Accelerated nodulosis in a patient with psoriasis and arthritis during treatment with methotrexate.
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Aged↗
Biomedical subjects
M D Smith
Publications and source records attributed to M D Smith.
Consideration of potential immunological problems in the application of xenogenic hybrid liver support.
Hybrid liver support systems (LSS) for the use of pig liver cells are under development for extracorporeal therapy of acute liver failure and for bridging to liver transplantation. A literature overview about possible immunological side effects of a clinical application is given. The data summarised from experimental studies and those clinical applications of porcine cells reported so far, suggest that clinical use of LSS utilising porcine cells and an immuno-isolation membrane should not be compromised by severe immunological complications. The reported data suggest that clinical application should be conducted in conjunction with carefully planned immunological monitoring. Only after such applications of LSS have been carried out and further data have been evaluated, might one be able to judge the immunological consequences of broader application of hybrid liver support.
Animals↗
Lysine residues at positions 234 and 236 in yeast porin are involved in its assembly into the mitochondrial outer membrane.
Various point mutations of lysyl residues in yeast mitochondrial porin (283 residues) were tested for their ability to assemble in vitro into the outer membranes of intact yeast mitochondria. Assembly was evaluated by protection from proteinases. The extent of assembly of two of the mutants, K234E and K236E porins, was much less than for wild-type in either post-translational or co-translational assembly assays. Lysine to glutamate mutants at other positions and K234R porin assembled as well as wild-type, but K234Q porin was poorly inserted. When both Lys-234 and Lys-236 were mutated, K234R/K236R porin was inserted better than K234Q/K236Q porin, which was inserted better than K234E/K236E; however, none of these mutants assembled as well as wild-type porin. It was concluded that optimal assembly of yeast porin depended on the presence of positively charged residues at both positions 234 and 236 and a lysine at one of these positions. After undergoing the assembly reaction, mutants that were vulnerable to proteinase K (i.e. K234E, K234Q, and K236E porins) seemed to be incompletely digested and were, to varying degrees, resistant to extraction by Na2CO3 (pH 11.5). These experiments suggested that these mutants were incompletely inserted into the outer membrane. Both Lys-234 and Lys-236 are included in an internal pentapeptide, VKAKV, that is conserved in porins from protists, plants, and animals, and it is possible that, at least, the lysines in this tract are one of the signals for the membrane assembly of these proteins.
Amino Acid Sequence↗
Effects of ex vivo manipulation on the expression of cell adhesion molecules on neutrophils.
In vitro studies of neutrophil adhesion generally utilise purified populations and are often performed at 37 degrees C. This study determines the effects of temperature changes and neutrophil separation procedures on the expression of cell adhesion molecules on neutrophils. We found that neutrophil separation procedures involving erythrocyte sedimentation and hypotonic lysis are associated with a significant increase in the expression of both a structural and functional epitope of the beta 2 integrin CD11b, an increase in the expression of sialyl Lewisx (CD15s) and the hyaluronate receptor (CD44) as well as a significant decrease in L-selectin (CD62L) expression. Separated neutrophils are also more resistant than unseparated neutrophils to PMA induced upregulation of a functional epitope of CD11b. Incubating neutrophils at 37 degrees C is associated with increases in the expression of structural and functional epitopes of CD11b. Neutrophil separation is also associated with increases in the expression of both structural and functional epitopes of CD11b which is greater when neutrophil separation is performed at room temperature compared with neutrophil separation at 0-4 degrees C. However, this difference is lost when the latter are incubated at 37 degrees C. Furthermore, neutrophil separation at both 0-4 degrees C and room temperature is associated with a significant increase in CD15s expression. This increase is less when separation is performed at room temperature. These findings suggest that neutrophil separation should be performed at room temperature unless the cells are going to be used at 0-4 degrees C. Researchers using purified neutrophil populations need to be aware of these significant structural and functional changes when extrapolating in vitro results to in vivo situations.
Antibodies, Monoclonal↗
Administrative databases' complication coding in anterior spinal fusion procedures. What does it mean?
STUDY DESIGN: A review of a cohort of 310 consecutive patients who underwent anterior spinal fusion was performed to evaluate the accuracy of hospital ICD-9-CM complication coding. OBJECTIVES: To better understand the clinical significance of conclusions suggested by studies that rely on electronic administrative databases for their data source. SUMMARY OF BACKGROUND DATA: Despite their availability, there have been no studies to date that have evaluated the accuracy of ICD-9-CM administrative databases as they relate to the actual clinical experience in spinal procedures. METHODS: A physician and a research technician independently reviewed the primary medical records for the occurrence of complications. This data was compared with the hospital-acquired ICD-9-CM coded complications. RESULTS: The physician reviewer identified 152 complications in 119 patients, with 32 different types of complications. The research abstracter identified 175 complications in 130 patients, with 34 different types of complications identified. Hospital ICD-9-CM coding identified 105 complications in 80 patients, including only 11 different ICD-9-CM codes. Overall, 27% of ICD-9-CM complication codes were listed as "unspecified or unclassified complications, reactions, or misadventures," and contained no meaningful clinical information. Cardiac and pulmonary complications were over-estimated and wound infections and genitourinary and gastrointestinal complications were underestimated by ICD-9-CM coding. CONCLUSIONS: Studies of complications of spinal procedures using data derived from hospital ICD-9-CM complication codes may be intrinsically flawed because the data available to researchers from these electronic databases may be inaccurate.
Adolescent↗
Testing for HIV infection at home.
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Adolescent↗
Transesophageal echocardiography in the diagnosis of traumatic rupture of the aorta.
BACKGROUND: Rupture of the aorta is a major cause of death after motor vehicle accidents. Survival depends on early diagnosis, and emergency aortography is the standard imaging method. Although transesophageal echocardiography is noninvasive and can provide high-resolution images of the aorta, information about its value in patients with trauma is limited. We conducted this study to assess prospectively the value of transesophageal echocardiography in the emergency evaluation of patients at risk for aortic injury. METHODS: Transesophageal echocardiography of the aorta was attempted in 101 patients admitted to the emergency room with a diagnosis of possible traumatic rupture of the aorta. Echocardiography and aortography personnel were notified simultaneously of the arrival of the patient, and the two tests were performed sequentially by operators who were blinded to the results of the other test. The sensitivity and specificity of transesophageal echocardiography were calculated on the basis of the results of aortography of the arch, surgery, or autopsy. RESULTS: Transesophageal echocardiography was attempted in 101 patients. The study was successfully performed in 93 patients but could not be completed in 8 because of lack of cooperation on the part of the patient (7 patients) or maxillofacial trauma (1 patient). Despite a high injury-severity score (mean, 29.6), transesophageal echocardiography was performed without complications, and within a mean (+/- SD) of 29 +/- 12 minutes. Eleven of the 93 studies (12 percent) demonstrated rupture of the aorta near the isthmus. The findings were confirmed in 10 of the 11 patients by aortography (9 patients), surgery (9 patients), or autopsy (1 patient), yielding a sensitivity of 100 percent and specificity of 98 percent for the detection of injury to the aorta. There was one false positive echocardiogram. CONCLUSIONS: Transesophageal echocardiography is a highly sensitive and specific method of detecting injury to the thoracic aorta. This technique can be used safely and quickly in critically injured patients with suspected traumatic rupture of the aorta and compares favorably with arch aortography.
Acute Disease↗
Echo Doppler evaluation of patients with acute mitral regurgitation: superiority of transesophageal echocardiography with color flow imaging.
Acute mitral regurgitation is a medical emergency that requires prompt, accurate diagnosis and urgent therapy. Although the use of echo Doppler imaging has been described in these patients, preliminary observations have suggested that color flow Doppler performed from the standard transthoracic windows may underestimate the severity of mitral insufficiency in this setting. The aim of this study was to compare transesophageal color Doppler quantitation of regurgitation with results obtained from standard transthoracic windows in patients with acute, severe mitral regurgitation. Two-dimensional echocardiography with pulsed, continuous, and color flow Doppler was performed by both transthoracic and transesophageal methods in 16 consecutive patients who were documented to have acute severe mitral insufficiency by catheterization. Transthoracic and transesophageal scans were reviewed by two blinded observers and assessed for the detection of mitral regurgitation by transthoracic pulsed wave (81%), continuous wave (100%), and color flow Doppler (81%) compared with transesophageal color flow imaging (100%; p = NS). Severity of mitral regurgitation was graded as none, mild, moderate, or severe on the basis of existing transthoracic pulsed wave and color flow criteria and compared with transesophageal color flow grading. At first examination patients were critically ill, with elevated pulmonary wedge pressures (mean 27 +/- 7 mm Hg) and V waves (mean 45 +/- 10 mm Hg). Fifteen of the patients underwent emergency surgery, and the overall hospital mortality rate was 12%. Maximal color flow jet areas were significantly greater on transesophageal scanning (mean 10.5 cm2) compared with transthoracic color jets (mean 2.3 cm2).(ABSTRACT TRUNCATED AT 250 WORDS)
Acute Disease↗
The majority of Fc gamma RIII-positive gamma delta T cells do not express HLA-DR in patients with primary Sjögren's syndrome.
The percentages of circulating gamma delta T cells and the proportions of these expressing Fc gamma RIII (CD16) or HLA-DR in patients with primary Sjögren's syndrome (pSS) and controls were determined using monoclonal antibodies and flow cytometry. There was no significant difference in the percentages of gamma delta T cells in the pSS patients compared with controls. There was, however, a significant increase in the proportions of both CD16+ and HLA-DR+ gamma delta T cells in pSS patients. A 3-colour immunofluorescence technique demonstrated that these two markers were mutually exclusive and therefore may identify either subpopulations of gamma delta T cells or different stages of the activation process.
Female↗
The influence of medium composition on the maintenance of cytochrome P-450, glutathione content and urea synthesis: a comparison of rat and sheep primary hepatocyte cultures.
Rat and sheep primary hepatocytes have been cultured in four different medium formulations: Williams' E, Chee's, Medium 199 and Modified Earle's. The total cytochrome P450 content, intracellular concentration of reduced glutathione, rate of urea synthesis and total protein content of cultures of cells from both species in each medium have been determined. Modified Earle's and Chee's medium proved to be the most favourable formulations for the culture of rat hepatocytes. After 48 h, cells cultured in Modified Earle's had significantly more cytochrome P450 and a significantly greater rate of urea synthesis than cells in any other medium. After 6 days in culture the difference in cytochrome P450 levels between rat hepatocytes in Chee's medium and those in Modified Earle's medium was abrogated. The difference in the rate of urea synthesis between rat hepatocytes cultured in each of these two media was shown to be more dependent on the medium in which the cells were maintained during the period of urea synthesis measurement than on the medium in which the cells had been previously cultured. Sheep hepatocytes cultured in Chee's medium ruptured and died within 24 h. Apart from this, sheep cells were less sensitive to changes in medium formulation than were rat hepatocytes. The initial plating efficiency was lower in sheep cells. Total cytochrome P450 content was the most discriminatory of the four parameters for evaluating the status of rat hepatocyte cultures. However, urea synthesis may be the most useful parameter for assessment of hepatocyte function in hybrid liver devices such as bioartificial liver support systems where access to the cells during operation of the device is restricted.
Ammonia↗
Treatment of ocular fungal infections with oral fluconazole.
PURPOSE: We treated five patients who had ocular fungal infections with oral fluconazole to determine its safety and effectiveness. METHODS: We reviewed the case histories of the five patients. One patient had coccidioidomycosis and four had endogenous Candida endophthalmitis. RESULTS: The intraocular fungal infection resolved in all patients. CONCLUSION: Fluconazole appears to be a safe and effective antifungal agent that can be administered orally and may be a useful agent for treating some intraocular fungal infections.
Administration, Oral↗
Echocardiography in the evaluation of thoracic trauma.
Echocardiography has become a useful diagnostic modality in the evaluation of cardiovascular injury after thoracic trauma. Valuable information about cardiac wall motion, valvular function, pericardial effusions, and ventricular volume status can be obtained without significant risk. More recent application for the diagnosis of traumatic aortic disruption provides a safer, easier, less expensive, and more accurate method for detecting these injuries. Cardiac evaluation with TTE is unsuccessful in approximately 20% of examinations and is unable to provide the image resolution of the more invasive transesophageal approach.
Aorta, Thoracic↗
Pharmacist counseling and outcomes of smoking cessation.
The Pharmacists Educating Patients Program (PEPP) was designed (1) to provide pharmacists with smoking cessation consultation guidelines for patients on nicotine transdermal therapy and (2) to test the effectiveness of these pharmacists' consultation services. More than 6,500 pharmacies and 40,220 patients participated in this program. One year after treatment began, a survey of 2,001 patients on nicotine transdermal therapy found that those who had not joined a comprehensive smoking cessation program (86.5%) but were counseled by a pharmacist had a self-reported smoking cessation rate of 37% at the end of treatment, and 33% at an average of 10 months after treatment. The average length of treatment was five weeks. Patients who participated in a comprehensive behavioral smoking cessation program, such as SmokEnders, and who also received counseling from their pharmacists (13.5% of surveyed patients) had a quit rate of 62% at the end of treatment and 45% after 10 months. Among surveyed patients, those who stopped smoking reported that their pharmacists' counseling had been more intense and more helpful than the counseling reported by those who did not stop smoking. In addition, those who stopped smoking had more pharmacist counseling interventions and more weeks on nicotine patch treatment than did those who failed to stop smoking. Results of this study show that pharmacists who counsel patients on nicotine transdermal therapy about smoking cessation can improve outcomes.
Administration, Cutaneous↗
The metaphysics of ADHD a unifying case scenario.
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Attention Deficit Disorder with Hyperactivity↗
Elevated serum procalcitonin levels in patients with melioidosis.
The prognostic value of serum procalcitonin levels in 43 patients with acute melioidosis, an infection with a wide range of clinical manifestations, was assessed. In eight patients with mild localized infections, the median procalcitonin levels were 0.13 ng/mL (range, 0.02-0.46 ng/mL), which were similar to those in 19 healthy controls (median, 0.07 ng/mL; range, 0.03-0.15 ng/mL). In the patients with severe infections, the initial procalcitonin levels were significantly higher in the patients who died (median, 350 ng/mL; range, 63-3,538 ng/mL) than in the survivors (median, 19 ng/mL; range, 0.55-387 ng/mL) (P < .0001); 16 of 19 patients with procalcitonin levels of > 100 ng/mL died, compared with 2 of 16 patients with levels of < 100 ng/mL (relative risk, 6.7; 95% confidence interval, 1.8-25; P = .0001). In those patients who survived, the subsequent procalcitonin levels reflected closely the clinical course of their infection. The serum concentration of procalcitonin correlates well with the severity of Pseudomonas pseudomallei infection and is comparable with other acute-phase markers. However, this prognostic indicator and marker of continuing disease activity is not specific to melioidosis and could be applied to other severe infections.
Acute Disease↗
Prognostic significance of quantitative bacteremia in septicemic melioidosis.
Pour-plate blood cultures were performed for 418 adult patients with suspected septicemic melioidosis in order to determine the relationship between quantitative bacterial counts in blood and mortality. Of 108 patients whose hemocultures yielded Burkholderia pseudomallei, 53% had < 10 cfu/mL and 24% had > 100 cfu/mL. High blood bacterial counts were more common than reported previously with regard to other gram-negative septicemias and were significantly associated with the development of hypotension (P = .008) and a fatal outcome (P = .0001). The overall mortality was 63% (95% CI, 53%-72%); however, counts of < or = 1 cfu/mL were associated with a mortality of 42% (95% CI, 28%-58%), compared with 96% (95% CI, 80%-100%) with counts of > 100 cfu/mL. Heavy bacteremia (> 50 cfu/mL) is common in septicemic melioidosis and is usually fatal.
Adolescent↗
Up-regulation of p21WAF1/CIP1 in psoriasis and after the application of irritants and tape stripping.
p21WAF1/CIP1 is a nucleoprotein that was initially characterized by its ability to be regulated transcriptionally by p53 and by its ability to mediate growth arrest by binding to cyclin-dependent kinases. Although p21WAF1/CIP1 is thought to mediate the effects of p53 in causing growth arrest, p21WAF1/CIP1 is also regulated in a p53-independent manner, e.g., during terminal differentiation of some cell lines. Growth factors including epidermal growth factor also induce p21WAF1/CIP1 through p53-independent pathways. Because the epidermal growth factor signaling pathway is abnormal in psoriatic epidermis, we studied p21WAF1/CIP1 expression, using in situ hybridization and immunohistochemistry, in psoriasis. Both p21WAF1/CIP1 mRNA and protein were significantly elevated in untreated psoriatic plaques compared with uninvolved psoriatic skin (p < 0.0001), with the up-regulation of p21WAF1/CIP1 being predominantly suprabasal. This increase was accompanied by a small increase in p53 protein expression of uncertain significance. Furthermore, p21WAF1/CIP1 expression was induced in skin after sellotape stripping and by the application of agents, such as dithranol, that are capable of inducing hyperproliferation. The pattern of p21WAF1/CIP1 expression observed is consistent with a role in induction and maintenance of differentiation. Our experiments, however, cannot determine whether the abnormalities of p21WAF1/CIP1 epidermal expression in psoriasis and after insult are independent of changes in p53 expression.
Anthralin↗
Use of in situ detection of histone mRNA in the assessment of epidermal proliferation: comparison with the Ki67 antigen and BrdU incorporation.
The labelling index is commonly used as a measure of proliferation. However, the use of tritiated thymidine or BrdU labelling of S-phase cells is limited to prospective samples. We have employed an oligonucleotide cocktail complementary to the mRNA species encoding the replication-dependent histones H2B, H3 and H4 for non-isotopic in situ hybridization (NISH), and have compared the resultant proliferation indices in normal skin with those obtained by bromodeoxyuridine (BrdU) incorporation and by Ki67 immunohistochemistry (IHC) using the monoclonal antibody MIB1. In addition, we compared the staining characteristics of histone NISH and Ki67 IHC in a further 25 samples from a variety of inflammatory dermatoses and neoplastic conditions, as well as from normal skin. In normal skin, S-phase (histone NISH and BrdU) and cycling (Ki67) cells were confined to the basal and low suprabasal layers. The labelling indices determined by histone NISH and BrdU incorporation were similar, whereas that of Ki67 IHC was four times greater. In biopsies from hyperproliferative dermatoses and dysplastic or malignant lesions, the number of histone NISH- and Ki67 IHC-positive cells was generally elevated; in accordance with the differential expression of these two markers during the cell cycle, MIB1 consistently gave higher results. The advantage of histone NISH over Ki67 IHC is that it is a marker of the same part of the cell cycle as BrdU incorporation. However, the combined use of both histone NISH and Ki67 IHC to measure two cell cycle parameters, namely S-phase and the number of cycling cells, allows more detailed retrospective study of epidermal proliferation than has been possible previously.
Bowen's Disease↗