Primary osteolysis syndromes: beware of difficult airway.

BACKGROUND: Primary osteolysis syndromes represent a number of rare conditions characterized by destruction and resorption of bone that is unrelated to neoplasia, infection, or trauma. AIM: To characterize the periprocedural course of patients with primary osteolysis syndrome undergoing procedures that require anesthesia care. METHODS: The medical records database from our institution was searched from 1976 to 2013 to identify patients with primary osteolysis syndromes who received anesthesia care. We reviewed demographic characteristics, comorbidities, and perioperative course of patients with different forms of primary osteolysis. A systematic review of the literature was performed to identify reports describing the anesthetic management of patients with these conditions. RESULTS: We identified 11 patients with a primary osteolysis syndrome who received 111 anesthetics. The patients' ages at the time of surgery ranged from 3 to 62 years. Difficult airway management was a common finding. On preoperative examination, difficulty with endotracheal intubation was predicted in 8 of 11 patients. Three patients had preexisting tracheostomies. One patient required multiple awake fiberoptic intubations. Another two patients where successfully intubated early in life via direct laryngoscopy, but eventually required awake fiberoptic intubations as the disease process caused progressive distortion of airway structures. Intraoperative complications were absent. In the postoperative period, three patients required prolonged mechanical ventilation due to airway swelling, respiratory failure, and infection. CONCLUSIONS: Airway management may be challenging in patients with primary osteolysis syndromes. Because the osteolytic process advances with aging and craniofacial dysmorphism may progressively worsen, the airway should always be reassessed before surgery with an appropriate strategy for potentially difficult intubation. In all patients with primary osteolysis, a potential for pathologic fracture must be considered and careful intraoperative positioning is warranted.

Expression of candidate genes for residual feed intake in Angus cattle.

Residual feed intake (RFI) has been adopted in Australia for the purpose of genetic improvement in feed efficiency in beef cattle. RFI is the difference between the observed feed intake of an animal and the predicted feed intake based on its size and growth rate over a test period. Gene expression of eight candidate genes (AHSG, GHR, GSTM1, INHBA, PCDH19, S100A10, SERPINI2 and SOD3), previously identified as differentially expressed between divergent lines of high- and low-RFI animals, was measured in an unselected population of 60 steers from the Angus Society Elite Progeny Test Program using quantitative real-time PCR. Results showed that the levels of gene expression were significantly correlated with RFI. The genes explain around 33.2% of the phenotypic variance in RFI, and prediction equations using the expression data are reasonably accurate estimators of RFI. The association of these genes with economically important traits, such as other feed efficiency-related traits and fat, growth and carcass traits, was investigated as well. The expression of these candidate genes was significantly correlated with feed conversion ratio and daily feed intake, which are highly associated with RFI, suggesting a functional role for these genes in modulating feed utilisation. The expression of these genes did not show any association with average daily gain, eye muscle area and carcass composition.

Skin tumours in the West of Scotland renal transplant population.

BACKGROUND: Organ transplant recipients have an increased risk of skin cancers. A specialist dermatology clinic for renal transplant recipients (RTRs) was established in 2005. OBJECTIVES: To analyse the type and incidence of skin cancers in prevalent patients in the West of Scotland after renal transplant, and to analyse the impact of the time since transplant and the immunosuppression regimen. METHODS: Skin cancer data for RTRs attending the transplant dermatology clinic over a 38-month period were collected and recorded in the West of Scotland electronic renal patient record. Skin cancer data were intrinsically linked to each individual's transplant and immunosuppression data. RESULTS: Overall, 610 patients attended. The median follow-up time from the date of first transplant was 10 years. Ninety-three patients (15.2%) had experienced a total of 368 skin cancers since transplant, and the prevalence increased with time since transplant. Basal cell carcinomas (BCCs) occurred in 74 patients (12.1%) and squamous cell carcinomas (SCCs) in 42 patients (6.9%). Three patients (0.5%) had experienced a melanoma. The SCC:BCC ratio was 0.7. Survival analysis showed significant reduction in the time to develop skin cancer in patients transplanted from 1995 onwards (P < 0.0001) and in patients who had been on triple immunosuppressant therapy at 1 year after transplant, compared with dual therapy (P < 0.0001). CONCLUSIONS: This is the first study of skin cancer in prevalent Scottish RTRs. The incidence of skin cancer is high and appears to have a direct relationship to the overall burden of immunosuppression. The SCC:BCC ratio, which is lower than reports from other centres, deserves further scrutiny.

Reduced bone density and osteoporosis associated with a polymorphic Sp1 binding site in the collagen type I alpha 1 gene.

Osteoporosis is a common disease with a strong genetic component, characterized by reduced bone mass and increased fracture risk. Current evidence suggests that the inheritance of bone mass is under polygenic control but the genes responsible are poorly defined. Type I collagen is the major protein of bone encoded by the COLIA1 and COLIA2 genes. While these are strong candidates for the genetic regulation of bone mass, no abnormality of either gene has so far been defined in osteoporosis. In this study, we describe a novel G-->T polymorphism in a regulatory region of COLIA1 at a recognition site for the transcription factor Sp1(7) that is significantly related to bone mass and osteoporotic fracture. G/T heterozygotes at the polymorphic Sp1 site (Ss) had significantly lower bone mineral density (BMD) than G/G homozygotes (SS) in two populations of British women and BMD was lower still in T/T homozygotes (ss). The unfavourable Ss and ss genotypes were over-represented in patients with severe osteoporosis and vertebral fractures (54%), as compared with controls (27%), equivalent to a relative risk of 2.97 (95% confidence interval 1.63-9.56) for vertebral fracture in individuals who carry the 's' allele. While the mechanisms that underlie this association remain to be defined, the COLIA1 Sp1 polymorphism appears to be an important marker for low bone mass and vertebral fracture, raising the possibility that genotyping at this site may be of value in identifying women who are at risk of osteoporosis.

Global gene expression profiling reveals genes expressed differentially in cattle with high and low residual feed intake.

Feed efficiency is an economically important trait in beef production. It can be measured as residual feed intake. This is the difference between actual feed intake recorded over a test period and the expected feed intake of an animal based on its size and growth rate. DNA-based marker-assisted selection would help beef breeders to accelerate genetic improvement for feed efficiency by reducing the generation interval and would obviate the high cost of measuring residual feed intake. Although numbers of quantitative trait loci and candidate genes have been identified with the advance of molecular genetics, our understanding of the physiological mechanisms and the nature of genes underlying residual feed intake is limited. The aim of the study was to use global gene expression profiling by microarray to identify genes that are differentially expressed in cattle, using lines genetically selected for low and high residual feed intake, and to uncover candidate genes for residual feed intake. A long-oligo microarray with 24 000 probes was used to profile the liver transcriptome of 44 cattle selected for high or low residual feed intake. One hundred and sixty-one unique genes were identified as being differentially expressed between animals with high and low residual feed intake. These genes were involved in seven gene networks affecting cellular growth and proliferation, cellular assembly and organization, cell signalling, drug metabolism, protein synthesis, lipid metabolism, and carbohydrate metabolism. Analysis of functional data using a transcriptional approach allows a better understanding of the underlying biological processes involved in residual feed intake and also allows the identification of candidate genes for marker-assisted selection.

Presence of beta human papillomaviruses in nonmelanoma skin cancer from organ transplant recipients and immunocompetent patients in the West of Scotland.

BACKGROUND: Nonmelanoma skin cancer (NMSC) has been linked to cutaneous human papillomaviruses of the genus beta (betaPV). OBJECTIVES: We sought to assess the presence of betaPV in NMSC biopsies from a group of Scottish skin cancer patients, both immunocompetent (IC) patients and immunosuppressed (IS) organ transplant recipients. METHODS: One hundred and twenty-one paraffin-embedded skin tumours (27 actinic keratosis, 41 intraepidermal carcinoma, 53 squamous cell carcinoma) and 11 normal skin samples were analysed for the presence of betaPV by a polymerase chain reaction-reverse hybridization assay designed to detect the presence of the 25 known betaPV genotypes. RESULTS: In IC patients, betaPV was detected in 30 of 59 (51%) tumours and two of 11 (18%) normal skin samples (P = 0.046). In IS patients, betaPV was found in 27 of 62 (44%) tumours; no normal skin samples were available for comparison. The most frequently found genotypes were HPV-24, HPV-15 and HPV-38. Of those tumours infected with betaPV, 28 of 57 (49%) were infected with more than one genotype (range 2-8). Tumours from IS patients were from a younger age group (mean age 57.4 years) than IC patients (mean age 73.8 years). Multiple infections were more common in tumours from IC patients (21 of 30; 70%) compared with those from IS patients (seven of 27; 26%) (P < 0.001). In the IC group, age did not appear to influence the distribution of single and multiple infections whereas in IS patients the proportion of multiple infections to single infections increased with age. There were no multiple infections in normal skin. CONCLUSIONS: A wide spectrum of betaPV types was detected in our samples. Further characterization of betaPV in vivo is needed in order to determine the mechanisms by which the virus contributes to cutaneous carcinogenesis.

Phenotypic relationships among methane production traits assessed under ad libitum feeding of beef cattle.

Angus cattle from 2 beef cattle projects in which daily methane production (MPR) was measured were used in this study to examine the nature of the relationships among BW, DMI, and methane traits of beef cattle fed ad libitum on a roughage diet or a grain-based feedlot diet. In both projects methane was measured using the GreenFeed Emission Monitoring system, which provides multiple short-term breath measures of methane production. The data used for this study were from 119 Angus heifers over 15 d on a roughage diet and 326 Angus steers over 70 d on a feedlot diet. Mean (±SD) age, BW, and DMI were 372 ± 28 d, 355 ± 37 kg, and 8.1 ± 1.3 kg/d for the heifers and 554 ± 86 d, 577 ± 69 kg, and 13.3 ± 2.0 kg/d for the steers, respectively. The corresponding mean MPR was 212 g/d for heifers and 203 g/d for steers. Additional traits studied included methane yield (MY; MPR/DMI), methane intensity (MPR/BW), and 3 forms of residual methane production (RMP), which is a measure of actual minus predicted MPR. For RMP, RMP, and RMP predicted MPR were obtained by regression of MPR on BW, on DMI, and on both DMI and BW, respectively. The 2 data sets were analyzed separately using the same statistical procedures. For both feed types the relationships between MPR and DMI and between MPR and BW were both positive and linear. The correlation between MPR and DMI was similar to that between MPR and BW, although the correlations were stronger for the roughage diet ( = 0.75 for MPR vs. DMI; = 0.74 for MPR vs. BW) than the grain-based diet ( = 0.62 for MPR vs. DMI; = 0.66 for MPR vs. BW). The correlation between MY and DMI was negative and moderate for the roughage ( = -0.68) and grain-based ( = -0.59) diets, a finding that is different from the nonsignificant correlations reported in studies of cattle on a restricted roughage diet. The 3 RMP traits were strongly correlated ( values from 0.76 to 0.99) with each other for both the roughage and the grain-based diets, which indicates that using RMP to lower MPR could provide a result similar to using RMP in cattle. As feed intake (DMI) is more difficult to measure than BW, this result implies that under ad libitum feeding situations in which DMI cannot be measured, RMP can be used to identify higher- or lower-RMP animals with similar levels of effectiveness as RMP.

Optimizing test procedures for estimating daily methane and carbon dioxide emissions in cattle using short-term breath measures.

Respiration chambers are considered the reference method for quantifying the daily CH production rate (MPR) and CO production rate (CPR) of cattle; however, they are expensive, labor intensive, cannot be used in the production environment, and can be used to assess only a limited number of animals. Alternative methods are now available, including those that provide multiple short-term measures of CH and CO, such as the GreenFeed Emission Monitoring (GEM) system. This study was conducted to provide information for optimizing test procedures for estimating MPR and CPR of cattle from multiple short-term CH and CO records. Data on 495 Angus steers on a 70-d ad libitum feedlot diet with 46,657 CH and CO records and on 121 Angus heifers on a 15-d ad libitum roughage diet with 7,927 CH and CO records were used. Mean (SD) age and BW were 554 d (SD 92) and 506 kg (SD 73), respectively, for the steers and 372 d (SD 28) and 348 kg (SD 37), respectively, for the heifers. The 2 data sets were analyzed separately but using the same procedures to examine the reduction in variance as more records are added and to evaluate the level of precision with 2 vs. 3 min as the minimum GEM visit duration for a valid record. The moving averages procedure as well as the repeated measures procedure were used to calculate variances for both CH and CO, starting with 5 records and progressively increasing to a maximum of 80 records. For both CH and CO and in both data sets, there was a sharp reduction in the variances obtained by both procedures as more records were added. However, there was no substantial reduction in the variance after 30 records had been added. Inclusion of records with a minimum of 2-min GEM visit duration resulted in reduction in precision relative to a minimum of 3 min, as indicated by significantly ( < 0.05) more heterogeneous variances for all cases except CH4 in steers. In addition, more records were required to achieve the same level of precision relative to data with minimum GEM visit durations of 3 min. For example, in the steers, 72% reduction in initial variance was achieved with 30 records for both CH and CO when minimum GEM visit duration was 3 min, relative to 45 records when data with a minimum visit duration of 2 min were included. It is concluded from this study that when using records of multiple short-term breath measures of CH or CO for the computation of an animal's MPR or CPR, a minimum of 30 records, each record obtained from a minimum GEM visit duration of 3 min, are required.

Associations among methane emission traits measured in the feedlot and in respiration chambers in Angus cattle bred to vary in feed efficiency.

The objective of the study was to evaluate associations among animal performance and methane emission traits under feedlot conditions and in respiration chambers in Angus cattle bred to vary in residual feed intake (RFI), which is a measure of feed efficiency. Fifty-nine cattle were tested for feedlot RFI, of which 41 had methane production recorded on an ad libitum grain-based ration in the feedlot, 59 on a restricted grain-based ration in respiration chambers, and 57 on a restricted roughage ration in respiration chambers. The cattle became older and heavier as they went through the different phases of the experiment, but their feed intake (expressed as DMI) and daily emission of enteric methane (methane production rate; MPR) did not increase proportionally, as feed offered was restricted in the respiration chamber tests. Methane emissions by individual animals relative to their DMI were calculated as methane yield (MY; MPR/DMI) and as 2 measures of residual methane production (RMP and RMP), which were calculated as the difference between measured MPR and that predicted from feed intake by 2 different equations. Within each test regime, MPR was positively correlated ( = 0.28 to 0.61) with DMI. Phenotypic correlations for MY, RMP, and RMP between the feedlot test and the restricted grain test ( = 0.40 to 0.43) and between the restricted grain test and the restricted roughage test were moderate ( = 0.36 to 0.41) and moderate to strong between the feedlot test and the restricted roughage test ( = 0.54 to 0.58). These results indicate that the rankings of animals for methane production relative to feed consumed are relatively stable over the 3 test phases. Feedlot feed conversion ratio and RFI were not correlated with MPR in the feedlot test and grain-based chamber test but were negatively correlated with MPR in the chamber roughage test ( = -0.31 and -0.37). Both were negatively correlated with MY and RMP in the feedlot test ( = -0.42 to -0.54) and subsequent chamber roughage test ( = -0.27 to -0.49). Midparent estimated breeding values for RFI tended to be negatively correlated with MY and RMP in the feedlot test ( = -0.27 and -0.27) and were negatively correlated with MY, RMP, and RMP in the chamber roughage test ( = -0.33 to -0.36). These results showed that in young growing cattle, lower RFI was associated with higher MY, RMP, and RMP but had no significant association with MPR.

Genetic and phenotypic variance and covariance components for methane emission and postweaning traits in Angus cattle.

Ruminants contribute 80% of the global livestock greenhouse gas (GHG) emissions mainly through the production of methane, a byproduct of enteric microbial fermentation primarily in the rumen. Hence, reducing enteric methane production is essential in any GHG emissions reduction strategy in livestock. Data on 1,046 young bulls and heifers from 2 performance-recording research herds of Angus cattle were analyzed to provide genetic and phenotypic variance and covariance estimates for methane emissions and production traits and to examine the interrelationships among these traits. The cattle were fed a roughage diet at 1.2 times their estimated maintenance energy requirements and measured for methane production rate (MPR) in open circuit respiration chambers for 48 h. Traits studied included DMI during the methane measurement period, MPR, and methane yield (MY; MPR/DMI), with means of 6.1 kg/d (SD 1.3), 132 g/d (SD 25), and 22.0 g/kg (SD 2.3) DMI, respectively. Four forms of residual methane production (RMP), which is a measure of actual minus predicted MPR, were evaluated. For the first 3 forms, predicted MPR was calculated using published equations. For the fourth (RMP), predicted MPR was obtained by regression of MPR on DMI. Growth and body composition traits evaluated were birth weight (BWT), weaning weight (WWT), yearling weight (YWT), final weight (FWT), and ultrasound measures of eye muscle area, rump fat depth, rib fat depth, and intramuscular fat. Heritability estimates were moderate for MPR (0.27 [SE 0.07]), MY (0.22 [SE 0.06]), and the RMP traits (0.19 [SE 0.06] for each), indicating that genetic improvement to reduce methane emissions is possible. The RMP traits and MY were strongly genetically correlated with each other (0.99 ± 0.01). The genetic correlation of MPR with MY as well as with the RMP traits was moderate (0.32 to 0.63). The genetic correlation between MPR and the growth traits (except BWT) was strong (0.79 to 0.86). These results indicate that selection for lower MPR may have undesired effect on animal productivity. On the other hand, MY and the RMPR were either not genetically correlated or weakly correlated with BWT, YWT, and FWT (-0.06 to 0.23) and body composition traits (-0.18 to 0.18). Therefore, selection for lower MY or RMPR would lead to lower MPR without impacting animal productivity. Where the use of a ratio trait (e.g., MY) is not desirable, selection on any of the forms of RMP would be an alternative.

Genomic heritabilities and genomic estimated breeding values for methane traits in Angus cattle.

Enteric methane emissions from beef cattle are a significant component of total greenhouse gas emissions from agriculture. The variation between beef cattle in methane emissions is partly genetic, whether measured as methane production, methane yield (methane production/DMI), or residual methane production (observed methane production - expected methane production), with heritabilities ranging from 0.19 to 0.29. This suggests methane emissions could be reduced by selection. Given the high cost of measuring methane production from individual beef cattle, genomic selection is the most feasible approach to achieve this reduction in emissions. We derived genomic EBV (GEBV) for methane traits from a reference set of 747 Angus animals phenotyped for methane traits and genotyped for 630,000 SNP. The accuracy of GEBV was tested in a validation set of 273 Angus animals phenotyped for the same traits. Accuracies of GEBV ranged from 0.29 ± 0.06 for methane yield and 0.35 ± 0.06 for residual methane production. Selection on GEBV using the genomic prediction equations derived here could reduce emissions for Angus cattle by roughly 5% over 10 yr.

Prevalence of subclinical thyroid failure in insulin-dependent diabetes.

A study was made of the distribution of primary thyroid failure, indicated by a raised serum TSH concentration, in 605 (294 males and 311 females) insulin-dependent (type I) diabetics, aged 21-84 yr, not previously suspected of having thyroid disease. The prevalence of a raised serum TSH concentration in females of all ages (17%) was significantly greater (P less than 0.0005) than that in males (6.1%) and increased with increasing age at onset of diabetes (P less than 0.05) and age at time of study (P less than 0.001) in females but not in males. There was no significant difference in the duration of diabetes when comparing patients with normal and raised serum TSH concentrations. The prevalence of a raised TSH concentration in late-onset insulin-dependent diabetics was no greater in patients requiring insulin within 3 months of diagnosis of diabetes than in those exhibiting secondary sulfonylurea failure, who required insulin more than 3 months after diagnosis. In type I diabetes, the prevalence of subclinical primary thyroid failure is considerably greater than has previously been suspected, with female late-onset insulin-dependent diabetics being at the greatest risk.

A clinical profile of back pain and disability in patients with spinal osteoporosis.

This study investigated the pain and disability experienced by 85 consecutive postmenopausal Caucasian women, average age 64 years (range 50-82), with spinal osteoporosis, referred to a specialist bone clinic. Symptoms were related to the numbers and severity of vertebral deformities, and degree of kyphosis. Persistent back pain was experienced by 54 (63%) in the lumbar spine and 53 (62%) in the thoracic spine. The severity of thoracic but not lumbar back pain was significantly related by Kendall rank correlation to degree of kyphosis (R = 0.255, p < 0.01), numbers of collapsed vertebrae (R = 0.279, p < 0.01) and a summed score of the severity of collapse for all vertebrae (R = 0.253, p < 0.01). The severity and duration of thoracic back pain was also significantly related to numbers of collapsed vertebrae from T4-T8 alone. Sleep was disturbed in 60%, difficulty obtaining suitable clothes was found in 42% and difficulties with functional activities in 47%, although these were severe in only 10%. Significant associations were also found between scores of osteoporosis severity and sleep disturbance, difficulties with clothes and many functional activities. We conclude that in patients with spinal osteoporosis coming to medical attention, assessment and management of pain, disability, sleep pattern and difficulties with obtaining clothes are required for optimal care.

Insulin-like growth factor-I and bone mineral density.

To assess the relationship between insulin-like growth factor-I (IGF-I) and bone mineral density (BMD) 201 healthy postmenopausal women (age 41-68 years) within 10 years of menopause were studied. In all subjects, BMD at the lumbar spine and left hip were measured using dual-energy X-ray absorptiometry and blood samples were obtained. In all subjects, serum IGF-I and parathyroid hormone (PTH) were measured. In a subgroup of these subjects serum concentrations of IGF-binding protein-3 (IGFBP-3), osteocalcin (OC), bone-specific alkaline phosphatase (BALP), tartrate-resistant acid phosphatase (TRAP), and carboxyterminal propeptide of type I procollagen (PICP) were also measured. Serum IGF-I correlated significantly with age (r = -0.159, p = 0.0241), serum OC (r = 0.226, p = 0.0131), BALP (r = 0.259, p < 0.0001), and TRAP (r = 0.261, p < 0.0015), but not with PICP, PTH, or BMD at any site. Although there was a strong correlation between IGF-I and IGFBP-3 (r = 0.559, p < 0.0001), there was no correlation between IGFBP-3 and any of the markers of bone turnover (OC, BALP, TRAP, or PICP) nor with PTH or BMD at any site. We conclude that IGF-I and markers of bone turnover are related, but there is no relationship between IGF-I and BMD.

The prevention of early postmenopausal bone loss by cyclical etidronate therapy: a 2-year, double-blind, placebo-controlled study.

PURPOSE: To determine whether intermittent cyclical etidronate therapy can prevent early postmenopausal bone loss. PATIENTS AND METHOD: This was a 2-year outpatient, randomized, double-blind, placebo-controlled clinical trial. The subjects were 152 women within 1 to 10 years of the onset of menopause and bone mineral density (BMD) between 0 and -2 SD of normal values for a 50 year old woman. The women were stratified according to years since the menopause (1 to 3 years: n = 43; 4 to 6 years: n = 53; 7 to 10 years: n = 56). Measurements of lumbar spine, proximal femur and total body BMD were performed at baseline, 12 and 24 months by dual x-ray absorptiometry. Biochemical markers of bone resorption and bone formation were measured on the same visits. RESULTS: One hundred thirty-five subjects completed the study. Mean percentage change in lumbar spine BMD (and SEM) at 2 years was +2.14 (0.47)% in the etidronate group and -1.72 (0.41)% in the placebo group. Results for lumbar spine BMD in the treated and control groups stratified according to years since the menopause were: 1 to 3 years: +1.73 (0.84)% and -3.30 (0.70)%; 4 to 6 years: +1.37 (0.88)% and -1.80 (0.61)%; 7 to 10 years: +3.42 (0.61)% and -0.38 (0.70)%. The effect of both treatment group and menopausal stratum were highly statistically significant for lumbar spine and total body BMD. Treatment group, but not stratum, was significant for BMD in the proximal femur. Markers of bone resorption and bone formation were significantly decreased by etidronate therapy. CONCLUSIONS: Cyclical etidronate prevents bone loss in the total skeleton and at the clinically relevant sites (spine and proximal femur) even in the early postmenopausal years. Hence, it appears to be an effective and safe nonhormonal therapy in postmenopausal women with normal or low BMD.

Persistence of ivermectin in plasma and faeces following treatment of cows with ivermectin sustained-release, pour-on or injectable formulations.

Sixteen young dairy cows were randomly allocated to 4 groups of 4 animals each: Group 1 cows were each given a single Ivomec SR Bolus; Group 2 cows were treated with the Ivomec Pour-on formulation; Group 3 cows were injected with the Ivomec Subcutaneous Injection; Group 4 cows were untreated controls. Blood and faecal samples were collected from all cows on the day before treatment and on days 1, 2, 3, 7, 14, 21, 28, 35, 42 and 49 after treatment for HPLC determination of plasma and faecal ivermectin concentrations. Group 1 (SR Bolus) cows had mean (+/- S.D.) plasma ivermectin concentrations ranging from 5.6 +/- 1.8 micrograms l-1 (p.p.b.) at 14 days to 11.0 +/- 4.7 micrograms l-1 at 49 days. Faecal ivermectin concentrations were little changed from 4.0 +/- 2.0 micrograms g-1 (p.p.m.) dry wt (dry weight) [0.5 +/- 0.2 microgram g-1 wet wt (wet weight)] at 14 days to 3.0 +/- 2.0 micrograms g-1 dry wt (0.5 +/- 0.4 microgram g-1 wet wt) at 49 days. Group 2 (Pour-on) cows showed a rapid rise in plasma concentrations to 32.9 +/- 15.7 micrograms l-1 2 days after treatment, followed by a gradual decline to 1.3 +/- 0.07 micrograms l-1 at 28 days. Faecal ivermectin concentrations rose sharply to 18.5 +/- 7.4 micrograms g-1 dry wt (2.8 +/- 1.2 micrograms g-1 wet wt) 2 days after treatment, then fell to 0.04 +/- 0.004 microgram g-1 dry wt (0.006 +/- 0.0004 microgram g-1 wet wt) at 28 days. Group 3 (Injection) cows also showed a rapid rise to an early plasma peak of 46.1 +/- 22.7 micrograms l-1 3 days after treatment, followed by a gradual decline to 1.3 micrograms l-1 at 35 days. Faecal ivermectin concentrations rose to 1.2 +/- 0.34 micrograms g-1 dry wt (0.2 +/- 0.05 microgram g-1 wet wt) at 3 days, declining to 0.08 +/- 0.0001 microgram g-1 dry wt (0.01 +/- 0.0008 microgram g-1 wet wt) at 28 days. No ivermectin was detected in the plasma or faeces of Group 4 (Control) cows. Concentrations of ivermectin potentially toxic to dung-breeding or dung-feeding invertebrates were excreted for the duration of the study in dung of cows treated with the SR Bolus and for 28 days in the dung of cows treated with the Pour-on or injectable formulations.

Serum alpha 2-macroglobulin levels in diabetes.

Serum alpha 2-macroglobulin levels have been determined in diabetic patients by quantitative radial immunodiffusion and compared with those observed in age- and sex-matched controls. In addition, the results in diabetics have been analysed with respect to such variables as the age and sex of the patient, the duration of disease, treatment, control, and the occurrence of retinopathy or nephropathy. The alpha 2-macroglobulin levels in diabetic patients were found to be significantly higher than in age- and sex-matched controls, thus confirming previous observations. However, these differences were most apparent in the more extreme age groups. Multiple regression analysis also revealed that the only variables contributing significantly to the regression apart from age and sex were control and retinopathy.

Cardiac effects of sodium stibogluconate: myocardial, electrophysiological and biochemical studies.

The pentavalent antimonial sodium stibogluconate is the mainstay of anti-leishmanial therapy. Sodium stibogluconate is less cardiotoxic than antimony and the trivalent derivatives, but has been associated with dose-related electrocardiographic changes. The effect of the currently-used regimen of sodium stibogluconate (20 mg/kg/day for 20 days) on cardiac function is uncertain. We studied 12 soldiers, mean age 24 years, with proven cutaneous leishmaniasis treated with this regimen. There were no significant changes in echocardiographic indices of left ventricular systolic or diastolic function during treatment. Indices of myocardial electrical stability (heart-rate variability and episodes of overt supraventricular and ventricular arrhythmias) were unchanged, but there was a reversible decrease in T-wave amplitude during treatment. Systolic and diastolic blood pressure fell and the heart rate increased during treatment. This regimen of sodium stibogluconate does not measurably impair left ventricular systolic or diastolic function. Minor T-wave changes occur during treatment, but there is no increase in arrhythmia frequency or change in heart-rate variability. In most young fit patients, this regimen has no cardiac side-effects. However, idiosyncratic reactions cannot be excluded, and patients with malnutrition, impaired renal function or pre-existing heart disease may be more sensitive to any cardiotoxic properties of sodium stibogluconate.