Aclarubicin in advanced thyroid cancer: a phase II study.

Twenty-four patients with metastatic thyroid cancer were treated with aclarubicin intravenously at a dose of 25-30 mg/m2 daily for 4 days and treatment was repeated every 3 weeks. None of the patients had previously received chemotherapy. Twenty-three patients received two or more treatment cycles and were evaluated for their response. One complete remission and four partial remissions were noted (objective remission rate 22%). Mean survival time was 57 weeks. Side-effects were evaluated in 24 patients with 18 patients receiving prophylactic antiemetic therapy. Nausea was observed in 18 (75%) and vomiting occurred in three patients (13%). In 15 patients (63%) there was mild myelosuppression. We conclude that aclarubicin alone represents an effective therapy in patients with metastatic thyroid cancer and that side-effects are minor.

Single photon emission computed tomography in AIDS dementia complex.

Single photon emission computed tomography (SPECT) studies were performed in AIDS dementia complex using IMP in 12 patients (and HM-PAO in four of these same patients). In all patients, SPECT revealed either multiple or focal uptake defects, the latter corresponding with focal signs or symptoms in all but one case. Computerized tomography showed a diffuse cerebral atrophy in eight of 12 patients, magnetic resonance imaging exhibited changes like atrophy and/or leukoencephalopathy in two of five cases. Our data indicate that both disturbance of cerebral amine metabolism and alteration of local perfusion share in the pathogenesis of AIDS dementia complex. SPECT is an important aid in the diagnosis of AIDS dementia complex and contributes to the understanding of the pathophysiological mechanisms of this disorder.

[Radioactivity levels of the air inhaled by personnel of a radioiodine therapy unit]. / Aktivitätskonzentration der vom Personal einer Radiojodtherapiestation eingeatmeten Luft.

The mean activity concentration of 131I during inhalation by the nuclear medicine personnel was measured at therapeutic activity applications of 22 GBq (600 mCi) per week. The activity concentration reached its maximum in the exhaled air of the patients 2.5 to 4 hours after oral application. The normalized maximum was between 2 X 10(-5) and 2 X 10(-3) Bq X m-3 per administered Bq. The mean activity concentration of 131I inhaled by the personnel was 28 to 1300 Bq X m-3 (0.8 to 35 nCi X m-3). From this the 131I uptake per year was estimated to be 30 to 400 kBq/a (mean = 250, SD = 50%). The maximum permitted uptake from air per year is, according to the German and Austrian radiation protection ordinances 22/21 microCi/a (= 8 X 10(5) Bq/a). At maximum 50% and, on the average, 30% of this threshold value are reached. The length of stay of the personnel in the patient rooms is already now limited to such an extent that 10% of the maximum permissible whole-body dose for external radiation is not exceeded. Therefore, increased attention should be paid also to radiation exposure by inhalation.

[Plasmapheresis treatment in 3 simultaneously occurring autoimmune diseases: Hashimoto thyroiditis with hyperthyroidism, autoimmune thrombopenia and autoimmune hemolytic anemia]. / Plasmapheresebehandlung bei 3 simultan auftretenden Autoimmunerkrankungen: Hashimoto-Thyreoiditis mit Hyperthyreose, Autoimmunthrombopenie und autoimmunhämolytische Anämie.

A 49 year-old women with a 2-year history of a Coombs-positive autoimmune haemolytic anaemia was hospitalized with Hashimoto's thyroiditis and thyrotoxic crisis. The clinical course was further complicated by an autoimmune thrombocytopenia. Primary resection of the thyroid thus seemed to be too risky, so we decided to perform therapeutic plasma exchange. This led to clinical improvement, enabling us to perform a thyroidectomy. The present investigation reveals the high efficiency of plasmapheresis in the treatment of combined autoimmune diseases. Therapeutic plasma exchange resulted in a reduction of both the relevant autoantibodies and the level of circulating thyroid hormones.

[The behavior of free thyroxine and triiodothyronine concentrations after short-term balanced inhalation anesthesia]. / Das Verhalten der freien Thyroxin- und Trijodthyronin-Serumkonzentrationen nach kurzandauernden balancierten Inhalationsnarkosen.

Acute changes involving the hormones thyroxine (T4) and triiodothyronine (T3) followed by hyper -or hypothyroid crises will lead to both cardiovascular and metabolic disorders. Due to highly sensitive mechanisms controlling central hormonal production and peripheral enzymatic conversion (c.g. T4 to T3), numerous pharmacologically effective substances will influence the kinetics of these hormones. Thus, agents routinely used in anesthetic practice and their metabolites may disturb hormonal regulation in particular due to their central effectiveness [1, 2,5-7]. Based on this premise, it was our goal to search for anesthetic-induced hormonal changes in euthyroid patients living in a goiter-endemic area scheduled for short, elective orthopedic operations. Investigations were done in 21 outpatients (mean age: 24 years, mean body wt.: 64 kg) undergoing minor surgical procedures of the extremities. No clinical signs of thyroid disturbances could be observed preoperatively in the patients. Immediately after intravenous premedication (meperidine HCl 0.75 mg/kg and atropine 0.25 mg), anesthesia was induced (thiopentone 5 mg/kg) and continued by inhalation via face; mask using volatile agents: halothane, isoflurane, or enflurane (O2: N2O; FiO2 = 0.33). According to the anesthetic agent administered (halothane, isoflurane, enflurane), patients were divided into three groups of 7 patients each as listed in Table 1. Blood samples to determine free serum T4 (fT4) and T3 (fT3) as an expression of biologically available T4/T3, unconjugated to transport globulins, were drawn twice: immediately before premedication; and postoperatively after the patient had regained consciousness.(ABSTRACT TRUNCATED AT 250 WORDS)

In situ immune complexes, lymphocyte subpopulations, and HLA-DR-positive epithelial cells in Hashimoto thyroiditis.

Surgical specimens from thyroid glands from seven patients with Hashimoto thyroiditis and two patients with non-autoimmune colloid goiter were analyzed by immunohistologic techniques (direct and indirect immunofluorescence and immunoperoxidase tests) using polyclonal antisera against total immunoglobulin, Ig classes (IgM, IgD, IgG, and IgA), and complement component C3 and monoclonal antibodies specific for B cells, T cell subpopulation, macrophages, natural killer cells, granulocytes, and HLA-DR antigen. Complement-fixing immune complexes (IgG+, C3+) were noted predominantly in areas with only slight destruction and only moderate lymphoid infiltration of thyroid follicles. In areas with intense lymphoid infiltration of thyroid follicles, where many well-developed germinal centers and significant perivascular lymphoid infiltration were seen, immune complexes were scarce. In these latter areas T helper cells (OKT4+, Leu3a+), were more abundant than T cytotoxic/suppressor cells (OKT8+), macrophages (OKM1+), and plasma cells (IgG+); only a few B lymphocytes (smIgM+, smIgD+), granulocytes (ViMD5+), and natural killer cells (VEP13+, Leu7+) were noted in the interstitium between thyroid follicles, intruding between thyroid follicular epithelial cells and merging into the thyroid follicular lumen. Many activated T cells (OKT10+, HLA-DR+) were present in these areas of advanced destruction. HLA-DR antigen expression was seen on macrophages, tissue reticulum cells, vascular endothelial cells, lymphoid cells, and, most interestingly, on thyroid epithelial cells. Normal thyroid epithelial cells did not express HLA-DR. Only a few epithelial cells in the vicinity of lymphoid infiltrations were HLA-DR+ in early stages of Hashimoto thyroiditis, and the number of HLA-DR+ epithelial cells was significantly increased in advanced stages of the disease. In our present report the potential role of HLA-DR+ thyroid epithelial cells for the in situ stimulation of the immune system within the thyroid gland of patients with Hashimoto thyroiditis is discussed, and it is hypothesized that HLA-DR+ thyroid epithelial cells may be an important factor for the progression and self-perpetuation of the disease, which is probably initiated by humoral components of the immune system but further propagated by cellular immunopathologic mechanisms.

Prognosis of renal transplant function by renography with radioactive hippuran.

The relation of the functional prognosis of a kidney graft to the results of renography with radioactive hippuran (OIH-RG) was assessed in 96 patients after renal allograft transplantation in 1982. By October 1, 1984 26 of these kidneys had lost their function. The curves obtained from the gamma-camera OIH-RG are classified into six different curve patterns (curve types 1 to 6) as published earlier. For the evaluation of the long-term prognosis, the survival times of the kidneys were related to the curve types. The distribution of the curve types obtained in patients with a kidney survival longer than 144 weeks differs significantly from the curve type distribution when the kidney survival is shorter than 144 weeks. The individual survival times in the collective 26 lost kidneys show a relation to the different curve types. All kidneys with curve type 4 in the last examination before hospital discharge are lost within the first 20 weeks while curve types 1 and 2 promise a functional survival up to 144 weeks. Serum creatinine time courses and their relation to the OIH-RG curve patterns are analyzed by analyses of variance and covariance with repeated measurement. These statistical analyses reveal significant differences between the creatinine courses in the single curve types and, in addition, a significant interaction of the curve types with the creatinine courses. In curve type 1, a rapid normalization of an elevated creatinine level can be predicted, while in curve type 4 no improvement of the creatinine level and thus of kidney function can be expected at least within the five days following discharge.(ABSTRACT TRUNCATED AT 250 WORDS)

Nephrography with radioactive hippuran in transplanted kidneys: interpretation, limitations, and usefulness.

A total of 485 nephrographies (NGs) performed on 95 patients in 1982 were analyzed statistically. The different modes of orthoiodine-hippuran (OIH) handling by the transplanted kidneys are summarized by six different basic curve patterns. The formation of these patterns is an effect of the prolongation of the time to the curve maximum, the time to 75% of the maximum, and the time until the intersection of the bladder and kidney curves. Also, intraparenchymal retention of activity leads to changes in the OIH curves. The basic curve patterns were correlated with the increase of serum creatinine levels, and thus, OIH-NG has to be interpreted as a differentiated marker of renal function. Renal-transplant rejection does not produce a specific pattern of OIH curve, as seen from comparison of the curve-type distribution in rejection and non rejection periods (chi 2 = 0.0866). The diagnostic values of the OIH is limited to purely functional statements, allowing only an indirect diagnosis of renal-transplant rejections without permitting the differential diagnosis of other causes of renal disturbance. OIH-NG is useful for monitoring renal function because it resolves different function levels very sensitively even at identical creatinine values. Furthermore, it makes it possible to estimate the prognosis of renal functional improvement when creatinine levels are elevated.

Hyperthyroidism due to a TSH secreting pituitary adenoma: case report, treatment and evidence for adenoma TSH by morphological and cell culture studies.

A 36-year-old woman with recurrent hyperthyroidism, inappropriately elevated serum TSH, and an 8 mm pituitary microadenoma is described. Transsphenoidal adenomectomy rapidly reduced serum TSH to normal and restored the euthyroid state with retention of other anterior pituitary functions. Tissue removed at operation was examined by light and electron microscopy and cell culture. The tissue was neoplastic, composed of irregular often elongated cells which immunostrained positively only with antisera to beta-TSH. The cells contained small granules (100-170 nm) usually along the cell membrane. In cell culture TSH alone was secreted and the rate of secretion declined with time. We conclude that the patient had a TSH secreting microadenoma as a cause of her hyperthyroidism.

[Value and indication for isotope reflux cystography in children]. / Aussagekraft und Indikation der Isotopen-Refluxcystographie im Kindesalter.

65 children with recurrent urinary infections were investigated by a reflux-cystography method, using 99mTc labelled millimicrospheres. Our results show that this method allows a clinically sufficient diagnosis of reflux. The radiation exposure of the patient is 50-200 times less than the established reference method (X-ray refluxcystography). However, the amount of reflux, i.e. the stage of disease can only be determined by the radiologic method. On the basis of our results it is therefore recommended to use the radionuclide reflux-cystography method as basic investigation and for follow-up. If the basic investigation shows a reflux classification of the reflux has to be evaluated by X-ray reflux-cystography.

[Concentrations of the main lipoprotein density classes in disturbances of thyroid function in man (author's transl)]. / Plasmalipoproteine bei Störungen der Schilddrüsenfunktion des Menschen.

The concentrations of the main lipoprotein density classes and the postheparin lipolytic activity (PHLA) were determined in the plasma of 12 hyperthyroid and eight hypothroid patients in comparison with 12 euthyroid, metabolically healthy individuals. Low-density lipoproteins (LDL) and high-density lipoproteins2 (HDL2) were decreased in hyperthyreosis (p less than 0.01) and increased in hypothyreosis (p less than 0.01). No significant differences could be detected with respect to the concentrations of very low-density lipoproteins (VLDL) as well as for HDL3, whereas intermediate-density lipoproteins (IDL) were higher in hypothyreotics than in controls (p less than 0.05). PHLA was increased in hyperthyreosis (p less than 0.01) and decreased in hypothyreosis (p less than 0.01). The chemical composition of LDL and HDL2 as well as the apolipoprotein composition of the protein moiety of HDL2 in hyperthyreosis and in hypothyreosis did not significantly differ from those in the control group. When data from all individuals studied were analyzed, no significant relationship could be detected between the concentrations of VLDL and HDL2, whereas HDL2 and PHLA correlated in a negative manner (p less than 0.05). It is suggested that HDL2, in addition to LDL, acts as carrier protein for the cholesterol increasingly yielded in hypothyreosis.

[Plasma filtration treatment in thyreotoxic crisis]. / Plasmafiltrationsbehandlung einer thyreotoxischen Krise.

A 65-year-old man was treated three times in 4 consecutive days with plasma filtration for a severe thyroid storm. During the treatment the serum and filtrate levels of thyroxine, triiodothyronine, free T4, free T3, TBG, albumin and reverse-T3 were measured, and the results showed that, apart from reduction of the total hormone amount, the supply of binding sites for the free hormones is an important aspect in the treatment of thyroid storm.

[Endemic goiter in Austria's youth?]. / Gibt es noch eine Kropfendemie bei Osterreichs Jugend?

After 17 years the efficiency of iodine prophylaxis of endemic goiter (1 : 100000) in Austria was checked by control field studies in 3 Tyrolean towns n Austria. The data obtained there were compared with those of 123 school age children from the iodine deficient endemic goiter area of the province of Bolzano (Italy). The results show a reduction in goiter incidence from 50 to 35% in the total population in Austria, where goiter incidence in schoolchildren dropped from 45.9% to 12%. Urinary iodine/g creatinine was 65 micrograms in Austria, the 24 hr radioiodine uptake with 41.8% was normal. In comparison the ethnologically and geographically similar endemic goiter zone in the province of Bolzano showed a goiter incidence in schoolchildren of up to 46%, while urinary iodine/g creatinine was 35.9 micrograms and radioiodine uptake after 24 hr about 50%. Extensive studies of peripheral hormone parameters (T4, TBG, T3, TSH, rT3, FT3, FT4) revealed a significantly higher rT3 concentration of 24.7 ng/dl in Austria compared with a value of only 19.8 ng/dl in the province of Bolzano. These facts suggest an increased conversion of T4 to real T3 in iodine deficiency, which might contribute to the adaptation of the organism to this condition. No statement, however, can be presented regarding the regulation of this phenomenon. Even as endemic goiter is decreasing in Austria, an increase of salt iodization to 1 : 50000 according to the swiss procedure might eliminate definitely endemic goiter in Austria.

[Generalized ceroid histiocytosis in type 5 hyperlipoproteinaemia (author's transl)]. / Generalisierte Ceroidhistiozytose bei Hyperlipoproteinämie, Typ 5, nach Fredrickson.

Histochemical, fluorescence and electron microscopic features of histiocytes from the spleen, lymph nodes and liver were investigated in a patient with type 5 hyperlipoproteinaemia with splenomegaly (Fredrickson and Lees, 1965). The pigment stored in histocytes represented ceroid, a product of oxidation and polymerization of unsaturated lipids. The morphological features of ceroid and histogenesis of ceroid histiocytosis are discussed.

[Inactivation of implanted demand pacemaker through external stimulation]. / Inaktivierung des implantierten Demand-Schrittmachers durch externe Stimulation.

External chest wall stimulation was performed in 87 patients in order to overdrive and thereby suppress the implanted pacemaker. The impossibility to inactivate the implanted pacer suggested a disturbed "sensing" function in 12 patients. Marked changes of the escape rhythm were found in 77 patients with suppressable pacemaker when compared with the tracings before pacemaker implantation. Increasing degree of A-V block or marked changes in heart rate were observed in 14 of 35 cases with advanced A-V block. Minor alterations were noted in cases with sick sinus syndrome and atrial fibrillation. Overdrive suppression is a helpful method for the selection of pacemaker dependent patients.

Assessment of diagnostic value of technetium-99m pyrophosphate myocardial scintigraphy in 80 patients with possible acute myocardial infarction.

The diagnostic value of technetium-99m-pyrophosphate (Tc-pyrophosphate) myocardial scintigraphy was determined in 80 consecutive patients who had been admitted to the coronary care unit in order to rule out an acute myocardial infarction. Scintigraphic findings obtained within 5 days of admission were correlated with the final cardiac diagnosis determined for each patient. Significant myocardial uptake of Tc-pyrophosphate (positive scans) occurred in 13 of 22 patients (59%) who had enzyme and/or electrocardiographic proven acute myocardial infarct: 3 out of 5 with transmural myocardial infarct, 9 of 16 with nontransmural myocardial infarct, and 1 patient with left bundle-branch block. Of 58 patients who showed no evidence of acute myocardial infarction, positive scans occurred in 14 of 33 patients who had unstable angina pectoris (42%), 0 of 6 who had congestive heart failure, 6 of 9 who had other acute cardiac syndromes, and in 0 of 10 who had noncardiac chest pain. In the patients with unstable angina pectoris positive scans could not be predicted on the basis of the history, electrocardiographic findings or the arteriographically determined severity of the coronary artery disease. Blood levels of Tc-99m activity measured in 21 cardiac patients and in 6 volunteers did not correlate with the uptake intensity of Tc-pyrophosphate. These findings suggest caution in the use of this imaging method for the diagnosis of acute myocardial infarct in patients admitted with 'rule out myocardial infarction'.