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Biomedical subjects

D Watson

Publications and source records attributed to D Watson.

At least 55 records · Page 3Linked to original sources
PubMed1995

Bronchiolitis obliterans organizing pneumonia cured by standard dose inhaled triamcinolone: the first documented case.

Bronchiolitis obliterans organizing pneumonia (BOOP) is characterized clinically by progressive cough, fever, and dyspnea and pathologically by plugging of the bronchiolar and alveolar lumen with buds of loose connective tissue containing fibroblasts and inflammatory cells. The radiographic appearance of the disease varies. Definitive diagnosis requires the histologic identification of the disease in the appropriate clinical setting. Tissue may be obtained by bronchoscopy, needle biopsy, or open lung biopsy. BOOP is responsive to oral corticosteroids, which are the mainstay of therapy. We report the case of a 30-year-old white woman who had BOOP diagnosed in 1991 after extensive therapy for stage II nodular sclerosis Hodgkin's disease. Appropriate treatment of this patient would have been oral corticosteroids for 6 to 12 months, but the patient refused because of a history of significant steroid side effects. Inhaled triamcinolone (3 puffs 4 times per day by metered dose inhaler) for 8 months resulted in complete resolution of the disease. We believe this is the first documented case of clinical and histopathologically confirmed BOOP cured with inhaled corticosteroids.

Administration, Inhalation↗
PubMed1995

Molecular characterization of two monoclonal antibodies specific for the LDL receptor-binding site of human apolipoprotein E.

Apolipoprotein E (apoE), a 299 amino acid protein, is a ligand for the low density lipoprotein receptor (LDLr). It has been established that basic amino acids situated between apoE residues 136 and 150 participate in the interaction of apoE with the LDLr. Evidence suggests that apoE is heterogeneous on lipoproteins in its conformation and in its ability to react with cell surface receptors. Our goal was to produce mAbs that could serve as conformational probes of the LDLr binding site of apoE. We used a series of apoE variants that have amino acid substitutions at residues 136, 140, 143, 144, 145, 150, 152, and 158 to identify the epitopes of two anti-human apoE monoclonal antibodies (mAbs), 1D7 and 2E8, that inhibit apoE-mediated binding to the LDLr. We show that most of the variants that have reduced reactivity with the LDL receptor also have reduced reactivity with the mAbs. The epitopes for both mAbs appear to include residues 143 through 150 and thus coincide with the LDLr-binding site of apoE. It is notable that mAb 2E8, but not 1D7, resembles the LDLr in showing a reduced reactivity with apoE (Arg158 --> Cys). While most of the receptor-defective variants involve replacement of apoE residues directly implicated in binding, substitution of Arg158 by Cys is thought to indirectly affect binding of apoE to the LDLr by altering the conformation of the receptor-binding site. To determine whether the similarity in specificities of the mAbs and the LDLr reflect structural similarities, we cloned and characterized the cDNAs encoding the light and heavy chains of both mAbs. Primary sequence analysis revealed that, although these two antibodies react with overlapping epitopes, their respective complementarity determining regions (CDRs) share little homology, especially those of their heavy chains. The two mAbs, therefore, likely recognize different epitopes or topologies within a limited surface of the apoE molecule. Four negatively charged amino acids were present in the second CDR of the 2E8 heavy chain that could be approximately aligned with acidic amino acids within the consensus sequence of the LDLr ligand-binding domain. This could indicate that mAb 2E8 and the LDLr use a common mode of interaction with apoE.

Amino Acid Sequence↗
PubMed1994

Elevation of systemic oxygen delivery in the treatment of critically ill patients.

BACKGROUND: Elevation of systemic oxygen delivery and consumption has been associated with an improved outcome in critically ill patients. We conducted a randomized trial to determine whether boosting oxygen delivery by infusing the inotropic agent dobutamine would improve the outcome in a diverse group of such patients. METHODS: On the basis of previously published recommendations, we established the following goals: a cardiac index above 4.5 liters per minute per square meter of body-surface area, oxygen delivery above 600 ml per minute per square meter, and oxygen consumption above 170 ml per minute per square meter. If these goals were not achieved with volume expansion alone, patients were randomly assigned to a treatment or control group. The treatment group received intravenous dobutamine (5 to 200 micrograms per kilogram of body weight per minute) until all three goals had been achieved. Dobutamine was administered to the control group only if the cardiac index was below 2.8 liters per minute per square meter. RESULTS: A total of 109 patients were studied. In nine patients the therapeutic goals were achieved with volume expansion alone; all nine patients survived to leave the hospital. Fifty patients were randomly assigned to the treatment group, and 50 to the control group. During treatment, there were no differences between the two groups in mean arterial pressure or oxygen consumption, despite a significantly higher cardiac index and level of oxygen delivery in the treatment group (P < 0.05). Although the predicted risk of death during hospitalization was 34 percent for both groups, the in-hospital mortality was lower in the control group (34 percent) than in the treatment group (54 percent) (P = 0.04; 95 percent confidence interval, 0.9 to 39.1 percent). CONCLUSIONS: The use of dobutamine to boost the cardiac index and systemic oxygen delivery failed to improve the outcome in this heterogeneous group of critically ill patients. Contrary to what might have been expected, our results suggest that in some cases aggressive efforts to increase oxygen consumption may have been detrimental.

Adult↗
PubMed1994

Changes in circulating plasma met-enkephalin concentrations in feline intestinal ischemia--reperfusion.

Plasma met-enkephalin-like immunoreactivity (MLI) levels were determined in cats before, during and after 90 min of intestinal ischemia followed by reperfusion and compared with the levels in control cats. Blood pressure and heart rate were registered and small intestinal mucosal lesions were graded. In control animals, the circulation was stable and there were no mucosal injuries. In the shock group, blood pressure decreased, heart rate increased and severe mucosal lesions were found. The circulating MLI levels were significantly higher 30 min after reperfusion of the ischemic intestine in the shock group than in the control group. There were correlations between MLI and tachycardia and hypotension respectively. Met-enkephalin was released in shock animals after reperfusion of the ischemic intestine and may explain naloxone responsiveness in intestinal shock models.

Animals↗
PubMed1994

The impact of the medical model on nursing practice and assessment.

In its extreme form, the medical model with its concerns of diagnosis, treatment and cure, has been criticized for the narrow and unsatisfactory view it takes of health care. Proponents of nursing theory, in contrast, attempt to develop a conceptual structure which offers a more humanistic approach to patient care, where nurses attempt to move beyond the influences of medical values in the way that they work. This study indicates, however, that the medical model is occasionally compatible with nurses' values, and in certain settings can enhance and support nursing care. In other settings, however, the medical model, although in accord with nursing values, has little to offer practice, and indeed may have a negative effect on the development of alternative approaches to care.

Activities of Daily Living↗
PubMed1994

Pharmacokinetic study of 5-fluorouracil in a novel dialysate solution: a long-term intraperitoneal treatment approach for advanced colorectal carcinoma.

Five patients with advanced colorectal and gastric carcinoma with peritoneal deposits were treated by continuous weekdays intraperitoneal (i.p.) instillation of 5-fluorouracil (5-FU) 200 mg m-2 day-1 in a novel dialysate solution that ensures maximal exposure of peritoneal areas liable to bear tumours for 24 h. A solution of icodextrin, a glucose polymer, in a 21 twin-bag delivery system allowed a single daily exchange and demonstrated the feasibility of long-term continuous ambulatory treatment with up to 17.4 g of 5-FU, delivered intraperitoneally, in this initial study. During the entire study, there were 235 fluid exchanges or 470 connections and disconnections and no bacterial peritonitis or exit site infection were observed. There was no treatment-associated toxicity worse than WHO grade 2. Drug concentrations in both peritoneal and plasma compartments followed a first-order model with similar half-life value of 1.3 h. 5-FU pharmacokinetic parameters (half-life values, total body clearance, peritoneal clearance and pharmacological advantage of the i.p. route) with this novel icodextrin carrier solution were similar to those obtained in other referenced pharmacokinetic studies with other carrier solutions (dextrose dialysate and lactated Ringer's solutions). This confirms that icodextrin solution is physiologically neutral, drug compatible and allows adequate dwell times with constant fluid balance for long-term continuous intraperitoneal chemotherapy. The pharmacokinetic parameters from this study will be used to design a loading dose infusion schedule in an attempt to maintain steady-state i.p. 5-FU levels in a new multicentre phase I trial.

Colorectal Neoplasms↗
PubMed1994

Lipid peroxidation in rats chronically fed ethanol.

Chronic alcohol consumption induces cytochrome P450IIE1, enabling habitual abusers to consume far greater quantities of alcohol than normal subjects. This pathway of metabolism leads to the production of free radical species, which cause tissue damage through peroxidation of cell membranes. Groups of Wistar rats of equal male: female ratio (n = 24) were fed alcohol by gavage twice daily to achieve a dosage of 15 g/kg body weight. Mean peak blood alcohol concentrations of 186 mg% were produced in males and 156 mg% in females. The animals were allowed free access to standard laboratory chow and water. Control animals were pair-fed to the alcoholic group and fed isocaloric glucose by gavage. Groups of animals were killed between 9 and 11 am on consecutive mornings, after nocturnal feeding, since it has previously been shown that fasting rapidly depletes hepatic glutathione concentrations. Hepatic glutathione was measured by a spectrophotometric enzymatic recycling procedure. As a marker of lipid peroxidation hepatic malonaldehyde (MDA) was measured by high performance liquid chromatography. Hepatic MDA was increased in the alcoholic group (p < 0.001), as was total hepatic glutathione (p < 0.0001). Plasma concentrations of alpha-tocopherol were increased in the alcoholic group, but ascorbic acid and superoxide dismutase values were not affected. No sex differences were detected. The increased MDA production in the alcohol group is strong evidence that lipid peroxidation is a mechanism of alcoholic tissue damage. The rise in hepatic glutathione may be an adaptive response to free radical production that protects the rat against tissue damage.

Animals↗
PubMed1994

Effects of RLN and SLN stimulation on glottal area.

In vivo canine experiments have demonstrated that vocal fold stiffness varies proportionately with changing levels of recurrent laryngeal nerve (RLN) and superior laryngeal nerve (SLN) stimulation. This study evaluated the morphologic changes in the glottis at varying levels of nerve stimulation and the presumed effects on laryngeal air particle velocity. Stroboscopic data from the in vivo canine model of phonation were examined under varying conditions of RLN and SLN stimulation. Computerized analysis of stroboscopic images was used to reconstruct the glottal area vs. time waveforms. As RLN stimulation increased, glottal area per cycle decreased (p < 0.05). However, as SLN stimulation increased, glottal area per cycle increased (p < 0.05). However, as SLN stimulation increased, glottal area per cycle increased (p < 0.05). These results support the hypothesis that increasing RLN stimulation at similar levels of SLN stimulation produces an increase in air particle velocity, whereas an increase in SLN stimulation causes a decrease in air particle velocity.

Airway Resistance↗
PubMed1994

Temperament, personality, and the mood and anxiety disorders.

Literature on temperament, personality, and mood and anxiety disorders is reviewed. The review is organized primarily around L. A. Clark and D. Watson's (1991b) tripartite model for these disorders, but other influential approaches are also examined. Negative affectivity (or neuroticism) appears to be a vulnerability factor for the development of anxiety and depression, indicates poor prognosis, and is itself affected by the experience of disorder. Positive affectivity (or extraversion) is related more specifically to depression, may be a risk factor for its development, suggests poor prognosis, and also may be affected by the experience of disorder. Other personality dimensions (e.g., anxiety sensitivity, attributional style, sociotropy or dependence, autonomy or self-criticism, and constraint) may constitute specific vulnerability factors for particular disorders. More longitudinal and measurement-based research that jointly examines anxiety and depression is needed.

Anxiety Disorders↗
PubMed1994

Structures of personality and their relevance to psychopathology.

Trait concepts are used extensively in psychopathology research, but much of this research has failed to consider recent advances in the dimensional structure of personality. Many investigators have discounted the importance of this structural research, arguing that (a) little progress has been made in this area, (b) structural models have little direct relevance for psychopathology research, and (c) the principal methodological tool of structural research--factor analysis--is too subjective to yield psychologically meaningful results. We dispute each of these objections. Specifically, we offer an integrative hierarchical model--composed of four higher order traits--that is congruent with each of the major structural subtraditions within personality. We also discuss the implications of this integrative scheme for basic trait research, for the conceptualization and assessment of psychopathology, and for the etiology of disorder.

Factor Analysis, Statistical↗
PubMed1993

Synthesis and characterization of fluorescent neutral lipid analogs containing N-(7-nitro-2,1,3-benzoxadiazol-4-yl)-aminohexanoic acid.

The synthesis, identification and characterization of neutral lipid analogs containing N-(7-nitro-2,1,3-benzoxadiazoi-4-yl)-aminocaproic acid are reported. The acyl-imidazole derivative of the fluorescent fatty acid was used to esterify L-alpha-glycerophosphorylcholine. Fluorescent phosphatidylcholines were converted to the corresponding diacylglycerols by phospholipase C digestion. Triacylglycerols were formed by esterification with either fluorescent fatty acid-imidazole or non-fluorescent fatty acid anhydride. The 11 compounds synthesized were identified by a combination of thin layer chromatography, liquid secondary ion mass spectrometry and enzymatic digestion. A solvent system for identifying all eleven analogs by thin layer chromatography is presented. The fluorescence characteristics of these analogs are consistent with previously observed parameters of NBD-lipid analogs, including the density-dependent quenching of analogs containing multiple NBD fluorophores. These analogs mimic native lipids, as evidenced by digestions with the enzymes, porcine pancreatic lipase, phospholipase C and phospholipase A2.

4-Chloro-7-nitrobenzofurazan↗
PubMed1993

Hyaluronidase.

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Anesthesia, Local↗
PubMed1993

Postnatal growth in infants born between 700 and 1,500 g.

Our purpose was to examine postnatal growth in very low birth weight (VLBW) infants (n = 54). A high frequency of intrauterine growth retardation was noted that was corrected by plotting birth weight against crown-heel length and not gestational age. No differences in postnatal growth were noted between infants whose size was appropriate for gestational age (n = 37) and those small for gestational age (n = 17). Overall, growth tended to exceed that previously published. Weight but not length or head gain was less in the smaller (< or = 1,000 g) when compared to the larger (> 1,000 g) VLBW infant. Poorer weight gain could not be related to more "illness" or less nutrient intake in the smaller infants.

Aging↗
PubMed1993

Testing of Streptococcus pneumoniae for resistance to penicillin.

The increasing prevalence of penicillin-resistant Streptococcus pneumoniae requires antibiotic susceptibility tests that can be done with greater ease and reliability. We measured the MIC of penicillin for pneumococci by the tube macrodilution method with Mueller-Hinton broth (MHB), Haemophilus Test Medium (HTM), Todd-Hewitt broth with 0.5% yeast extract (THY), and MHB with 3% lysed horse blood (LHB). Eight (19%) and 6 (14%) of 42 pneumococcal isolates failed to generate turbid growth in MHB and HTM, respectively, whereas all pneumococcal isolates did so in THY and LHB. For those strains that replicated to turbidity, the mean MICs of penicillin were lower in MHB and HTM than in THY and LHB, with differences being significant (P < 0.05) for comparisons with LHB. Four isolates appeared to be penicillin susceptible in HTM but were actually moderately resistant in THY and LHB, and two isolates appeared to be moderately resistant but were resistant. A similar failure to detect resistance was seen with MHB. S. pneumoniae ATCC 49619, a moderately penicillin-resistant strain that has been proposed for quality control testing, gave variable results in MHB or THM and appeared to be susceptible to penicillin in some assays, whereas the MICs for S. pneumoniae ATCC 49619 in THY or LHB fell within a twofold dilution range, with geometric means of 0.16 and 0.18 micrograms/ml, respectively. Pneumococcal isolates thus may appear falsely susceptible to penicillin when tested in MHB or HTM. LHB remains the standard medium; however, because THY is an easily prepared clear medium that can be used in automated systems and appears to yield results similar to those obtained with LHB, THY deserves consideration for routine use.

Culture Media↗