Spatial modules of coherent activity in pathway-specific LFPs in the hippocampus reflect topology and different modes of presynaptic synchronization.

Ongoing network activity often manifests as irregular fluctuations in local field potentials (LFPs), a complex mixture of multicellular synaptic currents of varying locations and extensions. Among other conditions, for synchronously firing presynaptic units to generate sizable postsynaptic LFPs, their axonal territories should overlap. We have taken advantage of anatomical regularity of the rat hippocampus and combined multiple linear recordings and spatial discrimination techniques to separate pathway-specific LFPs with enough spatial resolution to discriminate postsynaptic regions of varying activation, and to investigate their presynaptic origin, chemical nature, and spatial extension. We identified 6 main excitatory and inhibitory LFP generators with different synaptic territories in principal cells and hippocampal subfields matching anatomical pathways. Some recognized pathways did not contribute notably to LFPs. Each showed different septo-temporal spatial modules over which the field potential fluctuations were synchronous. These modules were explained by either the strong overlap of synaptic territories of coactivated afferent neurons (e.g., CA3 clusters for CA1 Schaffer LFPs), or widespread coalescence of postsynaptic territories (granule cell somatic inhibition). We also show evidence that distinct modes of afferent synchronization generate stereotyped spatial patterns of synchronous LFPs in one pathway. Thus, studying spatial coherence of pathway-specific LFPs provides remote access to the dynamics of afferent populations.

Presumed fluoxetine maculopathy.

To report a unique case of a patient who developed simultaneous bilateral maculopathy presumed from intake of fluoxetine. The optic coherence tomography (OCT) macular showed a subfoveal disruption in the outer retinal layer in both eyes (OU), higher in the left one (OS). Although reported cases of serotonin recapture inhibitors (SSRIs) Maculopathy so far have been caused by sertraline, fluoxetine shares the biological mechanism, and OCT findings and ocular symptoms are the same as published. We should be aware with ocular symptoms in patients that take fluoxetine.

Risk factors and clinical impact of multidrug resistance in healthcare-associated bacteraemic urinary tract infections: a post-hoc analysis of a multicentre prospective cohort in Spain.

BACKGROUND: The global burden associated with antimicrobial resistance is of increasing concern. AIM: To evaluate risk factors associated with multidrug-resistant (MDR) infection and its clinical impact in a cohort of patients with healthcare-associated bacteraemic urinary tract infections (BUTIs). METHODS: This was a prospective, multicentre, post-hoc analysis of patients with healthcare-associated-BUTI (ITUBRAS-2). The primary outcome was MDR profile. Secondary outcomes were clinical response (at 48-72 h and at hospital discharge) and length of hospital stay from onset of BUTI. Logistic regression was used to evaluate variables associated with MDR profile and clinical response. Length of hospital stay was evaluated using multivariate median regression. FINDINGS: In all, 443 episodes were included, of which 271 (61.17%) were classified as expressing an MDR profile. In univariate analysis, MDR profile was associated with E. coli episodes (odds ratio (OR): 3.13; 95% confidence interval (CI): 2.11-4.69, P < 0.001) and the extensively drug-resistant (XDR) pattern with P. aeruginosa aetiology (7.84; 2.37-25.95; P = 0.001). MDR was independently associated with prior use of fluoroquinolones (adjusted OR: 2.43; 95% CI: 1.25-4.69), cephalosporins (2.14; 1.35-3.41), and imipenem or meropenem (2.08; 1.03-4.20) but not with prior ertapenem. In terms of outcomes, MDR profile was not associated with lower frequency of clinical cure, but was associated with longer hospital stay. CONCLUSION: MDR profile was independently associated with prior use of fluoroquinolones, cephalosporins, imipenem, and meropenem, but not with prior ertapenem. MDR-BUTI episodes were not associated with worse clinical cure, although they were independently associated with longer duration of hospital stay.

Predictive factors for early mortality among patients with methicillin-resistant Staphylococcus aureus bacteraemia.

OBJECTIVES: A high proportion of patients with methicillin-resistant Staphylococcus aureus (MRSA) bacteraemia die within a few days of the onset of infection. However, predictive factors for early mortality (EM) have barely been examined. The aim of this study was to determine the predictive factors for EM in patients with MRSA bacteraemia. METHODS: All episodes of MRSA bacteraemia were prospectively followed in 21 Spanish hospitals from June 2008 to December 2009. Epidemiology, clinical data, therapy and outcome were recorded. All MRSA strains were analysed in a central laboratory. Mortality was defined as death from any cause occurring in the 30 days after the onset of MRSA bacteraemia. EM was defined as patients who died within the first 2 days, and late mortality (LM) for patients who died after this period. Multivariate analyses were performed by using logistic regression models. RESULTS: A total of 579 episodes were recorded. Mortality was observed in 179 patients (31%): it was early in 49 (8.5%) patients and late in 130 (22.5%). Independent risk factors for EM were [OR (95% CI)] initial Pitt score >3 [3.99 (1.72-3.24)], previous rapid fatal disease [3.67 (1.32-10.24)], source of infection lower respiratory tract or unknown [3.76 (1.31-10.83) and 2.83 (1.11-7.21)], non-nosocomial acquisition [2.59 (1.16-5.77)] and inappropriate initial antibiotic therapy [3.59 (1.63-7.89)]. When predictive factors for EM and LM were compared, inappropriate initial antibiotic therapy was the only distinctive predictor of EM, while endocarditis and lower respiratory tract sources both predicted LM. CONCLUSIONS: In our large cohort of patients several factors were related to EM, but the only distinctive predictor of EM was inappropriate initial antibiotic therapy.

Incidence, associated disease burden and healthcare utilization due to Staphylococcus aureus prosthetic joint infection in European hospitals: the COMBACTE-NET ARTHR-IS multi-centre study.

BACKGROUND: The aim of this study was to estimate the incidence, associated disease burden and healthcare utilization due to Staphylococcus aureus prosthetic joint infections (SA-PJI) after primary hip and knee arthroplasty in European centres. METHODS: This study was conducted in patients who underwent primary hip and knee arthroplasty in 19 European hospitals between 2014 and 2016. The global incidence of PJI and SA-PJI was calculated. The associated disease burden was measured indirectly as infection-related mortality plus loss of function. For healthcare utilization, number and duration of hospitalizations, number and type of surgical procedures, duration of antibiotic treatments, and number of outpatient visits were collected. Subgroup and regression analyses were used to evaluate the impact of SA-PJI on healthcare utilization, controlling for confounding variables. RESULTS: The incidence of PJI caused by any micro-organism was 1.41%, and 0.40% for SA-PJI. Among SA-PJI, 20.7% were due to MRSA with substantial regional differences, and were more frequent in partial hip arthroplasty (PHA). Related deaths and loss of function occurred in 7.0% and 10.2% of SA-PJI cases, respectively, and were higher in patients with PHA. Compared with patients without PJI, patients with SA-PJI had a mean of 1.4 more readmissions, 25.1 more days of hospitalization, underwent 1.8 more surgical procedures, and had 5.4 more outpatient visits, controlling for confounding variables. Healthcare utilization was higher in patients who failed surgical treatment of SA-PJI. CONCLUSIONS: This study confirmed that the SA-PJI burden is high, especially in PHA, and provided a solid basis for planning interventions to prevent SA-PJI.

Pulmonary infections in HIV-infected patients: an update in the 21st century.

From the first descriptions of HIV/AIDS, the lung has been the site most frequently affected by the disease. Most patients develop a pulmonary complication during the history of HIV infection, mainly of infectious aetiology. Important changes in the epidemiology of HIV-related pulmonary infections have occurred. Overall, prescription of Pneumocystis jirovecii prophylaxis and the introduction of highly active antiretroviral therapy (HAART) are the main causes. Currently, the most frequent diagnosis in developed countries is bacterial pneumonia, especially pneumococcal pneumonia, the second most frequent cause is Pneumocystis pneumonia and the third is tuberculosis. However, in Africa, tuberculosis could be the most common pulmonary complication of HIV. Pulmonary infections remain one of the most important causes of morbidity and mortality in these patients, and the first cause of hospital admission in the HAART era. Achieving an aetiological diagnosis of pulmonary infection in these patients is important due to its prognostic consequences.

High prevalence of upper urinary tract involvement detected by 111indium-oxine leukocyte scintigraphy in patients with candiduria.

The purpose of this investigation was to assess the prevalence of upper urinary tract involvement in patients with candiduria by means of (111)indium-oxine-labeled leukocyte scintigraphy. An observational cohort study of patients with confirmed candiduria was conducted in an acute-care teaching hospital in Spain from March 2006 through February 2009. An (111)In-labeled leukocyte scan was performed in order to assess the upper urinary tract involvement. A series of non-matched patients without candiduria nor bacteriuria undergoing scintigraphy to exclude infections in other sites than the urinary tract was also studied. Demographics, baseline illness, and clinical data were recorded. Candiduria was detected in 428 patients, and scintigraphy was performed in 35 of these patients. Twenty-nine patients without candiduria nor bacteriuria were also studied. Positive renal scintigraphy was documented in 24 (68%) patients with confirmed candiduria and in 3 (10%) patients without candiduria (p < 0.005). Renal uptake was not associated with a higher mortality nor with re-admissions. Subclinical pyelonephritis could be more frequent in patients with candiduria than it has been previously considered.

[Value of the direct cystoscintigraphy in the diagnosis of vesicoureteral reflux in patients with prenatal hydronephrosis]. / Valor de la cistogammagrafía directa en el diagnóstico del reflujo vesicoureteral en pacientes con hidronefrosis prenatal.

OBJECTIVE: As the radiation received in conventional cystography is about 20 times higher than radionuclide cystography and the sensitivity of the last is higher in order to diagnose vesicoureteral reflux, we consider the use of radionuclide cystography in early detection of reflux in patients with prenatally detected hydronephrosis. MATERIALS AND METHODS: Between 2003 and 2009, a study of neonates with prenatal history of hydronephrosis was performed in order to rule out reflux. Our protocol was as follows: The diagnosis was confirmed by postnatal ultrasound at 1 week (in this case patient initiate antibiotic prophylaxis). A new ultrasound was repeated at 6 weeks, if the dilatation was larger than 8 mm at this time, direct radionuclide scintigraphy was performed. The patients were placed on prophylactic antibiotics until the screenining results were known. Conventional cystography was performed if a male infant showed severe dilatation, or in general in cases with parenchymatous atrophy or if a duplex system was suspected. RESULTS: In 13 (20%) of the 65 cases (18 kidneys) reflux was detected (3 minor, 8 moderate and 7 severe). In most cases, follow up was performed with radionuclide cystography. None of the patients with reflux placed on prophylactic antibiotics developed a febrile urinary tract infection during the first year of life. CONCLUSIONS: Direct radionuclide cystography is a useful diagnostic method in early detection of vesicoureteral reflux in patients with prenatal hydronephrosis with higher sensitivity than conventional cystography, and with an important advantage concerning radiation of the patient. Patients screened and placed on prophylactic antibiotics are probably going to present less episodes of pielonephrytis.

Minor contribution of principal excitatory pathways to hippocampal LFPs in the anesthetized rat: a combined independent component and current source density study.

Analysis of local field potentials (LFPs) helps understand the function of the converging neuronal populations that produce the mixed synaptic activity in principal cells. Recently, using independent component analysis (ICA), we resolved ongoing hippocampal activity into several major contributions of stratified LFP-generators. Here, using pathway-specific LFP reconstruction, we isolated LFP-generators that describe the activity of Schaffer-CA1 and Perforant-Dentate excitatory inputs in the anesthetized rat. First, we applied ICA and current source density analysis to LFPs evoked by electrical subthreshold stimulation of the pathways. The results showed that pathway specific activity is selectively captured by individual components or LFP-generators. Each generator matches the known distribution of axonal terminal fields in the hippocampus and recovers the specific time course of their activation. Second, we use sparse weak electrical stimulation to prime ongoing LFPs with activity of a known origin. Decomposition of ongoing LFPs yields a few significant LFP-generators with distinct spatiotemporal characteristics for the Schaffer and Perforant inputs. Both pathways convey an irregular temporal pattern in bouts of population activity of varying amplitude. Importantly, the contribution of Schaffer and Perforant inputs to the power of raw LFPs in the hippocampus is minor (7 and 5%, respectively). The results support the hypothesis on a sparse population code used by excitatory populations in the entorhino-hippocampal system, and they validate the separation of LFP-generators as a powerful tool to explore the computational function of neuronal circuits in real time.

Suppressive antibiotic therapy in prosthetic joint infections: a multicentre cohort study.

OBJECTIVES: The aim was to describe the effectiveness of suppressive antibiotic treatment (SAT) in routine clinical practice when used in situations in which removal of a prosthetic implant is considered essential for the eradication of an infection, and it cannot be performed. METHODS: This was a descriptive retrospective and multicentre cohort study of prosthetic joint infection (PJI) cases managed with SAT. SAT was considered to have failed if a fistula appeared or persisted, if debridement was necessary, if the prosthesis was removed due to persistence of the infection or if uncontrolled symptoms were present. RESULTS: In total, 302 patients were analysed. Two hundred and three of these patients (67.2%) received monotherapy. The most commonly used drugs were tetracyclines (39.7% of patients) (120/302) and cotrimoxazole (35.4% of patients) (107/302). SAT was considered successful in 58.6% (177/302) of the patients (median time administered, 36.5 months; IQR 20.75-59.25). Infection was controlled in 50% of patients at 5 years according to Kaplan-Meier analysis. Resistance development was documented in 15 of 65 (23.1%) of the microbiologically documented cases. SAT failure was associated with age <70 years (sub-hazard ratio (SHR) 1.61, 95% CI 1.1-2.33), aetiology other than Gram-positive cocci (SHR 1.56, 95% CI 1.09-2.27) and location of the prosthesis in the upper limb (SHR 2.4, 95% CI 1.5-3.84). SAT suspension was necessary due to adverse effects in 17 of 302 patients (5.6%). CONCLUSIONS: SAT offers acceptable results for patients with PJI when surgical treatment is not performed or when it fails to eradicate the infection.

Time trends in the aetiology of prosthetic joint infections: a multicentre cohort study.

It is important to know the spectrum of the microbial aetiology of prosthetic joint infections (PJIs) to guide empiric treatment and establish antimicrobial prophylaxis in joint replacements. There are no available data based on large contemporary patient cohorts. We sought to characterize the causative pathogens of PJIs and to evaluate trends in the microbial aetiology. We hypothesized that the frequency of antimicrobial-resistant organisms in PJIs has increased in the recent years. We performed a cohort study in 19 hospitals in Spain, from 2003 to 2012. For each 2-year period (2003-2004 to 2011-2012), the incidence of microorganisms causing PJIs and multidrug-resistant bacteria was assessed. Temporal trends over the study period were evaluated. We included 2524 consecutive adult patients with a diagnosis of PJI. A microbiological diagnosis was obtained for 2288 cases (90.6%). Staphylococci were the most common cause of infection (1492, 65.2%). However, a statistically significant rising linear trend was observed for the proportion of infections caused by Gram-negative bacilli, mainly due to the increase in the last 2-year period (25% in 2003-2004, 33.3% in 2011-2012; p 0.024 for trend). No particular species contributed disproportionally to this overall increase. The percentage of multidrug-resistant bacteria PJIs increased from 9.3% in 2003-2004 to 15.8% in 2011-2012 (p 0.008), mainly because of the significant rise in multidrug-resistant Gram-negative bacilli (from 5.3% in 2003-2004 to 8.2% in 2011-2012; p 0.032). The observed trends have important implications for the management of PJIs and prophylaxis in joint replacements.

Invasive pulmonary aspergillosis in solid organ and bone marrow transplant recipients.

BACKGROUND: Invasive pulmonary aspergillosis (IPA) remains a major cause of mortality in transplant recipients. New strategies in therapy are needed. METHODS: We prospectively followed all solid organ and bone marrow transplant recipients from January 1998 to January 2003 who showed pulmonary infiltrates. We retrospectively analyzed all of the patients diagnosed as having IPA. Clinical and epidemiological data were collected. Influence of new treatment strategies on survival was also analyzed. RESULTS: Thirty-one cases of API were found: 8 definite, 18 probable, 5 possible among recipients of liver (11), bone marrow (9), kidney (7), kidney-pancreas (3), and heart (1) transplants. Five patients (16%) were previously receiving antifungal prophylaxis. The most common symptoms were fever (74%) and dyspnea and dry cough (48%). Six cases (19%) showed dissemination to extrapulmonary sites: central nervous system (CNS) in five and bone in one. The most common radiographic patterns were alveolar infiltrates (58%); the lesions were usually diffuse and bilateral (58%). The most common Aspergillus species identified was A. fumigatus (74%). The test to detect Aspergillus antigen (galactomannan) in serum performed in 13 cases, was positive in eight (61%). The crude mortality rate was 61% (19 of 31), but in patients on mechanical ventilation, it was 94% (OR 88, IC 95%: 7.1-1094), and in patients with CNS involvement, it was 100%. The influence of the different treatment regimens on survival was analyzed in definite and probable cases: Group 1 (12) included patients who received conventional monotherapy and group 2 (12) patients received combination antifungal therapy or liposomal amphotericin B (1-AMB) at high doses. The mortality in group 1 was 83% (10 of 12), and in group 2 it was 42% (5 of 12) (P < 0.05). CONCLUSIONS: The mortality rate of IPA remains high, especially among patients with CNS involvement or those under mechanical ventilation. Combined antifungal therapy or monotherapy with 1-AMB at high doses significantly reduced mortality compared with conventional monotherapy.

Bone marrow biopsy in the diagnosis of fever of unknown origin in patients with acquired immunodeficiency syndrome.

BACKGROUND: Fever is commonly observed in patients with human immunodeficiency virus (HIV) disease and frequently eludes diagnosis. The role of bone marrow biopsy in the diagnosis of fever of unknown origin in patients infected with HIV remains controversial. PATIENTS AND METHODS: One hundred twenty-three consecutive patients with 137 episodes of fever lasting 10 or more days without diagnosis after 1 week of hospitalization were evaluated by bone marrow biopsy. RESULTS: Overall, a specific diagnosis was achieved in 52 episodes by means of culture and histopathological examination (diagnostic yield, 37.9%). Three types of disease were found: mycobacterial infections (n = 36, 69% of documented episodes), including 18 patients with disseminated tuberculosis and 14 with Mycobacterium avium-intracellulare complex infections; non-Hodgkin lymphomas (n = 12, 23%); and visceral leishmaniasis (n = 4, 8%). Although bone marrow cultures were more sensitive than microscopic examination with special stains for the diagnosis of mycobacterial infections, the pathological examination of bone marrow led to a more rapid diagnosis of disease. In addition, the histopathological examination of bone marrow alone led to the diagnosis of a specific condition in 43 episodes (31.3% of all episodes). CONCLUSIONS: Bone marrow biopsy is a useful procedure for the diagnosis of fever in patients with advanced HIV disease, particularly in areas where tuberculosis and leishmaniasis are prevalent. Involvement of the marrow may be the first indication of the existence of extranodal non-Hodgkin lymphoma. For Mycobacterium avium-intracellulare complex infection, blood cultures were more sensitive than bone marrow biopsy.

[Validation of a respiratory polygraphy system in the diagnosis of sleep apnea syndrome]. / Validación de un equipo de poligrafía respiratoria en el diagnóstico del síndrome de apneas durante el sueño.

OBJECTIVE: To validate a cardiorespiratory polygraphy system (BITMED NGP 140) by comparing it to conventional polysomnography in the diagnosis of sleep apnea-hypopnea syndrome. PATIENTS AND METHODS: Polysomnography and cardio-respiratory polygraphy were performed simultaneously on 103 consecutive patients referred because of suspected sleep apnea-hypopnea syndrome. The Bland and Altman method and intraclass correlation coefficients were used to assess agreement between the 2 methods of measurement. Receiver operating characteristic (ROC) curves were used to calculate the yield of cardiorespiratory polygraphy compared to that of conventional polysomnography. RESULTS: Ninety-two valid studies were obtained for 72 men and 20 women (mean [SD] age: 52.4 [12] years). By the Bland and Altman method, the difference between the respiratory event index obtained with the BITMED NGP140 and the apnea-hypopnea index (AHI) obtained by conventional polysomnography was 7.6 (13.2) in the manual analysis (95% confidence interval [CI], 4.9-10.4) and 12 (15.3) (95% CI, 8.8-15.3) in the automatic analysis. For a corrected AHI (AH/total time in bed) mean differences were -2.2 (5.9) and 2.4 (8.2) for manual and automatic analysis. The intraclass correlation coefficients were greater than 0.94. The areas under the ROC curves of the respiratory event index were greater than 0.97 for all cut points. For an AHI of 30 or higher, the best cut-off point determined by manual cardiorespiratory polygraphy analysis was 27 (sensitivity, 98% and specificity, 98%). For the different cut-off points cardiorespiratory polygraphy correctly classified between 92% and 98% of patients in both the manual and automatic analyses. CONCLUSIONS: The BITMED NGP140 had good agreement with conventional polysomnography for the measurement of respiratory events and provided high diagnostic yield.

Differential spatiotemporal expression of E- and P-cadherin during mouse tooth development.

Changes in E- and P-cadherin (E- and P-CD) expression during embryonic mouse first molar development were analyzed by immunohistochemistry. During the induction and morphogenesis stages (bud, cap and early bell stages), E-CD was expressed in the cells of the invaginating epithelial tooth bud and in the cells of the outer enamel epithelium, stellate reticulum and stratum intermedium, suggesting a role for this molecule in the maintenance of enamel organ architecture. On the other hand, P-CD was strongly expressed in the inner enamel epithelium suggesting its participation in the processes of mesenchymal induction. during the cytodifferentiation stage (late bell stage), E-CD was expressed in polarizing preameloblasts, but cadherin expression was restricted to the basal and apical poles of differentiated secretory ameloblasts, where the zonula adherens type of cell-cell junctions is located. The present study demonstrates for the first time the spatiotemporal expression of cadherins during tooth development and suggests differential and specific roles for E-CD and P-CD during the morphogenesis and cytodifferentiation processes of this organ.

Clinical features and outcomes of tuberculosis in transplant recipients as compared with the general population: a retrospective matched cohort study.

There are no previous studies comparing tuberculosis in transplant recipients (TRs) with other hosts. We compared the characteristics and outcomes of tuberculosis in TRs and patients from the general population. Twenty-two TRs who developed tuberculosis from 1996 through 2010 at a tertiary hospital were included. Each TR was matched by age, gender and year of diagnosis with four controls selected from among non-TR non-human immunodeficiency virus patients with tuberculosis. TRs (21 patients, 96%) had more factors predisposing to tuberculosis than non-TRs (33, 38%) (p <0.001). Pulmonary tuberculosis was more common in non-TRs (77 (88%) vs. 12 TRs (55%); p 0.001); disseminated tuberculosis was more frequent in TRs (five (23%) vs. four non-TRs (5%); p 0.005). Time from clinical suspicion of tuberculosis to definitive diagnosis was longer in TRs (median of 14 days) than in non-TRs (median of 0 days) (p <0.001), and invasive procedures were more often required (12 (55%) TRs and 15 (17%) non-TRs, respectively; p 0.001). Tuberculosis was diagnosed post-mortem in three TRs (14%) and in no non-TRs (p <0.001). Rates of toxicity associated with antituberculous therapy were 38% in TRs (six patients) and 10% (seven patients) in non-TRs (p 0.014). Tuberculosis-related mortality rates in TRs and non-TRs were 18% and 6%, respectively (p 0.057). The adjusted Cox regression analysis showed that the only predictor of tuberculosis-related mortality was a higher number of organs with tuberculosis involvement (adjusted hazard ratio 8.6; 95% CI 1.2-63). In conclusion, manifestations of tuberculosis in TRs differ from those in normal hosts. Post-transplant tuberculosis resists timely diagnosis, and is associated with a higher risk of death before a diagnosis can be made.

Native valve endocarditis due to Candida glabrata treated without valvular replacement: a potential role for caspofungin in the induction and maintenance treatment.

Conventional antifungal therapy for fungal endocarditis has been associated with a poor cure rate. Therefore, combined medical and surgical therapy has been recommended. However, new potent antifungal agents, such as echinocandins, could increase the medical options and, in some cases, avoid the need for surgery. We report a case of Candida endocarditis treated successfully without valve replacement with intravenous liposomal amphotericin B (total dose, 4 g) and intravenous caspofungin (a 100-mg loading dose followed by 50 mg per day for 8 weeks) as induction therapy and intravenous caspofungin (100 mg 3 times per week for 12 weeks) as maintenance therapy.

Alternariosis after liver transplantation.

Alternaria is a saprophytic fungus that is increasingly recognized as a human pathogen, particularly in immunocompromised hosts, including solid-organ transplant recipients. Although combined surgical and medical treatment seem to be useful in the management of this infection, an optimal antifungal therapy remains to be defined. Only four cases of alternariosis after orthotopic liver transplantation have been reported. We describe an additional case and review the literature on infections due to Alternaria in organ transplant recipients, with special emphasis on treatment.

Expression of E-cadherin in 230 infiltrating ductal breast carcinoma.

The immunohistochemical expression of E-cadherin (E-CD) was correlated to differentiation grade, tumor size, axillary lymph node metastasis, hormone receptor status and disease outcome in 230 infiltrating ductal breast carcinomas. E-CD expression was reduced in 116 tumors (50.4%). Reduced E-CD expression was more frequently found in high histological grade and progesterone receptor negative tumors. In contrast, preserved E-CD expression was more frequently observed in tumors with axillary lymph node metastasis, particularly in the group of patients with 1 to 3 positive lymph nodes. A weak association between reduced E-CD expression and shortened overall survival was found in univariate survival analysis, that was lost when the patients were adjusted for other pathological factors in multivariate analysis. These data indicate that E-CD may be considered a differentiation marker in ductal carcinomas of non special type. However, the relationship between E-CD expression and lymph node metastasis and disease outcome remains to be established.

Relationship between ERBB2 and E-cadherin expression in human breast cancer.

A recent in vitro study has suggested that overexpression of ERBB2 may mediate breast tumour progression and metastasis by inhibiting the transcription of the E-cadherin (E-CD) gene. To test this hypothesis in human breast cancer in vivo, we studied the relationship between the expression of both molecules in 247 breast carcinomas immunohistochemically. Five ductal carcinomas in situ overexpressed ERBB2 and showed preserved E-CD expression. Forty-four of 226 infiltrating ductal carcinomas (19.47%) showed ERBB2 overexpression, and a statistically significant relationship was found between ERBB2 overexpression and high histological grade. E-CD expression was preserved in 111 cases (49.1%) and correlated with the histological grade. However, no significant relationship was found between ERBB2 and E-CD expression. None of the 16 infiltrating lobular carcinomas expressed ERBB2 or E-CD. These observations in different histological types of breast carcinoma strongly argue against a role for ERBB2 as a transcriptional regulator of E-CD expression in most human breast carcinomas in vivo.