Delayed Diagnosis of a Diffuse Invasive Gastrointestinal Aspergillosis in an Immunocompetent Patient.

Invasive aspergillosis represents a clinical picture frequently associated with host's immunosuppression which usually involves a high morbidity and mortality. In general, the most frequent fungal entry is the lungs with secondary hematogenous dissemination, but there are other hypotheses like a gastrointestinal portal of entry. There are some rare publications of cases with invasive aspergillosis in immunocompetent patients. We present the case of an immunocompetent patient without any risk factors except for age, ICU stay, and surgical intervention, who developed a septic shock by invasive gastrointestinal aspergillosis as primary infection. Due to the unusualness of the case, despite all the measures taken, the results were obtained postmortem. We want to emphasize the need not to underestimate the possibility for an invasive aspergillosis in an immunocompetent patient. Not only pulmonary but also gastrointestinal aspergillosis should be taken into account in the differential diagnosis to avoid a delay of treatment.

Combined therapy with saquinavir, ritonavir and stavudine in moderately to severely immunosuppressed HIV-infected protease inhibitor-naive patients.

OBJECTIVE: To assess the short-term and long-term effect of a combination of saquinavir, ritonavir and stavudine in moderately to severely immunosuppressed protease inhibitor-naive patients. DESIGN: Prospective open-label multicentre study. PATIENTS AND METHODS: A total of 64 protease inhibitor-naive and stavudine-naive HIV-infected patients with a CD4 count of < 250 cells/microL and > 10 000 HIV-1 RNA copies/mL received saquinavir hard-gelatin capsules, ritonavir and stavudine. Full (drop in viraemia of > 2 log10 and/or < 500 copies/mL) and partial responders (drop to between 500 and 5000 viraemia copies/mL) at week 9 (end of phase I) entered the second phase (additional 12-month period). RESULTS: Fifty-six patients completed phase I, 45 (70%) full responders and nine (14%) partial responders by intent-to-treat analysis. Thirty-nine patients completed phase II, 33 (52%) full responders and two (3%) partial responders. Six patients had < 50 HIV-1 RNA copies/mL at week 9, and 20 (31%) patients at month 12 of phase II. Mean CD4 cell counts increased significantly in the 56 patients from 89 to 184 cells/microL after 9 weeks and from 100 to 292 cells/microL in the 39 patients treated for another 12 months. Higher baseline viraemia and lower baseline CD4 cell counts were not associated with an unfavourable virological response at week 9 and month 12 of phase II. HIV DNA in peripheral blood monocytes decreased substantially (- 1.5 log10) but was detectable in all except one patient at the end of phase II. CONCLUSION: In protease- and stavudine-naive HIV-infected patients with moderate to severe immunosuppression, saquinavir in combination with ritonavir and stavudine caused a substantial long-term decrease in plasma viral load in approximately half the participants and a substantial increase in CD4 cell counts.

CD14 expression on monocytes and TNF alpha production in patients with septic shock, cardiogenic shock or bacterial pneumonia.

OBJECTIVES: In patients with septic shock, circulating monocytes become refractory to stimulation with microbial products. Whether this hyporesponsive state is induced by infection or is related to shock is unknown. To address this question, we measured TNF alpha production by monocytes or by whole blood obtained from healthy volunteers (controls), from patients with septic shock, from patients with severe infection (bacterial pneumonia) without shock, and from patients with cardiogenic shock without infection. MEASUREMENTS: The numbers of circulating monocytes, of CD14+ monocytes, and the expression of monocyte CD14 and the LPS receptor, were assessed by flow cytometry. Monocytes or whole blood were stimulated with lipopolysaccharide endotoxin (LPS), heat-killed Escherichia coli or Staphylococcus aureus, and TNF alpha production was measured by bioassay. RESULTS: The number of circulating monocytes, of CD14+ monocytes, and the monocyte CD14 expression were significantly lower in patients with septic shock than in controls, in patients with bacterial pneumonia or in those with cardiogenic shock (p < 0.001). Monocytes or whole blood of patients with septic shock exhibited a profound deficiency of TNF alpha production in response to all stimuli (p < 0.05 compared to controls). Whole blood of patients with cardiogenic shock also exhibited this defect (p < 0.05 compared to controls), although to a lesser extent, despite normal monocyte counts and normal CD14 expression. CONCLUSIONS: Unlike patients with bacterial pneumonia, patients with septic or cardiogenic shock display profoundly defective TNF alpha production in response to a broad range of infectious stimuli. Thus, down-regulation of cytokine production appears to occur in patients with systemic, but not localised, albeit severe, infections and also in patients with non-infectious circulatory failure. Whilst depletion of monocytes and reduced monocyte CD14 expression are likely to be critical components of the hyporesponsiveness observed in patients with septic shock, other as yet unidentified factors are at work in this group and in patients with cardiogenic shock.

Prospective randomized comparison of imipenem-cilastatin and piperacillin-tazobactam in nosocomial pneumonia or peritonitis.

Nosocomial pneumonia and acute peritonitis may be caused by a wide array of pathogens, and combination therapy is often recommended. We have previously shown that imipenem-cilastatin monotherapy was as efficacious as the combination of imipenem-cilastatin plus netilmicin in these two settings. The efficacy of imipenem-cilastatin is now compared to that of piperacillin-tazobactam as monotherapy in patients with nosocomial pneumonia or acute peritonitis. Three hundred seventy one patients with nosocomial pneumonia or peritonitis were randomly assigned to receive either imipenem-cilastatin (0.5 g four times a day) or piperacillin-tazobactam (4.5 g three times a day). Three hundred thirteen were assessable (154 with nosocomial pneumonia and 159 with peritonitis). For nosocomial pneumonia, clinical-failure rates in the piperacillin-tazobactam group (13 of 75 [17%]) and in the imipenem-cilastatin group (23 of 79 [29%]) were similar (P = 0.09), as were the numbers of deaths due to infection (6 in the imipenem-cilastatin group [8%], 7 in the piperacillin-tazobactam group [9%]) (P = 0.78). For acute peritonitis, clinical success rates were comparable (piperacillin-tazobactam, 72 of 76 [95%]; imipenem-cilastatin, 77 of 83 [93%]). For infections due to Pseudomonas aeruginosa, 45 patients had nosocomial pneumonia (21 in the piperacillin-tazobactam group and 24 in the imipenem-cilastatin group) and 10 had peritonitis (5 in each group). In the patients with nosocomial pneumonia, clinical failure was less frequent in the piperacillin-tazobactam group (2 of 21 [10%]) than in the imipenem-cilastatin [corrected] group (12 of 24 [50%]) (P = 0.004). Bacterial resistance to allocated regimen was the main cause of clinical failure (1 in the piperacillin-tazobactam group and 12 in the imipenem-cilastatin group). For the patients with peritonitis, no difference in clinical outcome was observed (five of five cured in each group). The overall frequencies of adverse events related to treatment in the two groups were similar (24 in the piperacillin-tazobactam group, 22 in the imipenem-cilastatin group). Diarrhea was significantly more frequent in the piperacillin-tazobactam group (10 of 24) than in the imipenem-cilastatin group (2 of 22). This study suggests that piperacillin-tazobactam monotherapy is at least as effective and safe as imipenem-cilastatin monotherapy in the treatment of nosocomial pneumonia or peritonitis. In P. aeruginosa pneumonia, piperacillin-tazobactam achieved a better clinical efficacy than imipenem-cilastatin, due to reduced development of microbiological resistance. Tolerance was comparable, with the exception of diarrhea, which was more frequent with piperacillin-tazobactam.

Cytokines, nitrite/nitrate, soluble tumor necrosis factor receptors, and procalcitonin concentrations: comparisons in patients with septic shock, cardiogenic shock, and bacterial pneumonia.

OBJECTIVES: To determine and compare the respective concentrations of tumor necrosis factor (TNF)-alpha, interleukin (IL)-6, soluble TNF receptors, nitrite/nitrate (NO2-/NO3-), and procalcitonin in the plasma of patients with septic shock, cardiogenic shock, and bacterial pneumonia without shock; and to assess the predictive value of these mediators in defining patients with septic shock. DESIGN: Cohort study, comparing normal volunteers (controls) and patients with septic shock, cardiogenic shock, and bacterial pneumonia. SETTING: A collaborative study among an intensive care unit, an emergency room, and three research laboratories. PATIENTS: Mediators were measured at various times in 15 patients with septic shock (during the shock phase and during the recovery phase), in seven patients with cardiogenic shock during the shock phase, and in seven patients with severe bacterial pneumonia on day 1 of admission. INTERVENTIONS: Blood samples were collected at various times during the course of the disease. MEASUREMENTS AND MAIN RESULTS: TNF-alpha values were highest in the acute phase of septic shock (53 to 131 pg/mL during septic shock), while patients with bacterial pneumonia had intermediate concentrations (32 pg/mL). TNF-alpha concentrations were normal in patients with cardiogenic shock. IL-6 concentrations were highest in patients with acute septic shock (85 to 385 pg/mL). However, in contrast to TNF-alpha concentrations, IL-6 concentrations were normal in patients with bacterial pneumonia and increased in patients with cardiogenic shock (78 pg/mL). Soluble TNF receptors were increased in all three groups vs. controls, with the highest increase in patients with septic shock. NO2-/NO3- concentrations were highest (72 to 140 mM) in patients with septic shock, and were < 40 mM in the other groups of patients. Procalcitonin concentrations were only markedly increased in patients with septic shock (72 to 135 ng/mL, compared with approximately 1 ng/mL in the three other groups). The best predictive value for septic shock was found to be the measurements of NO2-/NO3- and procalcitonin concentrations. CONCLUSIONS: These observations showed that increase of proinflammatory cytokines was a consequence of inflammation, not of shock. In this study comparing various shock and infectious states, measurements of NO2-/NO3- concentration and procalcitonin concentration represented the most suitable tests for defining patients with septic shock.

[Psychiatric morbidity in the medical service of a non-university general hospital]. / Morbidité psychiatrique dans le service de médecine d'un hôpital général non universitaire.

The aim of this study was to assess the nature and extent of psychiatric pathology in the internal medicine service of a small general hospital. During a three months' period, 315 consecutive patients were enrolled in this prospective study. 92 persons (29% of the admitted patients) exhibited a psychiatric disorder which was recognized by the internists and then discussed with the psychiatric team. The disorders were diagnosed according to the DSM-III-R classification. The age of the patients with psychiatric disorders was lower (median 56 years versus 63 years) and women were more numerous. In 75% of cases the psychiatric problem influenced medical management. A psychiatric consultation was indicated in 12%. Concerning the nature of this pathology, 29% of the 120 diagnoses established in these 92 patients were linked to the use of psychoactive substances; alcohol and male sex predominated. Among the women, anxio-depressive and personality disorders predominated. Two-thirds of the patients were sent to a general practitioner following their discharge from the hospital. The role of the general hospital as a site of care for these patients is discussed. It can be considered positive if a good climate of cooperation exists with the psychiatric team.

[Probability of dying in an avalanche]. / Sterbewahrscheinlichkeit in einer Lawine.

Of 1,036 people caught in an avalanche and completely buried the burial time and whether they were recovered dead or alive is recorded. The data are used to calculate the likelihood to die in the avalanche as a function of the burial time, using Turnbull's non-parametric method. The result is compared with Brugger's et al for 332 cases. Furthermore the influence on the likelihood of mortality is investigated using further indications to reduce the time interval during which the victim has died.

Protein turnover and thermogenesis in response to high-protein and high-carbohydrate feeding in men.

The rates of energy expenditure and wholebody protein turnover were determined during a 9-h period in a group of seven men while they received hourly isocaloric meals of high-protein (HP) or high-carbohydrate (HC) content. Their responses to feeding were compared with those to a short period of fasting (15-24 h). The 9-h thermic response to the repeated feeding of HP meals was found to be greater than that to the HC meals (9.6 +/- 0.6% vs 5.7 +/- 0.4% of the energy intake, respectively, means +/- SEM, p less than 0.01). The rate of whole-body nitrogen turnover over 9 h increased from 17.6 +/- 2.2 g on the fasting day to 27.4 +/- 1.4 g during HC feeding (NS) and there was a further increase to 58.2 +/- 5.3 g resulting from HP feeding (p less than 0.001). By using theoretical estimates (based upon ATP requirements) of the metabolic cost of protein synthesis, 36 +/- 9% of the thermic response to HC feeding and 68 +/- 3% of the response to HP feeding could be accounted for by the increases in protein synthesis compared with the fasting state.

Hemodynamic effects of amrinone in children after cardiac surgery.

The hemodynamic effects of amrinone were assessed in seven children following cardiac surgery. Amrinone was administered as a bolus of 1 mg kg-1 body wt., followed by continuous infusion at 10 micrograms kg-1 min-1 for 1 h and two stepwise increases to 20 and 40 micrograms kg-1 min-1 for 30 min each. Hemodynamic data were obtained and plasma concentrations of amrinone measured 1 h after the bolus dose and immediately before each increment of the infusion rate. Amrinone levels ranged from 0.7 to 2.3 mg l-1. Administration of amrinone lowered systemic vascular resistance from 20.0 +/- 4.3 to 16.5 +/- 4.6 mmHg l-1 min-1 m-2 (p less than 0.05) and reduced mean arterial pressure from 71.7 +/- 9.5 to 62.6 +/- 13.5 mmHg (p less than 0.05) at the highest infusion rate, confirming the known vasodilative effect of the drug. However, these effects did not result in a statistically significant increase in stroke volume (35.0 +/- 7.5 to 35.5 +/- 7.0 ml m-2, NS) or cardiac index (3.10 +/- 0.50 to 3.20 +/- 0.40 l min-1 m-2). One additional patient, in whom a higher loading dose was tried in order to achieve a higher plasma concentration, developed systemic hypotension. A correlation was established between the plasma concentrations of amrinone and the percentage decrease in systemic resistance (r = 0.70, p less than 0.05). These results suggest that in children after open heart surgery, amrinone acts primarily as a systemic vasodilator, with questionable inotropic effect. Accordingly, its use should be restricted to children with severe cardiac failure and documented highly elevated afterload.

Chronotropic and inotropic supports are both required to increase cardiac output early after corrective operations for tetralogy of Fallot.

To assess the respective roles of chonotropism, inotropism, and afterload reduction in increasing cardiac index early after corrective operations for tetralogy of Fallot, we measured vascular pressures and cardiac output and evaluated left ventricular dimension changes before and after a 35% rise in heart rate over baseline. This rise was induced by atrial pacing with intact atrioventricular conduction, isoproterenol, or atrial pacing together with dobutamine. With atrial pacing, left ventricular end-diastolic diameter decreased (38.7 +/- 4.3 to 34.2 +/- 5.6 mm, p less than 0.05), the shortening fraction (ratio of the difference between left ventricular end-diastolic and end-systolic diameters to left ventricular end-diastolic diameter) remained constant, and stroke volume index was reduced (28.8 +/- 4.5 to 19.7 +/- 4.6 ml/m2, p less than 0.05). As a result, cardiac index was left unchanged. When dobutamine was added as supplemental inotropic support, left ventricular end-diastolic diameter remained constant, shortening fraction increased (30% +/- 5.4% to 36% +/- 3.3%, p less than 0.05), and cardiac index rose significantly (3.04 +/- 0.61 to 4.18 +/- 0.85 L/min/m2, p less than 0.05). Heart rate acceleration with isoproterenol, combining chronotropism, positive inotropic support, and afterload reduction, slightly increased left ventricular end-diastolic diameter, significantly raised shortening fraction, and markedly enhanced cardiac index (3.03 +/- 0.55 to 4.9 +/- 1.09 L/min/m2). Atrial pacing with intact atrioventricular conduction, as an isolated chronotropic stimulus, is not suited to increase cardiac index early after operations for tetralogy of Fallot unless additional inotropic support is simultaneously provided.

Propranolol treatment in children with tetralogy of Fallot alters the response to isoprenaline after surgical repair.

When propranolol is given to prevent hypoxaemic episodes in children with tetralogy of Fallot who are awaiting operation it is advisable to continue the treatment until shortly before the induction of anaesthesia. Because catecholamines are often required to maintain adequate cardiac output after surgical correction the effect of preoperative treatment with beta blockers on the response to isoprenaline after the operation was investigated in nine children given propranolol before operation and nine who were not. They were studied three and 24 hours after cardiopulmonary bypass. The haemodynamic response to increasing doses of infused isoprenaline was monitored. Immediately after cardiopulmonary bypass the response to isoprenaline was significantly blunted in the patients who had been given propranolol before operation. Their dose-response curve lay to the right of that for patients not given propranolol, and this indicates competitive inhibition. Propranolol concentrations in the blood and myocardium correlated significantly with the heart rate response to isoprenaline. Twenty four hours after operation the isoprenaline response was similar in both groups and concentrations of propranolol in the blood were minimal or undetectable. beta Blockers given up to the time of operation significantly altered the postoperative response to catecholamines.

Hemodynamic effect of isoprenaline and dobutamine immediately after correction of tetralogy of Fallot. Relative importance of inotropic and chronotropic action in supporting cardiac output.

In order to compare the effect of isoprenaline and dobutamine immediately after correction of tetralogy of Fallot, 12 randomly selected patients were studied postoperatively. Left ventricular end-diastolic volume, measured preoperatively by means of left ventricular angiograms in eight patients, was decreased to a mean value of 58.6 +/- 5.5 ml/m2 (mean +/- standard error of the mean). Postoperatively, cardiac output was measured by thermodilution before, during, and after infusion of increasing doses of isoprenaline (0.05, 0.1, and 0.2 micrograms/kg/min) and dobutamine (2.5, 5, and 10 micrograms/kg/min) successively given in each patient. Simultaneously, central venous, left atrial, pulmonary arterial, and systemic arterial pressures were recorded. Cardiac index increased significantly in response to all three doses of isoprenaline. Dobutamine produced only a small increase which was not statistically significant. Stroke volume index did not vary significantly with either drug. Consequently, cardiac index was directly related to heart rate. Preload of the left ventricle as well as afterload was significantly reduced (p less than 0.01 and p less than 0.05, respectively) by isoprenaline but not by dobutamine. An increase in left ventricular work index per minute was found with both drugs; however, only with isoprenaline was the increased work accompanied by a significant increase in cardiac index. We conclude that patients with tetralogy of Fallot usually have a small left ventricle which, immediately after correction, reacts to catecholamines by only an insignificant increase in stroke volume index. Consequently, isoprenaline is more effective than dobutamine in raising cardiac index due to the increase in heart rate. Moreover, it decreases systemic vascular resistances and obviates the need for administration of a vasodilator.