Effects of exercise and environmental complexity on deficits in trace and contextual fear conditioning produced by neonatal alcohol exposure in rats.

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.

Dazoxiben in human sepsis and adult respiratory distress syndrome.

Levels of thromboxane B2 (TxB2), the stable metabolite of thromboxane A2, are elevated in human and experimental septic shock. The thromboxane synthetase inhibitor dazoxiben has improved survival and decreased pulmonary hypertension in experimental endotoxemia. A randomized prospective study of 10 patients with the clinical diagnosis of sepsis and early adult respiratory distress syndrome (hypoxemia, radiologic evidence of the syndrome, and intrapulmonary shunt greater than 20%) was performed to test the efficacy of dazoxiben in ameliorating the effects of human sepsis. Five subjects received dazoxiben and five received placebo. Dazoxiben, 100 mg, or placebo was injected intravenously every 4 hours for a maximum of 72 hours. Plasma immunoreactive TxB2 (iTxB2) levels were determined by radioimmunoassay. Before dazoxiben, the plasma iTxB2 level was 752 +/- 261 pg/ml (n = 5) and was reduced within 1 hour to 333 +/- 137 pg/ml. The plasma levels of iTxB2 remained significantly decreased with subsequent doses of dazoxiben and it was 201 +/- 67 pg/ml (n = 4) 60 hours after dosing. In contrast, placebo had no significant effect on plasma iTxB2 levels (n = 5) throughout the entire period of observation. Dazoxiben did not induce any significant changes in pulmonary or systemic vascular resistance, intrapulmonary shunting, clotting studies, or extravascular lung water. One of the five subjects in the placebo group died and two of the five subjects in the dazoxiben group died. We conclude that dazoxiben was safe and effectively lowered plasma iTxB2 levels in patients with sepsis and incipient adult respiratory distress symptom, but did not significantly alter the hemodynamic and pulmonary sequelae of established sepsis.

Autonomic and behavioral correlates of appetitive conditioning in rats.

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.

Delayed development of fear-potentiated startle in rats.

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.

An ontogenetic comparison of ethanol-mediated taste aversion learning and ethanol-induced hypothermia in preweanling rats.

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).

Increases in ethanol ingestion by young rats following interaction with intoxicated siblings: a review.

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.

Speaking the language of finance.

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.

Bleeding ulcer: timing and technique in surgical management.

The individual surgeon's training, experience and flexibility are decisive factors in the successful recovery of patients after surgery for acute bleeding peptic ulcer. With planned management, careful preparation for surgery should be considered as of equal importance to surgical skill. Early diagnosis and exact resuscitation are the two most important aspects of a plan of treatment which anticipates the need for early surgery. In the past, patients were often referred late for surgery after significant blood loss and transfusion. Surgeons have endeavoured to define the cases that are likely to rebleed and prepare them promptly for surgery. Probably the best indications for early surgery are severe haemorrhage, reflected by shock on admission, an age of over 50 and active bleeding from the ulcer seen at diagnostic endoscopy. Prospective studies have shown a reduction in mortality from bleeding ulcer where policy requires early endoscopic diagnosis, exact resuscitation in the intensive care unit and early surgery in high risk cases.

A further investigation of the developmental emergence of fear-potentiated startle in rats.

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.

Surgical management of bleeding chronic peptic ulcer. A 10-year prospective study.

Analysis of experience with chronic bleeding peptic ulcer in 504 patients, admitted from 1960 to 1971, shows a hospital mortality of 12%. This retrospective review suggested that early endoscopic diagnosis, adequate resuscitation and a policy of early selective surgery was necessary if mortality was to be reduced. With this policy, there were 37 deaths in 633 patients admitted during the period of prospective study from 1972 to 1982 (5.8%). There were 25 deaths after emergency surgery in 206 patients, 56% of postoperative deaths were related to technical factors and 44% to nontechnical complications. Comparison with the retrospective study from 1961 to 1970 showed, matching in terms of incidence of shock, sex distribution and number of patients over 60 years of age. During this period, 142 emergency operations were performed, with 25 postoperative deaths, an operative mortality of 17.6%. Thirty-five deaths occurred in conservatively treated patients (9.5%) compared with 12 deaths in conservatively treated patients from 1972 to 1982 (2.6%). Within the period of prospective study, there was a significant reduction in mortality from 8%, for the first 5 years, to 3.9% for the second 5 years of study. These two periods matched except for a significant increase in the proportion of patients 60 years and over. This was mainly due to a rise in incidence of aged patients with gastric ulcer. Also noted was a decrease in mortality in patients 60 years and over which reached significance, and a significant decrease in the number of deaths in shocked patients. A significant fall in technically related postoperative complications was noted, from 44 (11 causing death) to 12 (three causing death) during the second 5 years of prospective study. There were 444 patients admitted with bleeding duodenal ulcer with 20 deaths in hospital (4.5%), and 17 deaths in 189 patients admitted with bleeding gastric ulcer, a mortality of 9%. No single factor could be isolated as the reason for the improved results. Possibly the most significant reason is the application of a defined policy in a special unit where staff became familiar with all aspects of the problem of bleeding chronic peptic ulceration.

Management of acute bleeding gastric malignancy.

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.

Perforation in patients with bleeding ulcer.

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.

The detection of serological factors in acute ulcerative colitis indicating a favourable short-term prognosis.

Large-intestinal epithelial cells were obtained from operation specimens and by biopsy at sigmoidoscopy from 16 patients with acute severe mucosal ulcerative colitis and II control subjects with normal large-bowel mucosa. The ability of lymphocytes to release 51Cr label from large-intestinal epithelial cells was quantitatively assessed as percentage lymphocyte activity. The mean +/- standard deviation of percentage lymphocyte activity in 16 patients with acute ulcerative colitis on admission to hospital (88 +/- 8) was significantly greater than that in II normal subjects (16 +/- 8) (P is less than 0.01). In each study, samples of autologous serum were added to two reactions between lymphocytes and autologous large-intestinal epithelial cells. The results in the seven patients who came to urgent colectomy differed significantly from those in the nine who responded to corticosteroids. The mean +/- S.D. of percentage serological inhibition of lymphocyte activity in the group coming to colectomy was 44 +/- 16, and in those responding to steroids 12 +/- 5. When the serum of these patients was studied for immunofluorescent autoantibodies to normal human colonic mucosa, none of the seven patients treated by colectomy had detectable autoantibodies, in contrast with three of the nine patients with a more favourable short-term prognosis, in that they responded to steroid treatment.

The in-vitro action of lymphocytes on autologous colon epithelial cells in ulcerative colitis.

The action in culture of peripheral blood lymphocytes on autologous large-intestinal epithelial cells was studied in 13 patients with severe mucosal ulcerative colitis. Two different methods were used to measure lymphocyte activity. These showed that autologous-lymphocyte-induced release of isotopic label and detachment in monolayer culture of large-intestinal epithelial cells was increased in acute ulcerative colitis when compared with findings in the same studies in six normal subjects. Subsequently in four of the six patients who responded to cortisone it was shown that lymphocyte activity against epithelial cells returned to the normal range. Further control studies showed little lymphocyte activity against autologous skin and ileum, suggesting that autologous-lymphocyte-induced damage of large-intestinal epithelial cells is a tissue-specific reaction in patients with acute ulcerative colitis. The absence of reactivity in other colonic inflammatory diseases also suggested that such increased in vitro lymphocyte activity is disease-specific for ulcerative colitis.

Perforation in Crohn's disease of the small bowel.

During a five-year period, three patients with general peritonitis, secondary to perforation of the small bowel in Crohn's disease, were successfully treated by resection and primary anastomosis. During this period, 30 patients presented with small bowel or ileocaecal Crohn's disease. The possibility of perforation should be considered when evaluating the need for surgery in patients with Crohn's disease with symptoms of obstruction.

Lymphoblastic response to autologous colon epithelial cells in ulcerative colitis in vitro.

The blastic transformation in vitro of peripheral blood lymphocytes was measured by the 72-hour uptake of tritiated thymidine ((3)H-6-thymidine) in 23 patients with mucosal ulcerative colitis, three patients with acute Crohn's colitis with rectal involvement, and seven normal subjects. The 23 patients with ulcerative colitis were subdivided into three groups, graded according to severity into seven with acute, severe, nine with active, chronic, and seven with quiescent disease. In the control cultures of lymphocytes without any added potential stimulant the uptake of (3)H-6-thymidine in the clinical subgroup of seven patients with acute, severe ulcerative colitis was significantly greater than in seven normal subjects (p<0.01). This contrasted with a reduced uptake of (3)H-6-thymidine by lymphocytes from seven patients with acute severe colitis when compared with seven normal subjects after stimulation with phytohaemagglutinin-P (PHA-P) (p<0.01). In further duplicate cultures of lymphocytes specifically stimulated by an equal number of viable autologous rectal epithelial cells, the uptake of (3)H-6-thymidine was significantly greater in seven patients with acute severe colitis when compared with seven normal subjects (p<0.01). The results in three patients with acute Crohn's colitis with rectal involvement showed no such evidence of lymphocyte sensitivity to autologous rectal epithelial cells and their uptake of (3)H-6-thymidine lay within the normal range.Evidence that the degree of lymphoblastic transformation was related to the clinical severity of ulcerative colitis was provided by the results obtained in the unstimulated and epithelial cell stimulant cultures. The uptake of (3)H-6-thymidine was directly related to the clinical severity of ulcerative colitis in the three subgroups studied. In addition, four of the seven patients with acute severe colitis were studied later in clinical remission. They were then found to have a significantly reduced uptake of (3)H-6-thymidine in response to autologous rectal epithelial cells (p < 0.01).