Biomedical subjects

D Gendron

Publications and source records attributed to D Gendron.

At least 19 recordsLinked to original sources

PubMed2002

The effects of hemodilution with Hemolink upon hemodynamics and blood flow distribution in anesthetized dogs.

Hemoglobin based oxygen-carrying solutions (HBOCs) as hemoglobin replacement therapeutics are being tested for clinical use. Some of these products are associated with elevations in both systemic and pulmonary vascular resistances but their effect on the distribution of blood flow to major organs in larger animals have not been extensively described. We tested two formulations of o-raffinose cross-linked human hemoglobin, Hemolink (frozen-Hemolink-1 and refrigerated Hemolink-2) and compared them to Pentaspan, a colloid volume expander in extensive clinical use. Cardiovascular measurements and the distribution of blood flow (radionuclide-labeled microspheres) to the major organs were determined in Beagle dogs (n = 5 per group). After baseline measurements, either Hemolink-1, Hemolink-2, or Pentaspan was exchange transfused in an isovolemic manner (resulting in hematocrit reduction to approximately 20-25%); measurements were made 30, 60, 120 and 180 min post-exchange. There was no significant difference in cardiac output, mean arterial pressures and systemic or pulmonary vascular resistances after exchange in any of the three groups. Myocardial blood flow increased in all three groups post-exchange but the increase was more sustained in the Hemolink groups. Endocardial/epicardial flow ratios were also maintained after exchange in all groups. Thus, Hemolink is ideally suited for volume replacement when used in conjunction with acute normovolemic hemodilution because under these circumstances, the adverse hemodynamic effects are alleviated while extra hemoglobin is added to the blood.

Anesthesia↗

PubMed2001

Structure formation and instability in a tube of sand.

A new instability in the combined flow of fine grains and gas is investigated by means of experiments, simulations, and analytic techniques. When a bubble of air rises through a granular packing in a tube, a sequence of smaller bubbles spontaneously forms in front of it. The existence of this instability is shown from the experiments, simulations, and theoretical considerations. Moreover, the simulations and experiments agree on the quantitative level. In particular, when the tube is tilted away from the vertical the experiments and the simulations show the same increase in the speed of the rising bubble.

Journal Article↗

PubMed2001

Bubble propagation in a pipe filled with sand.

Granular flow with strong hydrodynamic interactions has been studied experimentally. Experiments have been carried out to study the movement of a single bubble in an inclined tube filled with glass beads and air. A maximum bubble velocity was found at an inclined angle straight theta(m). The density variations in the sand were measured by capacitance measurements, and a decompactification zone was observed just above the bubble when the inclination angle straight theta was larger than straight theta(m). The length of the decompactification front increased with increasing inclination angle and disappeared for angles smaller than straight theta(m). Both pressure and visualization experiments were carried out and compared with the density measurements.

Journal Article↗

PubMed2001

Upper airway sensation in snoring and obstructive sleep apnea.

Previous studies indicate that upper airway (UA) sensory receptors play a role in the maintenance of UA patency and contribute to arousal in response to airway occlusion. An impairment of UA sensory function could therefore predispose to UA obstruction during sleep. We hypothesized that UA sensation is impaired in obstructive sleep apnea (OSA), and that sensation improves after treatment with nasal continuous positive airway pressure (CPAP). We measured two-point discrimination (2PD) and vibratory sensation thresholds (VT) in 37 patients with OSA (mean [+/- SE] apnea- hypopnea index [AHI] = 39 +/- 5 events/h), 12 nonapneic snorers (SN), and 15 control subjects (CL). Sensory thresholds were determined in the UA and on the lip and hand as control sites. Both 2PD and VT were similar among the three groups at the lip and hand sites but were significantly reduced in the UA of OSA and SN subjects versus CL (p < 0.05). Values for 2PD and VT in the UA of OSA versus SN were not significantly different. Sensory measures were repeated after 6 mo in 23 OSA patients treated with CPAP as well as in 18 untreated patients. Thresholds for 2PD and VT at control sites remained identical in both groups, as did 2PD for the UA. However, VT in the UA showed a significant improvement in treated (4.4 +/- 0.2 pre-CPAP versus 3.8 +/- 0.2 mm post-CPAP, p < 0.05) but not untreated patients. These findings indicate the presence of a selective impairment in the detection of mechanical stimuli in the UA of patients with OSA and SN, which is partially reversible after treatment with nasal CPAP in patients with OSA.

Adult↗

PubMed2001

The gene encoding the major viral structural protein stimulates recombination in polyomavirus DNA.

RmI is a chimeric DNA molecule consisting of a polyoma genome in which a partly duplicated VP1-coding region brackets an insert of murine DNA (Ins); when transfected into mouse cells, RmI recombines intramolecularly to yield infectious, unit-length, polyoma DNA. We report here that RmI encodes a polypeptide of 337 amino acids (designated VmP1) which includes the N-terminal 328 amino acids of VP1 and 9 amino acids specified by Ins. Mutating the VmP1-coding sequence strongly reduces the ability of RmI to yield polyoma DNA. In contrast, mutating the portion of the VP1-coding sequence which is not part of the VmP1-coding sequence has little or no impact on the ability of RmI to yield polyoma DNA, even though it renders such DNA noninfectious. Thus, release of polyoma DNA from RmI involves a function of VP1 distinct from that ensuring virus assembly and propagation; since VP1 can arise only after recombination has occurred, VmP1, but not VP1, could carry such a function. We suggest that VmP1 acts in concert with VP2, which we have already reported to stimulate recombination in RmI.

Amino Acid Sequence↗

PubMed2001

The effects of hemodilution with Hemolink upon hemodynamics and blood flow distribution in anesthetized dogs.

Hemoglobin based oxygen-carrying solutions (HBOCs) as hemoglobin replacement therapeutics are being tested for clinical use. Some of these products are associated with elevations in both systemic and pulmonary vascular resistances but their effect on the distribution of blood flow to major organs in larger animals have not been extensively described. We tested two formulations of o-raffinose cross-linked human hemoglobin, Hemolink (frozen Hemolink-1 and refrigerated Hemolink-2) and compared them to Pentaspan, a colloid volume expander in extensive clinical use. Cardiovascular measurements and the distribution of blood flow (radionuclide-labeled microspheres) to the major organs were determined in Beagle dogs (n=5 per group). After baseline measurements, either Hemolink-1, or Hemolink-2, or Pentaspan was exchange transfused in an isovolemic manner (resulting in hematocrit reduction to approximately 20-25%); measurements were made 30, 60, 120 and 180 min post-exchange. There was no significant difference in cardiac output, mean arterial pressures and systemic or pulmonary vascular resistance after exchange in any of the three groups. Myocardial blood flow increased in all three groups post-exchange but the increase was more sustained in the Hemolink groups. Endocardial/epicardial flow ratios were also maintained after exchange in all groups. Thus, Hemolink is ideally suited for volume replacement when used in conjunction with acute normovolemic hemodilution because under these circumstances, the adverse hemodynamic effects are alleviated while extra hemoglobin is added to the blood.

Anesthesia↗

PubMed2000

Involvement of minor structural proteins in recombination of polyoma virus DNA.

We have previously observed that a polyoma-mouse chimeric DNA molecule (RmI) in which the murine DNA insert is flanked by directly repeated viral sequences is effectively converted into unit-length polyoma DNA upon transfection of permissive mouse cells. This intramolecular recombination event appears to be dependent on VmP1, a protein encoded by RmI which includes the 328 N-terminal amino acids of polyoma VP1, and nine amino acids of murine origin carrying the C-terminus of the protein. We report here that introducing mutations into the VP2/VP3 coding sequence reduces the ability of RmI to generate polyoma DNA, even though the same mutations seem to exert little or no effect on the ability of polyoma DNA to either replicate or accumulate inside transfected cells. A mutation affecting VP2 alone being as effective as one that affects both VP2 and VP3, VP2 appears to be playing a critical role in recombination.

Animals↗

PubMed1997

p53-mediated DNA renaturation can mimic strand exchange.

The process of strand exchange is considered to be the hallmark of DNA recombination. Proteins known to carry out such exchange are believed to operate via one or the other of two mechanisms. RecA-like proteins promote the formation of a three-stranded or triplex synaptic intermediate in which strand exchange occurs, whereas other proteins would allow the coordinated exonucleolytic degradation of one strand in the duplex DNA and its replacement by an invading strand of similar sequence and polarity. In view of properties ascribed to it, we have attempted to determine whether p53 belongs to one or the other of these groups of proteins. The in vitro assay used relies on a double-stranded (ds) oligonucleotide (oligo 1+2) and a single-stranded (ss) oligonucleotide (oligo 3), part of which is complementary to oligo 1. The data collected suggest that, under the conditions of the assay, oligo 1+2 undergoes partial denaturation; p53 then catalyzes renaturation of oligo 1 with oligo 3, rather than true strand exchange. Since p53 is not known for being able to 'melt' DNA, it would seem unlikely that this protein would effect strand exchange in vivo without assistance from another, denaturing, protein.

Animals↗

PubMed1996

An enhancer of recombination in polyomavirus DNA.

Previous work from this laboratory has indicated that intramolecular homologous recombination of polyomavirus (Py) DNA is dependent upon promoter structure or function. In this report, we demonstrate that Py DNA contains not two but three binding sites for transcription factor YY1, all located on the late side of viral origin of replication (ori) and the third well within the VP1 coding sequence. This third site (Y3), which may or may not play a role in transcription regulation, is immediately adjacent to a previously described recombination hot spot (S1/S2). We found that Py replicons carrying an altered Y3 site recombined in a manner suggesting partial inactivation of the S1/S hot spot. Point mutations precluding the binding of YY1 to Y3 in vitro depressed hot spot activity in vivo; however, of the two reciprocal products reflecting recombination at this spot, only that carrying the mutated Y3 site arose at a reduced rate. These results are interpreted in light of a model assuming that recombination occurs within a transcriptionally active viral chromatin tethered to the nuclear matrix by YY1.

Animals↗

PubMed1995

A hotspot for promoter-dependent recombination in polyomavirus DNA.

We have engineered polyomavirus (Py) DNA molecules carrying two large direct repeats within the late coding region, as well as a deletion encompassing the TATA box in the early promoter. Such constructs recombine less readily than a construct containing the same duplication of late sequences, but an intact early promoter. Furthermore, residual recombination in the molecules with a deletion occurs between homologous sites which differ from those used in the molecule without deletion. These findings are consistent with recombination being stimulated by transcription originating from the early promoter, rather than facilitated by the "openness" of viral chromatin undergoing transcription.

Animals↗

PubMed1995

Variation outside variable segments of the major outer membrane protein distinguishes trachoma from urogenital isolates of the same serovar of Chlamydia trachomatis.

OBJECTIVES--Whereas serovars A, B, Ba and C of Chlamydia trachomatis are usually associated with trachoma, two of these serovars (Ba and C) are occasionally observed in urogenital infections. Variation in the gene encoding the major outer membrane protein (MOMP) was explored to distinguish urogenital from trachoma specimens of the same serovar. METHODS--A large portion of the MOMP gene was amplified by nested PCR directly from clinical samples from trachoma or urogenital infection and the serovar of the infecting C trachomatis was determined by restriction fragment length polymorphism (RFLP). Amplified DNA from trachoma serovars B, Ba and C and from urogenital serovars Ba, C, D and E was sequenced by the dideoxy chain termination method. RESULTS--While almost identical in variable segment (VS)I, three urogenital Ba samples differed from all trachoma B and Ba samples at eight nucleotides including two sites which changed amino acids in the constant region upstream of VSI. An identical sequence in this region was observed for the reference urogenital D serovar. Variation in this same region upstream of VSI also distinguished 40% of serovar D samples from prototype D including three that were sequenced. Two urogenital C differed from trachoma C samples at four sites that changed the MOMP amino acid sequence including two changes in the constant region between VSII and III and single changes in VSII and III. On the basis of these sequence determinations, RFLP was predicted which allowed extension of these observations to 20 other urogenital Ba, 12 trachoma B or Ba, seven variant D, 12 D, four urogenital C and three trachoma C samples without further sequencing. CONCLUSION--Urogenital Ba and C samples have VSI or II and III sequences identical or very similar to trachoma strains of the same serovar, but resemble more closely other serovars in the constant regions. Urogenital serovar D samples can also be divided into two genotypes on the basis of sequence differences in the constant region preceding VSI.

Amino Acid Sequence↗

PubMed1994

The tapestry of care.

The analogy of a tapestry is used to explore artistic nursing activities. The warp is composed of acontextual knowledge and skills, available resources, and agency policies. The weft is the creative pattern of care. A sensitive awareness of the total context of the person being cared for enables the nurse to creatively use approaches and activities that match and balance the person's values, needs, and interests. An example of how the weft was developed for one client is described.

Adult↗

PubMed1993

Stimulation frequency-dependent neuromuscular junction transmission defects in patients with prior poliomyelitis.

Generalized fatigue and muscle fatiguability are major symptoms of post-poliomyelitis syndrome (PPS), and may be due to neuromuscular junction transmission defects, as suggested by increased jitter on single fiber electromyography (SFEMG). To determine the etiology of this defect, we studied jitter at low (1, 5 Hz) and high (10, 15, 20 Hz) frequency stimulation with stimulation SFEMG in 17 post-polio patients with muscle fatiguability, and in 9 normal controls. In 5 of 17 PPS patients and in 1 of 9 controls, jitter was significantly higher (unpaired t-test, P < 0.05) at high frequency stimulation (HFS). In the remaining PPS patients and controls there was no significant difference in jitter at high and low stimulation frequencies. PPS patients with increased jitter at HFS had a significantly longer time interval since acute polio (mean 48.5 years) than PPS patients without increased jitter at HFS (mean 40 years; P < 0.05), but were not distinguished by other historical or clinical criteria. We conclude that the neuromuscular junction defect in post-polio patients is similar to that observed in amyotrophic lateral sclerosis, and is probably due to ineffective conduction along immature nerve sprouts and exhaustion of acetylcholine stores. The appearance of an increase in jitter with HFS in post-polio patients may be dependent upon time after acute polio.

Adult↗

PubMed1993

Anticholinesterase-responsive neuromuscular junction transmission defects in post-poliomyelitis fatigue.

Disabling generalized fatigue and muscle fatiguability are common features of post-poliomyelitis syndrome (PPS). In 17 fatigued PPS patients, we measured jitter on stimulation single-fiber electromyography (S-SFEMG) for at least 3.5 min before and after i.v. injection of 10 mg edrophonium. We observed reduction in jitter (defined as a significant difference in jitter means before and after edrophonium, unpaired t-test P < 0.05) in 7 patients, no change in 8, and a significant increase in 2 patients. Blinded to their edrophonium results, the 17 patients were treated with pyridostigmine 180 mg/day for 1 month, with a subjective improvement of fatigue in 9 patients, and with a significant reduction in mean Hare fatigue scores in the entire group of 17 patients (pre = 2.71, and post = 1.71; Wilcoxan signed rank sum test, P < 0.05). Edrophonium-induced reduction of jitter on S-SFEMG was significantly associated with pyridostigmine-induced subjective improvement of fatigue (Fisher's exact test, P < 0.04). A significant reduction in fatigue with pyridostigmine was observed only in the 7 patients who experienced a significant reduction in jitter with edrophonium (Wilcoxan signed rank sum test, P = 0.03). In addition, the 9 pyridostigmine responders experienced a significant reduction in jitter means pre- and post-edrophonium (100% vs. 88%, Bonferroni corrected, P < 0.01). We conclude that neuromuscular transmission as measured by jitter on S-SFEMG can improve with edrophonium in a proportion of PPS patients, and that generalized fatigue and muscle fatiguability in some patients with PPS may be due to anticholinesterase-responsive NMJ transmission defects.

Adult↗

PubMed1991

Electrophysiology and electrodiagnosis of the post-polio motor unit.

Post-poliomyelitis syndrome refers to new symptoms that may occur years after recovery from poliomyelitis. The most common of these symptoms are new weakness, fatigue, and pain. This article describes electrodiagnostic studies--conventional electromyography (EMG), single fiber electromyography (SFEMG), and macroelectromyography (macro-EMG)--that have provided information on the post-polio motor unit and on the possible etiology of some post-polio syndrome symptoms. Muscular fatigue, and indirectly, general fatigue, may be due to neuromuscular junction transmission defects in some post-polio individuals, as suggested by reduction of the compound motor action potentials on repetitive stimulation, and increased jitter and blocking on SFEMG. Progressive weakness and atrophy in post-polio syndrome is probably due to a distal degeneration of post-polio motor units with resultant irreversible muscle fiber denervation. Electrodiagnostic evidence of ongoing denervation includes fibrillation and fasciculation potentials on conventional EMG, increased jitter and blocking on SFEMG, and smaller macro-EMG amplitudes in newly weakened post-polio muscles. However, even though electrodiagnostic studies have provided insight into the possible causes of some post-polio syndrome symptoms, no specific electrodiagnostic test for the syndrome is currently available.

Action Potentials↗

PubMed1990

Neurologic sequelae of domoic acid intoxication due to the ingestion of contaminated mussels.

In late 1987 there was an outbreak in Canada of gastrointestinal and neurologic symptoms after the consumption of mussels found to be contaminated with domoic acid, which is structurally related to the excitatory neurotransmitter glutamate. We studied the neurologic manifestations in 14 of the more severely affected patients and assessed the neuropathological findings in 4 others who died within four months of ingesting the mussels. In the acute phase of mussel-induced intoxication, the patients had headache, seizures, hemiparesis, ophthalmoplegia, and abnormalities of arousal ranging from agitation to coma. On neuropsychological testing several months later, 12 of the patients had severe anterograde-memory deficits, with relative preservation of other cognitive functions. Eleven patients had clinical and electromyographic evidence of pure motor or sensorimotor neuronopathy or axonopathy. Positron-emission tomography of four patients showed decreased glucose metabolism in the medial temporal lobes. Neuropathological studies in the four patients who died after mussel-induced intoxication demonstrated neuronal necrosis and loss, predominantly in the hippocampus and amygdala, in a pattern similar to that observed experimentally in animals after the administration of kainic acid, which is also structurally similar to glutamate and domoic acid. We conclude that intoxication with domoic acid causes a novel and distinct clinicopathologic syndrome characterized initially by widespread neurologic dysfunction and then by chronic residual memory deficits and motor neuronopathy or axonopathy.

Animals↗

PubMed1990

Gluteal nerve damage following total hip arthroplasty. A prospective analysis.

Injuries to the peroneal or tobial divisions of the sciatic nerve occur in approximately 0.7-7.6% of patients undergoing total hip arthroplasty. No prior studies have investigated the incidence of injury to the superior or inferior gluteal nerves during hip surgery. This study evaluates the incidence of injury to the superior and inferior gluteal nerves in 55 patients undergoing total hip arthroplasty using a newly devised EMG scoring system. Subclinical gluteal nerve injury was documented in over 77% of patients, whether a posterior or a lateral approach to the hip was used.

Adult↗

PubMed1990

Alternative homologous and nonhomologous products arising from intramolecular recombination.

RmI, a chimeric DNA molecule containing polyomavirus (Py) and mouse sequences, generates unit-length Py DNA via intramolecular recombination between two directly repeated viral sequences of 182 base pairs (S repeats). To analyze the contribution of the S repeats in this process, we produced mutants of RmI carrying deletions in either one or both S repeats and tested them for their ability to recombine in mouse 3T6 cells. Mutant DNAs were found to yield unit-length Py DNA as long as they carried a minimal internal homology of 40 to 50 base pairs. Unlike RmI itself, however, the mutants also gave rise to nonhomologous recombination products. These results suggest that when the generation of homologous products is hampered by a limiting homology, nonhomologous products may arise instead of homologous ones. Therefore, the initial step(s) in the mechanisms yielding the two kinds of products could be identical.

Animals↗