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M J MacDonald

Publications and source records attributed to M J MacDonald.

At least 37 records · Page 2Linked to original sources
PubMed1999

Comparison of femoral blood gases and muscle near-infrared spectroscopy at exercise onset in humans.

We hypothesized that near-infrared spectroscopy (NIRS) measures of hemoglobin and/or myoglobin O2 saturation (IR-SO2) in the vascular bed of exercising muscle would parallel changes in femoral venous O2 saturation (SfvO2) at the onset of leg-kicking exercise in humans. Six healthy subjects performed transitions from rest to 48 +/- 3 (SE)-W two-legged kicking exercise while breathing 14, 21, or 70% inspired O2. IR-SO2 was measured over the vastus lateralis muscle continuously during all tests, and femoral venous and radial artery blood samples were drawn simultaneously during rest and during 5 min of exercise. In all gas-breathing conditions, there was a rapid decrease in both IR-SO2 and SfvO2 at the onset of moderate-intensity leg-kicking exercise. Although SfvO2 remained at low levels throughout exercise, IR-SO2 increased significantly after the first minute of exercise in both normoxia and hyperoxia. Contrary to the hypothesis, these data show that NIRS does not provide a reliable estimate of hemoglobin and/or O2 saturation as reflected by direct femoral vein sampling.

Adult↗
PubMed1998

Regulation of rat pyruvate carboxylase gene expression by alternate promoters during development, in genetically obese rats and in insulin-secreting cells. Multiple transcripts with 5'-end heterogeneity modulate translation.

A previous study on the gene structure of rat pyruvate carboxylase revealed that two tissue-specific promoters are responsible for the production of multiple transcripts with 5'-end heterogeneity (Jitrapakdee, S., Booker, G. W., Cassady, A. I., and Wallace, J. C. (1997) J. Biol. Chem. 272, 20522-20530). Here we report transcription and translation regulation of pyruvate carboxylase (PC) expression during development and in genetically obese rats. The abundance of PC mRNAs was low in fetal liver but increased by 2-4-fold within 7 days after birth, concomitant with an 8-fold increase in the amount of immunoreactive PC and its activity and then decreased during the weaning period. Reverse transcriptase polymerase chain reaction analysis indicated that the proximal promoter was activated during the suckling period and reduced in activity at weaning. In genetically obese Zucker rats, adipose PC was 4-5-fold increased, concomitant with a 5-6-fold increase in mRNA level. Reverse transcriptase-polymerase chain reaction analysis also showed that the proximal promoter was activated in the hyperlipogenic condition. Conversely, transcription of the proximal promoter was not detectable in various liver cell lines, suggesting that this promoter was not functional under cell culture conditions. In rat pancreatic islets and insulinoma cells, only transcripts D and E, generated from the distal promoter of the PC gene, were expressed. Glucose increased PC transcripts from the distal promoter when the insulinoma cells were maintained in 10 mM glucose. We conclude that the proximal promoter of the rat PC gene plays a major role in gluconeogenesis and lipogenesis, whereas the distal promoter is necessary for anaplerosis. In vitro translation and in vivo polysome profile analysis indicated that transcripts C and E were translated with similar translational efficiencies that are substantially greater than that of transcript D, suggesting that 5'-untranslated regions play a role in translational control.

Aging↗
PubMed1998

Cost efficacy of duplex surveillance and prophylactic angioplasty of arteriovenous ePTFE grafts.

Poor patency of arteriovenous ePTFE grafts remains a major clinical problem. Prophylactic balloon angioplasty of stenoses has been claimed to prolong graft patency and has been widely introduced into practice. In this manuscript we report the cost incurred in application of such a program involving graft surveillance and prophylactic angioplasty of ePTFE graft stenoses >50% diameter. All patients in a single dialysis unit with ePTFE bridge grafts were subject to a surveillance duplex ultrasound and those with a perigraft stenosis of >50% then underwent angiography. Those patients confirmed to have a stenosis >50% within the graft, were randomized to prophylactic percutaneous transluminal angioplasty (PTA) versus no intervention (observation). Patients were followed every 3 months with ultrasound and those in the treatment group with recurrent stenosis (>50%) were subject to repeat PTA. The outcome was thrombosis. Relevant charges were considered to be: initial duplex screening of the entire ePTFE dialysis group; professional and technical fees for angiography and angioplasty; follow-up duplex scanning; repeat angioplasty; and costs of lytic therapy for an intraprocedure lysis. In the treatment and observation group the 6-month patencies were 69% +/- 7% and 70% +/- 7%, respectively. Twelve-month patencies for the treatment and observation groups were 51% +/- 6% and 47% +/- 4%. There was no significant difference between these two groups (p = 0.97), with an 80% confidence limit for detection of a difference >20%. Cost for duplex screening of all patients in the dialysis unit with ePTFE grafts was $40,440 (@ $337 each x 120 patients). Total charges for initial angiography was $178. Angioplasty charges were $143,040. Cost of the follow-up duplex ultrasound scanning in the treated group was $32,352. Charges for repeat angiograms in those with recurrent stenoses were $83,682 (professional fee $1733 + $229; technical fee + $820; equipment charges x 32 x 0.94). One patient required urokinase therapy for an occlusion following PTA. The overall charge for treating the 32 patients in the treatment arm of this study was $440,834, there was net improvement in patency. A policy of generic graft surveillance and prophylactic is expensive and does not lead to improved patency. Until an effective intervention is defined by prospective randomized trial, surveillance duplex scanning cannot be justified.

Angioplasty, Balloon↗
PubMed1998

Myocardial distribution of antegrade cold crystalloid and tepid blood cardioplegia.

BACKGROUND: Tepid blood (TB) cardioplegia combines the improved rheologic characteristics and the augmented oxygen and substrate delivery of blood cardioplegia with the advantages of moderate hypothermia. In addition, the intramyocardial distribution of continuous TB cardioplegia may also be better than intermittent cold crystalloid (CC) cardioplegia. We sought to compare the distribution of TB and CC cardioplegia at varying infusion pressures. METHODS: In situ, isolated canine hearts were randomized to antegrade, continuous TB (28 degrees C, n = 8) or intermittent CC (n = 8) cardioplegia infused at 50, 75, and 100 mm Hg. The regional distribution of cardioplegia at each pressure was measured by 15-microm colored microspheres. Cardioplegia distribution was measured from three areas each of the right ventricle (inflow, outflow, and apex) and the left ventricle (anterior, lateral, and posterior). Left ventricular samples were subdivided into subepicardial, midmyocardial, and subendocardial. RESULTS: Delivery of cardioplegia to all areas of the right and left ventricles showed a linear pressure-flow relationship over the range of pressures tested. Right ventricular distribution was two-thirds of that to the left ventricle, and left ventricular subepicardial distribution was approximately one half of subendocardial flow in both groups at all delivery pressures. However, the subendocardial to subepicardial ratio was significantly greater with TB cardioplegia than with CC cardioplegia. Transmural right ventricular cardioplegia flow was comparable in both groups. In contrast, left ventricular distribution of CC cardioplegia was greater than TB cardioplegia at all three pressures tested. CONCLUSIONS: The pressure-flow relationship in both CC and TB cardioplegia is linear in both the right and left ventricular myocardium over clinically applicable delivery pressures. The distribution of cardioplegia to the right ventricle is not altered by increased pressure.

Animals↗
PubMed1998

Local anesthesia for above knee femoropopliteal bypass: an alternative technique to endoluminal bypass grafting.

BACKGROUND: The majority of patients with peripheral vascular disease have associated medical illnesses that contribute to a substantial incidence of perioperative complications. Some of the these complications may be related to the choice of anesthetic used. An ideal anesthetic would provide good analgesia, have few complications associated with its use, including minimizing hemodynamic instability, and provide an adequate surgical environment. MATERIALS AND METHODS: Ten patients with an occluded superficial femoral artery and claudication or rest pain were selected. Eligibility criteria were a non-obese thigh and an above knee popliteal segment of at least 10 cm. Lidocaine local anesthesia with systemic sedation was employed. Above knee femoropopliteal bypasses were performed in all patients. Intraoperative fluid volume, anesthetic dose and perioperative morbidity were recorded. RESULTS: All patients tolerated the procedure well. The operating environment was excellent. Intraoperative fluid requirements were less for patients receiving local anesthesia as compared with a similar group of patients undergoing above knee femoropopliteal bypass receiving regional anesthesia (mean 1750 ml versus 3386 ml). The mean dosage of lidocaine (0.5%) was 367 mg over a mean of 116 min operating time. All patients ambulated within 8 hours. There was no perioperative morbidity, mortality or graft occlusion. CONCLUSION: This technique is easy to perform and further reduces the systemic magnitude of anesthesia, while providing excellent perioperative analgesia and a satisfactory surgical environment. It may be ideal for the high risk patient, as intraoperative fluid volume requirements are reduced. In an era where endoluminal bypass grafting is being increasingly advocated, this technique retains the benefits of bypass grafting while possibly reducing the physiological insult.

Anastomosis, Surgical↗
PubMed1998

Alveolar oxygen uptake and femoral artery blood flow dynamics in upright and supine leg exercise in humans.

We tested the hypothesis that the slower increase in alveolar oxygen uptake (VO2) at the onset of supine, compared with upright, exercise would be accompanied by a slower rate of increase in leg blood flow (LBF). Seven healthy subjects performed transitions from rest to 40-W knee extension exercise in the upright and supine positions. LBF was measured continuously with pulsed and echo Doppler methods, and VO2 was measured breath by breath at the mouth. At rest, a smaller diameter of the femoral artery in the supine position (P < 0. 05) was compensated by a greater mean blood flow velocity (MBV) (P < 0.05) so that LBF was not different in the two positions. At the end of 6 min of exercise, femoral artery diameter was larger in the upright position and there were no differences in VO2, MBV, or LBF between upright and supine positions. The rates of increase of VO2 and LBF in the transition between rest and 40 W exercise, as evaluated by the mean response time (time to 63% of the increase), were slower in the supine [VO2 = 39.7 +/- 3.8 (SE) s, LBF = 27.6 +/- 3.9 s] than in the upright positions (VO2 = 29.3 +/- 3.0 s, LBF = 17.3 +/- 4.0 s; P < 0.05). These data support our hypothesis that slower increases in alveolar VO2 at the onset of exercise in the supine position are accompanied by a slower increase in LBF.

Adult↗
PubMed1997

Hemodialysis access graft stenosis: percutaneous transluminal angioplasty.

Maintenance of dialysis access continues to plague care of the patient with ESRD. Because of the poor outcomes from surgical revision, there is increasing interest in balloon angioplasty as a technique for dilating stenoses in the functioning, but compromised graft. Forty patients treated with percutaneous transluminal angioplasty (PTA), without subsequent intervention, for graft dysfunction were retrospectively studied. Time to thrombosis of the graft was noted. Patency was determined using the Kaplan-Meier technique. Patency following PTA at 1, 6, and 12 months was 76, 27, and 10%. Patency following PTA of arteriovenous graft stenoses results in disappointing medium and long-term patency. Alternate strategies for improving patency of these conduits should be explored.

Angioplasty, Balloon↗
PubMed1997

Time course of brachial artery diameter responses to rhythmic handgrip exercise in humans.

OBJECTIVE: Whether the dimensions of conduit arteries contribute to the time course of change in blood flow during voluntary rhythmic exercise, and the mechanisms governing such a response in humans, are not known. METHODS: The time course of change in the vascular and blood flow dynamics in the brachial artery during the transition between rest and 5 min of rhythmic handgrip exercise was assessed in humans using continuous measures of brachial artery mean blood velocity (MBV; pulsed Doppler), diameter (echo Doppler) and mean arterial pressure (Finapres). The exercise cadence was 1s/1s (Fast) and 1s/2s (Slow) work/rest schedules while supine with the arm positioned above or below the heart. RESULTS: Brachial artery diameter of the active arm was reduced 5% at approximately 10 s following the onset of exercise performed above the heart (P < 0.05), irrespective of work rate, and returned to rest levels by 30 s with no concurrent changes in arterial pressure. By 2 min of the Fast contraction rate exercise, brachial artery diameter of the active arm was greater than rest (P < 0.05) irrespective of arm position. Brachial artery dimensions in the contralateral inactive arm were not altered during exercise (P > 0.05). Compared with rest, MBV and forearm blood flow at 5 s of exercise were increased in the active arm but were reduced transiently in the inactive limb (P < 0.05). CONCLUSIONS: Conduit artery responses to exercise were dependent upon the work rate and arm position. The delayed dilation in the heavier exercise, independent of arm position, suggests that stimuli related to the metabolic activity of the distal active skeletal muscle may influence the dimensions of the conduit artery.

Adult↗
PubMed1997

Prophylactic balloon angioplasty fails to prolong the patency of expanded polytetrafluoroethylene arteriovenous grafts: results of a prospective randomized study.

PURPOSE: Maintenance of hemodialysis access grafts represents an enormous social and clinical problem. Current grafts and graft salvage techniques are inadequate. Consequently, there has been increasing interest in the use of minimally invasive catheter techniques to prophylactically treat stenoses in functioning arteriovenous grafts. Prophylactic balloon angioplasty has been widely suggested as prolonging assisted primary patency. We have performed a prospective randomized trial to compare patients who underwent percutaneous transluminal angioplasty (PTA) for graft stenoses > 50% with a control group that received no intervention. Our hypothesis was that to be efficacious a minimal benefit of 20% prolongation in patency would be necessary. METHODS: Color flow duplex scanning was used to detect > 50% stenoses in functioning expanded polytetrafluoroethylene grafts. Patients were then subjected to confirmatory angiographic evaluation. Those who had angiographic stenoses > 50% were randomized to balloon angioplasty or observation. Patients were followed-up with duplex scanning every 2 months. Statistical analysis was performed using the Kaplan-Meier technique. Although demographically the patient groups were well matched, there were more prior interventions and concurrent central stenoses in the treatment group. Outcomes were graft thrombosis, graft dysfunction that precluded dialysis, and six or more PTA procedures within 18 months. RESULTS: In the treatment and observation groups, the 6-month patency rates were 69% +/- 7% and 70% +/- 7%, respectively. The 12-month patency rates for the treatment and observation groups were 51% +/- 6% and 47% +/- 4%, respectively. There was no significant difference between these two groups (p = 0.97), with an 80% confidence limit for detection of a difference greater than 20%. CONCLUSIONS: This study demonstrates that a generic approach of PTA to treat all polytetrafluoroethylene grafts with stenoses > 50% does not prolong patency and cannot be supported.

Adult↗
PubMed1997

The thrombosed arteriovenous graft: an endovascular model for vascular surgeons.

Arteriovenous dialysis grafts are the most commonly implanted prosthetic grafts. Thrombectomy with selective graft revision is traditional therapy for occlusions, but patency is minimally prolonged. Stenoses are determined by tactile feedback from an embolectomy catheter and lack of prograde and retrograde bleeding. An objective method for studying the graft and inflow and outflow tracts that permits appropriate endoluminal or surgical correction is described. This approach is appealing because: (i) the current approach is inadequate; (ii) it offers an objective, quantitative method to determine frequency and severity of critical stenoses within the failed access graft; (iii) remote and perigraft stenoses can be treated at the same setting; and (iv) it promotes the development of endovascular skills by surgeons in a high-volume, low-risk setting.

Aged↗
PubMed1997

Central venous stenosis in the hemodialysis patient: incidence and efficacy of endovascular treatment.

Central venous stenosis occurs as a complication of central venous catheterization and significantly complicates delivery of dialysis through arteriovenous grafts in the ipsilateral upper limb. This report includes two separate studies. Functioning expanded polytetrafluorethylene grafts have been prospectively evaluated using duplex scanning and angiography performed in all patients with stenoses > 50%. From this, it has been prospectively established that the incidence of unsuspected central venous stenoses in patients with functioning grafts is 29%. In the second part of the report, the authors' experience in the treatment of 25 central venous stenoses with percutaneous angioplasty and stent placement has been retrospectively reviewed. Initial technical success rate was 88%. Primary patency was 84% at 1 month, 42% at 6 months, and 17% at 1 year. Mean primary patency was 5.7 months. Stents were placed in five patients. Prevention of central venous stenosis by avoiding subclavian catheterization is optimal. Balloon angioplasty provides short-term patency, but it is the only option in most cases. The role for endovascular stent placement remains to be defined but early results are not optimistic.

Angioplasty, Balloon↗
PubMed1997

A descriptive study of recurrent low back pain claims.

This is the first large-scale study of US workers that describes the demographic and cost differences between recurrent and nonrecurrent low back pain (LBP) disability claimants, using data from a large workers' compensation insurer. Persons with at least one LBP claim in 1990 and one or more additional claims in 1990 to 1996 were defined as recurrent. Persons with at least one LBP claim in 1990 but no subsequent claims were defined as nonrecurrent. Fourteen percent of claimants were recurrent. The percentage of recurrent claimants who were male (77.2%) was higher than the percentage that were female (22.8%). This difference was more pronounced in the younger age groups. The median total cost for recurrent LBP claims in 1990 was 4% greater than for nonrecurrent 1990 LBP claims, whereas the mean cost was 48% less. Most studies of LBP recurrence among US workers have followed single-corporation employees. Our rate of recurrence was lower than these previously reported rates. However, analysis of independent workers' compensation insurance company data may provide a more accurate assessment of LBP claim recurrence among US workers.

Adult↗
PubMed1997

Effect of acute plasma volume expansion on substrate turnover during prolonged low-intensity exercise.

We investigated the effect of acute, graded increases in plasma volume (PV) by use of dextran on substrate turnover and oxidation during exercise. Eight untrained males [peak aerobic power (VO2peak) = 45.2 +/- 2.2 (SE) ml.kg-1.min-1] performed 2 h of cycle ergometry at 46 +/- 4% of VO2peak on three occasions in a randomized order: 0% PV expansion (CON) and after 14% (LOW) and 21% (HIGH) PV expansion. Glucose and glycerol turnover were measured using primed continuous infusions of [6,6-2H2]glucose and [2H5]glycerol, respectively. Glycerol rate of appearance (Ra) was taken as a relative index of whole body lipolysis. Increases in PV had no effect on glucose Ra or disappearance (Rd) either at rest or during exercise. At the onset of exercise, both glucose Ra and Rd increased approximately 100% (P < 0.01). Glucose Ra and Rd continued to increase with exercise duration (P < 0.05) so that, at 120 min of exercise, they were > 330% higher than at rest (P < 0.01). Glycerol Ra also increased with exercise duration (P < 0.05). Total lipolysis during exercise, calculated as the area under the glycerol Ra vs. time curve, was reduced during LOW vs. CON (P < 0.01). Further expansion of PV (HIGH) had no additional effect on whole body lipolysis. No effect of hypervolemia was observed on whole body fat or carbohydrate oxidation. These results indicate that acute PV expansion can alter whole body lipolysis, possibly via a reduction in catecholamine secretion.

Adult↗
PubMed1997

Oscillations in activities of enzymes in pancreatic islet subcellular fractions induced by physiological concentrations of effectors.

Glucose, the most potent insulin secretagogue, stimulates insulin secretion by aerobic glycolysis, but other secretagogues stimulate insulin release exclusively by mitochondrial metabolism. It is well known that in the intact pancreatic beta-cell, either kind of secretagogue can induce oscillations in metabolism (e.g., glycolysis, ATP/ADP, NAD(P)/NAD(P)H ratios) that occur with a periodicity similar to oscillations in membrane electrical potential and insulin secretion. In this study, pancreatic islet cytosol or mitochondrial fractions were incubated in the presence of physiological concentrations of substrates. Repeated additions of physiological effectors caused oscillations in the activities of the three enzymes studied. Succinate dehydrogenase activity in islet mitochondrial extracts was made to oscillate by adding oxaloacetate (5 micromol/l) to inhibit the enzyme. The enzyme was reactivated by adding acetyl-CoA (3 micromol/l), which combines with oxaloacetate in the citrate synthase reaction and lowers the concentration of oxaloacetate, thus beginning another oscillation. Pyruvate kinase activity was made to oscillate by adding fructose bisphosphate (10 micromol/l). Fructose bisphosphate was degraded to triose phosphates fairly rapidly, and, as it was degraded, there was a parallel decrease in pyruvate kinase activity. The enzyme was reactivated and made to oscillate with subsequent additions of fructose bisphosphate. The mitochondrial glycerol phosphate dehydrogenase was made to oscillate by adding EGTA to chelate calcium, which activates the enzyme. When the concentration of free calcium was raised to >0.1 micromol/l by adding more calcium, the activity of the enzyme increased. Repeated additions of chelator and calcium caused the enzyme activity to oscillate. The results with these three enzymes and physiological concentrations of naturally occurring effectors raise the possibility that the activities of not only these enzymes but of numerous enzymes oscillate in vivo in response to levels of allosteric effectors and substrates. If this is the case, pacemaker activity may result from complex effects distributed across multiple regulatory sites in both the cytosol and mitochondria, rather than from a single enzyme acting as a primary pacemaker.

Acetyl Coenzyme A↗
PubMed1997

Infrainguinal bypass in end-stage renal disease: when is it justified?

Management of the patient with end stage renal disease and peripheral vascular disease represents a major challenge to the vascular surgeon. In this review, we developed guidelines for intervention based on our own institutional experience as well as literature review. There have been more than 290 patients reported to have 369 ischemic legs with threatened limb loss. There was an overall graft patency rate of 71% (range, 64% to 77%) and 60% (range, 48% to 90%) for 1 and 2 years, respectively. The mean limb salvage rate was 72% (range, 52% to 94%) at 2 years in these groups of patients. In the presence of rest pain and/or tissue loss, with favorable inflow and outflow (at least one vessel with direct flow into the foot), we strongly advised surgical bypass. In those patients who presented with rest pain and/or tissue loss, infragenicular surgical reconstruction led to a higher quality of life in comparison to patients with primary amputations. An indication for a primary amputation would be gangrene extending proximal to the mid foot. We have therefore outlined our findings and thoughts in the following article.

Arterial Occlusive Diseases↗
PubMed1997

Alveolar oxygen uptake and blood flow dynamics in knee extension ergometry.

The relationship was studied between the increase in oxygen uptake (VO2) measured breath-by-breath at the mouth, and the increase in femoral artery blood flow measured continuously with pulsed and echo Doppler methods. Five men exercised at 50 W on a knee extension ergometer in both the supine and the upright posture. The kinetics of the responses were determined by curve fitting to obtain the mean response time (MRT = 63% of the time required to achieve steady state). In the upright position, the increase in blood flow (MRT = 12.4 +/- 9.4 s, mean +/- SD) was faster than the increase in VO2 (29.6 +/- 9.3 s). Likewise in the supine position, blood flow increased more rapidly (25.1 +/- 9.7 s vs. 36.7 +/- 9.6 s). It should be noted that the increase in blood flow appeared to be faster than VO2, yet when blood flow adapted more slowly in the supine posture, it had an impact on the adaptation of VO2. This suggests that blood flow might have important effects on metabolism at the onset of submaximal exercise.

Blood Flow Velocity↗