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Biomedical subjects

R W Hamill

Publications and source records attributed to R W Hamill.

At least 37 records · Page 2Linked to original sources
PubMed1990

The adrenocortical response to brain injury: correlation with the severity of neurologic dysfunction, effects of intoxication, and patient outcome.

To test the hypothesis that cortisol levels reflect the extent of neurologic dysfunction and predict patient outcome, neurologic function and cortisol levels were determined in 120 traumatically brain injured patients who never received glucocorticoid treatment. Their mean age was 29 years and 78% were men. The impact of intoxication was examined in 59 patients who had ethanol levels measured. Ethanol was detectable in 40 patients and greater than or equal to 100 mg/dl in 31. There were significant correlations between the extent of neurologic dysfunction, determined by the Glasgow Coma Score and plasma cortisol concentrations 1 and 4 days postaccident. Cortisol levels were universally elevated on admission and approached normal 7 days later. Multiple linear regression analysis revealed significant effects of circulating ethanol levels on the association between cortisol concentrations and progressively worsening neurologic function, i.e., ethanol reduced the magnitude of the cortisol elevations in a dose dependent manner, abolishing this relationship at levels above 100 mg/dl. Analysis of the relationships between circulating cortisol levels and patient outcome provided a second method for ascertaining the association between injury severity and the magnitude of adrenocortical activation. Admission and day 1 cortisol concentrations were 25 to 40% lower in patients having good recoveries or moderate disabilities than those who remained severely disabled, persistently vegetative or died; serum cortisol values of less than 20 micrograms/dl one day after the accident were more likely to be associated with a good outcome than a poor one (55 vs. 25%, p less than 0.001). The worsening prognosis of patients having higher cortisol values is further reflected in the duration of acute hospitalization of these individuals.(ABSTRACT TRUNCATED AT 250 WORDS)

Accidents, Traffic↗
PubMed1989

The ontogeny of substance P- and serotonin-like immunoreactivities in the sexually dimorphic cremaster nucleus of the rat spinal cord.

This study investigates the ontogeny of two transmitter systems which innervate the sexually dimorphic cremaster nucleus (CN). Since these transmitter systems arise from separate extra- and intraspinal sources, their ontological sequences differ. In males, substance P (SP) innervates CN motoneurons on postnatal day (P) 0, while serotonin (5-HT) is first observed on P2. SP reaches a mature innervation pattern on P20, while 5-HT maturation is prolonged to P40-60. It is suggested that part of the reason for the differing rates of development of 5-HT and SP within CN is due to the source of the innervating fibers; 5-HT descends from the brainstem while SP is of intraspinal origin. On P6, the SP innervation of the dorsal processes of the male CN is so advanced that the spinal cord may be 'sexed' according to the male presence, or the female 'absence', of this SP pattern. In developing and adult females, the 5-HT innervation of the CN is greater than the SP innervation. In addition, the 5-HT and SP innervation of the female CN is greater than the surrounding motor columns. Compared to surrounding ventral gray horn motor nuclei, the CN receives a slightly delayed SP and 5-HT innervation and this may be a reflection of the postnatal formation of the cremaster muscle.

Animals↗
PubMed1989

Parasympathetic nerves in penile erectile tissue of the rat contain choline acetyltransferase.

Choline acetyltransferase (ChAT), a biochemical marker of cholinergic neurons, was measured in the erectile tissue of intact rats and in rats in which postganglionic fibers from the pelvic plexus were interrupted. ChAT activity in the denervated erectile tissue fell by 56% compared to control tissues. Acetylcholinesterase positive (AChE+) nerves also fell by about 48%. Penile neurons distal to the lesion probably account for the residual ChAT activity and remaining AChE+ nerve fibers in erectile tissue. These results indicate that acetylcholine is an important neurotransmitter in the regulation of penile erection.

Animals↗
PubMed1989

Organizational role of testosterone on the biochemical and morphological development of the hypogastric ganglion.

Previous reports have demonstrated that after postnatal day 10 testosterone influences hypogastric ganglion (HG) development by 'activating' morphological and biochemical indices. We now report an 'organizational' influence on the developing HG during the first 10 postnatal days. To investigate the organizational effects of testosterone, male rats were castrated within 12 h of birth. Testosterone replacement therapy initiated following castration maintained the normal number of neurons in the HG. Conversely, delayed replacement therapy starting at day 10 or vehicle treatment only, resulted in a significant decrease in neuron number. Castration also produced a significant decrease in somal and nuclear cross-sectional areas. Testosterone replacement, whether initiated immediately or if delayed until day 10, restored somal and nuclear cross-sectional areas to normal. Tyrosine hydroxylase (TH) and choline acetyltransferase (ChAT) activities were sensitive to both testosterone dosage and the time of administration. Testosterone decanoate administered subsequent to castration was not able to completely reverse the enzyme activity deficits, while delayed replacement therapy was even less effective in restoring enzyme activities. In contrast, higher doses of testosterone completely reversed enzyme activity deficits, and in fact produced a significant increase in TH activity. Again, delayed testosterone replacement did not fully restore deficits in enzyme activity. In summary, the hormonal environment during the first 10 days of life is critical for the organization of HG cell number; in contrast, nuclear and cell size appear to be dependent on testosterone for activation. TH and ChAT activities also appear to be organized during this dose- and time-dependent developmental period.

Adrenergic Fibers↗
PubMed1989

Hypogastric ganglion perinatal development: evidence for androgen specificity via androgen receptors.

The hypogastric ganglion (HG) has previously been shown to be sensitive to both the organizational and activational influences of testosterone. The current investigations examined whether testosterone exerts similar effects prenatally, whether these events are specifically controlled by androgen, and whether androgens might directly masculinize the HG. Prenatal treatment with an anti-androgen, flutamide, resulted in significant decreases in the adult levels of tyrosine hydroxylase (TH) activity, an index of postsynaptic noradrenergic ontogeny, and choline acetyltransferase (ChAT) activity, a marker for presynaptic terminal formation. In addition, testosterone propionate and dihydrotestosterone benzoate reversed the effects of neonatal castration on the development of TH and ChAT activities. In contrast estradiol benzoate was unable to restore enzyme activities. To determine whether the above observations might be produced by direct effects on the HG, androgen cytosol receptor characteristics were studied. Competition and saturation analyses demonstrate that the affinity and specificity of the androgen cytosol receptor in the HG are similar to that displayed in the pituitary, which has previously been shown to contain androgen receptors. These results suggest that the adult levels of TH and ChAT activities are organized during prenatal and early postnatal development. In addition, the organization of the HG appears to be androgen specific. The presence of cytosol androgen receptors suggests that the organizational effects of androgens are possibly induced by a direct mechanism.

Adrenergic Fibers↗
PubMed1989

Target regulation of the serotonin and substance P innervation of the sexually dimorphic cremaster nucleus.

The effects of perinatal castrations on the serotonin (5-HT) and substance P (SP) innervation patterns of the adult male cremaster nucleus (CN) were examined in Sprague-Dawley rats. These investigations reveal that day-of-birth bilateral castration precludes cremaster muscle formation, significantly reduces CN motoneuron number, and dramatically reduces the 5-HT and SP innervation of the adult male CN. Day-of-birth castration reduces the adult CN SP innervation pattern to a greater degree than the 5-HT pattern and this may be attributed to a substantial loss of primary afferent information to the dorsal horn of the spinal cord. Furthermore, day-of-birth unilateral castration causes an ipsilateral reduction in the adult 5-HT and SP immunostaining patterns. This may be correlated with the failure of the ipsilateral cremaster muscle to form with a subsequent ipsilateral reduction of CN motoneuron number. On the contralateral side the intact testis is accompanied by normal cremaster muscle gross morphology, CN motoneuron number, and CN immunostaining. Together these observations suggest that the sexually dimorphic 5-HT and SP innervation of the male CN is predominantly under target control vs androgen control. Castration during adulthood does not alter the 5-HT and SP innervation patterns of CN; thus, a time-dependent period, probably initiated by cremaster muscle formation, underlies these target organ regulatory effects.

Animals↗
PubMed1989

Postnatal ontogeny of enkephalin fibers in spinal sympathetic nuclei.

The postnatal distribution of enkephalin (Enk) fibers is described in preganglionic containing sympathetic nuclei in the rat thoracolumbar spinal cord. In high thoracic spinal cord, at birth, Enk fibers are present in moderate numbers in the intermediolateralis nucleus, pars principalis (ILp), and nucleus intercalatus spinalis (IC). Enkephalin fibers first appear in the dorsal commissural nucleus (dcn) on postnatal day 2. Postnatal day 6 represents a pivotal timepoint when the basic Enk innervation pattern is established. From postnatal day 11 through day 20 there is a gradual accumulation of Enk fibers within each of the sympathetic nuclei such that the density and distribution of immunoreactive fibers approaches the adult appearance by postnatal day 20. An adult pattern is achieved by postnatal day 30. There is a rostral-caudal gradient in the developmental appearance of Enk fibers in sympathetic nuclei such that the ILp nucleus contains Enk fibers on postnatal day 0 in the high thoracic spinal levels compared to postnatal day 6 in low thoracic-high lumbar spinal levels. Examination of the location of Enk fibers during ontogeny highlighted several additional features of the distribution of Enk fibers in the adult animal. Enkephalin fibers delineate two subdivisions of the IC nucleus; a thin dense core of Enk fibers contained within a broader band of moderate numbers of Enk fibers. We also report variations in the general overall pattern of the Enk fiber distribution in high thoracic, middle thoracic, and lwo thoracic-high lumbar spinal cord levels.

Adrenergic Fibers↗
PubMed1989

Immunohistochemical distribution of serotonin in spinal autonomic nuclei: I. Fiber patterns in the adult rat.

The differential distribution of serotonin (5HT) fibers in spinal laminae VII and X is described for the adult rat. The results indicate that descending 5HT fibers preferentially innervate those regions of lamina VII that contain sympathetic and parasympathetic neurons. In lamina X, especially the dorsal commissural nucleus, large numbers of 5HT fibers are observed throughout the spinal cord. Moreover, sympathetic nuclei are more richly innervated with 5HT than the spinal parasympathetic nuclei. Spinal cord hemisections reveal that spinal autonomic nuclei are differentially innervated: ipsilateral serotoninergic projections to the intermediolateral cell column are preferentially interrupted. In addition, a large crossed 5HT projection exists throughout the length of the spinal cord that decussates five to six spinal segments rostral to its termination. Both crossed and uncrossed 5HT fibers span many spinal segments and have large numbers of collaterals. Spinal cord transections show that the vast majority of spinal 5HT descends from the brainstem but that some 5HT fibers are of intrinsic origin.

Animals↗
PubMed1989

Immunohistochemical distribution of serotonin in spinal autonomic nuclei: II. Early and late postnatal ontogeny in the rat.

These studies reveal that the postnatal ontogeny of serotonin (5HT) in the sympathetic nuclei of the rat spinal cord is protracted; the adult complement of 5HT-immunoreactive fibers is not achieved until at least 60 days of age. As descending serotonin fibers innervate and demarcate the distribution of preganglionic sympathetic nuclei, rostral-caudal and temporal gradients exist. Additionally, a heterogeneous segmental 5HT ontogenetic pattern is observed in sympathetic nuclei. Most serotonin fibers in laminae VII and X are unorganized at birth except for some sympathetic nuclei in high thoracic regions where the 5HT sympathetic pattern is being initiated. By postnatal day 6 the framework of the 5HT pattern is established in all sympathetic nuclei, and by postnatal day 16 a pattern is formed, which develops into the compact adult state by postnatal day 60. The protracted period of sympathetic 5HT development corresponds with the length of time it takes for the autonomic nervous system to mature. In addition, 5HT intraspinal cell bodies are observed at all time points examined, except for the day of birth, and are found in the same regions as adult 5HT neurons, i.e., dorsal or lateral to the central canal in laminae VII and X and in all spinal segments except cervical levels. Many of the 5HT neurons are pericanalicular and bipolar in appearance. Multipolar 5HT neurons are first observed on postnatal day 45.

Aging↗
PubMed1989

Androgen-specific critical periods for the organization of the major pelvic ganglion.

Previous studies indicate that the major pelvic ganglion (PG) is dependent on testosterone for normal development. Tyrosine hydroxylase (T-OH), DOPA decarboxylase, and choline acetyltransferase (CAT) activities are significantly reduced by postnatal castration on day 10-11, while testosterone replacement therapy reversed all developmental enzyme activity deficits (Melvin and Hamill, 1987). In the present studies castration on the day of birth combined with various testosterone-replacement paradigms produced effects demonstrating that the PG is sensitive to testosterone dosage and time of administration during early postnatal development. Gonadal hormone replacement experiments show that the androgens testosterone and dihydrotestosterone were effective in restoring T-OH and CAT activity deficits produced by neonatal castration. Estrogen therapy reversed the deficits in CAT activity, but was ineffective in reversing the alterations in T-OH activity. Treatment of pregnant dams with the anti-androgen flutamide altered the ontogeny of T-OH and CAT activities in pups despite replacement therapy on the day of birth. Thus, androgen-critical periods exist prenatally as well as postnatally. These studies suggest that the organization of PG development is critically dependent on both the time of exposure and dose of testosterone. Prenatal and postnatal critical periods appear to exist. In addition, the lack of an effect of estradiol on tyrosine hydroxylase activity suggests that androgens are specifically responsible for organizing the noradrenergic development of the PG.

Androgens↗
PubMed1988

The postnatal ontogeny of substance P-immunoreactive fibers in the sympathetic preganglionic nuclei of the rat.

The ontogeny of substance P (SP)-containing fibers and puncta is described in laminae VII and X of the rat thoracolumbar spinal cord from the day of birth until postnatal day (P) 60. As SP fibers and puncta innervate and demarcate the distribution of preganglionic sympathetic nuclei, strong temporal and weak rostrocaudal ontogenetic gradients exist. Additionally, a heterogeneous segmental SP ontogenetic pattern is observed in sympathetic nuclei. On the day of birth, SP fibers are present in an unorganized fashion in sympathetic nuclei with the exception of the nucleus intercalatus which is clearly outlined. From P0 to P4 SP fibers and puncta are established along a 'ladder-like' pattern and from P6 to P15 SP fibers and puncta steadily accumulate in sympathetic nuclei at all spinal levels. By P15 the nuclei intermediolateralis, pars principalis and funicularis, and the nucleus intercalatus are clearly outlined by SP immunoreactivity while the central autonomic region (lamina X) contains heterogeneous bands of SP immunoreactivity. From P20 to P30, SP fibers and puncta accumulate in each autonomic nucleus and longitudinal SP connections form between each adjacent nucleus intermediolateralis pars principalis. Along the spinal midline the nucleus intercalatus pars paraependymalis and the dorsal commissural nucleus emerge from the central autonomic region as separate SP-innervated nuclei. On P40 a period of reorganization takes place so that SP fibers within sympathetic nuclei become more diffuse and the nucleus intercalatus becomes more complex in appearance. The adult SP pattern is formed by P60 when the dorsal commissural nucleus dense core becomes the last autonomic region to be SP innervated. In addition, a transient population of immunohistochemically demonstrable cervical-thoracic laminae VII and X SP cell bodies are observed from P2 to P15.

Aging↗
PubMed1988

Neuropeptide Y immunoreactivity is preferentially located in rat lumbar sexually dimorphic nuclei.

The distribution of neuropeptide Y-like immunoreactivity (NPY-LI) was examined in the ventral gray lumbar spinal cord of male and female rats. Fibers containing NPY-LI were distributed in a sexually dimorphic manner in three motor nuclei: the male cremaster nucleus (CN), spinal nucleus of the bulbocavernosus (SNB) and the dorsolateral nucleus, pars medialis (mDLN) receive a greater number of fibers with NPY-LI than females. Fibers with NPY-LI had the following ratios: males, mDLN greater than or equal to SNB greater than CN greater than dorsolateral nucleus, pars lateralis (1DLN) greater than remaining lumbar ventral gray horn motoneurons (VGH); females, mDLN greater than or equal to SNB greater than or equal to CN greater than VGH greater than or equal to 1DLN. In addition, a previously undescribed small column of motoneurons, located between mDLN and SNB, is outlined by fibers which contain NPY-LI in both sexes. The role of NPY in lumbar sexually dimorphic nuclei is presently unknown.

Animals↗
PubMed1988

Neuropeptides and neuropathology in the amygdala in Alzheimer's disease: relationship between somatostatin, neuropeptide Y and subregional distribution of neuritic plaques.

This study examined the amygdaloid complex in Alzheimer's disease (AD). We compared the distribution and morphology of somatostatin (SOM-) and neuropeptide Y-immunoreactive (NPY-IR) neurons in the amygdala with the distribution of neuritic plaques (NP) and acetylcholinesterase (AChE) staining patterns in various subnuclei. We found that in AD, there was an increase in the number of small, atrophic neurons for both SOM and NPY, and subregional analysis revealed similar size reductions in all subnuclei. In contrast, the highest density of NP was found in the corticomedial nuclei and densest staining for AChE in the basal nucleus. Although NPY- and SOM-IR fibers were occasionally associated with NP, a dense, morphologically preserved peptidergic fiber-network was found in all areas including subnuclei with high numbers of NP. Our study indicates that atrophic SOM- and NPY-IR neurons are not correlated with the subregional distribution of NP or cholinesterase staining pattern of the amygdala, and suggests that alterations in SOM and NPY neurons are not characteristics of the primary pathogenic process that underlie the formation of NP or cholinergic cell loss in AD.

Acetylcholinesterase↗
PubMed1988

Biochemical and morphological effects of castration on the postorganizational development of the hypogastric ganglion.

The biochemical and morphological development of the sympathetic hypogastric ganglion (HG) was examined subsequent to postnatal castration at 10-11 days of age. Previous studies suggested that tyrosine hydroxylase (T-OH) activity, an index of noradrenergic maturation, and choline acetyltransferase (ChAT) activity, a marker for preganglionic terminal formation, were dependent on gonadal hormones during normal ontogeny. In the present studies, morphometric analyses of the HG revealed that the cross-sectional area of the cell soma and nucleus were significantly reduced following postnatal castration at day 10. Conversely, castration produced no change in the number of HG neurons. In addition, postnatal castration prevents the development of postsynaptic T-OH activity to a greater extent than ganglionic protein resulting in a significant loss of T-OH specific activity. In contrast, presynaptic ChAT activity was reduced in parallel with ganglionic protein, thus ChAT specific activity was unchanged. Testosterone replacement therapy, even in groups where treatment was delayed for up to 2 weeks after castration, completely reversed deficits in both T-OH and ChAT activities. These studies suggest that altered development of ganglion protein subsequent to postnatal castration is related to decreases in the size of neurons and not to the loss of neurons. The lack of cell loss also suggest that decreased levels of postsynaptic T-OH activity results from a loss of enzyme activity per cell and the decreased levels of ChAT activity probably represent fewer presynaptic terminals per neuron. In addition, delayed testosterone replacement subsequent to castration was effective in restoring enzyme activities suggesting an 'activational' not 'organizational' role for testosterone after postnatal day 10.

Animals↗
PubMed1988

Thyroid test abnormalities in traumatic brain injury: correlation with neurologic impairment and sympathetic nervous system activation.

Acute illness is well known to affect thyroid function, but there are few studies correlating the severity of the underlying medical problem with indexes of thyroid function and little is known about its cause. Traumatically brain-injured patients were selected because they were a relatively homogeneous, previously healthy group with a condition whose severity was readily quantifiable. In 66 such patients, the relationships between changes in thyroid function tests (thyroxine, free thyroxine, triiodothyronine, reverse triiodothyronine, and thyrotropin levels), catecholamine and cortisol concentrations measured on admission and again four days after the accident, and neurologic function assessed by the Glasgow Coma Score (GCS) were studied. Triiodothyronine and thyroxine levels fell significantly within 24 hours of injury. Four days after the accident, patients with the greatest neurologic dysfunction had the lowest triiodothyronine and thyroxine levels; significant correlations were present between the Day 4 GCS and concomitant thyroxine (r = 0.47, p less than 0.0001), free thyroxine (r = 0.32, p less than 0.02), and triiodothyronine (r = 0.50, p less than 0.0001) levels. Reverse triiodothyronine values remained unchanged throughout the study even in the most severely affected patients; the rise in thyrotropin levels was not significant (1.2 +/- 0.2 to 1.7 +/- 0.3 microU/ml, p = NS). Patients who died or remained vegetative had thyroxine and triiodothyronine levels 30 percent to 50 percent lower than those who had a good recovery (p less than 0.05). Highly significant correlations were present between Day 4 thyroxine and triiodothyronine levels and admission and Day 4 norepinephrine and epinephrine concentrations. There was no association between admission or concomitant cortisol levels and thyroid function on Day 4; treatment with high-dose dexamethasone did not influence these indexes. Thus, patients with traumatic brain injury exhibit a gradient of thyroid dysfunction that occurs promptly, is dependent upon the degree of neurologic impairment, and reflects ultimate outcome. The significant association with catecholamine levels suggests a role for sympathetic nervous system activation in its causation, independent of a generalized stress response, since there is no correlation of thyroid test abnormality with the degree of adrenocortical secretion.

Adult↗
PubMed1988

The morphology and distribution of rat serotoninergic intraspinal neurons: an immunohistochemical study.

An immunohistochemically derived morphological description of a diverse population of rat lamina VII and X intraspinal 5HT neurons is provided. These bipolar or multipolar neurons occur most frequently in lamina X, dorsal or dorsolateral to the central canal, in thoracolumbar, sacral, and coccygeal spinal segments. These 5HT intraspinal neurons are found in normal rat spinal cords as well as in spinal cords that have been hemisected or transected 60 days prior to serotonin immunostaining. Therefore, 5HT intraspinal neurons are the probable source of the biochemically detectable 5HT that remains in the spinal cord distal to a spinal transection. In the rat, serotonin intraspinal neurons are most often associated with spinal autonomic nuclei but it is unknown if they are preganglionic in nature.

Animals↗
PubMed1988

Free and total catecholamines in critical illness.

The magnitude of circulating free and total (free plus conjugated) catecholamine responses to a strong and sustained stimulus was investigated in four groups of patients: traumatic brain injury (n = 24), vascular brain injury (n = 10), polysystem trauma (n = 7) and medical/surgical patients in an intensive care unit (n = 29). Despite significant three- to sevenfold elevations in both free and total norepinephrine (NE) and epinephrine (E), the ratio of free to total NE and E remained constant over a very broad range of values. The proportion of free E was twice normal (30.1-33.5 vs. 16.2%) in all but patients with polytrauma, whereas the percentage of free NE was unchanged in all patients (43.0%). All dopamine (DA) parameters remained generally normal. In the patients with traumatic or vascular brain injury, significant inverse correlations were present between the degree of neurological dysfunction, as indicated by the concomitant Glasgow coma score, and free NE, E, and DA and total NE and DA levels. Thus, during conditions of intense and prolonged catecholamine release, the proportion of free catecholamine remains constant and the total as well as free catecholamine concentration is proportional to the Glasgow coma score.

Critical Care↗