Adherence to topical dermatological therapy: lessons from oral drug treatment.

Patients are remarkably nonadherent to medical treatment regimens across all diseases and classes of therapy, and it has been estimated that nonadherence to drug treatment is responsible for as many as 10% of all hospital admissions. Nonadherence to treatment also has significant negative effects on treatment outcomes across a wide range of diseases. Patient-related factors such as age, ethnicity, literacy (including health literacy), health beliefs, and socioeconomic conditions have been shown to influence adherence to oral therapy. Medication-related factors, such as regimen complexity and duration of treatment, also impact on adherence. Variables that significantly influence adherence to oral drugs have similar effects on adherence to topical therapy. Both educational and psychological interventions along with simplification of dosing regimens can significantly improve adherence to oral therapy and limited evidence indicates that these approaches are also effective in patients receiving topical therapy. There is very little information about the effects of dosing regimens on adherence to topical medical therapy. The advent of new drug formulations that permit once-daily or single-dose drug application will, however, permit evaluation of different topical treatment regimens on adherence and treatment outcomes in patients with dermatological disease.

Purely internal thoracic artery grafts: outcomes.

BACKGROUND: Most of our patients with coronary artery disease have undergone bypass exclusively with purely internal thoracic artery grafts (PITA). Our goal has been to lengthen the time a patient benefits from coronary bypass operations. The present report describes an 8.5-year study of outcomes including mortality and the need for reintervention in patients who have undergone bypass with PITA. METHODS: We studied 897 patients who underwent PITA with a total of 3,784 internal thoracic artery (ITA) grafts (4.2 grafts per patient). Connecting ITA to ITA along with sequential anastomosis made the procedure possible. RESULTS: Early mortality for the group was 2.3%. Freedom from death was 86% and freedom from reintervention was 94% at 5 years after the operation. CONCLUSIONS: The acceptable early and late mortality and the 94% freedom from reintervention as long as 8.5 years after operation in this group of patients inspire us to continue choosing PITA for patients with three-vessel coronary artery disease.

Relationship between terrain use and performance of beef cows grazing foothill rangeland.

A study was conducted on foothills rangeland to determine whether grazing patterns differed among cow breeds and to determine whether there was a relationship between individual grazing patterns and performance of beef cows. Hereford (HH), Tarentaise (TT), 3/4 Hereford x 1/4 Tarentaise (3H1T), 1/2 Hereford x 1/2 Tarentaise (HT), and 1/4 Hereford x 3/4 Tarentaise (1H3T) cows were observed during the summers of 1997 (n = 183) and 1998 (n = 159). Locations of individual cows were recorded two to three times per week during 1.5- to 2.5-h periods in the morning by observers on horseback. Statistical models included cow breed, age, and nursing status. Data from each year were analyzed separately. During 1997 and 1998, nonlactating cows were located at greater (P < 0.05) vertical distances from water than lactating cows. In 1998, nonlactating cows used steeper (P < 0.05) slopes than lactating cows. However, nonlactating cows did not travel as far horizontally from water (P < 0.05) as lactating cows in 1997. Younger cows (3 yr) traveled further (P < 0.05) from water both vertically and horizontally than older cows (5+ yr) in 1997, but not during 1998. Tarentaise and 1H3T cows were observed at greater (P < 0.05) vertical distances from water than HH cows during both years of the study. During 1998, TT and 1H3T cows used steeper (P < 0.05) slopes than HH cows. Using residual correlations, there were no consistent relationships between topographic aspects of individual grazing locations and cow weight, height, and body condition score. In 1997, cows with earlier calving dates and correspondingly heavier calf weaning weights used areas that had greater vertical distances to water; however, in 1998 there were no relationships (P > 0.05) of calving date and weaning weight with cow location. During both years, pregnant and nonpregnant cows used terrain similarly (P > 0.05), which suggests that cow reproductive performance was not related to terrain use. Grazing patterns in foothills rangeland varied among cow breeds. Performance of cows that used more rugged topography was similar to cows using gentler terrain.

Immunotherapy of HIV-infected patients with intermittent interleukin-2: effects of cycle frequency and cycle duration on degree of CD4(+) T-lymphocyte expansion.

The ability of IL-2 to induce expansion of the CD4(+) T lymphocyte pool has made it the most studied cytokine in the treatment of HIV infection. The majority of trials have used an empirical regimen of 5-day IL-2 cycles given every 8 weeks--a regimen based upon early pharmacodynamic studies and patient preference. To better define optimal duration and frequency of cycles, a randomized trial was conducted in which patients who received this "standard" regimen were compared to patients who received cycles of variable duration (based on individual patterns of cell cycle progression) and to patients who received cycles of variable frequency (based on individual CD4(+) T lymphocyte responses to previous cycles). Twenty-two patients with HIV-1 infection and CD4(+) T lymphocyte counts > 200 cells/mm(3) were randomized to one of three treatment groups for 32 weeks of study. Eight participants received four 5-day IL-2 cycles (controls) every 8 weeks; 7 participants received four cycles of longer duration (mean 7.7-days); and 7 participants received an increased frequency of 5-day cycles (every 4.1 weeks on average). All three groups experienced significant increases in mean CD4(+) T lymphocytes. However, there were no statistically significant differences in CD4(+) T lymphocyte increases between the group that received longer cycles (median increase 239 cells/mm(3), P = 0.78) or between the group that received more frequent cycles (median increase 511 cells/mm(3), P = 0.54) and the control group (median 284 cells/mm(3)). HIV-1 viral loads decreased during the study period in all three groups. Our inability to demonstrate a significant advantage of increased frequency or duration of IL-2 administration provides corroborating experimental evidence for the use of an IL-2 regimen consisting of 5-day cycles administered no more frequently than every 8 weeks in future clinical trials aimed at expanding the CD4(+) T lymphocyte pool.

Genetic evaluation of carcass traits in Simmental-sired cattle at different slaughter end points.

Our objectives were to estimate genetic parameters for carcass traits and evaluate the influence of slaughter end point on estimated breeding values (BV). Data provided by the American Simmental Association were divided into three sets: 1) 9,604 records of hot carcass weight (CW) and percentage retail cuts (PRC), 2) 6,429 records of CW, PRC, and marbling score (MS), and 3) 1,780 records of CW, PRC, MS, fat thickness (FT), and longissimus muscle area (LMA). Weaning weights (WW) from animals with carcass data and from their weaning contemporaries were used. Data were analyzed with a multiple-trait animal model and REML procedures to estimate genetic parameters and BV on an age-, CW-, MS-, or FT-constant basis. The model for carcass traits included fixed contemporary group and covariates for breed, heterozygosity, and slaughter end point and random additive direct genetic and residual effects. Weaning weight was preadjusted for founder effects, direct and maternal heterosis, age of dam, and age of calf. The model for WW included fixed contemporary group and random additive direct genetic, maternal genetic, maternal permanent environment, and residual effects. Heritabilities from data set 1 were 0.34 for CW and 0.25 for PRC on an age-constant basis and 0.25 for PRC on a CW end point. Heritabilities for data set 2 were 0.35, 0.24, and 0.36 for CW, PRC, and MS, respectively, on an age-constant basis. Data set 2 heritabilities were 0.25 for PRC and 0.34 for MS on a CW-constant basis and 0.33 for CW and 0.25 for PRC at a constant MS end point. Heritabilities on an age-constant basis for data set 3 were as follows: CW, 0.32; PRC, 0.09; MS, 0.12; FT, 0.10; and LMA, 0.26. Heritability estimates for data set 3 on a CW-, MS-, and FT-constant basis were similar to those on an age-constant basis. Heritabilities were 0.12 for PRC, 0.12 for MS, 0.14 for FT, and 0.22 for LMA on a CW-constant basis; 0.30 for CW, 0.09 for PRC, 0.10 for FT, and 0.28 for LMA at a constant MS end point; and 0.33, 0.17, 0.13, and 0.29 for CW, PRC, MS, LMA on a FT-constant basis. Genetic correlations among traits varied across groups and end points but suggested that it should be possible to select for improved lean yield without sacrificing quality grade. Correlations were calculated among BV computed at different end points. Adjustment to various end points resulted in some changes in BV and reranking of sires, especially for PRC; however, the number of records available had a larger influence than slaughter end point.

The effect of ritonavir on the pharmacokinetics of meperidine and normeperidine.

STUDY OBJECTIVE: To determine the effects of ritonavir on the pharmacokinetics of meperidine and normeperidine. DESIGN: Open-label, crossover, pharmacokinetic study. SETTING: United States government research hospital. SUBJECTS: Eight healthy volunteers who tested negative for the human immunodeficiency virus. INTERVENTION: Subjects received oral meperidine 50 mg and had serial blood samples collected for 48 hours. They then received ritonavir 500 mg twice/day for 10 days, followed by administration of a second 50-mg meperidine dose and collection of serial samples. MEASUREMENTS AND MAIN RESULTS: Plasma samples were assayed for meperidine, normeperidine, and ritonavir. Meperidine's area under the curve (AUC) decreased in all subjects by a mean of 67+/-4% in the presence of ritonavir (p<0.005). Mean +/- SD maximum concentration was decreased from 126+/-47 to 51+/-21 ng/ml. Normeperidine's mean AUC was increased 47%, suggesting induction of hepatic metabolism. CONCLUSION: Meperidine's AUC is significantly reduced, not increased, by concomitant ritonavir. Based on these findings, the risk of narcotic-related adverse effects from this combination appears to be minimal. However, increased concentrations of normeperidine suggest a potential for toxicity with increased dosages or long-term therapy.

Management of collagen vascular diseases in childhood.

Collagen vascular diseases seen in children include systemic, discoid and neonatal lupus, dermatomyositis, scleroderma, juvenile rheumatoid arthritis, and, in rare cases, Sjogren's syndrome. Although these diseases are uncommon in children, when seen, they are associated with significant morbidity. This review describes the clinical features of each condition and provides an overview of treatment options now available. These include numerous systemic treatments which can be used as steroid-sparing agents.

Transition from cardiopulmonary bypass to the HeartMate left ventricular assist device.

BACKGROUND: Safe transition from cardiopulmonary bypass to the HeartMate left ventricular assist device without periods of low output, air emboli, or injury to the right ventricle is vital to its successful implantation. A right atrial-to-left ventricular shunt has been developed to purge quickly and completely all air from the system and prevent its reentry, as well as to assist the right ventricle during the transition from cardiopulmonary bypass to the HeartMate. METHODS: From January 1994 through July 1996, we used an extracorporeal membrane oxygenation right atrial-to-left ventricular shunt during 17 HeartMate implantations in 16 patients. The shunt consists of the existing right atrial two-stage cannula, the bypass circuit, and a separate aortic line that fills the left ventricle using a 21F cannula in the lateral ventricular wall. Air is monitored in the heart and aorta using transesophageal echocardiography. RESULTS: Ten of the 16 patients are living and 8 have undergone transplantation. Two patients are still using the device and are awaiting transplantation. None of the patients have experienced postoperative neurologic events suggestive of air emboli. CONCLUSIONS: The extracorporeal membrane oxygenation right atrial-to-left ventricular shunt is simple and inexpensive to construct. It provides for a smoother and safer transition from cardiopulmonary bypass to the HeartMate left ventricular assist device.

Heterosis and breed additive effects for Hereford, Tarentaise, and the reciprocal crosses for calf traits.

Records from 595 straightbred Hereford (HH), straightbred Tarentaise (TT), and reciprocal-cross (HT) females, randomly mated to HH, TT, or HT bulls, were analyzed for estimates of heterosis and breed additive effects for calf traits that included birth weight (BWT), calving difficulty (DIFF), prebreeding (PRE) and postbreeding (PST) weight, weaning weight (WWT), weaning condition score (WCS), weaning hip height (WHH), and preweaning average daily gain (ADG). The statistical model included year, age of dam, sex, regression on age at time of measurement, and regressions for the genetic effects of breed individual, breed maternal, breed grandmaternal, individual heterosis, and maternal heterosis. Breed effects were coded to reflect TT- HH differences. Age at the time of measurement, year, age of dam, and sex were significant for most traits. Individual breed effects were important (P < .05) for BWT, PRE, PST, WCS, and WHH but not for WWT, resulting in lower weights, less condition, and taller animals for TT. Maternal breed effects did not influence BWT, but they were important ( P < .05) for PRE, PST, WWT, WCS, WHH, and ADG. Grandmaternal effects were only important for BWT and ADG. Individual and maternal heterosis were important (P < .05) for most traits measured, resulting in increased calf size, weight, and body condition.

A rat model for the evaluation of small-caliber vascular grafts.

This article describes the development of a new experimental model using rats for the evaluation of small-caliber vascular grafts. By modifying heterotopic heart transplantation, two 1.5- to 2.0-cm long vascular prostheses were interposed between a syngeneic donor heart and the recipient abdominal vessels in the form of vascular bridges. Once blood flow through the vascular grafts was reestablished, the donor heart resumed normal beating. The status of the vascular grafts could be easily monitored by palpation. Occlusion of the grafts stopped donor heart beating without affecting survival of the animals. Once the surgical method was mastered, the postoperative mortality was approximately 10%, and the total procedure took less than 2 hours. Although microvascular surgical technique and equipment are required, this model has several advantages, including easy detection of thrombotic occlusion of the grafts, the use of small animals of defined genetic background, the absence of effect of graft occlusion on the recipient's life, and possible repeated operation on the same animal.

Preoperative depletion of C3 improves the survival of guinea pig-to-rat cardiac xenograft recipients.

Rat strains with congenitally reduced total hemolytic complement activity do not reject cardiac xenografts hyperacutely. Prolongation of graft survival in the guinea pig-to-C6-deficient PVG rat donor/recipient combination has been observed. However, experience with this model has been complicated by a high postoperative mortality from respiratory distress. The authors hypothesized that placement of the xenograft resulted in local activation of complement, which contributed to remote pulmonary injury leading to respiratory dysfunction. To test this hypothesis, an attempt was made to reduce early complement component activation with the use of an antibody to rat C3 in C6-deficient PVG recipients. Six of eight untreated C6-deficient PVG recipients died in the immediate postoperative period with vigorously beating heart grafts, whereas only 2 of 14 C6-deficient recipients pretreated with anti-rat C3 antibody died within 24 h postoperatively. Although pretreatment with anti-C3 antibody improved survival of recipients, the duration of cardiac xenograft survival was similar whether the recipients were pretreated or not. The use of anti-C3 antibody in C6-deficient rats is a valid approach to studying xenotransplantation in the absence of hyperacute rejection and has an additional advantage in that it does not require the use of expensive reagents such as cobra venom factor.

Genetic components for milk production of tarentaise, hereford, and tarentaise x hereford cows.

The objective of this study was to estimate genetic components for milk production of Hereford (HH), Tarentaise (TT), and Hereford x Tarentaise or Tarentaise x Hereford (HT) cows under range conditions at the Northern Agricultural Research Center, Havre, MT. Milk production of 494 cow-calf pairs was estimated by the weigh-suckle-weigh procedure from 1989 to 1994. Milk production and cow and calf weights were measured at 40 d (early) and 120 d (late) of lactation. The mating scheme was a 3 x 3 design in which HH, HT, and TT cows were mated with HH, HT, and TT sires, producing calves that were varying percentages of Hereford and Tarentaise. Data were analyzed by least squares procedures according to a model that included year, age of cow, sex of calf, linear regression on calf age, and linear regressions on coefficients that coded for various genetic components. These genetic components were breed individual, breed maternal, breed grand maternal, individual heterosis (calf heterosis), and maternal heterosis (cow heterosis). Coefficients for genetic components were such that breed effects estimated TT-HH and regressions on heterosis values estimated the full effect of heterosis. The breed individual genetic component was significant only for calf early and late weights; Tarentaise calves were lighter. Breed maternal was significant for most traits, and these effects were positive for milk production (2.16 and 3.77 kg/d for early and late, respectively) and calf weights but negative for cow weights. Individual heterosis was not significant for early milk production but was significant for late milk production (1.05 kg/d) and calf weights (2.3 and 8.1 kg for early and late, respectively). Maternal heterosis was significant for most traits and increased early milk production (1.25 kg/d), calf weights (4.5 and 5.8 kg for early and late, respectively), and cow weights (18.1 and 6.0 kg for early and late, respectively).

Factors influencing genetic evaluations of linebred Hereford cattle in diverse environments.

Data from four closely related Line 1 Hereford herds were used to estimate variance components and predict EPD for birth weight (BWT), weaning weight (WWT), and postweaning gain (PWG). Herds were located in diverse environments and differed in level of phenotypic performance. Within-herd BWT analyses considered effects of inbreeding of calf and dam, sex, age of dam (AOD), and contemporary group as fixed and direct and maternal additive genetic effects and permanent environmental effects due to dam as random. The model for WWT included these effects and age of calf. The model for PWG included inbreeding of calf, contemporary group, and direct additive genetic effects. Across-herd analyses were conducted with additional models. The first considered herd-specific inbreeding, sex, and AOD effects. A second model pooled these effects across herds, and a third included pooled sex and AOD effects but ignored inbreeding. Across-herd EPD, including and ignoring inbreeding, were predicted for WWT preadjusted with standard adjustments for Hereford cattle. Within-herd analyses indicated potential for heterogenous genetic and environmental variances across herds. Across-herd variance component estimates were consistent, regardless of the model. Estimates of genetic trends indicated potential for bias in genetic evaluations resulting from choice of model. Differences in magnitude of fixed effects between herds were observed. Genetic evaluations were different when pooled or herd-specific fixed effects were used. Allowance for individual herd differences in fixed effects in across-herd evaluations is suggested.

Olmsted syndrome. Case report and identification of a keratin abnormality.

BACKGROUND: Olmsted syndrome is a rare disorder characterized by a mutilating palmoplantar keratoderma and periorificial keratotic plaques. It begins in early childhood and is complicated by the development of painful flexion contractures, constrictions, and autoamputations of the digits. Only 11 cases of Olmsted syndrome have been reported to date. However, no biochemical abnormalities in the skin were reported in any of these cases. OBSERVATIONS: We report the 12th case of Olmsted syndrome. In addition, we describe a keratin abnormality found in a skin specimen obtained from our patient. The specimen showed a suprabasilar staining pattern with AE1, an antibody that shows only basilar staining in normal skin. CONCLUSION: We report the 12th case of Olmsted syndrome, review the literature, and describe a keratin abnormality that was found in our patient's skin specimen.

Complete revascularization with internal thoracic artery grafts.

Saphenous vein graft atherosclerosis continues to be the major cause of late failures of coronary artery bypass operations (CABG). The internal thoracic artery (ITA) is an ideal bypass graft because it remains free of atherosclerosis at late follow-up in most patients. Myocardial revascularization with only ITA grafts has developed in an incremental manner from single grafts of the left ITA to the left anterior descending coronary artery (LAD), to use of bilateral, free and sequential ITAs, and now recently to the use of preconstructed grafts that attach the free right ITA to the left ITA. The microanatomy and vascular reactivity of the ITA have been recently defined, and they explain why the ITA remains free of obstruction. Our techniques and results of ITA grafting developed over the past 25 years are presented.

Tarentaise and Hereford breed effects on cow and calf traits and estimates of individual heterosis.

Preweaning and weaning records on 457 calves and weights and milk production of their dams were used to evaluate breed of dam effects, breed of sire effects, and individual heterosis effects. Hereford and Tarentaise dams were mated to Hereford and Tarentaise sires and calves were born from 1987 to 1991. Calf traits were birth weight, proportion calving difficulty, weaning weight, weaning height, weaning weight:height ratio, and condition score at weaning. Cow traits were milk production four weights during the year, weight changes, height at weaning, condition score, ratio of calf weight:cow weight, proportion calved and weaned, and calf weaning weight per cow exposed to breeding. Breed of sire was nonsignificant for all traits except calf hip height, but breed of dam was significant for calf weaning weight and condition score, late milk production, change in milk production, and the cow traits of all weights, condition score, weight:height ratio, and ratio of calf weight:cow weight. Least squares means for Hereford and Tarentaise dams, respectively, were 216 and 236 kg for calf weaning weight, 6.2 and 9.3 kg for late milk production, 559 and 507 kg for cow weight at weaning, 6.0 and 4.9 for cow condition score, and .39 and .47 for ratio of calf weight at weaning:cow weight at weaning. Heterosis was significant for birth weight (1.05 kg, 3%, P = .01), weaning weight (11.0 kg, 5%, P = .01), and condition score (.13, 2%, P = .06). Thus, Hereford dams weighted more and had higher levels of condition, whereas Tarentaise dams produced more milk late in lactation and weaned heavier calves.

Reoperation in patients with closed SVG and patient LITA-LAD graft: T-graft approach.

Selection of the bypass graft that the patient has demonstrated will remain patent and free from critical atherosclerosis is a most important part of coronary artery bypass reoperations. Sixteen patients in whom a patent left internal thoracic artery-left anterior descending coronary artery bypass graft and obstructed or closed saphenous vein grafts to other coronary arteries were visualized underwent reoperation. To reach the inadequately perfused circumflex and right coronary arteries, the right internal thoracic artery was anastomosed to the left internal thoracic artery as a T graft and then was attached to the circumflex and right coronary artery branches. All patients survived the procedure and are free from angina. There were no perioperative myocardial infarctions, and there was no suggestion of hypoperfusion by the grafts. We believe this technique may reduce the incidence of graft failure in patients undergoing reoperative coronary artery bypass grafting.

T-graft: a new method of coronary arterial revascularization.

We present early results in 486 patients undergoing total coronary artery revascularization using a T-graft constructed from the attached left internal thoracic artery (LITA) and the free right internal thoracic artery (RITA). The anterior and anterolateral areas of the heart are by-passed with the LITA and the inferolateral, inferior and posterior areas are by-passed with the RITA. These patients received an average of 4.34 distal anastomoses with as many as four from each of the limbs of the T-graft. Ages ranged from 29 to 89 years and ejection fractions from 15 to 79%. Sixty-six patients were undergoing first reoperations and 6 received T-grafts at their second reoperation. The mortality at 30 days was 2.3%. Two of 92 women and 9 of 394 men expired. The perioperative infarction rate was 1.2%. Postoperative angiography in 34 patients showed 98.3% of LITA and 86.5% of RITA anastomoses to be patent. There was a slightly higher patency observed in women. The T-graft technique can be applied to nearly all patients with 3 vessel coronary artery disease with low operative mortality. Precise technique with high power magnification is crucial. This procedure has the potential of avoiding further invasive procedures due to graft deterioration in many patients with 3 vessel coronary artery disease.

Life cycle evaluation of five biological types of beef cattle in a cow-calf range production system: I. Model development.

Data collected during a 10-yr study at the Northern Agricultural Research Center (NARC), Havre, MT were used in construction of a simulation model to evaluate production systems using different breed groups. Five dam breed groups, straightbred Hereford (HH), 50% Angus-50% Hereford (AH), 25% Simmental-75% Hereford (1S3H), 50% Simmental-50% Hereford (1S1H), and 75% Simmental-25% Hereford (3S1H), were studied. The simulated system was a northern range cow-calf production system with spring calving and fall weaning. Replacement heifers were purchased and all calves were marketed at weaning. All nonpregnant females were sold in the fall. Statistical analyses of the data yielded input values (least squares means for breed group x age x sex subclasses) for cow and calf weights, pregnancy rate, dystocia, and calf survival. Pregnancy, dystocia, calf survival, calf weights, and cow weights were simulated stochastically. Energy requirements for maintenance, growth, gestation, and lactation were predicted from equations adapted from the literature based on body weight, frame size, sex, and breed group. Economic inputs and outputs were computed by accounting for variable input expenses and output revenues associated with animal performance and fixed costs associated with range management. Simulated measures of system performance included measures of energy conversion, break-even prices, and profit.