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Biomedical subjects

J T Baker

Publications and source records attributed to J T Baker.

At least 37 records · Page 2Linked to original sources

Anatomic and prognostic implications of an early positive treadmill exercise test.

Eighty men (group A) with clinical coronary artery disease underwent coronary angiography regardless of symptoms and previous therapy because they had a positive treadmill exercise test in stage I or II of the Bruce protocol. Thirty-four other men (group B) who also had an early positive treadmill test underwent coronary angiography because they had disabling angina pectoris despite medical therapy. We found left main coronary artery stenosis of 50% or greater of the vessel diameter in 28% of group A and 35% of group B (p greater than 0.3). In contrast, only 10% of 93 other catheterized patients who had treadmill tests that were not early positive had left main coronary disease (p less than 0.001). Fifty-four patients from group A who did not have left main stenosis of 50% or greater were treated medically. In this subgroup, 85% had 2 or 3 major coronary vessels with 75% or greater stenosis. These patients had a 36 month survival rate of 89.2%. We conclude that an early positive treadmill test identifies patients who have an increased likelihood of having left main coronary stenosis, even if they are minimally symptomatic. To identify left main coronary stenosis, catheterization may be justified in patients whose angina pectoris has been mild or not intensively treated when they have an early positive treadmill response. After left main coronary stenosis has been excluded, these patients may be treated medically with a low mortality.

Adult↗

Pirmenol, a new antiarrhythmic agent: initial study of efficacy, safety and pharmacokinetics.

Pirmenol (CI-845), a new antiarrhythmic drug, was studied for the first time in humans to establish a minimum effective i.v. dose in 10 patients with chronic, stable premature ventricular complexes (PVCs) and to evaluate toxicity and pharmacokinetics. Infusions of 70-150 mg were associated with a 90% or greater reduction in PVCs nine of the 12 times they were administered to six patients. Peak plasma concentrations were 1.0-3.8 micrograms/ml at the end of these infusions. At the same time, small but significant increases in diastolic blood pressure (4 mm Hg) and QTc interval (0.01 second) were seen, but both values were within the normal range. Pirmenol was associated with no change in heart rate, systolic blood pressure, PR interval or QRS duration, renal, hepatic or hematologic function, or symptoms. Blood, plasma and free drug concentrations declined biexponentially after cessation of a 150-mg infusion (n = 4), with a terminal half-life of 7-9.4 hours. The therapeutic response, lack of toxicity, and relatively long half-life indicate that pirmenol is a promising antiarrhythmic agent.

Anti-Arrhythmia Agents↗

Myocardial infarct extension: incidence and relationship to survival.

Myocardial infarct extension, defined as reelevation or reappearance of creatine phosphokinase-MB (CK-MB) 48 hours after the onset of symptoms, was evaluated prospectively in 56 consecutive patients with acute myocardial infarction. Myocardial infarct extension occurred in eight patients (14%). The sensitivity, specificity and predictive accuracy in the diagnosis of myocardial infarct extension were 63%, 85% and 42%, respectively, for recurrent chest pain requiring morphine; 50%, 65% and 19% for recurrent ST-segment elevation on routine 12-lead ECGs; and 88%, 63% and 28% for reelevation of total CK. Three of the eight episodes of extension were clinically silent. Four of eight patients (50%) with extension died, compared with one of 46 patients (2%) without extension (p = 0.0009). CK-MB persisted for 72 hours or longer in 16 patients and identified seven of eight patients who subsequently had infarct extension. We conclude that myocardial infarct extension is an infrequent complication of acute myocardial infarction and is associated with a very high mortality rate. Persistence of CK-MB for 72 hours or more identifies a subgroup of patients at high risk for subsequent infarct extension and death.

Creatine Kinase↗

Development of the intrarenal vascular system of the puppy kidney.

This study investigates the development of the vascular system of the puppy kidney (1-21 days after birth) after preparing casts of the renal vessels. At two days, the intrarenal vascular system distal to the afferent arteriole is strikingly different than that of the adult. The glomeruli of the outer cortex consist of a single dilated vessel while those of the mid and inner cortex posses an increasingly larger number of capillary loops. The efferent arterioles vary greatly in appearance from outer to inner cortex. Those in the nephrogenic zone are characteristically short and narrow and join a larger venous vessel termined a sinusoidal capillary. An efferent system somewhat similar to that of the adult is seen in the mid and inner cortex. One of the most obvious differences noted between the puppy and adult kidney is the relative lack of peritubular capillary networks throughout the cortex of the puppy kidney. The puppy possesses large, irregular vessels termed sinusoidal capillaries. The most rudimentary sinusoids are found in the outer cortex with more mature vessels in the inner cortex. The vascular arrangement of the efferent arteriole and sinusoidal capillary appears as a post-glomerular shunt. Functionally, the shunt would direct blood flow away from the proximal tubule and thus could result in a low extraction ratio and Tm for secreted solutes.

Aging↗

Dependence of p-aminohippurate transport on calcium in canine renal cortical slices.

1. Experiments were conducted on renal cortical slices from sixty-one adult mongrel dogs in order to evaluate the relationship between p-aminohippurate (PAH) transport and calcium. Tissues were found to be viable for at least 180 min.2. PAH uptake and the slice/medium (S/M) concentration ratio increased in normal tissues from 3 to 90 min whether data were expressed on a tissue weight or protein content basis. PAH uptake increased with time in calcium-depleted tissues, but all values were lower than normal. At 90 min, PAH S/M in calcium-depleted tissues (4.20 +/- 0.18) was reduced 40% compared to normal tissues (6.90 +/- 0.23).3. Over the time period of 3-90 min incubation, protein concentration ranged from 89.4 to 99.4 mg/g cortex in calcium-depleted tissues. During the same time period in normal tissues, protein concentration ranged from 105 to 117.6 mg/g cortex. No change was observed in medium protein concentration of calcium-depleted tissues.4. Lineweaver-Burke analysis showed similar values for K(m) in normal and calcium-depleted tissues (0.45-0.50 mumole ml.(-1)) although V(max) fell from control values of 0.082 to 0.052 mumole g(-1) min(-1) during calcium depletion.5. After 90 min incubation, addition of EGTA (7, 14 or 21 x 10(-3)M) to media containing calcium was associated with decreased S/M and uptake rates compared to control values from the same animals. The decreases observed were similar to those seen in tissues incubated in calcium-free media.6. Increased cell volume in the presence of calcium was not associated with decreased PAH uptake. Removal of calcium in association with constant cell volume was associated with reduced PAH uptake. Replacement of calcium, but not magnesium, is associated with a return of uptake to normal rates.7. It is concluded that (a) calcium removal causes increased water uptake into cells, (b) calcium removal causes a reduced V(max), (c) calcium is required for maintenance of intracellular PAH, (d) the effect of calcium on PAH is specific and reversible, and (e) the effect of calcium is not mediated by volume changes.

Aminohippuric Acids↗

Extraction fraction at any urine flow and extraction percentage.

Extraction fraction of renal solutes is ordinarily calculated as a ratio of arterial and venous concentration differences. Calculations provided in the present manuscript illustrate the need to correct for changes in renal venous concentration when solute extraction is low and urine flow simultaneously high.

Humans↗

Zonulae occludentes of the rat nephron under conditions of experimental expansion of blood and/or fluid volume.

The zonula occludens (Z.O.) has been implicated as a major pathway for passive fluid movement from lateral intercellular spaces to lumen in response to an expansion of blood or fluid volume. The present study examines to Z.O. of adult rat nephrons in control and Ringer-Locke or while blood infused animals to determine whether varying the conditions of passive fluid movement would influence the structure of the Z.O. Rats were infused over 20 minutes with Ringer-Locke (7% body weight) or while blood (2.3% body weight). In the controls, 92%-94% of all Z.O. observed in proximal tubules and 100% of Z.O. from distal tubules and collecting ducts had fused outer leaflets. The approximate linear extent of the Z.O. was 140 A for proximal tubules, 2,500 A for distal tubules and 3,000 A for collecting ducts. There was no significant difference in any of these values following the infusion with either Ringer-Locke or whole blood. We conclude that expansion of blood or fluid volume causes no detectable alteration in the fine structure of Z.O. under the conditions used in the present study.

Animals↗

Maturation of the renal response to hypertonic sodium chloride loading in rats: micropuncture and clearance studies.

1. The ability of maturing rats to excrete a sodium load was studied by micropuncture and clearance procedures. 2. During control conditions, no change of glomerular filtration rate or sodium excretion was observed for the time period of the entire procedure (P greater than 0-20). During the infusion of hypertonic (4%) sodium chloride, fractional sodium excretion was 0-08 +/- 0-01 in rats 21-30 days old and 0-14 +/- 0-01 (P less than 0-01) in adults. However, the depression of proximal tubular water re-absorption was equal in both groups (P greater than 0-20). 3. Proximal glomerulotubular balance for water re-absorption was similar in all groups (P less than 0-20). Since end proximal tubular water excretion and depression of fractional water excretion were the same in all animals, differences of urinary sodium excretion during development are probably due to differences of function of segments beyond the proximal tubule during development. 4. Fractional potassium excretion was reduced in young rats (0-17 +/- 0-04) during hypertonic sodium chloride infusion, compared to adults (0-24 +/- 0-01, P less than 0-05). 5. Passage time of fast green through cortical segments in seconds is prolonged in young rats during control conditions. Similar decreases of passage time were seen in all groups during hypertonic sodium chloride infusion. No segmental differences of passage time were seen during developmental. 6. No difference in the relationship between fractional sodium and water excretion was seen during development of the renal response to hypertonic sodium chloride infusion. Thus, altered sensitivity to sodium chloride osmotic diuresis does not exist during maturation in rats.

Age Factors↗

Measurement of a single tendon reflex in conjunction with a myogram: the second manned Skylab mission.

A generalized hyperreflexia was observed in Skylab 2 crewmembers during the immediate postflight clinical evaluations. Unfortunately, no provisions had been made to quantitate the observed phenomenon. The cause of the hyperreflexia was not readily apparent at the time of the observation. Reflex changes have been noted in several of the Russian cosmonauts after extended spaceflight. Prior to the launch of Skylab 3, it was decided to measure and record a single tendon reflex and, if possible, the associated muscle potential. Duration of the Achilles reflex immediately postflight showed a significant (p greater than 0.01) shortening for all three crewmen. The reflex duration exhibited further significant shortening from preflight values on the fourth day after recovery. At the 16th day measurement, there was a signficant lengthening of the reflex for crewmenber 2 and 3 while crewmember 1 showed some lengthening which was not significant. By 29 d postrecovery, the reflex time of crewmember 1 had returned to his preflight value while the other two crewmen continued to show a significant lengthening of the reflex, although both were showing trends toward their preflight values. The muscle potential intervals were shortened immediately postflight and remained shortened during the 29 d of postflight evaluation. Currently, work is in progress to correlate these findings with other observed anatomical, physical, and biochemical changes. Final conclusions and an in-depth statistical analysis will be presented at a later date.

Adult↗

Relationship between glucose and sodium excretion in the new-born dog.

1. The relationship between renal glucose and sodium excretion was studied in thirty-three new-born dogs aged 1-14 days and in ten adult dogs.2. Glucose was infused into the animals at rates sufficient to produce an amount of filtered glucose at least 1.5 times the tubular transport of glucose (saturating glucose load). In both puppies and adults tubular glucose reabsorption at saturating glucose loads varied directly with the glomerular filtration rate (r = 0.54 and 0.73 respectively, P < 0.01 for both).3. In the puppy, as the fraction of filtered sodium excreted (C(Na)/C(In)) increased from 0.05 to 0.45, the ratio, renal tubular glucose transport divided by glomerular filtration rate at saturating glucose loads, (T(G)/GFR)(m), decreased from 3.7 to 1.7 mg/ml. (r = -0.75, P < 0.01). In the adult C(Na)/C(In) was below 0.08 in all experiments and (T(G)/GFR)(m) was within the 95% confidence limits predicted by regression analysis of the data from puppies. Although mean (T(G)/GFR)(m) was greater in the adult than in the puppy (P < 0.01), when puppies had C(Na)/C(In) similar to that for adults, they had (T(G)/GFR)(m) values equivalent to that for the adult.4. There was excellent correlation between glucose excretion and water excretion for both adult and new-born dogs (r = 0.93 and 0.87, respectively). However, for any glucose loss, water loss was greater in the puppy than in the adult (P < 0.01).5. During the control period total sodium excretion (per gram kidney) and C(Na)/C(In) were similar in the new-born and adult dog. However, during glucose loading, the puppies excreted more sodium and had a higher C(Na)/C(In) than did the adult, although glucose excretion was greater in the adult than in the puppy (P < 0.01 for all comparisons).6. Glomerular blood flow, as measured by radioactive microspheres, was redistributed towards inner cortical nephrons during glucose loading in the puppy. There was no such redistribution of glomerular blood flow in the adult.7. Sodium reabsorption beyond the proximal tubule was blocked with ethacrynic acid and chlorothiazide. In the puppy, the increase of C(Na)/C(In) following a glucose load was the same whether the glucose load followed control or distal blockade collections, suggesting that reductions of sodium reabsorption following a glucose load probably came from the proximal tubule. C(Na)/C(In) during glucose loading plus distal blockade was significantly (P < 0.01) higher in the puppy (0.598) than in the adult (0.280), indicating that glucose diuresis produced a greater inhibition of proximal tubular sodium reabsorption in the new-born than in the adult dog. These results support the hypothesis that the high sodium excretion rate during glucose diuresis in the new-born dogs appears to be due to the greater sensitivity of the neonatal proximal tubule to the osmotic effect of glucose. When presented with a glucose osmotic load the new-born dog diminishes net proximal sodium reabsorption more than does the adult and thus depresses tubular glucose reabsorption to a greater extent. The lower values of maximal glucose transport rates found in new-born animals may be related, therefore, to the higher fractional sodium excretion rates during glucose diuresis rather than to a diminished intrinsic glucose transport capacity in the new-born kidney.

Age Factors↗

Bowel habit in thyrotoxicosis and hypothyroidism.

A prospective study of bowel frequency in patients with thyroid disease showed increased frequency of bowel action in thyrotoxicosis and decreased frequency in myxoedema. The contrary findings of previous studies may be due to the use of inexact criteria in interrogation of the patients.

Constipation↗