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Biomedical subjects

G M Vaughan

Publications and source records attributed to G M Vaughan.

At least 55 records · Page 3Linked to original sources
PubMed1986

Human melatonin in physiologic and diseased states: neural control of the rhythm.

The human melatonin rhythm is endogenous with a surge of secretion entrained to the dark part of the cycle. Reports show consistent blunting or blockade of this nocturnal surge in the presence of sympathetic neurologic lesions and after administration of beta-adrenergic antagonists. However, there is remarkable resistance to elevation of daytime melatonin secretion by adrenergic agonists and by conditions of general sympathetic hyperactivity. Analysis of these and other reports together with results in lower animals allows insight into the control of the human melatonin rhythm. This rhythm is driven by a neural pathway to the pineal gland similar to that in animals and includes the sympathetic nervous system acting through a beta-adrenergic mechanism. Sympathetic control of the pineal is exerted independently of general sympathetic function, with sympathetic information partitioned separately for the pineal. The pineal is protected from humoral and exogenous adrenergic agents, in part by a nerve ending reuptake mechanism which has been demonstrated in rats and hamsters. Results in Syrian hamsters also suggest that sensitivity of the pineal to norepinephrine appears only at night. Melatonin production is an index, not of general sympathetic activity, but of the activity in a specific pathway and provides a stable humoral signal reflecting light/dark exposure. Observations of reduced melatonin values as a function of puberty, age, and depressive illness are not yet understood in the context of a unitary explanation of pineal function but indicate interesting frontiers in this field.

Adult↗
PubMed1985

Nonthyroidal control of metabolism after burn injury: possible role of glucagon.

The endocrine basis for control of metabolism in nonthyroidal illness is not yet understood. Burn injury is associated with reduced serum concentrations of thyroid hormones and with resting hypermetabolism. One index of severity is total burn size (TBS, % body surface). After overnight fasting and recumbency, resting metabolic rate (MR, O2 consumption) was measured weekly and plasma was sampled for determination of glucose, total cholesterol, triglycerides, insulin, glucagon, somatostatin, growth hormone, norepinephrine, epinephrine, and cortisol in 28 burned men, 17-23 years old, TBS 2%-85%, including 8 controls with minimal injury (TBS less than or equal to 7.5%). MR was elevated in proportion to burn size mainly in the first week then declined toward normal. Growth hormone was not changed. Two multiple regression analyses (validated by random partitioning of data) determined which plasma variables independently reflected residual variation in MR: without TBS entered as a variable, high MR was associated with elevated glucose, cortisol, and glucagon, and low cholesterol (cumulative r2 = 0.79); with TBS entered, high MR was associated with greater TBS, elevated norepinephrine, and again high glucagon and low cholesterol (r2 = 0.81). Resting metabolism after burn injury is controlled not by the thyroid but may be controlled by a set of antiinsulin hormones that does not include growth hormone, but possibly includes glucagon.

Adolescent↗
PubMed1985

Reduced serum T4 and T3 and their altered serum binding after burn injury in rats.

Total T4 and T3 concentrations are often suppressed in burned patients. To investigate the significance of such changes, we have characterized serum T4 and T3 after full-thickness scald burns (60% body surface under anesthesia) of 270-gm male Sprague-Dawley rats housed in a light:dark cycle of 14:10 hr. Groups (N = 9-15) of BURN, SHAM (anesthesia, fur clipped, no burn) and CON (controls) were sacrificed on postburn days 8 and 14. T4 and T3 (radioimmunoassay), free indices (FT4I and FT3I = respective total T4 or T3 X in vitro charcoal T3 uptake, T3U), and free concentrations (FT4 and FT3 = total T4 or T3 X respective equilibrium dialyzable fraction, T4DF or T3DF) were not different between CON and SHAM. Compared to SHAM, mean T4 and FT4I (by about 48% of respective SHAM means on both days), TT3 (by 36, 43%), and FT3I (by 38, 45%) (days 8, 14) were suppressed in BURN (all p less than 0.001). T4DF (both days) and T3DF (day 14) were significantly elevated in BURN, demonstrating a deficit in serum binding, but T3U was not. FT4 (by 26, 22%) and FT3 (by 33, 34%) (day 8, 14) were significantly lower in BURN. On either day, covariance analyses (BURN vs. combined CON + SHAM) correlated FT4I or FT3I with respective FT4 or FT3 (all p less than 0.001, slopes not different in BURN vs. CON + SHAM), but the lower FT4I and FT3I in BURN significantly overestimated (all p less than 0.001) the depression of respective FT4 and FT3 in BURN.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1985

Pineal function in burns: melatonin is not a marker for general sympathetic activity.

Burn injury in humans or rats is a model of marked elevation of general sympathetic activity for weeks, manifested in part by increased heart rate, metabolic rate, core temperature, and plasma and urinary catecholamines. Plasma melatonin was sampled at 2-h intervals for 24 h in 9 control subjects and 11 patients with severe burn injury. Daytime melatonin was not different between the groups, but nighttime values were significantly lower in the burn patients. A nocturnal surge was still significant in the patients. Resting heart rate and rectal temperature were elevated in the burn patients. In male Sprague-Dawley rats, pineal melatonin content did not differ between controls and those with an experimental burn at 4 h into the light phase nor during the nocturnal surge. Male Syrian hamsters with burns had lower daytime pineal melatonin content than did controls, but the nocturnal surge in pineal melatonin was not significantly different between groups, nor was daytime morning serum melatonin. Sympathetic activity appears partitioned, with that controlling melatonin (nocturnal surge) regulated independently. In agreement with our previous findings in other models, melatonin is not a marker for general sympathetic activity, even following severe burn injury.

Adult↗
PubMed1985

Pineal-induced depression of free thyroxine in Syrian hamsters.

Blind hamsters had no alteration of the dialyzable fraction of serum thyroxine (T4) but had depressed total and free T4 concentrations compared to controls. Prevention of the effects of blinding by pinealectomy indicates pineal influence on circulating free T4 concentration. Parallel changes in free T4 and the free T4 index indicate adequacy of the index in representing pineal-induced changes in free T4.

Animals↗
PubMed1985

Hormonal changes in burned hamsters.

Burned male Syrian hamsters (burn size 23% of body surface) exhibited reduced total (T4) and free (FT4) serum concentrations, a defect in T4 binding to serum proteins manifested by the T4 dialyzable fraction but not the in vitro T3 charcoal uptake, and reduced serum testosterone concentration. These changes are similar to those noted previously in burned humans. Unlike such patients, burned hamsters did not exhibit reduced serum T3 nor elevated rT3 concentrations in a reproducible manner. Pinealectomy performed before burning in hamsters did not prevent the burn-induced depression in serum T4 and testosterone.

Animals↗
PubMed1985

Alterations of mental status and thyroid hormones after thermal injury.

In 16 burn patients, mean values for serum T4 and T3, their T3 uptake-derived free indices (FT4I and FT3I) and dialysis-derived free concentrations (FT4 and FT3) were depressed (all P less than 0.001) compared to respective means in 13 normal subjects. In the patients, the free hormone indices were relatively more depressed below control values than were the free hormone concentrations. However, within the group of burn patients, variation in FT4I reflected that of FT4 (r = 0.91), and variation in FT3I reflected that of FT3 (r = 0.93). We then studied serum T4, T3, and their free indices in 134 patients (burn size, 6-96% of the skin area), including 45 nonsurvivors, none of whom received steroid, dopamine, or iodine treatment. At each sampling, the level of obtundation (LO) was determined on a 6-point scale from normal to deep coma. Whereas initially low mean FT4I values rose in survivors, they remained lower in nonsurvivors than in survivors until death in the nonsurvivors. In nonsurvivors, mean LO worsened in the first week and remained worse than that in survivors until death. Multiple regression analyses showed that for a given age or burn size, nonsurvival was better correlated with lower T4 or FT4I than with T3 or FT3I, but was even more closely correlated with worse LO (P less than 0.001). Exclusion of data obtained within 24 h of narcotic or tranquilizer doses did not weaken the relationship of nonsurvival with LO and FT4I. Nonsurvival after burn injury was associated with reduced T4, FT4I, and mental status for up to weeks before death, this association being independent of treatment with drugs acting on mental status or thyroid function.

Burns↗
PubMed1984

Replacement therapy with modified immunoglobulin G in burn patients: preliminary kinetic studies.

Suppression of serum immunoglobulin G for periods ranging from days to weeks following thermal injury may enhance the risk of infection in burn patients. In an initial trial, we attempted to determine whether intravenous pulses of Immunoglobulin G (IgG) will establish and maintain normal serum IgG concentrations in this interval. The levels of endogeneous serum IgG in eight control patients, mean total burn size 45 percent body surface area (no IgG infusions), were measured by radial immunodiffusion on various postburn days. Commercially available reduced alkylated IgG (5 percent Gamimune, Cutter Biological, Berkeley, California) was infused in doses of 500 mg/kg twice per week in four patients (total burn size 32 percent) and once per week in five patients (total burn size 47 percent), beginning during the first postburn week. Circulating IgG was measured prior to each infusion and at three postinfusion times: (1) 15 minutes (peak), (2) one day, and (3) either day 3, 4, or 6. Surgery or blood transfusions prior to one of these time points invalidated kinetic analysis of some infusions. Exponential two-point decay constants for total serum IgG after each of 24 infusions were calculated separately for early (day 0-1) and later (day 1-3 or 1-4) postinfusion intervals and assessed by stepwise regression analysis to determine sources of variation in decay. Early decay was seen to be faster with larger burn size after accounting for variation of decay with preinfusion and peak IgG values. Later decay was not related to burn size. Maltose, a constituent of the IgG preparation, was detectable in serum for only four to eight hours after each infusion and may have contributed to a 20 percent increase in total serum glucose between four and eight hours postinfusion. Mean serum IgG in patients given infusions twice weekly was in the normal range after one infusion, about a week earlier than in untreated patients. Such infusions maintained normal IgG levels.

Agammaglobulinemia↗
PubMed1984

Opioid and dopamine involvement in prolactin release induced by arginine vasotocin and vasopressin in the male rat.

The potential involvement of the endogenous opioid and dopamine (DA) systems in the mechanism(s) mediating arginine vasotocin (AVT)- and arginine vasopressin (AVP)-induced prolactin (PRL) release was investigated in vivo. The injection of AVT (5 micrograms) into unanesthetized male rats resulted in a 2-fold stimulation of PRL release 15 min later, followed by an inhibition of PRL release 30 min thereafter; both the stimulatory and inhibitory PRL responses to AVT were obviated by naloxone (NAL) (200 micrograms). Similarly, the administration of either AVT or AVP (5 micrograms) to urethane-anesthetized rats led to a 3- and 5-fold increase in plasma PRL levels, respectively, 10 min after injection. The PRL stimulatory response to both peptides was completely blocked by pretreating the animals with apomorphine (APO) (5 mg); however, the injection of APO by itself had no effect on PRL secretion in these animals. Both AVT and AVP were also effective in stimulating PRL release 10 min after injection in estrogen (50 micrograms)-progesterone (25 mg) (EP)-treated rats anesthetized with urethane. APO negated the PRL stimulatory response to these compounds in the EP-treated rat as well. Normal, urethane-treated rats experienced a 7- to 8-fold increase in PRL levels 20 min following the injection of methysergide (MET) (250 micrograms). Both AVT and AVP caused approximately a 2.5-fold greater PRL response in MET-treated animals than in AVT and AVP controls, respectively; however, only in the MET + AVT-treated rats was the PRL stimulatory response greater than in the MET controls. MET probably stimulated PRL through its DA antagonistic properties.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1984

Effects of injections and/or chronic implants of melatonin and 5-methoxytryptamine on plasma thyroid hormones in male and female Syrian hamsters.

Plasma thyroid hormone concentrations in male and female Syrian hamsters were evaluated in five experiments after two pineal indoles, melatonin (MEL) and 5-methoxytryptamine (5-MT), were administered as chronic s.c. implants and/or daily afternoon injections. Circulating concentrations of thyroxine (T4), ordinarily maintained by the long photoperiod (LD 14:10), were inhibited by daily afternoon injections of 25 micrograms MEL but not 5-MT in male (experiment 1) and female (experiment 2) Syrian hamsters. The suppressive effect of MEL injections on T4 concentration in the long photoperiod was prevented in both sexes by a s.c. beeswax pellet containing either 1 mg MEL or 5-MT. In the third experiment, various doses of MEL or 5-MT were injected each afternoon for 12 weeks to compare the effectiveness of these two indoles in reducing T4 concentrations in hamsters maintained in the long photoperiod. Only the highest dose (200 micrograms) of 5-MT effectively suppressed T4 concentrations whereas all doses of MEL (greater than or equal to 5 micrograms) significantly reduced plasma T4. MEL or 5-MT (1-1,000 micrograms) were implanted in beeswax pellets in male hamsters exposed to short photoperiod (LD 10:14) to determine if either indole could prevent the short photoperiod-induced suppression of T4 (experiments 4 and 5). Regression and covariance analyses showed a significant log dose-related elevation of T4 in these hamsters, indicating equal potency of MEL and 5-MT in preventing the short photoperiod-induced suppression of T4. 5-MT given by either injection or implantation raised plasma triiodothyronine (T3) in female (experiment 2) but not in male hamsters.(ABSTRACT TRUNCATED AT 250 WORDS)

5-Methoxytryptamine↗
PubMed1983

Inappropriate vasopressin secretion (SIADH) in burned patients.

To determine if concentration of plasma arginine vasopressin (AVP) is inappropriate for the plasma Na+ concentration in hyponatremic burned patients, we obtained 32 plasma samples from 20 patients with total burn size (TBS) 15 to 80% of body surface on or after postburn day (PBD) 4 in the morning following all-night recumbency. In the 25 samples (17 patients) with hyponatremia, AVP was elevated, 1.6 to 14.3 (normal less than 0.5) pg/ml. Most patients with normal serum Na+ had normal AVP values. Out of the total, nine patients (12 samples) without renal failure or sepsis, selected also for hyponatremia and urinary Na+ greater than or equal to 20 mEq/L, were considered separately. BUN of 11.7 +/- 1.8 mg/dl and plasma glucose of 130 +/- 5.6 mg/dl, Na+ of 130 +/- 1.1 mEq/L, calculated osmolality of 272 +/- 1.6 mosm/kg, and cortisol of 20.4 +/- 1.6 micrograms/dl were associated with a 24-hour fluid intake of 4.3 +/- 0.26 L and urinary output of 2.7 +/- 0.33 L, Na+ of 80 +/- 14 mEq/L, and osmolality of 520 +/- 73 mosm/kg (mean +/- SE). In all of the plasma samples, AVP was markedly elevated (6.9 +/- 1.1 pg/ml). In another study, four hyponatremic burned patients were given a standard water load. Excretion of the water was delayed, and further dilution of the initially hypotonic plasma resulted in a fall of urinary osmolality and plasma AVP. Cutaneous thermal injury can cause resetting of the mechanism linking plasma tonicity and AVP secretion resulting in dilutional hyponatremia. This syndrome occurs in the absence of gross physiologic perturbations such as volume depletion or adrenal insufficiency.

Adolescent↗
PubMed1982

Hypermetabolic low triiodothyronine syndrome of burn injury.

The free tetraiodothyronine index (FT4I) and free triiodothyronine index (FT3I) in burn patients represented the serum levels of free (dialyzable) T4 and free T3, respectively. FT4I and FT3I were lower with greater burn size and were lower in nonsurvivors than expected for the burn size. there was no compensatory elevation of basal or releasing hormone-stimulated thyrotrophin (TSH) concentrations. Reverse T3 was higher with greater burn size. T3 treatment restored FT3I but did not affect mortality or resting metabolic rate (MR) measured in survivors, compared with placebo therapy. Whereas the hypermetabolic response to burn injury appeared t be independent of thyroid hormones, MR was correlated positively with burn size and with elevated plasma norepinephrine and epinephrine concentrations for several weeks after injury. Lack of augmented TSH concentrations, absence of low plasma reverse T3, and presence of hypermetabolism suggest that the reduced plasma free T3 does not indicate functional hypothyroidism, but may represent an adaptation to the assumption of metabolic control by the sympathetic nervous system.

Adolescent↗
PubMed1982

Cortisol and corticotrophin in burned patients.

In a study of 36 men burned in a fire, based on sequential early morning samples, plasma cortisol concentration was elevated in proportion to burn size. Plasma corticotrophin (ACTH) was not correlated with burn size, suggesting that factors other than ACTH contribute to the elevated cortisol. Cortisol levels did not fall on the days preceding death in nonsurvivors. During 24-hr sampling, burned patients exhibited a fitted cortisol curve mean that was elevated in proportion to burn size, a rhythm amplitude that was significantly less than that in uninjured controls, and a normal peak time. Metabolic rate, rectal temperature, and urinary catecholamine excretion were also elevated in proportion to burn size. Although plasma cortisol was positively correlated with metabolic rate and with temperature, this appeared to result from a common relationship of these variables with burn size. On the other hand, urinary catecholamine values significantly reduced the residual variance of metabolic rate and temperature after accounting for variance related to burn size. Cortisol appears to be less prominent than catecholamines as a possible mediator of the elevated thermogenesis.

Adolescent↗
PubMed1982

Thyroid hormones in male hamsters with activated pineals or melatonin treatment.

Blinding resulted in gonadal and prostatic atrophy and reduced plasma thyroxine (T4), free T4 index (FT4I) and reverse triiodothyronine (rT3) levels in adult male hamsters housed in light-to-dark, 14:10 h. Similar effects were seen after daily evening injections of 25 microgram melatonin. Pinealectomy prevented the effects of blinding or melatonin injections. There were no pineal- or melatonin-induced decrements in T3 or thyrotrophin (TSH) concentrations. TSH was elevated by blinding in one experiment but not in another, despite suppression of T4 and FT4I in both. Orally administered melatonin (approximately 245 microgram daily in drinking water through the evening and night) reduced the weight of testes and prostates and slightly lowered plasma T4 and FT4I, indicating the effectiveness of melatonin by this route. The capability of the pineal and of melatonin to suppress plasma T4 is not a result of sex-steroid-induced alteration of plasma binding but is most likely a result of variable suppression of the pituitary-thyroid axis at the level of TSH regulation and also at the level of T4 secretion and/or metabolism. Reduced rT3, but not T3 levels after blinding, may reflect the pineal-induced deficit in T4 as a substrate for rT3 formation, altered peripheral conversion of T4 or altered disposal of thyroid hormones.

Animals↗
PubMed1981

Age-associated reduction in nocturnal pineal melatonin levels in female rats.

Pineal N-acetyltransferase (NAT) activity and radioimmunoassayable levels of melatonin were compared in 2-month-old (young), 12-month-old (middle-aged), and 29-month-old (old) female rats killed at 1600 h (during the light) and at 2300 h (4 h after darkness onset) and 0100 h (6 h after darkness onset). During the light period, NAT levels were equivalent in pineals from each age group. With the onset of darkness NAT levels rose sharply and were again equivalent in all groups at 2300 h. At 0100 h pineal NAT values in the old rats were lower than in the other two groups. Melatonin values were low in pineal glands of all animals killed at 1600 h in light. By 4 h after darkness onset pineal melatonin content in the young rats had increased 12-fold compared to a 6-fold rise in the old animals. Melatonin levels in the middle aged rats were intermediate between the other two groups. Similar relationships were observed in the rats killed at 0100 h. By this time the young rats had melatonin levels 17 times higher than during the day while the increase in the old rats was only 7-fold; 12-month-old rats again had intermediate levels. The finding show a marked reduction in pineal melatonin with aging in female rats.

Aging↗
PubMed1980

Influence of pinealectomy on corticotropin (ACTH).

Sensory deprivation produced by removing the eyes and olfactory bulbs in male rats allowed pinealectomy to markedly augment the post-adrenalectomy elevation of ACTH levels. Pineal removal or sensory deprivation separately did not have this effect. Thus, intact sensory input and an intact pineal gland are independently capable of restricting the post-adrenalectomy rise in ACTH levels.

Adrenocorticotropic Hormone↗
PubMed1980

Plasma norepinephrine, epinephrine, and thyroid hormone interactions in severely burned patients.

In this prospective study of thyroid catecholamine interactions, 15 severely burned patients were divided into two groups. Nine patients receiving 200 micrograms/day of triiodothyronine constituted the T3-treated group. Eight additional patients constituted the untreated group. Mean serum concentrations of T3 were significantly lower in the untreated group than in the treated group. Mean serum thyroxine (T4) concentrations were significantly higher in the untreated group than in the treated group. The mean plasma norepinephrine concentration in the untreated group was significantly greater than that of the treated group. In the untreated group, log plasma norepinephrine correlated inversely with serum T3. Similarly, in the untreated group, log plasma epinephrine correlated inversely with serum T3. Metabolic rates were not different between groups. These data suggest that a reciprocal relationship exists between plasma concentration of T3 and both norepinephrine and epinephrine in untreated burn patients and that treatment with the metabolically active hormone, triiodothyronine, does not alter the level of hypermetabolism accompanying thermal injury.

Adult↗