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Biomedical subjects

B Flanagan

Publications and source records attributed to B Flanagan.

At least 19 recordsLinked to original sources
PubMed2001

Discrimination of 1990s original automotive paint systems: a collaborative study of black nonmetallic base coat/clear coat finishes using infrared spectroscopy.

The 1990s saw the introduction of significantly new types of paint binder chemistries into the automotive finish coat market. Considering the pronounced changes in the binders that can now be found in automotive paints and their potential use in a wide variety of finishes worldwide, the Paint Subgroup of the Scientific Working Group for Materials (SWGMAT) initiated a validation study to investigate the ability of commonly accepted methods of forensic paint examination to differentiate between these newer types of paints. Nine automotive paint systems typical of original equipment applications were acquired from General Motors Corporation in 1992. They consisted of steel panels coated with typical electrocoat primers and/or primer surfacers followed by a black nonmetallic base coat and clear coat. The primary purpose of this study was to evaluate the discrimination power of common forensic techniques when applied to the newer generation original automotive finishes. The second purpose was to evaluate interlaboratory reproducibility of automotive paint spectra collected on a variety of Fourier transform infrared (FT-IR) spectrometers and accessories normally used for forensic paint examinations. The results demonstrate that infrared spectroscopy is an effective tool for discriminating between the major automotive paint manufacturers' formulation types which are currently used in original finishes. Furthermore, and equally important, the results illustrate that the mid-infrared spectra of these finishes are generally quite reproducible even when comparing data from different laboratories, commercial FT-IR instruments, and accessories in a "real world," mostly uncontrolled, environment.

Journal Article↗
PubMed2000

Discography.

Discography is a diagnostic tool that has been used for many years. Although controversial, it provides a physiologic test for evaluation of a disc with a volumetric, manometric, radiographic, and pain-provocative challenge. Although it has a controversial past, when the anatomy and pathophysiology are considered particularly in relation to intradiscal pressure and applied loads (that correlate with daily activities of the patient), the interpretation of the results of discography become more objective and reproducible. As with any procedure, indications for patient selection are an important step in successful outcomes. The equipment and technique used for performing discography using a manometry system are described in this article, as are a review of complications and outcomes. Discography is a safe, accurate, reproducible, objective diagnostic tool when tested for volume, pressure, fluoroscopic changes, and pain provocation.

Fluoroscopy↗
PubMed2000

Anaesthetic simulators: training for the broader health-care profession.

BACKGROUND: The use of high-fidelity patient simulators for training health-care professionals has increased rapidly in recent years. Approximately 150 simulation training centres operate internationally. Australasia has acquired four centres since 1997. A large component of simulator-based training is experiential. METHODS: Participants manage clinical scenarios on lifelike computer-controlled mannikins within realistic clinical environments. Afterwards they actively reflect upon the experience, an exercise that is facilitated by observation of a video replay of the event. RESULTS: This approach to training promotes a consideration of broader issues which can influence clinical practice and patient outcomes. This has particular relevance to emergencies. Here, events that are by nature infrequent and unscheduled can be addressed in a controlled fashion, in an environment that is supportive and separated from actual patients. CONCLUSIONS: A broad range of skills can be addressed with this resource. Of key importance are situational management and team effectiveness skills. Deficiencies with respect to these 'non-clinical' skills are being increasingly identified for their contribution to preventable adverse events within the health-care environment. Multidisciplinary operation-room team training has the potential to address these issues as they relate to the perioperative environment.

Anesthesiology↗
PubMed1999

Phenotypic consequences of rearranging the P, M, and G genes of vesicular stomatitis virus.

The nonsegmented negative-strand RNA viruses (order Mononegavirales) include many important human pathogens. The order of their genes, which is highly conserved, is the major determinant of the relative levels of gene expression, since genes that are close to the single promoter site at the 3' end of the viral genome are transcribed at higher levels than those that occupy more distal positions. We manipulated an infectious cDNA clone of the prototypic vesicular stomatitis virus (VSV) to rearrange three of the five viral genes, using an approach which left the viral nucleotide sequence otherwise unaltered. The central three genes in the gene order, which encode the phosphoprotein P, the matrix protein M, and the glycoprotein G, were rearranged into all six possible orders. Viable viruses were recovered from each of the rearranged cDNAs. The recovered viruses were examined for their levels of gene expression, growth potential in cell culture, and virulence in mice. Gene rearrangement changed the expression levels of the encoded proteins in concordance with their distance from the 3' promoter. Some of the viruses with rearranged genomes replicated as well or slightly better than wild-type virus in cultured cells, while others showed decreased replication. All of the viruses were lethal for mice, although the time to symptoms and death following inoculation varied. These data show that despite the highly conserved gene order of the Mononegavirales, gene rearrangement is not lethal or necessarily even detrimental to the virus. These findings suggest that the conservation of the gene order observed among the Mononegavirales may result from immobilization of the ancestral gene order due to the lack of a mechanism for homologous recombination in this group of viruses. As a consequence, gene rearrangement should be irreversible and provide an approach for constructing viruses with novel phenotypes.

Animals↗
PubMed1998

Assessment of clinical performance during simulated crises using both technical and behavioral ratings.

BACKGROUND: Techniques are needed to assess anesthesiologists' performance when responding to critical events. Patient simulators allow presentation of similar crisis situations to different clinicians. This study evaluated ratings of performance, and the interrater variability of the ratings, made by multiple independent observers viewing videotapes of simulated crises. METHODS: Raters scored the videotapes of 14 different teams that were managing two scenarios: malignant hyperthermia (MH) and cardiac arrest. Technical performance and crisis management behaviors were rated. Technical ratings could range from 0.0 to 1.0 based on scenario-specific checklists of appropriate actions. Ratings of 12 crisis management behaviors were made using a five-point ordinal scale. Several statistical assessments of interrater variability were applied. RESULTS: Technical ratings were high for most teams in both scenarios (0.78 +/- 0.08 for MH, 0.83 +/- 0.06 for cardiac arrest). Ratings of crisis management behavior varied, with some teams rated as minimally acceptable or poor (28% for MH, 14% for cardiac arrest). The agreement between raters was fair to excellent, depending on the item rated and the statistical test used. CONCLUSIONS: Both technical and behavioral performance can be assessed from videotapes of simulations. The behavioral rating system can be improved; one particular difficulty was aggregating a single rating for a behavior that fluctuated over time. These performance assessment tools might be useful for educational research or for tracking a resident's progress. The rating system needs more refinement before it can be used to assess clinical competence for residency graduation or board certification.

Anesthesiology↗
PubMed1997

Oral transmucosal fentanyl citrate as an additional premedicant for adult cardiac surgery patients.

OBJECTIVE: To investigate the efficacy of a combination of midazolam and oral transmucosal fentanyl citrate (OTFC) as a preoperative medication for adult cardiac surgery patients compared with the use of midazolam alone. DESIGN: A randomized, prospective study. SETTING: University teaching hospital. PARTICIPANTS: Patients scheduled for elective coronary artery bypass surgery. INTERVENTIONS: All patients were given 50 micrograms/kg of midazolam intramuscularly in their rooms. Group I received 300 micrograms of OTFC Oralet (Anesta Corp, Salt Lake City, UT) if they weighed less than 70 kg and 400 micrograms of OTFC Oralet if they weighed more than 70 kg. Group II received a placebo Oralet. A radial artery catheter, two internal jugular venous catheters, and a pulmonary artery catheter inserted through one of the internal jugular catheters were placed in each study patient. Fentanyl was administered intravenously as a rescue drug. MEASUREMENTS AND MAIN RESULTS: Ninety percent of midazolam/OTFC patients reported feeling no pain during catheter placement, compared with 50% of midazolam/placebo patients. Fifty percent of the placebo group required fentanyl supplement of 50 micrograms intravenously because of complaints of pain, compared with 10% of the OTFC group. The midazolam/OTFC group scored approximately 20% better than the placebo group in the independent observer score of patient analgesia and the anesthesiologist rating for ease of invasive catheter placement. No myocardial ischemic events were noted in either group as determined by electrocardiogram. All patients found the Oralet mode of delivery very acceptable. CONCLUSIONS: The OTFC Oralet provides effective analgesia and sedation when combined with midazolam for invasive catheter placement in adult cardiac surgery patients. The OTFC Oralet with its gradual onset lessens the possibility of overmedicating with fentanyl, and it offers a very acceptable mode of delivery for a preemptive analgesic.

Administration, Oral↗
PubMed1997

A recombinant human adenovirus expressing the simian immunodeficiency virus Gag antigen can induce long-lived immune responses in mice.

Human adenovirus type 5 can be used as a vector to elicit immune responses to antigens expressed from heterologous DNA sequences incorporated into the viral genome, for example in mice immunized intraperitoneally. We have used a recombinant adenovirus which expresses the p55gag antigen of simian immunodeficiency virus to evaluate the nature and longevity of the response elicited when administered to mice by alterative routes which translate more readily to larger animals and man. In C57BI/6 mice immunized orally with a single dose of virus, a majority of the animals which showed evidence of responding to the immunogen by producing an anti-adenovirus response also produced a plasma antibody response to Gag which persisted for more than 1 year and a Gag-specific cytotoxic T cell response that could be detected for at least 6 months. In a minority of similarly immunized responding animals, only a cytotoxic response to Gag was observed although both humoral and cellular responses to adenovirus antigens were seen; intranasal immunization produced a Gag-specific response similar to this latter pattern. These findings suggest that delivery of adenovirus recombinants orally or intranasally may be a useful strategy for eliciting long-term cytotoxic T cell memory responses in splenocytes to candidate vaccine antigens.

Adenoviruses, Human↗
PubMed1995

The development of PCR based assays for the detection and differentiation of simian immunodeficiency virus in vivo.

Polymerase chain reaction based assays, which amplify a region of the gag gene, have been developed for the direct detection of simian immunodeficiency virus (SIV) DNA sequences in the blood of experimentally infected cynomolgus macaques. In macaques infected with a characterised virus pool (11/88 pool SIVmac 32H), an assay employing a single round of amplification was found to be highly sensitive and specific. However, in animals infected with the SIV molecular clones J5 and C8 (Rud et al., J. Gen. Virol. 75, 529-543), it was necessary to use two rounds of amplification and nested primer pairs in order to achieve sensitivity > 90%. In order to differentiate macaques infected with either of the two genetically distinct SIV clones, J5 or C8, a third PCR based assay has been developed, which amplifies a 492 bp region of the nef gene. Sequence differences between the nef genes of the two molecular clones enabled the PCR product amplified from each virus to be distinguished by restriction analysis. These sensitive and specific assays complement virological detection of SIV and enable superinfection studies to be evaluated; a prerequisite for the testing of live attenuated immunodeficiency virus vaccines.

Animals↗
PubMed1995

Prevention of hypotension after spinal anesthesia for cesarean section: six percent hetastarch versus lactated Ringer's solution.

This study was designed to determine whether preoperative administration of 6% hetastarch decreases the incidence and severity of hypotension after spinal anesthesia for cesarean section. Forty nonlaboring ASA class I and II women having nonurgent cesarean sections were randomized to receive either 500 mL of 6% hetastarch plus 1 L lactated Ringer's solution (LR) (n = 20), or 2 L of LR (n = 20) prior to induction of spinal anesthesia. Hypotension occurred in 45% of patients who received hetastarch vs 85% of those who received only LR (P < 0.05), and minimum systolic blood pressure was lower in the LR group than in the hetastarch group (85 +/- 12 vs 93 +/- 12 mm Hg [mean +/- SD]; P < 0.05). In addition, the LR group had a higher maximum heart rate (115 +/- 17 vs 104 +/- 16 bpm), a shorter mean time to hypotension (7 +/- 4 vs 10 +/- 7 min), and required more 5-mg doses of ephedrine for treatment of hypotension (0 vs 2 [median]; P < 0.05) than the hetastarch group. Neonatal outcome, as determined by Apgar scores and cord blood gas analyses, was good and similar in both groups. We conclude that 6% hetastarch plus LR is more effective than LR alone and that its routine use before spinal anesthesia for cesarean section should be considered.

Anesthesia, Obstetrical↗
PubMed1995

Immunization with class I human histocompatibility leukocyte antigen can protect macaques against challenge infection with SIVmac-32H.

OBJECTIVE: To evaluate the efficacy of immunopurified class I human histocompatibility leukocyte antigen (HLA) to protect against SIV infection. METHODS: HLA class I antigens were immunopurified from a human B-lymphoblastoid cell line. Groups of four macaques were vaccinated subcutaneously with four doses of the immunogen in adjuvant, or with adjuvant alone and subsequently challenged intravenously with 10 median monkey infectious doses of cell-free SIVmac-32H. Infection was determined by polymerase chain reaction for SIVmac proviral DNA and by virus isolation. Antigen-specific humoral and cellular immune responses were monitored. RESULTS: Macaques immunized with the HLA molecules produced anti-HLA class I antibodies that inhibited SIV replication in vitro and downregulated autologous T-cell proliferation against irradiated C8166 cells. They were partially protected (two out of four) from virus infection for at least 33 weeks when challenged with SIV grown in human cells. All four control animals were infected. CONCLUSIONS: This demonstration of partial protection, together with our previous work reporting that vaccination with allogenic cynomolgus lymphocytes can protect against challenge infection with SIV grown in simian cells, suggests that allogenic immune response induced before or during establishment of HIV infection may have important implications for AIDS disease progression.

Animals↗
PubMed1994

Fine analysis of humoral antibody response to envelope glycoprotein of SIV in infected and vaccinated macaques.

To characterize the serological response to SIV envelope, induced by vaccination with different envelope immunogens or by SIV infection, plasma samples from 11 cynomolgus macaques infected with simian immunodeficiency virus (SIV) and from 16 macaques vaccinated with three different recombinant envelope proteins were analyzed by (1) ELISA, using a variety of antigens including overlapping peptides encompassing the entire sequence of the envelope protein of SIV, and (2) competition assays, using neutralizing monoclonal antibodies to SIV gp120. Seven regions of SIV envelope were predicted to be antigenic. Peptides representing four of these, in the second and third variable regions (V2 and V3) and the fourth constant (C4) region of gp120 and the Gnann region of gp41, were recognized by the majority of sera from infected and vaccinated animals. Additional antigenic regions were identified in the first and fourth variable domains (V1 and V4) and the carboxy terminus (C5) of gp120 and in three additional regions of gp41. Most infected and vaccinated animals made antibodies that competed with the binding of the three conformational MAbs. Among the vaccinated groups, antibodies induced by vaccination with precursor glycoproteins (gp140 or gp160) recognized several additional gp120 epitopes when compared with antibodies induced by external glycoprotein gp130. Sera from infected animals showed a more restricted gp120 response (17 of 46 peptides recognized) compared to animals vaccinated with precursor glycoproteins (31 peptides recognized). The converse was true for antibodies to gp41. Sera from animals vaccinated with recombinant gp140, produced in insect cells, were the only group that failed to compete with the binding of conformational MAbs. Finally, the development of antibodies to specific epitopes of gp120 and gp41 revealed differences between long-term survivors and nonsurvivors, implying that responses to specific epitopes may be important in conferring resistance to disease progression.

Amino Acid Sequence↗
PubMed1994

Passive immunization of cynomolgus macaques with immune sera or a pool of neutralizing monoclonal antibodies failed to protect against challenge with SIVmac251.

In the first of two passive transfer experiments, three groups of four macaques were injected intraperitoneally with a normal serum pool, an immune serum pool (pool 1) collected 132-172 weeks postinfection with the 11/88 pool of SIVmac251, or with a pool of four neutralizing monoclonal antibodies (KK9, 17, 54, and 56) raised against gp120 of the 11/88 pool. Sera were given at a dose of 13 ml/kg whereas the MAb pool was given at 30 ml/kg. In a second experiment, a further four macaques were injected with an immune serum pool (pool 2) collected 12 weeks postinfection with simian-grown SIVmac251 at a dose of 19 ml/kg. Animals in both experiments were challenged with SIVmac251 grown in simian peripheral blood lymphocytes. Despite high levels of circulating antibodies in the serum of animals that received either the immune serum pools or the MAbs, all macaques became infected following challenge. The results described are in contrast to a previous report in which passive transfer of sera from animals infected with SIVsm successfully protected against challenge with the homologous virus grown in human PBMCs. Challenge with SIVmac251 grown in simian PBMCs may be the reason for these conflicting results. Nevertheless, the results suggest that in this model the presence of circulating neutralizing antibodies alone does not necessarily confer protection against challenge with SIVmac251 grown in simian cells.

Animals↗
PubMed1993

Liposomal daunorubicin treatment of HIV-associated Kaposi's sarcoma.

Compared with conventional chemotherapy, use of liposomes loaded with therapeutic agents is less toxic and more effective in experimental tumours in vivo. We have assessed efficacy and toxicity of liposomal daunorubicin (40 mg/m2 every 2 weeks) in 25 patients with HIV-associated Kaposi's sarcoma of poor prognosis. In 24 evaluable patients, there were 2 complete remissions (8.3%) and 13 partial remissions (54.2%). 5 of 11 patients with doxorubicin-resistant Kaposi's sarcoma had partial remissions. Median duration of response was 12 weeks. Quality of life improved after treatment with a response rate of 71% for physical performance and 74% for emotion. Myelosuppression was the commonest adverse event. Vomiting, stomatitis, and alopecia were rare and mild. Liposomal daunorubicin is safe and effective in HIV-associated Kaposi's sarcoma and improves quality of life. The treatment is effective even in patients resistant to other chemotherapy.

Acquired Immunodeficiency Syndrome↗
PubMed1990

3-Deazaguanine: report of a phase I trial and drug-related cardiac toxicity.

3-Deazaguanine (Dezaguanine), a purine antimetabolite, was evaluated in a phase I trial in 42 patients with advanced solid tumors. Dezaguanine was given as a weekly intravenous infusion for three consecutive weeks of a four-week cycle. The dose ranged from 30 to 2000 mg/m2; no consistent dose-limiting hematologic or gastrointestinal toxicity was observed. Some patients reported brief episodes of burning at the infusion site or transient facial flushing immediately following the administration of dezaguanine. Three patients experienced cardiac toxicity. Two patients, at doses of 1130 and 2000 mg/m2 respectively, developed congestive heart failure. In one case the heart failure was fatal; the second patient recovered within 8 weeks. The third patient had a progressive fall in left ventricular ejection fraction but did not develop clinical evidence of heart failure before his death from progressive cancer two months later. Postmortem cardiac pathology in the two patients who died early following therapy revealed nonspecific interstitial fibrosis without inflammatory cell infiltrates. The myocardium of the third patient, who died 20 months after receiving dezaguanine, was normal. Electron microscopic analysis of myocardium from the first patient did not show myofibrillar loss or mitochondrial disorganization characteristic of anthracycline cardiomyopathy. Due to the probable cardiotoxicity of dezaguanine in this study and the lack of objective antitumor response, further development of this agent has been discontinued.

Adult↗
PubMed1989

Combination chemotherapy with cytosine arabinoside (Ara-C) and cis-diamminedichloroplatinum (CDDP) for squamous cancers of the upper aerodigestive tract.

Based on the demonstration of in vitro and in vivo synergy between cytosine arabinoside (Ara-C) and cis-diamminedichloroplatinum (CDDP), we designed a Phase II trial of Ara-C plus CDDP for patients with advanced squamous cancers of the head and neck and esophagus. Sixteen patients were treated on a unique schedule of continuous-infusion Ara-C, 30 mg/m2/day over 72 h, plus CDDP, 30 mg/m2/day at hours 12, 36, and 60 of the Ara-C infusion. The objective response rate was 38% (95% confidence limits 14-62%), with two patients achieving complete clinical and radiographic response (9 and 27+ months duration) and four partial responses (median duration 4 months, range 1-7 months). There was no CDDP-related nephro- or neurotoxicities, but a flu-like syndrome of anorexia and asthenia was common. Myelosuppression was the dose-limiting toxicity, necessitating Ara-C dose adjustments in 11 cycles of therapy and leading to fatal sepsis in one patient. We conclude that the activity of this combination, though comparable to that of other CDDP-containing regimens, offers no significant therapeutic advantage, and given the excessive hematologic toxicity, should not be investigated further.

Aged↗
PubMed1989

Refractory metastatic breast cancer: salvage therapy with fluorouracil and high-dose continuous infusion leucovorin calcium.

Sixty women with metastatic breast cancer refractory to at least one chemotherapeutic regimen were treated with fluorouracil (FUra) and high-dose continuous infusion folinic acid (leucovorin calcium). One complete remission lasting 8.7 months and nine partial remissions ranging in duration from 1.3 to 12.8 months were observed, for an objective response rate of 17% (95% confidence interval for response, 8% to 27%). Nine of the ten responding patients had metastatic disease that had objectively progressed on previous chemotherapy with a FUra-containing regimen. This program was well tolerated, with toxicities consisting mainly of stomatitis and granulocytopenia. These results suggest that augmentation of the reduced folate levels of metastatic breast carcinomas may enhance the effectiveness of the fluoropyrimidines in this disease.

Adenocarcinoma↗