Abstracts of the 24th international isotope society (UK group) symposium: synthesis and applications of labelled compounds 2015.

The 24th annual symposium of the International Isotope Society's United Kingdom Group took place at the Møller Centre, Churchill College, Cambridge, UK on Friday 6th November 2015. The meeting was attended by 77 delegates from academia and industry, the life sciences, chemical, radiochemical and scientific instrument suppliers. Delegates were welcomed by Dr Ken Lawrie (GlaxoSmithKline, UK, chair of the IIS UK group). The subsequent scientific programme consisted of oral presentations, short 'flash' presentations in association with particular posters and poster presentations. The scientific areas covered included isotopic synthesis, regulatory issues, applications of labelled compounds in imaging, isotopic separation and novel chemistry with potential implications for isotopic synthesis. Both short-lived and long-lived isotopes were represented, as were stable isotopes. The symposium was divided into a morning session chaired by Dr Rebekka Hueting (University of Oxford, UK) and afternoon sessions chaired by Dr Sofia Pascu (University of Bath, UK) and by Dr Alan Dowling (Syngenta, UK). The UK meeting concluded with remarks from Dr Ken Lawrie (GlaxoSmithKline, UK).

Isolated hepatic perfusion for ocular melanoma metastasis: registry data suggests a survival benefit.

BACKGROUND: Uveal melanoma is the most common primary intraocular malignancy in adults. Despite successful control of the primary tumor, metastatic disease will ultimately develop in approximately 35% of the patients, with the liver being the most common site for metastases. These metastases are generally refractory to systemic chemotherapy, and the median survival for patients with liver metastases is about 6 months. This phase II trial reports the experience of isolated hepatic perfusion (IHP) as a treatment option. METHOD: A total of 34 patients with isolated liver metastasis from ocular melanoma underwent IHP. An overall survival comparison was made using data retrieved from the National Patient Register managed by the Swedish National Board of Health and Welfare. RESULTS: An overall radiological response was seen in 68% of the patients, with 12% having a complete response. Time to local progression was 7 months; 68% of the patients developed extrahepatic metastases after a median of 13 months, and the median overall survival was 24 months. There was a significant survival advantage of 14 months (p = 0.029) when comparing these patients with a control group consisting of the longest surviving patients in Sweden with uveal melanoma liver metastases not treated with IHP. CONCLUSIONS: IHP is a treatment option with a high response rate and a potential survival benefit of more than 1 year. IHP should be considered an option in the treatment of uveal melanoma metastases. A randomized trial comparing IHP and best alternative care will start during 2013 (the SCANDIUM trial, ClinicalTrials.gov identifier NCT01785316).

Diagnostic incisional biopsies in clinically indeterminate choroidal tumours.

Most intraocular tumours are reliably diagnosed by a careful clinical examination combined with one or more non-invasive diagnostic techniques. However, in a small percentage of tumours, typically small and clinically amelanotic, the features are insufficiently distinct for a confident clinical diagnosis and tissue is required for diagnosis. We used a 23-G vitreous cutter to access the biopsy site in 43 patients with clinically indeterminate tumours. After retinotomy, an incisional choroidal biopsy yielded a specimen of ∼1 mm(3). Obtained tissue was routinely processed for light microscopy including an immunohistochemical panel of monoclonal antibodies. Adequate tissue for diagnosis was provided in 41/43 (95%) patients. The sensitivity and specificity to detect malignant disease were 0.97 and 1.00, respectively. The positive predictive value was 1.00. Complications included progression of pre-existing retinal detachment in 5/43 (12%) patients and transient rise in intraocular pressure to >40 mm Hg in 6/43 (14%) patients; 4 of these 6 patients had a pre-existing retinal detachment. No patient with a pre-operatively attached retina had a retinal detachment. We conclude that an incisional transretinal choroidal biopsy yields abundant material and may adequately confirm or exclude malignancy in patients with clinically indeterminate tumours. The complication rate can be minimised when patients with pre-existing retinal detachment are excluded from biopsy.

Time trends in the incidence of conjunctival melanoma in Sweden.

AIM: To study time trends in the incidence of conjunctival melanoma in Sweden. METHODS: All patients with conjunctival melanoma from 1960 to 2005 in Sweden were identified through the Swedish Cancer Registry, cross-checked against hospital files, and validated by histopathological review (97.5%) or detailed hospital records (2.5%). The crude and age-standardised incidences were estimated separately for each sex and the annual change in incidence over time was estimated using a regression model with logarithmic incidence numbers. Time trends for the largest diameter, thickness and location of the tumour when diagnosed were analysed. RESULTS: The age-standardised incidence of conjunctival melanoma increased significantly in men (n = 89) from 0.10 cases/million to 0.74 cases/million (p = 0.001) and in women (n = 81) from 0.06 cases/million to 0.45 cases/million (p = 0.007). The annual relative change in age-standardised incidence was 16.9% (95% confidence interval (CI) 12.2 to 21.6) in men and 19.5% (95% CI 9.3 to 29.7) in women. The age-specific incidence was higher in men and women > or = 65 years (1.48 and 1.39 cases/million, respectively) than in younger men and women (0.3 and 0.2 cases/million, respectively). During the period of study, tumours became smaller (p = 0.005) and thinner (p = 0.002) at the time of diagnosis and increasingly arose from parts of the conjunctiva exposed to ultraviolet radiation (p = 0.001). CONCLUSION: The incidence of conjunctival melanoma increased in Sweden during the period 1960 to 2005.

Peritonectomy with high voltage electrocautery generates higher levels of ultrafine smoke particles.

BACKGROUND: To adequately perform peritonectomy, the use of an electrocautery device at a high voltage is recommended. The aim of this study was to analyse the amount of airborne and ultrafine particles (UFP) generated during peritonectomy and to compare this with standard colon and rectal cancer surgery (CRC). METHOD: UFP was measured approximately 2-3 cm from the breathing area of the surgeon (personal sampling) and 3 m from where the electrocautery smoke was generated (stationary sampling) from 14 consecutive peritonectomy procedures and 11 standard CRC resections. The sampling was by P-Trak UFP counter that has the capacity to detect particle size ranging from 0.02 to 1 microm. RESULTS: The cumulative level of UFP of personal sampling in the peritonectomy group was higher (9.3 x 10(6) particle/ml/h (pt/ml/h)) than in the control group (4.8 x 10(5) pt/ml/h). A higher cumulative level of UFP in stationary sampling was observed in the PC group (2.6 x 10(6) pt/ml/h) than in the control group (3.9 x 10(4)pt/ml/h). CONCLUSION: Peritonectomy procedure with high voltage electrocautery generates elevated levels of UFP than standard CRC surgery does. The level of UFP produced by a peritonectomy is comparable to cigarette smoking. More efficient smoke evacuator systems are needed in order to reduce the levels of UFP generated during electrocautery surgery.

Lower serum concentration of matrix metalloproteinase-3 in the acute stage of myocardial infarction.

OBJECTIVES: The importance of matrix metalloproteinases (MMPs) in the progression and rupture of the atherosclerotic plaque is gaining increasing recognition but the mechanisms are not yet fully understood. The aim of this study was to investigate the significance of MMP-3 in the acute phase of myocardial infarction (MI) and the influence of the -1612 5A/6A MMP-3 gene promoter polymorphism on serum MMP-3 concentration. SUBJECTS: One-hundred and sixty-four patients admitted with ST-elevation MI and receiving thrombolysis treatment were included in this study. Serum MMP-3 was analysed at admission, after 48 h and at 3 months. RESULTS: Serum MMP-3 concentration was significantly increased at 3 months when compared with admission and 48 h (19.5 ng mL(-1) [14.4-24.7] vs. 15.5 ng mL(-1) [10.5-21.8] at admission, P < 0.001; and 14.7 ng mL(-1) [9.9-23.8] at 48 h, P < 0.001). Furthermore, we found the -1612 5A/6A polymorphism to influence the serum concentration of MMP-3 at all time-points: 14.1 ng mL(-1) [10.2-18.8] in 5A/5A; 19.6 ng mL(-1) [15.0-24.4] in 5A/6A; and 24.0 ng mL(-1) [20.1-32.3] in 6A/6A genotype at 3 months (P < 0.001 between all groups). Female patients had lower serum MMP-3 concentration than male patients at all time-points (14.8 ng mL(-1) [9.4-20.8] vs. 19.9 ng mL(-1) [16.0-26.9], P < 0.0001 at 3 months). CONCLUSIONS: Serum concentration of MMP-3 is significantly lower in the acute stage of MI than during recovery and is significantly influenced by -1612 5A/6A genotype and gender. Together with previous findings, these results primarily implicate MMP-3 in atherosclerosis progression rather than in acute MI.

Serum matrix metalloproteinase-3 concentration is influenced by MMP-3 -1612 5A/6A promoter genotype and associated with myocardial infarction.

OBJECTIVES: Matrix metalloproteinase-3 (MMP-3) is implicated in the formation of atherosclerotic plaques, and the MMP-3 -1612 5A/6A polymorphism is associated with myocardial infarction (MI) and stable coronary artery disease (CAD). The present study examined whether the -1612 5A/6A polymorphism in the promoter region of the MMP-3 gene influences serum concentrations of MMP-3 and whether serum concentrations of MMP-3 are related to extent of coronary atherosclerosis and risk of MI. DESIGN AND SUBJECTS: This case-control study was conducted in three hospitals in the northern part of Stockholm. A total of 755 MI patients aged below 60 were screened, 433 entered and 387 completed the study. Three hundred and eighty-seven sex- and age-matched control subjects were recruited from the general population of the same county. METHODS: The MMP-3 genotype was determined by Pyrosequencing(TM) and the serum MMP-3 concentration was quantified with an immunoassay. Severity and extension of CAD was assessed by quantitative coronary angiography in a subgroup of patients (n=243). RESULTS: Patients had lower serum MMP-3 concentration than controls. There was a strong association between MMP-3 -1612 5A/6A genotype and serum concentrations of MMP-3. The presence of one or two copies of the 6A-allele was associated with a graded increase in serum MMP-3. In female patients there was an inverse correlation (r=-0.39, P<0.05) between serum MMP-3 concentration and plaque area. Conclusion. In conclusion, the serum concentration of MMP-3 is influenced by MMP-3 -1612 5A/6A genotype and associated with MI.

Prognostic value of plasma C-reactive protein and fibrinogen determinations in patients with acute myocardial infarction treated with thrombolysis.

OBJECTIVES: To investigate the prognostic value of plasma C-reactive protein (CRP) and fibrinogen determinations in patients with acute myocardial infarction treated with thrombolysis. DESIGN: Longitudinal study of morbidity and mortality. SETTING: Coronary care unit at Danderyd Hospital, Stockholm, Sweden. SUBJECTS: A total of 222 patients aged 75 years or below, treated with thrombolysis because of typical symptoms of myocardial infarction and electrocardiogram showing ST-segment elevation or bundle branch block were included in the study. The patients were followed for 24-60 months (mean 40 +/- 16 months). MAIN OUTCOME MEASURES: Cardiovascular death or new myocardial infarction. RESULTS: Concentrations of CRP were significantly higher at 48 h than at 3 months, whilst the levels of fibrinogen were similar. CRP and fibrinogen concentrations measured during the acute phase of myocardial infarction were associated with cardiovascular death or a new myocardial infarction during follow-up in univariate analysis. CRP levels measured 3 months after the acute event were not associated with subsequent events whereas fibrinogen concentrations showed a borderline prognostic significance (P = 0.05). When CRP and fibrinogen were entered into multivariate analysis together with the previously established prognostic factors in the patient group (age, diabetes mellitus and left ventricular function), these markers of inflammation did not add further prognostic information. CONCLUSION: C-reactive protein and fibrinogen do not carry the same independent prognostic information after acute myocardial infarction treated with thrombolysis as in studies previously reported for patients with unstable angina or non-Q-wave myocardial infarction.

Rifaximin versus ciprofloxacin for the treatment of traveler's diarrhea: a randomized, double-blind clinical trial.

Rifaximin is a poorly absorbed rifamycin derivative under investigation for treatment of infectious diarrhea. Adult students from the United States in Mexico and international tourists in Jamaica were randomized to receive either rifaximin (400 mg twice per day) or ciprofloxacin (500 mg twice per day) for 3 days, following a double-blinded model, from June 1997 to September 1998. A total of 187 subjects with diarrhea were studied. Time from initiation of therapy to passage of last unformed stool was comparable for those receiving rifaximin or ciprofloxacin (median, 25.7 hours versus 25.0 hours, respectively). There was no significant difference in the proportion of subjects in the 2 groups with respect to clinical improvement during the first 24 hours (P=.199), failure to respond to treatment (P=.411), or microbiological cure (P=.222). The incidence of adverse events was low and similar in each group. Rifaximin is a safe and effective alternative to ciprofloxacin in the treatment of traveler's diarrhea.

Diastereocontrol by trialkylaluminums in the synthesis of tetrahydrofurans via radical cyclization.

[reaction: see text]. The influence of various Lewis acids in the radical cyclization of beta-allyloxyalkyl phenyl selenides was investigated. Whereas the unperturbed cyclization afforded trans-2,4-disubstituted tetrahydrofurans as the major products (cis/trans approximately 1/4.5), cyclization in the presence of trialkylaluminums (3 equiv) afforded predominantly (cis/trans approximately 7/1) the corresponding cis-isomers.

Association of HLA class I and class II antigen expression and mortality in uveal melanoma.

PURPOSE: Malignant transformation of cells is frequently associated with abnormalities in human leukocyte antigen (HLA) expression. These abnormalities may play a role in the clinical course of the disease, because HLA antigens mediate interactions of tumor cells with T cells and NK cells. Uveal melanoma is a highly malignant tumor of the eye and is characterized by a hematogenic spread to the liver. Little is known about the role of HLA expression in progression of this malignant disease. METHODS: In the present study HLA class I antigen, beta(2)-microglobulin (beta(2)-m), and HLA class II antigen expression was analyzed in primary uveal melanoma lesions by immunoperoxidase staining with monoclonal antibodies of 65 archival clinical samples. The results were correlated with the clinical course of the disease. RESULTS: HLA class I antigen expression and beta(2)-m expression were downregulated in 40 and 35 lesions, respectively. HLA class II antigens were expressed in 30 lesions. Patients with high HLA class I, including beta(2)-m, and HLA class II antigen expression in their primary melanoma lesions had a significantly decreased survival (P = 0.009, P < 0.001, and P = 0.006, respectively). CONCLUSIONS: The findings argue against a major role of cytotoxic T-lymphocyte (CTL)-mediated control of tumor growth in the clinical course of uveal melanoma and are compatible with a potential role of NK-cell-mediated control of hematogenic metastatic spread.

Native valve endocarditis due to Bartonella henselae in a middle-aged human immunodeficiency virus-negative woman.

We report the case of a human immunodeficiency virus-negative woman who developed native valve endocarditis of the aortic valve due to Bartonell henselae infection. The diagnosis was established using serology and PCR analysis of excised aortic valve tissue.

Successful treatment of vancomycin-resistant Enterococcus faecium meningitis with linezolid: case report and literature review.

Vancomycin-resistant enterococci (VRE) are a rare cause of meningitis, occurring primarily in patients who have undergone neurosurgical procedures. We describe the first reported case of VRE meningitis successfully treated with linezolid. A 56-y-old female with subarachnoid hemorrhage underwent ventriculostomy and embolization of cerebral aneurysms. Her postoperative course was complicated by multiple infections needing repeated antibiotic courses, culminating in the development of VRE meningitis. She was treated with 600 mg of i.v. linezolid (MIC < 0.75 microg/ml) every 12 h for 6 weeks. After the fourth dose, peak and trough linezolid concentrations were 11.45 and 0.14 microg/ml in serum and 3.19 and 2.39 microg/ml in cerebral spinal fluid (CSF). On Day 19 of linezolid therapy, serum and CSF trough concentrations were 1.53 and 2.98 microg/ml, respectively. Linezolid achieved sufficient CSF concentrations to bring about clinical and bacteriological cure. We conclude that i.v. linezolid may be a useful option for treating VRE meningitis. We also present findings of a literature review, which identified 11 cases of VRE meningitis treated with other pharmacologic agents with mixed success.

Enteroaggregative Escherichia coli as a major etiologic agent in traveler's diarrhea in 3 regions of the world.

Enteroaggregative Escherichia coli (EAEC) has been reported to cause traveler's diarrhea and persistent diarrhea in children in developing countries and in immunocompromised patients. To clarify the prevalence of EAEC in traveler's diarrhea, we studied 636 US, Canadian, or European travelers with diarrhea: 218 in Guadalajara, Mexico (June--August 1997 and 1998), 125 in Ocho Rios, Jamaica (September 1997--May 1998), and 293 in Goa, India (January 1997--April 1997 and October 1997--February 1998). Stool samples were tested for conventional enteropathogens. EAEC strains were identified by use of the HEp-2 assay. EAEC was isolated in 26% of cases of traveler's diarrhea (ranging from 19% in Goa to 33% in Guadalajara) and was second only to enterotoxigenic E. coli as the most common enteropathogen in all areas. Identification of EAEC reduced the number of cases for which the pathogen was unknown from 327 (51%) to 237 (37%) and explained 28% of cases with unknown etiology. EAEC was a major cause of traveler's diarrhea in 3 geographically distinct study areas.

Emergence of trimethoprim-resistant Escherichia coli in healthy persons in the absence of prophylactic or therapeutic antibiotics during travel to Guadalajara, Mexico.

Thirty-nine healthy US students without diarrheal disease and who had not received prophylactic or therapeutic antibiotics were monitored for emergence of trimethoprim-resistant gram-negative fecal flora for a 3-week period after arrival in Guadalajara, Mexico. During this time period, most students showed no change in total fecal gram-negative bacteria (p > 0.05) but showed an increasing level of trimethoprim (TMP) resistance (p < 0.01) among fecal coliforms. Escherichia coli was the TMP-resistant organism isolated in 18 of 39 (46%) healthy students. These 18 TMP-resistant E. coli were also resistant to ampicillin (44%), azithromycin (11%), chloramphenicol (39%), ciprofloxacin (11%), doxycycline (89%), erythromycin (100%), furazolidone (72%), levofloxacin (17%), trimethoprim-sulfamethoxazole (89%) and trovafloxacin (17%). In the absence of prophylactic and therapeutic antibiotics, increased acquisition of TMP-resistant gram-negative fecal flora in this developing country is probably due to poor sanitary conditions and the recurrent and heavy exposure to antimicrobial-resistant indigenous flora as a result of contaminated food and drink.

Empirical antimicrobial therapy for traveler's diarrhea.

Over 7 million cases of traveler's diarrhea, defined as the passage of > or = 3 unformed stools in a 24-h period, occur each year among visitors to developing countries. Bacterial enteric pathogens are the most common etiologic agents isolated. Preliminary clinical results for patients with diarrhea predominantly caused by Campylobacter species have shown that azithromycin may be an effective alternative to fluoroquinolones for the treatment of traveler's diarrhea.