Intermediate-dose cytarabine plus mitoxantrone versus standard-dose cytarabine plus daunorubicin for acute myeloid leukemia in elderly patients.

Background: The combination of intermediate-dose cytarabine plus mitoxantrone (IMA) can induce high complete remission rates with acceptable toxicity in elderly patients with acute myeloid leukemia (AML). We present the final results of a randomized-controlled trial comparing IMA with the standard 7 + 3 induction regimen consisting of continuous infusion cytarabine plus daunorubicin (DA). Patients and methods: Patients with newly diagnosed AML >60 years were randomized to receive either intermediate-dose cytarabine (1000 mg/m2 twice daily on days 1, 3, 5, 7) plus mitoxantrone (10 mg/m2 days 1-3) (IMA) or standard induction therapy with cytarabine (100 mg/m2 continuously days 1-7) plus daunorubicin (45 mg/m2 days 3-5) (DA). Patients in complete remission after DA received intermediate-dose cytarabine plus amsacrine as consolidation treatment, whereas patients after IMA were consolidated with standard-dose cytarabine plus mitoxantrone. Results: Between February 2005 and October 2009, 485 patients were randomized; 241 for treatment arm DA and 244 for IMA; 76% of patients were >65 years. The complete response rate after DA was 39% [95% confidence interval (95% CI): 33-45] versus 55% (95% CI: 49-61) after IMA (odds ratio 1.89, P = 0.001). The 6-week early-death rate was 14% in both arms. Relapse-free survival curves were superimposable in the first year, but separated afterwards, resulting in 3-year relapse-free survival rates of 29% versus 14% in the DA versus IMA arms, respectively (P = 0.042). The median overall survival was 10 months in both arms (P = 0.513). Conclusion: The dose escalation of cytarabine in induction therapy lead to improved remission rates in the elderly AML patients. This did not translate into a survival advantage, most likely due to differences in consolidation treatment. Thus, effective consolidation strategies need to be further explored. In combination with an effective consolidation strategy, the use of intermediate-dose cytarabine in induction may improve curative treatment for elderly AML patients.

[Diagnostics and exclusion of hereditary angioedema : a standarized approach for the practice]. / Diagnostik und Ausschluss des hereditären Angioödems : Ein standardisierter Ansatz für die Praxis.

The differentiation between mast cell mediator-mediated and bradykinin-mediated forms of angioedema can be difficult. Bradykinin-mediated hereditary angioedema is a rare autosomal dominant hereditary disease which is characterized by recurrent edema attacks of varying magnitude. The edema occurs in the skin and mucous membranes and can be temporarily disfiguring, very painful and life-threatening by attacks in the laryngeal region. Because of the multitude of differential diagnoses, a final diagnosis is only achieved after an average duration of more than 10 years. The anamnestic and laboratory diagnostic algorithm presented here is designed to assist a simpler differentiation of the various forms of angioedema and to reach the correct diagnosis more quickly.

[Patients with chronic low back pain: the impact of psychosocial features]. / Patienten mit chronisch unspezifischem Rückenschmerz: Zur Bedeutung psychosozialer Merkmale.

BACKGROUND: Chronic low back pain (CLBP) is often associated with clinical and subclinical levels of psychological problems. A higher stage of chronicity is associated with an increase in co-existing psychological disorders. Previous programmes of inpatient orthopaedic rehabilitation reveal little evidence of sustained rehabilitation effects, a finding which may be attributable to the absence of specific psychological treatment during the programme. PURPOSE: Does cognitive-behavioural depression management training in patients with CLBP and depressive symptoms improve the inpatient orthopaedic rehabilitation success depending on the stage of chronicity? METHOD: Effects of the new programme on psychological well-being (ADS depressive symptoms, HADS anxiety, SCL somatization and mental health of the SF-12) were investigated in n=75 patients with first and second stage of chronicity immediately after, six months after and 24 months after rehabilitation and were compared to standard rehabilitation without management of depressive symptoms. RESULTS: All patients benefited from both treatments immediately after rehabilitation. However, six months after rehabilitation only patients of the intervention group showed significant beneficial effects with regard to depressive symptoms and mental health. The lowered depressive symptoms remained stable up to the 24-month follow-up assessment. Anxiety in the second stage of chronicity was reduced up to the 6-month follow-up and in the first stage up to the 24-month follow-up. CONCLUSIONS: The new programme with a cognitive-behavioural depression management training revealed beneficial effects on mental health in the mid-term and on depressive symptoms in the long-term. However, the effects need to be further improved by after-care programmes.

[Pain staging, gender, and rehabilitation outcome in chronic low back pain. A pilot study]. / Schmerzchronifizierung, Geschlecht und Rehabilitationserfolg bei chronischem Rückenschmerz. Eine Pilotstudie.

BACKGROUND: Current biopsychosocial models of the etiology and chronicity of back pain postulate a major impact of psychological factors in the process of back pain chronicity. PARTICIPANTS AND METHODS: Effects of gender and pain staging on rehabilitation outcome were examined immediately after and 3 and 6 months after rehabilitation in 121 patients with chronic low back pain (43 women, 78 men; M=48 years; ICD-10 diagnoses M54.4/M54.5). Pain was staged using the Mainz Pain Staging System. RESULTS: In the short and mid term, patients in stage I and women benefited from rehabilitation. Rehabilitation outcomes tended not to be improved for men in stage III. CONCLUSIONS: Results support the notion that rehabilitation outcome is significantly influenced by pain staging and gender. Thus, clinical-psychological and gender-specific interventions should be incorporated in future therapeutic regimens to increase the rehabilitation outcomes in patients with higher chronicity of back pain.

Amsacrine containing induction therapy in elderly AML patients: comparison to standard induction regimens in a matched-pair analysis.

Many elderly patients with newly diagnosed acute myeloid leukemia (AML) present with cardiac comorbidity precluding the use of anthracycline containing chemotherapy regimens. Amsacrine, a topoisomerase II inhibitor, has been proposed as possible alternative to anthracyclines. Here, we report about the combination of amsacrine (210 mg/m(2)), in replacement for daunorubicin (DNR), with standard dose cytarabine and thioguanine (TAA) to elderly patients (>or=60 years of age) with impaired cardiac function. The outcome of 16 patients with a median age of 66 years treated between 1997 and 2003 was compared with standard treatment regimens of the AMLCG study group in a matched-pair analysis. There were no statistically significant differences in response rate, relapse free survival or overall survival between TAA treated patients or standard therapy. In conclusion, replacing anthracyclines with amsacrine for induction therapy of AML patients with significant cardiac comorbidities represents a treatment option without compromising the potential curability of the disease.

Reduced intensity conditioning allows for up-front allogeneic hematopoietic stem cell transplantation after cytoreductive induction therapy in newly-diagnosed high-risk acute myeloid leukemia.

There is substantial need to improve the outcome of patients with high-risk acute myeloid leukemia (AML). The clinical trial reported here investigated a new approach of up-front allogeneic hematopoietic stem cell transplantation (HSCT), provided a median of 40 days (range 22-74) after diagnosis, in twenty-six consecutive patients with newly-diagnosed high-risk AML characterized by poor-risk cytogenetics (n = 19) or inadequate blast clearance by induction chemotherapy (IC, n = 7). The median age was 49 years (range 17-68). During IC-induced aplasia after the 1st (n = 11) or 2nd (n = 15) cycle, patients received allogeneic peripheral blood stem cells (PBSC) from related (n = 11) or unrelated (n = 15) donors following a fludarabine-based reduced-intensity regimen. Seventeen patients were not in remission before HSCT with a median marrow blast count of 34% (range 6-70). All patients achieved rapid engraftment and went into remission with complete myeloid and lymphatic chimerism. Grades II to IV acute GvHD occurred in 14 (56%) and extensive chronic GvHD was documented in 8 (35%) patients. The probability of disease-free survival was 61% with only three patients relapsing 5, 6 and 7 months after transplantation, respectively. Up-front allogeneic HSCT as part of primary induction therapy seems to be an effective strategy in high-risk AML patients and warrants further investigation.

High-frequency brain activity: its possible role in attention, perception and language processing.

Coherent high-frequency neuronal activity has been proposed as a physiological indicator of perceptual and higher cognitive processes. Some of these processes can only be investigated in humans and the use of non-invasive recording techniques appears to be a prerequisite for investigating their physiological substrate in the healthy human brain. After addressing methodological issues in the non-invasive recording of high-frequency responses, we summarize studies indicating co-occurrence of neuronal synchrony of single cells exhibiting rhythmic activity at high frequencies, oscillations in the local field potential and dynamics in high frequencies recorded using high-resolution electroencephalography (EEG) and magnetoencephalography (MEG). We then review EEG and MEG studies of attention, perception, and language processing in humans indicating that dynamics in the high-frequency range > 20 Hz reflect specific cognitive processes. Types of high-frequency (HF) activity can be distinguished according to their latency after stimulus onset, stimulus-locking, cortical topography and frequency. There appears to be a systematic relationship between specific cognitive processes and types of HF activity. The findings are related to recent theories about the generation of HF activity and their possible role in binding of stimulus features. Dynamics of HF cortical activity reflecting higher cognitive processes can be accounted for based on the assumption that the elements of cognitive processing, e.g. visual objects and words, are organized in the brain as distributed neuronal assemblies with defined cortical topographies generating well-timed spatio-temporal activity patterns.

Karyotype complexity and prognosis in acute myeloid leukemia.

A complex aberrant karyotype consisting of multiple unrelated cytogenetic abnormalities is associated with poor prognosis in patients with acute myeloid leukemia (AML). The European Leukemia Net classification and the UK Medical Research Council recommendation provide prognostic categories that differ in the definition of unbalanced aberrations as well as the number of single aberrations. The aim of this study on 3526 AML patients was to redefine and validate a cutoff for karyotype complexity in AML with regard to adverse prognosis. Our study demonstrated that (1) patients with a pure hyperdiploid karyotype have an adverse risk irrespective of the number of chromosomal gains, (2) patients with translocation t(9;11)(p21∼22;q23) have an intermediate risk independent of the number of additional aberrations, (3) patients with ⩾4 abnormalities have an adverse risk per se and (4) patients with three aberrations in the absence of abnormalities of strong influence (hyperdiploid karyotype, t(9;11)(p21∼22;q23), CBF-AML, unique adverse-risk aberrations) have borderline intermediate/adverse risk with a reduced overall survival compared with patients with a normal karyotype.

Individual patient data-based meta-analysis of patients aged 16 to 60 years with core binding factor acute myeloid leukemia: a survey of the German Acute Myeloid Leukemia Intergroup.

PURPOSE: To evaluate prognostic factors for relapse-free survival (RFS) and overall survival (OS) and to assess the impact of different postremission therapies in adult patients with core binding factor (CBF) acute myeloid leukemias (AML). PATIENTS AND METHODS: Individual patient data-based meta-analysis was performed on 392 adults (median age, 42 years; range, 16 to 60 years) with CBF AML (t(8;21), n = 191; inv(16), n = 201) treated between 1993 and 2002 in prospective German AML treatment trials. RESULTS: RFS was 60% and 58% and OS was 65% and 74% in the t(8;21) and inv(16) groups after 3 years, respectively. For postremission therapy, intention-to-treat analysis revealed no difference between intensive chemotherapy and autologous transplantation in the t(8;21) group and between chemotherapy, autologous, and allogeneic transplantation in the inv(16) group. In the t(8;21) group, significant prognostic variables for longer RFS and OS were lower WBC and higher platelet counts; loss of the Y chromosome in male patients was prognostic for shorter OS. In the inv(16) group, trisomy 22 was a significant prognostic variable for longer RFS. For patients who experienced relapse, second complete remission rate was significantly lower in patients with t(8;21), resulting in a significantly inferior survival duration after relapse compared with patients with inv(16). CONCLUSION: We provide novel prognostic factors for CBF AML and show that patients with t(8;21) who experience relapse have an inferior survival duration.

Comparison of spectral karyotyping and conventional cytogenetics in 39 patients with acute myeloid leukemia and myelodysplastic syndrome.

Spectral karyotyping (SKY) was performed in patients with acute myeloid leukemia (AML; n = 25), secondary AML (s-AML; n = 7), myelodysplastic syndrome (MDS; n = 6) and s-MDS (n = 1) to complement conventional cytogenetic investigations. According to the results of conventional cytogenetics the patients were subdivided into three groups: group 1, normal karyotype, n = 19 cases, median age = 64 years; group 2, patients displaying either one or two single aberrations, n = 10 cases, median age = 54 years; group 3, patients with > or =3 independent aberrations, n = 10 cases, median age = 61.5 years. SKY identified no abnormal metaphases in group 1. In one patient of group 2 a hidden translocation t(7;14)(q3?1;q2?2) could be revealed with SKY. Conventional cytogenetics had only shown trisomy 8. A similar t(7;14) was also detected in one patient of group 3. SKY was helpful for the delineation of marker chromosomes and additional material. Furthermore, SKY could distinguish between partial and total monosomies or real existing and apparent deletions. The combination of G-banding, FISH and SKY was found very useful for the precise delineation of the karyotype. As a result of our study we recommend SKY investigation as an important additional tool for accurate chromosome analysis. The detected t(7;14) might represent a novel recurrent translocation in acute myeloid leukemias.

Detection of cytogenetic aberrations both in CD90 (Thy-1)-positive and (Thy-1)-negative stem cell (CD34) subfractions of patients with acute and chronic myeloid leukemias.

Acute myeloid leukemia (AML) and chronic myeloid leukemia (CML) are thought to arise from malignant hematopoietic progenitor cells representing early and undifferentiated stem cell clones. In CML there is evidence for a progenitor cell subset free of leukemic clones, depending on the course of the disease. Additionally, it has been suggested that in AML, the early stem cell compartment (CD34+/90+) does not harbor the malignant clone. We analyzed white blood cells from leukemia patients for the presence of aberrant cells in stem cell subfractions. Sixteen patients with CML, six patients with AML, two patients with acute lymphatic leukemia (ALL) and one with chronic myelomonocytic leukemia (CMMOL), all with known cytogenetic abnormalities, were evaluated according to their CD90 (Thy-1)-positive or -negative phenotype. Subsets were sorted on to slides and further characterized by FISH and/or standard cytogenetic testing. The bcr-abl translocation or gross chromosomal abnormalities could be detected in equally high amounts of 92.2% and 89.2% in both stem cell subsets. We conclude, that in progressed AML and CML cells characterized by specific genetic aberrations implicated in the malignant state can be found in the CD34+/CD90+ and CD90- population, thus making CD90 an inappropriate marker to distinguish benign from malignant cells in these leukemias.

Sequential monitoring of chimerism and detection of minimal residual disease after allogeneic blood stem cell transplantation (BSCT) using multiplex PCR amplification of short tandem repeat-markers.

Sequential analysis of chimerism after allogeneic blood stem cell transplantation (BSCT) has been shown to be predictive for graft failure and relapse. We have explored the impact of a novel approach for the quantitative determination of chimerism using a commercial PCR assay with multiplex amplification of nine STR-loci and fluorescence detection. The feasibility was studied in 121 patients transplanted from related or unrelated donors. Follow-up investigation was performed in 88 patients. Twenty-eight of these patients had received a transplantation after dose-reduced conditioning therapy. Results were compared to data obtained by FISH analysis in a subgroup of patients receiving grafts from sex-mismatched donors. The analysis was possible in all patients, the median number of informative alleles was 4 (range 1-8) compared to 7 (range 1-9) in the related and unrelated situation, respectively. A good correlation was seen in 84 samples from 14 patients analyzed in parallel with STR-PCR and FISH. Decreasing values of donor chimerism were detected prior to or concomitantly with the occurrence of graft failure and relapse of disease in all patients investigated prospectively. Using FACS-sorted material, eg peripheral blood CD34+ cells, the assay permitted the detection of residual recipient cells with high sensitivity (down to one CD34+ Kasumi cell in 40,000 normal WBC). Evaluation of the inter-laboratory reproducibility revealed that in 20 samples analyzed in three different centers, the median coefficient of variation was 2.1% (range 0.7-9.6%). Taken together, the results support the use of the test as a valuable tool in the follow-up of patients undergoing allogeneic BSCT. In cases lacking PCR-detectable disease-specific gene products, this assay may represent an alternative to recently established real-time PCR methods.

Evolution of vectorcardiographic QRS changes during myocardial infarction in dogs and their relation to infarct size.

The ability of vectorcardiographic QRS changes to quantify myocardial ischaemia and necrosis in dogs was studied. Myocardial infarction was produced in 21 anaesthetised dogs by inflating a balloon inserted into the right, left anterior descending, or left circumflex coronary artery. A Frank vectorcardiogram was recorded before and every 15-30 minutes for 10 hours after the occlusion. ST vector magnitude (ST-VM), QRS summation vectors, and QRS integral differences (QRS-VD) between the preocclusion recording and subsequent recordings were computed. Twenty four hours after occlusion two vectorcardiograms were obtained, the hearts removed, and the infarcts cut out and weighed. Four dogs were excluded from the study because of persistent arrhythmias, major conduction defects, or sudden death. In the remaining 17 dogs the QRS summation vectors rotated maximally towards the site of infarction 7 minutes after occlusion corresponding to a median minimum QRS-VD of -19 (range -2 to -29) microVs. This coincided with the maximum ST-VM, median 0.43 (range 0.12-0.68) mV. The QRS summation vectors subsequently rotated away from the infarct producing a median maximum QRS-VD of 20 (range 6-28) microVs. The maximum QRS-VD correlated significantly with the percentage of infarcted myocardium (r = 0.82). The correlation between the early minimum QRS-VD and the maximum ST-VM was r = 0.83. The QRS-VD was recomputed with a reference taken 2 or 4 hours after occlusion. The relation between maximum QRS-VD and infarct percentage was not significantly changed with the reference at 2 hours, but with the reference at 4 hours the ability to predict infarct size was lost.(ABSTRACT TRUNCATED AT 250 WORDS)

Hematopoietic cell transplantation in patients with intermediate and high-risk AML: results from the randomized Study Alliance Leukemia (SAL) AML 2003 trial.

The optimal timing of allogeneic hematopoietic stem cell transplantation (HCT) in acute myeloid leukemia (AML) is controversial. We report on 1179 patients with a median age of 48 years who were randomized upfront. In the control arm, sibling HCT was scheduled in the first complete remission for intermediate-risk or high-risk AML and matched unrelated HCT in complex karyotype AML. In the experimental arm, matched unrelated HCT in first remission was offered also to patients with an FLT3-ITD (FMS-like tyrosine kinase 3-internal tandem duplication) allelic ratio >0.8, poor day +15 marrow blast clearance and adverse karyotypes. Further, allogeneic HCT was recommended in high-risk AML to be performed in aplasia after induction chemotherapy. In the intent-to-treat (ITT) analysis, superiority of the experimental transplant strategy could not be shown with respect to overall survival (OS) or event-free survival. As-treated analyses suggest a profound effect of allogeneic HCT on OS (HR 0.73; P=0.002) and event-free survival (HR 0.67; P<0.001). In high-risk patients, OS was significantly improved after allogeneic HCT in aplasia (HR 0.64; P=0.046) and after HCT in remission (HR 0.74; P=0.03). Although superiority of one study arm could not be demonstrated in the ITT analysis, secondary analyses suggest that early allogeneic HCT is a promising strategy for patients with high-risk AML.

The concept of transcortical cell assemblies: a key to the understanding of cortical lateralization and interhemispheric interaction.

According to Hebb, elements of higher cognitive processes, such as concepts, words and mental images, are realized in the brain as cortical cell assemblies, i.e. large and strongly connected neuron populations that form functional units. Neurons belonging to such assemblies may be scattered over wide cortical areas, and some cell assemblies may even comprise neurons of both hemispheres (transcortical assemblies). If full activation (ignition) of an assembly leads to fast circulation of neuronal activity in the assembly, this process should be visible in high-frequency cortical responses. Some evidence will be reviewed that cell assembly ignition indeed leads to changes in high-frequency cortical responses which can be recorded in the EEG and MEG. Within the cell assembly-framework, the question of cortical laterality translates into the question of how neurons of transcortical assemblies are balanced between the hemispheres. This approach allows for different degrees of laterality. Recent evidence is summarized that the degree of laterality indeed differs between language units. For example, the cortical representation of certain words appears to be strongly lateralized to the left hemisphere while those of others are less lateralized. If neurons of both hemispheres are part of one assembly bihemispheric processing should lead to a processing advantage compared to processing in the dominant hemisphere alone. The latter appears to be the case for lexical processing, as revealed by recent behavioral studies. In conclusion, the cell assembly-framework suggests a more fine-grained description of the issue of cortical laterality; it is not appropriate to ask whether "modules" supporting higher cortical functions are located either in the left or right hemisphere. Rather, it appears fruitful to ask how the neurons of transcortical cell assemblies are balanced between the hemispheres.

Constraint-induced therapy of chronic aphasia after stroke.

Patients with chronic aphasia were assigned randomly to a group to receive either conventional aphasia therapy or constraint-induced (CI) aphasia therapy, a new therapeutic technique requiring intense practice over a relatively short period of consecutive days. CI aphasia therapy is realized in a communicative therapeutic environment constraining patients to practice systematically speech acts with which they have difficulty. Patients in both groups received the same amount of treatment (30 to 35 hours) as 10 days of massed-practice language exercises for the CI aphasia therapy group (3 hours per day minimum; 10 patients) or over a longer period of approximately 4 weeks for the conventional therapy group (7 patients). CI aphasia therapy led to significant and pronounced improvements on several standard clinical tests, on self-ratings, and on blinded-observer ratings of the patients' communicative effectiveness in everyday life. Patients who received the control intervention failed to achieve comparable improvements. Data suggest that the language skills of patients with chronic aphasia can be improved in a short period by use of an appropriate massed-practice technique that focuses on the patients' communicative needs.

Altered hemispheric asymmetry of auditory magnetic fields to tones and syllables in schizophrenia.

BACKGROUND: A growing body of literature suggests that schizophrenic patients often do not show the normal brain hemispheric asymmetry. We have found this for simple tones presented to the right ear in a previous study. In this study we extended this investigation to left ear stimulation and verbal stimuli. METHODS: With a whole-head neuromagnetometer, contra- and ipsilateral auditory-evoked magnetic fields in response to tones (1000 Hz) and to the syllables ("ba") delivered to the left and right ears in separate runs were compared between schizophrenic patients (n = 17) and healthy control subjects (n = 15). RESULTS: In response to tones, all control subjects showed the expected asymmetry (contralateral predominance) of the auditory-evoked magnetic N100m (dipole moment). In the patient sample asymmetry was reversed following tones presented to the left ear in 47% and following tones to the right ear in 24%. In response to syllables, the asymmetry was similar between groups. In patients compared with control subjects the N100m was located more anterior without asymmetry between hemispheres. CONCLUSIONS: Results suggest that deviation from the normal functional lateralization in schizophrenia appears in a proportion of patients at a basic stage of auditory processing, but may be compensated for at higher levels such as the processing of syllables.

Lexical decision after left, right and bilateral presentation of function words, content words and non-words: evidence for interhemispheric interaction.

Function words, content words and pronounceable non-words (pseudowords) were presented tachistoscopically either in the left or the right visual field or with identical copies flashed simultaneously to both visual half-fields. Consistent with earlier studies [10], function words were found to show a right visual field advantage, whereas for content words the right visual field advantage was absent. Compared to either of the unilateral modes of presentation, bilateral presentation of identical word stimuli improved accuracy and latency significantly. The bilateral (Bi) advantage was largest for content words, and was also highly significant for function words in both latency and accuracy. The Bi gain was absent for non-words (significant interaction of Wordness x Visual Field). These results indicate that the lexicons of the left and right hemisphere can "collaborate" rather than inhibit each other or act independently when processing the same linguistic stimuli. Our findings are consistent with the view that the neuronal counterparts of words are Hebbian cell assemblies consisting of strongly connected excitatory neurons of both hemispheres. Since function words show a right visual field advantage in addition to their Bi gain, their assemblies are likely to have most of their neurons located in the left hemisphere. Neuronal assemblies corresponding to content words may be less strongly lateralized.

Multiple simultaneous stimulus presentation facilitates lexical processing.

Bilateral presentation of two copies of the same word leads to faster lexical decisions compared to unilateral presentation alone (bilateral gain). This has implications for theories of interhemispheric interaction, because it suggests that, under certain conditions, both hemispheres cooperate rather than inhibit each other or act independently. Experiment 1 confirmed that the bilateral gain is word-specific and does not occur for pseudowords. Whereas the bilateral gain proved to be present for words of different word frequencies, results of Experiment 2 suggest that it is slightly stronger for high-frequency words compared to words of lower frequencies. Experiment 3 revealed that higher numbers of stimuli (two versus four copies of the same word/pseudoword) presented at the same time lead to an additional improvement of word processing. These results support a neurobiological model of word representation assuming that words are cortically represented in widely distributed interhemispheric cell assemblies. Summation of activity in such assemblies leads to faster and more reliable ignition of the network.

Echocardiographic and clinical spectrum of mitral anular calcification.

To establish the reliability of echocardiography in making the diagnosis of mitral anular calcification 10 consecutive patients with dense echoes at the mitral anular area were examined fluoroscopically, using an image intensifier. Nine of these had distinct mitral anular calcification. The echocardiographic reliability thus confirmed, 30 cases with similar findings were reviewed and the total group of 40 cases were used to define the echocardiographic spectrum of mitral anular calcification. This lesion extended variably from the anulus to involve the posterior left ventricular wall, mitral valve leaflets, aortic root, aortic valve and interventricular septum. The pleomorphic echocardiographic findings introduce difficulties in the diagnosis of pericardial effusion and mitral stenosis. Echocardiography is a reliable method of diagnosing mitral anular calcification, but care must be taken to avoid confusing this condition with others it resembles.