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Biomedical subjects

J M Davis

Publications and source records attributed to J M Davis.

At least 361 records · Page 20Linked to original sources
PubMed1990

Response to treatment with antidepressants of patients with severe or moderate nonpsychotic depression and of patients with psychotic depression.

Hospitalized patients were divided into nonpsychotic severely depressed (N = 53), nonpsychotic moderately depressed (N = 54), and psychotic depressed (N = 25) groups and treated with either imipramine or amitriptyline, up to 250 mg/day, for 4 weeks. Good response occurred in 39% of the 38 severely depressed, 67% of the 49 moderately depressed, and 32% of the 19 psychotic depressed patients who completed treatment. The response of the patients with nonpsychotic severe depression did not differ significantly from the response of those with psychotic depression, and both groups fared worse than the group with nonpsychotic moderate depression.

Adult↗
PubMed1990

Early pulmonary changes associated with high-frequency jet ventilation in newborn piglets.

To assess the short-term effects of high-frequency jet ventilation (HFJV) on the neonatal lung, 28 newborn piglets were studied. Nine piglets were unventilated except during brief pulmonary measurements, nine animals were conventionally ventilated (arterial CO2 tension 35-45 torr, arterial O2 tension 70-80 torr) for 4 h, and 10 piglets were ventilated with HFJV for the same period. Pulmonary function was analyzed using a computerized technique and tracheobronchial aspirates were examined for biochemical indicators of lung injury; after 4 h, bronchoalveolar lavage was obtained for surfactant composition and activity, and lung sections were examined by light and electron microscopy. Results showed that HFJV provided adequate ventilation at lower inspiratory pressure compared with conventional ventilation (8.6 +/- 0.3 versus 13.8 +/- 1.3 cm H2O; p less than 0.01), while pulmonary mechanics did not vary significantly among the three animal groups. Tracheobronchial aspirates from HFJV animals had higher elastase activity versus unventilated piglets (118.5 +/- 14.1 versus 57.7 +/- 8.4 micrograms/mL; p less than 0.01), as well as higher albumin concentration versus unventilated animals (94.2 +/- 18.7 versus 23.2 +/- 6.5 micrograms/mL; p less than 0.01). In addition, there were small but statistically significant differences between all three groups in the distribution of surfactant phospholipids in bronchoalveolar lavage, although biophysical activity was normal. Scanning electron microscopy revealed flattening of Clara cells in the terminal bronchioles of HFJV animals due to loss of glycogen and secretory granules. These data indicate that despite lower peak inspiratory pressures, HFJV can cause subtle biochemical changes in lungs. Further studies are indicated to determine if these changes precede significant lung injury.

Animals↗
PubMed1990

The relationship between fibrosis and cancer in experimental animals exposed to asbestos and other fibers.

The association between occupational asbestos exposure and the development of both pulmonary fibrosis or asbestosis and pulmonary carcinomas is well documented. It has been suggested that the two pathological conditions are associated with asbestos-related carcinomas developing from areas of asbestosis and not occurring when exposure has been too low to produce this type of pulmonary scarring. Experimental inhalation studies so far published have not been designed to examine this association specifically, but many publications have reported that asbestos samples producing high levels of fibrosis is experimental animals are also very carcinogenic. Samples of asbestos or man-made fibers that produce little fibrosis also produce few tumors. These works are reviewed. In order to examine the association between fibrosis and tumor production in more detail, groups of animals with and without pulmonary tumors and with individual fibrosis measurements were assembled from a number of inhalation studies undertaken over a period of years at this Institute. It was found that animals with pulmonary tumors had almost double the amount of pulmonary fibrosis as animals of similar age that did not. In a few of the animals where tumors were found at an early stage of development, their origin from fibrotic areas could be confirmed, although in most cases where tumor deposits were widespread this was not possible. Experimental confirmation of the site of origin of most pulmonary tumors in asbestos-treated rats would require new studies with rats examined specifically at an age when early tumors would be expected.

Animals↗
PubMed1990

Is maintenance antiparkinsonian treatment necessary?

The authors designed a three-phase prospective trial in which only those patients who developed an acute, neuroleptic-induced extrapyramidal side effect (EPSE) received benztropine (BZ) at 2 mg i.m. and then 1 mg p.o. b.i.d. for 2 days after their symptoms were rated for severity and type (Preparatory Phase 1). They were then randomly assigned under double-blind conditions to continue BZ or be switched to placebo for 8 days (Experimental Phase 2). Finally in Phase 3 (Followup), all patients continued on placebo in a single-blind design until Day 30. If the patient re-experienced an acute EPSE that was of sufficient severity to require immediate BZ administration, he or she was rated, treated, and then dropped from the study. EPSE scores and dropout rates did not differ in Phase 2 between the placebo- and BZ-treated groups. Implications for the continuation, cessation, or intermittent use of antiparkinsonian (AP) drugs are discussed.

Adult↗
PubMed1990

Using elutriation to engineer bone marrow allografts.

We have used elutriation to deplete lymphocytes from the marrow allografts of 64 patients to date. The first phase I trial (1 x 10(6) lymphocytes/kg IBW) was designed to test the procedure for potential toxicities, most notably, graft failure. Study 2 (1 x 10(6) lymphocytes/kg, no CsA) was expected to reduce potential toxicity incurred from long term immunoprophylaxis while study 3 was aimed at reducing the incidence of GVHD by further reducing lymphocyte dose (5 x 10(5)/kg). Graft lymphocyte dose was based on morphologic determination and was subsequently confirmed by limiting dilution analysis and flow cytometry. Although grafts were standardized solely by lymphocyte dose, the product was more uniform than the original harvested BM with respect to other cell populations. Nearly all study I (n = 40) and study III (n = 20) patients engrafted with a median time to ANC greater than 500/ul of 19 days. Three of the 4 patients consecutively enrolled in study II failed to engraft, thus terminating the trial. While a moderate proportion of study I patients had AGVHD (44%) with attendant morbidity, only 20% of study III patients were found to have mild AGVHD (less than or equal to stage I). To date, this cohort has no organ or chronic GVHD and no GVHD-associated morbidity. Median follow-up times for patients in studies I and III are 27 and 11 months, respectively. Overall actuarial survival (n = 60) is 42% at 38 months (38% study I, 80% study III). Good prognosis study I patients experienced 45% actuarial survival versus 9% in the poor prognostic group. While lymphocyte depletion has been effective in reducing the incidence and severity of AGVHD, new strategies are needed to address the issue of disease relapse. As with other methods, lymphocyte depletion by elutriation caused an increased rate of leukemia relapse. The actuarial probability of remaining in remission for recipients of elutriated marrow containing 1 x 10(6) and 5 x 10(5) lymphocytes/kg, respectively, were 60% and 46% at 16 months. Elutriation provides a rapid, reproducible and flexible methodology for graft manipulation which has been effective in reducing the incidence and severity of AGVHD. However, if lymphocyte depletion is to fulfill its promise as a means of reducing the overall morbidity of allogeneic BMT, new strategies may be needed to address the issue of relapse. These may include changes in marrow ablative therapy and post-graft immunosuppression. Equally as important may be the ability to further manipulate accessory cells and lymphoid populations presently excluded from the graft.

Adult↗
PubMed1990

Elevated production of neutrophil leukotriene B4 precedes pulmonary failure in critically ill surgical patients.

Leukotriene B4, a potent neutrophil chemotactic factor, is also made by the neutrophil. Neutrophil function was studied in 12 patients at risk for the development of adult respiratory distress syndrome (ARDS) after admission to the surgical intensive care unit (ICU) to test the hypothesis that increased generation by the neutrophil generation of this mediator precedes the development of pulmonary failure. Peripheral blood neutrophils were tested for chemotaxis to f-met-leu-phe (fMLP) and leukotriene B4 (LTB4) and the generation of LTB4. Plasma was collected simultaneously for assay of C3a desArg levels. Five patients had ARDS a mean of 2.2 +/- 0.25 days after admission to the ICU. Neutrophil generation of LTB4 was significantly enhanced on ICU day 1 in these patients as compared with patients at risk for ARDS but not developing the syndrome (119.4 +/- 6.1 versus 101.0 +/- 5.1, per cent control, p less than 0.05). Chemotaxis to fMLP and LTB4 was significantly reduced in both groups of patients. However, neutrophil chemotaxis improved in patients who did not have pulmonary failure during the time in the ICU, whereas neutrophil chemotactic responsiveness worsened in patients who did have pulmonary failure. Plasma C3a desArg levels were significantly elevated over normal laboratory values on ICU day 1 in the ARDS patients (317.2 +/- 74.0 versus 132.0 +/- 16.0 milligrams per milliliter, p less than 0.01). These data indicate that LTB4 production by the neutrophil occurs concomitantly with complement activation, is a predictor of subsequent ARDS and may play a significant role in the development of pulmonary failure in critically ill surgical patients.

Chemotaxis, Leukocyte↗
PubMed1990

Risk assessment of the developmental neurotoxicity of lead.

Lead has long been recognized as a developmental neurotoxicant. Although no reasonable doubt exists about this qualitative characterization, quantitative aspects of the developmental neurotoxicity of lead have been more difficult to resolve. This paper focuses on two key issues in a risk assessment of lead: the blood lead level of concern, i.e., the lowest level of exposure associated with neurotoxic effects in children, and the magnitude and implications of such effects. The distinction between a threshold and a level of concern is also discussed, along with the issue of whether a threshold exists for lead-induced health effects.

Child↗
PubMed1990

Plasma HVA in psychiatric patients: longitudinal studies.

Plasma homovanillic acid (pHVA) was measured in 40 inpatients (25 schizophrenic and 15 nonschizophrenic patients) who underwent up to 3 weeks of drug washout. Schizophrenic patients were then treated with trifluoperazine for 4 weeks, and weekly behavioral and pHVA measures were obtained. The baseline pHVA had no relationship to age, sex, washout period, diagnosis, or behavioral rating scores. In schizophrenic patients, the baseline pHVA did not differ significantly from any value obtained during 4 weeks of treatment. Although there was significant improvement in clinical symptoms, this was not related to changes in pHVA. Further, changes in any of the four Brief Psychiatric Rating Scale (BPRS) factors (i.e., positive symptoms, negative symptoms, hostility/suspicion, or anxiety/depression) were not correlated with changes in pHVA. Although other studies have reported a positive correlation between pHVA and psychotic symptoms, results of this study suggest that any observed relationship between pHVA and psychosis must be carefully interpreted.

Homovanillic Acid↗
PubMed1990

Density-gradient separation of autologous bone marrow grafts before ex vivo purging with 4-hydroperoxycyclophosphamide.

We found in previous studies that the cytotoxicity of 4-hydroperoxycyclophosphamide (4-HC) toward normal and malignant cells in autologous bone marrow grafts was modulated by the variable erythrocyte content of the incubation mixture. This affected both the kinetics of engraftment and the probability of leukemic relapse. To decrease this variability in 4-HC cytotoxicity, we initiated a trial of density-gradient separation of the autografts to remove erythrocytes and other mature blood cells before the 4-HC treatment. A series of 64 consecutive patients was studied. Light-density (sp. gr. much less than 1.077 g/ml) cells were isolated in a 2-step procedure by Ficoll-diatrizoate separation of previously isolated buffy-coat cells. Overall cell recovery after buffy-coat and gradient separations was 28.9 +/- 11.7% ( +/- SD). These cells were then treated with 60 micrograms/ml of 4-HC. The erythrocyte content of the incubation mixtures averaged 0.8%, and did not predict percent CFU-GM survival after the 4-HC incubation. The variability in CFU-GM survival after the purge was less than for previous patients who received buffy-coat cells (with erythrocyte contents ranging from 4-22%) treated with 100 micrograms/ml of 4-HC, indicating that a more uniform purge was achieved. Although the selected dose of 4-HC (60 micrograms/ml) yielded a lower CFU-GM survival, the kinetics of engraftment did not significantly differ between the recipients of light-density or buffy-coat cells. No patient required use of a 'backup' graft because of engraftment failure.

Adolescent↗
PubMed1990

MAO inhibition and clinical response in depressed patients treated with phenelzine.

The authors studied clinical response in 47 depressed inpatients treated with the monoamine oxidase (MAO) inhibitor phenelzine. Improvement on ratings for depression at Week 2 of treatment was correlated with percent MAO inhibition at Week 2 (r = .35, p less than .03), and the modest positive correlation that was found remained after the authors adjusted for the effects of baseline scores on the Hamilton Rating Scale for Depression, dose (mg/kg), and psychosis (partial correlation = .49, p less than .002). Further, the 23 patients ultimately classified as responders had a significantly greater percent MAO inhibition at Week 2 than did the 24 nonresponders (t = 3.02, p less than .005). Thus, the rate of MAO inhibition at Week 2 was significantly correlated with clinical improvement at Week 2 and final response status. These findings could not be explained by other potentially moderating variables such as sex, age, endogenicity, recurrence, and incapacitation.

Adult↗
PubMed1990

The effects of indomethacin on renal function and intracranial hemorrhage in infants with patent ductus arteriosus.

The effects of indomethacin on patent ductus arteriosus (PDA) were retrospectively studied by evaluating 1,600 consecutive infants less than 36 weeks gestation from 1983 to 1986. Two hundred thirteen infants were diagnosed with a PDA, and 102 infants received indomethacin. Indomethacin was associated with successful PDA closure in 81 infants (79%), with 59 infants (58%) closing after a single dose. No cases of renal failure were observed after indomethacin. Nine infants were treated despite a creatinine (Cr) value greater than or equal to 1.5 mg/dl. Cr improved in all these infants after therapy. Blood urea nitrogen values were greater than or equal to 30 mg/dl in 22 infants at the time of treatment; 18 infants (82%) improved. An intracranial hemorrhage (ICH) was detected in 23 infants (22%) by cranial ultrasound prior to indomethacin; there was no progression after treatment. Data suggest that indomethacin is highly associated with closure of a PDA, and therapy did not result in prolonged renal dysfunction or worsening ICH.

Acute Kidney Injury↗
PubMed1990

Dose-dependent platelet stimulation and inhibition induced by anti-PIA1 IgG.

The PIA1 antibody produces several clinically distinct and severe thrombocytopenias. Investigations have demonstrated divergent effects on platelet function; prior reports demonstrated inhibition, while a conflicting publication showed platelet activation. We have resolved this conflict using anti-PIA1 IgG produced by a patient with posttransfusion purpura. Relatively low concentrations stimulated platelet aggregation and release of adenosine triphosphate (ATP) whereas high concentrations inhibited platelet function, producing a thrombasthenia-like state. The number of molecules of platelet-associated IgG necessary to initiate aggregation and ATP release (2,086 +/- 556) or produce maximum aggregation (23,420 +/- 3,706) or complete inhibition (63,582 +/- 2654) were measured with a quantitative radiometric assay for bound anti-PIA1. Preincubation of platelets with high concentrations of PIA1 antibody inhibited platelet aggregation with 10 mumol/L adenosine diphosphate and blocked 125I-labeled fibrinogen platelet binding. Platelet activation with nonfibrinogen dependent agonist, 1 U/ml thrombin, was not inhibited by this high concentration of PIA1 IgG. In conclusion, anti-PIAI IgG produces (1) stimulation of platelet aggregation and ATP release that is initiated with 2000 molecules IgG per platelet and is associated with an increase of 125I-fibrinogen binding; (2) conversely, inhibition of platelet aggregation is observed with maximum antibody binding, 63,000 molecules IgG per platelet, and is mediated via a blockade of fibrinogen binding.

Adenosine Triphosphate↗
PubMed1990

Semipermeable dressing and transepidermal water loss in premature infants.

Within the first days of life, 10 infants, of 32 weeks' gestational age or less, began 2 weeks of treatment with a semipermeable wound dressing over a small area of skin. The effects of the dressing on transepidermal water loss and cutaneous microflora were evaluated. Transepidermal water loss from the semipermeable dressing-treated skin was significantly less than that from the untreated skin immediately after placement of the dressing (8.1 +/- 1.8 g/m2.h-1 vs 17.7 +/- 3.5 g/m2.h-1, P less than .0001). The normal accelerated skin maturation process that occurs in these infants continued beneath the semipermeable dressing. The number of gram-negative bacilli or other bacteria did not increase beneath the semipermeable dressing beyond that seen on the untreated site. Malassezia furfur was found only on the control site, never beneath the semipermeable dressing. According to results of this preliminary study, a semipermeable dressing can be safely used in premature infants and the use of a semipermeable dressing may decrease the excessive transepidermal water loss associated with prematurity.

Bacteria↗
PubMed1989

Thermal stability and folding of type IV procollagen and effect of peptidyl-prolyl cis-trans-isomerase on the folding of the triple helix.

Intact, monomeric type IV procollagen was isolated from the medium of PF-HR9 cells. Its stability was measured by optical rotatory dispersion, differential scanning calorimetry, and trypsin susceptibility of the partially unfolded molecules. At neutral pH, a complex transition between 35 and 42 degrees C and a smaller transition at 48 degrees C are observed by optical rotatory dispersion, using a heating rate of 10 degrees C/h. Reduction of the heating rate to 1.6 degrees C/h resulted in a 1 degree C lowering of the apparent melting temperatures. A similar curve is observed in 10 mM acetic acid, with transitions about 2 degrees C lower. Differential scanning calorimetry revealed transitions at 36.0, 42.1, and 48.0 degrees C at neutral pH, with a total transition enthalpy of 17.1 kJ/mol tripeptide units. In 10 mM acetic acid, transitions at 35.6, 38.9, 41.7, and 50.0 degrees C are observed. The transition enthalpy is 16.4 kJ/mol tripeptide units. The transition enthalpy is similar to values found for interstitial collagens. Results from trypsin digestion experiments are consistent with the stability found by optical methods and calorimetry. The rate and completeness of refolding after melting were measured. In neutral buffer, the initial rate was found to be 0.041 min-1, faster than the refolding rates observed with types pN III and III collagen. Peptidyl prolyl cis-trans-isomerase increased the refolding rate to 0.083 min-1, indicating that cis-trans-isomerization is the rate-limiting step, despite the interruptions in the triple helix. Trypsin digestion experiments indicated that the refolding mechanism is similar in the presence and absence of the enzyme. Refolding was nearly complete in neutral buffer. In 10 mM acetic acid, folding was considerably slower and went to about 74% completion. In both solvents, the refolded material was only slightly less stable than the native material. Electron microscopy of partially refolded samples showed that most refolding started at the COOH terminus, but some was initiated at other sites.

Amino Acid Isomerases↗