Phonophoresis versus ultrasound in the treatment of common musculoskeletal conditions

PURPOSE: The purpose of this study was to determine whether the pain response after phonophoresis (PH) differs from the pain response after ultrasound (US) alone. METHODS: Forty-nine subjects with soft tissue injuries including epicondylitis, tendinitis, and tenosynovitis were randomly assigned (double blinded technique) to PH or US treatment groups. Both groups received 8 min of continuous US at 1.5 w x cm(-2), three times per week for 3 wk. For the PH group a gel containing 0.05% fluocinonide was used as a coupling agent. An identical gel absent the steroid was used for the US group. Subjects indicated their pain level by marking on a visual analog scale (VAS) at the start of treatment and at the end of weeks 1, 2, and 3. Pressure algometry was used to note tolerance to direct pressure over the target tissue. ANOVA for repeated measures was used to analyze data. RESULTS: At the end of 3 wk of treatment, both groups combined showed a significant decrease in pain level and an increase in pressure tolerance (P < 0.05), but there were no differences between groups from the onset of treatment to the end of week 3 (VAS: US 5.5-1.9, PH 5.0-2.0; algometry (involved limb): US 4.7 lb-7.1 lb, PH 5.1 lb-6.6 lb). CONCLUSIONS: We conclude that US results in decreased pain and increased pressure tolerance in these selected soft tissue injuries. The addition of PH with fluocinonide does not augment the benefits of US used alone.     

Characterization of Werner syndrome protein DNA helicase activity: directionality, substrate dependence and stimulation by replication protein A

Werner syndrome is an inherited disease characterized by premature aging, genetic instability and a high incidence of cancer. The wild type Werner syndrome protein (WRN) has been demonstrated to exhibit DNA helicase activity in vitro. Here we report further biochemical characterization of the WRN helicase. The enzyme unwinds double-stranded DNA, translocating 3'-->5' on the enzyme-bound strand. Hydrolysis of dATP or ATP, and to a lesser extent hydrolysis of dCTP or CTP, supports WRN-catalyzed strand-displacement. K m values for ATP and dATP are 51 and 119 microM, respectively, and 2.1 and 3.9 mM for CTP and dCTP, respectively. Strand-displacement activity of WRN is stimulated by single-stranded DNA-binding proteins (SSBs). Among the SSBs from Escherichia coli, bacteriophage T4 and human, stimulation by human SSB (human replication protein A, hRPA) is the most extensive and occurs with a stoichiometry which suggests direct interaction with WRN. A deficit in the interaction of WRN with hRPA may be associated with deletion mutations that occur at elevated frequency in Werner syndrome cells.     

Proton T1rho-dispersion imaging of rodent brain at 1.9 T

Detection of H2(17)O with proton T1rho-dispersion imaging holds promise as a means of quantifying metabolism and blood flow with MRI. However, this technique requires a priori knowledge of the intrinsic T1rho dispersion of tissue. To investigate these properties, we implemented a T1rho imaging sequence on a 1.9-T Signa GE scanner. A series of T1rho images for different locking frequencies and locking durations were obtained from rat brain in vivo and compared with 5% (wt/vol) gelatin phantoms containing different concentrations of (17)O ranging from .037% (natural abundance) to 2.0 atom%. Results revealed that, although there is considerable T1rho-dispersion in phantoms doped with H2(17)O, the T1rho of rat brain undergoes minimal dispersion for spin-locking frequencies between .2 and 1.5 kHz. A small degree of T1rho dispersion is present below .2 kHz, which we postulate arises from natural-abundance H2(17)O. Moreover, the signal-to-noise ratios of T1rho-weighted images are significantly better than comparable T2-weighted images, allowing for improved visualization of tissue contrast. We have also demonstrated the feasibility of proton T1rho-dispersion imaging for detecting intravenous H2(17)O on a live mouse brain. The potential application of this technique to study brain perfusion is discussed.     

Estimating African American admixture proportions by use of population-specific alleles

We analyzed the European genetic contribution to 10 populations of African descent in the United States (Maywood, Illinois; Detroit; New York; Philadelphia; Pittsburgh; Baltimore; Charleston, South Carolina; New Orleans; and Houston) and in Jamaica, using nine autosomal DNA markers. These markers either are population-specific or show frequency differences >45% between the parental populations and are thus especially informative for admixture. European genetic ancestry ranged from 6.8% (Jamaica) to 22.5% (New Orleans). The unique utility of these markers is reflected in the low variance associated with these admixture estimates (SEM 1.3%-2.7%). We also estimated the male and female European contribution to African Americans, on the basis of informative mtDNA (haplogroups H and L) and Y Alu polymorphic markers. Results indicate a sex-biased gene flow from Europeans, the male contribution being substantially greater than the female contribution. mtDNA haplogroups analysis shows no evidence of a significant maternal Amerindian contribution to any of the 10 populations. We detected significant nonrandom association between two markers located 22 cM apart (FY-null and AT3), most likely due to admixture linkage disequilibrium created in the interbreeding of the two parental populations. The strength of this association and the substantial genetic distance between FY and AT3 emphasize the importance of admixed populations as a useful resource for mapping traits with different prevalence in two parental populations.     

Hyaluronic acid treatment (viscosupplementation) for OA of the knee

Viscosupplementation may be useful in the treatment of OA of the knee when other medical forms of therapy are contraindicated, toxic, or have failed. It may have a role in managing the patient with moderate to severe OA of the knee before considering total knee arthroplasty (Table 2). Viscosupplementation or medical treatment does not replace the need for thigh muscle strengthening or for overweight patients to lose weight. Whether or not efficacy will demand or warrant earlier or repeated use of hyaluronic acid-like products remains to be seen.     

Adenovirus-mediated gene transfer to nucleus pulposus cells. Implications for the treatment of intervertebral disc degeneration

STUDY DESIGN: In vitro and in vivo studies using a rabbit model were performed to determine the feasibility of adenovirus-mediated gene transfer to the intervertebral disc. OBJECTIVES: This study was conducted to determine whether it is possible to transfer genes to cells within the intervertebral disc by direct injection of an adenovirus and to determine the duration of gene expression obtained by this method. SUMMARY OF BACKGROUND DATA: Although growth factors have the potential to stimulate the regeneration of nucleus pulposus, sustained delivery of growth factors to a degenerated disc is clinically unfeasible with present technology. Novel approaches such as gene transfer should be investigated as possible solutions to this problem. METHODS: The lacZ marker gene was used to evaluate gene delivery to cells within intervertebral discs. For the in vitro study, cell cultures were established from the nucleus pulposus tissue of New Zealand white rabbits and infected with an adenovirus encoding the lacZ gene (Ad-lacZ). For the in vivo study, the anterior aspects of lumbar intervertebral discs were surgically exposed, and Ad-lacZ in saline solution was directly injected into the nucleus pulposus. An equal volume of saline only was injected into control discs. Expression of the transferred gene was detected by staining with 5-bromo-4-chloro-3-indolyl-beta-galactosidase (X-Gal). RESULTS: The in vitro experiments confirmed that nucleus pulposus cells were efficiently transduced by an adenoviral vector carrying the lacZ gene. In vivo injection of Ad-lacZ into the nucleus pulposus resulted in the transduction of a considerable number of cells. Marker gene expression in vivo persisted at an apparently undiminished level for at least 12 weeks. No staining was noted in control discs. CONCLUSIONS: The results show the feasibility of adenovirus-mediated gene transfer to the intervertebral disc. Expression of the marker gene persisted at least 12 weeks in vivo. This successful demonstration of exogenous gene transfer to the disc and sustained, long-term expression suggests that the adenoviral vector may be suitable for delivery of appropriate genes to the disc for the treatment of spinal disorders.     

High-speed separation of linear and supercoiled DNA by capillary electrophoresis. Buffer, entangling polymer, and electric field effects

Capillary electrophoresis in dilute and semidilute (slightly entangled) hydroxyethyl cellulose (HEC) is shown to separate linear double-stranded DNA (ds-DNA) and supercoiled plasmid DNA in the size range 1-16 thousand base pairs in 3 min. The mobilities of linear ds-DNA fragments are stronger functions of electric field strength and buffer concentration than the mobilities of supercoiled plasmids. The effects of HEC concentration and molecular weight are similar for both forms of DNA. The behavioral differences, which are attributed to the greater stiffness of the plasmids, can be used to define conditions that maximize resolution of supercoiled and linear ds-DNA of the same or similar number of base pairs.     

Transduction of human trophoblastic cells by replication-deficient recombinant viral vectors. Promoting cellular differentiation affects virus entry

We investigated the transfer of the lacZ reporter gene into human trophoblastic cells using herpes simplex virus and adeno-associated virus vectors. We used an established choriocarcinoma cell line (BeWo cells) that can be induced to terminally differentiate after treatment with cyclic-AMP. Our results demonstrate that transduction of trophoblastic cells by the herpes simplex virus vector, HSV.CMVlac, and the adeno-associated virus vector, AAV.CMVlac, is affected by cellular differentiation. Treatment of BeWo cells with cyclic-AMP reduced transduction by HSV.CMVlac but increased transduction by the AAV vector. In contrast, when BeWo cells were transfected with herpes simplex virus and adeno-associated virus plasmids, lacZ expression was not affected by treatment with cyclic-AMP. Southern blot analysis demonstrated 2.75 times less herpes simplex virus DNA in cyclic-AMP treated BeWo cells, but 2.0 to 7.4 times more adeno-associated virus DNA in treated cells. We conclude that inefficient transduction of differentiated trophoblastic cells with HSV.CMVlac is because of diminished viral entry, whereas cellular differentiation is associated with increased entry of AAV.CMVlac. These observations suggest that adeno-associated virus vectors may be used to modify trophoblast function and study placental physiology. Additionally, trophoblast differentiation leads to alterations in the mechanisms of virus uptake that may affect maternal-to-fetus transmission.     

Macrophage and microglia-like cells in the avian inner ear

Recent studies suggest that macrophages may influence early stages of the process of hair cell regeneration in lateral line neuromasts; numbers of macrophages were observed to increase prior to increases in hair cell progenitor proliferation, and macrophages have the potential to secrete mitogenic growth factors. We examined whether increases in the number of leukocytes present in the in vivo avian inner ear precede the proliferation of hair cell precursors following aminoglycoside insult. Bromodeoxyuridine (BrdU) immunohistochemistry was used to identify proliferating cells in chicken auditory and vestibular sensory receptor epithelia. LT40, an antibody to the avian homologue of common leukocyte antigen CD45, was used to label leukocytes within the receptor epithelia. Macrophages and, surprisingly, microglia-like cells are present in normal auditory and vestibular sensory epithelia. After hair cell loss caused by treatment with aminoglycosides, numbers of macrophage and microglia-like cells increase in the sensory epithelium. The increase in macrophage and microglia-like cell numbers precedes a significant increase in sensory epithelial cell proliferation. The results suggest that macrophage and microglia-like cells may play a role in releasing early signals for cell cycle progression in damaged inner ear sensory epithelium.     

Valproate reduces intake of alcoholic beverage among rats

SETTING: University of Malaya Medical Centre, Kuala Lumpur, Malaysia. OBJECTIVE: To assess the awareness of the ozone layer and the acceptance of the new non-chlorofluorocarbon (CFC) propellant hydrofluoroalkane 134a salbutamol pressurised metered dose inhaler (MDI) Airomir among asthmatic patients. DESIGN: A total of 113 consecutive asthmatic patients aged 12 years and above from the out- and in-patient services of the hospital were interviewed using a questionnaire. RESULTS: Sixty-five per cent of the patients were aware of the existence of the ozone layer, 23% that CFCs play a role in ozone depletion, and only 10% that current MDIs contained CFCs. All the patients felt that pressurised MDIs should be made CFC-free after they had considered the role of CFCs in the destruction of the ozone layer. Eighty-one per cent of 94 patients who preferred the Airomir inhaler over a multi-dose dry powder inhaler for administering bronchodilator medications were willing to switch to the new inhaler once it became available on the market. CONCLUSION: Awareness of the damaging effect of CFCs on the ozone layer among asthmatic patients would encourage them to change to an ozone-friendly, CFC-free pressurised MDI.