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Biomedical subjects

R J Barnard

Publications and source records attributed to R J Barnard.

At least 91 records · Page 5Linked to original sources

Compliance studies, pressure flow measurements and renal function assessment in patients with upper urinary tract dilatation.

The compliance index was determined in 38 hydronephrotic kidneys undergoing diagnostic pressure flow studies. A good correlation was found between this index and the result of the pressure flow study but no consistent relationship was observed between the index and relative renal function as assessed by renographic means. The ability of the compliance index to predict functional deterioration in patients with hydronephrosis must be questioned.

Adult↗

Effect of diet on insulin binding and glucose transport in rat sarcolemmal vesicles.

The purpose of this study was to compare the effects of a high-fat, high-sucrose diet (HFS) and a low-fat, high-complex carbohydrate diet (LFC) on glucose tolerance, insulin binding, and glucose transport in rat skeletal muscle. During the intravenous glucose tolerance test, peak glucose values at 5 min were significantly higher in the HFS group; 0-, 20-, and 60-min values were similar. Insulin values were significantly higher in the HFS group at all time points (except 60 min), indicating whole-body insulin resistance. Skeletal muscle was responsible, in part, for this insulin resistance, because specific D-glucose transport in isolated sarcolemmal (SL) vesicles under basal conditions was similar between LFC and HFS rats (35 +/- 5 vs. 32 +/- 4 pmol/mg protein), despite the higher plasma insulin levels. Scatchard analyses of insulin binding curves to sarcolemmal vesicles revealed that the Ka of the high-affinity binding sites was significantly reduced by the HFS diet (0.63 +/- 0.09 vs. 0.35 +/- 0.05 X 10(9) M-1); no other binding changes were noted. Specific D-glucose transport in SL vesicles after maximum insulin stimulation (1 U/kg) was significantly depressed in the HFS group (87 +/- 7 vs. 58 +/- 7 pmol/mg protein), indicating that HFS feeding also caused a postbinding defect. These results indicate that the insulin resistance in skeletal muscle associated with a HFS diet is due to both a decrease in the Ka of the high-affinity insulin receptors and a postbinding defect.

Animals↗

Evaluation of reactions to food additives: the aspartame experience.

Despite the widespread use of chemical food additives, few criteria exist to evaluate consumer reports of adverse reactions. We analyzed 231 consumer complaints associated with the food additive aspartame. We developed a methodologic approach to evaluate all complaints by adapting general criteria used to investigate adverse reactions to medications. Complaints were ranked according to the effects of cessation and rechallenge. Using this method, we found no clear symptom complex that suggests a widespread public health hazard associated with aspartame use; however, we identified some case reports in which the symptoms may be attributable to aspartame in commonly-consumed amounts. The systematic application of pre-defined review criteria, such as those described here, to monitor consumer complaints related to food additives will help identify products that warrant more focused clinical studies.

Adult↗

Effect of training on insulin binding to rat skeletal muscle sarcolemmal vesicles.

We examined the hypothesis that the exercise training-induced increase in skeletal muscle insulin sensitivity is mediated by adaptations in insulin binding to sarcolemmal (SL) insulin receptors. Insulin binding studies were performed on rat skeletal muscle SL isolated from control and trained rats. No significant differences were noted between groups in body weight or fat. An intravenous glucose tolerance test showed an increase in whole-body insulin sensitivity with training, and specific D-glucose transport studies on isolated SL vesicles indicated that this was due in part to adaptations in skeletal muscle. Enzyme marker analyses revealed no differences in yield, purity, or contamination of SL membranes between the two groups. Scatchard analyses indicated no significant differences in the number of insulin binding sites per milligram SL protein on the high-affinity (15.0 +/- 4.1 vs. 18.1 +/- 6.4 X 10(9)) or on the low-affinity portions (925 +/- 80 vs. 884 +/- 106 X 10(9)) of the curves. The association constants of the high-affinity (0.764 +/- 0.154 vs. 0.685 +/- 0.264 X 10(9) M-1) and of the low affinity sites (0.0096 +/- 0.0012 vs. 0.0102 +/- 0.0012 X 10(9) M-1) also were similar. These results do not support the hypothesis that the increased sensitivity to insulin after exercise training is due to changes in SL insulin receptor binding.

Animals↗

Biochemical studies: failure of tissue adenosine triphosphate levels to predict recovery of contractile function after controlled reperfusion.

This study tests the hypotheses that postischemic adenosine triphosphate levels are unreliable predictors of functional recovery, myocardial adenosine triphosphate concentration of less than 2 mumol/gm does not indicate irreversible damage, mitochondrial adenosine triphosphate generating capacity can be nearly normal despite low levels of tissue adenosine triphosphate and the failure to replenish adenosine triphosphate after ischemia is due to depletion of the adenosine nucleotide pool, which can be replenished partially by exogenous precursors (e.g., 5-amino-4-imidazolecarboxamide ribotide [AICAR]). Myocardial adenosine triphosphate was depleted to less than 2 mumol/gm by either global ischemia (37 degrees C aortic clamping) or regional ischemia (acute coronary occlusion). Reperfusion was either with normal blood or with substrate-enriched blood cardioplegic solution during total vented bypass. Tissue adenosine triphosphate content and mitochondrial adenosine triphosphate generating capacity were measured, and functional recovery was determined by right heart bypass function curves or regional segmental shortening (ultrasonic crystals). Hearts undergoing 15 minutes of global ischemia and normal blood reperfusion had impaired functional recovery (stroke work index = 58 +/- 5%; p less than 0.05 of control) despite adenosine triphosphate concentration greater than 2 mumol/gm. Transmural mitochondrial State 3 respiration averaged 83% of control values despite adenosine triphosphate levels of 1 mumol/gm in hearts undergoing 45 minutes of 37 degrees C global ischemia and 2 additional hours of aortic clamping with multidose glutamate-enriched blood cardioplegia. AICAR increased adenosine triphosphate to 2 mumol/gm (p less than 0.05), but functional recovery was nearly complete (stroke work index = 94 +/- 2% of control) and was comparable with and without AICAR. Hearts undergoing 4 hours of regional ischemia recovered 31 +/- 5% systolic shortening after controlled reperfusion despite tissue adenosine triphosphate less than 0.5 mmol/gm (15% of control), and they retained 63% adenosine triphosphate generating capacity. Postischemic adenosine triphosphate levels correlate poorly with functional recovery, and adenosine triphosphate levels less than 2 mumol/gm do not indicate irreversible ischemic injury. Low postischemic levels may be repleted partially by adenine nucleotide precursor supplementation (AICAR).(ABSTRACT TRUNCATED AT 400 WORDS)

Adenosine Triphosphate↗

Histochemical studies: inability of triphenyltetrazolium chloride nonstaining to define tissue necrosis.

Triphenyltetrazolium chloride has been used to detect irreversibly damaged tissue after regional ischemia and reperfusion. We used this staining technique in our studies of myocardial ischemia and reperfusion and found that a transmural triphenyltetrazolium chloride nonstaining pattern is not an accurate predictor of myocardial necrosis: functional recovery occurs despite nonstaining. Mongrel dogs (n = 91) were anesthetized and made ischemic by ligation of the left anterior descending coronary artery. Regional myocardial function was assessed by means of ultrasonic crystals. Following 2, 4, or 6 hours of ischemia, the ligature was removed, and each heart was reperfused either in the working state or during total bypass with either normal blood or substrate-enriched blood cardioplegic solution of differing composition. The hearts were then removed and incubated in triphenyltetrazolium chloride at 37 degrees C for 20 to 40 minutes. The pattern of nonstaining in the area at risk varied from patchy subendocardial, to confluent subendocardial, to transmural and did not correlate with the recovery of regional contraction following ischemia. Mitochondrial ultrastructure was altered minimally in nonstained muscle, which regained contractile function after 6 hours of ischemia. Fifty-two of sixty-five hearts (80%) showing a transmural nonstaining pattern in the area of ultrasonic crystal placement recovered the capacity to shorten systolically immediately after controlled reperfusion during total vented bypass. These results show that the triphenyltetrazolium chloride staining method does not predict myocardial necrosis and that appropriate reperfusion following 2 to 6 hours of ischemia will result in recovery of myocardial shortening despite transmural nonstaining.

Animals↗

Electron microscopic studies: importance of embedding techniques in quantitative evaluation of cardiac mitochondrial structure during regional ischemia and reperfusion.

This study applies the low protein-denaturation embedding technique for mitochondrial preparation to analyze control cardiac tissue, heart muscle subjected to 6 hours of regional ischemia without reperfusion, and myocardial tissue subjected to 4 to 6 hours of ischemia followed by reperfusion either with normal blood, with the heart in the beating, working state, or with substrate-enriched blood cardioplegia during total vented bypass. Parallel specimens of cardiac tissue were analyzed for ultrastructure by the conventional osmium tetroxide fixation method. Results following conventional tissue preparation with osmium tetroxide showed extensive ultrastructural damage in all hearts subjected to ischemia, with no correlation between ultrastructural findings and methods of reperfusion or functional recovery. In contrast, results following tissue preparation by the low protein-denaturation method showed reperfusion with normal blood in working hearts to cause severe mitochondrial damage, cardiac mitochondria that were intact structurally after 6 hours of ischemia and after controlled reperfusion, a logical sequence of mitochondrial structural changes that may lead to irreversibility, and a new method of quantification of such changes.

Animals↗

Triathlete characterization and response to prolonged strenuous competition.

The purpose of this study was to characterize triathletes and to assess their responses to prolonged, strenuous competition. Nine triathletes (6 males, 3 females) participated. Mean V0(2)max and percentage of body fat were 72.0 ml X kg-1 X min-1 and 7.1%, respectively, in the four males who finished in the top 15. This compared to values of 58.4 ml X kg-1 X min-1/10.2% and 58.7 ml X kg-1 X min-1/12.6% in the other males and females, respectively. In the 5 wk preceding competition (Hawaii "Ironman Triathlon World Championship") the average daily training of the four top 15 male competitors consisted of swimming 2720 m, running 13.6 km, and biking 84.0 km. This was approximately 1.5 times greater than that of the other athletes. The average training diet was 59% carbohydrate, 21% fat, and 20% protein. Immediately following competition, SGOT, SGPT, and serum LDH were increased 700, 262, and 222% (P less than 0.004), respectively, and still remained marginally elevated 5-6 d later (P less than 0.02). Immediately following competition, serum triglycerides remained unchanged, while serum glucose, glycerol, and nonesterified fatty acids increased 52, 248, and 191% (P less than 0.005), respectively. By 5-6 d post-competition glucose had returned to normal, while triglycerides were elevated 94% (P less than 0.005) and nonsterified fatty acids were decreased 58% (P less than 0.01).

Alanine Transaminase↗

Effects of a high-complex-carbohydrate, low-fat, low-cholesterol diet on levels of serum lipids and estradiol.

Recent studies have implicated elevated levels of serum estradiol in males as the major predisposing factor for myocardial infarction, with serum cholesterol playing a secondary role. The purpose of the present study was to investigate the effects of a high-complex-carbohydrate, low-fat, low-cholesterol diet and daily exercise on levels of serum estradiol, testosterone, and lipids in males. Twenty-one males participating in the Pritikin Longevity Center 26-day residential program volunteered for the study. During the program, serum estradiol levels were significantly reduced from 47.2 +/- 4.6 to 23.8 +/- 2.5 pg/ml (mean +/- SE) whereas serum testosterone levels were unchanged (5.1 +/- 0.3 versus 5.1 +/- 0.2 ng/ml). Total serum cholesterol levels were reduced from 229 +/- 9 to 181 +/- 7 mg/dl whereas triglyceride levels were reduced from 301 +/- 66 to 151 +/- 13 mg/dl. High-density lipoprotein-cholesterol levels fell from 41 +/- 3 to 35 +/- 1 mg/dl whereas the ratio of total cholesterol to high-density lipoprotein-cholesterol was unchanged (5.5 +/- 0.4 versus 5.1 +/- 0.3).

Blood Glucose↗

Morphological and morphometric studies of the human obstructed, trabeculated urinary bladder.

As part of an ongoing study on trabeculation of the human urinary bladder, morphological and morphometric techniques have been employed on biopsy samples of detrusor muscle removed from control and urodynamically obstructed patients. In control material the mean profile area, profile diameter and nucleated profile percentage of bladder smooth muscle cells were determined. The values of the same parameters were obtained for smooth muscle cells in samples from urodynamically obstructed and endoscopically trabeculated patients. Comparison of the results obtained from the two groups showed that smooth muscle cells undergo compensatory hypertrophy in response to outflow obstruction. Furthermore, connective tissue infiltration of detrusor muscle bundles is a characteristic of those bladders which possess cells showing the largest increase in cell size.

Adult↗

A comparison of diuresis renography, the Whitaker test and renal pelvic morphology in idiopathic hydronephrosis.

Diuresis renography and the Whitaker test are established methods of diagnosing obstruction in dilated renal pelves. These techniques have been compared in 36 patients with radiologically demonstrated idiopathic hydronephrosis and evaluated, where possible, against renal pelvic morphological features. The agreement between the results of the tests was as follows: diuresis renography/Whitaker test 67%; diuresis renography/renal pelvic morphology 74%; Whitaker test/renal pelvic morphology 58%. Both diuresis renography and the Whitaker test are indicated in some cases of idiopathic hydronephrosis.

Diuresis↗

Pressure changes in the dilated upper urinary tract on perfusion at varying flow rates.

The conventional Whitaker test assesses the pressure response to a constant perfusion rate of 10 ml/min. Twenty-eight kidneys were perfused at increasing flow rates up to 20 ml/min. Nine became obstructed at rates of 12 to 20 ml/min. The feasibility of such a high urine output has been tested and confirmed. The standard Whitaker test may therefore miss some cases with potentially obstructive hydronephrosis, the effects of which may be deleterious to renal function.

Adolescent↗

Insulin binding and glucose transport in rat skeletal muscle sarcolemmal vesicles.

A new method is described for isolation of sarcolemma (SL) from skeletal muscle of rats that produces vesicles of high purity and yield. There was a mean 59-fold purification (n = 22) of the SL marker enzyme K+-p-nitrophenylphosphatase. Specific activities of marker enzymes for sarcoplasmic reticulum and mitochondria were low, indicating minimal contamination. Despite the high purity and low contamination, a relatively high protein yield was achieved (0.43 +/- 0.03 mg/g wet wt, n = 25). Electron microscopy showed that the membranes were primarily vesicles. Specific 125I-insulin binding association constants derived from the high- and low-affinity portion of the Scatchard plots were 0.764 +/- 0.154 and 0.0096 +/- 0.0012 X 10(9) M-1, whereas the apparent number of receptors were 15.0 +/- 4.1 and 925 +/- 80 X 10(9) per mg of SL protein. Equilibrium exchange glucose transport studies at 37 degrees C indicated that the SL vesicles exhibited specific D-glucose transport which was responsive to in vivo insulin stimulation. We conclude that this isolation procedure, especially in light of the high purity and yield, provides a good and practical experimental model for studying insulin binding and glucose transport in skeletal muscle.

Animals↗

Renal pelvic pressures in human chronic obstructive uropathy.

Resting renal pelvic pressure and premicturition bladder pressure have been measured by direct percutaneous puncture in 12 male patients with established chronic obstructive uropathy related to high pressure chronic retention. In 10 technically satisfactory cases the subtracted renal pelvic pressure was less than the intrinsic bladder pressure, showing that upper tract dilatation and diminished renal function in these patients were not due to direct extension of high resting bladder pressure into the upper tract. The mean resting upper tract pressure in chronic human obstructive uropathy was 10.7 cm of water.

Chronic Disease↗

Practical management of patients with dilated upper tracts and chronic retention of urine.

Patients with chronic retention of urine associated with dilated upper tracts have been investigated by means of combined lower tract urodynamics and upper tract renography. It has been shown that minor alterations in bladder volume lead to marked changes in isotope washout from the upper tracts. It is concluded that the practice of slow decompression of the bladder in these patients is clinically impractical, and attention should be directed to the management of the post-obstructive diuretic state. Further observations have suggested that upper tract drainage in such patients may be dependent upon postural factors, and the practical implication of this finding is discussed.

Adult↗

Cardiac hypertrophy and function in master endurance runners and sprinters.

Cardiac enlargement with increased left ventricular mass is a recognized adaptive response to intensive physical conditioning. There have been few reports regarding cardiac hypertrophy and function in the middle-aged or older athlete. Accordingly, we studied 9 male Masters Track endurance distance runners (E) (mean age 54 yr) and 13 male Masters Track sprinters (S) (mean age 47 yr) by M-mode echocardiography, systolic time intervals, and maximal treadmill stress testing with direct measurement of maximal O2 consumption (VO2max). Left ventricular mass (LVM) index for E (154.0 +/- 27.4 g/m2; mean +/- SD) was greater than for S (127.1 +/- 15.9 g/m2) (P less than 0.05). LVM index was greater for both groups compared with age-range matched controls (N = 111.7 +/- 23.8 g/m2) (P less than 0.02). VO2max was greater in E (54 +/- 12 ml X kg-1 X min-1) than S (47 +/- 7 ml X kg-1 X min-1) (P less than 0.05) despite the younger age of S (P less than 0.05); both E and S had greater VO2max than predicted for nonathletic males of equivalent age. There was no significant linear relationship for LVM index and VO2max in the athletes. Left ventricular function at rest was normal. Thus, in well-trained older (greater than or equal to 40 yr) male distance runners and sprinters VO2max and LVM index are greater in E than S, and each greater than in controls, resting left ventricular function is normal, as judged by fractional shortening and systolic time intervals, and the degree of hypertrophy (LVM index) does not directly correlate with aerobic capacity (VO2max).

Adaptation, Physiological↗