Recycling of arterial grafts during reoperative coronary artery operations

BACKGROUND: To overcome problems of lack of conduit and to maximize the number of arterial anastomoses in coronary reoperations we reused previously placed arterial grafts. METHODS: Sixteen patients were identified from February 1994 to July 1997. Mean age was 62.8 years (range, 44 to 75 years). Fifteen (94%) were in Canadian Cardiovascular Society angina class III or IV. The mean interval from primary to secondary operation was 8.5 years (range, 3 to 12 years). Eleven patients had a patent internal mammary artery graft used as the recipient for a proximal Y anastomosis. In 3 cases an arterial graft was reimplanted distally on the same coronary vessel and in 2 onto different coronary vessels. One patient had a combination of these techniques. Five patients required venous conduit. RESULTS: There were no deaths. Mean length of intensive care stay was 69 hours (range, 24 to 144) and mean hospital stay was 14 days (range, 10 to 28 days). All patients were discharged home. Follow-up averages 13 months (range, 2 to 43 months). Twelve patients (75%) are now in Canadian Cardiovascular Society angina class I and 3 (19%) in class II. CONCLUSIONS: Reusing arterial conduits during coronary reoperations is possible with minimal in-hospital morbidity and satisfactory results in terms of freedom from angina. Using these techniques can help overcome the problems of inadequate conduit and maximize the number of arterial anastomoses that can be made per patient.     

Pseudomyxoma peritonei. A review

Pseudomyxoma peritonei is a rare disease characterized by the presence of a large mucin component within the abdomen. Recent pathological and genetic advances indicate that they originate from an appendiceal adenoma or adenocarcinoma. Their prognostic is worse than ovarian border-line mucinous tumors (with which they are frequently confused). Currently, the histologic aspect permits to separate the diffuse peritoneal adenomucinosis (DPAM) originating from adenomas, with a relatively benign course, from the mucinous peritoneal carcinomatosis (MPC) originating from adenocarcinomas, with a very poor prognosis. Paradoxically, the treatment of these two diseases are rather similar, with supra-radical surgery as frequently as possible. This type of surgery allows to reach a crude 5-year survival comprised between 50% and 70%, with very different results according to the DPAM-type or the MPC-type. The adjunction of an intraperitoneal chemo-hyperthermia is logical for these two types of disease and probably increases the survival rate.     

Executive function in Parkinson's disease and subcortical disorders

Changes in cognitive function that accompany the progression of subcortical disorders such as Parkinson's disease are often overlooked in the early stages because of a "context of discovery" that accompanies the diagnostic progress. This article discusses the nature of that context, a subcortical cognitive profile, and the contribution of executive function failure to that profile. The utility of using brief assessments of executive function and other measures, such as a brief screen for apathy, are shown with Parkinson's disease patients. Several suggestions are provided for means by which clinicians can help patients, caregivers, and families adjust to patients' impairments in executive function.     

Renal findings on radiological followup of patients with Beckwith-Wiedemann syndrome

PURPOSE: The Beckwith-Wiedemann syndrome is most commonly characterized by macroglossia and abdominal wall defect(s), and it carries a predisposition to embryonal tumors, including Wilms tumor. We report our experience with the character and incidence of renal disease in patients with the Beckwith-Wiedemann syndrome, and discuss the role of radiological followup. MATERIALS AND METHODS: We reviewed the medical records of all patients diagnosed with the Beckwith-Wiedemann syndrome who were treated at our institution between March 1979 and February 1998. Radiological followup consisted of renal ultrasound at approximately 3 to 6-month intervals with the addition of computerized tomography or magnetic resonance imaging (MRI) in patients with an indeterminate lesion(s) or nephrogenic rest(s). RESULTS: A total of 29 patients were identified. Of these cases renal ultrasound showed normal kidneys bilaterally in 19 (70%), simple cysts in 5 (19%), indeterminate lesion(s) in 2 (7%) and nephrocalcinosis in 1 (4%). Nephrogenic rests were followed with MRI in 1 patient, and 1 in whom a 2 cm. mass was revealed by followup MRI underwent partial nephrectomy and chemotherapy for stage I Wilms tumor. CONCLUSIONS: The 3.7% incidence of Wilms tumor in our patients with the Beckwith-Wiedemann syndrome is similar to that in previously published reports. Aggressive follow-up by a sensitive radiological technique is warranted in cases of the Beckwith-Wiedemann syndrome, and associated hemihypertrophy and/or nephromegaly with or without evidence of a Wilms tumor precursor. The detection of suspected malignant disease at an early stage may permit curative nephron sparing surgery.     

Nitric oxide modulates Na+, K+-ATPase activity through cyclic GMP pathway in proximal rat trachea

The present work demonstrated that nitric oxide (NO) modulates Na+, K+-ATPase activity in the proximal rat trachea. Sodium nitroprusside induced concentration-dependent (10-100 microM) stimulation in proximal trachea Na+, K+-ATPase activity. The effect was specific for Na+, K+-ATPase since Mg-ATPase activity was unaffected. This NO-donor changed neither Na+, K+-ATPase nor Mg-ATPase activity in the distal segment. The modulatory action on Na+, K+-ATPase induced by sodium nitroprusside was linked to an increase in nitrates/nitrites and cyclic GMP levels in proximal segments. Modulation of proximal Na+, K+-ATPase activity by sodium nitroprusside was mimicked by S-nitroso-N-acetylpenicillamine (100 microM) and 8-bromo-cyclic GMP (100 microM). Both sodium nitroprusside and 8-bromo-cyclic GMP effects on Na+, K+-ATPase activity of proximal segments of trachea were blocked by 2 microM of KT 5823 (a cyclic GMP-dependent protein kinase inhibitor), but not by 0.5 microM of KT 5720 (a cyclic AMP-dependent protein kinase inhibitor). Both kinase inhibitors decreased proximal Na+, K+-ATPase activity, but did not change Mg-ATPase activity. Okadaic acid (1 microM), a phosphatase-1 inhibitor, increased proximal Na+, K+-ATPase but not Mg-ATPase activity. The effect of okadaic acid was non-additive with that of 8-bromo-cGMP on Na+, K+-ATPase activity. Our results suggest that NO modulates proximal rat trachea Na+, K+-ATPase activity through cyclic GMP and cyclic GMP-dependent protein kinase.     

Central Nervous System Effects of Ginkgo Biloba, a Plant Extract

Extracts of Ginkgo biloba (EGb) are among the most prescribed drugs in France and Germany. EGb is claimed to be effective in peripheral arterial disorders and in "cerebral insufficiency." The mechanism of action is not yet well understood. Three of the ingredients of the extract have been isolated and found to be pharmacologically active, but which one alone or in combination is responsible for clinical effects is unknown. The recommended daily dose (3 x 40 mg extract) is based more on empirical data than on clinical dose-findings studies. However, despite these, according to double-blind, placebo-controlled clinical trials, EGb has therapeutic effects, at least, on the diagnostic entity of "cerebral insufficiency," which is used in Europe as synonymous with early dementia. To determine whether EGb has significant pharmacological effects on the human brain, a pharmacodynamic study was conducted using the Quantitative Pharmacoelectroencephalogram (QPEEG(R)) method. It was established that the pharmacological effects (based on a predetermined 7.5--13.0-Hz alpha frequency band in a computer-analyzed electroencephalogram = CEEG(R)) of EGb on the central nervous system (CNS) are significantly different than placebo, and the high and low doses could be discriminated from each other. The 120-mg, but particularly the 240-mg, single doses showed the most consistent CNS effects with an earlier onset (1 h) and longer duration (7 h). Furthermore, it was established that the electrophysiological effects of EGb in CNS are similar to those of well-known cognitive activators such as "nootropics" as well as tacrine, the only marketed "antidementia" drug currently available in the United States.     

Pharmacokinetics and Biodistribution of Oligonucleotide Adsorbed onto Poly(isobutylcyanoacrylate) Nanoparticles After Intravenous Administration in Mice

Purpose. The goal of this study was to evaluate the ability of nanoparticles to be used as a targeted delivery system for oligonucleotides. Methods. Pharmacokinetic and tissue distribution were carried out in mice by measuring the radioactivity associated to the model oligothymidylate ³³P-pdT₁₆ loaded to poly(isobutylcyanoacryrate) (PIBCA) nanoparticles. In addition, we have used a TLC linear analyzer to measure quantitatively on a polyacrylamide gel electrophoresis, the amount of non degraded pdT₁₆ Results. Organ distribution study has shown that nanoparticles deliver ³³P-pdT₁₆ specifically to the liver reducing its distribution in the kidney and in the bone marrow. Nanoparticles could partially protect pdT₁₆ against degradation in the plasma and in the liver 5 min after administration, whereas free oligonucleotide was totally degraded at the same time. Conclusions. Nanoparticles protect oligonucleotides in vivo against degradation and deliver them to the liver.     

Sonographic evaluation of renal masses: Correlations with angiography

The value of sonography in the diagnosis of renal masses in a series of 119 consecutive histologically confirmed cases is presented. Sonography correctly identified 92% of the cystic and 90% of the solid renal masses. Causes of incorrect diagnoses included lesions smaller than 2 cm, masses in the left upper pole, diffusely infiltrating urothelial tumors, echogenic fatty lesions (early in our experience), and acute abscesses and hematomas. Angiography in the same series of cases correctly diagnosed 80% of the cystic and 88% of the solid renal masses. Avascular lesions were the main cause for equivocal or incorrect angiographic diagnoses. We conclude that sonography is more definitive than angiography in the diagnosis of avascular masses, while angiography excels when the lesion is vascular or small. Combining the sonographic and angiographic findings allowed accurate diagnosis in over 99% of the cases.     

Effects of α2-adrenoceptor agonists on locus coeruleus firing rate and brain noradrenaline turnover in N-ethoxycarbonyl-2-ethoxy-1,2-dihydroquinoline (EEDQ)-treated rats

Summary Previous studies have shown that a low dose of the alkylating compound N-ethoxycarbonyl-2-ethoxy1,2-dihydroquinoline (EEDQ) reduces the density of ₂-adrenoceptors in rat cerebral cortex and antagonizes the effects of an ₂-adrenoceptor agonist on noradrenaline release in rat cortical slices. In the present study, a corresponding dose of EEDQ (1 mg/kg, s. c., 24 h) was shown to reduce the effect of the ₂-adrenoceptor agonists clonidine and guanfacine on noradrenaline turnover in rat brain while not affecting the inhibitory effect of clonidine on locus coeruleus (LC) cell firing. When considerably higher doses of EEDQ were administered (10 and 20 mg/kg, s. c., 24 h) not only the biochemical but also the electrophysiological effects of clonidine were markedly reduced (or even reversed). The data support the notion that EEDQ decreases the responsiveness of brain ₂-adrenergic receptors; moreover, they indicate that ₂-adrenoceptors regulating LC activity are characterized by a larger receptor reserve or are less sensitive to the influence of alkylation than are the population of ₂-adrenoceptors regulating noradrenaline utilization. Send offprint requests to G. Engberg, at the above address     

Liposomes and Nanoparticles in the Treatment of Intracellular Bacterial Infections

The treatment of infections caused by obligate or facultative intracellular microorganisms is difficult because most of the available antibiotics have either poor intracellular diffusion and retention or reduced activity at the acidic pH of the lysosomes. The need for antibiotics with greater intracellular efficacy led to the development of endocytosable drug carriers, such as liposomes and nanoparticles, which mimic the entry path of the bacteria by penetrating the cells into phagosomes or lysosomes. This Review assesses the potential of liposomes and nanoparticles in the targeted antibiotic therapy of intracellular bacterial infections and diseases and the pharmaceutical advantages and limitations of these submicron delivery systems.