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P Wilcox

Publications and source records attributed to P Wilcox.

At least 37 records · Page 2Linked to original sources

Oxygen cost of inspiratory loading: resistive vs. elastic.

We measured the O2 cost of breathing (VO2resp) against external inspiratory elastic (E) and resistive loads (R) when end-expiratory lung volume, tidal volume, breathing frequency, work rate, and pressure-time product were matched in each of six pairs of runs in six subjects. During E, peak inspiratory mouth pressure was 65.7 +/- 1.8% (SD) of the maximum at functional residual capacity. However, during resistive runs, peak inspiratory mouth pressure was 41.1 +/- 2.8% of the maximum at functional residual capacity. In 36 paired runs, where both work rate and pressure-time product were within 10%, VO2resp for E was less than for R (81 and 96 ml/min, respectively; P less than 0.01). During loaded and unloaded breathing with the same tidal volume, we measured the changes in anteroposterior diameter of the lower rib cage in five subjects. In four subjects we also recorded the electromyograms of several fixator and stabilizing muscles. During E and R, the change in anteroposterior diameter of the lower rib cage was -116 +/- 5 and -45 +/- 4% (SE), respectively, of the unloaded value (P less than 0.01), indicating greater deformation during E. Although the peak electromyographic activity was 72 +/- 16% greater during E (P less than 0.01), there was no difference between the loads for area under the electromyogram time curve (P greater than 0.05). However, the time to 50% peak activity was less during R (P less than 0.02). We conclude that, even when work rate and pressure-time product are matched, VO2resp during R is greater than that during E. This difference may be due to preferential recruitment of faster and less efficient muscle fibers.

Adult↗

First degree relatives of breast cancer patients: screening practices and provision of risk information.

Little is known about breast cancer screening knowledge and behaviors among women with a family history of breast cancer. Data gathered from 125 first-degree relatives of breast cancer patients indicated that only 63.3% of women over age 35 "ever" had a mammogram, 53% of women 40 or older reported a mammogram in the last year, and only 36.8% of all participants reported monthly breast self-exam (BSE). Self-reported BSE competence was generally poor. One hundred five (105) (84%) reported a clinical breast exam over the previous year. Only 71 (56.8%) of the women indicated that they had been asked about their family history of breast cancer by their physician, and minimal information about risk related to family history was provided. Worry about developing breast cancer was positively related to mammography use and BSE competence. Confidence in performing BSE and learning BSE from a physician/nurse were both positively related to competence. Women who believed they had control over finding breast cancer in its early stages reported more frequent BSE. Poor compliance of women with a family history of breast cancer in the practice of BSE and utilization of mammography, and lack of risk information provided by physicians mandate a search for effective intervention.

Adult↗

Comparison of Salmonella typhimurium TA102 with Escherichia coli WP2 tester strains.

In 1982, Levin et al. published a paper describing a new Salmonella typhimurium strain, TA102, for detecting mutagenic agents that react preferentially with AT base pairs. This strain has an AT base pair at the critical mutation site within the hisG gene, which is located on a multicopy plasmid, pAQ1; the chromosomal copy of the hisG gene has been deleted. It also has an intact excision repair system, thus facilitating the detection of cross-linking agents, and carries the mutator plasmid, pKM101. Although TA102 has been shown to be reverted by certain mutagenic agents that are not detected in the usual battery of strains (TA1535, TA1537, TA1538, TA98 and TA100), there has been a general reluctance within the field to include TA102 as one of the standard screening strains. This may in part result from the difficulties which have been experienced in many laboratories in maintaining the strain, and in obtaining reproducible spontaneous and induced revertant counts. At Glaxo we routinely include certain Escherichia coli strains in our microbial test battery, and were aware that some of the genetic features offered by TA102 were already being covered by these strains. For example, E.coli WP2 (pKM101) has an AT base pair at the critical mutation site within the trpE gene, is excision proficient (and thus will detect cross-linking agents) and carries the pKM101 plasmid to enhance error-prone repair. From the published literature it was apparent that a number of the 'TA102 specific' mutagens could be detected in E.coli e.g. neocarzinostatin, UV and 8-MOP plus UV.(ABSTRACT TRUNCATED AT 250 WORDS)

Dose-Response Relationship, Drug↗

DNA alkylations and mutation after exposure to ethyl methanesulphonate in mammalian cell lines routinely used in mutagenicity testing.

DNA ethylations were measured in four mammalian cell lines, Chinese hamster ovary CHO, mouse lymphoma L5178Y t k+/-, human lymphoblastoid TK6 and Chinese hamster V79, following exposure to [3H]ethyl methanesulphonate. Concurrent estimates of cytotoxicity and gene mutation were also carried out. Total DNA-binding and relative levels of ethylation at N-7 guanine (N-7G), O6 guanine (O6G) and N-3 adenine (N-3A) were essentially the same in all four cell lines. Differences in response to EMS between the cell lines, namely the greater cytotoxicity in TK6 cells, would therefore appear to reflect subsequent handling of the DNA lesions, rather than different levels of DNA ethylation in the cell lines.

Adenine↗

Determination of benzidine--DNA adduct formation in CHO, HeLa, L5178Y, TK6 and V79 cells.

Using 32P-postlabelling, evidence of DNA adduct formation was sought in six mammalian cell lines, namely Chinese hamster ovary (CHO), human cervical carcinoma (HeLa S3), mouse lymphoma L5178Y tk +/- and L5178Y wild-type, human lymphoblastoid TK6 and Chinese hamster V79, following treatment with benzidine (BZD) in the presence of S-9. Adduct formation was also determined in calf thymus DNA reacted in vitro with N-hydroxy-N'-acetyl-BZD, and in liver DNA from mice given a single intraperitoneal injection of BZD. DNA adducts were detected in the calf thymus DNA sample and in mouse liver DNA, but not in DNA from any of the six cell lines. The absence of adduct formation is consistent with the lack of mutagenicity of BZD in CHO, and V79 and in L5178Y cells at the hprt locus, and in TK6 cells at the tk and hprt loci. These results also suggest that the observed mutagenicity of BZD at the tk locus in L5178Y cells may be due to a mechanism(s) not involving covalent binding to DNA.

Animals↗

Long-term follow-up of symptoms, pulmonary function, respiratory muscle strength, and exercise performance after botulism.

Respiratory muscle weakness occurs commonly at presentation in patients with botulism. Although clinical improvement occurs over several months, symptoms such as fatigue and dyspnea persist in many patients in the long term. To determine whether continued respiratory muscle weakness might contribute to these symptoms, we compared lung function tests, respiratory muscle strength, and exercise performance in 13 patients 2 years after type B botulism. We found that residual symptoms including dyspnea and fatigue were common in botulism patients at 2 years postintoxication. Lung function tests had returned to normal in all patients. Maximal inspiratory and expiratory pressures were similar between botulism patients and control subjects. Evaluation of individual results showed evidence of inspiratory muscle weakness in four of 13 patients with botulism (Plmax less than 65% predicted). Maximal oxygen consumption and maximal workload during exercise were reduced in botulism patients in comparison to control subjects. During exercise, botulism patients had a more rapid and shallow breathing pattern and a higher dyspnea score at a given minute ventilation in comparison to control subjects. Reasons for premature exercise termination in botulism patients were multifactorial. Although respiratory muscle weakness may have been contributory in some patients, most appeared to be limited by reduced cardiovascular fitness, leg fatigue, or reduced motivation.

Adult↗

Concentrated drinking water extracts, which cause bacterial mutation and chromosome damage in CHO cells, do not induce sex-linked recessive lethal mutations in Drosophila.

Concentrated extracts prepared from chlorinated drinking water samples were tested for their ability to induce sex-linked recessive lethal mutations in Drosophila melanogaster. Adult flies were allowed to feed on sucrose solutions prepared using neat or half-strength water extract. The drinking water extracts used for this study were also tested in bacterial fluctuation assays using Salmonella typhimurium TA100 and TA98 and in an in vitro cytogenetic assay using CHO cells. Although the water extracts gave positive results in both of these in vitro tests, there was no evidence of mutagenic activity in the Drosophila studies.

Animals↗

Phrenic nerve function and its relationship to atelectasis after coronary artery bypass surgery.

Atelectasis following coronary artery bypass surgery (CAB) occurs in the majority of patients. To determine the importance of operative variables in the development of postoperative atelectasis and the incidence of phrenic nerve injury caused by topical cold cardioplegic solution, we studied 57 patients (53 male, four female) undergoing CAB. Their mean age, +/- SD, was 58 +/- 13 years. Transcutaneous stimulation was used to evaluate phrenic nerve function preoperatively and postoperatively in 52 patients. An unequivocal paresis of the phrenic nerve was documented in five patients. In an additional 27 patients, the amplitude of the compound diaphragm action potential was reduced postoperatively. However, methodologic limitations did not allow the conclusion that this was secondary to a phrenic axonal degeneration. Discriminant analysis of intraoperative variables showed more severe atelectasis with a larger number of grafts, with a longer operative and bypass time, when the pleural space was entered, when a right atrial drain and a cardiac insulating pad were not used, and with a lower body temperature. It is concluded that phrenic paresis may occur after CAB and topical cold cardioplegia, but that other factors must explain the atelectasis found in the majority of patients.

Cardioplegic Solutions↗

Airway involvement in ulcerative colitis.

Two patients with ulcerative colitis developed progressive obstructive pulmonary disease. In one, the abnormality was a sclerosing peribronchiolitis confined to small airways, while the other demonstrated a large airway fibrotic obliterative bronchitis. A review of airway involvement in ulcerative colitis and a discussion of the possible similarity to another extraintestinal manifestation of ulcerative colitis, sclerosing cholangitis, are presented.

Adult↗

Mutagenic activity of concentrated drinking water samples.

Concentrated drinking water extracts prepared by adsorption onto XAD-2 resin have been tested for their ability to induce chromosome damage in mammalian cells. Extracts prepared from drinking waters derived from upland and lowland sources have been found to induce chromosome aberrations in Chinese hamster ovary (CHO) cells and human lymphocytes in vitro. Although the identity of the compounds responsible for this activity is unknown, they are generated when the water is chlorinated and appear to bind readily to exogenous protein. When groups of mice were dosed orally with a concentrated water extract, however, no evidence of clastogenic activity in bone marrow cells was apparent. The absence of an in vivo effect may indicate that the mutagenic compounds failed to reach the bone marrow. The possibility that genetic damage could be induced in the cells first encountered in the body after ingestion (i.e., cells in the esophagus, stomach, and intestinal tract) is not precluded by this result. The relevance of these findings in evaluating the potential health hazard of mutagenic compounds in drinking water is discussed.

Animals↗

Giant intraarticular loose bodies of the knee. Cases demonstrate spectrum of the lesion.

Synovial chondromatosis is a well-known, well-described clinical and histopathologic entity. Occasionally, loose bodies in the knee joint can continue to grow and become large enough to impinge on joint motion. Extremely large synovial chondromata are relatively rare in the knee joint and have only been described in singular case reports in the orthopaedic literature. We describe two cases representing the spectrum of this disease process occurring in the popliteal fossa, simulating bony and/or soft tissue neoplasm. Case 1 demonstrates a large ossified chondroma, while Case 2 demonstrates a large chondroma without much calcification and with no ossification present. Because of the rarity of these lesions, preoperative staging studies, including CT scan, bone scan, and angiography, are usually warranted to help in the preoperative planning. Open biopsy with adequate tissue sampling is necessary to make an accurate histopathologic diagnosis. Once diagnosis is made, local excision for removal of the mechanical block to motion results in "cure"; local recurrence has not been noted.

Aged↗

Synthesis of 1,6-diaminopyrene from 1,6-dinitropyrene and its S9 dependent mutagenicity to S. typhimurium.

1,6-Dinitropyrene elicits a potent mutagenic response in a range of microorganisms in the absence of auxiliary metabolism (S9 mix). This activity is considered to be dependent upon nitroreductase enzymes endogenous to the marker organism producing electrophilic species from one or both of the nitro groups. In order to evaluate this suggestion 1,6-diaminopyrene has been synthesised, characterized and found to elicit a mutagenic response in strain TA98 of Salmonella typhimurium, but only when evaluated in the presence of S9 mix. The active dose-range of the diamino compound was 10(4) times higher than that of the parent dinitro compound.

Dose-Response Relationship, Drug↗

The clastogenic activity of dinitropyrenes in a rat-liver epithelial cell line.

The ability of 1,6-dinitropyrene and 1,8-dinitropyrene to induce chromosome aberrations has been examined in a rat epithelial cell line (RL4). Both compounds were found to be potent clastogenic agents in these cells, inducing predominantly chromatid type abberations. The number of aberrant metaphases was dose-related up to 1.25 micrograms/ml, after which the response showed a plateau at a frequency of around 60%. The number of chromatid gaps per 100 cells also increased linearly with concentration from 3.5 in the control cultures up to 117 with 1,6-DNP (1.25 micrograms/ml) and 98 with 1,8-DNP (2.5 micrograms/ml), indicating that the induction of chromatid gaps was a valid and sensitive measure of chromosome damage in this cell line. The fact that a positive result as obtained in RL4 cells implies that these cells contain enzyme systems which are capable of converting dinitropyrenes to a mutagenic form.

2,4-Dinitrophenol↗

The genetic activity of dinitropyrenes in yeast: unusual dose response curves for induced mitotic gene conversion.

1,6-Dinitropyrene (1,6DNP) and 1,8-dinitropyrene (1,8DNP) were tested for their ability to induce mitotic gene conversion at the trp 5 and his 4 loci in the yeast Saccharomyces cerevisiae JD1. Both compounds were shown to be potent inducers of gene conversion in yeast, with 1,6DNP being somewhat more active than 1,8DNP. Unusual dose-response curves were obtained in that toxicity and genetic activity decreased at the higher concentrations examined. This reduction in genetic activity may reflect a decrease in the ability of yeast cells to convert the dinitropyrenes to their mutagenic forms when the concentration of the compounds exceeds a certain level.

Cell Survival↗

Role-played and hypnotically induced simulation of psychopathology on the MMPI.

The differential effects of role-played vs. hypnotically induced simulation of a paranoid syndrome on diagnostic and validity scales of the MMPI were tested with 30 female undergraduate Ss. Hypnotized Ss given the paranoid syndrome suggestion simulated the MMPI more accurately than did role-playing Ss. The F scale and Gough F-K index of dissimulation identified the role-playing group, but not the hypnosis with simulation suggestion group. It was concluded that further refinement of the validity scales of the MMPI is needed to improve their effectiveness in detecting deception on this test.

Adolescent↗