Meta-analysis of transcutaneous electrical nerve stimulation for relief of spinal pain.

We conducted a systematic review and meta-analysis analysing the existing data on transcutaneous electrical nerve stimulation (TENS) or interferential current (IFC) for chronic low back pain (CLBP) and/or neck pain (CNP) taking into account intensity and timing of stimulation, examining pain, function and disability. Seven electronic databases were searched for TENS or IFC treatment in non-specific CLBP or CNP. Four reviewers independently selected randomized controlled trials (RCTs) of TENS or IFC intervention in adult individuals with non-specific CLBP or CNP. Primary outcomes were for self-reported pain intensity and back-specific disability. Two reviewers performed quality assessment, and two reviewers extracted data using a standardized form. Nine RCTs were selected (eight CLBP; one CNP), and seven studies with complete data sets were included for meta-analysis (655 participants). For CLBP, meta-analysis shows TENS/IFC intervention, independent of time of assessment, was significantly different from placebo/control (p < 0.02). TENS/IFC intervention was better than placebo/control, during therapy (p = 0.02), but not immediately after therapy (p = 0.08), or 1-3 months after therapy (p = 0.99). Analysis for adequate stimulation parameters was not significantly different, and there was no effect on disability. This systematic review provides inconclusive evidence of TENS benefits in low back pain patients because the quality of the studies was low, and adequate parameters and timing of assessment were not uniformly used or reported. Without additional high-quality clinical trials using sufficient sample sizes and adequate parameters and outcome assessments, the outcomes of this review are likely to remain unchanged. SIGNIFICANCE: These data highlight the need for additional high-quality RCTs to examine the effects of TENS in CLBP. Trials should consider intensity of stimulation, timing of outcome assessment and assessment of pain, disability and function.

Clinical outcome of partial cystectomy for transitional cell carcinoma of the canine bladder.

Canine transitional cell carcinoma (TCC) of the bladder has historically been treated with a combination of chemotherapy, cyclooxygenase inhibitors and radiation therapy. While surgery has been used to treat TCC of the bladder, its efficacy has yet to be established. Thirty-seven client owned dogs that underwent partial cystectomy +/- various nonsurgical treatments for TCC were retrospectively evaluated. The overall median progression-free interval (PFI) was 235 days and the median survival time (ST) was 348 days. Prognostic factors identified on univariate analysis significant for ST were age, tumor location, full thickness excision and frequency of piroxicam administration. Prognostic factors significant for PFI were full thickness excision and frequency of piroxicam administration. The median ST with partial cystectomy and daily piroxicam therapy, with or without chemotherapy, was 772 days. Dogs with non-trigonal bladder TCC treated with full thickness partial cystectomy and daily piroxicam (+/- chemotherapy) may have improved outcome compared to dogs treated with medical therapy.

The Flint Animal Cancer Center (FACC) Canine Tumour Cell Line Panel: a resource for veterinary drug discovery, comparative oncology and translational medicine.

Mammalian cell tissue culture has been a critical tool leading to our current understanding of cancer including many aspects of cellular transformation, growth and response to therapies. The current use of large panels of cell lines with associated phenotypic and genotypic information now allows for informatics approaches and in silico screens to rapidly test hypotheses based on simple as well as complex relationships. Current cell line panels with large amounts of associated drug sensitivity and genomics data are comprised of human cancer cell lines (i.e. NCI60 and GDSC). There is increased recognition of the contribution of canine cancer to comparative cancer research as a spontaneous large animal model with application in basic and translational studies. We have assembled a panel of canine cancer cell lines to facilitate studies in canine cancer and report here phenotypic and genotypic data associated with these cells.

Diagnostic accuracy of pre-treatment biopsy for grading soft tissue sarcomas in dogs.

Histologic grade is an important prognostic factor for both local recurrence and metastatic potential with canine soft tissue sarcoma (STS). Pre-treatment biopsy with identification of tumour grade may aid in prognostication and determination of surgical margins necessary for local control. The purpose of this study was to evaluate the grading accuracy of various pre-treatment biopsy techniques (wedge, punch, needle-core) for STS in dogs. Medical records of 68 dogs diagnosed with a STS via pre-treatment biopsy and confirmed by excisional biopsy were evaluated. The concordance in grade between excisional and pre-treatment biopsies was 59%. Of the 41% that lacked concordance, 29% of pre-treatment biopsies underestimated and 12% overestimated grade. The method of pre-treatment biopsy did not significantly effect grade concordance. Based on these data, needle-core biopsy appears to be similar in accuracy compared to open biopsy, however, grading determined by pre-treatment biopsy in general should be interpreted with caution.

Insomnia and the eye of the beholder: are there clinical markers of objective sleep disturbances among adults with and without insomnia complaints?

Previous findings suggest that some who report insomnia sleep well, whereas some noncomplaining individuals sleep rather poorly. This study was conducted to determine if mood, anxiety, and sleep-related beliefs might relate to perceived sleep disturbance. Thirty-two women and 32 men (aged 40-79 years) with primary insomnia and an aged-matched sample of 61 normal sleepers (31 women, 30 men) completed 6 nocturnal sleep recordings, as well as the Beck Depression Inventory (BDI), the Trait portion of the State-Trait Anxiety Inventory (STAI-2), and the Dysfunctional Beliefs and Attitudes About Sleep Questionnaire. Sleep and interview data were used to subdivide the majority of the sample (n = 108) into objective normal sleepers and subjective insomnia sufferers who seemingly slept well and subjective normal sleepers and objective insomnia sufferers who slept poorly. The 2 subjective subgroups showed the most marked differences on most of the psychometric measures. The findings suggest that the psychological factors scrutinized in this study may mediate sleep satisfaction and/or predict objective sleep difficulties.

Understanding and affirming the sexual/relationship realities of end-stage renal disease patients and their significant others.

End-stage renal disease (ESRD) frequently occurs within the social context of relationships and has many predictable consequences in the experience of patients and their significant others. Relationship and sexual issues and concerns must be assessed early in the treatment process and be continually attended to as patients seek new levels of coping. Sex-role conflicts, changes in sexual functioning and sexual self-esteem, challenges to both physical and emotional intimacy, and the life-altering consequences of chronic illness are all very real for ESRD patients. If a holistic perspective on the health care needs of ESRD patients is to be a reality, it will contain a concern for, active attention to, and involvement in the relationship/sexual dimension of life.

Sleep in the laboratory and sleep at home: comparisons of older insomniacs and normal sleepers.

Many laboratory polysomnographic (LPSG) studies have shown only modest sleep differences between insomniacs and matched, noncomplaining normal controls. However, the extent to which LPSG methodology affects the outcome of such comparisons has yet to be tested. In the current investigation, 32 (16 females, 16 males) older (age > or = 60 years) insomniacs and an age-matched and gender-matched sample of 32 noncomplaining normal sleepers underwent three consecutive nights of LPSG monitoring and another three consecutive nights of PSG monitoring in their homes (HPSG). By random assignment, one-half of the subjects in each group underwent LPSG first, whereas the remaining subjects underwent HPSG first. Each PSG recording was blindly scored using conventional scoring criteria, and resulting measures of total sleep period, total sleep time, sleep efficiency percent, stage 1 time, slow-wave sleep time, and rapid eye movement latency were used to compare the two subject groups within each PSG recording site (i.e. lab and home). Statistical analyses showed the normals sleepers and insomniacs evidenced similar pronounced first night effects (FNEs) when undergoing LPSG. However, neither mean values of the selected sleep parameters nor measures reflecting their night-to-night variability differentiated the insomniacs from the normal sleepers when such measures were derived from LPSG. In contrast, FNEs were generally absent for both subject groups when they underwent HPSG. Moreover, the insomniacs displayed significantly greater variability in several of their sleep measures during HPSG than did the normal sleepers. Overall, results suggest FNEs are a concern mainly when using LPSG, and HPSG may be more sensitive than LPSG for documenting sleep differences between normal sleepers and insomniacs. Additional studies are needed to determine if the findings reported herein are similar for young and middle-aged adults.

Do our methods lead to insomniacs' madness?: Daytime testing after laboratory and home-based polysomnographic studies.

Complaints of daytime dysfunction are common among chronic insomniacs, but laboratory comparisons of insomniacs and age-matched and gender-matched normal controls have generally failed to document these complaints. However, a few studies, which allowed subjects to sleep in their homes on the nights before daytime testing, have shown some relative diurnal deficits among insomniacs. The current study compared the effects of nocturnal laboratory and home polysomnogram (PSG) studies on subsequent daytime test results among older insomniacs and normal sleepers. Insomniacs (n = 32) and normal sleepers (n = 32) were randomly assigned to first undergo three nights of nocturnal PSG monitoring either in the sleep laboratory (16 insomniacs, 16 normal sleepers) or in their homes (16 insomniacs, 16 normal sleepers). Following the third night of PSG monitoring, subjects spent 1 day in the sleep laboratory, where they completed a four-trial multiple sleep latency test along with four trials of a computer-administered performance test battery. Results showed that insomniacs, as a group, were slightly, albeit consistently, sleepier than were normal sleepers following nights of home sleep monitoring, but a reverse of this trend was found among subjects who underwent nocturnal laboratory PSG before daytime testing. Furthermore, normal sleepers showed faster reaction times on a signal detection task than did insomniacs within the subgroup who underwent home PSGs prior to such testing. However, within the subgroup that underwent nocturnal laboratory PSGs, insomniacs' signal detection reaction times were significantly faster than those shown by normal sleepers. Results provide some support for the speculation that the nocturnal PSG monitoring site, used as a precursor to daytime testing, may systematically affect daytime comparisons between insomniacs and matched controls. Moreover, these results suggest that the use of home-based nocturnal PSG monitoring prior to daytime testing may provide an enhanced understanding of insomniacs' diurnal complaints.

Comparison of cognitive-behavioral therapy and clonazepam for treating periodic limb movement disorder.

Many patients with periodic limb movement disorder (PLMD) display inadequate sleep hygiene, and others decline conventional pharmacologic intervention for their form of sleep disturbance. Nonetheless, the use of nonpharmacologic therapies with PLMD remains unexplored. The current study was designed to compare the short-term treatment effects of a cognitive-behavioral therapy (CBT) and conventional pharmacotherapy (clonazepam) among a group of insomniacs with PLMD. The 16 subjects participating in this study first underwent baseline assessment procedures, including completion of a sleep log for 2 weeks, an ambulatory polysomnogram (APSG) and an Insomnia Symptom Questionnaire (ISQ). They then were randomized either to CBT (n = 8) or standard clonazepam therapy (n = 8). Subjects maintained sleep logs throughout a 4-week treatment and then completed a second APSG and ISQ. Comparison of pre- and post-treatment data suggested that the two treatments led to equal improvements in sleep log measures of sleep-wake times and ISQ measures of subjective sleep concerns. Patients treated with CBT showed a decrease in daytime napping, whereas the clonazepam group reported increased napping. Conversely, those treated with clonazepam showed larger declines in periodic limb movement-arousals per hour of sleep than did the CBT group. Post-treatment interviews suggested that both CBT and clonazepam therapies were generally well tolerated by study participants. It is concluded that both treatments may be useful for PLMD but that the two treatments may have contrasting effects across selected measures of improvement. Additional research is needed to examine the long-term efficacy of CBT as a primary or adjunctive treatment for varying levels of PLMD severity.

Performance evaluation of a distance learning program.

This paper presents a performance metric which uses a single number to characterize the response time for a non-deterministic client-server application operating over the Internet. When applied to a Macintosh-based distance learning application called the Digital Anatomist Browser, the metric allowed us to observe that "A typical student doing a typical mix of Browser commands on a typical data set will experience the same delay if they use a slow Macintosh on a local network or a fast Macintosh on the other side of the country accessing the data over the Internet." The methodology presented is applicable to other client-server applications that are rapidly appearing on the Internet.

Yeast MCK1 protein kinase autophosphorylates at tyrosine and serine but phosphorylates exogenous substrates at serine and threonine.

The product of the Saccharomyces cerevisiae MCK1 gene is a protein kinase that phosphorylates poly (Glu,Tyr) in vitro and is itself phosphorylated at both tyrosine and serine in vivo. To characterize the substrate specificity of Mck1, the enzyme was purified to apparent homogeneity from the soluble fraction of yeast cell extracts by ammonium sulfate precipitation, followed by ion exchange chromatography (Q- and S-Sepharose), dye-ligand affinity chromatography (Orange A-agarose), adsorption chromatography (hydroxylapatite), and ion exchange fast protein liquid chromatography (Mono-S). In the absence of an exogenous substrate, purified Mck1 was able to autophosphorylate on tyrosine and serine. A catalytically inactive mutant (K68R in conserved kinase domain II) expressed in an mck1 delta strain did not contain detectable phosphotyrosine, confirming that the tyrosine phosphorylation observed in vivo is due to autophosphorylation, but did contain phosphoserine, suggesting that Mck1 is a target for other cellular protein kinases. Purified Mck1 phosphorylated a variety of proteins in heat-inactivated yeast extracts, primarily on serine (and threonine). The purified enzyme also used a number of mammalian proteins as phosphoacceptors, including myelin basic protein (MBP), microtubule-associated protein 2 (MAP-2), and tau protein. All of these substrates were phosphorylated on either serine or threonine (or both). Mck1 isolated from yeast extracts by immunoprecipitation with an anti-Mck1 antibody directed against its C terminus also phosphorylated MBP at serine. In the same immune complex kinase assay, the K68R mutant did not detectably phosphorylate MBP, indicating that the serine-specific phosphotransferase activity of Mck1 is intrinsic and not due to contamination by an associated kinase. These findings demonstrate that Mck1 is a member of a novel class of protein kinases that displays the ability to phosphorylate all three hydroxyamino acids in proteins.

Aerobic fitness, acute exercise and sleep in older men.

In the current study 12 aerobically fit and 12 sedentary older men underwent two nocturnal polysomnographic (PSG) studies. A control PSG was conducted following a day without aerobic activity, whereas a postexercise PSG study was conducted following an afternoon session of exhaustive aerobic exercise. In addition to deriving usual sleep parameters, a computer scoring program was used to count the number of individual electroencephalographic (EEG) slow waves in each PSG tracing. Multivariate and univariate analyses showed that the fit subjects had shorter sleep onset latencies, less wake time after onset, fewer discrete sleep episodes, fewer sleep stage shifts during the initial portion of the night, less stage 1 sleep, a higher sleep efficiency and more total slow waves during both PSGs than did the sedentary subjects. Although no main effects were found for the acute exercise challenge, post hoc analyses showed that high levels of body heating during exercise predicted increased sleep fragmentation for both fit and sedentary subjects. These findings provide initial support for the contention that exercise and fitness may have significant effects on the sleep of older men. However, results also suggest that high levels of body heating resulting from a single exercise challenge may have adverse effects. Implications of the study are discussed and suggestions for future research are provided.

A network model for wide area access to structural information.

Structural information in medicine is information about the physical body. Recent advances in medical imaging and biotechnology have greatly increased the amount and importance of structural information, and advances in networking envisioned by the High Performance Computing and Communication Initiative (HPCC) will allow this kind of information to be delivered to remote clients over wide area networks. One of the most important factors determining the usability of such a client-server configuration is the time delay between the request for information from the server, and its presentation to the user at the client. In this paper we present a model for predicting the performance of a structural information client based on the ping time, a simple, unobtrusive network measurement. Preliminary results suggest that the relationship between ping time and transfer time for large files is linear, which if borne out by more data, will allow the performance of structural information clients at remote sites to be predicted without the expense of installing them first. At the same time, such a model will be useful for planning improvements to the network in those sites which could most benefit by wide area access to structural information.

The phenotypically variable surface protein of Trichomonas vaginalis has a single, tandemly repeated immunodominant epitope.

Trichomonas vaginalis is a sexually transmitted protozoan parasite that undergoes phenotypic variation for numerous surface proteins. A monoclonal antibody (MAb) was used to isolate an approximately 400-bp cDNA encoding a fragment of an important phenotypically varying immunogen of T. vaginalis (Mr = 270 kDa; P270). The MAb completely inhibited the binding of P270 by antibody in sera of patients and by antibody in monospecific antiserum obtained toward purified P270, indicating that P270 contained only one immunodominant epitope. Hydrophilicity plot analysis of the deduced amino acid sequence of the recombinant protein predicted the hexapeptide sequence DREGRD as the antigenic determinant of P270. Synthetic peptides synthesized to this region demonstrated that the amino acid sequence DREGRD is important for antibody binding. Seven adjacent amino acids also contributed substantially to maximal recognition of the epitope by the MAb. A single transcript of approximately 9.5 kb, a size compatible with the reported Mr of the immunogen, hybridized to the cDNA in Northern blots of total RNA from T. vaginalis. DNA sequence and Southern blot analysis determined the epitope to be encoded by a 339-bp unit, which was found to be tandemly repeated at least 12 times within the single-copy gene. This 12-mer unit would only constitute approximately 50% of the protein, yet it is responsible for all of the serum antibody to the immunogen produced by animals and humans. The epitope sequence was found in all fresh and long-term-grown organisms examined to date, demonstrating the stability and conservation of this gene.

Novel yeast protein kinase (YPK1 gene product) is a 40-kilodalton phosphotyrosyl protein associated with protein-tyrosine kinase activity.

Extracts of bakers' yeast (Saccharomyces cerevisiae) contain protein-tyrosine kinase activity that can be detected with a synthetic Glu-Tyr copolymer as substrate (G. Schieven, J. Thorner, and G.S. Martin, Science 231:390-393, 1986). By using this assay in conjunction with ion-exchange and affinity chromatography, a soluble tyrosine kinase activity was purified over 8,000-fold from yeast extracts. The purified activity did not utilize typical substrates for mammalian protein-tyrosine kinases (enolase, casein, and histones). The level of tyrosine kinase activity at all steps of each preparation correlated with the content of a 40-kDa protein (p40). Upon incubation of the most highly purified fractions with Mn-ATP or Mg-ATP, p40 was the only protein phosphorylated on tyrosine. Immunoblotting of purified p40 or total yeast extracts with antiphosphotyrosine antibodies and phosphoamino acid analysis of 32P-labeled yeast proteins fractionated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis indicated that the 40-kDa protein is normally phosphorylated at tyrosine in vivo. 32P-labeled p40 immunoprecipitated from extracts of metabolically labeled cells by affinity-purified anti-p40 antibodies contained both phosphoserine and phosphotyrosine. The gene encoding p40 (YPK1) was cloned from a yeast genomic library by using oligonucleotide probes designed on the basis of the sequence of purified peptides. As deduced from the nucleotide sequence of YPK1, p40 is homologous to known protein kinases, with features that resemble known protein-serine kinases more than known protein-tyrosine kinases. Thus, p40 is a protein kinase which is phosphorylated in vivo and in vitro at both tyrosine and serine residues; it may be a novel type of autophosphorylating tyrosine kinase, a bifunctional (serine/tyrosine-specific) protein kinase, or a serine kinase that is a substrate for an associated tyrosine kinase.

Characterization of Trichomonas vaginalis haemolysis.

The haemolytic activity of live Trichomonas vaginalis organisms was investigated. Optimal haemolysis of human erythrocytes was observed at a parasite to erythrocyte ratio of 1:5 during a 2 h incubation period. No haemolytic activity was detected in concentrated culture supernatants after overnight growth of trichomonads or when parasites were separated from erythrocytes by a 3 microns filter, suggesting a contact-dependent mechanism for haemolysis. The haemolytic activity was temperature-dependent and maximal haemolysis occurred at 37 degrees C. Treatment of trichomonads with metronidazole reduced levels of haemolysis by greater than 50%. Maximal haemolysis occurred at the pH range of the vagina during trichomoniasis. N-alpha-tosyl-L-lysyl-chloromethyl ketone and iodoacetamide, inhibitors of trichomonad cysteine proteinases, reduced the haemolytic activity of live parasites.

Specific erythrocyte binding is an additional nutrient acquisition system for Trichomonas vaginalis.

Specific receptor-mediated binding by Trichomonas vaginalis of human erythrocytes was demonstrated. The ability of live parasites to internalize erythrocytes was also documented. In vitro growth assays during lipid-free and iron-limiting conditions that do not support the survival of T. vaginalis organisms showed that purified erythrocyte lipids and hemoglobin were each able to provide lipids and/or hemoglobin iron for trichomonal growth and multiplication. Parasites bound hemoglobin in a highly specific receptor-mediated fashion, and only the homologous unlabeled hemoglobin, but not lactoferrin and transferrin, competed with iodinated hemoglobin binding. Two antibody-crossreactive surface proteins of the parasites were identified as adhesins, and antibody to the individual adhesins inhibited T. vaginalis recognition and binding of erythrocytes. Finally, patient sera possessed antibody to the adhesins, showing the immunogenic nature and in vivo relevance of the trichomonad proteins during infection.

Dyadic adjustment/sexual satisfaction in women and men as a function of psychological sex role self-perception.

Men and women who were found to be androgynous in the sexual situation were more sexually satisfied and had better adjustment in their dyadic relationship than their sex role stereotypic counterparts. This finding was not surprising, since androgyny implies more flexibility. On the other hand, the finding was surprising in light of the fact that large numbers of both men and women in the study sample perceived themselves as feminine in the sexual situation, compared to their global sex role self-perception. Several explanations are offered with respect to these outcomes, and the importance of qualitative differences between men and women is highlighted.