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Biomedical subjects

J W Jones

Publications and source records attributed to J W Jones.

At least 73 records · Page 4Linked to original sources
PubMed2000

Successful hand transplantation. One-year follow-up. Louisville Hand Transplant Team.

BACKGROUND: On the basis of positive results in studies of the transplantation of pig extremities and the information exchanged at an international symposium on composite tissue transplantation, we developed a protocol for human hand transplantation. METHODS: After a comprehensive pretransplantation evaluation and informed-consent process, the left hand of a 58-year-old cadaveric donor, matched for size, sex, and skin tone, was transplanted to a 37-year-old man who had lost his dominant left hand 13 years earlier. Immunosuppression consisted of basiliximab for induction therapy and tacrolimus, mycophenolate mofetil, and prednisone for maintenance therapy. RESULTS: The cold-ischemia time of the donor hand was 310 minutes. There were no intraoperative or early postoperative complications. Moderate acute cellular rejection of the skin of the graft developed 6, 20, and 27 weeks after transplantation. All three episodes resolved completely after treatment with intravenous methylprednisolone and topical tacrolimus and clobetasol. Temperature, pain, and pressure sensation had developed in the hand and fingers by one year. At one year, the patient had regained the ability to perform many functional activities with his left hand that he had not been able to perform with his prosthesis, such as throwing a baseball, turning the pages of a newspaper, writing, and tying his shoelaces. CONCLUSIONS: Early success has been achieved in hand transplantation with the use of currently available immunosuppressive drugs.

Adult↗
PubMed2000

The healthcare professional and the Bolam test.

This article will cover the history of the tort of negligence and how the judgement in the case of Donoghue v Stevenson enabled the courts to 'develop the law' to allow the concept of a 'duty of care' to develop which was extended to include healthcare professionals. The Bolam test is then described and how it has come to play such a prominent role in assisting the courts to assess if an appropriate standard has been achieved in medical negligence litigation. Attempts by the courts to move away from Bolam are discussed and the difficulties encountered because of the reluctance of the appellate courts to approve such decisions. Finally the recent House of Lords decision in Bolitho v City and Hackney Health Authority is examined and the implications this may have on the Bolam test.

Benchmarking↗
PubMed2000

Osteomyocutaneous flap as a preclinical composite tissue allograft: swine model.

Composite tissue allotransplantation (CTA) constitutes one of the last frontiers of microsurgery. Prior to its clinical application, the long-term efficacy of modern immunotherapy must be tested in a pre-clinical CTA model. Based on the concept of osteomyocutaneous forearm flap, we developed a CTA flap model in swine. After identifying the vascular territory of the flaps in six pigs (vascular casting), flaps were transplanted from mismatched donor to recipient pigs (n = 6). Rejection was assessed daily by visual inspection and histopathology of biopsy specimens. Recipient pigs were able to ambulate immediately following surgery. There were no flap failures owing to technical or surgical complications. Rejection occurred over a period of 7 days as manifested by edema, cellular infiltration, epidermalysis, and thrombosis. This pre-clinical flap model is excellent for evaluating the effectiveness of modern immunotherapy because it is anatomically and immunologically relevant and because the minimal morbidity caused to the animal permits long-term studies.

Animals↗
PubMed2000

Immunosuppressive agents in transplantation: mechanisms of action and current anti-rejection strategies.

Over the past century, the concept of interfering with the immune response at various sites by blocking the formation, stimulation, proliferation, and differentiation of lymphocytes has led to relentless development of new immunosuppressive drugs. These agents are associated with reduced risk of short- and long-term toxicity and have dramatically improved allograft and patient survival, especially in recipients of solid organ transplants. Current protocols in such patients are nearly all calcineurin-inhibitor based, using cyclosporine or tacrolimus, as part of dual, triple, or sequential therapy. This review focuses on agents currently in clinical use at transplant centers in United States. The drugs are described in terms of their basic mechanisms of action, therapeutic uses, clinical studies, and adverse effects. In addition, the efficacy and toxicity of a few promising new therapeutic approaches are examined. Finally, important challenges regarding pharmacological immunosuppression as it relates to solid organ and composite tissue allotransplantation are discussed.

Drug Therapy, Combination↗
PubMed2000

Vector competence of Peruvian mosquitoes (Diptera: Culicidae) for epizootic and enzootic strains of Venezuelan equine encephalomyelitis virus.

Mosquitoes collected in the Amazon Basin, near Iquitos, Peru, were evaluated for their susceptibility to epizootic (IAB and IC) and enzootic (ID and IE) strains of Venezuelan equine encephalomyelitis (VEE) virus. After feeding on hamsters with a viremia of approximately 10(8) plaque-forming units of virus per milliliter, Culex (Melanoconion) gnomatus Sallum, Huchings, & Ferreira, Culex (Melanoconion) vomerifer Komp, and Aedes fulvus (Wiedemann) were highly susceptible to infection with all four subtypes of VEE virus (infection rates > or = 87%). Likewise, Psorophora albigenu (Peryassu) and a combination of Mansonia indubitans Dyar & Shannon and Mansonia titillans (Walker) were moderately susceptible to all four strains of VEE virus (infection rates > or = 50%). Although Psorophora cingulata (Fabricius) and Coquillettidia venezuelensis (Theobald) were susceptible to infection with each of the VEE strains, these two species were not efficient transmitters of any of the VEE strains, even after intrathoracic inoculation, indicating the presence of a salivary gland barrier in these species. In contrast to the other species tested, both Culex (Melanoconion) pedroi Sirivanakarn & Belkin and Culex (Culex) coronator Dyar & Knab were nearly refractory to each of the strains of VEE virus tested. Although many of the mosquito species found in this region were competent laboratory vectors of VEE virus, additional studies on biting behavior, mosquito population densities, and vertebrate reservoir hosts of VEE virus are needed to incriminate the principal vector species.

Animals↗
PubMed2000

Lasers in the treatment of ischaemic heart disease.

Mounting evidence showing that transmyocardial laser revascularization (TMR) is a safe and effective treatment for angina pectoris arrives just as an increasing number of patients who have undergone angioplasty and coronary artery bypass grafting experience failure with time. TMR, nevertheless, remains controversial. It appears to relieve the symptoms without treating the underlying atherosclerotic disease, and its method of action is unproven. Like angioplasty and coronary bypass, TMR in fact offers palliation rather than a cure for atherosclerotic heart disease. The most sensible current formulations of the therapeutic mechanism of TMR posit a reconfiguration of the microcirculation, with blood shunted from epicardial to endocardial areas. These unresolved issues notwithstanding, TMR benefits patients with end-stage coronary disease and represents a pioneering effort to remodel the microcirculation of patients with arteriosclerotic occlusive disease.

Angina Pectoris↗
PubMed2000

Limited potential for transmission of live dengue virus vaccine candidates by Aedes aegypti and Aedes albopictus.

To evaluate the transmission risk of four live dengue (DEN) vaccine candidates developed by the U.S. Army (DEN-1, 45AZ5 PDK 20; DEN-2, S16803 PDK 50; DEN-3, CH53489 PDK 20; and DEN-4, 341750 PDK 20), we tested 3,010 Aedes aegypti and 1,576 Aedes albopictus mosquitoes blood-fed on 21 volunteers who had been administered one of the four vaccine candidates or the licensed yellow fever (YF) vaccine (17D). We used an indirect immunofluorescence assay (IFA) to detect DEN or YF viral antigen in the heads of mosquitoes. Corresponding to the lack of a detectable viremia among volunteers inoculated 8-13 days previously with live DEN-1 or DEN-2 vaccine candidates, only six mosquitoes developed disseminated infections after feeding on these volunteers. These six mosquitoes included 4 of 247 Ae. albopictus fed on volunteers inoculated with the DEN-1 vaccine candidate and 2 of 528 Ae. aegypti fed on volunteers inoculated with the DEN-2 vaccine candidate. Infection was confirmed in each of these IFA-positive mosquitoes by isolating infectious virus from the mosquito's body in Vero-cell culture. None of the 1,252 or the 969 mosquitoes fed on DEN-3 or DEN-4 recipients, respectively, were infected. Overall, dissemination rates in Ae. albopictus and Ae. aegypti were low. Dissemination rates were 0.5%, 0.3%, < 0.1%, and < 0.1% for the DEN-1 through DEN-4 vaccine candidates, respectively. Because of the observed low dissemination rates, it is unlikely that these vaccine viruses would be transmitted under natural conditions.

Aedes↗
PubMed2000

Bilateral internal thoracic artery operations in the elderly.

BACKGROUND: Elderly surgical patients have higher operative morbidity and mortality than younger cohorts, particularly when the procedure is lengthy and complex. While use of bilateral internal thoracic arteries (BITA) is often associated with increased surgical risk, we nevertheless hypothesized that the use of BITA in elderly coronary artery bypass patients would not significantly increase their operative risk beyond that encountered using single internal thoracic arterial (SITA) or saphenous vein grafts (SVG). We maintained that arterial grafts remain essentially unaffected by arteriosclerosis, and that extension of a high-quality life is a desirable outcome regardless of age at operation. METHODS EXPERIMENTAL DESIGN: We studied myocardial revascularization in 673 patients over 65 years of age at the time of operation. All operations were conducted or supervised by a single surgeon during a ten-year period from January 1986 to January 1996. Preoperative and operative dates were recorded prospectively. SETTING: All patients underwent coronary artery bypass grafting. INTERVENTIONS: The study compared outcomes in patients having all veins, SITA or BITA operations. For the first analysis, 673 patients were divided into three groups: 163 patients (Group 1) had saphenous vein used for all bypasses; 338 patients had a SITA with supplemental vein grafts (Group 2); and 172 patients (Group 3) had BITAs with additional vein grafts as needed. In the second analysis, Group 3 was subdivided and grouped by the coronary arteries which received the ITA grafts, and the analysis was repeated. One hundred and sixteen patients (Group 3A) underwent traditional placement of ITA bypasses (left ITA to the LAD, right ITA to the RCA); in Group 3B, 56 patients received revascularization of branches of the left coronary artery (left ITA to the circumflex system, right ITA to the LAD). MEASURES: We communicated directly with 90.5% of the patients, their families, or their physicians. The survival status of the remainder was determined through the National Social Security Death Index Network. This allowed us to obtain follow-up longevity data for 100% of the study sample at a mean observation period of 5.03+/-3.1 years with variation between 10.8 years to 2.4 years. RESULTS: A multivariate analysis showed that placement of both ITA grafts to left-sided arteries in older patients independently improved long-term survival (p=0.031). CONCLUSIONS: The BITA procedure does not have greater operative morbidity or mortality in the elderly despite the length or complexity of the surgery. To realize improved long-term survival rates, however, both ITAs must be grafted to the left coronary artery branches.

Aged↗
PubMed2000

Site directed mutagenesis of the human Rh D antigen: molecular basis of D epitopes.

Previous attempts to define the molecular configuration of D epitopes has been confined to the analysis of the serological profile and Rh D molecular structure of partial D phenotypes. There are numerous drawbacks in this approach, most fundamental of which is that with the exception of RoHar, partial D phenotypes are defined by the loss of D epitope expression, and is thus difficult to directly correlate a specific amino acid to a particular D epitope. Furthermore, most partial D phenotypes are associated with multiple amino acid changes in the mutant Rh protein species associated with partial D expression. In our study we have applied site directed mutagenesis to introduce RhD amino acids in a stepwise manner to a Rh cE cDNA. This cDNA was introduced into K562 cells using retroviral mediated gene delivery, and D epitope expression analysed by flow cytometry. Our study provides evidence for at least six different epitope clusters on the external face of the Rh D protein. The relative predicted positions of these epitope clusters has resulted in us presenting a model for the hypothetical arrangement of external Rh D protein loops.

Epitopes↗
PubMed2000

Epitopes on Rh proteins.

Analyses of the reactions of monoclonal anti-D with Rh D variant red cells have shown that there are at least 24 different epitopes of the Rh D antigen. Similar studies Of Rh E variant red cells with monoclonal anti-E indicate that there are at least 4 epitopes of the Rh E antigen. The relation of these serologically defined epitopes to the structure of the Rh proteins is reviewed. Most epitopes are discontinuous, with critical residues present in different loops of the proteins.

Antigens↗
PubMed1999

Molecular configuration of Rh D epitopes as defined by site-directed mutagenesis and expression of mutant Rh constructs in K562 erythroleukemia cells.

The Rh D antigen is the most clinically important protein blood group antigen of the erythrocyte. It is expressed as a collection of at least 37 different epitopes. The external domains of the Rh D protein involved in epitope presentation have been predicted based on the analysis of variant Rh D protein structures inferred from their cDNA sequences and their D epitope expression. This analysis can never be absolute because (1) most partial D phenotypes involve multiple amino acid changes in the Rh D protein and (2) deficiency for 1 or more epitopes may be due to gross structural alteration in the variant Rh D protein structure. We report here the amino acid requirements for the majority of D epitopes. They have been defined by generating a series of novel Rh mutant constructs by mutagenesis using an Rh cE cDNA as template and mutagenic oligonucleotide primers. When transfected into K562 cells, the D epitope expression of the derived mutant clones was then assessed by flow cytometry. The introduction of 9 externally predicted Rh D-specific amino acids on the Rh cE protein was sufficient to express 80% of all tested D epitopes, whereas other clones expressed none. We concluded from our data that the D epitope expression is consistent with at least 6 different epitope clusters localized on external regions of the Rh D protein, most involving overlapping regions within external loops 3, 4, and 6.

Epitopes↗
PubMed1999

A new cryptand: synthesis and complexation with paraquat.

[formula: see text] Inspired by folded, nonpseudorotaxane complexes of bis(m-phenylene)-32-crown-10 systems, we synthesized a new bicyclic crown ether containing two 1,3,5-phenylene units linked by three tetra(ethyleneoxy) units. The new cryptand forms a "pseudorotaxane-like" inclusion complex with N,N'-dimethyl-4,4'-bipyridinium bis(hexafluorophosphate) with association constant Ka = 6.1 x 10(4) M-1, 100-fold greater than that of an analogous simple crown ether.

Ethers, Cyclic↗
PubMed1999

Transmyocardial laser revascularisation compared with continued medical therapy for treatment of refractory angina pectoris: a prospective randomised trial. ATLANTIC Investigators. Angina Treatments-Lasers and Normal Therapies in Comparison.

BACKGROUND: Transmyocardial revascularisation (TMR) is an operative treatment for refractory angina pectoris when bypass surgery or percutaneous transluminal angioplasty is not indicated. We did a prospective randomised trial to compare TMR with continued medication. METHODS: We recruited 182 patients from 16 US centres with Canadian Cardiovascular Society Angina (CCSA) score III (38%) or IV (62%), reversible ischaemia, and incomplete response to other therapies. Patients were randomly assigned TMR and continued medication (n=92) or continued medication alone (n=90). Baseline assessments were angina class, exercise tolerance, Seattle angina questionnaire for quality of life, and dipyridamole thallium stress test. We reassessed patients at 3 months, 6 months, and 12 months, with independent masked angina assessment at 12 months. FINDINGS: At 12 months, total exercise tolerance increased by a median of 65 s in the TMR group compared with a 46 s decrease in the medication-only group (p<0.0001, median difference 111 s). Independent CCSA score was II or lower in 47.8% in the TMR group compared with 14.3% in the medication-only group (p<0.001). Each Seattle angina questionnaire index increased in the TMR group significantly more than in the medication-only group (p<0.001). INTERPRETATION: TMR lowered angina scores, increased exercise tolerance time, and improved patients' perceptions of quality of life. This operative treatment provided clinical benefits in patients with no other therapeutic options.

Aged↗
PubMed1999

Serum lysozyme activity can differentiate infection from rejection in organ transplant recipients.

BACKGROUND: The presentation of infection in immunocompromised patients can be subtle. Patients often undergo extensive testing and empiric treatment for rejection and infection while awaiting the results of the biopsy and culture results. Delay in diagnosis of either entity can result in a worse clinical outcome. Lysozyme activity has been found to be both a sensitive and a specific marker for infection in laboratory animals and trauma patients. Our goal was to determine whether lysozyme activity could serve as a reliable marker for infection in immunocompromised organ transplant recipients. METHODS: Transplant recipients from three clinical categories were enrolled in this study. Group 1 (n = 16) were patients hospitalized for sepsis (culture-positive), and Group 2 (n = 13) for biopsy-proven rejection. Group 3 (n = 51) were recipients who had routine blood sampling in the clinic. In Groups 1 and 2, blood was collected within 24 h of hospital admission and centrifuged, and serum samples were stored at 80 degrees C until processing. Lysozyme activity was assayed by turbidimetric measurement on a sample of a standard suspension (0.15 mg/ml) of Micrococcus lysodeikticus in buffer using a spectrophotometer to read the optical density at 450 nm. The lysozyme activity level was then determined by the measuring activity at 1 min subtracted from activity at 4 min. White blood cell count was determined by using a flow cytometer. Statistical comparisons between groups were made using paired Student's t test. RESULTS: Serum lysozyme was found to be significantly elevated in Group 1; the mean level of activity was 60.1 +/- 13 (P < 0.05) compared to the level of activity in Group 2, mean 41.1 +/- 11, and Group 3, mean 40.8 +/- 13. A level of 45 units of activity/ml of serum or above indicated infection and not rejection in the patients admitted to the hospital. CONCLUSIONS: These findings indicate that the lysozyme activity assay appears to be useful in differentiating infection from rejection in transplant recipients.

Adolescent↗
PubMed1999

Scoring of skin rejection in a swine composite tissue allograft model.

BACKGROUND: For the first time, we define and correlate visual and histologic grading systems of composite tissue allograft (CTA) skin rejection in a large-animal model and determine the utility of these grading systems for early diagnosis and monitoring of rejection. MATERIALS AND METHODS: Sixteen pairs of outbred swine underwent transplant of a forelimb osteomyocutaneous free flap. Group I (n = 6) did not receive immunosuppressive therapy. Group II (n = 10) received oral cyclosporin A, mycophenolate mofetil, and prednisone. The flap was visually inspected and protocol skin biopsies were taken at frequent intervals over a 90-day period. Visual Grades 0 (no rejection) to 4 (severe rejection) were assigned based on skin color, bleeding from biopsy site, and blister formation. Histologic Grades 0 to 4 were assigned based on the degree of vasculitis, folliculitis, dermal inflammation, and epidermal degeneration present. RESULTS: All Group I animals progressively rejected their graft by Day 7. Group II grafts survived from 19 and 90 days; 93% of 115 biopsy specimens were read to be within +/-1 histologic score of their assigned flap visual grade. Visual assessment carried an 8% false positive and 39% false negative rate with regard to biopsy-proven rejection. However, 81% of missed rejection specimens were histologic Grade 1. Biopsy, when visually indicated, would detect all rejection episodes when histologically Grade 1 or 2 and still potentially reversible. CONCLUSIONS: Visual scoring of CTA skin serves as a useful tool for initially detecting rejection, but repeated histologic evaluation is necessary for monitoring the subsequent course of the graft.

Animals↗
PubMed1999

Holmium:YAG laser transmyocardial revascularization relieves angina and improves functional status.

BACKGROUND: Transmyocardial revascularization (TMR) surgery uses laser channeling of diseased myocardium to treat ischemia and angina. Rigorous prospective randomized studies have been previously unavailable. METHODS: Forty-three patients were randomized to a medication group and 43 to a group scheduled for TMR surgery and medication. All had advanced cardiac ischemia with CCSA class 3 or 4 angina, took at least 2 cardiac medications at maximum doses, and were ineligible for angioplasty or bypass. RESULTS: Forty-two of 43 TMR group patients received surgery and were discharged after hospitalizations averaging 3.2 days. Two suffered perioperative MIs, with one death. Four others died within 12 months of surgery, 3 from cardiac events and 1 from pneumonia. Five medical group patients died from cardiac events within 12 months. Three, 6, and 12 month exams showed angina class improvement in TMR patients compared to preoperative values (3.86 +/- 0.05 vs 1.71 +/- 0.2, P < 0.0001), and to controls at 12 months (3.77 +/- 0.07 vs 1.71 +/- 0.2, P < 0.0001). Exercise tolerance improved in TMR patients over preoperative values, and was better than medication group scores after 12 months (490 +/- 17 sec. vs 294 +/- 12 sec., p = 0.0002). CONCLUSIONS: Holmium:YAG laser channeling of the myocardium improves function and reduces angina in advanced cardiac patients who lack alternative therapeutic options.

Angina Pectoris↗