[Evaluation of the withdrawal of ACE inhibitors in coronary artery surgery]. / Valutazione della sospensione degli ACE-inibitori in chirurgia cardiaca coronarica.

During cardiac surgery, as a result of surgical aggression, myocardial ischaemia and cardiopulmonary bypass, the renin-angiotensin-aldosterone mechanism is intensely activated. Our aim is to document whether, in the case of patients undergoing chronic treatment with lisinopril, the non-withdrawal of this inhibitor's administration before cardiac surgery and the administering of a last dose on the day of the operation are associated with coronary haemodynamic alterations. A study was made of 18 patients submitted to myocardial revascularization under extracorporeal circulation and distributed in two groups: group A) without ACE inhibitorsplacebo, group B) with ACE inhibitors (Lisinopril). Coronary blood flow (CBF) was determined by inverted thermodilution via Baim's catheter. Coronary and metabolic haemodynamic values were calculated. Lisinopril had no significant influence on the CBF or on the other above-mentioned values. Therefore, it is not necessary to withdraw ACE inhibitors in cardiac surgery interventions.

Apoptotic cell death and genetic control in graft coronary artery disease in heart transplant.

AIM: Apoptosis is a type of programmed cell death whereby, immunologic, genetic and biochemical mechanisms are involved in its control. On the other hand, graft coronary artery disease is the most important restrictive factor for the long-term survival of heart transplantation. The purpose of this study is to analyse both apoptotic cell lesions in transplanted patients that present coronary artery disease. METHODS: From August 1984 until December 1996, 148 heart transplants were carried out in the Clínica Universitaria de Navarra. In 102 patients, annual coronary angiography was performed, reaching a diagnosis of coronary artery disease in 30 patients. Study of apoptotic cell death was done in the tissue of endomyocardial biopsies on all patients by means of the TUNEL technique. Procedures of immunohistochemistry with antibodies antic-myc, p53 and bcl-2 were carried out and results were compared with a control group of 30 patients with homogeneous characteristics. RESULTS: All patients with coronary artery disease showed apoptotic cardiomyocytes, 13 patients to a mild degree, 14 to a moderate degree and 3 to a severe degree, while in the control group apoptosis was found only to a mild degree in 8 patients, obtaining a very significant statistical difference (p<0.0001). The expression of analysed oncoproteins was null in the 2 groups. CONCLUSION: Myocardial apoptosis is a constant finding in transplanted patients with coronary artery disease. We have not seen any correlation between the apoptotic process and genetic mechanisms.

Production of antibodies and development of highly sensitive formats of enzyme immunoassay for saxitoxin analysis.

In this paper the production of antibodies against saxitoxin (STX) is described, as is the optimization and comparison of two competitive ELISA formats (direct and indirect) for the detection of this toxin. Tests were performed in a 96-well microplate using the toxin-specific polyclonal antibodies produced in our laboratory, obtained from rabbits immunized with saxitoxin-keyhole limpet hemocyanin (STX-KLH). In indirect ELISA format saxitoxin, conjugated to bovine serum albumin (STX-BSA) was coated onto the microtitre plate and incubated with standard toxin and anti-STX antibody. A goat anti-rabbit IgG Peroxidase conjugate was used to enable detection. In the direct ELISA format, STX standard, STX conjugate to horseradish peroxidase (STX-HRP), and enzyme substrate/chromogen solution were sequentially added to the microplate after antibody coating.Results showed the saxitoxin detection limit to be 3 and 10 pg mL(-1) for direct and indirect ELISA formats, respectively. The suitability of the assay for quantification of saxitoxin in mussels was also studied. Samples were spiked with saxitoxin before and after sample treatment to study the extraction efficiency and matrix effect, respectively. After treatment, samples were analysed at 1:1000 v/v dilution in PBS to minimize the matrix effect and to detect the regulatory limit of 40-80 micro g saxitoxin per 100 g mussels as stipulated by the Food and Drug Administration. The efficiency of extraction of saxitoxin was from 72 to 102%. These data were confirmed by liquid chromatography coupled with fluorimetric detection, the technique currently used for quantitative determination of toxins in seafood.

Immunodetection of lactosylated proteins as a useful tool to determine heat treatment in milk samples.

This paper reports the optimisation of a competitive immunoassay (ELISA) to detect lactosylated proteins in milk samples. The assay employs monoclonal antibodies for lactosylated proteins produced in our laboratory and requires no pre-treatment of the samples other than a dilution step. Monoclonal antibodies were fully characterised in terms of selectivity and cross-reactivity with structurally related molecules and used in a competitive assay format with lactosylated standard proteins (lactosylated ovalbumin). The detection limit for lactosylated ovalbumin was 0.015 microgram ml-1 and the working range was from 0.010 to 40 micrograms ml-1. The data obtained indicate that the ELISA developed is applicable to diluted milk samples and is able to distinguish between milk samples that have undergone different heat treatments (UHT and pasteurised milk).

Plasma levels of amyloid beta 40 and 42 are independent from ApoE genotype and mental retardation in Down syndrome.

In Down syndrome (DS) brain an early, selective accumulation of amyloid beta (Abeta) peptides ending at residue 42 (Abeta42) occurs. Whether this event depends on an altered processing of amyloid beta precursor protein (APP) or on defective clearance is uncertain. To investigate this issue, we measured Abeta species 40 and 42 in plasma from 61 patients with DS, 77 age-matched normal controls, and 55 mentally retarded subjects without chromosomal abnormalities. The Abeta 40 and 42 plasma levels were then correlated with apolipoprotein E (apoE) genotypes in all groups of cases, and with I. Q. and Mini Mental Status Examination values in DS subjects. Both Abeta species were significantly elevated in DS compared to control groups, and the extent of their increase reflects that expected from APP gene overexpression. Plasma levels of Abeta 40 and 42 did not correlate with apoE genotypes in DS and control cases, and with the extent of mental retardation in DS subjects. The results indicate that accumulation and clearance of plasma and cerebral Abeta are regulated by different and independent factors.

Toward an artifical acetylcholinesterase.

The methanolysis of choline p-nitrophenylcarbonate in chloroform containing 1% methanol is catalyzed with turnover by ditopic receptors 1 and 2, consisting of a calix[6]arene connected to a bicyclic guanidinium by means of a short spacer. The calix[6]arene subunit strongly binds to the trimethylammonium head group through cation-pi interactions, whereas the guanidinium moiety is deputed to stabilize through hydrogen bonding reinforced by electrostatic attraction the anionic tetrahedral intermediate resulting from methoxide addition to the ester carbonyl. The observed cholinesterase activity had been anticipated on the basis of the ability of the ditopic receptors 1 and 2 to bind strongly to the choline phosphate DOPC, which is a transition state analogue for the BAc2-type cleavage of choline esters.

Phenylketonuria: diet for life or not?

In order to evaluate the argument whether or not a restricted phenylalanine diet should be maintained for life in patients with phenylketonuria (PKU), 16 patients with early treated PKU but off diet since their 11th birthday were investigated. The evaluation included a detailed neurological examination, IQ, neurophysiological testing and MRI of the brain. Even if IQ and electrophysiological studies were normal or unchanged if compared to results before diet discontinuation, all patients revealed abnormal neurological signs. We conclude that the diet should be continued during adult life, but somewhat higher phenylalanine levels (<10mg/dl;<600 micromol/l) than at younger ages should be allowed.

An unusual vascular graft infection by Aspergillus--a case report and literature review.

Vascular graft infection due to Aspergillus is a rare event. Only 11 previous case reports have been documented. All of these infections were in the aortic position, and infrainguinal arterial prosthetic graft involvement has been uncommon. The usual clinical presentation was back pain. Fever and systemic complaints were usually present. An unusual case that began with bilateral groin pain is reported and a review of the clinical presentation and the management of the other cases described in the literature is presented.

[Occult stromal tumour of the small intestine: a cause of chronic intestinal blood loss in a 70 year-old woman]. / Tumore stromale occulto del tenue causa di sanguinamento intestinale cronico in 70enne.

The case of a 70 year-old woman with a chronic gastrointestinal blood loss due to a stromal tumor located in the middle third of the small intestine is reported. The peculiarities of the case are the characteristic immunohistochemistry of the neoplasm and, particularly, the mimetic clinical presentation, a kind of ''phantom tumor'' confirmed only with celiotomy and surgical excision.

Alpha 6 beta 4 and alpha 6 beta 1 integrins associate with ErbB-2 in human carcinoma cell lines.

Growth factors modulate integrin-mediated cell adhesion and motility, and their receptors are thought to share proteins that mediate intracellular signaling with integrin receptors. The crosstalk between these receptors is thought to play a relevant role in transformation and tumor progression. To highlight possible interactions between growth factors and cell adhesion receptors we investigated whether integrins associate with tyrosine kinase receptors in tumor cells. By affinity chromatography and Western blot analyses of purified immune complexes, we studied the association of laminin receptors (alpha 6 beta 1 and alpha 6 beta 4) with ErbB-2 tyrosine kinase in human carcinoma cell lines. We demonstrated that the alpha 6 beta 4 and alpha 6 beta 1 integrins coprecipitated with ErbB-2 in lysates from carcinoma or NIH3T3 cells overexpressing ErbB-2. Integrin-mediated activation of ErbB-2 receptors suggested that this association is functionally meaningful. Indeed, carcinoma cells treated with a monoclonal antibody to the alpha 6 integrin subunit showed a ligand-dependent increase of ErbB-2-phosphorylated molecules coprecipitated with integrins and an increased DNA synthesis. The interaction between growth factor receptors and integrins was also studied in NIH3T3 cells overexpressing alpha 6 beta 4 receptors and ErbB-2 protein. We report that cells overexpressing both receptors, but not those overexpressing a crippled ErbB-2, showed enhanced proliferation rates and invasiveness, further suggesting that alpha 6 beta 4 integrin and ErbB-2 receptor interaction might contribute to generate a more malignant phenotype in carcinoma cells.

[Pericardial hematoma 2 years after coronary surgery]. / Hematoma pericárdico dos años después de cirugía coronaria.

Cardiac tamponade is a life-threatening complication after cardiac surgery which may develop in the early or late postoperative period. The latest have been defined arbitrarily as the ones occurring after the 7th postoperative day. They are less common than the early ones and most of the cases have been reported up to six months after the operation. They usually determine diagnostic difficulties that can negatively influence the prognosis. Because of its atypical late appearance, a case of a 65 year old man is presented who developed a postpericardiotomy syndrome and subsequently a pericardial clot nearly two years after aortocoronary bypass grafting.

Cognitive and affective assessment and multiple pathologies in institutionalized elderly.

Studies were carried out using the mini mental state examination (MMSE) and the geriatric depression scale (GDS) in 71 elderly patients, in order to establish eventual correlations between cognitive deficit, depression and multiple pathologies. This examination was part of a multidimensional evaluation involving patients over 65 years of age hospitalized in the Department of Clinical Medicine. The patients were divided into 5 grades on the basis of the extent ot functional impairments (from Grade 0 to Grade IV) (British Columbia Classification). Mean MMSE and GDS scores, as well as the mean of the multiple pathologies were calculated in each group. As all the MMSE items could not always be applied, we used a score obtained by dividing the maximum score accomplished by the maximum score applicable. No MMSb impairment was present in 94.11% of the Grade 0 patients, in 57.14% of the Grade I, in 37.5% of the Grade II, and in 40% of the Grade III patients. However, impairment was present in all the Grade IV patients. GDS analysis revealed no depression in 82.35% of Grade 0 patients, in 21.43% Grade I, in 50% Grade II, in 16% Grade III patients. However, some degree of depression was present in all Grade IV patients. The occurrence of patients affected by multiple pathologies was as follows: 1-2 pathologies were recorded in 47.06% of Grade 0 patients, in 57.14% Grade I, in 37.5% Grade II, in 36% Grade III, and in 57.14% of Grade IV patients.

Multiple pathologies and drug consumption in a group of centenarians from Eastern Sicily.

Multiple pathologies are characteristic for the elderly. We evaluated the prevalence of multiple pathologies in 28 randomly selected centenarians living in Eastern Sicily and compared the data with those obtained in another random group of 28 control subjects over 80 years of age. It has been revealed that 25% of the centenarians suffered from 0-3 pathologies, while the remaining 75% displayed more than 3 pathologies. The control subjects had 0-3 pathologies in 50% of over 80 years, while 50% were affected by more than 3 pathologies. In centenarians the most prevalent pathologies involved the sensorial apparatus (sight and hearing), followed by the digestive, urogenital and cardiovascular systems. In the control group the rank of occurrence was as follows: cardiovascular system, osteoarticular and respiratory apparatuses, and sensorium. We compared drug consumption in the two age groups. In the centenarians, 71.43% took 0-3 drugs, while 28.57% took more than 3 drugs. In the control group, 53.57% took 0-3 drugs, whereas 46.43% took more than 3 drugs.

Functional evaluation of a group of centenarians in Eastern Sicily by means of the activity of daily living scale.

A random sample of 28 centenarians was studied (32.56% of all centenarians in Eastern Sicily) within the framework of the Italian Multicenter Study on Centenarians. The activity of daily living (ADL) scale was applied to evaluate their capacity to perform everyday tasks autonomously. The study sample consisted of 8 males (28.57%) and 20 females (71.43%), overall mean age was 102.57 +/- 2.1 years. The patients fell into 3 groups according to their ADL scores independent group (with score A) 5 persons, 17.86% (2 males and 3 females); partially independent group (with scores B and C) 5 persons, 17.86% (1 male and 4 females); dependent group (with scores D-E-F-G and other) 18 persons, 64.29% (5 males and 13 females). We compared the results with a control study sample of 28 elderly patients (8 males, 20 females) over 85 years of age resident in a small village in Eastern Sicily (Graniti) and observed that the centenarians presented greater independence, especially the women.

Laboratory blood parameters in a group of centenarians.

Several laboratory blood parameters in a group of healthy centenarians (7 males and 15 females) living in Eastern Sicily were studied and compared with those recorded in a group of healthy elderly subjects (5 males and 12 females) from 80 to 87 years of age. Almost all the laboratory test parameters analyzed were within the range considered to be normal for adult subjects. The exceptions were some renal function markers such as azotemia and creatinine, which were higher in the centenarians, and total cholesterol levels, which were significantly lower in the male centenarians as compared to the elderly male subjects. The conclusion is drawn, therefore, that laboratory tests reflect the health conditions rather than the age of an individual.

Sense of smell in centenarians from Eastern Sicily.

The sense of smell was studied in a group of centenarians from Eastern Sicily, displaying a mini mental state examination score larger than 19. Analysis of the data demonstrated that centenarians retain the capacity to perceive olfactory stimuli. However, as compared to the results obtained in groups of young and elderly subjects, a statistically significant quantitative reduction (p < 0.001) in the sense of smell was revealed in the centenarians.