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Biomedical subjects

J A Lorente

Publications and source records attributed to J A Lorente.

At least 37 records · Page 2Linked to original sources

Hemodynamic, biochemical and morphological changes induced by aminoguanidine in normal and septic sheep.

OBJECTIVE: To define the acute hemodynamic, metabolic, and morphological changes induced by aminoguanidine, a selective iNOS inhibitor, in septic sheep. DESIGN: Prospective, nonrandomized animal study. SETTING: Animal research facility in a University Hospital. INTERVENTIONS: Adult sheep, sedated and mechanically ventilated, were monitored with a pulmonary arterial catheter and an ultrasonic blood flow probe in the mesenteric artery, to measure the systemic (Q(TOT)I) and the mesenteric (Q(MES)I) blood flow indices, and an ileal tonometer. Four groups of sheep were studied: nonseptic, septic, nonseptic treated with aminoguanidine, and septic treated with aminoguanidine (100 mg kg(-1) h(-1)) (n = 6 for each group). Sepsis was induced by the intravenous administration of E. coli. Hemodynamic and biochemical parameters were measured during 300 min. Histological changes in the liver and small intestinal mucosa were analyzed at the end of the experiment. MEASUREMENTS AND MAIN RESULTS: In nonseptic animals, aminoguanidine slightly increased mean systemic arterial pressure (MAP), decreased Q(TOT)I, and increased vascular resistance index (SVRI) and pulmonary vascular resistance index. Q(MEs)I did not change and Q(MES)I/Q(ToT)I increased. Aminoguanidine also induced intestinal intramucosal hypercarbia, hyperlactatemia, acidemia, hypoglycemia, and morphological signs indicative of tissue ischemia in the small intestinal mucosa. In septic sheep, aminoguanidine increased SVRI and MAP only at 4 h after the septic challenge and thereafter, and worsened gas exchange. CONCLUSIONS: In this model, exogenous administration of aminoguanidine induces beneficial hemodynamic effects 4 h after the septic challenge. In normal animals, however, aminoguanidine was associated with hypoglycemia, acidosis, hyperlactatemia, and intestinal mucosal ischemia.

Acidosis↗

Lectinhistochemical and cytometrical evaluation of the corpus luteum of the rat at the end of pregnancy.

Most studies on the biochemistry and structure of the corpus luteum have focused on elucidating the processes of progesterone synthesis and release. In the present work, the histochemical composition of the corpus luteum of the rat was evaluated using lectinhistochemistry on rats at the end of pregnancy (days 18-23). We also analysed the morphology of the luteal cells, to characterize the changes attributable to regression in this organ. Seven biotinylated lectins were used (CON-A, WGA, DBA, SBA, PNA, RCA and UEA-I) following pre-set protocols (ABC method). The average diameter and area of the cells and their nuclei were measured. High reactivity of the luteal cells was observed with CON-A and a lower reactivity with WGA. The capillary endothelium gave positive reactivity with WGA and to a certain extent with SBA, PNA and RCA. Vesicular structures were intensely stained with DBA, and were more abundant in sections from animals with more advanced pregnancy, which could be attributable to cellular debris, on the basis of their morphologic characteristics. There were no significant differences among the cytometric variables analysed in comparisons of the values corresponding to the different days of gestation. These observations, together with previous research, suggest that, on the day of delivery, the corpus luteum of the rat is in the very early stages of structural regression, with no changes at the morphological level, but with changes at the molecular level.

Animals↗

Systemic hemodynamics, gastric intramucosal PCO2 changes, and outcome in critically ill burn patients.

OBJECTIVES: To define the hemodynamic and gastric intramucosal PCO2 (PiCO2) changes during the first 48 hrs after burn trauma and to analyze their relationship with outcome. DESIGN: Prospective, observational study in a cohort of consecutively admitted critically ill burn patients. SETTING: Intensive care burn unit in a university hospital. PATIENTS: Forty-two patients with burns covering >20% of body surface area or inhalation injury. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Patients were monitored with an oximetric pulmonary arterial catheter and a gastric tonometer to measure PiCO2. The difference between arterial and gastric mucosal PCO2 (P[i-a]CO2) was considered indicative of gastric mucosal hypoxia. Hemodynamic and PiCO2 measurements were performed during the first 48 hrs after admission. Patients suffered burns covering 36.1% +/- 14.3% (mean +/- SD) and 45.3% +/- 21.9% of body surface area (survivors and nonsurvivors, respectively). All patients were successfully resuscitated by conventional standards. Nonsurvivors (n = 16) died a median of 17 days after admission. In univariate analysis, the presence of shock during the resuscitation phase, age, mixed venous pH, P[i-a]CO2, right atrial pressure, pulmonary arterial pressure, pulmonary arterial occlusion pressure, cardiac index, systemic and pulmonary vascular resistance, left ventricular stroke work index, mixed venous oxygen saturation, and systemic oxygen delivery, consumption, and extraction ratio, measured over the first 12 hrs after admission, were significantly (p < .05) different between survivors and nonsurvivors. These differences disappeared after 12 hrs after admission. Multivariate analysis identified age, percentage body surface area burned, and oxygen delivery index (6 hrs after admission) as factors independently associated with a poor outcome. P[i-a]CO2 (12 hrs after admission) was significantly greater in patients with than in those without inhalation injury (17 +/- 13 torr [2.26 +/- 1.73 kPa] vs. 6 +/- 10 torr [0.79 +/- 1.33 kPa]; p = .005). Patients with a P[i-a]CO2 difference (6 hrs after admission) > or =10 torr (1.33 kPa) had a mortality rate of 56% vs. 25% of those patients with <10 torr (p = .044). CONCLUSIONS: Our data indicate that there are hemodynamic and biochemical changes that occur early after burn trauma that are associated with prognosis after an apparently successful resuscitation. Particularly, a hemodynamic profile characterized by systemic acidosis, low systemic blood flow, and systemic and pulmonary vasoconstriction early after trauma is associated with a poor outcome. Additionally, intestinal mucosal acidosis occurs after burn trauma, is influenced by inhalation injury, and is a variable related to outcome.

Adolescent↗

Treatment of toxic epidermal necrolysis with cyclosporin A.

BACKGROUND: Toxic epidermal necrolysis (TEN) is a severe skin disorder characterized by separation of the dermal-epidermal junction, as is observed in second-degree superficial burns. It has been proposed that immunosuppressive treatment may improve prognosis of patients with TEN. METHODS: We report here a case series of patients with TEN treated with cyclosporin A (CSA) without other concomitant immunosuppressive agent. These patients (n = 11) were consecutively admitted to our Intensive Care Burn Unit because of severe TEN, involving a large body surface area (83 +/- 17% [mean +/- SD], median, 90%; range, 35-96%) and were treated with CSA 3 mg/kg per day enterally every 12 hours. We compared the series of patients treated with CSA with a historical series of patients admitted to our Intensive Care Burn Unit before CSA was introduced as part of the treatment protocol These patients (n = 6) were treated with cyclophosphamide (150 mg i.v. every 12 hours) and different doses of corticosteroids (> or =1 mg/kg per day of 6-methyl-prednisolone). Both groups of patients were similar in regard to age, delay from onset of disease to Intensive Care Burn Unit admission, and body surface area involved. RESULTS: Time from the onset of skin signs to arrest of the disease progression (1.4 +/- 0.3 days, vs. 3.6 +/- 1.5 days) and to complete reepithelialization (12.0 +/- 3.6 days, vs. 17.6 +/- 3.1 days) was significantly shorter in patients treated with CSA compared with those treated with cyclophosphamide and corticosteroids (p = 0.0002, and p = 0.0058, respectively). Significantly fewer patients in the CSA group had > or =4 organs failing (2 of 11 vs. 3 of 6, respectively, p = 0.029), had severe leukopenia (<1,000 cells/microL) (0 of 11 vs. 4 of 6, respectively, p = 0.006), or died (3 of 6 vs. 0 of 11, respectively, p = 0.0029). CONCLUSION: We conclude that immunosuppressive treatment with CSA is safe and is associated with a rapid reepithelialization rate and a low mortality rate in patients with severe TEN. Our data suggest that this regimen could be more effective than treatment with cyclophosphamide and corticosteroids. Prospective controlled trials are required to test the hypothesis that CSA is more effective than cyclophosphamide or other immunosuppressive regimens for the treatment of TEN.

Adult↗

Serum bone alkaline phosphatase levels enhance the clinical utility of prostate specific antigen in the staging of newly diagnosed prostate cancer patients.

The aim of this study was to analyse the clinical utility of serum bone alkaline phosphatase (BAP) in addition to prostate-specific antigen (PSA) in the staging of newly diagnosed untreated prostate cancer patients. A prospective study was conducted, analysing serum BAP and PSA concentrations in 295 consecutive newly diagnosed untreated prostate cancer patients (T1-4, N0-1, M0-1b), 93 of whom had bone metastases on bone scan. The relationship of each marker with extent of bone disease, the influence of several clinical variables on both serum marker levels, the efficiency in predicting bone metastasis through receiver operating characteristic curves and, finally, the clinical utility in avoiding unnecessary bone scans were determined. Significant differences were found in the serum levels of both BAP and PSA between patients with and patients without bone metastases. Multiple regression analysis showed the extent of bone disease to be the only variable that influenced both serum levels. However, while serum BAP levels showed a statistical relationship with extent of bone disease, serum PSA levels did not. The best prediction of bone scan findings was obtained with the combination of both markers using a cut-off of 20 ng/ml, with positive and negative predictive values of 46.5% and 100%, respectively. This greater efficiency could permit 32.2% of initial bone scans to be avoided. False-positive and false-negative rates of BAP were 7.5% and 14%, respectively. This study suggests that serum BAP levels could play a complementary role in the diagnosis of bone metastasis in prostate cancer patients. This marker could provide useful clinical information on the degree of skeletal metastasis and constitute an easy way of enhancing the clinical utility of PSA. The addition of this marker to PSA in the initial evaluation could permit staging bone scan to be avoided at a PSA range of 10-20 ng/ml, with significant implications for cost saving.

Aged↗

Spinal cord injury after electrical trauma treated in a burn unit.

OBJECTIVE: To analyse the incidence, diagnosis and outcome of spinal cord injury in patients with electrical injuries. PATIENTS AND METHODS: Retrospective analysis of patients with electrical injuries admitted to our Intensive Care Burn Unit over a 5 year period. Among 435 admissions, 57 (13.1% of all admissions) were electrical injuries, due to either electrical flash (n = 34) or high voltage (n = 23). Two cases (8.6% of high voltage injuries) presented signs of spinal cord injury. Both cases presented an acute transverse myelopathy, involving the pyramidal tract, the posterior cords and the spinothalamic tract, causing a pyramidal syndrome with abnormal sensation and involvement of posterior cords, one with paraplegia and the other one with quadriplegia. Diagnoses were made 1 and 2 weeks after admission, respectively, when sedation was discontinued and neurological signs could be appreciated. Computerised axial tomography and nuclear magnetic resonance were normal in both cases at the moment of diagnosis. Both patients experienced a slow but progressive improvement of their neurological condition, and remain presently in a rehabilitation program 15 and 18 months after trauma. DISCUSSION: Our cases illustrate (i) that damage to the spine is not infrequent after electrical injury, (ii) the difficulty in making the diagnosis of spinal cord injury after electrical trauma, and (iii) the importance of early diagnosis to define neurological prognosis and start available therapies as soon as possible.

Adolescent↗

Modulation of systemic hemodynamics by exogenous L-arginine in normal and bacteremic sheep.

OBJECTIVE: To investigate whether exogenous L-arginine, the substrate for nitric oxide synthase, modulates systemic hemodynamics in sepsis. DESIGN: Prospective, controlled study in a sheep model of sepsis. SETTING: Animal research facility in a university hospital. SUBJECTS: Adult sheep weighing between 35 and 55 kg. INTERVENTIONS: Adult sheep sedated and mechanically ventilated, were monitored with a pulmonary arterial catheter and an ileal tonometer. Four groups of sheep were studied: nonseptic, septic, nonseptic treated with L-arginine, and septic treated with L-arginine. Sepsis was induced by the intravenous administration of Escherichia coli (1.5x10(8) colony-forming units/kg for 30 mins). L-arginine was administered as an intravenous bolus (200 mg/kg for 10 mins) before the septic challenge followed by 200 mg/kg/hr for 300 mins. MEASUREMENTS AND MAIN RESULTS: Sepsis induced a state of acidosis, hyperlactatemia, hypoxemia, and gastric intramucosal acidosis. During the first 30 mins after the septic challenge, there was a decrease in cardiac index and blood pressure, and an increase in systemic vascular resistance. Thereafter, blood pressure returned to baseline values, and systemic vascular resistance fell. Treatment with L-arginine in nonseptic sheep did not induce any biochemical or hemodynamic effect. In septic sheep, treatment with L-arginine was associated with a greater increase in systemic vascular resistance during the first 30 mins, and a more marked decrease in blood pressure and systemic vascular resistance after 180 mins. CONCLUSIONS: Exogenous administration of L-arginine does not induce hemodynamic effects in normal animals, exacerbates the acute vasoconstriction associated with the intravenous infusion of E. coli and potentiates the sepsis-induced vasodilation. Our results suggest that a) nitric oxide production is not constitutively modulated by exogenous L-arginine, b) L-arginine probably enhances the sepsis-induced sympathetic discharge, and c) L-arginine becomes rate-limiting for the formation of nitric oxide at approximately 3 hrs after the initiation of the septic challenge.

Acidosis↗

Intraindividual variations of total and percent free serum prostatic-specific antigen levels in patients with normal digital rectal examination.

PURPOSE: To analyze intraindividual variations of total and percent free serum prostate-specific antigen (PSA) in patients with normal digital rectal examination. MATERIAL AND METHODS: Total and free serum PSA were determined in two blood samples corresponding to 107 nonconsecutive patients. The period between both determinations ranged from 23 to 60 days. Prostatic biopsy was done after both determinations in all except 17 patients because the two serum PSA concentrations were <4 ng/ml. Total and free PSA were determined using double monoclonal antibody immunoassay Tandem and Tandem free (Hybritech Inc.). The diagnosis was benign prostatic hyperplasia (BPH) in 63 patients and prostate cancer (PCA) in 44. RESULTS: The variations of PSA ranged between -6.8 and +3.2 ng/ml in BPH patients and between -2.8 and +9.0 in patients with PCA. The median coefficients of variation were 15.4 and 15.7% respectively. The variations in the percent free PSA were between -30.7 and +40.9 in the BPH group and between -17.9 and +15.8 in the PCA group. The median coefficients of variation were 32.2 and 32.3% respectively. If prostatic biopsy had been indicated when percent free PSA had been </=25 in the PSA range of 4.1-10 ng/ml, we would have found discrepancies in 15% of all the patients. The sensitivity for the first determination would have been 100 and 94.4% for the second. The rate of negative biopsies would have been reduced by 16.6 and 19. 4% respectively. CONCLUSIONS: Intraindividual variations in serum PSA concentration and percent free PSA could have clinical implications in the decision to perform prostatic biopsy.

Aged↗

A randomized and controlled trial of the effect of treatment aimed at maximizing oxygen delivery in patients with severe sepsis or septic shock.

OBJECTIVE: To evaluate the effects of increased oxygen delivery on mortality and morbidity. DESIGN: Randomized, controlled trial. SETTING: Medical-surgical ICU of a tertiary care hospital. PATIENTS: Sixty-three patients classified according to predetermined criteria as having severe sepsis or septic shock. INTERVENTIONS: The patients were randomly assigned to one of two groups: the control group (n = 32) received conventional therapy with a normal targeted value of oxygen delivery, and the treatment group (n = 31) received therapy with a targeted oxygen delivery index (DO2I) value of > 600 mL/min/m2. The therapeutic approach to maintain BP, arterial saturation, hemoglobin concentration, and pulmonary artery occlusion pressure was similar in both groups. MEASUREMENTS AND MAIN RESULTS: The hemodynamic, oxygen transport, and gastric intramucosal pH measurements were recorded at the time of admission to the study and every 6 h for the next 96 h. The outcome measures were the rate of patient mortality and the number of organ dysfunctions occurring during the ICU stay. The study groups were similar with respect to demographics and admission hemodynamic variables, but the percentage of patients with positive blood cultures was significantly higher in the control group than in the treatment group, respectively: 34 vs 13% (p = 0.04). The average cardiac index was significantly higher in the treatment group than in the control group, respectively: 3.96 vs 3.05 L/min/m2 (p = 0.01). This factor did not significantly affect the DO2I. Nine of the 31 treatment group patients reached an average DO2I value of > 600 mL/min/m2. The rate of mortality in the control group patients up to the time of ICU discharge (66%) was similar to that seen in the treatment group (74%), respectively: 21 of 32 vs 23 of 31 (p = 0.46). The number of dysfunctional organs per patient was also similar in the control and treatment groups, respectively: 2.1+/-1.1 vs 2.6+/-1.2 (p = 0.12). CONCLUSION: Treatment aimed at maximizing oxygen delivery in patients with severe sepsis or septic shock does not reduce mortality or morbidity.

Aged↗

Spanish population data on the loci D13S317, D7S820, and D16S539 generated using silver staining (SilverSTR III Multiplex).

A set of 212 samples from unrelated Spanish Caucasians living in Andalucia (southern Spain) were analyzed with a new commercially-available kit for multiplex amplification of 3 STR loci (D13S137, D7S820, and D16S539), manual denaturing polyacrylamide gel electrophoresis and silver staining. These three loci are of special interest for the forensic community since they are a part of the 13 CODIS-core STR loci. The results show that the loci D13S317 and D16S539 meet Hardy-Weinberg expectations (HWE), but the locus D7S820 did not meet HWE (p = 0.003). However, there was no detectable departures from independence (i.e., linkage disequilibrium) between any pair-wise combination of loci. The D7S820 data were further investigated. The excess homozygosity was due to an excess of D7S820 10, 10 homozygotes. To determine if the allele frequency data are meaningful and can be applied to forensic identity cases, the Spanish D7S820 allele frequency data were compared with four other Caucasian sample populations. The D7S820 allele frequencies were statistically similar; thus, the results support that the allele frequency data can be used reliably for estimating DNA profile frequencies.

Alleles↗

Fluorescent multiplex analysis of nine STR loci: Spanish population data.

A total of 171 Caucasians living in Andalucia (southern Spain) have been typed for nine short tandem repeat (STR) loci by multiplex PCR amplification using a commercially available kit (Profiler Plus; Perkin-Elmer, Norwalk, CT, USA) and semi-automatic electrophoresis (ABI Prism 377 DNA Sequencer, Applied Biosystems, Foster City, CA, USA). The kit enables typing of the STR loci D3S1358, VWA, FGA, D5S818, D13S317, D7S820, D8S1179, D21S11, and D18S51. All loci, except D7S820, meet Hardy-Weinberg equilibrium. Because of the large number of loci that can be analyzed, the power of discrimination (PD) is greater than 0.99999, and the probability of exclusion (PE) reaches 0.99991 in our population sample.

Alleles↗

Degree of hypercoagulability and hyperfibrinolysis is related to organ failure and prognosis after burn trauma.

Severely burned patients often present a hypercoagulability situation. However, its magnitude, time course, and relationship with organ failure and outcome remains to be established. Forty-three patients were studied on the first and seventh day after burn for hypercoagulability and fibrinolysis parameters. A hypercoagulability and hyperfibrinolysis state was found the first day after burn demonstrated by high levels of activated factor VII (VIIa, p<0.01), thrombin-antithrombin III complex (TAT, p<0.01), tissue plasminogen activator (t-PA, p<0.001) and D dimer (DD, p<0.01) and low levels of antithrombin III (ATIII, p<0.01), protein C (PC, p<0.01), plasminogen (PG, p<0.001) and alpha2 antiplasmin (AP, p<0.001). A paradoxical coexisting hypofibrinolysis was found as suggested by a low global fibrinolytic activity in the euglobulin plasma fraction fibrin plate assay (FA, p<0.01) and high levels of tissue plasminogen activator inhibitor type 1 (PAI-1, p<0.01). On day 7, a less marked hypercoagulability situation was found, with low ATIII (p<0.01) and PC (p<0.01), persisting the hypofibrinolytic situation observed on the first day. Non-survivors (NS) showed higher levels of VIIa (p<0.01), TAT (p<0.05) and t-PA (p<0.05), and lower levels of ATIII (p<0.05), PC (p<0.05) and AP (p<0.001) than survivors (S) on the first day. Also, there was a positive correlation of Marshall organ failure score with ATIII, (r2=0.49, p<0.001), PC, (r2=0.14, p<0.045) and PG levels, (r2=0.41, p<0.0003). Severely burned patients show a state of transient disseminated intravascular coagulation, related to the development of organ failure and outcome.

Adult↗

Surgical treatment of extensive skin necrosis secondary to purpura fulminans in a patient with meningococcal sepsis.

Meningococcal sepsis is associated with a high mortality rate. These patients may show severe disseminated intravascular coagulation (DIC) and skin necrosis. There is very little published experience regarding the surgical treatment of this complication. The similarity between skin necrosis secondary to DIC and full thickness cutaneous burns provides the rationale for its treatment as if it was a deep burn. We report the surgical treatment of extensive skin necrosis in a patient with meningococcal sepsis and DIC. This treatment is similar to that used in full thickness burns, including excision of necrotic tissue and coverage with autografts, as well as amputation of extremities if distal coverage is not possible.

Adult↗

Dandruff as a potential source of DNA in forensic casework.

Dandruff is a clinical alteration of the skin that consists histologically of orthokeratotic clumps with minute parakeratotic foci found in inflammatory pathologies such as seborrheic dermatitis and psoriasis. Therefore, some nucleated cells should be found in dandruff and hence there is a possibility that forensically typeable DNA could be extracted from dandruff. Because of a particular case in which we were involved, a study was carried out to determine whether or not DNA could be extracted from dandruff, and if the two most widely used extraction techniques (Chelex and organic) would be applicable. Results show that sufficient quantities of DNA (more than 30 to 40 ng) can be obtained from as little as 1.0 to 1.5 mg of dandruff. Both methods yield DNA, although the organic procedure seems to yield more (72.5 ng Chelex vs. 183.3 ng organic). All the DNA samples extracted were typed correctly for the loci HUMTH01 and HUMvWA. Therefore, dandruff can be considered a potential source of DNA for forensic identification.

Clothing↗