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Aim: To determine whether cardiovascular autonomic function is impaired in systemic lupus erythematosus (SLE). Methods: A case-control study of 23 patients with SLE was performed. Autonomic symptoms were assessed using a standard questionnaire. Cardiovascular autonomic function was measured using 10 non-invasive investigations. There were significant differences between patients and controls in three out of 24 parameters measured during the different tests (P < 0.002). These were reduction in systolic blood pressure at 5min on head-up tilt, and heart rate responses to isometric exercise and cutaneous cold. Eleven out of 23 patients had an abnormal heart rate, blood pressure or Valsalva response (value below the age corrected 5th centile) while testing compared with six of the controls. Plasma adrenaline and noradrenaline levels were significantly lower in patients vs controls in both the supine (P < 0.05) and tilt position (P < 0.01). Twenty-one of the 23 patients had one or more symptoms that may be attributable to abnormalities in autonomic function. There was no significant association between the number of symptoms and presence of autonomic dysfunction. Cardiovascular autonomic impairment may be demonstrated in some patients with SLE. Symptoms attributable to autonomic dysfunction are common in SLE and autonomic assessment may be required. [ABSTRACT FROM AUTHOR]

An F2 population from a cross between barley accession Q21861 and the Australian barley variety 'Galleon' was used to develop RAPD markers for resistance to barley leaf rust (Puccinia hordei). Resistant and susceptible DNA bulks were constructed following the classification of F2 plants by leaf rust infection type. Bulked segregant analysis was then used to identify a 2.7-kb marker, designated OU022700 and located approximately 12cM from RphQ, a leaf rust resistance gene in Q21861. The marker was generated by PCR with the oligonucleotide primer OPU-02 (Operon). Infection types of F3 progeny were used to confirm assignment of F2 genotypes. OU022700 was shown, retrospectively, to be useful in the identification of individual F2 plants that had been originally misclassified as having susceptible infection types. Both the RAPD marker and RphQ will be potentially useful in the development of new barley cultivars.

The dorsal horn of the spinal cord, which forms the locus of first synapses in pain pathways, is an important site of interaction between calcitonin gene-related peptide (CGRP), substance P and enkephalin--the neuropeptides considered to be especially involved in the regulation of pain perception. Since adjuvant-induced arthritic rats provide a suitable model for peripheral inflammation and hyperalgesia, the possible alterations of immunoreactive CGRP, substance P and enkephalin as well as the binding sites for [125I]hCGRP alpha, [125I]substance P/neurokinin-1, (NK1) and [125I]FK-33-824/mu-opioid receptors were studied in the dorsal horn of the spinal cord receiving projections from the inflamed limbs. In arthritic rats compared to control animals, a bilateral increase in CGRP- and substance P-immunoreactive fibres and the presence of enkephalin-immunoreactive cell bodies were noted in the dorsal horn of the spinal cord. As for receptors, while a significant decrease in [125I]hCGRP alpha and [125I]substance P/NK1 binding sites was observed in selective layers, no measurable alteration in [125I]FK-33-824/mu-opioid binding sites was noted in any regions of the arthritic rat dorsal horn compared to the unaffected control rats. Following unilateral section of the peripheral nerve prior to induction of arthritis, CGRP- and substance P-immunoreactive fibres were markedly depleted and no enkephalin-positive neurons were observed in the ipsilateral dorsal horn. Analysis of receptor binding sites in denervated arthritic rats, however, exhibited differential responses, i.e. a significant increase in [125I]hCGRP alpha, a marked decrease in [125I]FK-33-824/mu-opioid and apparently no alteration in [125I]substance P/NK1 receptor binding sites were observed in the ipsilateral dorsal horn compared to the intact contralateral side. These results taken together provide anatomical evidence for a concerted role of these peptides in the regulation of adjuvant-induced hyperalgesia accompanying peripheral inflammation.

Elemental diet is as effective as corticosteroids in the treatment of previously untreated Crohn's disease. It is unclear whether a poor nutritional state is a prerequisite for efficacy of elemental diet, whether previously treated patients respond as well, or how duration of remission using elemental diet compares with corticosteroid induced remission. Forty two patients with active Crohn's disease were stratified for nutritional state and randomised to receive Vivonex TEN 2.1 l/day for four weeks, or 0.75 mg prednisolone/kg/day for two weeks and subsequent reducing doses. Nine of 22 (41%) patients assigned to nutritional treatment were intolerant of the diet. Thirty patients completed four weeks treatment. Disease activity decreased on elemental diet from mean (SEM) 4.8 (0.9) to 1.7 (0.6), p < 0.05, and on prednisolone from 5.3 (0.5) to 1.9 (0.6), p < 0.05. For each treatment, nourished and malnourished patients responded similarly. Patients with longstanding disease responded as well as newly diagnosed patients. The probability of maintaining remission at six months was 0.67 after prednisolone, 0.28 after elemental diet, and at one year was 0.35 after prednisolone and 0.09 after elemental diet, p < 0.05. When tolerated, elemental diet is as effective in the short term as prednisolone in newly and previously diagnosed Crohn's disease, and its benefit is independent of nutritional state. The subsequent relapse rate after elemental diet induced remission, however, is greater than after treatment with prednisolone.

Background: Endogenous vasodilators such as endothelially derived relaxant factor have been shown to modulate hypoxic pulmonary vasoconstriction. Sensory peptides such as substance P (SP) and calcitonin gene related peptide (CGRP) are also potent pulmonary vasodilators in both animals and humans. Their possible role in the modulation of the normal hypoxic pressor response has been examined in an isolated, ventilated, and blood perfused rat lung preparation., Methods: Animals (n = 7) were pretreated with 50 mg/kg capsaicin administered subcutaneously to deplete nerve endings of sensory neuropeptides. A control group (n = 7) received a subcutaneous dose of capsaicin vehicle. One week later the rats were killed and the rise in pulmonary artery pressure was measured during four successive periods of hypoxic ventilation (FIO2 0.03), and after four injections of angiotensin II (1.0 microgram)., Results: A 60% depletion of SP levels was measured in the sciatic nerves of animals treated with capsaicin. The hypoxic pressor response was not significantly altered in capsaicin treated animals compared with controls, except during the fourth hypoxic episode when it was augmented. The angiotensin II pressor response was the same in both groups during each of the injections., Conclusion: The sensory neuropeptide SP (and possibly CGRP) does not have a major role in modulating the pulmonary vascular response to hypoxia.

Adjuvant-induced arthritis results in chronic activation of the hypothalamo-pituitary-adrenal (HPA) axis. In the Piebald-Viral-Glaxo (PVG) rat, however, corticotropin-releasing factor (CRF) mRNA in the parvocellular paraventricular nucleus (pPVN) of the hypothalamus was reduced, and the normal corticosterone and CRF mRNA responses to acute stress were inhibited. The proenkephalin A mRNA response to stress in the pPVN was maintained, implying a specific inhibition of the CRF mRNA responses in this pathological situation. Adrenalectomy at day 0 (the time of adjuvant injection), day 13 (just before inflammation), or day 19 (submaximal inflammation) resulted in a marked increase in CRF mRNA compared with day 21 adrenal-intact arthritic animals. However, levels were below those of nonarthritic adrenalectomized rats, demonstrating that the inhibition of CRF mRNA associated with arthritis is not simply due to changes in glucocorticoid feedback. Proopiomelanocortin mRNA in the anterior pituitary was markedly increased in all adrenalectomized arthritic animals above the increase seen in sham-adrenalectomized day-21 arthritic rats. Adrenalectomy was always associated with an increase in the severity of the disease.

Mechanical stress causes remodelling of bone, a transformation of bone structure by physical forces through an unknown mechanism. Inflammation also affects bone structure, through altered use and the production of various inflammatory mediators. The peripheral nervous system may play both a sensory and an efferent role in the mechanical and inflammatory influences on bone structure. We studied the occurrence of substance P and calcitonin gene related peptide (CGRP) containing nerves in periosteal tissue, bone marrow, diaphysis and epiphysis of the ankle and knee joints of healthy and adjuvant arthritic rats. In arthritic animals, only ankle joints were affected by the inflammation. The periosteum was richly innervated both in healthy and arthritic animals. In arthritic rats few nerve fibers penetrated the woven, callous bone underlying the periosteum. Also bone marrow contained substance P and CGRP immunoreactive nerves in normal bone, whereas the hypercellular bone marrow of arthritic rats showed a decrease in the density of substance P and CGRP containing fibers. Epiphysis had a dense innervation compared to diaphysis. In contrast to large erosions, small peripheral erosions contained some CGRP immunoreactive fibers, perhaps as a sign of attempts of reactive repair. Our results suggest a local delivery system of potent peptide regulatory factors in bone, a system also affected by the pathophysiology of arthritis.

This prospective double blind randomised seven day crossover controlled clinical trial was carried out to determine whether enterally fed patients with moderately impaired gastrointestinal function require a predigested nitrogen (N) source compared with whole protein. Twelve malnourished patients with varying gastrointestinal abnormalities, who required enteral feeding, received 2.25 l of one of two isocaloric isonitrogenous enteral diets (1 kcal/ml, 4.8 g nitrogen/l) containing either predominantly medium chain peptides (tetra or higher peptides) or whole protein as the nitrogen source. Nitrogen absorption and balance were calculated from dietary intake and analysis of 24 hour total urinary and faecal nitrogen for the last five days of each study period. There was no significant difference in either stool weight (110 (SEM) (49) v 111 (32) g/d), nitrogen absorption (91 (2) v 89 (2)%) or nitrogen balance (+1.0 (1.3) v +0.6 (1.4) g nitrogen/d) between the peptide and whole protein nitrogen sources when all patients are considered. There was, however, evidence to suggest a nutritional advantage from administering an enteral diet whose nitrogen source comprises oligopeptides, rather than whole protein, to a subgroup of patients with small bowel disease.

Glycine has been regarded as a poor source of nitrogen for total parenteral nutrition. Two prospective randomised cross over controlled clinical trials were undertaken to compare the efficacy of high and low glycine containing amino acid solutions in parenterally fed malnourished hypoalbuminaemic patients with gastrointestinal disease. In the first study (n = 9), amino acid solutions in which glycine accounted for 23% and 4% of total nitrogen were compared. No statistically significant difference was found in urea nitrogen/total urinary nitrogen excretion (mean (SEM) 83.4 (1.4) v 81.6 (1.7)%, p = 0.31), nitrogen balance (-1.9 (2.4) v -0.6 (2.0) g/day, p = 0.31) or plasma protein concentrations and blood urea nitrogen. In the second extended study (n = 5), there was no significant difference in net whole body protein synthesis (+1.3 (4.7) v-0.2 (3.7) mg/kg/hour, p = 0.69) or fractional (0.403 (0.070) v 0.480 (0.41)%/hour, p = 0.68) and absolute albumin synthesis rates (6.0 (0.9) v 7.2 (0.06) mg/kg/hour, p = 0.22), on comparing solutions of 25% and 8% glycine nitrogen. In addition, a significantly higher proportion of total urinary nitrogen comprised urea when patients received the low glycine containing amino acid source (81.4 (2.5) v 83.8 (3.2)%, p = 0.04). It is concluded that there are no apparent short term nutritional or metabolic disadvantages to using amino acid solutions that contain up to 25% of nitrogen as glycine in total parenteral nutrition.

We have determined the time course of the neuroendocrine response of Piebald-Viral-Glaxo (PVG) rats during the development of mycobacterially induced adjuvant arthritis. Anterior pituitary POMC mRNA increased at the time of onset of mycobacterially induced arthritis, but, paradoxically, coincident with the first signs of arthritis there was a consistent fall in CRF mRNA in the hypothalamic paraventricular nucleus. Coincident with this fall in CRF message, there was a corresponding decrease in CRF-41 peptide release into the hypophysial portal blood (HPB). In contrast, however, vasopressin release into the HPB was increased. There was an increase in adrenal weight associated with the development of arthritis, reflecting chronic activation of the HPA axis, which was reflected by increased circulating corticosterone concentrations. The synthetic adjuvant CP20961, which has different antigenic determinants, also caused an increase in POMC mRNA in the anterior pituitary, a decrease in CRF mRNA in the hypothalamic paraventricular nucleus, and a decrease in CRF-41 peptide release into the HPB in PVG rats 28 days after the induction of the arthritis. The arginine vasopressin level was not significantly different from the control value. In Sprague-Dawley rats, mycobacterial adjuvant resulted in a similar increase in POMC mRNA in the anterior pituitary 28 days after injection of the adjuvant. In this strain of rat there was no corresponding change in CRF mRNA. While there are some strain differences in the degree of change in CRF mRNA, both strains showed a common paradox of a marked increase in adenohypophyseal POMC mRNA not associated with increased CRF mRNA or peptide release. In the PVG strain of rat, CRF actually appears to be inhibited. The mechanisms involved in this disparity are unclear.

The nervous system collects information from the outer world by specific senses and from the interior milieu by somatic senses. This information is processed and stored in memory and affects various bodily functions through the efferent arm of the nervous system. The efferent chemical neuropeptide message is transported intra-axonally to the site of action, which imparts site-specificity to the peripheral, paracrine neuropeptide effects. In the present study, immunohistochemistry using the immunoperoxidase method with nickel amplification was applied to visualize the topographical distribution of articular nerve fibres and nerve endings using the markers PGP 9.5 and synaptophysin, respectively. Furthermore, to get a comprehensive idea of the sensory innervation of the articular and para-articular tissue, antisera to calcitonin gene-related peptide (CGRP) and substance P were employed. Samples were collected after fixation by perfusion followed by immersion in fixative and decalcification by a special method, which also allows studies of the bone innervation. PGP 9.5- and synaptophysin-immunoreactive type IVa and IVb nerve fibres and endings were found in the synovial lining and sublining tissue and in the vascularized peripheral parts of the menisci. Furthermore, periosteum, bone marrow and the epiphyseal growth plates were also innervated, whereas innervation of the diaphyseal and metaphyseal bone was more sparse. PGP 9.5- and synaptophysin-immunoreactive nerves were also characterized by their CRGP, and to some extent, substance P content. Because of their distribution, the peripheral peptide-containing type IVa and IVb nerve fibres and nerve endings are in a position to participate in the pathogenesis of arthritis, including aspects of nociception, tissue remodelling and neurogenic inflammation.

The distribution of peptides thought to be involved in pain modulation--substance P, calcitonin gene-related peptide (CGRP), and enkephalin--were studied in the spinal cord and dorsal root ganglia of polyarthritic rats and in rats with one sciatic nerve sectioned prior to induction of arthritis. In arthritic rats there was a bilateral increase of CGRP- and substance P-immunoreactive fibers and appearance of enkephalin-immunoreactive cell bodies in the dorsal horn of the lumbar (L4) spinal cord when compared to controls. In the corresponding dorsal root ganglia there were significant increases of CGRP- (P less than 0.02) and substance P- (P less than 0.001) immunoreactive cell bodies compared to controls. In the ventral horn of the control rats CGRP-immunoreactive motoneurons were abundant but were significantly (P less than 0.001) reduced in the arthritic spinal cord. Less pronounced changes were seen in the contralateral L4 spinal cord of arthritic rats with unilateral sciatic nerve section. In the ipsilateral dorsal horn, however, CGRP- and substance P-immunoreactive fibers were markedly depleted, and no enkephalin cell bodies were present. Furthermore, a number of CGRP-immunoreactive motoneurons were observed. In the ipsilateral L4 ganglia CGRP- (P less than 0.02) and substance P- (P less than 0.02) immunoreactive cells were significantly decreased compared to the contralateral side. The data suggest that pain perception is linked to complex interactions between CGRP, substance P, and enkephalin in sensory pathways and an intact peripheral input. The loss of CGRP-immunoreactive motoneurons may reflect muscular dysfunction associated with the arthritic condition.

This case report describes the complication of peristomal abscess formation associated with the insertion of a percutaneous endoscopic gastrostomy (PEG). The formation of a peristomal anterior abdominal wall abscess in this patient was associated with the failure to give prophylactic antibiotics. The development of this potentially fatal complication may be avoided by strict observance of insertion protocols. This case was treated by removal of the gastrostomy tube after diagnosis which allowed drainage of the abscess. In similar cases of occult abscess formation, where symptoms are present but signs are absent, ultrasonography may be useful in diagnosis.

A proportion of patients requiring enteral nutrition is at increased risk of regurgitation or pulmonary aspiration of enteral diet as a result of gastric atony or paresis. The positioning of the distal end of an enteral feeding tube beyond the pylorus into duodenum or jejunum may reduce this risk. It has been postulated that by suitable lengthening of feeding tubes and by altering the distal end tip profile or by the addition of a weight, spontaneous passage of a tube through the pylorus after pernasal insertion may be achieved. In a recent controlled trial we were unable to demonstrate any advantage to a) modifying the tip profile or b) the addition of a 2.4 g weight. This prospective controlled clinical study examined the difference between an unweighted polyurethane tube which had performed optimally in the previous study and a new 7 g weighted tube similar in all other respects. In both cases less than 50% of tubes had passed spontaneously through the pylorus when assessed at 24 h, with no significant difference in performance (p = 0.38). When comparing overall length of time that each tube remained in situ, there was similarly no significant difference between the 7 g weighted and unweighted tubes (p = 0.277). We conclude that the addition of a 7 g weight to a suitably lengthened enteral feeding tube confers no advantage on either incidence of spontaneous transpyloric passage or in prolonging tube usage. If post-pyloric feeding is indicated for a patient, positioning by either fluoroscopic or endoscopic techniques should be undertaken.

A series of studies was performed to test the efficacy and safety of a parenteral lipid emulsion, Lipofundin S, when given as part of a complete nutritive mixture from the three-liter bag total parenteral nutrition (TPN) delivery system. In vitro stability studies with mixtures corresponding to high and low nutritional intakes showed the fat emulsion to be stable during refrigerated storage for at least 6 days. The clinical use of Lipofundin S in 3-liter TPN bags was studied in 39 consecutive patients requiring TPN, and there were no untoward side-effects. Nitrogen balance was maintained in patients with pancreatitis, those recovering postoperatively, and those with miscellaneous conditions. However, patients with multiple trauma remained in negative balance. The ability of sera, from patients on TPN to agglutinate Lipofundin S was compared to that from healthy controls, and acutely ill patients not on TPN. Patients on TPN showed a higher degree of in vitro creaming than acutely ill controls, and this may have been related to the severity of the underlying illness. These studies suggest that this parenteral lipid emulsion can be safely administered to patients requiring TPN when given from the 3-liter bag delivery system.

Disappointed with the overall performance of weighted and unweighted nasogastric feeding tubes, a design programme was initiated which resulted in the development of two new nasogastric tubes, one weighted and one unweighted. The tubes were manufactured with polyurethane rather than polyvinylchloride (PVC) which permitted an increase in diameter of the internal lumen which in turn was coated with water activated lubricant to ease removal of the introducer wire. A specially modelled outflow port was incorporated into the tips of both tubes. The performance of the two new polyurethane nasogastric feeding tubes was assessed under controlled trial condition using as a reference a widely used PVC unweighted open ended tube. While intubation times were similar in patients without concurrent endotracheal intubation, it took a significantly shorter time to intubate patients with concurrent endotracheal intubation with the new weighted tube. Following tube intubation, it was possible to aspirate gastric contents significantly more often through the new polyurethane tubes (p < 0.001) than through the PVC tube, and the unweighted polyurethane tube stayed in situ longer (p < 0.05) than the PVC tube. The newly designed polyurethane nasogastric feeding tubes are the first tubes that have been shown to have advantages over the simpler type of open ended, unweighted PVC nasogastric feeding tubes.