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Biomedical subjects

M Frank

Publications and source records attributed to M Frank.

At least 55 records · Page 3Linked to original sources
PubMed2000

Prandial glucose regulation with repaglinide: its clinical and lifestyle impact in a large cohort of patients with Type 2 diabetes.

OBJECTIVE: Prandial glucose regulation has the potential for achieving good metabolic control with a low risk of hypoglycaemia and increased flexibility with regard to eating patterns. Comparative studies have suggested that the prandial glucose regulator repaglinide is at least equivalent to sulphonylureas in terms of efficacy, but incurs a lower risk of major hypoglycaemia. However, these trials employed fixed dosing and mealtime regimens, so repaglinide was not used as intended. This prospective investigation in a daily clinical setting aimed to assess the efficacy and tolerability profile of flexible prandial glucose regulation with repaglinide in Type 2 diabetes. DESIGN: 5,985 patients with Type 2 diabetes in Germany were surveyed prospectively. These patients were assessed before and after a mean of 46 days treatment with repaglinide. At baseline, available data showed that 64% of patients had previously received therapy with conventional oral antidiabetic drugs, 22% were on diet alone, and 13% were naive to any treatment. RESULTS: Overall, mean HbA1c decreased from 8.6 to 7.4%, fasting blood glucose from 183.9 to 134.2 mg/dl (10.2 to 7.4 mmol/l), blood glucose prior to main meals from 198.5 to 141.4 mg/dl (11 to 7.8 mmol/l), and blood glucose 2 hours after main meals from 219.3 mg/dl to 153.2 mg/dl (12.2 to 8.5 mmol/l). Subgroup analysis showed significant improvements in each of these parameters (P<0.0001) in therapy-naive patients, in patients switched from other oral antidiabetic drugs, and in patients receiving repaglinide as combination therapy. Body weight decreased slightly (1.2+/-2.7 kg). Only 49 hypoglycaemic episodes were reported, of which 38 cases were mild and no adverse sequelae to these events have been reported. Repaglinide also led to a liberating effect on lifestyle when patients were switched from other oral hypoglycaemic agents (OHAs), with 80% reporting a sense of relief at the prospect of being able to miss meals. The proportion of these patients reporting lifestyle restrictions as a result of fixed mealtimes declined from 36% to 7%. Before switching, 38% of the patients admitted to eating when not hungry for fear of hypoglycaemia, but only 10% continued this behaviour and patients took fewer supplementary snacks after switching to repaglinide. CONCLUSION: Prandial glucose regulation with repaglinide improves metabolic control in patients with Type 2 diabetes without causing weight gain and with few hypoglycaemic episodes. This beneficial effect is seen in patients who are therapy-naive, have switched from alternative OHAs, or are in need of combination therapy. The prandial approach to treatment has a liberating effect with regard to eating behaviour that is welcomed by most patients switched from alternative therapies.

Attitude to Health↗
PubMed2000

Progressive segregation of unmyelinated axons in peripheral nerves, myelin alterations in the CNS, and cyst formation in the kidneys of myelin and lymphocyte protein-overexpressing mice.

Myelin and lymphocyte protein (MAL) is a putative tetraspan proteolipid that is highly expressed by Schwann cells and oligodendrocytes as a component of compact myelin. Outside of the nervous system, MAL is found in apical membranes of epithelial cells, mainly in the kidney and stomach. Because MAL is associated with glycosphingolipids, it is thought to be involved in the organization, transport, and maintenance of glycosphingolipid-enriched membrane microdomains. In this report, we describe the generation and analysis of transgenic mice with increased MAL gene dosage. Immunohistochemical analysis revealed that the localization of MAL overexpression in the transgenic animals corresponded closely to the MAL expression pattern observed in wildtype animals, indicating correct spatial regulation of the transgene. Phenotypically, MAL overexpression led to progressive dissociation of unmyelinated axons from bundles in the PNS, a tendency to hypomyelination and aberrant myelin formation in the CNS, and the formation of large cysts in the tubular region of the kidney. Thus, increased expression of MAL appears to be deleterious to membranous structures in the affected tissues, indicating a requirement for tight control of endogenous MAL expression in Schwann cells, oligodendrocytes, and kidney epithelial cells.

Abnormalities, Multiple↗
PubMed2000

[Pattern of injuries and risk of injury in skateboarding].

After the first big wave in the late seventies skateboarding is facing a revival as a leisure sport nowadays. 63 Skateboarders with a mean age of 18.1 years were personally interview with a survey form. 148 injuries with a resulting sport break of at least one week were registered. Sprains (36.5%), bruises (24.3%), fractures (18.2%) and lacerations of the skin (12.8%) were the most common injuries. 86.5% were injuries of the extremities almost equally distributed among the upper and lower limbs. Most fractures happened to the upper limbs (81.5%) mainly distal of the elbow joint. Sprains were mainly located at the lower limbs (70.4%) especially at the ankle joint as the most vulnerable part of the body (26.4% of all injuries). 101 injuries (68.2%) were treated by physicians. The resulting risk of injury was one injury per athlete and 1000 hours of exposure time. A higher acceptance of prophylactic measures could minimize the risk of injury. Parallels to inline skating and snowboarding can be shown.

Adolescent↗
PubMed2000

Hormone autotrophic growth and differentiation identifies mutant lines of Arabidopsis with altered cytokinin and auxin content or signaling.

We describe mutant tissue lines of Arabidopsis that are able to grow in vitro as callus on hormone-free medium. The 14 lines presented here show different hormone autotrophic differentiation behaviors that can be classified into three categories: (a) forming roots (rooty callus), (b) forming shoots or shoot-like structures (shooty callus), or (c) growing without organ formation (callus). Three fast-growing lines showed altered steady-state mRNA levels of the Cdc2 and CycD3 cell cycle genes. Three of the six rooty callus lines contained about 20- to 30-fold higher levels of auxins than wild-type callus. These and two other lines with normal auxin content showed an increased steady-state level of IAA1 and IAA2 transcripts in the absence of exogenous auxin. Five of the six shooty callus lines had increased steady-state mRNA levels of the CKI1 gene and/or of the homeobox genes KNAT1 and STM, suggesting that the phenotype is linked to altered cytokinin signaling. Also, one cytokinin-overproducing line with only 5% of wild-type cytokinin oxidase activity was identified. These results indicate that screening for hormone-autonomous growth identifies mutants with altered hormone content or signaling.

Arabidopsis↗
PubMed2000

Efficacy and cardiac safety of propiverine in elderly patients - a double-blind, placebo-controlled clinical study.

The study investigated the efficacy and cardiac safety of propiverine in the elderly, because the induction of life-threatening ventricular arrhythmia has been reported for some drugs prescribed in the therapy of urinary incontinence. Ninety-eight patients (21 male, 77 female; 67.7+/-6.3 years of age) suffering from urgency, urge incontinence or mixed urge-stress incontinence were included in the double-blind, multicentre, placebo-controlled, randomized study. After a 2-week placebo run-in period, the patients received propiverine (15 mg t.i.d.) or placebo (t.i.d.) for 4 weeks. Before (V1, V2) and during the treatment period (V3, V4), standard ECGs and 24-hour long-term ECGs were recorded. Propiverine caused a significant reduction of the micturition frequency (V2: 8.7+/-4.2, V4: 6.5+/-3.2 ml; p< or =0.01), reflected in a significant increase in the average micturition volume (V2: 163.5+/-65.9, V4: 216.3+/-101.5 ml; p< or =0.01) and a significant decrease in episodes of incontinence (-54%; p = 0.048). These findings were confirmed by the overall assessment at V4, in which approximately 90% of patients under propiverine either had no urge incontinence or urge symptoms, or showed improvement. Resting and ambulatory electrocardiograms indicated no significant changes. Neither the frequency-corrected Q-T interval nor other cardiac parameters were relevantly altered. The frequency of cardiac events (Lown classes IVa/b) was random, revealing no difference between placebo and propiverine. The incidence of adverse events was very low (2% dryness of the mouth under propiverine) and confirmed by the findings from the quality of life questionnaires. A favourable benefit-risk ratio without the induction of any cardiac arrhythmia in the treatment of elderly patients suffering from urgency, urge incontinence or combined urge-stress incontinence is therefore proven for propiverine.

Age Factors↗
PubMed2000

[Retrospective analysis of dose intensity of epirubicin in breast cancer].

OBJECTIVE: In breast cancer the efficacy of epirubicin-based chemotherapy is possibly related to the actual dose intensity applied. We retrospectively determined the administered dose intensity and the relative toxicity and efficacy of an epirubicin-containing regimen in patients with primary or metastatic breast cancer. PATIENTS AND METHODS: Fluorouracil, epirubicin, and cyclophosphamide (FEC) were either given at a standard dose of 500/50/500 mg/m2 (FE50C) or at an intensified dose of 500/75/500 mg/m2 (FE75C) every 3 weeks. Of the 66 patients treated, 63 were evaluable; 43 had metastatic breast cancer, and 20 patients with an increased risk of relapse received FEC as an adjuvant treatment. RESULTS: Dose intensity and absolute dose of adjuvant treatment were 81 and 70% for FE50C and 96 and 88% for FE75C. In metastatic breast cancer, the dose intensity for FE50C was 94% and for FE75C 92%. In a retrospective comparison, the 4-year overall survival following adjuvant FE50C and FE75C was 40 and 48%, respectively (p = 0.47). The dose intensification led to a higher response rate of 34 vs. 44%. There were no significant differences in response duration and survival time. The toxicity profiles were comparable between FE50C and FE75C. CONCLUSIONS: In general, the doses applied were lower than initially planned. Higher doses of epirubicin did not result in a significant increase of toxicity. Despite the limitations of a retrospective analysis, our observations support the importance of adherence to the planned dose intensity as a prerequisite for optimal treatment of patients suffering from breast cancer. As our results could be related to selection bias, dose-intensified anthracycline-containing regimens should be further evaluated in prospective trials.

Adult↗
PubMed2000

On the sweetness of N-(trifluoroacetyl)aspartame.

A panel of tasters has found that the N-trifluoroacetyl derivative of aspartame is five times less sweet than the parent compound, contrary to the tenet in the literature, but consistent with sweet receptor models which require this nitrogen to exist in protonated form.

Aspartame↗
PubMed2000

Alcian blue pyridine variant--a superior alternative to alcian blue 8GX: staining performance and stability.

We compared the staining performance, dye content, solubility, and visual absorption maximum of two batches of alcian blue pyridine variant and of five batches of alcian blue 8GX (C.I. 74240). Whenever possible, we also compared results to those obtained with the same dye batches produced at an earlier date to provide information concerning dye stability. Both alcian blue pyridine variant batches were of high dye content, stable, of satisfactory solubility, and performed well in both the routine Mowry mucin stain and in the critical electrolyte concentration (CEC) stain. Of the five alcian blue 8GX samples, some were also of appropriate dye content, were sufficiently stable, and gave good staining in the two procedures. Two batches, however, were unstable, and three batches were unsatisfactory in staining performance and solubility in the CEC stain. Consequently alcian blue pyridine variant is a superior substitute for alcian blue 8GX.

Alcian Blue↗
PubMed1999

[Combined anesthesia procedures].

The additive properties of general and regional anesthetic techniques are brought together in combined anesthesia to minimise side effects of the individual techniques. Despite a wide experience with both used as single anesthetic techniques, no definite recommendations regarding indications, general contraindications and procedure exist for their combination. Beneficial effects on haemodynamics, respiratory function, intestinal motility and postoperative stress response have been demonstrated for a combination of general anesthesia and thoracic epidural anesthesia (TEA). In addition TEA is favourable in the management of postoperative pain, which has advantageous effects on convalescence especially in a high risk patient group. Nevertheless, until now no reduction of perioperative morbidity and mortality has been demonstrated. Since the combination of two anesthesia techniques theoretically increases the rate of complication, the expected benefit for the patient must predominate. To estimate the risks and benefits of combined anesthesia, the anesthesiologist must be familiar with each single method, as well as with the synergistic effects of both techniques in order to evaluate the individual indication.

Anesthesia, Conduction↗
PubMed1999

Increased steady state mRNA levels of the STM and KNAT1 homeobox genes in cytokinin overproducing Arabidopsis thaliana indicate a role for cytokinins in the shoot apical meristem.

This study investigates the consequences of endogenously enhanced biosynthesis of the plant hormone cytokinin in Arabidopsis thaliana (L.) Heynh. Transcriptional control of the bacterial ipt gene by the Drosophila melanogaster hsp70 promoter enabled temperature-dependent increased cytokinin production in transgenic plants. Heat-treated plants accumulated higher levels of unbound and bound zeatin-type cyto-kinins, the latter being preferentially N-conjugated glucosides. Cytokinin overproduction significantly increased the biomass of seedlings. Ipt transgenics had higher steady state mRNA levels of the shoot meristem specifying homeobox genes KNAT1 and STM, similar to the cytokinin-overproducing shoot meristem mutant amp1 (hpt, cop2, pt) This finding, together with previously described phenotypic similarities between transgenic cytokinin-overproducing plants and plants overexpressing the KNAT1 or KN1 genes, suggests that these factors act on the same pathway. We hypothesize that cytokinins act upstream of KNAT1 and STM. The influence of cytokinins on homeobox genes provides a link between the hormone and the developmental genes and indicates a role for cytokinins in the shoot apical meristem.

Alkyl and Aryl Transferases↗
PubMed1999

Developmental expression pattern of the myelin proteolipid MAL indicates different functions of MAL for immature Schwann cells and in a late step of CNS myelinogenesis.

The myelin and lymphocyte protein MAL is a small proteolipid of 17 kDa and is expressed by oligodendrocytes and Schwann cells. We have characterized the embryonic and postnatal expression of MAL in the rat nervous system by in situ hybridization, immunocytochemistry, and western blotting and compared it with that of other myelin constituents. In the CNS, MAL is expressed during late steps of myelination: MAL protein appears approximately 3-5 days later than myelin basic protein and proteolipid protein. In contrast, in the PNS, MAL transcript and protein expression is detected prior to the onset of myelination, as early as embryonic day 17. Our results demonstrate that MAL is differentially expressed in oligodendrocytes and Schwann cells, likely reflecting different functions of the MAL proteolipid: (1) The late expression of MAL protein in the CNS points to a role in the final steps of myelin sheath formation, such as stabilization of the compacted myelin membranes. (2) The early expression of MAL protein in immature Schwann cells suggests an important role of MAL in the terminal differentiation step of the Schwann cell lineage and in the onset of peripheral myelination.

Animals↗
PubMed1999

Combination therapy with octreotide and alpha-interferon: effect on tumor growth in metastatic endocrine gastroenteropancreatic tumors.

OBJECTIVE: We investigated the antiproliferative efficacy of the addition of alpha-interferon to the somatostatin analogue octreotide in patients with metastasized gastroenteropancreatic tumors unresponsive to octreotide monotherapy. METHODS: In an open prospective trial, 21 patients with metastasized neuroendocrine gastroenteropancreatic tumors (nine patients with carcinoid syndrome, eight with nonfunctioning tumors, four with gastrinoma) were treated with 5 x 10(6) IU alpha-interferon tiw in addition to 200 microg of octreotide tid. All patients, including 16 patients with preceding monotherapy with 200 microg of octreotide tid, had tumor progression documented by computed tomography before entering the study. Growth response (computed tomography documented) and biochemical response were assessed at 3-month intervals. RESULTS: Inhibition of tumor growth was observed in 14 patients (67%), 11 of whom had preceding octreotide monotherapy; complete regression was observed in one patient lasting for 49 months and stable disease (stand-still) in 13 patients lasting for 3 to 52 months (median, 12 months). Seven patients failing this combination therapy exhibited a significantly shorter overall survival (median, 23 months; range, 5 to 42 months) than the 14 patients responding to this regimen (median, 68 months; range, 12 to 112 months; p = 0.007). Two patients are still alive. Biochemical response was achieved in 69% of patients with functioning tumors: in three of four patients with gastrinoma and in six of nine patients with carcinoid syndrome. CONCLUSIONS: These data suggest that the addition of alpha-interferon to octreotide has antiproliferative efficacy in a subgroup of patients with advanced metastatic disease unresponsive to octreotide monotherapy. Prolonged survival was seen in the responder group.

Adult↗
PubMed1999

[Mother-child treatment. Chance for differentiated and specific introduction of necessary psychological preventative and treatment measures].

Many women are often caught up in multi-layered situations of stress and strain without having an opportunity to speak about themselves and their difficulties. Within the setting of a health recovery programme for mothers and their child(ren), a first step might be possible to raise their awareness for an underlying psychological problem. Interventions might focus on symptoms pertaining to the psychological, psychosomatic and psychosocial sphere. Experience shows that the clients mostly present with problems specific to women. Describing various interventions, the author discusses psychological support measures that might be provided for women in the course of a health recovery programme.

Adult↗