Improving surveillance of sexually transmitted infections using mandatory electronic clinical reporting: the genitourinary medicine clinic activity dataset, England, 2009 to 2013.

A new electronic surveillance system for sexually transmitted infections (STIs) was introduced in England in 2009. The genitourinary medicine clinic activity dataset (GUMCAD) is a mandatory, disaggregated, pseudo-anonymised data return submitted by all STI clinics across England. The dataset includes information on all STI diagnoses made and services provided alongside demographic characteristics for every patient attendance at a clinic. The new system enables the timely analysis and publication of routine STI data, detailed analyses of risk groups and longitudinal analyses of clinic attendees. The system offers flexibility so new codes can be introduced to help monitor outbreaks or unusual STI activity. From January 2009 to December 2013 inclusive, over twenty-five million records from a total of 6,668,648 patients of STI clinics have been submitted. This article describes the successful implementation of this new surveillance system and the types of epidemiological outputs and analyses that GUMCAD enables. The challenges faced are discussed and forthcoming developments in STI surveillance in England are described.

Rapid increase in gonorrhoea and syphilis diagnoses in England in 2011.

There has been a rapid rise in the number of gonorrhoea and syphilis diagnoses in England during 2011, an increase of 25% and 10% respectively. Large increases of both gonorrhoea (61%) and syphilis (28%) were observed among men who have sex with men. Although these rises can partly be attributed to increased testing, ongoing high-levels of unsafe sexual behaviour probably contributed to the rise. The rise in gonorrhoea rates is worrying in an era of decreased susceptibility to treatments.

Development of chronic tests for endocrine active chemicals. Part 1. An extended fish early-life stage test for oestrogenic active chemicals in the fathead minnow (Pimephales promelas).

An extended early-life stage test (based on OECD test guideline 210) was developed to allow the evaluation of a weak environmental oestrogen, 4-tert-pentyphenol (4TPP), on sexual differentiation and gonadal development. Fathead minnow (Pimephales promelas) embryos were exposed to three concentrations of 4TPP (56, 180 and 560 microg l(-1)) in a flow-through system, at 25+/-1 degrees C, for <107 days post-hatch (dph). In addition, some embryos were exposed to 180 microg 4TPPl(-1) until 30 or 60 dph, after which they were exposed to dilution water only until 107 dph. At 30, 60 and 107 dph fish were evaluated for growth and gonadal development (via histology), and at 107 dph fish were also evaluated for secondary sexual characteristics (SSC), gonadosomatic index (GSI) and plasma vitellogenin (VTG). There were no effects of 4TPP on hatching success or survival, however, there was a delay in the time taken for embryos to hatch (560 microg 4TPPl(-1)). No treatment-related effects were observed on fish growth, with the exception of at 107 dph when the condition factor in female fish was reduced in all 4TPP continuous exposure treatments. Plasma VTG was only elevated in female fish exposed to 180 microg 4TPPl(-1) and inhibition of gonadal growth (GSI) occurred only in females exposed to 560 microg 4TPPl(-1). Histological examination of the gonads revealed delays and disruption in male sexual differentiation and development (180 microg 4TPPl(-1)) and no testicular tissue was observed in any fish exposed to 560 microg 4TPPl(-1). Mixed gonads (predominately testes with a scattering of primary oocytes) were present in fish exposed to all doses of 180 microg 4TPPl(-1) at 107 dph. Feminisation of the reproductive ducts (formation of an ovarian like cavity) occurred in the testis of all males exposed to 180 microg l(-1), regardless of length of 4TPP exposure. Results indicate that the period of 30-60 dph appears to be the sensitive window for disruption of formation of the reproductive duct and this effect is not reversible when the fish are transferred to dilution water. The data also show that this integrative test is suitable for the detection of a weak environmental oestrogen and comparisons of these results with that of a fish full life-cycle, in medaka, indicate that this test could be a suitable surrogate for a fish full life-cycle.

2-Halopropionic acid-induced cerebellar granule cell necrosis in the rat: in vivo and in vitro studies.

Daily oral administration of 2.3 mmol/kg L-2-chloropropionic acid (L-2-CPA), DL-2-bromopropionic acid (2-BPA) or DL-2-iodopropionic acid (2-/PA) but not DL-2-fluoropropionic acid (2-FPA) produced cerebellar granule cell necrosis in the rat. Twenty four hours after three doses of L-2-CPA or two doses of 2-BPA, animals showed clinical signs of motor incoordination and reduced hindlimb function which was associated with marked cerebellar oedema and cerebellar granule cell necrosis. Biochemical analyses showed a marked increase in cerebellar water and Na+ content, and a reduction in cerebellar glutamate and aspartate. 2-IPA at this dose was toxic, the animals not surviving a second dose, histopathology showed hepatic and renal necrosis with mild cerebellar granule cell necrosis. 2-FPA was not neurotoxic after four daily doses. A marked decrease in hepatic and cerebellar non-protein sulphydryl (NP-SH) content was observed 4 h after a single dose of 2.3 mmol/kg L-2-CPA, 2-BPA and 2-IPA but not 2-FPA. Daily doses of 2-BPA for 3 days produced a sustained 50% depletion in cerebellar NP-SH. In vitro, L-2-CPA, 2-BPA and 2-IPA produced glutathione (GSH) depletion in the presence of rat liver cytosol, while 2-FPA did not. Depletion of GSH in the presence of cerebellar cytosol was only observed with 2-IPA. Studies using primary cultures of rat cerebellar granule cells, showed that all analogues produced a concentration dependent loss of cell viability. Mean EC50 values for 2-FPA, L-2-CPA, 2-BPA and 2-IPA toxicity were 1.7, >10, 0.5 and 0.3 mM, respectively, for 24 h continuous exposure. MK-801 and Vitamin E afforded protection against L-2-CPA-induced cytotoxicity but not against the other analogues. In summary, in addition to L-2-CPA, both 2-BPA and 2-IPA produce cerebellar granule cell necrosis in the rat. Depletion of GSH in the cerebellum may be contributory factor in the cascade of events leading to neurotoxicity.

The effect of postnatal age on L-2-chloropropionic acid-induced cerebellar granule cell necrosis in the rat.

L-2-Chloropropionic acid (L-2-CPA) selectively damages the cerebellum in adult rats. The rat cerebellum continues to develop postnatally during the first 4 weeks of life. In this study we examined the neurotoxic effect on rats of increasing postnatal age. Daily oral dosing of rats aged 56 days with 250 mg/kg per day of L-2-CPA for 3 days produced necrosis to neurons in the cerebellar granule cell layer and to neurons in the medial/ventral region of the habenular nucleus. Rats aged 22 days were resistant to the cerebellar toxicity while rats aged 32 days and older were sensitive. A single large oral dose of 500 or 750 mg/kg L-2-CPA produced no clinical signs of neurotoxicity or lesions in the cerebellum 48 h after dosing in 22-day-old rats. Daily dosing of 22-day-old rats at 250 mg/kg per day L-2-CPA for 10 days also produced no signs of neurotoxicity or reduction in body weight gain, although histological examination of the brain revealed slight neuronal cell necrosis in the granule cell layer of the cerebellum with a minimal effect in the medial/ventral region of the habenular nucleus. In contrast, daily dosing of rats aged 32, 38, 48 and 58 days with 250 mg/kg per day of L-2-CPA for 3 days produced clear signs of neurotoxicity which were associated with reduced body weight gain and loss of hindlimb function. In these rats there was clear evidence of neuronal cell loss in the cerebellar granule cell layer and medial/ventral region of the habenular nucleus. This study showed that the postnatal developing cerebellum is resistant to L-CPA-induced injury in rats up to 25 days of age, but becomes vulnerable to the toxicity by 32 days of age. The basis for the resistance of the developing cerebellum to L-CPA is discussed.

The absence of cerebellar granule cell necrosis in the mouse following L-2-chloropropionic acid administration.

Oral administration of L-2-chloropropionic acid (L-CPA) to rats either as a single dose (750 mg/kg) or daily doses (250 mg/kg per day for 3 days) produces selective necrosis to the granule cell layer of the cerebellum. As part of a study to understand the mechanism of this selective toxicity, we investigated the toxicity of L-CPA and a related analogue, DL-2-bromopropionic acid to the mouse with particular emphasis on the brain. Following a single oral dose (up to 1000 mg/kg), or daily oral doses of 250 mg/kg per day L-CPA up to maximum tolerated doses, produced no evidence of neurotoxicity. Similarly, daily oral doses of DL-2-bromopropionic acid at 250 mg/kg per day produced no evidence of neurotoxicity. The basis for the lack of response was explored by examining the metabolism and disposition of L-[2-14C]-CPA in the mouse. Following a single oral dose of 250 mg/kg L-CPA, radioactivity was rapidly absorbed from the gastrointestinal tract into the blood stream. Peak plasma concentrations of radiolabel and L-CPA occurred within 2 h of dosing at about 1.8 mM, and were then lost from the plasma with a half-life of 1 h. The only metabolite detected in the plasma was 2-S-cysteinylpropanoic acid derived from the glutathione conjugate. About 39% of the dose was excreted in the urine in the first 24 h, mainly as 2-S-cysteinylpropanoic acid with only a small amount of unchanged L-CPA. The remaining radiolabel from L-CPA was excreted in the faeces (26%) and exhaled as carbon dioxide (about 14%) over 72 h. Radiolabel from L-[2-14C]-CPA was present in the cerebellum at a peak concentration of 1 mM 1-2 h after dosing and then was lost more slowly than from the plasma. Measurement of non-protein sulphydryl content in the brain, liver and kidneys showed a decrease in the liver and kidneys 4 h after dosing which recovered fairly rapidly, while a more prolonged decrease was found in the brain, especially the cerebellum. Our studies show that the mouse is refractory to cerebellar injury following treatment with L-CPA and DL-2-bromopropionic acid. The mouse appears to metabolize and excrete L-CPA as its glutathione-derived conjugate(s) more rapidly than the rat, thereby limiting the availability of L-CPA to the cerebellum, which may account for the absence of neuronal cell injury.

Morphometric analysis of the developing rat brain.

In 2 studies, a method of linear morphometry was applied to regulatory developmental neurotoxicity studies in the rat. The first study involved the development of the brain during postnatal days (PNDs) 7-63, and the second involved the effects of 8 mg/kg i.p. trimethyltin chloride (TMT) to rats at PND 8, with morphometry performed at PNDs 12 and 24. The results of the TMT linear morphometry were compared with those from stereologic counting of neurons in the cerebral cortex, piriform cortex, and hippocampus. Stereology produces more meaningful data than simple linear morphometry for use in the regulatory assessment of the developmental neurotoxicity potential of compounds.

Neuroprotection afforded by MK-801 against L-2-chloropropionic acid-induced cerebellar granule cell necrosis in the rat.

Administration of a single oral dose of 750 mg/kg L-2-chloropropionic acid (L-CPA) to rats produces marked necrosis to the granule cell layer of the cerebellum by 48 h after dosing. Associated with the neuropathology the rats show locomotor impairment and a loss of body weight and a significant increase in cerebellar water and sodium content, indicating an oedematous reaction. Cerebellar aspartate and glutamate concentrations were reduced, while glycine and glutamine concentrations were increased after this treatment. Administration of the N-methyl-D-aspartate (NMDA) receptor channel antagonist (5R,10S)-(+)-5-methyl-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5,1 0-imine (MK-801), 30 min prior to L-CPA at a dose of 0.5, 1 or 5 mg/kg i.p. prevented the necrosis to the granule cell layer of the cerebellum and the signs of motor incoordination. Similarly there was no loss in cerebellar aspartate or glutamate concentration or increase in water or sodium content. Prior treatment with MK-801 at 0.1 mg/kg did not afford protection against the neurotoxicity. Post-treatment with 1 mg/kg MK-801 up to 1 h after administering L-CPA afforded complete neuroprotection, however if delayed until 2 or 6 h it gave only partial protection, and after 12 h it gave no protection. Administration of MK-801 alone at 5 mg/kg i.p., did not alter water content, sodium concentration, aspartate or glutamate concentrations in the cerebellum. In conclusion, we have shown that MK-801 given prior to and 1 h after L-CPA can afford complete neuroprotection, suggesting that a sub-population of NMDA receptors located on granule cells in cerebellum play a key role in mediating the selective toxicity of this chemical to the rat cerebellum.

Spastic syndrome in a Holstein bull: a histologic study.

A 4-year-old Canadian holstein bull developed the spastic syndrome, an episodic but progressive disorder causing pelvic limb muscular spasms. A post-mortem study, including morphometry of skeletal muscles and teased peripheral nerve fibers of the pelvic limb, revealed mild type II skeletal muscle fiber atrophy and minimal, focal segmental demyelination with remyelination, and axonal degeneration in peripheral nerves. Such alterations are probably incidental or age-associated. Idiopathic muscular cramps is the most probable explanation of the clinical disease and is consistent with the absence of significant morphologic pathologic lesions.

Experimental microcyst sarcocystis infection in lambs: pathology.

Six 34- to 42-day-old lambs raised in coccidia-free conditions were inoculated with 70,000 sporocysts derived from sheep heart with microscopic sarcocysts. Fever and mild anorexia occurred between 25 and 33 days after inoculation. A transient anaemia was most marked 32 days after inoculation. Lambs were killed and examined 14, 25, 33, 42, 60 and 81 days after inoculation. Gross lesions were absent. First and second generation meronts were present in endothelial cells at 25 and 33 days after inoculation. Meronts were most numerous in kidney glomeruli. Developing sarcocysts were rare at 42 days after inoculation. Sarcocysts with a primary cyst wall 2 to 3 micron thick composed of palisade projections were common at 60 and 81 days after inoculation in striated muscle and brain. Mild to severe striated muscle myositis and non-suppurative encephalitis or encephalomyelitis with glial nodules were observed 25 to 81 days after inoculation. Sarcocyst frequency varied considerably; it was highest in myocardium, M vastus intermedius, M vastus medialis, M extensor carpi radialis and tongue muscle and was lowest in M masseter.

'Kangaroo gait' in ewes: a peripheral neuropathy.

The clinical and pathological features of two lactating ewes with 'kangaroo gait', a locomotory disorder, are described, along with brief details of two further archival cases. Clinical neuropathological signs were consistent with a bilateral radial paresis and pathologically there was a polyneuropathy with preferential severe involvement of radial nerves. Flock incidence of the condition is low and previous experience suggests the clinical disorder is not progressive, recovery occurring at the end of lactation. The cause is unknown.

Neuraxial oedema of Hereford calves with and without hypomyelinogenesis.

The clinical and pathological features of 11 Hereford calves with neuraxial oedema with and without hypomyelinogenesis are described. Calves were affected at birth, recumbent and showed intermittent extensor spasm and hyperaesthesia. Nystagmus was noted in six cases. Pathologically, vacuolation of the central nervous system was seen in all cases. In two calves of horned Hereford stock this was restricted to white matter areas, while in the remaining calves of polled Hereford origin it was distributed in both white and grey matter. Hypomyelinogenesis was also a feature of this latter group of calves.

Skeletal abnormality of sheep: clinical radiological and pathological account of occurrence of dwarf lambs.

Details are given of the clinical, radiological and pathological appearance of dwarf lambs. Twenty-seven of 110 lambs born were affected, occurring as singletons, twins or one of a pair of twins. All affected lambs were dead within a few minutes of birth. They were short and plump with a domed head and shortened nose, short paddle-like limbs, a narrow thorax and swollen abdomen. The defect involved chondrocyte dysplasia, producing defective endochondral ossification and the presence of abnormal cartilage in the respiratory tract. No specific genetic or environmental cause was identified.

Bovine virus diarrhoea-mucosal disease virus-induced fetopathy in cattle: Efficacy of prophylactic maternal pre-exposure.

Maternal immunity was produced in Jersey heifers by exposing them to bovine virus diarrhoea-mucosal disease virus before conception. In the following pregnancy this immunity protected the fetuses from transplacental infection arising from challenge of the dams at 100 days gestation with homologous virus. Unprotected Jersey heifers showed a high incidence of death and fetal intrauterine growth retardation associated with transplacental viral infection. Functional normality of the locomotor system was assessed retrospectively from ciné films of each calf after birth, and scored for each of an overlapping series of clinical signs. The progeny of non-immune dams scored significantly lower than calves from the vaccinated heifers.