In vivo release and turnover of secreted platelet antiheparin proteins in rhesus monkey (Macaca mulatta)

Human and rhesus monkey platelets secrete at least two antiheparin proteins: platelet factor 4 (PF4) and low affinity platelet factor 4 (LA-PF4). Neither of these proteins showed species-related antigenic differences. As determined by radioimmunoassay, the levels of PF4 and LA-PF4 antigen per 10(9) monkey platelets amounted to 10.7 and 20.3 microgram, respectively. One milliliter of monkey plasma prepared from blood collected into an anticoagulant composed of EDTA, prostaglandin E1, and theophylline solution contained 22.4 ng LA-PF4 and 8.0 ng PF4. Concentrations of these two platelet-specific proteins in monkeys closely resembled levels found in human platelets and plasma. Infusion of prostacyclin (PGI2) (100 or 300 ng/kg/min) into monkeys for 15 min resulted in a significant decrease of plasma levels of LA-PF4 antigen and of PF4 by 40%--60% (p < 0.0001). This decrease was related to the inhibitory effect of PGI2 on the secretion of platelets stimulated by a catheter or by venipuncture. Longer infusion of PGI2 did not produce further significant change. The supernate obtained after aggregation of human platelets stimulated by thrombin was injected into monkeys receiving PGI2 infusion. The disappearance of LA-PF4 antigen in monkey plasma followed a biphasic exponential curve with half-lives for the fast and slow components of 8.4 and 63 min. PF4 disappeared faster but followed the same pattern (half-lives for the fast and slow component of 2.1 and 70 min). Analysis of the experimental data suggests that the low levels of secreted platelet proteins in monkey plasma are related to their minimal in vivo release and to their rapid clearance.     

儿童癌症幸存者成年后的慢性疾病

由于治疗方法的进步,近80%的儿童和青少年癌症患者能够长期生存。在美国,约有270000例儿童癌症的幸存者,即每640名20至39岁成年人中就有一名幸存者。大量的幸存者有利于儿童癌症治疗后长期健康结果的研究。现在可以明确的是,化疗和放疗所致的儿童各器官系统损害在临床上可能潜伏多年。为了全面了解治疗儿童癌症而继发的健康问题,重要的是衡量三项长期结果:健康状况、死亡率和患病率。这三项中,关于前两项已有相当好的研究报道。在一项对20227例癌症5年生存者的回顾性分析中,Mertens等发现以下原因导致的超额死亡率具有统计学意义:继发癌症(…     

Premature or Just Small? Training Guatemalan Birth Attendants to Weigh and Assess Gestational Age of Newborns: An Analysis of Outcomes

We describe Guatemalan birth attendants’ identification of vulnerable newborns, their evaluation of gestational age and anthropometry, and the validity of the Capurro and New Ballard newborn gestational age assessment methods. We interviewed 49 birth attendants and trained 10 of these women to assess 63 newborns. The Capurro and Ballard methods were correlated (Spearman rho = .75, p < .001) and showed agreement (Bland-Altman plot, difference and bias, ?0.33 ± 1.3 weeks). Prematurity was estimated at 27% (Ballard) and 24% (Capurro); low birth weight (LBW) was 30%. Capurro provided a simplified, equivalent estimate of gestational age compared with New Ballard that could be used by birth attendants.     

Continuous wave Doppler echocardiography after surgical repair of coarctation of the aorta

Objective—To find how closely pressure gradients across the aortic arch derived from Doppler echocardiography reflect gradients measured by catheter after surgical repair of coarctation of the aorta.Design—Pressure drop across the aortic arch was measured simultaneously by continuous wave Doppler and double lumen catheter in 20 patients with repaired coarctation of the aorta.Results—The peak pressure drop estimated by Doppler was almost invariably higher than the peak to peak gradient measured by catheter, as might be expected. Wide variation was seen between the Doppler measured pressure drop and instantaneous peak gradient measured by catheter, ranging from +22 to −17 mm Hg. The reasons for these differences are unclear but are probably related to a combination of complex flow dynamics in the aortic arch, difficulty in closely aligning the Doppler beam with flow, and inability to measure flow velocity immediately proximal to the site of the surgical repair with continuous wave Doppler.Conclusions—Continuous wave Doppler echocardiography may significantly overestimate or underestimate the pressure drop after repair of coarctation and it should be interpreted with caution in individual patients. Catheterisation with angiography remains the reference standard for assessment of surgical repair of the aortic arch.     

Transient bone marrow oedema: A variant pattern of sacral insufficiency fractures

A 71-year-old woman presenting with severe low back pain was found to have a large oval area of increased sacral uptake on Tc-99m MDP scan, with corresponding T1-hypointense and T2-hyperintense areas on magnetic resonance (MR) images, highly suggestive of malignancy. Open biopsies showed only callus formation. The patient responded clinically to conservative measures, with twice-repeated follow-up Tc-99m MDP and MR scans documenting resolution of transient bone marrow oedema. We suggest that this form of marrow oedema represents a variant pattern of sacral insufficiency fractures.     

Evaluation of a rapid stoolantigen test for the diagnosis of Helicobacter pylori infection in Chinese patients

OBJECTIVE: To evaluate the accuracy of a rapid assay that wasdeveloped to detect Helicobacter pylori antigen in the stool,using the principle of immunochromatography, in the Chinese population. METHODS: Eligible patients without prior treatment of H.pylori were recruited. An in‐house rapid urease test (RUT) andhistology were used as the gold standard. The results of the rapidstool antigen test were compared with the gold standard. RESULTS: Valid rapid stool antigen test results for interpretationwere obtained from 94 consecutive patients (mean age: 52.5, range:22?82 years). Sensitivity, specificity, positive predictivevalue, negative predictive value and accuracy were, respectively, 77.5%,87.0%, 81.6%, 83.9% and 83.0%.The test was easy to perform and results were available within 15 min. CONCLUSION: The rapid stool antigen test using immunochromatography accuratelydiagnoses H. pylori infection in Chinese patients.     

Robotic urological surgery in patients with prior abdominal operations is not associated with increased complications

BACKGROUND: The da Vinci Surgical Robotic System is being increasingly used to perform complex urological operations by minimally invasive techniques. Prior abdominal surgery associated with intra-abdominal adhesions may complicate robotic surgery. METHODS: We used a cohort of consecutive 49 patients undergoing a variety of robotic urological procedures at our institution to study the impact of prior abdominal operations on early perioperative complications. RESULTS: A total of 21/49 (43%) patients (Group A) had no history of prior abdominal surgery and the rest 28/49 (57%; Group B) had undergone prior abdominal surgery. The incidence of peritoneal adhesions was significantly higher in patients with prior abdominal surgery compared to the rest of the cohort, 54% versus 10% (P=0.002). The median operative time, estimated blood loss, postoperative drop in hemoglobin, time to hospital discharge, postoperative narcotic analgesic use and postoperative complication rate between group A and group B were not statistically different. The overall perioperative complication rate for the entire cohort was 14.3%, with 6-8% of complications occurring in each of the two groups (P=1.0). Comparative subset analysis of 28 patients in Group B, 15 (54%) and 13 (46%) with or without intra-abdominal adhesions did not reveal a significant difference in perioperative complication rates either. However, operative time was longer in patients with intra-abdominal adhesions compared to patients without, median of 590 (281-922) and 434 (153-723) min respectively, although not statistically significant (P=0.059). CONCLUSION: Our study demonstrates that robotic urological surgery can be performed in patients with prior abdominal surgery without increased perioperative complications.     

Depsides as non-redox inhibitors of leukotriene B(4) biosynthesis and HaCaT cell growth, 2. Novel analogues of obtusatic acid

Aseries of obtusatic acid analogues has been synthesized and evaluated as inhibitors of leukotriene B(4) (LTB(4)) biosynthesis and as antiproliferative agents. The 4-O-benzylated and the 4-O-demethylated congeners were the most potent inhibitors of LTB(4) production of the depside class of compounds, with IC(50) values in the submicromolar range. Furthermore, these compounds do not function as redox-based inhibitors because they were not reactive against a stable free radical, 2,2-diphenyl-1-picrylhydrazyl, and did not produce appreciable amounts of deoxyribose degradation as a measure of their potency to generate hydroxyl radicals. Some obtusatic acid congeners were also potent inhibitors of keratinocyte growth. Growth inhibition was not mediated by damage to the cell membrane, as the activity of lactate dehydrogenase released from the cytoplasm was in the control range.     

Nutritional correlates and dynamics of diabetes in the Nile rat (Arvicanthis niloticus): a novel model for diet-induced type 2 diabetes and the metabolic syndrome

Background

The prevalence of Metabolic Syndrome and related chronic diseases, among them non-insulin-dependent (type 2) diabetes mellitus, are on the rise in the United States and throughout the world. Animal models that respond to environmental stressors, such as diet, are useful for investigating the outcome and development of these related diseases.

Objective

Within this context, growth and energy relationships were characterized in the Nile rat, an exotic African rodent, as a potential animal model for diet-induced type 2 diabetes mellitus and Metabolic Syndrome.

Methods

Compiled data from several studies established the relationship between age, body weight gain (including abdominal adiposity), food and water consumption, and blood glucose levels as determinants of diabetes in male and female Nile rats. Glucose Tolerance Testing, insulin, HbA1c, blood pressure measurements and plasma lipids further characterized the diabetes in relation to criteria of the Metabolic Syndrome, while diet modification with high-fat, low-fiber or food restriction attempted to modulate the disease.

Results

The Nile rat fed lab chow demonstrates signs of the Metabolic Syndrome that evolve into diet-induced non-insulin-dependent (type 2) diabetes mellitus characterized by hyperinsulinemia with rising blood glucose (insulin resistance), abdominal adiposity, and impaired glucose clearance that precedes increased food and water intake, as well as elevated HbA1c, marked elevation in plasma triglycerides and cholesterol, microalbuminuria, and hypertension. Males are more prone than females with rapid progression to diabetes depending on the challenge diet. In males diabetes segregated into early-onset and late-onset groups, the former related to more rapid growth and greater growth efficiency for the calories consumed. Interestingly, no correlation was found between blood glucose and body mass index (overall adiposity) in older male Nile rats in long term studies, whereas blood glucose and the perirenal fat pad, as well as liver and kidney weight, were positively related to early-onset diabetes. Rats weaned early (4-5 wks) and challenged with a high-fat Western-type diet developed diabetes faster, and body fat accumulation was more apparent, whereas food restriction curtailed it.

Conclusion

The Nile rat fed typical rodent diets develops hyperinsulinemia that precedes hyperglycemia (insulin resistance) leading to diet-induced type 2 diabetes associated with hypertriglyceridemia, hypercholesterolemia, and hypertension. Dietary modulation affected growth rate (weight gain and central adiposity) to impact disease progression. This rodent model represents a novel system of gene-diet interactions affecting energy utilization that can provide insight into the prevention and treatment of the type 2 diabetes and Metabolic Syndrome.