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Biomedical subjects

A Weil

Publications and source records attributed to A Weil.

At least 19 recordsLinked to original sources
PubMed2006

Absence of a food effect with a 145 mg nanoparticle fenofibrate tablet formulation.

OBJECTIVES: The present study was conducted to assess the effect of food on the bioavailability of fenofibric acid from a new tablet formulation containing fenofibrate nanoparticles. METHODS: In this 3-way crossover study, 45 subjects received in a random order one 145 mg fenofibrate tablet under high-fat fed (HFF), low-fat fed (LFF) or fasting (reference) conditions. Plasma concentrations of fenofibric acid were determined up to 120 hours post-dose. Comparisons were made between test (HFF and LFF) and reference conditions (fasting). RESULTS: Very close values of pharmacokinetic parameters were obtained following the three diffiferent regimens. The 90% confidence intervals (CI) for the ratio of geometric means of HIFF versus fasting condition were (1.018-1.088) for AUCinfinity, (1.020-1.090) for AUCt and (0.963-1.054) for Cmax with point estimate:s of 1.052, 1.054 and 1.007, respectively. The 90% CI for the geometric means of LFF versus fasting condition were (0.978-1.046) for AUGinfinity, (0.981-1.047) for AUCt and (0.964-1.055) for Cmax with point estimates of 1.012, 1.013 and 1.009, respectively. They all fall within the required limits for bioequivalence (0.80-1.25). A slightly prolonged tmax was observed following HFF conditions (4.3 +/- 1.9 hours, versus 3.6 +/- 1.2 hours and 2.3 +/- 0.7 hours under LFF and fasting conditions, respectively), without any effect on mean Cmax. CONCLUSION: The peak and overall exposures from the new 145 mg fenofibrate tablet were not affected by food. Therefore, this new fenofibrate tablet may be taken without regard to the timing of meals.

Adolescent↗
PubMed2005

Transgenic mice over-expressing human beta-amyloid have functional nicotinic alpha 7 receptors.

A potentially major factor in the development of Alzheimer's disease is the enhanced production of soluble beta-amyloid peptide fragments amyloid beta peptide(1-40) and amyloid beta peptide(1-42). These amyloid peptides are generated by cleavage of the amyloid-precursor protein and aggregate spontaneously to form amyloid plaques, which are a classical pathological hallmark in Alzheimer's disease. Although the precise mechanisms are unknown, it is widely believed that amyloid peptides initiate the degenerative process, resulting in subsequent cognitive decline. One interaction of amyloid beta peptide that may contribute to an impairment of cognition is its high affinity binding to the alpha 7 nicotinic receptor; a receptor shown to be important for cognition in a number of studies. There is some controversy, however, whether amyloid beta peptide inhibits or activates this receptor. We have cloned and stably expressed the human alpha 7 receptor and investigated its interaction with amyloid beta peptide using patch clamp electrophysiology. Human alpha 7 was activated in a concentration-dependent fashion by nicotine, acetylcholine and choline and potently inhibited by methyllycaconitine citrate. The responses were inwardly rectifying and exhibited rapid activation, desensitization and deactivation. Amyloid beta peptide(1-42) antagonized human alpha7 responses in a partially reversible fashion; no agonist effects of amyloid beta peptide(1-42) were detected. A similar inhibition of mouse alpha 7 was also observed. In addition, we have assessed the function of native alpha 7 receptors in hippocampal slices prepared from transgenic mice that over-express human amyloid. Despite this clear inhibition of recombinant receptors, hippocampal GABAergic interneurones in slices from beta-amyloid over-expressing mice still possess alpha 7 receptor-mediated currents.

Amyloid beta-Peptides↗
PubMed2004

Sonographic detection of fluid collections and postoperative morbidity following Cesarean section and hysterectomy.

OBJECTIVES: To evaluate the clinical significance of sonographically detected fluid collections following Cesarean section and hysterectomy, and to identify risk factors associated with their formation. METHODS: This was a prospective study including 280 women, 145 of whom had undergone a Cesarean section and 135 of whom had undergone abdominal or vaginal hysterectomy. Ultrasound examinations were carried out on all women on day 4 after surgery to assess the presence of abdominal wall or pelvic fluid collections. The sonographers were unaware of the clinical course before the examination and were not involved in any clinical decision-making. Ultrasound findings were correlated with clinical data and postoperative morbidity. RESULTS: A fluid collection was found in 69 (48%) women after Cesarean section, and in 59 (44%) women who had undergone hysterectomy. No risk factors for the development of fluid collections after Cesarean section or hysterectomy were identified. The risk of developing febrile morbidity was not related to the presence, location or size of fluid collections. CONCLUSIONS: Postoperative fluid collections are common after Cesarean section and hysterectomy. As fluid collections detected by sonography were not associated with postoperative morbidity, this finding is unlikely to be useful in the workup for postoperative fever.

Abdominal Wall↗
PubMed2003

Intraobserver and interobserver agreement in the diagnosis of anal sphincter tears by postpartum endosonography.

OBJECTIVE: To evaluate intraobserver and interobserver agreement in the diagnosis of anal sphincter tears by endosonography when performed immediately postpartum by resident obstetricians. METHODS: Fifty-four primiparous women who delivered vaginally and had no anal sphincter tears (third- or fourth-degree perineal tears) diagnosed clinically were recruited. Four observers assessed photographic prints and video recordings of anal endosonography performed before the suture of the perineum. We calculated the intra- and interobserver agreement and the kappa coefficient to quantify the reliability of the diagnosis of clinically occult sphincter tears. RESULTS: The observers described sphincter tears in 13-28% of the prints, and in 7-32% of the video recordings. Intraobserver agreement was rated as substantial for prints (kappa, 0.63), and moderate for video recordings (kappa, 0.48). The interobserver agreement was fair for prints (kappa, 0.34) and moderate for video recordings (kappa, 0.42). CONCLUSION: Endosonography performed immediately postpartum to diagnose anal sphincter tears is of moderate reliability.

Anal Canal↗
PubMed2002

A rare complication with TVT: vaginal protrusion of the tape.

The authors report a rare postoperative complication of TVT. A 38-year-old woman, suffering from genuine stress incontinence, presented 3 weeks after surgery with a 1 cm protrusion of the TVT across the median vaginal scar. A fastening point on the tape and covering it with the vaginal skin was unsuccessful. Three weeks later, we found a 5 mm protrusion of the tape. At this time we decided to resect the protruding fibers but without interrupting the tape. Regular clinical checks showed good local cicatrization, and 4 weeks later the vaginal epithelium covered the tape completely and the patient no longer suffered from genuine stress incontinence.

Adult↗
PubMed2001

Integrated medicine.

Explore the source record for details and available documents.

Complementary Therapies↗
PubMed2001

Prevalence of anal incontinence and other anorectal symptoms in women.

We studied the prevalence of anal incontinence and other anorectal symptoms in women and evaluated the proportion of those who had sought medical help. A structured questionnaire was distributed to 1228 women attending the obstetrics and gynecology outpatient clinics (general, antenatal, urogynecology) of our university hospital. We also screened an additional sample of 984 women, representative of the general population aged 35-74. The prevalence of anal incontinence was 5.6% in the general outpatient clinic, 6.7% in the antenatal clinic, 15.9% in the urogynecology clinic and 4.4% in the general population. Only 20% of women affected by anal incontinence from the general outpatient clinic had reported their symptoms to a medical practitioner. Anal incontinence affects many women, but only a minority seek help. Obstetriciangynecologists should systematically inquire about the presence of this symptom.

Adult↗
PubMed2001

Does a second delivery increase the risk of anal incontinence?

OBJECTIVE: To evaluate the prevalence of anal incontinence and anal sphincter defects after a first vaginal delivery and assess the effect of a second delivery. DESIGN: Prospective cohort study using postal questionnaires assessing incontinence to flatus and stools at three and thirty months postnatally and anal endosonography at three months following delivery. SETTING: Recruitment was from the antenatal clinic at the University Hospitals of Geneva, Switzerland. POPULATION: One hundred women with a vaginal delivery of their first child. MAIN OUTCOME MEASURES: Prevalence of anal incontinence and anal sphincter defects. RESULTS: Anal incontinence was reported by 16/92 (17%) of women at three months after delivery and by 11/77 (14%) at 30 months. At that time, 5/54 (9%) with no further delivery reported incontinence, compared with 6/ 23 (26%) of those who had had another delivery (RR 2.8, 95% CI 1.0-8.3). Anal sphincter defects were diagnosed by endosonography in 46/87 (53%) women and were associated with reported incontinence at both three months (RR 1.9; 95% CI 1.4-2.6) and 30 months (RR 1.9: 95% CI 1.3-2.8) after delivery. The prevalence of anal incontinence at 30 months was highest (5/13, 39%) among those in whom a sphincter defect was diagnosed by endosonography after their first delivery and with a second delivery. CONCLUSION: Anal incontinence after childbirth is associated with defects of the anal sphincter diagnosed by endosonography. Subsequent deliveries increase the risk of incontinence, particularly among women with a sphincter defect diagnosed after the first delivery.

Adult↗
PubMed2001

The future of transgenic plants in developing countries.

Whatever their own policies may be, developing countries will inevitably be affected by the development of genetically-modified organisms in industrialized countries. While maintaining a cautious attitude, most of these countries wish to keep their options open, thus protecting themselves from the risk of being deprived of future technologies that might allow them to achieve self-sufficiency in food production, to resolve certain problems confronting their most vulnerable populations and to preserve the international competitiveness of their products. Companies should see that it is in their interest to help these countries implement their own policies, notably through an open attitude to industrial property. If the value of genetic engineering is thus confirmed, then it perhaps in this manner that GMOs will earn the legitimacy required to make them acceptable to the people of Northern countries where the majority of solvent markets are located.

Agriculture↗
PubMed2000

Correlations in fossil extinction and origination rates through geological time.

Recent analyses have suggested that extinction and origination rates exhibit long-range correlations, implying that the fossil record may be controlled by self-organized criticality or other scale-free internal dynamics of the biosphere. Here we directly test for correlations in the fossil record by calculating the autocorrelation of extinction [corrected] and origination rates through time. Our results show that extinction rates are uncorrelated beyond the average duration of a stratigraphic interval. Thus, they lack the long-range correlations predicted by the self-organized criticality hypothesis. In contrast, origination rates show strong autocorrelations due to long-term trends. After detrending, origination rates generally show weak positive correlations at lags of 5-10 million years (Myr) and weak negative correlations at lags of 10-30 Myr, consistent with aperiodic oscillations around their long-term trends. We hypothesize that origination rates are more correlated than extinction rates because originations of new taxa create new ecological niches and new evolutionary pathways for reaching them, thus creating conditions that favour further diversification.

Animals↗
PubMed2000

Delayed biological recovery from extinctions throughout the fossil record.

How quickly does biodiversity rebound after extinctions? Palaeobiologists have examined the temporal, taxonomic and geographic patterns of recovery following individual mass extinctions in detail, but have not analysed recoveries from extinctions throughout the fossil record as a whole. Here, we measure how fast biodiversity rebounds after extinctions in general, rather than after individual mass extinctions, by calculating the cross-correlation between extinction and origination rates across the entire Phanerozoic marine fossil record. Our results show that extinction rates are not significantly correlated with contemporaneous origination rates, but instead are correlated with origination rates roughly 10 million years later. This lagged correlation persists when we remove the 'Big Five' major mass extinctions, indicating that recovery times following mass extinctions and background extinctions are similar. Our results suggest that there are intrinsic limits to how quickly global biodiversity can recover after extinction events, regardless of their magnitude. They also imply that today's anthropogenic extinctions will diminish biodiversity for millions of years to come.

Animals↗
PubMed2000

Diagnosis of anal sphincter tears by postpartum endosonography to predict fecal incontinence.

OBJECTIVE: To determine whether anal endosonography immediately after vaginal delivery can predict subsequent fecal incontinence. METHODS: We studied nulliparas who delivered vaginally and had no anal sphincter tears (third- or fourth-degree perineal tears) diagnosed clinically by endosonography before any suture of the perineum. The sonographer was unaware of delivery details and the obstetrician and the women were not informed of endosonography results. Therefore, the suture of the perineum and the outcomes were not influenced by sonographer's diagnoses. Three months after delivery, we assessed fecal incontinence by self-administered questionnaires. RESULTS: Clinically undetected tears of the anal sphincter were diagnosed by anal endosonography in 42 of 150 women (28%). The external anal sphincter alone was involved in 30 women (20%), the internal anal sphincter alone in two (1.3%), and both in ten (7%). The postal questionnaire was returned by 144 women. Incontinence was reported by 22 (15%, 95% confidence interval [CI] 10%, 22%), consisting mainly of incontinence to flatus only (16 of 22, 73%, 95% CI 50%, 89%). Clinically undetected anal sphincter tears diagnosed by endosonography were associated with incontinence 3 months after delivery (odds ratio [OR] 8.8; 95% CI 2.9, 26.5). The sensitivity of anal endosonography was 68% (95% CI 49%, 88%) and the positive predictive value 37% (95% CI 22%, 51%). CONCLUSION: Anal endosonography immediately after vaginal delivery allows diagnosis of clinically undetected anal sphincter tears that might be associated with subsequent fecal incontinence.

Adult↗
PubMed2000

CA125 production by the peritoneum: in-vitro and in-vivo studies.

The source of CA125 synthesis is still debated. Endometrial, peritoneal, ovarian and amniotic cells have been demonstrated to produce and secrete CA125. Different studies show that the peritoneum is a source of CA125. The present study aimed at investigating in vivo and in vitro the peritoneal contribution to circulating CA125. Cultures of uterine peritoneum, abdominal peritoneum and myometrium explants were performed and CA125 measured in the culture medium. To modulate the potential production of CA125, the explants were cultured with or without cycloheximide, bacterial lipopolysaccharide (LPS) or ascitic fluid. In a prospective study, we compared a group of patients after abdominal surgery (n = 19; nine men, 10 women) with a group after extra-abdominal surgery (n = 21; 11 men, 10 women), in order to detect a postoperative increase of serum CA125. De-novo synthesis of CA125 could not be demonstrated in the cultures of uterine and abdominal peritoneum and in myometrium, but CA125 concentrations were detectable in the culture medium without being modulated by cycloheximide, LPS or ascitic fluid. After peritoneal surgery, the proportion of patients with increased serum CA125 was significantly higher (P < 0.03) after abdominal surgery as compared with extra-abdominal surgery. This is considered as indirect evidence for in-vivo production of CA125 by the peritoneum.

Abdomen↗
PubMed2000

Anal incontinence in women with third or fourth degree perineal tears and subsequent vaginal deliveries.

We contacted 208 women 13 years after they suffered an obstetrical anal sphincter tear in order to estimate the effect of subsequent vaginal deliveries on anal continence. Among the 177 eligible responders, 129 sustained a partial or complete 3rd degree and 48 a 4th degree tear; 114 women had subsequent vaginal deliveries. Anal incontinence was more common in women with 4th (25.0%) than with 3rd degree tears (11.5%, p = 0.049). Subsequent vaginal deliveries were associated with a higher prevalence of severe incontinence in women with 4th degree tears (p = 0.023). No aggravation or increase in prevalence of incontinence was observed in women with 3rd degree tears. These results suggest that in a subsequent pregnancy, careful evaluation is necessary and an abdominal delivery may be advisable for women with previous major sphincter trauma.

Adult↗
PubMed1998

Quantitative imaging of TATA-binding protein in living yeast cells.

We describe the quantitative monitoring of TATA-binding protein (TBP) localization and expression in living Saccharomyces cerevisiae cells. We replaced the endogenous TBP with a green fluorescent protein (GFP) x TBP fusion, which was imaged quantitatively by laser scanning confocal microscopy (LSCM). When GFP x TBP expression was altered by using various promoters, the levels measured by LSCM correlated well with the levels determined by immunoblot of whole cell extract protein. These results show that GFP x TBP imaging not only offers a method of measurement equivalent to a more conventional technique but also provides real-time quantitation in living cells and subcellular localization information. Time-lapse confocal imaging of GFP x TBP in mitotic yeast cells revealed that it remains localized to the nucleus and displays an asymmetric distribution (1:0.7) between mother and daughter cells. Based on this and data from a mutant which underexpresses GFP x TBP, we suggest that intracellular levels of TBP are near rate-limiting for growth and viability.

Cell Nucleus↗
PubMed1998

[The effect of bile secretion on the pharmacokinetics of a theophylline sustained-release preparation].

Bile excretion changes the physiological milieu of the duodenum, possibly resulting in enhanced absorption of a drug due to increased solubilisation. This possible influence of bile salts following stimulation of gallbladder emptying by the release of cholecystokinin on the pharmacokinetics of a sustained release theophylline (CAS 58-55-9) preparation (Bronchoretard) was evaluated in this study. An open, randomised, 3-way crossover study in 12 healthy, non-smoking volunteers was selected to prove or reject this hypothesis. All subjects received 500 mg of the sustained release theophylline formulation under two different cholagogia stimulating test conditions compared with a fasting reference condition. A standard breakfast and i.m. administration of cholecystokinin enabled a reproducible modulation of bile flow: a moderate and extreme contraction of the gallbladder could be induced after a standard breakfast and after i.m. administration of cholecystokinin, respectively. Following a standard breakfast, gallbladder volumes were approximately halved (50.6%) compared to the baseline volume after 79 min. Injection of 0.3 microgram/kg body weight cholecystokinin resulted in fast and complete gallbladder evacuation (94.6%) 36 min after the application of this cholagogue stimulus. Gallbladder volumes remained more or less constant under fasting conditions. This manipulation of bile flow did not influence concentration/time profiles of the sustained release theophylline preparation compared to the fasting condition. Even almost complete evacuation of the gallbladder after administration of cholecystokinin did not modify the concentration/time profile of theophylline in a relevant way. An unintentional rapid release of theophylline could be excluded for this sustained release formulation for all three treatments, as not a single case of dose dumping was observed. Furthermore, in vitro dissolution investigations using synthetic surfactants can predict neither food effects nor bile influence on the in vivo absorption at least for the sustained release formulation tested.

Adult↗