The effect of visceral reception activation (water load test) on autonomic activity and gastric myoelectric activity in gastrointestinal malignancies.

OBJECTIVES: The aim of this study was to analyze the effect of water load test (WLT) on heart rate variability (HRV), blood pressure variability (BPV), hemodynamic parameters and gastric myoelectric activity in gastrointestinal (GI) cancer patients. BACKGROUND: WLT activates gastrointestinal mechanoreception and osmoreception, and hence, can indirectly modulate autonomic activity. METHODS: Eighty patients (mean age 61.2 years) were enrolled, along with the group of healthy controls. HRV, BPV and electrogastrography (EGG) were recorded at rest (in a fasted state) and after water uptake at 100 ml/min. RESULTS: WLT contributed to an increase in the percentages of normogastria time, from 37.3 % to 50.0 % (p=0.02) and from 42.3 % to 47.7 % (p=0.01), respectively in colon and rectal cancer. Cancer patients presented lower values of HRV indices determined on linear analysis at rest and after WLT. CONCLUSIONS: A slight predominance of the sympathetic component was observed in response to WLT, which was reflected by changes in hemodynamic parameters. The response to WLT is a consequence of GI mechanoreception and osmoreception activation and resultant pressure reaction. This effect was disrupted by the neoplastic process within the GI tract, especially in gastric and colon malignancies, but not in rectal cancer (Tab. 2, Fig. 12, Ref. 40). Text in PDF www.elis.sk Keywords: autonomic nervous system, gastric myoelectric activity, water uptake, heart rate variability, blood pressure variability, gastrointestinal cancer.

Interstitial cells of Cajal - systematic review.

This paper reviews the distribution of interstitial cells of Cajal (ICC) in the human gastro-intestinal (GI) tract, based on ultrastructural and immunohistochemical evidence. The distribution and morphology of ICC at each level of the normal GI tracts is addressed from the perspective of their functional significance. Alterations of ICC reported in as well as in GI stromal tumours are reviewed, with emphasis on the place of ICC in the pathophysiology of disease.

Self-efficacy, quality of life, and weight loss in overweight/obese endometrial cancer survivors (SUCCEED): a randomized controlled trial.

OBJECTIVE: More patient-centered programming is essential for endometrial cancer (EC) survivors needing to lose weight to reduce cardiovascular disease risk (CVD). The purpose of this study was to improve self-efficacy (SE) and quality of life (QOL) using a lifestyle intervention program designed for weight loss. METHODS: Overweight and obese early-stage EC survivors, n = 75, were randomized into two groups: 1) Survivors of Uterine Cancer Empowered by Exercise and Healthy Diet (SUCCEED), a six-month lifestyle intervention or 2) a usual care group (UC). Participants completed the Weight Efficacy Lifestyle Questionnaire (WEL) to assess SE and the Functional Assessment of Cancer Therapy-General (FACT-G) to measure QOL, and their body mass index (BMI) was calculated at baseline, 3, 6, and 12 months. Mixed, repeated-measures ANCOVA models with baseline covariates were employed using SPSS 20.0. RESULTS: Positive effects in every WEL domain, including the total score, were statistically significant in the SUCCEED group versus the UC group. A linear regression model demonstrated that, if BMI decreased by 1 unit, the total WEL score increased by 4.49 points. Significant negative correlations were found in the total WEL score and a change in BMI of R = -0.356 (p = 0.006). Between-group differences in the FACT-G were significant from baseline in the fatigue domain at three months (p = .008) and in the physical domain at six months (p = .048). No other significant differences were found. CONCLUSION: Overall, this study shows promise for targeted interventions to help improve SE, thus improving BMI.

Morphology and Mechanics of the Fin Whale Esophagus: The Key to Fast Processing of Large Food Volumes by Rorquals.

Lunge feeding rorqual whales feed by engulfing a volume of prey laden water that can be as large as their own body. Multiple feeding lunges occur during a single foraging dive and the time between each lunge can be as short as 30 s (Goldbogen et al. 2013). During this short inter-lunge time, water is filtered out through baleen to concentrate prey in the oral cavity, and then the prey is swallowed prior to initiating the next lunge. Prey density in the ocean varies greatly, and despite the potential of swallowing a massive volume of concentrated prey as a slurry, the esophagus of rorqual whales has been anecdotally described as unexpectedly narrow with a limited capacity to expand. How rorquals swallow large quantities of food down a narrow esophagus during a limited inter-lunge time remains unknown. Here, we show that the small diameter muscular esophagus in the fin whale is optimized to transport a slurry of food to the stomach. A thick wall of striated muscle occurs at the pharyngeal end of the esophagus which, together with the muscular wall of the pharynx, may generate a pressure head for transporting the food down the esophagus to the stomach as a continuous stream rather than separating the food into individual boluses swallowed separately. This simple model is consistent with estimates of prey density and stomach capacity. Rorquals may be the only animals that capture a volume of food too large to swallow as a single intact bolus without oral processing, so the adaptations of the esophagus are imperative for transporting these large volumes of concentrated food to the stomach during a time-limited dive involving multiple lunges.

The Soft Palate Enables Extreme Feeding and Explosive Breathing in the Fin Whale (Balaenoptera physalus).

The evolution of lunge feeding in rorqual whales was associated with the evolution of several unique morphological features that include non-synovial ligamentous temporomandibular joints, a tongue that can invert and extend backward to the umbilicus, walls of the oral cavity that can dramatically expand, and muscles and nerves that are stretchy. Also, among the acquired features was an enlargement of the rostral end of the soft palate into an oral plug that occludes the opening between the oral cavity and pharynx and prevents water incursion into the pharynx during the engulfment phase of a feeding lunge. During this engulfment phase of a lunge, the volume of water entering the oral cavity can exceed the volume of the whale itself. Here, using dissection of fetuses and adults and a magnetic resonance imaging dataset of a fetus, we examine the detailed anatomy of the soft palate in fin whales. We describe several innovative features relative to other mammals, including changes in the attachment and positions of the major extrinsic muscles of the palate, alterations in the morphology of the pterygoid processes related to the palate and pharynx, and the presence of distinct muscle layers in the part of the palate caudal to the oral plug. Based on the anatomy, we present a model for how the soft palate is positioned at rest, and how it functions during feeding, breathing, and swallowing.

Effects of water ingestion on autonomic activity and gastric motility in patients with celiac disease.

The pathogenesis of celiac disease is associated with an autoimmune process. The disease causes chronic inflammation of the small intestinal mucosa, which may affect the brain-gut axis. The activation of visceral receptors (gastrointestinal mechanoreceptor and osmoreceptor) in response to stomach distension caused by water ingestion has not been studied before. Our results showed reduced responsiveness of the autonomic nervous system to water ingestion in patients with celiac disease, which may lead to disturbances of gastric myoelectrical activity and depends on baseline autonomic activity. Water intake can induce gastric distension and motility response, without changes in gastrointestinal hormones. It can also increase the activity of the autonomic nervous system. On the other hand, inflammation in celiac disease (CeD) can alter visceral perception (increase sensitization), leading to autonomic dysfunction. We aimed to investigate the effect of water ingestion on autonomic activity measured as heart rate variability (HRV) and gastric myoelectrical activity measured by electrogastrography (EGG) in patients with CeD. The study included 53 patients with CeD and 50 healthy controls: mean (SD) age, 43.4 (14.8) years and 44.1 (9.2) years, respectively. Electrocardiography with HRV analysis and simultaneous 4-channel EGG was performed before and after the water load test (WLT) ingestion 500-ml water over 5 minutes. We found that compared with controls, at fasting, patients with CeD showed a reduced percentage of normogastria (P=0.045) and an average percentage of slow wave coupling (P<0.01) with increased dominant power (DP) (P<0.001). Moreover, water ingestion in CeD patients reduced the percentage of gastric arrhythmia (P<0.01) and increased the percentage of normogastria (P<0.01) and DP (P<0.01). Finally, in the CeD group, water ingestion increased HRV indices: low frequency by 116.9% (P<0.001), high frequency by 125.3% (P<0.01), but they did not reach the values of the control group. Patients with CeD showed a smaller increase in parasympathetic autonomic activity after the WLT than controls. Altered autonomic responsiveness may contribute to the disturbances of gastric myoelectrical activity and depends on baseline autonomic activity.

Phagocytosis of latex beads by a human monocytic Mono Mac 6 cell line and effects of low-frequency electromagnetic field interaction.

Some studies have shown that electromagnetic fields (EMFs) may impact immune response cells and their functions. The first stage of the defense from pathogens is innate immunity encompassing phagocytosis and phagocytosis-related intracellular effects. Our work aimed to determine the influence of a low-frequency electromagnetic field (7 Hz, 30 mTrms) on the phagocytosis process of latex beads (LBs), the production of reactive oxygen species (ROS), and viability changes in a human monocytic Mono Mac 6 (MM6) cell line as an experimental model of the phagocytosing cells in in vitro cell culture conditions. For these purposes, cells were firstly activated with infectious agents such as lipopolysaccharide (LPS), Staphylococcal enterotoxin B (SEB), or the proliferatory agent phytohaemagglutinin (PHA), and then a phagocytosis test was performed. Cell viability and range of phagocytosis of latex beads by MM6 cells were measured by flow cytometry, and the level of ROS was evaluated with the use of a cytochrome C reduction test. The obtained results revealed that applied EMF exposure mainly increased the necrosis parameter of cell death when they were pre-stimulated with SEB as an infectious factor and subsequently phagocytosed LBs (P=0.001). Prestimulation with other agents like LPS or PHA preceding phagocytosis resulted in no statistically significant changes in cell death parameters. The level of ROS depended on the used stimulatory agent, phagocytosis, and/or EMF exposure. The obtained effects for EMF exposure indicated only a slight decrease in the ROS level for cells phagocytosing latex beads and being treated with SEB or PHA, while the opposite effect was observed for LPS pre-stimulated cells (data not statistically significant). The results concerning the viability of phagocytosing cells, the effectiveness of the phagocytosis process, and the level of radical forms might result from applied EMF parameters like signal waveform, frequency, flux density, and especially single EMF exposure.

Type of desmin expression in cardiomyocytes - a good marker of heart failure development in idiopathic dilated cardiomyopathy.

AIM: The aim of this study was to determine whether remodelling of the desmin (DES) cytoskeleton affects myocardial function and whether it could be a useful marker of disease progression in patients with idiopathic dilated cardiomyopathy (IDCM). MATERIAL AND METHODS: Endomyocardial biopsy was performed in 195 IDCM patients, and five to six specimens were collected from the left ventricle. DES expression was evaluated using tissue immunostaining and Western blotting. The study population was assigned to four groups according to DES expression type: I, normal DES staining at Z-lines giving a regular pattern of cross-striation (n = 57); IIA, increased DES staining with a regular pattern of cross-striation (n = 40); IIB, increased DES staining with an irregular pattern of cross-striation and/or the presence of aggregates (n = 56); and III, decreased/lack of DES staining (n = 42). Fibrosis, cardiomyocyte hypertrophy and ultrastructure were assessed for the four types of DES expression. RESULTS: The pathological types of DES expression (IIB or III) were associated with pathological changes in mitochondria and the contractile apparatus. Cardiomyocyte diameter and level of fibrosis were both significantly affected. DES expression type correlated with NYHA class, left ventricular end-diastolic diameter, left ventricular ejection fraction and the level of N-terminal pro-brain natriuretic protein. CONCLUSION: The type of immunohistochemical DES expression correlated with the level of myocardial injury at the cellular and organ levels. This correlation was similar to that observed between DES expression and the well-established biochemical, echocardiographic and clinical parameters of heart failure (HF). DES expression type could be used as an important diagnostic feature of HF development.

Abscisic acid-mediated phytochrome B signaling promotes primary root growth in Arabidopsis.

Plant photomorphogenic responses have been studied mostly using the shoots, the core part of plant architecture that perceives light for photosynthesis and influences the overall processes of growth and development. While the roots are also known to respond to aboveground light through multiple routes of light signal transduction, root photomorphogenesis has been less highlighted until recently. A long-standing, critical question was how the underground roots are capable of sensing aerial light and how the root-sensed light signals trigger root photomorphogenesis. When the roots are directly exposed to light, reactive oxygen species (ROS) are rapidly produced to promote primary root elongation, which helps the roots to escape from the abnormal growth conditions. However, severe or long-term exposure of the roots to light causes ROS burst, which impose oxidative damages, leading to a reduction of root growth. We have recently found that phytochrome B (phyB) promotes abscisic acid (ABA) biosynthesis in the shoots and the shoot-derived ABA signals mediate ROS detoxification in the roots, lessening the detrimental effects of light on root growth. On the basis of these observations we propose that the phyB-mediated ABA signaling contributes to the shoot-root synchronization that is essential for optimal growth and performance in plants.

Urinary neutrophil gelatinase-associated lipocalin, kidney injury molecule-1, uromodulin, and cystatin C concentrations in an experimental rat model of ascending acute kidney injury induced by pyelonephritis.

Recent evidence suggests that neutrophil gelatinase-associated lipocalin (NGAL), kidney injury molecule-1 (KIM-1), cystatin C (CysC), uromodulin (UMOD), and some interleukins (IL-6 and IL-18) can be considered as diagnostic markers of acute kidney injury (AKI). The aim of this study was to verify the applicability of four urinary (u) markers, namely uNGAL, uKIM-1, uCysC, and uUMOD, for the diagnosis of ascending AKI induced by bacterial pyelonephritis. The study included 30 female rats that were divided into three groups (n = 10 each) and were inoculated transurethrally with various doses of Escherichia coli to induce isolated pyelonephritis (group 1, 105 CFU/ml), pyelonephritis-induced AKI (group 2, 107 CFU/ml), or AKI and urosepsis (group 3, 109 CFU/ml). The inoculate contained a highly virulent E. coli strain isolated from a patient with pyelonephritis. Urine samples were obtained prior to the inoculation and 7, 14, and 21 days thereafter. The concentrations of all assessed proteins were determined in the urine samples by ELISA. All the study groups showed elevated concentrations of uNGAL and uCysC at all study time points. The concentrations of uKIM-1 in group 1 were the same as that at the baseline, whereas it was elevated in groups 2 and 3 at all study time points. The concentrations of uUMOD in groups 1 and 2 tended to decrease with the time from inoculation, whereas it rapidly increased in group 3 at 21 days postinfection. uKIM-1 seems to be the only marker of ascending AKI associated with urinary tract infection. Elevated concentrations of uNGAL, uCysC, and uUMOD were found in both AKI and isolated pyelonephritis. Thus, it can be concluded that none of these markers can be used as a single diagnostic marker of ascending AKI, as it may produce false-negative results, leading to incorrect diagnosis, lack of adequate treatment, and increased mortality risk.

Melatonin and serotonin effects on gastrointestinal motility.

The gastrointestinal tract represents the most important extra pineal source of melatonin. Presence of melatonin (M) suggests that this hormone is somehow involved in digestive pathophysiology. Release of GI melatonin from serotonin-rich enterochromaffin EC cells of the GI mucosa suggest close antagonistic relationship with serotonin (S) and seem to be related to periodicity of food intake. Food deprivation resulted in an increase of tissue and plasma concentrations of M. Its also act as an autocrine and paracrine hormone affecting not only epithelium and immune system but also smooth muscle of the digestive tract. Low doses M improve gastrointestinal transit and affect MMC. M reinforce MMCs cyclic pattern but inhibits spiking bowel activity. Pharmacological doses of M delay gastric emptying via mechanisms that involve CCK2 and 5HT3 receptors. M released in response to lipid infusion exerts a modulatory influence that decreases the inhibitory effects of the ileal brake on gastric emptying. On isolated bowel S induces dose dependent increase in tone and reduction in amplitude of contraction which is affected by M. M reduced the tone but not amplitude or frequency of contraction. M is a promising therapeutic agent for IBS with activities independent of its effects on sleep, anxiety or depression. Since of its unique properties M could be considered for prevention or treatment of colorectal cancer, ulcerative colitis, gastric ulcers and irritable bowel syndrome.

Vacuum and forceps training in residency: experience and self-reported competency.

OBJECTIVE: Determine chief residents' experience with vacuum and forceps deliveries and self-perceived competencies with the procedures. STUDY DESIGN: Study 1: A written questionnaire was mailed to all fourth year residents in US RRC approved Ob/Gyn programs. Study 2: The study was replicated using a web-based survey the following year. Data were analyzed with chi (2) and Wilcoxon Signed Rank tests using SPSS. RESULTS: Surveys were received from 238 residents (20%) in Study 1 and 269 residents in Study 2 (23%, representing 50% of all residency programs). In both studies, residents reported performing significantly less forceps than vacuum deliveries. Virtually all residents wanted to learn to perform both deliveries, indicated attendings were willing to teach both, and felt competent to perform vacuum deliveries (Study 1, 94.5%; Study 2, 98.5%); only half felt competent to perform forceps deliveries (Study 1, 57.6%; Study 2, 55.0%). The majority of residents who felt competent to perform forceps deliveries reported that they would predominately use forceps or both methods of deliveries in their practice (Study 1, 75.8%; Study 2, 64.6%). The majority of residents who reported that they did not feel competent to perform forceps deliveries reported that they would predominately use vacuum deliveries in their practice (Study 1, 86.1%; Study 2, 84.2%). CONCLUSION: Current training results in a substantial portion of residents graduating who do not feel competent to perform forceps deliveries. Perceived competency affected future operative delivery plans.

Changes in viability of rat adipose-derived stem cells isolated from abdominal/perinuclear adipose tissue stimulated with pulsed electromagnetic field.

Previous experiments demonstrated that low-frequency electromagnetic field (LF-EMF) may activate cellular death pathways in proliferating cells. Therefore, we hypothesized that LF-EMF may also influence viability of highly proliferating undifferentiated adipose-derived stem cells. Obesity is classified as a civilization disease; its etiopathogenesis is presumed to include both genetic predisposition and influence of modified environmental factors, such as unbalanced diet with excess calories and/or too low physical activity. Obesity may lead to a number of metabolic disorders, including type 2 diabetes mellitus, cardiovascular diseases (associated with atherosclerosis) related to primary hypertension and ischemic heart disease, myocardial infarction and other complications. The aim of this study was to verify if LF-EMF alters viability parameters of adipose-derived stem cells (ADSCs) isolated from rats, cultured in vitro and exposed to pulsed electromagnetic field (PEMF; 7 Hz, 30 mT). ADSCs were obtained from healthy rats and animals with experimentally-induced obesity, both males and females, pups and adults. The animals were fed with chow with either low (LF diet) or high fat content (HF diet) for 21 days. Then, ADSCs were isolated from extracted adipose tissue and used to establish cell cultures. ADSCs from the first passage were exposed to PEMF three times, 4 hours per exposure, at 24-h intervals (experimentally developed protocol of PEMF stimulation). 24 hours after the last exposure to PEMF, viability parameters of ADSCs were analyzed by flow cytometry (FCM). The study demonstrated that LF diet exerted a protective effect on PEMF-exposed ADSCs, especially in the case of male and female pups. In turn, the proportion of early apoptotic cells in PEMF-treated ADSC cultures from adult female rats maintained on HF diet turned out to be significantly higher than in other experimental groups.

Peripheral mechanisms of intestinal dysmotility in rats with salsolinol induced experimental Parkinson's disease.

Gastrointestinal dysmotility in Parkinson's disease (PD) has been attributed in part to peripheral neurotoxine action. Our purpose was the evaluation of the salsolinol effect on intramuscular interstitial cells of Cajal (ICC), duodenal myoelectrical activity (DMA) and vagal afferent activity (VAA) in rats with experimental PD. Twenty rats were divided into 2 equal groups. Experimental PD was produced in one group by 3 weeks of the intraperitoneal salsolinol injections (50 mg/kg/day), whereas the 2-nd group served as control. DMA and VAA were recorded in both groups during fasting and stepwise--gastric distension (GD) of 10 ml. Subsequently fragments of duodenum were removed and intramuscular ICC were assessed as c-Kit antigen percentage in the duodenal muscular zone. Analyses of the fasting DMA and VAA recordings didn't reveal differences between the compared groups. During GD increase of DMA dominant frequency (p=0.04) and VAA frequency (p<0.01) was observed in the controls whereas in the salsolinol group both parameters remained unchanged. Image analysis of duodenum revealed decreased c-Kit expression in the salsolinol-injected animals (p=0.05). The results of our study may suggest the direct effect of salsolinol on both ICC and neuronal pathways of gastro-duodenal reflexes.

Peripheral mechanisms of intestinal dysmotility in the morphine tolerant and dependent rats.

Changes of intestinal motility and transit produced by tolerance to and dependence upon morphine have been partly attributed to peripheral mechanisms. We evaluated the effect of chronic peripheral morphine administration and peripheral mu-receptor blockade on vagal afferent activity (VAA) and c-Kit positive intramuscular cells of Cajal (ICCs). Ten rats were subjected to chronic subcutaneous morphine infusion for 72 h with subsequent VAA recording. Potential frequency was evaluated within recordings before and after mu receptor blockade by (D)-Phe -Cys -Tyr -(D)-Trp -Orn -Thr -Phe -Thr (CTOP) i.p. injections. Afterwards the rats were sacrificed and intramuscular c-Kit antigen expression was assessed by image analysis within removed fragments of duodenum and ascending colon. An equal group of rats served as a control for VAA and c-Kit expression. Analysis of VAA revealed similar frequencies of potentials in morphine tolerant / dependent rats before CTOP and in the controls. CTOP increased potential frequency in the morphine group which effect was visible mostly within the first 20 minutes (p=0.01). The morphine infused animals presented also higher c-Kit expression in both the duodenum (p<0.001) and the ascending colon (p<0.001) in comparison to the control group. Results of our study may indicate the involvement of both the intestinal wall and the long vago-vagal reflexes in tolerance to and dependence upon opioids.

Characteristics of litter waste in highway storm runoff.

Litter characterization is an integrated part of the Caltrans First Flush Characterization Study. These data will provide a basis to develop potential treatment technologies and best management practices to control pollutants in runoff from freeways. During monitoring periods in Southern California areas, the first flush phenomenon was evaluated and the impacts of various parameters such as rain intensity, drainage area, peak flow rate, and antecedent dry period on litter volume and loading rates were evaluated. First flush phenomenon was generally observed for litter concentrations, but was not apparent with litter mass loading rates. Total captured gross pollutants, defined as larger than 0.5 cm, was 90% vegetation with only 10% being litter. The normalized cumulative litter loadings were determined from 1.25 to 13.39 kg/ha for dry litter weight and 0.40 to 8.99 kg/ha for dry biodegradable litter weight. The portions of biodegradable litter to non-biodegradable litter were roughly the same across the entire event. Event mean concentrations were ranged 0.0021 to 0.259 g/L for wet gross pollutants, 0.0001 to 0.027 g/L for wet litters and 0.00007 to 0.018 g/L for dry litters. The mass emission rates should be useful to estimate total litter production for developing total maximum daily loads.

Loss of interstitial cells of Cajal after pulsating electromagnetic field (PEMF) in gastrointestinal tract of the rats.

Exposure to the magnetic field has remarkably increased lately due to fast urbanization and widely available magnetic field in diagnosis and treatment. However, biological effects of the magnetic field are not well recognized. The myoelectric activity recorded from the gastrointestinal and urinary systems is generated by specialized electrically active cells called interstitial cells of Cajal (ICCs). Thus it seems rational that ICC have significant vulnerability to physical factors like an electromagnetic field. The aim of this study was to evaluate the influence of pulsating electromagnetic field (PEMF) (frequency 10 kHz, 30ms, 300 muT burst, with frequency 1Hz) on ICCs density in the rat gastrointestinal tract. Rats were divided into two groups (n=32). The first group was exposed to PEMF continuously for 1, 2, 3, and 4 weeks (n = 16), and the second group (n=16) served as a control. Tissue samples of the rat stomach, duodenum and proximal colon were fixed and paraffin embedded. The tangential sections of 5 microm thickness were stained immunohistochemically with anti-c-Kit (sc-168) antibody and visualized finally by DAB as chromogen (brown end product). C-Kit positive branched ICC-like cells were detected under the light microscope, distinguished from the c-kit-negative non-branched smooth muscle cells and from the c-kit positive but non-branched mast cells and quantitatively analyzed by MultiScan computer program. Apoptosis detection was performed with rabbit anti-Bax polyclonal antibody (Calbiochem, Germany) and LSAB 2 visualization system. The surface of c-Kit immunopositive cells decreased after exposure to PEMF in each part of the gastrointestinal tract. Reduced density of ICCs was related to exposure time. The most sensitive to PEMF were ICCs in the fundus of the stomach and in the duodenum, less sensitive were ICCs in the colon and pacemaker areas of the stomach. No marked changes in ICC density in the pyloric part of the stomach were observed. We demonstrate that the PEMF induced apoptosis dependent decrease in ICC expression.

Gastric emptying in humans: influence of different regimens of parenteral nutrition.

Intravenous administration of nutrients can suppress oral food intake. Inhibition of gastric emptying (GE) is a potential explanation for this process. Inhibition of GE during parenteral nutrition (PN) and attenuation of this by parenteral nutrition enriched with branched-chain amino acids (BCAAs) was examined in nine healthy males maintained on standard liquid diets for 6 d before each of three GE studies. GE was measured by scintigraphy after ingestion of a liquid test meal, at weekly intervals, after a 6-h infusion of Ringer lactate solution (RL), peripheral PN, or PN with half the amino acids replaced with BCAAs (BCPN). With PN, gastric emptying during the first 50 min was delayed by 38% compared with RL infusion; BCPN attenuated the effect, suggesting that postabsorptive control of food intake may act through changes in GE. These findings have clinical potential to reduce interference with appetite and to optimize food intake during PN administration.

A multicenter study of the efficacy of the ketogenic diet.

OBJECTIVE: To determine the efficacy of the ketogenic diet in multiple centers. DESIGN: A prospective study of the change in frequency of seizures in 51 children with intractable seizures who were treated with the ketogenic diet. SETTING: Patients were enrolled from the clinical practices of 7 sites. The diet was initiated in-hospital and the patients were followed up for at least 6 months. PATIENTS: Fifty-one children, aged 1 to 8 years, with more than 10 seizures per week, whose electroencephalogram showed generalized epileptiform abnormalities or multifocal spikes, and who had failed results when taking at least 2 appropriate anti-epileptic drugs. INTERVENTION: The children were hospitalized, fasted, and a 4:1 ketogenic diet was initiated and maintained. MAIN OUTCOME MEASURES: Frequency of seizures was documented from parental calendars and efficacy was compared with prediet baseline after 3, 6, and 12 months. The children were categorized as free of seizures, greater than 90% reduction, 50% to 90% reduction, or lower than 50% reduction in frequency of seizures. RESULTS: Eighty-eight percent of all children initiating the diet remained on it at 3 months, 69% remained on it at 6 months, and 47% remained on it at 1 year. Three months after initiating the diet, frequency of seizures was decreased to greater than 50% in 54%. At 6 months, 28 (55%) of the 51 initiating the diet had at least a 50% decrease from baseline, and at 1 year, 40% of those starting the diet had a greater than 50% decrease in seizures. Five patients (10%) were free of seizures at 1 year. Age, sex, principal seizure type, and electroencephalogram were not statistically related to outcome. CONCLUSION: The ketogenic diet is effective in substantially decreasing difficult-to-control seizures and can successfully be administered in a wide variety of settings.

No evidence for a major susceptibility locus for juvenile myoclonic epilepsy on chromosome 15q.

Juvenile myoclonic epilepsy (JME) is a distinct epileptic syndrome with a complex mode of inheritance. Several studies found evidence for a locus involved in JME on chromosome 6 near the HLA region. Recently, Elmslie et al. [1997] reported evidence of linkage in JME to chromosome 15q14 assuming a recessive mode of inheritance with 50% penetrance and 65% linked families. The area on chromosome 15q14 encompasses the location of the gene for the alpha-7 subunit of the nicotinic acetylcholine receptor. This could fit the hypothesis that there are two interacting loci, one on chromosome 6 and on chromosome 15 or that there is genetic heterogeneity in JME. In an independent dataset of JME families, we tested for linkage to chromosome 15 but found little evidence for linkage. Moreover, families with more than one family member affected with JME provide a lodscore of 3.4 for the HLA-DR/DQ haplotype on chromosome 6. The lodscore for these same families on chromosome 15q14 is <-2 assuming homogeneity and the maximum lodscore is 0.2 assuming alpha =.25. Only one of these families has a negative lodscore on chromosome 6 and a positive lodscore of 0.5 on chromosome 15q14. Our results indicate that this possible gene on chromosome 15 plays at most a minor role in our JME families. Am. J. Med. Genet. (Neuropsychiatr. Genet.) 96:49-52, 2000.