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G J Whitman

Publications and source records attributed to G J Whitman.

At least 37 records · Page 2Linked to original sources
PubMed1998

Acute administration of liposomal coenzyme Q10 increases myocardial tissue levels and improves tolerance to ischemia reperfusion injury.

UNLABELLED: The antioxidant and bioenergetic effects of CoQ10 (CoQ) suggest it might be ideal therapy for acute myocardial ischemia. Its utility is limited by the requirement for enteral administration. This study related the administration of a new liposomal suspension of CoQ given intravenously to (1) serum and myocardial [CoQ] and (2) recovery of function, myocardial efficiency, and oxidant injury after cardiac ischemia and reperfusion (I/R). Rats (n = 8/group) were given liposomal CoQ 10 mg/kg iv or placebo (Control), 15 min (C-15), 30 min (C-30), and 60 min (C-60) before (1) measurement of serum and myocardial CoQ or (2) Langendorff perfusion of hearts subjected to 15 min equilibration, 25 min ischemia (37 degrees C), and 40 min reperfusion (RP). Developed pressure (DP) was measured via an intraventricular balloon and coronary flow was measured by a digital flow meter. Myocardial efficiency was defined as DP/MVO2 where MVO2 = microl O2 consumed/min/gram LV. At end RP hearts were assayed for CK, an oxidant sensitive enzyme. Maximum preischemic CoQ levels in serum and myocardium occurred 15 and 30 min after administration, respectively. At end reperfusion, C-30 hearts improved the most, recovering 75 +/- 4% of their preischemic DP while Control recovered only 52 +/- 6% (P < 0.03) as well as maintaining better myocardial efficiency (0.69 +/- 0.02 vs Control, 0.43 +/- 0.05) (P < 0.001). C-15, C-30, and C-60 groups all lost less CK activity after RP vs Control (P < 0.04). CONCLUSION: (1) Serum and myocardial levels of CoQ can be raised acutely by iv liposomal CoQ. (2) Myocardial CoQ levels correlate best with I/R protection. (3) Acute iv CoQ improves function and efficiency and decreases oxidant injury after I/R. Intravenous CoQ may be effective clinically for acute cardiac ischemic syndromes.

Animals↗
PubMed1998

Negative mammograms in symptomatic patients with breast cancer.

RATIONALE AND OBJECTIVES: To determine the limitations of mammography in symptomatic patients. MATERIALS AND METHODS: Approximately 20,000 mammograms obtained during a 2-year period were correlated with the results of a retrospective review of the pathology database, which revealed 711 patients with breast cancer. A total of 496 of these patients underwent mammography at the authors' institution. Three observers reviewed the mammograms of patients with "normal" mammograms within 6 months of excisional biopsy. The parenchymal patterns were also assessed. RESULTS: Mammographic abnormalities were identified in 481 cases (97%), and 15 mammograms (3%) were interpreted as "unremarkable." Fourteen of the unremarkable cases were available for review, which indicated nine true-negative findings, one technical error, two observer errors, and two combined technical and observer errors. The technical error involved the lower inner quadrant of the breast, adjacent to the chest wall. All 14 mammograms were of dense breasts. CONCLUSION: Mammographic abnormalities were identified in nearly all patients with proved breast cancer. Mammograms in which lesions were missed were of dense breasts, but one-third of the lesions were visible in retrospect. When examining symptomatic patients with dense breasts, radiologists should use optimal mammographic techniques and consider using nonmammographic breast imaging modalities.

Adult↗
PubMed1998

Pyruvate improves myocardial tolerance to reperfusion injury by acting as an antioxidant: a chemiluminescence study.

BACKGROUND: There is indirect evidence that pyruvate improves myocardial tolerance to ischemia by scavenging oxygen radicals during reperfusion. The objectives of this study were to evaluate (1) lucigenin-enhanced chemiluminescence (LEC) as a method to measure oxygen radical (OR) production in vitro and in vivo and (2) the antioxidant effect of pyruvate during myocardial reperfusion. METHODS: LEC was measured in vitro by adding to lucigenin (1) increasing concentrations of H2O2, (2) H2O2 and different concentrations of catalase, and (3) H2O2 plus pyruvate. Isolated rat hearts perfused with Krebs Henseleit-Lucigenin inside a chemiluminescence chamber were subjected to equilibration, ischemia, and reperfusion without (control) or with pyruvate. Developed pressure, contractility, compliance, and chemiluminescence were recorded. RESULTS: In vitro, LEC directly correlated with H2O2 concentrations (r2 = 0.997) and decreased in the presence of catalase or pyruvate. During myocardial reperfusion there was a surge of chemiluminescence that peaked at 4 minutes. Pyruvate decreased the initial reperfusion peak (9.8 +/- 0.3 x 10(3) cpm in pyruvate group vs 12.4 +/- 0.9 x 10(3) cpm in control; p < 0.05) and the total amount of chemiluminescence generated during reperfusion (65.7 +/- 12 x 10(3) in pyruvate group vs 117.1 +/- 8.2 x 10(3) counts in control; p < 0.05). Pyruvate improved recovery of function after ischemia reperfusion. CONCLUSIONS: LEC is a sensitive indicator of H2O2 concentrations and can evaluate the effect of antioxidants in vitro. It is a continuous, sensitive, and direct measurement of OR production in vivo. LEC is ideal for the evaluation of antioxidant interventions and provides direct evidence that pyruvate acts as an antioxidant while improving myocardial function during reperfusion.

Acridines↗
PubMed1997

The mechanisms of coenzyme Q10 as therapy for myocardial ischemia reperfusion injury.

It has been hypothesized that CoQ10 (CoQ) pretreatment protects myocardium from ischemia reperfusion (I/R) injury by its ability to increase aerobic energy production as well as its activity as an antioxidant. Isolated hearts from rats pretreated with either CoQ 20 mg/kg i.m. and 10 mg/kg i.p. or vehicle 24 and 2 h prior to the experiment, were subjected to 15 min of equilibration (EQ), 25 min of ischemia, and 40 min of reperfusion (RP). Developed pressure, +/-dp/dt, myocardial oxygen consumption, and myocardial aerobic efficiency (DP/MVO2) were measured. 31P NMR spectroscopy was used to determine ATP and PCr concentrations. Lucigenin-enhanced chemiluminescence of the coronary sinus effluent was utilized to determine oxidative stress through the protocol. CoQ pretreatment improved myocardial function after ischemia reperfusion. CoQ pretreatment improved tolerance to myocardial ischemia reperfusion injury by its ability to increase aerobic energy production, and by preserving myocardial aerobic efficiency during reperfusion. Furthermore, the oxidative burst during RP was diminished with CoQ. Similarly it was hypothesized that CoQ protected coronary vascular reactivity after I/R via an antioxidant mechanism. Utilizing a newly developed lyposomal CoQ preparation given i.v. 15 min prior to ischemia, ischemia reperfusion was carried out on Langendorff apparatus as previously described. Just prior to ischemia and after RP, hearts were challenged with bradykinin (BK) and sodium nitroprusside (SNP) and change in coronary flow was measured. CoQ pretreatment protected endothelial-dependent and endothelial-independent vasodilation after I/R. We conclude that CoQ pretreatment protects coronary vascular reactivity after I/R via OH radical scavenger action.

Adenosine Triphosphate↗
PubMed1997

Screening mammography: effect of national guidelines on current physician practice.

PURPOSE: To evaluate the effect of national breast cancer screening guidelines on current physician attitudes toward and practice of screening mammography. MATERIALS AND METHODS: Questionnaire responses from 278 physicians were analyzed. The questionnaire had four sections: general information on physician practice and experience, current use of breast cancer screening, perceptions of screening mammography, and physician awareness of and response to the controversy in breast cancer screening. RESULTS: In women aged 40-49 years, 144 (52%) of 278 physicians performed annual clinical breast examination and screening mammography every 2 years; 57 (21%) favored annual mammography and clinical breast examination. In women aged 50 years and older, 232 (83%) physicians screened patients annually with clinical breast examination and mammography. Two hundred seventeen (78%) physicians were aware of the recommended changes in screening guidelines; 54 (19%) were not aware of the changes. Of those aware of the changes, 56 (26%) changed to the new guidelines, 150 (69%) did not change, and six (3%) modified their practice somewhat. CONCLUSION: Physician practice as regards screening mammography is influenced by national guidelines.

Adult↗
PubMed1997

Should women with implants or a history of treatment for breast cancer be excluded from mammography screening programs?

OBJECTIVE: Our objective was to determine whether it is scientifically justified to require that women with implants or a history of treatment for breast cancer be screened in a diagnostic mammography setting and that they be excluded from mammography screening programs. MATERIALS AND METHODS: The recall rates for women with breast implants or a history of treatment for breast cancer who were screened in a dedicated mammography screening program were compared with those of other women in the screening program. The computerized records for the breast screening program of the Department of Radiology at our institution for January 1, 1990, through December 31, 1995, were reviewed. The recall rates for women who had breast implants and those for women with a history of treatment for breast cancer were compared with the recall rates for the other women who underwent screening. Each recall rate included women who were called back for additional evaluation in addition to those for whom a biopsy was recommended on the basis of the screening study. RESULTS: Of 45,134 screening examinations done during the review period, 43,454 (96%) were for women who had no history of breast cancer or of breast implants; 590 (1%) were for women who had undergone mastectomy; 991 (2%) were for women who had been treated with lumpectomy and irradiation for breast cancer; and 99 (0.2%) were for women with breast implants. Among the 43,454 examinations of women with no history of breast cancer or implants, 3081 examinations (7%) led to interpretations that produced requests for the patient to return for additional evaluation. Thirty-six women who had been treated for breast cancer by mastectomy were recalled (6%). Seventy-five women who had undergone lumpectomy and irradiation for breast cancer were recalled (8%). Five women with breast implants were recalled (5%). Statistically, these rates were not significantly different. CONCLUSION: We find no scientific reason to exclude women who have been treated for breast cancer or who have breast implants from dedicated screening programs.

Breast Implants↗
PubMed1997

Imaging of fallopian tube tumors.

OBJECTIVE: The purposes of this study were to investigate the imaging findings in patients with primary fallopian tube neoplasms and to determine whether specific imaging features favor the preoperative diagnosis of fallopian tube tumors (FTT). MATERIALS AND METHODS: Computerized search of medical records from 1984 to 1994 identified 20 patients with a discharge diagnosis of primary fallopian tube carcinoma. Medical records, imaging studies, and pathology findings were reviewed. Eleven patients had available preoperative imaging. RESULTS: Seventeen of 20 patients with primary FTT had unilateral disease. Of these 17, preoperative imaging was available in nine, showing four solid adnexal masses, four complex cystic adnexal masses, and one normal adnexa. The preoperative imaging of these nine patients included six sonographic and five CT studies. Three patients with primary FTT had bilateral tumors, and preoperative imaging was available for two patients: Two sonographic studies and one CT study showed one complex cystic adnexal mass and three normal adnexa. CONCLUSION: Primary FTT commonly presents as an adnexal mass on preoperative imaging and mimics other pelvic malignancies, especially ovarian carcinoma. Making a specific preoperative diagnosis is difficult; however, because primary FTT is unlikely to be confused with a benign process, delay in diagnosis is rare.

Adult↗
PubMed1996

Effects of vesnarinone, a novel orally active inotropic agent with an immunosuppressive action, on experimental cardiac transplantation in rats.

BACKGROUND: Vesnarinone (VES) has been used for treatment of patients with congestive heart failure. In addition to inotropic effects, it seems to have immunosuppressive action. We tested the hypothesis that VES suppresses graft rejection, inotropic dysfunction caused by early rejection, and chronic coronary obstruction in a heterotopic rat cardiac transplantation model. METHODS: (1) To study acute rejection, hearts from Lewis-Brown Norway (LBN) rats were transplanted into Lewis rats, which were treated with or without VES (50 or 100 mg/kg/day orally). (2) In a functional study, LBN hearts with or without VES (100 mg/kg/ day) were isolated and perfused on day 3 after transplantation to assess inotropic response to isoproterenol (3 x 10(-8) M). (3) To study chronic rejection, Lewis hearts were transplanted into Fisher 344 rats, which were treated with or without VES (50 mg/kg/day) for 90 days. Coronary obstructive disease was assessed by morphometric analysis. There were five to six animals in each group. RESULTS: (1) VES (100 mg/kg/day) prolonged LBN heart survival (11.7 +/- 0.7 vs. 9.6 +/- 0.7 days in control; P < 0.05). (2) Left ventricular developed pressure was depressed in transplanted hearts regardless of VES treatment (84 +/- 12, 90 +/- 8 vs. 144 +/- 16 mmHg in untransplanted hearts; P < 0.01). The developed pressure after administration of isoproterenol in VES-treated hearts (184 +/- 20 mmHg) was higher than transplanted hearts without VES (118 +/- 16 mmHg; P < 0.05), and similar to untransplanted hearts (203 +/- 27 mmHg; P = NS). (3) Transplanted hearts treated with or without VES showed similar grades of rejection (2.0 +/- 0.3 vs. 2.6 +/- 0.2; P = NS), intimal area (6,996 +/- 3,186 vs. 13,441 +/- 5,165 microns2; NS), and coronary luminal obstruction (45 +/- 16% vs. 67 +/- 14%; NS). CONCLUSIONS: VES produces mild prolongation in survival of rat heart grafts, but has no significant effect on chronic graft atherosclerosis. VES preserves the positive inotropic effects of isoproterenol that are otherwise deteriorated by early acute rejection.

Acute Disease↗
PubMed1996

Reversible injury: creatinine kinase recovery restores bioenergetics and function.

In postischemia hearts, cytoplasmic creatinine kinase (CK) inactivation resulting from toxic oxygen metabolite injury may lead to bioenergetic and mechanical dysfunction. This study determines the relationship between CK activity, mechanical function, and bioenergetics during reperfusion (RP) after a reversible ischemic injury. Rat hearts pretreated after 12 hr without (CTRL) or with myristic acid (MA) underwent 10 min global, 37 degrees C ischemia followed by 10 or 40 min RP while developed pressure (DP) was monitored. Catalase and CK were assayed at preischemia. CK was also assayed at end ischemia and 10 and 40 min RP. 31 P nuclear magnetic resonance spectra assessed changes in phosphocreatinine (PCr) and adenosine triphosphate (ATP) concentration. Preischemic DP was 95 +/- 5 mm Hg. CTRL DP returned to 84 +/- 3 by RP10 and 88 +/- 6 by RP40 while MA hearts recovered fully by RP10 (90 +/- 2). Preischemic catalase activity was significantly increased in MA hearts (1217 +/- 36 U/g left ventricular tissue (LV) vs 1007 +/- 40 U/g LV, P < 0.01, MA vs CTRL). CTRL CK activity fell from 1870 +/- 75 to 1103 +/- 11 U/g LV at RP10, but rose to 1272 +/- 13 by RP40 (P < 0.01, RP10 vs RP40). MA hearts lost no CK activity during RP. By RP10, CTRL PCr/ATP ratio was elevated to 2.2 +/- 0.2 (P < 0.001) from a preischemic level of 1.7 +/- 0.4 and normalized by RP40, while MA hearts had a normal PCr/ATP throughout RP. Reversible RP injury transiently depresses mechanical function. Cytoplasmic CK damage during RP impairs PCr utilization, leading to a PCr overshoot. Functional recovery and metabolic recovery follow return of CK activity. Increased endogenous catalase preserves CK during RP, resulting in normal function and bioenergetics.

Adenosine Triphosphate↗
PubMed1996

Ischemic preconditioning decreases oxidative stress during reperfusion: a chemiluminescence study.

The mechanism responsible for ischemic preconditioning (IPC) is still unknown but may involve the induction of antioxidant enzymes decreasing oxidative stress during subsequent periods of ischemia (I) and reperfusion (RP). The purpose of this study was to determine whether, in fact, an antioxidant mechanism is involved in the protection afforded by IPC. Lucigenin-enhanced chemiluminescence (LEC), a direct, continuous, nondestructive, on-line method was used to monitor the net amount of free oxygen radicals (FOR) produced during perfusion of rat hearts. Isolated rat hearts were perfused inside a chemiluminescence chamber with lucigenin (1 x 10(-5) M) and subjected to either: (a) 80 min of equilibration (EQ80 group, n = 6), (b) 15 min of EQ, 2 min of IPC, 10 min of reequilibration (REQ), 25 min of I, and 28 min of RP (IPC group, n = 8), or (c) 27 min of EQ, 25 min of I, and 28 min of RP (CTRL, n = 7). Chemiluminescence was measured as counts per minute (cpm) and expressed as %EQ15 (mean +/- SEM). Paired and nonpaired t tests were used for statistical evaluation. EQ80 showed no changes in oxidative stress throughout perfusion (4.5 +/- 0.2 x 10(3) cpm at EQ15 vs 5.1 +/- 0.5 x 10(3) cpm at EQ80, P = NS). During REQ (after IPC) there was a surge of chemiluminescence in IPC hearts compared with CTRL (130 +/- 8% vs 108 +/- 4%, P < 0.05). During reperfusion there was a surge of chemiluminescence in CTRL hearts that was diminished in the IPC hearts (550 +/- 50% vs 380 +/- 50% in IPC, P < 0.05). We conclude that: (1) IPC induces an oxidative stress generating FOR during REQ, (2) IPC decreases the initial FOR burst during RP. We speculate that IPC increases cellular antioxidant defenses which result in decreased oxidative stress during early RP.

Acridines↗