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Biomedical subjects

S Lindgren

Publications and source records attributed to S Lindgren.

At least 37 records · Page 2Linked to original sources
PubMed2001

Chronic infusion of nicotine can increase operant self-administration of alcohol.

Effects of nicotine, administered by continuous infusion via osmotic minipumps, were studied on the operant self-administration of alcohol by rats, using a variable interval (15 s) schedule, and measuring the acquisition, maintenance, extinction and reinstatement of responding for alcohol. Doses of nicotine of 0.25, 1.25 and 7.5 mg/kg/24 h had no significant effects on the maintenance of responding for alcohol, but 5 mg/kg/24 h nicotine resulted in a significant increase in responding on the lever delivering the reward when water was substituted for the alcohol, indicating delayed extinction of responding. During infusion of 2.5 mg/kg/24 h nicotine, responding was significantly greater over the "sucrose-fading" training sessions, during acquisition of responding, when mixtures of alcohol and sucrose were provided as reward. When minipumps infusing 2.5 mg/kg/24 h nicotine were implanted after the alcohol responding had been acquired, the responding for alcohol increase during the first week of nicotine infusion, but corresponding nicotine infusion doses of 0.25, 1.25 and 7.5 had no significant effects. The results indicate that nicotine can increase operant responding for alcohol and this is crucially dependent on the dose of nicotine and the time of testing. The results have implications for the frequently encountered dependence on the combination of alcohol and nicotine.

Alcohol Drinking↗
PubMed2001

Future development of general internal medicine: a Swedish perspective.

Over the past decade, the demands on internal medicine have increased markedly, partly due to an increasing number of elderly patients with multiple diseases. About half of all the cases coming into the emergency units of Swedish hospitals are related to internal medicine, while planned admissions account for only 10% of in-patient care. In our opinion, the fundamental cause of the strained situation in the health care service today is the fact that the emergency care responsibility of internal medicine is not clearly delimited. This means that the specialty must attend to problems in health care that the other health and sick-care services cannot cope with. Furthermore, an overly extensive division of the discipline of internal medicine into subspecialties can lead to inferior treatment of elderly patients with multiple diseases, as well as to increased costs. We believe that an umbrella organisation with overall management of independent subspecialties would make it possible to meet the increased need for internal medicine in a flexible way. In addition, internal medicine could widen its area of responsibility in the border region to surgery, while the demarcation to other specialties in the emergency unit, including primary care, is already very clear today, and should remain so.

Journal Article↗
PubMed2001

Warning! Suctioning. A lung model evaluation of closed suctioning systems.

BACKGROUND: Closed system suctioning, CSS, has been advocated to avoid alveolar collapse. However, ventilator manufacturers indicate that extreme negative pressure levels can be obtained during closed system suctioning, impeding the performance of the ventilator. METHODS: Suctioning with a 12 or 14 Fr catheter with a vacuum level of -50 kPa was either performed with an open technology or a CSS, where the catheter is introduced through a tight-fitting connection through the endotracheal tube, EYT. The lung model was ventilated with a Servo 900C or 300 ventilator with an I:E ratio of 1:2, 1:1 and 2:1 and extrinsic positive end-expiratory pressure (PEEP) at 0 or 10 cm H20. Respiratory volumes and alveolar pressure were measured at the lung model alveolus. RESULTS: The initial suctioning flow was >40 l/min with a 14 Fr catheter. When inserting the catheter through a no. 7 ETT, PEEP rose from 11 to 23 cm H2O during volume control ventilation with an I:E ratio 1:1. During suctioning the alveolar pressure fell to 10 cm H2O below the set PEEP level. CSS during pressure control ventilation had fewer effects. Low tidal volumes, inverse I:E ratio and secretions in the tube resulted in pressures down to -92 cm H2O. CONCLUSION: CSS should not be used in volume control ventilation due to risk of high intrinsic PEEP levels at insertion of the catheter and extreme negative pressures during suctioning. Pressure control ventilation produces less intrinsic PEEP effect. The continuous positive airway pressure (CPAP) mode offers the least intrinsic PEEP during insertion of the catheter and least sub-atmospheric pressure during suctioning.

Air Pressure↗
PubMed2001

Clinical spectrum of hepatitis C-related liver disease and response to treatment with interferon and ribavirin in haemophilia or von Willebrand disease.

Our aim was to evaluate the severity of liver disease resulting from chronic hepatitis C in haemophilia or von Willebrand disease and the efficacy of 6 months treatment with interferon alpha and ribavirin. Fifty-five liver biopsies were performed in 43 patients without any bleeding complications, as seen with ultrasound immediately after the biopsy and 48 h thereafter. Histological changes were mild, with low scores for both inflammation and fibrosis, in spite of long exposure to blood products (mean 27 years). Two patients had compensated cirrhosis. Thirty-five out of 39 included patients completed study treatment. Hepatitis C virus (HCV)-RNA was negative in 77% (30/39) of patients at the end of treatment, and 36% (14/39) achieved a complete sustained response at follow-up 6 months after treatment. Treatment failure was more frequent in patients with virus genotype 1 compared with non-1 (P = 0.0003). The response rate correlated well with that of non-haemophilic patients. In summary: (1) liver biopsy was safe with our regimen; (2) liver disease in our patients was usually mild and had a slow progress; (3) only HCV genotype 1 predicted treatment failure; (4) our treatment results agreed with those from non-haemophilic patients.

Adolescent↗
PubMed2001

GB virus C/hepatitis G virus infection in patients investigated for chronic liver disease and in the general population in southern Sweden.

Serum samples from patients referred for liver biopsy for investigation of suspected chronic liver disease (n = 286) and from healthy middle-aged volunteers (n = 445) were analyzed for markers of exposure to GB virus C/hepatitis G virus (GBV-C/HGV), hepatitis B virus and hepatitis C virus. GBV-C/HGV analyses included GBV-C/HGV PCR for detection of viremia and GBV-C/HGV enzyme-linked immunosorbent assay for anti-GBV-C/HGV E2 antibodies. Liver biopsies were re-evaluated by a hepatopathologist. GBV-C/HGV markers were detected in 97/286 (34%) patients (GBV-C/HGV RNA = 26; anti-GBV-C/HGV E2 antibodies = 74) compared to 86/445 (19%; p < 0.0001) controls (GBV-C/HGV RNA = 7, anti-GBB-C/HGV E2 antibodies = 79). A significantly higher proportion of GBV-C/HGV-exposed subjects in the patient group were viremic compared to controls (27% vs. 8.1%; p = 0.0015). GBV-C/HGV markers were more commonly found in patients with chronic hepatitis B and C. In patients with GBV-C/HGV viremia, a higher occurrence of bile duct degeneration was detected than in non-viremic patients. Markers of GBV-C/HGV infection were over-represented among patients investigated for chronic liver disease, and ongoing GBV-C/HGV viremia was more common in this group than in controls. Apart from a higher prevalence of bile duct degeneration in viremic patients, infection with GBV-C/HGV did not confer any specific histological characteristics.

Biomarkers↗
PubMed2001

HIV-1 in placentas of untreated HIV-1-infected women in relation to viral transmission, infectious HIV-1 and RNA load in plasma.

The presence of HIV in the placenta was analysed in relation to virological and immunological factors and vertical transmission of HIV in 39 pregnancies between 1989 and 1993 among 37 HIV-1-infected women without zidovudine prophylaxis. HIV-1 was detected in 12 of 37 (31%) placentas by immunohistochemistry and in 3 of 18 by PCR. Altogether 14/39 (36%) placentas bore evidence of HIV-1 infection, although there was no relation with the outcome of HIV infection in the child. Neither was there a relation between placental infection and either CD4 cell counts or HIV-1 RNA levels. However, HIV-1 was isolated from plasma in 20 of 39 (50%) pregnancies, which was inversely related to the presence of HIV in the placenta. When HIV-1 was identified in the placenta, HIV-1 was isolated from plasma in 3/14 (21%) pregnancies, vs 17/25 (68%) when it was not (p = 0.01), with a relative risk of having a placenta positive for HIV of 3.9 in pregnancies with a negative plasma HIV isolation. This inverse relation may point to differences in tropism between HIV-1 in placenta and plasma. The results show that the placental barrier prevents HIV transmission, irrespective of whether HIV enters the placenta or not.

CD4 Lymphocyte Count↗
PubMed2001

Short and long term outcome of severe acute pancreatitis.

OBJECTIVE: Between 1985 and 1994, 883 cases of acute pancreatitis were treated in Malmö, Sweden (population 233,000). The purpose of this study was to report the short- and long-term outcome of the 79 cases that were severe, according to the Atlanta classification. DESIGN: Retrospective and follow-up study a median time of 7 years since the attack. SETTING: University hospital, Sweden. SUBJECTS: 79 patients with severe acute pancreatitis. MAIN OUTCOME MEASURES: Mortality, cause of death, organ failure, local complications, surgical procedures, mortality since the attack, and endocrine and exocrine dysfunction. RESULTS: Twenty-one patients died from their attack. Organ failure was the predominant cause of death in the 13 patients who died during the first 10 days after admission, whereas infection was the most common cause of death in patients who died later. Mortality was low under the age of 60 and increased with age. Organ failure developed in 72 patients. Twenty-four patients developed pancreatic necrosis or abscesses and 18 patients were treated by necrosectomy and open or closed drainage. At follow-up, 13 patients had died, 2 from pancreatic carcinoma. 35 patients were included in the follow-up survey. 15 of these had diabetes and an additional 4 had impaired glucose tolerance. 9 patients had signs of severe exocrine dysfunction. CONCLUSIONS: There was a high incidence of endocrine and exocrine dysfunction together with, in many patients, ongoing social problems related to chronic alcoholism several years after an attack of severe acute pancreatitis.

Abdominal Pain↗
PubMed2001

Effects of differently oxidized LDL on the expression of pro-inflammatory molecules in human monocytes in vitro.

The oxidation of low-density lipoprotein (LDL) is thought to be a major contributor to the development of atherosclerosis and considerable evidence has accumulated showing that oxidized LDL (ox LDL) induces cell damage and pro-atherogenic events. However, evidence that oxidized LDL directly causes atherosclerosis is lacking. We studied whether native and enzymatically or chemically ox LDL at concentrations of 5 and 100 microg/mL is cytotoxic to or promotes pro-atherogenic activation of human primary monocytes in culture. Both types of ox LDL (100 microg/mL), but not native LDL added to monocytes for 24 h significantly diminish DNA synthesis and increase cell death. In addition, both preparations of ox LDL inhibit cytokine and metalloproteinase production, diminish cellular oxygen consumption and induce PPAR gamma expression. Enzymatically ox LDL, but not LDL oxidized by copper sulfate, also increases the monocyte metabolic rate and induces intracellular lipid accumulation. Low concentrations of either preparation of oxidized and native LDL did not show significant effects on all parameters measured. These data establish a direct link between ox LDL concentration and cytotoxicity and suggest that oxidation by copper of the lipid moiety in LDL and of the protein moiety by enzyme creates ox LDL, which can damage monocytes without release of pro-inflammatory molecular species. In contrast to native and enzymatically ox LDL, copper ox LDL does not induce intracellular lipid accumulation. Differently oxidized LDL molecules may exert distinct effects in lesion development in atherosclerosis.

Cell Death↗
PubMed2000

Pravastatin down-regulates inflammatory mediators in human monocytes in vitro.

There is experimental evidence that pravastatin, which is designed to inhibit the rate-limiting enzyme of cholesterol synthesis, can affect cell metabolism and proliferation. We therefore studied the effects of pravastatin on the generation of inflammatory mediators in non-stimulated and stimulated primary human monocytes in vitro. In our experimental model, pravastatin induced a dose-dependent inhibition of monocyte cholesterol synthesis (up to 67%), up-regulation of low density lipoprotein receptor mRNA (by about 35%) and reduction in intracellular cholesterol accumulation. In parallel, exposure of non-stimulated monocytes to various doses of pravastatin resulted in inhibition of monocyte chemoattractant protein-1 protein expression (up to 15-fold), reduction of tumour necrosis factor alpha (TNF-alpha) levels (up to 2.4-fold) and a total loss of metalloproteinase-9 activity in stimulated cells. Pravastatin at concentrations of 5, 100 and 500 microM caused an inhibition of TNF-alpha-induced cellular oxygen consumption from 2. 4- to 5.5-fold. These data extend the findings of potential anti-inflammatory actions of statins and also suggest the possibility for pravastatin use in a broader spectrum of inflammatory situations.

Chemokine CCL2↗
PubMed2000

[Mother-to-child transmission of HIV infections. Antiviral agents and Cesarean section reduce the risk of transmission].

There has been a substantial decrease in maternal-infant transmission of HIV in many European and North American countries during the past five years, from 15-25 per cent to approximately 5%. Reasons include the prophylactic administration of zidovudine to mother and child, more effective treatment strategies leading to decreased viral load during pregnancy, and increased use of elective Caesarean section. In developing countries however, the vertical transmission rate of HIV is still high at 25-40 per cent. Simpler and less expensive prophylactic regimens, such as nevirapine to mother and child at delivery and after birth, respectively, have raised hope. Drug resistance and the risk of adverse effects of antiretroviral drugs on the child are threats to the prevention of mother-to-infant transmission of HIV.

Anti-HIV Agents↗
PubMed2000

The carboxyl-terminal fragment of alpha1-antitrypsin is present in atherosclerotic plaques and regulates inflammatory transcription factors in primary human monocytes.

alpha1-Antitrypsin (AAT) serine proteinase inhibitor is found in most biological fluids, diffuses into most tissues, and is an important factor in controlling tissue damage by proteases in inflammatory diseases such as atherosclerosis. We have previously reported that the C-terminal fragment (C-36) generated during the cleavage of AAT by proteinases forms amyloid fibrils which have biological effects unrelated to precursor functions. Here we show that the C-36 fragment is present in atherosclerotic plaques, particularly within the fibrous cap at the base of the lipid core. We also found that human monocyte stimulation with C-36 fibrils led to a strong activation of both peroxisome proliferator-activated receptors alpha and gamma (PPARalpha and PPARgamma) at 1, 2, and 18 h of cell culture. A parallel increase in the intracellular lipid accumulation was also observed. Furthermore, stimulation of monocytes with C-36 for 18 h led to activator protein-1 (AP-1) and nuclear factor-kappaB (NF-kappaB) activation. These data for the first time demonstrate the peptide of AAT as a component of atherosclerotic plaques and as a novel activator of PPARalpha, PPARgamma, NF-kappaB, and AP-1 in cultured monocytes. Taken together, the effects of the peptide represent a new mechanism of monocyte activation that may be of importance not only in atherogenesis, but also in other inflammatory processes.

Arteriosclerosis↗
PubMed2000

Basilar artery occlusion in a child: "clot angioplasty" followed by thrombolysis.

Basilar artery occlusions are rare but have a very poor prognosis. Intra-arterial thrombolysis may produce recanalization and better clinical outcome. A short delay between the onset of symptoms and thrombolysis is considered essential for successful recanalization and for the smallest possible risk of haemorrhagic complications. We present a case of basilar artery occlusion in an 8-year-old child, which was treated by "clot angioplasty" followed by intra-arterial thrombolysis. Thirty hours after progressive alteration of consciousness, speech disturbances and left arm paresis, the child became comatose with decerebrate rigidity. A CT scan showed parenchymal ischaemic lesions. Angiography (performed 36 h after the onset of symptoms) showed a total occlusion of the basilar artery. A clot angioplasty was performed by placing a balloon catheter within the thrombus and inflating it several times in the occluded segment of the basilar artery. Thrombolysis was then performed through the balloon catheter. The basilar artery was only partially recanalized at the end of the procedure, but the perforating arteries of the brain stem had reappeared on angiography. Three months later the child had completely recovered to a normal clinical status. In conclusion, the very poor natural prognosis of basilar artery occlusion requires aggressive management. Recanalization of the basilar artery may be performed even late after the onset of symptoms. Clot angioplasty allows partial recanalization, which may increase the efficiency of thrombolysis.

Acute Disease↗
PubMed2000

Involvement of the entire spinal cord and medulla oblongata in acute catastrophic-onset transverse myelitis in SLE.

A 30-year-old Caucasian male with systemic lupus erythematosus suffered acute catastrophic-onset transverse myelitis. Two years earlier aseptic meningitis, another rare CNS lupus manifestation, had been diagnosed. MRI showed involvement of the medulla oblongata and the entire spinal cord. Therapy with intravenous high-dose methylprednisolone and intravenous cyclophosphamide is discussed.

Acute Disease↗
PubMed2000

Anti-neutrophil cytoplasmic antibodies in patients with chronic liver diseases: prevalence, antigen specificity and predictive value for diagnosis of autoimmune liver disease. Swedish Internal Medicine Liver Club (SILK)

BACKGROUND: Anti-neutrophil cytoplasmic antibodies (ANCA) against proteinase 3 are diagnostic of Wegener's granulomatosis, but ANCA occur also in patients with other inflammatory disorders, such as ulcerative colitis, primary sclerosing cholangitis (PSC) and autoimmune hepatitis. As their predictive value for autoimmune liver disease remains unknown, we analysed the prevalence and antigen specificity of ANCA in patients with various chronic liver diseases (CLD). METHODS: We studied sera from 100 patients with primary biliary cirrhosis (PBC), from 76 with PSC and from 279 with various CLD, consecutively drawn during a 5-year period at the time of liver biopsy. The ANCA were detected by indirect immunofluorescence (IIF) while the antigen specificity was characterized by ELISA by using lactoferrin, neutrophil elastase, cathepsin G and BPI (bactericidal/permeability increasing protein) as antigens. RESULTS: In PBC, ANCA were detected by IIF in 39 patients (39%). The antigen reactivity by ELISA was lactoferrin in seven, elastase in 15, BPI in 20 and cathepsin G in four patients. Four patients had reactivity against more than one antigen. In PSC, IIF demonstrated ANCA in 49 patients (65%). The antigen reactivity was lactoferrin in 17, elastase in 14, BPI in 20 and cathepsin G in four patients. Twelve patients showed reactivity against more than one antigen. In CLD, ANCA were observed in sera from 55 patients (20%). Nineteen of 45 patients (42%) with autoimmune liver disease were ANCA positive versus 36/234 (15%) with non-autoimmune liver disease (P = 0.0002). Among IIF-positive patients, antibody reactivity against lactoferrin was noted in 14, elastase in 28, BPI in 25 and cathepsin G in five patients. Twenty-one patients had reactivity against more than one antigen. Elastase and BPI antibodies occurred more frequently in patients with autoimmune compared to non-autoimmune liver disease (P < 0.01). CONCLUSIONS: Anti-neutrophil cytoplasmic antibodies are prevalent in patients with chronic liver diseases, but although they occur more frequently in patients with autoimmune liver disease their specificity and sensitivity for autoimmune liver disease is low. The predominant antigens are lactoferrin, elastase and BPI, but the correlation between IIF findings and ELISA reactivity against these antigens is weak.

Antibodies, Antineutrophil Cytoplasmic↗
PubMed2000

Prevalence and clinical spectrum of chronic viral hepatitis in a middle-aged Swedish general urban population.

BACKGROUND: Although abundant data are available regarding the prevalence of chronic hepatitis B or C virus (HBV, HCV) among both blood donors and patients with liver diseases, corresponding data for the general population are scarce. Accordingly, this study was designed to investigate the prevalence and clinical spectrum of HBV and HCV in a general Swedish middle-aged urban population. METHODS: Demographic data and blood samples were collected from subjects enrolled in a prospective study of cancer development in the city of Malmö (population 250,000). The participation rate in the preliminary examination was 46.2%. From 12,445 individuals born between 1926 and 1945 and included in the study, a statistically representative subsample of 6103 persons was selected. Blood samples were available from 5533 of these. The mean age of the subjects in the series was 58.5 +/- 5.9 years, and 59% were women. The HBV markers used were anti-HBc and HBsAg. HCV antibodies were detected with a third generation anti-HCV ELISA, followed by immunoblotting (RIBA 3) if the test was positive. Immunoblot-reactive samples were analysed for HCV-RNA by polymerase chain reaction and genotyped. In all patients with signs of chronic HBV or HCV, epidemiological data were evaluated and liver biopsies obtained. RESULTS: Of the series as a whole (n = 5533), 4.2% (n = 211) tested positive for anti-HBc and 0.2% (n = 10) for HBsAg. RIBA 3 analysis showed 0.37% (18/5533) to be anti-HCV-positive, of whom 83% (15/18) were HCV-RNA-positive. Apart from two (both from HBsAg carriers) with normal histology, all liver biopsies manifested various degrees of inflammation and fibrosis. Among anti-HCV-positives, median grade was 6 and median stage 1 (Knodell score). CONCLUSION: The prevalence of both chronic HBV and HCV is low in the Swedish general urban middle-aged population. Nonetheless, the long-term effects on the population and the health care system may be significant.

Female↗
PubMed2000

Inflammatory bowel disease promotes venous thrombosis earlier in life.

BACKGROUND: Patients with inflammatory bowel disease (IBD) may be at increased risk of having venous thromboembolism. METHODS: Medical records from 1,253 IBD patients attending hospital care during the years 1987-97 were studied. These patients were recruited from a population of 340,000 inhabitants. Patients with verified venous thrombosis were characterized clinically, and blood samples were examined for coagulopathy including analyses of antithrombin, plasminogen, protein C, protein S, factor V, and prothrombin mutations. As control groups we used 99 patients with verified venous thrombosis and no history of IBD and 288 volunteers with no history of thrombosis. RESULTS: The incidence of venous thrombosis was 1.5/1,000 IBD patients per year, which is comparable to the background population. The mean age was significantly lower in IBD patients than in non-IBD patients (53 versus 64 years, P= 0.0225). We found one patient with antithrombin deficiency but none with protein C, protein S, or plasminogen deficiency. Factor V mutation was as prevalent in IBD patients with thrombosis as in thrombotic non-IBD patients (27% versus 28%) and 3.0 times (95% confidence interval, 0.8-11.9) more frequent in IBD patients with thrombosis than in healthy controls. Prothrombin mutation was not detected in IBD patients with venous thrombosis. CONCLUSION: We found no increased incidence of venous thrombosis in IBD patients compared with a background population. However, IBD patients had venous thrombosis earlier in life than non-IBD patients. Although factor V mutation may contribute to thrombosis, IBD acts as a trigger through mechanisms that still remain unexplained.

Adolescent↗