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Biomedical subjects

S Levin

Publications and source records attributed to S Levin.

At least 127 records · Page 7Linked to original sources

Levels of pyrimethamine in sera and cerebrospinal and ventricular fluids from infants treated for congenital toxoplasmosis. Toxoplasmosis Study Group.

Pyrimethamine levels in sera, cerebrospinal fluid (CSF), and ventricular fluid were measured by using reversed-phase high-pressure liquid chromatography. The specimens were from 37 infants receiving pyrimethamine for treatment of suspect or proven congenital toxoplasmosis. Pyrimethamine half-life in serum was 64 +/- 12 h when determined by study of terminal-phase kinetics of samples obtained from nine babies. This half-life was significantly different (P = 0.008) from the pyrimethamine half-life (33 +/- 12 h) determined by terminal-phase kinetics for two babies of the same age taking phenobarbital. Serum pyrimethamine levels at various intervals after dosages of pyrimethamine were also lower for infants receiving phenobarbital. Levels measured in sera from babies taking the same dose of pyrimethamine throughout their first year of life did not appear to vary significantly over time or at different ages (P greater than 0.05). Mean +/- standard deviation serum levels 4 h after a pyrimethamine dose were 1.297 +/- 0.54 micrograms/ml for babies taking 1 mg of pyrimethamine per kg of body weight daily and 0.7 +/- 0.26 microgram/ml for babies taking 1 mg/kg each Monday, Wednesday, and Friday. Levels in CSF were approximately 10 to 25% of concomitant levels in serum. Serum folate levels for infants who took 0.64 to 1.7 mg leukovorin per kg ranged from 33 to 663 ng/ml. To determine whether the levels of pyrimethamine in serum and CSF of treated infants were in a range that affected the most virulent, rapidly replicating, and standard laboratory strain of Toxoplasma gondii, effects of various concentrations of pyrimethamine and sulfadiazine on replication of T. gondii in vitro were assessed. The levels of the antimicrobial agents effective in vitro were in the range of levels of pyrimethamine achieved in sera and CSF. Although folinic acid could inhibit the therapeutic effect of pyrimethamine and sulfadiazine in vitro, inhibition was noted only at levels (> or = 4,800 ng/ml) that were considerably higher than the folate levels found in the treated infants' sera.

Chromatography, High Pressure Liquid↗

Plasma and tissue hormones in the dog after administration of the prostaglandin analogue, misoprostol.

Dogs were given a prostaglandin analogue, misoprostol, at a dose that significantly increases gastrointestinal epithelial cell proliferation. Both basal and postprandial concentrations of gastrin were significantly higher in the misoprostol-treated dogs and more than doubled after the meal in both the controls and in the test group. Plasma enteroglucagon, cholecystokinin, insulin and glucose-dependent insulinotrophic peptide all increased postprandially, with no effect of misoprostol. Tissue concentrations of bombesin, gastrin and somatostatin were unaffected by misoprostol, but the fundic glucagon-like immunoreactivity was significantly increased. Thus high doses of misoprostol have only minor effects on gastrointestinal regulatory peptides, suggesting that the trophic effect of prostaglandins on the intestinal tract may be direct.

Animals↗

Glycemic control and complications in type II diabetes. Design of a feasibility trial. VA CS Group (CSDM)

OBJECTIVE: To determine, after 1 yr of follow-up in type II diabetes patients, whether a statistically and clinically significant difference can be achieved in HbA1c between a standard therapy group and an intensively treated group, while maintaining HbA1c levels in both groups within ranges acceptable in regular community practice. Secondary objectives include assessment of patient adherence to protocol, side effects, and accuracy of data collection. RESEARCH DESIGN AND METHODS: This is a prospective, randomized, controlled VA CS conducted with 151 patients at five VAMCs. Patients are males, age 40-69 yr, treated at entry with a maximum dose of sulfonylurea or with insulin, exhibiting an HbA1c level > 3 SDs above the normal mean (5.05 + 3 x 0.50 = > 6.55%). Standard control is achieved with insulin and intensive control with a step-up regimen including insulin alone or insulin/glipizide combinations. Education and management of cardiovascular risk factors are handled similarly in both groups. Primary macrovascular end points are nonfatal myocardial infarction, congestive heart failure, stroke, amputation, and cardiovascular death. Primary microvascular end points are appearance and progression of retinopathy, documented by centrally read seven-field-stereo fundus photographs. Other measured indicators include resting and ambulatory ECGs, ventricular function (MUGA scan), serum lipid and apolipoprotein levels, plasma fibrinogen, nonsymptomatic peripheral vasculopathy, neuroautonomic status by heart-beat variation on Valsalva maneuver, and microalbuminuria. CONCLUSIONS: This study may be the basis for a long-term trial, involving 1400 patients, to assess the long-term effects of metabolic control on macro- and microvascular end points.

Adult↗

Coping with infertility: a new nursing perspective.

Infertility is a major life stressor, and reproductive failure is difficult to accept. Many couples become trapped in a cycle of repeated medical treatment, repeating painful patterns without developing insight or growth, feeling powerless to achieve their goal or move on. The causes of inappropriate coping behaviors are not well understood, and there is little direction for the nurse clinician's efforts to assist the couple with decision making. The use of superstition and ritual (magical thinking or magical ideation) by couples with infertility is discussed, and its role as a potential barrier to resolution is evaluated. A clinical tool for assessing the extent of magical ideation is described and its potential clinical utility explored. Women who have experienced a previous pregnancy may be more likely than nulliparas to substitute magical thinking for coping behaviors that might bring them closer to resolution. Problems with current research in this area are discussed, and directions for developing clinical nursing interventions are suggested.

Adaptation, Psychological↗

Rembrandt toothpaste stain prevention with and without the use of Peridex.

Sixty-five subjects were assigned to use Crest or Rembrandt dentifrice with either a placebo or Peridex rinse for eight weeks. One group, using Peridex, started with Crest and switched to Rembrandt at week four of the study. There were no significant differences among the groups on gingivitis, plaque, or calculus by the conclusion of the study. On the stain intensity index there was a significant statistical difference on buccal surfaces between Crest and Rembrandt with placebo compared to Crest with Peridex. On lingual surfaces, Rembrandt with placebo rinse was significantly lower than all Peridex rinse groups by the end of the study. From baseline to the conclusion of the study, Crest with placebo had no change in stain intensity, while Rembrandt with placebo had a significant drop on both buccal and lingual surfaces. The Peridex groups had increases on buccal stain intensity. On stain area scores, by the conclusion of the study both Crest and Rembrandt with placebo were significantly different from Crest with Peridex on buccal and lingual surfaces. Over time there was no significant change in stain area for the Crest with placebo groups. Rembrandt and placebo was significantly lower on stain area from baseline to week eight on buccal surfaces. The Peridex groups had increases in stain area over the study period.

Adolescent↗

Fast cell membrane displacements in B lymphocytes. Modulation by dihydrocytochalasin B and colchicine.

A novel type of cell membrane movement was characterized in B lymphocytes. Local submicron cell membrane displacements, within the frequency range 0.3-15 Hz, were registered in a murine lymphoma B cell line by a novel optical method based on point dark field microscopy. The cell membrane displacements were measured by monitoring changes in light scattering from very small illuminated areas (0.25 microns2) at the edge of the cell surface. B lymphocytes manifest a relative change in light scattering of 7.7 +/- 1.3% (mean +/- SD) which corresponds to cell membrane transverse displacement of 131 +/- 22 nm. The confinement of cell membrane displacements to microdomains (less than or equal to 0.2 microns2) emerged from the observed dependence of the displacement amplitude on the area size from which it is monitored. Colchicine (1 microM) decreased membrane fluctuations down to a value of 88 +/- 14 nm, whereas dihydrocytochalasin B (2 microM) increased the amplitude of membrane displacements up to 184 +/- 31 nm. These findings demonstrate the existence of a dynamic mechanical interaction between the cytoskeleton and the cell membrane in the frequency range of 0.3-15 Hz. The modulation of these interactions by the disruption of microfilaments or or microtubules is explained in terms of the induced strain changes imposed on the cell membrane.

Animals↗

Field flow fractionation in biomedical analysis.

Samples of biomedical interest which have been analysed by field-flow fractionation techniques are surveyed. The list begins with whole cells and microorganisms, going through viruses, nucleic acids, cell fragments and organelles, down to proteins and their aggregates. The principles of separation in the normal and steric mode of retention are illustrated, and instrumentation and techniques are described. The review concentrates mainly on the two systems of choice for biomedical applications: sedimentation and flow field-flow fractionation.

Cell Fractionation↗

Continuous separation of particles from macromolecules in split-flow thin (SPLITT) cells.

A split-flow thin (SPLITT) cell with a perpendicular driving force of one gravity has been utilized for the rapid separation of micron-sized particles from macromolecules. The procedure involves the simultaneous use of two transport mechanisms and thus two operating modes: a sedimentation process controls the displacement of the particles across the thickness of the thin channel, while diffusion controls the displacement of macromolecules. The theoretical equations for these two operating modes are summarized and it is shown how the two modes can be combined to yield specified recovery factors. The theory was tested on a mixture of 10 microns polystyrene latex beads and three different proteins. The observed separation was in excellent agreement with theory. Attempts to fractionate red blood cells and plasma proteins from whole blood were only partially successful as a consequence of the weak sedimentation of red blood cells. Various remedies to this problem are suggested, the most promising of which is the use of a SPLITT cell subject to mild centrifugal forces.

Cell Fractionation↗

6-trans-leukotriene B4 is a neutrophil chemotaxin in the guinea pig dermis.

The products of the 5- and 12-lipoxygenase (5-LO, 12-LO) pathways of arachidonic acid metabolism are implicated as proinflammatory mediators in a number of disease states. 12(R)-hydroxyeicosatetraenoic acid [12(R)-HETE] is present in large quantities in human psoriatic lesional skin and can be further metabolized by 5-LO to 5(S), 12(R)-dihydroxy-(6E,8Z,10E,14Z)-eicosatetraenoic acid (6-trans-LTB4). Furthermore, leukotriene B4 (LTB4) and the sulfidopeptide leukotrienes (LTC4, LTD4) can be transformed to 6-trans-LTB4. When injected into the guinea pig dermis, 6-trans-LTB4 (1.0, 10.0, 20.0 micrograms/intradermal site) caused a significant (P less than 0.02) infiltration of polymorphonuclear leukocytes (PMN) at 4 hr as assessed by histology and the levels of the PMN marker enzyme myeloperoxidase. 6-trans-LTB4 is a more potent PMN chemoattractant than 12(R)-HETE in the guinea pig dermis but is far less potent than LTB4. Pharmacological interdiction of leukotriene production or receptor binding should take into account the proinflammatory activity of 6-trans-LTB4.

Animals↗

Modulation of the chemotactic properties of complement fragments C5a and C3 by the anti-inflammatory agent, SC-41930.

Cleavage of the fifth component of complement yields C5a, a potent neutrophil (PMN) and eosinophil chemoattractant, and modulator of microvascular permeability. Similarly, but to a lesser degree, C3 increases vascular permeability and histamine release. SC-41930 (7-[3-(4-acetyl-3-methoxy-2-propylphenoxy)-propoxy]-3,4-dihydro-8- propyl- 2H-1-benzopyran-2-carboxylic acid), an orally-active antiinflammatory agent was tested in an in vivo model of dermal PMN chemotaxis induced by r-hu-C5a and hu-C3. Intradermal injection of C5a in the guinea pig resulted in a significant dose-dependent influx of PMNs at 4 hours as assessed by the dermal levels of myeloperoxidase (MPO). SC-41930 (20 mg/kg) given orally to guinea pigs with intradermal injections of 1 microgram C5a significantly (p less than 0.001) reduced dermal MPO content. SC-41930 was less potent against C3, requiring 40 mg/kg to significantly reduce dermal MPO levels. Agents such as SC-41930, which nullify complement's proinflammatory properties, may well have therapeutic potential.

Animals↗

Effect of the leukotriene B4 receptor antagonist, SC-41930, on experimental allergic encephalomyelitis (EAE) in the guinea pig.

The accepted model for the human demyelinating disease, multiple sclerosis (MS), is experimental allergic encephalomyelitis (EAE). We assessed the ability of SC-41930(7-[3(4-acetyl-3-methoxy-2-propyl-phenoxy)-propoxy]- 3,4-dihydro-8-propyl-2H-1-benzopyran-2-carboxyl acid), to modulate the symptoms of acute EAE generated in guinea pigs. Animals were pretreated with SC-41930 (20 mg/kg, i.p.) for two days followed by thrice-weekly maintenance. At day 52, a significant number of the SC-41930-treated animals were alive as compared to EAE alone. Control animals had an increase in body weight while EAE animals lost over 20% (p less than 0.5) of their body weight by day 18. SC-41930-treatment significantly reduced, but did not completely inhibit the cachectic response. The results indirectly implicate LTB4 in the pathogenesis of EAE. Agents that modify this model be useful in the treatment of human MS.

Animals↗

Membrane fluctuations in erythrocytes are linked to MgATP-dependent dynamic assembly of the membrane skeleton.

The observation of low-frequency fluctuations of the cell membrane in erythrocytes and in several nucleated cells suggests that this phenomenon may be a general property of the living cell. A study of these fluctuations in human erythrocytes and its ghosts has now been carried out using a novel optical method based on point dark field microscopy. We have demonstrated that the reestablishment of membrane fluctuations in erythrocyte ghosts is dependent on MgATP but does not necessarily require the restoration of the biconcave shape. The results imply that the dominant component of membrane fluctuations are metabolically dependent and suggest the existence of a dynamic mechano-chemical coupling within the membrane skeleton network induced by MgATP.

Adenosine Triphosphate↗

The Pawtucket Heart Health Program. Influencing adolescent eating patterns.

The Pawtucket Heart Health Program, a research effort testing a process of community activation for cardiovascular risk factor behavior change, risk factor change, and coronary heart disease event rate change, utilizes risk factor behavior change programs for the entire population of a northeastern city. A diversity of nutrition programs designed to teach new skills and to alter the nutrition environment have been delivered. These include group programs, highlighting restaurant menus, labeling grocery shelf items, screening for blood cholesterol levels accompanied by nutritional counseling, and provision of programs in schools. In addition to standard curricula, the Heart Healthy Cook-Off for both junior high school and high school students has been developed. Students select recipes, make substitutions to lower fat, saturated fat, and cholesterol content, analyze original and substitution recipe nutrient content using a microcomputer and nutrient analysis software, and prepare the food. A panel of judges assesses presentation, taste, and health-promoting characteristics. In one junior high school class, cholesterol measure before and after the cook-off decreased by 10.7% among those with elevated cholesterol. The Heart Healthy Cook-Off is an education program that influences the culinary practices of children in an enjoyable, challenging format.

Adolescent↗

Effects of the prostaglandin analogue misoprostol on cell proliferation in the canine small intestine.

While there are several reports of prostaglandins of the E series being associated with increased mucosal mass in the stomach, their effects on the small intestine are less well documented. A microdissection-based technique was used to measure proliferation and crypt size in the duodenum, jejunum and ileum of dogs given the prostaglandin analogue misoprostol. Six test and six control animals were given an oral dose of 300 micrograms kg-1 day-1 of misoprostol for 11 weeks, a dose-duration combination chosen to optimize the development of gastric hyperplasia. Misoprostol increased both the area of the crypts (P less than 0.001) and the number of mitoses per crypt (P = 0.002) throughout the small intestine. The technique also demonstrated a significant gradient in crypt size and in crypt area from the duodenum to the ileum. There was no statistical interaction between misoprostol and the site studied, suggesting that this trophic effect was systemic or systemically mediated.

Animals↗

Quinidine-induced hepatotoxicity revisited.

Although quinidine has been widely used since the beginning of the century, quinidine-induced hepatotoxicity has been recently reported in the literature. We describe a reversible case of quinidine-induced hepatotoxicity. A 62-y-old male with a past medical history of atrial flutter and adult onset diabetes was admitted to the hospital with a 3-d history of diarrhea, nausea, fever, chills and palpitations. Past medications included 7.5 mg glyburide daily for 4 y, 0.25 mg digoxin daily for 3 w, 324 mg quinidine gluconate 3 times daily for 2 w, and 150 mg papaverine daily for 2 y. On admission, liver enzyme levels were elevated (SGOT 606, SGPT 1104). Quinidine was considered an etiologic agent and was discontinued after administration of 1 dose. The patient became afebrile within 48 h, liver enzyme levels gradually decreased, and the patient was discharged on day 6 of hospitalization. Repeat enzyme levels obtained 12 d after discharge were mostly within normal limits. The symptoms were atypical as described in the literature. We conclude that unexplained fever or elevated liver enzyme levels should alert the clinician to the possibility of quinidine-induced hepatotoxicity.

Chemical and Drug Induced Liver Injury↗

A controlled comparison of involuntarily hospitalized medication refusers and acceptors.

Involuntarily hospitalized psychiatric patients consecutively admitted over a six-month period who successfully refused medication (n = 37) are compared with a randomly selected group of medication-accepting patients committed during the same time period (n = 37). The overall refusal rate was 15.6 percent during the study period. Acceptors and refusers did not differ on age, sex, diagnosis, ethnicity, marital status, or preadmission living status. Differences between the groups indicate that refusers are sicker and lower functioning, are more behaviorally acute on the ward, and stay in the hospital twice as long as acceptors. Refusers also have a significantly negative impact on the overall ward milieu. The impact of institutional factors on the rate and outcome from mediation refusal are discussed.

Adult↗