Neonatal Sepsis: Clinical characteristics, Epidemiology and Antibiotic Sensitivity Pattern of the Bacterial Pathogens in Neonatal Intensive Care Unit of a Tertiary Care Hospital.

Neonatal sepsis, a major newborn killer worldwide exhibits wide spectrum of clinical manifestations. Epidemiology and aetiological organisms vary with geographical area and time. Objective of the study was to study clinical characteristics, epidemiology, bacterial aetiology and drug sensitivity pattern of isolated organisms in Neonatal Intensive Care Unit (NICU), Dhaka Medical College Hospital (DMCH), Dhaka, Bangladesh. This observational cross sectional study was carried out in NICU, DMCH from January 2014 to June 2015. The inclusion criteria were newborns having features of sepsis at admission or developing such features afterwards when admitted for other indications. A blood sample was collected aseptically immediately after clinical diagnosis and was sent for relevant laboratory investigations. Sample for culture sensitivity was inoculated bedside to culture bottle and sent to department of microbiology. The newborns were followed up till hospital discharge or death. All information regarding history, laboratory findings and follow up were recorded in a structured questionnaire. Of the 200 neonates, 59% were diagnosed as having late onset sepsis (LONS). Premature and low birth weight (LBW) babies mostly suffered from LONS. Respiratory distress, tachycardia, lethargy were the predominant symptoms in both early and late sepsis. Blood culture yielded growth in 55% of the septic newborns. Klebsiella pneumoniae was the predominant organism in both early and late sepsis. Most of the Gram negative bacteria were sensitive to colistin, meropenem and imipenem. Case fatality was 24.39% and 34.74% in early and late sepsis respectively.

Pulmonary Arterio-Venous Malformation (PAVM): A Rare Case Report.

A 6-year-old boy from Comilla, was admitted in Dhaka Medical College Hospital with exertional dyspnea, central cyanosis, clubbing and was finally diagnosed as pulmonary Arterio-Venous Malformation (PAVM) by bubble contrast echocardiography, and pulmonary CT angiography. As PAVM is rare in children, it is often not thought of in differential diagnoses and the diagnosis remains in disguise. In this report, we described the clinical presentation of 6-year-old child with PAVM and also how to investigate the case to get the diagnosis.

T3 Regulates a Human Macrophage-Derived TSH-ß Splice Variant: Implications for Human Bone Biology.

TSH and thyroid hormones (T3 and T4) are intimately involved in bone biology. We have previously reported the presence of a murine TSH-ß splice variant (TSH-ßv) expressed specifically in bone marrow-derived macrophages and that exerted an osteoprotective effect by inducing osteoblastogenesis. To extend this observation and its relevance to human bone biology, we set out to identify and characterize a TSH-ß variant in human macrophages. Real-time PCR analyses using human TSH-ß-specific primers identified a 364-bp product in macrophages, bone marrow, and peripheral blood mononuclear cells that was sequence verified and was homologous to a human TSH-ßv previously reported. We then examined TSH-ßv regulation using the THP-1 human monocyte cell line matured into macrophages. After 4 days, 46.1% of the THP-1 cells expressed the macrophage markers CD-14 and macrophage colony-stimulating factor and exhibited typical morphological characteristics of macrophages. Real-time PCR analyses of these cells treated in a dose-dependent manner with T3 showed a 14-fold induction of human TSH-ßv mRNA and variant protein. Furthermore, these human TSH-ßv-positive cells, induced by T3 exposure, had categorized into both M1 and M2 macrophage phenotypes as evidenced by the expression of macrophage colony-stimulating factor for M1 and CCL-22 for M2. These data indicate that in hyperthyroidism, bone marrow resident macrophages have the potential to exert enhanced osteoprotective effects by oversecreting human TSH-ßv, which may exert its local osteoprotective role via osteoblast and osteoclast TSH receptors.

Graves' Disease Mechanisms: The Role of Stimulating, Blocking, and Cleavage Region TSH Receptor Antibodies.

The immunologic processes involved in Graves' disease (GD) have one unique characteristic--the autoantibodies to the TSH receptor (TSHR)--which have both linear and conformational epitopes. Three types of TSHR antibodies (stimulating, blocking, and cleavage) with different functional capabilities have been described in GD patients, which induce different signaling effects varying from thyroid cell proliferation to thyroid cell death. The establishment of animal models of GD by TSHR antibody transfer or by immunization with TSHR antigen has confirmed its pathogenic role and, therefore, GD is the result of a breakdown in TSHR tolerance. Here we review some of the characteristics of TSHR antibodies with a special emphasis on new developments in our understanding of what were previously called "neutral" antibodies and which we now characterize as autoantibodies to the "cleavage" region of the TSHR ectodomain.

Thyroid and bone: macrophage-derived TSH-ß splice variant increases murine osteoblastogenesis.

It is now firmly established that TSH may influence the physiology and patho-physiology of bone by activating osteoblasts and inhibiting osteoclast activity resulting in relative osteoprotection. Whether this influence is directly exerted by pituitary-derived TSH in vivo is less certain, because we have previously reported that the suppression of pituitary TSH does not remove such protection. Here, we have characterized the functional relevance of a novel form of the TSH-ß subunit, designated TSH-ßv, known to be produced by murine bone marrow cells. We found that fresh bone marrow-derived macrophages (MØs) preferentially produced TSH-ßv and, when cocultured with CHO cells engineered to overexpress the full-length TSH receptor, were able to generate the production of intracellular cAMP; a phenomenon not seen in control CHO cells, such results confirmed the bioactivity of the TSH variant. Furthermore, cocultures of MØs and osteoblasts were shown to enhance osteoblastogenesis, and this phenomenon was markedly reduced by antibody to TSH-ß, suggesting direct interaction between MØs and osteoblasts as observed under the electron microscope. These data suggest a new paradigm of local modulation of bone biology by a MØ-derived TSH-like molecule and raise the question of the relative contribution of local vs pituitary-derived TSH in osteoprotection.

Are extreme distal periprosthetic supracondylar fractures of the femur too distal to fix using a lateral locked plate?

It is unclear whether there is a limit to the amount of distal bone required to support fixation of supracondylar periprosthetic femoral fractures. This retrospective multicentre study evaluated lateral locked plating of periprosthetic supracondylar femoral fractures and compared the results according to extension of the fracture distal with the proximal border of the femoral prosthetic component. Between 1999 and 2008, 89 patients underwent lateral locked plating of a supracondylar periprosthetic femoral fracture, of whom 61 patients with a mean age of 72 years (42 to 96) comprising 53 women, were available after a minimum follow-up of six months or until fracture healing. Patients were grouped into those with fractures located proximally (28) and those with fractures that extended distal to the proximal border of the femoral component (33). Delayed healing and nonunion occurred respectively in five (18%) and three (11%) of more proximal fractures, and in two (6%) and five (15%) of the fractures with distal extension (p = 0.23 for delayed healing; p = 0.72 for nonunion, Fisher's exact test). Four construct failures (14%) occurred in more proximal fractures, and three (9%) in fractures with distal extension (p = 0.51). Of the two deep infections that occurred in each group, one resolved after surgical debridement and antibiotics, and one progressed to a nonunion. Extreme distal periprosthetic supracondylar fractures of the femur are not a contra-indication to lateral locked plating. These fractures can be managed with internal fixation, with predictable results, similar to those seen in more proximal fractures.

Pulse propagation and electron acceleration in a corrugated plasma channel.

A preformed plasma channel provides a guiding structure for laser pulses unbound by the intensity thresholds of standard waveguides. The recently realized corrugated plasma channel [Layer, Phys. Rev. Lett. 99, 035001 (2007)] allows for the guiding of laser pulses with subluminal spatial harmonics. These spatial harmonics can be phase matched to high energy electrons, making the corrugated plasma channel ideal for the acceleration of electrons. We present a simple analytic model of pulse propagation in a corrugated plasma channel and examine the laser-electron beam interaction. Simulations show accelerating gradients of several hundred MeV/cm for laser powers much lower than required by standard laser wakefield schemes.

Possible link between glycolysis and apoptosis induced by sodium fluoride.

Fluoride has been used to prevent caries in the dentition, but the possible underlying mechanisms of cytotoxicity induction by this compound are still unclear. Since fluoride is known as an inhibitor of glycolytic enzymes, we investigated the possible connection between NaF-induced apoptosis and glycolysis in human promyelocytic leukemia HL-60 cells. NaF-induced apoptotic cell death is characterized by caspase activation, internucleosomal DNA fragmentation, loss of mitochondrial membrane potential, and production of apoptotic bodies. Higher activation of caspases-3 and -9, as compared with that of caspase-8, suggested the involvement of an extrinsic pathway. Utilization of glucose was nearly halted by NaF, whereas that of glutamine was rather enhanced. NaF enhanced the expression of Bad protein, but not that of Bcl-2 and Bax proteins, and reduced HIF-1alpha mRNA expression. Analysis of these data suggests a possible link between glycolysis and apoptosis.

Antibodies against neural, nuclear, cytoskeletal, and streptococcal epitopes in children and adults with Tourette's syndrome, Sydenham's chorea, and autoimmune disorders.

BACKGROUND: Some cases of Tourette's syndrome (TS) are hypothesized to be caused by autoantibodies that develop in response to a preceding group A beta hemolytic streptococcal infection. METHODS: To test this hypothesis, we looked for the presence ot total and IgG antibodies against neural, nuclear, cytoskeletal and streptococcal epitopes using indirect immunofluorescent assays and Western blot techniques in three patient groups: TS (n = 81), SC (n = 27), and a group of autoimmune disorders (n = 52) and in normal controls (n = 67). Subjects were ranked after titrations of autoantibodies from 0 to 227 according to their level of immunoreactivity. RESULTS: TS patients had a significantly higher mean rank for total antineural and antinuclear antibodies, as well as antistreptolysin O titers. However, among children and adolescents, only the total antinuclear antibodies were increased in TS patients compared to age matched controls. Compared to SC patients, TS patients had a significantly lower mean rank for total and IgG class antineural antibodies, significantly lower IgG class anticytoskeletal antibodies, and a significantly higher rank for total antinuclear antibodies. Compared to a mixed group of autoimmune disorders, the TS patients had a significantly lower mean rank for total and IgG class antineural antibodies, total and IgG class antinuclear antibodies, IgG class anticytoskeletal antibodies, and a significantly higher rank for antistreptococcal antibodies. CONCLUSIONS: TS patients had significantly higher levels of total antineural and antinuclear antibodies than did controls. Their relation to IgG class antineural and antinuclear antibodies, markers for prior streptococcal infection, and other clinical characteristics, especially chronological age, was equivocal.

Intensive generation of NK1.1- extrathymic T cells in the liver by injection of bone marrow cells isolated from mice with a mutation of polymorphic major histocompatibility complex antigens.

Whether intermediate TCR (TCRint) cells and natural killer T (NKT or NK1.1+TCRint) cells are extrathymically generated remains controversial. This arises from the fact that there are few of these T cells in athymic nude mice and neonatally thymectomized mice. However, when athymic mice were provided with appropriate microenvironments or stimulation, many TCRint cells (mainly NK1.1-) were found to arise in the liver. NKT cells are known to be positively selected by monomorphic major histocompatibility complex (MHC) -like antigens (e.g. CD1d). This is true even if they are CD4+. In other words, a MHC class I-like antigen is restricted to CD4 antigen. This rule is somewhat different from that seen in conventional T cells (i.e. the restriction of class II with CD4 and that of class I and CD8). In the case of NK1.1-TCRint cells, they were selected by polymorphic MHC antigens, but their MHC restriction to CD4 or CD8 antigen was incomplete. This was revealed by experiments of bone marrow transfer with class I (bm 1) or II (bm 12) disparity. Depending on the disparity, a unique cytokine profile in sera was detected. These results suggest that the development of T lineage lymphocytes and MHC restriction to CD4 and CD8 might have occurred in parallell as a phylogenic event, and that NK1.1- extrathymic T cells (i.e. NK1.1-TCRint) are at an intermediate position between NKT cells and conventional T cells in phylogeny.

The question of PANDAS in adults.

BACKGROUND: Pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections (PANDAS) are a well-defined cause of obsessive-compulsive disorder in children. However, they have not been described or fully investigated in adults newly diagnosed with obsessive-compulsive disorder. METHODS: We describe an adult with onset of obsessive-compulsive disorder at 25 years of age after a severe antibiotic-responsive pharyngitis. He was evaluated with multiple psychiatric rating scales for obsessive-compulsive disorder and Tourette's syndrome, as well as with serologic assays and radiologic studies. RESULTS: In all respects except age our patient fulfilled established criteria for PANDAS. Assays for antibodies to group A beta-hematolytic streptococci, serum D8,17 lymphocytes, antistriatal (neuronal) antibodies, and anticytoskeletal antibodies all supported the hypothesis that a poststreptococcal process was active. Magnetic resonance imaging was abnormal and is described. CONCLUSIONS: The findings suggest that this patient's illness is similar to PANDAS in presentation and that poststreptococcal disease may result in adult-onset obsessive-compulsive disorder.

Association of intermediate T cell receptor cells, mainly their NK1.1(-) subset, with protection from malaria.

Mice were infected with Plasmodium (P.) yoelii blood-stage parasites. Both the liver and spleen were the sites of inflammation during malarial infection at the beginning of day 7. The major expanding cells were found to be NK1.1(-) intermediate alphabetaTCR (alphabetaTCR(int)) in the liver and spleen, although the population of NK1.1(+) alphabetaTCR(int) cells remained constant or slightly increased. These TCR(int) cells are of extrathymic origin or are generated by an alternative intrathymic pathway and are distinguished from conventional T cells of thymic origin. During malarial infection, the population of conventional T cells did not increase at all. TCR(int) cells purified from the liver of mice which had recovered from P. yoelii infection protected mice from malaria when they were transferred into 6.5-Gy-irradiated mice. Interestingly, the immunity against malaria seemed to disappear as a function of time after recovery, namely, mice which had recovered from malaria 1 year previously again became susceptible to malarial infection. The present results suggest that TCR(int) cells are intimately associated with protection against malarial infection and, therefore, that mice which had recovered from malaria 1 year previously lost such immunity.

Endoscopic papillary dilation by balloon and isosorbide dinitrate drip infusion for removing bile duct stone.

BACKGROUND: Endoscopic papillary dilation (EPD) by balloon in the management of bile duct stones has recently been claimed to be effective for removing bile duct stones. METHODS: Without endoscopic sphincterotomy, we attempted to remove large or multiple bile duct stones through EPD combined with drip infusion of isosorbide dinitrate in 35 patients. Isosorbide dinitrate, at a rate of 5 mg/h, was administered intravenously, and a balloon dilator with a 10-mm diameter was inflated within 3 min across the papilla. Stones were then smashed using a mechanical lithotriptor, and the fragments were extracted with a basket or the balloon. RESULTS: Extraction of stones was successful in 33 (94%) of 35 patients by the combined therapy. Two of them (6%) developed mild pancreatitis. CONCLUSION: EPD combined with medical sphincter dilation was effective for large and multiple bile duct stones.

Antibodies to Ro/La, Cenp-B, and snRNPs antigens in autoimmune hepatitis of North America versus Asia: patterns of immunofluorescence, ELISA reactivities, and HLA association.

To assess whether demography is one of the important factors determining antibody response to nuclear antigens [ANA: SSA-Ro (52K and 60K), SSB-La, snRNPs (A, 70K, B'/B), and Cenp-B], we investigated 95 and 47 sera of autoimmune hepatitis (AIH) from North America and Asia, respectively, by immunofluorescent (IF) and recombinant ELISA. Correlations among nuclear IF patterns, ELISA, and disease indices were analyzed. The frequency and titer of individual antibodies differed significantly between the groups. Patients with speckled patterns were younger in both regions and had higher aspartate aminotransferase levels only in North America. HLA-A1, B8, DQ2, and DR4 or DR3 or both in North America, and A2, B61, DQ7, and DR4 in Asia were predominant. In Asia, B61 correlated with anti-70K, and DQ7 correlated with antibodies to 52K, Cenp-B, and B'/B. In North America, A1, B8, DR3 haplotype, and DQ2 correlated with antibodies to A and 70K. Anti-B'/B and DR4 in North America, and A2 in Asia, were associated with concurrent immunologic disorder. Individual ANA clusters correlated with individual HLA in the demography, and different HLA alleles might determine disease expression as well as different ANA being produced in AIH.

Endoscopic lithotomy of common bile duct stones with sublingual nitroglycerin and guidewire.

OBJECTIVE: In 21 patients, our objective was the endoscopic removal of common bile duct stones by sphincter dilation with the application of sublingual nitroglycerin. METHODS: Nitroglycerin 0.3-0.6 mg was needed for proper dilation of the orifice and for successful cannulation of the Dormia basket into the bile duct. Cannulation of the Dormia basket was simplified by placing the guidewire in the common bile duct beforehand. Because of possible stone impaction, a mechanical lithotriptor was applied smoothly in two patients. RESULTS: Complete stone removal was successful in 18 of the 21 (86%) patients. One patient who developed a mild form of acute pancreatitis recovered in a few days by conservative management with drip infusion of protease inhibitor. Blood pressure dropped transiently in a patient receiving nitroglycerin, but the general condition of the patient was stable. CONCLUSIONS: This procedure was found to be safe, easy, and effective in extracting common bile duct stones.

Antibodies to single-stranded and double-stranded DNA in antinuclear antibody-positive type 1-autoimmune hepatitis.

To determine the significance of antibodies to single-stranded (anti-ssDNA) and double-stranded DNA (anti-dsDNA) in antinuclear antibody (ANA)-positive type 1 autoimmune hepatitis, sera from 53 patients were tested by enzyme immunosorbent assay (ELISA) and indirect immunofluorescence using the Crithidia luciliae substrate. Anti-dsDNA were detected in 18 patients (34%) by ELISA and 12 patients (23%) by the Crithidia-based assay. Twenty patients with anti-dsDNA by either assay (38%) had higher serum levels of immunoglobulin G (3971 +/- 270 mg/dL vs. 3201 +/- 247 mg/dL, P = .05) than seronegative patients. They also had human leukocyte antigen (HLA) DR4 more commonly than other patients (83% vs. 41%, P = .006) and normal subjects (83% vs. 30%, P = .00007). In contrast to patients seropositive by the Crithidia-based assay, those seropositive by ELISA failed corticosteroid therapy more commonly (24% vs. 3%, P = .04). Anti-ssDNA were found in 45 patients (85%) and they did not distinguish patients with different clinical features or outcomes. We conclude that anti-dsDNA are common in ANA-positive type 1 autoimmune hepatitis. HLA DR4 is associated with their production, and seropositivity by ELISA characterizes patients who have a poorer immediate response to corticosteroid treatment. Anti-ssDNA are common but they do not have important clinical implications.

Viral hepatitis in Japan: update.

Viral hepatitis is defined as a hepatitis virus infection in which hepatic inflammation and necrosis lead to a characteristic feature. It is caused by at least five viral agents with specific epidemiological attributes and distinctive immunoserologic findings. The well-characterized forms are hepatitis A, B, C, D and E viruses. Recent status and the current progress of viral hepatitis in Japan are discussed in the present article.

Frequency and significance of antibodies to P450IID6 protein in Japanese patients with chronic hepatitis C.

BACKGROUND/AIMS: The aims of the current study were to assess the frequency and the significance of antibodies to cytochrome P450IID6 protein (anti-P450IID6) in various diseases among Japanese patients. METHODS: Sera from 541 patients were tested by indirect immunofluorescence, and the specificity of anti-P450IID6 was ascertained by either enzyme immunoassay (ELISA) or Western blot using recombinant antigen or rat liver microsomes. RESULTS: Anti-P450IID6 was found in only 6 of 235 patients (2.6%) with chronic active hepatitis (CAH) positive for hepatitis C virus (HCV) antibody and quantitative HCV-RNA with genotypes II and IV. The predominant epitopes on immunoblots were 66 and 50KD, a 10KD band being the newly underfined microsomal antigen. Even in the patients negative for autoantibodies to nuclear antigens (ANA) by routine indirect immunofluorescence test, various ANA were detected by the newly developed recombinant ELISA. These patients were younger, with lower gamma-globulin and IgG levels than patients with autoimmune hepatitis. Three of five patients with anti-P450IID6 responded well to interferon therapy and one received prednisone when interferon was ineffective. Interestingly, only this patient was diagnosed as definite autoimmune hepatitis according to the criteria proposed by the International Autoimmune Hepatitis Group (IAHG). The other five patients who did not satisfy the IAHG criteria might be considered as CAH-C with autoimmune features. No autoimmune hepatitis patients positive for anti-P450IID6 were identified in the current study, indicating that the variant is very rare in Japan. CONCLUSIONS: Anti-P450IID6 in CAH-C patients in Japan is not as rare as expected. Anti-P450IID6 among Japanese patients has uncertain significance and precludes further characterization of CAH-C with autoimmune features, which might require interferon therapy.