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J M Davis

Publications and source records attributed to J M Davis.

At least 163 records · Page 9Linked to original sources
PubMed1996

Prediction of haloperidol steady-state levels in plasma after a single test dose.

Because of large interindividual variabilities in the pharmacokinetics of haloperidol (HPDL), empirically adjusting the dose to achieve steady-state levels in plasma (Css) is a time-consuming process. We report a method to individualize dose to achieve a desired Css from an observed drug level 24 hours after a single 15-mg test dose of HPDL. Drug-free schizophrenic and schizo-affective patients were blindly and randomly assigned to achieve a low (< 5 ng/ml), medium (10-18 ng/ml), or high (> 25 ng/ml) Css range of HPDL. On day 1 of the study, each patient received an oral "test" dose of HPDL (15 mg), and blood was drawn 24 hours later to determine drug levels in plasma (C24h). The first 34 patients (group I) were then maintained empirically on 2, 5 to 8, or 10 to 15 mg twice daily of oral HPDL concentrate for 5 days to achieve a low, medium, or high Css range, respectively. For the next 58 patients (group II), the dose of HPDL to achieve the assigned Css range was computed by using C24h in a prediction formula. Application of the C24h correctly predicted the maintenance dose required to achieve the Css in 73.2% of the cases. Further, there was a highly significant correlation (R2 = 0.877, p < 0.0001) between the predicted dose and the actual dose required to achieve the targeted Css range. On the basis of these results, we have formulated a nomogram to help predict the maintenance dose required to achieve low, medium, or high HPDL targeted ranges at various C24h values.

Adult↗
PubMed1996

Antipsychotic dosing strategies in acute schizophrenia.

Determining the optimal dose of antipsychotic for an acute schizophrenic episode has been an elusive goal. Empirical dose adjustment with conventional neuroleptics has generally led to excessive drug exposure, in part due to the lag time between initiation of therapy and response and in part due to the indefinite nature of the response. Data from dose- and plasma concentration-response studies and from imaging studies have provided some guidance. In particular, newer antipsychotic drugs such as risperidone and sertindole have been evaluated in multiple fixed-dose designs to determine the optimal dose or dose range. To devise an overall treatment strategy for an acute psychotic episode, we reviewed and incorporated data from a number of controlled studies.

Acute Disease↗
PubMed1996

Localization and activity of recombinant human CuZn superoxide dismutase after intratracheal administration.

Hyperoxia and mechanical ventilation cause acute lung injury which may be mitigated by prophylactic intratracheal (IT) administration of recombinant human CuZn superoxide dismutase (rhSOD). However, little is known about the localization, activity, and metabolism of rhSOD after IT administration by instillation or nebulization. Twenty-six newborn piglets were intubated, mechanically ventilated, and given either saline or fluorescently labeled rhSOD (5 mg/kg IT) by instillation or nebulization. Animals were killed 1, 6, or 12 h later. Intact rhSOD (% total fluorescence still associated with macromolecules) and total SOD activity in lung tissue were then determined. Results indicate that, after 1 and 6 h of administration, the majority of rhSOD present in the lung was still associated with the fluorescent label. By 12 h, most of the rhSOD was no longer fluorescently labeled. At 1 h, lung SOD activity increased by 100% compared with untreated control values, with activity remaining elevated at 6 and 12 h. Laser confocal microscopy of lung tissue showed that at 1 h, labeled rhSOD was found throughout the lung, inside a variety of cell types of airways, respiratory bronchioles, and alveoli. Deposition was more homogeneous after nebulization. Negative controls had minimal background fluorescence. These data indicate that after IT administration, rhSOD is rapidly incorporated into cells in the lung and significantly increases lung SOD activity. These observations have important implications for the clinical use of rhSOD in human trials.

Animals↗
PubMed1996

Ultrasonic nebulized in comparison with instilled surfactant treatment of preterm lambs.

To evaluate the efficiency and distribution of ultrasonic nebulized versus instilled surfactant in the treatment of surfactant deficiency at varying degrees of maturation, twin or triplet lamb fetuses were delivered at 125 to 137 d gestational age and received nebulized natural surfactant (Neb Only), instilled surfactant followed by a second instilled dose (Inst/Inst), instilled surfactant followed by nebulized surfactant (Inst/Neb), or no surfactant (Control). The lambs were ventilated for 6 h. Twenty-eight lambs were categorized into two groups (low compliance versus moderate compliance) based on initial physiologic lung characteristics. Efficiency of deposition of nebulized surfactant directly correlated with the compliances and ventilatory efficiency indices measured at 15 min of age. The low-compliance group (Low Comp) had significantly lower efficiency of surfactant deposition (7.6 +/- 1.6%) than did the moderate-compliance group (Mod Comp) (23.4 +/- 2.5%) (p < 0.01). Overall, instilled surfactant had a reasonably homogeneous distribution, whereas nebulized surfactant had a less homogeneous distribution, except for the Low Comp, Inst/Neb group, which had a distribution pattern similar to that for instilled surfactant. The potential for nebulized surfactant therapy for respiratory distress syndrome (RDS) may be limited by the nonhomogeneous nature of ventilation in the preterm lung.

Administration, Inhalation↗
PubMed1996

Relation of serum valproate concentration to response in mania.

OBJECTIVE: This study was designed to determine the relation of valproate serum levels to clinical improvement and development of adverse effects in hospitalized patients with acute mania. The initial fixed-dose escalation design, the monotherapy with divalproex, and the control of variables that is possible only with hospitalized patients reduced the confounding factors present in most outpatient studies of serum level-response relationships. METHOD: Sixty-five hospitalized patients who met the Research Diagnostic Criteria for bipolar disorder with mania were treated with divalproex, 750 mg/day for 2 days and then 1,000 mg/day on days 3-5; the dosage was subsequently adjusted as clinically indicated for the remainder of the 21-day study. Manic symptoms were assessed with the Mania Rating Scale, which is derived from the Schedule for Affective Disorders and Schizophrenia. RESULTS: At day 5, patients with serum valproate levels > or = 45 micrograms/ml were two to seven times as likely as patients with levels < 45 micrograms/ml to show 20% or greater improvement in scores on the manic syndrome subscale, the behavior and ideation subscale, elevated mood, increased activity, motor hyperactivity, and psychosis. Endpoint analyses yielded similar results. Adverse experiences characteristic of divalproex treatment were disproportionately associated with serum levels > or = 125 micrograms/ml. CONCLUSIONS: Acutely manic patients treated with divalproex who have valproate serum levels between 45 and 100-125 micrograms/ml are much more likely to have efficacious and well-tolerated responses than patients with lower or higher levels of valproate.

Acute Disease↗
PubMed1996

Similar breast cancer cell contamination of single-day peripheral-blood progenitor-cell collections obtained after priming with hematopoietic growth factor alone or after cyclophosphamide followed by growth factor.

PURPOSE: To evaluate tumor-cell contamination of peripheral-blood progenitor-cell (PBPC) collections obtained after priming with granulocyte colony-stimulating factor (G-CSF). PATIENTS AND METHODS: Immunocytochemical (ICC) and tumor clonogenic (TCA) assays were used to analyze tumor-cell contamination of pretreatment peripheral-blood (PB) and bone marrow (BM) samples, and of PBPC collection samples obtained after priming with G-CSF 5 micrograms/kg/d for 5 or 7 days in 38 women with advanced breast cancer undergoing high-dose chemotherapy (HDC). Results were compared with 37 historical control patients who underwent PBPC mobilization with cyclophosphamide (4 g/m2) followed by granulocyte-macrophage colony-stimulating factor (GM-CSF) 5 micrograms/kg/d for 14 days. RESULTS: Before PBPC priming with G-CSF, only one of 37 (3%) PB and four of 36 (11%) BM samples had tumor cells detected by ICC. Tumor-cell contamination of PBPC collections obtained after 5 or 7 days of G-CSF priming was observed in only three of 38 patients (8%). All patients with tumor cells detected in the PBPC collection had stage IV disease. Cells with in vitro clonogenic potential were detected only in the pretreatment BM sample in one patient, and another two patients had ICC- and TCA-positive PBPC samples despite tumor-negative PB and BM before priming. These results are similar to those previously reported for PBPC primed with cyclophosphamide and GM-CSF. CONCLUSION: In patients with advanced breast cancer responsive to cytotoxic chemotherapy, tumor-cell contamination is not increased in PBPC collected after 5 or 7 days priming with G-CSF and appears similar to that seen when PBPC are primed with cyclophosphamide followed by GM-CSF.

Adult↗
PubMed1996

Safety and pharmacokinetics of recombinant human superoxide dismutase administered intratracheally to premature neonates with respiratory distress syndrome.

OBJECTIVE: As a first step in the evaluation of recombinant human CuZn superoxide dismutase (rhSOD) in the prevention of neonatal lung injury, safety and pharmacokinetics of intratracheally (IT) administered rhSOD were studied. METHODS: Twenty-six preterm infants weighing 750 to 1250 g with respiratory distress syndrome were studied in three sequential groups (placebo, 0.5, and 5 mg/kg). Placebo or rhSOD was administered IT 30 minutes after the first surfactant dose. Serial blood and urine studies, rhSOD levels, tracheal aspirate fluid (TAF) markers of acute inflammation, radiographs, and ultrasounds were performed over the 28-day study period. RESULTS: Serum SOD concentrations were similar at baseline for all three groups (geometric mean 0.2, upper-lower limit 0.1 to 0.2 microgram/mL). In the 0.5-mg/kg group, levels were highest at 12 hours (geometric mean 0.7, upper-lower limit 0.5 to 0.8 microgram/mL) and returned to baseline by day 3. In the 5-mg/kg group, levels were highest at 6 hours (geometric mean 3.0, upper-lower limit 2.3 to 4.0 micrograms/mL) and returned to baseline by day 4. Concentrations of SOD in TAF were also similar at baseline for all three groups (geometric mean 0.2, upper-lower limit 0.2 to 0.3 microgram/mL). There were no significant increases in the placebo group, but levels in the 0.5-mg/kg group were highest when first sampled at 24 hours (geometric mean 1.1, upper-lower limit 0.8 to 1.4 micrograms/mL) and returned to baseline by day 3. In the 5-mg/kg group, levels were also highest when sampled at 24 hours (geometric mean 1.4, upper-lower limit 0.9 to 2.1 micrograms/mL) and returned to baseline by day 4. Urine levels were highest at 12 hours in both the 0.5-mg/kg (geometric mean 1.3, upper-lower limit 1.0 to 1.7 micrograms/mL) and 5-mg/kg infants (geometric mean 6.4, upper-lower limit 3.9 to 10.4 micrograms/mL) and decreased significantly by day 2 to 3. rhSOD activity assays (serum, TAF, and urine) demonstrated that the enzyme still possessed significant activity. No adverse effects of rhSOD were found. TAF neutrophil chemotactic activity and albumin concentrations, important acute lung injury markers, were significantly lower in the high-dose rhSOD group compared with the other groups. CONCLUSIONS: Data suggest that a single IT dose of rhSOD results in significant increases in both concentration and activity of the antioxidant in serum, TAF, and urine for 2 to 3 days. The enzyme appears to be well tolerated, and TAF inflammatory markers are reduced after administration. This has important implications in rhSOD trials to prevent acute and chronic lung injury in preterm neonates.

Drug Monitoring↗
PubMed1996

The thrombin inhibitor, hirudin, attenuates lipopolysaccharide-induced liver injury in the rat.

The administration of gram-negative bacterial lipopolysaccharide (LPS) to rats results in hepatic parenchymal cell injury within 6 hr. The coagulation system is critical to the pathogenesis, but previously reported results suggested that its critical role is independent of insoluble clot formation and that thrombin may be a key mediator of liver injury. To test the hypothesis that thrombin is involved in LPS-induced liver injury, animals were treated with the selective thrombin inhibitor, hirudin. The hirudin treatment regimen effectively inhibited thrombin, as evidenced by prolonged activated partial thromboplastin time and by maintenance of plasma fibrinogen concentrations in LPS-treated rats. Treatment with hirudin prevented LPS-induced liver injury, assessed by plasma alanine aminotransferase activity and histological evidence of hepatocellular necrosis. Previous studies have shown that LPS exposure results in the accumulation of neutrophils and platelets within the liver and that both of these cell types are critical for the development of LPS-induced liver injury. Hirudin attenuated in part the decrease in blood platelet concentration that accompanied LPS administration, but did not alter hepatic platelet or neutrophil accumulation. These results support the hypothesis that thrombin is required for hepatic injury from LPS exposure, but that it does not act by promoting the accumulation of platelets or neutrophils within the liver.

Animals↗
PubMed1996

Carl Friedrich Wilhelm Ludwig: the founder of modern renal physiology.

The revolutionary "Zeitgeist" in the Europe of the 1840s left its mark no less in science than it did in the social and political life of the population. The essence of the scientific revolution was the change in paradigm from a vitalist-inductive to a mechanistic hypothetico-deductive approach, in which the experiment assumed the central role. The initiator of this new approach was a young physiologist in Marburg, Germany-Carl Friedrich Wilhelm Ludwig- and the first document his 1842 Habilitation thesis. Although this thesis was limited to a study on renal function, the impact of this epochal new approach, namely the analysis and explanation of living phenomena solely on the basis of physics and chemistry, went far beyond renal physiology: it revolutionised thinking in all the biological sciences. In this thesis, Carl Ludwig enunciated the principle of glomerular ultrafiltration driven by physical forces alone, i.e., the difference in the hydrostatic and oncotic pressures of the blood in the glomerular capillaries, a concept which remains valid today. Ludwig thus became the first scientist to describe correctly a principal component of renal function, the process of glomerular filtration.

Europe↗
PubMed1996

Balloons, beds, and breakdown. Effects of low-air loss therapy on the development of pressure ulcers in cardiovascular surgical patients with intra-aortic balloon pump support.

There is limited research related to pressure ulcers in the ICU patient population and even less has focused on patients who have undergone cardiovascular surgery and IABP support. The objective of this article was to determine the incidence of pressure ulcers in the postoperative CVS patient with IABP support and to determine if LAL therapy was more effective in the prevention of pressure ulcers in this patient population. In a quasiexperimental design, a convenience sample of 36 adults was used. Patients who were placed on IABP support the day of surgery were enrolled into the study within 24 hours of admission to the cardiovascular recovery room. Data collection was daily for 4 days and continued if the patient developed a pressure ulcer. Final measurements were obtained on the day of hospital discharge. Instruments used were demographic data form, APACHE II, Patient Identification for Rotation Therapy, and the Braden Scale. The most common surgical patient in this pilot underwent aortocoronary bypass with IABP support. Pressure ulcers developed in 9 of 36 (25%) patients for a total of 17 ulcers. Patients who developed pressure ulcers were generally older, had a history of cerebrovascular disease, renal insufficiency, a higher APACHE II score, and Braden score of 9 on POD 1. In addition, these patients generally had a lower hemoglobin level, higher serum creatinine level, and an altered level of consciousness on POD 1. The results suggest that LAL therapy does make a difference in the prevention of pressure ulcers in the aortocoronary bypass patient with IABP support.

Aged↗
PubMed1995

April fool.

Explore the source record for details and available documents.

Coriolis Force↗
PubMed1995

Absence of breast cancer cells in a single-day peripheral blood progenitor cell collection after priming with cyclophosphamide and granulocyte-macrophage colony-stimulating factor.

The effect of priming on occult tumor cell involvement of peripheral blood (PB) and PB progenitor cell (PBPC) collections is poorly characterized. Using sensitive immunocytochemistry (ICC) and tumor clonogenic assays (TCA) specific for epithelial-derived tumor cells, hematopoietic specimens were analyzed for PBPC and occult tumor cell involvement in 28 patients with chemotherapy-sensitive stage IIIB or IV breast cancer. Before PBPC priming, tumor was detected by ICC in PB of 1 of 23 (4%) patients and in bone marrow (BM) harvests of 4 of 27 (15%) patients. Fifteen days after cyclophosphamide and granulocyte-macrophage colony-stimulating factor (GM-CSF) priming, 2 of 28 (7%) patients had ICC-positive PBPC collections. The median amplification of CD34+ PBPC during this time was over 19-fold (range, < 1 to 199). One patient had pretreatment tumor involvement of both PB and BM. One patient grew tumor colonies in TCA; the PB and BM were ICC- and TCA-positive, but the PBPC collection was ICC-positive and TCA-negative. After cytoreduction with conventional-dose chemotherapy, patients with advanced breast cancer and histologically negative BM biopsy specimens have rare tumor cell involvement of PB and BM. Despite effective PBPC priming with cyclophosphamide and GM-CSF, clonogenic breast cancer cells were not found in the PBPC collection performed on day 15.

Adult↗
PubMed1995

Fetal alcohol syndrome at the turn of the 20th century. An unexpected explanation of the Kallikak family.

At the turn of the 20th century, studies of a family known in the literature as the Kallikaks were used to document the hereditary nature of mental retardation, poverty, and antisocial behavior. This family was said to authenticate eugenic theory, which states that heritable characteristics carried by individuals on "independent unit characters are unalterable determinants of behavior and performance. A review of the original Kallikak data, however, suggests that in utero exposure to alcohol rather than heredity contributed significantly to the transgenerational learning failure seen throughout the Kallikak pedigree. However, eugenic theory was so thoroughly accepted that the promotion and acceptance of "hereditary feeblemindedness" as the principal cause of the developmental problems in the affected offspring smothered the research efforts on in utero effects of alcohol until long after the eugenic concepts were abandoned later in the century.

Female↗
PubMed1995

Study of high-field dispersion in micellar electrokinetic chromatography.

The anomalous dispersion of hydrophobic, highly retained analytes at high electric field strengths E in micellar electrokinetic chromatography (MEKC) is experimentally and theoretically quantified. A simple model for plate number N is proposed, in which only plug size and longitudinal diffusion govern dispersion. This model describes well the dispersion of acetone, 2'-deoxyadenosine, and 2'-deoxyadenosine-5'-monophosphate (dAMP) in MEKC buffers and also dAMP in capillary-electrophoresis buffers. However, the model describes the dispersion of 1-nitropyrene, pyrene, perylene, and the 4-chloro-7-nitrobenzofuran (NBD) derivative of cyclohexylamine only at low E's; for these analytes, a nonequilibrium-like dispersion causes N to decrease rapidly at high E's. Furthermore, the dispersion of NBD-cyclohexylamine has a dependence on capillary diameter. Theoretical arguments are proposed, which show that this additional dispersion cannot be explained quantitatively by mass-transfer kinetics, micellar polydispersity, hydrodynamic flow, Joule heating, or the radial variation of partition coefficient. In addition, experiments are performed suggesting that wall adsorption and sample inhomogeneity are not responsible for the efficiency loss. Other dispersion sources are suggested for future exploration.

Acetone↗
PubMed1995

The effects of hyperoxia, mechanical ventilation, and dexamethasone on pulmonary antioxidant enzyme activity in the newborn piglet.

It has been previously shown that prophylactic, intravenous dexamethasone (DEX) and intratracheal recombinant human Cu/Zn superoxide dismutase (SOD) ameliorate lung injury in newborn piglets treated with 48 hr of hyperoxia and mechanical ventilation. DEX has many pharmacologic effects, including the possible induction of antioxidant enzyme systems. To investigate whether the effects of DEX are mediated by an increase in endogenous antioxidant enzyme activity, 5 groups of term newborn piglets were studied: Group 1 piglets were ventilated with room air for 48 hr; Group 2 animals were ventilated with 100% O2 for 48 hr; Group 3 animals were ventilated with room air for 48 hr and received DEX (0.7 mg/kg) every 12 h; Group 4 were ventilated with 100% O2 for 48 hr and also received DEX; Group 5 animals were no ventilated and were sacrificed at time 0. At the conclusion of the studies, bronchoalveolar lavage (BAL) was performed and the lungs were removed and homogenized. Lung tissue and BAL were analyzed for SOD, catalase, GPX activities, and total protein concentration. No significant differences in any of these assays were seen in either lung tissue or BAL in the 5 groups. These observations indicate that 48 hr of hyperoxia, mechanical ventilation, or dexamethasone treatment does not induce activity of SOD, catalase, or glutathione peroxidase (GPX) in the lungs of newborn piglets. Thus postnatal DEX appears to minimize neonatal lung injury by mechanisms that are independent of these enzymes.

Analysis of Variance↗