Expression of serotonergic receptors in psoriatic skin

Psoriasis appears to be influenced by stress, which causes release of adrenal hormones. Serotonin, or hormonal actions on serotonin and serotonin receptors, may have a role in psoriasis. Distribution of serotonin receptors was studied in involved and noninvolved skin in patients with psoriasis and compared to normal skin, by using immunohistochemistry and antibodies to 5-HT1A, 5-HT2A and 5-HT3 receptors (R). There was a decreased (P<0.001) number of 5-HT1AR positive cells, the majority being tryptase positive, in involved and noninvolved psoriatic papillary dermis, compared to normal skin. 5-HTlAR expression was also found in the upper part of the epidermis, on vessel walls and on melanocytes. 5-HT2AR expressing papillary mononuclear cells, CD3 positive, were increased (P<0.001 and P<0.01, respectively) in involved and noninvolved psoriatic skin, compared to normal skin, an increase (P<0.01) also being found in the involved compared to noninvolved skin. Expression of 5-HT3R could be found in the basal epidermal layer of noninvolved but not in the involved skin of psoriasis, where it was only found in the acrosyringium. The present findings are compatible with the 5-HT1A and 5-HT2A receptors having antagonistic functions, and raise the possibility of using receptor specific drugs in the treatment of psoriasis.     

Dose effects of continuous vinblastine chemotherapy on mammalian angiogenesis mediated by VEGF-A

Low-dose continuous or metronomic chemotherapy with several agents can exert significant antiangiogenic effects, as shown in preclinical studies. Therapy of this kind is generally well tolerated compared with conventional chemotherapy with high, temporally spaced out bolus doses. A critical point emerges when the effects on angiogenesis of low-toxic metronomic doses of chemotherapeutics in preclinical studies are to be transferred to clinical protocols, as there is a risk that a virtually non-toxic dose might also be ineffective; clearly, dose-effect data are important. We therefore sought to investigate whether a dose-dependent response exists in metronomic vinblastine chemotherapy. The surrogate tumor-free rat mesentery model, allowing the study of antiangiogenic effects per se, was used. Following systemically administered metronomic chemotherapy, it closely reflects the indirectly assessed antiangiogenic and growth-retarding effects in a syngenic cancer model. VEGF-A, which is a central proangiogenic factor in most tumors, was administered i.p. to induce angiogenesis in the mesenteric test tissue and, using morphometry, the angiogenesis-modulating effects of vinblastine were assessed in terms of objective quantitative variables. We report that continuous vinblastine treatment with an apparently non-toxic dose (1.0 mg/kg/week or 0.143 mg/kg/day) for 10 days, and a dose that substantially inhibited the physiologic body-weight gain (2.0 mg/kg/week or 0.286 mg/kg/day) for 6 days, demonstrates a dose-response relationship; the high dose significantly suppresses angiogenesis. To our knowledge, no previous study has reported on a dose-dependent antiangiogenic effect by continuous or metronomic vinblastine treatment in a mammalian in vivo model.     

In vitro and in vivo cytotoxic effects of PRIMA-1 on hepatocellular carcinoma cells expressing mutant p53ser249

Hepatocellular carcinoma (HCC) is highly lethal due to limited curative options. In high-incidence regions, such as parts of Africa and Southeastern Asia, >50% of cases carry an AGG to AGT mutation at codon 249 of the TP53 gene, considered as a 'signature' of mutagenesis by aflatoxins. The protein product, p53ser249, may represent a therapeutic target for HCC. The small molecule p53 reactivation and induction of massive apoptosis (PRIMA)-1 has been shown to induce apoptosis in tumour cells by reactivating the transactivation capacity of some p53 mutants. In this study, we have investigated the cytotoxic effects of PRIMA-1 on HCC cells expressing p53ser249. In p53-null Hep3B cells, over-expression of p53ser249 or p53gln248 by stable transfection increased the cytotoxicity of PRIMA-1 at 50 muM. Furthermore, PRIMA-1 treatment delayed the growth of p53ser249-expressing Hep3B cells xenografted in severe combined immunodeficiency mice. However, PRIMA-1 did not restore wild-type DNA binding and transactivation activities to p53ser249 or to p53gln248 in Hep3B cells. Moreover, in PLC/PRF/5, a HCC cell line constitutively expressing p53ser249, small interfering RNA (siRNA) silencing of the mutant increased the cytotoxic effect of PRIMA-1. These apparently contradictory effects can be reconciled by proposing that p53ser249 exerts a gain-of-function effect, which favours the survival of HCC cells. Thus, both inhibition of this effect by PRIMA-1 and removal of the mutant by siRNA can lead to the decrease of survival capacity of HCC cells.     

Cutaneous human papillomavirus 88: remarkable differences in viral load

A human papillomavirus (HPV) was cloned from a patient with multiple squamous cell carcinomas (SCCs) and identified as HPV88, recently categorized into a new species within the genus Gamma. The HPV88 viral load in an SCC of the index patient exceeded 1 million copies/cell. By contrast, a survey of 447 skin lesions (79 actinic keratoses, 73 seborrhoeic keratoses, 169 basal cell carcinomas and 126 SCCs) and 362 healthy skin biopsies found detectable HPV88 DNA in only 7 specimens. All these had very low viral loads (<1 copy/10(3) cells) implying extreme biological variability in viral load.     

Item development for a questionnaire investigating patient self reported perception,satisfaction and outcomes of a single osteopathy in the cranial field (OCF) treatment

BackgroundOsteopathy in the Cranial Field (OCF) is a treatment approach used by osteopaths in the management of a wide variety of complaints. OCF is based on the premise that the bones of the skull are mobile and that changes in the flow of cerebrospinal fluid can affect the function of the body. There are only a few studies assessing the effectiveness of OCF and there is no published research investigating patients' perception of what happens during and post an OCF treatment.ObjectiveTo develop items for a patient self-reported questionnaire that assesses patients' own perceptions of one OCF treatment.DesignSystematic literature search, item development and face validity testing.MethodsA systematic search of the literature was undertaken to identify a measure or measures that may be suitable to assess patient perceptions of OCF. No measure of patient perception of OCF was located. Measures of patient ratings of satisfaction, efficacy and outcomes of physical therapy treatment were located and reviewed. From these published measures, items that were appropriate for a measure of OCF were identified and considered as possible items to include in a new measure of patient perception of OCF. Items were developed and face validity was investigated.ParticipantsSix osteopaths who were familiar with or use OCF as part of their treatment approach, 2 patients who had previously been treated by osteopaths who used OCF exclusively, and 2 patients who had not previously received any OCF treatment as part of their osteopathic treatment.ResultsA systematic literature search was conducted. Appropriate items were extracted from 7 articles in the ‘osteopathy’ search and 4 additional articles from the ‘manual therapy’ search. Items were reworded, where appropriate, to ensure they reflected the OCF approach. Consideration of face validity identified a number of changes that were required to some of the items.ConclusionsThe Patient Perception Measure of Osteopathy in the Cranial Field (PPM-OCF) was developed to assess patient perceptions of the OCF treatment approach. Six domains of patient perception of treatment were identified and 37 items were developed within these 6 domains. Further psychometric testing of the PPM-OCF is required prior to its application in the clinical and research settings.     

Live/Real Time Three‐Dimensional Transesophageal Echocardiographic Assessment of Ventricular Septal Volume and Mass before and after Myectomy in Hypertrophic Cardiomyopathy

Hypertrophic cardiomyopathy (HCM) is the most common genetically transmitted cardiomyopathy. In patients resistant to medical management, myectomy is the surgical procedure of choice to reduce the symptoms of left ventricular outflow obstruction. Two‐dimensional transesophageal echocardiography (2DTEE) has become part of the operative procedure by decreasing the incidence of postoperative complications. However, because of the three‐dimensional geometry of left ventricular outflow tract, it is unable to comprehensively assess the location and severity of the obstruction and to provide accurate guidance during myectomy. In this study, 10 patients with HCM underwent live/real time three‐dimensional transesophageal echocardiography (3DTEE) intra‐operatively to measure the volume of the resected septum. This volume correlated well with the volume of the resected septal muscle directly obtained using a graduating cylinder containing water (r = 0.9, P < 0.000). 3DTEE may be potentially used as an adjunct to guide the surgeon in performing an adequate myectomy with a lower incidence of residual obstruction and complications such as an iatrogenic ventricular septal defect.     

TracheobronchiaI Clearance in Twins

Tracheobronchial clearance was studied with a lest aerosol of 6μ-7μ monodisperse fluorinated ethylene propylene (Teflon 120) particles tagged with technetium 99m (half-life, 6.0 hours) and external measurements of the radioactivity in the lungs. Nine pairs of monozygotic and nine pairs of dizygotic twins were studied. The clearance patterns in the monozygotic pairs were highly similar. In the dizygotic pairs there was a tendency to similarity. Among the pairs there was a remarkable difference in the clearance patterns, Consequently the result indicates that tracheobronchial clearance to a great extent is constitutionally determined. The medical implications of this are discussed.     

Immediate diagnosis of ventriculits: evaluation of parameters independent of microbiological culture

Background  

Generally accepted reference values in CSF diagnostics are not valid in cerebrospinal fluid (CSF) containing large amounts of blood. Residual blood may obscure ventriculitis as diagnostics largely depend on parameters such as cell count, lactic acid and total protein measurement. We sought to improve the diagnostics by evaluating a cytokine panel and soluble CD62L as markers of ventriculitis. In addition, we tested an algorithm of established parameters to predict ventriculitis in a specific patient collective.     

The interpreter’s voice: Carrying the bilingual conversation in interpreter-mediated consultations in pediatric oncology care

Objectives

The objective of this study was to explore interpreters’ perceived strategies in the interaction in interpreter-mediated consultations between healthcare personnel and patients/families with limited Swedish proficiency in pediatric oncology care.

The vascular response to long-term extended contact lens wear

The effects of long-term extended wear of soft contact lenses on human conjunctival and limbal vasculature were determined by examining 27 patients who had worn a high water content hydrogel contact lens in one eye only for an average of 62 ± 29 months (mean ± SD). The levels of general conjunctival hyperaemia (p > 0.01), limbal hyperaemia (p > 0.001), and the extent of limbal vessel penetration (p > 0.001) were found to be significantly greater in the lens-wearing eye, relative to the control eye, immediately on lens removal. The patients ceased lens wear for up to one month, and changes in the levels of vascular response were monitored during this period. General conjunctival hyperaemia and limbal hyperaemia recovered to levels observed in the non-lens-wearing eye within two and seven days after lens removal, respectively. However, limbal vessel penetration was still significantly greater in the lens-wearing eye 33 days after ceasing lens wear (p > 0.05).