Temporal artery biopsies in south-east Scotland: a five year review.

Temporal artery biopsy is the gold standard investigation for the diagnosis of giant cell arteritis. The aim of this retrospective study was to investigate the use of temporal artery biopsy in diagnosing giant cell arteritis in south-east Scotland over a five-year period. We aimed to quantify success rates, and predictive factors for a positive biopsy, as well as compare the different specialities performing the biopsies. The data should enable the development of better criteria for referral for investigation of giant cell arteritis. Methods Patients were identified using a database of temporal artery biopsies generated by the pathology department in NHS Lothian (south east Scotland), for all biopsies examined between January 2010 and December 2015. An electronic patient record was used to retrospectively examine the records of patients in the database. Results A total of 715 biopsies were included in the study, of which 250 (35.0%) showed features of giant cell arteritis. The main predictors for a positive biopsy were age at biopsy, specialty performing biopsy, erythrocyte sedimentation rate, jaw claudication/pain, and ophthalmic symptoms. The most important predictor of a positive biopsy was erythrocyte sedimentation rate. The length of biopsy was not found to be a predictor of positive biopsy; however, diameter of biopsy was predictive. Conclusions We have shown that many temporal artery biopsies are negative, and finding ways to reduce the number of patients unnecessarily undergoing biopsy will be essential in reducing workload and streamlining services. This study demonstrates some key predictive factors for patients with positive biopsies. The study also shows that a large proportion of biopsies taking place do not result in the recommended length of specimen, but this does not necessarily reduce the likelihood of a positive biopsy.

The accuracy of the Edinburgh visual loss diagnostic algorithm.

PURPOSE: To assess the diagnostic accuracy of the Edinburgh visual loss algorithm. METHODS: This was a prospective study. Patients referred to the Edinburgh Eye Pavilion with visual loss were assessed using the Edinburgh Visual Loss Algorithm by either a medical student, an inexperienced ophthalmology trainee or an optometrist in the Lothian Optometry Treat and Teach clinic. Accuracy of this 'algorithm-assisted' diagnosis was then compared with the 'gold-standard' diagnosis, made by an experienced ophthalmologist. Accuracy of the pre-algorithm diagnosis, made by the referrer, was also compared with the algorithm-assisted diagnosis. RESULTS: All patients referred with visual loss were eligible for inclusion. Seventy patients were assessed; two were excluded. Pre-algorithm accuracy of referral of patients with visual loss was 51% (30/59). Overall, the algorithm-assisted diagnosis was correct 84% (57/68) of the time. The algorithm correctly diagnosed: retina in 71% of cases (5/7), macula in 86% (25/29), peripheral retina in 100% (2/2), optic nerve in 71% (5/7), media opacity in 89% (16/18), post chiasmal in 100% (4/4), and refractive error in 0% (0/1). Accuracy of diagnosis was similar for each algorithm user; medical student 81%, inexperienced ophthalmology trainee 84% and optometrist 92%. DISCUSSION: The baseline diagnostic accuracy of clinicians who are inexperienced in ophthalmology rose from 51 to 84% when patients were assessed using the algorithm. This algorithm significantly improves the diagnostic accuracy of referrals to the hospital eye service, regardless of the user's previous ophthalmic experience. We hope we have demonstrated its potential as a learning tool for inexperienced clinicians.

Analysis of Short-Term Cortisol Stress Response in Channel Catfish by Anesthetization with Metomidate Hydrochloride and Tricaine Methanesulfonate.

The ability of the anesthetics metomidate hydrochloride and tricaine methanesulfonate (MS-222) to mitigate the cortisol stress response of Channel Catfish Ictalurus punctatus was evaluated during a 10-min confinement stress. The cortisol concentrations of Channel Catfish anesthetized in metomidate hydrochloride remained consistent throughout the 10-min exposure; however, for fish anesthetized with MS-222 and nonanesthetized fish, cortisol concentrations were approximately 7- and 22-fold higher, respectively, than the baseline concentrations. While both anesthetics reduced cortisol concentrations relative to those of nonanesthetized fish, these results suggest that MS-222 is an appropriate anesthetic to use during the initial 5 min of sedation and that metomidate hydrochloride is appropriate for longer periods of sedation.

Somatic CALR mutations in myeloproliferative neoplasms with nonmutated JAK2.

BACKGROUND: Somatic mutations in the Janus kinase 2 gene (JAK2) occur in many myeloproliferative neoplasms, but the molecular pathogenesis of myeloproliferative neoplasms with nonmutated JAK2 is obscure, and the diagnosis of these neoplasms remains a challenge. METHODS: We performed exome sequencing of samples obtained from 151 patients with myeloproliferative neoplasms. The mutation status of the gene encoding calreticulin (CALR) was assessed in an additional 1345 hematologic cancers, 1517 other cancers, and 550 controls. We established phylogenetic trees using hematopoietic colonies. We assessed calreticulin subcellular localization using immunofluorescence and flow cytometry. RESULTS: Exome sequencing identified 1498 mutations in 151 patients, with medians of 6.5, 6.5, and 13.0 mutations per patient in samples of polycythemia vera, essential thrombocythemia, and myelofibrosis, respectively. Somatic CALR mutations were found in 70 to 84% of samples of myeloproliferative neoplasms with nonmutated JAK2, in 8% of myelodysplasia samples, in occasional samples of other myeloid cancers, and in none of the other cancers. A total of 148 CALR mutations were identified with 19 distinct variants. Mutations were located in exon 9 and generated a +1 base-pair frameshift, which would result in a mutant protein with a novel C-terminal. Mutant calreticulin was observed in the endoplasmic reticulum without increased cell-surface or Golgi accumulation. Patients with myeloproliferative neoplasms carrying CALR mutations presented with higher platelet counts and lower hemoglobin levels than patients with mutated JAK2. Mutation of CALR was detected in hematopoietic stem and progenitor cells. Clonal analyses showed CALR mutations in the earliest phylogenetic node, a finding consistent with its role as an initiating mutation in some patients. CONCLUSIONS: Somatic mutations in the endoplasmic reticulum chaperone CALR were found in a majority of patients with myeloproliferative neoplasms with nonmutated JAK2. (Funded by the Kay Kendall Leukaemia Fund and others.).

Sex-linkage of glucosephosphate isomerase-B and mapping of the sex-determining gene in channel catfish.

Sex-linkage of glucosephosphate isomerase-B (GPI-B) was observed in five experimental matings between heterozygous male and homozygous female channel catfish (Ictalurus punctatus). Offspring phenotypes for GPI-B were 40.8% heterozygous male and 43.0% homozygous female, while recombinant offspring were 7.4% homozygous male and 8.8% heterozygous female. Thus, GPI-B and the sex-determining gene (SDG) were linked and had a recombination rate of 16.2%. This linkage was designated I. punctatus linkage group XXIX. The gene-centromere distance (1.66 cM) of SDG, estimated in six gynogenetic families derived from XY females, indicated that SDG resides very close to the centromere. Based on estimates of these genetic distances, a chromosomal order of GPI-B-centromere-SDG was proposed. Additionally, joint segregation of GPI-A and SDG in two experimental matings indicated no genetic linkage between GPI-A and sex. These genetic relationships were compared to those reported in other teleost taxa with regard to evolutionary conservation of ancestral gene arrangements.

Influence of dihydrotestosterone on sex determination in channel catfish and blue catfish: period of developmental sensitivity.

Treatment of channel catfish with 0.2, 20, or 200 mg/liter of dihydrotestosterone (DHT) in the water during the egg stage or during egg and sac-fry stages did not alter the expected 1:1 sex ratio of the progeny. Feeding DHT at 200 mg/kg of feed for the first 21 days after yolk sac absorption resulted in 80% females; this proportion was increased by combining feeding with treatment of 200 mg DHT/liter in the sac-fry stage (90%) or in the egg and sac-fry stage (97%). In contrast, treatment of blue catfish sac-fry with 200 mg DHT/liter, with or without the combination of feeding DHT at 200 mg/kg food, resulted in 100% female populations. Neither clomiphene citrate, an estrogen-receptor blocking agent, nor clofibrate, an inhibitor of hepatic synthesis of cholesterol, affected the sex ratio of channel catfish, and neither of these compounds altered the feminizing effect of 200 mg DHT/kg when fed in combination with DHT. The nonaromatizable androgen DHT is not as effective as many other androgens in producing paradoxical female populations of channel catfish. However, feminization of blue catfish by treatment of sac-fry indicates that this species is more susceptible to hormonal manipulation and that the period of sex determination may occur earlier in development than in channel catfish.

Hormonal sex manipulation and evidence for female homogamety in channel catfish.

The mechanism of sex determination in channel catfish Ictalurus punctatus was evaluated by hormonal and genetic methods. Aromatizable and nonaromatizable androgens, as well as an estrogen, caused feminization in fish fed steroids for 21 days after yolk-sac absorption. The effectiveness of 60 micrograms of ethynyltestosterone/g food decreased markedly when the experimental feeding period was shortened and was ineffective when the treatment lasted less than 12 days. Females from all-female populations produced by treatment with sex hormones were mated with normal males resulting in nine spawns with a sex ratio different from 1:1. The sex ratios were statistically similar to 3 male: 1 female in five spawns, both 2:1 and 3:1 in two spawns, and 2:1 in two spawns. These data are consistent with a model for female homogametic sex determination in channel catfish and suggest that the YY equivalent genotype is viable.

Extraction of a synthetic androgen from fish muscle and quantitation by high performance liquid chromatography.

A rapid, reproducible extraction procedure was developed to recover the synthetic androgen 17 alpha-methyltestosterone (MT) from fish muscle. A single extraction with chloroform-methanol (2:1 V/V), followed by elution from mini-columns with various methanol concentrations, yielded an extraction efficiency of greater than 70%. Resolution of MT from testosterone was complete and reliable quantitation was achieved utilizing reversed-phase high performance liquid chromatography. Endogenous testosterone was not detectable in 1-g muscle samples, but MT was detected in fish muscle 6 h after adult Tilapia aurea were fed a diet containing the steroid.

Selenium: relation to decreased toxicity of methylmercury added to diets containing tuna.

Japanese quail given 20 parts per million of mercury as methylmercury in diets containing 17 percent (by weight) tuna survived longer than quail given this concentration of methylmercury in a corn-soya diet. Tuna has a relatively high content of selenium and tends to accumulate additional selenium when mercury is present. A content of selenium in the diet comparable to that supplied by tuna decreased methylmercury toxicity in rats. Selenium in tuna, far from being a hazard in itself, may lessen the danger to man of mercury in tuna.