This study was designed to investigate whether the addition of nitroglycerin to vasopressin infusion could avoid the deleterious systemic effects of vasopressin while maintaining or enhancing the therapeutic benefits of portal pressure reduction. The effect of nitroglycerin on splanchnic and systemic hemodynamics was studied in cirrhotic patients and portal hypertensive dogs receiving i.v. vasopressin. During i.v vasopressin infusion (0.4 units per min), the cardiac output decreased in patients by 14% from 7.6 +/- 0.9 (mean +/- S.E.) to 6.5 +/- 0.7 liters per min, p less than 0.01, the mean arterial pressure increased 21% from 87 +/- 2 to 105 +/- 4, p less than 0.01, and the heart rate decreased 11% from 79 +/- 3 to 71 +/- 3, p less than 0.01. The administration of sublingual nitroglycerin (0.4 mg) returned all the systemic hemodynamic parameters to baseline values. In dogs, vasopressin infusion significantly reduced portal pressure and flow while increasing portal venous resistance. Nitroglycerin when added to the vasopressin infusion reduced portal venous resistance and further decreased portal pressure in dogs. In patients, vasopressin reduced the hepatic blood flow (44%), wedged hepatic venous pressure (11%), and the gradient between wedged and free hepatic venous pressures (23%). Nitroglycerin administration caused a further reduction of the wedged hepatic venous pressure (23.6 +/- 2.3 to 21.1 +/- 2.0, 11%, p less than 0.01). There was a small but not significant further decline (7%) in the hepatic venous pressure gradient. These results provide evidence that the addition of nitroglycerin to an i.v. infusion of vasopressin reversed the detrimental effects of vasopressin while preserving the beneficial effects.

Animals↗

PubMedDate not supplied

Reticuloendothelial system phagocytic activity in cirrhosis and its relation to bacterial infections and prognosis.

The reticuloendothelial system phagocytic activity, estimated by the plasma elimination rate constant of 99mtechnetium-sulfur colloid, was studied in 41 decompensated cirrhotics and 10 normal subjects. The results were related to the incidence and type of bacterial infections occurring during hospitalization and follow-up, and to survival. The elimination rate constant of 99mtechnetium-sulfur colloid was lower in cirrhotic patients (0.168 +/- 0.007) (means +/- S.E.) than in normal subjects (0.220 +/- 0.005) (p less than 0.01). Cirrhotics were divided into two groups. Group I (16 patients) and Group II (25 patients) had normal or reduced elimination rate constant of 99mtechnetium-sulfur colloid, respectively. Both groups were similar in relation to clinical and biochemical data, hepatic blood flow, and wedged hepatic venous pressure. However, the liver scan and the elimination rate constant of indocyanine green were more altered in Group II. Patients in Group II developed acute bacterial infections more frequently than did patients in Group I. During hospitalization (24 +/- 2 days), bacteremia occurred in six patients in Group II and in none in Group I (p less than 0.05). During follow-up (28 +/- 3 months), 5 patients in Group II and none in Group I developed bacteremia (p less than 0.05). The cumulative survival rate of Group I patients was higher (p less than 0.05) than that of Group II patients at 3 months (100 vs. 80%), 6 months (94 vs. 68%), 24 months (74 vs. 42%), and 48 months (68 vs. 34%). We suggest that decompensated cirrhotics with depressed reticuloendothelial system phagocytic activity are at great risk to acquire bacteremia, and that reticuloendothelial system phagocytic activity has prognostic value in cirrhosis.

Bacterial Infections↗

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Effects of propranolol on azygos venous blood flow and hepatic and systemic hemodynamics in cirrhosis.

The effects of propranolol on blood flow through gastroesophageal collaterals and on systemic and hepatic hemodynamics were investigated in 23 cirrhotic patients with portal hypertension. Gastroesophageal collateral blood flow was evaluated by the measurement of azygos venous blood flow by continuous thermal dilution. Azygos venous blood flow was markedly increased in these patients (544 +/- 48 ml per min, as compared with 132 +/- 18 ml per min in subjects without portal hypertension (p less than 0.001). Propranolol at doses achieving effective beta-blockage (83 +/- 5 mg) (mean +/- S.E.M.) markedly reduced azygos venous blood flow (to 354 +/- 34 ml per min, p less than 0.001). Reduction of azygos venous blood flow (-34.2 +/- 3.6%) was significantly greater (p less than 0.01) than reductions in cardiac output (-22.6 +/- 1.9%), hepatic venous pressure gradient (-11.5 +/- 2.4%) and hepatic blood flow (-13.4 +/- 7.4%). The hemodynamic effects of propranolol were not related to plasma norepinephrine levels. Reduction of gastroesophageal collateral blood flow may be the mechanism by which oral propranolol therapy reduces the risk of repeated episodes of variceal bleeding in cirrhotic patients with portal hypertension.

Azygos Vein↗

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Cefotaxime is more effective than is ampicillin-tobramycin in cirrhotics with severe infections.

We compared the effectiveness and incidence of nephrotoxicity of ampicillin-tobramycin and cefotaxime in 73 cirrhotics who had severe bacterial infection. Most of these patients had spontaneous peritonitis and/or bacteremia. Patients were randomly allocated into two groups. Group I included 36 patients treated with ampicillin-tobramycin and Group II comprised 37 patients treated with cefotaxime. Patients from both groups were similar with respect to clinical data, standard liver and renal function tests, types of infection and isolated organisms. Ninety-two per cent of bacteria isolated in Group I and 98% of those isolated in Group II were susceptible in vitro to ampicillin-tobramycin and to cefotaxime, respectively. Ampicillin-tobramycin cured the infection in 56% of Group I patients, and cefotaxime in 85% of Group II patients (p less than 0.02). Five patients treated with ampicillin-tobramycin, and none treated with cefotaxime developed superinfections (p = 0.024). Nephrotoxicity (impairment of renal function associated with an increase of urinary beta 2-microglobulin to over 2,000 micrograms per liter) occurred in two patients in Group I and none in Group II. These results suggest that broad-spectrum cephalosporins should be considered as first choice antibiotics in cirrhotic patients with severe infections.

Adult↗

PubMedDate not supplied

Oral, nonabsorbable antibiotics prevent infection in cirrhotics with gastrointestinal hemorrhage.

To investigate if oral, nonabsorbable antibiotics prevent bacterial infections in cirrhotics with gastrointestinal hemorrhage, 140 consecutive patients were randomly allocated into two groups: 68 patients (Group I) were given oral, non absorbable antibiotics (gentamicin + vancomycin + nystatin or neomycin + colistin + nystatin) from the inclusion into the trial up to 48 hr after cessation of the hemorrhage, or until emergency surgery or death in those cases who continued bleeding; and 72 patients (Group II) did not receive oral, nonabsorbable antibiotics. Both groups were similar in relation to clinical and laboratory data and characteristics of the hemorrhage. The incidence of infection was significantly lower in Group I than in Group II (11 patients in Group I and 25 in Group II developed proved infections; p less than 0.025). This difference was due to the fact that spontaneous bacteremia and peritonitis and urinary tract infection caused by enteric bacteria occurred almost exclusively in Group II. Two patients of Group I and 10 of Group II developed spontaneous bacteremia and/or peritonitis caused by enteric bacteria (p less than 0.025). These results indicate that prophylactic administration of oral, nonabsorbable antibiotics markedly reduces the incidence of infections caused by enteric bacteria in cirrhotic patients with gastrointestinal hemorrhage.

Administration, Oral↗

PubMedDate not supplied

Anastrozole as neoadjuvant therapy for patients with hormone-dependent, locally-advanced breast cancer.

BACKGROUND: We investigated the efficacy and safety of anastrozole as neoadjuvant therapy in a group of postmenopausal patients with locally-advanced breast cancer. PATIENTS AND METHODS: This was an open-label trial, which recruited patients with histopathologically-confirmed unilateral, locally-advanced, estrogen-receptor-positive breast cancer (stage IIIA/B). All patients received anastrozole 1 mg/day for 3 months, after which the clinical response was evaluated. All patients with a complete or partial clinical response (cCR or cPR) underwent surgery (radical modified mastectomy), after which patients continued with the same therapy for two years or until progression. Primary end points were clinical response rate (cCR + cPR), surgery rate, pathological complete response rate and tolerability profile. RESULTS: cCR and cPR were seen in 61/112 (54.5%) and 32/112 (28.6%) patients (n=112), respectively, giving an objective response rate of 93/112 (83%) patients. Following surgery in responding patients, 14/61 patients (23%) had a pathological CR and 47/61 (77%) patients had a pathological PR. CONCLUSION: Neoadjuvant anastrozole treatment was highly effective and well-tolerated in postmenopausal women with hormone-dependent locally-advanced breast cancer.

Aged↗

PubMedDate not supplied

Alpha-fetoprotein in the early diagnosis of hepatocellular carcinoma.

Increased AFP levels in patients with hepatocellular carcinoma are mainly related to tumor size and in a lesser degree, to AST levels. Abnormal and/or diagnostic AFP levels will be observed in a reduced proportion of patients with small HCC (less than 5 cm). Therefore, AFP measurement is of little value in the early detection of HCC.

Aged↗