Chlamydia psittaci: a relevant cause of community-acquired pneumonia in two Dutch hospitals.

BACKGROUND: Of all hospitalised community-acquired pneumonias (CAPs) only a few are known to be caused by Chlamydia psittaci. Most likely the reported incidence, ranging from of 0% to 2.1%, is an underestimation of the real incidence, since detection of psittacosis is frequently not incorporated in the routine microbiological diagnostics in CAP or serological methods are used. METHODS: C. psittaci real-time polymerase chain reaction (PCR) was routinely performed on the sputum of 147 patients hospitalised with CAP, who participated in a clinical trial conducted in two Dutch hospitals. In 119/147 patients the paired complement fixation test (CFT) was also performed for the presence of Chlamydia antibodies. Positive CFTs were investigated by micro- Immunofluorescence for psittacosis specificity. Case criteria for psittacosis were a positive PCR or a fourfold rise of antibody titre in CFT confirmed by micro- Immunofluorescence. Furthermore, we searched for parameters that could discriminate psittacosis from CAPs with other aetiology. RESULTS: 7/147 (4.8%) patients were diagnosed with psittacosis: six with PCR and one patient with a negative PCR, but with CFT confirmed by micro- Immunofluorescence. Psittacosis patients had had a higher temperature (median 39.6 vs. 38.2 °C;) but lower white blood cell count (median 7.4 vs. 13.7 x 109/l) on admission compared with other CAP patients. CONCLUSION: In this study, C. psittaci as CAP-causing pathogen was much higher than previously reported. To detect psittacosis, PCR was performed on all CAP patients for whom a sputum sample was available. For clinical use, PCR is a fast method and sputum availability allows genotyping; additional serology can optimise epidemiological investigations.

Effect of a high monounsaturated fatty acids diet and a Mediterranean diet on serum lipids and insulin sensitivity in adults with mild abdominal obesity.

BACKGROUND AND AIMS: Diets high in monounsaturated fatty acids (MUFA) such as a Mediterranean diet may reduce the risk of cardiovascular diseases by improving insulin sensitivity and serum lipids. Besides being high in MUFA, a Mediterranean diet also contains abundant plant foods, moderate wine and low amounts of meat and dairy products, which may also play a role. We compared the effects of a high MUFA-diet with a diet high in saturated fatty acids (SFA) and the additional effect of a Mediterranean diet on insulin sensitivity and serum lipids. METHODS AND RESULTS: A randomized parallel controlled-feeding trial was performed, in 60 non-diabetics (40-65 y) with mild abdominal obesity. After a two week run-in diet high in SFA (19 energy-%), subjects were allocated to a high MUFA-diet (20 energy-%), a Mediterranean diet (MUFA 21 energy-%), or the high SFA-diet, for eight weeks. The high MUFA and the Mediterranean diet did not affect fasting insulin concentrations. The high MUFA-diet reduced total cholesterol (-0.41 mmol/L, 95% CI -0.74, -0.09) and LDL-cholesterol (-0.38 mmol/L, 95% CI -0.65, -0.11) compared with the high SFA-diet, but not triglyceride concentrations. The Mediterranean diet increased HDL-cholesterol concentrations (+0.09 mmol/L, 95% CI 0.0, 0.18) and reduced the ratio of total cholesterol/HDL-cholesterol (-0.39, 95% CI -0.62, -0.16) compared with the high MUFA-diet. CONCLUSION: Replacing a high SFA-diet with a high MUFA or a Mediterranean diet did not affect insulin sensitivity, but improved serum lipids. The Mediterranean diet was most effective, it reduced total and LDL-cholesterol, and also increased HDL-cholesterol and reduced total cholesterol/HDL-cholesterol ratio.

The maximal tolerable intravenous dosage of pentoxifylline in AIDS patients does not inhibit lipopolysaccharide-stimulated tumor necrosis factor alpha production.

Tumor necrosis factor alpha (TNF-alpha) may be involved in the pathogenesis of metabolic and endocrine changes in HIV infection. Pentoxifylline (PTX) is able to suppress the production of TNF-alpha in vitro. The effect of two dosages of intravenously administered PTX on clinical symptoms and ex vivo LPS-stimulated TNF-alpha production was evaluated in six clinically stable AIDS patients in a saline-controlled study. PTX in a dosage of 1.5 mg/min was tolerated without side effects. PTX in a dosage of 2.1 mg/min resulted in intolerable nausea and necessitated termination of infusion after 30 min. The average plasma concentration of PTX after infusion of 1.5 mg/min for 6 hr was 510+/-56 ng/ml, which is considerably below the concentrations that have been reported to suppress TNF-alpha production in vitro. No effect of PTX infusion (1.5 mg/min) on LPS-stimulated TNF production ex vivo was found. Our conclusion is that the maximally tolerated i.v. dosage of PTX in AIDS patients is 1.5 mg/min. LPS-stimulated ex vivo TNF-alpha production, at the LPS concentrations tested, was not inhibited by the plasma concentration of PTX that could be achieved at this dosage.

In vitro production of cytokines in whole blood versus plasma concentrations of cytokines in AIDS.

Reports on plasma concentrations of tumor necrosis factor alpha (TFN-alpha), interleukin 6 (IL-6), IL-10, and IFN-alpha in AIDS patients are contradictory. An alternative approach for the estimation of cytokine production is the measurement of lipopolysaccharide (LPS)-stimulated cytokine production in whole blood. We compared plasma concentrations of these cytokines, soluble TNF receptor (sTNFr) types I and II, and LPS-stimulated cytokine production in whole blood from clinically stable AIDS patients (n = 6) and healthy controls (n = 6). The plasma concentrations of TNF-alpha and sTNFr-II were higher in AIDS patients compared with controls (mean [95% CL]: TNF-alpha, 24 [17-31] and 8 [1-16] pg/ml, respectively, p < 0.01; sTNFr-II, 6.8 [4.6-9.0] and 3.2 [2.4-4.0] ng/ml, respectively, p < 0.01). The plasma concentrations of sTNFr-I and IL-10 were not different between AIDS patients and controls. Neither IL-6 nor IFN-alpha was detectable in any plasma sample. LPS-stimulated production in whole blood of TNF-alpha, IL-6, IL-10, and IFN-alpha was not different between AIDS patients and controls at any combination of LPS concentration (0, 0.1, 0.5, 1, 10, 100, and 1000 ng/ml) and duration of stimulation (0, 4, 8, and 24 hr). It is concluded that the plasma concentrations of TNF-alpha and sTNFr-II, but not of IL-6, IL-10, IFN-alpha, and sTNFr-I, are higher in AIDS patients compared with controls. The production of cytokines in LPS-stimulated whole blood does not provide information additional to the measurements of plasma concentrations.

Total energy expenditure in human immunodeficiency virus-infected men and healthy controls.

Total daily energy expenditure (TEE) has been reported to be slightly decreased in weight-stable acquired immune deficiency syndrome (AIDS) patients. This conclusion is based on a comparison of TEE measurements to the data reported by others. We measured TEE in nine weight-stable human immunodeficiency virus (HIV)-infected homosexual men (Centers for Disease Control [CDC]-II to -IV) without active opportunistic disease and nine age-, sex-, and height-matched healthy controls using the doubly labeled water technique for 2 weeks, and resting energy expenditure (REE) using the ventilated-hood technique. TEE in HIV-Infected patients was not significantly different from that in healthy controls (221 +/- 12.5 and 210 +/- 9 kJ.kg lean body mass [LBM]-1.d-1, respectively, NS). REE was approximately 10% higher in HIV patients than in healthy controls (134 +/- 4 and 125 +/- 4 kJ.kg LBM-1.d-1, respectively, P = .02). The energy spent in relation to physical activity was not different between HIV-Infected patients and the controls (66 +/- 10 and 64 +/- 5 kJ.kg LBM-1.d-1, respectively, NS). In conclusion, REE is increased by about 10% in weight-stable HIV-infected men without active opportunistic disease. TEE and the energy spent during physical activity are not different in this group of patients versus healthy controls. This is in contrast to the previously reported decrease of TEE in weight-losing AIDS patients. Therefore, the energy requirements of stable HIV-infected patients are not decreased compared with those of healthy subjects.

Lipolytic sensitivity to catecholamines in patients with human immunodeficiency virus infection.

Lipolysis is higher in patients with acquired immunodeficiency syndrome (AIDS) than in healthy control subjects. To evaluate whether this increase in lipolysis is related to increased beta-adrenergic sensitivity, we compared the lipolytic response to epinephrine (approximately 15 ng x kg(-1) x min(-1)) of six AIDS patients with that of six matched control subjects. Lipolysis was measured by infusion of [2H2]glycerol and [2H2]palmitate. The baseline rates of appearance of palmitate (2.06 +/- 0.21 compared with 1.45 +/- 0.07 micromol x kg(-1) x min(-1)) and glycerol (2.35 +/- 0.16 compared with 1.35 +/- 0.06 micromol x kg(-1) x min(-1)) were higher in AIDS patients (P < 0.05). The absolute increase in lipolysis, an indicator of the responsiveness to epinephrine, was not different between groups for the rate of appearance of palmitate (86 +/- 14 compared with 75 +/- 7 micromol x L(-1) x min(-1)) or glycerol (79 +/- 13 compared with 59 +/- 6 micromol x L(-1) x min(-1)). Plasma concentrations of epinephrine were not different between groups. Lipolysis was higher whereas the lipolytic response to epinephrine was normal in AIDS patients. Increased lipolytic sensitivity to catecholamines is not the cause of increased lipolysis in AIDS.

Effects of interferon-alpha (IFN-alpha) administration on leucocytes in healthy humans.

Plasma concentrations of IFN-alpha are increased in several inflammatory conditions. Several lines of evidence indicate that IFN-alpha has anti-inflammatory properties. To study the effects of IFN-alpha on leucocyte subsets and activation and on cytokines, we administered IFN-alpha (rhIFN-alpha2b; 5 x 10(6) U/m2) to eight healthy human subjects in a randomized controlled cross-over study and analysed changes in circulating leucocytes and parameters for neutrophil and monocyte activation. After administration of IFN-alpha, neutrophil counts increased, monocyte counts decreased transiently, whereas the number of lymphocytes, basophils and eosinophils showed a sustained decrease. IFN-alpha administration was also associated with neutrophil activation, reflected in an increase in the plasma concentrations of elastase-alpha1-antitrypsin complexes and lactoferrin. Serum neopterin, a marker for monocyte activation, was significantly increased 10 h after administration of IFN-alpha. IFN-alpha significantly increased plasma concentrations of IL-6, IL-8 and IL-10. Although IL-1 and tumour necrosis factor (TNF) remained undetectable, plasma concentrations of soluble TNF receptors p55 and p75 increased after IFN-alpha administration. We conclude that IFN-alpha induces multiple alterations in the distribution and functional properties of leucocytes. IFN-alpha exerts pro- as well as anti-inflammatory effects within the cytokine network.

Circadian growth hormone secretion in asymptomatic human immune deficiency virus infection and acquired immunodeficiency syndrome.

Although anabolic effects of GH supplementation have been reported in acquired immune deficiency syndrome (AIDS) patients, the effects of human immunodeficiency virus (HIV) infection per se on GH secretion are unknown. Therefore, we evaluated the characteristics of GH secretion in eight asymptomatic HIV-infected men, eight clinically stable male AIDS patients, and eight healthy controls. Wasting AIDS patients were not included to circumvent the confounding effects of opportunistic disease on GH secretion. Samples for GH analysis were taken at 10-min intervals over 24 h. GH was measured by immunoradiometric assay (detection limit, 0.08 mU/L). Insulin-like growth factor I (IGF-I) and IGF-binding protein-3 were measured every 6 h. The pulsatile secretion of GH was evaluated by Cluster and DESADE analyses. No differences in number of peaks, peak amplitude, peak length, peak interval, or GH secretion per 24 h were found among the studied groups. IGF-I and IGF-binding protein-3 concentrations were not different among groups. Circadian GH secretion in asymptomatic HIV infection and AIDS without wasting is not different from that in healthy subjects. Therefore, anabolic effects documented in clinical trials with recombinant human GH in AIDS patients are not merely explained by alterations in the GH/IGF-I axis induced by HIV infection per se.

Endocrine and metabolic effects of interferon-alpha in humans.

Interferon-alpha (IFN alpha) concentrations are increased in conditions associated with tissue injury. To investigate the endocrine and metabolic actions of IFN alpha in vivo, we studied eight healthy controls on two occasions, once after administration of 5 million units/m2 rhIFN alpha and once after administration of saline (control). Rates of appearance (Ra) of glucose and glycerol in plasma were measured by infusion of [3-3H]glucose and D5-glycerol, respectively. Energy expenditure and substrate oxidation were determined by indirect calorimetry. IFN alpha induced increases in plasma concentrations of norepinephrine (225 +/- 93%; P < 0.02 vs. control), epinephrine (272 +/- 80%; P < 0.05), cortisol (353 +/- 63%; P < 0.02), glucagon (50 +/- 12%; P < 0.05), free fatty acids (223 +/- 61%; P < 0.02), and glycerol (68 +/- 21%; P < 0.02) and in resting energy expenditure (36 +/- 50%; P < 0.03). The Ra of glycerol (169 +/- 39%; P < 0.02) and fat oxidation (104 +/- 23%, P < 0.02) were also increased after IFN alpha treatment. The Ra of glucose was higher at the end of the recombinant human IFN alpha treatment day than in the control experiment (12.83 +/- 1.08 vs. 9.34 +/- 0.46 mumol/kg.min; P < 0.03). It is concluded that IFN alpha administration induces, directly or indirectly, major endocrine and metabolic changes and is probably part of the cytokine network mediating the endocrine and catabolic reactions to tissue injury.