Association between bovine digital dermatitis treponemes and a range of 'non-healing' bovine hoof disorders.

This study describes the association between bovine digital dermatitis (BDD) treponemes and three 'non-healing' bovine hoof horn lesions, namely, 'toe necrosis' (TN), 'non-healing white line disease' (nhWLD) and 'non-healing sole ulcer' (nhSU), which are disorders that involve penetration through the horn capsule to involve the corium. In this study, these non-healing disorders (n=44) were identified as foot lesions that exhibited a topical granular appearance, exuded a typical pungent smell, were severely painful to the animal involved, and typically originated from farms where BDD is endemic. Given the similarities between these 'non-healing' lesions and BDD, the authors subjected samples of diseased tissue to PCR assays to detect the presence of DNA of BDD treponemes. All the three characterised BDD treponeme groups were identified as present together in 84.2, 81.3 and 55.6 per cent of samples of TN (n=19), nhWLD (n=16) and nhSU (n=9), respectively. In contrast, healthy control horn samples from similar sites (n=16) were PCR-negative for the BDD treponemes. Hence, these non-healing hoof lesions were strongly associated with BDD treponemes. Samples from typical heel horn erosions (n=9) were also subjected to BDD treponeme PCR assays and no association could be identified between the BDD treponemes and this horn manifestation.

Thyroid function at diagnosis of type I diabetes.

BACKGROUND: National guidelines recommend that thyroid function is assessed at diagnosis of type I diabetes (TIDM) and annually thereafter. This paper reports an audit of thyroid surveillance in accordance with this guideline. PATIENTS: 110 patients (66 males), median age 11.3 (1.2-15.7) years at diagnosis of TIDM, were monitored for 2.3 (0.7-4.2) years. RESULTS: 21/110 (19.0%) patients had abnormal thyroid function at diagnosis of TIDM. Of these, 16 had normal thyroid function on reassessment after 45 (3-540) days. Abnormalities of thyroid function occurred more commonly in children with diabetic ketoacidosis (DKA) than those who did not have DKA (9/29, 31.0% vs 12/81, 14.8%, p<0.025). At the end of the observation period, five (4.5%) patients had minor abnormalities of thyroid function not requiring treatment and three (2.7%) were treated. CONCLUSIONS: Transient abnormalities of thyroid function are common at diagnosis of TIDM, and therefore, thyroid hormones should not be measured at this time.

Biochemical severity of thyroid ectopia in congenital hypothyroidism demonstrates sexual dimorphism.

BACKGROUND: A recent study suggested that sexual dimorphism affects initial thyroid function in congenital hypothyroidism (CH) but differs according to aetiology of CH. AIMS: To determine if sexual dimorphism was associated with biochemical severity of CH and its aetiology in our large British population. METHODS: We examined retrospectively the initial thyroid function tests of 140 infants diagnosed with CH from screening. All infants underwent Tc-pertechnetate radionuclide scans at diagnosis to establish the aetiology of CH prior to commencement of treatment. Patients were classified into athyreosis, ectopia and presumed dyshormonogenesis on the basis of thyroid scans. A comparison of males and females were made within the three aetiological groups for gestational age, birth weight, initial dose of levothyroxine (LT4), screening TSH, confirmatory plasma thyroxine (T4), confirmatory plasma TSH and age of TSH suppression. RESULTS: There was no significant difference between sexes for gestation, birth weight and initial treatment dose in all aetiological subgroups. In thyroid ectopia, screening TSH and confirmatory plasma TSH were significantly higher in females compared with males (P < 0.01), while confirmatory plasma T4 were significantly lower in females (P < 0.05). No difference was detected between males and females in athyreosis and dyshormonogenesis subgroups for screening TSH, confirmatory plasma TSH and total T4. CONCLUSION: Sexual dimorphism influenced the biochemical severity of thyroid ectopia in congenital hypothyroidism in our British population. However, this effect was not apparent in patients with athyreosis or dyshormonogenesis. Further advances in the molecular genetics of CH are essential to evaluate this phenomenon further.

Guanidinoacetate methyltransferase deficiency masquerading as a mitochondrial encephalopathy.

Guanidinoacetate methyltransferase (GAMT) deficiency is a rare disorder of creatine synthesis. We report a patient who presented at 10 months of age with hypotonia and global developmental delay. Subsequently, she developed seizures and choreoathetosis. Magnetic resonance imaging showed high signal bilaterally in the globus pallidus on T2-weighted images. Mitochondrial respiratory chain studies revealed low complex I activity (in muscle 0.052 nmol NADH oxidized per min per unit citrate synthase, controls 0.166 +/- 0.047; in fibroblasts 0.080 nmol NADH oxidized per min per unit citrate synthase, controls 0.197 +/- 0.034). The true diagnosis was suspected at 21 months of age because of persistent low plasma and urine creatinine concentrations. GAMT activity was undetectable in fibroblasts and compound heterozygous mutations were found in the GAMT gene (c.327G>A and c.522G>A). The patient was treated with creatine, dietary arginine restriction and ornithine supplements. Her movement disorder and seizures resolved but she still has severe cognitive impairment and no expressive language. The occurrence of secondary respiratory chain abnormalities in GAMT deficiency may lead to misdiagnosis, particularly as the clinical and radiological features resemble those seen in mitochondrial encephalopathies. It is important to establish the correct diagnosis because specific treatment is available.

Multivariate analysis on factors affecting suppression of thyroid-stimulating hormone in treated congenital hypothyroidism.

AIMS: To determine the factors which influence the suppression of thyroid-stimulating hormone (TSH) in infants with congenital hypothyroidism (CH) following treatment. METHODS: We examined retrospectively the patterns of thyroid function tests from diagnosis to 3 years of age in 140 infants diagnosed with CH from screening. Patients were classified into 3 groups: athyreosis, ectopia and presumed dyshormonogenesis on the basis of thyroid scans. Adequate TSH suppression was defined as plasma TSH concentration <6 mU/l. The factors affecting the suppression of TSH at 6 months and 1 year of age which were evaluated were: initial confirmatory plasma TSH, initial plasma thyroxine (T4), mean age of starting treatment with L-T4, dose of L-T4 at diagnosis, 6 weeks, 3 months and 6 months, and aetiology of the congenital hypothyroidism. Variables were then entered in a stepwise logistic regression model for TSH suppression at 6 months and 1 year of age. RESULTS: All infants had radionuclide scans prior to treatment: athyreosis (n = 39), ectopia (n = 78) and dyshormonogenesis (n = 23). 58% of patients had persistently raised TSH at 6 months of age while 31% of patients had a persistently raised TSH at 1 year of age. There was a significant delay in the normalisation of plasma TSH in athyreosis and ectopia groups compared with dyshormonogenesis. Multiple regression analysis for TSH suppression at 6 months of age found plasma T4 levels and aetiology of CH as independent factors affecting the timing of TSH suppression. Aetiology of CH was the only independent factor affecting TSH suppression at 1 year of age. CONCLUSION: At 6 months of age, plasma T4 levels at 6 weeks and 3 months, and aetiology of CH were independent factors affecting timing of TSH suppression. However, by 1 year of age, the aetiology of CH was the only independent factor affecting suppression of TSH.

Extensive interbreed, but minimal intrabreed, variation of DLA class II alleles and haplotypes in dogs.

The DLA class II genes in the dog major histocompatibility complex are highly polymorphic. To date, 52 DLA-DRB1, 16 DLA-DQA1 and 41 DLA-DQB1 allelic sequences have been assigned. The aim of this study was to examine the intrabreed and interbreed variation of DLA allele and haplotype frequencies in dogs, and to ascertain whether conserved DLA class II haplotypes occur within and between different breeds. One thousand and 25 DNA samples from over 80 different breeds were DLA class II genotyped, the number of dogs per breed ranging from 1 to 61. DNA sequence based typing and sequence specific oligonucleotide probing were used to characterize dogs for their DLA-DRB1, DQA1 and DQB1 alleles. The high frequency of DLA class II homozygous animals (35%), allowed the assignment of many haplotypes despite the absence of family data. Four new DLA alleles were identified during the course of this study. Analysis of the data revealed considerable interbreed variation, not only in allele frequency, but also in the numbers of alleles found per breed. There was also considerable variation in the number of breeds in which particular alleles were found. These interbreed variations were found in all three DLA class II loci tested, and also applied to the three-locus haplotypes identified. Within this data set, 58 different DLA-DRB1/DQA1/DQB1 three-locus haplotypes were identified, which were all found in at least two different animals. Some of the haplotypes appeared to be characteristic of certain breeds. The high interbreed, and relatively low intrabreed, variation of MHC alleles and haplotypes found in this study could provide an explanation for reports of interbreed variation of immune responses to vaccines, viruses and other infections.

Evidence of Bartonella henselae infection in cats and dogs in the United Kingdom.

Sera from cats and dogs in the UK were tested by ELISA for antibodies to Bartonella henselae. Seropositivity was confirmed in 28 of 69 pet cats (40.6 per cent), 33 of 79 feral cats (41.8 per cent) and three of 100 pet dogs. Reactivity to specific B. henselae antigens was confirmed by Western blotting and demonstrated that consistent antigenic bands were bound by sera from the cats and dogs.

Development and progression of microalbuminuria in a clinic sample of patients with insulin dependent diabetes mellitus.

The evolution of abnormal albumin excretion and its association with suggested risk factors were studied in 233 children with insulin dependent diabetes mellitus (IDDM) attending a single paediatric diabetic clinic over an eight year period. Yearly albumin:creatinine ratios (ACR; measured in mg/mmol) in early morning urine samples, glycated haemoglobin (HbA1c), and blood pressure were recorded. Thirty four (14.5%) children had a persistently raised ACR (ACR > or = 2.5 mg/mmol on at least three consecutive occasions) and 21 (9%) had an intermittently raised ACR (ACR > or = 2.5 mg/mmol on at least two occasions). Factors associated with a persistently raised ACR compared with normal albuminuria in IDDM included longer duration of diabetes, raised median HbA1c during the first five years after diagnosis, and final age adjusted systolic and diastolic blood pressure represented as standard deviation scores. The onset of persistently raised ACR in 13 of 34 children was before puberty and in 23 of 34 children it was within the first four years of diagnosis. The cross sectional prevalence of raised ACR was 12.9% at one year, 18.3% at five years, and 33% at 10 years after diagnosis. Raised ACR occurs frequently before puberty and in the early stages of childhood diabetes.

Hypoalbuminaemia in surgical neonates receiving parenteral nutrition.

The aim of this study was to define the prevalence of hypoalbuminaemia (HA), its predisposing factors, and its effect on outcome in infants. Fifty-six consecutive infants receiving parenteral nutrition (PN) for gastrointestinal disease were divided into two groups according to their lowest measured serum albumin level. The reference range (27.9 to 50.9 g/L) for serum albumin was derived from measurements taken in 37 (22 term and 15 preterm) normal enterally fed newborn infants. HA group (serum albumin < 27.9 g/L) included 15 infants (27%); NA group (serum albumin > or = 27.9 g/L) included 41 infants (73%). HA infants received more albumin than NA infants (median 66 versus 14 mL/kg; P = .005). There was no significant difference between HA and NA groups in gestational age, postmenstrual age at time of start of PN, composition of PN, nor mean weight gain. HA was unrelated to biochemical signs of liver dysfunction, C-reactive protein elevation, septicaemic episodes, or time from operation. HA occurred within the first week of starting PN in 10 infants and returned to normal values within 5 days. HA was a recurrent phenomenon in three patients. Mortality was higher in the HA group (33.3%) than in the NA group (4.9%; P = .02) but was apparently causally unrelated to the low serum albumin level. Hypoalbuminaemia is a common finding in neonates on PN despite the administration of exogenous albumin. Monitoring serum albumin levels in surgical infants on PN seems to be of little clinical value.

Autoimmune Addison's disease and thyrotoxic thyroiditis presenting as encephalopathy in twins.

An 11 year old boy who presented with neuropsychiatric symptoms including delirium and pronounced agitation was found to have simultaneous onset of autoimmune adrenocortical insufficiency and hyperthyroidism. His identical twin also had hyperthyroidism and six months later developed symptoms of adrenocortical insufficiency. In children presenting with neuropsychiatric symptoms, adrenal (or pituitary) and other endocrine disorders should be considered.

Glycosylated haemoglobin and glucose intolerance in cystic fibrosis.

Sixty four patients, age range 1-20 years, with cystic fibrosis had their tolerance to glucose assessed according to their glycosylated haemoglobin (HbA1) concentrations. Raised concentrations were found in 24 (37.5%). Oral glucose tolerance tests were performed on 21 patients with raised HbA1 and 13 patients with normal HbA1 concentrations. C peptide responses were also measured to assess islet cell function. Patients with normal HbA1 had normal glucose tolerance and C peptide response. Seven of 21 patients with raised HbA1 concentrations were glucose intolerant. The remaining 14 patients with raised HbA1 concentrations had normal glucose tolerance but a reduced C peptide response, suggesting impaired islet cell function. There were no appreciable differences in the incidence of chest infections, respiratory function, and chest x-ray scores among patients with normal HbA1 concentrations, raised HbA1 concentrations, and normal oral glucose tolerant tests, and patients who were glucose intolerant. No correlation was found between HbA1 concentration and age or Shwachman score. Measuring HbA1 concentrations periodically is useful in detecting and monitoring glucose intolerance in patients with cystic fibrosis.