Clinical management of chronic hepatitis B infection: results from a registry at a German tertiary referral center.

PURPOSE: We studied a cohort of adult patients with chronic hepatitis B (CHB) infection, followed at a tertiary referral liver center in Germany over 12.5 years to analyze the clinical features and impact of management on disease progression and survival of CHB patients in general and of those with CHB and HCC in particular. METHODS: We retrospectively evaluated the medical records of 242 adult (age ≥ 18 years) patients. CHB was defined as positive hepatitis B surface antigen (HBsAg) and/or HBV-DNA levels >10 IU/mL for at least 6 months. Patient demographics, HBV markers, antiviral treatment, laboratory parameters, liver imaging and histology were recorded for each visit. HCC patients were divided into two groups and separately analyzed (group 1: n = 24, HCC at first visit and group 2: n = 11, HCC during surveillance). RESULTS: The mean age was 44 years in CHB patients without HCC (63% male) and about 59 years in patients with HCC (77% male). Antiviral therapy was given to 59% of patients without HCC compared to only 25% in group 1 and 18% in group 2 with comparable median HBV DNA levels of approximately 36,000 IU/mL. There was no statistically significant difference concerning the HCC stages (Milan, UCSF, BCLC) at first diagnosis. Five-year survival was 19% in group 1 vs. 64% in group 2 (p = 0.019), with LTx performed in 12 vs. 45%, respectively. CONCLUSION: Surveillance of CHB patients did not result in early stage detection of HCC but in a higher likelihood to receive potentially curative treatments.

Classical-NOVA CONTRIBUTION to the Milky Way's ²6Al abundance: exit channel of the key ²5Al(p,γ) ²6Si resonance.

Classical novae are expected to contribute to the 1809-keV Galactic γ-ray emission by producing its precursor 26Al, but the yield depends on the thermonuclear rate of the unmeasured 25Al(p,γ)26Si reaction. Using the ß decay of 26P to populate the key J(π)=3(+) resonance in this reaction, we report the first evidence for the observation of its exit channel via a 1741.6±0.6(stat)±0.3(syst) keV primary γ ray, where the uncertainties are statistical and systematic, respectively. By combining the measured γ-ray energy and intensity with other experimental data on 26Si, we find the center-of-mass energy and strength of the resonance to be E(r)=414.9±0.6(stat)±0.3(syst)±0.6(lit.) keV and ωγ=23±6(stat)(-10)(+11)(lit.) meV, respectively, where the last uncertainties are from adopted literature data. We use hydrodynamic nova simulations to model 26Al production showing that these measurements effectively eliminate the dominant experimental nuclear-physics uncertainty and we estimate that novae may contribute up to 30% of the Galactic 26Al.

Central Slip Repair using Trans-articular K-wires: A Comparative Study.

Central slip disruption may lead to PIP joint dysfunction causing significant morbidity. Existing evidence for any specific surgical management of these injuries is limited but does favor early mobilization of the PIP joint. Aim: To assess the functional outcome in a cohort of patients undergoing central slip repair with internal K-wire proximal interphalangeal joint splinting and complete immobilization against those with external splinting only. Methods: A single center retrospective analysis of all patients that underwent operative central slip repair in our institution over a 5-year period. Data were collected via the HIPE database and clinical notes. Data relating to demographics as well as range of motion, total active motion {(TAM) (TAM%)} score, and hand therapy rehabilitation type were analyzed. Results: The study population was n = 44 patients. N = 33 patients were treated without a K-wire and n = 11 treated with a K-wire. There was a male predominance, 81.8% (n = 36). Mean age was 40.4 years. There was no significant difference in the mean TAM achieved at final measurement between the "no K-wire" and the "K-wire" treatment groups [no K-wire 202.1° (standard deviations (SD) 40.0) vs. K-wire 187.4° (SD 28.2), p = 0.208]. The "no K-wire group" achieved a mean TAM % of 78.0 (SD 11.4) and the "K-wire group" achieved a mean TAM % of 72.1 (SD 10.8); no statistically significant difference in mean scores was observed between groups. Conclusion: Our study has shown comparable functional outcomes between those having complete joint immobilization with internal K-wire splinting and those that are externally splinted only following central slip repair.

Bowel preparation prior to percutaneous ilio-sacral screw insertion: is it necessary?

PURPOSE: The aim of this study was to compare the outcomes of ilio-sacral (IS) screw fixation with and without the use of bowel preparation, in terms of obtaining adequate visualisation, malpositioning of screw requiring revision surgery and neurovascular injury. METHODS: A retrospective case control study was performed. We reviewed 74 consecutive cases of IS screw fixation performed at our institution within the last 5 years. We included all patients who had undergone percutaneous IS screw fixation. Two groups, one consisting of patients who underwent bowel preparation prior to surgery (Group 1) and one consisting of patients who had no bowel preparation (Group 2), were compared in terms of the above outcomes. There were 37 patients in each group. The mean age in Group 1 was 41 years (17-63) and in Group 2 was 47 years (12-89). RESULTS: In Group 1 there were two procedures abandoned due to poor visualisation. In Group 2 there were no cases abandoned for poor visualisation. There were two nerve injuries in Group 1 and no nerve injuries in Group 2. Revision surgery was performed in four patients in Group 1-for malposition, persistent buttock pain, sciatic nerve palsy and inadequate fixation while one revision performed in Group 2 for persistent buttock pain. CONCLUSION: Based on these results, we conclude that bowel preparation is not necessary to obtain adequate visualisation for safe and accurate percutaneous IS screw insertion. In fact, in Group 1 two procedures were abandoned and there was higher incidence of complications. Therefore, it would appear that this treatment arm should be abandoned all together. Further studies to prove it conclusively and explain the reasons are required.

Fragile sites are targets of diverse mutagens and carcinogens.

Using a high-resolution chromosome banding technique with cultured human lymphocytes and caffeine as a mutagen enhancer, 16 different mutagens and carcinogens were found to induce 110 recurrent fragile sites. All agents produced chromosome breaks and the majority of the 110 recurrent break sites involved were elicited by at least half of all agents, even though they act through different molecular mechanisms. Two of the agents used are known to induce hypersensitive chromatin sites in regulatory regions of active genes. Of the 110 mutagen-sensitive fragile sites, 50 coincide with the location of 50 of 75 specific cancer chromosome breakpoints (67%) and 21 with the location of 26 of 36 oncogenes (72%). The expression of so many similar fragile sites following exposure of cultured cells to diverse mutagens, and the high correlation of these sites with cancer chromosome breakpoints and oncogenes, suggests that they can be general targets of mutagenic action.

Gasoline and flammable and nonflammable clothing studies.

Studies were conducted on mannequins using gasoline and flammable and nonflammable children's clothing. The results indicate that the flame-resistant standards currently required by law for children's sleepweare lead to much less severe burns.

Salmonella berta meningitis in a term neonate.

We report the case of a 37-week male infant born via spontaneous vaginal delivery who developed Salmonella berta sepsis and meningitis. The infant was born to a mother with active diarrhea and stool cultures growing S. berta. On day 3, the infant developed poor feeding, lethargy, apnea and bradycardia prompting a sepsis evaluation. Blood, stool and cerebrospinal fluid cultures were positive for S. berta. An electroencephalogram performed for posturing revealed neonatal status epilepticus. Extensive bilateral periventricular venous hemorrhagic infarctions with multiple herniations were seen on brain magnetic resonance imaging. The infant's condition continued to deteriorate despite maximal support and care was redirected towards comfort measures.

The effects of magnesium sulfate infusion on blood pressure and vascular responsiveness during pregnancy.

Magnesium sulfate is primarily used for its anticonvulsive effects in treating hypertensive disorders of pregnancy. However, we have frequently observed significant falls in blood pressure in patients suffering from severe pregnancy-induced hypertension in whom little or no additional hypotensive medication was necessary for maintenance of diastolic blood pressure at 90 to 100 mm Hg while using recommended doses of this drug. We compared resting mean arterial pressure and vascular response to infusions of 50 ng/kg/min of angiotensin II and 2500 ng/kg/min of Levophed (norepinephrine) before and during infusion of a loading dose of 200 mg of magnesium sulfate intravenously in 15 minutes, followed by continuous infusions of 50 and 100 mg/hr intravenously in chronically prepared virgin (n = 14) and primigravid (n = 12) rabbits at 24 to 28 days' gestation (term = 30 +/- 1 day). Resting mean arterial pressure and vascular response to angiotensin II and norepinephrine were significantly decreased in the primigravid and virgin animals. Magnesium sulfate may attenuate blood pressure by decreasing the vascular response to pressor substances.

Bilateral partial ruptures of the flexor carpi radialis tendon secondary to trapezial arthritis.

This is a report of bilateral partial ruptures of the flexor carpi radialis tendons associated with trapezial osteoarthritis. Splinting for 4 weeks was curative. One of the tendons was exposed 4 months after rupture in conjunction with carpal tunnel release and the abnormal healed tendon was revealed.

Surface degradation features and microstructural properties of ultra-high molecular weight polyethylene (UHMWPe).

Surface degradation of UHMWPe is recognized as a leading clinical concern, limiting the long-term performance in total knee replacements. Eight retrieved tibial plateaux and six wear screening test samples were evaluated for surface degradation features and microstructural features. The surface degradation features were assessed using stereomicroscopy and scanning electron microscopy. Microstructural features were evaluated using optical microscopy of thin cross-sections and a permanganate etching technique. The pitting mechanism of wear was observed on all eight retrieved TKR and covered an average of 12.6% of the surface area. The size of the pits were similar to the size of grains observed in the microstructural evaluation - approximately 100 to 200 microm. The presented observations of pitting in retrieved knee implants have shown that the post-processing microstructure may influence this mechanism of surface degradation and hence the wear products.

Effect of melatonin on hemolymph glucose and lactate levels in the fiddler crab Uca pugilator.

Melatonin was injected into intact and eyestalk-ablated fiddler crabs (Uca pugilator), and its effects on hemolymph glucose and lactate levels were studied. In intact crabs, glucose and lactate levels cycled simultaneously, with peaks occurring during early and late photophase. Melatonin caused a shift in the glucose and lactate cycles, with only one peak occurring closer to mid-photophase. In eyestalk-ablated animals, the glucose rhythmicity was lost; lactate cycled, but levels were significantly lower than in intact animals. Melatonin caused a delayed hyperglycemia in eyestalk-ablated animals, with concurrent but much lower increases in lactate. Overall, melatonin demonstrated delayed hyperglycemic effects that do not appear to be mediated solely via eyestalk factors such as crustacean hyperglycemic hormone (CHH), though involvement of the eyestalks cannot be ruled out. An influence on extra-eyestalk CHH secretion is a potential mechanism of melatonin activity.

The region surrounding the PKD1 gene: a 700-kb P1 contig from a YAC-deficient interval.

As part of an effort to identify the gene responsible for the predominant form of polycystic kidney disease (PKD1), we used a gridded human P1 library for contig assembly. The interval of interest, a 700-kb segment on chromosome 16p13.3, can be physically delineated by the genetic markers D16S125 and D16S84 and chromosomally characterized as a GC-rich isochore enriched for CpG islands, genes, and Alu-like repeats. Our attempts to recover CEPH YACs that encode this region of chromosome 16 were unsuccessful. However, we screened an arrayed P1 library using 15 distinct probes from the D16S125-D16S84 interval and identified 56 independent P1 clones. Only one probe from the interval was unsuccessful in identifying a P1 clone. Forty-four P1 clones were determined to be unique based on restriction enzyme analysis, and 42 of these were found to originate from chromosome 16p13.3, based on FISH to metaphase chromosomes. The 700-kb interval could be defined by a single sequence-ready contig comprised of 12 P1 clones and 1 cosmid clone. Our studies support the use of multiple libraries to generate the requisite physical reagents for positional cloning and encourage the use of Escherichia coli-based large-insert cloning systems to recover clones from YAC-deficient chromosomal intervals.

FGF-23 inhibits renal tubular phosphate transport and is a PHEX substrate.

Oncogenic osteomalacia (OOM), X-linked hypophosphatemia (XLH), and autosomal dominant hypophosphatemic rickets (ADHR) are phenotypically similar disorders characterized by hypophosphatemia, decreased renal phosphate reabsorption, normal or low serum calcitriol concentrations, normal serum concentrations of calcium and parathyroid hormone, and defective skeletal mineralization. XLH results from mutations in the PHEX gene, encoding a membrane-bound endopeptidase, whereas ADHR is associated with mutations of the gene encoding FGF-23. Recent evidence that FGF-23 is expressed in mesenchymal tumors associated with OOM suggests that FGF-23 is responsible for the phosphaturic activity previously termed "phosphatonin." Here we show that both wild-type FGF-23 and the ADHR mutant, FGF-23(R179Q), inhibit phosphate uptake in renal epithelial cells. We further show that the endopeptidase, PHEX, degrades native FGF-23 but not the mutant form. Our results suggest that FGF-23 is involved in the pathogenesis of these three hypophosphatemic disorders and directly link PHEX and FGF-23 within the same biochemical pathway.