Comparative in vitro drug testing was performed in 72 of 183 surgically removed human colorectal cancer specimens (34 primary lesions, 38 metastases). In 10 of these tumors, comparative dose-response curves were obtained. Given a ≥70% ICF (inhibition of colony formation) as threshold for in vitro sensitivity, 5-FU was active in 16/62 specimens, and FUDR in 14/62. significantly discordant sensitivity results were observed in 8/62 tests, 5-FU being the more active agent in 5 of these cases. These data are supported by the finding of 3 considerably differing dose-response curves in 10 additional comparative studies of human primary tumors.

Die persistierende Hypercalcämie nach einer Hyperparathyreoidismusoperation stellt eine besondere Herausforderung für den Patienten und für den Chirurgen dar. Von 1/1979 bis 3/1990 haben wir insgesamt 351 Pat. an den Nebenschilddrüsen operiert, davon 34 (10%) an einer persistierenden Erkrankung. Das Durchschnittsalter betrug 62 J. Ein Drittel war asymptomatisch, bei einem weiteren Drittel lagen Nierensteine vor. In der präoperativen Lokalisationsdiagnostik wurde die korrekte Seite im CT in 34%, im US in 44% und beim selekt. Halsvenenkatheter in 63% angegeben. Insgesamt waren 44 Operationen bei den 34 Patienten durchgeführt worden, bei 24% waren bis zu 3 Explorationen erfolgt. Von den 34 Pat. haben bisher 8 die erneute Operation abgelehnt, bei 24 Patienten war der erneute Eingriff erfolgreich. Bei 8 lag eine ektope Lage vor, davon 6 im Mediastinum.

The development of a sensitive 2-site immunoradiometric assay which detects only intact human PTH (1–84) enabled us to study kinetics of PTH secretion intraoperatively. In a prospective study, we assessed the PTH (1–84) secretion mode intraoperatively in 54 patients with adenomas, in 14 patients with tertiary hyperparathyroidism (HPT), and in 2 patients with persistent HPT. After the removal of adenomatous or hyperplastic tissue, a significant drop of PTH (1–84) concentration was seen. A 50% decrease in the basal PTH concentration was reached significantly earlier for adenomas than for hyperplasias. In the 2 cases with unrevealing neck exploration, the PTH (1–84) concentrations showed hardly any change. The recovery of PTH secretion was studied in 23 patients, 20 of whom had a single adenoma; in 2 cases, a hyperplasia was present and 1 patient showed the clinical signs of a toxic HPT. We found an initial drop of PTH concentration 4 hours postoperatively below the limit of detection and a rapid recovery within 24 hours postoperatively. The PTH concentration values were well within the normal range after 48–72 hours.

In 49 patients with primary hyperparathyroidism, intact parathyroid hormone (PTH) was measured with a recently developed immunoradiometric assay, and midregional PTH fragments (sequence 44-68) were measured with an established radioimmunoassay technique. In 47 normal subjects, the concentration of intact PTH ranged from 2.0 to 6.8 pmol/l, and in 49 patients with primary hyperparathyroidism it ranged from 6.4 to 80.0 pmol/l. In contrast, midregional PTH fragments were normal in seven of 49 patients with primary hyperparathyroidism. In five healthy controls and in 12 patients with surgically confirmed primary hyperparathyroidism and serum calcium levels below 3.0 mmol/l, a rapid calcium loading test was performed. In healthy controls, intact PTH was in the low normal to subnormal range within 2.5-5.0 min, and had recovered within 15 min of calcium infusion. In patients with primary hyperparathyroidism, the calcium infusion also led to a 30-50 per cent decrease in intact PTH levels within 5.0-7.5 min after injection, with a slow recovery after 10-15 min. In six of the patients with only slightly elevated basal intact PTH, a suppression to the normal range was observed. In 24 patients (16 patients with a solitary adenoma and eight patients with four-gland hyperplasia) the intact PTH levels were followed intraoperatively during parathyroidectomy, revealing a significantly different rate of decline for single adenomas compared with hyperplasia during the first 15 min after removal of the primary enlarged gland. Intact PTH values remained constantly elevated in one patient with primary hyperparathyroidism and an unsuccessful neck exploration. These results confirm that (a) the measurement of intact PTH in patients with primary hyperparathyroidism is superior to the measurement of midregional fragments; (b) PTH secretion in primary hyperparathyroidism is not totally autonomous; and (c) intraoperative monitoring of intact PTH values could be used to monitor the success of surgery.

Persistent hypercalcemia following operation for hyperparathyroidism presents a challenge to both the patient and the surgeon. Between 1/79 and 3/90 a total of 351 patients with parathyroid disease were operated and 34 (10%) patients had persistent hyperparathyroidism. Average age was 62 years. 1/3 of pat. was asymptomatic and 1/3 had renal calculi. Preoperative studies were successful in diagnosing the affected side in 34% using CT, in 44% using sonography and in 63% when selective venous catheterization was used. A total of 44 operations were performed in 34 pat. Up to three operations were performed in 24% of patients. Eight of 34 pat. have refused additional surgery. Repeated surgery was successful in 24 pat. In eight pat. ectopic glands were identified and six of these were located in the mediastinum.

For this two-site immunochemiluminometric assay of intact human parathyrin (hPTH), the luminescent tracer was synthetic hPTH(53-84), conjugated via succinimide linkage to (aminobutyl)ethyl-isoluminol hemisuccinimide (abei-h). Purification of the labeled hPTH(53-84) by reversed-phase high-performance liquid chromatography allowed isolation of the conjugate having the highest incorporation of abei-h, 1.6 mol per mole of hPTH(53-84). The solid-phase antibody directed against the N-terminal part of hPTH was immobilized by adsorption onto the polystyrene surface of the assay tube and extracted the intact hPTH and N-terminal fragments. Another antibody against synthetic hPTH(53-84), which bound to the C-terminal part of intact hPTH, was indirectly labeled at its second free binding site with the abei-h-labeled hPTH(53-84). The assay has a detection limit of 0.5 pmol/L; it is accurate, precise, and reliable; and it shows a linear response for samples containing up to 100 pmol of hPTH per liter. The normal reference interval ranged from 1.8 to 5.9 pmol/L; 56 patients with primary hyperparathyroidism had concentrations ranging from 5.9 to 113 pmol/L. The concentrations detected in patients with idiopathic hypoparathyroidism were below the normal reference interval.

We compared the utility of measurements of serum intact human PTH-(1-84) and midregion human PTH-(44-68) in patients with disorders of extracellular calcium metabolism. Serum midregion PTH was determined by RIA, and serum intact PTH was measured by a sensitive and specific immunoradiometric two-site assay. The serum intact PTH concentrations in 70 patients with primary hyperparathyroidism were above the normal range in 69, and thus widely separated from the levels in 40 patients with hypercalcemia of malignancy, in whom serum intact PTH values were usually below normal. In contrast, both groups had overlapping serum midregion PTH values. In patients after renal transplantation and those with chronic renal failure, serum intact PTH levels were in the normal range twice as often as were serum midregion PTH values. The intact PTH assay was also superior in detecting venous gradients of the hormone and changes in PTH secretion caused by altered serum calcium concentrations, and serum intact PTH was remarkably low in hepatic venous effluent. We conclude that this new assay for serum intact PTH is superior to the midregion RIA in investigating parathyroid function in several different clinical conditions.

Mit der Entwicklung eines radioimmunometrisehen Assays zur Bestimmung von Plasmakonzentrationen des intakten menschlichen Parathormones (Sequenz 1–84) wurde eine hohe Sensitivität und Spezifität in der Diagnostik eines autonomen Hyperparathyreoidismus erreicht (1, 5). Aufgrund der Halbwertszeit des intakten Parathormons von 2 – 5 min können Plasmakonzentrationsänderungen, die in kurzen Zeitintervallen auftreten, zuverlässig ermittelt werden. In einer prospektiven Studie wurde untersucht, ob durch sequentielle Plasmaparathormonanalysen während einer Halsrevision wegen eines autonomen Hyperparathyreoidismus die Entfernung von Epithelkörperchengewebe mit einem nachweisbaren Absinken der Plasma (1–84) PTH-Konzentrationen einhergeht, und ob anhand unterschiedlicher Plasma-PTH-Konzentrationsänderungen eine Differenzierung zwischen der Erkrankung eines oder mehrerer Epithelkörperchen möglich ist.

From January to December 1985, circumcision for acquired phimosis was performed at our department in 140 boys with a median age of 4 3/4 years. The histological examination of the prepuce revealed the existence of lichen sclerosus et atrophicus (LSA) in 6 cases, e.g. 4.3% of all circumcisions performed. The striking frequency of this chronic inflammatory epithelial change and the often cited connection between the existence of LSA and the development of penile cancer during adulthood as well as the well-known tendency towards the incidence of recurrent phimosis in LSA patients support the claim for total circumcision in these cases.

In vitro colony formation and chemosensitivity were analyzed in 65 human solid tumors and compared to proliferation parameters simultaneously obtained by DNA flow cytometry of the same tumor specimens.

Prätherapeutische Tumormasse;

Based on the concept of a combined modality cancer treatment in surgical oncology, the use of the human tumour colony assay for routine chemosensitivity testing and prospective treatment planning was investigated in 204 surgical biopsies of primary human solid tumours. The majority of the tumours (135/204) were of gastro-intestinal (GI) origin. Sufficient growth for drug testing occurred in 29-67% of all tumours depending on the tumour type, with a mean of 36% in GI-carcinomas. Chemosensitivity testing in vitro against standard anti-cancer agents correlated well with clinical experience, 5-FU and FUDR being the most active drugs (27% respectively 24% sensitive tumours in vitro) in GI-carcinomas. Relatively good agreement of in vitro/in vivo correlations was seen with an overall of 25/32 correct predictions in GI and other tumours. Predictivity was particularly good for loco-regional chemotherapy. Nevertheless, the limited in vitro growth rate of gastro-intestinal tumour specimens and their chemoresistance restrict the use of this method-in particular with respect to individual treatment planning.

ABSTRACT Intravenously transplanted murine plasmacytoma MOPC‐315 cells were separated from normal spleen cells from a tumour‐bearing mouse by elutriation and characterized according to morphology, immunologic properties and clonogenicity. Morphologically, both lymphocytoid and plasmacytoid cells were separable by elutriation. Flow cytometry correlated DNA content and intracytoplasmic IgA content and demonstrated two distinct populations, both in cell cycle, but with markedly different cellular IgA levels. Density gradient separation characterized the lower‐density cells with lower IgA content and higher clonogenicity. From these studies a model of cellular differentiation is proposed.