Reduced lactate dehydrogenase activity in the heart and suppressed sex hormone levels are associated with female-biased mortality during thermal stress in Pacific salmon.

Female-biased mortality has been repeatedly reported in Pacific salmon during their upriver migration in both field studies and laboratory holding experiments, especially in the presence of multiple environmental stressors, including thermal stress. Here, we used coho salmon (Oncorhynchus kisutch) to test whether females exposed to elevated water temperatures (18°C) (i) suppress circulating sex hormones (testosterone, 11-ketotestosterone and estradiol), owing to elevated cortisol levels, (ii) have higher activities of enzymes supporting anaerobic metabolism (e.g. lactate dehydrogenase, LDH), (iii) have lower activities of enzymes driving oxidative metabolism (e.g. citrate synthase, CS) in skeletal and cardiac muscle, and (iv) have more oxidative stress damage and reduced capacity for antioxidant defense [lower catalase (CAT) activity]. We found no evidence that a higher susceptibility to oxidative stress contributes to female-biased mortality at warm temperatures. We did, however, find that females had significantly lower cardiac LDH and that 18°C significantly reduced plasma levels of testosterone and estradiol, especially in females. We also found that relative gonad size was significantly lower in the 18°C treatment regardless of sex, whereas relative liver size was significantly lower in females held at 18°C. Further, relative spleen size was significantly elevated in the 18°C treatments across both sexes, with larger warm-induced increases in females. Our results suggest that males may better tolerate bouts of cardiac hypoxia at high temperature, and that thermal stress may also disrupt testosterone- and estradiol-mediated protein catabolism, and the immune response (larger spleens), in migratory female salmon.

Tissue diagnosis during colorectal cancer surgery using optical sensing: an in vivo study.

BACKGROUND: In colorectal cancer surgery there is a delicate balance between complete removal of the tumor and sparing as much healthy tissue as possible. Especially in rectal cancer, intraoperative tissue recognition could be of great benefit in preventing positive resection margins and sparing as much healthy tissue as possible. To better guide the surgeon, we evaluated the accuracy of diffuse reflectance spectroscopy (DRS) for tissue characterization during colorectal cancer surgery and determined the added value of DRS when compared to clinical judgement. METHODS: DRS spectra were obtained from fat, healthy colorectal wall and tumor tissue during colorectal cancer surgery and results were compared to histopathology examination of the measurement locations. All spectra were first normalized at 800 nm, thereafter two support vector machines (SVM) were trained using a tenfold cross-validation. With the first SVM fat was separated from healthy colorectal wall and tumor tissue, the second SVM distinguished healthy colorectal wall from tumor tissue. RESULTS: Patients were included based on preoperative imaging, indicating advanced local stage colorectal cancer. Based on the measurement results of 32 patients, the classification resulted in a mean accuracy for fat, healthy colorectal wall and tumor of 0.92, 0.89 and 0.95 respectively. If the classification threshold was adjusted such that no false negatives were allowed, the percentage of false positive measurement locations by DRS was 25% compared to 69% by clinical judgement. CONCLUSION: This study shows the potential of DRS for the use of tissue classification during colorectal cancer surgery. Especially the low false positive rate obtained for a false negative rate of zero shows the added value for the surgeons. Trail registration This trail was performed under approval from the internal review board committee (Dutch Trail Register NTR5315), registered on 04/13/2015, https://www.trialregister.nl/trial/5175 .

Fat/water ratios measured with diffuse reflectance spectroscopy to detect breast tumor boundaries.

Recognition of the tumor during breast-conserving surgery (BCS) can be very difficult and currently a robust method of margin assessment for the surgical setting is not available. As a result, tumor-positive margins, which require additional treatment, are not found until histopathologic evaluation. With diffuse reflectance spectroscopy (DRS), tissue can be characterized during surgery based on optical parameters that are related to the tissue morphology and composition. Here we investigate which optical parameters are able to detect tumor in an area with a mixture of benign and tumor tissue and hence which parameters are most suitable for intra-operative margin assessment. DRS spectra (400-1600 nm) were obtained from 16 ex vivo lumpectomy specimens from benign, tumor border, and tumor tissue. One mastectomy specimen was used with a custom-made grid for validation purposes. The optical parameter related to the absorption of fat and water (F/W-ratio) in the extended near-infrared wavelength region (~1000-1600 nm) provided the best discrimination between benign and tumor sites resulting in a sensitivity and specificity of 100 % (excluding the border sites). Per patient, the scaled F/W-ratio gradually decreased from grossly benign tissue towards the tumor in 87.5 % of the specimens. In one test case, based on a predefined F/W-ratio for boundary tissue of 0.58, DRS produced a surgical resection plane that nearly overlapped with a 2-mm rim of benign tissue, 2 mm being the most widely accepted definition of a negative margin. The F/W-ratio provided excellent discrimination between sites clearly inside or outside the tumor and was able to detect the border of the tumor in one test case. This work shows the potential for DRS to guide the surgeon during BCS.

Differentiation of healthy and malignant tissue in colon cancer patients using optical spectroscopy: A tool for image-guided surgery.

BACKGROUND: Surgery for colorectal cancer aims for complete tumor resection. Optical-based techniques can identify tumor and surrounding tissue through the tissue specific optical properties, absorption and scattering, which are both influenced by the biochemical and morphological composition of the tissue. OBJECTIVE: To evaluate the feasibility of dual-modality Diffuse Reflectance Spectroscopy-Fluorescence Spectroscopy (DRS-FS) for discrimination between healthy and malignant tissue in colorectal surgery. METHODS: Surgical specimens from colorectal cancer patients were measured immediately after resection using a fiber-optic needle capable of dual-modality DRS-FS. Model-based analyses were used to derive scattering and absorption coefficients and intrinsic fluorescence. Volume fractions of chromophores were estimated. Furthermore, optical data were recorded along a trajectory from healthy tissue towards tumor. RESULTS: Spectral characteristics were identified in 1,273 measured spectra from 21 specimens. Combined DRS and FS discriminated tumor from surrounding tissue with a sensitivity of 95% and a specificity of 88%. Significant spectral changes were seen along the trajectory from healthy tissue to tumor. CONCLUSION: This study demonstrates that dual-modality DRS-FS can identify colorectal cancer from surrounding healthy tissue. The quantification of comprehensible parameters allows robust classification and facilitates extrapolation towards the clinical setting. The technique, here demonstrated in a needle like probe, can be incorporated into surgical tools for optically guided surgery in the near future. Lasers Surg. Med. 47:559-565, 2015. © 2015 Wiley Periodicals, Inc.

Corrigendum to: Sex-specific differences in swimming, aerobic metabolism and recovery from exercise in adult coho salmon (Oncorhynchus kisutch) across ecologically relevant temperatures.

[This corrects the article DOI: 10.1093/conphys/coab016.].

Sex-specific differences in swimming, aerobic metabolism and recovery from exercise in adult coho salmon (Oncorhynchus kisutch) across ecologically relevant temperatures.

Adult female Pacific salmon can have higher migration mortality rates than males, particularly at warm temperatures. However, the mechanisms underlying this phenomenon remain a mystery. Given the importance of swimming energetics on fitness, we measured critical swim speed, swimming metabolism, cost of transport, aerobic scope (absolute and factorial) and exercise recovery in adult female and male coho salmon (Oncorhynchus kisutch) held for 2 days at 3 environmentally relevant temperatures (9°C, 14°C, 18°C) in fresh water. Critical swimming performance (U crit) was equivalent between sexes and maximal at 14°C. Absolute aerobic scope was sex- and temperature-independent, whereas factorial aerobic scope decreased with increasing temperature in both sexes. The full cost of recovery from exhaustive exercise (excess post-exercise oxygen consumption) was higher in males compared to females. Immediately following exhaustive exercise (i.e. 1 h), recovery was impaired at 18°C for both sexes. At an intermediate time scale (i.e. 5 h), recovery in males was compromised at 14°C and 18°C compared to females. Overall, swimming, aerobic metabolism, and recovery energetics do not appear to explain the phenomenon of increased mortality rates in female coho salmon. However, our results suggest that warming temperatures compromise recovery following exhaustive exercise in both male and female salmon, which may delay migration progression and could contribute to en route mortality.

[Cross-allergy to penicillins and cephalosporins: problematic when prescribing cephalosporins?] / Kruisallergie van penicillines met cefalosporines.

Penicillin allergy is commonly reported and often influences selection of antimicrobial treatment. Due to concerns about cross-allergic reactions, other beta-lactams - particularly cephalosporins - may also be avoided. This too often results in less effective treatment, more side effects and overconsumption of reserve antimicrobial agents. Most patients (> 90%) with a penicillin allergy label are not truly allergic, i.e., they do not have an 'immediate type' (IgE-mediated) allergy when tested. Based on current data, even in patients with a true penicillin allergy, the risk of severe cross-allergic reactions to cephalosporins is very low. Clinicians tend to overestimate this risk: this dilemma can be resolved with a systematic appraisal of risk probabilities. The limited risk of a true penicillin allergy being present and the subsequent low risk of a cross-allergic reaction to cephalosporins generally outweighs the disadvantages of selecting an alternative (non-beta-lactam) antimicrobial regimen.

Personalization of CM Injection Protocols in Coronary Computed Tomographic Angiography (People CT Trial).

Aim: To evaluate the performance of three contrast media (CM) injection protocols for cardiac computed tomography angiography (CCTA) based on body weight (BW), lean BW (LBW), and cardiac output (CO). Materials and methods. A total of 327 consecutive patients referred for CCTA were randomized into one of the three CM injection protocols, where CM injection was based on either BW (112 patients), LBW (108 patients), or CO (107 patients). LBW and CO were calculated via formulas. All scans were ECG-gated and performed on a third-generation dual-source CT with 70-120 kV (automated tube voltage selection) and 100 kVqual.ref/330 mAsqual.ref. CM injection protocols were also adapted to scan time and tube voltage. The primary outcome was the proportion of patients with optimal intravascular attenuation (325-500 HU). Secondary outcomes were mean and standard deviation of intravascular attenuation values (HU), contrast-to-noise ratio (CNR), and subjective image quality with a 4-point Likert scale (1 = poor/2 = sufficient/3 = good/4 = excellent). The t-test for independent samples was used for pairwise comparisons between groups, and a chi-square test (χ2) was used to compare categorical variables between groups. All p values were 2-sided, and a p < 0.05 was considered statistically significant. Results: Mean overall HU and CNR were 423 ± 60HU/14 ± 3 (BW), 404 ± 62HU/14 ± 3 (LBW), and 413 ± 63HU/14 ± 3 (CO) with a significant difference between groups BW and LBW (p=0.024). The proportion of patients with optimal intravascular attenuation (325-500 HU) was 83.9%, 84.3%, and 86.9% for groups BW, LBW, and CO, respectively, and between-group differences were small and nonsignificant. Mean CNR was diagnostic (≥10) in all groups. The proportion of scans with good-excellent image quality was 94.6%, 86.1%, and 90.7% in the BW, LBW, and CO groups, respectively. The difference between proportions was significant between the BW and LBW groups. Conclusion: Personalization of CM injection protocols based on BW, LBW, and CO, and scan time and tube voltage in CCTA resulted in low variation between patients in terms of intravascular attenuation and a high proportion of scans with an optimal intravascular attenuation. The results suggest that personalized CM injection protocols based on LBW or CO have no additional benefit when compared with CM injection protocols based on BW.

The performance of non-ECG gated chest CT for cardiac assessment - The cardiac pathologies in chest CT (CaPaCT) study.

PURPOSE: Evaluating the prevalence of CAD on non-ECG gated chest CTs, image quality (IQ) and the clinical performance of the CAD-RADS classification for predicting cardiovascular events (CVE). METHODS: 215 consecutive patients referred for chest CTs between May 2016 and March 2018 were included (3rd-generation DSCT) using non-ECG gated acquisitions with automated tube voltage selection (110kVqual.ref/40mAsqual.ref), pitch 2.65-3.0 and individualized contrast media injection protocols. Dedicated cardiac post-processing reconstructions (0.6 mm/0.4 mm/Kernel Bv36) were added to standard chest reconstructions. Two independent cardiac radiologists performed a 3-step analysis. In case of discrepancy, a third reader gave the final decision. Step 1: visual presence of calcifications; 2: scans with calcifications assessed for IQ using a 5-point Likert scale (poor/sufficient/moderate/good/excellent); 3: stenosis severity was analysed in detail (if Likert sufficient-excellent using CAD-RADS). Electronic patient files were checked to see if pathology was previously mentioned (incidental) and whether patients developed an CVE during follow-up. RESULTS: 1: Calcifications were present in 156/215 cases (72.6 %), 74 of these were incidental. 2: In 68/156 (43.6 %) patients with calcifications IQ was rated sufficient-excellent. 3: CAD-RADS≥3 was seen in 39/68 patients (57.4 %), 12 times (30.8 %) findings were incidental. During follow-up (median 16 [0-35] months), 7/39 (18 %) patients with CAD-RADS≥3 developed a CVE. 17 patients died during follow-up. CONCLUSION: Coronary calcification on non ECG-gated chest CTs was detected in 72.6 % of patients, cardiac assessment was feasible in nearly half of these patients. Only patients with a CAD-RADS≥3 developed CVE, therefore the CAD-RADS may help identify and guide patients at risk of future CVE.

Acetic acid as a decontamination method for ICU sink drains colonized by carbapenemase-producing Enterobacteriaceae and its effect on CPE infections.

BACKGROUND: Carbapenemase-producing Enterobacteriaceae (CPE) are emerging pathogens representing a major concern for public health. In Belgium, the OXA-48 carbapenemase resistance gene is identified most frequently. Sink drains in intensive care units (ICUs) are known to be colonized by Gram-negative bacilli. A correlation between environmental contamination and CPE infections in ICUs has been established. A long-term CPE epidemic in a local ICU proved difficult to control. METHODS AND RESULTS: A variety of CPE strains, all carrying the OXA-48 resistance gene, were isolated from almost all sinks in patient rooms in the ICU. Decontamination of the sinks with 250 mL 25% acetic acid three times weekly was implemented. Sink drain colonization was followed up for six months thereafter. Both the number of CPE-colonized sinks and the number of patients colonized or infected with CPE decreased drastically, to the extent that the epidemic was considered to be eradicated. In-vitro growth of all isolates was inhibited by a concentration of acetic acid equal to or smaller than that used for decontamination. Epidemiological analysis demonstrated a positive and significant relationship between contaminated sinks and CPE acquisition of patients admitted to ICU rooms, indicating the importance of contaminated sinks as the environmental reservoir of the epidemic. CONCLUSION: Decontamination of sink drains with acetic acid is a valuable alternative to other methods, such as heated sinks and water-free care, especially when other options are not feasible in the short term. Acetic acid is cheap, widely available, effective and manageable from a safety and technical point of view.

A cluster of hepatitis B infections associated with incorrect use of a capillary blood sampling device in a nursing home in the Netherlands, 2007.

In July 2007, two residents of a nursing home were diagnosed with acute Hepatitis B virus infection. To identify risk factors for HBV infection a retrospective cohort study among residents was performed. Case finding included discharged diabetes patients and those receiving home care. Among 32 residents one case of chronic hepatitis B was found that could be identified by genotyping as the source patient for the acute cases. Diabetes and finger sticks were risk factors for HBV infection. Most likely the cause of transmission was a multiclix finger stick device developed for use in individual patients but used in multiple patients. Education and training in the use of new equipment and hygiene audits remain the cornerstones in infection control practices.

Synergistic antitumor effects of rat gamma-interferon and human tumor necrosis factor alpha against androgen-dependent and -independent rat prostatic tumors.

We have examined the antitumor effects of rat gamma-interferon (IFN-gamma) and human tumor necrosis factor alpha (TNF) against androgen-dependent and -independent Dunning rat prostatic tumors. In vitro studies, using the double layer soft agar assay, showed a very limited antiproliferative activity of the drugs in the dose range tested (1-1000 units IFN-gamma and/or 1-1000 ng TNF/dish). For in vivo studies IFN-gamma and TNF were administered s.c., peritumorally. IFN-gamma was given 3 times/week, 8,000 or 80,000 units/rat, and TNF 5 times/week, 10 or 100 micrograms/rat. IFN-gamma and TNF monotherapy were not significantly effective in inhibiting tumor growth, except for IFN-gamma against the androgen-independent MatLyLu tumor. Combinations of IFN-gamma and TNF had synergistic antiproliferative effects against all four tumor lines tested; however, complete growth inhibitions could not be achieved. Survival studies showed significant increase in survival of tumor-bearing rats.

Real-time in vivo assessment of radiofrequency ablation of human colorectal liver metastases using diffuse reflectance spectroscopy.

BACKGROUND: The success of radiofrequency (RF) ablation is limited by the inability to assess thermal tissue damage achieved during or immediately after the procedure. The goal of this proof-of-principle study was to investigate whether diffuse reflectance (DR) spectroscopy during and after RF ablation of liver tumours could aid in detecting complete tissue ablation. MATERIAL AND METHODS: DR spectra were acquired in vivo in eight patients undergoing RF ablation for unresectable colorectal liver metastases, using a disposable spectroscopy needle. Intraoperative ultrasound imaging was used for accurate positioning of the RF electrode and the spectroscopy needle. Spectral changes were quantified and correlated to tissue histopathology and follow-up CT imaging. RESULTS: For the lesions in which ablation was monitored by DR spectroscopy (N = 8), median tumour size was 1.6 cm (range 0.8-3.3 cm). We found an excellent correlation (97-99%) between thermal damage suggested by spectral changes and histology. DR spectroscopy allowed discrimination between non-ablated and ablated tissue, regardless whether the needle was placed in tumour tissue or in surrounding liver tissue. Additional measurements performed continuously during ablation confirmed that the magnitude of spectral change correlates with the histochemical degree of thermal damage. CONCLUSIONS: Diffuse reflectance spectroscopy allows accurate quantification of thermal tissue damage during and after RF ablation. Real-time feedback by DR spectroscopy could improve the accuracy and quality of the RF procedures by lowering incomplete ablation rates.

Rapid emergence of resistant coagulase-negative staphylococci on the skin after antibiotic prophylaxis.

One approach for prosthetic vascular surgery is to continue antimicrobial prophylaxis while intravascular lines and catheters are in place. However this may give rise to antimicrobial resistance in the colonizing bacterial flora. We studied 37 patients undergoing vascular surgery, who received either co-amoxyclav for three days (group 1), ofloxacin plus metronidazole for three days (group 2) or for one day (group 3), respectively. Seventeen hospitalized patients not undergoing surgery or receiving antibiotics were studied as controls. In groups I and II there was a significant decline in susceptibility to cloxacillin (12.8% respectively 23.6%) and ofloxacin (0.5% and 85% respectively) in skin staphylococci. The results from group 3 were intermediate. Molecular typing showed that the patient's susceptible community-derived strains were replaced by genetically unrelated resistant strains, probably hospital derived. Long-term prophylaxis should be avoided as colonization occurs with resistant strains.

Multidisciplinary evaluation of rat renal cell carcinoma.

The rat renal cell carcinoma system as described by deVere White and Olsson in 1980 is used widely as a model for its human counterpart. The tumor arose spontaneously in a male Wistar Lewis rat and its behaviour has been shown to be stable during multiple passages. We have compared this tumor with the human renal cell carcinoma using a multidisciplinary approach. Light microscopy and electron microscopy showed a great resemblance of this rat tumor to a human renal cell carcinoma of the clear cell type with the ultrastructural presence of desmosomes. With the use of tissue specific antibodies against intermediate filament proteins, it could be shown that their expression is comparable to human renal cell carcinoma, i.e. coexpression of vimentin and different cytokeratins in the tumor cells. The cells could also be shown to contain cytokeratin 18. An aneuploid cell population in the tumor, expressing both vimentin and keratin, could be characterized by DNA flow cytometry in double labeling experiments. Comparison of normal and malignant rat kidney tissue by Northern blot analysis revealed increased levels of vimentin mRNA. In conclusion, this tumor model seems to have several histological and biological properties in common with the human renal tumor.

Multiparameter analysis of four human renal cell carcinoma xenografts in nude mice.

Four human renal cell carcinoma xenografts (RC2, RC14, RC43, NC65), maintained in nude mice for several years, were investigated in a multi - disciplinary study, using (immuno) histochemical, biochemical and ultrastructural techniques. Histological, cellular, nuclear and biological characteristics were investigated. All tumors showed histologically recognizable features of human renal cell carcinomas, although marked differences between the four tumors were seen, both at the histological and ultrastructural level. Flowcytometric analysis of tumor cell suspensions allowed DNA quantification as well as the detection of subpopulations. Immunohistochemical staining procedures using tissue specific antibodies against intermediate filament proteins revealed two populations of tumor cells. Most tumor cells in three of the xenografts coexpressed cytokeratins and vimentin, while in RC43 most of the tumor cells expressed only vimentin. Northern blot analysis showed a higher expression of vimentin mRNA in all tumors as compared to normal kidney tissue. RC43 showed a three-fold higher level of vimentin mRNA than the other xenografts. Growth potential in the human tumor cloning system was evaluated by temporal growth pattern analysis. These experiments showed that the xenografts resemble human primary renal cell tumors in different ways, and reflect different characteristics that can be present in human renal cell carcinoma.

Semi-automated database design by the end-user.

An information system was developed to manage the data for a large number of research projects simultaneously. The system, called URIS, has facilitated the management of research data in an academic urological department. It enables end-users, who are not necessarily skilled computer scientists, to design their own databases semi-automatically, by supporting data entry screen design and the specification of research items. The system creates the database tables automatically after these activities. The specification of research items is the most important but also most difficult part in this process.

[The treatment of kidney and ureteral stones using a second-generation kidney stone lithotriptor]. / De behandeling van nier- en ureterstenen met een niersteenvergruizer van de tweede generatie.

In January 1988 a Siemens Lithostar lithotriptor was installed in the Radboud University Hospital in Nijmegen. Over 1600 treatments have been performed since. The results of 582 treatments of the first 500 patients are discussed. After three months 51.3% of the patients were free of stones. After six months this percentage was 64.5 and in addition 25.4% of the patients were free of symptoms although residual particles were still present. In only 10.1% of the patients did the ESWL treatment not succeed. In over 50% of the cases treatment was performed on an outpatient basis. Among 90% of the patients in whom treatment was performed without auxiliary procedures only 50% needed i.v. sedation or analgesia. The other 50% did not need any form of sedation or analgesia. Major complications did not occur although 376 patients (75.2%) suffered from a short period of haematuria and many patients had a skin lesion. With the possibility of outpatient treatment, the use of less anaesthesia and a success rate of 89.9% (residual stones, less than 5 mm in diameter, which can be evacuated spontaneously) after six months, the Lithostar is an improvement in the treatment of urolithiasis.

Optical sensing for tumor detection in the liver.

BACKGROUND: There is an increasing trend for optical guidance techniques in surgery. Optical imaging using Diffuse Reflectance Spectroscopy (DRS) can distinguish different tissue types through a specific "optical fingerprint". We investigated whether DRS could discriminate metastatic tumor tissue from normal liver tissue and thus if this technique would have potential for further implementation into surgical instruments or radiological intervention tools. METHODS: A miniaturized optical needle was developed able to collect DRS spectra between 500 and 1600 nm. Liver specimen of 24 patients operated for colorectal liver metastases were analyzed with DRS immediately after resection. Multiple measurements were performed and DRS results were compared to the histology analysis of the measurement locations. In addition, normal liver tissue was scored for the presence or absence of steatosis. RESULTS: A total of 780 out of the 828 optical measurements were correctly classified into either normal or tumor tissue. The resulting sensitivity and specificity were both 94%. The results of the analysis for each patient individually showed an accuracy of 100%. The Spearman's rank correlation of DRS-estimated percentages of hepatic steatosis in liver tissue compared to that of the pathologist was 0.86. CONCLUSIONS: DRS demonstrates a high accuracy in discriminating normal liver tissue from colorectal liver metastases. DRS can also predict the degree of hepatic steatosis with high accuracy. The technique, here demonstrated in a needle like probe, may as such be incorporated into surgical tools for optical guided surgery or percutaneous needles for radiological interventions.