Relation between regional and global systolic function in patients with ischemic cardiomyopathy after β-Blocker therapy or revascularization

Background

To assess the relationship between improved regional and global myocardial function in patients with ischemic cardiomyopathy in response to β-blocker therapy or revascularization.

Materials and methods

Cardiovascular Magnetic Resonance (CMR) was performed in 32 patients with ischemic cardiomyopathy before and 8 ± 2 months after therapy. Patients were assigned clinically to β-blocker therapy (n = 20) or revascularization (n = 12). CMR at baseline was performed to assess regional and global LV function at rest and under low-dose dobutamine. Wall thickening was analyzed in dysfunctional, adjacent, and remote segments. Follow-up CMR included rest function evaluation.

Results

Augmentation of wall thickening during dobutamine at baseline was similar in dysfunctional, adjacent and remote segments in both patient groups. Therefore, baseline characteristics were similar for both patient groups. In both patient groups resting LV ejection fraction and end-systolic volume improved significantly (p < 0.05) at follow-up. Stepwise multivariate analysis revealed that improvement in global LV ejection fraction in the β-blocker treated patients was significantly related to improved function of remote myocardium (p < 0.05), whereas in the revascularized patients improved function in dysfunctional and adjacent segments was more pronounced (p < 0.05).

Conclusion

In patients with chronic ischemic LV dysfunction, β-Blocker therapy or revascularization resulted in a similar improvement of global systolic LV function. However, after β-blocker therapy, improved global systolic function was mainly related to improved contraction of remote myocardium, whereas after revascularization the dysfunctional and adjacent regions contributed predominantly to the improved global systolic function.     

Sodium butyrate enhances fetal globin gene expression in erythroid progenitors of patients with Hb SS and beta thalassemia

Increasing the expression of the gamma globin genes is considered a useful therapeutic approach to the beta globin diseases. Because butyrate and alpha-amino-n-butyric acid (ABA) augment gamma globin expression in normal neonatal and adult erythroid progenitors, we investigated the effects of sodium butyrate and ABA on erythroid progenitors of patients with beta thalassemia and sickle cell anemia who might benefit from such an effect. Both substances increased fetal hemoglobin (Hb F) expression in Bfu-e from 7% to 30% above levels found in control cultures from the same subjects with sickle cell anemia. The fraction of cultured erythroblasts producing Hb F increased more than 20% with sodium butyrate treatment in 70% of cultures. In most cultures, this produced greater than 20% total Hb F and greater than 70% F cells, levels which have been considered beneficial in ameliorating clinical symptoms. Alpha: non-alpha (alpha-non-alpha) imbalance was decreased by 36% in erythroid progenitors of patients with beta thalassemia cultured in the presence of butyrate compared with control cultures from the same subjects. These data suggest that sodium butyrate may have therapeutic potential for increasing gamma globin expression in the beta globin diseases.     

Neurophysiologic assessment of the anal sphincters

One hundred twenty consecutive patients with either fecal incontinence (60 patients), chronic constipation (41 patients), or idiopathic intractable pelvic pain (19 patients) were prospectively assessed. Patients underwent concentric needle electromyography (EMG), bilateral pudendal nerve terminal motor latency evaluation, anorectal manometry, and cinedefecography. The most common EMG finding in patients with fecal incontinence was decreased recruitment of motor units with squeezing and polyphasic motor unit potentials; these are consistent with an injury pattern. The most common EMG finding in the constipated patients was paradoxical puborectalis contraction. This latter abnormality was also a frequent finding in patients with rectal pain, as was prolongation of pudendal nerve latency. Paradoxical puborectalis contraction was diagnosed more frequently with EMG than with cinedefecography. Inter-examination correlation was best in the incontinent group between EMG and manometry. Cinedefecography had poor correlation with EMG in all patient groups but was valuable in the detection of additional pathology such as rectoanal intussusception and anterior rectocele. Electromyography including pudendal nerve terminal motor latency assessment is a valuable adjunct in the evaluation of disorders of evacuation. The information it yields is complementary to that offered by more routine physiologic examinations.     

Analysis of interphase cells for the Philadelphia translocation using painting probe made by inter-Alu-polymerase chain reaction from a radiation hybrid

Fluorescence in situ hybridization (FISH) probe for the identification of the Philadelphia (Ph) translocation [t(9;22) (q34;q11)] in chronic myelogenous leukemia cells was developed by inter-Alu-polymerase chain reaction of DNA from an interspecific somatic cell hybrid containing approximately 5 Mb of human DNA covering the ABL gene region on human chromosome 9q34. This probe was large enough to be effective in identifying the genomic domains yet small enough to resolve them in more than 90% of bone marrow interphase cells. Combination of the probe with a cosmid contig probe for the BCR region of chromosome 22 in two- color FISH reduced the frequency of false-positive identification of the Ph chromosome to less than 1%. The procedure allows detection of as few as 1% Ph+ cells independent of the cycling status or BCR/ABL expression level of cells, and the quantitation of non-Ph chromosome- containing interphase nuclei in the marrow of patients judged 100% Ph+ by standard cytogenetics.     

Cerebral vasculitis--recognition, diagnosis and management

Cerebral vasculitis is a serious but uncommon condition which presents considerable difficulties in recognition, diagnosis and treatment. We studied eight consecutive patients in whom this diagnosis was made. Despite the great diversity of symptoms and signs, we noted three clinical patterns: (i) acute or sub-acute encephalopathy, (ii) a picture with some similarities to multiple sclerosis ('MS-plus'), and (iii) features of a rapidly progressive space-occupying lesion. The identification of these patterns may help recognition of cerebral vasculitis. The diagnostic value of four investigative procedures not previously studied in cerebral vasculitis was assessed: ophthalmological examination using low-dose fluorescein angiography with slit-lamp video microscopy of the anterior segment (abnormal in 4/5 patients); spinal fluid oligoclonal band analysis (abnormal in 3/6 patients); anti-neutrophil cytoplasmic antibody assay (abnormal in 3/8 patients); and indium-labelled white-cell cerebral imaging (positive in only one patient). Treatment was with steroid alone (n = 2) or steroid with cyclophosphamide (n = 6). Seven patients responded clinically.      

The binding of bovine factor XII to kaolin

Purified bovine factor XII was radiolabeled with iodine-125 and its binding to kaolin studied. Binding was rapid and was not readily reversible upon adding unlabeled factor XII. The optimum pH for binding was in the region of pH 5-7. The isoelectric point of factor XII was pH 5.7. High concentrations of urea or increasing the ionic strength of the medium did not inhibit binding. Polyvalent macromolecules, such as Polybrene and polylysine, were effective inhibitors of factor XII binding to kaolin. Polylysine caused the release of factor XII that had bound to the kaolin surface.     

Selective increase of potassium permeability in red blood cells exposed to acetylphenylhydrazine

Normal human red blood cells, when exposed briefly to acetylphenylhydrazine (APH), acquire Heinz bodies and a propensity for net ion and water loss upon subsequent incubation in an APH-free medium of physiologic sodium and potassium (K) content. The cells can be protected from APH damage by previous deoxygenation. The ion and water loss depend on the presence of a K gradient from cell to medium. In contradistinction to some other types of membrane perturbation in which K permeability is increased, the APH effect is not dependent on calcium. The meaning of these observations is discussed in relation to the vulnerability of the K permeability barrier.     

High-dose chemotherapy with or without total body irradiation followed by autologous bone marrow and/or peripheral blood stem cell transplantation for patients with relapsed and refractory Hodgkin's disease: results in 85 patients with analysis of prognostic factors

Eight-five consecutive patients with relapsed or refractory Hodgkin's disease (HD) underwent high-dose chemotherapy or chemo/radiotherapy followed by autologous bone marrow (ABMT) and/or peripheral blood stem cell (PBSC) transplantation. Two preparative regimens were used. Twenty- two patients (26%) without prior radiation received fractionated total body irradiation (FTBI) 1,200 Gy in combination with high-dose etoposide (VP-16) 60 mg/kg and cyclophosphamide (CTX) 100 mg/kg. Sixty- three patients (74%) with prior radiotherapy received carmustine (BCNU) 450 mg/m2 instead of FTBI. The median age was 32 years (range, 16 to 56). The median number of prior chemotherapy regimens was three (range, 1 to 7). Forty-three patients (51%) received transplants in first relapse or second complete remission (CR), whereas 33 (39%) received transplants after second or subsequent relapse. All relapsed patients, except one, received conventional salvage chemotherapy and/or radiotherapy in an attempt to reduce tumor bulk before transplant. At the time of analysis in April 1994, fifty-seven patients (67%) are alive, including 44 (52%) in continuous CR, with a median follow-up for the surviving patients of 28 months (range, 7 to 66). Thirty patients (35%) relapsed at a median of 9 months (range, 1 to 43). Eleven patients (13%) died of transplant-related complications including veno- occlusive disease of the liver (VOD) in five, acute and late interstitial pneumonitis in three, graft failure in one, cerebral hemorrhage in one, and therapy-induced myelodysplasia (MDS)/acute leukemia in one patient. At a median follow-up of 25 months (range, 0.6 to 66), the cumulative probability of 2-year overall and disease-free survival (DFS) of all 85 patients is 75% (95% confidence interval [CI] 64% to 84%) and 58% (95% CI 47% to 69%), respectively. Three independent prognostic variables were identified by univariate analysis: number of prior chemotherapy regimens, prior radiotherapy, and extranodal disease at ABMT. Multivariate stepwise Cox regression identified the number of prior chemotherapy regimens as the only significant prognostic factor predicting for both relapse and DFS. There were no significant differences in the outcome of the treatment between the two preparative regimens. Our results confirm that high- dose therapy and ABMT is an effective therapy for patients with relapsed or refractory HD. Earlier transplantation is recommended before the development of drug resistance and end organ damage that results from repeated attempts of salvage therapy.