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Antibiotic resistance of E. coli in sewage and sludge.

The aim of the study is the evaluation of resistance patterns of E. coli in wastewater treatment plants without an evaluation of basic antibiotic resistance mechanisms. Investigations have been done in sewage, sludge and receiving waters from three different sewage treatment plants in southern Austria. A total of 767 E. coli isolates were tested regarding their resistance to 24 different antibiotics. The highest resistance rates were found in E. coli strains of a sewage treatment plant which treats not only municipal sewage but also sewage from a hospital. Among the antimicrobial agents tested, the highest resistance rates in the penicillin group were found for Ampicillin (AM) (up to 18%) and Piperacillin (PIP) (up to 12%); in the cephalosporin group for Cefalothin (CF) (up to 35%) and Cefuroxime-Axetil (CXMAX) (up to 11%); in the group of quinolones for Nalidixic acid (NA) (up to 15%); and for Trimethoprime/Sulfamethoxazole (SXT) (up to 13%) and for Tetracycline (TE) (57%). Median values for E. coli in the inflow (crude sewage) of the plants were between 2.0 x 10(4) and 6.1 x 10(4)CFU/ml (Coli ID-agar, BioMerieux 42017) but showed a 200-fold reduction in all three plants in the effluent. Nevertheless, more than 10(2)CFU E. coli/ml reached the receiving water and thus sewage treatment processes contribute to the dissemination of resistant bacteria in the environment.

Anti-Bacterial Agents↗

Viscus perforation in peritoneal dialysis patients: diagnosis and outcome.

OBJECTIVE: To determine the incidence and outcome of spontaneous viscus perforation in peritoneal dialysis (PD) patients and which factors could facilitate early diagnosis. DESIGN: A retrospective chart review was done on all patients with viscus perforation and on a control group with peritonitis secondary to gram-negative organisms. SETTING: A tertiary care University Hospital Peritoneal Dialysis program. PATIENTS: All patients with surgically proven spontaneous viscus perforation from 1978 to June 1992 (n = 15). A group of control patients (n = 15) with gram-negative bacterial peritonitis was also reviewed for comparison. INTERVENTIONS: None. MAIN OUTCOME MEASURES: Hospital days, patient survival after perforation, and return to peritoneal dialysis were the main outcomes measured. Peripheral white blood cell (WBC) count, PD fluid WBC count with differential, PD fluid cultures, radiologic information, and surgical intervention were also evaluated. Data were analyzed using the Mann-Whitney test to determine significant differences between the two groups. RESULTS: Viscus perforation occurred in 15 of the 431 patients on PD from 1978 to June 1992 (3.5%). In comparison to the control group, patients with viscus perforation had a significantly higher peripheral WBC count (p = .016), a higher mean PD fluid WBC count (p = .006), and a higher mean percentage of polymorphonuclear cells in the PD effluent (p = .038). Multiple organisms on PD fluid cultures were noted in 12 of 15 patients with perforation and in only 3 control patients. Pneumoperitoneum was seen on abdominal or chest radiograph or computerized tomographic (CT) scan in 10 of 15 patients with perforation and in only 1 of 15 patients in the control group. All patients with viscus perforation required surgery and 6 expired. Only 1 death occurred in the control group. Only 1 of the 9 patients surviving perforation was able to resume PD, in contrast to 13 of 14 surviving control patients. CONCLUSION: We conclude that viscus perforation is associated with high morbidity, mortality, and technique failure. Diagnosis may be made by repeatedly searching for intraperitoneal free air on radiograph or CT scan in patients with persistently elevated peripheral and PD fluid WBC count, and for multiple organisms on PD fluid culture.

Adult↗

Pancreas transplantation. An initial experience with systemic and portal drainage of pancreatic allografts.

Pancreas transplantation has evolved dramatically since its introduction in 1966. As new centers for transplantation have developed, the evaluation of complications associated with pancreas transplantation has led to advances in surgical technique. Furthermore, surgical alterations of the pancreas resulting from transplantation (systemic release of insulin and denervation) are of unproven consequence on glucose metabolism. Since 1988, the authors have performed 21 transplants (16 combined pancreas/kidney, 3 pancreas alone, which includes 1 retransplantation, 1 pancreas after previous kidney transplant, and 1 "cluster") in 20 patients aged 18 to 49 years; mean, 35 +/- 1 years. Overall patient survival is 95%. Three pancreatic grafts failed within the first year because of technical failure; one additional pancreas was lost to an immunologic event on postoperative day 449, for an overall pancreatic graft survival of 81%. No renal grafts were lost. To evaluate causes of graft failure, demographic data were compared, which included age and sex of the donor and the recipient, operative time, intraoperative blood transfusion, and ischemic time of the graft. No statistically significant differences were found between groups except for ischemic time (11.7 +/- 6.4 hours for the technical success group versus 19.8 +/- 3.7 hours for the technical failure group; p less than 0.05 by unpaired Student's t test). Quadruple immunosuppression was used, which included prednisone, cyclosporine, azathioprine, and antilymphoblast globulin. A mean of 1.2 (range, 0 to 3) rejection episodes per patient occurred. Mean hospital stay was 24 +/- 11 days. Surgical and infectious complications were evaluated by comparing the technical success (TS) group (n = 17) with the technical failure (TF) group. Surgical complications in the TS group revealed a mean of 1.3 episodes per patient, whereas the TF group had 3.7 episodes per patient. The TS also had a reduced incidence of infectious complications compared with the TF (1.7 versus 4.3 episodes per patient). Cytomegalovirus was common in both groups, accounting for 11 infectious episodes, and occurred on a mean postoperative day of 38. Mean postoperative HbA1C levels dropped to 5 +/- 1% from 11 +/- 3%. The authors developed a new technique that incorporates portal drainage of the pancreatic venous effluent in three recipients. Preoperative metabolic studies disclosed a mean fasting glucose of 211 +/- 27 mg/dL and a mean stimulated glucose value of 434 +/- 41 mg/dL for all patients; the mean fasting insulin was 23 +/- 4 microU/mL.(ABSTRACT TRUNCATED AT 400 WORDS)

Adolescent↗

Occurrence and fate of the cytostatic drugs cyclophosphamide and ifosfamide in wastewater and surface waters.

The two oxazaphosphorine compounds cyclophosphamide and ifosfamide are important cytostatic drugs used in the chemotherapy of cancer and in the treatment of autoimmune diseases. Their mechanism of action, involving metabolic activation and unspecific alkylation of nucleophilic compounds, accounts for genotoxic effects described in the literature and is reason for environmental concern. The occurrence and fate of cyclophosphamide and ifosfamide were studied in wastewater treatment plants (WWTPs) and surface waters in Switzerland, using a highly sensitive analytical method based on solid-phase extraction and liquid chromatography tandem mass spectrometry. The compounds were detected in untreated and treated wastewater at concentrations of <0.3-11 ng/L, which corresponded well with concentrations predicted from consumption data and typical renal excretion rates. Weekly loads determined in influent and effluent wastewater were comparable and suggested a high persistence in WWTPs. Furthermore, no degradation was observed in activated sludge incubation experiments within 24 h at concentrations of approximately 100 ng/L. Processes that may be relevant for elimination in natural waterbodies were studied with a set of incubation experiments in the laboratory. After extrapolation to natural conditions in surface waters, a slow dark-chemical degradation (half-lives on the order of years) is the most important transformation process. Degradation by photochemically formed HO* radicals may be of some relevance only in shallow, clear, and nitrate-rich waterbodies but could be further exploited for elimination of these compounds by advanced oxidation processes, i.e., in a treatment of hospital wastewater. In surface waters, concentrations ranged from < or =50 to 170 pg/L and were thus several orders of magnitude lower than the levels at which acute ecotoxicological effects have been reported in the literature (mg/L range). However, due to a lack of studies on chronic effects on aquatic organisms and data on occurrence and effects of metabolites, a final risk assessment cannot be made.

Chromatography, Liquid↗

Chernobyl retrospective.

On April 28, 1986 heavy radioactive fallout from an unknown source was reported from Sweden. Later, it was discovered that two days earlier, a nuclear power reactor at Chernobyl, in the Soviet Union, had exploded releasing an enormous cloud of effluent containing 40 million Ci of 131I, 3 million Ci of 137Cs, and 50 million Ci of xenon radioisotopes. This far exceeded the 15 Ci of 131I escape in the notorious Three Mile Island accident. Chernobyl reactor IV, of an antiquated design, was a graphite-moderated reactor which suffered a steam explosion when the operating staff attempted an experiment involving preservation of safety functions during a planned shutdown. Following the explosion, a fire started in the graphite core which required ten days to control. Thirty-one persons died, two in the initial explosion and 29 of various combinations of thermal and radiation burns, and gamma irradiation. Existing emergency plans were invoked involving treatment on the scene and evacuation of seriously injured patients to a special hospital in Moscow, as well as to nearby Kiev. Later, 135,000 residents of the immediate neighborhood were surveyed and evacuated after fallout radiation levels began to rise. Fallout patterns around Europe and the northern hemisphere were closely tracked. Consequences of the accident in human and monetary terms will require years of evaluation. Although the United States has no power reactors of the Chernobyl type, the country does have a radiation disaster management plan, often rehearsed at the state level. As a consequence of Chernobyl certain international agreements dealing with radiation disaster information and management have been forged.

Accidents↗

Clinical biocompatibility of a neutral peritoneal dialysis solution with minimal glucose-degradation products--a 1-year randomized control trial.

BACKGROUND: Chronic utilization of a bio-incompatible peritoneal dialysis (PD) solution with acidic pH and a high content of glucose degradation product (GDP) has been implicated as a contributing cause of peritoneal failure. We compared a newly formulated solution of neutral pH and low levels of GDP to a standard PD solution. METHODS: Fifty new PD patients were randomized to a conventional lactate-buffered fluid (control) and a pH neutral, lactate-buffered, low GDP solution (balance). Patients were followed for 12 months. Serum samples were assayed for C-reactive protein (CRP). PD effluent was collected and assayed for cancer antigen-125 (CA125) and hyaluronan (HA). Clinical end points were the residual renal function and dialysis adequacy indices. RESULTS: After 52 weeks of treatment, PD fluid CA125 rose from 2.45 +/- 0.96 to 14.30 +/- 2.17 U/ml (P < 0.001), and HA declined from 2.26 +/- 0.60 to 1.45 +/- 0.32 mug/ml (P = 0.07) in the balance group. The balance group had a higher PD fluid CA-125 (14.30 +/- 2.17 vs 7.36 +/- 2.23 U/ml, P = 0.007), lower HA (1.45 +/- 0.32 vs 2.55 +/- 0.32 mug/ml, P = 0.007), and lower serum CRP level (1.77 +/- 0.42 vs 7.73 +/- 2.42 mg/l, P = 0.026) than the control group at 52 weeks. There was no difference in dialysis adequacy indices, ultrafiltration volume, urine output, residual renal function, peritonitis rate or need of hospitalization in 1 year. CONCLUSION: As compared to conventional PD solution, the use of balance, a neutral pH, low GDP solution resulted in a superior profile of PDE mesothelial cell marker and a lower degree of systemic inflammation, and the difference was maintained for 1 year. It remains to be determined whether these effects could result in better long-term clinical outcome.

Biomarkers↗

Peritoneal defense using icodextrin or glucose for daytime dwell in CCPD patients.

OBJECTIVE: To investigate peritoneal defense during icodextrin use in continuous cyclic peritoneal dialysis (CCPD). DESIGN: In an open, prospective, 2-year follow-up study, CCPD patients were randomized to either glucose (Glu) or icodextrin (Ico) for their long daytime dwell. SETTING: University hospital and teaching hospital. PATIENTS: Both established and patients new to CCPD were included. A life expectancy of more than 2 years, a stable clinical condition, and written informed consent were necessary before entry. Patients aged under 18 years, those who had peritonitis in the previous month, and women of childbearing potential, unless taking adequate contraceptive precautions, were excluded. Thirty-eight patients (19 Glu, 19 Ico) started the study. The median follow-up was 16 and 17 months for Glu and Ico respectively (range 0.5-25 months and 5-25 months, respectively). OUTCOME MEASURES: Peritoneal defense characteristics and peritoneal dialysis-related infections were recorded every 3 months. RESULTS: Total peritoneal white cell count tended to decrease over time in both groups. After 1 year, absolute numbers and percentages of effluent peritoneal macrophages (PMphis) were significantly higher in Ico than in Glu patients; this difference in the percentage persisted after 2 years. Percentage of mesothelial cells increased overtime in Ico patients. The phagocytic capacity of PMphis decreased over time, resulting in a borderline significant difference for coagulase-negative staphylococci (p = 0.05) and a significant difference for Escherichia coli (p < 0.05) phagocytosis in favor of Ico patients. PMphi oxidative metabolism remained stable over time without a difference between the groups. PMphi cytokine production and effluent opsonic capacity also remained stable over time. Finally, 16 peritonitis episodes in Glu and 14 in Ico patients occurred. Glucose patients had 37 and Ico patients 32 exit-site infections during the study. CONCLUSION: CCPD patients using Ico did equally as well as Glu-treated patients with respect to clinical infections and most peritoneal defense characteristics. However, in a few peritoneal defense tests, Ico-treated patients did better.

Adult↗

Microbial isolates in chronic osteomyelitis--a guide to management.

Between August 1995 and December 1999, sixty patients with chronic osteomyelitis had the effluent from the discharging sinuses and bone biopsies cultured aerobically and anaerobically. 47 positive isolates were obtained and the organism commonly isolated both in the single- and two-organism isolates was Staphylococcus aureus. The sensitivity patterns of these isolates were carried out with the available antibiotic discs. 30 per cent of the organisms isolated were sensitive to ceftriaxone (Rocephine) and gentamycin.

Anti-Bacterial Agents↗

A pseudoepidemic of Sporothrix cyanescens pneumonia occurring during renovation of a bronchoscopy suite.

Sporothrix cyanescens, an uncommonly isolated mold, was cultured from biopsy tissue, bronchial washings and sputum obtained at bronchoscopy from four patients during a one-month period. These patients had undergone fiberoptic bronchoscopy to aid in the diagnosis of pneumonic infiltrates. During this period of time the bronchoscopy suite was being extensively renovated. Cultures of bronchoscopes, biopsy forceps and effluents from the bronchoscopy injection ports were negative for fungi, as were all environmental samples taken from the bronchoscopy suite. Known pulmonary pathogens were eventually isolated from two of the patients and the pneumonias resolved in all four patients. It is believed that bronchoscopy material was contaminated by dust created during modernization of the bronchoscopy suite and that the four isolates represent a unique pseudoepidemic of S. cyanescens pneumonia.

Aged↗

Comparison of single- and multi-dose crystalloid cardioplegia to protect the immature myocardium.

The primary objective of this study was to compare the protective effects of single-dose and multi-dose St. Thomas' Hospital cardioplegic solution number 1 in the ischemic and reperfused neonatal rabbit heart. In addition, the effect of including bicarbonate (a component of St. Thomas' Hospital cardioplegic solution number 2) was also studied. Hearts (n = 8 per group) were excised from rabbits (7-10 days old) and aerobically perfused in the working mode with crystalloid media for 20 min (37 degrees C). After assessing cardiac function, the hearts were arrested by an infusion of cold cardioplegic solution (2 min at 15 degrees C) with or without the addition of bicarbonate (10 mmol). The hearts were then subjected to 6 h of hypothermic ischemia (15 degrees C) and, during this period, some hearts received multiple infusions (2 min/h at 15 degrees C) of cardioplegic solution. All hearts were reperfused for 35 min (15 min Langendorff plus 20 min working), cardiac function was then re-assessed and expressed as a percent of the preischemic value. The coronary effluent, collected during the first 15 min of reperfusion, was assayed for creatine kinase activity. At the end of the reperfusion period, the hearts were freeze clamped and taken for metabolic analysis. With multi-dose cardioplegia (without bicarbonate) the postischemic recovery of cardiac output was 67.0 +/- 6.5% and with single-dose the value was 39.3 +/- 10.0% (NS). The same pattern of postischemic recovery (that varied between 30% and 60%) for aortic flow, stroke volume and stroke work was observed with both multi-dose and single-dose infusion.(ABSTRACT TRUNCATED AT 250 WORDS)

Analysis of Variance↗

Effect of combining phosphodiesterase III inhibitors with St Thomas Hospital's solution used as transplantation preservative solution in isolated rat hearts.

Improved preservation of the harvested heart with attenuation of the reperfusion injury is important for successful outcomes of cardiac transplantations. The most commonly used cardioplegic solution, to prevent ischemic changes has been St Thomas' Hospital cardioplegic solution (STHCS). However, it is neither ideal nor sufficient to prevent myocardial ischemia and reperfusion injury. Phosphodiesterase inhibitors can attenuate the damage due to the injuries of ischemia and reperfusion. In this study we sought to enrich STHCS with a phosphodiesterase inhibitor to improve preservation of cardiac functions. The harvested hearts of 24 rats were divided into four groups. All hearts were mounted on a Langendorff perfusion system. After a stabilization period, cardiac arrest was maintained by STHCS. The hearts were stored in STHCS alone or with milrinone, amrinone, or enoximone for 6 hours. The reperfusion was maintained using a modified Tyrode's solution. All hearts were compared for their preischemic and postischemic left ventricular developed pressure, +dp/dtmax, -dp/dtmax, duration of systole, ejection time, and time to reach peak systolic pressure. Coronary effluent was collected for lactate dehydrogenase (LDH) measurements. The initial values for all metrics were comparable between the groups. During the postreperfusion period, all hearts showed lower peak systolic pressures than the initial values. Although the amrinone group seemed to have higher values, the 25-minute result was at the border of significance and the 30-minute value, significantly higher. All hearts showed far lower results of maximum changes in contractility during the time period (+dp/dtmax) versus the initial values; comparisons between groups were not significant. For the parameter of maximum changes in relaxation during the time period (-dp/dtmax), while other hearts showed lower results, the amrinone group displayed values comparable to the initial ones after 20 minutes. Comparisons between groups were insignificant. While other hearts had comparable values for time of systole, the hearts applied with milrinone reached these values after 15 minutes. Group comparison for time of ejection revealed that the results at 5-minute postreperfusion were higher in the enoximone and the amrinone groups than the milrinone group. Postreperfusion 5-minute results were higher in the enoximone and the amrinone groups than the milrinone group for time to reach peak systolic pressure. LDH levels were lowest in the amrinone group. In conclusion, our study revealed that adding phosphodiesterase inhibitors to STHCS improved peak systolic pressure and maximum changes in relaxation during the time period (-dp/dtmax, mm Hg/s). It also decreased the LDH leakage, which corresponded to the degree of ischemic tissue damage. Amrinone seemed to result in more favorable results, which may be attributed to its additional effects on inflammation, including those on cytokines and leukocyte aggregation.

3',5'-Cyclic-AMP Phosphodiesterases↗

NOx monitoring of a simultaneous nitrifying-denitrifying (SND) activated sludge plant at different oxidation reduction potentials.

Simultaneous nitrification-denitrification (SND) allows biological nitrogen removal in a single reactor without separation of the two processes in time or space but requires adapted control strategies (anoxic/aerobic conditions). In this study, the formation of gaseous nitric oxide (NO(G)) and nitrogen dioxide (NO(2G)) was monitored for SND in relation to the oxidation-reduction potential (ORP) and nitrogen removal in a lab batch reactor and a pilot membrane bio-reactor (MBR). In addition hospital wastewater (COD/N(tot)>6:1) was treated on site for 1 year. The highest total nitrogen removal rates of max 90% were reached at 220-240mV ORP (given as E(h)) with corresponding maximal NO(G) emissions rates of 0.9microgg(-1)VSSh(-1). The maximal emission rates of NO(2G) (0.2microgg(-1)VSSh(-1)) were reached at the same ORP level and the NO(2G) emissions correlated to the nitrite accumulation in the activated sludge up to 5mgl(-1)NO(2L)-N. It was shown that this correlation was due to biological production and not due to pH-dependent chemical conversion. Therefore, NO(2G) can be used as additional control loop for ORP-controlled SND systems to avoid the inhibition of denitrification and high nitrite concentrations in the plant effluent.

Bacteria, Aerobic↗

In vitro assessment of vancomycin HCl compatibility after coinfusion with a specialized amino acid formulation.

Vancomycin usage at British Columbia's Children's Hospital has increased substantially in the Special Care Nursery as a consequence of a study demonstrating a reduced morbidity and mortality in neonates with necrotizing enterocolitis when treated with vancomycin and cefotaxime. The inability to place more than one peripheral intravenous access necessitates interruption of parenteral nutrition to infuse vancomycin, resulting in a reduction of the planned daily intake of these neonates. This is clinically significant with the administration of vancomycin because of the long administration period required for this drug (60 minutes). This study was designed to assess the physical and chemical stability of vancomycin with a standard neonatal parenteral nutrition solution, Vamin A, when coadministered through the same intravenous line. To simulate the actual clinical setting, the dose of vancomycin and the infusion rate of Vamin A were chosen to represent those commonly used in a 1-kg neonate. Physical compatibility was assessed using effluent obtained after coinfusion of vancomycin with parenteral nutrition solution. Duplicate samples were visually checked for color changes and precipitate. High-pressure liquid chromatography (HPLC) and pH testing were used to assess chemical compatibility of vancomycin. The results of physical compatibility revealed no color change or precipitate. No changes in pH were observed. HPLC determination confirmed that there were no significant time-dependent changes in vancomycin stability. The samples were studied over 24 hours to determine the rate of degradation of vancomycin, if any, under various temperature conditions. The concentrations were not significantly different from each other at the different temperatures studied. Thus, there was no apparent change in the concentration of vancomycin in the presence of Vamin A.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acids↗

Preterm infants with high polyunsaturated fatty acid and plasmalogen content in tracheal aspirates develop bronchopulmonary dysplasia less often.

OBJECTIVE: Oxygen toxicity causes chronic bronchopulmonary dysplasia (BPD) in extremely preterm infants. Polyunsaturated fatty acids (PUFA) and plasmalogens are the two main substrates for lipid peroxidation in the pulmonary surfactant. In the present study, we tested whether low concentrations of both were associated with development of BPD and whether both were further reduced during mechanical ventilation with oxygen. DESIGN: Prospective, noninterventional, descriptive study. SETTING: Level III neonatal intensive care unit in a university hospital. PATIENTS: In 25 extremely low birth weight infants with respiratory distress syndrome, tracheal aspirates were collected immediately after birth and in the following 4 days. As control, tracheal and pharyngeal aspirates were collected from healthy infants immediately after birth. The amount of PUFA and dimethylacetals (DMA, representing plasmalogens) was determined gas-chromatographically. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The relative percentages of PUFA and DMA on all fatty acids in non-BPD infants (PUFA% 26+/-8.9, DMA% 3.5+/-1.2) were higher compared with infants who developed BPD (PUFA% 14.5+/-3.8, DMA% 1.8+/-0.9). In term healthy infants, DMA% and PUFA% were in the same range as in the BPD group. The higher levels found for non-BPD infants decreased after day 1 to values equal to the BPD group and remained low. CONCLUSIONS: The results suggest that initially higher levels of PUFA and plasmalogens in the tracheal effluent are associated with a reduced risk of developing BPD and are reduced during the first day of ventilation.

Bronchopulmonary Dysplasia↗

Environmental risk assessment of medicinal products for human use according to European Commission recommendations.

Presented here, based on new recommendations of the European Commission, is an environmental risk assessment (ERA) of a selected group of pharmaceuticals for Phase I, environmental exposure assessment, and Phase II Tier A, initial environmental fate and effect analysis. This pharmaceutical group is composed of the 111 highest-selling human drug substances that have annual sales in Germany of more than 5,000 kg. The data required for this ERA came from analyzing: (1) sales annually (in kg or IU) of the 2671 active pharmaceutical drug substances (2001) on the German market in all medicinal products sold by pharmacies (with and without prescriptions) and used in hospitals in 1996-2001; (2) the use pattern of drug substances as categorized according to Anatomical Therapeutic Chemical (ATC) classification indexes ATC3 and ATC7; (3) data for excretion, toxicity, and metabolites of the 111 selected human drug substances; (4) the physicochemical properties of these substances; and (5) the degradability of selected drug substances in sewage treatment plants (STPs) by using a validated and accredited liquid chromatography-electrospray ionization tandem mass spectrometry method. A correction factor for the pharmaceutical therapeutic (PT) activity of metabolites, the PT(Index) (excretion rate/100) for drug substances and PT active metabolites was established to refine the predicted environmental concentration (PEC(SURFACEWATER)). A refinement of the PEC(SURFACEWATER) was carried out with the market penetration factor of the human drug substances in Germany. In addition, for effect analysis the predicted no-effects concentration (PNEC) was calculated using assessment factors. The estimated PEC results were validated with the exposure results of effluents of the STPs. All results on ERA of drug substances have been documented in a Microsoft Access 2000 database.

Advisory Committees↗

Involvement of calcitonin gene-related peptide in nitroglycerin induced improvement of preservation with cardioplegic solution.

AIM: To study improvement of preservation with cardioplegic solution induced by nitroglycerin was related to stimulation of calcitonin gene-related peptide (CG RP) release. METHODS: The isolated rat heart was arrested using St Thomas Hospital cardioplegic solution and then was reperfused with normothermic Krebs-Henseleit solution for 40 min after the 4-h hypothermic ischemic period. Hear t rate, coronary flow, left ventricular pressure (LVP), and its first derivative (+/- dp/dtmax) were recorded, and the calcitonin gene-related peptide-like immunoreactivity (CGRP-LI) and the release of creatine kinase (CK) were measured. RESULTS: Nitroglycerin (0.1 or 1 micro;mol/L) or CGRP (5 or 10 nmol/L) caused an improvement of cardiac function (LVP and +/- dp/dtmax) and a decrease in the release of creatine kinase during reperfusion. The protection induced by nitroglycerin was abolished by CGRP(8-37), the selective CGRP receptor antagonist, or pretreatment wit h capsaicin to deplete sensory nerves neurotransmitter content, but was unaltered by treatment w ith glibenclamide, the blocker of the ATP-sensitive potassium channel (KATP). The protection induced by exogenous CGRP was not also blocked by glibenclamide. Levels of CGRP-LI in the coronary effluent were significantly increased in the hearts treated with nitroglycerin. However, the elevated level of CGRP-LI by nitroglycerin was abolished by pretreatment with capsaicin. CONCLUSION: The improvement of preservation with cardioplegic solution induced by nitroglycerin was related to stimulation of CGRP release in the rat heart, and the effect is not related to the activation of the KATP channel.

Animals↗

[Microbiological diagnosis of peritonitis in patients undergoing continuous ambulatory peritoneal dialysis. Review of 5 years at the Hospital de Galdakao].

BACKGROUND: With the aim of knowing the etiology of infectious peritonitis in patients undergoing continuous ambulatory peritoneal dialysis in our Hospital and the yield of our method of culture, we have made a revision of cases recorded during a five years period. METHODS: The peritoneal fluids of 105 patients with peritonitis was processed as following: 10 ml of uncentrifuged liquid was placed in hemocultures bottles, aerobe and anaerobe (Hemoline, Biomérieux) and incubated for up to 15 days at 37 degrees C. An additional 50 ml of peritoneal fluid was centrifuged and the sediment used for Gram stain and placed on enriched chocolate agar. Plates were incubated for up to two days at 37 degrees C in 5% of CO2. During the last year of the review the sediment of 50 ml resuspended in sterile distilled water was placed, too, in hemoculture bottles. In 18 cases we had only the hemoculture bottles inoculated by the nurse of the Nephrology Service (those patients came at a time when the laboratory was closed). Subcultures were identified with routine methodology. RESULTS: 96 (91.43%) of the 105 dialysis effluents processed were culture positive; 91.67% were bacterial and 8.33% fungal peritonitis. 64 (69.56%) of the bacterial isolates were Gram positive and 28 (30.43%) Gram negative. CONCLUSION: We remark the good yield of a simple culture method and the high rate of Gram negative and fungal peritonitis.

Ascitic Fluid↗

Peritoneal protein losses in children with steroid-resistant nephrotic syndrome on continuous-cycler peritoneal dialysis.

Glomerular protein permeability rises in nephrotic syndrome and may result from the effect of an unidentified "circulating factor." The effect of this "circulating factor" on the permeability of other body membranes is unknown. In this study we examine the peritoneal membrane protein permeability in patients with nephrotic syndrome on chronic-cycler peritoneal dialysis. We conducted a retrospective study of peritoneal protein losses in the dialysate effluent of 60 pediatric peritoneal dialysis patients (ages 5.1-22 years) over a 6-year period (January 1997-December 2002). Nineteen patients had steroid-resistant nephrotic syndrome (SRNS), while 41 had other non-nephrotic etiologies of renal failure. Total and normalized peritoneal protein losses are higher in SRNS than in non-nephrotic patients (12,603+/-5,403 mg/day vs 4,475+/-469 mg/day, P<0.05; 297.8+/-79.3 mg/kg per day vs 156.8+/-16.0 mg/kg per day, P<0.05; 9,614.6+/-3,253.4 mg/m(2) per day vs 4,168.3+/-367.3 mg/m(2) per day, P<0.05). The ratio of total protein in dialysate to plasma, a measure of peritoneal membrane protein permeability, was higher in SRNS patients (3.50+/-1.00% vs 0.68+/-0.06%, P<0.001). Serum albumin concentration was lower in SRNS patients (3.09+/-0.13 mg/dl vs 3.52+/-0.07 mg/dl, P<0.01). There were no differences between the two groups with regard to duration of peritoneal dialysis, dialysis prescription, numbers of peritonitis episodes, catheter replacements, or hospitalizations. In summary, these results demonstrate that peritoneal protein losses in patients with SRNS are twice as great as in those without nephrotic syndrome. These results are consistent with the systemic effect of a "circulating factor" in SRNS and underscore the importance of adequate protein intake in patients on peritoneal dialysis.

Adolescent↗