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In rodents, voluntary exercise and environmental complexity increases hippocampal neurogenesis and reverses spatial learning and long-term potentiation deficits in animals prenatally exposed to alcohol. The present experiment extended these findings to neonatal alcohol exposure and to delay, trace, and contextual fear conditioning. Rats were administered either 5.25 g/kg/day alcohol via gastric intubation or received sham-intubations (SI) between Postnatal Day (PD) 4 and 9 followed by either free access to a running wheel on PD 30-41 and housing in a complex environment on PD 42-72 (wheel-running plus environmental complexity; WREC) or conventional social housing (SHSH) from PD 30 to 72. Adult rats (PD 80 ± 5) received 5 trials/day of a 10-s flashing-light conditioned stimulus (CS) paired with .8 mA footshock either immediately (delay conditioning) or after a 10-s trace interval (trace conditioning) for 2 days. Neonatal alcohol exposure impaired context and trace conditioning, but not short-delay conditioning. The WREC intervention did not reverse these deficits, despite increasing context-related freezing in ethanol-exposed and SI animals.

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Nursing leadership skills have changed dramatically in a short period of time. Just being able to cover the schedule and ensure adequate orientation for new employees are not enough in today's health care environment. This article outlines steps to ensure adequate staffing levels, assess productivity, and justify the operational supplies and capital equipment necessary for effective patient care. It also outlines steps nursing leaders can take to market their programs and services.

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A novel procedure for enhancing voluntary intake of ethanol in periadolescent rats is described. The procedure is a modification of Galef et al.'s (e.g., Galef, Kennett, & Stein, 1985; Anim Learn Behave 13:25-30) demonstrator-observer procedure. Subjects were Sprague-Dawley rats, 28-35 days of age. The experimental subject (observer) interacted with a same-sex conspecific (demonstrator) previously administered (a) 1.5 g/kg ethanol, (b) an equal volume of water, or (c) 2.1% Sanka coffee intragastrically. Observers were tested with 24-hour access to ethanol and coffee solutions. Observers that had interacted with demonstrators administered ethanol ingested significantly more ethanol during the test than observers in the other two groups. In Experiment 2 demonstrators were administered one of several doses of ethanol (0.0, 1.0, 1.5, or 3.0 g/kg) and observers' ethanol intakes were assessed. Only those observers that interacted with 1.5 g/kg demonstrators increased their ingestion of ethanol, relative to water controls. The lower (1.0 g/kg) and higher (3.0 g/kg) dose groups did not show altered ethanol ingestion. These results are discussed with respect to threshold levels of respired ethanol cues and the ability of observers to detect these cues from demonstrators. The demonstrator-observer procedure appears to be effective for the social transmission of preferences for ethanol in periadolescent rats.

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Although there are a variety of animal models used in alcoholism research, there has been very little experimental investigation into possible environmental/experiential factors leading to an initial bout of alcohol ingestion. Adolescent alcohol abuse is a major problem in today's society and research is beginning to focus on the predisposing conditions toward alcohol consumption, particularly in this vulnerable age group. The results of recent research from our laboratory are reviewed in which voluntary ingestion of ethanol by preweanling and adolescent rats is increased following exposure to an intoxicated sibling. This paradigm centers on the notion that rodents, and perhaps other mammalian species as well, acquire information about foods to ingest based in part on interaction with a conspecific that has recently ingested a novel diet (e.g. Galef, 1981). Smelling food-derived cues on the breath of another animal is known to affect later food choice. The procedures described in this paper represent a potential new model for examining the effects of early exposure to ethanol through social interactions on the initiation of voluntary alcohol ingestion.

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Recently Hunt, Holloway, & Scordalakes (1999) described a novel procedure for examining how social interactions with an intoxicated sibling can enhance periadolescent rats' voluntary intake of ethanol. In the present series of experiments we extend these findings to preweanlings. In Experiment 1, same-sex sibling 16-day-olds were assigned to be either (a) a demonstrator that was administered 1.5 g/kg ethanol or water control or (b) an observer that was tested for ethanol intake following a brief interaction with the demonstrator. Observers interacting with EtOH demonstrators exhibited increased intake of ethanol relative to observers interacting with water demonstrators. In Experiment 2, subjects were 8, 12, or 16 days of age and at all ages, ethanol intakes increased following exposure to an intoxicated sibling. In Experiment 3, repeated exposures to ethanol demonstrators on days 12, 14, and 16 was found to promote ethanol intake after weaning (on postnatal day 22). Collectively these data indicate that exposure to ethanol cues in the context of home/social cues can lead to modifications in ethanol acceptance, and that repeated exposures to such cues during infancy can impact ethanol ingestion after weaning.

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This series of experiments was designed to reexamine the ontogenetic emergence of the fear-potentiated startle response in rats. Previous results (Hunt, Richardson, & Campbell, 1994) indicated that potentiated startle to a light conditioned stimulus (CS) paired with an acoustic unconditioned stimulus (US) was not observed until 30 days of age. In the present experiments, subjects were given pairings of a light CS with a brief footshock unconditioned stimulus (US) and were tested for fear-potentiated startle 24 hr later. Subjects 23 and 30 days of age exhibited significant potentiated responding in the presence of the light, while 17-and 20-day-olds did not. Subjects 17 days of age did reliably express conditioned decreases in heart rate to the light at the 24-hr test. The failure to observe fear-potentiated startle at the youngest age was shown not to be due to a general disruption of conditioned fear responding by either (a) pretest startle stimulus presentations or (b) contextual characteristics of the startle testing apparatus. The capacity to express fear through a potentiated startle response develops later than the capacity for other defensive responses in the rat.

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It is generally recognized that during development the capacity to express learning in terms of changes in somatomotor activity is evident earlier than the capacity for learned changes in autonomic responding (e.g., heart rate). In this series of experiments, findings indicate that changes in heart rate to a visual conditioned stimulus (CS) paired with a footshock unconditioned stimulus (US) can be observed as early in development in the rat as freezing responses. However, cardiac responses are inhibited from being expressed by preweanlings (but not adults) during CS-US pairings, the time when heart rate responses are often measured. This inhibition appears to arise from US exposure, and dissipates completely within 2 hr of training. These findings are discussed with respect to developmental changes in US-evoked autonomic arousal and response system dissociations.

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The cardiac responses accompanying conditioned stimulus- (CS)-generated (orienting) and unconditioned stimulus- (US)-generated appetitively motivated behaviors (P. C. Holland, 1977) were investigated. On the basis of contemporary psychophysiological research, CS-generated responses were predicted to produce bradycardia, and US-generated responses to produce tachycardia. Pairing a 10-s visual CS with food delivery produced conditioned behavioral orienting (rearing) during the initial portion of the CS, followed by magazine approach (US-generated) responses as the CS progressed. CS onset produced a decrease in heart rate, mediated by an increase in parasympathetic stimulation of the heart, which persisted throughout the 10-s CS; no support for a biphasic cardiac response was observed. These data are discussed with respect to other conditioned autonomic responses and their relevance to foraging and food ingestion.

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Pairing an olfactory conditioned stimulus (CS) with an acoustic startle unconditioned stimulus (UCS) produced conditioned bradycardia in rats ranging from 12 days of age to adulthood but failed to produce conditioning in 10-day-olds (Experiment 1). The second experiment compared the effects of two different UCSs, acoustic startle and electric shock. The startle UCS produced conditioned bradycardia accompanied by immobility. In contrast, the shock UCS produced conditioned tachycardia accompanied by behavioral activation. Pharmacological analysis revealed that activation of the parasympathetic nervous system (PNS) produced the conditioned bradycardia (Experiment 3) and that activation of the sympathetic nervous system (SNS) produced the conditioned tachycardia (Hunt, Hess, & Campbell, 1994). Further comparisons revealed that the startle UCS established conditioning several days earlier in development than the shock UCS. The ability of the PNS to respond to phasic stimulation earlier in development than the SNS was discussed as a possible mechanism for the early development of conditioned bradycardia.

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BACKGROUND: A consecutive series of 269 cases of bleeding gastric ulcer were studied prospectively from 1979 to 1993 inclusive. METHOD: Fifty-five (21%) had a giant gastric ulcer with a diameter of 3 cm or more. These cases were compared with those with ulcers less than 3 cm in diameter in terms of clinical details, prognostic factors, urgent operation and outcome. RESULTS: Death occurred in 13 cases (5%), urgent surgery was performed in 75 cases (29%) and there were 11 postoperative deaths (15%) within a month of surgery. The patient details in the two groups matched in terms of age, sex distribution, ulcer history, previous complication and recent ingestion of analgesics. Clinical comparison showed that giant ulcer had a poorer prognosis with a higher mortality (10 vs 3%, P < 0.01), urgent surgery rate (65 vs 12%, P < 0.01) and operative mortality (23 vs 11%, difference not significant). Study of risk factors in patients with giant ulcer revealed significantly more with concurrent illness, shock, anaemia and endoscopic stigmata of recent haemorrhage. CONCLUSION: More severe bleeding and poorer general condition in the giant ulcer group stresses the importance of early diagnosis and accurate resuscitation in these patients. Survival depends on optimal condition and prompt and timely surgery.

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The developmental emergence of fear-potentiated startle was examined in rats ranging in age from 16 to 75 days. In Experiment 1, a pure tone served as the conditioned stimulus (CS) and an acoustic startle pulse served as the unconditioned stimulus (US) for fear conditioning. Fear-potentiated startle by the tone CS was observed in rats 23 days of age and older but not in rats 16 days of age. In Experiment 2, a light served as the CS. Rats 30 days of age and older showed fear-potentiated startle, whereas 23-day-old rats did not. The final experiment demonstrated that another behavioral index of fear, stimulus-elicited freezing, was observed earlier in development than fear-potentiated startle, confirming the effectiveness of the training procedure for conditioning fear. The results suggest that fear-potentiated startle is a relatively late-emerging response system, paralleling the development of conditioned autonomic changes (e.g., heart rate) rather than that of freezing.

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Gastric malignancy was the cause of bleeding in 35 of a consecutive series of 2260 cases (1.5%) treated with upper gastrointestinal haemorrhage. Fifteen patients came to emergency surgery (43%). In 13 of 30 early endoscopies performed the lesion was thought to be benign (43%) and seven of these cases came to emergency surgery. Two patients died after 15 emergency operations (13%) compared with 15 deaths after 109 emergency operations (14%) for benign gastric ulcer during the same period of study. A total of four patients with malignant ulceration died after surgery in 33 cases (12%), two after 15 emergency operations and two after 18 elective procedures. The only significant predictors of urgent surgery for malignant ulcer were shock on admission and active bleeding or visible vessel on endoscopy. Resection of gastric malignancy was performed in 29 patients during initial admission and in four cases at a subsequent admission giving a final resection rate of 91%. Of the 28 patients with adenocarcinoma, 19 had localized disease (Stage I or II) (68%). Nine patients were treated by total gastrectomy, five at an initial elective procedure and four at a second procedure.

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Several studies have confirmed that diet selection patterns of adult rats are at least partially established as a result of early experiences with food-related stimuli present in the milk of a lactating female (e.g., Capretta & Rawls, 1974; Galef & Clark, 1972; Galef & Henderson 1972). The present experiments were designed to investigate whether preweanling rats would similarly modify their acceptance of an ethanol solution following exposure to this cue in a nursing context. In Experiment 1, 8-, 12-, and 16-day-old rats were given ethanol, delivered intraorally in compound with milk, while given the opportunity to suckle an anesthetized dam. Subsequent testing revealed that 12- and 16-day-old subjects evidenced enhanced intake of the ethanol relative to controls, while 8-day-olds did not. Finally, the oldest (16 days of age) subjects also expressed a conditioned aversion to the milk when tested 24 hr after conditioning and ethanol-ingestion testing. Experiment 2 demonstrated that the critical factor for ethanol conditioning was the opportunity to suckle, rather than the simultaneous presence of milk. Finally, the aversion to milk observed in Experiment 1 was shown to have resulted from long-delay learning, due to the ingestion of a sufficient dose of ethanol during testing to serve as an aversive unconditioned stimulus (Exp. 3).

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Three experiments were designed to evaluate the acquisition and expression of tolerance to ethanol in preweanling rats. Administrations were begun on Postnatal Day 13 (PD13) and continued, on alternating days, through PD23. Following either three or five administrations of a 2.5 g/kg dose of ethanol, animals expressed tolerance to the motor-impairing consequences of acute ethanol, as measured through attenuated latencies to perform a righting reflex. However, no tolerance was evident when it was assessed through the hypothermic response to ethanol delivery (Experiment 1). The results of subsequent experiments suggested that this tolerance was not due to lower levels of ethanol in the blood and brain of the chronically exposed subjects (Experiment 2) nor to the development of behavioral tolerance, such as learning to perform the motor task in the presence of intoxication (Experiment 3). Additional tests determined that tolerance level did not alter the infant rats' ability to learn about the orosensory cues associated with ethanol delivery. Specifically, tests confirmed previous studies that an aversion to ethanol odor was formed as a result of the chronic administration procedure, presumably due to the animals associating the orosensory properties of eliminated ethanol during intoxication with the aversive consequences of this state. These results provide evidence that tolerance can develop in the preweanling rat, and that at least one measure (righting reflex) can be used to assess its development early in life.

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To examine the interactive effects of ethanol (EtOH) and ambient temperature, 10-, 16-, and 20-day-old rat pups ingested pairings of sucrose solution and various doses of ethanol (intubated intragastrically) and were then exposed to relatively low or relatively high ambient temperatures. Ten- and 20-day-old pups required a higher EtOH dose than did 16-day old pups for conditioning of a sucrose aversion and for hypothermia. These age-related differences might be due to ontogenetic changes in the production and accumulation of acetaldehyde, a metabolite of EtOH. For all ages, EtOH-induced hypothermia was necessary for conditioning of the taste aversion, which is in accord with results of previous tests with adult rats (Cunningham, Hawks, & Niehus, 1988).

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Twelve patients developed perforation after haemorrhage in a consecutive series of 840 cases admitted for bleeding chronic peptic ulcer. Death occurred in 3 of the 9 cases with duodenal ulcer and 1 of the 3 cases with gastric ulcer. There were 5 giant and 4 kissing duodenal ulcers and all 3 cases with gastric ulcer had a giant ulcer. The 12 patients were similar to the rest of the series in terms of ulcer site and shock on admission but were older and in poorer medical condition, more had ingested analgesics, more had giant ulcers and the mortality was greater (33% vs 6%). Giant ulceration was the only risk factor of potential clinical value as a predictor of the danger of ulcer perforation. One death occurred in 8 cases treated by early definitive surgery, suggesting this to be the treatment of choice for this unusual complication of peptic ulcer.

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Requirements for conditioning of an ethanol-mediated taste aversion in 16-day-old rat pups were examined. Experiment 1 demonstrated that preweanling rats are capable of acquiring, in two trials, an aversion to a 15% sucrose solution when followed by intragastric intubation of a 1.2 g/kg dose of 17% v/v ethanol, but not when followed by a 0.4 g/kg dose. Comparison was with control animals given sucrose followed by an equivalent volume isocaloric Half and Half. When the 0.4 g/kg dose of ethanol preceded sucrose presentation by 30 min (Experiment 2), the aversion was learned, suggesting that the effective delay between the sucrose and the critical consequences of the ethanol had been too long with the former procedure. Expression of the sucrose aversion required, however, the reinstatement of the context of intoxication--state-dependent retention. Finally, the results of Experiment 3B indicated that, in addition to the association between the sucrose and the aversive consequences of alcohol intoxication, the orosensory cues resulting from alcohol's direct elimination, via such processes as respiration and salivation, became associated with the appetitive properties of the sucrose. This was evidenced by a conditioned increase in preference for ethanol odor. Possible age-related differences in the ability to associate stimuli with alcohol's unconditioned consequences, and in state dependency are discussed.

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In a consecutive series of 201 emergency operations in patients with bleeding duodenal ulcer the size of the ulcer was the only factor that showed a significant correlation with the procedure chosen. Vagotomy, pyloroplasty and underrunning of the bleeding point was performed in 101 cases with ten deaths (10 per cent), partial (Billroth II) gastrectomy in 81 cases with ten deaths (12 per cent), and vagotomy and antrectomy in 16 cases with one death (6 per cent). A patient was more likely to be treated by partial gastrectomy if a giant ulcer with an internal diameter of greater than or equal to 2 cm was found. The results suggest that while vagotomy and pyloroplasty, combined with a direct attack on the bleeding point or excision of an anterior ulcer is an acceptable standard emergency operation for bleeding duodenal ulcer, gastric resection proved to be a satisfactory alternative procedure and should be considered in the technically difficult case with a very large ulcer. A giant ulcer was present in 37 per cent of cases coming to surgery.

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Among adult rats, gustatory stimuli are easily associated with illness, but not with external unconditioned stimuli such as footshock. Recent evidence indicates, however, that this cue-to-consequence specificity may vary ontongenetically. The present studies examined the acquisition of an aversion to a taste paired with footshock in 5- and 15-day-old rats. Consistent with previous reports, 5-day-old rats avoided the taste that preceded footshock, while 15-day-old subjects did not express an aversion to the taste paired with footshock. Exposure to the training context for either 1 or 5 h prior to conditioning disrupted taste-footshock conditioning in the 5-day-old subjects. For the 15-day-old subjects, 1 h of pre-conditioning exposure to the training context had no effect on conditioning, whereas a longer duration of preexposure promoted conditioning to the taste cue. The results suggest ontogenetic differences in stimulus selection.

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