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Biomedical subjects

J Hanson

Publications and source records attributed to J Hanson.

At least 73 records · Page 4Linked to original sources

Edmonton Regional Palliative Care Program: impact on patterns of terminal cancer care.

The Edmonton Regional Palliative Care Program was established in July 1995 to measure the access of patients with terminal cancer to palliative care services, decrease the number of cancer-related deaths in acute care facilities and increase the participation of family physicians in the care of terminally ill patients. In this retrospective study the authors compared the pattern of care and site of deaths before establishment of the program (1992/93) and during its second year of operation (1996/97). Significantly more cancer-related deaths occurred in acute care facilities in 1992/93 than in 1996/97 (86% [1119/1304] v. 49% [633/1279]) (p < or = 0.001). The number of inpatient days decreased, from 24,566 in 1992/93 to 6960 in 1996/97. More cancer patients saw a palliative care consult team in 1996/97 than in 1992/93 (82% v. 22%). The shift from deaths in acute care facilities to palliative hospices suggests that the establishment of an integrated palliative care program has increased access of patients with terminal cancer to palliative care.

Alberta↗

Setup reproducibility in radiation therapy for lung cancer: a comparison between T-bar and expanded foam immobilization devices.

PURPOSE: Physiologic and non-physiologic tumor motion complicates the use of tight margins in three-dimensional (3D) conformal radiotherapy. Setup reproducibility is an important non-physiologic cause of tumor motion. The objective of this study is to evaluate and compare patient setup reproducibility using the reusable T-bar and the disposable expanded foam immobilization device (EFID) in radiation therapy for lung cancer. METHODS AND MATERIALS: Two hundred forty-four portal films were taken from 16 prospectively accrued patients treated for lung cancer. Patients were treated with either a pair of anterior and posterior parallel opposing fields (POF), or a combination of POF and a three-field isocentric technique. Each patient was treated in a supine position using either the T-bar setup or EFID. Six patients were treated in both devices over their treatment courses. Field placement analysis was used to evaluate 3D setup reproducibility, by comparing positions of bony landmarks relative to the radiation field edges in digitized simulator and portal images. Anterior-posterior, lateral, and longitudinal displacements, as well as field rotations along coronal and sagittal planes were measured. Statistical analyses of variance were applied to the deviations among portal films of all patients and the subgroup treated with both immobilization methods. RESULTS: For the T-bar immobilization device, standard deviations of the setup reproducibility were 5.1, 3.7, and 5.1 mm in the anterior-posterior, lateral, and longitudinal dimensions, respectively. Rotations in the coronal plane and the sagittal plane were 0.9 degrees and 1.0 degrees, respectively. For the EFID, corresponding standard deviations of set up reproducibility were 3.6 mm, 5.3 mm, 5.4 mm, 0.7 degrees and 1.4 degrees, respectively. There was no statistically significant difference (p = 0.22) in the 3D setup reproducibility between T-bar and EFID. Subgroup analysis for the patients who were treated with both immobilization devices did not reveal a difference either. There was no consistent systematic error from simulator to treatment unit identified for either immobilization device. CONCLUSION: Although the optimal immobilization technique and patient positioning for thoracic radiotherapy have yet to be determined, this study indicates that T-bar is comparable with EFID in its setup reproducibility. In view of the inherent advantages of T-bar, it has become a standard immobilization device at our institution. The observed range of displacements in field positioning with either immobilization device implies that one cm (two standard deviations [SD] of setup error) will be a more appropriate margin to allow for setup variability in radiation therapy for lung cancer.

Equipment Design↗

The use of intermittent subcutaneous injections of oxycodone for opioid rotation in patients with cancer pain.

Oxycodone is a strong opioid that has been available for at least 70 years. At present, commercially prepared parenteral oxycodone is only available in Finland. We report in this paper our experience of administering oxycodone s.c. From 21 October 1996 to 31 July 1998, 63 advanced cancer patients received intermittent s.c. injections of oxycodone via the Edmonton Injector, a simple, low-cost mechanical device. Local tolerance and systemic toxicity were followed prospectively. Only 2 patients developed s.c. injection site intolerance, and in both cases doses of 50 mg/ml or more were being administered. Most of the patients in this study were rotated to oxycodone because of opioid toxicity, and in 34% of those patients their delirium subsided. A subgroup of 19 patients who underwent rotation to oxycodone SC from morphine and hydromorphone were studied for equivalent analgesia with oxycodone. We found a ratio (mean +/- SD) of 1.2+/-0.4 for morphine s.c. to oxycodone s.c. and a mean ratio of 0.5+/-0.4 for hydromorphone s.c. to oxycodone s.c. When hydromorphone s.c. was converted to a morphine s.c. equivalent dose and the results for these patients were added to those for the morphine s.c. group, the mean and median overall ratios of morphine s.c. equivalent dose to oxycodone were 1.9+/-1.5 and 1.4, respectively. The cost of the oxycodone s.c. was also evaluated and was found to be comparable to that of morphine s.c. and lower than that of hydromorphone s.c. We conclude that s.c. oxycodone can be an effective, safe and inexpensive alternative opioid agonist.

Adult↗

Peptide binding alpha1alpha2 domain of HLA-B27 contributes to the disease pathogenesis in transgenic mice.

Human spondyloarthropathies are strongly associated with a major histocompatibility complex (MHC) class I allele, HLA-B27. HLA-B27 transgenic mice and rats demonstrate many features of these diseases further confirming the role of HLA-B27 in disease. Yet the exact role of this molecule in disease pathogenesis is not clearly understood. We have previously reported spontaneous arthritis and nail disease in HLA-B27 transgenic mice lacking beta2-microglobulin (B27+beta2m(o)). These observations along with binding studies of B27 derived peptides to HLA-B27 molecule itself led to two hypotheses: (i) HLA-B27 derived peptide as a source of autoantigen; and (ii) HLA-B27 functions as an antigen presenting molecule. In this report, we confirm spontaneous disease in transgenic mice expressing a hybrid B27 molecule with alpha1alpha2 domain of B27 and alpha3 domain of mouse H-2Kd. These mice developed spontaneous arthritis and nail disease when transferred from specific pathogen free barrier facility to the conventional area. Other control mice with MHC class I transgene (e.g., HLA-B7, HLA-Cw3, and H2-Dd) did not develop such disease. In a MHC reassembly assay, binding of similar peptides to both wild type and hybrid B27 molecules was observed. In addition, the hybrid B27 molecule lacks at least one of the 3 proposed peptides from the third hypervariable (HV3) region of HLA-B27. These data strongly suggest that HLA-B27 molecule is an antigen presenting molecule rather than a peptide donor in the disease pathogenesis.

Animals↗

A randomized controlled trial of local injections of hyaluronidase versus placebo in cancer patients receiving subcutaneous hydration.

BACKGROUND: Most cancer patients develop reduced oral intake or dehydration before death. Subcutaneous hydration (SCH) can be safe and effective. SCH is frequently administered using hyaluronidase to improve fluid absorption. The objective of this study was to determine the effects of hyaluronidase on patient comfort during bolus SCH. PATIENTS AND METHODS: Twenty-one cancer patients requiring parenteral hydration were administered a 500 cc bolus of two-thirds dextrose (5%) and one-third normal saline solution subcutaneously at 08:00 and 16:00 hours during day 1 and day 2. On day 1 patients were randomized on a double-blind basis to receive 150 units of hyaluronidase versus placebo as a bolus into the site of infusion immediately before starting each one-hour infusion. During day 2 patients were crossed over to receive the alternate treatment at a new infusion site. Visual analogue scales (0 = best, 100 = worst) for pain and swelling at the infusion site were completed by each patient. In addition, investigators blindly assessed the site of infusion for the presence of edema, rash, and leakage. RESULTS: No significant differences were observed for pain, swelling, edema, rash or leakage between the placebo and the hyaluronidase scores. After completion of the two days of the study, patients blindly chose hyaluronidase in 1 (5%) case, placebo in 5 (24%) cases, and no preference in 15 (71%) cases (P < 0.01). There was no treatment or interaction effect for pain, except for a period effect (P = 0.045) for the morning bolus administration. There were no treatment, period, or interaction effects for any of the other variables. CONCLUSIONS: Our results suggest that hyaluronidase is not necessary for routine bolus SCH. It may still be useful for a minority of patients who are not able to tolerate infusion well due to swelling or pain.

Cross-Over Studies↗

Prospective single blinded randomised controlled trial of two orally administered activated charcoal preparations.

OBJECTIVES: To compare two activated charcoal preparations (Carbomix and Actidose-Aqua) in terms of amount ingested and incidence of vomiting after ingestion. METHODS: Single blinded prospective randomised controlled trial. RESULTS: The mean amount of charcoal ingested was Carbomix 26.5 g, Actidose-Aqua 19.5 g. The mean difference was 7 g (95% confidence interval (CI) 1.5 to 12.4 g). The incidence of vomiting was for the Carbomix 6% and the Actidose-Aqua 8%. The mean difference in vomiting was 2% (95% CI -0.8 to 4.8) CONCLUSIONS: Carbomix administration results in an increased amount of activated charcoal ingested after oral administration. Rates of vomiting after activated charcoal administration were low when compared with previously reported rates.

Antidotes↗

A comparison of patient and proxy symptom assessments in advanced cancer patients.

The purpose of this study was to compare patient and proxy (physician and nurse) assessments of symptoms in advanced cancer patients. The sample consisted of 49 patients with advanced cancer admitted to an acute palliative care unit. Three independent assessments were completed for each patient on two occasions within 11 days of admission. On each occasion, symptoms were rated independently by the patient and two proxies (treating physician and nurse), using the Edmonton Symptom Assessment System (ESAS). The ESAS is a nine-item visual analogue scale (VAS) for assessing pain, activity, nausea, depression, anxiety, drowsiness, appetite, well-being and shortness of breath. Symptom ratings were compared using a repeated-measures ANOVA procedure and correlations. Average physician ratings were generally lower than average patient ratings for both occasions. Average nurse ratings agreed more closely with patient ratings, with a trend towards lower ratings on occasion 1 and higher ratings on occasion 2. There was a significant rater (person rating the effects) effect (P < 0.01) for three of the nine symptoms: physicians rated drowsiness, shortness of breath and pain significantly lower than patients. For drowsiness and shortness of breath, these differences were clinically relevant, representing a difference of more than 12 mm on a 100-mm VAS. The accuracy of assessments amongst those rating the symptoms did not improve over time. Proxy assessments of symptom intensity, particularly by physicians, were significantly lower than patient assessments for three of the nine symptoms. Further research regarding the reliability of patient and proxy assessments is needed to assess and manage symptoms in advanced cancer effectively.

Aged↗

Temporal distribution of deaths in cancer patients admitted to a palliative care unit.

The timing of death has received much attention, particularly in the area of sudden cardiac death. Many studies have demonstrated that sudden cardiac death and other sudden deaths follow a circadian pattern. Deaths have also been reported to vary around dates that are especially meaningful to patients and families. To test these reported observations in a cancer palliative care population, we reviewed the date and time of death of 626 consecutive patients admitted to the palliative care unit of a western Canadian hospital. All patients were adults with advanced metastatic or locally recurrent cancer. A circadian distribution in the time of deaths was observed; 225 deaths occurred between 20:00 and 06:00 (261 deaths expected) versus 401 deaths between 06:00 and 20:00 (365 deaths expected) (p = 0.0037). The distribution of deaths did not change significantly according to day of the week or month of the year. Based on patient birthday, 41 deaths occurred during the three weeks before a birthday (33.5 deaths expected) versus 26 deaths during the three weeks after a birthday (33.5 deaths expected) (p = 0.067). There appear to be fewer deaths during the evening and night; there does not appear to be a decline in deaths before the patient's birthday; and any temporal distribution of deaths in this population appears to be minimal.

Age Factors↗

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Dental Prophylaxis↗

Herpes simplex type 1 induction of persistent NF-kappa B nuclear translocation increases the efficiency of virus replication.

The latent form of the dimeric transcription factor NF-kappa B is sequestered in the cytoplasm by proteins containing ankyrin repeats, such as 1 kappa B alpha and beta, or by the p105 precursor form of the NF-kappa B p50 subunit. Tumor necrosis factor alpha or virus infection can cause targeted destruction of 1 kappa B and nuclear translocation of NF-kappa B. Following translocation, NF-kappa B mediates immune, inflammatory, or anti-apoptotic responses. Here we present evidence that beginning at around 6 h postinfection, herpes simplex virus (HSV) induces a persistent translocation of NF-kappa B into the nucleus of C33 cells, coincident with loss of both 1 kappa B alpha and 1 kappa B beta. Translocation failed to occur when infecting virus was preincubated with neutralizing antibody to viral envelope glycoproteins gD or gH, thus preventing entry, or when cells infected with viruses expressing mutated forms of immediate-early regulatory proteins lCP4 or lCP27. Surprisingly, no increase in the trans-activation function of NF-kappa B, as assayed by transient expression of CAT, was detected following HSV infection. The significance of NF-kappa B nuclear translocation for virus replication was demonstrated by an 80-90% reduction in virus yield following infection of C33 cells expressing a constitutive repressor form of 1 kappa B alpha. Models that reconcile nuclear translocation of NF-kappa B with the inability to detect NF-kappa B-dependent gene expression are discussed.

Biological Transport↗

Dose ratio between morphine and methadone in patients with cancer pain: a retrospective study.

BACKGROUND: Current equianalgesic reference tables, based largely on single dose studies, give dose ratios of 1:1 to 4:1 for oral morphine to oral methadone, which possibly are inaccurate in patients with cancer pain who are exposed to multiple doses of these opioids. The purpose of this study was to determine the equianalgesic dose ratio between morphine and methadone in patients with cancer pain and to establish whether the dose ratio changes as a function of previous opioid dose. METHODS: A retrospective analysis of consecutive rotations involving morphine and methadone using standard selection criteria identified a total of 20 evaluable rotations (14 from morphine to methadone and 6 from methadone to morphine). Opioid doses and pain intensity levels pre- and postrotation were analyzed. RESULTS: Median dose ratios (lower-upper quartiles) for morphine to methadone and methadone to morphine rotations were 11.36 (range, 5.98-16.27) and 8.25 (range, 4.37-11.3), respectively (P = 0.23). Combining all 20 rotations, a unified median dose ratio of 11.2 (range, 5.06-13.24) was calculated. There was no significant difference in pain intensity levels pre- and postrotation as recorded on a visual analogue scale. Univariate correlational analysis of dose ratio and the level of daily morphine dose prior to rotation revealed a Spearman correlation coefficient of 0.86 (P = 0.0001). In patients receiving >1165 mg per day prior to methadone rotation, a median dose ratio of 16.84 (range, 12.25-87.95) was observed, which was approximately 3 times higher compared with a median dose ratio of 5.42 (range, 2.95-9.09) (P = 0.007) for the 50% of patients receiving lower morphine doses. CONCLUSIONS: The results highlight the general underestimation of methadone potency and the consequent risk of potential life-threatening toxicity. The strongly positive correlation between dose ratio and previous morphine dose suggests the need for a highly individualized and cautious approach when rotating from morphine to methadone in patients with cancer pain.

Administration, Oral↗

Intervention with the hypoxic tumor cell sensitizer etanidazole in the combined modality treatment of limited stage small-cell lung cancer. A one-institution study.

PURPOSE: We report the toxicity, patterns of failure and survival of a cohort of patients with limited disease (LD) small-cell lung cancer (SCLC) treated with combined radiation and chemotherapy. During the course of thoracic irradiation, we added intravenous (i.v.) etanidazole (SR-2508, a third-generation 2-nitroimidazole) as a hypoxic cell sensitizer in an attempt to reduce the primary local failure rate and improve survival. METHODS AND MATERIALS: Between July 1988 and August 1990, 30 consecutive patients with limited disease SCLC were enrolled and treated on a Phase II protocol receiving a standard combination chemotherapy regimen utilizing i.v. cisplatin 25 mg/m2/day x 3 days, i.v. etoposide 100 mg/m2/day x 3 days alternating with intravenous cyclophosphamide 1000 mg/m2/day, intravenous doxorubicin 15 mg/m2, and intravenous vincristine 2 mg (CAV) to a total of six cycles every 3 weeks. Radiotherapy and etanidazole were started after the first cycle of chemotherapy. Etanidazole was administered intravenously at a dose of 2 g/m2 three times per week for a total of 30 g/m2 during the course of thoracic radiation that delivered 50.00 Gy tumor dose in 25 fractions in an overall time of 6 weeks. RESULTS: The overall response rate of the primary lesion in the thorax was 96% (CR + PR), with 64% complete responses. The median time to treatment failure was 18 months. Of the patients that have relapsed, only 18% failed in the thorax (alone or concomitant with other sites). This is a marked improvement compared to the 40-50% rate reported in the literature. The 2-year crude survival was 46%. The 3- and 5-year crude survival rate with no evidence of disease was 33 and 30%, respectively. We have observed a 10% increase in the incidence of transient etanidazole related peripheral neuropathies compared to previous etanidazole studies not utilizing systemic chemotherapy. There was no increased incidence of radiation esophagitis, pulmonary toxicity, or nephro- or myelotoxicity over and above what has been routinely observed with this radio/chemotherapy regimen. There were no treatment related deaths. CONCLUSION: The moderate increase in etanidazole-related transient peripheral neuropathies could have been related to the concomitant use of etanidazole with vincristine and cisplatin. Although the almost 50% improvement in the incidence of tumor failure rate in the thorax in this small group of patients did not correlate with an equal marked improvement in their survival, the 5-year survival outcome in our series is at least equal or better than the best reports in the literature of larger clinical trials. We believe there is sufficient data from this study, particularly the improvement of local tumor control, to warrant a large randomized controlled clinical trial, using the most current systemic chemotherapy with concomitant thoracic irradiation with or without the most effective available hypoxic cell cytotoxic/sensitizer.

Antineoplastic Combined Chemotherapy Protocols↗