Stemmed femoral knee prostheses: Effects of prosthetic design and fixation on bone loss

Although the revision rates for modern knee prostheses have decreased drastically, the total number of revisions a year is increasing because many more primary knee replacements are being done. At the time of revision, bone loss is common, which compromises prosthetic stability. To improve stability, intramedullary stems are often used. The aim of this study was to estimate the effects of a stem, its diameter and the interface bonding conditions on patterns of the bone remodeling in the distal femur.

We created finite element models of the distal half of a femur in which 4 types of knee prostheses were placed. The bone remodeling process was simulated using a strain-adaptive bone remodeling theory. The amount of such remodeling was determined by calculating the changes in bone mineral density in 9 regions of interest from simulated DEXA scans.

The computer simulation model showed that revision prostheses tend to cause more bone resorption than primary ones, especially in the most distal regions. Predicted long-term bone loss due to a revision prosthesis with a thin stem equalled that around a prosthesis with an intercondylar box. However, strong regional differences were found- the stemmed prostheses having more bone loss in the most distal areas and some bone gain in the more proximal ones. A prosthesis with a thick stem led to an increase in bone loss. When the prosthesis-cement interface was bonded, more bone loss was predicted than with an unbonded interface. These results suggest that a stem which increases stability initially may reduce stability in the long term. This is due to an increase in stress shielding and bone resorption.     

Development of three parallel cytochrome P450 enzyme affinity detection systems coupled on-line to gradient high-performance liquid chromatography.

A high resolution screening (HRS) technology is described, in which gradient high-performance liquid chromatography (HPLC) is connected on-line to three parallel placed bioaffinity detection systems containing mammalian cytochromes P450 (P450s). The three so-called enzyme affinity detection (EAD) systems contained, respectively, liver microsomes from rats induced by beta-naphthoflavone (CYP1A activity), phenobarbital (CYP2B activity), and dexamethasone (CYP3A activity). Each P450-EAD system was optimized for enzyme, substrate, and organic modifier (isopropyl alcohol, methanol, and acetonitrile) in flow injection analysis mode. Characteristic P450 ligands were used to validate the P450-EAD systems. IC(50) values of the ligands were measured and found to be similar to those obtained with conventional microtiter plate reader assays. Detection limits (n = 3; signal-to-noise ratio = 3) of potent inhibitors ranged from 1 to 3 pmol for CYP1A activity, 4 to 17 pmol for CYP2B activity, and 4 to 15 pmol for CYP3A activity. The three optimized P450-EAD systems were subsequently coupled to gradient HPLC and used to screen compound mixtures for individual ligands. Finally, to increase analysis efficiency, a HRS system was constructed in which all three P450-EAD systems were coupled on-line and in parallel to gradient HPLC. The triple parallelized P450-EAD system was shown to enable rapid profiling of individual components in complex mixtures for inhibitory activity to three different P450s.     

Case report: a patient with Hodgkin's disease after treatment for testicular cancer.

A young patient developed Hodgkin's disease 11 years after surgical, chemotherapeutic and radiation treatment for stage IIIA embryonal carcinoma of the testis. The importance is stressed of establishing a tissue diagnosis when there is an unexpected course of the disease.     

Structure-activity relationship between (E)-5-(2-bromovinyl)- and 5-vinyl-1-beta-D-arabinofuranosyluracil (BV-araU, V-araU) in inhibition of Epstein-Barr virus replication.

The structure-activity relationship between (E)-5-(2-bromovinyl)- and 5-vinyl-1-beta-D-arabinofuranosyluracil (BV-araU and V-araU) in inhibition of Epstein-Barr virus (EBV) was evaluated. Both V-araU and BV-araU effectively inhibited EBV replication in virus-producer P3HR-1(LS) cells, as determined by DNA-DNA hybridization. The 50% effective doses (ED50) for viral DNA replication were 0.005 and 0.3 microM for V-araU and BV-araU, respectively. The in vitro therapeutic index was 4000 for V-araU and 1300 for BV-araU. Synthesis of EBV-induced polypeptides with molecular weights of 145,000 (145, 140, 130, and 110 kDa) was significantly inhibited by both drugs. Only V-araU inhibited the synthesis of 85-, 55-, and 32-kDa polypeptides by approx. 50%. Kinetic analysis of inhibition and reversibility of EBV DNA replication after removal of the drugs indicated that BV-araU has a more prolonged inhibitory effect than V-araU. These results indicate that the substitution of H by Br in the 5-vinyl group results in marked reduction in anti-EBV activity while prolonging the drug effect and diminishing cytotoxicity.     

Operative laparoscopy for uterine pathology.

In the first years of its use, operative laparoscopy for uterine pathology was employed in the surgical treatment of myomas and in the correction of uterine retroversion (hysteropexy). More recently the technique has been employed for the laparoscopically assisted hysterectomy or for subtotal laparoscopical hysterectomy using the Semm Kit. Also radical hysterectomy has been performed in advanced centers by laparoscopy. In this paper, the Authors discuss the indications, the counterindications, the risks and complications of the operative laparoscopy in the different forms of ovarian pathology.     

Urinary excretion of glycated albumin in insulin-dependent diabetic patients with micro- and macroalbuminuria.

Non-enzymatic glycosylation (glycation) involves both circulating proteins, such as albumin and structural proteins, such as the components of the glomerular basement membrane. Glycated albumin is more anionic than unmodified plasma albumin at physiologic pH. Preferential urinary excretion of glycated proteins has occasionally been reported in diabetes. We therefore investigated the selectivity index (renal clearance of non-glycated/glycated albumin) in 25 insulin-dependent diabetic patients (17 with microalbuminuria and 8 with macroalbuminuria), and 19 healthy subjects. The selectivity index was significantly higher (p less than 0.01) in the microalbuminuric patients than in the macroalbuminuric patients and the control subjects: 1.11 +/- 0.03 SEM vs 0.94 +/- 0.08 vs 0.98 +/- 0.02. These results are not consistent with preferential urinary excretion of glycated albumin in insulin-dependent diabetic patients with increased urinary albumin excretion.     

Microvascular function in viable myocardium after chronic infarction does not influence fractional flow reserve measurements.

Fractional flow reserve (FFR) is an index of coronary stenosis severity. FFR is the ratio of hyperemic myocardial flow in the stenotic area to maximal flow in that same territory without stenosis and can be measured with a pressure wire. In patients with prior infarction, measuring FFR in infarct-related arteries may be different for 2 reasons: a smaller mass of viable myocardium depending on the stenotic infarct-related artery and greater microvascular resistance in the infarcted area than in the reference area. When microvascular resistance does not differ between the infarcted and the reference areas, FFR should equal relative flow reserve (RFR). RFR is the ratio of myocardial blood flow in the stenotic area to blood flow in a normally perfused reference area, at maximal hyperemia. H(2)(15)O PET measures myocardial flow within only the viable areas of an infarct and can be used to measure RFR. The present study assessed in patients with chronic myocardial infarction whether microvascular resistance in the infarct is different from that in the reference area. Therefore, the correlation between FFR and RFR using H(2)(15)O PET was studied. METHODS: In the catheterization laboratory, FFR was measured in the infarct-related artery and a reference coronary artery. The H(2)(15)O PET study and FFR measurements were performed on the same day in 22 patients. RESULTS: In 27 patients, the mean interval between the PET study and infarction was 3.3 y. Most patients had an anterior infarction, and the mean ejection fraction was 44%. The mean FFR and RFR values were 0.75 +/- 0.16 and 0.74 +/- 0.18, respectively. A significant correlation (r = 0.81; P < 0.0001) was found between FFR and RFR. The linear regression line was close to the line of identity. CONCLUSION: In patients with chronic myocardial infarction and a reduced ejection fraction, a good correlation was found between FFR measurements in the infarct-related artery and RFR. Because the linear regression line between FFR and RFR was close to the line of identity, one can conclude that microvascular resistance in the viable myocardium does not differ from that in the reference area.