Motor coordination assessment in practicing surgeons and medical students.

INTRODUCTION: Manual and motor coordination skills are commonly believed to be necessary for the surgical profession. AIM OF STUDY: To assess motor coordination skills in medical students, surgical residents and attending surgeons. MATERIAL AND METHODS: The study group consisted of 17 surgeons and 44 medical students. All participants were tested with a number of tests for motor coordination. Statistical analysis with ANOVA/MANOVA methods, contrast analysis and post-hoc test as appropriate. RESULTS: There were no gender related differences in coordination skills. The group of students had significantly lower results in comparison to surgeons. Statistical significance (p < 0.05) was observed in perception diversity test, and Perception-Diversity-Orientation Index. There was no statistically significant difference between residents and attending surgeons CONCLUSION: Our results demonstrated that coordination skills are not related to gender. They may serve as one of the selection criteria to surgical profession. The level of coordination skills is helpful in designing of individual training program.

Brain inflammation, cholesterol, and glutamate as interconnected participants in the pathology of Alzheimer's disease.

Alzheimer's disease (AD) represents one of the most common ailments afflicting the rapidly growing elderly segment of today's population. Despite the vast amount of effort expended in developing a cure, currently approved drugs address only cognitive symptoms that, although important for improving a patient's daily living standard, do not provide a significant delay or halt to disease progression. Early reports that individuals taking anti-inflammatory medications reduce their risk of developing AD has led to the "inflammation hypothesis" of AD and the subsequent testing of these drugs in the clinic. Tests of a select few of these medications in AD clinical trials have, however, yielded disappointing results. Reports of statin-based medications reducing the risk of AD have also led to the testing of this class of drugs in the clinic. Recently, the approval of the NMDA receptor antagonist memantine (Namenda) has provided clinical support for glutamatergic processes in the disease and generated a renewed interest in the role of excitatory amino acids in the etiology of AD. In this review, we take a closer look at these three compelling areas for addressing AD therapeutics: inflammation, cholesterol, and glutamate. We present arguments that these components are interconnected and mutually regulate processes involved in AD progression. Special focus is given to inflammation as a central feature of AD that may be acting in synergy with cholesterol and glutamate to mediate the observed pathophysiology.

The clinical value of parenteral immunonutrition in surgical patients.

BACKGROUND & AIM: To analyze the clinical impact and cost-effectiveness of parenteral immunonutrition (PN). METHODS: Prospective clinical trial of a group of 105 patients operated on for gastric carcinoma between 2001-2003. During the postoperative period, patients were randomly allocated to one of three groups: standard PN (A), PN + glutamine (B) and PN + omega-3-FA (C). The rate and type of complications, hepatic and renal function, cost and treatment tolerance in all groups were analyzed. RESULTS: Postoperative complications were observed in 11 patients (36.6%) in group A, in 7 (23.3%) in B and in 8 (26.6%) in C. The most common complication was pneumonia. Prealbumin concentration and TLC increased faster in groups B and C. The length of hospital stay was significantly shorter in the immunonutrition groups. The cost of PN was highest in C group, while cost of hospital stay was longer in A. CONCLUSIONS: Immunostimulating parenteral nutrition helps to reduce the number of infectious complications, improves the function of the immune system, and has no influence on surgical complications, hepatic and renal function and protein synthesis. The cost of immunostimulating treatment based on omega-3-unsaturated fatty acids is higher than standard.

Pentoxifylline does not affect nociception if administered postoperatively.

Proinflammatory cytokines, such as tumor necrosis factor alpha (TNF-alpha), interleukin-1 (IL-1) and interleukin-6 (IL-6), act as mediators of post-injury inflammation and increase pain sensitivity. Pentoxifylline (PTX) has the property of inhibiting TNF-alpha, IL-1, and IL-6 production. Previous studies revealed that the pre-injury or preoperative administration of PTX inhibited consequent hyperalgesia or postoperative pain. The aim of the study was to determine, if postoperative PTX administration affects postoperative pain. A group of 40 patients undergoing laparotomic cholecystectomy received postoperatively PTX at 10 mg/kg or placebo directly after the termination of general anesthesia. There were no differences in postoperative pain, analgesic drug requirement or TNF-alpha and IL-6 serum levels between the groups.

Amyloid-beta peptide fragments p3 and p4 induce pro-inflammatory cytokine and chemokine production in vitro and in vivo.

Alzheimer's disease (AD) pathology is characterized by senile plaques containing amyloid-beta (A beta) peptide, a protein with neurotoxic and glial immune activating potential. In addition to the highly amyloidogenic peptides A beta(1--40/42), plaques contain amino-terminal truncated A beta peptides including the alpha secretase-generated p3 fragments A beta(17--40/42). In the present study, A beta(17--40/42), A beta(1--40/42), A beta(1--16), and A beta(25--35) aged in different solvents exhibited varying capacity to activate the murine microglia cell line MG-7 depending on solvent, peptide 'aging', and peptide sequence that did not strictly correlate with beta-sheet formation. A beta(17--40/42) or A beta(1--42) stimulated production of the pro-inflammatory cytokines interleukin (IL)-1 alpha, IL-1 beta, IL-6 and tumor necrosis factor-alpha (TNF-alpha), and the chemokine MCP-1 from differentiated human monocytes (THP-1) while little or no stimulation was observed with the other A beta fragments. MG7 cells also produced these five pro-inflammatory proteins in response to A beta(1-42) whereas A beta(17--40/42) elicited mainly TNF-alpha and MCP-1. Murine and human astrocyte cell lines (D30 and U373, respectively) were generally less responsive to A beta fragments producing mainly IL-6 and MCP-1 in response to A beta(1--42) or A beta(17--40/42) fragments. In mice, an intracerebroventricular infusion of A beta(1--42) significantly increased IL-1 alpha, IL-1 beta, IL-6 and MCP-1 while A beta(17--40/42) increased MCP-1 and A beta(17--40) increased IL-1 beta. These results demonstrate that p3 and p4 A beta fragments are pro-inflammatory glial modulators and thus may play a role in development of the immunopathology observed in AD.

IL-4, IL-10 and IL-13 modulate A beta(1--42)-induced cytokine and chemokine production in primary murine microglia and a human monocyte cell line.

A hallmark of the immunopathology associated with Alzheimer's disease (AD) is the presence of activated microglia surrounding senile plaque deposits of beta-amyloid (A beta) peptides. A beta peptides have been shown to be potent activators of microglia and macrophages, but little is known about endogenous factors that may modulate their responses to amyloid. We investigated whether the 'anti-inflammatory' cytokines IL-4, IL-10 and IL-13 could regulate A beta-induced production of the inflammatory cytokines IL-1 alpha, IL-1 beta, TNF-alpha, IL-6 and the chemokine MCP-1. A beta(1-42) time- and dose-dependently induced the production and secretion of these inflammatory proteins in the human THP-1 monocyte cell line and in primary murine microglia, similar to what was observed for lipopolysaccharide (LPS) stimulated cells. IL-10 was found to suppress all A beta and LPS-induced inflammatory proteins measured (IL-1 alpha, IL-1 beta, IL-6, TNF-alpha and MCP-1) in both cell types with the exception of LPS-induced MCP-1 in THP-1 cells where no change was observed. In contrast to the inhibition observed for IL-10, both IL-4 and IL-13 enhanced MCP-1 secretion. IL-4 and IL-13 reduced IL-6 secretion, but effects on IL-1 alpha, IL-1 beta or TNF-alpha were dependent on cell type and stimulus conditions. Additional experiments using RT-PCR showed that IL-4, IL-10 and IL-13 mRNA is found to be present in human brain tissue. These results show that IL-4, IL-10, and IL-13 differentially regulate microglial responses to A beta and may play a role in the inflammation pathology observed surrounding senile plaques.

[Nutritional therapy and the immune system]. / Leczenie zywieniowe a uklad odpornosciowy.

Malnutrition is one of the consequences of chronic and neoplastic diseases. Therefore the attention has been paid recently to the most appropriate nutritional therapy in order to reduce the number of postoperative complications, mortality rates and the length of hospitalisation. Administered nutritional substances should cover basic and calorific demands. However it was observed that malnutrition leads to the state of immunosuppression. Several studies were carried out using potentially immunostimulating substances e.g. nucleotides, some of amino acids, vitamins and trace elements or unsaturated fatty acids, in addition to the nutritional support. The authors are presenting a review of the current state of knowledge and data from clinical trials on the immunostimulating role of the nutritional components.

The effect of pentoxifiline on post-injury hyperalgesia in rats and postoperative pain in patients.

Recent studies demonstrate that activation of proinflammatory cytokines following injury intensifies the process of nociception. The present investigation assessed the influence of pre-injury pentoxifiline (PTFL, a non-specific cytokine inhibitor) on the development of post-injury nociception in animals and patients. It was established that intrathecal or intraperitoneal PTFL, elevated the nociceptive threshold for mechanical stimuli in the formalin test in rats. Pre-injury PTFL also inhibited pain-related behaviour. These findings correlate with a lower TNFalpha level in the serum of animals receiving pre-injury PTFL. In clinical investigations PTFL was administered intravenously before elective cholecystectomy. Patients who received preoperative PTFL had lower opioid requirements in the early postoperative period than control. At the same time, serum levels of TNFalpha and IL6 were lower in the PTFL group. Our results confirm the hypothesis as to the possibility of modulating of nociception through preemptive administration of a cytokine inhibitor.

Enhancement of beta-amyloid precursor protein transcription and expression by the soluble interleukin-6 receptor/interleukin-6 complex.

We investigated a potential role for the soluble interleukin-6 receptor (sIL-6R) in modulating interleukin-6 (IL-6) function in the central nervous system by assessing IL-6 and sIL-6R effects on beta-amyloid precursor protein (beta-APP) transcription and expression in cells of human neuronal origin. Cells transfected with a luciferase reporter plasmid containing a 3.8 kb DNA fragment of the beta-APP promoter were shown to have inducible promoter activity when treated with phorbol ester or basic fibroblast growth factor, but not when treated with lipopolysaccharide or Il-6. PCR amplification analysis revealed the presence of mRNA encoding the signaling subunit of the Il-6 receptor complex, the gp130 subunit, at levels approximating that found in human cortical tissue. The mRNA encoding the IL-6 receptor, however, was poorly expressed and was detectable only at high amplification cycles. When purified sIL-6R protein was added together with IL-6, there was a rapid induction of promoter activity within 2 h of stimulation followed by elevations in protein levels of both cell-associated and secreted beta-APP. Analysis of mRNA transcripts from human cortical brain tissue and cell cultures derived from fetal human brain demonstrated the presence of an alternatively spliced secreted form of the IL-6 receptor mRNA, suggesting that cells of the central nervous system may themselves be a source of sIL-6R protein. The capacity for sIL-6R to enhance IL-6 function and broaden the IL-6 target cell population in the brain has implications for the regulation of beta-APP expression in disease states such as Alzheimer's disease where elevations in brain IL-6 levels have been reported.

[Glutamine--its metabolic role and possibilities for clinical use]. / Glutamina--rola w ustroju i mozliwosci zastosowania klinicznego.

Glutamine has been the point of interest of many nutritional studies concerning parenteral and enteral nutrition. Advantages from glutamine support have been observed previously in animal models. It was shown that glutamine is the energy source for rapidly dividing cells e.g. immune cells, gut mucosa. Recent molecular and protein chemistry studies have begun to define metabolic mechanism of glutamine action, and clinical trials suggest its safe and positive influence on catabolic patients. Parenteral and enteral nutrition enriched with glutamine improves gut integrity and function, decreases infection rate and improves function of immune cells. However, the indications for glutamine enriched nutrition and appropriate protocol of administration need determination. Taken together the data suggest that this amino-acid is an important dietary nutrient and is probably conditionally essential in certain catabolic conditions.

Effects of ritanserin on haloperidol-induced dopamine (D2) receptor up-regulation in the rat.

Rats were treated with vehicle, ritanserin (5 mg/kg, i.p.), haloperidol (1 mg/kg, i.p.) or both ritanserin and haloperidol for 19 days to determine whether chronic administration of the serotonin (5HT2) antagonist ritanserin affects D2 receptor up-regulation produced by haloperidol. Brain sections were prepared for D2 and 5HT2 receptor autoradiography with [3H]spiperone and [3H]ketanserin, respectively. Ritanserin significantly reduced 5HT2 receptors to 80% of vehicle in the sulcal area of the frontal cortex but had no effect on D2 receptors. Haloperidol significantly increased striatal and n. accumbens D2 receptors with no effect on 5HT2 receptors. In ritanserin/haloperidol-treated rats, D2 receptors were significantly increased along with significant decreases in 5HT2 receptors of the frontal cortex. These results suggest 5HT2 receptor antagonism by ritanserin does not significantly affect D2 receptor up-regulation produced by haloperidol.

Ex vivo studies with iloperidone (HP 873), a potential atypical antipsychotic with dopamine D2/5-hydroxytryptamine2 receptor antagonist activity.

Iloperidone {HP 873: 1-[4-[3-[4-(6-fluoro-1, 2-benzisoxazol-3-yl)-1-piperidinyl]propoxy] -3-methoxyphenyl]ethanone} is a dopamine (D2)/serotonin (5-HT2) receptor antagonist with the preclinical profile of an atypical antipsychotic based on biochemical studies in rats. Iloperidone significantly increased dopa accumulation, an index of dopamine turnover in response to D2 receptor blockade, at doses from 0.3 to 10 mg/kg i.p. in the striatum and from 1 to 10 mg/kg in the nucleus accumbens. Blockade of dopaminergic presynaptic autoreceptors was measured by the reversal of apomorphine-inhibition of gamma-butyrolactone-induced dopa synthesis. Iloperidone did not significantly reverse the apomorphine inhibition of gamma-butyrolactone-induced dopa synthesis at any of the doses tested (0.3-10 mg/kg i.p.). In ex vivo receptor autoradiography studies, a 30-min pretreatment with iloperidone (2.5-20 mg/kg i.p.) inhibited the binding of [3H]spiperone to cortical and subcortical 5-HT2 receptors by 42 to 94%, in contrast to only 1 to 15% inhibition of [3H]spiperone binding to D2 receptors in the nucleus accumbens and striatum. Iloperidone, at 2.5 mg/kg i.p., inhibited 5-HT2 receptor binding by 54 to 62% at 4-hr post-treatment, whereas there was negligible inhibition of D2 receptors. Chronic treatment with 5 mg/kg i.p. of iloperidone for 19 days significantly decreased the number of 5-HT2 receptors in the frontal cortex with no change in receptor affinity. D2 receptor number and affinity were unchanged in the nucleus accumbens and six regions of the striatum. In summary, iloperidone is a 5-HT and dopamine receptor antagonist with weak activity at presynaptic dopamine autoreceptors. Potent 5-HT2 receptor antagonism may be an important component in the preclinical profile of iloperidone as a potential atypical antipsychotic.

Tyrosine phosphorylation of inducible nitric oxide synthase: implications for potential post-translational regulation.

The activation of cultured Raw 264.7 murine macrophages with interferon gamma and lipopolysaccharide results in the expression of inducible nitric oxide synthase (i_NOS) and the subsequent production of nitric oxide. In the present study, the i-NOS expressed in these activated cells was characterized for possible post-translational protein modification by endogenous tyrosine protein kinases. Western-blot analysis using phosphotyrosine antibodies revealed that i-NOS was phosphorylated on tyrosine residues and that this was an early event coinciding with the appearance of newly synthesized i-NOS. A brief exposure of activated cells to vanadate, a tyrosine phosphatase inhibitor, significantly increased the level of i-NOS tyrosine phosphorylation, suggesting that tyrosine phosphatases are dynamically involved in the regulation of this process. Vanadate treatment of activated cells also resulted in a rapid increase in enzyme activity, occurring within 5 min of exposure. Taken together, these results demonstrate that tyrosine kinases and phosphatases are involved in the post-translational modification of i-NOS and may potentially play a role in modulating the functional activity of the enzyme in macrophages.

Effects of chronic intrahippocampal infusion of lipopolysaccharide in the rat.

Astrogliosis and microglial activation are associated with many neurodegenerative disorders including multiple sclerosis, its animal model experimental allergic encephalomyelitis, and Alzheimer's disease. To address the hypothesis that chronic astroglial or microglial activation could be contributing factors to neuronal death or injury, the immunostimulant lipopolysaccharide was infused into the hippocampus for 16 days using Alzet mini-osmotic pumps attached to a cannula. Placement of the cannula and infusion of vehicle for 16 days caused a hippocampal lesion with a volume of 0.5 +/- 0.1 mm3. Infusion of lipopolysaccharide at the dose of 2.0 micrograms/day produced a lesion of 4.9 +/- 1.3 mm3 (P < 0.01, Newman-Keuls), whereas, a lower dose of 0.2 microgram/day caused a lesion of 1.3 +/- 0.3 mm3 (P < 0.05). The lesion was defined as a focal necrotic reaction with fibrin deposits outlining an area at an early stage of encapsulation. No apparent neuronal loss was observed by Cresyl Violet staining outside the encapsulated necrotic area. There was a pronounced astrogliosis and an increase in activated macrophages throughout the lipopolysaccharide-infused hippocampus as determined by glial fibrillary acidic protein and ED-1 immunohistochemistry, respectively. Choline acetyltransferase and glutamic acid decarboxylase enzyme activities, used as functional measures of neuronal viability for cholinergic and GABAergic neurons, respectively, were unaffected in the hippocampus following a 16 day infusion of lipopolysaccharide at the doses of 0.2, 0.6 and 2.0 micrograms/day. In addition, unilateral infusion of lipopolysaccharide into the hippocampus did not affect 24 h locomotion when tested on day 13, body temperature or weight gain. Under the experimental conditions employed in the present study, chronic infusion of lipopolysaccharide into the hippocampus resulted in a dose-dependent focal necrotic lesion at the site of infusion. In tissue surrounding the encapsulated lesion, neurons were present among the reactive astrocytes and increased number of macrophages suggesting that astrocytes and macrophages can be activated without causing neuronal loss.

Quantitative analysis of specific mRNA transcripts using a competitive PCR assay with electrochemiluminescent detection.

Reverse transcriptase-polymerase chain reaction (RT--PCR) has been widely utilized for both the qualitative and quantitative assessment of the levels of specific mRNA transcripts in living systems. Quantitation of specific transcripts has often proved to be problematic because of the difficulty associated with relating the PCR-amplified product to the starting cDNA representing the mRNA of interest. We have overcome these difficulties and have developed a competitive PCR assay employing the property of electrochemiluminescence for the detection of PCR products. This assay possesses the dual advantage of being both nonradioactive and highly sensitive.

[Respiratory infections in the surgical intensive care unit]. / Zakazenia ukladu oddechowego w oddziale chirurgicznej intensywnej terapii.

The purpose of the study was to assess microbiological structure and the influence of the predisposing factors on frequency of lower respiratory tract infections. The study group consisted of 72 patients admitted to the Intensive Care Unit between January and October 1994. We found that 27 pts. (39%) developed respiratory infections. The risk of an infection was much higher in the group with long (over 5 days) stay on ICU, which required artificial ventilation as well as in the group of patients treated due to acute pancreatitis. More than 75% of isolated strains were Gram negative bacteria. Using susceptibility tests we conclude that Pseudomonas aeruginosa, Serratia, and Acinetobacter baumanii are highly resistant to antibiotics. The results suggests that 3rd generation cephalosporins and imipenem are most efficient in vitro.

Effects of acute and chronic treatments with clozapine and haloperidol on serotonin (5-HT2) and dopamine (D2) receptors in the rat brain.

The effects of acute and chronic treatments with haloperidol or clozapine on the binding of [3H]spiperone to D2 and 5-HT2 receptors were examined in 6 discrete regions of the striatum, n. accumbens and frontal cortex using quantitative autoradiography. Acute treatment with haloperidol, 0.1-2.0 mg/kg, i.p., produced a dose-dependent reduction to 60% of control in the binding of [3H]spiperone to D2 receptors in the striatum and n. accumbens and no effect on the binding of [3H]spiperone to 5-HT2 receptors in the striatum, n. accumbens or frontal cortex. Acute treatment with clozapine, 10-40 mg/kg, i.p., produced a dose-dependent reduction in D2-specific binding in both the n. accumbens and the striatum and also significant reductions to 24% of control in the binding of [3H]spiperone to cortical 5-HT2 receptors. Chronic treatment with haloperidol, 1 mg/kg/day, i.p., significantly increased (40-65%) the maximal number of D2-specific [3H]spiperone binding sites in the n. accumbens and the dorsolateral and ventrolateral regions of the striatum, whereas small increases (20-29%) were seen in the ventromedial, dorsomedial, rostral and caudal regions of the striatum. Chronic treatment with clozapine, 20 mg/kg/day, i.p., did not change the maximal number of D2 receptors in the n. accumbens or any region of the striatum. Chronic treatments with clozapine produced a decrease in the maximal number of cortical 5-HT2 receptors to 55% of control whereas haloperidol had no effect. This study demonstrates regional differences in the up-regulation of striatal D2 receptors following chronic treatment with haloperidol and different effects of a typical and atypical neuroleptic on 5-HT2 receptors following acute and chronic treatments.