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Biomedical subjects

D Murphy

Publications and source records attributed to D Murphy.

At least 109 records · Page 6Linked to original sources
PubMed1994

Audit of complete axillary dissection in early breast cancer.

The role of complete axillary dissection (CAD) in the management of breast cancer is controversial and largely unresolved. Acceptance of the results of trials incorporating CAD assumes that the axillary dissection is truly complete. To address this point, and also to define quality control criteria for this operation within our unit, we audited 100 consecutive axillary dissections as follows: the primary surgeon performed what he/she felt to be a thorough CAD and submitted separately the contents of level I, II and III for pathological evaluation; a second surgeon then independently assessed the dissection and arbitrarily labelled any further excised tissue as level IV. Level IV nodes were retrieved in 38% of cases. Tumour involvement of level IV nodes was noted in 5% (2/38) of dissections where lymph nodes were retrieved, but in neither instance was pathological staging altered. There was a significant decrease in the incidence of level IV node retrieval from 47% (28/60) in the first 6 months of audit to 20% (8/40) subsequently. This novel approach to our continuing audit identified quality control criteria for this procedure in our unit and suggested that audit of this kind benefits training.

Breast Neoplasms↗
PubMed1994

Immunohistochemical detection of mutant p53 protein in epithelial ovarian cancer using polyclonal antibody CMI: correlation with histopathology and clinical features.

Approximately 30-50% of cases of ovarian adenocarcinoma harbour mutations in the p53 tumour-suppressor gene associated with elevated levels of the protein detected by immunohistochemical staining. To investigate any relation between the presence of mutant p53 and clinicopathological features of disease, we examined a series of 50 cases of epithelial ovarian adenocarcinoma for expression of p53 by immunohistological staining on fixed, paraffin-embedded tissue sections using the polyclonal antibody CM1, and by direct nucleotide sequencing of polymerase chain reaction-amplified DNA from selected cases. Of the 50 cases examined, 28 (56%) were p53 positive and there was no significant correlation between p53 status and differentiation stage, clinical (FIGO) stage, multidrug resistance (mdr-1 P-glycoprotein) expression or response to treatment. However, we observed a statistically significant difference between the high prevalence of p53-positive serous tumours (18 out of 23) and the lower prevalence of p53-positive cases in mucinous tumours (3 of 12) suggesting that factors related to disease aetiology, associated with these histological subtypes, may determine the prevalence of functional inactivation of the p53 tumour-suppressor gene in ovarian adenocarcinoma.

Base Sequence↗
PubMed1994

Efficient and rapid affinity purification of proteins using recombinant fusion proteases.

In the affinity purification of recombinant fusion proteins, the rate-limiting step is usually the efficient proteolytic cleavage and removal of the affinity tail and the protease from the purified recombinant protein. We have developed a rapid, convenient and efficient method of affinity purification which can overcome this limitation. In one example of the method, the protease 3C from a picornavirus (3Cpro), which cleaves specific sequences containing a minimum of 6-7 amino acids, has been expressed as a fusion with glutathione S-transferase. The resultant recombinant 'fusion protease' cleaves fusion proteins bearing (from the amino-terminus) the same affinity tail as the fusion protease, a 3Cpro cleavage recognition site, and the recombinant protein of interest. The recombinant protein is purified in a single chromatographic step which removes both the affinity tail and the fusion protease. The advantages over existing methods include much improved specificity of proteolytic cleavage, complete removal of the protease and the affinity tail in one step, and the option of adding any desired amount of fusion protease to ensure efficient cleavage. The potential flexibility of the method is shown by the use of various affinity tails and alternative fusion proteases.

3C Viral Proteases↗
PubMed1994

Historical and contemporary correlates of syphilis and cancer.

BACKGROUND: This study examined the relationship between antecedent syphilis infection and cancer incidence in an attempt to identify specific cancer patterns. METHODS: The study cohort consisted of 16,420 people diagnosed with syphilis between 1972 and 1987 and who were residents of New York State, exclusive of New York City, at time of diagnosis. Incident cancers among cohort members were identified through linkage with files maintained by the New York State Cancer Registry. RESULTS: A total of 350 cancer cases were diagnosed among cohort members. For males and females combined, incidence was significantly elevated for cancers of the oral cavity standardized incidence ratio (SIR = 169, 95% confidence interval [CI]: 109-249), and specifically for cancer of the tongue (SIR = 251, 95% CI: 108-494). Significantly elevated incidence was observed among males for Kaposi's sarcoma (SIR = 2000, 95% CI: 1290-2950). CONCLUSION: While no conclusions may be reached concerning causality, the data do argue for increased cancer surveillance among people with syphilis. Moreover, findings are discussed in light of historical considerations.

Adolescent↗
PubMed1994

Mechanical lithotripsy.

Endoscopic lithotripsy is a procedure used for the removal of large stones in the common bile duct that cannot be removed after sphincterotomy. This procedure causes fragmentation of large stones, which allows easier retrieval of stones by other instruments such as balloons or baskets. There are currently two types of mechanical lithotripsy: one type uses an instrument called a mechanical lithotriptor, and the second type uses an electrohydraulic lithotriptor. This article focuses on mechanical lithotripsy. Since it is vital for the operator of this equipment to understand its function, assembly, disassembly, and maintenance, specific guidelines are provided.

Gallstones↗
PubMed1994

Cell specific expression of a vasopressin transgene in rats.

A transgene consisting of the rat vasopressin structural gene containing a reporter in exon III, flanked by 5 kb of upstream and 3 kb of downstream sequences, is expressed in vasopressinergic, but not oxytocinergic, magnocellular neurons of rats. Functionally appropriate physiological stimuli increase transgene expression in magnocellular neurons in an exaggerated fashion; the magnitude of the transgene response to osmotic challenge exceeds that of the endogenous gene by 10-15 fold. Magnocellular vasopressinergic neurons in the rat are now accessible to rational and precise genetic perturbation of function and regulation.

Animals↗
PubMed1994

The evidence for increasing cytotoxic dose intensity in the treatment of advanced ovarian cancer.

There is a body of conflicting evidence regarding the place of dose intense chemotherapy for advanced ovarian cancer. It remains unproven whether dose intensity is more important than total dose delivered, and measures of drug delivery to the tumour itself are absent or crude. There are various methods under evaluation for reducing the toxicity of chemotherapeutic drugs, thus enabling larger doses to be given. However, we must not lose sight of the fact that current treatment is palliative for the majority of women, making the quality of life an important issue. The place of dose intense cytotoxic chemotherapy, for the treatment of advanced ovarian cancer, must be evaluated in large, carefully designed, prospective trials which, if possible, should include a quality of life assessment.

Antineoplastic Agents↗
PubMed1994

Student experiential learning: a collaborative community practice project.

Theoretical and experiential learning in community assessment are essential components of the preparation of first-level community health nurses. This article describes a collaborative community practice project in which faculty incorporated senior baccalaureate community health nursing students as participants. Students assessed availability and utilization patterns of health care services in Spokane, Washington. Data derived from the survey were used by community planners in addressing issues of access to health care by low-income persons. Learning outcomes of this experiential process are described within the context of Burnard's Experiential Learning Model and community health nursing course objectives. Recommendations for design of similar experiential learning opportunities are made.

Clinical Competence↗
PubMed1994

Community analysis: a collaborative community practice project.

Lack of access to health care is a concern in many communities. A group of representatives from health, social service, other community agencies and nursing education meet regularly to address issues in providing care to homeless, low-income, and uninsured persons in Spokane, Washington. This group's efforts has been hampered by lack of clearly identified factors that adversely affect access to care. One aspect of community analysis performed by this group used a collaborative community practice model. Community diagnoses were determined from information collected from service providers. Community health nursing faculty, as clinical specialists, can play a role in such a collaborative process.

Community Health Nursing↗
PubMed1994

Prognosis-based futility guidelines: does anyone win? SUPPORT Investigators. Study to Understand Prognoses and Preferences for Outcomes and Risks of Treatment.

OBJECTIVE: Advocates for health care reform and others claim that significant savings could be achieved if "futile" care were eliminated. Our objective was to provide an initial estimate of the effects of a public policy that would preclude futile life-sustaining treatments, defined as those employed despite < or = 1% chance of surviving for 2 months. DESIGN: Simulation using data from an observational cohort study. SETTING: Five academic medical centers. PATIENTS: Seriously ill hospitalized adults enrolled in the Study to Understand Prognoses and Preferences for Outcomes and Risks of Treatment (SUPPORT). METHODS: We examined the impact of prognosis-based futility guidelines on survival and hospital length of stay on a cohort of seriously ill adults. We calculated the number of days of hospitalization that would not be used if, on the third study day, life-sustaining treatment had been stopped or not initiated for subjects with estimated 2-month survival probability of < or = 1%. RESULTS: Of the 4301 patients, 115 (2.7%) had an estimated chance of 2-month survival of < or = 1%. All but one of these 115 subjects died within 6 months. Almost 86% died within 5 days of prognosis. At the time of death, 92 subjects (80.0%) had had no attempt at resuscitation; 35 (30.4%) had had a life-sustaining mechanical ventilator withdrawn. A Do-Not-Resuscitate order was written either before (n = 61) or within 5 days (n = 18) of reaching this prognosis for 68.6% of the patients. These 115 subjects had total hospital charges of $8.8 million. By forgoing or withdrawing life-sustaining treatment in accord with a strict 1% futility guideline, 199 of 1,688 hospital days (10.8%) would be forgone, with estimated savings of $1.2 million in hospital charges. Nearly 75% of the savings in hospital days would have resulted from stopping treatment for 12 patients, six of whom were under 51 years old, and one of whom lived 10 months. CONCLUSIONS: Patients at a high risk of dying can be identified prospectively. Implementation of a strict, prognosis-based futility guideline on the third day of a serious illness would result in modest savings.

Adolescent↗
PubMed1994

Alternatively polyadenylated vasoactive intestinal peptide mRNAs are differentially regulated at the level of stability.

The role of cis-acting destabilizing RNA sequences in the determination of endocrine gene expression has been investigated using a novel paradigm, in which the differential regulation of two alternatively polyadenylated RNA transcripts may be observed both in vivo and in vitro. In the rat anterior pituitary gland in vivo, we have shown that, after the termination of an estrogen stimulus, a 1.7-kilobase (kb) vasoactive intestinal peptide (VIP) RNA containing an extensive 3'-untranslated region (UTR), is preferentially down-regulated with respect to a 1.0 kb VIP transcript that is uniquely abundant in this tissue. Differential regulation of the anterior pituitary VIP transcripts can be modeled in an explant culture system in which we defined both transcriptional and posttranscriptional phases of VIP gene regulation in vitro, and showed that selective down-regulation of the 1.7-kb transcript is posttranscriptional. Inhibitors of transcription and translation have also allowed us to show in vitro that differential regulation of VIP transcripts occurs through an active process that appears to involve the synthesis of a labile, destabilizing factor. In order to confirm the role of RNA destabilization as the primary mechanism of differential posttranscriptional regulation, we have also performed cell-free stability assays in which explant extracts were incubated with 32P-labeled run-off transcripts corresponding to the two alternatively polyadenylated VIP RNAs. The resultant estimates of RNA half-life showed significantly lower values for the synthetic VIP transcript containing the 3'-UTR. Our findings demonstrate the presence of functional destabilizing sequences in the 3'-UTR of the rat VIP RNA which appear to act in the physiological control of VIP gene expression.

Animals↗
PubMed1994

Expression of a rat vasopressin transgene in rat testes.

The rat vasopressin gene contains two transcriptional promoters; the activity of one is confined to the hypothalamus, while the other is testis specific. To define the sequences mediating the cell-specific expression of the vasopressin gene, we introduced rat vasopressin transgenes into the rat germ line. Neither transgene 1.5-V beta gal-0.2, which consists of the entire vasopressin structural gene containing a 3 kbp beta-galactosidase reporter element in exon III, flanked by 1.5 kbp upstream of the start of hypothalamic transcription and 0.2 kbp downstream of the polyadenylation site, nor transgene 3-V beta gal-0.2, which consists of the entire VP structural gene containing a 3 kbp beta-galactosidase reporter element in exon III, flanked by 3 kbp upstream of the start of hypothalamic transcription and 0.2kbp downstream of the polyadenylation site, were expressed in the hypothalamus. This contrasts with a previously described transgene consisting of the rat vasopressin structural gene containing a reporter in exon III, flanked by 5 kbp of upstream and 3 kbp of downstream sequences, which is expressed in vasopressinergic hypothalamic neurons. Both the 3-V beta gal-0.2 and 1.5-V beta gal-0.2 transgenes were expressed in testicular germ cells using a promoter located within the beta-galactosidase reporter element. Transgene RNA was most abundant during the late stages of meiosis. Rats bearing vasopressin-beta-galactosidase transgenes provide new models for the study of the mechanisms whereby an epigenetic choice is made between the use of a germ cell or a somatic promoter, and the stage-specific transcriptional regulation of a germ cell promoter during spermatogenesis.

Animals↗
PubMed1994

Over-expression of oxytocin in the testes of a transgenic mouse model.

The bovine oxytocin gene has been expressed in the testes of two independent transgenic mouse lines. Hybridization and RNase protection analysis showed that the oxytocin transgene was transcribed from the normal functional promoter in the Sertoli cells of the seminiferous tubules in a developmentally regulated manner. Immunohistochemistry indicated that both oxytocin and neurophysin epitopes were expressed together in the Sertoli cells at stages I-V and X-XII of the cycle of the seminiferous epithelium. Furthermore, analysis with high-performance liquid chromatography showed that there was a tenfold increase in the amount of amidated oxytocin present in testicular extracts from the transgenic mice. However, there appeared to be no detectable effect of this overproduction of hormone on testicular morphology or fertility parameters. A significant decrease by 50% was detected only in the levels of intratesticular testosterone and dihydrotestosterone. The results point to a local paracrine role for oxytocin in the modulation of Leydig cell function.

Animals↗
PubMed1994

Paediatric labelling requirements. Implications for pharmacokinetic studies.

The US Food and Drug Administration (FDA) has proposed new labelling regulations that describe alternative approaches for providing additional information to support labelling a drug, already approved for use in adults, for use in children. Therefore, the study of drugs in paediatric populations may now be encouraged. Paediatric pharmacokinetic studies are an important part of these trials. This action by the FDA may help resolve the ethical and technological concerns about the performance of clinical trials in children, and may render paediatric clinical trials more feasible. Most investigations in children are opportunistic in nature and their design is often constrained by a requisite noninvasive approach. Appropriately applied population-based techniques for both pharmacokinetic and pharmacodynamic data analysis may represent the most robust approach for generating a sufficiently large and accurate database for the use of new or old drugs in paediatric patients. Accordingly, this information, which is crucial for paediatric labelling of any drug product, must be obtained in infants and children if we are to truly individualize therapy for paediatric patients. The funding of 6 Pediatric Pharmacology Research Units by the US National Institutes of Health, and guidelines for application of pharmacokinetic methods to children may further contribute to the performance of paediatric clinical trials.

Aging↗
PubMed1993

Acute down-regulation of oxytocin and vasopressin mRNA levels following metrazole-induced seizure in the rat.

Following our recent demonstration of metrazole-induced immediate-early gene expression in the hypothalamic supraoptic nucleus (SON), we have now performed a mRNA and transcription analysis to determine the consequences of metrazole treatment for neurohypophyseal peptide gene expression in male rats. Levels of hypothalamic vasopressin (VP) and oxytocin (OT) mRNA were significantly reduced at 2 and 4 h after metrazole (50 mg/kg, i.p.), whereas pro-dynorphin mRNA was significantly elevated at 2 h. No changes in mRNA levels were found at 8, 24 or 48 h after treatment. Another convulsant (kainic acid, 8 mg/kg, i.p.) elicited similar effects on VP and OT mRNAs at 2 h. Specific analysis of the SON, following metrazole, revealed an equivalent effect on VP and OT mRNA levels but a nuclear run-on assay did not detect any change in SON VP gene transcription at 0.5, 1 and 2 h after treatment. The results provide evidence of a novel mechanism which may provide an additional level of control in the regulation of neuropeptide gene expression.

Animals↗