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We report that the anorectic potency of neuromedin B (NMB) and gastrin-releasing peptide (GRP) is potentiated using a prefeed paradigm. During the light phase, adult male Sprague-Dawley rats (groups of n = 6) were given 30-min (pre-feed) access to a liquid diet. Thirty min later rats were injected i.p. with GRP or NMB (0, 8, 16, 32 or 64 micrograms kg-1) and given further access to the liquid diet. In prefed (PF) rats, high doses of NMB (32 and 64 micrograms kg-1) delayed the onset of eating in the test by10 min, significantly suppressing 30-min intake. The same doses of NMB in non prefed (NPF) rats were ineffective. Weak effects of GRP in NPF rats to reduce meal size were also enhanced under PF conditions. Exogenous GRP and NMB, in particular, appear to interact with processes stimulated by the postingestive actions of food, supporting a role for peripheral, endogenous GRP and NMB in the development of satiation and the maintenance of postprandial satiety, respectively.

A social activist with wide-ranging concern for the welfare of his society, Wole Soyinka is on record as saying that it was the death toll among students and colleagues which prompted him to become involved in road safety. These victims were among the grim statistics of accidents; for example, in 1988 a total of 9,077 people were killed on Nigerian roads, and 24,413 were injured.2 But it is clear from Soyinka's writing that his interest in ‘the road’, and the rich characters it throws up and crushes under foot, predates the slaughter of his students. Early poems such as ‘Epitaph for Say Tokyo Kid’, and prose pieces such as ‘Oga Look Properly’, testify to this, as does the work of the mid-1960s, which includes the satirical revue sketch ‘Obstacle Race’ (about the hazards facing drivers in Nigeria), his first novel, The Interpreters (London, 1965), with its memorable description of the death of Sekoni in a motor accident, and above all his play entitled The Road (London, 1965). When these are linked with Soyinka's interest in the god of the road, Ogun, it was not surprising to find a whole section of his first collection of verse described as ‘of the road’.

Objective. To determine predictors of walking velocity in the elderly. Methods. Five hundred thirty-two persons from 3 cohorts of elderly persons (retirement community, ambulatory care medical clinic, or chronically homebound population) performed a 10-foot (for the homebound subjects) or 50-foot (for all other subjects) walk time test and underwent a standardized interview, chart review, and clinical examination. The 73 independent variables that were evaluated included demographic, musculoskeletal, neurologic, psychologic, and other comorbidity items. Least-squares and least-absolute-deviation regression tree analyses were performed to determine the strongest predictive factors associated with walking velocity. Results. Sampling cohort (homebound versus non-homebound), quadriceps strength, hip flexion strength, lumbosacral spine impairment, lower joint impairment, and education were found to be associated with walking velocity. Joint pain measures were not associated with walking velocity. Conclusion. Muscle strength variables are better predictors of walking velocity than are joint pain variables. Thus, clinical trials and observational studies using walking velocity as an outcome need to take into consideration the influence of muscle strength on this outcome variable.

To determine the effects of bombesin (BN) and gastrin-releasing peptide [GRP(1-27)] on food intake and the microstructure of licking, the rate and pattern of licking were measured by lickometer after intraperitoneal administration of 2, 4, 8, and 16 micrograms/kg of each peptide. Although both peptides inhibited intake significantly, the dose-response functions of the peptides were different. At lower doses (2-4 micrograms/kg) the peptides were equipotent; at higher doses (8-16 micrograms/kg) BN was significantly more potent than GRP(1-27), possibly due to an action of BN on neuromedin B (NMB) receptors. The microstructural results demonstrated that both peptides decreased intake by increasing the rate of decay of licking and decreasing the number of bursts and clusters without changing the initial rate of licking or the size of the bursts and clusters. This combination of microstructural changes is evidence that both peptides increased the postingestive negative feedback effects of the diet without changing the orosensory positive feedback. These results are consistent with, but do not prove, the hypothesis that endogenous GRP(1-27) acts as a postingestive satiety signal in rats.

Aminoacyl-tRNA synthetases (ARSs) are critical components of protein translation, providing ribosomes with aminoacyl-tRNAs. In return, ribosomes release uncharged tRNAs as ARS substrates. Here, we show that tRNA deacylation can be uncoupled from protein synthesis in an amino acid specific manner. While tRNAs coupled to radiolabeled Met, Leu Lys, or Ser are stable in cells following translation inhibition with arsenite, radiolabeled Cys is released from tRNA at a high rate. We discuss possible translation independent functions for tRNA(Cys).

Here, we address the question of why the influenza A virus hemagglutinin (HA) does not escape immunity by hyperglycosylation. Uniquely among dozens of monoclonal antibodies specific for A/Puerto Rico/8/34, escape from H28-A2 neutralization requires substitutions introducing N-linked glycosylation at residue 131 or 144 in the globular domain. This escape decreases viral binding to cellular receptors, which must be compensated for by additional substitutions in HA or neuraminidase that enable viral replication. Sequence analysis of circulating H1 influenza viruses confirms the in vivo relevance of our findings: natural occurrence of glycosylation at residue 131 is always accompanied by a compensatory mutation known to increase HA receptor avidity. In vaccinated mice challenged with WT vs. H28-A2 escape mutants, the selective advantage conferred by glycan-mediated global reduction in antigenicity is trumped by the costs of diminished receptor avidity. These findings show that, although N-linked glycosylation can broadly diminish HA antigenicity, fitness costs restrict its deployment in immune evasion.

To investigate the functional capacity of the combination of pregastric and gastric satiating stimuli for the control of meal size, rats were surgically implanted with a pyloric cuff that could be inflated to prevent gastric emptying. After 0.5 or 19 h of food deprivation, rats were given access for 30 min to three concentrations of sucrose (0.8, 0.4, and 0.2 M) and of corn oil emulsions (100%, 50%, and 25%) in descending order. There were only two significant changes in intake between cuff-open and cuff-closed tests and both occurred after 19 h of food deprivation: 1) meal size of 50% corn oil with the cuff closed was significantly larger than meal size of 50% corn oil with the cuff open on the preceding day; 2) meal size of 0.8 M sucrose with the cuff closed was significantly larger than meal size with the cuff open on the next test day. These results provide new experimental evidence that when ingested food is prevented from emptying from the stomach acutely, the satiating effect of food stimuli acting at pregastric and gastric sites is sufficient to produce meals of normal size under many, but not all, experimental conditions.

To compare the effect of total abdominal vagotomy on the satiating potency of cholecystokinin COOH-terminal octapeptide (CCK-8) in sham feeding and real feeding, we administered CCK-8 intraperitoneally (2, 4, and 8 micrograms/kg) 1 min before a sham feeding or real feeding intake test. CCK-8 was at least as potent for inhibiting intake during sham feeding as it was during real feeding. Total abdominal vagotomy decreased the satiating potency of all three doses of CCK-8 equally in both feeding conditions. These results are consistent with the proposal that abdominal vagal afferent fibers are as necessary for the mediation of the satiating effect of CCK-8 in sham feeding as they are in real feeding.

The satiating effect of intravenous fat infusions was investigated in sham-feeding rats. Intralipid infusions at loads of 2.5-10.0 kcal were administered into either the inferior vena cava or the hepatic-portal vein during sham feeding. Intravenous infusions of Intralipid by either route had no effect on sham feeding during 60-min tests. In earlier work we found that duodenal infusions of Intralipid rapidly inhibited sham feeding and elicited behaviours typical of satiety under test conditions identical to those of the present study. The lack of effect of intravenous infusions of Intralipid on sham feeding is further evidence for a preabsorptive site of action for the satiety effect of Intralipid.

MHC class I molecules function to display peptides generated from cellular and pathogen gene products for immune surveillance by CD8 + T cells. Cells typically express ∼100,000 class I molecules, or ∼1 per 30,000 cellular proteins. Given “one protein, one peptide” representation, immunosurveillance would be heavily biased toward the most abundant cell proteins. Cells use several mechanisms to prevent this, including the predominant use of defective ribosomal products (DRiPs) to generate peptides from nascent proteins and, as we show here, compartmentalization of DRiP peptide generation to prevent competition from abundant cytosolic peptides. This provides an explanation for the exquisite ability of T cells to recognize peptides generated from otherwise undetected gene products.

Prior calculations based on ECEPP (Empirical Conformational Energies for Peptides Program) of the low energy minima for cholecystokinin (CCK) and Met-enkephalin have demonstrated that significant structural features of these two peptides are identical. This result suggested the possibility that Met-enkephalin, as well as other enkephalin analogues of similar structure, could associate with receptors for CCK. To test this theoretical result, we examined the ability of Met-enkephalin and its analogues to bind to peripheral CCK receptors in the rat gastrointestinal tract; in particular, we measured the ability of the opiate peptide to inhibit the effects of CCK in a physiological assay system which we have previously characterized: CCK-induced contraction of the isolated rat pyloric sphincter. We find that Met-enkephalin is an antagonist of the CCK-8-induced contraction, with a IC50 of 110 nM. Furthermore, antibodies against CCK were found to cross-react with Met-enkephalin and its analogues in a manner which suggests a distinct structure-activity relationship. These experimental results strongly support the theoretical results of conformational analysis showing structural similarity between enkephalin and CCK. They further suggest that enkephalins could modulate the response of CCK systems under physiological conditions.

Intracerebroventricular (ICV) bombesin increases grooming and decreases food intake in rats. We examined tolerance to these effects by administering a daily injection of either saline or 25 ng bombesin to rats for 8 days via lateral ventricular cannulas. Food intake and grooming were monitored. After 8 days bombesin no longer increased grooming or decreased food intake in bombesin-treated rats, but did increase grooming and decrease food intake in saline-treated rats. This development of behavioral tolerance conflicts with previous reports using larger doses and demonstrates that repeated small doses of ICV bombesin produce different effects from larger doses.

Cholecystokinin COOH-terminal octapeptide (CCK-8) produces a satiating effect in the rat and other animals upon peripheral administration. Although it has been demonstrated that the receptors which mediate this action are located in the periphery and are of the CCK-A subtype, their anatomical location has not been firmly established. A dense population of CCK receptors in the pyloric sphincter has been suggested as a candidate. We here quantify the potency of several CCK antagonists to inhibit the contractile effect of CCK-8 on the rat pyloric sphincter in vitro. The potent and selective antagonist MK-329 has a Schild pK of 8.85; the less potent but selective antagonist lorglumide (CR-1409) a pK of 6.37; the related antagonist phenoxyacetylproglumide (phi oAc proglumide) a pK of 5.1; and the weak parent compound proglumide a pK of about 3.3. These data can be compared with the potencies of these compounds to inhibit the actions of CCK-8 to produce satiety in the rat; this comparison supports the contention that CCK receptors of the rat pyloric sphincter could in part mediate the satiety effect produced by exogenous CCK-8.

To assess the role of cholecystokinin (CCK) receptors in mediating the satiating effect of an oral preload, overnight food-deprived rats (n=7) were given access to a high-carbohydrate liquid diet for 40 min. At the end of 40 min, food was removed and rats were injected subcutaneously (SC) with devazepide (DVZ; 1 ng/kg-1 mg/kg), an antagonist selective for the CCK-A receptor, or its vehicle, 0.5% carboxymethylcellulose (CMC). Thirty min after injection, rats were given access to the same liquid food for 60 min. DVZ increased food intake significantly. Furthermore, the effectiveness of a very low dose of DVZ (10 ng/kg) is strong evidence that the effect of DVZ was specific for CCK-A receptors. Three of the rats that increased food intake after DVZ were also tested with L-365,260, an antagonist selective for the CCK-B receptor (10 ng/kg-100 μg/kg). L365,260 did not increase food intake significantly. These results confirm and extend previous reports that CCK-A receptor blockade increases food intake after an oral preload. They do not, however, demonstrate a role for the CCK-B receptor in mediating the satiating effect of ingested food under the same experimental conditions.

To determine the type of cholecystokinin (CCK) receptor that mediates the inhibitory effects of peripherally administered CCK-8 on food intake and activity in 9- to 12-day-old rat pups, we gave injections of a type-A CCK receptor antagonist, MK-329, or of the type-B CCK receptor antagonist, L-365,260, prior to CCK-8 (IP). MK-329 reversed the inhibitory effects of CCK-8, but L-365,260 did not. This demonstrates that the inhibitory effects of CCK-8 (IP) are mediated by type-A, but not type-B, CCK receptors in pups of this age.

The satiating effect of duodenally administered fats was investigated with intraduodenal infusions of Intralipid in sham-feeding rats. Intralipid rapidly inhibited sham feeding and elicited the behavioral sequence of satiety. The satiating potency of Intralipid infusions in concentrations of 0.125-1 kcal/ml was a function of the concentration infused. The time course for Intralipid-induced satiety showed that fats inhibited feeding and led to the behavioral sequence of satiety within 15 min after the infusions began. This time course is evidence for a preabsorptive site of action to the small intestine. To test this hypothesis we added the local anesthetic tetracaine to Intralipid infusions. Tetracaine significantly reduced the satiating potency of Intralipid infusion. This result supports the hypothesis of a preabsorptive site of action. We also tested the specificity of intraduodenal Intralipid for feeding by administering Intralipid to rats that were sham drinking. The effect of Intralipid was relatively specific because the threshold concentration of Intralipid necessary to inhibit sham drinking was higher than the threshold for sham feeding. In addition, at superthreshold concentrations, Intralipid inhibited sham drinking less than sham feeding and elicited different behaviors than were observed during sham feeding.

Background The incidence of hernia accident for inguinal hernias in men who are minimally symptomatic is sufficiently low that watchful waiting is an acceptable alternative to routine repair. Our aim was to determine whether a delay in hernia surgery affects short- and long-term outcomes. Methods Patients from a multicenter randomized clinical trial of immediate tension-free repair versus watchful waiting for minimally symptomatic inguinal hernias were studied. Patients (n = 353) underwent tension-free repair and were classified as immediate repair (≤6 months, N = 288) or delayed repair (>6 months, N = 65). Results Patients were similar at baseline with respect to age, American Society of Anesthesiologists classification, pre-existing conditions, hernia type, and hernia characteristics. Patients undergoing immediate and delayed repair had comparable surgical time, surgical complications, recurrence rates, and satisfaction with outcome. Multivariate analyses found no relation between duration until hernia repair and operative time, incidence of complications, long-term pain, or functional status. Conclusions Delaying hernia repair in patients who are minimally symptomatic does not have an adverse effect on subsequent operation and on other outcomes.

Background Although inguinal hernia repair is a common and safe procedure, a significant portion of patients who undergo surgical repair experience postoperative chronic pain. We conducted a clinical trial to determine if delay of repair is a safe and acceptable alternative for men with minimally symptomatic inguinal hernias. Here we report on the effects of delay on the patient's family. Study Design Data are from a randomized trial in which men with asymptomatic or minimally symptomatic inguinal hernia were randomly assigned to either open tension-free repair (TFR) or watchful waiting (WW). Patients indicated a person who could assist them if necessary because of their hernia or hernia operation, and these persons (mostly spouses) answered a questionnaire at baseline and followup addressing concern about the patient's ability to perform home, social, and recreational activities and time spent assisting the patient with chores because of his hernia condition. Results In both intention-to-treat and as-treated analyses, at 2 years after enrollment, family members of patients assigned to WW were more likely to report concern about the patient's ability to perform the four types of activities. But a majority of respondents in both the WW and TFR groups indicated no concern about performance of any of the activities. In the as-treated analysis, family members of patients assigned to TFR who did not receive repair reported more time assisting the patient than those of TFR patients who received the assigned treatment. Conclusions The results favor repair, but the low level of concern about the patient's functioning reported for both TFR and WW patients suggests that this is not a major issue in delaying repair of inguinal hernias in minimally symptomatic men.

ContextMany men with inguinal hernia have minimal symptoms. Whether deferring surgical repair is a safe and acceptable option has not been assessed.ObjectiveTo compare pain and the physical component score (PCS) of the Short Form-36 Version 2 survey at 2 years in men with minimally symptomatic inguinal hernias treated with watchful waiting or surgical repair.Design, Setting, and ParticipantsRandomized trial conducted January 1, 1999, through December 31, 2004, at 5 North American centers and enrolling 720 men (364 watchful waiting, 356 surgical repair) followed up for 2 to 4.5 years.InterventionsWatchful-waiting patients were followed up at 6 months and annually and watched for hernia symptoms; repair patients received standard open tension-free repair and were followed up at 3 and 6 months and annually.Main Outcome MeasuresPain and discomfort interfering with usual activities at 2 years and change in PCS from baseline to 2 years. Secondary outcomes were complications, patient-reported pain, functional status, activity levels, and satisfaction with care.ResultsPrimary intention-to-treat outcomes were similar at 2 years for watchful waiting vs surgical repair: pain limiting activities (5.1% vs 2.2%, respectively; P = .52); PCS (improvement over baseline, 0.29 points vs 0.13 points; P = .79). Twenty-three percent of patients assigned to watchful waiting crossed over to receive surgical repair (increase in hernia-related pain was the most common reason offered); 17% assigned to receive repair crossed over to watchful waiting. Self-reported pain in watchful-waiting patients crossing over improved after repair. Occurrence of postoperative hernia-related complications was similar in patients who received repair as assigned and in watchful-waiting patients who crossed over. One watchful-waiting patient (0.3%) experienced acute hernia incarceration without strangulation within 2 years; a second had acute incarceration with bowel obstruction at 4 years, with a frequency of 1.8/1000 patient-years inclusive of patients followed up for as long as 4.5 years.ConclusionsWatchful waiting is an acceptable option for men with minimally symptomatic inguinal hernias. Delaying surgical repair until symptoms increase is safe because acute hernia incarcerations occur rarely.Clinical Trials RegistrationClinicalTrials.gov Identifier: NCT00263250

Background Four visual analog scales were constructed to assess sensory and affective components of operative pain. The Surgical Pain Scales (SPS) measure pain while at rest, pain during normal activities, pain during work or exercise, and pain unpleasantness. Study design Longitudinal data from 2,164 patients in a randomized trial of laparoscopic versus open hernia repair established the reliability, validity, and sensitivity to change of the SPS. Correlations and t-tests were used to determine their psychometric properties compared with the SF-36 health status instrument. Results Intraclass correlation coefficients of 0.95 for the sensory scales and 0.94 for the unpleasantness rating confirmed that the SPS produced reliable measurements. Correlations ranging from 0.44 to 0.60 between the visual analog scales and the bodily pain dimension on the SF-36 and significant differences between SPS levels for patients requiring more and less time to resume normal activities (p≤0.015 to p≤0.002) supported the validity of the scales. Clinical responsiveness was demonstrated by a 33.5-mm reduction (standard error=1.4 mm) in the mean rating on a 150-mm scale measuring pain during normal activities for patients reporting postoperative improvement on the bodily pain dimension (p≤0.0001). Conclusions The Surgical Pain Scales demonstrated excellent psychometric properties in this study population. The SPS can be used to compare pain levels between groups at a single point in time or to track change for individual patients over time or after operations. Individualized pain management interventions can be tailored based on the sensory and effective ratings.

To investigate the effect of a new, specific antagonist for bombesin receptors on the satiating action of exogenous bombesin, adult male rats were adapted to a nondeprivation test regimen with daily access to a palatable liquid food. In a prefeeding paradigm, rats received intraperitoneal injections of the bombesin receptor antagonist, BW2258U89 (6.25, 25, 50, or 100 micrograms kg-1) or vehicle 20 min before, and then a second injection of either bombesin (4 micrograms kg-1), gastrin-releasing peptide (GRP; 16 micrograms kg-1), the C-terminal octapeptide of cholecystokinin (CCK-8; 4 micrograms kg-1), or vehicle 5 min before a 2-h feeding test. BW2258U89 pretreatment antagonized the satiating actions of bombesin and GRP18-27 in a very potent, dose-related manner, but did not antagonize the satiating action of CCK-8. These differential results with BW2258U89 are consistent with prior results showing the potency of this antagonist for bombesin receptor-mediated effects in visceral systems; in addition, they demonstrate the selectivity of the compound for the satiating actions of peripherally administered bombesin and bombesin-like peptides.

We investigated the satiating potency of CCK-33 and of CCK-8 administered IP to rats prior to a 30-min food intake test using a high-carbohydrate liquid diet. CCK-33 and CCK-8 produced dose-related inhibitions of intake. The ID50s and the slopes of the dose-response functions of the two peptides were not significantly different. We conclude that CCK-33 is as potent as CCK-8 for inhibiting food intake in the rat.

To investigate the dependence of the satiating action of cholecystokinin on serotonergic function in rats, we examined the effects of systemic pretreatment with serotonin (5-HT) antagonists of varying selectivity for 5-HT receptor subtypes on suppression of food intake induced by systemic administration of cholecystokinin octapeptide (CCK-8). Mianserin, a 5-HT1C/2-selective antagonist, significantly attenuated the satiating action of CCK-8. Ketanserin, a 5-HT2 antagonist, and three 5-HT3 antagonists, MDL-72222, ICS 205-930, and ondansetron, however, had no effect on the satiating action of CCK-8. These results demonstrate that the satiating action of exogenous CCK depends on activation of 5-HT1 (probably 5-HT1C) receptors and that activation of 5-HT2 or 5-HT3 receptors is not required.

Objective To determine whether the investment in postgraduate education and training places patients at risk for worse outcomes and higher costs than if medical and surgical care was delivered in nonteaching settings. Background Data The Veterans Health Administration (VA) plays a major role in the training of medical students, residents, and fellows. Methods The database of the VA National Surgical Quality Improvement Program was analyzed for all major noncardiac operations performed during fiscal years 1997, 1998, and 1999. Teaching status of a hospital was determined on the basis of a background and structure questionnaire that was independently verified by a research fellow. Stepwise logistic regression was used to construct separate models predictive of 30-day mortality and morbidity for each of seven surgical specialties and eight operations. Based on these models, a severity index for each patient was calculated. Hierarchical logistic regression models were then created to examine the relationship between teaching versus nonteaching hospitals and 30-day postoperative mortality and morbidity, after adjusting for patient severity. Results Teaching hospitals performed 81 % of the total surgical workload and 90% of the major surgery workload. In most specialties in teaching hospitals, the residents were the primary surgeons in more than 90% of the operations. Compared with nonteaching hospitals, the patient populations in teaching hospitals had a higher prevalence of risk factors, underwent more complex operations, and had longer operation times. Risk-adjusted mortality rates were not different between the teaching and nonteaching hospitals in the specialties and operations studied. The unadjusted complication rate was higher in teaching hospitals in six of seven specialties and four of eight operations. Risk adjustment did not eliminate completely these differences, probably reflecting the relatively poor predictive validity of some of the risk adjustment models for morbidity. Length of stay after major operations was not consistently different between teaching and nonteaching hospitals. Conclusion Compared with nonteaching hospitals, teaching hospitals in the VA perform the majority of complex and high-risk major procedures, with comparable risk-adjusted 30-day mortality rates. Risk-adjusted 30-day morbidity rates in teaching hospitals are higher in some specialties and operations than in nonteaching hospitals. Although this may reflect the weak predictive validity of some of the risk adjustment models for morbidity, it may also represent suboptimal processes and structures of care that are unique to teaching hospitals. Despite good quality of care in teaching hospitals, as evidenced by the 30-day mortality data, efforts should be made to examine further the structures and processes of surgical care prevailing in these hospitals.

Objective . The primary purpose of this study was to validate risk‐adjusted surgical outcomes as indicators of the quality of surgical care at US Department of Veterans Affairs (VA) hospitals. The secondary purpose was to validate the risk‐adjustment models for screening cases for quality review. Design . We compared quality of care, determined by structured implicit chart review, for patients from hospitals with higher and lower than expected operative mortality and morbidity (hospital‐level tests) and between patients with high and low predicted risk of mortality and morbidity who died or developed complications (patient‐level tests). Subjects . 739 general, peripheral vascular and orthopedic surgery cases sampled from the 44 VA hospitals participating in the National VA Surgical Risk Study. Main outcome measures . A global rating of quality of care based on chart review. Results . Ratings of overall quality of care did not differ significantly between patients from hospitals with higher and lower than expected mortality and morbidity. On some of the secondary measures, patient care was rated higher for hospitals with lower than expected operative mortality. At the patient level of analysis, those who died or developed complications and had a high predicted risk of mortality or morbidity were rated higher on quality of care than those with a low predicted risk of adverse outcome. Conclusions . The absence of a relationship between most of our measures of process of care and risk‐adjusted outcomes may be due to an insensitivity of chart reviews to hospital‐level differences in quality of care. Site visits to National VA Surgical Risk Study hospitals with high and low risk‐adjusted mortality and morbidity have detected differences on a number of dimensions of quality. The patient‐level findings suggest that the risk‐adjustment models are useful for screening adverse outcome cases for quality of care review.

Intragastric soybean trypsin inhibitor increased plasma CCK bioactivity by 87% in nondeprived, 9–12-day-old rat pups. Reunion with the dam for 1 h after overnight maternal deprivation also increased plasma CCK significantly. These results demonstrate that CCK can be released from the small intestine of rats as early as postnatal day 9.

To investigate the dependence of the satiating action of cholecystokinin (CCK) on serotonergic action at central 5-HT receptors, we examined the effect of systemic pretreatment with 8-OH-DPAT (a 5-HT1A agonist that decreases central 5-HT synthesis and release via an action at somatodendritic autoreceptors in the brainstem raphe) on the suppression of food intake induced by systemic administration of cholecystokinin octapeptide (CKK-8). 8-OH-DPAT significantly attenuated the satiating action of CKK-8. This result is consistent with the hypothesis that peripherally acting CCK recruits central serotonergic processes to elicit normal satiety.

In the past 20 years, the mechanisms of the satiating effect of food that terminate a meal have been inves- tigated intensively in rodents and in humans. This research has revealed that three peptides, cholecystokinin, pancreatic gluca- gon, and bombesin, released by ingested food from the gastroin- testinal tract decrease meal size in a specific, dose-related manner without signs ofacute toxicity or tolerance. In humans, the three peptides decrease meal size without decreasing the reported pleasure or satisfaction of the meal. Although their chemical structure and specific effect justify calling these peptides a new class of anorectic agents, not enough work has been done to evaluate their efficacy for weight loss in obese humans or their safety when administered for months. Am J Clin Nuir 1 992;55:283S-5S.

To examine, in the Veterans Health Administration (VHA), the relation between surgical volume and outcome in eight commonly performed operations of intermediate complexity.In multihospital health care systems such as VHA, consideration is often given to closing low-volume surgical services, with the assumption that better surgical outcomes are achieved in hospitals with larger surgical volumes. Literature data to support this assumption in intermediate-complexity operations are either limited or controversial.The VHA National Surgical Quality Improvement Program data on nonruptured abdominal aortic aneurysmectomy, vascular infrainguinal reconstruction, carotid endarterectomy (CEA), lung lobectomy/pneumonectomy, open and laparoscopic cholecystectomy, partial colectomy, and total hip arthroplasty were used. Pearson correlation, analysis of variance, mixed effects hierarchical logistic regression, and automatic interaction detection analysis were used to assess the association of annual procedure/specialty volume with risk-adjusted 30-day death (and stroke in CEA).Eight major surgical procedures (68,631 operations) were analyzed. No statistically significant associations between procedure or specialty volume and 30-day mortality rate (or 30-day stroke rate in CEA) were found.In VHA hospitals, the procedure and surgical specialty volume in eight prevalent operations of intermediate complexity are not associated with risk-adjusted 30-day mortality rate from these operations, or with the risk-adjusted 30-day stroke rate from CEA. Volume of surgery in these operations should not be used as a surrogate for quality of surgical care.

This report describes the evaluation of the application of bioventing technology to non-petroleum hydrocarbon impacted soils. Bioventing has been thoroughly demonstrated to be a cost-effective remediation technology for a variety of petroleum hydrocarbons. This work included a laboratory column study and a field pilot-scale demonstration to evaluate the potential for applying bioventing to treat dichlorobenzenes in order to expand the list of contaminants impacting Air Force and other Department of Defense Installations beyond petroleum hydrocarbons. A pilot-scale bioventing system consisting of a single vent well and eight tri-level in situ soil gas monitoring points was installed at Hill Air Force Base, Utah. The system was designed to provide oxygen to an anoxic volume of soil and for monitoring the aeration effectiveness and conducting in situ respiration rates. Soil samples were collected at system installation and alter approximately one year of system operation. Significant reductions in dichlorobenzene concentrations were observed over the one year demonstration, only a small portion of which could be accounted for by volatilization. In situ respiration tests indicated that significant biodegradation and supported the results observed in the field. The demonstration was supported by personnel in the Hill Air Force Base Environmental Management Office.