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Biomedical subjects

J Davis

Publications and source records attributed to J Davis.

At least 271 records · Page 15Linked to original sources
PubMed1993

Mice expressing a bovine basic fibroblast growth factor transgene in the brain show increased resistance to hypoxemic-ischemic cerebral damage.

BACKGROUND AND PURPOSE: Cerebral intraventricular infusion of acidic or basic fibroblast growth factor has been shown to attenuate ischemic damage to hippocampal CA1 neurons in the gerbil. The purpose of the present study was to determine if the basic fibroblast growth factor transgenic mouse has an enhanced ability to resist the effects of severe cerebral hypoxemia-oligemia. METHODS: Mice that were transgenic for bovine basic fibroblast growth factor were exposed to right carotid artery ligation, hyperglycemia, and 20 minutes of 1% carbon monoxide. After 5 days' recovery, brains were examined for histological damage. RESULTS: Counts of CA1 neurons in the right hippocampus showed a significantly higher number of neurons per millimeter CA1 in hypoxic-ischemic transgenic mice compared with nontransgenic controls (transgenic, 260 +/- 33; nontransgenic, 151 +/- 37 neurons per millimeter CA1; P < .05). CONCLUSIONS: The results indicate that basic fibroblast growth factor transgenic mice, as judged by CA1 hippocampal neuronal survival, have an enhanced ability to resist the effects of a complex hypoxic-ischemic cerebral insult.

Animals↗
PubMed1993

A comparison of pentastarch and lactated Ringer's solution in the resuscitation of patients with hemorrhagic shock.

Pentastarch is a colloid that is chemically similar to Hetastarch. It has a shorter half-life (12 hr), and produces volume expansion at least 1.5 times the administered volume. We compared Pentastarch to Ringer's lactate in 41 patients (21 Pentastarch, 20 Ringer's lactate) presenting with hemorrhagic shock. The groups were similar in age, sex, race, and type of injury. Significantly less volume of Pentastarch was required initially to resuscitate to a normal blood pressure and urine output than Ringer's lactate (P < 0.005). Coagulation parameters (prothrombin time, partial thromboplastin time, fibrinogen, and factor VIII) were measured for 48 hr post-resuscitation, and no abnormalities were noted in the Pentastarch group. Serum albumin was the same in both groups throughout the study period; however, serum colloid oncotic pressure was elevated at 1 hr post-resuscitation in the Pentastarch group (P < 0.005). There was no difference in ventilatory parameters, blood gases, pulmonary function tests, ventilator days, or hospital days between the two groups. We conclude that Pentastarch is safe and effective for the initial resuscitation from hemorrhagic shock.

Blood Coagulation↗
PubMed1993

Aspiration of foreign materials in children while under general anesthesia for dental extractions.

Airway aspiration of foreign materials in children and adults is probably more common than has been supposed. This study investigated the possibility of such aspiration in children while under general anesthesia for dental extractions. A radiopaque fluid was used to coat the oral tissues and showed that a significant number of children did aspirate material into the trachea, bronchi, and occasionally even lung tissue. The notion that safety may be improved by operating with the patient in the supine position was not confirmed. While careful placement of an oropharyngeal pack may prevent solid material from entering the trachea and bronchi, it should be realized that fluids such as blood, saliva, and pus could still contaminate the airway.

Anesthesia, Dental↗
PubMed1993

Comparison of stool containment in cloth and single-use diapers using a simulated infant feces.

Single-use diapers and cloth diapers with vinyl pants were compared for their relative abilities to contain stool within the diaper. Artificial feces with carbon black as an additive allowed a quantitative measure of fecal containment by image analysis in 60 infants. This method showed complete containment of feces in the diaper in 50% of the single-use diapers whereas only 10% of the cloth diapers showed complete containment. In infants where the border of the vinyl pants was used as the boundary of containment with the cloth diapers, complete containment occurred only 33% of the time. Fluorescein dye ratings for containment/leakage in 69 infants showed that 83% of single-use diapers and 30% of the cloth diapers were rated as having no or minor leakage of feces. Cultures were taken of laundered vinyl pants that had previously been used over cloth diapers to determine microbial contamination. Thirty-nine percent of the pants contained Gram-negative, lactose-fermenting bacilli indicating fecal contamination. This study comparing single-use and cloth diapers for containment of artificial feces by use of image analysis and fluorescein dye ratings showed better containment by single-use diapers. The study also raises the question of possible spread of feces-borne pathogens by the vinyl pants used over cloth diapers, particularly in a day-care center.

Bacteria↗
PubMed1992

Effects of long-acting nifedipine on casual office blood pressure measurements, 24-hour ambulatory blood pressure profiles, exercise parameters and left ventricular mass and function in black patients with mild to moderate systemic hypertension.

Thirty-nine black patients with mild to moderate hypertension were treated for 1 year with various long-acting preparations of nifedipine, during which time serial changes in 24-hour ambulatory blood pressure (BP), exercise performance, left ventricular (LV) mass index and LV systolic function were evaluated. Mean 24-hour ambulatory BP decreased from 156 +/- 15/99 +/- 8 to 125 +/- 10/79 +/- 6 mm Hg at 1 year (p less than 0.0001). LV mass index decreased from 130 +/- 40 to 114 +/- 39 g/m2 at 6 weeks (p less than 0.005) and to 95 +/- 32 at 1 year (p less than 0.0001). There was a significant reduction in septal and posterior wall thickness from 11.0 +/- 2.0 to 9.3 +/- 2.0 mm (p less than 0.0001) and from 10.9 +/- 2.0 to 9.3 +/- 2.0 mm (p less than 0.005), respectively. Cardiac index and fractional shortening changed insignificantly from 2.9 +/- 0.7 to 2.9 +/- 0.6 liters/min/m2, and from 35 +/- 5 to 36 +/- 6%, respectively. At 1 year, using a modified Bruce protocol, exercise time increased from 691 +/- 138 to 845 +/- 183 seconds (p less than 0.05); peak exercise and 1 minute post-effort systolic BP decreased from 240 +/- 26 to 200 +/- 21 mm Hg and from 221 +/- 27 to 169 +/- 32 mm Hg (p less than 0.05), respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1992

Vitamin E protects nerve cells from amyloid beta protein toxicity.

The amyloid beta protein (ABP) is a 40 to 42 amino acid peptide which accumulates in Alzheimer's disease plaques. It has been demonstrated that this peptide and a fragment derived from it are cytotoxic for cultured cortical nerve cells. It is shown here that ABP and an internal fragment encompassing residues 25 to 35 (beta 25-35) are cytotoxic to a clone of PC12 cells at concentrations above 1 x 10(-9)M and to several other cell lines at higher concentrations. Between 10(-9) and 10(-11) M beta 25-35 protects PC12 cells from glutamate toxicity. The antioxidant and free radical scavenger vitamin E inhibits ABP induced cell death. These results have implications regarding the prevention and treatment of Alzheimer's disease.

Amyloid beta-Peptides↗
PubMed1992

Synthesis and in vitro biological profile of all four isomers of the potent muscarinic agonist 3-(3-methyl-1,2,4-oxadiazol-5-yl)-1-azabicyclo[2.2.1]heptane.

The four stereoisomers of the muscarinic agonist 7 have been synthesized from enantiomerically pure exo-azanorbornane esters (13a,b). The esters were obtained in optically active form by separation of the carboxamide diastereomers 12a,b, formed from the borane complex of exo-azanorbornane-3-carboxylate 10 and a chiral amine auxiliary. Using the known chirality of (R)-alpha-methylbenzylamine, an X-ray analysis was accomplished on 12a in order to determine the absolute configuration of the azanorbornane C4 chiral center. Each of the chiral esters 13a,b was separately transformed into the oxadiazoles with concomitant epimerization at C3 of the azanorbornane ring to afford the thermodynamic equilibrium mixture of isomers. Chromatographic separation followed by analysis of each isomer by NMR and GC allowed the absolute stereochemistry of all four isomers of 7 to be confirmed. Full biological evaluation in biochemical and pharmacological assays revealed that the 3R,4R isomer was the most active on receptor binding studies and the most potent on the pharmacological preparations, showing a 50-fold increase in potency at the M2 and M3 sites compared to M1.

Animals↗
PubMed1992

A longitudinal study of plasma cortisol and depressive symptomatology by random regression analysis.

The authors utilized a random regression model to test the longitudinal relationship between depressive symptomatology and plasma cortisol levels obtained before and after the administration of dexamethasone in 62 affectively ill inpatients. This statistical model for longitudinal studies permits the inclusion of subjects with incomplete data as well as subjects measured at different time points. The most significant relationships were found between decreases in depressive symptoms and decreases in the 8:30 AM predexamethasone and the 4:00 PM postdexamethasone cortisol values. Patients were also classified as responders or nonresponders, and the rate of change in several plasma cortisol measures were separately analyzed for these two groups. No differences in the rate of change in plasma cortisol levels were found between responders and nonresponders. These results suggest that the decreases in cortisol production associated with clinical improvement may be partially explained by a regression toward the mean effect. Some of the possible explanations for these results are discussed.

Adult↗
PubMed1992

A randomised study comparing standard dose carboplatin with chlorambucil and carboplatin in advanced ovarian cancer.

A total of 161 previously untreated patients with FIGO stage III or IV epithelial ovarian cancer were randomised after surgery to receive six courses of either carboplatin 400 mg m-2 alone (Arm A) or carboplatin 300 mg m-2 with chlorambucil 10 mg day-1 for 7 days (Arm B). The median progression free survival (PFS) was similar: arm A: 45 weeks; arm B: 61 weeks (P = 0.830). Multivariate Cox regression analysis showed that the extent of residual disease and performance status were the most important prognostic factors for PFS. Fifty-two per cent of patients received dose escalations based on nadir blood counts, and 89% of all dose adjustments were made according to protocol. Failure to achieve a significant degree of leucopenia was associated with worse progression free survival (P less than 0.001). A total of 29.4% of patients fall into this category. The median survival was similar in both arms, i.e. 75 weeks. It is unlikely that there is any major clinical advantage to adding chlorambucil to single agent carboplatin for the management of advanced ovarian cancer, but whether used in combination or a single agent, the dose of carboplatin should be sufficient to cause at least grade I leucopenia. This may best be achieved by determining the initial dose based on renal function, and then adjusting subsequent doses according to nadir blood counts.

Adult↗
PubMed1992

Treatment of acute graft-versus-host disease with a nonmitogenic anti-CD3 monoclonal antibody.

Treatment with the monoclonal antibody OKT3 specific for the CD3 complex associated with the T cell antigen receptor can reverse acute rejection of human renal allografts. However, efficacy of anti-CD3 antibodies for treatment of patients with acute graft-versus-host disease after marrow transplantation has not been established. The dose-limiting side effects resulting from T cell activation induced by some anti-CD3 antibodies in vivo have discouraged their use for this application. We now report a phase I-II study of GVHD treatment with the anti-CD3 antibody BC3, a monoclonal murine IgG2b that, unlike OKT3, does not activate T cells. Fourteen patients were treated with BC3 after progression of acute GVHD despite treatment with cyclosporine and corticosteroids, and three patients received BC3 as primary treatment for GVHD. BC3 was administered at a dose of 0.1 or 0.2 mg/kg/day for seven or eight days. Five patients achieved complete resolution of GVHD, eight patients had partial improvement, two patients had no change, and two patients had progression of GVHD on therapy. Responses were sustained in 8 of 13 patients. Mild chills, fever, hypertension, and chest discomfort occurred in various combinations following 6 of 17 (35%) initial infusions of BC3 and following 4 of 99 (4%) subsequent infusions. In each instance it was possible to continue BC3 therapy without adjusting the dose or treatment schedule. In each patient treated, the absolute count of peripheral blood lymphocytes decreased transiently but returned to baseline within 22 hr after the first infusion. Circulating T cells had surface CD3 molecules saturated by the infused antibody in all but one patient. Four patients survived longer than one year after treatment with antibody BC3, and 13 patients died of infection or organ failure. Administration of the nonmitogenic anti-CD3 antibody BC3 was associated with improvement in the clinical manifestations of GVHD with minimal acute toxicity. Efficacy of antibody treatment did not depend on depletion of circulating T cells. Therefore, antibody BC3 may be achieving therapeutic immunosuppression by modulating T cell function. Controlled studies in patients treated earlier in the course of GVHD should determine whether antibody BC3 can improve survival.

Adult↗
PubMed1992

T cell responses to repeat and non-repeat regions of the circumsporozoite protein detected in volunteers immunized with Plasmodium falciparum sporozoites.

The design of a malarial vaccine based on the circumsporozoite (CS) protein, a major surface antigen of the sporozoite stage of the malaria parasite, requires the identification of T and B cell epitopes for inclusion in recombinant or synthetic vaccine candidates. We have investigated the specificity and function of a series of T cell clones, derived from volunteers immunized with Plasmodium falciparum sporozoites, in an effort to identify relevant epitopes in the immune response to the pre-erythrocytic stages of the parasite. CD4+ T cell clones were obtained which specifically recognized a repetitive epitope located in the 5' repeat region of the CS protein. This epitope, when conjugated to the 3' repeat region in a synthetic MAPs construct, induced high titers of antisporozoite antibodies in C57BL mice. A second T cell epitope, which mapped to aa 326-345 of the carboxy terminal, was recognized by lytic, as well as non-lytic, CD4+ T cells derived from the sporozoite-immunized volunteers. The demonstration of CD4+ CTL in the human volunteers, and the recent studies in the rodent model (Renia et al., 1991; Tsuji et al., 1990), suggest that CS-specific CD4+ T cells, in addition to their indirect role as helper cells in the induction of antibody and CD8+ effector cells, may also play a direct role in protection against sporozoite challenge by targeting EEF within the liver.

Amino Acid Sequence↗
PubMed1992

Societal influences on a thinner body size in children.

This study was designed to examine whether educational textbook illustrations portray children thinner since the turn of the century. 50 undergraduates each rated 54 third-grade text pictures (3 of boys and 3 of girls in each decade since 1900) on a thinness scale. Analysis indicated a significant trend in thinness for girls but not for boys. Concerns are raised about a connection between educational illustrations of children and eating disorders.

Adolescent↗
PubMed1992

A modified Da Fano silver stain for demonstration of neurons and dendrites in glycol methacrylate-embedded brain tissue.

Golgi impregnation techniques are commonly used for characterization of neurons and their dendritic and axonal processes. Most of the widely used techniques require processing of fresh brain tissues, which limits the amount of material available for study. Additionally, the stained blocks must be subsequently embedded in paraffin, which produces considerable cellular shrinkage and distortion artifacts. Modification by one investigator of an early silver impregnation technique, designed to demonstrate the Golgi apparatus, allowed demonstration of neurons and their dendritic processes. Our further modification of the later technique, along with embedding of the stained tissue in glycol methacrylate, permits detailed examination of neurons and their processes in formaldehyde-fixed neonatal human brains. In cerebellar sections, this modified technique impregnates nearly all Purkinje cells, elucidating the fine structural detail of the developing neuronal dendritic tree and spines.

Brain↗