Recovery of circadian melatonin rhythm after a melatonin holiday in daytime haemodialysis patients on long-term exogenous melatonin.

The effects of exogenous melatonin on sleep diminish after its long-term use in haemodialysis patients. Our aim was to determine whether melatonin levels accumulate after chronic (at least three months) use of exogenous melatonin, 5 mg daily, and whether discontinuation of this treatment improves endogenous melatonin production and improves the circadian sleep-wake rhythm. In this case series, stable haemodialysis patients discontinued their chronic exogenous melatonin usage for seven days and melatonin concentrations in saliva were analysed. The primary endpoint was recovery of a normal circadian melatonin rhythm. Secondary endpoints were the effects on melatonin pharmacokinetics and sleep parameters. At day three after discontinuation the normal circadian melatonin rhythm recovered in the two patients who discontinued the treatment for the full week. They also had an effective maximum trough level of melatonin. Discontinuing melatonin seems to result in recovery of the circadian rhythm, based on achievement of effective melatonin thresholds. Further research is necessary to investigate whether sleep parameters improve after a drug holiday.most appropriate treatment.

Slow-5 dynamic functional connectivity reflects the capacity to sustain cognitive performance during pain.

Some individuals are more distracted by pain during a cognitive task than others, representing poor pain coping. We have characterized individuals as A-type (attention dominates) or P-type (pain dominates) based on how pain interferes with task speed. The ability to optimize behavior during pain may relate to the flexibility in communication at rest between the dorsolateral prefrontal cortex (DLPFC) of the executive control network, and the anterior mid-cingulate cortex (aMCC) of the salience network (SN) - regions involved in cognitive-interference. The aMCC and aIns (SN hub) also signify pain salience; flexible communication at rest between them possibly allowing prioritizing task performance during pain. We tested the hypotheses that pain-induced changes in task performance are related to resting-state dynamic functional connectivity (dFC) between these region pairs (DLPFC-aMCC; aMCC-aIns). We found that 1) pain reduces task consistency/speed in P-type individuals, but enhances performance in A-type individuals, 2) task consistency is related to the FC dynamics within DLPFC-aMCC and aMCC-aIns pairs, 3) brain-behavior relationships are driven by dFC within the slow-5 (0.01-0.027Hz) frequency band, and 4) dFC across the brain decreases at higher frequencies. Our findings point to neural communication dynamics at rest as being associated with prioritizing task performance over pain.

Assessment of data acquisition parameters, and analysis techniques for noise reduction in spinal cord fMRI data.

PURPOSE: The purpose of this work is to characterize the noise in spinal cord functional MRI, assess current methods aimed at reducing noise, and optimize imaging parameters. METHODS: Functional MRI data were acquired at multiple echo times and the contrast-to-noise ratio (CNR) was calculated. Independently, the repetition time was systematically varied with and without parallel imaging, to maximize BOLD sensitivity and minimize type I errors. Noise in the images was characterized by examining the frequency spectrum, and investigating whether autocorrelations exist. The efficacy of several physiological noise reduction methods in both null (no stimuli) and task (thermal pain paradigm) data was also assessed. Finally, our previous normalization methods were extended. RESULTS: The echo time with the highest functional CNR at 3 Tesla is at roughly 75msec. Parallel imaging reduced the variance and the presence of autocorrelations, however the BOLD response in task data was more robust in data acquired without parallel imaging. Model-free based approaches further increased the detection of active voxels in the task data. Finally, inter-subject registration was improved. CONCLUSIONS: Results from this study provide a rigorous characterization of the properties of the noise and assessment of data acquisition and analysis methods for spinal cord and brainstem fMRI.

The current state-of-the-art of spinal cord imaging: methods.

A first-ever spinal cord imaging meeting was sponsored by the International Spinal Research Trust and the Wings for Life Foundation with the aim of identifying the current state-of-the-art of spinal cord imaging, the current greatest challenges, and greatest needs for future development. This meeting was attended by a small group of invited experts spanning all aspects of spinal cord imaging from basic research to clinical practice. The greatest current challenges for spinal cord imaging were identified as arising from the imaging environment itself; difficult imaging environment created by the bone surrounding the spinal canal, physiological motion of the cord and adjacent tissues, and small cross-sectional dimensions of the spinal cord, exacerbated by metallic implants often present in injured patients. Challenges were also identified as a result of a lack of "critical mass" of researchers taking on the development of spinal cord imaging, affecting both the rate of progress in the field, and the demand for equipment and software to manufacturers to produce the necessary tools. Here we define the current state-of-the-art of spinal cord imaging, discuss the underlying theory and challenges, and present the evidence for the current and potential power of these methods. In two review papers (part I and part II), we propose that the challenges can be overcome with advances in methods, improving availability and effectiveness of methods, and linking existing researchers to create the necessary scientific and clinical network to advance the rate of progress and impact of the research.

The current state-of-the-art of spinal cord imaging: applications.

A first-ever spinal cord imaging meeting was sponsored by the International Spinal Research Trust and the Wings for Life Foundation with the aim of identifying the current state-of-the-art of spinal cord imaging, the current greatest challenges, and greatest needs for future development. This meeting was attended by a small group of invited experts spanning all aspects of spinal cord imaging from basic research to clinical practice. The greatest current challenges for spinal cord imaging were identified as arising from the imaging environment itself; difficult imaging environment created by the bone surrounding the spinal canal, physiological motion of the cord and adjacent tissues, and small crosssectional dimensions of the spinal cord, exacerbated by metallic implants often present in injured patients. Challenges were also identified as a result of a lack of "critical mass" of researchers taking on the development of spinal cord imaging, affecting both the rate of progress in the field, and the demand for equipment and software to manufacturers to produce the necessary tools. Here we define the current state-of-the-art of spinal cord imaging, discuss the underlying theory and challenges, and present the evidence for the current and potential power of these methods. In two review papers (part I and part II), we propose that the challenges can be overcome with advances in methods, improving availability and effectiveness of methods, and linking existing researchers to create the necessary scientific and clinical network to advance the rate of progress and impact of the research.

Diffusion tensor imaging in the human spinal cord: development, limitations, and clinical applications.

Diffusion tensor imaging (DTI) is currently the only non-invasive in vivo assessment of white matter tract integrity. Capitalizing on the diffusion properties of water within an axon, DTI enables the visualization of tissue structure at a microscopic scale. Furthermore, measurements of anisotropy and diffusivity enable the detection of subtle details of the effects of injury that cannot be detected using conventional magnetic resonance techniques. Recently, DTI has been applied to the spinal cord, and results have demonstrated it to be a valuable tool for assessing the extent of white matter damage in numerous spinal cord-related conditions including multiple sclerosis, spinal cord injury, amyotrophic lateral sclerosis, myelitis, and spinal cord tumors. The purpose of this review is to discuss the technical limitations of the imaging method within the spinal cord, review possible solutions, and highlight the current uses and the potential clinical application of this technique.

Advanced MR imaging techniques and characterization of residual anatomy.

Advances in technology in recent decades have contributed to rapid developments in non-invasive methods for imaging human anatomy, and advanced imaging methods are now one of the primary tools for clinical diagnosis after neurological trauma or disease. Here we review the current and upcoming capabilities of one of the most rapidly developing methods, magnetic resonance imaging (MRI). The underlying theory is introduced so that the reasons for the strengths, weaknesses, and future expectations of this method, can be explained. Current techniques for imaging anatomical changes, inflammation, and changes in white matter, axonal integrity, blood flow and function, are reviewed. Applications for specific purposes of assessing traumatic injury in the brain or spinal cord, and for multiple-sclerosis are also presented, and are used as examples of how the advanced techniques are being used in practice.

Characteristics and health of Turkey husbandry in ouaké, north-benin.

Sanitary constraints of raising turkey in north-west Benin were studied by using a survey and Haemagglutination Inhibition Test (HIT) to detect antibodies of Newcastle Disease (ND) and Avian Influenza (AI). We tested 85 serums from 7- to 24-month-old turkeys raised in 19 farms. ND prevalence rate was 54% but reactions on four sub-types of AI were negative. Mortality rates varied from 55 to 100% for 0-30 day-old flocks; 30% for 1- to 4-month-old; and 15% for older turkeys. Next to ND, probable causes of mortality are Fowl pox, Gumboro disease, scabies, coccidiosis, histomonosis, capillariosis and colibacillosis. Only one farmer who fed and vaccinated the poults, and provided clean housing for them got a lower mortality rate of 11% in turkeys less than 4-month-old. The question remains why most farmers do not apply these simple practices: are they unaware or are the technologies not profitable?

Nephrectomy elicits impact of age and BMI on renal hemodynamics: lower postdonation reserve capacity in older or overweight kidney donors.

Renal functional reserve could be relevant for the maintenance of renal function after kidney donation. Low-dose dopamine induces renal vasodilation with a rise in glomerular filtration rate (GFR) in healthy subjects and is thought to be a reflection of reserve capacity (RC). Older age and higher body mass index (BMI) may be associated with reduced RC. We therefore investigated RC in 178 consecutive living kidney donors (39% males, age 48 +/- 11 years, BMI 25.5 +/- 4.1). RC was determined as the rise in GFR ((125)I-iothalamate), 4 months before and 2 months after donor nephrectomy. Before donor nephrectomy, GFR was 114 +/- 20 mL/min, with a reduction to 72 +/- 12 mL/min after donor nephrectomy. The dopamine-induced rise in GFR of 11 +/- 10% was reduced to 5 +/- 7% after donor nephrectomy (p < 0.001). Before donor nephrectomy, older age and higher BMI did not affect reserve capacity. After donor nephrectomy, the response of GFR to dopamine independently and negatively correlated with older age and higher BMI. Moreover, postdonation reserve capacity was absent in obese donors. The presence of overweight had more impact on loss of RC in younger donors. In conclusion, donor nephrectomy unmasked an age- and overweight-induced loss of reserve capacity. Younger donors with obesity should be carefully monitored.

Growth inhibition of Monodus subterraneus by free fatty acids.

Monodus subterraneus is a microalga, which is known for its high eicosapentaenoic acid (EPA; 20:5omega3) content. To produce EPA commercially, high volumetric productivities of microalgae are required. These high productivities can be reached in flat panel photobioreactors with small optical paths that have to be operated at high cell densities (>10 g/L). However, at these cell densities a reduction of productivity is observed. This growth inhibition is probably caused by growth inhibitors released by the microalgae, which have been suggested to be fatty acids. Our aim was to investigate if free fatty acids produced by M. subterraneus inhibited growth of this species. Therefore a bioassay was developed and saturated, unsaturated and poly-unsaturated fatty acids occurring in Monodus were tested on their growth inhibiting properties. Growth of M. subterraneus was completely inhibited at a saturated concentration (96 microM) of palmitoleic acid (16:1omega7). But, the saturated fatty acid palmitic acid (16:0) and the mono-saturated oleic acid (18:1omega9) were much stronger inhibitors. Growth was inhibited for 50% already at concentrations of 0.4 microM 16:0 and 3 microM 18:1omega9, respectively. These fatty acids probably cause the growth inhibition in high cell density cultures of M. subterraneus.

Body mass index and glomerular hyperfiltration in renal transplant recipients: cross-sectional analysis and long-term impact.

Obesity is a risk factor for renal graft loss. Higher body mass index (BMI) in native kidneys is associated with glomerular hyperfiltration. Whether higher BMI in renal transplants is associated with hyperfiltration is unknown. We investigated the impact of BMI on renal hemodynamics 1 year post-transplant. We analyzed glomerular filtration rate (GFR, (125)I-iothalamate) and effective renal plasma flow (ERPF, (131)I-hippurate) in 838 kidney transplants. Data were analyzed for all patients and for the subpopulation without diabetes. Long-term impact of BMI and renal hemodynamics were explored by Cox-regression. With higher BMI GFR and filtration fraction (FF) increased significantly. Multivariate analysis supported impact of BMI on GFR (adjusted r(2) of the model 0.275) and FF (adjusted r(2) of the model 0.158). This association was not explained by diabetes mellitus. On Cox-regression analysis, lower GFR and higher FF were independent determinants of overall graft loss and graft loss by patient mortality. Lower GFR and higher BMI were determinants of death-censored graft loss, with borderline contribution of higher FF. In renal transplants higher BMI is independently associated with higher GFR and FF one year posttransplant, suggesting glomerular hyperfiltration with altered afferent-efferent balance. Mechanisms underlying the long-term prognostic impact of hyperfiltration deserve further exploration.

Obesity and renal hemodynamics.

Obesity is a risk factor for renal damage in native kidney disease and in renal transplant recipients. Obesity is associated with several renal risk factors such as hypertension and diabetes that may convey renal risk, but obesity is also associated with an unfavorable renal hemodynamic profile independent of these factors, and that may exert effects on renal damage as well. In animal models of obesity-associated renal damage, micro-puncture studies showed glomerular hypertension and hyperfiltration. In humans an elevated glomerular filtration rate has been demonstrated in several studies, sometimes associated with hyperperfusion as well, independent of blood pressure or the presence of diabetes. An elevated filtration fraction was found in several studies, consistent with glomerular hypertension. This renal hemodynamic profile resembles the hyperfiltration pattern in diabetes and is therefore assumed to be a pathogenetic factor in renal damage. Of note, the association between body mass index and renal hemodynamics is not limited to overt obesity or overweight, but is also present across the normal range, without a particular threshold. Multiple factors are assumed to contribute to these renal hemodynamic alterations, such as insulin resistance, the renin-angiotensin system and the tubulo-glomerular responses to increased proximal sodium reabsorption, and possibly also inappropriate activity of the sympathetic nervous system and increased leptin levels. Obesity has a high world-wide prevalence. On a population-basis, therefore, its contribution to long-term renal risk may be considerable, especially as it is usually clustered with risk factors like hypertension and insulin resistance. In short-term studies the renal hemodynamic alterations in obesity and the associated proteinuria were reversible by weight loss, and renin-angiotensin system-blockade, respectively. These interventions are therefore likely to have the potential to limit the renal risks of obesity.

Efficacy of desmopressin in patients with multiple sclerosis suffering from bladder dysfunction: a meta-analysis.

OBJECTIVES: The current review evaluates the safety and efficacy of desmopressin in patients with multiple sclerosis (MS) who suffer from both daytime and nocturnal voiding frequency and from incontinence. MATERIALS AND METHODS: A literature search was carried out looking for studies published between 1990 and 2003 which evaluated desmopressin in MS patients with bladder dysfunction. RESULTS: The grand total mean effect sizes show the following estimates of clinical relevant differences: desmopressin has a moderate effect on the number of voids during the day or during the night over a period of 6 h after taking the drug. A large effect associated with the use of desmopressin was detected by the mean difference in urine volume (ml) in 6 h. A small effect was detected in the mean 24-h urine volume. Serum sodium levels were combined with plasma osmolality in some studies and were found to be not significantly affected by desmopressin treatment.

Characteristics of peri-urban dairy herds of Bobo-Dioulasso (Burkina Faso).

Peri-urban dairy cattle farms within 50 km of Bobo-Dioulasso were studied to assess herd type, disease incidence, management, feeding and breeding strategy. Out of 417 cattle farmers, 42% had dairy objectives and were studied. Among these peri-urban dairy farmers, 60% were settled, 36% semi-settled, and 4% transhumant. In total, they held 4558 dairy cows, of which 32% lactated during the study. The prevalence of mastitis (55%) increased (p<0.05) with herd size. Advanced strategies for supplementary feeding and breeding were most frequent in small herds (<30 cattle). None of the large herds (>60 cattle) had advanced breeding strategies. Bulls and cows were culled at younger ages in herds with better breeding strategy. Overall, this resulted in higher individual milk offtake in small herds (2.46 L/day) compared with large herds (1.25 L/day). Pure breeds were rarely used, and the presence of Bos taurus baoulé naturally selected for trypanotolerance was low. The prevalence of trypanosomosis (40%) in herds dominated by Bos indicus zebu and Méré (Zebu x Baoulé) is an argument for maintenance of biodiversity and selection of Baoulé for milk production.

Integrated reactor concepts for the enzymatic kinetic synthesis of cephalexin.

Integrated process concepts for enzymatic cephalexin synthesis were investigated by our group, and this article focuses on the integration of reactions and product removal during the reactions. The last step in cephalexin production is the enzymatic kinetic coupling of activated phenylglycine (phenylglycine amide or phenylglycine methyl ester) and 7-aminodeacetoxycephalosporanic acid (7-ADCA). The traditional production of 7-ADCA takes place via a chemical ring expansion step and an enzymatic hydrolysis step starting from penicillin G. However, 7-ADCA can also be produced by the enzymatic hydrolysis of adipyl-7-ADCA. In this work, this reaction was combined with the enzymatic synthesis reaction and performed simultaneously (i.e., one-pot synthesis). Furthermore, in situ product removal by adsorption and complexation were investigated as means of preventing enzymatic hydrolysis of cephalexin. We found that adipyl-7-ADCA hydrolysis and cephalexin synthesis could be performed simultaneously. The maximum yield on conversion (reaction) of the combined process was very similar to the yield of the separate processes performed under the same reaction conditions with the enzyme concentrations adjusted correctly. This implied that the number of reaction steps in the cephalexin process could be reduced significantly. The removal of cephalexin by adsorption was not specific enough to be applied in situ. The adsorbents also bound the substrates and therewith caused lower yields. Complexation with beta-naphthol proved to be an effective removal technique; however, it also showed a drawback in that the activity of the cephalexin-synthesizing enzyme was influenced negatively. Complexation with beta-naphthol rendered a 50% higher cephalexin yield and considerably less byproduct formation (reduction of 40%) as compared to cephalexin synthesis only. If adipyl-7-ADCA hydrolysis and cephalexin synthesis were performed simultaneously and in combination with complexation with beta-naphthol, higher cephalexin concentrations also were found. In conclusion, a highly integrated process (two reactions simultaneously combined with in situ product removal) was shown possible, although further optimization is necessary.

Modeling of the enzymatic kinetic synthesis of cephalexin--influence of substrate concentration and temperature.

During enzymatic kinetic synthesis of cephalexin, an activated phenylglycine derivative (phenylglycine amide or phenylglycine methyl ester) is coupled to the nucleus 7-aminodeacetoxycephalosporanic acid (7-ADCA). Simultaneously, hydrolysis of phenylglycine amide and hydrolysis of cephalexin take place. This results in a temporary high-product concentration that is subsequently consumed by the enzyme. To optimize productivity, it is necessary to develop models that predict the course of the reaction. Such models are known from literature but these are only applicable for a limited range of experimental conditions. In this article a model is presented that is valid for a wide range of substrate concentrations (0-490 mM for phenylglycine amide and 0-300 mM for 7-ADCA) and temperatures (273-298 K). The model was built in a systematic way with parameters that were, for an important part, calculated from independent experiments. With the constants used in the model not only the synthesis reaction but also phenylglycine amide hydrolysis and cephalexin hydrolysis could be described accurately. In contrast to the models described in literature, only a limited number (five) of constants was required to describe the reaction at a certain temperature. For the temperature dependency of the constants, the Arrhenius equation was applied, with the constants at 293 K as references. Again, independent experiments were used, which resulted in a model with high statistic reliability for the entire temperature range. Low temperatures were found beneficial for the process because more cephalexin and less phenylglycine is formed. The model was used to optimize the reaction conditions using criteria such as the yield on 7-ADCA or on activated phenylglycine. Depending on the weight of the criteria, either a high initial phenylglycine amide concentration (yield on 7-ADCA) or a high initial 7-ADCA concentration (yield on phenylglycine amide) is beneficial.

Histological and bacteriological evaluation of digital dermatitis in cattle, with special reference to spirochaetes and Campylobacter faecalis.

Tissue samples from the feet of slaughtered cattle exhibiting different stages of digital dermatitis were sectioned and stained with haematoxylin and eosin and silver staining techniques. Three morphological variations of spirochaetes were observed, whereas control samples from feet which were macroscopically negative for digital dermatitis were also negative for spirochaetes. In an immunofluorescence test, Campylobacter faecalis was found to be abundant on superficial wound smears from the classical ulceration of digital dermatitis.

Endourological management of ureteral obstruction after renal transplantation.

PURPOSE: We evaluated endourological treatment of ureteral obstruction after renal transplantation. MATERIALS AND METHODS: Between January 1986 and December 1993, 582 kidney transplantations were performed at our center, and ureteral obstruction was suspected in 31 cases (5.3%). RESULTS: Initial treatment consisted of retrograde placement of an internal stent in 6 patients and percutaneous nephrostomy in 25. Due to upper tract dilatation obstruction could not be diagnosed in 3 patients, and rejection was the cause of decreasing renal function. Obstruction was temporary in 8 of the remaining 28 patients, including 6 in whom a Double-J stent was introduced in a retrograde manner without anesthesia. In the other 2 patients was well as the 20 with definitive obstruction, cannulation of the transplant orifice without anesthesia was unsuccessful and percutaneous nephrostomy drainage was necessary. Even with general anesthesia a guide wire could not be passed along the stricture in a retrograde or antegrade fashion in 7 of the 20 patients with definitive obstruction and open surgery was performed. The remaining 13 patients underwent dilation with (9) or without (4) diathermic incision. All 4 patients treated with dilation only had recurrent obstruction, while 9 treated with dilation and incision had no recurrence after a minimum followup of 27 months (mean 58). CONCLUSIONS: Modern endourological procedures have replaced open reconstructive surgery in the majority of patients with ureteral obstruction after renal transplantation.