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Biomedical subjects

P Murray

Publications and source records attributed to P Murray.

At least 19 recordsLinked to original sources

A randomized trial of intrahepatic infusion of fluorodeoxyuridine with dexamethasone versus fluorodeoxyuridine alone in the treatment of metastatic colorectal cancer.

To decrease the toxicity of hepatic arterial fluorodeoxyuridine (FUDR) administered through an Infusaid pump (Shiley Infusaid, Inc., Norwood, MA), 50 patients with liver metastases from colorectal cancer were selected randomly to receive FUDR, 0.3 mg/kg/d, for 14 of 28 days, with or without a total dose of 20 mg of hepatic arterial dexamethasone for 14 of 28 days. Patients were stratified according to the percentage of liver involvement by tumor and the perfusion pattern on macroaggrated albumin perfusion scan (MAA) scan. There was a trend toward decreased frequency of bilirubin levels in the group receiving dexamethasone plus FUDR versus the group receiving FUDR alone (9% and 30%, respectively, had a 200% or greater increase from baseline; P = 0.07). Patients in the group treated with dexamethasone and FUDR received higher doses of FUDR in the second, third, fifth, and sixth months than those receiving FUDR alone; however, this was statistically significant only in the fifth month (percentages of planned dose received: 42% and 19%, respectively; P = 0.05), and there was no overall difference for the total 6-month period. The complete and partial response rates were increased in patients receiving dexamethasone and FUDR versus FUDR alone (8% and 63% versus 4% and 36%, respectively; P = 0.03), and there was a trend toward increased survival with the addition of dexamethasone (median, 23 months and 15 months, respectively; P = 0.06). In conclusion, the use of hepatic arterial dexamethasone is associated with an increased response rate and a trend toward increased survival and decreased bilirubin levels. Therefore, the authors recommend additional investigation of the use of dexamethasone with chemotherapy to treat hepatic metastases.

Adult

Evaluation of microbiological processing of urine specimens: comparison of overnight versus two-day incubation.

In this study the value of urine culture incubation for 1 versus 2 days was determined. The results of the study indicate that 1 day of incubation is reliable if (i) all specimens are incubated for a full 24 h, (ii) all specimens with less than 10(4) uropathogens per ml are incubated for an additional day to ensure accurate quantitation, and (iii) specimens from patients with suspected funguria are incubated for a minimum of 2 days.

Bacteria

Prognostic value of quality-of-life scores during chemotherapy for advanced breast cancer. Australian New Zealand Breast Cancer Trials Group.

PURPOSE: We observed that quality-of-life (QL) scores, collected to evaluate treatment in a randomized trial in advanced breast cancer, predicted survival duration. This report explores the prognostic associations between QL and survival in more detail. PATIENTS AND METHODS: In a randomized clinical trial comparing intermittent and continuous therapy policies for patients with advanced breast cancer, QL was measured by linear analog self-assessment (LASA) and the Quality-of-Life Index (QLI). Baseline scores and subsequent changes were included in statistical models of survival duration, with and without other prognostic factors. RESULTS: Physician assessment of QLI and patient LASA scores for physical well-being (PWB), mood, nausea and vomiting, appetite, and overall QL (but not pain) at the commencement of treatment were significant predictors of subsequent survival. Scores for PWB and QLI were independent of other prognostic factors. Changes in scores were also prognostically important. Both baseline and change in scores for PWB, mood, pain, and QLI after the first three treatment cycles, but before an arbitrary 180-day time point, were significantly predictive of survival beyond that time. Both QLI and PWB were prognostically independent of tumor response. Although QL improvement was correlated with tumor response, continuous therapy yielded significantly better QL scores, even in nonresponders. CONCLUSION: These findings support the validity of the simple QL measures used in the trial. They are compatible with the simple explanation that patients perceive disease progression before it is clinically evident, but also with a causal relationship between QL and survival duration.

Breast Neoplasms

Interferon alfa-2a and fluorouracil in the treatment of patients with advanced esophageal cancer.

PURPOSE: The trial was undertaken to determine the response rate to and toxicities from the combination of interferon alfa-2a (IFN) and fluorouracil (FU) in patients with advanced esophageal cancer. MATERIALS AND METHODS: In this prospective phase II trial conducted at a large tertiary referral cancer center and university hospital, 40 patients with advanced locoregional, metastatic epidermoid, or adenocarcinoma of the esophagus were given FU 750 mg/m2 by 24-hour continuous intravenous infusion days 1 to 5, followed by weekly outpatient bolus FU 750 mg/m2 and IFN 9 x 10(6) U three times per week from day 1. Dose was attenuated for fatigue, neurotoxicity, gastrointestinal toxicity, and myelosuppression. RESULTS: Complete and partial responses were seen in 10 of 37 assessable patients with esophageal cancer (27%; 95% confidence interval, 0.13 to 0.41). Although substantial, toxicity was tolerable and primarily involved fatigue and mild myelosuppression. The median duration of response was 6.4 months (range, 2.8 to 14+ months). CONCLUSION: The combination of IFN and FU is an active regimen in the treatment of advanced esophageal cancer with a response rate similar to that reported for cisplatin-containing combinations in similar patient populations. Further studies based on this combination are indicated.

Adenocarcinoma

Lack of efficacy of high-dose leucovorin and fluorouracil in patients with advanced pancreatic adenocarcinoma.

Leucovorin potentiates the cytotoxicity of fluorouracil (5-FU) in experimental tumor systems and appears to enhance the effectiveness of 5-FU in patients with colon cancer. Twenty-two eligible patients (18 previously untreated) with advanced pancreatic adenocarcinoma were treated in a phase II trial of leucovorin 500 mg/m2/d for 6 days by continuous intravenous infusion with 5-FU 370 mg/m2/d by rapid intravenous injection on 5 consecutive days, beginning 24 hours after initiation of leucovorin infusion. Among the 20 assessable patients, there were no complete or partial regressions, although there was one minor response lasting 4 months. Three patients had stable disease for 5, 20, and 21 months, respectively. Median survival was 10 weeks. Toxicity was predominantly mucosal; stomatitis grade 2 or worse was seen in five patients, and diarrhea grade 2 or worse was seen in four. Hospitalization for toxicity was necessary in four previously untreated patients and three previously treated patients. The median WBC nadir was 4.6 (range, 1.4 to 9.6) x 10(3)/microL, and the median platelet nadir was 147.0 (range, 69.0 to 240.0) x 10(3)/microL. This combination of leucovorin and 5-FU did not demonstrate meaningful therapeutic activity in patients with adenocarcinoma of the pancreas and was associated with moderate to severe toxicity. It should not be considered a standard treatment for patients with this disease.

Adenocarcinoma

Epithelial cell type, clinical behaviour and AgNOR counts in thymic epithelial tumours.

The relationship between epithelial cell type, clinical behaviour and number of nucleolar organiser regions (AgNORs) was investigated in 37 thymomas and three thymic carcinomas. The thymomas were classified according to epithelial cell morphology as cortical (16 cases), medullary (8 cases) or mixed (13 cases). Seven cortical tumours had infiltrated the capsule or adjacent structures at the time of operation, whereas only one medullary and two mixed tumours showed evidence of invasion, the differences being statistically significant (P less than 0.01). None of the patients with medullary thymoma had myasthenia gravis, but there was a significantly higher incidence (P less than 0.001) among those with cortical or mixed tumours (six and three cases respectively). The mean AgNOR count for medullary tumours was 1.56, compared with 2.22 and 2.06 for cortical and mixed tumours. Although the counts for medullary tumours were significantly lower than for the other two types (P less than 0.01), there was considerable overlap. The mean count for the carcinomas was 4.94--significantly higher than for the thymomas (P less than 0.01)--but again overlap was considerable. No relationship was demonstrable between AgNOR counts, clinical stage, incidence of myasthenia or recurrence. It is concluded that although classification of thymomas based on epithelial cell type represents an improvement on previous classifications, it must be applied with caution. Similarly, AgNOR counts may give some indication of malignant potential, but their usefulness in individual cases is doubtful.

Adult

Interferon alpha-2a and 5-fluorouracil for advanced colorectal carcinoma. Assessment of activity and toxicity.

Preclinical data showed that the cytotoxic effects of 5-fluorouracil (5-FU) are augmented by interferon (IFN). In a small study, 13 of 17 patients with advanced colorectal cancer responded to a regimen of 5-FU with IFN. Using the same dose and schedule as in this pilot study, 38 previously untreated patients with metastatic colorectal carcinoma were treated with continuous intravenous (IV) infusion of 5-FU 750 mg/m2 daily for 5 days, followed by weekly bolus 5-FU at 750 mg/m2 and subcutaneous IFN at 9 million units three times per week. Of 35 evaluable patients, nine (26%) had a partial response (95% confidence limit, 11% to 41%), with a median response duration of 7.5 months (range, 4.4 to greater than 11.7 months). Seven patients (20%) had a minor response, and ten (28%) had stable disease. The most common toxicities observed were stomatitis (52%) and diarrhea (43%). Neurotoxicity was seen in 34% of patients and consisted of gait disturbance, dizziness, confusion, memory loss, and dementia. Because of toxicity, 84% of patients required a reduction of the IFN dose by at least 50%, and 63% required reduction of the 5-FU dose by at least 25%. Although the combination of 5-FU and IFN in patients with advanced colorectal carcinoma has some activity, the regimen was toxic, and the observed response rate (26%) was not substantially superior to alternative 5-FU programs.

Adult

The sensitivity of Neisseria gonorrhoeae, Chlamydia trachomatis, and herpes simplex type II to disinfection with povidone-iodine.

Povidone-iodine is an effective broad-spectrum disinfectant with no reported toxicity to the cornea and conjunctiva when applied topically in single dose to the ocular surface. We challenged four strains of Neisseria gonorrhoeae, a clinical isolate of Chlamydia trachomatis, and one strain of herpes simplex virus type II with three different concentrations of povidone-iodine (5%, 1%, and 0.1%) for one minute. The challenge inoculum of Neisseria gonorrhoeae and herpes simplex virus type II were completely sterilized by all three solutions. The chlamydia titer was reduced by two log units at the 5% and 1% concentrations, but not the 0.1% concentration. Povidone-iodine may be of potential use in the prophylaxis of newborns against ophthalmia neonatorum.

Blood

4-hydroxyandrostenedione--further clinical and extended endocrine observations.

4-Hydroxyandrostenedione (4-OHA) was administered (250 mg intramuscularly 2-weekly) in a phase 2 clinical trial to 20 postmenopausal patients with advanced breast cancer, who had failed other endocrine therapy. Seven out of 18 assessable patients (39%) responded with minimal toxicity. Endocrine studies demonstrated that the drug produced significant initial falls in oestradiol and oestrone levels, but that these levels rose toward pretreatment levels as the study progressed. Sex hormone binding globulin (SHBG) levels gradually fell during the study suggesting that the drug has a minor degree of androgenic activity albeit of no clinical significance. There was a transient reduction of adrenal steroid levels, which remained however within the normal range. There were no symptoms of adrenal insufficiency.

Aged

Development of reference and working spatial memory in preschool children.

Three groups of preschool children (aged 18 to 28, 33 to 42, and 47 to 58 months) were given a radial search test similar to the radial arm maze used with nonhuman subjects. The children searched for chocolate sweets among 10 labeled locations in a room, 5 of which were baited with a sweet. Older children outperformed the intermediate group, who in turn outperformed the youngest group in requiring fewer choices to retrieve all of the sweets. Working memory and reference memory aspects of performance were then separated: Reference memory (restriction of choices to the baited subset) in older children was superior to that in the youngest group but not to that in the intermediate group. In terms of working memory (avoidance of repeat responses to already visited locations), the older group made fewer errors than the intermediate group, who, in turn, made fewer errors than the youngest group. We concluded that working and reference components of spatial memory in children may share common elements, perhaps the ability to recognize places as familiar, although reference memory may develop earlier than working memory.

Attention

A longitudinal study of the contribution of dental experience to dental anxiety in children between 9 and 12 years of age.

Dental records of a group of children of both sexes were examined systematically over a period of 3 years to determine if the quantity and quality of their dental experience would be associated with increases in dental anxiety. The study was a follow-up of an earlier cross-sectional survey in which older children had demonstrated increases in dental anxiety with age. According to the evidence obtained from their dental records, the children were divided into four groups depending on their patterns of attendance (regular/irregular) and whether or not they had received invasive treatment. The results indicated that children who did not receive invasive treatment during the period under scrutiny were significantly more anxious than those who had. On the other hand, the dental anxiety of children who attended regularly and received invasive treatment did not change significantly. This applied to boys and girls alike.

Age Factors

Acetabular cup-siting device for total hip arthroplasty.

A method for improving acetabular cup positioning at arthroplasty is introduced. The anatomic and engineering principles involved are explained. The device used for this method of siting is described. The method was tested in cadaver experiments and resulted in a 380% improvement of anteversion-retroversion position and a 370% improvement in abduction position over conventional siting. The value of this method in conventional and revision arthroplasty is suggested.

Cadaver

Effect of rotary electric toothbrush versus manual toothbrush on periodontal status during orthodontic treatment.

Adolescents with fixed orthodontic appliances frequently have increased levels of plaque accumulation and gingivitis. The purpose of this study was to determine whether a rotary electric toothbrush would be more effective than conventional toothbrushing in maintaining periodontal health in these patients. Forty adolescent patients were divided into equal groups matched for sex and age. Before and during placement of orthodontic appliances, one group was instructed in use of the rotary electric toothbrush and the other in the use of a conventional toothbrush; these instructions were reinforced at monthly visits thereafter. Baseline clinical assessments of Plaque Index, Gingival Index, and bleeding tendency were made on six standard teeth before appliances were placed. assessments were repeated at 1, 3, 6, 9, 12, and 18 months after appliances were placed. Intragroup and intergroup differences were tested by a two-way analysis of variance. At baseline there were no significant differences between the two groups for any study variable. During the 18-month study period, however, plaque accumulation and gingivitis increased significantly over baseline levels in the control group (p less than 0.01) but remained stable in the group using the rotary electric toothbrush. In addition, the control group showed significantly greater plaque (p less than 0.01), gingival inflammation (p less than 0.001), and gingival bleeding on probing (p less than 0.001) than did the treatment group from the 1- to 18-month examinations. These data suggest that the rotary electric toothbrush is more effective than conventional toothbrushes for removing plaque and controlling gingivitis in adolescents during orthodontic treatment with fixed appliances.

Child

Standardization of disk diffusion and agar dilution susceptibility tests for Neisseria gonorrhoeae: interpretive criteria and quality control guidelines for ceftriaxone, penicillin, spectinomycin, and tetracycline.

A six-laboratory study developed a standardized method for determining the susceptibilities of Neisseria gonorrhoeae strains to penicillin, tetracycline, spectinomycin, and ceftriaxone. Three quality control organisms were also selected, and quality assurance guidelines were initially generated for the disk diffusion and agar dilution methods. The medium recommended for gonococcal susceptibility testing was GC agar with a defined "XV-like" supplement. The supplement should be free of cysteine, a component implicated in the inactivation of some newer beta-lactam compounds. Penicillin, tetracycline, spectinomycin, and ceftriaxone were stable in agar plates stored at 3 to 5 degrees C for at least 2 weeks. Numerous GC agar and drug disk lots were used during the trials without significant variation in test results. Several other gonococcal strains were recommended for additional medium quality assurance. The disk quality control zone limits were established for N. gonorrhoeae ATCC 49226 (formerly CDC F-18) and Staphylococcus aureus ATCC 25923. MIC quality control ranges were also developed for N. gonorrhoeae ATCC 49226 and S. aureus ATCC 29213. The interpretive criteria for penicillin were as follows: susceptibility, greater than or equal to 47 mm (diameter of inhibition zone) (less than or equal to 0.06 micrograms/ml [MIC]); resistance, less than or equal to 26 mm (greater than or equal to 2 micrograms/ml). For tetracycline they were as follows: susceptibility, greater than or equal to 38 mm (less than or equal to 0.25 microgram/ml); resistance, less than or equal to 30 mm (greater than or equal to 2 micrograms/ml). For spectinomycin they were as follows: susceptibility, >/= 18 mm (</= 32 micrograms/ml); resistance, </= 14 mm (>/= 128 micrograms/ml). For ceftriaxone susceptibility, the criterion was >/= 35 mm (</= 0.25 micrograms/ml) with no other category. Criteria of </= 19 mm for plasmid-mediated resistances to penicillin and tetracycline were also confirmed. The false-susceptibility errors were </= 1% with these criteria.

Ceftriaxone

Effect on periodontal status of rotary electric toothbrushes vs. manual toothbrushes during periodontal maintenance. I. Clinical results.

The purpose of this study was to compare the Rotadent rotary electric toothbrush with conventional toothbrushing for its effectiveness in controlling supragingival plaque and gingival inflammation in periodontal maintenance patients. Forty subjects who had received periodontal treatment, including periodontal surgery, for moderate to advanced periodontitis and were on a 3-month periodontal maintenance were divided into two equal groups matched for age and sex. One group used conventional toothbrushing, dental floss, and toothpicks and the other used only the rotary electric toothbrush for a 12-month study period. Single-blind clinical assessments (Plaque Index, Gingival Index, bleeding tendency, pocket depth, and loss of attachment) were made at baseline and at 3, 6, 9, and 12 months after baseline. Subgingival debridement was performed 1 week after the baseline assessment and the 6- and 12-month examinations. Plaque removal was reinforced at 3-month intervals. Both groups had significantly improved scores (P less than 0.01) for Gingival Index and bleeding tendency during the 12-month period, but no differences were found between the groups at any examination. These results indicate that the rotary electric toothbrush is as effective for plaque removal and control of gingival inflammation as a combination of conventional toothbrushing, flossing, and toothpicks for patients in periodontal maintenance.

Adult