Temporal patterns in growth and survival of the round goby Neogobius melanostomus.

Monthly, overwinter and annual instantaneous growth rates for round goby Neogobius melanostomus were calculated with maximal growth occurring in July and August and almost no growth observed between ice appearance (October) and melt (March). Annual absolute growth rates averaged 27·3 ± 1·9 mm for males and 19·8 ± 2·4 mm for females. The most parsimonious Cormack-Jolly-Seber model indicated that both the survival and recapture probabilities were dependent on sampling date, but not sex. Survival estimates remained high throughout the 13 month study with a median weekly survival probability of 0·920 (25 and 75% quartiles: 0·767 and 0·991), an overwinter survival probability of 99% and an annual survival rate of 67%. Survival probabilities were lowest for both sexes near the completion of the N. melanostomus reproductive season in July and August which supports existing evidence of higher mortality after reproduction, while challenging the paradigm that male N. melanostomus suffer comparatively higher mortality as a result of reproduction than females. Evidence indicating that growth and mortality rates are highest at the end of the reproductive season not only highlights seasonal variability in N. melanostomus natural history, but may also guide the control of this invasive species to periods when they are most vulnerable.

Pharmacokinetics of dirlotapide in the dog.

An overview of the pharmacokinetics of dirlotapide in beagle dogs is presented. The following mean parameters were observed after a 0.3-mg/kg i.v. dose of dirlotapide: plasma clearance of 7.8 mL/min/kg and volume of distribution of 1.3 L/kg. Following single oral doses of 0.05, 0.3, and 1.0 mg/kg to fed dogs and 0.3 mg/kg to fasted dogs using the commercial formulation, mean C(max) of 7.5, 46, 97, and 31 ng/mL, respectively, were observed at mean t(max) of 0.8-2.0 h. AUC and C(max) increased with increasing dose, but not proportionally. Oral bioavailability was 22-41%. Exposure, as reflected by AUC, was 54% higher in the fed than fasted state. In a 14-day repeated-dose study (0.3 mg/kg dose), the mean accumulation ratio was 3.7. In a 3-month study at doses of 0.4-2.5 mg/kg, accumulation ratios ranged from 2.0 to 6.7 at day 29 and from 1.3 to 4.1 at day 87. In summary, dirlotapide exhibited low clearance, low first-pass metabolism, moderate volume of distribution, low-to-moderate oral bioavailability, a modest food effect, and variable accumulation. Large interanimal variability in systemic exposure was noted for all routes and doses, but there were no consistent sex differences.

Absorption, distribution, metabolism, and excretion of dirlotapide in the dog.

Three once-daily oral doses of 0.2 mg/kg [(14)C]dirlotapide were administered to beagle dogs to study the absorption, distribution, metabolism, and excretion of dirlotapide. Mean (14)C recovered at 2.5 and 4.5 h after the last dose was 90%. Mean (14)C in urine, bile, and feces was <1%, 1.7%, and 56% of the dose, respectively. In tissues, 26% of the (14)C dose was present in the gastrointestinal tract, 6.0% in liver, and <1% each in kidney, gall bladder, heart, and brain. To further characterize drug disposition, a single 2.5-mg/kg oral dose of [(14)C]dirlotapide was administered to beagle dogs. More than 84% of the dose had been eliminated by 72 h in feces, with 21% of the dose present in feces as parent dirlotapide. Less than 1% of the dose was excreted in urine. In bile collected during the first 24-h postdose from three dogs, 32% and 11% of the (14)C dose was present in samples from male and female dogs, respectively. Based upon metabolite profiling of plasma, excreta, and bile samples, dirlotapide was extensively metabolized to more than 20 metabolites. Biliary/fecal excretion and the potential for enterohepatic recycling of metabolites are suggested.

Histopathological and behavioral characterization of a novel cervical spinal cord displacement contusion injury in the rat.

Cervical contusive trauma accounts for the majority, of human spinal cord injury (SCI), yet experimental use of cervical contusion injury models has been limited. Considering that (1) the different ways of injuring the spinal cord (compression, contusion, and transection) induce very different processes of tissue damage and (2) the architecture of the spinal cord is not uniform, it is important to use a model that is more clinically applicable to human SCI. Therefore, in the current study we have developed a rat model of contusive, cervical SCI using the Electromagnetic Spinal Cord Injury Device (ESCID) developed at Ohio State University (OSU) to induce injury by spinal cord displacement. We used the device to perform mild, moderate and severe injuries (0.80, 0.95, and 1.1 mm displacements, respectively) with a single, brief displacement of <20 msec upon the exposed dorsal surface of the C5 cervical spinal cord of female (180-200 g) Fischer rats. Characterization of the model involved the analysis of the temporal histopathological progression of the injury over 9 weeks using histochemical stains to analyze white and gray mater integrity and immunohistochemistry to examine cellular changes and physiological responses within the injured spinal cord. Accompanying the histological analysis was a comprehensive determination of the behavioral functionality of the animals using a battery of motor tests. Characterization of this novel model is presented to enable and encourage its future use in the design and experimental testing of therapeutic strategies that may be used for human SCI.

BAG-1 expression in normal and neoplastic endometrium.

OBJECTIVE: BAG-1 has anti-apoptotic actions and is known to bind BCL-2 and steroid receptors. High levels of BAG-1 have been implicated as a prognostic indicator in breast cancer. Whether this observation can be generalized to endometrial cancer remains unknown. METHODS: IRB permission was obtained for use of human discarded tissue. Immunohistochemical analyses were performed on: proliferative endometrium (PEM, 6), secretory endometrium (SEM, 28), "low-grade" neoplastic lesions (complex atypical hyperplasia and grade 1 endometrial adenocarcinomas) (19), and "high-grade" cancers (grade 2 and 3 endometrial adenocarcinomas) (13). The level of total BAG-1 and its isoforms was evaluated by Western blot in lysates from Ishikawa cells (grade 1), MFE 296 cells (grade 2), and SK-UT(2) cells (grade 3). RESULTS: The proportion of "high-grade" cancers with positive cytoplasmic staining for BAG-1 was higher than that of secretory endometrium (P = 0.006). Additionally, the proportion of specimens with positive staining for nuclear BAG-1 expression was significantly higher among high-grade carcinoma specimens compared to secretory specimens (P = 0.009). A high proportion (91%) of all specimens were positive for BCL-2, limiting the ability to subcategorize the other variables analyzed. There was no relationship between positive nuclear BAG-1 expression and either estrogen receptor (ER) or progesterone receptor (PR) expression. BAG-1 was expressed in the three cell lines evaluated and total BAG-1 level was not different among the different cell lines. CONCLUSION: BAG-1 is expressed in the endometrium. High-grade cancers stain more frequently than secretory endometrium for both cytoplasmic and nuclear BAG-1 expression, perhaps indicating an association between expression of BAG-1 and prognosis.

The effect of treating alfalfa with Lactobacillus buchneri 40788 on silage fermentation, aerobic stability, and nutritive value for lactating dairy cows.

Lactobacillus buchneri 40788 and enzymes (beta-glucanase, alpha-amylase, xylanase, and galactomannase) were applied to chopped alfalfa (39% DM) to study their effects on the fermentation and nutritive value of the silage. Alfalfa was treated with nothing, or L. buchneri 40788, for a final application rate of 1 x 10(5), 5 x 10(5), or 1 x 10(6) cfu/g of fresh forage and ensiled in laboratory silos for 2, 4, 8, and 56 d. Treatment with L. buchneri 40788 had few effects on the end products of fermentation through 8 d of ensiling. However, after 56 d of ensiling, treated silages had a higher pH (4.55 vs. 4.38) and higher concentrations of acetic acid (6.40 vs. 4.24%), propionic acid (0.18 vs. 0.06%), and ammonia-N (0.35 vs. 0.29%) when compared to untreated silage. Lactic acid was also numerically lower in treated (3.51%) than untreated (4.12%). Silages treated with the moderate and highest dose of L. buchneri 40788 also resulted in greater recoveries of DM than did untreated silage. Alfalfa (43% DM) was also untreated or treated with a commercial application of L. buchneri 40788 (4 x 10(5) cfu/g, a commercial dose) in farm-scale bag silo. Holstein cows were fed a diet comprised of 32% untreated or treated alfalfa silage, 11% corn silage, 5% chopped alfalfa hay, and 52% of concentrate (DMB) for a 6-wk treatment period. Dry matter intake and milk composition were unaffected by treatment, but cows fed silage treated with L. buchneri 40788 produced 0.8 kg more milk than did cows fed untreated silage. Treated silage had a higher concentration of acetic acid (5.67 vs. 3.35%) but lower lactic acid (3.50 vs. 4.39%) than untreated silage. When exposed to air, the total mixed ration containing treated alfalfa silage remained stable for 100 h, whereas the ration containing untreated silage spoiled after 68 h. Treating alfalfa silage with L. buchneri 40788 increased the concentration of acetic acid, and when the silage was combined into a total mixed ration and fed to lactating cows, it improved the aerobic stability of the ration and increased milk production.

Predictors of progression of HRCT diagnosed fibrosing alveolitis in patients with rheumatoid arthritis.

BACKGROUND: Fibrosing alveolitis (FA) is the most serious pleuropulmonary extra-articular feature of rheumatoid arthritis (RA). Features that predict progression of FA in patients with RA have not yet been determined. OBJECTIVE: To identify clinical features that predict progressive FA in patients with RA. METHODS: An unselected cohort of 29 patients with RA and FA confirmed by high resolution computed tomography (HRCT) were studied prospectively for 24 months. Three monthly clinical assessment, four monthly pulmonary function tests, and yearly HRCT scanning was undertaken on these patients. Progressive FA was defined as >15% fall in carbon monoxide transfer factor (TLCO) with evidence of increasing FA on HRCT or death as a result of FA. RESULTS: During 24 months of follow up 10/29 (34%) patients had progressive FA. Progression on HRCT was seen as acute ground glass exacerbations or increasing reticular pattern lung involvement. Progressive FA was associated with the presence of bibasal crackles (p=0.041), TLCO (p=0.001), and extent (p=0.026) and distribution (p=0.031) of lung involvement on HRCT at initial presentation. When multiple logistic regression was used, only TLCO remained significant. Receiver operator curve analysis was employed to identify presenting TLCO of progressive FA. A TLCO <54% of the predicted value demonstrated 80% sensitivity and 93% specificity in predicting progressive FA. CONCLUSIONS: A TLCO <54% of the predicted value is a highly specific predictor of disease progression.

Investigation of the chronic pulmonary effects of low-dose oral methotrexate in patients with rheumatoid arthritis: a prospective study incorporating HRCT scanning and pulmonary function tests.

OBJECTIVE: Methotrexate has a well-recognized side-effect of acute hypersensitivity pneumonitis. There is concern about whether chronic pulmonary toxicity can occur with methotrexate treatment. Our objective was to compare chest high-resolution computed tomography (HRCT) findings and serial pulmonary function tests in rheumatoid arthritis (RA) patients on methotrexate with findings for a control group of patients with RA who were not being treated with methotrexate. METHODS: Study patients had an initial chest radiograph, full pulmonary function tests and chest HRCT. Pulmonary function tests were then performed regularly over a 2-yr period. RESULTS: Fifty-five RA patients on methotrexate and 73 control patients with RA were enrolled for the study. Mean dose of methotrexate was 10.7 mg/week (S.D. 2.5 mg/week) and mean duration of treatment at entry into the study was 30 (20) months. Twenty per cent of patients with RA treated with methotrexate had pulmonary fibrosis (PF) on initial HRCT compared with 23% in the control group. When the patients with and without PF were compared, there was no statistical difference in the duration (mean difference -4.18 months, P=0.237) or dose (mean difference -0.8 mg/week P=0.52) of methotrexate therapy. Mean changes after 2 yr in forced expiratory volume, forced vital capacity, diffusion capacity for carbon monoxide and residual volumes were not different in the methotrexate group compared with the control group. CONCLUSION: There is no evidence to suggest clinically, from HRCT assessment or serial pulmonary function tests, that low-dose methotrexate is associated with chronic interstitial lung disease.

Fibrosing alveolitis in patients with rheumatoid arthritis as assessed by high resolution computed tomography, chest radiography, and pulmonary function tests.

BACKGROUND: Fibrosing alveolitis (FA) is a common and serious complication of rheumatoid arthritis (RA). Before the availability of high resolution computed tomographic (HRCT) scanning, it was difficult to diagnose accurately without recourse to biopsy. Prospective studies have reported a prevalence of interstitial lung disease (ILD) of 19-44%. The term ILD used by these authors encompasses a variety of appearances on HRCT scans. This prospective study used HRCT scanning to determine the true prevalence of FA in hospital outpatients with RA, and to study associated clinical characteristics. METHODS: One hundred and fifty consecutive patients with RA were selected from a hospital outpatient department, irrespective of the presence or absence of chest disease. All underwent a detailed clinical assessment, chest HRCT scanning, and conventional chest radiography within 4 weeks of full pulmonary function tests. RESULTS: Seventy percent of patients were current or reformed cigarette smokers. Twenty eight (19%) had FA, most frequently of reticular pattern, and 12 of this group (43%) also had emphysematous bullae. None of the previously suggested risk factors for developing FA were confirmed. Fifty four percent of patients with HRCT evidence of FA had bilateral basal chest crackles, 82% had a reduced carbon monoxide transfer factor (TLCO), 14% had restrictive pulmonary function tests, and 14% had bilateral chest radiographic signs of FA. CONCLUSIONS: HRCT evidence of FA was present in 19% of hospital outpatients with RA. Abnormalities on chest examination or on full pulmonary function tests, even without restrictive changes or chest radiographic abnormalities, should prompt physicians to request a chest HRCT scan when investigating dyspnoea in patients with RA.

Heavy cigarette smoking is strongly associated with rheumatoid arthritis (RA), particularly in patients without a family history of RA.

OBJECTIVES: To investigate the potential relation between cumulative exposure to cigarette smoking in patients with or without rheumatoid arthritis (RA) and a positive family history of the disease. METHODS: 239 outpatient based patients with RA were compared with 239 controls matched for age, sex, and social class. A detailed smoking history was recorded and expressed as pack years smoked. Conditional logistic regression was used to calculate the association between RA and pack years smoked. The patients with RA were also interviewed about a family history of disease and recorded as positive if a first or second degree relative had RA. The smoking history at the time of the study of the patients with RA with or without a family history of the disease was compared directly with that of their respective controls. Patients with RA with or without a family history of the disease were also compared retrospectively for current smoking at the time of disease onset. RESULTS: An increasing association between increased pack years smoked and RA was found. There was a striking association between heavy cigarette smoking and RA. A history for 41-50 pack years smoked was associated with RA (odds ratio (OR) 13.54, 95% confidence interval (95% CI) 2.89 to 63.38; p<0.001). The association between ever having smoked and RA was modest (OR 1.81, CI 1.22 to 2.19; p=0.002). Furthermore, cigarette smoking in the patients with RA without a positive family history of RA was more prevalent than in the patients with a positive family history of RA for ever having smoked (72% v 54%; p=0.006), the number of pack years smoked (median 25.0 v 4.0; p<0.001), and for smoking at the time of disease onset (58% v 39%; p=0.003). CONCLUSIONS: Heavy cigarette smoking, but not smoking itself, is strongly associated with RA requiring hospital follow up and is markedly more prevalent in patients with RA without a family history of RA.

Advanced practice issues: results of the ONS Advanced Practice Nursing survey.

PURPOSE/OBJECTIVES: To ascertain the critical issues in current advanced practice nurse (APN) roles in oncology. DESIGN: Descriptive. SETTING: National. SAMPLE: 368 Oncology Nursing Society (ONS) APNs in oncology practice. METHODS: Subjects completed an 11-page self-administered questionnaire comprised of 62 multiple-choice and open-ended questions. Subjects were asked to identify level of importance for ONS to address selected issues in each section. MAIN RESEARCH VARIABLES: Demographic information and APN issues regarding practice, outcomes, prescriptive authority, reimbursement, education, continuing education, licensure and certification, legislation, and challenges facing oncology APNs. FINDINGS: The majority of APNs were nurse practitioners working in a hematology/oncology practice in an urban setting providing direct patient care. Priority practice issues were lack of agreement among state boards of nursing related to privileges, lack of understanding of the role by patients and healthcare professionals, and lack of an APN definition. Important APN outcomes were symptom management, quality of life, patient/family satisfaction, and cost of care. Priority educational topics were oncology disease management, pharmacology, advanced physical assessment, and reimbursement. Challenges facing oncology APNs were lack of an APN definition, reimbursement issues, documentation of outcomes, prescriptive authority, variance in education, merging of current roles, certification, loss of cancer specialty, and second licensure. CONCLUSIONS: Numerous APN issues continue to be unresolved. APN outcomes research is needed to validate the oncology APN role in cancer care. IMPLICATIONS FOR NURSING PRACTICE: Survey results and specific recommendations have been forwarded to the ONS Steering Council and Board of Directors for implementation decisions.

Development of a home-based family caregiver cancer education program.

INTRODUCTION: This article describes a home-based educational program developed specifically for family caregivers of cancer patients who receive hospice and home care. The overall aim of this educational program is to specifically address family caregivers' needs for acquisition of necessary knowledge and skills to meet the physical and psychosocial demands associated with caring for a patient with advanced cancer. PROGRAM DEVELOPMENT: Originally, components of this program were offered in a small group discussion format within hospital and community settings. The educational program was transformed to accommodate the unique needs and constraints of homebound family caregivers who have very limited time and/or opportunities for support and education outside of the home. The program is comprised of educational modules that provide hospice and home care professionals with written and audiovisual materials designed to facilitate brief, structured, educational encounters with family caregivers in the home setting. DISCUSSION: Two hundred thirty-seven educational module kits were distributed to professionals affiliated with twenty-four home care and hospice agencies in the Greater Philadelphia area. Results of a telephone survey designed to elicit evaluation data from professional staff members who had used the educational modules are presented. Limitations, plans for future program evaluation, cost implications, and implementation recommendations related to this educational program are described.

Effect of erythorbic acid on cooked color in ground beef.

Consumers often use the color of cooked ground beef as an indicator of doneness. For safety reasons, it is recommended that the center of ground beef products be heated to 71°C. In some instances beef may appear done before reaching 71°C, a condition termed premature browning (PMB). Ground beef (15% fat), with added erythorbic acid (ERY) at 0.04 and 0.06% was formed into patties, wrapped in oxygen permeable film, and stored in the dark at 4°C. Patties were stored for either 10 h or 58 h and then cooked to internal end point temperatures of 60, 66, 71 or 77°C. Internal cooked color L(∗), a(∗) and b(∗) values were measured. For beef patties stored 10 h, there was no effect of ERY on internal cooked color. After 58 h storage, ground beef with 0.04 and 0.06% ERY had higher a(∗) values than controls at 60°C (P<0.05). Beef with 0.04% ERY cooked to an internal temperature of 66°C had higher a(∗) values than 0.06% ERY and controls (P<0.05). There was no effect of ERY on color of beef patties cooked to 71 or 77°C. The presence of 0.04% ERY in ground beef patties stored 58 h appeared to maintain red color at internal temperatures of 60 and 66°C.

Effect of dietary α-tocopherol supplementation on color and lipid stability in pork.

Myoglobin and lipid oxidation are major causes of quality deterioration in fresh pork. A process to enhance color and lipid stability would prove valuable to the pork industry given the current trend of centralized packaging and distribution to retail markets. Our objective was to determine the effects of dietary α-tocopherol (α-Toc) supplementation on color and lipid stability in ground pork, and loin chops stored in modified atmosphere packaging (MAP). Yorkshire crossbred pigs (n=20) were randomized into two groups and fed diets containing 48 (CON) or 170 mg α-Toc acetate/kg feed (VIT-E) for 6 weeks before slaughter. Plasma α-Toc concentration was measured weekly. Post-slaughter, Boston butt shoulders were ground, formed into patties with or without 1.5% salt, and stored fresh at 4°C for 0, 2, 4, or 6 days, and frozen at -20°C for 45 or 90 days. Pork loin chops were packaged aerobically and stored at 4°C for 0, 2, 4 or 6 days, or in MAP at 4°C for 7, 10 or 13 days prior to Hunter L*,a*,b* and TBARS analyses. α-Toc concentration of longissimus dorsi, psoas major, biceps femoris, semimembranosus and semitendinosus muscles was determined. Plasma α-Toc was greater (P<0.05) in VIT-E animals compared with CON and α-Toc concentrations were greater (P<0.05) in all VIT-E muscles compared with CON. TBARS values of both fresh and salted patties were less in VIT-E than in CON meat following 6 days at 4°C; VIT-E TBARS of salted patties were less (P<0.05) after 45 days at -20°C compared with CON. α-Toc supplementation did not influence (P>0.05) color of aerobically packaged or MAP chops, or of fresh or salted pork patties. α-Toc supplementation reduced TBARS formation in fresh and salted pork but had no significant impact on color.

Effect of aldehyde lipid oxidation products on myoglobin.

The effects of aldehyde lipid oxidation products on myoglobin (Mb) were investigated at 37 degrees C and pH 7.2. Oxymyoglobin (OxyMb) oxidation increased in the presence of 4-hydroxynonenal (4-HNE) compared to controls (P < 0.05). Preincubation of metmyoglobin (MetMb) with aldehydes rendered the heme protein a poorer substrate for enzymatic MetMb reduction compared to controls, and the effect was inversely proportional to preincubation time; unsaturated aldehydes were more effective than saturated aldehydes (P < 0.05). The order of MetMb reduction as affected by preincubation was control > hexanal > heptanal > octanal > nonanal = decanal = hexenal > heptenal = octenal > nonenal = decenal = 4-HNE (P < 0.05). Preincubation of MetMb with 4-HNE enhanced the subsequent ability of the heme protein to act as a prooxidant in both liposomes and microsomes when compared to controls (P < 0.05); the effect was reduced in microsomes containing elevated concentrations of alpha-tocopherol (P < 0.05). MetMb preincubation with mono-unsaturated aldehydes enhanced the catalytic activity of MetMb to a greater degree than saturated aldehydes (P < 0.05). These results suggest that aldehyde lipid oxidation products can alter Mb stability by increasing OxyMb oxidation, decreasing the ability of MetMb to be enzymatically reduced and enhancing the prooxidant activity of MetMb.

Raised pulmonary artery pressures measured with Doppler echocardiography in rheumatoid arthritis patients.

OBJECTIVE: To study the prevalence of echocardiographic abnormality and pulmonary hypertension in an unselected population of patients with rheumatoid arthritis (RA). METHOD: One hundred and forty-six RA patients, irrespective of cardiopulmonary symptoms, were assessed clinically and by echocardiography, including pulmonary artery pressure measurement, ECG, pulmonary function tests and high-resolution computed tomography scanning of the thorax. RESULTS: Two-dimensional echocardiography demonstrated significant cardiac disease in the form of reduced left ventricular ejection fraction (<64%) in 9% of patients, moderate mitral regurgitation in 4%, aortic stenosis in 4%, aortic regurgitation in 3% and Valsalva sinus rupture in 0.7%. In addition, 1% had detectable pericardial effusions. Thirty-one per cent of the RA patients had an estimated pulmonary artery systolic pressure of 30 mmHg or more, and 21% of all the RA patients had pulmonary hypertension without significant cardiac disease or lung disease evident on pulmonary function testing. CONCLUSIONS: A wide and frequent variety of echocardiographic cardiac abnormalities may be found in an unselected population of patients with RA. Using Doppler echocardiography, we have found pulmonary hypertension secondary to lung disease in 6% of the population and a larger than expected prevalence of mild primary pulmonary hypertension in patients with RA. The latter observation may be relevant to the high incidence of cardiovascular-related deaths observed in patients with RA