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Biomedical subjects

A Buchwald

Publications and source records attributed to A Buchwald.

At least 19 recordsLinked to original sources
PubMed2006

Inhaled insulin as adjunctive therapy in subjects with type 2 diabetes failing oral agents: a controlled proof-of-concept study.

AIM: This controlled proof-of-concept study investigated inhaled insulin (INH) as adjunctive therapy to existing oral antidiabetic agents in subjects with type 2 diabetes. METHODS: Twenty-four subjects with type 2 diabetes [19 men and 5 women, 56.1 +/- 6.6 years, body mass index 32.7 +/- 4.2 kg/m(2), glycosylated haemoglobin (HbA1c) 8.4 +/- 0.8% (mean +/- s.d.)] inadequately controlled by metformin and/or sulfonylureas were randomized to receive additional therapy with either INH administered preprandially using a metered-dose inhaler (MDI), or insulin glargine (GLA) injected subcutaneously at bedtime for 4 weeks. Both inhaled and injected insulin doses were titrated to predefined blood glucose (BG) targets. RESULTS: INH and GLA improved metabolic control to a similar extent. Mean daily BG decreased by 2.8 mmol/l in the INH group (p < 0.001) and by 2.4 mmol/l in the GLA group (p < 0.001). Accordingly, fasting BG (-2.7 vs. -3.6 mmol/l for INH vs. GLA), preprandial- and 2-h postprandial BG, HbA1c (-1.23 vs. -1.05%), body weight (-1.9 vs. -2.3 kg) and serum fructosamine were similarly and significantly reduced in both groups (p < 0.05). Triglycerides decreased significantly with INH (-1.15 micromol/l; p < 0.001) but not with GLA [-0.52 micromol/l; not significant (NS)]. Incidence rates of adverse events did not differ significantly, and there were no indications of respiratory tract irritation. CONCLUSIONS: In subjects with type 2 diabetes inadequately controlled by oral agents, preprandial administration of INH delivered by a MDI provided a comparable metabolic control to bedtime GLA and did not show any safety concerns during a 4-week treatment. These results warrant a more extensive investigation of preprandial treatment with INH in longer term studies.

Administration, Inhalation↗
PubMed2005

Fasting hyperglucagonemia in patients with transjugular intrahepatic portosystemic shunts (TIPS).

BACKGROUND: Hyperglucagonemia has been described to be associated with insulin resistance in patients with liver cirrhosis. Portosystemic shunts may be involved in the etiology of hyperglucagonemia. To test this hypothesis we investigated fasting peripheral plasma glucagon levels before and after portal decompression by transjugular intrahepatic portosystemic shunting (TIPS). METHODS: Glucagon, insulin, plasma glucose, HbA1c, and C-peptide were determined in peripheral venous samples from 21 non-diabetic (ND)- and 15 diabetic patients (D; 3 treated with insulin, 3 with sulfonylurea, 9 with diet alone) with liver cirrhosis, showing comparable clinical features (gender, age, BMI, creatinine, Child-Pugh-score, complications, and etiology of liver cirrhosis) before, 3 and 9 months after elective TIPS implantation. Insulin resistance was calculated as R (HOMA) according to the homeostasis model assessment (HOMA). RESULTS: Glucagon levels before TIPS were elevated in patients with diabetes compared to patients without diabetes (D: 145.4 +/- 52.1 pg/ml vs. ND: 97.3 +/- 49.8 pg/ml; p = 0.057). 3 and 9 months after TIPS implantation glucagon levels increased significantly in ND (188.9 +/- 80.3 pg/ml and 187.2 +/- 87.6 pg/ml) but not in D (169.6 +/- 62.4 pg/ml and 171.9 +/- 58.4 pg/ml). While plasma glucose, HbA1c, and C-peptide were significantly higher in D than in ND, they did not change significantly 3 and 9 months after TIPS implantation. Insulin was increased in D before TIPS (D: 31.6 +/- 15.9 mU/l vs. ND: 14.8 +/- 7.1 mU/l; p = 0.0001). 3 and 9 months after TIPS insulin significantly increased in ND (26.6 +/- 14.7 mU/l and 23.2 +/- 10.9 mU/l vs. 14.8 +/- 7.1 mU/l before TIPS) but not in D. In ND R (HOMA) also increased from 3.5 +/- 2 mU x mmol/l(2) to 5.7 +/- 3.3 mU x mmol/l(2) after 3 and 5.4 +/- 2.6 mU x mmol/l(2) after 9 months. BMI, liver and kidney function did not change with time. CONCLUSION: In non-diabetic cirrhotic patients TIPS implantation is followed by an increase of glucagon. However, this does not result in a worsening of glycemic control, probably because of a simultaneous increase of insulin.

Adult↗
PubMed2003

The single nucleotide polymorphism -1131T>C in the apolipoprotein A5 (APOA5) gene is associated with elevated triglycerides in patients with hyperlipidemia.

The -1131T>C polymorphism in the newly identified apolipoprotein A5 (APOA5) gene has been associated with elevated plasma triglycerides. We determined its incidence in 915 patients attending a lipid outpatient clinic. The frequency of the C allele was significantly higher in patients with triglycerides above the 90th percentile and patients with type III hyperlipidemia compared to those with hypercholesterolemia. The C allele was associated with increased plasma triglycerides and decreased plasma HDL cholesterol, conditions associated with an increased risk of coronary heart disease. The effects on plasma lipids were only observed in overweight (BMI>25) patients and were greater in patients who were also carriers of a least one epsilon4 allele in the APOE gene. Thus additional genetic and/or metabolic factors are required in order for the triglyceride raising and HDL lowering effect of the -1131T>C polymorphism in APOA5 to be expressed.

Alleles↗
PubMed2002

Soft cannabinoid analogues as potential anti-glaucoma agents.

Cannabinoids are able to reduce elevated intraocular pressure; however, their use in glaucoma treatment is not approved due to severe systemic side effects. New cannabinoid derivatives have been designed based on a retrometabolic/soft drug approach; they were expected to have local effect, but not systemic side effects. Lead compounds and soft analogues were prepared using Pechmann condensation. In agreement with the SAR hypothesis used for the present soft drug design, all the compounds that were successfully synthesized had IOP lowering effect, but the common metabolite of soft analogues that was found to be inactive. Accordingly, when the soft analogue 8 was administered i.v., its biological effect lasted just for 15 minutes; nevertheless, when administered topically, its effect lasted significantly longer. Its metabolite, though, was inactive when applied either i.v. or topically. Thus, the designed soft analogues proved to be good candidates for topical control of glaucoma without producing systemic side effects. The preliminary i.v. experimental data could be successfully described by an indirect response PK/PD model.

Administration, Topical↗
PubMed2001

Systemic bioavailability of nasally applied chlorphenamine maleate (0.4% nasal spray) relative to tablets administered perorally.

AIM: This study investigated the bioavailability of single doses of 1.12 and 2.24 mg chlorphenamine maleate applied intranasally (0.4% nasal spray) relative to a single peroral dose of 8 mg chlorphenamine maleate (tablets). METHODS: Twenty-four (24) subjects were treated with single nasal doses of 1.12 mg and 2.24 mg chlorphenamine maleate (0.4% nasal spray) and two 4 mg chlorphenamine maleate tablets (Piriton) on 3 separate study days according to a 3-way cross-over design with a 7-day wash-out between periods. Blood was sampled before and at 0.25, 0.50, 1.0, 2.0, 3.0, 4.0, 6.0, 8.0, 12, 16 and 24 hours after drug administration. Additional blood samples were obtained 36, 48 and 72 hours after peroral administration only. All subjects were included in the pharmacokinetic analysis. RESULTS: Nasally applied chlorphenamine maleate was readily absorbed, reaching peak plasma levels after 0.25 to 3.0 hours. The dose-normalized estimated mean Cmax values were 1.24, 1.43 and 1.21 ng/ml for the peroral tablet and the 1.12 mg and 2.24 mg nasal dose, respectively. The dose-normalized estimated mean AUC(0-infinity) values were 25.91, 26.44 and 25.56 ng x h/ml for the tablet and the 1.12 and 2.24 mg nasal dose, respectively. The estimated treatment ratios (nasal dose to tablet) of the dose-normalized values for the 1.12 mg nasal dose were 1.15 (900 CI: 1.0-1.32) and 1.02 (90% CI: 0.88-1.18) for Cmax and AUC(0-infinity), respectively, for the 2.24 mg nasal dose they were 0.98 (90% CI: 0.85-1.13) and 0.99 (90% CI: 0.85-1.13) for Cmax and AUC(0-infinity), respectively. The other pharmacokinetic characteristics (tmax, t(1/2), lambda(z), AUC(0-tf), MRTtot, CL/f and Vz/f) were comparable across all treatments. These data indicate that the disposition of chlorphenamine maleate was independent of the route and dose of administration. CONCLUSIONS: Chlorphenamine maleate is readily absorbed after nasal application using a 0.4% nasal spray. The nasal administration showed that the systemic bioavailability at the two dose levels used was comparable to that for the tablet. Maximum concentrations on the low dose, however, were higher and those on the high dose were comparable to those for the tablet. The nasal application of chlorphenamine maleate does not alter the overall systemic exposure compared to the oral route.

Administration, Intranasal↗
PubMed2000

Soft cannabinoid analogues as potential anti-glaucoma agents.

Cannabinoids have intraocular pressure (IOP) lowering effects, thus, they have a therapeutic potential in the treatment of glaucoma. Unfortunately, in the same time, they show CNS and cardiovascular effects as well. Our aim was to develop a safer, cannabinoid type anti-glaucoma agent, a topically applied soft analogue, that has local, but no systemic effect. The lead compound chosen was a nitrogen-containing cannabinoid analogue that was shown to have IOP lowering activity. A full library of possible soft drugs was generated and the structures were ranked based on the closeness of calculated properties to those of the lead compound. The lead compound has been synthesized, and a preliminary pharmacological study was performed. The structure-activity relationship and pharmacological results indicate a good possibility for the development of a safe, soft anti-glaucoma agent.

Animals↗
PubMed1999

Hypercoagulability in a patient with hypodysfibrinogenemia: implications for clinical management.

Dysfibrinogenemia accounts for approximately 0.7% of thrombophilia in patients with venous thromboembolic disease. In 20% of these patients, plasma thrombophilic dysfibrinogen is below 1.0 mg/ml, defining hypodysfibrinogenemia. We describe a young female patient, in whom hypodysfibrinogenemia was the cause of several severe thromboembolic events which occurred even under oral anticoagulation monitored by a standard prothrombin time (PT) test. In this patient, the standard PT test according to Quick underestimated the plasma coagulability in vivo, presumably due to the low levels of dysfunctional fibrinogen as the substrate of the thromboplastin reagent. A PT test supplemented with bovine plasma fibrinogen (Thrombotest) revealed lower fibrinogen-independent international normalized ratio (INR) values in the proposita on oral anticoagulation compared to a control group with eufibrinogenemia. Monitoring therapy with the fibrinogen-independent Thrombotest secured safe anticoagulation in this patient. We suggest to consider PT tests with exogenous fibrinogen (e.g. Thrombotest) to monitor oral anticoagulation in the rare thrombophilic patients with hypodysfibrinogenemia.

Adult↗
PubMed1998

Pharmacokinetic and pharmacodynamic aspects of salmeterol therapy.

BACKGROUND: Salmeterol xinafoate is a highly selective beta2-adrenoceptor for the maintenance treatment of asthma in adults and children. OBJECTIVE: To review the pharmacokinetics, clinical pharmacology, and therapeutic properties of a recently introduced, long acting antiasthmatic drug. METHODS: Recent English-language publications were selected using Medline as database. RESULTS: Salmeterol's pharmacokinetics, clinical pharmacology, and therapeutic properties are reviewed and aspects related to salmeterol's unusual duration of action, its high potency, beta2-selectivity, possible antiinflammatory actions, its interaction with other drugs, low systemic adverse effects, dosage, and administration are also discussed. CONCLUSION: Salmeterol is a safe long-acting beta2-agonist very useful for maintenance treatment of asthma.

Adrenergic beta-Agonists↗
PubMed1997

Recanalization of total coronary occlusions using a laser guidewire (the European TOTAL Surveillance Study).

The success rates of coronary angioplasty for the treatment of chronic total occlusions are less favorable than for coronary stenosis. Therefore, a new laser guidewire (LW) was designed to facilitate the crossing of chronic total occlusions. We report on the results of a European multicenter surveillance study, evaluating the laser guidewire performance. Between May 1994 and July 1996, 345 patients (age 59 +/- 10 years, 291 men) with chronic total occlusions were enrolled in 28 European centers. The median age of occlusion was 29 weeks (range 2 to 884), the occlusion length 19 +/- 10 mm. LW recanalization was successful in 205 patients (59%/). LW perforation occurred in 73 patients (21%), with hemodynamic consequences in 4 (1%). There were no deaths, emergency coronary artery bypass graft surgery, or Q-wave myocardial infarctions. In a multivariate regression analysis an occlusion age of <40 weeks (p = 0.001, RR = 1.34) and an occlusion length <30 mm (p = 0.01, RR = 1.59) were independent predictors of success. Results indicate that the LW is an effective and safe tool in the treatment of chronic total occlusion refractory to conventional guidewires.

Chronic Disease↗
PubMed1997

Fragmin in unstable angina pectoris or in non-Q-wave acute myocardial infarction (the FRIC study). Fragmin in Unstable Coronary Artery Disease.

The safety and efficacy of weight-adjusted, low-molecular-weight heparin (dalteparin) was compared with that of unfractionated heparin during 6 days of treatment in 1,482 patients with unstable angina or non-Q-wave myocardial infarction. Dalteparin, at a lower dose, was compared with placebo during the following 39 days. No significant outcome difference was found between the 2 treatment regimens in the unblinded phase (days 1-6). Between days 6-45 the rates of death, myocardial infarction, and recurrence of angina were comparable between the active treatment and placebo groups. The results suggest that twice-daily administration of subcutaneous dalteparin may be an effective and safe alternative to unfractionated heparin during the acute phase of unstable coronary artery disease. Prolonged treatment with dalteparin at a lower once-daily dose did not confer any additional benefit over aspirin (75-165 mg) alone.

Angina, Unstable↗
PubMed1997

Comparison of low-molecular-weight heparin with unfractionated heparin acutely and with placebo for 6 weeks in the management of unstable coronary artery disease. Fragmin in unstable coronary artery disease study (FRIC)

BACKGROUND: Low-molecular-weight heparin has a number of pharmacological and pharmacokinetic advantages over unfractionated heparin that make it potentially suitable, when used in combination with aspirin, for the treatment of unstable coronary artery disease. METHOD AND RESULTS: Patients with unstable angina or non-Q-wave myocardial infarction (1482) were included in the study, which had two phases. In an open, acute phase (days 1 to 6), patients were assigned either twice-daily weight-adjusted subcutaneous injections of dalteparin (120 i.u./kg) or dose-adjusted intravenous infusion of unfractionated heparin. In the double-blind, prolonged treatment phase (days 6 to 45), patients received subcutaneously either dalteparin (7500 i.u. once daily) or placebo. During the first 6 days, the rate of death, myocardial infarction, or recurrence of angina was 7.6% in the unfractionated heparin-treated patients and 9.3% in the dalteparin-treated patients (relative risk, 1.18; 95% confidence interval [CI], 0.84 to 1.66). The corresponding rates in the two treatment groups for the composite end point of death or myocardial infarction were 3.6% and 3.9%, respectively (relative risk, 1.07; 95% CI, 0.63 to 1.80). Revascularization procedures were undertaken in 5.3% and 4.8% of patients in unfractionated heparin and dalteparin groups, respectively (relative risk, 0.88; 95% CI, 0.57 to 1.35). Between days 6 and 45, the rate of death, myocardial infarction, or recurrence of angina was 12.3% in both the placebo and dalteparin groups (relative risk, 1.01; 95% CI, 0.74 to 1.38). The corresponding rates for death or myocardial infarction were 4.7% and 4.3% (relative risk, 0.92; 95% CI, 0.54 to 1.57). Revascularization procedures were undertaken in 14.2% and 14.3% of patients in the placebo and dalteparin groups, respectively. CONCLUSIONS: Our results add to previous evidence suggesting that the low-molecular-weight heparin dalteparin administered by twice-daily subcutaneous injection may be an alternative to unfractionated heparin in the acute treatment of unstable angina or non-Q-wave myocardial infarction. Prolonged treatment with dalteparin at a lower once-daily dose in our study did not confer any additional benefit over aspirin (75 to 165 mg) alone.

Adult↗
PubMed1993

Stent wire cutting during coronary directional atherectomy.

Directional atherectomy represents one potential approach for the treatment of restenosis in stented coronary arteries. In this case report we demonstrate an important pitfall of this angioplasty technique for stent restenosis--inadvertent entanglement of the stent wire in the device. While cutting and removal of part of the wire was achieved in the case presented, this potential adverse event limits the applicability of directional atherectomy for restenosis in coronary stents.

Angioplasty, Balloon, Coronary↗
PubMed1992

Coronary angioplasty in patients with previous coronary artery bypass grafting.

Between 1982 and 1990, in 134 patients with prior coronary artery bypass grafting and recurrent angina, repeat coronary angiography and balloon angioplasty of stenoses in grafts or native arteries were attempted. Mean age of grafts was 45.6 months, range three days to twelve years. At the time of angioplasty, 6 patients had one-vessel-disease, 33 had two-vessel-disease, and 95 had three-vessel-disease. A total of 182 lesions were dilated: 55 venous grafts, 3 internal mammary artery grafts, and 124 native vessels. Forty-nine of 55 (89%) venous grafts could be successfully dilated, and in 3 internal mammary artery grafts, a stenosis reduction greater than 50% was achieved. In 65 of 88 (74%) grafted native arteries, dilation success was achieved. Twenty-seven of 36 (75%) patients with prior bypass surgery to other arteries had successful angioplasty of nongrafted native arteries. Three patients underwent emergency bypass surgery after dissection and acute occlusion: one of them died in cardiogenic shock secondary to acute myocardial infarction. The angiographic success rate in grafts was slightly higher than in native arteries (90% vs 74%). These data indicate that percutaneous transluminal coronary angioplasty in patients after bypass surgery is possible at a low risk (3%) and constitutes an effective therapy in symptomatic patients.

Aged↗
PubMed1991

[Intravascular sonography of the coronary vessels following percutaneous transluminal angioplasty].

Intravascular ultrasound imaging was performed in 15 patients (three women and 12 men; mean age 55 [48-70] years) after percutaneous balloon angioplasty of the right coronary artery (7 patients), the anterior interventricular branch (6) or the circumflex branch of the left coronary artery (2). The catheter, external diameter 4.8 F, was advanced over a 0.014--in coronary wire to the area of the previously balloon-dilated stenosis. Vessel diameter measured by ultrasound correlated closely with that by angiography (r = 0.93; P less than 0.001). Ultrasound imaging distinguished between concentric and eccentric intimal thickening and made it possible to assess the consistency and degree of calcification of the wall changes. The success of angioplasty was evaluated in 10 patients. In eight, local dissection was revealed, but only three of them had been diagnosed angiographically. In one patient a vessel spasm was recorded during ultrasound imaging; it regressed after the intracoronary injection of 0.2 mg nitroglycerin. There were no other complications. The method made it possible to assess in vivo the extent and consistency of atherosclerotic plaques, and it adds to the angiographic monitoring of treatment results and of complications after angioplasty.

Aged↗
PubMed1991

Initial clinical results with the Wiktor stent: a new balloon-expandable coronary stent.

The Wiktor stent, a new coronary balloon-expandable tantalum stent, was implanted in 17 patients for other wise nonmanageable occlusion after balloon angioplasty (n = 11) and for recurrent restenosis (n = 6). Stents of 3.0 to 4.0 mm were implanted (right coronary artery: n = 10, left anterior descending artery: n = 4, left circumflex artery: n = 2, venous graft: n = 1). All patients were fully anticoagulated initially with heparin followed by coumadin for 3 months and were treated with acetylsalicylic acid indefinitely. Due to its good radiopacity, the device could be placed easily without complications. Early occlusion occurred in one patient after 8 h probably due to friable atheromatous material prolapsing between the meshes of the stent. Late occlusion occurred in another patient who was admitted in cardiogenic shock after pre-hospital reanimation and was stented after occlusive disection following balloon angioplasty of an occluded right coronary artery. In this patient with severe hypoxic brain damage, reocclusion and reinfarction to which the patient finally succumbed occurred following cessation of anticoagulation. Histology demonstrated occlusive thrombosis without evidence of a neointimal covering of the stent. Another thrombotic occlusion due to inadvertent omission of anticoagulation occurred in another patient two weeks after stenting. Control angiography after 6 months in 12 patients revealed restenosis in two patients (50% and 80%). The patient with 80% restenosis of the right coronary artery and pathologic results during stress testing underwent surgical revascularization. The other patient with a 50% restenosis of the right coronary artery was managed medically as he was asymptomatic and without evidence of ischemia during stress testing.(ABSTRACT TRUNCATED AT 250 WORDS)

Angioplasty, Balloon, Coronary↗