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Biomedical subjects

B Ward

Publications and source records attributed to B Ward.

At least 91 records · Page 5Linked to original sources

Mobile telephones interfere with medical electrical equipment.

Electromagnetic interference in medical electrical equipment has not been a serious problem in recent years even with the proliferation of analogue mobile phones and two-way handheld radios. With the introduction of GSM digital mobile phones into Australia we have conducted measurements and found that, within 2m, the electric fields from digital mobile phones can exceed the immunity level of 7 V/m recommended by the US Food and Drug Administration (FDA) for medical electrical equipment. Current analogue mobile phones were shown to produce electric fields that exceed the 7 V/m level only at relatively shorter distances. In another test, both analogue and digital mobile phones were operated close to a range of typical medical electrical equipment. It was found that existing equipment generally meets the FDA standard, but digital mobile phones caused a variety of artefacts and alarm conditions. This problem must be addressed by the medical engineering profession; in the meantime, nursing and other staff should be educated to recognise these problems and restrictions must be placed upon the use of mobile phones in hospitals.

Electromagnetic Fields↗

Immunologic parameters 2 years after high-titer measles immunization in Peruvian children.

Immunization with high-titer measles vaccines has been associated with excess mortality in children 2-4 years after vaccination. In this study, immunologic parameters in 64 Peruvian children who had been immunized an average of 27 months earlier with high-titer vaccines were compared with parameters in 76 recipients of low-titer vaccines. Delayed-type hypersensitivity, lymphocyte phenotype distributions by flow cytometry, and lymphoproliferation after phytohemagglutinin (PHA) stimulation were assessed. High-titer recipients had smaller indurations to tetanus, diphtheria, and Proteus (P < .05) antigens, decreased PHA stimulation (P = .04), and a lower percentage of CD4+ lymphocytes (P = .04) than low-titer recipients. After adjustment for sex, concurrent illnesses, and other variables in regression analyses, high-titer recipients had a lower percentage of CD4+ lymphocytes (P = .025) and decreased lymphocyte proliferation to PHA (P = .058). These results may provide a clue to the pathogenesis of delayed excess mortality after high-titer measles vaccination in some developing countries.

Cell Division↗

Transmission of human papillomaviruses from mother to child.

Exfoliated cervical epithelial cells from women 6 weeks postpartum were analyzed for human papillomavirus (HPV) DNA using the polymerase chain reaction, and results were compared with those from buccal mucosal smears from their babies. Eleven mothers had genital genotypes of HPV in their cervical smears, and the children of 8 of these had HPV of the same genotype in buccal mucosal cell samples. Nineteen mothers had no HPV DNA detected in their cervical smears, and 1 of the buccal mucosal cell samples from their children was positive for HPV DNA (p < 0.0001). Contamination of a child's mouth with 'genital' HPV from a mother's cervix appears to occur commonly at birth or in the perinatal period, and to persist for at least 6 weeks. This observation has implications for the epidemiology and management of HPV associated cancer and precancerous conditions in the cervix and the mouth.

Cervix Uteri↗

The development of alcohol strategies in England and Wales.

Alcohol has become a major public health problem in the UK. In order to coordinate the work of both statutory and non-statutory agencies more efficiently and effectively, a government circular HN(89)4 has emphasized the need for development of local multi-agency alcohol misuse prevention strategies. Despite expressed enthusiasm for alcohol strategies, information about their development, effectiveness and overall national progress is scarce and needs to be improved. This national survey reports the most recent and accurate information about the development of district and regional alcohol strategies in England and Wales. Although only 51 (27%) districts stated they had a strategy, it was encouraging to find 90 (47%) other districts that were in the process of, or planning to develop such a document. Of the 51 districts with a strategy, the following key findings were noted: (1) Forty-three (84%) districts stated that they had started to implement their strategy, but none claimed to have fully implemented it. (2) Thirty-six (71%) districts stated that their strategy had an action plan. (3) Thirty-four (67%) districts stated that their strategy had been officially endorsed by the district health authority. (4) Thirty-eight (76%) districts stated that they had identified an individual or group to monitor the strategies' implementation. The results of the survey could be of interest to the Department of Health, the Faculty of Public Health Medicine, the Health Education Authority and the regional alcohol coordinators.(ABSTRACT TRUNCATED AT 250 WORDS)

Alcoholism↗

Site-specific binding constants for actinomycin D on DNA determined from footprinting studies.

We report site-specific binding constants for the intercalating anticancer drug actinomycin D (Act-D), binding to a 139-base-pair restriction fragment from pBR 322 DNA. The binding constants are derived from analysis of footprinting experiments, in which the radiolabeled 139-mer is cleaved using DNase I, the cleavage products undergo gel electrophoresis, and, from the gel autoradiogram, spot intensities, proportional to amounts of cleaved fragments, are measured. A bound drug prevents DNase I from cleaving at approximately 7 bonds, leading to decreased amounts of corresponding fragments. With the radiolabel on the 3' end of the noncoding strand (A-label), we measured relative amounts of 54 cleavage products at 25 Act-D concentrations. For cleavage of the 139-mer with the label on the 3' end of the coding strand (G-label), relative amounts of 43 cleavage products at 11 Act-D concentrations were measured. These measurements give information about approximately 120 base pairs of the restriction fragment (approximately 12 turns of the DNA helix); in this region, 14 strong and weak Act-D binding sites were identified. The model used to interpret the footprinting plots is derived in detail. Binding constants for 14 sites on the fragment are obtained simultaneously. It is important to take into account the effect of drug binding at its various sites on the local concentration of probe elsewhere. It is also necessary to include in the model weak as well as strong Act-D sites on the carrier DNA which is present, since the carrier DNA controls the free-drug concentration. As expected, the strongest sites are those with the sequence (all sequences are 5'----3') GC, with TGCT having the highest binding constant, 6.4 x 10(6) M-1. Sites having the sequence GC preceded by G are weak binding sites, having binding constants approximately 1 order of magnitude lower than those of the strong sites. Also, the non-GC-containing sequences CCG and CCC bind Act-D with a binding constant comparable to those of the weak GGC sites. The analysis may reveal drug-induced structural changes on the DNA, which are discussed in terms of the mechanism of Act-D binding.

Base Sequence↗

Mid-frequency loss of foveal flicker sensitivity in early stages of age-related maculopathy.

Temporal contrast sensitivity in eyes at risk for exudative age-related maculopathy (ARM) was compared to that in age-matched healthy older eyes. The test stimulus was a foveally viewed, flickering, long-wavelength 2.8 degrees diameter circle in an equiluminant (photopic) surround. Retinal illuminance and decision criterion differences were experimentally controlled. Eyes in the healthy and ARM-risk groups had 20/30 or better Snellen acuity and intraocular pressure of less than 22 mmHg. Nevertheless, the ARM-risk patients were less sensitive to flicker contrast, especially for mid-temporal frequencies. This suggests that flicker sensitivity may be useful in identifying patients at risk for exudative ARM. In addition, comparison with other research reveals a paradox: Mid-temporal frequency sensitivity losses may be attributable primarily to a "high temporal frequency" mechanism.

Aged↗

Foveal flicker sensitivity discriminates ARM-risk from healthy eyes.

The "good" eyes of 13 patients with monocular exudative ARM were compared with age-matched healthy eyes of 19 subjects. Membership in the two study groups was based upon careful clinical evaluation of the tested eye as well as upon status of the fellow eye. We asked whether temporal contrast sensitivity for a long-wavelength, low spatial frequency stimulus can be used to identify the group in which a given eye belongs. Using step-wise discriminant analysis, we found that the ARM-risk and healthy eyes could be classified with 78% accuracy on the basis of foveal flicker sensitivity at two temporal frequencies--14 and 10 Hz (in order of estimated weight.)

Adult↗

Preliminary evaluation of flicker sensitivity as a predictive test for exudative age-related maculopathy.

Flicker contrast sensitivity was tested in the "good" eyes of 13 patients with monocular exudative age-related maculopathy (ARM). The stimulus was a foveal, long-wavelength, low spatial frequency 2.8 degrees circle in an equiluminant (photopic) surround. Two of these ARM-risk eyes have since developed exudative ARM. Compared to healthy age-matched eyes, the two eyes that developed exudative ARM had significantly lower sensitivity at 10-40 Hz up to 9 mo before exudative symptoms appeared. The implications of these results regarding the time-course of ARM and the predictive value of foveal contrast sensitivity testing are considered. Based upon data and theoretical considerations, the authors speculate that sensitivity loss between 10 and 40 Hz is a good predictor of which eyes will develop exudative ARM. This proposal will be tested by new data from current as well as new ARM-risk subjects.

Aged↗

Cancer of the cervix--old and young, now and then.

A study of two 5-year periods, 1960-1964 and 1982-1986, in Queensland is made. Changing patterns of preinvasive and invasive cervical carcinoma in the world literature are discussed. The age of presentation, stage, histology, and results in Queensland for cervical carcinoma are analyzed. There are over 500 patients in each quinquennium. While the total female population has increased 86%, the maximum increase is in patients under 35 years and over 65. There has been a 50% decrease in the incidence of cervical carcinoma, but a doubling under the age of 30. The stage at diagnosis has markedly improved with 88% stage Ib in the young as opposed to 50% formerly. Late-stage disease remains a problem of the aged. The mortality in both time spans increases with age. Histologic patterns show an increase in nonsquamous patterns and increased mortality in the rare patterns. We have no evidence of the emergence of a rapidly progressive carcinoma in the young. Papanicolaou smear and education programs appear to be preventing cervical carcinoma and allowing diagnosis of the disease at an earlier stage and age. This is reflected in a decrease in mortality from 9.6 per 100,000 (1960-1964) to 4 per 100,000 (1982-1986).

Adult↗

Excellent shoulder function is attainable after partial or total scapulectomy. Analysis at prolonged follow-up.

We reviewed six cases of primary sarcomas requiring scapulectomy within the past 13 years in the Surgery Branch of the National Cancer Institute, Bethesda, Md. Five of these patients returned for evaluation of disease status, evaluation of functional defects as determined by muscle group testing, and assessment of daily living skills and limitations. We demonstrated excellent shoulder function with partial scapulectomy and significant impairment with the additional loss of the glenoid fossa. In addition, we developed a thorough method of postoperative evaluation. Involvement of rehabilitation therapists before and after operatively is integral to this process in preparation for surgery and subsequent treatment.

Adult↗

Prognostic significance of tumor ploidy in patients with advanced ovarian carcinoma.

Fresh tumor specimens obtained from 53 consecutive patients with FIGO Stage III ovarian carcinoma were analyzed by flow cytometry. All patients were treated by a standard protocol: maximal tumor excision and cisplatin/cyclophosphamide/adriamycin chemotherapy, and followed-up for at least 24 months. Thirty-two percent of tumors were diploid (DNA index = 1.00) and 68% aneuploid (DNA index greater than 1.00), with more aneuploid tumors being associated with larger residual tumor and poor cellular differentiation. Patients with diploid tumors were found to survive significantly better than those with aneuploid tumors, in terms of survival rate (65% versus 31%), median survival time (33 months versus 13 months), and mean disease-free interval (17.8 months versus 8.2 months). The influence of the amount of residual tumor after primary surgery on survival was only significant in patients with diploid tumors. Our results support previous findings that tumor ploidy is an important prognostic indicator in ovarian cancer. We found aneuploidy to be associated with a poorer clinical outcome in Stage III disease, regardless of the amount of residual tumor after primary surgery and the degree of cellular differentiation.

Adenocarcinoma↗

The effect of condom use on cervical intraepithelial neoplasia grade I (CIN I).

A prospective, controlled study of condom use in patients with histologically-proven CIN I was undertaken. Forty-six patients were studied, 22 by random allocation and 24 by nonrandom allocation to either condom use or non-condom use for 6 months. At the end of this time, patients were reassessed cytologically, colposcopically and histologically. There was no significant difference between the groups with respect to outcome. Six patients' lesions (13%) progressed in this period, 5 (11%) to CIN III. Condom usage is not an effective treatment for CIN I.

Adult↗

Quantitative footprinting analysis using a DNA-cleaving metalloporphyrin complex.

The results of quantitative footprinting studies involving the antiviral agent netropsin and a DNA-cleaving cationic metalloporphyrin complex are presented. An analysis of the footprinting autoradiographic spot intensities using a model previously applied to footprinting studies involving the enzyme DNase I [Ward, B., Rehfuss, R., Goodisman, J., & Dabrowiak, J. C. (1988) Biochemistry 27, 1198-1205] led to very low values for netropsin binding constants on a restriction fragment from pBR-322 DNA. In this work, we show that, because the porphyrin binds with high specificity to DNA, it does not report site loading information in the same manner as does DNase I. We elucidate a model involving binding equilibria for individual sites and include competitive binding of drug and porphyrin for the same site. The free porphyrin and free drug concentrations are determined by binding equilibria with the carrier (calf thymus DNA) which is present in excess and acts as a buffer for both. Given free porphyrin and free netropsin concentrations for each total drug concentration in a series of footprinting experiments, one can calculate autoradiographic spot intensities in terms of the binding constants of netropsin to the various sites on the 139 base pair restriction fragment. The best values of these binding constants are determined by minimizing the sum of the squared differences between calculated and experimental footprinting autoradiographic spot intensities. Although the determined netropsin binding constants are insensitive to the value assumed for the porphyrin binding constant toward its highest affinity sites, the best mean-square deviation between observed and calculated values, D, depends on the choice of (average) drug binding constant to carrier DNA, Kd.(ABSTRACT TRUNCATED AT 250 WORDS)

Base Sequence↗

Esperamicins, a class of potent antitumor antibiotics: mechanism of action.

The esperamicins represent a class of antitumor antibiotics characterized by an unusual chemical core structure and extremely potent cytotoxicity. The mechanism by which these drugs produce cytotoxicity was investigated and found to be related to the formation of single- and double-strand DNA breaks. Using five structurally related analogs, we defined a structure-activity relationship for cytotoxicity in various eukaryotic and DNA-repair-deficient prokaryotic cell lines, for DNA breakage in a human colon carcinoma cell line, and for DNA breakage in vitro in pBR322 DNA. Mild reducing agents such as dithiothreitol greatly increased the DNA breakage potency of these analogs in vitro. Results suggest that the pendant aromatic chromophore of esperamicin A1 may contribute to the uptake of the drug into cells but may also hinder double-strand DNA break formation. Little DNA breakage specificity was observed for the drug in a 139-base-pair fragment of pBR322 DNA. Evidence supports a previously proposed mechanism whereby esperamicins may produce the observed DNA breaks through reduction of the methyl trisulfide group to a thiolate anion followed by a Michael addition of the anion across the alpha,beta-unsaturated ketone. This addition may result in the saturation of the bridgehead double bond, thus allowing the two triple bonds to approach each other, causing cyclization of the diyn-ene to form a phenylene diradical. It is likely that this diradical is the active form of the drug responsible for single- and double-strand DNA breakage produced by this class of antitumor agents.

Aminoglycosides↗

Rate enhancements in the DNase I footprinting experiment.

Footprinting experiments for DNase I digests of a 139-base-pair segment of pBR-322 DNA in the presence of either netropsin or actinomycin D were carried out. Plots of oligonucleotide concentration as a function of drug concentration were analyzed to study the enhancement in cleavage rates at approximately 30 sites, accompanying drug binding at other sites. The pattern of enhancements is not consistent with drug-induced DNA structural changes, but agrees with a redistribution mechanism involving DNase I. Since the total number of enzyme molecules per fragment remains unchanged, drug binding at some sites increases the enzyme concentration at other sites, giving rise to increased cleavage. The consequences of the redistribution mechanism for analysis of footprinting experiments are indicated.

Base Composition↗