Hypohidrotic ectodermal dysplasia with atrophic rhinitis and nasal myiasis.

Hypohidrotic/anhidrotic ectodermal dysplasia is a rare inherited disorder characterized by hypohidrosis/anhidrosis, hypotrichosis, dysodontia and heat intolerance. Most common mode of transmission is X-linked recessive, showing complete expression in males, and only partial manifestations in the female carrier heterozygotes. Features like atrophic rhinitis, nasal and aural myiasis, syndactyly, cleft lip and/or palate, mental retardation and immunodeficiency are uncommonly seen in this syndrome. We hereby report a case of hypohidrotic ectodermal dysplasia with unusual features of atrophic rhinitis and nasal myiasis.

Disseminated rhinosporidiosis with unusual involvement of the nail apparatus.

Rhinosporidiosis is an uncommon chronic granulomatous disease caused by Rhinosporidium seeberi. It primarily affects the nasal mucosa and the nasopharynx. The disease may disseminate to the skin, larynx, trachea, genitalia, bones and even the internal organs. Although simultaneous onset of nasal and disseminated lesions has been reported, dissemination usually occurs several years after the onset of nasal lesions. We report a rare case of disseminated rhinosporidiosis involving both nares, the nasal mucosa, nasopharynx, oral cavity and oropharynx, as well as widespread cutaneous lesions over the trunk and the limbs with nail involvement. This last feature has not, to our knowledge, been previously reported.

Non-healing ulcer on the great toe due to cellular schwannoma.

Cellular schwannoma (CS) occurring in the foot is uncommon, and when it does occur, it usually presents as a slowly growing tumour. Ulceration of CS on the foot is rare. We report a 20-year-old woman who presented with a painful and non-healing ulcer on the lateral area of the right great toe, which failed to heal despite treatment. Six months after onset of the ulcer, a small swelling appeared below it. Histological examination of a biopsy taken from the edge of the ulcer established the diagnosis of CS. Preoperative magnetic resonance imaging delineated the mass on the lateral area of the right great toe. The mass was surgically excised, which led to resolution of the symptoms. This case highlights the fact that chronic ulcers in the foot can be due to CS. Correct diagnosis and management depend on a histopathological diagnosis.

Kumkum-induced dermatitis: an analysis of 46 cases.

Kumkum is a commonly used cosmetic in India, traditionally based on turmeric powder, and its ingredients can cause various types of dermatosis. We undertook a study to characterize kumkum-induced dermatitis clinically and to identify by patch testing the allergens involved. In total, 46 patients with kumkum-induced dermatitis (mean age of these cases 46.5 years; female : male ratio 1.8 : 1) were investigated. The forehead was the most commonly involved site (31/46), followed by the glabellar area (16/46), hair parting (6/46), abdomen (5/46), and neck (3/46). Pigmented contact dermatitis was seen in 35 patients (76.1%), and allergic contact dermatitis in 11 patients (23.9%). In total, 25 patients were patch tested. The commonest positive allergic reaction was to thimerosal (18/25, 72%), followed by gallate mix (12/25, 48%). Para-phenylenediamine, Kathon CG, benzotriazol, tert-butyl hydroquinone and parabens gave a reaction for one patient each (1/25, 4%). Patch testing with kumkum was positive in 7 of 13 patients tested.

A cardiac myocyte vascular endothelial growth factor paracrine pathway is required to maintain cardiac function.

The role of the cardiac myocyte as a mediator of paracrine signaling in the heart has remained unclear. To address this issue, we generated mice with cardiac myocyte-specific deletion of the vascular endothelial growth factor gene, thereby producing a cardiomyocyte-specific knockout of a secreted factor. The hearts of these mice had fewer coronary microvessels, thinned ventricular walls, depressed basal contractile function, induction of hypoxia-responsive genes involved in energy metabolism, and an abnormal response to beta-adrenergic stimulation. These findings establish the critical importance of cardiac myocyte-derived vascular endothelial growth factor in cardiac morphogenesis and determination of heart function. Further, they establish an adult murine model of hypovascular nonnecrotic cardiac contractile dysfunction.

Elevation of vitreous leptin in diabetic retinopathy and retinal detachment.

PURPOSE: Leptin is a cytokine that regulates energy metabolism and is linked to diabetes mellitus through its metabolic actions. Leptin is angiogenic and promotes wound healing, and therefore this investigation was conducted to determine whether leptin is associated with neovascular and fibrotic complications of diabetes and other retinopathies. METHODS: Serum and vitreous samples were collected from patients classified by the presence and type of diabetic retinopathy or other ocular diseases. Leptin was measured in serum and vitreous by radioimmunoassay, and leptin and leptin receptor were localized in epiretinal membranes immunohistochemically. RESULTS: Leptin levels in serum and vitreous were higher in patients with diabetes than in those without, and vitreous leptin concentrations were especially elevated in patients with proliferative diabetic retinopathy or retinal detachment. Leptin and leptin receptor were detected in fibrovascular epiretinal membrane of patients with diabetes. CONCLUSIONS: Leptin in human vitreous is elevated in proliferative diabetic retinopathy, and retinal detachment and is present in fibrovascular epiretinal tissue. These data suggest an involvement of leptin in retinal disease.

In vivo formation of complex microvessels lined by human endothelial cells in an immunodeficient mouse.

We have identified conditions for forming cultured human umbilical vein endothelial cells (HUVEC) into tubes within a three-dimensional gel that on implantation into immunoincompetent mice undergo remodeling into complex microvessels lined by human endothelium. HUVEC suspended in mixed collagen/fibronectin gels organize into cords with early lumena by 24 h and then apoptose. Twenty-hour constructs, s.c. implanted in immunodeficient mice, display HUVEC-lined thin-walled microvessels within the gel 31 days after implantation. Retroviral-mediated overexpression of a caspase-resistant Bcl-2 protein delays HUVEC apoptosis in vitro for over 7 days. Bcl-2-transduced HUVEC produce an increased density of HUVEC-lined perfused microvessels in vivo compared with untransduced or control-transduced HUVEC. Remarkably, Bcl-2- but not control-transduced HUVEC recruit an ingrowth of perivascular smooth-muscle alpha-actin-expressing mouse cells at 31 days, which organize by 60 days into HUVEC-lined multilayered structures resembling true microvessels. This system provides an in vivo model for dissecting mechanisms of microvascular remodeling by using genetically modified endothelium. Incorporation of such human endothelial-lined microvessels into engineered synthetic skin may improve graft viability, especially in recipients with impaired angiogenesis.

Control of apoptosis during angiogenesis by survivin expression in endothelial cells.

Mechanisms controlling endothelial cell survival during angiogenesis were investigated. Stimulation of quiescent endothelial cells with mitogens, including vascular endothelial growth factor and basic fibroblast growth factor, induced up to approximately 16-fold up-regulation of the cell cycle-regulated apoptosis inhibitor survivin. Mitogen stimulation rapidly increased survivin RNA expression in endothelial cells, which peaked after 6 to 10 hours in culture and decreased by 24 hours. Inflammatory cytokines, tumor necrosis factor alpha, and interleukin-1 did not induce survivin expression in endothelial cells. Formation of three-dimensional vascular tubes in vitro was associated with strong induction of survivin in endothelial cells, as compared with two-dimensional cultures. By immunohistochemistry, survivin was minimally expressed in endothelium of nonproliferating capillaries of normal skin, whereas it became massively up-regulated in newly formed blood vessels of granulation tissue in vivo. Recombinant expression of green fluorescent protein survivin in endothelial cells reduced caspase-3 activity and counteracted apoptosis induced by tumor necrosis factor alpha/cycloheximide. These findings identify survivin as a novel growth factor-inducible protective gene expressed by endothelial cells during angiogenesis. Therapeutic manipulation of survivin expression and function in endothelium may influence compensatory or pathological (tumor) angiogenesis.

Biological action of leptin as an angiogenic factor.

Leptin is a hormone that regulates food intake, and its receptor (OB-Rb) is expressed primarily in the hypothalamus. Here, it is shown that OB-Rb is also expressed in human vasculature and in primary cultures of human endothelial cells. In vitro and in vivo assays revealed that leptin has angiogenic activity. In vivo, leptin induced neovascularization in corneas from normal rats but not in corneas from fa/fa Zucker rats, which lack functional leptin receptors. These observations indicate that the vascular endothelium is a target for leptin and suggest a physiological mechanism whereby leptin-induced angiogenesis may facilitate increased energy expenditure.

Prevention of sporogony of Plasmodium falciparum and P. berghei in Anopheles stephensi mosquitoes by transmission-blocking antimalarials.

The sporontocidal activity of three 8-aminoquinolines, a 1,4-naphthoquinone, and three dihydroacridine-diones was determined against the ANKA clone of Plasmodium berghei and both chloroquine-sensitive (NF54) and chloroquine-resistant (7G8) P. falciparum. Anopheles stephensi mosquitoes previously fed on P. berghei--infected mice or P. falciparum--infected cultures were refed on uninfected mice treated previously with a given drug. Sporontocidal activity was determined by assessing both oocyst and sporozoite development. Neither primaquine nor menoctone exhibited sporontocidal activity against P. berghei or either strain of P. falciparum at a dose of 100 mg base drug/kg mouse body weight, whereas the other five compounds each effectively interrupted the sporogonic development of all three parasite strains at this dose. These data clearly demonstrate that experimental dihydroacridine-diones and 8-aminoquinolines are capable of interrupting the sporogonic development of P. berghei and chloroquine-sensitive and chloroquine-resistant P. falciparum. These data also suggest that the P. berghei model may be used to accurately predict sporontocidal activity against P. falciparum.

Use of ultrasound in osteomyelitis.

The use of ultrasound in osteomyelitis has been studied in 25 patients clinically suspected of osteomyelitis. A sonographic diagnosis of osteomyelitis was made if fluid was present in direct contact with the bone, without intervening soft tissues. This was thought to represent an inflammatory exudate dissecting in a subperiosteal and/or extraperiosteal location. Ultrasonographically 15 patients were found to have osteomyelitis, proved either by surgical drainage or needle aspiration. Seven patients had soft-tissue abscesses, one had cellulitis and two patients had no abnormality.