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Bleeding is a frequent complication after allogeneic haematopoietic stem cell transplantation (HSCT) and may affect survival. The purpose of this study was to determine the incidence and risk factors for life-threatening bleeding after HSCT by retrospective evaluation of 491 allogeneic HSCT recipients. With a median follow-up of 33 months, 126 out of 491 allogeneic HSCT recipients experienced a haemorrhagic event (25·7%) and 46 patients developed a life-threatening bleeding episode (9·4%). Pulmonary and gastrointestinal bleeding were the most common sites for life-threatening bleeding, followed by central nervous system. In multivariate analyses, the presence of severe thrombocytopenia after day +28 and the development of grade III-IV acute graft-versus-host disease (GVHD) or thrombotic microangiopathy (TMA) retained their association with life-threatening bleeding events. The overall survival at 3 years among patients without bleeding was 67·1% for only 17·1% for patients with life-threatening bleeding (P < 0·001). In conclusion, life-threatening bleeding is a common complication after allogeneic HSCT. Prolonged severe thrombocytopenia, acute grade III-IV GVHD and TMA were associated with its development., (© 2015 John Wiley & Sons Ltd.)

Background: Relapsed or refractory (R/R) classical Hodgkin lymphoma (cHL) after autologous stem cell transplantation (ASCT) remains a challenge. For these patients treatments with different mechanisms of action rather than classical chemotherapy are needed., Patients and Methods: Patients with R/R cHL after ASCT were recruited in a phase II trial (EUDRA CT: 2009-016588-12). Lenalidomide was administered at 20 mg/day for 21 days and cyclophosphamide at 50 mg/day for 28 days (cycles every 28 days). Dose escalation for lenalidomide was permitted. In 2009 we considered that this treatment would be promising if response rate were over 60% and a Simon two-stage binomial design was used to calculate the sample size. A total of 46 patients were planned but the trial would be stopped if less than seven responses after four cycles were obtained in the first 16 patients., Results: The trial was closed early because only five responses were observed after four cycles in the first 16 patients included. Median age was 34 years (18-77). The median number of previous lines was five (2-6). At inclusion, 10 patients were primary refractory and 11 refractory to the last therapy. A total of 110 cycles were administered, with grade≥3 toxicity in 43 cycles (39%). One non-neutropenic patient developed septic shock resulting in death. An ORR of 38% (1 CR and 5 PR) was observed and a total of 10 patients (62%) achieved clinical benefit. Median progression free survival and overall survival were seven and 19 months, respectively. With a median follow-up of 19 months (3-38+), three-year progression-free and overall survival were 6% and 31%, respectively., Conclusion: The optimistic assumptions of this trial led to an early closure. However, the promising clinical benefit observed with the oral combination of lenalidomide and metronomic cyclophosphamide may justify its use for outpatient palliative treatment.

Field spectroradiometers integrated in automated systems at Eddy Covariance (EC) sites are a powerful tool for monitoring and upscaling vegetation physiology and carbon and water fluxes. However, exposure to varying environmental conditions can affect the functioning of these sensors, especially if these cannot be completely insulated and stabilized. This can cause inaccuracy in the spectral measurements and hinder the comparison between data acquired at different sites. This paper describes the characterization of key sensor models in a double beam spectroradiometer necessary to calculate the Hemispherical-Conical Reflectance Factor (HCRF). Dark current, temperature dependence, non-linearity, spectral calibration and cosine receptor directional responses are modeled in the laboratory as a function of temperature, instrument settings, radiation measured or illumination angle. These models are used to correct the spectral measurements acquired continuously by the same instrument integrated outdoors in an automated system (AMSPEC-MED). Results suggest that part of the instrumental issues cancel out mutually or can be controlled by the instrument configuration, so that changes induced in HCFR reached about 0.05 at maximum. However, these corrections are necessary to ensure the inter-comparison of data with other ground or remote sensors and to discriminate instrumentally induced changes in HCRF from those related with vegetation physiology and directional effects.

We report a nonlinearity effect related to the integration time in a double-beam spectroradiometer equipped with two negative-module metal-oxide semiconductor (NMOS) sensors. This effect can be explained by the addition of photoelectrons produced by the radiant flux on the sensors during the readout phase to the photoelectrons produced during the measurement phase. A new method is proposed to characterize and correct both gray-level and integration-time-related nonlinearities in NMOS sensors. This method is experimentally simple and outperforms other commonly used correction procedures.

The management of relapsed or refractory Hodgkin's lymphoma (RR-HL) remains a challenge for hematologists and oncologists. Salvage chemotherapy followed by autologous stem cell transplantation (ASCT) is the standard of care for RR-HL. However, one of the most controversial aspects is which the best salvage protocol could be. We retrospectively analyzed 82 consecutive RR-HL who received etoposide, steroids, ara-C, and cisplatin (ESHAP) as salvage therapy followed by ASCT. Fifty percent of patients were refractory and 23 % early relapses. Overall response rate (ORR) was 67 % (50 % complete remission (CR)). Ninety one percent of patients (75/82) were transplanted. With a mean follow-up of 87 ± 53 months, the median progression-free survival (PFS) and time to tumor progression (TTP) for the whole population were 52 and 56 months, respectively, and the 5-year overall survival was 72.6 %. Achieving CR after ESHAP was associated with a longer PFS (78 vs 16 % 5-year PFS, respectively, P < 0.01) and TTP (80 vs 19 % 5-year TTP, respectively, P < 0.01). However, there were no differences for overall survival (OS) when comparing CR and partial response (PR) after ESHAP. Toxicity was low and <10 % of patients developed neutropenic fever, with no toxic deaths. Mobilization was possible in 94 % of patients. ESHAP is a safe and efficient therapeutic option for patients with RR-HL who are candidates for ASCT, since it combines a high response rate and mobilizing potential with a low toxicity profile.

Bone marrow (BM) examination is included in the diagnostic algorithm of fever of unknown origin (FUO), although its role is not clearly determined. The purpose of this study was to assess the role of BM studies in patients with FUO. We retrospectively reviewed 45 consecutive patients (25% human immunodeficiency virus-positive) with FUO who underwent a BM study in the University Hospital of Salamanca from 2000 to 2010. We analysed the diagnostic role of BM smears, multiparameter flow cytometry analysis, histology and microbiological cultures. Five patients (11%) were finally diagnosed by BM study (three had an infectious disease and two were found to have haematological malignancies), all of whom were immunocompetent patients. Histology was the most useful study (diagnosis was obtained in 4/5 patients), while BM cultures did not establish the final diagnosis in any patient. Flow cytometry established the diagnosis in one patient, although this patient was also diagnosed by histology. In conclusion, BM study is useful for establishing the aetiology of FUO. BM biopsy for histological examination should be always mandatory if a BM examination is performed., (© 2014 The Authors; Internal Medicine Journal © 2014 Royal Australasian College of Physicians.)

Transplantation-associated thrombotic microangiopathy (TA-TMA) is a feared complication of allogeneic hematopoietic SCT (HSCT) owing to its high mortality rate. The use of calcineurin inhibitors or sirolimus (SIR) for GVHD prophylaxis has been suggested as a potential risk factor. However, the impact of tacrolimus (TAC) and SIR combinations on the increased risk of TA-TMA is currently not well defined. We retrospectively analyzed the incidence of TA-TMA in 102 allogeneic HSCT recipients who consecutively received TAC plus SIR (TAC/SIR) (n=68) or plus MTX (TAC/MTX)±ATG (n=34) for GVHD prophylaxis. No significant differences were observed in the incidence of TA-TMA between patients receiving TAC/SIR vs TAC/MTX±ATG (7.4% vs 8.8%, P=0.8). Only grade III-IV acute GVHD, previous HSCT and serum levels of TAC >25 ng/mL were associated with a greater risk of TA-TMA. Patients developing TA-TMA have significantly poorer survival (P<0.001); however, TA-TMA ceased to be an independent prognostic factor when it was included in a multivariate model. In conclusion, the combination of TAC/SIR does not appear to pose a higher risk of TA-TMA. By contrast, we identified three different risk groups for developing TA-TMA.

Kikuchi's disease, also known as histiocytic necrotizing lymphadenitis, is a rare, benign, and self-limited disorder of unknown cause that is usually characterized by cervical lymphadenopathy and fever. The etiology and pathogenesis remain unknown, but the clinical presentation, course, and histologic changes suggest an immune response of T cells and histiocytes to an infectious agent. Numerous inciting agents have been proposed. However, the association between human herpesvirus 7 and Kikuchi's disease has been rarely reported as a possible etiologic agent of Kikuchi's disease. We report the case of a 24-year-old Caucasian female patient with cervical lymphadenopathy and isolated pruriginous maculo-papular lesions who was diagnosed of Kikuchi's disease in whom the presence of human herpesvirus 7 DNA was documented in the affected lymph node specimen in the absent of other viruses. Therefore, a possible etiologic relation between the Kikuchi's disease of this patient and human herpesvirus 7 was established, supporting a role for human herpesvirus 7 involvement in the pathogenesis.

Allogeneic hematopoietic stem cell transplantation recipients have an increasing risk of both hemorrhagic and thrombotic complications. However, the competing risks of two of these life-threatening complications in these complex patients have still not been well defined. We retrospectively analyzed data from 431 allogeneic transplantation recipients to identify the incidence, risk factors and mortality due to thrombosis and bleeding. Significant clinical bleeding was more frequent than symptomatic thrombosis. The cumulative incidence of a bleeding episode was 30.2% at 14 years. The cumulative incidence of a venous or arterial thrombosis at 14 years was 11.8% and 4.1%, respectively. The analysis of competing factors for venous thrombosis revealed extensive chronic graft-versus-host disease to be the only independent prognostic risk factor. By contrast, six factors were associated with an increased risk of bleeding; advanced disease, ablative conditioning regimen, umbilical cord blood transplantation, anticoagulation, acute III-IV graft-versus-host disease, and transplant-associated microangiopathy. The development of thrombosis did not significantly affect overall survival (P=0.856). However, significant clinical bleeding was associated with inferior survival (P<0.001). In allogeneic hematopoietic stem cell transplantation, significant clinical bleeding is more common than thrombotic complications and affects survival.

Early and rapid detection of the causative organism is necessary in tuberculosis. We present here an integrated and dedicated molecular biology system for tuberculosis diagnosis. One hundred and eighty-nine (189) biologic specimens from patients strongly suspected by clinical parameters of tuberculosis were studied by Ziehl-Neelsen staining, cultivation on a solid medium, and by a balanced heminested fluorometric PCR system (Orange G3TB) that preserves worker safety and produces a rather pure material free of potential inhibitors. DNA amplification was carried out in a low cost using a tuberculosis thermocycler-fluorometer. The double stranded DNA produced is fluorometrically detected. The whole reaction is carried out in one single tube which is never opened after adding the processed sample, thus minimizing the risk of cross contamination with amplicons. The assay is able to detect 30 bacilli/ml of sample having a 99.8 % inter-assay coefficient of variation. PCR was positive in 36 (18.9 %) tested samples (33 of them were smear-negative). In our study, it yields a preliminary overall sensitivity of 97.4 %. In addition, its overall specificity is 98.7 %. The total run time of the test is 4 h with two and a half real working hours. All PCR-positive samples also had a positive result by microbiological culture and clinical criteria. The results obtained showed that it could be a very useful tool to increase efficiency in detecting the tuberculosis disease in low bacillus inoculum samples. Furthermore, its low cost and friendly usage make it feasible to be used in regions with poor development.

We describe the results of an experiment designed to compare the radiometric performance of four different spectroradiometers in ideal field conditions. A carefully designed experiment where instruments were simultaneously triggered was used to measure the Hemispherical Conical Reflectance Factors (HCRF) of four targets of varying reflectance. The experiment was in two parts. Stage 1 covered a 2 hour period finishing at solar noon, where 50 measurements of the targets were collected in sequence. Stage 2 comprised 10 rapid sequential measurements over each target. We applied a method for normalising full width half maximum (FWHM) differences between the instruments, which was a source of variability in the raw data. The work allowed us to determine data reproducibility, and we found that lower-cost instruments (Ocean Optics and PP Systems) produced data of similar radiometric quality to those manufactured by Analytical Spectral Devices (ASD -here we used the ASD FieldSpec Pro) in the spectral range 400-850 nm, which is the most significant region for research communities interested in measuring vegetation dynamics. Over the longer time-series there were changes in HCRF caused by the structural and spectral characteristics of some targets.

All-trans retinoic acid (ATRA) induces complete remission in 64-100 % of patients with acute promyelocytic leukemia (APL), and is considered to be a safe agent. Pseudotumor cerebri is a neurological side effect of ATRA reported in pediatric patients, and which is characterized by raised cerebrospinal fluid pressure in the absence of any intracranial pathology or secondary causes of intracranial hypertension. Involvement of cranial nerves other than II and VI is very uncommon in idiopathic intracranial hypertension (IIH); peripheral facial nerve palsy is exceptional and has rarely been described in the context of treatment with ATRA. We describe the case of a 15-year-old female patient with APL who developed an IIH and involvement of cranial nerves (bilateral papilledema, left facial and right sixth nerves) after receiving induction therapy including ATRA. Viral infections and other causes of secondary cranial nerve lesions were excluded. Symptoms completely subsided with the temporary withdrawal of ATRA and did not recur after reintroducing the drug. To date, the patient has managed to receive the treatment as per protocol. In conclusion, we report an atypical presentation of IIH that merits consideration, especially with respect to young patients with APL receiving ATRA; our most important observation is that the drug could be safely reintroduced once the symptoms had resolved.

Scleromyxedema (SM) is a rare primary cutaneous inflammatory mucinosis characterised by papular mucinosis, monoclonal gammopathy and extracutaneous involvement. Most therapeutic options have failed in SM but high-dose therapy followed by autologous peripheral blood stem cell transplantation (APBSCT) appears to be highly effective, although SM normally relapses. We report the case of a 29-yr-old patient with severe SM who achieved stringent complete response with Bortezomib plus Dexamethasone after an early relapse subsequent to a high-dose melphalan regimen followed APBSCT. It is of particular note that dermatological lesions responded to both therapies before M-component modifications, suggesting that SM is independent of M-component characteristics. However, treatment should be directed towards the underlying plasma cell malignancy with typical anti-myeloma agents., (© 2012 John Wiley & Sons A/S.)

Objective: To present an integrated molecular biology dedicated system for tuberculosis diagnosis., Methods: One hundred and five sputum specimens from patients strongly suspected by clinical parameters of tuberculosis were studied by Ziehl-Neelsen staining, by cultivation on solid medium and by a balanced heminested fluorometric PCR system (Orange G3TB) that could preserve worker safety and produce a rather pure material free of potential inhibitors. DNA amplification was performed in a low cost tuberculosis termocycler-fluorometer. Produced double stranded DNA was flurometrically detected. The whole reaction was conducted in one single tube which would not be opened after adding the processed sample in order to minimize the risk of cross contamination with amplicons., Results: The assay was able to detect 30 bacillus per sample mL with 99.8% interassay variation coefficient. PCR was positive in 23 (21.9%) tested samples (21 of them were smear negative). In our study it showed a preliminary sensitivity of 94.5% for sputum and an overall specificity of 98.7%., Conclusions: Total run time of the test is 4 h with 2.5 real working time. All PCR positive samples are also positive by microbiological culture and clinical criteria. Results show that it could be a very useful tool to increase detection efficiency of tuberculosis disease in low bacilus load samples. Furthermore, its low cost and friendly using make it feasible to run in poor regions.

Drug consumption is among the non-occlusive causes of ischemic colitis. We report a case of cocaine-induced ischemic colitis in a 34-year-old man who had undergone sigmoid resection and loop colostomy due to abdominal-pelvic injury 3 months previously. The patient presented with abdominal pain associated with diarrhea and slight transient fever of doubtful etiology and reported intranasal cocaine consumption. He was hemodynamically stable and showed no peritoneal irritation. Traces of blood were found in the colostomy bag. Colonoscopy showed ulcers and necrosis proximal to the stoma. Computed tomography angiography scan showed no abnormalities except filiform inferior mesenteric artery. The symptoms were self-limiting and the patient was discharged 3 days after admission. Subsequently the colostomy was closed without complications. A high degree of suspicion is required in young patients with abdominal pain not identified by conventional methods and a recent history of drug consumption., (Copyright © 2010 Elsevier España, S.L. All rights reserved.)

Background: Chronic renal failure is becoming a public health problem. The estimation of glomerular filtration rate (GFR) using the MDRD-4 equation is important to find out patients with impaired renal function. The aim of this study was to determinate the rate of patients took care in Primary Care with "occult" renal failure, defined as a GFR less than 60 mL/min/1.73m2, and serum creatinine levels in the normal range of the laboratory (< 1.3 mg/dL for men, and < 1.2 mg/dL for women)., Methods: Patients over 18 years-old took cared in Primary Care of the health area of Plasencia (Caceres), who were measured serum creatinine level between March to July 2006. We estimated GFR using MDRD-4 formula and classified the level of kidney function according to the NKF-DOQI guidelines., Results: We estimated GFR in 13.784 analyses. In 1.042 the GFR was less than 60 mL/min/1.73m2, from 960 patients (6.96%). Mean age 76.8 years (range 40-98 years). 418 keep normal serum creatinine levels (43.5%)., Conclusion: Renal impairment seems to be prevalent in the general population took care in Primary Care. An elevated rate of patients with renal failure present serum creatinine levels in the laboratory normal range, "occult" renal failure. The systematic estimation of GFR using MDRD formula is necessary to detect this patients with renal impairment.

Sewage sludge production has significantly increased during the last years in European Union (EU) countries, being primarily used for agricultural purposes. In this study, digested sewage sludge was applied to greenhouse soil over a three-year period (2001--2003), with three sludge treatments in the first two years (2, 4, and 6 kg m(-2)) and three more applications using a greater quantity in the last year (6, 8, and 10 kg m(-2)). The effects of sewage sludge application on soil and on a leafy crop (Lactuca sativa L.) were studied. Mineral elements, organic matter, pH, and heavy metals were measured in soil and plant tissues. Pathogen and indicator microorganism dynamics in soil were also determined after each sludge application. Results showed that sewage sludge applications increased organic matter, P, and N Ca content in soil. Furthermore, Zn, Pb, Ni, and Cu content increased in soils, primarily after high doses of sludge. The highest yield value was obtained in the second-year harvest, since the last sludge application did not increase yield. Fecal coliform numbers decreased significantly one month after sludge application. However, total coliforms, Clostridium sulphite-reducers and Salmonella, were present in soils three months after sludge application.

Introduction: Post-ischemic brain edema occurs in 10-20% of cases of infarction of the middle cerebral artery and is the main cause of early death following a completed stroke. This complication, which is known as malignant middle cerebral artery infarction (MMCI), has a mortality rate of 78% when treated medically and thus requires a different management, such as a decompressive craniectomy. The main aim of this study is to review this procedure., Development: We conducted a search in the literature published over the last 20 years on this subject. Most of the studies are series of clinical cases with very favourable surgical outcomes. In non-random case-control studies the mortality rate was seen to decrease in the surgical group, and more so if the intervention was carried out early, as compared to the group that underwent medical treatment. Another study that compared decompressive craniectomy with hypothermia showed a higher survival rate in the surgical group. The post-surgery morbidity rate has not been determined, although it seems to be lower in infarction of the non-dominant hemisphere and in younger patients., Conclusions: The low degree of conclusiveness of the studies published to date only enables us to offer one practical opinion concerning this issue: decompressive craniectomy should be evaluated on an individual basis in patients with MMCI who do not respond to medical treatment. The final decision and the most appropriate moment to operate on the patient following the stroke must be based on the family's opinion and on the clinical features of the patient.

The discoidin domain receptor 2 (DDR2) is a member of a subfamily of receptor tyrosine kinases whose ligands are fibrillar collagens, and is widely expressed in postnatal tissues. We have generated DDR2-deficient mice to establish the in vivo functions of this receptor, which have remained obscure. These mice exhibit dwarfism and shortening of long bones. This phenotype appears to be caused by reduced chondrocyte proliferation, rather than aberrant differentiation or function. In a skin wound healing model, DDR2-/- mice exhibit a reduced proliferative response compared with wild-type littermates. In vitro, fibroblasts derived from DDR2-/- mutants proliferate more slowly than wild-type fibroblasts, a defect that is rescued by introduction of wild-type but not kinase-dead DDR2 receptor. Together our results suggest that DDR2 acts as an extracellular matrix sensor to modulate cell proliferation.

Introduction: An inflammatory pseudotumour is a condition of unknown origin and inflammatory nature. It is rarely found in the CNS. We report a case of inflammatory pseudotumour localized to the IV ventricle and review the clinical characteristics of previously reported cases in order to outline the clinical profile of this condition., Clinical Case: A 40 year old man was admitted to hospital complaining of a subacute condition involving difficulty in speaking and in moving his right arm and leg. On examination he had ocular deviation on initial gaze, a complete right Horner's syndrome, right supranuclear facial palsy, dyssynergy-asymmetry on the right finger-nose test and a dissociated sensitivity disorder of the left arm. On MR of the brain there was a space occupying lesion, nodular in form and fixed to the roof of the fourth ventricle. The histopathological report on the specimen removed by surgery stated it to be an inflammatory pseudotumour. On a MEDLINE search for reported cases of inflammatory pseudotumour of the CNS, 27 were found since 1967. Four cases, including ours, involved masses growing into the interior of the fourth ventricle., Conclusions: Inflammatory pseudotumour of the CNS is a condition affecting young adults, with a slight male predominance and some association with clinical and analytical data suggesting autoimmune dysfunction. The intraventricular site, particularly within the fourth ventricle, is relatively common (4/28) and is usually associated with clinical features of dysfunction of the posterior fossa and/or intracranial hypertension. We consider that inflammatory pseudotumour should be included in the differential diagnosis of tumours of the fourth ventricle.

Introduction: The Parry-Romberg syndrome is a clinical condition in which there is progressive facial hemiatrophy which may be associated with neurological, ocular, cutaneous and auto-immune disorders. It is of unknown aetiology, although many theories have been put forward., Clinical Case: We present a case of left facial hemiatrophy associated with ipsilateral lingual hemiatrophy and signs of cortico-cerebellar dysfunction, the neuroimaging findings (NMR) and clinico-radiological follow-up covered a period of over 10 years., Conclusion: The data on the clinical course and neuroimaging, together with our review of the literature, suggest that the Parry-Romberg syndrome may be considered to be a dysgenetic process which may originate during the first stages of CNS embryogenesis.

The acquisition of spatial and functional asymmetry between the rear and the front of the cell is a necessary step for cell chemotaxis. Insulin-like growth factor-I (IGF-I) stimulation of the human adenocarcinoma MCF-7 induces a polarized phenotype characterized by asymmetrical CCR5 chemokine receptor redistribution to the leading cell edge. CCR5 associates with membrane raft microdomains, and its polarization parallels redistribution of raft molecules, including the raft-associated ganglioside GM1, glycosylphosphatidylinositol-anchored green fluorescent protein and ephrinB1, to the leading edge. The non-raft proteins transferrin receptor and a mutant ephrinB1 are distributed homogeneously in migrating MCF-7 cells, supporting the raft localization requirement for polarization. IGF-I stimulation of cholesterol-depleted cells induces projection of multiple pseudopodia over the entire cell periphery, indicating that raft disruption specifically affects the acquisition of cell polarity, but not IGF-I-induced protrusion activity. Cholesterol depletion inhibits MCF-7 chemotaxis, which is restored by replenishing cholesterol. Our results indicate that initial segregation between raft and non-raft membrane proteins mediates the necessary redistribution of specialized molecules for cell migration.

Renal artery embolism is an infrequent entity that occurs in patients with underlying cardiac diseases. Diagnosis is usually difficult unless the index of suspicion is high. Local thrombolysis with low-dose fibrinolytic agents is an useful therapeutic intervention. We present 2 cases of renal artery embolism treated with intra-arterial urokinase and review clinical features and therapeutic options.

Desmoid tumor is a rare neoplasm with extra-abdominal location and female predilection. Anatomopatological analysis is necessary to establish the diagnosis unequivocally, but Magnetic Resonance is the no aggressive method with the best sensitivity and specificity. Surgical resection is the elective treatment yet, and prognosis is not so good as it could be expected in a benign tumor. We report a young male case without polyposis coli antecedents. When he was attended, he related only an abdominal bulk with no other symptom. An intra-abdominal mass 32 cm length per 25 cm width consistent with desmoid tumor was finally resected.

Pulmonary haemorrhage is a severe complication of small-vessel vasculitis associated with antineutrophil cytoplasm antibodies (ANCA). The main pathologic finding is a pauci-immune capillaritis, although occasionally this lesion is not present. The differential diagnosis includes different diseases and therefore ANCA measurement is important. Two cases of pulmonary haemorrhage associated with ANCA in patients with a clinical picture suggesting small-vessel vasculitis is here reported and a review of the literature is made.

Transmembrane ephrinB proteins have important functions during embryonic patterning as ligands for Eph receptor tyrosine kinases and presumably as signal-transducing receptor-like molecules. Consistent with "reverse" signaling, ephrinB1 is localized in sphingo-lipid/cholesterol-enriched raft microdomains, platforms for the localized concentration and activation of signaling molecules. Glutamate receptor-interacting protein (GRIP) and a highly related protein, which we have termed GRIP2, are recruited into these rafts through association with the C-terminal PDZ target site of ephrinB1. Stimulation of ephrinB1 with soluble EphB2 receptor ectodomain causes the formation of large raft patches that also contain GRIP proteins. Moreover, a GRIP-associated serine/threonine kinase activity is recruited into ephrinB1-GRIP complexes. Our findings suggest that GRIP proteins provide a scaffold for the assembly of a multiprotein signaling complex downstream of ephrinB ligands.

The Eph family of receptor protein-tyrosine kinases (RTKs) have recently been implicated in patterning and wiring events in the developing nervous system. Eph receptors are unique among other RTKs in that they fall into two large subclasses that show distinct ligand specificities and for the fact that they themselves might function as 'ligands', thereby activating bidirectional signaling. To gain insight into the mechanisms of ligand-receptor interaction, we have mapped the ligand binding domain in Eph receptors. By using a series of deletion and domain substitution mutants, we now report that an N-terminal globular domain of the Nuk/Cek5 receptor is the ligand binding domain of the transmembrane ligand Lerk2. Using focus formation assays, we show that the Cek5 globular domain is sufficient to confer Lerk2-dependent transforming activity on the Cek9 orphan receptor. Extending our binding studies to other members of both subclasses of receptors, it became apparent that the same domain is used for binding of both transmembrane and glycosylphosphatidyl-anchored ligands. Our studies have determined the first structural elements involved in ligand-receptor interaction and will allow more fine-tuned genetic experiments to elucidate the mechanism of action of these important guidance molecules.

The Eph-related family of receptor tyrosine kinases consists of at least 13 members, several of which display distinctive expression patterns in the developing and adult nervous system. Recently, a small family of ligands, structurally related to the B61 protein, was identified. Binding of these ligands to Eph-related receptors did not, however, elicit measurable biological signals in cultured cells. In order to study functional interactions between B61-related ligands and Eph-related receptors, we constructed chimeric receptors, containing an Eph-related ectodomain and the cytoplasmic domain of the TrkB neurotrophin receptor. Expression and activation of such chimeric receptors in NIH 3T3 cells induced transformation in focus formation assays. Membrane-bound LERK2 ligand is shown to signal through three different Eph-related receptors, namely Cek5, Cek10 and Elk. LERK2, however, fails to interact functionally with the Cek9 receptor. Quantitative analysis including binding assays indicates that Cek10 is the preferred LERK2 receptor. Preliminary mutagenesis of the LERK2 protein suggests a negative regulatory role for its cytoplasmic domain in LERK2 signaling.

A restrospective study was performed on patients presenting with status asthmaticus and admitted to the Intensive Care Unit of the Provincial Clinical and Surgical Teaching hospital, Pinar del Río, within a 5-year period and who underwent mechanical ventilation representing 32.65% of the overall number of admissions in the ICU. Fifty seven percent of the patients were women with an average age of 48 years. The mean intubation time was 60 hours. At admission, the patient's clinical condition was assessed, as well as the cause for intubation and ventilatory parameters that are being used up to date. Complications and the mortality rate which increased to 9.38% were also analyzed. All results were compared to the ones from other authors, as well as from the national and international literature.

Hormone dependence of prostate cancer is well known. In 80% of cases with metastases, hormone suppression leads to the reduction of tumour volume and related disorders. However the treatment is generally palliative because malignant process recurs after about around 16 months. Mean survival is less than 3 years in these forms. Lack of response come always together with a poor prognosis, and there is 90% mortality at 2 years. Advanced prostatic cancer should not be treated with hormones if the patient has few symptoms and his quality of life is satisfactory. Symptomatic forms require hormone manipulation. Orchidectomy or LH-RH are recommended. Total androgen ablation (combined treatment) leads rapidly to more relief of symptoms, but its drawbacks and especially high cost indicate that its use should be weighed individually. Estramustine is not a first-lune treatment. Presently, there is no criteria to predict response to treatment.

Percutaneous endoscopic treatment of the kidney retains a place in the treatment of renal stones (percutaneous nephrolithotomy--PCNL) and ureteropelvic junction abnormalities (endopyeloplasty). It requires anaesthesia ensuring surgical comfort and safety for the patients despite changes in position and the prolonged ventral supine position. The operation carries certain iatrogenic risks related to caliceal irrigation in patients with more or less documented episodes of infection and carries risks of haemorrhage and effraction of adjacent organs. 282 patients treated by PCNL between 1984 and 1991 were reviewed in order to define the respective indications for general anaesthesia and peridural anaesthesia and to determine the modalities, to evaluate the risk and severity of absorption of irrigation fluid and to assess the risk of infection by defining the indications for prophylactic antibiotics. General anaesthesia, using etomidate and propofol via an infusion pump, ensures surgical comfort, anaesthetic safety and better control of intraoperative complications. The renewed interest in this technique must be counterbalanced by the growing incidence of anaphylactic reactions related to anaesthetic drugs. Operations lasting more than 2 hours, raised intracaliceal pressure, the initially exclusive use of glycine for irrigation induce haemodilution complications, possibly aggravated by glycine intoxication. Repeated surgery is preferable with the use of an Amplatz tube as often as possible and physiological saline, except when required by the operation. Patients with a history of urinary tract infection or infected stones should receive prolonged and effective antibiotics before, during and after the operation. Prophylactic antibiotics are reserved for those patients with no history of infection. These principles equally apply to percutaneous nephrolithotomy and endopyeloplasty.

This paper studies all cases affected by 5 parotiditis from January to September 1986 (1767 cases) and 1987 (124 cases), as well as all patients with rubella reported in the same period in 1986 (584 cases) and 1987 (5 cases) in the province of Pinar del Río. The rise in the incidence of the two diseases with an annual basis per 100,000 population during 1986 in the different municipalities is emphasized. The overtly downward trend of these two diseases in 1987 after the administration of the triple viral vaccine--93% for mumps and 99.15% for rubella--is discussed. It was found that these two diseases affected more often school children (5-14 years). It was found that these two diseases are not frequent under the first year of life (76.4 and 120.1 cases per 100,000 population respectively). The percentage of vaccine effectiveness was documented--97.4% for parotiditis and 100% for rubella.