Biomedical subjects

R Dietrich

Publications and source records attributed to R Dietrich.

At least 37 records · Page 2Linked to original sources

PubMed1992

Congenital disorders of sexual differentiation: MR findings.

A broad spectrum of anomalies of sexual differentiation may exist at birth. These include male and female pseudohermaphroditism, gonadal dysgenesis, and true hermaphroditism. When ambiguous genitalia are present, expedient identification of the anomaly is required for proper gender assignment and appropriate surgical or hormonal correction. As the appearance of the external genitalia often is not distinctive enough to make a specific diagnosis, this must be accomplished by clinical findings along with a combination of cytogenetic, biochemical, and radiologic studies. Because the causes of abnormal sexual differentiation are diverse and often exhibit incomplete expression, they produce much anatomic variability. Sonographic and radiographic studies are often used initially to evaluate such conditions. The noninvasive multiplanar nature of MR imaging makes it a useful alternative method with which to characterize the abnormal anatomy in this group of disorders, as we illustrate in this pictorial essay.

Disorders of Sex Development↗

PubMed1991

Changes of dipeptidylpeptidase IV as a membrane marker of lymphocytes in acute and chronic liver diseases--biochemical and cytochemical investigations.

Lymphocytic dipeptidylpeptidase IV (DPP-IV, E.C. 3.4.14.5) is described as a marker enzyme of immunostimulant T-lymphocytes as well as functional characteristic of interleukin-2-producing cells. Cytochemical staining of DPP-IV positive lymphocytes and measurements of DPP-IV activity in mononuclear cells and in sera of patients suffering from different kinds of liver diseases were performed to evaluate the average activities in positive cells. The results demonstrated that this serine exopeptidase exhibits extremely low activity in autoimmune chronic hepatopathies. On the contrary, hepatitis-B-associated liver diseases were connected with markedly increased values. Furthermore, significant differences of DPP-IV activity were found in different kinds of acute and chronic liver diseases. These findings are discussed in connection with the participation of dipeptidylpeptidase IV in impaired immunoregulation of the altered liver.

Acute Disease↗

PubMed1991

[Chronotherapy concept and the pharmacokinetic validation of a theophylline retard preparation for once-nightly administration (Euphylong)].

Many patients with asthma often experience a deterioration of symptoms at night and in the early morning resulting in sleep disruption and possibly impaired daily performance. A bronchodilator agent which exerts its maximal effect overnight to control nocturnal symptoms, without a worsening of the disease during the daytime, should improve the treatment of asthma. In the case of theophylline, it has been shown in asthmatic patients that a chronotherapeutically optimized formulation which provides the highest serum theophylline concentrations during the critical early morning hours resulted in better airflow levels overnight than the conventional twice daily regimen without loss of airflow in the afternoon. During clinical routine, this chronotherapeutically optimized drug delivery can only be ensured if there is no food interaction. In particular, dose dumping must be excluded. One absolute prerequisite for this is the pH-independent drug release in vitro. In addition to a "state-of-the-art" biopharmaceutic formulation, an easy-to-use guidance for individualizing the theophylline dose should be provided. This in turn is only possible if the concentration/time profiles show good reproducibility between subjects, from day to day, and for different dose levels. Finally, batch-to-batch bioequivalence has to be ensured. It is shown that Euphylong satisfies all of the above requirements.

Asthma↗

PubMed1990

A simulation model for evaluating a set of emergency vehicle base locations: development, validation, and usage.

This paper describes our experiences in developing a simulation model for evaluating a set of emergency response vehicle base locations. The project was undertaken jointly by the University of Arizona and the Tucson Fire Department. The issues of model development, data collection, model validation, and experimentation are discussed. The critical nature of the problem and the clients' lack of experience with mathematical models, made model validation the major step in gaining user acceptance. We show that looking solely at standard performance statistics such as the calls successfully serviced, may lead to the acceptance of an invalid model. We also show that the high level of detail used in many simulation models for evaluating base locations is unnecessary in the current case. An analysis evaluating two alternative sets of locations for the Tucson system is discussed.

Ambulances↗

PubMed1990

Formation of gluconeogenic precursors in rat skeletal muscle during fasted-refed transition.

During the fasted-refed transition, hepatic glycogen repletion from glucose can occur by the direct and indirect pathway. In the indirect pathway, glucose is first metabolized to 3-carbon intermediates that then are converted in the liver to glucose 6-phosphate via the gluconeogenic pathway before conversion to glycogen. The present study evaluated whether skeletal muscle is a major source of 3-carbon intermediates (i.e., lactate, pyruvate, and alanine) during refeeding of 1-day fasted rats. Arteriovenous differences for lactate, pyruvate, and alanine across the anesthetized rat hindlimbs were used to evaluate muscle metabolism in the fed, fasted, and refed state. In the fasted state, liver glycogen was depleted, and muscle released 3-carbon intermediates. One hour after refeeding, hepatic glycogen was 30% repleted, and blood lactate, pyruvate, and alanine increased. Despite this, the release of alanine by muscle diminished at this time and lactate was removed. At 4 h after refeeding, 3-carbon intermediates were all released by hindlimb tissue but in an amount not greater than in the fasted state. Overall, these results suggest that skeletal muscle in the rat is not a major source of 3-carbon precursors for early postprandial hepatic glycogen repletion via the indirect pathway, nor is the rise in 3-carbon intermediates in blood during refeeding caused by their increased output by muscle.

Alanine↗

PubMed1990

Exercise-induced hyperammonemia in patients with compensated chronic liver disease.

Plasma levels of ammonia and amino acids were measured during and after graded physical exercise in seven ambulatory patients with well-compensated chronic liver disease and in seven healthy controls. Plasma ammonia was similar in both groups at rest but reached significantly higher peak values (124.0 +/- 29.3 (SD) versus 74.7 +/- 17.7 mumol/l) in the patients with liver disease during exercise. The return to base line during the recovery period was delayed in the patients (T1/2 9.9 +/- 5.5 versus 2.3 +/- 1.0 min). Except for plasma taurine, which was significantly lower in the patients at rest and which showed a significant decrease in the controls but not in the patients during exercise, changes in the plasma concentration of amino acids were similar in the two groups. The increased exposure of patients with chronic liver disease to ammonia while performing an identical workload results from an impaired clearance of ammonia plus, possibly, an increased generation of ammonia in muscle working at a higher intensity. Since hyperammonemia may be associated with the sensation of fatigue, increases in plasma ammonia during daily physical activities might in part explain the easy fatigability often reported by patients with chronic liver disease.

Adult↗

PubMed1990

[Dipeptidylpeptidase IV activity in human lymphocytes in hepatobiliary diseases].

Lymphocytic dipeptidylaminopeptidase IV (DP-IV; E.C.3.4.14.5.) is described as a marker enzyme of immunostimulant T-lymphocytes as well as functional characteristic of IL-2-producing cells. Mononuclear cells of periphere blood (MNC) were isolated by density gradient centrifugation followed by enzymcytochemical staining of DP-IV positive cells and measuring of DP-IV enzyme activity using chromogenic substrates. As relative sign of single cell DP-IV activity we calculated average DP-IV activities of DP-IV positive cells. Blood samples from 14 patients with acute virus hepatitis, 30 cases of chronic active liver disease, 61 cases with liver cirrhosis of various kind and 19 patients with fatty liver and toxic hepatitis were investigated. As standard of comparison we used a group of healthy blood donors. By this way significant differences of described DP-IV parameters between some groups of liver disease were evident. Using an aetiologic classification of investigated liver diseases we found highly significant increased single cell activities in hepatitis-B associated cases in comparison to remarkable lower lower values in autoimmune cases. Different hypothesis about changes of lymphocytic dipeptidylaminopeptidase IV as a part of disturbed immunoregulation in chronic liver diseases were discussed.

Chemical and Drug Induced Liver Injury↗

PubMed1989

A survey on the occurrence of Fusarium mycotoxins in Bavarian cereals from the 1987 harvest.

Bavarian cereals and wheat flour from the 1987 harvest were analysed for nivalenol (NIV) and deoxynivalenol (DON) using high performance liquid chromatography (HPLC) and for T-2 toxin and zearalenone (ZEA) by enzyme-linked-immunosorbent assay (ELISA). The study included 190 field samples of wheat, barley, rye and oat with visibly damaged ears, 45 samples of wheat intended for feed production and two series of wheat flour (type 550) and whole wheat flour collected in October 1987 and June 1988. The field samples examined showed a high DON contamination of wheat (87%) with an average of 3.96 mg/kg and a maximum of 43.8 mg/kg. Mean levels between 0.33 mg/kg and 0.27 mg/kg DON could be detected in barley, rye and oat. Of the wheat samples, 58% contained ZEA with a maximum of 1.560 mg/kg. The highest levels of ZEA were detected in samples which also showed high concentrations of DON. The NIV and T-2 toxin levels were comparatively low. Thirty percent of the samples showed NIV concentrations between 0.04 mg/kg and 0.29 mg/kg and 38% contained between 0.005 and 0.60 mg/kg of T-2. In the wheat samples for feed production, only DON was detected with an average of 0.190 mg/kg and a maximum of 0.75 mg/kg. The highest DON levels (0.58 mg/kg) from October 1987 were found in the wheat flour samples which were lower than the highest DON concentration (3.24 mg/kg) detected in the samples collected during June 1988. This fact was probably due to a substantial amount of non-contaminated wheat from 1986. The toxin concentrations in the whole wheat flour were not higher than in the type 550 flour.(ABSTRACT TRUNCATED AT 250 WORDS)

Animal Feed↗

PubMed1989

Use of magnetic resonance imaging in planning the separation of omphalopagus conjoined twins.

Magnetic resonance imaging (MRI) was used for the first time in the preoperative planning for separation of conjoined twins. In these omphalopagus infants, MRI showed normal biliary and cardiovascular structures and demonstrated, in detail, a relatively avascular plane through the liver bridge, which enabled safe separation with minimal blood loss at 3 1/2 months of age. A single MRI study supplied information superior to that obtained with multiple previously available imaging studies. MRI should be an essential part of the preoperative workup of all types of conjoined twins.

Abdomen↗

PubMed1989

[A report on the status of the compilation of the registry paper: "cardiac pacemaker patients"].

On the basis of valid legal arrangement in the GDR to take radiomedical measures in heart pace-maker patients a standardized practice in irradiation planning and a standardized documentation are represented. With this a central registration and analysis of pace-maker patients in radiotherapy can be done to same aspects. The documentation comprehends measures of carrying out radiotherapy, which have been fixed within irradiation planning and risk estimation, and during therapy ascertained measuring values and observations for estimate of heart-circulation-situation of the patient and of the technical state of the pace-maker. The documentation is recommended for application in agreement with the Society for Radiology of the GDR. The Clinic and Policlinic for Radiology of the Martion Luther University Halle-Wittenberg is proposed for central registration and analysis.

Germany, East↗

PubMed1988

Acquired cystic kidney disease in children undergoing long-term dialysis.

Acquired cystic kidney disease (ACKD) occurs in adult patients undergoing long-term dialysis. Early detection is important because clinically significant hematuria and malignancies are associated with ACKD. We evaluated by magnetic resonance imaging (MRI) and ultrasonography (US) the incidence of ACKD in 15 patients aged 7.3-21.6 years (mean 15.9 years) with non-cystic primary renal disease. Nine patients had been treated with peritoneal dialysis only, and 6 with both hemodialysis and peritoneal dialysis for 24-73 months (mean 37 months). Three patients (20%) had no cysts. In 5 patients (33%) with bilateral multiple cysts, the diagnosis of ACKD was made by MRI and US. In another 5 patients, solitary cysts were localized to one kidney by MRI, and in 2 patients solitary cysts were seen in both kidneys. This study documents that ACKD is not limited to older patients with end-stage renal disease. Early detection of these cysts can be accomplished by MRI and is warranted since 1 patient developed neoplastic tubular changes which can precede tumor formation.

Adolescent↗

PubMed1988

Magnetic resonance imaging of iron overload in children treated with peritoneal dialysis.

The ability of magnetic resonance imaging (MRI) to detect iron overload in children with end-stage renal disease (ESRD) was studied in 18 multiply transfused patients, aged 15.5 +/- 4.8 years, and 5 nontransfused children without evidence of renal disease. In the transfused patients, the serum ferritin (SF) level was compared to (a) a subjective rating of signal intensity of MRI images (scale of 0-10), (b) mean T1 values of liver and spleen, and (c) computer-assisted measurements of spin echo intensity (SEI) of liver, spleen, muscle and fat tissue. On subjective evaluation, the mean signal intensity was significantly lower in transfused patients than in controls and a significant correlation with the SF levels was observed for ratings of both liver and spleen. Mean T1 values of liver and spleen did not correlate with the SF levels. On computer analysis, the ratios of SEI of fat/liver, fat/spleen, muscle/liver and muscle/spleen were significantly correlated with the SF levels as well as the subjective evaluation sources. These data indicate that MRI is a suitable technique of documenting the presence and degree of iron overload in multiply transfused children with ESRD.

Adolescent↗

PubMed1988

Encephalitis lethargica-like illness in a girl with mycoplasma infection.

We describe a patient with mycoplasma infection and clinical manifestations of encephalitis lethargica. The patient was brought to our attention after acute neurologic deterioration followed by a prolonged sleep-like state and the emergence of extrapyramidal features. MRI of the brain disclosed a striking pattern of subcortical involvement by the inflammatory process, corroborating the clinical picture.

Brain↗

PubMed1988

Galenical development of a new sustained-release theophylline pellet formulation for once-daily administration.

Euphylong is a sustained-release product consisting of encapsulated pellets covered with a porous membrane. Since the mechanism of release is osmotic, this new formulation has been termed a "micro-osmotic system". The course of theophylline release is linear over a wide range and is independent of pH value, surface tension and buffer concentration of the dissolution medium. Furthermore, the in-vitro release remains largely uninfluenced by the dissolution model used and by agitation of the dissolution medium. Variations in the in-vitro release profiles produce variations in the in-vivo absorption profiles determined by deconvolution. It is therefore possible, irrespective of the dissolution model and medium used, to produce in-vitro release profiles that enable in-vivo absorption to be predicted by varying the thickness or porosity of the membrane.

Adult↗

PubMed1988

Validation of the pellet coating process used for a new sustained-release theophylline formulation.

Within the scope of the validation process described in this report, the influence of the process parameters on the factors determining the quality of Euphylong pellets during the spraying process is examined. The process is challenged within the meaning of the validation guidelines. Investigations within the scope of product-independent validation of the automated fluid bed coating apparatus (Wurster setup) used here provide the basis for installation qualification and operational qualification as defined by the PIC convention and the GMP guidelines. Within the scope of a classification of risks, potential operating and system errors are examined, giving consideration to the worst case conditions, and the relevance of the "blue book" to the process is discussed. Three critical process parameters (spraying temperature, air velocity and relative humidity) are investigated with respect to their influence on the goal parameter "in-vitro release of the active ingredient after 1 h". Product-related validation of the process is accomplished by means of statistical experimental design (factorial design). Statistical analysis is done using the methods described by Box-Wilson and Yates and by response surface research and grid-search methods via contour plots and isometric graphs. This yields the acceptable range of process parameters with respect to product quality. Finally the differences between validation and optimization are discussed.

Analysis of Variance↗

PubMed1988

Validation of the in-vitro dissolution method used for a new sustained-release theophylline pellet formulation.

The in-vitro release method used within the scope of the galenical development of Euphylong pellets and subsequently employed on a routine basis is described. The suitability of the method is demonstrated by means of the validation procedure. The release system used is based on the standard USP XXI apparatus (paddle method) and consists of three essential components: a) dissolution apparatus (paddle model). b) measuring unit (spectrophotometer), c) data acquisition and analysis system. It is demonstrated that in-vitro release rates of theophylline from Euphylong pellets can be accurately investigated with other models as well, since the course of release is not affected by pH value, buffer capacity, surface tension, turbulence of the dissolution medium or agitation by the apparatus. The accuracy of the method as well as its precision and ruggedness are investigated and described. The influences arising from the withdrawal of specimens from the bulk product and of sampling from the release vessel are discussed. The accuracy of the analytical records generated by the computer system is shown and the ruggedness of the analytical program investigated under "worst case conditions". The documentation of the results obtained is described and examined with respect to reliability in the face of system and operating errors. All pertinent guidelines (GAP, FIP guidelines for dissolution testing, etc.) are taken into consideration and their relevance to the above investigation assessed.

Chemistry, Pharmaceutical↗

PubMed1988

Feasibility of in-vitro/in-vivo correlation in the case of a new sustained-release theophylline pellet formulation.

This contribution attempts to relate the in-vitro drug release properties of theophylline from Euphylong pellets to serum theophylline concentration/time curves. Comparisons are made according to methods presented in recent publications (e.g. using mean residence time) and by juxtaposition of analogous values. For this, the mutual relationship of equal release times (absorption) and % amounts released or absorbed at fixed times are evaluated. The in-vitro data required for the computational evaluations were obtained using a paddle apparatus (according to USP XXI) at 100 rpm, buffer pH 7.4. The feasibility of converting the in-vitro to the in-vivo curve by means of a chronological transformation is examined, as well as in-vitro/in-vivo dependence on numerically fitted model parameters. Finally, in an attempt to imitate the in-vivo curve profile, the apparatus parameters for the in-vitro tests were subjected to extreme variation. The effect of the presence or absence of sink conditions is discussed and evaluated. In the concluding overview, the feasibility of predicting the in vivo behaviour of Euphylong pellets on the basis of current so-called "in-vitro/in-vivo correlation" procedures is assessed.

Absorption↗

PubMed1988

A novel approach to the specification of in-vitro dissolution boundaries based on regulatory requirements for bioequivalence.

Although bioequivalence between products has gained considerable importance over the last few years, the concept has not yet been transferred to "within product bioequivalence", i.e. "batch-to-batch bioequivalence". Two different formulations of an active substance are considered bioequivalent if they differ by not more than 20% in rate and extent of absorption. This regulatory requirement should also be satisfied for two different batches of the same formulation ("within product bioequivalence"). Euphylong pellets appear to be the first sustained-release theophylline formulation for which data on the "within product bioequivalence" can be presented. The upper and lower limits of the in-vitro dissolution were specified so that even the most extreme batches within these specifications, which normally do not occur among production batches, are bioequivalent. This novel procedure requires that the in-vitro method used is suitable to detect in-vivo differences. Furthermore, it should be able to predict the in-vivo absorption kinetics on the basis of in-vitro data, at least insofar as a discriminatory ranking is concerned. It has been shown how this approach has lead to the in-vitro specifications of Euphylong pellets and how specially manufactured experimental batches representing the upper and lower specification limits were tested for bioequivalence. Finally, it is shown that a typical production batch conforms well with the specification limits and does not reach the extremes of the experimental batches which were specially manufactured for the purpose of this study.

Absorption↗