A case of purulent pneumococcal pericarditis

Background

Purulent bacterial pericarditis is a rare and potentially fatal disease. The course may be fulminant, and the presentation may pose a diagnostic challenge.

Internal Hernias: Clinical Findings,Management, and Outcomes in 49 Nonbariatric Cases

Internal hernia, the protrusion of a viscus through a peritoneal or mesenteric aperture, is a rare cause of small bowel obstruction. We report the clinical presentation, surgical management, and outcomes of one of the largest series of nonbariatric internal hernias. Ten-year retrospective review of patients at our institution yielded 49 cases of internal hernias. Majority of patients presented with symptoms of acute (75%) or intermittent (22%) small bowel obstruction. While 16% of CT scans were suspicious for internal hernia, in no cases the preoperative diagnosis of internal hernia was made. The most frequent internal hernias were transmesenteric (57.0%) and 34 hernias (69%) were caused by previous surgery. All internal hernias were reduced and the defects were repaired. Compromised bowel was present in 22 cases and 11 patients underwent small bowel resection. The mean postoperative hospitalization was 10.9 days. The overall mortality rate from our series is 2%, and the morbidity rate is 12%. Transmesenteric hernias, as complications of previous surgeries, are the most prevalent internal hernias. Preoperative diagnosis of internal hernia is extremely difficult because of the nonspecific clinical presentation. However, if discovered promptly, internal hernias can be repaired with acceptable morbidity and mortality. Poster presentation at Digestive Disease Week, May 22, 2006, Los Angeles, California, USA.     

Characterization of adhesive interactions between human endothelial cells and megakaryocytes.

Cell-cell adhesion is essential for many immunological functions and is believed to be important in the regulation of hematopoiesis. Adhesive interactions between human endothelial cells and megakaryocytes were characterized in vitro using the CMK megakaryocytic cell line as well as marrow megakaryocytes. Although there was no adhesion between unactivated human umbilical vein endothelial cells (HUVEC) and megakaryocytes, treatment of HUVEC with inflammatory cytokines such as IL-1 beta, tumor necrosis factor alpha, INF-gamma, or the phorbol ester phorbol myristate acetate (PMA) resulted in a time- and dose-dependent increase in adhesion. Stimulation of marrow megakaryocytes or CMK cells with the cytokines IL-1 beta, GM-CSF, IL-6, IL-3, or PMA augmented their adhesion to endothelium. Monoclonal antibodies against the LFA-1 subunit of the leukocyte adherence complex CD18 inhibited the binding of marrow megakaryocytes or CMK cells to HUVEC. Adhesion blocking experiments also demonstrated that the VLA-4/VCAM-1 pathway was important for megakaryocyte attachment to HUVEC. Adhesion promoted maturation of megakaryocytic cells as measured by increased expression of glycoproteins GpIb and GpIIb/IIIa and by increased DNA content. These observations suggest that alterations in megakaryocyte adhesion may occur during inflammatory conditions, mediated by certain cytokines, resulting in augmented megakaryocyte maturation.     

Psychiatric morbidity among people aged 85+ in 1987. A follow-up study at two and a half years: Associations with changes in psychiatric morbidity

This article reports findings from a longitudinal survey of very elderly people living at home in London. The research aimed to identify social, psychological and physical characteristics associated with positive ageing and successful survival in the community in later life and its converse—negative ageing—as well as the associated policy implications. Associations with psychiatric morbidity, measured using the General Health Questionnaire, among sample members without cognitive impairment between the baseline interviews in 1987 and at follow-up, two and a half years later in 1990, are reported. Twenty-five per cent of survivors scored over the threshold of the GHQ in 1987 and 30% scored over the threshold in 1990. Half of those with a score over the threshold in 1990 also scored over the threshold in 1987. Hierarchical regression (using residualized change analysis) was used to estimate the effects of the independent variables on changes in psychiatric morbidity. The most significant predictor of psychiatric morbidity (GHQ score) in 1990 was baseline GHQ score, followed by health and functional status scores. Health and functional status were also the strongest predictors of baseline (1987) GHQ scores. The uniqueness of the study lies in the collection of follow-up data on a sample of very elderly people, given that most surveys are corss-sectional and contain too few people aged 85+ to merit separate analysis. It contributes to the small body of literature on outcome of depression. The lack of consistent associations with recovery from psychiatric morbidity in the literature enhances the importance of studies aiming to identify factors associated with different outcomes.     

Safety and immunogenicity of Haemophilus type b-tetanus protein conjugate vaccine, mixed in the same syringe with diphtheria-tetanus-pertussis vaccine in young infants

As new vaccines are developed there is increasing interest in reducing the number of injections given to children by combining vaccines in one syringe. We studied the safety and immunogenicity of Haemophilus influenzae type b-tetanus protein conjugate vaccine (PRP-T) administered at ages 2, 4 and 6 months mixed in the same syringe with DTP vaccine and its effects on the seroresponse to DTP vaccine. A group of 112 healthy 2-month-old infants received DTP-PRP-T or DTP-placebo mixed immediately before immunization in the same syringe. The addition of PRP-T to DTP did not increase the rate of local or systemic reactions. After the first, second and third dose, the PRP-T recipients showed a geometric anti-PRP antibody mean of 0.13, 2.31 and 6.40 micrograms/ml vs. 0.07, 0.05 and 0.05 micrograms/ml among the DTP-placebo recipients, respectively. Of the PRP-T recipients, 94 and 98% attained antibody concentration of greater than or equal to 0.15 micrograms/ml protein after the second and third dose, respectively, and 65 and 94% attained a concentration of greater than or equal to 1.0 micrograms/ml after the second and third dose, respectively. At the age of 1 year 94 and 52% of the DTP-PRP-T recipients vs. 12% and 0% of the placebo recipients still maintained titers of greater than or equal to 0.15 and greater than or equal to 1.0 micrograms/ml, respectively. The administration of DTP in the same syringe with PRP-T did not affect significantly the antibody response to diphtheria and tetanus toxoid and to pertussis agglutinins. It is concluded that PRP-T vaccine could be administered in the same syringe as DTP.     

Characterization of RAFTK, a novel focal adhesion kinase, and its integrin-dependent phosphorylation and activation in megakaryocytes

We have recently isolated a cDNA encoding a novel human intracellular tyrosine kinase, termed RAFTK (for a related adhesion focal tyrosine kinase). The RAFTK cDNA, which encodes a polypeptide of 1,009 amino acids, shares 65% homology to the focal adhesion kinase (FAK), including several consensus motifs. In this report, we describe the biochemical characterization and functional analysis of the RAFTK protein. Coexpression of RAFTK and FAK proteins in megakaryocytic cells and blood platelets was observed. Using a specific antibody to RAFTK and the monoclonal antibody 2A7 to FAK, FAK and RAFTK could be distinguished antigenically. RAFTK had intrinsic tyrosine kinase and autokinase activities. It was phosphorylated on tyrosine in growing cultures of COS cells transfected with the pCDNAIII/flag-RAFTK expression vector containing the RAFTK cDNA ligated with the 8 amino acid flag peptide sequence. Similar to FAK, dephosphorylation of RAFTK was observed when adherent transfected COS cells were detached. Phosphorylation was regained upon replating of these cells on the fibronectincoated dishes. Analysis of tyrosine-phosphorylated RAFTK from adherent transfected COS cells showed that the Src homology 2 (SH2) domains of the Src and Fyn protein kinases as well as the Grb2 adaptor protein were able to specifically associate with RAFTK. Tyrosine phosphorylation of endogenous RAFTK was observed upon fibronectin-induced activation of human megakaryocytic cells. Furthermore, colocalization of RAFTK protein with vinculin, a focal adhesion protein, was observed by confocal microscopy in focal adhesion- like structures in adherent CMK cells and in transfected pCDNAIII/flag- RAFTK COS cells upon fibronectin activation. These data suggest that RAFTK is a novel member of the FAK family, that it localizes to focal adhesion-like structures in CMK megakaryocytic cells, that it participates in integrinmediated signaling pathways in megakaryocytes, and that it is able to associate with the tyrosine kinases Src and Fyn as well as the adaptor protein Grb2 via SH2-phosphotyrosine interactions.     

Animal models in the investigation of anorexia

Anorexia nervosa (AN) is an eating disorder of unknown origin that most commonly occurs in women and usually has its onset in adolescence. Patients with AN invariably have a disturbed body image and an intense fear of weight gain. There is currently no definitive treatment for this disease, which carries a 20% mortality over 20 years. Development of an appropriate animal model of AN has been difficult, as the etiology of this eating disorder likely involves a complex interaction between genetic, environmental, social, and cultural factors. In this review, we focus on several possible rodent models of AN. In our laboratory, we have developed and studied three different mouse models of AN based on clinical profiles of the disease; separation stress, activity, and diet restriction (DR). In addition, we discuss the spontaneous mouse mutation anx/anx and several mouse gene knockout models, which have resulted in an anorexic phenotype. We highlight what has been learned from each of these models and possibilities for future models. It is hoped that a combination of the study of such models, together with genetic and clinical studies in patients, will lead to more rational and successful prevention/treatment of this tragic, and often fatal, disease.