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Biomedical subjects

R Thiel

Publications and source records attributed to R Thiel.

At least 19 recordsLinked to original sources

Might calcium disorders cause or contribute to myoclonic seizures in epileptics?

Although epilepsy is not rare, many epileptic conditions are considered to be idiopathic and the related seizures of unknown origin. It does appear that different types of seizures are caused by differing mechanisms. This paper discusses scattered case reports involving problems with calcium metabolism and the thyroid, and/or the parathyroid glands concurrent with seizures that support the position that calcium control mechanisms may have been involved in causing seizures in those patients. This paper hypothesizes that calcium levels can cause, or at least contribute to myoclonic (jerk) seizures, as well as to possibly infantile spasms. As these conditions are difficult to treat medically, this paper suggests that nutritional interventions, such as supplemental calcium, magnesium and/or vitamin D, might well be considered as an option as a first-line treatment in those with these types of epileptic disorders. The nutritional recommendations also would apply for those who have seizures concurrent with Down syndrome.

Calcium↗

[Clinical pathways. Implementation in a urological department].

BACKGROUND: Clinical pathways are directions for standardised treatment processes for different diseases or procedures in a hospital. These pathways are developed within a team of several professions and are used as order and procedure sheets. Experiences with this element of quality management are limited in Germany. METHODS: The development and the implementation process of 15 pathways in a urological department are described. A clinical pathway for female incontinence surgery (suburethral tape) is presented as an example. The effects of the pathways are evaluated on a routine basis. RESULTS: Seventy-two percent of the patients were treated according to a clinical pathway. The advantages of clinical pathways are a better structuring and transparency of medical processes, a reduction of documentation, improvements in medical education and savings in time, hospital stay of the patients and costs. Expenses for pharmaceuticals were significantly reduced in connection with development of the pathways. CONCLUSIONS: The implementation of clinical pathways is a complex but rewarding project. It can be expected that clinical pathways will be rapidly distributed in the near future and that they will contribute to improvements of health care quality.

Critical Pathways↗

[Female sexual function before and after treatment of urinary incontinence].

The prevalence of urinary incontinence is around 20% of healthy middle-aged women. Incontinence causes a negative impact on the quality of life and sexuality. From August 2002 to January 2004, 30 patients (mean age 43 years) with stress urinary incontinence (59%), overactive bladder (15%) and mixed incontinence (26%) answered the ICIQ-SF(International Consultation on Incontinence Questionnarie-Short Form) and FSFI (Female Sexual Function Index) questionnaires before and after treatment for urinary incontinence. The follow-up ranged from 12 to 53 months. Mean ICIQ score was 17 and 7 before and after treatment respectivelly (p<0,001). Overactive bladder showed the worst scores in all domains. The patients who underwent surgery increased their scores of desire (p=0,02), satisfaction (p=0,05) and total score (p=0,02). Thirteen patients which ICIQ was zero increased: desire (p<0,01), satisfaction (p=0,05) and total score (p=0,01). Urinary incontinence significantly affects the quality of life. Therefore sexual evaluation in incontinence patients is recommended.

Adult↗

An improved method for the automated enumeration of fluorescently labelled bacteria in human faeces.

The study aimed to improve microscopy-based automated recognition of faecal bacterial cells labelled with 16S rRNA-targeted oligonucleotides and 4',6-diamidino-2-phenylindole (DAPI). Based on the software KS400 (Carl Zeiss Vision, Hallbergmoos, Germany), designed for automising microscopy-based image capture and image analysis, a routine was developed that affords the recognition of doubly stained bacteria and the rejection of artefacts. The accuracy of the automated enumeration was investigated by comparing the resulting data with those obtained by manual counting. The newly developed method was subsequently used to compare the total bacterial counts in human faecal samples using the domain specific probe Eub338 alone and a mixture of 5 domain-specific probes, respectively. Faecal samples from 90 healthy volunteers were analysed. The cell counts obtained with Eub338 were 10% lower than those obtained with the probe mixture. Since the cells detected with the probe mixture covered a wide range of signal intensities, a dynamic analysis routine was developed to effectively detect the whole range of bright to weak signals within the same image, while at the same time reliably rejecting artefacts.

Automation↗

Can cognitive deterioration associated with Down syndrome be reduced?

Individuals with Down syndrome have signs of possible brain damage prior to birth. In addition to slowed and reduced mental development, they are much more likely to have cognitive deterioration and develop dementia at an earlier age than individuals without Down syndrome. Some of the cognitive impairments are likely due to post-natal hydrogen peroxide-mediated oxidative stress caused by overexpression of the superoxide dismutase (SOD-1) gene, which is located on the triplicated 21st chromosome and known to be 50% overexpressed. However, some of this disability may also be due to early accumulation of advanced protein glycation end-products, which may play an adverse role in prenatal and postnatal brain development. This paper suggests that essential nutrients such as folate, vitamin B6, vitamin C, vitamin E, selenium, and zinc, as well as alpha-lipoic acid and carnosine may possibly be partially preventive. Acetyl-L-carnitine, aminoguanidine, cysteine, and N-acetylcysteine are also discussed, but have possible safety concerns for this population. This paper hypothesizes that nutritional factors begun prenatally, in early infancy, or later may prevent or delay the onset of dementia in the Down syndrome population. Further examination of these data may provide insights into nutritional, metabolic and pharmacological treatments for dementias of many kinds. As the Down syndrome population may be the largest identifiable group at increased risk for developing dementia, clinical research to verify the possible validity of the prophylactic use of anti-glycation nutrients should be performed. Such research might also help those with glycation complications associated with diabetes or Alzheimer's.

Cognition Disorders↗

Serum HER2 extracellular domain in metastatic breast cancer patients treated with weekly trastuzumab and paclitaxel: association with HER2 status by immunohistochemistry and fluorescence in situ hybridization and with response rate.

PURPOSE: We explored the relationship between circulating HER2 extracellular domain (ECD) and tissue HER2 status as determined by immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH). We also examined its predictive value in a cohort of metastatic breast cancer patients treated with weekly trastuzumab and paclitaxel. METHODS: Eligible patients had pre- and post-treatment stored serum specimens and were treated on a previously reported phase II trial. Retrospective analysis evaluated: the association between pretreatment serum HER2 ECD and tissue HER2 status by IHC and FISH; and the association between change in serum HER2 ECD after 12 weeks of therapy and response proportion. RESULTS: Stored serum samples were available for 55/95 (58%) patients. Statistically significant associations were found between HER2 status as assessed by IHC and FISH, and baseline serum HER2 ECD level. Patients whose ECD normalized after 12 weeks of therapy had a higher response proportion compared with patients with persistently high ECD levels (68% versus 15%, P=0.005). A relative decline of over 55% from baseline HER2 ECD predicted response to therapy. CONCLUSION: A statistically significant association was observed between pretreatment serum HER2 ECD and tissue HER2 status as assessed by IHC and FISH. A decrease in serum HER2 ECD level was a significant predictor of response to trastuzumab-based therapy.

Adult↗

[The radical retropubic prostatectomy -- gold standard for prostate cancer?].

Radical retropubic prostatectomy is still the most frequent surgical procedure for the treatment of localized prostate cancer. Improvements in the surgical techniques have contributed to significant reduction in operative time (median 69 min) and in rates of early and late complications. The surgical procedure and perioperative management are described, and results in 180 consecutive cases are presented. Severe postoperative complications did not occur. More than 95% of patients were completely dry within 6 months. Erectile function recovered in 71% of patients with bilateral preservation of the neurovascular bundles and in 34% of patients with unilateral nerve sparing. These results are in good agreement with data from the literature and confirm the outstanding role of the retropubic approach as the gold standard for radical prostatectomy, as well as the reproducibility of the result in community-based hospitals.

Adult↗

[The transobturator tape (TOT). A minimally-invasive procedure for the treatment of female urinary stress incontinence].

The transobturator tape, a new technique for the treatment of female urinary stress incontinence, was evaluated with a 1 year follow-up.A total of 124 patients were treated with a low elasticity polypropylene tape according to the technique described by Delorme. The operative procedure is described step by step. All patients were followed-up after 3, 6 and 12 months. No intra-operative complications were observed. After 12 months 88.7% of the patients were cured and an additional 6.4% showed improvement. The transobturator technique (from exterior to interior) is, given proven indications and an exact consideration of the instructions, a simple, safe and efficient surgical procedure for the treatment of female urinary stress incontinence. The technique avoids complications such as bladder, intestinal and vascular lesions. It is suitable for genuine incontinence and patients with recurrent stress incontinence.

Adult↗

Synthesis, high-performance liquid chromatography-nuclear magnetic resonance characterization and pharmacokinetics in mice of CD271 glucuronide.

Retinoic acid-glucuronides are known as retinoids with activity in acne therapy, limited placental transfer and reduced retinoid adverse effects. We synthesized the glucuronide of a novel retinoid, CD271 (adapalene), used for the treatment of moderate acne. The synthesis product ("CD271 glucuronide", CD271G) was purified by preparative HPLC. It undergoes in aqueous solution, like other glucuronides, rapid acyl-migration of the bound aglycone leading to position isomers. Thus characterization of purified CD271G could be only achieved by HPLC-NMR coupling. A subfraction ("CD271GB") consisting essentially of 2'- and 3'-CD271G was used for pharmacokinetic studies. After a single subcutaneous injection at a dosage of 30 mg/kg the substance showed considerable uptake and metabolism to CD271 indicating that CD271GB could serve as a prodrug for CD271.

Adapalene↗

Assessment of P450 induction in the marmoset monkey using targeted anti-peptide antibodies.

The identity and expression of hepatic P450 enzymes in marmosets was investigated using a panel of anti-peptide antibodies originally targeted against human P450 enzymes. In immunoblotting, of 12 antibodies examined, 10 bound specifically to bands in marmoset liver microsomal fraction corresponding to P450 enzymes. It is proposed that these represent marmoset CYP1A1, CYP1A2, CYP2A, CYP2B, CYP2C forms (CYP2C-1 and CYP2C-2), CYP2D19, CYP3A21 and another CYP3A form (CYP3A-m). The antibodies, together with an anti-marmoset CYP2E1 antibody, were used to investigate the expression of 10 P450 enzymes in marmosets treated with P450-inducing chemicals. Treatment with phenobarbitone caused CYP2B, CYP2C-2 and CYP3A21 levels to increase, rifampicin caused increases in CYP2B and CYP2C-1 and a decrease in CYP3A21 levels, whereas dioxin caused CYP1A1 and CYP1A2 levels to increase and CYP2E1 levels to decrease. Clofibric acid did not induce any P450. P450 enzyme activities were assessed using 8 different substrates and increases were found after treatment with phenobarbitone, rifampicin, and dioxin. However, due to species differences in substrate selectivity, it proved difficult to ascribe these changes to individual P450 enzymes. Thus, the use of anti-peptide antibodies provides a more informative way of assessing the levels of specific P450 enzymes than enzyme activity measurements.

Amino Acid Sequence↗

[Postobstructive polyuria in unilateral hydronephrosis. A case with 58 l/day].

Increased urinary outputs are common after release of bilateral ureteral or subvesical obstruction. However, polyuria is rare following unilateral obstruction. We report a case of excessive postobstructive diuresis of more than 58,000 ml per day (204 l in 10 days) after release of a left ureteral obstruction in a 56-year-old female, being the highest amounts reported in the literature. Polyuria was derived from the obstructed as well as from the normal contralateral kidney. The involved pathomechanism is complex and not completely understood. Treatment includes careful monitoring of the patient and replacement of fluid and electrolytes. In our case complete recovery of kidney function was observed after several days.

Female↗

Effects of fluoroquinolones on the locomotor activity in rats.

During therapy with fluoroquinolones adverse CNS reactions such as dizziness, light-headedness, insomnia or sleepiness are observed in up to 20% of patients. Using a device developed at our institute for the simultaneous registration of the activity of rats housed in single cages, we have investigated the effects of trovafloxacin, fleroxacin or ofloxacin on the locomotor activity of juvenile and adult rats (11 per group) after oral administration of 600 mg/kg for 5 consecutive days. The effects were most pronounced after fleroxacin, which induced a reduction in activity to 36 +/- 9% (mean +/- SD) of the values measured in juvenile rats before treatment and to 60 +/- 21% (mean +/- SD) in adult rats. HPLC analysis of the plasma concentrations in juvenile rats showed that the concentrations of trovafloxacin were considerably lower than those of the other fluoroquinolones that had been studied previously in our laboratory: the peak concentration of trovafloxacin was 14 +/- 2.9 mg/l (mean +/- SD) after a single dose of 600 mg/kg in juvenile rats. Overall, we showed that the locomotor activities of juvenile and adult rats were significantly depressed during treatment with fluoroquinolones. The effects were more pronounced in juveniles. Monitoring of the locomotor activity of rats is a suitable approach to study CNS effects of fluoroquinolones in animals, but pharmacokinetics have to be taken into account.

Administration, Oral↗

Expression of adhesion receptors on rat limb bud cells and results of treatment with a thalidomide derivative.

The expression of several adhesion surface receptors was studied on cells of early limb bud development of 58 Wistar rats treated orally with two daily doses of the thalidomide derivative EM12 (2 x 50 mg/kg body weight) from day 7 to 10 of pregnancy. EM12 is a more potent teratogen than thalidomide. Limb bud cells of 56 untreated animals served as controls. The studies revealed that the integrins CD11a, CD11b, CD18, CD49d, and CD61, as well as the additional adhesion receptors CD54, CD62L, and the transferrin receptor CD71 were expressed on day 11 of gestation to various degrees on these embryonic cells. In contrast to results of previous studies with a non-human primate (Callithrix jacchus) there was no down-regulation of any of these receptors on the surface of limb bud cells of the rat embryos after treatment with EM12. This result is in accordance with the lack of teratogenicity in this rodent species.

Animals↗

Incorporation of 1-[1-(13)C]Deoxy-D-xylulose in chamomile sesquiterpenes.

Incorporation of synthetically prepared 1-[1-(13)C]deoxy-d-xylulose into chamomile sesquiterpenes has been achieved by injecting an aqueous solution into the anthodia of the plant. The analysis of labeling patterns and absolute (13)C abundances of the isolated sesquiterpenes bisabololoxide A (1), bisabololoxide B (2), and chamazulene (3) using quantitative (13)C NMR spectroscopy showed that 1-[1-(13)C]deoxy-d-xylulose was efficiently incorporated in all three isoprene building blocks of the sesquiterpenes. A significantly lower (13)C abundance of the labeled carbon atom in the biogenetically terminal isoprene unit confirms the mixed biosynthesis of this unit, involving both the mevalonic acid pathway and the methylerythritol phosphate pathway.

Carbon Isotopes↗

Involvement of the mevalonic acid pathway and the glyceraldehyde-pyruvate pathway in terpenoid biosynthesis of the liverworts Ricciocarpos natans and Conocephalum conicum.

The incorporation of 13C-labeled glucose into borneol, bornyl acetate, the sesquiterpenes cubebanol and ricciocarpin A, phytol, and stigmasterol has been studied in axenic cultures of the liverworts Ricciocarpos natans and Conocephalum conicum. Quantitative 13C NMR spectroscopic analysis of the resulting labeling patterns showed that the isoprene building blocks of the sesquiterpenes and stigmasterol are built up via the mevalonic acid pathway, whereas the isoprene units of the monoterpenes and the diterpene phytol are exclusively derived from the glyceraldehyde-pyruvate pathway. These results indicate the involvement of both isopentenyl diphosphate biosynthetic pathways in different cellular compartments.

Camphanes↗

Identification of CYP2E1 in marmoset monkey.

CYP2E1 is the main enzyme responsible for chlorzoxazone 6-hydroxylase activity in human liver. Here, it is shown that marmoset monkey liver microsomal fraction catalyses this reaction at a similar rate and with a similar Km to human liver and that the activity is increased 4-fold in marmosets treated with isoniazid, a known inducer of CYP2E1. This indicates that CYP2E1 is present in marmoset liver. However conversely, an anti-peptide antibody targeted against the C-terminus of human and cynomolgus monkey CYP2E1 (Val-Ile-Pro-Arg-Ser) failed to bind to marmoset monkey hepatic microsomal fraction. To investigate if there is a difference in the C-terminus of CYP2E1 in these species, this region of marmoset CYP2E1 was sequenced following amplification of marmoset liver cDNA with primers selected according to conserved regions identified in human and cynomolgus monkey CYP2E1. It was found that the deduced amino acid sequence of marmoset CYP2E1 in this region is very similar to human CYP2E1, but due to two base differences in the marmoset nucleic acid sequence, the C-terminus of marmoset CYP2E1 is extended by 2 amino acids, i.e. Val-Ile-Pro-Arg-Ser-Ser-Val. This difference is sufficient to prevent the binding of an antibody raised against the C-terminus of human CYP2E1. The expression of CYP2E1 in the marmoset was confirmed by raising an antibody against the deduced C-terminus of marmoset CYP2E1 (Pro-Arg-Ser-Ser-Val). In immunoblotting, this antibody bound to a single protein of 54 kDa in marmoset liver microsomal fraction. The intensity of the band was increased in isoniazid-treated marmosets, consistent with induction of CYP2E1. The antibody did not recognise human or cynomolgus monkey CYP2E1. This was expected since the immunising peptide sequence does not occur in these enzymes. The results demonstrate the presence of CYP2E1 in marmoset liver and illustrate the importance of the C-terminus for the production of specific antibodies against P450 enzymes.

Amino Acid Sequence↗

Idiopathic partial thrombosis of the corpus cavernosum.

A case of spontaneous, partial, unilateral thrombosis of the corpus cavernosum is described. A 35-year-old white male presented with a painful mass in the perineum without priapism. Diagnostic evaluation with sonography and magnetic resonance imaging revealed a thrombosis in the left posterior corporal body. Treatment consisted of intravenous heparin followed by prophylactic acetylsalicylic acid. The thrombosis resolved spontaneously over several months without sequelae. Conservative management of this rare disease appears to be possible and safe.

Adult↗