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Localized Castleman's disease presenting as a vascular right iliac fossa mass.

Castleman's disease is a rare lymphoproliferative disorder of unknown aetiology. The presentation is varied, diagnosis is difficult, and optimum management is still unknown. We report our experience with a case of Castleman's disease in a 34-year old woman who presented with pallor, hepatosplenomegaly, and a right iliac fossa mass that was 5 cm in diameter. this was initially diagnosed as a soft tissue sarcoma and preoperative tumour embolization was planned before excision. Mesenteric arteriogram revealed that the feeder arteries arose from the superior mesenteric artery and embolization was aborted for fear of causing bowel ischaemia. On laparotomy, lymphoid enlargement was found between the leaves of the jejunal mesentery. The tumour was relatively avascular and the overlying mesenteric vessels contributed to teh duplex ultrasound and computerized tomography appearance of hypervascularity. The tumour with the mesentery and the overlying segment of jejunum was excised completely. Histopathology confirmed Castleman's disease. The purpose of this report is to present this rare case that caused a diagnostic dilemma and to review the management of this disorder.

Adult↗

Clinically applicable thermal preconditioning attenuates leukocyte-endothelial interactions.

BACKGROUND: We have previously demonstrated that clinically applicable thermal preconditioning induces heat shock protein 72 (HSP72) and protects against a subsequent ischemia-reperfusion (I/R) injury in an animal model. A core component of I/R injuries is the interaction between activated leukocytes and endothelial cells. We hypothesized that the effects of clinically applicable thermal preconditioning are mediated through attenuation of this leukocyte-endothelial (L-E) interaction. STUDY DESIGN: Twenty-one male Sprague Dawley rats were divided into control, I/R, and preconditioning plus I/R groups. Preconditioning was done under general anesthesia and the animals' temperature raised by 1 degrees C for 15 minutes in a water bath. This was repeated once a day for 5 successive days. I/R injury was caused by occlusion of the superior mesenteric artery for 10 minutes followed by 1 hour of reperfusion. L-E interactions were analyzed using intravital microscopy of a mesenteric vessel in vivo. L-E interactions were determined using leukocyte velocity (which decreases as cells interact), and number of adherent and migrated leukocytes. HSP72 was assessed by Western blot. RESULTS: Ischemia-reperfusion caused a decrease in leukocyte rolling velocity at all timepoints (p < 0.05 versus controls). Preconditioning attenuated the effects of I/R, and leukocyte rolling velocity was significantly improved versus I/R (p < 0.05) to levels similar to those in controls. Similarly, the number of adherent and migrating leukocytes increased significantly (p < 0.05) after I/R versus control at all time points, and preconditioning attenuated these to control levels, (p < 0.05 versus I/R) at both the 30- and 60-minute postischemia time points. Upregulation of HSP72 was demonstrated on Western blot. CONCLUSIONS: These results demonstrate that the benefit of clinically applicable thermal preconditioning is at least partially because of an immunomodulatory role in attenuating leukocyte-endothelial interactions associated with an increased expression of HSP 72.

Analysis of Variance↗

6-Chloro-3-alkylamino-4H-thieno[3,2-e]-1,2,4-thiadiazine 1,1-dioxide derivatives potently and selectively activate ATP sensitive potassium channels of pancreatic beta-cells.

6-Chloro-3-alkylamino-4H-thieno[3,2-e]-1,2,4-thiadiazine 1,1-dioxide derivatives were synthesized and characterized as activators of adenosine 5'-triphosphate (ATP) sensitive potassium (K(ATP)) channels in the beta-cells by measuring effects on membrane potential and insulin release in vitro. The effects on vascular tissue in vitro were measured on rat aorta and small mesenteric vessels. Selected compounds were characterized as competitive inhibitors of [(3)H]glibenclamide binding to membranes of HEK293 cells expressing human SUR1/Kir6.2 and as potent inhibitors of insulin release in isolated rat islets. 6-Chloro-3-(1-methylcyclobutyl)amino-4H-thieno[3,2-e]-1,2,4-thiadiazine 1,1-dioxide (54) was found to bind and activate the SUR1/Kir6.2 K(ATP) channels in the low nanomolar range and to be at least 1000 times more potent than the reference compound diazoxide with respect to inhibition of insulin release from rat islets. Several compounds, e.g., 3-propylamino- (30), 3-isopropylamino- (34), 3-(S)-sec-butylamino- (37), and 3-(1-methylcyclopropyl)amino-4H-thieno[3,2-e]-1,2,4-thiadiazine 1,1-dioxide (53), which were found to be potent and beta-cell selective activators of K(ATP) channels in vitro, were found to inhibit insulin secretion in rats with minimal effects on blood pressure and to exhibit good oral pharmacokinetic properties.

ATP-Binding Cassette Transporters↗

Glyprolines and semax prevent stress-induced microcirculatory disturbances in the mesentery.

One-hour immobilization stress considerably disturbed microcirculation in the mesentery: blood flow in small mesenteric vessels decreased or stopped and numerous hemorrhages appeared. Lymphatic vessels lost spontaneous activity and did not respond to norepinephrine. Administration of Semax and glyprolines 1 h before stress decreased the severity of stress-induced microcirculatory disturbances. PGP and GP were most effective in this respect.

Adrenocorticotropic Hormone↗

Complexities in ETS-domain transcription factor function and regulation: lessons from the TCF (ternary complex factor) subfamily. The Colworth Medal Lecture.

The ETS-domain transcription factor family can be divided into a series of subfamilies. Elk-1 represents the founding member of the ternary complex factor (TCF) subfamily. By focusing on the TCF subfamily, we can demonstrate the complexities that exist in the function and regulation of ETS-domain transcription factors. This article focuses on Elk-1 in detail and summarizes the functions of other TCFs. The key themes covered include the domain structure of the TCFs, the mechanisms of complex formation with serum response factor, regulation of TCFs by mitogen-activated protein kinase cascades, and transcriptional regulatory properties of the TCFs. Finally, the emerging role of the TCFs in vivo is discussed. A picture is developing indicating that, while these proteins exhibit significant sequence and functional conservation, key differences in their structure and regulation are being identified which may relate to unique functions of these proteins in vivo.

Amino Acid Sequence↗

The role of noradrenaline and other transmitter hormones in the pathogenesis of hypertension.

1. Studies with a sensitive radioenzymatic assay for plasma noradrenaline suggest there is a selective overactivity of the sympathetic nerous system in essential hypertension. 2. Serotonin turnover in the mesenteric vessels is approximately twice that of noradrenaline and it is suggested that serotonin may interact with noradrenaline to maintain vascular resistance. 3. Methodology which allows the study of local sympathetic turnover in nuclei of the central nerous system and in peripheral blood vessels is decribed. This approach has been used to study non-innervated sympathetic turnover observed in phaceochromocytoma.

Adrenal Gland Neoplasms↗

Low dose indapamide plus perindopril combination effects on cardiovascular structure and function in genetic hypertension.

1. Although the fixed combination preparations of thiazide and angiotensin-converting enzyme inhibitor are gaining wide acceptance in clinical practice, data on the basic pharmacology of the combinations are relatively limited. The long-term structural and functional effects of a fixed low dose (0.24 + 0.76 mg/kg per day) combination of indapamide + perindopril (I + P,S5590) is spontaneously hypertensive rats (SHR) were examined in the present study. 2. Male SHR (10-12 weeks) were treated with I + P or vehicle for 8 weeks. The blood pressure and heart rate were monitored by weekly measurements. At the end of the treatment period, left ventricular, aortic and intramyocardial coronary arteriole structures were assessed. Contractile and relaxant properties of mesenteric arteries were determined by wire-myography. 3. Indapamide + perindopril combination caused a significant lowering of both systolic (P < 0.001) and diastolic (P < 0.001) blood pressures. Left ventricle plus septum:bodyweight ratio (P < 0.001), aortic medial cross-sectional area (P < 0.05) and media:lumen ratios (P < 0.005) were all significantly reduced by I + P treatment. In contrast, the effect of I + P on intramyocardial coronary vascular structure did not reach statistical significance. There was some improvement in endothelium-independent vasorelaxation of mesenteric vessels but contractile responses to noradrenaline and calcium were unaffected by treatment. 4. In summary, a low dose I + P combination treatment of SHR partly normalizes both systolic and diastolic blood pressures. Cardiac and larger vessel hypertrophy was reversed but intramyocardial coronary arteriole structure was not as readily regressed by the end of the study.

Animals↗

Rectal cancer and ulcerative colitis: does it change the therapeutic approach?

OBJECTIVE: The aim of this study was to examine the incidence of coexisting colorectal cancer in ulcerative colitis in a population of patients undergoing ileal pouch anal anastomosis. The frequency of rectal cancer in this population, surgical intervention, general outcomes and cancer recurrence are described. METHODS: Data on 1850 patients undergoing restorative proctocolectomy from 1983 to 2001 were reviewed. Information was gathered from data in the department's pelvic pouch database, as well as pathology and surgical reports. Follow-up questionnaires routinely sent to patients as part of the database were included in the analysis to determine current functional status. Mean follow-up period was 7.5 years after surgery. RESULTS: Seventy patients had coexisting colorectal cancer at time of IPAA. 7 (10%) of cancers were incidental. Pre-operative duration of disease was 18.6 years. Twenty-six of the cancers were rectal cancers. The most common form of anastomosis in the rectal cancers was mucosectomy, especially in pre-operatively known rectal cancer or low lying dysplasia. Preferred surgical technique for rectal cancer in mucosal ulcerative colitis (UC) included high ligation of mesenteric vessels with radical colectomy and taped occlusion of the rectum with irrigation of the rectal stump with Turnbull solution prior to mucosectomy. Patients with Stage 3 cancers received postoperative chemotherapy. Post-operative radiation therapy was not commonly recommended. Five of 70 patients were deceased from metastatic colon cancer; 55 patients were confirmed alive with good to excellent pouch function with a follow-up range of 1-17 years. CONCLUSION: Restorative proctocolectomy with ileal pouch anal anastomosis is a successful surgical approach for patients with coexisting colorectal cancer in UC. When the appropriate surgical technique is used in patients with colon or rectal cancer, along with adjuvant chemotherapy when appropriate, prognosis and function is very good.

Anastomosis, Surgical↗

Natural history of experimental intestinal atresia: morphologic and ultrastructural study.

PURPOSE: The aim of this study was to evaluate a natural history of congenital intestinal atresia (IA) in the chick embryo and to assess the type and nature of changes in the intestine at various developmental stages. METHODS: Chick embryos underwent operative induction of IA on the 12th day of incubation. The procedure consisted of electrocoagulation of the mesenteric vessels supplying a 7- to 8-mm intestinal segment. The embryos were subjected to macroscopic examination, histologic and ultrastructural studies of the preatretic and postatretic bowel using the light microscope, scanning, and transmission electron microscopes. All investigations were performed in an experimental group (operated embryos), in a control group, and in a sham-operated group on the 15th, 17th, 19th, and 21st day of incubation. RESULTS: The original technique of an iatrogenic "vascular event" proved to be effective because IA developed in 96% of embryos surviving the procedure. The affected portion of the bowel underwent progressive necrosis, and signs of bowel obstruction could be observed 48 hours after operation. Cord atresia (type II) developed in 81% of embryos. Histologic investigations showed progressive thinning of mucosa, flattening of mucosal folds, and epithelial detachment within the intestine proximal to atresia. There was only mild hypertrophy of the muscular layers. All these pathomorphologic changes were of rapidly progressive nature until the 17th day of incubation. Later, the rate of distension of preatretic bowel and histologic changes were less. Ultrastructural investigation of the proximal bowel showed progressive flattening of the enterocytes associated with their apical bulging, widening of the intercellular spaces, and microvilli atrophy. Surprisingly, at days 19 and 21 of incubation, signs of induction of adaptive mechanisms with partial restoration of near-normal microvilli pattern were observed. CONCLUSIONS: Study of natural history of experimental IA indicates that histologic and ultrastructural lesions of the bowel are of dynamic nature and are not only the effect of pathologic intraluminal pressure.

Animals↗

[Early abdominal manifestation of neurofibromatosis type ! in a 12-year-old boy]].

Neurofibromatosis type 1 (NF 1) is a neuroectodermal tumor in which abdominal manifestations occur in about 25% of cases in addition to the typical cutaneous lesions. A child with a severe form of an abdominal manifestation of NF 1 was treated in the Hanover Medical School by tumorresection. Pre-operative diagnosis using CT, angiography and ultrasound showed an enormous abdominal tumor constricting the mesenteric vessels. The tumor and the affected portion of the small intestine (150 cms) were removed surgically. No tumor recurrence was observed nine months after operation. Surgical removal is the only currently available therapy for treating tumors of this size.

Child↗

Experimental intestinal obstruction in rats. Studies on structure and disaccharidase activities.

An experimental model of congenital intestinal obstruction (CIO) was created in rats by means of fetal intrauterine surgery between the 16th and 20th days of gestation. By the use of a microsurgical technique areas at the mid-jejunum or the jejuno-ileal junction were infarcted by coagulation of mesenteric vessels. Gestation was terminated by Cesarean section within 24 hours before expected term to avoid cannibalism. The structure of the intestinal mucosal cells proximal and distal to the CIO at the light microscopy as well as the ultrastructure level was not changed indicating that the surgical method was successful. The activities of the brush border enzymes, maltase and lactase were significantly reduced distal to the obstruction as compared to controls. Proximal to the obstruction lactase was the only enzyme showing reduced activity in comparison to controls. These findings were not dependent on the localization of the obstruction or when it was performed and suggest that CIO causes selective changes of the biochemical properties of the cell membrane. The results are in agreement with the findings of disaccharidase activities in biopsies taken from human infants with CIO and point to the importance of a normal intestinal passage for the development of brush border enzymes.

Animals↗

Anatomical variations of the arterial pattern in the right hemiliver.

The arterial supply to the right hemiliver was studied in 80 liver casts. The arteries were divided into 10 groups according to their origin and branching pattern. The right hemiliver was supplied by one artery in 96% of cases and by two arteries in 4%. When there was only one artery it originated from the proper hepatic artery in 73/77 cases and from the superior mesenteric artery in 4/77 cases. The replacing right hepatic artery which originated from the superior mesenteric vessel supplied the whole right hemiliver in 5% of cases. The incomplete replacing right hepatic artery which supplied only a part of the right hemiliver was found in 4% of cases. The anterior section (segments 5 and 8) was supplied by one artery in 61%, by two arteries in 30% and by three arteries in 9% of cases. The posterior section (segments 6 and 7) was supplied by one artery in 66%, by two arteries in 31% and by three arteries in 3% of cases. Segments 5 and 7 were predominantly supplied by one artery, whereas segments 6 and 8 by two arteries.

Autopsy↗

Blunt pancreatic trauma. Role of CT.

PURPOSE: To define the evolution patterns of blunt pancreatic trauma, and to point out the CT features most significant for the diagnosis. MATERIAL AND METHODS: Ten cases of pancreatic trauma, observed over a period of about 10 years, were analyzed in retrospect. The cases were divided into 3 groups according to the time that had elapsed between trauma and first CT: early phase (within 72 h: n=3/10); late phase (after 10 days: n=3/10); and following pancreatic drainage (n=4/10). RESULTS: In the early phase, one case showed a blood collection surrounding the pancreatic head and duodenum, and displacing the mesenteric vessels to the left. In the 2 other cases it was possible to demonstrate a tear in the pancreas at the neck, perpendicular to the main pancreatic axis. In the late phase in all 3 cases, one cystic lesion was present at the site of the tear, either surrounding the gland or embedded - more or less deeply - within the parenchyma. One of the lesions subsided spontaneously; the 2 others required surgery. In the postoperative phase, an external fistula was demonstrated in 2 cases following percutaneous drainage of pancreatic cysts; the fistula was fed by a cystic lesion in the pancreatic neck. In the 2 other cases a pseudocyst developed. CONCLUSION: Early demonstration of a parenchymal tear was difficult. At a later stage the diagnosis was easier owing to the demonstration of cystic lesions within the parenchyma at the site of the tear. The surgical drainage of this lesion does not usually lead to healing since an external fistula or a pseudocyst may develop.

Adult↗

Analysis of the correlation of plasma NO and ET-1 levels in rats with acute mesenteric ischemia.

Mesenteric ischemia is a devastating disease process that frequently challenges clinicians. To enhance the early diagnosis of gut ischemia and judgment of its severity, it may be helpful to detect the unusual existence or increase in biomarkers in the body fluid. The aim of the present study was to evaluate the correlation of plasma nitric oxide (NO) and endothelin-1 (ET-1) levels to mesenteric ischemia using an animal model. Acute mesenteric ischemia (AMI) was produced experimentally by occlusion of the mesenteric vessels in the terminal ileum by the tenting of a thread. The determination of plasma NO and ET-1 levels were obtained before operation (T0, baseline value), and at 10 (T10), 20 (T20), 30 (T30), and 60 (T60) min after the creation of AMI. Sham-operated rats served as controls. After 30 min of experiments, the plasma NO and ET-1 levels were significantly higher in the AMI group than in the control group (both p < .01). Both the plasma NO and ET-1 levels in AMI group increased significantly after 30 min of ischemia (both p < .001 vs. respective baseline value), and they were 60% and 84% above the baseline value, respectively. In addition, ischemic intestinal injury was confirmed by the significantly elevated histological scores in the AMI group after 60 min of ischemia (p < .001). Our preliminary results suggest the possibility of important insights regarding NO and ET-1 changes into the mechanism of pathogenesis in AMI in rats. The increases in plasma NO and ET-1 levels may potentially be noninvasive biomarkers for the early detection of this disease.

Acute Disease↗

Retroarterial colon with right-sided obstructive gangrenous colitis.

Retroarterial colon is a rare entity in which the colon is located behind the superior mesenteric vessels. Transmesenteric internal hernias result in portions of the bowel protruding through a defect in the mesentery and are often acquired but may be congenital. We report a 10-year-old female with trisomy 13 who lacked retroperitoneal fixation of the intestines and had a retroarterial transverse colon possibly resulting from a congenital transmesenteric internal hernia, that eventually lead to obstructive gangrenous colitis.

Abnormalities, Multiple↗

Studies on solute transfer in the vascular endothelium.

Barium chromate, Prussian blue, and cobalt-cobalticyanide can be precipitated in vivo in the endothelium of mesenteric vessels by injection of the appropriate anions into the blood stream, and topical application of the precipitating cations to the exposed mesenteries of mice and frogs. Precipitation in the endothelium occurs in the form of a diffuse fine punctate precipitate, and also as continuous lines demarcating endothelial cell outlines. A striking feature is the frequent occurrence of this type of precipitation in a tapering zone downstream from mural thrombi in the veins.

Animals↗

PRODUCTION OF INFLAMMATORY CHANGES IN THE MICROCIRCULATION BY CATIONIC PROTEINS EXTRACTED FROM LYSOSOMES.

Lysosomal granules of rabbit exudate polymorphonuclear (PMN) leucocytes were isolated and then lysed by freezing-thawing. Topical application of this material to rat and rabbit mesentery produced sticking and emigration of leucocytes, stasis of blood flow, and petechial hemorrhage. The granule-free, supernatant fraction of the homogenized leucocytes failed to produce any of these reactions. Cationic proteins extracted from these granules by weak acid and precipitated by ethanol at concentrations of 20 and 45 per cent, were also tested on heterologous, homologous, and autologous mesenteric vessels. The 20 per cent ethanol-precipitated fraction produced all of the aforementioned injury reactions, whereas the 45 per cent fraction was inactive. The intensity of inflammatory changes produced by the active cationic protein fraction was greater than that produced by lysed whole granules. Both the 20 per cent and 45 per cent ethanol fractions of cationic protein induced clumping of rabbit platelets, in vitro. The 20 per cent ethanol fraction also caused a slight acceleration in rate of swelling of isolated rabbit liver mitochondria. The active material proved to be non-pyrogenic in rabbits. This material exhibited no kinin-like effects when tested on isolated smooth muscle preparations (rabbit aorta and guinea pig ileum). In the rat, the protein produced a transient vasodepression which was inhibited by pretreatment of the animal with an antihistamine. Ultraviolet absorption data and ribose assays showed that the 20 per cent ethanol fraction contained only 4 per cent or less of ribonucleic acid. Upon electrophoresis in starch gel, using acid buffer, this fraction separated into at least three major components which migrated towards the cathode. Precipitation of one of the slowly migrating components by titration of the fraction to pH 10.5 greatly increased the inflammatory activity of the material. The inflammatory basic protein fraction was essentially devoid of acid phosphatase, beta glucuronidase, acid ribonuclease, lysozyme, and catalase activity. The non-inflammatory basic protein fraction contained appreciable quantities of acid ribonuclease and lysozyme. The foregoing data demonstrate that certain of the cationic proteins present in lysosomes of rabbit exudate PMN leucocytes can reproduce one of the cardinal features of the inflammatory response; namely, adhesion and emigration of leucocytes in the microcirculation. These findings offer fresh support for the role of lysosomes in the pathogenesis of tissue injury, and may help to account for the propagation of leucocyte emigration to peak numbers during inflammatory reactions.

Acid Phosphatase↗

Alteration of the response of platelets to surface stimuli by pyrazole compounds.

Sulfinpyrazone and phenylbutazone block the aggregating action of collagen, antigen-antibody complexes, and gamma globulin-coated surfaces on blood platelets. These drugs do not block the action of ADP or thrombin. Inhibition of surface-induced aggregation appears to be the result of a decreased response of the platelets to surface stimuli, giving rise to diminished release of platelet constituents, such as ADP and serotonin. The intravenous infusion of these drugs produced results similar to those found in the in vitro experiments. Administration of phenylbutazone in doses sufficient to produce marked suppression of the platelet-collagen reaction impaired hemostatic plug formation at the ends of transected mesenteric vessels in rabbits. Since platelet function is considered a factor influencing platelet survival, the effect of phenylbutazone on platelet survival was examined. It was found that phenylbutazone prolonged platelet survival to more than twice the normal time and reduced platelet turnover by nearly 50%. These studies show that drugs which suppress platelet response to surface stimuli alter platelet function in vivo.

Adenine Nucleotides↗