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Biomedical subjects

R Simons

Publications and source records attributed to R Simons.

At least 19 recordsLinked to original sources
PubMed1997

Hypoxic syncope.

INTRODUCTION: Syncope at altitude of otherwise healthy individuals is a well-known phenomenon (22). We report on the cardiovascular effects observed in subjects exposed to hypoxia to illustrate the role of the sympathetic-adrenergic system in hypoxic syncope. This study describes unexpected episodes of (near) syncope during two crossover trials at simulated altitude in a low pressure chamber. METHODS: In study A, 30 healthy male volunteers underwent 4 exposures to short-term (20 min) acute severe hypoxia (20,000 ft or 6096 m) to assess psychological performance. In study B, five volunteers were studied during prolonged exposure (1 h) to moderate hypoxia (13,500 ft or 4115 m) with and without concomitant low dose infusion with atrial natriuretic peptide to investigate the effects on pulmonary gas exchange. RESULTS: In study A (acute severe hypoxia), 6 out of 120 exposures (5%), in 5 subjects, were accompanied by lightheadedness, pallor, sweating, and bradycardia. Two subjects (2%) had syncope with cardiac asystole. In study B during moderate hypoxia without atrial natriuretic peptide, adverse reactions were absent and the (nor)epinephrine levels remained unchanged. Concomitant infusion with atrial natriuretic peptide resulted in near syncope (recumbent in 3, standing in 2) at an oxygen saturation of 82%. While the epinephrine level had eightfold increased, mean arterial pressure fell from 94 to 40 mm Hg and heart rate from 79 to 44 bpm. The norepinephrine level remained unchanged illustrating a dissociated sympathetic-adrenergic response. All subjects with syncope recovered spontaneously within few minutes in Trendelenburg's position with oxygen supplied. None suffered from prolonged side effects. CONCLUSION: It is concluded that exposure to acute severe hypoxia is a sufficient cause for syncope in healthy individuals. Enhanced vasodilatation to epinephrine may contribute to the withdrawal of sympathetic and enhancement of parasympatic activity, leading to vascular collapse, bradycardia or asystole (Bezold-Jarisch reflex). Patients fully recover in Trendelenburg's position with supplemental oxygen and further clinical examinations are not necessary.

Adult↗
PubMed1996

The ongoing challenge of retroperitoneal vascular injuries.

BACKGROUND: Retroperitoneal vascular injury remains one of the most frequent causes of death following abdominal trauma. A risk analysis of the association between potential outcome predictors and mortality following abdominal aorta and inferior vena cava injuries was performed. METHODS: Eighty-nine patients sustaining abdominal aortic or inferior vena cava injury were concurrently evaluated for a 10-year period and retrospectively reviewed. A multiple logistic regression model evaluated the following variables:presence of shock on admission, base deficit (< -10 or > or = -10), classification by the organ injury scale (OIS), blood transfusion, crystalloid infusion, total infusion volume, associated injuries, site of injury, and presence of retroperitoneal tamponade. RESULTS: Overall mortality for all injuries was 57%. Excluding all death on arrival (DOA) patients, the mortality rate decreased to 45.7%. Death following abdominal aortic injuries was significantly associated with free bleeding in the peritoneal cavity, acidosis, and an injury in the suprarenal location (OIS > 4). For inferior vena cava injuries and combined abdominal aortic and inferior vena cava injuries, death was associated with free bleeding, the suprarenal location (OIS = 4), and the presence of shock on admission as well. CONCLUSIONS: Despite advances in transport and resuscitation, mortality of aortic and vena cava injuries remains unchanged. Shock on admission, bleeding without retroperitoneal tamponade, acidosis, and the suprarenal location each play a significant role in mortality. Immediate identification associated with a rapid surgical approach are the only factors that may improve survival of such devastating injuries.

Adolescent↗
PubMed1995

[Bungi jumping].

Explore the source record for details and available documents.

Acceleration↗
PubMed1995

Hypoxia-induced arterial endothelin does not influence peripheral vascular tone.

The effect of hypoxia (SpO2 80%) on the arteriovenous production of endothelin-1 (ET) in the forearm was investigated in six healthy volunteers. In eight other subjects the local vascular effects of a low physiologic dose of intra-arterially administered ET (0.5 pg/kg/min) was studied during normoxia. Forearm blood flow (FBF) was measured by venous occlusion plethysmography, and arterial and venous plasma concentrations of ET were measured. FBF was not significantly influenced during hypoxia. After 15 min of hypoxia the arterial plasma level of ET increased from 2.5 +/- 0.1 to 3.3 +/- 0.3 ng/L (p < 0.05), whereas the venous plasma level remained unchanged. Intra-arterial infusion of ET increased the arterial plasma level of ET in the forearm from 2.2 +/- 0.3 to 4.9 +/- 0.4 ng/L. This increase in ET concentration did not influence FBF. It is concluded that hypoxia is a stimulus for ET release from the pulmonary vascular bed and that the resulting increase arterial plasma ET level does not influence peripheral vascular tone.

Adult↗
PubMed1993

In-house board-certified surgeons improve outcome for severely injured patients: a comparison of two university centers.

The benefit derived from in-house board-certified attending surgeons (IHBCS) staffing trauma centers has recently been questioned. We compared the outcomes and provider-related complications of patients with severe injuries who were treated at two university trauma centers, one with IHBCS, and one with PGY-4 or PGY-5 residents in house (RIH). The RIH center had a significantly longer resuscitation time (160 vs. 58.8 minutes; p < 0.01). Except in cases of vascular injury, the odds ratio of dying at the RIH institution was significantly greater in all groups when the variables of transport time, Revised Trauma Score, and ISS were controlled. Errors in judgment were significantly more likely to have been made at the RIH institution in all groups. It is concluded that the management and ultimate outcome are significantly improved when IHBCS are involved with the resuscitation and early care of specific cohorts of severely injured patients.

Adult↗
PubMed1993

Atrial natriuretic peptide improves pulmonary gas exchange in subjects exposed to hypoxia.

Atrial Natriuretic Peptide (ANP) is secreted in response to hypoxia and pulmonary vasoconstriction. The hormone modulates pulmonary vascular tone in vivo and decreases pulmonary edema in isolated lungs exposed to several toxic agents. In addition, ANP improves the barrier function of endothelial cell monolayers in vitro. The plasma levels of ANP are elevated in patients with high-altitude pulmonary edema. We hypothesized that under these circumstances, ANP improves pulmonary gas exchange by attenuating the transvascular permeation of plasma (water). Therefore, we studied the effect of low-dose ANP in 11 healthy mountaineers exposed to hypoxia in a single-blind, placebo-controlled, cross-over design. During four 1-h periods, the subjects were stepwise exposed to decreasing barometric pressure, with a minimum of 456 mm Hg (simulated altitude, 4,115 m). Infusion of 5 ng/kg/min human-ANP increased the plasma ANP concentrations approximately twofold. The plasma concentrations of cyclic GMP, which is the second messenger of ANP, rose approximately threefold. Infusion of ANP did not affect the hemodynamic or ventilatory response to hypoxia. The hemoglobin concentration, however, rose from 9.0 +/- 0.1 to 9.4 +/- 0.1 mmol/L (p < 0.01) during ANP infusion but not during placebo infusion. The change in plasma volume calculated from this hemoconcentration indicated that approximately 10% of the plasma volume had permeated into the interstitium. Despite the observed whole-body hemoconcentration, oxygen saturation was significantly higher during ANP infusion than during placebo infusion (84.7 +/- 1.7 versus 79.6 +/- 1.8%, p < 0.05), and the alveolar-arterial oxygen difference was significantly lower (3.5 +/- 0.7 versus 7.3 +/- 0.8 mm Hg, p < 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1990

The myelin-deficient rat has a single base substitution in the third exon of the myelin proteolipid protein gene.

Several genetic disorders that occur in animals and in humans result in an inability to synthesize normal myelin. Some of these disorders are inherited in an X-linked manner. The localization of the myelin proteolipid protein (PLP) gene to the X chromosome has directed the study of X-linked myelination disorders toward PLP. The myelin-deficient rat is one such X-linked dysmyelinating mutant. From a cDNA library constructed from myelin-deficient rat brain mRNA, we have isolated and sequenced cDNAs corresponding to PLP and its alternatively spliced isoform, DM-20. An A to C transition was detected in these cDNAs, which results in a threonine to proline change at amino acid 74 in both PLP and DM-20. No other substitutions were seen in the cDNA sequences. Polymerase chain reaction amplification and sequencing of the corresponding genomic regions were used to confirm the single base change. This substitution occurs in a highly hydrophobic portion of the protein that is thought to be an alpha-helical transmembrane segment. The presence of a helix-breaking amino acid such as proline in this segment is likely to influence the ability of the protein to interact with the membrane.

Animals↗
PubMed1990

Single base substitution in codon 74 of the MD rat myelin proteolipid protein gene.

The myelin-deficient (md) rat is one of several X-linked animal mutants that have severe dysmyelination in the central nervous system. It appears in all to be the result of mutations in the myelin proteolipid protein gene which is located on the long arm of the X-chromosome. To identify the md rat mutation, we isolated and sequenced cDNAs corresponding to PLP and DM-20 mRNAs from the brain of hemizygous affected males. The only consistent sequence difference between these and normal rat sequences was the substitution of a C for an A at the first position of codon 74, resulting in a threonine to proline amino acid change. The presence of this helix-breaking amino acid in the second hydrophobic alpha-helical segment of the protein might be expected to influence its ability to interact with the membrane. PCR amplification and sequencing of the corresponding genomic regions were used to confirm the presence of the single base change in the hemizygote and both normal and mutant versions in the heterozygotes. It is interesting that this change, like those detected in other X-linked myelin disorders, involves an amino acid replacement within a hydrophobic alpha-helical segment of the PLP protein. Disruption of these structures apparently has severe consequences for the ability of PLP to contribute normally to myelination.

Aging↗
PubMed1988

Mercury localization in mouse kidney over time: autoradiography versus silver staining.

Several methods of silver staining have been employed to localize mercury in tissue, under the assumption that the techniques represent total Hg, but recent reports have suggested that these stains are specific for a limited fraction of the Hg present in some samples. Magos et al. (1985, Arch. Toxicol. 57, 260-267) hypothesized that the stains actually vary with inorganic mercury content. The purpose of the present study was to compare localization by radiolabeling to localization by one silver stain, the photoemulsion histochemical technique, in tissues prepared to contain a range of levels of total Hg and a range of levels of inorganic Hg. Mice dosed with 8 mg Hg/kg as MeHg were killed 24 hr, 1 week, or 2 weeks after exposure, to allow a decrease in total Hg and an increase in the proportion of demethylated Hg over time. Mice dosed with 4 mg Hg/kg as HgCl2 provided samples in which all the Hg present was in the inorganic form. Atomic absorption of kidneys of mice dosed with MeHg showed that total Hg fell from 55 micrograms/g to 39 to 25 over 2 weeks, while the inorganic fraction climbed from about 2 to 27 to 35%. Grain counts from autoradiographs of 203Hg-labeled sections correlated with total Hg content at +0.88, but silver staining was correlated with inorganic Hg content, appearing only at late termination times in MeHg-exposed animals, but soon after dosing in mice exposed to inorganic Hg. The photoemulsion histochemical technique revealed a substance strictly localized in the proximal tubules, while autoradiographs and grain counts showed total Hg to be present throughout the kidney tissue. These results support the contention that silver stains are selective for inorganic Hg and suggest that the distribution of inorganic Hg, whether introduced experimentally or by gradual demethylation, is different from the distribution of MeHg. If subsequent studies support the association of silver stains with inorganic Hg, it should be possible to localize Hg in histologic sections, distinguishing between organic and inorganic forms, which differ in toxicity.

Animals↗
PubMed1987

Human myelin DM-20 proteolipid protein deletion defined by cDNA sequence.

Using a myelin proteolipid protein (PLP) cDNA as probe, a 1kb cDNA was isolated from a human retinal cDNA library. This clone, designated pDM-20, contained all of the coding sequence of PLP except for 105 base pairs which encode amino acids 117-151 of PLP. This deletion would result in a protein of the size of DM-20, the second major proteolipid of Central Nervous System (CNS) myelin. Homology between the DNA sequence at the 5' end of the deletion and the donor splicing consensus sequence suggests that PLP and DM-20 transcripts are derived from a single PLP gene by alternate splicing.

Amino Acid Sequence↗
PubMed1982

Transposon Tn10: genetic organization, regulation, and insertion specificity.

Transposon Tn10 is a composite element in which two individual insertion sequence (IS)-like sequences cooperate to mediate transposition of the intervening material. The two flanking IS10 elements are not identical; IS10-right is responsible for functions required to promote transposition, and IS10-left is defective in transposition functions. We suggest that the two IS10 elements were originally identical in sequence and have subsequently diverged. IS10-right is compactly organized with structural gene(s), promoters, and sites important for transposition and (presumably) its regulation all closely linked and, in some cases, overlapping. IS10 has a single major coding region that almost certainly encodes an essential transposition function. A pair of opposing promoters flank the start of this coding region. One of these promoters is responsible for expression in vivo of transposon-encoded transposition functions. We propose that the second promoter is involved in modulation of Tn10 transposition. Genetic analysis suggests that transposon-encoded function(s) may be preferentially cis-acting. Insertion of Tn10 into particular preferred target sites is due primarily to the occurrence of a particular six-base pair target DNA sequence. The properties of this sequence suggest that symmetrically disposed subunits of a single protein may be responsible for both recognition and cleavage of target DNA during insertion.

Base Sequence↗
PubMed1981

Strategies of arousal control: biofeedback, meditation, and motivation.

A series of four experiments assessed the effects of instructions to lower heart rate on heart rate change and general arousal reduction. Various conditions of biofeedback, cognitive load, incentive, knowledge of results, and the experimenter-subject relationship were tested. Experiment 1 compared physiological responses to the delivery of direct organ feedback (i.e., heart rate) with responses to electromyographic biofeedback from the frontalis muscle area and with responses to a nonfeedback tracking task. The results suggest that neither heart rate nor muscle tension feedback is an especially powerful method for achieving sustained reductions in heart rate. Furthermore, although some specificity of physiologic pattern is apparent, biofeedback is no more effective in lowering general activation level than simple instructions to relax accompanied by a general knowledge of results. The second experiment was designed to assess the role of cognitive load in arousal reduction. Heart rate biofeedback was compared with a procedure involving minimal external information processing--the secular meditation exercise of Wallace and Benson. The results indicated a clear superiority for the meditation strategy in effecting reductions in cardiac rate and lowering activation. However, in a third experiment, meditation subjects lowered heart rate much less than observed in the previous study, and this time the reduction did not exceed that achieved by feedback subjects. Subsequent analysis suggested that the quality of the subject-experimenter relationship (active-supportive vs. formal-distant) was a significant variable in accounting for outcome differences. The above hypothesis was supported by a fourth experiment. Under conditions of high subject-experimenter involvement, the superior meditation performance of Experiment 2 was reproduced; under low-involvement conditions the Experiment 3 result of no difference between training groups was obtained. The findings suggest that the effectiveness of any method for achieving relaxation (or physiological control) rests on a complex interaction between informational and motivational imperatives of the stimulus context and definable aspects of the interpersonal exchange between subject and experimenter. This research raises serious questions about the effectiveness of the usual biofeedback paradigm as an aid to arousal reduction and the cost efficiency of its applications in the clinical situation. Furthermore, these results demonstrate the great power in relaxation experiments of psychosocial and other moderator variables, and signal the practical difficulty of their control when these variables appear to be as potent in changing physiology as the primary training methods.

Arousal↗
PubMed1980

Enhancement of activity against influenza viruses by combinations of antiviral agents.

In an investigation of alternative therapeutic approaches for the treatment of influenza virus infections, the antiviral activities of rimantadine hydrochloride, amantadine hydrochloride, ribavirin, and combinations of these drugs were assessed in vitro. Madin-Darby canine kidney cell monolayers were inoculated with recent isolates of influenza viruses at low multiplicities of infection, and virus titers were determined after 24 h. The combination of rimantadine and ribavirin resulted in an enhanced antiviral effect (a decrease in virus titer of > 1.0 log10 plaque-forming unit per ml at 24 h relative to the maximal effect of a single drug) against A/USSR/90/77/H1N1, A/Texas/1/77/H3N2, A/New Jersey/76/HSW1N1, and A/PR/834/H0N1 viruses. The degree of inhibition depended on the virus strain used, the drug concentrations, and the virus inoculum. Amantadine and ribavirin showed enhanced activity. Ribavirin in combination with high (50 micrograms/ml), but not low (1.56 to 25 micrograms/ml), concentrations of rimantadine showed an enhanced antiviral effect against B/Hong Kong/72 virus. An assay of Madin-Darby canine kidney cell proliferation in the presence of drugs showed that the enhanced inhibitory effect of drug combinations was not due to increased cytotoxicity.

Antiviral Agents↗