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Biomedical subjects

N Anderson

Publications and source records attributed to N Anderson.

At least 109 records · Page 6Linked to original sources

Expert system support using Bayesian belief networks in the diagnosis of fine needle aspiration biopsy specimens of the breast.

AIM: To develop an expert system model for the diagnosis of fine needle aspiration cytology (FNAC) of the breast. METHODS: Knowledge and uncertainty were represented in the form of a Bayesian belief network which permitted the combination of diagnostic evidence in a cumulative manner and provided a final probability for the possible diagnostic outcomes. The network comprised 10 cytological features (evidence nodes), each independently linked to the diagnosis (decision node) by a conditional probability matrix. The system was designed to be interactive in that the cytopathologist entered evidence into the network in the form of likelihood ratios for the outcomes at each evidence node. RESULTS: The efficiency of the network was tested on a series of 40 breast FNAC specimens. The highest diagnostic probability provided by the network agreed with the cytopathologists' diagnosis in 100% of cases for the assessment of discrete, benign, and malignant aspirates. Atypical probably benign cases were given probabilities in favour of a benign diagnosis. Suspicious cases tended to have similar probabilities for both diagnostic outcomes and so, correctly, could not be assigned as benign or malignant. A closer examination of cumulative belief graphs for the diagnostic sequence of each case provided insight into the diagnostic process, and quantitative data which improved the identification of suspicious cases. CONCLUSION: The further development of such a system will have three important roles in breast cytodiagnosis: (1) to aid the cytologist in making a more consistent and objective diagnosis; (2) to provide a teaching tool on breast cytological diagnosis for the non-expert; and (3) it is the first stage in the development of a system capable of automated diagnosis through the use of expert system machine vision.

Bayes Theorem↗

Diagnosis of intraventricular hemorrhage in the newborn: value of sonography via the posterior fontanelle.

OBJECTIVE: Intraventricular hemorrhage in neonates with normally sized ventricles is overlooked when sonograms obtained via the anterior fontanelle fail to show a small amount of blood in the occipital horns of the lateral ventricle. Because visualization of the occipital horns is improved when sonograms are obtained via the posterior fontanelle, we studied the efficacy of posterior fontanelle sonography in establishing the diagnosis of intraventricular hemorrhage for 259 neonates. MATERIALS AND METHODS: We compared cranial sonograms obtained via both the anterior and the posterior fontanelles for 34 infants who had intraventricular hemorrhage and whose mean age at birth was 28 weeks (range, 23-40 weeks) with sonograms for 225 neonates who did not have hemorrhage and whose mean age at birth was 31 weeks (range, 24-42 weeks). Sonograms were assessed for satisfactory visualization of the occipital horns of the lateral ventricles, for the characteristics of intraventricular hemorrhage, if present, and for ventricular size, assessed as normal or showing mild, moderate, or marked dilatation. The technique of posterior fontanelle sonography involves obtaining parasagittal views of the occipital horns of the lateral ventricles and coronal scans of the occipital horns at the level of the calcarine fissure. The data from the contrasting groups of neonates were analyzed with Student's t-test or 2 x 2 tables as appropriate. Five autopsies were done; two confirmed intraventricular hemorrhage, and three confirmed the absence of intraventricular hemorrhage. RESULTS: Sonograms obtained via the posterior fontanelle were satisfactory for 92% of neonates born at less than 32 weeks' gestation and 88% of all neonates scanned. The mean age at birth of those with satisfactory sonograms obtained via the posterior fontanelle was 29 weeks (SD, 4 weeks); in comparison, a mean age at birth of 35 weeks (SD, 5 weeks) was associated with unsatisfactory sonograms (p < .0001). Intraventricular hemorrhage was detected via the posterior fontanelle but not via the anterior fontanelle on the initial diagnostic scan for 14 neonates. The ventricles were more likely to be normally sized when intraventricular hemorrhage was seen via the posterior fontanelle only (86%) than when intraventricular hemorrhage was seen via the anterior fontanelle as well (50%) (Fisher's exact test; p = .04). CONCLUSION: Our results show that sonograms obtained via the posterior fontanelle increase the rate of detection of intraventricular hemorrhage in neonates with normally sized ventricles.

Cerebral Hemorrhage↗

Jass' classification revisited.

BACKGROUND: In 1986, Jass and colleagues claimed to have improved on Dukes' classification of prognosis for carcinoma of the colon and rectum. To have clinical relevance, such results should be reproducible and confirmed by other institutions. STUDY DESIGN: Retrospective clinicopathologic study of 312 carcinomas of the colon and rectum to determine whether or not Jass' classification is superior to that of Dukes' as assessed by their relative reproducibility and prognostic significance. RESULTS: Dukes' classification had excellent intraobserver and interobserver reproducibility (kappa values of 0.86 and 0.93, respectively). In contrast, the reproducibility of variables assessed by Jass showed only slight to fair agreement (lymphocytic infiltration: intraobserver and interobserver kappa values of 0.08 and 0.05, respectively, growth pattern: intraobserver and interobserver kappa values of 0.37 and 0.41, respectively). Dukes' stage and patient age were the most important prognostic variables on multivariate regression analysis. Tumor differentiation, nuclear polarity, tubule configuration, and lymphocytic infiltration remained significantly related to survival in the presence of Dukes' stage and age. The model which best predicted prognosis was a combination of Dukes' stage, patient age and tumor differentiation. Further addition of the variables assessed by Jass to this model did not significantly improve the prediction of prognosis. CONCLUSIONS: Dukes' classification is of greater prognostic value and more reproducible than the components of Jass' classification. The continued use of Dukes' classification is, therefore, warranted for prognostic and therapeutic decisions in patients with carcinoma of the colon and rectum.

Colonic Neoplasms↗

Cancer chemotherapy and infusional scheduling.

The practice of infusional cancer chemotherapy has evolved over the past decade as our increased understanding of tumor cell kinetics and drug pharmacology has brought into focus the concentration x time formulation and its importance in tumor cell killing and host tolerance. Technologic advances have contributed substantially to the practical capability of infusional drug delivery, with improved vascular access and ambulatory infusion pumps. In the past 10 years, infusional schedules have been used for virtually every class of antineoplastic agent and have demonstrated an improved therapeutic index by reduced or altered toxicity (doxorubicin, fluorouracil, ifosfamide, platinum analogs) or increased tumor cell killing (fluorouracil, etoposide, cladribine). Although there are few phase III trials comparing infusion and bolus administration, the evidence is clear that toxicity is altered and therapeutic benefit is not diminished by infusional schedules of drug administration.

Antineoplastic Agents↗

Fire fighting.

Explore the source record for details and available documents.

Health Services Research↗

Recent advances in the treatment of advanced colorectal cancer.

The treatment of advanced colorectal cancer has improved in recent years. Prospective randomized trials comparing innovative therapies with the "standard" bolus dose of 5-fluorouracil (5-FU) found increased response rates after biochemical modification of the drug, infusion administration of 5-FU, and direct intrahepatic arterial infusion. Although the impact on survival of these techniques has been minimal, it is possible that these innovative approaches provide an incremental survival advantage for certain subgroups of patients that may be the foundation for additional therapeutic improvements in the future.

Antineoplastic Combined Chemotherapy Protocols↗

Prenatal diagnosis of colon atresia.

We report a case of colon atresia diagnosed pre-natally at 32 weeks' gestation. The fetal transverse colon was dilated. Complete atresia of the middle transverse colon was confirmed after birth. Small bowel dilatation (and clinical obstruction) did not develop until after 24 h of age.

Adult↗

Prenatal diagnosis of unilateral hydrocephalus.

We report a case of unilateral hydrocephalus diagnosed at 20 weeks' gestation, at which time marked facial and cranial asymmetry was present already. Brain mantle reconstitution was incomplete following ventriculo-peritoneal shunting, and the child has significant neurodevelopmental disability.

Adult↗

Treatment and control of the intestinal fluke, Skrjabinotrema ovis.

The small intestinal fluke, Skrjabinotrema ovis, is common among sheep in the Xinjiang region of western China. Up to 65,000 flukes per sheep were found during September when sheep were grazing summer pastures at high altitudes. Efficacy studies of some common flukicides revealed that oxyclosanide and triclabendazole were not effective in reducing the egg output of S. ovis, whereas closantel and praziquantel reduced egg counts by up to 98%. Praziquantel at 25 and 50 mg kg-1 reduced worm counts by 99%. Albendazole at 15 mg kg-1 reduced egg counts by 83% and worm counts by 91% but at lower dose rates it was ineffective.

Albendazole↗

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↗

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↗

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↗

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↗

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↗

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↗

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↗

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↗