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Biomedical subjects

T P O'Neill

Publications and source records attributed to T P O'Neill.

At least 19 recordsLinked to original sources
PubMed2000

Determination of norepinephrine in small volume plasma samples by stable-isotope dilution gas chromatography-tandem mass spectrometry with negative ion chemical ionization.

A stable-isotope based gas chromatography-tandem mass spectrometry-negative ion chemical ionization method was developed for the determination of norepinephrine (NE) levels in small volumes (25-100 microl) of plasma. NE was stabilized in plasma by the addition of semicarbazide and spiked with deuterium-labeled norepinephrine internal standard. The analytes were isolated from the plasma by solid-phase extraction using phenylboronic acid columns and derivatized using pentafluoropropionic anhydride. The derivatized analytes were chromatographed on a capillary column and detected by tandem mass spectrometry with negative ion chemical ionization. Unparalleled sensitivity and selectivity were obtained using this detection scheme, allowing the unambiguous analysis of trace levels of NE in small-volume plasma samples. Linear standard curves were obtained for NE over a mass range from 1 to 200 pg per sample. The method had a limit of quantitation of 10 pg NE/ml plasma when using a 100-microl sample aliquot (1 pg/sample). Accuracy for the analysis of plasma samples spiked with 10 to 200 pg NE/ml typically ranged from 100+/-10%, with RSD values of less than 10%. The methodology was applied to determine the effect of clonidine on plasma NE levels in conscious spontaneously hypertensive rats. Administration of clonidine (30 microg/kg) produced an approximately 80% reduction in plasma NE accompanied by a 30% reduction in heart and mean arterial pressure that persisted >90 min after drug administration. The ability to take multiple samples from individual rats allowed the time course for the effect of clonidine to be mapped out using only one group of animals.

Animals↗
PubMed1999

Ultrasound-guided needle biopsy of the breast.

BACKGROUND: To determine the role of office-based ultrasound in the early clinical evaluation of breast masses, a consecutive series of diagnostic and interventional breast ultrasounds performed in the surgeon's office were prospectively studied. METHODS: A series of 1028 diagnostic ultrasounds were performed in 662 patients over 2 years. The clinical-pathologic data from those patients undergoing ultrasound-guided fine-needle aspiration biopsy (FNAB; n = 267 patients) and/or core needle biopsy (CNB; n = 210 patients) were reviewed. RESULTS: Of the 267 patients undergoing initial FNAB, 179 cysts were identified; 25 patients underwent no additional intervention, and 63 patients with apparently solid lesions underwent subsequent CNB. Core needle biopsy was the initial interventional approach in 147 cases. Of the 210 total patients in whom a CNB was performed, needle biopsy pathologic findings included:fibroadenoma, 57 patients; fibrocystic breast change, 82 patients; carcinoma, 53 patients; abscess/cyst, 12 patients; and other, 6 patients. Operative excision was performed in 106 of these 210 patients. There was a significantly higher false-negative rate among those patients who underwent an initial FNAB (20%; 2/10 patients) as compared with those patients undergoing CNB (3.6%; 2/55 patients; P < . 05). No cancers have been identified in those patients undergoing a benign CNB and followed for 6 to 30 months (median, 18 months). CONCLUSION: Office-based diagnostic ultrasound and interventional ultrasound that uses core needle biopsy is an effective adjunct to the early clinical evaluation of breast masses.

Adipose Tissue↗
PubMed1998

Rapid and selective method for norepinephrine in rat urine using reversed-phase ion-pair high-performance liquid chromatography-tandem mass spectrometry.

A rugged, high-throughput HPLC-MS-MS-based method, suitable for quantitation of norepinephrine (NE) in urine, has been developed. A rapid, batch-mode procedure utilizes alumina to isolate NE and its deuterated internal standard from urine. After release of NE, using dilute formic acid, samples are analyzed by isocratic reversed-phase ion-pair HPLC, with electrospray ionization (ESI) and MS-MS detection. The ion-pair reagent, heptafluorobutyric acid, is compatible with the ESI interface and permits use of mobile phases with relatively high methanol content, enhancing ESI sensitivity. Furthermore, no significant drop in sensitivity is observed throughout more than 15 h of instrument operation. The selectivity of this approach permitted simplification of the extraction procedure and reduced run times (under 4 min), making single batch-run sizes of more than 200 samples practical. The lower limit of quantitation is 5 ng per 0.5 ml sample, with analytical recoveries of 97-100% and overall method precision of better than 4% relative standard deviation verified up to 500 ng ml(-1). This method was initially applied to study the diurnal rhythm in sympathetic nervous system activity of spontaneously hypertensive rats.

Animals↗
PubMed1998

Breast ultrasound.

Ultrasound of the breast has been demonstrated to be an extremely effective tool in the evaluation of mammographically detected breast lesions. The technique is relatively straightforward and may be learned in a relatively short time by experienced breast clinicians. It is likely that the future care of patients with diseases of the breast will continue to be increasingly dependent on image-guided breast biopsy techniques. Therefore, surgeons would do well to familiarize themselves with this modality. This is likely to streamline patient care, improve cost efficiency, and facilitate therapeutic planning. Finally, the current health care climate is likely to encourage the use of ultrasound of the breast by surgeons.

Biopsy, Needle↗
PubMed1994

Effect of acoustic streaming on ultrasonic heating.

It was found in in vitro experiments performed on tissue phantoms that acoustic streaming in low attenuating fluid may dramatically reduce the temperature rise generated by ultrasound at the surface of bone, if the ultrasound path contains a low-attenuating-fluid/thin-soft-tissue/bone structure. The temperature rise at the surface of bone generated by a 3.5 MHz focused ultrasound beam of 180 mW source acoustic power and an average acoustic intensity at the focus of 5.8 W/cm2 was measured to be only 18% of the value predicted by an existing model, when the bone was in contact with the low attenuating fluid. When a bone surface that is covered by 1 mm thick soft tissue is exposed to the same ultrasound beam, the measured temperature rise at the tissue-bone surface is only 60% of the calculated value.

Acoustics↗
PubMed1994

Ultrasound heating in a tissue-bone phantom.

Temperature rise generated by focused ultrasound beams was tested on semipermanent tissue-bone phantoms. The phantoms were capped (sealed) plastic hollow cylindrical containers filled with tissue-mimicking material (TMM), in which were imbedded 25 microns diameter copper-constantan thermocouples (TC) and a piece of compact human or cow bone. The acoustic frequency specific attenuation coefficient of TMM was adjusted to be 0.3 dB cm-1 MHz-1 as specified by the FDA for a frequency range of 1-5 MHz. A high density 0.318 cm thick polyethylene sheet was chosen as the material to make caps of the phantoms. A formula developed to estimate the upper limit of temperature rises at tissue-bone interfaces generated by focused ultrasound has been proved to be appropriate experimentally using the semipermanent phantoms.

Animals↗
PubMed1993

The toxicologic and oncogenic potential of JP-4 jet fuel vapors in rats and mice: 12-month intermittent inhalation exposures.

Three-hundred Fischer 344 rats and 300 C57BL/6 mice of each sex were divided into three treatment groups and exposed intermittently (6 hr/day, 5 days/week) to JP-4 jet fuel vapors at concentrations of 0, 1000, and 5000 mg/m3 for 12 months. At exposure termination, 10% of the animals were killed and those remaining were held for a 12-month postexposure tumorigenesis observation period. Pathologic findings in male rats revealed treatment-related renal toxicity and neoplasia consistent with the male rat unique alpha 2 mu-globulin nephropathy syndrome. Distinct JP-4-induced respiratory toxicity was not observed, and pulmonary neoplasms were not significantly increased in any treatment group. Benign hepatocellular adenomas were slightly increased in high-dose female mice, but the trend was reversed in male mice. Other pathologic findings were regarded as equivocal or compatible with expected biologic variation. The study did not demonstrate target organ toxicity or carcinogenesis which could be extrapolated to other species.

Administration, Inhalation↗
PubMed1993

Registry of Experimental Cancers of the National Cancer Institute. A database resource for cancer research.

The National Cancer Institute established the Registry of Experimental Cancers in March 1970. This registry consists of a permanent collection of pathological materials on spontaneous and induced lesions in laboratory animals that includes histological slides, paraffin blocks, autopsy findings, pathological diagnoses, photographs, and experimental records. The material presently is composed of approximately 60,000 consecutive records and is a valuable resource for researchers interested in tumors and other lesions arising spontaneously or from specific induction protocols in experimental animals. The entire registry database was transferred to an object-oriented database that permits registry staff to write programs for the different data field objects, thus customizing searches and other database functions. Twenty-seven animal species are represented and a total of 6,496 diagnostic entities and 1,106 treatment and control protocols are listed. Archival material may be retrieved for analysis of molecular markers.

Animals↗
PubMed1991

Lymphocyte transformation abnormalities in bovine immunodeficiency-like virus infected calves.

Bovine immunodeficiency-like virus (BIV) is a lentiviral pathogen of cattle which is genetically and antigenically related to the human immunodeficiency virus (HIV-1). To determine the impact of BIV infection on the bovine immune system we studied the lymphocyte transformation responses of male Holstein calves inoculated with BIV strain R-29 to three mitogens: pokeweed mitogen (PWM), concanavalin A (Con A), and phytohemagglutinin (PHA) at two and six months post-infection. By six months post-inoculation the response to all three mitogens was diminished compared to control animals and remained depressed 10 months post-inoculation. These results demonstrate that a functional impairment of lymphocytes can be observed early in the course of BIV infection, and prior to the onset of overt clinical disease.

Animals↗
PubMed1991

Mechanism of capsaicin action: recent learnings.

Capsaicin has long been known to act selectively on a subpopulation of neurons to produce initial excitation, followed by a prolonged neuroinhibitory action commonly referred to as 'capsaicin desensitization'. This property has been exploited extensively as a tool with which to investigate the role of these nerves in the normal and pathophysiology of the airways. However, the cellular basis for these effects is only now beginning to be understood. The purpose of this review is to summarize recent findings that provide new insights into the mechanisms by which capsaicin acts to exert its effects. These findings suggest that capsaicin acts at a receptor that is either tightly coupled to, or indeed is, a relatively non-selective cation channel. Binding of capsaicin to this receptor allows both sodium and calcium (and possibly potassium) ions to flow down their concentration gradients, causing initial depolarization and neurotransmitter release. Prolonged exposure to capsaicin produces a subsequent desensitization or neuroinhibition. The neuroinhibition has now been shown to be of two types: capsaicin-specific and non-specific. The former is characterized by a loss of the acute excitatory response evoked by application of capsaicin, but maintained responses to other stimuli. The latter is characterized by a loss of responsiveness to all stimuli and is probably associated with the neurotoxic effect of this agent. Despite these recent findings, many questions remain regarding the nature and physiological role of the capsaicin receptor. The availability of two new probes for this receptor, ruthenium red and resiniferatoxin, promises to provide at least some of the answers to these intriguing questions.

Action Potentials↗
PubMed1989

Synthetic capsaicin reversibly impairs vasopressin-mediated blood pressure recovery.

The vasopressin-mediated recovery of arterial pressure observed in adult rats following pharmacological blockade of the sympathetic nervous and renin-angiotensin systems is reduced by neonatal capsaicin treatment. We now demonstrate a similar but reversible effect following treatment of adult Wistar or Sprague-Dawley rats with N-vanillylnonanamide (50 mg/kg sc). One day after treatment, Wistar, but typically not Sprague-Dawley, rats had lost weight and exhibited increased sensitivity to the anesthetic effects of methohexital sodium. In both strains, captopril treatment caused hypotension. After captopril and ganglionic blockade, vasopressin-mediated recovery of arterial pressure was significantly inhibited. Furthermore, treated Wistar rats had reduced sensitivity to the ocular irritancy of N-vanillylnonanamide when examined 2 days postdose. All deficits reversed within 2 wk of dosing. These data suggest that capsaicin-sensitive systems participate in homeostatic mechanisms engaged during acute hypotension. Because the dose of N-vanillylnonanamide employed in the present study has previously been shown to destroy unmyelinated afferent fibers when administered to adult rats, recovery of the functional deficits may reflect regeneration of damaged processes or assumption of their function by undamaged neurons innervating adjacent sites. By extrapolation from other studies of capsaicin, damage to some central neurons may also be involved.

Animals↗
PubMed1989

Hepatocellular foci--a regulator's Gordian.

Recently, the Food and Drug Administration has received several petitions which raise the question of the significance of an increased number of treated rats with foci of hepatocellular alteration. Study pathologists are responsible for defining the diagnostic criteria used in any study to diagnose proliferative changes in the liver. Similarly, study pathologists, based on their observations of the overall liver findings, are responsible for assessing the biological significance of any lesion observed and including their appraisal in the written pathology narrative which should accompany any petition sent to a regulatory agency. Current scientific knowledge regarding the incidence of animals with foci of cellular alteration suggests that the historical control incidence of animals with this change is somewhat less than is currently being observed. While some foci of cellular alteration may progress to neoplastic lesions, it is not possible to unequivocally predict whether carcinogenic activity may be demonstrated, based only on the incidence of animals with foci of cellular alteration. The Food and Drug Administration, for the foreseeable future, will continue to examine the incidence of animals with selected proliferative liver lesions, including foci of cellular alteration, on a case by case basis.

Animals↗
PubMed1987

Role for the median preoptic nucleus in centrally evoked pressor responses.

Recent evidence suggests an important role for the median preoptic nucleus (MnPO) in cardiovascular responses evoked by angiotension II (ANG II). We therefore planned to determine whether selective inactivation of this nucleus would produce deficits in pressor responsiveness to centrally administered ANG II and carbachol. Chronic disruption of MnPO by electrolytic lesion produced pressor deficits to centrally administered ANG II and carbachol but did not change resting arterial pressure. In addition, blockade of neuronal activity in MnPO produced by the microinjection of the local anesthetic lidocaine reversibly attenuated pressor responses to these agents without producing any change in resting arterial pressure. The microinjection of ANG II itself into sites in which lidocaine blocked ANG II pressor responses had no effect on arterial pressure but did produce drinking. These data suggest that the MnPO, although not acting as a receptor site for the pressor effect of ANG II, plays an important role in mediating the pressor response evoked by centrally administered ANG II and carbachol.

Angiotensin II↗
PubMed1986

Activation of vagal depressor reflexes by atriopeptins inhibits renal sympathetic nerve activity.

Atrial natriuretic factor decreases arterial pressure but the hypotensive response is not accompanied by the expected reflex tachycardia. The absence of reflex tachycardia might reflect a stimulating effect of atrial natriuretic factor [atriopeptins (AP)] on cardiac-sensory receptors with vagal afferents. To test the hypothesis that AP inhibit sympathetic nerve activity by activating vagal afferents we measured changes in renal sympathetic nerve activity (SNA), heart rate, and arterial pressure during injection of APII and APIII in anesthetized Sprague-Dawley rats in the intact state, after sinoaortic denervation, and after sinoaortic denervation plus bilateral vagotomy. In intact, anesthetized rats APIII (50 micrograms/kg) lowered mean arterial pressure [-31 +/- 8 (SE) mmHg] without the expected reflex increase in renal SNA and heart rate. In contrast, infusion of sodium nitroprusside in a dose that produced a similar decrease in mean arterial pressure (-29 +/- 9 mmHg) evoked a significant increase in renal SNA (+38 +/- 8%) and heart rate (+17 +/- 5 beats/min). In rats with sinoaortic denervation, APIII induced a greater fall in mean arterial pressure (-44 +/- 8 mmHg). This hypotensive response was associated with a decrease in renal SNA (-26 +/- 2%) that was abolished by bilateral vagotomy. Atropine did not attenuate the decrease in renal SNA with APIII. We conclude that APII and APIII increase the activity of vagal afferents and thereby inhibit the increases in renal SNA and heart rate, which would be expected to result from the fall in arterial pressure. We speculate that this action might facilitate reflexly the renal vasodilator and natriuretic actions of APs.

Animals↗
PubMed1985

Effects of clonidine on neuronal firing evoked by a noxious stimulus.

When norepinephrine was applied microiontophoretically to certain neurons in the pontine reticular formation of rats, it produced an increase in neuronal firing like that produced by noxious stimulation. Previous studies have shown that both noxious stimulus- and norepinephrine-evoked increases in neuronal firing are mediated by alpha-adrenoceptors. These neurons were unresponsive to non-noxious stimuli, suggesting that they might play a role in nociception. Microiontophoretic or systemic administration of the selective alpha 2-adrenoceptor agonist clonidine significantly attenuated noxious stimulus-evoked firing, but had little effect on firing evoked by norepinephrine. This effect of clonidine could be prevented by the alpha 2-adrenoceptor antagonists piperoxan and yohimbine. These antagonists, when given alone, increased noxious stimulus-evoked firing, but had no effect on firing evoked by norepinephrine. In contrast, the selective alpha 1-adrenoceptor antagonist ARC-239 (2-(2,4-(o-methoxyphenyl)-piperazin-1-yl)ethyl-4,4-dimethyl-1,3-(2 H,4) isoquinolindione dihydrochloride) attenuated both noxious stimulus- and norepinephrine-evoked firing. These data are consistent with the hypothesis that presynaptic alpha 2-adrenoceptors modulate the release of norepinephrine. Furthermore, these data suggest that the pontine reticular formation is one site at which clonidine could act to produce analgesia.

Animals↗
PubMed1985

An outbreak of cerebrocortical necrosis (polioencephalomalacia) in goats.

In a herd of 30 Boer goats, 3 young goats developed nervous signs including apparent blindness. In 2 of the goats a diagnosis of cerebrocortical necrosis was confirmed by the demonstration of lesions typical of the disease on histopathological examination. Lead concentrations in the renal cortex were well below the level regarded as indicative of lead poisoning in ruminants. The reason for the outbreak was not clear, but the feeding of concentrate and poor quality roughage may have been contributory factors. Cerebrocortical necrosis appears to be unusual in goats, compared to cattle and sheep, but it should be entertained in the differential diagnosis of caprine nervous diseases.

Animals↗
PubMed1983

Interactions of morphine with putative neurotransmitters in the mesencephalic reticular formation.

Acetylcholine (ACh) and norepinephrine (NE) have been identified previously as putative nociceptive neurotransmitters in the mesencephalic reticular formation (MRF) of the rat because they frequently mimic the change in neuronal firing (usually an increase) evoked by a noxious stimulus (NS). The purpose of this study was to determine if 1.) morphine (M) acts to prevent the increase in firing evoked by a NS by blocking the effects of either of these two neurotransmitters and 2.) if this effect is a specific narcotic effect. Using the technique of microiontophoresis in conjunction with extracellular recording, we located single units in the MRF in which 1.) neuronal firing was accelerated by a NS: 2.) M blocked this response; and 3.) either ACh or NE mimicked the effect of the NS. Neurons meeting these three criteria were studied further to determine if morphine would also block the response to either of the neurotransmitters and if this was a specific narcotic effect. We found that morphine blocked the increase in neuronal firing evoked by the NS and ACh or the NS and NE in over 50% of the cells meeting the above criteria. Some neurons were found in which both ACh and NE mimicked the NS and M blocked all three responses. This blockade of these neurotransmitters was a specific narcotic effect because it could be reversed by the systemic administration of naloxone. These data lead to the tentative hypothesis that M, acting via an opiate receptor, blocks the increase in neuronal firing evoked by a NS by blocking the postsynaptic effects of either ACh or NE. This may be one of the mechanisms by which morphine acts to produce analgesia.

Acetylcholine↗