O’Brien, Peter C.

Abstract To describe the demographic and tumor related characteristics and outcomes for patients with primary T-cell central nervous system lymphoma (TPCNSL). A retrospective series of patients with TPCNSL was compiled from twelve cancer centers and seven countries. This study involved 35 male and 10 female patients with a median age of 60 years (range 3–84). Twenty (44%) had Eastern Cooperative Oncology Group performance status (PS) of 0 or 1. Twenty six (58%) had involvement of a cerebral hemisphere and sixteen (36%) had lesions of deeper sites in the brain. Two patients had primary spinal cord lesions and one had meningeal disease only. Serum lactate dehydrogenase (LDH) was elevated in 7 of the 22 cases (32%) and cerebrospinal fluid (CSF) protein was elevated above normal in 19 of the 24 cases (79%) with available data. The median disease specific survival (DSS) for all patients was 25 months (95% confidence interval (CI) 11–38 months). The two and five-year DSS were 51 % (CI 35–66 %) and 17 % (CI 6–34 %) respectively. Univariate and multivariate analyses were conducted for the following factors: age (≤ 60 vs. > 60 years), PS (0 or 1 vs. 2, 3 or 4), involvement of deep structures of the central nervous system (no vs. yes), and methotrexate (MTX) use in the primary treatment (yes vs. no). Only PS and MTX use were significantly associated with better outcome with hazard ratios (HR) of 0.2 (CI 0.1–0.4) and 0.4 (CI 0.2–0.8) respectively. This is the largest series ever assembled of TPCNSL. The presentation and outcome appear similar to that of PCNSL of B cell origin. PS 0 or 1 and administration of MTX are associated with better survival. TPCNSL does not appear to require a different therapeutic management approach than B-cell PCNSL.

Abstract Of eight methods examined for measuring plasma hemoglobin in micromolar concentration, all exhibited acceptable linearity, reproducibility, and concurrence except when specimens were icteric or lipemic or contained methemoglobin or methemalbumin. Measurement of absorbance at 578 nm with an Allen correction permits precise assay of plasma oxyhemoglobin concentration as low as 0.01 g/L (1 mg/dL, 0.16 mumol/L), unaffected by hyperlipidemia or hyperbilirubinemia. Discrepancies between methods occurred in 11.6% of a consecutive series of 50 nonicteric patients' plasma specimens. Examination of absorption spectra is helpful when discrepancies are observed between methods. The presence of methemalbumin or methemoglobin in plasma is not recognized by methods that measure only oxyhemoglobin. Increased ceruloplasmin or beta-carotene does not significantly affect results.

An estimate of total body muscle mass with dual-energy X-ray absorptiometry (DXA; appendicular muscle mass divided by 0.75) was compared with 24-h urinary creatinine excretion in 59 healthy men and women [20–30 yr (younger), 45–59 yr (middle age), and 60–79 yr (older)] who stayed in a clinical research center for 5 days. Total body water (2H2O dilution), fat (underwater weighing), bone mineral (DXA), and total body protein mass (based on a 4-compartment model) were also measured. Muscle mass estimates by DXA and creatinine were highly correlated ( r = 0.80). However, stepwise multiple regression indicated that a significant amount of additional between-subject variability in DXA-based muscle mass estimates could be explained by total body water. Creatinine excretion, knee extensor strength, and total body protein mass all decreased with age, suggesting a decline in muscle cell mass with aging. However, DXA-based muscle mass and measures of nonfat body mass (i.e., lean body mass by2H2O and fat-free body mass by underwater weighing) did not change with age. These results indicate that DXA and urinary creatinine excretion give different results regarding the decline in total body muscle mass with aging. The factor(s) responsible for the apparent underestimate of age-related sarcopenia by DXA remain to be fully defined, but changes in body water may be an important contributor.

Measurement of glucose turnover under non-steady-state conditions has proven problematic. When the mass of the glucose pool is not changing (i.e., glucose concentrations are constant) non-steady-state error can be minimized if all glucose entering the circulation has the same specific activity as plasma [radioactive infused glucose (hot-GINF) method]. Alternatively, a second tracer can be used to measure the effective volume of glucose [variable-pV method of Issekutz (T. Issekutz, R. Issekutz, and D. Elahi. (Can. J. Physiol. 52:215-224, 1974)]. To determine whether these techniques provide concordant assessments of insulin action under non-steady-state conditions, glucose turnover was measured in six subjects. After initiation of insulin (0.6 mU.kg-1 x min-1), both methods indicated similar rates of suppression of hepatic glucose release, which was complete by approximately 100-120 min. In contrast, the traditional fixed-pV method of Steele (R. Steele, J. Wall, R. DeBodo, and N. Altszuler. Am. J. Physiol. 187:15-24 1956) underestimated turnover (P < 0.01) resulting in apparent complete suppression of glucose release within approximately 40 min (P < 0.01 vs. other methods). The hot-GINF and variable-pV methods also yielded similar estimates of turnover after discontinuation of insulin. Both indicated that resumption of hepatic glucose release was slower (P < 0.01) and fall of glucose uptake faster (P < 0.01) than suggested by the fixed-pV method. Thus both the hot-GINF and variable-pV methods avoid non-steady-state error introduced by the fixed-pV method and provide concordant assessments of the rate of onset and offset of insulin action.

The quality of the epidemiological data on diabetic neuropathies remains poor for a variety of reasons. They include variability in 1) ascertainment of diabetes, 2 the clinical varieties of diabetic patients studied, 3) characterization of neurological dysfunction, 4) abnormal limits for neurological examinations and tests, 5) minimal criteria for neuropathy, 6) correct attribution of nondiabetic neurological disease, 7) correct attribution of type of neuropathy, 8) estimating neuropathy from use of multiple tests, and 9) estimating severity of polyneuropathy. We have tried to remedy these shortcomings in the Rochester Diabetic Neuropathy Study (RDNS). It was not possible to adequately characterize and quantitate diabetic polyneuropathies using only one or two clinical or test abnormalities. To estimate severity of diabetic polyneuropathy, the results of the neurological examination and abnormalities of nerve conduction, quantitative sensory tests, and quantitative autonomie tests were combined into a composite score. One begins by scoring a standard test of neurological deficits (impairments) of the lower limbs (NIS[LL]) and adds to this transformed numbers for percentile abnormality of seven good functional tests. This NIS(LL)+7 tests score appears to provide a much more comprehensive and stable numeric score by which to diagnose and grade severity of diabetic polyneuropathy than does the use of individual clinical or test results. This test score should be useful as a measure of change in diabetic polyneuropathy for purposes of medical practice, epidemiology studies, and controlled clinical trials. The staging approach that we introduced previously continues to provide an important measure of overall severity of diabetic polyneuropathy, taking into account both symptoms and impairments.