Variations in diet cause alterations in microbiota and metabolites that follow changes in disease severity in a multiple sclerosis model.

Multiple sclerosis (MS) is a metabolically demanding disease involving immune-mediated destruction of myelin in the central nervous system. We previously demonstrated a significant alteration in disease course in the experimental autoimmune encephalomyelitis (EAE) preclinical model of MS due to diet. Based on the established crosstalk between metabolism and gut microbiota, we took an unbiased sampling of microbiota, in the stool, and metabolites, in the serum and stool, from mice (Mus musculus) on the two different diets, the Teklad global soy protein-free extruded rodent diet (irradiated diet) and the Teklad sterilisable rodent diet (autoclaved diet). Within the microbiota, the genus Lactobacillus was found to be inversely correlated with EAE severity. Therapeutic treatment with Lactobacillus paracasei resulted in a significant reduction in the incidence of disease, clinical scores and the amount of weight loss in EAE mice. Within the metabolites, we identified shifts in glycolysis and the tricarboxylic acid cycle that may explain the differences in disease severity between the different diets in EAE. This work begins to elucidate the relationship between diet, microbiota and metabolism in the EAE preclinical model of MS and identifies targets for further study with the goal to more specifically probe the complex metabolic interaction at play in EAE that may have translational relevance to MS patients.

The Enigma of Rapid Repeat Pregnancy: A Qualitative Study of Teen Mothers.

STUDY OBJECTIVE: Rapid repeat pregnancy accounts for 18% of teen pregnancies and leads to adverse health, economic, and developmental outcomes for teen mothers and their children. Few interventions have been successful in reducing rapid repeat pregnancy. In this qualitative study we examined adolescent mothers' perceptions of their decision-making and behaviors that helped prevent or promote a rapid repeat pregnancy. DESIGN, SETTING, PARTICIPANTS, INTERVENTIONS, AND MAIN OUTCOME MEASURES: Semistructured interviews were conducted with 31 adolescent mothers, aged 16-21 years; 15 of these subjects experienced a repeat pregnancy within a year of their first child's birth and 16 had not. Two researchers used a grounded, inductive technique to identify emergent themes; interviews were subsequently coded accordingly. Counts were tabulated of the number of times themes were endorsed among those with or without a repeat pregnancy. RESULTS: Four overarching themes emerged from the interviews: intentionality regarding pregnancy planning, patients' degree of independence in making contraceptive choices, sense of control over life experience, and barriers to follow-through on contraceptive planning. Teens who had not experienced a rapid repeat pregnancy more often endorsed themes of intentionality in preventing or promoting a pregnancy, independence in decision-making, and feelings of control over their experience. Ambivalence and lack of decision-making about seeking another pregnancy were frequently endorsed by mothers who had experienced a second pregnancy. CONCLUSION: Decision-making regarding seeking or preventing a rapid repeat pregnancy is complex for teen mothers; techniques to help support decision-making or to delay pregnancy until decision-repeat making is complete might be important in reducing rapid pregnancy.

Efficacy of deferred dosing of granulocyte colony-stimulating factor in autologous hematopoietic transplantation for multiple myeloma.

Routine administration of G-CSF following autologous hematopoietic SCT (ASCT) expedites ANC recovery and reduces hospitalization by 1-2 days; it has no impact on febrile neutropenia, infections, morbidity, mortality, event-free survival or OS. To determine whether delayed G-CSF dosage could result in equivalent ANC recovery and thereby improve cost effectiveness, we deferred the administration of G-CSF until WBC recovery had begun. A total of 117 patients with multiple myeloma received ASCT from January 2005 to September 2012. Of these, 52 were in the conventional dosing group (CGD) and received G-CSF from Day +7 for a median of five doses. In the deferred dosing group (DGD), 65 patients received G-CSF from median day 14 post transplant for a median of zero doses. There was no difference between groups in the incidence or duration of febrile neutropenia, duration of grade III mucositis, weight gain, rash, engraftment syndrome or early death (100 days). The DGD group had a significantly longer time to neutrophil engraftment than the CGD group (15 days vs 12 days; P<0.0001), a longer period of severe neutropenia (<100/µL; 8 days vs 6 days; P<0.0001), longer treatment with intravenous antibiotics (7 days vs 5 days; P=0.016) and longer hospital stay (19 days vs 17 days; P=<0.0001). Although the cost of G-CSF was lower in the DGD group (mean $308 vs $2467), the additional hospitalization raised the median total cost of ASCT in this group by 17%. There was, however, no adverse effect of deferred dosing on the rate of febrile neuropenic episodes or Day 100 survival, so that deferred dosing of G-CSF may be suitable for patients receiving ASCT as outpatients, for whom longer hospital stay would not be an offsetting cost.

Jejunal or portal vein infusions of lipids increase hepatic vagal afferent activity.

Jejunal infusions of linoleic acid, corn oil, or caprylic acid significantly increased hepatic vagal afferent activity, whereas saline infusions were ineffective. The magnitude of response was greatest with either linoleic acid or corn oil. Hepatic portal infusions of linoleic acid, Liposyn II, or caprylic acid significantly increased hepatic vagal afferent activity, whereas 5% albumin/phosphate buffer vehicle was ineffective. The magnitude of response was greatest with either linoleic acid or Liposyn II. These data show that either jejunal or portal infusions of lipids increase activity of hepatic vagal afferents and could potentially serve as a complementary and/or alternative substrate to celiac vagal afferents in mediating the effects of jejunal infusions of lipids in suppressing food intake.

Celiac vagotomy reduces suppression of feeding by jejunal fatty acid infusions.

We investigated the role of the celiac branch of the vagus nerve in suppression of food intake produced by jejunal fatty acids infusions. Following selective celiac vagotomy or sham surgery, adult, male Sprague-Dawley rats received 7 h infusions of linoleic acid or saline through indwelling jejunal catheters on four consecutive days. Although linoleic acid still produced significant suppression of intake in rats with celiac vagotomy, it was less effective in these animals than in controls. The temporal pattern of results suggested that celiac afferent fibers are involved in mediating both pre- and postabsorptive effects of infused fatty acids.

Changes in plasma gonadotrophin and prolactin concentrations following castration of the pony stallion.

Concentrations of gonadotrophins and prolactin were recorded in pony stallions castrated during the early breeding season, to examine the regulatory role of the gonad at a time when testosterone has been postulated to exert positive feedback on LH secretion. Further, gonadotrophin concentrations in geldings are reported to return to values within the normal range of the entire stallion. In an attempt to characterize this species-specific reversal, the gonadotrophin concentrations of 6 male ponies castrated on 25 March were monitored for 4 months, and 4 stallions were used to generate control data. Blood samples were collected daily, from 3 d before to 10 d after castration (Day 0), and weekly thereafter until Day 122. The pituitary response to castration was immediate. Castration resulted in a previously unreported, dramatic (13-fold) but transient (3 d) surge in circulating concentrations of LH. Concentrations of LH and FSH increased in a logarithmically scaled (LH, R2 = 0.77; FSH, R2 = 0.93) manner over the subsequent 5 wk, during which temporal changes in concentrations of both hormones were strongly correlated (R2 = 0.97). The ratio of plasma gonadotrophin concentrations was consistent throughout (LH:FSH, 1.43 +/- 0.04). Maximal concentrations of LH (20.58 +/- 1.97 ng/mL, Day 34.8 +/- 3.2) were attained approximately 2 wk before the peak in FSH (16.99 +/- 1.97 ng/mL, Day 49.7 +/- 3.0). Plasma gonadotrophin concentrations exceeded those of entire stallions throughout the study. The equine testes inhibited LH secretion during the early breeding season, and no chronic decrease in plasma gonadotrophin concentrations was recorded. However, the LH surge evident for 3 d immediately afer castration, may be related to the dynamic seasonal interaction between gonadal steroids and the regulation of pituitary gonadotrophin release.

The utility of screening chest radiographs for flight physicals.

Previous studies have shown low efficacy of screening chest radiographs in various populations. Findings of approximately 3,500 screening chest radiographs performed for flight duty were reviewed to determine the rate of detection of significant abnormalities. There were abnormal findings in 107 chest radiographs (3%). Fifty-five of these (1.6% of total), after additional evaluation, were found to be false positive. Only two medically significant conditions were found in the screening population. Based on our data, routine screening of flight duty applicants does not appear to be justified.

Suppression of food intake, body weight, and body fat by jejunal fatty acid infusions.

Three experiments investigated effects of jejunal lipid infusions given on 4 or 21 consecutive days in adult, male Sprague-Dawley rats. In experiment 1, 7-h infusions of linoleic or oleic acid (0.2 ml/h for 7 h; total load = 11.5 kcal) on 4 consecutive days reduced total intake (ad libitum consumption of the liquid diet Boost, Mead Johnson, plus load) by approximately 15% and decreased weight gain compared with 4-day tests with saline administration. In experiment 2, linoleic acid at 0.1 ml/h for 7 h (5.7 kcal) was ineffective, whereas the same load delivered in 3.5 h produced effects similar in magnitude to those in the first experiment. In experiment 3, jejunal infusions of linoleic acid (0.2 ml/h for 7 h) on 21 consecutive days reduced mean total intake by 16%, body weight by 10%, and carcass fat by 48% compared with controls receiving saline. The net decrease in caloric intake may reflect the combined activation of pre- and postabsorptive mechanisms, and it suggests a possible treatment for obesity.

Responses of celiac and cervical vagal afferents to infusions of lipids in the jejunum or ileum of the rat.

Multiunit celiac and single-unit cervical recordings of vagal afferents were performed before and during infusions of fatty acids, triglycerides, or saline into either the ileum or jejunum of the rat. In multiunit recordings, lipids increased activity of vagal afferents to a greater extent than saline. The greatest increases in vagal afferent activity resulted from infusions of linoleic acid, conjugated linoleic acid, or oleic acid. The triglycerides, corn oil or Intralipid, were less effective than the fatty acids in affecting vagal afferent activity. Ileal pretreatment with the hydrophobic surfactant Pluronic L-81 significantly attenuated the response of celiac vagal afferents to ileal infusion of linoleic acid. Single-unit recordings of cervical vagal afferents supported the multiunit data in showing lipid-induced increased vagal afferent activity in approximately 50% of ileal units sampled and 100% of a limited number of jejunal units sampled. These data demonstrate that free fatty acids can activate ileal and jejunal vagal afferents in the rat, and this effect can be attenuated by pretreatment with a chylomicron inhibitor. These data are consistent with the view that lipid-induced activation of vagal afferents could be a potential substrate for the inhibitory effects of intestinal lipids on gastrointestinal function, food intake, and body weight gain.

The meaning of home: how it shapes the practice of home and hospice care.

Nurses often hear clients and their families express a strong desire to "go home" from the hospital or nursing home. The purpose of this article is to explore what they mean when they make this request and how this meaning of home can shape the practice of home and hospice care. To do this, definitions of home and a health-at-home model are described and applied through a case study.

Transthoracic needle aspiration biopsy: variables that affect risk of pneumothorax.

PURPOSE: To analyze the influence of multiple variables on the rate of pneumothorax and chest tube placement associated with transthoracic needle aspiration biopsy of the lung. MATERIALS AND METHODS: In 346 patients, 331 computed tomographically (CT) guided and 24 fluoroscopically guided lung biopsies were performed. Variables analyzed were lesion size, depth, and location; number of pleural passes; needle size; presence of emphysema; and training level of the person who performed the biopsy. RESULTS: Pneumothorax occurred at 144 (40.4%) of 356 biopsies, including 139 (42.0%) CT-guided and five (21%) fluoroscopically guided biopsies. Chest tube placement was needed in 25 (17.4%) of 144 cases of pneumothorax (7% of all biopsies). An increased rate of pneumothorax was correlated with smaller lesion size (P = .001) and presence of emphysema (P = .01). Patients with emphysema were three times as likely to require chest tube placement. The pneumothorax rate was 15% (16 of 105) if no aerated lung was traversed and approximately 50% if aerated lung was penetrated. Lesion location, needle size, number of pleural passes, and level of training were not correlated with pneumothorax rate. CONCLUSION: Smaller lesion size and emphysema are strongly correlated with occurrence of pneumothorax. Pneumothorax was more than three times less frequent if no aerated lung was traversed. After pneumothorax, chest tube placements were related to the presence of emphysema.

Pulmonary intravascular lymphomatosis: presentation with dyspnea and air trapping.

Intravascular lymphomatosis (IVL) is a rare lymphoid neoplasm that is typically of B-cell lineage and characterized by proliferation of malignant cells within small arterioles, capillaries, and venules. We report a patient with pulmonary IVL who presented clinically with progressive dyspnea, fever, and a dry cough. Pulmonary function tests revealed a marked decrease in diffusion capacity with airflow obstruction and severe air trapping. High-resolution CT (HRCT) of the chest with inspiratory and expiratory images revealed mosaic attenuation consistent with air trapping. Transbronchial biopsies revealed the diagnosis of IVL with capillary expansion in the alveolar and peribronchiolar interstitial tissue. IVL should be considered in the differential diagnosis of a patient with an interstitial lung disease, air trapping on pulmonary function tests, and mosaic attenuation on HRCT. Transbronchial biopsies may be the initial diagnostic procedure of choice.

The thermodilution technique for measuring resting energy expenditure does not agree with indirect calorimetry for the critically ill patient.

BACKGROUND: The complications associated with overfeeding critically ill patients are well documented. Indirect calorimetry is touted as the gold standard for measuring resting energy expenditure (REE). Unfortunately, the device is expensive, and many centers do not have this technology. The thermodilution technique for measuring cardiac output and calculating REE using the Fick equation has been reported to be an acceptable alternative. This study compared these techniques in a critically ill population. METHODS: Forty consecutive patients with indwelling Swan-Ganz catheters in the surgical intensive care unit were prospectively studied while under the consultative care of the nutrition support service. REE was determined in all patients by both techniques within a 2-hour period. An error of 5% (approximately+/-100 kcal/d) between the two methods was deemed acceptable for clinical use. RESULTS: Mean values for REE were 1928+/-558 vs 1898+/-518 kcal/d for the indirect calorimetry and thermodilution methods, respectively, and were not significantly different. However, there was great variation between the two techniques for the majority of patients such that REE determinations did not agree (t = 6.8; p < .0005). In 70% of the patients, REE determinations differed by > or =20% and in 10% of the patients by 50%. Additionally, the greater the difference between the two methods, the more the thermodilution method tended to overestimate REE. CONCLUSIONS: When compared with indirect calorimetry in a critically ill population, the thermodilution method demonstrated an intersubject variability that is unacceptable for clinical use.

Cholecystokinin satiety involves CCKA receptors perfused by the superior pancreaticoduodenal artery.

Three experiments compared the potency of the type A cholecystokinin (CCKA)-receptor antagonist devazepide for increasing intake of 30% sucrose when injected into the superior pancreaticoduodenal (SPD) artery (SPD group) or jugular vein (IV group). In experiment 1, 15 min of sucrose intake in adult, male Sprague-Dawley rats after 6 h of food deprivation was increased by devazepide (20 micrograms/kg) administered into the SPD artery whether given alone or in conjunction with cholecystokinin octapeptide (CCK-8, 2 micrograms/kg ip). Devazepide had no effect in the IV group. In experiment 2, injection of 8, 20, and 50 micrograms/kg of devazepide into the SPD artery increased sucrose intake of nondeprived rats. Only the highest dose was effective in the IV group. On subsequent tests, administration of 1 microgram/kg of CCK-8 significantly suppressed intake only in the SPD group. In experiment 3, nondeprived rats with SPD artery and jugular vein catheters were tested in a within-subjects design. Devazepide (20 micrograms/kg) increased sucrose intake after injection into the SPD artery, but not into the jugular vein. In experiment 4, intraduodenal devazepide (8, 20, and 50 micrograms/kg) had no effect. These results indicate that CCKA receptors within the SPD arterial bed mediate the satiating action of CCK, consistent with local action of duodenal CCK.

Pulmonary artery sarcomas: a review of clinical and radiologic features.

Primary pulmonary artery sarcomas are rare tumors that are frequently misdiagnosed as chronic pulmonary emboli. We present classic imaging findings and review data from 136 previously reported sarcomas. We believe that the imaging findings can be quite specific, especially when the disease is advanced. Despite a recent increase in antemortem diagnosis, the prognosis remains poor. Surgery prolongs survival time and is potentially curative. Experience with adjuvant chemotherapy and radiotherapy is limited.

Sand aspiration with near-drowning. Radiographic and bronchoscopic findings.

Sand and foreign-body aspiration may accompany drowning and near-drowning, but few details regarding such patients are available in the literature. We report a 26-yr-old woman who suffered near-drowning after a motor-vehicle accident. Initial attempts at ventilation were compromised by increased peak airway pressures, which decreased following the removal of large amounts of sand from the patient's endotracheal tube. Chest radiographs and computed tomographic (CT) scans of the patient obtained upon her arrival in the emergency department demonstrated sand bronchograms within the lower lobes of both lungs, and sand within the maxillary sinuses and stomach. We present the radiographic, bronchoscopic, and microbiologic findings within hours after this patient's accident, with a review of the literature and provisional recommendations for the management of such patients.

Identification of tobacco-specific carcinogen in the cervical mucus of smokers and nonsmokers.

BACKGROUND: In 1996, an estimated 15,700 new cases of cancer of the uterine cervix and 4,900 deaths from this disease were expected to occur in the United States. In a recent international study, human papillomavirus DNA was found in more than 90% of cervical tumor specimens examined, irrespective of the nationality of the patients from whom the samples were obtained. Although infection with human papillomavirus is the major known risk factor for the development of cervical cancer, it alone is not sufficient. Other etiologic factors that have been associated with this disease include deficiencies in micronutrients, lower socioeconomic status, oral contraceptive use, and cigarette smoking. Several compounds from cigarette smoke (nicotine and its major metabolite, cotinine) have been identified in cervical mucus, and the occurrence of smoking-related DNA damage in the cervical epithelium has been documented. PURPOSE: This investigation was conducted to determine for the first time whether carcinogenic tobacco-specific N-nitrosamines are present in the cervical mucus of cigarette smokers and of nonsmokers (most likely as a result of environmental exposure). METHODS: Cervical mucus specimens from 15 smokers and 10 nonsmokers were subjected to supercritical fluid extraction with the use of carbon dioxide that contained 10% methanol, and the resultant extracts were analyzed for tobacco-specific nitrosamines by use of a very sensitive method that involved gas chromatography and mass spectroscopy analyses. RESULTS: In a total of 16 samples obtained from 15 women who were current smokers (two samples from the same woman), we detected the tobacco-specific nitrosamine 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) at concentrations that ranged from 11.9 to 115.0 ng/g of mucus. Only one of a total of 10 cervical mucus specimens obtained from 10 women who claimed to be nonsmokers did not contain detectable NNK, and NNK concentrations ranged from 4.1 to 30.8 ng/g of mucus in the specimens from the remaining nine women. The concentrations of NNK in specimens from cigarette smokers were significantly higher than those from nonsmokers (mean +/- standard deviation: 46.9 +/- 32.5 ng/g of mucus versus 13.0 +/- 9.3 ng/g of mucus; two-tailed Student's t test, P = .004). CONCLUSION: The cervical mucus of cigarette smokers contains measurable amounts of the potent carcinogen NNK. This compound represents the first tobacco-specific carcinogen identified in this physiologic fluid of women who smoke cigarettes. The presence of NNK in the cervical mucus of nonsmokers is likely due to environmental exposure or to the fact that some of the subjects in this study may not have revealed that they occasionally smoked cigarettes. IMPLICATIONS: The presence of NNK in human cervical mucus further strengthens the association between cervical cancer and tobacco smoking.

Localized benign fibrous tumors of the pleura: MR appearance.

PURPOSE: Our goal is to describe the MR findings in benign localized fibrous tumors of the pleura. METHOD: Chest radiographs, CT scans, and MR images of four patients with localized benign fibrous tumors of the pleura were retrospectively reviewed and correlated with the pathologic findings. RESULTS: Tumors ranged from 4 to 18 cm in their largest diameter. Three tumors were located in the diaphragmatic region, and one was within the left major fissure. All tumors were round to ovoid, pedunculated, and well delineated. On T1-weighted SE MR images, tumors showed low signal intensity. All tumors had heterogeneous but predominantly low signal intensity on proton-density-weighted images and lower signal intensity on T2-weighted images. CONCLUSION: Localized benign fibrous tumors of the pleura were characterized by low signal intensity on all MR sequences that is explained by high collagen content within the tumors' stroma and should suggest the diagnosis preoperatively.

CCK-8 activates hepatic vagal C-fiber afferents.

Intravenous administration of 2 micrograms/kg CCK-8 increased the single unit activity of 54% of hepatic vagal afferent fibers. Conduction velocity tests indicated that all of these units were C fibers. The increase in hepatic vagal activity produced by CCK-8 was significantly reduced by i.v. administration of 200 micrograms/kg of the CCKA receptor antagonist devazepide. Control comparisons indicated that this reduction was not an artifact of tachyphylaxis resulting from repeated administration of CCK-8. Further, the inability of pretreatment with atropine and hexamethonium to reduce the increases in hepatic vagal activity produced by CCK-8 suggests that the latter effect was not secondary to changes in gastrointestinal motor function. These outcomes demonstrate that activation of CCKA receptors by CCK-8 increases hepatic vagal afferent activity and support the view that the duodenal satiety action of CCK is mediated by the hepatic branch.