA synthesis, as well as the enhancement of IL2 receptor and transferrin receptor mRNA expression. Studies on mechanisms implicated in signal transduction showed that 134-2C2 mAb modifies neither intracellular calcium levels nor phosphoinositide breakdown. Additionally, no effect was exerted on protein kinase C translocation. These data suggest that the CD26 antigen is involved in T cell activation in an IL2/IL2 receptor-dependent pathway.     

Expression of the proteoglycans versican and mel-CSPG in dysplastic nevi

Nevi with architectural disorder and cytologic atypia of melanocytes (NAD) (also called dysplastic nevi) have been controversial with regard to their relationship with melanoma risk and to their gradation in 3 degrees of atypia. Versican and the melanoma-associated proteoglycan (mel-CSPG) are 2 major proteoglycans expressed by malignant melanoma, and they have a role in the regulation of cell adhesion, migration, and differentiation. We evaluated the differences in versican and mel-CSPG expression in nevi, NAD with several degrees of atypia, and primary malignant melanoma. Immunoreactivity for versican was negative in benign melanocytic nevi, positive in NAD (ranging from weakly to intensely positive), and intensely positive in malignant melanoma. Immunostaining for mel-CSPG was negative in benign melanocytic nevi and mild to moderately positive in NAD and melanoma. Our results suggest that versican expression may be of value for distinguishing NAD from benign melanocytic nevi and for distinguishing severe NAD from mild and moderate NAD.     

Severe hypoxia decreases oxygen uptake relative to intensity during submaximal graded exercise

Summary The effect of severe acute hypoxia (fractional concentration of inspired oxygen equalled 0.104) was studied in nine male subjects performing an incremental exercise test. For power outputs over 125 W, all the subjects in a state of hypoxia showed a decrease in oxygen consumption ( O₂) relative to exercise intensity compared with normoxia (P < 0.05). This would suggest an increased anaerobic metabolism as an energy source during hypoxic exercise. During submaximal exercise, for a given O₂, higher blood lactate concentrations were found in hypoxia than in normoxia (P < 0.05). In consequence, the onset of blood lactate accumulation (OBLA) was shifted to a lower O₂ ( O₂ 1.77 l·min^–1 in hypoxia vs 3.10 l·min^–1 in normoxia). Lactate concentration increases relative to minute ventilation ( _E) responses were significantly higher during hypoxia than in normoxia (P < 0.05). At OBLA, _E during hypoxia was 25% lower than in the normoxic test. This study would suggest that in hypoxia subjects are able to use an increased anaerobic metabolism to maintain exercise performance.     

Abordajes en cirugía tiroidea

Thyroidectomy is the most frequent procedure in endocrine surgery. The conventional approach through a collar incision, as described by Kocher in XIX^th century, has become the “gold standard”. It is continuously evolving in spite of, many years ago, it showed to be safe and efficient with quality standards difficult to beat.Endoscopic and robotic surgery have developed “new approaches” to thyroid in order to improve the cosmetic results, looking even for invisible scars.We have done a thoughtful review of most of them trying to understand their benefits and drawbacks.Currently none of these “new approaches” have been shown to be better than conventional open thyroidectomy beyond offering a better cosmetic result. Besides, only a small percentage of patients can benefit of them. However, most of these approaches will remain if they treat the diseased thyroid and also improve the quality of life of our patients.     

Cytomegalovirus DNAemia and risk of mortality in allogeneic hematopoietic stem cell transplantation: Analysis from the Spanish Hematopoietic Transplantation and Cell Therapy Group

The net impact of cytomegalovirus (CMV) DNAemia on overall mortality (OM) and nonrelapse mortality (NRM) following allogeneic hematopoietic stem cell transplantation (allo-HSCT) remains a matter of debate. This was a retrospective, multicenter, noninterventional study finally including 749 patients. CMV DNA monitoring was conducted by real-time polymerase chain reaction (PCR) assays. Clinical outcomes of interest were OM and NRM through day 365 after allo-HSCT. The cumulative incidence of CMV DNAemia in this cohort was 52.6%. A total of 306 out of 382 patients with CMV DNAemia received preemptive antiviral therapy (PET). PET use for CMV DNAemia, but not the occurrence of CMV DNAemia, taken as a qualitative variable, was associated with increased OM and NRM in univariate but not in adjusted models. A subcohort analysis including patients monitored by the COBAS Ampliprep/COBAS Taqman CMV Test showed that OM and NRM were comparable in patients in whom either low or high plasma CMV DNA threshold (<500 vs ≥500 IU/mL) was used for PET initiation. In conclusion, CMV DNAemia was not associated with increased OM and NRM in allo-HSCT recipients. The potential impact of PET use on mortality was not proven but merits further research.