Diverticular disease in Scotland: 2000-2010.

AIM: Symptomatic diverticular disease (DD) may be increasing in incidence in western society particularly in younger age groups. This study aimed to describe hospital admission rates and management for DD in Scotland between 2000 and 2010. METHOD: Data were obtained from the Scottish Morbidity Records (SMR01). The study cohort included all patients with a hospital admission and a primary diagnosis of DD of the large intestine (ICD-10 primary code K57). RESULTS: Scottish NHS hospitals reported 90 990 admissions for DD (in 87 314 patients) from 2000 to 2010. The annual number of admissions increased by 55.2% from 6591 in 2000 to 10,228 in 2010, an average annual increase per year of 4.5%. Most of the increase attributable to DD was due to elective day cases (3618 in 2000; 6925 in 2010) a likely consequence of a greater proportion of the population accessing colonoscopy over that time period. There was an 11% increase in inpatient admissions (2973-3303), 60% of these patients being women. Admissions in younger age groups increased proportionally in the later years of the study, and there was an association between DD admissions and greater deprivation. Despite an increase in complicated DD from 22.9% in 2000 to 27.1% in 2010 and a 16.8% increase in emergency inpatient admissions, the rate of surgery fell during the period of study. CONCLUSION: This report supports findings of other population-based studies of western countries indicating that DD is an increasing burden on health service resources, particularly in younger age groups.

Comparison of mortality following hospitalisation for ulcerative colitis in Scotland between 1998-2000 and 2007-2009.

BACKGROUND: Scottish nationwide linkage data from 1998 to 2000 demonstrated high 3-year mortality in patients hospitalised with ulcerative colitis (UC). AIM: To compare 3-year mortality, and factors related to mortality, in Scottish patients hospitalised with UC between 1998-2000 and 2007-2009. METHODS: The Scottish Morbidity Records and linked datasets were used to assess 3-year mortality, standardised mortality ratio (SMR) and multivariate analyses of factors associated with 3-year mortality. The 3-year mortality was determined after four admission types: surgery-elective or emergency; medical-elective or emergency. Age-standardised mortality rates (ASR) were used to compare mortality rates between periods. RESULTS: Ulcerative colitis admissions increased from 10.6 in Period 1 to 11.6 per 100 000 population per year in Period 2 (P = 0.046). Crude and adjusted 3-year mortality fell between time periods (crude 12.2% to 8.3%; adjusted OR 0.59, CI 0.42-0.81, P = 0.04). Adjusted 3-year mortality following emergency medical admission (OR 0.58, CI 0.39-0.87, P = 0.003) and in patients >65 years (38.8% to 28.7%, P = 0.02) was lower in Period 2. The SMR in period 1 was 3.04 and 2.96 in Period 2. Directly age-standardised mortality decreased from 373 (CI 309-437) to 264 (CI 212-316) per 10 000 person-years. On multivariate analysis, increasing age (50-64 years OR 7.11 (CI 2.77-18.27, P < 0.05); 65-74 years OR 14.70 (CI 5.65-38.25 P < 0.05); >75 years OR 46.42 (CI 18.29-117.78, P < 0.001) and co-morbidity (OR 3.02, CI 1.72-5.28, P < 0.001) were significantly associated with 3-year mortality in Period 2. CONCLUSIONS: Comparisons of crude and adjusted mortality rates suggest significant improvement in outcome over the last decade - however, mortality remains high, and older age and co-morbidity are important predictors of outcome.

Nationwide linkage analysis in Scotland to assess mortality following hospital admission for Crohn's disease: 1998-2000.

BACKGROUND: Although population-based studies of patients with Crohn's disease (CD) suggest only a modestly increased mortality, recent data have raised concerns regarding the outcome of CD patients requiring hospitalisation. AIM: To determine the mortality and contributory factors in 1595 patients hospitalised for CD in Scotland between 1998 and 2000. METHODS: The Scottish Morbidity Records database and linked datasets were used to assess longitudinal patient outcome, and to explore associations between 3-year mortality and age, sex, comorbidity, admission type and social deprivation. The standardised mortality ratio (SMR) at 3 years from admission was calculated with reference to the Scottish population. RESULTS: The SMR was 3.31 (95% confidence interval 2.80-3.89). This was increased in all patients, other than those <30 years at presentation, and was highest in patients aged 50-64 years (SMR 4.84 [3.44-6.63]). On multivariate analysis, age >50, admission type, comorbidity, social deprivation and length of admission were significantly associated with mortality. Other than age, admission type was the strongest factor predictive of death. Three-year crude mortality was 0.3% for elective surgical, 8.7% for emergency surgical, 8.3% for elective nonsurgical and 12.7% for emergency nonsurgical admission (P < 0.001). CONCLUSIONS: The study demonstrates high mortality rates in patients hospitalised during 1998-2000 for CD, especially in patients over 50. Elective surgery is associated with lower mortality than emergency surgery or medical therapy. Further study is needed to determine whether these patterns have changed following the introduction of biological treatment.

Nationwide linkage analysis in Scotland implicates age as the critical overall determinant of mortality in ulcerative colitis.

BACKGROUND: Recent data associated higher mortality with medical rather than surgical intervention in patients with ulcerative colitis who require hospitalization. AIM: To examine factors influencing UC-related mortality in Scotland. METHOD: Using the national record linkage database 1998-2000, 3-year mortality was determined after four admission types: colectomy-elective or emergency; no colectomy-elective or emergency. RESULTS: Of 1078 patients, crude 3-year mortality rates were: colectomy elective 5.6% (n = 177) and emergency 9.0% (100); no colectomy elective 9.8% (244) and emergency 16.0% (557). Using elective colectomy as reference, multivariate analysis [OR (95% CI)] showed that admission age >50 years [OR 5.46 (2.29-11.95)], male gender [OR 1.92 (1.23-3.02)], comorbidity [OR 2.2 (1.38-3.51)], length of stay >15 days [OR 2.04 (1.08-3.84)] and prior IBD admission [OR 1.66 (1.06-2.61)] were independently related to mortality. Age was the strongest determinant. No patient <30 years died. Mortality of patients aged <50 years [10/587 (1.7%)] was significantly lower than mortality of those aged 50-64 years [26/246 (10.6%)] (chi(2) = 32.91; P < 0.0000001) and >65 [96/245 (39.2%)] (chi(2) = 218.2; P < 0.0000001). For those patients aged more than 65 years, mortality in the four groups was 29.4%, 33.3%, 28.1% and 44.7%- all greater than expected in the Scottish population on assessment of standardized mortality ratios. CONCLUSION: Hospital admission in UC patients >65 is associated with high mortality. Management strategies should consider this by treatment in specialist units, early investigation, focused medical treatment and earlier surgical referral.

The SCAR-3 study: 5-year adhesion-related readmission risk following lower abdominal surgical procedures.

OBJECTIVE: The Surgical and Clinical Adhesions Research (SCAR) and SCAR-2 studies demonstrated that the burden of adhesions following lower abdominal surgery is considerable and appears to remain unchanged despite advances in strategies to prevent adhesions. In this study, we assessed the adhesion-related readmission risk directly associated with common lower abdominal surgical procedures, taking into account the effect of previous surgery, demography and concomitant disease. METHODS: Data from the Scottish National Health Service medical record linkage database were used to assess the risk of an adhesion-related readmission following open lower abdominal surgery during April 1996-March 1997. RESULTS: Patients undergoing lower abdominal surgery (excluding appendicectomy) had a 5% risk of readmission directly related to adhesions in the 5 years following surgery. Appendicectomy was associated with a lower rate of readmission (0.9%), but contributed over 7% of the total lower abdominal surgery patient readmission burden. Panproctocolectomy (15.4%), total colectomy (8.8%) and ileostomy surgery (10.6%) were associated with the highest risk of an adhesion-related readmission. Overall, the risk of readmission was doubled in patients who had undergone abdominal or pelvic surgery within 5 years of the incident operation. A higher risk of readmission was also recorded in patients aged < 60 years compared with those aged > or = 60 yrs. The effect of gender was assessed. However, as the surgical codes used were found to be skewed towards women, these data have not been reported. Readmission risk was slightly higher in patients with concomitant peritonitis compared with patients without peritonitis. In contrast, Crohn's disease had no effect on risk. Patients with colorectal cancer had a lower risk of adhesion formation. However, this may have been due to the type of surgery performed in this patient group. CONCLUSION: The identification of high-risk patient subgroups may assist in effectively targeting adhesion-prevention strategies and the proffering of preoperative advice on adhesion risk.

Colorectal surgery: the risk and burden of adhesion-related complications.

OBJECTIVES: Adhesions are associated with serious medical complications. This study examines the real-time burden of adhesion-related readmissions following colorectal surgery and assesses the impact of previous surgery on adhesion-related outcomes. PATIENTS AND METHODS: The study used data from the Scottish National Health Service Medical Record Linkage Database to identify three cohorts of patients who had undergone open colorectal surgery during the financial years 1996-97, 1997-98 and 1998-99. Each cohort was followed up for at least 2 years and the number and category of adhesion-related readmissions was recorded. The influence of any previous operations on adhesion-related readmissions was also determined by performing a subanalysis within the 1996-97 cohort of patients who had no record of abdominal surgery within either the previous 5 or 15 years. The relative risk of adhesion-related readmissions was also assessed. RESULTS: In the 1996-97 cohort, 9.0% of patients were readmitted within a year after surgery; 2.1% had complications directly related to adhesions and 6.9% had complications that were possibly related. After 4 years, 19.0% of patients were readmitted for reasons directly or possibly related to adhesions. Many patients were readmitted on more than one occasion and the relative risk of adhesion-related complications was 29.7 per 100 initial procedures over 4 years. In the subgroups that had no record of abdominal surgery within the previous 5 or 15 years, the relative risks of adhesion-related complications were 24.8% and 23.5%, respectively. There was no change in the rate of adhesion-related readmissions following colorectal surgery between 1996 and 1999. CONCLUSION: Colorectal surgery is associated with a considerable rate of adhesion-related readmissions. Preventative measures should be considered to reduce this risk.

Adhesion-related readmissions following gynaecological laparoscopy or laparotomy in Scotland: an epidemiological study of 24 046 patients.

BACKGROUND: Gynaecological laparotomies are associated with considerable adhesion-related burdens; however, few data are available concerning laparoscopic surgery. This study evaluated the epidemiology of adhesion-related readmissions following open and laparoscopic procedures. METHODS: Records from 24,046 patients undergoing gynaecological surgery in Scottish National Health Service hospitals during 1996 were assessed retrospectively. Cohorts comprised 15,197 patients undergoing laparoscopic surgery and 8849 patients undergoing laparotomies. Adhesion-related readmission episodes (directly and possibly related) were assessed over 4 years following initial surgery and were expressed as percentages of the number of initial procedures. RESULTS: Directly adhesion-related readmissions 1 year after initial laparoscopic surgery were: in the high-risk group (adhesiolysis and cyst drainage) 1.3%; medium-risk (therapeutic and diagnostic procedures not categorized as high- or low-risk) 1.5%; and low-risk (Fallopian tube sterilizations) 0.2%. Readmissions for laparotomy following surgery on the Fallopian tubes were 0.9%, ovaries 2.1%, uterus 0.6% and vagina 0%. Readmissions occurred at reduced rates in the second, third and fourth years after surgery. Exclusion of patients who underwent surgery within the previous 5 years resulted in reduced readmission rates following laparotomy and high-risk laparoscopy. CONCLUSIONS: With the exception of laparoscopic sterilizations, open and laparoscopic gynaecological surgery are associated with comparable risks of adhesion-related readmissions.

Demonstrating the clinical and cost effectiveness of adhesion reduction strategies.

OBJECTIVE: To examine the feasibility of conducting Randomized Controlled Trials (RCT) in lower abdominal surgery to demonstrate a reduction in adhesion-related admissions following use of an adhesion reduction product, and to model the cost effectiveness of such products. METHODS: The number of patients in each limb of a RCT comparing an adhesion reduction product to a control has been estimated based on 25% and 50% reductions in adhesion-related readmissions one year after surgery, for P = 0.05 at a power of 80% and P=0.01 at a power of 90%. A cost effectiveness model based on the Surgical and Clinical Adhesions Research Group (SCAR) database has been developed which calculates the percentage reduction in readmissions required of an adhesion reduction product to return the cost of investment. It also estimates the cumulative costs of adhesion-related readmissions for lower abdominal surgery and the cost savings associated with an adhesion reduction policy using a low or high cost product. RESULTS: 7.2% of patients undergoing lower abdominal surgery will readmit due to adhesions in the first year after surgery. To demonstrate a 25% reduction in readmissions one year after surgery, it is calculated that a RCT would require between 5686 (P = 0.05, power=80%) and 7766 (P = 0.01, power = 90%) lower abdominal surgery patients followed-up for one year. A cost effectiveness analysis demonstrates that routine use of adhesion reduction products costing pound 50 per patient will payback the cost of such investment if they reduce adhesion-related readmissions by 16% after 3 years. A product costing pound 200 will need to offer a 64.1% reduction in readmissions after 3 years. For the estimated 158 000 lower abdominal surgery operations conducted in the UK each year, the cumulative costs of adhesion-related readmissions over 10 years are estimated at pound 569 Million. CONCLUSION: Demonstrating the clinical effectiveness of adhesion reduction products in the RCT setting is unlikely to be feasible due to the large number of patients required. Products costing pound 200 or more are unlikely to payback their direct costs.

Usefulness of subjective ovine milk scores: I. Associations with range ewe characteristics and lamb production.

Range ewes are commonly evaluated for milking ability by producers to determine the ewe's ability to rear lamb(s). The U.S. Sheep Experiment Station has subjectively scored (low, average, high) a ewe's milking ability within 24 h of lambing for many years. The relationship of subjective milk scores with lamb production was investigated using lambing records of Columbia (n = 1,731), Polypay (n = 1,129), Rambouillet (n = 1,704), and Targhee (n = 1,638) ewes. The incidence of high milk scores increased from less than 10% at first parity to 29 to 40% at second and greater parities. At maturity, Columbia ewes (38%) had the highest percentage of high milk scores. A positive association existed between ewe BW and her milk score at third and later parities. Ewes with high milk scores gave birth to heavier lambs (P < 0.05), whereas ewes with low milk scores were associated with lighter (P < 0.05) lambs at birth. Ewes with low milk scores weaned less (P < 0.05) total weight than ewes with better milk scores across all age groups for all breeds. Lighter weaned litter weights from ewes with low milk scores were linked to lighter birth weights and fewer weaned lambs. Differences for litter weight weaned between ewes with average and high milk scores were generally observed at 2 and 3 yr of age, when litter weights were heavier among ewes with high milk scores (P < 0.05) for all breeds. Between the ages of 1 and 3 yr, Columbia, Polypay, Rambouillet, and Targhee ewes with an average milk score weaned heavier (P < 0.05) litters (average differences of 10, 9, 13, and 12%, respectively) than ewes with low milk scores. For all breeds at all ages, individual lamb weaning weights were heavier (P < 0.05) when they were reared by ewes with high milk scores compared to lambs reared by ewes with low milk scores. Results suggest that milk score is an economically important trait in these four breeds and should be considered in management and breeding objectives; at a minimum, the incidence of low milk scores should be kept as small as possible.

Usefulness of subjective ovine milk scores: II. Genetic parameter estimates.

Genetic parameters for a subjective milk score given to ewes within 24 h of parturition were estimated to determine the usefulness of milk score as a selection trait to improve milk production, which influences total litter weight weaned. Heritability of milk score and the genetic correlation of milk score with litter weight weaned were estimated by REML separately for four sheep breeds, Rambouillet (n = 1,731), Targhee (n = 1,638), Columbia (n = 1,731), and Polypay (n = 1,129). Litter weight weaned was the total weight of lambs weaned at approximately 120 d of age under a western range production system. Observed heritability estimates for milk score at first parity were moderate and similar among breeds, ranging from 0.18 to 0.32. Heritability estimates adjusted for a binomial distribution of milk scores at first parity were high (Columbia, 0.43; Polypay, 0.35; Rambouillet, 0.50; Targhee, 0.84). Estimates of observed heritability for second-parity milk score were moderate to high, ranging from 0.23 to 0.46. Milk score at first or second parity was genetically correlated with milk score records at maturity (third parity and greater), with estimates ranging from 0.69 to 1.00. Milk score and litter weight weaned were genetically correlated at first or second parity in Rambouillet (r(g) = 1.00) and Targhee breeds (r(g) = 1.00 and 0.61, respectively), but not in the Columbia and Polypay breeds. Estimates of heritability for lifetime records for milk score ranged from 0.16 to 0.26 across breeds. Estimates of genetic correlations of annual lifetime milk score records with litter weight weaned were high (Columbia, 1.00; Polypay, 0.81; Rambouillet, 1.00; and Targhee, 0.77). Repeatability estimates for milk score were similar across breeds, 0.23 for Columbia, Rambouillet, and Targhee ewes and 0.28 for Polypay ewes. Milk score measured at first or second parity may be a good predictor of future potential milking ability. Further, milk score can be used as a selection trait to improve maternal ability for increasing litter weight weaned. The need for increasing ewe milking performance and lamb growth rate at first parity in commercial range sheep production systems may be addressed by selection for milk score at first parity.

Responses to various selection protocols for lamb production in Rambouillet, Targhee, Columbia, and Polypay sheep.

To investigate the effectiveness of four selection protocols for improving reproduction in sheep, we evaluated nine selection lines and two random-bred control lines for lamb and wool production. Results were based on 25,026 dam and 30,628 lamb records from Rambouillet (R), Targhee (T), Columbia (C), and Polypay (P) sheep collected from 1976 through 1988. Phenotypic trends over years were positive (P < .01) for most reproductive traits, body weight, wool grade (coarser grades), and lamb weaning weight in nearly all selected lines. Small positive trends for both random-bred control lines indicated there were improvements in management and(or) environment during the period. Small but significant phenotypic declines in fleece weights occurred in most lines, including controls. Substantial genetic gains (P < .01) in litter weight weaned (120 d), net reproductive rate (lambs weaned divided by ewes mated), prolificacy, body weight, and weaning weight were made in nearly all selected lines. There were also small but significant improvements in milk score in most lines. There were significant genetic declines and improvements in fleece weights; however, the average genetic change in fleece weight for lines selected for litter weight weaned was negligible. Genetic improvement in litter weight weaned was attributed approximately 37% to prolificacy, 27% to percentage of lambs weaned, 17% to lamb weaning weight, 12% to fertility, and 7% to ewe viability from breeding to lambing. On average, selection based on independent culling levels (litter weight weaned plus yearling body weight), yearling body weight, or early puberty was only 85, 67, or 59%, respectively, as effective as that based solely on litter weight weaned for improving litter weight weaned. The net value of the average (over all breeds) annual increase in production per ewe resulting from selection for litter weight weaned accumulated over 12 yr to an estimated $11.40 and $21.51 annually for genetic and phenotypic increases, respectively.

Breed effects of foster lamb and foster dam on lamb viability and growth.

The objective of this study was to compare maternal ability under natural and fostered rearing conditions in four breeds of sheep for lamb survival and growth to weaning age. Data included records from 1981 through 1991 of 24,696 lambs of four breeds, Rambouillet, Columbia, Targhee, and Polypay, reared by their natural dam, and 720 records of lambs fostered within their breed or across breeds. The majority (94%) of the foster lambs were from multiple-birth litters and were approximately .5 kg lighter than lambs reared by their natural dams (P < .05). Viability up to 3 wk of age was influenced by breed of foster dam; lambs reared by Polypay dams had the highest viability (96%) and lambs reared by Targhee dams the lowest (81%). Targhee dams were less successful in rearing foster lambs (75%) to weaning than the other breeds studied (average 84%). The lower viability of Targhee-reared foster lambs could not be explained by lower birth weights of foster lambs, increased starvation, or lower milk scores for Targhee dams. Although there were breed differences in weaning weights at 120 d of age, the foster lambs were lighter but the ranking by breed did not change. These results suggest that there are small breed differences in maternal ability for a ewe to raise her own lamb or foster lamb(s), except for the Targhee ewe, which has a lower success in rearing a foster lamb. Management practices to reduce the mortality rate of foster lambs should be investigated.(ABSTRACT TRUNCATED AT 250 WORDS)

Ten-year linear trends in reproduction and wool production among inbred and noninbred lines of Rambouillet, Targhee, and Columbia sheep.

To investigate the value of creating inbred lines for genetic improvement of sheep, 54 inbred, 1 randombred control, and 3 noninbred control lines were evaluated for lamb and wool production. Results were based on 19,438 dam and 23,625 lamb records from Rambouillet (R), Targhee (T), and Columbia (C) sheep collected over 9 yr (for T and C) and 10 yr (for R), starting in 1954. Average inbreeding in the inbred lines during the period was near 25% for lambs and 20% for ewes. The general trend in inbred lines for litter weight weaned (120 d) and number weaned (net reproductive rate), per ewe exposed to breeding, was downward as inbreeding increased. Trends in fleece weight generally also were down, regardless of concomitant increases in body weight. Declines were most pronounced in two lines developed by rapid inbreeding. Reproductive merit in the R and C noninbred controls also declined, but the declines were less than those for most inbred lines. Although the T noninbred control declined in fleece weight, trends for fleece weight in the R and C controls were positive and significantly different from the negative trends in the inbred lines. For the randombred control, slight downward trends in litter weight and number weaned were less (P < .05) than those for most inbred lines, indicating genetic declines in these traits for most inbred lines. Direct selection for an index of overall phenotypic merit, recurrent selection for combining ability for overall merit, and direct selection for body type, clean fleece weight, or staple length were all ineffective in preventing a decline in reproductive merit. Ending means (last 2 yr of production) revealed that litter weight weaned in the control groups of each breed was clearly superior to that in most inbred lines. Controls also were typically superior for fleece and body weight. Not one of the 54 inbred lines was superior (P < .05) to its respective noninbred control in weight of lamb weaned or net reproductive rate. Only four of the inbred lines were superior to the noninbred controls in fleece weight. These results, after at least 23 yr of development for most lines, reflect little encouragement for the costly development of many inbred lines for the purpose of improving lamb and wool production, especially when using the above selection criteria.

Deficient nifedipine oxidation: a rare inherited trait associated with cystic fibrosis kindreds.

Previous studies have indicated that there is weak genetic linkage between the defective gene in cystic fibrosis (CFTR) and the gene encoding the nifedipine metabolizing enzyme P4503A4 which are both located on chromosome 7. To examine further this possible association, nifedipine metabolism was investigated in a group of 59 volunteers, and 17 adult cystic fibrosis patients and 37 of their relatives. In agreement with the majority of previous studies, the volunteer group showed a unimodal distribution of recoveries for the major metabolite M-II ranging from 33 to 78% excretion in 8 h. In the case of both the cystic fibrosis patients and their parents, the distribution of recoveries was shifted to the left with five out of 20 parents and three out of 11 unrelated cystic fibrosis patients showing recoveries below the range observed in the volunteer group. This poor metabolism appeared to be both reproducible and heritable and did not appear to be a consequence of mutations in the CFTR gene.

Effects of inbreeding on reproduction and wool production of Rambouillet, Targhee, and Columbia ewes.

Because of a traditional interest in inbreeding as a tool for breed improvement, it was desirable to evaluate the effects of inbreeding on the most important products of the sheep industry, lamb and wool production. The data for this study were based on 13,807 ewe and 16,470 lamb records from Rambouillet (R), Targhee (T), and Columbia (C) sheep collected over 9 or 10 yr from 54 inbred lines. Average inbreeding of the lambs and ewes involved was near 25 and 20%, respectively. The combined effects of lamb's and dam's inbreeding reduced litter weight weaned at 120 d approximately .5 kg for each percentage of increase in inbreeding in every breed. For ewes and lambs of average inbreeding, the reductions relative to noninbred ewes amounted to 12.4, 10.3, and 11.3 kg for R, T, and C, respectively. The reductions constituted declines in weight weaned per ewe of 34, 25, and 28%. Similarly, net reproduction rate (lambs weaned per ewes put into breeding) was reduced more than one percentage point for each percentage of increase in inbreeding, with net declines at average inbreeding of 31.7, 23.5, and 25.7 percentage points for each breed, respectively. These reductions were equivalent to reductions in net rate of 29, 20, and 23%. The combined effect of lamb and dam inbreeding reduced weaning weight by 3.5, 2.6, and 2.2 kg, which constituted reductions of 10, 7, and 6%, respectively. Reduced weaning weight was approximately 30% as important as reduced net reproduction rate in contributing to the decline in litter weight weaned. Effects on fleece weight were curvilinear and amounted to reductions of .35, .18, and .00 kg, respectively, at levels of average inbreeding; however, Columbia fleece weights declined rapidly at levels exceeding 20% for ewes. Potential selection differentials were reduced 16% at inbreeding levels of 25 and 20% for lambs and dams, respectively, and 62% at levels of 55 and 50%. The average economic loss per ewe in value of production was estimated at $17 for average inbreeding and as high as $36 for inbreeding approaching 50%. It seems that the use of inbreeding as a tool for improving productive merit in sheep is much more certain to be a detriment, economically and genetically, than an advantage.

Asymmetrical effects of albumin on transsynovial fluid movement.

The effect of intraarticular infusions of albumin solution on transsynovial flow was studied in healthy rabbit knee joints and compared with the effect of albumin solution perfused through the synovial microcirculation. Increasing intravascular albumin levels enhanced fluid absorption from the joint cavity, whereas increasing intraarticular albumin levels reduced the absorption rate. The slope of intraarticular pressure-versus-absorption rate plots was reduced by albumin in proportion to the reduction in fluidity (1/viscosity). When joint pressure was held constant, the transsynovial absorption rate was reduced by albumin in excess of the fluidity reduction and even reversed to filtration into the joint cavity. Thus intraarticular albumin acts by a dual mechanism, namely by increasing synovial interstitial fluid viscosity and by exerting a peri-capillary oncotic pressure. However, the latter effect was much less than that of intravascular albumin. Reasons for this are discussed.

Lifetime production of 1/4 and 1/2 Finnsheep ewes from Rambouillet, Targhee and Columbia dams as affected by natural attrition.

Lifetime production of first-generation 1/4 and 1/2 Finnsheep crossbred ewes from Rambouillet (R), Targhee (T) and Columbia (C) dams was compared with that from randomly selected purebred R, T and C ewes. All 1,190 ewes, representing nine breed groups, were managed under range conditions and mated annually to Suffolk rams. Lifetime production was evaluated as the total lamb and total wool production per ewe from the time each entered the breeding flock at 7 mo of age through the period each remained in the flock (potentially seven producing years). Culling was for debilitating unsoundness only. The study was designed to determine the average lifetime production per breed group as affected by natural ewe attrition. Orphan-reared lambs were not included in lamb production nor were foster lambs, except those actually born in and reared by the groups. Differences among pooled breed groups (1/4 Finns, 1/2 Finns and purebreds) were not significant for average final age in the flock (5.1, 5.1 and 4.9 yr, respectively), but differences were significant (P less than .01) for lifetime lamb and wool production. Average lifetime fleece weights of 1/4 and 1/2 Finn ewes were only 95 and 82% as high, respectively, as those of purebreds. However, 1/4 and 1/2 Finn ewes had 34 and 46%, respectively, higher numbers of lambs weaned (at 130 d) and 30 and 38% higher total weight of lamb weaned than purebreds.(ABSTRACT TRUNCATED AT 250 WORDS)

Relation between trans-synovial flow and plasma osmotic pressure, with an estimation of the albumin reflection coefficient in the rabbit knee.

The volume of synovial fluid in a joint correlates inversely with plasma colloid osmotic pressure (COP). The inferred influence of plasma osmotic forces on trans-synovial flow was investigated directly here, in isolated perfused hindquarters of sixteen rabbits. Flow of intra-articularly infused Krebs solution across the synovial lining of the cannulated knee was recorded at controlled intra-articular pressure (18 cmH2O). Colloid osmotic pressure in the synovial microcirculation was varied by perfusion with oxygenated red cells resuspended in albumin solution or plasma from an extra-corporeal system at constant perfusion pressure. Studies in vitro showed that the COP versus concentration curve for commercial bovine albumin samples was variable and not reliably described by a widely used polynomial. The rate of trans-synovial absorption Qs was a positive linear function of intravascular COP pi p (r = 0.936, P less than 0.001, n = 83). The average slope dQs/d pi p was 0.20 microliter min-1 cmH2O-1 (S.E. +/- 0.01 microliter min-1 cmH2O-1), the slope depending on hydraulic conductance and osmotic reflection coefficient. Trans-synovial flow was a negative linear function of synovial capillary pressure (Pc). Absolute slope dQs/d pi p was on average only 78% of dQs/dPc in the same joint. The osmotic reflection coefficient of the blood-joint barrier to serum albumin was estimated from these slopes as 0.78-0.81 (S.E.M. +/- 0.06). Vascular perfusion with a hyperosmolar solution of glucose, sucrose or NaCl generated a transient, rapidly decaying osmotic absorption from the joint cavity, with a half-life of 17-60 s. A reversed osmotic transient occurred on reperfusion with isotonic fluid. It was concluded that the blood-joint barrier, which comprises fenestrated endothelium and synovial intima, approximates to an imperfect semipermeable membrane for albumin solutions, justifying the application of Starling's hypothesis to trans-synovial flow. For small solutes the tissues form a highly permeable but nevertheless slightly osmotically reflective membrane.

Interaction of plasma colloid osmotic pressure and joint fluid pressure across the endothelium-synovium layer: significance of extravascular resistance.

Fluid exchanges between blood and a synovial joint cavity across two membranes in series--synovial capillary wall (fenestrated) and synovial intima (modified connective tissue). The relation between transsynovial absorption of intraarticular Krebs solution (flow Qs) and plasma colloid osmotic pressure pi p was investigated in rabbit knees perfused at constant blood pressure. Intraarticular pressure Pj was independently controlled. Linear relations between transsynovial flow and plasma colloid osmotic pressure established that transsynovial flow obeys the Starling hypothesis. However osmotic conductance, dQs/d pi p, increased 3.9 times when Pj was raised from 6 cm H2O or subatmospheric pressure to 18 cm H2O--the "yield phenomenon." Comparison of the effects of pi p and capillary pressure revealed no major change in the osmotic reflection coefficient of the blood-joint barrier to albumin upon raising Pj. The large increase in osmotic conductance was predicted quantitatively by a previous model (prediction 3.8 X) based on increases in extravascular (intimal) conductance as a function of extravascular pressure. It is argued that capillary endothelium is not the sole significant hydraulic resistance in this pathway. In the terminology of Intaglietta and de Plomb (1973) synovial capillaries are functionally intermediate between "tubes" and "tunnels."

Osmotic flows across the blood-joint barrier.

The effective osmotic pressure across the blood-joint barrier is a key factor controlling synovial fluid volume and joint effusions. The effect of plasma colloid osmotic pressure (COP) on trans-synovial flow was studied directly in rabbit knees expanded by intra-articular fluid infusion. The synovial microcirculation was perfused with blood of varying COP. Absorption of fluid from the joint cavity was a linear function of COP; but albumin COP was only 78% effective across the blood-joint interface. Hyperosmolar solutions of small solutes (e.g., glucose) generated transient osmotic flows across the blood-joint barrier, but far less effectively than albumin. The hydraulic permeability of synovium increased at pathological intra-articular pressures--a phenomenon of potential importance to effusion kinetics.