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.

Serious lead poisoning in childhood: still a problem after a century.

OBJECTIVE: To describe a series of patients with clinically significant lead poisoning. METHODOLOGY: A case series of nine patients with lead poisoning who required inpatient management, identified through a Clinical Toxicology Service. RESULTS: Nine children presented with clinically significant lead poisoning. The median serum lead was 2.5 micro mol/L (range 1.38-4.83). Eight of the children were exposed to lead-based paint, with seven due to dust from sanded lead paint during house renovations. Serial blood determinations suggested re-exposure in four of the patients, and in one of these patients the re-exposure was from a different source of lead. Eight of the patients required chelation therapy. CONCLUSIONS: Serious lead poisoning continues to occur and there appears to be complacency regarding the hazard posed by lead paint in old houses.

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.

XRCC2 is a nuclear RAD51-like protein required for damage-dependent RAD51 focus formation without the need for ATP binding.

The human XRCC2 gene was recently identified by its ability to complement a hamster cell line, irs1, which is sensitive to DNA-damaging agents and shows genetic instability. The XRCC2 protein is highly conserved in mammalian species and has structural features, including a putative ATP-binding domain (P-loop), consistent with membership of the RecA/RAD51 family of recombination-repair proteins. We show that a hybrid XRCC2-green fluorescent protein, which was found to be functional by complementation, localizes to the nucleus. We have established a functional link between XRCC2 and RAD51 by looking at damage-dependent RAD51 focus formation in the irs1 cell line. Little or no formation of RAD51 foci occurred in irs1. This effect was specific to the loss of XRCC2 because transfection of the gene into irs1 restored normal levels of focus formation. Surprisingly, XRCC2 genes carrying site-specific mutations in P-loop residues were found to be able to complement the XRCC2-deficient irs1 line for a number of different end points. We conclude that XRCC2 is important in the early stages of homologous recombination in mammalian cells to facilitate RAD51-dependent recombination repair but that it does not make use of ATP binding to promote this function.

Disposable device and a minimally invasive technique for rubber band ligation of hemorrhoids.

A disposable syringe-like hemorrhoid ligator was invented to simplify the banding procedure for both patient and surgeon. This single-operator ligator, with its own suction mechanism and easy loading features, was designed for use without the need of an assistant or an anoscope. By pointing the ligator directly toward the appropriate site and by measuring the distance from the anal margin using reference markings on the ligator, the bands can be placed accurately in a blind manner inside the rectum for the treatment of symptomatic internal hemorrhoids. Before the band is discharged, rotating the ligator through 180 degrees while applying suction will cause pain and give warning if the application site is not appropriate. In 480 patients treated to date, this technique was found to be well accepted and accurate, and the final results seem to be comparable to other methods of banding.

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.

MALTectomy (appendectomy/tonsillectomy) does not influence the occurrence or mode of presentation of adult celiac disease.

OBJECTIVE: Recent reports suggest that appendectomy may protect against the development of ulcerative colitis. Depletion of mucosal helper T-cells is the suggested mechanism. Because mucosal T-cell activity has an even more critical role in the pathogenesis of celiac disease, our objective was to determine whether the development or mode of presentation of this disorder is influenced by appendectomy and/or tonsillectomy. METHODS: One hundred fifty consecutive adult celiac patients were compared with 138 consecutive patients examined at orthopedic clinics. One hundred twenty consecutive patients with ulcerative colitis from the same ethnogeographic population were included as positive disease control. RESULTS: Contrary to the previous findings in ulcerative colitis, which were again confirmed in this study, appendectomy and/or tonsillectomy did not influence the occurrence of celiac disease. In addition, presenting features, predefined in the study protocol, did not differ significantly in the appendectomy and nonappendectomy celiac patients. CONCLUSION: Resection of mucosa-associated lymphoid tissue (MALT) does not influence the occurrence or the mode of presentation of adult celiac disease. Therefore, in this classical example of a T-cell-mediated disorder, the hypothesis that surgical depletion of mucosal T-cells has a protective effect or influences the clinical manifestations cannot be supported.

Laparoscopic appendectomy: a review of 95 consecutive suspected cases of appendicitis.

OBJECTIVE: To assess the feasibility and efficacy of laparoscopic appendectomy. DESIGN: A review of a case series. SETTING: A single teaching and referral centre in Vancouver. PATIENTS: Ninety-five consecutive patients referred to the Division of General Surgery with suspected appendicitis requiring surgical intervention. The patients ranged in age from 15 to 85 years. INTERVENTIONS: Laparoscopic appendectomy or open appendectomy. MAIN OUTCOME MEASURES: Feasibility of laparoscopic appendectomy, duration of operation, intraoperative and postoperative complications and duration of postoperative hospital stay. RESULTS: Of the 95 patients, 9 had contraindications to laparoscopic appendectomy and underwent an open operation. Of the 86 patients who underwent laparoscopy, the diagnosis of appendicitis was confirmed in 69 (80%). Following this, 61 (88%) patients underwent laparoscopic appendectomy, and in 8 the procedure was converted to open appendectomy because of periappendiceal abscess or an immobile or perforated appendix. The mean duration of operation was 78.5 minutes. There were no intraoperative complications. The mean duration of postoperative hospital stay was 2.8 days. Postoperative complications consisted of ileus in two patients and diarrhea in two patients. There were no wound infections. CONCLUSIONS: Laparoscopic appendectomy can be performed safely, with minimal complications on most patients with appendicitis; hospital stay is reduced. Laparoscopy allows accurate diagnosis.

A pig model for advanced laparoscopic biliary procedures.

Advanced laparoscopic biliary procedures can be undertaken in a pig model, but the small size of the normal common bile duct makes learning difficult. We have developed a prepared pig model of common bile duct ligation on which to practice advanced laparoscopic biliary surgery. The pig's distal common bile duct was occluded using several different methods via a minilaparotomy. Laparoscopic biliary procedures were undertaken 6-21 days later. The common bile duct became dilated to between 2 and 3 cm in diameter in all cases, and this was well tolerated by the animals. All advanced laparoscopic biliary procedures were possible, including choledochoscopy, exploration of the bile duct, and cholecystojejunostomy. Short-term common bile duct ligation is well tolerated in pigs and can be used to create a model for practicing advanced laparoscopic biliary procedures.

Melanocytic naevi and melanoma in survivors of childhood cancer.

There is evidence from previous studies of small numbers of children who received cytotoxic therapy for cancer, that they may develop increased numbers of melanocytic naevi (moles), the strongest known risk factors for melanoma. Our aim was to investigate a large number of survivors of childhood cancer in order to test the hypothesis that they have more melanocytic naevi than matched controls. Total-body naevus counts were obtained from 263 oncology patients ascertained in paediatric oncology departments in Queensland, Australia, and from 263 hospital controls matched for age and sex. Additional information was gathered from children's parents about concurrent factors influencing naevus development such as type of complexion and history of sun exposure. Matched analyses, both crude and adjusted for possible confounding factors, revealed no significant difference in overall density of naevi among oncology patients and control subjects, according to diagnosis or to duration or type of chemotherapy. However significantly more oncology patients had atypical naevi (P < 0.05) and acral naevi (P < 0.0001) than controls. One patient developed a malignant melanoma 13 years after chemotherapy and radiotherapy for rhabdomyosarcoma. These findings support an association between treatment for childhood cancer and acral naevi and suggest that atypical naevi may also be associated with chemotherapy in childhood.

Laparoscopic gastrointestinal anastomoses.

In a preliminary study of laparoscopic gastrointestinal anastomosis, a gastric outlet obstruction was created under laparoscopic control in six domestic pigs, weighing an average of 25 kg. A simultaneous gastroenterostomy was formed with an end-stapling device. All animals recovered clinically, and good anastomotic healing was documented 1 week postoperatively. The authors suggest that an end-stapling device could be one method of creating a gastrointestinal anastomosis for humans that is safe and reliable, allows rapid recovery and decreases hospital stay.

Laparoscopy in General Surgery: The pros and cons of endoscopic surgery.

After a period of rather slow initial acceptance by general surgeons, laparoscopy and video endoscopic surgery have suddenly burst on to the surgical scene. Almost overnight many of the surgical procedures once requiring a large incision are now being performed through small punctures. This article describes some of the more common procedures and discusses the merits and difficulties associated with these innovations.

Laparoscopic appendectomy.

In October 1989 the author began a study of laparoscopic appendectomy. This paper presents the preliminary results in 21 patients. Laparoscopy was carried out for diagnosis and 12 patients underwent laparoscopic appendectomy. The morbidity, length of hospital stay and time lost from work was reduced in all 12 patients. The author describes the technique of laparoscopic appendectomy and recommends that only experienced laparoscopists should carry out this procedure.

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)

Alloimmune neonatal neutropenia in Australian aboriginals: an unrecognized disorder?

Alloimmune neonatal neutropenia (ANN) is reported for the first time in two Australian aboriginals. Both infants displayed the typical clinical features of ANN with profound neutropenia which persisted for 7 weeks and only minor infectious episodes. However, management strategies differed for the two infants because in one case (complicated by uncertain paternity) serological confirmation of ANN was not obtained until after recovery of the infant's neutrophil count. The maternal antibodies could not be assigned to known neutrophil antigen specificities and a new antigen may be involved. The antibodies were reactive with > 99% of neutrophils in a Caucasian population. Aboriginals comprise 1% of the total population of Australia and 1-2% of the obstetric population at our institution. Thus, ANN may be an unrecognized disorder in this ethnic group and a possible cause of neonatal infection and mortality.