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Biomedical subjects

S J Gordon

Publications and source records attributed to S J Gordon.

At least 19 recordsLinked to original sources
PubMed2001

Use of the CEEA stapler to avoid ultra-low segmental resection of a full-thickness rectal endometriotic nodule.

A woman with a history of numerous surgical episodes for treatment of aggressive endometriosis experienced rectal symptoms. She was prepared for the possibility of laparotomy with or without colostomy to relieve her symptoms. After extensive laparoscopic dissection of the rectovaginal septum, a circular stapling device (Premium Plus CEEA; Autosuture, Melbourne, Victoria, Australia) was used to excise completely an anterior rectal lesion that otherwise would have resulted in ultra-low rectal resection and anastomosis. Morbidity associated with the latter procedure was avoided; the patient was discharged within 72 hours and experienced no early or late complications. Postoperative barium enema was obviated by rapid return to normal bowel habits and complete resolution of dyschezia and dyspareunia.

Adult↗
PubMed1999

Impaired transition state complementarity in the hydrolysis of O-arylphosphorothioates by protein-tyrosine phosphatases.

The hydrolysis of O-arylphosphorothioates by protein-tyrosine phosphatases (PTPases) was studied with the aim of providing a mechanistic framework for the reactions of this important class of substrate analogues. O-arylphosphorothioates are hydrolyzed 2 to 3 orders of magnitude slower than O-aryl phosphates by PTPases. This is in contrast to the solution reaction where phosphorothioates display 10-60-fold higher reactivity than the corresponding oxygen analogues. Kinetic analyses suggest that PTPases utilize the same active site and similar kinetic and chemical mechanisms for the hydrolysis of O-arylphosphorothioates and O-aryl phosphates. Thio substitution has no effect on the affinity of substrate or product for the PTPases. Bronsted analyses suggest that like the PTPase-catalyzed phosphoryl transfer reaction the transition state for the PTPase-catalyzed thiophosphoryl transfer is highly dissociative, similar to that of the corresponding solution reaction. The side chain of the active-site Arg residue forms a bidentate hydrogen bond with two of the terminal phosphate oxygens in the ground state and two of the equatorial oxygens in a transition state analog complex with vanadate [Denu et al. (1996) Proc. Natl. Acad. Sci. USA 93, 2493-2498; Zhang, M. et al. (1997) Biochemistry 36, 15-23; Pannifer et al. (1998) J. Biol. Chem. 273, 10454-10462]. Replacement of the active-site Arg409 in the Yersinia PTPase by a Lys reduces the thio effect by 54-fold, consistent with direct interaction and demonstrating strong energetic coupling between Arg409 and the phosphoryl oxygens in the transition state. These results suggest that the large thio effect observed in the PTPase reaction is the result of inability to achieve precise transition state complementarity in the enzyme active site with the larger sulfur substitution.

Binding Sites↗
PubMed1999

The incidence and management of failed Pipelle sampling in a general outpatient clinic.

A prospective audit was performed on 100 consecutive patients who underwent Pipelle endometrial sampling in a general outpatient clinic setting. The indications for sampling were abnormal menstrual bleeding (AMB, 65), intermenstrual or postcoital bleeding (IMB/PCB, 7), postmenopausal bleeding (PMB, 28). An insufficient sample was obtained in 33 women: (AMB 14, 21.5%); IMB/PCB, (0); PMB 19,68%). In 3 women the Pipelle was unable to be introduced through the cervix; in the remainder an insufficient sample for histological diagnosis was obtained. Registrars and resident doctors were more likely to sample insufficiently. In the AMB group all but 1 woman with an insufficient sample had further investigations or treatment but 7 of 19 (37%) of PMB patients had no further investigations. Where definitive histology was available, endometrial polyps or submucous fibroids were found in half of the cases with an inadequate Pipelle sample. Pipelle sampling detected only 1 of the 2 cases of endometrial cancer in this study.

Adult↗
PubMed1998

Molecular basis for substrate specificity of protein-tyrosine phosphatase 1B.

Protein-tyrosine phosphatases can exhibit stringent substrate specificity in vivo, although the molecular basis for this is not well understood. The three-dimensional structure of the catalytically inactive protein-tyrosine phosphate 1B (PTP1B)/C215S complexed with an optimal substrate, DADEpYL-NH2, reveals specific interactions between amino acid residues in the substrate and PTP1B. The goal of this work is to rigorously evaluate the functional significance of Tyr46, Arg47, Asp48, Phe182, and Gln262 in substrate binding and catalysis, using site-directed mutagenesis. Combined with structural information, kinetic analysis of the wild type and mutant PTP1B using p-nitrophenyl phosphate and phosphotyrosine-containing peptides has yielded further insight into PTP1B residues, which recognize general features, as well as specific properties, in peptide substrates. In addition, the kinetic results suggest roles of these residues in E-P hydrolysis, which are not obvious from the structure of PTP1B/peptide complex. Thus, Tyr46 and Asp48 recognize common features of peptide substrates and are important for peptide substrate binding and/or E-P formation. Arg47 acts as a determinant of substrate specificity and is responsible for the modest preference of PTP1B for acidic residues NH2-terminal to phosphotyrosine. Phe182 and the invariant Gln262 are not only important for substrate binding and/or E-P formation but also important for the E-P hydrolysis step.

Amino Acid Sequence↗
PubMed1992

Toxicity of single-day high-dose vincristine, melphalan, etoposide and carboplatin consolidation with autologous bone marrow rescue in advanced neuroblastoma.

16 unselected patients with advanced neuroblastoma were given high-dose consolidation chemotherapy with vincristine, melphalan, etoposide and carboplatin over 5 h followed by autologous bone marrow rescue. 3 patients died from treatment-related toxicity, 2 from disease, 1 is alive with disease and 10 are alive and disease-free a median of 12.5 months (range 2-38 months) after bone marrow rescue. All had bone marrow toxicity, most mucositis and 6 had seizures. Renal failure was unexpectedly severe. In the last 3 patients, administration of carboplatin was delayed by 18 h in an attempt to reduce renal damage. The results show that this regimen produces significant morbidity and has a high mortality. Although the overall outcome is encouraging, too few patients have been studied to gauge its efficacy. Whether such aggressive consolidation is necessary in heavily pretreated children with neuroblastoma remains unknown.

Adolescent↗
PubMed1991

Successful shock-wave lithotripsy of bile duct stones using ultrasound guidance.

Eighteen patients with 41 gallstones in the common bile duct, common hepatic, cystic, and intrahepatic ducts underwent shock-wave lithotripsy using the electrohydraulic Sonolith 3000 lithotripter. Lithotripsy was performed using ultrasound guidance alone under intravenous analgesia/sedation. All patients previously had failed stone extraction via retrograde endoscopy, T-tube, or cholecystostomy. Lithotripsy was performed according to an FDA-approved protocol allowing a maximum of two 2500 shock-wave treatments at a 48 hr interval. Following the final lithotripsy or cholangiographic evidence of stone fragmentation, residual fragments were removed via endoscopic or percutaneous route within 24-72 hr. Ultrasound localization of gallstones was aided by continuous infusion of the common bile duct with saline solution. In 15 of the 18 patients, complete fragmentation of the stones was accomplished, two had minimal fragmentation, and one with an encysted stone had no fracturing. No serious complications were encountered. Overall nonsurgical stone-free success rate was 17 of 18 patients, indicating biliary duct stones can be successfully treated using an ultrasound-guided lithotripter and intravenous sedation alone.

Aged↗
PubMed1991

Transhepatic laser lithotripsy of choledocholithiasis: initial clinical experience.

Three patients with symptomatic intra- and extrahepatic choledocholithiasis who were not good candidates for retrograde endoscopy, surgery, or extracorporeal shock wave lithotripsy (ESWL) were treated successfully with endoscopically guided tunable dye laser lithotripsy via a 12-F transhepatic sheath. There were no complications secondary to the use of the laser. On the basis of this initial experience, transhepatic laser lithotripsy is a technically feasible and safe alternative when choledocholithiasis cannot be managed with retrograde endoscopy, ESWL, or surgery. Its role in the management of choledocholithiasis relative to other transhepatic techniques remains to be determined.

Adult↗
PubMed1991

Mechanism of disc rupture. A preliminary report.

Lumbar intervertebral disc herniation is thought to be related to senescent changes in the nucleus pulposus except in rare instances of trauma. This investigation provides the first in vitro model of disc prolapse that reliably ruptures discs under physiologically reasonable stress. Fourteen vertebral motion segments with intact posterior elements were loaded repetitively at 1.5 Hz in a combination of flexion (7 degrees), rotation (less than 3 degrees), and compression (1,334 N) for an average of 6.9 hours (range, 3.0-13.0 hours) in a materials testing machine. Loading was terminated when reaction force leveled off for more than 1 hour. Ten discs failed through annular protrusions, and four failed by nuclear extrusion through annular tears, supporting the hypothesis that intervertebral disc prolapse is peripheral in origin. The annulus fibrosus is the site of primary pathologic change.

Humans↗
PubMed1991

Assessment of cardiac function by M-mode echocardiography in selenium-deficient phenylketonuric children.

Selenium (Se) deficiency is associated with cardiac and skeletal muscle dysfunction. Twenty well children aged 2-16 years (10 male) attending the Phenylketonuria (PKU) Clinic at the Royal Children's Hospital, Brisbane, had low Se levels (mean 0.29 +/- 0.02 s.e.m. mumol/L; normal range 0.56-1.16 mumol/L). Their myocardial function was assessed at rest and after exercise provocation by M-mode echocardiography in order to exclude occult left ventricular dysfunction. At rest, fractional shortening (FS) was normal (mean 38.1 +/- 1.1 s.e.m. %, n = 20). After exercise, FS increased significantly (P less than 0.001) from 37.6 +/- 1.4% to 44.3 +/- 1.2%, n = 12). This was associated with a significant rise (P less than 0.001) in heart rate (HR) from 77.3 +/- 3.1 beats/min to 125.8 +/- 5.2 beats/min (n = 12). The normal resting FS and normal increase in FS and HR with exercise is evidence against significant cardiac impairment in this group of Se-deficient children.

Adolescent↗
PubMed1986

Endosonographic evaluation of mural abnormalities of the upper gastrointestinal tract.

An end-viewing fiberoptic gastroscope was modified to incorporate a high-resolution linear array real-time ultrasound transducer 7 cm proximal to the flexible tip of the instrument. This endoscope was used to evaluate 20 patients suspected of having mural disease of the upper gastrointestinal tract and five normal subjects. The endosonographic examination defined esophageal, stomach, and duodenal wall thickness in normal subjects. In patients with pathological findings, both diffuse and acoustically focal lesions were demonstrated, and the extent of these lesions were outlined. With focal masses, endosonographic findings also demonstrated echogenic differences between various submucosal tumors reflecting their differing etiology. The extent of invasion and adenopathy were identified in a patient with gastric carcinoma. With diffuse lesions, the depth of involvement could be outlined sonographically, but etiologic diagnosis depended on biopsy. Extrinsic masses with secondary invasion of the wall of the upper gastrointestinal tract were defined in six patients. It is suggested that endosonography may prove to be a useful technique for evaluation of mural, invasive extramural, and diffuse lesions of the upper gastrointestinal tract.

Adult↗