Does prior PCNL affect RIRS? A retrospective analysis of a single center data.

PURPOSE: The aim of this study is to investigate the results and safety of retrograde intrarenal surgery (RIRS) in patients who have previously undergone percutaneous nephrolithotomy (PCNL). METHODS: A retrospective analysis included patients who underwent RIRS for kidney stones between August 2018 and April 2023. Group 1 comprised 396 patients who underwent primary RIRS, while Group 2 included 231 individuals who had RIRS after previous PCNL. Evaluation parameters included preoperative characteristics, stone attributes, operative details, treatment outcomes, stone-free status, and complications. Statistical analysis utilized Student's t test, Mann-Whitney U test, and Pearson Chi-square test (p < 0.05). RESULTS: The mean age, body mass index, stone number, mean stone burden, and SFS were not statistically different between the groups. Lower pole stones were identified in 144 patients in Group 1 and 88 patients in Group 2 (p = 0.315). In Group 1 and Group 2, the mean operation time and fluoroscopy time were 65.23 ± 18.1 min, 81.32 ± 14.3 min, 26.34 ± 8.31 s, 46.61 ± 7.6 s, respectively, showing statistically significant differences between the groups (p = 0.013, p < 0.001, respectively). Infundibulum stenosis was identified and treated with a laser in 12% of Group 2 cases. Complications occurred in 12 patients in Group 1 and 14 patients in Group 2 (p = 0.136). CONCLUSION: A history of PCNL may contribute to extended operation times and increased fluoroscopy exposure in subsequent RIRS without significantly affecting postoperative SFS or complication rates.

Choline or CDP-choline restores hypotension and improves myocardial and respiratory functions in dogs with experimentally - Induced endotoxic shock.

Endotoxin shock is associated with severe impairments in cardiovascular and respiratory functions. We showed previously that choline or cytidine-5'-diphosphocholine (CDP-choline) provides beneficial effects in experimental endotoxin shock in dogs. The objective of the present study was to determine the effects of choline or CDP-choline on endotoxin-induced cardiovascular and respiratory dysfunctions. Dogs were treated intravenously (i.v.) with saline or endotoxin (LPS, 0.1 mg/kg) 5 min before i.v. infusion of saline, choline (20 mg/kg) or CDP-choline (70 mg/kg). Blood pressure, cardiac rate, myocardial and left ventricular functions, respiratory rate, blood gases, serum electrolytes and cardiac injury markers were determined before and at 0.5-48 h after endotoxin. Plasma tumor necrosis factor alpha (TNF-α), high mobility group box-1 (HMGB1), catecholamine and nitric oxide (NO) levels were measured 2 h and 24 h after the treatments. Endotoxin caused immediate and sustained reductions in blood pressure, cardiac output, pO2 and pH; changes in left ventricular functions, structure and volume parameters; and elevations in heart rate, respiratory rate, pCO2 and serum electrolytes (Na, K, Cl, Ca and P). Endotoxin also resulted in elevations in blood levels of cardiac injury markers, TNF-α, HMGB1, catecholamine and NO. In choline- or CDP-choline-treated dogs, all endotoxin effects were much smaller in magnitude and shorter in duration than observed values in controls. These data show that treatment with choline or CDP-choline improves functions of cardiovascular and respiratory systems in experimental endotoxemia and suggest that they may be useful in treatment of endotoxin shock in clinical setting.

The clinical impact of the COVID-19 pandemic on daily urological practice: first 3-month multicenter results from Istanbul

Background/aim: The aim of this paper was to determine the general tendencies of urology patients and effect of COVID-19 pandemic on daily urological practice at tertiary centers located in the most affected area in Turkey. Materials and methods: We retrospectively analyzed the data of 39,677 patients (group 1) that applied to 6 different large-volume tertiary centers in Istanbul for outpatient consultation, surgery, or other procedures in the 3-month period between March 16 and June 14, 2020. The distribution of the number of patients who applied to subspecialty sections of urology outpatient clinics and inpatient services were recorded by weeks. That data was compared to data obtained from 145,247 patients that applied to the same centers in the same period of the previous year (group 2). The reflection of worldwide and Turkish COVID-19 case distribution on the daily urological practice was analyzed. Results: There was a decrease in the number of patients in all subspecialty sections the in group 1 compared to group 2; however, there was a significant proportional increase in urooncology and general urology admissions. A decrease of approximately 75% was observed in the total number of surgeries (p < 0.001). We detected a negative correlation between the numbers of admission to all outpatient clinics and COVID-19 cases or deaths in Turkey (p < 0.05). The same negative correlation was present for all surgical procedures and consultations (p < 0.05). The multivariate linear regression analysis revealed that the number of cases in Turkey, and the number of deaths worldwide affect the number of outpatient clinic admissions (R2 = 0.38, p = 0.028) and urological surgery (R2 = 0.33, p = 0.020) in Turkey negatively. Conclusion: This novel pandemic has implications even for urology practice. Urological surgical procedures were more affected by COVID-19-related deaths in Turkey and worldwide. Outpatient admissions and urological surgeries decreased significantly by increasing COVID-19 case numbers in Turkey and worldwide deaths.

Prediction of non-muscle-invasive bladder cancer recurrence during intravesical BCG immunotherapy by use of peripheral blood eosinophil count and percentage: a preliminary report.

OBJECTIVES: To determine whether there is an association between blood eosinophil count and percentage with the recurrence of nonmuscle invasive bladder cancer (NMIBC) during Bacillus Calmette-Guérin (BCG) maintenance therapy with our preliminary results. METHODS: A total of 53 patients with NMIBC underwent BCG immunotherapy between January 2015 and September 2018, and met our inclusion criteria were included in the study. The parameters age, gender, smoking status, comorbidity, blood neutrophil, lymphocyte and eosinophil counts, blood eosinophil percentage, previous single postoperative intravesical chemotherapy instillation, tumor characteristic, and total and maintenance dose numbers of BCG were extracted from our medical records and compared between patients with response and with recurrence. RESULTS: Blood eosinophil count and percentage were significantly higher in patients with recurrence compared to patients with response (0.263 ± 0.37 vs. 0.0134 ± 0.021, p = 0.01 and 0.31 ± 0.29 vs. 0.17 ± 0.27, p = 0.01). Other parameters were similar in patients with recurrence and response. Receiver-operating characteristic analysis showed a considerable diagnostic value of blood eosinophil count and percentage in the prediction of bladder cancer recurrence during BCG immunotherapy. CONCLUSION: Blood eosinophil count and percentage in patients with NMIBC can predict the disease recurrence during the BCG immunotherapy. Our research raised new questions and assumptions about the role of eosinophils during BCG immunotherapy.

Radiation Exposure of Surgical Team During Endourological Procedures: International Atomic Energy Agency-South-Eastern European Group for Urolithiasis Research Study.

Introduction: Fluoroscopy-guided endourology procedures require proper radiation protection to minimize radiation risk. This multicenter study aimed at investigating radiation protection practice and related radiation exposure of operating team members. Materials and Methods: Six endourology centers from the South-Eastern European Group for Urolithiasis Research answered questionnaires and collected data of 315 procedures performed within a 3-months period, with simultaneous measurement of dose to staff and dose area product (DAP) to patient. A pair of calibrated personal dosimeters, one for body and one for eye-lens dose, was worn by all key staff members. Dosimeters were centrally calibrated, measured, and analyzed. Results: The annual workload ranged from 173 to 865 procedures per center. Practice of personal dose monitoring and use of radiation protection shielding was found to be inconsistent. Lead aprons and thyroid collars were used by all, whereas protective eyewear was used in only half of centers. Due to the regular use of protective aprons, the whole-body dose of all 44 monitored staff members was safely below the regulatory dose limits. Eye-lens dose of 17 (14 urologists and 3 assisting staff) was above the dosimeter detection level, and dose per procedure varied from <10 to 63 µSv. The highest annual eye-lens dose of 13.5 mSv was found for the surgeon in the busiest department by using an over-the-couch X-ray tube without a ceiling suspended screen. Working closer to patient body with no protection resulted in a six-time higher eye-lens dose per DAP for a surgeon compared with others in the same center. Lower eye-dose per procedure was associated with lower DAP to patient and with the use of an under-the-couch tube, lower fluoroscopy pulse rate, collimation, fluoroscopy time, and acquired images. Conclusions: The study results call for the need to establish standard protocols about use of fluoroscopy during endourology procedures and to increase radiation protection knowledge and awareness of surgical staff.

Radiation exposure of patients during endourological procedures: IAEA-SEGUR study.

Fluoroscopy is increasingly used to guide minimally invasive endourological procedures and optimised protocols are needed to minimise radiation exposure while achieving best treatment results. This multi-center study of radiation exposure of patients was conducted by the South-Eastern European Group for Urolithiasis Research (SEGUR), in cooperation with the International Atomic Energy Agency. Seven clinical centers from the SEGUR group collected data for 325 procedures performed within a three-months period, including standard percutaneous nephrolithotomy (PCNL), mini PCNL, retrograde intrarenal surgery (RIRS), semirigid ureterorenoscopy (URS) and flexible URS. Data included: air kerma area product (PKA), air kerma at the patient entrance reference point (Ka,r), fluoroscopy time (FT), number of radiographic images (N) and fluoroscopy pulse rate, as well as total procedure duration, size and location of stones. Data were centrally analysed and statistically compared. MedianPKAvalues per center varied 2-fold for RIRS (0.80-1.79 Gy cm2), 7.1 fold for mini-PCNL (1.39-9.90 Gy cm2), 7.3 fold for PCNL (2.40-17.50 Gy cm2), 19 fold (0.13-2.51 Gy cm2) for semi-rigid URS and 29-fold for flexible URS (0.10-2.90 Gy cm2). LowerPKAandKa,rwere associated with use of lower FT,Nand lower fluoroscopy pulse rate. FT varied from 0.1 to 14 min, a small fraction of the total procedure time, ranging from 10 to 225 min. HigherNwas associated with higherPKAandKa,r. Higher medianPKAin PCNL was associated with the use of supine compared to prone position. No correlation was found between the concrement size and procedure duration, FT,PKAorKa,r. Dose values for RIRS were significantly lower compared to PCNL. The maximumKa,rvalue of 377 mGy was under the threshold for radiation induced skin erythema. The study demonstrated a potential for patient dose reduction by lowering FT andN, using pulsed fluoroscopy and beam collimation.

The Use of Three Different Hemostatic Agents during Laparoscopic Partial Nephrectomy: A Comparison of Surgical and Early Renal Functional Outcomes.

OBJECTIVE: This study aimed to compare the effects of three different hemostatic agents on surgical and early renal functional outcomes after laparoscopic partial nephrectomy (LPN). MATERIALS AND METHODS: A total of 126 cases of LPN performed between November 2008 and September 2016 were enrolled in this study. Spongostan™ Absorbable Hemostatic Gelatin Sponge (Ethicon, Somerville, NJ, USA) or Surgicel® Original Absorbable Hemostat (Ethicon, Somerville, NJ, USA), or a total of 5 mL of Floseal® Hemostatic Matrix (Baxter Healthcare, Deerfield, IL) was used for additional hemostasis. According to the hemostatic agent used, patients were divided into three groups; and patient characteristics, body mass index (BMI), American Society of Anesthesiologists (ASA) score, tumor characteristics, perioperative parameters, serum creatinine levels, and complications were compared among these three groups. RESULTS: Age, BMI, ASA score, tumor characteristics, operative time, warm ischemia time, complication rates, and length of hospital stay were similar among the groups, whereas estimated blood loss was significantly lower in the Floseal Group (p=0.01). Postoperative serum creatinine levels and differences between preoperative and postoperative serum creatinine levels were also similar among the groups. CONCLUSION: The type of hemostatic agent used in LPN may affect the estimated blood loss. However, it has no substantial effect on other surgical parameters and early renal functional outcomes.

Early Stage Alterations in CA1 Extracellular Region Proteins Indicate Dysregulation of IL6 and Iron Homeostasis in the 5XFAD Alzheimer's Disease Mouse Model.

In recent years, an increasing number of research papers revealed that the compositional and volumetric alterations in the extracellular matrix are the consequences of aging and may be related to Alzheimer's disease (AD). In this study, we aimed to demonstrate the alterations in hippocampal extracellular fluid proteins in vivo using the 5XFAD mouse model. Samples were obtained from hippocampi of 5XFAD mice (n = 6) and their non-transgenic littermates by intracerebral push-pull perfusion technique at 3 months of age, representing the pre-pathological stage of the AD. Proteins in the hippocampal perfusates were analyzed by Ultra Performance Liquid Chromatography-Electrospray Ionization Quadrupole Time-of-Flight Mass Spectrometry (UPLC-ESI-qTOF-MS/MS). 178 proteins were identified and 19 proteins of them were found to be statistically significantly altered (p≤0.05, fold change ≥40%, unique peptide count ≥3) in the hippocampal CA1 extracellular fluid of the 5XFAD mouse model. Ingenuity pathway analysis of the protein expression results identified IL6 as an upstream regulator. The upregulation of IL6 was validated by immunohistochemical staining of the hippocampus and cortex of the 5XFAD mice prior to Aß plaque formation. Furthermore, the iron level in the hippocampus was measured by inductively coupled plasma-mass spectrometry as IL6 is mentioned in several studies to take part in iron homeostasis and inflammation and found to be increased in 5XFAD mice hippocampus. Alterations in extracellular matrix proteins in addition to increasing amount of hippocampal IL6 and iron in the early stages of AD may reveal inflammation-mediated iron dyshomeostasis in the early stages of neurodegeneration.

Comparison of Percutaneous Nephrolithotomy and Retrograde Intrarenal Surgery in Treating 20-40 mm Renal Stones.

PURPOSE: To compare the outcomes of percutaneous nephrolithotomy (PCNL) and retrograde intrarenal surgery (RIRS) in treating renal stones between 20 and 40 mm in diameter. MATERIALS AND METHODS: 146 patients, who were treated with RIRS and 146 patients, who were treated with PCNL for renal stones between 20 and 40 mm in diameter were compared retrospectively using a matched-pair analysis. The operative and post-operative outcomes of both groups were analyzed retrospectively. RESULTS: The mean age, gender, body mass index and stone laterality were similar between the groups. The mean stone size was 28.39 ± 4.67 mm for the PCNL group and 25.08 ± 6.07 mm for the RIRS group (P =.21). The mean operative times were statistically longer in the RIRS group, whereas the fluoroscopy times, hospitalization times and post-operative visual analogue scores were statistically higher in the PCNL group. The stone- free rates (SFR) after a single procedure were 91.7% in the PCNL group and 74% in the RIRS group (P = .04). After auxiliary procedures, the overall SFRs reached 94.4% for the PCNL group and 92.3% for the RIRS group (P = .52). No major complications were observed for both groups. Minor complication (Clavien 1-3) rates were 6.8% and 3.4% for the PCNL and RIRS group, respectively (P =.18). CONCLUSION: RIRS has some advantages over PCNL such as shorter hospitalization times, shorter fluoroscopy times and less post-operative pain in treating renal stones between 20 and 40 mm in diameter. However, PCNL has a higher SFR with only a single session.

Prognostic significance of survivin, ß-catenin and p53 expression in urothelial carcinoma.

Survivin, ß-catenin, and p53 are well-known cell-cycle and apoptosis regulators of tumorigenesis. Urothelial carcinomas (UCs) are the most common of the human cancers. Compared to superficial tumors (Ta, CIS, or T1), invasive UCs are important with regard to recurrence, progression, and mortality. Therefore, we examined whether survivin, ß-catenin, and p53 could be used as the biomarkers for the early prediction of the invasiveness of UCs and the overall survival of the patients. We investigated the prognostic expressions of those biomarkers in UC (n=147) and in non-muscle invasive UC (NMI-UC) (n=113), using tissue microarray and immunohistochemistry. Spearman's correlation analysis and multivariate Cox regression analyses were used for statistical interpretation. High expressions of ß-catenin, survivin, and p53 were associated with a high T stage, recurrence, progression, mortality, low recurrence-free survival, low progression-free survival and low overall survival (p <0.01). Similar findings were achieved for recurrence and progression in the NMI-UC group, except for mortality. Moreover, a positive correlation was shown between p53 and ß-catenin and between p53 and survivin (r=0.221, p <0.01; r=0.236, p <0.01, respectively). Survivin, p53, and ß-catenin overexpression, as prognostic markers, might suggest that the UCs are biologically aggressive with the poor prognosis. Thus, dysregulation of those these cell-cycle and apoptosis regulators in bladder carcinoma could be used as a molecular marker to determine the best treatment strategy and could contribute to the development of targeted therapies.

Comparison of different ureteroscope sizes in treating ureteral calculi in adult patients.

OBJECTIVE: To compare the success and complication rates of a 4.5-6.5F semirigid ureteroscope (S-URS) with an 8.5-11.5F S-URS in treating ureteral stones in adult patients. MATERIALS AND METHODS: Fifty-two patients with ureteral stones, who were treated with 4.5-6.5F S-URS (group 1) and 52 patients who were treated with 8.5-11.5F S-URS (group 2) were compared retrospectively using a matched-pair analysis. The size, lateralization, location, and impaction of the stones and also the patient age, gender, body mass index, and the presence of hydronephrosis were used as the matching parameters. The stones were fragmented with Holmium-YAG laser. RESULTS: The matching parameters were comparable between the 2 groups. The stone-free rates were 88.5% in group 1 and 84.6% in group 2 (P = .566) after a single procedure. The mean operative times for groups 1 and 2 were 32.7 ± 5.8 and 30.2 ± 5.4 minutes, respectively (P = .06). Postoperative hematuria was detected in 1.9% and 13.5% of patients in groups 1 and 2 (P = .027). Ureteral balloon dilation was needed in 1.9% and 15.4% of patients in groups 1 and 2, respectively (P = .015). Mucosal injury was observed in 1.9% and 13.5% of the patients in groups 1 and 2, respectively (P = .027). No major complications were noted in either group. CONCLUSION: Although the stone-free rates and operative times were similar between the 2 groups, a 4.5-6.5F ureteroscope can reduce the need for ureteral balloon dilation and some minor complications, such as mucosal injury and postoperative hematuria, in adult patients.

Prevention of epidural fibrosis in rats by local or systemic administration of citicoline.

AIM: The objective of this study was to investigate the effect of citicoline administration on epidural fibrosis which is a frequent complication of lumbar disc surgery with no effective treatment or preventive surgical technique. MATERIAL AND METHODS: Sixty Sprague-Dawley female rats undergoing L4-5 right hemilaminotomy and annular fenestration were arranged in three groups: rats in Group 1 (control group) and Group 2 (topical citicoline group) were applied 0,9% saline and 100 µM citicoline on surgical area, respectively, while rats in Group 3 (systemic citicoline group) received 600 µmol/kg citicoline intraperitoneally. Rats were sacrificed four weeks later and their vertebral colons were removed en bloc. Groups were evaluated according to histological criteria and results were compared using statistical tools. RESULTS: Compared with control group, significantly less epidural fibrosis, dural adhesion, fibroblast cell density, foreign body reaction, and medulla spinalis retraction were observed in groups treated with topical and systemic citicoline (groups 2 and 3) (p < 0,001). No significant difference was found with regard to measured parameters between two treatment groups (p > 0,05). CONCLUSION: Our study demonstrates for the first time in the literature that citicoline may be effective for preventing postoperative epidural fibrosis. However, its mechanism of action and clinical effectiveness must be further investigated.

CDP-choline and its endogenous metabolites, cytidine and choline, promote the nerve regeneration and improve the functional recovery of injured rat sciatic nerves.

OBJECTIVE: Topical cytidine-5'-diphosphocholine (CDP-choline) has been shown to improve the functional recovery and promote the nerve regeneration of injured sciatic nerves in rats. The aims of this study were to test whether CDP-choline was effective at promoting nerve healing when the surgery to repair an injury was delayed and to determine whether the cytidine and/or the choline moieties of CDP-choline contribute to its beneficial actions. METHODS: One hundred and fifty Sprague-Dawley rats underwent a surgical procedure that involved damaging the right sciatic nerve and suturing the epineurium. The injured sciatic nerve was either repaired immediately (on the first day) or on the third day after surgery. Rats were assigned to one of five groups and received a topical application of either 0.4 ml of saline (control) or 0.4 ml of 100 µM CDP-choline, cytidine, choline, or cytidine+choline. RESULTS: The sciatic function index (SFI) of the rats in both groups (those who had their nerve repair immediately versus those on day 3) improved gradually by 4, 8, and 12 weeks after surgery. The percentage recovery in SFI score was significantly higher in rats treated with CDP-choline or cytidine+choline at all time points. Axon count increased by ∼50% in rats treated either with CDP-choline or cytidine+choline. Treatment with CDP-choline or cytidine+choline reduced scar formation and decreased nerve adherence when the sciatic nerve was repaired immediately, and rats treated with CDP-choline or cytidine+choline had better axonal organization than control rats. Treatment with choline or cytidine alone led to a less marked improvement in SFI score and failed to increase axon count. CONCLUSION: Our results demonstrate that CDP-choline, as well as the combination of its metabolites, cytidine+choline, improves the functional recovery and promotes the regeneration of injured sciatic nerves treated with immediate or delayed surgical repair in rats.

Elevation of serum cerebral injury markers correlates with serum choline decline after coronary artery bypass grafting surgery.

The aims of this study were to determine circulating choline status and its relationship to circulating levels of S-100beta protein and neuron-specific enolase, biochemical markers of cerebral injury and cognitive decline, after coronary artery bypass grafting (CABG) surgery. Preoperatively, patients scheduled for off-pump or on-pump CABG surgery had serum concentrations of 12.0+/-0.2 and 11.7+/-0.4 micromol/L free choline and 2640+/-65 and 2675+/-115 micromol/L phospholipid-bound choline, respectively. Serum free and bound choline levels decreased by 22-37% or 34-47% and 16-36% or 31-38% at 48 h after off-pump or on-pump surgery, respectively. Serum S-100beta and neuron-specific enolase increased from preoperative values of 0.083+/-0.009 and 6.3+/-0.2 microg/L to 0.405+/-0.022 and 11.4+/-0.8 microg/L, respectively, at 0 h postoperatively and remained elevated for 48 h after off-pump surgery. Serum free and bound choline concentrations were inversely correlated with the concentrations of S-100beta (r=-0.798; p<0.001 and r=-0.734; p<0.001) and neuron-specific enolase (r=-0.840; p<0.001 and r=-0.728; p<0.001). In conclusion, CABG surgery induces a decline in serum free and phospholipid-bound choline concentrations. The decreased serum choline concentrations were inversely correlated with the elevated levels of circulating cerebral injury markers. Thus, a decline in circulating choline may be involved in postoperative cognitive decline.

Endotoxin alters serum-free choline and phospholipid-bound choline concentrations, and choline administration attenuates endotoxin-induced organ injury in dogs.

This study in dogs was performed to assess circulating choline status during endotoxemia and to determine whether choline administration can protect dogs from endotoxin-induced tissue injuries. Baseline serum-free and phospholipid-bound choline concentrations were 19.2 +/- 0.6 micromol/L and 3700 +/- 70 micromol/L, respectively. After intravenous endotoxin infusion, serum-free choline concentrations decreased by 14% to 49% (P < 0.05-0.001) at 2 to 6 h after 0.02 mg/kg endotoxin, and increased by 23% to 98% (P < 0.05-0.001) at 1 to 48 h after 1 mg/kg endotoxin. Serum phospholipid-bound choline concentrations increased by 19% to 27% (P < 0.05) at 12 to 24 h or by 18% to 53% (P < 0.05-0.001) at 1 to 48 h after 0.02 or 1 mg/kg endotoxin, respectively. The changes in serum-free and -bound choline levels in response to endotoxin were accompanied by dose- and time-related elevations in serum cortisol and biochemical markers for tissue injury and/or organ dysfunction. Intravenous administration of choline (20 mg/kg) 5 min before, and 4 and 8 h after endotoxin (1 mg/kg) attenuated endotoxin-induced elevations in serum alanine aminotransferase (P < 0.05-0.001), aspartate aminotransferase (P < 0.05-0.001), gamma-glutamyl transferase (P < 0.05-0.001), alkaline phosphatase (P < 0.05-0.001), lactate dehydrogenase (P < 0.05-0.001), myocardial creatine kinase (P < 0.001), urea (P < 0.05-0.01), creatinine (P < 0.05), uric acid (P < 0.01-0.001), and tissue necrosis factor-alpha (P < 0.001). Choline also attenuated alanine aminotransferase (P < 0.05-0.01), alkaline phosphatase (P < 0.05-0.01), lactate dehydrogenase (P < 0.05-0.01), creatine kinase (P < 0.05-0.001), myocardial creatine kinase (P < 0.05-0.001), and uric acid (P < 0.05-0.01), but failed to alter the serum urea, creatinine, aspartate aminotransferase, and gamma-glutamyl transferase responses to 0.02 mg/kg endotoxin. These data show that choline status is altered during endotoxemia and that choline administration diminishes endotoxin-induced tissue injury.

Investigation of diagnostic importance of platelet closure times measured by Platelet Function Analyzer--PFA 100 in dogs with endotoxemia.

This study was performed to evaluate the diagnostic importance of the platelet closure times measured by the Platelet Function Analyzer (PFA-100) in dogs with endotoxemia. E. coli endotoxin was given intravenously once, at the dose of 0.02 mg/kg or 1 mg/kg in groups I (n=9) and II (n=8), respectively. Normal saline (0.1 ml/kg) was injected in group III (n=8). The dogs were monitored for 48 h, and venous blood samples were collected prior to (baseline) and at intervals of 0.5, 1, 2, 4, 6, 8, 12, 24 and 48 h subsequent to the treatments. The white blood cell (WBC), platelet counts, and hematocrit (Hct) values were recorded. Platelet closure times were determined, using collagen/epinephrine (CEPI) and collagen/adenosine diphosphate (CADP) cartridges. Within 0.5 h after the endotoxin application baseline WBC and platelet counts (mean +/-SD) decreased significantly (p<0.001) to 2000 +/- 500 and 1850 +/- 200 cells/microl or 69.000 +/- 12.500 and 27.000 +/- 6.400 cells/microl in groups I and II, respectively. Platelet counts remained low during the first 1-48 h, but the WBC count was high at the 8th-48th h, in groups I and II, compared with baselines (p<0.001). After the application of the endotoxin, Hct values increased from baseline values of 37 +/- 3 or 39 +/- 2% to 48 +/- 2 or 51 +/- 3%, within 1 h (p<0.001), in groups I and II, respectively. Hct values in group II were notably higher (p<0.001) than those of group I, during the 2nd-48th h. Hematological parameters and closure times did not differ significantly throughout the study in group III. Baseline closure time ranged from 79 +/- 5 seconds (s) to 86 +/- 5 s for CADP and 144 +/- 13 s to 159 +/- 14 s for CEPI in all dogs (n=25). At 0.5 h after the endotoxin, the closure times of CADP as well as CEPI declined to 62 +/- 6 s and 76 +/- 8 s in group I (p<0.001) and 57 +/- 5 s and 75 +/- 6 s in group II (p<0.001). Afterwards, closure time prolonged to the levels of 280 +/- 8 s (CADP) and 294 +/- 5 s (CEPI) by 48 h (p<0.001) in group II, but returned to the baseline limit in group I. In conclusion, our results show that the shortened closure times may serve as a very early diagnostic sign of endotoxemia, prolonged closure times however may be used as an index for the severity of endotoxemia.

Vitamin a deficiency in patients with common variable immunodeficiency.

Vitamin A, a naturally occuring antioxidant micronutrient, has immunomodulating effect in patients with immunodeficiency, including an influence on cytokine production and lymphocyte growth and functions. Vitamin A deficiency is associated with a shift from type 2 cytokines to predominantly type 1 cytokines. The aims of this study were to determine Vitamin A status in Common variable immunodeficiency (CVID) patients and the relationship between Vitamin A status and cytokines production. Serum Vitamin A, neopterin, TNF-alpha, IL-2, IL-4, and IL-10 levels were determined in 19 CVID patients and 15 healthy children. Effects of 9-cis retinal, Vitamin A derivative, on cytokines (TNF-alpha, IL-2, IL-4 and IL-10) production in lymphocytes were tested in vitro condition using lymphocyte cultures obtained from CVID patients and healthy children.Serum Vitamin A level in CVDI patients was, 21.1+/- 1.5 microg/dL, significantly (p < 0.001) lower than the value, 35.7+/- 1.8 microg/dL, observed in healthy children. Serum neopterin level in the patients was, 9.8+/- 2.9 nmol/L, higher (p < 0.05) than the value, 3.9+/- 0.7 nmol/L, observed in control group. Common variable immunodeficiency patients, serum IL-4 level was significantly (p < 0.05) lower than the value observed for healthy children. Serum TNF-alpha, IL-2 and IL-10 levels were similar in the patients and healthy children. Vitamin A derivative, 9-cis retinal, increased TNF-alpha and IL-4 production in cultured mononuclear cells obtained from control and CVID patients. Vitamin A derivative, also, increased IL-2 and Il-4 production in cultured mononuclear cells obtained from CVID patients. These results show that CVID patients have low serum Vitamin A levels and high serum neopterin levels. A supplementation with Vitamin A may have role in downregulation of inflammatory responses in CVID patients.

Declines in serum free and bound choline concentrations in humans after three different types of major surgery.

We examined the changes in circulating choline status in humans in response to major surgery by measuring serum free and phospholipid-bound choline concentrations before, during and 1-72 h after total abdominal hysterectomy, off-pump coronary artery graft surgery or brain tumor surgery. Preoperatively, the mean serum free and phospholipid-bound choline concentrations in patients scheduled for abdominal hysterectomy (n = 26), off-pump coronary artery grafting surgery (n = 34) or brain tumor surgery (n = 24) were 12.3 +/- 0.5, 12.1 +/- 0.4 and 11.4 +/- 0.4 micromol/l, and 2495 +/- 75, 2590 +/- 115 and 2625 +/- 80 micromol/l, respectively. Serum free choline and phospholipid-bound choline concentrations decreased from these baseline values to 8.8 +/- 0.7 (p < 0.001), 8.8 +/- 0.5 (p < 0.001) and 8.2 +/- 0.4 micromol/l (p < 0.001), and 2050 +/- 108 (p < 0.001), 2166 +/- 59 (p < 0.001) and 1884 +/- 104 micromol/l (p < 0.001) at 1 h after hysterectomy, off-pump bypass graft surgery or brain tumor surgery, respectively. They remained at these low levels for 24 h and then gradually increased towards the preoperative values at 48-72 h postoperatively. Serum cortisol increased postoperatively in all surgical patients for 24 h and its levels were inversely correlated with serum free and bound choline concentrations. These results show that circulating free and bound choline concentrations decrease for 72 h after total abdominal hysterectomy, off-pump coronary artery graft surgery or brain tumor surgery in humans.

Serum free and phospholipid-bound choline decrease after surgery and methylprednisolone administration in dogs.

We designed this study to determine whether serum free and phospholipid-bound choline concentrations change after surgery or methylprednisolone treatment in dogs and rats. In dogs, serum free and phospholipid-bound choline concentrations were decreased by 29% and 17% immediately after abdominal-pelvic surgery under xylasine+ketamine anesthesia, respectively, and both remained low for 24 h. Serum cortisol was elevated after surgery. The elevation in serum cortisol was inversely correlated with the decreases in free (r=-0.737; P<0.001) and phospholipid-bound (r=-0.771; P<0.001) choline concentrations. After methyprednisolone administration (5-20 mg/kg) free and phospholipid-bound choline concentrations decreased in a dose- and time-dependent manner. In rats, either surgery or methylprednisolone failed to alter serum free choline concentrations while phospholipid-bound choline decreased after surgery. These data show that the decrease in serum choline after surgery results from the increase in circulating glucocorticoids.