Biomedical subjects
Publications and source records attributed to J A Spencer.
Endometrial cancer is the second most common gynaecological malignancy. The usual presentation with post-menopausal bleeding results in an early diagnosis in most cases and thus there is opportunity for cure. Magnetic resonance (MR) imaging is pivotal in the decision-making process regarding treatment options. We present a review of the magnetic resonance (MR) findings to illustrate its role in the staging of endometrial cancer.
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A survey of the multi-stable isotopic composition of an active pharmaceutical ingredient (API), naproxen, was performed to assess the potential of Isotope Ratio Mass Spectrometry (IRMS) to distinguish the provenance of APIs. Twenty-six lots of naproxen from six manufacturers representing four countries (Italy, India, Ireland, and the USA) were analyzed for three isotope ratios (13C/12C, 18O/16O, and D/H). The samples were analyzed by either Elemental Analyzer/Isotope Ratio Mass Spectrometry (EA/IRMS: carbon (delta13C)) or by Thermal Conversion-EA/IRMS (TCEA/IRMS: hydrogen (deltaD) and oxygen (delta18O)). Bivariate and trivariate isotope ratio graphs for naproxen show marked clustering of the data for five out of the six naproxen manufacturers, suggesting that IRMS may be a plausible means to screen for manufacturer of given APIs.
PURPOSE: We assessed the potential of magnetic resonance urography (MRU) in the evaluation of hydronephrosis not explained by standard investigation in patients at high risk for upper tract urothelial cancer. MATERIALS AND METHODS: A total of 23 consecutive patients in a specialist urological unit with unexplained hydronephrosis prospectively underwent MRU which comprised overview heavily T2-weighted MR urographic images followed by focused high resolution turbo spin echo T2-weighted sequences obtained in an axial and coronal oblique plane through the level of urinary obstruction. All were at high risk for urothelial cancer and had either contraindications to or problems with standard investigations including poor contrast excretion due to obstruction or renal failure, failed ureteral cannulation or contrast allergy. Clinical events and imaging followup, subsequent endoscopic/surgical findings and histopathology validated MR findings. RESULTS: In 23 patients with a high clinical suspicion of upper tract transitional cell tumors (TCC), 8 ureteral and 5 renal pelvic TCCs (2 bilateral) were diagnosed by MR, and confirmed histologically. In a further 5 patients benign causes for the hydronephrosis were found. No intrinsic or extrinsic pathology was demonstrable in 5 patients whose imaging findings were stable during 1 year of followup. CONCLUSIONS: MRU is a valuable noninvasive investigation for evaluating hydronephrosis in this group of patients with suspected urothelial cancer in which routine investigation had failed to provide clinically important information. Focused high resolution T2-weighted images were reliable in the diagnosis of ureteral and renal pelvic TCCs, and were valuable in excluding these and other mass lesions as the cause of hydronephrosis.
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We evaluated a 15% paste formulation of ponazuril in outbred Swiss mice that were experimentally infected with Eimeria vermiformis. Thirty, 8-week-old female mice (approximately 20 g) were placed in one group of 10 mice and one group of 20 mice. Mice in both groups were gavaged with approximately 5,000 sporulated oocysts of E. vermiformis on day 0. Mice in group 2 (n=10) were treated orally on days 3 and 4 with ponazuril (suspended in 30% propylene glycol) at the rate of 20 mg/kg. Mice in group 1 (n=20) were gavaged with a similar volume of 30% propylene glycol. Rates of oocyst passage (oocysts/g feces) were determined on day 10 (peak patency) for treated and nontreated mice using a fecal aliquot oocyst counting technique. Oocysts were not observed in the feces of treated mice using the aliquot technique. Control mice passaged oocysts at a geometric mean rate of >104,000 oocysts/g feces. Control mice also produced significantly less feces on day 10. These results indicate that ponazuril is effective against E. vermiformis under the conditions utilized in this study, and that the E. vermiformis mouse model could be useful in predicting the efficacy of new anticoccidial drugs.
Stable isotopic characterization or "fingerprinting" of active pharmaceutical ingredients (APIs) is a highly-specific means of defining the provenance of these pharmaceutical materials. The isotopic analysts in this study were provided with 20 blind samples of four APIs (tropicamide, hydrocortisone, quinine HCL, and tryptophan) from one-to-five production batch(es) from one-to-five manufacturer(s). Only the chemical identity of the APIs was initially provided to the isotopic analysts. Depending on the API chemical composition, isotopic ratios of either three or four elements (13C/12C, 15N/14N, 18O/16O, and/or D/H) were measured by either elemental analyzer/isotope ratio mass spectrometry (EA/IRMS: carbon (delta13C) and nitrogen (delta15N)) or by thermal conversion-EA/IRMS (TCEA/IRMS; hydrogen (deltaD) and oxygen (delta15N)); in all cases, the isotopic results are reported in the standard delta-notation which represents part-per-thousand () variations from the isotopic ratios of international standards. The stable isotopic analyses of the four suites of APIs spanned broad ranges in absolute value (deltadelta) and in estimated specificity (a product of dynamic ranges (DR, unitless)--note that these are upper limits of specificity because some of these isotope values may be partially interdependent). The five samples of tropicamide from one production batch and one manufacturer demonstrated the narrowest ranges (deltadelta13C=0.13 ; deltadelta15N=0.52 ; deltadelta18O=0.24 ; deltadeltaD=2.8 ) and the smallest specificity of 1:30.9. By contrast, the five samples of tryptophan that came from five separate manufacturers had some of the widest isotopic ranges observed (deltadelta13C=21.32 ; deltadelta15N=5.26 ; deltadelta18O=22.07 ; deltadeltaD=55.3 ) and had the largest specificity of 1:19.6 x 10(6). The isotopic provenance of the four suites of APIs readily emerged from bivariate plots of selected isotope ratios, particularly deltaD versus delta18O.
PURPOSE: We evaluated magnetic resonance urography (MRU) appearances in symptomatic hydronephrosis in pregnancy and compared urographic patterns in physiological and calculous disease. MATERIALS AND METHODS: A total of 24 consecutive pregnant women with symptomatic hydronephrosis underwent MRU, comprising an overview fast T2-weighted examination of the abdomen and pelvis, and thick slab, heavily T2-weighted MRU images, followed by focused, high resolution T2-weighted sequences obtained in an axial and coronal oblique plane through the level of ureteral caliber change. RESULTS: Of these 24 pregnant women 15 were found to have physiological hydronephrosis, 7 had calculous disease and 2 had preexisting urinary anomalies. MRU findings in physiological hydronephrosis cases were extrinsic compression of the middle third of the ureter, no filling defect and a collapsed ureter below it. Obstruction by ureteral calculi was seen at points of ureteral narrowing in the ureter, that is at the vesicoureteral junction in 2 cases, in the compressed mid ureter in 3 and at the pelviureteral junction in 1. Nonobstructive renal calculi were seen in another patient. Calculi presented throughout pregnancy but physiological hydronephrosis presented only in the late second and third trimesters. With distal calculi the MRU appearance was the double kink sign with constriction at the pelvic brim and the vesicoureteral junction with a standing column of urine in the pelvic ureter. There was renal edema and perirenal extravasation. Small calculi were only identified using high resolution T2-weighted magnetic resonance imaging. CONCLUSIONS: MRU is a valuable and well tolerated investigation for evaluating painful hydronephrosis in pregnancy. There are characteristic and differing urographic appearances in physiological and calculous obstruction.
A 3-yr-old secundiparous female ring-tailed lemur presented to the Auburn University Small Animal Clinic with signs of dyspnea, lethargy, and anorexia. The animal died before she could be examined, and a full necropsy was immediately performed. Provisional necropsy findings included moderate pneumonia and hepatopathy. Acute interstitial pneumonia and focal hepatocellular necrosis were confirmed histologically. Lung impression smears, histopathology, electron microscopy, immunohistochemistry, and tissue culture isolation resulted in a diagnosis of acute disseminated Toxoplasma gondii infection, which was confirmed by polymerase chain reaction. The isolate of T. gondii was avirulent for mice and was named AU Tgl and genetically is type II. The source of the infection remains unclear, but speculation suggests contaminated fruit or blackbirds (Passeriformes: Icteridae) acting as transport hosts for oocysts from nondomestic felids and feral cats on the property.
We have characterized growth and protein processing characteristics of Aspergillus niger strains carrying a disrupted allele of the previously cloned and characterized kexB gene [Appl. Environ. Microbiol. 66 (2000) 363] encoding a furin-type endoprotease. Deletion of the single-copy gene confirms it to be non-essential but disruptant strains exhibit a morphologically distinct phenotype characterized by hyperbranching. Processing of homologous pro-proteins and fusion proteins comprised of a heterologous protein fused down-stream of glucoamylase and separated at the fusion junction by an endoproteolytic cleavage site was compared in wildtype and mutant strains of A. niger. We show that maturation of the native glucoamylase requires KexB, whereas maturation of aspergillopepsin does not. The processing of fusion proteins carrying Lys-Arg requires KexB, although alternative endoproteases are capable of cleaving protein fusions at sites adjacent to Lys-Arg.
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OBJECTIVE: To survey medical students' views about the purposes and fairness of assessment procedures. METHOD: The survey used a 19-item questionnaire designed for self-completion. Respondents were invited to "strongly agree", "agree", "disagree" or "strongly disagree" with a series of statements about the purposes and fairness of assessment. There was space for free text comments relating to each statement. RESULTS: A total of 312 students out of a sample of 381 completed questionnaires (82% response rate). Whilst the majority of students (> 95%) agreed that ensuring competence, providing feedback and guiding student learning were important purposes of assessment, only half (51%) felt that assessment should be used to predict performance as a doctor. A clear majority of students (81%) agreed that, on the whole, assessment at Newcastle Medical School was fair. Data interpretation papers (comprising a combination of multiple true/false, "one best answer" and short answers) were perceived to be the fairest assessment tool; the assessment of clinical rotations by supervisors was perceived as the least fair. Differences in perception about the fairness of several assessment methods emerged between junior and senior students. A large number of respondents expressed desire for the provision of more feedback on performance in order to guide future learning. CONCLUSIONS: Whilst students' views about the fairness of specific assessment tools may sometimes be at variance with published research on assessment, their perceptions will influence the acceptability of assessment. Students would welcome the introduction of methods that provide meaningful assessment feedback.
Three-dimensional anal endosonography has enabled sagittal and coronal reconstructions of the anal canal to be matched with longitudinal pressure data, to present a combined picture of structure and function. This novel technique has been applied to a group of women with a clinical diagnosis of a third degree tear. Endosonography showed that only 68% of women had ultrasound evidence of sphincter damage. Anal canal anatomy and pressure profile did not differ significantly between those with and those without sphincter damage, but the anterior external anal sphincter and the puborectalis tended to be shorter and the pressures were lower in those with sphincter disruption.
OBJECTIVE: We aimed to evaluate whether chest CT alone is sufficient for follow-up assessment of patients with primary mediastinal B-cell lymphoma that is in remission. MATERIALS AND METHODS: A retrospective review of medical records and CT examinations of patients who received a diagnosis of primary mediastinal B-cell lymphoma between January 1989 and January 2000 was performed. The first-year follow-up comprised examinations at 3-month intervals of the neck, chest, abdomen, and pelvis, with the examination modality alternating between CT and gallium scintigraphy. Patients who achieved complete remission underwent the same CT protocol twice the following year and then once a year during sequential follow-up. RESULTS: Fifty-three patients with primary mediastinal B-cell lymphoma at presentation--31 females and 22 males, ranging in age from 17 to 61 years (average age at diagnosis, 34 years)--were studied. The follow-up time ranged from 6 to 143 months (average follow-up time, 42.4 months). Although 11 of the patients had only a partial remission, 42 patients (79%) achieved complete remission, with one patient lost to follow-up and thus excluded from study. Recurrence was diagnosed in six of these 42 patients. All six had mediastinal recurrence with additional involvement of the lungs, chest wall, pericardium, and pleura. One patient also had bone marrow involvement at recurrence. CONCLUSION: Recurrence of primary mediastinal B-cell lymphoma in patients who achieve complete remission appears to be confined to the chest. Consequently, chest CT alone is sufficient for routine follow-up of these patients.
AIM: To determine the incidence, imaging findings and prognostic significance of cerebral metastases and other cerebral events in women with ovarian cancer. METHOD: A 5-year retrospective review of all women with ovarian cancer who had cranial imaging was undertaken at two major gynaecological oncology centers. RESULTS: Of 1222 women under clinical review, 78 underwent cranial imaging and 13 (1.1%) had cerebral metastasis. Computed tomography (CT) was diagnostic of parenchymal disease in 12 and magnetic resonance imaging (MRI) showed leptomeningeal disease in two. The women were aged between 23 and 73 years and all had stage III or IV disease at presentation. Cerebral metastasis occurred at 6-60 months from initial diagnosis, with death occurring predominantly within 12 months, but with five survivors at 4-45 months. Of the remaining 65 women, 10 had cerebrovascular disease and three had unrelated lesions. CONCLUSION: Cerebral metastasis remains a rare event in women with ovarian cancer but may be an isolated late event associated with survival beyond a year after neurosurgery and chemotherapy. CT should be the first investigation as the incidence of cerebrovascular disease is similar to that of metastatic disease.
Equine protozoal myeloencephalitis (EPM) is the most important protozoal disease of horses in North America and it is caused by Sarcocystis neurona. Natural cases of encephalitis due to S. neurona have been reported in raccoons, Procyon lotor. We examined 99 raccoons for agglutinating antibodies to S. neurona using the S. neurona agglutination test (SAT) employing formalin-fixed merozoites as antigen. Raccoons originated in Florida (N=24, collected in 1996), New Jersey (N=25, collected in 1993), Pennsylvania (N=25, collected in 1999), and Massachusetts (N=25, collected in 1993 and 1994). We found that 58 (58.6%) of the 99 raccoons were positive for antibodies to S. neurona using the SAT; 44 of 99 raccoons (44%) had titers of > or =1:500. This prevalence is similar to the reported seroprevalence of 33-60% for S. neurona antibodies in horses from the United States using the Western blot test.