MRI and FDG-PET in the assessment of inflammatory aortic arch syndrome in complicated courses of giant cell arteritis.

OBJECTIVES: To evaluate the use of MRI and FDG-PET for the diagnosis and measurement of disease activity of inflammatory aortic arch syndrome in patients with complicated giant cell arteritis. METHODS: MRI and FDG-PET were performed for 25 patients with giant cell arteritis who presented with a complicated disease course despite immunosuppressive therapy. Disease activity of the thoracic aorta and the supra-aortic arteries as assessed by both modalities was compared with serological (C-reactive protein (CRP), erythrocyte sedimentation rate (ESR)) and clinical findings (Birmingham vasculitis activity score (BVAS.2)). Additionally, the usefulness of MRI for assessment of vessel wall thickening, aneurysms and stenoses was evaluated. RESULTS: In 17/25 patients, MRI disclosed structural vessel lesions suspicious for vasculitis. Active disease was detected by MRI, thoracic PET, and whole body PET in 22, 14 and 20 patients, respectively. While serological and clinical findings correlated significantly with each other, there was no concordance with MRI and only low, non-significant correlation of PET with CRP (r(s) = -0.158, 0.136), ESR (r(s) = -0.232, 0.320) and BVAS.2 (r(s) = -0.064, 0.221) for disease activity. CONCLUSIONS: MRI and PET are unreliable for assessing large-vessel inflammation in patients with giant cell arteritis and pre-existing immunosuppressive therapy. MRI is valuable for its ability to detect morphological vessel lesions, such as aneurysms and stenoses.

[Positron emission tomography (PET) in soft-tissue sarcoma]. / Positronenemissionstomographie (PET) beim Weichteilsarkom.

Positron emission tomography (PET) uses the significantly increased glucose metabolism to differentiate malignancies from healthy tissue. This method is well established in the oncologic diagnostics of solid epithelial tumours and also in breast cancer. In low-grade soft tissue sarcomas specificity and sensitivity are limited, however. Not only conventional systems, but also dual headed coincidence cameras requiring considerably less technical and economical expenditure can be used to produce PET-scans. We have studied the outcome of this technology in 13 patients with different types of soft-tissue sarcoma. It is our impression that both conventional and gamma camera based PET-systems result in similar results in soft-tissue sarcoma. Furthermore, in one of the cases presented, PET was able to detect metastases considerably earlier than conventional radiography.

Kinetics and organ distribution of allogeneic natural killer lymphocytes transfused into patients suffering from renal cell carcinoma.

The transfusion of natural killer (NK) lymphocytes into patients suffering from malignant diseases is an approach of current interest in the field of immunotherapy. Little is known about the organ distribution, survival, and clearance of donor immune effector cells in cellular therapy, and no reports exist on these important parameters considering NK cells in particular or any other type of allogeneic lymphocytes in humans. In the context of a clinical Phase I/II study we examined the distribution of transfused allogeneic NK cells in patients suffering from renal cell carcinoma. The NK cells were ex vivo cultivated and activated before transfusion. To assess the circulation of the transfused cells in the peripheral blood, we used a nested PCR technique to detect HLA DRB1 alleles of the NK cell donors. Post-transfusion, all patients showed evidence of circulating donor cells for up to 3 days. After 7 days, all donor cells were cleared from the blood to undetectable levels. To assess organ distribution, (111)In-labeled NK cells were injected and monitored by whole-body scintiscans. A distribution to the whole body, with preference for liver, spleen, and bone marrow, was observed after a short initial uptake in the lungs. No activity was observed in lymphatic nodes. A total of 2/4 evaluable metastases showed a clear accumulation of transfused NK cells. The half-life corrected activity in all body compartments remained almost constant over the 6-day observation period in concordance with the absence of any excretion of radioactivity. This may indicate an extended survival of the transfused cells, despite their foreign nature, in the host organism.

Radioiodine therapy in Graves' hyperthyroidism: determination of individual optimum target dose.

UNLABELLED: The aim of this study was to investigate the results of different volume-dependent target doses on clinical outcome 6 months after radioiodine therapy (RITh) and its correlation with post therapeutic thyroid volumes (Vpost) in patients with Graves' disease. This analysis was designed to determine factors improving the results of radioiodine therapy without increasing target doses generally, as has been recommended recently. We studied consecutive data from 102 patients with Graves' disease, who had initial radioiodine therapy between 1991 and 1995. The 131I activities were calculated according to the formula of Marinelli. In addition to the normal calculation individual target doses were adjusted to the thyroid volumes of each patient before therapy. For statistical evaluation, the patients were divided into three subgroups of comparable sample sizes: Group I included those with a thyroid volume <15 ml before therapy. Group II included those ranging from a 15-25 ml volume before therapy and group III included those with thyroid volumes >25 ml. Laboratory thyroid parameters and thyroid volumes were measured in those groups before and 6 months after therapy. RESULTS: Analysis of all patients revealed a significantly higher rate of hypothyroidism (54%) and fewer cases of hyperthyroidism (15%) six months after therapy in cases with Vpost smaller than 8 ml. The median Vpost needed to achieve an optimum therapeutic success rate (rate of eu- or hypothyroidism) was smaller than 5 ml in group I and smaller than 10 ml in group II. Therapeutic success was associated with different target doses in each group, 150,220 and 260 Gy for groups I, II, and III respectively. CONCLUSIONS: Post therapeutic thyroid volumes correlated significantly with clinical outcome six months after therapy. An adjustment of the target doses based on thyroid volumes before therapy will lead to an appropriate reduction of thyroid volumes. Thus, in the individual case clinical outcome could be improved without applying higher target doses in all patients. This would ensure a better utilization of limited resources in medical care e.g. through a shorter hospital stay.

Investigation of the anti-allergic activity of azelastine on the immediate and late-phase reactions to allergens and histamine using telethermography.

BACKGROUND: Due to the interest in azelastine's diverse modes of action, this study investigated its effects on immediate and late-phase cutaneous allergic reactions using visual methods and telethermography. OBJECTIVE: The aim of the study was to investigate the effect of azelastine on the immediate and late-phase skin reactions using both planimetric evaluation of weal and erythema and a telethermographic technique. METHODS: The study was a double-blind crossover study; medication consisted of one tablet per day for 7 days of either placebo or azelastine 4 mg. Eight allergic patients were assessed on five occasions: prior to treatment, at the end of the first 7-day treatment, after a 21-day washout period, following the second 7-day treatment period and finally following a 2-6 week washout period. Skin prick tests with timothy grass and intradermal tests with Alternaria allergens were performed on the patients' back. In addition, patients were tested with intradermal histamine as a positive control. Surfaces of weal, erythema and infiltration were calculated using computerized planimetry at 0, 20, 40 and 60 min, and 3, 6 and 8 h. Thermographic images were recorded and the thermographic area and the increase in average temperature (DeltaT) were calculated. RESULTS: The coefficient of variation within baseline reactions ranged from 3 to 32% for weal and erythema and from 5 to 25% for thermographically recorded reactions. The stronger the reaction, the more constant the baseline was. Treatment with azelastine (4 mg/os once daily) inhibited immediate reactions to allergens by 65% (range 55-74) and to histamine by 68% (range 47-82). The late-phase reactions to allergens were less well defined and showed larger individual differences in the degree of inhibition caused by azelastine, they were inhibited by 49% (range 32-67). Late-phase reactions to histamine were less intense and could only be detected with thermography; only thermographic units showed a decrease (26%) in response to azelastine. CONCLUSION: This study has confirmed azelastine's histamine-blocking activity. In addition, the late-phase results suggest that azelastine has anti-inflammatory activity. The reproducibility and sensitivity of the thermographic results confirm the usefulness of this technique in immunopharmacology.

Influence of radioiodine therapy on urinary iodine excretion.

AIM: In 214 patients with benign thyroid diseases the time-course of urinary iodine excretion (UIE) was investigated in order to identify changes after radioiodine therapy (RITh). METHOD: UIE was measured photometrically (cerium-arsenite method) and related to urinary creatinine on the first and last day of the radioiodine test and then three days, seven days, four weeks, and six months after 131I administration. RESULTS: As compared with the level found immediately before radioiodine therapy, median UIE had almost doubled four weeks after therapy and was still significantly elevated six months after therapy. This increase correlated significantly with the target volume as measured by scintigraphy and sonography. CONCLUSIONS: The persistent elevation of UIE for months after RITh is a measure of treatment-induced damage to thyrocytes. Therefore, in view of the unfavourable kinetics of iodine that follow it, RITh should if possible be given via a single-dose regime.

Salivary gland scintigraphy using technetium-99m-pertechnetate after autotransplantation of the submandibular salivary gland in the correction of dry eye.

The aim of the study was to determine whether salivary gland scintigraphy using technetium-99m pertechnetate is suitable for checking the vitality and function after autotransplantation of the submandibular salivary gland in patients with dry eye syndrome. To this end, 56 scintigraphic studies in 20 patients have so far been performed. In addition, these scans were evaluated by a region of interest (ROI) technique in order to examine tracer uptake in the early and late stages after surgery. We have been able to prove that in this special respect, too, the salivary gland scintigraphy is suitable for assessing reliably the vitality and function of the transplanted gland. The secretion into the eye and thus the patency of the efferent duct can also be displayed. This proved to be particularly valuable in those cases in which at first no secretion could be seen in the clinical examination. In patients with uncertain excretory function, we were able to distinguish between non-vitality and lack of patency of the secretory duct. Using ROI evaluation, no significant decrease in the salivary function has been detected in long-term follow-up, now extending to 1 year after surgery.

[Esophageal scintigraphy of Zenker's diverticula before and after diverticulotomy]. / Osophagusszintigraphie von Zenkerschen Divertikeln vor und nach Divertikulotomie.

AIM: The filling and evacuation of Zenker's diverticula were scintigraphically examined before and after operation to quantify their functional relevance. These results were correlated with the symptoms of the patients and the findings of the barium swallow x-ray examination using cineradiography. METHODS: Sequential and static esophageal scintigraphies were performed in 17 patients with Zenker's diverticulum before and after laser surgical diverticulotomy. We used a gamma camera system in 45 degrees LAO-position after application of 15 ml of tea which was marked with 99mTc-DTPA. Filling and evacuation of the diverticulum were expressed in proportion to the administered activity. Relative volumes of the diverticula were obtained from cineradiography by using the height of the neighbouring cervical vertebra, and the clinical symptoms were divided into 4 groups. RESULTS: Zenker's diverticula could be verified visually and quantitatively by scintigraphy. The precise temporal course of the reduction of activity in the diverticulum was exactly determined. The scintigraphic retentions correlated with the x-ray volumes with a coefficient ranging from 0.55 to 0.85. Clinical symptoms also were not very closely related to scintigraphic and x-ray findings, respectively. CONCLUSION: The esophageal scintigraphy allows quantification of the filling and evacuation of Zenker's diverticula, thus it is suitable for objectivization of the functional relevance of the diverticula. That's why the esophageal scintigraphy should be taken to the diagnosis of diverticula in addition to the clinic and the x-ray examinations. The method is especially useful to evaluate the results after diverticulotomy.

Comparative effects of a fixed combination of reproterol hydrochloride and disodium cromoglycate with each agent alone on antigen-induced airway responses in sheep.

The purpose of this study was to compare the effectiveness of an eight day treatment with clinically relevant doses of a fixed combination of the beta 2 mimetic reproterol hydrochloride and disodium cromoglycate with each agent given alone against antigen-induced early (EAR) and late airway responses (LAR) as well as post-antigen-induced airway hyperresponsiveness (AHR) in allergic sheep. Animals were treated in a randomized fashion with either the inhaled combination (n = 6), reproterol hydrochloride alone (n = 6), disodium cromoglycate alone (n = 6), or placebo (n = 8). Treatments (two puffs from a metered dose inhaler) were given three times a day for 7 days and once on the 8th day 1 h before airway challenge with Ascaris suum antigen. In the placebo trial, antigen challenge resulted in EAR and LAR as measured by increases in specific lung resistance; these changes were followed 24h later by AHR to inhaled carbachol. With respect to the placebo trial, treatment with reproterol hydrochloride reduced the EAR (P < 0.05) and blocked the LAR (P < 0.05), but had no effect on the post-challenge AHR. Treatment with disodium cromoglycate also reduced the EAR (P < 0.05), blocked the LAR (P < 0.05), and blocked the post-antigen-induced AHR (P < 0.05). Treatment with the fixed combination reduced the EAR (P < 0.05), blocked the LAR (P < 0.05), and blocked the post-antigen-induced AHR (P < 0.05). Comparison of the different agents indicated that the fixed combination gave significantly increased protection against the EAR than either agent alone, gave slightly better (P < 0.05) protection against the late response than cromolyn sodium and gave better protection against post-antigen-induced AHR than reproterol hydrochloride alone. These results suggest that a fixed combination of a beta 2-mimetic and disodium cromoglycate provides some increased protection against antigen-induced airway responses when compared to either agent alone in a controlled laboratory setting.

Evaluation of the drug monitoring programme of azelastine hydrochloride nasal spray in the treatment of allergic rhinitis in children under 13 years of age.

The efficacy and safety of a nasal spray containing azelastine (CAS 58581-89-8; e.g. Afluon, Allergadil, Rhinolast) in the treatment of both perennial and seasonal allergic rhinitis have been evaluated in two postmarketing drug surveillance programmes (PMS) conducted in Spain. The present analysis reports on the data from a subpopulation from these studies and includes 211 children aged less than 13 years of age. In 73% of children the administered dose of azelastine was one spray puff per nostril twice daily, corresponding to the recommended daily, dosage of 0.56 mg azelastine. Patients with seasonal rhinitis were treated for a period of two weeks, those perennial rhinitis were treated for four weeks. The efficacy of the azelastine was assessed by the changes in severity of the following 10 individual symptoms of rhinitis: sneezing, nose itching, nose congestion, rhinorrhoea, smell reduction, eye itching, lachrimation, photophobia, throat itching, and coughing. Symptoms were rated according to a four-point scale: 0 = absent, 1 = slight, 2 = moderate, and 3 = severe. Both the investigators and the patients were requested to evaluate efficacy and tolerance according to a four point scale: 1 = very good, 2 = good, 3 = moderate, 4 = bad. All of the 10 clinical symptoms underwent a statistically significant and clinically relevant reduction during the treatment period. Nose itching, sneezing, and rhinorrhoea were the symptoms which completely disappeared in the highest number of patients by the end of therapy. The mean sum of all 10 symptom scores pre-treatment (baseline visit) was 11.03 while at the completion of therapy (control visit) it was 3.21. Overall, a decrease of this score was seen in 112 (98%) patients for whom complete data was available, whereas an increase was registered only in 2 (2%) cases. The mean total of the five nasal scores at the baseline visit was 7.64, and at the control visit its value measured 2.31. One hundred and twenty-one (98%) patients exhibited a decrease in the total nasal score, and only 3 (2%) demonstrated an increase. The mean total of the three ocular symptoms scores at the baseline visit was 2.25, while at the control visit its value was only 0.48. A decrease in the total ocular score was observed in 78 (62%) patients, while an increase occurred in only one patient. Overall, 85% of doctors evaluated the efficacy of the drug as "very good/good". 90% of patients did not report adverse events (AEs) during treatment with azelastine and only four patients discontinued treatment due to AEs. General tolerance was evaluated as "very good or good" by 97% of the treating physicians. Local tolerance was rated as "very good or good" by 94%. The most positive characteristics of the therapy according to the physicians were: rapid onset of action in 56% of cases, good efficacy in 46%, simple application in 44%, no sedation in 34%, and long duration of action in 22% of cases. Based upon the excellent risk-benefit assessment of this PMS, our results confirm the suitability of azelastine nasal spray in the treatment of allergic rhinitis in juvenile patients.

Efficacy and tolerability of azelastine nasal spray in the treatment of allergic rhinitis: large scale experience in community practice.

Two Spanish prospective monitoring studies evaluated efficacy and tolerability of azelastine nasal spray containing azelastine hydrochloride for allergic rhinitis. Both studies were conducted by community practitioners over two weeks (Study I) or one month (Study II). The numbers of patients recruited were 3680 (I) and 4002 (II). Of these, 56.1% (I) and 51.7% (II) had been previously treated with oral antihistamines with/without other medications. Patients rated the severity of 10 symptoms of allergic rhinitis as absent, mild, moderate or severe. Azelastine nasal spray was generally administered at a dose of one spray puff (0.14 mg) per nostril twice daily. Follow-up was after 14 days (I) or 31 days (II), when symptoms were rated and patients questioned about treatment. Assessment was by a sum score for all 10 symptoms. A symptom sum score of 16-20 occurred in 21.1% (I) and 13.7% (II) of patients before treatment and only 0.8% (I) and 0.6% (II) after treatment. A symptom sum score of 11-15 occurred in 35.9% (I) and 30.5% (II) of patients before treatment and only 2.6% (I) and 2.8% (II) after treatment. Overall, 92.3% (I) and 90.7% (II) of patients were completely free of adverse events, 7.0% (I) and 8.8% (II) experienced one and 0.7% (I) and 0.6% (II) two adverse events. The number of doctors who rated efficacy as either very good or good was 89.4% (I) and 84.6% (II). General tolerance was rated as good or very good by 97.5% (I) and 97.3% (II), and local tolerance by 93.1% (I) and 91.5% (II) of physicians, respectively. Overall, azelastine nasal spray was highly effective and very well tolerated in normal clinical practice.

Topical therapy of allergic rhinitis in childhood: Allergodil nasal spray--non-sedating in children.

The efficacy and safety of the nasally administered drug Allergodil in the treatment of allergic rhinitis were evaluated in a prospective drug monitoring programme conducted in Germany. Data from 489 children under the age 13 were included. The study was designed to gain knowledge about Allergodil in a normal clinical setting. Dosing was at the judgement of the investigator bearing in mind data sheet recommendations, i.e. one spray-puff (0.14 mg) per nostril twice daily. Patients were treated for four weeks. The occurrence of ten nasal, eye and throat symptoms was rated (0 = never, 1 = sometimes, 2 = often). All symptoms showed a statistically significant improvement at the final visit, as did the overall sums of the scores. These changes were clinically significant. Overall assessment of efficacy by the physicians and the patients was very good and good in more than 85% of patients. 70% of patients required no concomitant medication. 13.5% of patients experienced adverse events, mostly mild or moderate in severity. Safety and tolerance were assessed as very good and good in more than 97% of cases. No sedation was seen. With respect to both efficacy and safety, there were no differences between patients younger than 6 years and those aged 6-12 years. In conclusion, these results suggest that Allergodil is an effective treatment of the symptoms of allergic rhinitis in children. The subgroup of 48 young patients studied shows that Allergodil was safe and well tolerated in patients aged 2-6 years.

[The value of scintigraphic functional assessment in extreme hydronephrosis]. / Wertigkeit der szintigraphischen Funktionsberechnung bei extremer Hydronephrose.

Renographic studies are occasionally suspected of overestimating the excretory function of obstructed kidneys. Presenting the case of a ten months old boy with obstruction of the ureterovesical junction and severe hydronephrosis, we discuss the validity of the assessment of renal function by radionuclide urography. Normal postoperative excretion as well as renographic controls confirmed the good relative function of the hydronephrotic kidney. Instead of nephrectomy a reconstructive operative procedure was employed.

[An iterative strategy for determining the source distribution in single photon tomography using a rotating gamma camera (SPECT)]. / Eine iterative Strategie zur Bestimmung der Quellverteilung bei der Einzelphotonen-Tomographie mit einer rotierenden Gammakamera (SPECT).

A new iterative strategy for determination of the source distribution in single-photon emission tomography (SPECT) simulates mathematically the scintigraphic imaging process during direction sum computation. Limited spatial resolution and gamma-ray attenuation are taken into account using simplifying approximations. Highly resolved low-noise tomograms without obvious artifacts are obtained. Results of phantom measurements as well as cases of thyroid and brain perfusion imaging are presented to demonstrate the capabilities of the method.

Thyroid autonomy: sensitive detection in vivo and estimation of its functional relevance using quantified high-resolution scintigraphy.

This study is concerned with 236 euthyroid individuals living in an area of iodine deficiency, 227 of whom had endemic goitres. In these subjects, autonomy could be suspected owing to an inhomogeneous activity distribution on the thyroid scintigram or a subnormal TSH response to TRH. They complete a total number of 426 investigated individuals. Previously, in 190 separated controls without evidence of autonomy, the reference ranges for the thyroid 99mTc pertechnetate uptake under suppression (TcUs), a measure for the non-suppressible thyroid iodide clearance, and for suppressibility of circumscribed thyroid regions, had been determined. These two parameters obtained by high-resolution quantified scintigraphy were used for an accurate detection of thyroid autonomy among the 236 individuals. Suppression scintigraphy revealed autonomy in 171 patients. delta TSH after TRH was subnormal in 40% of the subjects with abnormal thyroid suppressibility. Prevalence of abnormal suppression was dependent on three factors: patient age, goitre type and estimated thyroid weight. In the total investigated collective, the prevalence of autonomy was 77% in patients with a goitre weight above 50 g. The individuals with abnormal suppression were grouped into four classes of TcUs. In these classes, free thyroxine index (FT4I) and total triiodothyronine (TT3) increased with increasing TcUs, whereas delta TSH decreased. This finding indicates a continuum of different extents of autonomous thyroid function, whereas in the individual patient, the extent can be determined using the pertechnetate uptake under suppression. In addition, FT4I, TT3 and delta TSH in each of the TcUs classes depended on the individual iodine supply.(ABSTRACT TRUNCATED AT 250 WORDS)

Physiological aspects of the thyroid trapping function and its suppression in iodine deficiency using 99mTc pertechnetate.

In an area of iodine deficiency, we investigated 190 individuals with and without euthyroid endemic goitre, who had a normal TSH response after TRH and an entirely homogeneous thyroid scintigram before and under suppression. In these subjects, the thyroid uptake of 99mTc pertechnetate, as a measure of the iodide trapping function, was determined before (TcUb) and under suppression (TcUs), using quantitatively evaluated scintigraphy. In this control group of individuals, without evidence of autonomy, the reference ranges of TcUb and TcUs were determined. The upper limit of the reference range for TcUb was 7.4% of the tracer activity injected, and for TcUs 1.6%. The reference range of TcUs is to be used to detect accurately thyroid autonomy in vivo. In addition, factors affecting the thyroid trapping function were investigated. With decreased iodine supply, trapping before suppression was increased, compensating for iodine deficiency. The effect of TSH on the trapping function was secondary, indicating that, to a considerable degree, the follicular cells adapt their iodide trapping to the iodine supply. The trapping before and under suppression increased with the estimated thyroid weight. delta TSH after TRH stimulation measured before suppression correlated inversely with the trapping under suppression. The two latter observations suggest that there is a continuum between low and increased levels of the TSH-independent thyroid function, even among these selected individuals without primary evidence of autonomous tissue. A correlation of the trapping function with sex, oestrogen treatment, and goitre type was not demonstrable. Age was found to have a small influence. Except for iodine contamination, the factors affecting the pertechnetate uptake of the thyroid, can be neglected under routine conditions.

Iterative reconstruction of thyroidal SPECT images.

First SPECT results using a multiplicative iterative reconstruction algorithm are presented. The superiority of the iterative technique over filtered backprojection is demonstrated in two thyroid SPECT studies. Obvious benefits of the new reconstruction technique are better defined outlines of the imaged organ and patient body as well as negligible artificial image amplitudes outside the patient.

[Correlation of scintigraphic and x-ray findings in Marie-Bamberger secondary hypertrophic osteoarthropathy]. / Korrelation szintigraphischer und röntgenologischer Befunde bei der sekundären Osteoarthropathia hypertrophicans Marie-Bamberger.

The radiological and scintigraphic findings in the rare condition of hypertrophic osteoarthropathy (Marie-Bamberger) were followed up for a period of two years. They are described and compared. Skeletal scintigraphy shows the abnormalities in the skeleton at an earlier stage than does radiology and also shows more extensive manifestations. The specific symmetrical distribution of abnormally increased uptake in the diaphyses and metaphyses of the long bones of the extremities, with sparing of the axial skeleton, produces highly specific appearances which can be considered as diagnostic.