Pazopanib or placebo in completely resected stage I NSCLC patients: results of the phase II IFCT-0703 trial.

BACKGROUND: Adjuvant treatment in resected stage I non-small-cell lung cancer (NSCLC) is generally not recommended. Pazopanib is an oral tyrosine kinase inhibitor of VEGFR-1/2/3 and PDGFR-α/ß. We explored the feasibility and efficacy of adjuvant pazopanib in this population. PATIENTS AND METHODS: In this double-blind phase II/III trial, patients with resected stage I NSCLC were randomized to placebo or pazopanib 800 mg/day (P800) for 6 months with a two-step Fleming design. The primary endpoint was compliance (percentage of patients receiving ≥3 months pazopanib). From the interim analysis after 64 patients were included, the IDMC recommended reducing to pazopanib 400 mg/day (P400) due to insufficient compliance, with a one-step Fleming. Although unplanned, survival data were analyzed. RESULTS: A total of 71 patients were enrolled in each arm; 61% were male, 91% were smokers, median age was 60 years, 80% had pathological stage IA, and 16% had squamous cell carcinoma. Pazopanib compliance was 38% [95% confidence interval (CI) 23-55] with P800, increasing to 69% (95% CI 50-84; P = 0.027) with P400. Two patients had grade 4 toxicities with P800. The most common grade 3 toxicities were increased transaminases (16%), hypertension (13%), and diarrhea (9%) with P800, and gastrointestinal disorders (16%; 6% diarrhea) and hypertension (6%) with P400. Median follow-up was 47 months. Three-year recurrence-free survival was 76% (95% CI 65%-86%) with pazopanib and 83% (95% CI 74%-92%) with placebo [hazard ratio = 1.3 (95% CI 0.6-2.7), P = 0.53]. Five-year overall survival was 83% (95% CI 72-94) with pazopanib and 94% [95% CI 88-100] with placebo [hazard ratio = 1.8 (95% CI 0.6-5.5), P = 0.26]. CONCLUSIONS: In resected stage I NSCLC patients adjuvant 400 mg/day pazopanib but not 800 mg/day was feasible, although possibly infra-therapeutic and failed to improve relapse-free survival.

Management of malignant pleural mesothelioma: a French multicenter retrospective study (GFPC 0802 study).

BACKGROUND: Malignant pleural mesothelioma (MPM) is a rare disease with poor prognosis in spite of significant improvement in survival, due to new chemotherapy regimens. We describe here patients' profiles and management in daily practice in France. METHODS: Observational retrospective study. Data were collected from medical files. All patients with histologically proven MPM diagnosed from January 2005 to December 2008 were included in the participating sites. RESULTS: Four hundred and six patients were included in 37 sites: mean age 68.9 ± 9.8 years, male predominance (sex ratio 3.27), latency of the disease 45.7 years, epithelioïd type 83 %. Diagnosis was made using thoracoscopy in 80.8 % of patients. Radical surgery was performed in 6.2 % of cases. Chemotherapy was administered to 74.6 % of patients. First line regimens consisted mainly of platinum + pemetrexed (91 %) or pemetrexed alone (7 %). Objective response rate was 17.2 % and another 41.6 % of patients experienced disease stabilization. Half of these patients underwent second line chemotherapy (platinium + pemetrexed 31.6 %, pemetrexed alone 24.6 %), resulting in a 6 % response rate. Third-line chemotherapy (56 patients) yielded disease control in 5.4 % of cases. CONCLUSIONS: The management of MPM in France is usually in accordance with guidelines. Response rates are somewhat lower than those described in clinical trials.

Multicentre phase II study of cisplatin-etoposide chemotherapy for advanced large-cell neuroendocrine lung carcinoma: the GFPC 0302 study.

BACKGROUND: The optimal treatment of large-cell neuroendocrine carcinoma (LCNEC) of the lung remains unclear. Here, our primary objective was to assess the efficacy of cisplatin-etoposide doublet chemotherapy in advanced LCNEC. Accuracy of the pathological diagnosis and treatment toxicity were assessed as secondary objectives. PATIENTS AND METHODS: Prospective, multicentre, single-arm, phase II study with a centralised review of treatment-response and pathological data. Patients had untreated performance status (PS) 0/1 stage IV/IIIB LCNEC and received cisplatin (80 mg/m22 d1) and etoposide (100 mg/m22 d1-3) every 21 days. RESULTS: Eighteen centres included 42 patients (mean age, 59 ± 9 years; 69% men; median of four cycles/patient). At least one grade-3/4 toxicity occurred in 59% of patients (neutropaenia, thrombocytopaenia, and anaemia in 32%, 17%, and 12%, respectively). The median progression-free survival (PFS) and overall survival (OS) were 5.2 months (95% confidence interval, CI, 3.1-6.6) and 7.7 months (95% CI, 6.0-9.6), respectively. The centralised pathologist review reclassified 11 of 40 (27.5%) patients: 9 as small-cell lung cancer, 1 as undifferentiated non-small-cell lung cancer, and 1 as atypical carcinoid. Survival data were not significantly changed by excluding the reclassified patients. CONCLUSIONS: The pathological diagnosis of LCNEC is difficult. The outcomes of advanced LCNEC treated with cisplatin-etoposide doublets are poor, similar to those of patients with advanced small-cell lung carcinoma (SCLC).

Pemetrexed and cisplatin as first-line chemotherapy for advanced non-small-cell lung cancer (NSCLC) with asymptomatic inoperable brain metastases: a multicenter phase II trial (GFPC 07-01).

BACKGROUND: Brain metastases (BM) occur in up to 40% of non-small-cell lung cancer (NSCLC) patients. This trial assessed the safety and efficacy of pemetrexed-cisplatin in this population. PATIENTS AND METHODS: Chemonaive NSCLC patients with BM ineligible for (radio)surgery, performance status (PS) of 0 to 2, were eligible for up to six cycles of cisplatin 75 mg/m(2) and pemetrexed 500 mg/m(2) every 3 weeks. Whole -brain radiotherapy was given in case of disease progression or at chemotherapy completion. Primary end point was objective response rate (RR) on BM. Secondary end points included extracerebral and overall RR, safety profile and survival. RESULTS: Forty-three patients were enrolled. Initial characteristics were mean age 60.4 years; males 29; PS: 0 in 37.2%, 1 in 60.5% and 2 in 22.3% of patients; adenocarcinoma in 36 patients, large cell in 4 patients (nonsquamous, 93%) and squamous carcinoma in 3 patients. Functional classification of neurological status was stage I/II 86.0%, III 2.3% and IV 11.6%. Grade 3-4 hematological toxic effects were neutropenia, 11 patients (febrile neutropenia, 1 patient), and anemia, 6 patients. Non-hematological toxic effects were grade 2 urinary infection, one patient; grade 3 pneumonia, two patients; and grade 3 hypoacousia, one patient. Cerebral, extracerebral and overall RR by intent to treat analysis were 41.9%, 34.9% and 34.9%, respectively. Median survival time and time to progression were 7.4 and 4.0 months, respectively. CONCLUSION: Pemetrexed-cisplatin is an effective and well-tolerated regimen as first-line therapy for NSCLC patients with BM who always suffer a poor prognosis.

Molecular follow-up of first-line treatment by osimertinib in lung cancer: Importance of using appropriate tools for detecting EGFR resistance mutation C797S.

The C797S mutation encoded by EGFR exon 20 is classically observed as a tertiary event in EGFR-mutant non-small-cell lung carcinoma (NSCLC) primarily treated by first generation tyrosine kinase inhibitors (TKI) and secondarily treated by third-generation TKI, such as osimertinib, if the EGFR-T790M resistance mutation is detected. Recently, significant prolonged progression free survival has been observed following first-line osimertinib, in EGFR-mutant NSLC. While mechanisms of molecular resistance to first-generation TKI have been well studied, little is known about resistance induced by primary third-generation TKI treatments. We report the case of a 65 year-old female treated by first-line osimertinib for a multimetastatic exon 19-EGFR-mutant NSCLC. EGFR-C797S resistance mutation and PIK3CA mutation were detected together with the remaining EGFR-exon 19 deletion. This observation provides insights of acquired resistance to first line-osimertinib. It also highlights the importance of making molecular platforms which perform routine EGFR testing in lung cancer aware of the kind of therapeutic protocols given to the patient. Indeed, for rapid results or low-costs procedures, some targeted methods specifically targeting T790M may be used at relapse and may overlook alterations such as C797S or PIK3CA mutations. Targeted next generation sequencing is therefore a recommended option.

[An unusual development following anti-tuberculous treatment: Obstructive inflammatory granuloma]. / Une séquelle peu fréquente après traitement antituberculeux : l'obstruction granulomateuse inflammatoire.

Tuberculosis is a disease that is still a too frequent. Its treatment depends on prolonged, multi-antibiotic, chemotherapy. Progress following treatment is generally good but there is the possibility of parenchymatous or pleural sequelae such as bronchial stenosis due to post tuberculous bronchial fibrosis or bronchiolithiasis. On the other hand, bronchial obstruction after treatment by an inflammatory granuloma is rare. It causes wheezing dyspnoea. In this case, relapse of the tuberculosis was feared, possibly with the development of multi-drug resistance. Treatment with corticosteroids allowed a rapid improvement.

[A severe side effect of antitubercular therapy: pyrazinamide induced thrombocytopenia]. / Un effet indésirable grave du traitement antituberculeux: la thrombopénie au pyrazinamide.

The haematological side effects of antitubercular drugs are not well known. We report the observation of a patient who received Rifater for the treatment of pulmonary tuberculosis. After one month of treatment, he developed an acute pulmonary infection, with neutropenia (1218/microl) and thrombocytopenia (109,000/microl), requiring suspension of his antitubercular drugs. After the reintroduction of he again developed thrombocytopenia (6,000/microl) associated with bleeding and required treatment with intravenous immunoglobulin. The introduction of a combination of moxifloxacin, isoniazid, pyrazinamide, and ethambutol was followed by a new relapse of the thrombocytopenia. Responsibility of pyrazinamide was then suspected and later confirmed by the evolution of platelet levels after stopping and reintroducing this antibiotic. This is the third reported case of pyrazinamide induced thrombocytopenia, whose frequency is probably underestimated because of the use of compound treatment.

Randomized multicentric phase II study of carboplatin/gemcitabine and cisplatin/vinorelbine in advanced non-small cell lung cancer GFPC 99-01 study (Groupe français de pneumo-cancérologie).

PURPOSE: To evaluate the efficacy and safety of gemcitabine and carboplatin in the treatment of previously untreated patients with advanced non-small cell lung cancer (NSCLC). METHODS: A randomized phase II study was conducted by the Groupe Français de Pneumo-Cancérologie (GFPC) in 15 centers. The patients were randomized in either arm A (GC): gemcitabine 1250 mg/m2 on days 1 and 8+carboplatin AUC 6 mg/(mLmin) on day 1; or in arm B (VP): vinorelbine 30 mg/m2 weekly+cisplatin 80 mg/m2 on day 1. Treatment cycles were repeated every 3 weeks. RESULTS: A total of 100 patients were randomized with stage IV or stage III NSCLC with malignant pleural effusion: 51 patients in arm A and 49 patients in arm B. A total of 190 cycles were administered in the GC arm and 172 cycles in the VP arm, with a median of four cycles per patient in each arm. The dose intensity was 84.9% for gemcitabine, 99.8% for carboplatin, 97.7% for cisplatin and 67.7% for vinorelbine. The objective response rates were 19.6% (95% CI, 9.8-33.1) for GC and 29.2% (95% CI, 17.0-44.1) for VP in an ITT analysis. The response duration was 169 days in arm A and 226 days in arm B. The TTP was similar with 140 days (GC) and 148 days (VP), respectively. Overall survival rates were 334 days in the GC combination and 304 days in the VP combination. Overall, the treatment was safe and toxicities observed were different in each arm: neutropenia was the most common toxicity in the VP treatment, whereas thrombocytopenia was more frequent in the GC combination. Anemia was similar in both arms. Non-haematologic toxicity was mild. One toxic death in arm A and three toxic deaths in arm B were observed. CONCLUSION: In terms of response rate, the gemcitabine-carboplatin combination was not efficient enough to allow further phase III study. Survival data are in the same range as the standard arm. This chemotherapy is feasible and may represent an alternative to a standard cisplatin-based regimen, allowing treatment in an outpatient setting.

Comparison of racecadotril and loperamide in adults with acute diarrhoea.

METHODS: A multicentre, randomized, double-blind, double-placebo, parallel-group study was carried out to compare the efficacy, tolerability, and safety of racecadotril (100 mg three times daily) and loperamide (2 mg after each diarrhoeic stool) in 157 adults with acute diarrhoea. Patients were treated for 7 days or until recovery, if this took place earlier. RESULTS: Both groups of patients passed similar numbers (mean +/- S.E.M.) of stools before recovery (3.5 +/- 0.5 for racecadotril vs. 2.9 +/- 0.4 for loperamide), and the duration of diarrhoea (mean +/- S.E.M.) was similar in both groups (14.9 +/- 2.0 h for racecadotril and 13.7 +/- 2.2 h for loperamide). Both treatments reduced the incidence of associated symptoms and signs during the study, and both were similarly well tolerated. However, more patients on loperamide reported rebound constipation during treatment (18.7% vs. 9.8% with racecadotril). CONCLUSIONS: The enkephalinase inhibitor, racecadotril, and the intestinal transit inhibitor, loperamide, were similarly and rapidly effective in resolving the symptoms and associated signs of diarrhoea.

Comparison of racecadotril and loperamide in children with acute diarrhoea.

METHODS: A multicentre, parallel-group, double-blind, double-placebo study was carried out to compare the efficacy, tolerability, and safety of racecadotril and loperamide in children aged 2 to 10 years who were suffering from acute diarrhoea. Patients received racecadotril (1.5 mg/kg) or loperamide (0.03 mg/kg) three times daily plus matching placebo until recovery. Fifty-two children received racecadotril and 50 loperamide. RESULTS: Patients on racecadotril passed a mean (+/- S.E.M.) of 2.7 +/- 0.4 stools before recovery compared with 2.1 +/- 0.4 stools for loperamide. The duration of diarrhoea was similar with both treatments. The incidence of adverse events was lower with racecadotril than with loperamide (11.5% vs. 22%), and significantly more patients on loperamide suffered from constipation (58% vs. 36.5%; P = 0.03). Moreover, significantly more children receiving loperamide required concomitant medication during the study (38% v 19.2%; P = 0.047). Measurement of abdominal circumference at the final consultation, 6 days after entry to the study, revealed no significant differences between treatments. CONCLUSIONS: Racecadotril and loperamide were equally effective in treating acute diarrhoea in these children, and racecadotril had a superior tolerability and safety profile.

Racecadotril demonstrates intestinal antisecretory activity in vivo.

BACKGROUND: Racecadotril (acetorphan), a potent enkephalinase inhibitor, protects endogenous enkephalins from degradation. Racecadotril exhibits experimental and clinical antidiarrhoeal activity without any effect on intestinal motility, suggesting selective antisecretory activity. The antisecretory effect of racecadotril was directly assessed in the present study. METHODS: A 1 m, jejunal, Thiry-Vella loop was created in six mongrel dogs, and water and ionic fluxes were evaluated during infusion (2 mL/min) of Tyrode solution labelled with 14C-polyethylene glycol. Fluxes were determined both in the basal state and 5-6 h after commencement of a 2-h infusion of cholera toxin (0.4 microgram/mL). Racecadotril (10 mg/kg) or vehicle was given orally with and without prior intravenous administration of naloxone (0.1 mg/kg) or phentolamine (0.2 mg/kg). RESULTS: Basal absorption remained unchanged following racecadotril administration; however, racecadotril significantly decreased (P = 0.01) cholera toxin-induced water, sodium, and potassium hypersecretion, from 0.73 +/- 0.15 to 0.37 +/- 0.13 mL/min; from 125.0 +/- 16.1 to 14.7 +/- 9.5 microMol/min; and from 3.41 +/- 0.66 to 1.66 +/- 0.61 microMol/min, respectively. This antisecretory activity of racecadotril was suppressed by naloxone but not by phentolamine. CONCLUSIONS: This study directly demonstrates the antisecretory activity of racecadotril in relation to the protection of endogenous enkephalins.

Effects of racecadotril and loperamide on bacterial proliferation and on the central nervous system of the newborn gnotobiotic piglet.

METHODS: The effects of 4 days of oral administration of different doses of two drugs, an enkephalinase inhibitor (the antisecretory agent, racecadotril) and a mu-receptor agonist (loperamide), on intestinal growth of a bacterial nonpathogenic strain (Escherichia coli E 404) and on the central nervous system (CNS) were compared in newborn gnotobiotic piglets. RESULTS: The E. coli content of the proximal jejunum (segment S1) and the E. coli ratio of stomach:segment S1 were similar in the racecadotril (20 mg/kg b.d., n = 5) and control groups. In contrast, in the loperamide group (1 mg/kg b.d., n = 4), the E. coli content of segment S1 and the E. coli ratio stomach:S1 were both significantly higher than with racecadotril or control (P = 0.04 and 0.005, respectively, for E. coli content; P = 0.05 and 0.03, respectively, for stomach:S1). There were no clinical signs of neurotoxicity and no deaths with racecadotril given orally at a high dose of 130 mg/kg b.d. (n = 5)--nearly 60 times the paediatric dosage. In contrast, an equivalent high dose of loperamide (5 mg/kg b.d.) resulted in death in three out of four piglets. CONCLUSIONS: In contrast to loperamide, racecadotril did not induce bacterial overgrowth and did not produce central neurotoxicity.

Racecadotril versus placebo in the treatment of acute diarrhoea in adults.

METHODS: A two-centre, double-blind, parallel-group, randomized study was carried out to compare the efficacy and tolerability of racecadotril (100 mg three times daily) and placebo in 70 adult patients with acute diarrhoea. An objective criterion of antisecretory activity, stool weight, was used. RESULTS: Racecadotril produced a significant (P = 0.025) decrease in stool weight during the first day of treatment compared with placebo, and was also associated with significantly fewer diarrhoeic stools than placebo after 1 day of treatment (p = 0.027). Racecadotril and placebo were equally well tolerated, and the frequency of symptoms and signs was similar in both groups after 4 days of treatment. Fewer patients on racecadotril suffered from abdominal distension following treatment (5.6% vs. 18.2% on placebo). CONCLUSIONS: Racecadotril acts rapidly to resolve acute diarrhoea and has an incidence of adverse events similar to that of placebo.

Action of enkephalinase (EC 3.4.24.11) inhibition on the pre- and post-prandial electromyographic patterns of colon in rats.

Endogenous opioids are an important regulatory factor for the digestive tract and specially for its motility pattern. Enkephalin degradation includes an enkephalinase (EC 3.4.24. 11) and the effects on the colic electromyographic profile of its inhibition by acetorphan has been investigated in the unrestrained rat. Electromyogram consisted of Long Spike Bursts (LSB). In fasted state, they propagated indifferently in both aboral or oral directions from any point of the colon. Feeding privileges LSB which start near the cecal junction and propagated aborally to the distal colon. The acetorphan treatment (A) increases the percentage of LSB propagating aborally on the entire colon in fasted state and (B) reinforces the increased percentage of LSB which propagated down on the entire colon induced by feeding. All the actions of acetorphan on colic motility pattern disappear after inhibition of opioid receptors by naloxone. That may account for involvement of enkephalins in acetorphan properties on the pattern of the colic electrical activity.

Acetorphan prevents cholera-toxin-induced water and electrolyte secretion in the human jejunum.

OBJECTIVES: Acetorphan is an orally administered inhibitor of enkephalinase in the wall of the digestive tract. It prevents inactivation of endogenous opioid peptides released by submucosal and myenteric neurons. The aim of this study was to examine the effect of acetorphan on jejunal water and electrolyte transport in healthy volunteers under basal conditions and in a state of intestinal secretion induced by a bacterial enterotoxin. DESIGN: Ten volunteers in two groups were studied in an open trial. For the experimental design an intestinal perfusion technique was used. METHODS: Cholera toxin was used to induce intestinal secretion in a model employing segmental perfusion of the human proximal jejunum. Acetorphan was given orally prior to intrajejunal administration of cholera toxin; its effect on intestinal transport was measured over a period of four hours after exposure to cholera toxin. Serum levels of methylthioether of thiorphan as the main metabolite were measured throughout three experiments to assure sufficient drug absorption. RESULTS: Acetorphan had no influence on basal water and electrolyte absorption (133 vs. 140 ml/30 cm x h). In a control group with cholera toxin alone, significant water secretion was induced (131 ml/30 cm x h). Acetorphan completely prevented this secretion by leaving an absorption rate of 27 ml/30 cm x h. Intestinal electrolyte transport was also significantly changed towards absorption by acetorphan. CONCLUSION: Acetorphan can prevent jejunal water and electrolyte secretion induced by cholera toxin. Enkephalins may thus protect the small intestine from enterotoxin-induced secretion.

Treatment of refractory diarrhoea in AIDS with acetorphan and octreotide: a randomized crossover study.

OBJECTIVE: To compare the efficacy and tolerance of acetorphan, an orally active enkephalinase inhibitor whose antidiarrhoeal properties derive from a purely antisecretory activity, to that of octreotide, a subcutaneously administered somatostatin analogue, in the treatment of refractory diarrhoea in AIDS patients. DESIGN: An open randomized crossover trial. SETTING: The inpatient medical units of three hospitals. PATIENTS: Thirteen adult inpatients with AIDS and refractory diarrhoea that lasted for 35 +/- 8 weeks despite use of traditional antidiarrhoeal agents and was characterized by 7.0 +/- 1.2 stools/day, weighing 1033 +/- 174 g/day with a lipid output of 18.8 +/- 3.5 g/day. INTERVENTIONS: Acetorphan (100-300 mg thrice daily) and octreotide (50-150 micrograms thrice daily) were given in random order during two 1-week periods. MAIN OUTCOME MEASURES: Response was defined as a reduction by at least one-third of both daily stool number and weight. RESULTS: The mean daily stool number was reduced to 4.6 +/- 1.1 with acetorphan (P < or = 0.05) but was 5.6 +/- 1.2 with octreotide (NS). Whereas two patients responded to both treatments, two responded to acetorphan alone and one to octreotide alone. Daily lipid output in faeces was reduced non-significantly with acetorphan (11.5 +/- 2.3 g) but was nearly doubled with octreotide (33.7 +/- 12.0 g). Acetorphan was very well tolerated. CONCLUSION: Enkephalinase inhibitors may be a useful alternative to somatostatin analogues in the management of refractory diarrhoea in AIDS.

[Treatment of acute chemically induced diarrhea by inhibition of enkephalinase. Results of a pilot study]. / Traitement de la diarrhée aiguë chimio-induite par inhibition de l'enképhalinase. Résultats d'une étude pilote.

BACKGROUND AND OBJECTIVES: Acute chemotherapy-induced diarrhoea may require reducing or even stopping subsequent therapy. Antidiarrhoeal drug efficiency has not been extensively studied and the effects of the new antisecretory compound acetorphan--a potent enkephalinase inhibitor active in acute diarrhoea--are unknown. The aim of this study was to investigate the possible effects of acetorphan on 5 FU-induced diarrhoea in man. MATERIAL AND METHODS: Fifteen patients reporting acute diarrhoea following chemotherapy were included in this study. They presented with metastatic colo-rectal cancer (n = 14) or pancreatic carcinoma (n = 1) and were treated, once weekly, by an 8-hour IV infusion of folinic acid 200 mg/m2 and 5 FU 1,800 to 3,000 mg/m2. In each patient, number and consistency of stools were assessed every day during the week following chemotherapy, once without (control period) and once with acetorphan p.o. 300 mg/d/7d. RESULTS: During the control period, 3 out of 15 patients did not have significant diarrhoea, but 2 out of 3 patients had abdominal pain which was relieved by acetorphan without appearance of constipation. Twelve out of 15 patients presented with diarrhoea (> 3 stools/day for > 2 days: WHO grades 2 and 3); with acetorphan, the number of stools per day was reduced in all cases from 6.3 (range: 3-10.6) to 4.9 (range: 2.6-8.9) (P < 0.002), and the number of days with liquid stools dropped from 4.7 (range: 2-7) to 2.4 (range: 0-7) (P < 0.02). In addition, during treatment with acetorphan, there was a close positive linear relationship between the percent reduction in the number of stools and the number of stools during control period up to a 8 stools/day level (8 patients) above which efficiency decreased (4 patients). CONCLUSION: These results suggest the efficacy of acetorphan on chemotherapy-induced diarrhoea and urgent need for a randomized controlled trial.

[Immunodepression and pulmonary infections]. / Immunodépression et infections pulmonaires.

The acquired immunosuppressed states are increasingly numerous. Pneumopathies are a frequent, serious complication and etiologic diagnosis is often difficult. The nature of the micro-organism in question is a function of the immunizing type of deficiency. In neutropenias, the infections are primarily bacterial, their potential gravity being correlated with the depth of the deficiency into polynuclear, or fungic, especially in prolonged neutropenias. The aspleened states are responsible for a deficit of the macrophage system and contribute to the infections with encapsulated germs (pneumococci, klebsiellas...). The organic grafts imply an attack of cell-mediated immunity, in the particular case of the auxiliary T lymphocytes (CD4)), with a special predisposition for viral and fungic infections. During VIH infection, the immunizing deficit of CD4 lymphocytes worsens with time. At the early stage, the infections are especially bacterial. At the more advanced stages, the pulmonary pneumocystosis and tuberculosis dominate. At the late stage, finally, deep immunosuppression allows emerging of the atypical mycobacteries. In the deficiencies of humoral immunity (congenital hypogammaglobulinemias, lymphoid hemopathies B), the germs to be mentioned are the pneumococcus, Haemophilus influenzae, the salmonellas and the legionellas. Immunosuppressed pneumopathies are characterized by radio-clinical pictures of very variable gravity, ranging from focused acute pneumopathy to bilateral diffuse pneumopathy with acute respiratory distress syndrome, with phases of atypical tables with respiratory symptomatology larval or absent. The highlighting of the micro-organisms in question requires urgent complementary investigations: hemocultures, bronchiolo-alveolar washing. In certain cases, it will be possible to resort to the transtracheal puncture or transthoracic puncture guided by tomodensitometry, and if necessary to pulmonary biopsy under videothoracoscopy. Emergency of the anti-infectious treatment imposes, in general, a presumptive treatment directed according to the immunizing deficiency in question and etiologic suspicion. It will be associated, if necessary, with urgent measurements of respiratory intensive care.

[Disseminated histoplasmosis caused by Histoplasma capsulatum with cerebral involvement occurring 13 years after the primary infection]. / Histoplasmose disséminée à Histoplasma capsulatum avec atteinte cérébrale survenue 13 ans après la primo-infection.

A 49-year-old man with disseminated histoplasmosis (pulmonary and central nervous system involvement) successfully treated with ketoconazole and fluconazole combination is reported. Histoplasma capsulatum infection of the central nervous system is extremely rare in France partly because the organism is not endemic. Oral treatment with newer triazoles may be useful for central nervous system histoplasmosis, but additional information is needed to establish their effectiveness.

[40 cases of dengue (serotype 3) occurring in a military camp during an epidemic in New Caledonia (1989). The value of vector control]. / A propos de 40 cas de dengue (sérotype 3) survenus dans un camp militaire lors de l'épidémie de Nouvelle-Calédonie (1989). Intérêt de la lutte antivectorielle.

An epidemic of dengue occurred at the beginning of 1989 in New Caledonia. About 18 p.c. of the population was stricken (25,000 to 30,000 estimated clinical cases). The military camp of Plum was stricken too, but a prompt vector control was established. 8.6 p.c. of the strength was affected by classical dengue without severe hemorrhagic manifestations. Such prevalence is lower than the one rated in the civil population, demonstrating the major importance of vector control to limit spreading of such an epidemic as a tetravalent vaccine is not yet available.