Distinguishing independent and shared effects of material/structural conditions and psychosocial resources on educational inequalities in self-rated health: results from structural equation modelling.

OBJECTIVES: The aim of this study was to distinguish independent and shared effects of material/structural factors and psychosocial resources in explaining educational inequalities in self-rated health (SRH) by using structural equation modelling. STUDY DESIGN: Cross-sectional survey. METHODS: Data were derived from a questionnaire sent to a random sample of the population in five counties in Sweden in 2008. The study population (aged 25-75 years) included 15,099 men and 17,883 women. Exploratory structural equation modelling was used to analyse the pathways from educational level to SRH. RESULTS: The pathway including both material/structural factors (e.g. financial buffer and unemployment) and psychosocial resources (e.g. sense of coherence and social participation) explained about 40% of educational differences in SRH for both men and women. The pathways including only the independent effects of psychosocial resources (14% in men and 20% in women) or material/structural factors (9% and 18%, respectively) explained substantial but smaller proportions of the differences. CONCLUSIONS: The major pathway explaining educational inequalities in SRH included both material/structural factors and psychosocial resources. Therefore, to reduce educational inequalities in SRH, interventions need to address both material/structural conditions and psychosocial resources across educational groups.

Community-acquired pneumonia in primary care: clinical assessment and the usability of chest radiography.

OBJECTIVES: To investigate the diagnostic value of different clinical and laboratory findings in pneumonia and to explore the association between the doctor's degree of suspicion and chest X-ray (CXR) result and to evaluate whether or not CXR should be used routinely in primary care, when available. DESIGN: A three-year prospective study was conducted between September 2011 and December 2014. SETTING: Two primary care settings in Linköping, Sweden. SUBJECTS: A total of 103 adult patients with suspected pneumonia in primary care. MAIN OUTCOME MEASURES: The physicians recorded results of a standardized medical physical examination, including laboratory results, and rated their suspicion into three degrees. The outcome of the diagnostic variables and the degree of suspicion was compared with the result of CXR. RESULTS: Radiographic pneumonia was reported in 45% of patients. When the physicians were sure of the diagnosis radiographic pneumonia was found in 88% of cases (p < 0.001), when quite sure the frequency of positive CXR was 45%, and when not sure 28%. Elevated levels of C-reactive protein (CRP) ≥ 50mg/L were associated with the presence of radiographic pneumonia when the diagnosis was suspected (p < 0.001). CONCLUSION: This study indicates that CXR can be useful if the physician is not sure of the diagnosis, but when sure one can rely on one's judgement without ordering CXR. KEY POINTS: There are different guidelines but no consensus on how to manage community-acquired pneumonia in primary care. When the physician is sure of the diagnosis the judgement is reliable without chest X-ray and antibiotics can be safely prescribed. Chest X-ray can be useful in the assessment of pneumonia in primary care, when the physician is not sure of the diagnosis.

Provitamin A carotenoids are independently associated with matrix metalloproteinase-9 in plasma samples from a general population.

BACKGROUND AND AIM: Carotenoids in plasma are inversely associated with cardiovascular risk. Low levels can be explained by low dietary intake but also by a number of other factors including inflammatory activity. Given that matrix metalloproteinase (MMP)-9 has an important role in inflammation and cardiovascular disease, we hypothesized that circulating MMP-9 levels would be inversely related to total or single carotenoids in a general population cohort. METHODS: A well-characterized population-based cohort of 285 Swedish men and women (45-69 years) was used for the present study. The intake of carotenoid-rich fruits and vegetables was estimated from a food frequency questionnaire. Levels of MMP-9, C-reactive protein (CRP), interleukin (IL)-6 and six major carotenoids [ß-cryptoxanthine, α-carotene, ß-carotene, lutein (+zeaxanthin) and lycopene] were determined in plasma. RESULTS: Lower plasma levels of total and single carotenoids were associated with lower dietary intake of carotenoids, older age, male sex, lower physical activity, higher alcohol consumption, higher body mass index (BMI), higher systolic and diastolic blood pressures, lower levels of total cholesterol and HDL cholesterol and higher levels of CRP, IL-6 and MMP-9. After multivariate adjustments, plasma levels of total carotenoids and provitamin A carotenoids (ß-cryptoxanthine, α-carotene and ß-carotene) remained independently associated with sex, dietary intake of carotenoids, BMI, HDL cholesterol and MMP-9, whilst associations with CRP and IL-6 were not maintained. Neither dietary intake of carotenoid-rich fruits and vegetables, nor vitamin supplement use was associated with MMP-9, CRP or IL-6 levels. CONCLUSION: Plasma carotenoids were associated with a variety of factors including age, sex, dietary intake and metabolic variables. A new finding was the independent relationship in plasma between low provitamin A carotenoids and high MMP-9, suggesting a link between these carotenoids, matrix turnover and arterial remodelling.

Hepatocyte growth factor in patients with coronary artery disease and its relation to periodontal condition.

Hepatocyte growth factor (HGF) is an angiogenic, cardioprotective factor important for tissue and vascular repair. High levels of HGF are associated with chronic inflammatory diseases, such as coronary artery disease (CAD) and periodontitis, and are suggested as a marker of the ongoing atherosclerotic event in patients with CAD. Periodontal disease is more prevalent among patients with CAD than among healthy people. Recent studies indicate a reduced biological activity of HGF in different chronic inflammatory conditions. Biologically active HGF has high affinity to heparan sulfate proteoglycan (HSPG) on cell-membrane and extracellular matrix. The aim of the study was to investigate the serum concentration and the biological activity of HGF with ELISA and surface plasmon resonance (SPR), respectively, before and at various time points after percutaneous coronary intervention (PCI) in patients with CAD, and to examine the relationship with periodontal condition. The periodontal status of the CAD patients was examined, and the presence of P. gingivalis in periodontal pockets was analyzed with PCR. The HGF concentration was significantly higher, at all time-points, in patients with CAD compared to the age-matched controls (P< 0.001), but was independent of periodontal status. The HGF concentration and the affinity to HSPG adversely fluctuated over time, and the biological activity increased one month after intervention in patients without periodontitis. We conclude that elevated concentration of HGF but with reduced biological activity might indicate a chronic inflammatory profile in patients with CAD and periodontitis.

Correlation between rises in Chlamydia pneumoniae-specific antibodies, platelet activation and lipid peroxidation after percutaneous coronary intervention.

We recently showed that Chlamydia pneumoniae activates platelets in vitro, with an associated oxidation of low-density lipoproteins. The aim of this study was to investigate whether C. pneumoniae is released during percutaneous coronary intervention (PCI) and, thereby, causes platelet activation and lipid peroxidation. Seventy-three patients undergoing coronary angiography and following PCI or coronary artery bypass graft (CABG) and 57 controls were included in the study. C. pneumoniae antibodies, serotonin and lipid peroxidation were measured before and 24 h, 1 month and 6 months after angiography. The results show that serum C. pneumoniae IgA concentrations were significantly higher in patients than in the controls. Furthermore, in 38% of the C. pneumoniae IgG positive patients, the C. pneumoniae IgG concentration increased 1 month after PCI. The levels of C. pneumoniae IgG antibodies 1 month after PCI correlated with plasma-lipid peroxidation (r = 0.91, P < 0.0001) and platelet-derived serotonin (r = 0.62, P = 0.02). There was no elevation in the total serum IgG 1 month after PCI. In conclusion, the present results suggest that PCI treatment of coronary stenosis releases C. pneumoniae from the atherosclerotic lesions, which leads to platelet activation and lipid peroxidation.

Cavoportal hemitransposition in liver transplantation.

Over the last decade a large number of patients with portal vein thrombosis have undergone successful liver transplantation. In most of these patients, simple modifications in vascular reconstruction techniques are adequate. However, anastomosis of the donor portal vein may not be possible in the presence of extensive portal and superior mesenteric venous thrombosis and in the absence of any other large tributary of the portal venous system. Cavoportal hemitransposition has been described as a salvage technique under these circumstances. We report a 43-year-old patient who underwent such a procedure and remains well 1 year later. We review the literature and discuss the implications of cavoportal hemitransposition.

Small bowel perforation from a migrated biliary stent.

Stenting of the biliary tract is performed for a variety of benign and malignant disorders. Although uncommon, proximal and distal migration of these stents is known to occur. We report a case of jejunal perforation from a distally migrated biliary stent.

Combined cardio-renal transplantation (CCRT) from the same donor: report of two cases and review of the literature.

Two patients with successful combined cardio-renal transplantation (CCRT) using allografts from the same donor are reported. Both patients underwent staged procedure with hearts being transplanted first followed by kidneys. One patient suffered simultaneous acute rejection of both allografts, indeed a very rare event, which was successfully treated with pulse steroids. Because of the successful patient and graft outcomes, we propose that staged CCRT offers a reasonable therapeutic option for patients with co-existing, irreversible cardiorenal failure.

Spontaneous rupture of the liver upon revascularization during transplantation.

Spontaneous rupture of the liver has been described in association with many benign and malignant conditions. We report, to our knowledge, the first case of spontaneous rupture of the liver upon revascularization, requiring total hepatectomy and portocaval shunt, followed by successful retransplantation. Routine pathological examination of the explanted liver failed to reveal the etiology of the rupture. However, electron microscopy demonstrated abnormal collagen in the hepatic arterial wall compatible with a collagen disorder such as Ehlers-Danlos type IV disease. We conclude that the donor liver had a previously undiagnosed collagen disorder. Review of the literature does not preclude the use of livers from donors with a history of connective tissue disorders. Based on our experience one should exercise caution when using livers from such donors. With a history of connective tissue disorder in an immediate family member, further tests should be performed in the donor to rule out a subclinical connective tissue disorder. In addition, a review of all patients reported thus far to have undergone total hepatectomy and portocaval shunt, followed by liver transplantation as a two-stage procedure is presented.

Repetitive self-limited acute pancreatitis induces pancreatic fibrogenesis in the mouse.

The role of repetitive acute injury in the pathogenesis of chronic pancreatitis remains unknown. To determine if repetitive injury induced by pancreatic hyperstimulation would reproduce the characteristic features of human chronic pancreatitis, acute reversible pancreatic injury was induced in mice by twice weekly cerulein treatment, 50 microg/kg/hr x 6 hr, for 10 weeks. Procollagen alpha1(I) mRNA was markedly increased by week 2. Sirius red staining of interstitial collagen demonstrated progressive accumulation of extracellular matrix surrounding acinar units and in interlobular spaces. Atrophy, transdifferentiation of acinar units to ductlike tubular complexes, and dilatation of intraacinar lumina also developed. Electron microscopy demonstrated the presence of stromal cells in areas of fibrosis with morphologic characteristics of pancreatic stellate cells. These findings demonstrate that, in a murine model, repetitive acute injury to the pancreas by hyperstimulation can reproduce the major morphological characteristics of human chronic pancreatitis.

Delayed graft function complicated by spontaneous renal allograft rupture without acute rejection.

We report a young male patient who developed spontaneous renal allograft rupture 7 days after cadaveric renal transplant, complicated by delayed graft function, without evidence of rejection on allograft biopsy.

Effects of tetrodotoxin and OKY-046 in renal ischemia reperfusion.

Ischemia reperfusion injury (IRI) contributes significantly to posttransplant graft dysfunction. An emphasis, therefore, has been directed toward the identification of novel renoprotective agents. In this study, the renoprotective effect of tetrodotoxin (TTX) alone, or in combination with a thromboxane synthetase inhibitor (OKY-046), was investigated in a 60-min warm ischemia, 72-h reperfusion, IRI rodent model. Unilateral nephrectomized rats were treated with the test vehicle alone, 1, 2, or 4 microgram/kg of TTX or 2 mg/kg of OKY-046 intravenously, either 15 min pre- or postischemia, or 2 microgram/kg TTX administered simultaneously with OKY-046 (2 mg/kg), following the ischemic interval. Baseline, 24, and 72 h mean plasma creatinine (Cr) and urea nitrogen (BUN) were compared. Maximal renoprotection was demonstrated by significantly improved 72-h Cr and BUN levels with the 2 microgram/kg of TTX or with 2 mg/kg of OKY-046, each administered after ischemia (ischemic control Cr = 8. 01 +/- 1.07 mg/dl vs TTX = 3.84 +/- 0.80 mg/dl, P = 0.008; vs OKY-046 = 4.0 +/- 1.5, P + 0.008; ischemic control BUN = 241.3 mg/dl +/- 32.8 vs TTX = 85.7 mg/dl +/- 18.7, P < 0.008; vs OKY-046 = 52.6 +/- 22.5, P = 0.008). The combination therapy utilizing TTX with OKY-046 resulted in reduced animal survival, demonstrating no renoprotection as measured with the biochemical parameters. These results support the renoprotective effects of TTX in a severe, rodent IRI model. The exact mechanism of action, as well as the therapeutic potential of TTX in preservation/transplantation, warrants further study.

Prognostic value of dipyridamole thallium-201 screening to minimize perioperative cardiac complications in diabetics undergoing kidney or kidney-pancreas transplantation.

To minimize perioperative cardiac events, we utilize a screening protocol consisting of intravenous dipyridamole thallium-201 myocardial imaging (DPT), with the selective use of coronary angiography based on the presence of reversible defect(s) on DPT test. A retrospective study was performed to determine the prognostic value of this protocol and to identify any clinical parameters predictive of an abnormal DPT test. To accomplish this, a detailed chart analysis of 176 consecutive kidney (n = 89) and kidney-pancreas (n = 87) transplant recipients who had undergone pretransplant DPT testing was performed. The results of the DPT test were interpreted as normal in 111, fixed defect in 15, and reversible defect(s) in 50 patients. Forty-two of the 50 patients with reversible defect(s) underwent coronary angiography. Twelve of the 27 patients with significant coronary artery disease (CAD, > 50% stenosis in one or more coronary arteries) underwent pretransplant revascularization and the remaining 15 were treated medically. Cardiac events (documented acute myocardial infarction or sudden cardiac death) within 6 wk of transplant were stratified by the results of this protocol. Also, various clinical parameters were compared between patients with normal and abnormal (fixed and reversible defect) DPT tests. Only one of the 111 (0.9%) transplant recipients with a normal DPT test had a perioperative cardiac event. None of the 15 (0%) patients with a fixed defect and none of the 15 (0%) patients with reversible defect(s), but a nonsignificant (< 50% narrowing) coronary angiogram, had a perioperative cardiac event. Three of the 27 (11.1%) patients with reversible defect(s) and significant disease on coronary angiography, who had undergone pre-transplant revascularization or were managed medically, had a perioperative coronary event. Of 14 recipients parameters analyzed, age > 50 yr was the only variable predictive of an abnormal DPT test. We conclude that the incidence of perioperative cardiac events in patients with a normal or fixed defect, or reversible defect(s) but a nonsignificant (< 50% narrowing) coronary angiogram is very low, indicating the high correlation of these findings on DPT and an uneventful (cardiac) post-transplant course. The incidence of perioperative cardiac complications amongst the high-risk transplant recipients with reversible defect(s) and significant CAD on coronary angiogram may be minimized by appropriate preoperative medical management or revascularization. None of the clinical variables except age > 50 yr was predictive of an abnormal DPT test.

Effect of octreotide on stimulated insulin release from pancreatic tissue slices.

This study was designed to investigate a possible mechanism of action by which octreotide acetate causes insulin suppression in the denervated pancreas. Canine tissue slices were placed in a pH-adjusted medium with varying concentrations of glucose and octreotide acetate: Experiment 1, 30 min in basal medium with 0.6 mg/ml glucose; Experiment 2, addition of 6.0 mg/ml glucose; Experiment 3, addition of 4 microg octreotide acetate/70 ml (comparable to 100 microg/25 kg body weight); Experiment 4, addition of 16 microg octreotide acetate/70 ml; Experiment 5, incubation with 6.0 mg glucose/ml and 4 microg octreotide acetate/70 ml; Experiment 6, incubation with 6.0 mg glucose/ml and 16 microg octreotide acetate/70 ml; Experiment 7, preincubation with 4 microg octreotide acetate/70 ml, then with 6.0 mg glucose/ml; and Experiment 8, preincubation with 16 microg octreotide acetate/70 ml, then with 6.0 mg glucose/ml. Medium levels of insulin, glucagon, and amylase were collected at intervals during the incubation periods. There was an appropriate increase in the rate of insulin release to glucose stimulation in the high-glucose (6.0 mg/ml) group. There was no significant inhibition of basal or glucose-stimulated insulin release with either simultaneous or pretreatment of the canine pancreatic tissue slices with either concentration of octreotide acetate. These studies support an indirect mechanism by which octreotide acetate exerts its inhibitory effect on endocrine and exocrine function in the canine pancreas transplant model.

Renoprotective effects of the 21-aminosteroid U74389G in ischemia-reperfusion injury and cold storage preservation.

Free radical mediated lipid peroxidation (LPO) has been implicated in the pathogenesis of ischemic-reperfusion injury (IRI). To address the renoprotective effect(s) of LPO inhibition, the efficacy of the 21 aminosteroid U74389G was evaluated in three IRI models. In Model 1 51 unilateral nephrectomized rats that underwent 60 min of warm ischemia followed by a 72-hr reperfusion interval were treated with the test vehicle only, or 3, 6, or 12 mg/kg of U74389G intravenously, 5 min pre- or postischemia. In Model 2 Sprague-Dawley rats underwent sham operation (n=9), or 45 min of warm ischemia and 10 min of reperfusion with U74389G (6 mg/kg; n=10) or test vehicle only (n=10) administered intravenously over 10 min beginning 5 min prior to clamp release. After reperfusion, LPO was determined by assay of snap frozen tissue for thiobarbituric acid (TBA) concentrations (nmol/g tissue weight). In Model 3 domestic lean maid pigs (14-18 kg) underwent left nephrectomy with 30 min of warm ischemia, Collins C-4 flush, and 24 hr of cold storage preservation. Heterotopic autotransplantation and immediate contralateral nephrectomy was then performed in Group A-nonischemic controls (n=4), Group B-ischemic controls (n=5), and Group C-U74389G (6 mg/kg) administered preischemia and at autotransplantation (n=5). In Model 1 maximal renoprotection was demonstrated with the 6 mg/kg dose of U74389G administered after ischemia (ischemic control 72-hr serum creatinine (Cr) = 8.01+/-1.1 mg% vs. 3.32+/-0.96 mg%; ischemic control creatinine clearance = 0.069+/-0.03 ml/min vs. 0.206+/-0.04 ml/min; P<0.05). In Model 2 TBA levels were significantly lower in U74389G treated animals (88.5+/-10.0 vs. ischemic controls = 296.8+/-81.4; P=0.02). In Model 3 graft survivals were 100%, 0%, and 60% respectively. Peak Cr and BUN (mg%) were significantly greater in Group C vs. Group A, (Group A Cr = 8.59+/-0.63 vs. Group C = 12.8+/-1.01; Group A BUN = 64.1+/-2.73 vs. Group C = 104.9+/-12.21)--however, by day 10, thee were no significant differences in renal function: (Group A Cr = 2.15+/-0.3 vs. Group C = 2.10+/-0.06; Group A BUN = 27.0+/-6.0 vs. Group C = 31.1+/-6.4). These results support the beneficial effects of LPO inhibitors in models of ischemia-reperfusion, as well as preservation/transplantation, and suggest that this renoprotection correlates with decreased membrane lipid peroxidation.

Effect of somatostatin and octreotide acetate on OP-CCK-stimulated exocrine secretion in the denervated canine pancreas.

Somatostatin and its analogue, octreotide acetate (Sandostatin), have been demonstrated to suppress exocrine secretion in a denervated canine pancreatic autograft model. To help define this inhibitory mechanism, the effect of these agents on cholecystokinin (CCK)-stimulated acinar cell secretion was evaluated. In vitro assessment evaluated the effect of somatostatin on octapeptide (OP)-CCK-stimulated amylase release of pancreatic tissue slices. In vivo assessment employed animals with pancreatic autografts and pancreaticocystostomies, evaluating the effect of a bolus intravenous injection of 100 micrograms of octreotide acetate on the basal and OP-CCK-stimulated (125 ng/kg/h) secretion of urinary (autograft) amylase and bicarbonate. Incubation of tissue slices with 0.16, 0.24, or 0.32 microgram/ml somatostatin had no significant effect on in vitro OP-CCK-simulated amylase release. Intravenous octreotide acetate resulted in a significant decrease in the basal rate of amylase secretion but had no significant effect on OP-CCK-stimulated autograft amylase or bicarbonate release. These studies demonstrate that octreotide acetate has an in vivo inhibitory effect on basal amylase release of pancreatic autografts but cannot counteract maximal stimulation with exogenous OP-CCK. Also, somatostatin does not inhibit OP-CCK-stimulated acinar cell secretion of pancreatic tissue slices. These results indicate that the exocrine inhibition produced by somatostatin analogues in the grafted pancreas occurs via an indirect mechanism.

Effect of L-364,718 on pancreatic endocrine function following partial pancreatectomy.

This study was designed to determine the effect of a potent cholecystokinin antagonist, L-364,718, on canine pancreatic endocrine function following partial pancreatectomy. Plasma glucose, insulin, and glucagon were determined over a 2-hr interval following an intravenous bolus of 0.5 g/kg glucose in a 50% solution. The following groups were established: normal animals (group A, n = 5), normal animals pretreated with 20 nmole/kg L-364,178 (group B, n = 5), partially pancreatectomized animals (group C, n = 5), and partially pancreatectomized animals pretreated with 20 nmole/kg L-364,178 (group D, n = 5). In contrast to animals with an intact pancreas, pretreatment with L-364,718 following partial pancreatectomy resulted in a significant decrease in peak insulin (group C = 132.8 +/- 13.0 microU/ml vs Group D = 90.4 +/- 16.1 microU/ml, P < 0.05) and the basal-to-peak insulin difference (group C = 111.9 +/- 11.5 microU/ml vs group D = 77.5 +/- 16.6 microU/ml, P < 0.05). Despite this, the rate of glucose utilization (K value) was significantly increased in the partially pancreatectomized animals given the antagonist (group C = -1.22 +/- 0.22%/min vs group D = -2.79 +/- 0.427%/min) and there were no significant differences in basal or peak glucose when comparing the groups given L-364,718 with the groups given placebo (group A vs B and group C vs D). Thus, the CCK antagonist L-364,718 significantly decreases peak insulin in partially pancreatectomized animals but not in nonoperative control animals. There is a paradoxical increase in the rate of glucose utilization but no effect on glucose homeostasis. The effect of this antagonist in other models of reduced islet cell reserve (i.e., pancreas transplantation) remains to be determined.

Pancreaticocystostomy revision for obstructive pancreatitis and pancreatic fistula after segmental pancreatic transplantation.

Combined kidney-pancreas transplantation is an effective surgical therapy for end-stage renal failure secondary to type I diabetes mellitus. However, obstructive pancreatitis and pancreaticocutaneous fistula remain significant postoperative complications unique to extraperitoneal segmental pancreatic transplantation. We present our experience with 13 patients (7 with obstructive pancreatitis and 6 with pancreaticocutaneous fistulae) after segmental extraperitoneal pancreatic transplantation, who subsequently underwent intraperitoneal reconstruction of the pancreaticocystostomy. This reconstruction was successful in 11 of 13 (85%) patients with minimal morbidity and no mortality. This intraperitoneal approach to reconstruction of the pancreaticocystostomy after segmental extraperitoneal pancreatic transplantation is a safe and effective means of graft salvage and this technique has not been described in the literature.