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Biomedical subjects

J Foley

Publications and source records attributed to J Foley.

At least 19 recordsLinked to original sources

The way forward for dental sedation and primary care?

OBJECTIVES: Firstly to determine the current provision of sedation in primary dental care in an area of Scotland without local secondary care support and secondly, to investigate dental practitioners' desire for formal postgraduate training in sedation techniques. DESIGN: A prospective postal questionnaire-based study. SETTING: Grampian Primary Care NHS Trust, UK, 2001. SUBJECTS: Questionnaires were sent to all NHS dental practitioners and community dental service clinicians (N = 194] employed through Grampian Primary Care NHS Trust, Scotland during March - April 2001. The questionnaires sought details about personal status and the use and perceived need for conscious sedation techniques in practice in addition to the stated desire for postgraduate training in sedation techniques. RESULTS: One hundred and thirty-six questionnaires were returned (70%). Forty-nine per cent of respondents reported current sedation use, with intravenous sedation the favoured technique (82%), followed by oral sedation (33%) and inhalation sedation (19%). Seventy-four per cent of participants considered that there was a need for sedation in their own practice and 68% were interested in further postgraduate training in sedation techniques. CONCLUSION: Nearly three-quarters of practitioners who responded felt that there was a need for sedation in their own practice, although less than half were able to offer sedation to their patients. Nearly 70% of practitioners felt there was a need for postgraduate training in sedation techniques.

Administration, Oral↗

Adenocarcinoma of the prostate: an expensive way to die.

The costs of radical prostatectomy and radiation therapy for localized carcinoma of the prostate are well known, the costs of terminal care for men with metastatic disease less so. We sought to determine the costs of terminal care incurred with prostate cancer in the last year of life. A retrospective chart review was conducted at five military medical centers identifying 32 patients who had died from prostate cancer from 1995 to 1997. The data investigated were: duration of metastatic disease, days hospitalized in the last year of life, palliative procedures (surgery or radiation), chemotherapy and need for transfusions. The mean duration of symptomatic metastatic disease was 3.4 y. The mean duration of hospitalization in the last year of life was 19 days. Seven patients (22%) required channel transurethral resection of the prostate (TURP). Three patients (9%) required either percutaneous nephrostomies or stenting. The mean number of transfusions required was 5.4. Eighteen patients (56%) underwent bilateral simple orchiectomy (BSO), 14 (44%) used LHRH agonists and 11 (34%) used anti-androgens. The mean total cost of hospitalization, studies, outpatient visits to physicians, palliative procedures and hormonal therapy was US dollars 24660 in the last year of life. Comparatively, the cost of radical prostatectomy is US dollars 12250 and three-dimensional conformal radiation therapy is US dollars 13823. Our estimation of costs due to metastatic disease is at best an underestimation. Men dying of prostate cancer incur significant costs in the last year of life. Based upon recent epidemiological data the cost of death due to prostate cancer in the US is over three quarters of a billion dollars a year.

Aged↗

Complete embedding and close step-sectioning of radical prostatectomy specimens both increase detection of extra-prostatic extension, and correlate with increased disease-free survival by stage of prostate cancer patients.

The objectives of this work were to evaluate the efficacy of controlled close step-sectioned and whole-mounted radical prostatectomy specimen processing in prediction of clinical outcome as compared to the traditional processing techniques. Two-hundred and forty nine radical prostatectomy (RP) specimens were whole-mounted and close step-sectioned at caliper-measured 2.2-2.3 mm intervals. A group of 682 radical prostatectomy specimens were partially sampled as control. The RPs were performed during 1993-1999 with a mean follow-up of 29.3 months, pretreatment PSA of 0.1-40, and biopsy Gleason sums of 5-8. Disease-free survival based on biochemical or clinical recurrence and secondary intervention were computed using a Kaplan-Meier analysis. There were no significant differences in age at diagnosis, age at surgery, PSA at diagnosis, or biopsy Gleason between the two groups (P<0.05). Compared with the non-close step-sectioned group, the close step-sectioned group showed higher detection rates of extra-prostatic extension (215 (34.1%) vs, 128 (55.4%), P<0.01), and seminal vesicle invasion (50 (7.6%) vs 35 (14.7%), P<0.01). The close step-sectioned group correlated with greater 3-y disease-free survival in organ-confined (P<0.01) and specimen-confined (P<0.01) cases, over the non-uniform group. The close step-sectioned group showed significantly higher disease-free survival for cases with seminal vesicle invasion (P=0.046). No significant difference in disease-free survival was found for the positive margin group (P=0.39) between the close step-sectioned and non-uniform groups. The close step-sectioned technique correlates with increased disease-free survival rates for organ and specimen confined cases, possibly due to higher detection rates of extra-prostatic extension and seminal vesicle invasion. Close step-sectioning provides better assurance of organ-confined disease, resulting in enhanced prediction of outcome by pathological (TNM) stage.

Adult↗

Cultural beliefs of Asian Americans associated with terminal illness and death.

OBJECTIVES: Cultural competence often focuses on the skills of the professional; whereas, this article focuses on the needs of the patient. DATA SOURCES: Research studies, review articles, book chapters, and clinical practice. CONCLUSIONS: Patients benefit from health care professionals that are attuned and able to nurture patients in a process of identifying their needs regarding terminal illness and death. The health care professional's ability and sensitivity to be culturally aware, knowledgeable, and open directly influences the patient's quality of life and death. IMPLICATIONS FOR NURSING PRACTICE: As the population becomes more diverse, health care professionals must develop cultural competence to add value to themselves, the profession of nursing, and health care in the future.

Asian↗

Loss of heterozygosity frequency at the Trp53 locus in p53-deficient (+/-) mouse tumors is carcinogen-and tissue-dependent.

Mutagenic carcinogens rapidly induced tumors in the p53 haploinsufficient mouse. Heterozygous p53-deficient (+/-) mice were exposed to different mutagenic carcinogens to determine whether p53 loss of heterozygosity (LOH) was carcinogen-and tissue-dependent. For 26 weeks, C57BL/6 (N4) [corrected] p53-deficient (+/-) male or female mice were exposed to p-cresidine, benzene or phenolphthalein. Tumors were examined first for loss of the wild-type p53 allele. p-cresidine induced p53 LOH in three of 13 bladder tumors, whereas hepatocellular tumors showed p53 LOH in carcinomas (2/2), but not in adenomas (0/3). Benzene induced p53 LOH in 13 of 16 tumors examined. Finally, phenolphthalein induced p53 LOH in all tumors analyzed (21/21). Analysis of the p-cresidine-induced bladder tumors by cold single-strand conformation polymorphism (SSCP) analysis of exon 4-9 amplicons failed to demonstrate polymorphisms associated with mutations in tumors that retained the p53 wild-type allele. p-cresidine induced a dose-related increase in lacI mutations in bladder DNA. In summary, these data demonstrate that loss of the wild-type allele occurred frequently in thymic lymphomas and sarcomas, but less frequently in carcinomas of the urinary bladder. In the bladder carcinomas other mechanisms may be operational. These might include (i) other mechanisms of p53 inactivation, (ii) inactivating mutations occurring outside exons 4-9 or (iii) p53 haploinsufficiency creating a condition that favors other critical genetic events which drive bladder carcinogenesis, as evidenced by the significant decrease in tumor latency. Understanding the mechanisms of p53 LOH and chemical carcinogenesis in this genetically altered model could lead to better models for prospective identification and understanding of potential human carcinogens and the role of the p53 tumor suppressor gene in different pathways of chemical carcinogenesis.

Alleles↗

Parathyroid hormone-related protein maintains mammary epithelial fate and triggers nipple skin differentiation during embryonic breast development.

Prior reports have demonstrated that both parathyroid hormone-related protein (PTHrP) and the type I PTH/PTHrP receptor are necessary for the proper development of the embryonic mammary gland in mice. Using a combination of loss-of-function and gain-of-function models, we now report that PTHrP regulates a series of cell fate decisions that are central to the survival and morphogenesis of the mammary epithelium and the formation of the nipple. PTHrP is made in the epithelial cells of the mammary bud and, during embryonic mammary development, it interacts with the surrounding mesenchymal cells to induce the formation of the dense mammary mesenchyme. In response, these mammary-specific mesenchymal cells support the maintenance of mammary epithelial cell fate, trigger epithelial morphogenesis and induce the overlying epidermis to form the nipple. In the absence of PTHrP signaling, the mammary epithelial cells revert to an epidermal fate, no mammary ducts are formed and the nipple does not form. In the presence of diffuse epidermal PTHrP signaling, the ventral dermis is transformed into mammary mesenchyme and the entire ventral epidermis becomes nipple skin. These alterations in cell fate require that PTHrP be expressed during development and they require the presence of the PTH/PTHrP receptor. Finally, PTHrP signaling regulates the epidermal and mesenchymal expression of LEF1 and (&bgr;)-catenin, suggesting that these changes in cell fate involve an interaction between the PTHrP and Wnt signaling pathways.

Animals↗

Black copper phosphate cement: does it have a future?

The aim of this study was to compare the in vitro compressive strength and solubility of a black copper cement with one established restorative material (a conventional glass ionomer cement) and two temporary restorative materials (a zinc phosphate and a zinc polycarboxylate cement). The mean compressive strength of black copper cement varied with the powder: liquid ratio, with an intermediate ratio having a comparable strength to that of the zinc polycarboxylate cement (the best material in this respect). The solubility of the black copper cement at all mixing ratios was significantly greater than that of all other test materials.

Algorithms↗

Referral of children to a general anaesthetic dental service in Tayside.

OBJECTIVE: To determine the adequacy of child referral for dental general anaesthesia (DGA) by local dental practitioners, given the recent guidance document to dentists from the General Dental Council and in addition, to determine the subsequent treatment and factors which influence treatment selection. DESIGN: A prospective study. SETTING: Department of Paediatric Dentistry, Dundee Dental Hospital, Dundee. SUBJECTS: Children [n = 84] who were referred for dental extractions under general anaesthetic over a three month period. RESULTS: Non-surgical dental extractions under general anaesthetic were requested in nearly 90% of referrals. In the majority of cases, the referral was deemed inadequate; e.g. the medical history was not mentioned in the majority of cases (85.7%) despite nearly one-fifth of patients having a relevant medical history. In general, referring practitioners under-estimated the extent of disease, requiring treatment plans to be changed in 76% of cases; all changes represented an increase in the number of dental extractions undertaken. The most common reasons for general anaesthetic use were: multiple dental extractions (73.8%); the patient's anxiety (63.1%); and patient's age (41.7%). As an alternative to general anaesthesia, treatment was undertaken successfully using inhalation sedation in nearly 15% of cases. CONCLUSION: Dental extractions under general anaesthetic are still a common reason for referral. Referring practitioners frequently provide inadequate information, in addition to under-estimating the treatment required. Alternative forms of anxiety management are available and should be considered for children requiring dental extractions.

Adolescent↗

Restoration of primary teeth: a study of copper phosphate cement.

OBJECTIVE: To determine the survival of 'PD' Black Copper Cement when used as a dental filling material in carious primary teeth. DESIGN: A prospective study. SETTING: Dundee Dental Hospital, Dundee. SUBJECTS: Fifty children with carious primary molars had 82 dental restorations placed in the initial study. For the follow-up study, 45 restorations were available. RESULTS: Over 65% of the Black Copper Cement restorations placed in the initial study failed. Modification of restoration technique reduced the total loss of filling material to 18% of cases. CONCLUSION: To take advantage of the cariostatic properties of black copper cement may require it to be used as a lining under a less soluble restorative material.

Child↗

Prostate cancer in men age 50 years or younger: a review of the Department of Defense Center for Prostate Disease Research multicenter prostate cancer database.

PURPOSE: Prostate cancer in men age 50 years or younger traditionally has accounted for approximately 1% of those diagnosed with prostate cancer. Prior studies of prostate cancer in men of this age led many clinicians to believe that they have a less favorable outcome than older men. Most of these studies were conducted before the advent of prostate specific antigen (PSA) screening programs. We evaluated a surgically treated cohort of men age 50 years or younger to determine whether disease recurred more frequently among them than in those 51 to 69 years old in the PSA era. MATERIALS AND METHODS: We reviewed the medical records of 477 men who underwent radical prostatectomy between 1988 and 1997. Age, ethnicity, preoperative PSA, clinical and pathological stage, margin and seminal vesicle involvement, and recurrence were compared between 79 men age 50 years or younger (study group) and 398, 51 to 69 years old (comparison group). Disease-free survival rates were compared using Kaplan-Meier and Cox regression techniques. RESULTS: There were 6 (7.6%) recurrences in the study group (79) and 107 (26.9%) in the comparison group (398). The disease-free survival curves were significantly different (log-rank p = 0.010). Age remained a significant prognostic factor (Wald p = 0.033) in multivariate Cox regression analyses that controlled for race, clinical and pathological stage, and pretreatment PSA. Similar results were found when the comparison group was limited to 116 patients 51 to 59 years old (log-rank p = 0.034, Wald p = 0.069). CONCLUSIONS: These data suggest that patients in the PSA era who underwent radical prostatectomy and were age 50 years or younger have a more favorable disease-free outcome compared to older men.

Adenocarcinoma↗

Improving the epilepsy service: the role of the specialist nurse.

There is currently a wide variation in the level of service provided for patients with epilepsy across the UK. Evidence is becoming available to suggest that improvements in local service provision may be achieved through the intervention of a specialist nurse. Using practical examples, this article explores the roles of the epilepsy specialist nurse, and examines how they may benefit patients and improve services. Functions such as liaison, patient assessment and management, counselling, provision of information, education, and audit are considered. It is hoped that the improved co-ordination and management of epilepsy services, that is achieved through specialist nurse intervention, will lead to improved patient outcomes and increased cost-effectiveness.

Epilepsy↗

CYP2C40, a unique arachidonic acid 16-hydroxylase, is the major CYP2C in murine intestinal tract.

We recently identified five different murine CYP2C cDNAs from a murine cDNA library. When expressed in a bacterial cDNA expression system, all five recombinant proteins metabolized arachidonic acid but produced distinctly different profiles. In addition, some CYP2C mRNAs were found in extrahepatic tissues, as well as in liver. Immunoblots with an antibody raised against recombinant CYP2C38, which recognizes all five murine CYP2Cs, demonstrated that among extrahepatic tissues, colon and cecum contained the highest amount of CYP2Cs. The highest concentration of CYP2Cs occurred in cecum and colon (cecum >/= proximal colon >> distal colon), with lower levels in duodenum, jejunum, and ileum. Immunohistochemical studies revealed that CYP2Cs were localized principally in epithelial cells and autonomic ganglia in gut and colon. Polymerase chain reaction amplification of reverse-transcribed mRNA using murine CYP2C-specific primers followed by cloning and sequencing identified CYP2C40 as the major CYP2C isoform expressed in murine intestinal tract. Recombinant CYP2C40 metabolized arachidonic acid in a regio- and stereospecific manner to 16(R)-HETE (hydroxyeicosatetraenoic acid) as the major product. To our knowledge, CYP2C40 is the first enzyme known to produce primarily 16-HETE. We conclude that CYP2C40 is one of the major cytochrome P450 proteins in the mouse intestinal tract. In the light of vasoactive and anti-neutrophilic effects of 16-HETE, we hypothesize that CYP2C40 may play an important role in endogenous biological functions in intestine.

Animals↗

Parathyroid hormone-related peptide stimulates proliferation of highly tumorigenic human SV40-immortalized breast epithelial cells.

Parathyroid hormone-related protein (PTHrP) is the main mediator of humoral hypercalcemia of malignancy (HHM) and it is produced by many tumors, including breast cancers. Breast epithelial cells as well as breast cancer tumors and cell lines have been reported as expressing PTHrP and the PTH/PTHrP receptor, suggesting that PTHrP may act as an autocrine factor influencing proliferation or differentiation of these cell types. We investigated PTHrP gene expression, PTH/PTHrP receptor signaling, and PTHrP-induced mitogenesis in three immortalized human mammary epithelial cell lines that exhibit differential tumorigenicity. The most tumorigenic cells expressed the highest levels of PTHrP messenger RNA (mRNA) and protein. We used reverse-transcription polymerase chain reaction (RT-PCR) and immunoblotting to detect the PTH/PTHrP receptor transcripts and proteins in all of the three cell lines. Treatment with human PTHrP(1-34) [hPTHrP(1-34)] and hPTH(1-34) increased intracellular cyclic adenosine monophosphate (cAMP) but not free Ca2+ in the nontumorigenic line. These agonists increased both cAMP and free Ca2+ levels in the moderately tumorigenic line, but only increased free Ca2+ in the highly tumorigenic line. Application of the PTH/PTHrP receptor antagonist [Asn10,Leu11,D Trp12]PTHrP(7-34) or PTHrP antibodies reduced [3H]thymidine incorporation in a dose-dependent fashion in the highly tumorigenic cell line but did not affect the other lines. Thus, treatment with a PTH/PTHrP receptor antagonist reduced cell proliferation, suggesting that PTHrP signaling mediated by the phospholipase C (PLC) pathway stimulates proliferation of a highly tumorigenic immortalized breast epithelial cell line.

Animals↗

Nateglinide alone and in combination with metformin improves glycemic control by reducing mealtime glucose levels in type 2 diabetes.

OBJECTIVE: To evaluate the efficacy and tolerability of nateglinide and metformin alone and in combination in type 2 diabetic patients inadequately controlled by diet, focusing on changes in HbA1c, fasting plasma glucose (FPG), and mealtime glucose excursions. RESEARCH DESIGN AND METHODS: In this randomized double-blind study, patients with an HbA1c level between 6.8 and 11.0% during a 4-week placebo run-in received 24 weeks' treatment with 120 mg nateglinide before meals (n = 179), 500 mg metformin three times a day (n = 178), combination therapy (n = 172), or placebo (n = 172). HbA1c and FPG were evaluated regularly, and plasma glucose levels were determined after Sustacal challenge at weeks 0, 12, and 24. Hypoglycemia and other adverse events were recorded. RESULTS: At study end point, HbA1c was reduced from baseline with nateglinide and metformin but was increased with placebo (-0.5, -0.8, and +0.5%, respectively; P < or = 0.0001). Changes in FPG followed the same pattern (-0.7, -1.6, and +0.4 mmol/l; P < or = 0.0001). Combination therapy was additive (HbA1c -1.4% and FPG -2.4 mmol/l; P < or = 0.01 vs. monotherapy). After Sustacal challenge, there was a greater reduction in mealtime glucose with nateglinide monotherapy compared with metformin monotherapy or placebo (adjusted area under the curve [AUC]0-130 min -2.1, -1.1, and -0.6 mmol x h(-1) x l(-1); p < or = 0.0001). An even greater effect was observed with combination therapy (AUC0-130 min -2.5 mmol x h(-1) x l(-1); P < or = 0.0001 vs. metformin and placebo). All regimens were well tolerated. CONCLUSIONS: Nateglinide and metformin monotherapy each improved overall glycemic control but by different mechanisms. Nateglinide decreased mealtime glucose excursions, whereas metformin primarily affected FPG. In combination, nateglinide and metformin had complementary effects, improving HbA1c, FPG, and postprandial hyperglycemia.

Aged↗

Activation of PTHrP gene expression in squamous carcinoma cell lines by mutant isoforms of the tumor suppressor p53.

We have evaluated the status of p53 expression in three squamous carcinoma cell lines that express high levels of PTHrP mRNA and protein and also cause hypercalcemia when grown in nude mice. All three of these lines possess a single p53 allele, each of which harbors a missense point mutation that gives rise to it mutant p53 protein with a denatured conformation. Using site-directed mutagenesis, we created a p53 expression construct bearing a missense mutation at codon 158, identical to that expressed by one of the cell lines. This construct and p53 constructs expressing representative denatured conformation mutants were then used to develop stably transfected lines, which expressed increased levels of PTHrP mRNA. Promoter-specific RNase protection indicated that this increase was due primarily to transcripts originating from the two TATA promoters, and not the GC-rich initiator element within the PTHrP gene. Cotransfection of mutant p53 expression vectors with a series of reporter constructs under the control of the human PTHrP promoter region showed that mutant p53 isoforms activated constructs containing multiple promoter elements and flanking sequences, but failed to activate constructs with individual promoters in isolation. These findings suggest that the activation of PTHrP gene expression by mutant p53 isoforms displaying a denatured conformation is dependent on interactions with sequences in the PTHrP gene regulatory region beyond the basal TATA promoters.

Alleles↗

Multicenter patient self-reporting questionnaire on impotence, incontinence and stricture after radical prostatectomy.

PURPOSE: We determined the incidence of patient self-reported post-prostatectomy incontinence, impotence, bladder neck contracture and/or urethral stricture, sexual function satisfaction, quality of life and willingness to undergo treatment again in a large multicenter group of men who underwent radical prostatectomy. We also determined whether the morbidities of sexual function satisfaction, quality of life and bladder neck contracture and/or urethral stricture are predictable from demographic and postoperative prostate cancer factors. MATERIALS AND METHODS: A self-reporting questionnaire was completed and returned by 1,069 of 1,396 eligible patients (77%) who underwent radical prostatectomy between 1962 and 1997. Of the respondents 868 (85.7%) underwent surgery after 1990 and in all prostatectomy had been done a minimum of 6 months previously. Questionnaire results were independently analyzed by a third party for morbidity tabulation and the association of patient reported satisfaction. RESULTS: The patient self-reported incidence of any degree of post-prostatectomy incontinence, impotence and bladder neck contracture or urethral stricture was 65.6%, 88.4% and 20.5%, respectively. The incidence of incontinence requiring protection was 33% and only 2.8% of respondents had persistent bladder neck contracture or urethral stricture. Although incontinence and impotence significantly affected self-reported sexual function satisfaction, quality of life and willingness to undergo treatment again (p = 0.001), 77.5% of patients would elect surgery again. This finding remained true even after adjusting for demographic variables, and the time between surgery and the survey by multiple logistic regression. CONCLUSIONS: Although radical prostatectomy morbidity is common and affects self-reported overall quality of life, most patients would elect the same treatment again. Impotence and post-prostatectomy incontinence were significantly associated with sexual function satisfaction, quality of life and willingness to undergo treatment again. Bladder neck contracture and/or urethral stricture was associated with willingness to undergo treatment again after adjusting for demographic variables and time from surgery to the survey.

Adult↗