Endoscopic treatment of Barrett esophagus

The purpose of the treatment of Barrett epithelium in the distal oesophagus is to reduce or even eliminate the increased risk of malignant degeneration in it. This can be achieved by removing the Barrett epithelium, whether or not dysplastic, and to have it replaced by normal squamous epithelium. Drug treatment or surgical antireflux treatment of Barrett epithelium has hardly any effect on the length of the Barrett epithelium or on the occurrence of malignancy. Various forms of endoscopic ablative therapy (laser coagulation, multipolar electrocoagulation, photodynamic therapy and argon plasma coagulation), in combination with antireflux treatment enable removal of the Barrett epithelium with regeneration of squamous epithelium. However, islets of Barrett epithelium may be found beneath the regenerated squamous epithelium and there is also the possibility of malignant potential of pluripotent stem cells left behind in the oesophagus. Future studies will have to afford insight into long-term results, the costs, the side effects of the various methods of treatment and the quality of life of patients during and after treatment of the Barrett oesophagus.     

Transmural care. A new approach in the care for terminal cancer patients: its effects on re-hospitalization and quality of life

The pharmacological properties of non-adrenergic non-cholinergic (NANC) inhibitory neurotransmission were investigated in the rabbit choledocho-duodenal junction (CDJ), using the microelectrode and tension recording methods. L-NAME (10(-4) M) and apamin (5 X 10 (-6) M) suppressed NANC relaxation evoked by electrical field stimulation (EFS) in the presence of atropine and guanethidine (each 10(-6) M) to a similar extent (to about 40% of the initial control). However, combined application of L-NAME (10(-4) M) and apamin (5 X 10(-6) M) did not abolish it. EFS also evoked biphasic inhibitory junction potentials (IJPs) consisting of initial fast and slow sustained components in the presence of atropine and guanethidine (each 10(-6) M). Apamin (5 X 10(-8)-5 X 10(-6) M) dose-dependently suppressed the initial fast component by about 70%. In contrast, L-NAME (10(-4) M) did not affect either the amplitude of IJP or the resting membrane potential. PACAP-38 (> 10(-8) M) dose-dependently hyperpolarized the smooth muscle membrane of rabbit CDJ followed by a slow repolarization to the original level. After pretreatment with apamin (5 X 10(-7) M), PACAP-38 (10(-6) M) failed to evoke membrane hyperpolarization. During repolarization in the continued presence of PACAP-38, the amplitude of initial fast component of IJP was reduced to about 40-60% of control value, while that of the slow one was unaffected. A similar suppression of initial fast component of IJP (about 40% of the control value) also occurred after application of PACAP (6-38), a PACAP antagonist, or prolonged treatment with monoclonal antibodies to PACAP-27 or PACAP-38. Furthermore, the substantial part of residual fast IJP in the presence of PACAP (6-38) was suppressed by desensitization to alpha,beta-methylene ATP (10(-3) M). These results indicate that in rabbit CDJ NANC relaxation consists mainly of apamin- and L-NAME-sensitive components, which occur in a membrane potential dependent (through membrane hyperpolarization) and independent fashion, respectively. It has further been suggested that PACAP, together with a smaller contribution of ATP, may be involved as the principal apamin-sensitive transmitter in NANC relaxation of this muscle.     

The force-frequency relationship is altered in regenerating and senescent rat skeletal muscle

Maximal tetanic tension was elicited at 200, 150, and 150 Hz in control tibialis anterior muscles and at 150, 100, and 100 Hz in 14-day regenerating muscles of young (3 months), adult (18 months), and old (31 months) Fischer 344/Brown Norway F1 rats, respectively. In contrast to young rats, increasing stimulation frequency from 50 to 150 Hz did not elicit significantly greater tetanic tension in control or regenerating muscles of old rats. At higher stimulation frequencies, tetanic fade was prevalent in control and regenerating muscles of adult (250-300 Hz) and old rats (200-300 Hz), but was only present at 14 days of recovery in regenerating muscles of young rats (300 Hz). The decreased efficacy of rehabilitative and physical medicine procedures in adult and elderly patients who have suffered skeletal muscle injury could be explained, in part, by the postulate that tetanic fade is indicative of inadequate synaptic transmission.     

Bioengineering of a novel small diameter polyurethane vascular graft with covalently bound recombinant hirudin

Development of a small diameter prosthetic vascular graft with surface based antithrombin properties should aid in maintaining early graft patency in small vessel reconstruction. The purpose of this study was to bind covalently a basecoat protein (canine serum albumin [CSAJ) and a potent antithrombin agent (recombinant hirudin [rHir]) to 4 mm inner diameter poly(carbonate urea) urethane grafts with reactive carboxylic acid groups (cPU). 125I-CSA was covalently bound to 1 cm length segments of cPU grafts using the carbodimide cross-linker, 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide hydrochloride (EDC). To bind 125I-rHir covalently, CSA was modified with the heterobifunctional cross-linker sulfosuccinimidyl 4-(N-maleimidomethyl) cyclohexane-1-carboxylate (sulfo-SMCC) before linkage to the cPU surface with EDC (cPU-CSA-SMCC). 125I-rHir was modified with Traut's reagent and reacted with the cPU-CSA-SMCC surface, covalently linking 125I-rHir to surface bound CSA. 125I-CSA binding to the cPU graft surface (34,235 ng/segment) was ninefold, sevenfold, and 10-fold greater than controls with nonspecifically bound 125I-CSA. Covalent linkage of 125I-rHir to the cPU-CSA-SMCC surface (9,974 ng/segment) was 172, 192, and 142-fold greater than controls with nonspecifically bound 125I-rHir. Surface antithrombin properties were characterized using a chromogenic assay to measure residual thrombin activity. Evaluation of surface antithrombin activity showed significantly greater 131I-thrombin inhibition and binding by the cPU surface with covalently bound 125I-rHir, as compared with controls. Release of 125I-rHir from the cPU surface was minimal as compared with controls. Therefore, rHir can be covalently linked to a novel small diameter polyurethane vascular graft surface while maintaining its potent antithrombin properties.     

Classification and treatment of the juvenile idiopathic inflammatory myopathies

This article reviews the current status of the classification and treatment of the juvenile idiopathic inflammatory myopathies. The intent of classification is to define homogeneous groups that share similar clinical features, disease courses, and responses to therapy. The classification scheme proposed includes clinicopathologic subsets, serologic subjects based on the presence of myositis-specific and myositis-associated autoantibodies, and environmental triggers of myositis. Juvenile dermatomyositis is the most common and widely recognized of these disorders. The second part reviews the history of treatment of juvenile dermatomyositis and discusses agents to consider for patients with refractory disease, unacceptable steroid toxicity, or poor prognostic factors.     

Osteoma of the long bones and the spine. A study of eleven patients and a review of the literature

The clinical features, radiographic and histopathological findings, treatment, and results are described for eleven patients who were managed for an extracranial osteoma at our medical center between 1980 and 1993. Ten of the patients were initially seen because of dull, aching bone pain that had been present for two weeks to thirty years. Radiographs demonstrated single or multiple homogeneous, well defined, radiodense foci with smooth round or lobulated margins. The histopathological features consistently included uniformly dense, compact, cortical-like, mature lamellar bone. The preoperative diagnosis was unclear for all patients, and osteoma was rarely considered in the differential diagnosis. For four patients, a tentative diagnosis of osteosarcoma was made, and a wide excision was carried out in two of these patients. Marginal excision with less than three millimeters of normal tissue around the lesion was performed in most patients. None of the osteomas recurred, and ten patients had relief of the pain. Awareness of the clinical, radiographic, and histopathological features of osteoma, as described, is valuable for making a differential diagnosis and for distinguishing osteomas from other lesions.     

Improving the prediction of visual field progression in glaucoma using spatial processing

AIMS: To estimate the cost of population screening for haemochromatosis in Australia and to compare the cost of alternative screening strategies. METHODS: The costs of screening for haemochromatosis were analysed in a hypothetical study using transferrin saturation as the primary screening test, with confirmation of the diagnosis by either liver biopsy or DNA testing for the recently-described haemochromatosis gene. RESULTS: Screening, with confirmation of the diagnosis by liver biopsy, would cost between US$5079 and US$8813 per case detected (excluding administrative costs), depending on the screening strategy (Aust$ = US$0.80). If a DNA test were used instead of liver biopsy, the cost would be reduced to an estimated US$3954-US$4410 per case. This would be further reduced to US$2457 by detection of additional cases by screening family members. The least costly strategy utilised a transferrin saturation threshold of 55% and DNA testing for confirmation of the diagnosis; however, a transferrin saturation threshold of 45% increased the cost only marginally. The initial screening step (transferrin saturation) accounted for 74%-94% of the estimated cost of the screening programme. CONCLUSIONS: Screening for haemochromatosis using transferrin saturation involves relatively modest costs which may be recovered if complications of haemochromatosis can be prevented by early detection and treatment. The most cost-effective strategies utilised transferrin saturation for initial screening, followed by DNA testing. Reduction in the cost of transferrin saturation would lead to a significant reduction in total screening costs. Additional benefits of a screening programme include detection of other iron overload disorders and iron deficiency.     

In vitro development of Ascaris suum from third- to fourth-stage larvae and detection of metabolic antigens in multi-well culture systems

A population of early to late third-stage larvae (L3) of Ascaris suum obtained from the lungs of swine 7 days after infection developed to the fourth stage (L4) in stationary, multi-well, culture plates in an atmosphere of 5% CO2 in air. Larval survival, growth and morphogenesis were evaluated in five culture systems consisting of Dulbecco's Modified Eagles' Medium alone (DM) or containing a serum supplement (DM-S) or a tripeptide (1-glycyl-1-histidyl-1-lysine) at final concentrations of 20, 200, and 1,000 ng/ml (respectively, DM-20, DM-200, and DM-1,000). The rate of development and morphogenesis of larvae from L3 to L4 was optimal in the DM-S culture system and similar to that observed in vivo. However, development beyond L4 was retarded in vitro; sex was not distinguished until 21 days in culture (DIC) and the largest L4 obtained after 52 DIC was 9.2 mm long. Although larval growth and development were similar in all systems tested through 14 days in culture, higher yields of advanced stages of L4 were obtained in systems DM-200 and DM-S. Developing larvae released metabolic products into the culture media that stimulated a specific blastogenic response in lymphocytes obtained from A. suum-infected swine.     

High resolution structure of the N-terminal domain of tissue inhibitor of metalloproteinases-2 and characterization of its interaction site with matrix metalloproteinase-3

The high resolution structure of the N-terminal domain of tissue inhibitor of metalloproteinases-2 (N-TIMP-2) in solution has been determined using multidimensional heteronuclear NMR spectroscopy, with the structural calculations based on an extensive set of constraints, including 3132 nuclear Overhauser effect-based distance constraints, 56 hydrogen bond constraints, and 220 torsion angle constraints (an average of 26.9 constraints/residue). The core of the protein consists of a five-stranded beta-barrel that is homologous to the beta-barrel found in the oligosaccharide/oligonucleotide binding protein fold. The binding site for the catalytic domain of matrix metalloproteinases-3 (N-MMP-3) on N-TIMP-2 has been mapped by determining the changes in chemical shifts on complex formation for signals from the protein backbone (15N, 13C, and 1H). This approach identified a discrete N-MMP-3 binding site on N-TIMP-2 composed of the N terminus of the protein and the loops between beta-strands AB, CD, and EF. The beta-hairpin formed from strands A and B in N-TIMP-2 is significantly longer than the equivalent structure in TIMP-1, allowing it to make more extensive binding interactions with the MMP catalytic domain. A detailed comparison of the N-TIMP-2 structure with that of TIMP-1 bound to N-MMP-3 (Gomis-Ruth, F.-X., Maskos, K., Betz, M., Bergner, A., Huber, R., Suzuki, K., Yoshida, N., Nagase, H. , Brew, K., Bourne, G. P., Bartunik, H. & Bode, W. (1997) Nature 389, 77-80) revealed that the core beta-barrels are very similar in topology but that the loop connecting beta-strands CD (P67-C72) would need to undergo a large conformational change for TIMP-2 to bind in a similar manner to TIMP-1.     

Quality assurance from the viewpoint of the surgeon

The problem of global standardization, clinical documentation, and confidentiality of methods in quality control are discussed. It is concluded that conventional methods of quality assurance should be further developed in order to avoid investments into administration tools that have not yet proved any effectiveness worldwide. Future developments should be orientated to achieve benefits for the patient and to promote surgical excellence.