Generation of "neoheparin" from E. coli K5 capsular polysaccharide

Heparin remains a major drug in prevention of thromboembolic disease. Concerns related to its animal source have prompted search for heparin analogues. The anticoagulant activity of heparin depends on a specific pentasaccharide sequence that binds antithrombin. We report the generation of a product with antithrombin-binding, anticoagulant, and antithrombotic properties similar to those of heparin, through combined chemical and enzymatic modification of a bacterial (E. coli K5) polysaccharide. The process is readily applicable to large-scale production.     

Prevalence and determinants of left ventricular hypertrophy in acromegaly: impact of different methods of indexing left ventricular mass

BACKGROUND: Left ventricular hypertrophy (LVH) is the most common cardiac abnormality in acromegaly. Left ventricular mass (LVM) is an important parameter measured to detect LVH, but the relationship with body size should be considered by correcting LVM to body surface area (BSA), height or height2.7. All trials concerning acromegaly have detected LVH on the basis of LVM indexed for BSA, but have been criticized for disregarding the effects of obesity. PATIENTS AND MEASUREMENTS: 97 patients with active acromegaly and a control group of 97 nonacromegalic subjects, were compared for the prevalence of LVH, calculated with different corrections of LVM for BSA, height and height2.7. In addition, we evaluated determinants of LVH in acromegalic group. RESULTS: In controls, the prevalence of LVH, determined by correcting LVM for BSA (10.3%) was significantly lower than correcting by LVM/height (21.6%, P = 0.05) and LVM/height2.7 (33%, P < 0.0001). Similarly, in the acromegalic population the prevalence of LVH was significantly higher when measured by LVM/height (86.6%) or LVM/height2.7 (89.7%), than by LVM/BSA (67%) (P = 0.002 and P < 0.0001, respectively). A lower prevalence of LVH detected by LVM/BSA than LVM/height and LVM/height2.7 has been observed in an acromegalic overweight group, while in patients with normal weight there was no significant differences using different corrections. In acromegalic patients with disease duration of 10 years. By separate multiple regression analyses systolic blood pressure was the only independent determinant of LVM/BSA or LVM/height, while systolic blood pressure and GH levels were both predictors of LVM/height2.7. CONCLUSIONS: LVM indexed for height2.7 appears to be the most appropriate method to identify LVH in acromegaly, particularly in overweight patients and those with shorter disease duration.     

Decrease of serum carnitine levels in patients with or without gastrointestinal cancer cachexia

AIM: To evaluate the levels of serum carnitine in patients with cancer in digestive organs and to compare them with other cancers in order to provide new insights into the mechanisms of cachexia. METHODS: Fifthy-flve cachectic patients with or without gastrointestinal cancer were enrolled in the present study. They underwent routine laboratory investigations, including examination of the levels of various forms of carnitine present in serum (i.e., long-chain acylcarnitine, short-chain acylcarnitine, free carnitine, and total carnitine). These values were compared with those found in 60 cancer patients in good nutritional status as well as with those of 30 healthy control subjects. RESULTS: When the cachectic patients with gastrointestinal cancer were compared with the cachectic patients without gastrointestinal cancer, the difference was -6.8μmol/L in free carnitine (P < 0.005), 0.04μmol/ L in long chain acylcarnitine (P < 0.05), 8.7μmol/L in total carnitine (P < 0.001). In the cachectic patients with or without gastrointestinal cancer, the difference was 12.2μmol/L in free carnitine (P < 0.001), 4.60μmol/L in short chain acylcarnitine (P < 0.001), and 0.60μmol/L in long-chain acylcarnitine (P < 0.005) and 17.4μmol/L in total carnitine (P < 0.001). In the cachectic patients with gastrointestinal cancer and the healthy control subjects, the difference was 15.5μmol/L in free carnitine (P < 0.001), 5.2μmol/L in short-chain acylcarnitine (P < 0.001), 1.0 umol/L in long chain acylcarnitine (P < 0.001), and 21.8 umol/L in total carnitine (P < 0.001). CONCLUSION: Low serum levels of carnitine in terminal neoplastic patients are decreased greatly due to the decreased dietary intake and impaired endogenous synthesis of this substance. These low serum carnitine levels also contribute to the progression of cachexia in cancer patients.     

Major elective surgery for vascular disease in patients aged 80 or more: perioperative (30-day) outcomes

Although major vascular surgery is performed with increasing frequency in elderly people, the impact of age on outcomes is uncertain. We evaluated the perioperative (30-day) outcomes for patients who underwent major elective vascular operations under general or peripheral anesthesia in their eighties and nineties in a 14-year period. Data for all consecutive 3,060 patients (456 of them > or years old) who underwent 3,314 elective vascular surgery procedures were prospectively entered into a computerized vascular registry. Detailed information was collected on patients' preoperative status, type of procedure and anesthesia, perioperative outcomes, and predictors of perioperative outcomes. The end points of the study were perioperative death and main surgical complications. Perioperative all-cause mortality rates varied across operations and were higher in elderly than in younger patients (1.4% vs. 0.2%, P = 0.014) after abdominal surgery (2.4% vs. 0.1%, P = 0.006) and especially after abdominal aortic aneurysm repair (2.8% vs. 0%, P = 0.035). In the elderly cohort, the mortality rate was <1% for almost 60% of all operations. In logistic regression analysis, only preoperative hypertension (odds ratio [OR] = 72.5, 95% confidence interval [CI] 9.4-557.6), congestive heart failure (OR = 16.5, 95% CI 2.3-115.9), and perioperative cardiac (OR = 20.7, 95% CI 1.6-273.8) and pulmonary (OR = 41.7, 95% CI 7.9-218.9) complications were associated with a higher 30-day death risk. In this series, perioperative outcomes were not influenced by the type of elective surgical procedure. Though overall mortality after major vascular surgery was higher in patients > or 80 years old, age per se was not an independent factor of a higher perioperative mortality risk or fatal and nonfatal complications.