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Biomedical subjects

A M Leroi

Publications and source records attributed to A M Leroi.

At least 19 recordsLinked to original sources
PubMed2003

ALES: cell lineage analysis and mapping of developmental events.

MOTIVATION: Animals build their bodies by altering the fates of cells. The way in which they do so is reflected in the topology of cell lineages and the fates of terminal cells. Cell lineages should, therefore, contain information about the molecular events that determined them. Here we introduce new tools for visualizing, manipulating, and extracting the information contained in cell lineages. Our tools enable us to analyze very large cell lineages, where previously analyses have only been carried out on cell lineages no larger than a few dozen cells. RESULTS: Ales (A Lineage Evaluation System) allows the display, evaluation and comparison of cell lineages with the aim of identifying molecular and cellular events underlying development. Ales introduces a series of algorithms that locate putative developmental events. The distribution of these predicted events can then be compared to gene expression patterns or other cellular characteristics. In addition, artificial lineages can be generated, or existing lineages modified, according to a range of models, in order to test hypotheses about lineage evolution. AVAILABILITY: The program can run on any operating system with a compliant Java 2 environment. Ales is free for academic use and can be downloaded from http://mbi.dkfz-heidelberg.de/mbi/research/cellsim/ales.

Algorithms↗
PubMed2002

Does water-perfused catheter overdiagnose anismus compared to balloon probe?

BACKGROUND: The purpose of this study was to compare the manometric assessment of straining effort as if to defecate and rectoanal inhibitory reflex obtained with a rectosphincteric balloon probe and with a water-perfused catheter in the same subject. METHODS: Twelve healthy volunteers underwent two manometric assessments of anal sphincter function and electromyographic (EMG) surface recordings. one with a rectosphincteric balloon and one with a water-perfused catheter, 7 days apart in random order. RESULTS: Increased EMG activity in the external anal sphincter in the midst of the rectoanal inhibitory reflex (P < 0.001) and during straining for defecation (P < 0.001) was more frequently observed with the perfused system than with the balloon probe. There was a discrepancy between the EMG activity of the external anal sphincter and the anal pressures during straining recorded with the perfused system. Duration of the reflex elicited by rectal distension with 10 and 20 ml of air was significantly greater with the rectosphincteric balloon than with the perfused catheter (P = 0.02 and P = 0.05, respectively). CONCLUSION: Water instilled in the anal canal by the perfused system induces artifacts in EMG recording and active anal contractions. These artifacts and induced contractions could lead to an erroneous diagnosis of anismus, particularly if pelvic floor EMG is only taken into account for the diagnosis of anismus.

Adult↗
PubMed2001

A power law for cells.

Darwin observed that multiple, lowly organized, rudimentary, or exaggerated structures show increased relative variability. However, the cellular basis for these laws has never been investigated. Some animals, such as the nematode Caenorhabditis elegans, are famous for having organs that possess the same number of cells in all individuals, a property known as eutely. But for most multicellular creatures, the extent of cell number variability is unknown. Here we estimate variability in organ cell number for a variety of animals, plants, slime moulds, and volvocine algae. We find that the mean and variance in cell number obey a power law with an exponent of 2, comparable to Taylor's law in ecological processes. Relative cell number variability, as measured by the coefficient of variation, differs widely across taxa and tissues, but is generally independent of mean cell number among homologous tissues of closely related species. We show that the power law for cell number variability can be explained by stochastic branching process models based on the properties of cell lineages. We also identify taxa in which the precision of developmental control appears to have evolved. We propose that the scale independence of relative cell number variability is maintained by natural selection.

Animals↗
PubMed2001

Effect of sacral nerve stimulation in patients with fecal and urinary incontinence.

PURPOSE: Preliminary studies have shown improvement in fecal incontinence in several patients who received temporary or permanent stimulation. The purpose of this study was to report our experience in sacral nerve stimulation in the treatment of fecal incontinence and to target patients who would benefit most from stimulation. METHODS: Patients with fecal incontinence were studied clinically and manometrically before, during, and after temporary nerve stimulation. If temporary nerve stimulation was clinically successful, the patient was implanted and followed up for six months. RESULTS: Nine patients (6 female) with a mean age of 50.7 +/- 12.3 years underwent temporary nerve stimulation. Temporary nerve stimulation was successful in eight patients, six of whom were implanted. Of the patients who could be evaluated, three of five had improved at the six-month follow-up visit, particularly in relation to the number of urgency episodes and delay in postponing defecation. All implanted patients had urinary symptoms. Urinary urgency was also improved by stimulation. During temporary nerve stimulation, the maximal squeeze pressure amplitude increased. After implantation, only the duration of maximal squeeze pressure seemed to improve. CONCLUSION: Sacral nerve stimulation can be used in the management of fecal incontinence, particularly in cases of urge fecal incontinence associated with urinary urgency. This study seems to confirm the effect of sacral nerve stimulation on striated sphincter function.

Adult↗
PubMed2001

Effects of polyethylene glycol 4000 on 24-h manometric recordings of left colonic motor activity.

BACKGROUND: It has been shown that low doses of polyethylene glycol (PEG) 4000 are effective in the treatment of chronic constipation. The aim of this study was to describe the effects on colonic motility of oral PEG 4000 treatment and intraluminal instillation of PEG 4000. METHODS: Left colonic and rectosigmoid manometric recordings were performed for 27 h in six constipated patients and in six healthy volunteers. At the end of the recording, bisacodyl and PEG 4000 were instilled into the lumen of the colon. To assess the effects of oral administration of PEG 4000 on colonic motility, manometric recordings were also performed in constipated patients after 4 weeks of treatment with PEG 4000. RESULTS: All patients had significantly more stools during than before PEG treatment. There was no significant difference between the number and the characteristics of high-amplitude propagating contractions (HAPC) or the area under the curve (AUC) before or during treatment with PEG 4000. Intraluminal instillation of PEG induced HAPC in only one patient and in no controls. CONCLUSION: This study shows that PEG 4000 has no effect on left colonic and rectosigmoid motor activity during oral treatment, despite its clinical effectiveness, or after local instillation.

Administration, Oral↗
PubMed2001

Testing life-history pleiotropy in Caenorhabditis elegans.

Much life-history theory assumes that alleles segregating in natural populations pleiotropically affect life-history traits. This assumption, while plausible, has rarely been tested directly. Here we investigate the genetic relationship between two traits often suggested to be connected by pleiotropy: maternal body size and fertility. We carry out a quantitative trait locus (QTL) analysis on two isolates of the free-living nematode Caenorhabditis elegans, and identify two body size and three fertility QTLs. We find that one of the fertility QTLs colocalizes with the two body size QTLs on Chromosome IV. Further analysis, however, shows that these QTLs are genetically separable. Thus, none of the five body size or fertility QTLs identified here shows detectable pleiotropy for the assayed traits. The evolutionary origin of these QTLs, possible candidate loci, and the significance for life-history evolution are discussed.

Animals↗
PubMed2000

Somatic polyploidization and cellular proliferation drive body size evolution in nematodes.

Most of the hypodermis of a rhabditid nematode such as Caenorhabditis elegans is a single syncytium. The size of this syncytium (as measured by body size) has evolved repeatedly in the rhabditid nematodes. Two cellular mechanisms are important in the evolution of body size: changes in the numbers of cells that fuse with the syncytium, and the extent of its acellular growth. Thus nematodes differ from mammals and other invertebrates in which body size evolution is caused by changes in cell number alone. The evolution of acellular syncytial growth in nematodes is also associated with changes in the ploidy of hypodermal nuclei. These nuclei are polyploid as a consequence of iterative rounds of endoreduplication, and this endocycle has evolved repeatedly. The association between acellular growth and endoreduplication is also seen in C. elegans mutations that interrupt transforming growth factor-beta signaling and that result in dwarfism and deficiencies in hypodermal ploidy. The transforming growth factor-beta pathway is a candidate for being involved in nematode body size evolution.

Animals↗
PubMed2000

Results of sphincteroplasty in 86 patients with anal incontinence.

PURPOSE: This study was designed to analyze critically the short-term and long-term outcome of sphincteroplasty and to identify high-risk factors. METHODS: Eighty-six patients with fecal incontinence associated with an ultrasound defect of the external anal sphincter were treated by anal sphincteroplasty. Clinical and physiologic assessment was made before surgery, and clinical evaluation was made three months and an average of 40 months after surgery. RESULTS: The evaluation of 86 patients three months after surgery showed that 42 patients were totally continent (49 percent), 28 were incontinent for gas (33 percent), and 16 still had fecal incontinence (19 percent). Seventy-four patients (86 percent) were contacted 40 months after surgery. Twenty-one patients (28 percent) were totally continent, 17 were incontinent to gas (23 percent), and 36 were incontinent to feces (49 percent). Forty-six percent of patients felt they were clearly improved after surgery. Poor results were associated with an internal anal sphincter defect. CONCLUSIONS: Our study suggests that in the long term, one-third of patients are totally continent after sphincteroplasty. One-half of patients are satisfied, but only if their incontinence to feces has totally disappeared. Results of sphincteroplasty deteriorate with time. One factor in poor prognosis is the presence of an associated defect of the internal anal sphincter.

Adult↗
PubMed2000

[Evoked mechanical and electrical anal sphincter responses after cortical and lumbar magnetic stimulation].

In 13 healthy volunteers we recorded electrical and mechanical anal sphincter (AS) evoked responses. Electrical responses were obtained with surface electrodes, and mechanical responses by anal manometry; all responses were compared with those of anterior tibialis. Mechanical evoked responses' latency and amplitude were calculated. The mean total conduction time of the electrical responses was 26.07 ms at rest and 23.31 ms with mild contraction (p < 0.003). After lumbar magnetic stimulations, because of stimulation artefact, electrical responses couldn't be correctly measured. The mean central conduction time calculated with mechanical responses was 21.44 ms at rest and 18.81 ms with mild contraction (p < 0.003). The mean central conduction time to the anterior tibialis was shorter (14.38 ms; p < 0.003). Evoked mechanical responses', amplitudes were respectively 128.2 cm H2O (cortical stimulations at rest), 138.8 cm H2O (cortical stimulations with mild contraction) and 133.1 cm H2O (lumbar stimulations at rest) (NS). Evoked mechanical responses amplitudes were correlated with the AS maximal voluntary contraction amplitude (p < 10(-4)). Mechanical motor evoked responses after cortical and lumbar magnetic stimulations can be recorded and quantified. In anorectal disorders, this technique could be of major interest for the diagnosis of neurologic lesions versus behavioural problems.

Adult↗
PubMed2000

Manometric assessment of an artificial bowel sphincter.

BACKGROUND: This study investigated the relationship between functional clinical results after artificial bowel sphincter implantation and manometric assessment in 12 consecutive patients. METHODS: A postoperative manometric study was performed in 12 patients, including measurement of resting and squeeze pressures, opening characteristics and pressure during straining. The relationship between postoperative findings, clinical outcome and preoperative manometric data was investigated. Anal pressure after rectal distension with a closed cuff was studied in seven patients. Results were expressed as mean(s.d.). RESULTS: Continence for solid stool was achieved in all 12 patients. Five patients remained incontinent for gas. Anal resting pressure was 108(22) cmH2O; there was no difference between continent and incontinent patients. Rectal distension induced anal relaxation in six of seven patients. Total duration of cuff opening was 113(8) s with an amplitude of 60(22) per cent; residual pressure was correlated with the preoperative resting pressure. The total duration of the opening phase in patients with defaecation difficulties (47(24) (range 0-65) s) was shorter than that in patients without defaecation difficulties (178(78) (range 100-320) s) (P = 0.0022). CONCLUSION: Postoperative defaecation difficulties after implantation of an artificial bowel sphincter are related to a short duration of opening of the cuff. The anal sphincter played a role in postoperative resting anal pressures and allowed relaxation even if the cuff was closed.

Adult↗
PubMed2000

Prolonged stationary colonic motility recording in seven patients with severe constipation secondary to antidepressants.

The aim of this study was to determine whether the colonic motor profile of seven patients with constipation secondary to antidepressants differed from the motility of seven patients with idiopathic constipation and seven healthy volunteers. All constipated patients had very severe constipation. Colonic manometric recordings were performed for 24 h. The number of high amplitude propagating contractions (HAPC) was lower in the two groups of constipated patients than in controls. No HAPC were observed in 5/7 patients with constipation secondary to antidepressants and in 1/7 patients with idiopathic constipation. The overall area under the curve (AUC) in the left colon was lower in the two constipated patient groups than in controls. AUC increased after a 1000-kcal standard meal given at noon in controls but not in the two groups of constipated patients. In conclusion, in patients with constipation secondary to antidepressants, the overall AUC was as poor as in patients with idiopathic constipation, and no colonic response to eating was observed. Moreover, the number of HAPC was more markedly decreased in patients with constipation secondary to antidepressants than in patients with idiopathic constipation.

Adult↗
PubMed1999

Prevalence of anal incontinence in 409 patients investigated for stress urinary incontinence.

A clinical questionnaire concerning anorectal symptoms and urodynamic tests was used to investigate 409 women consulting for stress urinary incontinence. To compare urodynamic data, patients were divided into three groups of women who had either stress urinary incontinence associated with incontinence for formed and/or liquid stools or with gas incontinence, or isolated stress urinary incontinence. To take in account the patients'age for data interpretation, a Mantel-Haenszel test or covariate analysis was performed. Anal incontinence was reported in 114 (28%) of the 409 women investigated. The prevalence of incontinence for gas only, for liquid, or for solid stools was 18.3, 9.3, and 1%, respectively. The duration of gas incontinence was longer than that of fecal incontinence or stress urinary incontinence. Difficult defecation was more frequently observed in patients with double incontinence than in patients with only stress urinary incontinence, and the difference was significant between patients with gas incontinence and patients with stress urinary incontinence (53% versus 37%, P = 0. 03). There was no difference in the number of bowel movements per week among the three groups of patients. The number of vaginal deliveries was surprisingly lower in patients with fecal incontinence associated with urinary incontinence than in others. There was no urodynamic feature that could distinguish patients with urinary incontinence and patients with double incontinence. This study confirmed the close relationship between anal and stress urinary incontinence. Neurourol. Urodynam. 18:579-590, 1999.

Adolescent↗
PubMed1999

Pudendal neuropathy and severity of incontinence but not presence of an anal sphincter defect may determine the response to biofeedback therapy in fecal incontinence.

PURPOSE: It has been suggested that the severity of fecal incontinence, the presence of pudendal neuropathy, or an external anal sphincter defect does not preclude clinical improvement with biofeedback therapy. A discrepancy, however, is frequently found between subjective improvement and objective results after biofeedback therapy. Our aim was to assess whether severity of fecal incontinence, presence of pudendal neuropathy, or an external anal sphincter defect could influence the results of manometric parameters after biofeedback therapy in patients with fecal incontinence. METHODS: Biofeedback therapy was used to treat 27 patients with fecal incontinence (25 women; mean age, 53; range, 29-74 years), according to a strict protocol. Manometry, pudendal nerve terminal motor latency, and anal ultrasound were performed in all patients before biofeedback therapy. Manometric evaluation of external anal sphincter function was performed after the biofeedback sessions. RESULTS: Eight of 27 patients had a good clinical response to biofeedback, but with no significant difference in their mean amplitude and duration of squeeze pressure before and after biofeedback. There was no relationship between the clinical results of biofeedback therapy and the initial severity of fecal incontinence, pudendal neuropathy, or external sphincter defect. Patients with severe incontinence (incontinence to solids) and pudendal neuropathy failed to improve the amplitude and duration of their maximum voluntary contraction after biofeedback therapy. Patients with mild fecal incontinence (incontinence to flatus, liquids, or both) (P<0.04), without pudendal neuropathy (P<0.02), or with (P<0.05) and without (P<0.05) external sphincter defect improved their external anal sphincter function after biofeedback therapy. CONCLUSION: In patients with fecal incontinence, the severity of symptoms and pudendal neuropathy should be considered as two factors of poor prognosis of favorable manometric results after biofeedback therapy. Improvement, on the other hand, may be expected after biofeedback therapy despite an external anal sphincter defect.

Anal Canal↗
PubMed1999

Results of pudendal nerve neurolysis-transposition in twelve patients suffering from pudendal neuralgia.

PURPOSE: Pudendal neuralgia caused by nerve compression may be improved by surgical decompression of the pudendal nerve. This study was undertaken to determine if clinical symptoms, electrophysiological investigations, and the efficacy of preoperative pudendal nerve blocks could be used to predict the efficacy of surgery. METHODS: Twelve consecutive patients complaining of anal pain, genital pain, or both, exacerbated in the sitting position and unsuccessfully treated by analgesic drugs before referral were studied. In these 12 patients decompression of the pudendal nerve was performed after unsuccessful CT-guided injection of corticosteroids in the pudendal nerve at the ischial spine or after pain relapse following successful injections. Nineteen nerves were decompressed by surgery, and the compressed area was located between the sacrospinal and sacrotuberal ligaments for 18 nerves. RESULTS: Three months after surgery, four patients were totally relieved, and three were only partially improved. After 21 months of follow-up, three patients were cured, one was slightly improved, and eight remained in pain. In the three patients cured by surgery, pain completely disappeared for at least two weeks after a nerve block repeated twice before surgery, whereas pain relief was observed in only one of the nine other patients (P = 0.018). None of the three patients cured by surgery were being treated for depression, whereas six of the nine remaining patients were receiving antidepressants or were followed by a psychiatrist (P = 0.09). Results of surgery did not depend on other preoperative clinical or electrophysiological data. CONCLUSIONS: This preliminary study suggests that complete disappearance of pain for at least two weeks after a nerve block repeated twice before surgery may be the best criterion to predict success. Based on this criterion, surgery would have been performed in four patients in this study, of whom three would have been cured.

Aged↗