The economic implications of unsuspected findings from CT urography performed for haematuria.

OBJECTIVES: We set out to determine the prevalence of unsuspected findings from CT urography (CTU) performed for haematuria and to evaluate the economic implications associated with the subsequent management of these findings. METHODS: We analysed the results of 778 consecutive CTU scans performed in a haematuria clinic between 2008 and 2010. We excluded cases where diagnosis of an abnormality had been made prior to CTU. Costs incurred during the follow-up of unsuspected findings were calculated following guidance set out in the NHS Costing Manual 2009/10. RESULTS: 778 CTU scans were performed for patients attending a haematuria clinic from 2008 to 2010. 455 men and 323 women underwent CTU scan; they had a median age of 62 years. 56% of scans were found to have unexpected extra-urinary findings (587 abnormalities in 439 scans). Common findings included diverticular disease (138, 17.7%), adrenal masses [85, 10.9%; 40 (5.1%) of which were indeterminate], lung abnormalities (67, 8.6%), gall bladders containing calculi (44, 5.7%), adnexal cysts (25, 7.7% of women) and aortic aneurysms (18, 2.3%). These findings led to a total of 136 outpatient appointments, 88 radiological investigations and 11 procedures (4 of which were major). The overall cost incurred was £47,366, or £60 per patient. CONCLUSION: CTU is associated with a high rate of unsuspected findings. There is an economic implication to performing CT scanning in this setting, in which further unanticipated investigation and treatment cost is approximately £60 per patient.

Quality and quantity: an audit of urodynamics practice in relation to newly published National Standards.

OBJECTIVE: To document urodynamic practice in Wales in relation to newly released National Minimum Standards with a view to influencing organisational change. METHODS: Three questionnaires, evaluating respectively, departmental practice, individual practice and the last 10 studies performed in that department, were sent to all departments performing urodynamics in Wales. Results 19/20 departments responded. Approximately 4,000 studies are performed annually in Wales. Three departments do not perform enough studies annually to meet minimum standards. The minimum standard of 30 studies annually is not met by most centers evaluating neuropathic patients or performing ambulatory tests. Eighty four percent of departments have a clinical lead, one quarter discuss urodynamics in the context of a multi-disciplinary team meeting and occasional audits are performed. Fifty-four staff perform urodynamics, of which 35 (65%) have attended a course. Ability to describe zeroing a transducer was scored out of 6 and respondents scored a median of 3/6. One hundred twenty two out of 168 (72%) of the studies audited asked a clear urodynamics question, but, in 22/168 (13%) this question was not answered. The urodynamics report was written immediately 85% of the time. CONCLUSION: Centers failing to meet the minimum standards for workload should consider their position in relation to standards and NICE guidance (UKCS, NICE). In particular, departments should give attention to standards described in "Good Urodynamic Practice," establish multi-disciplinary teams for continence management and consider greater centralization of investigations for patients with neuropathies and for ambulatory studies. Most staff attended a course, yet few can describe how to zero transducers. This raises questions about the quality of reporting of some urodynamic studies. Those that are involved in urodynamics should take part in regular CME, relevant audit and consider certification and revalidation. This audit has highlighted significant variations in practice and lends support to the application of nationally agreed standards.

Conjugated linoleic acid content of beef differs by feeding regime and muscle.

The project objective was to determine the CLA content of three muscles (Longissimus lumborum, LD; Semimembranosus, SM; Triceps brachii, TB), in both raw and cooked states, in cattle finished on pasture or with grain supplements. Cattle were randomly assigned to one of four finishing regimens; pasture (n=11), pasture with grain supplement (n=11), pasture with grain supplement containing soyoil (n=12), and feedlot (n=12). In the raw state, TB had higher (P<0.05) CLA than LD or SM on a mg/g sample basis. Total CLA was higher (P<0.05) in the soyoil diet when compared to the other three feeding regimes on a mg/g sample basis and when expressed as mg/g fat in both raw and cooked analyses. Pasture inclusion produced higher levels (P<0.05) of total CLA than the feedlot diet on a mg/g fat basis for cooked samples while maintaining acceptable eating quality.

Treatment of atrophoderma of Pasini and Pierini-associated hyperpigmentation with the Q-switched alexandrite laser: a clinical, histologic, and ultrastructural appraisal.

BACKGROUND AND OBJECTIVE: Atrophoderma of Pasini and Pierini (APP) is an uncommon cutaneous disorder, with no known effective treatment, manifested by hyperpigmented patches that appear to be depressed compared with surrounding skin. This study investigated the effectiveness of the Q-switched alexandrite laser on a patient with extensive APP, and evaluated histopathologic and ultrastructural changes. STUDY DESIGN/MATERIALS AND METHODS: A man with stable APP underwent Q-switched alexandrite laser treatment to a patch on the trunk. Biopsies were obtained from treated and untreated sites of involvement. Light and transmission electron microscopic evaluation was performed to investigate melanosome number, size, and volume, as well as melanin granule number and size. RESULTS: After three treatment sessions, the treated area showed marked clinical improvement. Electron microscopy showed a 19% reduction in melanin granule number and size and a 65% reduction in melanosome number, size, and volume in larger melanosomes in treated compared with untreated sites. CONCLUSION: Treatment of APP with the Q-switched alexandrite laser results in clinical improvement. Electron microscopic evaluation suggests that the mechanism may be a reduction in the number, size, and volume of larger melanosomes as well as a decrement in melanin granule number and size.

Relative importance of quantifying area and vascular patterns in uveal melanomas.

PURPOSE: To test whether the cross-sectional area of choroidal and ciliary body melanomas and quantification of microcirculatory networks and parallel vessels with cross-linking are features associated with death from metastatic melanoma, and to compare new with conventional histologic prognostic features. METHODS: The cross-sectional area of 234 ciliary body or choroidal melanomas was measured from digitized images of histologic sections. The percentage of cross-sectional area occupied by two microcirculatory patterns-networks and parallel vessels with cross-linking-was calculated for the 152 tumors containing at least one focus of either pattern. Kaplan-Meier survival curves were generated based on cross-sectional and percentage of cross-sectional areas of these patterns. Cox proportional hazard regression methods related time to death from melanoma with sets of predictor variables. For each model, percent variation explained was computed. RESULTS: Patient survival differs significantly when tumors are classified based on cross-sectional area: small (<16 mm2), medium (> or =16 mm2 but <61.4 mm2), and large (> or =61.4 mm2). Patients with tumors containing networks and parallel vessels with cross-linking microcirculation patterns that occupy 2% of cross-sectional area have a significantly worse prognosis than do those patients with tumors containing a smaller percentage of these patterns. CONCLUSIONS: Quantifying cross-sectional tumor area and the percentage area occupied by networks and parallel vessels with cross-linking microcirculatory patterns in ciliary body and cho. roidal melanomas provides significant prognostic information. Compared with more conventional prognostic characteristics, the most dramatic increase in prognostic information is provided by determination of the presence or absence of microvascular patterns.

The dTTPase mechanism of T7 DNA helicase resembles the binding change mechanism of the F1-ATPase.

Bacteriophage T7 DNA helicase is a ring-shaped hexamer that catalyzes duplex DNA unwinding using dTTP hydrolysis as an energy source. Of the six potential nucleotide binding sites on the hexamer, we have found that three are noncatalytic sites and three are catalytic sites. The noncatalytic sites bind nucleotides with a high affinity, but dTTPs bound to these sites do not dissociate or hydrolyze through many dTTPase turnovers at the catalytic sites. The catalytic sites show strong cooperativity which leads to sequential binding and hydrolysis of dTTP. The elucidated dTTPase mechanism of the catalytic sites of T7 helicase is remarkably similar to the binding change mechanism of the ATP synthase. Based on the similarity, a general mechanism for hexameric helicases is proposed. In this mechanism, an F1-ATPase-like rotational movement around the single-stranded DNA, which is bound through the central hole of the hexamer, is proposed to lead to unidirectional translocation along single-stranded DNA and duplex DNA unwinding.

Usher's syndrome type IC: clinical studies and fine-mapping the disease locus.

Usher's syndrome type I is a heterogeneous group of diseases characterized by severe to profound sensorineural hearing loss, absent vestibular function, and progressive pigmentary retinopathy. Other identifying clinical features have not been documented. In this study, we examined olfactory acuity, plasma levels of polyunsaturated fatty acids and sarcosine, and cilia ultrastructure in a homogeneous cohort of patients with Usher's syndrome type IC. The normal age-dependent decline in olfactory acuity was observed, and normal plasma levels of polyunsaturated fatty acids and sarcosine were found. However, the incidence of compound cilia in biopsies from the inferior turbinate was significantly higher than that reported in control populations. By reconstructing haplotypes in affected persons. D11S902 and D11S1310 were identified as flanking markers over an interval that contains a candidate gene, KCNC1. No mutations in the coding sequence of this gene could be demonstrated in affected persons.

Three-dimensional relationships between tumor cells and microcirculation with double cyanine immunolabeling, laser scanning confocal microscopy, and computer-assisted reconstruction: an alternative to cast corrosion preparations.

The morphology of the microcirculation of uveal melanomas is a reliable market of tumor progression. Scanning electron microscopy of cast corrosion preparations can generate three-dimensional views of these vascular patterns, but this technique sacrifices the tumor parenchyma. Formalin-fixed wet tissue sections 100-150 microns thick from uveal melanomas were stained with the lectin Ulex europaeus agglutinin I (UEAI) and proliferating cell nuclear antigen (PCNA) to demonstrate simultaneously the tumor blood vessels and proliferating tumor cells. Indocarbocyanine (Cy3) was used as a fluorophore for UEAI and indodicarbocyanine (Cy5) was used for PCNA. Double labeled sections were examined with a laser scanning confocal microscope. Images of both stains were digitized at the same 5-microns intervals and each of the two images per interval was combined digitally to form one image. These combined images were visualized through voxel processing to study the relationship between melanoma cells expressing PCNA and various microcirculatory patterns. This technique produces images comparable to scanning electron microscopy of cast corrosion preparations while permitting simultaneous localization of melanoma cells expressing PCNA. The microcirculatory tree can be viewed from any perspective and the relationship between tumor cells and the tumor blood vessels can be studied concurrently in three dimensions. This technique is an alternative to cast corrosion preparations.

Ocular pathology of MELAS syndrome with mitochondrial DNA nucleotide 3243 point mutation.

PURPOSE: The authors describe the clinical, histopathologic, and ultrastructural findings in two eyes obtained at autopsy from a 21-year-old woman with mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS syndrome). METHODS: The eyes were obtained immediately after death. The right eye was fixed in 10% neutral-buffered formalin and processed for standard histologic examination. The left eye was fixed in a neutral-buffered 2.5% glutaraldehyde solution and processed for transmission electron microscopic examination. The authors compared the histologic and ultrastructural findings with the clinical features recorded photographically. RESULTS: The main clinical ophthalmologic features were bilateral ptosis, chronic external ophthalmoplegia, diffuse choroidal atrophy, atypical pigmentary retinopathy with macular involvement, and patchy atrophy of the iris stroma. Molecular genetic analysis detected a tRNA Leu (UUR) point mutation at position 3243 of mitochondrial DNA (MELAS genotype). Results of histologic and ultrastructural examination showed ragged-red fibers in the rectus muscles, degeneration of photoreceptor outer segments in the macula, hyperpigmentation and atrophy of the retinal pigment epithelium of the macula, atrophy of the iris stroma, early posterior subcapsular cataract, and optic atrophy. The retinal pigment epithelium, inner segments of the photoreceptors, smooth muscle cells of the choroidal and retinal vessels, the dilator and sphincter muscle of the iris, cornea, lens epithelium, and ciliary epithelium all contained many, often enlarged, structurally abnormal mitochondria with occasional paracrystalline inclusions and circular cristae. CONCLUSIONS: The MELAS-associated mitochondrial DNA nucleotide 3243 point mutation can cause a spectrum of ocular signs and symptoms that may be dependent on the patient's age and the amount of mutant mitochondrial DNA in the tissue. MELAS syndrome should be considered in the differential diagnosis of bilateral ptosis, external ophthalmoplegia, and atypical pigmentary retinopathy with macular involvement.

Clinical diagnoses of children with extremely short stature and their response to growth hormone.

This study was undertaken to determine the prevalence of clinical diagnoses in a group of children with extremely short stature (standard deviation score for height, < -2.5) and to determine whether the classification might help in predicting response to human growth hormone (hGH) treatment. We classified 49 children referred consecutively to our outpatient clinic for evaluation of short stature with heights < -2.5 standard deviation score and bone ages < 9 years for girls or < 10 years for boys (to avoid an effect of puberty on the response to hGH). The diagnostic categories were growth hormone (GH) deficiency, constitutional delay, familial short stature, and primordial short stature. After referral, Turner syndrome was diagnosed in two children. The remaining 47 children were classified according to primary criteria, considered essential for the diagnosis, and secondary criteria, considered necessary but of lesser importance. There were five children, four children, no children, and one child classified, respectively, with GH deficiency, constitutional delay, familial short stature, and primordial short stature by using the most rigorous definitions of the diagnoses. There was significant overlap in the diagnoses other than GH deficiency. Growth hormone deficiency defined by the primary criterion of peak stimulated GH values < 5 micrograms/L was the most definitive. Of the 47 children, 7 were classified as GH deficient by this criterion and 5 were classified as GH deficient by the primary and secondary criteria. The mean pretreatment growth rate (3.1 +/- 1.9 cm/yr) of the group with stimulated GH values < 5 micrograms/L was significantly less than that in the other groups (4.2 +/- 1.5 cm/yr). The mean growth rate of the children with GH deficiency during treatment with hGH was greater than that in the other groups and was 3.4 times greater than the pretreatment growth rate. The mean growth rate of children in the other groups during hGH treatment was twofold greater than the pretreatment growth rate. We conclude that except for GH deficiency, children with an extreme degree of short stature are not easily classified by standard diagnostic criteria, and that most short children have a positive response to hGH therapy regardless of the diagnosis; therefore a specific clinical diagnosis should not be used to exclude children from hGH therapy.

The morphologic characteristics of tumor blood vessels as a marker of tumor progression in primary human uveal melanoma: a matched case-control study.

Nine morphologic patterns of tumor vessels were identified in eyes removed for ciliary body or choroidal melanoma by the examination of tissue sections stained with fluorescein-conjugated Ulex europaeus I using laser scanning confocal microscopy. This technique also highlights intravascular tumor invasion. Each of these nine morphologic patterns of tumor vessels also may be demonstrated by a modification of the periodic acid-Schiff reaction, viewed with a green narrow band pass filter, but this modified histochemical technique does not accurately identify intravascular tumor invasion. Most tumors have a heterogeneous distribution of vascular patterns. Melanomas in two groups of 20 tumors each were matched by tumor size and location (one group of tumors from patients who survived at least 15 years free of metastatic melanoma after enucleation and one group of tumors from patients who died of metastatic melanoma). A matched case-control analysis indicates that the presence of at least one closed vascular loop in a uveal melanoma is the most significant vascular pattern associated with death from metastatic melanoma after enucleation. Closed loops are associated with other histologic features that are predictive of an unfavorable outcome after enucleation: epithelioid cells and mitotic figures. In this preliminary study the formation of closed vascular loops is a marker of tumor progression in ciliary body and choroidal melanomas.

Long-term treatment with growth hormone of children with short stature and normal growth hormone secretion.

Children with short stature but normal growth rate and/or normal growth hormone response to sleep and secretagogues were treated with recombinant methionyl human growth hormone, 0.3 mg/kg per week. In each year of treatment, about 80% of the subjects maintained an increase in growth rate greater than the defined limit (greater than 1 cm/yr above pretreatment growth rate) for continuation of human growth hormone treatment. Comparison of the group that continued to respond to human growth hormone with the group that did not maintain an accelerated growth rate did not reveal differences in bone age delay, sleep or secretagogue-stimulated human growth hormone secretion, degree of short stature either absolute or relative to target height, and somatomedin C concentration before or after initiation of therapy. The group that failed to respond to the human growth hormone treatment in the first year of treatment was younger and had a higher pretreatment growth rate. Review of the longitudinal growth curves revealed five patterns of response to human growth hormone treatment: (1) failure to increase growth rate in two subjects with height SD scores within 1 SD of target height, (2) failure to increase growth rate in five subjects with height SD scores greater than 1 SD less than the target height, (3) acceleration in growth rate in three subjects that was not maintained until achievement of a height within 1 SD of the target height, (4) acceleration of growth rate in five subjects that was maintained until achievement of a height within 1 SD of the target height, and (5) acceleration in growth rate that was maintained during the 3 years of treatment in 15 subjects who had not attained a height within 1 SD of the target height. We conclude that human growth hormone treatment of some but not all short children with "normal" growth hormone secretion will result in sustained acceleration of growth rate and attainment of prepubertal heights that are closer to but do not exceed their genetic height potential. A clinical trial of human growth hormone may be necessary to determine which subjects will benefit from the treatment.

Effect of immunological differences on rat aortic valve allograft calcification.

Calcification may be a cause of allograft valve degeneration. To determine whether immunological differences between donor and recipient affect the degree of calcification that occurs, adult Lewis rats received aortic valve allografts transplanted heterotopically into the abdominal aorta. All valves were transplanted immediately after harvest. The valves were not exposed to antibiotics or albumin before insertion. Valve donors were of the Lewis (syngeneic), F344 (weakly allogeneic, RT1 compatible, non-RT1 incompatible), LBN F1 (moderately allogeneic, one haplotype identical, one haplotype incompatible at the RT1 and non-RT1 loci), and Brown Norway (strongly allogeneic, RT1 and non-RT1 incompatible) strains. Valves were harvested 3-12 weeks following transplantation. Scanning electron microscopy and energy dispersion x-ray microanalysis were performed on one leaflet of each valve to evaluate calcium content. Calcium content expressed in counts (mean +/- standard error) according to donor strain were: Lewis, 1642 +/- 233; F344, 4853 +/- 1412; LBN F1, 4714 +/- 823; and Brown Norway, 4358 +/- 835. Significant differences (p less than 0.05) existed between valves from Lewis donors and those from each other strain. No differences among the other strains were statistically significant. It is concluded that syngeneic valve allografts calcify less than allogeneic grafts. However, the degree of allogenicity did not influence the magnitude of calcification.

Identification and localization of major cortical proteins in the ciliated protozoan, Euplotes eurystomus.

Shape-preserving cortical residues have been isolated from Euplotes eurystomus cells by the application of Triton X-100 at high ionic strength. These integrated structures consist of articulated plates and widely interspersed cages that formerly contained basal bodies associated with the clusters of cilia characteristic of this cell type. Using SDS-PAGE and immunolocalization procedures, we have identified major subunit proteins of both the plates (116, 110 (X10(3] Mr, and the basal body cages (86 X 10(3) Mr). The potential for studies of these proteins in contributing to our understanding of cortical development and evolution in Euplotes is discussed.

Stereologic analysis of rat type II alveolar cells in vitro.

When type II alveolar cells are maintained in culture, they gradually lose their characteristic lamellar bodies and their ability to secrete surface active material. We evaluated the feasibility of using electron microscopy and stereology to quantitate the effects of multiple culture conditions on the ultrastructure of type II alveolar cells, in vitro. The decrease in lamellar body volume density with time in culture was not affected by culturing the cells in the presence of insulin, fibronectin, or complex extracellular matrix. However, dexamethasone significantly prevented this decrease in lamellar body volume density. The mitochondrial volume density of the cells remained constant with time in culture under control conditions and in the presence of insulin, dexamethasone, or fibronectin. There was, however, a significant increase in mitochondrial volume density, for a short period of time (48 hours), when cells were cultured in the presence of complex extracellular matrix. These studies suggest that electron microscopy with stereology provides an excellent technique to quantitate in vitro ultrastructural changes in cultured type II alveolar cells.

Black thyroid syndrome: exaggeration of a normal process?

Coal-black thyroid discoloration usually is identified in patients receiving chronic minocycline therapy. This report concerns the use of light microscopic, electron microscopic, and energy dispersion spectroscopy of thyroid pigments in three separate situations: minocycline-associated black thyroid; idiopathic black thyroid; and normally pigmented thyroid glands. One of the pigments, which is found in each situation, is best described as neuromelanin. This melanin pigment, like lipofuscin, appears to accumulate with advancing age. Pigment accumulation, therefore, is a normal process in the thyroid gland. Accelerated pigment accumulation occurs with minocycline therapy but can uncommonly be seen without associated minocycline treatment. Possible mechanisms for the development of these pigments in normal and black thyroid glands are discussed. Minocycline-associated pigment is also described in substantia nigra and atherosclerotic plaques.

Demonstration of regional blood-brain barrier permeability in human brain.

The brain of a 78-year-old woman with argyria was examined at autopsy. Silver nitrate deposition was observed in circumventricular organs (CVO) and in the paraventricular and supraoptic nuclei of the hypothalamus. These findings parallel animal experiments of other investigators and are the best demonstration so far of regional absence of the blood-brain barrier in humans. These observations demonstrate similarities between humans and other mammals of CVO anatomy, permeability to blood-borne agents, and perhaps neural connections between CVOs and magnocellular nuclei.