Molecular follow-up of disease progression and interferon therapy in chronic myelocytic leukemia

We previously reported that the abl promoter (Pa) undergoes de novo DNA methylation in the course of chronic myelocytic leukemia (CML). The clinical implications of this finding are the subject of the present study in which samples of CML patients, including a group treated with interferon alpha (IFNalpha) were surveyed. The methylation status of the abl promoter was monitored by polymerase chain reaction (PCR) amplification of the Pa region after digestion with several site-methylation sensitive restriction enzymes. Some 74% of the DNA samples from blood and marrow drawn in the chronic phase were nonmethylated, similar to control samples from non-CML patients. The remaining 26% were partially methylated in the abl Pa region. The latter samples were derived from patients who were indistinguishable from the others on the basis of clinical presentation. Methylated samples were mostly derived from patients known to have a disease of longer duration (26 months v 7.5 months, P = .01). Samples of 30 IFNalpha-treated patients were sequentially analyzed in the course of treatment. Fifteen patients with no evidence of Pa methylation before treatment remained methylation-free. The remainder, who displayed Pa methylation before treatment, reverted to the methylation-free status. The outcome is attributed to IFNalpha therapy, as the Pa methylation status was not reversed in any of the patients treated with hydroxyurea. Methylation of the abl promoter indicates a disease of long-standing, most likely associated with a higher probability of imminent blastic transformation. It appears to predict the outcome of IFNalpha therapy far better than the cytogenetic response.     

Bone mineral density and survival of elements and element portions in the bones of the Crow Creek massacre victims

The interpretation of archaeologically-derived skeletal series is dependent on the elements and portions of elements preserved for examination. Bone and bone portion survival is affected by factors, both intrinsic and extrinsic to the elements themselves, that influence deterioration and preservation. Among the intrinsic variables, the density of the element and element portion are particularly important with respect to the degree of preservation. Recently reported bone mineral density values from a contemporary human sample are compared to the survival of prehistoric limb bones of the Crow Creek specimens, a fourteenth-century massacre skeletal series. The contemporary density values are positively correlated with Crow Creek element and element portion survival. Two calculations of bone mineral density, however, are more closely related to preservation than a third. Such density information has implications for assessing minimum number of elements and individuals and documenting taphonomic processes.     

The arterioportal fistula syndrome: clinicopathologic features, diagnosis, and therapy

BACKGROUND & AIMS: Arterioportal fistulas (APFs) are rare vascular disorders of the mesenteric circulation. The aim of this study was to determine the etiology, anatomical location, and main symptom at presentation of APFs, and analyze the various modes of treatment. METHODS: The etiology, clinical presentation, radiographs, and treatment of 12 patients with APFs are reported in detail, and another 76 cases published since 1980 are reviewed. RESULTS: APFs result from trauma (n = 25, 28%), iatrogenic procedures (n = 14, 16%), congenital vascular malformations (n = 13, 15%), tumor (n = 13, 15%), aneurysm (n = 12, 14%), and other causes (n = 11, 12%). The origin of APFs is the hepatic artery in the majority of patients (n = 56, 65%). The main symptoms at presentation are lower or upper gastrointestinal bleeding (n = 29, 33%), ascites (n = 23, 26%), heart failure (n = 4.5%), or diarrhea (n = 4.5%). Radiological intervention provides definitive treatment in 42% (n = 33) of patients, whereas the remainder are treated by surgery alone (n = 27, 31%) or a combination of radiological intervention and surgery (n = 8, 9%). CONCLUSIONS: APFs result in a protean syndrome variously combining portal hypertension and other hemodynamic imbalances (heart failure, intestinal ischemia). Single or multiple interventional radiological procedures using arterial and/or venous approaches allow definitive treatment of most APFs. With increasing technological advances, it is anticipated that surgery will only be indicated in rare instances after failure of radiological intervention(s).     

The progression of chronic renal disease: immunological, nutritional and intrinsic renal mechanisms

The majority of patients with any initial renal insult show progression of renal damage over time. The histological end-result is often the same, whatever the initial lesion, and consists of an increase in extracellular matrix (ECM) and ultimately glomerulosclerosis. The clinical rate of progression correlates mainly with the degree of interstitial, rather than with that of glomerular damage. The main culprits for the ultimate interstitial damage and the rate of progression of renal disease, are the type and degree of the initial (e.g. immunological) insult and the magnitude of the proteinuria. Hypertension (intraglomerular) is an independent risk factor. Control of hypertension with angiotension converting enzyme (ACE) inhibitors or angiotensin II (AII) receptor blockers, reduction of protein and fat intake, anti-oxidative therapy and a variety of experimental measures reduce the progression of renal damage in animal experiments. Some of these interventions have also been shown to be beneficial in a number of controlled clinical studies, in well-defined renal disease entities in humans. These new data provide insight into the pathogenesis of chronic renal damage and raise the hope that in the not too far future, effective strategies can be devised to attenuate the progression of acquired renal disease.     

HoxA is a transcriptional regulator for expression of the hup structural genes in free-living Bradyrhizobium japonicum

A chromosomally integrated Bradyrhizobium japonicum hoxA mutant is unable to oxidize hydrogen in free-living conditions. Derepressing conditions that induce hydrogenase activity in free-living, wild-type B. japonicum cells cannot induce expression of the hydrogenase structural genes in the hoxA mutant. The DNA-binding capacity of HoxA at the hup promoter region was studied by means of gel retardation. Both heterotrophically growing cells and cells induced to express hydrogenase activity contain a protein that specifically binds to the hup promoter region. Crude protein extracts isolated from a B. japonicum hoxA mutant do not contain this binding compound. The HoxA protein was overexpressed in E. coli and isolated in the form of a maltose-binding protein (MBP)-HoxA fusion. The MBP-HoxA hybrid protein specifically bound to a 50 bp region of the hupSL promoter known to be important for regulation of hupSL expression.     

CO2 laser surgery in osteomyelitis

Spirituality is a critical component of the holistic mind-body-spirit model embraced by Hospice. Hospice chaplains, as part of the caregiving team, must understand their abilities and limitations in providing spiritual guidance to others who may differ in religious and spiritual beliefs.     

Characterization of aluminum hydroxide particles from the Bayerprocess using neural network and Bayesian classifiers

An automatic process of isolating and characterizing individual aluminum hydroxide particles from the Bayer process in scanning electron microscope gray-scale images of samples is described. It uses image processing algorithms, neural nets and Bayesian classifiers. As the particles are amorphous and different greatly, there were complex nonlinear decisions and anomalies. The process is in two stages; isolation of particles, and classification of each particle. The isolation process correctly identifies 96.9% of the objects as complete and single particles after a 15.5% rejection of questionable objects. The sample set had a possible 2455 particles taken from 384 256x256-pixel images. Of the 15.5%, 14.2% were correctly rejected. With no rejection the accuracy drops to 91.8% which represents the accuracy of the isolation process alone. The isolated particles are classified by shape, single crystal protrusions, texture, crystal size, and agglomeration. The particle samples were preclassified by a human expert and the data were used to train the five classifiers to embody the expert knowledge. The system was designed to be used as a research tool to determine and study relationships between particle properties and plant parameters in the production of smelting grade alumina by the Bayer process.     

The cross product of interconnection networks

We study the cross product as a method for generating and analyzing interconnection network topologies for multiprocessor systems. Consider two interconnection graphs G₁ and G₂ each with some established properties such as symmetry, low degree and diameter, scalability, simple optimal routing, recursive structure (partitionability), fault tolerance, existence of node-disjoint paths, low cost embedding, and efficient broadcasting. We investigate and evaluate the corresponding properties for the cross product of G₁ and G₂ based on the properties of G₁ and those of G₂. We also give a mathematical characterization of product families of graphs which are closed under the cross product operation. This investigation is useful in two ways. On one hand, it gives a new tool for further studying some of the known interconnection topologies, such as the hypercube and the mesh, which can be defined using the cross product operation. On the other hand, it can be used in defining and evaluating new interconnection graphs using the cross product operation on known topologies     

Single-dose versus multiple instillations of epirubicin as prophylaxis for recurrence after transurethral resection of pTa and pT1 transitional-cell bladder tumours: a prospective, randomized controlled study

OBJECTIVE: To compare single-dose and multiple instillations of epirubicin in the chemoprophylaxis of superficial bladder tumours. PATIENTS AND METHODS: In a prospective randomized and controlled study, 168 evaluable patients were assigned to three groups after transurethral resection of bladder tumour (TURBT) and histological confirmation of its superficial nature (pTa and pT1). The groups were comparable for tumour stage, grade and other tumour characteristics. In group 1, patients received a single dose of 50 mg epirubicin in 50 mL normal saline immediately after TURBT; group 2 received 50 mg epirubicin in 50 mL normal saline 1-2 weeks after TURBT and the instillations were repeated for 8 weeks and thereafter monthly to complete one year of treatment: group 3 (control group) received no adjuvant therapy after TURBT. The patients were assessed by cysto-urethroscopy, urine cytology and DNA flow cytometry 8 weeks after resection and then every 3 months during the first 2 years and 6 monthly thereafter during the next 2 years. Intravenous urography was performed annually and when otherwise indicated. RESULTS: The recurrence rate was significantly lower in the patients treated with epirubicin than in the control group (24, 25 and 52%, respectively; P < 0.001). In those receiving epirubicin, the rates of recurrence were statistically comparable (P = 0.9). Patients who had a large tumour burden showed slightly lower recurrence rates with single-dose epirubicin than with delayed maintenance therapy but the difference was statistically insignificant. Patients with a history of bladder tumours before treatment had lower recurrence rates with maintenance treatment than with a single dose (34.6 and 22.6% in groups 1 and 2, respectively); again this difference was statistically insignificant. Patients with grade 3 tumours showed a marginal difference in favour of maintenance therapy. The rates of progression amongst the three groups were 5.5, 3.4 and 9.3%, respectively, with no significant differences. The overall toxicity rates were comparable in the two treated groups (22 and 25%). CONCLUSION: With the possible exception of grade 3 tumours, single-dose immediate epirubicin is as effective as delayed maintenance therapy, with the advantage of being more cost-effective.