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Biomedical subjects

D Jordan

Publications and source records attributed to D Jordan.

At least 91 records · Page 5Linked to original sources

Esmolol hydrochloride, sodium nitroprusside, and isoflurane differ in their ability to alter peripheral sympathetic responses.

To demonstrate that esmolol, sodium nitroprusside, and isoflurane differ in their abilities to alter adrenal medullary blood flow and other peripheral sympathetic responses to hypotension, 16 mongrel dogs anesthetized with pentobarbital were allocated randomly to one of four test groups and given two hypotensive stimuli, separated by 1 h, to a mean arterial blood pressure of 60 mm Hg for 10 min. The first stimulus, induced by blood loss into a pressurized bottle system, constituted the control for each animal. The second hypotensive stimulus was created by either repeat blood loss (Group 1), esmolol infusion (Group 2), sodium nitroprusside infusion (Group 3), or isoflurane administration (Group 4). Before and 10 min into hypotension, the variables of abdominal organ blood flow, adrenal medullary blood flow, arterial norepinephrine and epinephrine concentrations were measured. In the control animals (Group 1), comparable decreases in abdominal organ blood flow and similar increases in adrenal medullary blood flow, norepinephrine, and epinephrine were elicited by the first and second hypotensive stimulus. Esmolol-induced hypotension (Group 2) abolished the increase in adrenal medullary blood flow and attenuated the increase in epinephrine by 65% (P < 0.03). The decrease in abdominal organ blood flow and the increase in norepinephrine were similar to that observed during baseline hemorrhagic hypotension. In contrast, sodium nitroprusside-induced hypotension (Group 3) abolished abdominal organ vasoconstriction whereas the increases in adrenal medullary blood flow, norepinephrine, and epinephrine were comparable to baseline hemorrhagic hypotension. In fact, abdominal organ blood flow increased 2.5-fold (P < 0.001) during hypotension with SNP. Isoflurane 2%, 1.54 minimum alveolar anesthesia concentration (Group 4), abolished the increases in adrenal medullary blood flow, norepinephrine, and epinephrine observed during baseline hemorrhagic hypotension and attenuated the decrease in abdominal organ blood flow by 70% (P < 0.001). These data demonstrate that esmolol, sodium nitroprusside, and isoflurane differ radically in their ability to alter or blunt peripheral sympathetic responses to hypotension, and suggest that isoflurane is the drug most effective in blunting multiple responses of the peripheral sympathetic system.

Adrenergic beta-Antagonists↗

Isoflurane-induced splanchnic sympathectomy.

To ascertain whether isoflurane produces a peripheral splanchnic sympathectomy as compared to fentanyl or pentobarbital anesthesia, 12 mongrel dogs (30-45 kg) were allocated randomly to one of three anesthetic test groups, tracheally intubated, surgically prepared, and subjected to unilateral electrical stimulation of the greater splanchnic nerve. Anesthetically, Group 1 animals (n = 4) received pentobarbital, Group 2 animals (n = 4) were administered fentanyl, and Group 3 animals (n = 4) received isoflurane. Stimulation continued for 90 min. Each second of stimulation consisted of 20 stimuli of 0.5 minimum alveolar anesthetic concentration duration and 5 V intensity, delivered during a 0.2-s interval, followed by an 0.8-s pause. To assess splanchnic sympathetic responses, mean arterial blood pressure, heart rate, pulmonary artery diastolic, cardiac output, adrenal blood flow, adrenal and arterial norepinephrine (N) and epinephrine (E) were obtained before and at 5, 10, 15, 30, 45, 60, and 90 min during stimulation. In Group 1 animals (pentobarbital), electrical stimulation elicited marked increases in mean arterial blood pressure, pulmonary artery diastolic, and cardiac output (P < 0.001). Examination of the adrenal effluent, which was exteriorized from the animal during the protocol, revealed that adrenal blood flow, adrenal vein N and E concentrations dramatically increased (P < 0.0001). Arterial N and E concentrations remained unchanged. Results of Group 2 animals (fentanyl) were similar to those of Group 1; mean arterial blood pressure, pulmonary artery diastolic, and cardiac output increased (P < 0.005). Adrenal blood flow, adrenal vein N and E increased dramatically (P < 0.0001).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Brain banking for immunocytochemistry and autoradiography.

The aim of a human brain bank is to establish groups of matched brains (normal control versus pathological groups) for studying human diseases of the nervous system. This bank is obtained by means of autopsy performed with a very short post-mortem delay and from clinically and neuropathologically well-documented patients. According to research protocols, two types of brain tissue storage are performed: fixed tissue or frozen tissue. Brain dissection procedures are performed according to precise anatomical boundaries of each brain region. This paper will center on the questions raised by brain banking in relation to histological and immunocytochemical studies and to biochemistry and autoradiography of binding sites. The lack of neuroanatomical data of the human brain leads us to compare anatomical results obtained in animals to that of the human. Moreover, it is clear that human brains present numerous interindividual differences (Kopp et al., 1977; Jack et al., 1989). Therefore, investigations of the human brain should be made on a large series of brains indicating the necessity of a well-documented brain bank of tissue from normal controls and patients.

Autoradiography↗

Disappearance of hypothalamic TRH asymmetry in suicide patients.

The aim of the present study was to investigate the functional and/or pathological significance of the hemispherical lateralization of TRH using radioimmunoassay to determine the TRH concentration of nuclei and areas within the hypothalamus of suicide patients, with matching measurement being carried out on control subjects. In suicide patients, we found no significant difference in TRH concentration between the left and right intrahypothalamic structures, while the group used as control subjects (see Borson-Chazot, 1986) showed a significant left side predominance in the ventromedial nucleus, paraventricular nucleus and area dorsalis. As regards the TRH concentration in the right intrahypothalamic structures, no significant difference was found between the suicide patients and the control subjects. The absence of the left TRH predominance for the three intra-hypothalamic structures in question may be of pathological significance.

Adult↗

Quantitative autoradiographic study of somatostatin and neurotensin binding sites in medulla oblongata of SIDS.

Quantitative autoradiography analysis of neurotensin (NT) and somatostatin (SS) binding sites was performed on coronal sections of the medulla oblongata from 2 fetuses, 6 controls and 7 victims of Sudden Infant Death Syndrome (SIDS). Throughout the first postnatal year, mean SS binding site density was similar in controls and SIDS in all structures of the medulla oblongata. The density of neurotensin binding sites was significantly higher in the nucleus of tractus solitarius (NTS) of SIDS than in controls, but there was no significant differences in the other areas of the medulla oblongata. Our findings suggest an immature developmental pattern of increased NT binding sites the NTS of SIDS. This alteration may be related to an abnormal central cardiorespiratory and arousal control which is thought to be present in SIDS.

Autoradiography↗

Ontogeny of peptides in human hypothalamus in relation to sudden infant death syndrome (SIDS).

The brains of mammals are not mature at birth, in particular in humans. Growth and brain development are influenced by the hormonal state in which the hypothalamus plays the major regulatory role. The maturation of the hormonal patterns leads to the physiological establishment of chronological variations as revealed by the circadian variations of both hypothalamic peptides and pituitary hormones (as illustrated for hypothalamic-pituitary-thyroid axis by the determination of thyro-stimulating hormone (TSH) and thyrotropin-releasing hormone (TRH) circadian rhythms in the rat (Jordan et al., 1989)). It has been established that hypothalamic peptide variations are regulated by hormonal feed-back and amine systems, with the maturation of the latter also being dependent upon the whole functional maturation of the brain. Though these systems have been studied in the rat, very little information is currently available with regard to the human brain. The only biochemical or immunohistochemical information published to date concerns either the fetus or the adult. We have studied four main peptidergic systems (somatostatin-releasing inhibiting factor (SRIF), thyrotropin-releasing hormone (TRH), luteinizing hormone-releasing hormone (LHRH) and delta sleep inducing peptide (DSIP) in post-mortem adults and infants and in sudden infant death syndrome (SIDS) brains either by autoradiography and/or immunochemistry of radioimmunology. From a technical point of view, human brain studies display certain pitfalls not present in animal studies. These may be divided into two subclasses: ante- and post-mortem. Ante-mortem problems concern mainly sex, laterality, nutritional and treatment patterns while post-mortem problems concern post-mortem delay and conditions before autopsy and hypothalamic dissection. This might induce dramatic changes in morphological, immunochemical and autoradiographic evaluations. The matching of pathological subjects with controls is particularly difficult in the case of SIDS because of the rapid changes which take place in physiological regulatory processes during the first year of life. Thus, the treatment of hypothalamic tissue samples both for immunochemistry, radioimmunology and autoradiographic studies required techniques which must be rigorously controlled. For example, SRIF studies were carried out with three different antibodies, which gave similar results. The use of different technical procedures as well as different antibodies is discussed. These types of differences might explain, at least in part, the discrepancy observed until now. As previously described in the fetus (Bugnon et al., 1977b; Bouras et al., 1987), we confirmed that in the infant hypothalamic SRIF immunoreactive cell bodies are present in the paraventricular and suprachiasmatic nuclei and in the periventricular area.(ABSTRACT TRUNCATED AT 400 WORDS)

Adult↗

Scripps Clinic: in transition to the on-line medical record.

The TMI system was implemented at our main campus on March 4, 1991, and at this point we are very pleased with all aspects of system performance. Since the conversion, the number of jobs dictated by our physicians has increased 20%, and we interpret this increase as an objective measure of physician satisfaction with the system. An increasing number of physicians are accessing lab results and documents from home via modem to review the next day's patients or while on-call. Transcription productivity has improved and enthusiasm for the system is high. Requests for chart documentation from our business office have decreased 60% due to the ability to access and print documents directly from the mainframe. The next phase in our information plan involves the installation of the TMI system at our regional clinics and our inpatient transcription unit. Further steps in the transition to on-line medical records, such as the conversion of 600,000 active and archived records, awaits the further development of technology in order to be feasible and cost effective. Our experience has shown that developing complex applications such as the TMI demands perseverance and a willingness to work closely with multiple vendors and products in order to identify the best options in a rapidly developing field. Extensive involvement of end users early in the planning process helped us to secure and implement a system with a high level of user acceptance and satisfaction.

Ambulatory Care Information Systems↗

[Abnormalities of the nervous system in sudden infant death syndrome].

Anomalies seem to be present in the brain of infants who died of sudden infant death syndrome. They imply dendritic synapses, myelinisation, some neurotransmitters, some peptides, their enzymes and receptors. More precisely, catecholaminergic systems seem to be abnormal. The changes were found mainly in brain stem, in vegetative central areas. These anomalies are probably maturational in nature. They could represent a fragility of vegetative control systems, especially cardiorespiratory and swallowing control systems. They probably do not explain, per se, the occurrence of death; they probably would need to be potentiated by additional etiological factors (environmental, viral, etc). These anomalies have to be considered as provisional and, in our opinion, need confirmation. Apart from the brain stem, other areas are under investigation, particularly cerebral structures implied in temperature control, sleep-wakefulness control and hemispheric structures.

Brain↗

Regional distribution of somatostatin binding sites in the human hypothalamus: a quantitative autoradiographic study.

Using in vitro quantitative autoradiography and [125I]Tyr0-D-Trp8SRIF 14 as radioligand, we characterized the detailed distribution of somatostatin binding sites in human hypothalamus of both infants and adults. Guanosine triphosphate pretreatment, before incubation, allowed us to detect higher [125I]Tyr0-D-Trp8SRIF 14 binding site densities in hypothalamic structures such as preoptic and anterior hypothalamic areas and ventromedial and dorsomedial nuclei. In contrast, guanosine triphosphate was without effect in the other hypothalamic regions. The regional effects of guanosine triphosphate pretreatment were not different in infant and adult hypothalamus. Scatchard analysis showed that in a guanosine triphosphate-sensitive region (preoptic area) and a guanosine triphosphate-insensitive area (infundibular nucleus), [125I]Tyr0-D-Trp8SRIF 14 bound to a single class of binding sites. Affinities were similar in both regions, not modified by guanosine triphosphate pretreatment and not different in the adult (1.5 +/- 1.2 nM vs 3.2 +/- 2.1 nM for preoptic area and infundibular nucleus, respectively) and infant (0.9 +/- 0.5 nM vs 2.4 +/- 1.7 nM for preoptic area and infundibular nucleus). [125I]Tyr0-D-Trp8SRIF 14 binding sites were widely distributed in the anterior, mediobasal and posterior hypothalamus. Somatostatin 28 was twice as potent as somatostatin 14 to displace [125I]Tyr0-D-Trp8SRIF 14 binding in the preoptic area and infundibular nucleus. However, IC50s were 30 times lower in the preoptic area as compared with the infundibular nucleus. In adult as well as in infant, high densities were found mainly in the diagonal band of Broca, preoptic area and infundibular nucleus. Intermediate densities were localized in the anterior hypothalamic area, ventromedial, dorsomedial and lateral mammillary nuclei. The dorsal hypothalamic area, the paraventricular and medial mammillary nuclei displayed low but measurable densities. The only marked difference in the distribution of [125I]Tyr0-D-Trp8SRIF 14 binding sites in adult vs infant was observed in the medial and tuberal nuclei where the concentrations were seven-fold higher in adult hypothalamus.

Adult↗

Investigation of the effects of IVth ventricular administration of the 5-HT2 agonist, 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI), on autonomic outflow in the anaesthetized cat.

1. The effects of IVth ventricular injections of 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI) on renal, splanchnic and cardiac sympathetic nerve activities, phrenic nerve activity, arterial blood pressure, heart rate, femoral arterial conductance, tracheal and intragastric pressures were investigated in alpha-chloralose anaesthetized, neuromuscular blocked and artificially ventilated cats. 2. Cumulative doses of DOI (80, 160 and 320 nmol kg-1) injected into the IVth ventricle caused an increase in mean arterial blood pressure, a fall in femoral arterial conductance, an increase in tracheal pressure and a decrease in the rate of phrenic nerve bursts but did not affect any of the other variables recorded. 3. Even after i.v. administration of the peripheral 5-HT2 antagonist BW501C67 (2 mg kg-1) following the highest dose of DOI there was still a significant pressor response, a fall in femoral arterial conductance and small increase in tracheal pressure. 4. In control experiments, intravenous infusion of noradrenaline to raise blood pressure to the levels obtained during the cumulative doses of DOI caused large falls in renal, splanchnic and cardiac nerve activities which were all significantly lower than those recorded during the cumulative doses of DOI. 5. The results of this study provide evidence for a brainstem site of action of DOI in producing hypertension and further support the hypothesis that central 5-HT2 receptors are involved in the control of skeletal muscle and skin vascular beds.

Amidines↗

Microinjections of 5-HT1A agonists into the dorsal motor vagal nucleus produce a bradycardia in the atenolol-pretreated anaesthetized rat.

1. The effects of microinjections (100 nl) into the dorsal motor vagal nucleus of the 5-HT1A receptor agonists 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) and flesinoxan, the 5-HT2 receptor agonist (+-)-1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane hydrochloride (DOI), the 5-HT3 receptor agonist phenylbiguanide (PBG), the alpha 2-adrenoceptor agonist clonidine and the excitatory amino acid glutamate on heart rate, blood pressure, tracheal pressure and phrenic nerve activity were investigated in atenolol-pretreated rats anaesthetized with sodium pentobarbitone. 2. Microinjections of glutamate (2.5 nmol) caused decreases in blood pressure, heart rate and phrenic nerve activity. In contrast, microinjections of 5-HT (1.2 nmol), 8-OH-DPAT (1.2 nmol) and flesinoxan (1.3 nmol) all caused a bradycardia but had no effect on blood pressure. In addition, 8-OH-DPAT and flesinoxan caused an increase in phrenic nerve activity. 3. Microinjections of DOI, PBG and clonidine had no significant effect on any of the variables recorded. None of the drugs used had any significant effect on tracheal pressure. 4. These results support the hypothesis that activation of 5-HT1A receptors causes excitation of cardiac vagal motoneurones and suggest that these receptors are also important in the control of central respiratory drive.

Animals↗

Mood alterations with a single bout of physical activity.

Although numerous studies have examined the relationship among affect, personality, and physical activity, results are equivocal. Critics have cited inadequate experimental designs and analyses as the bases for ambiguity. This study addressed two identified weaknesses, length of exercise regimen and improper selection of subjects. Subjects were 72 college-age students who participated in one of three 75-min. activity classes (running, karate, weight lifting) and a lecture class (control subjects). The Profile of Mood States Test was administered prior to and immediately after exercise bouts. Analyses of variance and multiple t tests indicated that participating in a single bout of exercise significantly reduced reported total mood disturbance, tension, depression, anger, and confusion.

Adult↗

The autonomic nervous system and behaviour.

This short paper reviews what is known about the autonomic responses that accompany stressful type behaviour and provides a description of the neural mechanisms which integrate the autonomic and somatic motor activities during such behaviour. First, I briefly summarise what is known about the mechanisms which normally regulate autonomic outflow. Then, I compare the neural sites responsible for eliciting behavioral responses. Next, I show how these behavioural and autonomic responses are evoked in parallel during stressful behaviour. Finally, I describe one example of how normal homeostatic mechanisms are overridden during the stressful behaviour pattern. Many of these topics have recently been reviewed in detail. Since much of the experimental work has been done on experimental animals, either anaesthetized or awake, it is important to keep in mind that their responses may not always be the same as those evoked in humans, so I also refer to what we know in human subjects.

Animals↗

Actions of 8-OH-DPAT on sympathetic and respiratory drives, blood pressure and heart rate in the rabbit.

The effects of i.v. 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) on renal and cardiac sympathetic nerve activity, phrenic nerve activity, blood pressure and heart rate were investigated in urethane and pentobarbitone anaesthetised rabbits. Cumulative doses of 8-OH-DPAT (0.5-512 micrograms kg-1) in urethane anaesthetised rabbits, in which simultaneous recordings of renal and phrenic nerve activity were made, caused dose related decreases in mean blood pressure which were maximal after 32 micrograms kg-1 and dose related decreases in heart rate. Effects on renal and phrenic nerve activity were variable. A single dose of 8-OH-DPAT (32 micrograms kg-1) in either urethane or pentobarbitone anaesthetised rabbits, in which simultaneous recordings of cardiac as well as renal and phrenic nerve activity were made, caused significant falls in blood pressure, heart rate and cardiac nerve activity. Renal nerve activity showed no significant change whilst phrenic nerve activity tended to increase but this was only significant in the pentobarbitone anaesthetised rabbits. In all experiments the bradycardia produced by 8-OH-DPAT was unaltered by atropine. These results show that in the anaesthetised rabbit the hypotension and bradycardia caused by 8-OH-DPAT were associated with a decrease in cardiac nerve activity, increased central respiratory drive, and no change in renal nerve activity or vagal tone.

8-Hydroxy-2-(di-n-propylamino)tetralin↗

Anatomical distribution of LHRH-immunoreactive neurons in the human infant hypothalamus and extrahypothalamic regions.

The morphological features and distribution of luteinizing hormone-releasing hormone (LHRH)-immunoreactive cell bodies and fibers of the hypothalamic and the neighboring mesencephalic regions were studied in the normal newborn infant by immunohistochemistry. Within the hypothalamus, numerous LHRH-immunoreactive like (IL) cell bodies were found mainly in the ventral portion of the infundibular nucleus close to the median eminence and at a lower extent in the medial preoptic area. In addition, sparse immunoreactive cell bodies were displayed in the paraventricular and medial mammillary nuclei. The mesencephalon also exhibited rare immunoreactive cell bodies in the periaqueductal gray. LHRH-IL fibers, predominantly varicose, formed a continuum from the septo-preoptico level to the mesencephalon. In the hypothalamus, the median eminence exhibited the highest LHRH innervation. LHRH-IL fibers are also observed in the lamina terminalis, the medial preoptic area, the suprachiasmatic, the supraoptic, the peri- and the paraventricular nuclei. In the last two nuclei, some fibers projected to the dorsomedial and ventromedial nuclei whereas others were in close relation with the ependyma. The mesencephalon displayed low LHRH-IL fibers, present essentially in the raphe and interpeduncular nuclei and around the ependyma. When compared with data obtained in other mammals, the present findings agree well with the general distribution and morphological features of LHRH-IL neuronal structures reported elsewhere.

Brain↗

Computerized tomography in the evaluation of myasthenia gravis.

Thymomas occur in 10% to 15% of patients with myasthenia gravis. Since not all patients are referred for thymectomy, a test that could reliably predict the presence or absence of a thymoma would be of great assistance in the management of these patients. We studied all patients referred for thymectomy at Walter Reed Army Medical Center from 1983 to 1989. Complete records were available for 13 patients. Computerized tomography (CT) correctly predicted the presence of a thymoma in one patient and falsely predicted a thymoma in a patient with a thymic cyst; it accurately predicted the absence of a thymoma in the remaining 11 patients. The sensitivity of CT scanning was 100%, the specificity was 92%, and the accuracy was 92%, results that are in agreement with previously published data. Compared to conventional chest roentgenography, CT scanning provided a more precise anatomic localization, and accurately predicted local invasion. We recommend a CT scan of the mediastinum in all patients with myasthenia gravis to avoid delayed diagnosis of thymoma in patients who normally would not be referred for thymectomy.

Adult↗

[Does the duration of work disability in patients with uncomplicated duodenal ulcer affect risk of recurrence the following year? A multicenter study].

At present there is no therapeutic approach conducive to success, with the help of which the inclination to recidivation of duodenal ulcer might be restricted. In a prospective multicentric study with the help of two randomized groups of patients (group A: 13 days of disablement, group B: 37 days of disablement) was tried to prove a possible influence of the duration of the disablement on the inclination to recidivation in ulceration. In comparable groups of patients out of 99 evaluable documentations of patients in group A were found 62.5% of recidivations, in group B 68.6%. The difference was not significant. No connection could be found between duration of the disablement in ulceration and inclination to recidivation. Smokers have a distinctly higher inclination to recidivation than non-smokers.

Absenteeism↗