The new topical ascomycin derivative SDZ ASM 981 does not induce skin atrophy when applied to normal skin for 4 weeks: a randomized, double-blind controlled study.

BACKGROUND: SDZ ASM 981 is a selective inhibitor of inflammatory cytokines released from T lymphocytes and mast cells, which has been developed for the treatment of inflammatory skin diseases. OBJECTIVES: In the present study, the atrophogenic potential of SDZ ASM 981 1% cream in humans was compared with that of medium and highly potent topical steroids, and vehicle. METHODS: Four different preparations, SDZ ASM 981 1% cream, the corresponding vehicle of SDZ ASM 981 1% cream, betamethasone-17-valerate 0.1% cream and triamcinolone acetonide 0.1% cream, were applied to the volar aspect of the forearms of 16 healthy volunteers, twice daily, 6 days a week, for 4 weeks. Skin thickness was evaluated by ultrasound examination, clinical signs of atrophy by stereomicroscopy, and epidermal thickness was assessed by histology. RESULTS: Both topical corticosteroids induced a significant reduction in skin thickness, as compared with SDZ ASM 981 1% cream and vehicle, which were shown to be equivalent. The difference in skin thickness (measured by ultrasound examination) between patients treated with SDZ ASM 981 1% cream and those receiving either of the two topical steroids was significant from day 8 onwards. Histological analysis performed at day 29 showed significant epidermal thinning with topical steroids compared with SDZ ASM 981 1% cream or the vehicle. Conclusion The lack of atrophogenic properties of SDZ ASM 981 1% cream in this short-term study demonstrates its potential as long-term treatment for inflammatory skin diseases, thus overcoming a major drawback of topical steroids. This may also be important for the treatment of children, and sensitive areas of skin, such as the face and skin-folds.

Etude des marqueurs serologiques de l'hepatite B chez les patients congolais testes pour l'infection a VIH

334 prelevements ont ete realises dans le Service des Maladies Infectieuses de l'Hopital de Makelekele et testes en VIH et pour les marqueurs de l'hepatite B. Le but de l'etude etait de savoir s'il existait des liaisons significatives entre la presence des marqueurs de l'hepatite B et celui de l'infection a VIH. La majorite des patients; 286 de 334 patients (85;6 pour cent) etaient porteurs d'anticorps anti-HBc; ce qui prouve la frequence de l'infection VHB a Brazzaville. Mais on note que l'absence des marqueurs du virus de l'hepatite B etait liee avec l'absence de l'infection VIH (p=0;00003). La prevalence du portage de l'antigene HBs etait de 11;4 pour cent et les malades VIH negatifs etaient plus souvent porteurs de l'antigene HBs par rapport aux patients VIH positifs (16 vs 22; N.S.). L'antigene HBe etait plus souvent mis en evidence chez les patients co-infectes (HBV/VIH) que chez les patients infectes seulement par le virus de l'hepatite B (p=0;037)

[African histoplasmosis due to Histoplasma capsulatum var. duboisii: relationship with AIDS in recent Congolese cases]. / Histoplasmose africaine à Histoplasma capsulatum var. duboisii: liens avec le SIDA à propos de cas congolais récents.

Six new cases are described for African histoplasmosis, Histoplasma capsulatum var. duboisii, from Congo. The first was an HIV sero-negative child who has been monitored for the last three years. While under treatment with ketoconazole, amphotericin B, and finally itraconazole, the development of the infection was accompanied by purulent lesions, mainly cutaneous, but also superficial and deep lymphadenopathies. As a last option, itraconazole gave very satisfactory results both during the acute phase and during long-term treatment. However, eight months after treatment had ceased, there was a relapse and the long-term treatment had to be restarted. The other cases concerned HIV sero-positive patients with disseminated infections that had all been mistaken for tuberculosis. After diagnosis of the infection in two cases, the following two years of treatment could not prevent death. A fourth case, diagnosed in December 1994, is currently undergoing treatment. The fifth subject was lost after diagnosis during follow-up, but inquires made after the discovery of the patient's death strongly indicated acquired immunodeficiency as the cause. The last of these six cases, determined as HIV sero-negative, showed large bony lesions of the spinal column associated with a sore on the thorax. Thus, in a short period of time, three or four cases of African histoplasmosis occurred which were associated with HIV infection. Only seven identical observations have previously been reported in the literature. Therefore, we believe that this mycosis should now be included in the criteria for the diagnosis and definition of AIDS in the tropics.

PIP: In Congo, the parasitology-mycology laboratory in Brazzaville diagnosed six new cases of African histoplasmosis (Histoplasma capsulatum var. duboisii) in a 3-year period. Three cases had AIDS. Another case was strongly suspected of being HIV seropositive. The first case was a 4-year-old child from Brazzaville who had been monitored for more than 3 years. Health providers treated him first with ketoconazole, then amphotericin B, and finally itraconazole. The child's African histoplasmosis was characterized by purulent lesions, particularly cutaneous, but also superficial and deep lymphadenopathies. Itraconazole adequately treated the child's condition both during the acute phase and during long-term treatment. Eight months after the end of itraconazole treatment, the child suffered a relapse, resulting in re-administration of longterm treatment. The remaining African histoplasmosis cases had disseminated infections, which were initially suspected to be tuberculosis. After diagnosis, two cases died despite two years of treatment. The fourth case was diagnosed in December 1994 and is still receiving treatment. After diagnosis, the fifth case was lost to follow-up. Health providers later learned that AIDS was probably responsible for the patient's death. The sixth case did not have HIV infection. The 32-year-old man, a nurse in the central army hospital in Brazzaville, had large bony lesions of the spinal column associated with a sore on the thorax. The literature shows only seven other African histoplasmosis cases infected with HIV. These HIV-infected African histoplasmosis cases along with the seven cases in the literature suggest that African histoplasmosis should be included in the criteria for the diagnosis and definition of AIDS in tropical countries.

[TNF and sepsis]. / TNF et sepsis.

Recent experiments have demonstrated that TNF plays an important role in the pathogenesis of septic shock. To confirm the involvement of TNF in human septic shock, serum TNF levels were measured in 10 adult patients admitted to the intensive care unit for sepsis with or without shock. Septic shock was corroborated by hemodynamic data (right catheterization, measurement of cardiac output by thermodilution). For TNF measurement, venous blood samples were withdrawn, as soon as possible after the onset of sepsis, into a pyrogen--free tube. Serum TNF levels were determined using a radioimmunoenzymatic assay (IRE Medgenix). During septic shock (n = 7), TNF levels were significantly higher (m = 354 +/- 131 pg/ml) than during sepsis without shock (n = 8; m = 145 +/- 35 pg/ml) (p less than 0.0005). TNF levels were also significantly higher in non-survivors (m = 392 +/- 111 pg/ml) than in survivors (m = 167 +/- 81 pg/ml) (p less than 0.0005). The value of 250 pg/ml seems to be critical: no patient without shock had TNF levels above 250 and all the patients who died early during the first 24 h) had TNF levels above 250. The TNF level is negatively correlated with the platelet count (r = -0.70; p less than 0.05). These data favor a pathophysiological for TNF in human sepsis and septic shock.

[Pseudosurgical acute abdomen syndrome in primary pulmonary hypertension]. / Syndrome douloureux abdominal pseudochirurgical lors d'une hypertension artérielle pulmonaire primitive.

The case is reported of a 49-year-old chronic alcoholic woman, who presented with severe pulmonary arterial hypertension (PAH) mimicking as an acute abdomen. She was admitted with right-sided hypochondrial abdominal pain and hepatomegaly, with a moderate jaundice. On admission to intensive care unit, she had an arterial blood pressure of 110/70 mmHg, a heart rate of 100 b.min-1, and a respiratory rate of 36 c.min-1. An electrocardiogram showed sinus rhythm and right-sided heart failure. Whilst breathing 6 l.min-1 oxygen, her arterial blood gases were: PaO2 47 mmHg PaCO2 29 mmHg. Severe PAH was confirmed by measuring her mean pulmonary arterial pressure, which was 46 mmHg, whilst her pulmonary wedge pressure was 7 mmHg. Hepatic function was also altered: total bilirubin 41 mumol.l-1, alkaline phosphatase 145 UI.l-1 and gamma glutamyl transferase 1 340 UI.l-1. She developed arterial hypotension, which did not respond to increasing doses of isoproterenol. She died on the third day. Necropsy confirmed the diagnosis of primary PAH, with acute "cardiac liver".

[Hemodynamic and respiratory effects of enoximone in acute respiratory insufficiency of chronic obstructive bronchopneumopathy]. / Retentissement hémodynamique et respiratoire de l'enoximone au cours de l'insuffisance respiratoire aiguë des bronchopneumopathies chroniques obstructives.

Hemodynamic effects and gas exchange were studied in twenty COPD patients undergoing mechanical ventilation before and 30 and 60 minutes after an intravenous administration of 1 mg/kg enoximone. Enoximone decreased significantly pulmonary arterial pressure and pulmonary vascular resistances without significantly decrease of systemic vascular resistances 60 minutes after a slight dose of 1 mg/kg. Right ventricular ejection fraction increased; O2 arterial pressure, CO2 arterial pressure, intrapulmonary shunt remained unchanged. We concluded that enoximone induced pulmonary vasodilation in patients with decompensated COPD and increased right ventricular function without deleterious effects in gas exchange.

Respiratory and hemodynamic effects of halothane in status asthmaticus.

The respiratory and hemodynamic effects of halothane in patients with status asthmaticus who required mechanical ventilation was evaluated. Halothane was administered in 12 patients in a concentration of 1% for thirty minutes. Standard drug treatments and ventilator settings were not modified during halothane administration. The following data were collected before and after halothane administration: arterial blood gases, peak inspiratory pressure, VD/VT, pulmonary arterial pressure, right heart pressures and cardiac index (by means of the thermodilution method). After halothane treatment PaCO2 significantly decreased, arterial pH increased, peak inspiratory pressure decreased and VD/VT decreased significantly. Mean pulmonary arterial pressure and right heart pressures decreased and the cardiac index was unchanged. The heart rate significantly decreased and arrhythmias did not occur during halothane administration. The administration of halothane in patients with status asthmaticus requiring mechanical ventilation produces a rapid reduction in bronchospasm and barotraumatic injury and a rapid improvement in arterial blood gases, without any adverse hemodynamic effects.

[Nosocomial bronchopneumopathies]. / Bronchopneumopathies nosocomiales.

Nosocomial bronchopulmonary infections are common and severe complications, particularly in intensive care units. The high incidence of pneumonia is related to multiple factors such as underlying disease, acute respiratory failure, nutritional disorders, depressed mental status and the frequent need tracheal intubation. The most frequent cause of respiratory tract infection is aspiration of oropharyngeal secretions. In hospitalized patients, there is usually an oropharyngeal colonization with Gram-negative bacteria. Prevention of nosocomial bronchopulmonary infections requires close attention to the patient's environment, proper techniques, handwashing and decontamination of respiratory equipment.