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Biomedical subjects

N Anderson

Publications and source records attributed to N Anderson.

At least 127 records · Page 7Linked to original sources
PubMed1991

Cardiovascular and catecholamine responses to head-up tilt in the diagnosis of recurrent unexplained syncope in elderly patients.

To increase understanding of the mechanisms causing syncope in patients over the age of 60, hemodynamic and hormonal responses to 60 minutes of 60 degree head-up tilt were examined in 10 patients with recurrent syncope of unknown origin and five controls with no history of syncope. Nine of 10 patients and all five controls experienced orthostatic intolerance on the tilt table. Syncope or pre-syncope occurred later in controls than in those syncope patients who had exact reproduction of their clinical symptoms (median time 52 versus 22 minutes, P = 0.05). Three different mechanisms of orthostatic intolerance were identified in the 14 subjects: (1) vasovagal syncope, n = 9 (sudden hypotension +/- bradycardia); (2) dysautonomic syncope, n = 3 (immediate and gradual parallel declines in both systolic and diastolic pressures with blunted increase in heart rate); (3) psychogenic or vestibular reaction, n = 2 (orthostatic intolerance without hemodynamic changes). Vasovagal syncope patients showed a significant increase in plasma norepinephrine from baseline to maximum level during tilt (100 +/- 39% increase, P = 0.03) and a subsequent decrease at the time of syncope (30 +/- 5% decrease, P = 0.01), while plasma epinephrine increased markedly from baseline to the time of syncope (827 +/- 154% increase, P = 0.0003). Dysautonomic syncope patients had lower supine levels of norepinephrine compared to vasovagal syncope patients (182 +/- 30 versus 614 +/- 146 pg/mL, P = 0.008) and no significant change in norepinephrine over time; epinephrine levels increased significantly less than in vasovagal patients (net change 38 +/- 8 versus 189 +/- 56 pg/mL, P = 0.008).(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1991

Active fixation leads--long-term threshold reduction using a drug-infused ceramic collar.

Previous investigators, including our group, have reported the threshold reduction benefits of steroid-releasing leads. To date, all published literature has been for the passive fixation versions. The application of steroids should also enhance the performance of active fixation leads. We have developed and tested an atrial and a ventricular Accufix lead with a dexamethasone acetate-releasing, porous ceramic collar (DA DEC). A long-term sheep study has shown a significant reduction in thresholds (THR) when compared to standard Accufix leads without the collar (ACC) for atrial (ATR) and ventricular (VENT) versions (bipolar THR [0.5 msec] at 24 weeks: VENT DA DEC = 0.51 +/- 0.07, VENT ACC = 1.49 +/- 1.03; ATR DA DEC = 1.31 +/- 1.14, ATR ACC = 2.99 +/- 1.31). All other parameters tested, including pacing and sensing impedance as well as polarization overpotential, were similar for the two groups. The Accufix DEC leads therefore have excellent potential for low energy stimulation.

Aluminum Oxide↗
PubMed1991

The efficacy of mixtures of albendazole sulphoxide and levamisole against sheep nematodes resistant to benzimidazole and levamisole.

Faecal egg count reduction tests and an anthelmintic efficiency assay were used to assess the efficacy of combinations of albendazole sulphoxide and levamisole against populations of Ostertagia and Trichostrongylus sp. which contained different proportions of worms resistant to both benzimidazole and levamisole anthelmintics. Compared to the effects of either drug alone, significantly greater efficacy was obtained using combinations which included dose rates similar to those recommended for the separate components. At these dose rates, the mixtures reduced mean faecal egg counts by 95% or more, and caused a reduction of 68% in adult Ostertagia sp. and more than 95% for 4th stage Ostertagia and T colubriformis. The increased efficacy of the mixtures could be accounted for by actions of the drugs acting independently.

Albendazole↗
PubMed1991

Field evaluation of a mixture of albendazole sulphoxide and levamisole against Ostertagia and Trichostrongylus spp in sheep.

The efficacy of a mixture of albendazole sulphoxide and levamisole, 3.6 and 8.25 mg/kg respectively, at single and double dose rates, was compared with the recommended dose rate of each anthelmintic alone. The comparison was conducted on groups of 6 to 14-week-old lambs on 22 farms, 16 of which had evidence of multiple resistance to benzimidazole and levamisole. A single dose of the mixture reduced mean egg counts by 95% on half the farms with multiple resistance and on all the remaining farms. Consequently, the mixture should be included in an assessment of effective anthelmintics on farms to determine its value for nematode control. A double dose rate of mixture was effective on all but 4 farms. Reductions caused by the mixture were due to the additive actions of the drugs on 18 of 22 farms; synergistic action was noted on only 3 farms. It was concluded that the mixture of albendazole sulphoxide and levamisole offered many farmers an effective anthelmintic for use in preventive control programs. Recommendations for such programs include annual rotation of effective anthelmintics as a means of delaying selection for drug resistance.

Albendazole↗
PubMed1991

Phage typing of Staphylococcus intermedius.

Staphylococcus intermedius, a coagulase-positive staphylococcal species, is a common canine pathogen and a rare human wound pathogen. A total of 145 strains of S. intermedius (ATCC 29663, 4 reference strains, 4 human isolates, 44 canine infection isolates, and 92 isolates from canine gingiva) were screened for lysogenic phage by a modified Fisk method. Nineteen phage preparations were prepared for preliminary typing experiments. Lytic activity was observed on 93 of 145 (64.1%) isolates, yielding 44 lytic patterns with individual strains susceptible to one or more phages. Five phages lysed only a single strain, but lytic patterns varied from 1 to 11 lytic phages per isolate. A distinct lytic pattern did not separate canine or human wound isolates from canine gingival isolates. All human wound isolates fell into the two most common canine gingival or wound patterns; the single human nasopharyngeal isolate was not lysed by any phage. Twenty-two of 44 (55%) canine wound isolates and 65 of 92 (71%) gingival isolates yielded lytic patterns. Lysogenic phages are common in S. intermedius. This preliminary study suggests that phage typing may be a useful tool in distinguishing epidemiologically related strains.

Animals↗
PubMed1990

Bilateral breast cancer after cured Hodgkin's disease.

Three patients developed bilateral breast cancer at 10 to 24 years after mantle irradiation for locally or systemically advanced Hodgkin's disease (HD). Four of the six cancers in the three patients were detected only by mammography. Pathologically, five of the cancers were intraductal carcinomas (four with an invasive component) with one being a lobular carcinoma. Five of the six lesions were Stage I pathologically without evidence of axillary nodal involvement. It is recommended that female patients with Hodgkin's disease who have received mantle irradiation as part of the therapy for their Hodgkin's disease and who are observed for 10 or more years after completion of mantle irradiation be considered at risk for the development of breast cancer. Such patients should be monitored appropriately by routine bilateral mammograms to increase the early detection of early stage lesions.

Adult↗
PubMed1990

General assay for phosphoproteins in cerebrospinal fluid: a candidate marker for paraneoplastic cerebellar degeneration.

The components of protein phosphorylation systems (protein kinases, protein phosphatases, and their phosphoprotein substrates) are highly enriched in neuronal cells compared with other cell types. We exploited this relative neuronal enrichment of protein phosphorylation system components to develop a general assay technique for putative protein kinase substrates (phosphoproteins) in human cerebrospinal fluid. Using this cerebrospinal fluid phosphoprotein assay, we have detected a putative protein kinase C substrate protein of apparent Mr 60 kd in 6 of 14 patients with paraneoplastic cerebellar degeneration but not in any of 55 patients with a variety of other neurological diseases. Phosphoproteins in cerebrospinal fluid may provide novel and unique markers for the diagnosis or staging of neuronal diseases as well as offer potential insights into the biochemical characterization of affected neuronal populations.

Adult↗
PubMed1990

Drug-eluting collar--a new approach to reducing threshold.

This study evaluated the clinical performance of leads with a drug-eluting (less than 0.5 mg of dexamethasone sodium phosphate) collar (DEC) placed adjacent to a 4-mm2 Pt/Ir coated electrode (Telectronics model 030-368). Ten trailing tined ventricular silicone DEC leads and ten control leads (model 030-359) were implanted transvenously in patients of comparable age, sex, and indication for pacing. Early threshold rise, chronic thresholds (Vario), and lead impedances were monitored by pacer telemetry. The DEC lead had substantially lower thresholds in the first few weeks (P less than 0.0005) as well as chronically (P less than 0.025). The study has shown that a drug dose of less than 0.5 mg, released from a drug-eluting collar (DEC), is effective in reducing thresholds.

Aged↗
PubMed1990

In vivo elution rate of drug eluting ceramic leads with a reduced dose of dexamethasone sodium phosphate.

We have evaluated the in vivo elution rate and the threshold voltage performance of a new lead incorporating a controlled delivery device based on a porous ceramic collar. The drug, dexamethasone sodium phosphate (DSP less than 0.2 mg), was contained within the pores of a ceramic collar that was positioned externally and adjacent to a 4 mm2 Pt/Ir coated electrode. Thirty-three leads comprising a porous ceramic drug eluting collar (DEC) were implanted in the right ventricle of 12 sheep. In vivo elution was determined by analyzing the drug remaining in the collar after 1, 3, 11, and 28 days. Voltage thresholds were measured at implant and then weekly for 28 days on three sheep. Results were compared to leads with identical electrodes but with silicone DEC (DSP less than 0.5 mg). The in vivo elution rate of the ceramic DEC leads was fast with approximately 50% of the drug content on the first day. Although the drug content and elution rates were different for the ceramic and silicone DEC leads, the threshold performance of the leads was similar. For ceramic and silicone DEC leads, threshold voltages at implant and at 4 weeks were 0.29 +/- 0.09 compared to 0.37 +/- 0.08 and 0.42 +/- 0.08 compared to 0.44 +/- 0.13, respectively. The results show that a relatively rapid release of a reduced dose of DSP from a DEC is still effective in reducing threshold peaking.

Animals↗
PubMed1990

Separation of cough and reflex bronchoconstriction by inhaled local anaesthetics.

Cough and airway constriction are common features of respiratory diseases. Both can be caused by stimulation of airway nerves. We have studied the effects of airway anaesthesia on these reflexes, stimulated by inhaled capsaicin, in order to determine whether they are controlled by the same sensory nerves. Ten volunteers had capsaicin cough dose responses performed before and at 10 min after inhaling placebo (ascorbic acid in saline), and the topical anaesthetics lignocaine 40 mg, and dyclonine 8 and 4 mg. The effect of the drugs on respiratory resistance (Rrs), measured using a forced oscillation technique, was measured both before and after the inhalation of a dose of capsaicin which caused less than two coughs. Lignocaine (40 mg) and dyclonine (8 mg) caused significant reports of oral anaesthesia but only lignocaine reduced the cough response to inhaled capsaicin, increasing the log dose of capsaicin causing three or more coughs by 162%. None of the treatments altered basal Rrs or its increase after inhaled capsaicin. Thus, the cough and reflex bronchoconstriction caused by inhaled capsaicin have different sensitivities to inhaled local anaesthesia, suggesting that the effect may be mediated by different sensory pathways.

Administration, Inhalation↗
PubMed1989

Structure of the bovine elastin gene and S1 nuclease analysis of alternative splicing of elastin mRNA in the bovine nuchal ligament.

Genomic clones encompassing all the translated sequences, the 3' untranslated sequence, and 1 kb flanking the ATG translation initiation codon of bovine tropoelastin have been obtained and characterized by restriction enzyme analysis and extensive DNA sequencing. These analyses demonstrated that functionally distinct hydrophobic and cross-linking domains of the protein are segregated into separate exons throughout the gene. The putative promoter region lacks a TATA box, has an extremely high G+C content, and contains several SP1 binding sites. Comprehensive S1 analyses using probes covering the entire mRNA and RNA isolated from the nuchal ligament of bovine fetuses of different ages, neonate calves, and adult cows demonstrated that while only a single exon is alternatively spliced at high frequency, many exons are alternatively spliced at limited, variable frequencies. The results also suggest that such limited splicing is increased in the adult tissue relative to fetal and neonate tissues.

Amino Acid Sequence↗
PubMed1989

Etoposide admixed with cisplatin. Phase I clinical investigation of 72-hour infusion.

The compatibility of etoposide (VP-16-213) and cisplatin (CDDP) in an admixture solution was established by High Pressure Liquid Chromatography (HPLC) studies in vitro at room temperature. A Phase I dual-dose escalation study of the admixture was subsequently carried out utilizing a 24-hour continuous infusion schedule administered for 3 consecutive days and repeated at 3 to 4 week intervals. Twenty-seven patients received a total of 42 treatment courses. The daily dose rates for VP-16-213 were 50, 75, and 100 mg/m2/day. Cisplatin was delivered at 20, 30, and 40 mg/m2/day for each dose level of VP-16-213. Dose-rate limiting toxicity was observed first at the VP-16 dose of 50 mg/m2/day and CDDP at 30 mg/m2/day. At 100 mg/m2/day for VP-16-213, six of 17 courses were associated with life-threatening leukopenia and four of six patients died with sepsis. All but one of the patients developing severe or life-threatening leukopenia had associated acute renal failure with serum creatinine levels greater than 2 mg/dl. The optimal dose rate of delivery for VP-16 and CDDP administered as a 72-hour infusion admixture is 75 mg/m2/day and 30 mg/m2/day, respectively.

Adult↗
PubMed1989

Cyclophosphamide, methotrexate, and 5-fluorouracil in a three-drug admixture. Phase I trial of 14-day continuous ambulatory infusion.

The compatibility and stability at room temperature for up to 7 days of a three-drug admixture of cyclophosphamide, methotrexate, and 5-fluorouracil (5-FU) (CMF) was established permitting the practical delivery of the combination as an infusion in an ambulatory setting. Fourteen patients received 20 courses of CMF administered on a continuous infusion schedule for 14 days of a 28-day cycle. The dose rates were fixed for 5-FU (300 mg/M2/day) and methotrexate (0.75 mg/M2/day). The cyclophosphamide dose was escalated from 25 to 50, 75, and 100 mg/M2/d. Leukopenia and thrombocytopenia were observed in two of five patients receiving the maximal dose of cyclophosphamide. No other toxicities were observed including alopecia, stomatitis or liver function abnormalities. This Phase I trial suggests that the cumulative doses of cyclophosphamide, methotrexate, and 5-FU are comparable to the maximum doses delivered as single agent infusions. Furthermore, when the infusion CMF is compared to the "standard" bolus schedule for CMF, the infusion schedule delivers 116%, 8%, and 350% of the respective three component drugs (cyclophosphamide, methotrexate, and 5-FU).

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1989

Combined 5-fluorouracil and floxuridine administered as a 14-day infusion. A phase I study.

5-Fluorouracil (5-FU) and floxuridine (FUdR) were admixed in a single solution and administered via a central venous catheter on a continuous infusion schedule for 14 days. The Phase I trial design developed for admixture combinations was employed with starting doses for 5-FU at 250 mg/m2/day and for FUdR at 0.075 mg/kg/day. Twenty patients and 28 courses were studied. Dose rate limiting toxicity was pseudoregional enteritis with or without stomatitis experienced by five of ten of the courses administered at the highest dose rates of the admixture components. The simultaneous delivery of the two agents results in a modest compromise of the cumulative dose delivered for FUdR. Previous Phase I studies of single agent 5-FU and FUdR had demonstrated that the optimal dose rates for the individual agents in a 14-day continuous 24-hour infusion schedule is 350 mg/m2/d and 0.125 mg/Kg/day, respectively. The maximum dose rate of 5-FU at 350 mg/m2/day for 14 days is not restricted even with the addition of FUdR at up to 0.1 mg/kg/day. The optimal dose rates for Phase II trails should be as follows: 5-FU, 350 mg/m2/day; and FUdR, 0.1 mg/kg/day.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1989

A phase I clinical trial of combined fluoropyrimidines with leucovorin in a 14-day infusion. Demonstration of biochemical modulation.

Two consecutive Phase I trials of continuous infusion 5-fluorouracil (5-FU) or floxuridine (5-FUdR) admixed with leucovorin (LCV) were performed and involved 19 and 24 patients, respectively. The studies were carried out to identify the optimal dose rate of delivery for the two admixtures (5-FU + LCV and 5-FUdR + LCV) administered for 14 days, and to determine if biochemical modulation could be identified. The optimal dose rates for 5-FU plus LCV were 200 mg/m2/d and 5 mg/m2/d, respectively. The optimal dose rates for 5-FUdR plus LCV were 0.075 mg/kg/d and 5 mg/m2/d, respectively. The dose rate limiting toxicity for 5-FU plus LCV was stomatitis and for 5-FUdR plus LCV it was diarrhea. LCV administered as an admixture with either 5-FU or 5-FUdR on an infusion schedule decreases the optimally tolerated dose rates for these two agents to 83% and 60%, respectively. This is achieved with low-dose LCV infusions.

Adult↗
PubMed1989

Detecting benzimidazole resistance with faecal egg count reduction tests and in vitro assays.

Composite strains of Trichostrongylus colubriformis and Ostertagia spp consisting of 0, 1, 10, 25, 50, 75, 90, and 100% of known resistant strains were prepared and tested for benzimidazole resistance using faecal egg count reduction tests, in vitro egg hatch assays and tubulin binding assays. All tests detected resistance where the proportion of the resistant strain in the composite was 50% or more, whereas none of the tests unequivocally detected resistance below 25%. Egg count reduction tests were no less sensitive than the in vitro tests in detecting low levels of resistance but the egg hatch and tubulin binding assays provided a better quantitative estimate of moderate to high levels of resistance. Faecal egg count reduction therefore, provides a suitable means of detecting resistance in the field but tests, more sensitive to low levels of resistance are required. Results indicate that the use of post-treatment counts alone provides an adequate indication of anthelmintic efficiency.

Albendazole↗