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Biomedical subjects

G B Williams

Publications and source records attributed to G B Williams.

At least 19 recordsLinked to original sources

Development of a combined microPET-MR system.

As evidenced by the success of PET-CT, there are many benefits from combining imaging modalities into a single scanner. The combination of PET and MR offers potential advantages over PET-CT, including improved soft tissue contrast, access to the multiplicity of contrast mechanisms available to MR, simultaneous imaging and fast MR sequences for motion correction. In addition, PET-MR is more suitable than PET-CT for cancer screening due to the elimination of the radiation dose from CT. A key issue associated with combining PET and MR is the fact that the performance of the photomultiplier tubes (PMTs) used in conventional PET detectors is degraded in the magnetic field required for MR. Two approaches have been adopted to circumvent that issue: retention of conventional, magnetic field-sensitive PMT-based PET detectors by modification of other features of the MR or PET system, or the use of new, magnetic field-insensitive devices in the PET detectors including avalanche photo-diodes (APDs) and silicon photomultipliers (SiPMs). Taking the former approach, we are assembling a modified microPET Focus 120 within a gap in a novel, 1T superconducting magnet. The PMTs are located in a low magnetic field (approximately 30mT) through a combination of magnet design and the use of fiber optic 'bundles'. Two main features of the modified PET system have been tested, namely the effect of using long fiber optic bundles in the PET detector, and the impact of magnetic field upon the performance of the position sensitive PMTs. The design of a modified microPET-MR system for small animal imaging is completed, and assembly and testing is underway.

Animals↗

Diffusion tensor imaging in chronic head injury survivors: correlations with learning and memory indices.

Diffusion tensor imaging (DTI) provides a unique insight into the cellular integrity of the brain. While conventional magnetic resonance imaging underestimates the extent of pathology following closed head injury, diffusion-weighted imaging has been shown to more accurately delineate the extent of cerebral damage. There have only been a few case studies of DTI in chronic head injury survivors. This study used DTI to investigate changes in anisotropy and diffusivity in survivors of head injury at least 6 months after their injury. The relationship between cognition and diffusion abnormality was also investigated. The voxel-based analysis revealed significant bilateral decreases in anisotropy, in major white matter tracts and association fibers in the temporal, frontal, parietal and occipital lobes. Statistically significant increases in diffusivity were also found in widespread areas of the cortex. A significant positive correlation was found between diffusivity and impairment of learning and memory in the left posterior cingulate, left hippocampal formation and left temporal, frontal and occipital cortex. The common pattern of abnormality despite heterogeneous injury mechanism and lesion location in the group suggests that these cellular changes reflect secondary insults. The importance of diffusion abnormalities in head injury outcome is emphasized by the significant correlation between a learning and memory index and diffusivity in areas known to subserve this cognitive function.

Adolescent↗

Physiological thresholds for irreversible tissue damage in contusional regions following traumatic brain injury.

Cerebral ischaemia appears to be an important mechanism of secondary neuronal injury in traumatic brain injury (TBI) and is an important predictor of outcome. To date, the thresholds of cerebral blood flow (CBF) and cerebral oxygen utilization (CMRO(2)) for irreversible tissue damage used in TBI studies have been adopted from experimental and clinical ischaemic stroke studies. Identification of irreversibly damaged tissue in the acute phase following TBI could have considerable therapeutic and prognostic implications. However, it is questionable whether stroke thresholds are applicable to TBI. Therefore, the aim of this study was to determine physiological thresholds for the development of irreversible tissue damage in contusional and pericontusional regions in TBI, and to determine the ability of such thresholds to accurately differentiate irreversibly damaged tissue. This study involved 14 patients with structural abnormalities on late-stage MRI, all of whom had been studied with (15)O PET within 72 h of TBI. Lesion regions of interest (ROI) and non-lesion ROIs were constructed on late-stage MRIs and applied to co-registered PET maps of CBF, CMRO(2) and oxygen extraction fraction (OEF). From the entire population of voxels in non-lesion ROIs, we determined thresholds for the development of irreversible tissue damage as the lower limit of the 95% confidence interval for CBF, CMRO(2) and OEF. To test the ability of a physiological variable to differentiate lesion and non-lesion tissue, we constructed probability curves, demonstrating the ability of a physiological variable to predict lesion and non-lesion outcomes. The lower limits of the 95% confidence interval for CBF, CMRO(2) and OEF in non-lesion tissue were 15.0 ml/100 ml/min, 36.7 mumol/100 ml/min and 25.9% respectively. Voxels below these values were significantly more frequent in lesion tissue (all P < 0.005, Mann-Whitney U-test). However, a significant proportion of lesion voxels had values above these thresholds, so that definition of the full extent of irreversible tissue damage would not be possible based upon single physiological thresholds. We conclude that, in TBI, the threshold of CBF below which irreversible tissue damage consistently occurs differs from the classical CBF threshold for stroke (where similar methodology is used to define such thresholds). The CMRO(2) threshold is comparable to that reported in the stroke literature. At a voxel-based level, however (and in common with ischaemic stroke), the extent of irreversible tissue damage cannot be accurately predicted by early abnormalities of any single physiological variable.

Adolescent↗

Imaging of cerebral blood flow and metabolism in brain injury in the ICU.

The heterogeneity of the initial insult and subsequent pathophysiology has made both the study of human head injury and design of randomised controlled trials exceptionally difficult. The combination of multimodality bedside monitoring and functional brain imaging positron emission tomography (PET) and magnetic resonance (MR), incorporated within a Neurosciences Critical Care Unit, provides the resource required to study critically ill patients after brain injury from initial ictus through recovery from coma and rehabilitation to final outcome. Methods to define cerebral ischemia in the context of altered cerebral oxidative metabolism have been developed, traditional therapies for intracranial hypertension re-evaluated and bedside monitors cross-validated. New modelling and analytical approaches have been developed.

Animals↗

Initial experience with the advanced breast biopsy instrumentation system.

BACKGROUND: Advanced breast biopsy instrumentation is a recently designed alternative to large-core stereotactic and open needle localized breast biopsies. This minimally invasive technique uses digital stereotactic imaging to perform excisional biopsies of suspicious, nonpalpable mammographic lesions. The role of the ABBI system in the management of breast cancer has not yet been defined. METHODS: A retrospective review to evaluate the safety, accuracy, and cost effectiveness of the ABBI system as performed by a single surgeon on 107 patients from February 1, 1997 to January 31, 1998. We also discuss the use of the ABBI system as a therapeutic breast cancer technique. All patients had nonpalpable mammographic lesions. The mammographic abnormalities were either architectural distortion, microcalcifications, or stellate and nodular densities. RESULTS: Using the ABBI stereotactic unit, 110 breast biopsies were performed in 107 patients during a 12-month period. The mammographic abnormality was accurately localized and successfully biopsied in 99% (109 of 110) of the procedures as confirmed by specimen radiographs, stereotactic images, permanent pathologic sections, and 6-month follow-up mammograms. There were no intraoperative complications. Two patients developed postoperative wound hematomas and there was 1 postoperative wound infection. Six in situ cancers and 21 invasive cancers were diagnosed with the ABBI system. Two additional invasive cancers were diagnosed in patients with ductal carcinoma in situ at reexcision. Four patients with invasive ductal carcinoma and 1 patient with ductal carcinoma in situ had negative margins on their stereotactic biopsies and did not undergo reexcision by lumpectomy or mastectomy. Each of the 4 patients with invasive ductal carcinoma underwent axillary node dissections with postoperative radiation therapy and chemotherapy or tamoxifen. During the study period, the average hospital patient charge for a stereotactic breast biopsy was $2,377.75, and for an open excisional needle localized biopsy it was $3,028.00 (P <0.05). The stereotactic breast biopsy offered a total cost savings of $71,527.50 in our series of patients. CONCLUSION: Advanced breast biopsy instrumentation is a safe, accurate, and cost-effective method for performing breast biopsies. In addition, the ABBI system may be able to excise small in situ or invasive breast cancers.

Biopsy↗

Design of biplanar gradient coils for magnetic resonance imaging of the human torso and limbs.

A method is described for design of gradient coils of unconventional geometry for MRI that is based on the superpositions of magnetic fields arising from individual current elements calculated by the Biot-Savart Law. Use of an optimization method based on a genetic algorithm enables a wide diversity in the shapes of coil that can be modeled. To exemplify this a two axis, biplanar gradient set is presented; this geometry offers good access for rectangular objects whilst holding the coils closer to the region of interest than is possible for cylindrical configurations. The inner dimensions of the gradient set were 40.0 x 24.4 x 40.0 cm and the gradient efficiencies were 0.3 and 0.4 mT m(-1) A(-1) in the z- and y- directions respectively over a 15 cm diameter region. Correction of signals arising from regions for which gradient linearity was not optimized was successful for the monotonic region within the set; the largest cuboid from which the MR signal could be processed to produce an undistorted image is of dimensions 36.3 x 17.2 x 24.4 cm.

Algorithms↗

Spontaneous splenic rupture due to isolated splenic peliosis.

Peliosis is a rare condition in which blood-filled cysts occupy the parenchyma of solid organs. It most commonly involves the liver or liver and spleen, but isolated cases of splenic peliosis have been documented. Spontaneous splenic hemorrhage from splenic peliosis has been reported in the literature only 6 times. We present the seventh known case of spontaneous hemorrhage from a peliotic spleen in an otherwise healthy man.

Cysts↗

Multicenter evaluation of the MicroScan Rapid Gram-Negative Identification Type 3 Panel.

The accuracy and performance of the revised MicroScan Rapid Gram-Negative Identification Type 3 Panel (Dade MicroScan Inc., West Sacramento, Calif.) were examined in a multicenter evaluation. The revised panel database includes data for 119 taxa covering a total of 150 species, with data for 12 new species added. Testing was performed in three phases: the efficacy, challenge, and reproducibility testing phases. A total of 405 fresh and stock gram-negative isolates comprising 54 species were tested in the efficacy phase; 96.8% of these species were identified correctly in comparison to the identification obtained either with the API 20E system (bioMérieux Vitek, Hazelwood, Mo.) or by the conventional tube method. The number of correctly identified isolates in the challenge phase, including new species added to the database, was 221 of 247, or 89.5%, in comparison to the number correctly identified by the conventional tube method. A total of 465 isolates were examined for intra- and interlaboratory identification reproducibility and gave an agreement of 464 of 465, or 99.8%. The overall reproducibility of each individual identification test or substrate was 14,373 of 14,384, or 99.9%. The new Rapid Gram-Negative Identification Type 3 Panel gave accurate and highly reproducible results in this multiple-laboratory evaluation.

Evaluation Studies as Topic↗

Laparoscopic cholecystectomy in a community hospital: experience with 600 laparoscopic cholecystectomies.

We reviewed 600 patients who underwent laparoscopic cholecystectomy (LC) in a teaching community hospital from May 1990 to August 1992. The safety, efficacy, morbidity, and mortality of LC, as performed by one surgeon or under his direct supervision, were studied. Five hundred forty-eight patients (91.3%) were treated electively; 52 (8.7%) were admitted for acute cholecystitis (41) or gallstone pancreatitis (11). Mean operating time was 54 min, with a range of 20 to 145 min. Twenty-four (4%) patients required conversion to traditional (open) cholecystectomy. Operative cholangiograms were completed in 106 patients. These revealed choledocholithiasis in 7. Five hundred thirty-seven patients (89.5%) were discharged within 24 h and 564 (94%) within 48 h. The overall morbidity of 9.2% compared favorably with both open and laparoscopic series previously reported. Three patients (0.5%) had small lacerations of the anterior wall of the common duct. Two were recognized and repaired immediately. The third patient came for treatment on the fifth postoperative day and was stented by a T-tube. There was 1 death in this group--a myocardial infarction on postoperative day 4.

Cholecystectomy↗

Effect of smoking cessation upon circulatory responses to reactive hyperemia and cold pressor stress.

Local and sympathetic nervous system stress tests were administered prior to and following a 5-d smoking cessation program to determine the effects of short term smoking cessation upon peripheral circulation. Reactive hyperemia (RH) tests were performed on the forearm as a local dilatory stressor. Finger blood flow responses to cold pressor (CP) stresses were used to access stimulation of the sympathetic nervous system. Measures of heart rate and total forearm or finger blood flow, pulse volume and rate of blood delivery were obtained continuously during each stress test. Smoking cessation produced a significant decrease (0.01 < p < 0.05) in heart rate during both the RH and CP test sequences. Grouped mean peak forearm blood flow (Mean difference = 2.11 ml.100 ml-1.min-1; p < 0.05) and pulse volume (Mean difference = 0.04 ml.100 ml-1.pulse-1; p < 0.01) were both significantly greater following occlusion during the post-cessation RH tests than during the similar test before smoking cessation. Both finger pulse volume and rate of blood delivery were significantly greater (0.01 < p < 0.05) during the recovery portion of the post-cessation CP tests than during the same period of the pre-cessation tests. Thus, smoking cessation significantly altered both the locally mediated and central nervous system controlled responses to externally applied stressors.

Aged↗

Differences in outcome of transurethral resection of the prostate for benign prostatic hypertrophy between three diagnostic categories.

As part of a prospective cohort study of 388 men undergoing transurethral resection of the prostate (TURP) for benign prostatic hypertrophy, pre-operative factors and the outcome of surgery during the first post-operative year were compared between patients in whom their surgeon felt the principal reason for operating was chronic retention (37%), acute retention (with no chronic retention) (28%), or symptomatic prostatism (with no history of chronic or acute retention) (35%). Although in many respects the patients in the 3 diagnostic categories were similar, patients with chronic retention were more likely to be younger, of higher social class and to have worse general health. Patients with acute retention were more likely to present with a urinary tract infection and to have electrocardiographic abnormalities, and symptomatic patients presented with more severe urinary symptoms. Minor differences between the categories with regard to post-operative morbidity and mortality were not statistically significant at the 5% level. However, some significant differences did exist. Patients with acute retention were more likely to experience urinary and non-urinary infections and impotence after surgery, while symptomatic patients reported less improvement in their health status as regards pain and social isolation. These results suggest that the method of categorisation is clinically valid and a necessary distinction to make when auditing TURP.

Acute Disease↗

Mortality, morbidity and complications following transurethral resection of the prostate for benign prostatic hypertrophy.

A total of 388 men undergoing transurethral resection of the prostate for benign prostatic hypertrophy during 1988 entered a prospective cohort study designed to examine the outcome of surgery during postoperative year 1. Self-administered questionnaires were completed preoperatively, and at 3, 6 and 12 months postoperatively. The surgeons completed 1 questionnaire shortly after surgery and another questionnaire 3, 6 or 12 months later. The mortality rate during the 12 months of followup was 2.8% (11 deaths). The surgeons reported perioperative complications in 14% of the patients and immediate postoperative complications, excluding urinary tract infections, in 17%. During the first 3 months postoperatively 38% of the patients reported incontinence and 25% had a urinary tract infection. Between 6 and 12 months postoperatively only 12% of the patients were troubled by either condition. The postoperative prevalence of impotence (24%) did not alter during followup and was similar to that reported preoperatively (22%). Of the patients 74% reported feeling better and 78% experienced a decrease in the overall level of symptoms postoperatively. The improvement in symptom levels was greatest in those with the most severe preoperative symptoms, and obstructive symptoms were alleviated slightly more than irritative symptoms.

Adult↗

Rapid clonal growth measurements at the single-cell level: gel microdroplets and flow cytometry.

We describe a new, general method for rapidly measuring clonal growth of large numbers of individual members of a cell population. This method is based on microculture of individual colony-forming units in gel microdrops (GMDs; here agarose; 20 to 90 mu in diameter), which are sufficiently robust to be handled much like cells, and diffusionally transparent for molecules of interest. Flow cytometry provides rapid measurements of GMD-entrapped microcolonies, and permits subpopulation analysis. Here the method is demonstrated with mammalian, fungal and bacterial species. Additional results illustrate rapid determination of a drug-resistant subpopulation in a mixed species sample, and nutrient sensitivity for a murine hybridoma.

Animals↗

Urothelial grafts in mice.

Mouse bladder epithelium has been successfully transplanted to the bladders of syngeneic mice and has survived for at least twenty weeks. The fate of the transplanted tissue was followed using a fluorescein label. The recipient bladders were prepared by stripping the urothelium either by a surgical or a chemical method. The possibility of adopting a comparable technique for the treatment of early bladder cancer in man is discussed.

Animals↗

Rapid microbial detection and enumeration using gel microdroplets and colorimetric or fluorescence indicator systems.

A new micromethod employing gel microdroplets (GMDs) and optical measurements can be used for rapid detection and enumeration of viable microorganisms (J. C. Weaver, G. B. Williams, A. M. Klibanov, and A. L. Demain, Bio/Technology 6:1084-1089, 1988) and has several potential applications in clinical microbiology. This method involves entrapping microorganisms in GMDs (10 to 100 microns in diameter) which are surrounded by a hydrophobic (low dielectric) fluid, subsequently distinguishing occupied and unoccupied GMDs with colorimetric or fluorescence indicators, counting both occupied and unoccupied GMDs, and applying Poisson statistical analysis. Acid-producing microorganisms were used to compare colorimetric and fluorescence pH indicator systems. Fluorescence systems were generally superior, particularly for detection before microbial growth occurred. Although colorimetric detection was reasonably fast for fast-growing microorganisms, significantly longer times were needed for slow-growing microorganisms. We investigated the dependence of the detection time on microbial division time, GMD size, and buffering capacity of the medium within GMDs. It was found possible to use a single preparation of GMDs, containing a range of GMD sizes, to simultaneously provide a viable enumeration of growing and nongrowing (e.g., stressed) cells. This was possible because small GMDs responded rapidly to both growing and nongrowing cells, while large GMDs, although slower, responded much more rapidly to growing cells than to nongrowing cells. Separate analysis of small and large GMDs in the same preparation yielded two enumerations, one of nongrowing cells and the other of growing cells. GMDs can also be used with conventional light microscopy to detect and enumerate fast-growing acid-producing bacteria much more quickly than conventional plating methods.

Bacteria↗

Cholecystectomy in the elderly.

A series of 347 elderly patients undergoing cholecystectomy has been presented. The older a patient is at the time of cholecystectomy, the more likely it is for that patient to present with an acute biliary complication. The elderly tolerate biliary tract operations quite well, especially before acute complications of cholelithiasis occur. Early cholecystectomy can prevent the morbidity associated with the natural progression of cholelithiasis. Whether prophylactic cholecystectomy for asymptomatic cholelithiasis would be cost effective is an issue that can be resolved only when further data regarding the natural history and incidence of cholelithiasis in the elderly is known.

Age Factors↗

Primary squamous cell carcinoma of the colorectum: case report and literature review of a rare entity.

A case of primary squamous cell carcinoma of the rectum is presented. Although it is a rare condition, the diagnosis, treatment, and natural history of the disease are similar to that of adenocarcinoma of the colorectum. The patient in this report has done well to date with an abdominal perineal resection and early post-operative radiation. A review of the literature reveals that the precise etiology of this entity remains unknown.

Carcinoma, Squamous Cell↗