Concomitant traumas influence prognosis in melanomas of the nail apparatus.

BACKGROUND: In nail apparatus melanomas (NAM), the role of standard melanoma prognostic factors is under discussion. The prognostic influence of traumas to the clinically apparent tumour has not been sufficiently examined. OBJECTIVES: To estimate the influence of traumas against the background of standard prognostic factors on the course of NAM. METHODS: In 33 patients (20 women, 13 men, median age 65.0 years) with NAM (median tumour thickness 3.5 mm), we retrospectively examined a detailed history of trauma to the affected extremity at first presentation. Histological or other standard prognostic factors and follow-up were studied prospectively using a standardized protocol. RESULTS: Of 33 patients, 21 had suffered injury to the clinically apparent melanoma primary between 4 and 72 months prior to definitive surgical treatment (diagnostic biopsy up to 3 months ahead of excision of the melanoma was not considered). Eight of these patients had undergone inadequate therapy procedures. In Kaplan-Meier analysis, trauma to the clinically apparent tumour and tumour thickness were found to be significant prognostic factors for recurrence-free survival, and trauma to the clinically apparent tumour, Clark level and tumour thickness were significant prognosis predictors for overall survival. In Cox's proportional hazards model, trauma to the clinically apparent tumour was found to be a significant and independent risk factor with regard to overall survival (hazard ratio 5.39; P = 0.029). An influence of trauma on the primary pathogenesis of NAM could not be confirmed. Only three patients reported trauma prior to the onset of tumour. CONCLUSIONS: From our data, trauma to the clinically apparent tumour might be a considerable risk factor in NAM. The diagnosis of NAM should be considered in lesions of the nail apparatus and further deterioration of the prognosis due to inadequate therapeutic attempts or injury to the NAM should be avoided.

[Sporotrichoid atypical mycobacterial infections. Antibiotic monotherapy]. / Sporotrichoide atypische Mykobakterien. Antibiotische Monotherapie.

Sporotrichoid forms of atypical mycobacterial infections usually do not show a tendency to spontaneous healing. The therapy of choice in such cases is systemic antibiotics. We report three cases of sporotrichoid atypical mycobacterial infections of the skin which healed completely under long-term monotherapy with modern antibiotics (levofloxacin, clarithromycin, minocycline). We recommend confirming the diagnosis by means of culture, followed by monotherapy with low side-effect antibiotics, based on sensitivity studies. If pathogen proof is obtained by PCR, antibiotic therapy should be based on the known sensitivity of the pathogen in question.

[American cutaneous leishmaniasis: special features in diagnosis and therapy]. / Kutane amerikanische Leishmaniose - Besonderheiten der Diagnostik und Therapie -

HISTORY AND CLINICAL FINDINGS: Three weeks after returning from a trip to Guatemala, a 33-year-old man developed two ulcers with indurated edges on his right leg and painful lymph nodes in the right groin. His general condition was not impaired. EXAMINATIONS: Histological examination revealed cellular infiltrates of the corium by lymphocytes and plasma cells, always accompanied by epithelial cells and multinuclear giant cells. Special stainings were unable to detect pathogens but Leishmania brasiliensis was identified using PCR. The Leishmania culture remained negative. THERAPY AND COURSE: After 7-day intravenous therapy with 20 mg/kg/d pentostam (pentavalent antimonial compound), the patient developed gastrointestinal complaints, coupled with a marked elevation of transaminases. Therapy was discontinued until the transaminase values normalized, then continued in reduced dosage (12 mg/kg body weight) for 23 days. The ulcers and lymphadenitis healed under this therapy. CONCLUSION: The diagnosis of American cutaneous Leishmaniasis may be complicated by the relative lack of pathogens in the lesions. PCR diagnosis are very helpful here. The therapy must be systemic owing to the danger of progression to mucocutaneous Leishmaniasis. The standard therapeutic pentostam has, however, a high rate of side effects and administration is exclusively intravenous.

[Arteriovenous fistula: an uncommon cause of leg ulcers]. / Arteriovenöse Fistel als seltene Ursache eines Ulcus cruris.

A 69-year-old woman presented with a therapy-resistant ulcer on the medial aspect of her left ankle present for 2 years. Previously there had been a blood vessel tumor at the same site, but it had regressed almost completely in adolescence following a bacterial infection. A whirring flow sound was e heard over the ulcer. Numerous arteriovenous connections in the area of the ulcer were shown in the form of vascular convolutions with duplex sonography and angiography. The diagnosis of arteriovenous fistula was made. In addition, there was calcinosis around the ulcer. Successful therapy consisted of excision of the ulcer and the underlying calcinosis, and of ligature of the multiple arteriovenous connections. Our patient demonstrates that smaller arteriovenous fistulas may exist for decades without symptoms. The classification, clinical patterns, diagnostic approach, possible complications (bleeding, ulceration) and therapy of the rare arteriovenous fistulas are discussed.

Cutis marmorata telangiectatica congenita: laser doppler fluxmetry evidence for a functional nervous defect.

We report a 5-month-old infant with cutis marmorata telangiectatica congenita (CMTC) without associated abnormalities and unusual hemicorporal vascular markings. Laser Doppler fluxmetry of the involved skin, carried out for the first time, and the measurement of the transcutaneous partial pressure of oxygen indicate a functional disturbance, which may be the expression of an alpha-adrenergic innervation deficit of the cutaneous terminal blood vessels.

Dapsone in rosacea fulminans.

Rosacea fulminans is a rare disease with female predominance characterized by abrupt onset of pustules, papules, and confluent nodules on the face. The conventional treatment consists of systemic glucocorticoids and isotretinoin. We present the case of a 56-year-old woman with a marked facial papulopustular eruption that had followed an initial period of severe seborrhoea. Conventional treatment produced no clear improvement. Dapsone treatment achieved complete healing in 5 weeks.

Herpes zoster in breast cancer patients after radiotherapy.

PURPOSE: We have studied the incidence of herpes zoster in patients with adjuvant radiotherapy for breast cancer with special emphasis on possible correlations with other prognostic factors or survival. PATIENTS AND METHODS: From 1/1985 through 12/1993, 1,155 breast cancer patients received postoperative radiotherapy with curative intent in our department. After mastectomy 961 patients were irradiated and after breast-preserving treatment 194 patients. The age ranged from 34 to 79 years, the median follow-up was 3.1 years (range: 0.3 to 12.4 years). There were 443 women (38%) pre- and 712 (62%) postmenopausal. 21% had T3- to T4-tumors, 55% had axillary lymph node involvement, and 65% received additional systemic hormonal and/or cytotoxic therapy. In case of postmastectomy radiotherapy, the lateral chest wall and lymphatics (axilla, parasternal and supraclavicular nodes) were irradiated with an anterior photon field to 50 Gy (axilla 44 Gy) and most of the chest wall with an electron field to 44 Gy in 2-Gy fractions. After breast-preservation, the breast was irradiated via tangential fields with 6- to 8-MV photons up to 50 Gy plus 8 Gy electron boost to the tumor bed. Most of the patients were followed routinely in the department for 2 to 5 years. The frequency of zoster was determined retrospectively by reviewing the patients' records. RESULTS: A zoster after radiotherapy occurred in 41/1,155 patients (3.7%), mostly within the first 2 years after completion of radiotherapy. All infections remained localized and there was no evidence for systemic infections. Type of treatment (mastectomy vs breast-preservation) had no impact on the frequency of herpes zoster (36/961 patients after mastectomy and 5/194 patients after breast-preservation). There was also no correlation with other prognostic factors such as age, menopausal status, stage of disease or the use of adjuvant chemotherapy, nor was the occurrence of zoster linked to the degree of acute skin reaction in the radiation field. Moreover, patients with zoster had the same prognosis as compared to patients without zoster with regard to local control and survival. CONCLUSIONS: The observed frequency of zoster (about 4% of patients after postoperative radiotherapy) in this retrospective study suggests that the risk of developing zoster in this patient group may be 3- to 5-fold higher as compared to the incidence in the general population. However, the occurrence of zoster was not linked to prognosis and treatment response.

[Radiation-induced morphea]. / Radiogene Morphaea.

Although the aetiology of morphea often remains unknown, various precipitating causes have been identified. Morphea is a rare development following irradiation. We observed a circumscribed scleroderma 14 years after x-ray-radiotherapy following surgery of breast cancer. Furthermore multiple weeping papules occurred within the radiation area. A relapse of the breast cancer was ruled out by histological examination which displayed a transepidermal elimination of acid mucin. The irradiation had obviously induced different reactions of the dermal fibroblasts (radiodermatitis, morphea, mucin production).

Pharmacological actions of SDZ 218-135, a novel positive inotropic agent.

The effects of the new inotropic agent, SDZ 218-135 [(+)-(S)-4-[3-(4-diphenyl-methyl-1-piperazinyl)-2-hydroxy-propyl]- 6-(2-hydroxyethyl)-5-methyl-1,2,4-triazolo-[1,5-a]pyrimidin-7(4H)-one], were investigated using in vitro and in vivo techniques. In isolated rat atria, SDZ 218-135 elicited a dose-dependent increase in contractile force (+50% at 10 microM), which was paralleled by an increase in functional refractory period. In anesthetized rats SDZ 218-135 enhanced left ventricular (+)dP/dtmax by 100% at 10 mg/kg without influencing heart rate, arterial blood pressure, and cardiac output. In contrast to its predecessor, DPI 201-106, cardiac relaxation remained essentially unimpaired. The positive inotropic action was also maintained in a rabbit model of depressed heart function after myocardial infarction, where SDZ 218-135 increased peak acceleration of blood in the aorta. The prolongation of the effective refractory period in rat atria suggested possible antiarrhythmic effects. Indeed, SDZ 218-135 showed a dose-dependent marked reduction in reperfusion arrhythmias after coronary artery occlusion in rats. This effect was most likely due to a Class III action, since SDZ 218-135 significantly increased action potential duration (+10% at 10 microM/l) of the isolated guinea pig papillary muscle. In conclusion, SDZ 218-135 is a novel positive inotropic agent with an interesting profile of action. It does not impair cardiac relaxation and shows antiarrhythmic effects in a model of reperfusion-induced arrhythmias. The in vivo and in vitro data are consistent with a mechanism of action via sodium channel agonism.

Pharmacological actions of DPN 205-734, a novel cardiotonic agent.

DPN 205-734 [5-(4-cyanophenyl)-1,2-dihydro-6-methyl-2-oxopyridin-3-carbo nitrile] was investigated in vitro in Langendorff rabbit hearts, guinea pig and rabbit papillary muscles, and rat myocardium and in vivo in anesthetized and unanesthetized dogs, pithed open-chest cats, anesthetized rats, and cardiomyopathic hamsters. In vitro, this substance caused a concentration-dependent positive inotropic effect. Left ventricular dP/dtmax was increased in anesthetized dogs after intravenous injection of 0.02 and 0.2 mg/kg (35 +/- 10 and 130 +/- 13%, respectively) and in unanesthetized dogs after oral doses of 0.05-0.5 mg/kg (15 +/- 2 to 71 +/- 14%). DPN 205-734 lowered blood pressure and total peripheral resistance in several experimental models, indicating an afterload-reducing effect. It induced moderate tachycardia. The positive inotropic effect is not explainable by beta-stimulation as shown in pithed open-chest cats pretreated with propranolol. A phosphodiesterase-inhibiting activity (IC50 = 35.5 microM), measured in rat myocardium, may be primarily responsible for the positive inotropic action. In guinea pig papillary muscles partially depolarized with 22 mM K+, DPN 205-734 in a concentration of 1 microM restored slow action potentials, which were then blocked by carbachol. These actions can be explained by the increase in cardiac cyclic AMP level due to a phosphodiesterase-inhibiting effect. In rabbit papillary muscles the positive inotropic effect of DPN 205-734 (100 microM) was only moderately inhibited by carbachol (3 microM), suggesting an additional mechanism.

Pharmacological actions of APP 201-533, a novel cardiotonic agent.

APP 201-533 [3-amino-6-methyl-5-phenyl-2(1H)-pyridinone] was investigated in vivo in anesthetized and unanesthetized dogs and pithed open-chest cats and in vitro in guinea pig atria and papillary muscles, skinned muscle fibers from pig hearts, and rat myocardium. Left ventricular dP/dt was increased in anesthetized dogs after intravenous injection of 0.2 and 2 mg/kg APP 201-533 (34 +/- 3 and 132 +/- 28%, respectively) and in unanesthetized dogs after oral doses of 1.5-7.5 mg/kg (34 +/- 11-138 +/- 43%). The substance induced moderate tachycardia. Large intraduodenal doses of APP 201-533 reduced afterload in anesthetized dogs. The compound does not seem to act either by stimulation of alpha- or beta-adrenoceptors or histamine receptors or by liberation of catecholamines. APP 201-533 up to 10(-5) M had no electrophysiological effect on normal action potentials in guinea pig papillary muscles. A phosphodiesterase-inhibiting activity (IC50 = 1.6 X 10(-4) M) may be responsible for the positive inotropic action. Another key to the mechanism of action may be based on our observation of a shift of the relationship between cardiac force and intracellular Ca2+ concentration. In contrast to amrinone and ouabain, APP 201-533 increases Ca2+ sensitivity of the myocardial contractile structures.

Positive inotropic and electrophysiological effects of APP 201-533 can be explained by an increase of cardiac cyclic AMP.

The possible mechanism of action of the positive inotropic agent APP 201-533 [3-amino-6-methyl-5-phenyl-2(1H)-pyridinone] was investigated. In guinea pig papillary muscles, APP 201-533 increased force of contraction concentration dependently at 10(-4)-10(-3) M. The effect was associated with an abbreviation of contraction and relaxation time. In guinea pig papillary muscles partially depolarized with 22 mM K+, APP 201-533 in concentrations of 10(-4) and 10(-5) M restored slow action potentials, which were not influenced by cimetidine, propranolol, and prazosin but were blocked by the Ca2+ antagonist PY 108-068 and by carbachol in an atropine-sensitive manner. The concentration-effect curve of histamine was shifted to the left in the presence of APP 201-533. These actions can be explained by the increase in cardiac cyclic AMP level that was found in rabbit papillary muscles and guinea pig left atria treated with APP 201-533 due to the known phosphodiesterase inhibitory effect of pyridinones. APP 201-533 increased the inotropic potency of dihydroouabain in guinea pig papillary muscles. It seems possible that this effect is based on an increased Ca2+ sensitivity of myocardial contractile structures as described previously for APP 201-533.