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R Murphy

Publications and source records attributed to R Murphy.

At least 37 records · Page 2Linked to original sources
PubMed1990

Pharmacologic profile of a low molecular weight heparin (enoxaparin): experimental and clinical validation of the prophylactic antithrombotic effects.

Some 10 low molecular weight heparin products are currently available for commercial use. Enoxaparin and fraxiparin appear to be the most developed low molecular weight heparins. Many well-designed clinical trials have been carried out for different clinical indications with both of these products. As shown in both experimental and clinical settings, the prophylactic antithrombotic efficacy of enoxaparin is distinct from other low molecular weight heparins. Enoxaparin has provided consistently impressive clinical results. Moreover, at comparable dosages, other products have exhibited safety/efficacy profiles different from that of enoxaparin. The clinical performance of each low molecular weight heparin is characteristic of only that particular agent. Besides the commercially available low molecular weight heparin preparations, some 14 other agents are under development at this time. Although each product has similar basic characteristics, their biological actions should be studied carefully. Apart from differences in the physicochemical properties, the pharmacologic actions of these agents may differ significantly. Only results from valid clinical trials will show similarities or differences between the low molecular weight heparins. Other manufacturers should follow the lead of enoxaparin and conduct their own clinical trials on each of their products.

Animals↗
PubMed1989

Analogues of vasoactive intestinal peptide (VIP) contract the guinea-pig uterine artery but do not antagonize VIP-induced relaxations.

Guinea-pig vasoactive intestinal peptide (gpVIP-(1-28] in the concentration range 3 x 10(-9)-3 x 10(-7) mol.1-1 relaxed precontracted segments of the guinea-pig uterine artery. Porcine VIP-(10-28) (pVIP-(10-28], [4-Cl-D-Phe6,Leu17]VIP, or [N-Ac-Tyr1, D-Phe2]GRF-(1-29)-NH2 did not antagonize VIP-induced relaxations of the artery, but high concentrations of the two VIP analogues produced large, transient contractions of the artery. In some preparations 10(-5) mol.1-1 gpVIP-(1-28) also caused transient arterial contractions. These data indicate the presence of two distinct receptors for VIP on the guinea-pig uterine artery, mediating opposite effects on vascular tone.

Animals↗
PubMed1989

Projections of neurons with neuromedin U-like immunoreactivity in the small intestine of the guinea-pig.

Neuromedin U immunoreactivity was located histochemically in the guinea-pig small intestine. Projections of immunoreactive neurons were determined by analysing patterns of degeneration following nerve lesions. The co-localization of neuromedin U immunoreactivity with immunoreactivity for substance P, neuropeptide Y, vasoactive intestinal peptide and calbindin was also investigated. Neuromedin U immunoreactivity was found in nerve cells in the myenteric and submucous plexuses and in nerve fibres in these ganglionated plexuses, around submucous arterioles and in the mucosa. Reactive fibres did not supply the muscle layers. Most reactive nerve cells in the myenteric ganglia had Dogiel type-II morphology and in many there was co-localization of calbindin, although some Dogiel type-II neuromedin U neurons were calbindin negative. Lesion studies suggest that these myenteric neurons project circumferentially to local myenteric ganglia. Projections from myenteric neurons also run anally in the myenteric plexus, while other projections extend to submucous ganglia, and still further projections run from the intestine to provide terminals in the coeliac ganglia. In the submucous ganglia neuromedin U was co-localized in three populations of nerve cells: (i) those with vasoactive intestinal peptide immunoreactivity, (ii) neurons containing neuropeptide Y, and (iii) neurons containing substance P. Each of these populations sends nerve fibres to the mucosa. Neuromedin U immunoreactivity is thus located in a variety of neurons serving different functions in the intestine and therefore probably does not have a single role in intestinal physiology.

Animals↗
PubMed1989

Measurement and chromatographic characterization of prodynorphin-derived peptides in the guinea-pig ileum.

Guinea-pig ileum was dissected and the mucosa, submucosa and external musculature extracted with aqueous acetic acid for measurement of four prodynorphin-derived peptides, namely dynorphin A 1-8, dynorphin A 1-17, dynorphin B, and alpha-neoendorphin. The peptide-like immunoreactive material extracted from the external musculature was characterized by multi-dimensional chromatographic analysis and compared to synthetic porcine standards. The chromatographic methods utilized were: reversed-phase high performance liquid chromatography (RP-HPLC), using two different eluants; cation exchange high performance liquid chromatography (CE-HPLC) and gel filtration chromatography. The dynorphin A 1-8-like immunoreactive material was homogeneous and coeluted with the standard in all chromatographic modes. The dynorphin A 1-17-like and dynorphin B-like immunoreactive material was heterogeneous but showed a peak that coeluted with synthetic standard in all chromatographic modes. The alpha-neoendorphin-like immunoreactive material also appeared to be heterogeneous with the major component on CE-HPLC coeluting with the synthetic peptide standard while the major component on RP-HPLC eluted differently. It was concluded that the guinea-pig ileum contains immunoreactivity for peptides derived from all coding regions of the prodynorphin gene and that these peptides may be present in multiple immunoreactive forms.

Animals↗
PubMed1989

Correlated functional and structural analysis of enteric neural circuits.

Views about the roles and nature of the enteric nervous system have changed dramatically in the last ten years. This system of neurons is recognized to control, through reflex pathways intrinsic to the gut wall, motility, transport of water and electrolytes, and blood flow in the small and large intestines. There are thus a range of neuron types in the enteric nervous system, including sensory neurons, motor neurons, and interneurons, involved in the control of each of these functions. The present paper deals with the recent efforts to provide an integrated functional and structural description of the nerve circuits. One of the challenges in this quest has been to identify primary sensory neurons and final motor neurons involved in motility control. Evidence is presented that in the guinea-pig small intestine the primary sensory neurons have Dogiel type II morphology and are, electrophysiologically, AH neurons. They send circumferential processes to adjacent myenteric ganglia and some of them, at least, have processes leading from the mucosa. Motor neurons are S neurons, with cell bodies in the myenteric plexus. Those that supply the circular muscle are Dogiel type I neurons and provide processes that run circumferentially for about one third of the circumference of the intestine. The circuits for secretomotor reflexes have been partly worked out. The secretomotor neurons have cell bodies in the submucous ganglia and are activated to return water and electrolytes to the lumen during digestion. The secretomotor reflexes are regulated, in accord with whole body water and electrolyte homeostasis, via sympathetic neurons which lower the excitability of secretomotor neurons.

Animals↗
PubMed1989

Campylobacter pylori in patients with dyspeptic symptoms and endoscopic evidence of erosion(s).

The relationship between Campylobacter pylori (CP), histologic gastritis, and dyspeptic symptoms is becoming gradually clearer, but there is still a lack of knowledge of the natural history of treated or untreated gastritis. We examined serial biopsies from the gastric fundus, body, and antrum, and from the duodenum in 16 dyspeptic patients. Patients with concomitant peptic ulcers, alcoholism, or nonsteroidal anti-inflammatory drug use were excluded. CP was present in the biopsies of 50% of patients at presentation. When CP was present, the antrum was always infected, and often had the highest density of organisms. In the duodenum, CP was found only in areas of gastric metaplasia. The presence of CP was highly correlated with gastritis activity (neutrophilic infiltrate). A 4-yr follow-up study of symptoms, endoscopic appearance, and histologic findings including the presence of CP was performed in 10 of the original 16 patients. After 4 yr, both the severity and frequency of epigastric pain remained the same in seven patients, worsened in one, and improved in two. All patients who had CP at initial presentation retained the organism (5/10), whereas none of the previously noninfected patients acquired the infection (5/10). Both CP-positive and -negative patients were treated for 3 wk with 524 mg bismuth subsalicylate qid, and for the first 2 of 3 wk with 250 mg metronidazole qid. One patient who was CP positive was lost to follow-up. In three of the remaining four patients on this regimen, the organism was eradicated. Of the nine patients who completed the treatment program, two had no change in symptoms and seven improved. CP was present in three of seven with improved symptoms and in one of two with no change in symptoms. After treatment, the only change in histology was the disappearance of activity in the CP-positive patients who lost the organism. In conclusion, CP was present in 50% of dyspeptic patients with endoscopic evidence of at least one erosion. Both the symptoms and CP persisted for 4 yr. Dyspeptic symptoms improved after bismuth subsalicylate/metronidazole therapy, regardless of the presence or absence of CP, although the regimen did succeed in eradicating the organism in three of the four CP-positive patients who completed the study.

Adolescent↗
PubMed1988

Evidence that neuropeptide Y released from noradrenergic axons causes prolonged contraction of the guinea-pig uterine artery.

The participation of neuropeptide Y (NPY) in transmission from sympathetic vasoconstrictor neurons was investigated in the guinea-pig uterine artery, where NPY has been demonstrated immunohistochemically in noradrenergic axons. Exogenous NPY produced long-lasting contractions of isolated arterial segments at low resting tone. Low concentrations of NPY (10(-8)-3 X 10(-7) mol.l-1) were more potent than equimolar concentrations of noradrenaline (NA). NPY produced concentration-dependent desensitization to further application of NPY, but did not affect the magnitude of NA contractions. Trypsin (1.4-2 micrograms.ml-1) reduced NPY-induced contractions by 80-100%, but did not alter NA-induced contractions. Transmural electrical stimulation of arterial segments, after surgical removal of vasodilator axons, produced biphasic contractions which were abolished by guanethidine. Prazosin abolished the fast phase of the neurogenic contraction, leaving a slow contraction with a time course similar to that produced by a low concentration of NPY. The slow contraction was more pronounced at higher frequencies of stimulation (15-20 Hz) than at lower frequencies, and was selectively reduced after desensitization produced by NPY (10(-5) mol.l-1), or after exposure to trypsin. These results suggest that sympathetic vasoconstriction of the guinea-pig uterine artery is produced by release of both NA and NPY from noradrenergic axons.

Animals↗
PubMed1988

Antibody reactivity with HBLV (HHV-6) in U.S. populations.

500 sera representing healthy blood donors and a random representation of the U.S. population collected 10 years ago were screened by ELISA for antibody reactivity with purified, disrupted HBLV virions. In each group, the ELISA results were normally distributed with no evidence of bimodality. All sera were subsequently retested after preincubation of each with well-characterized preparations of disrupted HSB-2 cells or HBLV-infected HSB-2 cells. Sera showing significant levels of HBLV-specific neutralization (50% or more) were found in Minneapolis, Kansas City, and in a random population survey (81, 88 and 97% of donors, respectively). Mean ELISA test values were the same for all groups and for males and females within the same group. Sera from these normal donors reacted preferentially with viral antigens of 120 and 58 kDa by Western blot. In a hospital-based prevalence study, frequent IgM and IgG seroconversions were apparent among infants less than 1 year old, and mean ELISA test values reached the adult level before school age. Antigen preparations used in blocking experiments showed no competitive cross-reactivity with antisera against EBV, CMV, HSV, VZV, HIV, or adenovirus type 2 at levels which reduced antibody binding to HBLV by more than 90%. Antibody cross-reactivities towards HBLV and other human herpesviruses were assessed by cross-correlation of viral antibody titers against all of the viruses and by cross-absorptions of antisera against the other viruses with HBLV. In these experiments no antibody cross-reactivity between HBLV and other human herpesviruses were detected. The significance of these findings with respect to health/disease status is presently unknown. Further seroepidemiologic studies of quantitative levels of HBLV antibody reactivity to measure the age of primary infection and progressive changes in healthy and selected disease populations are needed to determine the risk of disease associated with HBLV infection.

Adolescent↗
PubMed1988

Bioavailability of low-dose vs high-dose 6-mercaptopurine.

The bioavailability of oral 6-mercaptopurine (6MP) at standard doses is very low, largely as a result of extensive first-pass metabolism by xanthine oxidase. Fewer than one third of patients achieve 6MP plasma concentrations known to be cytocidal in vitro (greater than 1 mumol/L). Studies in vitro have suggested that first-pass metabolism can be saturated at higher doses of 6MP. To determine whether saturation occurs in vivo at clinically used doses and whether bioavailability can be enhanced by increasing the dose, the bioavailability of different doses of 6MP was studied first in rhesus monkeys and then in children with acute lymphoblastic leukemia in remission. In monkeys a higher dose of 6MP resulted in enhanced bioavailability, whereas in patients the mean relative bioavailability at the higher dose was significantly less. However, all patients achieved cytocidal (greater than 1 to 10 mumol/L) plasma concentrations at the higher dose without manifesting significant clinical toxicity. Therefore cytocidal levels of 6MP can be achieved in patients with oral 6MP without the risk of unexpectedly high levels caused by saturation of first-pass metabolism.

Adolescent↗
PubMed1988

Inhibition of bacterial colonization by antimicrobial agents incorporated into dental resins.

The antimicrobial activity of several chemical agents was determined by incorporating these agents into dentine adhesive resin and following the colonization of Streptococcus mutans on the surfaces of the resin and culture vessel, as well as in the surrounding medium, by optical density measurements. It was found that sodium fluoride and dodecylamine, an organic amine, exhibited excellent antimicrobial properties. These chemicals not only inhibited bacterial growth completely but also seemed to reduce the adhesion of the bacteria to the resin surface. A silver compound, protargin, was mildly effective in inhibiting growth of S. mutans. Copper oxide and chelating acids such as vanillic acid, syringic acid, and ethylenediamine-n, n' diacetic acid (EDDA) were not effective as antimicrobial agents against S. mutans.

Amines↗
PubMed1987

Epidemiological assessment of the health and nutrition of Ethiopian refugees in emergency camps in Sudan, 1985.

The findings from epidemiological data that were collected from emergency camps for Ethiopian refugees during a mass influx of refugees into Eastern Sudan in 1985 are presented. An overall mortality of 8.9 per 10,000 a day was recorded during February 1985, and in children under 5 years of age the rate was 22 per 10,000 a day. The estimated prevalence of malnutrition (calculated as less than 80% of the reference weight for height) ranged from 32% to 52% among children of preschool age. The principal causes of morbidity and mortality were measles, diarrhoea and dysentery, respiratory infections, and malaria. The findings suggest that malnutrition and disease increased in these refugees after they arrived in the camps. Epidemiological assessment is essential to help to maintain the health and nutrition of refugees in emergency camps.

Adolescent↗
PubMed1987

Pathway-specific connections between peptide-containing preganglionic and postganglionic neurons in the vagus nerve of the toad (Bufo marinus).

We have examined immunohistochemically the distribution of postganglionic nerve cell bodies and their preganglionic inputs in the vagus nerve of the toad, Bufo marinus. Nerve cell bodies containing immunoreactivity (IR) to somatostatin (SOM) were found at the origin of the oesophago-gastric ramus; these neurons projected to the lung. Cell bodies with SOM-IR also occurred in the intracardiac branches of the vagus, but were absent from the distal segments of the pulmonary and oesophageal rami of the vagus. Cell bodies with IR to vasoactive intestinal peptide (VIP) also occurred at the origin of the oesophago-gastric ramus, but most of these neurons projected to the oesophagus. Most neurons in the distal pulmonary and oesophageal rami were VIP-IR. Some nerve cell bodies in the vagosympathetic trunk and in the intracardiac rami contained both SOM-IR and VIP-IR. Vagal preganglionic nerve fibres with IR both to a somatostatin-like peptide and to substance P were associated exclusively with those postganglionic VIP-IR neurons that projected to the oesophagus. These results provide evidence for highly specific connections between immunohistochemically defined populations of preganglionic and postganglionic neurons in the vagus nerve.

Animals↗
PubMed1987

Management of intraocular pressure during cardiopulmonary bypass.

Intraocular pressure was measured in two groups of patients undergoing cardiopulmonary bypass surgery. A control group received mannitol at the start of bypass in accordance with standard practice; pressure was found to rise by 6.4 mmHg. In a second group of patients mannitol was administered 30 min prior to bypass; pressure elevation of 2.4 mmHg was found. These findings are discussed in relation to other clinical observations during bypass and to ocular morbidity complicating bypass surgery.

Cardiopulmonary Bypass↗
PubMed1986

Neuropeptide Y-like immunoreactivity is absent from most perivascular noradrenergic axons in a marsupial, the brush-tailed possum.

Noradrenergic perivascular axons were demonstrated in all systemic arteries and veins of a marsupial, the brush-tailed possum (Trichosurus vulpecula), by a catecholamine fluorescence procedure and with antisera directed against the catecholamine-synthesizing enzymes tyrosine hydroxylase (TH) and dopamine-beta-hydroxylase (D beta H). Perivascular axons with neuropeptide Y-like immunoreactivity (NPY-LI) were not found in most systemic arteries and veins using antisera which recognize NPY and other members of the pancreatic polypeptide family in diverse vertebrate species. The exceptions were the renal, coeliac, main mesenteric and iliac arteries, where up to 50% of axons with TH-LI or D beta H-LI also showed NPY-LI with two of the 4 antisera used. No noradrenergic nerve cell bodies in thoracic sympathetic ganglia had NPY-LI, whilst 3% of noradrenergic nerve cell bodies in lumbar sympathetic chain ganglia had weak NPY-LI. This marsupial is the first vertebrate species found to date in which the majority of perivascular noradrenergic axons do not contain NPY-LI. If these axons contain an as yet unidentified neuropeptide, it is unlikely to be closely related to NPY.

Animals↗