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Biomedical subjects

C Schmidt

Publications and source records attributed to C Schmidt.

At least 181 records · Page 10Linked to original sources
PubMed1999

Cutaneous lupus erythematosus-treatment with pulsed dye laser.

Because of its vascular selectivity, the flashlamp-pumped pulsed dye laser (585 nm) is efficacious in the treatment of vascular lesions and is successfully used for the treatment of port-wine stains and haemangiomas in children. Based on the encouraging results with these cutaneous vascular disorders, the cutaneous lesions of patients with lupus erythematosus (LE) have now also been treated with the pulsed dye laser. Cutaneous lesions in lupus erythematosus are often difficult to treat with readily available local therapeutic methods. We report here on a group of 12 patients whose LE lesions were treated with the pulsed dye laser. In 10 patients, the LE was limited to the skin, while two patients had systemic LE (SLE). Even in the two patients with SLE, a significant improvement of skin lesions was achieved. After a mean number of 51 laser sessions, a median clearance rate of 70% was attained for nine patients. In one case, the laser treatment failed to clear the lesions. Two patients did not show any visible improvement of the lesions, but pain and itching were significantly reduced. There were few side-effects. No prolonged laser-induced scarring occurred and in only two patients was hyperpigmentation seen, which had resolved completely after 4 and 5 months, respectively. During a median follow-up of 7 months (range: 3-32 months), only one patient (after a complete clearance of the skin lesions) had a small relapse. In summary, the pulsed dye laser is an effective therapy for the treatment of superficial skin lesions in LE.

Adult↗
PubMed1999

How can the variability in ultrasound measurement of intima-media thickness be reduced? Studies of interobserver variability in carotid and femoral arteries.

A critical component in scientific studies of most biological variables is the variation or error in measurements which leads to non-identical results of repeated measurements from the same subject. The aim of this study was to investigate whether the interobserver error (s) in measurement of intima-media thickness (IMT) in carotid and femoral arteries could be decreased if the mean value obtained using two ultrasound images from each of the right and left arteries was used in the analyses instead of the mean value obtained using images from only the right artery. In addition, we wished to evaluate two different reading procedures, one based on manual tracing of echo interfaces and the other on automated edge detection. In a methodological study, 50 subjects were examined with ultrasound twice in the same day by two independent laboratory technologists. The ultrasound images were analysed in two ways: using a computerized manual tracing analysing system and an automated analysing system. When both right and left carotid arteries were examined (manual reading), the interobserver error was smaller than that determined for the examination of only the right artery, for IMTmean in both the common carotid artery (P = 0.06) and the carotid artery bulb (P < 0.05). The interobserver error was also significantly smaller for double-sided vs. one-sided examination with automated reading of IMTmean in the common carotid artery (P < 0.01) and in the carotid artery bulb (P < 0.01). The coefficient of variation (CV) for measurement in the common carotid artery decreased from 8.6% (one-sided, manual reading) to 5.3% (double-sided, automated reading). The interobserver error in measurement of IMT in the common femoral artery did not improve by examination of both right and left arteries. The results from this study show that the interobserver errors in measurement of IMT can be decreased by using ultrasound images from both the right and the left carotid arteries, and that the use of an automated analysing system greatly simplifies the reading of ultrasound images with sustained low variability.

Aged↗
PubMed1999

Evolving short-term and long-term mechanical assist for cardiac-failure -- a decade of experience in Münster.

Technological advances and growing expertise has lead to referral of much sicker patients with a greater incidence of heart failure prior to and after cardiac surgical procedures. The diversity of the heart failure patient cohort mandates a differentiated protocol for mechanical support adapted to the clinical requirements. It is desirable to have appropriate mechanical support available for different circumstances of heart failure. In this paper, we review the first decade of the Muenster University Hospital experience with the use of intra-aortic ballon pump, extracorporal membrane oxygenators, short term uni- and biventricular assist systems such as Thoratec and Medos devices, as well as long term left ventricular assist systems such as the TCI Heartmate and the Novacor system. The patient profiles, indications, contraindications, and future trends are reviewed within the framework of a contemporary university hospital Servive.

Assisted Circulation↗
PubMed1999

Left ventricular assist system support is associated with persistent inflammation and temporary immunosuppression.

BACKGROUND: In patients undergoing left-ventricular assist system support, it has not been elucidated to which extent mechanical circulatory support itself as opposed to the underlying condition of endstage heart-failure contributes to perturbation of immune homeostasis. METHODS: In eleven heart transplant candidates who had to undergo Novacor left-ventricular assist device bridging, we prospectively sampled interleukin-6, T-cell and monocyte subsets and compared them to fifteen UNOS status II patients awaiting cardiac transplantation on medical heart failure treatment as outpatients at the time of LVAS implantation/listing decision as well as 2.0+/-1.2 months and 4.5+/-2.3 months later. In order to assess deviations in both groups from normal values, thirty-two healthy subjects served as reference group. RESULTS: Patients undergoing Novacor bridging had higher C-reactive protein, leukocyte, neutrophil, and monocyte levels at all three times, and exhibited lower CD3 +, CD4+, CD3+/CD45 RO T-cell and natural killer cell counts than medically treated patients awaiting transplantation 2 months after the LVAS implantation/listing decision. In comparison to controls, both groups had higher levels of inflammatory activation and lower levels of immunocompetence at all three times. CONCLUSIONS: While both groups of endstage heart failure patients show immunological alterations compared to controls, patients who have to be bridged by the Novacor LVAS exhibit a more pronounced activation of inflammatory markers. This may be due to more advanced heart failure but the device itself also may contribute to more pronounced inflammation and a temporary suppression of immunocompetent cells.

Adult↗
PubMed1999

[Concepts for measuring quality of life in patients with chronic sinusitis].

BACKGROUND: In 1997, Benninger developed the Rhinosinusitis Disability Index (RSBI) for patients who suffered from chronic sinusitis. Its content related validity and construct related validity were established, as were its sensitivity and reliability. The aim of our study is to introduce a concept to measure quality of life in these patients according to circumstances prevalent in Germany. METHODS: The questionnaire (Rhinusitis-Beeinträchtigungs-Index, RSBI) contains 30 questions that describe the 5 aspects of quality of life. Moreover we used a standardized data sheet to acquire further information about history and diagnostic results. Using this method it is possible to specificity more precisely the patients current complaints and condition. Evaluation is possible according to complex of questions as well as simple items. The influence of treatment on quality of life can be measured as the sum of the specific scores and is expressed comprehensively in the total score. The concept of the study includes a prospective inquiry as well as before and after surgical intervention. CONCLUSION: A disadvantage of the American RSDI is that the clinical symptoms are not described in a detailed catalogue which allows the correlation of the clinical factors. Therefore we added a detailed questionnaire concerning the clinical symptoms and the individual treatment of the patient (RSBI). That permits comprehensive analysis of quality of life as it relates to different aspects of disease and different strategies in treatment.

Chronic Disease↗
PubMed1999

Tumor metastasis biopsy as a surrogate marker of response to melanoma immunotherapy.

In patients undergoing immunotherapy for metastatic melanoma, the clinical response in immunotherapeutic trials may be partial or difficult to detect. Tumor metastasis biopsy allows direct characterisation of an anti-tumor immunological response. During a phase I/II trial of granulocyte macrophage colony stimulating factor (GM-CSF) transduced autologous melanoma immunotherapy, the cellular response was examined by immunohistochemical analysis in a limited number of tumor biopsies taken from patients who either responded or progressed. Clinical response was associated with tumor infiltration by CD4+ and CD8+ T-cells, macrophages and differentiated dendritic cells (DC), and expression of HLA-DR by the tumor cells. This tumor infiltration was associated with increased melanoma-specific peripheral blood precursor cytotoxic T-lymphocyte (pCTL) and the ability to obtain tumor-infiltrating lymphocytes in vitro. In contrast, progression or a lack of clinical response was associated with a lack of T-cell and DC infiltration into the tumor tissue in all such biopsies. Macrophages and eosinophils infiltrated these tumors, while T-cells and DC were present at some distance from the tumor. These preliminary data strongly suggest that the location and extent of T-cell and DC infiltration, as well as the expression of HLA-DR by tumor cells are associated with a clinical response in this form of melanoma immunotherapy.

Adult↗
PubMed1999

Cost analysis of target-controlled infusion-based anesthesia compared with standard anesthesia regimens.

UNLABELLED: With the development of new computer-assisted target-controlled infusion (TCI) systems and the availability of short-acting anesthetics, total IV anesthesia (TIVA) has become increasingly popular. The aim of this study was to compare costs of TCI-based anesthesia with two standard anesthesia regimens. Sixty patients undergoing elective laparoscopic cholecystectomy were randomly divided into three groups. Group 1 (TIVA/TCI) received TIVA using a propofol-based TCI system and continuous administration of remifentanil; Group 2 (isoflurane) underwent inhaled anesthesia with isoflurane, fentanyl, and N2O; Group 3 (standard propofol) received fentanyl and N2O and a continuous infusion of propofol using a standard delivery system. Maintenance doses for anesthetics were adjusted according to the patient's need. Isoflurane consumption was measured by weighing the vaporizer by using a precision weighing machine. Duration of surgery and of anesthesia was similar in the three groups. Time from stopping administration of anesthetics until tracheal extubation (6+/-2 min) and stay in the postanesthesia care unit (PACU; 70+/-12 min) were shorter in Group 1 than in the Groups 2 (15+/-3 and 87+/-13 min, respectively) and 3 (10+/-4 and 81+/-14 min, respectively) (P < 0.05). Episodes of postoperative nausea and vomiting in the PACU and on the surgical ward were less common in Group 1 than in the other two groups. Intraoperative costs were higher in Group 1 ($62.19/patient; $0.55/min of anesthesia) than in Groups 2 ($16.97/patient; $0.13/min of anesthesia) and 3 ($34.68/patient; $0.32/min of anesthesia). Cost for discarded anesthetic drugs accounted for almost 18% of total intraoperative costs in Group 1. We conclude that TIVA/TCI anesthesia using propofol/remifentanil was associated with the highest intraoperative costs but the fewest postoperative side effects. An overall cost-effectiveness analysis of new anesthetic regimens must balance the direct cost of anesthetics and beneficial effects leading to improved patients' comfort. IMPLICATIONS: In today's climate of cost-consciousness, careful economic evaluation of new anesthetic regimens is necessary. A target-controlled infusion (TCI)-based total IV anesthesia (TIVA) regimen using propofol and remifentanil was compared with a standard propofol anesthesia regimen and an inhaled anesthetic technique using isoflurane. Target-controlled infusion/total IV anesthesia was associated with the largest intraoperative costs but allowed the most rapid recovery from anesthesia, was associated with fewest postoperative side effects, and permitted earlier discharge from the postanesthesia care unit.

Adult↗
PubMed1999

High thoracic epidural anesthesia, but not clonidine, attenuates the perioperative stress response via sympatholysis and reduces the release of troponin T in patients undergoing coronary artery bypass grafting.

UNLABELLED: In this prospective study, we evaluated whether high thoracic epidural anesthesia (TEA) or i.v. clonidine, in addition to general anesthesia, affects the cardiopulmonary bypass- and surgery-associated stress response and incidence of myocardial ischemia by their sympatholytic properties. Seventy patients scheduled for elective coronary artery bypass graft (CABG) received general anesthesia with sufentanil and propofol. TEA was randomly induced before general anesthesia and continued during the study period in 25 (anesthetized dermatomes C6-T10). Another 24 patients received i.v. clonidine as a bolus of 4 microg/kg before the induction of general anesthesia. Clonidine was then infused at a rate of 1 microg x kg(-1) x h(-1) during surgery and at 0.2-0.5 microg x kg(-1) x h(-1) postoperatively. The remaining 21 patients underwent general anesthesia as performed routinely (control). Hemodynamics, plasma epinephrine and norepinephrine, cortisol, the myocardial-specific contractile protein troponin T, and other cardiac enzymes were measured pre- and postoperatively. During the preoperative night and a follow-up of 48 h after surgery, five-lead electrocardiogram monitoring was used for ischemia detection. Both TEA and clonidine reduced the postoperative heart rate compared with the control group without jeopardizing cardiac output or perfusion pressure. Plasma epinephrine increased perioperatively in all groups but was significantly lower in the TEA group. Neither TEA nor clonidine affected the increase in plasma cortisol. The release of troponin T was attenuated by TEA. New ST elevations > or = 0.2 mV or new ST depression > or = 0.1 mV occurred in > 70% of the control patients but only in 40% of the clonidine group and in 50% of the TEA group. We conclude that TEA (but not i.v. clonidine) combined with general anesthesia for CABG demonstrates a beneficial effect on the perioperative stress response and postoperative myocardial ischemia. IMPLICATIONS: Thoracic epidural anesthesia combined with general anesthesia attenuates the myocardial sympathetic response to cardiopulmonary bypass and cardiac surgery. This is associated with decreased myocardial ischemia as determined by less release of troponin T. These findings may have an impact on the anesthetic management for coronary artery bypass grafting.

Adrenergic alpha-Agonists↗
PubMed1999

Milrinone modulates endotoxemia, systemic inflammation, and subsequent acute phase response after cardiopulmonary bypass (CPB).

BACKGROUND: Compromised splanchnic perfusion and the resulting intestinal mucosal injury leads to a decreased mucosal barrier function, which allows translocation of intestinal flora and endotoxemia. The authors evaluated the effects of milrinone on splanchnic oxygenation, systemic inflammation, and the subsequent acute-phase response in patients undergoing coronary artery bypass grafting. METHODS: This open, placebo-controlled randomized clinical study enrolled 22 adult patients in two groups. Before induction of anesthesia, baseline values were obtained and patients were randomized to receive milrinone (30 microg/kg bolus administered progressively in 10 min, followed by a continuous infusion of 0.5 microg x kg(-1) x min(-1)) or saline. The following parameters were determined: hemodynamics; systemic oxygen delivery and uptake; arterial, mixed venous and hepatic venous oxygen saturation; intramucosal pH (pHi); and mixed and hepatic venous plasma concentrations of endotoxin, interleukin 6, serum amyloid A, and C-reactive protein. RESULTS: Milrinone did not prevent gastrointestinal acidosis as measured by pHi, but its perioperative administration resulted in significantly higher pHi levels compared with control. Venous and hepatic venous endotoxin and the interleukin 6 concentration were reduced significantly in the milrinone group. Serum amyloid A values were attenuated in the milrinone group 24 h after surgery. No significant differences could be seen in routinely measured oxygen transport-derived variables. CONCLUSIONS: Perioperative administration of low-dose milrinone may have antiinflammatory properties and may improve splanchnic perfusion in otherwise healthy patients undergoing routine coronary artery bypass grafting.

Acute-Phase Reaction↗
PubMed1999

Contractility in humans after coronary artery surgery.

BACKGROUND: Propofol's unique pharmacokinetic profile offers advantages for titration and rapid emergence in patients after coronary artery bypass graft (CABG) surgery, but concern for negative inotropic properties potentially limits its use in these patients. The current study analyzed the effect of various propofol plasma concentrations on left ventricular (LV) contractility by means of a single-beat contractile index based on LV maximal power (PWR(max)). METHODS: The study was conducted in 30 patients after CABG surgery. Immediately after admission to the intensive care unit (ICU), four different plasma concentrations of propofol 0.65, 1.30, 1.95, and 2.60 microg/ml were established. At each concentration level, the cardiac and vascular effects of propofol were studied by combining echocardiographic data with invasively derived aortic root pressure. Preload was characterized by LV end-diastolic dimensions. Afterload was indicated in terms of indexed systemic vascular resistance (SVRI), LV end-systolic meridional wall stress (LV-ESWS), and arterial elastance (Ea). Quantification of effects on contractility was achieved by preload-adjusted PWRmax. RESULTS: Myocardial contractility did not change during a fourfold increase in propofol plasma concentration. Preload-adjusted PWRmax amounted to 3.90+/-1.75 W x ml(-2) x 10(4), 3.98+/-1.69, 3.94+/-1.70, and 3.88+/-1.72, respectively (mean+/-SD). With respect to ventricular loading conditions, propofol caused a significant reduction in both pre- and afterload. CONCLUSIONS: The current results strongly suggest that propofol lacks direct cardiac depressant effects. Nevertheless, meaningful vascular actions of propofol could be demonstrated. Significant decreases in ventricular loading conditions accounted for a marked decrease in arterial blood pressure and supported the concept that propofol in clinically relevant concentration is a vasodilator.

Coronary Artery Bypass↗
PubMed1999

Pharmacokinetic-pharmacodynamic modeling of the respiratory depressant effect of alfentanil.

BACKGROUND: Although respiratory depression is the most well-known and dangerous side effect of opioids, no pharmacokinetic-pharmacodynamic model exists for its quantitative analysis. The development of such a model was the aim of this study. METHODS: After institutional approval approval and informed consent were obtained, 14 men (American Society of Anesthesiologists physical status I or II; median age, 42 yr [range, 20-71 yr]; median weight, 82.5 kg [range, 68-108 kg]) were studied before they underwent major urologic surgery. An intravenous infusion of alfentanil (2.3 microg x kg(-1) x min(-1)) was started while the patients were breathing oxygen-enriched air (fraction of inspired oxygen [FIO2 = 0.5) over a tightly fitting continuous positive airway pressure mask. The infusion was discontinued when a cumulative dose of 70 microg/kg had been administered, the end-expiratory partial pressure of carbon dioxide (PE(CO2) exceeded 65 mmHg, or apneic periods lasting more than 60 s occurred During and after the infusion, frequent arterial blood samples were drawn and analyzed for the concentration of alfentanil and the arterial carbon dioxide pressure (PaCO2). A mamillary two-compartment model was fitted to the pharmacokinetic data. The PaCO2 data were described by an indirect response model The model accounted for the respiratory stimulation resulting from increasing PaCO2. The model parameters were estimated using NONMEM. Simulations were performed to define the respiratory response at steady state to different alfentanil concentrations. RESULTS: The indirect response model adequately described the time course of the PaCO2. The following pharmacodynamic parameters were estimated (population means and interindividual variability): EC50, 60.3 microg/l (32%); the elimination rate constant of carbon dioxide (Kel), 0.088 min(-1) (44%); and the gain in the carbon dioxide response, 4(28%) (fixed according to literature values). Simulations revealed the pronounced role of PaCO2 in maintaining alveolar ventilation in the presence of opioid. CONCLUSIONS: The model described the data for the entire opioid-PaCo2 response surface examined. Indirect response models appear to be a promising tool for the quantitative evaluation of drug-induced respiratory depression.

Adult↗
PubMed1999

Walking through a maze alters the architecture of sleep.

Human and animal studies imply that sleep is a critical period for consolidation of recent memories. Whereas the majority of researchers focussed on the procedural learning, the present human study concerns how storing of spatial information and episodic memory are linked to sleep stages. Two city mazes, a simple and a complex one, were created by means of a computer program. Local aspects of these mazes appeared as street scenes on a TV-screen. Our subjects sat in front of the screen and manoeuvered through the maze by the help of a three-button PC mouse. Thus, each subject took a 'mental walk' through an imaginary city. The task was to find various end-points and to find the way back to the starting point. Subjects of two experimental groups 'walked' through either the simple or complex city maze for eight hours. Afterwards the subjects slept in our laboratory, where their sleep stages could be measured polygraphically. Subjects who had explored the simple maze showed considerable alteration in sleep architecture. They remained significantly longer in sleep Stage 2 than subjects who had explored the complex maze. Moreover, with successful orientation in the simple maze sleep stages occurred aperiodically, whereas walking through the complex maze was associated with sleep stages in accordance with ultradian cycles, as observed in a control group. Compared to subjects of the control group who had experienced neither maze, the subjects of both experimental groups had significantly enhanced EEG sleep spindle activities. Alteration in temporal architecture of sleep and selective prolongation of sleep Stage 2 following spatial orientation point to a functional linkage between cognitive mapping of space and sleep Stage 2 with enhanced EEG spindle activity.

Activity Cycles↗
PubMed1999

Reliability and validity of a new device to measure isometric strength in polyarticular exercises.

BACKGROUND: The purpose of this study was to assess the validity of a new device to evaluate isometric strength during multi-joint exercise such as the squat or bench press. METHODS: The device used an electric motor-driven bar to simultaneously generate and measure forces during weight lifting exercises. This new device and a force platform measured the forces generated by either the motor on a fixed telescopic steel girder (passive condition) or a subject pushing vertically against the bar from three squat positions (active condition). In the passive condition, 252 measurements were made, with 3 trials for 6 bar heights and 14 bar loads. In the active condition, 8 young physically active students (age, height and body mass were 25.1 +/- 2.6 years, 179.3 +/- 7.2 cm and 82.0 +/- 9.9 kg, respectively) performed 3 maximal isometric strength (MIS) trials in each of the 3 squat exercise positions (parallel, half and quarter squat), and 3 additional MIS trials in one position randomly assigned two weeks later to test inter-day reliability. RESULTS: In the passive condition, no differences were observed between the forces measured by the force platform and the new device. The coefficient of linear regression (r) and the coefficient of variation (CV) were 1 and below 0.23%, respectively. In the active condition, the peak MIS measured was 2828 N and the values of r and CV were above 0.982 and below 5.96%, respectively. The assessment of inter-day reliability showed an r value of 0.984 and a CV of 3.98%. CONCLUSIONS: This study demonstrated that the new electric motor-driven exerciser provides valid and reliable data when used to generate forces and measure isometric strength throughout the load and motion ranges commonly used in squat exercise.

Adult↗
PubMed1999

Microspheres based detoxification system: in vitro study and mathematical estimation of filter performance.

Because of the closed plasma (secondary) circuit in the Microspheres based Detoxification System (MDS), a convective blood purification system, the same amount of filtrated plasma is backfiltrated into the blood circuit. Therefore, there is no direct way to determine the ultrafiltrate production rate, which is an important factor of efficiency. The only possible way to estimate the filtration properties of the filter is to consider pressure values. In this study the pressure distribution in the filter was investigated in vitro. To explain the results and to calculate inaccessible parameters, a mathematical model was established which also considered the asymmetric behaviour of the filter membrane. The result was a linear pressure gradient, agreement with the measurements was reasonably good (calculated primary pressure loss differs <13% from measured value when using mean measured filter resistance as model parameter). Linear pressure distribution offers the possibility of easily calculating the filtration length, a parameter which can be used to estimate the filter condition. The comparison between calculated filtration and backfiltration rates offers an instrument of control for these values.

Adsorption↗
PubMed1999

The influence of different intravascular volume replacement regimens on renal function in the elderly.

UNLABELLED: Elderly patients are at risk of developing renal dysfunction. Synthetic colloids are often used perioperatively, but they may have detrimental effects on renal function. In a prospective, randomized study, we assessed the influence of different intravascular volume replacement regimens on renal function in elderly (>65 yr) and younger (< 65 yr) patients without preoperative renal dysfunction who were undergoing major abdominal surgery. Either 6% low molecular weight hydroxyethyl starch (HES) solution (mean molecular weight 70,000 D, degree of substitution 0.5; HES 70/0.5) [each group n = 10]), 6% medium-molecular weight HES (molecular weight 200,000 D, degree of substitution 0.5 (HES 200/0.5) [each group n = 10]), or modified gelatin (molecular weight 35,000 D [each group n = 10]) was administered to maintain mean arterial blood pressure >65 mm Hg and central venous pressure between 10 and 14 mm Hg. After the induction of anesthesia (T0); at the end of surgery (T1); 4 h after surgery (T2); and on the first (T3), second (T4), and third postoperative days (T5), alpha1-microglobulin (alpha1-M), N-acetyl-beta-glucosaminidase, fractional sodium clearance, and creatinine clearance (CC) were measured. Colloids (1300-3000 mL) were infused until the first postoperative day. At T0, urine concentrations of alpha1-M were higher in the elderly than in the younger patients in all groups (P < 0.05). alpha1-M remained increased only in the gelatin group. N-acetyl-beta-glucosaminidase and fractional sodium clearance were not affected during the study period in any groups. At baseline, CC was significantly higher in the younger than in the elderly patients, but CC did not decrease in any of the intravascular volume replacement groups. We conclude that intravascular volume therapy with gelatin and two different HES preparations did not adversely affect renal function in elderly patients without preoperative renal malfunction. IMPLICATIONS: We studied the influence of three different intravascular volume replacement regimens on renal function in elderly patients without renal dysfunction who were undergoing major abdominal surgery. Two hydroxyethyl starch and one gelatin preparation were administered perioperatively to maintain stable hemodynamics. As assessed by sensitive markers of renal function, all three regimens can be used safely for volume replacement without risking significant renal dysfunction.

Abdomen↗
PubMed1999

Effects of acarbose treatment in Type 2 diabetic patients under dietary training: a multicentre, double-blind, placebo-controlled, 2-year study.

This 24-months, placebo-controlled, double-blind, randomised, group comparison study investigated the effect of acarbose vs placebo for improving metabolic control in patients with Type 2 diabetes under dietary training insufficiently controlled by diet alone. Patients randomised to acarbose had their dose increased in a stepwise manner to week 5. From week 5 onwards, they received 100 mg three times daily. This incremental dosing scheme was matched in the placebo group. All patients received specialist, intensive, continuous dietary training and counselling throughout the 2 yr of the study. Of the 74 patients randomised, 60 were included in the per-protocol analysis (28 receiving acarbose; 32 receiving placebo). HbA1c was the primary target variable. Per-protocol analysis found that, after 24 months, the mean difference in HbA1c relative to baseline value was -1.71+/-1.6% in the acarbose group and -0.82+/-1.1% in the placebo group. End-point values were 6.85+/-1.7% in the acarbose group and 7.41+/-1.1% in the placebo group. This difference between acarbose and placebo was statistically significant (p=0.02). Patients were defined as responders if they did not require additional treatment with an antidiabetic agent during the study. The responder rate under acarbose therapy was 89%, compared with 47% for placebo (p=0.0005). Acarbose-treated responders improved their HbA1c level to 6.45+/-0.82% after 24 months. The efficacy of acarbose was consistent throughout the study; decreasing efficacy was not evident. The results demonstrate the efficacy of acarbose for improving metabolic control in patients with Type 2 diabetes, even when such patients receive good dietary treatment and counselling.

Acarbose↗
PubMed1998

Experimental induction of BMP-4 expression leads to apoptosis in the paraxial and lateral plate mesoderm.

In the avian embryo, epithelialization of the segmental plate and formation of an epithelial dermomyotome depend on signals from the neural tube and the ectoderm overlying the paraxial mesoderm. In this study, we report that ectoderm removal in combination with barrier insertion between the axial organs and the segmental plate leads to an induction of BMP-4 expression in the paraxial mesoderm. In the lateral plate, ectoderm removal alone leads to an increase of BMP-4 expression. Application of BMP-4 protein results in a lack of epithelialization of the paraxial mesoderm. In order to investigate whether the loss of epithelial structures after these manipulations can be attributed to a change in cell fate, a change in cell proliferation, or the induction of apoptosis, the paraxial mesoderm was tested for expression of Msx-2, BMP-2, BMP-4, and BMP-7. Moreover, BrdU and TUNEL staining were carried out. The inhibition of epithelialization after ectoderm removal alone and after segregation of the axial organs is accompanied neither by an increase in apoptosis nor by a reduction of the proliferation rate in the paraxial mesoderm. On the other hand, an ectopic BMP-4 expression in the paraxial mesoderm after ectoderm removal in combination with barrier insertion coincides with the occurrence of apoptotic cells and reduction of proliferation rate in this tissue. Increase of apoptosis and decrease in cell proliferation are observed in the paraxial and lateral plate mesoderm also after application of BMP-4 protein.

Animals↗