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Biomedical subjects

J Heckman

Publications and source records attributed to J Heckman.

10 recordsLinked to original sources
PubMed2001

Effects of cilostazol on resting ankle pressures and exercise-induced ischemia in patients with intermittent claudication.

During exercise, patients with intermittent claudication (IC) have decreased limb arterial blood pressure that recovers during rest. A novel method for assessing dynamic recovery of function is measurement of the hemodynamic response after exercise. Cilostazol (Pletal), a new agent for the treatment of IC, increases walking distance and may decrease ischemic burden. The objective of this study was to assess the effect of cilostazol versus placebo on hemodynamic measurements after exercise-induced ischemia in patients with IC. Two double-blind, placebo-controlled studies with similar inclusion/exclusion criteria and duration (24 weeks) were pooled. Patients walked on a treadmill at 2.0 miles/h (3.2 km/h) on a 12.5% grade until the claudication-limited maximal walking distance (MWD) was reached. Anterior and posterior tibial pressures were measured with Doppler ultrasound at baseline and at 1, 5, and 9 min during recovery. Area under the curve (AUC), a measure of the time course of recovery of systolic pressure after exercise-induced ischemia, and ankle-brachial index (ABI) were calculated and compared using analysis of variance (ANOVA). All three treatment groups (308 patients randomized to cilostazol 100 mg bid, 303 to cilostazol 50 mg bid, and 299 to placebo) had similar baseline characteristics. Mean post-exercise AUC for cilostazol 100 mg and 50 mg bid versus placebo increased by 0.31 (p = 0.001) and 0.26 (p = 0.004), respectively. Mean resting ABI increased by 0.03 (p = 0.0039) and 0.04 (p = 0.0001) in the cilostazol 100 mg and 50 mg bid groups, respectively. In conclusion, following 24 weeks of treatment, cilostazol increased the ABI at rest and improved the recovery time of ankle pressures post-exercise.

Aged↗
PubMed1998

Effect of cilostazol on walking distances in patients with intermittent claudication caused by peripheral vascular disease.

PURPOSE: This study evaluated the effects of cilostazol on walking distances in patients with intermittent claudication (IC) caused by peripheral arterial occlusive disease. METHODS: The study was a multicenter, randomized, double-blind, placebo-controlled trial. Two hundred thirty-nine patients with IC were randomly assigned to receive cilostazol (100 mg b.i.d.) or a placebo for 16 weeks. All patients underwent serial, variable-grade, constant-speed treadmill testing. Absolute claudication distance (ACD), assessed at the end of the 12-hour dosing interval (trough), was the primary end point. Secondary end points included ACD assessed 3 to 4 hours after dosing (peak) and initial claudication distances (trough and peak). Functional status measures, including the Medical Outcomes Scale (SF-36) and Walking Impairment Questionnaire, were used to assess subjective changes over the 16-week treatment period. Ankle-brachial indexes were calculated from Doppler-measured systolic pressures at every visit with treadmill testing. RESULTS: Patients treated with cilostazol demonstrated significant improvements over the placebo patients in ACD at all three time points tested after baseline (weeks 8, 12, and 16). Peak treadmill testing at weeks 8 and 12 also showed significant improvement in walking distances for cilostazol-treated patients over placebo-treated patients. At week 16, patients in the cilostazol group had a 96.4-meter (47%) increase in ACD compared with 31.4 meters (12.9%) for the placebo group (p < 0.001). In the SF-36, significant improvement was observed in the physical component subscale and the composite physical component score. In the Walking Impairment Questionnaire, improvements were significant in patient reports of walking speed and specific measures of walking difficulty. Ankle-brachial indexes improved in the cilostazol group (0.64 +/- 0.02 to 0.70 +/- 0.02) compared with the placebo group (0.68 +/- 0.02 to 0.69 +/- 0.02) (p < 0.0125). The most frequent adverse events were headache, abnormal stools (e.g. loose stools), diarrhea, and dizziness. CONCLUSIONS: Cilostazol significantly increased ACD at all measured time points and initial claudication distances at most time points. This agent may represent a new treatment option for patients with intermittent claudication.

Cilostazol↗
PubMed1998

Effect of the novel antiplatelet agent cilostazol on plasma lipoproteins in patients with intermittent claudication.

Cilostazol is an antiplatelet agent and vasodilator marketed in Japan for treatment of ischemic symptoms of peripheral vascular disease. It is currently being evaluated in the United States for treatment of symptomatic intermittent claudication (IC). Cilostazol has been shown to improve walking distance in patients with IC. In addition to its reported vasodilator and antiplatelet effects, cilostazol has been proposed to have beneficial effects on plasma lipoproteins. We examined the effect of cilostazol versus placebo on plasma lipoproteins in 189 patients with IC. After 12 weeks of therapy with 100 mg cilostazol BID, plasma triglycerides decreased 15% (P<0.001). Cilostazol also increased plasma high density lipoprotein cholesterol (HDL-C) (10%) and apolipoprotein (apo) A1 (5.7%) significantly (P<0.001 and P<0.01, respectively). Both HDL3 and HDL2 subfractions were increased by cilostazol; however, the greatest percentage increase was observed in HDL2. Individuals with baseline hypertriglyceridemia (>140 mg/dL) experienced the greatest changes in both HDL-C and triglycerides with cilostazol treatment. In that subset of patients, HDL-C was increased 12.2% and triglycerides were decreased 23%. With cilostazol, there was a trend (3%) toward decreased apoB as well as increased apoA1, resulting in a significant (9.8%, P<0.002) increase in the apoA1 to apoB ratio. Low density lipoprotein cholesterol and lipoprotein(a) concentrations were unaffected. Cilostazol treatment resulted in a 35% increase in treadmill walking time (P=0.0015) and a 9.03% increase in ankle-brachial index (P<0.001). These results indicate that in addition to improving the symptoms of IC, cilostazol also favorably modifies plasma lipoproteins in patients with peripheral arterial disease. The mechanism of this effect is currently unknown.

Adrenergic beta-Antagonists↗
PubMed1998

Quantitative bronchoscopic assessment of airway collapsibility in newborn lamb tracheae.

To date, quantitative studies of the inherent characteristics of the developing airway wall have required excision of an airway segment or surgical creation of an isolated segment. We hypothesized that airway wall characteristics, at various collapsing pressures, and attendant changes in stiffness after smooth muscle stimulation could be quantitated bronchoscopically from airway pressure-area relationships. Neonatal lamb tracheal segments (n = 12) were suspended over hollow mounts, in a buffer-filled chamber, and subjected to a range (0 to -4.0 kPa) of pressures to determine wall stiffness under collapsing forces before and after stimulation of the trachealis with methacholine. Luminal images were recorded through a 3.6-mm flexible bronchoscope under the same conditions, subsequently corrected for distortion, and a cross-sectional area was quantitated. Both pressure-volume and pressure-area relationships detected significant changes in airway wall stiffness after methacholine administration (p < 0.002), and the magnitude of change was similar between methods. These data suggest that quantitative flexible bronchoscopy can be used clinically in the intact airway to assess wall stiffness.

Animals↗
PubMed1981

Highly conserved GC-rich palindromic DNA sequences flank tRNA genes in Neurospora crassa mitochondria.

In sequencing a 2200 bp region of the Neurospora crassa mitochondrial DNA encoding the 3' end of the large rRNA gene and a cluster of six tRNA genes, we have found that the tRNA genes are flanked by highly conserved GC-rich palindromic DNA sequences. An 18 bp long core sequence, 5'-CC CTGCAG TA CTGCAG GG-3', containing two closely spaced Pst I sites, is common to all these palindromic sequences. Each of the eight Pst I sites mapped in the 2200 bp region consists of two closely spaced Pst I sites; thus this 2200 bp long segment actually contains 16 Pst I sites. Between 5-10% of the N. crassa DNA may consist of these GC-rich palindromic sequences that include the 18 base long core sequence. The same core sequence is present within both the 5' and 3' side of the intervening sequence of the large rRNA gene, close to, but not at, the intron-exon boundaries. We discuss probable roles for these sequences in N. crassa mitochondrial function, including their role as signals either in the synthesis or processing (or both) of RNA in the mitochondria.

Base Sequence↗
PubMed1979

The nucleotide sequence of the initiator tRNA from Drosophila melanogaster.

The nucleotide sequence of Drosophila melanogaster methionine tRNAi was determined to be: pA-G-C-A-G-A-G-U-m1G-m2G-C-G-C-A-G-U-G-G-A-A-G-C-G-U-m2G-C-U-G-G-G-C-C-C-A-U-t6A-A-C-C-C-A-G-A-G-m7G-D-m5C-C-C-G-A-G-G-A-U-C-G-m1A-A-A-C-C-U-U-G-C-U-C-U-G-C-U-A-C-C-A(OH). It differs from vertebrate initiator tRNAs in only 6 out of 75 positions.

Animals↗
PubMed1976

Myocardial interaction between the ventricles.

The myocardial interaction between the ventricles was studied using isolated, flow-perfused, paced rabbit hearts beating isovolumically. In general, increasing left ventricular (LV) volume increased right ventricular (RV) diastolic and developed pressures. In particular, with a peak RV volume (RVV), increasing LV volume (LVV) from zero to two-thirds of its peak volume increase RV diastolic pressure by 1.7 mmHg (N=10, P less than 0.001) and RV developed pressure by 1.5 mmHg (N=10,P less than 0.001). For the LV, small RVV caused LV diastolic and developed pressure to increase, while large RVV increased LV diastolic pressure but decreased LV developed pressure. With a LVV held at two-third of peak volume, increasing RVV from zero to its peak volume caused LV diastolic pressure to increase by 2.5 mmHg (N=10,P less than 0.001) and LV developed pressure to decrease by 2.0 mmHg (N=10, P less than 0.001). The position of the interventricular septum correlated with LV diastolic pressure and RV diastolic and developed pressure changes (P less than 0.01). The results demonstrate that the diastolic and developed pressure-volume relationships of either ventricle can be acutely altered by varying the volume of the other ventricle.

Animals↗
PubMed1973

Absence of the sequence G-T-psi-C-G(A)- in several eukaryotic cytoplasmic initiator transfer RNAs.

The nucleotide sequence G-T-Psi-C-G(A)- has previously been found in every tRNA of known sequence that is active in protein biosynthesis. An exception to this generalization is the recently sequenced initiator tRNA from yeast cytoplasm. It is now reported that cytoplasmic initiator tRNAs from wheat germ, rabbit liver, and sheep mammary gland also lack the G-T-Psi-C-G(A)- sequence. Thus: (i) nucleoside composition analyses show the absence of T in all these tRNAs; (ii) analyses of oligonucleotide fragments produced by T1 ribonuclease show the absence not only of the T-Psi-C-G(A)- sequence, but also of U-Psi-C-G(A)- or U-U-C-G(A)- sequences in such digests. The absence of G-T-Psi-C-G(A)- in the eukaryotic cytoplasmic initator tRNAs is, therefore, not simply due to lack of enzymatic modification of U to T.

Adenosine↗