Cardiovascular effects of beta 3-adrenoceptor stimulation in perinephritic hypertension

BACKGROUND: A new beta 3-adrenoceptor (beta3-AR) has been shown to mediate peripheral vasodilation. This study was conducted to evaluate effects of the beta3-AR agonist, SR58611 in normal and hypertensive dogs. MATERIALS AND METHODS: In protocol 1, SR58611 was infused in normal dogs after placebo, after beta1/beta2 blockade with nadolol, after beta1/beta2/beta3 blockade with bupranolol and after combined autonomic blockade (CAB). In protocol 2, perinephritic hypertension was produced in dogs, which received SR58611 at 3 and 6 weeks of hypertension. Effects of SR58611 were evaluated at 7 weeks of hypertension after CAB. RESULTS: In normal dogs, SR58611 produced a dose-dependent decrease in mean aortic pressure (AOP) (from 116 +/- 19 to 100 +/- 19 mmHg, - 14%; P < 0.05) that was accompanied by baroreflex activation (heart rate increased by 70%; P < 0.01). This hypotensive effect resulting from peripheral vasodilation persisted after nadolol or CAB while baroreflex activation was blunted or abolished. A biphasic response of cardiac output, characterized by a rise and a decline (P < 0.05) reflected a reduction in after- and pre-load. After CAB, SR58611 did not modify cardiac contractility. SR58611 stimulated lipolysis as reflected by a 4-fold increase in blood free fatty acids (FFA) (P < 0.0005). Under CAB, the rise of FFA was reduced (P < 0.01). In hypertensive dogs, SR58611 produced a dose-dependent decrease in mean AOP (from 168 +/- 32 to 125 +/- 35 mmHg; - 26%, P < 0.0001), that was greater than in normal dogs (P < 0.05). Reflex-mediated tachycardia also occurred but at higher blood pressure values. Blood FFA rose similarly (P < 0.0001). Under CAB, heart rate remained unchanged but SR58611 still induced a decrease (P < 0.0001) in mean AOP concomitantly with a rise of (dP/dt)/DP40 (P < 0.005), an effect not observed in normal dogs. CONCLUSIONS: Beta3-AR stimulation exerts hypotensive effects, increases cardiac contractility and stimulates lipolysis in hypertensive dogs.     

Long-term terlipressin administration improves renal function in cirrhotic patients with type 1 hepatorenal syndrome: a pilot study

BACKGROUND: Hepatorenal syndrome (HRS) is a severe complication of liver cirrhosis. Recently, ornipressin, a potent splanchnic vasoconstrictor, was reported to improve renal function in patients with HRS. However, this treatment is associated with a high incidence of vascular complications. Terlipressin is thought to be as effective as ornipressin with less systemic complications. AIMS: To evaluate the effectiveness and safety of terlipressin administration in cirrhotic patients with type 1 HRS. PATIENTS: Twelve consecutive patients fulfilling HRS criteria of the International Ascites Club were included in the study. Median plasma creatinine and sodium, urine volume and sodium before treatment were 3.4 mg% (2.5-4.0); 127 mEq/l (124-130), 500 ml/24 h (100-1031) and 7 mEq/24 h (1-17). METHODS: Terlipressin was administered i.v. 2 mg bid in 8 patients and tid in 4 others for at least one week and up to 2 months. RESULTS: After one week of treatment median plasma creatinine decreased to 1.8 mg% (1.3-2.1) together with an increase in urine volume, sodium excretion, creatinine and free-water clearance. Three patients underwent successful liver transplantation with a near normal renal function after 34, 36 and 111 days. The 9 other patients died during follow-up (4 from sepsis, 2 from digestive bleeding and 3 from liver failure). No ischaemic complications were encountered during the treatment. CONCLUSIONS: Long-term terlipressin administration is safe and effective to control type 1 HRS. However, it does not cure the underlying disease and therefore, may only be considered as a bridge to a definitive treatment as liver transplantation.     

Unusual splenic complication of acute pancreatitis.

Splenic complications of acute pancreatitis are rare. We describe a spontaneous subcapsular splenic laceration during an episode of acute pancreatitis, without any evidence of one of the currently reported predisposing factors. Its spontaneous resolution suggests that conservative therapy can be proposed in such complications.     

Liver transplantation for acute liver failure in adults

Acute liver failure is a challenging clinical condition, associated with high morbidity and mortality. In well-selected patients, LT (LT) is the only therapeutic which has been demonstrated to improve patient survival. Clichy and King's College criteria are the two mains scoring systems used to select the patients for liver transplantation. Both models achieve high specificity but remain associated with limited negative predictive value. Several other predictive factors have been evaluated, but none of them have been strongly validated so far. Globally, whole LT appears as the procedure of choice for patients within Clichy and/or King's College criteria. Due to the severity of the disease and its multisystemic consequences, the results of LT for fulminant liver failure remain inferior to those obtained in elective indications. Accord-ing to local conditions, namely expected waiting time before urgent transplantation and surgical expertise, living donor transplantation and auxiliary transplantations appear as valuable alternatives. These techniques have the respective potential advantages to limit the waiting period before transplantation and to avoid the need for lifelong immunosuppression when native liver recovers, but overall results remain inferior to those obtained with whole LT.     

Histopathological growth patterns of resected non-colorectal,non-neuroendocrine liver metastases: a retrospective multicenter study

Background

Distinct Histopathological Growth Patterns can be identified in liver metastases from melanoma, breast and colorectal cancers. For each of these distinct liver metastasis types the HGP has proven a biomarker for survival after partial hepatectomy, with the desmoplastic type marking favourable prognosis. Whether HGPs can be considered a pan-cancer phenomenon remains unknown. This study therefore evaluates the presence of HGPs and their prognostic value across non-colorectal non-neuroendocrine liver metastases.

Methods

A retrospective multicentre cohort study was performed in patients who underwent curative intent resection of non-colorectal non-neuroendocrine liver metastasis. HGPs were assessed on Haematoxylin and Eosin slides according to consensus guidelines and classified as desmoplastic or non-desmoplastic. Overall- and recurrence-free survival were evaluated using Kaplan–Meier and multivariable Cox regression analysis.

Results

In total, 132 patients with liver metastasis from 25 different tumour types were eligible for analysis, of which 26 (20%) had a desmoplastic HGP. Five-year OS and RFS (95%CI) were 53% (36–78%) versus 40% (30–53%), and 33% (19–61%) versus 15% (9–27%) for patients with desmoplastic compared to non-desmoplastic metastases, respectively (p?=?0.031 & p?=?0.004). On multivariable analysis (adjusted HR [95%CI]) a desmoplastic HGP was prognostic for both OS (0.46 [0.25–0.86]) and RFS (0.38 [0.21–0.69]).

Conclusions

This study demonstrates that HGPs apply to liver metastases across a wide variety of primary tumour origins. They hold a prognostic value in these cases, suggesting that HGPs could represent a pan-cancer biomarker for survival after surgical resection of liver metastases.

     

Intraoperative gamma probe detection of insulinoma in an elderly patient with pancreatic cystic lesions

Insulinoma is a rare endocrine tumour in the elderly. We report the case of an 81-year-old woman suffering from grand mal seizures. Insulinoma was suspected because plasma glucose and insulin levels were 1.5 mmol/l and 80.4 pmol/l, respectively. A pancreatic computerized tomography (CT) scan, magnetic resonance imaging (MRI) and arteriography were normal but (111)In-DTPA-octreotide scintigraphy detected a hotspot in the pancreatic tail. Intraoperative pancreatic ultrasonography and palpation were non-contributory due to multiple pancreatic cysts and nodular lesions. However, a gamma-detecting probe localized a small tumour, labelled preoperatively with (111)In-DTPA-octreotide. Intraoperative insulin measurements in portal venous blood confirmed the successful removal of an insulinoma that was 6 mm in diameter histologically. Pancreatic cystic lesions increase with age and make the intraoperative localization of the insulinoma difficult. Intraoperative gamma probe detection of the tumour labelled with (111)In-DTPA-octreotide might therefore constitute a useful surgical tool.     

Metabolic (glycaemic, lipidic) and blood pressure control in 101 type 2 diabetic patients on first admission to diabetes centres

The aim of our study was to analyse the quality of metabolic and blood pressure control in a cohort of 101 patients with type 2 diabetes (54 males; 47 females), previously followed in primary care settings and admitted for the first time to the diabetes centres of Saint-Luc (n=66) or Mont-Godinne (n=35) University Hospitals. Age and (known) duration of diabetes were 64 +/-12 and 6 +/- 7 years (mean +/- SD), respectively. Body mass index was 31 +/- 7 kg/m2. Systolic and diastolic blood pressures were 140 +/-12 and 81 +/-11 mmHg. Homeostasis model assessment (HOMA) showed insulin sensitivity at 63 +/-32% and P-cell function at 49 +/- 44% (n=34). Forty-seven percent of patients received either diet alone or combined with an oral antidiabetic monotherapy. Seven-teen percent of all patients were on insulin monotherapy or associated with oral drugs. HbAlc was 9.0 +/- 2.3%, with 22% of patients within HbAlc targets of < or = 7%. Only a subset of patients reached international targets of care in terms of blood pressure and lipidic profile, despite antihypertensive and lipid-lowering agents in 62% and 36% of patients, respectively. Forty-five percent of individuals had at least one diabetes-related long-term complication. In view of this unsatisfactory control, our results suggest that "anti-diabetic" treatment should be intensified earlier in primary care settings.     

Non-Heart-Beating Donors: An Inquiry to ICU Nurses in a Belgian University Hospital

Demand for organs for transplantation continues to be greater than supply. Non-heart-beating donation (NHBD) has been reintroduced to reverse this trend. We describe the findings of a short questionnaire that determined the attitudes and feelings of nursing staff in a department of intensive care with an established NHBD program. Despite several educational sessions, only 3% of the nurses thought they were adequately informed about NHBD. Thirty-eight percent of nurses were less comfortable with NHBD than with brain death organ donation. NHBD is an ethically controversial area but one that can improve organ availability for transplantation. Adequate education, ongoing audit, and full transparency are needed in units that use NHBD.     

Surgery in patients on long-term steroid therapy: a tentative model for risk assessment

Increased morbidity after operation has been associated with long-term steroid therapy. To determine the correlation between steroid therapy and such morbidity, the perioperative course of 55 steroid-treated patients was reviewed: 27 had bronchopulmonary disorders (group P) and 28 had non-pulmonary diseases (group NP). There were six (11 per cent) deaths, of which three were steroid related. Among the 13 non-lethal postoperative complications, eight were considered to be steroid related in group P and one in group NP. The duration of steroid therapy was for a median of 24 months (range 1-408 months) in group P and for a median of 6 months (range 1-240 months) in group NP (P less than 0.01). In contrast, the daily dose of hydrocortisone or equivalent before operation was significantly lower in group P, with a median of 0.51 mg kg-1 day-1 (range 0.20-2.56 mg kg-1 day-1) than in group NP, with a median of 1.20 mg kg-1 day-1 (range 0.23-7.38 mg kg-1 day-1) (P less than 0.01). In conclusion, bronchopulmonary disorders requiring a long duration of steroid therapy are associated with a higher risk of steroid-related complications after surgery. A convenient mathematical model is proposed which may allow a preoperative assessment of surgical risk, using steroid dose and duration of treatment.