Hypercalcaemia due to squamous cell carcinoma in a tuberculous kidney: case report and review of pathogenesis.
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Aged↗
Biomedical subjects
D Murphy
Publications and source records attributed to D Murphy.
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↗
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↗
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↗
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↗
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↗
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↗
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↗
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↗
Do formal advance directives affect resuscitation decisions and the use of resources for seriously ill patients? SUPPORT Investigators. Study to Understand Prognoses and Preferences for Outcomes and Risks of Treatments.
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Adult↗
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↗
Extrahypothalamic expression of the vasopressin and oxytocin genes.
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Animals↗
Regulation of the extent of polyadenylation of vasopressin and growth hormone mRNAs in response to physiological stimuli.
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Adenine↗
Enzymatic labeling of biologically active envelope glycoprotein gp120 of HIV-1.
We have found that the envelope glycoprotein gp120 of HIV-1 can be modified extensively by enzymatic oxidation of oligosaccharide chains without diminishing binding to its natural receptor, CD4. Using affinity purified galactose oxidase, over 20 sites per gp120 molecule were converted to chemically reactive aldehydes, as measured by 3H-BH4 reduction, while the conformation-dependent CD4 binding site remained intact. In contrast, periodate oxidation completely destroyed CD4 binding while producing fewer sites. Enzymatically labeled, biologically active gp120 should facilitate biochemical studies of receptor binding and viral inactivation by neutralizing antibodies.
Borohydrides↗
Neuron-specific expression and physiological regulation of bovine vasopressin transgenes in mice.
We have used transgenic mice to analyse the regulation of the bovine vasopressin (BVP) gene. We find that the restriction of BVP gene expression to anatomically and functionally distinct hypothalamic neuronal groups is achieved, in part, by selective repression. The expression of a 1.25 kb BVP proximal promoter, which on its own confers general expression of a reporter to most peripheral and brain tissues, was limited by sequences in the BVP structural gene to neural cells in the adrenal medulla and brain. Transgene expression in the hypothalamus was shown to be regulated by the physiological stimulus of dehydration in parallel with the endogenous gene. The expression of a larger 13.4 kb BVP transgene, containing 9 kb of 5' upstream sequence, the VP structural gene and 1.5 kb 3' of the transcription unit, was even more restricted and resembles that of the endogenous mouse gene. Hypothalamic expression of the 13.4 kb BVP transgene was regulated appropriately in response to an osmotic challenge.
Animals↗
Regulation of vasopressin gene expression: changes in the level, but not the size, of vasopressin mRNA following endocrine manipulations.
1. Regulatory interactions between the hypothalamoneurohypophyseal vasopressin (VP) axis and the endocrine systems of the anterior pituitary have been investigated in the rat by observing changes in VP mRNA expression following endocrine manipulations. 2. An increase in the level, but not size, of VP mRNA was found in the supraoptic (SON) and paraventricular nuclei (PVN) of the hypothalamus and in the neurointermediate lobe (NIL) of the pituitary following hypothyroidism (induced by drinking 6-n-propyl-2-thiouracil; PTU) and adrenalectomy. Hypothyroidism induced by alternative procedures (surgical thyroidectomy or PTU injections) did not exert similar effects. 3. Treatment with the dopamine agonist bromocriptine to reduce prolactin secretion raised levels of VP mRNA in the NIL only. Castration did not up-regulate VP mRNA levels. 4. Since the observed effects on VP mRNA levels occur in the absence of changes in plasma osmolality, these results provide evidence of nonosmotic regulation of VP gene expression, an effect which is observed most clearly in the NIL pool of VP mRNA. Furthermore, the effects are distinct from changes in VP mRNA levels associated with raised plasma osmolality since the VP mRNA size was not increased.
Adrenalectomy↗
Risk profile for Chlamydia infection in women from public health clinics in New York State.
The prevalence of chlamydial infection and associated risk factors were studied in 1531 women from ten clinics in New York State excluding New York City. Overall Chlamydia infection rates were 13.6%; 17.6% in eight high risk family planning and STD clinics, and 5.7% in two low risk college and private clinics. Risk factors for Chlamydia infection included: age < 20 years (odds ratio 1.6), use of oral contraceptives (odds ratio 2.0), a history of having more than one sexual partner (odds ratio 1.7) and, in one clinic where data was available, inflammation on Papanicolaou smears (odds ratio 2.1). These data helped secure funding for Chlamydia preventive services and permitted development of a risk profile (score card) of Chlamydia for each age group. Use of such a score card can be most helpful in assigning which patients could benefit most from Chlamydia cultures, especially in those areas where testing is unavailable or too costly to screen all patients.
Adolescent↗