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Biomedical subjects

A Haupt

Publications and source records attributed to A Haupt.

At least 19 recordsLinked to original sources
PubMed2005

InDuo, a novel combined insulin injection and blood glucose monitoring device - effective and save as other devices, and patient preference.

BACKGROUND AND AIM: Frequent blood glucose (BG) monitoring and insulin administration are necessary in intensive insulin regimes. A new integrated system, InDuo is a compact and portable combined insulin doser and BG monitor, designed to overcome some of the limitations of current insulin therapy. The aim of the study was to compare InDuo and a non-integrated system (HumaPen Ergo and Accu-Chek Sensor Meter) for efficacy and safety, and to evaluate patients preference. MATERIALS AND METHODS: The trial design was a multicentre, randomised, 12-week, open-label, comparative, two period crossover. One hundred and ten patients with diabetes, treated with a basal bolus regime, were included. The subjects were assigned to use either InDuo or the non-integrated system. After six weeks of treatment, the subjects were transferred to the alternative system. To assess efficacy, fasting plasma glucose (FBG), 7-point blood glucose profile, serum fructosamine and HbA1c were measured. Serum fructosamine and FBG were measured at baseline and at six and 12 weeks; HbA1c was measured at baseline and week 12. Safety endpoints were number and severity of hypoglycaemic episodes, adverse events and adverse device effects. Patient preference was assessed by a comparative device questionnaire at 12 weeks. RESULTS: Analysis with an ANOVA mixed model showed no difference after each treatment between serum fructosamine or between FBG levels. HbA1c decreased during the trial from 7.5 % +/- 1.2 to 7.1 % +/- 0.8 at 12 weeks. The safety profiles were similar for both treatments for hypoglycaemic episodes. The incidence of adverse events was also similar. There were 10 adverse device effects reported: eight for the Innovo device in the InDuo, one for the InDuo device and one for the Accu-Chek Sensor Meter. The comparative device questionnaire at 12 weeks showed patients strongly preferred InDuo to HumaPen Ergo and Accu-Chek Sensor Meter (all p < 0.0001). Of those preferring InDuo, more than 60 % classified their choice as very or extremely strong. Both memory functions in InDuo(R) (i. e., for insulin dosage and for blood glucose readings) were used by more than 70 % of the patients. CONCLUSION: Treatment with the InDuo system was as effective and safe as treatment with the non-integrated system. Almost 75 % preferred using InDuo to the non-integrated HumanPen Ergo and Accu-Chek Sensor Meter.

Adult↗
PubMed2005

The effects of skin temperature and testing site on blood glucose measurements taken by a modern blood glucose monitoring device.

BACKGROUND: Modern blood glucose (BG) monitoring devices (e.g., InDuo [LifeScan, Inc., Milpitas, CA]) require very low blood volumes, allowing for testing at sites other than the traditional fingertip, but the reliability of such testing has not been fully elucidated. The aim of this randomized study was to compare the effects of cold/warm skin temperature combined with alternative site (forearm) testing versus conventional fingertip measurements on fasting and postprandial conditions. MATERIALS AND METHODS: The study population consisted of 19 patients who had previously used InDuo for 6 weeks. Four simultaneous (within 1 min) BG readings (left and right forearm and fingertips) were obtained from each patient 15, 10, and 5 min before eating. Ten minutes before eating, the patient immersed one arm in cold water (15.5 degrees C) and the other in warm water (35 degrees C). At time 0 min arms were removed from water baths, and the patient was offered a standard meal (duration 15 min). Arms were again immersed in water baths, and BG was measured from the same locations 20 min after eating and at subsequent 15-min intervals for 185 min. The effects of site testing and temperature were assessed in this period by identifying maximum BG concentrations (C (max)) and time to C (max) (T (max)). RESULTS: Significantly lower Cmax values were observed for (1) cold forearm versus cold fingertip (mean Delta 28.6 mg/dL, P < 0.001), (2) warm forearm versus warm fingertip (mean Delta 12 mg/dL, P = 0.028), (3) cold fingertip versus warm fingertip (mean Delta 17.2 mg/dL, P = 0.002), and (4) cold forearm versus warm forearm (mean Delta 33.7 mg/dL, P < 0.001). Significantly longer Tmax values were reported for cold forearm versus warm forearm (mean Delta 22.4 min, P < 0.001) and cold forearm versus cold fingertip (mean Delta 20 min, P < 0.001). CONCLUSIONS: These results demonstrate that cold skin and forearm conditions significantly underestimate BG concentrations and delay T(max) compared with warm skin and fingertip measurements.

Blood Glucose↗
PubMed2001

Endoscopic lithotripsy with a new device combining ultrasound and lithoclast.

BACKGROUND AND PURPOSE: Endoscopic lithotripsy is still the method of choice for a number of stones, especially large stones. Various disintegration techniques exist. We investigated the combination of two of these techniques: ultrasound and pneumatic lithotripsy. PATIENTS AND METHODS: Fourteen consecutive patients with renal and one patient with bladder stones were treated with this new device. Ultrasound and pneumatic lithotripsy could be used independently or simultaneously. RESULTS: Disintegration and stone removal was fast. The use of forceps or other instruments could generally be avoided. No complications attributable to the lithotripsy device were observed. CONCLUSION: The combined ultrasound/pneumatic lithotripsy device is safe and highly effective. It reduces treatment time and enhances surgeon's comfort.

Adult↗
PubMed1999

Synthesis and cytostatic activities of didemnin derivatives.

The highly cytostatic didemnins contain a 23-membered cyclopeptolide with a side chain attached to the backbone through the amine group of threonine. Thirty-six derivatives varying the side chain were prepared, but only compounds with D-MeLeu attached to threonine show remarkable biological activities. To protect the macrocycle from degradation by lipases the two ester bonds were replaced successively by amide bonds. Although these variations have a major effect on the conformation and rigidity of the ring, the compound which contains exclusively amide bonds is highly active, equivalent to acetyl-didemnin A.

Antineoplastic Agents↗
PubMed1999

The KID Study V: the natural history of type 2 diabetes in younger patients still practising a profession. Heterogeneity of basal and reactive C-peptide levels in relation to BMI, duration of disease, age and HbA1.

In a detailed evaluation of the data accumulated for 493 type 2 diabetics who participated in the KID Study, pre- and postprandial C-peptide was correlated with blood glucose level, HbA1, body mass index (BMI), duration of disease and age. As described earlier the KID-Study examined a younger cohort of type 2 diabetics predominately practising a profession. Our investigations demonstrate a significant increase of pre- as well as postprandial C-peptide levels with increasing obesity. However, delta C-peptide, as an indicator at the reaction capacity of pancreatic secretion, decreases significantly and continuously. Pre- as well as postprandial C-peptide levels decrease significantly with up to 15-20 years duration of disease. The preprandial pancreatic secretion is usually even at a high normal level at such a late stage whereas the secretory reserve of normal or mildly overweight as well as of obese type 2 diabetics is more impaired. In contrast to patients with a BMI < 30, obese patients with a BMI > 30 will also develop impairment of basal insulin secretion over decades. The patient's age did not influence the pre- or postprandial insulin secretion. The quality of metabolic control as measured by the HbA1 has nearly exclusive impact on the secretory reserve capacity. Correlation with increasing HbA1 concentrations, the postprandial but not the preprandial C-peptide levels decreased significantly and continuously. Predictive factors for a deterioration in pancreatic function are in order of importance: the extent of obesity, the quality of metabolic control and only last the duration of diabetes. Fortunately, consistent diabetic care can have an impact on the first two.

Age of Onset↗
PubMed1999

The KID Study VI: diabetic complications and associated diseases in younger type 2 diabetics still performing a profession. Prevalence and correlation with duration of diabetic state, BMI and C-peptide.

A sub-study evaluated 698 younger (54.5 +/- 6.9 years) type 2 diabetics of the KID Study participants to establish the prevalence of diabetic complications and associated diseases and their correlation with body mass index (BMI), duration of disease and to C-peptide levels. Only 19.8% of the type 2 diabetics had a normal weight. In all weight subgroups, the average age of diabetes manifestation were around age 45. In 46.6% of all type 2 diabetics we could already demonstrate microangiopathic complications. Strikingly, 15.9% of the patients already had proliferative retinopathies and 12.6% had albuminuria of more than 1000 mg/dl. 74.7% of our type 2 diabetics presented with the well-known risk cluster of the metabolic syndrome: In every other patient, we found hypertension and/or hyperlipoproteinaemia. Accordingly, the prevalence of the macroangiopathic diabetic complications, coronary artery disease and peripheral vascular disease was 17.8%, which is high for a relatively young population with a mean age of 53.9 years and goes conform with recent literature (Lowel et al., 1999). An increase in BMI correlated significantly with deterioration of HbA1, a decrease in HDL cholesterol, an increase in triglycerides and with a higher prevalence of hypertension. The frequency of nephropathy increase significantly up to a BMI of 30-35 kg/m2. Retinopathies and polyneuropathies were associated with BMI but increased significantly with the duration of the diabetic state. In contrast to microangiopathic diabetic complications, there was already a high prevalence of nephropathy after a comparatively short duration of disease. The prevalence of hyperlipoproteinaemia and hypertension did not depend from the duration of diabetes. These concomitant diseases already were frequent early in the disease and did not increase with the duration of disease. However, there was a strong correlation between increasing hyperlipoproteinaemia and hypertension and higher C-peptide levels. We found no coincidence between C-peptide levels and microangiopathic diabetic complications.

Adult↗
PubMed1997

Polymorphisms in the PMP-22 gene region (17p11.2-12) are crucial for simplified diagnosis of duplications/deletions.

DNA duplications and deletions of a 1.5-Mb region in chromosome 17p11.2-12 comprising the gene encoding peripheral myelin protein 22 (PMP-22) are the common mutations in Charcot-Marie-Tooth disease type 1 (CMT1) and hereditary neuropathy with liability to pressure palsies (HNPP). A 1.7-kb recombination hotspot region has been identified within misaligned flanking repeats (CMT1-REP elements) by detection of CMT- and HNPP-specific junction fragments in Southern blot analyses. In order to simplify routine diagnosis we introduce a polymerase chain reaction-based method to identify directly specific REP junction fragments. Using this test, specific fragments were detected in approximately 67% of both CMT duplication and HNPP deletion cases. Polymorphism within a specific restriction enzyme recognition site is crucial for both Southern blot and PCR analyses of junction fragments.

Blotting, Southern↗
PubMed1997

The KID study IV: effects of inpatient rehabilitation on the frequency of glucose self-monitoring, quality of further primary care, on time being unable to work and on everyday psychic strain of type I and type II diabetics--a one-year follow-up. Kissingen Diabetes Intervention Study.

The Kissingen Diabetes Intervention Study (KID) evaluated 1,050 diabetic patients of the German Federal Insurance Institution for Salaried Employees (BfA) admitted for inpatient rehabilitation in a single-center, prospective, longitudinal study which was carried out to collect data concerning the structure of the patient cohort, socioeconomic factors, psychological data and state of medical care by consecutively registered random tests. These results have already been published. We will now report on the outcome 6 and 12 months after inpatient treatment. Consisting of rather young diabetics in higher professional standing, our patient cohort is especially interesting for health policy. The numbers of type I diabetics and of insulin-treated type II diabetics who self-monitor blood glucose levels several times daily significantly increased after inpatient rehabilitation. This situation is maintained 6 and 12 months after discharge. The number of type II diabetics on diet or oral hypoglycemics who do not monitor urinary glucose levels at all, is significantly reduced. The frequency of daily or weekly checks is significantly raised even after 12 months. Due to inpatient diabetic education, self-monitoring of glucose levels plays a more important role in primary care of these patients. 68.5% of all type I and about 60% of all type II diabetics receive test material without problems and are encouraged to continue monitoring. However, about 30% of type I and type II diabetics under primary-care management are still supplied with test material only when especially demanding it. The frequency of consultations in primary care diabetic management remains unchanged after inpatient treatment. The quality of diabetic management in primary care is improved by patient education. Monitoring of HbA1 is significantly increased in type I diabetics and significantly increased in type II diabetics. A similar development is seen in monitoring urinary albumin excretion but here are still deficits. For type II diabetics, the body weight and serum lipids are increasingly controlled main parameters. But in many places and especially in the case of type II diabetics the fasting glucose level is still used as main parameter. Compared with the 6 months prior to inpatient treatment, times when type I and type II diabetics are unable to work are significantly reduced in the 6 months and 12 months after-wards. Evaluating individual profiles of psychosocial strain shows that the more intense confrontation with problems of the disease and demands of the treatment can lead to a poorer quality of life in several categories. This was seen in the categories anxiety, depression, fear of hypoglycemias in the case of type I diabetics, restriction of leisure time activities, relationship with the partner and acceptance of disease. Only in the categories patient-physician relationship and professional strain was an improvement found. These alterations are still demonstrable after 6 and 12 months.

Absenteeism↗
PubMed1997

Treatment of brain metastases in patients with testicular cancer.

PURPOSE: Despite improved cure rates for patients with metastatic testicular cancer with cisplatin-based combination chemotherapy, patients who develop brain metastases are generally considered to possess a poor prognosis. This report summarizes the long-term results in 44 patients with brain metastases from testicular cancer treated between 1978 and 1995 at Hannover University Medical School. PATIENTS AND METHODS: Histologically, 42 patients (95%) had a nonseminomatous germ cell cancer and two patients (5%) a seminoma. Thirty-nine patients (89%) had lung metastases and 37 (84%) fulfilled the criteria for advanced disease according to the Indiana University classification even without considering the brain metastases. Eighteen patients (41%) presented with brain metastases at primary diagnosis (group 1), four (9%) developed brain metastases at relapse after a previous favorable response to combination chemotherapy (group 2), and 22 (50%) developed brain metastases during or directly after cisplatin-based chemotherapy. Chemotherapy consisted of cisplatin-based combination treatment and radiotherapy was given as whole-brain irradiation of 30 to 40 Gy and in single cases combined with a boost of 10 Gy to single lesions. RESULTS: Overall, 10 patients achieved long-term survival (23%; 95% confidence interval [CI], 10.1% to 35.4%). The prognosis was significantly better for patients in groups 1 and 2, with six of 18 (33%) and three of four (75%) patients alive, compared with only one of 22 (5%) in group 3 (P < .01). Patients treated with either chemotherapy or radiotherapy alone did not achieve long-term survival, while nine of 28 (32%) who received treatment with both modalities with or without surgery achieved sustained long-term survival. During univariate analysis, patients with the diagnosis of brain metastases at first presentation (P < .01), patients with a single brain lesion (P < .02), and patients who received combined chemotherapy and radiotherapy (P < .03) had a significantly improved outcome. CONCLUSIONS: Long-term survival can be achieved in approximately 25% of patients with brain metastases from testicular cancer by combined treatment with brain irradiation and aggressive cisplatin-based chemotherapy. Patients who develop brain metastases during systemic treatment should receive only palliative radiation therapy, since sustained survival will not be reached.

Adolescent↗
PubMed1996

The KID Study. I: Structural baseline characteristics of the Federal Insurance for Salaried Employees' Institution (BfA) diabetic patients in inpatient rehabilitation. Kissingen Diabetes Intervention Study.

% of type I diabetics are not administering insulin according to the intensified conventional therapy schedules, only 16.8% of all type II diabetics are treated with diet only. Type II diabetics are much too often treated with pre-mixed insulins of too high dosage (26.2%) or with oral hypoglycemics (46.2%) of which 90% were sulphonylureas and nearly exclusively glibenclamide. Oral hypoglycemics with extrapancreatic activity or combined therapies were not common among the patients.

Adult↗
PubMed1996

The KID Study. II: Socioeconomic baseline characteristics, psycho-social strain, standard of current medical care and education of the Federal Insurance for Salaried Employees' Institution (BfA) diabetic patients in inpatient rehabilitation. Kissingen Diabetes Intervention Study.

The Kissingen Diabetes Intervention Study (KID) evaluated 1050 diabetic patients of the German Federal Insurance for Salaried Employees' Institution (BfA) admitted for inpatient rehabilitation. A single-center prospective, longitudinal study collected data concerning baseline characteristics of patient cohort, socioeconomic factors and mode of intervention at the time of admission, discharge and outcome 6 and 12 months after discharge with consecutively obtained random tests. This cohort of patients is especially interesting for aspects of health policy because it is composed of rather young diabetics engaged in professional work. The data suggest that on the one hand considerably fewer type I diabetics than type II diabetics are married, but that on the other hand constant relationships are equally common in both groups when not considering the marital status. 70% of all diabetics have regular working hours, only 10% of the type II diabetics and negligible 3.9% of the type 1 diabetics work nightshifts. Nevertheless, 29.4% of the type I diabetics and 36.4% of the type II diabetics were unfit for work for at least 4 weeks in the 6 months prior to admission. Only 35.5% of all diabetics see their doctor once or twice monthly. The disease was first diagnosed by the general practitioner in 70% of all cases. Thorough information concerning the disease was provided only in 33.7% of type II diabetics and 26.1% of type I diabetics. 50.6% of type I diabetics and 68.4% of type II diabetics did not receive any education during the all important first year after diagnosis. Most of the diabetic education which had taken place was provided by general hospitals but also by specialized diabetes hospitals and rehabilitation hospitals. 65.6% of all type II diabetics do not monitor urine glucose and those who do so, monitor only once to twice weekly or less. Fortunately 96.3% of all type I diabetics monitor blood glucose, but only 41.0% of them monitor as frequently as is appropriate. 28.3% receive material for monitoring glucose levels only after asking for this. In 32% of the type II diabetics monitoring urine glucose, the general practitioner does not discuss the results with them. Regular controls of glycolysated hemoglobin is part of the diabetic management in 84.4% of all type I diabetics, but carried out in only 34.9% of all type II diabetics, among which the checking of fasting glucose dominates laboratory controls with 50.9%. However, blood lipids are monitored in half of the patients. Huge deficits have been found in the monitoring of urinary albumin excretion in type I diabetics, but especially in type II diabetics. Fear of the future and depression are the predominant strains in everyday life for type I diabetics as well as for type II diabetics. Next most important is the fear of hypoglycemias for type I diabetics, who also feel significantly more restricted in leisure time activities than type II diabetics do. No difference was found between the two groups concerning the demands of treatment. Differences were marked in that more type I than type II diabetics complain of strain in professional life due to their disease, and that a higher proportion of type II diabetics feel impaired by physical complaints (higher incidence of multimorbidity) and consider their relationships more strained by the diabetes than type I diabetics. Surprisingly, problems with accepting the disease and problems in the doctor-patient relationship were of similarly low importance in both groups. We will soon report the changes of the parameters discussed here found after inpatient rehabilitation with intensive diabetic education, promotion of physical activities and psychological measures.

Adult↗
PubMed1996

The KID Study. III: Impact of inpatient rehabilitation on the metabolic control of type I and type II diabetics--a one-year follow-up.

The Kissingen Diabetes Intervention Study (KID) evaluated 1050 diabetic patients of the German Federal Insurance Institution for Salaried Employees (BfA) admitted for inpatient rehabilitation. The data for the prospective longitudinal study (which was collected in a single center) relate to the structure of the patient cohort, socio-economic and psychological factors and the mode of medical management at the time of admission and discharge. Data regarding the same variables was checked by random testing six and twelve months after discharge and used in this part of the study. This cohort of patients is especially interesting for aspects of health policy because it comprises rather young diabetics engaged in highly qualified professional work. Therapy modifications entailing a more intensive insulin regimen were necessary in 20.7% of all type I diabetics. Most of these alterations were maintained over the following 12 months of management by the general practitioner. Improvement of HbA1 levels was related to the number of daily insulin administrations. The results obtained during inpatient treatment in patients on ICT are maintained even one year after their discharge. For type I diabetics, the first training measure especially results in a long-term improvement of the metabolic situation, whereas patients who have already received training several times previously benefit continuously less with increasing repetition of training. After twelve months the intensified insulin therapy of type I diabetics had no further effect on the BMI or the already previously normal serum lipids. In 55.5% of all type II diabetics, the therapy had to be modified. Inpatient rehabilitation resulted in raising the low number of type II diabetics treated just with diet by 5.3%. This proportion was again slightly reduced 12 months later. During inpatient residence the number of overweight type II diabetics treated with drugs was reduced both in the group on oral hypoglycemics and in the group on pre-mixed insulin, according to the weight loss achieved. On the other hand, it was often necessary to intensify the usual insulin regimen twice daily in the group of younger patients with normal body weight. These modifications were maintained twelve months after the stay in hospital for most of these patients. Virtually all type II diabetics on oral hypoglycemics are overweight as a reflection of too early prescriptions of oral hypoglycemics which often neglects the chance of a dietary management only. In this group, therapy modifications were directed towards treatment with diet only and with oral hypoglycemics having an extra-pancreatic action. On metformin, the HbA1 was reduced by 0.3% and the BMI by 0.9 kg/m2 even 12 months later. In the 90% of type II diabetics previously treated with sulphonylureas (almost exclusively glibenclamide), re-modification of therapy from metformin back to the old regimen (16:9%) was especially high. This is probably due to the uncertainty with and general restrictions in the prescription of metformin in the relevant period 1991 to 1995. The results 12 months after inpatient treatment show the small improvement of HbA1 and serum lipids as already seen in other larger interventional studies. The BMI does not change significantly within the relatively short follow-up period. The best long-term results are achieved by a combined therapy with sulphonylurea compounds and metformin. The KID study demonstrates major deficits in intensifying the insulin regimen of type I diabetics and in the individual adaptation to therapy of type II diabetes in Germany, even when younger patients of higher professional status are considered. Interventional inpatient rehabilitation improves their metabolic situation with lasting effect and can compensate deficits in outpatient management by the general practitioner. However, future concepts have to be improved at all levels of diabetic management, with a view to achieving an optimum interaction.

Body Mass Index↗
PubMed1996

A randomized trial of cisplatin, etoposide and bleomycin (PEB) versus carboplatin, etoposide and bleomycin (CEB) for patients with 'good-risk' metastatic non-seminomatous germ cell tumors.

BACKGROUND: Cisplatin-based combination chemotherapy will cure 70% to 80% of patients with metastatic non-seminomatous germ cell tumors but is associated with the possibility of severe neuro-, oto- and nephro-toxicities. Carboplatin, a cisplatin analogue, is an active drug in testicular cancer with a more favourable spectrum of side effects. In a randomized trial, the German Testicular Cancer Study Group compared a combination regimen of carboplatin, etoposide and bleomycin (CEB) to standard cisplatin, etoposide and bleomycin (PEB) chemotherapy for patients with 'minimal-' and moderate-disease' non-seminomatous germ cell tumors, according to the Indiana University classification. PATIENTS AND METHODS: PEB was given for three cycles at standard doses (given days 1-5), and the CEB regimen consisted of carboplatin (target AUC of 5 mg/ml x min) on day 1, etoposide 120 mg/m2 on days 1 to 3 and bleomycin 30 mg on days 1, 8 and 15. Four cycles of CEB were given, with the omission of bleomycin in the fourth cycle. Thus, the cumulative doses of etoposide and bleomycin applied in the two treatment arms were comparable. Fifty-four patients were entered on the trial, 29 were treated with PEB and 25 with CEB chemotherapy. Patients were stratified according to disease extent (minimal versus moderate) and the degree of tumor marker elevation. Thirty-two patients (59%) belonged to the group with minimal disease and low markers. RESULTS: No significant difference in response to chemotherapy was seen between the two arms, with CR rates of 81% for the PEB arm and 76% for CEB treatment. However, more patients treated with CEB (32% versus 13%) have relapsed after therapy, and 4 patients (16%) have died of disease progression after CEP in contrast to 1 (3%) after PEB therapy. The first interim analysis of negative events (relapse, vital tumor at secondary resection, death from disease and therapy-associated death) showed a significantly higher rate after CEB than after PEB therapy, and the trial was terminated early. After a median follow-up of 33 months for all patients, the calculation of negative events is still significantly in favour of PEB-treated patient, particularly since three late relapses > 2 years have been observed in the CEB arm (P = 0.03). CONCLUSION: This randomized trial demonstrates that even with the use of adequate doses of etoposide and full-dose bleomycin, carboplatin cannot altogether replace cisplatin in patients with testicular cancer. Treatment with the PEB regimen remains the standard approach in patients with 'good-risk' non-seminomatous germ cell tumors.

Adolescent↗
PubMed1995

LU103793 (NSC D-669356): a synthetic peptide that interacts with microtubules and inhibits mitosis.

LU103793 (NSC D-669356) is a new synthetic derivative of Dolastatin 15, an antiproliferative compound which was isolated from the mollusk Dolabella auricularia. Like Dolastatin 15, LU103793 is highly cytotoxic in vitro (IC50 = 0.1 nM). To investigate the mechanism of action of LU103793, we used a combination of biochemical and cellular methods. Turbidity assays with bovine brain microtubules demonstrated that LU103793 inhibits microtubule polymerization in a concentration-dependent manner (IC50 = 7 microM). Treatment with this compound also induced depolymerization of preassembled microtubules. Cell cycle analysis of tumor cell lines treated with LU103793 indicated a block in the G2-M phase. At the cellular level, it induced depolymerization of microtubules in interphase cells and development of abnormal spindles and chromosome distribution in mitotic cells. Although these effects are very similar to the cellular alterations caused by vinblastine, LU103793 does not inhibit vinblastine binding to unpolymerized tubulin in vitro. Our results suggest that LU103793 exerts its cytotoxic activity primarily through disruption of microtubule organization.

Adenocarcinoma↗