The impact of supplemental n-3 long chain polyunsaturated fatty acids and dietary antioxidants on physical performance in postmenopausal women.

OBJECTIVES: Identify relationships and evaluate effects of long chain polyunsaturated fatty acids (LCPUFA) on frailty and physical performance. DESIGN: Randomized, double blind pilot study. SETTING: University General Clinical Research Center. PARTICIPANTS: 126 postmenopausal women. INTERVENTION: 2 fish oil (1.2g eicosapentaenoic acid [EPA] and docosahexaenoic acid [DHA]) or 2 placebo (olive oil) capsules per day for 6 months. All participants received calcium and vitamin D supplements. MEASUREMENTS: Fatty acid levels, frailty assessment, hand grip strength, 8 foot walk, body composition, medical history and co-morbidities, nutrient intake, and inflammatory biomarkers taken at baseline and 6 months. RESULTS: At baseline, those with greater red blood cell (RBC) DHA and DHA/arachidonic acid (AA) presented with less frailty (r = -0.242, p=0.007 and r = -0.254, p=0.004, respectively). Fish oil supplementation resulted in higher RBC DHA and lower AA compared to baseline and placebo (p<0.001) and an improvement in walking speed compared to placebo (3.0±16 vs. -3.5±14, p=0.038). A linear regression model included age, antioxidant intake (selenium and vitamin C), osteoarthritis, frailty phenotype, and tumor necrosis factor alpha (TNFα). The model explained 13.6% of the variance in the change in walking speed. Change in DHA/AA (p=0.01) and TNFα (p=0.039), and selenium intake (p=0.031) had the greatest contribution to change in walking speed. CONCLUSION: Physical performance, measured by change in walking speed, was significantly affected by fish oil supplementation. Dietary intake of antioxidants (selenium and vitamin C) and changes in TNFα also contributed to change in walking speed suggesting LCPUFA may interact with antioxidants and inflammatory response to impact physical performance.

Variability in results of the microscopic agglutination test in dogs with clinical leptospirosis and dogs vaccinated against leptospirosis.

BACKGROUND: The microscopic agglutination test (MAT) is commonly used for the diagnosis of canine leptospirosis. In dogs it is sometimes suggested that the serogroup with the highest MAT titer is the infecting serogroup; however, this is not true in humans with confirmed leptospirosis. We sought to investigate the value of MAT results in predicting the infecting serogroup by comparing results across several laboratories and within individual dogs over time. OBJECTIVES: To examine the variability in MAT results across different laboratories in dogs recently vaccinated against leptospirosis, and in dogs with clinical leptospirosis, and to investigate variability over time in MAT results in individual dogs with leptospirosis. ANIMALS: Eighteen dogs from a research colony, 9 of which had been vaccinated against leptospirosis, and 17 dogs clinically diagnosed with leptospirosis. METHODS: Serum samples were submitted to up to 5 veterinary diagnostic laboratories for MAT titers from each dog on at least 1 occasion. MAT results also were followed over time in 6 dogs diagnosed with leptospirosis. RESULTS: MAT results were discordant across different laboratories in dogs recently vaccinated against leptospirosis and in dogs with clinical leptospirosis. MAT results varied over time in individual dogs with the disease. CONCLUSIONS AND CLINICAL IMPORTANCE: The MAT is a valuable test for the diagnosis of leptospirosis in dogs, but it is unlikely that test results can be used to predict the infecting serogroup. Laboratories offering the MAT should consider participation in a proficiency scheme.

Postpyloric enteral feeding costs for patients with severe head injury: blind placement, endoscopy, and PEG/J versus TPN.

This study describes the advantages and disadvantages of several forms of enteral nutrition for patients with severe head injury (Glasgow Coma Scale Score [GCS], <12). Included in the study are nasoenteric nutrition delivery using blind, endoscopic, percutaneous endoscopic gastrostomy (PEG) and PEG with jejeunostomy (PEG/J), and open jejeunostomy tube placement methods. These methods are compared with parenteral delivery of nutrition. The study constituted a retrospective analysis of the success rate of early enteral feedings by blind, endoscopic PEG and PEG/J and by open jejeunostomy placement of small-bowel feeding tubes for 57 patients with severe head injury. The delivery cost of enteral nutrition per intensive care unit day was compared to the delivery cost of parenteral nutrition per intensive care unit day in the same group of patients. Fifty-three percent of patients were adequately maintained nutritionally with nasoenteric delivery alone and did not require parenteral feeding. The average number of days for initiation of either enteral or parenteral feedings was 1.8 +/- 0.2 days from injury [standard error of mean (SEM); range, 0-10 days]. An average of 3.3 days (range, 0-23 days) was required for feeding tube placement in all patients. For 70% of patients, tube placement was completed within 48 h after injury. Full-strength, full-rate enteral feedings were achieved by a mean of 4.9 days after injury. A total of 128 feeding tubes were placed while the patients were in the intensive care unit (ICU; 2.2 +/- 0.2 tubes per patient). Blind placement of feeding tubes into the small bowel was rarely achieved without repositioning. Endoscopic tube placement into the duodenum was achieved in 50% of patients, into the jejunum for 33% of patients, and into the stomach for 18% of patients. While in the intensive care unit, patients received an average of 77 +/- 2% of their measured energy expenditure (range, 57-114%). Eleven percent of patients experienced severe gastrointestinal problems. Other problems were associated with the inability to achieve or maintain access: dislodged tubes (30%), clogged or kinked tubes (21%), and mechanical access problems (7 %). Seventy-one percent of patients in barbiturate coma were able to tolerate early nasoenteric feedings. Aspiration pneumonitis occurred equally among patients fed nasogastrically and those fed nasoenterically. The overall aspiration rate was 14%. The cost of acute enteral feeding was $170 per day and that for parenteral feeding, $308 per day. We conclude that blind transpyloric feeding tube placement is difficult to achieve in patients with severe head injury; endoscopically guided placement is a better option. Endoscopic feeding tube placement most consistently allows for early enteral nutritional support in severe head injured patients. Limitations include the inability to establish and/or maintain enteral access, increased intracranial pressure, unstable cervical spinal injuries, facial fractures, and dedication of the physician to tube placement and monitoring.

Examination of baseline levels of carboxypeptidase N and complement components as potential predictors of angioedema associated with the use of an angiotensin-converting enzyme inhibitor.

OBJECTIVE: To determine if mean levels of complement components and carboxypeptidase N differed when comparing patients who exhibited angioedema following angiotensin-converting enzyme inhibitor therapy to those who received angiotensin-converting enzyme inhibitor therapy but did not have angioedema. DESIGN: Case-control study nested within an 8-week, open-label study of the use of quinapril hydrochloride for hypertension in 12275 patients. SETTING: Multicenter, with sites throughout the United States. PATIENTS: Of the 36 patients with angioedema described, 22 participated in the study. They were matched to 48 controls by age, sex, race, length of follow-up, and geographical region. INTERVENTION: All patients received quinapril therapy prior to participation in this case-control study. MAIN OUTCOME MEASURES: Levels of carboxypeptidase N, total hemolytic complement, C1 esterase inhibitor, and C4, along with questionnaire data, including a history of angioedema-like episodes and family history of angioedema. RESULTS: The 22 patients had significantly lower mean levels of carboxypeptidase N (kininase I) (P = .03) and C1 esterase inhibitor (P = .04) compared with the 48 matched controls, but all mean values were within normal laboratory ranges. A history of prior angioedema-like episodes was associated with an approximate 6-fold increase in the subsequent risk of angioedema following angiotensin-converting enzyme inhibitor therapy. CONCLUSIONS: Small differences in levels of carboxypeptidase N or C1 esterase inhibitor may contribute to an increased risk of angioedema with angiotensin-converting enzyme inhibitor therapy. Given the large overlap in the distributions of carboxypeptidase N and C1 esterase inhibitor levels, prior testing could not be used to evaluate angioedema risk for an individual patient considering angiotensin-converting enzyme inhibitor therapy. A history of prior angioedema-like episodes was associated with increased risk, but this result should be interpreted with caution because of possible recall bias.

Association of medically treated depression and age at natural menopause.

Between October 1989 and November 1992, the authors surveyed approximately 10,000 women between 45 and 54 years of age residing in western metropolitan Boston and selected as cases all women naturally menopausal before age 40 and a sample of women naturally menopausal between ages 40 and 46. Controls were a random sample of women who were premenopausal or naturally menopausal after age 47. Based on the results of an in-person interview to assess past reproductive and medical history, 14% of 344 cases compared with 6% of 344 controls reported a history of medically treated depression at least 1 year prior to menopause or comparable reference age in controls (adjusted odds ratio (OR) = 1.9, 95% confidence interval (CI) 1.1-3.3). The association of medically treated depression and early menopause was greatest in women naturally menopausal before age 40 compared with their age-and residence-matched controls (OR = 6.6, 95% CI 0.7-58.9) and in women who reported a history of medically treated depression that required more than 3 years of treatment (OR = 4.0, 95% CI = 1.3-12.0). This is the first study to suggest a link between a self-reported history of medically treated depression and early menopause. Additional studies are necessary to clarify the basis for this association.

A thiazole compound with potential antithrombotic activity.

A thiazole derivative, 4,5-bis(p-methoxyphenyl)-2-(trifluoromethyl)-thiazole was found to be a potent inhibitor of collagen-induced platelet aggregation, in vitro, using platelets from at at least six species, including man. It was active in human platelet-rich plasma at a concentration of 1 ng/ml. While its antiplatelet activity was greater than that of flurbiprofen, its cyclooxygenase activity was equivalent to that of flurbiprofen. Also, compared to flurbiprofen, the thiazole had less anti-inflammatory activity in the hind-paw edema test. The thiazole derivative inhibited platelet aggregation following oral administrative inhibited platelet aggregation following oral administration in five laboratory species. In the guinea pig it was active at 0.5 mg/kg. The LD50 in mice was greater than 1000 mg/kg (i.p.). This compound, which was designed through a systematic drug development program, may have high potential as an antithrombotic agent.

Synthesis and platelet aggregation inhibitory activity of 4,5-bis(aryl)-2-substituted-thiazoles.

In our continuing effort to discover compound which inhibit collagen-induced platelet aggregation, we have screened compounds in a mouse pulmonary thromboembolism screen. Methyl 4,5-bis(4-methoxyphenyl)-2-thiazoleacetate (3) was very active in the above screen. However, 3 was active for less than 5 min when given orally to guinea pigs. As a result, our synthetic goal was to prepare 2-substituted thiazoles with a much longer duration of activity. This paper describes the preparation of a number 4,5-bis(aryl)-2-substituted-thiazoles and their in vitro and ex vivo activity against collagen-induced platelet aggregation. It was determined that 4,5-bis(4-methoxyphenyl)-2-(trifluoromethyl)thiazole (16) is the most promising compound.