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Biomedical subjects

C B Jones

Publications and source records attributed to C B Jones.

At least 19 recordsLinked to original sources
PubMed2001

Percutaneous stabilization of U-shaped sacral fractures using iliosacral screws: technique and early results.

PURPOSE: To present the technique and early results of percutaneous stabilization of U-shaped sacral fractures with attention to neurologic recovery and maintenance of fracture reduction of the sacrum. DESIGN: Retrospective clinical study. SETTING: Level I trauma center. PATIENTS: During a thirty-eight-month period, 442 patients with pelvic ring disruptions were treated at a Level I trauma center. Thirteen (2.9 percent) of these patients had displaced U-shaped sacral fractures treated with percutaneous stabilization. INTERVENTION: Fracture stabilization was accomplished using fluoroscopically guided iliosacral screws inserted percutaneously with the patient positioned supine. Neurodiagnostic monitoring was not used during screw insertions. This technique was limited to patients with sacral kyphotic deformities, which allowed in situ fixation. Sacral neurologic decompression was not performed. MAIN OUTCOME MEASUREMENTS: Fracture healing and the stability of fixation were assessed on inlet and outlet radiographs and a lateral sacral view. Detailed neurologic examinations were performed at injury and at follow-up. RESULTS: The sacral fractures were classified based on plain pelvic radiographs and computed tomography scans and included one Type 1, eight Type 2, and four Type 3 fracture patterns. Twenty-five fully threaded cancellous 7.0-millimeter cannulated screws were used. Eleven patients had bilateral screw fixations; one patient had unilateral double screw fixation; and one patient had unilateral single screw fixation. Operative time for screw insertion averaged forty-eight minutes, with 2.1 minutes of fluoroscopy per screw. Accurate screw insertions without neuroforaminal or sacral spinal canal violations were confirmed in all patients with postoperative pelvic plain radiographs and computed tomography scans. A paradoxical inlet view of the upper sacral segments on the injury anteroposterior pelvis was seen in twelve of thirteen patients (92.3 percent), and the diagnosis was confirmed with the lateral sacral view in all thirteen (100 percent) patients. Preoperatively, sacral kyphosis averaged 29 degrees, whereas postoperative sacral kyphosis averaged 28 degrees. Screw disengagement occurred without a change in position of the sacral fracture in the only patient treated with a single unilateral screw. All fractures healed clinically and radiographically. Of the nine patients with preoperative neurologic abnormalities, two (22 percent) patients had residual neurologic deficits. Both patients had associated multiple level lumbar burst fractures, which required decompression and instrumented stabilization. CONCLUSIONS: These sacral fractures are rare and occur after significant spinal axial loading. A paradoxic inlet view of the upper sacrum on the anteroposterior plain pelvic radiograph heralds the diagnosis. Delayed diagnosis is avoided by a high clinical suspicion, early lateral sacral radiographs, and pelvic computed tomography scans. Surgical stabilization may assist in early mobilization of the patient from recumbency and prevents progressive deformity with associated nerve root injury. Percutaneous fixation diminishes potential blood loss and operative times, yet still allows subsequent sacral decompression of the local neural elements using open techniques when necessary. Early percutaneous iliosacral screw fixation is effective treatment for these injuries.

Adult↗
PubMed2001

Regulation of bleomycin-induced DNA breakage and chromatin structure in lung endothelial cells by integrins and poly(ADP-ribose) polymerase.

Activation of endothelial cell integrins inhibits DNA breakage by diverse agents, including the DNA-damaging agent bleomycin. DNA breaks activate nuclear poly(ADP-ribose) polymerase (PARP), which regulates chromatin structure and DNA repair. We determined the role of PARP in suppression of bleomycin genotoxicity by integrins using wild-type and PARP knockout mouse lung endothelial cells (MLEC), and the PARP inhibitor, 3-aminobenzamide (3AB). Activation of beta1 integrins by antibody clustering enhanced the sensitivity of wild-type nuclei to digestion with micrococcal nuclease and deoxyribonuclease I, indicating that chromatin structure was altered. 3AB blocked this effect. Knockout and 3AB-treated wild-type MLEC were hypersensitive to deoxyribonuclease I compared with wild-type cells, demonstrating that PARP regulates chromatin structure. Integrin clustering reduced the hypersensitivity of knockout cells, suggesting additional, PARP-independent mechanisms that inhibit nuclease interaction with chromatin. Bleomycin caused DNA breakage in wild-type and knockout MLEC. Breaks were eliminated after 60 min incubation of wild-type cells in drug-free medium, whereas 3AB or PARP knockout inhibited DNA repair. Integrin clustering protected wild-type cells from DNA breakage, and 3AB and PARP knockout inhibited this protection. Bleomycin caused large increases in PARP activity in wild-type but not knockout MLEC, and integrin clustering inhibited the activation of PARP. The results indicate that the antigenotoxic effects of integrin activation require PARP and that integrins alter chromatin structure by PARP-dependent and -independent mechanisms.

Animals↗
PubMed2001

Surgical treatment of olecranon fractures.

Fractures of the olecranon are common injuries with no single accepted treatment. Numerous clinical factors and biomechanical studies guide the surgeon in determining a treatment plan. The goals of surgical management include anatomical reduction and stable fixation, which allow early range of motion of the elbow joint. Numerous fixation methods have been described and include screw fixation, cerclage wiring, modified tension-band wiring, and plate fixation. The surgical technique depends on a combination of patient factors, the fracture pattern, and the mechanical stability of the fixation construct. Postoperative rehabilitation includes early active range-of-motion exercises and follows clinical and radiographic healing. Complications are related to the fracture, choice of implant, and surgical technique.

Adolescent↗
PubMed2000

Enhancement of camptothecin-induced cytotoxicity with UCN-01 in breast cancer cells: abrogation of S/G(2) arrest.

PURPOSE: To determine the ability of UCN-01 to abrogate the cell cycle arrest induced by camptothecin (CPT) in tumor cells that lack p53 function, and therefore enhance the cytotoxicity of CPT in these cells in relation to normal cells with wild-type p53. METHODS: The responses of MDA-MB-231 and GI 101A breast cancer cells were compared to those of normal bovine endothelial cells. Cytotoxicity was assessed by the MTT assay, and the resulting data were modeled using median-effect analysis. Inhibition of DNA synthesis was determined by loss of [(3)H]thymidine incorporation, and cell cycle status was determined by flow cytometric analysis of propidium-iodide-stained nuclei. RESULTS: UCN-01, a specific inhibitor of protein kinase C (PKC) presently in clinical trials, abrogated CPT-induced activation of S and G(2) checkpoints in human MDA-MB-231 and GI 101A breast carcinoma cells, both of which are mutants for the p53 gene. This abrogation occurred with the use of sublethal doses (100 nM) of UCN-01 and correlated with the enhancement of CPT-induced cytotoxicity. Median-effect analysis showed that synergistic cytotoxic interactions existed between CPT and UCN-01 against these tumor cells. In normal cells, however, abrogation of the S phase arrest caused accumulation in G(0)/G(1) phase, perhaps by the presence of wild-type p53 activity, with no change in CPT-induced cytotoxicity. CONCLUSION: We have shown previously that the cytotoxicity of CPT is correlated with cell cycle response in normal and tumor cells. Low doses of CPT arrest cells in the G(2)/M phase and inhibit DNA synthesis, but higher doses cause arrest of cells in S phase. Thus modulation of events at the S and G(2) checkpoints may provide an opportunity to enhance CPT-induced cytotoxicity in tumor cells. The results of this study indicate that UCN-01 enhances the progression of tumor cells through S phase thus greatly increasing CPT-induced cytotoxicity. Normal cells, however, are able to arrest in G(0)/G(1) and thus avoid the increased toxicity induced by CPT. Our findings suggest potential usefulness of combining UCN-01 in topoisomerase I inhibitor-based drug therapy for the treatment of breast cancer with a dysfunctional p53 gene.

Alkaloids↗
PubMed2000

UCN-01 and camptothecin induce DNA double-strand breaks in p53 mutant tumor cells, but not in normal or p53 negative epithelial cells.

Previous research has shown synergistic growth inhibition between UCN-01 and camptothecin (CPT) in tumor cells with mutant p53 versus tumor cells with wild-type p53. To determine the possible role of p53 in this drug combination, we tested the hypothesis that the synergistic growth inhibition is due to the absence of p53, and can result from the induction of DNA double-strand breaks (DSBs). Experiments were performed with the use of normal human mammary epithelial cells (HMEC); HMEC transfected with HPV16 E6 protein which inactivates p53 (HE6), or p53-mutant MDA-MB-231 tumor cells. CPT, UCN-01, or a 1:1 combination of both, in either HMEC or HE6 cells did not induce DSBs. In contrast, simultaneous treatment of MDA-MB-231 cells with both UCN-01 and CPT induced significant levels of DSBs while treatment with either drug alone did not. While UCN-01 was surprisingly potent against HMEC, the growth inhibition was only additive between UCN-01 and CPT against these cells. HE6 cells were much less sensitive than HMEC to UCN-01 and slightly less sensitive to the combined treatment with UCN-01 and CPT. The drug combination was synergistic against HE6 cells, due to their lower sensitivity to UCN-01. Unlike what was observed previously in MDA-MB-231 cells, UCN-01 did not abrogate CPT-induced inhibition of DNA synthesis in either HMEC or HE6 cells. These data indicate that synergistic growth inhibition by UCN-01 and CPT against p53 mutant MDA-MB-231 tumor cells may be due to induction of DSBs however the loss of p53 function alone does not sensitize normal cells to the combination of both drugs.

Adenocarcinoma↗
PubMed1999

Antiangiogenic potential of camptothecin and topotecan.

PURPOSE: To determine the inhibitory nature of sublethal doses of camptothecin (CPT) and topotecan (TPT) treatments on normal human endothelial cells in vitro, as well as the in vivo antiangiogenic activity as compared to another antiangiogenic compound, TNP-470 and to a nonspecific cytotoxic agent, cisplatin. METHODS: Growth inhibition was determined by the crystal violet assay to measure relative cell numbers. (3)H-thymidine uptake was used to determine the inhibitory effect of CPT and TPT on DNA synthesis in vitro. Cell viability was determined using trypan blue exclusion assays. Cell cycle response to CPT was determined by flow cytometric analysis of propidium iodide-stained nuclei. In vivo inhibition of angiogenesis was determined by the disc angiogenesis system (DAS), where surgical sponge discs were placed subcutaneously in the rat dorsum and the ability of systemic treatment with liposomal CPT (LCPT), TPT, TNP-470 or cisplatin to inhibit vascular growth into the discs was evaluated. Quantitation of vascular growth was determined using toluidine blue staining of sectioned discs followed by digital image analysis. RESULTS: Treatment with 50 nM CPT or TPT inhibited human umbilical venular endothelial cell (HUVEC) growth as shown by crystal violet staining, but was not cytotoxic to the cells. This was evidenced by the fact that cell numbers did not increase or decrease with treatment, but remained static while cells were viable for over 96 h posttreatment. (3)H-thymidine uptake in HUVEC was inhibited as early as 5 min, reached a maximum inhibition at 24 h and lasted over 96 h posttreatment. Cell cycle analysis of CPT-treated HUVEC showed arrest in S-phase at 12 h with a concurrent decrease in population of cells in G(1). Accumulation of cells at the G(2)/M-phase was discernible at 24 h along with the S-phase inhibition. Treatment of rats with 1 mg/kg LCPT or TPT every other day for 14 days resulted in approximately 30% inhibition of vascular growth into the discs. This inhibition was similar to the inhibition seen with TNP-470, an established and potent angiogenic inhibitor. In contrast, cisplatin was not as effective in inhibiting vascular growth into the discs. CONCLUSIONS: In this work we showed that CPT and TPT inhibit human endothelial cell growth in vitro in a non-cytotoxic manner and that this inhibition lasts more than 96 h after drug removal. We also showed that LCPT and TPT, unlike a nonspecific cytotoxic agent, cisplatin, are as effective as TNP-470 in inhibiting angiogenic growth in the in vivo disc angiogenesis model. From this observation we propose that in addition to their proven tumoricidal activities, camptothecins may have an indirect in vivo antitumor effect mediated through the inhibition of angiogenesis.

Angiogenesis Inhibitors↗
PubMed1998

Displaced avulsion of the ischial apophysis: a hamstring injury requiring internal fixation.

A case is reported of an adolescent sprinter who was chronically disabled by pain after non-operative management for an acute hamstring injury. He had sustained an avulsion fracture of the ischial apophysis with displacement of 2.5 cm. Avulsion fractures of the ischial apophysis with displacement of 2 cm or more are unusual, but they frequently result in a symptomatic non-union, and early diagnosis, open reduction, and internal fixation is to be encouraged.

Acute Disease↗
PubMed1997

Sensitivity to camptothecin of human breast carcinoma and normal endothelial cells.

PURPOSE: To assess parameters that might determine resistance to the topoisomerase I inhibitor, camptothecin (CPT), the sensitivities of three established human breast cancer cell lines (ER-) and of normal bovine endothelial cells to CPT in the free form and incorporated into liposomes (LCPT), were contrasted with topoisomerase I (topo I) content and activity, and with cell cycle response to CPT treatment. METHODS: Drug sensitivities were determined using the tetrazolium dye assay and by 3H-thymidine incorporation. Topo I levels were determined by Western blot analysis, and catalytic activity was determined with a plasmid relaxation assay, using nuclear protein from each cell line. CPT stabilization of cleavable complexes in nuclear extracts was determined using a labeled oligonucleotide with a specific topo I cleavage site. Cell cycle response to CPT was determined by flow cytometric analysis of propidium iodide-stained nuclei. RESULTS: CPT was extremely potent against MDA-MB-157 cells with an IC50 value of 7 nM compared with IC50 values of 150 nM for GI 101A and 250 nM for MDA-MB-231 cells. In contrast, CPT inhibited the incorporation of 3H-thymidine at very low doses in GI 101A and MDA-MB-231 cells with IC50 values of 9 nM and 5 nM, respectively; while MDA-MB-157 cells did not stop incorporating 3H-thymidine until very high doses (500 nM) of CPT were used. When incorporated into multilamellar liposomes (LCPT), CPT retained its potency, with IC50 values similar to that of the free drug. No correlation was found between CPT-induced cytotoxicity and any of the topo I parameters determined. Cell cycle analysis, however, showed an accumulation of cells in G2/M phase after 24 h treatment with low doses (5 nM) of CPT in only GI 101A and MDA-MB-231 cells with no arrest in normal endothelial or MDA-MB-157 cells. At higher doses (50 nM), however, a dramatic accumulation of cells in the S phase was observed in MDA-MB-157, MDA-MB-231 and GI 101A cells. In contrast, a G2/M phase block was seen with the normal bovine endothelial cells using the higher doses of CPT. CONCLUSIONS: The results suggest that cell cycle regulation plays an important role in determining the effect of CPT on malignant and normal cells. The possible mechanisms explaining the sensitivities of the two cellular compartments to the action of CPT are discussed.

Animals↗
PubMed1997

An audit of hospital mortality after urgent and emergency surgery in the elderly.

An audit was carried out of 102 patients aged over 75 years undergoing urgent or emergency surgery in a district general hospital. The risk of death in hospital after general surgery (13 deaths in 49 patients) was greater than after orthopaedic surgery (two deaths in 53 patients) (P < 0.05). In particular, laparotomy carried a high in-hospital mortality: 12 of 25 patients undergoing laparotomy died. Risk of death after general surgery increased with increasing preoperative ASA class, increasing medical risk factors and duration of operation. Orthopaedic cases were fitter than the general surgical cases as determined by ASA class and the number of medical risk factors. NCEPOD has recommended increased involvement of senior medical staff in operations, reduced night-time operating and avoidance of futile surgery. A high proportion of cases were operated on and anaesthetised by higher specialist trainees and consultants. Death rate was not affected by the seniority of doctors involved, nor by the time of day the operation took place. General surgical deaths were predictable postoperatively in most cases, but preoperative prediction of outcome was not specific enough to alter management.

Aged↗
PubMed1996

Synthesis, structure-activity relationships, and pharmacokinetic properties of dihydroorotate dehydrogenase inhibitors: 2-cyano-3-cyclopropyl-3-hydroxy-N-[3'-methyl-4'-(trifluoromethyl)phenyl ] propenamide and related compounds.

The active metabolite (2) of the novel immunosuppressive agent leflunomide (1) has been shown to inhibit the enzyme dihydroorotate dehydrogenase (DHODH). This enzyme catalyzes the fourth step in de novo pyrimidine biosynthesis. A series of analogues of the active metabolite 2 have been synthesized. Their in vivo biological activity determined in rat and mouse delayed type hypersensitivity has been found to correlate well with their in vitro DHODH potency. The most promising compound (3) has shown activity in rat and mouse collagen (II)-induced arthritis models (ED50 = 2 and 31 mg/kg, respectively) and has shown a shorter half-life in man when compared with leflunomide. Clinical studies in rheumatoid arthritis are in progress.

Acrylamides↗
PubMed1996

The nursing practice environment, staff retention, and quality of care.

The effects of key factors in the nursing practice environment--management style, group cohesion, job stress, organizational job satisfaction, and professional job satisfaction--on staff nurse retention and process aspects of quality of care were examined. Hinshaw and Atwood's (1985) anticipated turnover model was modified and expanded to include relevant antecedent and outcome variables. The four-stage theoretical model was tested using data from 50 nursing units at four acute care hospitals in the southeast. The model explained 49% of the variance in staff nurse retention and 39% of the variance in process aspects of quality of nursing care. Study findings warrant careful consideration in light of recent practice environment changes: experience on the unit and professional job satisfaction were predictors of staff nurse retention; job stress and clinical service were predictors of quality of care. The variable contributing the most to indirect, and in turn, total model effects, was that of management style. These results substantiate the belief that aspects of the practice environment affect staff nurse retention, and most importantly, the quality of care delivered on hospital nursing units.

Analysis of Variance↗
PubMed1996

Ventilator-associated pneumonia due to Pseudomonas aeruginosa.

OBJECTIVE: Ventilator-associated pneumonia (VAP) caused by Pseudomonas aeruginosa has been associated with higher case fatality rates than VAP caused by other bacterial etiologies. The causes of this excess mortality are unclear. DESIGN: Retrospective review of 38 consecutive ventilated patients with Pseudomonas pneumonia, documented by highly reliable methods. Charts of five additional patients were unavailable for review. SETTING: Medical ICUs of a university-affiliated Veterans Affairs Medical Center and a university-affiliated municipal hospital. MEASUREMENTS: Prospectively collected hospital admission acute physiologic and chronic health examination (APACHE) II scores and cause of ICU admission. Retrospectively calculated organ failure and APACHE scores, VAP score. Clinical and microbiologic variables. Antibiotic treatment and outcome. Direct cause of death by standard definitions. RESULTS: Overall mortality was 69% (26/38), significantly higher than the APACHE II predicted mortality of 42.6% (p=0.037). At least 38% (10/26) of deaths were directly attributable to Pseudomonas VAP. Multivariate analysis of factors associated with death found infectious cause for ICU admission (odds ratio [OR]=8.67; 95% confidence interval [CI], 0.86 to 85.94) and number of organ dysfunctions on the day of diagnosis (OR=1.73, 95% CI, 1.02 to 2.92) were significant. Septic shock from Pseudomonas VAP, septic shock from subsequent infection, and multiple organ dysfunction syndrome were the most common immediate causes of death. Mortality increased linearly with increasing APACHE III score on the day of diagnosis. Of initial antibiotic regimens, 67% (26/36) were considered failures. Persistent pneumonia occurred in 35% of patients while recurrent pneumonia was unusual (1/38). CONCLUSIONS: Development of Pseudomonas pneumonia results in a mortality rate in excess of that due to the presenting illness. The attributable mortality determined by several means appears to approach 40%. The excess mortality appears to be related to the host defense response to the pneumonia rather than any characteristic of the pneumonia. Even standard antibiotic regimens fail frequently and do not prevent the excess mortality. Since at least 38% of deaths can be directly attributable to the Pseudomonas pneumonia, improvement in therapy is needed.

APACHE↗
PubMed1996

Hydroxylation of lauramide diethanolamine by liver microsomes.

Lauramide diethanolamine (LDEA)--a compound used in cosmetics and soap products as an emollient, thickener, and foam stabilizer--was observed to be metabolized by rat liver microsomes to two major products that were identified by GC/MS to be the 11-hydroxy and 12-hydroxy derivatives of LDEA. The specific activities for LDEA 11- and 12-hydroxylation in microsomes prepared from control rats were 2.23 +/- 0.40 and 0.71 +/- 0.17 nmol/min/mg protein, respectively. Treatment of rats with the cytochrome P4504A inducer and peroxisome proliferator, diethylhexyl phthalate, increased the LDEA 12-hydroxylation rate to 3.50 +/- 0.48 nmol/min/mg protein, a 5-fold increase in specific activity, whereas the LDEA 11-hydroxylase activity remained unchanged. Because LDEA contains a 12-carbon side chain, LDEA hydroxylation rates were compared with the hydroxylation rates for lauric acid. The specific activities of lauric acid 11- and 12-hydroxylation reactions in diethylhexyl phthalate-treated rats were 1.7-fold and 3.2-fold greater than the LDEA 11- and 12-hydroxylation rates, respectively. When LDEA hydroxylation reactions were performed in the presence of a polyclonal antibody to the rat P4504A forms, formation of 12-hydroxy-LDEA was inhibited by 80%. Rat kidney microsomes also supported the hydroxylation of LDEA at its 11- and 12-carbon atoms, with specific activities of 0.05 +/- 0.01 and 0.28 +/- 0.02 nmol/min/mg protein, respectively. LDEA was also metabolized to 11- and 12-hydroxy derivatives by human liver microsomes at specific activities of 0.22 +/- 0.06 and 0.84 +/- 0.26 nmol/min/mg protein, respectively.

Animals↗
PubMed1996

Registered nurse turnover and the changing health care system.

Changes in health care delivery and cyclic fluctuations in the registered nurse (RN) labor market affect health care costs, access, and quality. This study provides insight into one factor central to these issues, the job-change behavior of RNs. The theory of human capital provides the foundation to guide investigation, and econometric modeling is used to explore relationships among study variables. Model results show clear differences in job change behavior of nurses employed in hospital and nonhospital settings. These differences are a reflection, not only of individual nurse preferences, but also of wages, working conditions, and opportunities associated with various health care settings. Understanding these relationships is essential to leaders in the nursing profession as they plan for and respond to changes in health care delivery.

Adult↗
PubMed1995

Ventilator-associated Pseudomonas aeruginosa pneumonia: radiographic findings.

PURPOSE: To characterize the radiographic features of ventilator-associated Pseudomonas aeruginosa pneumonia (PAP). MATERIALS AND METHODS: In 56 patients (40 men and 16 women), PAP was documented with fiberoptic bronchoscopy. All patients underwent mechanical ventilation for at least 48 hours before diagnosis. The findings on chest radiographs were recorded. In eight patients in whom computed tomography (CT) was performed, results were compared with radiographic findings. RESULTS: Twenty-six patients with adult respiratory distress syndrome (ARDS) had diffuse bilateral confluent opacities; 30 patients without ARDS had multifocal opacities. In 13 patients, cavities were detected at chest radiography, CT, or both. Seven of 29 patients with pleural abnormalities had empyema. CT provided important additional information (presence of cavities or effusions) in four cases. CONCLUSION: Findings on chest radiographs are nonspecific for PAP. The frequencies of cavities and empyema are surprisingly low, perhaps owing to prompt diagnosis and therapy.

Bronchoscopy↗