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Biomedical subjects

R Murphy

Publications and source records attributed to R Murphy.

At least 55 records · Page 3Linked to original sources

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

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

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

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

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

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

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

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

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

Innervation of the large arteries and heart of the toad (Bufo marinus) by adrenergic and peptide-containing neurons.

The innervation of the major arteries and heart of the toad (Bufo marinus) was examined by use of glyoxylic acid-induced catecholamine fluorescence and peptide immunohistochemistry. All arteries possessed a moderate to dense plexus of adrenergic axons, which also showed neuropeptide Y-like immunoreactivity (NPY-LI). Some adrenergic axons in the intracardiac vagal trunks showed NPY-LI, but the varicose adrenergic axons innervating the cardiac muscle of the atria and ventricle, and the coronary blood vessels did not display NPY-LI. About half of the nerve cell bodies in the anterior sympathetic chain ganglia with dopamine-beta-hydroxylase-LI (DBH-LI) also contained NPY-LI. The nerve cell bodies with DBH-LI alone were generally larger (median diameter 30 micron) than those with both DBH-LI and NPY-LI (median diameter 20 micron). Some cell bodies showing DBH-LI alone were surrounded by boutons with NPY-LI but not DBH-LI. Axons that displayed simultaneously both substance P-LI (SP-LI) and calcitonin gene-related peptide-LI (CGRP-LI) also formed a plexus around all arteries studied, being particularly dense around the mesenteric and pulmonary arteries. These axons are most likely sensory since SP-LI was reduced by capsaicin treatment, and nerve cell bodies with both SP-LI and CGRP-LI were found in dorsal root ganglia and the vagal ganglion. A dense plexus of axons showing somatostatin-LI was located around the pulmonary artery and its main intrapulmonary branches. A few nerves with vasoactive intestinal polypeptide-LI were found around the dorsal aorta and pulmonary artery. No perivascular nerves with enkephalin-LI were observed. Reversed-phase, high-pressure liquid chromatography of acid extracts of the large arteries showed that the major peaks of NPY-LI and SP-LI co-eluted with porcine NPY (1-36) and synthetic SP (1-11), respectively. Thus, the location and structure of these peptides in perivascular nerves has been highly conserved during vertebrate evolution.

Adrenergic Fibers

Partial depletion of neuropeptide Y from noradrenergic perivascular and cardiac axons by 6-hydroxydopamine and reserpine.

The effects of 6-hydroxydopamine (6-OHDA) and reserpine on the storage of neuropeptide Y (NPY) in noradrenergic cardiovascular nerves were examined with both immunohistochemistry and radioimmunoassay (RIA). Immunohistochemical double-labelling techniques demonstrated that NPY was located only in noradrenergic axons in the guinea-pig carotid artery, mitral valve, thoracic inferior vena cava, thoracic aorta, superior mesenteric artery and small saphenous vein. Treatment with 6-OHDA in vivo eliminated noradrenergic, NPY-containing axon terminals from all tissues, but preterminal axons were still prominent in the superior mesenteric artery. The greatest depletion of NPY detected by RIA after 6-OHDA treatment was found in tissues with a predominance of terminal noradrenergic axons, such as the small saphenous vein, whereas NPY accumulating in preterminal axons masked the loss of NPY from terminal axons in the superior mesenteric artery. After treatment with doses of reserpine that led to a rapid depletion of noradrenaline (NA) from perivascular nerves, NPY was still detected histochemically at all times although levels sometimes appeared to be reduced. RIA demonstrated that the partial depletion of NPY after reserpine consisted of a rapid phase seen in the vena cava and saphenous vein after the highest doses, and a slower phase of NPY depletion from all tissues after all doses of reserpine. The greatest depletion of NPY from terminal axons by reserpine (in small saphenous vein) was 85-90%. These results demonstrate that some NPY can be stored in noradrenergic perivascular axons in the absence of noradrenaline, but that partial depletion of NPY from axon terminals results when NA stores are depleted by reserpine. The variation in extent of NPY depletion between tissues after drug treatments can be explained by variation in the ratio of preterminal to terminal axons.

Animals

The significance of longitudinal excursion in peripheral nerves.

It has been shown that nerves do, in fact, have a longitudinal excursion. This excursion is accentuated during adjacent joint motion. It is important for the surgeon treating nerve injuries, compression lesions, and adherent nerves to realize that the restoration of the longitudinal excursion of the peripheral nerves must be accomplished in order to effectively treat the inciting lesion.

Cicatrix

Co-localization of neuropeptide Y, vasoactive intestinal polypeptide and dynorphin in non-noradrenergic axons of the guinea pig uterine artery.

Two major populations of perivascular axons containing immunoreactivity to neuropeptide Y (NPY) have been revealed in the main uterine artery of the guinea pig by immunohistochemical procedures which allow the simultaneous visualization of two antigens. One population contained immunoreactivity to dopamine-beta-hydroxylase (D beta H) and was presumably noradrenergic. The other main population of axons with NPY-like immunoreactivity (NPY-LI) did not have D beta H-like immunoreactivity (D beta H-LI) and was presumably non-noradrenergic. These non-noradrenergic axons also contained immunoreactivity to vasoactive intestinal polypeptide (VIP) and dynorphin (DYN). Indeed, nearly all axons with VIP-LI also contained NPY-LI and DYN-like immunoreactivity (DYN-LI). NPY constricted the uterine artery perfused in vitro, whilst VIP dilated uterine arteries preconstricted with noradrenaline or NPY. Thus, we have evidence for the coexistence of a vasoconstrictor peptide and a vasodilator peptide in the same non-noradrenergic perivascular axons, which also contain an opioid peptide, dynorphin.

Animals

Norepinephrine-dependent and independent mechanisms of persistent effects of amphetamine in rat cerebellum.

Previous studies of the effects of chronic low-dose amphetamine (2 mg/kg per day X 21 days) on the spontaneous discharge rate of cerebellar Purkinje neurons have shown persistent depressant effects for up to 50 days after cessation of drug administration. The depression of spontaneous discharge observed was only partially reversible by various pharmacological agents which disrupt noradrenergic neurotransmission in cerebellum. In the present study, several additional approaches were used to investigate further this persistent effect. Rats were treated, either before or after chronic treatment with amphetamine, with intracisternal 6-hydroxydopamine at doses which destroy most noradrenergic fibers in cerebellum. In either case Purkinje neurons were still significantly slowed after cessation of amphetamine treatment, although the depression was not as great as previously observed. In another experiment, cerebellar cortical levels of 3-methoxy, 4-hydroxy phenyl glycol (MHPG) were measured after cessation of amphetamine administration, to determine if there was biochemical evidence for increased noradrenergic neurotransmission. At ten days, MHPG levels were elevated by 36%, and they returned to control values by 30 days. The evidence obtained in these studies suggests that chronic amphetamine treatment causes a persistent increase in noradrenergic neurotransmission, but non-noradrenergic mechanisms may also be important mechanisms in the long-lasting depression of activity of cerebellar Purkinje neurons.

Amphetamine