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Biomedical subjects

P S Hunt

Publications and source records attributed to P S Hunt.

At least 19 recordsLinked to original sources

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).

Aging

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.

Contraindications

Choice of emergency operative procedure for bleeding duodenal ulcer.

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.

Adolescent

Ethanol-mediated taste aversions and state-dependency in preweanling (16-day-old) rats.

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.

Animals

Age-dependent facilitation of taste-footshock conditioning by prior exposure to the training context.

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.

Aging

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.

Aged

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.

Adult

A ten year prospective experience with semi-elective shunt in selected patients for bleeding oesophageal varices.

In a prospective study from 1972 to 1982, 38 patients with bleeding oesophageal varices and relatively good liver function were treated by semi-elective or emergent shunt 2-4 weeks after admission. There were no deaths within 3 months of surgery. This constituted 30% of the total 125 patients admitted with bleeding varices during that period. No referred case for treatment of portal hypertension was included in this study. The procedures performed were end-to-side portacaval shunt in 30 cases, lieno renal shunt in seven cases and interposition mesenterico-caval shunt in one case. All patients were admitted to a special unit with a two stage policy of management. Immediate endoscopic diagnosis and balloon tamponade in those with continued bleeding was followed by shunt in selected cases. Follow-up of the 38 patients showed a cumulative survival at 1 year of 89%, at 3 years of 75% and 5 years of 65%. In four cases (13%) a clinical diagnosis of portal systemic encephalopathy was made, all were controlled by medical management. In four of ten follow-up deaths, liver failure was the cause, in none of these cases was encephalopathy a problem. It is concluded that with a policy of early diagnosis and control of haemorrhage, 30% of a typical series of prospectively studied patients admitted with bleeding varices can be treated without mortality by definitive surgery. There was low incidence of encephalopathy and no cases of incapacitating mental confusion. Centralization of treatment and prospective study is essential for the implementation of such a policy of management.

Adult

Haemorrhage from smooth muscle tumours of the upper gastro-intestinal tract.

Eight patients with haemorrhage from smooth muscle tumours of the upper gastro-intestinal tract were treated during a 10 year period from 1973 to 1982. Seven of the tumours were benign and one a malignant leiomyoblastoma. Seven tumours were sited in the stomach and there was one duodenal lesion. Endoscopy was performed in all eight cases and made the diagnosis definitively in four. In two cases the diagnosis was confirmed on barium meal and in the other two, diagnosis was eventually made at laparotomy. Two patients were shocked on admission and required emergency surgery. In one case a diameter greater than 10 cm suggested malignant potential and wide local resection was performed. In one other case with a tumour in the antrum, a distal partial gastrectomy was performed, and in the case with leiomyoblastoma a proximal gastrectomy was performed. One case was lost to follow-up. The mean follow-up in six cases free of disease with benign tumour was 2.6 years. The patient with a tumour of greater than 10 cm in diameter remains well at 18 months follow-up and the patient with a malignant leiomyoblastoma died 2 years after surgery.

Aged

Mortality in patients with haematemesis and melaena: a prospective study.

In a prospective study of death in 817 patients with haematemesis and melaena admitted on 894 occasions, the protocol included admission of all patients to a defined unit, early endoscopy and resuscitation, and planned management. Over the three consecutive two-year periods of the study mortality significantly decreased from 9% to 2.4%. Although the operative rate remained the same, the operative mortality fell from 16% to 1.6%. The fall in mortality was greatest in patients with bleeding gastric ulcers. These results suggest that prospective studies with a defined policy can influence the mortality in patients with upper gastrointestinal bleeding.

Adolescent

Tinidazole in the prevention of wound infection after elective colorectal surgery.

During the first six months of 1978, 71 patients were the subject of a controlled trial of the use of tinidazole for the prevention of wound infection after elective colonic surgery. The trial design was prospective, randomized and double-blind with tinidazole or placebo given at the last oral intake before operation. The objective endpoint of the trial was the presence or absence of wound infection manifested by pus. All patients underwent a standard preoperative preparation of bowel washouts, and a standardized surgical technique included, in all cases, the use of wound drainage. At the end of the trial there were three wound infections in 40 patients who were given tinidazole, and eleven wound infections in 31 patients who were given placebo. The difference in wound infection rate between these two groups is significant (x2 with Yates correction = 7.3; P less than 0.01).

Clinical Trials as Topic

Bleeding duodenal ulcer: reduction in mortality with a planned approach.

In a 6-year prospective study from 1972 to 1978 266 patients were admitted to a haematemesis and melaena unit with bleeding duodenal ulcer. There were 13 deaths, a mortality of 5 per cent. A comparison between the three consecutive 2-year periods of study showed an initial mortality of 6 per cent for the first 4 years falling to 2 per cent for the 93 admissions during the final 2 years of experience. Of the 120 patients treated surgically, 10 died in hospital, giving an operative mortality of 8 per cent. The trend in operative mortality was from 13 per cent for the initial 2-year period to 8 per cent for the second period and to 3 per cent for the final 2 years. The operative rate was consecutively 45, 50 and 34 per cent. There was 1 death in conservatively treated patients during each 2-year period of study. Three types of operation were performed: vagotomy, pyloroplasty and oversewing of the ulcer; Polya gastrectomy; and vagotomy and antrectomy. There was no difference in morbidity and mortality between these operations. At a mean follow-up of 3.1 years, 90 per cent of the patients had a good result from their operation. It is concluded that a prospective system of management with an active policy of early endoscopy, surgery and regular audit reduces the mortality from bleeding duodenal ulcer.

Adult

The Mallory-Weiss lesion as a cause of upper gastrointestinal bleeding.

A prospective study of patients with upper gastrointestinal bleeding admitted to a haematemesis and melaena unit has revealed an incidence of Mallory-Weiss tears of 8% (59 of 762 patients undergoing endoscopy). Prior vomiting was present in 60% and an associated upper gastrointestinal lesion in 44 percent. The majority of patients had a recent ingestion of alcohol and/or analgesics, whilst 34% had chronic heavy alcohol intake. Approximately 50% of patients required no blood transfusion, while 37% had over three units of blood. No patient in the group required surgical intervention, and one patient died because of general debility. This study suggests that the Mallory-Weiss tear accounts for a significant proportion of patients admitted with upper gastrointestinal bleeding, but that the mortality and morbidity are low.

Adolescent

Bleeding stomal ulceration.

In a prospective study of patients with haematemesis and melaena, there were 22 admissions of patients with bleeding stomal ulceration, representing 2.5% of total admissions to the Unit. In 16 patients the bleeding was from superficial stomal lesions. These lesions, endoscopically and histologically, resembled alkaline reflux gastritis, a recently defined cause of postgastrectomy bile vomiting. Five patients presented with chronic ulceration following inadequate gastric surgery. One patient was admitted on two occasions. Nine patients received more than five units of blood and came to operation for continued bleeding. In seven of the surgical cases, the bleeding was from superficial stomal lesions. Our experience suggests that truncal vagotomy is necessary to control the bleeding in these patients. One patient presented with superficial stomal ulceration and carcinomatous change. This patient died. It is important to subject these lesions to biopsy, and biopsy with extension of a previous gastrectomy is indicated to control bleeding, and to exclude malignancy.

Adult

Mortality trends in the surgical management of chronic peptic ulceration: 25 years' experience.

This study is of the results of surgical management of bleeding chronic peptic ulceration at Prince Henry's Hospital, retrospective for the periods 1951 to 1960 and 1961 to 1970 and prospective for 1972 to 1977. During the latter five years all patients were admitted from the community to a haematemesis and melaena unit with a defined policy of management and prospective data recording for computer analysis. There was a continuing improvement in mortality over this 25-year period, especially with duodenal ulcer. No clear distinction could be made between conservative surgery and partial gastrectomy in terms of reduced surgical mortality in duodenal ulcer. Bleeding gastric ulcer remains a difficult problem, with a current surgical mortality of 21%.

Adolescent