Use of acetabular models in planning complex acetabular reconstructions

The number of patients requiring revision total hip arthroplasty continues to increase each year. Accurate preoperative planning is a key factor in obtaining a good result. Radiographs provide little information concerning the actual extent of the acetabular defects. Computed tomography-generated models of the acetabulum can provide the surgeon with accurate information concerning the size and location of the defects. Evaluation of radiographs and models in 24 cases showed that radiographs alone failed to detect all 13 anterior wall defects (P < .001), 8 of 18 posterior wall defects (44.4%, P < .001), and 8 of 19 segmental central defects (42%, P < .001), all of which were easily identified with the models. This study showed that preoperative planning based on the foam models accurately predicted the actual implant used in 22 of 24 cases (92%).     

Differential class III and glibenclamide effects on action potential duration in guinea-pig papillary muscle during normoxia and hypoxia/ischaemia

1. Microelectrode recording techniques were used to study the effects of several potassium channel blockers which are considered to be Class III antiarrhythmic compounds. The effects of (+)-sotalol, UK-66,914, UK-68,798 and E-4031 on action potential duration (APD) were determined in guinea-pig isolated papillary muscles. The compounds were evaluated under normoxic or hypoxic/ischaemic conditions at 36.5 degrees C and compared to glibenclamide, which is considered to be a blocker of ATP-dependent potassium channels. Prolongation of action potential duration at 90% repolarization (APD90) was taken as an indirect measure of potassium channel blockade. 2. Under normoxic conditions, the Class III compounds prolonged APD in a concentration-dependent manner. According to EC15 values, the order of potency of the Class III compounds was found to be UK-68,798 > E-4031 > UK-66,914 > (+)-sotalol. Glibenclamide did not significantly prolong APD90 under normoxic conditions. 3. Perfusion with an experimental hypoxic or ischaemic bathing solution produced qualitatively similar effects on action potentials. Over a period of 20-25 min in either of the experimental solutions, there was a small decrease in action potential amplitude (APA) and a prominent shortening of APD. The ischaemic solution also depolarized the resting membrane potential by about 15 mV. 4. (+)-Sotalol and UK-66,914 did not reverse the shortening of APD induced by perfusion with hypoxic Krebs solution. High concentrations of glibenclamide (10 microM) and UK-68,798 (30 and 60 microM) partially reversed the hypoxia-shortened APD. Glibenclamide was more potent and exhibited a greater time-dependent action than UK-68,798. 5. During experimental ischaemia, the Class III compound E-4031 (10 microM, n = 7) produced small, but significant, increases in the APD90 (11 +/-3 ms after 20 min) which were not clearly time-dependent(14 +/- 4 ms after 30 min). UK-68,798 (10 microM) also produced a small, but insignificant, increase in APD90(12 =/-6 ms at 20 min, n = 4). Higher concentrations of UK-68,798 (30 and 60 microM, n = 4) did not produce a consistently significant increase in APD90 during ischaemia: significance was only attained after 20 min in the presence of 60 microM UK-68,798 (24 +/- 12 ms). However, in marked contrast to the effects of the Class III compounds, glibenclamide (10 microM) produced large time-dependent increases in ischaemic APD90 (34 +/- 11 ms at 7 min, n = 9) which were significant 15 min or more after drug addition(52 +/- 12 ms at 20 min, n = 7; 74 +/- 5 ms at 30 min, n = 6).6. The present microelectrode data suggest that blockers of ATP-dependent potassium channels, such as glibenclamide, might prove to be more effective than Class III compounds against ischaemia-induced shortening of cardiac action potentials.     

Urinary obstruction

Radiologic imaging is commonly used in the diagnosis, classification, and follow-up of renal obstruction. Precise definitions of the elements of urinary obstruction are critical. This article examines the physiology of renal obstruction and the use of such imaging tests as excretory urogram, retrograde pyelography, antegrade pyelography, Whitaker test, ultrasound, CT scan, MR imaging, and radionuclide renography.     

Postsurgical wound progression monitored by temporal changes in the expression of matrix metalloproteinase-9

It is important to monitor the early stages of postoperative wound repair in order to identify those problems associated with impaired healing. Many of the crucial cellular responses of early wound healing, such as inflammatory infiltration, angiogenesis and re-epithelialization, are made possible through the action of matrix metalloproteinases (MMPs). Expression of MMP-2 and MMP-9 is elevated in acute wounds, and still greater levels are found in chronic wounds, indicating that uncontrolled proteolysis is a characteristic of retarded healing. Therefore, comparative measurements of MMPs may be used to monitor the progression of early wound healing. To investigate this, wound fluids and sera were collected from mastectomy and colectomy patients throughout early stages of repair, and the temporal expression profile established. Wounds which were healing were expressed maximal levels of MMP-9 at 24 h, followed by a significant decline by 48 h. Persistent elevation of MMP-9 expression was associated with infected and chronic wounds, and was identified in postoperative wounds by the absence of the significant decline between 24 and 48 h. Measurement of MMP-9 in postoperative wound fluids, therefore, provides an early indicator of impaired healing, which may be evaluated non-invasively within 48 h of closure.     

Cellular mechanisms underlying carbachol-induced oscillations of calcium-dependent membrane current in smooth muscle cells from mouse anococcygeus

1. At a holding potential of -40 mV, carbachol (50 microM) produced a complex pattern of inward currents in single smooth muscle cells freshly isolated from the mouse anococcygeus. Membrane currents were monitored by the whole-cell configuration of the patch-clamp technique. Previous work has identified the first, transient component as a calcium-activated chloride current (ICl(Ca)) and the second sustained component as a store depletion-operated non-selective cation current (I(DOC)). The object of the present study was to examine the cellular mechanisms underlying the third component, a series of inward current oscillations (I(oscil)) superimposed on I(DOC). 2. Carbachol-induced I(oscil) (amplitude 97 +/- 11 pA; frequency 0.26 +/- 0.02 Hz) was inhibited by the chloride channel blocker anthracene-9-carboxylic acid (A-9-C; 1 mM), and by inclusion of 1 mM EGTA in the patch-pipette filling solution. 3. In calcium-free extracellular medium (plus 1 mM EGTA), carbachol produced an initial burst of oscillatory current which lasted 94 s before decaying to zero; I(oscil) could be restored by re-admission of calcium. The frequency, but not the amplitude, of I(oscil) increased with increasing concentrations of extracellular calcium (0.5-10 mM). 4. Inclusion of the inositol triphosphate (IP3) receptor antagonist heparin (5 mg ml(-1) in the patch-pipette filling solution, or pretreatment of cells with the sarcoplasmic reticulum (SR) calcium ATPase inhibitor cyclopiazonic acid (CPA; 10 microM), prevented the activation of I(oscil) by carbachol. Caffeine (10 mM) activated both ICl(Ca) and I(DOC) and prevented the induction of I(oscil) by carbachol. Caffeine and CPA also abolished I(oscil) in the presence of carbachol, as did both a low (3 microM) and a high (30 microM) concentration of ryanodine. 5. Carbachol-induced I(oscil) was abolished by the general calcium entry blocker SKF 96365 (10 MM) and by Cd2+ (100 microM), but was unaffected by La3+ (400 microM). As found previously, I(DOC) was also blocked by SKF 96365 and Cd2+, but not La3+; the inhibition of I(DOC) preceded the abolition of I(oscil) by 27 s with SKF 96365 and by 30 s with Cd2+. Nifedipine (1 microM) produced a partial inhibition of the carbachol-induced I(oscil) frequency at holding potentials of -20 mV and -60 mV and, in addition, reduced I(DOC) at -60 mV by 18%. 6. It is concluded that carbachol-induced inward current oscillations in mouse anococcygeus cells are due to a calcium-activated chloride current, and reflect oscillatory changes in cytoplasmic calcium ion concentration. These calcium oscillations are derived primarily from the SR stores, but entry of calcium into the cell is necessary for store replenishment and maintenance of the oscillations. Capacitative calcium entry (via I(DOC) appears to be important not only for sustained contraction of this tissue, but also as a route for re-filling of the SR and, therefore, represents an important target for the development of novel and selective drugs.     

From genome to proteome: protein map of Haemophilus influenzae

High-resolution two-dimensional (2-D) polyacrylamide gel electrophoresis allows the separation of complex biological mixtures (i.e., several hundred proteins from a bacterial cell lysate) in a single experiment. In this report proteins from Haemophilus influenzae were separated by 2-D gels and analyzed by peptide mass fingerprinting and/or amino acid analysis. By comparing the peptide mass profiles and the amino acid composition with the Haemophilus influenzae database, 119 protein spots were identified. The combination of amino acid analysis and peptide mass fingerprinting is a powerful tool for a rapid and economical identification of a large number of proteins resolved by 2-D gels. Studies on gene regulation and changes of protein expression upon drug treatment require quick and serial analysis techniques to efficiently identify potential new drug targets.     

Detection of hepatitis G virus from serum and liver of a patient with long-term liver dysfunction after autologous bone marrow transplantation

Long-term effects after blood or bone marrow transplantation (BMT) are emerging as an important issue, as more patients are included in BMT programmes and as this procedure becomes more successful. Long-term liver dysfunction, mainly due to chronic graft-versus-host disease or hepatitis C virus infection, is a well-known complication. Nevertheless, the diagnosis of liver disease in this patient group is sometimes difficult and, despite adequate studies, it may remain undetected. A novel hepatitis-associated virus, hepatitis G virus (HGV), has recently been identified. The virus belongs to the Flaviviridae family and is known to be parenterally transmitted, although there is no clear evidence to implicate this agent in causing acute or chronic hepatitis. We report a patient who developed mild, but persistent, abnormalities in transaminases for 2 years after an autologous BMT. HGV RNA was detected in both serum and liver. HGV RNA persisted in serum for at least 8 months. No other known hepatitis virus was found. This report provides the first direct evidence of a patient with long-term liver abnormalities after a BMT in whom the only known hepatitis virus isolated was the HGV.