Asymmetrical voltage response in resonant neurons shaped by nonlinearities.

The conventional impedance profile of a neuron can identify the presence of resonance and other properties of the neuronal response to oscillatory inputs, such as nonlinear response amplifications, but it cannot distinguish other nonlinear properties such as asymmetries in the shape of the voltage response envelope. Experimental observations have shown that the response of neurons to oscillatory inputs preferentially enhances either the upper or lower part of the voltage envelope in different frequency bands. These asymmetric voltage responses arise in a neuron model when it is submitted to high enough amplitude oscillatory currents of variable frequencies. We show how the nonlinearities associated to different ionic currents or present in the model as captured by its voltage equation lead to asymmetrical response and how high amplitude oscillatory currents emphasize this response. We propose a geometrical explanation for the phenomenon where asymmetries result not only from nonlinearities in their activation curves but also from nonlinearites captured by the nullclines in the phase-plane diagram and from the system's time-scale separation. In addition, we identify an unexpected frequency-dependent pattern which develops in the gating variables of these currents and is a product of strong nonlinearities in the system as we show by controlling such behavior by manipulating the activation curve parameters. The results reported in this paper shed light on the ionic mechanisms by which brain embedded neurons process oscillatory information.

Detection of chest pain of non-cardiac origin at the emergency room by a new non-invasive device avoiding unnecessary admission to hospital.

Recent advances in the treatment of acute coronary syndromes has raised awareness that prompt presentation for chest pain may be life saving. Most patients presenting with chest discomfort have a non-ischaemic ECG on presentation, but are routinely admitted to hospital because of diagnostic uncertainty for occult MI or ischaemia. We tested a new non-invasive device that measures central aortic pressure changes (dP/dtejc): an accepted index of myocardial performance that could be added to the diagnostic triage of ischaemia in the ER avoiding unnecessary admissions. We followed 85 patients presenting at the ER with acute chest pain. In 72 patients, negative ECG and myocardial enzyme dynamics ruled out coronary origin during the first 24 h after admission. In 8 of the 72 patients, coronary catheterisation found normal coronary arteries. In this group, average dP/dtejc was 163 (range 92-232). In 35 patients in whom the new non-invasive cardiac performance index dP/dtejc was above a threshold of >150, acute MI was ruled out. In 13 patients, acute chest pain had coronary origin confirmed by ECG and/or positive enzymes. The average dP/dtejc in this group was 117 (range 61-149). The dP/dtejc values were found to be significantly higher in patients without acute MI (p<0.001). Preliminary findings suggest that nearly 40% of patients presenting with acute chest pain could be spared the risks and costs of unnecessary hospital admission and more invasive cardiac testing by simply adding a easy to use, immediately obtained, test to the diagnostic protocol, and using a threshold of dP/dtejc>150 to rule out heart attack.

Exacerbation, then clearance, of mutation-proven Darier's disease of the skin after radiotherapy for bronchial carcinoma: a case of radiation-induced epidermal differentiation?

We investigated a radiotherapy-induced flare and subsequent clearance of skin lesions of a patient with the rare, dominantly inherited genodermatosis, Darier's disease (DD). The DD gene, ATP2A2, was recently isolated and shown to be a cation pump responsible for regulating intracellular calcium homeostasis. A severe exacerbation of Darier's skin lesions developed within the radiation field when 40 Gy of palliative thoracic external-beam radiation therapy and concurrent chemotherapy (cisplatin and hydroxyurea) were delivered for non-small cell lung cancer. The DD lesions subsequently completely cleared from irradiated skin, as they did when a subsequent course of radiation alone was given for a loco-regional tumor recurrence. The two radiation therapy-treated areas of skin remained free from lesions of the skin disorder until the patient's death from progressive lung cancer 9 months later. The nucleotide sequence of the patient's ATP2A2 gene was determined by PCR-based cycle sequencing. We identified four nucleotide sequence variants in the ATP2A2 gene in this patient. Three were probable polymorphisms and the other appeared to be a novel disease-causing mutation (R751Q), situated in the transmembrane portion of the ATP2A2 protein. This finding confirmed the clinical diagnosis. Since epidermis turns over every 3-4 weeks, total and persistent clearance of the DD lesions by chemoradiotherapy suggests that this treatment induced sustained differentiation of the DD-affected skin by an unknown mechanism. Oncologists treating malignant disease in patients with DD should anticipate temporary deterioration in DD-involved irradiated skin. Radiation therapy has therapeutic potential in severe DD.

Dynamics of kinks in one- and two-dimensional hyperbolic models with quasidiscrete nonlinearities.

We study the evolution of fronts in the Klein-Gordon equation when the nonlinear term is inhomogeneous. Extending previous works on homogeneous nonlinear terms, we describe the derivation of an equation governing the front motion, which is strongly nonlinear, and, for the two-dimensional case, generalizes the damped Born-Infeld equation. We study the motion of one- and two-dimensional fronts finding a much richer dynamics than in the homogeneous system case, leading, in most cases, to the stabilization of one phase inside the other. For a one-dimensional front, the function describing the inhomogeneity of the nonlinear term acts as a "potential function" for the motion of the front, i.e., a front initially placed between two of its local maxima asymptotically approaches the intervening minimum. Two-dimensional fronts, with radial symmetry and without dissipation can either shrink to a point in finite time, grow unboundedly, or their radius can oscillate, depending on the initial conditions. When dissipation effects are present, the oscillations either decay spirally or not depending on the value of the damping dissipation parameter. For fronts with a more general shape, we present numerical simulations showing the same behavior.

Bexarotene capsules and gel for previously treated patients with cutaneous T-cell lymphoma: results of the Australian patients treated on phase II trials.

Bexarotene (Targretin, LGD1069) is a novel synthetic retinoid analogue that binds selectively to retinoid X receptors. We describe eight previously treated patients who entered phase II international multicentre studies examining the role of bexarotene in cutaneous T-cell lymphoma. Patients received either the oral formulation (n = 7) or the topical gel (n = 1). Of the seven patients who received 300 mg/m2 per day capsules, five (71%) achieved a partial response, with mean time to onset of response of 27 days (range, 20-29) with responses persisting for a mean of 92 days (range, 57-115). The single patient receiving the topical preparation (stage IB) remains in partial response at 31 months. The major toxicity with oral administration was hypertriglyceridaemia requiring therapy. Bexarotene capsules and gel are active and generally well-tolerated agents in patients with cutaneous T-cell lymphoma and studies examining its role in previously untreated patients or as part of combination therapy are warranted.

Mycosis fungoides: an Australian experience.

Analysis was undertaken of 107 patients with mycosis fungoides who presented to St. Vincent's Hospital, Melbourne, during 1977-95. The mean age at diagnosis (55 years) was significantly older than the mean age of onset of symptoms (48 years). The mean duration of follow-up was 7.7 years. Urban residence was over-represented in this group of patients and in those with mycosis fungoides recorded at the State Cancer Registry. Eighty-four per cent were diagnosed at Stage I or II of the disease. Presentation with disease more advanced than Stage I was more likely to be found in males. Disease localized only to the trunk accounted for 45% of all patients. The mean number of biopsies prior to diagnosis was 1.4 but two-thirds were diagnosed at first biopsy. Almost 85% of patients had as their initial treatment either PUVA (44.9%), topical steroids (20.6%) or topical nitrogen mustard (18.7%) and 57% received only one or two treatment modalities during the period of the study. Stage at presentation was not related to the likelihood of clearance following treatment, recurrence, progression to a more advanced stage of disease or survival.

The ear-lobe sign: a helpful sign in facial contact dermatitis.

The ear-lobe sign is seen in those who develop contact dermatitis to a substance applied with one hand to the skin of the face and neck. On the ipsilateral side of the face the ear-lobe is spared whereas on the contralateral side the ear-lobe is involved. The sign manifests because of the unique combination of the anatomy of the hand and the sweeping movement the hand makes during application.

The use of Terson lens capsule forceps when performing punch biopsy of the skin.

When performing skin biopsy using the skin biopsy punch, it is recommended that Terson lens capsule forceps be used as an aid to avoid crush artefact. This is because secure yet gentle purchase of the specimen is allowed by a row of small inwardly directed tines that arise from the 2.5 mm horizontally placed grasping blades, which are inserted into the incision created by a 3 mm biopsy punch. The instrument also has the extra advantages of being in the correct working position when held with the hand in the resting position between prone and supine of allowing an uninterrupted line of vision to the wound during use and is of a shape that minimizes unintentional contact with tissue.

Scleredema of Buschke: a report of seven cases.

Scleredema of Buschke is an uncommon dermatosis characterized by thickened, indurated skin, sometimes with erythema. Histopathology shows thickened dermal collagen with a mild infiltrate of mucin in the deeper dermis. Seven adults with scleredema are presented, four females and three males, and their mean age at diagnosis was 54 years. All had diabetes mellitus for an average of 13 years prior to the onset of scleredema. Complications of diabetes, especially retinopathy (n = 5), neuropathy (n = 4) and peripheral vascular disease (n = 3), were present in five patients. One patient died (cause not established), and another has life-threatening cardiomyopathy. We have no evidence that the scleredema was a significant aetiologic factor in either case, despite published reports of fatalities related to scleredema. Three patients were followed up for more than 1 year and, irrespective of therapy, the scleredema did not resolve in any patient.

Psoriasis: changing clinical patterns.

Although psoriasis has been recognized at least since Biblical times new forms, associations and influences continue to be described in the twentieth century. New forms include the rupioid erythema annulare centrifugum-like and follicular patterns. Associations with vitiligo bullous pemphigoid and lupus erythematosus have been recently described. Endoscopic surgery has increased para umbilical psoriasis while Sun Smart campaign have reduced photo-aggravated psoriasis. Infections such as paediatric perianal streptococcal cellulitis and drugs including angiotensin converting enzyme inhibitors and cytokines exacerbate psoriasis.

Drug eruptions with lichenoid histology produced by captopril.

Three cases are presented with a rash due to captopril which, on histology, showed a lichenoid pattern of bandlike upper dermal infiltrate of lymphocytes and histiocytes, together with hydropic degeneration of the basal layer of the epidermis producing Civatte bodies and pigmentary incontinence. The rash presented either as a pityriasis rosea-like picture which appeared about three to six months after the onset of treatment in patients taking low doses, or alternatively, as lichenoid plaques which appeared three to six months after commencement of medication in patients taking high doses. Although both clinical patterns produced a "saw tooth" pattern of the epidermal rete ridges, hypergranulosis and acanthosis were seen only with the lichenoid plaques.

Conjunctival involvement with mycosis fungoides in a patient receiving PUVA therapy.

A 40-year-old woman had documented mycosis fungoides of the skin. Over a period of five years, she had undergone intermittent treatment with psoralen long-wave ultraviolet light (PUVA) therapy. Despite regression of the skin lesions, tumor plaques developed in her eyelid and conjunctiva within the area shielded by dark glasses. Light and electron microscopic examination of a biopsy from the conjunctival plaque confirmed that the lesion was a deposit of mycosis fungoides. Local radiotherapy resulted in complete regression of these ocular lesions. The conjunctiva may well be an iatrogenic "sanctuary site" when this disease is treated with PUVA therapy.