External quality assurance programs as a tool for verifying standardization of measurement procedures: Pilot collaboration in Europe.

INTRODUCTION: Current external quality assurance schemes have been classified into six categories, according to their ability to verify the degree of standardization of the participating measurement procedures. SKML (Netherlands) is a Category 1 EQA scheme (commutable EQA materials with values assigned by reference methods), whereas SEQC (Spain) is a Category 5 scheme (replicate analyses of non-commutable materials with no values assigned by reference methods). AIM: The results obtained by a group of Spanish laboratories participating in a pilot study organized by SKML are examined, with the aim of pointing out the improvements over our current scheme that a Category 1 program could provide. METHOD: Imprecision and bias are calculated for each analyte and laboratory, and compared with quality specifications derived from biological variation. RESULTS: Of the 26 analytes studied, 9 had results comparable with those from reference methods, and 10 analytes did not have comparable results. The remaining 7 analytes measured did not have available reference method values, and in these cases, comparison with the peer group showed comparable results. The reasons for disagreement in the second group can be summarized as: use of non-standard methods (IFCC without exogenous pyridoxal phosphate for AST and ALT, Jaffé kinetic at low-normal creatinine concentrations and with eGFR); non-commutability of the reference material used to assign values to the routine calibrator (calcium, magnesium and sodium); use of reference materials without established commutability instead of reference methods for AST and GGT, and lack of a systematic effort by manufacturers to harmonize results. CONCLUSIONS: Results obtained in this work demonstrate the important role of external quality assurance programs using commutable materials with values assigned by reference methods to correctly monitor the standardization of laboratory tests with consequent minimization of risk to patients.

Anomalías de la diferenciación sexual: conceptos actuales / Abnormalities of the sexual differentiation: current concepts

Las anomalías de la diferenciación sexual (ADS) son patologías poco frecuentes (englobadas dentro de "enfermedades raras") y que, por su complejidad y escasa frecuencia, constituyen un reto y una gran responsabilidad en el equipo de profesionales encargados de su tratamiento. En los últimos años ha habido grandes cambios tanto en su nomenclatura, como en los métodos diagnósticos, así como en lo tipos de técnicas quirúrgicas, y en las edades más idóneas para llevarlas a cabo. También han cambiado los criterios para la asignación de sexo con el mínimo margen de error. En este artículo se analizan los distintos tipos de ADS, según la nueva nomenclatura, los métodos diagnósticos a emplear, las edades y técnicas quirúrgicas en uso según el sexo asignado (genitoplastia feminizante, genitoplastia masculinizante) así como el estado actual sobre el consenso de asignación de sexo. Aún hay muchos aspectos desconocidos, pero un mejor conocimiento de los mecanismos bioquímicos, genéticos y hormonales causantes de las ADS, harán posible, juntamente con los nuevos conceptos éticos y legales, conseguir un mejor enfoque y tratamiento de estos pacientes, para lograr una correcta asignación del sexo (AU)

Sexual Differentiation Alterations (SDA) are uncommon conditions (included within "rare diseases") and which, due to their complexity and limited frequency, pose a challenge and great responsibility for the professional team in charge of treating the patient. In recent years, there have been great changes in both its nomenclature and in the diagnostic methods and types of surgical treatment as well as in the best ages to conduct them. The criteria to for gender assignation has also changed with the minimum margin of error. In this article, the different types of SDA are analyzed according to the new nomenclature, diagnostic methods to be used, ages and surgical techniques in use according to the gender assigned (Feminizing genitoplasty, masculinizing genitoplasty) and the current status on the consensus of gender assignation. There are still many unknown aspects, however better knowledge of the biochemical, genetic and hormonal mechanisms causing SDA will make it possible, together with new ethical and legal concepts, to achieve a better approach and treatment of these patients, in order to achieve correct gender assignation (AU)

[Multicystic Kidney: is there any new scientific evidence to recommend nephrectomy?]. / Riñón multiquístico: existe alguna nueva evidencia científica que recomienda la nefrectomía?

With the aim to create a scientific evidence of the convenience or not of removing the Multicystic Kidney (MK), a systematic review has been done over the last 20 years, selecting those articles with determinant criterions. Our experience has been also evaluated. We have obtained an evidence table of 1082 MK, with a follow-up from 2 to 7 years. No case degenerated. The complications were: urinary tract infection (UTI) in 5% and hipertensión (HTA) in 0.7%. In our serie (68 cases): nephrectomy was done in 10 cases. 82% completely involved (66.6% before 5 years and 15.6% from 5 to 15 years of follow-up). 18% involved partially. No case degenerated. The complications were UTI (6 cases) and HTA in one. Periodical ultrasound follow-up is our recommendation for MK due to the results of our serie and from the systematic review of the literature.

Riñón multiquístico: ¿existe alguna nueva evidencia científica que recomienda la nefrectomía? / Multicystic kidney: is there any new scientific evidence to recommend nefrectomy?

Con el fin de tratar de crear evidencia científica sobre la conveniencia o no de la extirpación del riñón multiquístico (RM), se ha realizado una revisión sistemática de la bibliografía de las últimas 2 décadas, seleccionando los estudios con determinados criterios. Asimismo se analiza nuestra casuística en los últimos 20 años. Se ha obtenido una tabla de evidencia con 1.082 casos de RM, con un seguimiento entre 2 y 7 años. Ningún caso malignizó. Las complicaciones han sido infección urinaria (IU) en un 5% e hipertensión arterial (HTA) en un 0,7%. En nuestra serie (68 casos) se realizó nefrectomía en 10 casos. El 82% desaparecieron totalmente (66,6% antes de los 5 años y 15,6% entre los 5 y 15 años de seguimiento). El 18% involucionó parcialmente. No ha aparecido ningún caso de malignización, limitándose las complicaciones a IU (6) e HTA en un caso. El seguimiento ecográfico periódico en el RM continúa siendo la aproximación terapéutica más razonable según los resultados de nuestra serie y de la revisión sistemática de la literatura relacionada (AU)

With the aim to create a scientific evidence of the convenience or not of removing the Multicystic Kidney (MK), a systematic review has been done over the last 20 years, selecting those articles with determinant criterions. Our experience has been also evaluated. We have obtained an evidence table of 1082 MK, with a follow-up from 2 to 7 years. No case degenerated. The complications were: urinary tract infection(UTI) in 5% and hipertensión(HTA) in 0.7%. In our serie (68 cases): nephrectomy was done in 10 cases. 82% completely involved (66.6% before 5 years and 15.6% from 5 to 15 years of follow-up). 18% involved partially. No case degenerated. The complications were UTI (6 cases) and HTA in one. Periodical ultrasound follow-up is our recommendation for MK due to the results of our serie and from the systematic review of the literature (AU)

[Diagnosis and surgical treatment for male pseudohermaphroditism in a multidisciplinary unit of intersexual conditions]. / Diagnóstico y tratamiento quirúrgico del pseudohermafroditismo masculino en una unidad multidisciplinaria de estados intersexuales.

The birth of a child with ambiguous genitalia represents a very stressing situation for the family, and afterwards has great social and psychological repercussion for the patient itself. Until now, the sex assignation is being done according to the phenotype. Now, with the molecular diagnosis of the genes that play a role in the sexual development, the assignation must also take into account the prognosis of response to androgens. The aim of this work is to review the 40 male pseudohermaphroditism cases controlled in our hospital and the genetic molecular diagnosis done in 19 cases, thus obtaining the certainty diagnosis. In 15 patients the mutations were located in the AR gene (androgen receptor). In 2 cases the mutation affected the SRD5A2 gene (deficiency of 5a-reductase) and in the other 2 cases it affected the HSD17BIII gene (deficiency of 17-ketoreductase). If the mutations affect the AR gene they must be assigned to the feminine sex, because of the impossibility of virilisation at puberty (lack of response to androgens). If the mutations are located in the other 2 genes they can be assigned to the masculine sex, since in puberty, they will present good response to androgens and will virilize. The molecular diagnosis offers us also the possibility to establish a prenatal diagnosis and to offer genetic advice.

[Treatment of proximal hypospadias: the onlay technique]. / [Tratamiento de los hipospadias proximales: técnica de "onlay"]

UNLABELLED: In 1987 Elder and Duckett published a modification of the Duckett technique for hypospadias repair, substituting the transverse preputial island flap for the onlay island. This modification preserves the urethral plate and has no circular anastomoses, the most common cause of fistulas and stenosis. MATERIAL AND METHODS: We present our experience in 67 cases with hypospadias (60 with chordee). The meatus was in the superior third of the penis in 15 cases, in the middle third in 29, at the base of the penis in 11, and interscrotal in 12 patients. Preoperative hormonal substitution was administer in 12 patients, correction of the chordee was possible in 66 cases, the urethral plate was dissected in 18 cases, and the Nesbit procedure in 16 cases. RESULTS: A good result was obtained in 59 cases a straight penis, meatus at the tip of the penis, good calibre of the urinary stream and a satisfactory esthetic result. Our rate of complication was of 12%, five fistulas, two partial deshicences of the preputioplasty and in one case a discrete chordee. CONCLUSIONS: We believe this is an surgical technique for one stage procedure in severe cases of proximal hypospadias with chordee with a good functional and esthetic result and few complications.

[Severe epispadias: the Mitchell's technique]. / Epispadias severos: técnica de Mitchell.

UNLABELLED: Epispadias associated or not to bladder extrophy is a congenital malformation with a difficult surgical correction. Mitchell published his technique in 1996, and it's based in the complete dissection of the uretheral band, ventral peneal skin and both corporas including their proximal insertion, that in next steps will be separated in all the length. These manoeuvres permit to: 1) Correct the dorsal incurvation; 2) Locate the urethra in a ventral position; 3) Locate the meatus at the tip of the penis with a vertical orientation. MATERIAL AND METHODS: We have performed these surgical procedure in 6 patients, 4 of them were epispadias (a 23 years old patient who had there surgical procedure, with persistent incurvation), the others two were associated with bladder extrophy, 3 had hormonal treatment previous surgery, due to a hypoplastic penis. In the two patients with bladder extrophy we used a labial mucosa graft sutured to the tubularized urethral plate to relocate the meatus at the tip of the penis. RESULTS: The esthetic results were good in all cases, 2 had a fistula that was corrected surgically.

Are equally spaced specimen collections necessary to assess biological variation? Evidence from renal transplant recipients.

The established method for determining the components of biological variation (BV) requires equispaced time intervals between samplings. In a previous study, we determined BV in renal post transplantation patients, taking advantage of the samples obtained within their clinical treatment protocol (not necessarily equispaced). To confirm the validity of this practice, we sought to determine if the use of varying sampling intervals has an effect on the results obtained in such biological variation studies. The study included two phases: comparison of the results found with identical and non-identical sampling intervals and correlation between the within-subject BV and the length of the sampling interval. There were no differences in within-subject BV between the groups or correlations with sampling intervals for any of the constituents studied. We conclude that samples acquired within established clinical protocols for kidney transplant recipients can be used for estimating BV.

Effects of polyunsaturated fatty acids on rat glomerulosclerosis induced by hypercholesterolaemic diet.

Association between lipids and renal disease has been reported recently. Its pathogenic mechanisms remain unknown. The aims of this study were to establish: (1) if a cholesterol-rich diet, alone or associated with nephrectomy, produces nephropathy; and (2) if a treatment with omega-3 polyunsaturated fatty acids (PUFA) reduces glomerulosclerotic lesions. Sixty Sprague-Dawley rats were randomized in two different groups: (A) sham operated rats and (B) uninephrectomized rats. Rats in both groups were divided into three subgroups (A1-3, B1-3) according to the diet they were fed: normal chow diet, cholesterol-rich diet (4.5%) or cholesterol-rich diet supplemented with omega-3 PUFA. Twenty weeks later, serum creatinine, creatinine clearance, serum cholesterol, triglycerides, albumin, proteinuria, mesangial cell score and focal glomerulosclerosis were assessed. Results showed that a cholesterol-rich diet significantly increased serum cholesterol, proteinuria and glomerular lesions and decreased creatinine clearance, especially in nephrectomized rats. Glomerular lesions, serum cholesterol and proteinuria ameliorated when cholesterol-rich diet was supplemented with PUFA. Hypertension was noticed only in nephrectomized rats following a normal chow diet. Simple correlation analysis showed that glomerulosclerosis correlated with renal weight, blood creatinine, cholesterol and proteinuria. In spite of some significant differences in urinary prostaglandins, no correlation with glomerular lesions was found. Multiple logistic regression analysis showed that cholesterol and proteinuria were independent risk factors for induction of glomerular sclerosis. In conclusion, a diet rich in cholesterol induces glomerulosclerosis, especially if it is associated with unilateral nephrectomy. Omega-3 PUFA administration reduces serum cholesterol, proteinuria and glomerular injury.

European multicentre evaluation of the Super Aution SA-4220 urinalysis analyser.

A multicentre evaluation of the urine test strip analyser Super Aution-4220 was carried out in six laboratories. The analytical performance of the instrument with regard to imprecision, linearity, detection limit, drift, carry-over and method comparison was studied. Using the Aution stick 8 test strip the pH, glucose, protein, ketones, bilirubin, blood, urobilinogen and leukocyte esterase were analysed. Specific gravity measurements were performed by refractive index method. Within-run and between-run imprecision determined at three levels of analyte were good. No carry-over was observed. Obtained results were linear through all the described analytical range. No significant drift was detected. Method comparison with some quantitative methods was performed and showed a good correlation with most of the analytes. The study of interferences showed minor interferences by common therapeutic drugs with the measurement of some analytes. During the assessment period of about 6 months no breakdown occurred in any laboratory. The Super Aution urine analyser appeared to be a highly automated analyser of urinary test strips. The operation was simple and the maintenance required only a few minutes a day.

Potential interfering substances on Falcor-600 and Dax-48 analytical systems.

The increasing availability and use of automatic analysers in clinical chemistry have revealed a number of endogenous interferences. We evaluated the effect of bilirubin, haemolysis and lipaemia on the Falcor-600 analytical system (Menarini Diagnostics) and the Dax-48 (Bayer Diagnostic). We studied the potential endogenous interferences in the measurement of serum glucose, urea, creatinine, cholesterol, triacylglycerols, total bilirubin, total protein, aspartate aminotransferase, alanine aminotransferase and gamma-glutamyltransferase on both analysers; and albumin, direct bilirubin, uric acid, inorganic phosphorus, iron, calcium, magnesium, chloride, sodium, potassium, alkaline phosphatase, amylase, lactate dehydrogenase and creatine kinase on the Dax-48. We followed the guidelines of the Spanish Society of Clinical Biochemistry and Molecular Pathology. Bilirubin samples were prepared using bovine bilirubin, and studied in the concentration range of 20 to 400 mumol/l. For haemolysis, the pool was spiked with a diluted haemolysate of human red cells to achieve a concentration range of 10 to 120 mumol/l of haemoglobin. Lipaemia was studied using samples spiked with Intralipid, a fat emulsion, at concentrations from 1 g/l to 6 g/l (3 to 18 mumol/l of triacylglycerols).

[Colonic conduit: an alternative to the treatment of urinary incontinence]. / Conducto colónico: alternativa en el tratamiento de la incontinencia urinaria.

We report on 9 patients where on a colon conduit has been constructed. Seven of them suffered from a bladder etrophy, one had a sacral teratoma and the remaining one a vesical rhabdomyoma. The latter two had undergone total cystectomy. This technique involves creation of a conduit with isolation of 10-15 cm of a loop of sigmoid colon. One of its ends is sutured and both ureters become reimplanted with an antireflux procedure. The other end is exteriorized through the skin. Thereafter, once any reflux or uretero-colonic stenosis has been ruled out, the cutaneous stoma is detached and anastomose to the sigmoid colon. Complete technique has been used on six patients. Three of them were operated on two stages with no complications. One patient received one uretero-ureteral anastomosis. Another one had an antireflux technique together with anastomosis between the colon conduit and the sigmoid colon in a one-stage procedure. This same patient had a continent reservoir created with a portion of stomach and the colon conduit. In three cases only the first stage of this operation has been performed and the skin stoma has not been closed because of persisting faecal incontinence. Currently 6 patients are continent (2 of them remain with occasional nocturnal incontinence). The remainder have still an open stoma. Renal function and acid-base balance are normal in all of these patients. Three of them are on bicarbonate support therapy.

Effects of long-term therapy with either heparin or low-molecular-weight heparin on serum lipid levels. A prospective study.

Beside the anticoagulant and antithrombotic activity, heparin also exerts a lipolytic activity. In a prospective study on patients with venous thromboembolism and some contraindications to coumarin therapy, a low-molecular-weight heparin (Fragmin) was compared to unfractioned (UF) heparin in terms of both efficacy and safety. A secondary aim was to study the influence of both types of heparin on serum lipid levels. Sixty-six consecutive patients who were not taking concomitant treatment with lipid-lowering drugs entered the study. Patients received treatment with either UF heparin, 10,000 IU s.c., b.d., or Fragmin 5,000 IU anti-factor Xa s.c., b.d. for a period of 3 or 6 months, according to whether the initial diagnosis was deep venous thrombosis or pulmonary embolism. Each patient was followed up at 6-weekly intervals, and blood samples were obtained at discharge, and then 6 and 12 weeks after discharge. Finally, a further sample was obtained 3 months after therapy was discontinued. Total cholesterol levels increased significantly in both groups of patients: levels increased from 193 +/- 56 to 246 +/- 63 mg/dl in the UF heparin group (p < 0.001), and from 189 +/- 53 to 222 +/- 47 mg/dl in the Fragmin group (p < 0.05). The increase was mostly due to a very strong increase in HDL cholesterol levels in patients receiving UF heparin (from 46 +/- 12 to 71 +/- 23 mg/dl; p < 0.000005). Three months after discharge, HDL cholesterol levels were significantly higher in patients taking UF heparin than in patients in Fragmin (p = 0.006). By contrast, patients on Fragmin exhibited a significant increase in LDL cholesterol levels: from 112 +/- 39 to 139 +/- 37 mg/dl; p < 0.01.

[Treatment of ureterocele by endoscopic puncture]. / Tratamiento del ureterocele mediante punción endoscópica.

Ureterocele is a congenital cystic dilatation of the intravesical segment of the ureter. As a consequence, the proximal ureter and renal pelvis become dilated and that results in renal-parenchymal pathological involvement. Management of this anomaly is still controversial. Among the therapeutical options there is a place for endoscopic punction. Our experience with 11 patients undergoing this treatment modality is reported. In all these cases endoscopic punction was the initial treatment. In 7 patients this technique was all that was needed. The technique of intravesical punction is described and its results are specified.

Peritoneal transport evaluation in peritonitis: comparison between methods.

Peritoneal dialysis patients may need solute permeability transport evaluation during acute peritonitis. The aim of this study was to assess if the simplified mass transfer coefficient (MTCS) or the peritoneal equilibration test (PET) was equivalent to the complex MTC (MTCX) in solute transport evaluation during acute peritonitis in continuous ambulatory peritoneal dialysis (CAPD) patients. We studied 15 episodes of peritonitis (PTIS). Results were compared to a baseline patient study (PRE) and a control study done 30 days after diagnosis of peritonitis (POST). All peritoneal evaluation methods showed a significant increase in solute transport during acute peritonitis compared to baseline and control studies. There was an acceptable correlation between MTCX and simplified methods including the PET in the baseline and control studies. However, correlation between MTCX and simplified methods decreased during acute peritonitis. Likewise, the PET showed a better correlation with MTCX than MTCS. We conclude that the PET has an acceptable agreement with MTCX even during acute peritonitis, so the PET can be a useful tool in evaluating peritonitis-induced peritoneal permeability changes.

Evaluation of the IL-Phoenix chemistry electrolyte analyser.

This paper reports an evaluation of the IL-Phoenix Chemistry/Electrolyte Analyser; the evaluation was carried out in accordance with internationally recognized guidelines. The evaluation was performed in three steps: evaluation in routine conditions; assessment of interferences; and study of practicability. Seven constituents were studied under routine working conditions. Within-run imprecision rangedfrom 0.6% (CV) for chloride to 3.1% (CV) for glucose. Between-run imprecision ranged from 0.9% for sodium to 6.0% (CV) for urea. Sample-related carryover was not significant. The relative inaccuracy was acceptable; drift was negligible; linearity was agreed with the range showed by the supplier. Haemoglobin produced negative interferences with sodium and chloride. Turbidity interfered negatively with sodium, chloride, potassium and total calcium, andpositively with glucose. Bilirubin showed a negative interference with sodium, chloride and creatinine.

Criteria for the assessment of analyser practicability.

This article lists the theoretical criteria that need to be considered to assess the practicability of an automatic analyser. Two essential sets of criteria should be taken into account when selecting an automatic analyser: 'reliability' and 'practicability'. Practibility covers the features that provide information about the suitability of an analyser for specific working conditions.These practibility criteria are classsified in this article and include the environment; work organization; versatility and flexibility; safely controls; staff training; maintenance and operational costs.

Mass transfer coefficient: comparison between methods.

The mass transfer area coefficient (MTC) is the best parameter for solute transport evaluation in continuous ambulatory peritoneal dialysis (CAPD) patients. We compared three simplified MTC methods (calculated according Garred, Krediet, or Lindholm) and the peritoneal equilibration test (PET) (Twardowski) to complex MTC (MTCX) (Randerson and Farrell) for urea and creatinine, by means of 29 tests performed in 24 stable CAPD patients. There were no significant differences (paired t-test) between MTCX and each of the simplified MTC, except for creatinine MTC calculated by Krediet's method, which was significantly different (MTCX: 9.36 +/- 4.32, K-MTC: 10.48 +/- 4.55, p < 0.05). Likewise, there was an acceptable correlation between complex MTC and each of the simplified methods including the PET. However, a more detailed study of the MTC's categorizations shows poor agreement with complex MTC categorization. Better results are obtained by PET categorization, which reaches good likelihood ratios either for positive or negative events. We conclude that simplified MTC or the dialysate/plasma ratio at 240 minutes for urea and creatinine has an acceptable correlation with complex MTC and can be useful in clinical practice. There is poor agreement between solute transport categorizations of simplified MTC and complex MTC. There is a better coincidence between the PET (D/P at 240 minutes) and complex MTC categorizations.