Wegener's granulomatosis: description of a case where cutaneous involvement was correlated with elevation of the c-ANCA titer.

Wegener's granulomatosis is a systemic disease characterized by necrotizing granulomas and vasculitis involving the upper and lower respiratory tract as well as the kidneys. Cutaneous manifestations consist mainly of papules or papulonecrotic lesions. c-ANCA are known to be a valuable adjunct for the diagnosis and follow-up of Wegener's granulomatosis with systemic involvement. We report the case of a 49-year-old man with Wegener's granulomatosis who developed two relapses of the disease with cutaneous manifestation and who presented with concomitant elevation of the c-ANCA and more precisely the subset PR3-ANCA during the acute phase of the disease.

Induction of cell cycle-dependent cytotoxicity and apoptosis by new heterodinucleoside phosphate dimers of 5-fluorodeoxyuridine in PC-3 human prostate cancer cells.

Fluorodeoxyuridine (5-FdUrd) is an antineoplastic agent with clinical activity against different types of solid tumours. To enhance the effectiveness of this drug, we have synthesised new heterodinucleoside phosphate dimers of 5-FdUrd. These dimers were compared to 5-FdUrd for their cytotoxic effect and the cell cycle dependence of cytotoxicity, as well as for their capacity to induce apoptosis and inhibit thymidylate synthetase (TS) in androgen-independent human PC-3 prostate tumour cells. Incubation of the cells with the dimers N(4)-palmitoyl-2'-deoxycytidylyl-(3'-->5')-5-fluoro-2'-deoxyuri din e (dCpam-5-FdUrd) and 2'-deoxy-5-flourouridylyl-(3'-->5')-2'-deoxy-5-fluoro-N(4)-octa decylc ytidine (5-FdUrd-5-FdC18) resulted in a marked cytotoxicity with IC(50) values of 4 microM, similar to 5-FdUrd. In contrast to 5-FdUrd, 100% toxicity was achieved with concentrations of 100-200 microM 5-FdUrd-5-FdC18. Flow cytometric analysis revealed an increase in the cell population in S-phase after treatment with 5-FdUrd, 5-FdUrd-5-FdC18, and dCpam-5-FdUrd from 36 to 63%, 50%, and 77%, respectively. dCpam-5-FdUrd was more potent than 5-FdUrd in arresting the cell cycle. Significant S-phase arrest was indicated by a decreased proportion of cells in G1- and G2/M-phases. Cell cycle arrest and inhibition of cell proliferation were followed by apoptosis, as shown by a 6- to 8-fold increased binding of Apo2.7 antibody, a 9- to 11-fold increase in caspase-3 activity, DNA fragmentation, and by cell morphology showing the appearance of apoptotic bodies. Importantly, 5-FdUrd-5-FdC18 increased the number of apoptotic cells to 160% compared to 5-FdUrd under the same conditions. As with 5-FdUrd, the two dimers also inhibited TS in a time- and concentration-dependent manner, although requiring 100-fold higher concentrations. In conclusion, dCpam-5-FdUrd and 5-FdUrd-5-FdC18 exert stronger cytotoxicity and induce more S-phase arrest and apoptosis than does 5-FdUrd in PC-3 cells, suggesting their potential role in the treatment of human prostate cancer.

Improving regulation of mean arterial blood pressure during anesthesia through estimates of surgery effects.

In this paper, a scheme for improvement of the regulation of mean arterial blood pressure (MAP) during anesthesia based on model predictive control (MPC) and estimates of the effects of disturbances (surgical events) is proposed. A linear model for the combined effects of surgical stimulations and volatile anesthetics on MAP is derived from experimental data. Based on it the potential improvement in blood pressure regulation is evaluated via a simulation study. The simulation study shows that when information about the effect of the surgical events on MAP is utilized by the controller maximum MAP deviations can be reduced by as much as 50% even when this information is inaccurate. At worst, (highly inaccurate information) no improvement is obtained.

Bullosis diabeticorum in a newly discovered type 2 diabetes mellitus.

Bullosis diabeticorum (BD), although a rare manifestation, is characteristic of diabetes mellitus. The exact origin of BD is unknown. We report another case of a 54-year-old man who developed a blistering lesion on his left leg. Histopathological examination revealed a microangiopathy with hyalinosis of the blood vessel walls.

[Erythema migrans with multiple lesions]. / Erythème chronique migrant avec lésions multiples.

INTRODUCTION: Erythema migrans with multiple lesions is observed in Europe in only 5-20 p. 100 of Borrelia infections. The number of lesions observed simultaneously in one patient is less than 7, considering all the cases published in the literature to date. CASE REPORTS: We report three patients who presented multiple macular, erythematous and centrifugal lesions localized on the trunk and the limbs. The first patient presented about thirty lesions, the second more than seventy, and the third about twenty. Serology investigation and immunoblots allowed to establish the diagnosis of a recent Borrelia Burgdorferi infection, with multiples lesions of erythema migrans. PCR performed on a skin biopsy of one of the patients confirmed the presence of Borrelia burgdorferi. Response to antibiotic therapy was immediate in all 3 patients. DISCUSSION: These 3 cases are of particular interest because the number of simultaneous lesions is much higher than what is reported in the European literature. These observations remind the clinician that the diagnosis of erythema migrans with multiple lesions should be included, in Europe as well, in the differential diagnosis of multiple annular dermatoses.

Model-based automatic feedback control versus human control of end-tidal isoflurane concentration using low-flow anaesthesia.

We studied the clinical use of an automatic feedback control system to adjust the end-tidal anaesthetic concentration with a low-flow method. The end-tidal controller uses two input signals (the end-tidal and inspiratory concentrations) to control the isoflurane concentration in the fresh gas flow, using a model-based algorithm. We studied 22 ASA I-III patients during elective surgery lasting more than 2 h. The anaesthetist was asked to make four step changes of the target end-tidal concentration (+0.3, +0.6, -0.3, -0.6 vol%), either manually (Group A) or by setting the target value for the feedback controller (Group B), and then the control was changed and the step changes were repeated, in a crossover design. Eighty step changes with each control method were compared in terms of response time, maximal overshoot and stability. The automatic control system was more accurate and stable than the human controller for step increases and step decreases, with less overshoot/undershoot and greater stability [e.g. maximal overshoot 14.7 (SD 3.7)% and 18 (8.1)% respectively for +0.6 vol% step changes, and 19.8 (3.7)% and 30.7 (13.2)% respectively for +0.3 vol% step changes]. However, the automatic control system showed a faster response time than the manual method only with large increasing steps (e.g. 149 (32) s and 205 (57) s respectively for +0.6 vol% step changes) and was not different from manual control for decreasing steps. Automatic control of the end-tidal isoflurane concentration can be better than human control in a clinical setting, and this task could be done automatically.

Monosymptomatic Loa loa infection.

We report the case of a 17-year-old student from Cameroon who presented an atypical, mono-symptomatic form of Loa loa infection, characterized only by rare subcutaneous movements of adult worms.

Fuzzy logic control of mechanical ventilation during anaesthesia.

We have examined a new approach, using fuzzy logic, to the closed-loop feedback control of mechanical ventilation during general anaesthesia. This control system automatically adjusts ventilatory frequency (f) and tidal volume (VT) in order to achieve and maintain the end-tidal carbon dioxide fraction (FE'CO2) at a desired level (set-point). The controller attempts to minimize the deviation of both f and VT per kg body weight from 10 bpm and 10 ml kg-1, respectively, and to maintain the plateau airway pressure within suitable limits. In 30 patients, undergoing various surgical procedures, the fuzzy control mode was compared with human ventilation control. For a set-point of FE'CO2 = 4.5 vol% and during measurement periods of 20 min, accuracy, stability and breathing pattern did not differ significantly between fuzzy logic and manual ventilation control. After step-changes in the set-point of FE'CO2 from 4.5 to 5.5 vol% and vice versa, overshoot and rise time did not differ significantly between the two control modes. We conclude that to achieve and maintain a desired FE'CO2 during routine anaesthesia, fuzzy logic feedback control of mechanical ventilation is a reliable and safe mode of control.

Fuzzy logic control of inspired isoflurane and oxygen concentrations using minimal flow anaesthesia.

In order to evaluate the performance of feedback fuzzy logic control of inspired oxygen and isoflurane concentrations, we studied 30 patients undergoing discectomy for lumbar (n = 26) or cervical (n = 4) disc herniation. Patients were allocated random to one of two groups: a standard group (n = 15) with low flow anaesthesia (1.2-1.3 litre min-1) and manual control of gas concentrations; and a fuzzy group (n = 15) with minimal flow (0.5 litre min-1) and fuzzy logic feedback control of gas concentrations. Fuzzy logic control achieved and maintained very accurately the desired isoflurane concentration. Oxygen concentration was controlled more precisely than in the standard group. Delivery and costs of oxygen and nitrous oxide were significantly lower in the fuzzy group (P < 0.01). Accumulation of foreign gases was observed in one patient during low flow and in 11 patients during minimal flow anaesthesia. In conclusion, fuzzy logic control of inspired oxygen and isoflurane concentration during minimal flow anaesthesia was reliable and reduced anaesthetic gas delivery and costs.