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Biomedical subjects

D L Smith

Publications and source records attributed to D L Smith.

At least 217 records · Page 12Linked to original sources

Effect of inhalation injury, burn size, and age on mortality: a study of 1447 consecutive burn patients.

The relative impact of inhalation injury, burn size, and age on overall outcome following burn injury was examined in 1447 consecutive burn patients over a five and a half year period. The overall mortality for all patients was 9.5% (138 of 1447). The presence of inhalation injury, increasing burn size, and advancing age were all associated with an increased mortality (p < 0.01). The incidence of inhalation injury was 19.6% (284 of 1447) and correlated with increasing percent total body surface area (%TBSA) burn (r = 0.41, p < 0.01) and advancing age (r = 0.15, p < 0.01). The overall mortality for patients with inhalation injury was 31% (88 of 284) compared with 4.3% (50 of 1163) for those without inhalation injury. Using multivariate analysis inhalation injury was found to be an important variable in determining outcome, but the most important factor in predicting mortality was %TBSA burn (accuracy = 92.8%) or a combination of %TBSA burn and patient age (accuracy = 93.0%). Adding inhalation injury only slightly improved the ability to predict mortality (accuracy = 93.3%). The presence of inhalation injury is significantly associated with mortality after thermal injury but adds little to the prediction of mortality using %TBSA and age alone.

Adolescent↗

Tracheobronchomegaly: an unusual presentation of a rare condition.

Tracheobronchomegaly is a rare cause of recurrent chest infections often with persistent, unproductive cough. A case is described which presented as a severe life threatening pneumonia in which the bronchoscopic, radiographic, and computed tomographic findings are given.

Bronchi↗

The chest radiograph in cystic fibrosis: a new scoring system compared with the Chrispin-Norman and Brasfield scores.

BACKGROUND: Scoring systems for the chest radiograph in cystic fibrosis are used to compare patients and different treatment regimens, and to monitor respiratory disease in individual patients. The Northern chest radiograph score was designed to allow one person to assess the radiological features of lung involvement in cystic fibrosis in as simple, rapid and equally reproducible manner as the established Chrispin and Norman, and Brasfield scoring systems. METHODS: Forty five chest radiographs were scored by 10 physicians with a special interest in cystic fibrosis according to the Brasfield and Northern methods, and by five pairs of physicians according to the Chrispin-Norman criteria. Three individuals and two pairs rescored the radiographs after an interval of 3-5 months. The Northern score was performed with and without a lateral view, using the original posteroanterior radiograph. RESULTS: The Northern score showed a better agreement between observers for the ranking of the radiographs. It was equally well related to respiratory function tests, the Shwachman-Kulczycki score of overall clinical status, and in its discrimination between different radiographs as the other two scoring systems. The Northern score performed equally well with or without a lateral film. CONCLUSIONS: The Northern system fulfils the requirements of a chest radiograph score more successfully than the Chrispin-Norman or Brasfield systems, and does not require a lateral film.

Cystic Fibrosis↗

Prophylaxis against infection in total joint arthroplasty. One day of cefuroxime compared with three days of cefazolin.

The efficacy of cefuroxime was compared with the efficacy of cefazolin for prophylaxis against postoperative wound infection in a prospective, double-blind, multicenter study of 1354 patients who had had elective primary or revision total hip or knee arthroplasty. The patients were randomly assigned to receive either 1.5 grams of cefuroxime followed by 750 milligrams eight and sixteen hours later (for a total of one day of antibiotic treatment), or one gram of cefazolin every eight hours for nine doses (for a total of three days of antibiotic treatment). The first dose of each drug was administered fifteen to sixty minutes before the operative incision was made (for a primary operation) or after tissue samples had been obtained for culture (for a revision procedure). After the operation, the patients were assessed daily while hospitalized and then at two to three months and one year after the operation. Demographic characteristics and risk factors were similar in the two groups. For the patients who had had a primary hip arthroplasty, the rate of deep wound infection was 0.5 per cent (one of 187) for those who had received cefuroxime and 1.2 per cent (two of 168) for those who had received cefazolin. For the patients who had had a primary knee arthroplasty, the rate of deep wound infection was 0.6 per cent (one of 178) for those who had received cefuroxime and 1.4 per cent (three of 207) for those who had received cefazolin.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Identification of the major components of the high molecular weight crystallins from old human lenses.

High molecular weight aggregates from the water soluble portion of four lenses from older donors were examined by mass spectrometric techniques that permitted unambiguous identification of the principal components as alpha A-, alpha B- and gamma s-crystallins. Post-translational modifications that were located and identified included deamidations in alpha A and gamma s and an intramolecular disulfide bond in alpha A-crystallin. The C-terminus of alpha A was not found, supporting previous suggestions that this portion of the protein may be important in preventing aggregation.

Aged↗

Prenatal sonographic findings in trisomy 13, 18, 21 and 22. A review of 46 cases.

A study of 46 patients with trisomic fetuses was performed to determine if there are one or more second-trimester ultrasonic findings predictive of aneuploidy. Videotapes of ultrasonography performed prior to amniocentesis on the 46 fetuses with autosomal trisomy and from a control group of 50 chromosomally normal fetuses were reviewed without knowledge of the karyotype. Fetuses with autosomal trisomies had short long bones, especially femurs, as well as high biparietal diameter/femur length ratios. In addition, a nuchal thickness of > 5 mm, abnormal heart anatomy, slight pyelectasis, increased bowel echogenicity and/or abnormal flexion of the hands were all predictive of autosomal trisomies.

Adult↗

Comparison of Irlen scotopic sensitivity syndrome test results to academic and visual performance data.

UNLABELLED: Irlen has defined a condition called Scotopic Sensitivity Syndrome (SSS) that is associated with reading problems. According to Irlen, SSS can be treated by the use of colored filters, but there is disagreement about the existence of SSS and the efficacy of colored filter therapy. METHODS: Thirty-nine children participated in the study: 24 were academically normal, nine had specific reading problems, and six had problems in multiple academic areas. SSS levels and preferred overlay colors were determined. Optometric test data were also available for each subject. RESULTS: No significant relationships were found between academic classification and degree of SSS. There were also no significant relationships between preferred overlay color and any other variables. There was, however, a significant tendency for subjects with higher SSS levels to be candidates for vision therapy and to derive greater benefit from the colored overlays. CONCLUSIONS: Many questions about the use of colored filters for the treatment of reading problems remain unanswered. Among these are questions dealing with whether the M-pathway anomalies found in some dyslexics are also present to a lesser degree in other cases of reading disabilities, and how colored filters could re-balance the M- and P-pathways. Is it the color of the filter itself that is critical, or is it the change in luminance or contrast produced by the filter that seems to make it easier for some subjects to read? More research will be needed to answer these questions.

Child↗

The optometry game: enhancing test selection and lens prescribing skills by use of computer simulations.

The Optometry Game is a computer simulation developed to aid students in practicing test selection and lens prescription skills. Features of the simulation include a game format, digitally reproduced voices and patient pictures, and the ability of the user to customize the game for a variety of applications. Twenty optometry students evaluated the game by playing a variety of simulated patients and found it to be potentially useful in various classroom learning environments.

Computer Simulation↗

Histoplasmosis in Missouri: historical review and current clinical concepts.

Histoplasmosis is particularly common in Missouri, and many important clinical observations about the disease were made in this state in the 1950s and 1960s. When the AIDS epidemic spread to Missouri in the mid-1980s, histoplasmosis became recognized as a common and important opportunistic infection among Missourians with AIDS. Clinicians must maintain a high level of suspicion for histoplasmosis in any HIV-infected patient who presents with unexplained fever, particularly if the patient has evidence of hepatosplenomegaly, generalized lymphadenopathy, pancytopenia, abnormal liver function tests, or bilateral pulmonary infiltrates. The diagnosis of histoplasmosis can be established rapidly by observation of organisms on peripheral blood smear or bone marrow biopsy specimens or by Histoplasma Polysaccharide Antigen testing. The diagnosis can be confirmed by blood cultures in most cases. Histoplasmosis in AIDS is invariably fatal if not treated. Treatment consists of two phases: initial induction therapy and subsequent lifelong maintenance therapy. Amphotericin B and itraconazole are extremely effective for induction and maintenance therapy; fluconazole appears to be effective maintenance therapy. Strategies for the prevention of histoplasmosis in high risk patients are being evaluated currently.

Histoplasmosis↗

Immunocytologic characteristics of mononuclear cell populations found in nonseptic olecranon bursitis.

OBJECTIVE: To determine the immunocytologic characteristics of the various subsets of nonseptic olecranon bursal fluid mononuclear cells. METHODS: Twenty consecutive patients with culture negative olecranon bursitis had immunocytochemical and flow cytometric analysis performed using a panel of monoclonal antibodies to determine lymphocyte and monocyte/macrophage population subtypes and proportions. RESULTS: In traumatic bursitis (n = 9), the mean (+/- SD) white blood cell (WBC) count/mm3 was 1,368 +/- 1,559; WBC mononuclear differential count was 29.5 +/- 19% lymphocytes and 55 +/- 26% monocyte/macrophages. In idiopathic bursitis (n = 11), the mean WBC/mm3 was 376 +/- 515; WBC mononuclear differential count was 28.5 +/- 16% lymphocytes and 52 +/- 27% monocytes/macrophages. Flow cytometry revealed 88% CD2+ T lymphocytes in the lymphocyte population, 3% B lymphocytes and CD4/CD8 T cell mean ratio of 2.5 +/- 1.5 for traumatic bursitis and 88% CD2+ T lymphocytes, 4% B lymphocytes and CD4/Cd8 ratio of 1.4 +/- 0.6 for idiopathic bursitis (p < 0.05, t test). Both groups contained increased proportions of lymphocyte subtypes expressing activation markers: CD25+, CD26+ and HLA DR+ compared to normal peripheral blood. In traumatic bursitis, the mean percent of CD14+ cells (monocyte/macrophages) was 62 +/- 24; in idiopathic bursitis, the mean percent was 51 +/- 28. The vast majority expressed high levels of HLA-DR indicating activation. CONCLUSION: We observed a preponderance of activated T cell subpopulations and monocyte/macrophages suggesting an immunologic role for these cell populations in the development and perpetuation of nonseptic bursitis.

Adult↗

Membrane topology of a P-type ATPase. The MgtB magnesium transport protein of Salmonella typhimurium.

P-type ATPases are a family of cation transport enzymes present in all species from bacteria to mammals whose members mediate membrane flux of all common biologically relevant cations. More than 50 members of this family of transporters have been sequenced; extensive structural data are available, and several members have been analyzed by site-directed mutagenesis. Nonetheless, there is no current consensus regarding their membrane topology. In this work, the Salmonella typhimurium Mg2+ transporting P-type ATPase encoded by the MgtB locus has been used as a model for P-type ATPases. Unlike other prokaryotic P-type ATPases, the MgtB protein is similar in length, amino acid sequence, and hydropathy profile to known eukaryotic P-type ATPases. The membrane topology of MgtB was analyzed by several epitope insertions in MgtB and from the activity of 35 protein fusions between MgtB and the reporter enzymes BlaM (beta-lactamase) and LacZ (beta-galactosidase). The epitope insertions within MgtB all retained function as assessed by cation uptake assays and were regulated normally by the level of Mg2+ within the growth medium. The epitope insertion and fusion protein data are completely incompatible with the numerous previously proposed models for P-type ATPases predicting 7, 8, 9, or 12 transmembrane segments. Rather, they indicate that MgtB contains 10 transmembrane segments with both amino and carboxyl termini residing within the cytosol. By extension, we suggest that all eukaryotic P-type ATPases contain 10 transmembrane segments with both termini within the cytosol.

Adenosine Triphosphatases↗

Reliability of histologic scoring for lupus nephritis: a community-based evaluation.

OBJECTIVE: To determine the reliability of the National Institutes of Health (NIH)-modified semiquantitative histologic scoring system for lupus nephritis. DESIGN: Cross-sectional study, repeated after 8 to 9 months. SETTING: Four community hospitals and one university medical center. PARTICIPANTS: Five pathologists, all experienced in reading renal biopsy specimens, assessed 25 specimens that had been obtained from patients with a clinical diagnosis of systemic lupus erythematosus and showed diffuse proliferative glomerulonephritis. MEASUREMENTS: Biopsy specimens were scored independently and blindly by pathologists for components of nephritis chronicity and activity. Reliability was measured by percentage agreement, intraclass correlation coefficient or kappa statistic, and individual reader effect on the group arithmetic mean. RESULTS: As scored by the readers, the mean chronicity index score varied from 2.3 to 4.8 on a 12-point scale (P = 0.001) and the mean activity index score varied from 5.8 to 11.4 on a 24-point scale (P = 0.0001). Pairs of readers gave scores within 1 point for the chronicity index and within 2 points for the activity index in 50% of cases, and risk group assignments based on chronicity index (three strata) and activity index (two strata) were concordant in 59% and 76% of cases, respectively. Intraclass correlation coefficients for inter-reader agreement were 0.58 for the chronicity index (P < 0.01) and 0.52 for the activity index (P < 0.01). Intrareader agreement was uniformly higher than inter-reader agreement, but mean intraclass correlation coefficients exceeded 0.70 for only 1 of the 10 index components. Repeated readings yielded chronicity index scores that were more than 1 point discordant in 45% of cases and activity index scores that were more than 2 points discordant in 43% of cases. Risk group assignment changed on the basis of chronicity index and activity index in 36% and 21% of cases, respectively. CONCLUSIONS: In a nonreferral setting, the NIH-modified scoring system for lupus nephritis is only moderately reproducible and, if used to prognosticate renal outcome, may result in erroneous predictions of risk for renal failure and response to therapy.

Chronic Disease↗

Reaction of aspirin with cysteinyl residues of lens gamma-crystallins: a mechanism for the proposed anti-cataract effect of aspirin.

Incubation of lens crystallins with aspirin inhibits the development of opacities caused by cyanate. Cyanate-induced opacities are thought to be due to carbamylation of the lysyl residues which causes a decrease in the protein charge and subsequent conformational changes that permit disulfide bonding. Because aspirin can also react with lysyl residues, it has been proposed that the aspirin inhibition of cataractogenesis is due to acetylation of the lysyl residues which would block their reaction with cyanate. However, acetylation of lysyl residues also lowers the protein charge and would be expected to effect changes in protein conformation similar to those caused by carbamylation. Therefore, acetylation of the lysyl residues is not a satisfactory explanation for the inhibitory effect of aspirin on lens opacification. Our investigations of the reactions of cyanate and aspirin with bovine gamma II-crystallins show that the cysteinyl residues are also carbamylated and acetylated at pH 7.4. At this pH, the carbamylation at the cysteinyl residues is reversible, leading to regeneration of the thiol group and disulfide bonding. In contrast, the acetylation at cysteinyl residues is stable at pH 7.4 and can prevent disulfide bonding. This difference in stability explains how cyanate promotes, and aspirin inhibits, cataractogenesis.

Acetylation↗

Determination of amide hydrogen exchange by mass spectrometry: a new tool for protein structure elucidation.

A new method based on protein fragmentation and directly coupled microbore high-performance liquid chromatography-fast atom bombardment mass spectrometry (HPLC-FABMS) is described for determining the rates at which peptide amide hydrogens in proteins undergo isotopic exchange. Horse heart cytochrome c was incubated in D2O as a function of time and temperature to effect isotopic exchange, transferred into slow exchange conditions (pH 2-3, 0 degrees C), and fragmented with pepsin. The number of peptide amide deuterons present in the proteolytic peptides was deduced from their molecular weights, which were determined following analysis of the digest by HPLC-FABMS. The present results demonstrate that the exchange rates of amide hydrogens in cytochrome c range from very rapid (k > 140 h-1) to very slow (k < 0.002 h-1). The deuterium content of specific segments of the protein was determined as a function of incubation temperature and used to indicate participation of these segments in conformational changes associated with heating of cytochrome c. For the present HPLC-FABMS system, approximately 5 nmol of protein were used for each determination. Results of this investigation indicate that the combination of protein fragmentation and HPLC-FABMS is relatively free of constraints associated with other analytical methods used for this purpose and may be a general method for determining hydrogen exchange rates in specific segments of proteins.

Amides↗

5-HT3 receptors which modulate [3H]5-HT release in the guinea pig hypothalamus are not autoreceptors.

The 5-HT3 agonist 2-methyl-5-HT had previously been shown to enhance the electrically evoked release of [3H]5-HT from preloaded slices of the guinea pig brain. In the present study, 2-methyl-5-HT (1 microM) was also found to increase the K+ evoked release of [3H]5-HT from preloaded slices of the guinea pig hypothalamus and this effect was blocked by the selective 5-HT3 antagonist ondansetron. In the presence of tetrodotoxin, the enhancement of the K(+)-evoked release of [3H]5-HT by 2-methyl-5-HT in hypothalamus slices was blocked, thus suggesting that the 5-HT3 receptors mediating this effect are not located directly on 5-HT terminals. In agreement with this, 2-methyl-5-HT did not alter the K(+)-evoked release of [3H]5-HT in a synaptosomal preparation of the same brain structure, even at a concentration 10-fold greater than that used in the slices. Taken together, these data indicate that these facilitatory 5-HT3 receptors are not located on 5-HT terminals in the guinea pig hypothalamus and therefore are not autoreceptors.

Animals↗

The reaction of bovine lens alpha A-crystallin with aspirin.

Acetylation of the lysines of bovine lens alpha A-crystallin has been examined after 0-48-hr incubations of whole alpha-crystallins in 100 mM aspirin. The alpha A-crystallins were isolated after the incubation, proteolytically digested into peptides which were separated by reversed phase HPLC and analysed by mass spectrometry. For the reaction conditions used in this investigation, acetylated lysyl residues were the principal products. The extent of acetylation was quantified from the intensities of the peaks in the fast atom bombardment mass spectra of the modified and unmodified peptides. The modified lysine containing peptides demonstrated that all seven lysyl residues of alpha A-crystallin reacted with aspirin; the extent of acetylation at each lysyl residue varied. Plots of the extent of acetylation vs. time were used to calculate rate constants for the reaction at each lysyl residue. The rate constant for the acetylation of Lys 166, the most reactive, was about seven times greater than for Lys 88, the least reactive. These rate constants were used to calculate the yield of predicted products for the reaction of alpha-crystallin with therapeutic concentrations of aspirin. Comparison of the yield of acetylated alpha-crystallin with the yield of carbamylated alpha-crystallin that might occur due to renal failure indicates that aspirin is not likely to be an effective inhibitor of cataract due to carbamylation of lysyl residues.

Acetylation↗