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Biomedical subjects

T McDermott

Publications and source records attributed to T McDermott.

17 recordsLinked to original sources

An audit of 2273 ureteroscopies--a focus on intra-operative complications to justify proactive management of ureteric calculi.

BACKGROUND: At the national Stone Centre we have adopted a proactive management approach involving early ureteroscopy for ureteric calculi. As the efficacy of ureteroscopy is known this study focuses on the low intra-operative complication rate as justification for a proactive management protocol. PATIENTS AND METHODS: A retrospective study (1987-1997) identified 1936 patients undergoing 2273 ureteroscopies. A database was created from inpatient hospital records. The male to female ratio was 3 to 1, age range was 25 to 84 years. RESULTS: Twenty-three patients (1%) had an intra-operative complication during ureteroscopy. Immediate ureteric JJ stenting was performed in 16 cases with ureteric injury. Two cases underwent percutaneous drainage and delayed antegrade ureteric stenting, ureteroscopy was terminated because of poor visibility. Five patients (0.22%) underwent open surgery for: ureteric perforation (n = 2); Dormia basket ureteric avulsion (n = 1); impacted Dormia basket and stone (n = 1); and impacted balloon dilator and stone (n = l). Ureteroscopic complications were not related to the level of ureteric calculus. CONCLUSION: A protocol of proactive management of ureteric calculi facilitates rapid turnover of large patient numbers. This approach is supported by the low intra-operative complication rate, most of which can be managed by further endoscopic procedures. In the event of corrective open surgery a favourable outcome has resulted.

Adult↗

Technical report. Intra-operative ultrasound-guided needle localization for impalpable testicular lesions.

AIMS: To describe a new technique of intra-operative ultrasound-guided needle localization of impalpable intratesticular lesions. MATERIALS AND METHODS: Three patients with impalpable testicular lesions identified on ultrasound underwent needle localization under ultrasound guidance. The procedure was performed in the operating theatre under general anaesthetic using a 7.5-8 MHz linear array probe and a portable ultrasound machine. Under direct guidance, a 21 G needle was placed through the centre of the lesion allowing resection and immediate frozen section analysis. RESULTS: In two patients malignancy was confirmed and an orchidectomy was performed. In one patient a benign lesion was detected obviating the need for orchidectomy. CONCLUSION: Patients presenting with impalpable testicular lesions can pose a diagnostic dilemma and orchidectomy is often performed. We describe an ultrasound-guided intra-operative localization technique enabling direct pathological examination so surgical approach can be re-evaluated in the presence of a benign lesion. This is particularly important in the case of a solitary testicle in order to preserve testicular function.

Adult↗

Physiological difference during ethanol fermentation between calcium alginate-immobilized Candida tropicalis and Saccharomyces cerevisiae.

Calcium alginate-immobilized Candida tropicalis and Saccharomyces cerevisiae are compared for glucose fermentation. Immobilized C. tropicalis cells showed a slight morphological alteration during ethanol production at 40 degrees C, but their fermentation capacity was reduced by 25%. Under immobilization conditions, the two species demonstrated two different mathematical patterns when the relationship between growth rate, respiration rate, and ethanol tolerance was assessed. The interspecific difference in behavior of immobilized yeast cells is mainly due to their natural metabolic preference. The production of CO(2) by calcium alginate-immobilized C. tropicalis, as well as the lower supply of oxygen to the cells, are the major factors that reduce ethanol production.

Alginates↗

Viruses from extreme thermal environments.

Viruses of extreme thermophiles are of great interest because they serve as model systems for understanding the biochemistry and molecular biology required for life at high temperatures. In this work, we report the discovery, isolation, and preliminary characterization of viruses and virus-like particles from extreme thermal acidic environments (70-92 degrees C, pH 1.0-4.5) found in Yellowstone National Park. Six unique particle morphologies were found in Sulfolobus enrichment cultures. Three of the particle morphologies are similar to viruses previously isolated from Sulfolobus species from Iceland and/or Japan. Sequence analysis of their viral genomes suggests that they are related to the Icelandic and Japanese isolates. In addition, three virus particle morphologies that had not been previously observed from thermal environments were found. These viruses appear to be completely novel in nature.

Archaeal Viruses↗

Intragenic suppressors of an OmpF assembly mutant and assessment of the roles of various OmpF residues in assembly through informational suppressors.

We employed two separate genetic approaches to examine the roles of various OmpF residues in assembly. In one approach, intragenic suppressors of a temperature-sensitive OmpF assembly mutant carrying a W214E substitution were sought at 42 degrees C, or at 37 degrees C in a genetic background lacking the periplasmic folding factor SurA. In the majority of cases (58 out of 61 revertants), the suppressors mapped either at the original site (position 214) or two residues downstream from it. In the remaining three revertants that were obtained in a surA background, an alteration of N230Y was located 16 residues away from the original site. The N230Y suppressor also corrected OmpF315 assembly at 42 degrees C in a surA(+) background, indicating that the two different physiological environments imposed similar assembly constraints. The specificity of N230Y was tested against five different residues at position 214 of mature OmpF. Clear specificity was displayed, with maximum suppression observed for the original substitution at position 214 (E214) against which the N230Y suppressor was isolated, and no negative effect on OmpF assembly was noted when the wild-type W214 residue was present. The mechanism of suppression may involve compensation for a specific conformational defect. The second approach involved the application of informational suppressors (Su-tRNA) in combination with ompF amber mutations to generate variant OmpF proteins. In this approach we targeted the Y40, Q66, W214, and Y231 residues of mature OmpF and replaced them with S, Q, L, and Y through the action of Su-tRNAs. Thus, a total of 16 variant OmpF proteins were generated, of which three were identical to the parental protein, and two variants carrying W214Q and Y231Q substitutions were similar to assembly-defective proteins isolated previously (R. Misra, J. Bacteriol. 175:5049-5056, 1993). The results obtained from these analyses provided useful information regarding the compatibility of various alterations in OmpF assembly.

Amino Acid Sequence↗

Cloning and characterization of a novel Kruppel-associated box family transcriptional repressor that interacts with the retinoblastoma gene product, RB.

The retinoblastoma gene product, RB, seems to function as a key tumor suppressor by repressing the expression of genes activated by members of the E2F family of transcription factors. In order to accomplish this, RB has been proposed to interact with a transcriptional repressor. However, no genuine transcriptional repressors have been identified by virtue of interaction with RB. By using the yeast two-hybrid system, we have identified a novel member of a known family of transcriptional repressors that contain zinc fingers of the Kruppel type and a portable transcriptional repressor motif known as the Kruppel-associated box (KRAB). The mouse and human forms of the novel RB-associated KRAB protein (RBaK) are widely expressed. The amino acid motif that links the KRAB domain and zinc fingers appears to be required for interaction with RB in vitro. Human RBaK ectopically expressed in fibroblasts is an 80-kDa protein that is localized to the nucleus. The expression of either RB or RBaK in 10T1/2 fibroblasts represses the activation of an E2F-dependent promoter and decreases DNA synthesis to a similar degree. However, a mutant form of RBaK that cannot interact with RB in vitro is unable to prevent DNA synthesis. We present a model in which RB physically interacts with the novel transcriptional repressor RBaK to repress E2F-dependent genes and prevent DNA synthesis.

Amino Acid Sequence↗

Optimising the medical management of benign prostatic hyperplasia.

The ageing population is presenting an increasing demand on future healthcare services. In males, prostatic disease is one of the commonest disorders contributing to this. Alternatives to surgical intervention have to be considered as the preferred option for individuals and whether this be a therapeutic or a financial option to be taken. Two major medical alternatives are alpha-blockers and 5-alpha reductase inhibitors. The results of such treatment can be very beneficial in selected groups of patients. Side-effects with improved drugs electivity are reducing. Overall, while surgery still holds the gold standard, medical therapy has a significant role in the treatment of benign prostatic hypertrophy. Cost analysis may be a factor in deciding which treatment to have.

5-alpha Reductase Inhibitors↗

The fate of the defunctioned bladder following supravesical urinary diversion.

OBJECTIVE: To determine the nature, incidence and severity of bladder complications after supravesical urinary diversion without cystectomy and to identify preventative risk factors. PATIENTS AND METHODS: A retrospective study of the last 25 years identified 35 patients who had supravesical urinary diversion without concomitant cystectomy (33 ileal loop diversions and two cutaneous ureterostomies). Urinary diversion was performed for a variety of lower urinary tract pathologies. Patients with urinary tract neoplasia were excluded. There were 15 males (mean age 41 years, range 13-72) and 20 females (mean age 49 years, range 15-81) with a mean follow-up of 5.2 years (range 1-25). RESULTS: There were bladder complications in 10 patients (28%) including pyocystis (one mild and two severe), haemorrhage (two mild and one severe) and pain/spasm (four mild and three severe). Patients with interstitial cystitis, bladder outflow obstruction and/or a vesical fistula appeared to have a higher risk of complications. Four patients required cystectomy to treat severe symptoms while the remaining six achieved control of symptoms with no surgery. No patient developed carcinoma during the follow-up. CONCLUSION: We recommend that cystectomy is considered at the time of supravesical urinary diversion, particularly in patients with interstitial cystitis, bladder outflow obstruction or a chronically infected bladder and especially in those with a vesical fistula.

Adolescent↗

Idiopathic pulmonary fibrosis. Quantitative assessment of lung pathology. Comparison of a semiquantitative and a morphometric histopathologic scoring system.

The objective of this study was to determine the accuracy of a semiquantitative method of assessing the relative degree of cellularity and fibrosis compared with a morphometric analysis of specific histopathologic features in idiopathic pulmonary fibrosis (IPF). Morphometric analysis was performed on biopsy tissue from 20 patients. Morphometry showed that approximately 70% of parenchymal tissue was abnormal: 35% cellular consolidation and fibrosis, 20% honeycomb changes, 10% thick alveolar septa, and 5% small airways within abnormal parenchymal tissue. The prominent components of the abnormal parenchymal tissue were extracellular fibers, an abundance of interstitial cells, and epithelial cell hyperplasia. Correlation between four groupings of pathologic features, identified by a semiquantitative analysis, and each of the components of the parenchymal lesions showed significant correlations between (1) the fibrotic or reparative factor (alveolar wall metaplasia, fibrosis, honeycombing, and smooth muscle and vascular changes) and components of honeycomb lesions (extracellular fibers, interstitial cells, and epithelial injury and repair), and (2) the inflammatory and exudative factor and extracellular fibers in the lesions. These results support that the scoring system used by the pathology panel provides an accurate assessment of pathologic features useful in the assessment of the extent and severity of the histopathologic lesions of IPF.

Biopsy↗

Regional chemotherapy using continuous intravesical infusion doxorubicin for the treatment of muscle invasive transitional cell bladder carcinoma in a rat model.

Previously established animal models of invasive transitional cell bladder carcinoma and continuous infusion intravesical drug delivery were combined to evaluate the urothelial toxicity and antineoplastic efficacy of continuous intravesical infusion doxorubicin (DOX). Dose-response toxicity experiments studied histologic changes in the rat urinary bladder following urothelial exposure to three different urinary levels of DOX, as a function of the duration of drug infusion. Systemic and local drug absorption, as measured by DOX levels in serum, bladder, retroperitoneal lymph nodes, and liver, was measured at intervals during drug administration. In vitro chemosensitivity assays were used to determine tumor sensitivity to DOX. Treatment studies evaluated the impact of 14-day continuous infusion DOX beginning seven days following tumor implantation. No histologically discernable changes in the normal urothelium were noted in bladders of animals receiving continuous intravesicle DOX at mean urinary concentrations of 0.05 micrograms./ml. (n = 5), 0.56 micrograms./ml. (n = 10), and 5.69 micrograms./ml. (n = 10) for periods of up to 14 days. Serum drug concentrations demonstrated a non-significant upward trend following the start of therapy. Significant increases in tissue DOX levels were noted in the bladder and retroperitoneal lymph nodes on chemotherapy days 7 and 14. Mean tissue DOX concentrations in both the bladder and lymph nodes were greater than the IC50 observed in the in vitro sensitivity assay. DOX-treated tumor-bearing animals (n = 17) had a mean tumor volume (+/- standard deviation) of 0.65 gm. +/- 0.52 gm. compared to an average tumor volume of 1.20 gm. +/- 0.66 gm. in the control group (n = 18) (p = 0.0112). Continuous infusion intraluminal chemotherapy demonstrated a clear cytoreductive effect with minimal local toxicity in this model. Drug tissue levels were observed in regional lymphatic drainage fields as well as the bladder wall. Further study to evaluate this approach as a bladder-sparing alternative to muscle invasive disease is warranted.

Administration, Intravesical↗

A continuous intravesical drug delivery system for the rat.

We describe a self-contained system for the continuous infusion of drugs into the rat urinary bladder. A reversible model of hydronephrosis is used to prepare one renal unit for nephrostomy tube placement. An 0.8 mm. silastic nephrostomy tube is introduced into the hydronephrotic kidney via a 16 gauge angiocath. The nephrostomy tube is then connected to an Alzet mini osmotic pump which is implanted in a subcutaneous location. The ability of this system to deliver a continuous dose of a test agent into the bladder was evaluated. Pumps were filled with a 1% solution of methylene blue in phosphate buffered saline. Following pump implantation, urinary samples were collected on a daily basis and subsequently analyzed for their concentration of methylene blue. At the completion of the experiment, specimens of the kidney, ureter, and bladder were histologically examined. Results demonstrated an average of 102% recovery of the theoretically delivered dose over a 14-day period. Renal histology demonstrated chronic inflammatory changes at the site of nephrostomy tube placement. No upper or lower tract urothelial changes were identified. This model provides a system for the continuous delivery of drugs in the rat urinary tract and results in no histological alteration to the lower urinary tract.

Administration, Intravesical↗

Marginal adaptation and microleakage of thixotropic and injection-capsule composites, an in vitro study.

The marginal integrity of MOD adhesive restorations of a thixotropic test composite (ZKP-A-5) and of two injection-capsule composites (Concise -capsule composite and Compocap-S) was examined. Dy penetration tests measured microleakage and scanning electron microscope evaluated marginal adaptation. The test restorations showed no improved micromorphological marginal adaptation when compared to those of a standard paste-paste composite (Concise). Compocap-S demonstrated better prevention of microleakage than did the other test preparations. The marginal quality of these thixotropic and injection-capsule composite restorations was improved from 34% to 52% with utilization of a sealer application (ZKP-A-2), (Concise-Enamel Bond). The application of a sealer prior to insertion of thixotropic and injection-capsule composites is, therefore, definitely indicated when these materials are used. The resultant restorations obtained with these test materials plus sealer correspond qualitatively to those of standard composites Concise or Adaptic [6,7]. The newly developed, complete composite systems (Nimetic, GC's Epolite 100/Epobond) demonstrated in comparison to Concise and Adaptic [6,7] inferior results.

Adhesiveness↗