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Biomedical subjects

S Morrison

Publications and source records attributed to S Morrison.

At least 37 records · Page 2Linked to original sources
PubMed1998

Noncontact dipole effects on channel permeation. I. Experiments with (5F-indole)Trp13 gramicidin A channels.

Gramicidin A (gA), with four Trp residues per monomer, has an increased conductance compared to its Phe replacement analogs. When the dipole moment of the Trp13 side chain is increased by fluorination at indole position 5 (FgA), the conductance is expected to increase further. gA and FgA conductances to Na+, K+, and H+ were measured in planar diphytanoylphosphatidylcholine (DPhPC) or glycerylmonoolein (GMO) bilayers. In DPhPC bilayers, Na+ and K+ conductances increased upon fluorination, whereas in GMO they decreased. The low ratio in the monoglyceride bilayer was not reversed in GMO-ether bilayers, solvent-inflated or -deflated bilayers, or variable fatty acid chain monoglyceride bilayers. In both GMO and DPhPC bilayers, fluorination decreased conductance to H+ but increased conductance in the mixed solution, 1 M KCl at pH 2.0, where K+ dominates conduction. Eadie-Hofstee plot slopes suggest similar destabilization of K+ binding in both lipids. Channel lifetimes were not affected by fluorination in either lipid. These observations indicate that fluorination does not change the rotameric conformation of the side chain. The expected difference in the rate-limiting step for transport through channels in the two bilayers qualitatively explains all of the above trends.

Biophysical Phenomena↗
PubMed1998

Venous thromboembolism in trauma patients: standardized risk factors.

PURPOSE: This study was done to evaluate the use of published standardized risk factors for venous thromboembolism (VTE) in patients admitted to a trauma intensive care unit (ICU) and to derive guidelines for the use of low molecular weight heparin (LMWH) and surveillance venous Doppler ultrasound scanning (VDUS). METHODS: Patients were admitted to a regional trauma center ICU. Two periods were studied. Period 1 was a retrospective analysis of documented cases of VTE in the trauma registry from 1993 to 1995 (n=39). The period was also a review of all patients admitted to a trauma ICU in 1994 without VTE who met the following criteria: age greater than 11 years, ICU stay of more than 36 hours, and survival of more than 72 hours (n=227). Period 2 was a concurrent analysis of 1996 documented cases of VTE and similarly selected ICU admissions (VTE, n=10; no VTE, n=224). Risk factor scores (R1, admitting; R2, total) were calculated from the International Society for Cardiovascular Surgery/Society for Vascular Surgery reporting standards. The scores were cumulative by category and over time. The suitability of such standards was determined in period 1. The resulting therapeutic and surveillance guidelines were evaluated in period 2. RESULTS: Period 1 risk factor scores, R1 and R2, were correlated with the occurrence of VTE from chi2 test (P < .05 and P < .01, respectively). Risk categories were grouped as low, moderate, and high. VTE was not observed in the low-risk group (0 to 2). Among all VTE (n=49), 11 cases occurred in patients with moderate-risk scores and 38 in patients with high-risk scores. In 1994 and 1996, the selected groups were analyzed and the incidence rate of VTE was 4.7% in both years for the moderate-risk group and 2.5% and 4.8% for the high-risk group, respectively. Most VTE cases (78%) received some form of prophylaxis (PRx), and 26% of cases had multiple methods of prophylaxis (MPRx). This included 80% of the cases that received unfractionated heparin. In period 2, no pulmonary emboli (PE) occurred, in contrast to period 1, in which 16 of 39 cases of VTE (41%) were first seen with PE. In period 2, no patient receiving MPRx, including compression and LMWH, had VTE develop. Surveillance VDUS discovered 60% of 1996 cases in period 2. No PE were seen in period 2. CONCLUSION: Standard risk factors were easily applied to the trauma patient at the bedside. Patients at low risk needed no PRx. Patients at high risk did best with both compression devices and LMWH. VDUS was recommended selectively in patients at high risk in whom multiple-method PRx could not be achieved. Patients at moderate risk required further study to define optimal PRx and need for surveillance VDUS. Intracaval devices were used prophylactically only twice.

Adolescent↗
PubMed1998

Deposition of genetically engineered human antibodies into the egg yolk of hens.

To determine if human immunoglobulins (hIg) are capable of being transported into the hen's egg, 10 microg each of purified hIgG and hIgA were intravenously injected into SC Hyline(TM) hens and their presence in egg yolk and egg white was determined by ELISA. In both cases deposition into the egg yolk was observed and in the case of hIgA, deposition was also observed in the egg white. Two stably transfected DT40 cell lines secreting recombinant human IgG3 and IgA (rhIgG3 and rhIgA) were injected into laying hens. The DT40 cells colonized the host and rhIgG3 and rhIgA were deposited in egg yolk. Deposition of rhIgA was also observed in the egg white. These data demonstrate that human immunoglobulins and other foreign proteins may be targeted to the chicken's egg. In view of the high rate of reproduction, the short generation interval, the high rates of egg production and the extensive infrastructure to fractionate egg yolk proteins, it should be possible to produce large amounts of foreign protein in the eggs of transgenic chickens.

Animals↗
PubMed1997

Clinical and locus heterogeneity in brachydactyly type C.

Brachydactyly type C is characterized by shortness of the second and fifth middle phalanges and the first metacarpal. It is inherited as an autosomal dominant trait, and is noted for its widely variable clinical phenotype both within and between families. In most families involvement is limited to the hands. However, in some families additional skeletal and non-skeletal findings have been reported. We report on 12 affected members from a 5 generation kindred that segregates a brachydactyly type C phenotype. All affected individuals had shortness principally affecting the second and fifth phalanges and first metacarpal. However, the metacarpal-phalangeal profile indicated that other digital elements were short as well. In addition, one affected individual had a bilateral Madelung deformity, but none had foot involvement. No other non-skeletal findings cosegregated with brachydactyly in this family. Recently, a gene for brachydactyly type C has been localized to 12q24. This was done by studying a large kindred first reported by Haws [1963], which manifests both hand and foot anomalies. Here we present linkage data which excludes the 12q24 locus in our kindred, indicating locus heterogeneity as one explanation for the interfamilial variability described in brachydactyly type C.

Adolescent↗
PubMed1997

Effect of centrally administered endothelin agonists on systemic and regional blood circulation in the rat: role of sympathetic nervous system.

The aims of the present study were to determine (1) the hypotensive and regional circulatory effects of centrally administered endothelin (ET) ETA and ETB agonists, and (2) the role of the sympathetic nervous system in the mediation of hypotensive effects due to centrally administered ET-1. The systemic haemodynamics and regional blood circulation in urethane anaesthetized rats following intracerebroventricular (i.c.v.) administration of ET-1, ET-2, SRT6b, ET-3 and SRT6c (10, 30 and 90 ng) were determined by a radioactive microsphere technique. The effect of centrally administered ET-1 on sympathetic nerve activity was also analysed. Systemic haemodynamics and regional blood circulation were determined before (baseline) and 30 min after administration of ET agonists. Cumulative administration of three doses of saline (5 microliters, i.c.v. at 30 min intervals) did not produce any significant cardiovascular effects. ET-1, ET-2 and SRT6b produced a decrease in blood pressure (51%, 47% and 41%, respectively) along with a decrease in cardiac output (58%, 60% and 45%, respectively) and stroke volume. Heart rate and total peripheral resistance were not affected. ET-1, ET-2 and SRT6b also produced a significant reduction in blood flow to the brain, kidneys, heart, portal, mesentery and pancreas, gastrointestinal tract (GIT) and musculoskeletal system. The effect of ET-2 on the cardiovascular system was less intense in comparison with ET-1 and SRT6b. Centrally administered specific ETB receptor agonists ET-3 and SRT6c did not produce any change in systemic haemodynamics and regional blood flow. Centrally administered ET-1 (90 ng) produced a significant decrease (61%) in sympathetic nerve activity 30 min after drug administration, along with a fall in blood pressure. It is concluded that centrally administered ETA agonists produce significant cardiovascular effects mediating through the sympathetic nervous system.

Animals↗
PubMed1997

Effect of ETA receptor antagonists on cardiovascular responses induced by centrally administered sarafotoxin 6b: role of sympathetic nervous system.

The present study was carried out to investigate the cardiovascular effects of centrally administered SRT6b in saline, BQ123 and BMS182874 pretreated male Sprague-Dawley rats, using a radioactive microsphere technique. SRT6b (100 ng, ICV) produced a transient increase (40%) in blood pressure at 5 min followed by a sustained decrease (-42%) at 30 and 60 min in control rats. Total peripheral resistance and heart rate were not significantly altered. Cardiac output increased (16%) at 5 min and decreased 30 and 60 min following SRT6b administration. Central venous pressure was not affected by SRT6b. Regional blood flow and vascular resistance did not change at 5 min following administration of SRT6b. However, a significant decrease in blood flow to the brain, heart, kidneys, liver, spleen, gastrointestinal tract and mesentery and pancreas was observed 30 and 60 min following administration of SRT6b in control (saline treated) rats. Pretreatment with ETA selective receptor antagonists, BQ123 (10 micrograms, ICV) or BMS182874 (50 micrograms, ICV) significantly attenuated the pressor and depressor effects of centrally administered SRT6b. SRT6b induced decrease in blood flow was completely blocked by pretreatment with BQ123 or BMS182874. ET-1 (100 ng, ICV) produced an increase followed by a decrease similar to SRT6b. Reserpine (5 mg/kg, IP) pretreatment attenuated the cardiovascular effects of ET-1. Role of sympathetic nervous system was determined by measuring splanchnic nerve activity. SRT6b when administered in the lateral cerebral ventricle did not produce any significant effect at 5 min, however, a significant decrease in sympathetic nerve activity was observed 30 min after its administration. It is concluded that centrally administered SRT6b produces significant changes in systematic and regional blood circulation which can be completely blocked by ETA receptor antagonist. The cardiovascular effects of centrally administered SRT6b appear to be mediated through the sympathetic nervous system.

Animals↗
PubMed1996

Plasmacytoma development in mice injected with silicone gels.

Silicone gels derived from commercially obtained implants induce plasmacytomas in 60-70% of highly susceptible BALB/cAn.DBA/2-Idh1-Pep3 congenic mice. In contrast, dimethylpolysiloxane (DMPS) silicone oils with viscosities of 5, 1000 and 12,500 cs fail to elicit these tumors. 1000 cs vinylmethylpolysiloxane is also inactive. Silicone gels, in contrast to the oils, induce a highly inflammatory silicone granuloma. Silicone gels contain chemical components not found in the oils. The chemical component responsible for inducing the permissive environment for plasmacytoma formation has not yet been identified. Silicone gels are well tolerated for long periods of time in mice without adverse effects other than plasmacytoma formation. The response to different gel preparations varies; some are associated with relatively rapid formation of plasmacytomas resembling that seen with pristane, while in others the plasmacytoma formation is extended nearly over a two year period.

Animals↗
PubMed1996

Inter- and intra-limb coordination in arm tremor.

Inter- and intra-limb coordination in arm tremor was examined in adult subjects under vision and no vision conditions using accelerometery techniques. The accelerometer data were analyzed using standard time and frequency domain analyses and the regularity of the acceleration time series was determined using an approximate entropy (Ap En) measure. The data analysis was structured to examine the hypothesis that there is a functional compensatory relation between the motion (tremor) of the limb segments in the arm coordination postural pointing task. The results showed that the level of acceleration increased in a proximal to distal direction within a single arm and was symmetrical across homologous arm segments. The frequency analysis showed the established power spectral profiles for each limb segment in postural tremor tasks, but the finger motion included (beyond the normal 8-12 Hz and 20 Hz tremor) a third slower peak at around 2-3 Hz, due possibly to the reactive forces of the other arm links. There was no effect of vision on the level or frequency patterns of accleration in the limb segments. The coordination analysis showed that there was no linkage between the arms in either the time or frequency domain in the execution of this postural task. This result would tend to suggest that the neuronal commands underlying normal tremor are not derived from a common central oscillator within the central nervous system but are organized in a parallel fashion. The strength of the coupling of intra-limb coordination varied according to the particular adjacent limb links. There were significant correlations in the time domain and coherence in the frequency domain in the acceleration signals between upper arm and forearm, and between hand and finger. The phase lag of the arm units within each of these respective segment pairs was close to in phase or 0 deg. Significant coherence in the frequency domain was also evident between upper arm and hand motion, with the phase lag between these segments being close to 180 deg out of phase. The Ap En analysis of the acceleration signals revealed that there was more regularity to the upper arm and hand accelerometer signals than the forearm and finger signals. The findings show that the intra-limb coordination of the arm links in a two-limb postural pointing task is effected by a compensatory synergy organized about the action of the wrist and shoulder joints. This compensatory synergy reduces the coordination of the 4 within-limb degrees of freedom (arm links) to, in effect, a single degree of freedom arm control task that is not coupled in organization to the motion of the other limb or the torso. It is proposed that this coordination solution reduces the degrees of freedom independently regulated for realization of the task goal but preserves independent body segment control in critical degrees of freedom for potential adaptation to postural perturbations.

Adaptation, Physiological↗
PubMed1996

Anaesthetic management of labour and delivery in the parturient with mitochondrial myopathy.

PURPOSE: We describe the anaesthetic management for Caesarean section in a parturient with a defect in complex III of the respiratory chain who had increased lactate concentrations at rest and with exercise. CLINICAL FEATURES: We administered effective epidural anaesthesia with lidocaine for Caesarean delivery. The serum lactate concentration was less than the preoperative value both during and after surgery. Shivering during the perioperative period was avoided by administering warm i.v. fluids, warm local anaesthetic solution and epidural meperidine. Pain relief after surgery was provided with i.v. PCA morphine augmented by local infiltration with bupivacaine to fascia and skin edges and epidural injection with meperidine. CONCLUSION: Mitochondrial myopathies are an uncommon group of disorders in which mitochondrial dysfunction leads to clinical disease of muscle and sometimes of other organs with high energy requirements. The management of labour and delivery in women with mitochondrial myopathies should be individualized according to severity of disease and formulated by consultation between attending physicians and the anaesthetist. Epidural analgesia reduces stress and work associated with labour and reduces oxygen demand during labour. However, parturients with defects of the respiratory chain with documented increased lactate concentrations at rest and with exercise are best managed with elective Caesarean delivery with regional anaesthesia to prevent life-threatening lactic acidosis during labour. The association between malignant hyperthermia and these disorders has not been proved, but it appears prudent to consider these women as MH susceptible until definitive data regarding this possible relationship are available.

Adult↗
PubMed1996

Determinants of exercise capacity in patients with coronary artery disease and mild to moderate systolic dysfunction. Role of heart rate and diastolic filling abnormalities.

BACKGROUND: To test the hypothesis that diastolic filling abnormalities are an important cause of exercise limitation in some patients with coronary artery disease we assessed the factors limiting exercise capacity in a group of patients with coronary artery disease in whom exercise limitation was greater than expected from the degree of resting left ventricular systolic dysfunction. METHODS AND RESULTS: We assessed the relationship between exercise capacity (maximal oxygen consumption) during erect cycle ergometry, heart rate, radionuclide indices of left ventricular systolic function (ejection fraction) and diastolic filling (peak filling rate, and time to peak filling) during semi-erect cycle ergometry in 20 patients (15 male, five female) who were aged 42-72 years (mean 61 years) and had angiographically proven coronary artery disease and evidence of reversible myocardial ischaemia on thallium scintigraphy. All patients exhibited marked exercise limitation (maximal oxygen consumption 8.7- 22.4 ml.min-1.kg-1--mean 15.9 ml.kg-1.min-1, which was 61.1 +/- 16% of age and gender predicted maximum) due to breathlessness or fatigue rather than angina, in spite of a mean ejection fraction for the group of 46.5% (range 30-67%). We also compared the diastolic filling characteristics of these patients during exercise with 10 healthy controls (age 38-66, mean 58 years; eight male, two female). Comparing diastolic filling characteristics, peak filling rate was higher and time to peak filling shorter both at rest and at peak exercise in controls than patients (peak filling rate 3.1 +/- 0.5 vs 2.2 +/- 0.9 EDV.s-1, P = 0.01 at rest and 8.3 +/- 0.8 vs 5.2 +/- 1.9 EDV.s-1, P < 0.0001 on exercise; time to peak filling 115.2 +/- 29.8 vs 228.9 +/- 71.7 ms, P < 0.0001 at rest and 52.8 +/- 16.2 vs 139.6 +/- 44.8 ms, P < 0.0001 on exercise respectively). On univariate analysis in the patients studied, maximal oxygen consumption was correlated with peak heart rate (r = 0.45 P = 0.04), peak exercise time to peak filling (r = -0.85 P < 0.0001), peak exercise peak filling time rate (r = 0.51 P = 0.019), and the relative increase in cardiac output i.e. cardiac output peak/cardiac output rest (r = 0.58, P = 0.008). There was no correlation between maximal oxygen consumption and resting indices of diastolic filling (peak filling rate and time to peak filling) or with resting or peak exercise ejection fraction. On multiple regression analysis, only peak exercise time to peak filling was significantly related to maximal oxygen consumption. CONCLUSION: We have observed a strong correlation between exercise capacity and indices of exercise left ventricular diastolic filling, and have confirmed previous studies showing a poor correlation with resting and exercise indices of systolic function and resting diastolic filling, in patients with coronary artery disease.

Adult↗
PubMed1996

Custodial suicide in Australia: a comparative study of different populations.

Research on custodial suicide has run into immense difficulties in its attempt to identify common characteristics of the suicide-prone inmate. In 1993, Haycock recognized these difficulties and called for comparative research to delineate the different risks posed by different sorts of confined populations. This paper contrasts the characteristics of different categories of confined inmates based on data collected by the Australian Institute of Criminology on deaths in custody within Australia between the years 1980 and 1993, inclusive. This form of research will lead to a greater understanding of the phenomenon of custodial suicide and the establishment of better preventive strategies tailored to the needs of specific groups and organizations.

Adolescent↗
PubMed1996

Radiation exposure from diagnostic radiographs in extremely low birth weight infants.

OBJECTIVE: We sought to examine radiation doses received by infants of less than 750 g birth weight from radiographs. METHODS: We examined the radiology records, including radiograph films, of all 25 surviving infants with birth weight less than 750 g admitted to our center during 1991. The standard method of neonatal radiation dose calculation was modified to consider the body size, postnatal growth, and extramedullary hematopoiesis of the extremely low birth weight infant. To determine overall radiation exposure, we calculated an effective dose equivalent, which is the sum of weighed organ dose equivalents. RESULTS: The infants had a mean of 31 radiographys performed, including 17 chest radiographs, 5 babygrams, and 9 abdominal radiographs. The majority of chest radiographs and babygrams were performed in the first month, whereas abdominal radiographs increased during the second month of life. Total-body radiation dose and total effective dose equivalent by the standard and modified methods, respectively, for single exposures ranged from 0.01 to 0.02 millisieverts (mSv) for a chest radiograph, from 0.02 to 0.04 mSv for a babygram, and from 0.02 to 0.03 mSv for an abdominal radiograph. Surface organs icluding the skin, breast, and thyroid received the largest radiation doses. The effective dose equivalent per infant for all radiographs was 0.72 mSv according to the modified method, compared to a total-body dose of 0.40 mSv using the standard method. However, infants with chronic lung disease or necrotizing enterocolitis received up to 1.5 mSv total-body dose, including 3.3 mSv to the breast, 2.5 mSv to the thyroid, and 2.3 mSv to the testes. CONCLUSIONS: Radiation doses received by infants of less than 750 g birth weight are small in comparison with the range of doses that form the basis of risk estimates for cancer.

Body Constitution↗
PubMed1995

Induction of plasmacytomas in genetically susceptible mice with silicone gels.

Silicone gels injected intraperitoneally into strains of mice related to BALB/c develop plasmacytomas in approximately the same numbers and with similar phenotypes as previously obtained with pristane. Silicone gels produce few side effects and are well tolerated for long periods. Silicone gels contain several components that are potentially biologically active: residual vinyl groups and platinum. Microscopic and histological evidence suggests the silicone gel is degraded over a long period of time. Preliminary studies with long chain liquid dimethylpolysiloxanes with viscosities of 1000 cSt and 12,500 cSt have not produced plasmacytomas as yet. The plasmacytomagenic action of the gel appears to be due to the release of liquids from the gel matrix.

Animals↗
PubMed1994

Induction of plasmacytomas with silicone gel in genetically susceptible strains of mice.

BACKGROUND: Plasmacytomas can be induced in high frequency in susceptible strains of mice by the intraperitoneal introduction of plastics or paraffin oils, including the chemically defined oil pristane (2,6,10,14-tetramethylpentadecane). These materials persist in the peritoneal cavity, where they induce chronic inflammation during the long periods before plasmacytomas develop. Such plasmacytomas appear to arise from B cells carrying chromosomal translocations that affect c-myc transcription. PURPOSE: Because silicone gels are in widespread medical use and share many of the characteristics of other materials known to be inducers of plasmacytomas, we wished to determine their capacity to induce plasmacytomas in mice. METHODS: In a series of parallel experiments, corn oil, pristane, silicone oil (dimethylpolysiloxane), or silicone gel from commercially obtained mammary implants was injected intraperitoneally into plasmacytoma-susceptible BALB/cAnPt-A and congenic BALB/cAnPt.DBA/2-Idh1-Pep3 mice, as well as into plasmacytoma-resistant C57BL/6N, C3H/HeJ, DBA/2N, and (BALB/c x DBA/2)F1 mice. Mice were examined at least once every 2 weeks for signs of abdominal tumor or weight loss and screened every 4-6 weeks for peritoneal plasmacytoma cells by peritoneal lavage. Tissues were examined by histologic and immunohistochemical techniques. Metaphase chromosome spreads were made from ascitic plasmacytomas without Colcemid treatment, and metaphase plates were G-banded according to standard techniques. The t(12;15) or t(6;15) translocation chromosomes were identified under the microscope in at least five metaphase plates of high banding quality. Mice were autopsied 125-400 days after the injection of test material. Gas chromatography and mass spectrometry were utilized to determine the composition of the silicone oil and silicone gel used in the injections. RESULTS: The silicone gels tested induced plasmacytomas in BALB/cAnPt-A and BALB/cAnPt.DBA/2-Idh1-Pep3 mice. Neither corn oil used as a control nor 1000-centistoke or 12,500-centistoke dimethylpolysiloxane induced plasmacytomas in these mice. The plasmacytomas were transplantable in syngeneic hosts. Cytogenetic studies of 41 silicone-induced plasmacytomas showed that 30 had t(12;15) translocations, eight had t(6;15) translocations, and three had no translocations. CONCLUSIONS: The silicone gels used in mammary implants, which contain a complex mixture of different siloxanes, induced peritoneal plasmacytomas in genetically susceptible mice. Silicone gels provide new chemically defined materials that are effective inducers of plasmacytomas in BALB/cAnPt-A and BALB/cAnPt.DBA/2-Idh1-Pep3 mice. Further studies will be required to determine which of the components of these gels are the active materials.

Animals↗