[What is the management for foot ulcers in diabetic patients?]. / Que faire devant un ulcère du pied chez un patient diabétique?

The "diabetic foot" covers the spectrum of neurological, arterial and infectious foot problems that occur as a consequence of diabetes. The wounds, often due to minor injuries, may lead to amputations if not quickly treated. The treatment consists of efficiently alleviating mechanical pressure from the wound (i.e. prevention of repeated trauma by walking on the ulcer) on the one hand, and using adequate local care on the other. In addition, the patient's vascular status needs to be assessed and corrected. If present, infections must be quickly and aggressively treated. The infection may be either superficial or deep and the presence of bone contact at clinical examination is suggestive of osteitis. Optimal care is provided in diabetic foot centers by multidisciplinary teams. These teams include a diabetologist, dermatologist, vascular surgeon, infectiologist, radiologist, podologist, shoemaker and specialized nurses. The main aim is to reduce the number of amputations. The best treatment, however, aims at prevention of foot wounds. It requires knowledge of the physiopathological mechanisms of diabetic foot, the screening for feet at risk, and the education of the patient, family and health care providers.

11C-methionine PET for the diagnosis and management of recurrent pituitary adenomas.

PURPOSE: The detection of recurrent pituitary adenoma by magnetic resonance imaging (MRI) is rendered uncertain by the tissue remodelling that follows surgery or radiotherapy. We aimed to evaluate the contribution of PET with 11C-methionine (MET-PET) in the detection and management of recurrent pituitary adenoma. METHODS: Thirty-three patients with pituitary adenoma were evaluated postoperatively by MET-PET, either because of biological evidence of active residual tumour or because of MRI demonstration of non-functional adenoma growth. We studied 24 secreting adenomas and nine non-functional adenomas. RESULTS: In 30 patients, MET-PET detected abnormally hypermetabolic tissue. In 14 out of these, MRI did not differentiate between residual tumour and scar formation. In nine of these 14 cases, major therapeutic decisions were undertaken (radiosurgery and surgery). In another group of 16 patients, both MET-PET and MRI detected abnormal tissue. In one case, neither MRI nor MET-PET detected adenomatous tissue. Finally, abnormal tissue was detected in two patients on MRI solely. In these two cases, failure of MET-PET to reveal the adenoma was attributable to concomitant inhibitory therapy. The sensitivity of MET-PET and MRI varied as a function of the tumour type: all non-functional adenomas were localised by both modalities, while MET-PET detected all adrenocorticotropic hormone-secreting adenomas whereas MRI depicted only one of these eight lesions. Fifteen out of 17 patients treated by radiosurgery showed clinical improvement after treatment. CONCLUSION: We suggest that MET-PET is a sensitive technique complementary to MRI for the detection of residual or recurrent pituitary adenomas. It should gain a place in the efficient management of these tumours.

[Subclinical hypothyroidism]. / L'hypothyroïdie subclinique.

Subclinical hypothyroidism is defined as normal serum free thyroxine and tri-iodothyronine concentrations and a slightly eleveted serum thyrotropin (TSH) concentration. Only laboratory results can detect this disorder. The causes of this disease are the same as those of overt hypothyroidism. Most patients with subclinical hypothyroidism should be treated with thyroxine aiming to reduce the patient's serum TSH concentration to normal. Treatment will prevent progression to overt hypothyroidism and in some cases ameliorate non specific symptoms and lipid profile.

Two new peptides to improve post-operative gastric ileus in dog.

Peptides can influence gastrointestinal motility, and from data obtained earlier in rats, we hypothesized that MTL-RP/Ghrelin, as well as CGRP receptor antagonist 8-37, could improve gastric post-operative ileus in dog. Dogs submitted to laparotomy were perfused with or saline or CGRP 8-37 or MTL-RP/Ghrelin on days 1-4 post-operatively while gastric emptying was estimated by measuring the postprandial increase in plasma acetaminophen ingested with a meal. As expected, in saline-treated animals the gastric emptying function was impaired post-operatively. The total amount of acetaminophen emptied (AUC over 150 min) on post-operative days 1-4 reached respectively 31+/-5%, 65+/-8%, 60+/-8% and 62+/-8% of the normal emptying capacity. CGRP antagonist increased the total emptying of acetaminophen to 52+/-5% on day 1, 95+/-2% on day 2 and 103+/-3% (P<0.05) on day 3. The delayed emptying of acetaminophen seen post-operatively in saline-treated animals could be completely reversed by MTL-RP/Ghrelin (P<0.01) whether it was given at 100 microg/kg on day 2 (102+/-7% of the normal emptying capacity), 4 microg/kg on day 3 (106+/-7%) or 20 microg/kg on day 4 (132+/-8%). As found earlier in rodents, CGRP receptor antagonist 8-37 as well as MTL-RP/Ghrelin are potent prokinetics to improve post-operative gastric ileus in dog.

Therapeutic potential of the intestinotropic hormone, glucagon-like peptide-2.

Glucagon-like peptide-2 (GLP-2) is a newly discovered growth factor that has been demonstrated to enhance intestinal growth and function in normal rodents and to prevent damage and facilitate intestinal repair in various animal models of intestinal insufficiency. A recent study has demonstrated that GLP-2 also acts as an intestinotropin in humans with short-bowel syndrome. The high degree of specificity of GLP-2 for induction of intestinal growth, without affecting growth of other peripheral tissues, is determined by the highly localized expression of the GLP-2 receptor in the intestinal epithelium. In this article, we review the regulation of GLP-2 in physiology, from synthesis to metabolism, with a particular emphasis on potential targets in this pathway for therapeutic manipulation of GLP-2 actions. We also discuss the various animal models of intestinal insufficiency that have been used to demonstrate the therapeutic potential of this intestinotropic hormone, including short bowel, intestinal atrophy, enteritis and colitis. The results of these studies indicate that GLP-2 is a promising therapeutic agent for the treatment of various forms of intestinal insufficiency in humans.

Digestive motor effects and vascular actions of CGRP in dog are expressed by different receptor subtypes.

Calcitonin gene-related peptide (CGRP) is a 37 AA peptide localized in blood vessels and nerves of the GI tract. Activation of CGRP receptors (subtypes 1 or 2) usually induces vasodilation and/or muscle relaxation, but its effects in dog and on gastroduodenal motility are still unclear. This study looked for the effect of CGRP and the antagonist CGRP8-37, specific for CGRP type 1 receptor, 1) on GI motility (interdigestive and postprandial), and 2) on hemodynamy, in conscious dogs. During the interdigestive period, the infusion of CGRP1-37 (200 pmol/kg/h) or CGRP8-37 (2000 pmol/kg/h) did not modify the duration of the migrating motor complex nor the release nor the motor action of plasma motilin. The gastric emptying of a solid meal (15 g meat/kg) was reduced by the administration of CGRP1-37 (AUC: 2196 +/- 288.6 versus 3618 +/- 288.4 with saline or T12: 78 +/- 7.3 versus 50 +/- 4.3 min; P < 0.01) and this effect was reversed by the antagonist CGRP8-37. CGRP1-37 significantly (P < 0. 01) diminished arterial pressures (118 +/- 1.6/64 +/- 1.4 vs. 125 +/- 1.4/75 +/- 1.2 mmHg with saline) and accelerated the basal cardiac rhythm (110 +/- 1.4 versus 83 +/- 1.6 beats/min). However, CGRP8-37 failed to block the cardiovascular effects of CGRP1-37. In dog, CGRP could influence digestive motility by slowing the gastric emptying of a meal through an action on CGRP-1 receptors. Hemodynamic effects of CGRP were not blocked by CGRP8-37 and seem therefore mediated by CGRP-2 receptor subtype.

Characterization of lung surfactant: factors promoting formation of artifactual lipid-protein complexes.

Because uncertainty exists as to whether dipalmitoyl phosphatidylcholine, the major component of lung surfactant, is part of a lipoprotein molecule, a study was designed to investigate the relationships between the phospholipids and proteins of rabbit lung washings obtained by lavage with aqueous solutions. Surface-active sediments contained phospholipid and protein in ratios directly dependent upon the ratios in the washings from which they were obtained. Comparison of negatively stained lung washings and sediments revealed that sedimentation caused extensive aggregation of surfactant "liposomes". Analytical ultracentrifugation revealed that both cell-free washings from lungs and suspension of pure phosphatidylcholine contained components with flotation rates ranging from 25 to 400. Density gradient centrifugation of washings, without prior sedimentation, resulted in the appearance of a phospholipid band associated with only a small amount of protein. The density of the band varied depending upon temperature. No qualitative differences in the protein compositions of the phospholipid band and other gradient fractions were found by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Albumin, IgG, IgM, and several nonplasma proteins were present. These results indicate that little, if any, protein is specifically attached to the phospholipids of lung surfactant; rather, the lipid-protein complexes of lung washings are the result of a nonspecific association caused by removal of water-soluble surfactant from the lung and promoted by sedimentation.