[Reconsideration of the indications for unicompartmental knee arthroplasty].

Unicompartmental knee arthroplasty (UKA), a procedure that has gradually emerged in recent years, is considered an effective treatment for resolving knee pain and restoring good function due to its significant clinical advantages. In the 1980s, Kozinn and Scott proposed the classic indications as selection criteria to identify ideal candidates for UKA. However, as treatment concepts, surgical instruments, surgical techniques, and prosthesis designs for this disease have improved, these indications proposed more than 30 years ago appear too limited, leading to some limitations in the widespread use of UKA. Specifically, surgeons have offered new perspectives on issues related to obesity, age, patellofemoral arthritis, severe varus deformity of the knee, anterior cruciate ligament deficiency, flexion contracture, failed high tibial osteotomy and post-traumatic arthritis. For this reason, this article will briefly discuss modern perspectives involving the indications for UKA based on current evidence with the aim of providing a reference for the reader.

Polydatin alleviates osteoporosis by enhancing the osteogenic differentiation of osteoblasts.

OBJECTIVE: Osteoporosis is a severe degenerative chronic metabolic bone disease associated with high fracture risk. Polydatin (PD), a major bioactive component of Polygonum cuspidatum, has antioxidant and anti-inflammatory effects. This study investigated the anti-osteoporotic activity of PD in ovariectomized (OVX) mice and elucidated its underlying molecular mechanisms. SUBJECTS AND METHODS: An osteoporosis mouse model was established using OVX mice. OVX mice were then administered 10 or 40 mg/kg of PD for 60 days. Micro-CT and three-point bending tests were used to determine the therapeutic activities of PD in OVX mice. H&E staining was used to determine whether PD induced hepatorenal toxicity. In addition, the cellular and molecular mechanisms underlying the functionality of PD were elucidated. RESULTS: Micro-CT results showed that compared to control mice, the bone mass of OVX mice was significantly reduced due to estrogen deficiency; however, PD administration significantly elevated bone mass. Furthermore, PD substantially improved the trabecular microstructure parameters of the femur and enhanced bone strength compared with OVX mice. Hepatorenal toxicity was not observed in liver and kidney samples stained with H&E. PD significantly increased the proliferation of pre-osteoblast MC3T3-E1 cells and upregulated the expression of osteogenic differentiation markers compared to those in controls, as determined by qRT-PCR and western blotting. CONCLUSIONS: PD exerted a significant anti-osteoporotic effect in OVX mice by promoting osteogenesis. PD has great potential as a therapeutic option for osteoporosis.

[Lateral unicompartmental knee arthroplasty: challenges and hopes].

There is a low prevalence of osteoarthritis in the lateral compartment of the knee, but the overall number of domestic patients is large, and lateral unicompartmental arthroplasty (UKA) has good prospects.The unique anatomical structure and kinematic characteristics of the lateral compartment make the surgical operation more challenging.Traditional UKA patients have a high incidence of lower limb mal-alignment and poor prosthetic position, which leads to limit of their promotion and application.In recent years, with the development of treatment concepts, surgical techniques and materials, the survival time of UKA prosthesis has been continuously extended, and the clinical effect has been continuously optimized.Strictly grasp the surgical indications in radiology, anatomy and clinical manifestations, familiarize with the lateral compartment anatomy and biomechanical features, and master the technical details are the prerequisites and guarantees for the success of the lateral UKA.With the advancement of technology, minimal invasion, precision and individuation should be the goal pursued for lateral UKA surgery.

Evaluation of mandibular contour in patients with significant facial asymmetry.

Most previous studies on facial asymmetry have not specifically differentiated mandible deviation from structural asymmetry of the mandible. The purpose of this study was to assess the symmetry of the mandible by examining its contour in a cohort of patients with significant facial asymmetry. Eleven cases of facial asymmetry with chin deviation ≥10mm were enrolled. A voxel-paired median plane (optimal symmetry plane, OSP) and two landmark-based median planes were generated. The OSP was created by computing the best pairing of the bony voxels on the two sides. One side of the mandibular contour was mirrored onto the other side using the test plane. The contour differences were measured by distance and by area ratio. They were examined both in frontal and frontal downward inclined view. The contour symmetry of the mandible was that revealed by the plane that presented the best symmetry. The results showed that the OSP worked best in bisecting the contour into two symmetrical halves. Contour analysis showed relatively small discrepancies between the two sides. In conclusion, the mandibles retained an acceptable contour symmetry despite the presence of significant mandibular deviations. It is suggested that proper mandibular alignment be the primary objective in the correction of facial asymmetry.

A summary of recent findings on birth outcomes and developmental effects of prenatal ETS, PAH, and pesticide exposures.

Inner-city minority populations are high-risk groups for adverse birth outcomes and also more likely to be exposed to environmental contaminants, including environmental tobacco smoke (ETS), benzo[a]pyrene B[a]P, other ambient polycyclic aromatic hydrocarbons (global PAHs), and residential pesticides. The Columbia Center for Children's Environmental Health (CCCEH) is conducting a prospective cohort study of 700 northern Manhattan pregnant women and newborns to examine the effects of prenatal exposure to these common toxicants on fetal growth, early neurodevelopment, and respiratory health. This paper summarizes results of three published studies demonstrating the effects of prenatal ETS, PAH, and pesticides on birth outcomes and/or neurocognitive development [Perera FP, Rauh V, Whyatt RM, Tsai WY, Bernert JT, Tu YH, et al. Molecular evidence of an interaction between prenatal environment exposures on birth outcomes in a multiethnic population. Environ Health Perspect 2004;12:630-62; Rauh VA, Whyatt RM, Garfinkel R, Andrews H, Hoepner L, Reyes A, et al. Developmental effects of exposure to environmental tobacco smoke and material hardship among inner-city children. Neurotoxicol Teratol 2004;26:373-85; Whyatt RM, Rauh V, Barr DB, Camann DE, Andrews HF, Garfinkel R, et al. Prenatal insecticide exposures, birth weight and length among an urban minority cohort. Environ Health Perspect, in press]. To evaluate the effects of prenatal exposure to ETS, PAHs, and pesticides, researchers analyzed questionnaire data, cord blood plasma (including biomarkers of ETS and pesticide exposure), and B[a]P-DNA adducts (a molecular dosimeter of PAHs). Self-reported ETS was associated with decreased head circumference (P = 0.04), and there was a significant interaction between ETS and adducts such that combined exposure had a significant multiplicative effect on birth weight (P = 0.04) and head circumference (P = 0.01) after adjusting for confounders. A second analysis examined the neurotoxic effects of prenatal ETS exposure and postpartum material hardship (unmet basic needs in the areas of food, housing, and clothing) on 2-year cognitive development. Both exposures depressed cognitive development (P < 0.05), and there was a significant interaction such that children with exposure to both ETS and material hardship exhibited the greatest cognitive deficit (7.1 points). A third analysis found that cord chlorpyrifos, and a combined measure of cord chlorpyrifos, diazinon, and propoxur-metabolite, were inversely associated with birth weight and/or length (P < 0.05). These results underscore the importance of policies that reduce exposure to ETS, air pollution, and pesticides with potentially adverse effects on fetal growth and child neurodevelopment.

beta-Scruin, a homologue of the actin crosslinking protein scruin, is localized to the acrosomal vesicle of Limulus sperm.

Scruin (alpha-scruin) is an actin bundling protein found in the acrosomal process of Limulus polyhemus sperm. We have cloned and sequenced a second scruin isoform from Limulus, beta-scruin, that is 67% identical to alpha-scruin. Northern and Southern analyses confirm that beta-scruin and alpha-scruin are encoded by distinct genes. The sequence of beta-scruin, like alpha-scruin, is organized into N- and C-terminal superbarrel domains that are characterized by a six-fold repeat of a 50 residue motif. Western analysis using rabbit polyclonal antisera specific for alpha- and beta-scruin indicate that beta-scruin, like alpha-scruin, is found in Limulus sperm but not blood or muscle. Both immunofluorescence microscopy and immunogold-EM localize beta-scruin within the acrosomal vesicle at the anterior of sperm but not in the acrosomal process. The function of beta-scruin in this membrane-bounded compartment that is devoid of actin is unknown. However, the location of beta-scruin together with the fact that it contains two putative beta-superbarrel structural folds, which are known to be catalytic domains in a number of proteins, suggests it may have a possible enzymatic role.

Two microtubule-associated proteins required for anaphase spindle movement in Saccharomyces cerevisiae.

In many eucaryotic cells, the midzone of the mitotic spindle forms a distinct structure containing a specific set of proteins. We have isolated ASE1, a gene encoding a component of the Saccharomyces cerevisiae spindle midzone. Strains lacking both ASE1 and BIK1, which encodes an S. cerevisiae microtubule-associated protein, are inviable. The analysis of the phenotype of a bik1 ase1 conditional double mutant suggests that BIK1 and ASE1 are not required for the assembly of a bipolar spindle, but are essential for anaphase spindle elongation. The steady-state levels of Ase1p are regulated in a manner that is consistent with a function during anaphase: they are low in G1, accumulate to maximal levels after S phase and then drop as cells exit mitosis. Components of the spindle midzone may therefore be required in vivo for anaphase spindle movement. Additionally, anaphase spindle movement may depend on a dedicated set of genes whose expression is induced at G2/M.

Characterization of caveolin-rich membrane domains isolated from an endothelial-rich source: implications for human disease.

Caveolae are 50-100-nm membrane microdomains that represent a subcompartment of the plasma membrane. Previous morphological studies have implicated caveolae in (a) the transcytosis of macromolecules (including LDL and modified LDLs) across capillary endothelial cells, (b) the uptake of small molecules via a process termed potocytosis involving GPI-linked receptor molecules and an unknown anion transport protein, (c) interactions with the actin-based cytoskeleton, and (d) the compartmentalization of certain signaling molecules, including G-protein coupled receptors. Caveolin, a 22-kD integral membrane protein, is an important structural component of caveolae that was first identified as a major v-Src substrate in Rous sarcoma virus transformed cells. This finding initially suggested a relationship between caveolin, transmembrane signaling, and cellular transformation. We have recently developed a procedure for isolating caveolin-rich membrane domains from cultured cells. To facilitate biochemical manipulations, we have applied this procedure to lung tissue--an endothelial and caveolin-rich source-allowing large scale preparation of these complexes. These membrane domains retain approximately 85% of caveolin and approximately 55% of a GPI-linked marker protein, while they exclude > or = 98% of integral plasma membrane protein markers and > or = 99.6% of other organelle-specific membrane markers tested. Characterization of these complexes by micro-sequencing and immuno-blotting reveals known receptors for modified forms of LDL (scavenger receptors: CD 36 and RAGE), multiple GPI-linked proteins, an anion transporter (plasma membrane porin), cytoskeletal elements, and cytoplasmic signaling molecules--including Src-like kinases, hetero-trimeric G-proteins, and three members of the Rap family of small GTPases (Rap 1--the Ras tumor suppressor protein, Rap 2, and TC21). At least a fraction of the actin in these complexes appeared monomeric (G-actin), suggesting that these domains could represent membrane bound sites for microfilament nucleation/assembly during signaling. Given that the majority of these proteins are known molecules, our current studies provide a systematic basis for evaluating these interactions in vivo.

Identification of I-plastin, a human fimbrin isoform expressed in intestine and kidney.

The complete cDNA sequence of human intestine-specific plastin (I-plastin) was determined from a clone derived by PCR. It consists of a 97-bp 5' untranslated region, a 1,887-bp coding region, and a 1,655-bp 3' untranslated region. The coding region predicts a 629-residue polypeptide whose sequence displays 86, 75, and 73% identities with chicken intestine fimbrin, human T-plastin, and human L-plastin, respectively. Recombinant I-plastin cross-linked actin filaments into bundles in the absence but not in the presence of calcium. The I-plastin gene was mapped by PCR to human chromosome 3; the L- and T-plastin genes were previously mapped to chromosomes 13 and X, respectively. I-plastin mRNA was detected in the small intestine, colon, and kidneys; relatively lower levels of expression were detected in the lungs and stomach. In contrast, L-plastin expression was restricted to the spleen and other lymph node-containing organs, while T-plastin was expressed in a variety of organs, including muscle, brain, uterus, and esophagus. In contrast to the situation for the intestine, high levels of L- and T-plastin mRNAs were detected in Caco-2, a human colon-derived cell line. Immunofluorescence microscopy detected I-plastin in the brush border of the small intestine and colon. These results identify I-plastin as the human homolog of chicken intestine fimbrin and as a third plastin isoform in humans.

Iontophoresis of hydrocortisone across hairless mouse skin: investigation of skin alteration.

The effects of hydration, sodium dodecyl sulfate (SDS), and electric current on the permeability of hairless mouse skin was examined in vitro with a neutral solute, hydrocortisone, as a permeant. The study was carried out by pretreating the skin with (1) normal saline, (2) 0.06% SDS in 0.3% NaCl, (3) normal saline plus 0.5 mA anodic current, and (4) 0.06% SDS in 0.3% NaCl plus 0.5 mA anodic current for 8 h. The pretreated skin was then immediately used for passive or anodic transport of hydrocortisone. Results show that pretreatment of skin with either normal saline or 0.06% SDS resulted in a slightly increased passive penetration of hydrocortisone with a prolonged lag time, but did not significantly change the anodic transport of hydrocortisone. There was no significant difference between normal saline pretreatment and 0.06% SDS pretreatment, indicating that 0.06% SDS did not irreversibly alter the permeability of skin other than its hydration effect. Pretreatment of skin with current, and especially with current combined with 0.06% SDS, yielded a significant increase in both passive and anodic transport of hydrocortisone with reduced lag time, indicating that alteration of the skin structure had occurred. The reversibility of this alteration depends on the duration of exposure of the skin to the electric field. Short-term exposure (< 2 h) does not appear to change the permeability of skin in any significant way; long-term exposure may lead to slowly reversible or irreversible skin alteration.

Stability of fentanyl citrate and bupivacaine hydrochloride in portable pump reservoirs.

The stability of fentanyl citrate and bupivacaine hydrochloride in an admixture with 0.9% sodium chloride injection in portable pump reservoirs with or without overwraps was investigated. Twelve 100-mL samples containing fentanyl 20 micrograms/mL and bupivacaine hydrochloride 1250 micrograms/mL were placed in the plastic drug reservoirs, and 1-mL quantities were withdrawn immediately after preparation and at intervals during 30 days of storage. Six reservoirs were refrigerated (3 degrees C) and six stored at room temperature (23 degrees C); three at each temperature were placed in overwraps. All samples were observed for precipitation and for change in color or pH and were analyzed for drug concentration by high-performance liquid chromatography. No precipitation or change in color or pH was observed during the 30-day storage period. No loss of fentanyl or bupivacaine was detected in either the wrapped or the unwrapped samples. Fentanyl citrate and bupivacaine hydrochloride in 0.9% sodium chloride injection appear to be compatible, and admixtures containing the two drugs at the concentrations studied can be stored without overwraps for up to 30 days at refrigerated or room temperature without any significant loss of potency.

Stability of fentanyl citrate in 0.9% sodium chloride solution in portable infusion pumps.

The stability of fentanyl citrate diluted with 0.9% sodium chloride injection for use in portable infusion pumps was studied. The commercially available injection containing 50 micrograms of fentanyl per milliliter was diluted to a concentration of 20 micrograms/mL. Twelve 100-mL portions of the dilute solution were placed in polyvinyl chloride infusion pump drug reservoirs; six were stored at 3 degrees C and six at 23 degrees C; three at each temperature were overwrapped with polypropylene-Mylar. Initially and after 5, 10, 20, and 30 days of storage, 1-mL samples were taken from each reservoir, inspected for color change and precipitation, and assayed for fentanyl concentration by high-performance liquid chromatography. Initially and on day 30, pH of the samples was checked. No precipitation or change in color or pH was observed. No substantial decrease in fentanyl concentration was found in either the wrapped or unwrapped samples at either temperature, although concentrations on day 30 in the samples at 23 degrees C were slightly lower than those at 3 degrees C. Under the conditions studied, fentanyl citrate solutions containing 20 micrograms of fentanyl per milliliter can be stored for 30 days in polyvinyl chloride reservoirs for portable infusion pumps.

Effect of pH on the equilibrium dialysis of phenytoin suspension with and without enteral feeding formula.

Significant decreases have been reported in phenytoin absorption when the suspension is combined with continuous enteral feedings. Several theories for this interaction have been proposed including binding of phenytoin to the protein constituents of the enteral formula, phenytoin binding to the calcium in the enteral formula, and inadequate dissolution of the suspension when delivered with the enteral formula due to the high pKa of phenytoin and the acidic nature of the enteral formula. We therefore evaluated the effects of pH levels 2.0, 3.5, 6.0, and 8.0 on the interaction of phenytoin suspension with enteral formula (Osmolite) with equilibrium dialysis using a Spectra/Por 1 (MWCO 6000-8000) molecularporous dialysis membrane. Phenytoin concentrations in the dialysis membrane (internal phase) mimicked the expected stomach concentrations of a 100-mg dose administered in an adult stomach containing 200 ml of gastric fluid. External phase buffers were sampled at 0.5, 1.0, 2.0, 4.0, 8.0, 12.0, and 24.0 hr after the start of the dialysis. The phenytoin concentrations in the external phase were compared between buffer alone or buffer combined with enteral formula at the same pH and time intervals. With pH 2.0 and 3.5 the enteral formula formed an aggregate with suspension whereas no aggregate was formed with pH 6.0 and 8.0. The phenytoin concentrations with pH 2.0 were 26% to 44% lower and with pH 3.5 were 11.5 to 27% lower when phenytoin suspension was combined with enteral solution. However, at 24 hr there was no difference between the two conditions with both pH 2.0 and 3.5.(ABSTRACT TRUNCATED AT 250 WORDS)

Recovery of phenytoin suspension after in vitro administration through percutaneous endoscopic gastrostomy Pezzer catheters.

Various methods of administering phenytoin suspension through a percutaneous endoscopic gastrostomy (PEG) Pezzer catheter were evaluated in vitro to determine which method resulted in the most complete recovery of phenytoin. To determine the effect of temperature on phenytoin recovery, 12 mL of phenytoin suspension (Dilantin-125, 125 mg/5 mL) was administered through three separate 35.5-cm 20 French latex PEG Pezzer catheters under each of three temperature conditions (suspension 11.8 degrees C and catheter 22 degrees C, suspension and catheter 22 degrees C, and suspension 22 degrees C and catheter 37 degrees C). To determine the effect of the administration method, 12-mL aliquots of phenytoin suspension were injected into the catheter by seven methods that varied with respect to catheter temperature, dilution of suspension, and irrigation of catheter. Each method was tested in triplicate, and samples were assayed by high-performance liquid chromatography. Varying the temperature of the catheter or suspension had little effect on the recovery of phenytoin. There was no appreciable loss of phenytoin when the suspension was undiluted, regardless of whether the catheter was irrigated. The greatest losses were seen when the suspension was diluted before administration. Irrigation also caused a decrease in recovery, but to a lesser extent than dilution. Until the effects of administering multiple doses of phenytoin through PEG Pezzer catheters are investigated, phenytoin suspension should not be diluted before administration because of decreased recovery and increased administration time.

Nefopam hydrochloride degradation kinetics in solution.

A stability-indicating reversed-phase high performance liquid chromatographic method was developed for the detection of nefopam hydrochloride and its degradation products under accelerated degradation conditions. The degradation kinetics of nefopam hydrochloride in aqueous solutions over a pH range of 1.18 to 9.94 at 90 +/- 0.2 degrees C was studied. The degradation of nefopam hydrochloride was found to follow apparent first-order kinetics. The pH-rate profile shows that maximum stability of nefopam hydrochloride was obtained at pH 5.2-5.4. No general acid or base catalysis from acetate, phosphate, or borate buffer species was observed. The catalytic rate constants on the protonated nefopam imposed by hydrogen ion and water was determined to be 7.16 X 10(-6) M-1 sec-1, and 4.54 X 10(-9) sec-1, respectively. The pKa of nefopam hydrochloride in aqueous solution was determined to be 8.98 +/- 0.33 (n = 3) at 25 +/- 0.2 degrees C by the spectrophotometric method. The catalytic rate constant of hydroxyl ion on the degradation of nefopam in either protonated or nonprotonated form was determined to be 6.63 X 10(-6) M-1 sec-1 and 4.06 X 10(-6) M-1 sec-1, respectively. A smaller effect of hydroxyl ion on the degradation of nonprotonated than on the degradation of protonated nefopam was observed.(ABSTRACT TRUNCATED AT 250 WORDS)

Uptake of trimethoprim and metronidazole in the seminal vesicle: experimental study.

A rat model for determining drug levels in the seminal vesicle was developed. In separate studies, trimethoprim and metronidazole were injected intravenously into rats and assays of seminal vesicle, plasma, and prostate performed. Drug levels were detected early in both the seminal vesicle and prostate. This appears to be the first study to report drug levels in the seminal vesicle. Metronidazole levels in the seminal vesicle were very low and short lived.

Degradation mechanism of nefopam in solution under stressed storage conditions.

Nefopam, in pH 2.0 and pH 9.0 solutions, was forcibly degraded at 90 +/- 0.2 degrees C for 60 days. At least eight degradation products from the above solutions were collected from a reverse-phase high performance liquid chromatographic (HPLC) system with a C18 semipreparative column. Some minor peaks were considered insignificant, and no attempt was made to collect and identify their structures. The collected eluents under each major peak were further purified by extraction with methylene chloride from alkaline solutions. Proton nuclear magnetic resonance and fast atom bombardment mass spectroscopy were used to characterize the chemical properties of these degradates. The chemical structures of the major degradation products were proposed as (B) or (C) 2,3-dihydro-2(2'-hydroxyethyl)-N-methyl-1-phenyl-isoindole; (D) or (E) 1-hydroxy-3,4,5,6-tetrahydro-5-methyl-1-phenyl-1H-2,5-benzoxazocine++ +; (F) 2-(N-(2-hydroxyethyl)-N-methylaminomethyl) benzhydrol; (G) 2-(N-(2-hydroxyethyl)-N-methylaminoethyl) benzophenone; (H) 1-hydroxy-3,4,5,6-tetrahydro-5-methyl-1-phenyl-1H-2,5-benzoxazocine++ +, where B and C, D and E, are diasteromers. The possible pathways by which the nefopam degradation proceeded in acidic and basic solutions is postulated as Schemes I and II, respectively. The initial ring-opening process at the site of ether linkage appears to be the rate-determining step of degradation in both acidic and basic solutions.

Stability of fluorouracil administered through four portable infusion pumps.

The stability of fluorouracil in four portable infusion pumps under simulated infusion conditions was studied. Three commercially available fluorouracil aqueous solutions (50 mg/mL) were used. Samples adjusted to six pH levels were examined for precipitate. Drug reservoirs of four different portable infusion pumps were filled with 70 mL of each fluorouracil injection. Under conditions simulating actual use, the reservoirs were attached to the pumps and the solutions were pumped at a rate of 10 mL/24 hours over a seven-day period at 25 degrees C and 37 degrees C. Samples at the distal end of the extension tubing were collected hourly for the first 10 hours and at 12-hour intervals thereafter. Visual observations and pH determinations were made immediately. Drug concentrations were determined by reverse-phase high-performance liquid chromatography. Diethylhexylphthalate (DEHP) concentrations (the result of leaching from the plastic tubing and container) were determined by gas chromatography. In the pH study, precipitate appeared immediately in all fluorouracil injections below pH 8.52; precipitate was observed after two to four hours at pH 8.60-8.68. Under simulated infusion conditions, no apparent changes in concentration or pH were detected with any of the brands of drugs or portable infusion devices. At 25 degrees C, a fine white precipitate was observed in the extension tubing of all devices with the Roche brand of fluorouracil 48 to 96 hours after the pumping cycle began. The amount of DEHP leached from the drug reservoirs over the seven-day period was less than 1 ppm at both temperatures. All tested brands of fluorouracil injection were found to be stable under simulated infusion conditions over a seven-day period at 37 degrees C.