Evaluating thyroid gland function in patients with protein anomalies

The euthyroid hyperthyroxinemia (EHT) is characterized on the one hand by a normal basal THS or TRH-TSH response but also by high plasma values of total thyroxine (TT4) on the other. However if only TT4 is assessed, "hyperthyroidism" may be diagnosed erroneously. EHT may be caused by an increase of specific thyroxine binding proteins which may be hereditary (permanent) or acquired (transient). The most frequent disturbance is due to an estrogen induced increase of thyroxine binding globulin (TBG) in the course of pregnancy, anticonceptive drugs or estrogen treatment. The albumin associated HT (FDH syndrome), first reported in 1979, has autosomal dominant traits. 144 patients with FDH syndrome were observed during the period between 1984 and 1990, i.e. 7% (1986) of all hyperthyroid patients explored. Family screening is required to prevent unjustified treatment. Additionally existing disturbances of thyroid function as well as other protein binding anomalies may both cause problems in differential diagnosis. Prealbumin associated hyperthyroxinemia (PAAH), first published in 1982, may be due to an inherited increase in affinity, but may also be the consequence of a true elevation of prealbumin plasma concentration in the course of an islet cell cancer; both conditions are extremely rare. Nearly as rare are patients with plasma autoantibodies directed against T4 and/or T3 (5 cases); yet, a reverse T3 autoantibody could be observed in merely 1 case. By means of our modified radio-thyroxine-agarosegel-iceelectrophoresis all such protein anomalies may be diagnosed and differentiated in 1 procedure. Moreover, all other types of EHT must be taken into consideration by differential diagnosis.     

Neuroleptic influence on hyperthermia induced by 5-hydroxytryptophan and p-methoxy-amphetamine in MAOI-pretreated rabbits

5-Hydroxytryptophan (5-HTP) and p-methoxyamphetamine (p-MA) induced dose-dependent, lethal hyperthermia when applied intravenously to monoamine oxidase inhibitor (MAOI) pretreated rabbits. The time course of hyperthermia and the doses required to induce hyperthermia varies between the two substances. Results with -MT and PCPA suggest that 5-HTP hyperthermia depends on 5-HT formation, release of endogenous 5-HT, and the presence of catecholamines, whereas p-MA-induced hyperthermia most likely is a result of indirect 5-HT release.Some neuroleptics (piflutixol, spiroperidol and methiotepine) are extremely potent inhibitors of the induced hyperthermia. Also the 5-HT receptor blocking agent methergoline antagonizes hyperthermia induced by the two substances in rather low doses. On the other hand cis (Z)-flupenthixol is a very weak antagonist of 5-HTP but a more potent inhibitor of p-MA hyperthermia. It is concluded that both 5-HT and catecholamine (dopamine) receptor blockade is required to antagonize 5-HTP hyperthermia and that antagonism of p-MA induced hyperthermia is primarily a result of influence on the 5-HT system.Part of this work was presented at the 7th International Congress of Pharmacology, Paris, 1978     

Sprachstörungen und Dyskinesien als Initialsymptome einer kortikobasalen Degeneration

The article describes the development of symptoms in a 59-year-old patient. Dyskinesia and speech disorder were the only clinical features in the beginning. Increased immunological parameters and only slight hypokinetic-rigid signs for a long time made the diagnostical and therapeutical process more difficult, as well as atypical findings in neuroimaging techniques. Corticobasal degeneration was diagnosed about 6 years after onset of clinical symptoms.     

Comparison between 99mTc-tetrofosmin/pertechnetate subtraction scintigraphy and 99mTc-tetrofosmin SPECT for preoperative localization of parathyroid adenoma in an endemic goiter area

RATIONALE AND OBJECTIVES: Technetium-99m-((99m)Tc-) tetrofosmin, a cationic, lipophilic complex like (99m)Tc-sestamibi, has proved to be a potential tracer for parathyroid scintigraphy despite some differences in washout behavior from the thyroid gland. Previous results comparing a double-phase technique with single-proton emission computed tomography (SPECT) or with subtraction techniques demonstrated a high detection rate, especially when SPECT and subtraction techniques were used, whereas the double-phase protocol revealed only moderate results. In this study, a direct comparison was made between (99m)Tc-tetrofosmin/pertechnetate subtraction and SPECT to elucidate the optimal protocol for tetrofosmin parathyroid imaging. METHODS: Twenty-three patients who were biochemically suspected of parathyroid adenoma or hyperplasia due to primary or tertiary hyperparathyroidism were included in our study. In all patients, serum calcium, phosphate, and intact parathormone levels were analyzed in a single blood sample before (99m)Tc-tetrofosmin/pertechnetate subtraction scintigraphy and SPECT. Ultrasound of the neck was performed in all patients to exclude false-positive results due to thyroid adenomas. All patients underwent parathyroidectomy with intraoperative revision of all parathyroid glands, and the histological results were compared with preoperative findings. RESULTS: Both imaging modalities, ie, subtraction scintigraphy and SPECT, correctly identified 20 of 23 (87%) histologically confirmed adenomas preoperatively. The positive predictive value was calculated to be 95% and 100%, respectively, for these two methods. Subtraction scintigraphy and SPECT showed concordant results in 19 patients (18 positive, 1 false-negative) and discordant results in 4 patients (2 positive with subtraction, 2 with SPECT). The combined use of subtraction scintigraphy and SPECT techniques revealed a sensitivity of 95.7% (22/23) and a positive predictive value of 95%. The whole procedure can be performed in less than 90 minutes per patient. Whereas subtraction scintigraphy tended to show more false-positive retentions due to thyroid adenomas, the interpretation of SPECT may be difficult in small adenomas with missing thyroid/parathyroid differential washout. CONCLUSIONS: Both imaging modalities, subtraction scintigraphy with pertechnetate and SPECT, are highly sensitive methods for parathyroid adenoma localization with (99m)Tc-tetrofosmin. However, our study did demonstrate that a combination of both modalities can further improve the diagnostic accuracy. Especially in an endemic goiter area, additional ultrasound may be required to avoid false-positive results due to thyroid adenomas.     

Phase II study of pemetrexed in breast cancer patients pretreated with anthracyclines.

BACKGROUND: To assess antitumor activity and toxicity of pemetrexed in metastatic breast cancer (MBC) patients previously treated with anthracyclines. PATIENTS AND METHODS: Seventy-seven MBC patients from 12 European institutions were entered into the study. Seventy-two patients were considered evaluable for response and toxicity. Forty-two patients were classified as anthracycline-failure (relapse >30 days after completion of a prior anthracycline regimen) and 30 as anthracycline-refractory (progression within 30 days after anthracycline therapy). Pemetrexed 600 mg/m(2) was administered intravenously every 3 weeks until progressive disease or unacceptable toxicity. RESULTS: There were three complete and 12 partial responders [response rate 21% (95% confidence interval 12%)]. Response rates in the anthracycline-failure and anthracycline-refractory groups were 24% and 17%, respectively. A subset of 31 patients pretreated with anthracyclines and taxanes had a response rate of 26%. Median duration of response and median survival were 5.5 and 10.7 months, respectively (13 months in the failure group and 5.7 months for refractory). Grade 3/4 toxicities included neutropenia and thrombocytopenia in 56% and 19% of patients, respectively. Nine patients (12%) experienced neutropenic fever. Grade 3/4 non-hematological toxicities included skin rash (10%), nausea (12%), fatigue (10%) and stomatitis (5%). CONCLUSION: Our trial demonstrates pemetrexed to be active in breast cancer, with manageable toxicity. Activity of pemetrexed did not appear to be adversely affected by prior taxane, 5-fluorouracil or endocrine treatments.     

Abnormalities on chest radiographs following radiation therapy for breast cancer

The aim of this study was to study pulmonary radiological abnormalities with chest radiography following different radiotherapy (RT) techniques for breast cancer with respect to regions and density, and their association with pulmonary complications and reduction in vital capacity (VC). Chest radiographs were performed 5 months following local or loco-regional RT in 167 breast cancer patients. The radiological abnormalities were analysed with a classification system originally proposed by Arriagada and evaluated according to increasing density (0–3) and affected lung regions (apical–lateral, basal–lateral, central–parahilar). The highest-density grades in each region were added together to form scores ranging from 0 to 9. The patients were monitored for RT-induced pulmonary complications. The VC was measured prior to and 5 months following RT. An independent evaluation of 51 patients was performed by a second radiologist to control the reproducibility of the classification system. Increasing scores were associated with loco-regional RT and pulmonary complications (P < 0.001). The mean reduction of VC for patients scoring 0–3 (–30 ml) vs 4–9 (–161 ml) was not statistically significant (P = 0.10). Scores of 4–9 were more frequently observed in older patients (P < 0.001). The independent evaluations by two radiologists revealed good agreement (P < 0.001) and no systematic inter-observer variation. Radiological abnormalities on chest radiographs, scored according to Arriagada, can be used as an objective end point for RT-induced pulmonary side effects in breast cancer. Received: 4 February 1999; Revision received: 1 April 1999; Accepted: 5 May 1999     

The influence of human intervertebral disc tissue on the metabolism of osteoblast-like cells

Extensive studies have been performed to evaluate different factors that may affect on spinal interbody fusion, but the role of intervertebral disc tissue in the fusion process remains unclear. To study the influence of intervertebral disc tissue on osteoblast metabolism, we harvested disc tissue from patients who had undergone spinal surgery. The nucleus pulposus and annulus fibrosus were separately co-cultured with osteoblast-like cells SaOS-2 by means of culture inserts or organ culture. We assayed alkaline phosphoatase activity, 3H-thymidine incorporation into the DNA, and production of collagen type I, IL-1beta, IL-6, IL-10, and TNF-alpha. Exposure of the nucleus pulposus (NP) to osteoblast-like cells revealed stimulation of alkaline phosphatase production, 3H-thymidine incorporation and collagen type I production. Exposure of the annulus fibrosus (AF) stimulated 3H-thymidine incorporation and collagen type I production, but did not affect ALP activity. IL-6 was detected after application of NP and AF. Interleukin IL-10, IL-1beta and TNF-alpha were all below detection levels after application of disc tissue. Our findings show that frozen disc tissue stimulates the metabolism of osteoblast-like cells in vitro.     

Validity of a questionnaire survey: the role of non-response and incorrect answers

Errors in questionnaire surveys are usually of one of two sources: non-responses or incorrect answers. The aim was to investigate the validity of a questionnaire survey and to estimate the respective bias of these answers. Of 9,283 subjects selected to receive a questionnaire by post, 3,949 (43%) responded, and, of these, 3,400 correctly reported their Swedish social security number. Answers in the questionnaire survey were given as proportions of the claims registered at local insurance offices. In the group of respondents who had correctly reported their social security number, the answers were compared individually with the registrations in dental insurance claims. In Sweden, these claims are labeled with the patient's social security number and it is thereby possible to make such comparisons. It was shown that errors were caused by non-response and also by respondents giving incorrect answers. Incorrect answers accounted for approximately one-third of the total bias. The remaining bias was caused by a non-response error. It is concluded that questionnaire studies have a bias caused by both non-response and incorrect answers and that together these can be substantial. Scientific reports that include questionnaire surveys must describe the procedure carefully. If possible, other sources of information should be considered.     

« Le syndrome du bébé secoué : les séquelles ? »

The Shaken Baby Syndrome (SBS) is a severe inflicted brain injury due to an adult violently shaking an infant. Diagnostic guidelines have been recently published by the “Haute Autorité de santé”. The mortality rate after SBS is 21.6 % and the long-term outcome is good for only 8 to 36 % patients followed over more than 5 years. The aim of this article is to describe sequelae after a SBS, their mechanisms, prognostic factors and recommendations for a better long-term care of the patients.