Bisphosphonate therapy for unresectable symptomatic benign bone tumors: a long-term prospective study of tolerance and efficacy.

OBJECTIVES: To evaluate the long-term tolerance of bisphosphonates proposed as an alternative therapeutic option for symptomatic unresectable benign bone tumors and to evaluate the long-term efficacy of this treatment. METHODS: From March 2007 to March 2011, patients with unresectable symptomatic benign bone tumors were consecutively included in this institutional review board-approved study and treated with bisphosphonates. Prospectively long-term follow-up is reported. The study endpoints were to describe the long-term tolerance, the clinical evolution of pain for each patient and the radiological success defined as a complete disappearance of inflammation and ossification of the bone lesion. All complications and side effects were recorded. RESULTS: Eight patients (mean age 16 years; range 7-42) with various tumor subtypes were included: aneurysmal bone cysts (N=5), Langerhans cell histiocytosis (N=1), osteoblastoma (N=1), and a giant cell tumor (N=1). Tumors were located in cervical (N=4) or thoracic (N=1) vertebrae, femoral shaft (N=1), acetabulum (N=1) and sacrum (N=1). Mean number of bisphosphonate cycles was 3 (range: 1-6) over a median period of 10 months. The median clinical and imaging follow-up period was 21 months (6 to 63 months). No severe complications due to treatment or lesion recurrence were reported. Pain disappeared within 6 weeks of the first cycle for all but one patient. Ossification of the bone lesion was observed for all patients but one, complete for two and partial for the five others. CONCLUSIONS: Bisphosphonates appear to be an effective option without adverse effects for the non-operative management of symptomatic benign bone tumors.

Peak anaerobic power in patients with COPD: gender related differences.

The aim of the study was to investigate peak anaerobic power during all-out exercise in patients with COPD. Twenty patients (ten women, ten men) [FEV1=50.5 (7.6)% of predicted] and 11 healthy subjects (six women, five men) performed: (1) three maximal sprints on a cycle ergometer to measure peak anaerobic power (Pmax) and optimal velocity (Vopt), (2) assessment of whole-body composition by dual-energy X-ray absorptiometry (DEXA) and (3) assessment of mean habitual daily energy expenditure (MHDEE). Pmax was 30% lower in COPD than in healthy subjects [22.9 (7.1) vs. 32.8 (5.6) W kg-1 (legs FFM), P<0.001]. Nevertheless, Vopt was similar in both series. In COPD, Pmax was lower in women than in men [21.4 (7.7) vs. 23.8(6.4) W kg-1 (legs FFM), P<0.05]. Vopt was lower in women than in COPD men [72.6 (11.3) vs. 89.3 (13.8) rpm, P<0.05]. MHDEE was lower in COPD than in healthy subjects [8019 (1254) vs. 9093 (1660) kJ day-1]. In COPD, MHDEE was lower in women than in men (P<0.001). This study demonstrates that in COPD patients, the decrease in peak anaerobic power could play a role in their specific muscular dysfunction. Considerable differences were observed in peripheral muscle function, body composition and MHDEE between women and men. The skeletal muscle of women and men may therefore adapt to COPD in different ways.

[Decrease of dynamic muscle function in patients with COPD: preliminary study]. / Diminution de la fonction musculaire dynamique dans la BPCO: étude préliminaire.

BACKGROUND: The aim of the study was to investigate dynamic muscle function during all-out exercise in patients with chronic obstructive pulmonary disease (COPD) and to observe the relationship between body composition and skeletal muscle function. MATERIAL AND METHODS: Eight patients (FEV1: 53.0 +/- 9.3%) performed three tests i) three maximal sprints on a specialised cycle ergometer to assess individual Velocity-Power relationship, and measure of maximal anaerobic power (Pmax), optimal velocity (Vopt), ii) assessment of whole-body and subregional fat-free mass (FFM) by dual-energy X-ray absorptiometry, iii) determination of maximal oxygen consumption. RESULTS: Maximal anaerobic power and corresponding optimal velocity were 3.9 +/- 1.6 W x kg(-1) et 85.4 +/- 17.0 rpm, respectively. COPD showed a 30% decrease of Pmax, compared to healthy older subjects (5.6 +/- 1.1 W x kg(-1)). No such difference was observed with Vopt (85.4 +/- 13.0 rpm vs 86.8 +/- 9.5 rpm). Pmax and Vopt were highly significantly correlated with lower extremities FFM, but not with airflow obstruction parameters. CONCLUSION: Our results showed that skeletal muscle function parameters such as Pmax and Vopt could characterise peripheral muscle weakness of COPD.

Prognostic score of short-term survival in HIV-infected patients admitted to medical intensive care units.

A retrospective cohort was set up to identify prognostic factors associated with in-hospital survival in HIV-infected patients admitted to medical intensive care units (MICUs), from 1991 to 1994. Survival from MICU admission to hospital discharge (or in-hospital fatal issue) was estimated and a prognostic score at MICU admission was developed. One hundred and thirty patients were recruited of whom 20% were AIDS-free prior to admission. In-hospital mortality rate was 65%. Median survival was 20 days. The following variables were predictive of mortality: Simplified Acute Physioloy Score II (SAPS II): (hazard ratio [HR]=1.5 for 10 points higher, P<10(-3)), time between HIV diagnosis and admission >5 years (HR=2.7, P<10(-4)), hypoalbuminaemia (HR=1.2 per 5 g/l lower, P=0.03). The prognostic score developed was: SAPS II+25 (if time between HIV diagnosis and MICU admission >5 years) albuminaemia (g/l). A new prognostic score including SAPS II, prior HIV history and albuminaemia better reflected the in-hospital mortality than SAPS II alone. Our findings may still be useful to better evaluate the immediate prognosis of current HIV-infected patients admitted to MICU, particularly those naive to antiretroviral therapy or in treatment failure.

[Acute adrenal insufficiency due to bilateral adrenal hematoma following severe thrombopenia induced by low-molecular-weight heparin]. / Insuffisance surrénalienne aiguë par hématome surrénalien bilatéral au décours d'une thrombopénie sévère induite par une héparine de bas poids moléculaire.

BACKGROUND: Bilateral adrenal hematoma is an uncommon cause of acute adrenal insufficiency. An association with thrombopenia induced by low-molecular-weight heparin even more so. Diagnosis is difficult as the clinical manifestations mimic septic shock. CASE REPORT: A 63-year-old woman developed acute adrenal insufficiency due to bilateral adrenal hematoma following severe thrombopenia induced by low-molecular-weight heparin prescribed after an orthopedic operation. Outcome was favorable. CONCLUSION: Acute adrenal insufficiency must be entertained as a possible diagnosis in patients with heparin-induced thrombopenia.

Non-fatal clozapine (LEPONEX) intoxication with toxicokinetic evaluation.

A 29-y-old male attempted suicide with 3000 mg clozapine, 150 mg zopiclone, alprazolam and unknown quantities of alcohol. He was admitted in a deep hypotonic coma with respiratory depression, inhalation pneumonia and vascular collapse. Symptomatic treatment involved mechanical ventilation, vascular filling and antibiotics. The patient was discharged from the Intensive Care Unit 72 h after the suicide attempt with no sequelae. To detect and quantify clozapine in plasma, high-pressure liquid chromatography showed a 4 h absorption phase and a peak serum concentration of 5200 ng/ml. Three successive elimination t1/2 values of 38, 24 and 13 h were calculated.

Anticholinergic versus beta 2-agonist on gas exchange in COPD: a comparative study in 15 patients.

beta-agonist bronchodilators are known to influence gas exchange and ventilation-perfusion relationships in asthmatic patients, where they induce hypoxaemia via hypoxic vasoconstriction. As this effect could have serious consequences in chronic obstructive pulmonary disease (COPD) patients with chronic hypoxaemia, alternative agents have been sought. It has been shown that inhaled anticholinergic drugs may be of value in this condition. In the present study, we compared the effects of salbutamol (Sb) and ipratropium bromide (IB) inhalation on gas exchange in 15 patients with stable COPD. All patients had a history of COPD (mean arterial oxygen tension (Pa,O2) = 8.2 +/- 1.0 kPa (61.8 +/- 7.3 mmHg) forced expiratory volume in one second (FEV1) = 39 +/- 12%; FEV1/vital capacity (VC) = 42 +/- 6%) and no evidence of acute respiratory failure. Haemodynamic and gas exchange data were recorded after right catheterization by the multiple inert gas elimination technique. Measurements were made under basal conditions, after two puffs of freon propellant (placebo) and after two puffs of either 200 micrograms Sb or 200 micrograms IB in a randomized design. Sb and IB reduced airway resistances to the same extent, but had no significant influence on the haemodynamic and ventilation parameters. There was a slight but significant decrease in arterial carbon dioxide tension (Pa,CO2) = 6.0 +/- 0.8 versus 6.4 +/- 0.8 kPa (45.4 +/- 5.9 versus 47.9 +/- 6.3 mmHg) p < 0.05 with an enhanced perfusion distribution heterogeneity and a slight improvement in ventilation homogeneity shown by a decrease of the decimal logarithm of SD of the ventilation distribution (LogSDV) after inhalation of IB relative to control. Since these alterations did not affect arterial oxygen tension we concluded that inhalation of these doses of salbutamol or ipratropium bromide do not affect gas exchange in patients with stable chronic obstructive pulmonary disease. The normal home treatment: inhalation of two puffs of these bronchodilating drugs thus appears to be safe. The choice of agent will depend on the extent of the bronchodilator effect in a given individual.

Effect of inhaled nitric oxide on hemodynamics and VA/Q inequalities in patients with chronic obstructive pulmonary disease.

Nitric oxide (NO) has been reported to be an endothelium-derived relaxing factor, and hypoxic pulmonary vasoconstriction seems to be enhanced by inhibitors of endothelially dependent vascular relaxation. We examined the circulatory effects of inhalation of 15 ppm NO in air in 14 hypoxic patients suffering from chronic obstructive pulmonary disease (COPD). Of these patients 4 breathed 100% O2 before NO. The effects of NO inhalation on pulmonary gas exchange were also studied in 12 of these patients using the multiple inert gas elimination technique, 3 of whom breathed air, 100% O2, and 15 ppm NO in air in succession. Under baseline conditions, both mean +/- SD pulmonary artery pressure and pulmonary vascular resistance were increased (Ppa = 24.3 +/- 10.4 mm Hg and PVR = 3.3 +/- 1.1 mm Hg/L/min, respectively). Although the pulmonary circulatory effects were not immediate, with no detectable changes after 1 min NO inhalation, Ppa and PVR fell significantly (-19.1 +/- 10.5%, p < 0.02 and -29.3 +/- 15.1%, p < 0.02, respectively) after 10 min NO inhalation. Moreover, the extent of the NO-induced reduction in Ppa was found to depend on the level of baseline pulmonary arterial hypertension. No systemic circulatory effects were observed. The mean VA/Q ratio and the dispersion of ventilation and blood flow distributions were not altered by NO inhalation, although there was a significantly higher percentage of ventilation (7.3 +/- 7.3%, p < 0.05) in poorly and unperfused areas (VA/Q > 10).(ABSTRACT TRUNCATED AT 250 WORDS)

Effects of inspiratory flow rate alterations on gas exchange during mechanical ventilation in normal lungs. Efficiency of end-inspiratory pause.

The influence of inspiratory flow rate (TI), without changing respiratory frequency, tidal volume, and FIO2, was investigated in 11 normal lungs in patients undergoing mechanical ventilation because of central respiratory failure due to stable coma. The patients were anesthetized and paralyzed. They first received a conventional ventilation (TI = 25 percent, pause = 10 percent) and then, were submitted to four different TI values, randomly administered without any end-inspiratory pause (EIP) (TI = 20 percent; TI = 33 percent; TI = 50 percent; TI = 67 percent). In the middle and at the end of the procedure, a return to basal conditions was introduced. At each ventilator setting, the following were obtained: respiratory flow (Pneumotachograph Fleish No. 2), airway pressure, FRC changes (inductive plethysmography), arterial and mixed venous blood gases, hemodynamic data, and VA/Q ratios distribution using multiple inert gases technique. EIP suppression provides a significant increase in VA/Q mismatch (until TI = 50 percent) and in shunt effect (between 3 and 9 percent of cardiac output [QT]). The absence of simultaneous PaO2 change is due to increasing PVO2 linked to a higher QT. The shorter the TI, the higher the PaCO2 connected with a relative alveolar hypoventilation. However, increasing TI without EIP significantly decreases ventilation distribution inequalities. This improvement is concomitant with a rise in FRC (FRC67-FRC20 = 0.340 +/- 0.450, p < 0.05) without any change in other variables or auto-PEEP production. In summary, in subjects with very slight mechanical lung impairment (peak inspiratory pressure = 20.5 +/- 5.3 cm H2O at TI = 20 percent and 15.2 +/- 3.3 cm H2O at TI = 67 percent), this study confirms the deleterious effect of EIP suppression and TI decrease. One can compensate for this effect of EIP absence by increasing TI as soon as it reaches TI = 67 percent, ie, inverse ratio ventilation.

[Ventricular arrhythmia and halofantrine intake. Probable deleterious effect. Apropos of 3 cases]. / Arythmies ventriculaires et prise d'halofantrine. Effet délétère probable. A propos de 3 observations.

Incidence and malignant forms of imported Plasmodium falciparum malaria are increasing, and chemoprevention is more and more replaced by stand-by treatment and radical cure in preventing access on return from malaria areas. Halofantrine is recommended for this radical cure: it's an habitually well-tolerated amino-alcohol with very few side-effects. We report three cases of long QT-interval due to halofantine: three different young women coming back from Africa took halofantrine (500 mg (2 tablets) six hourly for three doses on the first and the seventh day) and all presented with syncopal episodes. Serum electrolyte concentrations and echocardiograms were normal. In one case only, a diagnosis of Plasmodium falciparum malaria was made, without severe manifestations, and in the two other cases, treatment was a radical cure. In two cases, several bursts of torsades de pointes ventricular tachycardia due to halofantrine were proven and electrophysiological cardiac tests concluded that they had a congenital long QT-interval/Romano-Ward syndrome). So far halofantrine cardiac toxicity was unknown with single dose of 24 mg/kg/d. This phenomenon can be very severe in case of preexisting cardiopathy. In spite of the rarity on the congenital Romano-Ward syndrome, systematic electrocardiogram is necessary before giving halofantrine.