Image-directed percutaneous biopsies with a biopsy gun

Core tissue for histologic study is believed by many pathologists to be more diagnostic than material from needle aspiration. Recently, a biopsy "gun" has been introduced, which simplifies core biopsies. With this device, 182 biopsies of multiple anatomic sites were performed with ultrasonic, computed tomographic, and fluoroscopic guidance and 18-gauge needles. High-quality histopathologic specimens were obtained in 177 of the biopsies, and diagnostic target tissue was obtained in 167. Only three significant complications occurred: one bleeding complication that required transfusion and two cases of pneumothorax that necessitated placement of chest tubes. The biopsy gun eliminated the disjointed movements of conventional "skinny" needle biopsies, and none of the samples demonstrated significant "crush" artifact or obscuring blood, problems that are commonly associated with manual biopsy techniques. Patient discomfort was decreased with this system compared with that of manual biopsies, and the total procedure time was reduced. Because of these distinct advantages, the authors now use the biopsy gun exclusively for all percutaneous biopsies and recommend that other institutions consider the use of this biopsy method.     

Cytologische und cytogenetische Untersuchungen an homologen und heterologen Lymphocyten-Mischkulturen

Zusammenfassung In Mischkulturen von menschlichen Blutlymphocyten verschiedener Spender treten auch in Abwesenheit von Phytohämagglutinin oder von spezifischen Antigenen aktivierte, blastenartige und proliferierende Zellen auf. In Erweiterung bisher vorliegender Befunde wurden Untersuchungen über die gegenseitige Lymphocytenstimulation bei der Kultivierung von Blutzellen anisogenetischer menschlicher Spender und von Milzlymphocyten der Maus und des Meerschweinchens durchgeführt. Die Ergebnisse zeigen, daß die reziproke Lymphocytenaktivierung nicht artbegrenzt ist, sondern auch in Mischkulturen der verschiedenen intra- und interspezifischen Versuchsgruppierungen vorhanden ist. Die in den homologen und heterologen Lymphocyten-Mischkulturen in wechselnder Zahl auftretenden blastenartig transformierten und proliferierenden Zellen zeigen in ihren cytologischfärberischen Eigenschaften eine weitgehende Übereinstimmung mit den unter Phytohämagglutininbzw. spezifischer Antigen-Stimulation nachweisbaren aktivierten Lymphocyten. Cytogenetische Untersuchungsverfahren erlauben mit Hilfe der Chromosomen-Marker-Technik anhand einfacher chromosomaler Erkennungsmerkmale eine Analyse der jeweiligen Herkunft der blastenartigen Zellen und liefern den Beleg dafür, daß die Lymphocyten der Spender-Partner sich gegenseitig zu stimulieren vermögen.

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Summary Blastoid transformation and proliferation of lymphocytes can be observed in mixed cultures of human white blood cells of different donors. This transformation occurs in the absence of phytohaemagglutinin or specific antigens. Observations on reciprocal activation of anisogeneic human lymphocytes of peripheral blood are supplemented by results on mixed cultures of spleen lymphocytes from the mouse and guinea-pig. It should be stressed that reciprocal lymphocytic activation is not limited to a species, but occurs in intra- and interspecific combinations from different donors. This effect can be observed in animals which show no or only a conditioned phytohaemagglutinin-response of lymphocytes. The blastoid cells occuring in homologous and heterologous mixed lymphocyte cultures display the same cytologic characteristics as the human blastoid cells induced by phytohaemagglutinin or antigenic stimulation. Cytogenetic methods provide means of identification of the individual origin of blastoid cells by using simple cytogenetic (chromosomal) markers in the different sexes or species of the donors. Thus it can be stated that mixed lymphocytic reaction leads to a mutual or two-way activation of the lymphocytes of both donors. The mixed lymphocytic reaction seems to represent a immunocytological reaction based on a membrane-bound antigen-antibody interaction of competent lymphocytes.

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Auszugsweise vorgetragen auf der 50. Tagung der Deutschen Gesellschaft für Pathologie in Heidelberg, 1966.

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Mit Unterstützung der Deutschen Forschungsgemeinschaft.     

Interleukin-1 (IL-1) production in a mouse tissue chamber model of inflammation. II. Identification of (tissue) macrophages as the IL-1 producing cells and the effect of anti-inflammatory drugs

We have used our newly described mouse tissue chamber model [1], to investigate the process of IL-1 production in more detail. The inflammatory reaction in the tissue surrounding the implanted chambers was investigated histologically and by using the polymerase chain reaction (PCR). The inflammatory response included influx of leucocytes into the granuloma surrounding the tissue chamber, expression of IL-1 on macrophages present in the inflamed tissue and an increase in the mRNA coding for IL-1 and IL-6 proteins in the granuloma. The effects of three anti-inflammatory or immunosuppressive drugs, prednisolone, indomethacin and cyclosporin A, on IL-1 and PGE₂ production in zymosan andBordetella-pertussis-vaccine (BPV)-challenged tissue chambers were also examined. Oral treatment with prednisolone and cyclosporin A of zymosan-challenged animals showed a dose-dependent reduction of IL-1 concentrations, but no effect of indomethacin. Both prednisolone and indomethacin dose-dependently reduced PGE₂ concentrations to control levels, while cyclosporin A was effective only at the highest dose tested (100 mg/kg/day p.o.). In drug-treated BPV-challenged animals, prednisolone and cyclosporin A also showed a dose-dependent reduction of IL-1, while indomethacin was again ineffective. Prednisolone and indomethacin also dose-dependently reduced the PGE₂ concentrations to control levels, whereas cyclosporin A was effective only at the highest dose tested (100 mg/kg/day p.o.).This model will be useful for investigating the mechanisms controlling the production of IL-1 from the mRNA level to the secretion of mature biologically active protein [1], and in the search for new drugs which could selectively interfere with this process.     

Biochemical assessment and clinical evaluation of a bilirubin adsorbent column (BR-350) in critically ill patients with intractable jaundice.

We investigated the efficacy of an anion-exchange adsorbent column (ASAHI BR-350, DIAMED) for removal of bilirubin and bile acids in five patients with intractable jaundice of various origin. Four litres of plasma were separated by membrane plasma separation (Plasmaflow OP-05) at a rate of 22.5 ml/min. The plasma was then perfused through an anion exchange adsorbent and returned to the venous blood line of the plasma separation. In some of the patients this procedure was combined with regular hemodialysis treatment. The concentration of total bilirubin was cut by 31 to 60%; total bile acids were reduced by 20 to 74%. Three patients recovered and had a favourable outcome. Two patients died despite the bilirubin adsorption treatment. The effects of the adsorbent column on specific blood parameters, including the coagulation system, were measured. Our data suggest that bilirubin adsorption should be examined further as a treatment for critically ill patients with intractable jaundice.     

Presynaptic short-term depression is maintained during regulation of transmitter release at a GABAergic synapse in rat hippocampus

To examine possible interactions between fast depression and modulation of inhibitory synaptic transmission in the hippocampus, we recorded from pairs of synaptically connected basket cells (BCs) and granule cells (GCs) in the dentate gyrus of rat brain slices at 34 °C. Multiple-pulse depression (MPD) was examined in trains of 5 or 10 inhibitory postsynaptic currents (IPSCs) evoked at frequencies of 10–00 Hz under several conditions that inhibit transmitter release: block of voltage-dependent Ca²⁺ channels by Cd²⁺ (10 μ m ), activation of γ-amino-butyric acid type B receptors (GABA_BRs) by baclofen (10 μ m ) and activation of muscarinic acetylcholine receptors (mAchRs) by carbachol (2 μ m ). All manipulations led to a substantial inhibition of synaptic transmission, reducing the amplitude of the first IPSC in the train (IPSC₁) by 72 %, 61 % and 29 %, respectively. However, MPD was largely preserved under these conditions (0.34 in control versus 0.31, 0.50 and 0.47 in the respective conditions at 50 Hz). Similarly, a theta burst stimulation (TBS) protocol reduced IPSC₁ by 54 %, but left MPD unchanged (0.40 in control and 0.39 during TBS). Analysis of both fractions of transmission failures and coefficients of variation (CV) of IPSC peak amplitudes suggested that MPD had a presynaptic expression site, independent of release probability. In conclusion, different types of presynaptic modulation of inhibitory synaptic transmission converge on a reduction of synaptic strength, while short-term dynamics are largely unchanged.     

The Kallikrein-Kinin system and muscle metabolism—Clinical aspects

The influence of synthetic bradykinin (BK) on disturbed protein and carbohydrate metabolism was studied in chemical and manifest maturity-onset diabetics, in surgical patients and in alloxan diabetic rats. BK,mixed with insulin and injected subcutaneously twice daily in alloxan diabetic rats lowered the morning blood glucose concentration in a dose-dependent way, whereas in a control group treated with insulin only no decrease was seen. Accelerated local blood flow or enhanced vascular permeability as a cause of increased glucose uptake could be ruled out by control experiments using papaverine and eledoisin. Better metabolic control in the BK/insulin-treated group was also indicated by lower arterial levels of free fatty acids and of -hydroxybutyrate, normalized hepatic glycogen content and better growth of body weight. In healthy man an intravenous infusion of BK (80 g/h) did not influence normal fasting blood glucose concentrations, whereas elevated glucose levels in maturity-onset diabetics were continuously reduced within 100 min by 12.2±1.4%. A comparable diabetic group receiving saline alone showed no spontaneous drop of blood glucose concentration. An improvement of pathological carbohydrate metabolism by infusion of BK i.v. could also be demonstrated using the intravenous glucose tolerance test in chemical and manifest maturity-onset diabetics and in surgical patients: in all groupsk values of the glucose tolerance test were significantly increased by BK. This effect was neither due to stimulated insulin release nor to changed glucose pool or to increased renal glucose loss, which was even reduced by BK. Interestingly, normalk values in healthy volunteers were not further improved by BK. A stimulated protein breakdown, which occurs after surgery due to peripheral insulin resistance, can also be restricted by intravenous infusion of BK: in surgical patients urinary nitrogen excretion was reduced by 50% during infusion of BK and was accelerated again after cessation of the infusion. These results indicate that BK can improve the efficacy of exogenous insulin in insulin-deficient animals and depressed insulin sensitivity in maturity-onset diabetics and surgical patients.     

Induction of rat acute-phase proteins by interleukin 6 in vivo

Recombinant human interleukin 6 (rhIL 6) was injected i.p. into male Wistar rats to investigate its role as a mediator of the acute-phase response. Hepatic mRNA levels of beta-fibrinogen, alpha 2-macroglobulin, cysteine proteinase inhibitor, alpha 1-acid glycoprotein and albumin were measured at different times after the administration of rhIL 6. Maximal increases of mRNA concentrations were observed already 4 h after the injection of rhIL 6 leading to 4.8-, 19.7-, 10- and 16-fold stimulations in mRNA levels of beta-fibrinogen, alpha 2-macroglobulin, cysteine proteinase inhibitor or alpha 1-acid glycoprotein, respectively. The rhIL 6-induced stimulation of acute-phase protein mRNA was much more rapid than the acute-phase induction after turpentine, where maximal mRNA levels were found between 16 and 24 h. For all acute-phase proteins studied, the stimulation of mRNA synthesis was found to be dependent on the dose of rhIL 6 injected. In the case of alpha 2-macroglobulin mRNA a sex-specific induction by rhIL 6 was found. Only male rats showed an acute-phase response, whereas in female rats an acute-phase reaction of alpha 2-macroglobulin mRNA was not inducible by IL 6. The increases in mRNA levels of the acute-phase proteins studied were followed by corresponding changes of the proteins in the serum determined by rocket immunoelectrophoresis. It is concluded that IL 6 represents a potent mediator of the acute-phase response in the rat.     

Cytokeratin polypeptide expression in a cloacogenic carcinoma and in the normal anal canal epithelium

Summary The aim of the present study was to explore the origin of cloacogenic carcinoma in the anal canal by immunohistochemical methods. We compared cytokeratin polypeptide expression of a cloacogenic carcinoma to normal anal epithelia, to anal squamous cell carcinoma and to basal and squamous cell carcinoma of the skin, using a battery of monoclonal anti-cytokeratin, polypeptide-specific antibodies. Our results indicate that cloacogenic carcinoma expresses cytokeratin polypeptides similar to those of the basal layer of anal squamous epithelium, of the anal transitional zone epithelium and of a layer of basal cells in the anal glands. Thus we concluded that each of the above cell types may be the cell of origin of cloacogenic carcinoma.