The detection and identification of 42,43,44,45,46,47,55-heptanor-41-oxoyessotoxin,a new marine toxin from adriatic shellfish,by liquid chromatography-mass spectrometry

The diarrhetic shellfish toxin composition in the digestive glands of mussels collected in June 2001 from the Northern Adriatic sea was investigated by high-performance liquid chromatography coupled with electrospray ion trap mass spectrometry. Along with known yessotoxins (1, 3-6), identified by comparison of their retention times and mass spectra with those of appropriate standards, a new marine toxin, 42,43,44,45,46,47,55-heptanor-41-oxoyessotoxin, 7, was detected. MS/MS experiments were used to gain structural information. 7 represents a new addition to the class of yessotoxins.     

Teratogenic potential of the newer antiepileptic drugs: what is known and how should this influence prescribing?

The treatment of women of childbearing age who have epilepsy raises many questions because of the interactions between epilepsy, antiepileptic therapy and different aspects of reproductive life. Menstrual cycle disorders and reduced fertility have been partially ascribed to antiepileptic drugs (AEDs). Furthermore, most AEDs induce the cytochrome P450 (CYP) enzymatic system, altering the metabolism of sex hormones and contributing to the failure of oral contraceptives. Pregnancy represents, in this context, the most critical period because of the well known teratogenic potential of all established AEDs. For most of these drugs no specific patterns of malformations have been identified, although during the past few decades basic knowledge has been acquired, particularly concerning the mechanisms of AED-induced teratogenesis and related risk factors. These issues form the basis of the current guidelines for the management of epilepsy in pregnant women. In the past decade, several new AEDs have been introduced into clinical practice. For a number of reasons, these drugs appear to be more favourable than the older ones as treatments for epilepsy in women of childbearing age. They possess a good pharmacokinetic profile that makes them more stable during pregnancy, and they have a low potential for interaction with other drugs. They are also less likely than the older AEDs to be metabolised to compounds that are teratogenic. Furthermore, most of them do not possess antifolate properties. With the exception of topiramate and vigabatrin, the newer AEDs do not appear to be teratogenic in animals when administered in subtoxic doses. However, animal teratology may not be a reliable predictor of human teratogenicity, and there is a significant lack of information regarding the teratogenic profile of these newer agents in humans. Because clinical experience with these agents is limited, it is advisable to avoid exposure of the embryo to these drugs when pregnancy is planned. The establishment of pregnancy registries could allow for the rapid collection of data related to the administration of new AEDs in pregnancy and the outcomes of such exposure.     

A new rapid bedside assay for quantitative testing of D-Dimer (Cardiac D-Dimer) in the diagnostic work-up for deep vein thrombosis

The accuracy of a new bedside, rapid and quantitative D-Dimer assay (Cardiac D-Dimer) was evaluated in outpatients with clinically suspected deep vein thrombosis (DVT); VIDAS test was used as reference method. Eighty consecutive outpatients with suspected DVT of a lower limb were included in the study. Patients were classified as DVT positive or negative according to results of objective test (serial CUS), pretest clinical probability and 3-month follow-up. DVT was diagnosed in 32/80 patients (40%). The performance of the two D-Dimer assays was comparable, as indicated by the areas under the ROC curves (0.89 and 0.88, for Cardiac D-Dimer and VIDAS, respectively) and the coefficient of correlation (r=0.91). The reproducibility of the test was acceptable (from 6.2% to 12.0%). The sensitivity and negative predictive values were 100% for both tests. The specificity (SP) and positive predictive values (PPV) were similar (SP: 50.0% and 52.0%, PPV: 57.1% and 58.2%, for Cardiac D-Dimer and VIDAS, respectively). The Cardiac D-Dimer test proved to be very accurate and produced results fully comparable to those obtained with the VIDAS test. Since the test can be directly performed in the emergency room within a few minutes, it seems to have great clinical potential. The place of this assay in the diagnostic strategy of DVT remains to be determined in prospective management studies.     

Intravascular hemolysis in patients with new-generation prosthetic heart valves: a prospective study

OBJECTIVE: A prospective clinical study was designed to assess the frequency and severity of intravascular hemolysis in patients with new-generation, normally functioning prosthetic heart valves. METHODS: Hemolysis was evaluated in 172 patients with a mechanical prosthesis (53 CarboMedics and 119 Sorin Bicarbon) and in 106 patients with a bioprosthesis (15 St Jude Medical Toronto, 19 Baxter Perimount, and 72 Medtronic Mosaic) in the aortic position, mitral position, or both. Aortic valve replacement was performed in 206 patients, mitral valve replacement in 59 patients, and double valve replacement in 13 patients. The presence of hemolysis was assessed on the basis of the level of serum lactic dehydrogenase and serum haptoglobin and the presence and amount of reticulocytes and schistocytes in the peripheral blood. Severity of intravascular hemolysis was estimated on the basis of serum lactic dehydrogenase. Clinical, echocardiographic, and hematologic evaluations were performed 1, 6, and 12 months after discharge. RESULTS: None of the 278 patients experienced decompensated anemia, whereas at 12 months, mild subclinical hemolysis was identified in 49 patients, 44 (26%) with a mechanical prosthesis and 5 (5%) with a bioprosthesis (P <.001). At multivariate analysis, independent predictors of the presence of subclinical hemolysis were mitral valve replacement (P <.001), use of a mechanical prosthesis (P =.002), and double valve replacement (P =.02). Frequency of hemolysis in patients with stented aortic bioprostheses was 3%, whereas it was absent in those with stentless valves. Among mechanical valve recipients, double versus single valve replacement (P =.04) and mitral versus aortic valve replacement (P =.05) were correlated with the presence of hemolysis; double valve recipients also showed a more severe degree of hemolysis (P =.03). In patients with a Sorin Bicarbon prosthesis, hemolysis was less frequent (22% vs 34%, P =.09) and severe (P <.001) than in those with a CarboMedics prosthesis. CONCLUSIONS: In normally functioning prosthetic heart valves, subclinical hemolysis is a frequent finding. A low incidence of hemolysis is found in stented biologic prostheses, and it is absent in stentless aortic valves. Modifications of valve design may contribute to minimize the occurrence of hemolysis in mechanical prostheses.     

The pre-Vesalian kidney: Gabriele Zerbi, 1445-1505

Gabriel Zerbi was born in Verona in 1445 and died in Dalmatia in 1505. He was professor of philosophy in Padua at the age of 22, and moved to Bologna where he became professor of medicine and philosophy. In Rome at the time of Sixtus V and Innocentius VIII, he was archiater and professor of medicine. He completed his academic career in Padua where he worked from 1494 to 1505 with a salary of 600 florins a month. A man of vast culture, a philosopher, physician and professor of medicine, he wrote many books: (1) Questiones Metaphysicae; (2) Gerentocomia; (3) De Cautelis Medicorum; (4) Liber anatomiae corporis humani et singulorum membrorum illius; (5) De anatomia infantiis et porci ex traditione Cophonis, and (6) Libellus de preservatione corporum a passione calculosa. His contribution to anatomy was superb. Through him the discipline became the basis of modern medicine. The core of this article deals with some passages of Zerbi's chapters on the anatomy of the kidneys and bladder.     

Magnetization transfer can predict clinical evolution in patients with multiple sclerosis

The clinical course of multiple sclerosis (MS) is highly variable ranging from benign to aggressive, and is difficult to predict. Since magnetization transfer (MT) imaging can detect focal abnormalities in normal-appearing white matter (NAWM) before the appearance of lesions on conventional MRI, we hypothesized that changes in MT might be able to predict the clinical evolution of MS. We assessed MR data from MS patients who were subsequently followed clinically for 5 years. We computed the mean MT ratio (MTr) in gray matter, in lesions identified on T2-weighted MRI, and in NAWM, as well as in a thick central brain slice for each patient. Patients were divided into stable and worsening groups according to their change in Expanded Disability Status Scale (EDSS) scores over 5 years. We calculated the sensitivity, specificity, predictive value, and odds ratio of the baseline MTr measures in order to assess their prognostic utility. We found significant differences in baseline MTr values in NAWM (p = 0.005) and brain slice (p = 0.03) between clinically stable and worsening MS patients. When these MTr values were compared with changes in EDSS over 5 years, a strong correlation was found between the EDSS changes and MTr values in both NAWM (SRCC = −0.76, p < 0.001) and in the brain slice (SRCC = 0.59, p = 0.01). Baseline NAWM MTr correctly predicted clinical evolution in 15/18 patients (1 false positive and 2 false negatives), yielding a positive predictive value of 77.78 %, a negative predictive value of 88.89 %, and an odds ratio of 28. The relationship between 5-year changes in EDSS and MTr values in T2 weighted MRI lesions was weaker (SRCC = −0.43, p = 0.07). Our data support the notion that the quantification of MTr in the NAWM can predict the clinical evolution of MS. Lower MTr values predict poorer long-term clinical outcome. Abnormalities of MTr values in the NAWM are more relevant to the development of future patient disability than those in the T2-weighted MRI lesions. Received: 3 May 2001, Received in revised form: 11 October 2001, Accepted: 22 October 2001     

Multi-disciplinary clinical protocol for the diagnosis of bulbar amyotrophic lateral sclerosis

Introduction and objectives

The objective of this study was to examine the role of different specialists in the diagnosis of amyotrophic lateral sclerosis (ALS), to understand changes in verbal expression and phonation, respiratory dynamics and swallowing that occurred rapidly over a short period of time.

Decreased cerebrospinal fluid levels of neutral and basic amino acids in patients with Parkinson''s disease

We measured the CSF levels of 21, and the plasma levels of 26, amino acids in 31 patients with Parkinson's disease (PD) and in 45 matched controls. We used an ion-exchange chromatography method. When compared to controls, PD patients had lower CSF levels of taurine, alanine, valine, leucine, isoleucine, ethanolamine, citrulline, ornithine, lysine, histidine, arginine, and alpha-aminobutyric acid. PD patients not treated with levodopa or with dopamine agonists had higher CSF tyrosine and phenylalanine levels than those not treated with these drugs and also than controls. PD patients had higher plasma levels of phosphoserine, threonine, methionine, tyrosine, sarcosine and -aminoadipic acid, and lower plasma levels of valine, leucine, and tryptophan, than controls. The CSF/plasma ratio of many of these amino acids was significantly lower in PD patients than those of controls, suggesting that PD patients might have a dysfunction in the transport of neutral and basic amino acids across the blood–brain barrier.     

Stereologic study of Purkinje cells in mice after early exposure to phenobarbital

The present investigation was designed to study the dendritic tree of the Purkinje cells surviving after prenatal (Pre B) or neonatal (Neo B) exposure to phenobarbital (PhB). Prenatal exposure in mice was accomplished transplacentally by feeding the pregnant mother 3 g PhB/kg milled food on getation days 9 to 18. Neonatal exposure was conducted directly by injecting the neonates daily (50 mg PhB/kg) on postnatal days 2 to 21. Brains were removed at 14, 21, and 50 days of age. They were cut in the sagittal plane and prepared according to the Golgi method for analysis of the Purkinje cells dendrites. A few brains of 50-day-old Neo B and controls were cut and stained with hemotoxylin and eosin for the assessment of number of Purkinje cells. Neonatal PhB exposure caused 9% reduction in the number of dendritic spines per millimeter at age 14 and 21 days. This deficit was only transient as it disappeared by day 50. However, when the injection dose was reduced to 40 mg PhB/kg the deficits persisted to day 50. Possibly, selection against the most affected individuals accounted for the lesser effect of the higher dose. Prenatal PhB exposure had no long-lasting effect on the dendritic spines. No deficit in the area of the dendritic tree or the number of branches of all orders could be detected in any of the PhB-treated groups studied. Early PhB administration which had severe effects on the neuronal number, had a relatively small effect on the dendrites of the surviving Purkinje cells. Unlike some milder insults, it did not decrease the ratio of granule cells: Purkinje cells, and it is possible that the dendritic effects were dependent on changes in this ratio.