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Biomedical subjects

J Hanlon

Publications and source records attributed to J Hanlon.

At least 19 recordsLinked to original sources
PubMed2002

Metallothionein in bovine spongiform encephalopathy.

An increase in metallothionein I and II (MT I/II) mRNA concentrations has been reported in the central nervous system of scrapie-infected rodents. In this study we compared cattle with bovine spongiform encephalopathy (BSE), cattle affected by neurological disease other than BSE, and clinically healthy cattle in respect of MT I/II immunoreactivity in brainstem medullary tissue. Marked astrocytic MT I/II immunolabelling was seen in all BSE-affected animals, in contrast to clinically healthy cases, in which no such labelling was detected. In BSE, MT I/II immunoreactive astrocytes were confined specifically to areas of vacuolation or abnormal prion protein (PrP(BSE)) deposition, or both. MT I/II immunolabelling was also seen in a small number of animals with a neurological disease other than BSE. These findings complement previous studies by demonstrating increased levels of MT I/II in transmissible spongiform encephalopathy (TSE)-infected brain tissue, indicating that MT I/II may play some as yet unidentified role in the response to TSE infection.

Animals↗
PubMed1999

A comparison of transnasal and transoral endoscopy with small-diameter endoscopes in unsedated patients.

BACKGROUND: The aim of this study was to compare use and tolerance of transnasal and transoral diagnostic endoscopy with small-diameter endoscopes in unsedated patients. METHODS: Patients being seen for diagnostic endoscopy were randomly assigned to have an unsedated transnasal or transoral procedure. Two prototype narrow-diameter endoscopes (a 5.3 mm fiberoptic endoscope and a 5.9 mm videoendoscope) were used. RESULTS: Of 170 patients (64 women and 106 men) enrolled, 86 underwent transoral and 84 underwent transnasal endoscopy. The procedure was successfully completed using the transoral route in 85 of 86 patients and using the transnasal route in 74 of 84 patients (p = 0.004). Sixteen patients experienced mild epistaxis after transnasal endoscopy. The larger videoendoscope, when compared with the fiberoptic endoscope, accounted for a significantly higher proportion of failures (8 of 41 vs. 2 of 43, p = 0.046) and cases of epistaxis (12 of 33 vs. 4 of 41, p = 0.007). The time taken for transoral endoscopy was shorter than the transnasal route (oral mean 13.7 +/- 0.5 minutes, nasal mean 15.2 +/- 0.6 minutes, p = 0.054). There was no difference between the 2 groups with respect to tolerance of the procedure. From the endoscopist's perspective, the only statistically significant difference between the 2 groups was that endoscope insertion was easier by the oral route (p = 0.007). CONCLUSIONS: Unsedated transnasal endoscopy with the videoendoscope was less successful compared with the transnasal fiberoptic instrument or when compared with either instrument passed transorally. Use of the larger diameter videoendoscope also resulted in significantly more epistaxis in the transnasal endoscopy group. Endoscopists find transoral introduction of the endoscope easier; this may reflect their relative unfamiliarity with the nasal route. Once intubation has been successfully achieved for either route, patient tolerance is the same.

Adult↗
PubMed1998

Analysis of the value of empiric vancomycin administration in febrile neutropenia occurring after autologous peripheral blood stem cell transplants.

We conducted a retrospective review of 125 patients undergoing high-dose therapy and stem cell rescue in order to evaluate the incidence of documented infection and the utility of the administration of vancomycin empirically. All patients received prophylactic oral quinolone therapy. Because neutropenia in this setting is relatively brief, 21 patients never manifested fever, and no patient died of infection. Of the remaining 104 patients, positive blood cultures were obtained in only 10, nine with a gram stain positive and one with a gram stain negative organism. Sixty-two patients without any evidence of gram positive infection received vancomycin according to the existing algorithm for care of neutropenic fevers. In this population of patients, empiric administration of vancomycin for neutropenic fevers without culture documentation appears to be unnecessary, could be discontinued safely and at substantial cost savings, and might slow the appearance of vancomycin-resistant organisms.

Adult↗
PubMed1997

Evaluation of PCR and ELISA assays for screening clinical trial subjects for replication-competent retrovirus.

Gene delivery via murine-based recombinant retroviral vectors is currently widely used in gene therapy clinical trials. The vectors are engineered to be replication defective by replacing the structural and nonstructural genes of a cloned infectious retrovirus with a therapeutic gene of interest. The retroviral particles are currently generated in packaging cell lines, which supply all retroviral proteins in trans. Recombination between short homologous regions of the retroviral vector and packaging cell line elements can theoretically generate replication-competent retrovirus (RCR) and hence the Food and Drug Administration (FDA) requires the monitoring of clinical trial subjects for the presence of RCR. Sensitive polymerase chain reaction (PCR) assays have been used for the detection of murine leukemia virus (MLV) nucleotide sequences in peripheral blood mononuclear cells (PBMCs). A novel serological enzyme-linked immunosorbent assay (ELISA) for the detection of anti-MLV specific immunoglobulin (Ig) has been developed to be used as an alternative to the PCR assay. Both assays were used to monitor human immunodeficiency virus (HIV)-positive clinical trial subjects who had received multiple injections of HIV-IT (V), a retroviral vector encoding HIV-1 IIIBenv/rev. Western blot analysis and an in vitro vector neutralization assay were used to characterize further a subset of serum samples tested by ELISA. Results show no evidence of RCR infection in clinical trial subjects. PCR and ELISA assays are discussed in terms of their advantages and limitations as routine screening assays for RCR. The PCR assay is our current choice for monitoring clinical trial subjects receiving direct administration of vector, and the ELISA is our choice for those receiving ex vivo treatment regimens.

Antibodies, Viral↗
PubMed1991

Phase I trial of piritrexim capsules using prolonged, low-dose oral administration for the treatment of advanced malignancies.

A phase I trial of piritrexim was conducted by use of a prolonged, low-dose oral schedule. A number of different regimens were tested, including daily dosing for 21 days followed by 7 days of no drug therapy; continuous dosing; and daily dosing for 5 of 7 days for 3 consecutive weeks followed by a week of rest. Dose escalation was accomplished by increasing the dosing frequency from once a day to twice a day and then to three times a day and by increasing the number of days of administration. Fifty-one patients with advanced cancer were entered in the study. One hundred twenty-four (96%) of 129 courses were considered assessable. Myelosuppression proved to be the dose-limiting toxic effect. Other toxic effects included stomatitis, nausea and vomiting, anorexia, diarrhea, skin rash, fatigue, and elevation of liver transaminase levels. Antitumor activity was observed in patients with melanoma and bladder cancer, and disease stabilization occurred in those with sarcoma and pheochromocytoma. The recommended dosing schedule for phase II clinical trials is 25 mg three times a day for 5 days for 3 consecutive weeks followed by 1 week of no drug therapy.

Administration, Oral↗
PubMed1991

Phase II trial of piritrexim in metastatic melanoma using intermittent, low-dose administration.

A phase II trial of piritrexim (2,4-diamino-6[2,5-dimethoxybenzyl]-5-methyl pyrido-[2,3d] pyrimidine, 301U74; PTX) was conducted for patients with metastatic malignant melanoma using an intermittent, low-dose oral administration schedule. PTX was administered at a starting dose of 25 mg orally three times per day for 5 days weekly for 3 weeks followed by 1 week of rest. Thirty-one patients were entered onto the study. Among 31 patients assessable for response, there were two complete responses (CRs) and five partial responses (PRs) for a response rate (CR plus PR) of 23% (95% confidence limit, 10% to 42%). Five responses occurred in soft tissue lesions, and two responses occurred in lung lesions. The initial dose schedule was well tolerated. The dose-limiting toxicity was myelosuppression. PTX administered in this schedule appears to be active against malignant melanoma. Further clinical trials to confirm these results are underway.

Administration, Oral↗
PubMed1990

Why do polyethylene crystals have sectors?

High-resolution (3.7 A in optical diffraction) electron microscope images have been obtained from a series of n-paraffin monolamellar crystals with chain lengths from n-C36H74 to n-C82H166. The higher molecular weight specimens, which do not undergo chain folding, form sectorized crystals and the molecular packing is found to include alternate bands of untilted and tilted chains along <130>. Their widths are consistent with those of Bragg fringe widths in bright-field images obtained at lower magnification. The chain tilt axis is near d*110. Lower molecular weight paraffins form nonsectorized crystals where the chains are generally untilted with occasional small inclinations around nonspecific axes. Surface decoration of the longer alkanes with polyethylene crystallites, first of all, reveals three preferred polyethylene crystal rod orientations ([100] plus two perpendicular to [110]) instead of the two commonly found for the lower alkane. Control studies on solid-solution crystals reveal that the third [100] orientation is a result of slight surface roughness due to unequal chain lengths or surface protrusions of chains; the new decoration is also randomly distributed. For pure n-C60H122 lamellae, however, suggestions of regular bands containing rods along [100], due to surface discontinuities along <130>, can also be seen. In contrast with polyethylene, these data suggest that crystal sectorization may be a function of chain-stem packing alone and that chain folds may play merely a secondary role in the polymer--e.g., by directing the collapse of pyramidal crystals on a flat surface.

Journal Article↗