Biomedical subjects
J Buchanan
Publications and source records attributed to J Buchanan.
Nifedipine reduces the increases in cerebral blood flow during hypercapnic episodes.
1. Cerebral blood flow (CBF) in the rat was monitored by a venous outflow technique with an extracorporeal circulation which allowed for continuous monitoring of flow over the several hours of the study. 2. Brief challenges with carbon dioxide (CO2) increased the CBF. 3. Nifedipine (1.00 mg/kg), a dihydropyridine calcium antagonist, attenuated the response of the animal to hypercapnia, while leaving the basal flow rate unchanged. 4. This study may have significant implications as to the effect of nifedipine on CBF. 5. Since similar results have been obtained with nifedipine in anoxia, this study suggests that the responses to anoxia and hypercapnia are interrelated and that the resulting hyperemia may be governed by the same mechanisms.
Acute gestational pyelonephritis: the impact on colloid osmotic pressure, plasma fibronectin, and arterial oxygen saturation.
Acute gestational pyelonephritis infrequently leads to nonhydrostatic permeability pulmonary edema known clinically as acute respiratory distress syndrome (ARDS). In this form of ARDS, sepsis is considered the primary cause of pulmonary dysfunction. Decreases in colloid osmotic pressure, plasma fibronectin, and arterial oxygen saturation are associated with a worsening prognosis in septic conditions. We sought to investigate the changes in these parameters with acute gestational pyelonephritis to gain insight into the factors that may place the patient at risk for sepsis-related morbidity. Colloid osmotic pressure, plasma fibronectin, and arterial oxygen saturation via pulse oximetry were prospectively measured during the inpatient treatment of 17 pregnant patients with acute gestational pyelonephritis. All three parameters achieved their nadir within 24 hours of hospitalization and the initiation of therapy. Although no patient developed significant pulmonary dysfunction, we believe that patient susceptibility for pulmonary edema and general morbidity could be maximal in the first 24 hours after therapy. Future studies using a larger number of patients may identify one or more of these laboratory parameters as helpful in identifying gravid patients who are at risk of developing gestational ARDS.
The molecular and structural basis of hearing impairment in mice with the cpk mutant gene.
We studied hearing impairment and cochlear ultrastructure in C57BL/6J mice containing the cpk mutant gene. Heterozygous cpk/+ mutant mice, 6-8 months old, showed a marked hearing loss as demonstrated by auditory evoked potentials with some showing hearing loss at 90 db sound pressure. Ultrastructural studies of first cochlear turn disclosed the absence of organs of Corti, no tissues on the basilar membrane, scanty spiral ganglia, normal tectorial membrane, and vacuolation of the stria vascularis. Reissner's membrane is normal at the endolymphatic side, but transparent at the perilymphatic side. In the second turn the organ of Corti are normal but Nuel's space is full of debris. The cpk mutant mice have hearing impairment perhaps due to deficiencies of genes expressing vital basement membrane components.
Effects of ryanodine and BAY K 8644 on membrane properties and conduction during simulated ischemia.
We studied the effect of 1.0 microM ryanodine and 0.1 microM BAY K 8644 (putative modulators of intracellular calcium) on the changes in action potential characteristics, cellular coupling, and longitudinal conduction induced by simulated ischemia (9.0 mM K, 6.5 pH, 0 glucose, 20 mmHg PO2) in superfused guinea pig papillary muscles. Simulated ischemia (SI) depolarized the resting membrane by 5 mV and caused a 28% decrease in action potential upstroke (Vmax), a 65% decrease in action potential duration at 90% (APD90), a 40% increase in internal longitudinal resistance (ri), and a 17% decrease in conduction velocity as compared with the 9-K Tyrode control solution. These changes were reversible and reproducible. The decrease in Vmax induced by SI was greater than that associated with a K(+)-induced change in resting membrane potential (RMP). Ryanodine lessened the SI-induced APD90 shortening by 26%, the decrease in Vmax by 42%, the increase in ri by 33%, and the decrease in conduction velocity by 21%. BAY K 8644 did not alter SI-induced APD90 shortening but augmented the decrease in Vmax by 23%, the increase in ri by 67%, and the decrease in conduction velocity by 59%. Neither ryanodine nor BAY K 8644 altered the SI-induced changes in RMP. Our results suggest that changes in intracellular calcium during SI not only influence cellular coupling but also contribute to the apparent non-RMP-dependent component of the change in Vmax and to the change in APD90 induced by SI.
Medical education in palliative care.
There has been recent concern about both the care of dying patients and the adequacy of the preparation that most doctors receive for this task. The role of the doctor in palliative care is discussed and the educational needs of medical students in palliative care are suggested. A palliative care course for fifth-year students at the Austin Hospital-Repatriation General Hospital Clinical School, University of Melbourne, is described. This course recently has been adopted by the Victorian Palliative Care Council as a model for undergraduate palliative medicine education, and has been recommended to the University of Melbourne and Monash University Medical Schools for incorporation in each Clinical School curriculum.
Contractions of the squid stellate ganglion.
Optical recording methods were used to characterize the intrinsic movements of squid stellate ganglia. Ganglionic contractions were rhythmic and occurred at a mean frequency of 8 min-1. Contractions were eliminated when Na+ in the external saline were replaced by Tris, but were only slowed when Na+ was replaced by sucrose. This suggests that Na+ plays some role in generating the contractions, but the complete abolition produced by Tris-containing saline may be due to a secondary pharmacological action of this ion. The Na+ channel blocker, tetrodotoxin, had no effect on contractions. Contractions were eliminated by removal of external Ca2+, by treatment with the inorganic Ca2+ channel blockers Mn2+ and Cd2+, or by treatment with the organic dihydropyridine Ca2+ channel blockers nitrendipine and nimodipine. Thus, extracellular Ca2+ plays an important role in generating the contractions. Because dihydropyridines eliminate contractions, but not synaptic transmission, they offer a means of studying transmission at the giant synapse of the stellate ganglion without having to contend with ganglionic movement. Electron microscopy of stellate ganglia revealed the presence of two types of cell that contained the organized arrays of cytoskeletal elements usually associated with contractile cells. One type was a pericyte that surrounded blood vessels within the stellate ganglion. The second type was distributed throughout the ganglion and resembled a smooth muscle cell. Either of these cell types might generate ganglionic contractions.
Drug information services at Genentech.
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Part I: The NGRI Registry: initial analyses of data collected on Connecticut insanity acquittees.
The NGRI Registry is a comprehensive census database collected by the Law and Psychiatry Division of the Department of Psychiatry at the Yale University School of Medicine. This longitudinal database was compiled following a systematic search of all available docket books from the superior courts and mental health records from the state hospitals in Connecticut beginning in January 1970. Detailed life span information is available for 364 insanity acquittees identified during the search. Comparative analyses with four other locales suggested that there were regional differences in diagnoses of and crimes committed by the acquittees. These initial analyses demonstrate the promise of this registry becoming one tool for collaborative research on issues relevant to law and mental health.
Differential effects of gonadal function on bone histomorphometry in male and female rats.
The effects of castration on bone histomorphometry and mineral homeostasis were compared in male and female rats. Measurements were performed 4 weeks after sham operation or gonadectomy. Orchiectomy produced increases in serum calcium and decreases in serum testosterone and androstenedione, whereas ovariectomy produced decreases in serum estradiol and testosterone. Orchiectomy did not alter static bone histomorphometric measurements of the tibial diaphysis, whereas ovariectomy increased cross-sectional and medullary areas, lowered endosteal tetracycline-labeled surface length, and markedly increased endosteal nonlabeled surface length. Orchiectomy decreased mean periosteal bone formation rate and mean periosteal bone apposition rate, whereas ovariectomy increased both measurements. Orchiectomy and ovariectomy markedly diminished trabecular area and trabecular surface length at the tibial metaphysis. Orchiectomy did not alter the number of osteoclasts per mm trabecular surface or the percentage of trabecular surface covered by osteoclasts, whereas ovariectomy increased both measurements. These findings indicate that gonadal hormones produce separate and distinct effects on bone metabolism as determined by histomorphometry in male and female rats.
A case of pulmonic stenosis with single coronary artery in a dog.
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Studies of nerve-muscle interactions in Xenopus cell culture: fine structure of early functional contacts.
We have studied the fine structure of nerve-muscle contacts during the first few hours of synaptogenesis in embryonic Xenopus cell cultures. The precise timing of contact was achieved by manipulating isolated spherical myocytes (myoballs) into contact with growth cones or neurites of co-cultured spinal neurons. The contacts were shown to be functional by whole-cell voltage-clamp recording of nerve-evoked synaptic currents in the muscle cell. The ultrastructure of these functional contacts was examined by thin-section electron microscopy. In total, 20 nerve-muscle pairs were studied with contact periods ranging from 20 min to 12 hr, during which time a substantial increase in the amplitude of synaptic currents occurred. The structure of noncontacting cells and of nerve-muscle contacts formed between the cells by natural encounters in 1-d-old cultures were also examined in order to identify the features and the time course of morphological differentiation of early functional contacts. Prominent features of the contact area during the first few hours included: close apposition of the nerve and muscle membranes, greater frequency of coated pits and vesicles, and thickening of postsynaptic muscle membrane. Occasionally, clusters of clear vesicles occurred near presynaptic membrane, but no further sign of active zone differentiation was observed. In comparison, definitive active zone structure, well-formed extracellular basal lamina, and widened cleft were seen in natural contacts less than 24 hr old. This study of the identified functional contacts may help us to understand the structural basis for early nerve-muscle interaction and the functional significance of various synaptic specializations.
Noradrenaline-containing transplants in the adult spinal cord of mammals.
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Effect of graded coronary flow reduction on ionic, electrical, and mechanical indexes of ischemia in the pig.
This study was performed to determine the relative sensitivities of ionic, electrical, and mechanical indexes of myocardial ischemia. We used ion-selective and bipolar plunge electrodes, epicardial unipolar electrodes, a suction electrode, and ultrasonic crystals to determine the changes in intramyocardial extracellular potassium ([K+]e) and extracellular pH (pHe), local activation, epicardial TQ-ST segment, monophasic action potential duration (MAPD), and regional contractility during graded coronary flow reduction in open-chest pigs. A carotid-to-coronary shunt was created to perfuse the left anterior descending coronary artery via a roller pump. The shunted coronary flow was reduced in a stepwise fashion at 5-min intervals. In 25 pigs, the approximate myocardial blood flow associated with the initial changes in each variable was as follows: midmyocardial [K+]e, pHe, and TQ-ST segment, 0.7 to 0.8 ml/min/g; subepicardial [K+]e and TQ-ST segment, 0.6 to 0.7 ml/min/g; segmental shortening, 0.5 to 0.6 ml/min/g; local activation and epicardial TQ-ST segment, 0.3 to 0.4 ml/min/g; epicardial MAPD, 0.15 to 0.2 ml/min/g. Our results indicate that changes in [K+]e, pHe, and TQ-ST segment provide the most sensitive means of detecting myocardial ischemia and of determining the effect of interventions capable of influencing the ischemic process.
Disability and the built environment.
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A report from an Interdisciplinary Conference on Mental Health and Aging.
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Practical management of cancer pain.
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Gamma-aminobutyric-acid deficiency in brain of schizophrenic patients.
Gamma-aminobutyric acid (G.A.B.A.) was measured in the nucleus accumbens and thalamus of brains from patients who had died with schizophrenia or Huntington's chorea (H.C.) and from control subjects. Mean G.A.B.A. content was significantly reduced in both brain areas in schizophrenia and in H.C. Extraneous factors, such as age, interval from death to necropsy, cause of death, and drug use, did not readily explain the observed reduction in brain G.A.B.A. G.A.B.A. deficiency may be a biochemical characteristic of some forms of schizophrenia.