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Biomedical subjects

T Wright

Publications and source records attributed to T Wright.

At least 19 recordsLinked to original sources
PubMed2007

Quantitative analysis of HBV cccDNA from clinical specimens: correlation with clinical and virological response during antiviral therapy.

Attempts to investigate changes in various forms of intrahepatic hepatitis B virus (HBV) DNA during antiviral therapy have been hampered by limitations in technologies and scarcity of adequate tissue for analysis. We used a sensitive, specific assay to detect and quantitate covalently closed circular DNA (cccDNA) from total intrahepatic HBV DNA in clinical liver specimens. Total HBV DNA and cccDNA from 21 needle-biopsy specimens were quantified, with levels ranging from 0.1 to 9.8 copies/cell and 0.3 to 491.0 copies/cell, respectively. Then, we performed the same determinations on baseline and week-52 liver needle-biopsy specimens from eight patients enrolled in a clinical trial and evaluated the association between intrahepatic HBV DNA levels and serological and virological endpoints. In most patients, levels of intrahepatic HBV DNA, including cccDNA, decreased over the 52-week study, regardless of therapy or serological outcome. Higher ratios of cccDNA to total HBV DNA were detected at week 52 than at baseline indicating a shift in predominance of nonreplicating virus in posttreatment specimens. In patients who achieved treatment-related or spontaneous hepatitis B e antigen (HBeAg) responses, including those harbouring tyrosine-methionine-aspartate-aspartate-mutant HBV, levels of intrahepatic and serum HBV DNA suppression were greater than those in patients without HBeAg responses. In conclusion, this pilot study of intrahepatic HBV replicative forms in patients with chronic hepatitis B indicated that total intrahepatic and, specifically, cccDNA levels are not static but change as a reflection of serological and virological events.

Alanine Transaminase↗
PubMed2006

Glenoid loosening in response to dynamic multi-axis eccentric loading: a comparison between keeled and pegged designs with an equivalent radial mismatch.

Glenoid loosening is a common failure mode observed in total shoulder arthroplasty. In an effort to isolate the affect of differing fixation techniques on loosening, an edge displacement test was conducted using two, pear-shaped, UHMWPE glenoid designs: one keel and one peg, each having a glenohumeral radial mismatch of 4.3 mm. The susceptibility of each design to loosening was established by quantifiably comparing the maximum glenoid edge displacement before and after 100,000 cycles of eccentric loading by the humeral head along both the superoinferior (SI) and anteroposterior (AP) glenoid axes. Regardless of the axes tested, the results of this study indicate that no discernable difference in edge displacement (distraction and compression) occurred before or after cyclic, eccentric loading for either the keeled or pegged glenoid designs. Additionally, each keel andpeg glenoid remained firmly fixed after testing, suggesting that either fixation technique provides sufficient resistance to edge displacement.

Arthroplasty, Replacement↗
PubMed2006

Anatomic validation of an "anatomic" shoulder system.

An anatomic study was conducted on 49 dried cadaveric humeri and 24 dried cadaveric scapula to ascertain the variability of the following parameters: humeral neck angle, humeral head retroversion, humeral head medial offset, humeral head posterior offset, humeral head diameter glenoid height, glenoid width, and the glenoid height to width ratio. For verification purposes, the results of this study were found to be within 1.5% to 14.3% of other anatomic studies published in the literature. This observed variability was then compared to that provided by an "anatomic" shoulder prosthesis (Equinoxe, Exactech, Inc.); viewed independently, this prosthesis can restore humeral neck angle in 94% of humeri, "secondary" retroversion in 92% of humeri, medial offset in 100% of humeri, posterior offset in 100% of humeri, and humeral head diameter in 96% of humeri. Additionally, the glenoid prosthesis height to width ratio was found to be within 5% and 10% of 71% and 96% of cadaveric glenoids, respectively. The results of this analysis indicate that a dual-offset "anatomic " shoulder prosthesis has the capability to successfully restore glenohumeral anatomy in this representative population.

Arthroplasty↗
PubMed2004

DairyBeef: maximizing quality and profits--a consistent food safety message.

To respond to meat safety and quality issues in dairy market cattle, a collaborative project team for 7 western states was established to develop educational resources providing a consistent meat safety and quality message to dairy producers, farm advisors, and veterinarians. The team produced an educational website and CD-ROM course that included videos, narrated slide sets, and on-farm tools. The objectives of this course were: 1) to help producers and their advisors understand market cattle food safety and quality issues, 2) help maintain markets for these cows, and 3) help producers identify ways to improve the quality of dairy cattle going to slaughter. DairyBeef. Maximizing Quality & Profits consists of 6 sections, including 4 core segments. Successful completion of quizzes following each core segment is required for participants to receive a certificate of completion. A formative evaluation of the program revealed the necessity for minor content and technological changes with the web-based course. All evaluators considered the materials relevant to dairy producers. After editing, course availability was enabled in February, 2003. Between February and May, 2003, 21 individuals received certificates of completion.

Animals↗
PubMed2003

Seroprevalence of human papillomavirus-16, -18, -31, and -45 in a population-based cohort of 10000 women in Costa Rica.

Human papillomavirus (HPV) seroprevalence and determinants of seropositivity were assessed in a 10049-woman population-based cohort in Guanacaste, Costa Rica. Serologic responses based on VLP-based ELISA were obtained from the plasma collected at study enrollment in 1993/1994 for HPV-16 (n=9949), HPV-18 (n=9928), HPV-31 (n=9932), and HPV-45 (n=3019). Seropositivity was defined as five standard deviations above the mean optical density obtained for studied virgins (n=573). HPV-16, -18, -31, and -45 seroprevalence was 15, 15, 16, and 11%, respectively. Of women DNA-positive for HPV-16, -18, -31, or -45, seropositivity was 45, 34, 51, and 28%, respectively. Peak HPV seroprevalence occurred a decade after DNA prevalence; lifetime number of sexual partners was the key determinant of seropositivity independent of DNA status and age. DNA- and sero-positive women showed the highest risk for concurrent CIN3/cancer, followed by DNA-positive, sero-negative women.

Adolescent↗
PubMed2003

The safety and tolerability of daily infergen plus ribavirin in the treatment of naíïve chronic hepatitis C patients.

The treatment of chronic hepatitis C patients was enhanced when the combination of interferon alfa-2b and ribavirin was shown to be safe and more effective than interferon monotherapy. To date, no published reports have addressed the use of consensus interferon (CIFN) when combined with ribavirin. We conducted a pilot study to compare the safety and tolerability of daily CIFN plus ribavirin to CIFN monotherapy for the initial treatment of chronic hepatitis C patients. Forty subjects were randomized to two treatment groups; CIFN 9 microg daily, or CIFN 9 microg daily plus ribavirin 1000 or 1200 mg daily. All subjects received 48 weeks of therapy except for nongenotype 1 subjects in the combination treatment group who received only 24 weeks of therapy. The results show that at baseline, age, gender, risk factors, race, RNA titres, and liver histology were not different between the two groups. The proportion of subjects with genotype 1 infection was 50% (10/20) and 55% (11/20) for the monotherapy and combination therapy groups, respectively. Fifty (10/20) and sixty-five (13/20) per cent of subjects in the monotherapy and combination therapy groups exhibited a 2-log or greater decrease in viral titre at week 12 (P = NS). Using intent-to-treat analysis, 20% and 40% of enrolled subjects exhibited a sustained viral response in the monotherapy and combination therapy groups, respectively (P = NS). The proportion of subjects requiring dose reduction was 55% (11/20) and 65% (13/20), respectively. Study discontinuations for any reason were 25% (5/20) and 35% (7/20) for the monotherapy and combination groups, respectively. Discontinuations due to adverse events related to study drug were 20% (4/20) and 25% (5/20), respectively. A total of four serious adverse events occurred, two in each treatment group, only one of which was determined to be study-drug related. It is concluded that the safety and tolerability profiles of the two treatments were similar suggesting that daily dosing of CIFN may be difficult to tolerate resulting in discontinuation of therapy in a significant proportion of patients. The combination regimen resulted in a trend towards a higher viral response rate than monotherapy treatment. These data suggest that CIFN may be safely combined with ribavirin and may enhance the sustained response rate but is not well tolerated in US patients when given in a daily dosing regimen.

Drug Therapy, Combination↗
PubMed2002

The trematodes of groupers (Serranidae: Epinephelinae): knowledge, nature and evolution.

Groupers (Epinephelinae) are prominent marine fishes distributed in the warmer waters of the world. Review of the literature suggests that trematodes are known from only 62 of the 159 species and only 9 of 15 genera; nearly 90% of host-parasite combinations have been reported only once or twice. All 20 families and all but 7 of 76 genera of trematodes found in epinephelines also occur in non-epinephelines. Only 12 genera of trematodes are reported from both the Atlantic-Eastern Pacific and the Indo-West Pacific. Few (perhaps no) species are credibly cosmopolitan but some have wide distributions across the Indo-West Pacific. The hierarchical 'relatedness' of epinephelines as suggested by how they share trematode taxa (families, genera, species) shows little congruence with what is known of their phylogeny. The major determinant of relatedness appears to be geographical proximity. Together these attributes suggest that host-parasite co-evolution has contributed little to the evolution of trematode communities of epinephelines. Instead, they appear to have arisen through localized episodes of host-switching, presumably both into and out of the epinephelines. The Epinephelinae may well be typical of most groups of marine fishes both in the extent to which their trematode parasites are known and in that, apparently, co-evolution has contributed little to the evolution of their communities of trematodes.

Adaptation, Physiological↗
PubMed2001

Quantitative analysis of hepatitis C virus in peripheral blood and liver: replication detected only in liver.

Prior studies seeking evidence of viral replication in peripheral lymphocytes of hepatitis C virus (HCV)-infected patients have yielded conflicting results. This study sought to quantitatively determine whether a permissive HCV cell interaction could be detected in leukocytes from infected patients. Peripheral leukocytes from chronically infected patients were purified and were tested for HCV RNA. The results show that virus load is highest in B cells. Other subsets of peripheral leukocytes consistently had very low levels of viral RNA or were negative. Negative-strand HCV was found only in hepatocytes. To determine whether HCV replication could be induced by activation, B cells from HCV-infected patients were stimulated in vitro. No HCV replicating in peripheral leukocytes was detected by a highly sensitive assay. If HCV replication occurs in the leukocyte subsets analyzed here, it is at extremely low levels or occurs under alternate physiological conditions.

Adult↗
PubMed2001

Relationship of Campylobacter toxigenicity in vitro to the development of postinfectious irritable bowel syndrome.

Campylobacter enteritis is associated with a significant risk of developing irritable bowel syndrome, but the mechanism is unknown. This study ascertained bowel symptoms in 93 patients 3 months after Campylobacter jejuni enteritis infection. The infecting organisms were cultured, and the effects of culture supernatants on toxin-sensitive epithelial cell monolayers (HEp-2, Green monkey kidney epithelial [Vero], and CHO-K1) were investigated. In all, 50, 43, and 41 of the isolates showed toxigenic effects on HEp-2, CHO-K1, and Vero cells, respectively. Persistently changed bowel habit was reported by 9 of 50 persons with HEp-2 toxin-positive infections but by only 2 of 43 with isolates negative for toxin (chi2=4.0; P<.05). Toxicity to HEp-2 and Vero cells was associated with significantly increased numbers of days with loose stools 6 months after C. jejuni enteritis infection (both, P<.05). Thus, long-term symptoms that occur Campylobacter infection are significantly associated with bacterial toxicity.

Adolescent↗
PubMed2001

Shoulder MRI refinements: differentiation of rotator cuff tear from artifacts and tendonosis, and reassessment of normal findings.

One of the difficulties with rotator cuff imaging lies in the normal variability of the tendon's signal. There may be intermediate signal present within the tendon because of magic-angle phenomenon, muscle and tendon fiber interdigitation, or tendinopathy related to degenerative changes or overuse injury. Partial and complete rotator cuff tears should be distinguishable from these causes of intermediate signal if water signal is reliably identified. This article reviews the important issue of distinguishing between rotator cuff tear and other causes of high signal in the rotator cuff, including artifacts and tendonosis. We include a review of the literature and a brief report of a study we conducted on 20 shoulders of 14 asymptomatic, young volunteers. In this study, the rotator cuff tendons were evaluated for abnormal signal at different TE values to determine at what TE the interpreters were able to confidently distinguish the high-signal intensity of a tear (water) from the intermediate signal intensity associated with artifact and tendinopathy. Readers were able to distinguish water and tendon signal in 70% to 100% of fast-spin echo (FSE) fat-saturated images with TE of 66, but there was interobserver variability at this TE, suggesting that it is less reliable than 88 ms in the identification of rotator cuff tears. By using FSE fat-saturated sequences with TE of 88 and fast spin echo inversion recovery (FSEIR) sequences, readers at all levels of experience were able to differentiate water signal intensity from tendon signal intensity in 100% of cases. Therefore, we suggest that either FSEIR images or FSE fat-saturated images with TE greater than 66 be used to facilitate the differentiation of fluid signal from intermediate increased signal intensity in rotator cuff imaging. Additionally, this article reviews the normal findings of shoulder magnetic resonance imaging (MRI) as revealed by the asymptomatic subjects included in our study, and assesses these findings in respect to previous publications. The normal features reviewed include the subacromion-subdeltoid (SA/SD) bursa, the biceps tendon sheath, the acromioclavicular (AC) joint, and the greater tuberosity of the humerus. A small amount of fluid was commonly seen in the SA/SD bursa, as well as the biceps tendon sheath. Subjective down-sloping of the acromion in the coronal plane, mild degenerative change of the AC joint, and undersurface spurring of the AC joint were uncommon in our normal subjects. Cystic change limited to the posterior aspect of the greater tuberosity was identified in 15% to 45% of shoulders.

Artifacts↗
PubMed2001

Stability of the lumbar spine after intradiscal electrothermal therapy.

OBJECTIVE: To assess the stability of the human lumbar cadaveric spinal motion segment before and after treatment with intradiscal electrothermal therapy (IDET). DESIGN: An in vitro biomechanic analysis of 5 human cadaveric spinal motion segments by using nondestructive biomechanic testing in flexion/extension, lateral bending, and axial rotation with loads of 0N, 600N, and 1200N. SETTING: University-based hospital research center. CADAVERS: Spinal unit specimens (upper and middle lumbar) from 5 human cadavers (age range, 39-79yr). INTERVENTIONS: A spinal catheter consisting of a thermal-resistive heating coil was placed circumferentially into the outer annulus by using the standard extrapedicular discographic technique through a 17-gauge introducer needle. The disc was then heated in a saline bath (37 degrees C) from 65 degrees C up to 90 degrees C for a total of 17 minutes. MAIN OUTCOME MEASURE: The stability of the spinal segments was measured before and shortly after IDET. Stability of the spine was measured as the compliance of the spine (the angular deformation afforded by the spine under applied bending moments). RESULTS: With increasing preloads, there is a decrease in motion of the spinal segment in all planes of testing. However, there was no significant difference (p >.05) in the stability of the lumbar spine before and after treatment with IDET. CONCLUSIONS: IDET does not destabilize the spinal motion segment in vitro.

Adult↗
PubMed2001

A multicenter United States-Canadian trial to assess lamivudine monotherapy before and after liver transplantation for chronic hepatitis B.

Seventy-seven liver transplant candidates were enrolled in a multicenter study in which patients were treated with lamivudine (100 mg daily) without the adjunctive use of hepatitis B immune globulin. Treatment was begun while patients awaited liver transplantation and continued after transplantation. All were hepatitis B surface antigen (HBsAg) positive, and 61% had detectable hepatitis B e antigen (HBeAg) and HBV DNA when treatment was begun. Forty-seven underwent liver transplantation and 30 did not. Median study participation was 38 months (range, 2.7-48.5) in the transplanted patients and 26 months (range, 0.1-37) in the nontransplanted group. Twenty-five of 42 (60%) transplanted patients with 12 or more weeks of posttransplantation follow-up were HBsAg negative at the last study visit. At treatment week 156, 13 of 22 (59%) remained HBsAg negative, and all 9 reinfected patients were HBV-DNA positive before treatment. In the nontransplanted patients, HBeAg was initially detectable in 20 of 27 (74%) but this decreased to 3 of 17 (18%) after 104 weeks of treatment, and significant improvement in biochemical parameters was observed. HBV-DNA polymerase mutants were detected in 15 (21%) and 6 (20%) of the transplanted and nontransplanted patients, respectively. When compared with historical cohorts, lamivudine-treated patients appeared to have improved survival, and transplanted patients had a decrease in the rate of recurrent HBV infection. Lamivudine therapy was partially effective in preventing recurrent HBV infection when given before and after transplantation. Thus, future trials using a combination of HBIg and lamivudine are needed to assess the optimal prophylactic therapy.

Adult↗
PubMed2001

A multicenter study of lamivudine treatment in 33 patients with hepatitis B after liver transplantation.

Hepatitis B virus (HBV) infection after liver transplantation (LT) may lead to severe and rapidly progressive graft failure. Antiviral treatment may be of benefit in selected patients with recurrent hepatitis B post-LT. The aim of this prospective open-label study is to determine the safety and efficacy of lamivudine in 33 liver transplant recipients with active HBV infection. The median time from LT to study enrollment was 51 months, all patients were hepatitis B surface antigen positive, and 75% and 94% of subjects had detectable hepatitis B e antigen (HBeAg) and HBV DNA at entry, respectively. The median duration of lamivudine treatment on study was 85 weeks, during which time median HBV DNA levels became undetectable by 16 weeks and 9% of patients lost previously detectable HBeAg. Serum alanine aminotransferase (ALT) levels improved in most patients and normalized in 27% of patients with elevated values pretreatment. Serum bilirubin and albumin levels significantly improved in patients with abnormal values at entry (P <.05). Virological breakthrough was detected in 13 subjects after a median of 61 weeks of lamivudine treatment and was confirmed to be caused by YMDD mutants in all patients tested. None of the patients with virological breakthrough showed a complete loss of clinical response to lamivudine. Serum ALT and bilirubin levels in patients with and without virological breakthrough were not significantly different at last study follow-up. Study results show that lamivudine is safe and effective in liver transplant recipients with recurrent hepatitis B. However, the high rate of virological breakthrough with prolonged therapy indicates the need for further studies of combination antiviral therapy in this patient population. Our results and others further establish the improving long-term outcomes with LT for patients with hepatitis B through advances in prevention of reinfection, as well as the availability of safe and effective antiviral therapies to treat patients with HBV recurrence.

Adult↗
PubMed2001

Plasma tissue factor pathway inhibitor levels as a marker for postoperative bleeding after enoxaparin use in deep vein thrombosis prophylaxis in orthopedics and general surgery.

Low-molecular-weight heparins (LMWH) are widely used as antithrombotic prophylactic pharmaceutical agents in orthopedic and general surgery. Their antithrombotic characteristics are expressed by plasma mediators such as anti-Xa. anti-IIa, and increased release of tissue factor pathway inhibitor (TFPI) from vascular endothelium. The purpose of this clinical research is to study the relation between plasma levels of these mediators and postoperative bleeding. Forty-one consecutive patients undergoing hip or knee arthroplasty (n = 36) and colectomy (n = 5) received the standard enoxaparin (a LMWH) dose preoperatively (general surgery) or immediately postoperatively (orthopedic surgery). Major bleeding was defined as a postoperative drop of > or = 5 g/dL) of hemoglobin. The authors observed that there was a linear relationship between an increase in free/total TFPI ratio levels and postoperative bleeding. When that ratio increased by >60%, the hemoglobin dropped to >5 g/dL (n = 13). This relationship between free/total TFPI ratio increase and postoperative bleeding was statistically significant (P < 0.001). Those who did not bleed (hemoglobin drop was less than 5 g/dL) (n = 28) had a ratio increase (if any) of less than 50%. However, the authors did not observe any statistical relationship between anti-Xa, anti-IIa, or prothrombin time and postoperative bleeding in patients receiving LMWH for deep vein thrombosis prophylaxis in orthopedic and general surgery patients. The authors recommend a pre- and postoperative ratio level measurement whenever major bleeding is anticipated, as adjustments of LMWH dose or frequency might be necessary.

Anticoagulants↗
PubMed2000

The effects of chronic, sustained-release moxonidine therapy on clinical and neurohumoral status in patients with heart failure.

AIMS: Congestive heart failure (CHF) is characterized by elevated plasma norepinephrine (PNE) associated with a poor prognosis. Moxonidine selectively stimulates medullary imidazoline receptors which centrally inhibit sympathetic outflow and potently suppress levels of circulating PNE. This study was designed to evaluate the effects of central sympathetic inhibition on clinical and neurohumoral status in patients with CHF. METHODS AND RESULTS: This study evaluated 25 patients (age=69+/-7 years, 20 males) with symptomatic CHF (NYHA II-III), stabilized on standard therapy. The mean ejection fraction was 28+/-7% at baseline. Patients were titrated in a double-blind fashion to 11 weeks of oral therapy with placebo (n=9) or sustained-release (SR) moxonidine 0.9 mg bid (n=16). Clinical and neurohumoral status were evaluated at baseline, on chronic therapy at the target dose, and during cessation of therapy. All patients completed the trial and reached the target dose. Dry mouth, symptomatic hypotension, and asthenia were more frequent in the moxonidine SR-treated group. PNE was substantially reduced after 6 weeks at the maximum dose (0.9 mg bid) by 50% vs. placebo (P<0. 0005). A reduction in 24-h mean heart rate (P<0.01) was correlated to the reduction in PNE (r=0.70, P<0.05). A 36% increase in the standard deviation of normal-to-normal intervals (SDNN) was observed in the moxonidine SR group vs. a 2% decrease for placebo (P=0.06); for the root mean square of successive differences (rMSSD), there was a 21% increase for moxonidine SR vs. a 19% decrease for placebo (P<0.05). Abrupt cessation of chronic therapy resulted in substantial increases in PNE, blood pressure, and heart rate. CONCLUSIONS: Chronic therapy with a sustained-release formulation of moxonidine in patients with CHF was well tolerated, with substantial and sustained reductions in PNE. The tachyarrhythmias were attenuated, with evidence of improved autonomic tone. Due to the observed effects following moxonidine discontinuation, tapering of therapy is recommended.

Blood Pressure↗
PubMed2000

Oral contraceptive and benign ovarian tumors.

Whether use of combined oral contraceptives (OC) protects against benign ovarian tumors is unknown. A case-control study of pathologically confirmed benign ovarian tumors was conducted in the New York City area and included cases diagnosed from January 1, 1992, to December 31, 1993, and controls identified by random digit dialing. There were 196 cases with serous adenomas, 176 with teratomas, 311 with endometriomas, and 65 with mucinous adenomas. Interview data were used to determine contraceptive use. Ever use of OC was associated with a decreased risk of these benign tumors (age- and hospital-adjusted odds ratio = 0.79, 95% confidence interval: 0.60, 1.05). In histologic subgroup analyses, the risk of ovarian tumors was reduced for both current and past OC users. Among tumor subtypes, the risk reduction was greatest for women who had endometriotic lesions. The risk reduction also was greater for women who had used OC for more than 24 months. Protection against benign ovarian tumors may be an additional noncontraceptive benefit of OC use.

Adenoma↗