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Biomedical subjects

M Grussendorf

Publications and source records attributed to M Grussendorf.

At least 37 records · Page 2Linked to original sources

[Dyskinesia of the abdominal musculature in hypochondria].

A 73-year-old woman with a history of chronic hypochondria, depression and abdominal symptoms, such as colics, flatulence and changing fecal consistency, was diagnosed as having an "irritable colon" syndrome and "hypochondria". Over a period of ten years she had been taking regularly various psychoactive drugs, especially diazepins and amitryptiline. Three years ago she began to have wave-like movements of the abdominal wall, interpreted as intestinal hyperperistalsis with chronic subileus. Radiological and endoscopic examinations were normal, but wave-like contractions of the abdominal musculature were demonstrated on electromyography. The most likely cause is the chronic abuse of psychoactive drugs over many years. In case of abdominal symptoms attention should be paid to the abdominal wall, not only the gastrointestinal tract.

Abdominal Muscles↗

Nerve growth factor (NGF) sensitizes human medullary thyroid carcinoma (hMTC) cells for cytostatic therapy in vitro.

Medullary thyroid carcinoma (hMTC) cells were established from nine patients with MTC disease to initiate a new approach of adjuvant medical therapy in these patients. We measured calcitonin (CT) secretion, DNA synthesis, and cell proliferation in vitro and their response to various substances. Nerve growth factor (NGF) (0.01 to 10 micrograms/ml), glucagon (0.01 to 100 micrograms/ml), and isoproterenol (4 to 500 micrograms/ml) stimulated CT secretion and DNA synthesis in hMTC cells. Other substances, calcium (1.0 to 15 mmol), pentagastrin (1.0 to 50 mumol), dibutyryl-cyclic-adenosine-monophosphate (1.0 to 100 mumol), and phorbol ester TPA (1.0 to 100 nmol), stimulated CT secretion but not DNA synthesis. In addition, NGF enhanced cell proliferation of hMTC cells 2- to 3- fold and caused an increased sensitivity of these cells for chemotherapy in vitro. Thus 0.5 microgram/ml doxorubicin (half-maximal effective dose) induced a cell death rate of up to 32.8%, which was enhanced by preincubation with NGF to 68.1% (1.0 microgram/ml, NGF) and to 100% (10.0 micrograms/ml, NGF), respectively. Pulsative stimulation of APUD cell carcinomas with NGF may therefore improve the response rate of these tumors to chemotherapy, which would be of significant clinical importance for patients with residual postoperative MTC tissue.

Antineoplastic Agents↗

Vaccination against hepatitis B in patients with renal insufficiency.

To define the degree of renal insufficiency at which the immune response to vaccination against hepatitis B is impaired, anti-HB concentrations after vaccination with 20 micrograms HB-Vax at 0, 1 and 6 months were examined in 76 dialysis patients, 24 patients with incipient renal failure (S-creatinine 1.4-3.5mg/dl) and in 43 controls. Compared with controls, seroconversion rate and anti-HB concentrations were significantly (p less than 0.02) lower in patients with incipient renal failure. The time course of anti-HBs in dialysis patients with successful vaccination, either with three doses (0, 1, 6 months) or with five doses (0, 1, 2, 4, 6 months) of HB-Vax was compared with healthy controls. The proportion of patients losing anti-HBs and the decrease of antibody concentration was significantly greater in dialysis patients immunised with three doses of the vaccine. In dialysis patients vaccinated with five doses, the percentage losing HB antibodies was slightly higher than in controls, but final titres after 24 months were comparable.

Adult↗

[Systemic light-chain disease as a complication of plasmacytoma].

An asymptomatic multiple myeloma of the kappa-light chain type was found in a patient with nephrotic syndrome and renal insufficiency. Light microscopy showed nodular glomerulosclerosis of the kidney similar to diabetic glomerulosclerosis. Diabetes mellitus could not be demonstrated. kappa-Light chain deposits could be shown by immunohistology in the mesangium and the glomerular and tubular basal membrane. In addition, massive kappa-light chain deposits in the sinusoidal walls of the liver and at the dermoepidermal junction of the skin and in the corium were found.

Antineoplastic Combined Chemotherapy Protocols↗

A comparison of the effectiveness of 131I whole body scans and plasma Tg determinations in the diagnosis of metastatic differentiated carcinoma of the thyroid: a retrospective study.

In 68 patients with proved metastases of differentiated thyroid carcinoma the comparative value of the 131I whole body scan and plasma Tg measurements in establishing the diagnosis of metastasis or recurrence was analyzed retrospectively. At the time of primary therapy most metastases were diagnosed by the post-therapy scan (78%). Eight of 9 scintigraphic negative metastases in the post-therapy scan were indicated by elevated Tg levels (greater than 10 ng/ml). Twenty-four of 28 recurrences after a disease free interval were negative in the 2 mCi 131I scan, 18 of these patients were Tg positive. Of the 4 recurrences with positive 131I uptake all were Tg positive; two of them only during endogenous TSH stimulation. It is concluded that the routine 2 mCi whole body scan is less efficient in follow-up than is generally assumed. The most important follow-up parameter for these patients is the plasma Tg which can be obtained under suppressive therapy if a sensitive assay is used. In patients with a negative post-therapy scan and a negative Tg (less than 5 ng/ml) it seems justified to omit further 131I whole body control scans as long as Tg remains negative.

Carcinoma↗

[The value of serum thyroglobulin determination in the after-care of patients with differentiated thyroid neoplasms].

Plasma thyroglobulin (Tg) was determined by radioimmunoassay in 219 patients with differentiated carcinoma of the thyroid gland after treatment by total thyreoidectomy and at least 2 131I therapies with a total of 170 mC. Of 145 patients without residual thyroid tissue and a negative whole body scan, 6 patients exhibited significant Tg levels. It remains unclear whether these individuals will develop recurrency later on. Of 23 patients with proven metastases, 14 had extremely high Tg concentrations of greater than 1000 ng/ml. In 6 cases Tg was between 20 and 280 ng/ml and in 3 individuals Tg levels below 10 ng/ml were measured. The reason for low Tg concentrations in some patients with proven metastases is unknown. At present plasma Tg measurements therefore cannot be recommended as substitution for whole body scanning. However, plasma Tg is an important additional parameter in the follow-up of patients with differentiated carcinoma of the thyroid.

Adenocarcinoma↗

[Thyreotrophic hypophysial function after surgery for euthyroid goiter or autonomous adenoma].

44 euthyroid patients with nodular goiter and 23 patients with autonomous adenomas were treated by hemithyrectomy or subtotal thyrectomy. Thyroid function was followed over 6 weeks post-operation by TRH tests, which were performed before and at the 5th, 14th, 28th and 42nd day after operation. Bilateral subtotal thyrectomized patients with euthyroid goiter showed a continous increase of basal and TRH stimulated TSH level into the hypothyroid range. 19 of 25 patients were hypothyroid 6 weeks after operation. In contrast, 14 of 19 hemithyrectomized patients with euthyroid goiters remained euthyroid during the time investigated; 5 patients showed a transient TSH increase into the hypothyroid range but were euthyroid again after 6 weeks. TSH levels obtained from patients operated for autonomous adenoma may not yet reflect thyroid function during the time interval investigated here. We conclude that all patients with euthyroid goiter after bilateral subtotal thyrectomy should receive hormone substitution because they are at high risk to develop recurrency. However, we propose that in patients hemithyrectomized for euthyroid goiters the decision of long term hormone substitution should be cased on the result of a TRH-test 3--4 month after operation. Substitution with thyroid hormone should be preferred to iodide because it is unclear yet how far a failure in iodide organification and hormone synthesis is the reason for goiter recurrency.

Adenoma↗

Studies on the deiodination of 3,3',5'-T3 (reverse T3) to 3,3'-T2 (diiodothyronine) in rat liver.

Properties of the deiodination reaction of rT3 to 3,3' T2 in rat liver homogenate are reported and compared with T4 to T3 conversion under similar conditions. pH optimum and SH-group dependency of these two reactions are quite different, though both are concerned with 5' deiodination. The most potent activator of the reaction rT3 to T2' is dithiothreitol; the enzyme activity increases almost linearly even at very high concentration of this compound (the same is true for mercaptoethanol). Glutathione and coenzyme A, show only small activating effects. T4 to T3 and rT3 to T2' converting is being induced almost parallel in thyrectomized rats substituted with T4 or T3.

Animals↗

Radioimmunoassay for 3,3'-diiodothyronine in human serum.

A specific radioimmunoassay for measurement of 3,3'-diiodothyronine (T2') is presented. With the method described (ethanol extraction of native serum and lyophilisation of the extract) the application of 400 microliter serum equivalent in the assay is possible. Standards and sera are treated similarly. The detection limit is 0.625 ng/dl, comparison between direct assay and dried extract assay shows good correlation. Mean normal T2' serum concentration in man is 7.2 ng/dl (range 3 to 11 ng/dl), hypothyroid: below 3.0 ng/dl, hyperthyroid: 11-64 ng/dl (range). T2' level in cord-blood of newborns: 16.5 ng/dl. The urinary excretion of free T2' of normal man is 0.49 microgram/24 h (mean), a relatively high excretion rate in comparison to the low serum level.

Adult↗

Investigations on the deiodination of thyroxine (T4) to 3,3'-diiodothyronine (3,3'-T2) in rat liver homogenate.

Properties of an inactivating pathway of T4 to 3,3'-diiodothyronine (T2') in rat liver homogenate are described. The intermediate product (of this reaction sequence) is reverse T3 (rT3) which is very labile and cannot be measured at pH 7.5. The apparent KM of the reaction rT3 to T2' is 2 X 10(-8) M. The activities catalyzing the reactions T4 to T3, T4 to T2' and rT3 to T2' are found in the 100 000 X g pellet. Propylthiouracil inhibits all three activities to a similar degree; alpha-methyl-p-tyrosine has no effect. T3 seems to be only a minor source of T2' production. The molar ratio of the two T4 deiodination pathways T4 to T3/T4 to T2' under these conditions is about 1.7; however, by changing the pH this ratio could be significantly altered.

Animals↗

Correlation of reverse-T3 and 3,3'-T2 (T2') plasma concentrations under physiological and experimental conditions in man.

T2' plasma levels are measured under different conditions and correlated to the repective rT3 concentrations. Specific RIAs for T2' and rT3 are used. Pharmacological doses of T3 cause an increase of plasma T2'; if T3 or T4 doses are administered to an athyroid patient which cause a similar level of plasma T3 the increase of T2' is much larger during T4 treatment. Cord blood levels of T2' are 2--3-fold higher than in normal adults whereas rT3 concentrations are about 10 times higher than normal. After birth rT3 and T2' levels decrease in about a parallel manner. After a bolus iv injection of 500 microgram rT3, T2' starts to increase as early as 2 min after injection. PTU in therapeutic doses causes a rapid increase of plasma rT3 with a maximum 4 h after ingestion. A dose of 150 mg PTU causes a maximum of about 100% above baseline. T2' also increases but to a lesser degree (about 50% above baseline). We conclude that rT3 is a most important precursor of T2' whereas T3 contributes only to a minor degree to the total T2' production under physiological conditions.

Adult↗

[Plasma levels of 3,3', 5'-T3 (reverse-T3) under various functional thyroid conditions].

Reverse T3 (r-T3) was measured in unextracted human plasma under different clinical conditions. The mean normal concentration was 0.20 ng/ml. In thyreotoxic patients r-T3 was elevated in the majority of the cases, however, it was normal in three cases of T3-toxicoses. Thyrectomized patients during different hormon substitution showed r-T3 levels corresponding to the T4 concentrations measured. Patients with severe chronic illnesses and low T3 showed normal to considerably elevated r-T3 levels. According to these results r-T3 is not of additional value in the diagnosis of thyroid disorders.

Hyperthyroidism↗

[Approach to a differentiated recurrence prevention following struma surgery].

Changes of the pituitary-thyroid axis were studied in 70 patients (45 with euthyroid goiters, 25 with autonomous adenomas) preoperatively; over a 6-week postoperative interval without thyroid-hormone treatment; under T4 therapy increased stepwise and maintained for 1 year; and over a period of 12 weeks after its withdrawal. The postoperative thyrotropic function obviously depends on the preoperative condition and thereby on the quality of the remaining tissue as well as on the extent of the operation and thus the amount of remaining tissue. The frequency of a "prehypothyroid" status in the early postoperative course is high (77%) after bilateral resection for euthyroid goiter, but decreased 1 year after the operation (47%). After unilateral resection for euthyroid goiters and after bilateral and unilateral resection or enucleation for autonomous adenomas, the remaining tissue is for the most part sufficient to avoid increased pituitary stimulation. Prophylaxis of recurrent goiter with thyroid hormones could be prescribed individually on the basis of the postoperative function of the pituitary-thyroid axis.

Adenoma↗

Induction of the thyroxine (T4) to triiodothyronine (T3) converting enzyme in rat liver by thyroid hormones and analogs.

In thyroidectomized, unsubstituted rats the T4 to T3 converting activity of liver homogenate is reduced to about 30% of that in unoperated control animals. The enzyme activity can be reinduced dose-dependently with T4. To achieve a normal activity, high, non-physiological plasma T4 concentrations are needed. Plasma T3 levels are much better correlated to the T4 to T3 converting activity. Pure T3 proved to be a more potent enzyme inducer than T4. No difference could be detected between L- and D-T3. Tyrosine, diiodotyrosine, 3,3'-diiodothyronine and 3,3',5'-T3 (reverse-T3) showed no inductive effect for the enzyme. These results demonstrate that the T4 to T3 converting enzyme is specific and shows regulatory properties.

Animals↗

Properties of the thyroxine (T4) monodeiodinating system in rat liver homogenate.

The monodeiodination of T4 in rat liver homogenate was studied. The two possible products of this reaction show very different properties. The metabolically very active T3 is rather stable in this system whereas the biological inactive reverse T3 (rT3) disappears very rapidly. This explains the low apparent rT3 production in the incubation mixture even under optimal conditions and the peculiar pH profile. The T4 to T3 converting reaction can be increased by the addition of mercaptoethanol to the medium; no further activation is possible by several cofactors tested. The apparent KM of the reaction is 1.6 x 10(-6) M. Reverse T3 does inhibit the reaction non competitive; Ki = 2 x 10 (10-8) M. Alpha-methyl-para-tyrosine, a specific inhibitor of tyrosine hydroxylase, has no significant effect on the reaction.

Animals↗

3,3',5'-Triiodothyronine (Reverse T3) in amniotic fluid and cord serum.

3,3',5'-triiodothyronine (reverse T3, rT3) was measured in 122 samples of amniotic fluid obtained between the 29th--40th weeks of gestation, and in the blood of 37 newborn and their mothers. The mean rT3 concentration in amniotic fluid was 0.769 +/- 0.47 ng/ml, with a slight decrease from the 29th--40th weeks of gestation which was not statistically significant. Because of the great scatter of rT3 concentrations in amniotic fluid, its estimation does not seem to be useful in prenatal diagnosis of hypothyroidism. The mean rT3 concentration in cord blood (2.62 ng/ml; range 1.4--4.9 ng/ml) was greatly elevated in comparison to the mean maternal level at delivery (0.34 ng/ml; range 0.08--0.69 ng/ml). The possible use of rT3 measurements in cord blood as a screening test for congenital hypothyroidism is discussed.

Amniotic Fluid↗

[Hormone concentrations in thyroid gland tissue and plasma in autonomous thyroid adenomas with and without thyrostatic pretreatment].

The thyroid hormone concentrations of T2, T3 (and the inactive R-T3) were determined in thyroid tissue of 20 patients with autonomous adenomas. High concentrations were found in scintigrafically decompensated adenomas without preoperative thyrostatic treatment. Decompensated adenomas after thyrostatic treatment, compersated adenomas and a group of 9 euthyroid goiters showed no difference in tissue-concentrations of T4 and T3. The amount of tissue-R-T3 seems to be lowered in autonomy. The plasma-concentration of T3, which was intraoperatively elevated in the venous effluent from decompensated adenomas without thyrostatic treatment, was significantly lower in the blood draining decompensated adenomas after thyrostatic treatment as well as compensated adenomas.

Adenoma↗