Comparing different methods for homocysteine determination.

Slightly elevated values of homocysteine are commonly associated with thromboembolic diseases, while high values can be found in patients with congenital metabolic defects or nutritional problems. The clinical use of homocysteine as an independent marker of cardiovascular disease was limited in the past by technical problems with its measurement, the instrumentation (HPLC, radioenzymatic assays, gas chromatography-mass spectrometry, etc.) and the necessary skills required. Commercially available immunoassays now permit a simpler and more rapid measurement of homocysteine, that is more suitable for routine clinical laboratories; in this paper we analyze the results obtained by using three fully automated methods for homocysteine determination (Abbott IMx immunoassay, Abbott AxSYM immunoassay and Immulite 2000 homocysteine immunoassay) and their correlation with the widely used HPLC method. The results clearly indicate that all three automated immunochemical methods correlate well with the HPLC method (slope 0.97-1.03; intercept 0.95-1.91 with a recovery above 95% for all three methods).     

Weekly subcutaneous recombinant human erythropoietin corrects anemia of progressive renal failure

PURPOSE: The purpose of this study was to analyze data retrospectively from our use of weekly subcutaneous recombinant human erythropoietin (rHuEPO) in predialysis and peritoneal dialysis patients with anemia. PATIENTS AND METHODS: All anemic patients with progressive renal failure (12 predialysis and seven home peritoneal dialysis) in whom subcutaneous rHuEPO therapy was begun at, or was reduced to, a weekly dose were studied retrospectively. Patients were not selected for, nor excluded from, these observations for any other reason. Hematocrit and endogenous creatinine clearance were monitored regularly, and no other new treatment for anemia was given except oral iron. Iron-deficiency anemia was considered improbable because of normal red blood cell mean corpuscular volume. Unfortunately, iron parameters were not monitored. RESULTS: The hematocrit increased 4 to 9 percentage points in 4 to 13 weeks in all but two patients who were initially treated with weekly doses, and a hematocrit of 31% was achieved in these patients within 6 to 12 weeks. The mean effective dose to accomplish this was 150 U/kg. All but three patients could be maintained on weekly doses at a hematocrit of 31% or higher. The mean effective dose was 75 U/kg. CONCLUSION: It is concluded that subcutaneous rHuEPO administered weekly can correct the anemia of predialysis and peritoneal dialysis patients. Weekly dosing is more convenient for patients and may be less costly for Medicare providers.     

Aerobic exercise performance correlates with post-ischemic flow-mediated dilation of the brachial artery in young healthy men

In older healthy men, aerobic exercise capacity is related to postischemic flow-mediated dilation of the brachial artery (FMD), but corresponding data in a younger population is not available. In addition, whether submaximal aerobic exercise performance also correlates with this kind of vasomotor reactivity is not known. Therefore, in 15 nonsmoking young healthy men [age 27 (5) years; body mass index: 24 (2) kg/m²; mean (SD)] with different levels of ordinary physical activity, but not performing upper-extremity training, we measured FMD at 1 min after reactive hyperemia, and pulmonary oxygen uptake (O₂) at ventilatory anaerobic threshold (O₂AT) and at peak effort (peak O₂) during an incremental exercise on a treadmill. In our participants, FMD was 9.1 (3.4)%, O₂AT was 40.72 (5.92) ml/kg per min, and peak O₂ was 52.95 (8.13) ml/kg per min. Using bivariate Pearsons correlation, and in separate multivariate regression analyses, O₂AT and peak VO₂ showed a significant and reasonably good correlation with FMD (r=0.84, P<0.001 and r=0.77, P=0.001, respectively), independent of age, body mass index and serum total cholesterol (=0.77, P<0.001, R² of the overall model=0.79 and =0.70, P<0.005, R² of the overall model=0.69, respectively). Our data provide evidence suggesting that in young healthy men a higher submaximal and maximal aerobic exercise performance is associated with a greater FMD of peripheral conduit arteries.     

Presence of Rickettsia conorii subsp. israelensis, the causative agent of Israeli spotted fever, in Sicily, Italy, ascertained in a retrospective study

A retrospective analysis by molecular-sequence-based techniques was performed to correctly identify the etiological agent of 24 Mediterranean spotted fever cases occurring in Western Sicily, Italy, from 1987 to 2001. Restriction analysis of a 632-bp PCR-amplified portion of the ompA gene allowed presumptive identification of five clinical isolates as belonging to Rickettsia conorii subsp. israelensis, the etiological agent of Israeli spotted fever (ISF). The remaining 19 rickettsial isolates were Rickettsia conorii subsp. conorii, the only pathogenic rickettsia of the spotted fever group reported in Italy until the present. Sequence analysis of the ompA gene confirmed the identification of all the R. conorii subsp. israelensis isolates and demonstrated that rickettsiosis caused by R. conorii subsp. israelensis can be traced back to 1991 in Sicily. The recorded clinical data of the five ISF patients support the idea that these strains could correlate to more-severe forms of human disease. Three of five patients experienced severe disease, and one of them died.     

Inhibition by anti-HLA class II monoclonal antibodies of monocyte-dependent T cell proliferation induced by monoclonal antibody OKT3

The inhibitory effect of monoclonal antibodies (mAb) to monomorphic (locus-restricted and locus-shared) and polymorphic determinants of HLA class II antigens on the monocyte-dependent proliferation of T cells stimulated with mAb OKT3 has been studied. The effect appears to be specific, dose dependent, is not mediated by the Fc portion of mAb and reflects their interaction with the corresponding determinants. The anti-HLA class II mAb do not have to be present in the culture throughout the incubation period, but are essential in early phases of mAb OKT3 T cell activation. Both monocytes and T cells are the targets of the inhibition exerted by the anti-HLA class II mAb. Their inhibitory effect involves several steps in the sequence of events which leads to T cell proliferation, including interleukin (IL) 1 and 2 secretion, and IL2 receptor expression.     

Fever of unknown origin in a Mediterranean survey from a division of internal medicine: report of 91 cases during a 12-year-period (1991–2002)

Despite the availability of all advanced diagnostic tools, fever of unknown origin (FUO) remains a diagnostic challenge for physicians. The objective was to define, through a retrospective study, the categories of the diseases of Sicilian patients admitted at the Department of Clinical Medicine and Emerging Diseases, University of Palermo, Italy, for classical FUO. Using the registration system for patients admitted from 1991 to 2002, 508 charts of patients admitted because of fever were reviewed. Of these, only 91 patients fulfilled the criteria for classical FUO. The origin of FUO was diagnosed in 62 (68.1%) patients. Infection was the most common cause of FUO with 29 cases (31.8% of total of FUO), neoplasms accounted for 13 cases (14.2%), collagen vascular disease for 11 cases (12.0%), and miscellaneous for 9 cases (9.8%). Undiagnosed FUO were 29 (31.8%) and, of them, 22 cases were followed-up for 2 years. A definite diagnosis could be established only in 8 cases, 13 subjects completely recovered and 4 of them died. In the 73.4% of cases, the FUO have been the result of misleading factors in the diagnostic approaches as made by the physician. The results of our study are similar to those already reported by other authors in other populations, with infections as first, neoplasm as second, and collagen vascular diseases as third most important causes of FUO. In our study the prognosis for undiagnosed FUO cases was good, but a definite diagnosis could be established only in few cases. Therefore, further multicentric, prospective studies of good design are required.     

In-stent fractional flow reserve variations and related optical coherence tomography findings: the FFR–OCT co-registration study

We sought to assess in-stent variations in fractional flow reserve (FFR) in patients with previous percutaneous coronary intervention (PCI) and to associate any drop in FFR with findings by optical coherence tomography (OCT) imaging. Suboptimal post-PCI FFR values were previously associated with poor outcomes. It is not known to which extent in-stent pressure loss contributes to reduced FFR. In this single-arm observational study, 26 patients who previously underwent PCI with drug-eluting stent or scaffold implantation were enrolled. Motorized FFR pullback during continuous intravenous adenosine infusion and OCT assessments was performed. Post-PCI FFR?<?0.94 was defined as suboptimal. At a median of 63 days after PCI (interquartile range: 59–64 days), 18 out of 26 patients (72%) had suboptimal FFR. The in-stent drop in FFR was significantly higher in patients with suboptimal FFR vs. patients with optimal FFR (0.08?±?0.07 vs. 0.01?±?0.02, p?<?0.001). Receiver operating characteristic curve analysis showed that an in-stent FFR variation of >?0.03 was associated with suboptimal FFR. In patients with suboptimal FFR, the OCT analyses revealed higher mean neointimal area (respectively: 1.06?±?0.80 vs. 0.51?±?0.23 mm²; p?=?0.018) and higher neointimal thickness of covered struts (respectively 0.11?±?0.07 vs. 0.06?±?0.01 mm; p?=?0.021). Suboptimal FFR values following stent-implantation are mainly caused by significant in-stent pressure loss during hyperemia. This finding is associated to a larger neointimal proliferation.