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Biomedical subjects

A Rossi

Publications and source records attributed to A Rossi.

At least 145 records · Page 8Linked to original sources

X-ray photoelectron spectra of Pd(II) and Pt(II) complexes with 1,3-thiazolidine-2-thione. A quantum mechanics study on the free ligand.

Metal complexes of general formula M(ttz)2X2 (with M= Pd(II) or Pt(II); X = Cl or Br; ttz = 1,3-thiazolidine-2-thione) have been synthetized as crystalline compounds and studied by means of X-ray Photoelectron Spectroscopy (XPS). The chemical shift of core level signals showed that ttz is bonded to the metal through the thioketonic sulphur atom and that electronic charge redistribution in the ligand takes place after complexation. No metal-nitrogen bonds are present. This is consistent with the results of all the quantum mechanical models according to which hydrogen is bound to nitrogen, even in the hydrogen bonded complex, making the latter rather unavailable to coordination

Ligands↗

Frequency, prognosis and predictors of improvement of systolic left ventricular function in patients with 'classical' clinical diagnosis of idiopathic dilated cardiomyopathy.

In patients with dilated cardiomyopathy (DCM) of different aetiologies, a variable frequency of improvement in the left ventricular (LV) systolic function has been reported, while in patients with a 'classic' idiopathic DCM, the frequency of improvement is still under debate, and clinical and haemodynamic predictors of recovery of the LV function are needed. The aim of the present study was to determine the frequency of improvement in the LV systolic function in idiopathic DCM and to identify predictors of reversibility of the impaired LV contractility. A sample of 98 consecutive patients with idiopathic DCM was retrospectively evaluated. Echocardiographic and Doppler measurements were directly taken from the routine echo-report. LV systolic function was assessed semiquantitatively using a score index (SFSI). According to the improvement in the LV systolic function, the patients were divided into group 1 patients with improvement, and group 2 patients without improvement. During a follow-up of at least 12 months, 19 patients (19%) showed an improvement, with a significant increase in the mean SFSI; all these group 1 patients survived without heart transplant; in group 2, 18 patients (23%) died and 3 (4%) received a heart transplant. Patients in group 1 had a significantly shorter duration of symptoms (P=0.0045), a younger age (P=0.006), a shorter DtE (P=0.04), a lower SFSI (P<0.01), a worse NYHA class (P<0.001) and more frequently had a history of hypertension (P<0.0001). The same variables were significant predictors of improvement at the univariate analysis. At the multivariate logistic regression analysis, a shorter duration of symptoms (P=0.02), a history of hypertension (P=0.003), and a worse NYHA class (P=0.01) were independent predictors of improvement. A relatively large percentage of patients with an idiopathic DCM will have a marked improvement in the LV systolic function. This is more likely to happen in the presence of a short duration of symptoms and a history of hypertension. After an improvement, the prognosis is excellent.

Adult↗

Distribution of [3H]GR65630 binding in human brain postmortem.

We investigated the distribution of serotonin (5-HT) receptors of type 3 (5-HT3) in human brain areas, by means of the the specific binding of [3H]GR65630. The brains were obtained during autoptic sessions from 6 subjects. Human brain membranes and the binding of [3H]GR65630 were carried out according to standardized methods. The highest density (Bmax +/- SD, fmol/mg protein) of [3H]GR65630 binding sites was found in area postrema (13.1+/-9.7), followed at a statistically lower level, by nucleus tractus solitarius (6.7+/-3.4), nervus vagus (5.5+/-2.1), striatum (4.8+/-2.4) with a progressive decrease in amygdala, olivar nuclei, hippocampus, olfactory bulbus and prefrontal cortex, and then by the other cortical areas and the cerebellum, where no binding was detected. These observations extend previous findings on the distribution of 5-HT3 receptors and confirm interspecies variations that might explain the heterogeneous properties of 5-HT3 receptors in different animals.

Aged↗

Phase I study of a weekly schedule of oxaliplatin, high-dose leucovorin, and infusional fluorouracil in pretreated patients with advanced colorectal cancer.

PURPOSE: To identify the maximum tolerated dose (MTD) and dose limiting toxicities (DLT) of oxaliplatin (L-OHP) given on a weekly schedule including fixed doses of leucovorin (LV) and infusional 5-fluorouracil (5-FU), to define the toxicity profile of this regimen and to find preliminary evidence of its activity in pretreated patients with metastatic colorectal cancer (MCRC). PATIENTS AND METHODS: Twenty-one patients with progressive disease, treated with fluoropyrimidines and with histologically measurable MCRC entered into this phase I study. Fixed doses of LV (500 mg/m2) followed by a 48-hour 5-FU 2600 mg/m2 infusion (5-FU48h) were administered with escalating doses of L-OHP, starting from 60 mg/m2 and with stepwise increments of 5 mg/m2. No intra-patient dose escalation was allowed. Treatment was given once a week for four consecutive weeks, followed by a one-week rest period. RESULTS: Three dose levels were tested. The MTD was L-OHP 70 mg/m2 since two of the three patients showed dose-limiting diarrhea and the third developed neutropenia during the first cycle of chemotherapy. Most patients complained of mild peripheral sensitive neurotoxicity, which was related to the cumulative dose of L-OHP. Treatment delays were necessary for a total of 42 cases, but only in II of 42 after the pre-arranged 10% dose reduction of 5-FU (2300 mg/m2). Sixteen patients were evaluable for response: seven (33%; 95% confidence interval (CI): 14.6%-57.0%) were considered to show a major response (one complete), six showed a stable disease, and in addition progressive disease was observed in three patients. CONCLUSIONS: Our results show that L-OHP, LV and 5-FU can be administered safely and repetitively using a weekly schedule. Diarrhea and neutropenia are the DLT of this regimen. Its activity and its manageable toxicity profile deserve further evaluation in chemotherapy-naïve MCRC patients. The doses recommended for phase II trials are: L-OHP 65 mg/m2, LV 500 mg/m2 and 5-FU48h 2300 mg/m2 infusion given on a weekly-times-four schedule followed by a one-week rest period.

Aged↗

Bcl-2/Bax protein expression in heart, slow-twitch and fast-twitch muscles in young rats growing under chronic hypoxia conditions.

We have studied the magnitude of apoptosis in heart, slow-twitch skeletal muscle (soleus) and fast-twitch skeletal muscle (gastrocnemius) of rats exposed to 3 weeks in vivo chronic hypoxia. Apoptosis was evaluated biochemically by DNA laddering and by TUNEL and annexin V-staining. The expression of Bax and Bcl-2 proteins was determined by immunohistochemistry and Western blotting. Western blot analysis revealed only a slight difference in Bax expression among the different tissues under normoxic and hypoxic conditions; therefore we can consider that Bax protein is constitutively expressed in muscle tissues. However a singular pattern of Bcl-2 expression was observed among the different tissues under normoxic conditions. Bcl-2 protein was more expressed in fast-twitch glycolytic muscles than in slow-twitch or oxidative muscles with a highest value found in gastrocnemius (4926 +/- 280 AU), followed by soleus (2138 +/- 200 AU) and a very low expression was displayed in the heart muscle (543 +/- 50 AU). After exposure to hypoxia for 21 days (10% O2), Bcl-2 protein expression markedly increased, (44%) in gastrocnemius, (323%) in soleus and (1178%) in heart, with significant differences (p < 0.05 student t-test), reaching a similar threshold of expression in both types of muscles. Furthermore, no sign of apoptosis was detected by TUNEL assay, annexin V-binding assay or DNA electrophoresis analysis. The latter suggested some indiscriminate fragmentations of DNA without apoptosis. In conclusion, we postulate that these protein modifications could represent a adaptative mechanism allowing a better protection against the lack of oxygen in oxidative muscles by preventing apoptosis.

Animals↗

Intensification of salvage treatment with high-dose sequential chemotherapy improves the outcome of patients with refractory or relapsed aggressive non-Hodgkin's lymphoma.

The aim of the present study was to retrospectively evaluate whether a high-dose sequential chemotherapy programme (HDS: cyclophosphamide, methotrexate, etoposide) administered prior to autologous transplantation could optimize the salvage of patients with refractory or relapsed aggressive non-Hodgkin's lymphoma. Between 1985 and 1999, 103 patients (median age 43 years, range 16-65) from eight Italian centres and one Swiss centre, with refractory (n = 38) or relapsed (n = 65) diffuse large B-cell and T-cell lymphoma, were treated using HDS followed by high-dose regimens with autologous haematopoietic stem cell transplantation. Eighty-three patients responded to the HDS regimen (81%, 95% C.I., 73- 88%) and 79 eventually achieved a complete response (CR) after autotransplantation (90%, 95% C.I., 81- 96%). None of 20 cases resistant to HDS attained CR. Treatment-related mortality was 4%. After a median follow-up of 24 months (range 6-174 months), 3-year estimates of overall survival, event-free survival and disease-free survival were 47% (95% C.I., 36-59%), 44% (95% C.I., 34-54%) and 64% (95% C.I., 50-74%) respectively. Multivariate analysis showed that chemosensitivity to HDS represented the strongest predictor of both CR and survival. This retrospective study shows that salvage treatment using HDS had relatively low toxicity and was associated with remarkable response rates, allowing further effective therapy with high-dose autograft programmes.

Adolescent↗

A nucleotide insertion and frameshift cause albumin Kénitra, an extended and O-glycosylated mutant of human serum albumin with two additional disulfide bridges.

Albumin Kenitra is a new type of genetic variant of human serum albumin that has been found in two members of a family of Sephardic Jews from Kenitra (Morocco). The slow-migrating variant and the normal protein were isolated by anion-exchange chromatography and, after treatment with CNBr, the digests were analyzed by two-dimensional electrophoresis in a polyacrylamide gel. The CNBr peptides of the variant were purified by reverse-phase high performance liquid chromatography and submitted to sequence analysis. Albumin Kenitra is peculiar because it has an elongated polypeptide chain, 601 residues instead of 585, and its sequence is modified beginning from residue 575. DNA structural studies showed that the variant is caused by a single-base insertion, an adenine at nucleotide position 15 970 in the genomic sequence, which leads to a frameshift with the subsequent translation to the first termination codon of exon 15. Mass spectrometric analyses revealed that the four additional cysteine residues of the variant form two new S-S bridges and showed that albumin Kenitra is partially O-glycosylated by a monosialylated HexHexNAc structure. This oligosaccharide chain has been located to Thr596 by amino-acid sequence analysis of the tryptic fragment 592-597.

Adenine↗

Additional value of pulmonary vein parameters in defining pseudonormalization of mitral inflow pattern.

BACKGROUND: An echocardiographic assessment of left ventricular (LV) diastolic dysfunction is still challenging when identifying a pseudonormal mitral pattern (PSE) in an unselected population. The present study analyzed and compared the accuracy of various parameters in correctly identifying a PSE pattern in patients with a broad range of ejection fraction (EF) and degree of mitral regurgitation. METHODS: Eighty-two patients with E/A > or = 1 and an invasive determination of left ventricular end-diastolic pressure (LVEDP) were enrolled in the study. Mitral E wave (E(max)) and A (A(max)) velocities, E (DTe) and A (DTa) deceleration times, pulmonary vein systolic and diastolic velocities, and time velocity integrals were measured. The different duration between mitral and pulmonary vein A wave (A'-A) also was calculated. E(max) and E/A during Valsalva maneuver were measured and expressed as percentage compared with baseline. LV end-diastolic (LVD), end-systolic (LVS), and EF were measured from the apical four-chambers view (area-length method). Left atrial end-systolic (LA(max)) and end-diastolic (LA(min)) were measured from the apical four- and two-chambers views (area-length method). Left atrial filling volume (LA(fill)) was the difference between LA(max) and LA(min). Mitral regurgitant volume was estimated by the following equation: MR(vol) = 6.18 + (1.01 * LA(fill)) - (0.783 * PVs %). RESULTS: Thirty-two patients (age: 55 +/- 21 years; 75% male) had LVEDP < or = 18 mmHg and were classified as normal mitral pattern (Group 1). Fifty patients (age: 57 +/- 22 years; 76% male) had LVEDP > 18 mmHg, and were classified accordingly as having PSE (Group 2). At logistic univariate analysis, DTa (0.005), LV EF (0.01), A'-A (< 0.0001) and % E/A (0.03) were the more powerful predictors of PSE. A'-A had the highest global accuracy in identifying PSE in patients with reduced (90%) and normal (88%) LV EF. CONCLUSION: A'-A has the highest accuracy in identifying PSE in an unselected population. This parameters should be implemented in routine echocardiography since it allows additional information about LV diastolic function assessment.

Blood Flow Velocity↗

Cobalamin (Cbl) C/D deficiency: clinical, neurophysiological and neuroradiologic findings in 14 cases.

The early onset type of cobalamin (Cbl) C/D deficiency is characterised by feeding difficulties, failure to thrive, hypotonia, seizures, microcephaly and developmental delay. It has an unfavourable outcome, often with early death and significant neurological impairment in survivors. While clinical and biochemical features of Cbl C/D deficiency are well known, only a few isolated case reports are available concerning neurophysiological and neuroimaging findings. We carried out clinical, biochemical, neurophysiological and neuroradiologic investigations in 14 cases with early-onset of the Cbl CID defect. Mental retardation was identified in most of the cases. A variable degree of supratentorial white matter atrophy was detected in 11 cases by MR imaging and tetraventricular hydrocephalus was present in the remaining 3 patients. Waking EEG showed a clear prevalence of epileptiform abnormalities, possibly related to the high incidence of seizures in these cases. Increased latency of evoked responses and/or prolongation of central conduction time were the most significant neurophysiological abnormalities. The selective white matter involvement, shown both by neuroradiologic and neurophysiological studies, seems to be the most consistent finding of Cbl C/D deficiency and may be related to a reduced supply of methyl groups, possibly caused by the dysfunction in the methyl-transfer pathway.

5-Methyltetrahydrofolate-Homocysteine S-Methyltran↗

Mitral regurgitation and left ventricular diastolic dysfunction similarly affect mitral and pulmonary vein flow Doppler parameters: the advantage of end-diastolic markers.

Enhanced early mitral flow and reduced systolic pulmonary vein flow may be caused both by increased left ventricular pressure as the result of diastolic dysfunction and by increased transmitral flow as the result of mitral regurgitation. Nevertheless, Doppler parameters are widely used to predict left ventricular filling pressure. We aimed to analyze the interference of mitral regurgitation with Doppler parameters usually used to estimate left ventricular filling pressure and to identify markers independent of mitral regurgitation, which could reliably estimate increased left ventricular filling pressure. Eighty-four patients (age, 62 +/- 9 years; 82% men) had a complete echocardiographic Doppler examination. Transmitral E- and A-wave velocity, E deceleration time and A duration, pulmonary vein systolic and diastolic velocities, and reversal flow duration and maximal and minimal left atrial volumes were measured. The difference between the duration of pulmonary vein and mitral A waves was calculated (A'-A). Mitral regurgitant volume was quantitatively assessed by echocardiography. Left ventricular end-diastolic pressure was measured invasively. Patients had a wide range of left ventricular ejection fraction (14% to 70%), mitral regurgitant volume (0 to 94 mL), and left ventricular end-diastolic pressure (3 to 37 mm Hg). E velocity, E/A, pulmonary vein systolic and diastolic, and systo-diastolic ratios were significantly and independently correlated with both left ventricular end-diastolic pressure and mitral regurgitant volume. A'-A showed a strong correlation with left ventricular end-diastolic pressure (r = 0.70; P <.0001), but the relation with mitral regurgitant volume was not significant (r = 0.19; P =.08). Mitral regurgitation affects the majority of Doppler parameters widely used to predict filling pressure but does not influence Ad'-Ad, which proved to be the strongest predictor of left ventricular end-diastolic pressure.

Aged↗

Quality of life in elderly cancer patients.

Increasing age is a major risk factor for developing cancer and the number of older people is rapidly expanding. Therefore, cancer in the geriatric population is becoming an emerging problem. Older patients are extremely heterogeneous. Instruments collecting information related to comorbidity and disability, (which have both been demonstrated to affect the survival of elderly patients) may help treatment decision. The G.I.O.Ger (Gruppo Italiano di Oncologia Geriatrica) has validated a Comprehensive Geriatric Assessment (CGA) scale for geriatric cancer patients, and we recommend its use in clinical practice. Our findings suggest that cancer adversely affects physical performance and psychological status less than other comorbidities. Many aspects of physical limitations are not totally recognised by performance status, in particular those aspects of daily life that require instrumental activities and that may affect adherence to diagnostic or therapeutic protocols. Quality of life as a main objective in the management of elderly cancer patients is now recognized by many clinicians. In clinical practice. quality of life means maintenance of function and symptom control, and quality-of-life instruments rated by the patient rather than by clinicians should be preferred. Whether it is preferable to use cancer-specific or generic instruments is an ongoing debate.

Aged↗

Magnetic resonance imaging of spinal dysraphism.

Spinal cord development occurs through three consecutive periods. Gastrulation (weeks 2-3) is characterized by conversion of the embryonic disk from a bilaminar to a trilaminar arrangement and establishment of a notochord. Primary neurulation (weeks 3-4) produces the uppermost nine tenths of the spinal cord. Secondary neurulation and retrogressive differentiation (weeks 5-6) result in formation of the conus tip and filum terminale. Defects in these early embryonic stages produce spinal dysraphisms, which are characterized by anomalous differentiation and fusion of dorsal midline structures. Spinal dysraphisms may be categorized clinically into two subsets. In open spinal dysraphisms, the placode (non-neurulated neural tissue) is exposed to the environment. These disorders include myelomeningocele, myeloschisis, hemimyelomeningocele, and hemimyelocele, and are always associated with a Chiari II malformation. Closed spinal dysraphisms are covered by intact skin, although cutaneous stigmata usually indicate their presence. Two subsets may be identified based on whether a subcutaneous mass is present in the low back. Closed spinal dysraphisms with mass comprise lipomyeloschisis, lipomyelomeningocele, meningocele, and myelocystocele. Closed spinal dysraphisms without mass comprise complex dysraphic states (ranging from complete dorsal enteric fistula to neurenteric cysts, split cord malformations, dermal sinuses, caudal regression, and spinal segmental dysgenesis), bony spina bifida, tight filum terminale, filar and intradural lipomas, and persistent terminal ventricle. Magnetic resonance imaging is the imaging method of choice for investigation of this complex group of disorders.

Adolescent↗

Clinical relevance of monitoring respiratory mechanics in the ventilator-supported patient: an update (1995-2000).

The introduction of mechanical ventilation in the intensive care unit environment had the merit of putting a potent life-saving tool in the physicians' hands in a number of situations; however, like most sophisticated technologies, it can cause severe side effects and eventually increase mortality if improperly applied. Assessment of respiratory mechanics serves as an aid in understanding the patient-ventilator interactions with the aim to obtain a better performance of the existing ventilator modalities. It has also provided a better understanding of patients' pathophysiology. Thanks to it, new ventilatory strategies and modalities have been developed. Finally, on-line monitoring of respiratory mechanics parameters is going to be more than a future perspective.

Adult↗

PCR-hybridization assay for Mycobacterium avium complex: optimization of detection in peripheral blood from humans.

We evaluated the sensitivity of a DNA amplification test for the detection of Mycobacterium avium in blood samples using different blood components and different DNA extraction methods. M. avium-inoculated blood samples were processed to obtain separate blood components: peripheral blood mononuclear cells (PBMCs), polymorphonuclear cells (PMNCs), and whole-blood sodium dodecyl sulfate (SDS)-lysate pellets. The sensitivity for the detection of the lowest mycobacterial load (1 CFU/ml) was significantly greater (P < 0.01) with DNA extracted from SDS-lysate pellets than with DNA extracted from PBMCs or PMNCs. Subsequently, DNA extraction methods based on guanidine NaOH, and proteinase were compared. The sensitivity of the guanidine-based method was significantly greater (P < 0.01) than those of the others.

Bacteremia↗

Three-year assessment of methicillin-resistant Staphylococcus aureus clones in Latin America from 1996 to 1998.

Four hundred ninety-nine methicillin-resistant Staphylococcus aureus (MRSA) isolates recovered from 1996 to 1998 from 22 hospitals in five countries of Latin America-Argentina, Brazil, Chile, Uruguay and Mexico-were examined for antimicrobial susceptibility and clonal type in order to define the endemic clones in those hospitals. The hybridization of ClaI restriction digests with the mecA- and Tn554-specific DNA probes combined with pulsed-field gel electrophoresis of chromosomal SmaI digests (ClaI-mecA::ClaI-Tn554::PFGE clonal types) documented not only the predominance and persistence of the Brazilian clone (XI::B::B) in Brazil (97%) and Argentina (86%) but also its massive dissemination to Uruguay (100%). Moreover, a close relative of the Brazilian clone (XI::kappa::B) was highly represented in Chile (53%) together with a novel clone (47%) (II::E'::F) resistant to pencillin, oxacillin, ciprofloxacin, chloramphenicol, clindamycin, erythromycin, and gentamicin. A unique clonal type (I::NH::M) was detected in Mexico among pediatric isolates and was resistant to penicillin, oxacillin, and gentamicin only. This study clearly documented the very large capacity for geographic expansion and the persistence of the Brazilian clone, contributing not only to the increasing uniformity of the MRSA in South America but worldwide as well.

Anti-Bacterial Agents↗

Lower inflection point and recruitment with PEEP in ventilated patients with acute respiratory failure.

The lower inflection point (LIP) on the total respiratory system pressure-volume (P-V) curve is widely used to set positive end-expiratory pressure (PEEP) in patients with acute respiratory failure (ARF) on the assumption that LIP represents alveolar recruitment. The aims of this work were to study the relationship between LIP and recruited volume (RV) and to propose a simple method to quantify the RV. In 23 patients with ARF, respiratory system P-V curves were obtained by means of both constant-flow and rapid occlusion technique at four different levels of PEEP and were superimposed on the same P-V plot. The RV was measured as the volume difference at a pressure of 20 cm H(2)O. A third measurement of the RV was done by comparing the exhaled volumes after the same distending pressure of 20 cm H(2)O was applied (equal pressure method). RV increased with PEEP (P < 0.0001); the equal pressure method compares favorably with the other methods (P = 0.0001 by correlation), although individual data cannot be superimposed. No significant difference was found when RV was compared with PEEP in the group of patients with a LIP < or =5 cm H(2)O and the group with a LIP >5 cm H(2)O (76.9 +/- 94.3 vs. 61.2 +/- 51.3, 267.7 +/- 109.9 vs. 209.6 +/- 73.9, and 428.2 +/- 216.3 vs. 375.8 +/- 145.3 ml with PEEP of 5, 10, and 15 cm H(2)O, respectively). A RV was found even when a LIP was not present. We conclude that the recruitment phenomenon is not closely related to the presence of a LIP and that a simple method can be used to measure RV.

Acute Disease↗