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Biomedical subjects

M L Freeman

Publications and source records attributed to M L Freeman.

At least 55 records · Page 3Linked to original sources

Biliary-shunt fistula following transjugular intrahepatic portosystemic shunt placement.

Sepsis following the placement of a transjugular intrahepatic portosystemic shunt (TIPS) has been reported in up to 10% of cases. This report describes an unusual case of polymicrobial gram-negative sepsis after placement of TIPS associated with a cholangiographically documented fistulous connection between the biliary tree and shunt. The patient was treated with temporary biliary stent placement, endoscopic sphincterotomy, and broad-spectrum antibiotics with rapid closure of the fistula and resolution of sepsis. In the absence of hemobilia, it is hypothesized that flow through the fistula allowed bilious contamination of the systemic circulation and subsequent inoculation with enteric flora. The prevalence of biliary-vascular fistula after placement of TIPS is unknown. It may be a previously unsuspected source of sepsis after placement of TIPS and is likely to be overlooked unless endoscopic retrograde cholangiopancreatography is performed.

Biliary Fistula↗

Kinaesthetic sensitivity of adolescent male and female athletes and non-athletes.

Comparisons were made between nineteen ballet dancers/gymnasts, twenty basketballers, and twenty non-athletes (mean age 16.19 years) in terms of their kinaesthetic sensitivity to passive upper arm movement. The measurement instrument used was the Kinaesthetic Sensitivity Test developed by Laszlo and Bairstow (1985a). The results showed that kinaesthetic sensitivity did not differ across groups, although there was evidence of some difference between males and females. These results are in conflict with previous studies (Bairstow & Laszlo, 1981; Laszlo & Bairstow, 1980). The data suggest the need for research on kinaesthetic sensitivity to provide normative adolescent data, to further examine sex differences, and to investigate differences between athletes of differing levels.

Adolescent↗

Characterization of a signal generated by oxidation of protein thiols that activates the heat shock transcription factor.

The diazenecarbonyl derivative, diamide, was used to produce nonnative protein disulfides in Chinese hamster ovary cells in order to characterize the events that occur during thiol oxidation-induced denaturation that trigger induction of Hsp 70. We limit the term protein denaturation to a process involving a conformational rearrangement by which the ordered native structure of a protein changes to a more disordered structure. Protein thiol oxidation resulted in immediate destabilization of proteins, as assessed by differential scanning calorimetry (DSC). The DSC profile indicated both a decrease in the onset temperature for detection of denaturation and destabilization of a class of proteins with an average transition temperature (Tm) of 60 degrees C. Concomitant with destabilization was an increase in proteins associated with isolated nuclei. Thiol oxidation also induced heat shock transcription factor (HSF) binding activity, however, this was nearly undetectable immediately following diamide treatment: maximum activation occurred 3 hr following exposure. In contrast, heat shock denatured thermolabile proteins which exhibited a Tm of < or = 48 degrees C. Heat shock also resulted in a rapid increase in proteins associated with isolated nuclei and produced immediate and maximum activation of HSF binding. The accumulation of Hsp and Hsc 70 mRNA following thiol oxidation reflected the delay in HSF binding. Acquisition of HSF binding activity occurred immediately if diamide-treated cells were subsequently exposed to a heat shock, indicating that HSF was not inactivated by the diamide treatment. Ostensibly, the cellular system for detecting denatured/abnormal proteins failed to immediately recognize the signal generated by thiol oxidation. These results suggest that at least two processes are involved in the induction of Hsp 70 by nonnative disulfide bond formation: destabilization of protein structure resulting in denaturation and recognition of denatured protein.

Animals↗

Omeprazole use at an urban county teaching hospital.

To determine the appropriateness of use of omeprazole, all outpatient prescriptions over one year from a single county hospital pharmacy were analyzed. Appropriateness of omeprazole use was assessed by literature review and expert opinion. Two hundred twenty-one prescriptions were evaluated; 112 (56%) were inappropriate. Women received more inappropriate prescriptions (61% vs 44%, p = 0.01) and received endoscopy less frequently (52% vs 71%, p < 0.02) than did men. When age, gender, and prescribing clinic were examined as predictors of inappropriate use, only gender was significant (OR = 2.01, 95% CI = 1.52-2.66). This study, from a single institution, showed a high rate of inappropriate omeprazole use.

Drug Utilization Review↗

Training endoscopists to recognize the stigmata of hemorrhage in bleeding ulcers.

Correctly assessing the stigmata of recent hemorrhage is critical to providing appropriate endoscopic and medical management in patients with bleeding ulcers. However, the task of training endoscopists to recognize stigmata in ulcers is particularly difficult, for a number of reasons. First, the source of bleeding must be located, and this may be difficult when blood is present or the patient is unstable; second, the ulcer base must be completely examined, sometimes requiring target irrigation or manipulation of the surrounding folds with a device; third, the presence or absence of stigmata must be recognized; and finally, the stigma must be accurately identified. A major problem is that even expert endoscopists and investigators in the field of hemostasis have not achieved a consensus on definitions of stigmata. Nonetheless, the available data suggest that endoscopists can be trained to identify stigmata with reasonable consistency.

Endoscopy, Gastrointestinal↗

Genes regulating glutathione concentrations in X-ray-transformed rat embryo fibroblasts: changes in gamma-glutamylcysteine synthetase and gamma-glutamyltranspeptidase expression.

The concentration of glutathione (GSH) and the expressions of gamma-glutamylcysteine synthetase and gamma-glutamyltranspeptidase (GGT) were assessed in rat embryo fibroblasts (REF) displaying various stages of X-ray-induced transformation. A secondary culture of REF cells was irradiated, and a normal-immortalized cell line (X-REF-23) was isolated. Chronic exposure of X-REF-23 cells to 12-O-tetradecanoyl-phorbol-13-acetate (TPA) yielded cells (X-REF-23-TP) capable of benign tumor formation in nude mice. These cells exhibited GSH concentrations and gamma-glutamylcysteine synthetase heavy subunit mRNA levels that were approximately 50% less than those measured in X-REF-23 cells. Neither X-REF-23 nor X-REF-23-TP cells exhibited detectable GGT mRNA or activity. Administration of 3 Gy of X-rays followed by chronic TPA treatment yielded cells (X-REF-23-TPX) capable of malignant tumor formation in nude mice. These cells expressed GGT mRNA and Concanavalin-A minus GGT activity. One TPX clone (X-REF-23-TPX.1) was chosen for further characterization. Northern blotting of X-REF-23-TPX.1 cells indicated that gamma-glutamylcysteine synthetase heavy subunit mRNA levels were similar to those of X-REF-TP cells. X-REF-23-TPX.1 cells contained nearly the same amount of GSH as X-REF-23 cells. However, the ability of diethylmaleate (DEM) to deplete GSH was diminished in X-REF-23-TPX.1 cells compared with X-REF-23 cells. Furthermore, exposure of X-REF-23-TPX.1 cells to DEM stimulated GSH resynthesis such that the GSH concentration exceeded control values during exposure. The resynthesis of GSH during a DEM exposure was found to be dependent upon the expression of GGT, as demonstrated by inhibition with AT-125. These experiments indicate that ionizing radiation can lead to elevated constitutive expression of GGT in transformed REF cells and that expression of GGT activity was responsible for the increased rate of GSH repletion observed in X-REF-23-TPX.1 cells.

Animals↗

Major hemorrhage from endoscopic sphincterotomy: risk factor analysis.

We carried out a retrospective cohort study on all patients undergoing sphincterotomy at our institution over a 4-year period. Major hemorrhage occurred in 10 of 189 patients (5.3%). Onset was usually delayed (mean, 3.0 days; range, 0-9 days). Six potential risk factors for postsphincterotomy hemorrhage were assessed by univariate and multivariate analysis. Three factors predicted postsphincterotomy hemorrhage: hemodialysis (relative risk, 8.4; 95% confidence interval, CI, 2.7-26.4), a prothrombin time prolonged at least 2 s above control (relative risk, 7.8; 95% CI, 2.4-25.6), and endoscopically observed bleeding at the time of sphincterotomy (relative risk, 5.9; 95% CI, 1.7-20.1). Features not independently associated with hemorrhage were sphincter of Oddi dysfunction, aspirin or nonsteroidal anti-inflammatory drug (NSAID) use within 1 week prior to sphincterotomy, and sphincterotomy length. When differentiated from endoscopically observed bleeding, clinically significant hemorrhage was usually a delayed complication, primarily in patients with hemostatic defects.

Age Distribution↗

Sedation and monitoring for gastrointestinal endoscopy.

Delivery of safe but effective sedation can be a challenge for the endoscopist. Complications include respiratory depression, aspiration and cardiac arrhythmias, and the cardiopulmonary mortality of endoscopy may exceed that of general anesthesia. To administer sedation properly, it is necessary for endoscopists to understand the definitions and hazards of conscious versus deep sedation, the role of electronic monitoring devices such as pulse oximetry, and the pharmacology of the agonist and reversal agents used. They must develop a systematic approach to sedation in conjunction with well-trained gastrointestinal assistants and know the limitations of their abilities. These topics are reviewed in this article, and a general approach to sedation is presented.

Anesthesia, General↗

Objective evaluation of endoscopy skills during training.

OBJECTIVE: To evaluate the number of supervised gastrointestinal endoscopic procedures required to achieve initial competency using a simple objective grading system. DESIGN: Prospective, cross-sectional study. SETTING: A gastroenterology and surgical training program at a large, university-affiliated county hospital. PARTICIPANTS: Seven gastroenterology fellows and five fourth-year surgery residents. INTERVENTIONS: Trainees were graded postprocedure using a microcomputer program. Grading criteria for esophagogastroduodenoscopy included entering the esophagus (esophageal intubation), traversing the pylorus into the duodenum, and recognizing whether the upper gastrointestinal tract was abnormal. Criteria for colonoscopy were traversing the splenic flexure, intubating the cecum, and recognizing whether the colon was abnormal. RESULTS: When presented with a case mix representative of practice, esophageal intubation did not reach 90% until more than 100 procedures had been done. Cecal intubation remained at only 84% after 100 procedures. CONCLUSIONS: More than 100 supervised upper gastrointestinal endoscopies or colonoscopies are necessary to achieve technical competence in gastrointestinal endoscopy.

Clinical Competence↗

Carbon dioxide retention and oxygen desaturation during gastrointestinal endoscopy.

BACKGROUND: Pulse oximetry measures arterial oxygen saturation (SpO2), not hypoventilation, which is directly reflected by increases in carbon dioxide tension. METHODS: In the present study, transcutaneous carbon dioxide tension (PtcCO2) and SpO2 were measured during 101 endoscopic procedures selected for long duration or comorbid illnesses, and relationships between hypercapnia and hypoxemia were evaluated. Nasal oxygen was administered only for sustained desaturation (SpO2 < 90%). RESULTS: Mean peak increase in PtcCO2 was significantly higher in patients requiring oxygen for sustained desaturation (16.3 mm Hg; range, 4-52) than in patients breathing room air who had transient or no desaturation (10.2 mm Hg [range, 3-19] and 5.1 mm Hg [range, 0-15]). If nasal oxygen corrected desaturation, even transient recurrence of desaturation indicated worsening CO2 retention, which preceded respiratory arrest in one patient. Independent predictors of hypercapnia were fentanyl and midazolam doses, oxygen requirement, and dementia. CONCLUSIONS: Severe hypoventilation may occur during endoscopy, undetected by clinical observation or pulse oximetry, but only in sedated patients who require supplemental oxygen to maintain SpO2 above 90%. After oxygen supplementation corrects desaturation, recurrence of desaturation implies severe hypoventilation and warrants limitation of further sedation.

Adult↗

Gamma irradiation increases hsp-70 in Chinese hamster ovary cells.

The induction of hsp-70 by gamma irradiation was studied in Chinese hamster ovary (CHO) cells. Synthesis of hsp-70 was assessed by SDS-PAGE of radiolabeled proteins while levels of hsp-70 mRNA were estimated by Northern blot analysis of total RNA. SDS-PAGE analysis indicated that the synthesis of hsp-70 was enhanced in cells exposed to 400 or 1000 Gy. Northern blot analysis of RNA from cells exposed to 1000 Gy indicated a rapid increase in mRNA capable of hybridizing to an hsp-70 oligonucleotide probe. These experiments represent the first report demonstrating that ionizing radiation can increase hsp-70 mRNA.

Animals↗

Synthesis of hsp-70 is enhanced in glutathione-depleted Hep G2 cells.

The question of whether depletion of glutathione (GSH) could affect the synthesis of stress proteins was investigated in Hep G2 cells. Cells were exposed to BSO/DEM at 37 degrees C to deplete glutathione. When 95% of the glutathione was depleted cells were washed, and BSO was added to cells previously exposed to BSO/DEM; then the cells were incubated at 37, 38.5, or 39 degrees C for 4 h. Two-dimensional PAGE analysis of GSH-depleted cells incubated at 37 degrees C indicated increased synthesis of heme oxygenase and a polypeptide tentatively identified as hsp-70B'. Depletion of GSH did not affect the cellular concentration of hsp-70 as assessed by Western immunoblotting, yet Northern blot analysis indicated that hsp-70 mRNA was increased in GSH-depleted cells. Incubation of GSH-replete cells at 38.5 degrees C did not appear to enhance the amount of hsp-70 mRNA or the relative rate of hsp-70 synthesis. In contrast, incubation of GSH-depleted cells at 38.5 degrees C elevated steady-state hsp-70 mRNA levels and the rate of hsp-70 synthesis relative to total protein synthesis. Depletion of GSH also increased the relative rate of hsp-70 synthesis at 39 degrees C. These results suggest that the synthesis of stress proteins can be affected by glutathione concentrations.

Buthionine Sulfoximine↗

Results of a multicenter trial using a mechanical lithotripter for the treatment of large bile duct stones.

A prospective, uncontrolled trial of the use of a prototype mechanical lithotripter was performed in 116 patients at nine centers. Standard endoscopic approaches had failed to remove all stones, primarily because of large size (80% of patients). For 92% of patients, common bile duct stones were successfully captured and fragmented following the use of this lithotripter. The frequency of pancreatitis and hemorrhage was no greater than with standard endoscopic retrograde sphincterotomy, and complications unique to lithotripter use were not noted. For endoscopists skilled in therapeutic duodenoscopy, this modality should be considered in management of common bile duct stones refractory to standard techniques.

Equipment Design↗