Modulation of potential respiratory pathogens by pH1N1 viral infection.

While much effort has been made to characterize influenza A pdm09 virus (pH1N1), the flu that was responsible for the fourth influenza pandemic, there is a lack of study on the composition of bacteria that lead to secondary infection. In this study, we recruited pneumonia patients with and without pH1N1 infection and characterized their oropharyngeal microbiota by the unbiased high-throughput sequencing method. While there were no significant differences in common bacterial pneumonia-causative agents (Acinetobacter and Streptococcus species), previously unreported Pseudomonas species equipped with chemotaxis and flagellar assembly genes significantly increased (>20-fold) in the pH1N1-infected group. Bacillus and Ralstonia species that also increased significantly (5-10-fold) were also found to possess similar signaling and motility genes. In contrast, no such genes were found in oral commensal Prevotella, Veillonella and Neisseria species, which decreased significantly, or in either Acinetobacter or 10 out of 21 Streptococcus species, including Streptococcus pneumoniae. Our results support the notion that pH1N1 infection provides a niche for previously unnoticed potential respiratory pathogens that were able to access the lower respiratory tract with weakened immunity.

Detection and identification of plasma bacterial and viral elements in HIV/AIDS patients in comparison to healthy adults.

A low level of CD4+ lymphocyte cells makes end-stage HIV/AIDS patients highly susceptible to microbial infections. We have adopted the next generation sequencing method to identify the spectrum of bacterial plasma and viral elements that might be present in these patients. The HIV/AIDS plasma microbiome was dominated by bacterial elements in the taxonomical order Pseudomonadales, while healthy people carried fewer bacterial DNA in the plasma. We have found that many of the bacterial elements in HIV/AIDS plasma are similar to those of the microbes found in the human gut, suggesting potential acquisition of microbial elements from the gut. The HIV/AIDS and normal plasma DNA virome shared some similarities in the presence of common ubiquitous eukaryotic viruses. The normal DNA virome was mainly composed of viruses from Anelloviridae. In contrast, the HIV/AIDS DNA virome contained a large proportion of bacteriophages, endogenous retroviruses and a non-human virus. In addition, several sequences, which might belong to novel bacteria or endogenous retroviruses, were identified. Taken together, the use of high-throughput sequencing technology in unveiling microbial metagenomics may facilitate future research in combating HIV/AIDS and its associated microbial complications.

Deletion of the CD4 silencer element supports a stochastic mechanism of thymocyte lineage commitment.

The mechanism of T cell lineage commitment remains controversial; to examine it we deleted the CD4-silencer element in the germ line of a mouse using a combination of gene targeting and Cre/LoxP-mediated recombination. We found that these mice were unable to extinguish CD4 expression either in immature thymocytes or mature CD8+ cytotoxic T cells (CTLs), which resulted in the development of major histocompatibility complex class II-restricted double-positive CTLs in the periphery. This finding strongly supports a stochastic over an instructive mechanism of coreceptor down-regulation.

In vitro effects of Trichinella spiralis on muscle cells.

Introduction of excretory/secretory (ES) products of both infective-stage and newborn larvae of Trichinella spiralis into cultures of primary rat myocytes elicited morphological and structural changes in the myotubes. They appeared more granular, thinner, and failed to form networks. The most prominent lesion was the formation of 'nodular' structures, each bearing an enlarged nucleus, along the myotubes. Each node contained numerous cavities enclosed by an intact sarcolemma. Co-culture of myocytes with newborn larvae also elicited nodular formation but each node contained a large central cavity encircled by smaller ones. An immunocytolocalization study using IFAT and laser confocal microscopy showed the presence of parasitic epitopes inside the nodes. However, ES products from adult worms did not affect the myotubes.

Production specific antigens from Trichinella spiralis using a continuous elution method and isoelectric focusing.

Immunodominant antigens of 45-53 kDa (one band per fraction) were obtained from excretory/secretory (E/S) and somatic products of infective-larvae of Trichinella spiralis using a continuous-elution method. They were further resolved by isoelectric focusing into different isoforms (45 kDa: pI4.47, 5.09, 5.47 and 5.86; 47 kDa: pI4.72 and 4.97; 53 kDa: pI4.86, 5.11, 5.44 and 5.78). In immunoblotting, the isoforms of pI 5.09, 5.86, 4.97, 5.44 and 5.78 did not cross-react with antisera against Trichuris suis, Metastrongylus apri, Gnathostoma hispidum and Stephanurus dentatus. Hence, they have the potential to serve as specific antigens for the serodiagnosis of trichinellosis.

Plasma catecholamines and neonatal condition after induction of anaesthesia with propofol or thiopentone at caesarean section.

Increased maternal sympathetic nervous system activity may decrease placental perfusion and cause adverse neonatal effects. We have studied the catecholamine response and neonatal outcome in Chinese patients with uncomplicated, singleton pregnancies undergoing Caesarean section. Anaesthesia was induced with thiopentone 4 mg kg-1 (n = 32) or propofol 2 mg kg-1 (n = 30) followed by suxamethonium. Laryngoscopy was performed after 1 min and tracheal intubation completed by 2 min. Anaesthesia was continued with atracurium, nitrous oxide and isoflurane. Maternal venous blood samples were taken at 0, 1, 2, 3, 4 min and at delivery for assay of catecholamines. The increase from baseline values in mean arterial pressure after tracheal intubation was greater in the thiopentone group (29 (SD 15) mm Hg) compared with the propofol group (18 (14) mm Hg) (P < 0.01). The concentrations of noradrenaline and adrenaline increased in both groups after tracheal intubation. Maximum noradrenaline concentrations were greater in the thiopentone group (413 (177) pg ml-1) compared with the propofol group (333 (108) pg ml-1) (P < 0.05), but there were no differences between groups in adrenaline concentrations. Neonatal Apgar scores, neurobehavioural testing and umbilical catecholamine, blood-gas tension and oxygen content analysis were similar between groups. Propofol attenuated the hypertensive and catecholamine response associated with laryngoscopy and tracheal intubation but there was no improvement in neonatal outcome.

Disposition of propofol at caesarean section and in the postpartum period.

We have compared the pharmacokinetics of a bolus dose of propofol 2 mg kg-1 in eight patients undergoing Caesarean section with those in eight postpartum patients undergoing sterilization by mini-laparotomy. The Caesarean section group had a total body clearance of (median) 31.5 (range 24.4-53.3) ml min-1 kg-1, apparent volume of distribution at steady state 5.10 (2.46-6.61) litre kg-1 and mean residence time 161 (52.3-251) min; values for the post-partum group were 33.8 (21.5-47.2) ml min-1 kg-1, 5.17 (3.47-8.09) litre kg-1 and 163 (92.3-238) min, respectively. The 95% confidence interval for the umbilical venous to maternal venous ratio of propofol at delivery was 0.62-0.86. Plasma protein binding studies showed there was less unbound propofol in maternal plasma (1.28-2.29%) compared with umbilical plasma (2.08-3.88%) (P less than 0.01). Neonatal concentrations of propofol were greater than maternal concentrations at 2 h and were in the range 0.05-0.11 micrograms ml-1 at 4 h.

Propofol for induction and maintenance of anaesthesia at caesarean section. A comparison with thiopentone/enflurane.

A propofol infusion regimen and a standard general anaesthetic were compared in 40 Chinese women undergoing elective Caesarean section. Twenty patients received propofol 2 mg/kg for induction of anaesthesia followed by propofol 6 mg/kg/hour, while 20 patients received thiopentone 4 mg/kg with enflurane 1% for maintenance of anaesthesia. All patients were given atracurium and their lungs ventilated with nitrous oxide 50% in oxygen until delivery of the neonate. The hypertensive response after intubation was of shorter duration in the propofol group compared with the thiopentone group. Induction to delivery times ranged from 5 to 14 minutes and neonates from both groups had similar and satisfactory Apgar scores. Neurologic and Adaptive Capacity Scores and umbilical cord blood gas analysis. However, a prolonged propofol infusion time before delivery may cause lower Neurologic and Adaptive Capacity Scores. There were no differences in maternal recovery times or psychomotor performance.

Propofol infusion anaesthesia for caesarean section.

Two propofol infusion regimens and a standard general anaesthetic were compared in thirty Chinese women undergoing elective Caesarean section. After induction of anaesthesia with propofol 2 mg.kg-1, ten patients received propofol 6 mg.kg-1.hr-1 and nitrous oxide 50 per cent in oxygen while ten were given propofol 9 mg.kg-1.hr-1 with 100 per cent oxygen. The other ten patients received thiopentone 4 mg.kg-1 and nitrous oxide 50 per cent in oxygen with enflurane one per cent. Maternal recovery times and psychomotor performance were recorded. Neonates were assessed by Apgar scores, neurologic and adapative capacity scores (NACS) and umbilical cord blood gas analysis. Haemodynamic changes were similar immediately following induction but the low propofol infusion group had the best haemodynamic stability subsequently. Recovery times were fastest in the low-infusion group but there were no differences in later postbox testing. Neonatal Apgar scores and umbilical blood gas analysis were similar but NACS at two hours were poorer in the high infusion group. A propofol infusion coupled with nitrous oxide appears to be a satisfactory technique for Caesarean section.

Late metabolic acidosis and poor weight gain in moderately pre-term babies fed with a casein-predominant formula: a continuing need for caution.

When our neonatal unit opened in 1984 our formula feeding policy for moderately preterm babies was for casein-predominant rather than "humanized" whey-predominant milk formulae to be given. However, an early cluster of cases of late persistent metabolic acidosis prompted an investigation into the acid-base status and weight gain in preterm infants. This study of 70 healthy, moderately preterm (32-35 weeks) Chinese babies has convincingly shown that a casein-predominant low protein formula is associated with significant metabolic acidosis, persisting sometimes for as long as 8 weeks, and poor weight gain when compared with infants fed on either a humanized or a special low-birthweight formula. This is an important message for the many neonatal units in developing countries where the cost of humanized formulae might initially seem prohibitive, encouraging instead casein-predominant formulae when breast milk is not available. Any additional expense incurred in using humanized formulae will be compensated for by the shortened time spent in hospital.

Mitral valve prolapse syndrome in children with Duchenne's progressive muscular dystrophy.

Myocardial function was evaluated prospectively by noninvasive methods in 20 boys with clinical, biochemical, muscle biopsy, and electromyographic evidence of Duchenne's progressive muscular dystrophy. Auscultatory evidence of a nonejection systolic click suggested mitral valve prolapse (MVP) syndrome in seven patients. Phonocardiography disclosed that the click was mid-systolic in four patients and early in three. Echocardiographic features consistent with this diagnosis were identified in all seven patients and in an additional four. One of these had an apical pansystolic murmur, suggestive of mitral regurgitation, whereas in the other three, prolapse of the mitral valve was "silent". Echocardiographic findings included an abrupt midsystolic, posterior motion (greater than 3 mm beyond the CD line) in five patients, multiple sequence echoes in six, and posterior coaptation of the mitral valve near the left atrial wall in six. The features most characteristic of MVP syndrome was a smooth, pansystolic, anteriorly concave (hammock-like) posterior motion deviating more than 3 mm beyond the CD line. Among the remaining nine patients who did not have echocardiographic evidence of prolapsing mitral valve, none had an early, middle or late nonejection systolic click or a heart murmur, although four patients in this group had moderate to severe scoliosis. These observations document of occurrence of MVP syndrome in children with Duchenne's muscular dystrophy and indicate that its prevalence is high. We speculate that prolapse of the mitral valve in these patients is an expression of the underlying cardiomyopathy characteristic of Duchenne's muscular dystrophy rather than an isolated, dystrophic involvement of the mitral valve leaflets.