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Biomedical subjects

M Sanders

Publications and source records attributed to M Sanders.

At least 37 records · Page 2Linked to original sources
PubMed1996

Influence of training dose on nicotine discrimination in humans.

Non-human research indicates that drug discrimination results may depend largely on the specific training conditions, including initial training dose. It has recently been shown that humans can discriminate among different doses of nicotine delivered by nasal spray. In this study, we examined the influence of training dose on subsequent behavioral discrimination of a range of nicotine doses. Male (n = 17) and female smokers (n = 16) were randomly assigned to "low" (10 micrograms/kg) versus "high" (30 micrograms/kg) nicotine training dose groups and trained reliably to discriminate this dose from placebo (0) on day 1 (> or = 80% correct identification). All but six subjects (four in low, two in high) learned this discrimination and continued on to day 2, in which both groups received 0, 5, 10, 20, and 30 micrograms/kg in ascending order (30 min between dosings) and were tested for generalization with their training dose using quantal and quantitative behavioral discrimination tasks. Subjective responses via traditional self-report measures were also assessed. Nicotine-appropriate responding on day 2 was significantly greater in low- versus high-dose groups, especially at 5 micrograms/kg. However, this difference due to training dose was seen more in women than in men. Discrimination behavior was associated with subjective effects of head rush in males, and with head rush and decline in urge to smoke in females. These results show that discriminative stimulus effects of nicotine are not fixed properties of the drug, but can be influenced by training conditions, and that effects associated with this discrimination may differ between men and women.

Adult↗
PubMed1996

MRI of the optic nerve in benign intracranial hypertension.

We investigated the MRI appearance of the optic nerve and its cerebrospinal-fluid-containing sheath in 17 patients with benign intracranial hypertension (BIH) and 15 normal controls. Using phased-array local coils, 3-mm coronal T2-weighted fat-suppressed fast spin-echo images were obtained with an in-plane resolution of < 0.39 mm. The optic nerve and its sheath were clearly differentiated. An enlarged, elongated subarachnoid space around the optic nerve was demonstrated in patients with BIH. High-resolution MRI of the optic nerve offers additional information which may be of value for diagnosis and in planning and monitoring treatment.

Adolescent↗
PubMed1996

Placental basal plate myometrial fibers: clinical correlations of abnormally deep trophoblast invasion.

OBJECTIVE: To assess the incidence of placental basal plate myometrial fibers in preterm and term gestations and correlate this finding with clinical observations and placental histopathology. METHODS: Placentas from 457 singleton births before 32 weeks' gestation and 108 uncomplicated singleton births after 37 weeks' gestation were examined histopathologically. Pregnancies complicated by maternal chronic hypertension, diabetes mellitus, coagulopathy, placenta previa, stillbirth, multiple fetuses, and fetal congenital anomalies were excluded from both groups. In the preterm group, 158 patients had preterm labor with intact membranes, 192 had preterm premature rupture of membranes (PROM), 31 had placental abruption without hypertension, and 76 had preeclampsia. Histopathology detected the presence of placental basal plate myometrial fibers, placental vascular lesions, and villous damage related to vascular insufficiency. RESULTS: Forty-four of 457 (9.6%) of preterm placentas had basal plate myometrial fibers, compared with one of 108 (0.9%) term controls (P < .001). Uteroplacental vessels with abnormal physiologic changes were more frequent and placental weights were lower in cases with basal plate myometrial fibers (P < .003 and P < .03, respectively). No other uteroplacental vascular lesions were related to basal plate myometrial fibers. The frequency of placental basal plate myometrial fibers was nine of 76 (12%) in cases complicated by preeclampsia, 21 of 192 (11%) cases of PROM, nine of 158 (5.7%) cases of preterm labor, and four of 31 (13%) cases of placental abruption without hypertension; these frequencies were not significantly different, and there was no significant relationship to gravidity, parity, mode of delivery, or birth weight. CONCLUSION: Placental basal plate myometrial fibers occur in ten times as many preterm births as term births. This finding is associated with both abnormal uteroplacental physiologic changes and decreased placental weight, and may explain the increased incidence of abnormalities of the third stage of labor associated with preterm delivery.

Female↗
PubMed1996

Biochemical and molecular characterization of acetylcholinesterase from the hagfish Myxine glutinosa.

To obtain information about the evolution of the cholinesterases, we investigated the cholinesterase activity of an agnathan vertebrate, the hagfish Myxine glutinosa. On the basis of evidence from enzymology, pharmacology, and molecular biology, we conclude that the cholinesterase activity is due to acetylcholinesterase (AChE). The enzyme hydrolyzes acetylthiocholine preferentially and exhibits substrate inhibition. The hydrolysis of both acetylthiocholine and butyrylthiocholine are inhibited in parallel by cholinesterase inhibitors, with the AChE-specific drug BW284c51 being the most potent; however, this drug and propidium, a peripheral anionic site ligand, are much weaker inhibitors of the hagfish enzyme than of Torpedo AChE. We used sequential extraction, collagenase digestion, and velocity sedimentation on sucrose gradients to determine that the AChE from the skeletal muscle of the hagfish is present in both globular and asymmetric forms. We also used the polymerase chain reaction with degenerate oligonucleotide probes and genomic DNA to obtain a 1 kb gene fragment for hagfish AChE. The enzyme has an acyl binding site typical of other vertebrate AChE, but lacks two aromatic residues implicated in the function of the peripheral anionic subsite. We discuss the relevance of our findings to the evolution of the cholinesterases in the vertebrates.

Acetylcholinesterase↗
PubMed1996

A randomised prospective study of outpatient haemodilution for central retinal vein obstruction.

PURPOSE: Central retinal vein obstruction (CRVO) has significant visual morbidity. We prospectively evaluated an outpatient haemodilution (HD) regimen for CRVO. METHODS: We recruited 59 patients with CRVO of less than three months' duration and visual acuity (VA) worse than or equal to 6/9.5. Thirty patients underwent HD (packed cell volume of <0.35, 12 weeks); there were 29 controls and follow-up was for six months. RESULTS: Incidence rates for VA improvement (P = 0.708) and rubeosis iridis (P = 0.619) between the two groups were not different. The incidence rate of VA deterioration was 5.315 times higher with HD (P = 0.035, Cox Proportional analysis). CONCLUSION: This data does not support the previous studies on haemodilution.

Adult↗
PubMed1996

Radiosurgical management of meningiomas.

The management of residual, recurrent, or small skull base meningiomas is controversial. Stereotactic radiosurgery has emerged as an alternative treatment. We report our experience from September 1991 to August 1994 of treatment of 20 such patients [18 females -age 19-82 years, followed for 6-36 months (mean 15.5 months)] with the Leksell Gamma Knife. Nine patients were treated either with recurrent (2 patients-2 operations each) or residual tumor. Twelve patients had skull base, 3 optic nerve, 3 parasagittal, and 1 residual torcular tumor. Mean volume/diameter was 9.172 mm3/25 mm.

Adult↗
PubMed1996

Healthcare combinations. Part III: Cultural success through organizational involvement. Interview by Terry G. Williams.

Throughout the integration process, organizations must constantly envision new opportunities, create mechanisms for communication, set goals and build accountabilities at appropriate levels within the organization. Ideally, an integration process will identify and build cultural strengths wherever they are in the organization and minimize the negative impact of change. An integration process that taps the creative, productive potential throughout the organization will not only reap more benefit from the integration process itself, but also will successfully navigate the culture through the rough waters of change.

Decision Making, Organizational↗
PubMed1995

Distribution of polycyclic aromatic hydrocarbons in oyster (Crassostrea virginica) and surface sediment from two estuaries in South Carolina.

The concentration of polycyclic aromatic hydrocarbons (PAHs) was determined in oysters and sediments collected from two high salinity estuaries from the coast of South Carolina. The two estuaries were Murrells Inlet (urban), an estuary receiving urbanized drainage and run-off, and North Inlet (non-urban), receiving drainage from heavily forested terrain and minimal anthropogenic input. A minimum of thirty (30 stations were sampled in Murrells and North Inlets, respectively. A composite oyster sample (n = 30) was analyzed for each station. For sediment, a sample from the top 3-5 cm of the sediment surface from each station was analyzed. In oyster from Murrells Inlet, total PAHs concentrations within the 75 percentile were located in the northern portion of the estuary near marinas, adjacent to residential areas of high population density, near commercial enterprises or run-off from storm drains. Total PAHs within the 25 percentile were located near the mouth of the estuary. These results showed PAHs concentration gradient in the estuary that was highest in narrow creeks, where the urban shore interfaced with tidal creeks and lowest at the mouth of the estuary. In the case for sediment, a similar gradient was observed. In comparing the mean total PAHs of the two inlets, Murrells Inlet had significantly higher (p < 0.01) total PAHs concentrations than North Inlet for oyster and sediment, respectively. In comparing PAHs concentrations among the two matrices in Murrells Inlet, these data showed that the pattern of individual PAHs in oyster and in sediment were different. Oysters tended to accumulate the lower molecular weight and the more water-soluble PAHs compared to PAHs found in sediment. As expected, differences in octanol/water partition coefficient among individual PAHs and the greater persistence of the higher molecular weight PAHs contributed to the accumulation patterns in oyster and sediment.

Animals↗
PubMed1995

Sequence and domain organization of scruin, an actin-cross-linking protein in the acrosomal process of Limulus sperm.

The acrosomal process of Limulus sperm is an 80-microns long finger of membrane supported by a crystalline bundle of actin filaments. The filaments in this bundle are crosslinked by a 102-kD protein, scruin present in a 1:1 molar ratio with actin. Recent image reconstruction of scruin decorated actin filaments at 13-A resolution shows that scruin is organized into two equally sized domains bound to separate actin subunits in the same filament. We have cloned and sequenced the gene for scruin from a Limulus testes cDNA library. The deduced amino acid sequence of scruin reflects the domain organization of scruin: it consists of a tandem pair of homologous domains joined by a linker region. The domain organization of scruin is confirmed by limited proteolysis of the purified acrosomal process. Three different proteases cleave the native protein in a 5-kD Protease-sensitive region in the middle of the molecule to generate an NH2-terminal 47-kD and a COOH-terminal 56-kD protease-resistant domains. Although the protein sequence of scruin has no homology to any known actin-binding protein, it has similarities to several proteins, including four open reading frames of unknown function in poxviruses, as well as kelch, a Drosophila protein localized to actin-rich ring canals. All proteins that show homologies to scruin are characterized by the presence of an approximately 50-amino acid residue motif that is repeated between two and seven times. Crystallographic studies reveal this motif represents a four beta-stranded fold that is characteristic of the "superbarrel" structural fold found in the sialidase family of proteins. These results suggest that the two domains of scruin seen in EM reconstructions are superbarrel folds, and they present the possibility that other members of this family may also bind actin.

Acrosome↗
PubMed1995

High resolution magnetic resonance imaging of the anterior visual pathway in patients with optic neuropathies using fast spin echo and phased array local coils.

High resolution MRI of the anterior visual pathways was evaluated using frequency selective fat suppressed fast spin echo (FSE) sequences in conjunction with phased array local coils in patients with optic neuropathies. Fifteen normal controls and 57 patients were examined. Coronal T2 weighted fat suppressed FSE images were obtained in 11 minutes with an in plane resolution of 0.39 x 0.39 mm. The optic nerve and its sheath containing CSF were clearly differentiated. Central retinal vessels were often visible. In demyelinating optic neuritis and in anterior ischaemic optic neuropathy high signal within the nerve was readily delineated. Meningiomas and gliomas involving the optic nerve were precisely visualised both in the orbit and intracranially. Extrinsic compression of the optic nerves was readily visualised in carotid artery ectasia and dysthyroid eye disease. Enlarged subarachnoid spaces around the optic nerves were demonstrated in benign intracranial hypertension. High resolution MRI of the anterior visual pathway represents an advance in the diagnosis and management of patients presenting with optic neuropathy.

Adult↗
PubMed1995

Safety of unilateral and bilateral percutaneous cervical cordotomy in 80 terminally ill cancer patients.

PURPOSE AND METHODS: The safety of percutaneous cervical cordotomy (PCC) and bilateral percutaneous cervical cordotomy (BPCC) was studied in 62 and 18 patients, respectively, with intractable malignant pain. Cordotomy was indicated for pain that did not respond to any other therapy. RESULTS: After PCC, 54 patients showed satisfactory, six partial, and two no pain relief. Concerning major permanent complications, urinary retention, hemiparesis, and mirror-image pain occurred in four (6.5%), five (8.1%), and four (6.5%) patients, respectively. After BPCC, nine patients showed satisfactory, six partial, and three no pain relief. The major permanent complications were the same as after PCC, and occurred in two (11.1%), two (11.1%), and one (5.6%) patient, respectively. Sleep-induced apnea was not observed in any patient. CONCLUSION: In the treatment of intractable malignant pain, localized unilaterally, if other symptomatic management fails, PCC is a recommendable procedure, particularly when pain due to movement dominates. However, due to the high incidence of complications combined with the high failure rate, BPCC is not recommended.

Adult↗
PubMed1995

beta-Scruin, a homologue of the actin crosslinking protein scruin, is localized to the acrosomal vesicle of Limulus sperm.

Scruin (alpha-scruin) is an actin bundling protein found in the acrosomal process of Limulus polyhemus sperm. We have cloned and sequenced a second scruin isoform from Limulus, beta-scruin, that is 67% identical to alpha-scruin. Northern and Southern analyses confirm that beta-scruin and alpha-scruin are encoded by distinct genes. The sequence of beta-scruin, like alpha-scruin, is organized into N- and C-terminal superbarrel domains that are characterized by a six-fold repeat of a 50 residue motif. Western analysis using rabbit polyclonal antisera specific for alpha- and beta-scruin indicate that beta-scruin, like alpha-scruin, is found in Limulus sperm but not blood or muscle. Both immunofluorescence microscopy and immunogold-EM localize beta-scruin within the acrosomal vesicle at the anterior of sperm but not in the acrosomal process. The function of beta-scruin in this membrane-bounded compartment that is devoid of actin is unknown. However, the location of beta-scruin together with the fact that it contains two putative beta-superbarrel structural folds, which are known to be catalytic domains in a number of proteins, suggests it may have a possible enzymatic role.

Acrosome↗
PubMed1994

Molecular and cellular concepts in atherosclerosis.

Atherosclerosis is a complex disease of uncertain cause. Its pathobiology is believed to represent an abnormal expression of the processes of vascular healing. Etiologic models derive from a 'response to injury' paradigm and can be divided into three separate disease stages: endothelial dysfunction, smooth muscle proliferation and architectural disruption. The initiating event of endothelial dysfunction is unknown, but is believed to be related to low-density lipoproteins and/or their oxidized derivatives. Endothelial injury is signalled to the smooth muscle cells of the media by three routes: direct cell-cell interaction, secretion of soluble growth factors and monocyte-derived cytokines. Monocytes are recruited by the endothelium and invade the subintimal space by a complex interaction of a variety of adhesion proteins and receptors on both cell types. Smooth muscle cell proliferation is initiated by a change in phenotype expression from 'contractile' to 'synthetic' resulting from the binding of fibronectin to specific integrin receptors. Three functionally distinct activities may represent separate subtypes of the 'synthetic phenotype': migration from the media to the intima, increased proliferation and inappropriate extracellular matrix synthesis. The loss of normal regulatory control and anchorage independence of proliferation suggest a relationship to oncogenic transformation. Both migration and proliferation result from the binding of platelet-derived growth factor-like factors to smooth muscle cell receptors, which initiates a cascade of intracellular molecular events leading either to cytoskeletal locomotory restructuring or cell cycle activation. Both pathways also appear to be coregulated by integrin receptors and both depend upon phosphorylation of cell membrane, cytosolic and nuclear regulatory proteins. Clinical expression of atherosclerosis may follow sudden loss of architectural integrity of the intimal plaque by three different mechanisms: plaque fissuring, intraluminal plaque rupture or intramural hemorrhage related to abnormal vessel wall stress and/or biochemistry.

Animals↗
PubMed1994

Portable recording in the assessment of obstructive sleep apnea. ASDA standards of practice.

The objective assessment of patients with a presumptive diagnosis of obstructive sleep apnea (OSA) has primarily used attended polysomnographic study. Recent technologic advances and issues of availability, convenience and cost have led to a rapid increase in the use of portable recording devices. However, limited scientific information has been published regarding the evaluation of the efficacy, accuracy, validity, utility, cost effectiveness and limitations of this portable equipment. Attaining a clear assessment of the role of portable devices is complicated by the multiplicity of recording systems and the variability of clinical settings in which they have been analyzed. This paper reviews the current knowledge base regarding portable recording in the assessment of OSA, including technical considerations, validation studies, potential advantages and disadvantages, issues of safety, current clinical usage and areas most in need of further study.

Ambulatory Care↗