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Biomedical subjects

M J Chandler

Publications and source records attributed to M J Chandler.

At least 19 recordsLinked to original sources
PubMed1992

Intracardiac phenylbiguanide causes excitation of spinal neurons by activation of cardiac sympathetic afferents.

The responses of spinothalamic, spinoreticular, and unidentified spinal neurons to intracardiac administration of phenylbiguanide, a 5-HT3 receptor agonist, were examined in anesthetized cats and monkeys. Eighteen neurons were excited, 5 were inhibited, and 12 were unresponsive to this stimulus. Results suggest that cardiac sympathetic afferents mediate the excitatory responses produced by phenylbiguanide, because bilateral cervical vagotomy failed to block these responses, and aortic injections of phenylbiguanide had little effect on cell activity.

Adrenergic Fibers↗
PubMed1992

Responses of neurons in ventroposterolateral nucleus of primate thalamus to urinary bladder distension.

The purpose of this study was to examine effects of a noxious visceral stimulus, urinary bladder distension (UBD), on cells in the ventroposterolateral (VPL) nucleus of anesthetized monkeys. We hypothesized that processing of visceral information in the VPL nucleus of the thalamus is similar to spinothalamic tract (STT) organization of visceral afferent input. Urinary bladder distension excites sacral and upper-lumbar STT cells that have somatic input from proximal somatic fields; whereas, thoracic STT cells are inhibited by UBD. Extracellular action potentials of 67 neurons were recorded in VPL nucleus. Urinary bladder distension excited 22 cells, inhibited 9 cells, and did not affect activity of 36 cells. Seventeen of 22 cells excited by UBD also received convergent somatic input from noxious squeeze of the hip, groin, or perineal regions. No cells activated only by innocuous somatic stimuli were excited by UBD. Five of 9 cells inhibited by UBD had upper-body somatic fields. There was a significant tendency for VPL neurons excited by UBD to have proximal lower-body somatic fields that were excited by noxious stimulation of skin and underlying muscle (P less than 0.001). Antidromic activation of 4 thalamic neurons affected by UBD showed that visceral input stimulated by UBD reached the primary somatosensory (SI) cortex.

Action Potentials↗
PubMed1992

Evidence that C1 and C2 propriospinal neurons mediate the inhibitory effects of viscerosomatic spinal afferent input on primate spinothalamic tract neurons.

1. Lumbosacral spinothalamic tract (STT) neurons can be inhibited by noxious pinch of the contralateral hindlimb or either forelimb and by electrical stimulation of cardiopulmonary sympathetic, splanchnic, and hypogastric afferents. A previous study found that spinal transections between C2 and C4 sometimes abolished the inhibitory effect of spinal afferent input and sometimes left it intact. This suggested that propriospinal neurons in the C1 and C2 segments might mediate this effect. To test whether neurons in the C1 and C2 segments were involved in producing this inhibitory effect, the magnitude of the reduction in neural activity was measured in the same STT neuron before and after spinal transection at C1 or between C3 and C7. 2. All neurons were antidromically activated from the contralateral thalamus and thoracic spinal cord. For us to accept a neuron for analysis, the characteristics of the somatic input and the latency and shape of the antidromatic spike produced by spinal cord stimulation had to be the same before and after the spinal transection. Also, spinal transection often causes a marked increase in spontaneous cell activity, which may affect the magnitude of an inhibitory response. To avoid this confounding problem, a cell was accepted for analysis only if it showed marked inhibition of high cell activity evoked by somatic pinch before spinal transection. For analysis 13 STT neurons met these criteria: 6 neurons were in monkeys with C1 transections, and 7 neurons were in animals with transections between C3 and C7.(ABSTRACT TRUNCATED AT 250 WORDS)

Afferent Pathways↗
PubMed1992

Segmental organization of visceral and somatic input onto C3-T6 spinothalamic tract cells of the monkey.

1. Referred pain of visceral origin has three major characteristics: visceral pain is referred to somatic areas that are innervated from the same spinal segments as the diseased organ; visceral pain is referred to proximal body regions and not to distal body areas; and visceral pain is felt as deep pain and not as cutaneous pain. The neurophysiological basis for these phenomena is poorly understood. The purpose of this study was to examine the organization of viscerosomatic response characteristics of spinothalamic tract (STT) neurons in the rostral spinal cord. Interactions were determined among the following: 1) segmental location, 2) effects of input by cardiopulmonary sympathetic, greater splanchnic, lumbar sympathetic, and urinary bladder afferent fibers, 3) location of excitatory somatic field, e.g., hand, forearm, proximal arm, or chest, 4) magnitude of response to hair, skin, and deep mechanoreceptor afferent input, and 5) regional specificity of thalamic projection sites. 2. A total of 89 STT neurons in segments C3-T6 were characterized for responses to visceral and somatic stimuli. Neurons were activated antidromically from the contralateral ventroposterolateral oralis or caudalis nuclei of the thalamus. Cell responses to visceral and somatic stimuli were not different on the basis of the thalamic site of antidromic activation. Recording sites for 61 neurons were located histologically; 87% of lesion sites were located in laminae IV-VII or X. There was no relationship between response properties of the neurons and spinal laminar location. 3. Different responses to visceral stimuli were observed in three zones of the rostral spinal cord: C3-C6, C7-C8, and T1-T6. In C3-C6, urinary bladder distension (UBD) and electrical stimulation of greater splanchnic and lumbar sympathetic afferent fibers inhibited STT cells. Electrical stimulation of cardiopulmonary sympathetic afferents increased cell activity in C5 and C6 and either excited or inhibited STT cells in C3 and C4. In the cervical enlargement (C7-C8), STT cells generally were either inhibited or showed little response to stimulation of visceral afferent fibers. In T1-T6, input from greater splanchnic and cardiopulmonary sympathetic afferent nerves increased activity of STT cells. Lumbar sympathetic afferent input inhibited cells in T1-T2 and had little effect on cells in T3-T6, whereas UBD decreased cell activity in all segments studied. 4. In general, stimulation of somatic structures increased activity of STT neurons in segments that received primary afferent innervation from the excitatory somatic receptive field or in the segments immediately adjacent to these segments. Only input from the forelimb, especially the hand, markedly excited cells in C7 and C8.+

Afferent Pathways↗
PubMed1991

Inhibitory effects of phrenic afferent fibers on primate lumbosacral spinothalamic tract neurons.

Studies were conducted to determine if electrical or mechanical stimulation of phrenic afferent fibers (PHR) would inhibit the activity of lumbosacral spinothalamic tract (STT) neurons. Twelve monkeys were anesthetized, paralyzed, and artificially ventilated. Extracellular action potentials were recorded from 78 STT neurons located in L2-S3 spinal segments. Electrical stimulation of PHR reduced the activity of 65%, did not affect 33%, and excited 1% of STT neurons. Mechanical stimulation of the diaphragm reduced the activity of 63%, did not effect 34%, and excited 1% of lumbosacral STT neurons. Distention of the urinary bladder (UBD) inhibited 52%, did not affect 23%, excited 23%, and elicited a biphasic response in 1% of STT neurons. However, there was no correlation between the effect of PHR and UBD or somatic classification of the neurons. We conclude that electrical or mechanical stimulation of PHR can produce a generalized inhibition of lumbosacral STT neurons. This inhibitory effect of PHR is similar to inhibitory effects reported for a variety of other afferent systems.

Action Potentials↗
PubMed1991

Projection of nodose ganglion cells to the upper cervical spinal cord in the rat.

Afferent fibers mediating pain from myocardial ischemia classically are believed to travel in sympathetic nerves to enter the thoracic spinal cord. After sympathectomies, angina pectoris still may radiate to the neck and inferior jaw. Sensory fibers from those regions are thought to enter the central nervous system through upper spinal cord segments. We postulated that axons from nodose ganglion cells might project to cervical cord segments. The purpose of this study was to determine the density and pathway of vagal afferent innervation to the upper cervical spinal cord. Following an injection of wheat germ agglutinin conjugated to horseradish peroxidase (WGA-HRP) into the upper cervical spinal cord, approximately 5.8% of cells in the nodose ganglion contained reaction product. Cervical vagotomy did not diminish the density of WGA-HRP labeled cells in the nodose ganglion. However, a spinal cord hemisection cranial to the injection site eliminated labeling of nodose cells. These data indicate that a portion of vagal afferent neurons project from the nodose ganglion to the upper cervical spinal cord. In addition, vagal afferent fibers reach the spinal cord via a central route rather than through dorsal root ganglia.

Animals↗
PubMed1991

Convergence of phrenic and cardiopulmonary spinal afferent information on cervical and thoracic spinothalamic tract neurons in the monkey: implications for referred pain from the diaphragm and heart.

1. Spinothalamic tract (STT) neurons in the C3-T6 spinal segments were studied for their responses to stimulation of phrenic and cardiopulmonary spinal afferent fibers. A total of 142 STT neurons were studied in 44 anesthetized, paralyzed monkeys (Macaca fascicularis). All neurons were antidromically activated from the ventroposterolateral nucleus and/or medial thalamus. 2. Electrical stimulation of phrenic afferent fibers (PHR) excited 43/58 (74%), inhibited 2/58 (3%), and did not affect 13/58 (13%) of cervical STT neurons. Neurons with excitatory somatic fields confined to the proximal limb or encompassing the whole limb were excited to a significantly greater extent by electrical stimulation of PHR than were neurons with somatic fields confined to the distal limb. Mechanical stimulation of PHR by probing the exposed diaphragm excited 11/22 (50%), inhibited 3/22 (14%), and did not affect 8/22 (36%) cervical STT neurons. 3. The technique of minimum afferent conduction velocity (MACV) was used to obtain information about the identity of the PHR that excited 35 cervical STT neurons. Evidence was obtained for excitation of these neurons by group II and III PHR. The mean +/- SE MACV for all neurons was 14 +/- 2 m/s. 4. Electrical stimulation of cardiopulmonary spinal afferent fibers excited 41/57 (72%), inhibited 8/57 (14%), and did not affect 8/57 (14%) of cervical STT neurons. Neurons with excitatory somatic fields confined to the proximal limb or encompassing the whole limb were excited to a significantly greater extent by electrical stimulation of cardiopulmonary spinal afferents than were neurons with somatic fields confined to the distal limb. 5. Excitatory convergence of PHR and cardiopulmonary spinal afferent input was observed for 36/57 (63%) cervical STT neurons. 6. Electrical stimulation of PHR excited 36/84 (43%), inhibited 25/84 (30%), and did not affect 23/84 (27%) of thoracic STT neurons. All of these neurons received excitatory cardiopulmonary spinal afferent input. 7. Neurons were more likely to be excited by electrical stimulation of PHR if they were located in C3-C6 spinal segments. Furthermore, the net excitatory effect of PHR input decreased in more caudal segments, such that thoracic STT neurons were weakly excited relative to cervical STT neurons. 8. We conclude that cervical STT neurons with excitatory somatic fields that include or are restricted to proximal sites are excited by electrical or mechanical stimulation of PHR. Those effects demonstrate a physiological substrate for pain referred from the diaphragm to the shoulder in patients with pleural effusions or subphrenic abscesses.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1990

Urinary bladder and hindlimb stimuli inhibit T1-T6 spinal and spinoreticular cells.

Upper thoracic spinal neurons are primarily excited by cardiopulmonary spinal afferent input but are excited and inhibited by splanchnic afferent input. These data suggest that the greater the number of segments between a spinal neuron and spinal afferent input the greater the probability that the afferent input will inhibit the spinal neuron. Based on this idea we hypothesized that visceral (urinary bladder) and somatic (hindlimb) afferent input would inhibit upper thoracic spinal neurons. To test this hypothesis the activities of 69 spinal and 27 spinoreticular tract neurons in 45 alpha-chloralose-anesthetized cats were studied. Only neurons excited by both visceral and somatic thoracic afferent input were studied. Urinary bladder distension (UBD) inhibited 48 (50%), excited 6 (6%), and did not affect 41 (43%) of these neurons. Also, UBD inhibited the excitatory responses of these cells to noxious visceral and somatic stimuli. Hindlimb pinch also inhibited greater than 50% of the neurons. These data indicate that visceral and somatic afferent input to the lumbosacral spinal cord inhibits the activity of upper thoracic neurons. This inhibitory effect may play a role in localization of sensory and motor responses to noxious stimuli.

Afferent Pathways↗
PubMed1989

Effects of chemical and electrical stimulation of the midbrain on feline T2-T6 spinoreticular and spinal cell activity evoked by cardiopulmonary afferent input.

Responses to electrical and chemical stimulation of the periaqueductal gray (PAG) and midbrain reticular formation (RF) were examined on extracellular activity of 28 spinoreticular tract (SRT) and 56 spinal neurons in T2-T6 segments of anesthetized cats. All cells received excitatory viscerosomatic convergent input from the left forelimb triceps region and from cardiopulmonary sympathetic afferents. Evoked activity that resulted from pinching the left triceps was reduced by PAG and midbrain RF stimulation (100 Hz, 100 microseconds, 50-500 microA). Visceral afferent input to the neurons was elicited during electrical stimulation of cardiopulmonary sympathetic afferent fibers and following injection of bradykinin into the left atrium of the heart. Electrical stimulation of the PAG and adjacent RF decreased A-delta and C-fiber activation of these neurons produced during electrical stimulation of cardiopulmonary afferents and decreased the activity of cells during excitatory responses to intracardiac bradykinin. Electrical stimulation of the PAG or midbrain RF similarly decreased spontaneous and evoked cell activity. Selective activation of cell bodies with microinjection of glutamate into the PAG reduced the activity of 6 of 8 cells whereas glutamate injections into midbrain RF reduced the activity of only 3 of 13 neurons. This difference in the effectiveness of chemically stimulating the PAG vs midbrain RF was significant (P less than 0.05). These data demonstrate that (1) neuronal activity evoked by visceral afferent input from the heart was decreased by electrical stimulation of the PAG and midbrain RF and (2) a portion of this descending inhibition may be mediated by cell bodies in the PAG.

Action Potentials↗
PubMed1989

Effects of intracardiac bradykinin and capsaicin on spinal and spinoreticular neurons.

The responses of thoracic spinal and spinoreticular tract (SRT) neurons to activation of cardiac spinal afferents by injections of bradykinin (BK) and capsaicin (CAP) into the left atrium or pericardial sac were determined in vagotomized cats anesthetized with alpha-chloralose. Activities of spinal and SRT neurons in the T1-T5 spinal cord were recorded extracellularly. All neurons received excitatory somatic and cardiopulmonary sympathetic afferent input. Application of BK and CAP to the heart excited most SRT neurons and many spinal neurons but also inhibited some spinal neurons. The two drugs often affected spinal but not SRT neurons differently. Capsaicin excited high threshold and high threshold inhibitory neurons but not wide-dynamic range spinal neurons. In contrast, BK excited all three categories of spinal and SRT neurons. The differential responses of spinal neurons to intracardiac BK and CAP suggested that these compounds can stimulate functionally different populations of cardiac sympathetic afferents.

Animals↗
PubMed1989

Cardiac and abdominal vagal afferent inhibition of primate T9-S1 spinothalamic cells.

Effects of electrically stimulating vagal afferents were determined on lumbosacral spinothalamic tract (STT) neurons in the T9-S1 segments. Stimulating left or right vagal afferents inhibited 20 (50%) and excited 4 (10%) of 40 STT neurons. Vagal stimulation reduced activity of the 20 inhibited cells by 71 +/- 6% and reduced the average activity of all 40 STT neurons by 28% from 11.5 +/- 1.3 to 8.3 +/- 1.4 impulses/s (P less than 0.01). Effects of activating thoracic and abdominal or just abdominal vagal afferents were also determined. Stimulating right abdominal vagal afferents inhibited 4 (11%), excited 1 (3%), and did not affect 30 (86%) of the STT neurons and overall did not significantly affect STT cell activity. In contrast, in 33 of these cells stimulation of afferents in the right cervical vagus inhibited 16 (48%), excited 2 (6%), and did not affect 15 (45%) neurons and overall significantly reduced cell activity by 29% (P less than 0.01). These data and those of Ammons et al. (J. Neurophysiol. 50: 926-940, 1983; Circ Res. 53: 603-612, 1983; J. Neurophysiol. 54: 73-89, 1985) suggest that cardiopulmonary but not abdominal vagal afferent input reduces STT cell activity in many spinal segments. This inhibitory vagal reflex may play a role in protecting the heart.

Abdomen↗
PubMed1987

Levels and specificity of antibody in bronchoalveolar lavage (BAL) and serum in an animal model of trimellitic anhydride-induced lung injury.

A study was undertaken to characterize the antibody response in rats exposed to trimellitic anhydride (TMA) by inhalation. Total antibody levels directed to trimellitic rat serum albumin (TM-RSA) from TMA-exposed rats were assayed by an ammonium sulfate technique. Total antibody levels in bronchoalveolar lavage (BAL) and the matched serum were compared by correction for the albumin content of each. An ELISA was developed to detect IgG, IgA, and IgM directed toward TM-RSA in BAL and serum and to compare class-specific antibody levels in BAL and serum by normalizing for albumin content. The specificity of the rat IgG response was determined by ELISA inhibition with TM-RSA and TM-human serum albumin (TM-HSA) and compared with reciprocal inhibition studies with serum from TMA-exposed workers. The levels of total antibody in BAL were three to 15 times greater than the levels found in the matched serum pair. IgG, IgA, and IgM antibodies were detected in the BAL and the serum of TMA-exposed rats but not in control rats. In each of the four rats tested, all antibody classes were present in equal or greater amounts in the BAL than in the serum. Complete inhibition of the rat IgG binding in ELISA was observed when TM-RSA or TM-HSA were added as inhibitors. Human IgG was inhibited in ELISA only by TM-HSA. In an animal model of human lung disease, the levels of total antibody as well as class-specific antibodies directed against TM-RSA were greater in BAL than in serum.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1987

Provocative challenge with local anesthetics in patients with a prior history of reaction.

Possible allergic sensitivity to local anesthetic agents remains problematic for some patients who could benefit from their use. We retrospectively reviewed all our consultations for evaluation of local anesthetic allergy from 1965 to 1985 to assess the safety and efficacy of skin testing and provocative test dosing with a variety of local anesthetic agents. Fifty-nine patients reported 70 reactions from the administration of six different local anesthetics. Fifty-four patients could name one or more local anesthetic agents they believed were responsible, and five patients named only "caine" drugs. Multiple reactions of the same type to the same agent were considered as one reaction. On the basis of their history of reaction, the patients were categorized as follows: anaphylactoid reactions (urticaria, angioedema, wheezing, or hypotension within 1 to 2 hours of exposure), possible anaphylactoid reactions (tachycardia, dizziness, syncope, breathlessness, or pruritus occurring within 1 to 2 hours of exposure), contact dermatitis (a typical eczematous skin eruption after appropriate cutaneous sensitization), and other reactions (nonanaphylactoid reactions other than those already described or those occurring more than 2 hours after exposure). Fifty-nine patients were administered local anesthetics after skin testing and provocative test dosing, including two patients who required intravenous lidocaine (Xylocaine; Astra Pharmaceutical Products, Inc., Westboro, Mass.) acutely to control cardiac arrhythmias. These two patients had reported anaphylactoid reactions to oral antiarrhythmic drugs of the local anesthetic class. Despite the history of previous reactions, there were no positive skin tests or positive provocative drug challenges in any patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Anaphylaxis↗
PubMed1987

A model of immunologic lung injury induced by trimellitic anhydride inhalation: antibody response.

We studied lung injury induced in Sprague-Dawley rats by trimellitic anhydride (TMA) inhalation. Groups of 40 male and 20 female rats were exposed to TMA by inhalation at target concentrations of 0, 10, 30, 100, and 300 micrograms/m3, 6 hours per day, 5 days per week, for 2 weeks. Rats in each exposure group were sacrificed after 10 exposures or rested for 12 days and either sacrificed or received a 6-hour TMA challenge at their initial exposure levels and sacrificed at 24 hours. At each sacrifice, serum antibody to radiolabeled trimellityl rat serum albumin (RSA-TM) was measured by an ammonium sulfate technique, and lung pathology was determined. After 10 days of exposure, external hemorrhagic lung foci were directly related to the exposure concentration of TMA. Serum antibody binding of RSA-TM correlated with exposure concentration, hemorrhagic lung foci, and lung weight. There was healing of lung lesions 12 days after exposure with a return of lung lesions only 18 hours after the 6-hour inhalation challenge. A correlation between serum antibody to RSA-TM, hemorrhagic foci, and lung weight existed after challenge. This model clarifies two clinical entities observed in exposed workers, the late respiratory systemic and the pulmonary disease-anemia syndromes.

Administration, Inhalation↗
PubMed1987

Prevention of chymopapain anaphylaxis by screening chemonucleolysis candidates with cutaneous chymopapain testing. A preliminary report.

The risk of anaphylaxis in candidates for chemonucleolysis for herniated lumbar discs is approximately 1%. An investigation was designed to eliminate or reduce the incidence of chymopapain anaphylaxis. The procedure was to restrict chemonucleolysis to patients who are prick test-negative to chymopapain at a concentration of 10 mg/ml. The authors skin-tested 292 chemonucleolysis candidates; five were positive and 287 were negative. None of the positive patients were injected with chymopapain. There were no instances of unequivocal chymopapain anaphylaxis in the skin test-negative group. This 0% incidence of anaphylaxis in skin test-negative patients was compared with a population estimate of 1%, based on historical data. The resulting value of p = 0.08 value fell short of the conventional level of significance of 0.05. The p value will reach 0.05 when the series of skin test-negative patients without anaphylaxis reaches 360. It is important that this information is readily available to physicians concerned about anaphylactic reactions to chymopapain.

Adult↗
PubMed1987

Establishing clinical and immunologic criteria for diagnosis of occupational immunologic lung disease with phthalic anhydride and tetrachlorophthalic anhydride exposures as a model.

Using a questionnaire and serum antibody studies, we evaluated 13 workers exposed to phthalic anhydride (PA) and tetrachlorophthalic anhydride (TCPA). The questionnaire was designed to identify symptoms compatible with anhydride-induced immunologic or irritant syndromes. Specific IgG and IgE for both PA-human serum albumin (PA-HSA) and TCPA-HSA were determined by enzyme-linked immunosorbent assay in two different laboratories. In addition, 11 workers had cutaneous testing with PA-HSA and TCPA-HSA, and nine workers were interviewed. One worker was found to have PA-associated asthma and rhinitis. We conclude that a questionnaire and serologic assays for specific IgG and IgE are helpful to identify workers who have or are at risk for developing occupational immunologic lung disease such as those induced by anhydrides. However, additional evaluation may be necessary in those workers with such diseases as intrinsic asthma that may be difficult to differentiate from occupational immunologic lung disease.

Air Pollutants, Occupational↗
PubMed1986

Psychosomatic nasal disorder.

Present day allergy therapy can provide substantial symptomatic relief to patients with allergic and nonallergic rhinitis. Available measures are so effective that treatment failures with our most potent medications should raise the question of the presence of genuine pathology. Psychosomatic symptoms often involve nasal function. We present three such cases in which failure to relieve symptoms suggested a neurotic fixation on the condition of the nose and no demonstrable nasal pathology.

Adult↗