Mechanisms underlying effects of nocturnal ventilation on daytime blood gases in neuromuscular diseases.

The hypothesis that, in neuromuscular and chest wall diseases, improvement in central respiratory drive explains the effects of night-time ventilation on diurnal gas exchanges was tested. The effects at 6 months, 1, 2 and 3 yrs of intermittent positive pressure ventilation (IPPV) on arterial blood gas tension, pulmonary function, muscle strength, sleep parameters, respiratory parameters during sleep and ventilatory response to CO2 were evaluated in 16 consecutive patients with neuromuscular or chest wall disorders. As compared with baseline, after IPPV daytime arterial oxygen tension (Pa,O2) increased (+2.3 kPa at peak effect) and arterial carbon dioxide tension (Pa,CO2) and total bicarbonate decreased (-1.8 kPa and -5 mmol x L(-1), respectively) significantly; vital capacity, total lung capacity, maximal inspiratory and expiratory pressures and alveolar-arterial oxygen gradient did not change; the apnoea-hypo-opnoea index and the time spent with an arterial oxygen saturation (Sa,O2) value <90% decreased (-24 and -101 min, respectively), sleep efficiency and mean Sa,O2 increased (+16% and +5%, respectively); and ventilatory response to CO2 increased (+4.56 L x min(-1) x kPa(-1)) significantly. The reduction in Pa,CO2 observed after IPPV correlated solely with the increase in the slope of ventilatory response to the CO2 curve (r=-0.68, p=0.008). In neuromuscular or chest wall diseases, improvement of daytime hypoventilation with nocturnal intermittent positive pressure ventilation may represent an adaptation of the central chemoreceptors to the reduction of profound hypercapnia during sleep or reflect change in the quality of sleep.

Once-daily sparfloxacin versus high-dosage amoxicillin in the treatment of community-acquired, suspected pneumococcal pneumonia in adults. Sparfloxacin European Study Group.

The objective of this randomized, double-blind, multicenter study of 329 adult patients requiring hospitalization was to compare the safety and efficacy of sparfloxacin at a dosage of 200 mg once daily (following a 400-mg loading dose on day 1) with those of amoxicillin given as a 1-g oral dose three times daily for treatment of community-acquired pneumonia suspected to be due to Streptococcus pneumoniae. Success of treatment was determined by a combination of clinical assessment and chest radiography. Pneumococcal pneumonia was the confirmed diagnosis for 177 patients (54%). Overall rates of success among evaluable patients were equivalent between drugs, both at the end of treatment (sparfloxacin, 92%; amoxicillin, 87%) and at follow-up (sparfloxacin, 89%; amoxicillin, 84%). Sparfloxacin was well-tolerated and produced fewer gastrointestinal effects than amoxicillin. In conclusion, sparfloxacin is a safe and effective alternative to high-dose amoxicillin for the treatment of suspected pneumococcal community-acquired pneumonia.

Study design, methodology and statistical analyses in the clinical development of sparfloxacin.

Many publications in the past 10 years have emphasised the difficulties of evaluating anti-infective drugs and the need for well-designed clinical trials in this therapeutic field. The clinical development of sparfloxacin in Europe, involving more than 4000 patients in ten countries, provided the opportunity to implement a methodology for evaluation and statistical analyses which would take into account actual requirements and past insufficiencies. This methodology focused on a rigorous and accurate patient classification for evaluability, subgroups of particular interest, efficacy assessment based on automation (algorithm) and individual case review by expert panel committees. In addition, the statistical analyses did not use significance testing but rather confidence intervals to determine whether sparfloxacin was therapeutically equivalent to the reference comparator antibacterial agents.

Severe community-acquired pneumococcal pneumonia. The French Study Group of Community-Acquired Pneumonia in ICU.

Streptococcus pneumoniae is the most frequent pathogen of severe community-acquired pneumonia (CAP) necessitating hospitalization. The main objective of this multicentre prospective study was to determine the value of clinical, biological, and radiological features for predicting pneumococcal etiology and to define prognostic factors. Streptococcus pneumoniae was isolated in 43/132 patients (33%) with CAP requiring ICU treatment. The mean age of the patients with pneumococcal pneumonia was 55 +/- 17 (SD) yrs and 34 were male. On admission, 14 patients with pneumococcal pneumonia were in shock, 24 were mentally confused, and 27 required mechanical ventilation during their hospitalization. Among the clinical, biological, and radiological features, fever > 39 degrees C, pleuritic chest pain, lobar distribution or alveolar consolidation, and an increase in immature granulocytes > or = 5% of WBC were more frequent in pneumococcal pneumonia than in other etiologies. Mortality was 35%. Fatal outcome was significantly related to the presence of impaired alertness, septic shock, mechanical ventilation, acute renal failure, and bacteremic pneumonia.

Severe community-acquired pneumonia. Etiology, epidemiology, and prognosis factors. French Study Group for Community-Acquired Pneumonia in the Intensive Care Unit.

A prospective study of 132 patients with severe community-acquired pneumonia (CAP) treated in the ICU was carried out to determine the causative agents, the value of the clinical, biological, and radiologic features in predicting the etiology, and to define prognostic factors. The study group included 98 men and 34 women (mean age: 58 +/- 18 years). The most frequent underlying condition was COPD (51 patients, 39 percent). On admission, 35 patients were in shock, 71 were mentally confused, and 81 (61 percent) required mechanical ventilation during their hospitalization. The clinical, laboratory, and radiologic parameters were of little value for predicting the etiology in patients with severe CAP. An etiologic diagnosis was made in 95 (72 percent) patients. The most frequent pathogens were Streptococcus pneumoniae (43 cases [45 percent]), Gram-negative bacilli (14 cases [15 percent]), and Haemophilus influenzae (14 cases [15 percent]) Mortality was 24 percent. It was significantly associated with a age more than 60 years, septic shock, impairment of alertness, mechanical ventilation requirement, bacteremic pneumonia, and S pneumoniae or Enterobacteriaceae as the causes of the pneumonia. Recommendations for antibiotic chemotherapy in patients with severe CAP admitted to the ICU are included.

[Treatment of community-acquired pneumonia by pristinamycin (Pyostacine 500). Results of a non comparative open study]. / Traitement des pneumopathies communautaires par la pristinamycine (Pyostacine 500). Résultat d'une étude ouverte non comparative.

UNLABELLED: Activity of natural streptogramin (NSG) appears well adapted to pathogens responsible for CAP. The goal of this multicenter pilot study was to bring first data about efficacy of NSG in treatment of CAP. PATIENTS METHOD: Ten days of a NSG (1 gr b.i.d. or t.i.d.) regimen was administered to 46 hospitalized adult patients for CAP defined with fever > 38 degrees C, respiratory symptoms and X-ray opacity. Severely ill patients were excluded. A broncho-pulmonar sample (expectoration or trantracheal aspiration or protected distal sample) was performed in all patients. RESULTS: two patients were excluded because of pulmonary embolism (n = 1) or tuberculosis (n = 1) and 44 patients were analyzed. 50% of them had associated disease, 20% had failure of prior antibiotherapy. At inclusion, mean fever was 39.2 +/- 0.7 degrees C, respiratory rate was 22 +/- 5/mn, PaO2 was 74 +/- 10 mmHg, chest X-ray showed bilateral opacity in 16%, unilateral in 84% and pleural fluid level in 6 cases. Etiological diagnosis was determined in 70% of cases. Streptococcus pneumoniae (n = 14), Haemophilus influenzae (n = 5), Legionella pneumophila (n = 2), Mycoplasma pneumoniae (n = 2) and Chlamydia psittaci (n = 1) were the most frequent isolated pathogens. 40 patients (91%) were cured with NSG and delay to obtain apyrexia was 4.4 +/- 3.9 days. NSG was stopped in 4 patients: 1 clinical and bacteriological failure (Klebsiella pneumoniae), 2 clinical failures (1 pneumococcus with purulent pleurisy, 1 pneumococcus with worsening of respiratory status), 1 patient with resistant H. influenzae strain in spite of favourable clinical evolution. NSG was well tolerated in 86% of patients. CONCLUSION: these data invite to carry on evaluation of first line therapy of CAP with NSG.

[Community-acquired pneumonia in healthy adults: 188 patients treated with spiramycin in private practice]. / Pneumopathies communautaires de l'adulte sain: 188 patients traités en médecine libérale par la spiramycine.

One hundred and eighty eight outpatients with community acquired pneumonia have been treated by spiramycin in general practice. Community acquired pneumonia was defined by the association of fever > or = 38 degrees C, respiratory symptoms as cough, sputum production, dyspnea or thoracic pain, and pulmonary opacity on the chest X-Ray. The mean age of patients was 44.7 +/- 16.6 and few of them had concomitant chronic illness, as cardiovascular (9%) or bronchopulmonary disease (9%). Twenty one percent of patients have been included after a previous antibiotherapy failure. In 92% on these cases, prior antibiotherapy was a beta lactam. At inclusion, the fever was greater than 39 degrees C in 56% of patients, 58% had localized crepitations at the chest auscultation. The chest X-Ray was performed 1.4 +/- 2.1 days after inclusion and showed a lobar consolidation in 77%. One third of patients presented a clinical picture evoking acute bacterial pneumonia. One hundred and seventy one patients have been reviewed for a second evaluation 4 +/- 1.5 days after inclusion. One hundred and eighty seven patients have visited for the long term follow up 19 +/- 6.5 days after the onset of treatment. Ninety six per cent of them have consulted with a control chest X-ray. At this visit, the antibiotherapy was changed in 2 other patients with of failure. Overall, 83% of patients were clinically and radiologically cured by Spiramycin 3 MU twice a day for 13 +/- 3.5 days. Fourteen percent of patients were improved without necessity of changing the antibiotic regimen. This study confirms the efficacy of spiramycin in the management of community acquired pneumoniae in general practice, either in first line therapy of after the failure of beta lactam.

[Randomized therapeutic trials of community-acquired lung diseases. Analysis of studies published between 1978 and 1988]. / Essais thérapeutiques randomisés des pneumopathies communautaires. Analyse des études publiées entre 1978 et 1988.

The authors have evaluated the methodology of 21 randomized therapeutic trials concerning community acquired pneumonia. Only 33% of these trials were entirely devoted to community acquired pneumonia; the remainders included various respiratory infections. Only 8 trials were of the double-blind type. The presence of radiological opacity was mentioned as a criterion of inclusion in only 10 trials, and in 9 trials the diagnosis of pneumonia was not defined. The criterion of judgement, which separates success from failure, remained undefined in 6 trials. The number of patients analyzed was much lower than that of patients admitted because of exclusions for negative cultures or for isolation of a bacteria resistant to one of the antibiotics tested. Finally, in only 2 of the 21 trials it was concluded that an antibiotic was superior to the other(s). Clearly then, the quality of these randomized therapeutic trials needs to be improved by a better definition of their purpose and of the criteria of patients' admission, and by analysis of an intention to treat which is the nearest thing to the future use of the drug under study.

Trial of normobaric and hyperbaric oxygen for acute carbon monoxide intoxication.

The value of hyperbaric oxygen in the treatment of acute carbon monoxide intoxication was assessed in 629 adults who had been poisoned at home in the 12 h before admission to hospital. In patients without initial impairment of consciousness (group A) the effect of 6 h of normobaric oxygen (NBO) (group A0, n = 170) was compared with that of 2 h of hyperbaric oxygen (HBO) at 2 atmospheres absolute (ATA) plus 4 h NBO (group A1, n = 173). At the 1 month follow-up 66% of A0 and 68% of A1 patients had recovered. In patients with initial impairment of consciousness the effect of one session of HBO (group B1, n = 145) was compared with that of two sessions (group B2, n = 141); all group B patients also received 4 h of NBO. At 1 month of follow-up 54% group B1 and 52% group B2 patients had recovered. The 7 patients left with neuropsychiatric sequelae (3 B1, 4 B2) and the 4 who died (2 B1, 2 B2) had all presented with coma. HBO was not useful in patients who did not lose consciousness during carbon monoxide intoxication, irrespective of their carboxyhaemoglobin level, nor were two sessions of HBO in patients who sustained only a brief loss of consciousness. The prognosis is poorest for those presenting with coma; the trial needs to be pursued in this group of patients until the power of the study is sufficient to demonstrate the value or otherwise of HBO.

[Extrapyramidal syndrome after cardiocirculatory incompetence]. / Syndrome extra-pyramidal après incompétence cardio-circulatoire.

A 43 year-old woman suffered a cardio-circulatory arrest with a post-anoxic coma during 24 hours. This was followed by and akinetic-hypertonic syndrome. There was also dystonia of both hands and of right big toe. After and initial mutism, the patient spoke with dysarthria, a monotonous weak voice of poor timbre and low vocal volume. She had in addition mood disturbances with indifference to her condition and compulsive activity. Extrapyramidal syndromes after ischemic anoxia are rare, when compared to their relative frequency after carbon monoxide poisoning. Early CT scan with contrast can identify symmetrical and bilateral lenticulocaudal high densities and MRI is also useful for the diagnosis.

[Anoxic encephalopathy after cardiocirculatory insufficiency. Neuropathological study apropos of 16 cases]. / Encéphalopathie anoxique après incompétence cardio-circulatoire. Etude neuropathologique à propos de 16 cas.

Sixteen cases of anoxic encephalopathy in adult patients admitted to the intensive Care Department of Raymond Poincaré Hospital (Garches) have been selected on the following criteria: resuscitation by external cardiac massage for cardio-respiratory failure, without any previous history of anoxia and with detailed data on the subsequent evolution of neurological signs and symptoms. Main clinical features were compared to the results of the neuropathological examination. The pattern and the distribution of changes are detailed. The cerebral cortex was always involved by diffuse ischemic cell changes or by laminar necrosis. The Sommer's sector of Ammon's horn was affected in 15 cases, the basal ganglia in 14, the cerebellum in 11, the brain stem in 6. The very rarely mentionned necrotic brain stem changes, which involved inferior colliculi, periaqueductal gray matter and substantia nigra were sometimes associated with lesions of the floor of the IVth Ventricle and of the mamillary bodies. They were different from Wernicke's encephalopathy with could be dismissed on clinical and pathological grounds. No clinical signs or symptoms specific for this distribution of changes could be found by the retrospective study of the clinical files.