Calcium-dependent cysteine protease activity in the sera of patients with thrombotic thrombocytopenic purpura

Plasma and serum from patients with thrombotic thrombocytopenic purpura (TTP) can cause activation and aggregation of normal human platelets in vitro. It is possible that this platelet-activating factor contributes to the disease. In this report we describe studies designed to identify the platelet-activating factor in TTP. Platelet activation by sera from 15 patients with TTP was inhibited by leupeptin, iodoacetamide, and antipain but not by phenylmethylsulphonylfluoride, epsilon-aminocaproic acid, soybean trypsin inhibitor, aprotinin, and D-phenylanyl-1-prolyl-1- arginine chloromethyl ketone. These studies suggested that the platelet- activating factor in TTP serum was a cysteine protease. We confirmed that a calcium-dependent cysteine protease (CDP) was present in the sera of each of the 15 patients when we used an assay based on the ability of CDP to proteolyse platelet membrane glycoprotein 1b (GP1b) and hence to abolish the ability of CDP-treated normal platelets to agglutinate in the presence of ristocetin and von Willebrand factor. This proteolytic activity was inhibited by EDTA, leupeptin, antipain, iodoacetamide, and by N-ethyl-maleamide (NEM) but not by the serine protease inhibitors. Activity was detected in 15 of 15 patients with TTP tested before therapy was begun. In contrast, no activity was detected in the serum of any of five of the TTP patients tested in remission or in any of the sera from 36 patients with thrombocytopenia and 423 nonthrombocytopenic controls. To look for in vivo CDP activity in patients with TTP, we studied platelets from two patients with acute TTP (drawn into acid-citrate-dextrose, NEM, and leupeptin). These platelets showed a loss of GP1b from the platelet surface. Both patients were also studied in remission: GP1b on the platelet surface had returned to normal. These studies provide evidence that CDP is present in the sera of patients with TTP, that it is specific to this disease, and that is is active in vivo as well as in vitro. We postulate that a disorder of CDP homeostasis plays a major role in the pathophysiology of TTP.     

Effects of Mild Perioperative Hypothermia on Cellular Immune Responses

Background: Unintentional perioperative hypothermia is a common complication of anesthesia and surgery associated with adverse effects on several systems, including impaired wound healing and more frequent wound infections. Mild hypothermia affects various immune functions. In the current study, the authors sought to determine whether immune alterations in the perioperative period might be induced, at least in part, by impaired thermoregulation during this period.

Methods: Sixty patients undergoing abdominal surgery were randomly assigned to two thermal care groups: routine care or forced-air warming. The patients' anesthetic care was standardized. Venous blood samples were collected 90 min before induction of anesthesia and immediately, 24 h, and 48 h after surgery. White cells were separated and frozen. Peripheral blood mononuclear cells were used to test cytokine production (interleukins [IL] -1 [small beta, Greek], -2, and -6; tumor necrosis factor-[small alpha, Greek] [TNF-[small alpha, Greek]), mitogens-induced proliferation, and natural killer NK cell cytotoxicity. Plasma cortisol levels were also determined.

Results: Patients in the normothermia group maintained normal body core temperature, whereas temperature decreased by approximately 1 [degree sign]C in the hypothermia group. Mitogenic responses were suppressed in cells from patients in the hypothermia but not in the normothermia group 24 and 48 h after surgery. Proinflammatory cytokine (IL-1 [small beta, Greek], IL-6, TNF-[small alpha, Greek]) production increased in both groups, although the production of IL-1 [small beta, Greek] was significantly higher in the normothermia group 24 h after surgery. Production of IL-2 was suppressed in the hypothermia but not in the normothermia group at 24 h.     

Wound tensile strength and contraction rate are not affected by laparotomy or pneumoperitoneum

Background: Many cellular elements responsible for wound healing are affected by laparotomy. The aim of this study was to evaluate the effects of laparotomy and CO₂ pneumoperitoneum on wound healing. Methods: Male Sprague Dawley rats were randomly assigned to one of three experimental groups. Anesthesia control rats underwent no procedure. Pneumoperitoneum group rats were insufflated with CO₂ gas. Laparotomy group rats underwent a 7-cm midline laparotomy incision. The interventions were 30 min long. For the incisional study (n= 30), a 4-cm dorsal full-thickness skin incision was made on each rat and then closed with staples. On postoperative days 7 and 14, an equal number of rats were sacrificed from each group, and wound tensile strength measurements were performed. For the excisional study (n= 45), each group of 15 rats underwent a 2-cm diameter circular dorsal full-thickness skin excision. Blinded measurements of wound area were performed every other day until wounds closed. Results: Wound tensile strength values were not significantly different among experimental groups at either time point. The study had a power of 80% to find a 30% difference at POD 7 and a power of 80% to find a 23% difference at POD 14 to a confidence level of p < 0.05. Wound contraction data from the excisional model were analyzed with the Generalized Estimation Equations statistical approach. When we modeled the treatment group as a covariate, no statistical difference was found between groups, demonstrating equal slopes across time. Conclusions: From the results of these studies, we conclude that wound healing in this model is not significantly diminished following laparotomy or peritoneal insufflation, as compared to anesthesia control. Received: 26 September 1997/Accepted: 27 January 1998     

Controlled trial of laparoscopic-assisted vs open colon resection in a porcine model

Background: Several series of laparoscopic colon resection have been reported in the literature with varied results; however, no controlled series of laparoscopic vs open colon resection has been reported. The purpose of this study was to determine the relative safety and adequacy of laparoscopic colon resection in a controlled trial using a porcine model. Methods: Domestic pigs (n=23) were randomly divided into two groups. Animals underwent either an open or laparoscopic-assisted segmental resection of the sigmoid colon. The open resections were performed through a 20-cm midline incision and the laparoscopic technique utilized five 12-mm ports. Laparoscopic resection took twice as long to complete as open resection (P<0.001). Return of gastric function was significantly faster in the laparoscopic group than in the open group (P<0.032). Results: No significant differences were found in total length of resection, proximal or distal margins, number of lymph nodes recovered, length of mesenteric vessel resected, or time to return of bowel function. At vivisection, more adhesions to the abdominal wall were noted in the open group (P<0.002). One death occurred in the laparoscopic group 2 h postoperatively (8.3% mortality) while all open group pigs survived. However, there was no statistically significant difference in mortality rates by chi-square analysis (P>0.5). Conclusions: Despite longer operative time, laparoscopic intervention is technically feasible, safe, and may offer significant postoperative benefits due to fewer abdominal adhesions.     

Entdifferenzierte chondrosarkome

Zusammenfassung Es werden der klinische Verlauf und die Resultate rontgenologischer und histologischer Untersuchungen bei 3 Patienten mit entdifferenzierten Chondrosarkomen geschildert. Die Geschwulste sind charakterisiert durch das Nebeneinandervorkommen chondrosarkomatöser Gewebsanteile von niedrigem Malignitätsgrad und fibrosarkomatöser Gewebsanteile. 1–21/2 Jahre nach Einsetzen der ersten klinischen Symptome treten Metastasen in den Lungen und in einem Fall im subcutanen Gewebe der Leistengegend auf, die das histologische Bild eines Fibrosarkoms zeigen. Eine Entdifferenzierung des Tumorgewebes bedeutet bei Chondrosarkomen regelmäßig eine erhebliche Verschlechterung der Prognose mit frühem Auftreten von Metastasen und rasch zum Tode führendem weiterem Krankheitsverlauf. Knorpelgeschwülste der axialen Skelettanteile und der großen Röhrenknochen mussen frühzeitig und radikal operativ entfernt werden, müssen frühzeitig und radikal operativ entfernt werden, insbesondere wenn sie im Röntgenbild Zeichen von proliferierendem Wachstum aufweisen.

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Dedifferentiation of chrondrosarcomas

Summary The clinical course and the results of radiographic and histological investigations in three patients with dedifferentiated chondrosarcoma are presented. The tumors were characterized by chondrosarcomatous tumor sections of low grade malignancy adjacent to fibrosarcomatous tissue sections. One to two and one-half year after the onset of the first clinical symptoms pulmonary metastases appeared and in one case a subcutaneous mass presented, which had the histological appearance of a fibrosarcoma. Dedifferentiation of a chondrosarcoma customarily has an adverse effect on the prognosis with both the early appearance of metastases and a rapidly fatal clinical course. Cartilagenous tumors of the axial skeleton and the long bones must be extirpated surgically in an early and radical fashion, particularly if there are radiographic signs of proliferation.

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Herrn Prof. Dr. E. Uehlinger zum 80. Geburtstag gewidmet     

Central nervous system high-resolution magnetic resonance imaging: effect of increasing spatial resolution on resolving power

Resolving power is a useful measure of the magnetic resonance (MR) imager-determined ability to discriminate subtle disease. Optimizing the resolving power produces the best MR images. The resolving power improves with higher spatial resolution, signal-to-noise ratio, and object contrast. Resolving power degrades with increased patient motion, which can be associated with prolonged imaging times. High and low object contrast 0.35-T MR images of the central nervous system are compared at different levels of spatial resolution and signal-to-noise ratios. In systems that have a marginal signal-to-noise ratio, the resolving power can actually decrease when higher spatial resolution is used due to further lowering of signal-to-noise ratio and to increased motion resulting from longer imaging times. This decreases the conspicuity of small, low contrast lesions.