Cutaneous squamoproliferative lesions in kidney transplant recipients: an investigation of specific Epstein-Barr virus expression

In a previous report we demonstrated Epstein-Barr virus expression in cutaneous squamous cell carcinomas from heart transplant recipients. In a comparative study, skin lesions from renal allograft recipients were investigated for the presence of Epstein-Barr virus. Thirty cutaneous squamoproliferative lesions from 10 kidney transplant recipients were examined for Epstein-Barr virus-specific gene expression. The techniques used for detection were polymerase chain reaction, in situ hybridization and immunohistochemistry. Epstein-Barr virus DNA was not detected by polymerase chain reaction in the neoplasias, and only single Epstein-Barr virus-positive carcinoma cells were shown by in situ hybridization in three cases of infiltrative squamous cell carcinomas. Immunohistochemistry for Epstein-Barr virus latent membrane protein 1 showed a negative result in all samples. These findings differ from our earlier investigations of cutaneous squamous cell carcinomas from heart transplant recipients where Epstein-Barr virus expressions were common. This may indicate that the part Epstein-Barr virus plays in the development of post-transplant, cutaneous squamoproliferative disorders is related to type of organ transplantation and/or grade of immunosuppression.     

Effects of adenovirus-mediated sorcin overexpression on excitation-contraction coupling in isolated rabbit cardiomyocytes

To evaluate the effect of sorcin on cardiac excitation-contraction coupling, adult rabbit ventricular myocytes were transfected with a recombinant adenovirus coding for human sorcin (Ad-sorcin). A beta-galactosidase adenovirus (Ad-LacZ) was used as a control. Fractional shortening in response to 1-Hz field stimulation (at 37 degrees C) was significantly reduced in Ad-sorcin-transfected myocytes compared with control myocytes (2.10+/-0.05% [n=311] versus 2.42+/-0.06% [n=312], respectively; P<0.001). Action potential duration (at 20 degrees C) was significantly less in the Ad-sorcin group (458+/-22 ms, n=11) compared with the control group (520+/-19 ms, n=10; P<0.05). In voltage-clamped, fura 2-loaded myocytes (20 degrees C), a reduced peak-systolic and end-diastolic [Ca2+]i was observed after Ad-sorcin transfection. L-type Ca2+ current amplitude and time course were unaffected. Caffeine-induced Ca2+ release from the sarcoplasmic reticulum (SR) and the accompanying inward Na+-Ca2+ exchanger (NCX) current revealed a significantly lower SR Ca2+ content and faster Ca2+-extrusion kinetics in Ad-sorcin-transfected cells. Higher NCX activity after Ad-sorcin transfection was confirmed by measuring the NCX current-voltage relationship. beta-Escin-permeabilized rabbit cardiomyocytes were used to study the effects of sorcin overexpression on Ca2+ sparks imaged with fluo 3 at 145 to 160 nmol/L [Ca2+] using a confocal microscope. Under these conditions, caffeine-mediated SR Ca2+ release was not different between the two groups. Spontaneous spark frequency, duration, width, and amplitude were lower in sorcin-overexpressing myocytes. In summary, sorcin overexpression in rabbit cardiomyocytes decreased Ca2+-transient amplitude predominantly by lowering SR Ca2+ content via increased NCX activity. The effect of sorcin overexpression on Ca2+ sparks indicates an effect on the ryanodine receptor that may also influence excitation-contraction coupling.     

The E/e filling index and right ventricular pressure in relation to applied international Doppler recommendations of left ventricular filling assessment.

AIM: A ratio>15 between the early diastolic pulsed Doppler velocities of the mitral inflow (E) and the basal left ventricular (LV) tissue (e) has been demonstrated to predict an elevated LV filling pressure (FP). An elevated LVFP implies an elevated right ventricular pressure (RVp). In order to investigate the sensitivity of the E/e filling index, we compared E/e and RVp, in their ability to identify a Doppler-assumed elevation of LVFP. METHODS AND RESULTS: Application of pulsed Doppler international recommendations grouped 134 patients with acute coronary syndromes (ACS) and 50 age- and sex-matched controls, according to LV filling: normal; delayed relaxation; an isolated pathological mitral-pulmonary venous-A-wave-duration difference; pseudo normal; or a restrictive filling pattern. An E/e>15 and an RVp>30 mmHg showed the following (%) sensitivity (32/94), specificity (95/76), positive (68/59), and negative (80/97) predictive values of a Doppler-assumed elevation of LVFP, in terms of either a pseudo normal or a restrictive filling pattern. CONCLUSION: The low sensitivity of E/e to detect a Doppler-assumed elevation of LVFP could limit its clinical usefulness as a single variable, in ACS. The high sensitivity and negative predictive value of RVp support its use as an additional LV filling variable in these patients.     

Inter-reader agreement of interpretation of radiological course of bile duct changes between serial follow-up magnetic resonance imaging/3D magnetic resonance cholangiopancreatography of patients with primary sclerosing cholangitis

Abstract

Objectives: Interpretation of MRI/MRCP in primary sclerosing cholangitis (PSC) at a single time point has low inter-reader agreement. Agreement of interpretation of the dynamic course of duct changes in follow-up MRI/MRCP is of clinical importance but remains unknown. Our aims are therefore to assess the inter-reader agreement of interpretation of the course of duct changes in PSC and investigate if elimination of 3?D MRCP affects inter-reader agreement.

Materials and Methods: We studied 40 consecutive PSC-patients who underwent two liver MRI/MRCPs at two time points. Two readers independently evaluated the course of duct changes between the two time points in two imaging sets, one with and one without 3?D MRCP. The intraclass correlation coefficient (ICC) was calculated for evaluation of inter-reader and intra-reader agreement between the two time points and two imaging sets accordingly.

Results: Inter-reader agreement of the interpretation of the course of duct changes between the two time points was poor (ICC up to 0.224). Elimination of 3?D MRCP neither improved inter-reader agreement which was again poor (ICC up to 0.26) nor did it change considerably the way readers interpret the course of ducts changes (ICC for intra-reader agreement between 0.809 and 0.978).

Conclusions: Inter-reader agreement of the interpretation of radiological course of duct changes is poor in serial follow-up MRI/MRCP of PSC-patients. Elimination of 3?D MRCP does not increase inter-reader agreement but maintains an excellent intra-reader agreement for the interpretation of the dynamic course of bile duct changes.

• Key points

• Inter-reader agreement of interpretation of radiological course of bile duct changes between serial follow-up MRI/MRCP examinations of patients with PSC is poor.

• Absence of 3D MRCP does not affect considerably the way readers interpret the radiological course of bile ducts changes.

• When MRCP is absent or of low quality, utilization of other sequences seems to be helpful as an alternative for bile duct evaluation.

     

Local fever illness classifications: implications for home management of malaria strategies

BACKGROUND: The Ugandan Ministry of Health has adopted the WHO Home Based Fever Management strategy (HBM) to improve access to antimalarial drugs for prompt (<24 h) presumptive treatment of all fevers in children under 5 years. Village volunteers will distribute pre-packed antimalarials free of charge to caretakers of febrile children 2 months to 5 years ('Homapaks'). OBJECTIVE: To explore the local understanding and treatment practices for childhood fever illnesses and discuss implications for the HBM strategy. METHODS: Focus Group Discussions were held with child caretakers in three rural communities in Kasese district, West Uganda, and analysed for content in respect to local illness classifications and associated treatments for childhood fevers. RESULTS: Local understanding of fever illnesses and associated treatments was complex. Some fever illness classifications were more commonly mentioned, including 'Fever of Mosquito', 'Chest Problem', 'the Disease', 'Stomach Wounds' and 'Jerks', all of which could be biomedical malaria. Although caretakers refer to all these classifications as 'fever' treatment differed; some were seen as requiring urgent professional western treatment and others were considered severe but 'non-western' and would preferentially be treated with traditional remedies. CONCLUSIONS: The HBM strategy does not address local community understanding of 'fever' and its influence on treatment. While HBM improves drug access, Homapaks are likely to be used for only those fevers where 'western' treatment is perceived appropriate, implying continued delayed and under-treatment of potential malaria. Hence, HBM strategies also need to address local perceptions of febrile illness and adapt information and training material accordingly.     

Current standards in the diagnostics and therapy of hair diseases – hair consultation

Hair and scalp diseases present an extensive diagnostic and therapeutic task. Treating them is often a challenge for the physician in daily practice. Unclear diagnoses, chronic conditions with long‐lasting therapies and the uncertainty of the patient may often lead to unsatisfying situations for both the patient as well as the doctor. The complaints can be divided into (1) hair loss, (2) increased hair growth and (3) abnormal hair quality. A structured history and the objectification of the clinical findings with the help of standardized diagnostic methods and score systems or classifications enable a diagnosis in most patients already at the first visit. Moreover, such structured processes strengthen the treatment satisfaction and compliance of both the patient and the therapist. In the meantime, diagnostic measures and clinical practice guidelines are available for the most common hair disorders. Expertise in basic psychosomatic care and an empathetic approach to the fears and concerns as well as practical advice for the daily contact with hair disorders should be integrated as separate elements in the management of hair diseases; in most cases they are gratefully welcomed by the patients. The aim of this article is to provide the physician with a guideline for the structured management of a hair patient. An overview of recent new developments and the currently available clinical practice guidelines for diagnosis and therapy of hair disorders is presented.     

Decreased cerebrospinal fluid neuropeptide Y (NPY) in patients with treatment refractory unipolar major depression: preliminary evidence for association with preproNPY gene polymorphism

Extensive animal studies suggest neuropeptide Y (NPY) to be involved in coping with a wide range of stressors, and that impaired central NPY signalling could be involved in the pathophysiology of anxiety and depression. Human studies of central NPY levels in depression have, however, been inconclusive. Here, we examined levels of NPY-like immunoreactivity (NPY-LI) in the cerebrospinal fluid (CSF) of medication-free subjects with treatment refractory unipolar depression. Patients were admitted to a research inpatient unit, examined under standardized conditions, and compared with a sample of volunteers in whom psychiatric morbidity was excluded. A robust suppression of NPY levels in patient CSF was found, while other putative CSF markers (monoamine metabolites, somatostatin) did not differ between the groups. We then explored whether this finding might be related to a recently described T1128C coding polymorphism which results in a Leu7-> Pro7 substitution of the signal peptide, and a previously not described T -399C polymorphism in the promoter region of the preproNPY gene. Preliminary evidence was found for an association of both markers with a diagnosis of depression, indicating the possibility of an underlying haplotype influencing the vulnerability for developing depressive illness. Our present findings are in line with an extensive animal literature, and further support the notion that impaired NPY function could contribute to depressive illness.