IVIVC approach based on carbamazepine bioequivalence studies combination.

The aim of the present study was to explore the feasibility of obtaining an IVIVC by combination of data from two bioequivalence (BE) studies of carbamazepine (CBZ) in order to assess if the previously published dissolution media and conditions could be applicable to any other oral immediate release (IR) CBZ products with conventional excipients. Twenty-four healthy male subjects from two BE study received one IR dose of the test (test 1 or 2) or the reference formulation (Tegretol, 400 mg). Dissolution studies of the IR CBZ tablets were performed in two different laboratories. In order to develop IVIVC, individual or average data analysis were considered. A level C, level B and level A correlation have been successfully developed by combining data from different BE studies of CBZ immediate release drug products. A level A IVIVC was developed with all four datasets with a good R2 for all the combinations of in vivo and in vitro data. A dissolution medium containing 1% SLS has demonstrated its suitability as the universal biopredictive dissolution medium, even if different batches and in vivo/in vitro studies were combined.

[Results of the implementation of a protocol for outpatient management of the paediatric patient with tuberculosis]. / Resultados de la implantación de un protocolo para el manejo ambulatorio del paciente pediátrico con enfermedad tuberculosa.

OBJECTIVE: To assess the results of the implementation of a protocol for the outpatient management of paediatric patients with tuberculosis, and to compare it with the previous approach. MATERIAL AND METHODS: All patients younger than 14 years of age diagnosed with tuberculosis in Cantabria between 2005 and 2014 were included in the study. The pre-implementation period included patients admitted for gastric aspirate collection and to start treatment until 2010 (Pre-group). The post-implementation period was from 2010 onwards, using a protocol established for the outpatient management of these patients, with admission only being for clinical or social reasons, post-implantation period (Post-group). RESULTS: A total of 82 patients were studied: 29 from the Pre-group and 53 from Post-group. The median age was 61 months (IQR 32.5-97.75). All patients in the Pre-group were systematically admitted, compared to 26.4% of the Post-group (P<.001). The mean hospital stay was higher (7.27±7.1 days) in the Pre-group than in Post-group (3.4±11.46 days) (P<.0001). Only in 6.9% of patients from Pre-group were the 3 microbiological samples recommended for diagnosis following the international guidelines were provided, whereas they were provided by 73.58% patients from Post-group (P<.001). Of the cultures performed, 26.6% were positive for Mycobacterium tuberculosis, 37.5% of the Pre-group and 21.6% of the Post-group (P=.121). No significant differences were observed between the groups in other parameters related to treatment such as, therapeutic adherence, treatment not adjusted to the guidelines, treatment withdrawal or relapse.. DISCUSSION: Although guidelines recommend three microbiological samples for culture, no superior microbiological isolation was detected despite the increased number of samples collected. The management in hospital clinics of patients with suspected tuberculosis with stable clinical situation show similar or better clinical and microbiological results to the previous management, with lower hospital admission rate and with the subsequent cost savings.

[Verrucous carcinoma of the penis arising from a lichen planus. A true preneoplastic lesion?]. / Carcinoma verrucoso de pene desarrollado sobre un liquen plano. Una auténtica lesión preneoplásica?

INTRODUCTION: Up to 30% of squamous cell carcinomas of the penis arise from a lichen sclerosus, but very few reports in which lichen planus was the preexisting lesion have been published. We report a male with verrucous carcinoma of penis that developed in an area of lichen planus. CLINICAL CASE: A 53-year-old male presented with an exophytic tumor on the glans penis that had been present for about 6 months. The lesion developed in a previously biopsied area of lichen planus hypertrophicus. After excision, histological diagnosis was verrucous carcinoma. COMMENT: The development of any subtype of squamous cell carcinoma of penis in a lichen planus can be coincidental, or a neoplastic transformation of lichen planus can take place.

[Blood cultures in the paediatric emergency department. Guidelines and recommendations on their indications, collection, processing and interpretation]. / Hemocultivos en urgencias pediátricas. Guía práctica de recomendaciones: indicaciones, técnica de extracción, procesamiento e interpretación.

Blood culture (BC) is the gold standard when a bacteraemia is suspected, and is one of the most requested microbiological tests in paediatrics. Some changes have occurred in recent years: the introduction of new vaccines, the increasing number of patients with central vascular catheters, as well as the introduction of continuous monitoring BC systems. These changes have led to the review and update of different factors related to this technique in order to optimise its use. A practice guideline is presented with recommendations on BC, established by the Spanish Society of Paediatric Emergency Care and the Spanish Society for Paediatric Infectious Diseases. After reviewing the available scientific evidence, several recommendations for each of the following aspects are presented: BC indications in the Emergency Department, how to obtain, transport and process cultures, special situations (indications and interpretation of results in immunosuppressed patients and/or central vascular catheter carriers, indications for anaerobic BC), differentiation between bacteraemia and contamination when a BC shows bacterial growth and actions to take with a positive BC in patients with fever of unknown origin.

[Primary non-Hodgkin large B-cell lymphoma of bladder. Report of a case]. / Linfoma no hodgkin B de célula grande primario de vejiga. Presentación de un caso.

INTRODUCTION: primary genitourinary lymphomas are uncommon. Among them, bladder lymphomas are extremely unusual tumors, with clinico-radiological features similar to urothelial carcinomas of bladder. Histopathological, immunohistochemical and molecular studies are compulsory for the diagnosis. We report a case of this tumor. CLINICAL CASE: An 80-year-old woman was admitted to our hospital with hematuria. Abdominal ultrasound and cystoscopy revealed an infiltrating bladder tumor involving the right lateral wall. After transuretral biopsy, a diagnosis of non-Hodgkin large B-cell lymphoma was made. Neither clinical symptoms nor radiological findings showed disseminated disease, indicating that the tumor was localized in the bladder. After chemotherapy, the patient is disease-free after 9 months follow-up. COMMENT: if a bladder tumor with uncommon histopathological features is found, lymphoma should be excluded, because chemotherapy avoids cystectomy.

[Steroid treatment: risk factor for invasive pulmonary aspergillosis]. / Tratamiento esteroide: factor de riesgo para aspergilosis pulmonar invasiva.

To describe the association between invasive pulmonary aspergillosis and steroid treatment in patients with no immunodepression attributable to other causes. We reviewed the case histories of apparently non immunodepressed patients in our hospital with histological diagnoses of invasive pulmonary aspergillosis between 1992 through 1996. Seven patients were identified. Laboratory, clinical and radiological data were collected, as well as type and duration of steroid treatment. Four patients suffered underlying chronic obstructive pulmonary disease, 1 had temporal arteritis, 1 interstitial pulmonary fibrosis and 1 a neurological tumor. All had received steroid treatment for periods varying from several days to 16 months, at varying doses, although the majority of them were treated with 1mg/kg/day. All presented clinical profiles suggestive of pneumonia (5 community acquired and 2 nosocomial). Invasive pulmonary aspergillosis can appear in minimally immunocompromised patients, such as those undergoing steroid treatment and must be suspected whenever pneumonia is seen in patients receiving steroids who do not improve with widespectrum antibiotic treatment.

[Diffuse xanthogranulomatous pyelonephritis with a renocolic fistula neglected for more than two years]. / Pielonefritis xantogranulomatosa difusa con fistula renocólica inadvertida durante más de dos años.

INTRODUCTION: Although reno-colic fistula is a well-known complication of the diffuse form of xanthogranulomatous pyelonephritis, the features of the case here presented are unusual because of the paucity of symptoms and long lasting evolution of the disease before it was diagnosed. CLINICAL CASE: A 75 year-old woman was seen at the emergency room complaining of fever and malaise. Physical and laboratory examination showed anemia and a left abdominal mass, and on X-ray and abdominal CT, a gross stone and huge left renal and extrarenal xanthogranulomatous pyelonephritis with renocolic fistula were disclosed. A review of her clinical record showed an X-ray performed two years before by the attending family clinician, with identical gross calculi and gas into the kidney. Nephrectomy, caudal pancreatectomy and partial colectomy were accomplished with good results. COMMENT: This case of poor-symptomatic xanthogranulomatous pyelonephritis that destroyed the kidney and induced a renocolic fistula, is unusual because it was neglected for more than two years due to unawareness of the clinical and radiological picture.

[Mucinous adenocarcinoma of the urachus synchronic with colorectal adenocarcinoma. Value of immunohistochemistry in the differential diagnosis]. / Adenocarcinoma mucinoso de uraco sincrónico con adenocarcinoma colorrectal. Valor de la inmunohistoquímica en el diagnóstico diferencial.

The coincidence of an urachal adenocarcinoma with another similar tumour in other location makes necessary to separate a true primary from a metastatic adenocarcinoma. We report the case of a 66-years-old-man with an urachal mucinous adenocarcinoma and two colonic adenocarcinoma excised in the same surgical act, showing both macro and microscopic studies together with immunohistochemical techniques, that were useful to differentiate the origin of both neoplasms. Among them, the antibody to keratin 7, a cytoplasmic epithelial protein, was positive in the urachal and negative in the colonic tumour.

[Coordinated expression of cytokeratin 7 and 20 in transitional carcinoma of the bladder: diagnostic usefulness]. / Expresión coordinada de citoqueratinas 7 y 20 en el carcinoma transicional de vejiga: utilidad diagnóstica.

BACKGROUND: Cytokeratins are intermediate filament proteins which are part of the framework of eucariotic cells. A characteristic pattern of expression of cytokeratins has been described for each type of epithelium. This pattern is maintained during the process of malignancy and metastasis. Immunohistochemical analysis of cytokeratins 7 and 20 (Ck 7 and Ck 20) has been considered particularly useful for identifying the origin of carcinomas. METHODS: A total of 122 cases of transitional cell carcinoma of urinary bladder were studied immunohistochemically with monoclonal antibodies against Ck 7 and Ck 20. The peroxidase labelled-streptavidin biotin technique was performed. Cases were considered positive when at least 1% of tumoral cells were stained. RESULTS: All cases investigated expressed Ck 7 whereas Ck 20 was positive in 75% of them. Reactivity for Ck 20 was always focal. No tumor was negative for Ck 7. CONCLUSION: Ck 7+/Ck 20+ immunophenotype is highly characteristic of transitional cell carcinoma of urinary bladder, whereas Ck 7+/Ck 20- is less frequent. Immunohistochemical determination of these cytokeratins is useful for the diagnosis when tumors are poorly differentiated and for identifying the primary site of metastatic carcinomas.

[Expression of CDX2 in urinary bladder and urethra lesions]. / Expresión de CDX2 en lesiones de vejiga urinaria y uretra.

BACKGROUND: CDX1 and CDX2 are transcription factors involved in the development and maintenance of the intestinal epithelial cell. Expression of CDX2 has been reported in normal and metaplastic intestinal epithelium, and in those adenocarcinomas with that cellular origin. We have analyzed the expression of this marker in reactive and tumoral lesions arising in urinary bladder, urethra and urachus. METHOD: CDX2 was investigated through immunohistochemistry on paraffin-embedded tissue, using the labelled streptavidin-biotin method (LSAB2, Dako) with a monoclonal antibody (CDX2-88, BioGenex). RESULTS: Expression of CDX2 was observed in intestinal-type cistitis glandularis, intestinal metaplasia of urinary bladder, bladder adenocarcinoma, mucinous urothelial-type carcinoma of prostatic urethra and urachal mucinous carcinoma. CDX2 was not detected in normal urothelium and prostatic glandular epithelium, Von Brunn nests, typical-type cistitis glandularis, glandular adenosis and transitional carcinoma. CONCLUSIONS: Lesions, both benign and malignant, with enteric-cell morphological features show positivity for CDX2. Expression of this marker is not organ-specific but is just related to a cellular phenotype. Reactivity for CDX2 in an adenocarcinoma can be consistent with an origin in urinary tract or urachus.

[Hyperplasia of adrenal rests in the testicle: a rare cause of male infertility]. / Hiperplasia de restos adrenales en el testículo: una causa infrecuente de infertilidad masculina.

We report the case of a 37-year-old man with infertility caused by bilateral testicular masses secondary to congenital adrenal hyperplasia (21-hydroxylase deficiency). Testicular biopsy was done and its was initially interpreted as Leydig cell tumor but after clinical information was histologically reclassified as tumor of the adrenogenital syndrome. The differential diagnosis with Leydig cell tumor is discussed and it must be established through the clinical, biochemical, radiological and pathological features.

["Evanescent" prostate carcinoma]. / Carcinoma "evanescente" de la próstata.

Occurrence of prostatectomy sections with minimum or no tumour volume have been increasingly seen over the last few years in spite of a preoperative histology-based diagnosis of adenocarcinoma with a needle biopsy ("evanescent cancer phenomenon" ECP). Our group has reviewed 145 prostatectomies performed in our hospital between January 1988 and October 1997, and found 3 cases of ECP (2%). To explain this phenomenon patients must be divided into two groups. In those who receive preoperative hormonal blockade, treatment may result in a drastic reduction of tumoral volume as well as microscopic changes that make malignancy recognition more difficult. ECP occurs in less than 5% of these prostatectomies. In patients with no previous hormonal treatment, ECP is extremely rare and any explanation comes as a consequence of the extended use of screening methods that lead to the detection of very small tumours, probably of little clinical relevance, that are found in the needle biopsy. Subsequently, however, no residual neoplasia is seen in the section either due to technical limitations of the pathoanatomical methods or because of a true, complete ablation of the lesion through the biopsy.

[Comparative study of the expression of p53, Ki-67, bcl-2 and CK20 in superficial transitional carcinoma of the bladder: correlation with recurrence, histological grade, and clinical stage]. / Estudio comparativo de la expresión de p53, Ki67, bcl-2 y CK20 en el carcinoma transicional superficial de vejiga: correlación con la recurrencia, grado histológico y estadio clínico.

OBJECTIVE: We examined the presence of p53, Ki-67, bcl-2 and CK20, as detected by immunohistochemistry, and correlated with the classic variables (grade, stage and recurrence). MATERIAL AND METHOD: The authors evaluated 57 superficial transitional cell carcinomas. Biopsy specimens examined included non recurrent transitional cell carcinomas (n = 36) and recurrent transitional cell carcinomas (n = 21). Association of bcl-2, p53, Ki-67 y CK20 index immunoreactivity with tumor grade, clinical stage and tumor recurrence was examined. RESULTS: Ki-67 and p53 expression were related to the degree of differentiation and recurrence of the disease. bcl-2 and CK20 were not correlated with grade, stage and recurrence of the disease. CONCLUSIONS: Positivity for Ki-67 and p53 increase with grade of the disease. P53 and Ki-67 are predictors of tumor recurrence for patients with superficial transitional cell carcinoma.

Impact of the Xpert(®) MTB/RIF molecular test on the late diagnosis of pulmonary tuberculosis.

We analysed the impact of the Xpert(®) MTB/RIF molecular test on health-care diagnostic delay among tuberculosis patients. Diagnostic delay was 17.2 days (standard deviation 23.2, median 10 days). Of 128 patients recruited into the study, 60 (47%) were smear-negative; of these, 40 (67%) were Xpert-positive and were started on treatment without culture. The sensitivity of smear microscopy was 53% compared with 82% for Xpert. In smear-negative patients, delay in Xpert-positive and -negative patients was respectively 15.5 ± 13.2 and 25.5 ± 12.5 days (P = 0.002). We conclude that Xpert results were significantly associated with shorter health-care diagnostic delay, particularly in smear-negative patients.

Necrotising pneumonia caused by Lactococcus lactis cremoris.

Lactococcus lactis cremoris is a facultative anaerobic, gram-positive coccus whose natural host is bovine livestock. It may form part of the normal human bacterial flora found in the oropharynx, the gastrointestinal tract and the vagina. This bacterium is essential in the food industry, where it is used in milk fermentation to obtain cheese, yoghurt, etc. Exposure to unpasteurised dairy products has thus been recognised as a risk factor for infection by this organism. It is generally considered to be non-pathogenic, although it appears that pathogenicity may be emerging. We present an atypical case of necrotising pneumonia caused by L. lactis cremoris.

Primary pulmonary botryomycosis: a bacterial lung infection mimicking lung cancer.

Primary pulmonary botryomycosis, or bacterial pseudomycosis, is an unusual bacterial infection characterised by the formation of eosinophilic granules that resemble those of Actinomyces species infection. The diagnosis of botryomycosis is based on culture of the granules revealing gram-positive cocci or gram-negative bacilli. The bacterial pathogen most frequently found is Staphylococcus aureus. The pathobiology remains unknown. Pulmonary botryomycosis can resemble actinomycosis, tuberculosis or invasive carcinoma. Definitive treatment requires a combination of both surgical debridement and long-term antimicrobial therapy. We present a case of primary pulmonary botryomycosis in an immunocompetent patient.

[Description of tuberculosis outbreak and usefulness of mediastinal ultrasound]. / Descripción de un brote de tuberculosis y utilidad de la ecografía mediastínica.

OBJECTIVES: Describe a school outbreak of tuberculosis and compare the features with other outbreaks. Propose mediastinal ultrasound as an aid in its diagnosis and monitoring. PATIENTS AND METHODS: Retrospective descriptive study of the transmission of tuberculosis infection in a micro-epidemic. Infection criteria: Mantoux ≥ 5mm, asymptomatic patient, with normal radiological, microbiological and analytical studies. Disease criteria: Mantoux ≥ 5mm and any of the above pathological studies. Mediastinal ultrasound was used as a complementary method of chest radiography (CXR). Computed tomography (CT) as the combined result of ultrasound and CXR was inconclusive. RESULTS: Seventeen out of 412 students were infected and 16 with tuberculosis disease. In addition, 4 out-school contacts were diagnosed of tuberculosis. CLINICAL MANIFESTATIONS: one erythema nodosum, one Henoch-Schönlein purpura, twelve with cough and fever nine. CXR results in patients: 3 normal, 7 inconclusive, and 10 with the following findings: 2 pneumonia, 2 pulmonary atelectasis, 2 primary complexes, 4 patients only with lymphadenopathy. All patients with normal or indeterminate CXR showed mediastinal lymphadenopathy visualized on ultrasound but 3 demonstrated by CT. Microbiological isolation: 6 cases (31%). CONCLUSIONS: The number of infected patients was higher compared to other outbreaks There is great variability in the diagnostic approach to tuberculosis micro-epidemics. It is complex to differentiate between infection and disease. The clinical, laboratory and CXR are nonspecific. There are patients with normal CXR, pathological ultrasound and microbiological isolation. Mediastinal ultrasound can play an important role in the diagnosis and management of tuberculosis disease.