[Cervical pain radiating to the upper limb]. / Cervicalgies irradiant dans le membre supérieur gauche.

A 31 years old male, HIV negative, with past history of sarcoidosis with articular and pulmonary involvement, without immuno-suppressive therapy, presents two years later with cervical pain radiating to the upper limb. Cervical imaging shows several para vertebral collections and lytic bone lesions. A diagnosis of tuberculous osteo-arthritis is established based on imaging and mycobacterial data.

Un homme de 31 ans, HIV négatif, ayant des antécédents de sarcoïdose avec atteinte articulaire et pulmonaire, sans traitement immuno-supresseur, présente deux ans plus tard des cervicalgies à gauche avec irradiation au niveau du membre supérieur. L'imagerie cervicale documente plusieurs collections para-vertébrales ainsi que des lésions lytiques osseuses. Un diagnostic d'ostéo-arthrite tuberculeuse est posé sur base de l'imagerie et des prélèvements mycobactériologiques.

[Management of chronic cough]. / La prise en charge de la toux chronique.

Chronic cough, defined as lasting more than 8 weeks, is a frequent and difficult problem. Since 1981, the north American group of Irwin and coworkers has proposed a diagnostic algorithm with chronic cough being explained in a vast majority of cases by three possible diagnoses: asthma, chronic rhino-sinusitis and gastrooesophageal reflux. This algorithm has been amended in order to include eosinophilic bronchitis and has further been severely criticized because of frequent failure in clinical practice. In 2008, Pavord and Chung have proposed to put the emphasis in chronic cough on non specific cough hyperreactivity, with the aetiological factors suggested by the Irwin group acting at most as modulating agents. Severe or persistent chronic cough should be quantitatively assessed, using for instance a visual analogue scale or a cough specific quality of life questionnaire. Where treatment for chronic cough is concerned, the sole definitely effective interventions are smoking cessation and discontinuation of a converting enzyme inhibitor. Long term inhaled steroids are also effective in case of eosinophilic cough (defined on basis of eosinophilia in induced sputum or increased level of exhaled NO). In case of chronic cough unresponsive to the hereinabove described management, an antitussive agent should be considered. As codeine is relatively ineffective, research about new antitussive agents should be encouraged.

[Three pregnancies on nasal CPAP: a case report]. / Trois grossesses sous CPAP nasale: à propos d'une observation.

We report on a sleepy woman, suffering from morbid obesity, with a diagnosis of severe sleep apnea syndrome made at the age of 30 year, treated with nocturnal ventilatory support (nasal CPAP). The patient had an history of preeclampsia during a first pregnancy. In the following years, this patient remained very compliant with nasal CPAP, was no longer sleepy and was three times pregnant, without any complication.

In vitro antiproliferative activity of combinations of ether lipid analogues and DNA-interactive agents against human tumor cells.

Ether lipid analogues of platelet-activating factor (1-octadecyl-2-acetyl-sn-glycero-3-phosphocholine) possess a wide range of biological activities, including inhibition of neoplastic cell growth in vitro and in vivo. This activity is believed to be membrane mediated. Three different ether lipid analogues, 1-octadecyl-2-methyl-rac-glycero-3-phosphocholine, 1-thiohexadecyl-2-ethyl-rac-glycero-3-phosphocholine, and 4-amino-methyl-1-[2,3-(di-n-decyloxy)-n-propyl]-4-phenylpiperidine , were combined with three DNA-interactive drugs, Adriamycin, 4-hydroperoxycyclophosphamide, and cisplatin, in the expectation that combinations of drugs with different mechanisms of action might show enhanced antitumor activity. The in vitro antiproliferative activity of the combinations was measured with a semisoft agarose clonogenic assay of an ovarian adenocarcinoma cell line. Various permutations of drug combinations were studied. Isobologram analyses and different treatment schedules were performed. Enhanced antiproliferative activity was found with combinations of ether lipids with DNA-interactive drugs in comparison with single agents. Statistical evaluation of the data indicated that the increase in activity was due to an additivity phenomenon. Neither synergism nor antagonism was found.

Prostaglandin endoperoxide synthetase and the activation of benzo(a)pyrene to reactive metabolites in vivo in guinea pigs.

The role of prostaglandin endoperoxide synthetase in the in vivo activation of benzo(a)pyrene to reactive metabolites capable of interacting irreversibly with cellular macromolecules was studied in guinea pig liver, lung, kidney, spleen, small intestine, colon, and brain. DNA and protein covalent binding experiments were made after systemic administration of acetylsalicylic acid (200 mg/kg) followed by radiolabeled benzo(a)pyrene (4 microgram/kg). Results are compared with a control situation in which the prostaglandin endoperoxide synthetase inhibitor (acetylsalicylic acid) was not administered. No decrease in the level of DNA or protein benzo(a)pyrene-derived covalent binding was observed in any of the tissues studied.

Prostaglandin and thromboxane synthesis by Lewis lung carcinoma during growth.

The five stable metabolites [prostaglandin F2 alpha, prostaglandin D2, prostaglandin E2 (PGE2), thromboxane B2, and 6-keto-prostaglandin F1 alpha] of arachidonic acid (AA) via the cyclooxygenase pathway were measured by high-resolution gas chromatography-mass spectrometry in Lewis lung carcinoma homogenates at various times after tumor implantation (11 to 25 days). Vegetating and necrotic sections of the primary tumor and lung metastases were examined. Vegetating tumor showed a very active AA metabolism. Synthesis of PGE2, the most abundant product, markedly increased during tumor growth (up to 30 micrograms/g). A high and increasing synthetic capacity was also noted for prostaglandin D2 (up to 9 micrograms/g). Minor time differences and lower levels (up to 1.4 micrograms/g) were found for the other AA metabolites. PGE2 and prostaglandin D2 were the major products in necrotic tumor, too, but synthesis was markedly less than in vegetating tumor, and no increase was noted over time. Metastatic tissue showed a different AA metabolic profile, as compared to primary tumor and surrounding lung tissue, with PGE2 and 6-keto-prostaglandin F1 alpha being the main metabolites.

Acute coronary syndrome and platypnoea-orthodeoxia with thoracic and interauricular septal aneurysms.

OBJECTIVE: Platypnea-orthodeoxia is a rare syndrome characterized by dyspnea induced by the upright position and relieved by supine position and an arterial deoxygenation increased by the upright position which improves during recumbency. Several anatomical factors that can alter the atrial anatomy and facilitate shunting through an interatrial defect have been related to this syndrome. In many cases, this syndrome has been associated with patent foramen ovale (PFO) and right-to-left shunt. Rarely platypnea-orthodeoxia syndrome has been described associated with an aortic and with an interauricular septal aneurysm too. CASE PRESENTATION: We present a case of platypnea-orthodeoxia syndrome in a 85-year-old woman with patent foramen ovale, interauricular septal aneurysm and ascending aortic aneurysms who was admitted for an acute coronary syndrome which could be of embolic origin and was responsible for ventricular fibrillation during the transfer to the hospital. PFO closure was performed by percutaneous device and right coronary artery obstruction was treated by transluminal angioplasty and stenting.

Effects of antineoplastic ether lipids on model and biological membranes.

Differential scanning calorimetry and electron spin resonance were utilized to measure the effects of di-ether glycerophospholipid analogs (EL) on the physical properties of model membranes and on the membrane fluidity of HL60 leukemic cells. 1-Octadecyl-2-methyl-rac-glycero-3-phosphocholine (ET-18-OMe) and 1-thiohexadecyl-2-ethyl-rac-glycero-3-phosphocholine (ET-16S-OEt) lower the transition temperature of dimyristoylphosphatidylcholine vesicles in a range of concentrations between 0.5 and 15 mol %. Studies conducted on the interaction of EL with a wide spectrum of different phospholipids, namely dipalmitoylphosphatidylcholine, 1-hexadecyl-2-palmitoylphosphatidylcholine, dipalmitoylphosphatidylethanolamine, and dielaidoylphosphatidylethanolamine confirmed the ability of EL to effect the physical properties of model membranes. Changes in calorimetric enthalpy were observed only with phosphatidylethanolamine-containing phospholipids. ET-18-OMe and ET-16S-OEt increased the membrane fluidity of HL60 leukemic cells labeled with the fatty acid spin label probe 5-nitroxystearate. These data demonstrate the ability of EL to partition into phospholipidic domains and to change their physical properties. Furthermore, they affect the membrane fluidity of whole cells. These effects indicate an interaction between EL and the plasma membrane which may be of importance in determining the cytotoxic activity against tumor cells exerted by EL.

Characterization of arachidonic acid metabolic profiles in animal tissues by high-resolution gas chromatography-mass spectrometry.

A standardized, highly specific routine method was developed for the quantitative profiling of cyclooxygenase metabolites of arachidonic acid in animal tissues. Whole homogenates were used to assess the potential capacity of tissues to metabolize endogenous arachidonic acid. Samples were analyzed by high-resolution gas chromatography-mass spectrometry in the selected ion monitoring mode. The screening of several rat tissues by this method revealed marked tissue-specificity in both the synthesis capacity and prostaglandin profile. The major products detected were: 6-ketoprostaglandin F1alpha for lung, stomach, muscle and heart; prostaglandin D2 for spleen, brain and liver; prostaglandin F2alpha for kidney and prostaglandin E2 for seminal vesicles. Marked species differences were found when guinea pig tissues were analyzed.

Synthesis and evaluation of neoplastic cell growth inhibition of 1-N-alkylamide analogues of glycero-3-phosphocholine.

Previously unreported analogues of the synthetic antitumor phospholipid ET-18-OMe (1-octadecyl-2-methoxy-rac-glycero-3-phosphocholine), in which the 1-ether oxygen has been replaced by an amido group, have been prepared and evaluated for in vitro cytotoxic effects and for inhibition of protein kinase C. The title compounds exhibit cytotoxic effects against several tumor cell lines and are approximately equipotent to ET-18-OMe. The compounds were also found to inhibit protein kinase C in an in vitro assay. This work is a continuation of our previous structure-activity studies on thio-substituted derivatives of ET-18-OMe.

Does an IV bolus of methylprednisolone relieve dyspnea in asthma exacerbations?

STUDY OBJECTIVES: To assess whether IV methylprednisolone exerts a specific early effect on dyspnea in patients with an exacerbation of asthma. DESIGN: Randomized, placebo-controlled, double-blind crossover trial. SETTING: Medium-sized university general hospital. PATIENTS: Twenty-five asthma patients attending the chest clinic with spontaneous complaints of increases in dyspnea and with a Borg scale dyspnea rating >/= 1 at rest. INTERVENTIONS: At 0 min, IV methylprednisolone (125 mg) vs saline solution; at 60 min, 5 x 500 microg terbutaline inhaled from an inhaler device. MEASUREMENTS AND RESULTS: Change in dyspnea was assessed with bipolar visual analog scale (VAS) (much more short of breath, -100%; much less short of breath, + 100%), FEV(1), and visual memory (using the Benton visual retention test). Eighteen subjects (mean age, 61 years) completed the study. At 5 min and 60 min, shortness of breath improved with no statistically significant difference between saline solution and methylprednisolone. The mean (SD) VAS rating at 60 min was 29% (39%) on the day that saline solution was administered and 36% (25%) on the day the steroid was administered. FEV(1) and Benton score did not significantly change from baseline on either study day. Shortness of breath and FEV(1) improved following terbutaline administration, with no significant difference between the days on which saline solution and the steroid were administered. In the seven subjects who were randomized to receive methylprednisolone on the first day, baseline dyspnea rated on the Borg scale was significantly lower on the second day (first day: median, 3; range, 3 to 4; second day: median, 2; range, 0.5 to 3; p = 0.040). CONCLUSIONS: We conclude that in patients with an exacerbation of asthma, an IV bolus of methylprednisolone does not reduce dyspnea more than saline solution after 5 min and 60 min.

Sleep apnea after 1 year domiciliary nasal-continuous positive airway pressure and attempted weight reduction. Potential for weaning from continuous positive airway pressure.

STUDY OBJECTIVE: To assess the effect of 1 year of therapy for sleep apnea syndrome (SAS) combining domiciliary nasal-continuous positive airway pressure (N-CPAP) and attempted weight loss on the severity of disease and to evaluate the potential for weaning from continuous positive airway pressure (CPAP). METHODS AND PROCEDURES: Ninety-five patients having a baseline apnea hypopnea index (AHI) greater than 10/h were prescribed N-CPAP at home. Weight loss was attempted by dietary counseling and by single ring vertical gastroplasty in those patients with a body mass index (BMI) greater than 40 kg/m2. Subjects were asked to return after 1 year for a full-night polysomnography (PSG) without CPAP and the results were compared with baseline PSG. RESULTS: Thirty-nine patients compliant to CPAP were evaluated. Weight had decreased from 108.3 +/- 29.0 to 99.7 +/- 17.7 kg as a result of dietary counseling (n = 36) or gastroplasty (n = 3). A significant improvement was found in AHI (66.5 +/- 28.7-->50.3 +/- 38.4/h; p < 0.05), maximal duration of apnea or hypopnea (66 +/- 22-->47 +/- 18 s; p < 0.001), minimal oxyhemoglobin saturation (62 +/- 16-->78 +/- 7%; p < 0.001), and stage shift index (SSI) (76 +/- 29-->62 +/- 28/h; p < 0.05). The drop in AHI correlated with the reduction in BMI (r = 0.47; p < 0.01) and with the decrease in SSI (r = 0.50; p < 0.001). Weaning from CPAP was proposed to six patients and succeeded in four (three with 29, 93, and 94 kg weight loss, respectively, and one subject with a normal unchanged weight). CONCLUSION: In 39 patients with SAS, 1-year domiciliary N-CPAP combined with weight loss resulted in a significant improvement in breathing during sleep and in sleep fragmentation, as judged from PSG without CPAP. Four subjects were successfully weaned, three of whom had in parallel a substantial decrease in weight.

Mild to moderate sleep respiratory events: one negative night may not be enough.

STUDY OBJECTIVES: Reports on the reproducibility of apnea-hypopnea indexes (AHIs) across sequential polysomnography (PSG) sessions are conflicting, leading to a lack of clear recommendations on the optimal use of this technique: is one night of monitoring sufficient or is a second night required in order to safely reject the diagnosis? DESIGN: Retrospective comparison of two consecutive nights. SETTING: Sleep unit of a tertiary-care facility. PATIENTS: Two hundred forty-three subjects with suspected sleep apneas. INTERVENTIONS: Two sequential PSG sessions in a sleep unit. MEASUREMENTS AND RESULTS: Using analysis of covariance for repeated measures, with age and body mass index as covariates and gender as a cofactor, a classic first-night effect was found for sleep variables. In addition, a night effect was demonstrated for sleep respiratory variables. Moreover, the high variability of AHIs showed that many patients had their condition diagnosed on only one of the two nights, and more often on the second night than on the first. The gain in detection by adding a second night when the results of testing on the first were negative was between 15% and 25%, according to the AHI obtained on night 1. CONCLUSIONS: Considering the disability associated with sleep apnea/hypopnea syndrome, as well as its global cost for society, the present study shows that it is worth performing two consecutive PSG sessions or at least a second one when the result of the first one is negative in all patients admitted for apnea detection.

Clinical profile of ioversol. A metaanalysis of 57 randomized, double-blind clinical trials.

RATIONALE AND OBJECTIVES: The authors characterize the clinical profile of ioversol, specifically in terms of radiographic efficacy and clinical tolerance. METHODS: Metaanalysis of data from all available randomized, double-blind trials, comparing ioversol with other nonionic contrast media in indicated procedures was conducted. A total of 3854 adult patients were studied (1931 ioversol, 1923 reference) from 57 clinical trials. RESULTS: Ioversol was considered diagnostic in 99.3% of examinations, with good to excellent enhancement quality in 89.3% of cases. In comparative evaluations, there was a 24% odds reduction of the investigator's nondiagnostic judgment and a 15% odds reduction of poor to fair quality in favor of ioversol. For tolerance, 20.2% and 3.3% of patients in the ioversol group reported moderate to severe sensation of heat and pain with a 10% odds reduction and a 3% odds increase, respectively. The incidence of drug-related adverse events was low: 76 (3.3%) patients in the ioversol group and 62 (2.9%) patients in control group. No statistically significant differences were noted. CONCLUSION: Based on these findings, the high-contrast efficacy and patient tolerance make ioversol a suitable agent, equivalent to other nonionic contrast media.

Trisomy 11 in preleukemia.

The clinical and cytogenetic findings of a patient with a preleukemic state and trisomy 11 are reported. Trisomy 11 was present as the sole karyotypic alteration at the time of overt leukemia. Trisomy 11 presents an additional chromosomal abnormality not previously described in preleukemia.

Cross-resistance pattern of cell lines selected for resistance towards different cytotoxic drugs to membrane-toxic phospholipids in vitro.

The synthetic ether lipids ET-18-OCH3 and BM41.440 and a derivative, hexadecylphosphocholine, were tested for inhibition of [3H]-thymidine uptake into a Chinese hamster ovarian cell line (AUXBl) and its multidrug-resistant subline selected for colchicine resistance (CHRC5). The activity of all three compounds against the multidrug-resistant subline was equal to or higher than that against the parent line. The same result was found for their activity against a human leukemic lymphoblastic cell line (CEM/O) and its methotrexate-resistant subline (CEM/MTX). In contrast, two multidrug-resistant cell lines selected for resistance to Adriamycin, the mouse leukemia cell line P388/ADR and the murine sarcoma cell line S180/ADR, expressed modest cross-resistance to the lipids as measured by thymidine uptake. Experiments performed using the trypan-blue dye-exclusion assay yielded comparable results, although this system revealed a slightly different sensitivity in showing the cytotoxicity of the drugs. By this assay, modest cross-resistance for ET-18-OCH3 and BM41.440 to Adriamycin was found only after 24 h incubation and decreased after 48 h incubation, with almost equal sensitivity to both drugs being shown by the parental (P388/W) and resistant lines (P388/ADR). Furthermore, findings from a human tumor-cloning assay were in accordance with these data, although they did not indicate cross-resistance for the P388/ADR cell line. These results suggest that certain ether lipids and derivatives might represent valuable anticancer drugs warranting further study in the setting of resistant disease.

Compliance with nasal continuous positive airway pressure assessed with a pressure monitor: pattern of use and influence of sleep habits.

The aim of the study was to assess compliance with nasal continuous positive airway pressure (N-CPAP) at home in patients with obstructive sleep apnoea syndrome (OSAS) and to search for predictors of compliance. We studied a cohort of 106 consecutive patients (91 men, 15 women) with a median apnoea hypopnoea index of 62.4 (range 21-132) h(-1), equipped at home with a Rem+ Soft device (Sefam, France), including a pressure monitor and a real-time clock. During the third and fourth months of treatment, the patients used their machine a median of 88% of days (16-100%), with a mean effective use of 5.6 (1.3-11.2) h per effective day. Residual apnoea index on N-CPAP, as recorded by the monitor, was 1.5 (0.3-27.6) h(-1). Mean clock-time for starting with N-CPAP was 23 h 54 min (21 h 34-01 h 42). The mean effective use per effective day correlated negatively with the minimal (and the mean) level of oxyhaemoglobin saturation (r(s) = -0.24, P < 0.05) while the percentage of days the machine was used correlated negatively with the percentage of slow wave sleep (r(s) = -0.22, P < 0.05) at baseline polysomnography. In a subset of 30 subjects, earlier start on N-CPAP correlated with longer use of the device in 22 patients (median r--0.48). We conclude that a pressure monitor allows reporting on compliance in terms of regularity (% of days the machine is used) and length of sleep on N-CPAP (effective use per effective day). These compliance variables show modest correlations with baseline polysomnographic features. Late bedtime should be discouraged as it might decrease compliance.

High leg motor activity in sleep apnea hypopnea patients: efficacy of clonazepam combined with nasal CPAP on polysomnographic variables.

The association of sleep apnea hypopnea syndrome (SAHS) with high leg activity in the same patient is a dilemma for the physician, as clonazepam, used to treat periodic leg movement syndrome (PLMS) can aggravate apneas, while nasal continuous positive airway pressure (nCPAP) can exacerbate PLMS. The present study aimed to compare nCPAP alone (n), nCPAP combined with clonazepam (n+c) and clonazepam alone (c) in patients with mild to moderate SAHS associated with high leg activity. Fourteen patients with an apnea hypopnea index (AHI) between 10 and 50 h(-1) and a leg movement index with regard to time in bed [LMI (TIB)] > 15 h(-1) on baseline polysomnography (b) were recorded on three consecutive nights with n, n+c and c, respectively. Leg movements were detected, using actigraphy, and were subsequently categorized into periodic, apnea- or hypopnea-related and nonperiodic movements (defined as neither periodic nor related to a respiratory event). The three treatments were successful in improving breathing [AHI b 26.1 (3.2) n 11.8 (2.4) n+c 5.0 (0.7) c 14.9 (1.8) h(-1)], leg activity [LMI (TIB) b 391 (4.8) n 22.5 (4.4) n+c 23.9 (3.9) c 22.6 (3.7) h(-1)] and sleep fragmentation [stage shift index b 373 (2.6) n 28.6 (1.6) n+c 25.6 (1.8) c 26.6 (1.6) h(-1)]. All types of movements were reduced, the effect being significant for respiratory events related and nonperiodic movements. Combination therapy was more effective than nCPAP alone in reducing the AHI and in improving sleep efficiency. We conclude that in patients with mild to moderate SASH associated with high leg activity, nCPAP improves nocturnal breathing and clonazepam reduces leg activity. More unexpectedly nCPAP is beneficial on leg activity and clonazepam on breathing, probably through a decrease in sleep fragmentation. The best results are obtained with combination therapy.

Perception of dyspnoea during acute changes in lung function in patients with either asthma or COPD.

The aim of the study was to evaluate the relationship between several lung function indices and perceived dyspnoea during bronchoconstriction. Acute changes in lung function were induced by inhaled histamine followed by terbutaline, in 12 asthmatics and 12 subjects with chronic obstructive pulmonary disease (COPD). A bipolar visual analogue scale (VAS), allowing subjects to report either improvement or worsening when moving off from a 'nochange' midpoint, was used to rate shortness of breath. Large swings in ratings were seen in all asthmatics and in seven out of 12 COPD subjects (high perceivers). Using linear regression of VAS rating against parallel change in lung function, on a within-subject basis, the highest degree of correlation between dyspnoea and objective response was found to involve the change in specific inspiratory resistance (sRin) in the asthmatics. In the five low perceivers, the ability to discriminate an increase in airway obstruction, estimated as the VAS/change in lung function slope, was very poor. Using a stepwise multiple regression analysis, the sensation of dyspnoea was found to be significantly related to the FEV1 and the sRin in the asthmatics, to the inspiratory vital capacity and the maximal inspiratory flow at 50% FVC (MIF50) in the COPD subjects with high perception, and to the MIF50 in the COPD subjects with low perception.

Diabetes insipidus from metastatic oat cell carcinoma: recovery after brain irradiation.

A hypothalamic metastasis was demonstrated by computed tomography in a 71-year-old patient, with previously unknown small cell lung cancer, who presented with diabetes insipidus and biological signs of hypothyroidism and hypogonadism. Brain irradiation resulted in resolution of polyuria, elevation of thyroid hormones, improvement of pituitary responsiveness to hypothalamic releasing hormones, and complete disappearance of contrast-enhanced suprasellar metastasis.