A contemporary review of Clostridioides difficile infections in patients with haematologic diseases.

Clostridioides (Clostridium) difficile (C. difficile) infection is one of the most common causes of increased morbidity and mortality. Approximately 500 000 C. difficile infections (CDIs) occur each year in the United States, and they result in more than 29 000 deaths. Patients with haematologic diseases are at a higher risk for this infection due to frequent hospitalization and exposure to treatment-associated risk factors. Whilst several currently available antimicrobial agents offer resolution, recurrence of infection remains a major concern. Recent advancement in deciphering C. difficile virulence mechanisms and identification of its allies in contributing to the infection has led to the development of alternative treatment strategies. Here, we will provide a contemporary discussion of how major risk factors in haematologic diseases, such as immunosuppression, chemoradiation, use of antibiotic, proton pump inhibitor and opioid, and deficiency in butyrate and antimicrobial peptides contribute to C. difficile infection. Next, we will highlight different approaches to control and mitigate this infection such as antibiotic stewardship and faecal microbiota transplantation. Finally, we will explore several emerging treatments such as use of pre- and probiotics, immunotherapy and microbiome-sparing agents.

Anastomotic leak after transanal total mesorectal excision: grading of severity and management aimed at preservation of the anastomosis.

AIM: The transanal approach to total mesorectal excision (TaTME) as an alternative to conventional anterior resection offers an improved view to otherwise restricted anatomical regions in obese and narrow male pelves and unfavourable tumour locations. Guidelines for the management of anastomotic leakage (AL) following low rectal resections are scarce. PATIENTS AND METHODS: Prospectively collected data of all consecutive patients undergoing TaTME between December 2014 and April 2017 in our centre were analysed retrospectively. Existing classification systems for AL were modified with regard to transanal anastomotic-preserving management. RESULTS: TaTME was performed in 66 patients with a median age of 56.2 years. The overall incidence of AL was 12.1% (n = 8). AL grading was differentiated in Grades I to V according to the severity of necrosis and abscess development. Two patients suffered from AL Grade II, one patient from Grade III, three patients from Grade IV and two patients from Grade V. Preservation of the anastomosis following AL was achieved by the damage control concept in six of eight patients (75%) with a median duration of hospital stay of 36 days. Two patients received a Hartmann procedure (Grades IV and V). CONCLUSION: Our study demonstrates that management of AL following TaTME is challenging but definitely amenable to strategies aimed at preserving the anastomosis by appropriate damage control. The modified classification system might serve as guidance for anastomosis-preserving management.

Pseudo-Leptomeningeal Contrast Enhancement at 3T in Pediatric Patients Sedated by Propofol.

BACKGROUND AND PURPOSE: Propofol is a cerebral vasoconstrictor that modulates cerebral perfusion by decreasing the metabolic rate of oxygen. Because younger children often undergo intravenous sedation for MR imaging, this study set out to evaluate the degree of leptomeningeal contrast enhancement on 3T postcontrast brain MR imaging and to determine whether this phenomenon relates to sequence, sedation dosage, or patient age or weight. MATERIALS AND METHODS: During a 2-year period, of 152 children 1-5 years of age who underwent MR imaging, 43 were included for MRI review. Of these, 37 underwent postcontrast imaging with either solely gradient-echo T1WI (n = 20) or spin-echo T1WI (n = 17); notably, 6 patients underwent both sequences. Three neuroradiologists separately graded the degree of leptomeningeal contrast enhancement (grades 0-3) that was correlated with various factors and calculated the interobserver reliability. RESULTS: For the 43 patients, the mean patient age was 3.1 ± 1.4 years. The leptomeningeal contrast-enhancement grade was significantly greater (P < .0001) on spin-echo T1WI (1.9-2.1) versus gradient-echo TIWI (1.2-1.4). Patient weight (r = -0.366 to -.418, P = .003-.01) and age (r = -0.315 to -0.418, P = .004-.032) moderately and inversely correlated with the leptomeningeal contrast-enhancement grade, while the propofol dosage, sedation duration, and time to T1WI post-contrast administration did not (each, P > .05). The interobserver κ was strong regarding the leptomeningeal contrast-enhancement grade on both spin-echo T1WI (κ = 0.609-0.693, P < .0001) and gradient-echo TIWI (κ = 0.567-0.698, P < .0001). CONCLUSIONS: Leptomeningeal contrast enhancement (or "pseudo"-leptomeningeal contrast enhancement) occurs with a greater frequency and degree on 3T postcontrast spin-echo T1WI relative to gradient-echo TIWI in younger children sedated with propofol and should not be mistaken for disease. This phenomenon may be more prominent with lower age or size and may arise from propofol-induced vascular smooth-muscle dilation.

Three months of weekly rifapentine plus isoniazid for latent tuberculosis treatment in solid organ transplant candidates.

BACKGROUND: Isoniazid daily for 9 months is the recommended regimen for latent tuberculosis infection (LTBI) in solid organ transplant (SOT) candidates, but its use is controversial, due to reports of hepatotoxicity and low treatment completion rates. A 12-week course of once weekly directly observed therapy (DOT) with isoniazid plus rifapentine (3HP) is a new LTBI treatment regimen. Tolerability and safety data of 3HP LTBI treatment in SOT candidates are limited. METHODS: Twelve consecutive SOT candidates who underwent DOT with 3HP for LTBI at Westchester Medical Center, Valhalla, New York, USA, between January 2013 and August 2016 were prospectively evaluated for tolerability and safety of 3HP. The diagnosis of LTBI was made in a person with a positive interferon-gamma release test, without a history of previously treated active or latent tuberculosis infection, and without signs, symptoms, or radiographic evidence of active tuberculosis. Patients were followed up 1 month after treatment completion and at routine follow-up visits with their transplant providers. RESULTS: Eleven patients were men, and the median age was 60 years (range 44-72). Eight patients were liver, and four kidney transplant candidates. The median Model for End-Stage Liver Disease (MELD score) was 17 (range 10-31). All patients completed treatment. Only a single patient developed transaminitis greater than twice the baseline value. Three patients underwent liver transplantation. None of them developed tuberculosis at 9, 22, or 40 months following transplantation. CONCLUSION: Directly observed 3HP LTBI treatment was not associated with hepatotoxicity, even in patients with higher MELD scores. Further studies are needed to confirm the safety and efficacy of this LTBI treatment regimen in the SOT population.

Late-onset cytomegalovirus infection complicated by Guillain-Barre syndrome in a kidney transplant recipient: case report and review of the literature.

Cytomegalovirus (CMV) infection remains a common infection after solid-organ transplantation. In the general population CMV disease is associated with Guillain-Barre syndrome (GBS), an autoimmune disease leading to an acute peripheral neuropathy, in 1 of 1000 cases. Interestingly, GBS is a rarely observed complication in solid-organ transplant recipients, possibly related to maintenance immunosuppression. We describe a case of CMV infection complicated by GBS in a kidney transplant recipient and review the literature.

ß-Blockers have differential effects on the murine asthma phenotype.

BACKGROUND AND PURPOSE: Our previous studies have shown the ß2 -adrenoceptor and its endogenous ligand, adrenaline, are required for development of the asthma phenotype in murine asthma models. Chronic administration of some, but not other, ß-blockers attenuated the asthma phenotype and led us to hypothesize that biased signalling was the basis of their differential effects, experimentally and clinically. EXPERIMENTAL APPROACH: We used mice with no detectable systemic adrenaline (PNMT(-/-) ) and wild-type (WT) mice to study the effects of four ß-blockers, alprenolol, carvedilol, propranolol and nadolol, in an ovalbumin sensitization and challenge (Ova S/C) murine model of asthma. The parameters measured were inflammatory cell infiltration, mucous metaplasia and airway hyperresponsiveness. To interpret the pharmacological action of these ligands quantitatively, we conducted computer simulations of three-state models of receptor activation. KEY RESULTS: Ova S/C PNMT(-/-) mice do not develop an asthma phenotype. Here, we showed that administration of alprenolol, carvedilol or propranolol in the absence of interference from adrenaline using Ova S/C PNMT(-/-) mice resulted in the development of an asthma phenotype, whereas nadolol had no effect. Ova S/C WT mice did develop an asthma phenotype, and administration of alprenolol, propranolol and carvedilol had no effect on the asthma phenotype. However, nadolol prevented development of the asthma phenotype in Ova S/C WT mice. Computer simulations of these four ligands were consistent with the isolated three-state receptor model. CONCLUSION AND IMPLICATIONS: ß-Blockers have different effects on the murine asthma phenotype that correlate with reported differences in activation or inhibition of downstream ß2 -adrenoceptor signalling pathways.

MRSA and VRE colonization in solid organ transplantation: a meta-analysis of published studies.

The burden of methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant enterococcus (VRE) colonization among the increasing number of solid organ transplant patients has not been systematically explored. We searched PubMed and EMBASE for pertinent articles, performed a meta-analysis of prevalence across eligible studies and estimated the risk of ensuing MRSA or VRE infections relative to colonization status. We stratified effects in the pretransplant and posttransplant period. Twenty-three studies were considered eligible. Seventeen out of 23 (74%) referred to liver transplants. Before transplantation, the pooled prevalence estimate for MRSA and VRE was 8.5% (95% confidence interval [CI] 3.2­15.8) and 11.9% (95% CI 6.8­18.2), respectively. MRSA estimate was influenced by small studies and was lower (4.0%; 95% CI 0.4­10.2) across large studies (>200 patients). After transplantation, the prevalence estimates were 9.4% (95% CI 3.0­18.5) for MRSA and 16.2% (95% CI 10.7­22.6) for VRE. Pretransplant as well as posttransplant MRSA colonization significantly increased the risk for MRSA infections (pooled risk ratio [RR] 5.51; 95% CI 2.36­12.90 and RR 10.56; 95% CI 5.58­19.95, respectively). Pretransplant and posttransplant VRE colonization were also associated with significant risk of VRE infection (RR 6.65; 95% CI 2.54­17.41 and RR 7.93; 95% CI 2.36­26.67, respectively). Solid organ transplantation is a high-risk setting for MRSA and VRE colonization, and carrier state is associated with infection. Upgraded focus in prevention and eradication strategies is warranted.

Update on nontuberculous mycobacterial infections in solid organ and hematopoietic stem cell transplant recipients.

Nontuberculous mycobacteria (NTM) are recognized as emerging pathogens. NTM disease in transplant recipients remains a diagnostic and therapeutic challenge. Herein, a review of the most recent literature will provide an update in regard to the epidemiology, clinical presentation, diagnosis, treatment, and prevention of NTM disease in solid organ and hematopoietic stem cell transplant recipients. Special consideration will be given to the lung transplant population.

Infections following facial composite tissue allotransplantation--single center experience and review of the literature.

We reviewed medical records of all patients (n = 4) who underwent facial composite tissue allotransplantation (FCTA) at our center between April 2009 and May 2011; data were censored in June 2012. We searched for FCTA publications and reviewed them for infectious complications and prophylaxis strategies. Three patients received full and one partial FCTA at our institution. Two recipients were cytomegalovirus (CMV) Donor (D)+/Recipient (R)- and two CMV D+/R+. Perioperative prophylaxis included vancomycin, cefazolin and micafungin and was adjusted based on peritransplant cultures. Additional prophylaxis included trimethoprim-sulfamethoxazole and valganciclovir. Two recipients developed surgical site infection and two developed pneumonia early after transplantation. Both CMV D+/R- recipients developed CMV disease after discontinuation of prophylaxis, recovered with valganciclovir treatment and did not experience subsequent rejection. Other posttransplant infections included bacterial parotitis, polymicrobial bacteremia, invasive dermatophyte infection and Clostridium difficile-associated diarrhea. Nine publications described infectious complications in another 9 FCTA recipients. Early posttransplant infections were similar to those observed in our cohort and included pulmonary, surgical-site and catheter-associated infections. CMV was the most frequently described opportunist. In conclusion, infections following FCTA were related to anatomical, technical and donor/recipient factors. CMV disease occurred in D+/R- recipients after prophylaxis, but was not associated with rejection.

Non-tuberculous mycobacterial infection among lung transplant recipients: a 15-year cohort study.

BACKGROUND: The incidence of infection with non-tuberculous mycobacteria (NTM) after lung transplant is insufficiently defined. Data on the impact of NTM infection on lung transplant survival are conflicting. METHODS: To quantify the incidence and outcomes of colonization and disease with NTM in patients after lung transplantation, the medical records, chest imaging, and microbiology data of 237 consecutive lung transplant recipients between 1990 and 2005 were reviewed. American Thoracic Society (ATS)/Infectious Diseases Society of America and Centers for Disease Control criteria were used to define pulmonary NTM disease and NTM surgical-site infections (SSI), respectively. Incidence rates for NTM colonization and disease were calculated. Comparisons of median survival were done using the log-rank test. RESULTS: NTM were isolated from 53 of 237 patients (22.4%) after lung transplantation over a median of 25.2 months of follow-up. The incidence rate of NTM isolation was 9.0/100 person-years (95% confidence interval [CI), 6.8-11.8), and the incidence rate of NTM disease was 1.1/100 person-years (95% CI 0.49-2.2). The most common NTM isolated was Mycobacterium avium complex (69.8%), followed by Mycobacterium abscessus (9.4%), and Mycobacterium gordonae (7.5%). Among these 53 patients, only 2 patients met ATS criteria for pulmonary disease and received treatment for M. avium. One patient had recurrent colonization after treatment, the other one was cured. Four of the 53 patients developed SSI, 3 caused by M. abscessus and 1 caused by Mycobacterium chelonae. Three of these patients had persistent infection requiring chronic suppressive therapy and one died from progressive disseminated disease. A total of 47 (89%) patients who met microbiologic but not radiographic criteria for pulmonary infection were not treated and were found to have only transient colonization. Median survival after transplantation was not different between patients with transient colonization who did not receive treatment and those who never had NTM isolated. CONCLUSION: Episodic isolation of NTM from lung transplant recipients is common. Most isolates occur among asymptomatic patients and are transient. Rapidly growing NTM can cause significant SSI, which may be difficult to cure. NTM disease rate is higher among lung transplant recipients than in the general population. In this cohort, NTM isolation was not associated with increased post-transplantation mortality.

Reversible left hemispheric ischemia secondary to carotid compression in Eagle syndrome: surgical and CT angiographic correlation.

Symptoms of ipsilateral carotid artery compression secondary to an elongated styloid process or calcified stylohyoid ligament may be seen in Eagle syndrome. The patient will typically experience cervicofacial pain due to stimulation of the arterial nervous plexus. In addition, symptoms directly attributable to compression of the carotid artery may be seen, including visual symptoms and syncope. We report here the case of a patient who developed symptoms consistent with left hemispheric ischemia within 15 seconds of turning his head to the left. These symptoms were completely reversible on returning the head to the neutral position. No long-term sequelae were detected clinically or radiographically.

Candida albicans-induced inflammatory response in human keratinocytes.

Candida albicans strains 3153a, ATCC 48867, CBS 2730, DSM 70014, and Vir 13 were cultivated and sterile C. albicans filtrates were produced. The interaction of soluble Candida factors of these infiltrates with human HaCaT keratinocytes was assayed in vitro. The following parameters were analyzed: cell proliferation, protein synthesis, nuclear matrix protein (NMP) 41 release, cytokine release (IL-1beta, soluble IL-2 receptor, IL-6, and IL-8), and reactive oxygen species (ROS). Cell counts at 1, 12, and 24 h were significantly lower for C. albicans strains CBS 2730 and VIR 13 (P < 0.05). There was no significant change for the remaining strains. Neither the protein synthesis nor the NMP-41 release was significantly affected. IL-6 and IL-8 were stimulated by C. albicans filtrates to different amounts with higher levels in strains of low virulence. There was no effect on the other cytokines. The production of ROS by HaCaT keratinocytes was suppressed. The induction of an inflammatory keratinocyte response by soluble C. albicans factors may play a role among the host-yeast interactions.

Inhibition of signal transduction in EGF-dependent epithelial cell lines.

The epidermal growth factor (EGF) receptor plays a pivotal role in growth regulation of epidermal keratinocytes. Its expression and function can be markedly altered during malignant transformation in squamous cell carcinoma. The present study investigated the potential of growth inhibition by signal-transduction inhibitors in EGF-dependent epithelial cell lines in vitro. Benign HaCaT keratinocytes and malignant A431 cells were grown in vitro and exposed to various concentrations of a panel of eleven kinase and phosphodiesterase inhibitors. Cell growth was measured after 24 h and 48 h using fluorescence labeling with Hoechst 33342 and propidium iodide. Significant growth inhibition was achieved with all inhibitors when applied to HaCaT cells. The strongest growth inhibition was achieved with inhibitors H-7, A3 and diacylglycerol kinase inhibitors I and II. A431 cells were inhibited significantly by H-7, A3 and H-9. Selected signal-transduction inhibitors such as A3, H-7 and H-9 acting on intracellular kinases are capable of suppressing growth of EGF-dependent benign and malignant epithelial cell lines in vitro. They might be of future potential in the treatment of epithelial cancer but further studies are necessary.

An HPLC tracing of the enhancer regulation in selected discrete brain areas of food-deprived rats.

The recent discovery of the enhancer regulation in the mammalian brain brought a different perspective to the brain-organized realization of goal-oriented behavior, which is the quintessence of plastic behavioral descriptions such as drive or motivation. According to this new approach, 'drive' means that special endogenous enhancer substances enhance the impulse-propagation-mediated release of transmitters in a proper population of enhancer-sensitive neurons, and keep these neurons in the state of enhanced excitability until the goal is reached. However, to reach any goal needs the participation of the catecholaminergic machinery, the engine of the brain. We developed a method to detect the specific enhancer effect of synthetic enhancer substances [(-)-deprenyl, (-)-PPAP, (-)-BPAP] by measuring the release of transmitters from freshly isolated selected discrete brain areas (striatum, substantia nigra, tuberculum olfactorium, locus coeruleus, raphe) by the aid of HPLC with electrochemical detection. To test the validity of the working hypothesis that in any form of goal-seeking behavior the catecholaminergic and serotonergic neurons work on a higher activity level, we compared the amount of norepinephrine, dopamine, and serotonin released from selected discrete brain areas isolated from the brain of sated and food-deprived rats. Rats were deprived of food for 48 and 72 hours, respectively, and the state of excitability of their catecholaminergic and serotonergic neurons in comparison to that of sated rats was measured. We tested the orienting-searching reflex activity of the rats in a special open field, isolated thereafter selected discrete brain areas and measured the release of norepinephrine, dopamine, and serotonin from the proper tissue samples into the organ bath. The orienting-searching reflex activity of the rats increased proportionally to the time elapsed from the last feed and the amount of dopamine released from the striatum, substantia nigra and tuberculum olfactorium, that of norepinephrine released from the locus coeruleus and that of serotonin released from the raphe increased significantly in the hungry rats proportionally to the time of fasting. For example: the amount of dopamine released from the substantia nigra of sated rats (4.62 +/- 0.20 nmoles/g wet weight) increased to 5.95 +/- 0.37 (P < 0.05) and 10.67 +/- 0.44 (P < 0.01) in rats deprived of food for 48 and 72 hours, respectively.

A pharmacological analysis elucidating why, in contrast to (-)-deprenyl (selegiline), alpha-tocopherol was ineffective in the DATATOP study.

The Parkinson Study Group who conducted the Deprenyl and Tocopherol Antioxidative Therapy of Parkinsonism (DATATOP) trial designed their study in the belief that the MAO inhibitor (-)-deprenyl (selegiline), the antioxidant alpha-tocopherol, and the combination of the two compounds will slow the clinical progression of the disease to the extent that MAO activity and the formation of oxygen radicals contribute to the pathogenesis of nigral degeneration. In fact, (-)-deprenyl only delayed the onset of disability associated with early, otherwise untreated Parkinson's disease, however, in contrast to the expectation of the authors, alpha-tocopherol proved to be ineffective in the DATATOP study. Enhancer substances, (-)-deprenyl, (-)-1-phenyl-2-propylaminopentane [(-)-PPAP] the (-)-deprenyl analogue free of MAO inhibitory potency, and R-(-)1-(benzofuran-2-yl)-2-propylaminopentane [(-)-BPAP] the presently known most potent enhancer substance, are peculiar stimulants. They enhance the impulse propagation mediated release of the catecholamines in the brain. Due to their enhancer effect, the amount of catecholamines released from selected discrete brain areas (striatum, substantia nigra, tuberculum olfactorium, locus coeruleus) is significantly higher in rats treated with an enhancer substance than in saline treated rats. We compared the effect of (-)-deprenyl 0.025 and 0.25 mg/kg, (-)-PPAP 0.1 mg/kg, (-)-BPAP 0.0001 mg/kg, and alpha-tocopherol 25 and 50 mg/kg, in this test. The doses of (-)-deprenyl and alpha-tocopherol were selected to be in compliance with the dose given in the DATATOP study. Compared to saline treated rats, the enhancer substances significantly increased the amount of dopamine released from the striatum, substantia nigra and tuberculum olfactorium and the amount of norepinephrine released from the locus coeruleus; alpha-tocopherol was ineffective. The results indicate that alpha-tocopherol was ineffective, because, unlike (-)-deprenyl it dose not enhance the activity of the nigrostriatal dopaminergic neurons.

Serum matrix metalloproteinase-2 in patients with malignant melanoma.

PURPOSE: Matrix metalloproteinases (MMPs) are a family of structurally related zinc-dependent endopeptidases that are able to degrade extracellular matrix components. MMPs play a role in tumor invasion and tumor metastasis. MMP-2 (also known as gelatinase A) is expressed in human melanoma cells. METHODS: In this study, we measured MMP-2 in 337 serum probes of 166 melanoma patients with a recently developed enzyme immunoassay and compared these data with the tumor stage, presence of metastases, and the levels of S100beta and soluble intracellular adhesion molecule-1 (sICAM-1) in serum. RESULTS: The mean levels were (189.2 +/- 50.8) ng/ml for MMP-2, (263.2 +/- 74.1) ng/ml for sICAM-1, and (0.424 +/- 1.568) U/ml for S100beta. There was a statistical significant correlation of MMP-2 with sICAM-1 (P=0.05) and Sl00beta (P=0.01). The mean MMP-2 levels (in ng/ml) in patients with metastatic melanoma were 196.4 +/- 54.0 versus 182.6 +/- 46.9 in non-metastasizing melanoma (P=0.037). However, there was no significant difference in MMP-2 levels between the different tumor stages. CONCLUSION: Determination of MMP-2 serum levels is of limited value as a tumor marker in melanoma, though there are higher levels in the more advanced disease.

Melatonin reduces UV-induced reactive oxygen species in a dose-dependent manner in IL-3-stimulated leukocytes.

Reactive oxygen species (ROS) are presumed to be involved in inflammatory UV reactions of the skin. This in vitro study was performed to investigate the suppressive effect of melatonin in interleukin-3 (IL-3) stimulated leukocytes. Neutrophilic granulocytes were isolated from EDTA-treated whole blood and placed in a phosphate-buffered saline (PBS) containing IL-3. Cell suspensions were either treated with PBS (control) or with increasing doses of melatonin (0.1, 0.5, 1, 2, 3, 5, 7.5, 10 mmol). One PBS solution was left unirradiated and the other nine solutions (PBS and melatonin) were irradiated with 750 mJ/cm2 UVB light (280-360 nm, max: 310 nm). Radical formation was measured by the chemiluminescence technique. UV-irradiated leukocytes showed a 5-fold higher radical formation than unirradiated leukocytes. Melatonin, in increasing doses in powers of ten, led to a maximum suppression of free radicals at 10 nmol (P= 0.01) and 1 mmol melatonin (P= 0.001), showing a biphasic, non-linear, dose response relationship. Melatonin, given in amounts of 0.1-10 mmol, led to a direct dose-dependent suppression of ROS. Radical formation was suppressed significantly in a range from 0.5 to 10 mmol (P= 0.001). Melatonin is known to function as a radical scavenger and antioxidant; some of these melatonin effects may be receptor independent, while others may be receptor dependent.

Graded expression patterns of ephrin-As in the superior colliculus after lesion of the adult mouse optic nerve.

The idea has been put forward that molecules and mechanisms acting during development are re-used during regeneration in the adult, for example in response to traumatic injury in order to re-establish the functional integrity of neuronal circuits. Members of the Eph family of receptor tyrosine kinases and their 'ligands', the ephrins, play a prominent role during development of the retinocollicular projection in rodents, where EphA receptors and ephrin-As are expressed in gradients in both the retina and the superior colliculi (SC). We were interested in investigating whether EphA family members are also expressed or re-expressed in the adult after optic nerve lesion, since the presence of axon guidance information is an important prerequisite for a topographically appropriate re-connection by retinal ganglion cell (RGC) axons. This analysis was encouraged by results showing that RGC axons do not exert guidance preferences in response to membranes from adult unlesioned SC, but in response to membranes from the adult deafferented SC. We found a graded expression pattern of ephrin-As in the SC both before and after deafferentation, which was remarkably similar to those found during development. EphA receptor levels were reduced in the SC after deafferentation and the expression patterns of the EphB family were not changed. In particular, the presence of a graded ephrin-A expression in the deafferented SC suggests that - if robust regeneration of RGC axons can be achieved - topographic guidance information as a likely requirement for a functionally successful re-establishment of the retinocollicular projection is available.