Does the Length of the Common Channel as Part of the Total Alimentary Tract Matter? One Year Results from the Multicenter Dutch Common Channel Trial (DUCATI) Comparing Standard Versus Distal Roux-en-Y Gastric Bypass with Similar Biliopancreatic Bowel Limb Lengths.

PURPOSE: Although the laparoscopic Roux-en-Y Gastric Bypass (LRYGB) is the gold-standard bariatric procedure, it remains uncertain what the optimal bowel limb lengths are to accomplish maximal weight loss while minimizing nutritional deficiencies and related gastro-intestinal complaints. The aim of this randomized controlled multicenter trial is to investigate the effect of significant lengthening of the length of the Roux limb (RL) at the cost of the length of the common channel (CC) while keeping the biliopancreatic limb (BPL) lengths the same on both study arms. METHODS: Four hundred forty-four patients were randomized to receive either a Very Long Roux Limb LRYGB (VLRL-LRYGB) (variable RL length, BPL 60 cm, and CC 100 cm) or a Standard LRYGB (S-LRYGB) (RL 150 cm, BPL 60 cm, and a variable CC length). Results at 1-year follow-up for weight loss, effect on obesity-related comorbid conditions, complications, re-operation rate, malnutrition rate, and re-admission rate were investigated. RESULTS: Weight loss at 1-year showed no significant differences for %EWL (84.3% versus 85.3%, p = 0.72) and %TWL (34.2% versus 33.6%, p = 0.359) comparing VLRL-LRYGB versus S-LRYGB. Malabsorption requiring surgical bowel length adjustment was observed in 1.4% in VLRL-LRYGB group versus 0.9% in S-LRYGB group (p = 0.316). CONCLUSION: Significant lengthening of the RL at the cost of the common channel seems to have no effect on the weight loss at 1-year follow-up, which supports the theory that absorption of nutrients also occurs in the RL. Nevertheless, long-term results of the VLRL-LRYGB have to be awaited to draw final conclusions as part of the discussion towards optimal limb length in LRYGB surgery.

The Prognostic Value of the Dutch Sweet Eating Questionnaire on Weight Loss After Metabolic Surgery: a Randomized Controlled Trial.

BACKGROUND: Laparoscopic Roux-en-Y gastric bypass (LRYGB) and laparoscopic sleeve gastrectomy (LSG) have shown different weight loss results. These differences might be partly due to dumping after LRYGB, forcing sweet eaters to switch to a healthy diet. The Dutch Sweet Eating Questionnaire (DSEQ) is validated to measure sweet eating. This study aims to investigate if sweet eating measured with the DSEQ influences weight loss. METHODS: In this multicenter randomized controlled trial, patients were included between 2013 and 2017 in two Dutch high-volume hospitals, and randomized with a 1:1 ratio between LRYGB and LSG. Primary outcome measure was weight loss. Secondary outcome measure was sweet eating behavior, measured with the DSEQ. Data was collected at baseline, 1 year and 2 years postoperatively. RESULTS: Data was analyzed of 623 patients who underwent LRYGB (n = 308; 49.4%) or LSG (n = 315; 50.6%). Follow-up rates at 2 years postoperative were 67.1% for weight and 35.3% for DSEQ. At 2 years postoperative, mean BMI was significantly higher after LSG than LRYGB (respectively 30.88 versus 28.87 kg/m2, p < 0.001), and the percentage of sweet eaters was significantly higher after LSG than LRYGB (respectively 8.6% versus 2.6%, p = 0.049). None of the preoperative sweet eaters were sweet eaters 2 years after LRYGB (0.0%), versus 11.8% 2 years after LSG. No correlation was found between postoperative sweet eating behavior and %EBMIL. CONCLUSION: No significant correlation was found between preoperative or postoperative sweet eating measured with the DSEQ and weight loss. The decision-making for the procedure type is more complex than weight loss and dietary habits, and should also involve quality of life and presence of comorbidities. These factors should be addressed in future research along with longer term results. TRIAL REGISTRATION: Dutch Trial Register NTR-4741.

Effects of standard v. very long Roux limb Roux-en-Y gastric bypass on nutrient status: a 1-year follow-up report from the Dutch Common Channel Trial (DUCATI) Study.

Laparoscopic Roux-en-Y gastric bypass (RYGB) is considered the 'gold standard' for surgical treatment of morbid obesity. It is hypothesised that reducing the length of the common limb positively affects the magnitude and preservation of weight loss but may also impose a risk of malnutrition. The aim of this study was to compare patients' nutrient and vitamin deficiencies in standard RYGB with a very long Roux limb RYGB (VLRL-RYGB). This study was part of the multicentre randomised controlled trial (Dutch Common Channel Trial), including 444 patients undergoing an RYGB or a VLRL-RYGB. Laboratory results, use of multivitamin supplements and reoperations were collected at baseline and 1 year postoperative. Primary outcome measure was nutrient deficiency after 1 year postoperative. Secondary outcome measure was the reoperation rate due to malabsorption. In total, 227 patients underwent RYGB and 196 patients underwent VLRL-RYGB. Most common deficiencies at 1 year postoperative were ferritin (17·2-18·2 %), Fe (23·4-35·6 %), K (7·4-15·2 %), vitamin B12 (9·0-9·9 %) and vitamin D (22·7-34·5 %). Patients undergoing VLRL-RYGB had slightly but significantly lower levels of Ca, Fe and vitamin D compared with those undergoing RYGB at 1 year postoperative, but significantly higher levels of folic acid and Na. Reoperation rates due to malabsorption were not significantly different between RYGB (2/227, 0·9 %) and VLRL-RYGB (7/196, 3·6 %) (P = 0·088). We concluded that patients undergoing VLRL-RYGB had significantly lower levels of Ca, Fe and vitamin D compared with those undergoing RYGB at 1 year postoperative, but higher levels of folic acid and Na. Reoperation rates did not differ. Close monitoring on nutrient deficiencies should be performed in patients undergoing VLRL-RYGB.

The Influence of Surgical Experience on Postoperative Recovery in Fast-Track Bariatric Surgery.

INTRODUCTION: Short duration of surgery is an important aspect in fast-track protocols. Peroperative training of surgical residents could influence the duration of surgery, possibly affecting patient outcome. This study evaluates the influence of the operator's level of experience on patient outcome in fast-track bariatric surgery. METHODS: Data was analyzed of all patients who underwent a primary laparoscopic Roux-en-Y gastric bypass (LRYGB) or laparoscopic sleeve gastrectomy (LSG) between January 2004 and July 2018. Residents were trained according to a stepwise training program. For each operator, learning curves of both procedures were created by dividing the procedures in time-subsequent groups (TSGs). Data was also analyzed by comparing "beginners" with "experienced operators," with a cut-off point at 100 procedures. Primary outcome measure was duration of surgery. Secondary outcome measures were length of hospital stay (LOS), complications, and readmission rate within 30 days postoperatively. RESULTS: There were 4901 primary procedures (53.1% LSG) performed by seven surgeons or surgical residents. We found no difference between beginning and experienced operators in complications or readmissions rates. The experience of the operator did not influence LOS (p = 0.201). Comparing each new operator with previous operator(s), the starting point in terms of duration of surgery was shorter, and the learning curve was steeper. The duration of surgery was significantly longer for supervised beginning operators as compared with experienced operators. CONCLUSION: Within the stepwise training program for residents, there is a slight increase in duration of surgery in the beginning of the learning curve, without affecting the patient outcome.

A Single-Center Comparison of Extended and Restricted THROMBOPROPHYLAXIS with LMWH after Metabolic Surgery.

INTRODUCTION: Morbid obesity is an important risk factor for developing a venous thromboembolic events (VTE) after surgery. Fast-track protocols in metabolic surgery can lower the risk of VTE in the postoperative period by reducing the immobilization period. Administration of thromboprophylaxis can be a burden for patients. This study aims to compare extended to restricted thromboprophylaxis with low molecular weight heparin (LMWH) for patients undergoing metabolic surgery. METHODS: In this single center retrospective cohort study, data was collected from patients undergoing a primary Roux-en-Y gastric bypass (RYGB) or sleeve gastrectomy (SG) between 2014 and 2018. Patients operated in 2014-2017 received thromboprophylaxis for two weeks. In 2018, patients only received thromboprophylaxis during hospital admission. Patients already using anticoagulants were analyzed as a separate subgroup. The primary outcome measure was the rate of clinically significant VTEs within three months. Secondary outcome measures were postoperative hemorrhage and reoperations for hemorrhage. RESULTS: 3666 Patients underwent a primary RYGB or SG following the fast-track protocol. In total, two patients in the 2014-2017 cohort were diagnosed with VTE versus zero patients in the 2018 cohort. In the historic group, 34/2599 (1.3%) hemorrhages occurred and in the recent cohort 8/720 (1.1%). Postoperative hemorrhage rates did not differ between the two cohorts (multivariable analysis, p = 0.475). In the subgroup of patients using anticoagulants, 21/347(6.1%) patients developed a postoperative hemorrhage. Anticoagulant use was a significant predictor of postoperative hemorrhage (p < 0.001). CONCLUSION: Despite the restricted use of thromboprophylaxis administration since 2018, the rate of VTEs did not increase. This may be explained by quick mobilization and hospital discharge, as encouraged by the fast-track protocol. There was no significant difference in postoperative hemorrhage rates by thromboprophylaxis protocol. Short term use of thromboprophylaxis in metabolic surgery is safe in patients at low risk of VTE.

How the concept of biochemical response influenced the management of primary biliary cholangitis over time.

BACKGROUND: Criteria assessing biochemical response to ursodeoxycholic acid (UDCA) are established risk stratification tools in primary biliary cholangitis (PBC). We aimed to evaluate to what extent liver tests influenced patient management during a three decade period, and whether this changed over time. METHODS: 851 Dutch PBC patients diagnosed between 1988 and 2012 were reviewed to assess patient management in relation to liver test results during UDCA treatment. To do so, biochemical response at one year was analysed retrospectively according to Paris-1 criteria. RESULTS: Response was assessable for 687/851 (81%) patients; 157/687 non-responders. During a follow-up of 8.8 years (IQR 4.8-13.9), 141 died and 30 underwent liver transplantation. Transplant-free survival of non-responders (60%) was significantly worse compared with responders (87%) (p < 0.0001). Management was modified in 46/157 (29%) non-responders. The most frequent change observed, noted in 26/46 patients, was an increase in UDCA dosage. Subsequently, 9/26 (35%) non-responders became responders within the next two years. Steroid treatment was started in one patient; 19 patients were referred to a tertiary centre. No trend towards more frequent changes in management over time was observed (p = 0.10). CONCLUSION: Changes in medical management occurred in a minority of non-responders. This can largely be explained by the lack of accepted response criteria and of established second-line treatments for PBC. Nevertheless, the observation that response-guided management did not increase over time suggests that awareness of the concept of biochemical response requires further attention,particularly since new treatment options for PBC will soon become available.

[Management of high blood pressure in patients with chronic kidney disease : Summary of recent guidelines]. / Prise en charge de l'hypertension artérielle chez le patient souffrant de maladie rénale chronique, que disent les guidelines en 2016 ?

Chronic kidney disease and high blood pressure are two common diseases that mutually maintain during their evolution. In the advanced stages of chronic kidney disease, most pat ients are hypertensive and show signs of vascular disease (coronary artery disease, cerebrovascular or peripheral). Almost one third of the patients with advanced chronic kidney disease exhibit resistant hypertension that requires complex therapeutic management. In chronic kidney disease, antihypertensive treatment is conditioned by comorbidities, but also by proteinuria, which is an independent cardiovascular risk factor in addition to the rate of glomerular filtration rate. The treatment of high blood pressure is a cornerstone of the management of the chronic kidney disease. It limits the risk of cardiovascular events (eg. myocardial infarction, stroke), but also slows the progression of chronic kidney disease. Various recommendations have been recently published on the subject in order to offer assistance to the therapeutic management of hypertension in the patient suffering from chronic kidney disease. The purpose of this article is to highlight these main key elements.

La maladie rénale chronique et l'hypertension artérielle sont 2 pathologies fréquentes qui s'entretiennent mutuellement au cours de leur évolution. Lors des stades avancés de la maladie rénale chronique, une très grande majorité des patients sont hypertendus, mais présentent aussi des signes d'artériopathie (maladies artérielles coronariennes, cérébrales ou périphériques). Pratiquement un tiers des patients souffrant de maladie rénale chronique avancée souffrent d'hypertension artérielle résistante qui nécessite une prise en charge thérapeutique complexe. En cas de maladie rénale chronique, le traitement ant ihypertenseur est condit ionné par les comorbidités, mais aussi par la protéinurie, facteur de risque cardiovasculaire indépendant du débit de filtration glomérulaire. Le traitement de l 'hyper tension artérielle est une pierre angulaire de la prise en charge du patient atteint de maladie rénale chronique. Il permet de limiter le risque d'événement vasculaire (par ex. infarctus du myocarde, accident vasculaire cérébral), mais aussi de ralentir la progression de la maladie rénale chronique. Différentes recommandations ont été publiées récemment sur le sujet afin de proposer une aide à la prise en charge thérapeutique de l'hypertension artérielle chez le patient atteint de maladie rénale chronique. L'objectif du présent article est d'en souligner les principaux éléments-clés.

[Management of severe arterial hypertension]. / Le traitement d'urgence de I'hypertension artérielle sévère.

Severe arterial hypertension is defined as a systolic blood pressure (BP) ≥180 mmHg and/or a diastolic BP ≥ 110 mmHg. Initial assessment is to identify acute, ongoing, target-organ damage such as pulmonary edema, aortic dissection, ... (hypertensive emergency). If so, the patient requires urgent and specific management in a hospital setting. More commonly, however, BP in the severe range is relatively asymptomatic and not associated with end-organ damage (hypertensive urgency). Management can usually be carried out in the ambulatory setting. Severe hypertension should first be confirmed after a period of rest in a quiet room. If BP remains in the severe range, an antihypertensive drug can be initiated. Otherwise, the patient should be referred for further evaluation within a few days ; however, an antihypertensive treatment could be started immediately if there is concern that urgent outpatient follow-up cannot be ensured or if the patient is at high cardiovascular risk. The choice of the first drug should be tailored according to associated conditions and possible contraindications. Some guidelines recommend starting therapy with an antihypertensive combination of two drugs. In all cases, rapid and excessive reduction in BP, which could compromise organ perfusion, must be avoided, especially in elderly patients. In the short-term (days), BP should be progressively lowered to < 160/100 mmHg. In the long term, a BP < 140/90 mmHg should be obtained.

The intra-gastric balloon for pre-operative weight loss in bariatric surgery: is it worthwhile?

BACKGROUND: Super-obese patients in NHS Lothian during 2009-2010 were offered the intragastric balloon to assist with weight loss prior to definitive bariatric surgery along with participation in a structured weight management programme. Those who declined balloon placement continued to receive weight management alone (WM). The aim of this study was to compare the effectiveness of the structured weight management programme with and without the addition of the intragastric balloon. METHODS: Patients referred to the NHS Lothian Bariatric Service in 2009 with BMI > 55 kg/m(2) or weight > 200 kg and assessed as otherwise eligible for bariatric surgery were offered structured weight management with or without placement of an intragastric balloon with the aim of achieving a target of 10 % excess weight loss (EWL) over 6 months. RESULTS: Twenty-eight patients were recruited. Fifteen opted for balloon placement and 13 declined. Three patients in the balloon group required early balloon removal due to intolerance and three dropped out of the WM group through non-attendance. Of those remaining, two in the balloon group and three in the WM group failed to achieve the 10 % EWL target. Overall, median %EWL was 17.1 % for the balloon group and 16.1 % for the WM group (p = 0.295, Mann-Witney U-test). CONCLUSIONS: The additional use of intragastric balloon conferred no benefit over structured weight management alone in achieving pre-operative weight loss in a super-obese patient population. In the context of limited resources within NHS Lothian, the continued use of intragastric balloon in this way cannot be justified.

[Antihypertensive drugs in 2010: old and new agents]. / Antihypertenseurs en 2010: les anciens et les modernes.

High blood pressure is a major cardiovascular risk factor and its treatment reduces the risk. Five classes of antihypertensive drugs are suitable for the treatment of hypertension either as monotherapy or in some combinations with each other: thiazide and thiazide-like diuretics, beta-blockers, calcium antagonists, angiotensin-converting enzyme inhibitors and angiotensin receptor antagonists. The benefits of antihypertensive treatment are mainly due to lowering of blood pressure and are largely independent of the drug employed. For a given reduction in blood pressure, there is no evidence that "new" antihypertensive agents are superior to "old" agents. In the majority of patients, two or more antihypertensive drugs are required to achieve target blood pressure levels. Preferred drug combinations are diuretics with any of other antihypertensive drugs (with the exception of the combination with beta-blockers in patients at risk of diabetes mellitus), and angiotensin-converting enzyme inhibitors with calcium antagonists. On the other hand, the combination of an angiotensin-converting enzyme inhibitor with an angiotensin receptor antagonist should not be employed because of a high incidence of serious adverse renal outcomes. Recently, the first orally active direct renin inhibitor, aliskiren, has been launched for clinical use. The results of ongoing long-term outcome studies will determine the place of aliskiren in the treatment of hypertension.

[Arterial hypertension in pregnancy]. / Hypertension artérielle et grossesse.

Hypertensive disorders are the most common medical disorders of pregnancy and are associated with adverse maternal and perinatal outcomes. When considering pregnancy, women with pre-existing chronic hypertension should be screened for target organ damage, especially renal dysfunction. Since blood pressure usually decreases until midpregnancy and returns to, or exceeds, prepregnancy values in the third trimester, antihypertensive treatment can sometimes be withdrawn in low-risk women, and reintroduced if needed. Recommended antihypertensive drugs are labetalol, methyldopa and nifedipine. Angiotensin converting enzyme inhibitors, angiotensin II receptor antagonists and atenolol must be avoided. The occurrence of superimposed preeclampsia should be detected by appropriate clinical and laboratory evaluation. Preeclampsia is a multisystem maternal and fetal syndrome. The risk of preeclampsia is slightly reduced by low-dose aspirin and by calcium supplementation in women with low dietary calcium intake. For early-onset preeclampsia, expectant management improves perinatal outcomes, but requires close maternal and fetal surveillance. For acute management of severe hypertension, intravenous labetalol and oral nifedipine are recommended. Delivery is indicated in the presence of signs of maternal or fetal distress. Magnesium sulfate is indicated for the prophylaxis and the treatment of eclampsia. Most antihypertensive agents are compatible with breast feeding. Early-onset or severe preeclampsia increase the risk of remote chronic hypertension and cardiovascular disease.

Glycaemic and satiating properties of potato products.

OBJECTIVE: To investigate glycaemic and satiating properties of potato products in healthy subjects using energy-equivalent or carbohydrate-equivalent test meals, respectively. SUBJECTS AND SETTING: Thirteen healthy subjects volunteered for the first study, and 14 for the second. The tests were performed at Applied Nutrition and Food Chemistry, Lund University, Sweden. EXPERIMENTAL DESIGN AND TEST MEALS: All meals were served as breakfast in random order after an overnight fast. Study 1 included four energy-equivalent (1000 kJ) meals of boiled potatoes, french fries, or mashed potatoes; the latter varying in portion size by use of different amounts of water. The available carbohydrate content varied between 32.5 and 50.3 g/portion. Capillary blood samples were collected during 240 min for analysis of glucose, and satiety was measured with a subjective rating scale. Study 2 included four carbohydrate-equivalent meals (50 g available carbohydrates) of french fries, boiled potatoes served with and without addition of oil, and white wheat bread (reference). The energy content varied between 963 and 1534 kJ/portion. Capillary blood samples were collected during 180 min for analysis of glucose, and satiety was measured using a subjective rating scale. RESULTS: Study 1: boiled potatoes induced higher subjective satiety than french fries when compared on an energy-equivalent basis. The french fries elicited the lowest early glycaemic response and was less satiating in the early postprandial phase (area under the curve (AUC) 0-45 min). No differences were found in glycaemic or satiety response between boiled or mashed potatoes. Study 2: french fries resulted in a significantly lower glycaemic response (glycaemic index (GI)=77) than boiled potatoes either with or without addition of oil (GI=131 and 111, respectively). No differences were found in subjective satiety response between the products served on carbohydrate equivalence. CONCLUSIONS: Boiled potatoes were more satiating than french fries on an energy-equivalent basis, the effect being most prominent in the early postprandial phase, whereas no difference in satiety could be seen on a carbohydrate-equivalent basis. The lowered GI for french fries, showing a typical prolonged low-GI profile, could not be explained by the fat content per se.

[Control of hypertension in nursing homes]. / Contrôle de i'hypertension en maison de repos et maison de repos et de soins.

In a cross sectional study we determined prevalence of hypertension among institutionalized old subjects. Prevalence of hypertension was 69%. Among detected hypertensive patients, 76% received an antihypertensive drug treatment. 61% of the declared hypertensive patients and 80% of the treated hypertensive patients had their blood pressure controlled. The general practitioners should better detect and treat this common geriatric problem associated with a high comorbidity.

[Cardiovascular diseases: which prevention for which patient?]. / Les maladies cardiovasculaires: quelle prévention pour quel patient?

Several cardiovascular risk factors have been identified, which can be influenced by lifestyle modifications and medication. Many cardiovascular events could be prevented using appropriate preventive measures. The distinction between primary and secondary prevention is gradually disappearing. Lifestyle modifications must be recommended in all patients, and, depending on the individual's risk profile, drug interventions can also be used to improve cardiovascular prognosis, including antihypertensive drugs, lipid-lowering therapies, hypoglycaemic drugs, and antithrombotic agents. This article summarises the most recent guidelines on the prevention of common cardiovascular diseases: coronary artery disease, stroke, and peripheral artery disease.

Timing of re-transfusion drain removal following total knee replacement.

INTRODUCTION: The use of postoperative drains following total knee replacement (TKR) has recently been modified by the use of re-transfusion drains. The aim of our study was to investigate the optimal time for removal of re-transfusion drains following TKR. PATIENTS AND METHODS: The medical records of 66 patients who had a TKR performed between October 2003 and October 2004 were reviewed; blood drained before 6 h and the total volume of blood drained was recorded. RESULTS: A total of 56 patients had complete records of postoperative drainage. The mean volume of blood collected in the drain in the first 6 h was 442 ml. The mean total volume of blood in the drain was 595 ml. Therefore, of the blood drained, 78% was available for transfusion. CONCLUSION: Re-transfusion drains should be removed after 6 h, when no further re-transfusion is permissible.

Vinegar dressing and cold storage of potatoes lowers postprandial glycaemic and insulinaemic responses in healthy subjects.

OBJECTIVE: To investigate the effects of cold storage and vinegar addition on glycaemic and insulinaemic responses to a potato meal in healthy subjects. SUBJECTS AND SETTING: A total of 13 healthy subjects volunteered for the study, and the tests were performed at Applied Nutrition and Food Chemistry, Lund University, Sweden. Experimental design and test meals:The study included four meals; freshly boiled potatoes, boiled and cold stored potatoes (8 degrees C, 24 h), boiled and cold stored potatoes (8 degrees C, 24 h) with addition of vinaigrette sauce (8 g olive oil and 28 g white vinegar (6% acetic acid)) and white wheat bread as reference. All meals contained 50 g available carbohydrates and were served as a breakfast in random order after an overnight fast. Capillary blood samples were collected at time intervals during 120 min for analysis of blood glucose and serum insulin. Glycaemic (GI) and insulinaemic indices (II) were calculated from the incremental areas using white bread as reference. RESULTS: Cold storage of boiled potatoes increased resistant starch (RS) content significantly from 3.3 to 5.2% (starch basis). GI and II of cold potatoes added with vinegar (GI/II=96/128) were significantly reduced by 43 and 31%, respectively, compared with GI/II of freshly boiled potatoes (168/185). Furthermore, cold storage per se lowered II with 28% compared with the corresponding value for freshly boiled potatoes. CONCLUSION: Cold storage of boiled potatoes generated appreciable amounts of RS. Cold storage and addition of vinegar reduced acute glycaemia and insulinaemia in healthy subjects after a potato meal. The results show that the high glycaemic and insulinaemic features commonly associated with potato meals can be reduced by use of vinegar dressing and/or by serving cold potato products.

Effects of low-dose dopamine on ventilation in patients with chronic obstructive pulmonary disease.

BACKGROUND: Dopamine plays an important role in the regulation of respiration and low-dose dopamine infusion is associated with a decreased respiratory drive response to hypoxia in animals and humans. The effects of dopamine on ventilation in patients with chronic obstructive pulmonary disease (COPD) is unknown. We tested the hypothesis that dopamine inhibits ventilation in patients with COPD. MATERIALS AND METHODS: In a double-blinded, cross-over, placebo-controlled, randomized study we studied nine patients with decompensated COPD, ventilated in the pressure support mode in the intensive care unit (ICU) and five ambulatory patients with stable COPD. All patients received 5 micro g kg(-1) min(-1) of dopamine or an equivalent volume of 5% glucose solution. RESULTS: In the mechanically ventilated COPD patients, there was no difference in the effects of dopamine compared with placebo on blood pressure, heart rate, minute ventilation (-0.5 +/- 1.1 vs. -0.2 +/- 0.9 L min(-1), P = 0.46, respectively), respiratory rate (-0.4 +/- 2.7 vs. -0.3 +/- 2.1 min(-1), P = 0.96), PaO(2) (-5 +/- 4 vs. -5 +/- 10 mmHg, P = 0.90, respectively), or PaCO(2) (-0.7 +/- 1.4 vs. -1.0 +/- 3.4 mmHg, P = 0.83, respectively). In spontaneously breathing stable patients, dopamine increased systolic blood pressure (P = 0.02) but did not influence other haemodynamic and respiratory variables. CONCLUSION: Although low-dose dopamine has been shown to depress ventilation in a variety of conditions, it does not compromise ventilation in COPD patients either breathing spontaneously or when weaned using pressure support ventilation.

[Hypertensive crisis: when and how to treat?]. / Quand et comment traiter une poussée hypertensive?

A hypertensive emergency is a situation in which uncontrolled hypertension is associated with acute end-organ damage, such as aortic dissection, pulmonary edema, acute coronary syndromes, cerebral infarction or hemorrhage, hypertensive encephalopathy, acute renal failure and eclampsia. With the exception of stroke, blood pressure must be reduced quickly, usually by using intravenous antihypertensive agents. Blood pressure reduction should be gradual while maintaining organ perfusion, which may be easily compromised in elderly and chronically hypertensive patients. In the absence of new or worsening end-organ injury, the indication of immediate therapy should be carefully evaluated. If indicated, the use of an orally long-acting antihypertensive agent is preferred to avoid an acute and unpredictable fall in blood pressure. In particular, the use of short-acting nifedipine should be condemned.

Endogenous endothelins and nitric oxide in hypoxic pulmonary vasoconstriction.

The effects of endothelin receptor blockade on the pulmonary circulation have been reported variably, possibly in relation to a more or less important associated release of endogenous nitric oxide (NO). The aim of this study was to test whether endothelin antagonism would inhibit hypoxic pulmonary vasoconstriction, and if it would not, then would it do so after NO synthase inhibition. Hypoxic pulmonary vasoconstriction (HPV) was evaluated in anesthetised dogs by the increase in the mean pulmonary artery pressure (Ppa) minus occluded Ppa (Ppao) gradient in response to hypoxia (inspiratory oxygen fraction of 0.1) at constant pulmonary blood flow. Bosentan, an endothelin A and B receptor antagonist, did not affect baseline Ppa, Ppao or systemic arterial pressure (Psa) and did not alter HPV (n=8). The NO synthase inhibitor N(G)-nitro-L-arginine (L-NA) did not affect baseline Ppa and Ppao, but increased Psa and enhanced HPV (n=12). The addition of bosentan in these dogs did not affect baseline Ppa or Ppao, but decreased Psa and inhibited HPV. Exhaled NO was decreased by L-NA and by bosentan and abolished by L-NA+bosentan (n=9). The authors conclude that endogenous nitric oxide is released by, and opposes the vasoconstricting effects of, endothelins in vivo, reducing systemic blood pressure and limiting hypoxic pulmonary vasoconstriction.

Matrix metalloproteinase 13 activity is associated with poor prognosis in colorectal cancer.

AIMS: The matrix metalloproteinases (MMPs) are a family of proteolytic enzymes collectively capable of degrading all extracellular matrix components, in particular fibrillar collagen. The importance of this group of proteins in the processes of tumour invasion and metastasis is now widely acknowledged. MMP-13 (collagenase 3) has a central role in the MMP activation cascade. The purpose of this study was to investigate the presence and activity of MMP-13 in colorectal cancer and relate these to clinicopathological features. METHODS: Immunohistochemistry for MMP-13 was performed on formalin fixed, paraffin wax embedded sections of a large series of colorectal cancers (n = 249), all of which had uniform clinical and pathological information available. Immunoreactivity to MMP-13 was detected with a monoclonal antibody to MMP-13 using a Dako TechMate 500 automated immunostaining system. The presence and cellular localisation of MMP-13 was assessed using a semiquantitative scoring system. Gelatin zymography was used to detect and measure MMP-13 activity. The zymography was performed on a subset of the cases studied by immunohistochemistry using two groups of 10 paired Dukes's C tumours and normal samples, selected by either having "good" or "poor" survival. RESULTS: Immunoreactivity to MMP-13 was identified in 91% of cases and immunoreactivity was localised to the cytoplasm of tumour cells. A high MMP-13 staining score showed a trend towards poorer survival. Tumours had significantly greater MMP-13 activity compared with normal colonic mucosa (p < 0.001). Furthermore, the tumour to normal tissue ratio was significantly higher in the poor survival group (p = 0.02). CONCLUSIONS: These results show that MMP-13 is frequently present and active in colorectal cancer and suggest that the activity of MMP-13 is associated with poorer survival in colorectal cancer.