Best-practice algorithms for the use of a bilayered living cell therapy (Apligraf®) in the treatment of lower-extremity ulcers

Tissue-engineered skin substitutes such as Apligraf have emerged over the past 20 years as among the most carefully studied and efficacious of the advanced wound modalities. These products have been proven as effective enhancements to general wound care, promoting wound closure particularly in instances where conventional wound care fails. Marketed for hard-to-heal wounds since 1998, Apligraf has become part of standard wound care in many wound centers across the United States. Despite this situation, few general wound care guidelines incorporate advanced and active wound-healing technologies, such as tissue-engineered skin products. Because of this deficiency, appropriate patient selection and proper use of these product remain largely unaddressed within the general wound care community. Here, we describe the development of guidelines surrounding optimal use of the bilayered living cell therapy, Apligraf, in the treatment of the two types of lower extremity ulcers for which the product is FDA approved: venous leg ulcer and diabetic foot ulcer. The guidelines detailed in this article focus on the identification and selection of patients who are at risk for failure of standard wound care therapy and thus appropriate for Apligraf treatment. The intended audience for these guidelines is the general wound care practitioner, for whom the developed treatment algorithms and accompanying figure legends should provide practical, user-friendly direction simplifying both patient selection and appropriate use of Apligraf within the context of good wound-healing practice.     

The Effects of Feedback Sensory Modality, Feedback Information Content, and Sex on Short-Term Biofeedback Training of Three Responses

In three factorial experiments, auditory vs visual vs tactile feedback, analog feedback vs analog feedback which was anchored, and sex, were varied to assess the effects of these variables on performance in short-term biofeedback training of heart rate reduction, hand temperature increase, and forehead muscle tension reduction. A total of 108 subjects served in the study. Moderate but reliable changes were found during the course of the training session for all three physiological responses. The ability to reduce heart rate in a single training session did not appear to be a function of any of the variables manipulated in this study, but rather could be attributed to adaptation. In both muscle tension and temperature training, however, there were significant interactions between sex and sensory modality of the feedback stimulus and, in the case of muscle tension training, between information content of the feedback signal and sex. The overall pattern of results indicated that performance during biofeedback training is a complicated function of sex and the type of signal used to provide feedback, and that this function is not constant across physiological response systems.     

A failed fall prevention study in an acute care setting: Lessons from the swamp

Designing and implementing fall intervention studies in acute care settings presents researchers with a number of challenges. To date, there are no fall prevention interventions that have unequivocal empirical support in these settings. Based on the best available evidence a multistrategy fall prevention program was implemented using a pretest-post-test design over a 12-month period. The results indicated no reduction in the fall rate. Contrary to the expected result, the fall rate increased post the implementation of the multistrategy fall prevention program. To assist other researchers understand the contextual and methodological barriers to conducting fall prevention research in acute care settings, this paper discusses the difficulties experienced in this study.     

Body stature as a risk factor for diabetic sensory neuropathy

Risk factors for vibratory perception threshold abnormalities were studied in 200 diabetic patients between the ages of 21 and 70 years and 62 control subjects of similar age. Vibratory perception (measured with the Biothesiometer) was absent over one or both halluces in 18 percent of the patients. In a stepwise multiple logistic regression analysis, height was the variable most strongly associated with absent vibratory perception (coefficient ± SE, 0.501 ± 0.097/inch; p <0.0001). Duration of diabetes (p <0.001), age (p <0.05), and ethanol use (p <0.05) were also associated. The prevalence of absent vibratory perception in the lower, middle, and upper thirds of the height distribution was 0.05, 0.08, and 0.40, respectively. Among the control subjects, there was no association of vibratory perception with either height or ethanol use. These data strongly suggest that body stature is a major risk factor for diabetic sensory neuropathy.     

Naturally occurring infection of Pekin duck embryos by duck hepatitis B virus.

We tested the hypothesis that duck hepatitis B virus (DHBV) is a naturally occurring congenital infection of Pekin duck embryos. Of 219 embryos, 5-25 days after being laid, sera from 30 were found to be positive for endogenous DNA polymerase activity characteristic of hepatitis B-related viruses. The presence of the duck virus was confirmed by hybridization with cloned DHBV DNA. Viral DNA was also found in the livers of embryos incubated for 12 or 18 days. Electrophoretically different forms of DHBV DNA were identified in liver extracts that were not present in serum. These additional liver forms probably represent viral replication intermediates. These observations suggest that the vertical route is a major pathway of DHBV transmission and that viral replication may be initiated by the 12th day of embryonic life.     

Quinidine-digoxin interaction: Time course and pharmacokinetics

The time course of the rise in serum digoxin concentration was followed in 18 patients treated with digoxin as quinidine treatment was started with a loading dose. The mean serum digoxin levels rose significantly during the first 24 hours after administration of quinidine was begun, and reached a new steady state concentration after about 48 hours.

Digoxin kinetics were studied in two groups of normal volunteers: Group I (n = 7) received a small dose of quinidine, 800 mg/day, and group II (n = 8) received 1,600 mg/day. There was no significant mean change in the apparent volume of distribution of digoxin in either group. In group I (small dose), quinidine reduced the digoxin clearance values: total clearance by 30 percent, renal clearance by 32 percent and nonrenal clearance by 29 percent. In group II (large dose), quinidine reduced digoxin total clearance by 36 percent, renal clearance by 54 percent and nonrenal clearance by 22 percent. The reductions in digoxin volume of distribution and renal clearance during quinidine treatment were a function of the serum quinidine concentration. The change in nonrenal clearance of digoxin was independent of serum quinidine concentration.     

Analytical accuracy of determinations of aminoglycoside concentrations by enzyme multiplied immunoassay, fluorescence polarization immunoassay, and radioimmunoassay in the presence of heparin

The accuracy of gentamicin, netilmicin, and tobramycin concentration determinations by enzyme multiplied immunoassay technique (EMIT; Syva Corp., Palo Alto, Calif.), fluorescence polarization immunoassay (TDx; Abbott Diagnostics, Irving, Tex.), and radioimmunoassay were compared in the presence of 0 to 3,000 USP units of porcine heparin per ml. Gentamicin, netilmicin, and tobramycin concentrations determined by EMIT decreased by 10 and 50% in the presence of 75 and 1,000 USP units/ml, 2 and 5 USP units/ml, and 2 and 7.5 USP units/ml, respectively. Accuracy of the TDx and radioimmunoassay determinations, however, were not affected by the presence of heparin. Blood samples for the determination of gentamicin, netilmicin, and tobramycin by EMIT should not be collected in evacuated heparinized tubes.     

Genome of hepatitis B virus: restriction enzyme cleavage and structure of DNA extracted from Dane particles.

DNA extracted from Dane particles has been characterized by gel electrophoresis and restriction enzyme cleavage with endonuclease R-HaeIII (from Hemophilus aegyptius). Dane particle DNA is proposed to be a double-stranded circular DNA approximately 3600 nucleotides in length containing a single-stranded gap of 600-2100 nucleotides. The endogenous DNA polymerase (DNA nucleotidyl-transferase; deoxynucleosidetriphosphate:DNA deoxynucleotidyltransferase; EC 2.7.7.7) reaction appears to repair this single-stranded gap.