The vector ecology of introduced Culex quinquefasciatus populations, and implications for future risk of West Nile virus emergence in the Galápagos archipelago.

Culex quinquefasciatus Say (Diptera: Culicidae), an important vector of West Nile virus (WNV) in the U.S.A., was first detected on the Galápagos Islands (Ecuador) in the 1980s. However, little is known of its ecology, distribution or capacity for arbovirus transmission in the Galápagos. We characterize details of lifecycle (including gonotrophic period), temporal abundance, spatial distribution, vector competence and host-feeding behaviour. Culex quinquefasciatus was detected on five islands of the Galápagos during 2006-2011. A period of 7-14 days was required for egg-adult emergence; water salinity above 5 ppt was demonstrated to hinder larval development. Blood-meal analysis indicated feeding on reptiles, birds and mammals. Assessment of WNV vector competency of Galápagos C. quinquefasciatus showed a median infectious dose of 7.41 log10 plaque-forming units per millilitre and evidence of vertical transmission (minimal filial infection rate of 3.7 per 1000 progeny). The distribution of C. quinquefasciatus across the archipelago could be limited by salt intolerance, and its abundance constrained by high temperatures. Feeding behaviour indicates potential to act as a bridge vector for transmission of pathogens across multiple taxa. Vertical transmission is a potential persistence mechanism for WNV on Galápagos. Together, our results can be used for epidemiological assessments of WNV and target vector control, should this pathogen reach the Galápagos Islands.

Effects of intraoperative and early postoperative normal saline or Plasma-Lyte 148® on hyperkalaemia in deceased donor renal transplantation: a double-blind randomized trial.

BACKGROUND: Administration of saline in renal transplantation is associated with hyperchloraemic metabolic acidosis, but the effect of normal saline (NS) on the risk of hyperkalaemia or postoperative graft function is uncertain. METHODS: We compared NS with Plasma-Lyte 148® (PL) given during surgery and for 48 h after surgery in patients undergoing deceased donor renal transplantation. The primary outcome was hyperkalaemia within 48 h after surgery. Secondary outcomes were need for hyperkalaemia treatment, change in acid-base status, and graft function. RESULTS: Twenty-five subjects were randomized to NS and 24 to PL. The incidence of hyperkalaemia in the first 48 h after surgery was higher in the NS group; 20 patients (80%) vs 12 patients (50%) in the PL group (risk difference: 0.3; 95% confidence interval: 0.05, 0.55; P=0.037). The mean (sd) peak serum potassium was NS 6.1 (0.8) compared with PL 5.4 (0.9) mmol litre-1 (P=0.009). Sixteen participants (64%) in the NS group required treatment for hyperkalaemia compared with five (21%) in the PL group (P=0.004). Participants receiving NS were more acidaemic [pH 7.32 (0.06) vs 7.39 (0.05), P=0.001] and had higher serum chloride concentrations (107 vs 101 mmol litre-1, P<0.001) at the end of surgery. No differences in the rate of delayed graft function were observed. Subjects receiving PL who did not require dialysis had a greater reduction in creatinine on day 2 (P=0.04). CONCLUSIONS: Compared with PL, participants receiving NS had a greater incidence of hyperkalaemia and hyperchloraemia and were more acidaemic. These biochemical differences were not associated with adverse clinical outcomes. CLINICAL TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry: ACTRN12612000023853.

A pilot study of the relationship between Doppler-estimated carotid and brachial artery flow and cardiac index.

We measured carotid and brachial artery blood flow by Doppler ultrasound in 11 human volunteers, and related these to cardiac index and to each other. The median (IQR [range]) carotid arterial blood flow was 0.334 (0.223-0.381 [0.052-0.563]) l.min(-1) on the right and 0.315 (0.223-0.369 [0.061-0.690]) l.min(-1) on the left. The brachial arterial blood flow was 0.049 (0.033-0.062 [0.015-0.204]) l.min(-1) on the right and 0.039 (0.027-0.054 [0.011-0.116]) on the left. Cardiac index was 3.2 (2.8-3.5 [1.9-5.4]) l.min(-1) .m(-2) . There was a moderate to good correlation between right-and left-sided flows (brachial: ρ = 0.45; carotid: ρ = 0.567). Brachial and carotid flow had no or a negative correlation with cardiac index (right brachial: ρ = -0.145, left brachial: ρ = -0.349; right carotid: ρ = -0.376, left carotid: ρ = -0.285). In contrast to some previous studies, we found that Doppler-estimated peripheral arterial blood flows only show a weak correlation with cardiac index and cannot be used to provide non-invasive estimates of cardiac index in man.

Potential role for extracorporeal membrane oxygenation cardiopulmonary resuscitation (E-CPR) during in-hospital cardiac arrest in Australia: A nested cohort study.

Objective: This study aims to evaluate the characteristics and outcomes of patients who fulfilled extracorporeal membrane oxygenation cardiopulmonary resuscitation (E-CPR) selection criteria during in-hospital cardiac arrest (IHCA). Design: This is a nested cohort study. Setting: Code blue data were collected across seven hospitals in Australia between July 2017 and August 2018. Participants: Participants who fulfilled E-CPR selection criteria during IHCA were included. Main outcome measures: Return of spontaneous circulation and survival and functional outcome at hospital discharge. Functional outcome was measured using the modified Rankin scale, with scores dichotomised into good and poor functional outcome. Results: Twenty-three (23/144; 16%) patients fulfilled E-CPR selection criteria during IHCA, and 11/23 (47.8%) had a poor outcome. Patients with a poor outcome were more likely to have a non-shockable rhythm (81.8% vs. 16.7%; p = 0.002), and a longer duration of CPR (median 12.5 [5.5, 39.5] vs. 1.5 [0.3, 2.5] minutes; p < 0.001) compared to those with a good outcome. The majority of patients (18/19 [94.7%]) achieved sustained return of spontaneous circulation within 15 minutes of CPR. All five patients who had CPR >15 minutes had a poor outcome. Conclusion: Approximately one in six IHCA patients fulfilled E-CPR selection criteria during IHCA, half of whom had a poor outcome. Non-shockable rhythm and longer duration of CPR were associated with poor outcome. Patients who had CPR for >15 minutes and a poor outcome may have benefited from E-CPR. The feasibility, effectiveness and risks of commencing E-CPR earlier in IHCA and among those with non-shockable rhythms requires further investigation.

The Distribution, Seasonal Abundance, and Environmental Factors Contributing to the Presence of the Asian Longhorned Tick (Haemaphysalis longicornis, Acari: Ixodidae) in Central Appalachian Virginia.

Over the past decade, Haemaphysalis longicornis, the Asian longhorned tick, has undergone a geographic range expansion in the United States, from its historical range in east Asia. This tick has been characterized by its frequent parasitism of livestock, an ability to reproduce through parthenogenesis, and its ability to transmit a variety of vector-borne pathogens to livestock, wildlife, and human hosts in its native geographic range. Thus far in the United States, 17 states have reported H. longicornis populations, including 38 counties in Virginia. These numbers come from presence-absence reports provided to the U.S. Department of Agriculture, but little has been reported about this ticks' seasonality in Virginia or its habitat preferences. Our current study detected H. longicornis populations in seven of the nine surveyed counties in Virginia. Haemaphysalis longicornis were observed in multiple habitat types including mixed hardwood forests and pastures, with abundant H. longicornis populations detected at one particular pasture site in Wythe County. This study also attempted to investigate environmental conditions that may be of importance in predicting tick presence likelihood. While sample size limited the scope of these efforts, habitat type and climatic metrics were found to be important indicators of H. longicornis collection success and abundance for both the nymphal and larval life stages. This current study reports useful surveillance data for monitoring these tick populations as they become established in the western half of Virginia and provides insight into their current distribution and maintenance over a large study region.

Oxygen administration and monitoring for ward adult patients in a teaching hospital.

AIM: The aims of this study were to describe oxygen administration and respiratory monitoring of ward patients in a tertiary teaching hospital, and to assess differences in characteristics and outcomes between patients who are receiving versus are not receiving oxygen. METHODS: Prospective clinical audit of all non-ventilated adult ward patients in a tertiary teaching hospital in Melbourne, Victoria on 26 August 2009. RESULTS: All 323 eligible patients were audited (medical 218, surgical 105). At assessment, 76 patients (24%) were on oxygen therapy and of these, 57 patients (74%) received oxygen by nasal prongs. Overall, oxygen saturation was documented in 301 (93.2%) patients and respiratory rate (RR) documented in 283 patients (87.6%). Patients receiving oxygen had a lower median SpO(2) (94% vs 96%, P < 0.0001), higher median RR (20/min vs 18/min, P < 0.0005); and were older (68.8 v 63.1 years, P= 0.0094). The in-hospital mortality of patients receiving oxygen therapy was 15.8% compared with 5.3% for those not on oxygen (P < 0.0056). CONCLUSION: Oxygen is administered to one-quarter of ward patients in our hospital. Oxygen saturation and RR are not documented in approximately 10% of patients. Oxygen therapy in ward patients identifies individuals with increased mortality. Continuing educational interventions to increase awareness of the high-risk status of these patients and strategies to detect patients at risk of hypoxaemia are needed.

Survival and functional outcome at hospital discharge following in-hospital cardiac arrest (IHCA): A prospective multicentre observational study.

AIM: To evaluate the functional outcome of patients after in-hospital cardiac arrest (IHCA) and to identify associations with good functional outcome at hospital discharge. METHOD: Emergency calls were prospectively screened and data collected for IHCAs in seven Australian hospitals. Patients were included if aged > 18 years, admitted as an acute care hospital in-patient and experienced IHCA; defined by a period of unresponsiveness with no observed respiratory effort and commencement of external cardiac compressions. Data collected included patient demographics, clinical and cardiac arrest characteristics, survival and functional outcome at hospital discharge using the modified Rankin Scale (mRS) and Katz Index of Independence in ADLs (Katz-ADL). RESULTS: 152 patients suffered 159 IHCAs (male 66.4%; mean age 70.2 (± 13.9) years). Sixty patients (39.5%) survived, of whom 43 (71.7%) had a good functional outcome (mRS ≤ 3) and 38 (63.3%) were independent with activities of daily living (ADLs) at hospital discharge (Katz-ADL = 6). Younger age (OR 0.95; 95% CI 0.91-0.98; p = 0.003), shorter duration of CPR (OR 0.84; 95% CI 0.77-0.91; p < 0.0001) and shorter duration of hospital admission prior to IHCA (OR 0.96; 95% CI 0.93-0.998; p = 0.04) were independently associated with a good functional outcome at hospital discharge. CONCLUSION: The majority of survivors had a good functional outcome and were independent with their ADLs at hospital discharge. Factors associated with good functional outcome at hospital discharge were identified.

Non-invasive estimation of cardiac index in healthy volunteers.

The primary objective was to non-invasively measure the cardiac index (CI) and associated haemodynamic parameters of healthy volunteers and their changes with age. This was a single centre, prospective, observational study of healthy volunteers aged between 20 and 59 years, using the ClearSight™ (Edwards Life Sciences, Irvine, CA, USA) device. We recorded 514 observations in 97 participants. The mean CI was 3.5 l/min/m2 (95% confidence interval [95% CI] 3.4 to 3.7 l/min/m2). The mean stroke volume index (SVI) was 47 ml/m2 (95% CI 45 to 49 ml/m2) and the mean systemic vascular resistance index was 2,242 dyne.s/cm5/m2 (95% CI 2,124 to 2,365 dyne.s/cm5/m2). There was an inverse linear relationship between increasing age and CI (P <0.0001), which decreased by 0.044 l/min/m2 (95% CI  -0.032 to -0.056 l/min/m2) per year. This change was mostly due to a decrease in SVI of 0.45 ml/m2 (95% CI 0.32 to 0.57 ml/m2) per year (P <0.0001). The mean CI of young healthy humans is approximately 3.5 l/min/m2 and declines by approximately 40 ml/min/m2 per year, mostly due to a decline in stroke volume (SV). These findings have significant implications regarding the clinical interpretation of haemodynamic parameters and the application of these results to individual patients.

A two centre observational study of simultaneous pulse oximetry and arterial oxygen saturation recordings in intensive care unit patients.

The influence of variables that might affect the accuracy of pulse oximetry (SpO2) recordings in critically ill patients is not well established. We sought to describe the relationship between paired SpO2/SaO2 (oxygen saturation via arterial blood gas analysis) in adult intensive care unit (ICU) patients and to describe the diagnostic performance of SpO2 in detecting low SaO2 and PaO2. A paired SpO2/SaO2 measurement was obtained from 404 adults in ICU. Measurements were used to calculate bias, precision, and limits of agreement. Associations between bias and variables including vasopressor and inotrope use, capillary refill time, hand temperature, pulse pressure, body temperature, oximeter model, and skin colour were estimated. There was no overall statistically significant bias in paired SpO2/SaO2 measurements; observed limits of agreement were +/-4.4%. However, body temperature, oximeter model, and skin colour, were statistically significantly associated with the degree of bias. SpO2 <89% had a sensitivity of 3/7 (42.9%; 95% confidence intervals, CI, 9.9% to 81.6%) and a specificity of 344/384 (89.6%; 95% CI 86.1% to 92.5%) for detecting SaO2 <89%. The absence of statistically significant bias in paired SpO2/SaO2 in adult ICU patients provides support for the use of pulse oximetry to titrate oxygen therapy. However, SpO2 recordings alone should be used cautiously when SaO2 recordings of 4.4% higher or lower than the observed SpO2 would be of concern. A range of variables relevant to the critically ill had little or no effect on bias.

Effect of N-methyl-N'-nitro-N-nitrosoguanidine on gastroduodenal epithelial proliferation in Wistar/Lewis rats.

The effect of N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) on gastroduodenal epithelial proliferation p]rior to the development of frank neoplasia was studied in inbred LEW rats with or without gastric ulcers. The rats received either MNNG (100 gm/liter) in the drinking water or plain water. After 4 weeks, some rats in the MNNG-treated and control groups were given injections of tritiated thymidine and killed 1 hour later. In other rats, either an ulcer of the fundic mucosa was formed by a suction biopsy tube at laparotomy or a sham operation was performed. At 2 and 4 weeks after the operation, these rats were given injections of tritiated thymidine and killed 1 hour later. Sections of fundus, antrum, and duodenum were prepared for light autoradiography. MNNG treatment stimulated gastroduodenal epithelial proliferation, expanded the proliferative zone (PZ), and in the duodenum caused marked villus blunting and elongation of the crypts. No additional effect of the fundic ulcer or sham operation on gastroduodenal proliferation could be determined. The MNNG-induced expansion of the PZ occurred in a downward direction. Thus theories of carcinogenesis should include not only the expansion of the PZ toward the mucosal surface but also the possibility of expansion of the PZ toward the base of the mucosa.

A feasibility study of functional status and follow-up clinic preferences of patients at high risk of post intensive care syndrome.

After prolonged mechanical ventilation patients may experience the 'post intensive care syndrome' (PICS) and may be candidates for post-discharge follow-up clinics. We aimed to ascertain the incidence and severity of PICS symptoms in patients surviving prolonged mechanical ventilation and to describe their views regarding follow-up clinics. In a teaching hospital, we conducted a cohort study of all adult patients discharged alive after ventilation in ICU for ≥7 days during 2013. We administered the EuroQol-5D (EQ-5D) and Hospital Anxiety and Depression Scale (HADS) via telephone interview and asked patients their views about the possible utility of a follow-up clinic. We studied 48 patients. At follow-up (average 19.5 months), seven (15%) patients had died and 14 (29%) did not participate (eight declined; two were non-English speakers; four were non-contactable). Among the 27 responders, 16 (59%) reported at least moderate problems in ≥1 EQ-5D dimension; 10 (37%) in ≥2 dimensions, and 8 (30%) in ≥3 dimensions. Moreover, 10 (37%) patients reported marked psychological symptoms; six (22%) scored borderline or abnormal on the HADS for both anxiety and depression; and four (15%) scored borderline or abnormal for one component. Finally, 21/26 (81%) patients stated that an ICU follow-up clinic would have been beneficial. At long-term follow-up, the majority of survivors of prolonged mechanical ventilation reported impaired quality of life and significant psychological symptoms. Most believed that a follow-up clinic would have been beneficial.

Intravenous fluid bolus therapy: a bi-national survey of critical care nurses' self-reported practice.

Knowledge of critical care nurses' intravenous fluid bolus therapy (FBT) practice remains underexplored. Using a multi-choice online survey conducted between September and October 2014, we sought to describe the self-reported practice of critical care nurses located in Australia and New Zealand. Two hundred and ninety-five critical care nurses responded to the survey with most practising in adult ICUs. Overall, 0.9% saline solution was the preferred solution for FBT. However, more Australian than New Zealand respondents preferred 'albumin 4%' (31% versus 3.6%, P <0.01) for FBT. In contrast, more New Zealand respondents preferred 'Plasma-Lyte®' (33.3% versus 6.4%, P <0.01). Half of the respondents defined FBT as 250 ml administered as quickly as possible. However, FBT volumes ranged from 100 ml to >1000 ml and administration duration from as quickly as possible to 60 minutes. In response to FBT, almost half of the respondents expected an increase in mean arterial pressure of between 11 to 20 mmHg. Similarly, >40% expected a central venous pressure increase >3 mmHg, >70% expected a urinary output increase of 0.5 to 1.0 ml/kg/hr, and >60% expected a decrease in heart rate of >11 /min. Overall, 0.9% saline remains the most common solution for FBT, but there are significant national differences in the preference for albumin and Plasma-Lyte. A volume of 250 ml defines a fluid bolus, with a range from 100 ml to >1000 ml, and speed of delivery from stat to 60 minutes. Most nurses expect substantial physiological effects with FBT.

The effect of augmenting early nutritional energy delivery on quality of life and employment status one year after ICU admission.

Augmenting energy delivery during the acute phase of critical illness may reduce mortality and improve functional outcomes. The objective of this sub-study was to evaluate the effect of early augmented enteral nutrition (EN) during critical illness, on outcomes one year later. We performed prospective longitudinal evaluation of study participants, initially enrolled in The Augmented versus Routine approach to Giving Energy Trial (TARGET), a feasibility study that randomised critically ill patients to 1.5 kcal/ml (augmented) or 1.0 kcal/ml (routine) EN administered at the same rate for up to ten days, who were alive at one year. One year after randomisation Short Form-36 version 2 (SF-36v2) and EuroQol-5D-5L quality of life surveys, and employment status were assessed via telephone survey. At one year there were 71 survivors (1.5 kcal/ml 38 versus 1.0 kcal/ml 33; P=0.55). Thirty-nine (55%) patients consented to this follow-up study and completed the surveys (n = 23 and 16, respectively). The SF-36v2 physical and mental component summary scores were below normal population means but were similar in 1.5 kcal/ml and 1.0 kcal/ml groups (P=0.90 and P=0.71). EuroQol-5D-5L data were also comparable between groups (P=0.70). However, at one-year follow-up, more patients who received 1.5 kcal/ml were employed (7 versus 2; P=0.022). The delivery of 1.5 kcal/ml for a maximum of ten days did not affect self-rated quality of life one year later.

The epidemiology of sepsis during rapid response team reviews in a teaching hospital.

In a three-month retrospective study, we assessed the proportion of rapid response team (RRT) calls associated with systemic inflammatory response syndrome (SIRS) and sepsis. We also documented the site of infection (whether it was community- or hospital-acquired), antibiotic modifications after the call and in-hospital outcomes. Amongst 358 RRT calls, two or more SIRS criteria were present in 277 (77.4%). Amongst the 277 RRT calls with SIRS criteria, 159 (57.4%) fulfilled sepsis criteria in the 24 hours before and 12 hours after the call. There were 118 of 277 (42.6%) calls with SIRS criteria but no evidence of sepsis and 62 of 277 (22.3%) calls associated with both criteria for sepsis as well as an alternative cause for SIRS. Hence, 159 (44.4%) of all 358 RRT calls over the three-month study period fulfilled criteria for sepsis and in 97 (159-62) (27.1%) of the 358 calls, there were criteria for sepsis without other causes for SIRS criteria. The most common sites of infection were respiratory tract (86), abdominal cavity (38), urinary tract (26) and bloodstream (26). Infection was hospital-acquired in 91 (57.2%) and community-acquired in 67 (42.1%) cases, respectively. Patients were on antibiotics in 127 of 159 (79.9%) cases before the RRT call and antibiotics were added or modified in 76 of 159 (47.8%) cases after RRT review. The hospital length-of-stay of patients who received an RRT call associated with sepsis was longer than those who did not (16.0 [8.0 to 28.5] versus 10 days [6.0 to 18.0]; P=0.002).

Urinary neutrophil gelatinase-associated lipocalin to hepcidin ratio as a biomarker of acute kidney injury in intensive care unit patients.

BACKGROUND: Labile iron is important in the pathogenesis of acute kidney injury (AKI). Neutrophil gelatinase-associated lipocalin (NGAL) and hepcidin control iron metabolism and are upregulated during renal stress. However, higher levels of urinary NGAL are associated with AKI severity whereas higher urinary hepcidin levels are associated with absence of AKI. We aimed to investigate the value of combining both biomarkers to estimate the severity and progression of AKI in intensive care unit (ICU) patients. METHODS: Urinary NGAL and hepcidin were quantified within 48 hours of ICU admission in patients with the systemic inflammatory response syndrome and early kidney dysfunction (oliguria for ≥ 2 hours and/or a 25 µmol/L creatinine rise from baseline). Diagnostic and prognostic characteristics were assessed by logistic regression and receiver operating characteristics (ROC) analysis. RESULTS: Of 102 patients, 26 had mild AKI and 28 patients had severe AKI on admission. Sepsis (21%), cardiac surgery (17%) and liver failure (9%) were primary admission diagnoses. NGAL increased (P=0.03) whereas hepcidin decreased (P=0.01) with increasing AKI severity. The value of NGAL/hepcidin ratio to detect severe AKI was higher than when NGAL and hepcidin were used individually and persisted after adjusting for potential confounders (adjusted OR 2.40, 95% CI 1.20-4.78). The ROC areas for predicting worsening AKI were 0.50, 0.52 and 0.48 for NGAL, 1/hepcidin and the NGAL/hepcidin ratio. CONCLUSION: The NGAL/hepcidin ratio is more strongly associated with severe AKI than the single biomarkers alone. NGAL and hepcidin, alone or combined as a ratio, were unable to predict progressive AKI in this selected ICU cohort.

Effects of sucralfate, lansoprazole, and cimetidine on the delayed healing by hydrocortisone sodium phosphate of chronic gastric ulcers in the rat.

We have previously shown that chronic sucralfate ingestion stimulates gastric epithelial proliferation in rats, which may explain one of the beneficial effects of sucralfate in healing of peptic ulcers. In a separate study, we have found that chronic steroid administration delays the healing of experimental gastric ulcers in rats. This study was designed to test the beneficial effects of sucralfate, cimetidine, and lansoprazole (AG-1749, a new proton pump inhibitor), on the delayed healing by steroids in rat chronic gastric ulcers. Chronic gastric ulcers were produced in male Wistar rats, weighing 180 g, by the application of 100% acetic acid. The rats were randomly divided into five groups; (1) control, (2) vehicle alone, (3) 10 mg/kg lansoprazole, (4) 500 mg/kg sucralfate, and (5) 100 mg/kg cimetidine. Except for controls, all rats received daily intraperitoneal injections of 2.5 mg/kg hydrocortisone sodium phosphate. Tested drugs were administered intragastrically (lansoprazole and sucralfate) or intraperitoneally (cimetidine) twice a day for 2 weeks. Rats were sacrificed 14 days later and ulcer size was measured. Chronic administration of hydrocortisone sodium phosphate resulted in a significant delay of ulcer healing induced by acetic acid. Treatment with either lansoprazole or sucralfate abolished the deleterious effect of steroids, whereas cimetidine had no effect. These results indicate that lansoprazole and sucralfate overcome the delayed healing by steroids of chronic gastric ulcers in the rat.

Small bowel morphology and epithelial proliferation in intravenously alimented rabbits.

Intravenous (IV) alimentation of experimental animals has been associated with an attenuation of the small bowel mucosa. To determine whether alterations in epithelial renewal accompany the morphological changes, we studied cell proliferation as well as the light and electron microscopic appearance of the small bowel in intravenously and orally alimented rabbits. After 10 days of either IV or oral alimentation, 3H-thymidine was given intravenously to all animals to label proliferating cells, and 1 hour later sections of duodenum, upper jejunum, and distal ileum were taken for autoradiography and light and electron microscopy. IV alimentation was accompanied by significant reductions in epithelial cell proliferation and mucosal thickness in the proximal small bowel. The density of goblet cells was greater in the duodenum and jejunum, but less in the ileum, of intravenously alimented rabbits than in corresponding areas of the oral controls. Furthermore, ultrastructural changes in the villous absorptive cells of intravenously alimented rabbits, such as lengthened microvilli and increased numbers of multivesicular bodies, suggested that epithelial migration also may be slowed during IV alimentation.

Pancreatic polypeptide causes diarrhea and weight loss in obese mice but not in lean littermates.

Pancreatic polypeptide was infused into obese-hyperglycemic (ob/ob) mice and lean littermates to determine its effect on weight gain. Obese mice continuously infused with 30, 60, or 100 micrograms/day for 7 days developed both diarrhea and weight loss in a dose dependent fashion. Lean littermates infused with 100 micrograms/day developed neither diarrhea nor weight loss. Light microscopic study of ileum and colon revealed no abnormalities. These studies indicate that the effects of pancreatic polypeptide are in part genetically determined since the obese and non-obese mice differ at only one gene locus.

Plasma levels of human neurotensin: methodological and physiological considerations.

The ingestion of a meal high in fat content is known to increase circulating levels of neurotensin (NT) in humans. However, the magnitude of the postprandial rise of NT in the general circulation and its physiological significance have been subject of much debate. The present study examines circulating levels of NT in male volunteers prior to and following each of their three daily meals (ca. 31 g fat/meal). The response observed are also compared to that elicited by the direct instillation of intralipid (ca. 44 g fat) into the duodenum. NT levels were determined by radioimmunoassay of acid/acetone extracted plasma fractionated by high pressure liquid chromatography. Meals caused a significant but modest increase in NT levels, with the largest increment (ca. 4 fmol/ml) occurring after breakfast. In contrast, NT levels increased ca. 20 fmol/ml with intraduodenal instillation of lipid. The meal-stimulated increases in circulating NT measured here are 4- to 5-fold less than those reported by others, the difference most likely reflecting the lesser amount of lipid ingested. Previous studies provided subjects with single meals containing in excess of 120 g of fat; the 30 g of fat ingested by our subjects, ca. 33% of total caloric intake, is near that recommended by the U.S. Senate, Select Committee on Nutritional and Human Needs. These data show that diets with a reasonable fat content have only a modest effect on circulating levels of NT.

Hydrocortisone has a biphasic effect on rat gastric mucosal prostaglandin generation in vivo: inhibition at low doses, stimulation at high doses.

To determine the effect of different doses of hydrocortisone sodium succinate (HC) on rat gastric mucosal prostaglandin synthesis, two experiments were performed. In the first experiment, 20 male Lewis rats were divided into 4 groups of 5 rats each and gavaged either with 2 ml of water (control) or different concentrations of HC (10 mg/ml, 100 mg/ml and 500 mg/ml). In the second experiment in a similar design, lower doses of HC were used (water, 0.1 mg/ml, 0.50 mg/ml and 5.0 mg/ml). The rats were killed after 1 h and three 3 x 3 mm pieces of gastric tissue were removed from each rat and incubated for the determination of prostaglandin E2 and 6-keto-prostaglandin F1 alpha accumulation in the medium measured by radioimmunoassay. At low doses HC inhibits rat gastric mucosal prostaglandin synthesis whereas at higher doses HC stimulates it. This biphasic effect of HC on gastric mucosal prostaglandin synthesis may help explain its role in ulcerogenesis.