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Biomedical subjects

P O'Neil

Publications and source records attributed to P O'Neil.

15 recordsLinked to original sources
PubMed2004

Blood naltrexone and 6-beta-naltrexol levels following naltrexone implant: comparing two naltrexone implants.

The aim of this study was to profile and compare blood naltrexone and 6-beta-naltrexol levels with time following treatment with two sustained-release naltrexone preparations produced by GoMedical Industries, Australia at a community heroin treatment clinic in Perth, Western Australia. A sample of 10 patients who each received a 1.7 g naltrexone implant were compared to 24 patients who each received a 3.4 g naltrexone implant as treatment for heroin dependence. Blood naltrexone levels following treatment with the 1.7 g naltrexone implant remained above 2 and 1 ng/ml for approximately 90 and 136 days, respectively. Use of the 3.4 g naltrexone implant extended the period of coverage to approximately 297 (1 ng/ml) or 188 (2 ng/ml) days. Blood 6-beta-naltrexol levels remained above 10 ng/ml for approximately 18 and 83 days, respectively, following use of the 1.7 g and 3.4 g naltrexone implants. The current study data indicate that blood naltrexone and 6-beta-naltrexol levels following treatment with either the 1.7 g or 3.4 g naltrexone implant are greater than those reported in other published data on other sustained-release naltrexone preparations. Furthermore, duration of blood naltrexone and 6-beta-naltrexol levels achieved following use of the 3.4 g implant were superior to those achieved with the 1.7 g naltrexone implant, with naltrexone blood levels maintained above 2 ng/ml for a period of approximately 6.3 months compared to 3 months, respectively. The implications of this in managing the heroin-dependent patient, especially those who find it difficult to shift away from dependent use patterns, are discussed.

Adult↗
PubMed2001

Sublingual capnometry and indexes of tissue perfusion in patients with circulatory failure.

OBJECTIVE: To examine the relationship between sublingual PCO(2) (PslCO(2)) and other indexes of tissue perfusion. DESIGN: Prospective observational study. SETTING: Medical and coronary ICUs in a tertiary-care teaching hospital. SUBJECTS: Twenty-five patients with circulatory failure, 19 patients with sepsis, and 6 patients with cardiac failure. MEASUREMENTS AND MAIN RESULTS: PslCO(2), gastric intramucosal PCO(2) (PiCO(2)), arterial lactate concentration, systemic oxygen delivery, and systemic oxygen consumption were measured at baseline and at 1, 3, 6, 12, and 24 h after the beginning of the study. PslCO(2) and the PslCO(2)-PaCO(2) gradient were increased but not significantly different in nonsurvivors compared to survivors at baseline. At 24 h, the mean (+/- SE) PslCO(2) was 45 +/- 4 mm Hg in survivors and 61 +/- 4 mm Hg in nonsurvivors (p = 0.06), while the PslCO(2)-PaCO(2) gradient was 14 +/- 3 mm Hg in survivors and 29 +/- 4 mm Hg in nonsurvivors (p < 0.05). No other significant differences in survivors and nonsurvivors were observed in any other index of perfusion. For all patients, the correlations between PslCO(2) and PiCO(2) (r = 0.459; p < 0.05) and cardiac index (r = 0.285; p < 0.05) were observed. The PslCO(2)-PaCO(2) gradient also was correlated with the PiCO(2)-PaCO(2) gradient (r = 0.323; p < 0.05). When patients were placed into subsets of sepsis and cardiac failure, the strength of the correlations increased in the patients with cardiac failure (PslCO(2) vs lactate, r = 0.611 and p < 0.05; PslCO(2) vs PiCO(2), r = 0.613 and p < 0.05; PslCO(2) vs PiCO(2)-PaCO(2) gradient, r = 0.648 and p < 0.05). CONCLUSION: PslCO(2) correlated best with PiCO(2) and arterial lactate concentration in patients with cardiac failure. PslCO(2) and the PslCO(2)-PaCO(2) gradient may be useful as indexes of the severity of perfusion failure.

APACHE↗
PubMed1998

Matrix metalloproteinase-1 is associated with poor prognosis in oesophageal cancer.

The matrix metalloproteinases (MMPs) are a family of closely related proteolytic enzymes which are involved in the degradation of different components of the extracellular matrix. There is increasing evidence to indicate that individual MMPs have an important role in tumour invasion and tumour spread. Monoclonal antibodies specific for MMP-1, MMP-2, or MMP-9 have been produced, using as immunogens peptides selected from the amino acid sequences of individual MMPs. The presence of MMP-1, MMP-2, and MMP-9 in oesophageal cancer was investigated by immunohistochemistry on formalin-fixed, wax-embedded sections of oesophageal cancers. The relationship of individual MMPs to prognosis and survival was determined. MMP-1 was present in 24 per cent of oesophageal cancers, while MMP-2 and MMP-9 were present in 78 and 70 per cent of tumours, respectively. The presence of MMP-1 was associated with a particularly poor prognosis (log rank test 8.46, P < 0.004) and was an independent prognostic factor (P = 0.02). The identification of individual MMPs in oesophageal cancer provides a rational basis for use in the treatment of oesophageal cancer of MMP inhibitors which are currently undergoing clinical trial.

Adenocarcinoma↗
PubMed1997

Cycles of dose-intensive chemotherapy with peripheral stem cell support in persistent or recurrent platinum-sensitive ovarian cancer.

OBJECTIVE: The objective was to determine the toxicity and surgically documented response rate of sequential high-dose chemotherapy with peripheral stem cell support in patients with persistent or recurrent cisplatin-sensitive ovarian cancer. METHODS: Fourteen patients (average age, 45 years) were treated with cyclophosphamide (4.5 g/m2), followed by granulocyte colony-stimulating factor (G-CSF)-stimulated peripheral stem cell harvests. The subsequent regimen prescribed three courses of carboplatin (1 g/m2) and cyclophosphamide (1.5 g/m2 with 2-mercaptoethanesulfonate) every 2 weeks with stem cell support. This was followed by three courses of paclitaxel at 250 mg/m2 every 2 weeks with G-CSF support only. Six patients were entered on the basis of a positive second-look laparotomy and 8 patients had a first recurrence after at least a 6-month disease-free interval. RESULTS: Fourteen patients were entered and 12 patients completed all planned courses of therapy (mean time, 13 weeks). Normal hematopoiesis was reestablished after each cycle. Hospitalization for neutropenic fever occurred in 11/93 cycles (11.8%). Thirteen patients required blood transfusions and in 12 patients platelet transfusions were given. One patient had grade 3 neurotoxicity. An initial elevated CA 125 returned to normal in 7/8 patients (88%) and 71% of patients with measurable disease responded to therapy. There were 2 pathologic complete responders (PCR), making the PCR rate 2/14 or 14% (0-35%). CONCLUSION: Although this regimen was well tolerated and clinical response rates were high, the surgically documented response rate was not clearly superior to conventional salvage regimens in platinum-sensitive patients.

Adult↗
PubMed1996

Matrix metalloproteinase-1 is associated with poor prognosis in colorectal cancer.

Colorectal cancer is one of the commonest malignant tumors and has a relatively poor prognosis. The outcome depends on the extent of local and particularly metastatic tumor spread. The matrix metalloproteinases (MMPs) are a family of closely related enzymes that degrade the extracellular matrix and are considered to be important in facilitating tumor invasion and spread (1-3). Using immunohistochemistry we have investigated the occurrence in colorectal cancer of MMP-1 (interstitial collagenase). Our monoclonal antibody was prepared against a synthetic peptide corresponding to an amino acid sequence specific for MMP-1 and was selected to react in formalin-fixed wax-embedded sections, thus allowing use in diagnostic histopathology and also enabling access to archival material. We found that the presence of MMP-1 in colorectal cancer is associated with a poor prognosis (P = 0.006) and has prognostic value independent of Dukes stage. One MMP inhibitor that strongly inhibits MMP-1 has already been shown to inhibit growth of human colon cancer xenografts in nude mice (4). Our results suggest that treatment of those individuals whose colon tumors produce MMP-1 with MMP inhibitors is a therapeutic strategy worth pursuing.

Animals↗
PubMed1996

Intraventricular neurocytoma.

Intraventricular neurocytoma is a rare cerebral tumour which is usually associated with a good prognosis. It has imaging features which help differentiate it from other cerebral tumours. We report three cases including the first to originate from the pineal gland. The report emphasizes the radiological appearance and reviews the literature.

Adolescent↗
PubMed1996

The severity of alpha-particle-induced DNA damage is revealed by exposure to cell-free extracts.

The rejoining of single-strand breaks induced by alpha-particle and gamma irradiation in plasmid DNA under two scavenging conditions has been compared. At the two scavenger capacities used of 1.5 x 10(7) and 3 x 10(6) s-1 using Tris-HCl as the scavenger, the ratio of single- to double-strand breaks for alpha particles is fivefold less than the corresponding ratios for gamma irradiation. The repair of such radiation-induced single-strand breaks has been examined using a cell-free system derived from human whole-cell extracts. We show that the rejoining of single-strand breaks for both alpha-particle- and gamma-irradiated plasmid is dependent upon the scavenging capacity and that the efficiency of rejoining of alpha-particle-induced single-strand breaks is significantly less than that observed for gamma-ray-induced breaks. In addition, for DNA that had been irradiated under conditions that mimic the cellular environment with respect to the radical scavenging capacity, 50% of alpha-particle-induced single-strand breaks are converted to double-strand breaks, in contrast with only approximately 12% conversion of gamma-ray-induced single-strand breaks, indicating that the initial damage caused by alpha particles is more severe. These studies provide experimental evidence for increased clustering of damage which may have important implications for the induction of cancer by low-level alpha-particle sources such as domestic radon.

Alpha Particles↗
PubMed1991

Cystic cerebellar schwannoma: case report.

We report a case of cerebellar schwannoma in a 64-year-old woman. The tumor was defined on computed tomographic and magnetic resonance imaging scans and confirmed on surgery. The solid part of the tumor appeared to be derived from the inferior vermis of the cerebellum, the cystic part extending toward the medulla oblongata and the foramen magnum. The problem of preoperative diagnosis based on magnetic resonance imaging findings is discussed.

Cerebellar Neoplasms↗
PubMed1990

CSF monoamine levels in normal-weight bulimia: evidence for abnormal noradrenergic activity.

Normal-weight bulimic patients have disturbed appetite, mood, and neuroendocrine function and often respond to antidepressants. Since these findings suggest abnormalities in brain monoaminergic pathways, the authors measured CSF monoamine concentrations in 27 normal-weight bulimic patients and 14 volunteers. Bulimic patients had a significantly lower mean CSF norepinephrine concentration. Levels of CSF 5-HIAA, the major serotonin metabolite, and CSF HVA, the major dopamine metabolite, were normal, although more frequent binge-eating in bulimic subjects was associated with a significantly lower CSF HVA level. Whether trait- or state-related, monoaminergic disturbances are part of this disorder's neurobiological syndrome. The lower CSF norepinephrine concentration suggests bulimia is not simply a variant of affective disorders.

Adult↗
PubMed1987

Recent studies on selective serotonergic antidepressants: trazodone, fluoxetine, and fluvoxamine.

In recent years, the role of serotonin in the pathophysiology of depressive disorders has been intensively studied. These studies have been complemented by the development of newer antidepressant agents that exert specific effects on serotonin systems. This paper reviews the pharmacology of these newer compounds and contrasts it with those of the standard tricyclic antidepressants. The current status of various serotonergic agents is discussed. Results are reviewed from recent double-blind studies comparing three compounds (trazodone, fluoxetine, and fluvoxamine) to a standard tricyclic antidepressant. Relative efficacy, dropout rates, optimal dosages, and side effects are emphasized. Data from studies on trazodone and fluoxetine suggest that lower dosages may prove as effective (if not more effective) than very high dosages. Implications of these data are discussed. Side effects of fluoxetine and fluvoxamine include primarily nausea, weight loss, insomnia, and anxiety. Possible application of specific serotonin reuptake blockers in the treatment of obsessive-compulsive disorder and in the reduction of alcohol consumption is also reviewed.

Animals↗