Extremely low frequency electromagnetic fields modulate expression of inducible nitric oxide synthase, endothelial nitric oxide synthase and cyclooxygenase-2 in the human keratinocyte cell line HaCat: potential therapeutic effects in wound healing.

BACKGROUND: Extremely low frequency (ELF) electromagnetic fields (EMF) are known to produce a variety of biological effects. Clinical studies are ongoing using EMF in healing of bone fractures and skin wounds. However, little is known about the mechanisms of action of ELF-EMF. Several studies have demonstrated that expression and regulation of nitric oxide synthase (NOS) and cyclooxygenase-2 (COX-2) are vital for wound healing; however, no reports have demonstrated a direct action of ELF-EMF in the modulation of these inflammatory molecules in human keratinocytes. OBJECTIVES: The present study analysed the effect of ELF-EMF on the human keratinocyte cell line HaCaT in order to assess the mechanisms of action of ELF-EMF and to provide further support for their therapeutic use in wound healing. METHODS: Exposed HaCaT cells were compared with unexposed control cells. At different exposure times, expression of inducible NOS (iNOS), endothelial NOS (eNOS) and COX-2 was evaluated by Western blot analysis. Modulation of iNOS and eNOS was monitored by evaluation of NOS activities, production of nitric oxide (NO) and O(2)(-) and expression of activator protein 1 (AP-1). In addition, catalase activity and prostaglandin (PG) E(2) production were determined. Effects of ELF-EMF on cell growth and viability were monitored. RESULTS: The exposure of HaCaT cells to ELF-EMF increased iNOS and eNOS expression levels. These ELF-EMF-dependent increased expression levels were paralled by increased NOS activities, and increased NO production. In addition, higher levels of AP-1 expression as well as a higher cell proliferation rate were associated with ELF-EMF exposure. In contrast, ELF-EMF decreased COX-2 expression, PGE(2) production, catalase activity and O(2)(-) production. CONCLUSIONS: Mediators of inflammation, such as reactive nitrogen and PGE(2), and keratinocyte proliferation are critical for the tissue regenerative processes. The ability of ELF-EMF to upmodulate NOS activities, thus nitrogen intermediates, as well as cell proliferation, and to downregulate COX-2 expression and the downstream intermediate PGE(2), highlights the potential therapeutic role of ELF-EMF in wound healing processes.

Functional infrared imaging of paroxysmal ischemic events in patients with Raynaud's phenomenon.

The use of thermal infrared (IR) imaging together with the study of the thermal recovery from a controlled cold challenge has been proposed in the diagnosis and follow-up of therapeutic response of Raynaud's Phenomenon (RP) and Systemic Sclerosis (SSc). The controlled cold challenge test usually performed during IR investigations may induce a RP in patients with the latter condition. In our Institution we routinely perform capillaroscopy and thermal IR to follow-up SSc patients. In this paper, we describe the thermal recovery patterns shown by two SSc patients (a 40 year-old male with diffuse variant of SSc and a 71 year-old female with a limited variant of SSc) who presented ischemic and paroxysmal RP attack while recovering from the routine controlled cold challenge test. During RP attack, the cutaneous temperature of some fingers continued to decrease for some minutes even after the cessation of the cold stress. To the best of our knowledge, to date, no literature report has documented the thermal behaviour of SSc patients' fingers which occasionally present ischemic and paroxysmal response. Triggering of ischemic RP attack appears to not rely only on morphological and structural finger impairment, but also upon other aspects, like the emotional attitude of the subject and the possible discomfort experienced with the proceeding of the functional cold stress test.

Scaphoid waist fractures fixation with staple. Retrospective study of a not widespread procedure.

INTRODUCTION: In carpal scaphoid fractures, the surgical treatment with screw is considered the gold standard; shape memory staple however presents substantial advantages. The authors report a study on unstable fractures of the scaphoid waist (type B1, B2, B5, according to Herbert classification) treated with shape memory staple on a large sample of patients, with the aim to confirm the usefulness of this method, the quality of reduction and fixation, the functional results, the time of union and the possible complications. MATERIALS AND METHODS: A retrospective analysis of 131 patients with scaphoid waist fractures with minimum follow-up 1 year was performed. Staples were used in all cases; technical details are discussed. Outcome measures were: postoperative pain, flexion-extension wrist range, hand grip strength, radiographic consolidation, work absence. Herbert and Fisher Grading System was used to assess subjective, objective and radiographic results. RESULTS: Consolidation was achieved in all cases of primary fractures (0-30 days) within three months after surgery, and within eight months in all but two cases of delayed unions (operated within 6 months of the injury). Pain was absent at follow-up in 79% of cases, never severe or unbearable, the average flexion-extension range achieved was 112°. Handgrip strength values were comparable to those of contralateral wrist in 75% of cases. Mean time lost at work was 7.4 weeks. No algo-distrophy or malunion were observed. Discussion CONCLUSIONS: Scaphoid waist fractures' treatment with shape memory staple should be considered as an excellent alternative to screw fixation.

TNFalpha and its receptors in psoriatic skin, before and after treatment with etanercept.

Psoriasis is a chronic inflammatory skin condition characterized by inflammatory dermal infiltrate and hyperproliferative keratinocytes. The pathogenesis of this disease is mediated by a dysregulation of the innate immunity and cytokine production. Tumor necrosis factor alpha (TNFalpha) is considered the most important cytokine involved in the pathological mechanism of psoriasis. Recently, several therapies have been introduced for the treatment of psoriasis that try to block TNF alpha activity. Among these treatments etanercept is a fusion protein that specifically targets TNF alpha. We performed a study on twelve psoriatic patients aimed at evaluating the effect of etanercept treatment on the production and expression of TNFalpha and its receptors, in lesional and uninvolved psoriatic skin. We demonstrated that after three month of etanercept treatment at 50 mg/wk, TNF, TNF-RI and TNF-RII immunostaining in lesional and non-lesional skin samples of patients was greatly reduced, suggesting that this treatment not only acts on stable lesional plaques, but also at a very early stage of the disease.

Tannic acid induces in vitro acantholysis of keratinocytes via IL-1alpha and TNF-alpha.

The mechanism of acantholysis in pemphigus vulgaris (PV) is an intriguing argument since several chemical mediators are implicated. We previously reported a central role for IL-1alpha and TNF- alpha, both able to regulate complement activation and plasminogen activators. Very little is known about what triggers the disease (drugs, viruses or food). In this study, we evaluate the molecular role of tannins in acantholysis. By HPLC chromatography we measured tannic acid (TA) and gallic acid (GA) in blister fluid of 4 groups of patients divided according to their dietary habits, including a regular diet, a diet rich in tannins, a diet free of tannins, and a group of pemphigus patients. Blister fluid was obtained from patients using a suction blister apparatus. We show that people with a diet rich in tannins have increased tannin metabolites (TA and GA) in the skin in respect to controls (tannin-rich diet: GA = 194.52+/-2.39 nmol/ml; TA = 348.28+/-1.4 nmol/ml versus tannin-Mediterranean diet: GA = 15.28+/-1.63 nmol/ml; TA = 22.81+/-1.68 nmol/ml). PV patients showed similar values to the Mediterranean diet population (PV patients: GA = 95.8+/-1.97 nmol/ml; TA = 199.09+/-4.15 nmol/ml versus Mediterranean diet: GA = 83.53+/-2.35 nmol/ml; TA = 195.1+/-2.50 nmol/ml). In an in vitro acantholysis system using TA and PV-IgG we show that TA 0.1 mM in NHEK culture is able to induce acantholysis. This effect was able to amplify the acantholytic action of PV-IgG in vitro. A blocking study using anti IL-1 alpha and anti TNF-alpha antibodies showed a reduction in TA-induced acantholysis. Taken together, these results suggest that a diet rich in tannins could be a trigger in genetically predisposed patients. If these data are confirmed, a complementary diet poor in tannins may be useful in patients affected by PV.

Elevated 8-isoprostane levels in basal cell carcinoma and in UVA irradiated skin.

Isoprostanes are prostaglandin isomers produced from the peroxidation of polyunsaturated fatty acids from the cellular membrane. They have been used as a specific index of cellular lipoperoxidation and as an indirect measure of oxidative stress. However, these molecules also present several biological activities. An oxidative environment measured as the presence of other indirect measurements of reactive oxygen species lipoperoxidation has recently been described in basal cell carcinoma, the most frequent type of non-melanoma skin cancer. This study aims to measure the levels of 8-isoprostaglandin F2alpha, an isoprostane widely studied in other models as a by-product of ROS-induced lipid peroxidation, in basal cell carcinoma and in UVA irradiated healthy skin. We found that 8-iso-PGF2 alpha is present in higher levels in BCC specimens compared to healthy non sun-exposed skin, confirming previous studies on the production of lipoperoxidation in this tumor. Moreover, we demonstrated that topical pre-treatment with a compound containing vitamin E is capable of reducing 8-iso-PGF2 alpha formation in UV irradiated skin suggesting a role for isoprostanes in UV induced inflammation and eventually carcinogenesis and confirming the function of vitamin E as an antioxidant in this model.

Acrometastasis: a literature review.

OBJECTIVE: Acrometastases are a rare observation, and account for approximately 0.1% of metastases. Every age can be affected, with a male predominance. The most common primary cancer site is the lung, followed by the colo-rectal, breast and genito-urinary tract. They are most commonly seen in pre-terminal patients with wide-spread disseminated disease. Rarely, they may be the first presentation of occult silent cancer, mimicking a benign condition. There is no standard treatment. We reviewed last 20 years literature in order to describe the most common sites of primary tumours and the more commonly used treatments. MATERIALS AND METHODS: We searched the Cochrane Central Library (CENTRAL), MEDLINE/PubMed (from 1940 to February 2014), SCOPUS database, and EMBASE/Ovid using a combination of controlled vocabulary and text word terms. RESULTS: Lung cancer was the first most common cause of acrometastases both in hands and feet, with 32.9% of all the cases; 20% of cases were renal cell cancer (RCC) metastases, followed by breast (12.9%) and colon (10%). Primary malignancies and site of metastasis (hand vs foot) suggest that the tumour cells reach the bones through the circulation and not the lymphatic system; in foot acrometastases Batson's plexus may play a fundamental role in dissemination. CONCLUSIONS: Treatment depends on staging and tumor extent. Amputation or disarticulation is the most common approach. It allows a wide margin resection and pain control. In some cases palliative treatment with radiation therapy, bisphosphonates and chemotherapy have been attempted with good results. The prognosis of the patients with acrometastases is poor; the mean survival time after diagnosis is 7 (±7) months. Special reference needs to be made to metastasis from renal cell carcinoma; if treated with radical surgical resection and nephrectomy a better outcome and survival rate shall be expected.

Microvascular capillaroscopic abnormalities in rheumatoid arthritis patients.

Microvascular circulation was investigated by nailfold capillaroscopy in 32 patients affected by rheumatoid arthritis (RA). In all the patients elongated and tiny capillaries as well as tortuousity were the main shape abnormalities of the capillary loops. Higher subpapilar venous plexus (SPVP) visibility was evidentiated in patients presenting antinuclear and anti-RANA antibodies. No differences in the capillaroscopic pattern were found between rheumatoid factor positive and rheumatoid factor negative patients. In conclusion, elongated and tortuous capillaries seem to be the main alterations in RA, although they are not specific to the disease and are not correlated with the presence of rheumatoid factor. Higher SPVP visibility may be an expression of the endothelial damage induced by antinuclear antibodies in vessel walls.

Skin reactions due to anti-epileptic drugs: several case-reports with long-term follow-up.

In this study, the clinical findings and management of allergic skin reactions induced by the most used antiepileptic drugs, Lamotrigine (LMT) and Carbamazepine (CBZ), were evaluated. Lamotrigine is an antiepileptic drug recently released in several countries; it is effective for a variety of seizure types in adults and children, both as an add-on agent and in monotherapy, and it is generally well tolerated. Clinical and epidemiologic evidence suggest serious cutaneous reactions to antiepileptic drugs are more likely to occur during the first 8 weeks and they appear to increase when drugs are administered with other anticonvulsants, such as Valproate (VPA). We selected 10 patients who presented an idiosyncratic skin rash when treated with carbamazepine (8 patients) and lamotrigine (2 patients) administered as monotherapy, and we followed up on these patients for several years. Seven reactions were mild/severe cutaneous eruptions; one Toxic Epidermal Necrolysis, a case of Stevens-Johnson and a case of Hypersensitivity Syndrome. All severe skin drug reactions were induced by Carbamazepine. In five patients the AEDs were ceased abruptly (sometimes with the administration of a different molecule), tapered in four and continued unchanged in one. We conclude that the discontinuation of the drug with substitution with another is the most effective treatment and that corticosteroids are helpful in mild cutaneous reactions, while in severe skin reactions, such as Toxic Epidermal Necrolysis, corticosteroids are only a complementary therapy since intravenous immunoglobulins are the first choice treatment.

A case of chromoblastomycosis due to Phialophora verrucosa responding to treatment with fluconazole.

We report the case of a 40-year-old Filippino woman, with a 5-year history of a slowly spreading, painful skin lesion on her left foot. Histological examination showed a dermal, granulomatous infiltrate consisting of neutrophils, histiocytes and lymphocytes, with "sclerotic bodies" in the cytoplasm of phagocytic cells. Mycological culture revealed the presence of Phialophora verrucosa and confirmed the histopathological diagnosis of chromo-blastomycosis. Association of surgical curettage of the exuberant, infected tissue with systemic fluconazole administration gave good therapeutic results with no relevant side effects.

Syphilitic aneurysm of the abdominal aorta.

A case of syphilitic aneurysm of the abdominal aorta is described. This unusual finding may be misdiagnosed as "inflammatory" abdominal aortic aneurysm, another condition associated with an intense periaortic inflammatory reaction. The authors discuss the differential diagnostic problems and the surgical technique advisable in these cases.

The dorsal flap of the first web.

In the first web space region, there are communications between the dorsal arteries which arise from the dorsal branch of the radial artery and the digital arteries of the thumb and the index finger. These allow a distally based flap to be raised in the first dorsal intermetacarpal area. This flap has been used in 15 cases of soft-tissue loss from the thumb and index finger. The donor sites were closed primarily in all but two patients. There were no complications, and the results show that this flap is useful for soft-tissue defects on the tip and the palmar and dorsal surfaces of the thumb. Moreover, it may be used as a "cross-finger" flap.

[Morton's disease: optic and electron microscopy observations]. / La maladie de Morton: observations en microscopie optique et électronique.

The authors performed an optic and electron-microscope investigation above the common digital nerve of the foot, whose fragments had been surgically removed from patients suffering from "Morton metatarsalgia" (neuroma). Histological sections were taken from pre-stenotic swelling in patients with clinical symptoms persisting for one year; perineural thickening without evidence of fibroblastic proliferation could be demonstrated, together with an intraneural deposition of an amorphous substance. In other patients suffering from Morton's disease for a longer time, a more pronounced epineural thickening in the pre-stenotic zone could be shown, with partial replacement of nerve fibers by amorphous substance. In the same patients endoneural fibrositis was seen at the level of the stenosis. Electron-microscopy in patients after one year showed an increase in collagenous endoneural fibers and microfibrils. These histopathological findings suggest a compressive mechanism in the pathogenesis of the damage to the common interdigital nerve in Morton's disease, caused by the extrinsic anatomical structures surrounding the nerve. The so-called "neuroma" can be identified with the pre-stenotic swelling.

[Heyman's operation for the treatment of congenital metatarsus varus]. / L'opération de Heyman pour le traitement du metatarsus varus congénital.

The authors report their experience with the operation of Heyman, i.e. complete release of the tarsometatarsal and intermetatarsal joint for the treatment of congenital metatarsus varus. This operation of Heyman is capable of meeting the requirements of correction if the indications are precise and if the surgical technique is perfect. The operation is indicated in cases of varus over 15 degrees, passively reducible, with good axes of the hindfoot and without bony alterations of the Lisfranc joint, in children between 3 and 8 years old. There should be a dorsal and medial capsulotomy, with section of the medial 2/3 of the plantar aspects of tarsometatarsal and intermetatarsal capsules; the lateral portion, the lateral 1/3 of the capsule and the insertions of the fibularis brevis and tibialis anticus should be spared. A complete capsulotomy is not indicated owing to the risk of dislocation of the tarsometatarsal joint. The correction should be stabilized during the operation by Kirschner wires to avoid a loss of correction when putting the foot in plaster.

["Square sail" flap in median nerve lesions at the wrist. Anatomical elements and review of twenty operated cases]. / Le lambeau à "voile carrée" dans les lésions du nerf médian au poignet. Eléments d'anatomie et revue de vingt cas opérés.

INTRODUCTION: Following an anatomical study on the vascular supply of the upper limb, we propose a new adipo-fascial flap at the wrist. The fat pad of pronator quadratus lies over the muscle and is vascularised by a recurrent branch arising from the anastomotic "cross-road" of the anterior interosseous, radial and ulnar arteries, at the radio-carpal joint. The peripheral extensions of the adipose tissue have to be anchored to the palmar fascia of the muscle in order to hoist the flap as a "square sail". The flap is then distally rotated in order to cover the traumatized median nerve segment at the wrist, for 2.5-3 cm of length. METHODS: The authors present a review of the clinical applications (1995-2001) on painful neuromas of the median nerve at the wrist, where traumatic and iatrogenic injuries frequently occur. The surgical procedure consists of external neurolysis followed by coverage of the nerve using this vascularised flap. RESULTS: The results confirm the usefulness of vascularised fat flaps in creating an optimal perineural environment in terms of biological and mechanical quality. The advantage offered by this particular local flap is that it can be speedily raised. Because of its limited length the flap is only able to cover the median nerve at the level of the carpal tunnel: its indications are therefore very selective but not rare, due to the frequency of median nerve injuries at this level. DISCUSSION: Clinical results were very satisfactory: in the twenty cases reviewed, resolution of the symptoms of algodystrophy and causalgia was consistently observed, sometimes to an extraordinary degree, and associated with an improvement in the neurological deficit.