Predischarge two-dimensional echocardiographic evaluation of left ventricular thrombosis after acute myocardial infarction in the GISSI-3 study

Left ventricular (LV) thrombosis can be found in patients with acute myocardial infarction (AMI). No wide multicenter trial on AMI has provided information about LV thrombosis until now. The protocol of the GISSI-3 study included the search for the presence of LV thrombosis in patients from 200 coronary care units that did not specifically focus on LV thrombosis. We examined the GISSI-3 database results related to 8,326 patients at low to medium risk for LV thrombi in which a predischarge echocardiogram (9 +/- 5 days) was available. LV thrombosis was found in 427 patients (5.1%): 292 of 2,544 patients (11.5%) with anterior AMI and in 135 of 5,782 patients (2.3%) with AMI in other sites (p <0.0001). The incidence of LV thrombosis was higher in patients with ejection fraction < or = 40% (151 of 1,432 [10.5%] vs 276 of 6,894 [4%]; p <0.0001) both in the total population and in the subgroup with anterior AMI (106 of 597 [17.8%] vs 186 of 1,947 [9.6%]; p <0.0001). Multivariate analysis showed that only the Killip class > I and early intravenous beta-blocker administration were independently associated with higher LV thrombosis risk in the subgroup of patients with anterior AMI (odds ratio 1.75, 95% confidence interval 1.28 to 2.39; odds ratio 1.32, 95% confidence interval 1.02 to 1.72, respectively). In patients with anterior AMI, oral beta-blocker therapy given or not given after early intravenous beta-blocker administration does not influence the occurrence of LV thrombosis. The rate of LV thrombosis was similar in patients treated or not treated with nitrates and lisinopril both in the total population and in patients with anterior and nonanterior AMI. In conclusion, in the GISSI-3 population at low to medium risk for LV thrombi, the highest rate of occurrence of LV thrombosis was found among patients with anterior AMI and an ejection fraction < 40%. Killip class > I and the early intravenous beta-blocker administration were the only variables independently associated with a higher predischarge incidence of LV thrombosis after anterior AMI.     

Vertical ridge augmentation around dental implants using a membrane technique and autogenous bone or allografts in humans

This study investigated the effect on vertical bone regeneration of the addition of demineralized freeze-dried bone allograft or autogenous bone chips to a membrane technique. Twenty partially edentulous patients with vertical jawbone deficiencies were selected for this study. The patients were divided into two groups of 10 individuals. The 10 patients of Group A received 26 Br?nemark implants in 10 surgical sites. The 10 patients of Group B received 32 implants in 12 surgical sites. Fifty-two out of 58 implants (22 in Group A and 30 in Group B) extended 1.5 to 7.5 mm superior to the bone crest. Titanium-reinforced expanded polytetrafluoroethylene membranes were used to cover the implants and, before complete membrane fixation, demineralized freeze-dried bone allograft particles were condensed under the membrane in Group A, and autogenous bone chips were used in Group B. At the reentry after 7 to 11 months the membranes were removed and a small biopsy was collected from 11 sites comprehending the miniscrews. The clinical measurements from Group A demonstrated a mean vertical bone gain of 3.1 mm (SD = 0.9 mm, range 1 to 5 mm) with a mean percentage of bone gain of 124% (SD = 46.6%). The measurements from Group B showed a mean vertical bone gain of 5.02 mm (SD = 2.3 mm, range 1 to 8.5 mm) with a mean percentage of bone gain of 95% (SD = 26.8%). Histomorphometric analysis of the present study clearly demonstrated a direct correlation between the density of the pre-existing bone and the density of the regenerated bone. The mean percentage of new bone-titanium contact was from 39.1% to 63.2%, depending on the quality of the pre-existing bone. Both the clinical and histologic results indicate a beneficial effect of the addition of demineralized freeze-dried bone allograft or autogenous bone particles to vertical ridge augmentation procedures in humans.     

Determination of nimesulide and hydroxynimesulide in human plasma by high performance liquid chromatography

Two specific methods for the simultaneous determination of nimesulide, a non steroidal anti-inflammatory drug, and its hydroxylated metabolite in human plasma are described. Adopting a high performance liquid chromatographic (HPLC) system with UV detection (230 nm), the compounds, extracted from plasma in acidic medium, were separated on ODS columns under gradient conditions, using a phosphate buffer solution and methanol as mobile phase. For each method column length, gradient rate and composition were appropriately selected. The limit of quantitation was 25 ng/mL for both compounds. The two methods were validated by intra day assays at three concentration levels and applied in kinetic studies in healthy volunteers, during which inter-day assays were carried out confirming their feasibility.     

Molecular basis of resistance to HIV-1 protease inhibition: a plausible hypothesis

The binding thermodynamics of the HIV-1 protease inhibitor acetyl pepstatin and the substrate Val-Ser-Gln-Asn-Tyr-Pro-Ile-Val-Gln, corresponding to one of the cleavage sites in the gag, gag-pol polyproteins, have been measured by direct microcalorimetric analysis. The results indicate that the binding of the peptide substrate or peptide inhibitor is entropically driven; i.e., it is characterized by an unfavorable enthalpy and a favorable entropy change, in agreement with a structure-based thermodynamic analysis based upon an empirical parameterization of the energetics. Dissection of the binding enthalpy indicates that the intrinsic interactions are favorable and that the unfavorable enthalpy originates from the energy cost of rearranging the flap region in the protease molecule. In addition, the binding is coupled to a negative heat capacity change. The dominant binding force is the increase in solvent entropy that accompanies the burial of a significant hydrophobic surface. Comparison of the binding energetics obtained for the substrate with that obtained for synthetic nonpeptide inhibitors indicates that the major difference is in the magnitude of the conformational entropy change. In solution, the peptide substrate has a higher flexibility than the synthetic inhibitors and therefore suffers a higher conformational entropy loss upon binding. This higher entropy loss accounts for the lower binding affinity of the substrate. On the other hand, due to its higher flexibility, the peptide substrate is more amenable to adapt to backbone rearrangements or subtle conformational changes induced by mutations in the protease. The synthetic inhibitors are less flexible, and their capacity to adapt is more restricted. The expected result is a more pronounced effect of mutations on the binding affinity of the synthetic inhibitors. On the basis of the thermodynamic differences in the mode of binding of substrate and synthetic inhibitors, it appears that a key factor to understanding resistance is given by the relative balance of the different forces that contribute to the binding free energy and, in particular, the balance between conformational and solvation entropy.     

Demographic study of first-ever stroke and acute myocardial infarction in Okinawa, Japan

We performed a cross-sectional survey of stroke and acute myocardial infarction (AMI) in Okinawa, Japan with a census population of about 1.2 million. A total of 3,644 cases of first-ever stroke and 898 cases of initial acute myocardial infarction (AMI) were detected. The age-adjusted annual incidence rate for stroke was 105 per 100,000 standard population of Japan, and that of AMI was 26. The case-fatality rate of stroke within 28 days of onset was 12.8%, and that of AMI was 22.2%. Of the stroke cases, 51.4% were diagnosed as brain infarction, 38.7% as brain hemorrhage, and 9.3% as subarachnoid hemorrhage. The diagnosis of stroke subtypes were confirmed by computed tomography or magnetic resonance imaging in 98.4% of all stroke cases. In Okinawa, the incidence rate of AMI was still considerably lower than that in the Western population, and the rate of stroke was similar to that in the Western population.     

Ulcerative colitis with skip lesions at the mouth of the appendix: a clinical study

OBJECTIVE: We examined the clinical characteristics of ulcerative colitis patients who demonstrated endoscopically discontinuous lesions at the mouth of the appendix. METHODS: Of patients with initial or recurrent active ulcerative colitis who underwent total colonoscopy during the past 3 yr at Osaka City General Hospital, we selected those who had skip lesions in the mouth of the appendix before treatment, and examined their gender, age, disease type, sites of lesions, inflammatory reaction, severity of disease, effects of treatment, and posttreatment course. RESULTS: Discontinuous lesions at the mouth of the appendix were found in 10 patients, who had the following common clinical features: the major lesion was usually present in the lower part of the large bowel including the rectum, many of the patients had suffered an initial attack only, all patients had mild disease, and many of the patients responded quite satisfactorily to treatment with salicylazosulfapyridine. CONCLUSION: Numerous patients with ulcerative colitis with discontinuous lesions at the mouth of the appendix were observed and their clinical characteristics were examined. Determination of the clinical significance of skip lesions in the appendix will contribute to elucidation of the pathogenesis of ulcerative colitis.