Levetiracetam following liver and kidney failure in late-onset anticonvulsant hypersensitivity syndrome.

Anticonvulsant hypersensitivity syndrome is an adverse drug reaction usually occurring from 1 to 8 weeks after exposure to antiepileptic drugs. It can threaten life by affecting the liver, kidneys, central nervous system or lungs. We present a 47-year-old patient treated with phenytoin, lamotrigine and clobazam for 7 years. He presented with hepatic and renal failure in relation to this syndrome demonstrated by renal biopsy. Prognosis was excellent due to an early diagnosis leading to cessation of the causative agents. Levetiracetam was started with a good response.

Hematopoyesis extramedular en paciente con esferocitosis hereditaria asintomática / Extramedullary hematopoiesis in patients with asymptomatic hereditry spherocytosis

En diversas patologías con alteraciones en la producción de los elementos formes de la sangre pueden desarrollarse focos de hematopoyesis extramedular en diferentes sitios. Los más frecuentes son: bazo, hígado, ganglios linfáticos, y más raramente otros órganos como: glándulas adrenales, hillios renales, cartílagos, ligamentos, tejido adiposo, timo, pulmón, mediastino y duramadre de cráneo y columna. Generalmente el proceso es difuso pero pueden formarse grandes tumores de tejido hematopoyético. Las condiciones patológicas de la médula ósea más frecuentemente asociadas a hematopoyesis extramedular son: esferocitosis hereditaria, talasemia, síndromes mieloproliferativos con fibrosis medular, ocupación medular por patologías neoplásicas. presentamos un paciente de 45 años con esferocitosis hereditaria con masas de tejido hematopoyético extramedular paravertebral mediastinal que respondieron favorablemente a la esplenectomía.(AU)

Hereditary spherocytosis (HS) is a relatively common inherited hemolytic disorder in northern Europe and in the US. The reported prevalence of HS in Western countries is 1:5000. We describe a patient 45 years old, with hereditary spherocytosis with masses of mediastinal paravertebral extramedullary hematopoietic tissue, with a favorable response to splenectomy. The medical lieterature refers some cases of extramedullary hematopoiesis as a clinical expression of hereditary spherocytosis, mainly as thoracic masses with usually paravertebral localization. HS should be distinguished from other spherocytic hermolytic anemias. Diagnosis is usually made uring infancy or in young adults, but it can be at any moment of their life, until the seventh decade of life. Ocasionally, the diagnosis is first made in old age. The clinical expression of HS is highly variable, ranging from asymptomatic condition to a severe life-threatening hemolytic anemia. Laboratory features include spherocytosis, osmotic fragility, manifestations of hemolytic disease, elevated unconjugated bilirubin and reticulocytosis. The principal diagnostic test, RBC osmotic fragility, measures the surface/volume Ratio of the cells. The treatment of choice of HS in patients with inherited spherocytosis is splenectomy, which corrects hemolytic anemia. According to he literature, cases of failure following splenectomy have been reported.(AU)

Hematopoyesis extramedular en paciente con esferocitosis hereditaria asintomática / Extramedullary hematopoiesis in patients with asymptomatic hereditry spherocytosis

En diversas patologías con alteraciones en la producción de los elementos formes de la sangre pueden desarrollarse focos de hematopoyesis extramedular en diferentes sitios. Los más frecuentes son: bazo, hígado, ganglios linfáticos, y más raramente otros órganos como: glándulas adrenales, hillios renales, cartílagos, ligamentos, tejido adiposo, timo, pulmón, mediastino y duramadre de cráneo y columna. Generalmente el proceso es difuso pero pueden formarse grandes tumores de tejido hematopoyético. Las condiciones patológicas de la médula ósea más frecuentemente asociadas a hematopoyesis extramedular son: esferocitosis hereditaria, talasemia, síndromes mieloproliferativos con fibrosis medular, ocupación medular por patologías neoplásicas. presentamos un paciente de 45 años con esferocitosis hereditaria con masas de tejido hematopoyético extramedular paravertebral mediastinal que respondieron favorablemente a la esplenectomía.

Hereditary spherocytosis (HS) is a relatively common inherited hemolytic disorder in northern Europe and in the US. The reported prevalence of HS in Western countries is 1:5000. We describe a patient 45 years old, with hereditary spherocytosis with masses of mediastinal paravertebral extramedullary hematopoietic tissue, with a favorable response to splenectomy. The medical lieterature refers some cases of extramedullary hematopoiesis as a clinical expression of hereditary spherocytosis, mainly as thoracic masses with usually paravertebral localization. HS should be distinguished from other spherocytic hermolytic anemias. Diagnosis is usually made uring infancy or in young adults, but it can be at any moment of their life, until the seventh decade of life. Ocasionally, the diagnosis is first made in old age. The clinical expression of HS is highly variable, ranging from asymptomatic condition to a severe life-threatening hemolytic anemia. Laboratory features include spherocytosis, osmotic fragility, manifestations of hemolytic disease, elevated unconjugated bilirubin and reticulocytosis. The principal diagnostic test, RBC osmotic fragility, measures the surface/volume Ratio of the cells. The treatment of choice of HS in patients with inherited spherocytosis is splenectomy, which corrects hemolytic anemia. According to he literature, cases of failure following splenectomy have been reported.

Gastrointestinal stromal tumors (GISTs) of the colon.

Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal tumors of the gastrointestinal (GI) tract. Although they may arise anywhere of GI tract, colonic presentation is infrequent. We report 2 new cases of colonic GISTs localized at descending and sigmoid colon. Endoscopic biopsies were diagnostic for GISTs and no distant metastasis were observed. Both cases underwent resective surgery as the only treatment. No recurrence was observed during the follow-up period. In this clinical note we review the diagnosis, management and therapeutical options in colonic GISTs, according to literature. KIT immunoreactivity is the base for diagnosis. Risk of malignancy is based on the primary tumor diameter and the mitotic count. Anatomic localization is not an independent prognostic factor. Surgery is the standard treatment for localized primary disease and imatinib is indicated if metastatic or unresectable GISTs.

Tumores del estroma gastrointestinal (GIST) del colon / No disponible

Los tumores del estroma gastrointestinal (GIST) son los tumores mesenquimales más comunes del tracto gastrointestinal (GI). Aunque pueden aparecer en cualquier localización del tracto GI, el colon no es una ubicación frecuente. Presentamos 2 nuevos casos de GIST de colon localizados en el colon descendente y el sigma. El diagnóstico histológico se obtuvo mediante biopsias endoscópicas. En ambos casos se realizó cirugía resectiva como único tratamiento. No se objetivó afectación metastásica en ningún caso. Tampoco se observó recurrencia durante el período de seguimiento. En esta nota clínica hemos revisado el diagnóstico, manejo y opciones terapéuticas en los GIST de colon. La inmunorreactividad para el c-kit es la clave para el diagnóstico. El riesgo de malignización se basa en el diámetro tumoral y el índice mitótico. La localización anatómica no parece ser un factor pronóstico independiente. La cirugía supone el tratamiento estándar en caso de enfermedad localizada, mientras que el imatinib está indicado en los GIST irresecables o con afectación metastásica(AU)

Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal tumors of the gastrointestinal (GI) tract. Although they may arise anywhere of GI tract, colonic presentation is infrequent. We report 2 new cases of colonic GISTs localized at descending and sigmoid colon. Endoscopic biopsies were diagnostic for GISTs and no distant metastasis were observed. Both cases underwent resective surgery as the only treatment. No recurrence was observed during the follow-up period. In this clinical note we review the diagnosis, management and therapeutical options in colonic GISTs, according to literature. KIT immunoreactivity is the base for diagnosis. Risk of malignancy is based on the primary tumor iameter and the mitotic count. Anatomic localization is not an independent prognostic factor. Surgery is the standard treatment for localized primary disease and imatinib is indicated if metastatic or unresectable GISTs(AU)

Cellular distribution of growth hormone-releasing hormone receptor in human reproductive system and breast and prostate cancers.

Growth hormone releasing hormone receptor (GHRH-R) mRNA and protein was first localized to the anterior pituitary gland, consequent with the action of its ligand on GH synthesis and release. Subsequent studies found GHRH-R also expressed in the hypothalamus and in systemic tissues including those of the reproductive system. In the present work, we studied the distribution of GHRH-R in human reproductive system of males and females by immunohistochemical method. GHRH-R immunostaining was localized in male reproductive system: Leydig cells, Sertoli and basal germ cells of the seminiferous tubules and prostate secretory cells. GHRH-R immunostaining was also demonstrated in the ovary: oocytes, follicular cells, granulosa, thecal and corpus luteum cells. Endometrial glands, placenta and normal mammary glands also showed GHRH-R immunostaining. Our results demonstrate the localization of GHRH-R in the reproductive system, which may mediate the direct action of GHRH in these tissues. Moreover, GHRH-R was demonstrated in prostate and breast carcinomas, opening a variety of possibilities for the use of GHRH antagonists in the treatment of prostatic and mammary tumors.

Reconstruction of soft-tissue defects of the heel with local fasciocutaneous flaps.

Soft tissue heel defects reconstruction represents a challenge for plastic surgeons because of the poor availability of regional tissue to perform the reconstruction. We divide the heel on the anterior or weight-bearing heel and the posterior or non-weight-bearing heel. Our preferences are the fasciocutaneous instep flap for anterior heel defects and the reverse sural flap for posterior heel defects. We have performed 11 reconstructions of the heel. The complications were total necrosis of 1 instep flap in a previously irradiated patient and 1 case of partial tip necrosis in a reverse sural flap. Functional recovery has been very satisfactory for both procedures. Regional island flaps are for us the first therapeutic option because the skin is similar to the lost one and less time consuming than a free-flap reconstruction.

MOC-31/Ep-CAM immunoreactivity in Merkel cells and Merkel cell carcinomas.

AIMS: To evaluate the monoclonal antibody MOC-31 in Merkel cell carcinomas and normal Merkel cells. Merkel cell carcinoma is a rare and aggressive tumour that occurs mainly in elderly individuals. The histological diagnosis of Merkel cell carcinoma can be difficult because it looks similar to other small blue cell tumours, particularly skin metastases of small-cell lung carcinomas. This antibody recognizes the epithelial cell adhesion molecule (Ep-CAM), that has been assigned to the small cell lung cancer cluster 2 of antibodies. To the best of our knowledge, immunostaining for MOC-31/Ep-CAM has not been previously described in Merkel cells or Merkel cell carcinomas. METHODS AND RESULTS: Thirty-one cases of Merkel cell carcinoma and three samples of normal human fingertip were selected to analyse the expression of MOC-31/Ep-CAM by immunohistochemistry. A high number of Merkel cell carcinomas (21/31, 67.7%) showed intense and readily interpretable positivity. Immunostaining was diffuse or focal and always localized to the plasma membrane. Normal Merkel cells of human fingertip also showed plasma membrane immunoreactivity for MOC-31/Ep-CAM. CONCLUSION: The demonstration of positivity for MOC-31/Ep-CAM in Merkel cell carcinomas precludes the use of this immunohistochemical marker to distinguish between tumours and skin metastases of small-cell lung carcinoma.

[Benign congenital myopathy associated with a partial deficiency of complexes I and III of the mitochondrial respiratory chain]]. / Miopatía congénita benigna asociada a deficiencia parcial de los complejos I y III de la cadena respiratoria mitocondrial.

INTRODUCTION: Isolated or combined enzyme deficiencies of the mitochondrial respiratory chain results in a number of clinical heterogeneous conditions. When presented in the neonatal period or early in the infancy the course is usually severe, although isolated cases with benign evolution have also been described. OBJECTIVE: To describe the clinical and biochemical characteristics of a child with a benign form of mitochondrial myopathy due to a combined deficiency of the complexes I and III of the respiratory chain. CLINICAL CASE: A 40 days-old male, the second son of a young non-consanguineous couple, presented with axial congenital hypotonia, asymmetrical macrocephaly, mild enlargement of the liver, mild coarsening of facial features, increased CK serum values, persistently elevation of serum lactate and lactate/pyruvate ratio and external hydrocephalus. Electromyogram and histological muscle examination were normal but analysis of the respiratory chain disclosed a deficiency of the complexes I and III. From 13 months-age onwards clinical detailed abnormalities progressively ameliorated and also did it serum CK, lactate and external hydrocephalus. CONCLUSION: We think that on clinical, basic biochemical and histological grounds there are some similarities between this case of congenital unspecific myopathy and benign reversible form of mitochondrial myopathy, arguing in favor of a possible relationship between both conditions.

Increased expression of growth hormone and prolactin receptors in hepatocellular carcinomas.

The liver is an essential target tissue for growth hormone (GH) and prolactin (PRL). The aim of this study was to determine the in situ expression of growth hormone receptor (GHR) and prolactin receptor (PRLR) in hepatocellular carcinomas and to compare the results with normal liver. For this purpose, in situ hybridization (ISH) and immunohistochemical techniques were performed and several tests were conducted to validate the results. By radioactive ISH, all the hepatocellular carcinomas studied showed labeling for GHR and PRLR mRNAs. Relative expression levels, determined by computer-assisted microdensity, were higher in hepatocellular carcinomas than in normal liver. Immunohistochemistry led us to confirm the constant expression of both receptor proteins in hepatocellular carcinomas and normal liver and to demonstrate their localization not only in the cytoplasm but also in the nucleus. These results confirm that the liver is a major GH and PRL target tissue and suggest that in hepatocellular carcinomas the proliferative effects of these hormones may be increased by a higher expression of their receptors.

Restricted presence of the growth hormone-releasing hormone receptor to somatotropes in rat and human pituitaries.

Specific binding of growth hormone-releasing hormone (GHRH) to its plasma membrane receptor represents the first step of cellular signals leading to exocytotic GH secretion in the anterior pituitary. The GHRH receptor (GHRH-R) has been cloned and belongs to the secretin/glucagon/vasoactive intestinal peptide subfamilly of G-protein-coupled receptors. To study its characteristics in rat and human pituitaries and examine its cellular and subcellular localization, a site-directed polyclonal antibody recognizing the C-terminal portion 392-404 of the rat and human GHRH-R was used. Immunohistochemistry was performed on paraffin-embedded pituitary sections while ultrastructural immunocytology was done on frozen and Lowicryl-resin-embedded ultrathin sections. GHRH-R-like immunoreactivity was restricted to somatotropes and colocalized with GH in both rat and human tissues. No signal was detected in gonadotropes, lactotropes, corticotropes and thyrotropes. At the subcellular level, gold particles were associated with the plasma membrane (observed on ultrathin frozen sections), secretory granule membrane, cytoplasmic matrix, nuclear membrane and nuclear matrix. In the nucleus, gold particles were mainly observed at the junction between eu- and heterochromatin. The highest density of labeling was observed in the cytoplasm (55 vs. 45% in the nucleus), mainly in secretory granules (59% of cytoplasmic labeling) and the plasma membrane. These results support the hypothesis that GHRH-mediated actions in the pituitary are specific to somatotropes and that GHRH-R isoforms and/or ligand-receptor complexes are involved in intracellular trafficking, recycling processes and nuclear functions.

Renal artery rupture secondary to pretransplantation Candida contamination of the graft in two different recipients.

Infected graft transplantation is an unwelcome complication that may lead to serious consequences in the immunosuppressed host. It can be caused by infection of the donor or by contamination of the organ during harvest, preservation and handling, or at transplantation. With current donor evaluation protocols, the risk of transmitting infections by exogenous contaminated grafts seems to be more frequent than true donor-transmitted infections. Nevertheless, although rare and usually free of clinically significant sequelae, if contamination is by some virulent organisms such as Staphylococcus aureus, gram-negative bacilli, or fungi, severe complications may occur. We report the clinical outcome of liver, heart, and kidney recipients from a single donor. Both renal allografts had to be removed because of renal artery rupture secondary to Candida albicans infection. Careful donor evaluation before transplantation, unusually early presentation of mycosis leading to anastomotic renal artery disruption, the histopathologic findings of the grafts, and the absence of Candida infection in the liver and heart recipients make us believe that exogenous contamination of the grafts occurred during donor procedure, kidney processing, or at transplantation. In summary, because infected grafts can lead to serious complications, besides careful donor screening, it is important to achieve early recognition of contaminated organs by culturing the perfusate to start specific antibiotic or antifungal therapy after transplantation if necessary and avoid the rare but, in this case, fatal consequences of these infections.

Voluntary ingestion of Cortinarius mushrooms leading to chronic interstitial nephritis.

'Magic mushrooms' ingestion among the drug-using population has become a popular cheap way to get hallucinogenic effects which is not free of complications. One of these is acute renal failure related to Cortinarius genus intake. This one greatly resembles 'magic mushrooms' and confusion is possible for inexperienced collectors. We report the case of a young male ex-drug addict who developed acute tubulointerstitial nephritis after voluntary ingestion of Cortinarius orellanus. The clinical picture was preceded by a long latency period, had an insidious course without any data of hepatoxicity and evolved to a chronic state. Renal biopsy showed nonspecific histopathological findings. In summary, it is important to bear this possibility in mind when facing an acute tubulointerstitial nephritis of unknown origin in a drug-taking patient.

Congenital ocular motor apraxia associated with myopathy, external hydrocephalus and NADH dehydrogenase deficiency.

Congenital ocular motor apraxia (COMA), first described by Cogan [Trans Am Acad Ophthalmol Otolaryngol 1952;56:853-862], is a rare disorder characterized by impairment of voluntary and optically induced horizontal eye movements and compensatory head thrust. The causes and pathogenesis of COMA are poorly understood. It frequently occurs in association with other neurologic abnormalities including non-progressive congenital disorders of the central nervous system (CNS), various systemic diseases and chromosomal alterations. Here, we report the case of a 6-month-old girl with psychomotor retardation, myopathy and clinical features of COMA, associated with external hydrocephalus and mitochondrial dysfunction (partial deficiency of the respiratory-chain enzyme NADH dehydrogenase). In view of this finding, we recommend that tests to characterize patients with COMA should include determination of blood levels of lactic and pyruvic acid.

Mesalazine-associated tubulo-interstitial nephritis in inflammatory bowel disease.

The 5-aminosalicylic acid (5-ASA) is currently the treatment of choice for patients with inflammatory bowel disease. It can be administered as sulfasalazine (5-ASA + sulfapyridine), mesalazine (5-ASA + resins or gels) and olsalazine (two molecules of 5-ASA). The recent trend has been to use formulations without sulfapyridine since they produce less side-effects although some cases of nephrotoxicity have been described. We report the case of a young female with Crohn's disease treated with mesalazine (400 mg every 8 hours) over a period of 12 months who developed acute interstitial nephritis. The characteristic features of renal function impairment were an insidious onset with non-specific laboratory data and progression towards a chronic state which partially improved with steroid treatment. In summary, it is important to bear this possibility in mind when confronted by any renal impairment which cannot be related to a relapse of inflammatory bowel disease. Renal function should be monitored routinely in patients receiving mesalazine at least during the first year of treatment and annually thereafter.

Cellular distribution of prolactin receptors in human digestive tissues.

In the present study we analyzed the expression of prolactin receptors (PRLR) in human digestive tissues by immunohistochemistry. PRLR immunoreactivity was primarily localized in the cytoplasm. However, in some organs (liver and salivary glands) a nuclear positivity was also found. The liver was used as control and showed a diffuse immunostaining in the parenchymal cells. In the gastrointestinal tract, PRLR immunoreactivity was observed in the mucosa, muscularis layer, and nervous plexuses. The more intense immunostaining in the mucosa of the different segments was as follows: esophagus, superficial layers of the stratified squamous epithelium and mucous glands; stomach, parietal cells; small intestine, absorptive and Paneth cells; and colon, surface epithelium and superficial half of the crypts of Lieberkühn. In the salivary glands, immunoreactivity was strong in the mucous tubules, moderate in the ducts, and weak in the serous cells. Endocrine pancreas showed a more intense immunoreactivity than the pancreatic acini. By serial sections of the islets of Langerhans we showed that immunostaining was confined to B cells. These findings demonstrate the widespread distribution of PRLR in human digestive tissues and its localization both in cytoplasms and nuclei.

Severe myoclonic epilepsy associated with mitochondrial cytopathy.

We describe a case in which severe myoclonic epilepsy of infancy is associated with a disturbance in mitochondrial function. EEG traces showed diffuse spike-wave patterns inducible by intermittent photic stimulation. Laboratory analyses revealed high lactic acid levels in cerebrospinal fluid and urine, without metabolic acidosis or high lacticacidaemia. Muscle biopsy showed a slight increase in the number of mitochondria, which had a tendency towards subsarcolemmal locations, and clefts in the myofibrillar membrane that contained granular material staining positive for oxidative enzymes and red with modified Gomori stain. Quantification of the enzymatic activities of homogenized muscle showed partial deficiency of the mitochondrial respiratory chain complexes III and IV. Severe myoclonic epilepsy associated with mitochondrial cytopathy was diagnosed, but the possibility cannot be ruled out that the myoclonic epilepsy (or perhaps simply nonspecific epileptic encephalopathy) was secondary to the mitochondrial cytopathy. Thorough diagnostic analysis in severe myoclonic epilepsy cases is called for with a view to elucidation of a possible metabolic aetiology.