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Biomedical subjects

L Adams

Publications and source records attributed to L Adams.

At least 55 records · Page 3Linked to original sources
PubMed1998

REM measurements aboard MIR during 1995.

Measurements of the South Atlantic Anomaly (SAA) made with the Radiation Environment Monitor (REM) aboard Mir from November 1994 to February 1996 are presented. During this period an increase of the SAA radiation by approximately 25% is observed, which coincides with a lowering of the radio solar flux. Radio solar flux is one of the parameters controlling the earth's atmospheric distribution and with it the absorption of inner radiation belt protons forming the SAA. Due to the altitude gradient of the atmospheric density, the proton fluxes in the SAA are anisotropic (loss cone, east-west effect). The measured distribution can be accounted for by basic models.

Anisotropy↗
PubMed1998

Electrocardiographic consequences of a peripatetic lifestyle in gray wolves (Canis lupus).

Cardiac chamber enlargement and hypertrophy are normal physiologic responses to repetitive endurance exercise activity in human beings and domestic dogs. Whether similar changes occur in wild animals as a consequence of increased activity is unknown. We found that free-ranging gray wolves (Canis lupus, n = 11), the archetypical endurance athlete, have electrocardiographic evidence of cardiac chamber enlargement and hypertrophy relative to sedentary captive gray wolves (n = 20), as demonstrated by significant increases in QRS duration, QT interval, and QT interval corrected for heart rate, a tendency towards increased Q, R, and S wave voltages in all leads, and a significant decrease in heart rate. We conclude that exercise activity level and therefore lifestyle affects physiologic variables in wild animals. An immediate consequence of this finding is that physiologic measurements obtained from a captive wild-animal population with reduced exercise activity level may not accurately reflect the normal physiologic state for free-ranging members of the same species.

Adaptation, Physiological↗
PubMed1998

Metabolic activation of racemic and enantiomeric trans-8, 9-dihydroxy-8,9-dihydrodibenzo[a,l]pyrene (dibenzo[def,p]chrysene) to dibenzo[a,l]pyrene-bis-dihydrodiols by induced rat liver microsomes and a recombinant human P450 1A1 system: the role of the K-region-derived metabolic intermediates in the formation of dibenzo[a,l]pyrene-DNA adducts.

Metabolic activation studies of dibenzo[a,l]pyrene (DB[a,l]P) (dibenzo[def,p]chrysene), an extremely potent environmental carcinogen, have been focused on metabolism at the fjord region, a region associated with high mutagenic and carcinogenic activities of the corresponding fjord-region DB[a,l]P-11,12-diol-13,14-epoxides. DB[a,l]P is metabolized by beta-naphthoflavone (BNF)- and 3-methylcholanthrene-induced rat liver microsomes and a recombinant human P450 1A1 system to two major dihydrodiols, the K-region dihydrodiol, DB[a,l]P-8,9-dihydrodiol (DB[a,l]P-8,9-diol), and the fjord-region dihydrodiol, DB[a,l]P-11,12-dihydrodiol. We have investigated the further metabolic activation of DB[a,l]P-8,9-diol by BNF-induced rat liver microsomes and a recombinant human P450 1A1 system with epoxide hydrolase to DB[a,l]P-bis-diols and to DNA adducts. (+/-)-trans-DB[a,l]P-8,9-diol was synthesized and resolved into its enantiomers. Racemic trans-DB[a,l]P-8,9-diol was metabolized by BNF-induced rat liver microsomes to six metabolites: two diastereomers of trans,trans-DB[a,l]P-8,9:11,12-bis-diol, two diastereomers of trans,cis-DB[a,l]P-8,9:11,12-bis-diol, and two diastereomers of trans-DB[a,l]P-8,9:13,14-bis-diol as characterized by NMR, MS, and UV spectroscopy. Metabolic studies using both enantiomeric (-)- and (+)-trans-DB[a,l]P-8,9-diol further demonstrated that each diastereomer of trans,trans-DB[a,l]P-8,9:11, 12-bis-diol and trans-DB[a,l]P-8,9:13,14-bis-diol was comprised of two enantiomers. Similarly, incubations of enantiomeric or racemic trans-DB[a,l]P-8,9-diol with a recombinant human P450 1A1 system and epoxide hydrolase also gave the same two enantiomeric mixtures of diastereomers of trans,trans-DB[a,l]P-8,9:11,12-bis-diol and the same two enantiomeric mixtures of diastereomers of trans-DB[a,l]P-8, 9:13,14-bis-diol. This suggested that the microsomal oxidations of (-)- and (+)-trans-DB[a,l]P-8,9-diol were stereospecific. The stereospecific formation of enantiomers of trans-DB[a,l]P-8,9-diol from DB[a,l]P was examined using both BNF-induced rat liver microsomes and a recombinant human P450 1A1 system with epoxide hydrolase. Stereospecificity was observed as both metabolic systems favored the formation of (-)-trans-DB[a,l]P-8,9-diol by 8-9-fold. DNA adduct studies were undertaken using TLC/HPLC 32P-postlabeling techniques. In the presence of a recombinant human P450 1A1 system with epoxide hydrolase, DB[a,l]P gave two groups of calf thymus DNA adducts. The group of later-eluting adducts were identified as arising from syn- and anti-DB[a,l]P-11,12-diol-13,14-epoxides, while the more polar early-eluting adducts were derived, in part, from the further activation of trans-DB[a,l]P-8,9-diol. Our data indicate that, in P450 1A1-mediated microsomal incubations, DB[a,l]P is metabolized to trans-DB[a,l]P-8,9-diol which is further metabolized to DB[a,l]P-bis-diols. trans-DB[a,l]P-8,9-diol is metabolically activated to intermediates that can bind to DNA and give DNA adducts similar to those observed with DB[a,l]P. These results indicate that DB[a,l]P can be metabolically activated by both fjord-region and K-region pathways.

Animals↗
PubMed1998

Experience with a new multifunctional articulated instrument holder in minimally invasive navigated neurosurgery.

A new multifunctional articulated instrument holder for use in minimally invasive navigated neurosurgery is presented. The instrument holder is secured to the Mayfield clamp, yielding permanent fixation and guidance of instruments. Thus, surgical conditions with the advantages of both conventional and frameless stereotaxic neurosurgery are created without sacrificing the relevant advantages of both methods. Accuracy testing of the instrument holder in combination with the neuronavigation system EasyGuide Neuro demonstrated an error of 0.0 to 2.4 (mean 1.6) mm. In clinical testing, the device has been used for guided catheter insertions, pointer fixation for continuous intraoperative guidance and trajectory planning, navigated endoscopic procedures, and navigated intracerebral biopsies in totally 53 patients.

Equipment Design↗
PubMed1998

Primary-care delivery for sickle cell patients in rural Georgia using telemedicine.

BACKGROUND: Advances in newborn screening and pediatric management of sickle cell disease have resulted in patients living well into adulthood. For adults, preventive care and medication monitoring are crucial for optimal health maintenance. The Medical College of Georgia (MCG) in Augusta provides consultative services and comprehensive medical care to about 1200 sickle cell patients residing in middle and southern Georgia. An increase in the demand for clinical services in this patient population has resulted in expansion of sickle cell outreach efforts throughout the state. OBJECTIVE: A telemedicine clinic for adult sickle cell patients was established in order to meet the growing clinical demands. METHODS: An on-site outreach clinic was introduced in the target area. After 10 months of operation, a monthly telemedicine clinic was offered to patients as an option for routine medical follow-up. A clinic model was used, with scheduled appointments and a public health nurse assisting at the remote site. Phlebotomy and laboratory services enhanced the telemedicine encounter. RESULTS: Over a 12-month period, 52 encounters for 28 patients from 17 medically underserved counties were completed. All patients were African-American, and 89. 3% had Medicaid or Medicare insurance coverage or both. The clinic encounter time was 24 +/- 7.9 minutes (mean +/- SD), comparable to that for all telemedicine clinic encounters during the same period. CONCLUSIONS: The adult sickle cell population in rural Georgia accepts innovative health care delivery using telemedicine. Thus, the telemedicine sickle cell clinic has increased access to care for rural patients in underserved areas. For providers, it has allowed greater clinical productivity and diminished travel time to outreach clinics.

Adult↗
PubMed1998

Serum biochemistry of captive and free-ranging gray wolves (Canis lupus).

Normal serum biochemistry values are frequently obtained from studies of captive sedentary (zoo) or free-ranging (wild) animals. It is frequently assumed that values obtained from these two populations are directly referable to each other. We tested this assumption using 20 captive gray wolves (Canis lupus) in Minnesota, USA, and 11 free-ranging gray wolves in Alaska, USA. Free-ranging wolves had significantly (P < 0.05) lower sodium, chloride, and creatinine concentrations and significantly higher potassium and blood urea nitrogen (BUN) concentrations; BUN to creatinine ratios; and alanine aminotransferase, aspartate aminotransferase, and creatine kinase activities relative to captive wolves. Corticosteroid-induced alkaline phosphatase activity (a marker of stress in domestic dogs) was detected in 3 of 11 free-ranging wolves and in 0 of 20 captive wolves (P = 0.037). This study provides clear evidence that serum biochemical differences can exist between captive and free-ranging populations of one species. Accordingly, evaluation of the health status of an animal should incorporate an understanding of the potential confounding effect that nutrition, activity level, and environmental stress could have on the factor(s) being measured.

Animals↗
PubMed1998

A phase I and pharmacokinetic study of LY231514, the multitargeted antifolate.

LY231514 is a novel antifolate that principally inhibits thymidylate synthase, but with additional folate-dependent enzyme targets. A Phase I study of single-agent LY231514 administered as a daily i.v. infusion over 10 minutes for 5 days, repeated every 3 weeks, was conducted to evaluate the maximum tolerated dose, pharmacokinetic profile, and antitumor activity of the drug using this schedule. Thirty-eight patients with advanced malignancies that were refractory or not amenable to standard therapy were treated with a total of 116 courses of LY231514, escalating treatment doses through 10 dose levels, from 0.2-5.2 mg/m2/day. No objective clinical responses were observed, although minor antitumor activity not fulfilling the response criteria was seen in three patients. A maximum tolerated dose of 4.0 mg/m2/day was determined, with neutropenia as the predominant dose-limiting toxicity. Reversible disturbances of liver biochemistry, fulfilling the protocol definitions of dose-limiting toxicity, were also observed. Other toxicities included diarrhea, mucositis, skin rash, and fatigue. Pharmacokinetic studies were performed at all treatment levels. Analysis showed a linear relation between administered dose and both maximum plasma concentration (Cmax) and area under the plasma concentration/time curve. The drug was cleared with a day 1 total body clearance of 108.9 +/- 38.8 ml/min/m2, with plasma concentrations declining with a mean harmonic terminal half-life of 1.4 +/- 0.98 h. When given by this schedule, LY231514 is tolerable, and Phase II studies are in progress.

Adult↗
PubMed1997

Mapping of 228 ESTs and 26 genes into an integrated physical and genetic map of human chromosome 17.

We have integrated genetic and physical mapping data for chromosome 17 subdivided into 26 bins, by using a panel of chromosome 17 deletion somatic cell hybrids. One hundred four short tandem repeat and STS markers have been localized into these bins and have enabled the ordering of 288 ESTs and 26 genes, including 142 ESTs that had not been previously sublocalized on chromosome 17. The mapping information of several genetic maps, as well as information obtained by radiation hybrid and STS content mapping of YACs, has been integrated using this hybrid panel. Although existing mapping information for chromosome 17 was generally consistent for many ESTs previously mapped, the map presented here further refines the location of ESTs, as well as demonstrating a number of discrepancies found in the 17q24-q25 region. We attribute these discrepancies to the fact that the current radiation hybrid panels were selected for retention of the thymidine kinase gene at 17q25, as well as to a low concentration of YAC contigs in this region. These data illustrate the benefit of combining multiple mapping techniques to obtain the greatest accuracy. The integration of maps developed by different methods will generate the most accurate genome maps, which may then be used for the generation of large insert clone contigs for chromosome sequencing. Additionally, accurate transcript maps generated by ESTs will greatly speed the isolation of genes linked to disease loci.

Chromosome Mapping↗
PubMed1997

Localization of a growth suppressor activity in MCF7 breast cancer cells to chromosome 17q24-q25.

Chromosome 17 is one of the most frequently altered chromosomes in malignant breast cancer. At least four genes implicated in breast cancer reside on chromosome 17 (p53, 17p13; Her-2/neu/ERBB2, 17q12; BRCA1, 17q21; and nm23, 17q22). In addition, allelic imbalance has been described for at least five regions of chromosome 17. We have previously shown that the introduction of a normal human chromosome 17 into the breast cancer cell line MCF7 by microcell mediated chromosome transfer (MMCT) results in the in vitro growth arrest of these cells within 8 weeks, suggesting the presence of a growth suppressor on chromosome 17. Additionally, we have shown that the tumor suppressor gene p53 is not responsible for this phenotype, as it is wild type in MCF7 cells, and overexpression has no effect on either the in vitro or in vivo growth of these cells. We have further localized this growth suppressor gene to 17q24-q25 by transfer of chromosome 17 hybrids containing defined deletions. Whereas transfer of hybrids that contained an intact 17q (delta43/A9 and delta26/A9) resulted in growth arrest, two hybrids with overlapping deletions at 17q24-q25, had no effect on growth of MCF7 cells. Molecular analyses revealed that 50/70 (71%) of the resulting delta2/MCF7 or delta624/MCF7 MMCT clones retained an intact introduced chromosome 17. In contrast, only 8/34 (24%) of delta43/MCF7 revertants (deleted for 17p13.1-pter) which escaped growth arrest showed no breakage of the introduced chromosome 17. We did not observe a preferential loss of an intragenic BRCA1 marker in the MMCT hybrids, excluding BRCA1 as the gene responsible for this growth arrest phenotype. These data therefore implicate a new growth suppressor gene involved in breast cancer that is localized to chromosome 17q24-q25.

Breast Neoplasms↗
PubMed1997

Comparison of the clinical abrasion resistance of six commercially available denture teeth.

PURPOSE: Clinical abrasion of denture teeth has certain implications when dentures are worn in excess of the average useful lifetime. The purpose of this study was to evaluate clinical denture tooth wear over a period of 3 years. MATERIAL AND METHODS: The wear of six commercially available denture teeth (Premierdent, Acrotone, vitapan, Rx1, Duravite, and Ivoclar Orthosit) and a seventh combination of teeth was compared. Seventy patients with complete dentures were divided into seven groups of 10 each to form the study population. RESULTS: There were no significant differences among the commercial denture teeth. Porcelain/Vitapan teeth exhibited the highest amount of abrasion. Significant wear was also measured between the Ivoclar Orthosit and Porcelain/Vitapan teeth.

Acrylic Resins↗
PubMed1997

Comparison of the morphological transforming activities of dibenzo[a,l]pyrene and benzo[a]pyrene in C3H10T1/2CL8 cells and characterization of the dibenzo[a,l]pyrene-DNA adducts.

C3H10T1/2CL8 (C3H10T1/2) mouse embryo fibroblasts were used to study the in vitro carcinogenic activities of dibenzo[a,l]pyrene (DB[a,l]P) and benzo[a]pyrene (B[a]P). The morphological transforming activities of these rodent carcinogens were compared using replicate concentration-response studies. In concentration ranges where both polycyclic aromatic hydrocarbons (PAHs) were active, DB[a,l]P proved to be four to 12 times as potent as B[a]P based on concentration. At lower concentrations DB[a,l]P was active at 0.10 and 0.20 microM, concentrations where B[a]P was inactive. This makes DB[a,l]P the most potent non-methylated PAH evaluated to date in C3H10T1/2 cells. DNA adducts of DB[a,l]P in C3H10T1/2 cells were analyzed by both TLC and TLC/HPLC 32P-postlabeling methods using mononucleotide 3'-phosphate adduct standards derived from the reactions of anti-DB[a,l]P-11,12-diol-13,14-epoxide (anti-DB[a,l]PDE) and syn-DB[a,l]P-11,12-diol-13,14-epoxide (syn-DB[a,l]PDE) with deoxyadenosine 3'-monophosphate and deoxyguanosine 3'-monophosphate. All of the DNA adducts observed in C3H10T1/2 cells treated with DB[a,l]P were identified as being derived from the metabolism of DB[a,l]P to its fjord region diol epoxides through DB[a,l]P-11,12-diol. The predominant adduct was identified as an anti-DB[a,l]PDE-deoxyadenosine adduct. Other major adducts were anti-DB[a,l]PDE-deoxyguanosine and syn-DB[a,l]PDE-deoxyadenosine adducts with minor amounts of syn-DB[a,l]PDE-deoxyguanosine adducts. These DNA adduct data are consistent with similar findings of DB[a,l]PDE-deoxyadenosine adducts in mouse skin studies and human mammary cells in culture.

Animals↗
PubMed1997

Phase 1 trial of a candidate rotavirus vaccine (RV3) derived from a human neonate.

OBJECTIVE: To conduct a phase 1 safety and tolerability trial of an oral rotavirus vaccine candidate RV3 in healthy volunteers. METHODOLOGY: Double blind placebo controlled trial of a single 1 mL oral dose (6.5 x 10(5) fluorescing focus units [FFU]/mL) in 10 healthy young men, 10 3-4 year old children and 10 3 month old infants with a 4 week surveillance period. The study was undertaken at a children's hospital and nearby community in Melbourne, Australia. RESULTS: All subjects successfully completed the trial. There were no significant side-effects attributable to the vaccine preparation in any age group. No shedding of vaccine virus was detected by enzyme immunoassay. There was evidence of an immune response in serum and/or gut secretions in two of five vaccinees in each age group. CONCLUSION: RV3 rotavirus vaccine appears to be safe and well tolerated. Evidence of immunogenicity in some subjects after a single dose encourages further trials to determine immunogenicity after three doses, after reduction of viral dose, and without prior administration of buffer.

Administration, Oral↗
PubMed1997

Cerebral areas associated with motor control of speech in humans.

We have defined areas in the brain activated during speaking, utilizing positron emission tomography. Six normal subjects continuously repeated the phrase "Buy Bobby a poppy" (requiring minimal language processing) in four ways: A) spoken aloud, B) mouthed silently, C) without articulation, and D) thought silently. Statistical comparison of images from conditions A with C and B with D highlighted areas associated with articulation alone, because control of breathing for speech was controlled for; we found bilateral activations in sensorimotor cortex and cerebellum with right-sided activation in the thalamus/caudate nucleus. Contrasting images from conditions A with B and C with D highlighted areas associated with the control of breathing for speech, vocalization, and hearing, because articulation was controlled for; we found bilateral activations in sensorimotor and motor cortex, close to but distinct from the activations in the preceding contrast, together with activations in thalamus, cerebellum, and supplementary motor area. In neither subtraction was there activation in Broca's area. These results emphasize the bilaterality of the cerebral control of "speaking" without language processing.

Adult↗
PubMed1997

Metastatic carcinoid tumor imaged with CT and a radiolabeled somatostatin analog: a case report.

Radiolabeled somatostatin analogs have shown uptake in a variety of tumors. These include carcinoid, Merkel cell carcinoma, pheochromocytoma, islet cell tumor, and other tumors with somatostatin receptors. Radiolabeled somatostatin analog imaging with Indium-111-DTPA-pentetreotide permits whole body imaging, providing a new safe and effective means for detection of primary tumors and metastatic foci in neoplasms with somatostatin receptors. This imaging modality is helpful in screening the entire body as well as evaluating questionable foci of disease identified by conventional imaging modalities. This case report demonstrates the utility of computed tomography (CT) and radiolabeled somatostatin imaging as complementary modalities in the workup of a patient with metastatic carcinoid tumor.

Aged↗
PubMed1997

Evaluation of the Heart and Stroke Foundation of Canada Research Scholarship Program: research productivity and impact.

OBJECTIVE: To compare the research productivity, and its impact, of individuals awarded research scholarships from the Heart and Stroke Foundation of Canada (HSFC) with that of a parallel group of unsuccessful applicants during the funding years 1980/81 to 1989/90 inclusive. Research productivity was defined as the number of peer reviewed publications, and impact was evaluated from the number of publications cited; the number of citations per publication; the number of citations per individual; and the impact score. STUDY SELECTION: Data were collected on 192 individuals. Cohorts were defined as successful and unsuccessful individuals entering the system in the same year. The study comprised 10 separate cohorts. Data were collected on yearly publications and citation counts for each individual. These data, along with journal impact factors, were obtained from the Institute for Scientific Information. CONCLUSIONS: During the 10 years of the study, individuals funded by the HSFC published more papers, more of their papers were cited, and they received more citations per individual than the unfunded comparison group. This consistency in multiple indicators provides strong evidence that funded individuals are more productive and that their work has a greater impact on the body of knowledge in this area. Although this study cannot unequivocally show a direct causal relation between funding and research success, the trend as shown by the indicators studied suggests a beneficial effect.

Analysis of Variance↗