Plasma HIV-1 RNA decline within the first two weeks of treatment is comparable for nevirapine, efavirenz, or both drugs combined and is not predictive of long-term virologic efficacy: A 2NN substudy

BACKGROUND: The initial rate of plasma HIV-1 RNA (pVL) decline has been proposed as a marker of early efficacy of antiretroviral therapy (ART) and a possible predictor of late efficacy. We compared the rate of pVL decline in patients starting ART with nevirapine (NVP), efavirenz (EFV), or both drugs combined in addition to lamivudine (3TC) and stavudine (d4T). METHODS: Analysis of the viral decay constant (VDc) during the first 2 weeks of treatment in patients enrolled in the 2NN study who remained on allocated treatment. RESULTS: The median VDc (log10 copies per day, [interquartile range]) was similar for NVP (0.30 [0.25-0.36], EFV (0.31 [0.27-0.37]), and NVP + EFV (0.30 [0.27-0.36]). Patients with a baseline pVL >100,000 copies/mL were 8.7 (95% confidence interval [CI]: 6.2-12.3) times more likely to have a VDc >75th percentile. A high VDc was not associated with plasma drug concentration or with a decreased risk of virologic failure at week 48 after the start of therapy (hazard ratio = 0.8, 95% CI: 0.6-1.2). CONCLUSION: NVP, EFV, or NVP + EFV in combination with 3TC and d4T show similar rates of pVL decline during the first 2 weeks of treatment. The VDc with these regimens is not predictive of late virologic efficacy.     

Presentation of hepatitis B virus preS2 epitope on bluetongue virus core-like particles

A chimeric protein containing most of the hepatitis B virus preS₂ region (amino acid residues 1–48) upstream to, and colinear with the amino-terminus of bluetongue virus VP7 protein (preS₂VP7) was expressed by a recombinant Autographa californica nuclear polyhedrosis virus (AcNPV). The chimeric protein formed BTV core-like particles (CLPs) in Spodoptera frugiperda cells only when the cells were coinfected with this recombinant virus and a recombinant baculovirus that expresses unmodified VP7 and VP3 of BTV. The ratio of preS₂VP7 incorporated into CLPs was influenced by the relative multiplicities of infection of the two viruses. Immunoelectron microscopy of the chimeric particles indicated that the preS₂ epitope was exposed on the surface of the CLPs. When insect cells were coinfected with the preS₂ VP7 recombinant virus and a baculovirus vector that synthesized only the VP3 protein, no CLPs were identified.     

A modified single-loop reconstruction after pancreaticoduodenectomy reduces severity of postoperative pancreatic fistula in high-risk patients

Background

Double-loop (DL) reconstruction after pancreaticoduodenectomy (PD), diverting pancreatic from biliary secretions, has been reported to reduce rates and severity of postoperative pancreatic fistula (POPF) compared to single loop (SL) reconstruction at the price of prolonged operative duration. This study investigated the feasibility of a new reconstruction method combining the advantages of DL with the simplicity of SL in patients with high-risk pancreas.

A mechanistic approach for the calculation of intervertebral mobility in mammals based on vertebrae osteometry

In this paper, we develop and validate an osteometry-based mechanistic approach to calculation of available range of motion (aROM) in presacral intervertebral joints in sagittal bending (SB), lateral bending (LB), and axial rotation (AR). Our basic assumption was the existence of a mechanistic interrelation between the geometry of zygapophysial articular facets and aROM. Trigonometric formulae are developed for aROM calculation, of which the general principle is that the angle of rotation is given by the ratio of the arc length of motion to the radius of this arc. We tested a number of alternative formulae against available in vitro data to identify the most suitable geometric ratios and coefficients for accurate calculation. aROM values calculated with the developed formulae show significant correlation with in vitro data in SB, LB, and AR (Pearson r = 0.900) in the reference mammals (man, sheep, pig, cow). It was found that separate formulae for different zygapophysial facet types (radial (Rf), tangential (Tf), radial with a lock (RfL)) give significantly greater accuracy in aROM calculation than the formulae for the presacral spine as a whole and greater accuracy than the separate formulae for different spine regions (cervical, thoracic, lumbar). The advantage of the facet-specific formulae over the region-specific ones shows that the facet type is a more reliable indicator of the spine mobility than the presence or absence of ribs. The greatest gain in calculation accuracy with the facet-specific formulae is characteristic in AR aROM. The most important theoretical outcome is that the evolutionary differentiation of the zygapophysial facets in mammals, that is the emergence of Tf joints in the rib cage area of the spine, was more likely associated with the development of AR rather than with SB mobility and, hence, with cornering rather than with forward galloping. The AR aROM can be calculated with the formulae common for man, sheep, pig, and cow. However, the SB aROM of the human spine is best calculated with different coefficient values in the formulae than those for studied artiodactyls. The most suitable coefficient values indicate that the zygapophysial articular facets tend to slide past each other to a greater extent in the human thoracolumbar spine rather than in artiodactyls. Due to this, artiodactyls retain relatively greater facet overlap in extremely flexed and extremely extended spine positions, which may be more crucial for their quadrupedal gallop than for human bipedal locomotion. The SB, LB, and AR aROMs are quite separate in respect of the formulae structure in the cervical region (radial facet type). However, throughout the thoracolumbar spine (tangential and radial with lock facets), the formulae for LB and AR are basically similar differing in coefficient values only. This means that, in the thoracolumbar spine, the greater the LB aROM, the greater the AR aROM, and vice versa. The approach developed promises a wide osteological screening of extant and extinct mammals to study the sex, age, geographical variations, and disorders.     

Quantitative assessment and determinants of suture-holding capacity of human pancreas

Background

Hard pancreas is welcome by surgeons performing resective pancreatic surgery, because it is believed to offer better suture holding capacity (SHC), thus decreasing the risk for a postoperative leak. However, neither the actual SHC of pancreatic tissue in humans nor its determinants have been studied.

Methods

We directly measured SHC for polydioxanone 5–0 suture and tissue hardness at the pancreatic isthmus in 53 human pancreata using a dynamometer and a durometer. A histologic score based on fibrosis grade, fat content, pancreatic duct size, and signs of chronic pancreatitis was calculated for every sample. We tested the hypothesis that SHC of the pancreas was proportional to tissue hardness, and evaluated the role of different possible histomorphologic determinants of SHC.

Results

Suture-holding capacity correlated perfectly with tissue hardness (r = 0.98; P < 0.001; 95% confidence interval, 0.96–0.99). The histologic score showed a stronger correlation with both parameters than any single histologic parameter. The SHC of transductal sutures was significantly higher than that of pure transparenchymal sutures. The SHC and hardness were significantly lower in patients who developed a clinically relevant pancreatic fistula postoperatively.

Conclusions

A mixture of histomorphologic features of human pancreas determines its tissue hardness and SHC. Involvement of the main pancreatic duct in the suture line appears to increase the mechanical strength of the pancreatic anastomosis.     

Ion-selective electrode for quantitative determination of baclofen in pills

The possibility of determining baclofen in the anionic and cationic forms has been investigated. The main analytical characteristics of a cation-selective electrode reversible to baclofen were determined. A rapid potentiometric technique for baclofen determination in pills without long and laborious sample preparation is proposed.