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Biomedical subjects

J Kotzerke

Publications and source records attributed to J Kotzerke.

At least 73 records · Page 4Linked to original sources

Mutations of the ret protooncogene in German multiple endocrine neoplasia families: relation between genotype and phenotype. German Medullary Thyroid Carcinoma Study Group.

It has been suggested that not only the position but also the nature of the mutations of the ret protooncogene strongly correlate with the clinical manifestation of the multiple endocrine neoplasm type 2 (MEN 2) syndrome. In particular, individuals with a Cys634-Arg substitution should have a greater risk of developing parathyroid disease. We, therefore, analyzed 94 unrelated families from Germany with inherited medullary thyroid carcinoma (MTC) for mutation of the ret protooncogene. In all but 1 of 59 families with MEN 2A, germline mutations in the extracellular domain of the ret protein were found. Some 81% of the MEN 2A mutations affected codon 634. Phenotype-genotype correlations suggested that the prevalence of pheochromocytoma and hyperparathyroidism is significantly higher in families with codon 634 mutations, but there was no correlation with the nature of the mutation. In all but 1 of 27 familial MTC (FMTC) families, mutations were detected in 1 of 4 cysteines in the extracellular domain of the ret protooncogene. Half of the FMTC mutations affected codon 634. Mutations outside of codon 634 occurred more often in FMTC families than in MEN 2A families. In all but 1 of 8 MEN 2B patients, de novo mutations in codon 918 were found. These data confirm the preferential localization of MEN 2-associated mutations and the correlation between disease phenotype and the position of the ret mutation, but there was no correlation between the occurrence of hyperparathyroidism or pheochromocytoma and the nature of the mutation.

Amino Acid Sequence↗

[Positron emission tomography in diagnosis of renal cell carcinoma].

PET is a new method for staging malignant tumors; the metabolism is examined and not the morphology. In this study the staging of renal cell carcinoma (RCC) by PET was investigated. In 29 patients PET with fluorodeoxyglucose (FDG) was carried out preoperatively; the PET results were compared to the histology of the OR specimen. In 26 patients a RCC was found histologically, which was diagnosed correctly by PET in 20 patients; in 6 patients a false-negative PET result was obtained. An angiomyolipoma, a pericytoma and a pheochromocytoma showed a false-positive PET result. For lymph-node staging positive nodes were found in 3 patients which was correct; no false-negative result was obtained. In 25 patients the PET result was true-positive; once a false-positive finding occurred. In conclusion, PET offers the advantage that no allergy to FDG is known and a pacemaker or metal implants are not contraindications; in diagnosing RCC, according to our results there is no further advantage of FDG-PET in comparison to standard methods; for lymph-node staging the results are equivalent

Blood Glucose↗

A compartmental model for alveolar clearance of pertechnegas.

UNLABELLED: The washout of an inhaled water soluble radiotracer from the lungs is a measure of alveolar integrity. Data evaluation of 99mTc-DTPA studies were previously performed mainly with monoexponential fitting with or without background subtraction. The introduction of 99mTc-pertechnegas for the assessment of alveolar permeability necessitates the investigation of adequate data evaluation schemes for this radiotracer. METHODS: We developed a three-compartmental model to describe 99mTc-pertechnegas kinetics after inhalation. Monoexponential fitting of the first 5 min was investigated as simplification for clinical use. Different background corrections based on blood samples or representative regions of interest were compared. RESULTS: Correction of intra- and extravascular background by subtraction of calibrated curves, which are derived from blood or background areas, resulted in monoexponential washout curves. Clearance rates based on the three-compartmental model were nearly the same as those derived from a monoexponential fit after blood-activity subtraction (r = 0.96). A monoexponential analysis of the first 5 min without any background correction correlates well with the first component of the biexponential analysis (r = 0.97). CONCLUSION: A dynamic study of more than 45 min allows quantitative determination of the transfer rate of 99mTc-pertechnegas from the alveoli into the blood using compartmental analysis. A simplified monoexponential analysis of the first 5 min allows assessment of lung clearance without any background correction.

Administration, Inhalation↗

Compartment-oriented microdissection of regional lymph nodes in medullary thyroid carcinoma.

Lymph node metastases have been proven to be the main prognostic factor in medullary thyroid carcinoma (MTC). This retrospective study was undertaken to evaluate the efficiency of two surgical techniques of regional lymph node dissection with regard to the normalization of pentagastrin-stimulated serum calcitonin level and patient survival: selective lymphadenectomy, i.e., the excision of macroscopically or microscopically involved lymph nodes, versus a systematic lymphadenectomy performed by the new technique of a compartment-oriented microdissection. From 1970 to 1990, 82 patients with sporadic (n = 57) and hereditary (n = 25) MTC underwent a total of 142 operations including 63 selective lymphadenectomies and, since 1986, 35 systematic lymphadenectomies. The study revealed that in node-positive MTC the rate of interventions with a postoperative normalization of pentagastrin-stimulated serum calcitonin was higher after systematic lymphadenectomy (29.2%) than after selective lymphadenectomy (8.5%) (P < 0.01). The rate of patients undergoing repeat surgery due to a recurrence of MTC was 48% after selective lymphadenectomy and 10% after systematic lymphadenectomy. Survival was significantly better for patients after systematic versus selective lymphadenectomy (P < 0.005). This study thus emphasizes that systematic lymphadenectomy, using the technique of a compartment-oriented microdissection of cervicomediastinal lymph nodes, represents the preferred surgical treatment as well as the optimum technique in primary as well as secondary node-positive MTC.

Adolescent↗

Improvement of tracheal autograft revascularization by means of fibroblast growth factor.

Ischemic airway complications after lung transplantation remain a significant problem despite the use of bronchial omentopexy. Clinical observations suggest that enhancement of vascular ingrowth could possibly increase the efficacy of a bronchial omental flap. This study was therefore designed to investigate whether basic fibroblast growth factor can enhance blood supply of an ischemic airway by acceleration of vascular ingrowth in a rabbit autotransplant model. Segments of the trachea were harvested and transplanted into a subcutaneous pouch. The animals were randomly assigned to one of four groups: group I, no omentopexy; group II, omentopexy; group III, omentopexy and fibrin glue; or group IV, omentopexy and fibrin glue enriched with 2.5 micrograms basic fibroblast growth factor. After 14 days the animals were sacrificed. The extent of perfusion was investigated by means of radioactive microspheres. The morphology of the tracheal segments was investigated in a blinded fashion macroscopically, by means of light microscopy, and by means of scanning electron microscopy. The radioactivity measurements revealed a significantly increased perfusion of group IV (77% +/- 42%) as compared with groups I (17% +/- 13%) and III (20% +/- 16%). By macroscopic and light microscopic assessment, the epithelial integrity of group IV was significantly improved compared with groups I and II. At electron microscopy the integrity of group IV was significantly superior to all remaining groups. We conclude that a deposit of basic fibroblast growth factor and fibrin glue appears to increase revascularization of an ischemic airway from omentum and thus results in improved epithelial preservation of a tracheal autograft.

Animals↗

Improving the accuracy of 99Tcm-mercaptoacetyltriglycine clearance by using two blood samples instead of one? Paediatric Task Group of the EANM.

From a database of 133 patients (98 children and 35 adults) who underwent multiple blood sampling for 99Tcm-mercaptoacetyltriglycine (MAG3) clearance, we determined simplified algorithms allowing the estimation of clearance. A one-compartment model with two blood samples was applied. The best choices for the adult population were the 12 and 90 min blood samples, giving a standard error of the estimate (S.E.E.) of less than 10 ml min-1 1.73 m-2; for the children, the 10 and 80 min blood samples gave a S.E.E. of 20 ml min-1 1.73 m-2; for both the adults and the children, the 10 and 70 min blood samples gave the best results with, however, a S.E.E. of 19 ml min-1 1.73 m-2. The use of such a combined algorithm will therefore result in a degradation of the results in adults, suggesting that a separate algorithm for each group is preferable. We compared the accuracy of the two blood sample method to the one blood sample method based on previously published algorithms for children and adults, respectively. The S.E.E. was significantly lower, in adults as well as in children, using the empirical two blood sample method. This two blood sample method seems potentially useful for routine practice in adult patients. The advantages of using such a method in children is balanced by the practical problems inherent in the need to take a second blood sample during the first 10 min, at a time when the plasma activity is rapidly decreasing.

Adult↗

Determination of the technetium-99m mercaptoacetyltriglycine plasma clearance in children by means of a single blood sample: a multicentre study. The Paediatric Task Group of the EANM.

A multicentre European study was undertaken in order to determine a reasonable algorithm allowing the determination of overall technetium-99m mercaptoacetyltriglycine clearance using a single blood sample. Employing multiple blood sample clearance as a reference method, it was shown that an acceptable estimation of the MAG3 renal clearance could be obtained using a blood sample taken at any time between 30 and 40 min after tracer injection. After correction for body surface area, comparison of clearance determined using (a) the single blood sample and (b) the multiple blood samples provided a coefficient of correlation of 0.949 and an SEE of 27 ml/min. This algorithm is valid for clearance values higher than 100 ml/min/1.73 m2 and for children older than 1 year of age.

Algorithms↗

Prognostic factors in medullary thyroid carcinoma: evaluation of 741 patients from the German Medullary Thyroid Carcinoma Register.

A retrospective study of 741 patients with medullary thyroid carcinoma diagnosed between 1967 and 1991 was carried out by members of the German Medullary Thyroid Carcinoma Study Group to evaluate prognostic factors. A total of 559 patients (75%) were considered to have sporadic disease, and 182 (25%) had the familial type. The sex ratio (male to female) was 1:1.4 in sporadic disease patients, and the mean age at diagnosis was 45.9 years (range 5-81 years). For familial disease patients the sex ratio was 1:1.1, and the mean age at diagnosis was 33.4 (range 5-77 years). The follow-up time for 630 patients ranged from 1 month to 20.8 years (mean 13.0 years). The overall adjusted survival rate was 86.7% at 5 years and 64.2% at 10 years. In a univariate analysis the stage of disease at diagnosis, age, sex, and type of disease (sporadic, familial) were relevant prognostic factors, with a better prognosis for young female patients with familial disease and diagnosed at an early stage. In a multivariate proportional hazards analysis, the difference in the survival rate of patients with familial disease versus those with the sporadic form disappeared, while prognostic information provided by age and sex was still significant. The poorer prognosis of patients with sporadic medullary thyroid carcinoma may be related to the patients' older age at detection and more advanced tumor stage at diagnosis. There seems to be no difference in biological behavior between tumors of the sporadic and those of the familial type.

Adolescent↗

Postprandial release of glucagon-like peptide-1, pancreatic glucagon, and insulin after esophageal resection.

Postprandial concentrations of glucose and the immunoreactivity of insulin, glucagon-like peptide-1 (GLP-1), and pancreatic glucagon were measured in 10 patients who had undergone esophageal resection (ER) and replacement by the stomach. Emptying of the esophageal substitute was assessed by scintigraphy using a 99Tc-labeled solid test meal. The data were compared with measurements performed in 14 controls, in 7 of whom gastric emptying was measured. The gastric emptying half time was 6.8 +/- 6.2 min (median 144 s) in ER cases, significantly shorter than in controls: 70 +/- 29 min (median 51 min). The early integrated (first 30 min) and total integrated insulin and GLP-1 concentrations were significantly higher than in controls. In 3 of 10 esophagectomy patients the blood glucose concentration fell below 3.8 mmol/l postprandially. High GLP-1 concentrations in the first 30 min were associated with low serum glucose during the 2nd h postprandially when all the hypoglycemic episodes occurred. It is concluded that rapid emptying of the esophageal substitute induces the exaggerated GLP-1 response, which is a main factor for reactive hypoglycemia.

Blood Glucose↗

Limitations of clearance determination using the single sample distribution volume method. An error analysis on the basis of compartment models.

To investigate the error possibly contained in the single sample distribution volume method for the determination of renal clearance, a mathematical model was applied to describe the effect of changes in distribution volume, clearance, intravascular space, intracompartmental exchange and the time point of blood sampling. The method was found to be valid only under well-defined circumstances (Topt = 45 +/- 5 min, Cl = 390 +/- 50 ml/min, Vd = 16.7 +/- 4 l, alpha = 0.05.V1 ml/min, V1/Vd = 0.5 +/- 0.05) as shown in sample calculations. Two-compartment model-based error calculations demonstrate that this technique implies at best an uncertainty of +/- 10% or more. Whilst it can be used preferably in healthy, normal-weight adults, it is not applicable, without error, under all other circumstances.

Humans↗

Frequency and significance of cervicomediastinal lymph node metastases in medullary thyroid carcinoma: results of a compartment-oriented microdissection method.

The frequency and significance of cervicomediastinal lymph node metastases have been investigated in 82 medullary thyroid carcinoma (MTC) patients retrospectively comparing two surgical techniques of lymph node dissection: selective lymphadenectomy (n = 63) versus compartment-oriented microdissection (n = 35). No positive correlation was observed between primary tumor size and the number of lymph node metastases. In patients with lymph node metastases proven histologically, 42% showed only cervical involvement (35% unilateral--type A, 7% bilateral--type B) and 22% cervicomediastinal lymph node involvement (15% cervico-unilateral and mediastinal--type C, 7% cervicobilateral and mediastinal--type D). Biochemical cure was 83% in node-negative patients but only 21% in node-positive patients. In node-positive MTC, calcitonin normalization was achieved in none with bilateral lymph node involvement but only in those unilateral lymph node metastases (31% in type A, 17% in type C). Survival and biochemical cure are significantly improved by application of the compartment-oriented microdissection method more so at primary surgery than at reoperation.

Carcinoma↗

[Unilateral renal artery stenosis. Color-coded Doppler sonography and captopril scintigraphy in a 13-year-old patient].

Modern noninvasive techniques, such as doppler sonography or color-encoded doppler sonography, have only rarely been used for diagnosis of renovascular hypertension in children. In the following case report, we describe the successful diagnosis of renovascular hypertension in a 13-year-old girl by using color-encoded doppler sonography and Captopril renal scintigraphy. The patient was admitted with hypertension of 180/130 mmHg. Laboratory findings showed elevated plasma renin and aldosterone concentrations. No abnormalities were found by abdominal sonography, isotope renography, intravenous pyelography, or in venous digital subtraction angiography. However, subsequent color-encoded doppler sonography clearly showed evidence of an artery stenosis of the right kidney. Furthermore, isotope renography one hour after oral administration of captopril revealed an almost complete loss of glomerular filtration rate of the right kidney. Based on these findings, arterial digital subtraction angiography, including transluminal angioplasty, was performed. During this treatment procedure, the right renal artery stenosis could be confirmed and was subsequently dilated without complication. In the following twelve months the patient remained normotensive and required no further antihypertensive drug treatment.

Angiography, Digital Subtraction↗

[Mucociliary clearance in childhood].

AIM OF THE STUDY: A new, nearly monodisperse human serum albumin particle produced by air-pressure-nebulization was inhaled by children and lung-transplant patients. METHOD: After inhalation of the particles obtained with an air-pressure nebulizer, the initial deposition pattern showed a marked tracheobronchial deposition which could be reproducibly obtained without a special breathing technique, the alveolar deposition being not higher than 10%. With the use of 99mTc, the radiation exposure is limited to a level which is low enough for children, but images can be taken up to 24 hrs later. Further parameters for in vivo characterization of the mucociliary function are the 24 h retention pattern and the velocity of particle motion in the trachea. RESULTS: Within the first 45 minutes, the global clearance rate was 51% in healthy children, which is rather high in comparison with the literature, most likely due to size of particles and the selection of patients with a mean age of 10.7 years. In ciliary dysfunction, the initial clearance rate was 16% and 46% within 24 h. CONCLUSIONS: With simplification of the preparation, application, and examination technique, this method is to be used in children, so that a wider use can be anticipated. The normally fast initial elimination of particles allows quick differentiation of normal and impaired ciliary function.

Adolescent↗