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Biomedical subjects

Anita Verma

Publications and source records attributed to Anita Verma.

14 recordsLinked to original sources

Neonatal herpes simplex virus infection presenting as acute liver failure: prevalent role of herpes simplex virus type I.

BACKGROUND: Acute liver failure (ALF) in neonates is rare but carries a high mortality without liver transplantation. Herpes simplex virus (HSV) is one of the microbes that more commonly causes ALF and is potentially treatable; hence, early diagnosis and treatment are important to avoid progression to liver failure. PATIENTS AND RESULTS: We have analysed retrospectively the case notes of 11 patients with HSV-induced ALF. A history of possible herpes infection was elicited in 5 parents, but HSV had not been suspected clinically. All patients were asymptomatic when discharged from postnatal units and were presented with nonspecific symptoms of poor feeding and lethargy within 2 weeks from birth. Seven of the 11 patients had HSV-1 infection, 4 HSV-2. Only 2 patients who received early treatment with intravenous acyclovir survived. CONCLUSIONS: HSV-related ALF in the neonatal period carries high morbidity and mortality and needs a high index of suspicion so that life-saving treatment can be started promptly. Both HSV-1 and HSV-2 can cause severe neonatal infection. It is important to recognise HSV infection in women of childbearing age and their sexual partners.

Acyclovir↗

Immunization issues before and after solid organ transplantation in children.

Solid-organ transplant recipients are at risk from various infectious diseases, many of which can be prevented by immunizations that could reduce morbidity and mortality. However, it is not uncommon for children requiring transplantation to have received inadequate or no immunizations pre-transplant. Every effort should be made to immunize transplant candidates early in the course of their disease according to recommended schedules prior to transplantation. It is also important to immunize their household contacts and healthcare workers. In this review, we summarize the major immunization issues for children undergoing transplantation, the data currently available on immunization safety and efficacy, and suggest immunization practices to reduce vaccine-preventable disease. There is a real need for a standardized approach to the administration and evaluation of immunizations in this group of patients.

Child↗

Risk factors for fungal infection in paediatric liver transplant recipients.

Fungal infection (FI) is a major and potentially fatal complication in liver transplantation (LT). Published experience of FI in paediatric LT is limited. We therefore reviewed case records of 79 children, aged between 0.16 and 16 yr, who underwent LT between 1997 and 1998 to document the incidence of, and identify risk factors for, FI. Sixty-eight pre-, peri- and post-LT variables were assessed in relation to FI by univariate and multivariate analyses. The major indications for LT were biliary atresia in 26 (33%) patients, fulminant hepatic failure in 16 (20%) and intrahepatic cholestasis in 11 (14%); eight patients required re-LT. Thirty-two (40.5%) children developed a FI within 1 yr of LT. The median time to FI was 42 days (range 1-342 days). Candida spp. caused 29 (90.7%) FIs; 21 (66%) of these were Candida albicans. Although FI was associated with increased mortality, most patients responded well to antifungal treatment. The variables independently associated with FI were pre-LT fungal colonization and pyrexia and, post-LT, bacterial infection, Epstein-Barr virus (EBV) infection and tacrolimus administration. Identifying risk factors for FI should contribute to the development of strategies for prophylaxis or preemptive therapy.

Adolescent↗

Hepatocyte transplantation for inherited factor VII deficiency.

Hepatocyte transplantation has been investigated in patients with liver-based metabolic disorders and acute liver failure. We report the first use of hepatocyte transplantation in two brothers with severe inherited coagulation factor VII deficiency. Patient 1 received a total of 1.09x10(9) cryopreserved hepatocytes, and patient received 2.18x10(9) fresh and cryopreserved hepatocytes through a Hickman line inserted in the inferior mesenteric vein. Infusion of isolated human hepatocytes improved the coagulation defect and markedly decreased the requirement for exogenous recombinant factor VII (rFVIIa) to approximately 20% of that before cell transplantation. In both patients, episodes of line sepsis were associated with an increase in rFVIIa requirement. Six months posthepatocyte transplantation, higher rFVIIa doses were required, suggesting loss of transplanted hepatocyte function. Because of increasing problems with venous access and long-term uncertainty of the efficacy of hepatocyte transplantation, orthotopic liver transplantation was performed successfully in both cases.

Adolescent↗

Disseminated neonatal herpes simplex virus (HSV) type 2 infection diagnosed by HSV DNA detection in blood and successfully managed by liver transplantation.

UNLABELLED: We report a case of neonatal herpes presenting with liver failure and disseminated coagulopathy which followed unrecognised maternal primary genital herpes and was diagnosed by herpes simplex virus DNA detection in blood by polymerase chain reaction 2 weeks after initiation of empiric intravenous aciclovir. The child underwent liver transplantation while receiving suppressive antiviral therapy and remains well after 10 months of follow-up. CONCLUSION: our case highlights potential pitfalls in the diagnosis of neonatal herpes and indicates a role for blood herpes simplex virus polymerase chain reaction as a sensitive diagnostic tool in disseminated infection. It is one of very few reports where liver transplantation has been successfully carried out in a neonate with herpes simplex virus-induced liver failure.

Adult↗

Immunization status in children.

OBJECTIVE: Recent studies and surveys are observing a declining trend of routine immunization coverage and fully immunized children in India are reported to be 38%. A rapid assessment technique was used on National Immunization Day (PPI) to assess the immunization status among children in the age group of 12-23 months covering urban, rural and slum areas in UT, Chandigarh. METHODS: The study covered 796 children in proportion of their distribution in urban, rural and slum areas. RESULTS: Evaluation recorded fully immunized children as 72.23%, partially immunized as 22.99% and unimmunized as 4.64%. Only 58.66% children in urban slums were fully immunized. The overall coverage for various vaccines was BCG: 93.09%, DPT1/OPV1: 93.97%, DPT2/OPV2: 90.57%, DPT3/OPV3: 85.92% and measles: 76%. No sex-wise difference was noticed in the study. CONCLUSION: Efforts must be made to strengthen routine immunization programme especially in the underprivileged groups and areas such as slum in cities so that target of universal coverage can be achieved as envisaged at national level.

Female↗

Analysis of subassemblies of pertussis toxin subunits in vivo and their interaction with the ptl transport apparatus.

Pertussis toxin (PT) has an AB(5) structure that is typical of many bacterial protein toxins; however, this toxin is more complex than many toxins since it is composed of five different subunit types, subunits S1 to S5. Little is known about how PT assembles in vivo and how and when it interacts with its secretion apparatus, known as the Ptl transporter. In order to better understand these events, we expressed subsets of the genes encoding the S1, S2, and/or S4 subunits of PT in strains of Bordetella pertussis that either did or did not produce the Ptl proteins. We found evidence to suggest that certain subassemblies of the toxin, including subassemblies consisting of the S1 subunit and incomplete forms of the B oligomer, can form in vivo, at least transiently. These results suggest that the B oligomer of the toxin does not need to completely form before interactions between the S1 subunit and B-oligomer subunits can occur in vivo. All subassemblies localized primarily to the membrane fraction of the cell. Moreover, we found that Ptl-mediated secretion occurs in a strain that produces S1 and an incomplete complement of B-oligomer subunits. These results indicate that subassemblies of the toxin consisting of the S1 subunit and a partial B oligomer can interact with the Ptl system.

Bacterial Proteins↗

Identification of two eukaryote-like serine/threonine kinases encoded by Chlamydia trachomatis serovar L2 and characterization of interacting partners of Pkn1.

Genome sequencing of C. trachomatis serovar D revealed the presence of three putative open reading frames (ORFs), CT145 (Pkn1), CT673 (Pkn5), and CT301 (PknD), encoding eukaryote-like serine/threonine kinases (Ser/Thr kinases). Two of these putative kinase genes, CT145 and CT301, were PCR amplified from serovar L2, cloned, and sequenced. Predicted translation products of the ORFs showed the presence of conserved kinase motifs at the N terminus of the proteins. CT145 and CT301 (encoding Pkn1 and PknD, respectively) were expressed in Escherichia coli as GST fusion proteins. In vitro kinase assays with Escherichia coli-derived glutathione S-transferase fusion proteins showed autophosphorylation of Pkn1 and PknD, indicating that they are functional kinases. Gene expression analysis of these kinase genes in Chlamydia by reverse transcriptase PCR indicated expression of these kinases at the early mid phase of the developmental cycle. Immunoprecipitated native chlamydial Pkn1 and PknD proteins also showed autophosphorylation in an in vitro kinase assay. Phosphoamino acid analysis by thin-layer chromatography confirmed that Pkn1 and PknD are phosphorylated on both serine and threonine residues. Interaction of Pkn1 and PknD with each other as well as interaction of Pkn1 with inclusion membrane protein G (IncG) was demonstrated by using a bacterial two-hybrid system. These interactions were further suggested by phosphorylation of the proteins in in vitro kinase assays. This report is the first description of the existence of functional Ser/Thr kinases in Chlamydia. The results of these findings should lead to a better understanding of how Chlamydia interact and interfere with host signaling pathways, since kinases represent potential mediators of the intimate host-pathogen interactions that are essential to the intracellular life cycle of Chlamydia.

Amino Acid Sequence↗

Effect of the synergist, piperonyl butoxide, on the development of deltamethrin resistance in yellow fever mosquito, Aedes aegypti L. (Diptera: Culicidae).

The larvae and adults of Aedes aegypti were tested for the potential to develop resistance to the synthetic pyrethroid, deltamethrin, alone or a combination of deltamethrin with the synergist, piperonyl butoxide (PBO). Although continuous larval selection for 40 generations resulted in 703-fold resistance, the resistance ratio in the adults was only 1.3. Similarly, adult selections with deltamethrin showed a resistance ratio of less than four after 40 generations, indicating differential response to deltamethrin selection in the two developmental stages of the insect. When the susceptible larvae were subjected to selection pressure of deltamethrin and PBO in the ratio of 1:5 for 20 generations, the speed of selection for deltamethrin resistance slowed down by 60%. The F24 larvae obtained from the strain selected with deltamethrin alone were further subjected to selection pressure with synergized deltamethrin, which resulted in 89% reversal in deltamethrin resistance in just one generation. However, long-term selection with the insecticide-synergist combination returned resistance close to original levels in 15 generations. The data indicate the involvement of cytochrome P450-dependent detoxification as the primary mechanism of development of resistance to deltamethrin in the larvae. Implications of the results on the management of larval and adult stages of Ae. aegypti are discussed.

Aedes↗

Non-viral infections of the liver.

The function and anatomy of the liver renders this organ peculiarly susceptible to bacterial and parasitic infections; fungal infections are increasingly recognised in the immunocompromised. As biochemical abnormalities of liver function can be non-specific, a high index of suspicion of liver or biliary infection is required. A need for prompt investigation is emphasised by the potentially rapid progression and poor prognosis of some bacterial and fungal infections, and the public health implications of parasitic diseases. This review encompasses the major infections of the liver and biliary tree other than viral hepatitis and includes aspects of pathogenicity, epidemiology, clinical presentation, diagnosis and management.

Bacterial Infections↗

Neonatal damage of the ventral hippocampus impairs working memory in the rat.

We investigated if a developmental lesion of the ventral hippocampus, studied previously as an animal model of schizophrenia, impairs performance in working memory tests related to the prefrontal cortex. Adult rats with a neonatal or adult excitotoxic lesion of the ventral hippocampus were tested in a continuous delayed alternation and a discrete paired-trial variable-delay alternation task. Performance of rats with the neonatal lesion was impaired as compared with control rats on both tasks, whereas performance of rats with the adult lesion was not altered in either task. The pattern of impaired performance, that worsened with increasing delays in neonatally lesioned rats, resembled that reported previously in animals with adult lesions of the medial prefrontal cortex. These results indicate that an early developmental, but not adult hippocampal, insult impairs performance in tasks sensitive to the integrity of the prefrontal cortex, and suggest that working memory may be compromised by neonatal damage of the ventral hippocampus.

Animals↗

Activation of Rac, Cdc42 and other downstream signalling molecules by Bartonella bacilliformis during entry into human endothelial cells.

Bartonella bacilliformis is an intracellular bacterial pathogen of human endothelial cells. In vitro incubation of B. bacilliformis with human endothelial cells leads to the formation of filamentous actin extensions (filopodia) within 30 min, followed by formation of membrane rufflings or lamellipodia within 1 h of incubation. By immunofluorescence, F-actin phalloidin staining and anti-Rac antibodies were shown to co-localize in the membrane rufflings, indicating the recruitment of activated Rac at lamellipodia. Preincubation of endothelial cells with the Clostridial toxin, TcdB-10463, which inactivates the Rho-family GTPases, Rho, Rac and Cdc42, inhibited the entry of B. bacilliformis by 50-90%. Preincubation of endothelial cells with the Clostridial toxin, TcsL-1522, which specifically inactivates Rac and, to a lesser extent, Cdc42, but not Rho, inhibited entry by 30-40%. A 3.4-5.0-fold increase in activated (GTP-bound) -intracellular Rac and Cdc42 was observed in affinity precipitation assays. Increased kinase activity of p21-activated kinase (PAK), a specific downstream effector of activated Rac/Cdc42 was also observed during the time course of infection. Activation of SAPK/JNK-1 and 2, and p38 MAPKs in signalling pathways, was also detected during infection with Bartonella, as was increased binding activity of AP-1 transcription factor.

Actins↗