The antihypertensive and diuretic effect of crude root extract and saponins from Solanum sisymbriifolium Lam., in L-NAME-induced hypertension in rats.

ETHNOPHARMACOLOGICAL RELEVANCE: Solanum sisymbriifolium Lam., is used in Paraguayan folk medicine claiming antihypertensive and diuretic properties. AIM OF THE STUDY: This study aimed to determine the influence of chronic oral administration of the crude root extract and saponins obtained from S. sisymbriifolium Lam., on the blood pressure of male and female rats with hypertension induced by L-NAME, and its consequences on diuresis, the body weight, blood glucose, and level of serum parameters of liver and kidney functionality. MATERIALS AND METHODS: Wistar rats were randomly divided into seven male, and seven female groups (8 animals each), which received as 6-week pretreatment, 0.9% saline solution (two groups; 0.1mL/10 g of b.w.), L-arginine (100.0 mg/kg/day), enalapril (15.0 mg/kg/day), crude extract (CESs 100.0 mg/kg/day), and saponin purified fraction (1.0, and 10.0 mg/kg/day), and treated with L-NAME (20 mg/kg/day/i.p.) twice, 1, and 6 h after pre-treatment. The animals' body weight, glycemia, and blood pressure were recorded weekly, while serum, hepatic, renal, and histological parameters were analyzed at the end of 6-week of treatment. RESULTS: A protective effect of CESs (100.0 mg/kg/day), and saponins (1.0, and 10.0 mg/kg/day) against hypertension induced by L-NAME was verified in the systolic, diastolic, and mean blood pressure values, which were significantly lower than the positive L-NAME-hypertensive control group (male and female) at the end of the 6-week treatment. Also, pretreatment with enalapril (15.0 mg/kg/day) induced an efficient protective activity, which validates the method used. Likewise, the volume of urine, creatinine, uric acid, urea, and electrolyte excretion was enhanced at the end of 6-week of treatment in concordance with the reduction in serum level of the same parameters, compatible with the improvement of the diuretic activity. The glycemia, body weight, heart rate, and functional hepato-renal parameters were not modified after a 6-week of treatment, in comparison to the control group, indicating relatively acceptable harmless properties of CESs and saponins. Interestingly, the HDL level in females was increased in contrast to male rats by chronic saponins treatment when compared with the negative control group. CONCLUSIONS: It can be concluded that either the increment in blood pressure (systolic, diastolic, and median) or cardiorenal remodeling effects in male and female rats submitted to L-NAME-induced hypertensive condition, were prevented and well-preserved without a significant variation during a period of 6-week of pretreatment with CESs and saponins pretreatments. Likewise, an important diuretic effect was revealed after this period of treatment.

No Evidence of Competition Between the Blacklegged Tick (Acari: Ixodidae) and American Dog Tick on the Rodent Host White-Footed Deermouse (Rodentia: Cricetidae) in Southwestern Tennessee.

Investigations that analyze interspecific associations of vectors on their hosts are important for understanding community structure and implementing ways to comprehend mechanisms of pathogen transmission. We assessed the interspecific association of two tick species (Ixodes scapularis Say (Ixodida: Ixodidae) and Dermacentor variabilis Say (Ixodida: Ixodidae)) on the rodent host Peromyscus leucopus Rafinesque (Rodentia: Cricetidae) at the Hobart Ames Research and Education Center in southwestern Tennessee. Of the rodents captured, 95 (63%) had neither species of tick, 6 (4%) had both tick species, 25 (16%) had I. scapularis only, and 26 (17%) had D. variabilis only. A coefficient of association (C7 = -0.08) was calculated, which suggested there was competition between the two species of ectoparasites, but this value was not significant, indicating that there was a neutral relationship between the tick species on P. leucopus. The co-occurrence of both tick species on their host at the same time suggested that the two tick species can occupy the same host and use the same resources without competing.

Small-mammal characteristics affect tick communities in southwestern Tennessee (USA).

Life histories can influence the degree of parasite infestations on a host. Pressures exerted on hosts based on age and sex convey varying degrees of parasite prevalence due to differences in host lifestyles, but it is not known how interactions between different host traits affect tick numbers. The objective of this study was to determine if host characteristics (e.g., age, sex, weight, and their interactions) affect the mean number of ticks found on small mammals regardless of host species or habitat. Sherman live traps were placed in forest and grass/forb habitats representative of the southeastern United States. After capture, host characteristics were recorded, and hosts were then searched for ticks. A total of 281 small mammals (148 Peromyscus leucopus, 34 P. maniculatus, 76 Sigmodon hispidus, 16 Microtus pinetorum, and 7 Ochrotomys nuttalli) and 610 ticks (488 Dermacentor variabilis, 114 Ixodes scapularis, 1 Amblyomma americanum, and 7 A. maculatum) were collected in this study. Host's age, sex, and weight affected the number of ticks collected from small mammals and significant interaction effects between host traits occurred (weight by sex, weight by age, and sex by age). For instance, female subadult rodents had significantly more ticks compared to female adults, male subadults had significantly fewer ticks compared to male adults, and the number of ticks on a host increased as host body mass increased. These results support the hypothesis that the number of ticks vary on rodent hosts based on life histories and trait interactions. Therefore, understanding the behavioral mechanisms of a host can aid in the management of parasites in the environment.

Antidepressant-like effect of Kyllinga brevifolia rhizomes in male mice and chemical characterization of the components of the active ethyl acetate fraction.

ETHNO-PHARMACOLOGICAL RELEVANCE: Kyllinga brevifolia rhizomes (Cyperaceae) are used in Paraguayan traditional medicine as a refreshing beverage, and is claimed to own digestive, diuretic, sedative, tonic, antispasmodic and sudorific properties. We have previously reported that its hydro- ethanolic rhizome extract possess sedative, anxiolytic and anti-aggressive-like effects in mice. However, information on its potential for treatment of syndromes associated with mood disorders is scarce. AIM OF THE STUDY: The purpose of this study is to characterize the putative antidepressant-like effects of the hydro-ethanolic extract (CEKb) and the ethyl acetate fraction (KbF-ethyl-ac) obtained from the rhizome of K. brevifolia (Rottb) on male mice exposed to forced swimming test. Also, chemical characterization of the components of the active ethyl acetate fraction was described. MATERIALS AND METHODS: The antidepressant-like effects of CEKb and KbF-ethyl-ac were measured using the forced swimming test (FST) performance of male mice in single (acute), short-term and chronic modalities. Treatments in all modalities were made 1h before swimming test. The KbF-ethyl-ac was analyzed by LC-DAD-ESI-MS and LC-ESI-MS/MS in order to identify the active components. RESULTS: A single doses (1.0, 10.0 and 100.0mg/kg, p.o; p<0.05) of CEKb, in male mice provoked a significant reduction of the immobility time. Such effect was also observed with oral short-term treatment (7 days) with doses of 10.0 and 100.0mg/kg/day (p<0.05) of CEKb. Moreover, in the treatments during 14 days with doses of 1.0 (p<0.05), 10.0 (p<0.05), and 100.0 (p<0.001) mg/kg, p.o, of CEKb, a statistically significant reduction of the immobility time were induced. Additionally, in a different set of experiments acute dose of 1.0 (p<0.05) and 10.0 (p<0.01) mg/kg, p.o, of KbF-ethyl-ac in male mice, a significant reduction of the immobility time were provoked. Likewise, short-term treatment (7 days) with 1.0, and 10.0mg/kg (p<0.05); and after 14 days of treatment with 0.01 (p<0.01) 0.1 (p<0.001), 1.0 (p<0.001), and 10.0 (p<0.05) mg/kg of KbF-ethyl-ac in male mice, a statistically significant reduction of the immobility time, were observed. Imipramine 32mg/kg/days, i.p, induced a statistically significant reduction of immobility time and was used as positive control to validate the method employed. Moreover, it was noted important differences in the onset of the antidepressant-like effect in the FST, depending on the modality of treatment with CEKb or KbF-ethyl-ac (acute, short-term or chronic). Both, efficacy and potency were higher when repeated administration of CEKb was used, and surprisingly the efficacy of 1.0mg/kg of KbF-ethyl-ac (14 days) was similar to imipramine. The main constituents of the KbF-ethyl-ac were identified as catechins and their dimers by LC-DAD-ESI-MS and LC-ESI-MS/MS, according to their UV and MS spectra, as compared with the literature data. These results indicate an important antidepressant-like profile of action for the CEKb and KbF-ethyl-ac; and meanwhile, this effect may partially reside on catechins and their dimers isolated from the KbF-ethyl-ac. CONCLUSION: These findings indicate that K. brevifolia exerts antidepressant -like effects in mice and suggest its potential usefulness for the treatment of depression in humans and encourage us to pursue the isolation of the molecules associated to the effect observed in CEKb and KbF-ethyl-ac, and to determine the mechanism of antidepressant-like effect of Kyllinga brevifolia using adequate complementary test.

Antihypertensive effect of nuatigenin-3-O-ß-chacotriose from Solanum sisymbriifolium Lam. (Solanaceae) (ñuatî pytâ) in experimentally hypertensive (ARH+DOCA) rats under chronic administration.

The aim of the study is to assess the hypotensive properties of the hydro-ethanolic crude root extract (CRE), the n-butanol fraction (F(BtOH)) and nuatigenin-3-O-ß-chacotriose, from Solanum sisymbriifolium Lam., in adrenal regeneration hypertension+deoxycorticosterone acetate (ARH+DOCA) rats, following a chronic administration. The roots of S. sisymbriifolium Lam. (Solanaceae) were extracted by reflux with ethanol-water 7:3 and the active extract was fractionated by bioassay-guided liquid-liquid separation. Nuatigenin-3-O-ß-chacotriose (B(3-1)) was identified as the main hypotensive compound from the crude drug by spectroscopic methods. Immature Wistar rats of both sexes were submitted to both surgery and deoxycorticosterone acetate treatment to obtain adrenal regeneration hypertensive rats (ARH+DOCA). Different groups of experimentally induced hypertensive rats were randomly allotted and received during 16 weeks a daily oral administration of 1% saline solution (0.1 mL/100g body weigh), 100.0 mg/kg of CRE, 10.0, 30.0 and 50.0 mg/kg of F(BtOH), and 1.0 mg/kg of B(3-1), respectively. In addition, two groups of ARH+DOCA rats were randomly assigned to receive either B(3-1) (1.0 mg/kg/day) or 1% of saline solution (0.1 mL/100g body weight/day) for 7 weeks and then a cross over procedure was performed in order to complete the 16th-week treatment. After 16 weeks of oral administration of crude root extract (CRE), butanolic fraction (F(BtOH)) and nuatigenin-3-O-ß-chacotriose (B(3-1)) a significant reduction of blood pressure value was induced in hypertensive animals (ARH+DOCA) in comparison to the control group receiving 1% saline solution, at the end of experiment. Administration of B(3-1) (1.0 mg/kg/day p.o.) to ARH+DOCA rats provoked a significant reduction of blood pressure, observed gradually from 5th week (p<0.05) to the end of the 16th week period of treatment (p<0.01). Moreover, in a cross over design it was observed that the reduction of blood pressure to normotensive condition is associated to B(3-1). The latest demonstrated that the blood pressure-lowering effect, in clearly hypertensive animals, is reversible and depend upon administration of nuatigenin-3-O-ß-chacotriose (B(3-1)). Our results demonstrated that daily oral administration of CRE, F(BtOH) and nuatigenin-3-O-ß-chacotriose from S. sisymbriifolium for a 16-week period exhibits an antihypertensive effect in experimentally hypertensive (ARH+DOCA) rats.

Postanal repair--do the long-term results justify the procedure?

OBJECTIVE: Early outcomes after postanal repair (PAR) demonstrated excellent results but subsequent reports showed an ever declining success rate in maintaining continence. The aim of this study was to document long-term continence after PAR and relate this to patient satisfaction and quality of life. METHOD: Patients with neurogenic incontinence who underwent PAR from 1986 to 2002 were interviewed by telephone, utilizing a questionnaire which assessed continence, patient satisfaction, overall improvement, and quality of life. RESULTS: One-hundred one patients from four surgeons were identified. Fifty-four patients were excluded because of loss to follow-up. Three had a stoma (two for incontinence), four had undergone a graciloplasty, leaving 57 patients (F = 53), mean duration of follow-up of 9.1 years (2.2-18.7 years). Mean CCS was 11.7 (SD 7.4). 26% (n = 15) scored none to minimal incontinence (CCS 0-5), 26% moderate (CCS 6-12), and 48% (n = 27) severe incontinence (CCS 13-24). 79% (n = 45) were satisfied with the outcome. A low CCS significantly correlated with good patient satisfaction, and was influenced by high QOL score (P < 0.0001). A high CCS significantly correlated with high bowel frequency (P = 0.0007). A favourable CCS was associated with a good QOL, a shorter duration of follow-up, and being able to distinguish flatus and stool. CONCLUSIONS: In patients with neurogenic faecal incontinence selected following anorectal physiology studies, PAR remains a useful treatment. It is associated with low morbidity and results in a satisfactory long-term subjective outcome, despite the fact that many patients have a high incontinence score.

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

The aim of the present work is to evaluate the putative antidepressant-like effects of a hydro-ethanolic extract (CEAp) and their fractions from the aerial parts of Aloysia polystachya (Griseb.) Moldenke (Verbenaceae) on the performance of male mice in the forced swimming test (FST). A single dose (100.0mg/kgp.o.) of CEAp, in male mice provoked a significant reduction of the immobility time (p<0.01). Such effect was also observed with short-term treatment (7 days) with single doses of 1.0 (p<0.01), 10.0 (p<0.05) and 100.0 (p<0.05)mg/kg/day of CEAp. Additionally, in a different set of experiments, repeated administration in a 24-h period (24, 18 and 1h before swimming test) with doses of 1.0 (p<0.05) and 10.0 (p<0.05)mg/kg p.o., of CEAp and 10.0mg/kgp.o., (p<0.05) of ethyl acetate fraction, provoked significant reduction of the immobility time of male mice in the FST. Moreover, it was noted important differences in the onset of the antidepressant-like effect in the FST, depending on the modality of treatment with CEAp (acute, short-term or repeated). Both, efficacy and potency were higher when repeated administration of CEAp was used, and surprisingly the dose of 10mg/kg (24, 18 and 1h before swimming test) was more effective than imipramine. In the same way, the short term administration (7 days) improved significantly efficacy and potency of the CEAp in comparison to a single dose treatment. The ethyl acetate fraction submitted to TLC demonstrated that main and minor components are phenolics and terpenes, respectively. In addition, this fraction gives a negative Shinoda's test for flavonoids. These results indicate an antidepressant-like profile of action for the hydro-ethanolic extract and the component(s) of the ethyl acetate fraction obtained from A. polystachya, which deserve further investigation.

Rectogesic (glyceryl trinitrate 0.2%) ointment relieves symptoms of haemorrhoids associated with high resting anal canal pressures.

OBJECTIVE: Some haemorrhoids are associated with high resting anal canal pressures. The aim of this study was to assess if Rectogesic, a topical glyceryl trinitrate 0.2% ointment was effective in relieving symptoms of early grade haemorrhoids associated with high resting anal canal pressures. METHOD: This was a prospective, two-centre, open label study of 58 patients with persistent haemorrhoidal symptoms. Patients with first or second degree haemorrhoids and a maximum resting anal canal pressure > 70 mmHg were included. Rectogesic was applied three times a day for 14 days. Anorectal manometry was performed 30 min after the first application of Rectogesic. A 28-day diary was completed during 14 days of therapy and for 14 days after cessation of treatment. This recorded the incidence of rectal bleeding, and visual analogue scales for anal pain, throbbing, pruritus, irritation and difficulty in bowel movement. RESULTS: Maximum resting anal canal pressures were reduced after application of Rectogesic (115.0 +/- 40.4 mmHg vs 94.7 +/- 34.1 mmHg, P < 0.001). In the study period and at 14 days after cessation of Rectogesic, there was significant reduction in rectal bleeding (P = 0.0002), and significant improvement of anal pain (P = 0.0024), throbbing (P = 0.0355), pruritus (P = 0.0043), irritation (P = 0.0000) and difficulty in bowel movement (P = 0.001). The main adverse event was headache in 43.1% of patients. CONCLUSION: Rectogesic is a safe and feasible treatment for patients with early grade haemorrhoids associated with high resting anal canal pressures.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.