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Biomedical subjects

J A Roberts

Publications and source records attributed to J A Roberts.

At least 109 records · Page 6Linked to original sources

Effect of irrigating fluid on perioperative temperature regulation during transurethral prostatectomy.

Hypothermia in the immediate postoperative period is associated with postoperative instability, prolonged recovery and increased risk of myocardial ischemia in the subsequent 24 h. This study examined the effect of irrigating-fluid temperature during transurethral resection of the prostate on perioperative temperature regulation. A randomized prospective study was conducted on twenty-eight consecutive patients undergoing transurethral resections of the prostate. The control group received room-temperature irrigant. The study group received irrigant warmed through the Abbott level-one fluid warmer or in the Ohio Servocare incubator. Fluid temperatures were 17 degrees C for unwarmed fluid, 37 degrees C for level-one fluid, and 35 degrees C for incubator fluid. The incidence of hypothermia (< or = 36 degrees C) in the immediate postoperative period was 95% in the cold-irrigant group and 38% in the warm-irrigant group (p = 0.001). The decrease from pre- to postoperative temperature was greater with cold (0.95 +/- 0.47 degrees C) than with warm (0.42 +/- 0.64 degrees C) irrigant (p = 0.01). The type of anesthesia (spinal versus general) and method of fluid warming (incubator versus level-one) did not have a significant effect on the perioperative temperature drop. Regression analysis demonstrated that the time of resection, amount of prostate resected, volume of irrigant fluid, and volume of intravenous fluid administered were not independent predictors of intraoperative temperature change.

Aged↗

Tropism in bacterial infections: urinary tract infections.

PURPOSE: Tropism describes the phenomenon by which commensal and pathogenic bacteria are restricted to certain hosts, tissue and cell types. This review was done to shed light on the initiating factors in bacterial disease, more particularly those responsible for urinary tract infections. MATERIALS AND METHODS: The literature was reviewed on the tropism of several common bacterial infections with an extensive evaluation of tropism at the molecular level in urinary tract infections. RESULTS: Interaction of bacteria with certain tissues, cells and molecules is described. Initially, bacterial adhesion occurs via bacterial fimbriae in the case of gram-negative bacteria, while gram-positive bacteria adhere more frequently via extracellular polysaccharides. Urinary tract infections occur most frequently because of adherence via P-fimbriae of Escherichia coli. P-fimbriae are important in cystitis as well, while type 1 fimbriae and nonfimbrial adhesins may also be responsible for its initiation. CONCLUSIONS: The usual initiating mechanism in bacterial infections involves bacterial adhesion to specific molecules on cell surfaces, followed by invasive disease. The tip proteins of P-fimbriae of Escherichia coli lead to the initiation of urinary tract infection. Understanding the molecular events responsible may lead to development of a vaccine to prevent urinary tract infection.

Bacterial Adhesion↗

Iodine-123-5-iodo-6-nitroquipazine: SPECT radiotracer to image the serotonin transporter.

UNLABELLED: Because serotonergic function has been implicated in the pathophysiology of a number of diseases of the nervous system, efforts to image this system in vivo have received considerable recent attention. Promising preliminary results with the tracer 5-iodo-6-nitroquipazine (INQUIP) have prompted us to perform further studies designed to validate the use of the tracer as an in vivo ligand for the serotonin transporter. METHODS: We studied six adult macaca mulatta in eight experiments which involved SPECT imaging at 17 to 24 hr post-tracer injection, including three experiments with coinjection of the 123I-and 125I-radiolabeled tracer for direct comparison of autoradiography and SPECT, and three experiments in which animals were lesioned with the serotonergic neurotoxin (+/-)3,4-methyl-enedioxymethamphetamine (MDMA). In addition, we evaluated the metabolism of the tracer in the brain and periphery. RESULTS: SPECT images obtained at 17 and 24 hr reflected the known pattern of distribution of serotonin transporters and also showed close correspondence to the autoradiograms. Ratios of binding in the brain-stem to binding in the cerebellum were close to 3 at 17 hr. autoradiograms from an MDMA-treated animal showed up to 95% reductions of binding, while the SPECT data showed smaller reductions. Virtually all of the tracer in the brain stem was in the form of unmetabolized parent compound, but plasma showed rapid peripheral metabolism of the tracer. CONCLUSION: These results demonstrate that INQUIP SPECT images are sensitive measures of in vivo binding to the serotonin transporter, and support the further development of the tracer as a method for the in vivo study of serotonergic neurons in humans.

Animals↗

Travel prophylaxis.

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Cost-Benefit Analysis↗

Neovaginal cytology after total pelvic exenteration for gynecological malignancies.

Vaginal reconstruction has become an established method to restore sexual function in women who have undergone ultraradical surgery and/or irradiation for the treatment of gynecologic malignancies. Cytologic evaluation of the neovagina serves a major role in the detection of recurrent disease. The purpose of this retrospective 6-yr study (January 1987-December 1993) was to evaluate the cytologic features of vaginal smear specimens from neovaginas constructed utilizing split-thickness skin grafts. Thirty-four vaginal smears were obtained at regular intervals from nine women (mean age: 51 yr) who underwent total pelvic exenteration with vaginal reconstruction for recurrent malignancies of the vagina and the cervix. Anucleated, keratinizing squames were a constant finding in each smear. Over a 4-mo-6-yr postoperative period, superficial and intermediate squamous cells were present in the majority of the smears and the maturation index showed a shift to the right. In two cases, a squamous cell carcinoma of the cervix recurred within the neovagina. Knowledge of the cytologic features associated with neovaginas is important in order to distinguish normal changes from neoplastic lesions.

Adenocarcinoma↗

Characterisation of an mRNA encoding a metallothionein-like protein that accumulates during ethylene-promoted abscission of Sambucus nigra L. leaflets.

A cDNA encoding a metallothionein-like protein has been isolated from a cDNA library from the abscission zones of ethylene-treated Sambucus nigra leaflets. The precise function of this group of proteins in plants has yet to be confirmed but in animals there is convincing evidence that they bind heavy metals. Several of these proteins have recently been characterised from plants and it has been demonstrated that heavy metals have no stimulatory effect on their expression. In this paper we describe the isolation and characterisation of a metallothionein-like mRNA identified as a consequence of differentially screening a cDNA library for messages up-regulated during abscission. The accumulation of the mRNA occurred in the abscission zone tissue within 18 h of exposure to ethylene while, in contrast, no expression was detectable in adjacent non-abscission-zone tissue. The transcript size of the message was approximately 0.6 kb. Northern analysis revealed that the cDNA insert (JET12) did not hybridise to mRNA from either green or senescing leaflets but a signal was detectable with mRNA extracted from senescent tissue. The size of this hybridising transcript was approximately 0.5 kb. The predicted metallothionein-like protein encoded by JET12 was cysteine-rich (18.4%) and had a molecular weight of approximately 7.5 kDa. Southern analysis of S. nigra genomic DNA showed that the mRNA was encoded by a small gene family. The protein exhibited greatest homology to other metallothioneins belonging to the Type 2 family including those from Mimulus (62%) and Arabidopsis (57%). This homology was greatest around the cysteine-rich amino and carboxy termini.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acid Sequence↗

Cytokine and lymphocyte activation during experimental acute pyelonephritis.

We studied the cellular and humoral events which follow experimental acute pyelonephritis from P-fimbriated Escherichia coli to gain insight into the relationships among cells and specifically cytokines to determine how early events in untreated infection lead to renal damage. Cynomolgus (Macaca fascicularis) monkeys were studied after they were subjected to unilateral ureteral bacterial inoculation. We evaluated the blood for leukocytosis and studied lymphocyte subsets using flow cytometry and monoclonal antibodies to the subsets and serum, complement, cytokines and antibody titers. Interleukin-1, 2 and 6 and tumor necrosis factor (TNF) were assayed by enzyme-linked immunoadsorbent assay (ELISA), using monoclonal and polyclonal antibodies. Leukocytosis was marked and there were significant elevations in serum cytokines, interleukin-1 alpha, 2 and 6 with only small changes in the level of TNF. Interleukin-2 levels were sustained and may have upregulated the homing receptor for virgin lymphocytes. The studies illustrated the unique relationship between cytokines and lymphocytes and the response to bacterial infection, showing that the inflammatory response is regulated not only by cytokine activity but also by lymphocyte activation.

Acute Disease↗

The possible role of granulocyte elastase in renal damage from acute pyelonephritis.

During acute inflammatory processes, extracellular release of granulocyte elastase can contribute to subsequent tissue damage. To test our hypothesis that extracellular elastase release during acute pyelonephritis may contribute to subsequent renal parenchymal damage, we compared the intracellular and extracellular activities of the lysozyme elastase of human polymorphonuclear cells (PMN) when incubated in vitro with bacterial strains causing renal infection that led to either renal damage or no damage. Urine bacterial cultures were obtained from patients with acute pyelonephritis (flank pain, costovertebral angle tenderness, fever > 38 degrees C, bacteriuria, pyuria, and leukocytosis). Renal damage was demonstrated by cortical scarring on followup intravenous pyelography and/or diminished function on 131iodine hippuran renal scan. Mean extracellular elastase activity (mu units/PMN) was 0.15 for unstimulated PMN, 0.07 for PMN stimulated by bacteria not associated with renal damage, and 1.20 for the PMN stimulated by strains associated with renal damage. Mean intracellular elastase activity (mu units/PMN) was 3.73 for unstimulated PMN, 3.48 for PMN stimulated by bacteria not associated with renal damage, and 3.31 for the PMN stimulated by strains associated with renal damage. Extracellular granulocyte elastase activity was thus significantly higher (P = 0.0001) in PMN stimulated by bacterial strains associated with renal damage. Extracellular release of elastase may contribute to the pathogenesis of renal damage in pyelonephritis.

Acute Disease↗

Vaccination with a formalin-killed P-fimbriated E. coli whole-cell vaccine prevents renal scarring from pyelonephritis in the non-human primate.

A formalin-killed P-fimbriated Escherichia coli serotype O4 vaccine was evaluated for protective efficacy in monkeys in an experimental pyelonephritis model following urethral bacterial inoculation. The vaccination did not protect against initial colonization and there were no significant differences in the time of bacteriuria after experimental infection in the two groups of animals. The whole-cell vaccine offers a limited protection against renal dysfunction and scarring (p = 0.002) and less renal involvement (p = 0.04), results that are quite similar to those given by a synthetic O-antigen-specific saccharide-protein conjugate vaccine previously tested.

Analysis of Variance↗

cAMP and PMA enhance the effects of IGF-I in the proliferation of endometrial adenocarcinoma cell line HEC-1-A by acting at the G1 phase of the cell cycle.

The present study was undertaken to determine whether endometrial cancer cell line HEC-1-A differ from nontransformed cells, in that the cAMP and protein kinase C pathways may enhance IGF-I effects in mitogenesis by acting at the G1 phase of the cell cycle instead of G0. Immunofluorescence staining of HEC-1-A cells using the proliferating cell nuclear antigen (PCNA) monoclonal antibody and flow cytometric analysis determined that HEC-1-A cells do not enter the G0 phase of the cell cycle when incubated in a serum-free medium. Approximately 51% of the cells were in G1, 12% were in S and 37% in G2 phase of the cell cycle prior to treatment. Forskolin and phorbol-12-myristate 13-acetate (PMA) were used to stimulate cAMP production and protein kinase C activity, respectively. IGF-I, forskolin and PMA each increased (P < 0.01) [3H]-thymidine incorporation in a dose and time dependent manner. The interaction of forskolin and PMA with IGF-I was then determined. Cells preincubated with forskolin or PMA followed by incubation with IFG-I incorporated significantly more (P < 0.01) [3H]-thymidine into DNA than controls or any treatment alone. It is concluded that forskolin and, to a lesser extent, PMA exert their effect at the G1 phase of the cycle to enhance IGF-I effects in cell proliferation.

8-Bromo Cyclic Adenosine Monophosphate↗

Treatment of chronic type B and C hepatitis with interferon alfa: an economic appraisal.

The aim of this study is to assess the long-term economic impact of treatment of chronic hepatitis B and C with interferon alfa. Estimates were made of the progression of the disease over a 30-year period using a transitional probability model. Cohorts of 1,000 hypothetical patients with either chronic hepatitis B or C treated with interferon alfa were compared with an untreated cohort. The costs were estimated for therapy, monitoring, and treatment of the disease, including transplantation. The cost-effectiveness of therapy was expressed in terms of cost per life saved, cost per year of life saved, and cost per quality-adjusted year of life saved. The analysis was extended to include the indirect costs to patients. The analysis included two rates of progression, two mortality rates, and discounted and undiscounted costs. Mortality in the treated group was lower, saving 18 to 31 lives in the hepatitis B virus (HBV) cohort and 13 to 22 lives in the hepatitis C virus (HCV) cohort. Fewer patients progressed to cirrhosis or decompensated cirrhosis. Discounted costs per year of life saved ranged from 2,142 pounds to 17,128 pounds. A cost-benefit analysis indicated excess benefits over costs when values for life were included in the analysis. The potential usefulness of interferon alfa on the clinical and economic outcome of treatment is indicated from the model. These findings together with the benefits that are likely to accrue from the reduction in infectious individuals suggest that this therapy has a role to play in public health policy to contain the impact of hepatitis.

Adult↗

Treatment of refractory ovarian carcinoma with paclitaxel and cisplatin after treatment failure with single-agent paclitaxel.

The clinical response to paclitaxel and cisplatin was evaluated in fifteen patients with refractory epithelial ovarian cancer who failed to respond to treatment with single agent paclitaxel. Patients received combination chemotherapy every 3 weeks with both 135 mg/m2 (9) or 175 mg/m2 (6) of paclitaxel and 50 mg/m2 (2), 75 mg/m2 (4) or 100 mg/m2 (9) of cisplatin. There was 1 complete clinical response, with 2 partial clinical responses for an overall response rate of 20%. The progression free interval was 6+ months for the complete responder and 9.5+ months for the partial responders. Overall five (33%) patients experienced an improvement in clinical response over that seen with paclitaxel alone, and 5 patients have died. Improvement in clinical response with combination chemotherapy compared to paclitaxel alone was positively associated with the cisplatin dose; while disease progression and death were inversely associated with the paclitaxel dose. Addition of cisplatin to paclitaxel may be useful in the treatment of patients who fail to respond to paclitaxel alone.

Adult↗

The Gal(alpha 1-4)Gal-specific tip adhesin of Escherichia coli P-fimbriae is needed for pyelonephritis to occur in the normal urinary tract.

Nonobstructive acute pyelonephritis in humans is most often caused by P-fimbriated Escherichia coli. P-fimbriae are heteropolymeric fibers carrying a Gal(alpha 1-4)Gal-specific PapG adhesin at its distal end. The pyelonephritic strain DS17 expresses P-fimbriae from a single gene cluster. A mutant strain, DS17-8, which expresses P-fimbriae tacking the PapG adhesin, was constructed by allelic replacement introducing a 1-bp deletion early in the papG gene. In cynomolgus monkeys, DS17 and DS17-8 were equally able to cause bladder infection, whereas only the wild-type strain DS17 could cause pyelonephritis as monitored by bacteriological, functional, and histopathological criteria. Since DS17, but not DS17-8, adheres to renal tissue, these data underscore the critical role of microbial adherence to host tissues in infectious disease and strongly suggest that the PapG tip adhesin of P-fimbriae is essential in the pathogenesis of human kidney infection.

Adhesins, Escherichia coli↗