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Biomedical subjects

B G Haffty

Publications and source records attributed to B G Haffty.

At least 91 records · Page 5Linked to original sources
PubMed1982

Effect of oral propranolol on left ventricular performance in patients with ischemic heart disease. Ear densitographic study during uninterrupted treadmill exercise.

The effect of oral propranolol on left ventricular performance during early upright exercise was evaluated by ear densitography in patients with arteriographic coronary artery disease (CAD). Measurements of systolic time intervals differentiated 10 unmedicated patients with CAD (group 1) and 15 patients with CAD taking propranolol (group 3). The patients in group 3 had less shortening of preejection period at 1 minute and 4 minutes of exercise than group 1 patients (p less than 0.001 and p less than 0.005, respectively), with propranolol appearing to prevent the abnormal shortening of preejection period seen in the unmedicated group. Group 3 patients, in contrast to group 1 patients, showed reduction of heart rate and heart rate-blood pressure product both at rest and during exercise. Furthermore, PEP/LVET and percentage change in PEP/LVET from control responses were similar to those of subjects free of CAD (group 2). These results indicate that propranolol effects a favorable change in LV performance by postponing early exhaustion of cardiac reserve, despite significant CAD. There was relatively large overlap in percentage change in PEP/LVET from control between group 2 and group 3 in contrast to the clear separation among unmedicated patients. Thus, the excellent diagnostic accuracy of systolic time intervals recorded during exercise is greatly reduced by beta-adrenoceptor blockade.

Administration, Oral↗
PubMed1981

Elucidation of physiologic lengthening of left ventricular ejection time during early upright exercise.

To elucidate the relationship between heart rate (HR) and left ventricular ejection time (LVET) during early exercise, 30 patients with chest pain were studied at 1 (1') and 4 minutes (4'). Mean results for control leads to 1' exercise: HR 79 to 105 beats per minute, LVET 247 to 260 msec. Thus instead of shortening as predicted by the HR change at 1' of exercise, LVET rose significantly (p less than 0.001). Subsequently LVET fell as HR continued rising, and by 4' had fallen toward control level. This phenomenon is comparable to the paradoxical decline in LVET as HR decreases early post-exercise and is comparably explained by transiently disproportionate change in determinants of LVET, stroke volume, and ejection rate. Absence of difference in response of exercise-positive (ST depression greater than or equal to 1 mm) and exercise-negative patients, also supports this initial paradoxical lengthening in LVET as a physiologic response.

Adult↗
PubMed1981

Noninvasive assessment of left ventricular performance in patients with ischemic heart disease: ear densitographic study during uninterrupted treadmill exercise.

Among 738 consecutive patients with chest pain referred for exercise testing, only 17 men fulfilled strict criteria for this pilot study: (1) achievement of at least 90 percent of age-predicted maximal heart rate or electrocardiographic criteria for a positive test; (2) subsequent coronary angiography; (3) exclusion of prior heart disease; and (4) absence of medication. Measurements of systolic time intervals obtained with ear densitography during early exercise differentiated 10 patients with coronary artery disease (Group 1) from 17 men (7 patients plus 10 normal volunteers) with normal coronary arteries (Group 2). Despite nearly identical heart rate and blood pressure responses in both groups, men in Group 1 had a significantly greater reduction of preejection period (PEP) at 1 minute and 4 minutes as well as a greater decrease in PEP/LVET (left ventricular ejection time) ratio. Differences were most significant when expressed as percent change of PEP/LVET ratio from control value (p less than 0.001 at both 1 minute and 4 minutes). After 4 minutes, men in Group 1 had no further decrease in PEP/LVET ratio and in 8 of the 10 men PEP/LVET ratio then increased to peak exercise. By contrast, PEP/LVET ratio continued to decrease to peak exercise in men in Group 2. The early floor in PEP/LVET ratio in Group 1 represents limited functional reserve and the subsequent increase suggests functional deterioration. Thus, densitographic systolic time interval measurements during uninterrupted exercise in unmedicated subjects appear to improve the sensitivity and specificity of the conventional treadmill test.

Adult↗
PubMed1980

Responses of peak ear-pulse derivative to changing left ventricular function.

The ear densitograph displacement pulse derivative (dD/dtear) is the analog of the arterial pressure derivative (dP/dt) and behaves comparably under a variety of cardiocirculatory challenges. Technical reliability and uniform application of the transducer are advantages that make it ideal for intrasubject monitoring. With atrial fibrillation as a model of functional variability in eight subjects, peak dD/dtear (P) tracked echocardiographic stroke volume, ejection fraction, ejection rate, and velocity of circumferential fiber shortening quite closely with the exception of some values in three subjects, two of whom had mitral regurgitation and one paradoxic septal movement. In all subjects, P showed good to excellent correlations with cycle length, preejection period (PEP), LVET (left ventricular ejection time), and PEP/LVET. The method appears to be ideally suited to intrasubject monitoring for changing ventricular function.

Adolescent↗
PubMed1979

Cardiac responses to impulse exercise and recovery: systolic time intervals.

Exercise responses depend on work load and its pattern of delivery. Administering a very brief ("impulse") load aims to elicit significant responses through biologic sensitivity to rate - rather than degree - of change. Electrocardiograms, systolic time intervals (STI) and heart rate (HR) were recorded continuously in 10 normal subjects during and after brief (20-sec) bicycle exercise at 50, 100 and 150 W. The purpose of this protocol was to identify a low load impulse-type exercise challenge which would be optimal in terms of (a) reproduction of the time course of exercise changes produced by longer duration (steady-state) exercise, (b) rapid achievement of quantitative responses reaching some or all of the steady-state changes at comparable work load, and (c) absence of ST changes in normal subjects. The onset of exercise produced the greatest rates of change. Directional changes and time course of all measurements paralleled those of steady-state exercise and recovery at the same loads: HR, ejection time index (ETI) and corrected ejection time (ETc) increased sharply; preejection period (PEP) and PEP/LVET fell sharply. Ejection time (LVET), stable through most of exercise, "paradoxically" decreased for up to 15 sec of recovery despite decreasing heart rates. For all measurements, restitution to control levels was complete by one minute of recovery.

Adult↗
PubMed1978

Cardiac response during uninterrupted treadmill exercise and recovery: measurement by systolic time intervals.

In 12 normal subjects, use of ear densitography permitted measurement of systolic time intervals (STI) during uninterrupted treadmill exercise to over 90 percent maximal heart rate on a modified Bruce protocol. Results for control (sitting leads to standing) leads to end-exercise at 18 minutes leads to 10 minutes' sitting recovery were--heart rate (HR): (77 leads to 861 leads to 171 leads to 98 beats per minute; preejection period (PEP): (106 leads to 111) leads to 49 leads to 110 msec; ejection time index (ETI) (351 leads to 330) leads to 380 leads to 366 msec; PEP/LVET (0.42 leads to 0.49) leads to 0.29 leads to 0.45. Heart rate increased steadily to 18 minutes. In contrast, the PEP/LVET decrease was almost complete by three minutes and both ETI and PEP responses were bimodal with respective plateaus between three and six minutes and three and nine minutes. All STI and HR curves showed rapid restitution during early recovery. The changes during treadmill exercise were numerically comparable to those during bicycle exercise at a common heart rate. The results indicate that it is technically feasible to measure systolic time intervals with precision during uninterrupted treadmill exercise; responses to treadmill exercise were in the direction expected and quantitatively comparable to bicycle exercise at comparable stress level. These obervations provide the technical and physiologic bases for applying this method in clinical treadmill exercise testing.

Adult↗
PubMedDate not supplied

Bioavailability of organic nitrates: a comparison of methods for evaluating plethysmographic responses.

Erythrityl tetranitrate, a long-acting organic nitrate, was compared with isosorbide dinitrate in a double-blind, placebo-controlled complete crossover study in 15 healthy male volunteers. A digital plethysmogram and ear densitogram were used to assess the physiologic response to these two sublingual nitrates, with the intensity and duration of drug effect calculated by differences in diastolic amplitude intensity before and after drug administration. Both 5 mg sublingual erythrityl tetranitrate and 5 mg isosorbide dinitrate produced significant increases in diastolic amplitude intensity for up to 3 hours. The erythrityl tetranitrate peak effect was less than that of the isosorbide dinitrate, but the incidence of headaches was also less. The ear densitogram was found to be an effective means of assessing the diastolic amplitude intensity changes.

Adult↗
PubMedDate not supplied

Erythrityl tetranitrate compared with isosorbide dinitrate. Effects on systolic time intervals and nitrate modification of effects of food.

The pharmacologic effects of erythrityl tetranitrate (ETN) and isosorbide dinitrate (ISDN) were compared to placebo using systolic time intervals (STI) in a randomized, double-blind study in 15 fasted male volunteers. Sublingual doses of ETN 5 mg, ISDN 5 mg, and placebo were administered to each volunteer at weekly intervals, and measurements of heart rate and STI [pre-ejection period (PEP), left ventricular ejection time (LVET), and PEP/LVET ratio] were made serially for up to 6 hours after each dose. STI were determined using ear densitography. Evaluation of the pharmacologic effects of ETN and ISDN were based on placebo-corrected changes from baseline values. Ejection time index (ETI) [LVET corrected for heart rate] was shortened, but the changes were not statistically significant for either drug. However, after ETN and ISDN, statistically significant (p less than 0.05) changes in PEP and PEP/LVET ratio were demonstrated for up to 240 minutes after dosing. Unexpected marked changes in the baseline corrected PEP/LVET ratio were observed following food at 4 hours after dosing. This suggests increased inotropy during the postprandial period.

Adult↗
PubMedDate not supplied

The location of contralateral breast cancers after radiation therapy.

Radiation therapy following conservative surgery results in scattered radiation to the contralateral breast, with higher doses to the medial breast and lower doses laterally. The purpose of the current study is to determine whether the location of contralateral breast cancers developing following breast conserving surgery and radiation is indicative of radiation-induced malignancies. The charts of 1,755 patients treated with conservative surgery and radiation therapy between 1970 and 1998 were reviewed. Fifty-nine patients who developed a contralateral malignancy following conservative surgery and radiation therapy and who had complete information and documentation of the location of the second lesion served as the primary focus of the current study. The location of the contralateral malignancy was compared with the location of the primary tumors of the overall patient population. The location of breast cancers developing in the contralateral breast following breast conserving therapy and radiation was not consistent with radiation-induced malignancies. Specifically, there was not a preponderance of medially located tumors in patients developing contralateral breast cancers following radiation. There was a slight excess of central lesions that cannot be explained by higher doses of radiation. The location of breast cancers in the contralateral breast following conservative surgery and radiation is not indicative of radiation-induced lesions. These data should be reassuring to women considering breast conserving surgery and radiation.

Breast Neoplasms↗
PubMedDate not supplied

Adjuvant sequential dose-dense doxorubicin, paclitaxel, and cyclophosphamide (ATC) for high-risk breast cancer is feasible in the community setting.

PURPOSE: This study evaluated the feasibility, when given in the community, of dose-dense, sequential ATC (doxorubicin, paclitaxel, cyclophosphamide) as adjuvant therapy for breast cancer with four or more metastatic axillary lymph nodes. PATIENTS AND METHODS: Patients were recruited after definitive breast cancer surgery if four or more axillary nodes were involved by metastatic cancer and if distant metastases were not present on computed tomographic scan or bone scan. Forty patients received doxorubicin, 90 mg/m2 every 14 days for three cycles; paclitaxel, 250 mg/m2 every 14 days for three cycles; and cyclophosphamide, 3 g/m2 every 14 days for three cycles with filgrastim support. Chemotherapy was administered by the referring physician. RESULTS: Mean dose intensity was 99% for doxorubicin, 96% for paclitaxel, and 99% for cyclophosphamide. Grade 3 toxicities included mucositis (13%), nausea/vomiting (10%), neuropathy (13%), and myalgia/arthralgia (10%). Thirteen patients had neutropenic fever. One patient developed acute leukemia. Three relapses have occurred. Ninety percent of patients are alive and disease-free at a median follow-up of 24 months. DISCUSSION: ATC can be administered in the community at full doses with acceptable toxicity. Preliminary efficacy data suggest that this high-dose, intensively scheduled regimen warrants comparison with standard therapy for high-risk patients.

Adult↗
PubMedDate not supplied

Radiation therapy with hyperbaric oxygen at 4 atmospheres pressure in the management of squamous cell carcinoma of the head and neck: results of a randomized clinical trial.

PURPOSE: The purpose of this study was to present the results of a randomized trial evaluating HBO-4 in combination with hypofractionated radiation therapy in patients with locally advanced squamous cell carcinoma of the head and neck (SCCHN). METHODS AND MATERIALS: Between April 1974 and December 1975, 48 patients with locally advanced unresected SCCHN, referred for primary radiation therapy, were randomized to radiation delivered in air in two fractions of 12.65 Gy over 21 days to a total of 25.30 Gy (air, n = 25); or radiation under HBO-4 in two fractions of 11.50 Gy over 21 days to at total of 23.00 Gy (HBO-4, n = 23). The HBO-4 was administered under general anesthesia to minimize patient discomfort and potential problems with seizures associated with rapid compression to 4 atmospheres. Patients were monitored regularly by the radiation oncologists for toxicity, response, local control, and survival. The original hospital records, radiation records, and hyperbaric treatment logs were recently reviewed, and all data were entered onto a computerized database for the current analysis. The results of this trial have not previously been published. RESULTS: The air and HBO-4 arms were evenly matched with respect to age, sex, performance status, hemoglobin level, primary site, and stage of disease. Acute toxicities were acceptable with no significant differences between the two treatment arms. A trend toward excess severe late complications were noted in the hyperbaric arm (12 vs 7). There was a highly significant difference in complete clinical responses between the two arms, with 21/25 in complete dinical responses in the HBO-4 arm compared with 13/25 in complete clinical responses in the air arm, and a statistically insignificant trend toward improved 5-year local control in the HBO-4 arm (29% vs 16%). There were no significant differences between the two arms with respect to 5-year survival, distant metastasis, or second primary tumors. CONCLUSIONS: Long-term outcome from this historical randomized trial demonstrate substantial improvements in response rate with the use of HBO-4. The hypofractionation scheme used in the trial resulted in relatively low local control and high complication rates in this group of patients with very advanced SCCHN. However, these results support the theory that radioresistant hypoxic cells limit the radiocurability of SCCHN. Further investigations addressing the hypoxic cell problem with hypoxic cytotoxins or hypoxic cell sensitizers in combination with radiation therapy using more conventional fractionation schemes are warranted.

Atmospheric Pressure↗
PubMedDate not supplied

Negative margin status improves local control in conservatively managed breast cancer patients.

OBJECTIVE: The purpose of this study was to determine the impact of final pathologic margin status on breast relapse-free survival, distant metastasis-free survival, and overall survival in patients undergoing conservative surgery and radiation therapy for invasive breast cancer. MATERIALS AND METHODS: Between January 1970 and December 1990, 984 patients underwent conservative surgery and radiation therapy at our institution as treatment for invasive breast cancer. After lumpectomy, patients were given radiation therapy to the intact breast with or without treatment to regional nodes with the routine use of electron boost to a total median tumor bed dose of 64 Gy. Pathology reports were available for review in 871 patients. Re-excision was carried out in 294 of these patients. For this analysis, patients were divided into four groups based on final pathologic margin status: negative (n = 278), dose (typically within 2 mm, n = 47), positive (n = 55), or indeterminate (n = 491). RESULTS: There were no significant differences between the groups with respect to age, histology, estrogen and progesterone receptor status, tumor location, or total radiation dose. Patients with negative margins were more likely than those with positive margins to have T1 mammographically detected lesions, to have negative nodal status, and to have undergone re-excision. Patients with positive margins were more likely to receive adjuvant chemotherapy or hormone therapy (P = 0.001). As of July 1998, with a median follow-up of 13 years, the median breast relapse-free survival, distant metastasis-free survival, and overall survival rates at 10 years for the entire cohort of patients were 86%, 81%, and 76%, respectively. Breast relapse-free survival at 10 years was 98% for patients with negative margins versus 98% for those with close margins versus 83% for those with positive margins versus 82% for those with indeterminate margins. There were no significant differences in breast relapse-free survival between patients with negative and dose margins or between patients with positive and indeterminate margins. Although the negative margin status also conferred an overall survival and distant metastasis-free survival advantage, this difference is confounded by the earlier stage of disease in these patients, and margin status did not influence overall survival in multivariate analysis. CONCLUSION: In patients undergoing conservative management of breast cancer, negative margin status significantly improves breast relapse-free survival. Close margins appear equivalent to negative margins, and indeterminate margins appear equivalent to positive margins. Adjuvant chemotherapy or hormone therapy did not counteract the adverse impact of positive margin status. Re-excision to obtain dear surgical margins is recommended, even if a radiation boost or adjuvant systemic therapy is planned.

Breast Neoplasms↗
PubMedDate not supplied

Breast-conserving therapy in the setting of collagen vascular disease.

BACKGROUND: It is unclear whether the presence of collagen vascular disease should be considered a contraindication to irradiation. This study was undertaken to determine whether women with pre-existing collagen vascular disease have an increased incidence of complications after breast-conserving therapy. METHODS AND MATERIALS: A cohort of 36 patients with documented collagen vascular disease was conservatively treated for early-stage breast cancer between 1975 and 1998. All of these patients were treated with conventional radiation therapy to a total medium dose of 64 Gy. Seventeen had rheumatoid arthritis; four, scleroderma; four, Raynaud's phenomenon; five, lupus erythematosus; two, Sjögren's disease; and four, polymyositis. Each of these patients was matched to two control patients without a history of collagen vascular disease on the basis of age, radiation therapytechnique, chemotherapy or hormone therapy use, tumor histology, and date of treatment. Acute and late complications were assessed using a six-point scale from the toxicity criteria of the Radiation Therapy Oncology Group and the European Organization for Research and Treatment of Cancer. The scoring system for both acute and late reactions ranged from 0 (no change over baseline) to 5 (radiation led to death). For the purpose of statistical analysis, patients were classified as having a significant complication if they had a score of 3 or greater. RESULTS: With a median clinical follow-up time of 12.5 years (range, 3.0-22.5 years), no significant difference was detected between the collagen vascular disease and control groups with respect to acute complications (14% vs 8%). With respect to late complications, a significant difference was observed (17% vs 3%) between the two groups. However, when patients in the collagen vascular disease group were analyzed by specific disease, this significance disappeared in all but the scleroderma group. CONCLUSIONS: Patients with scleroderma have a statistically significant increased incidence of radiation therapy complications after breast-conserving surgery and radiation therapy. The presence of other collagen vascular diseases should not be considered a contraindication for this treatment modality.

Adult↗
PubMedDate not supplied

Noninvasive ambulatory monitoring of physiologic data: recording systolic time intervals.

Adding physiologic data to ambulatory electrocardiographic monitoring data yields information with great potential for diagnostic and therapeutic use. The ear densitogram's stability, demonstrated during exercise and under laboratory conditions, indicates its applicability to ambulatory monitoring as a source of systolic time intervals. Circuitry has been developed to feed the output of an ear densitogram pickup into one channel of a two-channel Holter monitor. Baseline studies in different postures are used to establish pulse transmission time, which permits the ear densitogram pulse to be used as a delayed aortic pulse in measuring systolic time interval. Feasibility and field studies have shown that systolic time intervals can be precisely determined by this method.

Activities of Daily Living↗
PubMedDate not supplied

Mammographically detected, clinically occult ductal carcinoma in situ treated with breast-conserving surgery and definitive breast irradiation.

PURPOSE: Ductal carcinoma in situ (DCIS) is increasingly detected as a nonpalpable lesion on mammographic screening performed for the early detection of breast cancer. Because of the growing incidence of mammographically detected DCIS, the present study was undertaken to determine the outcome of treatment of nonpalpable, mammographically detected intraductal carcinoma of the breast using breast-conserving surgery and definitive breast irradiation. MATERIALS AND METHODS: An analysis was performed of 110 women who presented with unilateral, nonpalpable, mammographically detected intraductal carcinoma of the breast and who were treated with breast-conserving surgery and definitive breast irradiation at 10 institutions in Europe and the United States. In all patients, complete gross excision of the primary tumor was performed, and breast irradiation was delivered with definitive intent. When performed, pathologic axillary lymph node staging was node negative (n=29). The median follow-up time was 9.3 years. RESULTS: The 10-year actuarial overall survival rate was 93%, and the 10-year actuarial cause-specific survival rate was 96%. The 10-year actuarial rate of freedom from distant metastases was 96%. There were 15 local recurrences in the treated breast. The actuarial rate of local failure was 7% at 5 years and 14% at 10 years. The histology of the local recurrence was intraductal carcinoma in 9 cases and invasive ductal carcinoma (with or without associated intraductal carcinoma) in 6 cases. The median time to local recurrence was 5.0 years (mean, 5.4; range, 2.1-15.2). With a median follow-up time of 4.4 years after salvage treatment, 14 of the 15 patients with local recurrence were alive without evidence of disease at the time of last follow-up examination. The crude incidence of local recurrence was 7% (3/42) when the final pathology margin of tumor excision was negative, 29% (5/17) when the margin was close or positive, and 14% (7/51) when the margin was unknown. There was no difference in the rate of local recurrence based on pathologic characteristics of the primary tumor. DISCUSSION: Results from the present study demonstrate high rates of overall survival, cause-specific survival, and freedom from distant metastases at 10 years following the treatment of nonpalpable, mammographically detected DCIS of the breast using breast-conserving surgery and definitive breast irradiation. Local recurrences within the treated breast were detected early and were treated with salvage for cure. These results support the initial treatment of nonpalpable, mammographically detected DCIS of the breast using breast-conserving surgery and definitive breast irradiation. Improvements in patient selection have the potential to reduce the risk of local recurrence.

Adult↗