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Biomedical subjects

P Chang

Publications and source records attributed to P Chang.

At least 163 records · Page 9Linked to original sources
PubMed1996

Activated factor VIII in therapeutic preparations: analysis by ultracentrifugation.

Activation of factor VIII is signaled by an increase in the 1-stage factor VIII activity and release from von Willebrand factor. Ultracentrifugation in 10-40% sucrose gradients was used to identify such activation in therapeutic concentrates. Plasma-derived factor VIII lots were examined and factor VIII sedimenting independently of von Willebrand factor was identified in some of the preparations. In addition there was slower sedimentation of factor VIII by the 1-stage assay than by the chromogenic assay. These results are consistent with a factor VIII cleaved at residue 1689, a site important for von Willebrand binding. This activated form leads to some of the assay discrepancies between the 1-stage assay and the chromogenic or the 2-stage assay. There is more rapid sedimentation of the factor VIII measured by the chromogenic assay than the von Willebrand factor in some manufacturers' samples indicating that the method of fractionation may select a low molecular weight von Willebrand factor which does not bind factor VIII. Routine comparison between the 1-stage and chromogenic assays during fractionation may be able to identify such activated preparations. Other assay discrepancies may be due to structural differences between the standards and the tested product.

Factor VIIIa↗
PubMed1996

The role of neovascularization in the survival of an arterialized venous flap.

This study compares survival of arterialized venous flaps placed on normal and impaired recipient beds in New Zealand White rabbit ear. Fasciocutanous flaps (4 x 5 cm) were perfused by an arteriovenous anastomosis; outflow was provided by one vein. In group 1, the arterialized venous flap was sutured into its bed on the ear; in group 2, a sheet of silicone was placed between the flap and the ear, providing an experimentally impaired recipient bed. Flap survival was expressed as a percentage of the total flap surface by means of a computerized image analysis system. Excellent survival (> or =95 percent) was noted in 16 of 21 arterialized venous flaps in group 1 versus 2 of 21 in group 2 (p < 0.01). Partial survival (50 to 94 percent) was observed in 2 of 21 arterialized venous flaps in group 1 and 15 of 21 in group 2. Poor survival (<50 percent) was noted in 3 of 21 in group 1 and in 4 of 21 in group 2. Microangiography was used to illustrate arteriovenous fistulas, the vascular network within the flaps, and neovessels in the periphery of the flaps. These data indicate that neovascularization is necessary for optimal survival of arterialized venous flaps in this experimental rabbit ear model.

Animals↗
PubMed1996

Infant hearing screening with an automated auditory brainstem response screener and the auditory brainstem response.

From 1653 babies hospitalized in the Veterans General Hospital-Taipei from 1993 to 1995, 260 infants at risk of hearing impairment were selected. The risk criteria of hearing impairment for neonates were based on the recommendation of the US Joint Committee on Infant Hearing, 1990 Position Statement. All these infants were screened with the Algo-1 Plus, an automated auditory brainstem response (ABR) screener at a mean postconceptional age of 40.7 +/- 4.5 weeks. Thirty-nine cases (39/260, 15%) involving 57 ears (57/520, 11%), failed the screening. Except for one infant who died, the babies had an ABR test for both air- and bone-conducted stimuli and an otological examination. The case-specific incidence of conductive hearing deficit at the initial ABR test was 5.4%. The prevalence of sensorineural hearing deficits was between 2.3% confirmed and 3.1% including infants who did not have follow-up tests. The kappa-value that indicated agreement between the Algo-1 and ABR results was 0.64, and the overall efficiency of using Algo-1 to correctly identify pass or failure of the ABR was 83%.

Audiometry, Evoked Response↗
PubMed1996

Early gene expression along the animal-vegetal axis in sea urchin embryoids and grafted embryos.

The HE gene is the earliest strictly zygotic gene activated during sea urchin embryogenesis. It is transiently expressed in a radially symmetrical domain covering the animal-most two-thirds of the blastula. The border of this domain, which is orthogonal to the primordial animal-vegetal axis, is shifted towards the animal pole in Li+-treated embryos. Exogenous micromeres implanted at the animal pole of whole embryos, animal or vegetal halves do not modify the extent and localization of the HE expression domain. In grafted embryos or animal halves, the Li+ effect is not affected by the presence of ectopic micromeres at the animal pole. A Li+-induced shift of the border, similar to that seen in whole embryos, occurs in embryoids developing from animal halves isolated from 8-cell stage embryos or dissected from unfertilised eggs. Therefore, the spatial restriction of the HE gene is not controlled by the inductive cascade emanating from the micromeres and the patterning along the AV-axis revealed by Li+ does not require interactions between cells from the animal and vegetal halves. This suggests that maternal primary patterning in the sea urchin embryo is not limited to a small vegetal center but extends along the entire AV axis.

Animals↗
PubMed1996

Reduction mammaplasty: the results of avoiding nipple-areolar amputation in cases of extreme hypertrophy.

In extreme cases of breast hypertrophy, amputation of the nipple-areolar complex and transplantation during reduction mammaplasty has been advocated to avoid nipple necrosis. We report our experience with 172 patients having inferior breast pedicle reduction without amputation of the nipple-areolar complex. Mean total weight of resected tissue was 1,946 g (548 to 5,100 g), with a mean nipple-areolar transposition of 10 cm (0.5 to 23 cm). Dividing patients into four groups by weight of resection, we compared complication rates. In this series, where nipple-areola amputation was avoided, there was a 99.6% survival rate of the nipple-areolar complex with 97.1% retention of nipple sensibility. Patients with extreme breast hypertrophy (3,000 g resected tissue) experienced no increase in complications when compared to smaller reductions. In most cases of gigantomastia, amputation of the nipple can be avoided using the inferior breast pedicle technique. Size of breast resection alone should not determine the fate of the nipple.

Adolescent↗
PubMed1996

Immunodetection of cytoskeletal structures and the Eg5 motor protein on deep-etch replicas of Xenopus egg cortices isolated during the cortical rotation.

We have developed a new method for immunogold detection on deep-etch replicas of isolated Xenopus egg cortices in order to examine the interactions of different cortical elements in three dimensions at high resolution. We have applied this technique to vegetal cortices isolated during the second half of the first cell cycle. The vegetal cortical region at this time is the site of cellular machinery responsible for the 'cortical rotation'. The entire cortex translocates with respect to the inner cytoplasm, relocating dorsalising determinants to the future dorsal side of the egg. The aligned microtubules in the shear zone between cytoplasm and cortex, implicated in the cortical rotation, were found to be organised as interweaving loose bundles. Interleaved amongst these aligned microtubules were extensive sheets of ER lying in layers parallel to the egg surface. Cytokeratin filaments were found to associate closely with the microtubules over short stretches. Putative actin filaments were present in the shear zone and in the cortex. Eg5, an abundant kinesin-related microtubule motor protein, and candidate for a role in generating cortical rotation movement, showed an almost exclusive localisation to microtubules. Immunofluorescence studies of cortices treated with detergent to disrupt ER or cold to depolymerise microtubules confirmed that Eg5 associates primarily with microtubules. We propose revised models for the mechanism of cortical rotation based on these observations and conclude that Eg5 is unlikely to move ER relative to microtubules during the cortical rotation.

Animals↗
PubMed1995

Coagulant proteins and thrombin generation in synovial fluid: a model for extravascular coagulation.

The coagulant content and thrombin generating potential of synovial fluid from patients with osteoarthritis were studied as a model of extravascular coagulation. The concentrations of individual coagulant proteins were partially correlated with their molecular weight. The levels of the very large coagulants factor V, factor VIII and von Willebrand factor antigen (vWF:ag) are less than 1% of the activities found in a normal pooled reference plasma while smaller coagulants including factors IX, XI and prothrombin range between 9 and 30%. The protease inhibitors antithrombin-III (AT-III) and Alpha-2 macroglobulin in synovial fluid were present at levels of 74% and 13% of plasma, higher than expected based on their molecular weights. Prothrombin was more rapidly activated by tissue thromboplastin than by aPTT reagent. The thrombin activity formed in synovial fluid decreased more rapidly than that formed in dilute plasma. The addition of recombinant factor VIII or bovine factor V to synovial fluid accelerated the thrombin production by APTT but not by tissue thromboplastin. Indicating that the low levels of factor VIII and factor V did limit the rate of thrombin production. The addition of specific antibodies to factor VIII or factor V strongly inhibited thrombin production by aPTT. These data confirm a roughly inverse relationship between the concentrations of coagulation proteins and their molecular weight in synovial fluid and indicate that thrombin can be generated in synovial fluid. The inactivation of thrombin in synovial fluid may be more dependent on antithrombin-III than in plasma because of the increased AT-III/alpha-2 macroglobulin ratio seen in synovial fluid.

Animals↗
PubMed1995

Angiotensin II receptor antagonists in heart failure: rationale and design of the evaluation of losartan in the elderly (ELITE) trial.

Angiotensin-converting enzyme inhibitors (ACE-I) have been proven to be effective in reducing morbidity and mortality in patients with heart failure or post-myocardial infarction left ventricular dysfunction. Despite evidence from several large-scale randomized trials, the use of ACE-I in patients with heart failure remains relatively low. In part, the failure to achieve more widespread use of ACE-I in patients with heart failure may be due to physician's perceptions of the side effects associated with ACE-I, such as angioedema, renal dysfunction, cough, and hypotension. Many of these side effects are thought to be due to ACE-I-induced bradykinin accumulation. It is possible to inhibit the effect of angiotensin II without increasing bradykinin levels using an angiotensin II type I blocking agent such as losartan. How effective losartan is compared with an ACE-I is uncertain, however. Some of the beneficial effects of ACE-I have been attributed to bradykinin accumulation, and therefore ACE-I might have an advantage compared with an angiotensin II type I receptor antagonist such as losartan. On the other hand, angiotensin II may be produced by non-ACE-I-dependent mechanisms, which would suggest that an angiotensin II type I receptor blocking agent would be advantageous. To determine the relative safety and efficacy of an ACE-I, which results in bradykinin accumulation and inhibitors of angiotensin II, versus an angiotensin II type I receptor blocking agent, which does not result in bradykinin accumulation, we have begun the Evaluation of Losartan In The Elderly (ELITE) trial, which will compare the safety and efficacy of captopril and losartan in elderly patients with heart failure.

Aged↗
PubMed1995

Analysis of changes in coagulation factors after postoperative blood loss in burn and non-burn patients.

A prospective study of the postoperative kinetics of coagulation factors was undertaken in 23 burn patients and in six non-burn patients. All procedures resulted in a large volume blood loss. Fibrinogen, platelets and factors V, VIII and IX were measured serially. Burn patients returned all parameters to preoperative levels by 48 h postoperation, while non-burn patients showed a slower rate of return of platelets and factor V. This study suggests that burn patients may safely undergo re-operation at 48 h intervals for successive wound debridements if clinically necessary.

Adolescent↗
PubMed1995

Comparison of the effects of losartan and enalapril on clinical status and exercise performance in patients with moderate or severe chronic heart failure.

OBJECTIVES: This study assessed the feasibility of an efficacy trial comparing angiotensin-converting enzyme inhibition and angiotensin II receptor antagonism in heart failure. Patients with moderate or severe heart failure whose condition had previously been stabilized by treatment with a converting enzyme inhibitor were randomly assigned to receive enalapril or losartan. The study was designed to detect any signs of clinical deterioration during double-blind treatment. BACKGROUND: Losartan is a specific, nonpeptide angiotensin II receptor-1 antagonist with a vasodilator hemodynamic profile similar to that of converting enzyme inhibitors. Although therapy with specific receptor blockade has certain theoretic advantages over nonspecific converting enzyme inhibition, demonstration of a comparable therapeutic effect in patients with congestive heart failure will require a major effort comparing two active agents. METHODS: One hundred sixty-six patients with stable heart failure in New York Heart Association functional class III or IV and an ejection fraction < or = 35% were included in a multicenter, double-blind, parallel, enalapril-controlled trial. After a 3-week stabilization period with optimal therapy, including digitalis, diuretic drugs and a converting enzyme inhibitor, patients were randomly assigned to 8 weeks of therapy with losartan, 25 mg/day (n = 52); losartan, 50 mg/day (n = 56); or enalapril, 20 mg/day (n = 58). Patients were assessed with frequent clinical and laboratory evaluation and exercise testing. RESULTS: No significant differences between groups in terms of changes in exercise capacity (6-min walk test), clinical status (dyspnea-fatigue index), neurohumoral activation (norepinephrine, N-terminal atrial natriuretic factor), laboratory evaluation or incidence of adverse experience were observed. CONCLUSIONS: The results suggest that losartan and enalapril are of comparable efficacy and tolerability in the short-term treatment of moderate or severe congestive heart failure. A trial designed to compare the efficacy, tolerability and effect on mortality of long-term angiotensin II receptor blockade with converting enzyme inhibition is both feasible and ethically responsible.

Adult↗
PubMed1995

Extracellular and standard University of Wisconsin solutions provide equivalent preservation of myocardial function.

The deleterious effect of hyperkalemic cardioplegic solutions on coronary endothelium has been documented and has also been demonstrated with University of Wisconsin solution. We evaluated a new extracellular University of Wisconsin formulation for efficacy in heart preservation. Six neonatal piglet hearts were arrested with and stored in the standard intracellular University of Wisconsin solution (group 1: K+ 125 mEq/L, Na+ 29 mEq/L). Six piglet hearts were preserved for 24 hours with an extracellular University of Wisconsin solution that differed only in the concentrations of potassium and sodium (group 2: K+ 25 mEq/L, Na+ 129 mEq/L). Hearts underwent modified reperfusion with leukocyte-depleted aspartate-glutamate enriched blood cardioplegic solution followed by conversion to a left-sided working mode on a Langendorff circuit with perfusion from a support pig. Stroke work index was calculated at left ventricular end-diastolic pressures of 3, 6, 9, and 12 mm Hg. Sixty minutes after reperfusion, there was no significant difference in stroke work index between group 1 (16.4 +/- 1.9 x 1000 erg/gm) and group 2 (15.3 +/- 2.7 x 1000 erg/gm). There was also no significant difference in high-energy phosphate stores or myocardial water content between the two groups. Extracellular University of Wisconsin solution provides myocardial preservation equivalent to standard University of Wisconsin solution while preventing exposure of coronary endothelium to high levels of potassium, which justifies its use in clinical heart transplantation.

Adenosine↗
PubMed1995

The regional capillary distribution of retrograde blood cardioplegia in explanted human hearts.

Warm retrograde blood cardioplegia is frequently used for myocardial protection, despite experimental studies questioning the adequacy of capillary flow to the right ventricle and septum. The capillary distribution of retrograde blood cardioplegia in the human heart is unknown. Hearts from eight transplant recipients with the diagnosis of idiopathic or dilated cardiomyopathy were arrested in situ with cold blood cardioplegia and excised with the coronary sinus intact. Within 20 minutes of explanation, colored microspheres mixed in 37 degrees C blood cardioplegia were administered through the coronary sinus at a pressure of 30 to 40 mm Hg for 2 minutes. Twelve transmural myocardial samples were taken horizontally at the level of midventricle and apex to determine regional capillary flow rates. When retrograde warm blood cardioplegia was administered at a rate of 0.42 +/- 0.06 ml/gm/min, the left ventricle, the septum, the posterior wall of the right ventricle, and the apex consistently received capillary flow rates in excess of their metabolic requirements. The capillary perfusion of anterior and lateral walls of the right ventricle was marginally adequate to sustain aerobic metabolism. In explanted human hearts, retrograde blood cardioplegia provides adequate capillary flow to the left ventricle, the septum, the posterior wall of the right ventricle, and the apex; however, capillary flow to the anterior and lateral walls of the right ventricle is marginal. This study delineates the tenuous balance between supply and demand for right ventricular protection with warm continuous retrograde blood cardioplegia.

Capillaries↗
PubMed1995

Coronary sinus ostial occlusion during retrograde delivery of cardioplegic solution significantly improves cardioplegic distribution and efficacy.

UNLABELLED: This study documents the gross flow characteristics and capillary distribution of cardioplegic solution delivered retrogradely with the coronary sinus open versus closed. METHODS: Five explanted human hearts from transplant recipients were used as experimental models. Hearts served as their own controls and received two doses of warm blood cardioplegic solution, each containing colored microspheres. The first dose was delivered through a retroperfusion catheter with the coronary sinus open and the second dose was delivered with the sinus occluded. Capillary flow was measured at twelve ventricular sites and gross flow was measured by examining coronary sinus regurgitation, thebesian vein drainage, and aortic effluent (nutrient flow). RESULTS: Coronary sinus ostial occlusion allowed for a significant decrease in total cardioplegic flow (1.74 +/- 0.40 ml/gm versus 1.06 +/- 0.32 ml/gm; p < 0.05) to occur while maintaining an identical intracoronary sinus pressure. Ostial occlusion also resulted in an increase in the ratio of nutrient flow/total cardioplegic flow from 32.3% +/- 15.1% to 61.3% +/- 7.9% (p < 0.05). A statistically significant improvement in capillary flow was found at the midventricular level in the posterior intraventricular septum and posterolateral right ventricular free wall. This improvement was also documented for the intraventricular septum and right ventricle at the level of the apex. CONCLUSION: Coronary sinus occlusion during retrograde cardioplegia significantly improves cardioplegic delivery to the right ventricle and posterior intraventricular septum. Furthermore, the technique affords a significant improvement in nutrient cardioplegic flow while reducing the overall volume of cardioplegic solution administered.

Capillaries↗