The threat of hepatitis B virus recurrence: a sword of Damocles to the liver transplant recipient.
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Biomedical subjects
Publications and source records attributed to T Wright.
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The Clearview Chlamydia assay (Wampole Laboratories, Cranbury, N.J.), the PACE 2 DNA probe assay (GenProbe, San Diego, Calif.), and culture were compared for their abilities to detect Chlamydia trachomatis from cervical specimens in a population with a low prevalence (3.9%) of chlamydial infections. A consensus reference method was used. The consensus reference method defined a positive specimen as one with a positive culture result or positive by both of the two nonculture methods. Of the 940 specimens tested, 37 were positive; 36 were positive by culture, 28 were positive by the PACE 2 assay, and 27 were positive by the Clearview assay, giving sensitivities of 97.3, 75.5, and 72.9%, respectively, and specificities of 100, 97.1, and 98.9%, respectively. There was a direct correlation between the number of inclusion-forming units detected by culture and the ability of the two nonculture methods to detect the positive specimens.
Extracts from the parenchymous leaf-gel of the Aloe vera plant (Aloe barbadensis Miller) were shown to contain glutathione peroxidase (GSHPx) activity. The activity was purified to homogeneity by ion exchange and gel filtration (FPLC) chromatography in the presence of 0.5 mM glutathione. The native enzyme has an apparent molecular weight of 62 kD as determined by gel filtration. In the presence of sodium dodecylsulfate (SDS), the molecular weight was estimated to be about 16 kD as determined by polyacrylamide-gel electrophoresis (SDS-PAGE). The native enzyme is proposed to be constituted of four identical subunits; it also contains one atom of selenium per subunit, as found with most glutathione peroxidases from animal sources. The Km values were determined to be 3.2 mM for glutathione and 0.26 mM for the hydroperoxide substrate, cumene hydroperoxide. The enzyme is competitively inhibited by N, S, bis-FMOC glutathione (Ki = 0.32 mM), a potent inhibitor of glyoxalase II. Inhibitors of glyoxalase I (e.g. S-octylglutathione) have no effect on the peroxidase activity.
Four hundred and eighty-seven total knee arthroplasties were performed by a single surgeon with use of a porous-coated anatomic prosthesis between 1982 and 1989. There were thirty-two clinical failures (7 per cent) due to severe wear of the surfaces of the tibial and patellar polyethylene components. Thirty patients had a revision. The average time to failure of the implant was four and one-half years. The initial clinical symptoms of failure by wear consisted of a painless effusion with a decreased range of motion. Subsequent pain was considered as the criterion for failure necessitating operative intervention. Increased weight and decreased age of the patient and a thinner tibial component were significant predictors of an increased risk of failure (p < 0.01). Examination of retrieved tibial components revealed extensive delamination caused by fracture of the polyethylene at a depth of about one millimeter below the surface. Cracks that had propagated in from the medial and lateral peripheries of the tibial component toward the center of the condyles were also a common finding. It appears that the design of the implant as well as clinical factors (the age and weight of the patient) contributed to the mechanical failure of the polyethylene of these implants.
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Hepatitis B recurrence remains a major problem facing liver transplantation programs. The risk of infection varies depending upon the HBV load. High doses of HBIg may reduce the risk of occurrence but it remains expensive. Finally, apparently new infections may occur posttransplantation, which may have been transmitted by organs or blood from HBsAg (-), HBcAb (+) donors, or may reflect reactivation of latent infections in patients who were HBsAg (-). HCV infections are common in patients undergoing liver transplantation, and HCV infection recurs in > 90% of patients; however, recurrent hepatitis C occurs in less than half of these patients. HCV is not an important cause of fulminant non-A, non-B hepatitis, but appears to be the most common cause of posttransplant hepatitis. So what is in the future? For hepatitis B, we still believe the efficacy of HBIg, and in which patients with hepatitis B HBIg should be used, remains to be defined. The effects of antivirals on posttransplant hepatitis B, as well as in prevention of HBV recurrence, also remain to be determined. In the United States, insurance companies are likely to play an important role in determining the future of transplantation for hepatitis B. Medicare recently excluded patients who were HBsAg (+) from coverage for liver transplantation, and a number of private insurers have subsequently followed suit. For HCV, newer screening tests for the virus are likely to decrease the rate of HCV acquisition following liver transplantation, from the current 35% incidence of HCV acquisition. The impact of antiviral treatment on posttransplant hepatitis remains to be determined and deserves study. Finally, the development of regimens that might allow prevention of recurrent HCV infections in patients undergoing liver transplantation also should be a matter of future study.
In Japan, the presence of a large regenerative nodule within a cirrhotic liver, referred to as a macroregenerative nodule or adenomatous hyperplasia, is thought to play a role in the pathogenesis of hepatocellular carcinoma. These lesions, however, have received little attention outside of Japan. We examined 110 sequentially explanted cirrhotic livers for the presence of such nodules. By gross examination, 19 livers (17.3%) had 40 nodules (10 livers had more than one nodule) between 0.8 and 3.5 cm in diameter. By histological examination, 28 of these were macroregenerative nodules and 12 were hepatocellular carcinomas. Three of these hepatocellular carcinomas, however, appeared to have arisen in association with a macroregenerative nodule. We found that the architectural features of thickened cell plates, formation of trabeculae and loss of reticulin were usually very helpful in differentiating benign macroregenerative nodules from hepatocellular carcinoma. The incidence of macroregenerative nodules in our series was similar to that seen in the Japanese studies, and although we feel that they may play a role in the pathogenesis of carcinoma, we do not believe their presence is necessary for the development of hepatocellular carcinoma.
In a prospective study, synovial fluid metal levels from stainless steel, cobalt-chromium, and titanium-alloy cemented total hip implants were measured. There were 37 well-fixed and 44 loose hip arthroplasties. Tissue-metal levels were quantitated in the cases revised for loosening. Retrieval analysis for implant wear was performed. Synovial fluid analysis showed a fivefold increase in metal levels of loose compared with well-fixed stainless steel implants. There was a sevenfold increase in metal levels of loose compared with well-fixed cobalt-chromium implants. There was a 21-fold increase in metal levels of loose compared with well-fixed titanium-alloy (Ti-6Al-4V) implants. Tissue-metal levels from revised cobalt-chromium implants averaged 45 micrograms/g dry tissue weight compared to 4,470 micrograms/g dry tissue weight from revised titanium-alloy implants, a 100-fold increase. Implant retrieval analysis showed severe burnishing and scratching in all titanium-alloy femoral heads and extensive burnishing and scratching in the majority of the femoral stems. Well-fixed cemented implants have similar low synovial fluid metal levels. However, when loosening of implants occurs, titanium-alloy implants release disproportionate levels of metal into synovial fluid and local tissues compared to stainless steel or cobalt-chromium.
To investigate the hypothesis that an association exists between the presence of metallic particulate or ionic debris released from the components of a total hip replacement and the histologic reaction in the surrounding tissues, cobalt, chromium, nickel, and molybdenum levels were measured in periarticular tissue from 22 individuals who had revision surgery. Total tissue content of the four elements (averaged per case) ranged from 2.7 to 250 micrograms of metal per gr of dried tissue (mean, 39 micrograms/gr); however, within each case, the tissue-metal content varied more widely. The highest total tissue-metal contents occurred in cases revised for infection. Fibrosis, histiocytic reaction, hemorrhage, and necrosis were the most frequent histologic findings. Polyethylene and cement particles each appeared in approximately half of all sections, while microscopic metal particles were seen only in tissues from the infected hips. Tissue-metal content did not correlate with the histologic findings, with any of the demographic variables, nor with duration of implantation. Ratios of the individual constituent elements generally reflected the cobalt-chromium alloy composition, suggesting that metal debris was present predominantly as wear particles. Only for tissues with very low metal contents did departures of these ratios indicate the presence of ionic corrosion products. The extremely low metal contents measured in many cement-bone interfacial tissues and the few metal particles found histologically suggest that metal particles may have been less important in inflammatory reaction and loosening than cement or polyethylene particles.(ABSTRACT TRUNCATED AT 250 WORDS)
A multicentered prospective trial to investigate the usefulness of the AO spinal internal fixator for the treatment of thoracolumbar fractures and fracture-dislocations was undertaken. This pedicle screw-rod system was effective in stabilizing a variety of unstable fracture patterns. It was effective in decompressing the canal of retropulsed bony fragments associated with burst fractures. By the use of this implant, sagittal plane deformity was easily corrected.
We measured lung function and exercise tolerance in 15 adults with moderate kyphoscoliosis (thoracic curvatures between 25 degrees and 70 degrees, mean +/- SD = 46.93 degrees +/- 14.02 degrees). Forced vital capacity showed a slight reduction from values predicted from age and sex matched control subjects (3.39 +/- 1.06 vs 4.06 +/- 0.82 L, p less than 0.05). However, exercise tolerance was significantly lower than previously reported in healthy adults (VO2max = 31.60 +/- 9.12 vs 37.07 +/- 4.91 ml/kg/min, p less than 0.05). Despite the reduced exercise tolerance, the ratio of maximum tidal volume to vital capacity (VTmax/VC) was similar to that observed in healthy adults. The mean dyspnea index (VEmax/MVV) was also normal at 69.4 +/- 19.0. Hypoxic and hypercapnic ventilatory responses were within predicted normal limits at 0.67 +/- 0.37 L/min-1 fall in SaO2-1 and 1.67 +/- 0.92 L/min-1 mm Hg PCO2(-1). We conclude that the impairment of exercise performance found in adults with moderate scoliosis cannot be attributed to any important ventilatory limitation, abnormality in lung volume, or impaired chemoreceptor sensitivity. We suggest that the reduced VO2max likely arises from deconditioning and lack of regular aerobic exercise.
Four cases of patients in whom graft vs. host disease developed after liver transplantation are described. The clinical course of each patient was similar with fever, pancytopenia, diarrhea and a skin rash developing 1 or 2 mo after liver transplantation. The clinical diagnosis was made from skin or colon biopsy specimens. Liver dysfunction did not occur in the patients at the time of diagnosis. Extrahepatic donor DNA was identified in the three patients it was tested for. Three patients died from the complications of the disease primarily related to sepsis. The other patient recovered from the graft vs. host disease but died from lymphoproliferative disease.
Four hundred eighty-seven porous-coated anatomic (PCA) total arthroplasties were performed by the same surgeon between January 1982 and December 1989. Forty-three patients developed an effusion, pain, or decreased range of motion after a period of pain-free function. Average time to onset of symptoms was 4.5 years. Joint fluid aspirations were sterile and revealed the presence of high-density polyethylene crystals, best seen under a polarizing microscope. Thirty-three of these patients were arthroscopically evaluated. Extensive polyethylene wear and delamination were identified. Wear was most extensive on the medial tibial plateau. Patellar polyethylene wear was also identified. Substantial femoral component abrasions were present in areas where exposure of the tibial and patellar base plates had occurred. Diffuse granulomatous synovial tissue revealed an extensive foreign-body giant-cell reaction to polyethylene particles. In all patients, temporary symptomatic relief was obtained after arthroscopy. Thirty-two patients have, subsequently, had revision surgery. Intraoperative findings and biopsies at the time of revision confirmed the arthroscopic observations. Arthroscopy allowed the accurate diagnosis of polyethylene wear, provided temporary symptomatic relief, and facilitated preoperative revision planning. Polyethylene wear in PCA total knee replacements was related to patient characteristics (larger, younger, more active patients), nonconforming femotibial articular surfaces, thin polyethylene, heat-pressed polyethylene, and nonrigid mechanical attachment of polyethylene to metal base plate. Younger, more active, larger patients with total knee arthroplasties should be observed closely for evidence of polyethylene wear.
The expression of type VII collagen and 19-DEJ-1 antigen was examined in 73 and 71 patients, respectively, with recessive dystrophic epidermolysis bullosa (RDEB), comprising gravis, mitis, inversa, and indeterminant subsets, to better determine the specificity and sensitivity of two monoclonal antibodies directed against these dermoepidermal junction-specific epitopes. Type VII collagen (LH 7:2 epitope) was usually absent (in 90%) in patients with the gravis variant of RDEB, whereas its expression was most often diminished (in 67%) in those with the mitis form of the disease. Only 2% and 5% of patients with gravis and mitis variants, respectively, had apparent normal amounts of type VII collagen within their skin. In contrast, six (86%) of seven patients with the inversa variant had normal expression of the antigen. Only 25% of all patients with RDEB lacked the 19-DEJ-1 antigen; of these, however, most had the gravis variant, although absence or diminution was also infrequently observed in those with the mitis and inversa forms. Intermediate findings were noted in patients classified as having indeterminant forms of RDEB. Some variability in antigen expression was also noted among affected siblings. We conclude that assessment of expression of the LH 7:2 epitope of type VII collagen may be diagnostically useful, although considerable overlap does exist between individual patients with gravis and mitis forms. 19-DEJ-1 expression is a far less sensitive probe in RDEB, although such data may prove useful in the assessment of newborns lacking the characteristic features of gravis disease. In addition, based on our experience with inversa RDEB, it would appear that altered expression of type VII collagen cannot be attributed to blister formation in this latter rare subset, since this antigen is usually strongly detected along the dermoepidermal junction, even in perilesional skin sites.
The glucocorticoid receptor belongs to a family of ligand activated nuclear receptors. In addition to steroid hormone receptors, this family also includes receptors for thyroid hormone, retinoic acid and 1,25-dihydroxyvitamin D3 as well as some receptors with as yet unknown ligands, the so called orphan receptors. It is possible that the dioxin receptor is a member of this family as well although this cannot be definitely assessed until the receptor has been cloned. Interestingly, the clofibrate receptor, believed to be involved in clofibrate induction of certain isozymes of cytochrome P-450, has recently been shown to be a member of the steroid receptor supergene family and it is conceivable that other P-450 inducers might act via as yet uncharacterized receptors belonging to the same gene family. Therefore, we should learn significantly about principles of P-450 regulation by considering basic mechanisms of glucocorticoid action; the glucocorticoid receptor probably represents the most extensively studied member of the nuclear receptor family. Our laboratory has been particularly interested in structural aspects of this receptor and has used gene technology to overexpress its different domains, particularly the DNA-binding domain, the structure of which has been resolved using NMR.
Cultural examination of cecal contents from 109 market weight hogs slaughtered in Prince Edward Island during May-July 1988 yielded 62 isolates of Campylobacter coli and seven Campylobacter jejuni. A commercial latex agglutination test helped to confirm the identification of Campylobacter. When tested against four drugs: erythromycin, tetracycline, kanamycin and ampicillin, 11 isolates showed multiple resistance. Resistance to erythromycin was seen in 19% and 28.6% of Campylobacter coli and Campylobacter jejuni respectively. All the isolates were susceptible to nitrofurans, gentamicin and chloramphenicol.
We report a new variant of epidermolysis bullosa simplex (EBS), termed EBS superficialis, which is characterized by the development of skin cleavage just beneath the level of stratum corneum. In two of seven patients identified, a second and more focal cleft within the lower third of the epidermis was also detected. Epidermolysis bullosa simplex superficialis appears to be transmitted as an autosomal dominant trait. It differs from other autosomal dominant forms of EBS by the common findings of milia and atrophic scarring, as well as involvement of oral and/or ocular surfaces. Epidermolysis bullosa simplex superficialis is further differentiated from peeling skin syndrome by the presence of blisters and the absence of spontaneous continual exfoliation or peeling.
With few exceptions, epidermolysis bullosa (EB) simplex is an autosomal dominant disorder characterized by rather localized and recurrent nonscarring blister formation; mucous membranes and other organs are usually uninvolved. Recently, two patients were described with an autosomal recessive form of EB simplex associated with muscular dystrophy. We now describe four additional patients with autosomal recessive EB simplex, three of whom had associated muscular dystrophy or congenital myasthenia gravis. These patients had generalized cutaneous findings, including milia, atrophic scarring, nail dystrophy, and scalp alopecia, which have been classically attributed to either junctional or dystrophic EB. Each patient had significant oral cavity involvement, and in two, marked growth retardation and anemia were also present. Our findings suggest that autosomal recessive EB simplex may be characterized by rather severe cutaneous and extracutaneous disease activity, and may be associated with at least two distinct neuromuscular diseases.