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Biomedical subjects

P Watts

Publications and source records attributed to P Watts.

At least 55 records · Page 3Linked to original sources
PubMed1998

Elderly patients with heart failure: a study of satisfaction with care and quality of life.

OBJECTIVE: To assess the level of patient satisfaction with care, patient quality of life, the relationship between these measures and hospital readmission rates, and patient outcomes. METHODOLOGY: A prospective cohort study was conducted of all patients aged 60 years and over admitted to the John Hunter and Mater Hospitals, in the Hunter Area, in whom congestive heart failure contributed to the need for hospital admission. Patients recruited into the main study were then asked to complete a questionnaire on discharge from hospital. Patients were asked to complete the satisfaction questionnaire on discharge because this would reflect the patients' satisfaction with the overall stay. To provide a baseline quality-of-life score, patients were asked to complete a questionnaire 2 weeks after discharge. FINDINGS: Overall scores on the satisfaction questionnaire were high, indicating that the patients were very satisfied with their care. There were six questions in which 17-35% of patients indicated some degree of dissatisfaction, four related to patient knowledge. No difference in satisfaction was found between patients who had or did not have a readmission. Quality-of-life results showed that patients who had a readmission had a significantly lower quality-of-life score at 12 month follow up (P=0.007) than those without a readmission. CONCLUSION: This finding has supported our hypothesis that a higher level of quality of life would be related to fewer readmissions.

Adult↗
PubMed1998

Acceptance of nurse practitioners and physician assistants in meeting the perceived needs of rural communities.

Nurse practitioners and physician assistants have provided a partial solution to the shortage of primary care services in medically underserved rural areas. This paper describes the results of a study exploring community acceptance of nurse practitioners and physician assistants in rural medically underserved areas. Community acceptance in the context of this study implies not only satisfaction with care received, but also willingness of the community to support NP/PA practice through its infrastructure and encourage members to initially seek and continue to receive care from an NP or PA. Five focus groups were conducted in each of five rural medically underserved communities. The two most pervasive findings were the lack of previous exposure to NPs and PAs and the general belief that NPs and PAs would be accepted in these communities if certain conditions could be met. The theme of conditional acceptance included both personal and system factors. Personal factors included friendliness, competence, willingness to enter into the life of the community, and the ability to keep information confidential. System factors considered critical for acceptance included service type, integration with the existing health care system, cost, geographic proximity, and availability. The results of this study offer insight into community attitudes and suggest marketing strategies for those who plan to introduce NP or PA services into rural communities.

Focus Groups↗
PubMed1998

The TAATGARAT motif in the herpes simplex virus immediate-early gene promoters can confer both positive and negative responses to cellular octamer-binding proteins when it is located within the viral genome.

The TAATGARAT motif in the herpes simplex virus (HSV) immediate-early (IE) gene promoters plays a key role in their activation by the Oct-1-Vmw65 complex, but its role in mediating inhibitory effects of cellular octamer-binding proteins is less clear. We have used indicator viruses containing reporter constructs with different IE promoters driving a reporter beta-galactosidase gene within the viral genome to investigate this. We showed that deletion of the upstream IE promoter region containing the TAATGARAT motifs abolishes the inhibitory effect of the cellular octamer-binding proteins Oct-2.4 and Oct-2.5 on the viral IE promoter. This inhibitory effect can be restored by addition of a single TAATGARAT motif to the minimal promoter within the viral genome. Hence, the TAATGARAT motif can indeed mediate both positive and negative effects of cellular transcription factors when it is located within the viral genome.

Animals↗
PubMed1997

A Shannon entropy analysis of immunoglobulin and T cell receptor.

In 1970, before any antigen-bound immunoglobulin structure had been solved, Elvin Kabat proposed that regions of high amino acid diversity would be the antigen binding sites of immunoglobulin (Kabat, 1970). Conversely, sites of low variability were proposed to be structural, framework regions. This variability was defined by Wu and Kabat as the number of different amino acids found at a site divided by the relative frequency of the most common amino acid at that site (Wu and Kabat, 1970). Several groups have subsequently devised improvements of Kabat-Wu variability analysis (Litwin and Jores, 1992). While these methods are somewhat better than Kabat-Wu, they still suffer from Kabat-Wu's basic limitation: they account for only the most common one or two amino acids in estimating diversity. This leads to underestimates of low diversities and exaggerations of high diversities. Shannon information analysis eliminates serious bias and is more stable than Kabat-Wu and second generation measures of diversity (Jores et al. 1990; Wu and Kabat, 1970). Statistical reliability can be measured using Shannon analysis, and Shannon measurements can be provided with error estimates. Here we use Shannon's method to analyze the amino acid diversity at each site of T cell receptor Valpha and Vbeta to identify complementarity determining regions and framework sites. Our results reveal that the T cell receptor is significantly more diverse than immunoglobulin-suggesting T cell receptor has more than the previously-discovered four complementarity determining regions. These new complementarity determining regions may represent a larger antigen combining site, additional combining sites, or an evolutionary strategy to avoid inappropriate interaction with other molecules.

Animals↗
PubMed1997

Chlamydia trachomatis infection in prelabour amniorrhexis.

The prevalence of Chlamydia trachomatis in the lower genital tract and amniotic fluid of women with preterm prelabour amniorrhexis was assessed by DNA amplification for C. trachomatis performed in cervical swabs and amniotic fluid obtained by amniocentesis. C. trachomatis was present in the cervix of 20 (23%) of the cases and in six (30%) of those the organism was also present in the amniotic fluid. There was no association with other pathogens in the lower genital tract or amniotic fluid. The presence of C. trachomatis was not associated with a significant decrease in the amniorrhexis to delivery interval or with an increase in perinatal mortality or morbidity.

Amnion↗
PubMed1997

Wolfring dacryops and needling.

Cysts of the accessory lacrimal gland of Wolfring are uncommon in Europe; they are commoner in areas where trachoma is endemic and usually occur in eyes with some evidence of past trachomatous scarring (Bullock et al. 1986). The recommended mode of management is surgical, using an operating microscope, with an incision through the conjunctiva. Simple aspiration is inappropriate since the cyst refills. We describe a case of dacryops of the glands of Wolfring in a Caucasian male with no evidence of previous trachoma. This was managed with simple needling of the cyst. There was no recurrence of the cyst at 2 years follow-up.

Cysts↗
PubMed1997

Chemopreventive effect of difluoromethylornithine (DFMO) on mouse skin squamous cell carcinomas induced by benzo(a)pyrene.

The effect of the chemopreventive agent D,L-alpha-difluoromethylornithine (DFMO) on the incidence of skin squamous cell carcinoma was studied in SENCAR mice treated weekly with topical applications of benzo(a)pyrene (B(a)P) (0.15 mmol, 2 x /week) on the dorsal skin. Animals were randomized to receive either chow or chow supplemented with DFMO (1 g/1 kg) and studied at 10, 15, 20, 25, and 30 weeks of B(a)P treatment. Morphometric analyses at each timepoint evaluated the epidermal thickness (ET) and the number of epidermal nucleated layers (NL). The ET increased from 12-17 microns as early as 10 weeks after B(a)P treatment, reaching 22 microns at 20 weeks, and 27 microns at 25 weeks (130% increase). The NL also increased markedly. A relatively modest increase in ET was observed in animals treated with B(a)P and DFMO (16% at 15 weeks, 53% at 20 weeks, and 85% at 25 weeks) as compared to controls. The relative increase in NL showed a similar pattern. Although extensive epidermal hyperplasia was seen early, clear-cut focal premalignant lesions were not identifiable before week 20 of B(a)P treatment. At 20 weeks, the most frequently noted focal premalignant lesions in carcinogen-treated animals (without DFMO) were moderate dysplasias. At 25 and 30 weeks, a large increase was seen in the incidence of more advanced dysplastic lesions and invasive carcinomas. In the group treated with B(a)P and DFMO, a marked reduction in the number of carcinomas was observed at 25 and 30 weeks. At 25 weeks, DFMO reduced tumor yield from 5.8 to 3.2 carcinomas per mouse. At 30 weeks, the reduction was from 13.1 to 5.7 carcinomas per mouse (57% reduction). Collectively, these data emphasize the strong chemopreventive effect of DFMO against tumors in the mouse skin complete carcinogenesis model, as indicated by the reduction of overall skin tumor incidence and the decreased epidermal hyperplasia in DFMO-treated animals. Morphometrically defined increases in ET and NL can be used as early biomarkers of DFMO chemoprevention in mouse skin tumorigenesis.

Animals↗
PubMed1996

Cryopreservation of rat hepatocyte monolayer cultures.

1. Most previous attempts to cryopreserve hepatocytes have used suspensions stored at either -70 degrees C or in liquid nitrogen, and the major problem is that these do not, on subsequent thawing, attach well in culture. This limits their use in studies of drug metabolism and xenobiotic-induced toxicity. In this manuscript we demonstrate successful cryopreservation of rat hepatocytes as monolayers attached to a collagen film. 2. Monolayers can be frozen and thawed without significant loss of cells, and although damage to the internal and plasma membranes is evident immediately post-thaw, a remarkable repair process takes place over 24-48 h post-thaw. Immediately post-thaw only 10% of the cells exclude Trypan Blue, but by 48 h 80-90% of the thawed cells are viable, indicating that repair of the plasma membranes has taken place. 3. The cells post-thaw retain aspects of liver-specific function including cytochrome P450 content and albumin synthesis. However, cytosolic proteins are lost through the damaged membranes and, probably because of this, urea synthesis from ammonia is retained at only 25% of pre-freeze values. 4. A cryopreservation method based on adherent hepatocytes on a collagen substrate overcomes the problems encountered with culture of cryopreserved hepatocyte suspensions, and may provide a practical means of establishing a 'bank' of hepatocytes from several donors and species.

Albumins↗
PubMed1996

Environmental factors and nutritional status of rural children.

The nutritional status of school-aged children is a growing concern of health care professionals today. In collaboration with a Kellogg Project in the deep south, students from a large university school of nursing participated in a project to improve the nutritional status of rural school-aged children. The project goals focused on educating thd children about the U.S. Department of Agriculture (USDA) Food Guide Pyramid, reading nutritional labels and recognizing foods with high fat content, and the importance of exercise along with diet. The nursing students created a nutritional assessment tool to use with each child to determine their educational needs. The project involved lecture, interactive class discussion, and hands-on activities. Information from the assessment tool revealed that fast food and foods high in fat were the most popular with the children. After project completion, the posttest revealed an increase in cognitive knowledge of nutrition among all the children. In addition to this positive learning experience for the children, improving the health status of children in the community was an excellent educational opportunity for the nursing students.

Child↗
PubMed1996

Acute changes in handgrip strength, endurance, and blood lactate with sustained sport rock climbing.

BACKGROUND: Modern rock climbers stress the importance of hand-to-rock contact strength as a factor for success in competitive sport climbing events, however, the degree of handgrip fatigue that occurs during difficult climbing and the time course of recovery from fatigue have not been previously described. The purpose of this study was to characterize the nature of handgrip fatigue that results from difficult continuous climbing until a fall occurs. METHODS: Eleven expert-level rock climbers (age = 28.7 +/- 4.5 years) volunteered to climb continuous laps over a pre-set competition-type route on an indoor modular climbing wall until a fall occurred. The route difficulty (YDS rating of 5.12 a) was near the limit of each subject's "on-sight" lead climbing ability and placed an emphasis on physically difficult movements. "On-sight" refers to a climbing style where the climber ascends the route on the first try without falls and without prior viewing or information about the route. Practice was allowed to enable each subject to master the individual technical movements of the route. Fingertip blood samples were obtained 10 min pre-climb, at post-climb, and at 5-, 10-, and 20-min recovery and analyzed for lactate. Maximum handgrip force in Newtons was determined via dynamometry for each hand and averaged for pre-climb, post-climb, and 5-, 10-, and 20-min recovery periods. Right handgrip endurance, defined as the time that the dominant hand handgrip force could be sustained above 70 percent of handgrip strength, was determined pre-climb, post-climb, and at 20-min recovery. RESULTS: Mean climbing time during testing was 12.9 +/- 8.5 min for 2.8 +/- 2.2 laps over the route. Data among measurement times were analyzed using a repeated measures ANOVA with Newman-Keuls post hoc tests. Handgrip strength decreased by 22 percent and handgrip endurance decreased by 57 percent from pre-climb to post-climb and both remained depressed after 20 minutes of resting recovery. The pre-climb blood lactate of 1.4 +/- 0.8 mmol.l-1 significantly increased to 6.1 +/- 1.4 mmol.l-1 at post-climb and remained elevated (2.3 +/- 0.8 mmol.l-1) at 20-min recovery. Percent decreases in handgrip strength were significantly correlated with climbing time (R = 0.70), number of laps completed (R = 0.70), and blood lactate (R = 0.76). Percent decreases in handgrip endurance were significantly correlated with climbing time (R = 0.70) and number of laps completed (R = 0.80), but not with blood lactate (R = 0.56). CONCLUSIONS: It was concluded that handgrip strength and handgrip endurance decrease with continuous difficult rock climbing and remain depressed after 20 minutes of resting recovery. It also appears that handgrip strength recovers at a faster rate than handgrip endurance.

Accidental Falls↗
PubMed1995

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↗
PubMed1995

Association between high levels of ornithine decarboxylase activity and favorable prognosis in human colorectal carcinoma.

Several studies have documented increased expression of ornithine decarboxylase (ODC) in neoplastic colorectal tissue versus normal-appearing colonic mucosa. The present study was undertaken to determine whether there is an association between the degree of overexpression of ODC in colorectal carcinomas and survival in a series of 74 patients. A high level of tumor ODC expression was found to be significantly associated with greater survival in our patient series. Patients with tumor ODC activities greater than the median and especially in the highest quartile experienced a more favorable outcome than those patients with ODC values below the median or in the lowest quartile (P = 0.03 and 0.02, respectively). The presence of a GTP-activatable isoform of ODC was also significantly associated with a favorable prognosis but only in tumors of the right colon (P = 0.01). There was no association found between ODC activity and tumor grade, tumor size, or patient age, sex, or race. Our results demonstrate that high levels of ODC expression (and presence of a GTP-activatable isoform for right-sided colon tumors) predict a favorable prognosis in human colorectal carcinoma. Knowledge of a patient's ODC status at the time of surgery may be useful in decisions regarding adjuvant therapy. Understanding the mechanism(s) involved should lead to new therapeutic approaches for advanced colorectal carcinoma.

Aged↗
PubMed1994

Localization of transforming growth factor-alpha RNA and protein in the skin of psoriatic patients receiving therapy.

Fourteen patients with chronic plaque psoriasis requiring in-patient therapy were treated with a variety of antipsoriatic agents. All had four skin biopsies taken: two prior to therapy, one from a psoriatic plaque and one from adjacent clinically normal skin, and two further biopsies, one 2-3 weeks after starting therapy, and one at clinical clearance, taken from an area where there was previously a psoriatic plaque. In addition, three biopsies were taken from clinically normal skin of non-psoriatics. Transforming growth factor-alpha (TGF-alpha) RNA and protein distributions were estimated in these biopsies, using in situ hybridization with a cRNA TGF-alpha probe, and an antibody to TGF-alpha polypeptide. Prior to therapy, grain counts showed elevated levels of TGF-alpha RNA in the subcorneal layers of the epidermis. These levels decreased during clearance of the psoriasis. In one patient whose plaques did not clear, there was no decrease of TGF-alpha mRNA. Antibody studies showed the presence of TGF-alpha polypeptide in the epidermis prior to therapy, with a relative concentration of immunoprotein in the upper epidermal layers, compared with a more uniform distribution of immunoprotein after treatment, and in uninvolved skin of the same psoriatic patient. These studies extend our knowledge of the relationship between TGF-alpha and psoriatic skin.

Anthralin↗
PubMed1994

Assays to detect and characterize human immunodeficiency virus type 1 (HIV-1) receptor antagonists, compounds that inhibit binding of the HIV-1 surface glycoprotein, gp120, to the CD4 receptor on human T lymphocytes.

Human immunodeficiency virus type 1 infects human helper T lymphocytes by an interaction between gp120, the viral coat protein, and the T-cell receptor CD4. Two microtiter-based immunoassays, an enzyme-linked immunosorbent assay (ELISA) and a particle concentration fluorescence assay, were developed to measure gp120-CD4 binding and were then used to screen a variety of compounds for the inhibition of this interaction. Additional protocols, called "consumption assays," were defined to distinguish inhibitors which functioned by sequestering either gp120 or CD4 to prevent the final effective bimolecular interaction. Monoclonal antibodies of defined specificity and compounds known from other published studies to inhibit gp120-CD4 binding were tested in an attempt to validate the assays used in the study. Once the capacity of these assays to detect known gp120-CD4 inhibitors was confirmed, they were used to screen synthetic agents and fermentation broths for novel compounds that might be used as human immunodeficiency virus receptor antagonists. A 2,4-diaminoquinazoline, CP-101,816-1, was found to inhibit this interaction (50% inhibitory concentration in ELISA, 32.5 micrograms/ml) and to interact more strongly with CD4 than with gp120 in the consumption assays. The identification of a novel inhibitor, a 2,4-diaminoquinazoline, confirmed that such assays are useful for the detection of human immunodeficiency virus type 1 receptor antagonists.

Antibodies, Monoclonal↗
PubMed1993

A human tumor xenograft model of therapy with a bispecific monoclonal antibody targeting c-erbB-2 and CD16.

New strategies are required to clinically exploit the ability of monoclonal antibodies to target tumor for lysis by cellular effector mechanisms. In this report we examine the therapeutic effects of 2B1, a bispecific monoclonal antibody with specificity for the extracellular domain of the c-erbB-2 oncogene product and the human Fc gamma receptor, Fc gamma RIII (CD16), describe the characteristics and limitations of this model, and examine the mechanisms underlying the observed responses. The model uses SK-OV-3 human ovarian carcinoma xenografts in scid mice. These cells are susceptible to 2B1-directed lysis by human peripheral blood lymphocytes or lymphokine-activated killer cells, and maintain c-erbB-2 expression in vivo. 125I-labeled 2B1 selectively accumulates in tumor, with a peak of 10.5% injected dose/g of tumor 24 h following its i.v. injection. However, the selectivity of this binding is lessened by 2B1 accumulation in the lungs and other normal organs and persistence in the blood. This is caused by antibody binding to murine lung, colon, stomach, and skin expressing the epitope recognized by the anti-c-erbB-2 component of 2B1 in tumor-bearing, but not normal mice. In treatment studies using various permutations of antibody, human peripheral blood lymphocytes or lymphokine-activated killer cells and interleukin 2, cellular therapy alone had minimal effects on SK-OV-3 xenograft growth, but significantly improved when 2B1 treatment was incorporated. Median survivals increased from 80 +/- 3.5 days with no therapy to 131 +/- 7.3 days following therapy with 100 micrograms 2B1, interleukin 2, and human peripheral blood lymphocytes, with 70% of animals exhibiting no evidence of tumor at day 150. These effects were preserved when the cells were administered in human serum. In contrast, human serum abolished the antitumor effects of 520C9, which is the parent anti-c-erbB-2 antibody of 2B1. Thus 2B1-based therapy has therapeutic effects, without obvious toxicity, despite the targeting of this antibody to normal murine tissues. Since combinations of 2B1 and interleukin 2 may have antitumor properties, mechanisms other than bispecific monoclonal antibody-promoted conjugation of c-erbB-2 antigen-expressing tumor to CD16-expressing effector cells may be involved.

Animals↗
PubMed1993

Preservation of immune effector cell function following administration of a dose-intense 5-fluorouracil-chemotherapy regimen.

In a phase II clinical trial of 5-fluorouracil (5FU) plus N-(phosphonacetyl)-L-aspartate (PALA) therapy administration, a number of slowly developing clinical responses were observed. Because of this, a variety of immune parameters were sequentially studied in 21 patients on this trial. Of the 21 patients studied, 20 provided sufficient samples to compare baseline with subsequent values, 10 of the 20 patients responded to treatment. Responders and non-responders did not differ in any studied parameter at baseline. After 2 months of therapy, non-specific monocyte cytotoxicity (NSMC), antibody-dependent monocyte cytotoxicity (ADMC) and natural killer (NK) activity were higher in the entire study population, but these increases were not statistically significant. When responders and non-responders were evaluated separately, it was apparent that the trend was due solely to the changes observed in the responding patient population. When mean lysis values for each patient group were determined for each studied time point, it was possible to generate a mean area under the cytotoxicity/time curve (AUC) for each studied parameter. NSMC and ADMC did not differ in responders and non-responders. However, NK activity was significantly greater by mean AUC analysis (P = 0.006) in the responding group; NK activity was maintained in the responders, but decreased in non-responders. When lymphocyte and monocyte expression of the surface markers beta 2-microglobulin, HLA-DR, CD56, HNK-1, CD16 and interleukin-2 receptor were evaluated, there were no differences among responders and non-responders at baseline by mean AUC analysis or when comparing baseline with non-baseline values. It is concluded that although baseline immunological characteristics do not identify patients who are likely to respond to weekly 5FU and PALA, treatment is not associated with deleterious effects on the immune effector function parameters evaluated in this study, there being no effects on expression of a variety of associated cell-surface molecules.

Adenocarcinoma↗