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1.
Ann Burns Fire Disasters ; 28(1): 39-45, 2015 Mar 31.
Article in English | MEDLINE | ID: mdl-26668561

ABSTRACT

The management of patients suffering from burn injury poses unique challenges for the reconstructive surgeon, both in the acute and delayed settings. Once resuscitative measures are optimized and hemodynamic stability is achieved, early burn debridement and coverage is performed. Traditionally, this consists of excision of devitalized tissue and subsequent coverage using split thickness skin grafts. However, in certain instances, and depending on the extent and nature of the burn injury, skin grafting (or even local tissue rearrangement) may not be a reasonable option. in these cases, free tissue transfer may provide a viable reconstructive alternative. While free flap reconstruction is rare in burn surgery, particularly in the acute setting, burn injuries that expose vital structures, such as tendon, nerve, bone, or deep vessels, require robust flap coverage. in the delayed setting, unsightly scar formation and contracture often occurs secondary to skin graft coverage. These significant patient morbidities are often amenable to free tissue transfer as well. This review article discusses the indications, applications, and problems with free flap surgery for burn injuries in both the acute and delayed setting, and summarizes the available literature on microsurgical free tissue transfer for burn management.


La prise en charge des patients atteints de brûlures pose des défis uniques pour le chirurgien de reconstruction, à la fois dans les cadres aigus et retardés. Une fois les mesures de réanimation sont optimisés et la stabilité hémodynamique est obtenue, il faut faire le débridement précoce et la couverture de la brûlure. Traditionnellement, il s'agit de l'excision des tissus dévitalisés et la couverture par division ultérieure en utilisant des greffes de peau partielle épaisse. Cependant, dans certains cas, et en fonction des dimensions et la nature de la brûlure, une greffe de peau n'est pas toujours une option raisonnable. Dans ces cas, le transfert de tissu libre peut fournir une alternative viable. Alors que la reconstruction de lambeau libre est rare dans la chirurgie des brûlures, en particulier dans le cadre aiguë, les brûlures qui exposent les structures vitales, telles que les tendons, nerfs, os, ou les vaisseaux profonds, nécessitent une couverture robuste. Dans le cadre retardé, la formation de cicatrices inesthétiques et de contractures se produit fréquemment secondaire à une couverture de greffe de peau. Souvent ces morbidités importantes sont aussi prêtent au transfert de tissu libre. Cet article de revue discute les indications, les applications, et des problèmes avec la chirurgie de lambeau libre pour des brûlures dans les cadres aigus et retardés. Cet article résume aussi la littérature disponible sur la microchirurgie du transfert de tissu libre pour la prise en charge des brûlures.

2.
Phys Med Biol ; 54(10): 3247-56, 2009 May 21.
Article in English | MEDLINE | ID: mdl-19420420

ABSTRACT

Diffraction-enhanced imaging (DEI) is a new x-ray imaging modality that has been shown to enhance contrast between normal and cancerous breast tissues. In this study, diffraction-enhanced imaging in computed tomography (DEI-CT) mode was used to quantitatively characterize the refraction contrasts of the organized structures associated with invasive human breast cancer. Using a high-sensitivity Si (3 3 3) reflection, the individual features of breast cancer, including masses, calcifications and spiculations, were observed. DEI-CT yields 14, 5 and 7 times higher CT numbers and 10, 9 and 6 times higher signal-to-noise ratios (SNR) for masses, calcifications and spiculations, respectively, as compared to conventional CT of the same specimen performed using the same detector, x-ray energy and dose. Furthermore, DEI-CT at ten times lower dose yields better SNR than conventional CT. In light of the recent development of a compact DEI prototype using an x-ray tube as its source, these results, acquired at a clinically relevant x-ray energy for which a pre-clinical DEI prototype currently exists, suggest the potential of clinical implementation of mammography with DEI-CT to provide high-contrast, high-resolution images of breast cancer (Parham 2006 PhD Dissertation University of North Carolina at Chapel Hill).


Subject(s)
Breast Neoplasms/diagnostic imaging , Mammography/methods , Radiographic Image Enhancement/methods , Refractometry/methods , Tomography, X-Ray Computed/methods , Humans , Reproducibility of Results , Sensitivity and Specificity
3.
Med Phys ; 32(2): 549-52, 2005 Feb.
Article in English | MEDLINE | ID: mdl-15789601

ABSTRACT

Conventional x-ray radiography measures the projected x-ray attenuation of an object. It requires attenuation differences to obtain contrast of embedded features. In general, the best absorption contrast is obtained at x-ray energies where the absorption is high, meaning a high absorbed dose. Diffraction-enhanced imaging (DEI) derives contrast from absorption, refraction, and extinction. The refraction angle image of DEI visualizes the spatial gradient of the projected electron density of the object. The projected electron density often correlates well with the projected mass density and projected absorption in soft-tissue imaging, yet the mass density is not an "energy"-dependent property of the object, as is the case of absorption. This simple difference can lead to imaging with less x-ray exposure or dose. In addition, the mass density image can be directly compared (i.e., a signal-to-noise comparison) with conventional radiography. We present the method of obtaining the mass density image, the results of experiments in which comparisons are made with radiography, and an application of the method to breast cancer imaging.


Subject(s)
Absorptiometry, Photon/methods , Algorithms , Breast Neoplasms/diagnostic imaging , Mammography/methods , Radiographic Image Enhancement/methods , Radiographic Image Interpretation, Computer-Assisted/methods , X-Ray Diffraction/methods , Absorptiometry, Photon/instrumentation , Humans , In Vitro Techniques , Mammography/instrumentation , Phantoms, Imaging , Reproducibility of Results , Sensitivity and Specificity , X-Ray Diffraction/instrumentation
4.
Inj Prev ; 9(4): 367-9, 2003 Dec.
Article in English | MEDLINE | ID: mdl-14693902

ABSTRACT

Permits to carry concealed firearms in public (CCW permits) remain controversial. A small scale natural experiment with shall-issue CCW permit policy in California, a may-issue state, is reported. During the mid-1990s, the chief of police of the Sacramento County town of Isleton issued permits to all county residents who applied and passed a standard background check. This program received national publicity. The incidence of subsequent criminal activity among 691 persons applying for CCW permits through Isleton's program in 1995 and that in a statewide sample of 965 CCW applicants from 1993-94 were compared. Subjects were followed up for three years from their application dates. The arrest rates for violent crime among Isleton and statewide applicants were 291 and 104 per 100 000 person-years, respectively (relative risk 2.8, 95% confidence interval 0.7 to 11.2, p = 0.18). This suggests that a shall-issue policy for CCW permits may result in higher rates of violent crime among permit holders, but the results do not reach statistical significance; larger studies are needed.


Subject(s)
Firearms/legislation & jurisprudence , Licensure/legislation & jurisprudence , Violence/statistics & numerical data , Adult , Aged , California/epidemiology , Female , Firearms/statistics & numerical data , Follow-Up Studies , Humans , Incidence , Licensure/statistics & numerical data , Male , Middle Aged
5.
New Dir Ment Health Serv ; (90): 77-89, 2001.
Article in English | MEDLINE | ID: mdl-11496511

ABSTRACT

Mental health consultation is provided to a municipal court that recommends court-mandated interventions for mentally ill persons who have committed minor crimes. This study demonstrates that a significantly better outcome results when the judge not only mandates but monitors mental health treatment.


Subject(s)
Community Mental Health Services/organization & administration , Criminal Law , Mental Disorders/rehabilitation , Prisoners , Adolescent , Adult , Aged , Aged, 80 and over , Female , Humans , Los Angeles , Male , Middle Aged , Prisoners/legislation & jurisprudence , Prisoners/psychology , Prisoners/statistics & numerical data
6.
Radiol Clin North Am ; 38(4): 861-9, x, 2000 Jul.
Article in English | MEDLINE | ID: mdl-10943283

ABSTRACT

Digital mammography allows for the separate optimization of image acquisition and display. Through this technology, and the application of image processing and computer aided diagnosis, breast cancer detection and breast lesion diagnosis might be improved. Besides the obvious data storage, retrieval, and transmission advantages that digital mammography will allow, additional advances such as tomosynthesis, dual energy mammography and digital subtraction mammography are in development. The possible future utility of Sestamibi breast scintigraphy and breast imaging with positron emission tomography is also discussed.


Subject(s)
Breast/diagnostic imaging , Mammography/methods , Radiographic Image Enhancement/methods , Radiopharmaceuticals , Technetium Tc 99m Sestamibi , Tomography, Emission-Computed , Breast Neoplasms/diagnostic imaging , Data Display , Diagnosis, Computer-Assisted , Female , Humans , Image Processing, Computer-Assisted/methods , Radiology Information Systems , Subtraction Technique
7.
N Engl J Med ; 341(21): 1583-9, 1999 Nov 18.
Article in English | MEDLINE | ID: mdl-10564689

ABSTRACT

BACKGROUND: There continues to be considerable controversy over whether ownership of a handgun increases or decreases the risk of violent death. METHODS: We conducted a population-based cohort study to compare mortality among 238,292 persons who purchased a handgun in California in 1991 with that in the general adult population of the state. The observation period began with the date of handgun purchase (15 days after the purchase application) and ended on December 31, 1996. The standardized mortality ratio (the ratio of the number of deaths among handgun purchasers to the number expected on the basis of age- and sex-specific rates among adults in California) was the principal outcome measure. RESULTS: In the first year after the purchase of a handgun, suicide was the leading cause of death among handgun purchasers, accounting for 24.5 percent of all deaths and 51.9 percent of deaths among women 21 to 44 years old. The increased risk of suicide by any method among handgun purchasers (standardized mortality ratio, 4.31) was attributable entirely to an excess risk of suicide with a firearm (standardized mortality ratio, 7.12). In the first week after the purchase of a handgun, the rate of suicide by means of firearms among purchasers (644 per 100,000 person-years) was 57 times as high as the adjusted rate in the general population. Mortality from all causes during the first year after the purchase of a handgun was greater than expected for women (standardized mortality ratio, 1.09), and the entire increase was attributable to the excess number of suicides by means of a firearm. As compared with the general population, handgun purchasers remained at increased risk for suicide by firearm over the study period of up to six years, and the excess risk among women in this cohort (standardized mortality ratio, 15.50) remained greater than that among men (standardized mortality ratio, 3.23). The risk of death by homicide with a firearm was elevated among women (standardized mortality ratio at one year, 2.20; at six years, 2.01) but low among men (standardized mortality ratio at one year, 0.84; at six years, 0.79). CONCLUSIONS: The purchase of a handgun is associated with a substantial increase in the risk of suicide by firearm and by any method; the increase in the risk of suicide by firearm is apparent within a week after the purchase of a handgun. The magnitude of the increase and the relation between handgun purchase and the risk of death by homicide differ between men and women.


Subject(s)
Firearms/statistics & numerical data , Mortality , Suicide/statistics & numerical data , Adult , Aged , California/epidemiology , Cause of Death , Cohort Studies , Female , Humans , Male , Middle Aged , Risk , Sex Factors , Time Factors
8.
Ann Emerg Med ; 32(1): 44-50, 1998 Jul.
Article in English | MEDLINE | ID: mdl-9656948

ABSTRACT

STUDY OBJECTIVE: We studied a population of young adults who legally purchased handguns to determine whether an association exists between the purchase of an assault-type handgun and prior or subsequent criminal activity. METHODS: We conducted a longitudinal study of 5,360 legally authorized purchasers of handguns in California in 1988 who were younger than 25 years at the time of purchase. Our main outcome measures were (1) adjusted relative risk (RR) for the purchase of an assault-type handgun for subjects with a criminal history compared with subjects without such a history and (2) adjusted RR for new criminal activity during the 3 years after handgun purchase for purchasers of assault-type handguns compared with purchasers of other handguns. RRs were adjusted for sex and race/ethnicity. RESULTS: Handgun purchasers with a criminal history were more likely than those with no criminal history to purchase assault-type handguns (4.6% and 2.0%, respectively; RR = 2.0; 95% confidence interval [CI] 1.5 to 2.8). Among handgun purchasers who had a criminal history, purchasers of assault-type handguns were more likely than purchasers of other handguns to be charged with new offenses (RR = 1.5; 95% CI, 1.3 to 1.9), including offenses involving firearms of violence (RR = 1.7; 95% CI, 1.3 to 2.20. Among those who had previously been charged with Violent Crime Index offenses (murder, rape, robbery, aggravated assault), those who purchased assault-type handguns were more than twice as likely as purchasers of other handguns to be charged with a new offense (RR = 2.3; 95% CI, 1.5 to 3.4) and three times as likely to be charged with a new offense involving firearms or violence (RR = 3.0, 95% CI, 1.9 to 4.6). CONCLUSION: In this population, the purchase of an assault-type handgun was associated with both prior and subsequent criminal activity.


Subject(s)
Firearms/statistics & numerical data , Violence/statistics & numerical data , Adolescent , Adult , Age Factors , California/epidemiology , Cohort Studies , Female , Humans , Longitudinal Studies , Male , Prevalence , Registries , Sex Factors , Violence/ethnology
9.
J Trauma ; 44(1): 155-60, 1998 Jan.
Article in English | MEDLINE | ID: mdl-9464765

ABSTRACT

OBJECTIVE: To determine whether there is an association between criminal activity and preference for a particular class of handgun among young adults who purchase handguns legally. DESIGN: Historical cohort study. MATERIALS AND METHODS: Subjects were 5,360 authorized purchasers of handguns in California in 1988 who were 21 to 25 years of age, divided into two groups: all eligible purchasers with a previous criminal history (n = 2,765), and a random sample of purchasers with no such history (n = 2,595). Handguns were classified as small and inexpensive or larger and expensive. Associations were assessed by relative risks adjusted for gender and race or ethnicity. MEASUREMENTS AND MAIN RESULTS: Handgun purchasers with a previous criminal history were more likely than those without such a history to purchase a small, inexpensive handgun (relative risk (RR) = 1.28; 95% confidence interval (CI), 1.16-1.42). Among handgun purchasers with no previous criminal history, those who purchased a small, inexpensive handgun were more likely than purchasers of other handguns to be charged with new crimes after handgun purchase (RR = 1.73; 95% CI, 1.34-2.24) and were nearly twice as likely to charged with new crimes involving firearms or violence (RR = 1.93; 95% CI, 1.38-2.69). CONCLUSION: In this population, criminal activity both before and after handgun purchase was associated with a preference for small, inexpensive handguns.


Subject(s)
Choice Behavior , Crime/psychology , Firearms , Adult , California , Cohort Studies , Crime/statistics & numerical data , Criminal Psychology , Ethnicity , Firearms/classification , Firearms/economics , Firearms/legislation & jurisprudence , Humans , Racial Groups , Registries , Risk , Sex Distribution
10.
JAMA ; 280(24): 2083-7, 1998.
Article in English | MEDLINE | ID: mdl-9875875

ABSTRACT

CONTEXT: Under current federal law, many persons with prior convictions for misdemeanor offenses pass criminal records background checks and legally purchase handguns. OBJECTIVE: To determine whether authorized handgun purchasers with prior misdemeanor convictions are more likely than those with no criminal history to be charged with new crimes, particularly offenses involving firearms and violence. DESIGN: Retrospective cohort study. SETTING AND PARTICIPANTS: A total of 5923 authorized purchasers of handguns in California in 1977 who were younger than 50 years, identified by random sample. MAIN OUTCOME MEASURES: Incidence and relative risk (RR) of first charges for new criminal offenses after handgun purchase. RESULTS: Of the 5923 authorized purchasers, 3128 had at least 1 conviction for a misdemeanor offense prior to handgun purchase, and 2795 had no prior criminal history. Follow-up to the end of the 15-year observation period or to death was available for 77.8% of study subjects and for a median 8.9 years for another 9.6%. Handgun purchasers with at least 1 prior misdemeanor conviction were more than 7 times as likely as those with no prior criminal history to be charged with a new offense after handgun purchase (RR, 7.5; 95% confidence interval [CI], 6.6-8.7). Among men, those with 2 or more prior convictions for misdemeanor violence were at greatest risk for nonviolent firearm-related offenses such as weapon carrying (RR, 11.7; 95% CI, 6.8-20.0), violent offenses generally (RR, 10.4; 95% CI, 6.9-15.8), and Violent Crime Index offenses (murder or non-negligent manslaughter, forcible rape, robbery, or aggravated assault) (RR, 15.1; 95% CI, 9.4-24.3). However, even handgun purchasers with only 1 prior misdemeanor conviction and no convictions for offenses involving firearms or violence were nearly 5 times as likely as those with no prior criminal history to be charged with new offenses involving firearms or violence. CONCLUSIONS: Handgun purchasers with prior misdemeanor convictions are at increased risk for future criminal activity, including violent and firearm-related crimes.


Subject(s)
Crime/statistics & numerical data , Firearms/legislation & jurisprudence , Adult , California/epidemiology , Female , Homicide/statistics & numerical data , Humans , Male , Retrospective Studies , Risk Factors , Violence/statistics & numerical data
11.
J Immunol ; 158(2): 604-13, 1997 Jan 15.
Article in English | MEDLINE | ID: mdl-8992974

ABSTRACT

BCRF1 is an EBV homologue of human IL-10 (hIL-10) and is known as viral IL-10 (vIL-10). As found earlier for the effects of vIL-10 on mouse mast cells and CD4+ T cells, the efficiency of inhibition by vIL-10 of IL-2 production by human CD4+ T cell clones is approximately 1000-fold diminished compared with hIL-10. We studied the interaction of vIL-10 and an epitope-tagged homologue, vIL-10His6, with recombinant mouse and human IL-10 receptors (mIL-10R, hIL-10R). vIL-10His6 has approximately 1000-fold lower affinity for recombinant IL-10R than does hIL-10, yet stimulates proliferation of mouse Ba/F3 (BaF)-mIL-10R- and human TF1-hIL-10R-transfected cells with a sp. act. comparable to or greater than that of the cellular cytokine. In contrast, BaF-hIL-10R cells are approximately 1000-fold less sensitive to vIL-10His6 than are BaF-mIL-10R cells. An anti-hIL-10R mAb (3F9) blocks responses to both hIL-10 and vIL-10His6, while a soluble form of hIL-10R effectively neutralizes biologic responses only to hIL-10 by both BaF-IL-10R transfectants and normal human peripheral blood cells. The results indicate that biologic responses to both hIL-10 and vIL-10 require the known IL-10R, and suggest the existence of at least one additional IL-10R subunit. We suggest that vIL-10 is a selective agonist that is impaired in its ability to bind the defined IL-10R, which we now designate as IL-10R alpha.


Subject(s)
Interleukin-10 , Receptors, Interleukin/agonists , Receptors, Interleukin/drug effects , Receptors, Interleukin/metabolism , Viral Proteins/immunology , Viral Proteins/pharmacology , Animals , Antibodies, Monoclonal/immunology , Cells, Cultured , Herpesvirus 4, Human/immunology , Herpesvirus 4, Human/metabolism , Humans , Interleukin-2/pharmacology , Leukocytes, Mononuclear/drug effects , Mice , Protein Binding/immunology , Receptors, Interleukin-10 , Recombinant Proteins/pharmacology , Viral Proteins/metabolism
12.
J Exp Med ; 185(1): 165-70, 1997 Jan 06.
Article in English | MEDLINE | ID: mdl-8996252

ABSTRACT

This paper describes an antibody (mAb 7D6) that specifically recognizes human follicular dendritic cells (FDCs). By expression cloning, a cDNA clone encoding for the long human CR2/ CD21 isoform (CD21L) that contains an additional exon (10a) was isolated. We demonstrated that FDCs selectively express CD21L, while B cells selectively express the short CR2/CD21 lacking exon 10a (CD21S). By screening mouse Ltk- cells transfected with the CD21L cDNA, we further showed that the other two anti-human FDC mAbs DRC-1 and KiM4 also recognize CD21L. Thus, CD21L represents the first characterized human FDC-specific molecule, which may confer unique functions of FDCs in germinal center development.


Subject(s)
Antigens, CD/biosynthesis , B-Lymphocytes/immunology , Dendritic Cells/immunology , Receptors, Complement 3d/biosynthesis , Animals , Antibodies, Monoclonal , Antigens, CD/genetics , Base Sequence , Child , Cloning, Molecular , DNA Primers , DNA, Complementary , Exons , Humans , L Cells , Mice , Mice, Inbred BALB C , Molecular Sequence Data , Palatine Tonsil/immunology , Polymerase Chain Reaction , Receptors, Complement 3d/genetics , Recombinant Proteins/biosynthesis , Transfection
13.
Am J Physiol ; 271(3 Pt 2): H1207-14, 1996 Sep.
Article in English | MEDLINE | ID: mdl-8853361

ABSTRACT

ATP-sensitive potassium channels are thought to play an important role in preconditioning. possibly due to shortening of the action potential duration (APD). The purpose of this study was to determine the effect of the class III antiarrhythmic agent dofetilide on preconditioning at a dose that abolishes APD shortening during ischemia A pilot study was performed to find a dose of dofetilide that would abolish the APD shortening effect of preconditioning Anesthetized dogs were subjected to 5-min coronary occlusion (or sham) and 10-min reperfusion followed by 60-min coronary occlusion. Monophasic action potentials were recorded periodically throughout the experiment. Significant APD shortening was observed during the 5- and 60-min ischemic periods, although preconditioning did not further enhance APD shortening during the prolonged ischemia. Dofetilide (1 mg/kg + 0.01 mg.kg-1.h-1 iv) abolished the APD shortening effect of ischemia. The effect of this dose of dofetilide on the protective action of preconditioning was then determined. Preconditioning significantly reduced infarct size expressed as a percentage of the area at risk compared with nonpreconditioned hearts. Dofetilide had no effect on infarct size when given to nonpreconditioned hearts. In addition, dofetilide did not alter the protective effect of preconditioning. No differences in collateral blood flow during ischemia were observed for any group. This study shows that the class III antiarrhythmic agent dofetilide does not abolish preconditioning and that the cardioprotective effect of preconditioning is independent of APD shortening below baseline values.


Subject(s)
Anti-Arrhythmia Agents/pharmacology , Ischemic Preconditioning, Myocardial , Phenethylamines/pharmacology , Potassium/antagonists & inhibitors , Sulfonamides/pharmacology , Action Potentials/drug effects , Animals , Coronary Circulation/drug effects , Dogs , Dose-Response Relationship, Drug , Female , Male , Myocardial Infarction/pathology , Myocardial Ischemia/physiopathology , Myocardial Reperfusion Injury/prevention & control , Pilot Projects , Reaction Time/drug effects
14.
Psychiatr Serv ; 47(3): 275-81, 1996 Mar.
Article in English | MEDLINE | ID: mdl-8820551

ABSTRACT

OBJECTIVE: The authors examined the outcomes of mental health consultation provided to a municipal court and the court's resulting interventions for mentally ill persons who committed minor crimes. One aim of the consultation program was to avoid criminalization of mentally ill people who committed minor offenses. METHODS: Clinical and forensic records of 96 persons charged with misdemeanors and referred to a clinical psychologist court consultant for evaluation were studied. Determination of good versus poor outcome during a one-year follow-up period was based on clients' status during the year after the court's disposition. Poor outcome was defined as the occurrence of one or more of four events during the follow-up year: psychiatric hospitalization, arrest, significant physical violence against persons, and homelessness. RESULTS: Fifty-six defendants (58 percent) were mandated to receive judicially monitored mental health treatment, as recommended by the psychologist court consultant, and 33 of them (59 percent) had a good one-year outcome. The relationship was statistically significant. CONCLUSIONS: Nonclinicians in the criminal justice system should have psychiatric assistance in making appropriate dispositions for mentally ill persons. If the judge is considering mental health treatment as a condition for eliminating or reducing punishment, then, to the extent justified by the law and the nature of the offense, the judge should both mandate and monitor the treatment on an ongoing basis.


Subject(s)
Criminal Law , Mental Disorders/psychology , Mental Disorders/rehabilitation , Mental Health Services/statistics & numerical data , Adolescent , Adult , Aged , Female , Hospitalization , Hospitals, Psychiatric , Humans , Male , Middle Aged , Retrospective Studies , United States
15.
J Pharmacol Exp Ther ; 276(2): 380-7, 1996 Feb.
Article in English | MEDLINE | ID: mdl-8632300

ABSTRACT

BMS-180448 has been found to retain the cardioprotective potency of its chemically related analog, cromakalim, although having significantly less peripheral vasodilating activity. The effect of the ATP-sensitive potassium channel opener, BMS-180448, on postischemic recovery of function (segmental shortening) was determined in open chested, anesthetized dogs instrumented with ultrasonic crystals. The plasma concentration of the effective and ineffective doses of BMS-180448 was compared to concentrations used in isolated rat hearts. BMS-180448 was given as a total dose of 4.2, 1.4 or 0.5 mg/kg over 30 min, starting 15 min before ischemia. Ischemia was initiated by a complete occlusion of the left anterior descending coronary artery for 15 min. Reperfusion was maintained for 3 hr and segmental shortening was measured. During ischemia, systolic bulging was observed in the ischemic region in drug- and vehicle-treated groups. Upon reperfusion, some contractile functional recovery was observed in vehicle-treated controls within minutes, but quickly decreased so that slight bulging was observed up to 3 hr into reperfusion. High dose BMS-180448 significantly improved the recovery of contractile function such that, by 3 hr after reperfusion, segmental shortening had recovered to 60% of base line. The 1.4-mg/kg dose also significantly improved reperfusion function, but 0.5 mg/kg of BMS-180448 was without effect. None of the doses of BMS-180448 significantly affected peripheral hemodynamic status or collateral blood flow. The plasma concentration of the 1.4-mg/kg dose was approximately 3 microM during ischemia. In isolated rat hearts, BMS-180448 significantly increased postischemic function at 3 microM and higher concentrations, which agrees with the dog data. BMS-180448 was protective in a dose-dependent manner in a canine model of stunned myocardium, and the concentrations necessary for protection are similar to that for rats.


Subject(s)
Benzopyrans/pharmacology , Cardiotonic Agents/pharmacology , Glyburide/antagonists & inhibitors , Guanidines/pharmacology , Myocardial Contraction/drug effects , Myocardial Ischemia/physiopathology , Potassium Channels/drug effects , Animals , Benzopyrans/blood , Dogs , Guanidines/blood , Male , Myocardial Stunning/physiopathology , Rats , Rats, Sprague-Dawley
16.
J Cardiovasc Pharmacol ; 26(2): 289-94, 1995 Aug.
Article in English | MEDLINE | ID: mdl-7475054

ABSTRACT

SQ 32,926 and SQ 32,547, two dihydropyrimidine calcium channel blockers, were characterized as potent inhibitors of depolarization-induced contractions of isolated smooth muscle preparations. In rat aorta, the IC50 values were 5.5 nM for SQ 32,547 and 8.1 nM for SQ 32,926, values which compare favorably with that of 2.9 nM for nifedipine. The dihydropyrimidines were also tested in a model of stable angina: pacing-induced ischemia in dogs. Both SQ 32,547 and SQ 32,926 reduced the ST-segment elevation observed in vehicle-treated animals. No significant changes in hemodynamic status were detected, suggesting that a reduction in cardiac work secondary to afterload reduction was probably not a major contributor to the protective effects. Neither was increased coronary blood flow important for the antiischemic outcome because no significant effects of the dihydropyrimidines were observed on ischemic regional blood flow. SQ 32,547 was also studied in globally ischemic, isolated rat hearts. In this model, SQ 32,547 was protective because it significantly reduced contracture formation and lactate dehydrogenase (LDH) release. Washing out the effect of SQ 32,547 in isolated hearts and smooth muscles was difficult, presumably due to its lipophilicity. In the smooth muscle preparations, the effects of both nifedipine and SQ 32,926 were much more easily washed out. As with other calcium channel blockers, increasing the antiischemic effects of SQ 32,547 was associated with a higher cost in terms of cardiac function. In summary, the two novel dihydropyrimidines, SQ 32,547 and SQ 32,926 showed antiischemic properties in animal models.


Subject(s)
Calcium Channel Blockers/pharmacology , Heart/drug effects , Piperidines/pharmacology , Pyrimidines/pharmacology , Animals , Dogs , Guinea Pigs , Hemodynamics/drug effects , In Vitro Techniques , Male , Muscle Contraction/drug effects , Myocardial Ischemia/drug therapy , Myocardial Ischemia/physiopathology , Rabbits , Rats , Rats, Sprague-Dawley , Swine
17.
J Cardiovasc Pharmacol ; 26(1): 145-52, 1995 Jul.
Article in English | MEDLINE | ID: mdl-7564356

ABSTRACT

We endeavored to determine if the enhanced shortening of the myocardial action potential duration (APD) during ischemia can be dissociated from the cardioprotective effects of the adenosine triphosphate (ATP) sensitive potassium channel (KATP) opener cromakalim. To establish if there is a relationship between APD shortening and the cardioprotective effect of cromakalim, we determined the effect of a dose of the delayed rectifier (IKr) blocker dofetilide (which abolishes the APD shortening effect of cromakalim) on the cardioprotective activity of cromakalim. Cromakalim was infused at a previously determined cardioprotective dose (10 micrograms/kg + 0.3 micrograms/kg/min infusion i.c.), and we determined the effect of 1 mg/kg (followed by a 0.01 mg/kg/min i.v. infusion) dofetilide alone and in combination with cromakalim on APD shortening and infarct size (90-min coronary occlusion and 5-h reperfusion) in anesthetized dogs. Dofetilide completely abolished the APD shortening effects of cromakalim during ischemia such that APD was similar to preischemic values. Cromakalim only shortened the APD during ischemia, although this effect was attenuated late into ischemia. Cromakalim significantly reduced infarct size (40% reduction from vehicle group value), whereas dofetilide alone had no effect. Dofetilide, at a dose that prevented the cromakalim-induced shortening of APD in ischemic tissue, did not attenuate the cardioprotective effects of cromakalim. No differences in collateral blood flow for any of the groups were observed. Dofetilide did cause a slight bradycardia, but this effect is unlikely to affect the interpretation of the results. These data suggest that APD shortening observed with the KATP opener cromakalim is not correlated with its cardioprotective effects.


Subject(s)
Anti-Arrhythmia Agents/pharmacology , Benzopyrans/pharmacology , Myocardial Ischemia/drug therapy , Myocardial Reperfusion Injury/prevention & control , Potassium Channels/drug effects , Pyrroles/pharmacology , Action Potentials/drug effects , Adenosine Triphosphate/pharmacology , Animals , Anti-Arrhythmia Agents/administration & dosage , Anti-Arrhythmia Agents/therapeutic use , Benzopyrans/administration & dosage , Benzopyrans/therapeutic use , Cromakalim , Dogs , Dose-Response Relationship, Drug , Drug Therapy, Combination , Female , Infusions, Intravenous , Male , Myocardial Ischemia/physiopathology , Myocardial Reperfusion Injury/physiopathology , Phenethylamines/administration & dosage , Phenethylamines/pharmacology , Phenethylamines/therapeutic use , Pyrroles/administration & dosage , Pyrroles/therapeutic use , Regional Blood Flow/drug effects , Sulfonamides/administration & dosage , Sulfonamides/pharmacology , Sulfonamides/therapeutic use
18.
Pharmacology ; 50(5): 286-97, 1995 May.
Article in English | MEDLINE | ID: mdl-7667390

ABSTRACT

Previous studies have indicated that structurally dissimilar serotonin2 (5HT2) antagonists can protect globally ischemic/reperfused reperfused rat hearts. We therefore determined if the 5HT2 antagonist cinanserin can protect the ischemic myocardium in two models of pacing-induced ischemia in anesthetized dogs. In one model, dogs were subjected to repeated 5-min episodes of pacing superimposed upon left anterior descending coronary artery stenosis such that an ST segment elevation of 10-11 mV was obtained and upon cessation of pacing, a return of ST segment elevation to baseline. In vehicle-treated animals, this ST segment elevation to baseline. In vehicle-treated animals, this ST segment elevation was constant for all pacing-induced ischemic episodes. After infusion of 20 micrograms/kg/min cinanserin (intracoronary, i.c.), ST segment elevation was significantly reduced during pacing-induced ischemia at all times measured postdrug. In the second model, animals were subjected to pacing-induced ischemia for 15 min such that segmental shortening was reduced to zero. Upon cessation of pacing-induced ischemia, recovery of shortening was assessed. In vehicle-treated dogs, function recovered to only 40% of baseline at 3 h into recovery. Pretreatment with 5 micrograms/kg/min cinanserin i.c. significantly improved recovery of postischemic function. In both protocols, cinanserin had no effect on ischemic regional blood flow or peripheral hemodynamics. Thus, cinanserin appears to exert profound protective effects in two models of effort-induced ischemia.


Subject(s)
Cinanserin/pharmacology , Heart/drug effects , Myocardial Ischemia/prevention & control , Analysis of Variance , Animals , Blood Platelets/drug effects , Cardiac Pacing, Artificial , Dogs , Electrocardiography/drug effects , Female , Heart/physiopathology , Hemodynamics/drug effects , Male , Myocardial Contraction/drug effects
19.
Clin Diagn Lab Immunol ; 1(1): 121-4, 1994 Jan.
Article in English | MEDLINE | ID: mdl-7496914

ABSTRACT

To characterize the human immune response to syphilis, we determined the effect of infection with Treponema pallidum on the percentage of the various lymphocyte subpopulations in the peripheral blood of infected and uninfected persons. Monoclonal antibodies labeled with either fluorescein isothiocyanate or phycoerythrin were used to perform dual color analysis on a FACScan with the following markers: CD3 for total T cells, CD4 for T helper cells, CD8 for T suppressor cells, CD19 for B cells, and CD16 plus CD56 for natural killer cells. Lymphocyte immunophenotype results were analyzed by the stage of untreated syphilis and by gender. Although they were within the ranges of the normal distribution of immunophenotypes, the percentages of CD4+ cells were significantly lower (P < 0.001) and those of CD8+ cells were higher (P = 0.03) in patients with syphilis than in the uninfected population. For infected versus uninfected subjects, both women and men, the differences in the mean percentages of CD3+ and CD4+ cells were significant (P < or = 0.05). Significant differences were noted between the sexes in secondary syphilis only in the mean percentages of cells positive for CD3, CD4, CD8, and CD16 plus CD56. Gender had no effect on lymphocyte subpopulations in subjects with primary or latent syphilis. In the control population, significant differences due to gender were observed in the percentages of cells positive for CD3, CD4, and CD16 plus CD56.


Subject(s)
Immunophenotyping , Lymphocyte Subsets/classification , Syphilis/immunology , Treponema pallidum/immunology , B-Lymphocytes/classification , B-Lymphocytes/immunology , Female , Flow Cytometry , Humans , Killer Cells, Natural/classification , Killer Cells, Natural/immunology , Lymphocyte Subsets/immunology , Male , T-Lymphocytes/classification , T-Lymphocytes/immunology
20.
Cardiovasc Res ; 27(9): 1613-8, 1993 Sep.
Article in English | MEDLINE | ID: mdl-8287438

ABSTRACT

OBJECTIVE: The aim was to determine the effect of the endothelin-1 receptor antagonist, BQ-123, on infarct size in anaesthetised dogs subjected to 90 min of left circumflex coronary artery occlusion and 5 h of reperfusion. METHODS: BQ-123 was given directly into the left circumflex coronary artery at 0.03 or 10 micrograms.kg-1 x min-1 starting 15 min before coronary occlusion and continuing throughout occlusion and reperfusion. Regional myocardial blood flow was determined before, during, and after ischaemia. At the end of the study, infarct size was determined using triphenyltetrazolium chloride staining. RESULTS: Myocardial infarct size was significantly reduced by BQ-123 (40% reduction from vehicle infarct size) at both doses used. This cardioprotection occurred despite a lack of effect of BQ-123 on peripheral haemodynamic status. BQ-123 also had no effect on regional myocardial blood flow in ischaemic and non-ischaemic tissue. Both cardioprotective doses of BQ-123 were found to completely abolish the coronary constrictor effect of intracoronary endothelin-1 administration. CONCLUSIONS: These data indicate that endothelin-1 release during ischaemia may be involved in the pathogenesis of myocardial ischaemia and infarction.


Subject(s)
Endothelin Receptor Antagonists , Myocardial Infarction/prevention & control , Peptides, Cyclic/administration & dosage , Animals , Coronary Vessels/drug effects , Disease Models, Animal , Dogs , Drug Administration Schedule , Endothelins/pharmacology , Female , Male , Myocardial Infarction/pathology , Myocardium/pathology , Peptides, Cyclic/therapeutic use
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