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Biomedical subjects

M D Smith

Publications and source records attributed to M D Smith.

At least 307 records · Page 17Linked to original sources

Dissociation of erythema and p53 protein expression in human skin following UVB irradiation, and induction of p53 protein and mRNA following application of skin irritants.

The mechanisms mediating the varied effects of ultraviolet radiation (UVR) on human skin are unclear, although a relationship between erythema and DNA damage is suggested by photosensitivity in xeroderma pigmentosum. Increased p53 expression in response to UVR is thought to reflect direct DNA damage, but recent evidence indicates that UVR also activates membrane and cytosolic signal transduction pathways. In this study, we have investigated the relationship between erythema and p53 induction following UVB and whether this p53 response is specific to UVR. p53 protein expression was determined by immunocytochemistry using the monoclonal antibody DO7, and p53 mRNA expression was examined by non-isotopic in situ hybridization. Incremental doses of UVB were administered to the lower back of eight subjects. Immunostaining revealed that p53 positive nuclei were significantly increased 8 h after suberythemogenic doses of UVB (79 +/- 12), compared to normal unirradiated skin (8 +/- 6, p < 0.0005), but no change in p53 mRNA was seen. Higher UVB doses, which resulted in moderate erythema, resulted in a similar or greater induction of p53 protein. Indomethacin (1% w/v), applied immediately after UVB irradiation, significantly inhibited UVB erythema at 8 h in six subjects (p < 0.005), but did not reduce p53 immunostaining. Dithranol (1 microgram/microliter, n = 8), sodium dodecylsulphate (5%, n = 4), and retinoic acid (0.5%, n = 4), applied for 48 h, caused erythema, significantly increased p53 protein levels (p < 0.05), and also increased p53 mRNA. Our results show that in human skin, UVB-induced p53 elevation can be dissociated from erythema and skin irritants can also induce p53 protein. The induction of p53 mRNA by irritants but not UVR suggests different mechanisms of action.

Adult↗

Hepatocyte culture between woven capillary networks: a microscopy study.

A multi-compartment capillary membrane culture model with independently perfused three-dimensionally woven capillaries was developed for immobilization of hepatocytes in bioreactors. This enables spatial restructuring of cells and enhanced mass transfer performance with more efficient oxygenation and metabolite exchange. Seeding density defines cell behaviour in this model. With low densities cells attach to the membranes and flatten. Increasing density leads to spontaneous formation of aggregates which are immobilized between the capillaries.

Animals↗

Comparison of ofloxacin and ceftriaxone for short-course treatment of enteric fever.

An open, randomized comparison of ofloxacin (200 mg, every 12 h) given orally for 5 days and ceftriaxone (3 g, once daily) given intravenously for 3 days in the treatment of uncomplicated enteric fever was conducted in Ho Chi Minh City, Vietnam. Salmonella paratyphi type A was isolated from six patients. Salmonella typhi was isolated from 41 patients; 63% of these isolates were resistant to multiple antibiotics: ampicillin, chloramphenicol, sulfamethoxazole, trimethoprim, and tetracycline. Of the culture-confirmed cases, treatment with ofloxacin resulted in complete cure of all 22 patients, whereas 18 of 25 patients treated with ceftriaxone were completely cured (P < 0.01). In the ceftriaxone group, there were six acute treatment failures and one relapse. Mean +/- standard deviation fever clearance times were 81 +/- 25 h for ofloxacin and 196 +/- 87 h for ceftriaxone (P < 0.0001). Short-course treatment with oral ofloxacin (5 days) is significantly better than that with ceftriaxone (3 days) and will be of particular benefit in areas where multiresistant strains of S. typhi are encountered.

Adolescent↗

Detection of Streptococcus pneumoniae in sputum samples by PCR.

A method for the detection of Streptococcus pneumoniae in sputum samples by PCR has been developed. The assay employs oligonucleotide primers specific for a portion of the autolysin gene lytA of S. pneumoniae. Other closely related streptococci, Haemophilus influenzae, and Moraxella catarrhalis do not give a positive result in the assay. The assay was capable of detecting between 10 and 100 CFU of S. pneumoniae in distilled water and 1.4 x 10(4) CFU/ml in simulated sputum samples. Sputum samples from 33 patients with acute pneumonia were collected and subjected to culture, PCR, and C-polysaccharide antigen detection by enzyme-linked immunosorbent assay (ELISA). A significant isolate of S. pneumoniae was isolated from 14 patients, of which 13 were positive by PCR and C-polysaccharide antigen ELISA. No positive results were obtained for the 19 patients in whom other pathogens or upper respiratory tract floras only were isolated. The sensitivity of the autolysin PCR is 92.8%, the specificity is 100%, the predictive value of a positive result is 100%, and the predictive value of a negative result is 95%. This suggests that autolysin PCR is suitable for the detection of S. pneumoniae in clinical samples.

Adult↗

Immunofluorescence microscopy for the rapid diagnosis of melioidosis.

A direct immunofluorescent antibody test (DIF) was developed for the rapid diagnosis of melioidosis, a potentially fatal infection caused by Pseudomonas pseudomallei. In a clinical evaluation of 369 sputum, pus, or urine specimens from 272 patients with suspected melioidosis, the DIF had a sensitivity of 73% and a specificity of 99% compared with culture. Using this DIF, a confident diagnosis of melioidosis can now be made within two hours of admission to hospital, compared with the delay of two to four days required for culture results. Consequent early institution of specific antimicrobial therapy may help to save lives.

Fluorescent Antibody Technique↗

Diagnosis of Streptococcus pneumoniae pneumonia by quantitative enzyme linked immunosorbent assay of C-polysaccharide antigen.

AIMS: To evaluate the use of a quantitative enzyme linked immunosorbent assay (ELISA) detecting C-polysaccharide (PnC) antigen in sputum for the diagnosis of Streptococcus pneumoniae infection. METHODS: Specimens of sputum from 60 patients with acute community and hospital acquired pneumonia and infective exacerbations of obstructive airways disease were examined by semiquantitative culture and antigen ELISA. RESULTS: Using a cutoff value of 1 microgram/ml PnC antigen for a positive result, the sensitivity of this assay was 90.3%, specificity 93.1%, predictive value of a positive result was 93.5%, and the predictive value of a negative result 89.6%. CONCLUSIONS: Quantitation of C-polysaccharide antigen in sputum by ELISA distinguishes between carriage of oral bacteria which express PnC-like antigen and infection with S pneumoniae and compares favourably with other diagnostic methods.

Acute Disease↗

Managed care and the poor.

While the momentum for health care reform stems from the concerns of the middle class rather than the poor, we should recognize that managed care--at least as an ideal--can still represent an improvement over the fee-for-service system. For the reality of managed care to approach its promise for underserved communities, issues surrounding cost-sharing, preventive health, traditional providers for the poor, and premium adjustment must be resolved.

California↗

Condom availability in schools: the need for improved program evaluations.

OBJECTIVES: This article examines the impact of contentious local debates on the design and implementation of school-based condom availability programs. METHODS: Information about condom availability in schools was reviewed by 50 leading educators and health officials at a 1992 forum held in Menlo Park, Calif. RESULTS: Few existing condom availability programs were designed to yield definitive data on sexual risk-taking behavior or other measures of program effectiveness. CONCLUSIONS: In the debate over school-based condom availability programs, as in many aspects of human immunodeficiency virus (HIV) prevention programs, scientific, moral, and political concerns overlap. Behavioral research into the potential effectiveness of such programs can help inform debates about fundamental values concerning sexual decision making and privacy, family integrity and parental autonomy, and public health.

Adolescent↗

Deep venous thrombosis and pulmonary embolism after major reconstructive operations on the spine. A prospective analysis of three hundred and seventeen patients.

We performed a prospective study of 317 patients in order to determine the prevalence of deep venous thrombosis after reconstructive operations on the spine; 126 of the patients were examined with duplex ultrasound assessments of the lower extremities to ensure that no asymptomatic thrombi were being missed. Thigh-high stockings and sequential pneumatic compression of the lower extremities were used, in all patients, for prophylaxis against venous thrombosis. No antiplatelet agents or anticoagulant medications were administered. There was no evidence of thrombosis on any of the duplex ultrasound studies. Subsequently, venous thrombosis developed and was treated successfully in one of the 126 tested patients and in one of the 191 untested patients, and a fatal pulmonary embolus developed in one of the untested patients. The over-all clinical prevalence of thrombotic complications was 0.9 per cent (three complications in 317 patients). All three of the patients who had clinical evidence of thrombosis had had an anterior lumbar procedure because of a degenerative disorder or trauma; however, we could not prove that this approach or these diagnoses were significant risk factors for thrombosis (p < 0.05). While it is possible that some thrombi may have escaped both clinical and ultrasonic detection, such thrombi apparently were not enough of a danger to warrant the use of intensive prophylactic procedures that are associated with more risk. On the basis of this prospective study, therefore, we think that routine screening for the detection of asymptomatic thrombosis in patients who have had a procedure on the spine is unwarranted.

Adolescent↗

Physical education teachers' behaviors as related to pupils' psychosocial development in curricular and extracurricular settings.

The purpose of this study was to examine whether teachers' behaviors related to pupils' psychosocial development would differ when physical education teachers taught curricular physical education lessons and when they coached extracurricular school teams. Subjects were 22 physical education teachers who taught and coached basketball in northeastern Colorado and southeastern Wyoming. One physical education lesson on basketball and one basketball practice were videotaped for each subject. These tapes were then coded for frequency of teachers' reactive and spontaneous behaviors with the Coaching Behavior Assessment System. A one-way analysis of variance test indicated that there was no statistically significant difference between the rates teachers used all behaviors during lessons and practices. Hotelling-Lawley trace tests and subsequent repeated-measures multivariate analysis of variance indicated that teachers provided significantly higher rates of punitive mistake-contingent technical instruction, general technical instruction, and general encouragement during extracurricular practices and used a significantly higher rate of behaviors aimed at keeping control during curricular lessons. Unlike previous research on skill-related behaviors, the results did not indicate that teachers' performance suffered dramatically during curricular lessons when compared with performance in extracurricular practices.

Adolescent↗

Detection of Pseudomonas pseudomallei antigen in urine for the diagnosis of melioidosis.

An enzyme-linked immunosorbent assay using a fluorescein isothiocyanate (FITC)-anti-FITC amplification system, has been developed to detect Pseudomonas pseudomallei antigen in urine. The assay was evaluated in 135 patients with acute melioidosis, 194 hospitalized patients with other disorders, and 40 healthy controls. Antigen was detected in the urine of 123 (91%) patients with melioidosis. Urinary antigen was found in 85 (96%) of 89 patients with septicemic melioidosis, all six patients with P. pseudomallei urinary tract infection, and 32 (80%) of 40 patients with other localized infections. Antigen was not detected in the urine of 40 healthy individuals, but the urine of 16 (8%) of 194 hospitalized patients with diagnoses other than melioidosis gave a positive result. Of the false-positive results, 13 of 16 were associated with bacteriuria > or = 10(4) colony-forming units/ml. At a cutoff titer of 1:10, the sensitivity and specificity of the test were 81% and 96%, respectively. Enzyme immunoassay detection of urinary antigen is a valuable and rapid laboratory test for the early diagnosis of acute melioidosis.

Acute Disease↗

Intravascular platelet aggregation and spontaneous contrast.

The purpose of this study was to determine why spontaneous contrast developed after general anesthesia in dogs. Twenty-seven dogs underwent echocardiography before and after pentobarbital or chloralose-urethane general anesthesia. The results showed that none of the 12 dogs receiving pentobarbital and 10 of 15 dogs receiving chloralose-urethane anesthesia developed contrast, in association with large platelet and platelet-neutrophil aggregates (P < 0.01); this effect could also be reproduced in vitro. The administration of adenosine diphosphate or antiplatelet antibody to nine dogs confirmed that intravascular platelet aggregation can cause ultrasonic contrast. The implications of these findings for patients with spontaneous contrast are discussed.

Anesthesia, General↗

Selective expression of V beta families by T cells in the blood and salivary gland infiltrate of patients with primary Sjögren's syndrome.

OBJECTIVE: The T cell infiltration of the salivary gland of patients with Sjögren's syndrome (SS) has been implicated in the pathogenic process of the disease. We examined the representation of V beta subsets in the blood and salivary tissue of patients with SS. METHODS: Circulating T cells from 12 patients and paired samples of blood and labial salivary glands obtained from 8 patients were studied. A panel of monoclonal antibodies directed against the variable region of the T cell receptor was used to enumerate the cells expressing V beta families in the peripheral blood by flow cytometry, and in tissue sections by immunofluorescence. RESULTS: We found an increase of cells bearing V beta 2 family gene products in the circulation, and an increase in both V beta 2 and V beta 8 in the salivary gland infiltrate of patients with SS. No significant difference was noted between the 5 DR3+ patients and 7 DR3- patients studied with regard to the V beta families seen. CONCLUSION: Our data are consistent with a role for specific T cell families in the pathogenesis of SS.

Adult↗

The longterm effect of pulsed corticosteroids on the efficacy and toxicity of chrysotherapy in rheumatoid arthritis.

OBJECTIVE: To follow those patients who participated in a randomized, double blind placebo controlled trial investigating the effect of pulse methylprednisolone treatment in 60 patients with rheumatoid arthritis (RA) starting chrysotherapy. METHODS: Following completion of the original 24-week trial, 47 of the original 60 patients were reexamined between 32 and 67 weeks after completion of the original study. Patients were assessed by a composite clinical score, the Health Assessment Questionnaire (HAQ), erythrocyte sedimentation rate, C-reactive protein and rheumatoid factor levels. RESULTS: At the end of the 24-week trial, the number of patients who responded well to therapy was significantly greater (p < 0.05) in the patients who had received methylprednisolone (17/30) compared with the placebo group (8/30). At the longterm followup assessment, the mean disability score (HAQ) was significantly less (p < 0.05) in patients receiving the initial steroid pulses. No significant difference in drug toxicity or the length of time that patients remained on gold, was observed between the 2 treatment groups. CONCLUSION: Our study supports a beneficial adjunctive role of pulse corticosteroids in patients with RA starting gold therapy.

Adult↗

Health insurance and preventive care sources of children at public immunization clinics.

BACKGROUND: Recent proposals to reform immunization financing aim to help more children receive vaccines at their sources of primary care. Under the current system, referrals of children from the private sector may strain public immunization clinics, but scant information exists on what proportions of public clinic patients actually have insurance or primary care sources. OBJECTIVE: To describe the health insurance, usual sources of health care, and referral patterns of children at low-cost public immunization clinics. DESIGN: Cross-sectional study based on face-to-face, structured interviews. SETTING: Public immunization clinics at three sites in Contra Costa County. PARTICIPANTS: Five hundred thirty-eight parents of children awaiting immunizations. RESULTS: Thirty-four percent of families at these public immunization clinics had Medicaid alone, whereas 24% had private insurance. Of those with private insurance, almost one third had at least partial coverage for vaccines. Sixty-two percent of families had sources of preventive care other than the immunization clinic, and most would have preferred to receive their vaccines at these sources. Most in this group named cost as the main barrier to immunizations at primary care sources; but one third of this group, including almost all the families insured by health maintenance organizations, named the wait for appointments at their usual source of care as the main barrier to receiving vaccines there. Two thirds of Medicaid patients and at least one third of privately insured patients were either uninformed or mistaken about whether their insurance covered vaccines. CONCLUSIONS: Financing reform may improve immunization delivery and reduce the load on public clinics. However, legislation to improve immunization financing will not achieve optimal results unless parent education is improved and organizational barriers are also removed.

California↗

Congenital scoliosis of the cervical or cervicothoracic spine.

Congenital cervical or cervicothoracic scoliosis is an unusual but potentially severe disfiguring cause of spinal deformity in the growing child and adolescent. These forms of scoliosis are among the most infrequently encountered, and therefore, relatively little literature is available to guide the orthopedic surgeon. This article presents a brief overview of the etiology and epidemiology of these rare forms of scoliosis, defines the pathoanatomic variants, reviews the nonoperative treatment methods available, and discusses the role of early recognition and recommendation for spinal arthrodesis of those curves that clearly need surgical stabilization.

Cervical Vertebrae↗

Opacification and border delineation improvement in patients with suboptimal endocardial border definition in routine echocardiography: results of the Phase III Albunex Multicenter Trial.

OBJECTIVES: This study was designed to assess the safety and efficacy of intravenously administered sonicated human serum albumin for enhancing echocardiographic delineation of the left ventricular endocardium and improving assessment of wall motion in patients with incomplete depiction of noncontrast echocardiography. BACKGROUND: Echocardiographic regional wall motion analysis is impaired by incomplete endocardial definition in as many as 10% of patients. Sonicated human serum albumin is a stable contrast material that, unlike other agents, opacifies the left ventricle when administered intravenously. METHODS: One hundred seventy-five patients were enrolled at eight centers on the basis of incomplete echocardiographic endocardial depiction. Sonicated 5% human serum albumin, a stable preparation of air-filled microspheres (size range 1 to 10 microns), was administered intravenously in divided doses: 0.08 ml/kg body weight in all patients, followed by 0.14 and 0.08 ml/kg or a single dose of 0.22 ml/kg, depending on the result of the initial dose. Investigators and independent reviewers blinded to the protocol scored the echocardiograms for degree of left ventricular opacification and improvement of endocardial border depiction. RESULTS: Overall, 81% of patients had at least moderate left ventricular chamber opacification with at least one contrast dose, and endocardial definition was improved in 83%. In the subgroup with inadequate left ventricular opacification from the initial dose, a second, larger dose (0.22 ml/kg) improved endocardial depiction in 64%. No significant side effects occurred. CONCLUSIONS: In patients with incomplete echocardiographic endocardial definition, sonicated human serum albumin is a safe, effective contrast agent that, when administered intravenously, produces left ventricular chamber opacification, improves endocardial depiction and enhances regional wall motion analysis.

Adult↗

Three-dimensional echocardiographic measurement of left ventricular volume in vitro: comparison with two-dimensional echocardiography and cineventriculography.

OBJECTIVES: This study was designed to compare three-dimensional echocardiography, two-dimensional echocardiography and cineventriculography for the purpose of measuring left ventricular volume in vitro. BACKGROUND: Three-dimensional echocardiographic systems have been shown to be highly accurate in measuring the volumes of balloon phantoms. However, three-dimensional techniques have not been compared with standard two-dimensional echocardiography in vitro or with cineventriculography, the clinical standard for left ventricular volume measurement. METHODS: Excised porcine hearts were prepared with an internal latex sheath that could be filled and maintained with a known ("true") volume of liquid. Each heart was then imaged by cineventriculography, standard two-dimensional echocardiography and three-dimensional echocardiography. Left ventricular volumes were calculated from 15 hearts at 25 volumes ranging from 50 to 280 ml by the following methods: 1) biplane cineventriculography using the area-length method; 2) two-dimensional echocardiography by the apical biplane method using a summation of discs algorithm in 15 cases and the single-plane, four-chamber method using a summation of discs algorithm in 10 cases; and 3) three-dimensional echocardiography using a polyhedral surface reconstruction volume computation algorithm based on multiple nonparallel, nonevenly spaced short-axis cross sections. RESULTS: Results were compared with true volume, and a nonparametric analysis of variance was performed. Both measurement bias (systematic error) and imprecision (random error) were assessed. All methods tended to underestimate the true volume (two-dimensional echocardiography -6.1 +/- 17.6%, three-dimensional echocardiography -4.7 +/- 5.0% and biplane cineventriculography -3.9 +/- 8.2%), although differences were not significant. Although there was a significant correlation between the magnitude of measurement bias and the size of the volume being measured for two-dimensional echocardiography and cineventriculography, the bias of three-dimensional echocardiography was fairly constant over the range of volumes. When bias was accounted for, two-dimensional echocardiography was significantly less precise than cineventriculography and three-dimensional echocardiography in terms of percent error (15.3 +/- 11.9%, 5.6 +/- 5.7% and 3.9 +/- 3.4%, respectively). CONCLUSIONS: Three-dimensional echocardiography using a polyhedral surface reconstruction algorithm for volume computation provides accuracy comparable to that of biplane cineventriculography in this in vitro model. Standard two-dimensional echocardiographic volume computation is significantly less accurate than the other two methods.

Algorithms↗