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Biomedical subjects

K P Bouter

Publications and source records attributed to K P Bouter.

At least 19 recordsLinked to original sources
PubMed2006

Infection induced inflammation is associated with erectile dysfunction in men with diabetes.

BACKGROUND: In diabetic patients with erectile dysfunction, endothelial dysfunction is a major underlying cause. Infection-induced inflammation may be associated with endothelial dysfunction. The goal of this study was to determine whether erectile dysfunction in patients with diabetes is associated with infections of Chlamydia pneumoniae or cytomegalovirus and/or with low-grade inflammation. MATERIALS AND METHODS: Diabetic patients, 57 with and 33 without erectile dysfunction, were enrolled in a case-control study. Both groups of patients consists of type 1 and type 2 diabetics. Serum antibodies against cytomegalovirus and C. pneumoniae and markers of inflammation, including high-sensitivity C-reactive protein and fibrinogen, were measured. RESULTS: Adjusted odds ratios for erectile dysfunction in cytomegalovirus IgG, C. pneumoniae IgG and C. pneumoniae IgA seropositive men were 2.4 (95%CI; 1.0-6.0), 3.0 (95%CI; 1.2-8.1) and 1.8 (95%CI; 0.7-4.6), respectively. Odds ratios for the highest tertiles of high-sensitivity C-reactive protein and fibrinogen concentrations compared to the lowest tertile were 4.3 (95%CI; 1.4-13.1) and 6.6 (95%CI; 2.1-21.2), respectively. CONCLUSION: Elevated high-sensitivity C-reactive protein or fibrinogen serum levels and infection with cytomegalovirus or C. pneumoniae were associated with erectile dysfunction in diabetes. The relation between cytomegalovirus and erectile dysfunction is markedly present in patients with elevated high-sensitivity C-reactive protein and fibrinogen levels, suggesting a modifying effect by the inflammation.

Antibodies, Bacterial↗
PubMed2006

Comparison of the effects of continuous subcutaneous insulin infusion (CSII) and NPH-based multiple daily insulin injections (MDI) on glycaemic control and quality of life: results of the 5-nations trial.

AIMS: The goal of the study was to determine whether continuous subcutaneous insulin infusion (CSII) differs from a multiple daily injection (MDI) regimen based on neutral protamine hagedorn (NPH) as basal insulin with respect to glycaemic control and quality of life in people with Type 1 diabetes. METHODS: The 5-Nations trial was a randomized, controlled, crossover trial conducted in 11 European centres. Two hundred and seventy-two patients were treated with CSII or MDI during a 2-month run-in period followed by a 6-month treatment period, respectively. The quality of glycaemic control was assessed by HbA(1c), blood glucose values, and the frequency of hypoglycaemic events. For the evaluation of the quality of life, three different self-report questionnaires have been assessed. RESULTS: CSII treatment resulted in lower HbA(1c) (7.45 vs. 7.67%, P < 0.001), mean blood glucose level (8.6 vs. 9.4 mmol/l, P < 0.001) and less fluctuation in blood glucose levels than MDI (+/- 3.9 vs. +/- 4.3 mmol/l, P < 0.001). There was a marked reduction in the frequency of hypoglycaemic events using CSII compared with MDI, with an incidence ratio of 1.12 [95% confidence interval (CI): 1.08-1.17] and 2.61 (95% CI: 1.59-4.29) for mild and severe hypoglycaemia, respectively. The overall score of the diabetes quality of life questionnaire was higher for CSII (P < 0.001), and an improvement in pump users' perception of mental health was detected when using the SF-12 questionnaire (P < 0.05). CONCLUSION: CSII usage offers significant benefits over NPH-based MDI for individuals with Type 1 diabetes, with improvement in all significant metabolic parameters as well as in patients' quality of life. Additional studies are needed to compare CSII with glargine- and detemir-based MDI.

Adult↗
PubMed2005

Azithromycin reduces Chlamydia pneumoniae-induced attenuation of eNOS and cGMP production by endothelial cells.

BACKGROUND: Intracellular infections with cytomegalovirus (CMV) or Chlamydia pneumoniae (Cp) may play a role in the aetiology of atherosclerosis. Nitric oxide (NO) is a key regulator of endothelial function. Under pathological conditions uncoupling of endothelial nitric oxide synthase (eNOS) leads to vessel damage as a result of production of oxygen radicals instead of NO. We hypothesized that infection-induced atherosclerosis is initiated by changes in NO metabolism and may be reversed by azithromycin treatment. METHODS: Confluent human umbilical vein endothelial cells (HUVECs) were infected with Cp or CMV. After 48 h of infection, production of eNOS, cyclic guanosine monophosphate (cGMP) and reactive oxygen species (ROS) was measured. Detection of cGMP was used as a reporter assay for the bioavailability of NO. Subsequently, Cp- and CMV-infected HUVECs were coincubated with 0.016 mg L(-1) and 1 mg L(-1) azithromycin. RESULTS: Infection with Cp (MOI 1 and MOI 0.1) and CMV (MOI 1) caused a dose- and time-dependent reduction of eNOS production in the HUVECs: Cp MOI 1: 1141 +/- 74 pg mL(-1) (P < 0.01); Cp MOI 0.1: 3189 +/- 30 pg mL(-1) (P < 0.01); CMV: 3213 +/- 11 pg mL(-1) (P < 0.01) vs. 3868 +/- 83 pg mL(-1) for uninfected HUVECs. Chlamydia pneumoniae- but not CMV-infection also reduced cGMP-production (Cp: 0.195 +/- 0.030 pmol mL(-1) (P < 0.01); CMV: 0.371 +/- 27 pmol mL(-1) (P > 0.05) vs. 0.378 +/- 0.019 pmol mL(-1) for uninfected HUVECs). CMV-infection did not affect ROS production either, but Cp-infection reduced ROS-production by 21% (P > 0.05; Cp MOI 0.1) to 68% (P < 0.01; Cp MOI 1). Azithromycin treatment restored Cp-induced eNOS, cGMP and ROS production in a dose-dependent manner. CONCLUSIONS: Infection with Cp in endothelial cells in vitro attenuates eNOS, cGMP and ROS production in HUVECs and azithromycin reverses Cp-induced effects on eNOS, cGMP and ROS-production. The results from our in vitro research support the role of antibiotic therapy for infection-induced atherosclerosis by indicating that azithromycin does actually improve endothelial function.

Anti-Bacterial Agents↗
PubMed2002

Procoagulant and inflammatory response of virus-infected monocytes.

BACKGROUND: Monocytes play a prominent role in inflammation, coagulation and atherosclerosis by their ability to produce tissue factor (TF) and cytokines. The aim of the present study was to establish whether virus-infected monocytes initiate coagulation. In addition, the production of cytokines by monocytes may accelerate the chronic process of atherosclerosis and may contribute to coronary syndromes by eliciting plaque instability. MATERIALS AND METHODS: Monocytes were isolated by Vacutainer(R), BD Biosciences, Alphen aan den Rijn, Netherlands and subsequent magnetic cell sorting (MACS(R), Milteny Biotec, Bergish Gladbach, Germany). Coagulation times in normal pooled plasma and Factor VII-deficient plasma were measured after infection with cytomegalovirus (CMV), Chlamydia pneumoniae (Cp) and influenza A\H1N1. Anti-TF antibodies were added to neutralize TF expressed on monocytes. Interleukins (IL) 6, 8 and 10 were measured in the supernatants. RESULTS: Chlamydia pneumoniae- and CMV-infected monocytes decreased the clotting time by 60%, and influenza-infected monocytes by 19%, as compared to uninfected monocytes. Procoagulant activity was absent when Factor VII-deficient plasma or anti-TF antibodies were used. Monocytes produced both IL-6 and IL-8 after infection with CMV (317 pg mL-1 and 250 pg mL-1) or Cp (733 pg mL-1 and 268 pg mL-1). Similar results were obtained for influenza virus-infected monocytes, but the levels of both cytokines were 3-5-fold higher (1797 pg mL-1 and 725 pg mL-1). Interleukin-10 was not produced by infected monocytes. CONCLUSION: The procoagulant activity of virus-infected monocytes is TF-dependent. Although influenza infection did not generate a significant reduction in clotting time, the pronounced expression of IL-6 and IL-8 may induce local and/or systemic inflammatory reactions, which may be associated with plaque rupture and atherosclerosis. The lack of production of the anti-inflammatory cytokine IL-10 may even accelerate these processes.

Antibodies↗
PubMed2000

Rapid and short-acting mealtime insulin secretion with nateglinide controls both prandial and mean glycemia.

OBJECTIVE: The objective of the study was to assess the efficacy and safety of four fixed doses of nateglinide compared with placebo in the treatment of patients with type 2 diabetes with focus on the prandial state. RESEARCH DESIGN AND METHODS: This randomized double-blind placebo-controlled multicenter study was conducted in 289 patients who received either nateglinide at doses of 30 mg (n = 51), 60 mg (n = 58), 120 mg (n = 63), or 180 mg (n = 57) or placebo (n = 60) before three main meals for 12 weeks. Levels of HbA1c, fasting plasma glucose (FPG), fructosamine, and plasma lipids were measured at predetermined intervals, and the effects of nateglinide on prandial glucose insulin, C-peptide, and triglyceride levels were measured after a liquid standard meal (Sustacal; Mead Johnson, Evansville, IN). Adverse events and hypoglycemic episodes were recorded. RESULTS: After a liquid meal challenge, nateglinide rapidly increased mealtime insulin levels within 30 min of drug intake and reduced mealtime glucose excursions without affecting triglyceride levels. At study end point, reduction of HbA1c levels was statistically significantly greater with nateglinide at doses of 60, 120, and 180 mg than placebo (-0.45, -0.62, and -0.64%, respectively; P<0.05). The mean level of FPG was significantly reduced versus placebo in the nateglinide 120-mg group only (-1.14 mmol/l P<0.01). Overall, nateglinide was well tolerated. CONCLUSIONS: This study demonstrated that nateglinide improves mealtime and mean glycemic control in a dose-dependent manner by restoring early insulin secretion phase. Nateglinide was well tolerated and is suitable for the treatment of patients with type 2 diabetes.

Adult↗
PubMed2000

Asymptomatic bacteriuria may be considered a complication in women with diabetes. Diabetes Mellitus Women Asymptomatic Bacteriuria Utrecht Study Group.

OBJECTIVE: To study the prevalence of and risk factors for asymptomatic bacteriuria (ASB) in women with and without diabetes. RESEARCH DESIGN AND METHODS: A total of 636 nonpregnant women with diabetes (type 1 and type 2) who were 18-75 years of age and had no abnormalities of the urinary tract, and 153 women without diabetes who were visiting the eye and trauma outpatient clinic (control subjects) were included. We defined ASB as the presence of at least 10(5) colony-forming units/ml of 1 or 2 bacterial species in a culture of clean-voided midstream urine from an individual without symptoms of a urinary tract infection (UTI). RESULTS: The prevalence of ASB was 26% in the diabetic women and 6% in the control subjects (P < 0.001). The prevalence of ASB in women with type 1 diabetes was 21%. Risk factors for ASB in type 1 diabetic women included a longer duration of diabetes, peripheral neuropathy, and macroalbuminuria. The prevalence of ASB was 29% in women with type 2 diabetes. Risk factors for ASB in type 2 diabetic women included age, macroalbuminuria, a lower BMI, and a UTI during the previous year. No association was evident between current HbA1c level and the presence of ASB. CONCLUSIONS: The prevalence of ASB is increased in women with diabetes and might be added to the list of diabetic complications in these women.

Adult↗
PubMed2000

Procoagulant activity of endothelial cells after infection with respiratory viruses.

Influenza virus epidemics are associated with excess mortality due to cardiovascular diseases. There are several case reports of excessive coagulation during generalised influenza virus infection. In this study, we demonstrate the ability of respiratory viruses (influenza A, influenza B, parainfluenza-1, respiratory syncytial virus, adenovirus, cytomegalovirus) to infect lung fibroblasts and human umbilical vein endothelial cells in culture. All viral pathogens induced procoagulant activity in infected endothelial cells, as determined in a one-stage clotting assay, by causing an average 55% reduction in the clotting time. When factor VII deficient plasma was used clotting time was not reduced. The induction of procoagulant activity was associated with a 4- to 5-fold increase in the expression of tissue factor, as measured by the generation of factor Xa. Both experiments indicate that the procoagulant activity of endothelial cells in response to infection with respiratory viruses is caused by upregulation of the extrinsic pathway. Although both enveloped viruses and a non-enveloped virus (adenovirus) induced procoagulant activity in endothelial cells by stimulating tissue factor expression, the role of the viral envelope in the assembly of the prothrombinase complex remains uncertain. We conclude that both enveloped and non-enveloped respiratory viruses are capable of infecting cultured human endothelial cells and causing a shift from anticoagulant to procoagulant activity associated with the induction of tissue factor expression.

Blood Coagulation↗
PubMed1999

Interleukin-6 production by endothelial cells after infection with influenza virus and cytomegalovirus.

Inflammation plays a role in the pathogenesis of cardiovascular diseases. Viruses may be a cause of chronic inflammation, and both influenza virus and CMV have been associated with cardiovascular diseases. IL-6, a proinflammatory cytokine with antiviral effects, has a pivotal role in the immune response, and under pathologic conditions, prohemostatic effects of IL-6 could lead to pathologic thrombosis and vascular plaque instability. To investigate this role of IL-6, we measured the production of IL-6 by human endothelial cells after infection with influenza virus and CMV. After infection with influenza virus or CMV, IL-6 release into the medium increased (1756.5+/-156.9 pg/mL vs 284.4+/-55.3 pg/mL; P < .001) for influenza-Infected compared with uninfected cells after 36 hours' incubation. Ultracentrifuged influenza virus supernatants, heat-inactivated virus, and purified hemagglutinin were not able to elicit IL-6 synthesis by human endothelial cells. These findings show that CMV and influenza virus are capable of modulating the in vitro production of IL-6, a cytokine involved in vascular inflammation, by human endothelial cells.

Cells, Cultured↗
PubMed1998

[Factitious insulinoma].

A 32-year-old woman was admitted with signs of recurrent hypoglycaemia. Within 72 hours hypoglycaemia was successfully provoked by prolonged fasting. Also, blood samples demonstrated high levels of serum insulin and C-peptide and the insulin-glucose ratio was abnormally high. An insulinoma was strongly suspected. However, extensive imaging displayed no tumour in the pancreas. The patient also had extensive psychological and social problems. The psychiatrist suggested a factitious disorder. High serum concentrations of insulin and C-peptide in combination with the psychiatric disorder led to the suspicion of abuse of sulfonylurea derivatives by the patient. This was confirmed by toxicological screening. A patient with unexplained hypoglycaemia, especially if an insulinoma cannot be detected, should be suspected of abusing sulfonylurea derivatives.

Adult↗
PubMed1998

Tissue concentrations after a single-dose, orally administered ofloxacin in patients with diabetic foot infections.

We studied the penetration of orally administered ofloxacin at the site of diabetes-related foot infections in patients with a planned debridement of the lesion. A total of nine patients received 800 mg of oral ofloxacin 120 to 150 minutes before surgery. During surgery, vital margin tissue and a serum sample were obtained. Serum and tissue concentrations of ofloxacin were measured. From seven patients sufficient amounts of tissue were obtained. Mean serum concentration was 7.0+/-3.5 mg/liter; mean tissue concentrations was 11.5+/-8.4 mg/kg. Mean serum and tissue concentrations exceed the minimal inhibitory concentration90 (MIC90) of commonly involved pathogens. This indicates that orally administered ofloxacin can be an effective treatment for infected diabetic foot lesions.

Administration, Oral↗
PubMed1997

Patients with diabetes mellitus and atherosclerosis; a role for cytomegalovirus?

Diabetic patients are known to have an impaired immune response to viral antigens and a high incidence of atherosclerosis. This study was initiated to evaluate the association between cytomegalovirus infection and atherosclerosis in patients with diabetes mellitus. Patients with diabetes mellitus type 1 and 2 (> 5 years) with (group A) and without (group B) clinical signs of atherosclerosis were included. Cytomegalovirus cultures were obtained, serum was screened for CMV-antibodies and CMV-IgG and CMV-IgM titers were determined. Cytomegalovirus antibodies were detected more often in diabetic patients with atherosclerosis compared to patients without atherosclerosis (70.7 vs. 45.2%, P = 0.018. In female patients the prevalence of CMV-antibodies was 89.5 vs. 40.0% (P = 0.0037). CMV IgG titers were twice as high in group A compared to group B. Cytomegalovirus was cultured from four urine samples and two throat swabs in group B and in one urine and one throat swab in group A. The prevalence of cytomegalovirus antibodies was higher in diabetic patients with atherosclerosis compared to diabetic patients without atherosclerosis. This difference was most striking in the female population. CMV-IgG titers were twice as high in the atherosclerosis group. These data suggest that cytomegalovirus may play a role in the development of clinical atherosclerosis in patients with diabetes mellitus.

Antibodies, Viral↗
PubMed1994

[Large variation in the treatment of foot infections in diabetic patients in The Netherlands].

OBJECTIVE: To determine the treatment of foot infections in patients with diabetes mellitus and the implementation of the Dutch consensus guidelines. DESIGN: Questionnaire. SETTING: Nationwide. METHOD: To 180 internists and paediatricians were sent a letter explaining the objective of the survey and a questionnaire. After two months an identical questionnaire was sent, with the request to return it when the first questionnaire had not been returned yet. RESULTS: Seventy-three questionnaires (40%) were returned of which 63 were evaluable. The main reason for hospitalisation was the threat of limb loss (90%). Most patients presenting with superficial wound infections were treated with local surgical procedures (90%); however, 16% of the responders considered hospitalisation indicated. If osteomyelitis was present 81% of the responders would hospitalize the patient. Antibiotic treatment was instituted by 93%. In all, 11 different antibiotics were used. Of antibiotic combinations the combination of penicillin and lincomycin was used most frequently and the recommended combination of aminoglycoside and lincomycin least. The main reason for using a combination of antibiotics was presence of polymicrobial flora (93%). CONCLUSION: We conclude that treatment of diabetic foot is still very diverse in spite of the consensus guidelines.

Anti-Bacterial Agents↗
PubMed1993

The diabetic foot in Dutch hospitals: epidemiological features and clinical outcome.

OBJECTIVE: To assess the impact of the diabetic foot on the hospitalization of patients with diabetes mellitus in The Netherlands. METHODS: Data on hospitalizations of patients with diabetes mellitus for the years 1988 and 1989 were obtained from the Dutch Information System on Hospital Care. Analysis of the data was performed if in the discharge summary a code number for chronic ulcer of the lower extremity, osteomyelitis or gangrene was reported. RESULTS: In 1988 20.4% of all hospitalized diabetics were reported to have foot problems. The men age of the study population was 71.3 +/- 12.1 years for 1988 and 71.2 +/- 11.9 for 1989. In patients who underwent (partial) limb amputation the M/F ratio was higher than in patients without amputation for all patient groups studied (p < 0.001). In 1988, 3707 and in 1989, 3790 patients were hospitalized for diabetic foot problems. The cumulative costs were calculated to be 38,556,960 ECU for 1988 and 37,720,020 ECU for 1989. The mean duration of hospitalization was 40.0 days in 1988 and 38.3 days in 1989. Patients with limb amputation stayed significantly longer in the hospital than patients without amputation (p < 0.001). Overall in-hospital mortality was 10%. Mortality was highest in patients staged Wagner 4 + 5. Mortality among patients staged Wagner 1 and 2 was higher than in patients with osteomyelitis (p < 0.001). Of all patients, approximately 10% were discharged to a rehabilitation centre or nursing home. CONCLUSION: Both the mean age of the patients hospitalized and the total amount of costs involved are higher than put forward previously in studies from the US Diabetic foot problems put a heavy burden on the health status of elderly diabetic patients. Financial resources should be reallocated in the direction of preventive health care.

Aged↗
PubMed1992

Influence of blood glucose levels on peripheral lymphocytes in patients with diabetes mellitus.

Abnormalities in lymphocyte subpopulations in patients with type 1 diabetes have been reported previously. To evaluate the effect of blood glucose levels on peripheral lymphocyte concentrations we studied the proportion and phenotypic composition of the T-cell population in 7 patients with type 1 and in 12 patients with type 2 diabetes at hospitalization because of metabolic dysregulation and in a period of restored control. Both the number of CD-4 and CD-8 positive cells increased significantly (p < 0.05), although no change in the CD-4:CD-8 ratio was observed. After restoring metabolic control there was a significant rise in the mean number of total lymphocytes (1760 +/- 759 x 10(6)/ml vs 2385 +/- 889 x 10(6)/ml, p < 0.05). The number of total lymphocytes increased in all patients but one. It is concluded that metabolic control can influence immunological parameters such as numbers of peripheral lymphocytes of various phenotypes.

Adult↗
PubMed1991

A prospective study of in vitro anti-HBs producing B cells (spot-ELISA) following primary and supplementary vaccination with a recombinant hepatitis B vaccine in insulin dependent diabetic patients and matched controls.

A prospective study of the immune response after hepatitis B vaccination was carried out in 32 insulin dependent diabetes mellitus (IDDM) patients and their age and sex matched healthy controls. A sensitive, immunoenzymatic technique was used, able to detect in vitro specific antibody production by mitogen stimulated individual B cells. In-vivo serologic response after vaccination with a standard scheme (0, 1 and 6 months) of 20 micrograms recombinant hepatitis B (HB) vaccine was significantly impaired in the IDDM patients both with respect to the number of nonresponders (25 versus 3%, P less than 0.05) and antibody titers reached (1,377 vs. 9,060 IU/L, P less than 0.05). The total number of in vitro IgM- and IgG-class immunoglobulin producing B cells as detected by the spot-ELISA, was found to be comparable in both groups. Specific IgG anti-HBs (and to a lesser extent IgM anti-HBs) showed impairment in the diabetic population as a whole. The number of IgG anti-HBs producing B cells was markedly depressed one month following vaccination, which is probably a reflection of homing of B cells outside the circulation. Responding subjects were identified early during their vaccination by the detection of in vitro anti-HBs production using the spot-ELISA. Non-responding healthy subjects and IDDM patients as a group showed a low number of IgG anti-HBs spots, suggesting a reduced specific memory B cell frequency. In 13 of 15 hypo- and nonresponders with positive IgG anti-HBs spots supplementary vaccination(s) resulted in improved anti-HBs levels.

Adult↗