Surveillance of active human cytomegalovirus infection in hematopoietic stem cell transplantation (HLA sibling identical donor): search for optimal cutoff value by real-time PCR

Background  

Human cytomegalovirus (CMV) infection still causes significant morbidity and mortality after allogeneic hematopoietic stem cell transplantation (HSCT). Therefore, it is extremely important to diagnosis and monitor active CMV infection in HSCT patients, defining the CMV DNA levels of virus replication that warrant intervention with antiviral agents in order to accurately prevent CMV disease and further related complications.     

CpG island methylation of TMS1/ASC and CASP8 genes in cervical cancer

Background

Gene silencing associated with aberrant methylation of promoter region CpG islands is an acquired epigenetic alteration that serves as an alternative to genetic defects in the inactivation of tumor suppressor and other genes in human cancers.

Aims

This study describes the methylation status of TMS1/ASC and CASP8 genes in cervical cancer. We also examined the prevalence of TMS1/ASC and CASP8 genes methylation in cervical cancer tissue and none - neo plastic samples in an effort to correlate with smoking habit and clinicopathological features.

Method

Target DNA was modified by sodium bisulfite, converting all unmethylated, but not methylated, cytosines to uracil, and subsequently amplified by Methylation Specific (MS) PCR with primers specific for methylated versus unmethylated DNA. The PCR product was detected by gel electrophoresis and combined with the clinical records of patients.

Results

The methylation pattern of the TMS1/ASC and CASP8 genes in specimens of cervical cancer and adjacent normal tissues were detected [5/80 (6.2%), 3/80 (3.75%)-2/80 (2.5%), 1/80 (1.2%) respectively]. No statistical differences were seen in the extent of differentiation, invasion, pathological type and smoking habit between the methylated and unmethylated tissues (P > 0.05).

Conclusion

The present study conclude that the frequency of TMS1/ASC and CASP8 genes methylation in cervical cancer are rare (< 6%), and have no any critical role in development of cervical cancer.     

Profile of culture positive enteric fever from bangalore

Background: Enteric fever is endemic in India. The aim of this study was to analyse the clinical, laboratory, antibiotic sensitivity profile and response to antibiotics of culture positive enteric fever patients from Bangalore.     

LASSBio-881: an N-acylhydrazone transient receptor potential vanilloid subfamily type 1 antagonist orally effective against the hypernociception induced by capsaicin or partial sciatic ligation

Background and purpose:

Compound LASSBio-881 is an orally effective antinociceptive that binds to cannabinoid receptors and is active mainly on the neurogenic component of pain models. We investigated whether transient receptor potential vanilloid subfamily type 1 (TRPV1) channels are involved in the effects of LASSBio-881.

Experimental approach:

Modulation of capsaicin (CAP)- and low pH-induced currents was evaluated in TRPV1-expressing Xenopus oocytes. In vivo effects were evaluated in CAP-induced acute and inflammatory changes in nociception, as well as in partial sciatic ligation-induced thermal hypernociception.

Key results:

LASSBio-881 inhibited TRPV1 currents elicited by CAP with an IC₅₀ of 14 µM, and inhibited proton-gated currents by 70% at 20 µM. Functional interaction with CAP was surmountable. Locally applied LASSBio-881 decreased time spent in CAP-elicited nocifensive behaviour by 30%, and given orally it reduced measures of CAP- or carrageenan-evoked thermal hypernociception by 60 and 40% respectively. In addition, LASSBio-881 decreased the paw withdrawal responses to thermal stimuli of animals with sciatic neuropathy 7–11 days after nerve ligation, at a dose of 300 µmol·kg⁻¹·day⁻¹ p.o. At this dose, hyperthermia was not observed within 4 h following oral administration.

Conclusions and implications:

LASSBio-881 is a TRPV1 antagonist that apparently competes with CAP. Accordingly, LASSBio-881 inhibited nociception in models of acute, inflammatory and neuropathic pain presumed to involve TRPV1 signalling. These in vivo actions were not hindered by hyperthermia, a common side effect of other TRPV1 antagonists. We propose that the antinociceptive properties of LASSBio-881 are due to TRPV1 antagonism, although other molecular interactions may contribute to the effects of this multi-target drug candidate.     

Non-Occlusive Small Bowel Necrosis in Association with Feeding Jejunostomy After Elective Upper Gastrointestinal Surgery

INTRODUCTION

Non-occlusive small bowel necrosis (NOSBN) has been associated with early postoperative enteral feeding. The purpose of this study was to determine the incidence of this complication in an elective upper gastrointestinal (GI) surgical patient population and the influence of both patient selection and type of feeding jejunostomy (FJ) inserted, based on the experience of two surgical units in affiliated hospitals.

PATIENTS AND METHODS

The records were reviewed of 524 consecutive patients who underwent elective upper GI operations with insertion of a FJ for benign or malignant disease between 1997 and 2006. One unit routinely inserted needle catheter jejunostomies (NCJ), whilst the other selectively inserted tube jejunostomies (TJ).

RESULTS

Six cases of NOSBN were identified over 120 months in 524 patients (1.15%), with no difference in incidence between routine NCJ (n = 5; 1.16%) and selective TJ (n = 1; 1.06%). Median rate of feeding at time of diagnosis was 105 ml/h (range, 75–125 ml/h), and diagnosis was made at a median of 6 days (range, 4–18 days) postoperatively. All patients developed abdominal distension, hypotension and tachycardia in the 24 h before re-exploratory laparotomy. Five patients died and one patient survived.

CONCLUSIONS

The understanding of the pathophysiology of NOSBN is still rudimentary; nevertheless, its 1% incidence in the present study does call into question its routine postoperative use especially in those at high risk with an open abdomen, planned repeat laparotomies or marked bowel oedema. Patients should be fully resuscitated before initiating any enteral feeding, and feeding should be interrupted if there is any evidence of feed intolerance.     

Effects of insulin-like growth factor I treatment on the molecular distribution of insulin-like growth factors among different binding proteins

The molecular distribution of insulin-like growth factor I (IGF-I) and IGF-II among the IGF binding proteins (IGFBPs) was studied before and during IGF-I therapy in Ecuadorean adults with growth hormone receptor deficiency (GHRD). Of the total circulating IGF-I and IGF-II, 70% was carried by the 150 kDa complex in normal subjects, while in patients with GHRD, 50% of serum IGF-I, but only 30–35% of serum IGF-II, was measured within the 150 kDa IGFBP-3 region. Administration of IGF-I altered the concentration of IGF-I and IGF-II, although the percentage of total IGF measured within each IGFBP region was not affected, as the increase in IGF-I and the decrease in IGF-II were proportional. Similarly, serum concentrations of IGFBP-3 and the acid-labile subunit, measured by radioimmunoassay, were unaltered. Thus, administration of IGF-I to patients with GHRD was unable to correct the aberrant distribution of IGFs among the IGFBPs.     

Impaired prenatal and postnatal growth in Dutch patients with phenylketonuria. The National PKU Steering Committee

OBJECTIVE: To assess whether physical growth is affected in early treated Dutch patients with phenylketonuria (PKU). METHODS: The birth weights of all 137 early detected patients with PKU born in the period from 1974 to 1988 in the Netherlands were compared with reference values. Height, head circumference, and weight were measured at the age at which treatment started (commonly about 2-3 weeks), at 6 months of age, and yearly from the child's first birthday up to the age of 10 years. These measurements were compared with reference values. RESULTS: The adjusted birth weight in patients with PKU was 141 g (95% confidence interval (CI) 66 to 216 g) less than Dutch reference values by Kloosterman and 103 g (95% CI 9 to 196 g) less compared with the birth weight of another reference group. At the age at which treatment started, z scores of patients for height by age were -0.23 (95% CI -0.44 to -0.02) and z scores for head circumference by the age were -0.25 (95% CI -0.44 to -0.06). From the age at which treatment started up to the age of 3 years z scores for height by age further decreased to -0.74 (95% confidence interval -0.93 to -0.56), after which no additional decrease occurred. In contrast, z scores for head circumference increased from -0.25 at the first visit to 0.08 (95% CI -0.14 to 0.30) at the age of 1 year, after which they remained close to zero. Weight by height was close to the expected centiles for all ages. CONCLUSION: Patients with PKU are growth retarded at birth and have smaller head circumferences than the normal population. In Dutch patients further growth retardation occurs in the first three years of life.     

Gene therapy for phenylketonuria

Classical phenylketonuria (PKU) is an autosomal recessive disorder caused by a deficiency of hepatic phenylalanine hydroxylase (PAH). Three different vector systems have been developed to examine the potential of somatic gene therapy for the treatment of PKU. Recombinant retroviral vectors and DNA/protein complexes can efficiently transduce PAH-deiicient hepatocytes in vitro, but their present phenylketonuria, retrovirus application is limited by their low transduction efficiency in vivo. In contrast, infusion of a recombinant adenoviral vector expressing the human PAH cDNA into the portal circulation of PAH-deficient mice restores 10-80% of normal hepatic PAH activity and completely normalizes serum phenylalanine levels. At present, this effect is transient and re-administration has no further effect. However, this result suggests that PKU can be completely corrected by somatic gene therapy as more persistent vectors are developed.