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Biomedical subjects

M Zander

Publications and source records attributed to M Zander.

At least 19 recordsLinked to original sources

The metabolite generated by dipeptidyl-peptidase 4 metabolism of glucagon-like peptide-1 has no influence on plasma glucose levels in patients with type 2 diabetes.

AIM/HYPOTHESIS: Glucagon-like peptide-1 (GLP-1) is metabolised by the enzyme dipeptidyl-peptidase 4 (DPP-4), generating a metabolite with potential antagonistic properties. This study was conducted to evaluate the effect of that metabolite on plasma glucose levels in patients with type 2 diabetes. MATERIALS AND METHODS: The randomised crossover study consisted of five regimens: (1) i.v. infusion of GLP-1 (1.2 pmol kg(-1) min(-1); IV); (2 and 3) s.c. infusion of GLP-1 (2.4 and 9.6 pmol kg(-1) min(-1); LSC, HSC); (4) s.c. infusion of GLP-1 (2.4 pmol kg(-1) min(-1)) in combination with a DPP-4 inhibitor (IB); and (5) s.c. infusion of saline (154 mmol NaCl/l; SAL). Seven patients with type 2 diabetes participated in all protocols. RESULTS: Plasma levels of intact GLP-1 increased from 7+/-1 (SAL) to 17+/-3 (LSC), 61+/-7 (IB), 62+/-5 (IV) and 94+/-10 (9.6 s.c.) pmol/l, p<0.0001. Plasma concentrations of the metabolite increased from 1+/-3 (SAL) and 2+/-6 (IB) pmol/l to 42+/-4 (LSC), 64+/-8 (IV) and 327+/-16 (HSC) pmol/l, p<0.0001. Mean plasma glucose levels at 6 h decreased from 12.4+/-1.1 (SAL) mmol/l to 10.4+/-1.1 (LSC), 8.6+/-0.6 (IB), 8.8+/-0.8 (IV) and 9.1+/-0.9 (HSC) mmol/l, p<0.0001. CONCLUSIONS/INTERPRETATION: At approximately similar concentrations of intact GLP-1 (IV, IB, HSC), but with widely ranging metabolite concentrations, the effect on plasma glucose levels was equal, indicating that the presence of the metabolite does not antagonise the glucose-lowering effect of GLP-1.

Blood Glucose↗

Additive glucose-lowering effects of glucagon-like peptide-1 and metformin in type 2 diabetes.

OBJECTIVE: The incretin hormone glucagon-like peptide-1 (GLP-1) reduces plasma glucose in type 2 diabetic patients by stimulating insulin secretion and inhibiting glucagon secretion. The biguanide metformin is believed to lower plasma glucose without affecting insulin secretion. We conducted this study to investigate the effect of a combination therapy with GLP-1 and metformin, which could theoretically be additive, in type 2 diabetic patients. RESEARCH DESIGN AND METHODS: In a semiblinded randomized crossover study, seven patients received treatment with metformin (1,500 mg daily orally) alternating with GLP-1 (continuous subcutaneous infusion of 2.4 pmol x kg(-1) x min(-1)) alternating with a combination of metformin and GLP-1 for 48 h. Under fixed energy intake, we examined the effects on plasma glucose, insulin, C-peptide, glucagon, and appetite. RESULTS: Fasting plasma glucose (day 2) decreased from 13.9 +/- 1 (no treatment) to 11.2 +/- 0.4 (metformin) and 11.5 +/- 0.5 (GLP-1) and further decreased to 9.4 +/- 0.7 (combination therapy) (P = 0.0005, no difference between monotherapy with GLP-1 and metformin). The 24-h mean plasma glucose (day 2) decreased from 11.8 +/- 0.5 (metformin) and 11.7 +/- 0.8 (GLP-1) to 9.8 +/- 0.5 (combination) (P = 0.02, no difference between GLP-1 and metformin). Insulin levels were similar between the three regimens, but glucagon levels were significantly reduced with GLP-1 compared with metformin (P = 0.0003). Combination therapy had no additional effect on appetite scores. CONCLUSIONS: Monotherapy with GLP-1 and metformin have equal effects on plasma glucose and additive effects upon combination.

Blood Glucose↗

[Tricuspid valve endocarditis. Demonstration of a rare disease exemplified with 3 case reports].

BACKGROUND: Endocarditis of the tricuspid valve is a rare form of valvular endocarditis and occurs mainly in patients with special risk factors. CASE REPORTS: The three case reports demonstrate 3 young patients (age 30 to 37 years, 2 female and 1 male) with a typical history of those risk factors. The two women were intravenous drug addicts and one of them had suffered already an episode of tricuspid valve endocarditis several years ago. The man developed his infection after implantation of a pacemaker. In all of the three patients the endocarditis was due to infection with staphylococci twice staphylococcus epidermidis and once staphylococcus aureus. In two of the three patients the endocarditis could not be cured by intravenous antibiotics alone and these patients had to undergo cardiac valvular surgery. All patients left the hospital after several weeks without signs of infection. CONCLUSION: In clinical praxis the introduction of a special endocarditis service, a small team which has to be consulted in every suspected case of endocarditis, seems to be beneficial as well as the use of the Duke criteria for diagnosis in those cases.

AIDS-Related Opportunistic Infections↗

Pseudoaneurysm after cardiac catheterization: therapeutic interventions and their sequelae: experience in 86 patients.

After diagnostic cardiac catheterization in 8,715 patients, a pseudoaneurysm was diagnosed in 86 (1%) patients. Primary conservative management by repeated compression bandages (CB) or ultrasound guided compression (UGC) was attempted in all patients. Occlusion of the pseudoaneurysm was achieved significantly more often by UGC (41/47; 87%) than by CB (22/39; 56%; P = 0.016). Of 86 patients, 23 (27%) required surgical treatment. Major clinical acute complications occurred after surgery in 8/23 cases (35%) versus 4/63 (6%; P = 0.0004) following successful CB or UGC. However, intention-to-treat analysis showed no difference in the rate of acute complications in the CB or UGC group (15.4% versus 12.8%, P = 0.7272), because of a trend towards a higher complication rate following secondary surgery in the UGC (4/6 = 66.7%), as compared to the CB group (4/17 = 23.5%, P = 0.1589). During follow up, 22/64 (34%) patients reported persistent inguinal complaints, 9/15 (60%) after surgery and 13/49 (27%) after successful CB or UGC (P = 0.0169). However, according to the intention-to-treat analysis, there was no significant difference between the initial groups (CB: 26.1% versus UGC: 39.0%, P = 0.2958). Despite a higher effectiveness of UGC to achieve occlusion of a pseudoaneurysm compared to CB (87% vs. 56%), UGC is not superior to CB because of a higher rate of acute complications as well as long-term complaints in those patients requiring secondary surgery in the UCG group as compared to the CB group.

Adult↗

Local venous thrombosis after cardiac catheterization.

Pulmonary embolism is a rare but life-threatening complication of cardiac catheterization. Underlying deep venous thrombosis (DVT) is often not detectable clinically. To determine the true incidence of DVT the authors prospectively studied 450 consecutive patients (29% women, 71% men, mean age: fifty-eight years) undergoing a diagnostic cardiac catheterization. Patients were examined clinically and by duplex sonography with a high-resolution (5 or 7.5 MHz) transducer before and twenty-four hours after catheterization before mobilization. Duplex sonography excluded complete proximal DVT in all patients. Only partial occluding thrombi (pDVT) were detected in 11 (2.4%) patients. The thrombi were always localized at the puncture site. In 2 patients a difference was found in the circumferences of the legs, but no other clinical signs of DVT were seen. With use of continuous wave (cw) Doppler sonography, only 3 of these 11 patients (27%) showed a spontaneous (s) sound. Phlebography was performed in 4/11 patients (36%). In 2 patients the diagnosis was confirmed; in 1 patient extravenous compression was assumed, and the other demonstrated a normal-appearing phlebography at the time of investigation. Logistic regression analysis yielded a 3.5 times higher risk for developing a pDVT if a venous puncture was performed in addition to arterial puncture. Furthermore a 9.8 times higher risk was found if more than one venous puncture was necessary. During the follow-up no patient developed clinical signs of pulmonary embolism. The results of this study demonstrate that DVT is a rare complication of cardiac catheterization (0/450 patients), but pDVT occurred in 2.4%. Risk factors for pDVT are the venous puncture itself and multiple puncture attempts. Clinical relevance of pDVT remains to be determined.

Cardiac Catheterization↗

[Feasibility and safety of dobutamine stress echocardiography: experiences with 1,000 studies].

The use of dobutamine stress echocardiography for the evaluation of coronary artery disease is rapidly expanding. Despite its widespread use, the feasibility and safety of dobutamine stress echocardiography has not been sufficiently documented. Between November 1992 and June 1995, we performed 1000 dobutamine stress echocardiographies. There were 744 men and 256 women with a mean age of 59 +/- 11 years. Anti anginal medication was not routinely withdrawn before the test. The mean maximal dobutamine dose was 41,4 +/- 10 mu g/kg center dot min(-1). Atropine was given additionally in 440 patients, with a mean dose of 0.5 mg. In patients receiving beta-blockers additional atropine was more often necessary as compared to those not receiving beta-blockers (278/457 = 61% versus 162/543 = 30 %, p < 0.0001). Reasons for discontinuing dobutamine infusion were achievement of target heart rate (64 % of cases) and maximal dose (12 % of cases). In 791 (79,1 %) patients no side-effects of dobutamine stress echocardiography were noticed. Termination of the study because of adverse side-effects occurred in 6.6 %. A total of 103 (10,3 %) noncardiac side-effects were observed: dizziness or nausea 6.4 %, headache 1.7 %. In one patient a focal cerebral seizure occurred. 156 cardiac side-effects occurred: blood pressure decrease of more than 20 mm Hg in 25 patients, extreme palpitations in 16 patients and pulmonary edema in one case. Most common cardiac side-effects consisted of arrhythmias (11.4 %): 9.1 % ventricular and 2.3 % supraventricular arrhythmias. Most ventricular arrhythmias were less severe (uniform and multiform premature ventricular beats, ventricular bigeminy or couplets in 71 patients). Nonsustained ventricular tachycardia, with a maximum duration of 20 s, occurred in 18 patients. In one patient sustained ventricular tachycardia developed and progressed towards ventricular fibrillation. This patient could be successfully defibrillated. Supraventricular arrhythmias presented as new atrial fibrillation in 10 patients, supraventricular tachycardia in three patients, junctional rhythm with a short decline in heart rate in nine patients and a second-degree AV block in another case. Dobutamine stress echocardiography has proven to be a safe and feasible method in the diagnosis of coronary heart disease. Minor side-effects are common and sometimes unpleasant for the patient, but do not often require termination of the study. Severe side-effects are seldom (< 1 %), but nevertheless, adequate medical and technical (defibrillator) support should be rapidly available.

Adult↗

Multicentre evaluation of an immunological rapid test for the detection of troponin T in whole blood samples.

In a multicentre study we assessed the analytical and diagnostic performance of a rapid test (TROPT rapid test, Boehringer Mannheim; in the USA: CARDIACT) for cardiac troponin T compared to quantitative troponin T ELISA and creatine kinase-MB mass determinations. The rapid test requires 150 microliters of heparinized or EDTA whole blood; serum is not suitable. Interference testing with biotin, haemoglobin and 27 standard drugs yielded no significant influence in the physiological range. Skeletal muscle troponin T concentrations > or = 40 micrograms/l gave positive results with the rapid test. We used the rapid test for 369 samples from 203 patients with suspected acute coronary syndromes and compared the results to troponin T ELISA and creatine kinase-MB mass. 90 patients (44%) were primarily classified as having myocardial infarction by the WHO criteria. Twenty-two (20%) of the 113 non-myocardial infarction patients were unstable angina pectoris cases showing increased troponin T ELISA but not increased creatine kinase-MB mass values. Consequently, these were classified as minor myocardial damage cases. The rapid test was positive in 99% of all samples with a troponin T ELISA value > or = 0.30 micrograms/l and negative in 95 to 96% of all samples below this value. Diagnostic sensitivities for the detection of acute myocardial infarction within the first 12 hours after onset of pain were the same, 90%, for the rapid test, troponin T ELISA and creatine kinase-MB mass. After 48 hours, diagnostic sensitivity of creatine kinase-MB mass sharply decreased whereas that of the troponin T assays remained close to 100% beyond 72 hours after onset of symptoms. Diagnostic specificities for acute myocardial infarction (WHO) of all markers remained between 80 and 100% over this time. The diagnostic sensitivity of the rapid test for the detection of high risk unstable angina pectoris patients with minor myocardial damage was nearly the same as for troponin T ELISA. A major advantage of the rapid test is the ease of use and 20 minute turn around time. This facilitates the detection of increased troponin T at alternate sites.

Biomarkers↗

Do 5-F-catheters reduce the incidence of a pseudoaneurysm?

Femoral artery pseudoaneurysm is a major problem in patients undergoing cardiac catheterization. This study describes our experience with 5 French (5 F) and 7 French (7 F) introduction sheaths and 7 investigators at our institution regarding the incidence of pseudoaneurysms. During 54 months (1/1990-6/1994) 8715 consecutive patients after diagnostic cardiac catheterization were first clinically checked for pseudoaneurysm and in case of suspicion a duplex sonography was performed. In 86 (1%) patients, 44 (52%) women and 42 (48%) men, mean age 63 +/- 9.7 years we observed this complication by duplex ultrasound. 54 (62%) patients had arterial hypertension, 18 (20%) diabetes and only 3 (3.6%) had peripheral arteriosclerosis. An antithrombotic medication was used in 60% (52 patients). As compared to a control group of 450 consecutive patients a pseudoaneurysm was significantly more likely to occur in patients with a history of hypertension (63% vs 25%, p < 0.0001). Women are also at higher risk representing 51% of all pseudoaneurysms as compared to 29% in the control group (p < 0.0001). Using 7-F catheters more pseudoaneurysms occurred (82/7183; 1%) than using 5 F (4/1532; 0.2%) introduction sheaths (p = 0.0005). There were also significantly more pseudoaneurysms caused by investigator 1 (21/787; 2.7%) as compared to the other investigators (65/7829; 0.8%), (p = 0.0002). Investigator 1 had a more distal puncture technique than the others. Pseudoaneurysms complicating cardiac catheterization occur 5-times more frequent using 7 F (1%) as compared to 5 F catheters (0.2%). Moreover distal puncture site is associated with a higher frequency of pseudoaneurysms.

Aneurysm, False↗

Tropheryma whippelii endocarditis confirmed by polymerase chain reaction.

This report concerns a patient with cardiac manifestation of Whipple's disease. For the first time, the gene that encodes the 16s rRNA of Tropheryma whippelii was identified in a native aortic valve by means of a polymerase chain reaction technique. DNA amplification gives evidence of Tropheryma whippelii as a causative organism in infective endocarditis.

Actinobacteria↗

[Takayasu arteritis--a rare differential diagnosis in aortic dissection. A case report].

A 36-year-old woman was delivered to our hospital with suspected aortic dissection from an outlying hospital in May 1994. She reported a history of acute and persistent thoracic and epigastric pain. The physical examination revealed a minor senso-motorical palsy of the left side as residuum after minor strokes occurring 12/93 and 4/94. Also, a marked hypertension (170/100 mm Hg) was present. The hematologic and blood chemical values were normal with a white cell count of 12,000, an erythrocyte sedimentation rate (ESR) of 19 mm/h and a c-reactive protein (CRP) of 2.2 mg/dl. The electrocardiogram was normal. Transthoracic- and transesophageal-echocardiography (TTE, TEE) revealed an eccentric thickening of the whole wall of the descending aorta up to the bifurcation with a stenosis at the side of the diaphragma. Those findings were confirmed by computed tomography. Because of the acute onset of symptoms and the results of the imaging procedures aortic dissection de Bakey type III was diagnosed and the patient was treated with beta-blockers. Symptoms were relieved over the following days. After 2 days a pleuric effusion developed and all inflammatory tests rose (fibrinogen 780 mg/dl, ESR 80 mm/hr, CRP 16 mg/dl). At this time the differential diagnosis of an arteritis was considered. A new TEE-study demonstrated no change, but now more attention was given to the fact that no dissection membrane could be visualized and all wall structures were thickened. In combination with the history of cerebral infarction due to carotid obstruction and the elevated laboratory values the diagnosis of Takayasu-aortitis was established and corticoid therapy was started. Within a few weeks the arterial changes diminshed markedly and the woman became free of symptoms. This case demonstrates the rare situation of an arteritis mimicking aortic dissection, in which the clinical course revealed the true diagnosis.

Adult↗

Beating neonatal rat cardiomyocytes as a model to study the role of xenoreactive natural antibodies in xenotransplantation.

The hyperacute rejection reaction of xenogeneic organs is supposed to be triggered by xenoreactive natural antibodies of the recipient organism. In an experimental set-up allowing for rapid medium exchange, primary cultures of spontaneously beating neonatal rat cardiomyocytes were challenged with dialyzed human serum containing xenoreactive natural antibodies. After adding the serum specimens, a reproducible pattern of disturbed contractility was observed: following an initial increase in beating frequency, spontaneous contractions stopped completely. This standstill was reversible in all experiments. No signs of permanent cytotoxicity were observed. The temporary cessation of contractions was prevented by raising extracellular calcium concentration, but not by extracellular electrical stimulation. After absorption of xenoreactive natural antibodies, cellular contractions ensued without interruption. Inactivated serum specimens produced similar effects on contractility, although the duration of the standstill period was significantly shorter. The same qualitative phenomenon occurred when sera of other xenogeneic species were used. These results point to a temporary functional disturbance of parenchymal cells by xenoreactive natural antibodies, whereas no chronic cytotoxicity was conspicuous in these experiments.

Animals↗

Influence of three different preparation techniques on the results of human sperm morphology analysis.

Using 158 unselected semen samples the present study has analysed how the results of sperm morphology assessment were influenced by different techniques for preparing the slides for microscopic assessment. All three techniques compared, the Papanicolaou stain (PAP), the Shorr stain (SHO) and the 'wet preparations' protocol (WET) are currently recommended by the World Health Organization for use in andrology laboratories. Mean percentages of morphologically normal spermatozoa were identical on PAP and SHO slides (31.1%), but were significantly lower in wet preparations (12.3%). Wide divergence of results obtained with the three different methods was also found with respect to the percentage of sperm with head, midpiece and tail defects and two 'indices of teratozoospermia'. For the majority of parameters assessed, linear regression analysis revealed a poor correlation between evaluations of PAP, SHO and WET slides (r values ranging from 0.01 to 0.87). We conclude that only one standard method should be recommended for the preparation of morphology slides in order to ensure inter-laboratory comparability of results and to enhance the value of sperm morphology analysis for predicting fertility.

Evaluation Studies as Topic↗

Long-term follow-up after Carpentier tricuspid valvuloplasty.

To study the long-term results of tricuspid valvuloplasty, pre- and postoperative (51 +/- 17 months) echocardiographic and catheterization data were collected from 51 patients (aged 59 +/- 9 years). Because of severe mitral stenosis all patients received a heterograft in the mitral position and underwent reconstructive tricuspid surgery with Carpentier rings. With regard to postoperative clinical outcome three patient groups were distinguished: 37 patients (group A) showed clear clinical improvement; in seven patients mild, and in three patients moderate tricuspid regurgitation persisted. A mild tricuspid stenosis of less than 4 mm Hg mean diastolic gradient was found in 11 patients. Patients in group B (n = 8) showed no clinical improvement, but there was persistence of moderate tricuspid regurgitation associated with nearly unchanged pulmonary hypertension in five patients and moderate tricuspid stenosis in two. Six patients (group C) showed deterioration of their clinical status; in two patients a severe degree of tricuspid regurgitation persisted, and four patients were first seen with a tricuspid stenosis with a mean diastolic gradient greater than 7 mm Hg. Analysis of postoperative data showed that tricuspid stenosis may develop during surgery in patients with slightly shrunken valve leaflets. Although the area of the anterior tricuspid leaflet was slightly underestimated, we found that long-term results of tricuspid valve annuloplasty with a Carpentier ring were encouraging. Doppler echocardiography for detection of tricuspid regurgitation and transvalvular pressure gradient showed results identical to hemodynamic data and is a suitable and sensitive method for evaluating postoperative results after tricuspid valve annuloplasty.

Aged↗

Controversial aspects of coronary endarterectomy.

Between 1980 and 1987, 635 patients underwent coronary bypass grafting combined with coronary endarterectomy. A total of 728 vessels were endarterectomized and grafted. There were 15 early deaths (2.3%). The mortality rate was higher (7.8%) for multiple-vessel endarterectomy (p less than 0.05). The ratio of MB fraction of creatine kinase to total creatine kinase was greater than or equal to 0.10 in 48% of the cases. The first consecutive 132 survivors were followed for an average of 16 months (range, 4 months to 5 years). No late deaths occurred. Fifty-nine unselected patients underwent postoperative recatheterization at a mean interval of 18 months. An improvement in heart wall contractility could be detected in 13 patients (16.5%) and deterioration in 14 patients (17.7%). A more detailed analysis of wall contractility showed a higher rate of improvement in the posterior wall than in the anterior wall (p greater than 0.05). Furthermore, the better the contractility before operation, the greater the rate of deterioration after operation (p less than 0.05). Despite an average of 55% of all endarterectomized vessels being occluded or severely restenosed, 90% of the patients were clinically improved. A multiparametric analysis revealed that the revascularization of myocardial areas that required endarterectomy had no significant influence with respect to clinical improvement. Endarterectomy should be limited, whenever possible, to myocardial areas with already impaired contractility. Endarterectomy of multiple branches should be treated with caution because the risk of deterioration is potentiated, with a significantly higher perioperative mortality rate.

Adult↗