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Biomedical subjects

Michael D Williams

Publications and source records attributed to Michael D Williams.

At least 19 recordsLinked to original sources
PubMed2007

Sonographically guided core biopsy of a parotid mass.

OBJECTIVE: The purpose of this study was to evaluate the accuracy of sonographically guided core biopsy in the evaluation of parotid masses. SUBJECTS AND METHODS: Between 1998 and 2004, 135 patients consecutively presenting with a parotid mass were prospectively enrolled into this study. A single operator performed initial diagnostic sonography and then sonographically guided core biopsy using local anesthesia. Biopsy was performed with an 18- or 20-gauge needle and a spring-loaded biopsy gun with a mean of two passes per patient. Outcome measures were accuracy, sensitivity, specificity, and predictive values of sonographically guided core biopsy compared with the final pathologic diagnosis in the surgical group. In the nonsurgical group, final diagnosis was established on the basis of histologic findings after adequate core biopsy and clinical follow-up. RESULTS: All sonographically guided core biopsy specimens were considered satisfactory for histologic evaluation. Overall there were 71 benign tumors, 35 malignant tumors, and 29 miscellaneous, nonneoplastic lesions. In 76 (56%) of the 135 patients who underwent surgery, sonographically guided core biopsy and surgical histologic findings were correlated for 74 patients. In two cases sonographically guided core biopsy and surgical histologic findings did not correlate. In one case, the sonographically guided core biopsy finding was mucoepidermoid carcinoma, but the final diagnosis was squamous cell carcinoma. In the other case, the finding at sonographically guided core biopsy was squamous cell carcinoma, but the final diagnosis was mucoepidermoid carcinoma. The treatment of these patients was not affected. Fifty-nine (44%) of the 135 patients avoided surgery. In differentiation of benign from malignant disease, sonographically guided core biopsy had a sensitivity, specificity, and diagnostic accuracy of 100%. Sonographically guided core biopsy also had positive and negative predictive values of 100% in the diagnosis of malignancy. There were no significant complications of sonographically guided core biopsy. CONCLUSION: Sonographically guided core biopsy is a highly accurate technique for evaluation of parotid lesions and can be safely performed as an outpatient procedure. Sonographically guided core biopsy has potential advantages over fine-needle aspiration cytologic examination, particularly in the typing and grading of lymphoma and carcinoma and in improved differentiation of reactive nodal hyperplasia from lymphoma. The use of sonographically guided core biopsy may help reduce the need for surgical biopsy and facilitates prompt referral to the appropriate clinical team.

Adolescent↗
PubMed2006

Thoracolumbar fracture in blunt trauma: is clinical exam enough for awake patients?

BACKGROUND: Physical examination is widely used to screen trauma patients for thoracolumbar fracture (TLFx). Retrospective data suggests that patients with altered sensorium may not manifest symptoms after TLFx. This study was designed to prospectively test the sensitivity of physical examination for detection of TLFx in patients with altered mentation. METHODS: Prospective data collection in a large urban Level I trauma center from April 2002 to December 2003. During the study period, thoracolumbar radiography was performed on patients with signs or symptoms of TLFx, and also on patients with significant blunt trauma and any alteration in mentation, including drowsiness or apparent intoxication. All patients were classified as reliable if Glasgow coma score was >13 and the treating physician judged them capable of accurately reporting pain, and those who did not met both these conditions were deemed unreliable. Patients with normal mentation and no signs or symptoms were excluded. Injuries, mental status, symptoms, physical examination, and X-ray film results were recorded. RESULTS: There were 3,028 blunt trauma patients evaluated during the study period. Thoracolumbar radiography was performed on 537 patients. Of these, 442 patients were deemed reliable, and 166 had no signs or symptoms of TLFx. Of these asymptomatic patients, 10 were found to have TLFx. Of these 10 reliable patients with TLFx despite negative examination, none required surgery, but four required a brace. CONCLUSIONS: Thoracolumbar fractures are often clinically silent in blunt trauma patients with altered sensorium, even when they appear able to reliably report pain. X-ray screening of these patients is appropriate to prevent missed injury.

Adolescent↗
PubMed2006

Distinguishing between type 2B and pseudo-von Willebrand disease and its clinical importance.

Pseudo-von Willebrand disease (p-VWD) and type 2B von Willebrand disease (VWD) have similar phenotypic parameters and clinical symptoms, but different aetiologies. Fourteen individuals from five families with a historical diagnosis of type 2B VWD but with no mutation in the von Willebrand factor gene were re-investigated for the possibility of p-VWD, using platelet aggregation in the presence of cryoprecipitate. p-VWD was confirmed by targeted DNA sequencing of the glycoprotein Ibalpha gene, identifying a heterozygous Glycine 233 Valine substitution. This study suggests that p-VWD may be under diagnosed, and that platelet aggregation in the presence of cryoprecipitate is useful in differentiating this disorder from type 2B VWD.

DNA Mutational Analysis↗
PubMed2006

A review of inherited platelet disorders with guidelines for their management on behalf of the UKHCDO.

The inherited platelet disorders are an uncommon cause of symptomatic bleeding. They may be difficult to diagnose (and are likely to be under-diagnosed) and pose problems in management. This review discusses the inherited platelet disorders summarising the current state of the art with respect to investigation and diagnosis and suggests how to manage bleeding manifestations with particular attention to surgical interventions and the management of pregnancy.

Blood Coagulation Disorders, Inherited↗
PubMed2005

Requirement of VPS33B, a member of the Sec1/Munc18 protein family, in megakaryocyte and platelet alpha-granule biogenesis.

Bleeding problems are associated with defects in platelet alpha-granules, yet little is known about how these granules are formed and released. Mutations affecting VPS33B, a novel Sec1/Munc18 protein, have recently been linked to arthrogryposis, renal dysfunction, and cholestasis (ARC) syndrome. We have characterized platelets from patients with ARC syndrome and observed reduced aggregation with arachidonate and adenosine diphosphate (ADP). Structural abnormalities seen in ARC platelets included increased platelet size, a pale appearance in blood films, elevated numbers of delta-granules, and completely absent alpha-granules. Soluble and membrane-bound alpha-granule proteins were significantly decreased or undetectable in ARC platelets, suggesting that both the releasable protein pools and membrane components of alpha-granules were absent. The role of VPS33B in platelet granule biogenesis was evaluated by immunofluorescence microscopy in normal human megakaryocytes. VPS33B colocalized appreciably with markers of alpha-granules, moderately with late endosomes/lysosomes, minimally with delta-granules/lysosomes, and not with cis-Golgi complexes. VPS33B protein expression determined by immunoblotting confirmed the presence of VPS33B in control fibroblasts but not in ARC fibroblasts, and in normal megakaryocytes but not in platelets. We conclude that like other Sec1/Munc18 proteins, VPS33B is involved in intracellular vesicle trafficking, being essential for the development of platelet alpha-granules but not for granule secretion.

Arthrogryposis↗
PubMed2004

Antineoplastic agents. 380. Isolation and X-ray crystal structure determination of isoaaptamine from the Republic of Singapore Hymeniacidon sp. and conversion to the phosphate prodrug hystatin 1.

By use of bioassay (murine P388 lymphocytic leukemia cell line) guided isolation procedures, extracts of the Republic of Singapore marine sponge Hymeniacidon sp. were found to contain demethyloxyaaptamine (1) and aaptamine (3) as prominent cancer cell growth inhibitory constituents accompanied by the trace, albeit more active, component isoaaptamine (4). The isolation, X-ray structure elucidation, and antineoplastic and antimicrobial activities of isoaaptamine (4) have been summarized. Because of instability, isoaaptamine (4) was converted to a stable sodium phosphate prodrug designated hystatin 1 (7).

Animals↗
PubMed2004

Linear technique of laparoscopic Roux-en-Y gastric bypass.

The laparoscopic Roux-en-Y gastric bypass (LRYGB) is currently the most common procedure performed for treatment of morbid obesity in the United States. The technique reported in this chapter requires mastering of extra-corporeal and intra-corporeal laparoscopic suturing, but is safe, cost effective, and technically feasible. Use of the straight needle eliminates the challenge of proper needle orientation encountered with a curved needle. The linear technique is used to construct the gastrojejunostomy because it is time saving and relatively simple. An endoscopic ruler and bougie are used to ensure a consistent pouch size and alimentary limb length. This chaper demonstrates the use of preoperative preparation, and a meticulous surgical technique using the linear stapler, to perform a combined total of more than 1800 cases.

Anastomosis, Roux-en-Y↗
PubMed2003

Antineoplastic agents. 485. Isolation and structure of cribrostatin 6, a dark blue cancer cell growth inhibitor from the marine sponge Cribrochalina sp.

Cribrostatin 6, a dark blue cancer cell growth inhibiting (P388 ED(50) 0.3 microg/mL) constituent of the Republic of Maldives marine sponge Cribrochalina sp., has been assigned structure 3 on the basis of a combination of HRMS, high-field (500 MHz, HMBC, and GOESY experiments) (15)N, (1)H, and (13)C NMR, and X-ray crystal structure analyses. Cribrostatin 6 also was found to inhibit the growth of a number of pathogenic bacteria and fungi.

Animals↗
PubMed2003

Colon injury after blunt abdominal trauma: results of the EAST Multi-Institutional Hollow Viscus Injury Study.

BACKGROUND: Blunt injury to the colon is rare. Few studies of adequate size and design exist to allow clinically useful conclusions. The Eastern Association for the Surgery of Trauma Multi-institutional Hollow Viscus Injury (HVI) Study presents a unique opportunity to definitively study these injuries. METHODS: Patients with blunt HVI were identified from the registries of 95 trauma centers over 2 years (1998-1999). Patients with colon injuries (cases) were compared with blunt trauma patient undergoing a negative laparotomy (controls). Data were abstracted by chart review. RESULTS: Of the 227,972 patients represented, 2,632 (1.0%) had an HVI and 798 had a colonic/rectal injury (0.3%). Of patients diagnosed with HVI, 30.2% had a colon injury. No physical findings or imaging modalities were able to discriminate colonic injury. Logistic regression modeling yielded no clinically useful combination of findings that would reliably predict colonic injury. In patients undergoing laparotomy, presence of colon injury was associated with a higher risk of some complications but not mortality. Colon injury was associated with increased hospital (17.4 vs. 13.1, p < 0.001) and intensive care unit (9.7 vs. 6.9, p = 0.003) length of stay. Almost all colon patients (92.0%) underwent laparotomy within 24 hours of injury. CONCLUSION: Colonic injury after blunt trauma is rare and difficult to diagnose. No diagnostic test or combination of findings reliably excluded blunt colonic injury. Despite the inadequacy of current diagnostic tests, almost all patients with colonic injury were taken to the operating room within 24 hours. Even with relatively prompt surgery, patients with colon injury were at significantly higher risk for serious complications and increased length of stay. In contrast to small bowel perforation, delay in operative intervention appears to be less common but is still associated with serious morbidity.

Colon↗
PubMed2003

Diazonamide A and a synthetic structural analog: disruptive effects on mitosis and cellular microtubules and analysis of their interactions with tubulin.

The marine ascidian Diazona angulata was the source organism for the complex cytotoxic peptide diazonamide A. The molecular structure of this peptide was recently revised after synthesis of a biologically active analog of diazonamide A in which a single nitrogen atom was replaced by an oxygen atom. Diazonamide A causes cells to arrest in mitosis, and, after exposure to the drug, treated cells lose both interphase and spindle microtubules. Both diazonamide A and the oxygen analog are potent inhibitors of microtubule assembly, equivalent in activity to dolastatin 10 and therefore far more potent than dolastatin 15. This inhibition of microtubule assembly is accompanied by potent inhibition of tubulin-dependent GTP hydrolysis, also comparable with the effects observed with dolastatin 10. However, the remaining biochemical properties of diazonamide A and its analog differ markedly from those of dolastatin 10 and closely resemble the properties of dolastatin 15. Neither diazonamide A nor the analog inhibited the binding of [3H]vinblastine, [3H]dolastatin 10, or [8-14C]GTP to tubulin. Nor were they able to stabilize the colchicine binding activity of tubulin. These observations indicate either that diazonamide A and the analog have a unique binding site on tubulin differing from the vinca alkaloid and dolastatin 10 binding sites, or that diazonamide A and the analog bind weakly to unpolymerized tubulin but strongly to microtubule ends. If the latter is correct, diazonamide A and its oxygen analog should have uniquely potent inhibitory effects on the dynamic properties of microtubules.

Animals↗
PubMed2003

Unusual presentation of Lemierre's syndrome due to Fusobacterium nucleatum.

We report a case of Lemierre's syndrome due to Fusobacterium nucleatum in a previously healthy 19-year-old male. This is the first case report of Lemierre's syndrome due to thrombophlebitis of the external jugular vein. The patient had a rapid clinical response to anticoagulation and antibiotics, as supported by anecdotal evidence.

Adult↗
PubMed2003

Prospective randomized comparison of linear staplers during laparoscopic Roux-en-Y gastric bypass.

BACKGROUND: The development of laparoscopic linear staplers has enabled minimally invasive approaches to bariatric surgery, but there have been no comparison studies of the two current 6-row devices. We report our experience with a prospective randomized comparison of 6-row linear staplers during laparoscopic Roux-en-Y gastric bypass (LRYGBP). METHODS: From January to March 2003, 100 patients were randomly assigned to undergo LRYGBP with either an Endo-GIA Universal 6-row stapler (USSC) or the ETS-Flex 6-row stapler (Ethicon). Mean preoperative BMI was 49+/-8 for 50 Endo-GIA patients, and 49+/-7 for 50 ETS-Flex patients. Parameters measured included quantity of cartridges, handles, hemoclips, estimated blood loss, misfires, OR time, postoperative leaks and bleeds, and cost. RESULTS: Mean follow-up was 135 days (range 90- 180). The ETS-Flex group experienced significantly more misfires (28% vs 2%, P <.001), hemoclips applied (30+/-9 vs 21+/-7, P <.001), estimated blood loss (132+/-56 vs 100+/-32 ml, P <.001) and OR time (66+/-19 vs 58+/-13 mins, P <.02) compared with the Endo-GIA group respectively. There was one postoperative leak associated with the ETS-Flex group and two postoperative bleeds with the Endo-GIA group, which were not a significant differences. The Endo-GIA group averaged $319 more per case for staple cost. CONCLUSION: While the ETS-Flex stapler was less expensive, it was associated with more technical failures requiring surgeon intervention to reduce potential patient morbidity, compared with the Endo-GIA.

Adult↗
PubMed2002

Reconstruction challenge--combined use of pectoralis major and gastric pull-up flaps for massive naso-oropharyngeal/oesophageal defects.

Massive defects of the upper aerodigestive tract present a reconstructive challenge. We report a case in which a large defect of the naso-oropharyngeal and oesophagus was reconstructed with a combination of a gastric pull-up and a pectoralis major muscle flap. Postoperative function was good and survival was in excess of 16 months. The history of such reconstructions and possible alternative techniques are also discussed.

Carcinoma, Squamous Cell↗
PubMed2002

Identification, structural analysis and function of hyaluronan in developing fish larvae (leptocephali).

Hyaluronan (HA) has been identified as the principal glycosaminoglycan (CAG) in the highly hydrated, extracellular body matrix of the larval stage (leptocephalus) of seven species of true eels (Teleostei: Elopomorpha: Anguilliformes) and the ladyfish Elops saurus (Elopiformes), and was found as a minor GAG component in the bonefish Albula sp. (Albuliformes). Identification was based on: (1) HPLC separation of unsaturated disaccharides derived from chondroitinase ABC digests of whole-body GAG extracts; (2) 1H NMR analyses of native GAG polymers; and (3) degradation of GAG extracts by Streptomyces hyaluronan lyase. The unsaturated disaccharide 2-acetamido-2-deoxy-3-O-(beta-D-gluco-4-enepyranosyluronic acid)-D-glucose (DeltaDi-HA) accounted for 92.4-99.8% of the total disaccharides in chondroitinase digests. Trace amounts of unsaturated disaccharides of chondroitin sulfate were also present. Two-dimensional gCOSY spectra of the native HA polymer were similar for all species. Proton assignments for the HA disaccharide repeat (GlcAbeta1-3GlcNAcbeta1-4) in D(2)O, based on gCOSY, DQF-COSY and TOCSY analyses for the eel Ahlia egmontis, were concordant with published chemical shifts for HA oligosaccharides. In addition to its presumed role in maintaining the structural integrity and hydration of the gelatinous body of the leptocephalus, HA is postulated to function as a storage polysaccharide in those species in which it is the predominant GAG.

Animals↗
PubMed2002

Isolation and structure of pedilstatin from a republic of maldives Pedilanthus sp.

A new cancer cell growth inhibitor designated pedilstatin (1) was isolated from a Republic of Maldives Pedilanthus sp. The structure was determined to be 13-O-acetyl-12-O-[2'Z,4'E-octadienoyl]-4alpha-deoxyphorbol on the basis of high-resolution mass spectral and 2D NMR assignments. Pedilstatin was found to significantly inhibit growth of the P388 lymphocytic leukemia cell line with an ED(50) of 0.28 microg/mL, to afford, at concentrations of 2-5 microM, protection (to 80%) of human-derived lymphoblastoid CEM-SS cells from infection and cell-killing by HIV-1, and to show inhibition of protein kinase C with a K(i) of 620 +/- 20 nM.

Animals↗
PubMed2002

The investigation and management of neonatal haemostasis and thrombosis.

These guidelines address developmental aspects of neonatal haemostasis and thrombosis, the laboratory investigation of the neonate, and the diagnosis and clinical management of haemostatic and thrombotic conditions occurring in this period (defined as the first 4 weeks of life following birth). Relevant scientific papers were identified by a systematic literature review from Medline 1975-2000 using index terms which incorporated the various component subjects of these guidelines. Further publications were obtained from the references cited and from reviews known to the members of the working party and to the Haemostasis and Thrombosis Task Force. Evidence and graded recommendations presented in these guidelines are in accordance with the US Agency for Health Care Policy and Research, as described in the Appendix. It will be noted that there is a lack of a strong evidence base for many of the recommendations suggested, as the appropriate clinical and laboratory trials have not been and perhaps never will be undertaken in neonates. Most of the recommendations are therefore of Grade C evidence levels IV: higher levels are mentioned specifically throughout the document when relevant.

Blood Coagulation Disorders↗