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R D Murray

Publications and source records attributed to R D Murray.

At least 19 recordsLinked to original sources
PubMed2005

A stereological method for estimating the feto-maternal exchange surface area in the bovine placentome at 135 days gestation.

The feto-maternal relationships within the bovine placentome at 135 days gestation were investigated using unbiased stereology. This provides an estimate of the feto-maternal interface without physically separating these. The functional surface area, the volume of the fetal and maternal components, volumetric tissue shrinkage due to processing, and the feto-maternal surface amplification factor were estimated and quantified in standard units. In this healthy bovine pregnancy there were 105 placentomes with a total volume of 900 ml. The volumetric tissue shrinkage was 24% and the maternal: fetal tissue ratio overall was 0.92. The total feto-maternal exchange surface area was 18.5 m2 with a surface amplification factor of 108.1. Analysis of the coefficient of error from counting different numbers of points within the reference area suggested that 50% and 75% fewer points could be counted to achieve the result obtained by counting approximately 6000 points used in this study.

Animals↗
PubMed2004

Acquired prolactin deficiency (APD) after treatment for Cushing's disease is a reliable marker of irreversible severe GHD but does not reflect disease status.

OBJECTIVE: We have previously reported that acquired prolactin deficiency (APD) is a marker for severe hypopituitarism and observed a high prevalence of APD in patients treated for Cushing's disease. Recovery of GH secretion is recognized to occur in a proportion of patients treated for Cushing's disease after the effects of glucocorticoid excess on GH secretion have subsided. The aim of this study was to investigate further the association between APD, treated Cushing's disease and, in particular, to determine whether recovery of GH secretion may occur in these patients. METHODS: Fifty-seven patients (42 female), in remission after treatment for Cushing's disease, were studied. The cohort comprised 13 patients with, and 44 without APD. APD was defined as a serum prolactin persistently below the detection limit of the assay. Severe GH deficiency was defined as a peak GH response of less than 9 mU/l during a GH stimulation test. Age and gender did not significantly differ between subgroups. RESULTS: Of the 13 patients with APD, a macroadenoma was present in one patient, a microadenoma was present in 10, no lesion was detected in one, and in one patient (treated with an yttrium implant) the size of the tumour was unknown. Of the 28 patients who did not have APD, who were treated with primary surgery a microadenoma was present in 23 and a macroadenoma was present in five. Detailed pituitary imaging was not available in 16 patients who did not have APD, who were treated with primary external XRT. Deficiencies of GH, TSH, LH/FSH (P < 0.0001) and ADH (P = 0.006) status, by conventional testing, were present more frequently in the APD subgroup. In contrast, the prevalence of ACTH deficiency after treatment was not different between the APD and non-APD groups. However, the requirement for additional therapy, targeting the pituitary or adrenal gland, after primary treatment, in those patients not rendered ACTH-deficient, was significantly greater in the APD compared with the non-APD groups (P = 0.003). After pituitary surgery, a significant correlation between peak GH response and interval since remission of Cushing's syndrome was found in the subgroup without APD (r = 0.4, P = 0.04). Four patients who did not have APD, who had documented severe GHD in the immediate postoperative period displayed normalization of GH secretion, when re-tested after a mean interval of 27.2 months. In contrast, no patient with APD after pituitary surgery demonstrated a detectable GH response after up to 132 months of follow-up. No patient with APD showed recovery of prolactin secretion by the time of the most recent measurement (mean 57 months). All 10 patients who developed APD immediately after pituitary surgery had undergone a radical procedure (either a subtotal or total hypophysectomy). In contrast, of 28 patients with Cushing's disease who did not develop APD, only four underwent radical surgery (P < 0.0001). Seven of 14 patients (50%) who underwent a radical operation and two of 20 treated by selective adenomectomy (10%) required additional treatment to achieve control of Cushing's syndrome (P = 0.04). CONCLUSION: In the presence of APD, patients with Cushing's disease do not experience recovery of GH secretion after treatment, even after the effects of glucocorticoid excess subside. In the absence of APD, GH status may normalize after successful surgical treatment. Although a marker for severe hypopituitarism, APD does not indicate success of treatment of Cushing's disease and may be associated with detectable ACTH secretion from residual corticotroph adenoma activity. APD after pituitary surgery for Cushing's disease occurs only after a radical operation. When a selective adenomectomy is not possible, control of Cushing's disease by operation is less frequent and when achieved, is more often at the cost of hypopituitarism. The optimal management of such patients requires further study.

Adenoma↗
PubMed2004

Working practices of cattle foot trimmers used for footcare in dairy cattle compared with those of veterinary surgeons for treatment of lameness in large animal practice.

A questionnaire was sent to 270 veterinary surgeons and 135 cattle foot trimmers, investigating their perceptions on lameness and associated pain, with particular emphasis on dairy cattle. Response rates were 58 and 51%, respectively, but the number of respondents fully answering each question varied. Cattle foot trimming methods, opinions on pain associated with lameness and methods used to control pain were investigated. Responses of both groups were compared. No veterinary surgeon attended more than 50 lame cattle per month. The 'Dutch Method' of foot trimming was always used by 47% of veterinary respondents and 89% of trimmers. Both groups considered lameness to be potentially painful. Orthopaedic shoes were used by 79% of responding veterinary surgeons and 97% of trimmers (P < 0.001) to alleviate weightbearing by diseased digits. Housing lame cows on straw was regularly recommended by approximately one-third of both groups. Around a third of veterinary surgeons used local anaesthetics when treating lame cattle. Only 27% used analgesics when treating lame cattle.

Animals↗
PubMed2002

Generalised additive models and hierarchical logistic regression of lameness in dairy cows.

We examined the relationship between lameness (defined by locomotion score) and four time-related variables using data collected from a study of cattle lameness conducted in the UK from 1998 to 1992. The data were 19,667 locomotion scores for 1790 cows from 27 dairy herds; the four variables were time-from-calving, time of year, parity and time spent in the study. The shape of the relationships between calving and temporal variables and lameness were assessed using loess smoothed terms in a multivariable logistic generalised additive model (GAM). Polynomial relationships derived from the GAM then were included in a Bayesian hierarchical logistic-regression model incorporating between-herd, between-cow and within-cow random effects. The final hierarchical multivariable model showed that the most important variable influencing the probability of lameness was the time of scoring in the study; but, parity, time of year and time-from-calving also were significant. Between-herd and between-cow effects were of roughly equal importance.

Animals↗
PubMed2002

A mixed-effects time-to-event analysis of the relationship between first-lactation lameness and subsequent lameness in dairy cows in the UK.

Data for 611 second-lactation and 251 third-lactation cows were examined using mixed-effects time-to-event models to determine the shape of the hazard, quantify relative risk and estimate herd- and sire-level variation in time to lameness. The semi-parametric Cox and fully parametric Weibull models were suggested from univariable Kaplan-Meier plots. Time to all-lameness, claw-horn lameness and skin lameness were modelled. Explanatory variables were season of current-lactation calving, age at first calving and first-lactation lameness history (whether all-lameness or claw-horn and skin lameness). In mixed-effects models of lactation-2 lameness, previously lame cows had a significantly increased hazard (hazard ratio (HR)=2.0 for all types of lameness and HR=3.2 for claw-horn lameness) compared to those not previously lame. These relationships were less marked in the third lactation. There was little evidence for an effect of age at first calving, whilst possible differences between calving seasons were observed. The hazard function suggested that the rate of lameness was roughly flat across each lactation. Herd-level variation was more evident for infectious foot diseases. The contribution of the sire increased with parity and might be important for sole ulcer and white-line disease.

Age Factors↗
PubMed2002

Some relationships between spirochaete infections and digital dermatitis in four UK dairy herds.

Digital dermatitis, presenting as a focal necrotic dermatitis on the skin of cows' feet adjacent to the interdigital space, has been associated with dermal infection by spirochaetes. Lesions cause severe, transient lameness. An enzyme-linked immunoassay (ELISA) was used to measure IgG(2) antibody titres against three different spirochaetes: USA bovine Treponema isolates 1-9185MED and 2-1498, and a UK strain of Borrelia burgdorferi B31. Logistic models were used to describe lesion prevalence in terms of the antibody titres, herd and milking status, year, lactation number, and yield. The antibody titres and milking status (P<0.001) dominated the logistic fits, with the other variables adding little. Generalised linear models were used to describe the antibody titres in terms of the presence or absence of lesions, herd, year, lactation number, and yield. The presence or absence of lesions had the most significant effect for all three antibodies (P<0.001). Neither the herd effects nor the effects due to lactation number or yield showed consistent patterns.

Animal Husbandry↗
PubMed2002

Quantitative unbiased estimates of endometrial gland surface area and volume in cycling cows and heifers.

Entire reproductive tracts were removed from seven normal healthy heifers and qualitative unbiased estimates made of endometrial gland volume density and glandular surface density. After examining approximately 55 microscopic fields of endometrium from each tract, a mean glandular surface density value of 10.2 mm(2)/mm(3) (CE 3.1%) was obtained. The stereological method was then employed in optimising the design of the main study. The endometrial height was measured for 17 healthy cycling heifers and 19 similar cows. Subsequently, unbiased estimates were made of intercaruncular endometrial gland volume per unit surface for all cattle were investigated; differences between heifers and cows generally, and the possible effect of the follicular and luteal phases of the oestrous cycle were compared. The mean surface area of glands per unit area of endometrium at the intercaruncular site in heifers and cows was approximately 18 mm(2)/mm(2) in the follicular phase and 26 mm(2)/mm(2) in the luteal phase, figures similar to the gland area found in women. The intercaruncular gland volume increased significantly, by about 30% during the luteal phase of the bovine oestrous cycle in heifers, from 0.01 to 0.13 per mm(3). The differences in endometrial anatomy between site of sampling and either follicular or luteal phases of the oestrous cycle were always more significant in heifers than cows. The endometrial thickness in cows was always greater than for heifers, irrespective of the site of sampling. It was concluded that the intercaruncular endometrium of cattle was far more active physiologically than recognised previously.

Animals↗
PubMed2002

Spinal irradiation impairs the osteo-anabolic effects of low-dose GH replacement in adults with childhood-onset GH deficiency.

BACKGROUND AND OBJECTIVE: Both adult- and childhood-onset GH-deficient adults are prone to osteopenia. Studies of GH replacement have, for the most part, demonstrated increases in bone mineral density (BMD). Previous studies have, however, used GH doses in excess of those currently used in low-dose titration regimens aimed at normalizing the serum IGF-I level. Furthermore, the effect of GH on the lumbar spine that has been irradiated during treatment of childhood cancer is unknown. PATIENTS: Thirty-two adult patients with childhood-onset GH deficiency were subdivided according to whether or not they had received spinal irradiation in childhood. The cohort in whom the spine had not been irradiated was comprised of 17 patients (seven male, 10 female), median age 29.8 years (range 20.6--40.8), the median age at primary pathological diagnosis being 9 years (range 4--16). The cohort who received spinal irradiation was composed of 15 patients (seven male, eight female), median age 22.9 years (range 16.5--40.3), with a median age at craniospinal irradiation of 9 years (range 2--16). MEASUREMENTS: At baseline, BMD was assessed at the lumbar spine and femoral neck by DXA, and at the ultradistal and distal radius by SXA. The patients were then commenced on GH replacement, titrating the dose at 4--6-weekly intervals to normalize the serum IGF-I level. BMD scans were reassessed following at least 1 year of GH replacement therapy. The mean duration of GH therapy was 1.68 plus minus 0.52 years. RESULTS: BMD was significantly reduced, compared to the reference data, at all four sites measured in both the spinally irradiated and unirradiated groups. No significant difference was observed between the subgroups with respect to lumbar spine BMD (P = 0.64). In the cohort who did not receive spinal irradiation, an increase in BMD of 3.5% above baseline was observed at the lumbar spine (P = 0.018), 13/17 patients showing a positive increment in lumbar spine BMD. No significant changes in BMD were observed at any other site within this cohort, or at any site in the patients who received spinal irradiation. A significantly greater change in lumbar spine BMD was observed in the unirradiated spine cohort compared with the spinally irradiated cohort (P = 0.018). No differences in response were demonstrated at the other sites studied between the two subgroups. CONCLUSIONS: We have demonstrated an increase in lumbar spine BMD with long-term (mean 1.78 +/- 0.55 years) GH therapy in adults with childhood-onset GH deficiency, who have not received spinal irradiation, when GH was administered by a titration regimen aimed at normalizing the serum IGF-I level. No improvements were observed at the femoral neck, ultradistal or distal radius. Patients who had received spinal irradiation during childhood did not present with a reduction in spinal BMD in excess of that observed in the nonirradiated cohort. The spinally irradiated group were, however, resistant to the osteo-anabolic effects of GH, which we propose reflects the capacity of radiation-induced damage to suppress the skeletal response.

Adolescent↗
PubMed2002

Low-dose GH replacement improves the adverse lipid profile associated with the adult GH deficiency syndrome.

OBJECTIVE: Adult growth hormone deficiency (AGHD) is associated with an adverse lipid profile. The majority of previous studies of GH replacement have used supraphysiological doses and reported favourable changes in the lipid profile. Whether this beneficial effect is the result of pharmacological GH therapy, or occurs in response to low-dose GH replacement aimed at normalization of the serum IGF-I, has not been fully elucidated. STUDY DESIGN: We studied 67 patients with GH deficiency using a low-dose individualized GH replacement regimen. GH was commenced at a dose of 0.27 mg/day and the GH dose titrated until the serum IGF-I was normalized. Serum lipids were assessed at baseline, 12 and 24 months. RESULTS: A reduction in total cholesterol (TC) was observed at 12 (6.01 vs. 5.77 mmol, P = 0.04) and 24 months (6.01 vs. 5.56, P = 0.09). The reduction in LDLC failed to reach significance at 12 months (3.97 vs. 3.8, P = 0.09), but was significant at 24 months (3.97 vs. 3.50, P = 0.02). Levels of HDLC did not change significantly at 12 or 24 months. Significant improvements in the TC/HDLC ratio were observed at both 12 (5.68 vs. 5.29, P = 0.01) and 24 months (5.68 vs. 4.86, P = 0.007). A significant fall in triglycerides (TG) was present at 12 months (2.07 vs. 1.83, P = 0.01), and was maintained at 24 months, but was no longer significant (2.07 vs. 1.89, P = 0.28). At 12 months there was no correlation between improvements in lipid parameters and either the change in IGF-I SD score or the GH dose. Using multivariate analysis the change in TC, LDLC and the TC/HDLC ratio with 12 months GH replacement were determined by the baseline TC, LDLC and TC/HDLC levels (R2 = 0.18, P = 0.004; R2 = 0.20, P = 0.006; and R2 = 0.33, P < 0.0001), respectively. CONCLUSIONS: Low-dose individualized GH replacement aimed at normalization of the serum IGF-I is associated with significant improvements in TC, LDLC, TGs and the TC/HDLC ratio. The greatest improvements are observed in patients with the most adverse lipid profiles at baseline. Improvements are independent of changes in the IGF-I SDS and GH dose.

Adult↗
PubMed2002

Timing of onset of growth hormone deficiency is a major influence on insulin-like growth factor I status in adult life.

OBJECTIVE: Several reports have suggested that IGF-I levels in patients with childhood-onset (CO) GH deficiency are lower than those observed in patients with adult-onset (AO) GH deficiency. However, these reports are unsatisfactory as there are several differences between the cohorts studied other than the timing of onset of GH deficiency; in particular, the patients were not matched for equal severity of GH deficiency. We have pursued this question further by examining the IGF-I standard deviation score (SDS) in patients with CO and AO GH deficiency, with equal degrees of severity of GH deficiency, as defined by the peak GH response to the insulin tolerance test (ITT). PATIENTS AND MEASUREMENTS: IGF-I SDS were compared in 146 non acromegalic patients (69 male), aged 15.7-76.6 years (median 33.4 years), bone mass index (BMI) 27.8 +/- 5.8 kg/m2, with severe GH deficiency (peak GH response < 9 mU/l to insulin-induced hypoglycaemia). Patients were subdivided by timing of onset of GH deficiency and the peak GH response to the ITT (GH response < or = 1 mU/l, group 1; > 1-3 mU/l, group 2; > 3-6 mU/l, group 3; > 6-8.9 mU/l, group 4). RESULTS: The IGF-I SDS (mean value +/- SD) in the CO group (n = 63) as a whole was significantly lower than that found in the AO group (n = 83) (-3.7 +/- 2.8 vs.-1.55 +/- 2.2, respectively; P < 0.0001). Despite this, there was no significant difference in the peak GH response to an ITT between the two cohorts (2.8 +/- 2.3 mU/l in the AO cohort and 2.6 +/- 2.2 mU/l in the CO cohort; P = 0.5). When the cohorts were subdivided by severity of GH deficiency, there remained a significant difference in IGF-I SDS in groups 1 (P < 0.0001), 2 (P = 0.05) and 3 (P < 0.05), but there was no significant difference between the AO and CO cohorts in group 4. The peak GH response to an ITT was similar in the AO and CO cohorts in all groups (P = 0.8, 0.8, 0.9 and 0.3 in groups 1-4, respectively). Although increasing severity of hypopituitarism was associated with a decline in IGF-I SDS in the CO cohort (P < 0.01), this was not the case in the AO cohort (P = 0.3). CONCLUSION: These data support the hypothesis that there is an innate difference between adult patients with either CO or AO GH deficiency that cannot be explained solely by variation in the severity of GH deficiency. A possible explanation is that childhood GH deficiency programmes the subsequent relationship between GH and IGF-I in adult life or that the body composition changes, which are more severe in AO GH deficiency, influence IGF-I status.

Adolescent↗
PubMed2002

The effect of long-term untreated growth hormone deficiency (GHD) and 9 years of GH replacement on the quality of life (QoL) of GH-deficient adults.

BACKGROUND: Quality of life (QoL) is reduced in GH-deficient adults compared with the normal population. Further support for the role of GH in the maintenance of QoL is derived from short-term studies of GH replacement in severely GH-deficient adults; these have predominantly reported beneficial effects, although the degree of improvement has often been modest. To date, however, there are few data to demonstrate whether this beneficial effect on QoL is maintained in the long term. PATIENTS AND METHODS: This study consisted of the follow-up of 85 GH-deficient adults who completed the Nottingham Health Profile (NHP) and the Psychological General Well-Being Schedule (PGWB) self-rating questionnaires in 1992, as part of a 12-month double-blind randomized study of GH replacement. In 2001 we attempted to contact all 85 patients and asked them to complete the two questionnaires again. Follow-up data were obtained in 61 patients. The findings were analysed according to whether the individual had received GH continuously since completion of the initial study, received no further GH replacement, or received GH replacement for only part of the intervening time. Both the NHP and the PGWB give a total score and subsection scores for six specific areas of QoL. A high score correlates with increased morbidity in the NHP, and with reduced morbidity in the PGWB. RESULTS: Fifty-nine patients completed the NHP at both time points. The patients who continued GH (n = 17) had significantly greater morbidity at baseline than patients who opted to discontinue therapy (n = 27), as reflected by the higher scores overall (5.7 +/- 4.0 vs. 2.8 +/- 3.5; P = 0.01) and in the energy subsection (47.0 +/- 34.7 vs. 13.2 +/- 28.6; P < 0.001). Over the study period energy levels improved in the patients who remained on GH therapy (47.0 +/- 34.7 vs. 25.7 +/- 31.0; P = 0.04). By contrast, a deterioration in the physical mobility subsection (2.4 +/- 5.4 vs. 8.2 +/- 16.7; P = 0.04) occurred in the patients who did not continue GH therapy, and no change occurred in the energy subsection. In the 36 patients who completed the PGWB significant differences were observed at baseline between patients who received GH replacement continuously (n = 10) and those who discontinued therapy (n = 21) in the overall score (67.2 +/- 14.1 vs. 86.8 +/- 14.7; P = 0.001); and in the subsections for anxiety (P = 0.04), depression (P = 0.04), well-being (P = 0.001), self-control (P = 0.04) and vitality (P < 0.001); the greater morbidity at baseline being observed in the patients who continued GH replacement. In the patients receiving GH continuously for 9 years the vitality subsection score improved significantly (7.7 +/- 2.4 vs. 12.5 +/- 3.2; P = 0.003), whereas no change in vitality score occurred in patients who did not continue GH therapy. The change in the energy subsection of the NHP and vitality subsection of the PGWB over the 9 years of the study were significantly different between the patients who opted to continue GH replacement and those who discontinued therapy (P = 0.008 and P < 0.001, respectively). CONCLUSION: During this 9-year study, small but significant declines in health were observed in GH-deficient adults who remained untreated. By contrast, the patients who received GH continuously experienced improvements in energy levels while all other areas of QoL were maintained. The beneficial effects of GH on QoL are therefore maintained with long-term GH replacement and obviate the reduction in QoL seen over time in untreated GH-deficient adults.

Adult↗
PubMed2002

Comparison of external and internal pelvic measurements of Belgian Blue cattle from sample herds in Belgium and the United kingdom.

Measurements describing pelvic conformation of pedigree Belgian Blue cows were obtained from a sample of nine herds in Flanders, Belgium, comprising 111 adult breeding cows, and from 11 herds in the United Kingdom comprising 108 similar cows. All herds in the Belgian sample (111 cows) managed parturition by elective caesarian section as did seven herds (56 cows) in the UK sample; the remainder of UK herds (52 cows) allowed cows the opportunity to calve naturally per vagina before resorting to caesarian section. The data described the external and internal measurements, and pelvic area characteristic of this breed, irrespective of the different selection pressures applied over a number of years to this breed through variation in farm management and market forces present in either country. From these data, generalized linear models were constructed to predict pelvic area; they correctly identified cows with either small or large pelvic areas. There were no significant differences in pelvic conformation between cattle bred either in Belgium or the UK, although those cows bred in herds where natural calving was allowed to take place had significantly larger internal pelvic height (p < 0.05) and area (p < 0.05) than other Belgian Blue cows. The correlation coefficients between internal pelvic height and width and external pelvic measurements were significant (p < 0.001). These results might facilitate the selection of breeding cows with larger pelvic area so that a higher proportion of cows can calve naturally than currently occurs. However, selection for other traits such as relatively low birth weight combined with higher weaning weight should be carried out at the same time.

Animals↗
PubMed2002

A systematic compilation and classification of the literature on lameness in cattle.

This paper presents the first systematic review of the literature on lameness in cattle. It identifies, tabulates and classifies relevant published work and was conducted using electronic reference databases (BIDS ISI, BIOSIS, MEDLINE and the CAB Abstracts CD-ROM). A total of 1373 unique references were obtained from 1981 to 2000, of which 914 were written in the English language. A written search protocol was designed to ensure transparency and repeatability. Pilot studies were undertaken to create search terms that minimised bias and ensured relevance. Electronic files of the search terms allow the database to be updated in future. A further 93 references were included from the most recent international conference on lameness giving a total of 1007 English language references. The systematic review process is described, including a method of classifying papers according to their study design and statistical analysis, and it is hoped that other veterinary researchers will conduct similar reviews in their fields. The compiled and classified references are available as a searchable database through the web-sitehttp://cattle-lameness.dhs.org/. The review may be used in several ways; to identify practical interventions to reduce lameness in dairy cows and to use the resultant web-site as the basis of a decision support system for farmers, veterinarians and advisors.

Animals↗
PubMed2002

GH-deficient survivors of childhood cancer: GH replacement during adult life.

Childhood survivors of cancer are prone to a number of adverse sequelae related to the therapeutic interventions undertaken to achieve remission. The endocrine system is frequently affected; hypothalamo-pituitary dysfunction, in particular GH deficiency, is common after cranial irradiation. It is unclear to what extent GH deficiency contributes to the abnormalities observed in adult survivors of childhood cancer, and whether GH replacement reverses these anomalies. We compared 27 GH-deficient survivors of childhood cancer with 27 adult age- and sex-matched controls and went on to replace GH in the patient group to determine whether GH resulted in improvements of the baseline abnormalities. The GH-deficient survivors of childhood cancer had an adverse lipid profile (total cholesterol, 5.4 vs. 4.6 mM, P = 0.004; high-density lipoprotein cholesterol, 1.05 vs. 1.6 mM, P < 0.001; and triglycerides, 1.3 vs. 1.0 mM, P < 0.001) and were osteopenic (lumbar spine z-score, -1.53 vs. -0.31 SD score, P < 0.001; femoral neck z-score, -1.23 vs. -0.27 SD score, P = 0.02); additionally, the female subgroup had an increased percentage body fat (43.6 vs. 32.8%, P = 0.016). In keeping with the selection criterion, quality of life in the patient cohort, relative to the healthy controls, was severely impaired [adult GH-deficiency assessment (AGHDA), 15.5 (range, 8-25) vs. 1 (range, 0-19), P < 0.0001; psychological general well-being schedule, 67.5 (range, 18-86) vs. 89.0 (range, 51-104), P < 0.0001]. After 12 months of GH replacement, small (but significant) improvements were observed in body composition in the male subgroup (waist-hip ratio, 0.871 vs. 0.863, P < 0.05); and in the female cohort, total cholesterol (6.0 vs. 5.2 mM, P = 0.01) and triglyceride (2.1 vs. 1.4 mM, P = 0.01) levels fell. Bone mineral density improved in only one of the four sites studied (ultradistal radius, -1.21 vs. -1.09, P = 0.048) after a median duration of GH therapy of 18 months. Quality of life improved dramatically by 3 months (AGHDA, 15.5 vs. 10.0, P < 0.001), and the improvement was maintained at 12 months (AGHDA, 15.5 vs. 9.0, P < 0.001). Importantly, there was no clinical suggestion of tumor recurrence during the 12 months of GH replacement. The minor improvements observed in body composition, the lipid profile, and bone mineral density in GH-deficient adult survivors of childhood cancer after 12-18 months of physiological GH replacement suggest that GH deficiency may not be the major etiological factor in their pathogenesis; the converse seems to be true for the quality of life status of these individuals. We propose that, as in patients with hypopituitarism caused by pituitary disease, the main indication for GH replacement in GH-deficient survivors of childhood cancer should be severe impairment of quality of life.

Adolescent↗
PubMed2001

Some aspects of immunology of the bovine uterus related to treatments for endometritis.

Endometritis in breeding cattle occurs during the postpartum period, and is associated primarily with contamination of the reproductive tract involving Arcanobacter pyogenes (formerly Actinomyces pyogenes) together with Gram-negative anaerobes. Polymorphonuclear inflammatory cells (PMNs) contribute partly to the defense mechanisms against micro-organisms contaminating the vagina and uterine lumen, whose phagocytic activity depends on bacterial opsonisation by humoral antibodies; significant numbers of lymphocytes are also present. Whilst leukocyte numbers in the uterine lumen are relatively high during metoestrus and dioestrus compared to other phases of the oestrous cycle, their functional activity is unaffected. Humoral antibody concentrations in the reproductive tract are stimulated following exposure to local antigen, and the response is site dependent; of the several different classes of immunoglobulins, IgG predominates in the uterus and IgA the vagina. Only a portion of the total IgG1 found on the uterine lumen is synthesised locally in the endometrium, the remainder and all of the IgG2 is derived from the local uterine blood supply. Generally, concentrations of immunosuppressant proteins present in the uterine lumen increase under progesterone dominance, and these inhibit lymphocyte proliferation, making the uterus more susceptible to infection. The relationship between uterine susceptibility to micro-organism contamination and the luteal phase of the oestrous cycle is still unclear. Intrauterine infusion of immunomodulators such as E. coli lipopolysaccharides (LPS) or oyster glycogen, in healthy cows and those with endometritis, stimulates leukocytes to migrate into the uterine lumen. At a dosage rate of 100 microg, lipopolysaccharides are not absorbed by the healthy endometrium and do not alter the oestrous cycle length. It is unknown, whether a similar dose can be absorbed through an inflamed endometrium in naturally occurring cases of endometritis to cause systemic illness. Currently, prostaglandin F2alpha is recommended for treating endometritis in both cycling and non-cycling cows, but its mode of action in non-cycling cows is not fully understood. The efficacy of endometritis treatment using an intrauterine infusion of an immunomodulator in cases occurring naturally has not been determined on a large scale.

Animals↗
PubMed2001

Difference in the respiratory variation between pulmonary venous and mitral inflow Doppler velocities in patients with constrictive pericarditis with and without atrial fibrillation.

OBJECTIVES: The goal of this study was to evaluate the difference in the respiratory change from expiration to inspiration (%E) between pulsed Doppler mitral inflow (MV) and pulmonary venous flow (PV) velocities in patients with constrictive pericarditis (CP) and to describe the influence of atrial fibrillation (AF). BACKGROUND: The difference in %E between MV and PV velocities as well as the influence of AF on %E has not been well described. METHODS: Pulsed-wave Doppler transesophageal echocardiography (TEE) was performed with respiratory monitoring in 31 patients with CP and sinus rhythm (SR) and in 10 patients with CP and AF. The MV early (E) and late diastolic (A) velocities and their velocity time integral (VTI) as well as PV systolic (S) and diastolic (D) velocities and their VTI were measured. RESULTS: Regardless of the cardiac rhythm: 1) The MV-E velocity and E-VTI as well as PV-D velocity and D-VTI significantly decreased from expiration to inspiration; 2) the %E in PV-D velocity (27% in SR and 35% in AF) and D-VTI (38% in SR and 45% in AF) was significantly greater than that in MV-E velocity (18% in SR and 15% in AF) and E-VTI (21% in SR and 19% in AF), respectively; 3) the PV S/D and S/D-VTI significantly increased from expiration to inspiration. CONCLUSIONS: A significant respiratory variation was observed in both MV and PV velocities in CP, not only in patients with SR but also in those with AF. Moreover, the %E was greater in the PV velocities than it was in the MV velocities. Evaluation of the %E in the PV velocities using TEE can be a sensitive diagnostic strategy for evaluation of patients with CP, even in patients with AF.

Atrial Fibrillation↗