Biomedical subjects

John L Clayton

Publications and source records attributed to John L Clayton.

10 recordsLinked to original sources

PubMed2006

Pelvic fractures in children.

Although rare, pelvic fractures in children have significant morbidity and mortality. No specific guidelines have been developed for the management of these injuries. We reviewed all trauma patients of age 16 years or younger with pelvic fractures treated at our Level I trauma center over the past 12 years. Of 1008 patients with pelvic fractures, 74 were children. Early hemodynamic instability was seen in 14 per cent of cases. Blood transfusions were required in 26 per cent of cases, angiography in 3 per cent of cases, operations for associated injuries in 46 per cent of cases, operative pelvic fracture fixation in 18 per cent of cases, and intensive care unit care in 58 per cent of cases. Mortality was 5 per cent, mostly from hemorrhage and multiple complex injuries. We conclude that pelvic fractures in children are associated with a high frequency of pelvic bleeding and associated injuries that often require operative interventions and intensive care unit care.

Adolescent↗

PubMed2005

High body mass index and short- and long-term renal allograft survival in adults.

BACKGROUND: The effect of recipient obesity on kidney allograft survival remains enigmatic. The purpose of this study was to evaluate the effect of donor and recipient body mass index on graft survival. METHODS: Retrospective study of 193 consecutive, adult renal transplants, with at least six months follow-up (mean 24+/-14.1 months). Patients were divided into two groups based upon body mass index (BMI), [weight (kg)/height (m)]: normal (<30.0, n=137) and obese (> or =30.0, n=56). Endpoints were graft loss, defined as either total loss of graft function (return to dialysis) or patient death with a functional graft. Unadjusted and adjusted multivariate analysis techniques, including Kaplan-Meier and Cox proportional hazards regression were used. RESULTS.: Individuals with a BMI > or =30 were not more likely to experience graft loss (O.R. 0.93, 95% C.I. 0.50, 1.72). Rates of acute rejection were not increased in obese recipients. While mortality was not increased in the BMI > 30 group, morbidity, especially surgical, had an increased incidence. The ratio of recipient to donor BMI did not influence graft survival. CONCLUSION: Obese recipients (BMI > or =30.0) were not at increased risk for graft failure. Additionally, matching donor and recipient BMI's would not appear to substantially improve transplant outcome. Obese recipients do have increased posttransplant morbidity and risk all the known health consequences associated with obesity. Careful evaluation and clinical management of obese patients allows for successful kidney transplantation with results equivalent to normal BMI patients.

Body Mass Index↗

PubMed2005

Multicenter construct validity for southwestern laparoscopic videotrainer stations.

BACKGROUND: The "Southwestern" videotrainer stations have demonstrated concurrent validity (transferability to the operating room). The purpose of this study was to evaluate the Southwestern stations for construct validity (the ability to discriminate between subjects at different levels of experience). MATERIALS AND METHODS: From two surgical training programs, Institutional Review Board approved protocol data were collected from 142 subjects, including novice (medical students and R1, n = 66), intermediate (R2-R4, n = 67), and advanced (R5 and expert surgeons, n = 9) groups. All participants performed three repetitions on each of five stations. Completion time was scored for each task. Laparoscopic experience was determined from residency case log databases and from expert surgeon personal case logs. Results for the three groups were compared using one-way ANOVA, including relevant pair-wise comparisons. Correlations between number of laparoscopic cases performed and task scores were determined by Pearson's and Spearman's rho-correlation coefficients. RESULTS: The mean number of laparoscopic cases performed prior to completing the five tasks was 0 for novices, 9 for intermediates, and 431 for the advanced group. Significant differences (P < 0.001) were noted between groups for all five tasks and composite score. Task scores and composite scores significantly correlated with laparoscopic experience (P < 0.01). CONCLUSION: These data suggest that differences in laparoscopic ability are detected by performance on the videotrainer; thus, construct validity is demonstrated. Moreover, scores accurately reflect laparoscopic experience. Further validation may allow such simulators to be used for testing and credentialing purposes.

Adult↗

PubMed2004

Clinical outcomes and disease progression among patients coinfected with HIV and human T lymphotropic virus types 1 and 2.

The goal of this study was to investigate clinical outcomes and survival probabilities among persons coinfected with human immunodeficiency virus (HIV) and human T lymphotropic viruses types 1 and 2 (HTLV-I/II). A nonconcurrent cohort study of 1033 HIV-infected individuals was also conducted. Sixty-two patients were coinfected with HTLV-I, and 141 patients were coinfected with HTLV-II. HTLV-I/II coinfection was highly associated with African-American race/ethnicity, age of >36 years, higher CD4(+) T cell count at baseline and over time, and history of injection drug use. Coinfected patients were more likely to have neurologic complications, thrombocytopenia, respiratory and urinary tract infections, and hepatitis C. Despite having higher CD4(+) T cell counts over time, there was no difference in the incidence of opportunistic infections. Progression to both acquired immunodeficiency syndrome (AIDS; adjusted hazard ratio [aHR], 0.50; 95% confidence interval [CI], 0.25-0.98) and death (aHR, 0.57, 95% CI, 0.37-0.89) were slower among HTLV-II-coinfected patients, compared with time-entry- and CD4(+) T cell count-matched control subjects. In conclusion, HIV-HTLV-I/II coinfection may result in improved survival and delayed progression to AIDS, but this happens at the expense of an increased frequency of other of clinical complications.

AIDS-Related Opportunistic Infections↗

PubMed2004

Regulation of estrogen-mediated cell survival and proliferation by p160 coactivators.

BACKGROUND: Estrogen receptor (ER) activity is dependent on coactivator (CoA) proteins. The role of CoA-ER interactions in breast cancer apoptosis remains unexplored. METHODS: Expression vectors for the p160 CoA genes NCOA-1, NCOA-2, or NCOA-3 were transiently transfected into MCF-7 cells. Cell survival was determined by viability and clonogenic survival assays. Effects of CoA expression on estrogen (E2) signaling were determined by estrogen response element (ERE)-luciferase reporter-gene assay. Clonogenic and reporter-gene survival assays were used to examine the molecular inhibition of CoA function (dominant inhibitory [DI]-decoy-CoA) on cell survival. Statistical significance was established at the P < .05 level. RESULTS: Overexpression of NCOA-1, NCOA-2, and NCOA-3 enhanced E2-mediated gene expression by 3.17 +/- 0.51-, 2.33 +/- 0.8-, and 3.65 +/- 0.65-fold, respectively, and enhanced cell survival by suppressing tumor necrosis factor alpha (TNF-alpha)-induced cell death from 80.23% +/- 2.66% viability to 101.5% +/- 8.9%, 86.9% +/- 9.9%, and 95.7% +/- 8.5% viability, respectively. NCOA-1 enhancement of cell survival occurred via suppression of TNF-alpha-induced apoptosis as confirmed by viability and morphologic evaluation. Clonogenic survival and E2-stimulated colony formation in MCF-7 cells were suppressed by expression of DI-decoy-NCOA-1 and DI-decoy-NCOA-3 to 34.4% +/- 7.4% and 54% +/- 5.4% of vector control, but not DI-decoy-NCOA-2. CONCLUSIONS: Overexpression of NCOA-1 and NCOA-3 exerted potent survival effects in breast carcinoma cells. Use of DI-CoA constructs enhanced TNF-alpha-induced cell death and abrogated E2-induced survival. Inhibition of CoA proteins represents a mechanism for enhancing sensitivity therapies in breast carcinoma.

Acetyltransferases↗

PubMed2004

Sensitization of apoptotically-resistant breast carcinoma cells to TNF and TRAIL by inhibition of p38 mitogen-activated protein kinase signaling.

The mitogen-activated protein kinase (MAPK) cascade is a critical component in the regulation of cell survival and proliferation decisions. In breast carcinoma cells, activation of the p38-MAPK member of this family occurs in response to pro-inflammatory cytokines and cellular stress. The involvement of p38-MAPK in the activation of the transcription factor, NF-kappaB, suggests a potential role and mechanism for regulation of cell survival and drug resistance. Generation of the resistant MCF-7 variant (MCF-7TN-R) was achieved by prolonged exposure of MCF-7N cells to increasing concentrations of TNF. Differences in MAPK activation and function in the MCF-7 cell variants were determined. The role of the p38-MAPK pathway in regulation of resistance was determined using pharmacological (SB 203580) or molecular [Dominant Inhibitory (DI)-p38] inhibition. The effect of p38 inhibition on NF-kappaB transcriptional activation was analyzed. As compared to the sensitive MCF-7N parent cell line, the MCF-7TN-R cell line displayed significant resistance to TNF- and TRAIL-induced cell death. Analysis of the expression and phosphorylation of members of the MAPK family revealed an increased basal activation of p38 in the MCF-7TN-R variant. The p38-mediated phosphorylation and transcriptional activity were suppressed by pharmacologic inhibition with SB 230580. Treatment of MCF-7TN-R cells with SB partially restored sensitivity to TNF-induced cell death. In addition, use of a DI-p38 construct with or without the addition to TNF induced cell death, thus restoring TNF-sensitivity to these cells. The ability of p38 inhibition to restore apoptotic sensitivity was correlated with suppression of the TNF-induced cell survival pathway, NF-kappaB. The increased activation of p38-MAPK in MCF-7TN-R cells demonstrates that this signaling pathway through activation of NF-kappaB is an important route for control of resistance to cell death in breast carcinoma. Molecular and pharmacological inhibition of p38-MAPK signaling may represent a mechanism for sensitizing cancer cells to chemotherapeutic regimens and restoration of apoptotic signaling.

Apoptosis↗

PubMed2002

Morphologic and clinical significance of multifocal prostate cancers in radical prostatectomy specimens.

OBJECTIVES: To examine the histologic details of small, independent cancers compared with the largest (index) tumor and their impact on prostate-specific antigen (PSA) failure in 486 men treated only by radical retropubic prostatectomy (RRP). METHODS: The tumor volume and percentage of Gleason grade 4/5 carcinoma were recorded in 3-mm step sections. Univariate statistics were calculated for the largest, total (largest plus smaller cancers), and smaller tumor volumes, number of independent foci, patient age, and follow-up. Cox hazards model determined the relative importance of all variables in relation to failure. RESULTS: The mean index tumor volume was 4.16 cm3; smaller cancer volumes averaged 0.63 cm3. The index cancer volume was gaussian in distribution; smaller tumor volumes were highly skewed toward 234 carcinomas less than 0.5 cm3. Only 17% of all cases had one carcinoma. The Cox model showed similar hazard rates of PSA failure for both the index (3.43) and the total cancer (3.74) volumes. The hazard rate for the presence of any Gleason grade 4/5 carcinoma was 6.5. As the numbers of smaller tumors increased, the PSA cure rates improved. CONCLUSIONS: The PSA failure rates (hazard ratios) were similar for the index tumor and the index plus smaller cancers, confirming that predictive estimates only need to measure the largest carcinoma. The greater the number of lesser cancers, the smaller the size of the index cancer. The extraordinary multiplicity of these small independent cancers in 3-mm step sections may explain the poor correlation between six or more biopsies with the index cancer in radical prostatectomy specimens.

Aged↗

PubMed2002

Identification of mitogen-activated protein kinase kinase as a chemoresistant pathway in MCF-7 cells by using gene expression microarray.

BACKGROUND: Components of the mitogen-activated protein kinase (MAPK) cascade have been implicated in apoptotic regulation. This study used gene expression profiling analysis to identify and implicate mitogen-activated protein kinase kinase (MEK5)-BMK1 (big mitogen-activated kinase-1)/extracellular signal related protein kinase (ERK5) pathway as a novel target involved in chemoresistance. METHODS: Differential gene expression between apoptotically sensitive (APO+) and apoptotically resistant (APO-) MCF-7 cell variants was determined by using microarray and confirmed by reverse transcriptase- polymerase chain reaction (RT-PCR). An apoptotic/viability reporter gene assay was used to deter-mine the effects of the transfection of a dominant-negative mutant of BMK1 (BMK1/DN) in conjunction with apoptotic-inducing agents (etoposide, tumor necrosis factor-alpha [TNF], or TNF-related apoptosis-inducing ligand [TRAIL]), with or without phorbol ester (PMA). RESULTS: Of the 1186 genes detected through microarray analysis, MEK5 was increased 22-fold in APO- cells. Overexpression of MEK5 was confirmed by using RT-PCR analysis. Expression of BMK1/DN alone resulted in a dose-dependent increase in cell death versus control (P <.05). In addition, BMK1/DN enhanced the sensitivity of MCF-7 cells to treatment-induced cell death (P <.05). The ability of PMA to partially suppress TRAIL- and TNF-induced cell death was inhibited by BMK1/DN. However, only TRAIL-induced activity suppression reached statistical significance (P <.05). CONCLUSIONS: The overexpression of MEK5 in APO- MCF-7 breast carcinoma cells shows that this MAPK signaling protein represents a potent survival molecule. Molecular inhibition of MEK5 signaling may represent a mechanism for sensitizing cancer cells to chemotherapeutic regimens.

Antineoplastic Agents↗

PubMed2002

Older partners not associated with recurrence among female teenagers infected with Chlamydia trachomatis.

BACKGROUND: Chlamydia trachomatis-infected female teenagers with older partners may be less likely to discuss the infection with their partner(s) and to use condoms and therefore may be more likely to get reinfected. GOAL: To determine if C trachomatis-infected female teenagers with older partners were more likely to be reinfected than those with same-aged partners. STUDY DESIGN: Females aged 14 years to 18 years who had uncomplicated chlamydial infection, were nonpregnant, attended clinics in five United States cities from June 1995 to May 1997, completed treatment, and resumed sexual activity were observed at 1 and 4 months for interim history and retesting. RESULTS: Of 225 women studied, 73.3% were black, 34.5% had at least one partner who was 3 or more years older during follow-up, 51.6% reported using a condom at the last sex act with all partners, 13.8% had a recurrent infection, and 47.4% reported they were certain that all of their baseline partners were treated. Partner age was not associated with condom use, certainty of partners' taking medication, or recurrent infections after adjustment for visit. CONCLUSIONS: Older partners, accounting for approximately one third of all partners, did not increase the risk of reinfection. Given the high risk for recurrence, follow-up testing and enhanced efforts to ensure partner treatment are appropriate for all young women with chlamydial infections.

Adolescent↗

PubMed2002

Detection of human papillomavirus DNA in urine specimens from human immunodeficiency virus-positive women.

Human immunodeficiency virus (HIV)-positive women may represent one of the fastest-growing populations at risk for acquiring cervical cancer and thus require frequent screening. The purpose of the present studies was to validate a PCR-based urine assay by comparing detection and genotyping of human papillomavirus (HPV) DNA in urine samples and matching cervical swab specimens of HIV-positive women. Despite a difference in amplifiability, the prevalence of any HPV genotype (58% for the cervical swab specimens and 48% for the urine specimens) was not significantly different in this population. The levels of concordance were 70, 71, and 78% for detection of any HPV type, any high-risk HPV type, or any low-risk HPV type in the two specimen types, respectively. While instances of discordant detection were greater for the cervical swab specimens than for the urine specimens, this was not statistically significant. The distributions of HPV genotypes were similar in the cervix and the urine for the majority of types examined. Importantly, detection of HPV DNA in urine was associated with an abnormal Papanicolaou smear to the same extent that detection of HPV DNA in a cervical swab specimen was. These data provide preliminary support for the proposal to use urine testing as a primary or secondary screening tool for cervical cancer in HIV-positive women or as an epidemiological tool. Additional studies with larger sample sizes must be conducted in order to further verify these findings.

Adult↗