Plasma level of soluble urokinase-type plasminogen activator receptor as a predictor of disease severity and case fatality in patients with bacteraemia: a prospective cohort study.

OBJECTIVES: Urokinase-type plasminogen activator receptor (uPAR) is expressed on a variety of different immune cells and vascular endothelial cells during inflammation. Previous studies indicate that a high plasma concentration of the soluble form of the receptor (suPAR) predicts poor outcome in infectious diseases. DESIGN: A prospective cohort study. SUBJECTS AND METHODS: Plasma suPAR levels were measured in 132 patients with bacteraemia caused by Staphylococcus aureus, Streptococcus pneumoniae, ß-haemolytic streptococcae or Escherichia coli using a commercial enzyme-linked immunosorbent assay (ELISA). Values were measured on days 1-4 after a positive blood culture, on days 13-18 and on recovery. RESULTS: The maximum suPAR values on days 1-4 were markedly higher in nonsurvivors compared to survivors (15.8 vs. 7.3 ng mL(-1) , P < 0.001) and the area under the receiver operating characteristic curve (AUC(ROC) ) in the prediction of case fatality was 0.84 (95% confidence interval (CI) 0.76-0.93, P < 0.001). At a cut-off level of 11.0 ng mL(-1) , the sensitivity and specificity of suPAR for fatal disease was 83% and 76%, respectively. A high level of suPAR (≥ 11 ng mL(-1) ) was associated with hypotension (mean arterial pressure < 70 mmHg) (odds ratio (OR) 6.5; 95% CI 2.9-14.6) and high sequential organ failure assessment score (≥ 4) (OR 9.3; 95% CI 4.0-21.9). A high suPAR level remained an independent risk factor for case fatality in a logistic regression model adjusted for potential confounders. CONCLUSION: Plasma suPAR level is a sensitive and specific independent prognostic biomarker in patients with bacteraemia.

Genetics of C-reactive protein and complement factor H have an epistatic effect on carotid artery compliance: the Cardiovascular Risk in Young Finns Study.

Atherosclerosis is characterized by a prominent inflammatory component and C-reactive protein (CRP) has been implicated to modulate the complement activity in atherosclerotic arteries via complement factor H (CFH) binding. In this study, we examined whether the gene-gene interactions between CRP haplotypes and CFH Tyr402His functional polymorphism exerted an effect on early atherosclerosis. Single nucleotide polymorphisms (SNPs) in CFH (Tyr402His) and CRP (-717A>G, -286C >T>A, +1059G>C, +1444C>T and +1846G>A) were genotyped in the participants of the Cardiovascular Risk in Young Finns Study (n=1698, aged 24-39 years). The CRP SNPs were further constructed into haplotypes and their interactive effects with the CFH Tyr402His polymorphism on the early atherogenic vascular changes [i.e. carotid artery compliance (CAC) and intima-media thickness (IMT)] were examined. After risk factor adjustment, a significant gene-gene interaction (P=0.007) on CAC was observed between CRP haplotype ATGTG and CFH Tyr402His polymorphism in males. Furthermore, logistic regression analysis verified the risk-modifying interactive effect on CAC between these loci (OR 3.70, 95% CI 1.37-10.02, P=0.010). No effects on CAC were observed in females and no effects on IMT were detected in either sex. We conclude that the combined presence of CRP haplotype ATGTG and CFH 402His allele may be disadvantageous to carotid artery elasticity in males.

CRP and FCGR2A genes have an epistatic effect on carotid artery intima-media thickness: the Cardiovascular Risk in Young Finns Study.

The role of the inflammatory mediator C-reactive protein (CRP) in atherosclerosis is recognized although its specific functions are not entirely clear. CRP binds to the Fcgamma receptor2A (FcgammaR2A) and its polymorphism, FCGR2A (Arg131His), strongly influences the binding. We wanted to evaluate the CRP-mediated proatherogenic process on early atherosclerosis and investigated whether CRP and FCGR2A show an interactive effect on carotid intima-media thickness (IMT). Polymorphisms of FCGR2A (Arg131His) and CRP (-717A > G, -286C > T > A, +1059G > C, +1444C > T and +1846G > A) were genotyped and their effects on IMT were analyzed in 2260 young adults participating in the Cardiovascular Risk in Young Finns Study. CRP haplotypes were constructed based on the CRP polymorphisms. The FCGR2A(Arg131His) polymorphism did not have an independent effect on IMT but a significant gene-gene interaction, epistasis, between FCGR2A and CRP genetics on IMT was found. The epistatic effect was seen in men at haplotype and genotypic level; both CRP haplotype GCGCG (-717, -286, +1059, +1444 and +1846) and CRP-717A > G polymorphism interacted with FCGR2A(Arg131His) on IMT. After adjustment with classical risk factors the P-values for interaction were P = 0.013 and P = 0.010, respectively. No associations were observed in women. In conclusion, this study showed that the effect of CRP genetics on early atherosclerotic changes is modulated by the FCGR2A genetics.

Interaction between CD14-159C>T polymorphism and Helicobacter pylori is associated with serum total immunoglobulin E.

BACKGROUND: Total serum IgE is regulated by both environmental and genetic factors. Association and linkage studies have suggested a role of CD14-159C>T polymorphism in the regulation of serum total IgE, but the results have been contradictory. It seems that gene-environment interactions are involved in this regulation. OBJECTIVE: The aim of this study was to examine the possible gene-environment interactions among Toxoplasma gondii, Helicobacter pylori, CD14-159C>T and Toll-like receptor (TLR) 4+896A>G polymorphism on serum total IgE. For this study, we expanded the scope of our earlier comparison of allergic sensitization and microbial load between Finland and Russian Karelia by studying the CD14-159C>T and TLR4+896A>G polymorphism in a cohort of Russian Karelian children. METHODS: For this study, CD14-159C>T and TLR4+896A>G polymorphisms were analysed in 264 healthy Russian Karelian children. Serum total IgE levels and H. pylori and T. gondii antibodies were also measured. RESULTS: We constructed a multiway anova model to analyse the gene-environment interactions among T. gondii seropositivity, H. pylori seropositivity, CD14-159C>T and TLR4+896A>G polymorphisms on serum total IgE. The model showed that there was an interaction between the CD14-159 allele T carrier status and H. pylori antibodies on serum total IgE (P=0.004). No other interactions were found. CONCLUSION: Our results further emphasize the role of gene-environment interaction in the regulation of serum total IgE.

Hemodynamic effects of iloprost, a prostacyclin analog.

Iloprost is a chemically stable derivative of carbaprostacyclin. We studied its hemodynamic effects in 10 patients in an intensive care unit. Iloprost was infused intravenously for 3 days for the treatment of advanced obliterative arterial disease of the lower extremities. Clinically significant hemodynamic responses were obtained with an infusion rate of 0.5 ng/kg/min. All subjects tolerated the dose of 4 ng/kg/min, which increased heart rate an average of 11% and cardiac index an average of 26%. This infusion rate decreased mean arterial pressure by 15%, total peripheral resistance by 31%, and pulmonary vascular resistance by 34%. Mean pulmonary arterial pressure, pulmonary capillary wedge pressure, left and right ventricular stroke work indices, and rate pressure product did not change. At higher doses of up to 8 ng/kg/min, responses were augmented only slightly, but side effects such as headache, nausea, and abdominal colics became more prominent. The data show iloprost to be a potent vasodilator that reduces both pre- and afterload and presumably induces a compensatory increase in cardiac output and heart rate, but does not increase the work load or oxygen demand of the heart.

Complications of subclavian vein catheters in patients with high enterocutaneous fistulas.

Complications of subclavian catheters in 17 consecutive patients with high enterocutaneous fistulas were studied. Fifteen patients had drainage surgery and total parenteral nutrition was given to all patients via a subclavian catheter for 27 +/- 20 days and in total 75 catheters were used for 1044 days. One patient needed on average 5.0 +/- 2.2 catheters and one catheter was in place 12.3 +/- 9.7 days. Bacterial cultures were positive in two and candida cultures in one catheter. Three patients died due to sepsis, but only one had a minor complication transient skin infection around the catheter. The frequency of complications decreased when the number of catheters in each patient increased. Minor complications were common.

Suppression of T-cell activation by Lactobacillus rhamnosus GG-degraded bovine casein.

Earlier data indicate that Lactobacillus rhomnosus GG ATCC 53103 (L. GG), a commensal intestinal bacterial strain, promotes the degradation of proteins in the gut in vivo, and bovine casein hydrolysed with L. GG-derived proteases suppresses lymphocyte proliferation in vitro. The present study aimed to evaluate the effect of L. GG-degraded bovine casein on T-cell activation, i.e. IL-2 mRNA expression and protein kinase C (PKC) translocation. To this end, Northern blot analyses for IL-2 mRNA expression and PKC assays with and without L. GG-degraded casein were carried out on T cells isolated from 11 healthy adults. Cell cultures in 8-11 experiments contained 1 mg ml(-1) bovine casein in degraded or undegraded form in the presence of a mitogen, i.e. phorbol 12,13-dibutyrate plus calcium ionophore (PBDu + A23187) or anti-CD3. Also IL-2, IL-4 and IFN-gamma syntheses were determined in 24-h culture supernatants. IL-2 mRNA expression was reduced in experiments with L. GG-degraded casein. In parallel, the IL-2 concentration in PBDu + A23187-stimulated culture supernatants, expressed as geometric means (95% confidence interval), decreased from 15,892 (7174-35,203) pg ml(-1) to 4744 (2095-10,742) pg ml(-1) when containing L. GG-degraded casein. L. GG-degraded casein inhibited PKC translocation, the action resembling that of PKC inhibitor, RO31-8220. These results extend previous data on L. GG-degraded casein, showing in vitro the suppression of T-cell activation.

Metabolic effects of branched chain amino acids in patients with severe pancreatitis.

Twenty-four patients with acute severe pancreatitis were randomised to receive total parenteral nutrition for 7 days with one of two isocaloric (35 kcal/kg/day) and isonitrogenous (0.16 g/kg/day) programmes containing either a low (15.5% w/w (control group)) or a high (57%) content of branched chain amino acids (BCAA (BCAA group)). During treatment, the nitrogen balance was similar in both groups. The concentrations of serum protein, albumin, prealbumin and retinol-binding protein did not differ between the groups. The plasma concentrations of BCAA measured 2 h after discontinuation of amino acid infusions rose in the BCAA group. In urine, only the concentrations of valine increased as compared with those of control patients. Serum glucose levels were higher in the BCAA group than in the control group, although the BCAA group received slightly more insulin than the control group in order to keep the blood glucose concentration below 10 mmol/l. The results suggest that BCAA-enriched solutions may stimulate gluconeogenesis without affecting catabolism.

Evaluating cataract surgery gains by assessing patients' quality of life using the VF-7.

PURPOSE: To describe the development and performance of a questionnaire designed to measure functional impairment caused by cataract. SETTING: Department of Ophthalmology, Helsinki University Central Hospital, Helsinki, Finland. METHODS: The results of a visual-functioning index (VF-14) of 168 patients with first-eye cataract surgery were analyzed. Patients with significant comorbidity were excluded, leaving 142 patients for the final analysis. Snellen visual acuity measurements and complete preoperative and 4 month postoperative clinical status were performed by ophthalmologists. Outcome measures, including the VF-14, patient perception of trouble with vision, patient satisfaction with vision, and the cataract symptom score, were taken by nurses at the preoperative clinical examinations and at the 4 month postoperative visit. The Spearman rank correlation was used to determine which items of the VF-14 best correlated with a change in patient satisfaction. RESULTS: Seven items of the VF-14 that best correlated with patient satisfaction were selected for inclusion in a new 7-item index (the VF-7). Based on the Spearman rank correlation, the items from best to worst were nighttime driving; reading small print; watching television; seeing steps, stairs, or curbs; reading traffic, street, or store signs; cooking; and doing fine handwork. The correlation among changes in the VF-7 score and visual acuity in the operated eye was 0.17, while the correlation among changes in the VF-7 and patient satisfaction caused by cataract surgery was high (r = .56). CONCLUSION: The VF-7 was a strong predictor of change in patient satisfaction caused by cataract surgery.

The intensive care of acute pancreatitis.

The results of medical and surgical treatment of 115 cases of acute pancreatitis treated in the surgical intensive care unit over a period of 8 years are reviewed. The death rate from acute pancreatitis fell during the period of study in the intensive care unit from 42.6% between 1969 and 1973, when drainage was used, to 22.9% between 1974 and 1976 when resection was performed, and in hospital from 8.2% to 5.8% respectively. The results improved as a consequence of adequate treatment of shock, complete intravenous feeding, accurate timing of surgery and the successful choice of operative procedures.

Fecal recovery following oral administration of Lactobacillus strain GG (ATCC 53103) in gelatine capsules to healthy volunteers.

Recovery of the suggested probiotic strain Lactobacillus GG in feces was studied after oral administration. Lactobacillus GG was given to 20 healthy human volunteers for 7 days in gelatine capsules with daily doses of 1.6 x 10(8) cfu and 1.2 x 10(10) cfu. All the volunteers in the higher dose group had detectable numbers of Lactobacillus GG in their feces during the test period. The strain was detected in feces of all the volunteers after 3 days of administration. No effect was observed on the total number of fecal lactobacilli. Fecal detection of the strain may facilitate dose-response studies and provide a useful tool in dietary studies utilizing the strain in foods or food-type products.

Massive resection of the small bowel.

A report is presented on patients (no. = 43. 64 +/- 9 years, 30 men and 13 women) subjected to a massive small bowel resection (69 +/- 25 cm intestine left). The most usual indication was thromboembolism of the arteria mesenterica superioris, but there were also patients who had had intestinal by-pass, occlusion, trauma, tumor and invagination. The preoperative diagnosis was based on peritonitis, increasing abdominal symptoms, paralytic ileus, shock and fever. Fluid and electrolyte treatment, postoperative intensive care, intestinal decompression, parenteral nutrition and antibiotics were also employed. Postoperatively there was a significant decrease in serum protein (SP) (63 +/- 11 vs. 43 +/- 9 g/l) and blood hemoglobin (150 +/- 10 vs. 106 +/- 8 g/l) concentrations (Hb) and hematocrit (CHCT) (0.44 +/- 0.11 vs. 0.31 +/- 0.10). Also the number of patients with subnormal SP and Hb increased from five to nineteen and from fourteen to thirty-two, respectively. The operative mortality (within 30 days) was 60 percent (26/43). Those who survived were younger (59 +/- 8 vs. 67 +/- 9 years) and had higher SP (87 +/- 12 vs. 47 +/- 11 g/l), blood leukocyte count (22 +/- 6 vs. 14 +/- 5 X 10(9] and lower peroperative blood loss (291 +/- 43 vs. 448 +/- 67) than those who died. During the one to 14 year follow-up time nine (21% of all patients and 59% of those who were discharged) were still alive. Thus the patients subjected to a massive small bowel resection are old, have atherosclerotic cardiovascular diseases and preoperatively have peritonitis or severe abdominal complaints and an impaired nutritional state and fluid balance.

The treatment of high enterocutaneous fistula with surgical drainage and total parenteral nutrition.

High enterocutaneous fistulas occurred in 17 malnourished patients after abdominal surgery, performed in most cases for serious primary disease, and were treated with emergency surgical drainage, in 15 cases, early resuturation, in six patients, and total parenteral nutrition (12.6 MJ) in all cases. No elective reconstructions were carried out. The fistulas healed in 27 +/- 20 days, except in three patients, with carcinoma of the stomach or necrosis of the pancreas, who died in sepsis.

Nitrogen-calorie ratio during total parenteral nutrition in 1001 surgical patients treated in intensive care unit.

Nitrogen-calorie (non-nitrogen) ratio during total parenteral nutrition in 1001 successive surgical patients treated in intensive care unit of Tampere Central Hospital over two and a half years was studied. The mortal was three percent in the patients (N = 222) needing only intensive observation, seven per cent in the group (N = 544) needing intensive treatment and 54 per cent in the patients needing intensive therapy (N = 287). Complete parenteral nutrition was only one aspect of the total intensive treatment and it was fulfilled in harmony with the other forms of treatment to safe the life of these critically ill patients. Thus e.g. the clinical status, blood circulation, respiratory function, renal function, blood gas, blood glucose concentration, diuresis and excretion of urea were followed. Complete parenteral nutrition by 15 per cent fructose-glucose solution, 20 per cent fat emulsion (Intralipid), and/or aminoacid solution (Levamin forte, 1000 ml = 11 grams amino-nitrogen and 400 kcal) was given to 87.6 per cent of the patients for 3717 days of treatment. The results showed that nitrogen-calorie ratio during total parenteral nutrition in 1001 surgical patients treated in intensive care unit was 1:125, indicating a low amount of energy given for each gram of administered nitrogen. The nitrogen-calorie ratio for the patients who needed only intensive observation, intensive treatment or intensive therapy were: 1:112, 1:130 or 1:121, respectively.