Potential of fibroblast cell therapy for recessive dystrophic epidermolysis bullosa.

Recessive dystrophic epidermolysis bullosa (RDEB) is a severe inherited skin-blistering disorder caused by mutations in the COL7A1 gene that lead to reduced type-VII collagen and defective anchoring fibrils at the dermal-epidermal junction (DEJ). Presently there are no effective treatments for this disorder. Recent mouse studies have shown that intradermal injections of normal human fibroblasts can generate new human type-VII collagen and anchoring fibrils at the DEJ.

Heritable gene repression through the action of a directed DNA methyltransferase at a chromosomal locus.

The ability to exogenously impose targeted epigenetic changes in the genome represents an attractive route for the simulation of genomic de novo epigenetic events characteristic of some diseases and for the study of their downstream effects and also provides a potential therapeutic approach for the heritable repression of selected genes. Here we demonstrate for the first time the ability of zinc finger peptides to deliver DNA cytosine methylation in vivo to a genomic integrated target promoter when expressed as fusions with a mutant prokaryotic DNA cytosine methyltransferase enzyme, thus mimicking cellular genomic de novo methylation events and allowing a direct analysis of the mechanics of de novo DNA methylation-mediated gene silencing at a genomic locus. We show that targeted methylation leads to gene silencing via the initiation of a repressive chromatin signature at the targeted genomic locus.

Oncostatin M receptor-beta mutations underlie familial primary localized cutaneous amyloidosis.

Familial primary localized cutaneous amyloidosis (FPLCA) is an autosomal-dominant disorder associated with chronic skin itching and deposition of epidermal keratin filament-associated amyloid material in the dermis. FPLCA has been mapped to 5p13.1-q11.

Attitudes and awareness of female genital mutilation: a questionnaire-based study in a Kenyan hospital.

There are considerable efforts in Kenya to increase awareness of the issues and health risks associated with female genital mutilation (FGM) through educational programmes. The Kenyan government formally outlawed FGM in 2001. This questionnaire-based study aimed to explore attitudes and awareness of FGM in Kenya with particular reference to the law, health complications and educational programmes.

The filaggrin story: novel insights into skin-barrier function and disease.

Recent reports have uncovered the key role of the protein filaggrin in maintaining an effective skin barrier against the external environment. Loss-of-function mutations in the profilaggrin gene (FLG) are common and are present in up to 10% of the population. These mutations are the cause of the semi-dominant skin-scaling disorder ichthyosis vulgaris and are a major risk factor for the development of atopic dermatitis.

Genetic diseases of junctions.

Tight junctions, gap junctions, adherens junctions, and desmosomes represent intricate structural intercellular channels and bridges that are present in several tissues, including epidermis. Clues to the important function of these units in epithelial cell biology have been gleaned from a variety of studies including naturally occurring and engineered mutations, animal models and other in vitro experiments. In this review, we focus on mutations that have been detected in human diseases.

CCL21 expression pattern of human secondary lymphoid organ stroma is conserved in inflammatory lesions with lymphoid neogenesis.

CCL21 is a homeostatic lymphoid chemokine instrumental in the recruitment and organization of T cells and dendritic cells into lymphoid T areas. In human secondary lymphoid organs (SLOs), CCL21 is produced by cells distributed throughout the T zone, whereas high endothelial venules (HEVs) lack CCL21 mRNA. A critical question remains whether the development of ectopic lymphoid tissue (ELT) in chronic inflammation recapitulates the features of SLOs.

Lymphoid tissue reactions in rheumatoid arthritis.

Frequently, the immune cell infiltrate of chronically inflamed tissues develops functional germinal centres and acquires structural features of secondary lymphoid organs. Ectopic lymphoid structures occur in peripheral tissues not only during autoimmune diseases but also in tumors (reactive infiltrate), chronic infections and graft rejection, indicating a strong link between lymphoid neogenesis and persistent antigen driven immune/inflammatory responses. There has been a renewed interest in ectopic lymphoid neogenesis, as better understanding of the mechanisms underpinning this process could contribute to elucidate the bio-pathological mechanisms involved in transition from acute-self resolving to chronic immunological aggression as well as identify novel therapeutic targets.

The molecular basis of lipoid proteinosis: mutations in extracellular matrix protein 1.

Lipoid proteinosis (OMIM 247100), also known as Urbach-Wiethe disease or hyalinosis cutis et mucosae, is a rare autosomal recessive disorder characterized by generalized thickening and scarring of the skin and mucosae. In 2002, the disorder was mapped to a locus on chromosome 1q21 and pathogenic mutations were identified in the ECM1 gene, which encodes for the glycoprotein extracellular matrix protein 1 (ECM1). ECM1 has since been shown to have several important biological functions.

Unusual molecular findings in Kindler syndrome.

Kindler syndrome (KS) is a rare inherited skin disorder with blistering and poikiloderma as its main clinical features. It is caused by loss-of-function mutations in the C20orf42 (KIND1) gene which encodes kindlin-1, an actin cytoskeleton-focal contact-associated protein which is predominantly expressed in keratinocytes. We investigated the molecular basis of KS in a 16-year-old Indian boy who had additional clinical findings, including scleroatrophic changes of the hands and feet, pseudoainhum and early onset of squamous cell carcinoma on his foot.

Botulinum toxin for detrusor overactivity and symptoms of overactive bladder: where we are now and where we are going.

Botulinum toxin (BTX) treatment for overactive bladder and detrusor overactivity is becoming increasingly recognized as an excellent therapeutic option for treating patients refractory to anticholinergic agents. Results from open-label studies have suggested that this therapy is effective in neurogenic and idiopathic detrusor overactivity, yet validating evidence from randomized, placebo-controlled trials has been unavailable. The exact mechanism of action of BTX in the bladder is controversial, although evidence suggests that apart from preventing the presynaptic release of acetylcholine from the parasympathetic innervation to the bladder, it might have an effect on sensory mechanisms.

Communication with older breast cancer patients.

An increasing proportion of patients with breast cancer are aged above 70 at the time of diagnosis and yet this particular age group has been underserved in terms of clinical research. Good communication between a doctor and a patient implies giving the advice and treatment most appropriate to that particular individual's needs, based upon their health and the tumor characteristics in the framework of their experience and belief system. Doctors need to be able to pick up both verbal and nonverbal cues and whenever possible to place the needs of the patient rather than her relatives as paramount.

The effects of AZD3582 [4-(nitroxy)butyl-(2S)-2-(6-methoxy-2-naphthyl) propanoate], and naproxen on key pathogenic steps in NSAID-enteropathy in the rat.

Background: The pathogenesis of NSAID-induced enteropathy may involve dual inhibition of the cyclooxygenase (1 and 2) and a topical effect with sequential increased intestinal permeability, development of inflammation and ulcers. It has been suggested that nitric-oxide donating drugs cause significantly less gastrointestinal injury by counteracting for NSAID-induced reductions in blood flow.

Aims: To compare the effects of AZD3582 [4-(nitroxy)butyl-(2S)-2-(6-methoxy-2-naphthyl) propanoate], and naproxen on key pathogenic steps in NSAID-enteropathy in the rat.

The role of fibroblasts in tissue engineering and regeneration.

Fibroblasts are mesenchymal cells that can be readily cultured in the laboratory and play a significant role in epithelial-mesenchymal interactions, secreting various growth factors and cytokines that have a direct effect on epidermal proliferation, differentiation and formation of extracellular matrix. They have been incorporated into various tissue-engineered products such as Dermagraft (Advanced BioHealing, La Jolla, CA, U.S.

Dose and Frequency of Administration of Interferon-beta Affect its Efficacy in Multiple Sclerosis.

Data reviewed in this article demonstrate that both interferon-beta-1a (IFNbeta-1a) and interferon-beta-1b (IFNbeta-1b) show a dose-response relationship in multiple sclerosis at current clinical doses. Moreover, the efficacy of these therapies is probably dependent on their frequent administration to maintain optimal levels of biological effect. These results differ from the conclusions of a recent review of data comparing two doses of IFNbeta-1a, given intramuscularly once weekly, that showed no difference in efficacy between the two doses.

Randomized double-blind trial of treatment of vitiligo: efficacy of psoralen-UV-A therapy vs Narrowband-UV-B therapy.

Objective: To compare the efficacy of oral psoralen-UV-A (PUVA) with that of narrowband-UV-B (NB-UVB) phototherapy in patients with nonsegmental vitiligo.

Design: Double-blind randomized study.

Setting: Phototherapy unit in a university hospital.

Cervical cerclage: a review.

Cervical cerclage is a common prophylactic intervention that has been used in the management of second trimester loss for several decades, yet it remains one of the more controversial surgical interventions in obstetrics. The diagnosis of cervical insufficiency is notoriously difficult to make, and is usually a retrospective one based on a history of recurrent second trimester loss (or early preterm delivery) following painless cervical dilatation in the absence of contractions, bleeding, or other causes of recurrent pregnancy loss. This article reviews the current literature regarding the efficacy of transvaginal cerclage (in both an elective and emergency setting), therapeutic cerclage (whereby a suture is inserted on the basis of ultrasound evidence of cervical shortening) and transabdominal cerclage.

Maimonides: an early but accurate view on the treatment of haemorrhoids.

Moses Maimonides was not only one of the most influential religious figures of the middle ages, but also a pioneer in a wide variety of medical practices. A brief history of his life, and what is known about his medical education, is given here. His paper on haemorrhoids is summarised, as well as a review of the current understanding of the pathogenesis, prevention and treatment of this common condition.

The teaching of surgery in the undergraduate curriculum. Part II--Importance and recommendations for change.

In the past decade, the teaching of surgery in the undergraduate curriculum has undergone considerable changes in quantity, mode and method of delivery. This is a result of the radical reforms of higher education, the health service and the undergraduate medical curriculum. The changes are complex and require us to ask the questions: how important is the teaching of surgery in the modern medical undergraduate curriculum and is there a need for change? We aim to tackle these questions and propose practical action which medical schools can take to ensure that they deliver effective surgical teaching within the modern medical curriculum and health service.

Preoperative anthropometric analysis of the cleft child's face: a comparison between groups.

This study examines the facial surfaces of different groups of cleft babies aged up to eleven months, prior to any corrective surgery, with the aim of identifying and assessing differences in their facial morphology. Measurements of standard anthropometric landmarks were made on plaster casts taken pre-operatively of the faces of babies presenting for surgical correction of lip and palate deformities. Periorbital and mid face measurements show no difference between control and cleft groups.

An audit and comparative analysis of the kidney transplantation programme in Burma.

Background: The first renal transplant operation to be carried out by a Burmese transplant team was undertaken at the Yangon General Hospital, Burma on the 8th of May 1997. Since then 21 further kidney transplantations have been performed in hospitals in Yangon (Rangoon) and Mandalay. Burma was renamed as Myanmar in 1989.

Involving older people in health research.

Background: It is a UK policy requirement to involve patients and the public in health research as active partners.

Objective: We reviewed published reports of studies which involved older people in commissioning, prioritizng, designing, conducting or disseminating research. Search strategy and selection criteria: systematic searches of databases (PubMed, SCI-EXPANDED, SSCI, A&HCI, ASSIA, Embase, CINAHL and Medline) for English language studies published between 1995 and 2005 which had involved older people as partners n the research process as opposed to research subjects.

Does the referral and selection for NHS-funded dental implant treatment in the UK follow National Guidelines?

Introduction: The Royal College of Surgeons of England (RCSE) has provided a national guideline document detailing specific selection criteria for National Health Service (NHS) dental implant therapy in the UK. The aim of this study was to investigate whether these guidelines are being observed both in the referral and selection of patients.

Patients And Methods: Information was collected prospectively from 8 consecutive implant assessment clinics at Guy's and St Thomas' Hospital Trust over a 6-month period, via a questionnaire concerning the reason for referral for implant treatment, dental/smoking/radiotherapy status, and the consultant decision on whether an application would be made for NHS implant funding.

Construction and validation of a quality of life questionnaire for neuromuscular disease (INQoL).

Background: Because there is no muscle disease specific measure of quality of life (QoL), we wanted to develop and validate an individualized muscle disease specific measure of QoL for adults suitable for both clinical and research use.

Methods: A literature review exploring QoL and its measurement resulted in the development of a theoretical model of QoL. This was used alongside qualitative interviews (n = 41) and a postal survey (n = 252) to design a questionnaire.