Impact of oral ibandronate 150 mg once monthly on bone structure and density in post-menopausal osteoporosis or osteopenia derived from in vivo μCT

The effect of ibandronate 150 mg/once monthly in the treatment of post-menopausal osteopenia and osteoporosis on bone micro-structure at the distal tibia and radius has not been considered to date. Seventy post-menopausal women with osteoporosis or osteopenia were recruited. All subjects received calcium and vitamin D supplementation and were randomized to either a group which took 150 mg ibandronate oral monthly or a placebo group over a 12-month period. μCT measures of the distal tibia and radius were conducted every three months, with DXA lumbar spine and hip measurements conducted only pre and post and serum markers of bone formation and resorption measured every 6 months. After 12-months no significant impact of ibandronate on the primary outcome measures bone-volume to tissue-volume and trabecular separation at the distal tibia (p ≥ 0.15) was found. Further multiple regression analyses of the primary end-points indicated a significant effect favoring the ibandronate intervention (p = 0.045). Analysis of secondary end-points showed greater increases in distal tibia cortical thickness, cortical density and total density (p ≤ 0.043) with ibandronate and no significant effects at the distal radius, but greater increases of hip DXA-BMD and lumbar spine DXA-BMD (p ≤ 0.017). Ibandronate use resulted in a marked reduction in bone turnover (p < 0.001). While ibandronate resulted in greater mineralization of bone, this effect differed from one body region to another. There was some impact of ibandronate on bone structure (cortical thickness) at the distal tibia, but not on bone-volume to tissue-volume or trabecular separation.     

Does microcirculation play a role in the pathogenesis of inflammatory bowel diseases? Answers from intravital microscopic studies in animal models

The potential role of intestinal microcirculation for the development of inflammatory bowel diseases (IBD) has not been systematically investigated, mainly because of methodological problems. Using a well-established rodent model of IBD and intravital microscopy, the present study investigated whether (and when) gut microcirculation is disturbed in IBD, and whether microcirculatory disorders contribute to histological and functional alterations in the development of IBD. Colitis was induced by rectal injection of trinitrobenzene sulfonic acid. After 1, 3, and 15 days rats were laparotomized for intravital microscopic determination of mucosal colonic blood flow. In a second series it was examined whether enhancing colonic capillary blood flow by hemodilution therapy stabilizes colonic wall resistance and other electrophysiological parameters of gut permeability. Additional measurements involved hemodynamic monitoring and histological examinations. Colonic capillary blood flow was significantly decreased 3 days after colitis induction (1.8±0.05 vs. 2.6±0.04 nl/min in healthy control animals) when histology revealed signs of acute inflammation, and normal values after 15 days (2.4±0.06 nl/min) when chronic histological changes were evident. Hemodilution therapy enhanced colonic capillary blood flow in the initial stage (2.1±0.02 vs. 1.6±0.02 nl/min in saline-treated animals with trinitrobenzene sulfonic acid colitis) and improved gut resistance and electronic chlorid secretion (73±15 vs. 33±8 μA cm²). Histological alterations were not significantly attenuated. Impaired colonic capillary blood flow in the initial stage of experimental colitis and improved mucosal microcirculation with stabilized gut permeability suggests that the early microcirculatory disturbances precede chronic histological changes and influence functional alterations in the course of the disease. Research should be continued in this field because important mechanisms in the pathogenesis of IBD and potentially therapeutic (vasoactive) substances may otherwise be overlooked. Accepted: 23 December 1998     

Histopathologie der chronischen myeloischen Leukämie in diagnostischen Biopsien vom Knochenmark

Zusammenfassung Die Histopathologie der chronischen myeloischen Leuk?mie (CML) wird aus den diagnostischen Biopsien des Knochenmarks von 412 Philadelphia-positiven Patienten beschrieben. Besonders berücksichtigt wird die Verteilung der Megakaryozyten, die Vermehrung von Fasern, von Blasten und von speichernden Histiozyten, n?mlich der Pseudo-Gaucher-Zellen. Die Megakaryozyten waren eindeutig vermehrt bei 31,6 % der Patienten am Tag der Diagnose. Eine erkennbare Myelofibrose wiesen 15,8 % auf, eine deutliche Blastenvermehrung 2,4 % der Patienten. Speichernde Histiozyten vom Typ der Pseudo-Gaucher-Zellen zeigten 57,8 % im Knochenmark. Die Ver?nderungen werden als morphologische Kriterien der fortschreitenden Erkrankung interpretiert. Es bietet sich an, die CML semiquantitativ einzuteilen, was einfach und sicher durchgeführt werden kann. Damit wird die Erkrankung aus der Knochenmarkbiopsie heraus besser verst?ndlich und für Verlaufsuntersuchungen definiert.      

Immunohistochemical examination of routinely processed bone marrow biopsies.

Immunohistochemistry was performed on paraffin sections of 169 bone marrow biopsies fixed in a buffered methanol-formalin solution and decalcified with EDTA. The biopsies included specimens with normal hematopoiesis, and specimens that were affected by various hematological disorders as well as some metastatic carcinomas. The results demonstrate that a wide spectrum of antigens was preserved in routinely processed bone marrow biopsies, even after long-term fixation up to 12 days. Markers for granulopoietic cells were lysozyme, elastase, DAKO-M 1, and MT 1. Megakaryopoiesis was stained with glycoprotein IIIa, von Willebrand factor, and Ulex europaeus agglutinin (UEA), and erythropoiesis with LN 1. Normal lymphocytes as well as lymphoma cells of all non-Hodgkin's lymphomas tested were positive for leukocyte common antigen (LCA), and at variable degree, for MB 1, 4 KB 5, LN 1, LN 2, UCHL 1, or MT 1. Reed-Sternberg and Hodgkin's cells in Hodgkin's lymphomas were reactive with Ber-H 2, LN 2 and Dako-M 1. In plasma cell disorders, staining for immunoglobulin light chains gave best results. Metastatic carcinomas showed predominantly staining with EMA, and KL 1. A selected panel of specific cell markers is proposed, which proved to be helpful in routine bone marrow diagnosis in most cases.     

Tierexperimentelle untersuchungen zur karzinogeninduzierten tumorbildung an kolotomien in abhängigkeit von nahtmaterialien

Summary To assess the possible risk of cancer in the operated colon after stapling compared with vicryl sutures, the influence of the nickel-containing staples was tested in caecum-resected and carcinogen-treated rats. The nickel-containing staples were seen as a cocarcinogen. The aim of the study was to determine whether a higher incidence of cancer occurs at the anastomotic suture line depending on stapler vs. vicryl sutures after subcutaneous application of carcinogens (dimethylhydrazine). The results show that there is no increased risk of cancer following mechanical stapling.Herrn Prof. Dr. Dr. h.c. mult. F. Linder zum 80. Geburtstag     

Clinical aspects, diagnosis and surgical therapy of persistent primary hyperparathyroidism]

Between January 1991 and September 1991 424 patients were operated on for hyperparathyroidism (HPT) at the Department of Surgery, University of Heidelberg. In 8.5% of cases a persistent HPT was present. Our own rate of persistence was 5.4%. Ultrasound revealed the pathology in 44.2% while highly selective venous catheterization identified the correct side in 63.4%. 70% of all patients with persistent HPT required one operative revision, the remaining 30% having up to 3 revisions. 27 patients (75%) were operated on successfully. In 12 of these patients an ectopic adenoma was found. The adenoma was not identified intraoperatively in 2 patients (6.9%). One patient sustained permanent damage to the recurrent laryngeal nerve.