Elevated exhaled nitric oxide in patients with hepatopulmonary syndrome

The hypoxaemia of hepatopulmonary syndrome, seen in severe chronic liver dysfunction, occurs as a result of precapillary pulmonary arterial dilatation and arteriovenous communications. These abnormalities contribute to the mismatch between ventilation and perfusion, and the right to left blood flow shunting. Nitric oxide (NO) is a powerful vasodilator concerned with the regulation of pulmonary vascular tone in man. Using a chemiluminescence analyser, we have measured endogenously produced NO in the exhaled air of three patients with the hepatopulmonary syndrome, six normoxaemic cirrhotic patients and six healthy volunteers. The subjects breathed NO-free air throughout the measurements. The molar rate of production of exhaled NO was raised almost threefold in the patients with hepatopulmonary syndrome compared with normal volunteers and with normoxaemic cirrhotic patients. Hypoxia per se, achieved in the normal volunteers by breathing a hypoxic gas mixture, reduced rather than increased the exhaled NO. One hepatopulmonary syndrome patient received an orthotopic liver transplant and achieved normoxaemia after 3 months. The exhaled NO also returned to normal. Increased pulmonary production of NO could contribute to the development of the hepatopulmonary syndrome.     

The hepatopulmonary syndrome: radiologic findings in 10 patients

OBJECTIVE: The purpose of this study was to review the radiologic manifestations of the hepatopulmonary syndrome. MATERIALS AND METHODS: We retrospectively reviewed clinical records, chest radiographs, 99m Tc-macroaggregated albumin (MAA) perfusion lung scans, chest CT scans, and pulmonary angiograms of 10 patients with proven hepatopulmonary syndrome. RESULTS: Chest radiographs showed basilar, medium-sized (1.5-3.0 mm) nodular or reticulonodular opacities in all cases. CT was done in eight cases and showed basilar dilatation of lung vessels with a larger than normal number of visible branches. The vascular basis for these opacities was best appreciated on conventional CT scans of 10-mm sections. No individual arteriovenous malformations were seen on CT scans. High-resolution CT scans showed no evidence of interstitial fibrosis. 99mTc-MAA perfusion lung imaging, done in seven patients, showed pulmonary arteriovenous shunting in five. Contrast echocardiography confirmed intrapulmonary shunting in these five patients. Pulmonary angiography, done in four cases, showed subtle distal vascular dilatation in two and moderate dilatation with early venous filling in two but did not reveal any individual arteriovenous malformations. CONCLUSION: Chest radiographs in hepatopulmonary syndrome usually show bibasilar nodular or reticulonodular opacities. Conventional CT shows that these opacities represent dilated lung vessels. High-resolution CT is useful in excluding pulmonary fibrosis or emphysema as the cause of these opacities. 99mTc-MMA perfusion imaging or contrast echocardiography can be used to confirm intrapulmonary arteriovenous shunting.     

Response of the nose to exercise in healthy subjects and in patients with rhinitis and asthma

BACKGROUND: Although the nose and the bronchi are both involved in the process of regulating respiratory heat exchange, thermal changes may precipitate airway obstruction during exercise but rarely cause nasal obstruction in patients with rhinitis. The cause of the different response of the nose and bronchial tree has hardly been investigated. This study was performed to assess the response of the nose during exercise in the presence of rhinitis, asthma, and in normal controls. METHODS: Ten healthy subjects (group 1), 15 patients with asthma and rhinitis (group 2), 10 with rhinitis only (group 3), and 11 with asthma only (group 4) were included in the study. Exercise was performed on a bicycle ergometer for six minutes, reaching a heart rate of 80% of predicted. Bronchial and nasal responses were measured by forced expiratory volume in one second (FEV1) and posterior rhinomanometry, respectively. A drop in the FEV1 of 20% or more was considered a positive exercise induced asthma challenge test. RESULTS: Heart rate and ventilation increased by a similar proportion in the four groups. The FEV1 significantly decreased in asthmatic patients (groups 2 and 4) but it did not change in healthy subjects (group 1) or in those with rhinitis (group 3). Thirteen asthmatic patients developed exercise induced asthma. Nasal patency increased with exercise by a similar proportion in all groups, and no differences were detected between those with rhinitis (groups 2 and 3) and those without (groups 1 and 4). Nasal patency had returned to basal values at 25 minutes after completion of exercise in the four groups. The nose of patients with exercise induced asthma, however, remained significantly more patent than in patients without exercise induced asthma between 10 and 30 minutes after exercise. CONCLUSIONS: These results suggest that the nose responds differently from the bronchi during exercise induced airway obstruction: whereas the bronchial tree responds by becoming narrowed, the nose becomes more patent. These findings suggest that the mechanisms regulating the response of the nose to exercise are different from those involved in the response of the bronchial tree.     

Response to exercise in patients after repair of tetralogy of Fallot

Cardiac catheterization and submaximal exercise testing was performed in 38 patients after repair of tetralogy of Fallot (TF), and compared to 6 control patients who had functional murmurs. Cardiac index, heart rate, and stroke volume index were significantly lower in the TF group than in the control group. Right and left ventricular end-diastolic pressure increased significantly during exercise, which was not found in the control group. Total pulmonary vascular resistance (TPVR), which decreased significantly with exercise in the control group, did not change remarkably during exercise. TPVR was significantly higher in the TF group than in the control group both at rest and during exercise. Several factors were compared between patients with good cardiac index (> 5.0 l/min/m2; Group 1) and poor cardiac index (< 5.0 l/min/m2; Group 2) during exercise. Stroke volume index, right ventricular ejection fraction at rest were significantly higher in Group 1 than Group 2. TPVR, right and left ventricular end-diastolic and end-systolic volume index were significantly lower in Group 1 than in Group 2. There was no significant difference in heart rate, left ventricular ejection fraction, residual pulmonary stenosis, right to left ventricular systolic pressure ratio, and severity of pulmonary regurgitation between two groups. These findings indicate that abnormalities of exercise tolerance in patients after repair of TF were related to poor response of heart rate, pulmonary vascular resistance, and systolic and diastolic ventricular function.     

Interpretive algorithms for the symptom-limited exercise test: assessing dyspnea in Persian Gulf war veterans

The mechanisms by which respiratory syncytial virus (RSV) infection induces bronchiolitis and airway disease are unclear. The presence of large numbers of polymorphonuclear leukocytes (PMN) in the airways of infants with RSV infection suggests a potential role of PMN in airway injury associated with RSV infection. To investigate the potential role of neutrophils in RSV bronchiolitis, human alveolar type II cells (A549 cells) were infected with different doses of RSV for 6-48 h. A 51Cr-releasing assay was used to measure PMN-induced damage and image analysis was used to determine PMN adhesion and detachment of epithelial cells. The results showed that RSV infection of epithelial cells enhanced PMN adherence in a dose- and time-dependent pattern, RSV infection alone could damage and detach epithelial cells to a limited extent and PMN significantly augmented RSV infection-induced damage and detachment of epithelial cells. These data suggest that respiratory syncytial virus infection of respiratory epithelial cells enhances neutrophil adhesion to the epithelium and that activated neutrophils augment the damage and detachment of epithelium infected with the virus. Polymorphonuclear leukocytes may contribute to the pathogenesis of respiratory syncytial virus airway disease by inducing epithelial damage and cell loss.     

Cardiopulmonary exercise testing in the evaluation of patients with occupational asthma and reactive airways dysfunction syndrome

Oxidative stress has been known to play important roles in various inflammatory diseases of lung such as allergic bronchitis, dust particle-induced inflammatory diseases, or chronic bronchitis. However, the effects of oxidants on Cl- secretion in tracheal epithelia have not been determined. To examine the effects of oxidants on Cl- secretion of the airway epithelia rat tracheal epithelial cells were cultured on porous filters and short circuit current (Isc) was measured in an Ussing chamber system. t-Butylhydroperoxide, which was widely used as a model substance to study the mechanism of cell injury resulted from oxidative stress, induced a transient increase in Isc by dose-dependent manner. The response was not observed in Cl(-)-free medium, and inhibited by 100 microM bumetanide. N(-Diphenyl-1,4-phenylene-diamine (DPPD, 5 microM), an inhibitor of lipid peroxidation, blocked the t-butylhydroperoxide response. When t-butylhydroperoxide was added after the administration of forskolin or H-89, a protein kinase A inhibitor, the t-butylhydroperoxide-induce Isc increase was abolished. Pretreatment of indomethacin (10 microM) completely inhibited the t-butylhydroperoxide response, but pretreatment of thapsigargin (1 microM) did not, t-Butylhydroperoxide induced gradual increases in cytosolic Ca2+ level, and increased [3H]arachidonic acid release in the presence of thapsigargin. These results indicate that t-butylhydroperoxide stimulates Cl-secretion via activation of phospholipase A2 and subsequent production of cyclooxygenase metabolities by Ca(2+)-dependent and -independent mechanisms.     

Pressor response to isometric exercise in patients with multiple sclerosis

The purpose of this study was to determine whether patients with multiple sclerosis (MS) would show attenuated heart rate and/or pressor responses to isometric handgrip exercise. Patients with MS (30 males, 74 females, aged 23-61 yr) and control subjects (9 males, 16 females, aged 25-47 yr) performed isometric handgrip exercise at 30% of maximal voluntary contraction (MVC) to fatigue. Systolic, diastolic, and mean arterial pressure (MAP) increased linearly in both groups, but were significantly lower (P < 0.05) in patients with MS at 20%, 40%, 60%, 80%, and 100% of exercise duration. Mean change in MAP at fatigue was +47.9 mm Hg for controls and +28.2 mm Hg for patients with MS, with 18 patients with MS between -6 mm Hg and +15 mm Hg. Heart rate increased normally in patients with MS. To predict change in MAP at fatigue in patients with MS, stepwise regression analysis using six variables yielded an R2 of 0.26. These data suggest that in some patients MS lesions exist in areas of autonomic cardiovascular control that result in attenuated pressor responses to exercise. In 17% of patients tested, attenuation was profound. Data also suggest an abnormal dissociation between the heart rate and pressor response to static work in patients with MS.     

Different exercise performance between aged patients with syndrome X and those with coronary artery disease

In this review we survey the features of alcohol-induced lesions in the heart, in both the clinical and laboratory-animal setting. The data indicates a diverse range of lesions that contribute to the genesis of the entity alcoholic cardiomyopathy (also referred to as alcoholic heart muscle disease). Biopsies of affected patients reveal lesions similar to dilated cardiomyopathy though quantitative morphometry can distinguish between the two disorders. Biochemical analysis reveals an increase in the activities of some enzymes, though the pathogenetic nature of these alterations are unknown, but may well be adaptive. The induction of ischaemia in acute ethanol exposure may contribute to the heart muscle damage, though long term experimental studies indicate that heat shock proteins are reduced, making the heart more vulnerable to cardiac dysfunction. Changes in the rate of protein turnover induced by alcohol appear to be a central feature in animal studies and it is very likely that similar changes occur in man.     

Response to recombinant human erythropoietin in patients with myelodysplastic syndromes

OBJECTIVES: The impact of a positive surgical margin in otherwise confined prostate cancer after radical prostatectomy remains unclear. We analyzed the outcome of a large number of patients with organ-confined prostate cancer according to the presence and anatomic site of margin positivity. METHODS: We evaluated 2712 prostatectomy patients with Stage pT2N0 cancer (ie, no evidence of extra-prostatic disease, seminal vesicle or regional node involvement) and no prior therapy who were treated by radical prostatectomy between 1987 and 1995 at Mayo Clinic. A total of 697 patients (26%) had positive margins. To assess the effect of margin status in the absence of treatment, 378 patients with postoperative adjuvant therapy were not considered for the study group: the final group consisted of 2334 patients. RESULTS: Overall, 253 (58%) tumors were positive at the apex and/or urethra, 85 (19%) at the prostate base, 11 (2.5%) at the anterior prostate, and 174 (40%) at the posterior prostate; 89 (20%) had at least two margins involved and 21 (8.3%) had more than two involved. The apex/urethra was the only positive anatomic site in 183 (42%). Five-year survival free of clinical recurrence or prostate-specific antigen (PSA) biochemical failure (postoperative serum PSA of 0.2 ng/mL or more) for patients with a single positive margin was 79% for apex or urethra, 78% for anterior/posterior, and 56% for prostate base. Five-year survival free of clinical recurrence or PSA (biochemical) failure was slightly higher for those with one versus two margin-positive regions (77% versus 68%, respectively). Multivariate analysis revealed that positive surgical margins were a significant predictor of clinical recurrence and PSA (biochemical) failure (relative risk [95% confidence interval]: 1.65 [1.24, 2.18]) after controlling for Gleason grade, preoperative PSA, and deoxyribonucleic acid (DNA) ploidy. The effect of margin positivity on recurrence at a specific anatomic site (versus negative margins or positive at a different anatomic site) revealed the prostate base to be the only significant anatomic site when adjusted for grade, PSA, and ploidy. Five-year survival free of the combined clinical or PSA failure end point for those with versus those without positive margins at the prostate base was 56% versus 85%, respectively (P < 0.0001). CONCLUSIONS: Positive surgical margins are a significant predictor of recurrence in Stage pT2N0 cancer, which is independent of grade, PSA, and DNA ploidy. The impact of positive margin status on recurrence-free survival appears to be anatomic and site-specific, with prostate base positivity significantly associated with poor outcome. The benefit of adjuvant therapy based on anatomic site-specific margin positivity remains to be tested in order to optimize recurrence-free survival.     

Response to head-up tilt testing in patients with situational syncope

The results of head-up tilt testing were compared between 24 patients with situational syncope and 44 age-matched patients with typical vasovagal syncope. Patients with situational syncope showed poor positive responses, especially in the passive tilt results (8.3% vs. 39%, p = 0.0078).     

The role of endothelial nitric oxide synthase in the pathogenesis of a rat model of hepatopulmonary syndrome

BACKGROUND & AIMS: The hepatopulmonary syndrome occurs when intrapulmonary vasodilatation causes impaired arterial gas exchange in liver disease. The pathogenesis is poorly understood, although nitric oxide may be involved. Common bile duct ligation in the rat is a model of the hepatopulmonary syndrome, but no studies have evaluated NO in pulmonary vasodilatation in this model. The aim of this study was to determine whether NO contributes to intrapulmonary vasodilatation after bile duct ligation. METHODS: Endothelial and inducible NO synthase (NOS) levels and localization and NO activity in pulmonary artery rings were assessed after bile duct ligation. RESULTS: Pulmonary endothelial NOS levels increased and alveolar vascular staining was enhanced after bile duct ligation. No change in pulmonary inducible NOS levels or localization was detected. Increased endothelial NOS levels correlated with alterations in gas exchange and were accompanied by enhanced NO activity and a blunted response to phenylephrine, reversible by NOS inhibition, in pulmonary artery rings. Portal-vein-ligated animals, which do not develop intrapulmonary vasodilatation, had no changes in pulmonary NOS production or in NO activity in pulmonary artery rings. CONCLUSIONS: NO, derived from pulmonary vascular endothelial NOS, contributes to intrapulmonary vasodilation in animal hepatopulmonary syndrome.     

Mycobacteremia in patients with the acquired immunodeficiency syndrome

BACKGROUND: Bacillemia is a key event in the pathogenesis of tuberculosis. Although current evidence indicates that Mycobacterium tuberculosis bacteremia is rare in patients seronegative for the human immunodeficiency virus, it has been increasingly reported in patients with the acquired immunodeficiency syndrome (AIDS). OBJECTIVE: To determine clinical and laboratory characteristics of patients with AIDS and tuberculosis with and without bacillemia. METHODS: Fifty patients with AIDS with clinical suspicion of disseminated mycobacterial disease were prospectively selected. Three consecutive blood samples were collected for culture using a standardized protocol. RESULTS: Mycobacterium was isolated from any body site in 42 patients (84%). Bacillemia was detected in 30 (71.4%) of these 42 patients: 11 (28.2%) caused by Mycobacterium avium-intracellulare complex and 19 (71.8%) caused by M tuberculosis. Blood culture was the only method used to confirm the diagnosis in 5 (15%) of the 33 tuberculosis cases. Tuberculosis in patients with AIDS developed with nonspecific insidious symptoms, a remarkable elevated alkaline phosphatase level, and without the classic miliary radiological pattern. We could demonstrate 2 previously unrevealed clinical characteristics of bacteremic tuberculosis in patients with AIDS: a shift to the left in the white blood cell count and abdominal lymph node enlargement. In patients with tuberculosis, the in-hospital mortality rate was higher among patients with bacillemia, although the posttreatment survival rate was comparable. CONCLUSIONS: Blood culture is a valuable tool to confirm the clinical diagnosis of disseminated tuberculosis in patients with AIDS and can distinguish patients with characteristic clinical findings and outcome. Abdominal ultrasonography may be an additional helpful tool to identify these patients.     

Establishing mechanisms to conduct multi-institutional research--fatigue in patients with cancer: an exercise intervention

PURPOSES/OBJECTIVES: To describe the process of establishing a multi-institutional interdisciplinary team of oncology researchers and conducting a pilot study of an exercise intervention for fatigue. DATA SOURCES: Project meeting minutes and records, research team members' logs, subjects' research records, the research study proposal, and team members' individual and collective shared experiences. DATA SYNTHESIS: Site investigators established research teams at five academic medical centers. Fifty subjects were enrolled in the study and tested during their cancer treatment. Study methods, including instrumentation, were evaluated carefully and revised. CONCLUSIONS: The multi-institutional network of researchers is an effective and efficient model for testing an intervention to manage fatigue during cancer treatment. IMPLICATIONS FOR NURSING PRACTICE: Exercise is a feasible and potentially beneficial intervention to combat distressing cancer treatment-related fatigue. A pilot study is essential to determine the best methods for conducting a clinical trial and to develop the teams of researchers necessary for such a project.     

The growth hormone response to hexarelin in patients with Prader-Willi syndrome

Hexarelin (Hex) is a synthetic hexapeptide with potent GH-releasing activity in both animals and men. Aim of this study was to evaluate the GH response to a maximal dose of Hex and GH-releasing hormone (GHRH) in a group of patients with Prader-Willi syndrome (PWS). Seven patients (4 boys and 3 girls, age 2.4-14.2 yr) with PWS, 10 prepubertal obese children (7 boys and 3 girls, age 7.5-12.0 yr), and 24 prepubertal short normal children (11 boys and 13 girls, age 5.9-13 yr) with body weight within +/- 10% of their ideal weight were studied. All subjects were tested on two occasions with GHRH 1-29 at the dose of 1 microgram/Kg i.v., and with Hex at the dose of 2 micrograms/Kg i.v. In the PWS patients the GH response to GHRH (peak = 6.4 +/- 2.0 micrograms/l, p < 0.0001; AUC = 248 +/- 70 micrograms min/l, p < 0.0001) was significantly lower than that observed in the short normal children and similar to that observed in the obese children. In the PWS children the GH response to Hex (peak = 7.5 +/- 1.6 micrograms/l; AUC = 309 +/- 53) was similar to that observed after GHRH and significantly lower than that observed in the obese children (p < 0.05). The results of this study show that PWS patients have a blunted GH response to the administration of a maximal dose of Hex. Whether these findings reflect a more severe pituitary GH deficiency in PWS than in obese children or a deranged hypothalamic regulation of GH secretion need further investigation.     

EMG biofeedback to patients with Guillain-Barré syndrome.

Presents 4 cases in which electromyogram (EMG) biofeedback was used to improve upper extremity function in patients having Guillain-Barré syndrome. It is suggested that for those who experience recovery, biofeedback can enhance this natural process; for those who do not recover well, biofeedback may improve motoric status enough to provide greater independence and thereby enhance the quality of life. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Nutritional state and exercise tolerance in patients with COPD

We hypothesized that in patients with COPD, poor nutritional status adversely influences exercise tolerance by limiting aerobic capacity of exercising muscles. In 28 patients with stable COPD, we correlated nutritional status with gas exchange indexes obtained during maximal incremental cycle ergometer exercise and with respiratory function parameters. On the basis of percent of ideal body weight (%IBW), patients were divided into three groups (GP): GP1 (n = 8, %IBW < 90); GP2 (n = 13, %IBW > or = 90 < 110); and GP3 (n = 7, %IBW > or = 110). When compared with normally nourished individuals (GPs 2 and 3), malnourished GP1 patients showed greater reduction in maximal workload and in peak O2 uptake (VO2 peak), with earlier onset of metabolic acidosis (anaerobic threshold [AT]); in addition, indexes reflecting O2 cost of ventilation were higher in GP1. Nutritional status could be correlated with exercise tolerance (VO2 peak, r = 0.82, p < 0.0001), with onset of metabolic acidosis (AT, r = 0.69, p < 0.0001) and with dead space/tidal volume ratio (VD/VT, r = -0.59, p < 0.001). Body weight was inversely correlated with indexes that are likely to reflect the increase in O2 cost of ventilation. We conclude that in patients with stable COPD, (1) malnutrition significantly affects muscle aerobic capacity and exercise tolerance, and (2) high wasted ventilation and O2 cost of ventilation may be responsible for the weight loss.     

Analysis of impaired exercise capacity in patients with cirrhosis

Exercise limitation in cirrhosis is typically attributed to a cirrhotic myopathy (without impaired oxygen utilization) and/or a cardiac chronotropic dysfunction. We performed symptom-limited cardiopulmonary exercise testing in 19 cirrhotics without confounding variables (cardiopulmonary disease, beta blockade, anemia, smoking). Twelve concurrently exercised patients without cirrhosis and with normal resting pulmonary function were controls. Oxygen consumption (VO2) at peak exercise, at anaerobic threshold (VO2-AT), work rate (WR), and heart rate (HR) were measured. Cirrhotics had significantly lower peak WR (73+/-4 vs 107+/-7% predicted, p < 0.001), VO2 (72+/-4 vs 98+/-5% predicted, P < 0.001), VO2-AT (53+/-4 vs 71+/-5% predicted peak VO2, P < 0.01), HR (83+/-2 vs 91+/-2% predicted, P < 0.01) and were more likely to have chronotropic dysfunction (peak HR < 85% predicted). Six cirrhotics had normal aerobic capacity (peak VO2 > 80% predicted), while 13 were abnormal. The abnormals had an earlier AT (46+/-2 vs 67+/-3% predicted peak VO2, P < 0.05) but no difference in peak HR percent predicted was found. In conclusion, two thirds of cirrhotics, without confounding factors, have significantly reduced aerobic capacity. Cirrhotic myopathy (without impaired O2 utilization) and cardiac chronotropic dysfunction do not adequately account for the observed decrease in aerobic capacity.     

Response to beta blockers in patients with neurocardiogenic syncope: how to predict beneficial effects

No definitive data are available about the possibility of predicting improvement in patients with neurocardiogenic syncope treated with beta blockers. Among 112 patients with syncope and a positive head-up tilt test (HUT), independent predictors for prevention of symptoms with beta blockers were determined using the Cox proportional hazards model. Each patient underwent HUT at 70 degrees for 20 minutes both in the drug-free state and during isoproterenol infusion given to increase the heart rate by at least 25%. Fifty-nine patients had a positive HUT during isoproterenol infusion and 53 in the drug-free state. All patients were then given esmolol infusion at 500 micrograms/kg per minute for 3 minutes followed by 300 micrograms/kg per minute maintenance dose. HUT was then repeated as previously described with or without isoproterenol, depending upon the initial positive response. Regardless of the response during esmolol, all patients were treated with metoprolol 50 to 100 mg twice daily. At follow-up, 36 patients experienced symptom relapse. Four of them had negative HUT on esmolol, whereas the remaining 32 did not respond to the acute infusion of esmolol. Only four patients with positive HUT on esmolol had a favorable response to metoprolol. Patients responding to metoprolol were older (55 +/- 12 years vs 42 +/- 15 years, P < 0.05). Response to metoprolol was predicted by a negative test on esmolol (P < 0.0001) and a positive HUT on isoproterenol (P < 0.001). Age older than 42 years was also associated with a higher likelihood of metoprolol success (P < 0.02). CONCLUSION: Acute challenge with esmolol infusion appears to be an accurate predictor of response to chronic beta blockers, together with age and a positive HUT during low-dose isoproterenol infusion.     

Physical activity before and after exercise in women with chronic fatigue syndrome

Placenta growth factor (PlGF) is a homodimeric glycoprotein, 46-50 kDa in size, belonging to the vascular endothelial growth factor (VEGF) sub-family. It exists as two isoforms, PlGF-1 and -2, the latter having a heparin-binding domain. Like VEGF, it is a potent angiogenic factor; however, PlGF homodimers interact with the VEGF receptor Flt-1 (fms-like tyrosine kinase), but not with the kinase domain-containing region (KDR). Since PlGF is made by the human placenta and extravillous trophoblast (EV-T) cells of the human placenta express Flt-1 in situ, these cells may be responsive to PlGF. Therefore, this study examined whether first trimester EVT cells propagated in vitro expressed the mRNA or the protein of Flt-1 and PlGF, and whether exogenous PlGF-1 had any effect on EVT cell proliferation, migration or invasiveness. Immunocytochemical and RT-PCR analyses revealed that both normal and SV40 Tag-immortalized EVT cells expressed the protein and mRNA for Flt-1, but not for PlGF-1 or -2. Exogenous PlGF-1 stimulated proliferation (measured by 3H-thymidine uptake) of normal EVT cells in a concentration-dependent manner, but only in the presence of excess heparan sulphate proteoglycans (HSPGs). These results raise two possibilities: that exogenous PlGF-1 (in spite of having a low affinity for heparin) was sequestered away from its receptor because of binding to heparan sulphate proteoglycans on the EVT cell surface or the ECM, or that HSPGs could modify the interaction between Flt-1 and PlGF. PlGF-1, in the presence or absence of HSPGs, however, had no effect on EVT migration or invasiveness, when measured with a transwell invasion (in the presence of Matrigel) or migration (in the absence of Matrigel) assay. These findings place PlGF amongst a large group of growth factors that promote EVT cell proliferation without influencing their migratory or invasive behaviours, and suggest that PlGF-Flt-1 interactions may be regulated by HSPGs in situ.     

Septic shock in patients with the acquired immunodeficiency syndrome

OBJECTIVE: To evaluate the prognosis of patients with septic shock admitted to an intensive care unit (ICU), according to their HIV serostatus. DESIGN: Retrospective study. SETTING: Medical ICU of a university hospital. PATIENTS: 76 patients with septic shock admitted to the same ICU, of whom 28 were HIV positive and 48 were HIV negative. MEASUREMENTS AND RESULTS: Severity scores, number and type of organ failures, and survival rates were assessed in the two groups of patients. Glasgow Coma Scale and general severity scores [Acute Physiology and Chronic Health Evaluation II and Simplified Acute Physiology Score (SAPS)] were significantly worse in HIV-infected patients. The total number of organ failures was also higher in the HIV-positive group: 3.7 +/- 0.2 vs 3.1 +/- 0.2 in the HIV-negative group (p < 0.001). On day 28, 21 (46%) HIV-negative patients were dead compared to 26 (93%) patients in the HIV-positive group (p < 0.001). In the multivariate analysis, HIV infection was an independent risk factor for mortality, as were the SAPS score, use of mechanical ventilation, and the McCabe score. CONCLUSIONS: This study reports a considerable excess mortality in HIV-infected patients with septic shock. Although severity of illness was clearly much more pronounced in HIV-positive patients, retroviral infection was independently associated with death. Improving survival in HIV-positive patients with septic shock may require earlier diagnosis and treatment of the causative infection.