Voriconazole for chronic pulmonary aspergillosis: a prospective multicenter trial.

Early evidence suggests the efficacy of voriconazole for chronic pulmonary aspergillosis (CPA). We conducted a prospective, open, multicenter trial to evaluate the efficacy and safety of voriconazole for proven CPA in minimally or non-immunocompromised patients. Patients had CPA confirmed by chest computed tomography (CT) and/or endoscopy, positive Aspergillus culture from a respiratory sample, and positive serologic test for Aspergillus precipitins. Patients received voriconazole (200 mg twice daily) for a period of 6-12 months and were followed for 6 months after the end of therapy (EOT). The primary endpoint was global success at 6 months, defined as complete or partial (≥50 % improvement) radiological response and mycological eradication. Forty-one patients with confirmed CPA were enrolled. All patients had A. fumigatus as the etiologic agent. By EOT, five patients had died from comorbidities and seven had discontinued voriconazole due to toxicity. The global success rate at 6 months was 13/41 (32 %): 10/19 (53 %) for chronic necrotizing aspergillosis and 3/22 (14 %) for chronic cavitary aspergillosis (p = 0.01). The respective success rates at EOT were 58 and 32 %. Clinical symptoms and quality of life also improved during treatment. Voriconazole is effective for CPA, with acceptable toxicity. The response rate is higher and obtained more rapidly in necrotizing than cavitary forms.

The pharmacokinetics of lignocaine and beta-adrenoceptor antagonists in patients with acute myocardial infarction.

Lignocaine (lidocaine) and beta-adrenoceptor antagonists are widely used after acute myocardial infarction. The therapeutic value of these agents depends on the achievement and maintenance of safe and effective plasma concentrations. Lignocaine pharmacokinetics after acute myocardial infarction (MI) are controlled by a number of variables. The single most important is left ventricular function, which affects both volume of distribution and plasma clearance. Other major factors include bodyweight, age, hepatic function, the presence of obesity, and concomitant drug therapy. Lignocaine is extensively bound to alpha 1-acid glycoprotein, a plasma protein which is also an acute phase reactant. Increases in alpha 1-acid glycoprotein concentration occur after an acute MI, decreasing the free fraction of lignocaine in the plasma and consequently decreasing total plasma lignocaine clearance without altering the clearance of non-protein-bound lignocaine. Complex changes in lignocaine disposition occur with long term infusions, and therefore early discontinuation of lignocaine infusions (within 24 hours) should be undertaken whenever possible. Because the risk of ventricular tachyarrhythmia declines rapidly after the onset of an acute MI, lignocaine therapy can be rationally discontinued within 24 hours in most patients. Lignocaine has a narrow toxic/therapeutic index, so that pharmacokinetic factors are critical in dose selection. In contrast, beta-adrenoceptor antagonists' adverse effects are more related to the presence of predisposing conditions (such as asthma, heart failure, bradyarrhythmias, etc.) than to plasma concentration. The pharmacokinetics of beta-adrenoceptor antagonists are important to help assure therapeutic efficacy, to provide information about the anticipated time course of drug action, and to predict the possible role of ancillary drug effects (such as direct membrane action) and loss of cardioselectivity. Lipid solubility is the main determinant of the pharmacokinetic properties of a beta-adrenoceptor antagonist. Lipid-soluble agents like propranolol and metoprolol are well absorbed orally, and undergo rapid hepatic metabolism, with important presystemic clearance and a short plasma half-life. Water-soluble drugs like sotalol, atenolol, and nadolol are less well absorbed, and are eliminated more slowly by renal excretion. Clinical assessment of beta-adrenoceptor antagonism is more valuable than plasma concentration determinations in evaluating the adequacy of the dose of a particular beta-adrenoceptor antagonist.(ABSTRACT TRUNCATED AT 400 WORDS)

Prognostic impact of cathepsin D and c-erbB-2 oncoprotein in a subgroup of node-negative breast cancer patients with low histological grade tumors.

Some node-negative breast cancer patients, with initially good prognosis, relapse from their cancer and are poorly identified. In the present study, based on prospective data of 197 tumors, we measured cathepsin D (cath D, n=197), pS2 protein (n=125), c-erbB-2 oncoprotein (n=100) and epidermal growth factor receptor (EGF-R, n=99) to better define the risk of relapse of node-negative patients in comparison with that defined by the clinical and histological factors. The median follow-up in surviving patients was 75 months. Univariate analysis indicated that patients with histological grade III tumors (the Scarff, Bloom and Richardson classification) had a much poorer prognosis than those with histological grade I or II tumors (P=0.0027 for relapse-free survival and P=0.0156 for overall survival). When the population of node-negative patients was divided by tertiles, high cath D levels showed a significant association with an early relapse (P=0.0316). Using cut-off values, patients with high cath D (> or =25 pmol/mg protein) or c-erbB-2 oncoprotein (> or =4 Human Neu Unit/microg protein) levels, had a significant worse relapse-free survival (P=0.0147 and 0.0417, respectively). No prognostic information was supported by pS2 protein or EGF-R measurements. In multivariate analysis, histological grade, cath D and c-erbB-2 oncoprotein remained independent predictors of recurrence (P=0.005, 0.0361 and 0.0321, respectively). By combining low levels of cath D and c-erbB-2 oncoprotein in histological grade I or II tumors, we identified a subgroup of patients with a 100% relapse-free survival probability at 6 years of follow-up. Moreover, the subgroup of patients with histological grade I or II tumors and high values of both cath D and c-erbB-2 oncoprotein showed a prognosis as poor as the subgroup defined by histological grade III alone, respectively 66% and 70% relapse-free survival at 6 years of follow-up. In conclusion, the combination of conventional prognostic factor (histological grade) and biochemical factors (cath D and c-erbB-2 oncoprotein) enabled us to identify, in this preliminary study, a subgroup of patients having an increased risk of relapse in a group (node-negative patients with low histological grade tumors) considered as good prognosis.

Advances in diagnostic practices affect thyroid cancer incidence in France.

OBJECTIVE: To analyse trends in diagnostic practices of thyroid diseases and to relate them to the increase in thyroid cancer incidence in France over time. DESIGN: From 1980 to 2000, a French retrospective multicentric (three endocrinology and three nuclear medicine centres) study of thyroid diseases was conducted on 20 consecutive unselected patients' records, sampled every 5 years in each centre. METHODS: Characteristics of the population and diagnosis procedures (thyroid ultrasonography (US), radionuclide scan, cytology and hormonal measurements) were described over time. Changing trends in operated patients and in cancer prevalence were analysed as well as the impact of practices on cancer incidence. RESULTS: The study included 471 patients (82% female, mean age 46.7, range 9-84 years), referred for nodular thyroid diseases (66.7%) or thyroid dysfunctions (33.3%). A significant increase in US (3 to 84.8%) and cytological practices (4.5 to 23%), and a decrease (89.4 to 49.6%) in radionuclide scan procedures were observed over time. Although the proportion of patients undergoing surgery remained constant (24.8%), the prevalence of cancer increased among operated patients from 12.5 to 37% (P=0.006). In a Cox's proportional hazard model stratified on the clinical characteristics of patients, only the cytological practice, regardless of its results, was significantly associated with the occurrence of cancer: relative risk (RR)=4.4 (95% confidence interval (CI): 1.1-16; P=0.04). CONCLUSIONS: From 1980 to 2000, a major evolution in clinical practices has led to the increase in thyroid cancer reported in France. Such changes in medical, as well as in surgical and pathological, practices must be taken into account in incidence measurement.

Accuracy of the main Doppler methods for evaluating the degree of carotid stenoses (continuous wave, pulsed wave, and color Doppler).

OBJECTIVE: To compare the accuracy of the main Doppler methods for quantifying the degree of carotid stenoses in 133 patients. METHOD: seven parameters were measured: maximum velocity (V.max) inside the stenosis (by pulsed wave [PW]), grade and index of spectral disturbance (STI) at the outlet of the stenosis (by PW and continuous wave [CW]), ratio of velocities I(IC/CC) in the internal and common carotid (by PW), and ratio of vessel cross-section and residual lumen area (%Color) inside the stenosis (color Doppler). The reference methods were the grades of spectral disturbance and the STI (by CW), already validated against endarterectomy specimens. CONCLUSION: For poststenosis measurements, a high correlation was found between the grades or STI measured by PW and CW (reference method). The measurement of these parameters was easier in PW mode. For intrastenotic velocity, the increase in V.max was not proportional to the degree of stenosis, and V.max showed large fluctuations for the same degree of stenosis. I(IC/CC) also showed large fluctuations for the same degree of stenosis. The correlation was poor for these two parameters, which could only be used for detecting two groups of stenosis: >75% or >90% in area. Color Doppler (conventional and power) routinely overestimated the degree of stenosis by 10%-15% but correlated better with the reference method and was more accurate and reproducible than V.max. A special procedure can be used to avoid this overestimation and improve the accuracy of the color Doppler.

Rapid quality control for testing the radiochemical purity of 99Tc(m)-tetrofosmin.

We describe a new thin-layer chromatography (TLC) method to evaluate the radiochemical purity of 99Tc(m)-tetrofosmin without the drawbacks of toxicity, solvent ratios and time requirement associated with the standard TLC method. The new method uses miniaturized instant TLC plates impregnated with silica gel (ITLCTM/SG, 2.5 x 10 cm) for the stationary phase and 2-butanone for the mobile phase. The standard TLC method was performed with ITLCTM/SG plates (5 x 20 cm) and dichloromethane/acetone (65:35, v/v). Thirty five preparations were analysed by both methods with a storage phosphor imaging system to determine the percentages of hydrolyzed-reduced 99Tc(m) compound (99Tc(m)O2), 99Tc(m)-tetrofosmin and free 99Tc(m)-pertechnetate (99Tc(m)O4(-)). Using the miniaturized TLC method, 99Tc(m)-tetrofosmin had a mean Rf value of 0.55 (standard deviation, 0.05), while 99Tc(m)O4(-) migrated with the solvent front (Rf=1) and 99Tc(m)O2 remained at the origin of the strips (Rf=0). No significant difference was found between miniaturized and standard TLC methods for the radiochemical purity of 99Tc(m)-tetrofosmin using the Wilcoxon matched-pair signed-rank test (P=0.82). Furthermore, the two methods showed a good correlation as measured by the Spearman rank coefficient (r=0.89) and were in perfect agreement, with a kappa index of +1, for a cut-point between positive and negative set at 90%. In conclusion, the results indicate that the miniaturized TLC method is effective for the routine evaluation of the radiochemical purity of 99Tc(m)-tetrofosmin, without some of the drawbacks of the standard method.

Abdominal compartment syndrome in patients with burns.

Abdominal compartment syndrome (ACS) is a well-recognized perioperative complication that occurs in patients who undergo intra-abdominal operations and who require extensive fluid resuscitation. The classic presentation of this syndrome includes high peak airway pressures; oliguria, despite adequate filling pressures; and intra-abdominal pressures of more than 25 mm Hg. A decompressive laparotomy performed at the bedside can alleviate ACS. If left untreated, sustained intra-abdominal hypertension is often fatal. In the literature, ACS has been described in pediatric patients with burns but not in adult patients with burns. This article describes 3 adults who sustained burns of more than 70% of their body surface areas, who required more than 20 L of crystalloid resuscitation, and who developed ACS during their resuscitation after the burn injury. The mortality rate among these patients was 100%, which confirms the grave consequences of this syndrome. In our institution, intra-abdominal pressure is now routinely measured as part of the burn resuscitation process in an attempt to diagnose and treat this syndrome earlier and more efficaciously. It is recommended that the possibility of ACS be considered when diagnosing any patient with burns who develops high airway pressures, oliguria, or both.

[A comparative study of the Doppler methods for evaluation of the degree of carotid artery stenosis. Continuous, pulsed, color Doppler]. / Etude comparative des méthodes Doppler pour l'évaluation du degré des sténoses carotidiennes. Doppler continu, pulsé, couleur.

OBJECTIVE: Compare various Doppler methods for the quantification of the degree of stenosis on 85 patients. METHOD: the following parameters were measured: maximal velocity (Vmax) inside the stenosis (PW), grades of spectral disturbances at the outlet of the stenosis (PW-CW), index of spectral disturbance (STI) at the outlet of the stenosis (PW-CW), ratio of velocities I(IC/CC) in internal and common carotid (PW), ratio of vessel cross section and residual lumen area (% STEN) by color Doppler. The reference method was the Grades of spectral disturbance and the index of stenosis measured post stenosis. (Method validated against angiography and pieces of endarterectomy.) The following comparisons were done; grades and STI by CW against grades and STI by PW, Vmax (PW) against grade and STI, % STEN (color) against grade and STI, % STEN (color) against Vmax (PW), I(IC/CC) (PW) against grade and STI, I(IC/CC) (PW) against Vmax. CONCLUSION: (a) grades or stenosis index : showed the best reproductibility; (b) a high correlation was found between the grades or stenosis index post stenosis measured by CW or PW; (c) Vmax was not proportional to the stenosis degree and showed large fluctuations for the same stenosis degree; (d) the I(IC/CC) showed large fluctuations for the same stenosis degree, the correlation was poor for this velocity ratio. Both Vmax and I(IC/CC) allow to detect only 2 groups of stenosis > 75% or > 90% in area; (e) color doppler over-estimate stenosis degree by approximately 20% but was more accurate and reproducible than Vmax. An appropriate procedure was designed to avoid this over estimation.

[Quantification of carotid atheroma, by vascular ultrasonics and spectral analysis, after myocardial infarction. Apropos of 80 cases]. / Quantification de l'athérome carotidien, par l'échotomographie vasculaire et l'analyse spectrale, après infarctus du myocarde. A propos de 80 observations.

A prospective study of carotid artery atheroma by vascular echotomography and spectral analysis was performed in 40 patients with myocardial infarction and 40 control subjects. Carotid artery atheroma was commoner in the group of patients with myocardial infarction (72.5% +/- 6.8%), earlier (9 years), more commonly bilateral (37.5% +/- 7.6%) and more stenotic (32.5% +/- 7.4%) than in the control group (p less than 0.000a, p less than 0.0001 and p less than 0.002, respectively). The severity of carotid artery atheroma correlated with the site of coronary artery disease; the following significant relationships were found: stenosing 40% and/or bilateral carotid atherosclerosis and left anterior descending disease (p less than 0.02); carotid atherosclerosis and double or triple vessel disease (p less than 0.05). The authors conclude that detection of carotid artery atheroma after myocardial infarction is valuable for two reasons: it gives an indication as to the severity of the coronary disease; carotid endarterectomy may be considered at the same time as coronary artery bypass surgery.

[Value of the prosthetic patch after carotid endarterectomy]. / Intérêt du patch prothétique après endartériectomie carotidienne.

INTRODUCTION: Carotid patching after carotid endarterectomy remains a subject of controversy. However the recent medical literature shows that carotid patching lowers the incidence of both residual stenosis and early restenosis. Carotid patching seems also to lower the incidence of postoperative carotid occlusion. Some authors advocate systematic patching, others recommend a more selective use of carotid patching, among patients with small caliber carotid artery and among those with restenosis. STUDY: We have realized this study to determine (1) the incidence of restenosis after direct closure in patients with internal carotid artery of more than 3.5 mm internal diameter, (2) the adequate size of the patch in carotid arteries of less than 3.5 mm interval diameter (3), the adequate material to use for carotid patching. To answer these questions, we have done a prospective study of 188 carotid endarterectomy comparing direct closure (Group A), saphenous patch (Group B), and prosthetic Gore-Tex patch (Group C) with randomization between saphenous and prosthetic patch. RESULTS: In this study we were unable to show any difference among the three groups concerning postoperative mortality and neurologic complications. However we have been able to show more residual stenosis in group A than in groups B and C. One saphenous patch rupture occurred in Group B. After one year follow-up, five out of 43 restenosis occurred in Group A (11.6%). The rate of restenosis in groups B and C was 1.5% (2/135). In group B, six patients (8.7%) had a dilatation of the saphenous patch of more than 50% of their initial diameter. CONCLUSIONS: In this study, carotid patch seems to lower the incidence of residual stenosis and early restenosis in small diameter internal carotid arteries. Carotid patching with a 5 mm diameter PTFE patch seems to be the ideal choice after carotid endarterectomy. Furthermore, prosthetic patching carry no risk of dilatation or rupture and spare the saphenous vein.

[Basedow's disease and thyroid nodules. A common association]. / Maladie de Basedow et nodules thyroïdiens. Une association non exceptionnelle.

The frequency of thyroid cancer associated with Graves' disease is a controversial subject. The authors retrospectively studied 110 consecutive patients operated for Graves' disease between 1991 and 1996. Each patient was evaluated by clinical and laboratory examination, ultrasound and isotope scan. None of the patients had a history of external beam cervical radiotherapy or radioactive iodine. All patients were treated by total or subtotal thyroidectomy. Thyroid nodules were detected in 28 patients (24 women, 4 men), and 6 of them corresponded to papillary carcinoma (5.5% of patients with Graves' disease and 21.4% of patients with Graves' disease associated with nodules). These data suggest the value of surgery in Graves' disease associated with thyroid nodules.

[Detection and quantification of carotid atheroma. Respective value of vascular ultrasonography, spectrum analysis and digital intravenous angiography]. / Dépistage et quantification de l'athérome carotidien. Intérêts respectifs de l'échotomographie vasculaire, de l'analyse spectrale et de l'angiographie numérisée intraveineuse.

This retrospective study involved 37 subjects who were examined by means of intravenous digitalised angiography, vascular ultrasonography and spectral analysis of the Doppler signal. The last two examinations were found to give the most precise images and functional information. The concordances between angiography and ultrasonography on the one hand and spectral analysis on the other were 82 and 90 per cent. The authors have established a protocol in order to limit and systematize these examinations during screening for carotid atheroma: the risk factors are weighted; a score is obtained by summation; depending on the value of this score and the patient's age, the investigation procedure is pursued or not. The sequence always consists of ultrasonography followed by spectral analysis when plaque is detected and by angiography when the plaque is stenotic or ulcerated. In symptomatic patients, ultrasonography and digitalised angiography are performed routinely.

[Postoperative hypoglycemia after excision of pheochromocytoma. A case]. / Hypoglycémie postopératoire après ablation d'un phéochromocytome. Une observation.

A case of hypoglycaemia consecutive to excision of a bilateral phaeochromocytoma in a 33-year old patient with Sipple's syndrome is reported. The severity of the hypoglycaemia (1.3 mmol/l) accounted for the brain lesions which ultimately resulted in the patient's death. Eight cases of hypoglycaemia occurring in similar circumstances have been published. The condition is due to the massive release of insulin during the hours that follow removal of the tumour. This results in the persistence of the peri-operative hyperglycaemic stimulation and in the suppression of the previous inhibition of insulin secretion due to alpha-adrenergic stimulation of catecholamines in the beta-cells of Langerhans' islets.

Xerostomia and medication: a cross-sectional study in long-term geriatric wards.

OBJECTIVE: The purpose of this study was to determine the prevalence of xerostomia in old people living in long-term geriatric wards, and to measure the relationship between xerostomia and etiologic factors such as age and medication (total number of medications, xerogenic medications, anticholinergic medications and medications that induce hypersialorrhea). DESIGN: An observational retrospective, comparative, multicentre epidemiological study. SETTING: Long-term geriatric wards, in Reims, France. PARTICIPANTS: 769 old people living in long-term geriatric wards. MEASUREMENTS: Prevalence of xerostomia assessed from age, total number of medications, xerogenic medications, anticholinergic medications and those that induce hypersialorrhea. Multivariable logistic regression was used to calculate Odds Ratios (OR) and their 95% Confidence Intervals (95% CI). RESULTS: Among 769 old people (average age 84.6±8.4 years old), 287 residents suffered from xerostomia (37.3%). Significant predictors of xerostomia were: resident's age OR=1.56, 95% CI (1.30-1.88), p<0.0001 and anticholinergic medications OR=1.35, 95% CI (1.05-1.73), p=0.02. The only protective factor against xerostomia identified was medications that induce hypersialorrhea OR=0.81, 95% CI (0.67-0.98), p=0.03. The total number of medications and xerogenic medications did not play a significant role in xerostomia. CONCLUSION: Increasing Age and anticholinergic medications induce a dry mouth. Conversely, the total number of medications and xerogenic medications do not influence xerostomia. Medications that induce hypersialorrhea protect against the occurrence of dry mouth.

Global context effects on musical expectancy.

The effects of global harmonic contexts on expectancy formation were studied in a set of three experiments. Eight-chord sequences were presented to subjects. Expectations for the last chord were varied by manipulating the harmonic context created by the first six: in one context, the last chord was part of an authentic cadence (V-I), whereas in the other, it was a fourth harmonic degree following a full cadence (I-IV). Given this change in harmonic function, the last chord was assumed to be more expected in the former context, all the other local parameters being held constant. The effect of global context on expectancy formation was supported by the fact that subjects reported a lower degree of completion for sequences ending on an unexpected chord (Experiment 1), took longer to decide whether the last chord belonged to the sequence when the last chord was unexpected (Experiment 2), and took longer to decide whether the last chord was consonant or dissonant when it was unexpected (Experiment 3). These results are discussed with reference to current models of tonal cognition.

[Variations in blood magnesium in women according to age. Preliminary note]. / Variations de la magnesemie chez la femme en fonction de l'age. Note preliminaire.

PIP: Plasma and erythrocyte (RBC) magnesium levels were determined by atomic absorption spectrometry in 344 women aged 13-70 and in 209 men. The overall mean magnesium (Mg) contents were 52.8 mg/l in RBC's and 19.64 in plasma in women averaging 37.08 years, and 54.11 in RBC's and 20.38 in plasma in the men. When the women were grouped by age, those 13-20 years had the highest RBC and plasma Mg of all the cycling women. Those 23-24 years old had the lowest RBC Mg. The 65 menopausal women had significantly higher RBC Mg levels. Women over 45 had significantly higher plasma Mg than those 23-49 years. There were no variations with age in men, nor were there any relationships in women with cholesterolemia, weight, or height. Estrogens, 17-ketosteroids, or oral contraceptives may have caused low Mg levels in women.^ieng

Role of H-2 and non-H-2 genes in the control of blood magnesium levels.

Red blood cell (RBC) and plasma (P) magnesium levels have been determined in 372 male mice of 13 inbred and H-2 congenic strains with C3H or B10 genetic backgrounds. Several groups of individuals belonging to the same strains have been tested at various times over a 2-year period to verify the results. Time and interstrain variations are highly significant for both RBC and P Mg. Statistical analyses made either with or without corrections for the time effect show that the largest variations are due to the genetic background (P less than 10(-10) ), the effect of the H-2 complex being smaller but nevertheless highly significant (P less than 10(-4) to 10(-6) ), except for the RBC Mg of the strains with B10 background. These findings can be compared with those previously obtained in man, and they demonstrate the high heritability of blood Mg concentration and its association with the major histocompatibility complex or with closely linked genes.

Intra-abdominal hypertension and abdominal compartment syndrome in burn patients.

BACKGROUND: Intra-abdominal hypertension (IAH) and abdominal compartment syndrome (ACS) are known to occur in patients after major abdominal surgery. The incidence of IAH and ACS in the burn population is not known. METHODS: We prospectively recorded the intra-abdominal pressures of major burn patients admitted to our burn center from February 1999 to September 1999. A bladder pressure greater than 25 mm Hg was diagnosed as IAH. ACS was diagnosed when pulmonary compliance decreased in association with persistent IAH and was treated with abdominal decompression. RESULTS: Ten patients were placed on the protocol; of these, seven developed IAH. Five responded to conservative treatment. Two patients with 80% body surface area burns developed ACS and required decompression. CONCLUSIONS: IAH occurs commonly in major burn patients, and ACS is seen regularly in patients with more than 70% body surface area burns. We recommend bladder pressure measurements after infusion of more than 0.25 L/kg during the acute resuscitation phase and for peak inspiratory pressures greater than 40 cm H2O. Whereas ACS warrants surgical decompression of the abdominal cavity, IAH usually responds to conservative therapy.