Quantitative assessment of platelet function and clot structure in patients with severe coronary artery disease

RATIONALE AND OBJECTIVES: Although systemic absorption of enterically administered iohexol and its excretion in urine has been previously documented in rats with ischemic bowel, a practical and sensitive method of detecting urinary iohexol has not been available. We proposed to detect the presence of iohexol in the urine of rats with normal and ischemic bowel by use of a computed tomography (CT) number increase in the bladder with the use of CT. METHODS: Anesthetized rats (250 g) underwent either sham laparotomy (n = 6), ligation of two vascular arcades to the proximal jejunum (n = 5), ligation of six vascular arcades to the proximal jejunum (n = 6), or ligation of the superior mesenteric artery (n = 6). Rats were hydrated with saline (3.2 ml/hr intravenously). Each received a 3-ml enteric bolus of isotonic iohexol. Serial CT scans and plain film radiographs of the bladder were performed at 2, 4, and 6 hr to detect systemic absorption of contrast from the gut. Urine iohexol concentrations were measured by capillary electrophoresis. CT number and iohexol concentration were compared with evidence from plain film radiographs of bladder opacification. Intestinal ischemia was graded histologically. RESULTS: Histologic evidence of ischemia was present in all six-arcade and five of six superior mesenteric artery (SMA)-ligated animals. No animals in the control or two-arcade group showed evidence of bowel ischemia. Statistically significant increases (P < 0.05) in bladder density were demonstrated in the six-arcade and SMA-ligated groups. No statistical difference was noted between the two-arcade ligation and control groups. CONCLUSIONS: Experimental intestinal ischemia was reliably detected by bladder opacification after administration of enteric contrast. CT detection of systemic absorption of enteric iohexol was more sensitive than plain film radiographs and may be useful in the diagnosis of intestinal ischemia, although it may not be specific for ischemia.     

Misoprostol protection against acetaminophen-induced hepatotoxicity in the rat

The hepatoprotective effects of misoprostol on acetaminophen (APAP)-induced toxicity were studied in the rat. Liver injury was evaluated at 36 hr after APAP administration by measuring serum ornithine carbamoyltransferase (OCT) and alanine aminotransferase (ALT) levels, by using tetranitroblue tetrazolium (TNBT) staining and by histological analysis. After APAP administration, peak serum levels of the drug were detected at 15 min. Liver GSH was depleted from control levels of 448 +/- 48 micrograms/g to 82 +/- 2 micrograms/g (P < 0.01) within 3 hr. Serum ALT levels increased significantly after 16 hr and H&E staining revealed significant hepatic necrosis after 12 hr. Rats treated with misoprostol before and after APAP administration showed reduced OCT and ALT levels at 36 hr of overdose (454 +/- 446 IU/liter and 2571 +/- 2944 IU/liter, respectively) compared to those without misoprostol treatment (1348 +/- 480 IU/liter and 6077 +/- 3025 IU/liter, respectively, P < 0.01). TNBT staining showed a reduced area of damage from 28.6 +/- 22.3% to 7.3 +/- 8.9% (P < 0.01), and H&E staining also showed less extensive hepatic necrosis in rats treated with misoprostol before and after the overdose. In a time sequence study, misoprostol treatment starting within 10 hr of overdose showed the same protective effect as when it was given before and after APAP ingestion. No protection was detected when the treatment was started during the development of hepatic injury. However, misoprostol given when injury was established seemed to be protective. Our results show that misoprostol protects the liver against APAP-induced injury if given within 10 hr of overdose.(ABSTRACT TRUNCATED AT 250 WORDS)     

Biological characteristics and biomedical applications of the squid Sepioteuthis lessoniana cultured through multiple generations

Providing squids--especially their giant axons--for biomedical research has now been achieved in 10 mariculture trials extending through multiple generations. The noteworthy biological characteristics of Sepioteuthis lessoniana are (1) this species is behaviorally and morphologically well suited to the laboratory environment; (2) the life cycle is completed in 4-6 months; (3) growth is rapid (12% and 5% wet body weight d-1 for 100 d and for the life span, respectively), with adult size ranging from 0.4-2.2 kg; (4) feeding rates are high (30% wet body weight d-1), and a variety of live crustaceans and fishes are eaten; (5) crowding is tolerated (about 4 squids m-3); (6) the incidence of disease and cannibalism is low; and (7) reproduction in captivity allows culture through three successive generations. Engineering factors contributed to culture success: (1) physical design (i.e., size, shape, and painted pattern) of the culture tanks; (2) patterns of water flow in the culture tanks; (3) water filtration systems; and (4) spawning substrates. Initial production (a few hundred squids per year) suggests that large-scale culture will be able to supply the needs of the biomedical research community. The size (> 400 microns in diameter) and characteristics of the giant axons of Sepioteuthis are appropriate for experimentation, and other studies indicate that the eye, oculomotor/equilibrium system, olfactory system, blood, and ink are equally suitable for research.     

Encouraging attendance at a screening mammography programme: determinants of response to different recruitment strategies

Our objectives were 1) to determine the education attainment level (EAL) of parents attending the pediatric emergency department (PED); 2) to assess the readability level (RL) of the written instructions available to these parents; and 3) to revise these instruction forms at a level of comprehension based on the EAL of parents. We used a questionnaire of EAL and RL assessment using the SMOG and FOG readability formulas. We then revised the written instructions and used parents in the PED to pretest them. The setting was a PED in a tertiary care hospital (Children's Hospital of Western Ontario). The participants were 1034 parents of children in the PED between 8 AM and 11 PM over a six-month period. Parents were chosen at 30-minute intervals on randomly selected weekdays and weekends. A total of 1022 completed the study. Seven forms commonly used in the PED were assessed for RL. Seven forms were rewritten at grade 6 to 7 RL, and each was pretested in 21 of 24 parents or guardians in the PED using a standardized questionnaire with open-ended questions. Ninety percent of respondents spoke English, and 85% had English as their first language. Forty-nine percent of parents had a grade 13 or lower EAL. This included the following EALs; < grade 12 EAL, 23%; < grade 10 EAL, 15%; and < grade 8 EAL, 4%. Of the seven forms tested, five were written at a college RL. Pretesting of revised forms elicited the following responses from parents: easy to understand (100%), understood everything (96-100%), worth remembering (77-96%), liked the form (67-100%), found it informative (52-85%), and thought it was applicable to all people (82-100%).(ABSTRACT TRUNCATED AT 250 WORDS)     

ACE inhibitors and proteinuria

This review discusses the clinical consequences of urinary protein loss and the effects of inhibitors of the angiotensin converting enzyme (ACE) on this clinical finding. Proteinuria appears to be an important risk factor for renal function deterioration and for cardiovascular mortality. ACE inhibitors have been shown to reduce proteinuria more effectively than other antihypertensives. Their antiproteinuric effect seems to be independent of the underlying renal disease, and is mediated by a specific, not yet fully elucidated mechanism. Urinary protein loss related phenomena, such as hypoalbuminemia and aberrant lipoprotein profile, tend to improve also during ACE inhibitor treatment. Furthermore, ACE inhibition has been shown to prevent the renal function deterioration that is frequently observed in patients with renal disease. Interestingly, it has recently been shown that in proteinuric patients with renal disease the initial proteinuria lowering response to ACE inhibition predicts long-term renal function outcome during this treatment the more proteinuna is lowered during the first months, the better renal function will be preserved over the following years. Because of these favorable effects ACE inhibitors have become a widely used class of agents in nephrology. They are not only prescribed for lowering blood pressure in the hypertensive renal patient, but also as symptomatic treatment of patients with proteinuria, and to prevent renal function loss in patients with both diabetic and non-diabetic renal disease.     

The UL8 subunit of the herpes simplex virus type-1 DNA helicase-primase optimizes utilization of DNA templates covered by the homologous single-strand DNA-binding protein ICP8

The herpes simplex virus type-1 DNA helicase-primase is a heterotrimer encoded by the UL5, UL8, and UL52 genes. The core enzyme, specified by the UL5 and UL52 genes, retains DNA helicase, DNA-dependent nucleoside triphosphatase, and primase activities. The UL8 subunit has previously been implicated in increasing primer stability and in stimulating primer synthesis by the core enzyme. To further characterize the function of the UL8 subunit, we have examined its effect on the activities of the UL5/52 core enzyme using DNA templates covered by the herpes simplex virus type-1 single-strand DNA-binding protein ICP8. We found that while ICP8 stimulated the DNA helicase activity of the UL5/52 proteins up to 3-fold, maximum stimulation by ICP8 required the presence of UL8 protein. Moreover, UL8 protein was required to reverse the inhibitory effect of ICP8 on the DNA-dependent ATPase and primase activities of the UL5/52 proteins. These observations were specific for ICP8 since the heterologous Escherichia coli single-strand DNA-binding protein could not substitute for ICP8. These data suggest that UL8 protein mediates an interaction between the UL5/52 core enzyme and ICP8 that optimizes the utilization of ICP8-covered DNA templates during DNA replication.     

Catecholamines, stress, and disease: a psychobiological perspective

White demineralized areas after the removal of orthodontic appliances remain a problem for clinicians and patients. The main objective of this study is to assess clinical photography as a method for the evaluation of caries and white spots and the in vivo study of remineralization of carious lesions. The secondary objective was to compare the effect of different levels of both experimental and commercial fluoride solutions on the remineralization of enamel carious lesions. White spot lesions were created with an acid solution on extracted permanent human teeth, and the lesions were remineralized in remineralizing solutions with or without fluoride ions. The changes in the enamel surface during the demineralization and the remineralization processes were recorded with a 35 mm clinical camera. Photographs were taken of the experimentally created white spots, the samples were sectioned for microradiography testing, and the actual mineral contents of the white spot lesions were calculated from the microradiographs. The enamel lesions were further analyzed by powder x-ray diffraction to confirm whether fluoride was incorporated into the lesions during the remineralization period. From this experiment it can be concluded: (1) clinical photography as currently practiced is not an adequate method of monitoring the remineralization of white spots with large lesion depths and (2) the experimental solution that contains 50 ppm fluoride had a higher efficacy for remineralization than the control solution or the commercial mouth rinse, which contained 225 ppm fluoride.     

Intratumor pharmacokinetics, flow resistance, and metabolism during gemcitabine infusion in ex vivo perfused human small cell lung cancer

The Alcidae is a unique assemblage of Northern Hemisphere seabirds that forage by "flying" underwater. Despite obvious affinities among the species, their evolutionary relationships are unclear. We analyzed nucleotide sequences of 1,045 base pairs of the mitochondrial cytochrome b gene and allelic profiles for 37 allozyme loci in all 22 extant species. Trees were constructed on independent and combined data sets using maximum parsimony and distance methods that correct for superimposed changes. Alternative methods of analysis produced only minor differences in relationships that were supported strongly by bootstrapping or standard error tests. Combining sequence and allozyme data into a single analysis provided the greatest number of relationships receiving strong support. Addition of published morphological and ecological data did not improve support for any additional relationship. All analyses grouped species into six distinct lineages: (1) the dovekie (Alle alle) and auks, (2) guillemots, (3) brachyramphine murrelets, (4) synthliboramphine murrelets, (5) true auklets, and (6) the rhinoceros auklet (Cerorhinca monocerata) and puffins. The two murres (genus Uria) were sister taxa, and the black guillemot (Cepphus grylle) was basal to the other guillemots. The Asian subspecies of the marbled murrelet (Brachyramphus marmoratus perdix) was the most divergent brachyramphine murrelet, and two distinct lineages occurred within the synthliboramphine murrelets. Cassin's auklet (Ptychoramphus aleuticus) and the rhinoceros auklet were basal to the other auklets and puffins, respectively, and the Atlantic (Fratercula arctica) and horned (Fratercula corniculata) puffins were sister taxa. Several relationships among tribes, among the dovekie and auks, and among the auklets could not be resolved but resembled "star" phylogenies indicative of adaptive radiations at different depths within the trees.     

Fixation conditions, the foveola and saccadic latency

Saccades are often elicited in the laboratory by the abrupt step-displacement of a single lit point which is initially the foveolar fixation point and then the eccentric refixation target. This was our Control condition. Four experiments modified the fixation arrangements to examine the effect of altered foveolar stimulation on saccadic latency and accuracy to targets within the central +/- 6 deg of the visual field. (1) No foveolar fixation point: The subject fixated the empty space midway between a pair of fixation guides, which later collapsed into a single refixation target. Latencies for small saccades were similar to the Control values. (2) No foveolar fixation point and no real refixation target: A pair of fixation guides underwent a yoked displacement, and it was easy to fixate and track the invisible midpoint. The smallest saccades were hypermetric, and the typical pattern of latency variation with retinal eccentricity was exaggerated in scale. (3) Spatial effects of a persistent non-target: The precise position of a non-target was important, latency increases being in the ipsilateral hemifield when the non-target was intrafoveolar and unilateral, bilateral when intrafoveolar and on the midline, and local when the non-target was extrafoveolar. (4) Temporal effects of a foveolar fixation point: Blanking an otherwise persistent fixation point for as little as 1 msec at the time of target presentation reduced the expected latency increase. We conclude that the position and timing of foveolar illumination can be critical for saccades of all sizes.