[Toxic epidermal necrolysis. Therapeutic trends].
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Adrenal Cortex Hormones↗
Biomedical subjects
J A Lorente
Publications and source records attributed to J A Lorente.
Pituitary-thyroid function in patients with septic shock and its relation with outcome.
OBJECTIVE: To study the time course of thyroid function abnormalities and their relation to outcome in patients with septic shock. DESIGN: Prospective study in a cohort of consecutive patients. SETTING: Intensive Care Unit in a University Hospital. PATIENTS AND METHODS: We studied 27 patients (mean age 50 +/- 19 years, Apache II score 18.4 +/- 5.2, 15 survivors) diagnosed of septic shock. Total T4 (T4) and total T3 (T3) (RIA) were determined on days 1 and 5 after admission. We also measured TSH (ultrasensitive RIA) at 08.00, 20.00 and 01.00 hours (on days 1 and 5), and the TSH response to TRH (400 microg intravenous) on days 2 and 6. Data are mean +/- SD. RESULTS: Whereas low thyroid hormones concentrations were present on day 1 in all patients, only survivors presented a significant increase in T3 and T4 on day 5. Basal TSH levels and the area under the curve of the TSH response to TRH on day 2 were significantly higher in survivors than in non survivors (0.89 +/- 0.63 vs. 0.34 +/- 0.42 microIU/ml, and 229 + 157 vs. 101 + 101). The normal nocturnal (01.00 hr) surge of TSH (the difference between TSH concentrations at 8 am and at 1 am) was abolished in both survivors and non survivors on day 1 but it was recovered on day 5 only in survivors. CONCLUSIONS: Our data indicate that patients with septic shock present an altered hypothalamic-pituitary-thyroid axis, and that survivors thyroid function differs from that of non survivors shortly after diagnosis. Survivors are characterised by a greater TSH response to TRH, indicating a less deranged hypothalamic-pituitary-thyroid axis. Thyroid function improves in survivors, but not in non survivors, during the course of their illness.
Adult↗
Measurement of free PSA in the diagnosis and staging of prostate cancer.
The purpose of this study was to analyze the role of total prostate-specific-antigen (PSA) and free-PSA levels in the diagnosis and clinical staging of prostate cancer. We determined total-PSA serum concentration and free-PSA percentage in 352 patients, 234 with benign prostatic hyperplasia (BPH) and 118 with prostate cancer. Clinical stage of patients with prostate cancer was T1 N0 M0 in 17, T2 N0 M0 in 27, T3-4 N0 M0 in 34 and T1-4 N0-3 M0-1 in 40. Median total-PSA serum concentration was 3.1 ng/ml in patients with BPH and 26.9 ng/ml in patients with prostate cancer, p < 0.0001. Median free-PSA level was 16.7% in patients with BPH and 8.1% in patients with prostate cancer, p < 0.0001. A cutpoint of 4.0 ng/ml detected 96.6% of the prostate cancer, but the percent rate of negative biopsies was 42.1%. For a free-PSA level of 25% in patients with total PSA greater than 4.0 ng/ml, the sensitivity was 97.4%, and the decrease in negative biopsies was 21%. Median total-PSA serum concentration in patients with prostate cancer according to clinical stage was 8.9 ng/ml for T1 N0 M0, 12.9 ng/ml for T2 N0 M0, 29.9 ng/ml for T3-4 N0 M0 and 317 ng/ml for T1-4 N1-3 M0-1, p < 0.001. Median free-PSA levels were 10.1%, 8.1%, 8.4% and 6.1% respectively, p > 0.05. According to the Gleason score, median total-PSA serum concentration was 10.6 ng/ml in patients between 2 and 4, 22.3 ng/ml between 5 and 7 and 77.0 ng/ml between 8 and 10, p < 0.05. Free PSA levels were 7.7%, 8.7% and 6.6% respectively, p > 0.05. Determination of percentage of free PSA appears to be a helpful method for enhancing the specificity of total PSA. A cutpoint of 25% could detect more than 95% of prostate cancers and avoid 21% of negative biopsies in patients with total PSA above 4.0 ng/ml. However, this parameter does not provide additional information about the clinical staging of prostate cancer.
Biopsy↗
Spanish population data on seven loci: D1S80, D17S5, HUMTH01, HUMVWA, ACTBP2, D21S11 and HLA-DQA1.
Blood samples from 120 Spanish Caucasian individuals were amplified and typed by electrophoresis at six loci, and by reverse dot-blot hybridization at one locus. Results demonstrate the assumption of independence within and between the seven loci analyzed. Therefore, a Spanish population database has been established and statistical analysis shows that a high degree of discrimination can be obtained when all seven (or fewer) loci are used to characterize forensic biological evidence.
DNA↗
A review of the collaborative exercises on DNA typing of the Spanish and Portuguese ISFH Working Group. International Society for Forensic Haemogenetics.
Since 1992 the Spanish and Portuguese Working Group (GEP) of the International Society for Forensic Haemogenetics (ISFH) has been organizing collaborative exercises on DNA profiling with the aim of making progress on standardization and discussing technical and statistical problems in DNA analysis. A total of four exercises (GEP-92 to GEP-95) have been carried out until now. A consequence of these exercises was the creation of a quality control programme in Spain and Portugal in 1995 which was carried out simultaneously with the GEP-95 exercise. The number of participating laboratories increased from 10 in the first exercise (GEP-92) to 19 in the last exercise (GEP-95). Despite this increasing number of participating laboratories, results remained satisfactory. In the last exercises, all the laboratories used PCR-based DNA polymorphisms with an increasing number of markers obtaining good results. SLPs were used by only 30% of laboratories in the last two exercises but the results indicated a good level of expertise in most of these laboratories. The reasons for these successful results are the common use of the EDNAP protocol for SLP analysis and commercially available kits or common sequenced allelic ladders for PCR-based DNA polymorphisms.
Blood Stains↗
Indisputable double paternity in dizygous twins.
OBJECTIVE: To report a case of heteropaternal superfecundation. DESIGN: Case report. SETTING: University paternity laboratory. PATIENT(S): Father, mother, and a set of twins. INTERVENTION(S): Blood typing conventional markers, as well as polymerase chain reaction loci and restriction fragment length polymorphism loci of DNA. MAIN OUTCOME MEASURE(S): Heteropaternal superfecundation was demonstrated after paternity investigation. RESULT(S): The probability of paternity for twin 1 was 99.9999998%, whereas that for twin 2 was excluded on the basis of the following tests: Fy, Pi, human leukocyte antigen (HLA)-DQA1, D1S80, D17S5, HBGG, D5S110, D2S44, and D10S28. CONCLUSION(S): Dizygous twins can have different biologic fathers, as demonstrated in this case. According to published data, the frequency of twins with different fathers is probably underestimated, at least in small selected populations such as those of paternity suits.
Blood Grouping and Crossmatching↗
An improved method to recover saliva from human skin: the double swab technique.
Human bite mark evidence is often found in violent crimes. Due to the difficulties of physically comparing an injury site on elastic and curved skin surfaces to the teeth of a suspect, the authors have considered using salivary DNA evidence to identify the bite perpetrator. Several techniques were evaluated to determine the best method of recovering saliva from human skin before extracting genomic DNA from the collection substrate. A classical stain recovery technique using a wet cotton swab was tested against one utilizing a wet filter paper. Additionally, a new method, referred to as the double swab technique, using a wet cotton swab followed by a dry cotton swab was also evaluated. After recovering a dried saliva stain, DNA was extracted using the modified Chelex method, quantified using the slot-blot procedure, and amplified at three polymorphic loci. The double swab technique showed the highest percentage recovery of saliva from human skin among the three methods studied. This technique is suggested as an improvement over the classical single wet cotton swab technique.
Bites and Stings↗
PCR-based DNA typing of saliva stains recovered from human skin.
Human bites in cases of homicide, sexual assault, and abuse are often distorted due to the elasticity and curvature of the skin. Physical comparison of a bite mark to a suspect's teeth is sometimes difficult. Saliva, which is usually deposited during biting, can be collected and analyzed to identify the perpetrator. Using simulated bite mark situations in two experimental series, three samples of 40 microL of whole saliva were deposited on the skin of 27 cadavers (at 33 sites) and three samples of 100 microL of whole saliva were deposited on the skin of 5 cadavers (at 12 sites). Saliva was collected using the double swab technique at t = 5 min, t = 24 h, and t = 48 h. DNA was extracted using the modified Chelex method and submitted to PCR-based typing at two short tandem repeat loci. Results indicate that the concentration of DNA in saliva recovered from skin varies as a function of time since deposition. There is a significant decrease in concentration in the first 24 h but the concentration remains stable from 24 to 48 h. The success of PCR amplification is independent of the time since deposition or the concentration of DNA in the saliva sample. Contamination from the DNA of the cadaver was not found in any of the cases studied.
Bites, Human↗
Comparison of percent free prostate specific antigen and prostate specific antigen density as methods to enhance prostate specific antigen specificity in early prostate cancer detection in men with normal rectal examination and prostate specific antigen between 4.1 and 10 ng./ml.
PURPOSE: We analyzed the behavior of prostate specific antigen (PSA) density and percent free PSA to enhance the specificity of PSA in the early diagnosis of prostate cancer in men with normal digital rectal examination and PSA serum level between 4.1 and 10 ng./ml. MATERIALS AND METHODS: PSA serum level, PSA density and percent free PSA were analyzed in 74 men with normal digital rectal examination and PSA serum level between 4.1 and 10 ng./ml. All men underwent systematic prostate biopsy, and the diagnosis was benign prostate hyperplasia in 52 and prostate cancer in 22. Furthermore, we determined the decrease in unnecessary biopsies and the cancer detection rate using 0.10 versus 0.15 as cut points for PSA density, and 20 versus 25 as cut points for percent free PSA. RESULTS: In patients with benign prostatic hyperplasia and prostate cancer, respectively, the median PSA level was 6.7 and 7.0 ng./ml. (p > 0.05), median prostate volume was 50 and 37 cc (p < 0.04), median PSA density was 0.14 and 0.19 (p < 0.007) and median percent free PSA was 18.9 and 10.1 (p < 0.005). Using PSA density cut points of 0.15 and 0.10, the decrease in negative biopsies was 53.8 and 36.5% with a sensitivity of 86.4 and 90.9%, respectively. However, using percent free PSA cut points of 20 and 25, the decrease in negative biopsies was 36.5 and 26.9% with a sensitivity of 77.3 and 95.5%, respectively. CONCLUSIONS: Although both methods could minimize unnecessary biopsies in men with normal digital rectal examination and PSA serum level between 4.1 and 10 ng./ml., the percent free PSA was more cost-effective since transrectal ultrasound was not required. In this small series of symptomatic patients a percent free PSA cut point of 25 could detect at least 95% of prostate cancers and decrease 26.9% of negative biopsies.
Aged↗
Sequential multiplex amplification: utility in forensic casework with minimal amounts of DNA and partially degraded samples.
Since its introduction, PCR has become a widely-used, routine technique in forensic laboratories. A number of PCR protocols that were developed originally are now being replaced by more powerful approaches, particularly those based on multiplex amplification of short tandem repeat (STR) loci. One alternative from of multiplex PCR amplification, called Sequential Multiplex Amplification (SMA), was designed to amplify a single locus and then recover and reuse the remaining genomic DNA as a template for subsequent PCR. The SMA process could be repeated several times. SMA has proven to be useful in typing genomic DNA contained in stored PCR samples and analyzing samples of limited quality and/or quantity for multiple loci. The efficacy of the use of SMA for actual typing of casework samples permitted typing for a second locus 98.11% of the samples considered; 70.75% were typeable for a third locus, and 16.98% for a fourth locus.
Blood Stains↗
[Septic shock and nitric oxide].
Refractory hypotension is the main cause of death of patients with septic shock. It has been shown that an excessive release of NO is responsible for the sepsis-induced hypotension and vascular hyporeactivity. Nitric oxide is produced under normal conditions by a constitutive enzyme present, among other cell types, in the endothelial cell, and is necessary for maintenance of normal organ perfusion. Under inflammatory or septic conditions, a new enzyme is expressed in phagocytic cells and vascular smooth muscle cells, giving rise to an uncontrolled NO production that is associated with cytotoxic effects and vasodilatation. Randomized clinical trials have shown that the administration of inhibitors of NO synthesis to patients with septic shock is associated with a greater incidence of shock resolution, without significant adverse effects. The recent discovery of the different biological functions of NO, both under normal and inflammatory conditions, has allowed the development of new concepts about the pathophysiology of septic shock, and has provided the bases to design novel therapeutic strategies for the treatment of septic shock, based on the inhibition of NO synthesis.
Arginine↗
[Influence of renal and hepatic function in the serum concentration of prostate specific antigen].
The influence of renal and hepatic functioning on serum levels of prostate specific antigen has been studied by examining its behaviour in a control group (CG) of 178 healthy male, a group of 48 patients with end-stage renal failure (ESRF) 22 of which had pre- and post-dialysis PSA measurements and a group of 48 patients with chronic liver failure (CLF). Mean PSA level in CHF, 0.64 ng/ml, was lower (p < 0.001) than the level seen either in CG, 1.37 ng/ml, and ESRF, 1.33 ng/ml, the last two exhibiting no statistical difference. Also, no significant differences were seen between pre- and post-dialysis PSA levels, 1.52 and 1.33 ng/ml respectively. The authors conclude that renal functioning has little relevance in the regulation of PSA serum levels and that, in spite of levels being lower in liver failure, this does not seem to be meaningful in the clinical practice.
Adult↗
Increasing DNA extraction yield from saliva stains with a modified Chelex method.
Recovery, preservation and analysis of body fluid stains is an important aspect of forensic science. PCR-based typing of DNA extracted from recovered stains is often a crucial method to identify a perpetrator or exclude an innocent suspect. This paper reports an improved method of extracting genomic DNA from saliva stains deposited on human skin in simulated bite mark situations. Results of organic (phenol-chloroform) extraction and Chelex extraction were compared to a modified Chelex method developed by the authors. Modifications include pre-extraction preparation with proteinase K and incubations at 56 degrees C and 100 degrees C plus microconcentration of the solution. Quantification results using the classical Chelex extraction method showed that 31.9 +/- 4.22% of the deposited DNA was recovered, but using the modified Chelex extraction method DNA recovery was increased to 47.7 +/- 6.90%. The quantity and quality of extracted DNA was shown to be adequate for PCR-based typing at two STR loci.
Bites and Stings↗
Prostate carcinoma staging. Clinical utility of bone alkaline phosphatase in addition to prostate specific antigen.
BACKGROUND: Biochemical markers of bone disease have been of interest as part of the investigation of prostate carcinoma and the monitoring of skeletal involvement. Bone isoenzyme of the alkaline phosphatase (BAP) is an indicator of the metabolism of the osteoblasts. An immunoradioanalyses with two monoclonal antibodies in sandwich was developed, allowing an accurate measurement of BAP concentration. The goal of the current study was to compare the clinical performance of BAP and prostate specific antigen (PSA) in patients with untreated prostate carcinoma and to determine whether or not BAP can provide valuable additional information to PSA regarding the degree of skeletal extension in patients with prostate carcinoma. METHODS: BAP and PSA serum concentrations were determined in 140 newly diagnosed prostate carcinoma patients (72 M0 and 68 M1-4). The efficiency of both markers in the prediction of positive bone scans was studied as well as the relationship observed between the concentrations of the two markers and the degree of skeletal involvement. To investigate the potential utility of BAP and PSA in eliminating the need for a bone scan, the negative predictive values for different cutoff points for both markers were calculated. RESULTS: BAP was more efficient than PSA in the prediction of positive bone scans and its level was significantly related to the magnitude of skeletal involvement whereas PSA was only able to distinguish between M0 and M1-4 groups of patients. The highest predictive value for a bone scan result was found for BAP cutoff values between 20 and 30 ng/mL, leading to negative and positive predictive values of 92.6% and 98.2%, respectively. The combination of BAP and PSA both set at a 20 ng/ mL cutoff value yielded a negative predictive value of 100% and the combination of BAP and PSA at 30 ng/mL and 20 ng/mL cutoff values, respectively, increased the positive predictive value to 98.5%. CONCLUSIONS: This study suggests that BAP could be a complementary marker to PSA in the diagnosis of bone disease in patients with prostate carcinoma. Its clinical utility could result in important cost saving implications, eliminating bone scan when PSA ranges from 10 to 20 ng/mL because the predictive negative value of PSA < 20 ng/mL and BAP < 20 ng/mL is 100% in this series. In addition, it could provide useful clinical information regarding the degree of skeletal involvement.
Adult↗
Effects of nitric oxide synthase inhibition on the cardiovascular response to low output shock.
OBJECTIVE: To study the role of nitric oxide in the cardiovascular response to a model of a low output syndrome. DESIGN: Prospective animal study. SETTING: Animal research laboratory. SUBJECTS: Sheep anesthetized with pentobarbital, mechanically ventilated, and monitored with pulmonary arterial and peripheral arterial catheters. INTERVENTIONS: A low output state was induced by inflating a balloon-tip catheter placed in the right atrium. Cardiac index was maintained at 1 L/min/m2 throughout the experiment in three groups of sheep: a) control (n=6) b)LNNA group (pretreated with the nitric oxide synthase inhibitor N omega-nitro-L-arginine [LNNA, 100 mg/kg, iv bolus, n=6); and c) dexamethasone group (pretreated with dexamethasone (6 mg/kg, intravenous bolus, n=6). Dexamethasone is an inhibitor of the induction of nitric oxide synthase. LNNA or dexamethasone were administered 15 mins before inducing the low output state. MEASUREMENTS AND MAIN RESULTS: Hemodynamic and oxygen transport variables, and plasma lactate and pyruvate concentrations, were measured at baseline and during the next 3 hrs. For a comparable decrease in cardiac index and oxygen delivery in all groups, the LNNA group had less hypotension and a more marked increase in systemic vascular resistance as compared with the control group. Oxygen consumption and oxygen extraction were higher in the LNNA group as compared with the control group at 30 and 60 mins. Plasma lactate concentration increased significantly less in the LNNA group than in the control and the dexamethasone groups during the observation period. CONCLUSIONS: Inhibition of nitric oxide synthesis during a severe low output state in sheep is associated with a better hemodynamic response, as evidenced by a greater vasoconstriction, and signs of less marked tissue hypoxia. It is likely that inhibition of nitric oxide synthesis in this model leads to an imbalance between the tonic relaxing action of nitric oxide and the influences of vasoconstrictor agents.
Analysis of Variance↗
Clinical efficacy of bone alkaline phosphatase and prostate specific antigen in the diagnosis of bone metastasis in prostate cancer.
PURPOSE: We investigated the usefulness of bone alkaline phosphatase isoenzyme and prostate specific antigen (PSA) determined by radioimmunoassay to predict bone scan evidence of metastasis in newly diagnosed untreated and treated prostate cancer. MATERIALS AND METHODS: We analyzed bone alkaline enzyme concentrations in 350 men, including 150 controls, 100 with benign prostatic hyperplasia and 100 with prostate cancer (52 with stages T1 to 4, M0 and 48 with stages T1 to 4, M1 to 4). We also analyzed bone alkaline phosphatase enzyme concentrations in 61 stages T1 to 4, M0 prostate cancer cases during followup after radical prostatectomy or hormonal therapy, and 17 had clinical progression (9 with local, 5 with lymph node and 3 with bone metastases). Simultaneously, we analyzed PSA concentrations. RESULTS: Average bone alkaline phosphatase enzyme levels were 12, 11.1 and 10.0 ng./ml. in the control, benign prostatic hyperplasia and stage M0 prostate cancer groups, respectively (p not significant), and 83.2 ng./ml. in patients with stage M1 to 4 disease (p<0.001). Considering that to diagnose bone metastasis the cutoff for bone alkaline phosphatase enzyme and PSA is 30 ng./ml. and 100 ng./ml., respectively, clinical effectiveness was 93.7% and 81.8%, respectively. Finally, measurement of both substances at the same time increased clinical effectiveness to 97.9%. During followup a bone alkaline phosphatase enzyme level that becomes greater than 30 ng./ml. (0% in the local and lymphatic progression groups, and 100% in the bone metastasis group) indicates the need to perform a bone scan. CONCLUSIONS: We recommend the clinical use of bone alkaline phosphatase enzyme determined by radioimmunoassay and PSA measurement for the diagnosis of bone metastases and progression of prostate cancer because of the good sensitivity and specificity.
Aged↗
[Cardiorespiratory arrest as the first manifestation of hypothyroidism].
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Adult↗
[Final results of complete hormone blockade versus monotherapy in prostatic metastatic cancer. PSA implications].
Of 102 patients with metastatic prostate cancer, 52 were treated with orchidectomy and 50 with CHB; 22 of these received a LHRH analog + Flutamide and 28 orchidectomy + Flutamide. No differences were seen in either arm in terms of age (69.9 vs 70.2 years) or initial PSA (493.3 vs 486.5 ng/ml) variables. After three months treatment, CHB achieved a decrease of PSA higher than monotherapy (52.9 vs 34.5 ng/ml) p<0.01 as well as minimum PSA level during follow-up (41.2 vs 17.5 ng/ml) (p<0.001). Initial clinical response rates were higher in the group treated with complete blockade (42.3% vs 52%) (p=n.s.). Overall, no significant differences were seen between the actuarial curves of biological progression, clinical progression and survival, with expected mean values of 13 vs 12, 14 vs 15 and 34 vs 28 months, respectively. However, when survival was considered as a function of bone disease dissemination, a greater survival rate was seen in patients with minimal M1 disease (p<0.05), and there were no differences between the M2 and M3 arms.
Actuarial Analysis↗