Pathological variables determining the prognosis of non-Hodgkin''s lymphomas

The aim of the study was to assess the role of pathological grade, cell proliferation, ploidy, immunophenotype and site in determining the prognosis of non-Hodgkin's lymphomas. Of particular interest was the relative value of grades derived from the Kiel classification as opposed to the National Cancer Institute (NCI) working formulation. The study consisted of 181 cases, treated in a relatively uniform way over an 18-month period spanning 1986. Using life table analysis, both NCI working formulation grade and Kiel grade correlated strongly with survival. However, the differences between grades were entirely due to an excess of early deaths in the high-grade and intermediate-grade categories. In patients surviving greater than 0.1 years (37 days), phenotype, site, ploidy and cell proliferation had no effect on survival. There was no evidence that intermediate-grade tumours, when subdivided into Kiel low- and high-grade types, differed in survival from tumours graded as low- or high-grade by both methods. However, NCI working, formulation high-grade tumours, especially those with a high proliferation rate, formed a group with a very high likelihood of death within 0.1 years.     

Use of the Pericardial Fat Pad in Pulmonary Transplantation

Historically, the healing of tracheal or bronchial anastomoses has been the Achilles heel in pulmonary transplantation. In the past, steps taken to enhance healing of these structures and have allowed single-lung, double-lung, and heart-lung transplantation to be accomplished safely. This report presents a simplified technique for protection of the tracheal anastomosis in heart-lung and double-lung transplantation. This technique, wherein the pericardial fat pad from the right side is utilized to wrap the tracheal anastomosis, not only allows for excellent healing of the anastomosis but separates the aorta from the trachea. In 19 patients having heart-lung (N = 13) or double-lung (N = 6) transplantation there were no tracheal healing problems, dehiscence or stenosis found.     

Subgroups of smokers with different success rates after use of transdermal nicotine

To identify subgroups of smokers with different success rates, we applied "tree-structured survival analysis" (TSSA) to data from a previously published trial of transdermal nicotine. The subjects who received active treatment (14 mg patch, n 275, or the 21 mg patch, n 262) constituted the sample for this analysis. Using age, gender, the Fagerstrom Tolerance Questionnaire (FTQ), motivation to quit, number of cigarettes smoked at baseline, and body mass index (BMI) as classification variables, TSSA identified two subgroups within the 14 mg patch group and four subgroups of smokers within the 21 mg patch group. Among those receiving the 14 mg patch, individuals with a BMI greater than 26.4 kg/m relapsed sooner than did those with a BMI less than or equal to this value. Within the 21 mg patch group, the survival curve for males was significantly different from that observed in females, with males experiencing a longer time to relapse after treatment than did females. Among males, those who were less dependent relapsed significantly later than did those men who were more dependent. Among females, those with a higher motivation to quit relapsed more slowly than did those women with less motivation to quit. This information may be helpful to clinicians seeking to match specific patients to specific treatments with transdermal nicotine in order to maximize treatment outcomes.     

Developmental Neurotoxicity Evaluation of Orally Administered Isopropanol in Rats

Isopropanol was administered by gavage to timed-mated rats fromGestation Day (GD) 6 through Postnatal Day (PND) 21. Doses administeredwere 0, 200, 700, or 1200 mg/kg/day in a volume of 5 ml/kg.The dams were allowed to deliver and body weights and food consumptionwere recorded during gestation and lactation. Pups were counted,examined, sexed, and weighed on PND 0, 4, 7, 13, 17, 21, 36,49, and 68. Litters were culled to eight pups (4:4 or 5:3 sexratio) on PND 4 and litters without acceptable numbers of maleand female pups were eliminated from the study. Pups were weanedon PND 22, and two pups from each litter and their dams werekilled. Six of these pups from each dose group were perfusedin Situ for histopatho logical examination of the central andperipheral nervous sys tem. Brains of the remaining pups weredivided into four regions and weighed. Maternal liver and kidneyweights were re corded. Weaned pups were assessed for day oftestes descent or vaginal opening and for motor activity onPNDs 13, 17, 21, 47, and 58; auditory startle on PNDs 22 and60; and active avoidance on PNDs 60–64. These pups wereeuthanized and examined on PND 68. One high-dose dam died onPND 15, but there were no other clinical observations or effectson maternal weight, food consumption, or gestation length. Pupsurvival, weight, sex ratio, and sexual maturation were unaffected.There were no biologically significant findings in the behavioraltests, no changes in organ weights, and no pathological findingsthat could be attributed to isopropanol exposure. In conclusion,there was no evidence of developmental neurotoxicity associatedwith isopropanol exposure as high as 1200 mg/kg/day.     

Subchronic Oral Toxicity Study of Diisopropyl Methylphosphonate in Mink

Diisopropyl methylphosphonate (DIMP), produced during manufactureof the chemical agent GB (Sarin), is a groundwater contaminantat Rocky Mountain Arsenal, Colorado. DIMP was fed for 90 daysto dark brown "Ranch Wild" mink housed under controlled indoorconditions. One-year-old mink, 10 of each sex, were fed 0, 50,450, 2700, 5400, or 8000 ppm in standard ranch diet. ActualDIMP consumption was 0, 8, 73, 400, 827, and 1136 mg/kg bodywt/day, respectively. Two additional groups of 10 served as"pair-fed" controls. Body weight and food intake were recordedweekly. Complete blood count and 15 chemical analytes were measuredat Weeks 0, 3, 7, and 13. Necropsy and microscopic examinationwere performed on all mink. No clinical morbidity or deathsoccurred. Both sexes fed 8000 ppm ate approximately 20% lessand weighed approximately 20% less than the controls; 5400 ppmfemales had a 10% weight decrement. Plasma cholinesterase (ChE)decreased in the top three dose groups starting at Week 3. At13 weeks, decrements were approximately 50% but returned tonormal after 1 week without DIMP. Erythrocyte ChE was not reduced.Heinz bodies occurred in 10–15% of RBCs in 50% of 8000ppm mink at 13 weeks, and 0.1–2.0% of RBCs in 25% at 2700ppm. There were mild decreases in RBC count, hematocrit, andhemoglobin, and increases in reticulocyte count, at the 5400and 8000 ppm doses. All recovered within 3 weeks after DIMPwas with drawn. The 8000 ppm group had marginal splenic hematopoiesis,histologically. No other treatment-related changes were noted.The 450 ppm dose was a clear no-effect level (approximately73 mg DIMP/kg body wt/day). Compared to reports of similar studiesof DIMP in rats and dogs, these mink displayed no unique speciessusceptibility.     

Disposition and Pharmacokinetics of Isopropanol in F-344 Rats and B6C3F1 Mice

The absorption, metabolism, disposition, and excretion of isopropanol(IPA) were studied in male and female rats and mice. Animalswere exposed by iv (300 mg/kg) and inhalation (500 and 5000ppm for 6 hr) routes; additionally, IPA was given by gavageto rats only in single and multiple 300 and 3000 mg/ kg doses.In the rat approximately 81–89% of the administered dosewas exhaled (as acetone, CO₂, and unmetabolized IPA); approximately76% of the dose in mice was exhaled after iv bolus but 92% wasexhaled following inhalation. Approximately 3–8% of theadministered dose was excreted in urine as IPA, acetone, anda metabolite tentatively identified as isopropyl glucuronicacid. Small amounts of radiolabel were found in feces and inthe carcass. There were no major differences in the rates orroutes of excretion observed either between sexes or betweenroutes of administration. Additionally, repeated exposure hadno effect on excretion. However, both the route of administrationand the exposure or dose level influenced the form in whichmaterial was exhaled. Following exposure to 5000 ppm, a greaterpercentage of unmetabolized IPA was recovered in the expiredair than following exposure to 500 ppm, implying saturationof metabolism.     

Evidence for a light chain restriction of glycoprotein Ib/IX and Ilb/IIIa reactive antibodies in chronic idiopathic thrombocytopenic purpura (ITP)

To address the assumption of clonally restricted antibodies in immune thrombocytopenias we studied sera from 19 patients with chronic ITP known to possess antibodies reactive with glycoprotein (GP) Ib/IX and/or GPIIb/IIIa. These sera were re-analysed using the standard monoclonal antibody immobilization of platelet antigens (MAIPA) assay and 16 patients exhibited IgG antibodies reactive with GPIIb/IIIa; seven patients showed also a reactivity with GPIb/IX. Employing a light-chain-specific MAIPA assay, 75% (12/16) of these sera displayed GPHb/ Ilia-specific antibodies that were light chain restricted; only 13% (2/16) of the GPIIb/IHa reactive sera showed a mixed kappa and lambda phenotype. A light-chain-restricted phenotype was also seen for the GPIb/IX reactive antibodies. To further substantiate these findings, the MAIPA assay was modified in order to avoid interference from human anti-mouse antibodies. A high frequency of light-chain restricted platelet antibodies was also found using the modified MAIPA technique. These results support the hypothesis of a clonal B-cell expansion in immune thrombocytopenias, producing antibodies with a restricted idiotype repertoire and reacting with a limited number of epitopes.     

Obese rats with deficient leptin signaling exhibit heightened sensitivity to olfactory food cues

The Zucker rat is used as a model of genetic obesity, and while Zucker rats have been well studied for their reduced sensitivity to leptin signaling and subsequent weight gain, little work has examined their responses to environmental signals that are associated with “hedonic” feeding. This study evaluated the effects of a high‐fat food olfactory cue (bacon) in stimulating nose‐poke food‐seeking behavior on first exposure (novel) and after a period of access for consumption (familiar) in lean and obese Zucker rats at either 4 or 12 months of age, and under ad‐lib fed (unrestricted; U) or chronically food‐restricted (70% of ad‐lib; R) conditions. Baseline nose‐poke levels were comparable amongst all groups. At 4 months of age, only ObU rats displayed increased behavioral activation to familiar food cues. Twelve‐month‐old Ob rats, regardless of diet, exhibited substantially greater food‐seeking behavior when exposed to both the novel and familiar olfactory cues. A strong positive correlation between body weight and nose‐poke entries for the familiar food cue was observed at both ages, while this correlation for the novel food cue was significant in 12–month‐old rats only. Similarly, there were strong positive correlations between food intake and poke entries for the familiar food cue was observed at both ages, while this correlation for the novel food cue was significant in 12–month‐old rats only. Although it is possible that differences in olfactory sensitivity contribute to these behavioral effects, our findings support the interactions between food intake, obesity, and food‐seeking behavior and are consistent with leptin inhibiting the brain's reactivity to food cues and suggest that the enhanced sensitivity to the food cues with leptin deficiency is likely to contribute to overeating and weight gain. Synapse, 2013. © 2012 Wiley Periodicals, Inc.