Pain responses in Nepalese porters.

When tested by the method of limits, Nepalese had much higher pain thresholds to electrical stimulation than Occidentals did. Discriminability was the same for both groups, however, indicating that there were no neurosensory differences. Nepalese had higher (stoical) criteria for reporting pain but were not less sensitive to noxious stimulation. The battery of sensory measurement procedures described may be applied to any modality and are particularly applicable to difficult field conditions.

Rate-limiting steps in steady-state intestinal absorption of trioctanoin-1-14C. Effect of biliary and pancreatic flow diversion.

During continuous intraduodenal infusion of emulsified fat in rats, a steady state of intestinal absorption is achieved. Maximal steady-state absorption of trioctanoin, a medium-chain triglyceride (MCT), by unanesthetized, restrained rats was found to be the same after total bile diversion as in controls (1560 mumoles of fatty acid per hr).After pancreatic and bile diversion, absorption of MCT was still one-third as rapid as in controls, and mucosal uptake apparently occurred in the form of unhydrolyzed triglyceride. Returning bile to the intestinal lumen during pancreatic diversion did not increase the absorption rate.From intestinal tissue lipid-(14)C concentrations measured during steady-state maximal absorption it was possible to calculate turnover times for labeled lipid passing through the mucosal cells. Mucosal turnover times of about 4 min for control and bile-diverted rats, and about 20 min for animals with pancreatic diversion were obtained. The rate-limiting step in octanoic acid absorption in control and bile-diverted rats was probably mucosal penetration. During absorption of unhydrolyzed triglyceride by pancreatic flow-diverted rats, both passage from the lumen into the mucosal cell and intracellular lipolysis were rate-controlling factors.

Inhibition of steady-state intestinal absorption of long-chain triglyceride by medium-chain triglyceride in the unanesthetized rat.

Maximal steady-state intestinal absorption rates in unanesthetized rats for triolein, a long-chain triglyceride, and for trioctanoin, a medium-chain triglyceride, are known to differ. Both these lipids are hydrolyzed in the intestinal lumen but the products of hydrolysis are metabolized differently by the mucosal cell. Intraduodenal infusion of trioctanoin was found to reduce steady-state triolein absorption. Luminal lipolysis was shown not to be rate-controlling. High rates of trioctanoin infusion significantly lowered the pH of the luminal aqueous phase and altered the partition of oleic acid between aqueous and oil phases. Two possible mechanisms for the inhibition of triolein uptake are considered. In the intestinal lumen medium chain lipids might have lowered the activity of oleic acid monomers in the aqueous phase and reduced passive diffusion into mucosal cells. Alternatively, competition between long and medium chain fatty acids for some common receptor during transport into the intestinal mucosal cell may have occurred. Despite significant inhibition of triolein absorption by high levels of trioctanoin, the maximum number of calories absorbed from mixtures of triglycerides exceeded the maxima from either glyceride alone. The optimum proportion of triolein to trioctanoin in lipid infusion mixtures was about 3:4 by weight and the optimum dosages about half maximal for each triglyceride, which represented a caloric intake of 4 kcal/rat per 2 hr. The absorption coefficient for this lipid mixture was about 90%. It is suggested that in patients who have a limited intestinal absorptive capacity dietary fat intake might be doubled with a caloric supplement of medium-chain triglycerides without increase in steatorrhea of long-chain fat.

Utilization of individual lecithins in intestinal lipoprotein formation in the rat.

To determine the molecular species composition of lecithins of different nascent lipoproteins, high density lipoproteins (HDL), very low density lipoproteins (VLDL), and chylomicrons (CM) were isolated from the mesenteric lymph of rats. Lymph was collected at 0 degrees C with 5,5'-dithiobis-2-dinitrobenzoic acid added to inhibit lecithin-cholesterol acyl transferase. CM were separated by ultracentrifugation and HDL from VLDL by dextran SO4-MG+2 precipitation. Molecular species of lecithin were directly isolated by reverse phase high performance liquid chromatography. In fasted animals, the lecithin compositions of lymph HDL and VLDL were virtually the same and closely resembled the lecithin composition of intestinal mucosa. When bile lecithin was eliminated (by bile diversion), there was a marked change in lecithin composition of all lipoprotein and mucosal samples, which was most notable for a reduction in 16:0-species (which are predominant in bile) and a relative increase in the corresponding 18:0-species. Feeding unsaturated triglycerides (triolein, trilinolein, or a combination of triolein and trilinolein) also resulted in a change in HDL and VLDL lecithin composition. The effect was similar whether bile lecithin was present or eliminated and was notable for a reduction in 16:0-species, an increase in 18:0-species, and the emergence of large amounts of diunsaturated lecithins that corresponded to the fatty acid composition of the triglycerides fed (i.e., 18:1-18:1, 18:2-18:2, and 18:1-18:2 lecithins). When bile-diverted rats were infused via the duodenum with a mix of [14C]choline-labeled lecithins (isolated from the bile of other rats), the incorporation of infused lecithins into different lymph lipoproteins was distinctly different. Individual lecithins were incorporated to a variable extent into each lipoprotein. In fasted rats the specific activities of all major molecular species of lecithin were relatively greater in VLDL than HDL, indicating that HDL derived proportionately more of its lecithins from an endogenous pool than did VLDL. Feeding triolein changed the specific activities of more of the lecithin species of VLDL than of HDL. The specific activities of lecithins in CM were more similar to VLDL than to HDL after triolein feeding. Results thus indicate that, although the lecithins of different mesenteric lymph lipoproteins are similar and may be derived from membrane sites with the same lecithin composition, lecithins incorporated into different lipoproteins originate from different metabolic pools and/or by different mechanisms.

Phosphatidylcholine composition of emulsions influences triacylglycerol lipolysis and clearance from plasma.

Sonicated emulsions containing triolein, a specific phosphatidylcholine and cholesterol were prepared. Bolus doses were injected intravenously into rats and plasma clearance kinetics and organ uptakes were determined. Emulsion triacylglycerol lipolysis by rat heart lipoprotein lipase was measured in vitro. Phosphatidylcholine molecular species influenced emulsion metabolism in vivo and in vitro. Emulsions containing saturated phosphatidylcholines at temperatures below their melting points were poor substrates for lipoprotein lipase, compared with those stabilized by mixed chain phosphatidylcholines. Distearoylphosphatidylcholine stimulated hepatic uptake compared with emulsions made with egg yolk phosphatidylcholine, which modeled chylomicrons closely. Emulsion populations with the same surface compositions but with mean diameters of 700-800 A and 1100-1300 A were metabolized similarly, suggesting that, within the normal chylomicron size range, size alone does not determine the disposition of triacylglycerol-rich emulsions or lipoproteins.

Composition of lymph chylomicrons from proximal or distal rat small intestine.

The composition of lymph chylomicrons secreted by rat proximal and distal small intestine were compared during constant perfusion of a lecithin-stabilized tri (1-14C) oleoyl glycerol emulsion, in pairs of unanesthesized rats with mesenteric lymph fistulas. By the 6th hr of infusion when 14C-triglyceride output was constant, the distal intestine secreted 33% less chylomicron phospholipid. Distal chylomicrons were larger and had higher triglyceride:phospholipid and higher apoprotein:phospholipid ratios than chylomicrons secreted by proximal intestine. The major apoprotein classes--apoB, apoA-I, apoE(= ARP), and C peptides--were present in both groups of chylomicrons, but in different proportions. Distal chylomicrons contained less apoA-I and more C peptides, with an increase in apoC-III3, and a decrease in apoC-III0, compared with proximal chylomicrons. The present study suggests that the distal intestine is defective in the utilization of phospholipid from the intestinal lumen for chylomicron phospholipid synthesis. Whether the observed changes in the size and phospholipid or apoprotein content of distal chylomicrons affect their system metabolism is presently not known.

Regional variation in glycolytic enzyme adaptation to dietary sugars in rat small intestine.

This investigation evaluated the adaptive response of the glycolytic enzymes, fructose-1-phosphate aldolase, fructose-1, 6-diphosphate aldolase, and pyruvate kinase, to dietary sugars throughout the small intestine. In addition, the effect of prior diet on this adaptive response and on the enzyme distribution pattern along the small intestine was studied. Rats were fed 40% glucose, 68% sucrose or carbohydrate-free diets for 6 days (baseline diet), followed by one of three isocaloric test diets (40% glucose, 68% sucrose or carbohydrate-free for 3 days. In other groups of tats isocaloric diets of 68% glucose, 68% fructose or 34% glucose + 34% fructose, fed for 4 days, were compared. Enzymes were assayed in the mucosa of the duodenum (D),and in 5 equal (by length) segments from the Ligament of Treitz to the ileocecal valve (J1, J2, J3, I1 and I2). Enzyme specific activities were significantly higher in the proximal (D-J1-J2) than distal segments (J3-I1-I2) on all diets (P smaller than 0.001). Enzyme activities after test diet periods were determined only by the test diet, and were independent of the baseline diet for all segments. The 68% carbohydrate diets increased enzyme activities significantly more (P smaller than 0.001) than the 40% glucose or carbohydrate free diets, in all segments. On the 40% glucose diet, activities were significantly higher (P smaller than 0.05) than on the carbohydrate free diet in D and J1, but not distally. The data suggest that there is an intrinsic gradient of enzyme activity from the proximal to the distal small intestine which persists despite dietary manipulation, and that all segments of the small bowel show adaptive increases to dietary sugars.

The nature of the myenteric infiltrate in achalasia: an immunohistochemical analysis.

Achalasia is an esophageal motor disorder characterized by abnormal relaxation of the lower esophageal sphincter and absence of progressive peristalsis in the esophageal body. Previous studies evaluating esophagomyotomy and esophageal resection specimens have shown the presence of myenteric inflammation to be a consistent and early pathologic change in patients with achalasia. Thus, the goal of this study was to determine the immunohistochemical characteristics of the inflammatory infiltrate within the myenteric plexus in patients with clinically early and end-stage achalasia. Using formalin-fixed tissue, we analyzed the immunohistochemical features of the myenteric lymphocytes using antibodies that recognize B cells (CD20), T cells (CD3), T cell subsets (CD8), and the activation state of T cell subpopulations (TIA-1 and granzyme B) in nine patients with clinically early achalasia who underwent esophagomyotomy and 13 patients with clinically endstage achalasia who underwent esophageal resection. The myenteric infiltrate in all nine esophagomyotomy specimens was composed predominantly of T cells (CD3-positive), the majority of which also stained for CD8. In five of nine specimens, the majority of CD8-positive cells stained for TIA-1. In the esophageal resection specimens, the myenteric infiltrate was composed predominantly of CD3-positive T cells in seven of 13 cases. In three cases, there was a predominance of CD20-positive B cells, and in the remaining three cases there were relatively equal numbers of T and B cells. In eight of 13 cases, the majority of T cells stained for CD8. TIA-1 immunoreactivity was found in the majority of CD8-positive cells in nine of 13 cases. In all esophagomyotomy and esophageal resection specimens studied, rare granzyme B-positive cells were detected. In conclusion, the majority of myenteric inflammatory cells in patients with achalasia are CD3-positive T cells, most of which are also CD8-positive, although the relative percentage of such cells appears to decrease with disease progression. Furthermore, many of the CD3-positive/CD8-positive myenteric lymphocytes also express TIA-1, suggesting they are resting or activated cytotoxic T cells. The immunohistochemical demonstration of granzyme B in a subpopulation of these cells supports the contention that achalasia is an immune-mediated disease, although the inciting antigen remains an enigma.

Squamous mucosal alterations in esophagectomy specimens from patients with end-stage achalasia.

Achalasia is an esophageal motor disorder in which the primary morphologic changes are found in the myenteric plexus. However, a number of secondary alterations are characteristically found in esophagectomy specimens, including the mucosa. In addition, these patients are at increased risk of developing esophageal squamous cell carcinoma. We studied the squamous mucosal alterations in 35 esophagectomy specimens from patients with end-stage achalasia and compared them with those found in the squamous mucosa near the esophagogastric junction from pediatric autopsies (

Esophagectomy with gastric reconstruction for achalasia.

PURPOSE: Achalasia is a degenerative esophageal disorder that may result in esophageal failure necessitating resection for restoration of gastrointestinal function. This study evaluates a protocol of esophageal resection and gastric reconstruction for end-stage achalasia. METHODS: Hospital records, radiographic studies, and resection specimens of patients undergoing esophagectomy and gastric reconstruction were reviewed. Patient outcome was defined by an evaluation of symptoms (early satiety, dysphagia, regurgitation, and reflux), dietary restrictions, and ability to maintain or gain weight. Preoperative, operative, and postoperative variables and pathologic features in the resection specimens were analyzed to determine predictors of outcome. RESULTS: In a 10-year period, 32 patients underwent esophagectomy with gastric reconstruction for achalasia; 30 (94%) underwent elective surgery and 2 (6%), emergency surgery. No postoperative deaths occurred. Of 29 patients completing telephone interviews, 24 (83%) had no or mild dysphagia; 21 (72%), no or mild regurgitation; 20 (69%), no or mild reflux; and 19 (66%), no or mild early satiety. Twenty-four (83%) patients had no or minimal dietary restrictions; 26 (90%) had no or minimal social dietary restrictions. Postoperative weight was not different from preoperative weight. Of 30 patients, 26 (87%) felt better after esophagectomy and 25 (83%) would have the operation again. There were few predictors of outcome. Younger patients were more likely to have dysphagia ( P =.03). CONCLUSIONS: Esophagectomy with gastric reconstruction relieves preoperative dysphasia and regurgitation in the majority of patients. Dietary function and weight maintenance are excellent, attesting to the durability of the procedure in patients with end-stage achalasia.

Confirmation of gentamicin and neomycin in milk by weak cation-exchange extraction and electrospray ionization/ion trap tandem mass spectrometry.

A new procedure for the confirmation of two aminoglycoside antibiotics in milk was developed and validated. This work is among the early applications of ion trap mass spectrometry for regulatory methodology, and it incorporates a novel weak cation-exchange extraction. The procedure was validated for the confirmation of both gentamicin and neomycin at 30 ng ml(-1) and above. Milk is first treated with acid and centrifuged. The supernate, excluding the fat layer, is buffered with sodium citrate to neutral pH. The extract is applied to a weak cation-exchange solid-phase extraction column. Aminoglycosides are eluted with acidified methanol. Following separation by ion-pair liquid chromatography, analytes are ionized with an electrospray interface. Protonated molecular ions are selectively stored in an ion trap mass spectrometer, then collisionally dissociated to yield unique product ion spectra. Confirmation is based on matching spectral responses between samples and comparison standards consisting of a bona fide standard spiked into control extracts. Method performance was demonstrated with replicate samples of control milk, fortified milk, and milk containing incurred residues of each compound.

Transcostovertebral approach for thoracic disc herniations.

OBJECT: The authors describe a new posterolateral transcostovertebral approach for the removal of herniated thoracic discs. METHODS: From January 1994 to January 2000, 28 thoracic discs in 22 patients were excised via a new transcostovertebral surgical approach. Seventeen patients (77%) presented with axial pain, 14 (64%) with radicular pain, 13 (59%) with myelopathy, eight (36%) with sensory loss, and 10 (45%) with genitourinary (GU) symptoms such as urinary hesitancy or incontinence. The affected discs were approached using a midline incision to gain access of the costovertebral junction. The surgical corridor was posterolateral; the costovertebral joint and lateral edge of the vertebral endplates were drilled to expose the lateral annulus. The ribs were preserved, obviating the need for insertion of a chest tube postoperatively. The average operating time per level was 200.5 minutes (range 90-360 minutes). The average blood loss was 231 ml (50-750 ml). The average length of stay was 3.8 days. Most patients were discharged home on postoperative Day 2 or 3. No patients were worse postoperatively. Improvement was demonstrated in 13 (76%) of 17 patients with axial pain, 11 (79%) of 14 patients with radicular pain, 11 (85%) of 13 patients with myelopathy, seven (88%) of eight patients with sensory loss, and six (60%) of 10 patients with GU symptoms. CONCLUSIONS: This procedure is well suited for any thoracic disc level and offers several advantages over the traditional costotransversectomy or transthoracic approaches: shorter operating time, less blood loss, less extensive soft-tissue and bone dissection, reduced postoperative pain, and shorter hospital stays.

Preoperative Multidimensional Affect and Pain Survey (MAPS) scores predict postcolectomy analgesia requirement.

OBJECTIVES: One aim of this study was to evaluate the relation of scores on the Multidimensional Affect and Pain Survey (MAPS) that was administered before surgery to postoperative morphine consumption and patient-controlled analgesia. A second aim of the study was to compare the ability of MAPS administered postsurgery with the commonly used Numerical Pain Rating Scale to predict patient-controlled analgesia behavior. DESIGN: The MAPS questionnaire measures pain, suffering, and well-being. It was administered to patients 1 day before and 1 day after left hemicolectomy for colon cancer. The relations of the two scores to postoperative pain control were determined. PATIENTS: Thirty-four patients in the surgical ward of a general hospital admitted for colorectal cancer surgery participated in this study. RESULTS: High preoperative MAPS scores on sensory and emotional words predicted postoperative morphine dosage, dose presses, and lockout presses. Greater morphine consumption was correlated positively with high presurgery MAPS scores in four of the eight "Suffering" subclusters (Depressed Mood, Anger, Anxiety, and Fear). High presurgery MAPS scores in 13 of the 17 "Sensory Qualities" subclusters (e.g., Bothersome, Intense Pain, Pain Extent, Incisive Pressure, Traction/Abrasion) were correlated positively with lockout presses. Neither the postsurgery MAPS nor the postsurgery Numerical Pain Rating Scale predicted patient-controlled analgesia behavior. CONCLUSION: The emotional states and attitudes of the patients toward pain before surgery are important factors in determining patient-controlled analgesia pressing behavior and postoperative demand for analgesics.

Triolein-phosphatidylcholine-cholesterol emulsions as substrates for lipoprotein and hepatic lipases.

Lipolysis of emulsified glycerol tri[9,10-3H]oleate by lipoprotein lipase purified from bovine milk (E.C.3.1.1.34) and by hepatic lipase purified from rat liver perfusate was studied as a function of the phosphatidylcholine molecular species and the cholesterol content of the emulsions. Overall, the activities of the two enzymes were similar on a molar basis. Lipoprotein lipase initial lipolysis rates also were comparable for emulsions made with egg phosphatidylcholine or with saturated (dimyristoyl, dipalmitoyl and distearoyl) phosphatidylcholines when cholesterol was low. Increasing the cholesterol content of the emulsion from 2-3 mole percent to 7-14 mole percent reduced triolein lipolysis by lipoprotein lipase in emulsions made with saturated phosphatidylcholines. Rat hepatic lipase was more sensitive to increased cholesterol in emulsions made with saturated phosphatidylcholines than was lipoprotein lipase. The ability to maintain triolein lipolysis during longer incubations differed strikingly among the emulsions and for the two enzymes. Lymph chylomicrons were better substrates for both enzymes than any of the emulsions.

Activities of Pu and Am isotopes and isotopic ratios in a soil contaminated by weapons-grade plutonium.

An accident and fire at the former McGuire Air Force Base and Boeing Michigan Aeronautical Research Center (BOMARC) site in New Jersey resulted in dispersion of weapons-grade plutonium in particulate form to the local environment. Soil samples collected at the BOMARC site were measured for their activities and isotopic ratios of Pu and Am isotopes by radioanalytical techniques. The activities of the Pu and Am isotopes in the BOMARC soil were markedly higher than fallout levels, and they decreased nearly exponentially with increasing particle size of the soil. The measured (241)Am activity was compared to calculated values based on decay of (241)Pu. The activity ratios of (238)Pu/(239,240)Pu, (241)Pu/(239,240)Pu, and (241)Am/(239,240)Pu observed in the BOMARC soil were much lower than those attributed to nuclear reprocessing plants and Chernobyl fallout. From the activity ratios of (241)Pu/(239,240)Pu and (241)Am/(239,240)Pu, the origin of the Pu isotopes was identified as weapons-grade and the time since production of the material was estimated. Furthermore, the atomic ratio of (240)Pu/(239)Pu in the BOMARC soil was remarkably lower than the fallout value influenced by nuclear weapons testing and the Chernobyl accident. The atomic ratio of (240)Pu/(239)Pu was very close to the value of the weapons-grade Pu detected from the Thule accident in Greenland. This work demonstrates the utility of radioanalytical measurements and decay calculations for defining characteristics of the source term and discriminating multiple processes that contribute to a source. Such an approach would also be needed to respond to a terrorist event involving an improvised nuclear device or radiological dispersal device.

Chylomicron composition during duodenal triglyceride and lecithin infusion.

In lymph fistula rats infused intraduodenally with trioleoylglycerol emulsions, the secretion of triglyceride was enhanced and that of total and esterified cholesterol in chylomicrons was strikingly reduced when lecithin was added at 4-5 times the biliary lecithin secretion rate. During continued triglyceride secretion in the presence of lecithin, the phospholipid: unesterified cholesterol ratio of the chylomicrons increased significantly in contrast to lecithin-free emulsions. Bile-diverted lymph fistula rats secreted significantly less esterified and total cholesterol in lymph chylomicrons than controls, and the difference was magnified by lecithin administration. Cholesterol appears to become relatively unavailable for incorportion into chylomicrons when lecithin is administered at high rates.

Mucosal coenzyme A-dependent cholesterol esterification after intestinal perfusion of lipids in rats.

Coenzyme A-dependent esterification of cholesterol was determined in intestinal mucosal homogenates prepared after duodenal perfusion of cholesterol-free lipid emulsions for 5 h in unanesthetized rats. Cholesterol esterification rates were lowest and the mucosal cholesterol pool was greatly reduced after the same lipid infusions that, in lymph fistula rats, had produced chylomicrons deficient in cholesterol esters. CoA-dependent esterification rates were sufficient to account for all the cholesterol esters secreted in mesenteric lymph chylomicrons. During triglyceride secretion by the gut, unesterified cholesterol for chylomicron membranes may be maintained both by suppressing mucosal CoA-dependent cholesterol ester formation and from a mobilizable unesterified cholesterol pool within the mucosa.

The uptake of oleic acid by rat small intestine: a comparison of methodologies.

The interaction between long-chain and medium-chain lipids during intestinal absorption was examined using several model systems. A decrease in steady-state triolein (LCT) output in thoracic duct lymph after addition of trioctanoin (MCT) to the duodenal infusion confirmed previous studies in unanesthetized rats which demonstrated inhibition of steady-state LCT uptake from the small intestinal lumen by MCT. In slices of everted rat jejunum octanoic acid reduced incorporation into triglyceride and initial uptake of (14)C-labeled oleic acid from micellar solutions. Inhibition of uptake did not occur at 0 degrees C, when triglyceride synthesis was blocked. Incubation of slices at low pH (5.8) or in the presence of dimethyl sulfoxide also reduced uptake of oleic acid and its incorporation into triglyceride. However, when everted sacs of jejunum were similarly incubated, octanoate, dimethyl sulfoxide, or low pH caused no inhibition of oleic acid uptake or esterification. The results indicate that the significance of kinetic data describing intestinal fatty acid absorption which were obtained from experiments conducted in vitro is highly questionable, and that suitable models for in vivo uptake kinetics have yet to be developed. However, analysis of the in vitro kinetic data suggests that the intestinal mucosal membrane does not function as a simple lipid interface with respect to fatty acid absorption.