Hyperthermic intraperitoneal chemotherapy (HIPEC) and cytoreductive surgery (CS) as treatment of peritoneal carcinomatosis: preliminary results in Croatia

The purpose of our study was to evaluate initial results following introduction of Hyperthermic Intraperitoneal Chemotherapy (HIPEC) and Cytoreductive Surgery (CS). Twenty two patients with intraperitoneal malignancy undergone cytoreductive surgery (CS) and hyperthermic intraoperative chemotherapy (HIPEC) between January of 2007 and January 2010. Nine patients had adenocarcinoma of colorectal origin, 8 patients had ovarian cancer, and 5 had pseudomyxoma peritonei. Inclusion criteria were diagnosis of peritoneal carcinomatosis based on intraoperative assessment during first operative procedure for intraabdominal malignancy or follow-up diagnostic imaging proof Excluded were patients with known malignant proliferation outside abdomen, liver metastasis and ASA score 4 and higher. All patients with pseudomyxoma peritonei diagnosis are alive, with mean follow-up time 24.8 months (range 15-35). In group of patients with adenocarcinoma from colorectal origin, 3 died, resulting in mean survival time 7.6 months (range 1-16). In group of patients with ovarian cancer, 2 died, resulting in mean survival time 13.8 months (range 0-31). Two patients died in early postoperative period. Most of the patients had some sort of mental disorder. Although HIPEC with CS improves survival, during introduction period higher morbidity and mortality could be expected.     

Time-course expression of metallothioneins and tissue metals in chronic relapsing form of experimental autoimmune encephalomyelitis

To elucidate the role of metallothioneins (MTs) in the pathomechanisms of autoimmune CNS disorders we estimated the expression of MTs I+II and the tissue concentrations of Zn2+ and Cu2+ in the brain, spinal cord (SC) and in the liver during the periods of attacks and remissions in chronic relapsing experimental autoimmune encephalomyelitis (CR-EAE). Disease was induced in the genetically susceptible Dark Agouti (DA) rats by subcutaneous injection of bovine brain homogenate in CFA. Control rats were treated with CFA. The data, obtained by clinical assessment, immunohistochemistry and inductivity coupled plasma spectrometry, have shown that during the first attack (on the 12th day) MTs I+II were markedly upregulated in subarachnoid regions and perivascular space on astrocytes, microglia and on spinal neurons. Simultaneously, the concentrations of zinc in the SC and zinc and copper in the liver have found to be increased. During the second attack (on the 22nd day) a new overexpression of MTs was found in the cerebellum, in sulcus hippocampi, in spinal neurons and particularly in hepatocytes around the central vein. Concomitantly, in the brain and SC the concentration of copper increased. The data point to a neuroprotective role of MTs and to an important regulatory role of essential metals and hepatic MTs in the pathogenesis of CR-EAE.     

Dual antiplatelet therapy in patients with aspirin resistance following coronary artery bypass grafting: study protocol for a randomized controlled trial [NCT01159639

ABSTRACT: BACKGROUND: Coronary artery disease remains the dominant cause of mortality in developed countries. While platelets have been recognized to play a pivotal role in atherothrombosis, the ideal antiplatelet regime after coronary artery surgery remains elusive.The evolution of CABG has presently moved beyond technical improvements to involve modulation of pharmacologic management designed to improve patient outcomes. The aim of this trial will be to test the hypothesis that the addition of clopidogrel to patients with documented postoperative aspirin resistance will reduce the incidence of major cardiovascular events. METHODS: Patients scheduled for isolated coronary artery surgery will be eligible for the study. Patients in whom postoperative multiple electrode aggregometry documents aspirin resistance will be randomized into two groups. The control group will receive 300 mg of aspirin. The dual antiplatelet group will receive 75 mg of clopidogrel in addition to 300 mg of aspirin. Patients will be followed for 6 months. Major adverse cardiac and cerebrovascular events (death from any cause, myocardial infarction, stroke, hospitalization due to cardiovascular pathology) as well as bleeding events will be recorded. DISCUSSION: This will be the first trial that will specifically address the issue of dual antiplatelet therapy in patients undergoing coronary artery surgery who have been found to be aspirin resistant. In the event that the addition of clopidogrel proves to be beneficial in this subset of surgical patients, this study could significantly impact their future antiplatelet management.This randomized controlled trial has been registered at the ClinicalTrials.gov website (Identifier NCT01159639).     

Skin histology and its role in heat dissipation in three pinniped species

ABSTRACT: BACKGROUND: Pinnipeds have a thick blubber layer and may have difficulty maintaining their body temperature during hot weather when on land. The skin is the main thermoregulatory conduit which emits excessive body heat. Methods: Thorough evaluation of the skin histology in three pinniped species; the California sea lion-Zalophus californianus, the Pacific harbor seal-Phoca vitulina richardsi, and the Northern elephant seal-Mirounga angustirostris, was conducted to identify the presence, location and distribution of skin structures which contribute to thermoregulation. These structures included hair, adipose tissue, sweat glands, vasculature, and arteriovenous anastomoses (AVA). Thermal imaging was performed on live animals of the same species to correlate histological findings with thermal emission of the skin. Results: The presence and distribution of skin structures directly relates to emissivity of the skin in all three species. Emissivity of skin in phocids (Pacific harbor and Northern elephant seals) follows a different pattern than skin in otariids (California sea lions). The flipper skin in phocids tends to be the most emissive region during hot weather and least emissive during cold weather. On the contrary in otariids, skin of the entire body has a tendency to be emissive during both hot and cold weather. Conclusion: Heat dissipation of the skin directly relates to the presence and distribution of skin structures in all three species. Different skin thermal dissipation patterns were observed in phocid versus otariid seals. Observed thermal patterns can be used for proper understanding of optimum thermal needs of seals housed in research facilities, rescue centers and zoo exhibits.     

Presenteeism towards absenteeism: manual work versus sedentary work, private versus governmental--a Croatian review

The research objectives were to find out the extent of presenteeism and absenteeism in manual workers and whether it differs in clerks that perform sedentary jobs. For that purpose 121 manual workers of "3.maj" were polled, of whom 61 are employed by the shipyard in state ownership and 60 are sub-contracted workers. Also 120 clerks were interviewed, 60 postal employees of "Telecom" Zadar and 60 of the police administration. The Stanford Presenteeism Scale (SPS-6), the internationally recognized questionnaire for assessing presenteeism was used as well as the Rijeka Presenteeism Scale (RPS-6), the new questionnaire compiled for this research, and also the Rijeka Absenteeism Scale (RAS-6). The results have shown that in our country the RPS-6 test is adequate for assessment of presenteeism with high reliability for this type of testing, Crombach's alpha = 0.757. The RAS-6 test has shown a low level of reliability and so have our questions on absenteeism which therefore cannot be considered an official scale. All four groups of employees have shown high positive presenteeism with no considerable differences, p = 0.3610, p > 0.05. Only when the question referred to one's performing efficient work with maximum care there were considerable differences p = 0.023, p < 0.05. The research has shown that the use of SPS-6 is not suitable in our parts probably because of cross-cultural differences, reasoning and speech differences. The research has also shown that the notion presenteeism as a positive presenteeism has to be distinguished from the "sickness-presenteeism" for which the SPS-6 scale could conditionally be suitable, which showed medium presenteeism in our workers, but that cannot be considered reliable due to low correlations. To conclude, although the workers show good, positive presenteeism the working conditions are to be further enhanced as well as the contact with the company management, to maintain such presenteeism and not to exhaust the worker's positive energy.     

Expression of Na+-D-glucose cotransporter SGLT2 in rodents is kidney-specific and exhibits sex and species differences

With a novel antibody against the rat Na(+)-D-glucose cotransporter SGLT2 (rSGLT2-Ab), which does not cross-react with rSGLT1 or rSGLT3, the ～75-kDa rSGLT2 protein was localized to the brush-border membrane (BBM) of the renal proximal tubule S1 and S2 segments (S1 > S2) with female-dominant expression in adult rats, whereas rSglt2 mRNA expression was similar in both sexes. Castration of adult males increased the abundance of rSGLT2 protein; this increase was further enhanced by estradiol and prevented by testosterone treatment. In the renal BBM vesicles, the rSGLT1-independent uptake of [(14)C]-α-methyl-D-glucopyranoside was similar in females and males, suggesting functional contribution of another Na(+)-D-glucose cotransporter to glucose reabsorption. Since immunoreactivity of rSGLT2-Ab could not be detected with certainty in rat extrarenal organs, the SGLT2 protein was immunocharacterized with the same antibody in wild-type (WT) mice, with SGLT2-deficient (Sglt2 knockout) mice as negative control. In WT mice, renal localization of mSGLT2 protein was similar to that in rats, whereas in extrarenal organs neither mSGLT2 protein nor mSglt2 mRNA expression was detected. At variance to the findings in rats, the abundance of mSGLT2 protein in the mouse kidneys was male dominant, whereas the expression of mSglt2 mRNA was female dominant. Our results indicate that in rodents the expression of SGLT2 is kidney-specific and point to distinct sex and species differences in SGLT2 protein expression that cannot be explained by differences in mRNA.     

Active-site residue,domain and module swaps in modular polyketide synthases

Sequence comparisons of multiple acyltransferase (AT) domains from modular polyketide synthases (PKSs) have highlighted a correlation between a short sequence motif and the nature of the extender unit selected. When this motif was specifically altered in the bimodular model PKS DEBS1-TE of Saccharopolyspora erythraea, the products included triketide lactones in which acetate extension units had been incorporated instead of propionate units at the predicted positions. We also describe a cassette system for convenient construction of hybrid modular PKSs based on the tylosin PKS in Streptomyces fradiae and demonstrate its use in domain and module swaps.     

Periodontal conditions in individuals with Down's syndrome

Periodontal disease in Down's syndrome (DS) population seems to be a more common and serious problem than caries. The aim of this study was to assess the state of periodontal structures in patients with DS. The Community Periodontal Index of Treatment Needs was used for periodontal status assessment in 71 DS subjects aged 9-34 years. A control group consisted of 71 age- and sex-matched healthy individuals. Both groups were divided into three age groups: 9-15 (n = 24); 16-25 (n = 32); and 26-34 (n = 15) years. The results showed a similar percentage of subjects with bleeding and calculus. The intact periodontium was significantly higher in control than in DS (16.9% vs. none; p < 0.01). Deep pockets were more frequent in DS group than in the control group (14.1% vs. 1.4%; p < 0.01). The mean number of sextants with healthy tissue was lower, and of those with bleeding, calculus and shallow pockets significantly higher in DS patients than in controls (p < 0.01), so all DS subjects required some periodontal treatment (p < 0.01). It can be concluded that the severity of periodontal disease and the treatment needs seem to be significantly greater in DS than in healthy subjects.     

Carotid bifurcation position and branching angle in patients with atherosclerotic carotid disease

Carotid artery bifurcation (CB) is the preferred site for development of atherosclerosis (AS) in extracranial cerebral arteries; internal carotid artery stenosis is the most common cause of ischemic stroke. The frequent atherosclerotic disease of CB may best be explained by the hemodynamic influence of complex blood flow that results from the unique geometry of the bifurcation. Few papers analyze all possible geometric structural characteristics of this bifurcation. While performing many carotid endarterectomies, we noticed that a certain correlation between CB height in the neck and its angle existed, that a larger angle is accompanied with increased frequency of elongation and kinking and that CB shape influences distribution of atherosclerosis. The purpose of this paper is to quantify and evaluate these clinical observations. Radiogrametric analysis of 154 bi-plane orthogonal aortic arch arteriograms of patients with symptomatic atherosclerotic carotid artery disease was performed and a total of 289 CBs were analyzed. The CB height in relation to cervical spine segments was measured and real angles of each bifurcation were calculated. A positive linear correlation between CB height and angle exists: the CB angle increases /decreases 3.34 degrees for each third of the cervical vertebral body height or intervertebral space height. The CB is positioned a little higher on the left side. The proximal border of the atherosclerotic process is found at the level of intersection of the axes of the common carotid artery branches in 92.6% of examined CBs. In lower CBs (with smaller angles) the proximal border was located in the last segment of the common carotid artery, while in high bifurcations (wider angles) the proximal border of the AS process is more distally in the blood flow, in the beginning of the internal carotid artery, and the process was more extensive. High CBs are more suitable for eversion endarterectomy while normal and low CBs are more suitable for open (classic) carotid endarterectomy. The influence of the geometric risk factor demands further investigation.