Lessons on fruiting body morphogenesis from genomes and transcriptomes of Agaricomycetes.

Fruiting bodies (sporocarps, sporophores or basidiomata) of mushroom-forming fungi (Agaricomycetes) are among the most complex structures produced by fungi. Unlike vegetative hyphae, fruiting bodies grow determinately and follow a genetically encoded developmental program that orchestrates their growth, tissue differentiation and sexual sporulation. In spite of more than a century of research, our understanding of the molecular details of fruiting body morphogenesis is still limited and a general synthesis on the genetics of this complex process is lacking. In this paper, we aim at a comprehensive identification of conserved genes related to fruiting body morphogenesis and distil novel functional hypotheses for functionally poorly characterised ones. As a result of this analysis, we report 921 conserved developmentally expressed gene families, only a few dozens of which have previously been reported to be involved in fruiting body development. Based on literature data, conserved expression patterns and functional annotations, we provide hypotheses on the potential role of these gene families in fruiting body development, yielding the most complete description of molecular processes in fruiting body morphogenesis to date. We discuss genes related to the initiation of fruiting, differentiation, growth, cell surface and cell wall, defence, transcriptional regulation as well as signal transduction. Based on these data we derive a general model of fruiting body development, which includes an early, proliferative phase that is mostly concerned with laying out the mushroom body plan (via cell division and differentiation), and a second phase of growth via cell expansion as well as meiotic events and sporulation. Altogether, our discussions cover 1 480 genes of Coprinopsis cinerea, and their orthologs in Agaricus bisporus, Cyclocybe aegerita, Armillaria ostoyae, Auriculariopsis ampla, Laccaria bicolor, Lentinula edodes, Lentinus tigrinus, Mycena kentingensis, Phanerochaete chrysosporium, Pleurotus ostreatus, and Schizophyllum commune, providing functional hypotheses for ~10 % of genes in the genomes of these species. Although experimental evidence for the role of these genes will need to be established in the future, our data provide a roadmap for guiding functional analyses of fruiting related genes in the Agaricomycetes. We anticipate that the gene compendium presented here, combined with developments in functional genomics approaches will contribute to uncovering the genetic bases of one of the most spectacular multicellular developmental processes in fungi. Citation: Nagy LG, Vonk PJ, Künzler M, Földi C, Virágh M, Ohm RA, Hennicke F, Bálint B, Csernetics Á, Hegedüs B, Hou Z, Liu XB, Nan S, M. Pareek M, Sahu N, Szathmári B, Varga T, Wu W, Yang X, Merényi Z (2023). Lessons on fruiting body morphogenesis from genomes and transcriptomes of Agaricomycetes. Studies in Mycology 104: 1-85. doi: 10.3114/sim.2022.104.01.

Man vs. machine: A meta-analysis on the added value of human support in text-based internet treatments ("e-therapy") for mental disorders.

Guided internet-based treatment is more efficacious than completely unguided or self-guided internet-based treatment, yet within the spectrum of guidance, little is known about the added value of human support compared to more basic forms of guidance. The primary aims of this meta-analysis were: (1) to examine whether human guidance was more efficacious than technological guidance in text-based internet treatments ("e-therapy") for mental disorders, and (2) whether more intensive human guidance outperformed basic forms of human guidance. PsycINFO, PubMed and Web of Science were systematically searched for randomized controlled trials that directly compared various types and degrees of online guidance. Thirty-one studies, totaling 6215 individuals, met inclusion criteria. Results showed that human guidance was slightly more efficacious than technological guidance, both in terms of symptom reduction (g = 0.11; p < .01) and adherence (0.26 < g < 0.29; p's < 0.01). On the spectrum of human support, results were slightly more favorable for regular guidance compared to optional guidance, but only in terms of adherence (OR = 1.89, g = 0.35; p < .05). Higher qualification of online counselors was not associated with efficacy. These findings extend and refine previous reports on guided and unguided online treatments.

The predictive value of drug-induced sleep endoscopy for treatment success with a mandibular advancement device or positional therapy for patients with obstructive sleep apnea.

PURPOSE: As drug-induced sleep endoscopy (DISE) can provide additional diagnostic information on collapse patterns of the upper-airway, it is widely used in patients with obstructive sleep apnea (OSA). Although more controversial, DISE may also predict the success of treatment with a mandibular advancement device (MAD) and/or positional therapy (PT). In 2018, we proposed a prediction model to investigate the predictive value of passive maneuvers during DISE - such as jaw thrust and changes in body position - on upper-airway patency. Based on the outcomes of various studies, we then adjusted our DISE protocol to better mimic the effect of a MAD, PT, or a combination of both. The aim of this study was to verify whether or not our adjustments would increase the value of DISE as a selection tool. METHODS: This single-center retrospective cohort study involved a consecutive series of patients with OSA. Patients were included if a DISE had been performed in supine and non-supine sleeping position and with and without a boil-and-bite MAD in situ between December 2018 and February 2020. The VOTE scoring system was used to evaluate the obstruction at four levels of the upper-airway. RESULTS: Among 94 patients included. the median apnea-hypopnea index (AHI) was 16.2 (events/h). As a temporary MAD during DISE reduced obstruction by 54% and jaw thrust by 57%, both mimicked the effect of the custom-made MADs referred to in the literature, which reduces the AHI by 60%. Head-and-trunk rotation reduced obstruction by 55% and thus mimicked the effect of PT, which is known to reduce the AHI by 50%. CONCLUSION: A jaw thrust, a temporary MAD, and head-and-trunk rotation during DISE all seem to mimic the treatment effects of MAD and PT. These findings may be of added value when choosing OSA treatment. To prove the predictive value of these maneuvers during DISE, a prospective study should be performed.

Standardized framework to report on the role of sleeping position in sleep apnea patients.

PURPOSE: Sleep apnea is a multifactorial illness which can be differentiated in various physiological phenotypes as a result of both anatomical and non-anatomical contributors (e.g., low respiratory arousal threshold, high loop gain). In addition, the frequency and duration of apneas, in the majority of patients with OSA, are influenced by sleeping position. Differences in characteristics between non-positional patients (NPP) and positional patients (PP) suggest another crucial phenotype distinction, a clinical phenotype focusing on the role of sleeping position on sleep apnea. Since this clinical phenotype distinction has therapeutic implications, further research is necessary to better understand the pathophysiology behind this phenotypic trait and to improve management of PP. Therefore, we suggest a standardized framework that emphasizes the role of sleeping position when reporting clinical and research data on sleep apnea. METHODS: We identified 5 key topics whereby a standardized framework to report on the role of sleeping position would be of added value: (1) sleep study data, (2) anatomical, morphological and physiological factors, (3) drug-induced sleep endoscopy (DISE) findings, (4) sleep apnea management, and (5) effectiveness versus efficacy of positional therapy in sleep apnea management. We performed a literature search to identify evidence to describe and support the rationale behind these 5 main recommendations. RESULTS: In this paper, we present the rationale behind this construct and present specific recommendations such as reporting sleep study indices (disease severity) and sleep time spent in various sleeping positions. The same is suggested for DISE findings and effect of treatment. Sleep study indices (disease severity), anatomical, morphological, and physiological factors in sleep apnea patients should be reported separately for PP and NPP. CONCLUSION: Applying these suggestions in future research will improve patient care, assist in better understanding of this dominant phenotype, and will enhance accurate comparisons across studies and future investigations.

Short-term results of upper airway stimulation in obstructive sleep apnoea patients: the Amsterdam experience.

OBJECTIVES: This paper aimed to: retrospectively analyse single-centre results in terms of surgical success, respiratory outcomes and adverse events after short-term follow up in obstructive sleep apnoea patients treated with upper airway stimulation; and evaluate the correlation between pre-operative drug-induced sleep endoscopy findings and surgical success. METHODS: A retrospective descriptive cohort study was conducted, including a consecutive series of obstructive sleep apnoea patients undergoing implantation of an upper airway stimulation system. RESULTS: Forty-four patients were included. The total median Apnoea-Hypopnea Index and oxygen desaturation index significantly decreased from 37.6 to 8.3 events per hour (p < 0.001) and from 37.1 to 15.9 events per hour (p < 0.001), respectively. The surgical success rate was 88.6 per cent, and did not significantly differ between patients with or without complete collapse at the retropalatal level (p = 0.784). The most common therapy-related adverse event reported was (temporary) stimulation-related discomfort. CONCLUSION: Upper airway stimulation is an effective and safe treatment in obstructive sleep apnoea patients with continuous positive airway pressure intolerance or failure. There was no significant difference in surgical outcome between patients with tongue base collapse with or without complete anteroposterior collapse at the level of the palate.

Floppy epiglottis during drug-induced sleep endoscopy: an almost complete resolution by adopting the lateral posture.

PURPOSE: To analyze the presence of a floppy epiglottis (FE) during drug-induced sleep endoscopy in non-apneic snoring patients, non-positional obstructive sleep apnea (OSA) patients (NPP), and position-dependent OSA patients (PP) and to evaluate the impact of maneuvers and body position during drug-induced sleep endoscopy, including jaw thrust and supine and lateral head (and trunk) position. METHODS: Retrospective cohort study. RESULTS: In total, 324 patients were included. In 60 patients (18.5%), a FE was found in supine position: seven non-apneic snoring patients and 53 OSA patients. When performing lateral head rotation only, a FE was present in four patients (NPP, N = 0; PP, N = 4). When patients were tilted to both lateral head and trunk position, a FE was found in only one subject. After applying jaw thrust, a FE was still present in 10 patients. The prevalence of a FE did not differ between NPP and PP. When comparing baseline characteristics between patients with and without a FE in supine position, no significant differences were found. CONCLUSION: A FE appears almost exclusively in supine position. In patients with a FE, positional therapy can be a promising alternative as a standalone treatment, but also as part of combination therapy with for example mandibular advancement devices or less invasive forms of upper airway surgery.

The influence of position-dependency on surgical success in sleep apnea surgery - a systematic review.

PURPOSE: To evaluate the influence of position-dependency on surgical success of upper airway (UA) surgery in obstructive sleep apnea (OSA) patients. METHODS: Systematic review. RESULTS: Two prospective cohort studies and seven retrospective cohort studies were included in this review. Despite the importance of the subject, it remains unclear whether position-dependency is a predictor for surgical success. No differences were found in surgical success rate between non-positional (NPP) and positional (PP) OSA patients undergoing uvulopalatopharyngoplasty/Z-palatoplasty with or without radiofrequent thermotherapy of the tongue, isolated tongue base or multilevel surgery and hypoglossal nerve stimulation. In one study PP undergoing relocation pharyngoplasty had a greater chance of surgical success. In the majority of the remaining studies, surgical success was in favor of NPP. Furthermore, in the vast part of included studies, the effect of UA surgery was suggested to be greater in the lateral position than supine position. CONCLUSION: Although preoperative characteristics in PP (e.g., lower BMI and AHI) seem to be in favor for higher surgical success compared to NPP, it remains unclear whether position-dependency is a predictor for surgical outcome. It is suggested that the largest differences and expected preoperative and postoperative changes occur in non-supine AHI. In PP, the preoperative non-supine AHI is already lower compared to NPP suggesting a lower chance of surgical success in PP.

New-generation positional therapy in patients with positional central sleep apnea.

PURPOSE: To evaluate the effect of a sleep position trainer (SPT) in patients with positional central sleep apnea (PCSA). METHODS: A multicentre cohort study was conducted. Patients with symptomatic PCSA were included. Effectiveness, compliance and quality of life were assessed at 1- and 6-month follow-up. RESULTS: Sixteen patients were included. Median AHI dropped from 23.4/h [12.9-31.2] to 11.5/h [7.2-24.5] (p = 0.044) after 1-month SPT therapy and in patients who continued treatment, median AHI further decreased after 6 months to 9.7/h [3.4-27.6] (p = 0.075). Median percentage of supine sleep decreased significantly from 37.6 [17.2-51.8] to 6.7 [0.7-22.8] (p < 0.001), after 1 month, and to 6.8 [0.7-22.1] (p = 0.001), after 6 months. Mean compliance over 1 and 6 months was 78.6 ± 35.3 and 66.0 ± 33.3%, respectively. Epworth Sleepiness Scale at baseline was 9.5 [3.3-11.8] and did not significantly decrease after 1 month (11.0 [3.0-13.0]) and 6 months (4.0 [3.0-10.5]) follow-up. Functional Outcomes of Sleep Questionnaire remained stable within the first month. However, after 6 months, there was a significant improvement compared to baseline values, 15.9 [11.9-18.4] vs. 17.8 [14.3-19.2]; p = 0.030. CONCLUSION: This is the first study on effects of positional therapy with a new-generation smart device in patients with PCSA after 1 and 6 months of follow-up. Results of this study show that the SPT is effective in reducing AHI and central AI, feasible in PCSA, and is associated with symptomatic improvement. While the working mechanism behind this effect remains speculative, the effect is positive and considerable.

Polysomnography and sleep position, a Heisenberg phenomenon? : A large-scale series.

BACKGROUND: The severity of position-dependent obstructive sleep apnea (POSA) depends on the nonsupine and supine apnea-hypopnea index (AHI) as well as the time spent in supine position. The latter in particular is susceptible to variation. Several small-scale studies suggest that wearing polysomnography (PSG) apparatus leads to an increase in supine sleeping position. OBJECTIVES: The aim of this study was to evaluate the effect of wearing PSG apparatus on sleeping position and on OSA severity. MATERIAL AND METHODS: A large-scale, retrospective study was performed, including a consecutive series of POSA and non-apneic snoring patients who were prescribed positional therapy (Sleep Position Trainer [SPT]). The effect of wearing PSG apparatus on sleeping position was evaluated by comparing body position during the PSG night and inactive (diagnostic) phase of SPT. RESULTS: The mean percentage of total recording time (TRT) in supine position was 43.1% during the PSG night phase compared with 28.6% of TRT during the inactive (diagnostic) phase of SPT; i.e., a significant decrease of 33.6% (p < 0.001). When adjusting the AHI using TRT in different sleeping positions measured with the SPT, the median AHI decreased from 13.3/h (9.0-20.4) to 10.3/h (6.8-16.2); p < 0.001. When using the adjusted AHI, 33% (N = 66) of all patients had a change in OSA severity. CONCLUSIONS: The results of this study indicate that wearing PSG apparatus leads to an increase in the percentage of supine sleeping position causing an overestimation of OSA severity, especially in patients with POSA. This can have significant impact on both clinical and scientific practice.

Drug-induced sleep endoscopy: the effect of different passive maneuvers on the distribution of collapse patterns of the upper airway in obstructive sleep apnea patients.

PURPOSE: To evaluate the effect of different passive maneuvers (lateral head rotation and jaw thrust) during drug-induced sleep endoscopy (DISE) on distribution of collapse patterns at the level of velum, oropharynx, tongue base, and epiglottis (VOTE). METHODS: Retrospective, single-center cohort study. Patients diagnosed with OSA who underwent DISE between August 2016 and February 2017 were included. During DISE procedure lateral head rotation, jaw thrust and a combination of both were applied and scored by VOTE obstruction level. Also, the effect of these maneuvers was analyzed for complete concentric collapse (CCC) versus complete non-concentric collapse (CNCC) subgroups. RESULTS: Two hundred patients were included (161 male (80.5%), mean age 50.1 ± 11.7 years, median AHI 19.2 (11.7, 31.0) events/h). For lateral head rotation, significant improvement in upper airway collapse at all levels was observed, with exception of the level of the oropharynx, where an increase in obstruction was seen. Jaw thrust resulted in a significant decrease of collapse on all four VOTE levels. The CCC group responded similarly to the CNCC group when only one maneuver was applied, but the CCC group showed less improvement when both maneuvers were combined. CONCLUSIONS: This study gives new insights into the changes in distribution of collapse patterns when passive maneuvers are applied during DISE. Jaw thrust and lateral head rotation gave improvement of obstruction mostly in line with previous research. The CNCC and CCC groups responded similarly to application of a single maneuver, but there was a significant difference found when both maneuvers were combined.

Comparison of upper airway collapse patterns and its clinical significance: drug-induced sleep endoscopy in patients without obstructive sleep apnea, positional and non-positional obstructive sleep apnea.

PURPOSE: To compare patient characteristics, upper airway (UA) collapse patterns and treatment outcome in obstructive sleep apnea (OSA) patients, including non-positional OSA patients (NPP) and positional OSA patients (PP), and non-OSA. METHODS: Cohort study of patients screened for OSA in 2012. Polysomnography was performed and UA was evaluated using the VOTE classification during drug-induced sleep endoscopy (DISE). Treatment outcome of MAD and UA surgery was evaluated. RESULTS: Eight hundred sixty patients were included. Higher BMI, larger neck circumference, and greater age were independent significant predictors for OSA. DISE was performed in 543 patients: 119 non-OSA and 424 OSA patients of whom 257 PP and 167 NPP patients. PP were younger, had smaller neck circumference, lower BMI and apnea-hypopnea index (AHI) than NPP. Collapse at velum (p < 0.001) and oropharynx (p < 0.001) significantly increased the odds for having OSA. Tongue base and epiglottis collapse were, on group level, not determinative for OSA or non-OSA. Complete concentric collapse (CCC) was observed less frequently in PP (31.5%) as compared to NPP (46.1%). After UA surgery, OSA often was cured or improved to less severe positional OSA. Lower efficacy of UA surgery was observed in PP as compared to NPP. No differences were observed in MAD treatment outcome. CONCLUSIONS: Current study provides insight in patients screened for OSA: collapse at velum and oropharynx significantly determined presence of OSA and CCC occurred less frequently in PP compared to NPP. In addition, residual positional dependency is common after UA surgery. More trials are needed to gain insight in pathophysiology and treatment outcome.

Towards a prediction model for drug-induced sleep endoscopy as selection tool for oral appliance treatment and positional therapy in obstructive sleep apnea.

PURPOSE: To evaluate the effect of different passive maneuvers on upper airway patency during drug-induced sleep endoscopy (DISE) compared to recent literature on treatment outcomes of positional therapy (PT), oral appliance therapy (OAT), and combined treatment in obstructive sleep apnea (OSA) patients. METHODS: A retrospective, single-center cohort study including a consecutive series of 200 OSA patients. All patients underwent DISE with and without manually performed jaw thrust and lateral head rotation by using the VOTE classification. The effect of these maneuvers were analyzed by using the sum VOTE score comparing non-positional (NPP) and positional OSA patients (PP). RESULTS: Two hundred patients were included (80.5% male) with a mean age of 50.1 ± 11.7 years, a BMI of 27.0 ± 3.1 kg/m2, and a median AHI of 19.2 events per hour. Forty-four percent of the patients were NPP; of the remaining 56%, 34% was diagnosed with supine isolated and 66% with supine predominant POSA. Manually performed jaw thrust showed a reduction of sum VOTE score of 66.7% in all subgroups. The effect of lateral head rotation was a reduction of 33.3% in NPP and supine predominant PP and 50% in supine isolated PP. Combining these maneuvers a reduction of more than 75% was seen in all patients. CONCLUSIONS: The present model leaves room for improvement. The effect of manually performed jaw thrust is greater and the effect of lateral head rotation alone is less than what was expected compared to recent literature on treatment outcome of OAT, PT, and combined treatment.

Bilateral Vestibular Hypofunction: Insights in Etiologies, Clinical Subtypes, and Diagnostics.

OBJECTIVE: To evaluate the different etiologies and clinical subtypes of bilateral vestibular hypofunction (BVH) and the value of diagnostic tools in the diagnostic process of BVH. MATERIALS AND METHODS: A retrospective case review was performed on 154 patients diagnosed with BVH in a tertiary referral center, between 2013 and 2015. Inclusion criteria comprised (1) imbalance and/or oscillopsia during locomotion and (2) summated slow phase velocity of nystagmus of less than 20°/s during bithermal caloric tests. RESULTS: The definite etiology of BVH was determined in 47% of the cases and the probable etiology in 22%. In 31%, the etiology of BVH remained idiopathic. BVH resulted from more than 20 different etiologies. In the idiopathic group, the percentage of migraine was significantly higher compared to the non-idiopathic group (50 versus 11%, p < 0.001). Among all patients, 23.4% were known with autoimmune disorders in their medical history. All four clinical subtypes (recurrent vertigo with BVH, rapidly progressive BVH, slowly progressive BVH, and slowly progressive BVH with ataxia) were found in this population. Slowly progressive BVH with ataxia comprised only 4.5% of the cases. The head impulse test was abnormal in 94% of the cases. The torsion swing test was abnormal in 66%. Bilateral normal hearing to moderate hearing loss was found in 49%. Blood tests did not often contribute to the determination of the etiology of the disease. Abnormal cerebral imaging was found in 21 patients. CONCLUSION: BVH is a heterogeneous condition with various etiologies and clinical characteristics. Migraine seems to play a significant role in idiopathic BVH and autoimmunity could be a modulating factor in the development of BVH. The distribution of etiologies of BVH probably depends on the clinical setting. In the diagnostic process of BVH, the routine use of some blood tests can be reconsidered and a low-threshold use of audiometry and cerebral imaging is advised. The torsion swing test is not the "gold standard" for diagnosing BVH due to its lack of sensitivity. Future diagnostic criteria of BVH should consist of standardized vestibular tests combined with a history that is congruent with the vestibular findings.

[Infectious disease prevention and occupational-disability insurance for medical students]. / Infectiepreventie en arbeidsongeschiktheidsverzekering voor studenten geneeskunde.

OBJECTIVE: To gain insight into the rate of immunization for hepatitis B and the status of infectious-disease prevention among Dutch medical students working in areas where HIV is endemic. Additionally, to provide an overview of the preparedness of medical schools in the Netherlands to collaborate in the development of a collective occupational disability insurance for their students. DESIGN: Literature review and survey. METHOD: A questionnaire was sent to all 8 Dutch medical schools in 2003 and a follow-up telephone interview was conducted in July 2005. The results of this survey were compared with the international scientific literature, which was systematically searched using PubMed, Web of Science and Picarta up to and including March 2005. RESULTS: There was a great deal of international variation in the proven degree of immunization against hepatitis B. Infectious-disease prevention measures for students on rotation in HIV-endemic areas left much to be desired. Occupational-disability insurance for students who started their clinical rotations was described, particularly in the United States, but details on participation and costs were lacking. In 2003 there were considerable differences between medical schools in the Netherlands regarding hepatitis-B immunization. However, in 2005, all schools reported the implementation of a new national hepatitis-B immunization protocol. Compared to 2003, most schools reported higher safety standards for electives in HIV-endemic areas and post-exposure prophylaxis was more frequently made available at no cost. Individual preparation for these electives still occurred infrequently. None of the medical schools were pursuing a policy of providing occupational disability insurance for students from the beginning of their clinical rotations.

A particulate pulse-release system and mathematical description with the Maxwell-Stefan theory.

In this contribution both the development of a multi-particulate delayed release system with release properties dependent on the swelling of an UV crosslinked coating and a mathematical model to describe its release properties are presented. The formulation consists of a water-soluble core coated with a copolymer of methacrylic acid and ethyl acrylate. Incorporating a network of crosslinked pentaerythritol triacrylate decreases the water-solubility of the coating. After immersing the formulation in water the coating will take up water and subsequently swell in such a degree that the diffusion coefficient of water in the coating will increase. This makes the coating permeable to the dissolved components present in the core. The swelling kinetics of the coating are such that the formulation has a pulse-release profile, i.e. a fast release of the contents is obtained after a pre-determined lag-time. Both the coating thickness and the duration of the UV crosslinking time can be used to adjust the lag-time. The experimental results are used to estimate the Maxwell-Stefan diffusion coefficients of water in the coating. The relation between the Maxwell-Stefan diffusion coefficient and the mole fraction of water in the coating differs from results found in the literature. However, the prediction of the release time based on the presented model is in good agreement with the experimental findings.

Fluid bed agglomeration with a narrow droplet size distribution.

In the fluid bed agglomeration processes liquid distribution influences the agglomerate growth. We developed a new nozzle that produces uniform droplets, which allows droplets to be easily controlled in size independently of liquid- and airflow of the nozzle. It was found that the spray rate and the mixing in the spray zone determine the average granule size and that there is linear relation between the number of droplets of which a granule consists and its volume, at the early stage of the process. The nucleation ratio factor introduced in this paper depends on the material properties of binder liquid and powder particles and is a useful parameter to describe the binder liquid efficiency. The decline of the growth rate of granules during the agglomeration process was due to the less sufficient rewetting of granules resulting in less growth. A linear relation was found between tracer mass added to the binder liquid and the granule mass in an early stage of the process. Solubility of the tracer was found not to influence its distribution. The new nozzle proves to be a good tool to study the effect of wetting and growth of granules.

Microdialysis of glucose in subcutaneous adipose tissue up to 3 weeks in healthy volunteers.

OBJECTIVE: To measure possible changes in dialysate glucose concentrations over time, to validate the diffusional model for glucose transport from tissue to the probe, and to evaluate the actual glucose concentration in adipose tissue. RESEARCH DESIGN AND METHODS: Glucose concentrations in the subcutaneous adipose tissue of five healthy subjects (age 25 +/- 2.7 years, BMI 23.2 +/- 2.3 kg/m2 [mean +/- SD]) were measured by the microdialysis technique and compared with blood glucose. We applied microdialysis probes with hollow fibers of various membrane length (10-35 mm), used eight perfusion flow rates (0.5-20 microl/min), and perfused four glucose solutions (0.0, 2.8, 8.3, 11.1 mmol/l). RESULTS: After implantation, a substantial decrease in glucose recovery to the lowest value of 26 +/- 10% of the final plateau value was noted during the first few hours (n = 4). Recovery increased and stabilized after 5-9 days at 84.0 +/- 7.4% of capillary blood glucose when a flow rate of 0.5 microl/min was applied. According to the zero net-flux method, the glucose concentration in equilibrium, Cequi, with the surrounding tissue can be obtained. This concentration also decreases; however, 1 h after recovery, Cequi increases again over 1 or 2 days to a stable value that is not significantly different from the measured capillary blood glucose (P < 0.05). Using various perfusion flow rates and probes (membrane length 10-35 mm), it is shown that diffusion is the rate-limiting process for glucose transport through tissue. CONCLUSIONS: Insertion of the microdialysis probes causes damage to the adipose cells and the vascular bed around the probe. Glucose recovery decreases because of a lower blood supply. In 5-9 days, glucose recovery increases; apparently, this time is needed to repair the microstructure of tissue around the probe. After stabilization of the recovery, no loss of probe permeability, which is due to biocompatibility problems, was seen. The change during the 2 days in equilibrium concentration is probably caused by an inflammation reaction that consumes glucose around the probe. The individual increase in recovery during the 1st days after probe insertion until a stable plateau value is reached (flow rate >0 microl/min) is complicated for short-term clinical glucose measurements in adipose tissue. After stabilization, the mean equilibrium concentration of all subjects was equal to the mean capillary blood glucose concentration. Therefore, we conclude that capillary blood glucose concentration probably is the driving force for diffusion through the capillary wall into the probe and is not some interstitial concentration.

[Elsberg syndrome: acute urinary retention following a viral infection]. / Het syndroom van Elsberg: acute urineretentie na een virale infectie.

In two patients, women, aged 32 and 30 years respectively, acute urinary retention after a viral infection was diagnosed. This is known as the Elsberg syndrome: urinary retention as a result of sacral myeloradiculitis. One of the patients had a blank history, the other suffered from a genital herpes infection. They were catheterised and instructed to perform catheterisation themselves. One was given an indwelling catheter. In the literature the Elsberg syndrome is mentioned relatively often after a genital herpetic infection. The treatment consists in (self)catheterisation. There may be hypesthesia in the sacral dermatomes. There is a strong tendency to recovering of spontaneous micturition in four to ten days.