Budget Allocation for Steel Bridge Paint Maintenance

Government authorities are responsible for managing their available budget so that they gain maximum benefit. Therefore, they must make intelligent decisions as to which projects will be funded and the degree of funding. Dynamic programming (DP), integer programming (IP), and greedy heuristic (GH) approaches have been applied to optimize a two-year budget allocation for repainting steel bridges in Indiana. The optimal solution and the objective function values resulting from application of DP, IP, and GH are similar. The Indiana Department of Transportation (INDOT) divides Indiana into six districts. The results show that District 1 has the highest budget allocation percentage (28%). It has the lowest percent in the first year and the highest percent in the second year. District 2 has the lowest percentage (11%). A sensitivity analysis has been completed to show the potential alternative solutions that assist INDOT decision makers in solving their budget allocation problems.     

Stability of cefodizime in solution and compatibility with other injectable drugs

The stability of cefodizime in five intravenous infusion fluids (0.9% sodium chloride, 5% dextrose in water, 10% dextrose in water, 5% amino acid injection, 3% polygeline) was studied at room temperature and at 4 degrees C. The compatibility of cefodizime with commonly used injectable drugs (ranitidine, metoclopramide, folinic acid, furosemide, aminophilline, methylprednisolone, betamethasone, hydrocortisone, dexamethasone, ketoprofen, noramidopyrine, acetylcysteine, digoxin, diazepam, acetylsalicylic acid, chlorpromazine, clonidine, clomipramine) was studied in 0.9% sodium chloride and 5% dextrose at room temperature. At intervals during the storage periods (up to 24 hrs at room temperature; up to 6 days at 4 degrees C) color, clarity and solution pH were examined; cefodizime content was determined by a microbiological method. Cefodizime concentrations remained greater than 90% of the initial concentrations in all infusion fluids for at least 24 hrs at room temperature and 6 days at 4 degrees C. No visual changes or appreciable changes in pH were observed for any of the solutions. Immediate clouding was observed when chlorpromazine was combined with the solution of cefodizime. A color change was observed when acetylcysteine was mixed with cefodizime. An increase in pH was noted when aminophilline was added to the solution of cefodizime. However, cefodizime concentrations remained greater than 90% of the initial concentrations of the solutions after mixture with all the tested drugs for at least 24 hrs at room temperature.(ABSTRACT TRUNCATED AT 250 WORDS)     

Action of prostanoids on the emetic reflex of Suncus murinus (the house musk shrew)

Several prostanoids were investigated for a potential to induce emesis in Suncus murinus. The TP receptor agonist 11alpha,9alpha-epoxymethano-15S-hydroxyprosta-5Z,13E-dienoic acid (U46619) induced emesis at doses as low as 3 microg/kg, i.p. but the DP receptor agonist 5-(6-Carboxyhexyl)-1-(3-cyclohexyl-3-hydroxypropyl) hydantoin (BW245C) was approximately 1000 times less potent. The emetic action of U46619 (300 microg/kg, i.p.) was antagonized significantly by the TP receptor antagonist, vapiprost (P<0.05). EP (prostaglandin E(2), 17-phenyl-omega-trinor prostaglandin E(2), misoprostol and sulprostone), FP (prostaglandin F(2alpha) and fluprostenol) and IP (iloprost and cicaprost) receptor agonists failed to induce consistent emesis at doses up to 300-1000 microg/kg, i.p. Fluprostenol reduced nicotine (5 mg/kg, s.c.)-but not copper sulphate (120 mg/kg, intragastric)-induced emesis; the other inconsistently emetic prostanoids were inactive to modify drug-induced emesis. The results indicate an involvement of TP and possibly DP and FP receptors in the emetic reflex of S. murinus.     

用Na2S03与NH3分银实验研究

介绍了阳极泥处理过程中,氯化分金渣用Na2S03分银与NH3分银的工艺过程;研究了Na2S03分银Na2S03用量、pH、时间对分银效果的影响,以及甲醛还原温度、pH对银还原率的影响,以及NH3分银NH,浓度、时间对分银效果的影响,并对水合肼还原时水合肼用量、时间、温度对银还原率进行了研究．结果表明,用Na2S03分银-甲醛还原,当Na2S03的用量为理论量1．3倍,pH值为9．2,浸出时间4h时,银浸出率可达97.39％,当甲醛用量为（甲醛：银=1：2．5）,pH值为10．5,反应4h,温度为30-40℃时,银还原率可达96．33％;用NH,分银-水合肼还原,当NH3浓度为8％-10％,温度为室温,反应时间为4h时,银浸出率可达96．23％,当水合肼用量为理论量2倍,温度60℃,还原0．5h时,银还原率可达98．1％．     

用Na2SO3与NH3分银实验研究

介绍了阳极泥处理过程中, 氯化分金渣用Na₂SO₃分银与NH₃分银的工艺过程; 研究了Na₂SO₃分银Na₂SO₃用量、pH、时间对分银效果的影响, 以及甲醛还原温度、pH对银还原率的影响, 以及NH₃分银NH₃浓度、时间对分银效果的影响, 并对水合肼还原水合肼用量、时间、温度对银还原率进行了研究.结果表明, 用Na₂SO₃分银-甲醛还原, 当Na₂SO₃的用量为理论量1.3倍, pH值为9.2, 浸出时间4h时, 银浸出率可达97.39 %, 当甲醛用量为(甲醛:银=1:2.5), pH值为10.5, 反应4 h, 温度为30~40 ℃时, 银还原率可达96.33 %; 用NH3分银-水合肼还原, 当NH₃浓度为8 %~10 %, 温度为室温, 反应时间为4 h时, 银浸出率可达96.23 %, 当水合肼用量为理论量2倍, 温度60 ℃, 还原0.5 h时, 银还原率可达98.1 %.      

Poling forces during roller skiing: effects of technique and speed

PURPOSE: A substantial proportion of the propulsive forces required for uphill skiing are generated from the upper body, but no study has systematically examined poling forces at different slopes. In the present experiment, poling forces and timing were examined during roller skiing on 2.1% and 5.1% uphills. METHODS: Nine highly skilled cross-country skiers roller skied at paced submaximal and at maximal speeds using the V1 skate (V1) and double pole (DP) techniques. Poling forces and timing were measured with piezoelectric transducers. RESULTS: Peak force (PF), average force (AF) and average force over the entire cycle (ACF) were significantly greater (P < 0.01) at the steeper grade with both techniques. Values for the ratio of V1 to DP did not differ between the two grades for PF, AF, and ACF but tended to increase with velocity for both techniques. With both V1 and DP, upper body recovery time was shorter (P < 0.01) at the steeper grade, and cycle rate was greater (P < 0.01) at the steeper grade. CONCLUSIONS: We conclude that 1) the relative demands on the upper body with V1 compared with DP were similar between the two grades, and 2) the responses to an elevation in grade of increased poling forces, shortened poling recovery times, and increased cycle rate are comparable to the responses to an increase in speed.     

Sex determination and polyploid gigantism in the dwarf surfclam (Mulinia lateralis Say)

Mulinia lateralis, the dwarf surfclam, is a suitable model for bivalve genetics because it is hardy and has a short generation time. In this study, gynogenetic and triploid M. lateralis were successfully induced. For gynogenesis, eggs were fertilized with sperm irradiated with ultraviolet light and subsequently treated with cytochalasin B to block the release of the second polar body (PB2). Triploidy was induced by blocking PB2 in normally fertilized eggs. The survival of gynogenetic diploids was very low, only 0.7% to 8 days post-fertilization (PF), compared with 15.2% in the triploid groups and 27.5% in the normal diploid control. Larvae in all groups metamorphosed at 8-10 days PF, and there was no significant post-larval mortality. At sexual maturation (2-3 months PF), all gynogenetic diploids were female, and there was no significant difference (P > 0.05) in sex ratio between diploids and triploids. These results suggested that the dwarf surfclam may have an XX-female, XY-male sex determination with Y-domination. Compared with diploids, triploids had a relative fecundity of 59% for females and 80% for males. Eggs produced by triploid females were 53% larger (P < 0.001) in volume than those from diploid females. In both length and weight measurements at three months PF, the gynogenetic diploids were not significantly (P > 0.33) different from normal diploid females, suggesting that inbreeding depression was minimal in meiosis II gynogens. Triploid clams were significantly larger (P < 0.001) than normal diploids. We hypothesize that the increased body-size in triploids was caused by a polyploid gigantism due to the increased cell volume and a lack of cell-number compensation.     

Biomimicry, dental implants and clinical trials

The overall objective of this study was to develop pluronic F127 (PF127)-containing formulations of pilocarpine hydrochloride (PHCL) suitable for controlled-release ocular delivery of PHCL. Various aqueous formulations were evaluated containing 1% w/v PHCL and 25% w/v PF127 alone or with one of the following additives present: poly(ethylene glycol) 4600 (PEG), poly(vinylpyrrolidone) 10,000 (PVP), poly(vinyl alcohol) 10,000 (PVA), methylcellulose 15 cP (MC), and hydroxypropyl methylcellulose 80-120 cP (HPMC). The in vitro dissolution of the PF127 formulations and the pilocarpine release profiles from them were obtained simultaneously at 34 degrees C and room temperature using a membraneless in vitro model. It was observed that the PEG- and PVP-containing PF127 formulations of PHCL dissolved the quickest and released the drug at a significantly faster rate than the control PF127 formulation, which had no additive present. The PF127 formulations of PHCL containing MC or HPMC exhibited the slowest dissolution rates and released the drug the slowest. The same rank order was observed at each temperature for the dissolution and PHCL release profiles of each formulation. On the basis of the in vitro results, the PF127 formulations of PHCL containing MC or HPMC as an additive showed potential for use as controlled-release ocular delivery systems for PHCL.     

Mechanism of the paradoxical, inhibitory effect of phenobarbital on hepatocarcinogenesis initiated in infant B6C3F1 mice with diethylnitrosamine

Phenobarbital (PB), a classical rodent hepatopromoter, remarkably enhances hepatocarcinogenesis initiated by diethylnitrosamine (DEN) in adult B6C3F1 mice. However, it is also known to strongly inhibit liver tumor development in the B6C3F1 mice initiated with DEN in their infancy. The present study aimed to elucidate the unknown biological mechanisms for this paradoxical, inhibitory effect of PB on B6C3F1 mouse hepatocarcinogenesis. Male 12-day-old infant B6C3F1 mice were injected i.p. with DEN and, at 6 weeks of age, divided into PB-treated (PB+ group) and untreated (PB- group) animals. At 24 weeks, PB treatment was ceased for half of the PB+ animals (PB+/- group) and started for half of the PB- animals (PB-/+ group). Finally, all mice were sacrificed at 36 weeks and examined for the development of liver tumors. The mean multiplicity of gross tumors in the PB+ group was only one-fifteenth of that for the PB- group. PB-/+ animals developed fewer than half of the tumors found in PB- mice, indicating that the PB effect depends solely on the treatment duration, rather than the animal age. The effect was proven to be reversible, because the mean tumor multiplicity for the PB+/- group was seven times larger than that for the PB+ group. Stereological analysis revealed the mean volume of hepatocellular proliferative lesions in the PB- animals to be 7.7- and 4.1-fold the values for the PB+ and PB-/+ groups, respectively. The mean proliferating cell nuclear antigen-labeling indices for hepatocellular adenomas in PB+ and PB-/+ animals were also one-third of that for tumors in PB- animals, whereas no significant differences were observed with regard to the mean apoptotic index. In conclusion, the inhibitory effect of PB seemed to be primarily caused by the suppression of tumor cell proliferation. Irrespective of the group, most lesions observed were basophilic hepatocellular adenomas or foci, positive for Bcl-2 oncoprotein. They were thus distinct from the eosinophilic Bcl-2- lesions that predominate with PB promotion after the initiation of adult B6C3F1 mice. This age-dependent nature of initiation, together with the differential responses of Bcl-2+ and Bcl-2- lesions, may be responsible for the apparently contradictory outcomes of PB treatment in infant and adult B6C3F1 mice.     

Evaluating nicotine replacement therapy and stage-based therapies in a population-based effectiveness trial.

Pharmacological interventions for smoking cessation are typically evaluated using volunteer samples (efficacy trials) but should also be evaluated in population-based trials (effectiveness trials). Nicotine replacement therapy (NRT) alone and in combination with behavioral interventions was evaluated on a population of smokers from a New England Veterans Affairs Medical Center. Telephone interviews were completed with 3,239 smokers, and 2,054 agreed to participate (64%). Participants were randomly assigned to one of four conditions: stage-matched manuals (MAN); NRT plus manuals (NRT = MAN); expert system plus NRT and manuals (EXP = NRT = MAN); and automated counseling plus NRT, manuals, and expert system (TEL = EXP = NRT = MAN). Assessments were completed at baseline, 10, 20, and 30 months. The point prevalence cessation rates at final follow-up (30 months) were MAN, 20.3%; NRT = MAN, 19.3%; EXP = NRT = MAN, 17.6%; and TEL = EXP = NRT = MAN, 19.9%. Stage-matched manuals provided cessation rates comparable with previous studies. The addition of NRT, expert system interventions, and automated telephone counseling failed to produce a further increase in intervention effectiveness. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

In vitro oxidative decarboxylation of L-2-hydroxy-4-methylthiobutanoic acid by L-2-hydroxy acid oxidase A from chicken liver

The aim of this study was to assess prospectively acid-base changes after severe birth acidaemia. Fourty-five term babies with severe acidaemia (median umbilical artery pH 6.99 [Range 6.74-7.05], mean base deficit 16.3 [SD 3.7] mmol/l) were prospectively identified. Pathological cardiotocographs were present in 32 (71%) prior to delivery and 39 (87%) were delivered operatively; 27 for fetal distress. Sixteen required intubation. At one hour of age, median pH was 7.29 [Range 7.04-7.45] and the change in pH correlated with one hour pCO2 (r = 0.62 p < 0.001). pH measurements were obtained in 11 of the 16 babies with a 1 hour pH < or = 7.25 and all values had recovered by this time. Five of this group were receiving oxygen. Of the 11 babies admitted to NICU, 1 died and 3 had evidence of encephalopathy, all of which were normal at follow-up [2-12 months]. Recovery of pH after severe birth acidaemia was evident at 1 hour of age and would appear to be complete by 4 hours.     

Factors associated with limb loss despite a patent infrainguinal bypass graft

Lower-extremity limb salvage should parallel infrainguinal bypass graft patency. To determine factors associated with limb loss despite a patent bypass, we reviewed 191 consecutive infrainguinal bypasses in 158 patients followed prospectively over 42 months. In this series of 176 (92%) vein grafts, 15 (8%) expanded polytetrafluoroethylene grafts, 122 (64%) tibial artery bypasses, and 170 (89%) bypasses placed for limb salvage, 29 major lower-extremity (above-knee or below-knee) amputations were performed in 29 patients, 12 because of ischemia after graft thrombosis and 17 (9% of series) due to progression of soft tissue infection/necrosis despite a functioning bypass. Primary and secondary 36-month vein graft patencies by life-table analysis were 61 per cent and 81 per cent, respectively. When the 17 cases of limb loss were compared to the rest of the series, nonstatistically significant variables included male sex [11 (65%) vs 79 (56%); P = 0.608] and diabetes [12 (71%) vs 80 (57%); P = 0.310]. Statistically significant variables included black race [9 (53%) vs 39 (28%); P = 0.048]; chronic renal failure [6 (35%) vs 12 (9%); P = 0.005], placement to a tibial/pedal artery [15 (88%) vs 107 (62%); P = 0.034], distal anastomosis to the anterior tibial/dorsalis pedis (AT/DP) artery [8 (47%) vs 27 (16%); P = 0.004], and grafts requiring late revision [7 (41%) vs 22 (13%); P = 0.006]. Thirteen (76%) extremities had an intact pedal arch. Nine amputations were performed within 30 days (early group), and eight were performed from 45 days to 20 months (median, 8 months) after bypass placement (late group). The most common primary causes of limb loss in the early group were overwhelming progression of soft-tissue infection despite patent bypass (n = 4; 44%) and insufficient runoff in the foot (n = 3; 33%). In the late group, amputation most often followed long treatment of a chronic proximal diabetic neuropathic foot ulcer with osteomyelitis. Five (63%) grafts in this group were anastomosed to the AT/DP arteries. These data suggest that patients with chronic renal failure, chronic neuropathic heel ulcers, and an AT/DP bypass are at greater risk for amputation despite a working bypass, especially if the graft develops a hemodynamically significant stenosis. Careful judgment and patient selection under these circumstances are thus justified.     

Pharmacologic actions of subtype-selective and novel GABAergic ligands in rat lines with differential sensitivity to ethanol

Alcohol-nontolerant (ANT) rats, produced by selective breeding for high sensitivity to motor-impairing effects of ethanol, have a point mutation in the cerebellar gamma-aminobutyric acid type A (GABAA) receptor alpha 6 subunit, which has been proposed to underlie enhanced sensitivity to benzodiazepine agonists as well. We compared ANT and alcohol-tolerant (AT) rats using behavioral and neurochemical methods to assess the significance of alpha 6- and non alpha 6-containing GABAA receptor subtypes. Motor performance in a tilting plane test was largely unaffected by a type I benzodiazepine receptor-preferring agonist, zolpidem [1-10 mg/kg, intraperitoneally (IP)], partial benzodiazepine agonists bretazenil and ZG-63 (both at 40 mg/kg, IP), and a novel broad-spectrum anticonvulsant loreclezole (40 mg/kg, IP) in both ANT and AT rats. In contrast, diazepam (10 mg/kg, IP) impaired performance of the ANT but not AT animals. These data, supported by results from brain regional autoradiography of [3H]Ro15-4513 and membrane binding of [3H]ZG-63 and [35S]TBPS as influenced by these ligands, strongly suggest that only ligands with full agonist actions on mutant (ANT) but not wild-type (AT) alpha 6-containing GABAA receptors are able to produce motor impairment in the ANT rats.     

14C-Propoxyphene demethylation in the rat. An example of differences between liver and intestinal drug-presystemic metabolism

Presystemic metabolism is believed to occur mainly in the liver with some minor intestinal participation. The aim of this study was to investigate the respective part of each of these two organs in the metabolism of the analgesic d-propoxyphene (DP). Pharmacological doses of DP were given in the duodenum (ID), the portal vein (IP), and the femoral vein (IV) of male Wistar rats. A tracer dose of 14C-DP was also administered either in IV, IP, or ID as well as in hepatectomized rats or rats with bile duct diversion. In vitro demethylation occurring in liver and intestinal microsomes was also studied. Absolute DP bioavailability obtained after oral administration was two times higher than that observed after portal administration (48.9% vs. 23.2%, respectively), an result opposite (i.e. a lower bioavailability) of that expected on the basis of the existence of a liver enzyme saturation phenomenon. The 14CO2 cumulative excretion after 14C-DP administration was significantly lower after IV or ID administration than after injection in the portal vein as a bolus or within 20 min. The biliary excretion of the labeled compound varied in the opposite direction, being greater after IV or ID than after IP administration, suggesting that the metabolism of DP in the liver is influenced by an extrahepatic transformation. This most likely occurs in the gut since the production of 14CO2 after IV administration was similar to that after ID administration. This transformation did not prohibit DP detection in the systemic blood but was sufficient to increase the part eliminated with bile and to decrease the part demethylated into NP. Demethylation mainly occurs in the liver since the production of 14CO2 was nearly abolished in hepatectomized rats. Furthermore, microsomes of hepatic but not of intestinal origin were able to demethylate DP. Our data suggest that the transformation of DP occurring in gut after oral administration is responsible for changes in the hepatic metabolism of the drug.     

Meta-Analysis of the Efficacy of Nicotine Replacement Therapy for Smoking Cessation: Differences Between Men and Women.

Gender differences in the efficacy of nicotine replacement therapies (NRTs) were examined in a meta-analytical review of 90 effect sizes obtained from a sample of 21 double-blind, placebo-controlled randomized studies. Although NRT was more effective for men than placebo at 3-month, 6-month, and 12-month follow-ups, the benefits of NRT for women were clearly evident only at the 3- and 6-month follow-ups. Giving NRT in conjunction with high-intensity nonpharmacological support was more important for women than men. That is, NRT and low support were efficacious for women at only short-term follow-up, and men benefited from NRT at all the follow-ups regardless of the intensity of the adjunct support. The results suggest that long-term maintenance of NRT treatment gains decrease more rapidly for women than men. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Short- and long-term smoking cessation for three levels of intensity of behavioral treatment.

Efficacy and costs of 3 levels of medical–behavioral treatment intensity in conjunction with nicotine replacement therapy (NRT) were compared in 240 one-pack-a-day smokers: (a) a low-intensity (LI) group that received 8 weeks of NRT (n?=?80) and 1 advice and education (A&E) session with a nurse practitioner (NP); (b) a moderate-intensity (MI) group that was provided NRT and 4 A&E sessions with an NP (n?=?80), and (c) a high-intensity (HI) group that received treatment combining NRT, 4 A&E sessions, and 12 weeks of individualized cognitive–behavioral therapy (n?=?80). Biochemically confirmed abstinence rates at 9, 26, and 52 weeks posttreatment initiation were highest for the HI (45%, 37%, 35%) group, followed by the LI (35%, 30%, and 27%) and MI (27%, 12%, 12%) groups. Group differences approached statistical significance at 9 weeks and were statistically significant at both 26 and 52 weeks. The cost of LI treatment was $308, that of MI was $338, and the HI treatment cost was $582. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Regulation of E2F4 mitogenic activity during terminal differentiation by its heterodimerization partners for nuclear translocation

E2F/DP heterodimers play a pivotal role in the regulation of cell growth and differentiation. A decrease in E2F/DP activity occurs during cell cycle arrest and differentiation. However, very little is known about the specific role of the various E2F/DP members along the transition from proliferation to terminal differentiation. We have previously shown that E2F4 accounts for the vast majority of the endogenous E2F in differentiating muscle cells. Here, we show that E2F4, which lacks a nuclear localization signal (nls), is distributed in both the nucleus and the cytoplasm, in either asynchronously growing myoblasts or differentiated myotubes. E2F4 nuclear accumulation is induced by the binding in the cytoplasm with specific partners p107, pRb2/p130, and DP3delta, an nls-containing spliced form of DP3, which provide the nls. Although overexpression of E2F4/DP3delta reactivates the cell cycle in quiescent cells, the E2F4 nuclear accumulation induced by pRb2/p130 and p107 correlates with cell growth arrest Moreover, E2F4/DP3delta-induced cell cycle reactivation is efficiently counteracted by either p107 or pRb2/p130 overexpression. Reinduction in quiescent cells of DNA synthesis by E2F1/DP1 overexpression is abrogated by coexpression of pRb and is hampered by MyoD overexpression. Both pRb2/p130 and pRb, as well as MyoD, are up-regulated in myotubes. Accordingly, multinucleated myotubes, which are induced to reenter the S-phase by oncoviral proteins, are refractory to cell cycle reactivation by forced expression of E2F4/DP3delta or E2F1/DP1. Thus, E2F/DP repression represents only one of multiple redundant circuits that control the postmitotic state in terminally differentiated cells and that are targeted by adenovirus E1A and SV40 large T antigen.     

Recognition of novel artifacts produced during the microsomal incubation of secondary alicyclic amines in the presence of cyanide

1. During the in vitro microsomal metabolism of the secondary alicyclic amines, nornicotine, anabasine or 4-benzylpiperidine in the presence of cyanide, a new product was formed. 2. Comparison of these new products with authentic compounds by hplc and ms showed they were the corresponding 1'-N-cyanomethyl compounds. 3. The source of the methylene group was shown to be formaldehyde, arising during incubation, from either microsomal lipid and/or glycerol used to store microsomes for long periods at low temperature. 4. The formation of the 1'-N-cyanomethyl compounds was enhanced in the presence of substrates producing formaldehyde during their metabolism, in direct relationship to the amount of formaldehyde generated. 5. The results indicate that care should be taken in interpreting data obtained from incubates containing secondary amines and cyanide, especially in the presence of substrates capable of donating formaldehyde.     

The role of different pedigree structures on the sampling variance of heritability estimates

A computer-intensive process was performed to simulate 12,600 data sets each with n = 5,000 individuals from distinct pedigree structures to assess the effect of pedigree information on the sampling variance of heritability (h2) estimates. Pedigree structures were determined by varying the proportion of foundation animals (PF), percentage replacement rates for males (RM) and females (RF), and ratio of females to male (F2M). A 2(3) factorial design was modeled; levels of RM and RF were 10 and 20%, and levels of F2M were 10 and 20. For each of the eight cells, 60 foundation animals were simulated, each with 10 replicates. The required mating seasons (MS) to obtain the number of individuals was simulated based on PF and F2M. A REML algorithm was used to estimate h2 and its associated SE. The effect of all factors was analyzed in a regression model with linear and quadratic components for PF. An alternative model with MS replacing PF was also investigated. There was a non-monotonic association (P < .01) between PF and h2 SE. The minimum h2 SE occurred when PF ranged from 20 to 40%. Here, the proportion of first-generation progeny was near its maximum with rapid increases in the proportion of subsequent descendants. Among the class effects, F2M yielded the highest mean square (P < .001). When considering more than one MS, h2 SE was positively associated (P < .01) with RF and F2M and negatively associated with RM. Results suggest that h2 is most accurately estimated when there is performance information on many animals closely related to foundation animals.     

Polycythemia vera treated with pipobroman as single agent: low incidence of secondary leukemia in a cohort of patients observed during 20 years (1971-1991)

The 'gold standard' for the treatment of polycythemia vera (PV) is to date undefined. We performed a retrospective analysis to evaluate the outcome of a cohort of PV patients treated with pipobroman (PB) at a single institution during a period of 20 years (November 1971-October 1991). During this period, a total of 366 adult PV patients were diagnosed according to Polycythemia Vera Study Group (PVSG) criteria. Of these, only 199 (54%) were treated with PB: 92 were males and 107 females, median age was 63.0 years (range 25.2-87.3 years). Major clinical characteristics at onset were as follows: 34 (17%) patients had splenomegaly >3 cm below costal margin, 70 (35%) had platelets >600,000/mm3, 79 (40%) had white blood cells >12,000 mm3; 97 (49%) had hypertension, 83 (42%) had minor neurological symptoms (as vertigo, headache, paresthesias), 33 (17%) had pruritus and 27 (13%) had thrombotic features. All patients received PB at the dosage of 1 mg/kg/day until response was achieved (hematocrit value <50% in males and <45% in females). Thereafter treatment was given according to toxicity and maintenance of response. All patients were phlebotomized before starting treatment (mean number of phlebotomies performed: three, range 2-4) and 47 of them received PB when hematocrit value was already reduced at response levels: therefore, while all patients are evaluable for acute and long-term toxicity, only 152/199 (76.4%) patients are evaluable for response to PB. During a median time of 2 months, all these 152 patients achieved the response; as maintenance, 128/199 (64.3%) patients were managed with PB alone and 71/199 (35.7%) patients received phlebotomies occasionally. Sixty-one out of 199 (30.6%) patients developed disease-related complications (25 neurological symptoms, 21 thrombotic complications, 12 cardiovascular problems, three hepatic failures). Eleven (5.5%) patients developed acute myelogenous leukemia (AML) after a median time of treatment of 89 months (range 33-188 months), 11 (5.5%) patients developed myelofibrosis (median time from treatment 71 months, range 31-182 months) and in six (3%) patients cancer occurred (median time from treatment 85 months, range 13-118 months). The cumulative risk of leukemia in PV was 2% (95% CI: 0-4%) and 6% (95% CI: 1-11%) at 5 and 10 years respectively; the cumulative risk of myelofibrosis was 2% (95% CI: 1-5%) and 9% (95% CI: 3-15%) at 5 and 10 years, respectively. As of May 1996, 33 (16.6%) patients are lost to follow-up, 40 (20.1%) are dead and 126 (63.3%) are alive with a median overall survival of 191 months. In conclusion, this retrospective analysis confirms the efficacy and safety of PB in PV patients and its low leukemogenic role; prospective studies are needed to evaluate the real impact of PB in the treatment of PV.