Arterial and Venous Pharmacokinetics of Ropivacaine with and without Epinephrine after Thoracic Paravertebral Block

Background: Animal and volunteer studies indicate that ropivacaine is associated with less neurologic and cardiac toxicity than bupivacaine. Ropivacaine may offer advantages when used for thoracic paravertebral block. This study was designed to describe the pharmacokinetics of ropivacaine after thoracic paravertebral block.

Methods: Twenty female patients undergoing elective unilateral breast surgery were randomly assigned to receive a single bolus thoracic paravertebral injection of 2 mg/kg ropivacaine, with or without 5 [mu]g/ml epinephrine. Simultaneous arterial and venous blood samples were obtained for plasma ropivacaine assay. Data were analyzed with NONMEM, using two possible absorption models: conventional first-order absorption and absorption following the inverse gaussian density function.

Results: Epinephrine reduced the peak plasma concentrations and delayed the time of peak concentration of ropivacaine in both the arterial and venous blood. The time course of drug input into the systemic circulation was best described by two inverse gaussian density functions. The median bioavailability of the rapid component was approximately 20% higher when epinephrine was not used. The mean absorption times were 7.8 min for the rapid absorption phase and 697 min for the slow absorption phase, with wide dispersion of the absorption function for the acute phase. The half-time of arterial-venous equilibration was 1.5 min.     

One-shot percutaneous ethanol injection of liver tumors under general anesthesia: Preliminary data on efficacy and complications

Purpose: To verify the efficacy of ultrasound (US)-guided injection of large amounts of ethanol into large or multiple liver lesions, in a single session under general anesthesia (one-shot PEI) for percutaneous ablation of hepatic tumors. Methods: Twenty-nine patients (27 with 51 hepatocellular carcinoma (HCC) nodules on cirrhosis, diameter range 1.0<+>–<+>9.0 cm; two patients with a single metastasis from the gastroenteric tract, 5.0 and 9.0 cm, respectively, in diameter) were treated with one-shot PEI. Results: The total volume of alcohol delivered per patient ranged from 16 to 210 ml. Mean ethanol volume in all patients was 49 ml. Dynamic computed tomography (CT) examination showed complete necrosis in 41 of 50 lesions. Two patients died of hypovolemic shock due to massive upper gastrointestinal bleeding, 3 and 7 days, respectively, after the interventional procedure. All the remaining patients are alive (follow-up 5<+>–<+>14 months) except one who died of liver failure 5 months after. New HCC nodules occurred in six patients within 6 months and one intralesional relapse was recorded. Conclusion: In this preliminary experience, one-shot PEI is as effective in inducing liver tumor necrosis as traditional PEI; its advantages are shorter treatment time and the capability of treating larger and multiple liver lesions.     

Study on tissue concentrations of antibiotics: bacampicillin in gingiva and maxillary bones

21 patients, whose age ranged from 17 to 60 years and who had not been previously treated with antibiotics or other drugs, received bacampicillin as a perioperative prophylaxis for minor operations in the oral cavity. Four oral doses of bacampicillin were administered: each dose of 800 mg every 12 h, and the last dose was administered 2 h before surgery. To assess bacampicillin serum concentrations two blood samples were collected from each patient: the first sample was obtained 1 h before surgery and the second one during surgery. Together with the second blood sample, small quantities of gingiva and bone were obtained from each patient to also assess the antibiotic concentrations in these tissues (microbiological method). The results show that bacampicillin reaches high concentrations in both the blood and tissues studied by us, and that a direct correspondence exists between blood and gingival and bone tissue concentrations. Furthermore, it should be noted that no postoperative infections developed in our patients. These results lead to the conclusion that bacampicillin appears to be a suitable drug in the therapy of dental infections.     

Carers, ethics and dementia: a survey and review of the literature.

BACKGROUND: Much has been written on ethical issues in dementia, but usually from the point of view of the various professionals involved. Whilst there has been an increasing amount of interest in the psychosocial problems that face the carers of people with dementia, the ethical nature of some of these problems has largely been ignored. OBJECTIVE: To review the literature on ethical issues in dementia from the perspective of the main, non-professional carers of people with dementia. METHOD: A systematic literature search using Medline, Clinpsych and CINAHL databases between 1982 and 2000. A pilot study of carers. RESULTS: The lay perspective provides both a wide variety of issues and unique approaches. Although in the literature quantitative research answers some questions, it is qualitative research that deepens our understanding of the issues from the perspective of carers. CONCLUSION: It is particularly qualitative research that brings out the ethical issues for carers, which tend to be more varied than the ethical issues raised in the professional literature. Awareness of such issues could inform and shape the support given to carers.     

Suppressor response in lepromatous leprosy patients: role of Leu 2a cells.

The contribution of non-specific suppressor mechanisms to the overall immunoregulatory defect observed in lepromatous leprosy was evaluated. Con A-induced suppression was assayed using the standard two-stage test in 27 lepromatous leprosy patients, 19 of them during the quiescent stage (LL) and eight during erythema nodosum lepromatosum (ENL). Lymphocytes from normal individuals react in this assay, yielding higher suppression as the numbers of Con A-induced suppressor cells (Leu 2a+ cells) increase. In contrast, two patterns of response were observed in both LL and ENL patients: those giving lower suppression as the number of suppressor cells increased (LL-A and ENL-A) and those responding with the normal pattern (LL-B and ENL-B). The abnormal dose-response profile was not related to the disease stage, as both ENL and LL patients were included in groups with normal or atypical response. Reaction of the potential suppressor cells with anti-Leu 2a antibody abolished suppression in LL-B and normals, whereas Con A-induced suppression was unchanged or higher in ENL-A, ENL-B and LL-A, indicating that in these patients Leu 2a+ cells interfered with the generation of Con A-induced suppression. The contribution of spontaneous suppression was examined and it was shown that suppressor activity in the absence of Con A stimulus was higher in ENL (both ENL-A and ENL-B) and LL-A. Thus, it appears that the occurrence of high spontaneous suppressor activity, probably related to in vivo activation, is associated with a relative inability to generate de novo suppression after Con A stimulation in these patients.     

Molecular characterization of Waldenstrom's macroglobulinemia reveals frequent occurrence of two B-cell clones having distinct IgH VDJ sequences.

PURPOSE: Malignant B lineage cells in Waldenstrom's macroglobulinemia (WM) express a unique clonotypic IgM VDJ. The occurrence of biclonal B cells and their clonal relationships were characterized. EXPERIMENTAL DESIGN: Bone marrow and blood from 20 WM patients were analyzed for clonotypic VDJ sequences, clonal B-cell frequencies, and the complementary determining region 3 profile. RESULTS: Two different clonotypic VDJ sequences were identified in 4 of 20 WM. In two cases, partner clones had different VDJ rearrangements, with one clonotypic signature in bone marrow and a second in blood. For both cases, the bone marrow clone was hypermutated, whereas the blood clone was germ line or minimally mutated. In two other cases, partner clones shared a common VDJ rearrangement but had different patterns of somatic mutations. They lacked intraclonal diversity and were more abundant in bone marrow than in blood. VDJ mutation profiles suggested they arose from a common IgM progenitor. Single-cell analysis in one case indicated the partner clones were reciprocally expressed, following rules of allelic exclusion. CONCLUSIONS: The existence of two B-cell clones having distinct VDJ sequences is common in WM, suggesting that frequent transformation events may occur. In two cases, the partner clones had distinct tissue distributions in either blood or bone marrow, were of different immunoglobulin isotypes, and in one case exhibited differential response to therapy. The contributions of each clone are unknown. Their presence suggests that WM may involve a background of molecular and cellular events leading to emergence of one or more malignant clones.