Diagnostic tests and treatment procedures performed prior to cardiovascular death in individuals with severe mental illness.

OBJECTIVE: To examine whether severe mental illnesses (i.e., schizophrenia or bipolar disorder) affected diagnostic testing and treatment for cardiovascular diseases in primary and specialized health care. METHODS: We performed a nationwide study of 72 385 individuals who died from cardiovascular disease, of whom 1487 had been diagnosed with severe mental illnesses. Log-binomial regression analysis was applied to study the impact of severe mental illnesses on the uptake of diagnostic tests (e.g., 24-h blood pressure, glucose/HbA1c measurements, electrocardiography, echocardiography, coronary angiography, and ultrasound of peripheral vessels) and invasive cardiovascular treatments (i.e., revascularization, arrhythmia treatment, and vascular surgery). RESULTS: Patients with and without severe mental illnesses had similar prevalences of cardiovascular diagnostic tests performed in primary care, but patients with schizophrenia had lower prevalences of specialized cardiovascular examinations (prevalence ratio (PR) 0.78; 95% CI 0.73-0.85). Subjects with severe mental illnesses had lower prevalences of invasive cardiovascular treatments (schizophrenia, PR 0.58; 95% CI 0.49-0.70, bipolar disorder, PR 0.78; 95% CI 0.66-0.92). The prevalence of invasive cardiovascular treatments was similar in patients with and without severe mental illnesses when cardiovascular disease was diagnosed before death. CONCLUSION: Better access to specialized cardiovascular examinations is important to ensure equal cardiovascular treatments among individuals with severe mental illnesses.

Undiagnosed cardiovascular disease prior to cardiovascular death in individuals with severe mental illness.

OBJECTIVE: To examine whether individuals with schizophrenia (SCZ) or bipolar disorder (BD) had equal likelihood of not being diagnosed with cardiovascular disease (CVD) prior to cardiovascular death, compared to individuals without SCZ or BD. METHODS: Multivariate logistic regression analysis including nationwide data of 72 451 cardiovascular deaths in the years 2011-2016. Of these, 814 had a SCZ diagnosis and 673 a BD diagnosis in primary or specialist health care. RESULTS: Individuals with SCZ were 66% more likely (OR: 1.66; 95% CI: 1.39-1.98), women with BD were 38% more likely (adjusted OR: 1.38; 95% CI: 1.04-1.82), and men with BD were equally likely (OR: 0.88, 95% CI: 0.63-1.24) not to be diagnosed with CVD prior to cardiovascular death, compared to individuals without SMI. Almost all (98%) individuals with SMI and undiagnosed CVD had visited primary or specialized somatic health care prior to death, compared to 88% among the other individuals who died of CVD. CONCLUSION: Individuals with SCZ and women with BD are more likely to die due to undiagnosed CVD, despite increased risk of CVD and many contacts with primary and specialized somatic care. Strengthened efforts to prevent, recognize, and treat CVD in individuals with SMI from young age are needed.

Expression of DSG1 and DSC1 are prognostic markers in anal carcinoma patients.

BACKGROUND: Our purpose was to investigate if dysregulation of cell adhesion molecules could be linked to prognosis in squamous cell carcinomas (SCCs) of the anal region. METHODS: Protein expression of desmoglein-1 (DSG1), desmocollin-1 (DSC1) and E-cadherin was studied by immunohistochemistry in a cohort of 53 anal carcinoma patients treated by radiation alone or combined with 5-fluorouracil and mitomycin C. RESULTS: Univariate analyses identified, among others, negative membranous DSG1 staining (P=0.009), negative cytoplasmic DSC1 staining (P=0.012) and negative DSG1 (membranous)+negative DSC1 (cytoplasmic) staining (P=0.004) to be associated with improved cancer-specific survival (CSS). On multivariate analyses positive DSG1 (membranous)+DSC1 (cytoplasmic) staining (HR 6.95, P=0.044), large tumour size and lymph node metastases (HR 6.44, P=0.004) and radiation without chemotherapy (HR 6.73 P=0.004) were associated with worse CSS. On univariate analysis, improved disease-free survival was associated with negative membranous staining of DSG1 (P=0.047), and negative DSG1 (membranous)+negative DSC1 (cytoplasmic) staining (P=0.025), among others. CONCLUSION: Membrane negativity for DSG1 and cytoplasmic negativity for DSC1 are favourable markers for CSS in SCCs of the anal region.

MicroRNA-15b is induced with E2F-controlled genes in HPV-related cancer.

BACKGROUND: MicroRNAs (miRNAs) are important regulators of cellular processes and are found to be deregulated in many cancers. We here analysed the miRNA expression in anal carcinomas. In a previous study, we found that our anal carcinoma tumours were divided into two groups based on the expression of E2F-regulated genes. Therefore, we searched for miRNAs that could reproduce this grouping. METHODS: A global screen of the miRNA population was performed using real-time quantitative PCR (RT-qPCR) array methods and differentially expressed miRNAs were identified. Real-time-qPCR was used to verify the expression levels of selected miRNAs and genes in a larger collection of biopsies. A siRNA-mediated knockdown of human papilloma virus (HPV)16 E7 in a cervical cell line was performed to assess the effect of E7 on miR-15b. RESULTS: The grouping of tumours into two groups based on the expression of E2F-controlled genes was confirmed in a larger collection of anal carcinoma tumours. The expression of miR-15b was shown to be highly correlated with that of five selected E2F-induced genes (CCNA2, CCNB1, CCNB2, MSH6 and MCM7). A knockdown of HPV16 E7 resulted in decreased levels of miR-15b in Ca Ski cells. CONCLUSION: MiR-15b expression correlates with E2F-regulated genes in anal carcinoma and appears to be part of the E2F-regulatory network.

Hip fractures in a city in Northern Norway over 15 years: time trends, seasonal variation and mortality : the Harstad Injury Prevention Study.

UNLABELLED: In this open population-based study from Northern Norway, there was no increase in hip fracture incidence in women and men from 1994 to 2008. Age-adjusted hip fracture rates was lower compared to reported rates from the Norwegian capital Oslo, indicating regional differences within the country. INTRODUCTION: The aim of the present population-based study was to describe age- and sex-specific incidence of hip fractures in a Northern Norwegian city, compare rates with the Norwegian capital Oslo, describe time trends in hip fracture incidence, place of injury, seasonal variation and compare mortality after hip fracture between women and men. METHODS: Data on hip fractures from 1994 to 2008 in women and men aged 50 years and above were obtained from the Harstad Injury Registry. RESULTS: There were altogether 603 hip fractures in Harstad between 1994 and 2008. The annual incidenc rose exponentially from 5.8 to 349.2 per 10,000 in men, and from 8.7 to 582.2 per 10,000 in women from the age group 50-54 to 90+ years. The age-adjusted incidence rates were 101.0 and 37.4 in women and men, respectively, compared to 118.0 in women (p = 0.005) and 44.0 in men (p = 0.09) in Oslo. The age-adjusted incidence rates did not increase between 1994-1996 and 2006-2008. The majority of hip fractures occurred indoors and seasonal variation was significant in fractures occurring outdoors only. After adjusting for age at hip fracture, mortality after fracture was higher in men than in women 3, 6 and 12 months (p ≤ 0.002) after fracture. CONCLUSIONS: There are regional differences in hip fracture incidence that cannot be explained by a north-south gradient in Norway. Preventive strategies must be targeted to indoor areas throughout the year and to outdoor areas in winter.

Locally recurrent rectal cancer in Norway.

BACKGROUND: The purpose of this study was to describe management and outcome in patients with locally recurrent rectal cancer based on data from the Norwegian Colorectal Cancer Registry. METHODS: This was a prospective national cohort study of 577 patients with local recurrence after major resection (R0/R1) for rectal cancer between November 1993 and December 2001 (initial cohort of 4504 patients). RESULTS: Of the 577 patients, 185 (32.1 per cent) had curative resections (R0/R1), 203 (35.2 per cent) had palliative radiotherapy with or without palliative surgery and chemotherapy, and 189 (32.8 per cent) received no treatment at all or only palliative surgery or chemotherapy. The overall 5-year survival rate was 14.9 per cent. Ninety-seven patients had an R0 resection, and 88 had an R1 resection, with 5-year overall survival of 55 and 20 per cent respectively. This outcome reflected surgical treatment in 33 different hospitals. Some 274 patients (47.5 per cent) had metastases. The 5-year survival rate after R0 resection was 62 per cent in patients without metastases. CONCLUSION: Obtaining an R0 resection is the most important prognostic factor in treating recurrent rectal cancer.

A randomized phase III multicenter trial comparing irinotecan in combination with the Nordic bolus 5-FU and folinic acid schedule or the bolus/infused de Gramont schedule (Lv5FU2) in patients with metastatic colorectal cancer.

BACKGROUND: To compare irinotecan with the Nordic 5-fluorouracil (5-FU) and folinic acid (FA) bolus schedule [irinotecan 180 mg/m(2) on day 1, 5-FU 500 mg/m(2) and FA 60 mg/m(2) on day 1 and 2 (FLIRI)] or the Lv5FU2 schedule [irinotecan 180 mg/m(2) on day 1, FA 200 mg/m(2), 5-FU bolus 400 mg/m(2) and infused 5-FU 600 mg/m(2) on day 1 and 2 (Lv5FU2-IRI)] due to uncertainties about how to administrate 5-FU with irinotecan. PATIENTS AND METHODS: Patients (n = 567) with metastatic colorectal cancer were randomly assigned to receive FLIRI or Lv5FU2-IRI. Primary end point was progression-free survival (PFS). RESULTS: Patient characteristics were well balanced. PFS did not differ between groups (median 9 months, P = 0.22). Overall survival (OS) was also similar (median 19 months, P = 0.9). Fewer objective responses were seen in the FLIRI group (35% versus 49%, P = 0.001) but the metastatic resection rate did not differ (4% versus 6%, P = 0.3). Grade 3/4 neutropenia (11% versus 5%, P = 0.01) and grade 2 alopecia (18% versus 9%, P = 0.002) were more common in the FLIRI group. The 60-day mortality was 2.4% versus 2.1%. CONCLUSIONS: Irinotecan with the bolus Nordic schedule (FLIRI) is a convenient treatment with PFS and OS comparable to irinotecan with the Lv5FU2 schedule. Neutropenia and alopecia are more prevalent, but both regimens are equally well tolerated.

Chronomodulated capecitabine in combination with short-time oxaliplatin: a Nordic phase II study of second-line therapy in patients with metastatic colorectal cancer after failure to irinotecan and 5-flourouracil.

BACKGROUND: Oxaliplatin in combination with capecitabine prolongs survival in patients with metastatic colorectal cancer (mCRC). Chronomodulation might reduce toxicity and improve efficacy. PATIENTS AND METHODS: A phase II study examining chronomodulated XELOX(30) (XELOX(30chron)): oxaliplatin: 130 mg/m(2) on day 1, as a 30-min infusion between 1 and 3 p.m. Capecitabine: total daily dose of 2000 mg/m(2), 20% of the dose between 7 and 9 a.m. and 80% of the dose between 6 and 8 p.m. in patients with mCRC resistant to irinotecan. Seventy-one patients were enrolled. Response rate was 18%; median progression-free survival 5.1 months and median overall survival (OS) 10.2 months. Platelet count and performance status were significantly correlated to OS in multivariate analyses. Neurotoxicity grade 2 and 3 was seen in 25% and 2% of patients, respectively, other grade 3 toxic effects were as follows: nausea 6%, vomiting 3%, diarrhoea 12% (3% experienced grade 4) and palmoplantart erytem 9%. CONCLUSION: XELOX(30chron) is a convenient second-line regimen with efficacy and safety profile similar to other oxaliplatin schedules. To further investigate chronomodulated XELOX, we have started a Nordic randomised phase II study comparing XELOX(30) and XELOX(30chron) as first-line therapy in patients with mCRC.

Treatment of acute myocardial infarction in the sub-arctic region of Norway. Do we offer an equal quality of care?

Patients, relatives, healthcare workers and administrators are concerned about the quality of care offered. We aimed to explore the treatment of acute myocatrdial infarction (AMI) in Northern Norway, compare it with the national figures, and document whether there is an equal quality of care or not. The retrospective study included data on patients' treatment for AMI. The following sources were employed. The Norwegian Patient Registry, National Quality of Care Database, Norwegian Myocardial Infarction Registry and data from the National Air Ambulance Services of Norway. The period 2012-2014/15 was studied and the variables were: incidence of AMI, gender and age adjusted rates of AMI and revascularization (PCI, CABG) based on patient's place of living (according to hospital catchment area) and 30-day survival rate. The annual incidence of AMI was 9% higher in the northern region. Significant incidence variations (2.7-5.9 AMI/1000 inhabitants) between the hospitals' catchment areas were revealed. The 30-day survival rate varied between 85.1-92.1% between hospitals. The variation in revascularization/AMI rate was 0.72-1.54. Air amublance services' availability varied through the day. In conclusion, significant variations in the AMI rate and an unequal service within the region was revealed.

Thromboxane production in the blood of women increases after menopause whereas tumor necrosis factor is reduced in women compared with men.

Previously we have shown that incubation of heparinized blood with a low dose of lipopolysaccharides (5 ng/ml) resulted in a 60% higher generation of TxB2 in the blood of young men as compared with that of young women. In the present study, we investigated a group consisting of 38 healthy men and 38 healthy postmenopausal women aged 50-73 years with no drug use and no known chronic disease. In contrast to our earlier observation that young men produce more TxB2 than young women, no significant difference was observed between the men and women when all the participants above 50 years of age were included (5.7 +/- 0.6 ng/l for men versus 5.2 +/- 0.7 ng/l for women). However, a strong correlation was found with simple regression analysis when increasing TxB2 generation was compared with years after menopause (P < 0.0001). No such correlation was observed for increasing age of men and their TxB2 production. The LPS stimulation system of whole blood was also used to evaluate the production of tumor necrosis factor (TNF-alpha) in older people. Men were found to generate 60% more TNF-alpha than women, but no correlation was found between increasing age of women and TNF-alpha production as observed with TxB2. Risk factors such as SDS-cholesterol, fibrinogen and factor VII were the same in men and women, whereas total cholesterol was higher in women than in men (P < 0.05). Since TxA2 is known to be a mediator of atherosclerotic-induced lesions and TNF-alpha is a well-established indicator of inflammatory reactions, we propose that the reduced production of TxB2 and TNF-alpha in women in our model system may partially explain the lower incidence of atherosclerosis in women as compared with men, and the phenomenon of increased incidence of this disease after menopause.

Growth hormone pre-treatment combined with exogenous glutamine induced a postoperative shift from glucose to glutamine consumption in the gastrointestinal tract.

The aim of this study was to assess whether the protein sparing effects associated with administration of growth hormone (GH) and glutamine in the early post traumatic period deprive the gastrointestinal tract of substrates. Sixteen piglets were randomized to receive GH treatment (n = 8) for 3 days prior to surgery whilst a control group (n = 8) received no growth hormone. Organ fluxes of glucose, lactate, pyruvate, alanine and glutamine were measured at 1 and 5 h after surgery. An infusion of glutamine (36 microg/kg/min) was started after the first measurement in both groups. In the GH group (5 h after surgery), hindleg release of glutamine and alanine was found to be lower than in the control group, whilst intestinal glutamine uptake was higher and that of alanine was lower. Hepatic alanine uptake was reduced whilst hepatic glutamine exchange switched from uptake to release. Intestinal glucose consumption was lower in the GH group (P < 0.05). It is concluded that GH pre-treatment in combination with exogenous glutamine administration induced a shift in gastrointestinal fuel selection which was associated with reduced glucose consumption and increased glutamine consumption. The effect of GH in inducing hepatic release of glutamine compensated for its effect on muscle which results in reduced peripheral glutamine release.

Effects of insulin-like growth factor 1 on neutrophil and monocyte functions in normal and septic states.

BACKGROUND: Insulin-like growth factor 1 (IGF-1) mediates anabolic actions in catabolic states and also influences the immune system. Endogenous IGF-1 production is suppressed in sepsis; replacement therapy is therefore a natural approach to obtain the protein anabolic and potentially immune-stimulating effects of IGF-1. METHODS: Twenty-two piglets were randomized to three groups: an IGF-1 group (n = 8) receiving a continuous infusion of 1.3 mg/h of IGF-1, a nontreated septic control group (n = 8), and a nonseptic control group (n = 6) receiving saline. Phagocytosis and respiratory burst in porcine neutrophils were evaluated by flow cytometry (FCM); tumor necrosis factor (TNF) levels were measured in serum during the septic period. In addition, human neutrophils and monocytes were primed in vitro with IGF-1 and subsequently were stimulated with phorbol myristate acetate (PMA) or Escherichia coli; phagocytosis and respiratory burst were evaluated by FCM. RESULTS: Under nonseptic conditions, pretreatment with IGF-1 suppressed the ability of neutrophils to ingest bacteria (ie, the level of phagocytosis) 43.4% +/- 2.7% (IGF-1-treated) vs 55.8% +/- 3.4% (nontreated septic controls) and 57.3% +/- 3.34% (nonseptic controls) (p = .01). When challenged by live E. coli infusion, phagocytosis increased in the IGF-1 group to the levels of the nontreated group. The respiratory burst showed a convincing priming effect of IGF-1. After 4 hours of sepsis, the mean fluorescence intensity was 63.1 +/- 6.9 in the IGF-1 group and 40.7 +/- 3.0 in nontreated septic controls. The serum levels of TNF-alpha in the nontreated septic control group were twice those in the IGF-1-treated group, ie, 65.7 +/- 13.1 pg/mL in the nontreated septic controls and 31.5 +/- 7.5 pg/mL in the IGF-1 group (p = .03). In vitro priming of human neutrophils and monocytes with IGF-1 and subsequent stimulation with PMA or E. coli demonstrated that IGF-1 enhanced both phagocytosis and respiratory burst. CONCLUSIONS: IGF-1 serves as a priming agent for biologic functions of leukocytes.

Ralitrexed (Tomudex) or Nordic-FLv regimen in metastatic colorectal cancer: a randomized phase II study focusing on quality of life, patients' preferences and health economics.

Raltitrexed (Tomudex) is proven effective in metastatic colorectal cancer. Between 1998-2000, 25 patients were included in a randomized phase II study comparing raltitrexed (13 patients) and the Nordic FLv regimen (12 patients). 23 patients were evaluable for response. The overall response rate was 2/12 (1 CR, 1 PR) in the raltitrexed arm and 1/11 (1 CR) in the Nordic FLv arm, respectively. There was no difference in overall survival (raltitrexed--14.7 months, Nordic FLv--15.4 months). 23 patients were evaluable for Quality of Life (QoL) analysis. 23/25 and 17/21 questionnaires (EORTC QLQ C-30) were returned at baseline and first evaluation. Raltitrexed tended to be the most toxic regimen, when looking at nausea and vomiting, appetite loss, diarrhea and global QoL. However, most patients (65%) recommended the raltitrexed treatment schedule. The total treatment cost was equal in both arms (about 6,800 EURO/patient) and the hospital/hospital hotel stay costs accounted for more than half of it.

Gene expression reveals two distinct groups of anal carcinomas with clinical implications.

Human papillomavirus (HPV) is a major aetiological agent in anal carcinomas. We here present a study of global gene expression using microarray hybridisation in a collection of anal carcinoma biopsies. Quantitative PCR was used to verify expression of selected genes. All biopsies contained integrated DNA of human papillomavirus subtype 16 (HPV16) and expressed HPV16 E7 mRNA. No other subspecies of HPV were detected in these 13 biopsies as assessed by PCR amplification and DNA sequencing. Unsupervised cluster analysis, based on global mRNA expression, divided the tumour biopsies into two distinct groups. Cluster analysis based on a number of high-risk HPV and/or E2F-regulated genes reproduced this biopsy grouping, suggesting that integrated HPV16 substantially influenced global gene expression in approximately half the biopsies studied. The levels of HPV16 E7 mRNA were significantly different between the two groups, but with considerable overlap. Thus, influence on global gene expression could not be absolutely ascribed to the expression level of HPV16. To investigate whether this distinction in gene expression had prognostic impact, we studied protein expression in an independent cohort of 55 anal carcinomas not included in the microarray study of two differentially expressed candidate genes, minichromosome maintenance complex component 7 (MCM7) and cyclin-dependent kinase inhibitor 2A (CDKN2A or p16). HPV status was assessed by in situ hybridisation. There was a significant association between in situ staining for HPV E7 mRNA and immunostaining for CDKN2A (p16) and MCM7 protein. CDKN2A (p16) mRNA was found significantly differentially expressed between the two tumour groups. However, cluster analysis on genes directly regulated by CDKN2A (p16) could not reproduce this split of biopsies into two groups, suggesting that the transcriptional regulatory activity of CDKN2A in these biopsies is inhibited. Furthermore, protein expression of CDKN2A (p16) could not be associated with survival. MCM7 is directly regulated by E2F and induced by HPV, and its mRNA was found differentially expressed between the two tumour groups. High level of MCM7 protein was found to be associated with both improved relapse-free survival (RFS, P=0.02) and cancer-specific survival (CSS, P=0.03) in anal cancer patients treated with radiation with or without additional chemotherapy.

Growth hormone impaired compensation of hemorrhagic shock after trauma and sepsis in swine.

OBJECTIVE: To study hemodynamic effects of growth hormone (GH) and its main mediator, insulin-like growth factor-1, in a model of critical illness. DESIGN: Randomized experiment in traumatized and septic piglets. MATERIALS AND METHODS: Hemodynamics and blood gases before and sustained volume loss during a controlled, fatal hemorrhage were recorded in a GH treated group (n = 8), an insulin-like growth factor-1 treated group (n = 8), a control group with trauma and sepsis (n = 8), and a control group with trauma only (n = 6). MEASUREMENTS AND MAIN RESULTS: Sustained volume loss before cardiac arrest was lower in the GH group. The GH group was characterized by metabolic acidosis. During the hemorrhage, visceral blood flow (portal and renal) as a fraction of cardiac output (fractional flow) was lower and peripheral fractional flow higher in the GH group. Fractional renal artery flow was higher in the insulin-like growth factor-1 group (p < 0.05 for the comparisons stated). CONCLUSION: GH promoted metabolic acidosis in traumatized sepsis and impaired compensation of a subsequent hemorrhage.

Both growth hormone and exogenous glutamine increase gastrointestinal glutamine uptake in trauma.

OBJECTIVE: The authors studied the effect of exogenous glutamine (GLN), with and without growth hormone (GH), pretreatment, on gastrointestinal, hepatic, femoral, and renal GLN fluxes. SUMMARY BACKGROUND DATA: Growth hormone treatment increases gastrointestinal uptake of GLN despite a reduced skeletal muscle and whole body release. METHODS: Piglets were randomized to a GH + GLN group (n = 8), a GLN group (n = 8), a GH group (n = 8), and a control group (CON; n = 8). Genotropin (Pharmacia, Stockholm, Sweden; 24 international units; correspondingly saline in the GLN and the CON group) was given daily 3 days before and at the onset of trauma (surgery). Organ fluxes and whole body release of GLN were determined 1 and 5 hours after surgery. An infusion of GLN 36 micrograms/kg per minute was started after the first measurement in the GH + GLN and the GLN groups. RESULTS: Both GH treatment and exogenous GLN increased gastrointestinal GLN uptake (p = 0.001 and p = 0.02, respectively). Growth hormone treatment reduced hepatic GLN uptake (p = 0.001). Hepatic GLN uptake was lower in the GH + GLN group versus the GH group (p = 0.02), but not in the GLN group versus the CON group (p = 0.98). Growth hormone treatment reduced femoral and whole-body GLN release (p = 0.0001 and p = 0.02, respectively). Renal GLN uptake was higher in the two GH-treated groups (p = 0.003). CONCLUSION: Both exogenous GLN and GH increased gastrointestinal GLN uptake, and the combination was additive. In contrast to exogenous GLN, GH reduced hepatic uptake and consequently facilitated the increased gastrointestinal GLN uptake that occurred despite reduced femoral and whole-body release.

Growth hormone increases and IGF-1 reduces the response to Escherichia coli infusion in injured pigs.

OBJECTIVE: To investigate if growth hormone (GH) or its main mediator insulin-like growth factor-1 (IGF-1) alters the response to infusion of live Escherichia coli in injured pigs. DESIGN: Controlled experiment. SETTING: University laboratory, Norway. SUBJECTS: 30 piglets. INTERVENTIONS: The response to infusion of Escherichia coli was compared after a bolus of GH 16 IU (n = 8) or a continuous infusion of IGF-1 1.3 mg/hour (n = 8) in injured piglets. A group with trauma (surgery) and Escherichia coli infusion (n = 8) and a group with trauma only (n = 6) served as controls. MAIN OUTCOME MEASURES: Systemic and regional haemodynamics, oxygen consumption, and acid-base regulation; and circulating concentrations of catecholamines, free fatty acids (FFA), glucose, and lactate Results: After infusion of Escherichia coli, cardiac output was lower and heart rate was higher in the GH than in the IGF-1-treated group. Aortic pH was lower in the GH group compared with the septic controls, whereas aortic pH was higher in the IGF-1 group compared with the septic controls. Portal vein pH was lower in the GH group than in the other three groups. Free fatty acids and lactate concentrations were higher in the GH group than in the other three groups. Glucose concentrations were lower in the IGF-1 group than in the other three groups. Renal artery flow was higher in the IGF-1 than in the GH group and the septic controls. Circulating concentrations of dopamine was higher in the IGF-1 group than in the other three groups, whereas that of noradrenaline was higher in the GH group than in the IGF-1 group. (For all differences stated, p < 0.05). CONCLUSIONS: Acute treatment with GH increased the circulatory and metabolic response to Escherichia coli infusion, in contrast to treatment with IGF-1, which reduced the response

Repeated plasma therapy induces fatal shock in experimental septicemia.

Plasma therapy in severe septicemia, either as part of plasma exchange or alone, was evaluated in a model of lethal septic shock induced with live Escherichia coli in pigs. The following groups were studied: group I, septic animals treated with repeated plasma exchanges, n = 8; group II, nontreated septic controls, n = 8; group III, septic animals treated with repeated plasma infusions, n = 14; and group IV, nonseptic animals treated with repeated plasma infusions, n = 7. In the septic animals treated with plasma (groups I and III), a rapid fatal response was observed between 2 and 5 min after the start of plasma therapy, while the septic controls (group II) showed a progressively longer lasting septic shock. The nonseptic animals (group IV) were unaffected by the plasma infusions. Plasma levels of endotoxin above 2 ng/ml were associated with rapid death during plasma therapy. Ionized Ca2+ fell abruptly in this situation. This study indicates that commonly used plasma therapies (exchanges or transfusions) in septic animals may have acute deleterious effects. These effects may be explained by depletion of ionized calcium.

Fatal myocardial depression and circulatory collapse associated with complement activation induced by plasma infusion in severe porcine sepsis.

We have previously reported that fresh frozen plasma (FFP) may induce a rapid irreversible shock when repeatedly infused in pigs challenged with Gram-negative sepsis. The aims of the present study were to elucidate the cardiovascular nature of the shock and determine the aetiologic role of tumour necrosis factor (TNF), complement activation and halothane anaesthesia. Three groups of anaesthetized piglets were inoculated with a lethal dose of live E. coli bacteria. Groups I (n = 8) and III (n = 8) were anaesthetized with halothane and group II (n = 8) with ketamine. Animals in groups I and II received repeated infusions of FFP, whereas animals in group III received repeated infusions of 7% albumin. Six animals in group I and four animals in group II died during the first plasma infusion. Survival time was significantly longer in group II (P = 0.04) compared to group I. No animals in group III died during the albumin infusions, and no adverse effects were observed during the infusions. In group I the plasma induced shock was characterized by abruptly falling mean arterial pressure, cardiac index, systemic vascular resistance index and left ventricular contractility. Concomitant increases were recorded in left ventricular filling pressure and central venous pressure. Group II demonstrated a similar, but delayed response. Plasma infusion was associated with a significant increase in terminal complement complex (TCC) (P < 0.03 in group I, P < 0.05 in group II) and depletion of serum ionized calcium. We conclude that FFP may induce fatal myocardial depression and circulatory collapse in severe sepsis. Complement activation may be of aetiologic importance.

Treatment with growth hormone and insulin-like growth factor-1 in septicemia: effects on carbohydrate metabolism.

Growth hormone (GH) and insulin-like growth factor-1 (IGF-1) may be beneficial against the protein catabolism seen in injury and septicemia. Further understanding of their effects on carbohydrate metabolism is needed. In a septic porcine model receiving total parenteral nutrition, pretreatment with GH or IGF-1 (or no treatment in controls) was followed by an infusion of live Escherichia coli bacteria. Endogenous glucose production, carbohydrate oxidation, glucose and lactate fluxes over the liver, gastrointestinal organs, kidney, and hindleg were determined. Endogenous glucose production increased during septicemia in the GH group. The metabolic acidosis induced by septicemia was augmented by GH, but attenuated by IGF-1. The alanine and lactate levels were significantly higher in the GH- than in the IGF-1 treated animals during septicemia. IGF-1 pretreatment appeared to induce favorable effects while GH pretreatment might produce unfavorable effects on carbohydrate metabolism in septic piglets.