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K McCormack

Publications and source records attributed to K McCormack.

At least 19 recordsLinked to original sources
PubMed2006

Maternal care patterns and behavioral development of rhesus macaque abused infants in the first 6 months of life.

We investigated the maternal care patterns of rhesus macaque mothers who physically abuse their infants, and compared their infants' behavior to that of nonabused infants. Parametric and multidimensional scaling analyses indicated that abusive mothers have a distinct parenting style characterized by high rates of rejection and contact-breaking from their infants. Compared to control infants, abused infants exhibited signs of delayed independence from their mothers including higher rates of distress calls and anxiety, lower rates of contact-breaking, and differences in play. Several aspects of the abused infants' behavior were correlated with rates of abuse received during the first month, or with other maternal behaviors. These findings provide a more comprehensive characterization of the parenting styles of abusive mothers and the early behavioral development of their infants than previously available. Detailed knowledge of the early experience of abused infants is crucial for understanding possible pathological alterations in behavior and neuroendocrine function later in life.

Aggression↗
PubMed2005

Transabdominal pre-peritoneal (TAPP) versus totally extraperitoneal (TEP) laparoscopic techniques for inguinal hernia repair: a systematic review.

BACKGROUND: The choice of approach to the laparoscopic repair of inguinal hernia is controversial. There is a scarcity of data comparing the laparoscopic transabdominal preperitoneal (TAPP) approach with the laparoscopic totally extraperitoneal (TEP) approach, and questions remain about their relative merits and risks. METHODS: Electronic databases were searched to identify reports of trials comparing laparoscopic TAPP with laparoscopic TEP. In addition, selected conference proceedings were hand-searched, websites consulted, reference lists of all included papers were scanned, and experts contacted for other potentially eligible reports. All published and unpublished randomised controlled trials and quasi-randomised controlled trials comparing laparoscopic TAPP with laparoscopic TEP for inguinal hernia repair were eligible for inclusion. Large non-randomised prospective studies were also eligible for inclusion to provide further comparative evidence of complications and serious adverse events. Two reviewers independently extracted data and assessed study quality. Statistical analyses were performed using the fixed effects model and the results expressed as relative risk (RR) for dichotomous outcomes and weighted mean difference (WMD) for continuous outcomes with 95% confidence intervals (CI). RESULTS: The search identified one RCT which reported no statistically significant difference between TAPP and TEP when considering duration of operation, haematoma, length of stay, time to return to usual activities, and recurrence. The eight non-randomised studies suggest that TAPP is associated with higher rates of port-site hernias and visceral injuries whilst there appear to be more conversions with TEP. Vascular injuries and deep/mesh infections were rare and there was no obvious difference between the groups. No studies reporting economic evidence were identified. CONCLUSIONS: There is insufficient data to allow conclusions to be drawn about the relative effectiveness of TEP compared with TAPP. Efforts should be made to start and complete adequately-powered randomised controlled trials (RCTs), which compare the different methods of laparoscopic repair.

Female↗
PubMed2005

Transabdominal pre-peritoneal (TAPP) vs totally extraperitoneal (TEP) laparoscopic techniques for inguinal hernia repair.

BACKGROUND: The choice of approach to the laparoscopic repair of inguinal hernia is controversial. There is a scarcity of data comparing the laparoscopic transabdominal preperitoneal (TAPP) approach with the laparoscopic totally extraperitoneal (TEP) approach and questions remain about their relative merits and risks. OBJECTIVES: To compare the clinical effectiveness and relative efficiency of laparoscopic TAPP and laparoscopic TEP for inguinal hernia repair. SEARCH STRATEGY: We searched Medline Extra, Embase, Biosis, Science Citation Index, Cochrane Central Register of Controlled Trials (CENTRAL), Journals@ Ovid Full Text and the electronic version of the journal, Surgical Endoscopy. Recent conference proceedings by the following organisations were hand searched: Association of Endoscopic Surgeons of Great Britain & Ireland; International Congress of the European Association for Endoscopic Surgery; Scientific Session of the Society of American Gastrointestinal & Endoscopic Surgeons (SAGES); and the Italian Society of Endoscopic Surgery. In addition, specialists involved in research on the repair of inguinal hernia were contacted to ask for information about any further completed and ongoing trials, relevant websites were searched and reference lists of the all included studies were checked for additional reports. SELECTION CRITERIA: All published and unpublished randomised controlled trials and quasi-randomised controlled trials comparing laparoscopic TAPP with laparoscopic TEP for inguinal hernia repair were eligible for inclusion. Non-randomised prospective studies were also eligible for inclusion to provide further comparative evidence of complications and adverse events. DATA COLLECTION AND ANALYSIS: Statistical analyses were performed using the fixed effects model and the results expressed as relative risk (RR) for dichotomous outcomes and weighted mean difference (WMD) for continuous outcomes with 95% confidence intervals (CI). MAIN RESULTS: The search identified one RCT which reported no statistical difference between TAPP and TEP when considering duration of operation, haematoma, length of stay, time to return to usual activity and recurrence. The eight non-randomised studies suggest that TAPP is associated with higher rates of port-site hernias and visceral injuries whilst there appear to be more conversions with TEP. Vascular injuries and deep/mesh infections were rare and there was no obvious difference between the groups. No studies reporting economic evidence were identified. Very limited data were available on learning effects but these data suggest that operators become experienced at between 30 and 100 procedures. AUTHORS' CONCLUSIONS: There is insufficient data to allow conclusions to be drawn about the relative effectiveness of TEP compared with TAPP. Efforts should be made to start and complete adequately powered RCTs, which compare the different methods of laparoscopic repair.

Hernia, Inguinal↗
PubMed2005

Genetic modifiers of the Kv beta2-null phenotype in mice.

Shaker-type potassium (K+) channels are composed of pore-forming alpha subunits associated with cytoplasmic beta subunits. Kv beta2 is the predominant Kv beta subunit in the mammalian nervous system, but its functions in vivo are not clear. Kv beta2-null mice have been previously characterized in our laboratory as having reduced lifespans, cold swim-induced tremors and occasional seizures, but no apparent defect in Kv alpha-subunit trafficking. To test whether strain differences might influence the severity of this phenotype, we analyzed Kv beta2-null mice in different strain backgrounds: 129/SvEv (129), C57BL/6J (B6) and two mixed B6/129 backgrounds. We found that strain differences significantly affected survival, body weight and thermoregulation in Kv beta2-null mice. B6 nulls had a more severe phenotype than 129 nulls in these measures; this dramatic difference did not reflect alterations in seizure thresholds but may relate to strain differences we observed in cerebellar Kv1.2 expression. To specifically test whether Kv beta1 is a genetic modifier of the Kv beta2-null phenotype, we generated Kv beta1.1-deficient mice by gene targeting and bred them to Kv beta2-null mice. Kv beta1.1/Kv beta2 double knockouts had significantly increased mortality compared with either single knockout but still maintained surface expression of Kv1.2, indicating that trafficking of this alpha subunit does not require either Kv beta subunit. Our results suggest that genetic differences between 129/SvEv and C57Bl/6J are key determinants of the severity of defects seen in Kv beta2-null mice and that Kv beta1.1 is a specific although not strain-dependent modifier.

Animals↗
PubMed2005

Laparoscopic surgery for inguinal hernia repair: systematic review of effectiveness and economic evaluation.

OBJECTIVES: To determine whether laparoscopic methods are more effective and cost-effective than open mesh methods of inguinal hernia repair, and then whether laparoscopic transabdominal preperitoneal (TAPP) repair is more effective and cost-effective than laparoscopic totally extraperitoneal (TEP). DATA SOURCES: Electronic databases. Conference proceedings. Manufacturers' submissions to the National Institute for Clinical Excellence (NICE) were reviewed. REVIEW METHODS: Selected studies were rigorously assessed. Dichotomous outcome data were combined using the relative risk method and continuous outcomes were combined using the Mantel-Haenszel weighted mean difference method. Time to return to usual activities was described using hazard ratios derived from individual patient data reanalysis. A review of economic evaluations undertaken by NICE in 2001 was updated and an economic evaluation was performed. The estimation of cost-effectiveness focused on the comparison of laparoscopic repair with open flat mesh. A Markov model incorporating the data from the systematic review was used to estimate cost-effectiveness for a time horizon up to 25 years. RESULTS: Thirty-seven randomised control trials (RCTs) and quasi-RCTs met the inclusion criteria on effectiveness. Fourteen studies were included in the review of economic evaluations. Laparoscopic repair was associated with a faster return to usual activities and less persisting pain and numbness. There also appeared to be fewer cases of wound/superficial infection and haematoma. However, operation times are longer and there appears to be a higher rate of serious complications in respect of visceral (especially bladder) injuries. Mesh infection is very uncommon with similar rates noted between the surgical approaches. There is no apparent difference in the rate of hernia recurrence. Laparoscopic repair was more costly to the health service than open repair, with an estimated extra cost from studies conducted in the UK of about 300-350 pounds per patient. The point estimates of cost provided by the economic model also suggest that the laparoscopic techniques are more costly (approximately 100-200 pounds more per patient after 5 years). From the review of economic evaluations, the estimates of incremental cost per additional day at usual activities were between 86 pounds and 130 pounds. Where productivity costs were included, they eliminated the cost differential between laparoscopic and open repair. Additional analysis incorporating new trial evidence suggested that TEP was associated with significantly more recurrences than open mesh but these data did not greatly influence cost-effectiveness. CONCLUSIONS: For the management of unilateral hernias, the base-case analysis and most of the sensitivity analysis suggest that open flat mesh is the least costly option but provides less quality adjusted life years (QALYs) than TEP or TAPP. TEP is likely to dominate TAPP (on average TEP is estimated to be less costly and more effective). It is likely that, for management of symptomatic bilateral hernias, laparoscopic repair would be more cost-effective as differences in operation time (a key cost driver) may be reduced and differences in convalescence time are more marked (hence QALYs will increase) for laparoscopic compared with open mesh repair. When possible repair of contralateral occult hernias is taken into account, TEP repair is most likely to be considered cost-effective at threshold values for the cost per additional QALY above 20,000 pounds. The increased adoption of laparoscopic techniques may allow patients to return to usual activities faster. This may, for some people, reduce any loss of income. For the NHS, increased use of laparoscopic repair would lead to an increased requirement for training and the risk of serious complications may be higher. Chronic pain should now be addressed prospectively using standard definitions and allowing assessment of the degree of pain. More evidence is required on the loss of utility caused by persisting pain and numbness, as well as serious complications resulting from minor surgery. Prospective population-based registries of new surgical procedures may be the best way to address this, as a complement to randomised trials assessing effectiveness. Further research relating to whether the balance of advantages and disadvantages changes when hernias are recurrent or bilateral is also required as current data are limited. Methodologically sound RCTs are needed to consider the relative merits and risks of TAPP and TEP. Further methodological research is required into the complexity of laparoscopic groin hernia repair and the improvement of performance that accompanies experience.

Cost-Benefit Analysis↗
PubMed2004

Value of updating a systematic review in surgery using individual patient data.

BACKGROUND: Previous research has highlighted the advantages of individual patient data (IPD) meta-analyses. However, they are resource intensive and take considerable time to complete. The aim of this study was to determine whether the extra investment is justified by greater accuracy or usefulness by means of a case study in surgery. METHODS: An updated review using IPD, where possible, was compared with an earlier version based on aggregate published data to determine whether there were statistically significant changes in estimates of effectiveness for hernia recurrence and persisting pain. Differences related to the type of laparoscopic repair, the type of open repair and methodological quality were also explored. RESULTS: The results for hernia recurrence changed little. However, the IPD update led to divergent conclusions for persisting pain. The published data implied a statistically significant benefit in favour of open repair, whereas the IPD result implied a statistically significant benefit in favour of laparoscopic repair (P < 0.001). Methodological quality did not account for this difference. CONCLUSION: Updating of systematic reviews using IPD can be conducted successfully in surgery. This example led to little change in estimates of effectiveness for hernia recurrence but yielded qualitatively different estimates for persisting pain, an outcome rarely included in the published reports.

Humans↗
PubMed2003

Laparoscopic techniques versus open techniques for inguinal hernia repair.

BACKGROUND: Inguinal hernia repair is the most frequently performed operation in general surgery. The standard method for inguinal hernia repair had changed little over a hundred years until the introduction of synthetic mesh. This mesh can be placed by either using an open approach or by using a minimal access laparoscopic technique. Although many studies have explored the relative merits and potential risks of laparoscopic surgery for the repair of inguinal hernia, most individual trials have been too small to show clear benefits of one type of surgical repair over another. OBJECTIVES: The objective of this review was to compare minimal access laparoscopic mesh techniques with open techniques. Comparisons of open mesh techniques versus open non-mesh techniques have been considered in a separate Cochrane review. SEARCH STRATEGY: We searched MEDLINE, EMBASE, and The Cochrane Central Controlled Trials Registry for relevant randomised controlled trials. The reference list of identified trials, journal supplements, relevant book chapters and conference proceedings were searched for further relevant trials. Through the EU Hernia Trialists Collaboration (EUHTC) communication took place with authors of identified randomised controlled trials to ask for information on any other recent and ongoing trials known to them. Specialists involved in research on the repair of inguinal hernia were contacted to ask for information about any further completed and ongoing trials. The world wide web was also searched. SELECTION CRITERIA: All published and unpublished randomised controlled trials and quasi-randomised controlled trials comparing laparoscopic groin hernia repair with open groin hernia repair were eligible for inclusion. Trials were included irrespective of the language in which they were reported. DATA COLLECTION AND ANALYSIS: Individual patient data were obtained, where possible, from the responsible trialist for all eligible studies. All reanalyses were cross-checked by the reviewers and verified by the trialists before inclusion. Where IPD were unavailable additional aggregate data were sought from trialists and published aggregate data checked and verified by the trialists. IPD were available for 25 trials, additional aggregated data for seven and published data only for nine. Where possible, time to event analysis for hernia recurrence and return to usual activities were performed on an intention to treat principle. The main analyses were based on all trials. Sensitivity analyses based on the data source and trial quality were also performed. Pre-defined subgroup analyses based on recurrent hernias, bilateral hernias and femoral hernias were also carried out. MAIN RESULTS: 41 published reports of eligible trials were included involving 7161 participants. Sample sizes ranged from 38 to 994, with follow-up from 6 weeks to 36 months. Duration of operation was longer in the laparoscopic groups (WMD 14.81 minutes, 95% CI 13.98 to 15.64; p<0001). Operative complications were uncommon for both methods but more frequent in the laparoscopic group for visceral (Overall 8/2315 versus 1/2599) and vascular (Overall 7/2498 versus 5/2758) injuries. Length of hospital stay did not differ between groups (WMD -0.04 days, 95% CI -0.08 to 0.00; p=0.05, but return to usual activity was earlier for laparoscopic groups (HR 0.56, 95%CI 0.51 to 0.61; p<0.0001 - equivalent to 7 days). The data available showed less persisting pain (Overall 290/2101 versus 459/2399; Peto OR 0.54, 95% CI 0.46 to 0.64; p<0.0001), and less persisting numbness (Overall 102/1419 versus 217/1624; Peto OR 0.38, 95% CI 0.4286 to 0.49; p<0.0001) in the laparoscopic groups. In total, 86 recurrences were reported amongst 3138 allocated laparoscopic repair and 109 amongst 3504 allocated to open repair (Peto OR 0.81, 95% CI 0.61 to 1.08; p = 0.16). The use of mesh during laparoscopic hernia repair is associated with a reduction in the risk of hernia recurrence, significantly so for the transabdominal preperitoneal repair (TAPP) versus open non-mesh repair (overall 26/1440 versus preperitoneal repair (TAPP) versus open non-mesh repair (overall 26/1440 versus 47/1119; Peto OR 0.45, 95% CI 0.28 to 0.72; p=0.0009). However, no difference was detected when comparing laparoscopic methods with open mesh methods of hernia repair. REVIEWER'S CONCLUSIONS: The use of mesh during laparoscopic hernia repair is associated with a relative reduction in the risk of hernia recurrence of around 30-50%. However, there is no apparent difference in recurrence between laparoscopic and open mesh methods of hernia repair. The data suggests less persisting pain and numbness following laparoscopic repair. Return to usual activities is faster. However, operation times are longer and there appears to be a higher risk of serious complication rate in respect of visceral (especially bladder) and vascular injuries.

Hernia, Inguinal↗
PubMed2003

Metal on metal hip resurfacing arthroplasty. An economic analysis.

This paper explores the cost utility of metal-on-metal hip resurfacing arthroplasty (MOM) as an alternative intervention to total hip replacement or 'watchful waiting' for patients with advanced hip disease. Early implant failure among younger and more active elderly patients can mean that the use of total hip replacement (THR) is delayed, with patients managed through 'watchful waiting', a combination of pain control and other non-surgical interventions. Information on costs is combined with evidence on effectiveness from a systematic review in a Markov model in order to estimate the incremental cost per quality adjusted life year (QALY) of MOM relative to THR and 'watchful waiting'.

Journal Article↗
PubMed2003

Systematic review of the clinical effectiveness and cost-effectiveness of tension-free vaginal tape for treatment of urinary stress incontinence.

OBJECTIVES: To evaluate the effectiveness and cost-effectiveness of tension-free vaginal tape (TVT) in comparison with the standard surgical interventions currently used. DATA SOURCES: Literature searches were carried out on electronic databases and websites for data covering the period 1966--2002. Other sources included references lists of relevant articles; selected experts in the field; abstracts of a limited number of conference proceedings titles; and the Internet. REVIEW METHODS: A systematic review of studies including comparisons of TVT with any of the comparators was conducted. Alternative treatments considered were abdominal retropubic colposuspension (including both open and laparoscopic colposuspension), traditional suburethral sling procedures and injectable agents (periurethral bulking agents). The identified studies were critically appraised and their results summarised. A Markov model comparing TVT with the comparators was developed using the results of the review of effectiveness and data on resource use and costs from previously conducted studies. The Markov model was used to estimate costs and quality-adjusted life-years for up to 10 years following surgery and it incorporated a probabilistic analysis and also sensitivity analysis around key assumptions of the model. RESULTS: Based on limited data from direct comparisons with TVT and from systematic reviews, laparoscopic colposuspension and traditional slings have broadly similar cure rates to TVT and open colposuspension, whereas injectable agents appear to have lower cure rates. TVT is less invasive than colposuspension and traditional sling procedures, and is also usually performed under regional or local anaesthesia. The principal operative complication is bladder perforation. There are currently no randomised controlled trial (RCT) data beyond 2 years post-surgery, and long-term effects are therefore currently not known reliably. TVT was more likely to be considered cost-effective compared with the other surgical procedures. Increasing the absolute probability of cure following TVT reduced the likelihood that TVT would be considered cost-effective. CONCLUSIONS: The long-term performance of TVT in terms of both continence and unanticipated adverse effects is not known reliably at the moment. Despite relatively few robust comparative data, it appears that in the short to medium term TVT's effectiveness approaches that of alternative procedures currently available, and is of lower cost. As TVT is a less invasive procedure, it is possible that some women who would currently be managed non-surgically will be considered eligible for TVT. Increased adoption of TVT will require additional surgeons proficient in the technique. It is likely that some of the higher rates of complications, e.g. bladder perforation, reported for TVT are associated with a 'learning curve'. Appropriate training will therefore be needed for surgeons new to the operation, in respect of both the technical aspects of the procedure and the choice of women suitable for the operation. Further research suggestions include unbiased assessments of longer term performance from follow-up of controlled trials or population-based registries; more data from methodologically sound RCTs using standard outcome measures; a surveillance system to detect longer term complications, if any, associated with the use of tape; and rigorous evaluation before extending the use of TVT to women who are currently managed non-surgically.

Colposcopy↗
PubMed2002

Open mesh versus non-mesh for repair of femoral and inguinal hernia.

BACKGROUND: Inguinal hernia repair is the most frequent operation in general surgery. Until recently the standard procedure has been open musculo-aponeurotic repair using sutures under tension to close the defect but 'tension-free' repair using prosthetic mesh is becoming increasingly common in many countries. OBJECTIVES: The purpose of this review is to evaluate open mesh techniques in comparison with open non-mesh techniques for the surgical repair of groin hernia. SEARCH STRATEGY: Electronic databases were searched and further trials were sought from the reference lists of reports of known trials. Through the EU Hernia Trialists Collaboration authors of identified randomised controlled trials were asked for information on any other trials known to them. There was no language restriction. SELECTION CRITERIA: Studies were eligible for inclusion if they were randomised or quasi-randomised trials comparing either a) open mesh with open non-mesh repair of groin hernia or b) open flat mesh repair with plug and mesh repair of groin hernia. DATA COLLECTION AND ANALYSIS: For each outcome the results were derived using data from the best available source. The majority of data for this review came from individual patient data (IPD) supplied by the trialists. When these were unavailable data came from additional aggregated information or from published trial reports. All trials were analysed using the 'intention to treat' principle. MAIN RESULTS: Twenty trials comparing open mesh with open non-mesh repair were identified. Open mesh methods, on average, took 7-10 minutes less to perform than Shouldice procedures, but took 1-4 minutes longer than other non-mesh methods. There were no clear differences between mesh and non-mesh groups for haematomas, seromas or wound/superficial infections. Three serious operative complications were reported after open mesh repair and three following non-mesh repair. Overall, those in the mesh groups had a shorter length of hospital stay and quicker return to usual activities, but this pattern was not observed for all trials. There was a suggestion that persisting pain was less frequent after mesh repair than after non-mesh repair but this result was dependent on one trial and data were not available for 11 trials. There was no evidence of a difference between the groups with respect to persisting numbness. Fewer hernia recurrences were reported after mesh repair (Peto OR: 0.37, 95% CI: 0.26 to 0.51). There were too few data to reliably address differential effects for patients with recurrent, bilateral or femoral hernias. Two trials comparing flat mesh with plug and mesh were identified. There was no clear evidence of differences between the groups. REVIEWER'S CONCLUSIONS: There is evidence that the use of open mesh repair is associated with a reduction in the risk of recurrence of between 50% and 75%. Although the trials were heterogeneous there is also some evidence of quicker return to work and of lower rates of persisting pain following mesh repair.

Clinical Trials as Topic↗
PubMed2001

Light therapy for seasonal affective disorder in primary care: randomised controlled trial.

BACKGROUND: Studies of light therapy have not been conducted previously in primary care. AIMS: To evaluate light therapy in primary care. METHOD: Fifty-seven participants with seasonal affective disorder were randomly allocated to 4 weeks of bright white or dim red light. Baseline expectations for treatment were assessed. Outcome was assessed with the Structured Interview Guide for the Hamilton Depression Scale, Seasonal Affective Disorder Version. RESULTS: Both groups showed decreases in symptom scores of more than 40%. There were no differences in proportions of responders in either group, regardless of the remission criteria applied, with around 60% (74% white light, 57% red light) meeting broad criteria for response and 31% (30% white light, 33% red light) meeting strict criteria. There were no differences in treatment expectations. CONCLUSIONS: Primary care patients with seasonal affective disorder improve after light therapy, but bright white light is not associated with greater improvements.

Adolescent↗
PubMed2001

Methodological issues using household budget survey expenditure data for individual food availability estimation: Irish experience in the DAFNE pan-European project. DAta Food NEtworking.

OBJECTIVE: Irish participation in the EU-supported DAta Food NEtworking (DAFNE) project required compliance with the overall aims and objectives. The Irish Household Budget Survey (HBS) expenditure data had to be transformed into a format compatible with the collaborative effort, by converting them into quantities of foodstuffs available per person per day. SETTING: The Irish 1987 HBS expenditure data on all commodities for 7705 households in the Republic of Ireland, collected using a 14-day diary kept by all members of the household aged 15 years and over. DESIGN: Following identification of 188 food items in the HBS dataset, retail prices per unit weight were sought for each food. Adjustment of prices, collected from a number of different sources, was made to those of 1987 using the Consumer Price Index. Simple models were used to estimate household food availability through application of the adjusted retail prices per unit weight to the expenditure data. The household level data were converted to food availability per person per day. An internal validation of quantities estimated using the retail prices was made using the 12 foodstuffs for which the Irish HBS collects expenses and quantities. RESULTS: The comparison of quantities published by the Irish Central Statistics Office for 12 foodstuffs in the Irish 1987 Household Budget Survey with the quantities estimated using equivalent expenditure data and corresponding retail prices showed agreement, with less than a 10% margin of error for 10 of the foods. CONCLUSION: In spite some difficulty in converting HBS food expenditure data into food availability per person per day, the DAFNE approach is potentially useful for Irish nutrition surveillance purposes and for facilitating comparisons of the Irish HBS food data with those of other European countries.

Adolescent↗
PubMed2000

Assay of topically administered ibuprofen using a model of post-injury hypersensitivity. A randomised, double-blind, placebo-controlled study.

OBJECTIVE: To develop a reliable assay for quantifying the analgesic efficacy of non-steroidal anti-inflammatory drugs (NSAIDs) using a model that is accepted as a paradigm of clinical pain. SUBJECTS: Fifteen normal subjects, all of whom were volunteers from medical school staff, took part in the study. METHODS: Capsaicin (20 microl) in solution (0.03 mg/ml) was applied to the volar surface of the forearm, and the skin was maintained at a constant temperature using a thermal stimulator. The magnitude of the surrounding area of mechanical allodynia to a brush stimulus (i.e. a clinical correlate of tenderness to touch) was assessed. Under double-blind, placebo-controlled conditions, the test was repeated using skin previously treated with ibuprofen gel or placebo. RESULTS: A close linear relationship was observed between skin temperature over a range of 30 degrees C to 40 degrees C and the area of capsaicin-induced allodynia. Ibuprofen gel significantly reduced (P < 0.004) the area of touch-evoked allodynia at a constant skin temperature of 40 degrees C. CONCLUSIONS: The thermal-facilitated adaptation of the capsaicin model described in this study represents an inexpensive and reliable assay for the effects of topical formulations of NSAID upon mechanical sensitivity. As such, it is a potential alternative to many clinical studies in which inherent confounding and bias can preclude a meaningful conclusion.

Administration, Topical↗
PubMed1999

The effects of Shaker beta-subunits on the human lymphocyte K+ channel Kv1.3.

The activation of T-lymphocytes is dependent upon, and accompanied by, an increase in voltage-gated K+ conductance. Kv1.3, a Shaker family K+ channel protein, appears to play an essential role in the activation of peripheral human T cells. Although Kv1.3-mediated K+ currents increase markedly during the activation process in mice, and to a lesser degree in humans, Kv1.3 mRNA levels in these organisms do not, indicating post-transcriptional regulation. In other tissues Shaker K+ channel proteins physically associate with cytoplasmic beta-subunits (Kvbeta1-3). Recently it has been shown that Kvbeta1 and Kvbeta2 are expressed in mouse T cells and that they are up-regulated during mitogen-stimulated activation. In this study, we show that the human Kvbeta subunits substantially increase K+ current amplitudes when coexpressed with their Kv1.3 counterpart, and that unlike in mouse, protein levels of human Kvbeta2 remain constant upon activation. Differences in Kvbeta2 expression between mice and humans may explain the differential K+ conductance increases which accompany T-cell proliferation in these organisms.

Animals↗
PubMed1999

Comparative analgesic effects of H-wave therapy and transcutaneous electrical nerve stimulation on pain threshold in humans.

OBJECTIVE: To assess the comparative analgesic efficacy of H-wave therapy (HWT) and transcutaneous electrical nerve stimulation (TENS) using a mechanical model of pain threshold measurement. STUDY DESIGN: Forty-eight healthy human volunteers (24 women, 24 men) were recruited and randomly assigned into one of six experimental groups; control, HWT (placebo, 2Hz, or 60Hz), or TENS (placebo or 110Hz). For each subject, mechanical pain threshold (MPT) measurements were recorded at three standardized recording points marked on the dorsal web space of the dominant hand. Two MPT measurements were recorded at each point at the following time intervals: before treatment was initiated (baseline), after each of three consecutive 10-minute periods of stimulation (HWT or TENS), and at four intervals within 30 minutes after stimulation. In the control and placebo groups MPT measurements were recorded at similar time intervals. RESULTS: Difference scores, calculated from patients' baseline values, were analyzed by ANOVA for each of the three recording points. Although results showed a significant increase in MPT levels in all three stimulation groups when compared with their relative placebo (indicating a hypoalgesic effect), no differences were observed between the different modalities or HWT frequencies. Significant hypoalgesia continued for 5 minutes after stimulation. CONCLUSION: The findings showed that HWT and TENS provided localized hypoalgesia during stimulation and for up to 5 minutes after it. No frequency- or modality-specific effects were observed between the groups.

Adult↗