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Biomedical subjects

M M Hunt

Publications and source records attributed to M M Hunt.

At least 19 recordsLinked to original sources
PubMed1997

Adult psychosocial outcome in early-treated phenylketonuria.

Concerns about the psychosocial risk of adults with early-treated phenylketonuria (ETPKU) are predicated on four sources of scientific data: (1) consistent documentation of increased behavioural risk in children with ETPKU; (2) recent evidence of neurocognitive impairment in adults with ETPKU; (3) reports of neuroimaging abnormalities in adults with ETPKU; and (4) preliminary evidence of increased rates of psychiatric disturbance in this population. We studied the psychosocial adjustment of 25 patients, aged 18 years and older, with ETPKU. On most psychosocial outcome measures, patients were indistinguishable from 15 sibling controls. However, on a self-report inventory of psychiatric symptoms, 20% of the patients demonstrated significant morbidity. Psychosocial outcome of these patients was unrelated to concurrent or historical biological dietary disease factors, unlike neurocognitive outcome. A strong relationship was demonstrated, however, between neurocognitive measures and psychosocial morbidity. These findings indicate that a significant minority of patients with ETPKU develop psychosocial difficulties with multiple clinical elevations on a psychiatric inventory. However, most adults with ETPKU cope with the challenges of young adulthood with the same degree of success as their unaffected siblings. Neuropsychological surveillance during childhood and adolescence is important in identifying patients at risk for both neurocognitive and psychosocial morbidity.

Adult↗
PubMed1994

Early-treated phenylketonuria: adult neuropsychologic outcome.

Twenty-five adults with phenylketonuria that was treated early were compared with 15 unaffected control siblings with respect to intellectual and neuropsychologic measures. Patients were found to have normal intelligence but were significantly lower than their control siblings on measures of intelligence, attention, and complex visuoconstructional ability. Stepwise multiple regression analyses found the patients' intellectual outcome to be best predicted by indexes reflecting early insult to the brain, whereas performance on a measure of novel problem solving was best predicted by concurrent serum phenylalanine level. Different pathophysiologic mechanisms may thus account for cognitive deficits in this population. These results provide further evidence of continuing benefits of dietary adherence into adulthood.

Adult↗
PubMed1992

Effect of dehydration on cardiovascular responses and electrolytes after hypertonic saline/dextran treatment for moderate hemorrhage.

STUDY OBJECTIVE: To determine if hypertonic saline/dextran (HSD) is effective in treating hemorrhage in the presence of dehydration. DESIGN: After surgical preparation, swine were euhydrated or dehydrated for 24 or 48 hours. Animals were bled 25 mL/kg over 60 minutes and treated with HSD. SETTING: Laboratory. PARTICIPANTS: Seventeen immature Yorkshire pigs. INTERVENTIONS: 4 mL/kg HSD (7.5% NaCl in 6% dextran-70) administered over one minute. MEASUREMENTS AND MAIN RESULTS: All euhydrated animals survived; 100% of the pigs survived 180 minutes after treatment. Two animals dehydrated for 24 hours and three animals dehydrated for 48 hours died within three hours of HSD treatment. In all groups, plasma potassium was reduced significantly and equally; cardiac output was increased; mean arterial pressure rose rapidly within first five minutes, but was sustained only in euhydrated animals; hematocrit, hemoglobin, and plasma total protein levels were reduced; and plasma glucose increased with persistent between-group differences. RESULTS: HSD immediately rectified the decreases in mean arterial pressure and cardiac output incurred during hemorrhage; over time, however, the improvement in pressure was not sustained in dehydrated pigs. Parallel increases in plasma osmolality and sodium concentrations were offset by the initial group differences resulting from dehydration. CONCLUSION: Dehydration does not compromise the efficacy of HSD as a resuscitation treatment for hemorrhagic shock.

Animals↗
PubMed1991

Neuroendocrine responses to hypertonic saline/dextran resuscitation following hemorrhage.

The neuroendocrine responses to resuscitation with 7.5% hypertonic saline/6% Dextran-70 (HSD) following hemorrhagic hypotension were evaluated in conscious swine. Following hemorrhage (37.5 ml/kg/60 min) animals received 4 ml/kg of HSD (n = 6) or 0.9% saline (n = 8). Administration of normal saline did not alter cardiovascular function nor attenuate an increase in hormones. HSD rapidly improved cardiovascular function and acutely decreased ACTH, plasma renin activity (PRA), cortisol, norepinephrine (NE), epinephrine (E), aldosterone, and lysine vasopressin levels (LVP). The initial decreased in ACTH, cortisol, and aldosterone levels was due primarily to hemodilution associated with the expansion of plasma volume. The reductions in NE, E, LVP, and PRA were greater than those attributed to hemodilution alone. Values for LVP, NE, and E remained at values below those at the end of hemorrhage, but greater than basal levels, while PRA returned to values similar to these at the end of hemorrhage. The decrease in LVP, NE, and E following HSD resuscitation for the treatment of hemorrhagic hypotension may result from and contribute to the rectification of cardiovascular and metabolic function.

Adrenocorticotropic Hormone↗
PubMed1990

Valine, isoleucine, and leucine. A new treatment for phenylketonuria.

Early treatment of phenylketonuria by dietary phenylalanine restriction prevents brain damage. Behavioral and cognitive deficits occur when serum phenylalanine levels increase. Administration of valine, isoleucine, and leucine to patients with phenylketonuria may inhibit entry of phenylalanine into the brain and reduce its toxic effects on the central nervous system. Sixteen adolescents and young adults with phenylketonuria participated in double-blind trials in which a valine, isoleucine, and leucine mixture or a control mixture was given for four 3-month periods. Biochemical and neuropsychologic tests were carried out before and at the end of each period. Time to completion of a test that required substantial attention with mental processing (Attention Diagnostic Method) was faster during the valine, isoleucine, and leucine periods than during the control mixture periods. Improvement with valine, isoleucine, and leucine on a less demanding task (Continuous Performance Test) approached significance. These data lent support to the hypothesis that a regimen of valine, isoleucine, and leucine may help individuals unable to maintain low serum phenylalanine levels.

Adolescent↗
PubMed1990

Superiority of hypertonic saline/dextran over hypertonic saline during the first 30 min of resuscitation following hemorrhagic hypotension in conscious swine.

We compared the effectiveness of intravenously administering hypertonic saline/dextran (HSD; 7.5% NaCl in 6% Dextran-70, n = 6) to hypertonic saline (HS) alone (7.5% NaCl, n = 8) in rectifying detrimental effects of hemorrhage on cardiovascular function. Chronically instrumented conscious swine were hemorrhaged 37.5 ml/kg over 60 min. If untreated, this model is 100% lethal within 60 min. Swine received HSD or HS at 4 ml/kg. Functional variables were measured before and at 5, 15, and 30 min following treatment. HSD produced a significantly greater plasma volume expansion than HS alone (13.6 compared to 9.9 ml/kg). Over 30 min expansion was sustained in pigs receiving HSD but pigs receiving HS regressed. Cardiac index (CI) increased for both treatments, being greater with HSD, 104 ml/kg/min, compared to HS alone, 46 ml/kg/min. Neither group fully sustained these elevated values post-treatment, but remained consistently greater than values after hemorrhage; however, the difference in CI between treatments was maintained. Oxygen delivery showed a trend similar to that of CI. We conclude that resuscitation with HSD is superior to HS in improving cardiovascular function over the first 30 min after hemorrhage.

Animals↗
PubMed1990

Renal responses to graded hemorrhage in conscious pig.

We developed a conscious pig model with a chronically instrumented kidney to measure renal blood flow (RBF), glomerular filtration rate (GFR), and excretory functions during hemorrhage. Seven to 10 days before experimentation, pigs were splenectomized, arterial and venous catheters were implanted, an ultrasonic flow probe was placed on the renal artery, and a pyelostomy was performed for nonocclusively placing a ureteral catheter. Measurements were taken before hemorrhage, and at hemorrhage volumes of 7, 14, 21, and 28 ml/kg (equivalent to 10.5, 21, 31, and 42% of the estimated blood volume), or at corresponding time points for controls. RBF was decreased by 30% when 21% of the blood (14 mg/kg) was removed, before arterial pressure, GFR, or urine flow or excretion was changed. At volumes of hemorrhage greater than 14 ml/kg, there were progressive decreases in RBF, GFR, urine flow rate, osmotic and electrolyte excretion, and arterial pressure. Thus pigs, like humans, respond to hypovolemia with an early redistribution of blood flow away from the kidney.

Animals↗
PubMed1990

Blood gas and acid-base status of conscious pigs subjected to fixed-volume hemorrhage and resuscitated with hypertonic saline dextran.

Conscious, chronically instrumented pigs were subjected to a progressive, fixed-volume hemorrhage (37.5 ml/kg over 1 h) and subsequent resuscitation with 7.5% hemorrhage (37.5 ml/kg over 1 h) and subsequent resuscitation with 7.5% NaCl/6% Dextran 70 (4 ml/kg). Hemorrhage led to increases in arterial PO2, HbO2, plasma lactate, base deficit, and mixed venous PCO2. It led to decreases in arterial PCO2, plasma bicarbonate, and buffer base, as well as mixed venous PO2, HbO2, and pH. These effects were attributable to reduced O2 delivery, lactacidemia, hyperventilation, and hemodilution. Resuscitation with hypertonic saline/dextran produced a transient increase in arterial PCO2 and base deficit and a transient decrease in pH, effects that were attributable to a transfer of venous blood attributes to the arterial circulation. Resuscitation also produced an immediate decrease in arterial buffer base, an effect attributable to hemodilution. Subsequently, over 4 h, most cardiopulmonary and metabolic variables gradually reverted toward control levels, thereby ameliorating the deleterious blood gas and acid-base disturbances produced by severe hemorrhage.

Acid-Base Imbalance↗
PubMed1989

Resuscitation of conscious pigs following hemorrhage: comparative efficacy of small-volume resuscitation.

Efficacy of small-volume resuscitation (4 ml/kg) with 7.5% NaCl in 6% Dextran 70 (HSD), 7.5% NaCl (HS), dextran (D), and 0.9% NaCl (NS) was evaluated in conscious swine bled 37.5 ml/kg over 60 min. Hemorrhage reduced cardiac index (CI), stroke volume (SV), and mean arterial pressure (MAP). Four-hour survival after HSD (67%) was significantly (P less than 0.05) greater than after HS (25%), D (17%), or NS (0%). The superior performance of HSD, and to a lesser extent HS, was associated with rapid plasma volume expansion, improved CI and SV, and decreased heart rate. The acute increases in cardiac index and stroke volume were greater following treatment with HSD and the improvement persisted for 4 hr. HSD also produced a transient increase in MAP. Plasma Na+ concentration and osmolality were increased to a similar extent with HSD and HS, while plasma K+ levels were initially decreased, returning to control levels within 60 min. HSD appears to be a superior small-volume resuscitation solution compared to the other treatments with no detrimental effects.

Animals↗
PubMed1989

Oxygen delivery and demand in conscious pigs subjected to fixed-volume hemorrhage and resuscitated with 7.5% NaCl in 6% Dextran.

A conscious porcine model was used to investigate the adequacy of O2 delivery relative to O2 demand, initially during a fixed-volume hemorrhage (37.5 ml/kg over 1 hr) and subsequently after resuscitation with 7.5% NaCl/6% Dextran 70 (4 ml/kg). Hemorrhage produced a small increase in O2 consumption, severe lactacidemia, and a doubling of apparent O2 demand. These effects were attributable to a behavioral compensation (periodic bouts of muscle activity) which presumably served to improve venous return. Despite enhanced ventilatory function, arterial O2 delivery was markedly reduced by hemorrhage, an effect that was due entirely to decrements in cardiac output and hemoglobin level. The disparity between O2 delivery and O2 demand was lessened following resuscitation with 7.5% NaCl/6% Dextran 70, primarily by suppression of demand and secondarily by an augmentation of delivery.

Animals↗
PubMed1988

Videodensitometric analysis of human coronary stenoses: validation in vivo by intraoperative high-frequency epicardial echocardiography.

Videodensitometry is a nongeometric method of coronary angiographic analysis that can be used to provide an index of coronary luminal area. However, there are few direct studies in vivo of the relationship of videodensitometric data to independent measures of luminal area in humans. Although videodensitometry is theoretically independent of angiographic projection and luminal shape, validation of these assumptions in vivo is also limited. We therefore used intraoperative high-frequency epicardial echocardiography, a technique that can directly determine human coronary luminal area and shape in vivo, to further validate videodensitometry. A total of 36 arterial segments in the left anterior descending and right coronary arteries were studied by videodensitometry and high-frequency echocardiography. Videodensitometry was performed on angiograms in which the arterial segment of interest was not markedly foreshortened and was uniformly filled with contrast. In 22 discrete lesions (13 with circular lumens and nine with oval or complex lumens), videodensitometric and echocardiographic measures of luminal area correlated well (r = .86). In 33 coronary arterial segments, the effect of angiographic projection on videodensitometry was determined by comparison of the results of videodensitometry performed on left anterior oblique vs right anterior oblique angiograms of the segments. Here too, the correlation was good (r = .94, y = 1.04x + 0.002). The good correlation of left anterior oblique with right anterior oblique videodensitometric results held true for lesions with circular and oval or complex lumens. This study further validates the ability of videodensitometry to provide an index of coronary luminal area and confirms in vivo previous assumptions that the results of videodensitometric analysis are independent of angiographic projection and luminal shape.

Adult↗
PubMed1988

Upon-admission adrenal steroidogenesis is adapted to the degree of illness in intensive care unit patients.

Adrenal function was studied in 2 groups of intensive care unit (ICU) patients with varying degrees of illness, as determined by Acute Physiological and Chronic Health Evaluation (APACHE). The 15 seriously ill patients with high APACHE scores (greater than or equal to 25) had elevated Therapeutic Intervention Scores and increased mortality compared to the 15 ill patients (APACHE, less than or equal to 10; 67% vs. 27%). Plasma cortisol, aldosterone, and androstenedione concentrations were increased in the ICU patients compared to those in normal subjects (n = 23), being greater in the seriously ill patients. Plasma dehydroepiandrosterone sulfate (DHEAS) concentrations were low in both groups of ICU patients. The ratios of aldosterone or androstenedione to cortisol were not altered, whereas the DHEAS to cortisol ratios were reduced in the ICU patients. ACTH injection elicited increases in plasma cortisol, aldosterone, and androstenedione concentrations in both groups of ICU patients, and the ratios of aldosterone and androstenedione to cortisol did not change. In the seriously ill patients, plasma DHEAS increased, so that the DHEAS to cortisol ratio did not change, whereas in less ill patients plasma DHEAS did not increase, so that the DHEAS to cortisol ratio was reduced. In this study of patients admitted to an ICU, impairment of adrenal steroid secretion appears to be specific for DHEAS. Although plasma cortisol was elevated in ill patients proportional to the degree of illness, the contribution of the concomitant decrease in DHEAS to this increase is not clear.

Adrenal Glands↗
PubMed1987

Hormonal and renal responses to converting enzyme inhibition during maximal exercise.

The role of angiotensin II in the hormonal and renal responses to maximal exercise was investigated by using the angiotensin-converting enzyme inhibitor captopril. Nine male subjects performed a standardized maximal treadmill test with and without acute captopril treatment (25 mg orally). At rest, captopril elevated plasma renin activity and lowered aldosterone levels. With maximal exercise, captopril treatment reduced the increase in mean arterial blood pressure by 8 mmHg and the increase in plasma renin activity by 3.0 ng ANG I.ml-1.h-1. The responses of adrenocorticotropin (ACTH), cortisol, and vasopressin to maximal exercise were not altered by captopril treatment. Although aldosterone levels were reduced at rest with captopril, during maximal exercise no difference was noted between treatments. Captopril treatment had no effects on the renal handling of salts or water during exercise. In conclusion, angiotensin II plays a role in the increase in mean blood pressure during maximal exercise in normal subjects but has no effect on the exercise responses of ACTH, vasopressin, and aldosterone or on the renal handling of salts and water.

Adrenocorticotropic Hormone↗
PubMed1987

Increased vertebral bone mineral in response to reduced exercise in amenorrheic runners.

Seven female runners found to have exercise-induced amenorrhea and decreased bone mineral were reevaluated after 15 months. During the 15-month period, four runners took supplemental calcium and reduced their weekly running distance by 43%, resulting in an average 5% increase in body weight, increased estradiol levels and eumenorrhea. Bone mineral content increased from 1.003+/-0.097 to 1.070+/-0.089 grams per cm.(2) Three runners continued to have amenorrhea, with no change in running distance or body weight. Estradiol levels remained abnormally low and there was no significant change in the bone mineral content, although all three took supplemental calcium. We found that early osteopenia associated with exercise-induced menstrual dysfunction improved when runners reduced their running distance, gained weight and became eumenorrheic.

Adult↗
PubMed1986

Drinking and subsequent suppression of vasopressin is unaltered by naloxone in dogs.

The effect of the opioid antagonist naloxone on drinking and the subsequent suppression of plasma vasopressin were evaluated in seven dogs following 24 hr of water deprivation. Each animal underwent an intravenous injection of vehicle as a control and a low (0.05 mg/kg) and high (1 mg/kg) dose of naloxone. Plasma vasopressin was significantly (p less than 0.05) increased from a control value of 4.6 +/- 1.9 microU/ml to 9.9 +/- 3.1 microU/ml after the high dose of naloxone. Fluid intake was not altered by naloxone; 42 +/- 6 ml/kg for the control, 45 +/- 8 ml/kg at the low dose, and 49 +/- 7 ml/kg for the high dose. Six minutes after the onset of drinking vasopressin was reduced by 48% for the control, 41% for the low dose and 45% for the high dose, with no significant difference among treatments. Thus, in dehydrated dogs naloxone presumably blocks endogenous opioids, elevates vasopressin following dehydration, but does not affect drinking behavior or the subsequent suppression of vasopressin after drinking.

Animals↗
PubMed1985

Plasma aldosterone and renal function in runners during a 20-day road race.

To evaluate the effects that repeated long-distance running has on plasma aldosterone concentration and urinary excretion of solutes, fifteen male runners were studied during a 20-day, 500-km road race. Venous blood samples were taken on day 1 prior to running, on day 11 after 10 days of running, on day 13 after a 70-h rest, and on day 18 after an additional five days of running. Overnight urine samples were obtained on day 10 before and after running and on days 11, 12, and 13 during the 70-h rest period. Plasma sodium concentrations on days 13 and 18 and plasma potassium concentrations on days 11 and 13 were decreased (P less than 0.05). Plasma aldosterone levels were increased on days 11 and 18 after running and returned to pre-race levels on day 13 after 70 h of rest. Plasma cortisol concentrations were not altered. The urinary excretion rates of sodium were elevated and of aldosterone were decreased after 70 h of rest. Increase in excretion rate of urinary sodium correlated with decrease in concentration of plasma aldosterone. These findings show that plasma aldosterone levels are chronically elevated with repeated long-distance running, resulting in a decrease in urinary excretion rate of sodium.

Adult↗
PubMed1985

Preliminary support for the oral administration of valine, isoleucine and leucine for phenylketonuria.

Recent behavioral data have demonstrated the importance of maintaining low phenylalanine concentrations beyond early childhood in patients with phenylketonuria, which can be a difficult task, particularly during adolescence. Administration of certain large neutral amino-acids (valine, isoleucine, leucine--VIL) appears to reduce phenylalanine concentrations in the cerebrospinal fluid of humans and in the brain of rats. The present study compared neuropsychological test-performance of six patients with phenylketonuria during periods of VIL administration and periods when this supplement was not given. Although individual responses to VIL were variable, there was an over-all improvement of about 1 1/2 SD in neuropsychological test performance during VIL treatment. Abstract reasoning and tactile motor problem-solving increased more than pure motor performance.

Adolescent↗