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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
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↗
PubMed1999

Basal pressure patterns and reflexive motor responses in the human ileocolonic junction.

This study aimed to determine whether a sustained high-pressure zone exists at the human ileocolonic junction (ICJ) and whether the motor responses of ICJ are consistent with sphincteric function. In 10 subjects with temporary ileostomies, a high-pressure zone was identified using a manometric pull-through with a mean pressure of 9. 7 +/- 3.2 mmHg and length of 4.8 +/- 1.2 cm. Prolonged recordings using a sleeve sensor confirmed sustained tone in the ICJ and superimposed phasic pressure waves (4-8 counts/min) occupying 35% of fasted state. A meal increased ICJ tone (P = 0.0001) and the proportion of time occupied by phasic activity to 50% (P = 0.013). Terminal ileal propagating pressure wave sequences inhibited ICJ phasic activity, and sequences not extending to the cecum reduced ICJ tone (9.0 +/- 7.2 to 5.6 +/- 6.3 mmHg; P = 0.04). Cecal distension increased ICJ tone (8.9 +/- 4.4 mmHg to 11.7 +/- 4.9 mmHg; P = 0.005). The ICJ response to ileal distension was variable and depended on resting tone at the time of distension. We conclude that the human ICJ has sustained tone with superimposed phasic activity. Tone is augmented by cecal distension or a meal and is inhibited by ileal propagating pressure waves. Response to ileal distension is variable but suggests control by descending excitatory and inhibitory pathways.

Adult↗
PubMed1999

Relationship between terminal ileal pressure waves and propagating proximal colonic pressure waves.

The relationship between propagating distal ileal and proximal colonic motor patterns has not been systematically examined in humans. Our aim was to define the relationships, if any, between prolonged propagating contractions or discrete clustered contractions and cecal propagating sequences using multiple manometric recording sites spanning the distal ileum and unprepared colon. In 14 healthy volunteers, a 17-lumen-perfused silicon catheter was positioned pernasally such that at least three recording sites lay in the ileum and the remainder in the colon. Intersidehole distance was 7.5 cm. In 271 h of recording, 30% of the terminal ileal propagating events was temporally associated with cecal propagating sequences. Significantly more prolonged propagating contractions (11 of 24, 46%; P = 0.02) were associated with cecal propagating sequences than were associated with ileal discrete clustered contractions (4 of 26, 15%). This trend was more pronounced at night. Of 159 cecal propagating sequences, 15 (9%) were preceded by an ileal propagating event. The remaining 91% was preceded by increased nonpropagating activity commencing 2 min before the cecal propagating sequence (P = 0.0002). We conclude that distal ileal propagating motor patterns are one stimulus for cecal propagating sequences, with the association being stronger for prolonged propagating contractions than for discrete clustered contractions.

Adult↗
PubMed1999

A comparison of nine WAIS-R short forms in individuals with mild to severe traumatic brain injury.

Scores from nine WAIS-R short forms were calculated for a sample of 75 adults with mild to severe traumatic brain injury (TBI). Although all nine of the short forms were significantly correlated with the WAIS-R Full Scale IQ, three of the short forms (Vocabulary-Block Design; Vocabulary-Block Design-Arithmetic-Similarities; Vocabulary-Arithmetic-Picture Arrangement-Block Design) significantly overestimated the WAIS-R IQ and thus may be inappropriate to use with this population. The remaining six short forms did not differ significantly from the WAIS-R Full Scale IQ. Among these six, Ward s seven-subtest short form appeared to exhibit the least variability in predicting the WAIS-R Full Scale IQ. Information is presented and discussed regarding the absolute difference scores between short form IQ estimates and the WAIS-R as well as the proportion of short forms which significantly under- and overestimate the Full Scale IQ.

Adult↗
PubMed1997

Effect of iron on transferrin receptor expression by human placental syncytiotrophoblast cells.

Transferrin receptor expression has been examined in primary cultures of morphologically differentiated placental syncytiotrophoblast cells. More than 90% of the cells were multinucleated. Incubation of syncytiotrophoblast for 4 days in the presence of iron salts had no effect on receptor expression assessed by measuring the binding of 125I-labelled transferrin. However, incubation of cells in the presence of human diferric transferrin (10-100 microM) led to a 50% decrease in surface and intracellular receptor expression. This down-regulation was not accompanied by a significant decrease in receptor synthesis. In contrast to syncytiotrophoblast, expression of intracellular transferrin receptors in non-differentiated cytotrophoblast cells decreased when cells were cultured with iron salts; this was accompanied by decreased receptor synthesis. Addition of diferric transferrin to cytotrophoblast cells led to a 50% reduction in surface and intracellular receptor expression, similar to that seen in the syncytiotrophoblast. This reduction was accompanied by a decrease in receptor synthesis. In contrast to that of most cell types, the expression and distribution of trophoblast transferrin receptors were not altered by insulin, epidermal growth factor or hydrocortisone. These characteristics of syncytiotrophoblast transferrin receptor expression may assist in ensuring a supply of iron to the fetus regardless of the maternal iron status.

Cells, Cultured↗
PubMed1997

Robertsonian chromosomal rearrangements in the short-tailed shrew, Blarina carolinensis, in western Tennessee.

We report significant heterozygosity for numerous Robertsonian translocations in the southern short-tailed shrew (Blarina carolinensis) in western Tennessee. Eight Robertsonian rearrangements were documented using G-banding techniques that explain the variability in diploid numbers from 46 throughout most of the range of the species to 34-40 in western Tennessee. These fusions resulted in the loss of telomere sequences and were not associated with nucleolar organizer regions. When heterozygocity is considered, the lowest diploid number possibly present would be 30. Four localities with distances of over 180 km apart were sampled, and 80-90% of the collected animals were heterozygous for at least one rearrangement. No putative parental type was found in western Tennessee. Heterozygosity for the same rearrangements was found in these different localities, and no monobrachial fusions were noted. Thus, this is a very wide hybrid zone with rare or absent parental types in the areas sampled or is an evolutionary stage preceding establishment of Robertsonian races. Selective forces, if any, were minimal, as evidenced by the wide area of polymorphism, significant heterozygosity, and the fact that the Robertsonian translocations were in Hardy-Weinberg equilibrium. The origin of such extensive polymorphism in western Tennessee is discussed, especially in light of putative effects of the New Madrid seismic activity. Similarities and differences are noted between the Blarina model and the well-documented variation in the European common shrew (Sorex araneus) and Mus musculus groups.

Animals↗
PubMed1996

Chromosomal variation in the southern short-tailed shrew (Blarina carolinensis).

Chromosomal polymorphism was assessed in the southern short-tailed shrew (Blarina carolinensis) using standard metaphase chromosome and G-banding techniques. Twenty-one animals (11 males, 10 females) from the Meeman Biological Station in Shelby Co., Tennessee, were examined for diploid number. Results showed diploid numbers of 35, 36, 37, 38, 39, 40 and 41 and fundamental numbers of 41, 42, 43, 44 and 45. No diploid numbers or fundamental numbers were unique to a specific collecting locality. The first G-banded karyotypes are reported for the species. These results indicate that Robertsonian polymorphisms, inversions, and possibly other events are responsible for chromosomal variation in B. carolinensis.

Animals↗
PubMed1996

Rectal mucosal electrosensitivity - what is being tested?

The results of rectal mucosal electrosensitivity (RME) testing have been used to support theories regarding the aetiology of both idiopathic constipation and bowel dysfunction following rectopexy. The aim of this study was to assess the validity of tests of RME. Sixty-eight patients, comprising three groups (group 1: 50 patients undergoing assessment in the Anorectal Physiology Unit, group 2: 10 patients with coloanal or ileoanal anastomosis, group 3: 8 patients with a stoma) underwent mucosal electrosensitivity testing, with the threshold stimulus required to elicit sensation being recorded. In addition the RME was measured in groups 1 and 2 when placing the electrode, mounted on a catheter with a central wire, against the anterior, posterior, right and left rectal or neorectal walls. To asses the influence on this test of loss of mucosal contact due to faeces, a further 8 cases with a normal rectum had RME performed with and without a layer of water soaked gauze around the electrode to stimulate faeces and prevent the electrode from making contact with the rectal mucosa. There was marked variance in the sensitivity of the different regions of rectal wall tested (P < 0.001). In group 1 patients the mean sensitivities were: central 36.6 mA, anterior 27.4 mA, posterior 37.9 mA, right 22.3 mA and left 25.6 mA. This circumferential variation suggests that the pelvic floor rather than rectal mucosa was being stimulated. All patients in group 2 had recordable sensitivities, and the mean sensitivity threshold was significantly higher than group 1 patients in the central (P = 0.03), right (P = 0.03) and left (P = 0.007) positions. In group 3 the sensitivity was greater within the stoma at the level of the abdominal wall muscle than intra-abdominally or subcutaneously, again suggesting an extra-colonic origin of the sensation. The sensitivity threshold was significantly greater with the electrode wrapped in gauze (P < 0.01), and loss of mucosal contact was not detected by the EMG machine. Therefore RME testing would seem not to measure mucosal sensitivity, and is probably influenced by the presence of faeces.

Electric Stimulation↗
PubMed1996

Results of colectomy for severe slow transit constipation.

PURPOSE: This study assesses the outcome of a standardized operation performed by two surgeons for severe idiopathic slow transit constipation that was resistant to laxative treatment. METHODS: Fifty-nine consecutive patients, 4 men and 55 women, with a mean age of 42.3 years, underwent colectomy with ileorectal anastomosis. Slow colonic transit was demonstrated in each case. Fifty-two patients were available for follow-up, with median time to follow-up being 42 (range, 3-81) months. RESULTS: Median bowel frequency was 4 per 24 hours. Sixty-nine percent had four or less bowel movements daily. Ten percent used antidiarrheal medication regularly. One patient had a stoma for recurrent severe constipation. Mean continence score was 1.8 (on a scale of 0-20); six patients were incontinent, and four of these six had normal preoperative anal manometry. Fourteen patients (27 percent) had difficulty with rectal evacuation. Preoperative defecating proctography was a poor predictor of postoperative evacuation difficulties. Twenty-seven patients (52 percent) had persisting abdominal pain, but there was a significant improvement in the degree of pain (P <0.00001). Forty-seven patients (90 percent) were satisfied with the outcome of the operation (and would elect to have it done again). Dissatisfied patients had recurrent constipation or diarrhea and incontinence. CONCLUSION: Colectomy with ileorectal anastomosis produces a satisfactory functional outcome in the majority of patients undergoing surgery for severe constipation with proven slow colonic transit.

Adolescent↗