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Biomedical subjects

M L Kennedy

Publications and source records attributed to M L Kennedy.

At least 19 recordsLinked to original sources
PubMed2007

Sacral nerve stimulation induces pan-colonic propagating pressure waves and increases defecation frequency in patients with slow-transit constipation.

OBJECTIVE: Colonic propagating sequences are important for normal colonic transit and defecation. The frequency of these motor patterns is reduced in slow-transit constipation. Sacral nerve stimulation (SNS) is a useful treatment for fecal and urinary incontinence. A high proportion of these patients have also reported altered bowel function. The effects of SNS on colonic propagating sequences in constipation are unknown. Our aims were to evaluate the effect of SNS on colonic pressure patterns and evaluate its therapeutic potential in severe constipation. METHOD: In eight patients with scintigraphically confirmed slow-transit constipation, a manometry catheter (16 recording sites at 7.5 cm intervals) was positioned colonoscopically and the tip fixed in the caecum. Temporary electrodes (Medtronic) were implanted in the S2 and S3 sacral nerve foramina under general anaesthesia. In the fasted state, 14 Hz stimulation was administered and four sets of parameters (pulse width 300 or 400 micros; S2 and S3) were tested in four 2-h epochs, in random order, over 2 days. Patients were then discharged home with the sacral wires in situ and a 3-week trial stimulation commenced during which patients completed a daily stool diary. RESULTS: When compared with basal activity, electrical stimulation to S3 significantly increased pan-colonic antegrade propagating sequence (PS) frequency (5.4 +/- 4.2 vs 11.3 +/- 6.6 PS/h; P=0.01). Stimulation at S2 significantly increased retrograde PSs (basal 2.6 +/- 1.8 vs SNS 5.6 +/- 4.8 PS/h; P=0.03). During the subsequent three-week trial (continuous stimulation), six of eight reported increased bowel frequency with a reduction in laxative usage. CONCLUSION: These data demonstrate that SNS induces pan-colonic propagating pressure waves and therefore shows promise as a potential therapy for severe refractory constipation.

Adult↗
PubMed2005

The anxiolytic-like effects of Aloysia polystachya (Griseb.) Moldenke (Verbenaceae) in mice.

The aim of the present work is to demonstrate the putative sedative and anxiolytic-like effects of a hydro-ethanolic extract obtained from the aerial parts of Aloysia polystachya (Verbenaceae) in male mice using several behavioural assays. Groups of male mice orally treated with doses of 1.0, 10.0 and 100.0 mg/kg of the extract did not show any significant alteration of their locomotor activity, body temperature or motor coordination. The same treatment increased the duration of the sleeping time induced by 30.0 mg/kg i.p. of sodium pentobarbital. However, the sleeping time induced by ethyl ether was not modified by the oral administration of the extract, not confirming the putative sedative effect of the plant. The ethanolic extract also significantly increased the percentage of both entries (1.0 and 100.0 mg/kg) and the time spent (10.0 and 100.0 mg/kg) into the open arms of the elevated plus maze (EPM). Nevertheless, the binding of (3)H-flunitrazepam ((3)H-FNZ) to the benzodiazepine binding site (BDZ-bs), in washed crude synaptosomal membranes from rat cerebral cortex, was not affected by the semi-purified components from Aloysia polystachya. These results indicate an anxiolytic-like profile of action for the extract of Aloysia polystachya without sedative side effect, being this activity probably mediated by other mechanism than BDZ-bs modulation at the GABA(A) receptors.

Animals↗
PubMed2005

Manometric effect of topical glyceryl trinitrate and its impact on chronic anal fissure healing.

INTRODUCTION: The duration of physiologic action of topical glyceryl trinitrate in the management of anal fissure has been the source of some controversy. This study was designed to assess the manometric effect of glyceryl trinitrate on internal sphincter resting tone with continuous monitoring. METHODS: Twenty-seven patients with a chronic anal fissure were assessed with fissure, pain, bleeding, and continence scores. Twenty-two were randomized to 1 cm of topical 0.2 percent glyceryl trinitrate paste, applied to the lower anal canal. Five patients were randomized to 1 cm of water-soluble lubricating jelly to the lower anal canal. Continuous stationary six radial channel water perfusion anorectal manometry was performed for 5 minutes before treatment and then for a further 30 minutes. The 22 glyceryl trinitrate patients were then advised to apply topical 0.2 percent glyceryl trinitrate, three times daily, for eight weeks. Twenty-four hours after completing treatment, all baseline assessments were repeated. The lubricant jelly cohort was discharged from the study after the initial assessment. RESULTS: During the initial manometric assessment, 21 glyceryl trinitrate patients (95 percent) had 20 percent or more reduction in mean and maximum anal resting pressure after treatment. However, there was no statistical difference at 20 minutes compared with 0 minutes (P > 0.1). After eight-week treatment, 16 patients (73 percent) reported symptom resolution and 15 (67 percent) were found to be healed on examination. Clinical healing and resolution of symptoms positively correlated with a higher pretreatment maximum anal resting pressure in the mid anal canal (P < 0.0001), lower fissure score (P < 0.0001), and greater percentage reduction of the maximum resting pressure after application of glyceryl trinitrate (P < 0.001). The mean and maximum anal resting pressure at Week 8 was not significantly different from the baseline values (P > 0.05). During continuous manometry, the anal resting pressure did not significantly change in the patients treated with lubricating jelly. CONCLUSIONS: In those patients with a lower fissure score, a higher mid anal canal anal resting pressure, and a greater resting pressure reduction after glyceryl trinitrate application, a favorable clinical outcome can be expected with glyceryl trinitrate treatment. However, because the physiologic response has resolved in fewer than 20 minutes, the dosing regime should be reassessed.

Administration, Topical↗
PubMed2005

Prospective manometric assessment of botulinum toxin and its correlation with healing of chronic anal fissure.

INTRODUCTION: The efficacy and pharmacokinetics of botulinum toxin for chronic anal fissure continues to be debated. Addressing both issues we prospectively assessed the manometric impact of botulinum toxin on internal anal sphincter pressure, correlating this impact with chronic anal fissure healing. METHODS: Sixty patients with chronic fissures were assessed. Fifty-seven patients had a total of 20 units of botulinum toxin injected into the intersphincteric groove at four o'clock and eight o'clock. Patients were prospectively assessed with a linear analog pain score, bleeding score, clinical fissure score, modified St. Mark's continence score, and anorectal manometry. Each parameter was reassessed two weeks following treatment and again at three months. RESULTS: Fifty-six patients (30 female), median age 43 (range, 17-80) years, were followed for a median of five (range, 3-15) months with fissure healing assessed 12 weeks after treatment. Physical healing and symptom control were dependent on the baseline maximum anal resting pressure and baseline fissure score (P = 0.003, P = 0.009, respectively). Although maximum anal resting pressure fell by 17 (mean, range, 0-71) percent, pressure reduction did not correlate with clinical outcome (P > 0.2). Seventeen patients reported a mean 17 percent increase in continence score. There was no correlation between deterioration in continence and baseline or subsequent reduction in maximum anal resting pressure. CONCLUSION: Patients with Grade 1 lower-pressure fissures are more likely to heal following treatment with 20 units of botulinum toxin. Healing does not appear to be dependent on a reduction in maximum anal resting pressure.

Adolescent↗
PubMed2005

Extracorporeal magnetic stimulation of the pelvic floor: impact on anorectal function and physiology. A pilot study.

PURPOSE: This study was designed to investigate the effect of extracorporeal magnetic stimulation on anorectal function and physiology. METHODS: A pilot study comparing the physiology of ten incontinent (9 females) and five continent (4 females) patients with and without perineal magnetic stimulation (10 Hz and 50 Hz) was performed. The ten incontinent patients were treated with two sessions weekly for five weeks of perineal magnetic stimulation. At treatment completion, precontinent and postcontinent scores and resting and squeeze anal pressure were compared. Patients also reported symptom improvement and satisfaction on a linear analog scale. RESULTS: The patients' mean age was 57 years. Sitting resting and squeeze anal pressures were significantly greater than lying pressures (P = 0.007, 0.047). Both 10-Hz and 50-Hz stimulation effected a significant increase in anal pressures compared with the baseline resting pressure (P = 0.005). The baseline squeeze pressures were significantly higher than the stimulated pressures compared with 50-Hz pressures (P = 0.022). After six weeks of treatment, there was a statistically significant increase in resting and squeeze anal pressures and a significant decrease in continence scores (P = 0.007, P = 0.008, P = 0.017). The mean percentage subjective improvement was 16 percent, and the mean patient satisfaction score was 3.3, positively correlating with an improvement in the continence score. CONCLUSIONS: Extracorporeal magnetic stimulation results in a significant increase in anal resting pressure irrespective of pretreatment continence. Although the subjective improvement in continence after treatment is small, there is a significant improvement in both resting pressures and patient continence scores.

Anal Canal↗
PubMed2005

The influence of victim characteristics on potential jurors' perceptions of brain damage in mild traumatic brain injury.

PRIMARY OBJECTIVE: To determine the influence of victim/plaintiff sex, occupation and intoxication status at the time of injury on potential jurors' judgement about the presence of brain damage in mild traumatic brain injury (MTBI). RESEARCH DESIGN: Survey. METHODS AND PROCEDURES: One of eight scenarios describing a MTBI from a motor vehicle accident was presented to 460 participants at a Department of Motor Vehicles. Victim sex, occupation (accountant or cafeteria worker) and alcohol intoxication status at the time of injury (sober or intoxicated) were manipulated across eight scenarios. Participants rated whether the victim's complaints at 6 months post-injury were the result of brain damage. MAIN OUTCOMES AND RESULTS: Ratings were influenced by victim occupation and intoxication status (chi2>5.3, p<0.03), but not the sex of the victim. CONCLUSIONS: The occupational and intoxication status of MTBI victims may influence potential jurors' decision about the presence of brain damage.

Accidents, Traffic↗
PubMed2004

Temporal and spatial genetic variability in white-tailed deer (Odocoileus virginianus).

Starch-gel electrophoresis was used to assess temporal and spatial genetic variation in populations of white-tailed deer (Odocoileus virginianus) in western Tennessee. Samples of liver and kidney obtained from animals at five localities during 1985-1992 were analyzed at 11 loci known to be polymorphic in white-tailed deer. There were minimal significant differences in allelic frequencies between sexes and among age groups for each year at each locality and among years at each locality with ages and sexes combined. No significant difference occurred among mean values of heterozygosity. A heterozygote deficiency was detected in white-tailed deer populations from western Tennessee and could reflect limited inbreeding but was more likely due to Wahlund effects. Limited temporal variation occurred among years within a locality and indicated a stasis in terms of minimal genetic drift and harvest effects on genetic structure of the populations. Herd origin, stocking history of populations, and gene flow were probable causes of spatial heterogeneity in deer populations in western Tennessee.

Animals↗
PubMed2004

Long-term follow-up of dynamic graciloplasty for faecal incontinence.

OBJECTIVE: This paper presents the long-term morbidity, function and quality of life data for patients who have undergone dynamic graciloplasty (DGP) for faecal incontinence. PATIENTS AND METHODS: All patients (n = 38) who had undergone DGP at one institution between 1993 and 2003 are presented. Thirty-three were available for long-term follow-up (median 60 months) and completed a telephone questionnaire assessing quality of life (QOL), bowel and sexual function and patient satisfaction. All patients had interval anorectal physiology studies. RESULTS: At a median follow-up of 5 years, 72% had pain, swelling or paraesthesia in the donor leg and 27% had sexual dysfunction. Sixteen percent of patients had been converted to an end-colostomy for persisting incontinence and 11% for obstructed defaecation. All other patients have a normally functioning graciloplasty. Sixteen percent of patients reported a faecal continence score < 12. Of those patients with a functioning graciloplasty, 50% had obstructed defaecation and 64% reported that their bowel dysfunction had a negative impacted on their QOL. Age, medical comorbidity and anal manometry did not correlate with functional outcome. Quality of life scores and patient satisfaction scores correlated significantly with continence scores. There was a trend toward higher QOL and satisfaction scores with conversion to colostomy compared with a continence score > 12. Sixty percent of patients rated their satisfaction with DGP as 50% or better on a visual analogue scale, and this correlated strongly with the continence score at the time of the assessment (P < 0.001). CONCLUSION: Dynamic graciloplasty significantly improves patient quality of life and anal continence for some patients. Despite increased experience, morbidity remains high and long-term continence scores are poor in a majority of cases. Obstructed defaecation is a significant problem after graciloplasty and antegrade colonic enemas may be needed. Significant prognostic factors for obstructed defaecation remain to be identified. The mechanism of both continence failure and surgical morbidity remains poorly defined in many patients and requires further investigation. The individual patient can expect a 16% chance of normal faecal continence at 5 years, with at least one surgical morbidity as a result of the procedure.

Adolescent↗
PubMed2002

Transanal endoscopic microsurgery excision: is anorectal function compromised?

PURPOSE: Transanal endoscopic microsurgery is a new technique that has not yet found its place in routine practice. The procedure results in dilation of the anal sphincter with a large-diameter operating sigmoidoscope, sometimes for a prolonged period. The purpose of the present study was to assess the effect of transanal endoscopic microsurgery on anorectal function. METHODS: Eighteen consecutive patients undergoing transanal endoscopic microsurgery excision of rectal tumors, of whom 13 were available for evaluation, were included. Continence was scored by a numeric scale before surgery and at three and six weeks after surgery. Anorectal physiology studies were performed preoperatively and six weeks postoperatively with manometry, pudendal nerve motor terminal latency, anal mucosal electrosensitivity, rectal balloon volume studies, and endoanal ultrasound. RESULTS: There was a significant reduction in mean anal resting pressure (104 +/- 32 cm H2O before surgery, 73 +/- 30 cm H2O after surgery; P = 0.0009). There was no significant change in squeeze or cough pressure, pudendal nerve terminal motor latency, anal mucosal electrosensitivity, or rectal balloon study volumes. Fall in resting pressure was significantly correlated with length of operating time (r2 =0.39, P = 0.047). There was no significant change in mean continence score after surgery. CONCLUSION: Transanal endoscopic microsurgery results in a reduction in internal sphincter tone. This did not affect continence in a short-term study.

Adult↗
PubMed2002

The proximal colonic motor response to rectal mechanical and chemical stimulation.

We aimed to determine whether rectal distension and/or infusion of bile acids stimulates propagating or nonpropagating activity in the unprepared proximal colon in 10 healthy volunteers using a nasocolonic manometric catheter (16 recording sites at 7.5-cm spacing). Sensory thresholds and proximal colonic motor responses were assessed following rectal distension by balloon inflation and rectal instillation of chenodeoxycholic acid. Maximum tolerated balloon volume and the volume that stimulated a desire to defecate were both significantly (P < 0.01) reduced after rectal chenodeoxycholic acid. The frequency of colonic propagating pressure wave sequences decreased significantly in response to initial balloon inflations (P < 0.05), but the frequency doubled after subsequent chenodeoxycholic acid infusion (P < 0.002). Nonpropagating activity decreased after balloon inflation, was not influenced by acid infusion, and demonstrated a further decrease in response to repeat balloon inflation. We concluded that rectal chenodeoxycholic acid in physiological concentrations is a potent stimulus for propagating pressure waves arising in the proximal colon and reduces rectal sensory thresholds. Rectal distension inhibits all colonic motor activity.

Adult↗
PubMed2001

Chemosensitization of a multidrug-resistant Leishmania tropica line by new sesquiterpenes from Maytenus magellanica and Maytenus chubutensis.

Parasite resistance to drugs has emerged as a major problem in current medicine, and therefore, there is great clinical interest in developing compounds that overcome these resistances. In an intensive study of South American medicinal plants, herein we report the isolation, structure elucidation, and biological activity of dihydro-beta-agarofuran sesquiterpenes from the roots of Maytenus magellanica (1-14) and M. chubutensis (14-17). This type of natural products may be considered as privileged structures. The structures of 10 new compounds, 1, 3, 6-9, and12-15, were determined by means of (1)H and (13)C NMR spectroscopic studies, including homonuclear (COSY and ROESY) and heteronuclear correlation experiments (HMQC and HMBC). The absolute configurations of eight hetero- and homochromophoric compounds, 1, 3,6-9, 12, and 13, were determined by means of CD studies. Fourteen compounds, 1-3 and 6-16, have been tested on a multidrug-resistant Leishmania tropica line overexpressing a P-glycoprotein-like transporter to determine their ability to revert the resistance phenotype and to modulate intracellular drug accumulation. From this series, 1, 2, 3, 14, and 15 showed potent activity, 1 being the most active compound. The structure-activity relationships of the different compounds are discussed.

ATP-Binding Cassette Transporters↗
PubMed2001

Metalloprotein and redox protein design.

Metalloprotein and redox protein design are rapidly advancing toward the chemical synthesis of novel proteins that have predictable structures and functions. Current data demonstrate a breadth of successful approaches to metallopeptide and metalloprotein design based on de novo, rational and combinatorial strategies. These sophisticated synthetic analogs of natural proteins constructively test our comprehension of metalloprotein structure/function relationships. Additionally, designed redox proteins provide novel constructs for examining the thermodynamics and kinetics of biological electron transfer.

Algorithms↗
PubMed2001

Do patients assess rectal bleeding accurately?

BACKGROUND: The accuracy of a patient's assessment of the volume of blood passed per rectum is unknown. The aim of the present study was to compare subjective estimations with known amounts of blood. METHODS: Thirty subjects (10 patients, 10 nurses and 10 doctors) made a visual estimation of four volumes of blood (0.25 mL, 10 mL, 50 mL, 200 mL), each placed in a standardized way into a toilet bowl. Subjects gave their estimations in mL, and also by drawing a line on a cup at the level to which they estimated that the amount of blood would fill the cup. Statistical analysis was carried out using Student's t-test. Multiple comparisons were analysed by anova. RESULTS: There was no significant difference between the groups in their estimations of each of the four volumes. Each group made a statistically significant overestimation for the 0.25 mL, 10 mL and 50 mL volumes with cup marking, as well as with estimation in mL (except for patients with the 50 mL volume, where there was a non-significant overestimation). For the 200 mL volume, patients and doctors made statistically significant underestimations with cup marking, but for nurses the underestimation did not reach significance. For the 200 mL volume estimations in mL, both nurses and doctors made underestimations that were not significant. CONCLUSIONS: Small to moderate amounts of blood in the toilet bowl are subjectively significantly overestimated, whereas larger volumes tend to be underestimated. This may have implications for the management of patients presenting with rectal bleeding.

Adult↗
PubMed2001

Prolonged multi-point recording of colonic manometry in the unprepared human colon: providing insight into potentially relevant pressure wave parameters.

OBJECTIVES: To determine the feasibility of and derive normative data for prolonged, 24-h, multipoint, closely spaced, water perfused manometry of the unprepared human colon. METHODS: In 14 healthy volunteers, 24-h recordings were made using a water perfused, balloon-tipped, 17 lumen catheter which was passed pernasally and positioned so that 16 recording sites spanned the colon at 7.5 cm intervals from cecum to rectum. The area under the pressure curve and propagating pressure wave parameters were quantified for the 16 regions. High amplitude propagating sequences were defined as were rectal motor complexes. RESULTS: Nasocolonic recording was well tolerated and achievable. Propagation sequences, including high amplitude propagating sequences, originated in the cecum (0.32 +/- 0.05/h) more frequently than in other regions and the extent of propagation correlated significantly with proximity of the site of sequence origin to the cecum (p < 0.001). Propagation velocity of propagating sequences was greater than high amplitude propagating sequences (p = 0.0002) and region-dependent, unlike high amplitude propagating sequences (p < 0.01). The frequency of propagating sequences did not increase after the meal, but frequency of high amplitude propagating sequences was increased significantly by the meal (p < 0.01). Rectal motor complexes were seen throughout the colon with no apparent periodicity. CONCLUSIONS: Prolonged, multipoint, perfusion manometry of the unprepared colon provides improved spatial resolution of colonic motor patterns and confirms the diurnal and regional variations in propagating pressure waves detected in the prepared colon. The study demonstrates differences between high amplitude propagating sequences and propagating sequence parameters that may have functional significance; and also, that the rectal motor complex is a ubiquitous pan colonic motor pattern.

Adult↗
PubMed2000

Spatial and temporal organization of pressure patterns throughout the unprepared colon during spontaneous defecation.

OBJECTIVE: The aim of this study was to examine colonic motor events associated with spontaneous defecation in the entire unprepared human colon under physiological conditions. METHODS: In 13 healthy volunteers a perfused, balloon-tipped, 17-lumen catheter (outer diameter, 3.5 mm; intersidehole spacing, 7.5 cm) was passed pernasally and positioned in the distal unprepared colon. RESULTS: In the hour before spontaneous defecation, there was an increase in propagating sequence frequency (p = 0.04) and nonpropagating activity when compared to basal conditions (p < 0.0001). During this hour the spatial and temporal relationships among propagating sequences demonstrated a biphasic pattern. Both the early (proximal) and late (distal) colonic phases involved the whole colon and were characterized by respective antegrade and retrograde migration of site-of-origin of arrays of propagating sequences. There was a negative correlation between propagating sequence amplitude and the time interval from propagating sequence to stool expulsion (p = 0.008). CONCLUSIONS: The colonic motor correlate of defecation is the colonic propagating sequence, the frequency and amplitude of which begin to increase as early as 1 h before stool expulsion. During the preexpulsive phase, the spatial and temporal relationship among the sites of origin of individual propagating sequences demonstrate a stereotypic anal followed by orad migration, which raises the possibility of control by long colocolonic pathways.

Adult↗
PubMed1999

Glyceryl trinitrate ointment for the treatment of chronic anal fissure: results of a placebo-controlled trial and long-term follow-up.

PURPOSE: A randomized, double-blind, placebo-controlled trial was performed to test the effect of intra-anal glyceryl trinitrate ointment in patients with chronic anal fissures that would normally have been treated by sphincterotomy. Long-term follow-up was then performed to assess fissure healing. METHODS: Patients with chronic anal fissures were randomly assigned to 0.2 percent topical glyceryl trinitrate ointment or placebo. Anal manometry was performed before treatment, one week later, and 48 hours after treatment ceased at four weeks. Fissure healing was assessed by an observer blinded to the treatment arm. Pain was recorded on a linear analog scale. At the completion of the trial, treatment was continued with glyceryl trinitrate until fissure healing was obtained or lateral sphincterotomy was performed if required for ongoing pain. A long-term follow-up assessment was made at a mean of 29 (range, 25-33) months. RESULTS: There was a significant reduction in anal resting pressure at Week 1 with glyceryl trinitrate (P = 0.001) but not placebo, and at Week 4 there was a significant reduction in pain score with glyceryl trinitrate (P = 0.001) and placebo (P = 0.01) and a significant reduction in fissure grade with glyceryl trinitrate (P = 0.0001) and placebo (P = 0.02). Forty-six percent of fissures healed with glyceryl trinitrate and 16 percent healed with placebo (P = 0.001). At long-term follow-up in 40 of 43 patients, 14 patients (35 percent) had undergone lateral sphincterotomy, and in the remainder who were treated with glyceryl trinitrate there was a significant reduction in pain score (P = 0.0002). Seventeen patients attended for repeat manometry and fissures were healed with glyceryl trinitrate in ten (59 percent) cases. High internal sphincter pressures persisted at long-term follow-up in patients successfully treated with glyceryl trinitrate, indicating that the sphincter is the cause rather than effect of anal fissure. CONCLUSION: Topical glyceryl trinitrate produces a successful internal sphincterotomy, which resulted in long-term healing of 59 percent of chronic anal fissures and significant improvement in pain. Internal sphincter spasm is the cause of chronic anal fissure.

Administration, Topical↗