Reversibility of Apixaban Anticoagulation with a Four-Factor Prothrombin Complex Concentrate in Healthy Volunteers.

It was hypothesized that the four-factor prothrombin complex concentrate (4F-PCC) Kcentra 25 unit/kg would reverse impairment of thrombin generation in healthy volunteers dosed with apixaban to steady state. In this randomized, two-period crossover, assessor-blinded trial, 12 healthy subjects received 5 mg apixaban every 12 h. Three h after the fifth dose, four-factor prothrombin complex concentrate (4F-PCC) 25 unit/kg or saline were infused. Serial blood samples were assessed for thrombin generation using PPP-reagent and PPP-reagent low, anti-Xa, PT, and PTT assays. Geometric mean ratio was calculated at 30 min postinfusion, and at 24, 48, and 72 h. Peak thrombin generation was 76% higher at 30 min postinfusion with 4F-PCC (p = 0.025). The difference declined to 24% at 24 h and resolved by 48 h. Other thrombin generation parameters were also partially normalized. There was no difference between 4F-PCC and saline in anti-Xa assessment at 30 min or later time points.

Waveform generator for electrical impedance tomography (EIT) using linear interpolation with multiplying D/A converters.

This paper describes the implementation of a multiplying digital-to-analogue (D/A) converter as a programmable waveform generator to be used in an electrical impedance tomography (EIT) system. Different digital techniques of generation waveforms are considered and the advantages and disadvantages of the chosen slope-plus-pedestal technique are presented. A wire-wrapped prototype system has been designed, and from measured frequency spectra the total harmonic distortion can be calculated to values between 1.1 and 2.9% depending on frequency.

A revised estimate of twin concordance in systemic lupus erythematosus.

OBJECTIVE: Based on a small clinical series and previously published case reports, concordance for systemic lupus erythematosus (SLE) among monozygous (MZ) twins has been reported to be as high as 69%. Using a larger and less biased sample, we provide another estimate of this percentage. METHODS: We established a registry of twins with SLE, based upon self-reports and information provided by the patients' physicians. We used DNA fingerprinting to validate the reported zygosity in a sample of these twins. RESULTS: Of 107 twin pairs meeting the American College of Rheumatology 1982 revised criteria for the diagnosis of SLE, 24% of 45 MZ pairs and 2% of 62 dizygous (DZ) pairs were concordant. The frequency distributions of diagnostic criteria and disease symptoms in the SLE patients were similar to those in other published reports of SLE patients. Zygosity was confirmed by DNA fingerprinting in a subsample of 15 self-described MZ twins and 7 self-described DZ twins. All individuals had correctly predicted their zygosity. CONCLUSION: MZ concordance for SLE is similar to that for other autoimmune diseases and is much lower than previously believed.

Recombination between feline leukemia virus subgroup B or C and endogenous env elements alters the in vitro biological activities of the viruses.

An important question in feline leukemia virus (FeLV) pathogenesis is whether, as in murine leukemia virus infection, homologous recombination between the infecting FeLV and the noninfectious endogenous FeLV-like proviruses serves as a significant base for the generation of proximal pathogens. To begin an analysis of this issue, several recombinant FeLVs were produced by using two different approaches: (i) the regions of the viral envelope (env) gene of a cloned FeLV (subgroup B virus [FeLV-B], Gardner-Arnstein strain) and those of two different endogenous proviral loci were exchanged to create specific FeLV chimeras, and (ii) vectors containing endogenous env and molecularly cloned infectious FeLV-C (Sarma strain) DNA sequences were coexpressed by transfection in nonfeline cells to facilitate recombination. The results of these combined approaches showed that up to three-fourths of the envelope glycoprotein (gp70), beginning from the N-terminal end, could be replaced by endogenous FeLV sequences to produce biologically active chimeric FeLVs. The in vitro replication efficiency or cell tropism of the recombinants appeared to be influenced by the amount of gp70 sequences replaced by the endogenous partner as well as by the locus of origin of the endogenous sequences. Additionally, a characteristic biological effect, aggregation of feline T-lymphoma cells (3201B cell line), was found to be specifically induced by replicating FeLV-C or FeLV-C-based recombinants. Multiple crossover sites in the gp70 protein selected under the conditions used for coexpression were identified. The results of induced coexpression were also supported by rapid generation of FeLV recombinants when FeLV-C was used to infect the feline 3201B cell line that constitutively expresses high levels of endogenous FeLV-specific mRNAs. Furthermore, a large, highly conserved open reading frame in the pol gene of an endogenous FeLV provirus was identified. This observation, particularly in reference to our earlier finding of extensive mutations in the gag gene, reveals a target area for potentially productive homologous recombination upstream of the functional endogenous env gene.

Analysis of somatic changes in human tumor DNA using synthetic oligonucleotide probes.

Like most hematologic malignancies, solid cancers may be associated with non-random chromosomal abnormalities. Heterogeneity in the cell population in solid cancers and the chromosomal variations occurring among primary, explant, and passaged cells of a given tumor, however, present a major difficulty in assessment of their cytogenetic changes. Alternative approaches to identifying specific somatic changes in subtypes of solid cancers, without cell culture manipulations, must be developed. This report describes preliminary evidence indicating that oligonucleotide probes, homologous to short tandem repeats, that can determine individual identity, may also be useful tools with which to examine somatic changes in DNA which has been isolated directly from a tumor mass. Two, of the four, bladder tumors (transitional cell carcinomas) analyzed, exhibited oligonucleotide-based DNA fingerprint patterns that differed from those of corresponding constitutive or uninvolved tissue DNA. The changes that were observed included gain or loss of hypervariable DNA fragments or shifts in band intensities.

Gastroesophageal reflux. Simple measures often suffice.

Regurgitation of the gastric contents into the esophagus is common and often unnoticed. When symptoms such as heartburn, a sour or bitter taste in the mouth, or even chest pain mimicking angina pectoris or myocardial ischemia prompt a patient to seek help, the factor or factors responsible for reflux must be sought. The possible underlying causes are numerous, as Dr Bachman points out in this discussion of the pathophysiology, diagnosis, and treatment of gastroesophageal reflux. The desired end point of management was well stated by Seneca over 2,000 years ago as "a good-humored stomach."

Marine noncholera Vibrio infections in Florida.

In the past decade, there has been a dramatic increase in the number of reported cases of clinical illness from noncholera (marine) vibrio infections, leading to a greater recognition of this potentially lethal disease. The wide spectrum of pathogenicity of this organism is reflected in the six cases in this report, varying from simple gastroenteritis to focal necrotizing cellulitis to fatal septicemia. We have reviewed the fundamental clinical differences between Vibrio vulnificus and other noncholera vibrio infections. Physicians treating patients with a history of exposure to coastal waters and/or seafood should be aware of the clinical features and the potential for significant morbidity and mortality of associated Vibrio vulnificus infections.