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Biomedical subjects

M Reinhardt

Publications and source records attributed to M Reinhardt.

At least 55 records · Page 3Linked to original sources

Different protective effects of tauroursodeoxycholate, ursodeoxycholate, and 23-methyl-ursodeoxycholate against taurolithocholate-induced cholestasis.

The coinfusion of tauroursodeoxycholate (TUDC) prevents taurolithocholate (TLC) -induced cholestasis. 23-Methyl-ursodeoxycholate (MUDC) is a side-chain derivative of ursodeoxycholate (UDC). If conjugation with taurine is important for the protective effect of UDC, the MUDC may not be as able as TUDC to prevent TLC-induced cholestasis since it is poorly amidated by the liver. To answer this question, isolated livers of adult Sprague-Dawley rats were coinfused with MUDC (UDC, TUDC) and TLC. After 15 min, inflow rates of the bile acids were doubled. In further experiments taurine in excess was added to the coinfused bile acids. The uptake of bile acids was >90% in all groups, irrespective of whether they were perfused alone or in combination. Single perfusion of TLC caused a rapid decrease in bile flow. UDC and MUDC were hypercholeretic; TUDC moderately choleretic. During coinfusion experiments, TUDC not only completely abolished cholestasis but in addition increased bile flow and biliary bile acid secretion. UDC did prevent TLC cholestasis at the lower inflow rates. At high inflow rates, bile flow decreased significantly. Addition of taurine to this bile acid combination did not significantly improve the anticholestatic effect of UDC. At low and high infusion rates of MUDC, cholestasis induced by TLC was reduced very little. Cumulative bile flow over 30 min fell by approximately 70% as compared to that of singly perfused MUDC. Addition of taurine to the coinfused MUDC/TLC slightly, but less significantly, improved the anticholestatic effect of MUDC. Since MUDC is by far less protective than UDC (and TUDC) despite similar physiochemical properties, it is concluded that taurine conjugation of UDC seems to be a prerequisite to prevent TLC-induced cholestasis. The results imply that treatment of cholestatic liver diseases with taurine-conjugated UDC might be more appropriate than with unconjugated UDC in cases where taurine conjugation is defective or where taurine depletion has occurred.

Animals↗

[13C]octanoic acid breath test for non-invasive assessment of gastric emptying in diabetic patients: validation and relationship to gastric symptoms and cardiovascular autonomic function.

Since there is a need for a widely applicable non-invasive test to assess gastric emptying in diabetic patients, we evaluated the sensitivity, specificity, and reproducibility of the [13C]octanoic acid breath test as compared with scintigraphy. Moreover, we examined the relationship between the breath test indices and gastric symptoms, cardiovascular autonomic function, and metabolic parameters. Forty healthy control subjects and 34 diabetic patients were studied. Three indices of gastric emptying, assessed by the breath test, were computed: half-emptying time (t1/2breath), gastric emptying coefficient (GEC), and lag phase. Furthermore, the half-emptying time, measured by scintigraphy (t1/2scint), was calculated and gastric symptoms and cardiovascular autonomic neuropathy (CAN) were scored. The coefficients of variation of day-to-day reproducibility in 10 healthy subjects were 29.6% for t1/2breath, 7.4% for GEC, and 46.5% for lag phase. An abnormal delay for t1/2scint (> 100 min) or t1/2breath (> 200 min) was noted in 12 patients. Based on the results for t1/2scint, the sensitivity of t1/2breath and GEC was 75% and the specificity was 86%. Both t1/2breath (rs = 0.523; p < 0.05) and GEC (r2 = -0.594; p < 0.05) were significantly associated with the gastric symptom score. A significant relationship to the CAN score was demonstrated for t1/2breath (rs = 0.448; p < 0.05), GEC (rs = -0.467; p < 0.05), and t1/2scint (rs = 0.602; p < 0.05). There were no significant associations of the breath test indices with the blood glucose levels during the test, HbA1c, age, and duration of diabetes. In patients with abnormal t1/2scint (n = 12) not only was t1/2breath significantly prolonged and GEC reduced, but also the scores of CAN and gastric symptoms were significantly increased as compared with those who had a normal t1/2scint (n = 22). We conclude that the [13C]octanoic acid breath test represents a suitable measure of delayed gastric emptying in diabetic patients which is associated with the severity of gastric symptoms and CAN but not affected by the blood glucose level.

Adult↗

Assessment of acute myocardial necrosis after cardiopulmonary resuscitation and cardioversion by means of combined thallium-201/technetium-99m pyrophosphate tomography.

Diagnosis of acute myocardial necrosis by means of conventional electrocardiographic criteria or the release of cardiac enzymes is often difficult or even impossible in patients with out-of-hospital cardiac arrest due to ventricular fibrillation with subsequent cardiopulmonary resuscitation including several DC countershocks. Simultaneous thallium-201/technetium-99m pyrophosphate (PYP) tomography was prospectively applied to 57 patients without typical clinical or electrocardiographic signs of acute myocardial infarction within 48 h after successful resuscitation from out-of-hospital cardiac arrest. Scintigraphic evidence of acute necrosis was present in 23/57 patients (40%). Increased 99mTc-PYP uptake in the pericardial tissue was found in 24 patients (42%). Maximal creatine kinase (CK) concentration was increased in 50/57 patients (88%). CK-MB activity averaged 68+/-52 U/l in patients with positive and 17+/-13 U/l in patients with negative tomograms (P<0.0005), demonstrating the validity of 201Tl/99mTc-PYP tomography. It may be concluded that simultaneous 201Tl/99mTc-PYP tomography is a valuable tool for evaluation of myocardial necrosis after cardiopulmonary resuscitation including DC countershock. Acute myocardial necrosis, as indicated by scintigraphy, represents a potential trigger for the occurrence of ventricular fibrillation. Therefore, 201Tl/99mTc-PYP tomography can be recommended in order to guide further diagnostic and therapeutic interventions in patients after cardiopulmonary resuscitation in whom the underlying cause of the occurrence of ventricular fibrillation is obscure.

Acute Disease↗

Markers of foamy virus infections in monkeys, apes, and accidentally infected humans: appropriate testing fails to confirm suspected foamy virus prevalence in humans.

Foamy viruses (FVs) persist in healthy individuals of various mammalian species, including nonhuman primates. Laboratory markers of FV infection are (1) virus in throat epithelium or peripheral blood lymphocytes (PBLs), (2) proviral DNA sequences in PBLs and various solid organs, and (3) antibodies reactive to viral antigens on Western blots, in radioimmunoprecipitation tests, and in immunofluorescence assays. Using PCR and serological tests, we readily detected FV markers in naturally infected African green monkeys, rhesus monkeys, and chimpanzees, as well as in accidentally infected humans. Transmission of simian foamy viruses to humans (by bite or inadvertent laboratory infection) leads to viral markers, without affecting the recipient. Reports on FV-associated clinical disorders (e.g., thyroid or neurological) have remained controversial. In this study we failed to detect, by PCR, viral sequences in the samples from 223 patients, including 16 HIV-infected Africans, 46 Graves' disease patients, and 28 patients with the de Quervain's thyroiditis. Evaluation of 2688 sera from suspected high-risk areas (e.g., Central and East Africa, or high-risk groups such as HIV-infected individuals and patients with AIDS, thyroid, and neurological disorders) did not reveal FV-specific antibodies in a single case. Previously reported FV seroprevalence in various populations has never been verified by appropriate confirmatory tests. The strain of "human foamy virus" has remained a unique isolate. In conclusion, FVs are unlikely--at present--to circulate in human populations.

Africa↗

Improved automated leucocyte counting and differential in newborns achieved by the haematology analyser CELL-DYN 3500.

Automated leucocyte counts in newborns generated by the impedance principle are artificially affected by the high osmotic resistance of some newborn RBC and possibly by the high normoblast numbers present during the neonatal period. Erroneously high WBC counts may result. The haematology analyser CELL-DYN 3500 (Abbott Diagnostika GmbH, Wiesbaden-Delkenheim, Germany) has two different channels for the WBC count, an electrical resistivity (impedance) channel and a laseroptical channel. In combination with facultative extended lysis of resistant RBC before WBC count, this instrument is claimed to be very suitable for newborn blood analysis. We measured the WBC count and differential of 165 blood samples from newborns and cord blood on the CELL-DYN 3500. Reticulocyte count and manual differential including normoblasts were determined. Furthermore, some technical aspects of neonatal blood analysis were evaluated: precision, cell stability, effect of incorrect blood-anticoagulant ratio of small blood collecting tubes. The internal decision making process of the CELL-DYN 3500 selects the result either from the optical channel (identifies and excludes normoblasts) or from the resistivity channel (eliminates resistant RBC). This instrument gives a reliable and accurate WBC count and differential of neonatal samples even in blood samples with normoblasts and lytic resistant RBC. The result given by the CELL-DYN 3500 can be confirmed by a subsequent run in extended lyse mode.

Artifacts↗

Improved dose concept for radioiodine therapy of multifocal and disseminated functional thyroid autonomy.

The present study analyzes the improvement of the outcome of radioidine therapy in non-immunogenic hyperthyroidism by adapting the target dose to the 99mTc-pertechnetate thyroid uptake under suppression (TcTUs) prior to radioiodine therapy. The TcTUs is a substitute for the non-suppressible iodine turnover. The 89 patients presented with a basal thyrotropin level of < 0.1 mU/l, normal values for free triiodothyronine and thyroxine and with multifocal or disseminated thyroid autonomy. These terms describe the scintigraphic distribution pattern of autonomous iodine turnover. Thirty-two patients had a TcTUs between 1.6 and 3.2% (group A) and 57 had a TcTUs > 3.2% (group B). Fifty-five patients (three of group A and 52 of group B) were treated previously for overt hyperthyroidism with antithyroid drugs. Target doses of 150 and 200 Gy were used in both groups and 300 Gy in group B only. Six months after radioiodine therapy, a basal TSH level of > or = 0.5 mU/l as criterion of therapy success was observed in 94% of group A and in 54% of group B. Further differentiation of group B shows an increasing success rate with the target dose used: 45% after 150 Gy, 50% after 200 Gy and 90% after 300 Gy. In patients with a basal TSH level of < 0.5 mU/l after radioiodine therapy, the TcTUs was evaluated again.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

[Coincidence of unifocal thyroid autonomy and follicular carcinoma. Case report].

The case is reported of a 53-year-old man with differentiated thyroid carcinoma within a hot nodule and typical scintigraphic findings of a unifocal adenoma. Preoperative cytology revealed no malignancy. The preliminary histological diagnosis after hemithyroidectomy on the right side was follicular adenoma. The final histological evaluation, however, revealed follicular carcinoma of the thyroid gland. As a result, a thyroidectomy was performed with postoperative radioiodine treatment. The combination of thyroid carcinoma and hot nodules is extremely rare. In all cases of rapid growing nodules or other abnormalities of the thyroid cytological and/or histological verification is mandatory.

Adenocarcinoma, Follicular↗

[Indications for percutaneous radiotherapy in carcinoma of the thyroid gland. Freiburg consensus].

At the University of Freiburg, a consensus was arrived at concerning the place of external radiotherapy in the management of thyroid cancer. External irradiation is always indicated in papillary and folliculary carcinoma in the pT4 stage of pTNM classification but not in those in pT1-3 pN0 stage. In the presence of lymph-node metastases and distant metastases, an individual treatment concept is recommended, which should be set up in an interdisciplinary conference regarding all risk factors, especially the age and sex of the patient, the histology and grading of the tumor and the completeness of tumor resection. Finally, radiotherapy is usually not indicated in medullary thyroid carcinoma, whereas it is always indicated in anaplastic carcinoma.

Adenocarcinoma, Follicular↗

[Iodine deficiency in Southern Badenia--changes during the last 55 years].

Despite the voluntary iodine prophylaxis in Germany no significant change in the iodine supplementation was observed in the last two decades in Southern Badenia. This finding relates to urinary iodine excretion as well as to goiter prevalence and thyroid volume. The comparison with studies from the 30es and 50es shows significant changes, however. There were relevant regional differences in goiter prevalence and iodine supply in Southern Badenia at that time. The supply of more iodine-containing food could be improved for all walks of life by raising the general standard of life. Actually, there are no longer regional differences in iodine supply and goiter volume in Southern Badenia. However, in 95% of patients investigated the urinary iodine excretion is still below the minimum of 150 micrograms iodine/g creatinine recommended by WHO.

Adolescent↗

[Assessment of basal and stimulated TSH in overt and subclinical hyperthyroidism].

A TRH test was performed in 171 consecutive patients with a TSHbasal below the reference range. TSHbasal, TSHstimulated and delta TSH were determined and compared, using assays of the second and third generation. Free thyroid hormones were elevated in 48 and normal in 123 patients. The sensitivity of all evaluated parameters to assess overt hyperthyroidism was between 94 and 98% with both assays, using a defined TSH threshold (mean of patients with overt hyperthyroidism +2 standard deviations). However, specificity was much lower, only 34 and 23%, respectively, for the TSHbasal. Significant improvement followed TRH-testing: specificity rose to 63 and 57%. The superior reproducibility of TSH values in the lower range, using the third generation assays, was of little value in the differentiation between subclinical and overt hyperthyroidism.

Adolescent↗

Absence of foamy virus DNA in Graves' disease.

A report on the high prevalence of foamy virus DNA in lymphocytes from French patients with Graves' disease prompted us to investigate a similar cohort of 41 German patients. Using PCR amplification and Southern blot hybridization, we detected foamy virus DNA only in lymphocytes of two accidentally infected humans and five naturally infected monkeys, as well as in DNA samples from four Graves' disease patients investigated in the French study. However, we failed to detect foamy virus DNA in peripheral blood lymphocytes from any of the 41 Graves' disease patients of the German cohort. Thus, a causative role of foamy viruses in this thyroid disease is highly improbable.

Adult↗

[Thyrotoxic crisis after exposure to iodine. A case with fatal outcome].

A 78-year-old woman is presented with a multinodular toxic goiter and euthyroidism under continuous low-dose treatment with antithyroid drugs. A period of hyperthyroidism had been documented 3 years previously. In the preoperative management, prior to resection of a benign ovarian tumour, an intravenous urogram was performed. Perchlorate was given for thyroid protection. One day after surgery the clinical signs of thyroid storm were observed. Immediately, high-dose antithyroid drug therapy was started. Nevertheless, the patient died of acute cardiovascular failure 3 days later. This case report focuses on the risk of thyroid storm following iodine excess in the presence of relevant functional thyroid autonomy without adequate thyroid protection.

Aged↗

[Rational diagnosis of thyroid gland diseases].

The recommendations for the diagnosis of diseases of the thyroid gland issued seven years ago by the Thyroid Gland Section of the German Society of Endocrinology continue to apply, and are still relevant. On this basis, the main procedures available for effective and rational diagnostic evaluation are discussed. Depending upon the case history and clinical findings, a diagnostic strategy is developed for the most common benign diseases of the thyroid gland.

Diagnostic Imaging↗

Effect of miltefosine on transplanted methylnitrosourea-induced mammary carcinoma growing in Fischer 344 rats.

Miltefosine (hexadecylphosphocholine, HPC, CAS 58066-85-6) was investigated in transplanted primary methylnitrosourea-induced PYH mammary carcinoma of F344 rats. The therapy was performed in the 5th and 10th passage. At first HPC (113 mg/kg body weight) significantly reduced the median tumor volume, but a loss of activity was observed in the 10th passage. To explain the loss of sensitivity and to obtain information on the mechanism of action histology, cytoskeleton and hormone receptor content were investigated. The most important change was observed in the histopathology of the tumor. The initial tubular papillary adenocarcinoma was transformed into a malignant adenoacanthoma with epithelial structure. Vimentin as an endothelial marker of the cytoskeleton was equally expressed in all passages. Cytokeratin was weakly expressed in the earlier passages and intensively present in the late passages. The histopathological change from tubular adenocarcinoma to malignant adenoacanthoma might be caused by an overgrowth of the primary epithelial tumor cells or by a real transformation in the morphological characteristics of the tumor, which may occur during repeated transplantation.

Adenocarcinoma↗

Metabolic design of combination therapy: use of enhanced fluorodeoxyglucose uptake caused by chemotherapy.

In order to quantify effects of an experimental chemotherapy, MCF7 cells were studied with 14C-fluorodeoxyglucose (FDG) and high-performance liquid chromatography (HPLC). Uptake measurements were performed 1 and 4 hr after the end of a therapy with hexadecylphosphocholine (HPC). A dose- and time-dependent increase of the FDG uptake after therapy was observed, with a maximum at 1 hr after therapy. These data were used to develop a new metabolic design of combination treatment. Several time-dose combinations of HPC and deoxyglucose (DOG) were analyzed for their effects on growth inhibition. The combinations using DOG in the period of pronounced enhancement of FDG uptake (1 hr after HPC treatment) were found to be the most effective with an improvement of up to 520% in growth inhibition. This metabolic design of combination treatment may also be applied in vivo, and PET can be used to optimize the time and dose schedule of the modified treatment protocol.

Antineoplastic Agents↗