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Biomedical subjects

D Murphy

Publications and source records attributed to D Murphy.

At least 271 records · Page 15Linked to original sources

Five year follow-up and dose delivery analysis of cisplatin, iproplatin or carboplatin in combination with cyclophosphamide in advanced ovarian carcinoma.

Eighty eight patients with FIGO stage IIb/c (postoperative residual) or III/IV epithelial ovarian cancer were randomised to receive cycles of cyclophosphamide (600 mg/m2) with either iproplatin (240 mg/m2), cisplatin (100 mg/m2) or carboplatin (300 mg/m2). A total of six cycles were given at monthly intervals. Patients were well-balanced for major prognostic factors. There was no significant difference in overall response rate (iproplatin arm, 64.3%, cisplatin arm 72.7% and carboplatin arm 66.7%). There were more complete remissions on the carboplatin arm, 45.8% compared with 21.4% on iproplatin and 22.7% on cisplatin but the difference was not statistically significant (p = 0.11). With a median follow up of 50 months the median survival for the iproplatin arm is 18 months, for the cisplatin arm 19 months and for the carboplatin arm 24 months (p = 0.15). Toxicity was greatest with cisplatin and least with carboplatin. Myelotoxicity limited the dose delivery of iproplatin as measured by total dose, dose intensity and dose intensity product. Carboplatin is at least as effective and less toxic than cisplatin when used in conjunction with cyclophosphamide for the treatment of ovarian carcinoma, and this analogue has been selected for dose intensification studies in this tumour at the Christie Hospital.

Adult↗

Hyperthyroidism, inappropriate plasma TSH and pituitary adenoma in three patients, two receiving long-term phenothiazine therapy.

Hypersecretion of TSH by a pituitary adenoma is thought to be a rare form of hyperthyroidism. We describe three such patients, each of whom presented with clinical hyperthyroidism and a diffuse goitre, without eye signs or dermatopathy. Two were receiving long-term phenothiazine, one of these was also acromegalic. Plasma thyroxine, free T4 and tri-iodothyronine were repeatedly raised in each; plasma TSH was grossly elevated in one and inappropriately normal in the other two. Plasma TSH did not rise in response to thyrotrophin-releasing hormone or metoclopramide and was not suppressed by L-dopa in any patient. Anti-thyrotrophin receptor antibodies were undetectable. Skull radiographs showed erosion and expansion of the pituitary fossa and CT scans confirmed a pituitary mass in each patient. A pituitary adenoma was removed by transphenoidal surgery in two patients and a TSH-secreting adenoma was confirmed by immunocytochemical staining and electron microscopy. Both patients were clinically euthyroid post-operatively but still had evidence of TSH excess. Pituitary surgery was technically unsuccessful in the third patient. Although two patients had hyperthyroidism of long duration, all three were diagnosed within one year of the introduction of a sensitive TSH assay to our laboratory. A TSH-secreting pituitary adenoma may be a more common cause of hyperthyroidism than has been believed.

Adenoma↗

Community health advocacy: primary health care nurse-advocate teams in urban communities.

In summary, our health advocacy program uses PHC teams in urban, underserved communities to deal with the interaction of social and health factors in solving problems related to access to appropriate (as perceived by residents) and affordable health care. This approach encourages grass-roots participation in problem identification and solution, a fundamental ingredient of community empowerment. Further, this program facilitates community identification of nurses as resource persons who encourage collaboration to improve the community's health status and as health providers who enhance the authority and autonomy of community participation in the resolution of health issues.

Community Health Nursing↗

Assessment of AIDS knowledge in selected New York State sexually transmitted disease clinics.

A 1988 survey regarding the level of knowledge about acquired immunodeficiency syndrome (AIDS) among 505 clients of sexually transmitted disease (STD) clinics demonstrated 80% correct responses. However, 13% thought AIDS could be transmitted via sharing utensils, and 51% were unaware that acquiring another STD could increase one's risk of human immunodeficiency virus (HIV) infection. In addition, only 10% always used condoms. An average 69% of patients obtained their AIDS information from newspapers, magazines, television, or radio; and 30% acquired information from medical or clinic staffs. In response to this survey, a videotape on AIDS was developed to show to patients of STD clinics while they are waiting to see a physician.

Acquired Immunodeficiency Syndrome↗

Human immunodeficiency virus 1. Predominance of a group-specific neutralizing epitope that persists despite genetic variation.

HIV-1 is known to show a high degree of genetic diversity, which may have major implications for disease pathogenesis and prevention. If every divergent isolate represented a distinct serotype, then effective vaccination might be impossible. However, using a sensitive new plaque-forming assay for HIV-1, we have found that most infected patients make neutralizing antibodies, predominantly to a group-specific epitope shared among three highly divergent isolates. This epitope persists among divergent isolates and rarely mutates, despite the rapid overall mutation rate of HIV-1, suggesting that it may participate in an essential viral function. These findings, plus the rarity of reinfections among these patients, suggest that HIV-1 may be more susceptible to a vaccine strategy based on a group-specific neutralizing epitope than was previously suspected.

CD4 Antigens↗

Cyclic nucleotide dynamics in the rat hypothalamus during osmotic stimulation: in vivo and in vitro studies.

The molecular mechanisms which regulate expression of vasopressin (AVP)- and oxytocin (OT)-encoding genes are unknown. We have investigated the regulatory role of one class of second messenger, the cyclic nucleotides, by examining levels of both adenosine 3',5'-monophosphate (cAMP) and guanosine 3',5'-monophosphate (cGMP) in hypothalamic nuclei of rats during osmotic stimulation. In vivo studies, in which rats were given 2% saline to drink for different periods (salt loading), demonstrated elevated levels of cAMP in the supraoptic nucleus (SON) after 2 days. Raised levels were also evident at 3 and 7 days. A similar (less marked) pattern was observed in the paraventricular nucleus (PVN) but not in the suprachiasmatic nucleus (SCN). cGMP was present at much lower levels than cAMP and did not exhibit parallel dynamics during salt loading; however, significant changes in cGMP levels were found in the SON and PVN. In vitro studies, in which explant cultures of punched hypothalamic nuclei were challenged with hypertonic media, demonstrated that increasing medium osmolality from 290 to 310 mOsm/kg doubled the level of cAMP in the SON but did not change levels in the PVN or SCN. A greater stimulus, 325 mOsm/kg, caused a 4-fold increase in SON cAMP, and small cAMP responses in the PVN and SCN. Marked cGMP responses were also observed in the SON following stimulation at 310 and 325 mOsm/kg, smaller responses being found in the PVN and SCN. These results are consistent with previous demonstrations of SON neuron osmosensitivity.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Independent regulation of neuropeptide mRNA level and poly(A) tail length.

Osmotic stimulation increases arginine-vasopressin (AVP) and oxytocin (OT) mRNA levels and poly(A) tail size concurrently. We now show that these changes are independently regulated. Whereas depletion of serotonin with p-chlorophenylalanine (PCPA) blocked the increase in hypothalamic levels of AVP and OT mRNA following osmotic stimuli in rats (2% saline drinking or dehydration), the increase in mRNA size was similar in PCPA and control animals. PCPA alone did not modify mRNA size. In addition to demonstrating an apparent obligatory role for serotonin in osmotically induced AVP and OT mRNA accumulation, the results provide evidence for different signaling pathways mediating transcript abundance and poly(A) tail length. Direct investigation of the regulatory mechanisms should be amenable to study in this system.

Animals↗

Diurnal rhythm of vasopressin mRNA species in the rat suprachiasmatic nucleus: independence of neuroendocrine modulation and maintenance in explant culture.

Vasopressin mRNA in the suprachiasmatic nucleus (SCN) of the rat brain exhibits diurnal variation in poly(A) tail length; a single species of mRNA identical in size to that in other hypothalamic nuclei is expressed in the light phase of the daily cycle whereas a second, smaller species is expressed in the dark phase. We have investigated the neuroendocrine factors which may regulate this rhythm by comparing vasopressin mRNA size with Northern analysis of RNA extracted from SCN tissue taken at 09.00 h (light phase) and 21.00 h (dark phase). The consistent rhythmic variation observed in normal male rats was not modified in either adrenalectomized or castrated animals or in ovariectomized female rats. The rhythm was also not disrupted following treatment with the serotonin-depleting agent parachlorophenylalanine, or following treatment with either melatonin or the benzodiazepine, triazolam. We next investigated whether the daily pattern of expression was maintained in isolated SCN. Microdissected blocks containing the paired SCN were explanted into culture at various times of the day for a period of 4 h. Vasopressin mRNA extracted from light phase cultures (11.00-15.00 h) exhibited no size change from control SCN mRNA taken at either 11.00 h or 15.00 h. In contrast, mRNA from cultures maintained over the period 16.00-20.00 h (lights off: 18.00 h) exhibited a marked size difference from 16.00 h controls, being similar to the smaller species observed in 20.00 h controls. Similarly, vasopressin mRNA from cultures maintained over the period 05.00-09.00 h (lights on 06.00 h) was similar in size to 09.00 h controls and contrasted to the pattern of expression observed in 05.00 h controls.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenalectomy↗

The use and misuse of domiciliary nebulizer therapy on the Isle of Wight.

Domiciliary nebulizer use is evaluated in a well-defined population on the Isle of Wight covering all ages. A questionnaire was administered to 167 known users and all were completed. The indication for nebulizer therapy was asthma (137), bronchitis (32) and emphysema (30). Twenty-three had never had a simple inhaler device prescribed and, of the others, 13 had never had instruction in its use. One hundred and fifty-three had used the nebulizer within the previous year and, of these, instruction was provided by physiotherapist (87), general practitioner (30), nurse (19) and hospital doctor (6). Nine received no advice. The drugs used comprised mostly salbutamol (140) and sodium cromoglycate (51). Twenty-six mixed medicines for use in the nebulizer and 24 admitted to exceeding the recommended dose. Twenty-three patients had a peak flow meter available at home. With treatment failure, 108 would call a doctor or report to hospital, while 25 would persist with nebulizer therapy. Thirty-two patients had no help at home in the event of an emergency. Most patients thought that they benefited greatly from nebulizer treatment at home, but better selection of patients and monitoring of treatment is needed. Comparison with previous studies suggests that there has been little improvement in the domiciliary use of nebulizers.

Adolescent↗

Vasopressin RNA in the neural lobe of the pituitary: dramatic accumulation in response to salt loading.

The peptides vasopressin (VP) and oxytocin are derived from preprohormone precursers encoded by highly homologous linked genes that are expressed in discrete groups of hypothalamic neurons. The mature hormones are released into the peripheral circulation from the neural (posterior) lobe of the pituitary and have also been implicated in the regulation of anterior lobe. We have used Northern blotting and in situ hybridization to RNA in tissue sections to describe the presence, anatomical localization, and regulation of VP and oxytocin RNAs in the pituitary gland itself. We were unable to detect VP transcripts in the anterior and intermediate lobes of the pituitary. Rather we found low levels of VP RNA in the neural lobe. Furthermore, the osmotic stimulation of a 2% (wt/vol) NaCl drinking diet resulted in a marked accumulation of VP RNA in the neural lobe. We suggest that VP, locally synthesized in pituicytes, may have paracrine effects on VP receptors in the neural lobe.

Animals↗

Effect of infusion rate of indomethacin on cerebrovascular responses in preterm neonates.

Cerebrovascular responses were studied in preterm infants by Doppler ultrasound and cerebral electrical impedance for one hour after intravenous indomethacin infusion for patent ductus arteriosus. Indomethacin in a dose of 0.2 mg/kg body weight was infused over five minutes in one group of infants (20 doses) and over 20 minutes in a second group of infants (16 doses). There were no significant differences between the two groups in birth weight (mean = 1068 g, range 569-1950), gestational age (mean 28.4 weeks, range 25-31), or postnatal age (mean 18.1 days, range 6-42). There was a significant reduction in both the Doppler mean flow velocity in the anterior cerebral artery (mean (SE) -20 (4.2)%) and peak amplitude of cerebral electrical impedance (-26 (3.9)%) within two minutes of starting the indomethacin infusion over five minutes. There was no significant change after the infusion over 20 minutes. There were no significant changes in blood pressure or carbon dioxide tensions after infusion at either rate. The results suggest that infusion of indomethacin over five minutes caused a potentially deleterious reduction in cerebral blood flow. No such reduction occurred when it was infused over 20 minutes.

Blood Flow Velocity↗

Identification of an immunodominant region on the I-A beta chain using site-directed mutagenesis and DNA-mediated gene transfer.

To identify which polymorphic residues determine the allospecific antibody binding sites on A beta polypeptides, mutant Ak beta genes were constructed encoding single or multiple amino acids of the d allele at 14 polymorphic positions in the beta 1 domain. Cell lines expressing these genes were analyzed by quantitative immunofluorescence using 16 mAbs reactive to Ak beta or Ad beta. Substitution of d allele residues at positions 63 and 65-67 in the Ak beta polypeptide resulted in the loss of binding of all Ak beta-reactive antibodies and the gain of binding of most Ad beta-reactive antibodies. Two Ad beta-reactive mAbs bound to the mutant Ak beta polypeptide containing d allele-characteristic residue at position 40. In contrast, substitution of the other polymorphic residues in the NH2-terminal and COOH-terminal regions of the beta 1 domain did not alter antibody binding.

Amino Acid Sequence↗

A morphological analysis endocrine tumour genesis in pancreas and anterior pituitary of AVP/SV40 transgenic mice.

Insertion into the mouse genome of the hybrid oncogene made up of bovine vasopressin gene derived 5' upstream sequences and the coding sequences of SV40 large T-antigen promoted tumours in anterior pituitary and endocrine pancreas of mice bearing this transgene. In order to investigate the morphology of the steps in the neoplastic process, we used light and electron microscopy to study these organs in 42 animals belonging to the 3rd, 4th and 5th generations, subdivided into 4 age groups from 20 days to 100 days of life. Antibodies to large T-antigen were used to identify sites of expression of the hybrid oncogene, thus monitoring the steps in neoplastic transformation. Large T-antigen immunoreactivity was identified in dysplastic lesions of younger animals and in both dysplastic lesions and tumours of older mice. Insulin (100% of cases) and pancreatic polypeptide (25% of cases) immunoreactivities were revealed in pancreatic lesions but no hormonal immunoreactivity was detected in the pituitary lesions. The ultrastructural study confirmed that the majority cell population of the pancreatic neoplasms was B-type and that the anterior pituitary tumours were poorly granulated. The subcellular localization of large T-antigen immunoreactivity was investigated by the immunogold method and was confined to the heterochromatin of tumour cell nuclei. These findings provide evidence for the dysplasia-neoplasia sequence in the genesis of endocrine tumours of pituitary and pancreas of transgenic mice. The vasopressin-SV40 large T-antigen transgenic mice may therefore be an useful model for the study of endocrine cell oncogenesis.

Animals↗

Aspects of instrumentation design for impedance imaging.

This paper takes the circuit for a general purpose impedance imaging data measurement system and analyses the importance of several components. For high accuracy it is shown that stray capacitances in the input circuitry are the major problem although the use of a phase sensitive demodulator can minimise this problem. It is shown that harmonic distortion in the constant current generator can cause errors which are, however, reduced if a linear multiplying demodulator is used rather than a switching demodulator.

Mathematics↗

Analysis and assessment of errors in a parallel data acquisition system for electrical impedance tomography.

Three possible data collection configurations for electrical impedance tomography are considered. These are serial current but parallel voltage measurement or full parallel operations. Measurement errors due to stray capacitances, common mode signals and contact impedance are considered. It is concluded that a parallel system offers advantages in terms of either speed or signal to noise ratio by may give larger common mode errors.

Electric Conductivity↗