Warfarin-induced venous limb ischemia/gangrene complicating cancer: a novel and clinically distinct syndrome.

Venous limb gangrene (VLG) can occur in cancer patients, but the clinical picture and pathogenesis remain uncertain. We identified 10 patients with metastatic cancer (7 pathologically proven) who developed severe venous limb ischemia (phlegmasia/VLG) after initiating treatment of deep-vein thrombosis (DVT); in 8 patients, cancer was not known or suspected at presentation. The patients exhibited a novel, clinically distinct syndrome: warfarin-associated supratherapeutic international normalized ratio (INR; median, 6.5) at onset of limb ischemia, rising platelet count during heparin anticoagulation, and platelet fall after stopping heparin. Despite supratherapeutic INRs, patient plasma contained markedly elevated thrombin-antithrombin (TAT) complex levels (indicating uncontrolled thrombin generation) and protein C (PC) depletion; this profile resembles the greatly elevated TAT/PC activity ratios reported in patients with warfarin-associated VLG complicating heparin-induced thrombocytopenia. Analyses of vitamin K-dependent factors in 6 cancer patients with available serial plasma samples showed that variations in the INR corresponded most closely with changes in factor VII, with a highly collinear relationship between VII and PC. We conclude that venous limb ischemia/gangrene is explained in some cancer patients by profoundly disturbed procoagulant-anticoagulant balance, whereby warfarin fails to block cancer-associated hypercoagulability while nonetheless contributing to severe PC depletion, manifest as a characteristic supratherapeutic INR caused by parallel severe factor VII depletion.

Differential proteomics analysis of bile between gangrenous cholecystitis and chronic cholecystitis.

To establish human biliary protein expression profiles of gangrenous cholecystitis, chronic cholecystitis, and to discover differently expressed proteins for gangrenous cholecystitis by comparative proteomics, we gathered human gallbladder bile samples from gangrenous cholecystitis and chronic cholecystitis patients, respectively After removing the bile salts and lipid peptide fragments were identified by the iTRAQ-coupled LC-MS/MS technology,then identified in SwissProt with Mascot software. A total of 2251 proteins from chronic cholecystitis patients and 2180 proteins from gangrenous cholecystitis patients were identified. A total of 575 differential proteins were found between gangrenous cholecystitis and chronic cholecystitis, 159 proteins were over-expressed and 416 proteins were under-expressed in gangrenous cholecystitis. By bio-informatics analysis, in gangrenous cholecystitis, cell death, necrosis,immune response of neutrophils, apoptosis and degranulation of cells were activated; while cell survival, fatty acid metabolism, transport of molecular and proliferation of cells were inhibited, which might reflect the de-compensatory phase. Pathway analysis showed acute phase proteins were changed, indicating the role of the inflammatory response in the pathogenesis of gangrenous cholecystitis. Six acute phase proteins were found up-regulated,implying a close linkage to gangrenous gallbladder. Our study could be applicable in the biomarker discovery of gangrenous cholecystitis.

Beta-adrenergic blockade increases the hepatic extraction of glucose in sepsis.

To determine the relationship between hepatic glucose clearance and elevated epinephrine levels in sepsis, dogs with gangrenous cholecystitis were anesthetized and received either propranolol hydrochloride (mean dose, 0.29 mg/kg) or saline solution before intraduodenal glucose injection (2.5 g/kg). The amounts of glucose, insulin, and glucagon in the portal vein, the hepatic artery, and the hepatic vein were determined from the concentrations and the blood flows in these vessels over a two-hour period. Normal dogs served as controls. The amounts of glucose, insulin, and glucagon reaching the livers of both septic groups were the same. However, propranolol treatment increased the percent of glucose extracted by the liver without affecting the extractions of insulin or glucagon. Propranolol reverses the limitation of hepatic glucose extraction in sepsis by a direct effect. Whether the extracted glucose is utilizable as an energy substrate needs to be established.

Analysis of cefepime tissue penetration into human appendix.

Cefepime is a new extended-spectrum cephalosporin with gram-positive and gram-negative coverage including Staphylococcus aureus and Pseudomonas aeruginosa. We evaluated the drug's plasma, peritoneal fluid, and appendix tissue concentrations in patients with a postoperative diagnosis of perforated or gangrenous appendicitis. Patients 18 years of age or older were randomly assigned to receive either cefepime 2 g every 12 hours plus metronidazole 500 mg every 6 hours intravenously, or gentamicin 1.5 mg/kg plus clindamycin 900 mg every 8 hours intravenously. During surgery, appendix tissue, plasma, and peritoneal fluid samples were obtained, and frozen at -70 degrees C for high-pressure liquid chromatographic analysis. Thirty-five patients with perforated (26) or gangrenous (9) appendicitis had concentrations acceptable for analysis. The mean time between the administration of cefepime and the time of sampling (referred to as delta time) was 5.99 +/- 3.75 hours (mean +/- SD). The values for plasma (n = 34), tissue (n = 33), and peritoneal fluid (n = 25) concentrations were 16.27 +/- 21.87 micrograms/ml, 4.84 +/- 6.15 micrograms/g, and 14.4 +/- 22.84 micrograms/ml, respectively. The appendix tissue:plasma ratio was 0.66 +/- 0.52 and the peritoneal fluid:plasma ratio was 0.66 +/- 0.51. Spearman rank correlations indicated statistically significant correlations between plasma concentration (r = -0.889; p less than 0.0001), peritoneal fluid concentration (r = -0.783; p = 0.0002), and appendix tissue concentration (r = -0.704; p = 0.0016) versus delta time.(ABSTRACT TRUNCATED AT 250 WORDS)

Trace elements in hair of Blackfoot disease.

Blackfoot disease is a peripheral vascular disease resulting in gangrene of the lower extremities. Though extensive epidemiological study has implicated that high arsenic content in artesian well water of the endemic area bears some important connection with the disease, the etiology of the disease is still unknown. In this study, attention is paid to multielement determination in order to find out whether the trace elements in hair of Blackfoot disease patients are different from those of the controls. Experimental results indicate that the concentrations of As and Se in hair of patients are significantly higher than those of the controls, but Ca and Zn are significantly lower than those of the controls. The possible connection of these elements with the etiology of the disease is discussed.

[The detoxifying function of the pulmonary parenchyma in patients with acute infectious lung destruction]. / Detoksitsiruiushchaia funktsiia legochnoi parenkhimy u bol'nykh s ostrymi infektsionnymi destruktsiiami legkikh.

The study of arteriovenous ratio of medium-molecular oligopeptides level in 32 patients with acute infectious lung destructions has established an important detoxicating role of the lungs in endotoxemia syndrome during pulmonary-pleural suppurations. It has been found that, with the pronounced endotoxemia syndrome, during catabolic phase of the disease the lungs turn from toxin filter into their source. Detoxicating capacity of the lung parenchyma was shown to be more dependent on the severity of general metabolic disturbances than on the dissemination of suppurative lung destruction.

[Comparative morphofunctional study of the liver in peritonitis and leg gangrene]. / Sravnitel'noe morfofunktsional'noe issledovanie pecheni pri peritonite i gangrene nizhnei konechnosti.

Profound hepatic tissue morphofunctional changes with progressive hepatic failure occur in endotoxicosis caused by peritonitis and lower extremity gangrene. Comparative quantitative histoenzymatic and biochemical studies have revealed hepatic metabolic disturbances in peritonitis and leg gangrene.

Tratamiento y gestión del pie diabético / Treatment and management of diabetic foot

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Divertículo de Meckel gigante torsionado. Una presentación inusual / Giant Meckel’s diverticulum torsioned. An unnusual presentation

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A metabolic approach to the evaluation of peripheral vascular disease.

Thirty-five patients with occlusive disease of the arteries underwent metabolic studies. The arteriovenous differences of lactate, glucose and oxygen varied with the severity of the ischemic process, as assessed clinically. Lactate release and glucose extraction were significantly different from control values of patients with rest pain or with ischemic gangrene, while values in patients with claudication were comparable with those in the control group. Percutaneous muscle surface pH measurements, which reflect lactate release, decreased directly with diminished perfusion. Metabolic assessment of arterial occlusive disease may prove to be a useful clinical approach.