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Biochemical, immunological and epidemiological evidence increasingly support the suggestion that there is a causal relationship between gluten/gliadin and schizophrenia as originally proposed by F. C. Dohan. Furthermore the necessary physiological mechanisms exist to explain a mechanism involving bioactive peptides from these proteins, and these show that this mechanism is possible and probable in at least in a substantial subgroup of schizophrenic patients. Evidence shows a fairly strong genetic disposition, and it must be recognised that any genetic mechanism must implicate altered chemistry and function of proteins. Evidence supports the likelihood that dietary intervention is beneficial for some, and this demands further investigation. A similar conclusion may apply to autism spectrum conditions.

We have investigated the possible benefits of elemental diets, especially a diet supplemented with L-glutamine, on maintenance of intestinal absorptive function in rat small intestine damaged by 5-fluorouracil. Although a standard rat diet sustained better body growth in control rats, each of the elemental diets and the diet containing intact casein in place of hydrolyzed casein was beneficial in promoting less body weight loss during the 3 d after 5-fluorouracil injection. The same significant benefit was seen in absorptive activity measured in small intestine in vitro 3 d after the cytotoxic injury. Glutamine supplementation, however, did not confer any significant advantages, although it did cause significant elevation of muscle glutamine pools. This elevation was substantially less than the corresponding increase in muscle glycine content after dietary supplementation with glycine.

Human melanocytes established in MCDB-153 culture medium do not express alpha 1-, beta 1-, beta-2 adrenoceptors without extracellular stimulation. The addition of 50 x 10-9 M norepinephrine to the medium causes a time-dependent induction of alpha-1-adrenoceptors with 4.278 receptors/melanocyte after 24 h. Under the same experimental conditions, the dendricity of melanocytes as well as melanogenesis was unaffected over 60 h. Since keratinocytes hold the full capacity for catecholamine biosynthesis but melanocytes lack this system, the secretion of catecholamines from keratinocytes appears to be of critical importance to the alpha-1-adrenoceptor in melanocytes, underlining the symbiosis of both cells in the epidermal unit.

We have optimized a method for measuring total hydroxyproline (HYP) in urine by HPLC after release from urinary peptides by solid-phase hydrolysis on Dowex 50W x 8 ion-exchange resin. The HYP was derivatized with 4-chlor-7-nitrobenzo-2-oxa-1,3-diazole, and excess reagent was removed with the use of a 100-mg C18 Bond-Elut cartridge. The HYP derivative was separated isocratically at 30 degrees C on a 250 x 4.6 mm reversed-phase column containing 5-microns particles of Spherisorb S5 ODS-2, with S-carboxymethylcysteine as internal standard. Total assay time was 14 min. The standard curve for the method was linear from the detection limit for HYP, 3.6 mumol/L, to 10 mmol/L. The between-batch CV was less than 5.1% and the mean analytical recovery of HYP was 95% +/- 1.4%. Comparison with a commercially available colorimetric method showed good correlation: y = 1.158x + 19.76 mumol/L (Syx = 74, n = 120), but HPLC results were 15% higher, probably from incomplete hydrolysis with the colorimetric method. This method offers a considerable improvement in assay time, specificity, sensitivity, precision, and cost compared with the colorimetric method.

Rett syndrome is a neuro-developmental disorder related to autistic behavior. Persons with autism have previously been found to have hyperpeptiduria. We here report a significantly higher level of peptides in the first fasting morning urine from 53 girls with Rett syndrome (both classical and congenital) compared with 53 healthy girls. This elevation in urinary peptides was similar to that in 35 girls with infantile autism. As in persons with autism, the individual levels of urinary peptides in the Rett syndrome group varied, and about a fifth were within the normal range. Levels of peptides were lower in girls with classic Rett syndrome than in girls with congenital Rett syndrome. This may be due to different etiological causes or to active and stagnant phases of the disease. Urine from girls with Rett syndrome was found to have higher frequency and higher levels of some urinary peptides that may cause inhibition of brain maturation and epilepsy.

The scientific rationale for the use of oral preparations of enzymes, such as Phlogenzyme (containing trypsin and bromelain), Mulsal-N (containing trypsin, bromelain, and papain), and Wobenzyme (containing trypsin, chymotrypsin, papain, and bromelain), for treatment of extra-gastrointestinal diseases in Man hinges critically upon the question of whether the enzymes (or a therapeutically significant amount of them) can be absorbed across the gastrointestinal tract in intact form. This is an area, formerly regarded as distinctly controversial, where opinion among gastrointestinal physiologists has changed markedly in the past two decades, and which is currently attracting renewed research activity on mechanisms of absorption. It is now accepted beyond reasonable doubt that significant (albeit small) amounts of many macromolecules can be absorbed in intact and biologically active form.

1. Healthy humans ingested the dipeptide carnosine (L-beta-alanyl-L-histidine). Their plasma levels and urinary outputs of carnosine and beta-alanine were monitored over the following 5 h. 2. Large amounts of intact carnosine (up to 14% of the ingested dose) were recovered in the urine over the 5 h after ingestion. However, carnosine was undetectable in the plasma unless precautions were taken to inhibit blood carnosinase activity ex vivo during and after blood collection. 3. The amount of carnosine recovered in urine varied substantially between subjects. It correlated negatively with carnosinase enzymic activity in the plasma. Highest carnosinase activities were observed in those subjects who regularly underwent physical training. 4. Urinary recovery of the disaccharide lactulose also varied considerably between subjects, but was substantially lower than that of carnosine. There was no significant correlation between the recoveries of carnosine and lactulose. 5. When lactulose was ingested with a hypertonic solution, the urinary recovery of lactulose was generally increased. When carnosine was ingested with a hypertonic solution, the urinary recovery of carnosine was reduced: hence the paracellular route probably is not dominant for absorption of intact carnosine. 6. Intact carnosine must have crossed the intestine to an extent much greater than hitherto recognized. Rapid post-absorptive hydrolysis is a severe obstacle to quantification of intact peptide absorption.

An HPLC method is described for simultaneously obtaining the enantiomeric ratio of three amino acids (aspartic acid, serine, and glutamic acid) from dental collagen, with a view to using this information for estimating age at death. Results are reported from a sample of twenty three known age modern teeth, six known age 19th C. AD teeth, and two unknown age Romano-British teeth. It was found (as expected) that all three D/L ratios changed significantly with chronological age. Standard calibration techniques were used to estimate ages for the six 19th C. AD specimens from regression equations estimated from the modern specimens, and also to predict (for the first time) the error associated with such estimates. Errors using aspartic acid were found to be similar to those obtained by other methods of age estimation from dental evidence, serine, and glutamic acid providing much poorer age estimates. ADditionally, a systematic difference in the age-enantiomeric ratio relationship was observed between modern and older dental samples. It is concluded that there is some fundamental difference in the observed enantiomeric ratios between modern teeth and older samples, possibly as a result of the chemical alteration of the dental proteins.

The carbon dioxide laser has been used clinically in both otorhinolaryngology and neurological surgery for approximately 10 years. Only recently, however, have technical modifications allowed its use with the operating microscope, providing the increased precision and control necessary for intracranial surgery. This paper reports the authors' experience with the carbon dioxide laser in the removal of acoustic tumors, details the surgical technique involved, and describes the advantages that may accompany the use of the laser in the removal of these difficult lesions.

The peptide, N-benzoyl-L-tyrosyl-p-aminobenzoic acid, which is used in an oral test of pancreatic function, has been perfused through isolated rat small intestine in order to determine whether it can be absorbed across the intestine in intact form, and whether it is hydrolysed appreciably by intestinal enzymes. For comparison, transport of N-benzoyl-DL-tyrosine, L-tyrosine, L-tyrosyl-L-leucine and p-aminobenzoic acid has also been studied. Very small amounts of bound tyrosine (probably mainly intact peptide plus some benzoyl-tyrosine) and of free p-aminobenzoic acid crossed the intestine during perfusion with N-benzoyl-L-tyrosyl-p-aminobenzoic acid. Adsorbed pancreatic enzymes were possibly responsible for the very small amount of hydrolysis of the peptide. However, no detectable free tyrosine crossed the intestine during perfusion with N-benzoyl-L-tyrosyl-p-aminobenzoic acid or with N-benzoyl-DL-tyrosine. In contrast, substantial quantities of free tyrosine crossed the intestine during perfusion with L-tyrosine or with L-tyrosyl-L-leucine. Net transport of tyrosine from L-tyrosyl-L-leucine was less than that from equimolar free L-tyrosine; no detectable intact L-tyrosyl-L-leucine crossed the intestine. During perfusion with free p-aminobenzoic acid the concentration in the serosal secretion apparently exceeded that in the lumen by a factor of 1.7; this suggests active transport of p-aminobenzoic acid.

Current theories of protein digestion and absorption state that free amino acids are the only significant form in which amino-N crosses the intestine and enters the systemic circulation. Nevertheless, there is now abundant evidence that intact peptides escaping digestion (or undergoing only partial digestion) and even whole protein molecules can enter the circulation in health and disease. Since peptides are now believed to play a major role in neural and endocrine regulation and in view of the fact that intestinal digestive activity can be reduced and intestinal ‘permeability’ increased in a variety of pathological conditions, the possibility that absorbed intact peptides can exert biological activities in peripheral tissues and can elicit symptoms in susceptible individuals now requires critical evaluation. These considerations may provide a physiological rationale for changing the source(s) of dietary protein in cases where food allergies/dietary sensitivities are suspected.

The effect of phenformin over a wide range of concentrations on oxidation of several subtrates by rat liver mitochondria was studied polarographically. Biphasic responses with both stimulatory and inhibitory phases were observed: their order of appearance depended on the nature of the substrate. Dose-response data for these phenomena are reported. At low phenformin concentrations ( −4 M) only stimulation occurred, while at high concentrations (> 10 −2 M) only inhibition was observed. Insensitivity to dinitrophenol and ADP suggested that the stimulation was due to progressive uncoupling. Very high concentrations of phenformin did not inhibit the oxidation of ascorbate/TMPD. Possible sites of action of phenformin are discussed. Although it is not possible to define these with certainty it appears that several sites must be involved.

Measurements of villus height, crypt depth and mucosal thickness were made for each of duodenum, jejunum and ileum of rat small intestine from animals on both unrestricted and restricted feeding regimens. Contrary to a previous report, there was no evidence for consistent or synchronized diurnal variation in villus height at any region of small intestine on any of the feeding regimes. Likewise, no diurnal variation was seen in crypt depth or mucosal thickness. Variation in villus cell numbers, therefore, cannot account for previously reported diurnal variation in absorptive and digestive activities in rat small intestine. The present results support the hypothesis that the stimulus for exfoliation is probably cell recruitment and migration up the villi.

1. Re-examination of data for the chemical analysis of peptide-bound amino acids in the mesenteric venous blood of anaesthetized guinea-pigs suggests that there are small, but significant, amounts of small peptides in the blood of fasted animals. 2. Furthermore, there is a significant increase in the peptide content of the mesenteric venous blood during intraduodenal infusion of a partial digest of casein. 3. The data are consistent with the view that some 10% of the amino nitrogen entering the mesenteric blood during absorption of a casein digest in vivo may be in the form of small peptides, although it is not possible to define confidence limits for this estimate.

1. A new preparation of isolated rat jejunum plus ileum (ca. 100 cm) is described in which a saline infusate is pumped into the superior mesenteric artery, the superior mesenteric vein having been ligated.2. The arterial infusate washes out the tissue spaces: the lumen is perfused in a single pass with a segmented flow as by Fisher & Gardner (1974).3. At an arterial infusion rate of 3 ml./min, steady states are set up in the tissue fluid within 10-15 min: the compositions of the fluids bathing both sides of the mucosa can therefore be controlled.4. The rate of glucose absorption from the lumen falls only gradually when the luminal sodium is replaced by choline abruptly while the tissue fluid sodium is maintained at 144 m-equiv/l. by arterial infusion.5. The rate of glucose absorption from the lumen is unaffected by replacement of sodium in the arterial infusate by choline.6. Ouabain (10(-4) M) in an arterial infusate containing sodium 144 m-equiv/l. causes inhibition of glucose and water absorption from the lumen. There is no effect of ouabain when the arterial infusate contains sodium, 0 or 72 m-equiv/l.7. Arterial ouabain does not reverse the effects of depletion of luminal sodium. Simultaneous removal of luminal sodium and application of arterial ouabain causes faster inhibition of glucose absorption than does either treatment alone.8. Glucose absorption is more likely to depend on rate of efflux of sodium from mucosal cell to tissue fluid than on a sodium gradient at the brush border or on intracellular sodium concentration.

1. Hydrolysis of peptides has been measured in isolated rat small intestine perfused with a pancreatic digest of lactalbumin in the presence of 2,4-dinitrophenol. 2. Although transport of water and amino acids was severely inhibited by 2,4-dinitrophenol, peptide hydrolysis to free amino acids was apparently unimpaired. 3. Only a small fraction of the hydrolysis observed could be accounted for by leakage of enzymes into the lumen. 4. The results show that the brush-border enzymes proximal to the transport mechanism(s) can be an important site of hydrolysis of peptides to amino acids under conditions where the transport of unhydrolysed peptides is inhibited. The results are consistent with the concept of membrane (contact) digestion, although the significance of intracellular hydrolysis and of transmural transport of intact peptides is also discussed.

Euryhaline fishes, such as the salmon and the eel, adapt the osmoregulatory mechanisms of their gills, kidney and intestine so that they retain water while they are in the sea but retain salt while in fresh water (e.g. Krogh, 1939). Thus on entering fresh water the osmotic pressure of plasma in the Atlantic salmon, Salmo salar L., only falls from some 410 m-osmole/1 to about 340 m-osmole/1 (calculated from the freezing point data of Benditt, Morrison & Irving, 1941), although the osmotic pressure of the environment falls from around 1000 m-osmole/1 to almost zero.

1. Glucose absorption, water absorption and dipeptide hydrolase activities have been determined in isolated rat small intestine at 1, 3, 5 and 21 days after a single intraperitoneal injection of 5-fluorouracil. 2. Absorption rates and enzyme activities were elevated 1 day after treatment, but were reduced to 40% of control values at 3 and 5 days. Changes were seen regardless of whether absorption was expressed per unit length or per unit dry weight of intestine. 3. There were highly significant positive correlations between glucose or water absorption rates and peptidase activities, especially in proximal jejunum. The most significant correlation was observed between water absorption rate and jejunal l-Leu-Gly hydrolase activity. 4. Malabsorption may account for some of the gastrointestinal side effects associated with treatment with 5-fluorouracil. Enzyme measurements may be useful as an index of intestinal function.

In order to test the hypothesis that elemental diets protect the intestinal mucosa against 5-fluorouracil toxicity, we have estimated water absorption, cytoplasmic peptide hydrolase activities, and mucosal DNA contents in isolated intestines from rats fed on one of three elemental diets or a standard diet and injected with 5-fluorouracil. Water absorption rates were significantly increased when rats, not injected with 5-fluorouracil, were fed on Flexical or Vivonex-HN. However, water absorption was severely impaired 3 days after administration of 5-fluorouracil and none of the elemental diets alleviated this impairment of absorption. Cytoplasmic peptide hydrolase activities and mucosal DNA contents were also severely decreased after 5-fluorouracil injection, the changes observed being independent of the diet. Also, none of the elemental diets reduced the body weight losses observed after 5-fluorouracil administration. Although the effects of the sodium salt of 5-fluorouracil on body weight and food intakes were much less severe than those of the Tris salt the two salts had identical effects on intestinal absorption even when an elemental diet was used. Although there was a smaller incidence of diarrhea after 5-fluorouracil administration when the rats had been fed on one of the elemental diets, diet B, the results do not support the suggestion that elemental diets might reduce the intestinal toxicity of 5-fluorouracil.

Passage of intact peptides across isolated rat small intestine has been studied during luminal perfusion with partial digests of proteins or with dipeptides. Significant passage of intact peptide does occur, the amount depending upon the luminal concentration. It probably reflects the 'digestibility' of the protein or protein digest. Previous studies are discussed and, although intact peptide transport is probably not of major nutritional importance, it is suggested that the pathophysiological significance of this process and of peptidaemia merits further attention.

Crew, A. D., Varkonyi, P. I., Gardner, L. G., Robinson, Q. L. A., Wall, E., and Deverall, P. B. (1974). Thorax , 29 , 437-445. Continuous positive airway pressure breathing in the postoperative management of the cardiac infant. Continuous positive airway pressure with spontaneous ventilation was used in the postoperative period following palliative or corrective surgery for congenital heart defects in a group of children of less than 3 years of age. After stabilization of the cardiovascular state, continuous positive airway pressure breathing (CPAP) was shown to be a suitable alternative to continuous positive pressure ventilation (CPPV). A statistically significant increase in PaO2 was observed on changing from CPPV to CPAP. A statistically significant decrease in PaO2 and increase in pulmonary venous admixture was observed after discontinuing the positive airway pressure and allowing the patient to breathe at ambient pressure. We would recommend CPAP as an intermediate manoeuvre in the withdrawal of ventilatory support as it introduces a smoothness and stability into patient management regimes which was previously lacking. Careful selection of apparatus is necessary as the airway pressure should be truly continuous and steady. In neonates the dead space of the system should be reduced to a minimum; CPAP alternating with periods on CPPV may be necessary for some time after cardiovascular stability has been attained.

The many enigmatic factors in the life cycle of the Atlantic salmon have long fascinated and long frustrated those working on this subject. This comprehensive review by Dr Michael Gardner collates and summarizes the findings of investigations from the turn of the century to the present day. The author also provides an objective assessment of several hypotheses relating to the reasons for the diverse behaviour patterns of the salmon.

Records from salmon counters at hydro-electric dams, and of angling results, in the Tay-Tummel-Garry river system are analysed. Spring runs of ascending salmon have decreased since at least 1950, but summer and autumn runs have increased since 1959. Hydro-electric developments are not responsible for these changes, nor for the decrease in the average weight of salmon in the system. Possible environmental factors are discussed, and a method suggested whereby the ratio of sizes of salmon populations in branches of a river system may be estimated. The numbers of descending kelts have recently increased, but the times of downstream migration have not changed.

Hydrolysis of proteins and peptides with mercaptoethane sulfonic acid is liable to produce overestimation of the proline content owing to the production of ninhydrin-positive material (probably cysteine) which coelutes with proline on many ion-exchange analytical systems. A similar error occurs with HCl hydrolysis (especially in the presence of mercaptoethanol or thioglycollic acid) if care is not taken to oxidize cysteine during reconstitution of the hydrolysate before amino acid analysis.

Glucose and water absorption rates are much lower (50%) in isolated perfused rat small intestine when the animals are killed by stunning or ether before removal of the intestine than when the animal is maintained alive under light ether anaesthesia throughout the setting-up procedure.

The effects of phenformin on glucose and water absorption from isolated perfused rat small intestine were studied. Luminal phenformin inhibited glocose and water absorption progressively as its concentration was increased from 0-1-1-0 mg.ml-1. At 0-5 mg phenformin ml-1, inhibition increased with time of exposure to phenformin up to 15 min and thereafter remained constant. Arterial infusion of phenformin (1-0 mg-ml-1) produced less inhibition of glucose and water absorption. The site of phenformin's action appeared to be intracellular. Phenformin absorption from a luminal perfusate (0-5 mg-ml-1) was measured. Although it was rapidly absorbed (22 microgram.cm intestine-1.h-1) from the lumen, less than 2 microgram.cm-1.h-1 appeared at the serosal surface of the intestine. In subsequent phenformin-free perfusion, only 25% of the absorbed phenformin was recovered in the luminal and serosal effluents.

1. Hydrolase activities against three dipeptides were measured in mucosal cytoplasm in unperfused intestines and in mucosal cytoplasm, luminal effluents and serosal secretions after perfusion in vitro and in vivo for 1 h. Intestines in vitro were prepared both from anaesthetized rats and from freshly killed rats. 2. Only 0·6–1·9% of the initial cytoplasmic activity was recovered in the luminal effluent when intestines in vitro were prepared from anaesthetized rats. Recoveries in luminal effluents were similar (1·3–3·3%) during perfusion in vivo. 3. Losses of dipeptidases into the luminal effluent were four to eight times greater when intestines in vitro were prepared from freshly killed animals. 4. Similar losses of dipeptidases into the secretion on to the serosal surface were observed; they too were much greater when intestines were prepared from freshly killed animals. 5. Small losses of mucosal DNA during perfusion were also observed; however, losses of cytoplasmic peptidases were consistently slightly greater. 6. Enzyme loss therefore probably occurs both by sloughing of whole cells and by a more specific process which is greatly influenced by experimental procedure. Caution is necessary in the interpretation of peptide transport experiments in vitro, although the possibility that intraluminal hydrolysis is of physiological significance must not be excluded.

To assess quantitatively the merits of internal standardization, an amino acid mixture of known composition has been analyzed by conventional automated amino acid analysis before and after being subjected to total acid hydrolysis. Both the precision (reproducibility) and the accuracy (lack of bias) were generally, but not invariably, greatly enhanced by the use of internal standardization with norleucine as opposed to external standardization. Incorporation of internal standards into samples is strongly recommended.

1. The structural integrities of various preparations of rat small intestine for the study of absorption in vitro have been compared after incubation or perfusion. 2. Perfused intestines removed from anaesthetized rats, and thus never deprived of a supply of oxygen, maintain their structural integrity even after perfusion for 1 h provided that a Krebs–Henseleit bicarbonate perfusate is used. However, intestines removed from freshly killed rats show severe villus disruption and oedema after perfusion for only 20 min. 3. Extensive damage to both crypts and villi is observed in everted sacs of small intestine incubated for 20 min, regardless of the buffer system used. Intestinal rings show damage at the tips of the villi after incubation for 2 min, but otherwise remain morphologically intact; this damage is progressive with time. 4. It is concluded that the exact mode of preparation of intestinal tissue is critical for preservation of structural and functional integrity and that this is especially important in quantitative studies on transport processes. Further, it is recommended that routine monitoring of the integrity of intestinal preparations in vitro is desirable and that histological assessment is an appropriate technique.

1. Rats injected intraperitoneally (i.p.) with the Tris salt of 5-fluorouracil (1.44 mmol/kg) showed severe toxic symptoms and a 15% mortality. No mortality and no obvious toxicity, apart from intestinal toxicity, resulted after injection of the sodium salt at equimolar dosage. 2. The plasma pharmacokinetics of the two salts of 5-fluorouracil (1.44 mmol/kg) were different after i.p. injection: higher plasma levels were achieved and were sustained for longer after the Tris salt than after the sodium salt. 3. No differences in plasma pharmacokinetics were observed after intra-arterial (i.a.) injection of the two salts of 5-fluorouracil (6.576 mmol/kg). 4. Thus there are fundamental (and potentially important) differences between the biological properties of the sodium and Tris salts of 5-fluorouracil. These cannot be explained at present.

1. 1. Published data for absorption kinetics have been fitted by non-linear regression to (i) a single Michaelis-Menten function, (ii) a Michaelis-Menten function plus a linear term and (iii) a sum of two Michaelis-Menten functions. A series of criteria have been drawn up to establish the goodness of fit in each case. 2. 2. In 17 out of 35 cases the Michaelis-Menten function was the “best fit”. In nine cases the “best-fit” model also included a linear term, but never was the sum of two Michaelis-Menten functions accepted to be the “best-fit” model. 3. 3. Linearity of a Lineweaver-Burk plot was of unreliable diagnostic value in assessing goodness of fit. 4. 4. Since the fit of a Michaelis-Menten function was often poor, simulated data sets with error were used to study the influence of experimental design etc. on Michaelis-Menten parameter estimation. 5. 5. Precision of estimation of K m is increased by increasing the number of data points, reducing their variance, increasing the data range and by straddling K m in the observations. For a given constant number of observations there is no advantage in using replicate observations at few concentrations or single values at relatively many concentrations, or in using single values rather than means. 6. 6. The caution necessary in interpretation of kinetic models is emphasized.

Water absorption, measured in vitro in the perfused rat small intestine, following injection of the Tris or sodium salt of 5-fluorouracil (5FU) has been compared with that following a food restriction regime which mimicked the food intake pattern of rats after injection of 5FU. Water absorption rates were decreased both after administration of 5FU and after food restriction but the decrease following 5FU injection was much greater. Also, the Tris and sodium salts of 5FU had different effects on the food intake pattern after injection but had very similar effects on intestinal absorption of water. Hence the effects of 5FU on absorption cannot wholly be attributed to a reduced food intake. Four reference systems have been used to express water absorption rates: whole small intestine, unit length of intestine, intestinal dry weight and mucosal DNA content. The importance of the choice of reference system is discussed. Due to the heterogeneity of the mucosal cell population the use of DNA and dry weight as reference systems could not give an unequivocal indication of whether the changes in absorption rates resulted from a change in the number of absorbing cells or from a change in the absorptive capacity of each absorbing cell. Severe systemic toxicity, including death, was observed after injection of the Tris salt of 5FU, but not after injection of the sodium salt.

1. A new technique has been developed for making serial measurements of water and solute absorption from the lumen of isolated small intestine.2. The isolated intestine is perfused in a single pass with a segmented flow of slugs of liquid separated by bubbles of oxygen-carbon dioxide mixture. Simultaneous collections are made of effluent from the lumen and of the fluid which is transported across the mucosa. This latter fluid appears to be a fair sample of the tissue fluid.3. Conditions in the lumen can be changed within less than 5 min. The effects of two or more treatments applied to the same segment of intestine can be determined and the time course of a change in luminal conditions.4. The rate of appearance of solutes on the serosal side depends on the rate of water absorption, and changes exponentially towards a steady state. The rate constant is a function of tissue fluid volume.5. In the steady state the concentration of glucose in the tissue fluid is 71 mM when the luminal concentration is 28 mM, and is 45 mM when the luminal concentration is 8.3 mM.6. For solutes such as glucose for which reflux from tissue fluid to lumen is small relative to flux from lumen to tissue fluid, the time of attainment of a steady state in secretion is usually 50-60 min.7. For solutes such as sodium for which the reflux is relatively high, the steady state may be reached in 15-20 min.8. The K(m) for glucose absorption (14-19 mM) is much lower than is found with unsegmented flow perfusion.9. These findings emphasize problems in interpreting results from other types of intestinal preparation.10. The rate of glucose absorption from the lumen falls only gradually when the luminal sodium concentration is reduced abruptly. In contrast the rate of glucose absorption falls suddenly when the luminal glucose concentration is reduced abruptly. This suggests that glucose absorption is not directly dependent on luminal sodium ions.

1. Water absorption rates by small intestine in vitro and the incidence of diarrhoea in vivo were estimated after 5-fluorouracil was injected into rats at various times of day and night. 2. Impairment of water absorption and the incidence of diarrhoea were minimal in rats on a normal dietary regimen when the 5-fluorouracil was injected at around 02.00 hours. 3. the DNA content of the mucosa of the small intestine from uninjected animals also showed a diurnal variation, with a maximum at around 03.00 hours. 4. Manipulation of the time of injections (possibly in relation to feeding time) provides a potential means for increasing the therapeutic value of 5-fluorouracil.

1. Water absorption and cytoplasmic dipeptidase activities were determined in isolated rat small intestine after animals had fed on various ‘elemental’ diets or a standard rat diet and after a single injection of 5-fluorouracil. 2. Vivonex diets were associated with a decrease in dry weight of the small intestine and an increase in glucose and water absorption in vitro. 3. The nature of the dietary nitrogen profoundly affects the activities of intestinal peptidases. 4. Water absorption was severely depressed 3 days after 5-fluorouracil administration: the extent of depression was independent of the diet. Thus, any ameliorative effects of ‘elemental’ diets on 5-fluorouracil toxicity are unlikely to be mediated by direct protection of intestinal absorption.

Although surgical removal is generally regarded as the management strategy of choice for acoustic tumors, there remains a small group of patients usually with small or intracanalicular tumors in whom nonoperative management may be a desirable alternative to operation. The authors present a series of six such cases and discuss criteria that may aid in the selection of patients suitable for initial nonoperative management.