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Biomedical subjects

A Kooy

Publications and source records attributed to A Kooy.

17 recordsLinked to original sources
PubMed2005

Effects of short-term treatment with metformin on markers of endothelial function and inflammatory activity in type 2 diabetes mellitus: a randomized, placebo-controlled trial.

OBJECTIVES: The UK Prospective Diabetes Study (UKPDS) showed that treatment with metformin decreases macrovascular morbidity and mortality independent of glycaemic control. We hypothesized that metformin may achieve this by improving endothelial function and chronic, low-grade inflammation. Data on this issue are scarce and we therefore tested, in the setting of a randomized, placebo-controlled trial, whether metformin can affect endothelial function and low-grade inflammation. DESIGN: The Hyperinsulinaemia the Outcome of its Metabolic Effects (HOME) trial is a double-blind trial, in which all patients were randomized to receive either metformin or placebo in addition to insulin therapy. At the beginning and the end of a 16-week treatment period fasting blood samples were drawn and a physical examination was carried out. SETTING: The trial was conducted in the outpatient clinics of three nonacademic hospitals (Hoogeveen, Meppel and Coevorden; the Netherlands). SUBJECTS: Patients were included if they were between 30 and 80 years of age; had received a diagnosis of diabetes after the age of 25; had never had an episode of ketoacidosis; and their blood glucose-lowering treatment previously consisted of oral agents but now only consisted of either insulin (n = 345) or insulin and metformin (n = 45). We excluded pregnant women and women trying to become pregnant, patients with a Cockroft-Gault-estimated creatinine clearance <50 mL min(-1), or low plasma cholinesterase (reference value <3.5 units L(-1)), patients with congestive heart failure (New York Heart Association class III/IV), or patients with other serious medical or psychiatric disease. A total of 745 eligible patients were approached; 390 gave informed consent and were randomized (196 metformin, 194 placebo). About 353 patients completed 16 weeks of treatment (171 metformin, 182 placebo). MAIN OUTCOME MEASURES: The HOME trial was designed to study the metabolic and cardiovascular effects of metformin during a follow-up of 4 years. Presented here are the results of an interim analysis after 16 weeks of treatment. RESULTS: When compared with placebo, metformin treatment was associated with an increase in urinary albumin excretion of 21% (-1 to +48; P = 0.06); a decrease in plasma von Willebrand factor of 6% (-10 to -2; P = 0.0007); a decrease in soluble vascular cell adhesion molecule-1 of 4% (-7 to -2; P = 0.0002); a decrease in soluble E-selectin of 6% (-10 to -2; P = 0.008); a decrease in tissue-type plasminogen activator of 16% (-20 to -12; P < 0.0001); and a decrease in plasminogen activator inhibitor-1 of 20% (-27 to -10; P = 0.0001). These changes could not be explained by metformin-associated changes in glycaemic control, body weight or insulin dose. Markers of inflammation, i.e. C-reactive protein and soluble intercellular adhesion molecule-1, did not change with metformin treatment. CONCLUSIONS: In patients with type 2 diabetes treated with insulin, metformin treatment was associated with improvement of endothelial function, which was largely unrelated to changes in glycaemic control, but not with improvement of chronic, low-grade inflammation.

Adult↗
PubMed2005

Does metformin decrease blood pressure in patients with Type 2 diabetes intensively treated with insulin?

AIMS: We investigated in a double-blind study whether metformin reduces blood pressure (BP) in patients with Type 2 diabetes intensively treated with insulin. METHODS: A total of 220 patients with Type 2 diabetes were asked to undergo 24-h ambulatory BP monitoring (24-h ABPM). One hundred and eighty-two gave informed consent. Eighty-nine were randomized to metformin and 93 to placebo. Thirty-five subjects dropped out (13 placebo, 22 metformin users); 147 patients underwent a second 24-h ABPM, 16 weeks after randomization. RESULTS: Systolic BP (SBP), diastolic BP (DBP), pulse BP (PP), mean BP (MP) and heart rate (HR) were measured as office BP measurements and as 24-h ABPM for 24-h, day and night. Office BP measurements did not differ significantly between the placebo- and metformin-treated groups for any BP measure, but showed a non-significant trend for SBP reduction with metformin use (mean baseline-adjusted difference, metformin minus placebo: -4.2 mmHg, 95% CI, -9.9 to +1.5; P = 0.15). The baseline-adjusted differences of the ambulatory measurements were -0.2 mmHg (95% CI, -2.9 to +2.6) for the 24-h SBP, and +1.1 mmHg (95% CI, -0.7 to +2.8) for the 24-h DBP. On the whole, BP differences between metformin- and placebo-treated groups were not statistically significant. The only significant difference was for night-time PP (baseline-adjusted difference: -2.2 mmHg; 95% CI, -4.2 to -0.2). These results were not different after adjustment for age and diabetes duration, or for (changes in) body mass index, glycated haemoglobin, insulin dose or plasma homocysteine. CONCLUSION: Metformin does not significantly affect BP in patients with Type 2 diabetes intensively treated with insulin.

Age Factors↗
PubMed2004

The effect of metformin on blood pressure, plasma cholesterol and triglycerides in type 2 diabetes mellitus: a systematic review.

BACKGROUND: The UKPDS 34 showed that intensive treatment with metformin significantly reduces macrovascular end-points and mortality in individuals with newly diagnosed type 2 diabetes compared with intensive treatment with insulin or sulphonylurea derivatives, despite similar glycaemic control. How this should be explained is as yet unclear. We hypothesized that metformin may have a glucose-lowering independent effect on blood pressure and lipid profile. In order to test this hypothesis we systematically reviewed the literature and pooled the data obtained in a meta-analysis. METHODS: Included were randomized-controlled trials in patients with type 2 diabetes mellitus and metformin treatment lasting at least 6 weeks. To identify all eligible trials we conducted electronic searches using the bibliographic databases Medline and Embase, contacted the manufacturer and checked obtained publications for cross-references. RESULTS: Forty-one studies (3074 patients) provided data on blood pressure and/or lipid profile. When compared with control treatment, metformin associated effects on systolic and diastolic blood pressure and HDL cholesterol were small and statistically not significant [-1.09 mmHg 95% confidence interval (-3.01-0.82), P = 0.30; -0.97 (-2.15-0.21) mmHg, P = 0.11 and +0.01 (-0.02-0.03) mmol L(-1), P = 0.50, respectively]. Compared with control treatment, however, metformin decreased plasma triglycerides, total cholesterol and LDL cholesterol significantly [-0.13 (-0.21--0.04) mmol L(-1), P = 0.003; -0.26 (-0.34--0.18) mmol L(-1), P < 0.0001 and -0.22 (-0.31--0.13) mmol L(-1), P < 0.00001, respectively]. We found no indications for publication bias. Of note, glycaemic control as assessed by HbA1c was better with metformin than with control treatment [-0.74 (-0.84--0.65) percentage point; P < 0.00001]. When studies were subdivided into tertiles according to increasing difference in glycaemic control between metformin and control treatment, it appeared that in case of near similar glycaemic control metformin had no effect versus control treatment on triglycerides, whereas still there was a significant effect on total and LDL cholesterol. CONCLUSIONS: This meta-analysis of randomized-controlled clinical trials suggests that metformin has no intrinsic effect on blood pressure, HDL cholesterol and triglycerides in patients with type 2 diabetes. This drug, however, independent of its effect on glycaemia, reduces total and LDL cholesterol significantly, but the reductions in these variables are relatively small.

Blood Pressure↗
PubMed2003

Effects of short-term treatment with metformin on serum concentrations of homocysteine, folate and vitamin B12 in type 2 diabetes mellitus: a randomized, placebo-controlled trial.

OBJECTIVE: Metformin is a key treatment option in type 2 diabetes. However, metformin may decrease vitamin B12 levels and increase levels of homocysteine, a cardiovascular risk factor. We investigated whether 16 weeks of treatment with metformin affects serum concentrations of homocysteine, folate and vitamin B12 in subjects with type 2 diabetes treated with insulin. DESIGN: Placebo-controlled, randomized trial. MEASUREMENTS: at baseline and 16 weeks later. SETTING: This trial was conducted in the outpatient clinics of three general hospitals in The Netherlands. SUBJECTS: A total of 745 patients with type 2 diabetes, treated with insulin and not known with a contraindication for the use of metformin, were approached; 390 gave informed consent and entered the study. Thirty-seven subjects dropped out (12 placebo and 25 metformin users). INTERVENTION: Addition of metformin or placebo to insulin therapy. PRIMARY OUTCOME PARAMETERS: Serum homocysteine, folate, vitamin B12, indices of glycaemic control and body weight. RESULTS: Amongst those who completed 16 weeks of treatment, metformin use, as compared with placebo, was associated with an increase in homocysteine of 4% (0.2 to 8; P=0.039) and with decreases in folate [-7% (-1.4 to -13); P=0.024] and vitamin B12 [-14% (-4.2 to -24); P<0.0001]. In addition, the increase in homocysteine could be explained by the decreases in folate and vitamin B12. CONCLUSION: In patients with type 2 diabetes, 16 weeks of treatment with metformin reduces levels of folate and vitamin B12, which results in a modest increase in homocysteine. The clinical significance of these findings remains to be investigated.

Adult↗
PubMed2002

Discontinuation of metformin in type 2 diabetes patients treated with insulin.

BACKGROUND: Metformin added to insulin therapy in type 2 diabetic patients improves glycaemic control and decreases the required daily dose of insulin (DDI). Metformin should be discontinued if cardiac, hepatic or renal failure develops. We examined whether glycaemic control can be maintained after metformin cessation. METHODS: We included 45 type 2 diabetic patients treated with insulin plus metformin, and 45 matched controls treated with insulin only. After discontinuation of metformin in the first group, we aimed for tight fasting and postprandial blood glucose levels, 4-7 and 4-10 mmol/l, respectively, in both groups. During 12 weeks we assessed glycaemic control every two weeks and, if necessary, adjusted the insulin dosage. RESULTS: In the group in which metformin was discontinued, DDI increased from 67.9 +/- 22.9 to 92.2 +/- 29.4 IU (p < 0.001) leaving glycaemic control unchanged. In the controls, glycated haemoglobin (GHb) decreased by 0.93% (p < 0.001), while DDI increased slightly from 62.4 +/- 22.9 to 72.3 +/- 27.3 IU (p < 0.001). The increase in DDI was larger in patients in whom metformin was discontinued than in the controls (p < 0.001). CONCLUSIONS: In type 2 diabetic patients treated with insulin plus metformin, glycaemic control can be maintained after discontinuation of metformin by increasing the DDI substantially (20 to 36%) during application of an intensified treatment protocol.

Blood Glucose↗
PubMed1999

The influence of metronidazole resistance on the efficacy of ranitidine bismuth citrate triple therapy regimens for Helicobacter pylori infection.

AIM: To assess the influence of metronidazole resistance on the efficacy of ranitidine bismuth citrate-based triple therapy regimens in two consecutive studies. METHODS: In the first study, patients with a culture-proven Helicobacter pylori infection were treated with ranitidine bismuth citrate 400 mg, metronidazole 500 mg, and clarithromycin 500 mg, all twice daily for 1 week (RMC). In the second study, amoxycillin 1000 mg was substituted for clarithromycin (RMA). Susceptibility testing for metronidazole was performed with the E-test. Follow-up endoscopy was performed after >/= 4 weeks. Antral biopsy samples were taken for histology and urease test, and culture and corpus samples for histology and culture. RESULTS: 112 patients, 53 males, age 55 +/- 14 years (39 duodenal ulcer, 7 gastric ulcer and 66 gastritis) were treated with RMC, and 89 patients, 52 males, age 58 +/- 15 years (23 duodenal ulcer, 7 gastric ulcer and 59 gastritis) were treated with RMA. For RMC, intention-to-treat eradication results were 98% (59/60, 95% CI: 91-100%) and 95% (20/21, 95% CI: 76-100%) for metronidazole susceptible and resistant strains, respectively (P = 0.45). For RMA these figures were 87% (53/61, 95% CI: 76-94%) for metronidazole susceptible strains and 22% (2/9, 95% CI: 3-60%) for resistant strains (P = 0.0001). CONCLUSION: Both regimens are effective in metronidazole susceptible strains. However, in contrast to the amoxycillin-containing regimen, that containing clarithromycin is also effective in resistant strains.

Adult↗
PubMed1998

One-week triple therapy with ranitidine bismuth citrate, clarithromycin and metronidazole versus two-week dual therapy with ranitidine bismuth citrate and clarithromycin for Helicobacter pylori infection: a randomized, clinical trial.

OBJECTIVE: The aim of this study was to compare the efficacy and side effects of 1-wk triple therapy with ranitidine bismuth citrate (RBC) 400 mg b.i.d., clarithromycin 500 mg b.i.d., and metronidazole 500 mg b.i.d., to 2-wk dual therapy with RBC 400 mg b.i.d. and clarithromycin 500 mg b.i.d. for H. pylori infection in a randomized, clinical trial. METHODS: Patients (18-80 yr) with a culture proven H. pylori infection were randomized to one of these regimens. Side effects were scored on a semiquantitative scale. Endoscopy was performed > or = 4 wk after treatment. Antral biopsy samples were taken for hematoxylin-eosin stain (HE), rapid urease test, and culture and corpus samples for culture and HE. Two weeks after the endoscopy, a 13C-urea breath test was performed. Eradication failure was defined as detection of H. pylori by culture or by at least two other tests. RESULTS: A total of 104 patients, 54 men, age 54+/-14 yr, (36 duodenal ulcer, 16 gastric ulcer, and 52 functional dyspepsia) were included. Gender, age, and diagnosis were comparable in both groups. Fourteen of 52 patients in both triple and dual therapy, respectively, had significant side effects, but all patients completed the course. Eradication results were 49 of 52 (94%; 95% CI: 84-99%) and 50 of 52 (96%; 95% CI: 87-100%) on intention to treat analysis and 44 of 46 (96%; 95% CI: 85-99%) and 48 of 49 (98%; 95% CI: 89-100%) on per protocol analysis for triple and dual therapy respectively. CONCLUSION: Both regimens are very effective and well tolerated in the treatment of H. pylori infection. The triple regimen has the advantage of being shorter.

Adolescent↗
PubMed1997

Low cure rate of Helicobacter pylori infection with omeprazole and furazolidone dual therapy for one week.

BACKGROUND: Furazolidone is an inexpensive antibiotic that has considerable anti-Helicobacter pylori activity in vitro. METHODS: Twenty-three patients with culture-proven H. pylori infection were treated for one week with a dual therapy containing omeprazole and furazolidone. RESULTS: Eradication succeeded in 10 of the first 20 evaluable patients (50%; 95% CI: 27.2-72.8%). This percentage was regarded as too low, and the study was terminated. Side-effects were mild. CONCLUSION: With the possible increase in resistance to metronidazole and clarithromycin world-wide, furazolidone may be useful alternative in the treatment of H. pylori infection. Dual therapy for one week, however, is not sufficient.

Anti-Bacterial Agents↗
PubMed1997

One-week triple therapy with omeprazole, amoxycillin and tinidazole for Helicobacter pylori infection: the significance of imidazole resistance.

BACKGROUND: Triple therapy involving a proton pump inhibitor and two antibiotics has been suggested as an effective treatment for Helicobacter pylori infection. The impact of imidazole resistance on the efficacy of such regimens is largely unknown. METHODS: One hundred patients with culture proven H. pylori infection were treated with omeprazole 40 mg b.d., amoxycillin 1000 mg b.d., and tinidazole 500 mg b.d. for one week. Pre-treatment imidazole susceptibility was measured by disk diffusion. Resistance was confirmed by E-test. Eradication was assessed by endoscopy 6-8 weeks after the end of treatment. In cases of doubt a 13C-urea breath test was performed. Side-effects were scored using a semiquantitative scale. RESULTS: H. pylori was eradicated in 95% of the patients with an imidazole-susceptible strain and in 69% of the patients with a resistant strain (P < 0.005). Significant side-effects were seen in 12%. CONCLUSION: This proton pump inhibitor triple therapy is a simple, reasonably effective regimen with few significant side-effects. The efficacy is dependent on the susceptibility of the infecting H. pylori strain.

Aged↗
PubMed1996

Hepatitis in a patient with SLE: is it autoimmune hepatitis?

In a patient with systemic lupus erythematosus (SLE), we considered the diagnosis of autoimmune hepatitis (AIH) in view of raised serum aminotransferases, hypergammaglobulinaemia, antinuclear antibodies (titre 1:10,240), seronegativity of markers for viral hepatitis and absence of recent hepatotoxic drug usage. The diagnosis of AIH was supported by using the scoring system, recently developed by the International Autoimmune Hepatitis Group and the excellent response to treatment with prednisone. Liver histology, however, showed no characteristic features of AIH. The relevance of liver histology and scoring for AIH in SLE with hepatic involvement is discussed.

Adult↗
PubMed1996

Vertebral bone destruction in sickle cell disease: infection, infarction or both.

Infectious and vaso-occlusive vertebral bone and joint destruction in two patients with sickle cell disease (SCD) are featured by H-shaped vertebrae, kyphotic angulation, osteolysis of endplates and collapse of intervertebral discs as shown by X-ray films and magnetic resonance imaging. Staphylococcal serology supported the diagnosis of staphylococcal osteomyelitis/spondylo-discitis in both SCD patients. The difficulties of establishing the causes and treatment of the osteoarthropathy in these particular cases are discussed in the light of the literature.

Adult↗
PubMed1990

Evidence for the involvement of corticotropin-releasing factor in the inhibition of gonadotropin release induced by hyperprolactinemia.

The hypothesis was tested that corticotropin-releasing factor (CRF) is involved in the inhibition of gonadotropin secretion during chronic hyperprolactinemia. Two models of hyperprolactinemia were used, namely inoculation with the prolactin (PRL)-secreting tumor 7315b and implantation of isogenic pituitary glands. Gonadectomized, adrenalectomized male rats received a testosterone capsule and a corticosterone pellet and were inoculated subcutaneously with tumor 7315b. Similar rats without tumor served as controls. The rats were studied 3-4 weeks later while anesthetized with urethane. Plasma testosterone and corticosterone were similar in the two groups of rats. Compared to controls, the tumor-bearing rats had significantly higher plasma levels of PRL (100-fold increase) and adrenocorticotropin (ACTH; 3-fold increase), whereas plasma luteinizing hormone (LH) and follicle-stimulating hormone (FSH) had significantly decreased to 15 and 40%, respectively. CRF release into hypophysial stalk plasma was higher in rats with tumor 7315b than in controls (298 +/- 23 vs. 197 +/- 28 pg/h), and hypothalamic CRF content had increased from 3.0 +/- 0.3 to 4.3 +/- 0.3 ng. Male rats received 3 pituitary glands under the kidney capsule. Sham-operated rats served as controls. They were studied 5-7 weeks later while anesthetized with urethane. Compared to controls, pituitary-grafted rats had larger adrenals (49 +/- 4 vs. 34 +/- 2 mg), higher plasma PRL (156 +/- 18 vs. 52 +/- 8 ng/ml), ACTH (0.46 +/- 0.05 vs. 0.22 +/- 0.02 ng/ml) and corticosterone (455 +/- 39 vs. 268 +/- 14 ng/ml), and lower plasma levels of LH (21 +/- 2 vs. 41 +/- 6 ng/ml).(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenalectomy↗
PubMed1989

Effects of the new prolactin-producing tumour 7315b on gonadotrophin secretion in adult male and female rats.

The effects of the transplantable purely prolactin-secreting tumour 7315b on serum gonadotrophins were studied in adult rats. Possible contributions of the adrenals to the tumour-induced inhibition of serum LH and FSH were evaluated. The suppressive actions of tumour 7315b on serum gonadotrophins in gonadectomized plus adrenalectomized male and female rats were compared. Within 4 weeks after inoculation of tumour 7315b in intact male rats very high levels of prolactin and decreased serum levels of gonadotrophins and testosterone were recorded. At autopsy reduced weights of testes and accessory sex organs and slightly increased adrenal weights were found. In addition, in animals treated with a small testosterone-filled capsule after castration, tumour 7315b reduced serum concentrations of LH and FSH. Adrenalectomy did not prevent this suppressive action of the tumour on the post-castration rise of serum gonadotrophins. Suppression of serum gonadotrophins during hyperprolactinaemia was greater in gonadectomized plus adrenalectomized female rats than in male rats, indicating that the degree of the tumour-induced suppression of LH and FSH after castration is determined to a large extent by the sex of the animal. The purely prolactin-secreting tumour 7315b has therefore been shown to be a suitable model for studying the effects of severe hyperprolactinaemia on the pituitary-gonadal axis in rats.

Adrenalectomy↗
PubMed1988

Deterioration of male sexual behavior in rats by the new prolactin-secreting tumor 7315b.

The effects of hyperprolactinemia on male copulatory behavior in adult male and female rats were studied. Hyperprolactinemia was induced by the transplantable purely prolactin-secreting tumor 7315b. Male rats were castrated and received testosterone-filled capsules of different sizes which induced normal and subnormal testosterone levels. After sexual training the rats of the experimental groups were inoculated with tumor 7315b. Three weeks after tumor-inoculation high prolactin levels (2000-30000 ng/ml) were found. During this hyperprolactinemia ejaculation latency increased significantly, while the mount frequency and intromission frequency remained unchanged. Only 9 out of 22 rats ejaculated 19 days after inoculation. Moreover, it appeared that the inhibitory effect of the tumor was as strong in the presence of normal (2.33 +/- 0.07 ng/ml) as in the presence of low (0.35 +/- 0.01 ng/ml) testosterone levels. The inhibitory effect of tumor 7315b on copulatory behavior was not influenced by adrenalectomy. In gonadectomized female rats bearing testosterone-filled capsules tumor 7315b induced prolactin levels of about 2000 ng/ml and an almost complete cessation of mounts and intromission patterns 4 weeks after tumor-inoculation. It was concluded that tumor 7315b causes a strong inhibitory effect on male copulatory behavior in male and female rats and that this effect is not influenced by the presence of normal or low testosterone levels or removal of the adrenals, suggesting a direct effect of prolactin on brain functions.

Animals↗