T‐705‐modified ssRNA in complex with Lassa virus nucleoprotein exhibits nucleotide splaying and increased water influx into the RNA‐binding pocket

Lassa virus infection is clinically characterized by multiorgan failure in humans. Without an FDA‐approved vaccine, ribavirin is the frontline drug for the treatment but with attendant toxicities. 6‐Fluoro‐3‐hydroxy‐2‐pyrazinecarboxamide (T‐705) is an emerging alternative drug with proven anti‐Lassa virus activity in experimental model. One of the mechanisms of action is its incorporation into nascent single‐strand RNA (ssRNA) which forms complex with Lassa nucleoprotein (LASV‐NP). Here, using molecular dynamics simulation, the structural and electrostatics changes associated with LASV‐NP‐ssRNA complex have been studied when none, one, or four of its bases has been substituted with T‐705. The results demonstrated that glycosidic torsion angle χ (O4′‐C1′‐N1‐C2) rotated from high‐anti‐ (?110° and ?60°) to the syn‐ conformation (+30) with increased T‐705 substitution. Similarly, increased T‐705 substitution resulted in increased splaying (55°–70°), loss of ssRNA‐LASV‐NP H‐bond interaction, increased water influx into the ssRNA‐binding pocket, and decreased electrostatic potentials of ssRNA pocket. Furthermore, strong positively correlated motion observed between α6 residues (aa: 128–145) and its contact ssRNA bases (5–7) is weakened in Apo biosystem and transitioned into anticorrelated motions in ssRNA‐bound LASV‐NP biosystem. Finally, LASV genome may become more accessible to cellular ribonuclease access with T‐705 incorporation due to loss of NP interaction.     

Natural history and long-term follow-up of antenatally detected liver cysts

Background/Purpose

Antenatally detected liver cysts are rare; their diagnostic accuracy is unknown, and their management is controversial. This study assessed the natural history of these lesions.

Methods

We conducted a retrospective review of infants with isolated intrahepatic cysts that were detected antenatally. Data are expressed as median (range).

Results

Fifteen infants presented during the period 1991-2004 with an antenatally detected liver cyst. Their gestational age at detection was 22 (18-34) weeks, and the maximum diameter of their cyst was 23 (10-120) mm. Serial scans, which were performed in 9 fetuses, showed cyst enlargement in 5 cases, diminution in 1 case, and no change in 3 cases. In utero percutaneous aspiration was required in 1 infant. Three infants underwent postnatal surgery. One fetus (postfetal intervention) had a subtotal excision of a large subcapsular cyst filling the abdominal cavity on day 2. Another infant required partial excision and marsupialization (complex cyst arising from segment IV) at 5 months, and a third infant underwent a cyst cholecystostomy at 4 months. Postnatal investigations (including hepatic scintigraphy) suggested that the remaining lesions were either simple parenchymal (n = 10) or isolated intrahepatic choledochal (ie, type V; n = 2) cysts. The median follow-up for these patients was 44 (27-167) months. Serial postnatal ultrasonography showed cyst diminution in 4 cases, an enlargement in 1 case, and no dimensional change in 7 cases.

Conclusions

Most antenatally detected liver cysts appear to be simple and of parenchymal origin and do not require fetal intervention. Their postnatal history is variable, but regression without treatment is seen in most cases.     

Traumatic pancreatic duct injury in children: minimally invasive approach to management

Background

The management of children with main pancreatic duct injuries is controversial. We report a series of patients with pancreatic trauma who were treated using minimally invasive techniques.

Methods

Retrospective review of children with pancreatic trauma treated at a UK tertiary referral institution between 1999 and 2004.

Results

Fifteen children (11 boys) were admitted with pancreatic trauma. Twelve (80%) were less than 50th centile for body weight. Contrast-enhanced computed tomography (CT) scans were used to define organ injury, supplemented by magnetic resonance cholangiopancreatography (MRCP) in 7. Twelve (80%) underwent diagnostic endoscopic retrograde cholangiopancreatography (ERCP) with a median time after injury of 11 (range, 6-29) days. The degree of pancreatic injury was defined by ERCP and CT/MRCP as grade II (n = 2), grade III (n = 4), grade IV (n = 9) (American Association for the Surgery of Trauma grades). Nine children had a transductal pancreatic stent inserted endoscopically. Computed tomography/ultrasound-guided drainage was performed in 4 children for acute fluid collections. Two children later underwent endoscopic cyst-gastrostomy, one of whom later required conversion to an open cyst-gastrostomy.

Conclusion

Body habitus may predispose to pancreatic duct trauma. Contrast-enhanced CT scan (and MRCP) should dictate the need for ERCP. Transductal pancreatic stenting allows internal drainage of peripancreatic collections and may reestablish duct continuity, although a proportion still requires percutaneous or endoscopic cyst-gastrostomy drainage. Open surgery for pancreatic trauma should now be an exception.     

Response to HBV vaccine in relation to vaccine dose and anti-HCV positivity: a New South Wales correctional facilities' study.

Currently, about two-thirds of inmates in NSW correctional facilities have a history of injection drug use, and about half have serological evidence of exposure to hepatitis C virus. The introduction of an accelerated hepatitis B vaccination program (0-1-2 months) in 1998, using a 20 microg/dose vaccine was necessitated by the need to vaccinate eligible inmates in this high-risk environment characterised by rapid client mobility. Since 1999, both 10 and 20 microg doses of vaccine were introduced. We found that sero-response rates were not significantly influenced by HCV antibody status, but were significantly lower in cohorts of inmates vaccinated with the 10 microg dose of vaccine.