Post-operative volumes following endoscopic surgery for non-functioning pituitary macroadenomas are predictive of further intervention, but not endocrine outcomes.

BACKGROUND: Transsphenoidal surgery (TSS) remains the treatment of choice for non-functioning pituitary macroadenomas (NFPMA). The value of measuring tumour volumes before and after surgery, and its influence on endocrine outcomes and further treatment of the residual or recurrent tumour are unknown. METHODS: Data from patients who underwent endoscopic TSS for a NFPMA (2009-2018) in a UK tertiary centre were analysed for pre- and post-operative endocrine and surgical outcomes. RESULTS: Of 173 patients with NFPMA, 159 (61% male) were treatment naïve. At presentation, 76.2% (77/101) had ≥1 pituitary axis deficit. Older age (p = 0.002) was an independent predictor for multiple hormonal deficiencies. Preoperative tumour volume did not correlate with degree of hypopituitarism. Postoperative tumour volume and extent of tumour resection were not predictive of new onset hypopituitarism. Hormonal recovery was observed in 16 patients (20.8%) with impaired pituitary function, with the greatest recovery in the hypothalamic-pituitary-adrenal axis (21.2%, 7/33). A larger residual tumour volume was predictive of adjuvant radiotherapy (3.40 vs. 1.24 cm3, p = 0.005) and likelihood for repeat surgery (5.40 vs. 1.67cm3, p = 0.004). CONCLUSION: Pre- and post-operative NFPMA volumes fail to predict the number of pituitary hormone deficits, however, greater post-operative residual volumes increase the likelihood of further intervention to control tumour growth.

Can We Discharge Dynamically Risk-Stratified Low-Risk (Excellent Response to Treatment) Thyroid Cancer Patients After 5 Years of Follow-Up?

AIMS: The 2014 British Thyroid Association thyroid cancer guidelines recommend lifelong follow-up of thyroid cancer patients. This is probably unnecessary, can cause patient anxiety, is time consuming and places significant demand on National Health Service resources. It has been suggested that low-risk differentiated thyroid cancer (DTC) patients could be discharged to primary care once they are 5 years from diagnosis and treatment. The aim of this study was to investigate the potential safety of this practice. MATERIALS AND METHODS: In total, 756 patients with dynamically risk-stratified (DRS) low-risk/excellent response to treatment DTC treated over 2001-2013 in the Leeds region were followed after diagnostic surgery and the recurrence rate calculated. RESULTS: The median follow-up time was nearly 10 years (5-17 years). Radiological recurrence occurred in 13/756 (1.7%) patients and was always preceded by raised thyroglobulin/ thyroglobulin antibody levels. In all 13 patients elevation of thyroglobulin occurred within 5 years of diagnosis. Two additional patients were found to have rising thyroglobulin at almost 9 and 10.5 years from diagnosis, although to date radiological recurrence has not been detected. Assuming these two patients developed recurrence with longer duration of follow-up, then 0.26% (2/756) of patients would not have their recurrence discovered within 5 years of diagnosis. To detect 100% of patients with a putative recurrence in our cohort would require 10.5 years of follow-up. Four patients had transiently raised thyroglobulin, which became undetectable within 2 years (in three patients), without any treatment and radiological recurrence was not discovered. CONCLUSION: Discharge of DRS low-risk DTC patients to primary care after 5 years of secondary care follow-up is reasonable, accepting that late recurrence may occur in a very small minority of individuals (0.26%, ∼1:400). A more cautious approach would be to continue monitoring for 10 years, although the frequency of assessments could be reduced with increasing duration of follow-up.

Endemic goitre and hypothyroidism in an adult female patient dependent on total parenteral nutrition.

We present the case of a thirty-year-old female patient who was referred to the endocrinology team with an enlarging goitre and biochemical hypothyroidism. She had been dependent on total parenteral nutrition for the previous six years as a result of intestinal failure thought to be caused by possible underlying mitochondrial disease. The patient also suffers from a Desmin myopathy, and at present, the exact aetiology behind her intestinal failure is not certain. The goitre was smooth and had been enlarging slowly over the previous few months. Thyroid peroxidase antibodies were found to be within normal range. Further analysis of the case showed that twelve months earlier the patients total parenteral nutrition (TPN) feed had been altered as a result of manganese toxicity. The current feeding regimen did not contain a trace element additive which had previously supplied iodine supplementation. A little detective work established that iodine content to the TPN had been reduced, the trace element additive (Additrace) was recommenced providing 1 µmol of iodine per day, equating to 130 µg of iodine. Following this change, thyroid-stimulating hormone levels returned to normal and the goitre quickly reduced in size. We present a rare case of endemic goitre and hypothyroidism in a patient receiving inadequate iodine supplementation through total parenteral nutrition. LEARNING POINTS: Endemic goitre and hypothyroidism secondary to iodine deficiency are rare in the developed world. However, the diagnosis should be considered in the setting of a diffuse goitre and negative thyroid antibodies.Although rare, endemic goitre should be considered in patients who present with hypothyroidism and who are dependent on total parenteral nutrition.Treatment with levothyroxine is not required in endemic goitre as thyroid function tests generally normalise with the addition of iodine to the diet/total parenteral nutrition regimen.Iodine supplementation at a level recommended by the European Society for Clinical Nutrition and Metabolism (ESPEN) was observed to quickly normalise this patient's thyroid function tests.

Bovine digital dermatitis: Current concepts from laboratory to farm.

Bovine digital dermatitis (DD) is a severe infectious disease causing lameness in dairy cattle worldwide and is an important ruminant welfare problem that has considerable economic issues. Bovine DD is endemic in many regions worldwide and it is important to understand this major disease so that effective control strategies can be identified. There is substantial evidence that specific treponeme phylotypes play an important causative role in bovine DD. This review considers current research, including DD Treponema spp. investigations, associated DD pathobiology, and current and potential treatment and control options. Epidemiological data, alongside new microbiological data, help delineate important transmission routes and reservoirs of infection that allow effective interventions to be identified. Better on-farm housing hygiene, pasture access, routine footbathing and claw trimming with disinfected equipment need to be implemented to significantly reduce the incidence of DD. There is a paucity of peer reviewed research into both commonly used and novel treatments. In vitro antimicrobial susceptibility studies of DD treponemes and effective treatment of human treponematoses clearly indicate that antibiotics frequently selected for DD treatments are not the most efficacious. Whilst there are understandable concerns over milk withdrawal times in dairy cattle, more needs to be done to identify, license and implement more appropriate antibiotic treatments, since continued overuse of less efficacious antibiotics, applied incorrectly, will lead to increased disease recurrence and transmission. More research is needed into methods of preventing DD that circumvent the use of antibiotics, including vaccination and transmission blocking studies, to reduce or hopefully eradicate DD in the future.

High-level association of bovine digital dermatitis Treponema spp. with contagious ovine digital dermatitis lesions and presence of Fusobacterium necrophorum and Dichelobacter nodosus.

Contagious ovine digital dermatitis (CODD) is an important foot disease in sheep, with significant animal welfare and economic implications. It is thought that CODD emerged from bovine digital dermatitis (BDD) via treponemal bacteria. With wildlife species such as elk now suffering a CODD-like disease, it is imperative to clarify these disease etiologies. A large investigation into treponemal association with CODD is warranted. CODD lesions (n = 58) and healthy sheep foot tissues (n = 56) were analyzed by PCR for the three BDD-associated Treponema phylogroups and two other lameness-associated bacteria, Dichelobacter nodosus and Fusobacterium necrophorum. Spirochete culture was also attempted on CODD lesions. "Treponema medium/Treponema vincentii-like," "Treponema phagedenis-like," and Treponema pedis spirochetes were identified in 39/58 (67%), 49/58 (85%), and 41/58 (71%) of CODD lesions, respectively. One or more BDD-associated Treponema phylogroups were detected in 100% of CODD lesions. Healthy foot tissues did not amplify BDD-associated Treponema phylogroup DNA. D. nodosus and F. necrophorum were present in 34/58 (59%) and 41/58 (71%) of CODD lesions and 22/56 (39%) and 5/56 (9%) of healthy foot tissues, respectively. Thirty-two spirochetes were isolated from CODD lesions, with representatives clustering with, and indistinguishable from, each of the three BDD-associated Treponema phylogroups based on 16S rRNA gene comparisons. This study for the first time demonstrates a high-level association for BDD treponeme phylogroups in CODD and their absence from healthy tissues, supporting the hypothesis that BDD treponemes play a primary causative role in CODD and confirming that the specific PCR assays are an effective differential diagnostic tool for CODD.

Identification of inadequate maternal progesterone concentrations in nulliparous dairy heifers and treatment with human chorionic gonadotrophin.

Plasma progesterone concentrations were estimated for 381 nulliparous dairy heifers from eight farms on days 4-6 after insemination. Heifers were synchronised using two treatments of prostaglandin F2α (PGF2α) 11 days apart. Alternate heifers were treated with 1500 IU human chorionic gonadotrophin (hCG) at the time of sampling, and the pregnancy status assessed ~35 days after insemination. Heifers with no corpus luteum (CL; n-30) at the second PGF2α had lower progesterone concentrations (P<0.001) and pregnancy rates (PR; P=0.001) compared with heifers with CL (n=351, defined as cyclic). The risk of no CL increased in heifers <15 months of age (OR=7.5, P<0.001) and with body condition score <2.5 (OR=4.5, P=0.001). Those with no CL were removed from further analysis. The 20 per cent cyclic control heifers with progesterone concentrations ≤2 ng/ml on days 4-6 had lower PRs compared with those with higher concentrations (42 per cent vs 64 per cent, OR=0.3, P=0.01). There was no overall effect of hCG on PR compared with controls (51 per cent vs 60 per cent, P=0.10). However, heifers with high progesterone on days 4-6 (>2 ng/ml) had a lower PR after treatment (51 per cent vs 64 per cent, OR=0.6, P=0.02). Heifers inseminated with sexed (n=18) compared with conventional (n=333) semen had a decreased PR (33 per cent vs 57 per cent, OR=0.2, P=0.01). This study demonstrates that higher plasma progesterone concentrations as early as days 4-6 after insemination have a positive effect on first insemination PR, but there was no beneficial effect of hCG treatment on these days in dairy heifers.

Identifying host pathogenic pathways in bovine digital dermatitis by RNA-Seq analysis.

Digital dermatitis is a painful foot disease compromising welfare in dairy cattle. The disease has a complex multibacterial aetiology, but little is known about its pathogenesis. In this study, gene expression in skin biopsies from five bovine digital dermatitis lesions and five healthy bovine feet was compared using RNA-Seq technology. Differential gene expression was determined after mapping transcripts to the Btau 4.0 genome. Pathway analysis identified gene networks involving differentially expressed transcripts. Bovine digital dermatitis lesions had increased expression of mRNA for α2-macroglobulin-like 1, a protein potentially involved in bacterial immune evasion and bacterial survival. There was increased expression of keratin 6A and interleukin 1ß mRNA in bovine digital dermatitis lesions, but reduced expression of most other keratin and keratin-associated genes. There was little evidence of local immune reactions to the bacterial infection present in lesions.

Antimicrobial resistance in some gram-negative bacteria isolated from the bovine ejaculate.

The bacterial load and degree of antibiotic resistance present in untreated and antibiotic-treated semen samples were investigated in five bulls standing at a cattle-breeding centre. Bacterial load was determined by colony counts from semen samples cultured on brain heart infusion and nutrient agar plates. Antibiotic resistance in these bacteria was assessed by measuring the diameter of bacterial growth inhibition zones around discs containing different concentrations of antibiotics. Representative antibiotic-resistant bacterial isolates were selected for identification. Untreated semen contained few culturable bacteria, and all were completely sensitive to gentamycin, spectinomycin and lincomycin: six of the isolates showed some resistance to tylosin. In semen to which antibiotics had been added as part of the routine production process, two isolates were sensitive to all of the antibiotics tested, and the remainder were resistant to all. Resistant Gram-negative isolates that were identified included Pseudomonas and Stenotrophomonas spp. both in the class Gammaproteobacteria and a Sphingomonas sp. which is in the class Alphaproteobacteria.

California mastitis test scores as indicators of subclinical intra-mammary infections at the end of lactation in dairy cows.

Intramammary infections (IMI) during the dry period can be reduced through the use of dry cow therapy (DCT); in the future, its blanket use is likely to be questioned in the light of public concern regarding the routine use of antibiotics in food producing animals. One possible alternative is to limit DCT to cows with IMI just before drying off, which would require a quick, simple identification of sub-clinical IMI. In the present study we examined quarter milk samples obtained from 240 cows one week before and on the day of drying off, using the California mastitis test (CMT) and for IMI by bacteriological culture. The results indicated that high CMT scores at drying off may be good indicators of IMI: there was a significant association between the frequency of isolation of major pathogens and the CMT score in milk samples obtained one week before (Pearson's χ(2)=27.04, df=4, p<0.001) and those at drying off (Pearson's χ(2)=25.87, df=4, p<0.001).

Energy metabolites in pre- and postpartum dairy cattle as predictors of reproductive disorders.

This study aimed to determine values for selected energy metabolites (non-esterified fatty acid [NEFA], ß-hydroxybutyrate [BHB], urea or urea:BHB ratio), together with a body condition score, associated with an increased risk of cows developing a reproductive disorder and to investigate temporal relationships between predictors and reproductive outcome. A cohort of 98 cows on one farm was monitored weekly from four weeks before to 10 weeks after calving; 89 cows provided sufficient data to calculate commencement of luteal activity (C-LA). Cows with high NEFA × urea (Nu; product of NEFA and urea) values one and three weeks after calving were twice as likely to develop cystic ovarian disease (risk ratio 2). Cows that developed endometritis had high NEFA values one (P=0.02) or four weeks (P=0.04) before calving, or low urea:BHB ratios two weeks before calving, at calving or three weeks after calving (P=0.024, P=0.031 and P=0.001, respectively). Cows that had delayed C-LA had high NEFA values one week after calving (P=0.05) or low urea:BHB ratios three or four weeks after calving (P=0.004 and P=0.003, respectively).

Some factors affecting pregnancy rate in ewes following laparoscopic artificial insemination.

The fertility of 646 ewes and gimmers bred by laparoscopic artificial insemination (LAI) in the autumn of 2006 was investigated using a questionnaire and individual ewe breeding records kept for 13 commercial sheep flocks that used LAI routinely. Overall, the pregnancy rate was 66 per cent, but it was highest in ewes bred for the fourth time. Technical aspects of LAI influenced fertility: pregnancy rates were 70 per cent for ewes bred using frozen semen compared with 58 per cent when fresh semen was used (P≤0.01), and 74 per cent of ewes that travelled to an artificial insemination centre for mating conceived, compared with 62 per cent that remained on their own farm (P<0.01). Higher doses of equine chorionic gonadotrophin (>400 iu) used for oestrus synchronisation reduced pregnancy rates to only 49 per cent (P<0.001). However, the largest effect was associated with shepherds gathering, handling and treating breeding ewes four to six weeks before mating; pregnancy rates were 54 per cent among ewes where this was carried out, compared with 74 per cent for ewes not treated in this way (P<0.01).

The effect of dry cow therapy and internal teat-sealant on intra-mammary infections during subsequent lactation.

Dry cow therapy (DCT), an infusion of antibiotics into the mammary gland at the end of lactation, is widely used for the control of intra-mammary infections (IMI) in the dairy cow. However, increased public health concerns about the use of antibiotics, has led to the search for alternatives to the routine use of antibiotics during drying off. In the present study the effects of three dry cow treatments, two types of DCT and a teat-sealant, on the development of new IMI and clinical mastitis were investigated in 240 cows belonging to two herds (Herd A and Herd B). In Herd A, 60 cows were given one type of DCT (Cloxacillin) and the other 60 cows were given another type of DCT (Framycetin). In Herd B, 60 cows were given teat-sealant and the other herd were not given any treatment. There were significantly more new IMI at calving in control cattle compared to those given teat-sealants (p<0.001) and there were more cases of clinical cases of mastitis in the control group. The number of clinical cases detected in cows given teat-sealant in Herd B were not significantly different from those detected in cows in Herd A given Cloxacillin or Framycetin.

Epidemiology of bovine venereal campylobacteriosis: geographic distribution and recent advances in molecular diagnostic techniques.

Bovine venereal campylobacteriosis (BVC) is a major cause of economic loss to the cattle industries in different parts of the world. Camplylobacter fetus subsp. venerealis (Cfv), the main causative agent of BVC, is highly adapted to the genital tract of cattle and is transmitted by carrier bulls. However, infertility and abortions can also be caused by the intestinal pathogens C. fetus subsp. fetus (Cff), and C. jenuni, which are not venereally transmitted. Bovine venereal campylobacteriosis, caused by Cfv associated with lowered fertility, embryo mortality and abortion, repeated returns to service, reduced pregnancy rates and extended calving intervals, has the highest prevalence in developing countries where natural breeding in cattle is widely practised. The epidemiology, pathogenesis and diagnosis of the disease have been the subject of previous reviews. The main focus of this review is to highlight the epidemiology of this disease with particular reference to geographical distribution and recent advances in molecular diagnostic techniques. It is hoped that further research interest of scientists will be stimulated with a view to finding lasting solutions to the reproductive problems associated with the disease for better livestock productivity, particularly in developing endemic countries.

Mid-piece length of spermatozoa in different cattle breeds and its relationship to fertility.

Recently positive correlation has been found between oxygen consumption (ZO2) in bull spermatozoa and non-return rates and concluded that an increase in ZO2, characteristic of the freeze/thaw process, was possibly associated with mitochondrial membrane damage during this procedure: alternatively, sperm may be hyperactivated through the capacitation-like effects of freezing/thawing. We speculated that the morphology of spermatozoa may be associated with their rate of ZO2 and fertility: for example, sperm mid-piece length where mitochondria are located. Such a relationship has not been investigated before, particularly in context of commercial cattle breeding programmes and bull fertility characteristics. Sperm biometry was performed on ejaculates obtained from 34 bulls representing six breeds: Holstein (yearlings and mature), Friesian, Belgian Blue, Aberdeen Angus, Charolais and Limousin. Five ejaculates were collected from every bull and from each sample a semen smear was fixed and stained with eosin/nigrosin: the mid-piece length of 40 sperm with normal morphology was measured in every sample. Data were analysed by breed, age and within each bull. Significant differences (p<0.01) between ejaculates in 9/34 bulls was found, as well as differences (p<0.001) between individual bulls within the same breed. The average mid-piece length for Aberdeen Angus was 13.35 microm, for Belgian Blues and Limousin around 13.8 microm and for Charolais 13.68 microm: for dairy breeds such as Holstein and Friesian it was about 13.4 microm. The mean value of mid-piece length for breed was compared with their 49 day non-return rate; a negative correlation (r = -0.53) was found in black and white dairy breeds.

Structure and function of the bovine fetomaternal unit in relation to the causes of retained fetal membranes.

Approximately 5 per cent of dairy cows are affected by retained fetal membranes. Retained fetal membranes are an important risk factor for the metritis/endometritis disease complex occurring in early lactation, and costs the UK dairy industry approximately pound16 million annually in lost production. Veterinary clinicians have described the clinical signs, treatment and some associated risk factors of the condition since early Victorian times, and these have not changed over time. Research carried out within the past 20 years suggests that there is an immunological basis for retained fetal membranes. In a normal calving, the maturation of the placenta and its separation from healthy caruncles depends upon incompatibility between maternal and fetal major histocompatibility complex class I expressed on epithelium within the fetomaternal unit. Placental maturation follows stimulation of the maternal immune response and the production of neutrophil-activating factors within the epithelium in the caruncular arcade. This affects the extracellular matrix components within the placentome, breaking down collagen within the chorionic villi and assisting in separation from the caruncle. Factors influencing normal placental maturation include downregulation of antioxidative defence mechanisms against reactive oxygen species, a lower ratio of prostaglandin E(2) to prostaglandin F(2alpha) within the fetomaternal compartments of the placentome, and an elevated steroid hormone receptor status, which reduces the rate of apoptosis occurring in the chorionic epithelium before calving.

Effects of the administration of oxytocin or carbetocin to dairy cows at parturition on their subsequent fertility.

A total of 501 dairy cows were allocated sequentially to be treated immediately after parturition with either 25 iu oxytocin or 35 mg carbetocin, or to be left untreated. Any abnormal parturition, including assisted calving, the birth of twins or dead calves, retained fetal membranes or hypocalcaemia, was recorded, and the cows were examined between 28 and 42 days after calving for endometritis. Pregnancy was diagnosed from 30 days after insemination. The incidence of endometritis was similar (14 per cent, 16 per cent and 19 per cent) and the median intervals from calving to pregnancy were similar (118, 121 and 119 days) for the cows treated with oxytocin, carbetocin or receiving no treatment, respectively. The incidence of endometritis and the median intervals from calving to pregnancy were also similar between the groups for the cows that had an abnormal parturition.

Historical and current perspectives on the treatment, control and pathogenesis of milk fever in dairy cattle.

Milk fever has been recognised in cattle for about 215 years and its clinical signs have not changed since they were described by Victorian veterinary surgeons in the mid-nineteenth century. It was only 80 years ago that abnormal parathyroid gland function was associated with the pathogenesis of the hypocalcaemia characteristic of the disease, and the current basis for its treatment with intravenous calcium salts was established. Although this treatment is effective, most recent research has focused on preventing the disease through an understanding of the endocrine control of extracellular calcium homeostasis. In the 1970s the synthetic vitamin D analogue 1alpha-hydroxycholecalciferol was developed for intramuscular injection before a cow calved, but variable results encouraged other preventive strategies to be considered, including restricting the dietary intake of calcium, and manipulating the dietary cation-anion balance of cows before they calved. Currently, the role of extracellular calcium receptors in the parathyroid gland is under investigation as a preliminary step to devising more effective treatments and/or preventive methods for milk fever.