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Biomedical subjects

P Groth

Publications and source records attributed to P Groth.

At least 19 recordsLinked to original sources

Lithium as an adjunct to radioiodine therapy in Graves' disease for prolonging the intrathyroidal effective half-life of radioiodine. Useful or not?

AIM: Evaluation of intrathyroidal kinetics of radioiodine with and without lithium as adjunct with respect to the increase in radiation dose delivered to the thyroid. PATIENTS, METHODS: 267 patients in three groups were included in the study. Group I with 227 patients served as control group, Group II with 21 patients and Group III with 19 patients were distinguished by an intrathyroidal half-life of radioiodine below 3.5 days in the diagnostic test. Patients in Group III received 885 mg lithium carbonate a day for 2 weeks as adjunct to radioiodine therapy. Both diagnostic and therapeutic radioiodine kinetics were followed up by at least 10 uptake measurements within a minimum of 48 h. Kinetics of radioiodine were defined mathematically as balance of the thyroidal iodine intake and excretion by a two-compartment model. RESULTS: Under therapy the maximum uptake of radioiodine was reduced by nearly 10% in all groups, in Group I, the effective half-life as well as the product of maximum uptake x effective half-life as an equivalent of radiation dose independent of thyroid volume was lowered in the same magnitude. In Group II, the energy-dose equivalent remained constant under therapy. With adjunct lithium in Group III, the effective half-life was prolonged significantly by factor 1.61 +/- 0.49 and the volume-independent energy-dose equivalent by factor 1.39 +/- 0.37. No severe side effects of lithium were observed. CONCLUSION: Using lithium as adjunct to radioiodine therapy increases the radiation dose delivered to the thyroid by 39% on average and nearly 30% of radioiodine activity can be saved in these patients. Lithium is recommended in patients with very short effective half-life in the diagnostic test in order to reduce the activity required and whole-body radiation dose.

Adolescent↗

[Results of a risk adapted and functional radioiodine therapy in Graves' disease].

UNLABELLED: Aim of this study was to find out, if results of a functional orientated radioiodine therapy in Graves' disease could be optimized using a risk adopted dose concept. PATIENTS, METHOD: 351 patients with Graves' disease were treated for the first time between 11/97 and 8/01. The basic dose was 125 Gy, which was increased up to 250 Gy in a cumulative manner depending on clinical parameters (initial thyroid metabolism, thyroid volume, immunoreactivity). Two different methods of dosimetry were used. Occasional thyreostasis was withdrawn two days before the radioiodine test was started. Follow up was done on average 8 +/- 2.4 (4-17.2) months. TSH > or = 0.27 microIU/mL confirmed as a measure of the success. RESULTS: With improved pretherapeutic dosimetry and a mean target dose of 178 +/- 31 Gy (n=72) therapeutic success occurred in 66.7%, in 51.4% euthyreosis was restalled and in 15.3% of patients hypothyroidism was seen (TSH > 4.20 microIU/mL). With simplified pretherapeutic dosimetry and a mean target dose of 172 +/- 29 Gy (n=279) results were moderately impaired (63.8%, 40.1% and 23.7%). With increasing target dose therapeutic failure increased, as insufficiently adopted risk factors for therapeutic failure turned out the initial thyroid metabolism, the TcTU(s) as the (h)TRAb titer. CONCLUSION: Functional orientated RIT can be optimized by including illness specific characteristics, principal limitations are a high initial thyroid metabolism, a large thyroid volume and a high (h)TRAb-titer.

Graves Disease↗

Clinical impact of retinoids in redifferentiation therapy of advanced thyroid cancer: final results of a pilot study.

Differentiated thyroid cancer is a malignant tumour that has a fairly good prognosis, with patients surviving for many years. Multimodal therapy with surgery, radioiodine therapy and TSH suppressive medication is of proven efficacy. However, loss of differentiation is observed in up to one-third of patients with differentiated thyroid cancer, paralleled by an increase in tumour grading and loss of thyroid-specific functions (thyrotropin receptor, iodine accumulation). Such tumours may no longer be amenable to standard treatment protocols, including TSH suppression and radioiodide therapy. Retinoic acids have been shown to exert re-differentiating effects on thyrocytes in various experimental studies and case reports, and it was on this basis that this pilot study was initiated. Patients with advanced thyroid cancer and without the therapeutic options of operation or radioiodide therapy were treated with 13- cis-retinoic acid at a dosage of 1.5 mg/kg body weight daily over 5 weeks. Parameters for assessment of the therapeutic effect were serum thyroglobulin (TG) levels, radioiodine uptake, and tumour size prior to and after retinoid treatment. Fifty patients were evaluated for response, classified as reduction in tumour size and TG levels, stable disease or disease progression. Thirteen patients showed a clear increase in radioiodine uptake, and eight a mild increase. TG levels were unchanged or decreased in 20 patients. Tumour size was assessable in 37 patients; tumour regression was observed in six, and there was no change in 22. In total, a response was seen in 19 patients (38%). Response to retinoid therapy did not always correlate with increased radioiodine uptake, so other direct antiproliferative effects have to be assumed. The encouraging results of the study and the low rate of side-effects with good tolerability of retinoids warrant further studies with altered inclusion criteria and employment of other redifferentiating drugs or combinations of agents.

Adenocarcinoma↗

[Results of TcTUs-optimized radioiodine therapy in multifocal and disseminated autonomy].

AIM: The presented study prospectively evaluates the efficacy of optimized radioiodine therapy in patients (pts) with multifocal (MFA) and disseminated (DISA) autonomy. The target dose was related to the total thyroid volume and was increased in moderate and nonlinear increments from 150 to 300 Gy dependent on the pretherapeutic Tc-99m pertechnetate thyroid uptake under suppression (TcTUs). Patients with focal autonomy were treated with a target dose independent of TcTUs and were used as control group. METHODS: The data of 641 pts (518 women, 123 men) were evaluated, 466 pts with MFA or DISA and 175 pts with focal autonomy. In pts with MFA and DISA the target dose was increased in four steps: TcTUs < 3%: 150 Gy, > 3-6%: 200 Gy, > 6-12%: 250 Gy and > 12%: 300 Gy. In pts with focal autonomy a fixed target dose of 300 or 400 Gy was applied. The radioactivity to be administered was calculated using a modified Marinelli formula. The follow-up examination was performed at the earliest after four, on average after eight months. Normalization of TSH was the only criterion for successful therapy. RESULTS: The success rate in pts with latent or manifest hyperthyroidism in focal autonomy was 91.5%, therapy was not successful in 5.1% and hypothyroidism occurred in 3.4%. The average success rate in pts with MFA and DISA was 91.5%, therapy failed in 7.5% and a very low rate of 1% with hypothyroidism was seen. CONCLUSION: The presented optimized therapy concept with calculated, nonlinear increase of the target dose according to the TcTUs-level guaranteed even in MFA and DISA a high success rate comparable to that in focal autonomy along with a very low rate of hypothyroidism.

Female↗

A new hot spot for mutations in the ret protooncogene causing familial medullary thyroid carcinoma and multiple endocrine neoplasia type 2A.

One hundred and eighty-one families with multiple endocrine neoplasia type 2A (MEN-2A) or familial medullary thyroid carcinoma (FMTC) have been investigated for mutations in the ret protooncogene in Germany. In 8 families with FMTC or MEN-2A, no mutation could be detected in the cysteine-rich domain encoded in exons 10 and 11 of the ret protooncogene. DNA sequencing of additional exons (no. 13-15) revealed rare noncysteine mutations in 3 families (codons 631, 768, and 844). In contrast to these rare events, heterozygous missense mutations in exon 13, codons 790 and 791, were found in 5 families (4 with MTC only; 1 family with MTC and pheochromocytoma) and 11 patients with apparently sporadic tumors. Two different mutations in codon 790 (TTG-->TTT, TTG-->TTC; Leu790Phe) and one mutation in codon 791 (TAT-->TTT; Tyr791Phe) created a phenylalanine residue. We conclude that codons 790 and 791 of the ret protooncogene represent a new hot spot for FMTC/MEN-2A causing mutations. With the discovery of these considerably common mutations in codons 790 and 791 and the identification of some rare mutations, 100% of the German FMTC/MEN-2A families could be characterized by a mutation in the ret protooncogene.

Adult↗

[Paradoxical effect of radioiodine therapy in functional thyroid autonomy and mild immunothyropathy].

AIM: To examine all cases with Graves' disease after radioiodine therapy of autonomously functioning thyroid tissue (AFFT) in order to find the cause. METHODS: We retrospectively studied 1428 pts who were treated between 11/93 and 3/97 with radioiodine for AFTT and who underwent at least one control examination. RESULTS: 15 (1.1%) of all pts developed Graves' disease 8.4 (4-13) months after radioiodine therapy. There was no direct suggestion of Graves' disease (TRAK negative, no endocrine ophthalmopathy) in any pt at the time of radioiodine therapy. More detailed analysis of anamnestic data, however, revealed evidence that immunothyropathy predated radioiodine therapy in 11 of the 15 pts. Paradoxical effects of radioiodine therapy manifested as an increase in immunothyropathy in 14 pts, a deterioration in metabolism in 11 pts and a first occurrence of endocrine ophthalmopathy in 5 pts. CONCLUSION: Exacerbation of preexisting, functional primarily insignificant immunothyropathia is held responsible in most cases for the observed paradoxical effects after radioiodine therapy, resulting in radiation-induced manifest Graves' disease; however no therapeutical consequences are recommended.

Aged↗

Anticholinergic agents. 2. Absolute configurations of 2-methyl-1,1-diphenyl-3-(1-piperidyl)-1-propanol and 2-methyl-1,1-diphenyl-3-(1-pyrrolidyl)-1-propanol. Crystal structures of the corresponding mandelates.

Racemic 2-methyl-1,1-diphenyl-3-(1-piperidyl)-1-propanol (4) and 2-methyl-1,1-diphenyl-3-(1-pyrrolidyl)-1-propanol (5) have been synthesized and optically resolved employing (R)- and (S)-mandelic acid, respectively, as resolving agents. The absolute configurations of the enantiomers of 4 and 5 have been established as (-)-(R) and (+)-(S) by crystal structure analyses of (-)-(R)-2-methyl-1,1-diphenyl-3-(1-piperidinio)-1-propanol (+)-(S)-mandelate and (+)-(S)-2-methyl-1,1-diphenyl-3-(1-pyrrolidinio)-1-propanol (-)-(R)-mandelate. The corresponding methiodides have been prepared.

Crystallography↗

Syntheses of (S)-(+)-trihexyphenidyl hydrochloride and (S)-(+)-procyclidine hydrochloride, two anticholinergics, using (S)-(-)-3-cyclohexyl-3-hydroxy-3-phenylpropanoic acid as chiral synthon.

The absolute configuration of the more active (-)-enantiomer of the anticholinergic trihexyphenidyl hydrochloride has been established as (R) by syntheses of (S)-(+)-procyclidine hydrochloride, whose absolute configuration has been established previously, and (S)-(+)-trihexyphenidyl hydrochloride from the same chiral building block, viz. (S)-(-)-cyclohexyl-3-hydroxy-3-phenylpropanoic acid. Both enantiomers of this chiral synthon were prepared by optical resolution of the corresponding racemate, employing (R)- and (S)-1-phenylethylamine, respectively, as resolving agents.

Circular Dichroism↗

Effect of atropine on the eustachian tube function.

The effect of atropine on the eustachian tube function was studied by means of a recently designed method. The results out of 20 examined ears showed that atropine significantly reduced both active and passive functions of the eustachian tube. The findings are discussed and it is concluded that the method used might be a valuable tool in forthcoming studies of pharmacological effects on the eustachian tube function.

Air Pressure↗

Pressure chamber tests for selection of aircrew.

The Eustachian tube function requested from flying personnel today is generally regarded as acceptable if hearing and otoscopic findings are normal and there is no history of ear disease. Since increasing performance of modern aircrafts place more rigorous demands on the equilibrating capacity of the Eustachian tube and difficulty to clear the ears already is the most common cause of temporary grounding among flying personnel, the present requirements for tubal function might gradually get more and more inefficient. Inability to equilibrate in flight may lead to temporarily reduced hearing, acute ear pain and alternobaric vertigo that will affect the pilot's capacity and thus constitute a problem of flight safety. A testing procedure that makes it possible to continuously measure the middle ear pressure in subjects with intact eardrums during simulated flights in a pressure chamber would introduce a possibility to find basic medical standards of Eustachian tube function to be used in the selection of flying personnel. Student pilots, accepted for primary flight training, were examined in the present study by such a method. A comparison is made with the results of other tests of the Eustachian tube function in order to find out the relevance of the latter tests in the selection of flying personnel. The results are presented and discussed.

Adolescent↗

[Surgical aspects of the treatment of malignant thyroid gland tumors].

95 cases with primary malignant thyroid tumours underwent surgery from 1965 to 1977. In view of the interdisciplinary character of treatment and independent of histological differentiation, total thyroidectomy should be performed. Differentiated carcinomas should be treated by selective dissection of suspected cervical lymph nodes. Surgical intervention of undifferentiated and medullary carcinomas should be followed by unilateral or bilateral neck-dissection. The survival rate is shown to depend on histological stage and extension of the tumour.

Adenocarcinoma↗

Reliability in tests of the eustachian tube function.

With the aid of a quantitative impedance method and a pressure chamber, the capacity of the Eustachian tube to equilibrate pressure differences across the tympanic membrane was repeatedly determined in 20 otologically healthy men. The test-retest reliability was calculated from five determinations of static pressure equilibration of over- and underpressures of 10 cmH2O and 10 determinations of equilibration of dynamic pressure changes. The pressure opening level of the tube during pressure increase in the middle ear was significantly lowered in the initial determinations. The residual pressure in the middle ear after maximum equilibrating efforts during pressure increase in the chamber was also significantly lowered. For the rest, the test-retest reliability was good. Ears with perfect tubal function had better test-retest reliability for all parameters tested than ears with poorer function. The significance of repeated measurements and the value of reliability determinations are discussed.

Acoustic Impedance Tests↗

Effect of flight on the Eustachian tube function and the tympanic membrane system--a follow-up study.

The Eustachian tube function in 32 aviation trainees was comprehensively tested in simulated flights in a pressure chamber on three occasions during their training. Their mean flight experience between tests comprised 150 h in jet training planes and 260 h in jet fighters. Their capacity to clear the ears in descent did not improve convincingly between tests, but the pressure opening level in ascent was significantly lowered. The elasticity of the eardrum system was significantly increased. The results suggest that the first test, before the flight training, is reliable for selection purposes. Reasons for difficulties in finding good agreement between test results and results of actual flight training are discussed.

Aerospace Medicine↗