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Biomedical subjects

G Paone

Publications and source records attributed to G Paone.

At least 37 records · Page 2Linked to original sources

Quality of history taking in patients with aortic dissection.

STUDY OBJECTIVES: Aortic dissection generally is an acute catastrophe. Rapid diagnosis is critical. We hypothesized that the quality of history taking contributes to the accuracy of diagnosis in patients with dissection. DESIGN: Retrospective chart review of 83 patients, whose diagnosis of aortic dissection was confirmed by autopsy, surgery, CT scan, echocardiogram, or angiogram. The quality of the initial history was reviewed using predetermined criteria. The physicians' initial clinical impressions were recorded. RESULTS: The examining physician correctly suspected aortic dissection after the initial clinical evaluation in 54 of 83 patients (65%). Only 33 of 78 patients with symptoms (42%) were asked about the quality, location, and onset of their pain, the three descriptors identified a priori as important. In 19 patients (24%), only zero or one descriptor was recorded. When all three questions were asked, dissection was suspected in 30 of 33 patients (91%); when zero, one, or two questions were asked, dissection was suspected in 22 of 45 patients (49%). CONCLUSION: Despite important advances in diagnostic imaging, accurate diagnosis of aortic dissection requires an accurate history. In our series, the quality of initial history was associated with the accuracy of the initial clinical impression in patients with aortic dissection.

Aortic Dissection↗

The paradox of on-bypass transfusion thresholds in blood conservation.

BACKGROUND: While most reports on blood conservation define a specific transfusion trigger, few have primarily focused on the role of the predefined transfusion threshold in initiating blood utilization. This study was undertaken to test the hypothesis that rigid adherence to an arbitrarily defined protocol paradoxically increases homologous blood usage during isolated primary coronary artery bypass graft. METHODS AND RESULTS: Prospectively, 100 consecutive patients were transfused on bypass solely for low venous oxygen saturation (SvO2), ie, <55%, without regard to hematocrit (Hct), postoperative for Hct <20, or if clinically warranted. During bypass the lowest Hct value was <25% in 72 patients, <22% in 52 patients, <20% in 39 patients, <18% in 23 patients, and <15% in 2 patients. These data, then, represent the percentage of patients who would have received blood on bypass had each respective level been used as a trigger, and hence the minimum number of patients who would have been transfused overall. In this study only 13 patients received 2.2+/-0.3 U of red blood cells; 4 on bypass, 5 in the intensive care unit within 24 hours, and 4 on postoperative days 2 or 3. Of the 87 patients not transfused, 15 arrived in the intensive care unit with Hct <25%, 4 with Hct <22%. By postoperative day 1, there were 7 patients with Hct <25% and only 1 <22%, confirming that many of these patients would have been unnecessarily transfused had we adhered to any of the noted on-bypass transfusion triggers. There were no deaths, no strokes, one Q wave myocardial infarction, and one sternal infection. Postoperative blood loss and discharge Hct were 741+/-131 mL and 29.3+/-0.5 versus 573+/-27 mL and 29.1+/-1.0 in transfused and nontransfused patients (P=.24 and P=.88, respectively). CONCLUSION: These data suggest that avoiding use of a numerical on-bypass hematocrit trigger is safe and extremely effective in minimizing the use of homologous blood during isolated primary coronary artery bypass graft. Conversely, unless the chosen level is sufficiently low, ie, <15, setting arbitrary thresholds will paradoxically increase homologous blood utilization; data are mean+/-SEM.

Aged↗

Evaluation of response to chemotherapy in patients affected with non-small cell lung cancer by means of three tumour markers elaborated by discriminant analysis.

Chemotherapy is the most effective treatment for inoperable patients (70%) affected with non-small cell lung cancer (NSCLC). The early detection of tumour progression is mandative in order to promptly shift these patients towards salvage or supportive therapy. The present authors investigated the clinical value of a panel of tumour markers, elaborated by means of discriminant analysis, as a follow-up indicator for the detection of tumour progression. The serum levels of tissue polypeptide antigen (TPA), CYFRA-21.1, neuron-specific enolase (NSE) and carcino-embryonic antigen (CEA) were determined before chemotherapy and after three cycles of treatment. Discriminant analysis generated a formula (canonic variable) which correctly classified the 87.8% of the 74 subjects (86.1% of the 36 progressive diseases and 89.5% of 38 non-progressive diseases). This approach produces an algorithm able to calculate a progression score in NSCLC patients which can be helpful for following-up care and therapy control of these patients.

Adult↗

Validation of an algorithm able to differentiate small-cell lung cancer (SCLC) from non-small-cell lung cancer (NSCLC) patients by means of a tumour marker panel: analysis of the errors.

By means of a mathematical score previously generated by discriminant analysis on 90 lung cancer patients, a new and larger group of 261 subjects [209 with non-small-cell lung cancer (NSCLC) and 52 with small-cell lung cancer (SCLC)] was analysed to confirm the ability of the method to distinguish between these two types of cancers. The score, which included the serum neuron-specific enolase (NSE) and CYFRA-21.1 levels, permitted correct classification of 93% of the patients. When the misclassifications were analysed in detail, the most frequent errors were associated with limited disease SCLC with low NSE levels and with advanced NSCLC with high NSE levels. This demonstrates the importance of the marker in correctly categorizing patients.

Adult↗

Carcinoembryonic antigen, tissue polypeptide antigen and neuron-specific enolase pleural levels used to classify small-cell and non-small-cell lung cancer patients by discriminant analysis.

The classification of lung cancer into small-cell lung cancer (SCLC) and non-small-cell lung cancer (NSCLC) is essential for disease prognosis and treatment. For this purpose, we have tried to optimize the use of three tumour markers determined on pleural effusions, to differentiate SCLC from NSCLC by means of a canonic variable, generated by discriminant analysis, including subjects with histologically proven lung cancer. Discriminant analysis was performed by using carcinoembryonic antigen, neuron-specific enolase and tissue polypeptide antigen pleural levels, determined in 65 consecutive and unselected patients, histologically classified as 49 NSCLC and 16 SCLC. To validate the formula generated, a control group of 37 lung cancer patients (10 SCLC and 27 NSCLC), enrolled subsequently, was employed. Applying the discriminant analysis to SCLC and NSCLC patients a good classification was obtained (92% rate of correct classification). The aforementioned formula, applied to the validation group, showed a 92% rate of correct classification. This method, which is rapid, inexpensive and routinely applicable to malignant pleural effusions, may be reliably used to classify lung cancer patients.

Adult↗

The immune response to mycobacterial 70-kDa heat shock proteins frequently involves autoreactive T cells and is quantitatively disregulated in multiple sclerosis.

Heat shock proteins (HSP) are the most conserved molecules known to date that may also function as immune targets during infection. Hence, theoretically there is a high chance of cross-reactive responses to epitopes shared by host and microbe HSP. If not properly regulated, these responses may contribute to the pathogenesis of autoimmune disease. To determine if immune responses to HSP could contribute to the pathogenesis of multiple sclerosis, we raised T lymphocyte lines specific for the purified protein derivative of Mycobacterium tuberculosis (PPD) from patients with multiple sclerosis, patients with tuberculosis and from healthy individuals. These lines were then screened for their proliferative response to a M. tuberculosis 70-kDa heat shock protein (M.tb.HSP70). The relative frequency of the recognition of highly conserved sequences of M.tb.HSP70 compared to variable ones was also assessed by mapping experiments on those PPD specific T lymphocyte lines which also recognized the mycobacterial 70-kDa heat shock protein. In patients with multiple sclerosis, we observed a significantly higher estimated frequency of PPD-specific T lines responding to M.tb.HSP70 compared to healthy individuals and patients with tuberculosis. Furthermore, mapping experiments using recombinant proteins representing mycobacterial and human HSP70 sequences and a panel of synthetic peptides encompassing the whole sequence of Mycobacterium leprae HSP70, showed that the response to conserved epitopes of HSP70 is a frequent event in each of the three conditions studied, often leading to the cross-recognition of microbial and human sequences. These findings implicate the 70-kDa heat shock proteins as potential autoantigens in multiple sclerosis.

Adult↗

Expression of lysosomal acid lipase mutants detected in three patients with cholesteryl ester storage disease.

Lysosomal acid lipase (LAL) gene mutations were identified in three patients with cholesteryl ester storage disease (CESD). Direct sequencing of genomic DNA revealed that: patient 1 was a compound heterozygote for a P181L mutation and an A to G3' splice site substitution that causes skipping of exon 7, with a loss of 49 amino acids from LAL (delta 205-253); patient 2 was a compound heterozygote for a G66V mutation and a 5' splice site mutation (G to A) that leads to skipping of exon 8 (delta 254-277); and patient 3 was a compound heterozygote for a L273S mutation and an unidentified null allele. Furthermore, patients 2 and 3 showed a novel G-2A polymorphism that could be detected by an Xbal restriction fragment length polymorphism. All these mutants and a previously reported H274Y allele were expressed in vitro in HeLa cells using the vaccinia T7 expression system. The resulting recombinant proteins were inactive towards cholesteryl oleate and trioleylglycerol, demonstrating the direct involvement of these mutations in the pathogenesis of CESD. Immunoblotting of normal LAL expressed in HeLa cells revealed four major molecular forms, at least two of high molecular mass (54 and 50-51 kDa) and two of low molecular mass (42 and 43 kDa). L273S and P181L substitutions and delta 254-277 were shown to result in altered LAL molecular forms, some of which suggest that post-translational processing may interfere with the catalytic activity of LAL.

Child↗

Enrollment in the Health Alliance Plan HMO is not an independent risk factor for coronary artery bypass graft surgery.

BACKGROUND: Henry Ford Hospital is the sole provider of cardiac surgical services for the Health Alliance Plan, a health maintenance organization (HMO) that presently serves 450,000 enrollees. METHODS AND RESULTS: To determine the effect of managed care referral patterns on the outcome of coronary artery bypass graft (CABG) surgery, we retrospectively reviewed two concurrent groups of patients, 569 HMO patients and 225 patients with free-for-service (FFS) insurance, who had undergone isolated primary CABG surgery between January 1, 1990 and January 31, 1994. The 605 patients with Medicare operated on during the same time frame were excluded to obviate age bias. Age, sex, use of cardiac medications, history of prior percutaneous transluminal coronary angioplasty or thrombolytic therapy, history of recent and remote myocardial infarction, extent of coronary disease, presence of preexisting comorbid conditions, and incidence of unstable clinical syndromes and left ventricular dysfunction (ejection fraction < 40%) were comparable for both groups. In hospital mortality (HMO group, 1.9%; FFS group, 2.2%), mean ICU stay (HMO, 2.6 +/- 0.3 days; FFS, 2.3 +/- 0.3 days), and total hospital length of stay (HMO, 9.8 +/- 0.8 days; FFS, 8.6 +/- 0.6 days) were likewise similar. CONCLUSIONS: These data refute the notion that the gate-keeper mentality often associated with managed-care health insurance vehicles results in delayed referral of patients with coronary artery disease and results in suboptimal outcome.

Coronary Artery Bypass↗

Transesophageal echocardiographic evaluation of left main coronary artery.

Transesophageal echocardiography (TEE) demonstrated the left main coronary trunk in 30 of 32 patients. Of these 30 patients, 10 had angiographically normal and 20 stenotic left main coronary arteries. The TEE study revealed no stenosis in 9 of 10 patients with normal left main trunks and atherosclerotic lesions in all 20 patients with stenotic left main trunks. TEE demonstrated additional areas of stenosis in the left main coronary artery in 3 patients, which included ostial lesions in 2 patients. These features were not observed by angiography. Furthermore, when compared with angiography, TEE overestimated severity of stenosis in 4 patients. In conclusion, TEE is a useful test in demonstrating normal as well as stenotic left main coronary trunks.

Coronary Angiography↗

Discriminant analysis on small cell lung cancer and non-small cell lung cancer by means of NSE and CYFRA-21.1.

A correct diagnosis of small cell lung cancer (SCLC) and non-small cell lung cancer (NSCLC) is essential both for prognostic and therapeutic reasons. We used discriminant analysis as a method to optimize the discriminant power of serum tumour marker levels for differentiation between SCLC and NSCLC. A panel of serum markers, including neurone specific enolase (NSE), cytokeratin fragment antigen 21.1 (CYFRA-21.1), tissue polypeptide antigen (TPA) and carcinoembryonic antigen (CEA) was obtained in 50 consecutive NSCLC and 17 SCLC. Data were analysed by the BMDP statistical program after logarithmic transformation of marker levels. The variables selected were NSE and CYFRA-21.1. Considered together, they were able to give a 97% rate of correct classification. The formula generated (canonic variable, CV) was validated on a group of seven SCLC and 22 NSCLC patients. Only two errors occurred. We therefore conclude that the canonic variable tested, based on NSE and CYFRA-21.1, provides a good discrimination between the two types of lung cancer. The method is rapid, relatively inexpensive, and based on simple serum tests.

Aged↗

Evaluation of a novel tuberculosis complex-specific 34 kDa protein in the serological diagnosis of tuberculosis.

Tuberculosis (TB) serological testing with antigen complexes, although very sensitive, is not always as specific due to reactive serum antibodies in patients with inactive TB or nontuberculous infections. Since the use of recombinant M. tuberculosis proteins may enhance specificity, this study was designed to evaluate a novel 34 kDa tuberculosis complex-specific protein as a component of an antigen panel of recombinant proteins. Seventy patients with active TB (41 positive and 29 negative for acid-fast bacilli (AFB) in sputum) were evaluated, in comparison with 30 tuberculin purified protein derivative skin test positive (PPD+) and 30 PPD- normals, 20 subjects with inactive TB and 20 PPD+ subjects with nontuberculous pneumonia as controls. Serum antibody levels were quantified using enzyme linked immunosorbent assay (ELISA) tests with MS2-34, a fusion protein comprising the NH2-terminal 16 kDa of the 34 kDa protein, a recombinant 38 kDa protein (p38), and PPD. Using MS2-34 and p38 as an antigen panel in active TB patients yielded higher sensitivity and negative predictive value (sensitivity 86%; negative predictive value 91%) than using PPD (sensitivity 66%; negative predictive value 81%). Importantly, the MS2-34+p38 panel yielded a higher sensitivity (83%) than PPD (66%) in the subset of AFB- active TB patients. Thus, this novel protein increases sensitivity and specificity of serological testing for TB when used in panels of recombinant proteins.

Adolescent↗

Renal effects of dietary supplementation with fish oil in cyclosporine-treated liver transplant recipients.

Nephrotoxicity is the main untoward effect of cyclosporine (CsA) treatment. Experimental and clinical data suggest that dietary supplementation with fish oil may lessen cyclosporine nephrotoxicity, possibly by lowering renal thromboxane (Tx) production. We have studied the renal effects of a daily supplementation for 2 months of 12 g fish oil (18% C20:5 n-3 eicosapentaenoic acid [EPA] and 12% C22:6 n-3 docosahexanoic acid [DHA]) in a placebo-controlled (12 g corn oil), prospective, randomized, double-blind study of stable CsA-treated liver transplant recipients. Thirteen patients ingested corn oil capsules and 13 fish oil. Compliance with dietary regimen was confirmed by fatty acid chromatography that showed increased plasma concentrations of EPA (from 0.4 +/- 0.02% to 4.6 +/- 0.5%, P < .0001) and DHA (from 1.8 +/- 0.2% to 3.9 +/- 0.1%, P < .0001) in the fish oil group and increased plasma concentration of linoleic acid (C18:2 n-6) in the corn oil group (from 25 +/- 2% to 28.4 +/- 2%, P < .001). At the end of the 2 months of the study, in the fish oil group the effective renal plasma flow increased by 22% (P = .012), the glomerular filtration rate increased by 33% (P = .057), the renal blood flow increased by 17% (P = .024), and the calculated total renal vascular resistances decreased by 20% (P = .034). In contrast, none of these parameters changed in the corn oil group. The renal functional reserve determined during L-arginine infusion, plasma renin activity (PRA), and plasma aldosterone (PA) remained unchanged during the study in either group.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Evaluation of the response to chemotherapy in patients affected with small cell lung cancer using discriminant analysis: a preliminary report.

This report represents an attempt to combine the serum levels of more tumor markers together to evaluate the response to chemotherapy in 26 patients affected with small cell lung cancer (SCLC), by means of discriminant analysis. A pilot prospective study was performed on 26 subjects affected with inoperable SCLC (18 extensive diseases, and 8 limited diseases) and treated with chemotherapy (etoposide plus cisplatin regimen). Serum levels of a panel of tumor markers: Carcinoembryonic antigen (CEA), Tissue Polypeptide Antigen (TPA), Neuron Specific Enolase (NSE) and CYFRA -21.1 were determined before starting chemotherapy and at the restaging time (after 3 months). To optimize the classification power of these markers, a discriminant analysis was done, which permitted generating two classification functions, based on Tissue Polypeptide Antigen and Neuron Specific Enolase levels able to correctly classify 25 out of 26 subjects (8 progressions and 18 non progressions). The results obtained, furtherly confirm that tumor markers are useful to evaluate the chemotherapy response and indicate a possible approach to obtain the maximum usefulness of the serum marker levels.

Adult↗

Early blastic transformation of a myeloproliferative disorder with t(8;21) and progressive aberrations of chromosome 8.

We describe a case of a patient affected by a chronic myeloproliferative disorder with t(8;21)(q22;q22) and trisomy 8 at diagnosis. At the time of blastic metamorphosis, 2 months later, trisomy 8 metaphases were significantly reduced, while a predominance of t(8;21) was present. Finally, in the phase of leukemic regrowth following chemotherapy administration, monosomy 8 associated with der(21)t(8;21) was the predominant cytogenetic abnormality.

Chromosome Aberrations↗