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Biomedical subjects

A Zielke

Publications and source records attributed to A Zielke.

At least 37 records · Page 2Linked to original sources
PubMed2004

Medical and surgical treatment for secondary and tertiary hyperparathyroidism.

Prevention and treatment of secondary hyperparathyroidism (SHPT) in patients on chronic maintenance hemodialysis and of tertiary hyperparathyroidism (THPT) in patients after kidney transplantation is a challenge for the nephrologist and for the surgeon. Indication and results of medical and surgical therapy for SHPT and THPT have remained under discussion during the last decades. This review resumes the current medical and surgical strategies for patients with SHPT and THPT.

Bone and Bones↗
PubMed2003

Diagnostic score in appendicitis. Validation of a diagnostic score (Eskelinen score) in patients in whom acute appendicitis is suspected.

BACKGROUND AND AIM: At times, the diagnosis of acute appendicitis may be difficult. However, for minimum morbidity to be obtained, early and accurate diagnosis is essential. This study aimed to validate a scoring system proposed by Eskelinen et al. as an aid in making the diagnosis of appendicitis. PATIENTS AND METHODS: The prospectively documented data of a consecutive series of 2,359 patients admitted for suspicion of appendicitis were used for validation. Accuracy and positive predictive value were defined as the main overall performance parameters, as was the rate of unnecessary operations to assess changes of patient management. Overall performance was assessed by receiver-operator characteristics (ROC) analysis. RESULTS: Of 2,359 patients, 662 were proven to have acute appendicitis (prevalence of 28%). The overall sensitivity, specificity, positive and negative predictive value, and accuracy of the score were 0.79, 0.85, 0.68, 0.91 and 0.835 at a cut-off value of 55. Calibration of the score's cut-off value to 57 yielded more favourable results (0.72, 0.91, 0.76, 0.9 and 0.86), and the rate of unnecessary operations declined from 26.6% to 15.4% ( P<0.05, chi2). ROC analysis revealed an area index of 0.91. CONCLUSION: The Eskelinen score delivered acceptable clinical results only after calibration to a cut-off value of 57. The data from this study suggest the investigation of whether a calibrated score might be particularly instrumental in the pre-admission evaluation of the patient in whom appendicitis is suspected.

Acute Disease↗
PubMed2002

[Appendicitis. Present-day diagnosis].

At times, making the diagnosis of acute appendicitis may pose a considerable problem. However, prompt and accurate diagnosis is essential to obtain minimal morbidity. Diagnostic mistakes result either in delayed initiation of adequate therapy or unnecessary operations. During the past years, a number of new strategies and diagnostic procedures have been developed and refined, including structured patient interview pathways, scoring systems, ultrasound, computed tomography, and diagnostic laparoscopy. This review summarizes the diagnostic performance of these modalities and discusses their clinical impact. It is apparent that in everyday practice, none of the technical modalities can replace the skill and precision of surgical exploration.

Acute Disease↗
PubMed2002

In vitro and in vivo angiogenesis in PC12 pheochromocytoma cells is mediated by vascular endothelial growth factor.

Angiogenesis, the formation of new blood vessels from existing vascular endothelium, is essential for tumor growth. Vascular endothelial growth factor (VEGF) is an endotheliumspecific mitogen and regulator of angiogenesis. Angiogenesis has been associated to the malignant phenotype of pheochromocytomas and is readily observed in experimental pheochromocytomas. Although VEGF gene expression has already been demonstrated in the rat PC12 cell line, the detailed mechanisms of action are not known. We have, therefore, studied angiogenesis in the rat PC12 pheochromocytoma cell line in vitro and in vivo. VEGF gene expression and accumulation of VEGF protein in cytoplasm and conditioned medium of PC12 cells was found. Conditioned medium from PC12 cells significantly increased proliferation of VEGF-dependent endothelial cells from human umbilical veins, and this effect reversed upon addition of a neutralizing anti-VEGF antibody. Dexamethasone and nerve growth factor (NGF) increased VEGF mRNA expression and accumulation of VEGF protein of PC12 subclones with established metastatic activity in vivo. PC12 cells xenotransplanted to nude mice had marked VEGF expression and induced host angiogenesis, confirmed by the presence of CD34-positive endothelial cells in the experimental PC12 tumors. When NGF-primed PC12 cells were immobilized in Matrigel supplemented with rising concentrations of the growth factor and xenotransplanted, increasing NGF resulted in tumors with smaller areas of necrosis and increased vital tumor volume. These results suggest that VEGF is a mediator of angiogenesis in the PC12 pheochromocytoma cell line, and that dexamethasone and NGF affect VEGF expression. Our data further suggest that NGF may contribute to angiogenesis in experimental pheochromocytoma.

Adrenal Gland Neoplasms↗
PubMed2001

Feasibility of MRI in the diagnosis of acute diverticulitis: initial results.

PURPOSE: The purpose of this study was to evaluate MRI as a diagnostic tool in patients with suspected acute sigmoid diverticulitis. Furthermore, we sought to develop an optimal imaging protocol in these patients. PATIENTS AND METHODS: Eleven patients with suspected acute diverticulitis were included in the study. All patients were imaged in a 1.0 T clinical scanner using a body-array coil. Imaging sequences were single-shot TSE, HASTE-, STIR- and TrueFisp- sequence. All were obtained in the frontal plane. The diagnosis was verified by a single experienced investigator, using ultrasound, and overall clinicopathological outcome. RESULTS: MRI enabled visualization of signs of an acute diverticulitis in all patients. However, the diagnosis of acute diverticulitis was obtained in 10 patients only. The mean imaging time was 17.5+/-5.5 min. STIR- and TrueFisp-sequences alone displayed all findings, e.g pericolonic exsudation, edema and segmental narrowing, whereas SSTSE and HASTE-sequences showed no additional information. Therefore, it appeared that the imaging protocol could be restricted to STIR- and TrueFisp-sequences. CONCLUSION: MRI is feasible as a fast, accurate and investigator-independent diagnostic tool in patients with suspected acute diverticulitis. To prove its value in comparison to computed tomography or ultrasound, further studies are needed.

Acute Disease↗
PubMed2001

Clinical decision-making, ultrasonography, and scores for evaluation of suspected acute appendicitis.

Diagnosing acute appendicitis (aA) remains difficult. This study evaluated the utility of ultrasonography (US) compared to clinical decision-making alone and scoring systems to establish the indication for laparotomy in patients in whom aA was suspected. The prospectively documented data of 2209 patients admitted for suspicion of aA, who underwent US by one of 12 surgeons, formed a database in which the diagnostic and procedural performance of clinical decision-making, US, two scoring systems (Ohmann and Eskelinen scores), and clinical algorithms taking account of clinical and either US findings or score results, were retrospectively evaluated. The results of either modality were correlated with final diagnoses obtained by laparotomy in 696 patients, of whom 540 had aA (prevalence 24.45%) and follow-up data in the remainder. US had the highest specificity (97%, compared to 93% for the Ohmann and Eskelinen scores and 94% for the clinical evaluation and algorithms) and lowest overall rate of false-positive findings (negative laparotomy rate 7.6%). The scores were accurate in refuting the diagnosis of aA but otherwise not superior to US. The best overall diagnostic and procedural results were obtained with the algorithms that combined the results of either US or the Ohmann score with clinical evaluation, which produced the most favorable numbers of negative laparotomies, potential perforations, and missed cases of aA. US is the diagnostic standard of reference for patients with a possible diagnosis of aA. It yields diagnostic results superior to those of scoring systems and provisional clinical evaluation. However, the benefits of US by ultrasonographically trained surgeons are only fully appreciated within the context of clinical algorithms. The joint evaluation of score results and clinical evaluation may deliver information of similar accuracy.

Acute Disease↗
PubMed2001

Acute colonic diverticulitis: visualization in magnetic resonance imaging.

The incidence of acute colonic diverticulitis (ACD) is increasing. To allow rational therapeutic decisions to be made, a timely diagnosis is required. The feasibility of "on-admission-MRI" to establish the diagnosis has not yet been studied. Therefore, a prospective observational study was carried out in 20 patients with an established diagnosis of ACD. The diagnostic criteria for the MRI diagnosis of ACD were the demonstration of at least one diverticulum, pericolic exudation, and edema of the colonic wall. MRI was diagnostic in all but one patient. It is concluded that MRI has considerable diagnostic potential in ACD and should be formally evaluated.

Acute Disease↗
PubMed2000

How asymptomatic is asymptomatic primary hyperparathyroidism?

We observed several cases of patients who believed they were free of symptoms or signs of primary hyperparathyroidism (pHPT) preoperatively. reported a change of complaints following parathyroidectomy (PTX). We, therefore, decided to examine a larger group of patients to discover if these findings were incidental or of more general significance. The role of PTX in these patients with asymptomatic pHPT remains controversial. In 1991 criteria were defined at a NIH-consensus conference, according to which patients qualify for either operative therapy or long term medical surveillance. Until now, it was generally believed that the majority of asymptomatic patients would never develop symptoms. In a epidemiological cohort-study, the perioperative data of 582 consecutive patients with pHPT, including 116 asymptomatic patients (20.9%), who underwent parathyroidectomy between 1987 and 1998 were evaluated by uni- and multivariate analysis. At a median of 72 months postoperatively, all patients underwent a planned follow-up which included a standardised, validated questionnaire, physical examination and laboratory investigations. Eighty-six patients who were asymptomatic preoperatively were available for follow-up. Only eight (9.3%) were definitely asymptomatic, 4.6% of the entire, representative cohort. Postoperative improvement was reported in 81.4% of the "asymptomatic" patients. Multivariate analysis did not reveal a single or a set of preoperative measurements, that would allow to predict the retrospectively definitely asymptomatic patient. PTX resulted in normocalcaemia in 98.8% of preoperatively asymptomatic patients, with an operative morbidity of 1.2% and no mortality. Many apparently asymptomatic patients with pHPT will only realise that they did in fact have preoperative symptoms in retrospect, following PTX. This study suggests that using an up-to-date definition of asymptomatic pHPT, there are only a small number of truly asymptomatic patients and that these cannot be predicted preoperatively, as their symptoms may become apparent only after PTX. "Asymptomatic" patients with pHPT may share the same objective and subjective benefits from PTX as symptomatic patients. They should be operated as soon as the diagnosis is established.

Calcium↗
PubMed1999

[Can diagnostic scoring systems help decision making in primary care of patients with suspected acute appendicitis?].

BACKGROUND AND OBJECTIVE: To assess two recently developed scoring systems with respect to making or excluding the diagnosis of acute appendicitis. PATIENTS AND METHODS: Data on 2359 patients with typical signs of acute appendicitis (AA) were analysed, the results of two diagnostic scoring systems being compared with the diagnosis made by an experienced surgeon. RESULTS: AA was confirmed in 662 of the 22,359 patients (prevalence 28%). Sensitivity, specificity, positive and negative predictive values and overall accuracy for diagnosis with the Ohmann scoring system were 0.63, 0.93, 0.77, 0.86 and 0.84; with the Eskelinen score the values were 0.79, 0.85, 0.68, 0.81 and 0.835; and by the surgeon they were 0.90, 0.94, 0.85, 0.96 und 0.93. The negative appendectomy or laparotomy rate was 14.3 an 12.3 respectively with the Ohmann score, 29.5 and 26.6 with the Eskelinen score. The numbers of potential and of nondiagnosed perforations were 41% and 37% respectively with the Ohman score and 26.6% and 16.3% with the Eskelinen score. The number of missed cases of AA was lowest with the Ohman scoring system, compared with 1.8% for the surgeon. After excluding AA, both scoring systems had a specificity of -0.99, with a positive probability rate of at least 27 (Eskelinen score) up to 87 (Ohman score). CONCLUSION: Both diagnostic scoring systems are better for excluding than correctly diagnosing AA; the decision to exclude could be made with a high degree of accuracy. Either scoring system may therefore be used in primary care of patients suspected of AA to help decide on referral to hospital.

Acute Disease↗
PubMed1999

[Validation of a diagnostic scoring system (Ohmann score) in acute appendicitis].

A diagnostic scoring system, recently published by Ohmann et al. in this journal, was validated by analyzing the clinicopathological data of a consecutive series of 2,359 patients, admitted for suspicion of acute appendicitis. The results of the scoring system were compared to the results of clinical evaluation by junior (provisional) and senior surgeons (final clinical diagnosis). To assess the diagnostic ability of the score, the accuracy and positive predictive value were defined as the major diagnostic performance parameters; the rate of theoretical negative laparotomies and that of diagnostic errors served as the major procedural performance parameters. Of 2,359 patients admitted for suspected acute appendicitis, 662 were proven to have acute appendicitis by histology, for a prevalence of 28%. The overall sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of the provisional clinical diagnosis were 0.50, 0.94, 0.77, 0.83, and 0.82; 0.93, for the score 0.63, 0.93, 0.77, 0.86 and 0.84, and for the final clinical diagnosis 0.90, 0.94, 0.85, 0.96, and 0.93, respectively. Of the main diagnostic performance parameter, the accuracy of the score was significantly better than that of provisional clinical diagnosis (P < 0.05, chi 2 test). The score yielded a rate of negative appendecomies and laparotomies of 14.3 and 12.3%. With respect to the rate of overlooked cases of acute apendicitis, the score demonstrated a superior performance, with only 6 cases missed (0.9%). However, the number of patients with acute appendicitis, including those with perforated disease, who were not identified by the score, was almost four times that of the final clinical diagnosis (245 vs 63). With regard to the main procedural performance parameter, the score resulted in a significantly smaller number of diagnostic errors than the provisional clinical investigator (P < 0.05, chi 2 test). The results of this study indicate that the diagnostic scoring system might be helpful when experienced investigators or additional diagnostic modalities such as ultrasonography are not available. It may therefore be of value in the preclinical evaluation of patients with suspected acute appendicitis and may be instrumental as a quality control tool and in clinical guidelines.

Acute Disease↗
PubMed1999

[Formal decision aids in surgery--results of a survey].

Even though many decision-aids have been developed in the past, the application of these systems in clinical practice is still rare. There are many reasons for this, including the reservations of potential users. A survey in three university surgery clinics was conducted to assess the experience and attitudes towards decision-aids among physicians. Seventy-two of the 102 physicians approached (71%) filled out and returned the short questionnaire that was sent to them. More than half of the 72 survey participants already use decision-aids. Among them, guidelines are used most often (46%), whereas other instruments (algorithms, scores, decision trees) are used less frequently (10-17%). Computer-based decision-aids are hardly used at all (7%). These results are in contrast to the strong request for more decision-aids, especially for computer-based systems (40%). Physicians who already use decision-aids are more interested in additional systems. More than 70% of all participants are interested in more information about the topic. The standardized question about attitudes towards computer-based decision-aids reveals more positive than negative appraisal, whereas the answers to open questions focus more on objections. The substantial differences between the three survey locations in parts of the survey results show that attitudes towards decision-aids are influenced by the way the instruments are introduced and the way the users are informed and involved in the process of implementation. A successful implementation of decision-aids in clinical practice should therefore try to integrate the future users as much as possible.

Academic Medical Centers↗
PubMed1999

Pleiotropic effects of thyroid stimulating hormone in a differentiated thyroid cancer cell line. Studies on proliferation, thyroglobulin secretion, adhesion, migration and invasion.

Thyroid stimulating hormone (TSH) causes differentiation and epidermal growth factor (EGF) causes dedifferentiation of thyroid cells in vitro. In undifferentiated thyroid cancer cell lines, TSH stimulates tumor cell migration and invasion, a dedifferentiated function, presumably due to an escape of tumor cells from the control of differentiating growth factors. In a highly differentiated thyroid carcinoma cell line of Hürthle cell origin (XTC), we tested the hypothesis that TSH would stimulate thyroglobulin secretion (a differentiated function) more than EGF, and EGF would stimulate invasion (a de-differentiated function) more than TSH. Proliferation, adhesion, cell migration and invasion were measured by the MTT assay, human thyroglobulin by RIA and protease activity by substrate-gel zymography. TSH induced differentiated morphologic changes in XTC cells and stimulated secretion of human thyroglobulin in a dose dependent manner, whereas EGF did not. The effects of TSH on growth, adhesion, migration and invasion were dose dependent and biphasic, with an increase at low and a decrease at high concentrations of TSH. These effects were always more pronounced than those observed with EGE Gelatinolytic activity, consistent with metalloproteinase activity was revealed by zymography, but the pattern of secretion was not altered by neither TSH nor EGF. These results suggest, that TSH has pleiotropic effects on differentiated thyroid cancer cells in vitro that involve differentiated morphology and function but also affect features commonly associated with the malignant in vitro phenotype.

Cell Adhesion↗
PubMed1998

[Postoperative complications and long-term results of the surgical treatment of immunogenic Basedow's disease].

BACKGROUND AND OBJECTIVE: The surgical options for immunogenic Grave's disease (hyperthyroidism with ophthalmopathy) are not uniform. This study was undertaken to compare the effectiveness of several types of operation. PATIENTS AND METHODS: In a retrospective study the data on 99 patients with Grave's disease (aged 10 to 71 years, mean 35 years), operated on from 1987 to 1996 by 28 different surgeons, were analysed. Follow-up examinations were then undertaken a mean of 42 months (range of 12-108 months) postoperatively. RESULTS: Bilateral subtotal thyroid resection had been performed in 45 patients, unilateral subtotal resection with contralateral hemithyroidectomy in 49 and total thyroidectomy in five. Re-operation for postoperative bleeding was necessary in three patients. At follow-up two patients were found to have recurrent nerve palsy. Four patients had to be treated for mild chronic hyperparathyroidism. There was no significant difference between the different operation regarding type and frequency of complications. At following-up examination none of the patients had hyperthyroidism. 37 of 50 patients with endocrine ophthalmopathy were improved after the operation. CONCLUSIONS: With a standardized operative technique and retention of less than 6 g of thyroid tissue a recurrence of hyperthyroidism can be reliably prevented. This form of treatment can be achieved with an acceptable complication rate, which is unrelated to the type of operation.

Adolescent↗
PubMed1998

Amitogenic alginates: key to first clinical application of microencapsulation technology.

Microencapsulation refers to a technique of immunoisolation by coating single cells or tissue with a semipermeable membrane. By combining microencapsulation with a specific tissue culturing method, iso-, allo-, and xenotransplantation of parathyroid tissue has been achieved without immunosuppression in a long-term animal model. Prior to its clinical use, continued analyses of the alginate, used as a coating substance, determined its mitogenic properties. Purification of the commercially available alginate was achieved using patented electrophoretic procedures, resulting in an amitogenic alginate suitable for use in humans. However, this alginate exhibited entirely different physical properties. We have recently shown that isotransplanted parathyroid tissue remains vital and functioning in vivo over long periods of time using the novel amitogenic alginate. It is essential to document, whether the alginate is able to maintain immunoisolation. We have therefore assessed its in vivo function compared to the mitogenic alginate in a transgenic animal model. Altogether 600 parathyroid glands from 300 Lewis rats (donor animals) were excised and subjected to tissue culture. Thereafter they were allotransplanted to 30 parathyroidectomized Dark-Auita rats, microencapsulated with the amitogenic or the mitogenic alginate or naked, with 10 recipient animals in each group. Total serum calcium and parathyroid hormone levels were monitored continuously at weekly intervals for 30 weeks. After 26 weeks the transplant beds were excised and subjected to histologic examination. More than 6 months after allotransplantation 9 of 10 animals that had received amitogenic transplants, compared to 7 of 10 animals in the group with mitogenic microcapsules were normocalcemic. Animals that had received naked parathyroid tissue were hypocalcemic as soon as 2 weeks after allotransplantation. Correspondingly, normocalcemic animals showed vital parathyroid tissue inside the microcapsules, which were surrounded by a significantly smaller rim of fibroblasts when amitogenic alginate had been used. In addition to confirming physiologic long-term function, we were able to document for the first time that immunoisolation can also be achieved with the novel amitogenic alginate, which is suitable for clinical use.

Alginates↗
PubMed1998

Hepatic-portal venous gas in acute colonic diverticulitis.

The diagnosis and assessment of severity of acute colonic diverticulitis may be difficult. A case is presented, in which the delayed diagnosis of diverticulitis resulted in the development of a diverticular mesocolic abscess complicated by hepatic-portal venous gas (HPVG). The utility of ultrasound as a rapid, noninvasive tool to diagnose this distinctly rare condition is outlined. The literature on HPVG associated with acute colonic diverticulitis is reviewed, and the therapeutic options are discussed.

Abscess↗
PubMed1998

A unique allogenic model of metastatic pheochromocytoma: PC12 rat pheochromocytoma xenografts to nude mice and establishment of metastases-derived PC12 variants.

Local invasion and metastatic spread to distant sites are major causes of death in patients with malignant pheochromocytoma. Since appropriate in vivo models do not exist, little is known about the underlying mechanisms of tumor growth and invasion. We, therefore, developed an animal model of malignant pheochromocytoma and established organotropic metastatic variants of PC12 rat pheochromocytoma cells. PC12 cells were established as xenografts to BALB/c NCR-NU mice. Subsequent to development of tumors or metastases, primary cultures from local tumors, metastases to lymph nodes, lungs and liver were established. These were subcultured in vitro and reinjected for up to five successive in vivo/in vitro cycles. Xenografted PC12 cells grew tumors with a doubling time of 6.78 +/- 0.58 days during log phase of tumor growth, killing hosts within 5-12 weeks depending on the experimental conditions. Tumors reproducibly metastasized to lymph nodes and the lung. Spontaneous metastases to the liver were not observed, but were achieved by intrasplenic injection of parent PC12 cells. In vitro, the metastatic cell lines displayed striking differences in morphology, overall growth patterns and nutritional requirements as well as binding to purified extracellular matrix proteins compared to the parent cell line. In vivo, the metastatic variants showed marked enhancement of metastatic ability. This is the first report of PC12 rat pheochromocytoma cells to exhibit the malignant phenotype in vivo. We also established variant PC12 cell lines that preferentially metastasized to specific sites and that had acquired different in vitro behavior and ability to metastasize. This unique model system should be useful for further studies relating to the invasion and metastases of pheochromocytoma and may prove valuable for investigations of novel antineoplastic therapies in vitro and in vivo.

Animals↗
PubMed1998

Influence of ultrasound on clinical decision making in acute appendicitis: a prospective study.

OBJECTIVE: To assess the efficacy of ultrasound (US) as part of an algorithm to establish the indication for laparotomy in patients with suspected acute appendicitis. DESIGN: Prospective investigation. SETTING: University department of surgery, Germany. SUBJECTS: 669 unselected patients admitted with suspected acute appendicitis. INTERVENTIONS: Clinicopathological and procedural diagnoses of the algorithm were evaluated by correlating clinical and US findings with the results of laparotomy in 171 patients of whom 143 had acute appendicitis (prevalence 21%), and clinical as well as follow up data in the remainder. MAIN OUTCOME MEASURES: The major clinicopathological variables were accuracy and positive predictive value; the rate of negative laparotomies and that of bad diagnostic errors served as the main procedural variables. RESULTS: The overall sensitivity, specificity, and accuracy of the clinical diagnosis were 0.503, 0.950, and 0.855, respectively (positive predictive value: PPV 0.734, negative predictive value: NPV 0.875), those of ultrasound: 0.797, 0.967, and 0.931 (PPV 0.870, NPV 0.946); and 0.853, 0.927, and 0.940 at the end of the algorithm (PPV 0.762, NPV 0.958). However, the algorithm would have resulted in a significant increase in the rate of unnecessary laparotomies (from 13% to 16%). A revised clinical algorithm gave an overall diagnostic accuracy of 0.940 (p < 0.001) together with a low rate of negative laparotomies (11%, p < 0.01) and a significantly reduced number of diagnostic errors (from 71 to 21, p < 0.001). CONCLUSION: Ultrasonography enabled us to diagnose acute appendicitis in more patients more often and more quickly than clinical evaluation alone, suggesting that US may produce a better outcome. The revised clinical algorithm may be helpful in the study of US in patients with suspected acute appendicitis in prospective randomised controlled clinical trials.

Acute Disease↗