High serum lactate as an adjunct in the early prediction of anastomotic leak following oesophagectomy.

BACKGROUND: Anastomotic leak (AL) following oesophagectomy carries a high mortality and morbidity. Early detection and intervention is required for a successful outcome. We have examined the role of a high postoperative serum lactate in predicting which patients are at risk of developing an anastomotic leak(AL). MATERIALS AND METHODS: All patients who underwent transthoracic oesophagectomy over a 3-year period were identified from a prospectively collected database. Medical records were reviewed to identify the highest serum lactate recorded from blood gas analysis over each 24hr post-operative period. Patients who underwent transhiatal and left thoraco-abdominal oesophagectomies were excluded. Patients who developed a chyle leak were excluded. RESULTS: Of a total of 136 oesophagectomies included for analysis, 18 developed an AL (13.2%). Of these patients, 10 underwent thoracoscopic oesophageal mobilization with cervical anastomosis and the rest an Ivor Lewis procedure. Predictive factors for AL included neoadjuvant chemotherapy (15/18 83.3% vs 55/118 46.6% p = 0.0046) and number of positive lymph nodes (mean 4.2 vs control mean 2.3 p = 0.045). Overall net fluid balance was comparable between the 2 groups, although AL patients received slightly more fluid on Day 3. High lactate levels on days 1-3 were associated with an AL. Using a Day 2 lactate of 1.7 mmol/L, the sensitivity of predicting AL was 72% and specificity 88%. The mean lag time using existing diagnostic modalities was 7.9 days. CONCLUSION: A serum lactate of >1.7 mmol/l on day 2 should raise the possibility of a potential AL. Such patients should be selected for more intensive monitoring, optimization and selective gastroscopy.

Investigation of outbreaks of Pneumocystis jirovecii pneumonia in two Scottish renal units.

Pneumocystis jirovecii is recognized as an opportunistic pathogen. In recent years, human-to-human transmission of P. jirovecii has been demonstrated. However, outbreaks of P. jirovecii infections are not well defined because the epidemiological setting that facilitates transmission is not fully understood. This article describes two outbreaks of P. jirovecii pneumonia (PCP) in renal transplant patients in the West of Scotland. In total, 25 patients in two geographically contiguous locations were affected. Allele B was identified as the dominant type, along with allele A3. It was not possible to determine the exact reason for clustering of cases, although the outpatient clinic setting featured in one of the outbreaks. The outbreaks ceased with the use of trimethoprim-sulphamethoxazole prophylaxis; the target populations that received prophylaxis were different in the two outbreaks. Infection control teams should be alert to the possibility of outbreaks of PCP.

Determining the effect of social deprivation on the prevalence of healthcare-associated infections in acute hospitals: a multivariate analysis of a linked data set.

BACKGROUND: Healthcare-associated infections (HCAIs) endanger safety by increasing morbidity, mortality, and hospital stay. Studies identifying risk factors for HCAI rarely address the wider determinants of health. However, a well-characterized association exists between increasing social deprivation and poor health outcomes. Therefore it is important to determine whether HCAIs are associated with social deprivation. AIM: To determine the association between social deprivation and the prevalence of HCAI, in all inpatients in an acute hospital in Scotland on a single day across September and October 2011. METHODS: This study linked Scottish data from the 2011 European Point Prevalence Survey of HCAI and Antimicrobial Prescribing to the Scottish Morbidity Record 01, a national dataset with Scottish Index of Multiple Deprivation (SIMD) included. Multivariate logistic regression was used to model HCAI prevalence against SIMD quintile. FINDINGS: No overall association was found between SIMD quintile and prevalence of HCAI in all inpatients. A significant difference was found between HCAI prevalence across SIMD quintile in patients undergoing surgical procedures, with higher prevalence observed with increasing deprivation (P = 0.0071). Variables associated with HCAI prevalence were: intensive care specialty, psychiatric and medical specialties, minimum invasive surgery, and all categories of length of stay. CONCLUSION: This study found a significant difference in HCAI prevalence across SIMD quintile in patients undergoing surgery. To our knowledge this was the first study to examine the overall association between HCAI and SIMD. The findings highlight the broad and comprehensive nature of social deprivation in determining health outcomes.

The inability of a bacteriophage to infect Staphylococcus aureus does not prevent it from specifically delivering a photosensitizer to the bacterium enabling its lethal photosensitization.

OBJECTIVES: It has been demonstrated that the efficiency of lethal photosensitization can be improved by covalently binding photosensitizing agents to bacteriophage. In this study we have investigated whether a bacteriophage requires the capacity to infect the bacterium to enhance lethal photosensitization when linked to a photosensitizer. METHODS: Tin (IV) chlorin e6 (SnCe6) was conjugated to bacteriophage Phi11, a transducing phage that can infect Staphylococcus aureus NCTC 8325-4, but not epidemic methicillin-resistant S. aureus (EMRSA)-16. The conjugate and appropriate controls were incubated with these bacteria and either exposed to laser light at 632.8 nm or kept in the dark. RESULTS: The SnCe6/Phi11 conjugate achieved a statistically significant reduction in the number of viable bacteria of both 8325-4 and EMRSA-16 strains by 2.31 log(10) and 2.63 log(10), respectively. The conjugate could not however instigate lethal photosensitization of Escherichia coli. None of the other combinations of controls, such as an equivalent concentration of SnCe6 only, an equivalent titre of bacteriophage only or experiments conducted without laser light, yielded significant reductions in the number of viable bacteria recovered. CONCLUSIONS: The inability of a bacteriophage to infect S. aureus does not prevent it from specifically delivering a photosensitizer to a bacterium enabling its lethal photosensitization.

Renal injury: similarities and differences in male and female rats with the metabolic syndrome.

The metabolic syndrome is complicated by nephropathy in humans and rats, and males are more affected than females. We hypothesized that female rats had reduced expression of glomerular oxidized low-density lipoprotein (oxLDL) receptor 1 (LOX-1), attendant glomerular oxidant injury, and renal inflammation. Three groups, obese males (OM), obese females (OF), and lean males (LM) of first-generation (F(1)) hybrid rats derived from the Zucker fatty diabetic (ZDF) strain and the spontaneous hypertensive heart failure rat (SHHF/Gmi-fa) were studied from 6 to 41 weeks of age. OM had severe renal oxidant injury and renal failure. Their glomeruli expressed the LOX-1, and exhibited heavier accumulation of the lipid peroxide 4-hydroxynonenal (4-HNE). OM had compromised mitochondrial enzyme function, more renal fibrosis, and vascular leakage. Younger LM, OM, and OF ZS (ZDF/SHHF F(1) hybrid rat) rats, studied from 6 to 16 weeks of age, showed that unutilized renal lipids were comparable in OM and OF, although young OM had worse nephropathy and inflammation. In conclusion, glomerular LOX-1 expression is coupled to deposits of 4-HNE and glomerulosclerosis in OM. We presume that LOX-1 enhances glomerular uptake of oxidized lipids and renal inflammation, causing greater oxidant stress and severe glomerulosclerosis. In OF, renal protection from lipid oxidants appears to be conferred by blunted glomerular LOX-1 expression and renal inflammation.

Radioactive waste discharge quantities for patients undergoing radioactive iodine therapy for thyroid carcinoma.

There is a need to provide realistic estimates of the activity discharged to the drains by patients undergoing procedures involving unsealed radionuclides. These estimates are essential for record keeping purposes, to demonstrate compliance with limits set in waste disposal authorizations and for planning new installations. In this study, we report the discharge of activity for 174 patients (202 treatments) undergoing treatment of thyroid carcinoma with radioactive iodine. We have found that approximately 55% of administered activity is excreted in the first 24 h and that 85% of administered activity is discharged to the sewer over a typical inpatient stay of 5 days. There was no significant difference in levels of discharge between those patients undergoing inaugural ablation therapy and those having further treatments with radioactive iodine.

Direct-to-consumer drug marketing: public service or disservice?

Pharmaceutical industry spending on direct-to-consumer advertising has been increasing rapidly. While the primary goal of direct-to-consumer advertising is to sell drugs, supposed secondary goals include patient education and improved health. However, these benefits of direct-to-consumer advertising are unproved. Moreover, such advertising may create unnecessary tension between the patient and the patient's physician and insurer, and may divert physicians' efforts away from important patient concerns, and toward marketing-generated discussions. On the other hand, direct-to-consumer advertising may lead to patient-doctor encounters that would not have occurred otherwise. Direct-to-consumer advertising should be modified to unambiguously benefit the health-care interests of consumers and patients.

Expertise and the perception of kinematic and situational probability information.

Two experiments were conducted on the nature of expert perception in the sport of squash. In the first experiment, ten expert and fifteen novice players attempted to predict the direction and force of squash strokes from either a film display (occluded at variable time periods before and after the opposing player had struck the ball) or a matched point-light display (containing only the basic kinematic features of the opponent's movement pattern). Experts out-performed the novices under both display conditions, and the same basic time windows that characterised expert and novice pick-up of information in the film task also persisted in the point-light task. This suggests that the experts' perceptual advantage is directly related to their superior pick-up of essential kinematic information. In the second experiment, the vision of six expert and six less skilled players was occluded by remotely triggered liquid-crystal spectacles at quasi-random intervals during simulated match play. Players were required to complete their current stroke even when the display was occluded and their prediction performance was assessed with respect to whether they moved to the correct half of the court to match the direction and depth of the opponent's stroke. Consistent with experiment 1, experts were found to be superior in their advance pick-up of both directional and depth information when the display was occluded during the opponent's hitting action. However, experts also remained better than chance, and clearly superior to less skilled players, in their prediction performance under conditions where occlusion occurred before any significant pre-contact preparatory movement by the opposing player was visible. This additional source of expert superiority is attributable to their superior attunement to the information contained in the situational probabilities and sequential dependences within their opponent's pattern of play.

The glycaemic index of a range of gluten-free foods.

AIMS: The number of people with both diabetes and coeliac disease is increasing. This study examined the effect of gluten-free, as opposed to gluten-replete carbohydrate containing foods, on post-prandial blood glucose concentrations. METHODS: The glycaemic index of six commonly used gluten-free carbohydrates are reported and compared with published figures for similar non-gluten-free products. RESULTS: The results indicate that the glycaemic index of gluten-free and gluten containing foods are similar. CONCLUSIONS: The inclusion of gluten-free foods in the diet of diabetic individuals with coeliac disease should not compromise glycaemic control.

Inactivation of Proteolytic Enzymes from Porphyromonas gingivalis Using Light-activated Agents.

Previous studies have shown one of the causative agents of periodontitis, Porphyromonas gingivalis, can be killed by red light in the presence of the light-activated antimicrobial agent toluidine blue O (TBO). The purpose of this study was to determine the effects of irradiating the organism with red light in the presence of TBO on its proteolytic enzyme activity.Suspensions of P. gingivalis were exposed to light with a wavelength of 633 nm in the presence of various concentrations of TBO. Samples were taken at various times and their proteolytic activity determined by assay of azocasein hydrolysis. On exposure to 126 J of red light in the presence of 12.5 µg/ml of TBO the proteolytic enzyme activity was reduced by 100%.The results of this study have shown that the main virulence factor of P. gingivalis, its proteolytic activity, can be inactivated by red light in the presence of TBO. This, together with the known bactericidal activity of the TBO/light combination, suggests that photodynamic therapy may prove important in reducing the effectiveness of P. gingivalis as a periodontopathogen in vivo.

Prevalence and persistence of amoxycillin-resistant bacteria in the dental plaques of adults.

The prevalence and persistence of amoxycillin-resistant organisms (ARO) in the dental plaque of adults was determined. Plaque samples from ten adults, who had not taken antibiotics during the previous 6 months, were screened for ARO on three occasions at intervals of 3 months. The ARO were tested for their susceptibility to amoxycillin and to amoxycillin plus clavulanic acid as well as their ability to produce beta-lactamases. The ARO were found in all subjects on at least one sampling occasion and in 87% of the 30 samples examined. Of the 36 ARO isolated, 33% were yeasts, 19% were staphylococci, 19% Actinomycetes spp. and 14% lactobacilli, whilst seventeen of the isolates produced a beta-lactamase and seven of these were sensitive to coamoxiclav. The proportion of ARO in an individual fluctuated widely over the study period. It is suggested that the ARO are frequently, though transiently, present in low numbers in the plaque of individuals who have not recently received antibiotics.

Jewish mystical movements and the European ergot epidemics.

Chronic intake of ergot, a chemical present in bread blighted by ergot-producing fungi, results in a wide variety of neuropsychiatric and vascular symptoms. The symptomatology and epidemiology of outbreaks of ergot poisoning are traced, and are shown to coincide with the emergence of Jewish mystical movements, such as the early Pietist movement in Germany, Sabbateanism and Chasidism, thus suggesting that environmental ergotism contributed to these mystical movements. The interaction between ergotism and other nutritional, neuropsychiatric, social, psychological and historical influences is considered.

Clinical outcomes of the Otago-Southland Breast Cancer Screening Programme 1991-1996.

AIM: To document the clinical outcome of the Otago-Southland Breast Cancer Screening Programme through its first two rounds of screening, from 1991-1996. METHODS: Review and analysis of clinical and pathological records. RESULTS: In the first round of screening, 13,876 women were screened, giving 75% uptake; 12.2% were referred for assessment and 126 cancers detected, 9.1 per thousand women screened. For the 9946 incidence screens in the second round, 3.9% of women screened were referred to assessment and 50 cancers detected, 5.0 per thousand women screened. The uptake and cancer detection rates exceed the targets and exceed other published results; the size distribution of the cancers detected was comparable to the Swedish two-counties study, showing that the results should produce an ultimate mortality reduction. The referral rate to assessment was higher than expected in the first round of screening, but within the targeted range in the second round. The benign to malignant ratio for all biopsies was 1.4:1 for the prevalence screen of the first round and 1.2:1 for the incidence screens in the second round, both exceeding the targets set. CONCLUSIONS: The results show that the uptake and clinical results of the programme exceed expectations and that a large number of small invasive tumours have been successfully detected. These results are comparable to the best of overseas studies, and give confidence that mortality reductions will ultimately occur.

A Ras-dependent pathway regulates RNA polymerase II phosphorylation in cardiac myocytes: implications for cardiac hypertrophy.

Despite extensive evidence implicating Ras in cardiac muscle hypertrophy, the mechanisms involved are unclear. We previously reported that Ras, through an effector-like function of Ras GTPase-activating protein (GAP) in neonatal cardiac myocytes (M. Abdellatif et al., J. Biol. Chem. 269:15423-15426, 1994; M. Abdellatif and M. D. Schneider, J. Biol. Chem. 272:527-533, 1997), can up-regulate expression from a comprehensive set of promoters, including both cardiac cell-specific and constitutive ones. To investigate the mechanism(s) underlying these earlier findings, we have used recombinant adenoviruses harboring a dominant negative Ras (17N Ras) allele or the N-terminal domain of GAP (nGAP), responsible for the Ras-like effector function. Inhibition of endogenous Ras reduced basal levels of [3H]uridine and [3H]phenylalanine incorporation into total RNA, mRNA, and protein, with parallel changes in apparent cell size. In addition, 17N Ras markedly inhibited phosphorylation of the C-terminal domain (CTD) of RNA polymerase II (pol II), known to regulate transcript elongation, accompanied by down-regulation of its principal kinase, cyclin-dependent kinase 7 (Cdk7). In contrast, nGAP elicited the opposite effects on each of these parameters. Furthermore, cotransfection of constitutively active Ras (12R Ras) with wild-type pol II, rather than a truncated mutant lacking the CTD, demonstrated that Ras activation of transcription was dependent on the pol II CTD. Consistent with a potential role for this pathway in the development of cardiac myocyte hypertrophy, alpha1-adrenergic stimulation similarly enhanced pol II phosphorylation and Cdk7 expression, where both effects were inhibited by dominant negative Ras, while pressure overload hypertrophy led to an increase in both hyperphosphorylated and hypophosphorylated pol II in addition to Cdk7.

Breast cancer in women who undergo screening mammography: relationship of hormone replacement therapy to stage and detection method.

PURPOSE: To compare the breast cancer stages and detection methods in screened women who receive hormone replacement therapy (HRT) with those in screened women who do not receive HRT to determine whether HRT affects the stage or mammographic detection of malignancy. MATERIALS AND METHODS: One hundred fifteen cases of breast cancer in women (age range, 55-65 years) in whom at least one screening mammogram had been obtained at least 24 months before diagnosis and in whom the history regarding HRT could be determined were reviewed retrospectively. Statistical analysis was performed with CHI-2 analysis and the Fischer exact test. RESULTS: The cancer stages in the 58 women who received HRT were stage 0 in 15 (26%), stage I in 28 (48%), stage II in 13 (22%), and stage III in two (3%) women. The stages in the 57 women who did not receive HRT were stage 0 in 19 (33%), stage I in 24 (42%), stage II in 11 (19%), stage III in two (4%), and stage IV in one (2%) woman. Cancers in 38 (67%) of the women who did not receive HRT and in 38 (66%) of those who did receive HRT were detected with mammography alone; false-negative mammograms were obtained in five (9%) women in the non-HRT group and in four (7%) women in the HRT group (P = .89). CONCLUSION: Among screened women who developed breast cancer, there were no significant differences in cancer stages or in the number of mammographically detected cancers or false-negative mammograms between the HRT group and the non-HRT group.

Venous endothelial changes in therapeutic arteriovenous fistulae.

Specimens of veins of therapeutic arteriovenous fistulae from five patients were examined by an en face immunohistochemical technique to investigate endothelial morphology and the presence of the vasoactive peptide endothelin-1 (ET-1). These were compared with control segments of long saphenous veins from six patients. Venous endothelium from the arteriovenous shunts was mostly intact even overlying phlebosclerotic plaques. Occasional small areas of denudation, with associated platelets, were present in the depressions of 'jet' lesion however. The endothelial cells were generally elongated and interspersed with foci of polyhedral cells. The control saphenous veins contained elongated endothelial cells without detectable denudation. Image analysis of histological sections of veins from the shunts indicated significantly less intact elastic tissue than control veins but greater mononucleated endothelial cell density in en face preparations. ET-1 staining was considerably stronger in endothelium from the fistulae than in the control saphenous veins and was most intense over the raised crescentic ridges of jet lesions, stenoses and phlebosclerotic plaques. Endothelial mitoses and cells with hyperchromatic nuclei stained more strongly for ET-1 than surrounding cells. These results indicate that the endothelial cells lining veins associated with arteriovenous fistulae are dynamically altered by the increased haemodynamic stresses associated with these shunts. Furthermore ET-1 may act as a localising factor associated with intimal thickening at sites of 'jet' lesions, stenosis and phlebosclerosis.