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Biomedical subjects

S D Allen

Publications and source records attributed to S D Allen.

At least 19 recordsLinked to original sources

Variation of mesorectal volume with abdominal fat volume in patients with rectal carcinoma: assessment with MRI.

The purpose of this study was to assess the variability in the volume of the mesorectum in patients with rectal carcinoma. A retrospective review was made of pelvic MRI studies in 30 patients (mean age 64 years, range 34-88 years, 18M:12F) with histologically proven rectal carcinomas that were confined to the mesorectum. The outer low signal margin of the mesorectum was traced, over at least 10 consecutive 10 mm contiguous slices, until its disappearance. The visceral fascial compartment, body cross-sectional area and body mass index were measured, on a solitary slice, at the level of the L5/S1 disc. Linear regression was calculated for independent determinants of the mesorectal volume. Mean mesorectal volume in males was 227.5 cm3 (95%CI 191.6-263.4), and in females was 157.5 cm3 (95%CI 129.3-185.7). The difference in mesorectal volume between men and women was statistically significant (p<0.001). Mean visceral compartment area in males was 18.4 cm2 (95%CI 16.3-20.5) and in females was 14.6 cm2 (95%CI 12.8-16.4). Visceral compartment area correlated with mesorectal area and volume in females (p<0.05), and extremely well in males (p<0.005). Body cross-sectional area, body mass index and age did not correlate with mesorectal size. The correlation of visceral compartment area with mesorectal volume and mean area suggests that the mesorectum is determined in a similar way to other body fat compartments, with a similar anatomical variation. This significant variation in size and volume may have an important prognostic implication in patients with rectal carcinoma. This volume can be measured and reported on pre-operative MRI scanning and may be communicated to surgeons and radiotherapists.

Abdominal Fat↗

Imaging of Wegener's granulomatosis.

Wegener's granulomatosis is an uncommon multisystemic disorder of unknown aetiology. It is characterized histopathologically by necrotizing granulomatous vasculitis. Most commonly this involves the upper and lower respiratory tract, with pulmonary involvement occurring at some stage of the disease in almost all patients. However, many other organ systems can also be affected including the kidneys, orbits and central nervous system. For this pictorial review, we have assessed the imaging of 155 patients over a 10-year period in order to illustrate characteristic and some of the more unusual imaging features of Wegener's granulomatosis.

Adult↗

Radiology of gestational trophoblastic neoplasia.

Gestational trophoblastic neoplasia (GTN) encompasses a broad spectrum of placental lesions from the pre-malignant hydatidiform mole (complete and partial) through to the malignant invasive mole, choriocarcinoma and rare placental site trophoblastic tumour (PSTT). Ultrasound remains the radiological investigation of choice for initial diagnosis, and it can also predict invasive and recurrent disease. Magnetic resonance imaging is of invaluable use in assessing extra-uterine tumour spread, tumour vascularity, and overall staging. Positron emission tomography and computed tomography undoubtedly have a role in recurrent and metastatic disease, while angiography has a place in disease and complication management. This review will describe the relevant pathophysiology and natural history of GTN, and the use of imaging techniques in the diagnosis and management of these conditions.

Female↗

Clostridium clostridioforme: a mixture of three clinically important species.

Clostridium clostridioforme shows much variability in phenotypic and antimicrobial susceptibility tests, suggesting it may be more than a single species even though all strains share unique morphology. This study was designed to determine if there are multiple species and, if so, to demonstrate the differences that exist between them. A total of 107 strains of C. clostridioforme were investigated by sequencing of the 16S rRNA gene, phenotypic studies, and antimicrobial susceptibility testing. In addition, clinical data from patients whose infections yielded an organism identified as C. clostridioforme was reviewed. Data from the above studies revealed three principal species in what has been called C. clostridioforme: Clostridium bolteae, C. clostridioforme, and Clostridium hathewayi. Each species may be distinguished by certain phenotypic tests. All three species were involved in infections, including bacteremia. C. clostridioforme appears to be associated with more serious or invasive human infections than the other two species in the group. Resistance to penicillin G is common and is due to beta-lactamase production. Resistance to clindamycin and moxifloxacin is also seen. The three species differ in terms of virulence and antimicrobial resistance. "C. clostridioforme" actually represents three distinct species that are different in terms of 16S rRNA sequences, phenotypic characteristics, and antimicrobial susceptibility. It is important for microbiology laboratories to distinguish between these species and for clinicians to be aware of the differences between them.

Anti-Bacterial Agents↗

Therapeutic peptidomimetic strategies for autoimmune diseases: costimulation blockade.

Cognate interactions between immune effector cells and antigen-presenting cells (APCs) govern immune responses. Specific signals occur between the T-cell receptor peptide and APCs and nonspecific signals between pairs of costimulatory molecules. Costimulation signals are required for full T-cell activation and are assumed to regulate T-cell responses as well as other aspects of the immune system. As new discoveries are made, it is becoming clear how important these costimulation interactions are for immune responses. Costimulation requirements for T-cell regulation have been extensively studied as a way to control many autoimmune diseases and downregulate inflammatory reactions. The CD28:B7 and the CD40:CD40L families of molecules are considered to be critical costimulatory molecules and have been studied extensively. Blocking the interaction between these molecules results in a state of immune unresponsiveness termed 'anergy'. Several different strategies for blockade of these interactions are explored including monoclonal antibodies (mAbs), Fab fragments, chimeric, and/or fusion proteins. We developed novel, immune-specific approaches that interfere with these interactions. Using experimental autoimmune encephalomyelitis (EAE), an animal model for multiple sclerosis mediated by central nervous system (CNS)-specific T-cells, we developed a multi-targeted approach that utilizes peptides for blockade of costimulatory molecules. We designed blocking peptide mimics that retain the functional binding area of the parent protein while reducing the overall size and are thus capable of blocking signal transduction. In this paper, we review the role of costimulatory molecules in autoimmune diseases, two of the most well-studied costimulatory pathways (CD28/CTLA-4:B7 and CD40:CD40L), and the advantages of peptidomimetic approaches. We present data showing the ability of peptide mimics of costimulatory molecules to suppress autoimmune disease and propose a mechanism for disease suppression.

Amino Acid Sequence↗

Imaging of intra-articular osteoid osteoma.

Intra-articular osteoid osteoma accounts for approximately 13% of all osteoid osteomas and presents as a monoarthropathy. Radiographs commonly do not identify the nidus, and in this event, MRI is likely to be the next imaging investigation. MRI may show a variety of appearances depending upon the age of the lesion. This article illustrates the imaging features of intra-articular osteoid osteoma, with emphasis on MRI. CT remains the investigation of choice for identifying the nidus.

Adolescent↗

The photodimerisation of trans-cinnamic acid and its derivatives: a study by vibrational microspectroscopy.

Infrared and Raman spectroscopies have been used to monitor the [2 + 2] photodimerisation reactions of alpha-trans-cinnamic acid and of a number of its derivatives. The principal changes observed in the spectra upon dimerisation are decay of a band around 1637 cm(-1), which is assigned to v(C=C) of the ethene bond of the monomer, and growth of bands just above 3000 cm(-1), which result from v(C-H) of saturated carbon atoms of the dimer. The use of microscope attachments has allowed us to follow the reactions of single crystals and we conclude that the reactions are topotactic in nature. We have carried out preliminary kinetic experiments in which spectra of one single crystal are recorded after sequential periods of photolysis. We find that the rates of dimerisation of differently substituted cinnamic acids are similar, with physical effects, such as the thickness of an individual crystal, outweighing any observed electronic effects (inductive or mesomeric).

Cinnamates↗

Diagnosis of Pneumocystis carinii pneumonia in human immunodeficiency virus-infected patients with polymerase chain reaction: a blinded comparison to standard methods.

Pneumocystis carinii pneumonia (PCP) is an important cause of morbidity and death among persons with human immunodeficiency virus (HIV) infection. Polymerase chain reaction (PCR) analysis of respiratory specimens has been investigated as a rapid diagnostic method. We have previously reported on the utility of this technique for diagnosing PCP in HIV-infected patients. In this report we evaluate PCR used in a blinded study design to avoid biases inherent to retrospective and nonblinded studies. The diagnosis of PCP was established on the basis of clinical findings and morphological studies of bronchoalveolar lavage (BAL) and/or lung biopsy specimens before PCR testing. PCR was performed without knowledge of the diagnosis. PCR results were graded from "negative" to 3+ on the basis of intensity of the banding pattern. Forty-seven patients were enrolled in the study, including 18 with proven PCP and 29 with other conditions. PCR was positive at grade 1 or higher for all 18 patients with PCP (100% sensitivity), at grade 2 or higher for 13 patients (72.2% sensitivity), and at grade 1 or higher for 4 of the 29 control patients (specificity of 86.2%). If a grade 2 or higher was required for diagnosis, the specificity improved to 100%. Results were reproducible with testing of a second aliquot for 46 of 47 patients (97.8%). Our findings confirm that PCR is a sensitive and reproducible test for detection of P. carinii in BAL specimens. Problems with false-positive results for control patients, however, limit the applicability of this method.

AIDS-Related Opportunistic Infections↗

Typing of Histoplasma capsulatum isolates based on nucleotide sequence variation in the internal transcribed spacer regions of rRNA genes.

The nucleotide sequences of internal transcribed spacer (ITS) regions of rRNA genes of 24 isolates of Histoplasma capsulatum were examined. The results indicate that the sequences of ITS regions in different isolates are not identical. Sequence variations were found at 20 positions in the 496 bp that were sequenced. Ten different sequence patterns, designated types A through H, were observed when the sequences from the 24 isolates were aligned. Twelve isolates from Indianapolis were classified into four different types. Two isolates from New York belonged to type G. Three isolates from different cities were type F. The remaining six isolates were of different types.

Acquired Immunodeficiency Syndrome↗

Efficacy of syringomycin E in a murine model of vaginal candidiasis.

Syringomycin E (SR-E), a new antifungal produced by the bacterium Pseudomonas syringae pv. syringae, was evaluated in a murine vaginal candidiasis model. In one study, mice were treated intravaginally b.i.d. for 4 days with drug carrier, SR-E 2% in either PEG-400 or PEG-ointment, or 1% clotrimazole as a positive control. Quantitative vaginal cultures were taken prior to treatment on day 1 and on days 5, 6, and 7. Both formulations showed a reduction of yeast colonization in the vaginas on day 5 (P< or =0.06 and P< or =0.03 for SR-E/PEG-400 and SR-E/PEG ointment, respectively) and SR-E/PEG ointment reduced the colonization on day 7 (P< or =0.06) when compared to carrier treated controls. In a second study, SR-E was formulated in Aquaphor at three higher concentrations of SR-E [3%, 6%, or 12% (w/v)]. SR-E showed dose-dependent efficacy. The 3% dose showed no effect while the 6% and 12% doses reduced the number of yeasts. The 12% dose showed a significant reduction on days 5 (P< or =0.01), 6 (P< or =0.06), and 7 (P< or =0.03) when compared with the drug carrier controls and on day 5 was more effective than clotrimazole (P< or =0.03). Clotrimazole did not significantly reduce the yeasts in the vagina until days 6 (P< or =0.01) and 7 (P< or =0.01) when compared to the drug carrier controls. No vaginal inflammatory response was evident by histological examination in uninfected animals treated with SR-E. No SR-E could be detected in plasma, kidney, or liver. SR-E (12%) was an effective treatment when compared to 1% clotrimazole.

Animals↗

Reproducibility of broth microdilution and disk diffusion susceptibility tests of nine antimicrobial agents against Streptococcus pneumoniae ATCC 49619.

Collaborative studies documented the reproducibility of broth microdilution susceptibility tests of Streptococcus pneumoniae against nine antimicrobial agents and of disk diffusion tests with six of those drugs. Replicate tests of Streptococcus pneumoniae ATCC 49619 in five different laboratories led to the following provisional quality control limits: cefdinir--0.03 to 0.25 microgram/ml and 26 to 31 mm; cefetamet--0.5 to 2 micrograms/ml and 20 to 25 mm; ciprofloxacin--0.25 to 1 microgram/ml and 20 to 26 mm; clinafloxacin--0.03 to 0.125 microgram/ml and 28 to 34 mm; grepafloxacin--0.06 to 0.5 microgram/ml and 21 to 28 mm; PD131628--0.125 to 0.5 microgram/ml and 24 to 29 mm; clindamycin--0.03 to 0.12 microgram/ml; cefpodoxime--0.03 to 0.12 microgram/ml; and trospectomycin--1 to 4 microgram/ml (disk tests were not evaluate for the latter three drugs).

Anti-Bacterial Agents↗

Rapid and effective method for preparation of fecal specimens for PCR assays.

We have developed a novel method for the preparation of fecal specimens for PCR assays. Approximately 100 mg of solid stool or 200 microliters of liquid fecal sample was thoroughly suspended in 1 ml of water. Fecal debris was removed by low-speed centrifugation (2,800 x g for 2 min). The supernatant was then boiled for 10 min in a water bath and further clarified by high-speed centrifugation (12,000 x g for 5 min). Fifty microliters of the clarified supernatant was then purified by Sepharose CL-6B spin column chromatography, and a portion of the purified supernatant was used for PCR. By this method, stools containing enterotoxigenic Escherichia coli H10407 were amplified by colonization factor antigen I fimbrial gene PCR, with a sensitivity of 100 organisms per reaction. The method was also effective for processing stool specimens for Clostridium difficile toxin A and B gene PCRs. This method is rapid, effective, and simple to perform and will improve the applications of PCR to stool specimens for diagnostic purposes.

Bacterial Typing Techniques↗

Methods of measuring susceptibility of anaerobic bacteria to trovafloxacin, including quality control parameters.

Three methods approved by the National Committee for Clinical Laboratory Standards for testing the susceptibility of anaerobic bacteria were used to evaluate the fluoroquinolone, trovafloxacin. The methods gave essentially comparable results with 126 anaerobes and with three quality control strains. A collaborative study defined the quality control range for trovafloxacin MICs. Trovafloxacin had good in vitro activity against the more common anaerobes (MIC 90 < = or 2.0 micrograms/ml).

Anti-Infective Agents↗

Tentative interpretive criteria and quality control parameters for in-vitro susceptibility testing of Neisseria gonorrhoeae to two fluoroquinolones (PD 131628 and grepafloxacin (OPC 17116)).

The susceptibility of Neisseria gonorrhoeae to PD 131628 and grepafloxacin (OPC 17116) was evaluated by agar dilution and disc diffusion methods. A tentative susceptibility category for both fluoroquinolones included strains for which the MICs are < or = 0.06 mg/L and the zones of inhibition are > or = 38 mm for PD 131628 and > or = 37 mm for grepafloxacin. Quality control studies with N. gonorrhoeae ATCC 49226 suggested that agar dilution MIC limits were 0.002-0.008 mg/L and 0.004-0.03 mg/L for PD 131628 and grepafloxacin, respectively. The zone size limits were 50-58 mm for PD 131628 and 44-52 mm for grepafloxacin.

Anti-Infective Agents↗

In-vitro susceptibility of Streptococcus pneumoniae to the d- and l-isomers of ofloxacin: interpretive criteria and quality control limits.

The l-isomer of ofloxacin (levofloxacin) was twice as active as ofloxacin and the d-isomer was inactive against 654 Streptococcus pneumoniae isolates. For disc susceptibility tests of pneumococci, 5 micrograms levofloxacin discs can be used with interpretive criteria of < or = 12 mm for resistant (MIC > or = 8.0 mg/L) and > or = 16 mm for susceptible (MIC < or = 2.0 mg/L). For quality control of levofloxacin tests, S. pneumoniae ATCC 49619 should give zones 20-25 mm in diameter and MICs 0.5-2.0 mg/L.

Anti-Infective Agents↗

Multicenter evaluation of four methods for Clostridium difficile detection: ImmunoCard C. difficile, cytotoxin assay, culture, and latex agglutination.

A three-center study was undertaken to compare several test methods for the detection of Clostridium difficile, associated toxin, or related markers by using 927 stool specimens. Methods included direct assay of cytotoxin in stool by tissue culture, C. difficile bacterial culture followed by cytotoxin assay, bacterial culture alone, latex agglutination assay, and the ImmunoCard C. difficile test (Meridian Diagnostics, Inc.). The sensitivities, as determined against direct cytotoxin assay results, of the ImmunoCard C. difficile and latex agglutination assays were 84 and 67%, respectively (92 and 77%, respectively, when adjusted for bacterial culture outcomes). Evaluation for C. difficile-associated disease (CDAD) among 864 patients was based on clinical criteria for antibiotic-associated diarrhea combined with laboratory evidence of toxin or toxin-producing C. difficile in stool specimens. The sensitivity of each test method for screening of CDAD was as follows: bacterial culture, 95%; culture with cytotoxin assay of isolates, 90%; ImmunoCard C. difficile test, 83%; cytotoxin assay 82%; and latex agglutination assay, 67% (P < or = 0.05 versus all other methods). The standard deviations of the test sensitivity statistics between study sites were ranked as follows: cytotoxin assay (+/- 3.1%) < ImmunoCard C. difficile test (+/- 5.7%) < latex agglutination assay (+/- 12.3%) < culture (+/- 24.7%) < culture with cytotoxin assay (+/- 28.0%). The data support the use of the ImmunoCard C. difficile test as an adjunct for the diagnosis of CDAD.

Bacterial Toxins↗

Recurrent herpes labialis as a potential risk factor for nonarteritic anterior ischemic optic neuropathy.

This case-control study was undertaken to determine if recurrent herpes labialis posed an independent risk factor for the development of nonarteritic anterior ischemic optic neuropathy among individuals with small optic nerve cup:disk ratio. The study population was comprised of 43 nonarteritic anterior ischemic optic neuropathy cases and 30 consecutive control subjects with < or = 0.1 optic nerve cup:disk ratio. The two groups were compared with respect to the history of recurrent herpes labialis, cigarette smoking status, hypertension, diabetes mellitus, cardiovascular disease, and cerebrovascular disease. The nonarteritic anterior ischemic optic neuropathy cases were comparable to controls with respect to cigarette smoking status, hypertension, diabetes mellitus, cardiovascular disease, and cerebrovascular disease status. Nonarteritic anterior ischemic optic neuropathy cases were significantly more likely to have a history of recurrent herpes labialis than controls. Herpes simplex virus as identified by recurrent herpes labialis plays a role in the development of nonarteritic anterior ischemic optic neuropathy. However, a casual relationship cannot be established.

Aged↗

Comparative antimicrobial activity of piperacillin-tazobactam tested against more than 5000 recent clinical isolates from five medical centers. A reevaluation after five years.

Piperacillin combined with tazobactam at a fixed concentration (4 micrograms/ml) and a ratio (8:1) was tested against 5,029 aerobic isolates and 447 fastidious organisms, including anaerobes. Among the Enterobacteriaceae, > 95% inhibition was shared only by imipenem (99.1% at < or = 4 micrograms/ml), and some newer cephalosporins (95.1% - 99.8% at < or = 8 micrograms/ml), and piperacillin-tazobactam (95.8% at < or = 16/4 micrograms/ml). Piperacillin-tazobactam was the most active agent tested against nonenteric Gram-negative bacilli (93.5% at < or = 8 micrograms/ml). Ampicillin-sulbactam was the most active agent against staphylococci (95.0% at < or = 8 micrograms/ml), followed by imipenem (91.8%), piperacillin-tazobactam (89.3% at < or = 8/4 micrograms/ml), and cefepime (86.2% at < or = 8 micrograms/ml). Against the enterococci, only ampicillin (93.0% at < or = 8 micrograms/ml) with or without sulbactam, piperacillin (91.0% at < or = 16 micrograms/ml) with or without tazobactam, and imipenem (91.0%) had acceptable activity. Piperacillin-tazobactam and imipenem were the most active drugs tested against all aerobic isolates, inhibiting 93.5% of isolates each. Piperacillin-tazobactam inhibited all fastidious isolates tested, including Haemophilus influenzae (MIC90, 0.094/4 micrograms/ml), Moraxella catarrhalis (MIC90, 0.064/4 micrograms/ml), Neisseira gonorrhoeae (MIC90, < or = 0.016/4 micrograms/ml), and Streptococcus pneumoniae (all MICs, < or = 4/4 micrograms/ml). Against the anaerobic isolates, the most broad-spectrum antimicrobial agents tested were imipenem (100.0%), piperacillin-tazobactam (99.5% at < or = 32/4 micrograms/ml), metronidazole (98.4% at < or = 8 micrograms/ml), and ticarcillin-clavulanic acid (95.1% at < or = 32/2 micrograms/ml). These results are nearly identical to a previous study involving the same five medical centers in 1989. Piperacillin-tazobactam appears to remain a highly effective beta-lactamase inhibitor combination with a wide empiric spectrum and potency in teaching hospitals.

Bacteria↗