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Biomedical subjects

A Oliver

Publications and source records attributed to A Oliver.

At least 19 recordsLinked to original sources

Efficacy and potential for resistance selection of antipseudomonal treatments in a mouse model of lung infection by hypermutable Pseudomonas aeruginosa.

Hypermutable Pseudomonas aeruginosa strains are found with high frequency in the lungs of patients with chronic infections and are associated with high antibiotic resistance rates. The in vivo consequences of hypermutation for treatment in a mouse model of lung infection using strain PAO1 and its hypermutable derivative PAOdeltamutS are investigated. Groups of 30 mice were treated for 3 days with humanized regimens of ciprofloxacin (CIP), tobramycin (TOB), CIP plus TOB, or placebo, and mortality, total lung bacterial load, and 4x- and 16x-MIC mutants were recorded. The rates of mutation and the initial in vivo frequencies of mutants (at the onset of treatment) were also estimated and the in vitro- and in vivo-selected mutants characterized. Since both strains had identical MICs, the same pharmacokinetic/pharmacodynamic (PK/PD) parameters were obtained: area under the 24-h concentration-time curve (fAUC)/MIC = 385 for CIP and maximum concentration of drug in serum (fC(max))/MIC = 19 for TOB. Despite adequate PK/PD parameters, persistence of high bacterial numbers and amplification (50,000-fold) of resistant mutants (MexCD-OprJ hyperexpression) were documented with CIP treatment for PAOdeltamutS, in contrast to complete resistance suppression for PAO1 (P < 0.01), showing that conventional PK/PD parameters may not be applicable to infections by hypermutable strains. On the other hand, the efficacy of TOB monotherapy in terms of mortality reduction and bacterial load was very low regardless of the strain but not due to resistance development, since mutants were not selected for PAO1 and were only modestly amplified for PAOdeltamutS. Finally, the CIP-plus-TOB combination was synergistic, further reducing mortality and bacterial load and completely preventing resistance even for PAOdeltamutS (P < 0.01 compared to monotherapy), showing that it is possible to suppress resistance selection in infections by hypermutable P. aeruginosa using appropriate combined regimens.

Animals↗

Prognostic parameters other than Gleason score for the daily evaluation of prostate cancer in needle biopsy.

OBJECTIVE: To evaluate in prostate needle biopsies the usefulness and the efficacy of not time-consuming morphologic parameters in order to predict whether prostate cancer is organ-confined or it is not, that could contribute additional information to pre-surgical serum PSA and Gleason score, both of them parameters already accepted as clinically significant. METHODS: Three hundred and two consecutive patients were evaluated, of whom a diagnostic needle biopsy and the radical prostatectomy specimen with no pre-surgical hormone therapy were available. Bilateral or unilateral extension, number of positive cores, percentage of positive cores, intraprostatic perineural invasion (IPNI) and the presence of high-grade prostatic intraepithelial neoplasia (HGPIN) in any of the biopsy cores were evaluated in the needle biopsy. RESULTS: The median of cores is 6. The IPNI, the presence of bilateral tumour, and the percentage of positive cores, higher than 37.5% (ROC curve), show significant crude OR (4.0, 2.8, 6.9 respectively). The regression model discloses that only the percentage of positive cores shows a significant OR (5.8) adjusting for bilaterality, IPNI, HGPIN and age. CONCLUSIONS: The percentage of cores with cancer and the bilateral involvement are another two parameters predictive of cancer with extraprostatic extension. (p<0.0005 in both). IPNI has statistical significance too (p<0.002), but it is related to the tumour volume expressed through the two mentioned parameters.

Adult↗

A mechanism of lateral flexion distraction injury of the spine.

Flexion distraction fractures or Chance fractures are well described in the literature. We present an unusual pattern of injury of a pure lateral flexion distraction fracture of the T12 vertebra with no posterior element disruption following a blow to the right torso to a passenger in a road traffic accident. The diagnosis was made intra-operatively as the potential for this injury pattern following the described mechanism was not initially recognised. We suggest that this type of injury be suspected in any patient where a fulcrum has acted at any point around the torso.

Accidents, Traffic↗

A simple cardiovascular risk score can predict poor outcome in non-heart-beating donor renal transplantation.

A simple cardiovascular risk score used in our centre to plan cardiovascular work-up for renal transplantation can predict outcome in non-heart-beating donor (NHBD) renal transplantation. Patients in the higher-risk group, with a score of >12 of a maximum of 36 are likely to have a longer duration of delayed graft function, poorer glomerular filtration rate at 6 months, and inferior graft and patient survival, together with a relative rate of graft loss within 60 days of 4.514 (P = .019) and within 1 year of 3.511 (P = .036). Although a high cardiovascular risk score should not be regarded as a contraindication to NHBD transplantation, the score can be used to facilitate recipient selection.

Adult↗

A simple cardiovascular risk score can predict poor outcome in NHBD renal transplantation.

A simple cardiovascular risk score used in our center to plan cardiovascular workup for renal transplantation can predict outcome in non-heart-beating donor (NHBD) renal transplantation. Patients in the higher risk group, with a score of >12 out of a maximum of 36 are likely to have a longer duration of delayed graft function, poorer glomerular filtration rate at 6 months, and inferior graft and patient survival, together with an relative rate of graft loss within 60 days of >4 (P = .053). Although a high cardiovascular risk score should not be regarded as a contraindication to NHBD transplantation, the score can be used to facilitate recipient selection.

Adult↗

Post-renal transplantation weight gain: its causes and its consequences.

OBJECTIVE: A tendency to increased body mass index (BMI) occurs after renal transplantation. The objective of this study was to analyze the causes and consequences of this weight gain. METHODS: Two hundred twelve renal transplant recipients were divided into 3 groups according to the evolution of their BMI: BMI loss (group 1); BMI increase <10% (group 2); and BMI increase >10% (group 3). RESULTS: The mean BMI gain was 6.2%, weight gain was 3.9 kg, and BMI gain was 1.4 kg/m(2). The patients in group 3 were younger, but there were no other significant differences in gender, preoperative diabetes, acute rejection, or prior BMI. Blood pressure was similar in all 3 groups, but more group 3 patients needed antihypertensive treatment. A progressive increase in total and low-density lipoprotein (LDL)-cholesterol was also observed as patients showed increased BMI. No differences were observed regarding carbohydrate metabolism. Groups 1 and 3 showed a more unfavorable micro-inflammatory profile. The creatinine clearance level was better in group 3 compared with group 1. We found no differences regarding the number of nonfatal postoperative cardiovascular events.

Adult↗

Determining factors of the response to hyperhomocysteinemia treatment in renal transplant patients.

Hyperhomocysteinemia (hyperHcy) is a risk factor for cardiovascular disease. The benefits of lowering homocysteinemia (Hcy) in renal transplant recipients through vitamin treatment are not clearly understood. The objective of this study was to establish the demographic, renal, Hcy metabolism, and microinflammation factors that determined the response to folic acid and vitamin B complex treatment in stable patients with renal transplants and hyperHcy. We studied 65 renal transplant patients with baseline hyperHcy. The mean baseline Hcy level of these patients was 22.5 micromol/L. Following treatment it fell to 14.5 micromol/L, an overall reduction of 35.5%. Forty-one patients (63%) were classified as responders; the remainder (37%), nonresponders. A bivariance analysis suggested the only significant differences between responding and nonresponding patients were the pre-treatment Hcy level and the renal function level.

Adult↗

Factors involved in baseline hyperhomocysteinemia in renal transplantation.

Hyperhomocysteinemia (hyperHcy) is one cardiovascular risk. The objective of this study was to establish the prevalence demographic, and clinical and analytical factors related to hyperhomocysteinemia among renal transplant patients. The mean Hcy level was 17.3 micromol/L; the prevalence of hyperHcy was 61.2%. The population was categorized as hyperHcy and normal-homocysteinemia (Hcy) patients. Those subjects with hyperHcy were mostly men, with lower intraerythrocyte folate and vitamin B(12) levels, higher fibrinogen levels, and poorer renal function. Multivariate evaluation showed that creatinine clearance, plasma intraerythrocyte folate and vitamin B(12) levels, and plasma fibrinogen levels were independently associated with Hcy levels. Even though the Hcy level was slightly higher among patients who suffered a posttransplantation cardiovascular event, this was statistically significant.

Adult↗

Antimicrobial therapy for pulmonary pathogenic colonisation and infection by Pseudomonas aeruginosa in cystic fibrosis patients.

Pseudomonas aeruginosa colonisation has a negative effect on pulmonary function in cystic fibrosis patients. The organism can only be eradicated in the early stage of colonisation, while reduction of bacterial density is desirable during chronic colonisation or exacerbations. Monthly, or at least 3-monthly, microbiological culture is advisable for patients without previous evidence of P. aeruginosa colonisation. Cultures should be performed at least every 2-3 months in patients with well-established colonisation, and always during exacerbations or hospitalisations. Treatment of patients following the first isolation of P. aeruginosa, but with no clinical signs of colonisation, should be with oral ciprofloxacin (15-20 mg/kg twice-daily for 3-4 weeks) plus inhaled tobramycin or colistin (intravenous treatment with or without inhaled treatment can be used as an alternative), while patients with acute infection should be treated for 14-21 days with high doses of two intravenous antimicrobial agents, with or without an inhaled treatment during or at the end of the intravenous treatment. Maintenance treatment after development of chronic P. aeruginosa infection/colonisation (pathogenic colonisation) in stable patients (aged>6 years) should be with inhaled tobramycin (300 mg twice-daily) in 28-day cycles (on-off) or, as an alternative, colistin (1-3 million units twice-daily). Colistin is also a possible choice for patients aged<6 years. Treatment can be completed with oral ciprofloxacin (3-4 weeks every 3-4 months) for patients with mild pulmonary symptoms, or intravenously (every 3-4 months) for those with severe symptoms or isolates with ciprofloxacin resistance. Moderate and serious exacerbations can be treated with intravenous ceftazidime (50-70 mg/kg three-times-daily) or cefepime (50 mg/kg three-times-daily) plus tobramycin (5-10 mg/kg every 24 h) or amikacin (20-30 mg/kg every 24 h) for 2-3 weeks. Oral ciprofloxacin is recommended for patients with mild pulmonary disease. If multiresistant P. aeruginosa is isolated, antimicrobial agents that retain activity are recommended and epidemiological control measures should be established.

Amikacin↗

Contribution of clonal dissemination and selection of mutants during therapy to Pseudomonas aeruginosa antimicrobial resistance in an intensive care unit setting.

Rates of antibiotic resistance in Pseudomonas aeruginosa isolates from intensive care unit (ICU) patients are expected to be dependent on the selection of resistance mutations during therapy, the availability of exogenous resistance determinants and their dissemination potential, and the efficiency of transmission of the resistant strains. The relative contributions of these three factors were studied in an ICU with no apparent outbreak in 216 sequential P. aeruginosa isolates recovered from 102 patients between September 2002 and November 2003. Analysis of pulsed-field gel electrophoresis patterns revealed the presence of 82 different clones. Thus, the dissemination of particular resistant clones had a minimal effect on the relatively high overall resistance frequencies found for imipenem (32%), cefepime (25%), ceftazidime (24%), meropenem (22%), ciprofloxacin (18%) and tobramycin (2%). Rates of primary resistance were relatively low, and resistance development during treatment (secondary resistance) was the main factor contributing to the overall high resistance rates. In ICU settings with a low prevalence of epidemic resistant strains, the main strategy for resistance control should focus on the design of targeted regimens to avoid the development of resistance.

Anti-Bacterial Agents↗

Trace element concentrations in patients on home enteral feeding: two cases of severe copper deficiency.

BACKGROUND: Enteral feeding is the fastest growing area of artificial nutrition, with the annual rate of growth being estimated at 20-25% a year. Previous studies have demonstrated trace element deficiencies in patients on long-term home enteral nutrition (HEN). METHODS: The trace elements zinc, selenium, copper and manganese were measured in blood samples from 37 patients on HEN using atomic absorption spectroscopy. RESULTS: Plasma zinc concentrations (range 7.4-14.4 micromol/L) were below the reference range (12.6-22.0 micromol/L) in 30 patients, plasma selenium concentrations (range 0.73-1.76 micromol/L) were below the reference range (0.8-2.0 micromol/L) in only one patient. Whole blood manganese (range 74-309 nmol/L) and plasma manganese (range 13-51 nmol/L) were above both respective reference ranges (73-210 nmol/L and 9-24 nmol/L) in four patients. Two patients showed severely low plasma copper concentrations of 2.4 micromol/L and 2.5 micromol/L, and responded to treatment with extra copper supplementation. CONCLUSION: Although enteral feeds contain adequate concentrations of trace elements, problems with bioavailability may occur and patients receiving long-term enteral feeding should be monitored with regard to plasma trace element concentrations.

Adult↗

[Proteinuria and chronic renal failure in the coast of El Salvador: detection with low cost methods and associated factors].

OBJECTIVES: El Salvador has high mortality rates from chronic kidney disease (CKD). The actual prevalence and causes remain unknown and local resources are scarce. Previous studies have suggested very high prevalence in specific populations: adult male farmers living in the coastlands, with high frequency of pesticides exposure and alcohol consumption. This population has low incomes and poor healthcare accessibility. Our aim was to detect CKD cases in this population using proteinuria as an inexpensive initial screening, investigating associations with those characteristics and comparing them with another population from the midlands. METHODS: We performed a transversal study on volunteer men from both regions, taking into consideration the variables: age, farmer living, pesticides, exposure, alcohol consumption, medical past history, blood pressure level, glycemia and proteinuria in a random urine sample. Coastland men with proteinuria were additionally screened for CKD measuring hemoglobin and serum creatinine levels. Finally, we employed a logistic regression model, and Perason's Chi2 to investigate associations between those variables and the presence of proteinuria or CKD. RESULTS: We included 291 men from the coastlands and 62 from the midlands: 35 and 16% off the total male population from their respective communities. Proteinuria (table I) was found in 133 (45.7%) and 8 cases (12.9%). CKD was diagnosed in 37 (12.7%) coastland men (table III), with mean creatinine 2.64 +/- 2.5 mg/dl, hemoglobin 12.32 +/- 1.9 g/dl and 81.1% with proteinuria 15-30 mg/l. Only 14 (37.8%) out of those 37 CKD patients featured diabetes or hypertension, while the remaining (62.2%) did not appear to have a clear-cut cause for CKD. Only one of them was formerly diagnosed with CKD. Farmer living, pesticides exposure and alcohol consumption were found to be very common characteristics in both populations, and were not associated to the presence of proteinuria or CKD (table II and III) DISCUSSION: The prevalence of CKD within the adult male farmers from the Salvadoran coastlands is remarkably high: at least 12.7%. There is a large number of undiagnosed cases, but they can be easily detected with inexpensive methods. This high prevalence is not completely explained by usual CKD causes like diabetes or hypertension. In addition, pesticides exposure and alcohol consumption may not be related, too. The disease is moderate, non symptomatic and has fairly mild proteinuria, possibly from interstitial origin. Further research is required to investigate environmental, occupational and hereditary factors, and to determine the real extent of the problem.

Adult↗

Epidemiological relatedness of methicillin-resistant Staphylococcus aureus from a tertiary hospital and a geriatric institution in Spain.

From January 2000 to June 2002, 24 Staphylococcus aureus isolates were recovered from decubitus ulcers of patients in a geriatric institution, of which 17 (70.8%) were methicillin-resistant S. aureus (MRSA). Antibiotic resistance and DNA macrorestriction (pulsed-field gel electrophoresis; PFGE) patterns of the MRSA isolates were compared with a collection of 161 MRSA isolates from patients admitted to the institution's reference hospital. PFGE revealed the presence of five clonal types (found also in hospitalised patients) among the 17 MRSA isolates. The findings suggest nosocomial acquisition of the MRSA strains by five patients, with subsequent dissemination of the strains within the institution. The high rate of MRSA highlights the need for epidemiological analysis to control the dissemination of MRSA in long-term care facilities.

Aged↗

Low risk of contrast nephropathy in high-risk patients undergoing spiral computed tomography angiography with the contrast medium iopromide and prophylactic oral hydratation.

BACKGROUND: Spiral computed tomography angiography (CTA) is a sensitive and specific technique for visualizing renal arteries and diagnosing renal artery stenosis (RAS). Whether spiral CTA is associated with increased risk of contrast nephropathy (CN) in patients with impaired renal function is unknown. METHODS: We prospectively studied 50 patients with chronic renal insufficiency (serum creatinine concentration greater than 1.58 mg/dl) who underwent spiral CTA with iopromide, a nonionic, low-osmolar contrast agent. Fourteen patients had diabetes mellitus. Patients were encouraged to drink 1 l of water 12 hours before and 2 l over 24 hours after the procedure. The presence of CN was defined by an increase of 20% or more in the baseline serum creatinine level within or 72 hours after administration of the radio-contrast agent. RESULTS: In the entire group, mean serum creatinine levels increased significantly from 2.92 +/- 1.39 to 3.06 +/- 1.55 mg/dl (p = 0.02) and mean creatinine clearance decreased from 29.8 +/- 12.9 to 28.9 +/- 12.8 ml/min (p = 0.009) 72 h after administration of the contrast medium. Two patients experienced an increase in serum creatinine level of 20%. Renal function returned to baseline within seven days in the 2 patients. Absolute changes in creatinine clearance after the administration of radiocontrast medium were similar in nondiabetic and diabetic patients and in the subgroup of patients, with a baseline serum creatinine of < 3 mg/dl and > or = 3 mg/dl. CONCLUSIONS: In patients with chronic renal insufficiency, spiral CTA performed with iopromide, a nonionic, low-osmolar contrast medium and a prophylactic oral hydratation, is a minimally invasive technique with low risk of contrast nephropathy.

Aged↗

Risk of ischemic stroke associated with functional thrombin-activatable fibrinolysis inhibitor plasma levels.

BACKGROUND AND PURPOSE: Recently, a novel procarboxypeptidase B-like proenzyme, called thrombin-activatable fibrinolysis inhibitor (TAFI), has been described. It plays an important role in the delicate balance between coagulation and fibrinolysis. TAFI leads to potent inhibition of tissue plasminogen activator-induced fibrinolysis. The relevance of TAFI in thromboembolic disease is unclear. We have investigated the risk of ischemic stroke (IS) in relation to plasma levels of functional TAFI. METHODS: In a case-control study, we enrolled 264 individuals; 114 had IS, and 150 were recruited as controls who were age and sex matched and had no history of arterial disease. The individuals supplied information on their personal and family histories of cardiovascular diseases and conventional cardiovascular risk factors. Functional TAFI assays were performed by use of a method based on the activation of TAFI with thrombin-thrombomodulin and the measure of the TAFI activity generated. Other hemostatic parameters assayed were factor VIIIc, anti-phospholipid antibodies,fibrinogen, factor V Leiden, and the prothrombin gene G20210A mutations (PT20210A). RESULTS: Functional TAFI levels were significantly higher in patients with IS (113.7+/-25%; range, 57% to 209%) than in controls (102.6+/-19%). The odds ratio for IS in patients with functional TAFI levels >120% was 5.7 (95% confidence interval, 2.3 to 14.1). CONCLUSIONS: We found that functional TAFI levels in plasma (>120%) increased the risk of IS approximately 6-fold. Further studies should elucidate the physiological role of TAFI in arterial disease and possibly provide clues to therapeutic approaches.

Adult↗