Surface properties of Indonesian-made narrow dynamic compression plates.

The enormous need of orthopaedic (surgical) implants such as osteosynthesis plates is difficult to be fulfilled in developing countries commonly rely on imported ones. One of the alternatives is utilization of local resources, but only after they have been proven safe to use, to overcome this problem. Surface properties are some of the determining factors of safety for those implants. We have succeeded in developing prototype of osteosynthesis plate and the results indicate that Indonesian-made plates need improvement with regards to the surface quality of physical characterization.

Evaluation of measures to decrease intra-operative bacterial contamination in orthopaedic implant surgery.

The aim of this study was to evaluate whether behavioural and systemic measures will decrease intra-operative contamination during total hip or knee replacements. The influence of these measures on subsequent prolonged wound discharge, superficial surgical site infection and deep periprosthetic infection was also investigated during an 18-month follow-up period. Four swabs were taken from instruments at the beginning and end of the procedure for 207 procedures. Removed bone material (acetabulum and femur in case of the hip joint; femur and tibia in case of the knee joint) was also tested for contamination. Initially, 70 operations performed under original control conditions were included, after which the first behavioural measure was introduced (i.e. better use of the plenum). Cultures were taken during 67 operations using better use of the plenum (Group 1), followed by disciplinary measures and the installation of a new laminar flow system. Seventy operations were monitored after this second intervention (Group 2). The control group showed intra-operative contamination in 32.9% (23/70) of cases, Group 1 showed contamination in 34.3% (23/67) of cases and Group 2 showed contamination in 8.6% (6/70) of cases. Prolonged wound discharge and superficial surgical site infection decreased significantly in Group 2, as did the incidence of deep periprosthetic infection; however, the latter did not reach statistical significance. This study shows that the combination of systemic and behavioural changes in an operating room significantly decreases the incidence of intra-operative bacterial contamination, subsequent prolonged wound discharge and superficial surgical site infection. After 18 months of follow-up, there was also a decrease in deep periprosthetic infection.

Review article: similarities and differences among delayed-release proton-pump inhibitor formulations.

Proton-pump inhibitors are acid-labile, and require an enteric coating to protect them from degradation in the stomach when given orally. However, this leads to delayed absorption and onset of action of the proton-pump inhibitor. This article aims to review the similarities and differences between the various formulations of delayed release proton-pump inhibitors. Delayed-release omeprazole and delayed-release lansoprazole have been suspended in sodium bicarbonate for tube administration; however, for omeprazole, absorption is further impaired and antisecretory effects are disappointing. Although such formulations may be more convenient for clinical use in certain patient groups, absorption of the proton-pump inhibitor is still influenced by residual enteric coating. There are few differences among the currently available delayed-release proton-pump inhibitors with respect to their pharmacodynamic effects during chronic administration. There are minor formulation-based pharmacokinetic differences among these agents, primarily reflected in their bioavailability following the first few doses. Differences in bioavailability may explain slight differences in the rate of onset of maximal antisecretory effect. However, minor pharmacodynamic and pharmacokinetic differences are not associated with meaningful differences in clinical outcomes.

Digital correction of magnification in pelvic x rays for preoperative planning of hip joint replacements: theoretical development and clinical results of a new protocol.

The introduction of digital radiological facilities leads to the necessity of digital preoperative planning, which is an essential part of joint replacement surgery. To avoid errors in the preparation and execution of hip surgery, reliable correction of the magnification of the projected hip is a prerequisite. So far, no validated method exists to accomplish this. We present validated geometrical models of the x-ray projection of spheres, relevant for the calibration procedure to correct for the radiographic magnification. With help of these models a new calibration protocol was developed. The validity and precision of this procedure was determined in clinical practice. Magnification factors could be predicted with a maximal margin of error of 1.5%. The new calibration protocol is valid and reliable. The clinical tests revealed that correction of magnification has a 95% margin of error of -3% to +3%. Future research might clarify if a strict calibration protocol, as presented in this study, results in more accurate preoperative planning of hip joint replacements.

Bacterial survival in the interfacial gap in gentamicin-loaded acrylic bone cements.

Clinical experience indicates the beneficial effects of antibiotic-loaded bone cement. Although in vitro studies have shown the formation of a biofilm on its surface they have not considered the gap between the cement and the bone. We have investigated bacterial survival in that gap. Samples with gaps 200 microm wide were made of different bone cements. These were stored dry ('pre-elution') or submersed in phosphate-buffered saline to simulate the initial release of gentamicin ('post-elution'). The gaps were subsequently inoculated with bacteria, which had been isolated from infected orthopaedic prostheses and assessed for their sensitivity to gentamicin. Bacterial survival was measured 24 hours after inoculation. All the strains survived in plain cements. In the pre-elution gentamicin-loaded cements only the most gentamicin-resistant strain, CN5115, survived, but in post-elution samples more strains did so, depending on the cement tested. Although high concentrations of gentamicin were demonstrated in the gaps only the gentamicin-sensitive strains were killed. This could explain the increased prevalence of gentamicin-resistant infections which are seen clinically.

Disopyramide-induced urinary retention. Report of nine cases and review of the literature.

Urinary retention is sometimes reported as an adverse reaction during disopyramide phosphate therapy. We report one case of acute renal failure and eight cases of urinary retention. Previous reports of this adverse reaction are summarized. The cause of disopyramide-induced urinary retention is unknown. It is possible that disopyramide or a metabolite via their anticholinergic properties plays some role in the manifestation of urinary tract symptomatology. Treatment of this adverse reaction includes lowering the dose, discontinuing the drug, or possibly using a cholinergic drug to compete with the anticholinergic effects of the disopyramide.

Life-threatening interactions between HIV-1 protease inhibitors and the illicit drugs MDMA and gamma-hydroxybutyrate.

Human immunodeficiency virus 1 (HIV-1) protease inhibitors have dramatically reduced the morbidity and mortality due to HIV-1 infection. However, most of these antiretrovirals are also potent inhibitors (and occasionally inducers) of hepatic and intestinal cytochrome P450 systems and, therefore, have the potential to alter the elimination of any substance that utilizes these metabolic pathways. We describe a patient infected with HIV-1 who was treated with ritonavir and saquinavir and then experienced a prolonged effect from a small dose of methylenedioxymetamphetamine (MDMA or ecstacy) and a nearly fatal reaction from a small dose of gamma-hydroxybutyrate (GHB). We also discuss the potential for HIV-1 protease inhibitors to alter the metabolism of other abusable prescribed and illicit substances.

Single and multiple doses of oral cimetidine do not change liver blood flow in humans.

Liver blood flow was measured in 10 healthy men for 6 hours after single (300 mg) and multiple (300 mg every 6 hours for 5 days) oral doses of cimetidine. Blood flow measurements were determined in the superior mesenteric and hepatic arteries and in the intrahepatic branches of the portal and hepatic veins by use of a duplex Doppler ultrasound technique. Compared with baseline measurements obtained before drug administration, cimetidine treatment did not change blood flow in any of the four blood vessels. Cimetidine serum concentrations and pharmacokinetic parameters were similar to those reported in other studies conducted in healthy adults. The findings of this study indicate that single and multiple 300 mg doses of oral cimetidine do not change liver blood flow.

Changes in antipyrine and indocyanine green kinetics during nifedipine, verapamil, and diltiazem therapy.

Ten healthy subjects received oral antipyrine and intravenous indocyanine green (ICG) alone and after 5 days of oral nifedipine, diltiazem, and verapamil. Antipyrine clearance decreased during verapamil (range 4% to 26%) and diltiazem (6% to 24%) therapy (P less than 0.001) but did not change during nifedipine treatment. Antipyrine t1/2 also increased during verapamil and diltiazem treatment (P less than 0.001). ICG clearance did not change during diltiazem therapy but increased during dosing with nifedipine and verapamil (P less than 0.05). Estimated liver blood flow (derived from ICG clearance and hematocrit) also increased during verapamil (mean 33%) and nifedipine (mean 27%) treatment (P less than 0.05). Drug interactions with other liver-metabolized drugs may occur during therapy with these calcium antagonists. Nifedipine appears to increase liver blood flow whereas diltiazem inhibits oxidative drug metabolism. Drug interactions with verapamil could involve both mechanisms.

Antibiotic use after cefuroxime prophylaxis in hip and knee joint replacement.

The amount of additional antibiotics measured by defined daily dose (DDD) methods after 2651 hip and 362 knee replacements was assessed after prophylaxis with one or three doses (1502/1511 patients) of cefuroxime. No differences were observed between the two regimens with respect to total amount, type, indication, and duration of additional antibiotics. The incidence of joint sepsis did not differ significantly between the two trial arms, but the sample was too small for definite conclusions. There were 11.4 DDD/100 bed days of additional antibiotics used in 21% of patients after hip replacement and 15.7 DDD/100 bed days in 31% after knee replacement. For wound problems, 3.8 and 6.9 DDD/100 bed days were given in the hip- and knee-replacement groups. For distant infection, 6.5 DDD/100 bed days was administered in both groups. Duration of therapy varied only in relation to indication. Prescribed were penicillins (43% to 50%), sulfonamides (18%), cephalosporins (10% to 16%), and nitrofurantoin (8% to 13%); drug use was related to the type of infection.

The effects of oral nifedipine on hepatic blood flow in humans.

Duplex ultrasonography was used to measure changes in hepatic blood flow in 13 healthy volunteers after they received single doses of 10 mg oral nifedipine and placebo. Blood flow was measured in the hepatic artery and branches of the portal and hepatic veins at baseline and 0.3, 0.6, 1, 1.5, 2, 3, 4, and 5 hours after drug administration. Cardiac output was also measured at baseline and 1, 2, and 3 hours after dosing. Blood flow initially increased in all three vessels 0.6 hour after administration of nifedipine (29%, 56%, and 31% in the hepatic artery, hepatic vein, and portal vein, respectively) compared with placebo. Flow rapidly returned to baseline in the hepatic artery and hepatic vein, whereas it appeared to remain elevated through 3 hours in the portal vein. Nifedipine administration resulted in an increase in cardiac output of 26%, 22%, and 14% above placebo at 1, 2, and 3 hours, respectively. No significant differences were detected in the systolic, diastolic, or mean arterial blood pressures after nifedipine or placebo. This study demonstrates that nifedipine increases hepatic blood flow in a transient nature and systemic hemodynamic parameters do not necessarily reflect specific organ responses. The nifedipine-induced change in blood flow should be considered when nifedipine is coadministered with high-clearance drugs, because systemic availability may be increased.

Disposition of drugs in cystic fibrosis. II. Hepatic blood flow.

To determine whether the increased clearance of high extraction-ratio drugs in cystic fibrosis is caused by an increase in hepatic blood flow, the blood flow in main branches of the hepatic vein and portal vein was measured by use of noninvasive duplex ultrasound scanning in 10 adult subjects with cystic fibrosis and in 10 healthy age-, gender-, and height-matched control subjects. No statistically significant differences between subjects with cystic fibrosis and control subjects were detected in either the hepatic vein (217 +/- 103 ml/min for subjects with cystic fibrosis versus 211 +/- 135 ml/min for control subjects) or the portal vein (205 +/- 114 ml/min for subjects with cystic fibrosis versus 190 +/- 101 ml/min for control subjects) blood flows. These data indicate that a large (greater than or equal to 100%) increase in the clearance of high extraction-ratio drugs in patients with cystic fibrosis is unlikely to be primarily caused by an increase in hepatic blood flow. It is probable that alternative mechanisms such as enhanced secretory or metabolic pathways account in large part for increases in clearance of high extraction-ratio drugs.

Scintigraphic detection of bone and joint infections with indium-111-labeled nonspecific polyclonal human immunoglobulin G.

The utility of indium-111-(111In) labeled immunoglobulin G (IgG) to detect infection of bone and adjacent tissues was investigated. Proof of infection was obtained by cultures taken at surgery. All 32 patients showed focally increased uptake on the technetium-99m- (99mTc) methylene diphosphonate (MDP) skeletal scintigraphies. Labeled immunoglobulin correctly identified presence, location, extent and soft-tissue involvement of the suspected inflammatory site. In these patients, focally increasing accumulation was noted over 48 hr. Discrimination between infection and sterile inflammatory lesions was not possible. Two fractures, 6-mo-old, and an aseptic loosening of a total-hip prosthesis were not visualized. Side effects after the immunoglobulin administration were not observed. Radiolabeled immunoglobulin is a new and safe radiopharmaceutical for the investigation of infectious bone and joint disease. The sensitivity of this agent appears at least as high as that of labeled leukocytes. However, labeled immunoglobulin can easily be prepared in every nuclear medicine department.

Nuclear arthrography: combined scintigraphic and radiographic procedure for diagnosis of total hip prosthesis loosening.

UNLABELLED: Radiographic arthrography and bone scintigraphy are common diagnostic procedures used for evaluating total hip prostheses. In this study, both techniques are combined, and nuclear contrast imaging (nuclear arthrography) is added. The efficacy of the procedures is evaluated. METHODS: After intravenous injection of 99mTc-methylene diphosphonate (MDP), standard radiographic arthrography was performed in 105 patients (107 prostheses). The radiographic contrast medium was mixed with insoluble 111In-colloid (5 MBq/20 ml). After completion of the radiographic arthrography, nuclear arthrography was performed, and multiple-view dualisotope images (111In, 247-keV peak only) were recorded. Images were interpreted by superposition of the 111In image and the corresponding 99mTc-MDP image, the latter serving as a landmark for the position of the prosthesis and osseous structures. Findings at surgery were used as the gold standard. RESULTS: In both cemented and uncemented acetabular and femoral components, nuclear arthrography performed better than or equal to radiographic arthrography (70%-90% and 60%-75%, respectively). Nuclear arthrography had higher diagnostic accuracy than 99mTc-MDP images alone. CONCLUSION: Nuclear arthrography is a sensitive technique for detection of loosening of prostheses, offering added value over radiographic arthrography and bone scanning alone, especially for evaluation of the femoral component. Radiographic arthrography remains necessary not only for adequate deposition of contrast agents but also for detailed evaluation of osseous structures.

Fluorine-18-fluorodeoxyglucose assessment of glucose metabolism in bone tumors.

UNLABELLED: In our study, we investigate the glucose metabolism of various types of bone lesions with 18F-fluorodeoxyglucose (FDG) PET. METHODS: Twenty-six patients showing clinical and radiographic symptoms of a malignant bone tumor were included. Histological examination after the PET study revealed 19 malignant and 7 benign tumors. PET images were corrected for attenuation. Arterial blood samples were taken to establish the input function. The metabolic rate of glucose consumption (MRglc) was calculated for the whole tumor, for the 10 pixels with maximum activity and for contralateral normal muscle tissue. RESULTS: All lesions were clearly visualized with 18F-FDG PET except for a small infarction of the humerus. All the other lesions had increased glucose metabolism compared to surrounding and contralateral muscle tissue. Both maximum and average MRglc for benign, as well as malignant, lesions were significantly higher than for contralateral normal tissue. The maximum and average MRglc were not higher for malignant as opposed to benign lesions. There was a large overlap between the MRglc of benign and malignant lesions. CONCLUSION: Fluorine-18-FDG PET appears suitable to visualize bone tumors. With the quantification of glucose metabolism, it is not possible to differentiate between benign and malignant bone tumors. There does not seem to be a clear correlation between the MRglc and the biologic aggressiveness of the neoplasms.

Cytotoxic, allergic and genotoxic activity of a nickel-titanium alloy.

The nearly equiatomic nickel-titanium (NiTi) alloy is known for its shape memory properties. These properties can be put to excellent use in various biomedical applications, such as wires for orthodontic tooth alignment and osteosynthesis staples. The aim of this study was to evaluate the short-term biological safety of the NiTi alloy. We carried out an end-point dilution minimal essential medium (MEM) extract cytotoxicity test, a guinea-pig sensitization test and two genotoxicity tests: the Salmonella reverse mutation test and the chromosomal aberration test. The NiTi alloy showed no cytotoxic, allergic or genotoxic activity, similar to the clinical reference control material AISI 316 LVM stainless steel. This promising biological behaviour was most likely due to a minimal release of ions and in that way a reflection of the good corrosion resistance of the NiTi alloy. Given these very good results, together with the good tissue compatibility as shown in several implantation studies in the literature, the NiTi alloy can be regarded as a biologically safe implant material with many promising clinical applications.

Backgrounds of antibiotic-loaded bone cement and prosthesis-related infection.

Antibiotic-loaded bone cement has been in use for over 30 years for the fixation of total joint arthroplasties, although its mechanism of action is still poorly understood. This review presents the backgrounds of bone cements, prosthesis-related infection and antibiotic-loaded bone cements. It is shown that antibiotic-loaded bone cement has a significant effect on bacteria, particularly in animal and clinical studies. However, recently, antimicrobial resistance among bacteria has been ascribed to the antibiotic-loaded bone cement. The unresolved issues both regarding the action of antibiotic-loaded bone cement and the nature of the antimicrobial resistance necessitate further research into the interaction of antibiotic-loaded bone cement and bacteria.

Staphylococcus aureus biofilm formation on different gentamicin-loaded polymethylmethacrylate bone cements.

In this in vitro study, the formation of a Staphylococcus aureus biofilm on six gentamicin-loaded bone cements (CMW1, CMW3, CMW Endurance, CMW2000, Palacos, and Palamed) was determined in a modified Robbins device over a 3 days time span and related with previously (Van de Belt et al., Biomaterials 21 (2000) 1981) measured kinetics of antibiotic release by these cement brands. The influence of gentamicin release on biofilm formation was quantified by expressing the number of colony-forming units on gentamicin-loaded cement relative to the number of viable organisms on unloaded cement of the same brand. Biofilms formed on all gentamicin-loaded cements, despite the release of antibiotics, followed a consistent pattern in time with a maximum number of colony-forming units per unit cement area found between 24 and 30 h after inoculation. None of the gentamicin-loaded cements showed a reduction in biofilm formation relative to unloaded cements within 6 h after inoculation, whereas only gentamicin-loaded CMW1 and Palacos reduced biofilm formation 24 h after inoculation. Alternatively, CMW Endurance, CMW2000, and Palamed did not exhibit any initial reductions in biofilm formation, but effects started after 72, 48, and 72 h, respectively. Biofilm reduction by gentamicin-loaded CMW3 lasted the longest from 24 to 72 h. Interestingly, each cement seemed to have a different "window-of-effectiveness" with regard to reduction in biofilm formation that did not relate with the gentamicin-release kinetics. Summarising, this study demonstrates that although gentamicin loading of bone cements yields reductions in biofilm formation, S. aureus is able to grow on gentamicin-loaded bone cements.

Surface roughness, porosity and wettability of gentamicin-loaded bone cements and their antibiotic release.

In this study, the release of gentamicin as a function of time was measured for six different gentamicin-loaded bone cements and related with the surface roughness, porosity and wettability of the cements. Initial release rates varied little between the six bone cements (CMW1, CMW3, CMW Endurance, CMW 2000, Palacos, and Palamed) and ranged from 8.6 to 14.1 microg/cm2/h. The total amounts of gentamicin released after 1 week varied between 4.0 and 5.3% of the total amount of antibiotic incorporated for the CMW cements and was 8.4% for Palacos. Palamed released after 1 week significantly more of the gentamicin incorporated (17.0%). The wettability of all cements was similar (water contact angles between 70 and 80 degrees), but the surface roughness and the porosity of the cements varied markedly. Initial release rates increased with surface roughness, although the correlation coefficient was low (0.64), while total amounts released increased linearly (correlation coefficient 0.97) with the bulk porosity of the cements. Consequently, it can be concluded that the release kinetics of gentamicin from bone cements is controlled by a combination of surface roughness and porosity.