Focus on radioiodine-131 biokinetics: the influence of methylprednisolone on intratherapeutic effective half-life of 131I during radioiodine therapy of Graves' disease.

AIM: Radioiodine therapy (RIT) may trigger the development of Graves' ophthalmopathy (GO) or exacerbate pre-existing subclinical GO. Therefore, glucocorticoid administration is recommended for patients with pre-existing GO. Aim of this study was to analyze the influence of glucocorticoid therapy with methylprednisolone on intratherapeutic effective half-life (EHL) of radioiodine-131 in patients with Graves' disease (GD) as recent studies showed an effect for prednisolone. METHODS: In a retrospective study, 264 patients with GD who underwent RIT without any additional antithyroid medication were evaluated. Intrathyroidal EHL was determined pre- and intratherapeutically. Patients with co-existing GO (n = 43) received methylprednisolone according to a fixed scheme starting 1 day prior to RIT, patients without GO (n = 221) did not receive any protective glucocorticoid medication. The ratios of EHL during RIT and during radioiodine uptake test (RIUT) were compared. RESULTS: Patients receiving methylprednisolone showed a slight decrease of the mean EHL from 5.63 d (RIUT) to 5.39 d (RIT) (p > 0.05). A comparable result was obtained in patients without glucocorticoids (5.71 d (RIUT) to 5.47 d (RIT); p > 0.05). The ratios of the EHL between RIT and RIUT failed to show a significant difference between the two groups. EHL is therefore not significantly influenced by an additional protective treatment with methylprednisolone. CONCLUSIONS: In the present study a decreased intrathyroidal EHL under glucocorticoid medication with methylprednisolone could not be detected. Therefore, co-medication with methylprednisolone in patients with GO may be preferred to avoid an intratherapeutic decrease of EHL by accompanying protective glucocorticoides.

Design and optimization of 20-O-linked camptothecin glycoconjugates as anticancer agents.

To improve the biological profile of 20(S)-camptothecin, a novel class of 20-O-linked camptothecin glycoconjugates has been designed for preferential cellular uptake into tumor cells by an active transport mechanism. Such conjugates have been optimized for enhanced solubility, stabilization of the camptothecin lactone ring, sufficient hydrolytic and proteolytic stability, and for an overall improvement in tumor selectivity. The constitution of the peptide spacer has a major impact on stability and biological activity of the conjugates both in vitro and in vivo. Glycoconjugates 17-22 with valine residues at the linkage position to camptothecin are sufficiently stable and show good antitumor activity in vitro against HT29 and other tumor cell lines. Fluorescence microscopy and flow cytometry experiments indicate that glycoconjugates such as 19 are taken up into lysosomal compartments of the tumor cell line HT29 by an active transport mechanism. The steric configuration of the particular amino acid residues linked to the camptothecin moiety has a major impact on the in vivo activity of the corresponding glycoconjugates in the breast cancer xenograft MX-1 model. Inhibiting tumor growth by >96%, the glycoconjugates 19 and 21 show the best activity in this particular model and have been investigated more extensively. The glycoconjugate 19 compares favorably to topotecan 4 and glycoconjugate 21 with respect to toxicity against hematopoietic stem cells and hepatocytes. Based on its profile, 19 has been selected for clinical trials.

Differential changes in corticospinal and Ia input to tibialis anterior and soleus motor neurones during voluntary contraction in man.

Motor-evoked potentials (MEPs) were recorded in the tibialis anterior and soleus muscles following transcranial magnetic stimulation (TMS) of the motor cortex. In the soleus, the H-reflex amplitude increased with the contraction level to the same extent as that of MEPs, whereas in the tibialis anterior, the H-reflex amplitude increased significantly less than that of MEPs. The latency of the MEPs decreased with contraction, whereas this was not the case of the H-reflexes. In the tibialis anterior, the response probability of single-motor units (SMU) to TMS increased more substantially during voluntary contraction than following stimulation of the peroneal nerve. In the tibialis anterior, the response probability of SMU increased more substantially during voluntary contraction than following stimulation of the peroneal nerve. The short-latency facilitation, presumably monosynaptic of origin, of the soleus H-reflex evoked by subthreshold TMS increased as a function of the plantarflexion force. This was not the case for the heteronymous Ia facilitation of the soleus H-reflex following stimulation of the femoral nerve. It is concluded that the corticospinal input to lower limb motor neurones generated by TMS increases with the level of voluntary contraction, whereas this is true only to a limited extent for the synaptic input from Ia afferents. It is suggested that this reflects changes in the susceptibility of corticospinal cells to TMS during voluntary contraction.

Recruitment of extensor-carpi-radialis motor units by transcranial magnetic stimulation and radial-nerve stimulation in human subjects.

The responses of 34 extensor-carpi-radialis motor units to graded transcranial magnetic stimulation (TMS) and electrical stimulation of the radial nerve were investigated in six human subjects. Simultaneously with the recording of the single motor-unit discharges, motor-evoked potentials (MEPs) and H-reflexes evoked by the two types of stimulation were recorded by surface electrodes and expressed as a percentage of the maximal motor response (Mmax). Ten motor units were activated in the H-reflex when it was less than 5% of Mmax, but not in the MEP even when it was 15% of Mmax. The opposite was observed for three motor units. Eleven motor units were recruited by both stimuli, but with significantly different recruitment thresholds. Only ten motor units had a threshold similar to TMS and radial nerve stimulation. From these observations, we suggest that caution should be taken when making conclusions regarding motor cortical excitability based on changes in the size of MEPs, even when it is ensured that there are no similar changes in background EMG-activity or H-reflexes.

Lectin-Mediated Drug Targeting: Discrimination of Carbohydrate-Mediated Cellular Uptake between Tumor and Liver Cells with Neoglycoconjugates Carrying Fucose Epitopes Regioselectively Modified in the 3-Position.

The circumvention of efficient "carbohydrate traps" in the liver is required for targeting glycoconjugates on tumor cells. As shown in the model system of bovine serum albumin (BSA) conjugates, the nature of R(1)-R(3) of the fucose epitope plays an important role in the discrimination of cellular uptake between tumor and liver cells as well as in the cytotoxic activity.

Hospital financing by self administrated institutions. Proposals for a new form of organization and financing of hospital care in West-Germany.

Acta Hospitalia publishes this summary as an illustration of the difficult process most Western countries experience in reorienting their hospital financing systems. The case of West-Germany is of particular interest. It is the leading economic power in the European Economic Community and its sickness funds (the Krankenkassen) play a very important role in hospital financing. The article reports on the conclusions of a five year study by the R. Bosch Stiftung. We draw attention to the following: The article illustrates that each hospital financing system implies a particul balance of power between the hospitals, on the one hand, and the sickness funds on the other hand, under the auspices of the government. The final balance of power is not so much determined by the general principles but by the detailed operational procedures on which the financing system will eventually be based. This may explain why the conclusions of the Commission are rather vague. The option of the price as the main control instrument immediately demands some 'state committee' to lay down the guidelines for the provision of hospital care including the regional conditions and minimum service quantity and quality standards.

Occupational therapy management of tendon transfers in persons with spinal cord injury quadriplegia.

Upper extremity surgical reconstruction can play an important role In helping the spinal cord injured quadriplegic patient achieve maximum independence in a variety of activities of daily living. The transfer of the brachioradialis to the extensor carpi radialis brevis, the brachioradialis to the flexor pollicis longus, and the posterior deltoid to the triceps each provide opportunities for functional improvement in this patient group. The occupational therapist's understanding of functional potentials and problems unique to spinal cord injury provides a realistic perspective to the team on potential benefits of each surgery. The occupational therapist also plays a critical role in identifying appropriate surgical candidates, in establishing treatment goals with the patient, and in administering a carefully planned post-operative treatment program.

Bacterial communities degrading amino- and hydroxynaphthalene-2-sulfonates.

A 6-aminonaphthalene-2-sulfonic acid (6A2NS)-degrading mixed bacterial community was isolated from a sample of river Elbe water. The complete degradation of this xenobiotic compound may be described by a mutualistic interaction of two Pseudomonas strains isolated from this culture. One strain, BN6, could also grow on 6A2NS in monoculture, however, with accumulation of black polymers. This organism effected the initial conversion of 6A2NS into 5-aminosalicylate (5AS) through regioselective attack of the naphthalene skeleton in the 1,2-position. 5AS was totally degraded by another member of the community, strain BN9. After prolonged adaptation of strain BN6 to growth on 6A2NS, this organism readily converted all naphthalene-2-sulfonates with OH- or NH2-substituents in the 5-, 6-, 7-, or 8-position. The corresponding hydroxy- or aminosalicylates were excreted in stoichiometric amounts, with the exception that the metabolite from 5A2NS oxidation was not identical with 6AS.