Hodgkin's disease and lactic acidosis.
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Acidosis, Lactic↗
Biomedical subjects
G Sander
Publications and source records attributed to G Sander.
[Is autologous chondrocyte implantation a technology suitable for ambulatory health care?].
Statutory ambulatory health care services provided by physicians in Germany are specified by a joint committee of physicians and sickness funds, the Federal Committee of Physicians and Sickness Funds. To ensure that only effective interventions are covered, new medical technologies must demonstrate evidence of clinical effectiveness, cost-effectiveness and medical necessity. Due to increasing demands for reimbursement of autologous chondrocyte implantation, the Committee recently assessed this procedure. Autologous chondrocyte implantation (ACI) is a surgical procedure to reestablish the chondral layer in the knee following trauma. Such injuries may subsequently lead to osteoarthritis, and may eventually require joint replacement. Although the U.S. Food and Drug Administration (FDA) approval of ACI limits its usage to treatment of specific knee defects, other indications, such as for chondromalacia patellae, are promoted by proponents of the technology. The Committee conducted a thorough literature review and examined the status of ACI in other health care systems. Reimbursement of this technology was declined for the following reasons: the effectiveness of ACI has not yet been established in long term, comparative studies, and the procedure involves a type of operation not suitable for the ambulatory health care sector. Other public health insurance systems, such as in Switzerland and Canada, have not yet introduced funding for ACI, and an assessment is currently being conducted by the UK National Institute for Clinical Excellence (NICE). Autologous chondrocyte implantation is a technology that will compete with various other new interventions to correct chondral defects of the knee. It is essential that the treatment effect of ACI be demonstrated in clinically sound, comparative trials before this technology is introduced into the public health care system.
Ambulatory Care↗
[Age-related macular degeneration--a public health problem].
Verteporfin for the treatment of age related macular degeneration was identified as a potential breakthrough technology by the Working Group on Medical Procedures of the German Standing Committee of Physicians and Sickness Funds in spring 2000. Consequently, a formal review was undertaken to assess the benefits and risks of this treatment in order to evaluate its future status in German statutory ambulatory health care. The treatment effect of verteporfin was established in a high quality randomized controlled trial, for the predominantly wet, classic type of choroidal neovascularization secondary to age related macular degeneration. For this patient group, verteporfin is regarded as a reasonable and necessary procedure as there is no effective alternative therapy for this type of macular degeneration. However, the treatment stabilizes the patient's vision rather than improves it and the long term effects must still be evaluated in further clinical trials. After a thorough review of the scientific literature and the statements of various stakeholders the Standing Committee decided to introduce this technology into the statutory healthcare benefits package. For the most effective use of this treatment it must be assured that, prior to treatment, the AMD type (wet vs. dry, classic vs. occult) is correctly diagnosed (using fluorescein angiography) and documented by specially trained physicians. For this reason a stringent quality assurance guideline was developed to prevent the use of this costly technology for non-approved indications. Further indications for this therapy are currently under evaluation in randomized controlled trials. Hence, this decision will need to be updated in future.
Aging↗
[Usefulness and necessity of unsynchronized photosolotherapy and bath-PUVA--two variants of balneophototherapy--in funded ambulatory health care].
The Standing Committee of Statutory Health Insurance Physicians and Sickness Funds is the legal body that makes decisions on reimbursement for health care services in the German ambulatory health care sector. In 1994 the committee declined the reimbursement of balneophototherapy. Balneophototherapy comprises a bath in a saline solution followed by ("non-synchronous") or simultaneous ("synchronous") UVB-irradiation. Photochemotherapy with bath-water delivery of psoralens combined with UVA light is also covered by the term balneophotherapy. The main indication for both procedures is serious psoriasis. Bath PUVA was also recommended for atopic dermatitis, pityriasis lichenoides, lichen ruber and mycosis fungoides. An effectiveness study sponsored by the sickness funds with rather poor methodological design and conduct was not able to show an unbiased effect of balneophototherapy despite inclusion of thousands of patients. On the contrary, a poor adherence of patients and doctors was documented, since 63% of patients suffering from psoriasis and treated with saline bath followed by UVB-irradiation stopped early or used additional therapies like cortisone or vitamin D3 derivatives. Only 43% of patients suffering from psoriasis and treated by bath PUVA did not stop the initial therapy and did not receive additional therapy (UVB, cortisone). In addition, the committee also conducted a thorough review of the literature, guidelines and status in other health care systems. Finally the two modifications of balneophototherapy were again declined from reimbursement in the German ambulatory health care sector. There were no controlled clinical trials showing efficacy of saline bath followed by UVB irradiation. Up to now bath PUVA was only evaluated in small equivalence trials which despite the fact that a drug was tested did not apply basic ICH standards (international conference on harmonisation) for equivalence trials. Additionally, the long-term cancer risk inherent to the application of psoralenes must be considered. Since the definition of "severe psoriasis" is not trivial a wide use of bath PUVA in ambulatory health care has to be based on the results of rigorously conducted clinical trials showing the effectiveness, safety and appropriateness in comparison to other treatment modalities. In reaction to the decision of of the committee two randomised controlled trials for the evaluation of the efficacy of balneophototherapy are planned.
Balneology↗
[Reimbursement and importance of hyperbaric oxygenation for diabetic foot ulcers in German publically funded ambulatory health care].
The Standing Committee of Statutory Health Insurance Physicians and Sickness Funds is the legal body that makes decisions on reimbursement for health care services in the German ambulatory health care sector. In 1994, the Committee declined the reimbursement of hyperbaric oxygen therapy (HBO). In 1999, a new deliberation of the efficacy, appropriateness and cost-effectiveness of HBO was initiated as the proponents of this technology claimed that the efficacy of HBO had since been proven in clinical trials. The deliberation was announced and published in the journal of the German Medical Association (Deutsches Arzteblatt) and the federal register (Bundesanzeiger). All institutions, groups, and interested individuals were given the opportunity to provide a written statement. The statements and, in particular, the scientific literature cited in those statements, were critically appraised by the Committee. In addition, the Committee conducted a thorough review of the literature, guidelines and status of the therapy in other health care systems. More than 40 potential indications for the use of HBO were reviewed by the committee. One indication was for diabetic foot ulcers. Most clinical trials related to this field represented only retrospective case series, which, in view of the established therapies, cannot be used as a sound basis for the acceptance of HBO as a new technology for the therapy of diabetic foot ulcers. Some studies were planned as randomized controlled trials but had serious methodological flaws in conduct and analysis. The main problems were the low numbers of patients included and serious inbalances of important and well known prognostic factors between the treatment groups. Systematic reviews that were published in the international literature after the decision of the Committee drew similar conclusions in view of the methodological flaws in the clinical trial data. In summary, the Committee decided once again to decline coverage of HBO in German ambulatory health care.
Ambulatory Care Facilities↗
Expression of the homeobox gene, Barx2, in wool follicle development.
We have cloned ovine Barx2, a member of the Bar class of homeobox genes, and present the first description of Barx2 expression in wool follicle development. Barx2 is uniformly expressed in the embryonic ectoderm but is transiently downregulated during the initiation of follicle morphogenesis. Subsequently, Barx2 is expressed throughout the epithelial component of the developing follicle except for a small group of cells at the leading edge of the follicle placode. These Barx2-negative cells are destined to form the follicle bulb and are the progenitors of the inner root sheath and hair shaft. In adult follicles, Barx2 is expressed throughout the outer root sheath but not in the inner root sheath or hair shaft, or in dermal cells associated with the follicle. The pattern of Barx2 expression in follicle morphogenesis is similar to that of the cell adhesion molecule E-cadherin, a similarity that echoes Barx2 coexpression with the L1 cell adhesion molecule in other tissues during mouse embryogenesis. Barx2 is also expressed in tongue and esophagus, two other keratinizing tissues, and we speculate that Barx2 may have a general function in controlling adhesive processes in keratinizing epithelia.
Animals↗
Serial echocardiographic and clinical evaluation of valvular regurgitation before, during, and after treatment with fenfluramine or dexfenfluramine and mazindol or phentermine.
OBJECTIVE: The prevalence of cardiac valvular regurgitation demonstrated by echocardiography in patients who took appetite-suppressant medication for weight loss has been assessed at 5%-30%. We studied 86 patients who had echocardiograms before treatment with appetite suppressants to determine the incidence of new cases and to evaluate the clinical implication of the echocardiographic findings. RESEARCH METHODS AND PROCEDURES: We studied 69 men [Mean+/-Standard Deviation (S) age 49+/-8] and 17 women (mean+/-S age 50+/-7) who had 233 echocardiograms before, during, and after a weight-loss program that used predominantly fenfluramine (or dexfenfluramine) with mazindol (or phentermine). Mean drug exposure was 17 months. Blinded echocardiographic readings were performed to identify and grade aortic regurgitation (AR) or mitral regurgitation (MR). RESULTS: Seven of 86 patients (8%) had pre-existing regurgitation with five (6%) meeting our case definition. Thirteen (16.5%) of initially normal patients developed valvular regurgitation and were new cases. Of the new cases, 12 were grade I/IV AR and one was both grade II/III MR and II/IV AR. All 13 patients were asymptomatic, and only two aortic insufficiency murmurs could be auscultated. There was significantly greater risk for developing valvulopathy for those who took medications longer than 6 months (p = 0.03), and no new cases were observed in patients exposed for less than 8 months. No increased risk associated with age, presence of hypertension, or exposure to fenfluramine-phentermine combination was demonstrated. Although there was a higher incidence of new regurgitation in women (31% vs. 13% for men), this was not statistically significant (p = 0.093). DISCUSSION: Some patients who had normal echocardiograms at baseline developed cardiac valvular regurgitation after exposure to fenfluramine or dexfenfluramine with mazindol or phentermine. The development of valvulopathy was significantly correlated with duration of exposure. The clinical implications of echocardiographically demonstrated regurgitation are uncertain, since there were only two audible murmurs and no other clinically relevant signs or symptoms among the patients.
Aortic Valve Insufficiency↗
[New MR contrast media in liver diagnosis. Initial clinical results with hepatobiliary Eovist (gadolinium-EOB-DTPA) and RES-specific Resovist (SH U 555 A)].
The purpose of this work is to describe our initial clinical experience (in 66 patients) with Resovist and Eovist, two new liver-specific MR contrast agents. We focus our report on safety aspects, dose finding, and optimization and technical parameters. Both contrast agents were well tolerated and improved the detectability of focal liver lesions. With Resovist, postcontrast MRI may be started as early as 10 min following injection. The dose of 8 mumol Fe/kg bodyweight was sufficient to achieve diagnostic tumor-liver contrast levels. Since Eovist can also be administered as a bolus, dynamic enhancement patterns may be studied for tumor characterization as well. Breath-hold T1-weighted FLASH images were superior to other T1-weighted techniques with and without fat saturation.
Contrast Media↗
Circadian variation in blood pressure and heart rate in nonhypertensive congestive heart failure.
This study was designed to determine whether decreases in the circadian variability of arterial blood pressure and heart rate measured in ambulatory patients would correlate with neurohumoral indices of the severity of congestive heart failure not the result of systemic arterial hypertension, and whether treatment with angiotensin-converting enzyme (ACE) inhibitors would restore a more normal pattern. The study also examined the ability of ambulatory blood pressure monitoring to discern pharmacodynamic patterns in patients with congestive heart failure, which is associated with decreased variability in circadian variations in blood pressure and heart rate among hospitalized patients. Increased plasma norepinephrine, renin activity, and atrial natriuretic peptide (ANP) have a positive correlation with worsening clinical status. ACE inhibitors have been found to be beneficial in the treatment of congestive heart failure. Ambulatory 24-h blood pressure and neurohumoral measurements were recorded in 30 patients with congestive heart failure (class II-IV, New York Heart Association) before treatment with lisinopril or captopril and repeated after 6 weeks of treatment. Fourier analysis was used as a curve-smoothing technique to compare the pharmacodynamics of the two ACE inhibitors. The absolute amplitude of systolic blood pressure correlated inversely with plasma norepinephrine and ANP (p = 0.004) but not with renin activity. Mean 24-h systemic arterial blood pressure did not decrease significantly after treatment with ACE inhibitors. An increase in absolute amplitude of systolic blood pressure correlated inversely with baseline amplitude (p < 0.00001). Inspection of the Fourier-smoothed curves demonstrated differences in the circadian effect of lisinopril and captopril on systolic blood pressure and rate-pressure product. Ambulatory 24-h blood pressure monitoring may prove useful in the assessment of the severity and treatment of congestive heart failure.
Adult↗
Social stress in tree shrews increases the whole-body RNA degradation rates.
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Animals↗
Interrelation between whole-body turnover rates of RNA and protein.
In our search for new non-invasive methods to determine metabolic and nutritional state, we have identified several specific, modified, urinary one-way catabolites of rRNA, tRNA and mRNA which permit the assessment of the whole-body turnover of these RNA classes. A comparison of the steady-state turnover of RNA and the proteins actin plus myosin (determined using urinary 3-methylhistidine) in preterm infants and adults showed that preterm infants have about 3 times higher average turnover rates per unit body weight than adults of tRNA and rRNA as well as of actin plus myosin, whereas calculated mRNA turnover was 6 times higher in preterm infants than in adults. These as well as our recent observations of RNA turnover in different mammals are compared here with data on whole-body protein turnover and basal metabolic rates (BMR) in different mammalian species including man, for which data are available. The turnover rates of tRNA, rRNA, protein and energy (BMR) can be described by the relation, turnover = const. x body mass (exp.), the extrapolated exponents being 0.69-0.78. This suggests a common underlying principle, possibly energy turnover, as cause for the coordinated whole-body turnover rates of RNA and protein in the steady state.
Adult↗
3-Methylhistidine/creatinine ratio in urine from low-birth-weight infants. Statistical analysis.
3-Methylhistidine and creatinine concentrations were determined in 45 24-hour urine samples collected in 380 single voidings from 23 preterm infants (gestational age: 30-36 weeks, median: 33 weeks; birth weight: 1,613 +/- 219 g; age: 9-83 days postpartum) and from 7 infants small for gestational age (birth weight: 2,061 +/- 203 g; age: 2-30 days postpartum). Statistical analysis shows that diurnal variations of the ratio 3-methylhistidine/creatinine are negligible. The variability of this ratio is chiefly caused by differences in excretion on different collection dates and is probably due to differences in the metabolic state. Hence the determination of 3-methylhistidine/creatinine ratio in single voidings is sufficient even in low-birth-weight infants. In our collective the mean 3-methylhistidine/creatinine ratio for healthy, well-growing low-birth-weight infants (n = 21) was 19.6 +/- 2.3 mumol/mmol. Infants with stagnating or decreasing weight (n = 5) showed 3-methylhistidine/creatinine ratios clearly above that of the normal group.
Body Weight↗
3-Methylhistidine/creatinine ratio in urine from low-birth-weight infants. Clinical approach.
Single urine voidings were collected twice a week in the clinical course of 12 low-birth-weight infants (gestational age: 31.8 +/- 2.8 weeks; birth weight: 1,383 +/- 308 g) and analyzed for 3-methylhistidine and creatinine. The mean 3-methylhistidine/creatinine ratio for 6 healthy, well-fed, growing low-birth-weight infants was 20.2 +/- 1.9 mumol/mmol. In the clinical course of single individuals a rise of urinary 3-methylhistidine/creatinine ratio was observed in cases of acute infection and/or low energy supply (less than 100 kcal/kg/day) frequently coupled with insufficient weight gain. Mean 3-methylhistidine/creatinine ratios in infants with hyaline membrane syndrome under artificial respiration were generally higher than in the controls matched for energy supply.
Body Weight↗
Determination of 7-methylguanine, N2,N2-dimethylguanosine, and pseudouridine in ultrafiltrated serum of healthy adults by high-performance liquid chromatography.
7-Methylguanine (m7Gua), N2,N2-dimethylguanosine (m2(2)Guo), and pseudouridine (psi) are degradation products from RNA turnover and can be used as markers for the whole-body turnover of mRNA-cap, tRNA, and rRNA (in healthy individuals, urinary excretion of these catabolites follows a regular pattern; the relative molar ratio of psi:m7Gua:m2(2)Guo is approximately 100:19:6). HPLC methods were developed to measure serum concentrations of these RNA catabolites after deproteinization of the samples by ultrafiltration through microcollodion bags with a nominal exclusion Mr of 12,400. For healthy adults the following values (mean +/- SD) were found: psi, 2760 +/- 460 nmol/liter (n = 10); m7Gua, 129.7 +/- 24.0 nmol/liter (n = 13); m2(2)Guo, 31.0 +/- 3.7 nmol/liter (n = 9). The relative molar ratio of these substances in serum derived from our data is approximately 100:4.7:1.1. 7-Methylguanosine (m7Guo) added to serum is to a large extent converted to the corresponding free base, m7Gua, the form which is excreted in urine.
Adult↗
[Roentgen stereophotogrammetry in the diagnosis of the maxillofacial area].
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Facial Bones↗
Ribonucleic acid turnover in man:RNA catabolites in urine as measure for the metabolism of each of the three major species of RNA.
Urinary excretion of the non-reusable modified RNA catabolites pseudouridine (psi), 7-methylguanine (m7Gua) and N2,N2-dimethylguanosine (m2(2)Guo) was measured in preterm infants and in adults. The values (in mumol/mmol of creatinine) were: for preterm and 'small for gestational age' infants (n = 26; number of samples = 38) psi = 164 (SD 32), m7Gua = 39.1 (SD 9.0), m2(2)Guo = 10.6 (SD 2.1); for adults (n = 32) psi = 25.3 (SD 3.1), m7Gua = 4.8 (SD 0.89), m2(2)Guo = 1.53 (SD 0.42). Our measurements were compared with an expectation derived from the average cellular distribution of psi, m7Gua and m2(2)Guo between rRNA, tRNA and mRNA. m2(2)Guo occurs exclusively in tRNA, psi in both rRNA and tRNA, and m7Gua in all three RNA classes, in proportions which can be estimated for the steady state. Urinary excretion of psi and m2(2)Guo should reflect their steady-state distribution, since rRNA and tRNA have been shown to have similar turnover rates in mammalian tissues. We conclude that we can use the excretion of m2(2)Guo to assess whole-body tRNA turnover. Since tRNA contains psi in a constant proportion to m2(2)Guo, the proportion of urinary psi stemming from tRNA can be estimated, and the remainder (approximately 60-65%) is an indicator of rRNA turnover. Finally, the excretion of m7Gua far exceeds the proportion predicted to come from rRNA and tRNA. We ascribe this excess (approximately 60-70% of the total) to the turnover of the mRNA 'cap'-structure, which is typical for all higher organisms. mRNA turnover is known to be much higher than that or rRNA or tRNA.(ABSTRACT TRUNCATED AT 250 WORDS)
Adolescent↗
Protein and RNA turnover in preterm infants and adults: a comparison based on urinary excretion of 3-methylhistidine and of modified one-way RNA catabolites.
Urinary excretion of 3-methylhistidine in preterm infants (n = 42; 1,712 +/- 408 g, 4-91 days old) was 24.2 +/- 6 mumol/mmol creatinine or 2.26 +/- 0.56 mumol/kg body weight X day. In adults (n = 6; 66 +/- 10 kg, 17-50 years), the corresponding values were 10.5 +/- 1.1 mumol/mmol creatinine and 2.21 +/- 0.23 mumol/kg body weight X day. For both collectives, the breakdown per kg body weight of 3-methylhistidine-containing protein (i.e. actin and myosin) was similar, at approximately 0.7 g/kg X day (preterm infants 0.84, adults 0.60). Since the preterm infants studied contain approximately 21% muscle instead of the 43% found in adults, the 3-methylhistidine excretion in preterm infants probably indicates muscle (and intestinal) protein turnover to be about 3 times higher than in adults, a figure in accord with data on whole-body protein turnover in preterm infants and adults (approximately 15 g/kg X day and approximately 4 g/kg X day, respectively). Urinary excretion of pseudouridine (psi), 7-methylguanine (m7Gua) and N2, N2-dimethylguanosine (m2(2)G) can be used to estimate the turnover of rRNA, mRNA and tRNA, respectively. The values obtained (in mumol/mmol creatinine) in preterm infants are for psi: 164 +/- 32; for m7Gua: 39.1 +/- 9; and for m2(2)G: 10.6 +/- 2.1. In adults, the values are for psi: 25.3 +/- 3.1; for m7Gua: 4.8 +/- 0.89; and for m2(2)G: 1.53 +/- 0.38. This yields 3-4 times higher turnover rates in preterm infants than in adults for all 3 RNA classes: rRNA, 0.1 versus 0.038; tRNA, 1.87 versus 0.66; mRNA 2.35 versus 0.64 mumol/kg X day.
Guanine↗
Possible use of urinary modified RNA metabolites in the measurement of RNA turnover in the human body.
Modified building blocks are found in rRNA, tRNA and mRNA. Apart from pseudouridine these are mostly base- or ribose-methylated nucleosides. If these compounds are neither recycled nor degraded, they should be quantitatively excreted. For pseudouridine (Weissman et al., 1962; Dugaiczyk & Eiler, 1966) and 7-methylguanine (Craddock, Mattocks & Magee, 1968), urinary excretion has been shown to be quantitative. Since the turnover rates of rRNA and tRNA, which contain most of the modified nucleosides, are similar within a given tissue, compounds found only in these two classes of RNA should appear in urine in approximately the proportions in which they are present in the body. Using pseudouridine as internal standard, we show this indeed to be likely for one of the major RNA catabolites in human urine, N2,N2-dimethylguanosine, a compound present only in tRNA. By contrast, 7-methylguanine is excreted in threefold larger amounts than can be explained by joint provenance from tRNA and rRNA only; the remainder we assume to come from the 'cap' structure of mRNA, known for its high turnover. We suggest that one can use the urinary excretion of pseudouridine, N2,N2-dimethylguan(os)ine and 7-methylguanine to assess the whole-body turnover rates in man of rRNA, tRNA and mRNA, respectively. Such data may be useful to define whole-body metabolic activity.
Animals↗