Impact of protease inhibitors on AIDS-defining events and hospitalizations in 10 French AIDS reference centres. Fédération National des Centres de Lutte contre le SIDA.

OBJECTIVE: To assess the clinical and economic consequences of the use of protease inhibitors in the treatment of HIV infection. DESIGN: Multicentric, observational, retrospective cohort study. SETTING: Ten AIDS reference centres in France. PATIENTS: All patients followed in each centre from September 1995 through October 1996. MAIN OUTCOME MEASURES: AIDS-defining events, death, health-care resources use, administration of antiretroviral therapy. RESULTS: Data from 7749 patients in 10 centres showed a drop in hospitalization days by 35%, new AIDS cases by 35%, and deaths by 46%. In the same period, the proportion of patients receiving antiretrovirals rose from 36 to 53% including highly active antiretroviral therapy (HAART), which rose from 0.3 to 18%. Overall cost evaluation showed a slight increase of monthly treatment cost of US$ 12 per patient. Comparison of the three centres that used HAART earliest to the three centres that used it latest showed a clear benefit to early HAART with a drop in hospitalization days by 41%, new AIDS cases by 41% and deaths by 69%. The proportion of patients with HAART rose to 27% and monthly health-care cost decreased by US$ 248852 (i.e., by US$ 101 per patient per month). Late prescribing centres experienced a less marked effect with a drop in hospitalization days by 22%, new AIDS cases by 31%, and deaths by 32.5%. Proportion of patients with HAART rose to 12% and monthly health-care costs increased by US$ 113578 (i.e., by US$ 38 per patient per month). CONCLUSIONS: This study supports the extensive use of HAART in HIV-infected patients.

Opportunistic infections occurring during highly active antiretroviral treatment.

OBJECTIVE: To analyse the characteristics of opportunistic infections in patients receiving highly active antiretroviral treatment (HAART). DESIGN AND METHODS: A retrospective study performed in seven hospitals, included all patients starting treatment by ritonavir or indinavir between 26 March and 31 December 1996. Patients were evaluated for the development of AIDS-defining events. Clinical evaluation, plasma HIV-1 RNA quantification, CD4 cell count were recorded at baseline and at the onset of the event. RESULTS: Four hundred and eighty-six patients were included: 44.2% had a CD4 cell count below 50 x 10(6) cells/l. Fifty clinical events were recorded in 46 patients with a mean follow-up of 6.1 months, of which 34 events (68%) were observed during the first 2 months of HAART. Eighteen of these occurred despite a reduction of viral load by at least 1.5 log10) and a 100% increase of the CD4 cell count compared with that at the onset of the event, corresponding to 11 cytomegalovirus infections, five mycobacterial infections, one case of cryptococcosis, and one case of Varicella-Zoster virus-related acute retinal necrosis. Among the 16 events observed after the second month, six occurred despite a marked biological improvement, corresponding to a recurrence in five of six patients who had stopped their maintenance therapy. Events were one cytomegalovirus infection, two mycobacterial infections, one episode of oesophageal candidiasis and one cryptococcal meningitis. CONCLUSION: In patients at high risk of developing an opportunistic infection prior to the institution of a HAART regimen, prophylaxis should not be discontinued during the first 2 months of treatment, and maintenance therapy should be carried on despite a significant increase in the CD4 cell count.

Effect of endothelin-1 on corticosteroid secretion by the frog adrenal gland is mediated by an endothelinA receptor.

We have previously reported that endothelin-1 (ET-1) stimulates the in vitro secretion of corticosterone and aldosterone from the adrenal gland of the frog Rana ridibunda. The aim of the present study was to investigate the pharmacological profile of the endothelin receptor subtype involved in the corticotropic effect of ET-1. The mixed ET(A)/ET(B) receptor antagonist Ro 47-0203 (10(-5) M) totally blocked the stimulatory effect of ET-1 (5 x 10(-9) M) on corticosterone and aldosterone secretion. The action of ET-1 was also inhibited by the selective ET(A) receptor antagonist BQ-485 (10(-7) M). In contrast, the selective ET(B) receptor antagonist IRL 1038 (10(-6) M) did not affect the response of the frog adrenal gland to ET-1. In addition, the selective ET(B) receptor agonist IRL 1620 (10(-6) M) did not mimic the stimulatory effect of ET-1. The high affinity ET(C) receptor agonist endothelin-3 (ET-3) stimulated corticosteroid secretion, but was 400 times less potent than ET-1. Moreover, the action of ET-3 was also blocked by BQ-485 (10(-7) M). These data indicate that the stimulatory effects of ET-1 and ET-3 on corticosteroid secretion by the frog adrenal gland are mediated by an ET(A) receptor subtype.

Localization, identification, and action of galanin in the frog adrenal gland.

The distribution of galanin-like immunoreactivity was studied in the adrenal gland of the frog Rana ridibunda using the indirect immunofluorescence technique. A dense network of varicose fibers immunoreactive to galanin was found in the adrenal tissue. A combination of HPLC analysis and RIA detection was used to characterize galanin-like immunoreactivity in frog adrenal gland extracts. The elution profile revealed the existence of a single form of galanin exhibiting the same retention time as synthetic frog galanin. The possible involvement of galanin in the regulation of corticosteroid secretion was investigated in vitro using a perifusion system for frog adrenal slices. For concentrations ranging from 10(-9) to 3 x 10(-6) M, synthetic frog galanin induced a dose-dependent inhibition of corticosterone and aldosterone release. Repeated pulses of galanin (10(-6) M), given at 90-min intervals, resulted in a reproducible inhibition of corticosteroid secretion without any apparent tachyphylaxis. During prolonged administration of galanin (10(-6) M), the steroidogenic effect of ACTH (10(-9) M) was significantly reduced. In contrast, galanin did not attenuate the stimulation of corticosteroid secretion induced by the angiotensin II analog [Sar1,Val5]angiotensin II. These results show the occurrence of galanin in fibers innervating the frog adrenal gland. The data also demonstrate that synthetic galanin inhibits spontaneous and ACTH-induced corticosteroid release. Taken together, these findings suggest that galanin, released by nerve fibers in the adrenal tissue, can act locally as a modulator of steroid secretion.

The effect of the endozepine triakontatetraneuropeptide on corticosteroid secretion by the frog adrenal gland is mediated by activation of adenylyl cyclase and calcium influx through T-type calcium channels.

We have recently found that, in the frog adrenal gland, endozepines are present in chromaffin cells and we have shown that the triakontatetraneuropeptide TTN is a potent stimulator of corticosteroid secretion in vitro. In the present study, we have investigated the transduction mechanisms mediating the corticotropic effect of TTN on adrenocortical cells. Incubation of adrenal explants with graded concentrations of TTN induced a dose-dependent increase in cAMP formation, but did not affect polyphosphoinositide metabolism. Pretreatment of adrenal cells with the protein kinase A inhibitor H-89 markedly reduced the stimulatory effect of TTN on corticosterone and aldosterone secretion by perifused cells, whereas the phospholipase C inhibitor U-73122 did not affect the TTN-evoked stimulation of corticosteroid output. Incubation of adrenal cells with cholera toxin abolished the stimulatory effect of TTN on steroid secretion. Administration of a brief pulse of TTN (10(-6) M) in the vicinity of cultured adrenocortical cells induced a robust increase in the concentration of intracellular calcium ([Ca2+]i). Repeated pulses of TTN resulted in a gradual attenuation of the responses, indicating the existence of a desensitization phenomenon. Incubation of the cells with the T-type calcium channel blocker mibefradil significantly reduced the TTN-evoked [Ca2+]i increase, whereas the L-type calcium channel blocker nifedipine and the N-type calcium channel blocker omega-conotoxin GVIA had no effect. Incubation of adrenal cells with H-89 markedly reduced the stimulatory effect of TTN on [Ca2+]i. The involvement of calcium in steroid secretion induced by TTN has also been investigated. Administration of mibefradil significantly reduced the TTN-evoked stimulation of steroid production, whereas nifedipine was devoid of effect. Taken together, these data indicate that in frog adrenocortical cells, the endozepine TTN stimulates cAMP formation and calcium entry through T-type calcium channels. The effects of TTN on the adenylyl cyclase/protein kinase A pathway and calcium influx both contribute to the stimulatory action of the peptide on corticosteroid secretion.

Safety and efficacy of ritonavir and saquinavir in combination with zidovudine and lamivudine.

BACKGROUND: Ritonavir is a potent inhibitor of cytochrome P4503A4 that strongly increases saquinavir bioavailability. In this study we assessed the safety and antiretroviral efficacy of the combination of these two compounds in patients pretreated and receiving continued treatment with zidovudine and lamivudine who were protease inhibitor naive and who had a CD4 cell counts below 200/mm3. METHODS: In this 48-week pilot study, all patients received 600 mg ritonavir and 400 mg saquinavir twice daily. Administration of zidovudine and lamivudine was continued without a change in previous doses. Viral load, CD4 cell count, and the emergence of resistance to the two protease inhibitors were evaluated repeatedly up to week 48. RESULTS: Sixteen patients were included in the study. Previous nucleoside analog treatment duration was 48+/-22 months (mean +/- SD). Two patients quit taking both protease inhibitors within 2 weeks. The ritonavir dose had to be reduced in 10 other patients because of side effects. Between inclusion and week 48, plasma viremia varied from 4.87+/-0.43 to 3.00+/-1.29 log10 copies/mL and CD4 cell counts ranged from 98+/-61 to 250+/-139/mm3. Ten patients (63%) had viral loads below 200 copies/mL and 7 (44%) had viral loads below 50 copies/mL. A single key mutation that conferred ritonavir resistance I84V and V82A/V developed in two patients. A mutation at codon 54 developed in another patient. These mutations were associated with repeated cessations of antiretroviral treatment. No lipodystrophy was observed. CONCLUSION: Ritonavir and saquinavir in combination are quite well tolerated and induce a high and sustained antiretroviral efficacy. A four-drug combination that includes these two protease inhibitors should be considered as a first line of treatment in patients with low CD4 cell counts.

Occurrence and specificity of anti-B lymphocyte antibodies in renal allograft recipients.

Anti-HLA-A,B and anti-B lymphocyte antibodies were screened as part of a prospective alloimmunity monitoring study in 29 renal allograft recipients using a standard microlymphocytotoxicity test. Warm-reactive and/or cold-reactive lymphocytotoxins were directed against a panel of B lymphocytes, the donor's B lymphocytes, and the recipient's own B lymphocytes. A small proportion of patients had pretransplant antibodies, whereas about one-half of the patients had post-transplant antibodies. One-year allograft survival rates were lower among the patients with warm- and cold-reactive sera than among those with nonreactive sera or pure B cold-reactive sera. The sera of 20 patients were tested against donor B lymphocytes. The presence of donor-specific antibodies correlated closely enough with graft loss to be of predictive value. Autoantibodies appeared to have an enhancing effect in this study.

Longitudinal study of HIV-specific cytotoxic lymphocytes in HIV type 1-infected patients: relative balance between host immune response and the spread of HIV type 1 infection.

To evaluate the contribution of a specific cytotoxic response in the control of HIV infection in relation to clinical status, we performed serial analysis of anti-Env and anti-Gag cytotoxic activity in 13 infected individuals over a 6- to 10-year period, using cryopreserved peripheral blood mononuclear cells (PBMCs). Autologous EBV-transformed B cell lines infected in vitro with recombinant vaccinia viruses expressing HIV-1 env and gag genes were used as targets. Without any stimulation of the effector cells, we were able to show an anti-HIV cytotoxic activity in the PBMCs of 12 of 13 HIV-1-infected patients, consistent with chronic immune activation in HIV infection. Different patterns of HIV-specific cytotoxic activity were observed, and the extent of this cytotoxic response varied between the clinically defined groups of individuals. No direct relationship was observed with the number of CD4 and CD8 lymphocytes during the observation period. However, patients who remained asymptomatic had a more vigorous cytotoxic response than patients with clinical deterioration during the observation period, and a significant difference was observed for HIV Gag-specific CTL activity. From these data, we suggest that the HIV-specific cytotoxic response has a protective role in the course of HIV infection.

The stimulatory effect of endothelin-1 on frog adrenocortical cells is mediated through both the phospholipase C and the adenylyl cyclase transduction pathways.

We have previously shown that endothelin-1 (ET-1) stimulates corticosterone and aldosterone secretion by the frog adrenal gland through activation of ET(A) receptors. In the present study, we have investigated the transduction pathways involved in the corticotropic action of ET-1. Exposure of frog adrenal explants to ET-1 provoked a time- and dose-dependent increase in inositol phosphate production and a parallel decrease in membrane polyphosphoinositide content. Incubation of adrenal explants with ET-1 also induced a dose-related increase of cAMP formation. The selective ET(A) receptor antagonist BQ-485 totally abolished the stimulatory effects of ET-1 on both inositol phosphate and cAMP production. In contrast, the selective ET(B) receptor agonist IRL 1620 did not significantly modify polyphosphoinositide hydrolysis or cAMP formation. Administration of the phospholipase C inhibitor U-73122 or the protein kinase A inhibitor H-89 to perifused frog adrenal slices significantly reduced the stimulatory effect of ET-1 on corticosterone and aldosterone secretion. Concomitant administration of the two inhibitors almost completely suppressed the corticotropic effect of ET-1. Taken together, these data indicate that, in the frog adrenal gland, the stimulatory effect of ET-1 on corticosteroid secretion is mediated through activation of both the phospholipase C and the adenylyl cyclase transduction pathways.

Evidence for the involvement of nitric oxide in the control of steroid secretion by the frog adrenal gland.

Nitric oxide (NO) has been found to modulate the response of rat, bovine and human adrenocortical cells to corticotropic factors. The aim of the present study was to investigate the possible involvement of NO in the control of corticosteroid secretion in the frog Rana ridibunda. Histochemical studies using the NADPH-diaphorase reaction and immunohistochemical labeling with antibodies against NO synthase (NOS) revealed that NOS is exclusively expressed in chromaffin cells. The NO donor sodium nitroprusside (SNP) and the NO synthase inhibitor Nw-nitro-L-arginine (L-NO(2)Arg) did not modify the spontaneous production of corticosterone and aldosterone by perifused adrenal slices. Similarly, L-NO(2)Arg had no effect on the secretory responses induced by ACTH, angiotensin II (AII) and endothelin-1 (ET-1). In contrast, SNP significantly inhibited the stimulatory effects of ACTH, AII and ET-1 on corticosterone and aldosterone secretion. These data provide the first evidence for a modulatory role of NO on adrenocortical cell activity in amphibians.

New types of primers (stair primers) for PCR amplification of the variable V3 region of the human immunodeficiency virus.

The aim of the study was to develop a reliable PCR method for the detection of viral genomes with frequent mutations like HIV and hepatitis C virus. A system of 'stair' primers is suggested which allows amplification of a genomic sequence despite the presence of mutations in the region of the primers. In this system, classical primers are replaced with primers composed of a mixture of equimolar oligonucleotides in which the 5' end remains constant (single sized fragment) and the 3' end is displaced base by base. By PCR, 'stair' primers (HIV set) were compared to single-sequence primers of 20 and 25 nucleotides chosen in the same hypervariable region of the HIV gp120 (on both sides of V3 region), as well as to classical primers chosen in the conserved pol (polV2) and gag (SK38-39) regions of the genome. Of 17 HIV isolates obtained by co-culture of lymphocytes from HIV-seropositive patients, 17/17 (100%) were amplified using stair primers, 14/17 (82%) with 25-nucleotide primers, and 12/17 (70%) with 20-nucleotide primers. Amplification occurred in 17/17 instances with polV2 primers and in 16/17 instances with SK38-39. In addition, 55 other isolates were tested comparatively using stair, polV2 and SK38-39 primers. All isolates were amplified using stair and SK38-39 primers and 54/55 isolates with polV2 primers. When applied to 22 extracts of patients' lymphocytes DNA, stair primers amplified all 22 extracts to the same degree as polV2 and SK38-39, whereas the 20 and 25 nucleotide primers chosen in the variable region were not as reliable. This new primer system allows reliable detection of variable genomic regions of the HIV genome and amplification of such regions directly in patient leukocytes. In addition, the contribution of this system to microbiology and human genetics in general may be important.

Blood plasma fluoride in haemodialysed patients.

Blood plasma fluoride was determined in 15 chronic haemodialysed patients (60.2 +/- 7.2 yr old) before and after a 4-h dialysis using dialysates with very low fluoride level, and in two control groups, the first of 20 healthy younger subjects (45.9 +/- 3.4 yr old), the second of 8 healthy older subjects (69.1 +/- 6.8 y old). Before haemodialysis the fluoride concentration (1.31 +/- 0.31 mumol/l; 24.8 +/- 5.9 micrograms/l), was higher than in both control groups (0.35 +/- 0.16 mumol/l; 6.6 +/- 3.1 micrograms/l and 0.44 +/- 0.16 mumol/l 8.4 +/- 3.0 micrograms/l, respectively). During dialysis, the mean fluoride concentration fell to 0.94 +/- 0.26 mumol/l, remaining however, significantly higher than in control subjects. The use of fluoride-free dialysates seems to partially compensate the effect of renal impairment since plasma fluoride is only moderately increased in these patients.

Increase in blood plasma levels of boron and strontium in hemodialyzed patients.

Boron and strontium concentrations in blood plasma of controls and hemodialyzed patients from two Centers were determined by inductively coupled plasma emission spectrometry. Boron concentrations in blood plasma were respectively, in controls 2.6 +/- 0.9 mumol/l and in hemodialyzed patients 16.1 +/- 5.6 mumol/l before the dialysis session and 9.5 +/- 3.2 mumol/l at the end. The decrease in blood plasma during the dialysis was concomitant with an increase in the dialysis fluid (1.2 +/- 0.7 mumol/l at the beginning and 4.6 +/- 1.8 mumol/l at the end). Strontium concentrations in blood plasma were respectively, in controls 0.22 +/- 0.06 mumol/l and in hemodialyzed patients 0.62 +/- 0.24 mumol/l before the dialysis session and 0.64 +/- 0.14 mumol/l at the end. The mean concentration of strontium in the dialysis fluid was the same before (0.49 +/- 0.11 mumol/l) and after the dialysis session (0.49 +/- 0.10 mumol/l), but a transfer between plasma and dialysis fluid was shown by individual changes. Some considerations about these results are put forward but their possible clinical consequences are not yet known.

The presence of cytoplasmic antineutrophil cytoplasmic antibodies (C-ANCA) in the course of subacute bacterial endocarditis with glomerular involvement, coincidence or association?

Antineutrophil cytoplasmic antibodies positivity with cytoplasmic pattern (C-ANCA) and proteinase-3 (PR-3) specificity was found in two patients with both subacute bacterial endocarditis (SBE) and glomerular involvement. Renal biopsy showed membranoproliferative glomerulonephritis in one case and focal segmental glomerulonephritis in the second case. Immunofluorescence study showed granular immune deposits in both cases evocating immune complex glomerulonephritis. Renal and biological manifestations disappeared with clinical improvement secondary to antibiotherapy. Physicians have to consider the possible occurrence of such C-PR-3 ANCA, claimed to be specific markers for Wegener's granulomatosis, in infectious diseases such as SBE. Hence we focus on the necessity of performing a renal biopsy with light microscopy and immunofluorescence studies in all patients with ANCA associated glomerular disease.

[Progressive myoclonic encephalopathy in dialysis patients. Clinical, electroencephalographic and neuropathological study. Pathogenetic discussion]. / L'encéphalopathie myoclonique progressive des dialysés (E.M.P.D.). Etude clinique, électroencéphalographique et neuropathologique. Discussion pathogénique.

Clinical and Neuropathological data on sixteen cases of progressive myoclonic encephalopathy are reported. This neurological syndrome appears after an average duration of thirty two months of haemodialysis and leads to death in four and a half months, and is characterized by myoclonus, speech disorder, epileptic seizures, and mental-status changes. At first, clinical signs and symptoms are related to haemodialysis, later they become permanent. An early diagnosis is based on EEG which is the only useful laboratory test, demonstrating bisynchronous slow-wave bursts. The caracteristic histopathologic findings are neuronal depopulation, lipofuscin accumulation, and appearance of Neurofibrillary degeneration, especially in Motor cortex, red nucleus and dentato-olivary systems. It seems to be justified to attribute P.M.D.E. to aluminium chronic poisonning; the source of the aluminium intoxication is not aluminium containing phosphate-binding gels but intravenously administreted tape-water. The intracellular binding of aluminium is shown from a histochemical study employing fluorescent stain Morin.

[Water intoxication in psychiatric patients. 13 cases of severe hyponatremia]. / Intoxication par l'eau chez des malades psychiatriques. Treize épisodes d'hyponatrémie sévère.

Water intoxication mostly occurs in psychiatric patients. We observed 13 episodes of severe hyponatremia (less than 120 mmol/l) following a period of increased water consumption in 10 psychiatric patients (5 men, 5 women, mean age 48.8 years) treated with neuroleptics and/or benzodiazepines. Other causes of hyponatremia were excluded. The initial clinical signs were associated with severe gastrointestinal and neurological disorders requiring intensive care. In every case a gradual return to normal of natremia was obtained by creating a negative water balance while compensating for the sodium loss. From a study of urine and plasma osmolality ratio (U/P osm) on admission, several physiopathological mechanisms could be envisaged. A U/P osm ratio lower than 1 (6 cases) suggested a water intake exceeding the maximum dilution capacity of the kidneys (20-25 1), or a lesser water intake with little or no osmolal intake, or again an intrarenal disorder of urine dilution. When the U/P osm ratio was higher than 1 (7 cases), reflecting inappropriate secretion of the antidiuretic hormone, the hyponatremia could be explained by the psychosis itself, the treatment taken by the patients, a disorder of thirst regulation and/or a non-osmotic stimulation of vasopressin. This population, therefore, was heterogeneous: the mechanisms which contribute to this pathology are not fully elucidated, and they probably involve several factors.

[Renal failure during treatment with Ambisome]. / Insuffisance rénale au cours de traitements par AmBisome.

BACKGROUND: Although renal function is generally unaffected by liposome formulations of amphotericin B-deoxycholate, there is nevertheless a risk. CASE REPORTS: Two patients immunodepressed patients treated for candidosis involving the mouth and esophagus unresponsive to local care and flucanazol developed renal failure when given the liposome formulation of amphotericin B-deoxycholate (AmBisome). In one with normal renal function prior to treatment, moderate impairment was observed after initiating AmBisome. In the second patient, impaired renal function worsened after initiating treatment with amphotericin B-deoxycholate then progressed to very severe renal failure after switching to AmBisome. CONCLUSION: The indication for AmBisome (amphotericin B-deoxycholate treatment in patients with active renal impairment) must not overshadow the risk of worsening renal function under treatment.

[Changes in the plasma and erythrocyte concentrations of rubidium in patients with renal failure]. / Modifications des concentrations de rubidium plasmatique et globulaire chez les insuffisants rénaux.

Rubidium concentrations were measured by flame emission spectrophotometry in whole blood, plasma and red cells from male and female controls and from dialyzed and non-dialyzed patients of both sexes with chronic renal failure. Rubidium concentrations (mumol/l) in male and female controls respectively were: 2.29 +/- 0.29 and 1.96 +/- 0.46 in plasma: 36..79 +/- 5.90 and 30.19 +/- 6.11 in whole blood; 74.57 +/- 10.37 and 72.22 +/- 12.76 in erythrocytes. The red cell rubidium/plasma rubidium ratios were 32.6 in males and 38.3 in females. Compared with controls, dialyzed male and female patients showed, before dialysis, a decrease in rubidium concentrations of respectively -30% and -17% in plasma, -64% and -61% in whole blood, -40% and -33% in erythrocytes. A further decrease of 25% in rubidium plasma concentrations was observed after dialysis. Non dialyzed patients had an increase in plasma concentrations (+14% in males, +23% in females) and a decrease in erythrocyte concentrations (-16% in males, -20% in females) as compared with controls. Our data show that plasma and red cell rubidium concentrations are fairly constant and probably regulated in healthy subjects but vary considerably in patients with renal failure.

[Adult respiratory distress syndrome, a manifestation of severe pneumococcal infection]. / Le syndrome de détresse respiratoire de l'adulte, manifestation de l'infection pneumococcique grave.

A retrospective study analyzing the case notes of 49 hospitalized adults, either in intensive care (n = 26) or in thoracic medicine units (n = 23), for acute bacteriologically proven pneumococcal pneumonia based on samples obtained other than by sputum examination. The mortality was 54% in intensive care and 17% in the thoracic medicine unit. This significant difference may be explained in part by a respiratory distress syndrome in whom there were adequate criteria on admission for 7 patients in the intensive care group. Among these latter only one patient had had a splenectomy. The others did not have underlying disorders (three were chronic alcoholics); 7 patients were shocked on admission, four with a leukopenia less than 5,000/mm3 and six had a thrombocytopenia less than 100,000/mm3; finally 6 had a temperature of less than 38 degrees C. 7 patients died in less than four days (mean 2 days) in a clinical context of refractory hypoxemia. The significance of the respiratory distress syndrome is probably very different from the usual pneumonia; it seems rather to be an integration of the toxins induced by the pneumococcus. Its presentation can be particularly misleading as regards the diagnosis; the prescription of antibiotics once a diagnosis is obtained would seem insufficient by itself in this context to obtain a cure.

[Nosocomial urinary tract infection]. / Infection urinaire nosocomiale.

Care for asepsis and the use of a closed drainage system reduce the risk of urinary tract infection with indwelling catheter. Beyond a few days, infection will still end to occur, earlier in female and diabetic patients. Local or systemic antimicrobials have neither prophylactic nor even therapeutic actual usefulness, as long as infection remain asymptomatic, which is by far the most frequent situation. Thus, repeated cultures of urine samples are needless. Treatment should be applied to symptomatic infection. The risk for infection is lower in case of intermittent catheterization, with the use of a penilex or a percutaneous bladder catheter. Some instrumental procedures of surgical techniques require short-term antimicrobial prophylaxis: prostatic endoscopic resection, transperineal or transrectal prostatic biopsy, percutaneous nephrolithotomy, prostatectomy, cystectomy, prostheses implantation.