Rabies Virus Populations in Humans and Mice Show Minor Inter-Host Variability within Various Central Nervous System Regions and Peripheral Tissues

Rabies virus (RABV) has a broad host range and infects multiple cell types throughout the infection cycle. Next-generation sequencing (NGS) and minor variant analysis are powerful tools for studying virus populations within specific hosts and tissues, leading to novel insights into the mechanisms of host-switching and key factors for infecting specific cell types. In this study we investigated RABV populations and minor variants in both original (non-passaged) samples and in vitro-passaged isolates of various CNS regions (hippocampus, medulla oblongata and spinal cord) of a fatal human rabies case, and of multiple CNS and non-CNS tissues of experimentally infected mice. No differences in virus populations were detected between the human CNS regions, and only one non-synonymous single nucleotide polymorphism (SNP) was detected in the fifth in vitro passage of virus isolated from the spinal cord. However, the appearance of this SNP shows the importance of sequencing newly passaged virus stocks before further use. Similarly, we did not detect apparent differences in virus populations isolated from different CNS and non-CNS tissues of experimentally infected mice. Sequencing of viruses obtained from pharyngeal swab and salivary gland proved difficult, and we propose methods for improving sampling.     

Triophthalmia and facial clefting: a case report.

We describe a Libyan boy with an unusual phenotype of multiple congenital anomalies, including triophthalmia, dolichocephaly, porencephaly, cleft lip/palate, facial asymmetry, micrognathia, and VSD. The reported phenotype is likely to represent a new entity of non-chromosomal syndromic triophthalmia. Other possibilities are discussed.     

Pharmacokinetic study of rifampicin in biliary surgery

Following the oral administration of 600 mg rifampicin, the concentration of antibiotic in serum, bile of the gallbladder and choledochus, cholecystic wall, and hepatic tissue was determined with the agar diffusion method in 23 patients undergoing surgery for cholelithiasis. After 80-340 minutes the average rifampicin concentration was 6.4 microgram/ml in serum, 78.4 microgram/ml in the bile of the gallbladder, 91.6 microgram/ml in the bile of the choledochus, 4.0 microgram/g in the cholecystic wall, and 23.3 microgram/g in the hepatic tissue. After 24 hours the level was significantly reduced in the serum and hepatic tissue. The rifampicin level in the bile of the gallbladder was twelvefold, in the bile of the choledochus fourteenfold, in the cholecystic wall 61.1% and in the hepatic tissue 364% of the serum level. In general, the rifampicin concentration obtainable in the bile and hepatic tissue is sufficient against bacterial strains causing infections of the biliary duct, and for this reason rifampicin will play in the future an important role in the treatment of infections of the biliary duct.     

Control of the Total Artificial Heart: New Aspects in Human versus Animal Experience

Control strategies for total artificial heart application have generally been based on experience with healthy animals. Human patients in a bad state of health who have impaired organ functions and who are subjected to intensive care procedures can develop atypical hemodynamic behavior. In these patients, both unstable and hyperstable behavior of the vascular resistance were observed. Therefore, regulation of cardiac output (CO) by pressure parameters only was avoided and CO was adjusted to obtain an appropriate O2-utilization (O2U). Intending to keep the O2U within ranges of 20-25%, we obtained cardiac indexes between 3.3 and 4.4 L/m2/min (CO 6-8 L/min), which is higher than other cardiac indexes reported. A CO of 10.5 L/min was even necessary to obtain an O2U of 30% in a septic patient. This strategy caused a stable driving management and led to a rapid hemodynamic stabilization and general improvement of the patients' condition. Results indicate that it is also very important to monitor metabolic parameters for appropriate driver adjustment as well, especially in the early postoperative phase, and that O2-U is a sensitive and useful parameter for this purpose.