Aneuploidy and percentage of S-phase cells determined by flow cytometry correlate with cell phenotype in childhood acute leukemia

Cellular DNA content distributions of propidium-iodide-stained bone marrow blasts were determined by flow cytometry (FCM) for 225 untreated children with acute leukemia and were correlated with leukemia cell phenotype and karyotype. Aneuploidy of the primary malignant stem line was detected in 54 cases (24%): 51 hyperdiploid and 3 hypodiploid. A second stem line with approximately twice the DNA content of the primary stem line was recognized by FCM in 28 cases (23 ALL, 5 ANLL) and may be an important source of leukemia cell heterogeneity. The degree of DNA content abnormality detected by FCM was highly correlated (r = 0.98) with the number of whole chromosome gains or losses in the leukemia karyotype. Aneuploidy detectable by FCM was more frequent in acute lymphoblastic leukemia (ALL) (52 of 173, 30.1%) than in acute nonlymphoblastic leukemia (2 of 52, 3.8%) (p less than 0.001). In the ALL group, aneuploidy was significantly correlated with the cell surface expression of common ALL antigen: 46 of 127 antigen-positive cases were aneuploid compared to 6 of 46 antigen-negative cases (p less than 0.003). Only 2 of 21 cases of T-cell ALL without common ALL antigen had detectable aneuploidy, which was significantly less than in the common ALL group (p = 0.02). The median percentage of cells in S- phase was significantly greater for B-cell and erythrocyte rosette- positive T-cell ALL, than for the other phenotypic subgroups. We conclude that aneuploidy and S-phase cell percentage are correlated with the state of leukemia cell differentiation. The biologic basis for the correlation is not established, but may be linked to the process of malignant transformation.     

Recognition of actual periods of nocturnal rest from 24-hour heart rate profile

Inability to delineate exactly periods of nocturnal sleep and diurnal wakefulness during 24-hour blood pressure (BP) monitoring causes reporting of erroneous BP values for these periods. We suggested a simple mathematical algorithm for detection of periods of nocturnal rest determined as period of low values of cardiac rhythm using data of BP monitoring itself. AIM: To compare novel method of recognition of periods of sleep with 2 standard techniques: use of fixed time interval between 23 and 7 hours (1), or period of sleep according to patient's diaries (2). Reproducibility of nocturnal BP lowering between two 24-hour intervals during 48-hour blood pressure monitoring was used as a measure of precision of determination of diurnal/nocturnal BP. METHODS: Ambulatory 48-hour BP monitoring was carried out in 33 patients with uncomplicated stage II hypertensive disease. Automatic analysis of BP monitoring data was performed with the use of specially designed computer application. Standard deviation (SD) of differences (SDD) between pairs of nocturnal BP lowering during 48 hours was used as a measure of reproducibility. RESULTS: Reproducibility of values obtained with novel algorithm (SDD for systolic/diastolic BP 6.7/8.2 mm Hg) was substantially better than those obtained with standard methods (1) and (2) (SDD 13.0/14.8 and 13.5/18.3 mm Hg, respectively). CONCLUSION: The proposed method of recognition of the period of nocturnal rest substantially improved precision of automatic analysis of 24-hour BP monitoring.     

Association Study Indicates a Protective Role of Phosphatidylinositol-4-Phosphate-5-Kinase against Tardive Dyskinesia

Background:

Tardive dyskinesia is a disorder characterized by involuntary muscle movements that occur as a complication of long-term treatment with antipsychotic drugs. It has been suggested to be related to a malfunctioning of the indirect pathway of the motor part of the cortical-striatal-thalamic-cortical circuit, which may be caused by oxidative stress-induced neurotoxicity.

Methods:

The purpose of our study was to investigate the possible association between phosphatidylinositol-4-phosphate-5-kinase type IIa (PIP5K2A) function and tardive dyskinesia in 491 Caucasian patients with schizophrenia from 3 different psychiatric institutes in West Siberia. The Abnormal Involuntary Movement Scale was used to assess tardive dyskinesia. Individuals were genotyped for 3 single nucleotide polymorphisms in PIP5K2A gene: rs10828317, rs746203, and rs8341.

Results:

A significant association was established between the functional mutation N251S-polymorphism of the PIP5K2A gene (rs10828317) and tardive dyskinesia, while the other 2 examined nonfunctional single nucleotide polymorphisms were not related.

Conclusions:

We conclude from this association that PIP5K2A is possibly involved in a mechanism protecting against tardive dyskinesia-inducing neurotoxicity. This corresponds to our hypothesis that tardive dyskinesia is related to neurotoxicity at striatal indirect pathway medium-sized spiny neurons.     

Clinical significance of low levels of myeloperoxidase positivity in childhood acute nonlymphoblastic leukemia

The clinical significance of a low percentage of myeloperoxidase- positive blast cells in childhood acute nonlymphoblastic leukemia was determined. Of 155 consecutive cases studied by cytochemical staining methods, 14 were characterized by 4% to 15% (median 6%) myeloperoxidase- positive blasts. All 14 cases showed reactivity to Sudan black B stain, and 7 had Auer rods. The morphological subtypes of leukemia were M1 (8 cases), M2 (3), M4 (1), and M5 (2). Immunological marker studies disclosed the lymphoid-associated T11 antigen on cells from 8 of the 11 cases tested. Other lymphoid-related findings in these 8 cases included the T3 antigen and E rosette formation in 1 case each. Among cases that were prospectively studied for the expression of lymphoid-associated markers, 6 of 8 with low levels of myeloperoxidase positivity compared with only 1 of 44 with higher levels (greater than 15%) possessed such features (P less than 0.001). We conclude that low levels of myeloperoxidase reactivity distinguish cases of acute leukemia in which the blast cells coexpress lymphoid (T11 antigen) and myeloid markers.     

Biplane stereoscopic magnification cerebral angiography

An angiographic system capable of simultaneous biplane stereoscopic magnification cerebral angiography was evaluated. Stereoscopic imaging improved the morphologic depiction of aneurysms and of arteriovenous malformations. In a series of 357 patients, procedure time was reduced because the initial biplane stereoscopic series was nearly always diagnostic, obviating the need for additional angiographic views.     

Targeted screening for diabetes in community chiropody clinics

Population screening for diabetes mellitus is of uncertain value. We therefore assessed the value of screening amongst community chiropody clinic attenders in Liverpool. All attenders aged between 40 and 75 years during a 3-month period were offered screening by urine glucose self-testing, 2 hours post-prandially, backed up with glucose tolerance tests (GTT) for positive respondents. Of 1058 patients screened, 11 (1.0%) reported positive results, of whom four (0.4% of total) had diabetes, and two had impaired glucose tolerance (IGT). Screening costs were 11p per person, 2.06 pounds per 'positive' person, and 34.46 pounds for each newly diagnosed patient. The screening procedure was simple and highly cost-effective, but the diagnostic returns were only moderate. This may have been because of a high rate of known diabetes amongst the chiropody clinic attenders (17.3%). In view of this, routine widespread diabetes screening in chiropody clinics cannot at present be recommended.      

Recurrent recurrent gallstone ileus

We describe the second reported case of three consecutive episodes of gallstone ileus and ask the question whether recurrent gallstone ileus justifies definitive surgery to the fistula itself or can be safely managed by repeated enterotomies.