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Biomedical subjects

R L Harris

Publications and source records attributed to R L Harris.

At least 19 recordsLinked to original sources
PubMed2005

Derivative chromosome 9 deletions are a significant feature of childhood Philadelphia chromosome positive acute lymphoblastic leukaemia.

Deletions from the derivative chromosome 9, der(9), of the translocation, t(9;22)(q34;q11), at the site of the ABL/BCR fusion gene, have been demonstrated by fluorescence in situ hybridisation (FISH), in both Philadelphia chromosome (Ph)-positive chronic myeloid leukaemia (CML) and acute lymphoblastic leukaemia (ALL). In CML they occur in 10-15% of cases and appear to indicate a worse prognosis, whereas in ALL, the situation is unclear. This study presents the findings of dual fusion FISH used to detect such deletions in a series of 27 BCR/ ABL-positive childhood ALL patients. Metaphase FISH was essential for the accurate interpretation of interphase FISH signal patterns. Three cases (11%) had a single fusion signal, resulting from deletions of the der(9). Three other patients with variant translocations and one with an insertion, also had a single fusion, but with no evidence of deletions. Gain of a fusion in approximately one-third of patients indicated a second Ph, which appears to be a diagnostic marker of Ph-positive ALL. This study shows that the incidence of deletions from the der(9) in childhood ALL is at least as high as that reported for CML.

Child↗
PubMed2004

Effectiveness of intermediate care in nursing-led in-patient units.

BACKGROUND: The Nursing led inpatient Unit (NLU) is one of a range of services that have been considered in order to manage more successfully the transition between hospital and home for patients with extended recovery times. OBJECTIVES: To determine whether nursing-led inpatient units are effective in preparing patients for discharge from hospital compared to usual inpatient care. SEARCH STRATEGY: We searched The Cochrane Library, the Specialized Register of the Cochrane Effective Practice and Organisation of Care (EPOC) group, MEDLINE, CINAHL, EMBASE, BNI and HMIC databases. Citation searches were undertaken on the science and social science citation indices. Authors were contacted to identify additional data. SELECTION CRITERIA: Controlled trials and interrupted time series designs that compared the NLU to usual inpatient care managed by doctors. Patients over 18 years of age following an acute hospital admission for a physical health condition. DATA COLLECTION AND ANALYSIS: Two reviewers independently extracted data and assessed study quality. MAIN RESULTS: Ten random or quasi-random controlled trials reported on a total of 1896 patients. There was no statistically significant effect on inpatient mortality ( OR 1.10, 95% CI 0.56 to 2.16) or mortality to longest follow up (OR 0.92, 95% CI 0.65 to 1.29) but higher qaulity studies showed a larger non-significant increase in inpatient mortality (OR 1.52, 95% CI 0.86 to 2.68). Discharge to institutional care was reduced for the NLU (OR 0.44 95% CI 0.22 to 0.89) and functional status at discharge increased (SMD 0.37, 95% CI 0.20 to 0.54) but there was a near significant increase in inpatient stay (WMD 5.13 days 95% CI -0.5 days to 10.76 days). Early readmissions were reduced (OR 0.52 95% CI 0.34 to 0.80). One study compared a NLU for the chronically critically ill with ICU care. Mortality (OR 0.62 95% CI 0.35 to 1.10) and length of inpatient stay differ did not differ (WMD 2 days, 95% CI 10.96 to -6.96 days). Early readmissions were reduced (OR 0.33 95% CI 0.12 to 0.94). Costs of care on the NLU were higher for UK studies but lower for US based studies. REVIEWERS' CONCLUSIONS: There is some evidence that patients discharged from a NLU are better prepared for discharge but it is unclear if this is simply a product of an increased length of inpatient stay. No statistically significant adverse effects were noted but the possibility of increased early mortality cannot be discounted. More research is needed.

Health Care Costs↗
PubMed2001

Evidence that F-plasmid proteins TraV, TraK and TraB assemble into an envelope-spanning structure in Escherichia coli.

We have examined the role of the F-plasmid TraV outer membrane lipoprotein in the assembly of F-pili. Yeast two-hybrid analysis with a traV bait repeatedly identified traK, which is predicted to encode a periplasmic protein, among positive prey plasmids. A traK bait in turn identified traV and traB, which is predicted to encode an inner membrane protein. A traB bait exclusively identified traK preys. Several additional observations support the hypothesis that TraV, TraK and TraB form a complex in Escherichia coli that spans the cell envelope from the outer membrane (TraV) through the periplasm (TraK) to the inner membrane (TraB). First, two-hybrid analyses indicated that TraV and TraB bind to different TraK segments, as required if TraK bridges a ternary complex. Secondly, all three proteins fractionated with the E. coli outer membrane in tra+ cells. In contrast, TraB fractionated with the inner membrane in traV or traK mutant cells, and TraK appeared in the osmotic shock fluid from the traV mutant. These results are consistent with a TraV-TraK-TraB complex anchored to the outer membrane via the TraV lipoprotein. Further, in traK mutant cells, TraV failed to accumulate to a detectable level, and the TraB level was significantly reduced, suggesting that TraV and TraB must interact with TraK for either protein to accumulate to its normal level. Both TraK and TraV accumulated in traB2[Am] cells; however, the TraB2 amber fragment could be detected by Western blot, and sequence analysis indicated that the fragment retained the TraK-binding domain suggested by yeast two-hybrid analysis. We propose that TraV is the outer membrane anchor for a trans-envelope, Tra protein structure required for the assembly of F-pili and possibly for other events of conjugal DNA transfer.

Bacterial Proteins↗
PubMed1999

A comparison of two antimicrobial-impregnated central venous catheters. Catheter Study Group.

BACKGROUND: The use of central venous catheters impregnated with either minocycline and rifampin or chlorhexidine and silver sulfadiazine reduces the rates of catheter colonization and catheter-related bloodstream infection as compared with the use of unimpregnated catheters. We compared the rates of catheter colonization and catheter-related bloodstream infection associated with these two kinds of antiinfective catheters. METHODS: We conducted a prospective, randomized clinical trial in 12 university-affiliated hospitals. High-risk adult patients in whom central venous catheters were expected to remain in place for three or more days were randomly assigned to undergo insertion of polyurethane, triple-lumen catheters impregnated with either minocycline and rifampin (on both the luminal and external surfaces) or chlorhexidine and silver sulfadiazine (on only the external surface). After their removal, the tips and subcutaneous segments of the catheters were cultured by both the roll-plate and the sonication methods. Peripheral-blood cultures were obtained if clinically indicated. RESULTS: Of 865 catheters inserted, 738 (85 percent) produced culture results that could be evaluated. The clinical characteristics of the patients and the risk factors for infection were similar in the two groups. Catheters impregnated with minocycline and rifampin were 1/3 as likely to be colonized as catheters impregnated with chlorhexidine and silver sulfadiazine (28 of 356 catheters [7.9 percent] vs. 87 of 382 [22.8 percent], P<0.001), and catheter-related bloodstream infection was 1/12 as likely in catheters impregnated with minocycline and rifampin (1 of 356 [0.3 percent], vs. 13 of 382 [3.4 percent] for those impregnated with chlorhexidine and silver sulfadiazine; P<0.002). CONCLUSIONS: The use of central venous catheters impregnated with minocycline and rifampin is associated with a lower rate of infection than the use of catheters impregnated with chlorhexidine and silver sulfadiazine.

Analysis of Variance↗
PubMed1999

Interaction between the F plasmid TraA (F-pilin) and TraQ proteins.

Elaboration of conjugative (F) pili by F+ strains of Escherichia coli requires the activities of over a dozen F-encoded DNA transfer (Tra) proteins. The organization and functions of these proteins are largely unknown. Using the yeast two-hybrid assay, we have begun to analyse binary interactions among the Tra proteins required for F-pilus formation. We focus here on interactions involving F-pilin, the only known F-pilus subunit. Using a library of F tra DNA fragments that contained all the F genes required for F pilus formation in a yeast GAL4 activation domain vector (pACTII), we transformed yeast containing a plasmid (pAS1CYH2traA) encoding a GAL4 DNA-binding domain-F-pilin fusion. Doubly transformed cells were screened for GAL4-dependent gene expression. This screen repeatedly identified only a single Tra protein, TraQ, previously identified as a likely F-pilin chaperone. The F-pilin-TraQ interaction appeared to be specific, as no transcriptional activation was detected in yeast transformants containing pACTIItraQ plasmids and the Salmonella typhi pED208 traA gene cloned in pAS1CYH2. Two traQ segments isolated in the screen against F-pilin were tested for complementation of a traQ null allele in E. coli. One, lacking the first 11 (of 94) TraQ amino acids, restored DNA donor activity, donor-specific bacteriophage sensitivity and membrane F-pilin accumulation to wild-type levels. The second, lacking the first 21 amino acids, was much less effective in these assays. Both TraQ polypeptides accumulated in E. coli as transmembrane proteins. The longer, biologically active segment was fused to the GAL4 DNA-binding domain gene of pAS1CYH2 and used to screen the tra fragment library. The only positives from this screen identified traA segments. The fusion sites between the traA and GAL4 segments identified the hydrophobic, C-terminal domain IV of F-pilin as sufficient for the interaction. As TraQ is the only Tra protein required for the accumulation of inner membrane F-pilin, the interaction probably reflects a specific, chaperone-like function for TraQ in E. coli. Attempts to isolate an F-pilin-TraQ complex from E. coli were unsuccessful, suggesting that the interaction between the two is normally transient, as expected from previous studies of the kinetics of TraA membrane insertion and processing to F-pilin.

Amino Acid Sequence↗
PubMed1998

Urethral prolapse after collagen injection.

A woman who was treated for intrinsic urethral sphincteric deficiency with periurethral injection of glutaraldehyde cross-linked collagen had prolapse of the urethral mucosa and recurrence of incontinence. She subsequently required surgical resection and a fascia lata sling. This is the first known occurrence of this postinjection complication.

Aged↗
PubMed1998

Urinary incontinence and pelvic organ prolapse in nulliparous women.

OBJECTIVE: To determine differences between vaginally parous and nulliparous women presenting with urinary incontinence and pelvic organ prolapse. METHODS: Seven hundred forty eight consecutive referrals with urinary incontinence or pelvic organ prolapse, 62 of whom were nulliparous, were included in the analysis. Five hundred thirty-seven (72%) had urinary incontinence and 235 (31%) had at least stage III pelvic organ prolapse. Each subject had standard history, physical examination, and multichannel urodynamic testing. Differences between parous and nulliparous women were compared using parametric and nonparametric analysis of variance and the chi2 test with Yates correction where appropriate. RESULTS: The only significant demographic difference between the groups was that parous women had more previous continence and prolapse surgery. There were significant differences in distribution of diagnoses according to parity, with the nulliparas much less likely to have pelvic organ prolapse. Among incontinent women without prolapse, nulliparas were significantly more likely to have pure detrusor instability. Of those with pure genuine stress incontinence, nulliparas were older, had less anterior vaginal wall descent, less bladder neck mobility, narrower genital hiatus and perineal body measurements, and lower maximum urethral closure pressures. Of those with pure detrusor instability, the only difference was that nulliparas were significantly younger. For women with stage III pelvic organ prolapse or worse, no significant difference in any measured characteristic was noted. CONCLUSION: Nulliparous women were less likely to present with pelvic organ prolapse and those with urinary incontinence differed little from incontinent parous women.

Adult↗
PubMed1998

The use of an optical outlining system for weekly on-set verification of patients with carcinoma of the breast.

The installation of an optical outlining system on both a simulator and treatment unit has enabled patient cross-sectional outlines to be measured throughout a radical treatment period of 5 weeks. Two studies were conducted to assess the reproducibility of positioning in treatments for breast carcinoma. The first study assessed changes in outline for 23 patients treated on a home-made tilt-board. Seven patients (32%) displayed a change in shape in excess of 1 cm during the course of treatment, which could have significant dosimetric consequences. The second study focused on the reproducibility of set-up using different tilt-boards. This included a further 19 patients treated using a commercial board, which is now in routine use.

Adenocarcinoma↗
PubMed1997

Pressure transmission ratio reproducibility in stress continent and stress incontinent women.

Our objective was to determine the effect of cough strength on pressure transmission ratios and establish quantitative and qualitative intra-observer test-retest reproducibility of pressure transmission ratios calculated from dynamic urethral pressure profilometry. The study included 242 consecutive urodynamic evaluations on women without pelvic organ prolapse. Dynamic urethral pressure profiles were performed in duplicate with coughs of different intensities. The analysis included pressure transmission ratios from the proximal 3 urethral quartiles (Q1 through Q3) and the mean pressure transmission ratio calculated from these quartiles. The final diagnoses were stratified into genuine stress incontinence, 135 (56%), and stress continence, 107 (44%). Correlations were strong for pressure transmission ratios from the first versus the second dynamic urethral pressure profile (K = 0.712 for mean). While the variation in cough intensity between hard and soft coughs averaged 30 cm H2O (P < 0.001), correlation's were equally strong between hard and soft cough pressure transmission ratios (K = 0.712 for mean). When mean pressure transmission ratios were stratified into below 90% and at least 90% categories, 83.5% of subjects had test-retest concordance (K = 0.671). Concordance rates were less for stress continent subjects (80.0%; K = 0.527) than for genuine stress incontinence subjects (86.4%; K = 0.679). Pressure transmission ratios appear to have reasonable quantitative and qualitative reproducibility which is unaffected by cough strength. The degree of individual variability limits the utility of pressure transmission ratios to diagnose genuine stress incontinence independent of other, equally variable clinical and urodynamic parameters, but this measure is sufficiently reproducible to be useful in characterizing stress sphincteric function in population studies.

Aged↗
PubMed1997

Abdominal sacral colpoperineopexy: a new approach for correction of posterior compartment defects and perineal descent associated with vaginal vault prolapse.

OBJECTIVE: Our purpose was to assess a modification of abdominal sacral colpopexy in 19 patients. STUDY DESIGN: The rectovaginal space was dissected to the superior aspect of the posterior vaginal fascia still contiguous with the perineal body. Mersilene (Ethicon, Somerville, N.J.) mesh was sutured to this fascia and along the entire posterior vaginal wall. Patients with vault prolapse, perineal descent, and associated rectoceles or enteroceles are reported. Outcome measures included bowel symptoms and pelvic organ prolapse staging. Defecography was performed in three patients. Wilcoxon signed rank analysis was used for comparison of prolapse measures. RESULTS: Mean follow-up was 11 weeks. Bowel symptoms improved in 8 of 11 women. No subjects had greater than stage II prolapse postoperatively and median improvement in stage was 3 (range 2 to 4). The mean decrease in the genital hiatus measurement was 3.13 +/- 1.25 (range 2 to 6) cm. Postoperative defecography documented correction of rectoceles and enteroceles and improvement in perineal descent with straining. CONCLUSIONS: Abdominal sacral colpoperineopexy is effective surgery for vaginal vault prolapse associated with perineal descent and posterior vaginal defects.

Adult↗
PubMed1997

The value of intraoperative cystoscopy in urogynecologic and reconstructive pelvic surgery.

OBJECTIVE: Our goal was to evaluate the role of intraoperative cystoscopy during surgery for pelvic organ prolapse and urinary incontinence. STUDY DESIGN: Charts of 224 consecutive patients who had intraoperative cystoscopy performed after urogynecologic surgery were reviewed. RESULTS: Nine injuries occurred that were unsuspected before cystoscopy, for an incidence of 4%. Six ureteral ligations occurred, four after Burch cystourethropexy and two after vaginal culdoplasty. Intravesical sutures were noted after two Burch procedures, and another injury occurred with passage of fascia lata through the bladder during a pubovaginal sling procedure. Eight injuries were managed by removal and replacement of the suture or sling with only one requiring ureteroneocystotomy. When patients with injuries were compared with those without, there were no statistical differences in demographic or surgical parameters. CONCLUSIONS: The potential for damage to the lower urinary tract is significant with complex urogynecologic surgery. Because of the increased and delayed morbidity associated with unrecognized injury, intraoperative surveillance cystoscopy should be considered a part of all such procedures.

Adult↗
PubMed1997

Clinical predictors of urinary incontinence in women.

OBJECTIVE: Our purpose was to characterize historic and clinical parameters in incontinent women to determine the predictive value for urodynamic diagnoses. STUDY DESIGN: The analysis includes 535 consecutive women with final diagnoses of genuine stress incontinence, detrusor instability, or both. Evaluations included a standardized history, examination, urinary diary, quantitation test, and urodynamics. The analysis used one-way analysis of variance, chi 2 analysis with Yates' correction, and Fisher's exact test. RESULTS: A total of 351 (66%) women were diagnosed with genuine stress incontinence, 102 (19%) with detrusor instability, and 82 (15%) with both. Half had symptoms of both stress incontinence and urge incontinence, of whom only 21% had both genuine stress incontinence and detrusor instability. Fewer than half of women diagnosed with genuine stress incontinence or detrusor instability had just symptoms of stress incontinence or urge incontinence, respectively. Evaluation of historic, examination, and urinary diary data for their influences on the predictive value of pure stress incontinence or urge incontinence revealed statistical differences for urethral hypermobility, estrogen deficiency, and incontinent episodes, yet they were not clinically practical predictors. CONCLUSIONS: Pure symptoms identify fewer than half of patients with pure genuine stress incontinence or detrusor instability; historic and clinical parameters do not improve the sensitivity of these symptoms.

Adult↗
PubMed1997

Diagnosing intrinsic sphincteric deficiency: comparing urethral closure pressure, urethral axis, and Valsalva leak point pressures.

OBJECTIVES: Our purpose was to compare three measures proposed to diagnose intrinsic sphincteric deficiency: maximum urethral closure pressure, Valsalva leak point pressure, and straining urethral axis. STUDY DESIGN: A total of 159 women with pure genuine stress incontinence had the three measures determined in a standardized fashion. Critical cutoff values for the Valsalva leak point pressure (52 cm) and urethral axis (22 degrees) were established by examining relative frequency distribution curves, using closure pressure of 20 as the arbitrary benchmark value for the prevalence of intrinsic sphincteric deficiency. The distribution of cutoff values is described and differences among the measures with respect to risk factors for intrinsic sphincteric deficiency and incontinence severity were determined. RESULTS: Half the subjects fell below at least one cutoff value, but only 10% fell below all three. Sixty-four percent of subjects with either low closure pressure or leak point pressure had low values for the other, whereas 21% had discordance between them. Only 53% of subjects with low closure pressure and 40% with low leak point pressure had an axis < or = 22 degrees. Conversely, a substantial portion (36%) of subjects with pure genuine stress incontinence without urethral hypermobility had neither low urethral or leak point pressures. All three cutoff-values were associated with risk factors for intrinsic sphincteric deficiency, but only low closure and leak point pressures had significant associations with the severity of incontinence. CONCLUSIONS: Intrinsic sphincteric deficiency should be diagnosed by a composite of historic, urodynamic, anatomic, and clinical severity criteria. We would include a maximum urethral closure pressure < or = 20, a Valsalva leak point pressure < or = 50, and a stress urethral axis < or = 20 in this composite.

Adolescent↗
PubMed1997

Sacral osteomyelitis: an unusual complication of abdominal sacral colpopexy.

BACKGROUND: Abdominal sacral colpopexy using permanent mesh is an established technique for repair of vaginal vault prolapse. Infection is not a frequent complication. We report two cases of lumbosacral osteomyelitis treated with intravenous antibiotics without mesh removal. CASES: The first patient had known advanced degenerative arthritis. Unremitting severe low back pain 5 years after abdominal sacral colpopexy prompted magnetic resonance imaging (MRI), revealing osteomyelitis and diskitis. The second patient developed symptoms 2 months postoperatively, and MRI indicated osteomyelitis with epidural abscess. Both patients received intravenous antibiotics, and neither required surgical debridement or mesh removal. CONCLUSION: Osteomyelitis can present remote from the operation and can be difficult to diagnose. Protracted parenteral antibiotic therapy can be definitive treatment without mesh removal.

Aged↗
PubMed1997

Uroflowmetry in women with urinary incontinence and pelvic organ prolapse.

OBJECTIVE: To characterize uroflowmetry parameters in women with pelvic organ prolapse (POP) and urinary incontinence (UI) and to assess the effects of clinical and urodynamic variables on these parameters. PATIENTS AND METHODS: The study comprised 655 consecutive women who presented with UI or POP and who had interpretable uroflowmetry values. Normal uroflowmetry values were defined as a maximum flow (Q(max)) > or = 15 mL/s, a mean flow (Q(mean)) > or = 10 mL/s, a post-void residual volume (PVR) < or = 100 mL and a continuous, single-peak waveform. Parametric and non-parametric analysis of variance and chi-square analysis were used to compare differences between diagnostic groups. Multiple linear regression models were developed to evaluate factors considered to influence uroflowmetry. RESULTS: Of the 655 patients, 471 (72%) had UI of whom 16% had pure detrusor instability (DI), 69% pure genuine stress incontinence (GSI) and 15% with both, and 184 (28%) had POP, 26% of whom also had DI. Of all patients, 72% had normal uroflowmetry patterns, 13% had multiple peaks and 15% had patterns with interrupted flow; 56% had completely normal uroflowmetry. There were significant differences in uroflowmetry values between the POP and UI groups, with the former having a lower Q(max) and Q(mean) (P < 0.001), larger PVRs (P < 0.001) and a lower percentage of totally normal uroflowmetry (33% and 64%, respectively, P < 0.001). Of patients with POP, 30% had a PVR > 100 mL. Because of the differences, the POP and UI groups were evaluated separately in the regression analysis. In both groups, the most important determinants of flow rate were the volume voided and pressure transmission ratio (PTR). However, when several factors (including age, voided volume, PTR and maximum detrusor pressure with flow and at Q(max)) were included in the model, they accounted for only 23-26% of the variability of flow in the patients with UI and 36-39% of the variability in patients with POP. The subsets of patients with pure DI in both the UI and POP groups had higher PVR volumes than the other subsets. CONCLUSIONS: These results show that the positive correlation between flow rate and voided volume described in normal populations is also observed in women with UI and POP. However, most of the variability in urine flow was not attributable to factors such as age, voided volume and PTR, confirming the complexity of the micturition mechanism. Women with POP had more objective evidence of emptying-phase dysfunction than women with UI, although most emptied their bladders efficiently. Finally, the results suggest that women with DI exhibit dysfunction of both inhibitory and facilitory detrusor control.

Female↗
PubMed1997

Consistency of patient information ... is this happening?

Most patients attending a hospital appointment are likely to feel at least slightly apprehensive and, therefore, unable to retain all of the information given to them. A patient visiting a department in which they had been diagnosed with cancer that required radiotherapy is perhaps one of the worst case scenarios. Both cancer and radiotherapy are words that create some of the greatest fears for the general public and, even, for members of the health profession. Due to the misconceptions about cancer and radiotherapy, patients require accurate information to help allay some of their fears. At the Department of Radiotherapy and Oncology, Freedom Fields Hospital, Plymouth, it was decided that an audit be used to determine the accuracy and consistency of information delivered within a specialized unit, before this information was disseminated to other departments within the hospital. The goals of the audit were to highlight possible weak areas of advice, to agree on the best information to furnish for a given situation, and to implement distribution of a staff handout to help achieve these aims. Staff members (n = 35) of various professions and levels were asked to complete a questionnaire relating to a patient with carcinoma of the breast undergoing a routine course of radiotherapy. Results of the audit indicated staff vagueness or conflicting responses in certain situations.

Breast Neoplasms↗