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Biomedical subjects

N Francis

Publications and source records attributed to N Francis.

At least 37 records · Page 2Linked to original sources
PubMed2001

Rosai-Dorfman disease complicated by autoimmune haemolytic anaemia: case report and review of a multisystem disease with cutaneous infiltrates.

We report a patient with sinus histiocytosis with massive lymphadenopathy (Rosai-Dorfman disease) who presented with widespread nodal and extranodal involvement affecting the skin, orbits and nasal sinuses, complicated by the development of autoimmune haemolytic anaemia. The aetiology and pathogenesis of this multisystem disorder are unknown but are thought to represent a reactive histiocytic process to an infective agent rather than a neoplastic or other primary condition. Prognosis is generally good but clinical or laboratory evidence of immune dysfunction tends to predict a poorer outcome. We describe the clinical course of the patient and review the literature on this disease.

Adult↗
PubMed2001

Pyoderma gangrenosum of the eyelid and acute rhinosinusitis.

Pyoderma gangrenosum (PG) is a destructive, necrotizing, noninfective ulceration of the skin. Periorbital PG is extremely rare, and may progress, with eventual loss of the eye. We report a 47-year-old woman who presented with a right periorbital swelling of 8 days duration and concurrent acute rhinosinusitis. A clinical diagnosis of right periorbital PG was made, and treatment instituted with intravenous methylprednisolone and antibiotics, resulting in rapid resolution of the condition. The clinical features in this case, together with the past history of histologically confirmed PG, enabled a rapid diagnosis to be made, with early administration of treatment resulting in minimal scarring. The clinical picture could easily be confused with periorbital cellulitis, and this case demonstrates the importance of considering the differential diagnoses of periorbital swelling.

Acute Disease↗
PubMed2001

Clinico-pathological features of relapsing very thin melanoma.

In the UK the incidence of malignant melanoma is increasing and more patients with thinner primary lesions are diagnosed earlier. Most patients with very thin melanoma (< 0.76 mm Breslow thickness) are cured by surgical excision, however, 2-18% relapse over 0-11 years with local or distant metastatic disease and may die. There are still no recognized prognostic or predictive, clinical, serological or molecular markers that accurately determine which of these very thin melanoma will relapse: the Breslow thickness remains the single most important prognostic factor for melanoma in general. Improved prognostic indicators are therefore needed for this rare, but important, unusually aggressive group, to better direct new invasive and expensive investigations and treatment. This article reviews the clinical and histological aspects of relapsing very thin melanoma and discusses the findings of several recent studies, including our own. There is no clinical or biological evidence to support either wide surgical excision or sentinel node biopsy in these patients.

Back↗
PubMed2001

Central and peripheral adverse hemodynamic changes during laparoscopic surgery and their reversal with a novel intermittent sequential pneumatic compression device.

OBJECTIVE: To study the influence of a novel intermittent sequential pneumatic compression device (Lympha-press) on the adverse cardiac and peripheral hemodynamic changes induced by positive-pressure pneumoperitoneum (PPPn) in laparoscopic surgery. SUMMARY BACKGROUND DATA: Creation of PPPn is known to cause adverse central and peripheral hemodynamic changes. An intrasubject observational study was undertaken to quantitate these adverse changes and to assess the influence of an intermittent sequential pneumatic compression system on these adverse hemodynamic changes during laparoscopic surgery with PPPn. METHODS: The study involved 16 consecutive patients undergoing laparoscopic surgery with PPPn of 12 mmHg and 30 degrees head-up tilt position. The following peripheral hemodynamic recordings were made using Doppler ultrasound: peak systolic velocity (PSV), end diastolic velocity (EDV), and cross-sectional area of the femoral vein. Central monitoring included cardiac output and stroke volume by transesophageal Doppler, blood pressure, and pulse. The hemodynamic state based on these parameters was assessed before induction of PPPn with the anesthetized patient in the supine position, after induction of PPPn and head-up tilt position with Lympha-press off, and during PPPn and head-up tilt position with Lympha-press on, and after desufflation with the patient in the supine position under general anesthesia. RESULTS: Positive-pressure pneumoperitoneum and the head-up tilt position resulted in a 33% reduction in PSV, a 21% reduction in EDV, and a 29% increase in cross-sectional area of the femoral vein. This was associated with a 20% reduction in cardiac output and an 18% reduction in stroke volume. Activation of Lympha-press during PPPn and the head-up tilt position resulted in a 129% increase in PSV and a 55% increase in EDV by 55%. It also increased the cardiac output by 27% and stroke volume by 16%, with no effect on cross-sectional area. Compared with the pre-PPPn stage, there was no difference in cardiac output or stroke volume, but the PSV was higher by 78% and the EDV by 32%. After abdominal desufflation in the supine position, the cardiac output and stroke volume were restored to the pre-PPPn level, but persistent and significant elevations were observed during the period of study in PSV, EDV, and cross-sectional area. CONCLUSIONS: Significant and individually variable central and peripheral hemodynamic changes are encountered during laparoscopic surgery with PPPn and the head-up tilt position. These are reversed by intermittent sequential pneumatic compression using Lympha-press.

Adult↗
PubMed2000

Regulation of transcription in the neuronal nicotinic receptor subunit gene cluster by a neuron-selective enhancer and ETS domain factors.

Expression of neurotransmitter receptors encoded by the nicotinic acetylcholine receptor (nAchR) subunit gene cluster depends on coexpression of the beta4, alpha3, and alpha5 subunits in certain kinds of neurons. One way in which coexpression might be achieved is through the regulation of promoters in the cluster by neuron-selective enhancers. The beta43' enhancer is located between the beta4 and alpha3 promoters and it directs cell type-specific expression in cell lines. It is not known, however, whether beta43' is active in neurons. Therefore, we assayed beta43' in dissociated rat sympathetic ganglia cultures, which contain nAchR-positive neurons as well as nAchR-negative non-neuronal cells. Reporters controlled by the alpha3 promoter and beta43' were expressed in a neuron-selective manner; greater than 90% and up to 100% of luciferase expression was detected in neurons. Neuron selectivity was maintained when beta43' was placed next to ubiquitously active viral promoters. In contrast, replacing beta43' with the SV40 enhancer eliminated neuron selectivity. The enhancer is composed of at least two separate but functionally interdependent elements, each of which interacts with a different type of ETS domain factor. These findings support a model in which beta43' controls neuronal expression of one or more genes in the cluster through interactions with a combination of ETS factors.

Animals↗
PubMed2000

Transcriptional control of the neuronal nicotinic acetylcholine receptor gene cluster by the beta43' enhancer, Sp1, SCIP and ETS transcription factors.

Receptors assembled from the products of a neuronal beta4alpha3alpha5 NAChR gene cluster depend on these genes being coordinately regulated in particular populations of neurons. Little is known, however, about the transcriptional mechanisms that are likely to underlie their co-expression in correct neuronal cell types. We have identified several regulatory elements and transcription factors that influence transcription of the alpha3 and beta4 genes. The promoters of these genes appear to contain a common cis element that binds Sp1 transcription factors. They can be activated by the POU-domain factor SCIP and activation does not require SCIP binding sites. Between these two promoters is a cell type specific enhancer called beta43'. This enhancer has little activity in non-neuronal cells and is preferentially active in particular populations of central neurons. The clustered genes are potential targets of ETS factors as the ETS domain factor, Pet-1 can activate beta43'-dependent transcription. The neuron-selective properties of beta43' and its location suggest that it is a component of the cis regulatory information required to control expression of the beta4 and alpha3 genes in specific populations of neurons.

Animals↗
PubMed2000

Barraquer-Simons lipodystrophy, Raynaud's phenomenon and cutaneous vasculitis.

We report a 32-year-old man who presented with a 2-year history of unexplained weight loss and symptoms of Raynaud's phenomenon. Clinical examination and investigations were consistent with a diagnosis of acquired partial lipodystrophy (Barraquer-Simons disease). This patient also exhibited an associated cutaneous vasculitis and peripheral perniotic changes. He had normal renal function and glucose tolerance and no immunological abnormality has been detected in his serum to date. The absence of C3-nephritic factor in the presence of overt lipodystrophy suggests that there may be another factor or immunological mediator responsible for the subcutaneous changes seen in patients with lipodystrophy.

Adult↗
PubMed1999

The ETS domain factor Pet-1 is an early and precise marker of central serotonin neurons and interacts with a conserved element in serotonergic genes.

Serotonin (5-HT) plays a crucial neuromodulatory role in numerous physiological and behavioral functions, and dysfunction of the serotonergic system has been implicated in several psychiatric disorders. Despite the widespread importance of the central serotonergic neurotransmitter system, little is known about the molecular mechanisms controlling the development of 5-HT neurons. We previously identified an ETS domain transcription factor, Pet-1, that is expressed in a small number of tissues, including the brain. Here, we show that expression of Pet-1 RNA in the brain is restricted to, and marks, the entire rostrocaudal extent of rat serotonergic hindbrain raphe nuclei. Remarkably, Pet-1 RNA colocalizes with tryptophan hydroxylase-positive neurons in raphe nuclei but not with their nonserotonergic neuron or non-neuronal neighbors. Pet-1 RNA is limited to two domains in the developing hindbrain, which precedes the appearance of 5-HT in each domain by approximately a half day. Conserved Pet-1 binding sites are present in or near the promoter regions of the human and mouse 5-HT1a receptor, serotonin transporter, tryptophan hydroxylase, and aromatic L-amino acid decarboxylase genes whose expression is characteristic of the serotonergic neuron phenotype. These sites are capable of supporting transcriptional activation through interactions with the Pet-1 ETS domain and can function as enhancers. Together, our findings establish Pet-1 as an early and precise marker of 5-HT neurons and suggest that it functions specifically in the differentiation and maintenance of these neurons.

Animals↗
PubMed1999

NT-3, like NGF, is required for survival of sympathetic neurons, but not their precursors.

Superior cervical ganglia of postnatal mice with a targeted disruption of the gene for neurotrophin-3 have 50% fewer neurons than those of wild-type mice. In culture, neurotrophin-3 increases the survival of proliferating sympathetic precursors. Both precursor death (W. ElShamy et al., 1996, Development 122, 491-500) and, more recently, neuronal death (S. Wyatt et al., 1997, EMBO J. 16, 3115-3123) have been described in mice lacking NT-3. Consistent with the second report, we found that, in vivo, neurogenesis and precursor survival were unaffected by the absence of neurotrophin-3 but neuronal survival was compromised so that only 50% of the normal number of neurons survived to birth. At the time of neuron loss, neurotrophin-3 expression, assayed with a lacZ reporter, was detected in sympathetic target tissues and blood vessels, including those along which sympathetic axons grow, suggesting it may act as a retrograde neurotrophic factor, similar to nerve growth factor. To explore this possibility, we compared neuron loss in neurotrophin-3-deficient mice with that in nerve growth factor-deficient mice and found that neuronal losses occurred at approximately the same time in both mutants, but were less severe in mice lacking neurotrophin-3. Eliminating one or both neurotrophin-3 alleles in mice that lack nerve growth factor does not further reduce sympathetic neuron number in the superior cervical ganglion at E17.5 but does alter axon outgrowth and decrease salivary gland innervation. Taken together these results suggest that neurotrophin-3 is required for survival of some sympathetic neurons that also require nerve growth factor.

Animals↗
PubMed1999

Treatment of grade 3 anal intraepithelial neoplasia by complete anal mucosal excision without fecal diversion: report of a case.

PURPOSE: The aim of this study was to remove completely the risk of malignant transformation without permanent or temporary fecal diversion in a patient with extensive anal intraepithelial neoplasia. METHODS: All anal canal mucosa and the lowest 1.5 cm of rectal mucosa were excised and the adjacent rectal mucosa and submucosa advanced to the anal verge skin. RESULTS: The patient achieved normal continence within a month after the operation. Multiple anal canal biopsies at 12 months after the operation revealed normal rectal mucosa. CONCLUSIONS: Total anal mucosal excision offers a relatively simple means of removing the malignant risk of anal intraepithelial neoplasia without fecal diversion in selected patients.

Anus Neoplasms↗
PubMed1999

Cutaneous granulomas associated with high-grade T-cell non-Hodgkin's lymphoma.

We describe a patient with non-Hodgkin's lymphoma treated with a chemotherapy regimen (which included bleomycin, prednisolone and low-dose methotrexate) who developed cutaneous non-caseating granulomas. We felt our patient fitted into the category of 'sarcoid-like granulomas'.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1999

Itchy folliculitis and human immunodeficiency virus infection: clinicopathological and immunological features, pathogenesis and treatment.

The predominant itchy folliculitis associated with human immunodeficiency virus (HIV) infection appears to be an eosinophilic folliculitis (EF). This is characterized by lytic degeneration of sebaceous glands and an inflammatory infiltrate in which eosinophils and CD8+ T lymphocytes predominate. All patients have low CD4 counts and present late on in their HIV disease. Lesional distribution is mainly truncal, with a significant proportion also having facial involvement. Our prospective survey has shown that it is impossible to differentiate clinically between infective folliculitis and EF, and we recommend therefore that all cases are biopsied. We review the clinicopathological and immunological aspects of HIV-associated itchy folliculitis, in particular HIV-associated EF as well as current theories on pathogenesis and treatment. We suggest that HIV-associated EF is an autoimmune disease with the sebocyte or some constituent of sebum acting as the autoantigen.

AIDS-Related Opportunistic Infections↗
PubMed1999

The perils and pitfalls of penile injections.

We describe a 45-year-old man who presented with an indurated penile nodule following self-injection of acyclovir tablets which he had dissolved in hydrogen peroxide solution. This is a hazardous procedure which may be complicated by permanent deformity and functional disability due to the irritant nature of the tablets' constituents and their propensity to cause foreign body reactions in the skin.

Acyclovir↗