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Biomedical subjects

J W Evans

Publications and source records attributed to J W Evans.

At least 19 recordsLinked to original sources

Haemodynamic evidence for cardiac stress during transurethral prostatectomy.

OBJECTIVE: To compare haemodynamic performance during transurethral prostatectomy and non-endoscopic control procedures similar in duration and surgical trauma. DESIGN: Controlled comparative study. SETTING: London teaching hospital. PATIENTS: 33 men aged 50-85 years in American Society of Anesthesiologists risk groups I and II undergoing transurethral prostatectomy (20), herniorrhaphy (eight), or testicular exploration (five). MAIN OUTCOME MEASURES: Percentage change from baseline in mean arterial pressure, heart rate, Doppler indices of stroke volume and cardiac output, and index of systemic vascular resistance, and change from baseline in core temperature. RESULTS: In the control group mean arterial pressure fell to 11% (95% confidence interval -17% to -5%) below baseline at two minutes into surgery and remained below baseline; there were no other overall changes in haemodynamic variables and the core temperature was stable. During transurethral prostatectomy mean arterial pressure increased by 16% (5% to 27%) at the two minute recording and remained raised throughout. Bradycardia reached -7% (-14% to 1%) by the end of the procedure. Doppler indices of stroke volume fell progressively to 15% (-24% to -6%) below baseline at the end of the procedure, and the index of cardiac output fell to 21% (-32% to -10%) below baseline by the end of the procedure. The index of systemic vascular resistance was increased by 28% (17% to 38%) at two minutes, and by 46.8% (28% to 66%) at the end of the procedure. Core temperature fell by a mean of 0.8 (-1.0 to -0.6) degrees C. Significant differences existed between the two groups in summary measures of mean arterial pressure (p less than 0.05), Doppler indices of stroke volume (p less than 0.005) and cardiac output (p less than 0.005), index of systemic vascular resistance (p less than 0.0005), and core temperature (p less than 0.0001). CONCLUSIONS: Important haemodynamic disturbances were identified during routine apparently uneventful transurethral prostatectomy but not during control procedures. These responses may be related to the rapid central cooling observed during transurethral prostatectomy and require further study.

Aged

The frequency of translocations after treatment for Hodgkin's disease.

We studied the frequency of translocations in peripheral blood lymphocytes of patients with Hodgkin's disease to determine the extent of chromosome changes induced by radiation or radiation and chemotherapy. Comparisons were made to patients with second cancers to determine if this population is more susceptible to the effects of treatment. Group one included six patients with newly diagnosed Hodgkin's disease who were treated with radiation only. Group two included Hodgkin's disease patients who were treated 12-24 years previously and have been continuously free of disease. Five of these patients were treated with radiation only and five patients received radiation and mechlorethaminehydrochloride, oncovin, procarbazine, prednisone (MOPP) chemotherapy for six cycles. Group three included three patients who developed a second cancer after successful treatment for Hodgkin's disease. Two of these patients had a sarcoma within the radiation field and one had breast cancer. Metaphase spreads were obtained from cultured lymphocytes and hybridized with a chromosome 4 specific probe. After fluorescein staining, approximately 1000 metaphases were scored per patient. In group one only one patient in six demonstrated translocations in chromosome 4 before treatment for a mean frequency of .0009. After treatment the frequency of translocations increased to a mean of .016 (p = .036) (range .006-.034). Group two patients treated with radiation only had a mean translocation frequency of .012 (range .004-.022) in comparison to the radiation/mechlorethaminehydrochloride, oncovin, procarbazine, prednisone chemotherapy treated patients who demonstrated a mean frequency of .016 (p = .425) (range .0009-.023). The third group of second cancer patients showed inconsistent translocation frequencies of .002, .020, and .035. Of these patients, the one who demonstrated the greatest frequency of translocations (.035) was treated with mechlorethaminehydrochloride, oncovin, procarbazine, prednisone/adriamycin, bleomycin, vinblastine, decadron) and radiation. Our data demonstrates a statistically significant increase in translocations detected after radiation. When compared to combined modality therapy a greater mean frequency of translocations is observed over radiation alone; however, this was not statistically significant. In the three patients who developed second cancers in our series we saw no consistent increase in translocation frequency compared to Hodgkin's disease patients who did not develop a second cancer.

Antineoplastic Combined Chemotherapy Protocols

The hypersensitivity of the Chinese hamster ovary variant BL-10 to bleomycin killing is due to a lack of glutathione S-transferase-alpha activity.

As a means to understand the fundamental mechanisms of bleomycin cell killing, we previously isolated 19 bleomycin-sensitive mutants which represent at least six genetically distinct complementation groups (T.D. Stamato, B. Peters, P. Patil, N. Denko, R. Weinstein, and A. Giaccia. Cancer Res., 47: 1588-1592, 1987). One class of mutants represented by the cell line BL-10 displays only hypersensitivity to killing by bleomycin in both acute (16 h) and chronic treatments but no sensitivity to killing by other DNA-damaging agents. Complementation studies between this mutant and human fibroblasts suggested that the human gene which corrects the defect of BL-10 rested on human chromosome 6. It has been reported that the gene for human glutathione S-transferase (GST) alpha also resides on chromosome 6. Measurements of selenium-independent peroxidase (alpha-GST + glutathione peroxidase) activity in wild-type Chinese hamster ovary (CHO) cells, using cumene hydrogen peroxide as a substrate, gave a value of 112 nmol of glutathione oxidized/min/mg protein compared with 88.1 nmol of glutathione oxidized/min/mg protein for BL-10. Measurement of the selenium-dependent peroxidase activity, using H2O2 as a substrate, resulted in 65.9 nmol of reduced glutathione oxidized/min/mg protein in CHO and 81.5 nmol of reduced glutathione oxidized/min/mg protein for BL-10. In other words, BL-10 cells did not exhibit a difference in their ability to metabolize both substrates in contrast to CHO cells. This indicates that BL-10 possesses little alpha-GST activity. Transfection of BL-10 cells with a mammalian expression vector containing the alpha-GST gene increases the survival of BL-10 to bleomycin and does not increase the bleomycin resistance of two other bleomycin mutants which lie in different genetic complementation groups. These data strongly implicate a role for alpha-GST in the resistance of cells to bleomycin.

Animals

Loss of the intrinsic heat resistance of human cells and changes in Mr 70,000 heat shock protein expression in human x hamster hybrids.

Since mammalian cells vary widely in their intrinsic thermoresistance, we have investigated the genetic basis underlying this phenomenon in human and rodent cell lines. Typically, human cells are considerably more resistant to killing by heat than rodent cell lines. To determine whether the heat-resistant phenotype is dominant or recessive and to locate the chromosome(s) bearing determinants for heat resistance, we have prepared hybrids of heat-resistant human HT1080 cells and heat-sensitive Chinese hamster ovary (CHO) cells to test their response to heat. For both mass hybrid cultures and individual clones, the heat response of the hybrids was similar to that of the CHO parent. Analysis by in situ hybridization revealed the presence of five to 20 human chromosomes per cell in the mass hybrids and four to eight intact chromosomes plus some fragments in individual clones isolated from the hybrid cell population. A similar result was obtained using a different human cell line, AG1522. These data suggest that heat resistance is a recessive trait. Consistent with this conclusion are the results from a study of a fusion of HT1080 to a CHO mutant, BL-10, which was found to be hypersensitive to heat-induced killing. These hybrids had a normal CHO heat response and not the more heat-resistant phenotype of HT1080 cells. Two hybrid clones, H2 and H4, from the HT1080/BL-10 fusion were studied in more detail. Both clones possess similar amounts of Mr 70,000 heat shock protein (HSP70), despite the fact that H4 contains three human chromosomes (Nos. 6, 14, and 21) which carry HSP70 genes while H2 contains only one (chromosome 6). Both hybrid cell lines have the same response to heat. Although we found a wide range of sensitivities to heat, all cell lines contained a similar amount of constitutive HSP70, suggesting that HSP70 levels per se are not the critical determinant of intrinsic heat resistance.

Animals

The use of fluorescence in situ hybridisation combined with premature chromosome condensation for the identification of chromosome damage.

The technique of fusing mitotic cells to interphase cells, thereby producing condensation of the chromosomes of the interphase cell (so-called 'premature chromosome condensation' or PCC), has allowed detection of the initial number of chromosome breaks and their repair following ionising radiation. However, the difficulty and tedium of scoring all the chromosome fragments, as well as the inability to readily detect exchange aberrations, has limited the use of PCC. We describe here the use of the recently developed technique of fluorescence in situ hybridisation with whole chromosome libraries to stain individual human chromosomes (also called 'chromosome painting') with the PCC's and show that this overcomes most of the limitations with the analysis of PCC's. First, by focusing on a single chromosome, scoring of breaks in the target chromosome is easy and rapid and greatly expands the radiation dose range over which the PCC technique can be used. Second, it allows the easy recognition of exchange type aberrations. A number of new applications of this technology, such as predicting the radiosensitivity of human tumours in situ, are feasible.

Cell Line

Haemodynamic evidence for per-operative cardiac stress during transurethral prostatectomy. Preliminary communication.

Haemodynamic changes were measured during routine transurethral prostatectomy (TURP). The heart rate and stroke volume fell progressively over the first 30 min of surgery, resulting in a steady reduction in cardiac output. There was a significant increase in left ventricular afterload from commencement of the procedure. These findings demonstrate that haemodynamic responses, which are not detectable using conventional methods of monitoring, occur during TURP. Increased left ventricular afterload indicates increased myocardial work and oxygen demand which could result in myocardial ischaemia. This may contribute to the increased cardiovascular morbidity and mortality which have been reported to occur after TURP. The possible underlying mechanisms are discussed.

Aged

Viability and ultrastructure of equine embryos following culture in a static or dynamic system.

The viability and ultrastructure of equine embryos were assessed following culture in a static or perifusion system. The percentage change in diameter was greater (P less than 0.025) for embryos in the static treatment (71%) than in the perifusion treatment (33%). Fluorescein diacetate (FD) scores, the percentage of fluorescing cells (FC) and fluorescent intensity (FI), also were greater (P less than 0.05 and P less than 0.01) following static culture than for embryos cultured in the perifusion system. Four of 9 control embryos resulted in pregnancies but no embryos cultured in either system prior to transfer resulted in pregnancies. Three of 9 embryos in the static treatment group and 1 of 9 embryos in the perifusion group resulted in non-ecogenic vesicles. Ultrastructural evaluation agreed with FD scores and morphological assessment. The continued development of static cultured embryos without the presence of an inner cell mass (ICM) was supported by ultrasound data.

Animals

Post prostatectomy bladder neck contractures.

An 8% and 7% incidence of bladder neck contractures (BNC) requiring relief by transurethral incisions (TUI), (124) was found after review of 1471 TURP's and 71 retropubic prostatectomies. Prevention of BNC was attempted by leaving a one centimeter strip at the time of TURP (62), incising the bladder neck alone (42), or incising the bladder neck and interureteric ridge (65). Bladder neck obstruction occurred in 4.8% of the strips, 14% of the incised bladder necks only, and 3% of the incised bladder neck and contiguous interureteric ridges. A significant cost savings is possible.

Contracture

Use of fluorescent in situ hybridization to detect chromosomal rearrangements in somatic cell hybrids.

In situ hybridization of hamster/human hybrids with biotinylated human genomic DNA has revealed that human chromosomal DNA can integrate into the hamster genome and is not always cytologically detectable. This finding helps to explain why discordancy can arise in gene mapping by failing to recognize small pieces of foreign DNA in the rodent genome. Fluorescent in situ hybridization allows one to locate these fragments in rodent chromosomes visually and possibly to identify their chromosome of origin.

Animals

Bladder calculus formation as a complication of the Stamey procedure.

Three cases of bladder stone due to a migrated Stamey suture and cuff are reported. In each case peroperative cystoscopy confirmed that the sutures were extravesical. The Stamey cuff subsequently formed a nidus for intravesical stone formation. The mechanism of migration of the cuff, the radiological findings and the operative technique are discussed.

Aged

Growth performance of yearling horses grazing bermudagrass pastures at different grazing pressures.

Body weight gains and height at the withers were measured in yearling geldings grazing bermudagrass (Cynodon dactylon [L.] Pers.) pastures with neither energy nor protein feed supplementation at stocking rates of 6.7, 8.0, 9.5 and 12.4 yearlings per hectare. Weekly forage samples were taken to estimate the quantity and quality of available forage. These samples were clipped and separated into three equal lengths to characterize upper, middle and lower thirds of the canopy and to determine relationships between available forage and yearling growth rate. Average daily gain was influenced by stocking rate, but gain in height was not affected by stocking rate. Average daily gain ranged from -.31 to .37 kg/d and was negatively related to stocking rate. A quadratic relationship between available forage and ADG was detected. However, a linear relationship between ADG and available forage in top layers of the canopy indicated that animal performance might have been limited by availability of top layer forage in pastures subjected to light grazing pressure.

Analysis of Variance

Follicular growth and estradiol influence on luteal function in mares.

Follicular growth, circulating estradiol concentrations and endometrial prostaglandin F2 alpha (PGF2 alpha) production were measured to determine whether there is an interrelationship among these factors associated with luteolysis. Follicular growth was monitored by rectal palpation every other day during diestrus in 16 mares. Plasma estradiol was determined for daily samples during all estrous cycles. Endometrial tissue was removed for PGF2 alpha analysis by radioimmunoassay on d 10, 12, 14 or 16 during several normal cycles and after d 30 during spontaneously prolonged cycles. Circulating estradiol concentrations were highly correlated with follicular diameter. Follicular growth was initiated before d 14 in normal cycles, thus estradiol was significantly elevated during the portion of diestrus prior to luteolysis. This was not the case during spontaneously prolonged cycles in which a) there was no correlation between follicular size and circulating estradiol, b) follicular growth was initiated an average of 19 d postovulation, and c) estradiol concentrations did not increase. Diestrous estradiol concentrations, during normal cycles, were significantly elevated immediately (72 to 24 h) prior to the time at which peak endometrial PGF2 alpha production occurred (d 12 and 14). During spontaneously prolonged cycles, estradiol concentrations did not rise at the time of expected luteolysis, and endometrial PGF2 alpha production was minimal in d 30 biopsies. Results suggest that diestrus follicular growth and its consequent estradiol production may play a role in initiating luteolysis through endometrial PGF2 alpha production and that delay or failure of this process may result in spontaneously prolonged corpora luteal function.

Animals