Split-bolus single-phase versus single-bolus split-phase CT acquisition protocols for staging in patients with testicular cancer: A retrospective study.

INTRODUCTION: Computed tomography (CT) imaging has become indispensable in the management of medical oncology patients. Risks associated with high cumulative effective dose (CED) are relevant in testicular cancer patients. Split-bolus protocols, whereby the contrast medium injection is divided into two, followed by combining the required phase images in a single scan acquisition has been shown to provide images of comparable image quality and less radiation dose compared to single-bolus split-phase CT for various indications. We retrospectively evaluated the performance of split-bolus and single-bolus protocols in patients having follow-up CT imaging for testicular cancer surveillance. METHODS: 45 patients with testicular cancer undergoing surveillance CT imaging of the thorax, abdomen, and pelvis who underwent split-bolus and single-bolus protocols were included. Quantitative image quality analysis was conducted by placing region of interests in pre-defined anatomical sub-structures within the abdominal cavity. The signal-to-noise ratio (SNR) and radiation dose in the form of dose length product (DLP) and effective dose (ED) were recorded. RESULTS: The DLP and ED for the single-bolus, split-phase acquisition was 506 ± 89 mGy cm and 7.59 ± 1.3 mSv, respectively. For the split-bolus, single-phase acquisition, 397 ± 94 mGy∗cm and 5.95 ± 1.4 mSv, respectively (p < 0.000). This represented a 21.5 % reduction in radiation dose exposure. The SNR for liver, muscle and fat for the single-bolus were 7.4, 4.7 and 8, respectively, compared to 5.5, 3.8 and 7.4 in the split-bolus protocol (p < 0.001). CONCLUSION: In a testicular cancer patient cohort undergoing surveillance CT imaging, utilization of a split-bolus single-phase acquisition CT protocol enabled a significant reduction in radiation dose whilst maintaining subjective diagnostic acceptability. IMPLICATIONS FOR PRACTICE: Use of split-bolus, single-phase acquisition has the potential to reduce CED in surveillance of testicular cancer patients.

In vitro effect of cyclosporin A on primary and chronic BK polyoma virus infection in Vero E6 cells.

Cyclosporin A (CsA) is known to possess antiviral activity against several viruses in vitro, but the effect of CsA on BK polyoma virus (BKV) replication has not been examined. We investigated the impact of CsA on primary, chronic, and high-level BKV infection using a cell system of kidney cell origin (Vero E6 cells). During the first 2 h post infection, cells treated with CsA up to 3200 microg/L showed a near-identical BK viral load to untreated cells, with only a very minor reduction in the CsA-treated cells observed at 4 h. In chronic culture, CsA completely suppressed the primary BKV infection peak in a non-dose-dependent manner within the dose range of 200-12,800 microg/L (P<0.05). BKV reactivation was also inhibited in the presence of CsA at doses of 200-3200 microg/L: the mean number of BKV DNA copies/mL remained stable or even decreased slightly compared with a 7-log increase in the non-CsA group (P<0.01). CsA did not influence BKV DNA copies/mL in Vero E6 cells with high-level infection (>10(9) copies/mL). Cellular protein measurements indicated that the antiviral effect of CsA was not a result of cytotoxicity. These findings from a relevant in vitro kidney cell system indicate that CsA suppresses the primary BKV infection peak and inhibits escape to BKV reactivation; these effects are dose independent and not related to cytotoxicity. The intracellular antiviral mode of action of CsA against BKV does not appear to be via inhibition of viral cell entry pathways.

Carnitine, acylcarnitine and amino acid profiles analyzed by tandem mass spectrometry in a surfactant/virus mouse model of acute hepatic encephalopathy.

Tandem mass spectrometry (MS/MS) was used to analyze multiple serum metabolites for the first time in a surfactant/virus mouse model of acute hepatic encephalopathy (AHE). AHE is characterized by acute liver failure that can lead to potentially lethal increases in intracranial pressure. We have reproduced AHE in young CD-1 mice exposed from postnatal day (P) 2-13 to the industrial surfactant, Toximul 3409F (Tox), and then infected intranasally on P14 with sublethal doses (LD(10-30)) of mouse-adapted human influenza B (Lee) virus (FluB). The sera analyzed by MS/MS were from mice exhibiting typical markers of Tox-mediated potentiation of viral illness, including reduced weights and blood glucose levels. Most metabolite abnormalities were not evident until five days after viral infection (P19), the time corresponding to the onset of weight loss and mortality. Values for fatty acylcarnitines and amino acids in the Tox+FluB-treated mice were either additive or supra-additive relative to the effects of either treatment alone. Amino acid profiles were consistent with those reported for human AHE. None of the treated mice exhibited signs of carnitine deficiency, and propionylcarnitine levels were normal. On P19, mice given combined Tox+FluB treatment had significant increases in levels of both medium- and long-chain acylcarnitines (C6:0-C12:0 and C14:0-C20:0, respectively), including their monounsaturated metabolites. Levels of medium-chain dicarboxylic and long-chain hydroxy-acylcarnitines were also elevated in the combined treatment group. The results of this study indicate a diffuse mitochondrial dysfunction in Tox+FluB-treated mice that results in a serum metabolite profile unique from those observed in classic inherited metabolic disorders.

Utilization of vero cells for primary and chronic BK virus infection.

BK virus (BKV) nephropathy has a poor prognosis for renal allograft survival with 30% to 60% risk of allograft loss over 1 year. In the past decade, BKV nephropathy has occurred in 1% to 10% of renal transplant patients, with higher rates observed in patients with increased immunosuppression exposure and renal allograft injury. Vero cells (Green monkey kidney cell origin) were optimized for BKV primary and chronic infection inclusive of culture requirements for 60-day growth and monolayer confluence. Quantification of BKV replication in the culture supernatant (SN) and cells was by real-time polymerase-chain reaction (PCR) using the Roche Lightcycler 2.0. Primary BKV infection of Vero cells is achieved by 2 hour incubation with 6.5 x 10(5) BKV copies with subsequent washing of cells leading to steady-state cellular infection of 10(2) to 10(3) BKV copies. Primary infection is demonstrated within 7 to 10 days by a >10-fold increase of BKV copies in SN. Thereafter, a BKV viral load reduction in SN to a chronic/latent level (<10(2) BKV copies in SN) is observed by 14 days. Vero cells with chronic low-level BKV infection (10(2)-10(3) BKV copies in cells) exhibited reactivation (>10(5) BKV copies in SN) in >72% of late culture wells after 40 days. Vero cells can accommodate primary and chronic BKV infection followed by viral reactivation in late culture. The performance characteristics of 3 different pathogenic BKV strains obtained from patients with BKV nephropathy had infectivity profiles that correlated well the relative clinical profile in this Vero cell culture system.

Two formulations of the industrial surfactant, Toximul, differentially reduce mouse weight gain and hepatic glycogen in vivo during early development: effects of exposure to Influenza B Virus.

Previous studies demonstrated that young mice exposed chronically to industrial surfactant (IS) do not exhibit obvious adverse health effects, but do have persistently reduced body weights and compromised hepatic energy metabolism. The present study examined the time course of effects of two formulations of the Toximul (Tox) class of anionic/nonionic IS on body weights and liver glycogen (+/-virus) during early development. Results showed that effects differed in two commonly used strains of mice. In CFW mice, 12 days' exposure to Tox resulted in retardation of weight gain that was most obvious several days after exposure ceased. In this strain effects were greater with Tox 3409F than with Tox MP-A and appeared to be reversible except when the mice were treated with both Tox 3409F and FluB. Weights of the CD-1 mice were not affected by either Tox treatment alone, but were significantly reduced on postnatal day 20 when Tox exposure had been combined with FluB infection. Postnatal replenishment of hepatic glycogen stores during the first three weeks also occurred at different rates in CFW and CD-1 mice. The effects of Tox (+/-FluB) on glycogen also varied with mouse strain and Tox formulation. In CFW mice, exposure to either formulation resulted in significant (55-59%) reductions in glycogen, although reductions were not evident until nine days after Tox exposure stopped. By contrast, hepatic glycogen in CD-1 mice was reduced both during and after dermal exposure to Tox 3409F, whereas no effect was observed with Tox MP-A. Notably, the 3409F effect was reversible in the CD-1 mice, but reversal did not occur in mice also infected with FluB. Tox MP-A+FluB-treated mice exhibited only a transient glycogen reduction. These results illustrate the importance of mouse strain and formulation specificities in assessing biological effects of xenobiotic surfactants. As well, they emphasize that chronic IS exposure can induce changes in growth and energy substrate availability in young mice that may not be evident unless there is a precipitating cofactor such as a viral infection.

Possible reasons for the failure of glutamine to influence GABA release in rat hippocampal slices; Effect of nipecotic acid and methionine sulfoximine.

Although labelled glutamine is readily incorporated into labelled releasable GABA, it has been shown recently that high concentrations (0.1-0.5 mM) glutamine do not increase the release of GABA from brain slices, while greatly enhancing that of glutamate. Two possible reasons for this discrepancy were investigated: (a) That released GABA, in contrast to glutamate is not freshly synthesized but derives from GABA taken up by terminals. The possibility was made unlikely by the present finding which showed that even in the presence of the uptake inhibitor nipecotic acid, glutamine failed to enhance GABA release. (b) That glutamine is transported into GABA-ergic terminals by a high-affinity transport system which is saturated even at low glutamine concentrations obtained without adding glutamine to the superfusion fluid. However, when glutamine efflux was further reduced by prolonging depolarization with 50 mM K(+) and by pretreatment with the glutamine synthetase inhibitor methionine sulfoximine, GABA release was depressed only very little and this decrease was related to the duration of depolarization and not to extracellular glutamine levels. These results can be reconciled with the ready incorporation of labelled glutamine into releasable GABA by assuming that GABA originates from a glutamate pool to which both glutamine and glucose contribute. The formation of releasable GABA however, is not governed by the supply of glutamate in this pool but by the activity of the rate-limiting enzyme glutamate decarboxylase.

Coeliac disease and autoimmune Addison's disease: a clinical pitfall.

BACKGROUND: Coeliac disease has an increased prevalence in a number of autoimmune endocrine conditions. An association between coeliac disease and Addison's disease has been proposed in isolated case reports, but has not been formally studied. AIM: To investigate the extent of this association. DESIGN: Prospective screening of patients with confirmed Addison's disease. METHODS: From central computerized records, we identified all living patients with a diagnosis of autoimmune Addison's disease in the past 30 years and presently attending our affiliated hospitals. After exclusions, 44 were invited to attend for screening. RESULTS: Of 41 patients screened, five (12.2%) had coeliac disease: Three were previously diagnosed coeliacs and this was confirmed on review, including examination of biopsy material. A further two had positive IgA-endomysial antibodies. Histological confirmation was obtained in both cases. Neither had laboratory or clinical evidence of malabsorption. DISCUSSION: In this series of patients with Addison's disease, a higher co-morbidity with coeliac disease was observed than in any previously studied endocrine condition. We recommend that coeliac serology (anti-endomysial and tissue transglutaminase antibody) testing be incorporated routinely into the autoimmune screen for other conditions in patients with Addison's disease.

Increase in the stimulation-induced overflow of excitatory amino acids from hippocampal slices: interaction between low glucose concentration and fluoroacetate.

To see whether the enhanced evoked release of aspartate and glutamate in the presence of low glucose concentration is due to a decreased glial uptake, the electrical-field stimulation induced release of aspartate and glutamate was measured in rat hippocampal slices in the presence of 5 or 0.2 mM glucose and of graded concentrations of fluoroacetate, a specific inhibitor of glial tricarboxylic acid cycle. In 5 mM glucose, fluoroacetate increased the overflow of both excitatory amino acids equally in a dose-dependent manner, with a maximal effect obtained at 2 mM. This maximal increase of glutamate overflow was about the same as caused by 0.2 mM glucose, but low glucose increased aspartate overflow 5 times more than did fluoroacetate. Fluoroacetate failed to increase any further the large evoked overflow of either glutamate or aspartate induced by 0.2 mM glucose. The absence of an additive effect of fluoroacetate and of low glucose suggests that under both conditions the increased overflow of glutamate is due to a reduced glial uptake. In low glucose an increased synthesis also contributes to the additional large release of aspartate.

Effect of low glucose concentration on synaptic transmission in the rat hippocampal slice.

Severe hypoglycemia in vivo is known to slow down the EEG, then to produce complete electrical silence in the brain. To find out why low glucose concentrations reduce electrical activity, synaptic transmission from Schaffer collateral/commissural fibers to CA1 pyramidal cells in the submerged rat hippocampal slice was investigated using extracellular recording techniques. Superfusion for 30 min with 1 mM glucose reversibly reduced population spike amplitude, without affecting the size of the presynaptic volley and the slope of the field EPSP. Lower glucose concentrations also affected the EPSP, although to a lesser extent than the population spike. Antidromic population spikes were not decreased by low glucose. Depolarization with 8-10 mM K+ reduced both presynaptic volley amplitude and EPSP, but enhanced the population spike, an effect clearly different from that of low glucose. The slope of the input/output curve between presynaptic volley and EPSP remained unaltered in 1 mM glucose but the slope between EPSP and population spike was reduced by about 50%. Results suggest that low glucose concentrations interrupt synaptic transmission by reducing, but not abolishing, the excitability of pyramidal cells.

Clinical use of minoxidil (Loniten).

The powerful peripheral vasodilator minoxidil, in a dose of 5-40 mg daily, controlled the previously refractory blood pressure in 45 out of 47 patients for periods up to fifty-seven months. The majority of the previous polypharmacy was withdrawn, leaving most of the patients taking a beta-blocking drug, minoxidil and a diuretic. Severe sodium retention leading to congestive cardiac failure necessitated the withdrawal of the drug in 3 patients. In one patient the drug was discontinued because of postural hypotension, and it was withdrawn in 2 female patients because of hirsutism. Five patients were removed from the trial as they were started on chronic maintenance haemodialysis or received a renal transplant. Significant glucose intolerance developed in one patient, requiring the addition of an oral hypoglycaemic agent. The 4 deaths that occurred were not directly related to treatment. Following the oral administration of 5 mg minoxidil, an obvious reduction in both the systolic and diastolic pressure was seen in two hours.

Captopril for refractory hypertension in patients with impaired renal function.

The use of captopril in 19 patients with renal parenchymal disease and refractory hypertension was studied for a mean period of 12 months. There was a significant reduction in the systolic and diastolic blood pressures, with a reduction in the mean arterial pressure of 29 mmHg. The mean maintenance dose of captopril was 142 mg daily in three divided doses. All but one of the patients required a diuretic for satisfactory blood pressure control and 3 patients were also given a beta-blocker. In all patients a simplification of the previous therapeutic regimen was achieved. A significant rise in serum creatinine was noted in 2 patients, one of whom had to be withdrawn from the study. Despite the presence of renal functional impairment, proteinuria did not occur de novo nor did established proteinuria increase. Leukopenia was noted in any of the patients in this group.

A provincial hospital C.C.U. after ISIS 2.

A prospective study of admissions to an Irish provincial coronary care unit in the light of reported benefits of streptokinase and oral aspirin as reported in the Isis study was carried out. Of 115 patients admitted with suspected myocardial infarction (M.I.), the diagnosis was confirmed in 41. The average delay from onset of chest pain to admission to C.C.U. was 6.65 hours (0.3-18 hours, median 6 hours). Twenty-six of the 41 patients were given streptokinase after a median time lapse of six hours from the onset of pain. 88% of the M.I. patients were on oral aspirin at discharge but only 12% were on oral beta blockers. These findings are compared with the findings of the Isis 2 study worldwide and in Ireland. The presence of risk factors in the patients with M.I. is analysed, 16 of the 41 had serum cholesterol levels greater than 6 mmols/l. As an index of community risk factor screening, an enquiry was made of the patients and of their family doctor as to whether serum cholesterol had previously been checked, this had been done in only 12 of 41 and in only 2 had it been carried out by the family doctor. Pre-hospital analgesic use was also examined and 36 of the 41 patients had chest pain and were seen by their G.P.s but only 18 were given analgesics of whom 13 received morphine.(ABSTRACT TRUNCATED AT 250 WORDS)

Uncensored open access gastroscopy--limited resources--unlimited demand.

In the first 3 yr of an uncensored open access gastroscopy service in a County Hospital, 891 patients attended for first gastroscopy. The data on these patients is presented and compared with a randomly selected group who attended for gastroscopy in the yr prior to the establishment of the service having come to the normal Consultant clinics. In the open access group the gastroscopy examination was normal in 29 per cent (32 per cent comparator group), 31 per cent had major abnormalities (33 per cent comparator group) and 40 per cent had minor abnormalities (35 per cent comparator group). Delay time from referral to endoscopy was 37 days for open access patients (45 days comparator group). Only 6 per cent of open access patients were brought back to O.P.D. (47 per cent comparator group) and 72 per cent of open access patients returned directly to their family doctor (28 per cent comparator group). A comparison of the Clonmel findings with British centres reporting their results shows a broadly similar picture. It is concluded that almost 1,300 unnecessary clinic visits were avoided by the provision of the open access service, some reduction in delay time to gastroscopy was achieved, the family doctor maintained control of patient management in the great majority of patients, the pattern of referral was not inappropriate and compared very well with the comparator group. Over the 3 yr there was a large increase in the number of gastroscopies performed which caused resource difficulties. It is recommended that adequate planning of these requirements should be carried out before an open access service is started. At least 1 additional dedicated gastroscopy only endoscopy service per week would be required.