Improved diagnostic decision-making in pathology: do inference networks hold the key?
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Bayes Theorem↗
Biomedical subjects
N Anderson
Publications and source records attributed to N Anderson.
Overexpression of the tumour suppressor gene p53 is not implicated in neuroendocrine tumour carcinogenesis.
The tumorigenesis of neuroendocrine tumours remains poorly understood, although a minority, the familial multiple endocrine neoplasia (MEN 1 and MEN 2), are known to be of uncommon genetic origin. Mutation of the tumour suppressor gene, p53, is now known to be a common genetic alteration in about half of all types of non-endocrine cancers. In the present study, immunocytochemistry using the monoclonal anti-p53 antibody, DO-7, has been employed to investigate the accumulation of p53 immunoreactivity in a wide range of primary neuroendocrine tumours. Tumours (n = 109) were fixed and processed to paraffin wax according to a constant protocol. Sections were subjected to microwave antigen retrieval prior to immunostaining for p53. Positive nuclear immunostaining was observed in one medullary carcinoma of the thyroid (MCT), one lung carcinoid, and five small cell carcinomas of the lung (SCCL). All other tumour samples were consistently negative. As the neoplasia investigated in this study comprised a wide spectrum of neuroendocrine tumour types and ranged from minute, relatively benign lesions to malignant metastasizing disease and as there was no relationship between the presence of p53 overexpression and clinico-pathological features, the present study suggests that p53 gene mutation may be relatively unimportant in the genesis of neuroendocrine tumours.
Antibodies, Monoclonal↗
Ulnar club-hand and constriction-ring syndrome.
An infant presented with ulnar club hand and constriction ring syndrome involving all four limbs. The former abnormality was diagnosed by ultrasound at 23 weeks gestation. This association has not been previously described.
Abnormalities, Multiple↗
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↗
Predicting the severity of haemolytic disease of the newborn: an assessment of the clinical usefulness of the chemiluminescence test.
The ability of the chemiluminescence test (CLT) to predict the severity of haemolytic disease of the newborn (HDN) was determined in 80 alloimmunized pregnant women who delivered antigen-positive babies. In 54 cases of alloimmunization to D, results from the CLT showed better correlation with fetal outcome than anti-D concentration measured by AutoAnalyzer (r = 0.70 and 0.36 respectively). Results from the CLT permitted a threshold level of antibody activity (30%) below which 15/20 babies were unaffected or had mild disease, and only one required transfusion therapy in utero. CLT results above 30% were associated with moderate or severe disease in all cases. Results from the AutoAnalyzer proved a less reliable predictor of disease severity; three women with anti-D levels > 20 iu/ml delivered unaffected babies, and two women with anti-D levels < 10 iu/ml delivered babies who had required transfusion in utero. The clinical usefulness of the CLT derives from the possibility of avoiding invasive monitoring procedures in women with high levels of anti-D which is relatively non-functional.
Erythroblastosis, Fetal↗
Diarrhoea due to trichostrongylid larvae in Merino sheep--repeatability and differences between bloodlines.
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Animals↗
Production losses in Merino ewes and financial penalties caused by trichostrongylid infections during winter and spring.
The productivity of Merino ewes treated with ivermectin and a controlled-release capsule containing albendazole was compared with untreated ewes grazing the same pastures on each of 3 farms. Treated breeding ewes had significantly increased greasy fleece weights (GFW, 6.5% and 7.1%) compared with untreated breeding ewes, on 2 of 3 farms but treatment caused no significant increase in the GFW of non-breeding ewes. Other benefits of treatment on all farms were a significant increase in body weight gain (from 1.7 to 3.7 kg) and a significant decrease in the weight of dag removed at crutching (from 42 to 622 g). These benefits occurred despite the presence on each farm of worms resistant to benzimidazoles. One disadvantage of treatment was an increase in mean fibre diameter of wool from treated ewes of from 0.12 to 0.41 microns. This increase reduces the value of the wool. Partial budgets indicated a net loss of from 8 to 62 cents per ewe for treatment. However, potential benefits such as increased growth rate and wool production from lambs of treated ewes were not included in the analysis. On one farm ewes were classified as 'susceptible' to severe dag if they had a dag score > or = 4 at the time of capsule treatment. Ewes classified as 'susceptible' were about 7 times more likely to develop severe dag than were other ewes. There was no significant difference between the GFW of untreated 'susceptible' ewes and untreated ewes not classified as 'susceptible'.(ABSTRACT TRUNCATED AT 250 WORDS)
Albendazole↗
Oral ondansetron for the control of cisplatin-induced delayed emesis: a large, multicenter, double-blind, randomized comparative trial of ondansetron versus placebo.
PURPOSE: To investigate the efficacy and safety of oral ondansetron in the control of cisplatin-induced delayed emesis in patients who do not require rescue antiemetic therapy for acute emesis. PATIENTS AND METHODS: Five hundred thirty-eight chemotherapy-naive patients who received cisplatin chemotherapy (> or = 70 mg/m2), and who were not rescued for acute emesis, were eligible to be randomized to receive one of the three oral regimens to control delayed emesis. Group I received placebo on days 2 to 6; group II received ondansetron 8 mg twice daily on days 2 and 3 and placebo on days 4 to 6; group III received ondansetron 8 mg twice daily on days 2 to 6. All patients received intravenous ondansetron (0.15 mg/kg every 4 hours for three doses) for the control of acute emesis on day 1. The number of emetic episodes on days 2 and 3 combined (days 2/3, when incidence and severity of delayed emesis were expected to be greatest) was considered the primary measure of efficacy. RESULTS: Patients who received odansetron had significantly fewer emetic episodes on days 2/3, 4, and 5 than those who received placebo (P < or = .002 on each day). Additionally, significantly more patients who received ondansetron had a complete plus major response (C+MR; < or = two two emetic episodes) than those who received placebo on days 2/3 (56% v 37%, P = .001), 4 (94% v 85%, P = .005), and 5 (98% v 88%, P = .006). Patients who received ondansetron had significantly less nausea on day 2/3 when day-1 nausea was used as the baseline score (P = .025). Patients who received ondansetron also had significantly less nausea on day 4 (P = .042) and the results approached significance on day 5 (P = .066). CONCLUSION: Oral ondansetron had a significant effect in the control of cisplatin-induced delayed emesis and nausea in patients who had not required rescue antiemetics during the acute emesis period. The control of delayed nausea and vomiting was most notable in the immediate 2 days following cisplatin administration, with the clinical difference narrowing between the two treatment arms on subsequent days.
Administration, Oral↗
Detection of obstructive uropathy in the fetus: predictive value of sonographic measurements of renal pelvic diameter at various gestational ages.
OBJECTIVE: The goal of our study was to analyze the fetal renal pelvic diameters measured sonographically at several gestational intervals in live-born neonates subsequently found to have either obstructive uropathy or normal kidneys. This information will improve the efficacy of sonography in the diagnosis of obstructive uropathy. SUBJECTS AND METHODS: From an ongoing prospective study assessing the significance of fetal renal pelvic diameters of 4 mm or more at obstetric sonography, the findings in 29 obstructed kidneys in 24 babies were compared with the findings in 380 kidneys from 233 infants who had no obstruction. Twenty-three infants had unilateral obstruction of the ureteropelvic junction, two had unilateral renal obstruction at the ureterovesical junction, one had posterior urethral valves and in addition had both kidneys obstructed because of obstruction at the ureterovesical junction, one kidney was obstructed because of megaloureter, and one kidney was obstructed because of obstruction in a duplex collecting system. Obstruction was identified on nephrostograms, excretory urograms, or radionuclide renograms. The sonographic findings were compared at three gestational age ranges: 16-23 weeks' gestation, 24-30 weeks' gestation, and 31-40 weeks' gestation. The progression of pelvic dilatation in both groups (12 obstructed and 86 unobstructed) was analyzed for the subset of kidneys examined in all three time periods. RESULTS: At 16-23 weeks' gestation, the difference in mean pelvic diameter between obstructed and unobstructed kidneys was not statistically significant, but the difference between obstructed and unobstructed groups at 24-30 weeks' and 31-40 weeks' gestation was significant (p < .001). Renal pelvic diameter showed a much greater rise in diameter through pregnancy in the obstructed group than in the unobstructed group (p < .0003). The sensitivity of the cutoff point of 4-mm renal pelvic diameter for detecting obstruction was 76% before 23 weeks' gestation, including kidneys with a marked decrease in function postnatally; the sensitivity of a 10-mm cutoff point at 16-23 weeks' gestation was 12%. The likelihood that a fetus had renal obstruction increased with increasing diameter of the fetal renal pelvis in all three time periods. CONCLUSION: Kidneys with significant obstruction postnatally may have no dilatation of the renal pelvis before 23 weeks' gestation. Most obstructed kidneys had pelvic diameters of less than 10 mm before 23 weeks' gestation. During pregnancy, renal pelvic diameter increases at a greater rate in kidneys that later are shown to be obstructed than in those that are not obstructed.
Female↗
Prenatal sonography for the detection of fetal anomalies: results of a prospective study and comparison with prior series.
OBJECTIVE: Reported rates of sonographic detection of fetal anomaly vary widely. The purpose of our study was to determine how well we were detecting fetal anomaly in our region and to compare our results with published series using standardized criteria. SUBJECTS AND METHODS: Over a 2-year period, we compared the reports of sonographic studies done in 7880 pregnancies at 16-20 weeks' gestation with all pregnancy outcomes established by medical records and pathologic results of the infants, whether born alive or dead. Fetal anomaly was defined as any structural anomaly except for those specifically excluded. We compared our results, expressed as percentage of anomalies found and anomalies found per 1000 pregnancies screened, with those of published studies, modifying published figures where necessary to compensate for our defined exclusion criteria. RESULTS: At postnatal examination, we found 157 anomalies in 144 babies who had prenatal sonography at 16-20 weeks' gestation. We detected 93 anomalies (60%) in 84 fetuses, leading to termination of pregnancy in 42 cases (50% of anomalous fetuses). The prevalence of fetal anomaly in our population was 19.8 anomalies per 1000 pregnancies screened. We detected 11.8 anomalies per 1000 screened, leading to termination of 5.3 pregnancies per 1000 screened. Our success rate for fetal anomaly detection ranged from 92% for CNS anomalies to 31% for cardiac anomalies and 25% for craniofacial anomalies. There were fewer babies born with a major malformation in the group whose anomalies were detected prenatally (21%) than in the group whose anomalies were not detected (58%). By comparison, in prior series, prevalence of anomalies varied from 5.67 to 25.95 per-11000 screened; anomaly detection varied from 16.6% to 74.4%; detection rate varied from 3.08 to 11.03 per 1000 screened. There was no correlation between the percentage and per 1000 detection rates. Thus, the RADIUS and Helsinki trials had similar detection rates per 1000, but more than a twofold difference in percentage detection rate. Similarly, the percentage success rate in studies could be the same, but the detection rate per 1000 different threshold. There was a similar lack of correlation for rates of pregnancy termination. All series except for the RADIUS study reported a reduction in the rate of adverse outcome if the anomalies were detected prenatally. CONCLUSION: Our rate of detection of fetal anomaly is satisfactory for most organ systems but remains poor for cardiac, skeletal, and craniofacial anomalies. The relative ranking of the success of fetal anomaly detection in prior studies depends on whether the detection rate is reported as a percentage or as the number of anomalies detected per 1000 screened. Our results compare favorably with those reported in other series.
Congenital Abnormalities↗
Infusional cancer chemotherapy: historical evolution and future development at the Cancer Center of Boston.
Clinical studies of infusional chemotherapy at The Cancer Center of Boston began in 1980 at the New England Deaconess Hospital and from 1986 to the present have continued under the auspices of a network of free-standing ambulatory cancer treatment centers in Massachusetts. Over 50 peer-reviewed articles on infusional chemotherapy and 3 textbooks on the topic have been published by clinical investigators associated with The Center, including phase I, II, and III trials, multidrug infusion programs, and combined chemo/radiotherapy programs. Bringing together the total experience in this review provides a perspective to address those areas that have been inadequately explored and a framework for future development in the field. This paper represents a comprehensive synthesis and analysis of clinical infusional studies carried out at The Center to the present with the goal of achieving those objectives.
Ambulatory Care Facilities↗
Clinical applications of Bayesian belief networks in pathology.
Bayesian belief networks (BBNs) are a novel tool for representing knowledge about diagnostic decision making and for obtaining a numerical measure of certainty in the final diagnosis. Belief networks have been applied to the pathological assessment of breast, prostate and skin lesions and have been shown to provide consistency in the grading of microscopic features and improve diagnosis. These applications are reviewed in the current paper. The application of BBNs has been further facilitated through the use of standardised imagery which is stored digitally and used to enter evidence into a BBN. It is predicted that the further development of BBNs with improved logical capabilities represent the key to improved decision making in pathology.
Bayes Theorem↗
Chronic fatigue syndrome. ...and study them separately.
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Fatigue Syndrome, Chronic↗
Hydrochloric acid denaturation of colorectal tumour tissue infiltrated with bromodeoxyuridine.
The thymidine analogue, bromodeoxyuridine, is substituted into DNA during DNA synthesis and can be used to identify those cells which have passed through the S-phase of the cell cycle. Incorporated bromodeoxyuridine can be detected using anti-bromodeoxyuridine monoclonal antibodies which bind to the exposed bromodeoxyuridine in single-stranded DNA after a suitable denaturation step. Hydrochloric acid is the most commonly employed denaturation agent in bromodeoxyuridine monoclonal antibody methodologies. This preliminary study was to validate the hydrochloric acid denaturation step for colorectal tumour tissue infiltrated in vivo with bromodeoxyuridine. Standard immunohistochemistry and flow cytometric techniques using Bu20a were employed across a range of hydrochloric acid concentrations. Although high labelling indices were achieved using acid concentrations of 0.10 M HCl, the optimal hydrochloric acid concentration was not the same in all tumours. Sensitivity of DNA to hydrochloric acid denaturation should be carefully considered in bromodeoxyuridine methodologies using the monoclonal antibody Bu20a.
Antibodies, Monoclonal↗
Safe blood? HTLV-1 infection is crippling.
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Blood Transfusion↗
Successful resuscitation of a severely hypothermic neonate.
A profoundly hypothermic 5-hour-old infant in cardiac arrest was brought to the emergency department by paramedics. The infant was found wrapped in a garbage bag inside a freezer. She had been in the freezer for approximately four hours. Her initial rectal temperature was 16.2 degrees C. Active external and core warming modalities, including warm blanket, radiant heat lamp, warm humidified air, heated gastric lavage, and heated bladder lavage, were used to rewarm the infant. Her temperature rose to 30.5 degrees C in three hours (4.8 degrees C/hr). The infant converted from a slow idioventricular rhythm to sinus bradycardia at 49 minutes (20.4 degrees C) into the resuscitation. At 53 minutes (21.5 degrees C), the infant moved both upper extremities. At the time of discharge from the hospital, she had no significant physical or neurologic problems. Neurologic examination at 4 months was normal. This report supports prior recommendations to aggressively rewarm severely hypothermic infants in cardiac arrest.
Cardiopulmonary Resuscitation↗
Intake of trichostrongylid larvae by goats and sheep grazing together.
Cashmere goats and Merino sheep were grazed together at 7.5 animals per ha on annual rye grass and clover pasture in southern Victoria, a winter rainfall area. Intake of parasitic larvae was measured in oesophageal extrusa samples collected from 2 animals of each species, 4 times in one week, on 7 occasions between mid-March (autumn) and mid-June (winter). Pasture contamination with larvae was measured at the same times. The number of larvae per kg of green grass was lower than on green clover; the most heavily contaminated portion of the pasture was the mat of dead herbage on the ground. The diet selected by goats contained more green grass and dead herbage and less clover that that of sheep (P < 0.01). Goats ingested 643 infective trichostrongylid larvae per kg dry matter intake (DMI) versus 274 per kg DMI for sheep in autumn, increasing to 1892 versus 1143 in early winter. The heavier trichostrongylid burdens of goats compared with sheep, when grazed together, are due in part to greater rates of infection consequent on different grazing patterns as well as greater susceptibility to infection.
Animal Feed↗
Diarrhoea in merino ewes during winter: association with trichostrongylid larvae.
A study on 3 farms, each having a preventive strategy for the control of nematode infections, determined the risk factors associated with diarrhoea among Merino ewes in winter. Comparisons were made among groups of mated and unmated ewes with and without treatment with controlled-release capsules containing albendazole. Diarrhoea was assessed from the accumulations of faeces around the breech (dag score) and related to worm egg counts, total worm counts and histopathological findings. The overall prevalence of severe dag in ewes not treated with a capsule was 26% (221/844). In comparison, only 2.7% of treated ewes had severe dag. The adjusted odds ratio on each farm indicated that untreated ewes were between 12 and 16 times more likely to be affected with severe dag than ewes treated with a capsule. The effect of lactation was significant on only one farm whereas initial body weight had no significant effect. There was no significant association between worm egg counts and the occurrence of severe dag. There were significantly more eosinophils in the small intestine of ewes affected with severe dag compared with unaffected ewes. There were no significant differences in mast cell and globule leucocyte numbers between affected and unaffected ewes. This study provides strong evidence that the main cause of diarrhoea among Merino ewes grazing winter and early spring pastures is the ingestion of trichostrongylid larvae even by sheep that have a well-developed protective immune response to these parasites. New strategies for the control of nematode infections are needed to prevent diarrhoea and dag formation in adult sheep.
Animals↗