Biomedical subjects

S C Ward

Publications and source records attributed to S C Ward.

At least 19 recordsLinked to original sources

PubMed2001

Activities of linezolid against rapidly growing mycobacteria.

Linezolid is an oxazolidinone available as an oral drug which has activity against most gram-positive bacteria. However, few species of the genus Mycobacterium have been studied. We tested 249 clinical isolates and 10 reference strains of rapidly growing mycobacteria for susceptibility to linezolid by broth microdilution. Clinical species included the Mycobacterium fortuitum group (n = 74), M. abscessus (n = 98), M. chelonae (n = 50), M. mucogenicum (n = 10), and M. fortuitum third biovariant complex (10). The modal MIC for M. mucogenicum was 1.0 microg/ml, and the MIC at which 90% of the isolates tested are inhibited (MIC(90)) was 4 microg/ml; the modal MIC for the M. fortuitum group was 4 microg/ml, and the MIC(90) was 16 microg/ml; the modal MIC for the M. fortuitum third biovariant complex was 4 microg/ml, and the MIC(90) was 8 microg/ml; the modal MIC for M. chelonae was 8 microg/ml, and the MIC(90) was 16 microg/ml; and the modal MIC for M. abscessus was 32 microg/ml, and the MIC(90) was 64 microg/ml. Based on peak levels of linezolid in serum of 15 to 20 microg/ml, we propose the following broth MIC breakpoints for these species: susceptible, < or = 8 microg/ml; moderately susceptible, 16 microg/ml; and resistant, > or =32 microg/ml). These studies demonstrate the excellent potential of linezolid for therapy of rapidly growing mycobacteria.

Acetamides↗

PubMed2001

In vitro activities of linezolid against multiple Nocardia species.

Linezolid was tested by broth microdilution against 140 clinical Nocardia isolates belonging to seven species. The MIC at which 50% of the strains are inhibited (MIC50) and MIC90 for all species other than Nocardia farcinica were 2 and 4 microg/ml. Linezolid is the first antimicrobial agent demonstrated to be active against all Nocardia species.

Acetamides↗

PubMed2001

Checkpoint signals in grasshopper meiosis are sensitive to microtubule attachment, but tension is still essential.

The spindle checkpoint detects errors in kinetochore attachment to microtubules and delays anaphase if attachment is improper. The checkpoint is activated by attachment-sensitive components including Mad2 and certain phosphorylated proteins detected by the 3F3/2 antibody. We have studied Mad2 and 3F3/2 immunofluorescence in grasshopper spermatocytes. As in other cells, unattached kinetochores are loaded with Mad2 and are highly phosphorylated, whereas after proper attachment, Mad2 is lost and kinetochores are dephosphorylated. What is it about proper attachment that produces these changes--is it microtubule attachment itself or is it the tension from mitotic forces that follows proper attachment? Using micromanipulation, we created an intermediate state, weak attachment, that provides an answer. Weakly attached kinetochores are not under tension and have few kinetochore microtubules. Despite the absence of tension, many weakly attached kinetochores lose their Mad2 and become dephosphorylated. Therefore we conclude that microtubule attachment determines both Mad2 binding and phosphorylation. Nevertheless, tension plays an absolutely essential role. Tension elevates the number of kinetochore microtubules to the level necessary for the complete loss of Mad2 and dephosphorylation from all kinetochores. This gives a reliable 'all clear' signal to the checkpoint, allowing the cell to progress to anaphase.

Animals↗

PubMed2000

Squamous cell carcinoma of the hallux.

This article reports on a case of malignant degeneration of a hallux nail bed ulcer of 30 years' duration. Histologically, this lesion was determined to be a squamous cell carcinoma, a type of lesion that is also known as Marjolin's ulcer. The diagnosis, histologic findings, and treatment of patients with cutaneous squamous cell carcinoma are discussed.

Aged↗

PubMed1999

Developmental sex differences in amino acid neurotransmitter levels in hypothalamic and limbic areas of rat brain.

GABA, glutamate and aspartate are the predominant amino acid neurotransmitters in the mammalian brain. We have previously reported a developmental sex difference in messenger RNA levels of glutamate decarboxylase, the rate-limiting enzyme in GABA synthesis [Davis A. M. et al. (1996) Horm. Behav. 30, 538-552]. Males were found to have significantly higher levels of messenger RNA in many steroid-concentrating regions of the hypothalamus and limbic system on day 1 of life. Therefore, in this study, we have examined levels of amino acid neurotransmitters during early postnatal development in many of the same or related brain areas. We found that levels of all three transmitters change as animals age. While both GABA and aspartate concentrations increase, glutamate levels decrease. In addition, there are sex differences in neurotransmitter levels in several areas examined, including the ventromedial and arcuate nuclei of the hypothalamus, and the CA1 region of the hippocampus. Sex differences for GABA occur only on postnatal days 1 and 5. However, sex differences in aspartate occur later in development (postnatal day 20). The CA1 region of males has a significantly greater concentration of GABA, glutamate and aspartate than females on postnatal day 1. In addition, treatment of females with testosterone propionate on the day of birth results in increased GABA levels, suggesting that these sex differences may be the result of hormone exposure during development. We hypothesize that these hormonally mediated sex differences in amino acid transmitters early in development contribute to the establishment of sexually dimorphic neuronal architecture in the adult.

Aging↗

PubMed1999

Preoperative magnetic resonance staging of rectal cancer with an endorectal coil and dynamic gadolinium enhancement.

BACKGROUND: The aim of the study was to assess the value of endorectal coil magnetic resonance imaging (MRI) with gadolinium enhancement in the preoperative staging of rectal cancer. METHODS: In addition to standard evaluation, patients with rectal lesions were assessed by MRI obtained with a pelvic phased-array coil in combination with an endorectal coil. RESULTS: The study group comprised 29 patients with rectal cancer staged with an endorectal coil who had surgery without preoperative adjuvant therapy. In addition to standard T1- and T2-weighted images, dynamic contrast-enhanced images were acquired in all patients. Considerable interobserver variation was noted, particularly for pathological tumour stage pT1 or pT2 (kappa = 0.36). Compared with pathological findings, endorectal MRI correctly staged nine patients, overstaged 16 and understaged four. Whilst lymph node metastases were accurately detected in 70 per cent of patients, the positive predictive value was only 58 per cent. CONCLUSION: MR staging of rectal cancer with an endorectal coil and gadolinium enhancement is inaccurate for early tumours (stage T1 or T2) and is associated with a considerable degree of interobserver variation for individual scan sequences.

Gadolinium DTPA↗

PubMed1998

Tension-sensitive kinetochore phosphorylation in vitro.

Many cells have a checkpoint that detects a single misattached chromosome and delays anaphase, allowing time for error correction. Detection probably depends on tension-sensitive kinetochore protein phosphorylation. Somehow, mechanical tension, or some consequence of tension, produces a chemical change, dephosphorylation. The mechanism of tension-mediated dephosphorylation can be approached using an in vitro system. Earlier work showed that the kinetochores of washed chromosomes from a mammalian cell line can be phosphorylated in vitro simply by incubation with ATP and a phosphatase inhibitor. We confirm this for chromosomes from insect meiotic cells. Thus, kinetochores of washed chromosomes from diverse sources contain a complete phosphorylation system: a kinase, a phosphatase and the substrate protein(s). We show that phosphorylation in vitro is sensitive to tension, as it is in living cells. This makes the conditions required for phosphorylation in vitro relevant to the process in living cells. The phosphatase is ruled out as the tension-sensitive component in vitro, leaving either the kinase or the substrate as the sensitive component. We show that a kinase extracted from mammalian cells in mitosis phosphorylates the kinetochores of insect meiotic chromosomes very effectively. The mammalian kinase under-phosphorylates the kinetochore of the insect's X-chromosome, just as the native insect kinase does. This provides a clue to the evolution of a chromosome that is not detected by the checkpoint. The mammalian kinase is not tightly bound to the chromosome and thus functions primarily in solution. This suggests that the substrate's phosphorylatable groups are freely available to outside constituents, e.g. regulators, as well as to the kinetochore's own kinase and phosphatase.

Adenosine Triphosphate↗

PubMed1997

Subnasoalveolar anatomy and hominoid phylogeny: evidence from comparative ontogeny.

The present analysis evaluated extant hominoid subnasal morphological variation from an ontogenetic perspective, documenting both qualitative and allometric details of subnasal maturation in Hylobates, great apes and modern humans. With respect to intraspecific variation, results of log-linear modeling procedures indicate that qualitative features of the subnasal region shown previously to discriminate extant taxa (Ward and Kimbel, 1983; McCollum et al., 1993) do not vary appreciably with either age or sex. In terms of quantitative variation, aside from observed changes in the position of the anterior attachment of the nasal septal cartilage relative to the lateral margins of the nasal cavity, the morphology of the subnasal region does not vary appreciably with age. Furthermore, it was found that sexual dimorphism in subnasal form is present only in Pongo and Gorilla and is the result of sexual bimaturism rather than sexual variation in canine size. In considering interspecific variation in subnasal form, there is a propensity among hominoid taxa for the nasal cavity floor to be free of substantial topographic relief. The smoothly continuous nasal floor topography identified in the majority of hominoid taxa appears to be produced by extensive resorption of the anterior nasal cavity floor that accompanies an upward rotation of the anterior maxilla during craniofacial ontogeny. Comparisons of ontogenetic allometric trajectories indicate that relatively little of the variation in hominoid subnasal form can early be attributed to variation in body/cranial size. Instead, variation in craniofacial orientation, vascular anatomy and incisor size and inclination were identified as potential mediators of hominoid subnasoalveolar anatomy. Although results of this analysis confirm that many detail of the orangutan subnasal morphology are derived for this taxon, there is only little conclusive evidence to support recent reports that the morphology displayed by Gorilla is primitive for great apes.

Aging↗

PubMed1996

Hepatic angiomyelolipoma and tuberous sclerosis.

A patient with angiomyelolipoma of the liver, together with radiological evidence of pancreatic, renal and bony lesions characteristic of tuberous sclerosis, is described. Although the patient had no other clinical features of tuberous sclerosis, her daughter was found to suffer from the classical triad of this syndrome and also has had hepatic lipomatous lesions and bony involvement. This is the first histologically proven case of hepatic angiomyelolipoma associated with tuberous sclerosis.

Angiolipoma↗

PubMed1995

Radiation pneumonitis after selective internal radiation treatment with intraarterial 90yttrium-microspheres for inoperable hepatic tumors.

PURPOSE: To investigate the clinical, histopathological, and radiological features of radiation pneumonitis arising as a complication of selective internal radiation treatment for liver tumors. To correlate the development of radiation pneumonitis with the degree of lung shunting as assessed by 99mTechnetium-labeled macroaggregated albumin (Tc-MAA) scan. METHODS AND MATERIALS: Five out of 80 patients who had inoperable hepatic tumors and underwent treatment with intraarterial 90Yttrium- (90Y)-microspheres, developed progressive restrictive ventilatory dysfunction without an infective or cardiovascular cause. Histopathological evidence of a pneumonitis and the presence of microspheres in the lung tissue suggested a diagnosis of radiation pneumonitis. The clinical course, radiological and histopathological findings, percentage tumor shunting to the lungs (lung shunting, as predicted by gamma camera scanning after intraarterial Tc-MAA), and the estimated radiation dose to the lungs were analyzed. In an attempt to reduce pulmonary shunting of the microspheres, three patients received partial hepatic embolization with inert particles before selective internal radiation therapy. RESULTS: In the five patients who developed radiation pneumonitis, lung shunting percentages (as predicted by Tc-MAA scan) ranged from 13.1 to 45.6% (median 23.7%). The estimated whole lung radiation dose ranged from 10.43 Gy to 36.44 Gy (median 25.04 Gy). Among 75 patients who did not develop radiation pneumonitis, the percentage lung shunting ranged from less than 1% to 15% (median 6%). Nine patients had lung shunting greater than 13% and five of them developed radiation pneumonitis, whereas this developed in none of those in whom shunting was below 13%. The onset of radiation pneumonitis ranged from 1 to 6 months after internal radiation treatment. All five patients exhibited characteristic plain radiographic and computerized tomographic changes comprising extensive consolidation with well-defined lateral margins. Clinical improvement after corticosteroid treatment was seen in two patients. Three patients died from respiratory failure and two from other causes. Partial hepatic arterial embolization reduced the degree of lung shunting to less than 13%, but did not prevent the development of radiation pneumonitis. CONCLUSION: Radiation pneumonitis may become a complication after intraarterial 90Y-microspheres treatment when lung shunting, as assessed by Tc-MAA scan, is high (above 13%). Prescribed activity of 90Y and lung shunting of Tc-MAA should be considered together before giving selective internal radiation (SIR) therapy for hepatic tumors, and preferably avoided if the lung shunting is above 13%.

Adult↗

PubMed1995

A prospective study of upper gastrointestinal hemorrhage in patients with hepatocellular carcinoma.

Our purpose was to determine, in a prospective study, the causes of gastrointestinal hemorrhage in patients with hepatocellular carcinoma, and the relationship of portal vein invasion with variceal hemorrhage in these patients. During an 11-month period, 55 patients presented with hepatocellular carcinoma presented with signs and/or symptoms of upper gastrointestinal hemorrhage. Forty-seven percent had bleeding from varices, whereas the majority, 53%, had a nonvariceal bleeding source. Among those with nonvariceal bleeding, duodenal ulceration was the commonest cause. Direct tumor invasion into the gastrointestinal tract was found in three patients. Tumor invasion of the portal venous system was detected by ultrasound examination in 76% of the variceal bleeders, compared to only 45% of the nonvariceal bleeders. Despite the very high frequency of cirrhosis among patients with hepatocellular carcinoma, the source of bleeding was variceal in less than half of the patients. Portal vein invasion is a risk factor for subsequent variceal bleed.

Carcinoma, Hepatocellular↗

PubMed1995

Ultrasound demonstration of lymph nodes in the hepatoduodenal ligament ('Daisy Chain nodes') in normal subjects.

We describe the ultrasound appearances of lymph nodes in the hepatoduodenal ligament ('Daisy Chain Nodes') in normal subjects. Nodes were identified in 69 of 116 patients referred for abdominal ultrasound, who had no underlying reason for lymphadenopathy. Patients with primary malignancy or inflammatory pathologies were excluded from the sample. In 26 patients, the hepatoduodenal ligament (HDL) was not visualized. Therefore Daisy Chain nodes were visualized in 77% of patients where the HDL was visualized. Nodes were seen more frequently in younger patients; this was attributed to more homogeneous hyperechoic perinodal fat in the younger age group and the larger size of nodes in young patients. Study of normal lymph nodes will help to determine criteria for the appearances of pathological nodes in the abdomen.

Adolescent↗

PubMed1995

Kinetochore chemistry is sensitive to tension and may link mitotic forces to a cell cycle checkpoint.

Some cells have a quality control checkpoint that can detect a single misattached chromosome and delay the onset of anaphase, thus allowing time for error correction. The mechanical error in attachment must somehow be linked to the chemical regulation of cell cycle progression. The 3F3 antibody detects phosphorylated kinetochore proteins that might serve as the required link (Gorbsky, G. J., and W. A. Ricketts. 1993. J. Cell Biol. 122:1311-1321). We show by direct micromanipulation experiments that tension alters the phosphorylation of kinetochore proteins. Tension, whether from a micromanipulation needle or from normal mitotic forces, causes dephosphorylation of the kinetochore proteins recognized by 3F3. If tension is absent, either naturally or as a result of chromosome detachment by micromanipulation, the proteins are phosphorylated. Equally direct experiments identify tension as the checkpoint signal: tension from a microneedle on a misattached chromosome leads to anaphase (Li, X., and R. B. Nicklas. 1995. Nature (Lond.). 373:630-632), and we show here that the absence of tension caused by detaching chromosomes from the spindle delays anaphase indefinitely. Thus, the absence of tension is linked to both kinetochore phosphorylation and delayed anaphase onset. We propose that the kinetochore protein dephosphorylation caused by tension is the all clear signal to the checkpoint. The evidence is circumstantial but rich. In any event, tension alters kinetochore chemistry. Very likely, tension affects chemistry directly, by altering the conformation of a tension-sensitive protein, which leads directly to dephosphorylation.

Animals↗

PubMed1995

MRI of intraspinal nerve sheath tumours presenting with sciatica.

The magnetic resonance imaging (MRI) characteristics of 14 intraspinal nerve sheath tumours (NST) presenting with sciatica were reviewed. The group comprised seven schwannomas, six neurofibromas and one perineuroma. The tumours were either iso- or hypointense with respect to spinal cord on T1-weighted (T1W) images; almost all tumours were hyperintense compared with spinal cord on T2-weighted (T2W) images. The tumours were all detectable on unenhanced T1W images. Nine NST were scanned following Gadolinium-Diethylenetriamine penta acetic acid (DTPA) injection and all showed intense enhancement. This aids differentiation from sequestrated disc fragments. Tumours were more likely to show homogeneous enhancement unless they were recurrent tumours. Rim enhancement occurs more commonly in schwannomas and this can be used to differentiate these from neurofibromas. However, on unenhanced images, schwannomas cannot be distinguished from neurofibromas. Four tumours occurred at T11-T12. There was poor correlation of the site of the lesion with the clinical findings. MRI studies in patients with sciatica should include the lower thoracic region especially if no protruded disc was found in the lumbar region.

Adolescent↗

PubMed1995

Technical note: an evaluation of the routine use of rectal air in computed tomography of the pelvis.

We have performed computed tomographic examinations of the pelvis in 50 patients, using rectally administered air to outline the rectosigmoid colon. Bowel cleansing was not performed and smooth muscle relaxants were not used. The procedure was well tolerated by all patients, and diagnostic images were obtained in all cases. There were no complications. This is a safe, low cost and easily administered form of bowel contrast. We recommend it as the technique of choice in routine pelvic computed tomography.

Colon, Sigmoid↗

PubMed1994

The role of immediate cytological evaluation in CT-guided biopsy.

A prospective study of 130 fine-needle aspiration biopsies (FNAB) was performed on 110 consecutive patients to assess the contribution of immediate cytological evaluation (ICE). All biopsies were performed under CT guidance using either 20 gauge or 22 gauge aspiration needles. Two distinct patient groups were derived from two hospitals. In one hospital a consultant cytologist was usually present, whereas in the other immediate cytological evaluation was not generally available. Overall, a consultant cytologist was present for 52% of the biopsies. The accuracy of the procedure, the number of needle passes made, the complication rates with and without ICE were assessed for each hospital population group. The overall accuracy, with and without ICE, was 72%. Although slightly fewer specimens were deemed inadequate when ICE was available, this difference did not reach statistical significance.

Biopsy, Needle↗

PubMed1994

Elements of error correction in mitosis: microtubule capture, release, and tension.

The correction of certain errors in mitosis requires capture and release: new kinetochore microtubules must be captured and old, misdirected ones must be released. We studied capture and release in living grasshopper spermatocytes. Capture is remarkably efficient over a broad range in the angle at which a microtubule encounters a kinetochore. However, capture is inefficient when kinetochores point directly away from the source of properly directed microtubules. Capture in that situation is required for correction of the most common error; microtubule-kinetochore encounters are improbable and capture occurs only once every 8 min, on average. Release from the improper attachment caused by misdirected microtubules allows kinetochore movement and the completion of error correction. We tugged on kinetochores with a micromanipulation needle and found they are free to move less than one time in two. Thus error correction depends on two improbable events, capture and release, and they must happen by chance to coincide. In spermatocytes this will occur only once every 18 min, on average, but a leisurely cell cycle provides ample time. Capture and release generate only change, not perfection. Tension from mitotic forces brings change to a halt by stabilizing the one correct attachment of chromosomes to the spindle. We show that tension directly affects stability, rather than merely constraining kinetochore position. This implies that chromosomes are attached to the spindle by tension-sensitive linkers whose stability is necessary for proper chromosome distribution but whose loss is necessary for the correction of errors.

Animals↗

PubMed1994

A clinical comparison between conventional and digital mammography utilizing computed radiography.

Previous work utilizing a specially designed mammographic test object has indicated that the image quality of computed radiography (CR) approaches that of a conventional film-screen technique of equivalent radiographic speed. In an attempt to correlate these results with the clinical situation a subjective rating study of the primary physical parameters of noise, sharpness, and contrast has been conducted. Using a randomized viewing sequence two radiologists experienced in mammography were asked to score these parameters utilizing a 5 point scale. A total of 138 images was used, 62% containing no abnormalities and 38% containing either microcalcifications, masses or both. Additionally, the observers scored their confidence of correct classification, and these results were then used to construct receiver operating characteristic (ROC) curves. The subjective rating of the physical parameters results produced similar results to those obtained using the test object, with CR images providing greater contrast than film. The resolution of CR, however, was lower than for film. Overall the noise levels were similar for both modalities, but the digital images occasionally contained high levels of dust artefacts. In one case these artefacts were mistaken for a cluster of microcalcifications. The test object results and the parameter rating results indicate that CR approaches the performance of film-screen images. Statistically the ROC curves produced indicate CR images to be comparable to the film-screen combination. This may be because the increased contrast compensates for resolution limitations and these findings correlate with our clinical experience.

Breast Diseases↗