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Biomedical subjects

S Freytag

Publications and source records attributed to S Freytag.

12 recordsLinked to original sources

[Allocating and scheduling operating room time].

During the past decade many scientific advances have been made concerning the development of methodologies to maximize efficiency of surgical facilities through allocating and scheduling of operating rooms. In this article such a methodology is described. Using the analysis of historical data of surgical activity in a facility, future demand is predicted and planned. Part of the methodology includes principles and rules needed for the daily organization and operative management of surgical facilities. They are also derived from the same science and therefore the basis for rational and structured decision making. Medical aspects such as patient safety and free choice of day for surgery have higher priority than the economic goal of maximizing operating room efficiency.

Efficiency, Organizational↗

Cyclandelate in the prophylaxis of migraine: a placebo-controlled study.

The prophylactic action of cyclandelate was investigated in a multicentre, randomized, placebo-controlled, parallel group study. A 4-week baseline period was followed by a 4-week placebo phase and a 16-week treatment period with either 1600 mg cyclandelate or placebo. Patients (n = 251) with two to six migraine attacks/month were randomized. Neither the primary study endpoint (reduction of migraine days from baseline to the last 28 days) nor most of the secondary endpoints (reduction in the number of migraine attacks, severity or duration of attacks, frequency of autonomic disturbances, medication for treatment of attacks) showed a difference between cyclandelate and placebo. Cyclandelate, however, was superior to placebo in a global impression of efficacy rated by the patients and the treating physicians. Both treatments were well tolerated. In conclusion, cyclandelate was not superior to placebo in the prophylaxis of migraine with regard to parameters usually used in migraine prophylaxis trials.

Adolescent↗

Antisense GLUT-1 protects mesangial cells from glucose induction of GLUT-1 and fibronectin expression.

A stable clone of rat mesangial cells expressing antisense GLUT-1 (i.e., MCGT1AS cells) was developed to protect them from high glucose exposure. GLUT-1 protein was reduced 50%, and the 2-deoxy-[(3)H]glucose uptake rate was reduced 33% in MCGT1AS. MCLacZ control cells and MCGT1 GLUT-1-overexpressing cells were used for comparisons. In MCLacZ, 20 mM D-glucose increased GLUT-1 transcription 90% vs. no increase in MCGT1AS. Glucose (8 mM) and 12 mM xylitol [a hexose monophosphate (HMP) shunt substrate] did not stimulate GLUT-1 transcription. An 87% replacement of the standard 8 mM D-glucose with 3-O-methylglucose reduced GLUT-1 transcription 80%. D-Glucose (20 mM) increased fibronectin mRNA and protein by 47 and 100%, respectively, in MCLacZ vs. no increases in MCGT1AS. Fibronectin synthesis was elevated 48% in MCGT1 and reduced 44% in MCGT1AS. We conclude that 1) transcription of GLUT-1 in response to D-glucose depends on glucose metabolism, although not through the HMP shunt, and 2) antisense GLUT-1 treatment of mesangial cells blocks D-glucose-induced GLUT-1 and fibronectin expression, thereby demonstrating a protective effect that could be beneficial in the setting of diabetes.

ATP-Binding Cassette Transporters↗

[Australian Refined Diagnosis Related Groups. Formal and inherent problems of grouping with the example of stroke care].

BACKGROUND AND OBJECTIVES: With the Health Reform 2000, the Australian Refined Diagnosis Related Groups (AR-DRG), Version 4.1 have been chosen as the basis for the future German costing system for hospitals. With regard to Stroke Severity (Barthel Index [BI]) we investigated to what extent the grouping according to AR-DRGs can reproduce healthcare expenditures for such patients. Options to adapt and optimize the system are discussed. PATIENTS AND METHODS: 632 patients who had suffered a cerebrovascular accident and were discharged from conservative acute care in 1999, were classified according to the AR-DRGs. For the grouping we alternatively used data from the current hospital information system and a stroke database for quality assurance. The results were also compared with the clinical profiles for the public hospital sector of the corresponding DRGs in Australia (1997-98). RESULTS: On average 0.99 additional diagnoses per case were documented in the hospital information system, compared to 3.65 in the stroke database. In the stroke database 177 cases (36.8%) were assigned to the DRG with the highest cost weight. 53.7% of these patients suffered a serious stroke (BI < 30). Grouping on the basis of hospital information system data led only to 14 cases (2.8%) assigned to the DRG with the highest cost weight. CONCLUSIONS: Type and extent of additional diagnoses are crucial for the grouping process. From a clinical and economic point of view, measures of disability and impairment should be assigned to the grouping process to improve homogeneity under both aspects. Scores can also serve for determining reliable outcome parameters. For the development of an outcome related reimbursement system, procedures must be included in the definition of medical DRGs. In future, DRGs, which cover overlapping healthcare sectors, should be developed for patients with poststroke rehabilitation.

Australia↗

Sustained improvements in patients with dementia of Alzheimer's type (DAT) 6 months after termination of Cerebrolysin therapy.

The present study is an extension of the work of Rüther et al. (1994). 101 patients suffering from DAT were evaluated 6 months after completion of a 4 week (5 days per week) therapy with either 30 ml Cerebrolysin or placebo. The significant and clinically relevant improvements in the global rating (CGI), clinical symptomatology (SCAG), cognitive performance (ZVT-G) as primary efficacy variables, as well as the improvements in the secondary efficacy variables activities of daily living (NAI) and wellbeing (Bf-S), achieved in the Cerebrolysin group after only 4 weeks of active therapy, were maintained to a large extent during the follow-up period. Although there was a moderate tendency in the drug group towards loss of improvement, the differences between baseline and follow-up examination, as well as the differences between the verum and the placebo group, clearly document a sustained improvement in patients treated with Cerebrolysin in the first 4 weeks of the study period. It can be speculated that relatively short treatment courses with Cerebrolysin in patients suffering from neurodegenerative dementia can lead to long term influence on disease progression, which is in accordance with the proposed neurotrophic - nerve growth factor like - mode of action.

Activities of Daily Living↗

Selective in vivo radiosensitization by 5-fluorocytosine of human colorectal carcinoma cells transduced with the E. coli cytosine deaminase (CD) gene.

PURPOSE: The E. coli cytosine deaminase (CD) gene encodes an enzyme capable of converting the nontoxic prodrug 5-fluorocytosine (5-FC) to 5-fluorouracil (5-FU), a known radiosensitizer. Having previously shown that combined CD suicide gene therapy and radiation (RT) results in pronounced radiosensitization in vitro, we progressed to in vivo studies of combined therapy. METHODS AND MATERIALS: WiDr human colon cancer cells were transduced in vitro with the CD gene and cells expressing CD were selected for use as xenografts in a nude mouse model. After administration of 5-FC, tumors received 10-30 Gy local field radiation (RT) and tumor growth delay was compared to control animals receiving either 5-FU, 5-FC, or RT alone. RESULTS: Maximal growth delay was seen in mice treated with 5-FC for 6 consecutive days prior to RT. Combined treatment with 15 Gy radiation resulted in a dose-modifying factor (DMF) of 1.50, and a greater DMF was observed with higher doses of radiation. There was no appreciable toxicity using this new approach. In contrast, a similar treatment of combined 5-FU and radiation resulted in considerable toxicity and no appreciable radiosensitization. CONCLUSION: The present results show that combined suicide gene therapy and RT results in pronounced antitumor effect without any notable toxicity. This indicates that the CD gene may be useful in the development of novel treatment strategies combining radiation and gene therapy in the treatment of locally advanced cancers.

Animals↗

Efficacy of the peptidergic nootropic drug cerebrolysin in patients with senile dementia of the Alzheimer type (SDAT).

Cerebrolysin is a peptidergic nootropic drug with a multimodal mechanism of action. It is expected to have a positive influence on neurodegenerative diseases such as senile dementia of the Alzheimer type (SDAT). Experimental studies have shown Cerebrolysin to have a regulatory effect on energy metabolism, a positive influence on behavior through neuromodulation due to its peptide fraction, and most important, a neurotrophic stimulation. In SDAT and related disorders the neurotrophic effect of the drug could play a major role and influence the progress of the illness. A placebo-controlled double-blind trial was designed to examine the efficacy of the drug in SDAT. Confirmatory statistics were used for analysis. 120 subjects with mild to moderate dementia according to the Global Deterioration Scale (GDS) were included in the trial. Their performance on the Mini Mental State Examination (MMSE) was between 15 and 25. The diagnosis was substantiated by the Hachinski Ischemic Score and cranial computed tomography. The inclusion and exclusion criteria were formulated so as to prevent a distortion between the two arms by secondary dementia or other disease. The two arms received either placebo or the drug once a day (30 ml Cerebrolysin in 100 ml physiological saline i.v.) from Monday to Friday for four weeks. Physiological saline (130 ml) was used as placebo. Primary variables used for the statistical analysis were the Clinical Global Impression (CGI), which measures the improvement in symptoms, the SCAG score, and the performance in the trial-making test (ZVT-G). The self-assessment in the Bf-S and the activities of daily living in the NAI were used as secondary variables.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Parenteral dipyrone versus diclofenac and placebo in patients with acute lumbago or sciatic pain: randomized observer-blind multicenter study.

Two hundred and sixty patients with lumbago or sciatic pain participated in a multicenter observer-blind randomized trial to compare the efficacy and tolerability of dipyrone 2.5 g, diclofenac 75 mg, and placebo administered as an intramuscular injection once daily for the duration of one to two days. The effectiveness of the test treatments in relieving sciatic pain was measured by a visual analog scale (VAS) before and 30 minutes, 1, 2, 3, 6 and 24 hours after each injection. In addition, the patient's general well-being was measured on a 5-point rating scale on day 0, 1 and 2. At the end of the trial, the patients evaluated the overall efficacy of the study drugs on a 5-point rating scale. Minimal finger-toe distance was measured every day of the trial. Pain intensity on VAS (primary endpoint) showed a significantly greater reduction with dipyrone than with diclofenac or placebo between 1 and 6 hours after application (p < 0.01) and at the end of the trial (after 48 hours). Improvement in general well-being and minimal finger-toe distance was greatest in the dipyrone group. 59% of the patients with dipyrone assessed the overall efficacy as "excellent" or "very good", compared with 30% with diclofenac, and 18% with placebo. Adverse reactions were reported in only 7 patients (3%), 4 (5%) in the dipyrone, 1 (1%) in the diclofenac, and 2 (2%) in the placebo group.

Adult↗

Alloxan and ninhydrin inhibition of hexokinase from pancreatic islets and tumoural insulin-secreting cells.

Alloxan inhibited hexokinase activity in cytoplasmic fractions of transplantable radiation-induced rat islet cell tumours, ob/ob mouse pancreatic islets, rat liver and rat kidney. Half maximal inhibitory concentrations of alloxan were greater than those previously found for half maximal inhibition of pancreatic islet or liver glucokinase. D-glucose, preferentially the alpha-anomer, and D-mannose protected hexokinase activity against alloxan inhibition. 1,4-Dithiothreitol completely protected against and partially reversed the alloxan inhibition of hexokinase. The ability of various dithiols to reverse the inhibition of hexokinase by alloxan was dependent on the spacing between the SH (thiol) groups. Only dithiols with intermediate spacing between the SH groups were effective. Dithiols with two vicinal SH groups such as 1,2-dimercaptoethane and 2,3-dimercaptopropanol (BAL) and dithiols with more widely spaced SH groups such as 1,5-dimercaptopentane were ineffective. Thus a reaction of alloxan with two SH groups in the sugar binding site of the hexokinase with the formation of a disulfide bond may be involved in the reversible inhibition of the enzyme. Ninhydrin also inhibited hexokinase from all four tissues studied. The half maximal inhibitory concentrations of ninhydrin were lower than those of alloxan. Inhibition of hexokinase may be an important factor in the general cytotoxic action of ninhydrin. However, inhibition of pancreatic islet hexokinase is unlikely to be the initial event in the pancreatic B-cell toxic action of alloxan, even if inhibition of hexokinase by high concentrations of alloxan may contribute to the B-cell toxic action.(ABSTRACT TRUNCATED AT 250 WORDS)

Alloxan↗

[Treatment of acne with a yeast preparation].

In a randomized, controlled double-blind study involving 139 patients with various forms of acne, the effectiveness and tolerance of Saccharomyces cerevisiae Hansen CBS 5926 (Perenterol) was studied in comparison with a placebo over a maximum period of five months. The results of therapy were assessed by the physician as very good/good in 74.3% of the patients receiving the preparation, as compared with 21.7% in the placebo group. In more than 80% of the former patients, the condition was considered to be healed or considerably improved, while the corresponding figure for the placebo group was only 26%. Seasonal differences in the effect of treatment with Saccharomyces cerevisiae Hansen CBS 5926 were not observed. Side effects leading to a premature discontinuation of the test were seen neither in the test substance group nor in that receiving placebo. The therapeutic efficacy of Saccharomyces cerevisiae Hansen CBS 5926 makes this systemic form of therapy an alternative that is becoming more and more widely accepted by acne patients.

Acne Vulgaris↗

Inhibition of glucokinase by alloxan through interaction with SH groups in the sugar-binding site of the enzyme.

Alloxan is known to inhibit pancreatic B cell and liver glucokinase and glucose protects the enzyme against inhibition. The dithiol 1,4-dithiothreitol (1,4-DTT) protected against and reversed the inhibition of glucokinase by alloxan. An investigation into the structure-activity relationship using a variety of different dithiols demonstrated that the ability of the dithiols to protect against and to reverse the inhibition of glucokinase by alloxan was dependent on the spacing between the SH (thiol) groups of the various dithiols. Only 1,3-dimercaptopropane, 1,4-dimercaptobutane, 1,4-dithioerythritol, and 1,4-DTT, with intermediate spacing between the SH groups, reversed the inhibition of glucokinase induced by alloxan. Dithiols with two vicinal SH groups such as 1,2-dimercaptoethane and 2,3-dimercaptopropanol (BAL) were ineffective in the same way as dithiols with more widely spaced SH groups such as 1,5-dimercaptopentane and 1,6-dimercaptohexane. Except for 1,6-dimercaptohexane, all dithiols also protected glucokinase against the inhibition of alloxan. The monothiol cysteine, but not glutathione, a tripeptide monothiol, also protected glucokinase against alloxan inhibition but both were unable to reverse the inhibition. Like alloxan, other dithiol reagents such as ninhydrin, N-ethylmaleimide, and maleimide inhibited glucokinase. Glucose and 1,4-DTT protected glucokinase against this inhibition. 1,4-DTT partially reversed this inhibition. It is concluded, therefore, that the mechanism of inhibition of glucokinase by alloxan is a reaction of alloxan with two adjacent SH groups in the depth of the sugar-binding site of the glucokinase, with formation of a disulfide bond and concomitant inactivation of the enzyme. Because glucokinase can couple changes in the blood glucose concentration to changes in the glycolytic flux rate and corresponding changes in the rate of insulin secretion, it may function as a glucose signal recognition enzyme in the pancreatic B cell. This mechanism of interaction of alloxan with glucokinase may thereby provide an explanation for the ability of alloxan to inhibit glucose-induced insulin secretion.

Alloxan↗