Biomedical subjects
Publications and source records attributed to H Sitter.
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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.
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.
The perioperative changes in epinephrin-, norepinephrine-, histamin-, C5a- and interleukin-6-levels were studied in 40 patients undergoing cholecystectomy for the diagnosis of acute cholecystitis. All relevant mediator levels could be determined in 38 patients. The outcome was not optimal in 16 of them (42%). In order to evaluate the predictive value of the mediators under investigation for the quality of the patients' outcome, a model based on the Bayes' theorem was developed. Using this model the outcome (optimal vs. not optimal) could be correctly predicted in 30 (79%) of our study patients. This kind of data analysis allows to define states of increased risk for a not optimal recovery based on biochemical parameters.
In clinical reality the drugs used for H1/H2-prophylaxis are not restricted to the combination of dimetinden/cimetidine, also only for this combination the effectiveness for preventing severe cardiorespiratory disturbances is proven in a randomised controlled clinical trial. However, it is almost impossible to conduct such an extended clinical trial in order to check all possible combinations. Instead of this, we developed a complex animal model featuring clinical variability and the principles of a well conducted randomised controlled clinical trial (CMRT = clinic modelling randomised trials), to evaluate different H1/H2 combinations. In this CMRT in pigs (four groups of 15 animals), the H1/H2 combination of dimetinden/cimetidine and dimetinden/famotidine showed an effectiveness similar to the randomised clinical trial. With dimetinden/ranitidine no significant prophylactic effect was observed. Two conclusions can be drawn: (1) CMRTs in animals are able to answer relevant clinical and research questions that otherwise only could be solved by clinical studies and may be a successful intermediate between basic research and clinical trials. (2) Drugs, even of the same substance class, may not be simply exchangeable. Hence, before changing a proven medication, trials in an adequate complex animal model (CMRT) should be mandatory.
BACKGROUND: Ultrasonography (US) by acknowledged experts enhances the diagnostic performance and reduces the rate of negative laparotomies in patients with suspected acute appendicitis (AA). METHODS: The diagnostic accuracy and clinical impact of routine US performed by surgical residents was prospectively studied in 504 unselected patients admitted for AA. Clinical and US findings were correlated with laparotomy findings and pathological outcome in 135 patients (113 cases with proven AA, prevalence 22.4%) and clinical as well as follow-up data were compared in the remainder. RESULTS: The overall accuracy, sensitivity, and specificity of the clinical diagnosis of AA were 84.9%, 51.3%, and 94.6% and those of US were 93. 6%, 83.1%, and 96.6%. Joint evaluation of the results from clinical evaluation and US further improved diagnostic performance (accuracy 93.4%, sensitivity 84.1%, specificity 96.2) and significantly reduced the rate of diagnostic errors to 3.4% (p < 0.001) and unnecessary laparotomies to 9.6% (p < 0.01) in patients with suspected AA. CONCLUSIONS: Ultrasonographic evaluation of the patient with suspected AA is considered to be of value in surgical practice.
BACKGROUND: Recent studies have documented the feasibility of ultrasonography (US) to diagnose acute colonic diverticulitis (ACD). This prospective observational trial determined the sonomorphology of ACD and evaluated the diagnostic accuracy of routine US performed on admission by surgeons in training. METHODS: Fifty-seven consecutive patients with a confirmed episode of ACD were entered into this study, and the sonomorphology of the involved colon was assessed. US findings were compared to the results of the clinical evaluation and correlated to the clinicopathological outcome. RESULTS: The sonomorphology of ACD was characterized by segmental inflammatory transformation of the colon averaging 9.9 +/- 3.2 cm (range, 6-20) in length and visualized as target phenomena of a mean 3.5 +/- 0.8 cm (range, 2.4-4.8) width. Targets were caused by hypoechogenic thickening of the colonic wall of an average 7.7 +/- 2. 6 mm (range, 4-18). In 40% of cases, a hyperechogenic halo representing peridiverticulitis (average width, 2.3 +/- 0.6; range, 1.2-3 cm) was noted. Diverticula were seen in almost half of the cases. Of the 57 cases with confirmed ACD, the diagnosis was made by US in 48, for a global accuracy of 84.2%. US was false negative in nine patients, suggesting perforated appendicitis in five cases and acute appendicitis in one (the final diagnoses were perforated sigmoid diverticulitis in five cases and cecal diverticulitis in one case). In three patients, US was nondiagnostic. CONCLUSION: In the hands of sonographically trained surgeons, ultrasound is a useful modality to image acute colonic diverticulitis. US reveals diagnostic sonomorphology in most cases of ACD and therefore facilitates early confirmation of the diagnosis and assessment of severity.
BACKGROUND: Recent studies suggest a role for somatostatin in the medical treatment of hyperparathyroidism. In a prospective, randomized, controlled, triple blinded clinical trial in patients with primary or secondary hyperparathyroidism, we evaluated the response of biochemical parameters relevant in hyperparathyroidism to the somatostatin analog octreotide. METHODS: Forty patients each with primary or secondary hyperparathyroidism were studied. Among other parameters, serum calcium and serum phosphate, parathyroid hormone, calcitonin, osteocalcin, and octreotide were assessed before and repeatedly for 4 hours after a single intravenous application of 200 micrograms octreotide or placebo. Subsequent to operation, which was performed on all patients, somatostatin-receptor autoradiography of parathyroid tissue was performed. RESULTS: After administration of octreotide, which resulted in an increase of plasma levels to pharmacologic levels, no significant changes in any of the biochemical parameters investigated for were observed. Multivariate analysis did not identify patient subpopulations that responded to either drug or placebo (p > 0.05). Forty-five percent of patients receiving octreotide reported side effects: Parathyroid tissue samples of patients with primary or secondary hyperparathyroidism were negative for somatostatin-receptor expression. CONCLUSIONS: Octreotide has no discernible effect on biochemical parameters of patients with primary or secondary hyperparathyroidism. Absence of somatostatin receptors, together with lack of octreotide effects, suggests that somatostatin is not effective in the medical therapy of hyperparathyroidism.
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BACKGROUND: The clinical diagnosis of acute colonic diverticulitis (ACD) can be difficult and ultrasonography by experts is valuable in establishing the diagnosis. This prospective observational trial aimed to assess the diagnostic accuracy and clinical value of ultrasonography performed routinely by surgical residents in training. METHODS: The clinical course of 187 unselected consecutive patients admitted with suspected ACD was studied prospectively. Patients who had surgery for generalized peritonitis were excluded, leaving 143 for evaluation. Ultrasonographic findings and clinical assessment on admission were correlated with the patient's clinicopathological data and discharge diagnosis respectively. RESULTS: Of 74 patients with proven ACD (prevalence 52 per cent) the diagnosis was made by ultrasonography in 62, with an accuracy of 88 per cent, sensitivity 84 per cent and specificity 93 per cent. Ultrasonography gave a false-negative result in 12 patients (negative predictive value (NPV) 84 per cent) and there were five false-positive findings (positive predictive value (PPV) 93 per cent). The final diagnosis in the latter five patients was colitis (two patients), caecal carcinoma (one), colonic ileus due to perforated sigmoid carcinoma (one) and suppurative pyosalpingitis with involvement of the sigmoid colon (one). The accuracy of clinical evaluation on admission was 71 per cent (sensitivity 82 per cent, specificity 55 per cent, PPV 72 per cent, NPV 68 per cent); however, in only 53 per cent of patients was the diagnosis considered clinically unequivocal. CONCLUSION: Ultrasonography is a useful and valid modality for imaging ACD and its differential diagnoses in the hands of sonographically trained surgeons. It is especially helpful when the clinical findings are equivocal.
Models of evaluation in therapeutic management pathways (practice guidelines, clinical algorithms) are demanded today, both by public health research and health policy. However, practical achievements are lacking. To overcome this controversy, the Lucerne Study Group on Sepsis Research was founded to develop guidelines in accordance with a series of official groups. It was shown that there was no agreement between the providers and the daily users. However, every surgeon has a firm, personal view about sepsis.
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OBJECTIVE: To evaluate preoperative and operative methods of detecting liver metastases in patients undergoing primary resection for colorectal carcinoma. DESIGN: Prospective, open study. SETTING: Teaching hospital, Germany. SUBJECTS: 51 Patients with confirmed primary colorectal carcinoma. INTERVENTIONS: Computed tomography during arterial portography (CT-AP), percutaneous ultrasonography (US), operative palpation and examination of the liver, operative US, and computed tomography (CT) follow-up 6-12 months postoperatively. MAIN OUTCOME MEASURES: Sensitivity, specificity, positive and negative predictive value, and accuracy. RESULTS: Overall accuracy was worst for CT during portography, because of the diagnosis of many false positive lesions. Exploration and palpation of the liver had the highest sensitivity (83%) and specificity (100%), and operative US did not give any useful additional information. CONCLUSIONS: Preoperative percutaneous US is recommended as the best non-invasive screening test; otherwise careful inspection and palpation during operation are sufficient for the evaluation of the liver during primary resection for colorectal carcinoma.
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OBJECTIVE: To assess a new technique of anatomically precise hepatic segmental resection and to compare the degree of precision and biochemical profiles with results after traditional segmental resection and a sham operation. DESIGN: Experimental study. SETTING: University hospital, Germany. MATERIAL: 50 sheep (10 each had segments II, III, and IV removed by the new technique, and 10 each were studied in the traditional resection and sham operated groups). INTERVENTIONS: Operative ultrasonography and injection of methylene blue to identify segmental boundaries. In traditional operations boundaries were identified only from knowledge of the surface structure of the liver. MAIN OUTCOME MEASURES: Degree of precision, duration of operation, blood loss, mortality, transaminase activities and liver function tests. RESULTS: Anatomically precise segmentectomies were achieved in 6/9 (67%) for segment II, 6/9 (67%) for segment III, and 4/8 (50%) for segment IV. Using the traditional technique (segment III only) there was only 1/10 anatomically precise resections, together with 5 perisegmentectomies and 4 incomplete resections (p < 0.02). The operations for anatomically precise resection lasted significantly longer, but resection time was similar. Blood loss, survival, and transaminase activities were similar for the two groups, but the margin of necrosis at the cut edge was significantly less in anatomically precise resections. CONCLUSION: Anatomically precise hepatic resections are technically feasible with the use of intraoperative ultrasonography and selective staining of the segment(s) to be removed with methylene blue. Although it takes longer, there are no detrimental consequences compared with the considerably less accurate traditional technique.
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Although histamine release is recognised as a common event during anaesthesia and surgery, few clinicians judge the resultant cardiorespiratory disturbances serious enough to warrant prophylaxis with antihistamines. We have assessed the incidence and importance of histamine release in a randomised 2 x 2 factorial study. 240 patients representing a routine throughput of major general surgery were studied during a standardised induction of anaesthesia and preoperative loading of the circulation with either Ringer solution or Haemaccel-35, with or without antihistamine prophylaxis with dimetindene (H1) plus cimetidine (H2). Cardiorespiratory disturbances were graded as detectable, clinically relevant, or life-threatening from observers' records of the anaesthesia and the actions taken by the anaesthetists. Disturbances that were accompanied by significant rises in plasma histamine were further designated histamine-related, and those that were not were designated histamine-unrelated. Anaesthetists, observers, and designators were blinded to whether or not the patients had received antihistamines and to which solution was used for circulatory volume loading. Clinically relevant or life-threatening histamine-related disturbances occurred in 8% of the patients who after induction of anaesthesia received Ringer without antihistamines, in 26% of those who received Haemaccel without antihistamines, and in 2% or less of those who received antihistamines (p < or = 0.0001). There were 4 life-threatening histamine-related disturbances, all in patients who received Haemaccel without antihistamines (p < 0.01). Histamine-unrelated disturbances occurred in 16% overall, with no obvious effect of Haemaccel or antihistamines. The histamine-related disturbances under anaesthesia were remarkable for their severity (even with small rises in histamine concentrations), for the prevalence of bradycardia, and for the absence of skin signs. Their likelihood and severity were increased in patients with tumours. The results of the trial make a case for routine prophylaxis with antihistamines as part of anaesthetic management.