Sequencing of the new HLA-B*44:150 allele suggests recombination between B*44:02:01:01 and B*07:02:01 alleles.

B*44:150 was identical to B*44:02:01:01 except at the 3'-end region of exon 3, where a B*07-specific sequence was identified.

Report From the First and Second Spanish Killer Immunoglobulin-Like Receptor Genotyping Workshops: External Quality Control for Natural Killer Alloreactive Donor Selection in Haploidentical Stem Cell Transplantation.

An important factor affecting the success in the setting of related haploidentical hematopoietic stem cell transplantation (HSCT) is the graft-versus-leukemia effect mediated by natural killer (NK) cells when the donor displays NK alloreactivity versus the recipient. NK cell function is regulated by killer immunoglobulin-like receptors (KIR) and it has been described that donor KIR genotype influences transplantation outcome. This has led to a requirement of laboratories to have a quality assurance program for validation and control of their KIR genotyping methods. The goal of the 1st and 2nd Spanish KIR Genotyping Workshops was to provide an external proficiency testing program in KIR genotyping for Spanish immunology and transplant laboratories. These workshops were conducted during the years 2014-2016 and consisted of 17 participating laboratories typing a set of 20 samples. The presence/absence of 16 mandatory KIR loci (2DL1, 2DL2, 2DL3, 2DL4, 2DL5, 2DS1, 2DS2, 2DS3, 2DS4, 2DS5, 2DP1, 3DL1, 3DL2, 3DL3, 3DS1, and 3DP1) was evaluated per sample. Methods for KIR genotyping included polymerase chain reaction with the use of sequence-specific primers and sequence-specific oligoprobes. Consensus typing was reached in all samples, and the performance of laboratories in external proficiency testing was satisfactory in all cases. The polymorphism detected in the small sample studied in both workshops is indicative of an ample variety of KIR gene profiles in the Spanish population.

[Serological and genetic markers in the diagnosis and follow-up of coeliac disease]. / Marcadores serológicos y genéticos en el diagnóstico y seguimiento de la enfermedad celíaca.

INTRODUCTION: Understanding of celiac disease has changed with the advent of serological markers (antigliadin IgA, anti-endomysial IgA and anti-transglutaminase IgA antibodies) and with the identification of major susceptibility genes (HLA-DQA1*05-DQB1*02). Reports of the efficacy of these diagnostic tests have varied, depending on the methodology used and the population investigated. OBJECTIVES: To determine the clinical utility of genetic and serological markers in the diagnosis of celiac disease, their relationship with histological lesions and their changes during treatment, in order to establish an optimal diagnostic algorithm in our environment. PATIENTS AND METHODS: We performed a retrospective study of 590 patients from the health area of Badajoz referred to the Immunology Laboratory for screening or follow-up of celiac disease. The results of intestinal histology, serological markers (antigliadin IgA, anti-endomysial IgA and anti-transglutaminase IgA antibodies), and genomic typing (HLA-DQA1*05-DQB1*02) were analyzed. RESULTS: The sensitivity and specificity of serological tests were greater than 90 %, with a negative predictive value of 98-100 %. HLA-DQA1*05-DQB1*02 was detected in 97 % of celiac patients, with a very high negative predictive value (99 %). On biopsy, 95 % of the patients with some grade of intestinal lesion were positive for antigliadin and/or anti-endomysial antibodies. CONCLUSION: To avoid missed diagnoses, the diagnostic algorithm of celiac disease should include at least two serological markers (antigliadin antibodies and anti-endomysial and/or anti-transglutaminase antibodies) and IgA quantification. Genomic typing should be carried out if one or more markers are positive or if the subject belongs to any of the risk groups. The physician should decide on the advisability of intestinal biopsy on the basis of the patient's clinical and immunological history.

Relationship of tumoral hyaluronic acid and cathepsin D contents with histological type of gastric carcinoma.

The aim of this work was to evaluate the cytosolic contents of hyaluronic acid (HA) and cathepsin D (CatD) in gastric carcinomas and their possible relationships with the clinicopathological parameters of the tumors. Our study demonstrated a wide variability in the cytosolic levels of HA (mean +/- SEM: 3748 +/- 411 ng/mg protein) and cathepsin D (52 +/- 4 pmol/mg protein) in the tumors of 78 gastric cancer patients. In addition, the tumoral contents of HA and CatD were significantly higher (p<0.005) in diffuse type (HA: 6027 +/- 1099 ng/mg protein; CatD: 75 +/- 13 pmol/mg protein) than in intestinal type (HA: 2735 +/- 242 ng/mg protein; CatD: 42 +/- 3 pmol/mg protein) carcinomas. These data suggest that both markers may contribute to the biological characterization of gastric carcinomas.

Phagocytic activity of polymorphonuclear leukocytes on Escherichia coli previously exposed to metronidazole.

A study was made of the action of different concentrations of metronidazole of the viability of Escherichia coli under aerobic and anaerobic conditions. The viability of E. coli was reduced by 60 to 99% after 24 hours of anaerobic incubation, according to the concentration of metronidazole tested. In addition, there were significant morphological changes in the bacteria. Exposure of antibiotic-induced filaments of E. coli LP 136 to phagocytosis caused the cfu/ml value to drop by 60% after 120 minutes. Under identical conditions, using the mutant strain E. coli RYC 819, which did not become filamented by metronidazole although it did present similar ultrastructural changes, this reduction reached 83%. These results may explain the therapeutic success of metronidazole in polymicrobial infections.

[Sturge-Weber syndrome with atypical calcifications]. / Síndrome de Sturge-Weber con calcificaciones atípicas.

INTRODUCTION: The syndrome, or disease, or Sturge Weber (SSW) is a neuro-ectodermic disorder of unknown incidence, sporadic presentation and specific sex incidence. It is characterized by the presence of a flat, facial angioma which affects at least the first branch of the trigeminal nerve, association with ipsilateral leptomeningeal vascular anomalies, one or more symptoms (epilepsy, hemiparesia, hemiplegia or mental retardation) and ipsilateral vascular lesions of the choroid which lead to glaucoma. As a consequence of lepto-meningeal involvement, homolateral cerebral hemi-atrophy develops together with cortico-subcortical calcifications with a characteristic "railway line" appearance. CLINICAL CASE: We present the case of a six month old girl with a flat port wine angioma on the left half of her face, including three branches of the trigeminal nerve and the left half of her body. She had partial motor crises of the right leg. On the cranial CT there were left periventricular calcifications and calcifications of the choroid plexus. Gadolinium-MR showed signs of left cerebral hemi-atrophy, which was confirmed on the cerebral SPECT (left temporal hypoperfusion). CONCLUSION: This case is interesting on account of the presence of atypical calcifications, both with regard to the sites and age of presentation. We emphasize the need for cranial CT to rule out the presence of calcifications, (as in this case) not seen on Xray of the skull or on MR. We favour the use of cerebral SPECT as a complementary diagnostic technique.

[Intercritical SPECT in drug-resistant partial epilepsy with normal MRI: a study of 33 cases]. / SPECT intercrítica en la epilepsia focal farmacorresistente con RM normal: estudio de 33 casos.

We made a prospective study of the intercritical changes in cerebral perfusion using SPECT with 99mTc-HMPAO in 33 adult patients with focal epilepsy which was resistant to polypharmacy and showed normal MR, to evaluate the relationship between these changes and the clinico-electrical focus (FCE) and the clinical features of epilepsy. All SPECT studies (100%) showed one or more areas of hypoperfusion. There was good topographical relationship between the perfusion defects and FCE which coincided exactly in 15 patients (45.4%); was acceptable with FCE identification but with associated defects in 12 (36.4%) and poor, bearing no relation to each other in 6 (18.2%). There was no correlation between a good, acceptable or poor relationship of SPECT-FCE and the age of the patient, time-course of the illness, number of crises, number of drugs or type of treatment given. There were more cases showing poor relationship amongst the pure temporal lobe foci (p < 0.05), but when these were considered together with the fronto-temporal cases, no difference was seen when compared with the extra-temporal cases. There was a tendency to greater secondary generalization of the crises in the group showing a good relationship. There were more cases of a clinical history of previous CNS diffuse lesions (anoxia, trauma or meningitis) amongst those with a poor relationship (83%) but not amongst those with a good relationship (20%, p < 0.05), or an acceptable relationship (25%, p < 0.05). This would seem to suggest that the anomalies found were more a result of the cause of the epilepsy than of the repetition of crises. SPECT should be included in the diagnostic algorithms of focal epilepsy with normal.

[Valoration of the epidermal growth factor receptor (EGFR) in benign breast disease and its relation with expression in malignant tumors classified by hormonal dependence]. / Valoración del receptor del factor de crecimiento epidérmico (EGFR) en patología benigna de la mama y su relación con la expresión en tumores malignos clasificados en función de su dependencia hormonal.

The aim of this work is studying the behaviour of EGFR in benign breast pathologies and correlating it to its expression in CDI with hormonal dependency or independency using a radioligand technique. The EGFR expression was higher in FAD rather than in MFQ (mean +/- S.D.: 13.7 +/- 13.5; range: 1.0-55.3; median: 10.0 fmol/mg prot vs mean +/- S.D.: 4.0 +/- 3.5; range:1.0-11.4; median: 2.2 fmol/mg prot), with a result of a positive correlation in the first ones with RP (r = 0.4557) but not with RE. FAD present similar EGFR concentrations to those in CDI-hormonal independents (mean +/- S.D.: 10.7 +/- 12.6; range: 1.0-60.2; median: 6.75 fmol/mg prot), even though the way they are correlated with the content in RP leads us to the conclusion that they are both involved in the genesis and controled development of themselves. On the other hand, MFQ have got similar contents in EGFR to those of CDI hormono-dependents (mean +/- S.D.: 6.98 +/- 15.72; range: 1.0-118; median: 2.55 fmol/mg prot); this fact proves that the development of this pathology does not only depend on the growth factors but also on the hormonal environment which influences it.

[Analysis of the cytosolic content of the pS2 protein in breast cancer]. / Análisis del contenido citosólico de la proteína pS2 en el cáncer de mama.

OBJECTIVE: To analyze pS2 cytosolic levels in breast carcinomas and their correlation with different clinical characteristics of the patients and their tumours. MATERIAL AND METHODS: Cytosolic pS2 levels were measured by radioimmunometric assay in tumours from 168 breast cancer patients. RESULTS: The pS2 values ranged from 0 to 251 ng/mg protein (mean SD: 21.8 38.1; median: 7.9 ng/mg protein). These protein levels were significantly (p < 0.05) higher in premenopausal patients (27.6 45.2) than in postmenopausal patients (19.5 33.8). Intratumour pS2 levels were also significantly (p < 0.05) correlated with histologic grade of the tumours, and were higher in well diferentiated tumours (grade I: 28.8 42.8) than in moderately differentiated tumours (grade II: 19.7 35.6) and than in poorly differentiated tumours (grade III: 18.9 37.3). Similarly, significant differences in pS2 content were found between positive estrogen receptor (ER) tumours and ER-negative tumours (29.1 46.5 vs 11.3 15.9, respectively; p<0.0001), as well as between positive progesterone receptor (PR) tumours and PR-negative tumours (29.1 49.8 vs 15.3 21.5, respectively; p < 0.05). CONCLUSIONS: The results suggest that pS2 may be a useful prognostic marker in breast cancer, and may also be useful to identify patients who are likely to benefit from hormone therapy.

[Preoperative serum levels of the carcinoembryonic antigen (CEA) and prognosis in colorectal cancer]. / Niveles séricos preoperatorios del CEA y pronóstico en el cáncer colorrectal.

OBJECTIVE: To analyze the prognostic value of the preoperative serum levels of the carcinoembryonic antigen (CEA) in primary colorectal carcinoma. MATERIAL AND METHODS: Preoperative serum levels of CEA were analyzed in 275 colorectal cancer patients, who were followed up for a minimum of 5 years, or until death. RESULTS: The percentage of positivities for the preoperative serum levels of CEA (> 6 ng/ml) was positively and significantly associated with the tumoral stage (A: 10,5%; B: 38,8%; C: 32,2%; y D: 72%; p < 0,0001). In addition, the elevated serum values of the antigen were significantly associated, in the univariate analysis, with short survival in the overall group of patients (p < 0,0001). However, the multivariate analysis only showed an independent prognosis value of the CEA in the subgroup of patients with stage C tumors. CONCLUSIONS: Preoperative serum levels of CEA may be useful to predict tumoral extension, and also for the prognosis regarding stage C colorectal cancer patients.

Clinical relevance of incidental finding of focal uptakes in the colon during 18F-FDG PET/CT studies in oncology patients without known colorectal carcinoma and evaluation of the impact on management.

AIMS: To assess the significance and the impact of focal FDG uptake in the colon in oncology patients without known colorectal carcinoma. MATERIALS AND METHODS: A retrospective study was undertaken on 2,220 (18)F-FDG PET/CT studies carried out consecutively in the Nuclear Medicine Department in our hospital from 2 December 2008 to 31 May 2010. Inclusion criteria were patients with abnormal (18)F-FDG uptake in colorectal area that could not be explained (or not previously known) by their clinical histories. Patients previously diagnosed with colorectal carcinoma were excluded. A total of 86 patients (57 male, average age 63.4, range 46-85) were finally included. Colonoscopy with biopsy was established as a reference test. The impact of these findings on the diagnostic-therapeutic management in these patients was evaluated. RESULTS: A colonoscopy was performed in 54 of the 86 patients, this examination not having been done up-to-date in the remaining 32 patients. Biopsy was obtained in 43 lesions of the 54 patient in whom a colonoscopy was performed. Colon disease was detected in 49 of these 54 patients, obtaining 54 FDG incidental foci which corresponded to 10 previously unsuspected primary colorectal carcinoma, 3 metastases, 27 adenomatous polyps with different degrees of dysplasia and 14 inflammatory processes. In the remaining 5 patients, the colonoscopy was normal. PET/CT modified the diagnostic and treatment management in most of the patients (49/54, that is 91%). CONCLUSIONS: These results confirm the need to determine the cause of abnormal (18)F-FDG colorectal uptakes in the PET/CT studies by using colonoscopy and biopsy. This approach allows for the detection and early treatment of malignant and premalignant lesions.

[Stiff-person syndrome: a case report]. / Síndrome de la persona rígida: a propósito de un caso.

INTRODUCTION: Stiff-person (stiff-man) syndrome is characterised by symptoms of muscular rigidity and spasms, which are generally of an axial nature. Involuntary contractions of the agonist and antagonist muscles caused by activity of the motor units during rest are the main clinical and electrophysiological marker of the disease. The nature of the syndrome is considered to be autoimmune, with positive glutamic acid decarboxylase (anti-GAD) antibodies in most patients. These antibodies exert an influence over GABAergic transmission. CASE REPORT: A 29-year-old female who was admitted to hospital with a diagnosis of psychogenic mutism. While in hospital the patient developed a clinical picture consisting in generalised stiffness that was predominantly axial and proximal with hyperreflexia in the four limbs and strong contraction of the muscles of the abdomen. The most striking lab finding was the presence of anti-GAD, anti-parietal cells, anti-microsomal/TPO and antithyroglobulin antibodies, together with oligoclonal immunoglobulin G bands in the cerebrospinal fluid. Treatment was established with benzodiazepines, antispastic agents and corticosteroids, and the clinical symptoms progressively improved until they had partially remitted at two months. The lab findings and clinical features are compatible with stiff-person syndrome in a patient with associated psychiatric comorbidity. CONCLUSIONS: Anti-GAD antibodies are not exclusive to stiff-person syndrome and can also be found in a number of other autoimmune disorders. Other mechanisms which can also produce a dysfunction of the GABAergic system have also been suggested. The syndrome can be difficult to diagnose from the clinical point of view and it must therefore be borne in mind in patients who begin with unexplainable stiffness and spasms because it is a potentially treatable pathology.