Anti-leukocyte antibodies: LeukArrest (Hu23F2G) and Enlimomab (R6.5) in acute stroke

An abundance of experimental data show that inflammation contributes to cerebral ischaemic injury and that attenuation of the inflammatory response can improve outcome. The two clinical trials of therapy aimed at limiting the inflammatory response in acute stroke that have been carried out to date, however, have not shown a benefit to such therapy. The potential reasons for the failure of these trials are discussed.     

Failure mechanics of mitral valve chordae tendineae

BACKGROUND AND AIM OF THE STUDY: Rupture of chordae tendineae is the main cause of mitral valve insufficiency, and often requires corrective surgery. The precise mechanisms of chordal rupture, however, are unknown. METHODS: Failure mechanics were measured in porcine mitral valve chordae (37 anterior marginal, 40 anterior basal, 35 posterior marginal, and 38 posterior basal). Full-length chordae were weighed, measured, and stretched to failure in an Instron tensile testing machine. The ruptured ends were characterized under a dissecting microscope. RESULTS: Marginal chordae had 68% thinner cross-sectional areas and failed at 68% less load and 28% less strain than basal chordae. Chordae from the posterior leaflet were 35% thinner and failed at 43% less load and 22% less strain than anterior leaflet chordae. Failure strength was lowest for posterior marginal chordae. Chordae most frequently tore just below the leaflet insertion, in what was often their narrowest section. CONCLUSION: Overall, the marginal chordae and posterior leaflet chordae were thinner and required less strain and load to fail than basal chordae and anterior leaflet chordae, respectively. These results support previous reports of decreased extensibility in marginal chordae. The high incidence of ruptures in the posterior marginal chordae of diseased mitral valves may be due to an inherent weakness in these chordae.     

Moyamoya disease in Washington State and California

The authors identified 298 diagnoses of moyamoya in California and Washington from hospital discharge databases during the period 1987 to 1998. The incidence was 0.086/100,000 persons. The ethnicity-specific incidence rate ratios compared to whites were 4.6 (95% CI: 3.4 to 6.3) for Asian Americans, 2.2 (95% CI: 1.3 to 2.4) for African Americans, and 0.5 (95% CI: 0.3 to 0.8) for Hispanics. The incidence of moyamoya in Washington and California was lower than reported in Japan, but the rate among US Asians is similar.     

Dynamics of telomere erosion and its association with genome instability in myelodysplastic syndromes (MDS) and acute myelogenous leukemia arising from MDS: a marker of disease prognosis?

Telomere length was evaluated by terminal repeat fragment method (TRF) in 50 patients with myelodysplastic syndromes (MDS) and acute myelogenous leukemia (AML) arising from MDS and in 21 patients with untreated primary AML to ascertain, whether telomere erosion was associated with progression of MDS towards overt leukemia. Heterogeneity of TRF among MDS FAB subgroups (P=0.004) originated from its shortening in increased number of patients during progression of the disease. Chromosomal aberrations were present in 32% MDS patients with more eroded telomeres (P=0.022), nevertheless a difference between mean TRF in the subgroups with normal and abnormal karyotype diminished during progression of MDS. A negative correlation between individual TRF and IPSS value (P=0.039) showed that telomere dynamics might serve as a useful prognostic factor for assessment of an individual MDS patient's risk and for decision of an optimal treatment strategy.     

Enhancement of the humoral immune response by Echinacea purpurea in female Swiss mice

Various preparations of the plant Echinacea purpurea have been investigated for their potential to enhance immune function, primarily through activation of innate immune responses. Few studies have examined the potential for enhancement of humoral immunity. Using female Swiss mice we administered a volumetric dose of a glycerine extract of E. purpurea by oral gavage, to evaluate effects on the IgM specific antibody forming cell (AFC) response. Four days of treatment following immunization with sheep red blood cells (SRBC) produced a significant enhancement over naive controls at doses of 0.4 and 0.8 mL/kg/day. A few clinical trials and anecdotal reports have suggested that the greatest efficacy for E. purpurea occurs in acute use following onset of illness. A time course study, using the time of SRBC immunization to mimic the onset of illness, examined the effects of 8 and 4 days of E. purpurea treatment at 0.6 mL/kg/day. Only in the 4-day administration, with dosing beginning 1 hour after SRBC immunization, was there an observed enhancement of the antibody forming cell response. This supports the acute use of E. purpurea as suggested by anecdotal reports, and demonstrates the potential for enhancement of humoral immune responses as well as innate immune responses.     

A prognostic impact of separation of refractory cytopenia with multilineage dysplasia and 5q- syndrome from refractory anemia in primary myelodysplastic syndrome

A prognostic impact of WHO classification of myelodysplastic syndrome (MDS) was studied in a group of 103 primary MDS patients with refractory anemia (RA) according to French-American-British (FAB) classification. Median survival of 37 patients with RA according to WHO criteria of 85.2 months was significantly different from that in both 37 patients with refractory cytopenia with multilineage dysplasia (RCMD) (47.0 months, P=0.002) and 29 patients with 5q- abnormality diagnosed by routine chromosome banding (36.2 months, P=0.0002). A more detailed karyotype analysis with fluorescent in situ hybridization (FISH) techniques confirmed 5q deletion as a sole cytogenetic abnormality in only 12 out of 29 patients, in 4 patients 5q- was associated with complex abnormalities involving 5q region, 13 patients had 5q deletion combined with further karyotype abberations outside 5q. No difference in median survival and estimated 3 years survival was observed between RA patients, patients with 5q- syndrome according to WHO morphology criteria and patients with 5q- as a single abnormality confirmed by FISH in contrast to patients with either additional 5q abberations or further karyotype changes not involving 5q. The same difference was also observed in time to 25% of patients evolving to acute myeloid leukemia (AML). Our study confirmed usefulness of separation of RCMD from RA. RCMD represents a poor prognostic subgroup of MDS clearly distinct from pure RA mainly due to short survival connected with progressive bone marrow failure and increased risk of leukemic transformation. We also suggest to define 5q- syndrome as primary MDS of FAB type RA with 5q deletion as a sole cytogenetic abnormality confirmed by FISH analysis. This definition enabled us to discriminate 5q- patients with favorable prognosis similar as in RA from those with poor outcome associated with 5q- combined with complex abnormalities involving either 5q or regions outside 5q.     

The psychiatrist in the community vs the district psychiatrist. Two sides of the coin. The problem of involuntary commitment

Psychiatrists often come into contact with mentally ill patients whom they believe would benefit from medical treatment. However, the legal requirements of a commitment order present a frustrating, and sometimes unnecessary, obstacle to such treatment.     

The 6-min walk distance, peak oxygen uptake, and mortality in COPD

In patients with COPD, the maximal oxygen uptake (Vo2) measured at peak exercise and the 6-min walk distance (6MWD) have been associated with survival; however, no study has compared the strength of the association in the same patients. In this study, we compared the association between the 6MWD and peak Vo2 and mortality in 365 patients with COPD. Patients' cardiopulmonary cycle ergometry test results and 6MWD were determined at entry, and patients were followed up for a mean period of 67 months. There were 171 deaths. Compared with survivors, nonsurvivors were older (mean [+/- SD] age, 67.9 +/- 8 vs 65.9 +/- 8 years, respectively; p = 0.008), had worse mean FEV1 (36.5 +/- 12 vs 42.6 +/- 14 L, respectively; p = 0.02), had lower mean peak Vo2 (9.8 +/- 3 vs 11.8 +/- 3.6 mL/Kg/min, respectively; p < 0.0001), lower mean 6MWD (312 +/- 104 vs 377 +/- 95 m, respectively; p < 0.0001), and lower mean exercise minute ventilation (37.4 +/- 12 vs 42.3 +/- 13 L/min, respectively; p = 0.004). Univariate analysis showed that peak Vo2 and 6MWD as well as comorbidity, FEV1, and body mass index were associated with death. Logistic regression analysis with mortality as the dependent variable revealed that 6MWD (hazard ratio [HR], 0.996; 95% confidence interval [CI], 0.993 to 0.999; p < 0.01) had a stronger association than the peak Vo2 (HR, 0.971; 95% CI, 0.959 to 1.000; p = 0.050) with mortality. This study shows the 6MWD is as good predictor of mortality as the peak Vo2 in patients with COPD.