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David C Ford,1 Naomi V Dahl,2 William E Strauss,2 Charles F Barish,3 David J Hetzel,4 Kristine Bernard,2 Zhu Li,2 Lee F Allen,2 1Toronto Digestive Disease Associates, Inc, Vaughan Endoscopy Clinic, Vaughan, ON, Canada; 2AMAG Pharmaceuticals, Inc, Waltham, MA, 3Wake Gastroenterology, Wake Research Associates, Raleigh, NC, USA; 4Department of Gastroenterology, Royal Adelaide Hospital, Adelaide, SA, Australia Introduction: Iron deficiency anemia (IDA) is common in patients with gastrointestinal (GI) disorders and can adversely affect quality of life. Oral iron is poorly tolerated in many patients with GI disorders. Ferumoxytol is approved for the intravenous treatment of IDA in patients with chronic kidney disease. This study aimed to evaluate the efficacy and safety of ferumoxytol in patients with IDA and concomitant GI disorders. Patients and methods: This analysis included 231 patients with IDA and GI disorders from a Phase III, randomized, double-blind, placebo-controlled trial evaluating ferumoxytol (510 mg ×2) versus placebo in patients who had failed or were intolerant of oral iron therapy. The primary study end point was the proportion of patients achieving a ≥20 g/L increase in hemoglobin (Hgb) from baseline to Week 5. Other end points included mean change in Hgb, proportion of patients achieving Hgb ≥120 g/L, mean change in transferrin saturation, and patient-reported outcomes (PROs). Results: Significantly more patients with IDA receiving ferumoxytol achieved a ≥20 g/L increase in Hgb versus placebo (82.1% vs 1.7%, respectively; P

The effect of a single oral dose of omeprazole (90 mg) on gastric emptying was assessed with a dual isotope scintigraphic technique in eight patients with a history of duodenal ulcer disease. Omeprazole had no significant effect on solid or liquid gastric emptying. The bioavailability (AUC0-2 h) of omeprazole in all patients was greater than that required for total suppression of acid secretion. No adverse clinical or laboratory effects were observed. [ABSTRACT FROM AUTHOR]

We studied the effect of single 08.00 h doses of omeprazole or placebo on gastric acid secretion during the following night, 14 to 23 h after administration, in seven male subjects with duodenal ulcer. The drug was given orally, double-blind, in randomized order. Omeprazole 20 mg, 40 mg and 80 mg reduced mean total overnight acid output by 43%, 73% and 91% respectively and median pH increased from 1.4 with placebo to 1.6, 3.1 and 7.0 respectively. The inhibitory effect was maintained throughout the study period. No clinical side effects or abnormalities of laboratory screening tests were seen. Omeprazole is well tolerated and administration at 08.00 h produces prolonged dose related inhibition of acid output during the following night. [ABSTRACT FROM AUTHOR]

There are several newer intravenous iron formulations to treat iron deficiency and its anaemia. Its use in the primary care setting has been infrequent compared to tertiary centres, due to historical concerns such as anaphylaxis. There is a lack of overall comparison among the intravenous formulations of iron. Compared to oral iron therapy, the newer intravenous formulations, which allow a complete or near-complete replacement in a single sitting of 15-30 minutes, have an improved safety profile with better tolerability, efficacy and effectiveness. They are suited for administration in the primary care setting. The four non-dextran formulations (ferric carboxymaltose, iron sucrose, iron isomaltoside and ferumoxytol) share an equal or near equal efficacy and safety profile. This article also outlines how to provide iron infusion safely and effectively in the community., Competing Interests: Nil.

Background: Vedolizumab (VDZ), an α4β7 anti-integrin antibody, is efficacious in the induction and maintenance of remission in ulcerative colitis (UC) and Crohn's disease (CD). In the GEMINI long-term safety study, enrolled patients received 4-weekly VDZ. Upon completion, patients were switched to 8-weekly VDZ in Australia. The clinical success rate of treatment de-escalation for patients in remission on VDZ has not been described previously., Aim: To determine the proportion of patients who relapsed after switching from 4 to 8-weekly VDZ, the mean time to relapse, and the recapture rate when switching back to 8-weekly dosing., Materials and Methods: This was a retrospective, observational, multicenter study of patients previously recruited into GEMINI long-term safety in Australia. Data on the demographics and biochemical findings were collected., Results: There were 34 patients [23 men, mean age 49.1 (±13.1) years] and their mean disease duration was 17.6 (±8.5) years. The mean 4-weekly VDZ infusion duration was 286.5 (±48.8) weeks. A total of five (15%) patients relapsed on dose-interval increase (4/17 UC, 1/17 CD) at a median duration from dose interval lengthening to flare of 14 weeks (interquartile range=6-25). Eighty percent (4/5) of patients re-entered remission following dose-interval decrease back to 4-weekly. No clinical predictors of relapse could be determined because of the small cohort size., Conclusion: The risk of patients relapsing when switching from 4 to 8-weekly VDZ ∼15% and is similar between CD and UC. Dose-interval decrease recaptures 80% of patients who relapsed. Therapeutic drug monitoring of VDZ may be of clinical relevance.

Surgical and radiation therapy for DCIS and early stage 1 and 2 invasive breast cancer is detailed and described.

Background & Aims: The burden of ulcerative colitis (UC) in relation to disease severity is not well documented. This study quantitatively evaluated the relationship between disease activity and quality of life (QoL), as well as health care utilization, cost, and work-related impairment associated with UC in an Australian population., Methods: A cross-sectional, noninterventional, observational study was performed in patients with a wide range of disease severity recruited during routine specialist consultations. Evaluations included the Assessment of Quality of Life-8-dimension (AQoL-8D), EuroQol 5-dimension, 5-level (EQ-5D-5L), the disease-specific Inflammatory Bowel Disease Questionnaire (IBDQ), and the Work Productivity and Activity Impairment (WPAI) instrument. The 3-item Partial Mayo Score was used to assess disease severity. Health care resource utilization was assessed by chart review and patient questionnaires., Results: In 175 patients, mean (SD) AQoL-8D and EQ-5D-5L scores were greater for patients in remission (0.80 [0.19] and 0.81 [0.18], respectively) than for patients with active disease (0.70 [0.20] and 0.72 [0.19], respectively, both Ps<0.001). IBDQ correlated with both AQoL-8D (r=0.73; P<0.0001) and EQ-5D-5L (0.69; P<0.0001). Mean 3-month UC-related health care cost per patient was AUD $2914 (SD=$3447 [mean for patients in remission=$1970; mild disease=$3736; moderate/severe disease=$4162]). Patients in remission had the least work and activity impairment., Conclusions: More severe UC disease was associated with poorer QoL. Substantial health care utilization, costs, and work productivity impairments were found in this sample of patients with UC. Moreover, greater disease activity was associated with greater health care costs and impairment in work productivity and daily activities., (Copyright © 2013 European Crohn's and Colitis Organisation. Published by Elsevier B.V. All rights reserved.)

Background: Acute severe colitis (ASC) is a serious condition with possible outcomes of emergency colectomy and mortality. Validated guidelines exist to help avoid these., Aims: To examine local adherence to guidelines and identify (a) opportunities to improve care and (b) possible barriers to adherence., Methods: Retrospective, hospital-wide audit of all patients with ASC during a 2-year period (2009-2010) at a major metropolitan hospital. Cases were identified by an electronic search of all discharges with International Classification of Diseases-10 codes for colitis, colectomy, ulcerative colitis or Crohn disease., Results: Twenty-six patients had 30 ASC admissions (14 female). Most admissions were under gastroenterology (25), 4 (13%) were under general medicine and 1 was under general surgery. Only 8 patients' (26%) management (all under gastroenterology) included all major details: blood investigations, Clostridium difficile test, abdominal X-ray, colonic examination and venous thromboembolism prophylaxis. Only one patient had formal severity scoring on admission, and seven patients (24%) had descriptive severity recorded. On day 3, nine patients (30%) had some recorded severity assessment; however, no formal criteria were used. Four had colectomy, three during first admission and one on re-admission. Of these patients, three received cyclosporine prior to colectomy. The mean duration of admission was 10 days (standard deviation 10.54, range 1-61)., Conclusion: Opportunities to optimise care exist including formal severity assessments on days 1 and 3, better deep vein thrombosis/pulmonary embolism prophylaxis and prompt colonic examination. Admission under teams other than gastroenterology appeared to be a barrier to better care. Despite the low rate of ideal management, the colectomy rate was acceptably low at 20%., (© 2012 The Authors; Internal Medicine Journal © 2012 Royal Australasian College of Physicians.)

Background: Recently, promulgated inflammatory bowel disease (IBD) guidelines seek to decrease the need for surgery by improving disease control. However, resection rates remain static., Aims: We therefore sought to determine the proportion of patients coming to surgery where preoperative management was not optimal according to guidelines., Methods: Case notes of all patients with resection surgery for IBD from January 2007 to March 2008 at a metropolitan teaching hospital were retrospectively reviewed. Judgement was made as to whether preoperative management was optimal or suboptimal depending on whether it met guidelines., Results: A total of 22 subjects with IBD-related resections were identified (15 males and seven females). In total, 17 had Crohn's disease (CD) (11 males) and five ulcerative colitis (UC) (four males). There were 10 smokers (nine CD and one UC). The two most common indications for surgery were inflammatory mass/abscess (n= 8) and refractory to medical therapy (n= 7). While all patients with known IBD (20/22) had seen a gastroenterologist in the past, five known IBD patients had resections undertaken without preoperative gastroenterologist input. Overall preoperative management was judged as optimal in only (9/22) 41%. Of those whose therapy did not meet guidelines (n= 13), five had azathioprine at doses <2 mg/kg, one declined therapy and nine with CD were current smokers., Conclusions: Over 50% of IBD resection patients had suboptimal preoperative management, with sub-therapeutic thiopurine dosing and smoking in CD the main problems. Thus, there are significant gains to be made with better use of standard therapies, as it appears that ∼50% of resection surgery was 'potentially avoidable'., (© 2010 The Authors. Internal Medicine Journal © 2010 Royal Australasian College of Physicians.)

Background and Aim: A significant proportion with inflammatory bowel disease (IBD) exhibit an adverse clinical phenotype reflected in endpoints like surgery and hospitalizations. We sought to identify clinico-demographic factors associated with these adverse consequences that may be amenable to change., Methods: Over 6 months IBD patients visiting a metropolitan center were prospectively identified and given a comprehensive survey addressing patient knowledge, mental health and satisfaction with medical care along with other clinical data. Logistic regression analyses assessed for associations between clinico-demographic variables and adverse clinical endpoints (previous surgery [ever] and/or recent inpatient admission over a 16 month observation period)., Results: Of 256 IBD patients, 162 responded (response rate 63%); 95 (59%) had Crohn's disease (CD), 63 (40%) ulcerative colitis (UC), four indeterminate colitis; 53% were female. Factors associated with a greater likelihood of hospitalization included moderate/severe disease activity, psychological co-morbidity, numbers of medications and outpatient visits (odds ratio [OR] 7.09 [2.83-17.76], 4.13 [1.25-13.61], 1.26 [1.03-1.54], 1.17 [1.00-1.37] respectively; all P < 0.05). Post-surgical patients were more likely to have CD, more currently active disease and longer disease duration (OR 8.55 [2.43-29.4], 3.52 [1.26, 9.87], 1.14 [1.08, 1.21] respectively; all P < 0.02), yet were less likely to have previously seen a gastroenterologist, OR 0.25 [0.08-0.76] (P = 0.01)., Conclusions: 'At risk' patients (those previously operated, with ongoing disease activity, dissatisfaction and/or psychological comorbidities) may benefit from early identification and more intensive management. Specialist gastroenterology care appears to be under-utilized in operated patients yet may reduce future IBD morbidity.

Background & Aims: Understanding patients' expectations at initial consultation for functional gastrointestinal disorders (FGIDs) might influence future health care utilization. Ideally, patients and doctors would have a common understanding of the issues involved. We sought to investigate this with matched questionnaires., Methods: Patients' needs/expectations/understanding were compared with gastroenterologists' and general practitioners' awareness of these. Patients were followed up to investigate satisfaction with and outcomes of specialist consultation., Results: Specialists underestimated the number and severity of patients' symptoms (in 43% and 41%, respectively), and patients and specialists had quite discordant views on what treatment would best suit their symptoms. Strikingly, only 1 of 13 patients available for follow-up agreed with or accepted the functional diagnosis, despite all being diagnosed by a specialist as having an FGID., Conclusions: In FGIDs there is a communication gap between patients and gastroenterologists. Importantly, at follow-up, patients do not acknowledge their FGID diagnosis. This communication gap and lack of acceptance of a functional diagnosis are likely to influence future management and health care utilization.

Background: In independent studies, IBD, IBS and HCV have each been associated with a substantially increased risk of psychological problems such as depression and anxiety and impairment of quality of life compared to the general healthy population. However, the relative psychological burden for each of these diagnoses is unknown as it has never been compared contemporaneously at one institution. Current local data are therefore needed to enable an evidence-based allocation of limited clinical psychological resources., Methods: Overall, 139 outpatients (64 IBD, 41 HCV, and 34 IBS) were enrolled in this cross-sectional study. The HADS, SCL90, SF-12 and appropriate disease-specific activity measures were administered. Differences between groups were assesed with ANOVA, the Chi-Square test and the independent samples t-test (two-tailed)., Results: Each of the three groups had significantly lower quality of life than the general population (p < 0.05). Overall, a total of 58 (42%) participants met HADS screening criteria for anxiety and 26 (19%) participants for depression. The HCV group had a significantly higher prevalence of depression than either of the other groups (HCV = 34%, IBS = 15% and IBD = 11%, p = 0.009). In the SCL90, the three disease groups differed on 7 out of 12 subscales. On each of these subscales, the HCV group were most severely affected and differed most from the general population., Conclusion: Patients with these common chronic gastrointestinal diseases have significant impairment of quality of life. Anxiety is a greater problem than depression, although patients with HCV in particular, should be regularly monitored and treated for co-morbid depression. Evaluation of specific psychological interventions targeting anxiety is warranted.

Meat tenderness has been difficult to improve using standard genetic selection. Marker assisted selection holds great promise if markers for meat tenderness can be identified. Here, we report quantitative trait loci (QTL) for beef tenderness identified in 598 animals of three Charolais-Brahman x Belmont Red pedigrees after screening the whole genome using 183 DNA markers. In addition to the usual Warner-Bratzler peak force measurements, tenderness was also measured using compression, adhesion and pressure-heat-treated peak force. Three QTL for meat tenderness in the M. longissimus lumborum muscle were found, two of which have not been reported before. One is located in the HEL9-CSSM47 interval on bovine chromosome 8 with a LOD of 3.1 and an effect of 1.02 phenotypic standard deviations for tensile strength of cooked muscle as measured by adhesion. A second QTL is located near CSRM60 on bovine chromosome 10 with a LOD of 2.4 and an effect of 0.48 phenotypic standard deviations for compression. The third QTL is in a region of bovine chromosome 7 that has previously been reported to have a QTL affecting peak force. This region also shows effects on compression and a combined tenderness index. These QTL are all for the myofibrillar component of meat tenderness. No QTL were found for pressure-treated peak force, which is an estimate of the connective tissue component muscle of meat tenderness.

A meta-analysis was undertaken reporting on the association between a polymorphism in the Thyroglobulin gene (TG5) and marbling in beef cattle. A Bayesian hierarchical model was adopted, with alternative representations assessed through sensitivity analysis. Based on the overall posterior means and posterior probabilities, there is substantial support for an additive association between the TG5 marker and marbling. The marker effect was also assessed across various breed groups, with each group displaying a high probability of positive association between the T allele and marbling. The WinBUGS program code used to simulate the model is included as an Appendix available online at www.edpsciences.org/gse.

Swamp and river buffalo mitochondrial DNA (mtDNA) was sequenced for 303 bp of the cytochrome b gene for 54 animals from 14 populations, and for 158 bp of the D-loop region for 80 animals from 11 populations. Only one cytochrome b haplotype was found in river buffalo. Of the four haplotypes identified in swamp buffalo, one found in all populations is apparently ancestral both to the other swamp haplotypes and to the river haplotype. The phylogenetic relationships among the 33 D-loop haplotypes, with a cluster of 11 found in swamp buffalo only, also support the evolution of domesticated swamp and river buffalo from an ancestral swamp-like animal, most likely represented today by the wild Asian buffalo (Bubalus arnee). The time of divergence of the swamp and river types, estimated from the D-loop data, is 28,000 to 87,000 years ago. We hypothesise that the species originated in mainland south-east Asia, and that it spread north to China and west to the Indian subcontinent, where the rive type evolved and was domesticated. Following domestication in China, the domesticated swamp buffalo spread through two separate routes, through Taiwan and the Philippines to the eastern islands of Borneo and Sulawesi, and south through mainland south-east Asia and then to the western islands of Indonesia.

In this study, four new markers located on bovine Chromosome 1 were tested for linkage with the polled condition in the Simmental and Pinzgauer breeds. The microsatellites INRA212 (D1S42) and the gene for keratin-associated protein 8 (KAP8) show significant linkage with polled at theta = 0.00 (Lod = 6.92), and theta = 0.033 (Lod = 6. 52) respectively. The microsatellite INRA117 (D1S20) and the gene for interferon-alpha receptor (IFNAR) show maximum Lod scores of 2.1 and 1.8 at a recombination rate of zero.

The genetic basis of the high resistance of Indonesian Thin Tail (ITT) sheep against Fasciola gigantica has been studied by measuring the resistance levels of ITT sheep, St. Croix sheep and their F2 and F3 crossbreds. All of the sheep were bred and reared in the same environment. Approximately half of the F2 and F3 crossbreds were as resistant as the ITT parental breed, one-quarter had the low resistance of the St. Croix parental breed and the rest had an intermediate level of resistance. It is concluded that the high resistance is determined by a major gene with incomplete dominance. The prevalence of the gene in the ITT sheep population is estimated to be about 90%. The resistance may be innate or acquired; but, regardless of the mechanism, it could be used to control fasciolosis caused by F. gigantica by breed substitution or by crossbreeding with other breeds of sheep.

Cutaneous metastases of gestational trophoblastic disease are extremely uncommon. A patient with metastatic, poor prognosis disease and a large metastatic lesion on her left fifth digit is presented. The clinical course and complete response to EMACO chemotherapy are outlined. The presence of metastatic disease in a reproductive-age woman requires consideration of gestational trophoblastic disease in the differential diagnosis.

DNA microsatellites have found widespread application in gene mapping, pedigree determination and population genetics. In closely related species such as bovids, heterologous polymerase chain reaction (PCR) primers may in some cases be used, bypassing the need to isolate and characterize microsatellite-containing sequences and design PCR primers. We report on the ability of a set of eighty bovine derived DNA microsatellite primers to amplify sequences in the two types (swamp and river) of water buffalo (Bubalus bubalis). Number of alleles and per cent heterozygosities in a large number of animals were determined on a subset of microsatellite loci selected on the robustness of the primers. These loci will form the basis of a set of polymorphic DNA markers for use in water buffalo.

The cosmid-derived microsatellite CSSM 25 has previously been shown to map to bovine syntenic group U2 by linkage and hybrid somatic cell analysis. We have mapped the cosmid by fluorescent in situ hybridization to bovine Chromosome (Chr) 9q17-21 and ovine Chr 8q17-21 and hence assign U2 to Chr 9 in cattle. Bovine Chr 9 and ovine Chr 8 show strong banding pattern homology, and the localization of CSSM 25 to the same region confirms the strong conservation of gene locations on these chromosomes.

A case-control study was undertaken to investigate the effects of smoking, alcohol consumption, use of non-steroidal anti-inflammatory and other analgesic medications and family and medical history on the risk of ulcerative reflux oesophagitis (URO). We recruited 191 cases with URO diagnosed at endoscopy, 162 hospital controls who had also undergone endoscopy and 140 community controls from the Adelaide metropolitan area. From these three groups of subjects, 134 case-community control pairs, Matched on age, sex and postcode of residence and 142 case-hospital control pairs, matched on age, sex, hospital and endoscopist, were formed. Elevated non-significant risks were found in those smoking at least 20 cigarettes per day relative to those who never smoked (relative risk = 1.9, 95% confidence interval: 0.9-3.9 in case-hospital control pairs; relative risk = 1.9, 95% confidence interval: 0.9-3.7 in case-community control pairs). There was no elevation in risk associated with the use of non-steroidal anti-inflammatory drugs, with alcohol consumption, factors related to medical and reproductive history, nor with family history except for paternal history of heartburn (relative risk = 2.5, 95% confidence interval: 1.2-5.4 in case-hospital control pairs; relative risk = 1.9, 95% confidence interval: 1.0-4.0 in case-community control pairs). With the possible exception of smoking, no other risk factors for ulcerative reflux oesophagitis related to lifestyle are apparent.

The aim of this study was to compare recurrence rates of reflux oesophagitis (after endoscopic healing with omeprazole) over a 12 month period of randomised, double blind, maintenance treatment with either daily omeprazole (20 mg every morning; n = 53), weekend omeprazole (20 mg on three consecutive days a week, n = 55) or daily ranitidine (150 mg twice daily, n = 51). Patients were assessed for relapse by endoscopy (with gastric biopsy) at six and 12 months, or in the event of symptomatic recurrence, and serum gastrin was monitored. At 12 months, the estimated proportions of patients in remission (actuarial life table method) were 89% when receiving daily omeprazole compared with 32% when receiving weekend omeprazole (difference 57%, p < 0.001, 95% confidence intervals: 42% to 71%) and 25% when receiving daily ranitidine (difference 64%, p < 0.001, 95% confidence intervals: 50% to 78%). Median gastrin concentrations increased slightly during the healing phase, but remained within the normal range and did not change during maintenance treatment. No significant pathological findings were noted, and no adverse events were attributable to the study treatments. In conclusion, for patients who respond favourably to acute treatment with omeprazole 20 mg every morning, the drug is a safe and highly effective maintenance treatment for preventing relapse of reflux oesophagitis and its associated symptoms over 12 months. By contrast, weekend omeprazole and daily ranitidine were ineffective.

Microsatellites or simple sequence repeat (SSR) polymorphisms are used widely in the construction of linkage maps in many species. High levels of polymorphism coupled with the ease of analysis of the polymerase chain reaction (PCR) have resulted in this type of maker being one of the most widely used for genetic analysis. In this paper we describe 58 polymorphic bovine microsatellites that were isolated from insert size selected bovine genomic libraries. Primer sequences, number of alleles, and heterozygosity levels in cattle reference families are reported. Chromosomal locations for 47 of these microsatellites as well as for 7 previously described systems derived from entries in the Genbank or EMBL databases have been determined. The markers map to 24 syntenic or chromosomal locations. Polymorphic bovine microsatellites were estimated to occur, on average, every 320 kb, and there is no evidence of clustering in the genome. Thirty of the bovine-derived microsatellite systems gave specific and polymorphic products in sheep, adding to the number of useful markers in that species.

A minisatellite sequence (RD1613) was isolated from a bovine cosmid genomic library and its chromosomal location determined in cattle and sheep. In cattle, somatic cell hybrid panel analysis assigned RD1613 to the syntenic group U10 with a concordancy of 100%. In situ hybridization placed RD1613 onto bovine chromosome 1 in the region of bands q36-qter. This is the first in situ localization to chromosome 1 in cattle and allows the provisional assignment of syntenic group U10 to this chromosome. It was also found that RD1613 hybridized strongly to sheep genomic DNA. In situ hybridization localized RD1613 to sheep chromosome 1q36-qter, which is consistent with homology between cattle chromosome 1 and sheep chromosome 1q. The RD1613 probe detects a polymorphic single locus marker (designated D1S1) in both cattle and sheep and will be very useful in linkage studies.

Animals from the Booroola line of Australian Merino sheep are characterized by a high ovulation rate that can be attributed to the presence of a codominant allele (FecB). The specific function of the gene has not been identified. Effective use of the trait within the sheep breeding industry requires one or more genetic markers that can distinguish between alternative alleles at the locus Fec. With a combination of DNA minisatellite markers and polymorphic protein markers, a cluster of seven minisatellite fragments has been identified as being linked to the Fec gene and to the ovine A blood group locus. The minisatellite fragments have been derived from multilocus probes and hence cannot be used to define the chromosomal location of the Fec gene or to serve as diagnostic markers for Fec. The derivation of cloned single locus markers from the minisatellite fragments will enable finer scale mapping of the Fec and the A blood group locus in sheep.

To identify physical and genetic anchor loci on bovine chromosomes, 13 cosmids, obtained after the screening of partial bovine cosmid libraries with the (CA)n microsatellite motif, were mapped by fluorescence in situ hybridization (FISH). Eleven cosmid probes yielded a specific signal on one of the bovine chromosomes and identified the following loci: D5S2, D5S3, D6S3, D8S1, D11S5, D13S1, D16S5, D17S2, D19S2, D19S3, D21S8. Two cosmids produced centromeric signals on many chromosomes. The microsatellite-containing regions were subcloned and sequenced. The sequence information revealed that the two centromeric cosmids were derived from bovine satellites 1.723 and 1.709, respectively. A cosmid located in the subtelomeric region of Chromosome (Chr) 17 (D17S2) had features of a chromosome-specific satellite. Primers were designed for eight of the nonsatellite cosmids, and seven of these microsatellites were polymorphic with between three and eight alleles on a set of outbred reference families. The polymorphic and chromosomally mapped loci can now be used to physically anchor other bovine polymorphic markers by linkage analysis. The microsatellite primers were also applied to DNA samples of a previously characterized panel of somatic hybrid cell lines, allowing the assignment of seven microsatellite loci to defined syntenic groups. These assignments confirmed earlier mapping results, revealed a probable case of false synteny, and placed two formerly unassigned syntenic groups on specific chromosomes.

Glycogenosis type II is an inherited lysosomal storage disorder caused by acid alpha-glucosidase deficiency. The disorder is inbred in Brahman cattle, and the incidence of carriers in Australian herds averages 15%. Affected animals are lethargic and die typically in the eighth or ninth month after birth. A complete lack of acid alpha-glucosidase synthesis was demonstrated in cultured fibroblasts and muscle tissue of affected animals. Moreover, the tissue was found to be devoid of acid alpha-glucosidase mRNA. Gross abnormalities of the acid alpha-glucosidase gene itself were not detected by Southern blot analysis. These results suggest Brahman glycogenosis type II to be caused by a point mutation or a micro deletion/insertion in the acid alpha-glucosidase gene.

The gamma fibrinogen gene (FGG) was localised in both cattle and sheep using in situ hybridisation. The probe employed was a 1-kb bovine cDNA fragment. Based on observations of QFQ-banded chromosome preparations, this locus is on bovine chromosome 17q12-->q13 and on the homologous sheep chromosome 17. This localisation is, to our knowledge, the first assignment to chromosome 17 in either the bovine or ovine genome. In addition to localising FGG to this chromosome, the assignment provisionally maps the previously unassigned syntenic group U23, containing (besides FGG) the genes for mitochondrial aldehyde dehydrogenase 2 (ALDH2), interleukin 2 (IL2), immunoglobulin lambda (IGL), and beta fibrinogen (FGB), to chromosome 17 in cattle and probably to the same chromosome in sheep.

The HER-2/neu oncogene encodes for a specific cell-surface glycoprotein similar to the human growth factor receptor. An analysis of 247 patients with endometrial cancer treated between 1979 and 1983 was performed using an immunoperoxidase technique on paraffin-embedded tissue samples to detect HER-2/neu overexpression. Specimens were graded blindly with regard to HER-2/neu staining intensity. Overexpression of HER-2/neu was identified as strong in 37 patients (15%), mild in 144 (58%), and none in 66 (27%). The 5-year progression-free survival was 56% for the strong, 83% for the mild, and 95% for the nonstaining groups. The strong (P < 0.0001) and the mild (P = 0.028) staining groups were distinct from the nonstaining group in predicting progression-free survival. Likewise, strong overexpression was associated with a poor (51%) overall survival (P < 0.0001). Multivariate analysis revealed that intense overexpression had independent significance in predicting progression-free (P = 0.0003) and overall survival (P < 0.0001). In stage I patients (203), the 5-year progression-free survival was 62% for the strong and 97% for the nonstaining groups (P = 0.0007). This retained independent significance when subjected to multivariate analysis (P = 0.0017). Other significant stage I prognostic factors in multivariate analysis included DNA ploidy, histologic subtype, and histologic grade but not depth of invasion.

Reflux oesophagitis is a chronic relapsing disorder. When treatment is stopped after successful short-term healing of oesophagitis, high relapse rates (80% within 6 months) indicate that prolonged treatment is necessary in order to maintain remission. The results of three long-term, multicentre, controlled, double-blind clinical trials comparing different regimens of omeprazole with ranitidine are reviewed. Omeprazole, 20 mg daily, was found to be a highly effective maintenance therapy in patients with ulcerative oesophagitis, keeping 67-89% of patients in remission for 1 year, compared with 10-25% of patients treated with ranitidine, 150 mg twice daily. Weekend omeprazole therapy, 20 mg daily every Friday, Saturday and Sunday, was, as with daily ranitidine, relatively ineffective. All treatment regimens were well tolerated and gastric mucosal biopsies showed no qualitative changes in gastric enterochromaffin-like cells.

Bovine and ovine microsatellite sequences were extracted from the EMBL and GENBANK databases. When analysed for number of alleles and degree of heterozygosity in the CSIRO cattle reference families, allele numbers range from 1 to 14 with heterozygosities, in the polymorphic systems ranging from 15.8% to 100%. Six (46%) of the 13 bovine systems tested gave specific and polymorphic products in sheep. Similarly 2 of the 4 ovine systems gave specific and polymorphic products in cattle. These data define 11 bovine and 8 ovine microsatellite systems which are associated with known genes and are thus useful for comparative mapping studies.

A prospective assessment was made of the outcome 4 years after diagnosis of recurrence in a group of 27 patients with documented ulceration after highly selective vagotomy (16 symptomatic recurrence and 11 asymptomatic). In the 16 patients with a previous symptomatic recurrence, eight of the 11 patients with duodenal ulcer underwent a further endoscopy at 4 years and one active ulcer was found. Five patients with previous symptomatic gastric ulcer recurrence have all undergone further surgery. In the 11 patients who originally had an asymptomatic ulcer recurrence (five gastric, six duodenal) no patient has undergone further surgery, although two patients with a recurrent gastric ulcer and two with a recurrent duodenal ulcer subsequently developed symptoms from their ulcer and required H2 receptor blocker therapy. Eight of the 11 originally asymptomatic patients underwent further endoscopy at 4 years and two further duodenal ulcers were found. After highly selective vagotomy, asymptomatic ulcer recurrence occurs frequently and 40 per cent of these patients may develop symptoms.

The high degree of polymorphism displayed by DNA microsatellites makes them useful as DNA markers in linkage studies. A search of the DNA sequence databases revealed that the locations of dinucleotide microsatellites are often conserved among mammalian species, enabling the prediction of the presence of DNA microsatellites using comparative genetic data. In closely related species such as cattle and sheep, this conservation was close enough to allow PCR primers designed for use in one species to be used to analyze microsatellite length polymorphism in the other. A total of 48 sets of primer pairs, flanking bovine microsatellites and giving polymorphic PCR products in that species, were tested with template DNA from sheep, horses, and humans. Specific products were obtained in 27 cases (56%) with ovine DNA, 20 of which (42%) showed polymorphisms. With equine DNA, 3 (6.2%) gave specific but monomorphic products, while no specific products were obtained using human DNA. The ability to use heterologous PCR primers, coupled with comparative mapping information will facilitate the use of DNA microsatellites in gene mapping studies in closely related species such as cattle and sheep, rat and mouse, or primates.

Uterine incarceration that manifests during the third trimester or at term is a serious and rare complication of pregnancy. The pregnant patient may complain of low-abdominal pain, low-back pain, urinary retention, and constipation, or the patient may be asymptomatic until labor begins. The diagnosis is difficult, and physical findings can be misleading. Ultrasonography and magnetic resonance imaging can be helpful if the anteriorly displaced cervix is clearly depicted. If incarceration of the retroverted uterus persists until term, a cesarean section is necessary. Recurrent uterine incarceration has been reported; therefore, the patient should be monitored closely during subsequent pregnancies. Herein we describe three cases of uterine incarceration during the third trimester and review the literature with respect to incidence, differential diagnosis, management, and complications of this condition.

The locus for the beta-subunit of the follicle stimulating hormone gene (FSHB) has been determined in both cattle and sheep by in situ hybridization of a bovine and an ovine cDNA probe, respectively, to metaphase chromosomes. Our results show that the FSHB locus is on cattle chromosome 15 in the region of bands q24-qter and in sheep on the cytogenetically homologous chromosome 15, also in the region q24-qter. The mapping of the FSHB gene in cattle together with the location of other genes (CAT, HBB and PTH) previously found to be syntenic in cattle and on human chromosome 11p, defines an evolutionarily conserved synteny. The localization of the FSHB gene to a cytogenetically homologous region in cattle and sheep is consistent with the hypothesis of extensively conserved chromosome structure in these two species.

Between 1982 and 1989, 19 patients with gynecologic carcinoma, paraneoplastic cerebellar degeneration, and seropositivity for anti-Purkinje cell cytoplasmic antibodies were identified at our institution. Seven of the patients had no clinical, computed tomographic, or magnetic resonance imaging evidence of cancer but had undergone laparotomy solely because anti-Purkinje cell antibodies were found in their serum; all had high-grade adenocarcinoma. Cerebellar symptoms preceded or coincided with the initial cancer diagnosis in 15 patients and preceded the diagnosis of recurrent cancer in 4 patients. The cancers were 14 ovarian, 2 fallopian tube, 2 surface papillary, and 1 poorly differentiated metastatic adenocarcinoma in a periaortic lymph node. Two remarkable surgical observations in patients with high-grade ovarian and tubal cancers were the conspicuous lack of peritoneal implants and the small metastatic volume. A comparison of the 8 patients who had primary stage III cancer with 24 matched control patients without paraneoplastic cerebellar degeneration revealed no difference in primary tumor volume but a significantly smaller volume of metastatic tumor in the seropositive group (P = 0.05). Anti-Purkinje cell antibodies were not detected in 111 neurologically normal patients with advanced ovarian cancer. The small metastatic volume in the face of high-grade and advanced stage malignancy in seropositive patients with paraneoplastic cerebellar degeneration suggests that an immune response to the tumor (presumably cross-reactive with cerebellar cells) may impair the metastatic process. Earlier diagnosis and treatment of cancer, based on prompt serologic testing, may offer an improved neurologic and oncologic prognosis.

Single-sire natural mating data from a beef cattle herd in tropical Australia were used to estimate heritabilities of cow fertility (hc2), heritabilities of bull fertility (hb2) and genetic correlations between cow and bull fertility (rg) within each of six genotypes. Estimates of hc2 and hb2 were low, averaging .11 and .08, respectively. The pooled estimate of rg was 0.16, indicating that cow and bull fertility are favorably genetically correlated and therefore that cow fertility could be genetically improved by indirect selection on bull fertility, or some more heritable component of bull fertility.

Natural infestations of the cattle tick Boophilus microplus, levels of the buffalo fly Haematobia irritants exigua and faecal nematode egg concentrations (Bunostomum phlebotomum, Cooperia spp., Haemonchus placei, Oesophagostomum radiatum and Trichostrongylus axei) were assessed in 221 Belmont Red calves during the post-weaning period, when the animals were between 9 and 18 months of age. In addition, the 98 males of this group were challenged with B. microplus larvae on two separate occasions. There were strong positive correlations among replicate assessments of the same parasite. Field tick counts and tick counts following deliberate challenge were strongly correlated, and both showed negative correlations with post-weaning weight gain. There was a weak positive correlation between buffalo fly counts and post-weaning weight gain. There was a negative correlation between total worm egg count and weight gain. Among worm species, only the effect of O. radiatum on weight gain was significant. Cattle with bovine major histocompatibility (BoLA) antigens W6.1 and W7 had significantly fewer ticks than cattle lacking these antigens. Cattle with BoLA antigens W7 and CA36 had lower concentrations of nematode eggs in their faeces than cattle lacking these BoLA antigens.

Three methods of semen collection from Alabio drakes were compared: the use of an artificial vagina (AV), electro ejaculation (EE) and manual massage (MM). For the latter two methods, drakes were housed in individual cages or in groups in floor pens, while for the AV method all drakes were kept in individual cages. Training success rates of drakes for the three collection methods were similar. Drakes housed in cages produced significantly more semen with a higher sperm concentration, which maintained fertility longer than semen from floor-penned drakes. The average semen volume per ejaculate, sperm concentration and total number of sperm per ejaculate were highest for the AV method while the other two methods did not differ. The average duration of fertility was significantly longer for the AV method (8.8 d) than the EE (6.5 d) or MM methods (5.1 d). The proportion of fertile eggs for 7 d following the insemination of 2 X 10(8) spermatozoa was also highest for the AV method. Although greater skill was required from the operator, the AV method is recommended for general use because of its significantly higher semen yield and longer duration of fertility.