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The clinical, radiological and hepatic histological features of 51 patients with hepatobiliary fibropolycystic disease were reviewed. Many of the patients had more than one of the diseases; the combination of both congenital hepatic fibrosis (CHF) and Caroli's disease was most striking. Twelve patients with CHF (50% male) presented at 6 +/- 2 years of age (mean +/- SEM) with hepatosplenomegaly or variceal bleeding. Their main problems were recurrent variceal bleeds and renal disease. Polycystic kidneys and renal stones were present in 79% and chronic renal failure in 30%. Six of the 8 patients with Caroli's disease were male (75%) and presented later (aged 37 +/- 8 years) with hepatomegaly or cholangitis. Recurrent cholangitis developed in most (7/8) and 2 had polycystic kidneys. Twelve patients had a combination of CHF and Caroli's disease presenting with hepatosplenomegaly, bleeding or cholangitis. As in Caroli's disease, most (83%) were male, but the age of presentation (15 +/- 4 years), and the incidence of polycystic kidneys (42%) and renal failure (8%) was intermediate between CHF and Caroli's disease. In these patients, bleeds always predated cholangitis. Histologically, acute cholangitis was superimposed on the changes of CHF. Adult polycystic liver disease (10 patients) presented later (43 +/- 3 years) in females (90%) with pain, a mass or incidentally; polycystic kidneys were present in 33%. Microhamartomas (10 patients), which were usually incidental findings, were diagnosed latest (50 +/- 6 years). Three choledochal cysts were seen. The hazard of cancer in these diseases was reflected by 2 bile duct cancers and 1 pancreatic cancer (incidence 6%). This study has confirmed that hepatobiliary fibropolycystic diseases form part of a family and are often associated together. However, the diseases are of greatly differing severity and the prognosis in an individual patient is determined by the fibropolycystic diseases present.
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PMID:Hepatobiliary fibropolycystic diseases. A clinical and histological review of 51 patients. 395 71

To determine whether electrical stimulation of the periaqueductal gray region decreases anesthetic requirement, the authors studied the effect of such stimulation on the MAC of halothane and 60% nitrous oxide in 33 patients. These patients, who were undergoing implantation of a radio-frequency-coupled receiver and connection of that receiver to electrodes previously implanted in the periaqueductal gray area, were assigned randomly to receive (n = 16) or not receive (n = 17) electrical stimulation 1 h before surgery. The mean value (+/- SEM) for the minimum alveolar concentration of halothane combined with 60% nitrous oxide was significantly less (P less than 0.001) for patients who were stimulated preoperatively (0.15 +/- 0.05%) than for those who were not (0.51 +/- 0.02%). The authors conclude that stimulation of the periaqueductal gray region decreases anesthetic requirements and believe that at least three mechanisms are possible: a nonspecific narcotic-like effect, a specific effect on a pain pathway, or an effect on specific neural pathways that affect anesthetic requirements secondary to changes in regional concentrations of neurotransmitters.
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PMID:Reduced anesthetic requirement after electrical stimulation of periaqueductal gray matter. 397 Mar 61

Erectile impotence is a common and distressing problem in diabetic men. In order to examine the impact of a penile prosthesis on the quality of life of the recipients, we mailed a questionnaire to all patients (N = 49) who received a semi-rigid (Small-Carrion) prosthesis at the Seattle VAMC from 1976 to 1981. Fourteen patients with diabetes and 23 without diabetes returned the questionnaire. Direct comparisons showed no statistically significant differences between the responses of the two groups. Based on a scale of 1-7 (1 = worst, 4 = no change, 7 = best), the general effect of the operation on the quality of life of the recipients was 5.7 +/- 0.3 (Mean +/- SEM); the quality of intercourse was 5.1 +/- 0.3; the patient's perception of his partner's response to the prosthesis was 5.2 +/- 0.3; and the patient's perception of postoperative changes in his relationship with his partner was 5.6 +/- 0.3. Eighty-three percent of the patients were satisfied with the performance of the prosthesis. Most of the patients (86%) felt that their preoperative expectations had been fulfilled and would elect to have the procedure if they had it to do over again. However, five patients (14%) stated that they would not elect the operation again because their partners did not appreciate the operation (N = 2); the operation produced severe, prolonged pain (N = 1); or the patient's expectations had not been fulfilled (N = 2). Preoperative counseling should be used to foster realistic patient and partner expectations. This operation, which appears to improve the quality of life for most diabetic patients with erectile impotence, should be considered a part of standard care and not as a cosmetic procedure or extraordinary care.
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PMID:Attitudes of diabetic men after implantation of a semi-rigid penile prosthesis. 399 73

1. We examined the effect of ischaemic pain and sustained isometric muscle contraction on plasma immunoreactive gamma-lipotropin (gamma LPH), beta-endorphin/beta-lipotropin (beta END/beta LPH) and corticotropin (ACTH), which are all synthesized from a common precursor (pro-opiocortin), and plasma cortisol in 10 normal subjects. 2. Experimental pain was produced by inflation to 250 mmHg of a sphygmomanometer cuff, placed above the elbow of the 'dominant' arm, after which the subject squeezed a hand dynamometer, loaded to 12 kg, 20 times at 2 s intervals. Blood was drawn before, after 5 and 10 min of pain, and 30 min after release of the cuff. In a control session, the subjects were asked to squeeze the handgrip alone for 5 min at 30% of their maximum strength, a procedure which elevates the blood pressure without causing pain. 3. One subject had unexplained high (30--71 pmol/l) baseline peptide concentrations. Baseline values for the nine other subjects were: ACTH, 7.3 +/- 1.9 pmol/l (mean +/- SEM); gamma LPH, 18.6 +/- 1.0 pmol/l; beta END/beta LPH, 10.0 +/- 1.1 pmol/l; cortisol, 599 +/- 55 nmol/l. Neither procedure significantly increased the plasma concentration of ACTH or any other peptide, whereas plasma cortisol was significantly increased at both 5 min and 10 min. Plasma ACTH was positively correlated with plasma gamma LPH (r = 0.701; P less than 0.001), beta END/beta LPH (r = 0.970; P less than 0.001) and plasma cortisol (r = 0.758; P less than 0.05). 4. The present study demonstrates that, in normal man, plasma endorphins do not change with experimental ischaemic pain. The rise in plasma cortisol without concomitant rise in ACTH is not explained, but suggests the action of some other agent at the level of the adrenal cortex.
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PMID:The response of plasma immunoreactive adrenocorticotropin, beta-endorphin/beta-lipotropin, gamma-lipotropin and cortisol to experimentally induced pain in normal subjects. 628 7

We have assessed the role of mefenamic acid, a non-steroidal anti-inflammatory drug known to inhibit both the synthesis and actions of prostaglandins, as an analgesic in migraine by comparing it with the established analgesic paracetamol (acetaminophen) in a double-blind cross-over trial. Forty ambulant migraine patients were supplied with oral medication for six consecutive attacks; metoclopramide 10 mg was administered in all attacks, and paracetamol 500 mg and mefenamic acid 500 mg for three attacks each. The patients recorded the intensity of the headache at the time the medication was taken, and again after 3 hours, on a linear analogue scale. Twenty-two patients completed the trial satisfactorily. Seven had insufficient attacks and the remainder were lost to follow-up. The mean reduction in headache intensity was 36 +/- 11% on mefenamic acid and 27 +/- 10% (both mean +/- SEM) on paracetamol. While this difference is not quite statistically significant (0.1 greater than P greater than 0.05) there still remains a 28% probability that mefenamic acid is twice as potent as an analgesic. The responses in each individual patient to the two drugs were very closely correlated (P much less than 0.001). Our failure to demonstrate a convincing difference between the two analgesics leads us to speculate that peripheral prostaglandin mediated pain pathways, in which paracetamol is inactive, may be less important than central pathways, which are inhibited by both drugs.
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PMID:Double blind comparison of mefenamic acid and acetaminophen (paracetamol) in migraine. 634 93

Sixty-nine women with a convincing complaint of menorrhagia took part in a double-blind treatment trial. Menstrual blood loss was measured and the subject's own perception was carefully recorded. Only 38% had objective menorrhagia with a measured loss greater than 80 ml although 59% would qualify with an upper limit of normal of 60 ml. Overall the measured loss in the "heaviest" periods (69.6 +/- 7.3 ml; mean +/- SEM) were significantly greater than that of the "lightest" periods (42.7 +/- 4.7 ml; p less than 0.001), but there were many major errors in perception by individuals. Perceived daily blood loss volume on a 4-point rating scale gave the following group means and ranges: spotting, 2.5 ml (0.1 to 15.5); light, 5.7 ml (0.1 to 63.1); moderate, 16.1 ml (0.5 to 108.6); very heavy, 22.0 ml (1.4 to 215.8); very wide individual ranges of assessment are illustrated. As a whole the group was also able to distinguish between a day-to-day volume increase or decrease, but again there were many major errors. Some subjects who experienced a reduction in measured blood loss from one day to the next actually perceived this as a large increase. Menstrual pain and duration of bleeding were not found to influence perception of blood loss volume, whereas younger subjects (26 and under) were significantly more likely than older women (37 and over) to regard a moderate loss as very heavy. There was no significant correlation between the number of pads/tampons used and the measured menstrual loss, and some individuals showed extreme variations between blood loss and pad usage. This study suggests that the only reliable assessment of menstrual blood loss volume and changes in volume in women complaining of menorrhagia is obtained by objective measurement of blood loss by a technique such as alkaline hematin extraction.
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PMID:A preliminary study of factors influencing perception of menstrual blood loss volume. 638 Feb 94

The influence of oral carbenoxolone sodium (50 mg X 3 daily) on prostaglandin E2 release into gastric juice has been examined in nine peptic ulcer patients (duodenal ulcer, n = 6; prepyloric ulcer, n = 1; gastric ulcer, n = 2) during modified sham feeding and following bolus stimulation of acid secretion by pentagastrin (6 micrograms/kg). Carbenoxolone increased the overall mean of prostaglandin E2 concentrations in gastric juice following modified sham feeding by 32 +/- 9% (mean +/- SEM; P less than 0.02) and decreased the acidity slightly but significantly (P less than 0.05). A marked rise in prostaglandin E2 levels (46 +/- 11%; n = 5; P less than 0.02) was observed in for duodenal ulcer patients and the patient with a prepyloric ulcer responding to therapy (i.e., pain relief and ulcer healing within 4 weeks of treatment). A significant peak (P less than 0.05) related to modified sham feeding was observed only during medication, while a late gradual increase in prostaglandin E2 levels--not associated with vagal stimulation--occurred both in control and carbenoxolone experiments. No significant differences were observed following pentagastrin stimulation. The initial peak in prostaglandin E2 levels observed during medication favours the notion that the mechanism of drug action relies on inhibition of enzymatic degradation while the late increase in prostaglandin E2 levels may be explained by artificial prostaglandin formation during the aspiration procedure.
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PMID:Effect of carbenoxolone on gastric prostaglandin E2 levels in patients with peptic ulcer disease following vagal and pentagastrin stimulation. 641 22

Characteristics of primary (within the area of injury) and secondary (outside the area of injury) hyperalgesia were determined after a heat injury applied to the glabrous skin of the hand in 8 human volunteers. The heat injury consisted of two burns (53 degrees C, 30 s) applied over an area 7.5 mm in diameter separated (centre to centre) by a 2 cm interval. Following the injury, a zone of hyperalgesia to mechanical stimuli measuring 20.1 +/- 3.6 cm2 (mean +/- SEM) developed in an area surrounding and including the burns. Within this zone, the pain threshold for mechanical stimuli decreased significantly by a similar amount for all areas tested (12.0 +/- 1.1 bars to 5.2 +/- 0.5 bars). Hyperalgesia to heat occurred only within the area of the burns. The heat pain threshold decreased and total ratings of heat pain increased significantly. In contrast, there was decreased pain to heat stimuli between the two burn sites, and no change in painfulness of the heat stimuli at other areas within the zone of hyperalgesia to mechanical stimuli. Particularly notable was the coexistence of hypalgesia to heat stimuli and hyperalgesia to mechanical stimuli in the uninjured region between the two burn sites. These results indicate that the characteristics of primary and secondary hyperalgesia differ and also suggest that the mechanism for hyperalgesia to mechanical and thermal stimuli differ.
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PMID:Evidence for different mechanisms of primary and secondary hyperalgesia following heat injury to the glabrous skin. 650 13

Epidural (E.D.) and intrathecal (I.T.) morphine (M) analgesia were studied in patients with pain after thoracotomy. The role of the pharmacokinetic properties of M. for the associated analgesia was also evaluated. M. concentrations in CSF and plasma were assayed using gas chromatography with EC detection. Analgesia was evaluated as the time postoperative until the patients again required analgetics and were given meperidine intramuscularly (I.M.) for thoracic pain. A lumbar site of E.D. and I.T. injection of M. resulted in a variable but in general longlasting postoperative analgesia although delayed after I.T. administration. The mean duration of analgesia after E.D. administration was dose-related (8.6 +/- 2.0 h, 13.0 +/- 3.5 h, and 15.6 +/- 2.6 h; means +/- SEM for the 2, 4 and 6 mg groups, respectively), which was comparable to that achieved after I.T. administration of 0.25 to 0.50 mg M. M. concentrations in plasma after E.D. administration were comparable in variability and magnitude to those found after I.M. administration. The concentrations of M. in plasma were not related to the long duration of analgesia and may only contribute to analgesia shortly after the E.D. administration. The reported time course of analgesia after E.D. injection with a delayed onset corresponded with the appearance of M. in the CSF. Fifteen min after E.D. administration, M. was found in higher concentrations in CSF than in plasma, but peak levels were not seen until 2 h after the injection. Both the high content of M. in CSF as expressed by AUC, as well as peak concentrations in CSF, were related to the longlasting analgesia after E.D. administration. A protracted clearance of M. from the CSF as a cause of longlasting analgesia was not found, M. was eliminated with a similar half-life from CSF and plasma. The high CSF concentrations of M. seen after E.D. administration were the result of a direct uptake across the dura. In contrast, the appearance of M. in CSF after I.M. administration of 10 mg was slower. Maximal concentration of M. in the CSF was reached after 3 h and the peak levels were on average about 100 times less than those found after E.D. injection of 6 mg morphine. CSF and plasma reached pseudoeliquilibrium at a ratio around 0.9 after I.M. administration. This is to be compared with a CSF/plasma concentration ratio around 100 after E.D. administration. A comparison of M. concentrations in the CSF after thoracic and lumbar E.D. injection showed that spinal CSF rapidly yielded comparable concentrations at the lumbar level.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Pharmacokinetic aspects of spinal morphine analgesia. 658 39

To determine whether epidural anesthesia during labor affects maternal circulating catecholamines, blood samples were obtained from 15 patients at the peak of and immediately after two consecutive painful contractions. A lumbar epidural local anesthetic without epinephrine was then administered. After the onset of analgesia, four blood samples were again drawn. All samples were analyzed by a radioenzymatic assay for epinephrine and norepinephrine concentrations. Before anesthesia, the mean (+/-SEM) plasma epinephrine level was 280 +/- 49 pg/ml, and the mean norepinephrine level was 866 +/- 122 pg/ml. After anesthesia, epinephrine levels decreased 56% (p less than 0.01). Although norepinephrine levels decreased approximately 19%, this reduction was not statistically significant. At the height of a contraction, catecholamine levels did not differ significantly from those occurring between contractions. Lumbar epidural anesthesia during labor reduces maternal epinephrine levels, probably by eliminating the psychological and physical stress associated with painful uterine contractions or by denervating the adrenal medulla. Whatever the mechanism, reducing pain and activity of the sympathetic nervous system should increase uterine blood flow.
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PMID:Maternal catecholamines decrease during labor after lumbar epidural anesthesia. 661 80


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