Biomedical subjects
S Varma
Publications and source records attributed to S Varma.
ATRA syndrome with extensive organ infiltration.
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BDNF overexpression increases dendrite complexity in hippocampal dentate gyrus.
There is increasing evidence that brain-derived neurotrophic factor (BDNF) modulates synaptic and morphological plasticity in the developing and mature nervous system. Plasticity may be modulated partially by BDNF's effects on dendritic structure. Utilizing transgenic mice where BDNF overexpression was controlled by the beta-actin promoter, we evaluated the effects of long-term overexpression of BDNF on the dendritic structure of granule cells in the hippocampal dentate gyrus. BDNF transgenic mice provided the opportunity to investigate the effects of modestly increased BDNF levels on dendrite structure in the complex in vivo environment. While the elevated BDNF levels were insufficient to change levels of TrkB receptor isoforms or downstream TrkB signaling, they did increase dendrite complexity of dentate granule cells. These cells showed an increased number of first order dendrites, of total dendritic length and of total number of branch points. These results suggest that dendrite structure of granule cells is tightly regulated and is sensitive to modest increases in levels of BDNF. This is the first study to evaluate the effects of BDNF overexpression on dendrite morphology in the intact hippocampus and extends previous in vitro observations that BDNF influences synaptic plasticity by increasing complexity of dendritic arbors.
Occupational contact dermatitis from a garlic and herb mixture.
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Allergic contact dermatitis from polyvinylpyrrolidone (PVP)/1-triacontene copolymer in a sunscreen.
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Case 3: vulval crohn's disease (VCD).
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Tattoo ink darkening of a yellow tattoo after Q-switched laser treatment.
The popularity of tattoos is burgeoning with 20-30 million tattooed individuals in the Western World. Requests for removal can be expected to rise concurrently with increased applications. Laser removal of tattoos is potentially a more cosmetically acceptable method of removing tattoos than surgical excision or dermabrasion. Nevertheless, complications and side-effects can result from laser treatment and include scarring, hypopigmentation, hyperpigmentation, partial removal, infection, bleeding and tattoo ink darkening. The latter has been reported for flesh-toned and red tattoos. Such a complication has never been reported for the laser treatment of a yellow tattoo in the dermatological literature. We describe a case of tattoo ink darkening of a yellow tattoo after treatment with the 532 nm quality-switched Neodymium : Ytrrium-Aluminium Garnet laser to highlight clinicopathological features. The mechanism by which some tattoos darken after laser treatment is not clearly understood. We review darkening of tattoos after laser treatment to raise awareness of this important complication. This paper will help to facilitate discussions with the patient and in obtaining informed consent prior to commencing treatment. Tattoo ink darkening of a yellow tattoo adds to the growing list of complications resulting from attempts at tattoo removal.
Epidural abscess and Staphylococcus aureus endocarditis - a rare association.
Epidural abscess is a relatively uncommon disorder. Although the surgical management is the mainstay of treatment, there are case reports of it being managed conservatively in selected patients. We report a patient who presented with quadreparesis due to epidural abscess and had infective endocarditis due to Staphylococcus aureus septicemia. Both epidural abscess and infective endocarditis were managed conservatively with intravenous antibiotics given for four weeks, with complete recovery of patient.
Velopharyngeal incompetence and chromosome 22q11 deletion.
Chromosome 22q11 deletion gives rise to various phenotypes, including cardiac malformations, velopharyngeal abnormalities, absent thymus, and neurological defects. We assessed, in a prospective study, chromosome 22q11 deletion in 50 of 144 patients with velopharyngeal incompetence in the absence of overt clefting. 18 (12.5% of the whole cohort and 36% of patients tested for the deletion) had the 22q11 deletion. This frequency differs from an estimated population prevalence of 0.025% and suggests a need for screening for the 22q11 deletion in these patients.
VEGF increases permeability of the endothelial cell monolayer by activation of PKB/akt, endothelial nitric-oxide synthase, and MAP kinase pathways.
VEGF is a key regulator of vascular permeability. However, its signaling pathways are incompletely understood. We tested the hypothesis that VEGF regulates endothelial cell (EC) permeability by activating PKB/akt, NOS, and MAP kinase dependent pathways using human umbilical vein EC (HUVEC). Permeability was measured from FITC-dextran 70-kDa flux across the EC monolayer at baseline and after VEGF at 0.034, 0.068, 1, 10, and 100 nM. VEGF increased HUVEC permeability to FITC-dextran in a dose-dependent manner. VEGF (1 nM) increased permeability from 3.9 x 10(-6) +/- 0.7 x 10(-6) to 14.0 x 10(-6) +/- 1.7 x 10(-6) cm/s (mean +/- SEM; P < 0.001). Permeability changes were also assessed after treatment with 1, 10, and 100 nM wortmannin (PI 3-kinase inhibitor); 0.01, 0.1, and 1.0 nM LY294002 (PI 3-kinase inhibitor); 200 microM l-NMMA (NOS inhibitor); 2.7 microM AG126 (p42/44(MAPK) inhibitor); and 0.006, 0.06, and 0.6 microM SB203580 (p38(MAPK) inhibitor). All inhibitors blocked VEGF-induced permeability changes. Our data demonstrate that (1) VEGF increases permeability of EC monolayers in a dose-dependent fashion, and (2) VEGF-induced permeability is mediated through PI-3 kinase-PKB, NOS, and MAP-kinase signaling cascades. These observations suggest that microvascular hyperpermeability associated with inflammation and vascular disease is mediated by activation of these EC signaling pathways.
Bowen's disease, solar keratoses and superficial basal cell carcinomas treated by photodynamic therapy using a large-field incoherent light source.
BACKGROUND: Photodynamic therapy (PDT) has not yet been demonstrated to be superior to conventional treatment in the treatment of superficial skin cancers and premalignant skin conditions. A limitation for PDT is the absence to date of a light source suitable for the treatment of larger lesions or 'field changes' where several lesions are present on one anatomical site. OBJECTIVES: To investigate the safety and efficacy of a large field light source, the Waldmann PDT 1200, in the treatment of Bowen's disease (BD), superficial basal cell carcinomas (BCCs) and solar keratoses (SKs). METHODS: After application of 5-aminolaevulinic acid for 4-6 h, each lesion was irradiated with 105 J cm-2 of incoherent red light centred on 640 nm. Eighty-eight patients with 239 lesions were recruited. RESULTS: Within two treatments, 88% of BD lesions, 95% of BCCs and 99% of SKs showed complete clinical clearance. At 12 months the complete response rates were 69% for BD, 82% for BCC and 72% for SK. CONCLUSIONS: This study confirms that PDT is a useful treatment and that selected superficial BCCs and SKs respond well to PDT. The PDT 1200 light source proved capable of treating multiple lesions amounting to a 'field change' and also lesions up to 10 cm in diameter within an acceptable treatment time. Thus far, PDT has failed to become established as a routine treatment for small premalignant and malignant skin lesions as it has not proved superior to simple cheaper conventional therapies such as cryotherapy, curettage and cautery, topical chemotherapy with 5-fluorouracil, or surgery. However, PDT has become established as a treatment for selected cases in some centres. This study suggests a role for PDT in the treatment of large premalignancies, superficial BCCs and field change where existing treatments may be problematic.
Dystrophic calcinosis cutis in venous ulcers: a cause of treatment failure.
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Audit of a melanoma screening day in the U.K.: clinical results, participant satisfaction and perceived value.
BACKGROUND: The incidence of cutaneous malignant melanoma (MM) has risen significantly over the last 50 years in caucasian populations. Mortality is related to the Breslow thickness of the lesion, and early detection followed by complete surgical excision is crucial to reducing this. Skin screening events have been advocated as a means of detecting greater numbers of MMs in the earlier and thinner stages. OBJECTIVES: To assess the feasibility and effectiveness of this approach in the U.K. METHODS: The Department of Dermatology, Singleton Hospital, Swansea, U.K. offered a 1-day melanoma screening event in summer 1998 at which 832 consecutive individuals were seen. A postal questionnaire 1 year after the event audited participant perceived value and satisfaction. RESULTS: Three MMs were identified (yield 1 : 277), all < 0.75 mm in thickness. Despite high participant satisfaction and perceived value, the pick-up rate of malignancy was significantly lower than at rapid access pigmented lesion clinics. CONCLUSIONS: In a country such as the U.K., with comprehensive health coverage and a low incidence of MM, triage for melanoma and referral to specialists by general practitioners may be more cost and time effective.
Severe cutaneous reaction to CS gas.
Tear gas is used throughout the World for control of riots and civil disobedience. CS gas as used by the UK police force is issued as a 'spray' and is 5% CS in methylisobutylketone (MIBK), a potent irritant. Assaults on police officers in forces issued with CS spray have fallen significantly over the past 3 years, whilst having risen in areas without it. Thus, CS gas appears to be an effective deterrent. However, significant cutaneous reactions can occur as a result of exposure. We report a severe contact dermatitis to CS gas to highlight the clinical features. The nature of CS gas and potential cutaneous adverse reactions are discussed.
Hyposplenism in alcoholic cirrhosis, facts or artifacts? A comparative analysis with non-alcoholic cirrhosis and extrahepatic portal venous obstruction.
BACKGROUND AND AIMS: Hyposplenism has been described in patients with alcoholic cirrhosis (AC). However, no data are available regarding hyposplenism in patients with non-alcoholic cirrhosis (NAC) and other forms of portal hypertension such as extrahepatic portal venous obstruction (EHPVO). The aim is to study the splenic functions in patients with AC, NAC, and EHPVO. METHODS: Splenic functions were assessed consecutively in 22 patients with AC, 21 with NAC, and 23 with EHPVO. The tests included pitted red blood cells (RBC; %) and Howell-Jolly bodies in the peripheral smear. Pitted RBCs > 2% with or without the presence of Howell-Jolly bodies were taken as indicators of hyposplenism. The splenic function in each group was compared with age-matched controls. RESULTS: Hyposplenism was found in 10 (45.45%) patients with AC, six (28.57%) with NAC and one (4.34%) with EHPVO. The mean pitted RBCs were significantly increased in patients with AC (mean 4.93 +/- 1.36% vs control 1.22 +/- 0.17%, P < 0.05), but not so with NAC (2.01 +/- 0.69%) and EHPVO (mean 0.99 +/- 0.1% vs control 0.66 +/- 0.1%, P > 0.05). Howell-Jolly bodies were seen in only four patients. The mean pitted RBCs were significantly higher among patients who were actively consuming alcohol (9.14 +/- 3.35%) compared to those who abstained at least for more than 24 weeks (2.0 +/- 1.3%, P < 0.05). CONCLUSION: Hyposplenism is more common in AC patients, particularly those who are actively consuming alcohol compared with those who abstain. Patients with NAC have a lower incidence of hyposplenism, while in EHPVO patients, it is uncommon.
Malignant atrophic papulosis (Degos' disease): clinicopathological correlations.
Malignant atrophic papulosis (MAP) is a rare disease characterized by pathognomonic cutaneous lesions and frequently fatal systemic involvement. Dermatologists should have a high index of suspicion for systemic complications in a patient presenting with MAP. We report a case of malignant atrophic papulosis to highlight the clinicopathological features and review this important dermatological diagnosis.
Crescentic glomerulonephritis associated with renal cell carcinoma.
Various glomerular lesions are described in association with malignancy. We report a rare case of crescentic glomerulonephritis occurring in association with renal cell carcinoma. A granular deposition of immune complexes and complement strongly suggests a tumor associated immune complex glomerulonephritis.
A papillary lesion on the foreskin.
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