The role of prognostic factors in treatment selection for early-stage Hodgkin's disease

PURPOSE: To identify poor prognostic factors in early-stage Hodgkin's disease that predict a high rate of relapse after radiotherapy alone. MATERIALS AND METHODS: A total of 153 patients with stages I and II supradiaphragmatic Hodgkin's disease, treated between 1964 and 1986 with either radiotherapy alone (120 patients) or combined modality therapy (33 patients), were studied retrospectively to determine factors affecting freedom from relapse and absolute survival. Median follow-up was 13 years. Clinical factors were assessed by the stepwise use of a stratified log-rank test and included maximum tumor dimension in any site (< or = 6 cm or > 6 cm), age (< or = 40 or > 40), presence or absence of B symptoms, pathologic and clinical stages (I or II), number of sites involved (< or = 4 or > 4), gender, histologic subtype, and large mediastinal mass (none, small [< or = 6 cm], large [> 6 cm]). RESULTS: The only factors independently predicting a high rate of relapse were tumor dimension (> 6 cm) and number of sites (> 4 sites). At 10 years, in patients with and without the two poor prognostic factors treated with radiotherapy alone, the freedom from relapse rates were 53% and 84% (p < .0001) and the absolute survival rates were 72% and 85% (p = .004), respectively. Combined modality therapy significantly improved freedom from relapse, but not absolute survival, in patients with one or both poor prognostic factors. CONCLUSIONS: Two poor prognostic factors were identified that were highly significant in predicting a high risk of relapse after radiotherapy alone. The addition of three cycles of chemotherapy to standard radiotherapy significantly reduced the relapse rate in high-risk patients.     

gamma-Aminobutyric acid type A receptors in the rat brain can contain both gamma 2 and gamma 3 subunits, but gamma 1 does not exist in combination with another gamma subunit

Antibodies specific for the gamma 1, gamma 2, and gamma 3 subunits of the gamma-aminobutyric acid (GABA)A receptor have been used to probe the composition of naturally occurring GABAA receptors in the rat brain. Most GABAA receptors contain at least one of these three subunits. The percentage of each, determined by immunoprecipitation of [3H]muscimol binding, was 11 +/- 1%, 59 +/- 3%, and 14 +/- 2% for gamma 1, gamma 2, and gamma 3 subunits, respectively. Receptors containing gamma 2 or gamma 3 subunits were labeled by benzodiazepine site ligands with high affinity, whereas gamma 1-containing receptors could be labeled only by [3H]muscimol. Receptors immunoprecipitated by anti-gamma 2 or anti-gamma 3 antibodies were labeled with [3H]Ro 15-1788 with similar affinities (Kd for anti-gamma 2-immunoprecipitated receptors, 1.9 nM; Kd for anti-gamma 3-immunoprecipitated receptors, 1.7 nM). Immunoprecipitation or Western blot analysis of GABAA receptors solubilized from rat cerebellar or whole-brain preparations indicated that gamma 1 was not present coassembled with any other gamma subunit. Western blot analysis of receptors purified on alpha-specific immunoaffinity resins showed that gamma 1 was predominantly assembled with the alpha 2 subunit. Some GABAA receptors may contain more than one type of gamma subunit. Quantitative immunoprecipitation and Western blot analysis both indicated that gamma 2 and gamma 3 subunits can exist in the same receptor complex. A large proportion of GABAA receptors immunopurified on a gamma 3 affinity resin also appeared to contain a gamma 2 subunit. In contrast, when receptors were purified on a gamma 2 affinity resin a small proportion also appeared to contain a gamma 3 subunit. We conclude that most gamma 1-containing receptors have no other gamma subunit in the same receptor complex but some GABAA receptors contain both gamma 2 and gamma 3 subunits.     

Inclusion body myositis: clinical and pathological boundaries

Inclusion body myositis, polymyositis, and dermatomyositis are three distinct categories of inflammatory myopathy. Some authorities commented on the selective early weakness of the volar forearm muscles, quadriceps, and ankle dorsiflexors in inclusion body myositis. The most important feature distinguishing inclusion body myositis from the other two inflammatory myopathies is the lack of responsiveness to immunosuppressive treatment. Although most patients with inclusion body myositis have characteristic muscle biopsy findings, some cannot be distinguished histologically early from polymyositis. Predicting responsiveness to immunosuppressive medications, independent of muscle histology, would be valuable to clinicians. We retrospectively reviewed the pattern of weakness and other clinical features of 46 patients newly diagnosed with either inclusion body myositis, polymyositis, or dermatomyositis. Asymmetrical muscle weakness with prominent wrist flexor, finger flexor, and knee extensor involvement was specific for inclusion body myositis and unresponsive polymyositis. Male sex, lower creatine kinase levels, slower rate of progression, and peripheral neuropathy were also more common in inclusion body myositis and unresponsive polymyositis than in responsive polymyositis and dermatomyositis patients. Repeat muscle biopsy in 2 patients in the unresponsive polymyositis group demonstrated histological features of inclusion body myositis. We suspect that patients with clinical features of inclusion body myositis but lacking histological confirmation may nonetheless have inclusion body myositis. Our study supports the recently proposed criteria for definite and possible inclusion body myositis.     

Congenital urethral strictures

We present 12 patients with presumed congenital urethral stricture (mean age at diagnosis 20 years). They complained of various urological symptoms, including dysuria, transient urinary retention, urgency and reduced flow. The time from onset of symptoms to diagnosis averaged 18 months. The strictures were presumed congenital because no patient had a history of urethral infection or of instrumentation, and all the strictures were at the proximal bulbar urethra, as has been described for congenital, bulbar, urethral stricture. We treated 5 patients initially by internal urethrotomy, of whom 2 required transurethral dilatation at follow-up. 7 others were treated initially by transurethral dilatation, 4 of whom required more than 1 treatment. Follow-up has averaged 21 months. In 8 of 10 patients the maximal urinary flow at latest follow-up is greater than 20 ml/sec.     

Inhibition of peripheral blood mononuclear cell proliferation by cardiac glycosides

We prospectively studied the epidemiologic, clinic signs and outcome of bacterial meningitis in 125 children who were admitted into a PICU (Pediatric Intensive Care Unit) of 11 hospitals of Spain and whose meningitis was diagnosed between May 1994 and April 1995. RESULTS: The median age of the children was 3.55 +/- 3.32 years (range 1 month to 16.5 yrs). Eighty-eight were bacterial meningitis, probably bacterial 30 and aseptic 7. The most frequently isolated organisms were N. meningitidis (52), H. influenza type b (17) and S. pneumoniae (8). Twenty-five percent of N. meningitidis had C serotype. Incidence rate of each germen was depending of age. All patients diagnosed of H. influenza type b meningitis were less than 3 years old. H. influenza type b and meningococcus had similar incidence rate during the first year of life (27% versus 31%). During the first three years of life H. influenza type b produced one third of bacterial meningitis. A mortality rate of 5.6% (seven patients: 3 S. pneumoniae, 1 N. meningitidis, 1 H. influenza type b and 2 unknown germen) was observed. Patients who die had lower Glasgow coma score (p = 0.034) and seizures (p = 0.001) at admission. At discharge of PICU, 9 survivors (7.2%) had sequelae: mental retardation in 7 patients and hearing loss in two. One third of patients needed hemodynamic support and a 15% of them ventilatory support. CONCLUSIONS: Age is an important epidemiological factor in the etiology of pediatric acute meningitis. H. influenza type b and N. meningitidis had similar incidence rate during the first year of life. S. pneumoniae had the highest mortality rate (37.5%). The presence of coma and seizures at admission were associated with mortality.     

Sue Rosenberg Zalk (1945-2001).

Memorializes developmental psychologist Sue R. Zalk. Her contributions to the field of education and the study gender are discussed. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

SUBJECTIVE CERAMIC MACHINABILITY AND MATERIAL PROPERTIES

Nine different ceramic materials were subjectively evaluated, on a scale from 1 to 100, for machinability by experienced machinists. The property values of hardness, fracture toughness and elastic modulus were also obtained for the materials. Correlations were sought between the material properties and subjective machinability results. A grindability parameter and a model predicting material removal rates were included in the correlation analyses. Trends were noted between the subjective machinability evaluations and both hardness and grindability, although the grindability parameter did not correlate with either hardness or the material removal rate model.     

Scalable solutions to integral-equation and finite-elementsimulations

When developing numerical methods, or applying them to the simulation and design of engineering components, it inevitably becomes necessary to examine the scaling of the method with a problem's electrical size. The scaling results from the original mathematical development; for example, a dense system of equations in the solution of integral equations, as well as the specific numerical implementation. Scaling of the numerical implementation depends upon many factors; for example, direct or iterative methods for solution of the linear system, as well as the computer architecture used in the simulation. Scalability is divided into two components-scalability of the numerical algorithm specifically on parallel computer systems and algorithm or sequential scalability. The sequential implementation and scaling is initially presented, with the parallel implementation following. This progression is meant to illustrate the differences in using current parallel platforms and sequential machines and the resulting savings. Time to solution (wall-clock time) for differing problem sizes are the key parameters plotted or tabulated. Sequential and parallel scalability of time harmonic surface integral equation forms and the finite-element solution to the partial differential equations are considered in detail     

Effect of valued activity disability, social comparisons, and satisfaction with ability on depressive symptoms in rheumatoid arthritis.

This longitudinal study identified a model through which function affects the psychological well-being of individuals with rheumatoid arthritis (RA). Results of hierarchical linear regression analyses (N = 436) demonstrated that greater physical impairment resulted in greater disability in valued activities and engagement in unfavorable social comparisons. All 3 factors--greater physical impairment, greater disability in valued activities, and unfavorable comparison evaluations--predicted low satisfaction with abilities. Low satisfaction with abilities was the most important predictor of higher depressive symptoms and mediated the impact of physical impairment, valued activity disability, and unfavorable comparisons on depressive symptoms. Results highlight the role of personal meaning attached to changes in functional status in predicting the long-term psychological well-being of individuals with chronic illnesses such as RA. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Cytotoxicity of a series of mono- and di-substituted thiourea in freshly isolated rat hepatocytes: a preliminary structure-toxicity relationship study

The cytotoxicity of a series of 12 mono- and 4 di-substituted thiourea containing compounds in freshly isolated rat hepatocytes was investigated. It was found that thiourea toxicity, as evidenced by an increase in LDH-leakage from the cells, was accompanied by a depletion of intracellular glutathione (GSH). No increase in lipid peroxidation was observed with any of the thiourea. Burimamide and thioperamide, thiourea-containing histamine receptor ligands, were also found to deplete intracellular GSH. A clear structure-toxicity relationship was uncovered among a homologous series of N-phenylalkylthiourea. N-benzylthiourea (BTU) and N-phenylethylthiourea (PETU) were found to be non-toxic at a concentration of 1 mM, while N-phenylpropylthiourea (PPTU) and N-phenylbutylthiourea (PBTU) were found to cause significant LDH-leakage from the cells, accompanied by a depletion of intracellular GSH. This structure-toxicity relationship was further investigated using hepatocytes of differentially induced rats, however, no significantly different results were obtained when using hepatocytes of rats induced with phenobarbital (PB) or beta-naphthoflavone (BNF). Oxidation of the thiourea moiety is thought to be the first step in the bioactivation of thiourea containing compounds. The oxidation of thiocholine sulfenic acids, produced by FMO-mediated oxidation of the thiourea moiety, was used to determine whether the compounds examined are substrates for the FMO enzymes in rat liver. No clear relationship was found between cytotoxicity of the mono-substituted thiourea and lipophilicity of the N-substituent, nor with the FMO-mediated oxidation of the thionosulfur atom of the mono-substituted thiourea. It is concluded from this study, that thiourea toxicity in rat hepatocytes is structure-dependent and manifests itself as LDH-leakage and as a depletion of intracellular non-protein sulfhydryls, notably GSH, most likely followed by alkylation of vital macromolecular structures.