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Biomedical subjects

S Levin

Publications and source records attributed to S Levin.

At least 55 records · Page 3Linked to original sources

Effects of misoprostol on cell migration and transit in the dog stomach.

Prostaglandins of the E series increase stomach mucosal mass by inducing hyperplasia, which could be the result either of increased cell production or of decreased cell loss. This report describes an investigation of the effect of the prostaglandin E1 analogue, misoprostol, on cell migration and transit. 3H-thymidine was used to label those cells synthesizing deoxyribonucleic acid in dogs that had been given an oral dose of 300 micrograms/kg per day misoprostol for 11 weeks. The animals were killed at timed intervals, and tissue from the gastric fundus was prepared for autoradiography. The distribution of labeled cells at various times after labeling was used to follow the movement of the wave of label and to calculate median cell migration rates and transit times. The migration rate of cells toward the gastric lumen was significantly increased from 1.4 +/- 0.3 to 3.6 +/- 0.6 cell positions per day in the misoprostol-treated group (p less than 0.001); however, the gland length (from the most basal mucous neck cell to the luminal surface) was also increased (from 52.1 +/- 1.1 to 74.0 +/- 1.6; p less than 0.001), thus there was no significant difference in the (transit) time taken for cells to reach the top of the gland (control, 17.5 +/- 9.8 days; test, 12.2 +/- 7.1 days).

Alprostadil

Heart healthy cook-offs in home economics classes: an evaluation with junior high school students.

The Pawtucket Heart Health program works closely with the 23 parochial and public schools in Pawtucket, R.I., to educate students and teachers about heart health promotion. As part of that partnership, the PHHP developed a program to teach junior high school home economics students about nutrition, food purchasing techniques, and heart healthy cooking methods. In this Heart Healthy Cook-off program, the PHHP distributes recipe guidelines to home economics teachers who instruct students in recipe modification, food preparation, and presentation. Students choose recipes and make heart healthy substitutions to lower fat and sodium content. Recipes are analyzed for nutrient content by the PHHP and returned to the students with suggestions for lowering fat and sodium if necessary. Final recipes are judged for heart healthiness by a nutritionist and for taste by a panel of judges. Prizes are awarded to students with winning recipes. Before and after the Cook-offs, classes host a blood cholesterol SCORE (screening, counseling, and referral event) where students learn about their blood cholesterol level and its relationship to dietary intake. In 1988-1989, 105 junior high school students participated in the Cook-off/SCORE program. Forty percent had elevated blood cholesterol levels of 170 mg/dl or above. A statistically significant decrease in blood cholesterol levels was observed during a 12-week time period. The Cook-off is a fun, effective program for teaching secondary school students about heart healthy eating habits.

Adolescent

Prostaglandins and the dog stomach: effects of misoprostol on the proportion of mucosa to muscle and on the proportion of different epithelial cell types.

Dogs were given an oral dose of 300 micrograms/kg/day of the prostaglandin E1 analogue, misoprostol for 11 weeks. The relative areas of the main components of the fundus and antrum per unit area of serosa were quantified. While the volume occupied by the muscle layers did not change, there was an increase in mucosal volume in both sites. The relative volume fraction of the main mucosal cell types was then determined by a point counting technique. Misoprostol very highly significantly increased the fraction of mucosal volume occupied by surface mucus cells, and also significantly decreased the volume fraction of the parietal cells.

Alprostadil

The effects of the prostaglandin analogue, misoprostol, on cell proliferation and cell migration in the canine stomach.

Increased mucosal mass is associated with prostaglandin administration, raising the question as to whether this is the consequence of increased cell production or decreased cell loss. 3H-thymidine was injected into 30 test dogs given 300 micrograms/kg/day of the prostaglandin E1 analogue, misoprostol, orally for 11 weeks, and into 30 dogs which had been given the vehicle alone. Six test and 6 control dogs were killed 1 h after thymidine labelling, and the remainder were killed subsequently at timed intervals to determine cell migration rates and transit times. Misoprostol significantly increased the stomach weight, but nonetheless did not significantly increase the labelling index, nevertheless, the number of labelled cells per gland was significantly increased, which was a consequence of the increased gland length. When the data was expressed as a gland cell production rate significant increases were thus observed. The migration rate of cells toward the gastric lumen increased one and a half times in the misoprostol-treated group; however, as the gland length also significantly increased, there was no significant difference in the transit time. It must be concluded that the hyperplasia associated with exogenous prostaglandins is the consequence of increased cell production, not decreased cell loss, and that previous reports to the contrary are the result of failure to allow for concomitant changes in the denominator of proliferative indices.

Alprostadil

Interferon system and natural killer cell activity in myasthenia gravis.

The autoimmune response in myasthenia gravis is well characterized, but little is known about the mechanisms initiating it. We have studied the interferon system and natural killer cell activity in 25 patients with myasthenia gravis and compared them to 68 healthy subjects and 96 patients with acute viral infections. Forty-four per cent of patients had circulating interferon (greater than 16 mu/ml), and in a similar proportion their peripheral blood mononuclear cells were in an antiviral state, i.e., showed low levels of viral replication when infected by vesicular stomatitis virus. Spontaneous in vitro interferon production by patients' peripheral blood mononuclear cells was also common (greater than 10 mu/ml, 32 per cent), while the response to the alpha-interferon inducer poly I:C was lower than expected, possibly reflecting the already high state of activation of the interferon system. These results were essentially similar to those obtained in patients with viral illnesses and differed significantly from healthy controls. In many myasthenia gravis patients (16 of 22, 73 per cent), a markedly deficient natural killer cell activity was found, with a median cytotoxicity of 6.5 per cent compared to 29 per cent in healthy subjects (p less than 0.005). Thus, many patients with myasthenia gravis have evidence of an activated interferon system and defective natural killer cell activity, suggesting an occult viral infection or reflecting nonspecific stimulation which may nevertheless contribute to the pathogenesis of the autoimmune response.

Acute Disease

Effect of the leukotriene B4 receptor antagonist SC-41930 on colonic inflammation in rat, guinea pig and rabbit.

Inflammatory bowel disease is a chronic inflammatory disorder of the gastrointestinal tract that includes ulcerative colitis and Crohn's disease. Leukotriene B4 is thought to be a prominent proinflammatory mediator in these diseases, in that leukotriene B4 levels are increased in the colonic mucosa of inflammatory bowel disease patients and there is increased polymorphonuclear leukocyte infiltration of these tissues. We evaluated the efficacy of 7-[3-(4-acetyl-3-methoxy-2-propylphenoxy)-3,4-dihydro-8-propyl -2H-1-benzopyran-2-carboxylic acid (SC-41930), a potent, orally active leukotriene B4 receptor antagonist, in a model of inflammatory bowel disease. Colonic mucosal inflammation was induced in rats, guinea pig and rabbits by rectal instillation of a dilute solution of acetic acid. Twenty-four hours later, mucosal levels of myeloperoxidase (a marker enzyme for neutrophil infiltration) and extravasation of i.v. administered Evans blue dye (a marker of vascular disruption and increased permeability) were measured. Tissues were also evaluated histologically. The animals received either SC-41930 or vehicle, intrarectally, 30 min after or 1 hr before and 1 hr after the acetic acid. When given 30 min after acetic acid instillation SC-41930 prevented the rise in myeloperoxidase and dye extravasation observed in the acetic acid inflammed tissue. The SC-41930-treated tissues were less edematous and had fewer neutrophils within the subepithelial space. Median effective dose (ED50) values for vascular protection were approximately 20 mg/kg for both rat and guinea pig. ED50 values for inhibition of granulocyte accumulation were 20 mg/kg for rat, 24 mg/kg for guinea pig and 30 mg/kg for rabbit. These data indicate that SC-41930 is effective locally to prevent acute colonic inflammation.

Animals

Arthrodesis of the metacarpophalangeal joint of the thumb in children and adults. Adjunctive treatment of thumb-in-palm deformity in cerebral palsy.

A hypermobile hyperextension or hyperflexion deformity of the metacarpophalangeal (MCP) joint associated with thumb-in-palm deformity in 90 patients affected by cerebral palsy was treated by arthrodesis with or without soft-tissue procedures. Twenty-two of these patients were adults with closed physes, and 68 were children or adolescents with open growth plates. The MCP joint fusion was usually accompanied by intrinsic muscle lengthening and/or extrinsic tendon transfer, but occasionally it was the only procedure performed to diminish the thumb-in-palm position. Even in four-year-olds, joint fusion was a predictable procedure to establish stability of that joint without disturbing longitudinal or circumferential growth. Measurable function was improved to a mild or moderate degree in 44 of the 50 children who were followed to maturity. Eighteen of the 68 children were unavailable for follow-up evaluation. Six of the 50 followed patients showed no functional improvement, although arthrodesis of the MCP joint occurred in four of the six. The other two patients were operated on when they were 12 years of age and developed a fibrous union that was painless and stable when they were adults. Even those patients who had no functional improvement did have improved appearance and easier control of the affected hand when it was manipulated by the opposite hand. The children were followed to maturity with age-matched cerebral palsy control patients. There was no significant disturbance in growth of those thumbs that had MCP joint fusion when the physes were open.

Adolescent

Randomized study of intravenous/oral ciprofloxacin versus ceftazidime in the treatment of hospital and nursing home patients with lower respiratory tract infections.

This study determined the efficacy of intravenous ciprofloxacin in the treatment of institutionalized patients with lower respiratory tract infections. Hospitalized adults with hospital/nursing home-acquired pneumonia were randomly assigned to receive either intravenous ciprofloxacin or ceftazidime. When deemed feasible, therapy was changed to oral ciprofloxacin for patients who received ciprofloxacin intravenously or to any alternative oral therapy for patients who received ceftazidime. All 23 patients who received ciprofloxacin had a favorable response versus 15 of 21 patients who received ceftazidime (p less than 0.025). One patient with a favorable response to ceftazidime developed a superinfection and one patient had a relapse during subsequent alternative oral therapy. However, patients who received ceftazidime were more severely ill than those who received ciprofloxacin on the basis of APACHE II scores.

Administration, Oral

Thiamine deficiency in utero alters response to ethanol in adulthood.

To determine whether prenatal thiamine deficiency, a frequent concomitant of alcoholism, reduces the response to ethanol during adulthood in the rat as does ethanol exposure in utero (Abel et al. 1981), pregnant Sprague-Dawley rats received either control or thiamine deficient diets together with daily injections of the thiamine antagonist pyrithiamine. At 7 months of age, male offspring were exposed to precisely regulated ethanol vapor concentrations in an inhalation chamber for 24 h and blood ethanol concentrations (BECs) and ethanol-induced intoxication were determined. Prenatally thiamine deficient rats and controls were indistinguishable in terms of appearance, body and liver weights, and the ratios of liver to body weight and brain to liver weight. However, total body water was significantly greater, and BECs and behavioral impairment were decreased, in the experimental rats. These findings indicate that prenatal thiamine deprivation is associated with reduced pharmacologic effect of ethanol as a result of increases in its volume of distribution and rate of metabolism.

Animals

The effect of leukotriene-B4 receptor antagonist, SC-41930, on acetic acid-induced colonic inflammation.

SC-41930, 7-[3-(4-acetyl-3-methoxy-2-propylphenoxy)-propoxy]-3,4-dihydro-8-p ropyl- 2H-1-benzopyran-2-carboxylic acid, is a potent in vitro leukotriene-B4 (LTB4) receptor antagonist. LTB4 levels are elevated in colonic tissue of inflammatory bowel disease (IBD) patients which may account for the high degree of neutrophil (PMN) infiltration. The guinea pig acetic acid-induced colonic inflammation model has characteristics of IBD including PMN infiltration, edema, ulceration and necrosis. The model was used to evaluate the effect of SC-41930. SC-41930 was given orally, 30 min before and after intrarectal administration of 3% acetic acid. The PMN marker enzyme, myeloperoxidase, was measured along with histological evaluation to assess inflammation. Both parameters showed significantly less inflammation in SC-41930 treated animals with an oral ED50 of 20 mg/kg. These study results with an LTB4 receptor antagonist indicate a role for LTB4 in colonic inflammation and that an LTB4 receptor antagonist may be beneficial for treatment of IBD.

Acetates

Possible role of natural cytotoxic activity in the pathogenesis of AIDS.

In an attempt to assess the role of immune cytotoxic activity in the sequence of events leading to the acquired immunodeficiency syndrome (AIDS), natural cytotoxic activity was studied in 17 asymptomatic homosexual males, seropositive for anti-human immunodeficiency virus (HIV) antibodies, as compared to 16 of their seronegative counterparts and to 14 control healthy heterosexual individuals. Cell (contact)-mediated cytotoxicity (CMC) as well as cytotoxin (CTX) production by lipopolysaccharide (LPS)-stimulated, phytohemagglutinin (PHA)-stimulated, HeLa tumor cell-stimulated, and unstimulated peripheral blood mononuclear cells (PBMC) were determined using HeLa cell monolayer cultures, sensitized with cycloheximide, as targets. The CMC was markedly enhanced in the seropositive group (28 +/- 21 (mean +/- SD) lytic units/10(6) PBMC) as compared to the seronegative group (17 +/- 7; P less than 0.005) and to the heterosexual group (13 +/- 6; P less than 0.05). Likewise, CTX production by unstimulated PBMC from seropositive homosexuals (19 +/- 26 units/ml) was higher than that observed in the other groups (both 4 +/- 4 units/ml; P less than 0.05). CTX production by PHA-stimulated, LPS-stimulated, and HeLa cell-stimulated PBMC was significantly enhanced in both the seropositive and seronegative groups in comparison to the normal heterosexual controls. These results suggest that increased cytotoxic activity may be present in homosexuals prior to their exposure to HIV, and may be further enhanced after HIV infection.

Acquired Immunodeficiency Syndrome

The interferon system in subacute sclerosing panencephalitis and its response to isoprinosine.

Plasma interferon activity (IFN) and its spontaneous and stimulated production by peripheral blood mononuclear cells (PBMC) was studied in 11 patients with subacute sclerosing panencephalitis (SSPE) and age-matched healthy controls. The patients, similar to the healthy controls, had no detectable plasma IFN activity. However, their PBMC failed to produce IFN in response to stimulation with poly I:C and PHA. After isoprinosine administration to 7 patients for several days a significant increase in plasma IFN activity was observed and their PBMC responded to stimulation by producing IFN. The long-term effect of isoprinosine on the IFN response was evaluated in 3 patients who had been treated for 57-88 days. Induction of the abolished IFN production was observed with initiation of therapy. However, discontinuation of isoprinosine for 10 days resulted in recurrence of the inactivation state of the IFN system.

Adolescent

Contributions of clinical neuropsychology to the study of schizophrenia.

Clinical neuropsychological findings are examined with respect to competing hypotheses about localized neuropathology in schizophrenia. Two general models of structural and functional impairment are described. The first addresses deficits in cortical/subcortical processes concerned with arousal, attention, and higher cortical functions. The second addresses impairments in the balance of lateralized functions consistent with left hemisphere overactivation. Empirical data provide support for both models, and suggest that the explanatory power of these models may vary when they are applied to different subtypes of schizophrenia.

Cerebral Cortex

Clinical impact of rapid identification and susceptibility testing of bacterial blood culture isolates.

Two hundred twenty-six patients with bacteremia were prospectively enrolled in a randomized trial that was performed to determine the clinical impact of the receipt of in vitro microbiological data by the physician soon after organism detection as opposed to having the physicians wait until similar data were available by routine methods. Identification and antibiotic susceptibility patterns of 110 isolates were determined by direct inoculation of the Vitek AutoMicrobic system (Vitek Systems, Inc., Hazelwood, Mo.) with a sample from a positive blood culture vial. One hundred sixteen isolates were processed by routine methods. Microbiological results were available within an average of 8.8 h by the direct method versus an average of 48 h by the routine method. In both groups an infectious disease fellow used the information to make therapeutic recommendations to the responsible physician. When compared with that provided by the routine method, the information provided by the direct method was significantly more likely to result in an initiation of antibiotic therapy, a change to more effective therapy, or a change to less expensive therapy. Recommendations were significantly more likely to be followed in patients whose isolates were processed by the direct method versus the routine method. A projected savings of $158 per patient was estimated for the patients who were changed to less expensive therapy or in whom antibiotics were discontinued because results were available sooner. These cost savings, coupled with changes in therapy made for reasons of efficacy, support the usefulness of the earlier reporting of the identity and antibiotic susceptibility patterns of bacterial blood culture isolates.

Bacteria