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Biomedical subjects

Robert Jones

Publications and source records attributed to Robert Jones.

At least 19 recordsLinked to original sources

12-month follow-up analysis of a multicenter, randomized, prospective trial in de novo liver transplant recipients (LIS2T) comparing cyclosporine microemulsion (C2 monitoring) and tacrolimus.

The LIS2T study was an open-label, multicenter study in which recipients of a primary liver transplant were randomized to cyclosporine microemulsion (CsA-ME) (Neoral) (n = 250) (monitoring of blood concentration at 2 hours postdose) C2 or tacrolimus (n = 245) (monitoring of trough drug blood level [predose]) C0 to compare efficacy and safety at 3 and 6 months and to evaluate patient status at 12 months. All patients received steroids with or without azathioprine. At 12 months, 85% of CsA-ME patients and 86% of tacrolimus patients survived with a functioning graft (P not significant). Efficacy was similar in deceased- and living-donor recipients. Significantly fewer hepatitis C-positive patients died or lost their graft by 12 months with CsA-ME (5/88, 6%) than with tacrolimus (14/85, 16%) (P < 0.03). Recurrence of hepatitis C virus in liver grafts was similar in each group. Based on biopsies driven by clinical events, the mean time to histological diagnosis of hepatitis C virus recurrence was significantly longer with CsA-ME (100 +/- 50 days) than with tacrolimus (70 +/- 40 days) (P < 0.05). Median serum creatinine at 12 months was 106 mumol/L with CsA-ME and with tacrolimus. More patients who were nondiabetic at baseline received antihyperglycemic therapy in the tacrolimus group at 12 months (13% vs. 5%, P < 0.01). Of patients who were diabetic at baseline, more tacrolimus-treated individuals required anti-diabetic treatment at 12 months (70% vs. 49%, P = 0.02). Treatment for de novo or preexisting hypertension or hyperlipidemia was similar in both groups. In conclusion, the efficacy of CsA-ME monitored by blood concentration at 2 hours postdose and tacrolimus in liver transplant patients is equivalent to 12 months, and renal function is similar. More patients required antidiabetic therapy with tacrolimus regardless of diabetic status at baseline.

Age Distribution↗

Male-to-female transsexualism: laparoscopic pelvic floor repair of prolapsed neovagina.

The incidence of prolapse of the neovagina after male-to-female gender reassignment surgery is unknown. We present the first case of laparoscopic total pelvic floor repair in a male-to-female transsexual. This surgical procedure combined an understanding of the anatomy of the male pelvis with the principles of laparoscopic pelvic floor repair in the XX female.

Adult↗

Effect of sildenafil citrate and a nitric oxide donating sildenafil derivative, NCX 911, on cavernosal relaxation and superoxide formation in hypercholesterolaemic rabbits.

Hypercholesterolaemia promotes erectile dysfunction through increased superoxide formation and negation of nitric oxide (NO) bioactivity in cavernosal tissue. The source of superoxide has not been clearly defined, however. Sildenafil (Viagra), the standard therapy for erectile dysfunction, may also be rendered more effective by the presence of an NO donor. One drug that intrinsically fulfils this criterion is sildenafil nitrate (NCX 911), an NO donating derivative of sildenafil. The objective of this study, therefore, was to determine the source of superoxide and its effect on erectile function in corpus cavernosum from hypercholesterolaemic rabbits and to determine whether NCX 911 confers an improvement over sildenafil citrate in this model. Hypercholesterolaemia elicited an increase in superoxide formation by rabbit cavernosal tissue and a reduction of carbachol-stimulated relaxation both of which were reversed by diphenylene iodonium chloride and apocynin (NADPH oxidase inhibitors). In response to sodium nitroprusside, hypercholesterolaemia also caused an attenuation of cavernosal relaxation which was not reversed with NADPH oxidase inhibitors. Both sildenafil citrate and NCX 911 significantly reversed impaired carbachol-stimulated relaxation and inhibited superoxide formation by cavernosal tissue from hypercholesterolaemic rabbits, NCX 911 being more potent. NCX 911 also augmented cavernosal cGMP levels, an effect blocked by the guanylyl cyclase inhibitor, 1H-{1,2,4}oxadiazolo {4,3-a}quinoxalin-1-one (ODQ). These data demonstrate that hypercholesterolaemia promotes erectile dysfunction through an augmentation of superoxide derived from NADPH oxidase in cavernosal tissue. It also indicates that NO donating sildenafil may be therapeutically more beneficial than conventional sildenafil in treating erectile dysfunction with an oxidative stress-related aetiology.

Acetophenones↗

A phase I trial of humanized monoclonal antibody A33 in patients with colorectal carcinoma: biodistribution, pharmacokinetics, and quantitative tumor uptake.

PURPOSE: To determine the in vivo characteristics of huA33, a CDR-grafted humanized antibody against the A33 antigen, we have conducted an open-label, dose escalation, biopsy-based phase I trial of huA33 in patients with colorectal carcinoma. EXPERIMENTAL DESIGN: Patients with colorectal carcinoma were infused with [131I]huA33 (400 MBq: 10 mCi) and [125I]huA33 (40 MBq: 1 mCi) 1 week before surgery. There were four huA33 dose levels (0.25, 1.0, 5.0, and 10 mg/m2). Adverse events, pharmacokinetics, biodistribution, tumor biopsies, and immune responses to huA33 were evaluated. RESULTS: There were 12 patients entered into the trial (6 males and 6 females; age range, 39-66 years). No dose-limiting toxicity was observed. The biodistribution of huA33 showed excellent uptake of [131I]huA33 in metastatic colorectal carcinoma. Pharmacokinetic analysis showed no significant difference in terminal half-life (T1/2beta) between dose levels (mean +/- SD, 86.92 +/- 22.12 hours). Modeling of colon uptake of huA33 showed a T1/2 of elimination of 32.4 +/- 8.1 hours. Quantitative tumor uptake ranged from 2.1 x 10(-3) to 11.1 x 10(-3) %ID/g, and tumor/normal tissue and tumor/serum ratios reached as high as 16.3:1 and 4.5:1, respectively. Biosensor analysis detected low-level human anti-human antibody responses in four patients following huA33 infusion. CONCLUSIONS: huA33 shows selective and rapid localization to colorectal carcinoma in vivo and penetrates to the center of large necrotic tumors, and colon elimination half-life of huA33 is equivalent to basal colonocyte turnover. The excellent targeting characteristics of this humanized antibody indicate potential for the targeted therapy of metastatic colorectal cancer in future trials.

Adult↗

Urinary iodine concentration: United States National Health And Nutrition Examination Survey 2001-2002.

Urine iodine has been measured in the U.S. population by the National Health and Nutrition Examination Survey (NHANES) since 1971. A downward trend was noted between NHANES I (320 +/- 6 microg/L in 1971-1974) and NHANES III (145 +/- 3 microg/L in 1988-1994). This report presents data from NHANES 2001-2002 that indicates that the U.S. median urine iodine (UI) level has stabilized since the initial drop between NHANES I and NHANES III. The median UI concentration in the U.S. population in NHANES 2001-2002 was found to be 167.8 microg/L (95% confidence interval [CI] 159.3-177.6). The NHANES 2001-2002 data confirm the current stability of the U.S. iodine intake and continued adequate iodine nutrition for the country.

Adolescent↗

Flucloxacillin-induced aplastic anaemia and liver failure.

Flucloxacillin is a commonly prescribed semisynthetic penicillinase-resistant penicillin primarily used for the treatment of cutaneous staphylococcal infections. It is well-recognized that flucloxacillin may occasionally result in fatal hepatic injury. We report the case of a 40-year-old woman who developed fulminant hepatic failure and aplastic anaemia following a course of oral flucloxacillin. At the time of transplantation the patient was severely neutropenic. Post-transplant, the patient received single donor leucocyte transfusions, which resulted in a dramatic increase in neutrophil count. The patient was discharged from hospital after 120 days with normal liver function and recovered bone marrow. In this report, we discuss the care of patients with aplastic anaemia in the peritransplant setting.

Adult↗

Long-term reliability of endoscopic third ventriculostomy.

OBJECTIVE: To describe the short-term operative success and the long-term reliability of endoscopic third ventriculostomy (ETV) for treatment of hydrocephalus and to examine the influence of diagnosis, age, and previous shunt history on these outcomes. METHODS: We retrospectively analyzed 203 consecutive patients from a single institution who had ETV as long as 22.6 years earlier. Patients with hydrocephalus from aqueduct stenosis, myelomeningocele, tumors, arachnoid cysts, previous infection, or hemorrhage were included. RESULTS: The overall probability of successfully performing an ETV was 89% (84-93%). There was support for an association between the surgical success and the individual operating surgeon (odds ratios for success, 0.44-1.47 relative to the mean of 1.0, P = 0.08). We observed infections in 4.9%, transient major complications in 7.2%, and major and permanent complications in 1.1% of 203 procedures. Age was strongly associated with long-term reliability. The longest observed reliability for the 13 patients 0 to 1 month old was 3.5 years. The statistical model predicted the following reliability at 1 year after insertion: at 0 to 1 month of age, 31% (14-53%); at 1 to 6 months of age, 50% (32-68%); at 6 to 24 months of age, 71% (55-85%); and more than 24 months of age, 84% (79-89%). There was no support for an association between reliability and the diagnostic group (n = 181, P = 0.168) or a previous shunt. Sixteen patients had ETV repeated, but only 9 were repeated after at least 6 months. Of these, 4 procedures failed within a few weeks, and 2 patients were available for long-term follow-up. CONCLUSION: Age was the only factor statistically associated with the long-term reliability of ETV. Patients less than 6 months old had poor reliability.

Adolescent↗

Successful stenting for Budd-Chiari syndrome after pediatric liver transplantation: a case series and review of the literature.

Hepatic venous outflow obstruction, known as Budd-Chiari syndrome, is a rare but serious complication of orthotopic liver transplantation and may lead to graft loss. Our aim was to describe a single center experience of percutaneous interventional management of hepatic outflow obstruction post liver transplantation in children. Three children with post-transplant hepatic venous outflow obstruction were treated successfully with percutaneous stent placement. This resulted in long-term resolution of symptoms and was superior to balloon angioplasty both in our series and in cases reported in the literature. Stenting may be the treatment of choice for hepatic venous obstruction after pediatric liver transplantation, particularly if there is a recurrence of stenosis after balloon dilatation.

Budd-Chiari Syndrome↗

Frictional forces between cohesive powder particles studied by AFM.

A range of commercially important powders (hydrated alumina, limestone, titania and zeolite) and glass ballotini were attached to atomic force microscope cantilevers, and inter-particle friction forces studied in air using lateral force microscopy (LFM). The in situ calibration procedure for friction forces is described. LF images, line profiles, LF histograms, surface roughness, pull-off forces, and the load dependence of friction in the range 0-25 nN were studied for both particle-particle and particle-wall (steel) contacts. The single-particle friction results are discussed in terms of contact mechanics theory. Particle-particle contacts showed load-dependent friction, involving single asperity contacts (non-linear behaviour) or multi-asperity contacts (linear behaviour). Particle-wall contacts usually showed little load dependence and were more adhesive. The results are also related to shear stress-normal stress data (yield loci) for the same materials from bulk shear testers.

Friction↗

Adenomatoid tumor of the testes.

Adenomatoid tumors are rare benign neoplasms thought to be of mesothelial origin. Although most reported cases arise from the epididymis, rare cases have been reported in the spermatic cord, testicular tunica, ejaculatory ducts, prostate, and suprarenal recess. In female subjects, adenomatoid tumors are commonly found in the uterus and fallopian tubes. Because of the benign nature of this tumor, the treatment of choice is local excision. We describe a rare case of adenomatoid tumor of the testis treated by local excision.

Adenomatoid Tumor↗

Depression as a risk factor for mortality after coronary artery bypass surgery.

BACKGROUND: Studies that have shown clinical depression to be a risk factor for cardiac events after coronary artery bypass graft (CABG) surgery have had small sample sizes, short follow-up, and have not had adequate power to assess mortality. We sought to assess whether depression is associated with an increased risk of mortality. METHODS: We assessed 817 patients undergoing CABG at Duke University Medical Center between May, 1989, and May, 2001. Patients completed the Center for Epidemiological Studies-Depression (CES-D) scale before surgery, 6 months after CABG, and were followed-up for up to 12 years. FINDINGS: In 817 patients there were 122 deaths (15%) in a mean follow-up of 5.2 years. 310 patients (38%) met the criterion for depression (CES-D > or =16): 213 (26%) for mild depression (CES-D 16-26) and 97 (12%) for moderate to severe depression (CES-D > or =27). Survival analyses, controlling for age, sex, number of grafts, diabetes, smoking, left ventricular ejection fraction, and previous myocardial infarction, showed that patients with moderate to severe depression at baseline (adjusted hazard ratio [HR] 2.4, [95% CI 1.4-4.0]; p=0.001) and mild or moderate to severe depression that persisted from baseline to 6 months (adjusted HR 2.2, [1.2-4.2]; p=0.015) had higher rates of death than did those with no depression. INTERPRETATION: Despite advances in surgical and medical management of patients after CABG, depression is an important independent predictor of death after CABG and should be carefully monitored and treated if necessary.

Cause of Death↗

Carboplatin hypersensitivity reactions: re-treatment with cisplatin desensitisation.

OBJECTIVE: This aim of this study was to investigate the feasibility of re-treating patients who had experienced a hypersensitivity reaction to carboplatin with cisplatin following desensitisation. METHODS: Five patients with recurrent ovarian cancer who had a previous documented hypersensitivity reaction to carboplatin and a good clinical indication for continuing treatment with platinum were retreated following cisplatin desensitisation. All patients were rechallenged with cisplatin following a prolonged desensitisation protocol and the initial four patients then received subsequent cycles with a shortened protocol in an attempt to simplify and shorten the procedure. RESULTS: All five patients tolerated their first cycle of cisplatin on rechallenge using the full desensitisation protocol with no adverse reactions. Two patients received further treatments (one and three cycles) with a shortened protocol but treatment was terminated due to further adverse hypersensitivity reactions. Two patients received one further cycle with a shortened protocol and did not experience problems with hypersensitivity but treatment was stopped due to evidence of disease progression One patient received a further two cycles using the full desensitisation protocol without problems but treatment was stopped due to evidence of disease progression. CONCLUSIONS: A full cisplatin desensitisation protocol appears to be an effective way to re-treat patients who have previously experienced a hypersensitivity reaction to carboplatin. Attempts to shorten the procedure were associated with further allergic reactions, suggesting that the full protocol should be followed with each treatment.

Antineoplastic Agents↗

Physical activity, physiological, and psychomotor performance: a study of variously active older adult men.

This research examined varying levels of physical activity and psychomotor and physiological function in variously active older men. Very active moderately active, and low active participants were tested on simple (SRT) and choice reaction time (CRT), coincidence-anticipation timing (CAT), and VO2max. No significant differences for age or height were found, although percentage of fat, and weight were statistically different. Active groups were leaner and lighter. VO2max was significantly different between groups, as physically active groups yielded geater values. SRT and CAT also yielded significantly different results with more active participants showing better performance. No between-groups significant differences resulted for CRT. Generally, increased levels of physical activity were related to superior physiological outcomes and improved psychomotor peformance.

Aged↗

Biomonitoring of chemical exposure among New York City firefighters responding to the World Trade Center fire and collapse.

The collapse of the World Trade Center (WTC) on 11 September 2001 exposed New York City firefighters to smoke and dust of unprecedented magnitude and duration. The chemicals and the concentrations produced from any fire are difficult to predict, but estimates of internal dose exposures can be assessed by the biological monitoring of blood and urine. We analyzed blood and urine specimens obtained from 321 firefighters responding to the WTC fires and collapse for 110 potentially fire-related chemicals. Controls consisted of 47 firefighters not present at the WTC. Sampling occurred 3 weeks after 11 September, while fires were still burning. When reference or background ranges were available, most chemical concentrations were found to be generally low and not outside these ranges. Compared with controls, the exposed firefighters showed significant differences in adjusted geometric means for six of the chemicals and significantly greater detection rates for an additional three. Arrival time was a significant predictor variable for four chemicals. Special Operations Command firefighters (n = 95), compared with other responding WTC firefighters (n = 226), had differences in concentrations or detection rate for 14 of the chemicals. Values for the Special Operations Command firefighters were also significantly different from the control group values for these same chemicals and for two additional chemicals. Generally, the chemical concentrations in the other firefighter group were not different from those of controls. Biomonitoring was used to characterize firefighter exposure at the WTC disaster. Although some of the chemicals analyzed showed statistically significant differences, these differences were generally small.

Air Pollutants, Occupational↗