Laparoscopic Roux-en-Y feeding jejunostomy as a long-term solution for severe feeding problems in children.

Enteral feeding is a common problem in children with gastric emptying disorders. Traditional feeding methods in these patients often show a high rate of complications and maintenance issues. Laparoscopic Roux-en-Y feeding jejunostomy (LRFJ) has been described in a few patients as a minimal invasive option for enteral access in these children. The aim of this study is to evaluate the outcomes of the LRFJ procedure in our tertiary referral center. We conducted a retrospective case-series including all patients, aged 0-18 years old, that underwent a LFRJ procedure between August 2011 and December 2020 for the indication of oral feeding intolerance due to delayed gastric emptying. Outcomes evaluated were complications (short and long term) and parenteral satisfaction. In total, 12 children were identified that underwent LRFJ for the indication of oral feeding intolerance due to delayed gastric emptying. A total of 16 complications were noted in 8/12 patients (67%). Severity classified by Clavien-Dindo were grade I (n = 13), grade II (n = 1), and grade IIIB (n = 2). In 11/12 patients, parents were satisfied with the results. CONCLUSIONS: Although minor complications after LRFJ are common in our patients, this technique is a safe solution in patients with gastric emptying disorders leading to a definitive method of enteral feeding and high parenteral satisfaction. WHAT IS KNOWN: • Traditional tube feeding in children (duodenal, PEG-J-tubes) with severe delayed gastric emptying can be challenging with a high rate of complications and maintenance issues. • Open loop jejunostomy and Roux-en-Y jejunostomy are alternative, permanent methods of feeding but either invasive or are accompanied by severe complications. Little is known in the literature about laparoscopic Roux-en-Y feeding jejunostomy. WHAT IS NEW: • Laparoscopic Roux-en-Y feeding jejunostomy is a permanent, safe and minimal invasive alternative option for enteral feeding in children with severe delayed gastric emptying..

Public Opinion Leadership in Nursing Practice: A Rogerian Concept Analysis.

In the Dutch nursing context, work remains in strengthening the voice of nurses serving as frontline health care providers and board members alike. Conceptual clarity of Public Opinion Leadership (POL) in nursing practice is needed to provide attributes, antecedents and consequences for nurses and nurse leaders so they can contribute in the public debate and policy making processes. Using Rodgers' method of evolutionary concept analysis and the key words "POL," "lobbying" and "public affairs," we searched PubMed (including MEDLINE), CINAHL, PsycINFO and Cochrane Library for articles written in English, published between January 1999 and May 2020, which resulted in a final selection of seven studies. In addition, transcripts of an expert panel discussion regarding POL were analyzed. Attributes of POL are credibility, accessibility, altruism, dynamic networking and sense of systemness. Antecedents are a clinical background, authentic authority, policy and political awareness and strategic skills. The main consequences of POL entail influencing those who are involved in policy making processes, a new generation of public opinion leaders, and the raising of bottom-up political leaders. POL is a relatively new concept for nursing, with increasing interest given the need to ensure quality of care by increasing the use of evidence in clinical practice. POL in nursing practice is defined as the action of influencing public debate regarding policy making processes by maintaining dynamic (social) networks, having a high sense of systemness, and being (clinically) credible, altruistic and accessible to peers and a wide variety of stakeholders.

Closing system-wide yield gaps to increase food production and mitigate GHGs among mixed crop-livestock smallholders in Sub-Saharan Africa.

In this study we estimate yield gaps for mixed crop-livestock smallholder farmers in seven Sub-Saharan African sites covering six countries (Kenya, Tanzania, Uganda, Ethiopia, Senegal and Burkina Faso). We also assess their potential to increase food production and reduce the GHG emission intensity of their products, as a result of closing these yield gaps. We use stochastic frontier analysis to construct separate production frontiers for each site, based on 2012 survey data prepared by the International Livestock Research Institute for the Climate Change, Agriculture and Food Security program. Instead of relying on theoretically optimal yields-a common approach in yield gap assessments-our yield gaps are based on observed differences in technical efficiency among farms within each site. Sizeable yield gaps were estimated to be present in all of the sites. Expressed as potential percentage increases in outputs, the average site-based yield gaps ranged from 28 to 167% for livestock products and from 16 to 209% for crop products. The emission intensities of both livestock and crop products registered substantial falls as a consequence of closing yield gaps. The relationships between farm attributes and technical efficiency were also assessed to help inform policy makers about where best to target capacity building efforts. We found a strong and statistically significant relationship between market participation and performance across most sites. We also identified an efficiency dividend associated with the closer integration of crop and livestock enterprises. Overall, this study reveals that there are large yield gaps and that substantial benefits for food production and environmental performance are possible through closing these gaps, without the need for new technology.

Effect of Structural Relaxation on the Electronic Structure of Graphene on Hexagonal Boron Nitride.

We performed calculations of electronic, optical, and transport properties of graphene on hexagonal boron nitride with realistic moiré patterns. The latter are produced by structural relaxation using a fully atomistic model. This relaxation turns out to be crucially important for electronic properties. We describe experimentally observed features such as additional Dirac points and the "Hofstadter butterfly" structure of energy levels in a magnetic field. We find that the electronic structure is sensitive to many-body renormalization of the local energy gap.

Moiré patterns as a probe of interplanar interactions for graphene on h-BN.

By atomistic modeling of moiré patterns of graphene on a substrate with a small lattice mismatch, we find qualitatively different strain distributions for small and large misorientation angles, corresponding to the commensurate-incommensurate transition recently observed in graphene on hexagonal BN. We find that the ratio of C-N and C-B interactions is the main parameter determining the different bond lengths in the center and edges of the moiré pattern. Agreement with experimental data is obtained only by assuming that the C-B interactions are at least twice weaker than the C-N interactions. The correspondence between the strain distribution in the nanoscale moiré pattern and the potential energy surface at the atomic scale found in our calculations makes the moiré pattern a tool to study details of dispersive forces in van der Waals heterostructures.

New insights in gastroesophageal reflux, esophageal function and gastric emptying in relation to dysphagia before and after anti-reflux surgery in children.

In children with gastroesophageal reflux (GER) disease refractory to pharmacological therapies, anti-reflux surgery (fundoplication) may be a treatment of last resort. The applicability of fundoplication has been hampered by the inability to predict which patient may benefit from surgery and which patient is likely to develop post-operative dysphagia. pH impedance measurement and conventional manometry are unable to predict dysphagia, while the role of gastric emptying remains poorly understood. Recent data suggest that the selection of patients who will benefit from surgery might be enhanced by automated impedance manometry pressure-flow analysis (AIM) analysis, which relates bolus movement and pressure generation within the esophageal lumen.

Increased expression of interleukin-7 in labial salivary glands of patients with primary Sjögren's syndrome correlates with increased inflammation.

OBJECTIVE: To study the expression levels and immunostimulatory capacities of interleukin-7 (IL-7) in primary Sjögren's syndrome. METHODS: Labial salivary gland (LSG) IL-7 expression was determined by immunohistochemistry, using a quantitative scoring system, in 30 patients with sicca syndrome: 15 patients with primary Sjögren's syndrome (SS) and 15 patients with non-SS sicca syndrome. The correlation of IL-7 expression in LSGs with parameters of local and peripheral disease was studied, and serum and salivary IL-7 levels were determined. Additionally, the effects of IL-7 on cytokine production by peripheral blood mononuclear cells (PBMCs) from patients with primary SS were determined in vitro by Luminex multicytokine assay and compared with the effects in control subjects. RESULTS: The expression of IL-7 in LSGs was higher in patients with primary SS compared with that in patients with non-SS sicca syndrome. IL-7 was observed primarily in the vicinity of lymphocytic infiltrates. Salivary IL-7 levels in patients with primary SS were higher than those in control subjects. In all 30 patients with sicca syndrome, IL-7 expression in LSGs correlated with parameters of both local and peripheral disease. Furthermore, IL-7 stimulated T cell-attracting and T cell-differentiating cytokines (monokine induced by interferon-gamma [IFNgamma], IFNgamma-inducible 10-kd protein, IL-12, and IL-15), as well as Th1 (IFNgamma), Th2 (IL-4), Th17 (IL-17A), proinflammatory (tumor necrosis factor alpha and IL-1alpha), and regulatory (IL-10 and IL-13) cytokine production by PBMCs. All of these cytokines were previously shown to be associated with primary SS. The IL-7-induced increase in IL-10 production in patients with primary SS was reduced compared with that in control subjects. CONCLUSION: The correlation between LSG IL-7 expression and (local) disease parameters in primary SS as well as the IL-7-mediated induction of inflammatory cytokines indicate that IL-7 might contribute to the immunopathology of primary SS.

The use of a sound-enabled device to measure pressure during insertion of an epidural catheter in women in labour.

The insertion of an epidural catheter for labour analgesia may be challenging. This observational study compared pressures during insertion of an epidural catheter in pregnant (n = 35) and non-pregnant (n = 10) women, using an acoustic device for locating the epidural space that also records and stores pressure data during the procedure. In both groups, we compared the maximum pressure just before loss of resistance, the pressure in the epidural space and the pressure in the inserted epidural catheter. Maximum pressure just before loss of resistance in the pregnant women was significantly lower compared with the non-pregnant women. Pressures in the epidural space and with the disposable tubing connected to the inserted epidural catheter were greater in pregnant women than in non-pregnant women. The results support the hypothesis that physiological changes in the third trimester of pregnancy are the reason why epidural catheters are more difficult to insert in women in labour.

[A black wound on the lower arm]. / Een zwartgekleurde wond aan de onderarm.

A 19-year-old man presented on the Emergency Room on New Year's Eve with a 2 cm-wide black burn located on his lower arm. Earlier that evening he was hit by a piece of firework. Even though he immediately felt a sharp burning pain, he did not realize the severity of the injury. He presented with numbness in the digiti 4 and 5 and the Wartenberg sign, which are signs of an ulnar nerve injury. An exploration of the ulnar nerve was performed. Extensive burns and gunpowder were seen on the flexor carpi radialis and ulnaris muscle, the fascia and the epineurium of the ulnar nerve. However, the ulnar nerve was intact. A week later a babysitting procedure was performed because of absent intrinsic muscle activity, with an end-to-side anastomosis of the anterior interosseous nerve to the motor branch of the ulnar nerve. Hand physiotherapy was started after the operation.

If it ain't broke don't fix it? Ethics of splinting deformed newborn ears.

Neonatal ear splinting is a proven and safe method to mold deformed ears into a more common shape. Based on our earlier studies, splinting is recommended only before the age of six weeks and preferably within the first week after birth. This can be done by initiating a system in which this intervention is actively proposed to parents. In this paper, we ethically evaluate such a system. By molding perfectly healthy newborn ears, we reach the boundary between treatment and enhancement. A key question is, therefore, whether we could classify neonatal ear splinting as a therapy. On the level of the individual, the advantages outweigh the drawbacks, but on the level of society, it is more complicated. Making ear deformities a part of official national screening programs fails to meet WHO criteria. Moreover, by systematically offering ear molding, professionals may be promoting guilt or fear of missing the opportunity. Additionally, it could affect societal attitudes toward cosmetic deformities. However, if we argue that on the individual level infants may benefit from ear splinting, then active detection of ear deformities allows parents to choose in a timely way from the full range of options, including splinting and a wait-and-see approach. We are inclined to optimally inform parents without setting up a full-blown public health program. The extent to which it is possible to timely offer splints to parents of newborns depends on the infrastructure of health care systems. The key will be for everyone involved, public or commercial, to responsibly educate and facilitate.

Review: Role of herbivores in sustainable agriculture in Sub-Saharan Africa.

The role of herbivorous livestock in supporting the sustainability of the farming systems in which they are found is complex and sometimes conflicting. In Sub-Saharan Africa (SSA), the integration of livestock into farming systems is important for sustainable agriculture as the recycling of nutrients for crop production through returns of animal manure is a central element of the dominant mixed crop-livestock systems. Sustainable agriculture has been widely advocated as the main practical pathway to address the challenge of meeting the food needs of the rapidly growing population in SSA while safeguarding the needs of future generations. The objective of this paper is to review the state of knowledge of the role of herbivores in sustainable intensification of key farming systems in SSA. The pathways to sustainable agriculture in SSA include intensification of production and livelihood diversification. Sustainable agricultural practices in SSA have focused on intensification practices which aim to increase the output : input ratio through increasing use of inputs, introduction of new inputs or use of existing inputs in a new way. Intensification of livestock production can occur through increased and improved fodder availability, genetic production gains, improved crop residue use and better nutrient recycling of manure. Livestock deliver many 'goods' in smallholder farming systems in SSA including improving food and nutrition security, increased recycling of organic matter and nutrients and the associated soil fertility amendments, adding value to crop residues by turning them into nutrient-rich foods, income generation and animal traction. Narratives on livestock 'bads' or negative environmental consequences have been largely shaped by the production conditions in the Global North but livestock production in SSA is a different story. In SSA, livestock are an integral component of mixed farming systems and they play key roles in supporting the livelihoods of much of the rural population. None-the-less, the environmental consequences of livestock production on the continent cannot be ignored. To enhance agricultural sustainability in SSA, the challenge is to optimize livestock's role in the farming systems by maximizing livestock 'goods' while minimizing the 'bads'. This can be through better integration of livestock into the farming systems, efficient nutrient management systems, and provision of necessary policy and institutional support.

Intra- and interrater reliability of the Chicago Classification of achalasia subtypes in pediatric high-resolution esophageal manometry (HRM) recordings.

BACKGROUND: Subtyping achalasia by high-resolution manometry (HRM) is clinically relevant as response to therapy and prognosis have shown to vary accordingly. The aim of this study was to assess inter- and intrarater reliability of diagnosing achalasia and achalasia subtyping in children using the Chicago Classification (CC) V3.0. METHODS: Six observers analyzed 40 pediatric HRM recordings (22 achalasia and 18 non-achalasia) twice by using dedicated analysis software (ManoView 3.0, Given Imaging, Los Angeles, CA, USA). Integrated relaxation pressure (IRP4s), distal contractile integral (DCI), intrabolus pressurization pattern (IBP), and distal latency (DL) were extracted and analyzed hierarchically. Cohen's κ (2 raters) and Fleiss' κ (>2 raters) and the intraclass correlation coefficient (ICC) were used for categorical and ordinal data, respectively. RESULTS: Based on the results of dedicated analysis software only, intra- and interrater reliability was excellent and moderate (κ=0.89 and κ=0.52, respectively) for differentiating achalasia from non-achalasia. For subtyping achalasia, reliability decreased to substantial and fair (κ=0.72 and κ=0.28, respectively). When observers were allowed to change the software-driven diagnosis according to their own interpretation of the manometric patterns, intra- and interrater reliability increased for diagnosing achalasia (κ=0.98 and κ=0.92, respectively) and for subtyping achalasia (κ=0.79 and κ=0.58, respectively). CONCLUSIONS: Intra- and interrater agreement for diagnosing achalasia when using HRM and the CC was very good to excellent when results of automated analysis software were interpreted by experienced observers. More variability was seen when relying solely on the software-driven diagnosis and for subtyping achalasia. Therefore, diagnosing and subtyping achalasia should be performed in pediatric motility centers with significant expertise.

Objectively diagnosing rumination syndrome in children using esophageal pH-impedance and manometry.

BACKGROUND: Rumination syndrome is characterized by recurrent regurgitation of recently ingested food into the mouth. Differentiation with other diagnoses and gastroesophageal reflux disease (GERD) in particular, is difficult. Recently, objective pH-impedance (pH-MII) and manometry criteria were proposed for adults. The aim of this study was to determine diagnostic ambulatory pH-MII and manometry criteria for rumination syndrome in children. METHODS: Clinical data and 24-hour pH-MII and manometry recordings of children with a clinical suspicion of rumination syndrome were reviewed. Recordings were analyzed for retrograde bolus flow extending into the proximal esophagus. Peak gastric and intraesophageal pressures closely related to these events were recorded and checked for a pattern compatible with rumination. Events were classified into primary, secondary, and supragastric belch-associated rumination. KEY RESULTS: Twenty-five consecutive patients (11 males, median age 13.3 years [IQR 5.9-15.8]) were included; recordings of 18 patients were suitable for analysis. Rumination events were identified in 16/18 patients, with 50% of events occurring <30 minutes postprandially. Fifteen of 16 patients showed ≥1 gastric pressure peak >30 mmHg, while only 50% of all events was characterized by peaks >30 mmHg and an additional 20% by peaks >25 mmHg. Four patients had evidence of acid GERD, all showing secondary rumination. CONCLUSIONS AND INFERENCES: Combined 24-hour pH-MII and manometry can be used to diagnose rumination syndrome in children and to distinguish it from GERD. Rumination patterns in children are similar compared with adults, albeit with lower gastric pressure increase. We propose a diagnostic cutoff for gastric pressure increase >25 mmHg associated with retrograde bolus flow into the proximal esophagus.

Computed critiquing integrated into daily clinical practice affects physicians' behavior--a randomized clinical trial with AsthmaCritic.

OBJECTIVE: We developed AsthmaCritic, a non-inquisitive critiquing system integrated with the general practitioners' electronic medical records. The system is based on the guidelines for asthma and chronic obstructive pulmonary disease (COPD) as issued by the Dutch College of General Practitioners. This paper assesses the effect of AsthmaCritic on monitoring and treatment of asthma and COPD by Dutch general practitioners in daily practice. METHODS: A randomized clinical trial in 32 practices (40 Dutch general practitioners) using electronic patient records. An intervention group was given the use of AsthmaCritic, a control group continued working in the usual manner. Both groups had the disposal of the asthma and COPD guidelines routinely distributed by the Dutch College of General Practitioners. We measured the average number of contacts, FEV 1 (forced expiratory volume), and peak-flow measurements per asthma/COPD patient per practice; and, the average number of antihistamine, cromoglycate, deptropine, and oral bronchodilator prescriptions per asthma/COPD patient per practice. RESULTS: The number of contacts increased in the age group of 12-39 years. The number of FEV1 , peak-flow measurements, and the ratio of coded measurements increased, whereas the number of cromoglycate prescriptions decreased in the age group of 12-39 years. CONCLUSIONS: Our study shows that the guideline-based critiquing system AsthmaCritic changed the manner in which the physicians monitored their patients and, to a lesser extent, their treatment behavior. In addition, the physicians changed their data-recording habits.

Reflux monitoring in children.

Recently, multichannel intraluminal impedance (MII) monitoring was added to the repertoire of tests to evaluate the (patho)physiology of gastroesophageal reflux (GER) in children. Its advantage above the sole monitoring of the esophageal pH lies in the ability of the detection of both acid and nonacid GER and to discern between liquid and gas GER. Currently, combined 24 h pH-MII monitoring is recommended for evaluation of gastro-esophageal reflux disease (GERD) and its relation to symptoms in infants and children, despite the lack of reference values in these age groups. There is new evidence in the current issue of this Journal supporting the role of pH-MII monitoring for the evaluation of children presenting with gastrointestinal symptoms suggestive of GERD and the prediction of the presence of reflux esophagitis. However, several issues should be taken into account when performing pH-MII clinically.

Macroscopic self-reorientation of interacting two-dimensional crystals.

Microelectromechanical systems, which can be moved or rotated with nanometre precision, already find applications in such fields as radio-frequency electronics, micro-attenuators, sensors and many others. Especially interesting are those which allow fine control over the motion on the atomic scale because of self-alignment mechanisms and forces acting on the atomic level. Such machines can produce well-controlled movements as a reaction to small changes of the external parameters. Here we demonstrate that, for the system of graphene on hexagonal boron nitride, the interplay between the van der Waals and elastic energies results in graphene mechanically self-rotating towards the hexagonal boron nitride crystallographic directions. Such rotation is macroscopic (for graphene flakes of tens of micrometres the tangential movement can be on hundreds of nanometres) and can be used for reproducible manufacturing of aligned van der Waals heterostructures.

Improved prediction of fatal myocardial infarction using the ankle brachial index in addition to conventional risk factors: the Edinburgh Artery Study.

BACKGROUND: Prediction of major cardiovascular and cerebrovascular events using conventional risk factor models is limited. Noninvasive measures of subclinical atherosclerosis such as the ankle brachial index (ABI) could improve risk prediction and provide more focused primary prevention strategies. We wished to determine the added value of a low ABI in the prediction of long-term risk of cardiovascular and cerebrovascular events and death. METHODS AND RESULTS: In 1988, 1592 men and women 55 to 74 years of age were randomly selected from the age-sex registers of 11 general practices in Edinburgh, Scotland, and followed up over a period of 12 years for incident events. After adjustment for age and sex, an ABI < or =0.9 was predictive of an increased risk of fatal myocardial infarction (MI), cardiovascular death, all-cause death, combined fatal and nonfatal MI, and total cardiovascular events. After further adjustment for prevalent cardiovascular disease, diabetes, and conventional risk factors, a low ABI was independently predictive of the risk of fatal MI. Addition of the ABI significantly (P< or =0.01) increased the predictive value of the model for fatal MI compared with a model containing risk factors alone. Comparison of areas under receiver operator characteristic curves confirmed that a model including the ABI discriminated marginally better than one without. CONCLUSIONS: Addition of the ABI significantly improved prediction of fatal MI over and above that of conventional risk factors. We recommend that the ABI be incorporated into routine cardiovascular screening and that the potential of its inclusion into cardiovascular scoring systems (with a view to improving their accuracy) now be examined.

An expert panel-based study on recognition of gastro-esophageal reflux in difficult esophageal pH-impedance tracings.

BACKGROUND: Despite existing criteria for scoring gastro-esophageal reflux (GER) in esophageal multichannel pH-impedance measurement (pH-I) tracings, inter- and intra-rater variability is large and agreement with automated analysis is poor. To identify parameters of difficult to analyze pH-I patterns and combine these into a statistical model that can identify GER episodes with an international consensus as gold standard. METHODS: Twenty-one experts from 10 countries were asked to mark GER presence for adult and pediatric pH-I patterns in an online pre-assessment. During a consensus meeting, experts voted on patterns not reaching majority consensus (>70% agreement). Agreement was calculated between raters, between consensus and individual raters, and between consensus and software generated automated analysis. With eight selected parameters, multiple logistic regression analysis was performed to describe an algorithm sensitive and specific for detection of GER. KEY RESULTS: Majority consensus was reached for 35/79 episodes in the online pre-assessment (interrater κ = 0.332). Mean agreement between pre-assessment scores and final consensus was moderate (κ = 0.466). Combining eight pH-I parameters did not result in a statistically significant model able to identify presence of GER. Recognizing a pattern as retrograde is the best indicator of GER, with 100% sensitivity and 81% specificity with expert consensus as gold standard. CONCLUSIONS & INFERENCES: Agreement between experts scoring difficult impedance patterns for presence or absence of GER is poor. Combining several characteristics into a statistical model did not improve diagnostic accuracy. Only the parameter 'retrograde propagation pattern' is an indicator of GER in difficult pH-I patterns.

Inter- and intrarater reliability of the Chicago Classification in pediatric high-resolution esophageal manometry recordings.

BACKGROUND: The Chicago Classification (CC) facilitates interpretation of high-resolution manometry (HRM) recordings. Application of this adult based algorithm to the pediatric population is unknown. We therefore assessed intra and interrater reliability of software-based CC diagnosis in a pediatric cohort. METHODS: Thirty pediatric solid state HRM recordings (13M; mean age 12.1 ± 5.1 years) assessing 10 liquid swallows per patient were analyzed twice by 11 raters (six experts, five non-experts). Software-placed anatomical landmarks required manual adjustment or removal. Integrated relaxation pressure (IRP4s), distal contractile integral (DCI), contractile front velocity (CFV), distal latency (DL) and break size (BS), and an overall CC diagnosis were software-generated. In addition, raters provided their subjective CC diagnosis. Reliability was calculated with Cohen's and Fleiss' kappa (κ) and intraclass correlation coefficient (ICC). KEY RESULTS: Intra- and interrater reliability of software-generated CC diagnosis after manual adjustment of landmarks was substantial (mean κ = 0.69 and 0.77 respectively) and moderate-substantial for subjective CC diagnosis (mean κ = 0.70 and 0.58 respectively). Reliability of both software-generated and subjective diagnosis of normal motility was high (κ = 0.81 and κ = 0.79). Intra- and interrater reliability were excellent for IRP4s, DCI, and BS. Experts had higher interrater reliability than non-experts for DL (ICC = 0.65 vs ICC = 0.36 respectively) and the software-generated diagnosis diffuse esophageal spasm (DES, κ = 0.64 vs κ = 0.30). Among experts, the reliability for the subjective diagnosis of achalasia and esophageal gastric junction outflow obstruction was moderate-substantial (κ = 0.45-0.82). CONCLUSIONS & INFERENCES: Inter- and intrarater reliability of software-based CC diagnosis of pediatric HRM recordings was high overall. However, experience was a factor influencing the diagnosis of some motility disorders, particularly DES and achalasia.

A quantitative study in the rat on the relationship between imipramine levels in brain and serum.

Serum and brain levels of the tricyclic antidepressant drug imipramine (IMI) were studied in the rat under a variety of conditions. IV doses (range 1 nmol kg-1 to 15 mumol kg-1, 350 ng--5 mg kg-1) and administered 5 min before death, were linearly correlated with IMI levels in serum, frontal cortex, and cerebellum. In this experiment, the highest levels of IMI were achieved in the frontal and occipital cortex and the lowest levels were found in the brain stem. The regional distribution was more even in rats pretreated with thiopental or gamma-hydroxybutyric acid, drugs that alter cerebral blood flow. After 20 min or more, tracer amounts of IMI injected IV to IMI-pretreated rats [1 or 17 days, daily dose 2 x 36 mumol kg-1 (10 mg kg-1), last dose 89 mumol kg-1 (25 mg kg-1), 2--3 h before death] exhibited a distribution pattern in serum and various brain regions similar to that of the unlabeled drug. In the latter experiments, content (per volume) of the tracer or unlabeled IMI was more than 25-fold higher in various brain areas than in serum. It is concluded that despite large differences in drug levels in serum or brain, a close relationship is maintained under the conditions studied.