Biomedical subjects

N Anderson

Publications and source records attributed to N Anderson.

At least 19 recordsLinked to original sources

PubMed1995

Use of pedicled fat pad graft as an adjunct in the reconstruction of palatal cleft defects.

The purpose of this article is to provide the rationale for the use of pedicled buccal fat pad grafts as an adjunct to the reconstruction of palatal or dentoalveolar clefts in cases when healing by secondary intention may need to be considered and integrated into the initial treatment plan because of the size of the defect or qualitative or quantitative tissue constraints. Four representative cases are presented in which a pedicled buccal fat graft was adjunctively used in conjunction with pedicled mucosal flaps to gain closure of large oroantral or oronasal cleft deformity.

Adipose Tissue↗

PubMed1992

Controversial issues in 5-fluorouracil infusion use. Dose intensity, treatment duration, and cost comparisons.

BACKGROUND: The use of ambulatory infusions of 5-fluorouracil (5-FU) improves the therapeutic index of this drug and is superior to the traditional schedule of bolus administration weekly or daily for 5 days at 5-week intervals. The infusion schedules that have been used vary as follows: (1) 24-hour infusion weekly; (2) 48-hour infusion weekly or biweekly; (3) 120-hour infusion at 4-5-week intervals; (4) 14-day infusion; and (5) protracted infusions continuously for 10 weeks or more. The relationship of dose intensity to infusion duration and the analysis of costs of chemotherapy were reviewed. METHODS: Selected clinical trials of infusional 5-FU were analyzed regarding infusion duration and dose intensity in relationship to response rates (RR). Chemotherapy cost was analyzed distinguishing "cost" definitions. RESULTS: The response rates for the infusion durations studied in Phase II and III trials were: (1) 24 hours, 25%; (2) 48 hours, 30%; (3) 120 hours, 3%; (4) 14-day, 12%; and (5) 10 weeks, 30%. The corresponding DI for each infusion duration was (1) 24 hours, 2.6 g/m2/week; (2) 48 hours, 2.4 g/m2/week; (3) 120 hours, 1.25 g/m2/week; (4) 14-days, 1.225 g/m2/week; and (5) 10 weeks, 2.1 g/m2/week. Cost analysis by actual reimbursement was compared for 5-FU infusion and bolus 5-FU with leucovorin (high and low dose) and 5-FU with interferon. Monthly reimbursement for each is $1400, $2000, and $1150, and up to $3000, respectively. CONCLUSIONS: DI and infusion duration have a complex interaction that may contribute meaningfully to the therapeutic index, but this issue can only be resolved by randomized clinical trials. The cost of 5-FU infusion is comparable to that of bolus therapy when leucovorin or interferon are added in combination. Considering the relative absence of patient toxicity, the costs of 5-FU infusion are substantially less than bolus delivery.

Costs and Cost Analysis↗

PubMed1992

Etoposide plus carboplatin admixture. Phase I study of five- or seven-day continuous infusion.

Thirty-five patients were entered in a Phase I trial of an admixture infusion of etoposide (VP-16) and carboplatin (CBDCA) administered continuously for 5 or 7 days. Because of the compatibility and solubility of the two agents, the treatment program could be administered on an outpatient basis. The dose rate of VP-16 was fixed at 30 mg/m2/day (total dose 150 mg/m2 for 5 days or 210 mg/m2 for seven days) for each cycle. Carboplatin was evaluated at three dose rates: 50, 60, and 75 mg/m2/day on the 5-day infusion and 40, 50, and 60 mg/m2/day on the 7-day infusion with cycles repeated at 28 to 42 days. The dose limiting toxicity was hematologic and followed a pattern typical for carboplatin, that is, delayed neutropenia and/or thrombocytopenia with a protracted leukocyte recovery. Renal toxicity was observed in three patients. The optimum total dose for the infusional carboplatin component was 300 mg/m2 (5-day) and 420 mg/m2 (7-day). The total etoposide dose was 150 mg/M2 and 210 mg/M2, which did not appear to contribute to the hematologic toxicity. Delivery of the admixture of VP-16 and CBDCA was feasible, although cumbersome, as a result of the portable delivery system. Extending the duration of infusion increases the total cumulative dose of carboplatin and etoposide that can be administered without increasing adverse effects.

Aged↗

PubMed1992

Systemic and mucosal antibodies to Klebsiella in patients with ankylosing spondylitis and Crohn's disease.

Whole gut lavage fluid is a useful source of material for the study of intestinal immunity and inflammation in humans. Systemic and mucosal antibodies to Klebsiella pneumoniae were measured by enzyme linked immunosorbent assay (ELISA) in serum samples and whole gut lavage fluid from 14 patients with ankylosing spondylitis, 14 with Crohn's disease, and 16 immunologically normal controls. As the concentration of IgG in whole gut lavage fluid reflects disease activity in Crohn's disease, this approach was used to detect intestinal inflammation in patients with ankylosing spondylitis who also had disease activity and use of non-steroidal anti-inflammatory drugs (NSAIDs) recorded. Small intestinal permeability to cellobiose and mannitol was also studied. In serum samples, levels of IgA antibody to klebsiella were high in patients with Crohn's disease and in patients with active ankylosing spondylitis, and were significantly correlated with the erythrocyte sedimentation rate in patients with ankylosing spondylitis. Levels of IgG antibody to klebsiella were also high in patients with Crohn's disease. Studies of whole gut lavage fluid showed similar levels of IgA antibody to klebsiella in the three study groups, but levels of whole gut lavage fluid IgM and IgG antibodies to klebsiella were high in patients with Crohn's disease. Levels of IgG in whole gut lavage fluid were high in patients with Crohn's disease but in only one patient with ankylosing spondylitis, though the cellobiose/mannitol permeability ratio was abnormal in eight of 13 patients with ankylosing spondylitis. It is concluded that high levels of serum IgA antibody to klebsiella are not specific to ankylosing spondylitis, and that there is no evidence of an abnormal intestinal IgA antibody response to klebsiella in patients with ankylosing spondylitis.

Adult↗

PubMed1991

Dual modulation of 5-fluorouracil using leucovorin and hydroxyurea. A phase I trial.

Oral hydroxyurea (HU) was added to a regimen of 5-fluorouracil (5-FU) plus leucovorin (LCV) administered as a continuous 24-hour infusion for 14 days. A previous report of the 5-FU plus LCV infusion established optimal dosages of 200 mg/m2/d and 5 mg/m2/d, respectively, for each agent. Oral HU was added to the regimen in total dosages of 0.5 g/d, 1.0 g/d, 1.5 g/d, or 2.0 g/d. Twenty-two patients received a total of 45 courses of treatment. Stomatitis was the dose-limiting side effect; it occurred in 3 of 14 courses with HU at 0.5 g/d (21%) and 9 of 17 courses with HU at 1.0 g/d (53%). Dosage escalation to 1.5 g/d or 2.0 g/d was possible in only 3 of 22 patients (17%). The median time to stomatitis was 10 days (range, 7 to 12 days). One response was observed in this heavily pretreated population. Phase II trials of HU plus LCV dual modulation of infusional 5-FU should use initial HU dosages of 0.5 g/d for the 14-day regimen described, with dose escalation as tolerated. Variable oral absorption presumably accounts for the small group of patients who can tolerate the higher doses of HU.

Administration, Oral↗

PubMed1991

Infusional carboplatin. Phase I studies of 5-day and 14-day infusions.

Twenty-two courses of carboplatin (Paraplatin; Bristol-Meyers, Evansville, IN) (CBDCA) were administered to 15 patients with advanced cancer on a continuous 24-hour per day infusion schedule for either 5 days or 14 days. The objective of the trial was to establish the optimal dose rate and cumulative dose for this treatment schedule. The dose-limiting toxicity was myelosuppression, with leukopenia and thrombocytopenia observed. The optimal dose rate for the 5-day infusion was 75 mg/m2/d or a total cumulative dose of 375 mg/m2/d. The optimal dose rate for the 14-day infusion was 25 mg/m2/d or a total cumulative dose of 350 mg/m2/d. The times to nadir levels of leukocyte and platelet counts were 34 days and 25 days, respectively, with a median time to recovery of 14 days and 7 days, respectively, in patients with Grade 3 or greater marrow suppression. The pattern of hematologic toxicity with infusional CBDCA is comparable to that seen with bolus schedules. There is, therefore, no clinical advantage of the infusional schedule for CBDCA in terms of toxicity and the dose delivered per cycle, and the dose intensity is slightly less than with a bolus schedule. If there is a therapeutic advantage for the infusional schedule, a prospective comparative trial against the standard bolus schedule will be required to establish it. Bolus and infusional schedules for CBDCA are associated with a delayed pattern of thrombocytopenia and prolonged leukopenia, necessitating 5 or more weeks between treatment cycles.

Aged↗

PubMed1991

Ifosfamide continuous infusion without mesna. A phase I trial of a 14-day cycle.

Twenty patients received 27 courses of ifosfamide administered as a 24-hour continuous infusion for 14 days without Mesna. The goal of the study was to deliver a dose rate and total cumulative dose of ifosfamide that would be comparable to standard bolus or short-term infusions administered with Mesna. Dose escalations proceeded from 200 to 300, 400, 450, 500, and 550 mg/m2/d. Four patients developed transient microscopic hematuria at 400, 450, and 500 mg/m2/d. There were no instances of macroscopic hematuria. At 550 mg/m2/d, three patients experienced nonurologic toxicity; confusion (1), nausea (1), and Grade 2 leukopenia (1). The recommended dose of 500 mg/m2/d delivers a total dose of 7 g/m2 per cycle, which is comparable to that delivered in clinical practice for bolus or short-term infusion. Because few patients received multiple courses over time, the cumulative effects are indeterminate in the present trial. The frequency and predictability of hematuria are not precise, and at least daily monitoring by urine Hematest is essential, adding Mesna to the infusate in patients with persistent hematuria. The protracted infusion schedule for ifosfamide permits convenient outpatient administration without Mesna and reduces the drug cost of clinical usage of this agent by up to $890 per cycle. Clinical activity was demonstrated in a single patient, but a comparative trial of standard bolus schedules with the protracted infusion schedule will be necessary to determine if the clinical effectiveness of the drug is maintained.

Adult↗

PubMed1991

Colonoscopically detected colorectal cancer missed on barium enema.

The radiographs and clinical records of 26 patients with colorectal cancer missed on barium enema, and subsequently detected at colonoscopy, were reviewed to determine the cause of radiological error. Twenty (77%) of the patients were female. In 24 of 26 patients, anemia and/or rectal bleeding was a presenting feature. Fourteen of the 26 (54%) missed cancers were in the sigmoid colon, 10 (38%) in the ascending colon or hepatic flexure, and two (8%) in the rectum. Tumor size ranged from 20-100 mm. Fifteen were polyps, and 11 annular cancers. Fourteen (54%) were Dukes C or D tumors. Twenty-eight barium enemas in 23 patients were available for review: 86% were double-contrast studies. In 18 (76%), the cancer could be seen in retrospect and, in over half, the tumor was obvious. The dominant perceptive error was due to missing the lesion in the barium pool. Other major errors were missing the lesion en face or in overlapping loops. As most cancers were missed because of observer perceptive error, by both experienced and inexperienced radiologists, the authors recommend double reporting of all barium enemas.

Aged↗

PubMed1991

Infusion of floxuridine plus etoposide plus cisplatin in human malignancies.

36 patients with advanced malignancy were studied in a phase I trial of continuous 24-h infusion of floxuridine (FUdR) plus etoposide plus cisplatin (FEP) administered for 5 consecutive days at 4-week intervals. Study design fixed the dose rate of etoposide and cisplatin with escalation of FUdR only. Dose rate-limiting toxicity related to the FUdR component was stomatitis and diarrhoea and was invariably associated with leukopenia and thrombocytopenia when grade 3 or 4 level gastrointestinal toxicity was observed. Only 3 of 64 courses were associated with transient renal failure related to cisplatin. Drug-related deaths occurred (leukopenia-associated sepsis) in 4 patients with poor performance status (ECOG 3 and 4). Responses occurred in 15 of 26 evaluable patients (all previously treated minimally or untreated) including 5/11 non-small cell lung cancer; 3/3 oesophageal; 2/2 breast; 4/5 gastric; 1 osteogenic sarcoma; and 1 unknown primary (probably ovary). The recommended dose rates for a 5-day infusion of the three agents for good risk patients is 20 mg/m2 per day of each drug. For poor risk patients including age greater than 65 years; performance status 2 or greater; or extensive bone metastases or prior radiation; the recommended starting dose rates are: FUdR 15 mg/m2 per day; etoposide 15 mg/m2 per day; and cisplatin 20 mg/m2 per day. Dose escalation of FUdR to a maximum of 25 mg/m2 daily is feasible in selected patients demonstrating optimal tolerance.

Adult↗

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↗