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The predictive value of white cell or CD34+ cell count in the peripheral blood for timing apheresis and maximizing yield.

BACKGROUND: The collection of peripheral blood stem and progenitor cells (PBPCs) for transplantation can be time-consuming and expensive. Thus, the utility of counting CD34+ cells and white cells (WBCs) in the peripheral blood was evaluated as a predictor of CD34+ cell yield in the apheresis component. STUDY DESIGN AND METHODS: The WBC and CD34+ cell counts in the peripheral blood and the apheresis components from 216 collections were assessed. Sixty-three patients underwent mobilization with chemotherapy plus filgrastim, and 17 patients and 14 allogeneic PBPC donors did so with filgrastim alone. The relationship between the number of WBC and CD34+ cells in the peripheral blood and in the apheresis component was analyzed by using rank correlation and linear regression analysis. RESULTS: The correlation coefficient for CD34+ cells per liter of peripheral blood with CD34+ cell yield (x 10(6)/kg) was 0.87 (n = 216 collections). This correlation existed for many patient and collection variables. However, patients with acute myeloid leukemia had fewer CD34+ cells in the apheresis component at any level of peripheral blood CD34+ cell count. Components collected from patients with CD34+ cell counts below 10 x 10(6) per L in the peripheral blood contained a median of 0.75 x 10(6) CD34+ cells per kg. When the WBC count in the blood was below 5.0 x 10(9) per L, the median number of CD34+ cells in the peripheral blood was 5.6 x 10(6) per L (range, 1.0-15.5 x 10(6)/L). A very poor correlation was found between the WBC count in the blood and the CD34+ cell yield (p = 0.12, n = 158 collections). CONCLUSION: The number of CD34+ cells, but not WBCs, in the peripheral blood can be used as a predictor for timing of apheresis and estimating PBPC yield. This is a robust relationship not affected by a variety of patient and collection factors except the diagnosis of acute myeloid leukemia. Patients who undergo mobilization with chemotherapy and filgrastim also should undergo monitoring of peripheral blood CD34+ cell counts, beginning when the WBC count in the blood exceeds 1.0 to 5.0 x 10(9) per L.

Adolescent↗

Direct HIV testing in blood donations: variation of the yield with detection threshold and pool size.

BACKGROUND: This study was designed to evaluate the potential yield of introducing nucleic acid amplification testing (NAT) in blood donation, according to the detection threshold and the pool size. STUDY DESIGN AND METHODS: A mathematical model of early HIV-1 population dynamics in blood has been developed and is used to predict the window period for NAT, according to the detection threshold and the pool size. The corresponding number of undetected, infected blood donations and the residual risk are estimated by using a previously published simulation model for the United States (9.96 million blood donations from regular donors, and an observed rate of HIV antibody-positive blood donations of 3.18/100,000) and for France (2.32 million blood donations, and a rate of antibody-positive donations of 0.9/100,000). RESULTS: The average window period from infection predicted by the mathematical model for NAT ranges from 8.4 to 15.6 days, according to the detection threshold and the pool size. The maximum yield of adding NAT to the current antibody tests is estimated at 14 donations for the United States and 2 for France. The maximum yield of adding NAT to the newly developed combined HIV antibody and p24 antigen tests is 7 donations for the United States and 1 for France. CONCLUSION: NAT at blood donation could reduce the HIV-1 window period to a minimal value of 8 days without pooling the blood samples, but the yield of NAT would be close to that of combined HIV antibody and p24 antigen tests for high values of the detection threshold and the pool size.

Blood Donors↗

A cell-kinetic model of CD34+ cell mobilization and harvest: development of a predictive algorithm for CD34+ cell yield in PBPC collections.

BACKGROUND: Mobilization and homing of PBPCs are still poorly understood. Thus, a sufficient algorithm for the prediction of PBPC yield in apheresis procedures does not yet exist. STUDY DESIGN AND METHODS: The decline of CD34+ cells in the peripheral blood during apheresis and their simultaneous increase in the collection bag were determined in a prospective study of 18 consecutive apheresis procedures. A cell-kinetic, four-compartment model describing these changes was developed. Retrospective data from 136 apheresis procedures served to further improve this model. A predictive algorithm for the yield was developed that considered the sex, weight, and height of the patient, the number of CD34+ cells in peripheral blood before apheresis, the inlet flow, and the duration of the apheresis. The accuracy of this algorithm was evaluated by comparison of the predicted and the observed yields of CD34+ cells in 105 prospective autologous and 148 retrospective allogeneic apheresis procedures. RESULTS: The correlation between predicted and observed yields was good for the autologous and allogeneic groups with a correlation coefficient (r) of 0.8979 and 0.8311 (p<0.0001), respectively. The regression is described by the equations log (measured value [m]) = 1.0118 + 0.8595 x log (predicted value [p]) for the autologous and log (m) = 2.226 + 0.7559 x log (p) for the allogeneic group. The respective equations for the zero-point regression are log (m) = 1.014 x log (p) and log (m) = 1.026 x log (p). The probability that the measured value was 90 percent or more of the predicted value was 83.8 percent for the autologous and 90.5 percent for the allogeneic apheresis procedures. CONCLUSION: The predictive accuracy of the algorithm and the slope of the zero-point regression curve were higher for allogeneic than autologous PBPC collections. The predictive algorithm may be a useful tool in PBPC harvest, enabling the adaptation of the size of the apheresis to the needs of each patient.

Algorithms↗

Effect of the G1896A precore mutation on drug sensitivity and replication yield of lamivudine-resistant HBV in vitro.

Hepatitis B e antigen (HBeAg) negative chronic hepatitis B (CHB) is frequently caused by a mutation (G1896A) in the hepatitis B virus (HBV) precore (PC) reading frame that creates a stop codon, causing premature termination of the PC protein. During lamivudine treatment, drug resistance develops at a similar rate in HBeAg positive and HBeAg negative CHB. Lamivudine-resistant HBV mutants have been shown to replicate inefficiently in vitro in the absence of PC mutations, but it is unknown whether the presence of PC mutations affects replication efficiency or antiviral sensitivity. This study utilized the recombinant HBV baculovirus system to address these issues. HBV baculoviruses encoding the G1896A PC stop codon mutation were generated in wild-type (WT) and lamivudine-resistant (rtM204I and rtL180M + rtM204V) backgrounds, resulting in a panel of 6 related recombinant baculoviruses. In vitro assays were performed to compare the sensitivities of the PC mutant viruses with lamivudine and adefovir and to compare relative replication yields. The PC mutation did not significantly affect sensitivities to either adefovir or lamivudine. WT HBV and PC mutant HBV showed similar replication yields, whereas the replication yields of the lamivudine-resistant mutants were greatly reduced in HBeAg positive HBVs, confirming previous observations. However, the presence of the PC mutation was found to compensate for the replication deficiency in each of the lamivudine-resistant mutants, increasing the replication yields of each virus. In conclusion, the PC stop codon mutation appears to increase the replication efficacy of lamivudine-resistant virus but does not affect in vitro drug sensitivity.

Adenine↗

Colonoscopy in elderly people is a safe procedure with a high diagnostic yield: a prospective comparative study of 2000 patients.

BACKGROUND AND STUDY AIMS: Optical colonoscopy is considered the gold standard for colorectal examination and has the advantage of allowing biopsies and polypectomy. However, the data on its safety and effectiveness in the elderly population are limited and somewhat conflicting. We prospectively assessed whether there are differences in completion rates, diagnostic yield, complication rates and 30-day mortality between patients aged > or = 65 years and patients aged < 65 undergoing colonoscopy at our centre. PATIENTS AND METHODS: Data were collected prospectively on 2000 colonoscopies performed over a 2-year period (January 2002 to January 2004). We compared 1000 consecutive colonoscopies in patients aged > or = 65 with 1000 consecutive colonoscopies in patients aged < 65 (control group). Data were collected on sedation; on completion rates, both crude and adjusted to discount failures due to obstructive disease; on diagnostic yield; complications, and on 30-day mortality. RESULTS: The median age was 75 years (51 % women) for the elderly group and 54 years (59 % women) for controls. The proportion of patients who received sedation was similar for both groups (59 % vs. 62 %, P = 0.97) but the mean dose of midazolam was lower in the elderly group (3.8 mg vs. 4.5 mg, P < 0.0001). The crude completion rate was lower for the elderly group (81.8 % vs. 86.5 %, P = 0.004), but the adjusted rate was similar for both groups (88.1 % elderly vs. 87.6 % control, P = 0.18). The overall diagnostic yield was higher in the elderly group (65 % vs. 45 %, P < 0.0001) with higher rates of carcinoma detected (7.1 % vs. 1.3 %, P < 0.0001). The complication rate was low (0.2 % per group). CONCLUSIONS: Colonoscopy in the elderly is safe and effective with a high diagnostic yield. Colonoscopy may now be the imaging modality of choice in the elderly population.

Adolescent↗

A quantum yield map for synthetic eumelanin.

The quantum yield of synthetic eumelanin is known to be extremely low and it has recently been reported to be dependent on excitation wavelength. In this paper, we present quantum yield as a function of excitation wavelength between 250 and 500 nm, showing it to be a factor of 4 higher at 250 nm than at 500 nm. In addition, we present a definitive map of the steady-state fluorescence as a function of excitation and emission wavelengths, and significantly, a three-dimensional map of the "specific quantum yield": the fraction of photons absorbed at each wavelength that are subsequently radiated at each emission wavelength. This map contains clear features, which we attribute to certain structural models, and shows that radiative emission and specific quantum yield are negligible at emission wavelengths outside the range of 585 and 385 nm (2.2 and 3.2 eV), regardless of excitation wavelength. This information is important in the context of understanding melanin biofunctionality, and the quantum molecular biophysics therein.

Biophysics↗

Nonlinear elasticity and yielding of depletion gels.

A microscopic activated barrier hopping theory of the viscoelasticity of colloidal glasses and gels has been generalized to treat the nonlinear rheological behavior of particle-polymer suspensions. The quiescent cage constraints and depletion bond strength are quantified using the polymer reference interaction site model theory of structure. External deformation (strain or stress) distorts the confining nonequilibrium free energy and reduces the barrier. The theory is specialized to study a limiting mechanical description of yielding and modulus softening in the absence of thermally induced barrier hopping. The yield stress and strain show a rich functional dependence on colloid volume fraction, polymer concentration, and polymer-colloid size asymmetry ratio. The yield stress collapses onto a master curve as a function of the polymer concentration scaled by its ideal mode-coupling gel boundary value, and sufficiently deep in the gel is of an effective power-law form with a universal exponent. A similar functional and scaling dependence of the yield stress on the volume fraction is found, but the apparent power-law exponent is nonuniversal and linearly correlated with the critical gel volume fraction. Stronger gels are generally, but not always, predicted to be more brittle in the strain mode of deformation. The theoretical calculations appear to be in accord with a broad range of observations.

Journal Article↗

Augmentation of lower esophageal sphincter pressure and gastric yield pressure after radiofrequency energy delivery to the gastroesophageal junction: a porcine model.

BACKGROUND: An endoscopic technique that eliminates gastroesophageal reflux disease would be of benefit to patients. The endoscopic delivery of radiofrequency energy to the porcine gastroesophageal junction was investigated and its effect on lower esophageal sphincter pressure, gastric yield pressure, and histology was assessed. METHODS: Twenty pigs underwent esophageal manometry and endoscopic injection of botulinum toxin (100 units) into the lower esophageal sphincter. After 1 week, animals were randomized to radiofrequency energy treatment of the gastroesophageal junction with a 4- needle catheter and thermocouple-controlled generator (n = 13) or no further intervention (control, n = 7). At 9 weeks, animals underwent esophagoscopy, manometry, gastric yield pressure determination, and sacrifice for histopathologic evaluation. RESULTS: Mean lower esophageal sphincter pressure declined by 3.7 +/- 2.6 mm Hg (control, p = 0.03) vs. 0.97 +/- 5.8 mm Hg (radiofrequency, p = 0.29) after 9 weeks. Mean gastric yield pressure was 24.9 +/- 8.2 mm Hg (control), compared with 43.4 +/- 10. 7 mm Hg (radiofrequency) (p = 0.0007). Histopathologic assessment demonstrated normal mucosa, mild fibrosis, and no inflammation. CONCLUSIONS: Radiofrequency energy delivery reversed much of the lower esophageal sphincter pressure reduction achieved with botulinum toxin injection and augmented gastric yield pressure by 75% compared with controls. Given the safety of radiofrequency energy delivery in this study and in other areas of medicine, human studies to assess the effect of radiofrequency energy on gastroesophageal reflux disease are warranted.

Animals↗

Yield of tissue sampling for submucosal lesions evaluated by EUS.

BACKGROUND: Evaluation of submucosal nodules or large gastric folds is a common indication for EUS. Establishing a tissue diagnosis is challenging because the yield of forceps biopsies is low. The aim of this study was to determine the diagnostic yield of EUS-guided endoscopic submucosal-mucosal resection and forceps biopsy for submucosal nodules and large gastric folds. METHODS: Patients who underwent EUS from March 1997 through January 2002 for evaluation of submucosal nodules or large gastric folds were identified, and the procedure and pathology reports reviewed. Patients were included who underwent endoscopic submucosal-mucosal resection (n = 45) or large-capacity ("jumbo") biopsy (n = 36) of submucosal lesions (arising from third endosonographic layer) or large gastric folds. Endoscopic submucosal-mucosal resection was performed with an electrosurgical snare or with a cap-fitted endoscopic mucosal resection device. RESULTS: Sixty-six patients (62% men; mean age, 61 years; range 27-80 years) underwent 69 EUS procedures to obtain tissue samples of subepithelial lesions. Diagnostic yields were as follows: endoscopic submucosal-mucosal resection 40/45 (89%; 95% CI [80%, 98%]), jumbo biopsy 15/36 (42%; 95% CI [26%, 58%]) (p < 0.001 by two-tailed Fisher exact test). There were 9 complications: 7 instances of bleeding (6 endoscopic submucosal-mucosal resection, 1 jumbo biopsy), 3 requiring hospitalization (2 endoscopic submucosal-mucosal resection, 1 jumbo biopsy) and 2 requiring transfusion; 1 chest pain and odynophagia (esophageal endoscopic submucosal-mucosal resection); and 1 oversedation (requiring administration of reversal agents). CONCLUSIONS: For submucosal lesions and large gastric folds, endoscopic submucosal-mucosal resection has a better diagnostic yield than the jumbo biopsy, but may have a higher complication rate.

Adult↗

Etiologic yield of subspecialists' evaluation of young children with global developmental delay.

OBJECTIVE: To determine the etiologic yield of subspecialists' evaluation of young children with global developmental delay. In addition, variables that may predict finding an underlying etiology were also identified. METHODS: All children <5 years of age, referred over an 18-month period to subspecialty services for initial evaluation of a suspected developmental delay, were prospectively enrolled. Diagnostic yield was ascertained after the completion of clinical assessments and laboratory investigations requested by the evaluating physician. RESULTS: Ninety-nine children (71 boys) were found to have global developmental delay; 96% had a mild or moderate delay documented. An etiologic diagnosis was determined in 44. Four diagnoses (cerebral dysgenesis, hypoxic-ischemic encephalopathy, toxin exposure, chromosomal abnormalities) accounted for 34 of 44 (77%) of the diagnoses made. The presence of co-existing autistic traits was associated with significantly decreased diagnostic yield (0/19 vs 44/80, P <.0001), whereas specific historical features (eg, family history, toxin exposure, and perinatal difficulty; 23/32 vs 21/67, P =.0002) and findings on physical examination (eg, dysmorphology, microcephaly, and focal motor findings; 35/48 vs 9/51, P <.0001) were significantly associated with identifying a diagnosis. Multiple logistic regression analysis identified antenatal toxin exposure, microcephaly, focal motor findings, and the absence of autistic traits as significant predictor variables for the identification of an etiology. CONCLUSION: An etiologic diagnosis is often possible in the young child with global developmental delay, particularly in the absence of autistic features. Etiologic yield is augmented by presence of specific findings on history or physical examination on initial assessment.

Autistic Disorder↗

Lupins and energy-yielding nutrients in ewes. II. Responses in ovulation rate in ewes to increased availability of glucose, acetate and amino acids.

An experiment, using a total of 320 Merino ewes, over two successive breeding seasons was conducted to investigate the separate effects of energy-yielding and protein-yielding nutrients on ovulation rate in sheep. The available energy-yielding or protein-yielding nutrients in the blood of sheep fed a maintenance pelleted ration were increased by either intravenous infusions of metabolites (acetate, glucose or acetate + glucose), feeding lupin grain, modification of the pattern of rumen fermentation to increase propionate production using the ionophore, lasalocid, or by feeding of ruminally undegradable protein (formaldehyde-treated casein). All treatments were given for 9 days prior to and including expected time of ovulation. Ovulation rates were measured by laparoscopy. In the first season (the 1984 experiment) when the effects of lupin grain, glucose + acetate and formaldehyde-treated casein were compared, ovulation rates were increased significantly in the group fed lupin (29%, P less than 0.001) and the group infused with glucose + acetate (24%, P less than 0.01). There was an apparent (17%) but statistically non-significant increase in the group fed casein. In comparisons between lupin grain, glucose, acetate, glucose + acetate, formaldehyde-treated casein and lasalocid in the 1985 experiment there were similar significant increases in ovulation rates in the groups fed lupin, and those infused with glucose or glucose + acetate (approximately 25%, P less than 0.001). The increase in the group infused with acetate was lower at 14% (P less than 0.05) and the increases of 7% in the groups fed casein or lasalocid were not significant.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetates↗

AKR murine leukemia virus genome: frequency of sequences in DNA of high-, low-, and non-virus-yielding mouse strains.

Studies with a single-stranded DNA probe complementary to the RNA of mouse-tropic AKR murine leukemia virus indicate that the complete genome of the AKR-type murine leukemia virus is present in the DNA of high- and low-virus-yielding mouse strains, while DNA of non-virus-yielding strains contains only a part of the genome. Furthermore, in those strains where the genome is complete, two populations of virus-specific DNA sequences can be identified (more abundant and less abundant species) according to their rate of association with the probe. Low-virus-yielding mouse strains contain fewer copies of the less abundant species and, consequently, fewer complete viral genomes than do high-virus-yielding strains. Thus, in the ten strains tested, there is a good correlation between completeness of the genome of AKR-type murine leukemia virus in cellular DNA and the capacity of the cells to release infectious AKR-type murine leukemia virus. Moreover, the number of complete viral genomes correlates with the frequency of infectious virus production by virus-positive strains. DNA from wild Mus musculus also contained viral sequences, the sample tested showing reassociation kinetics identical to the non-virus-producing strains.

Animals↗

High yield photoreagents for protein crosslinking and affinity labeling.

4-Nitrophenyl ethers are proposed as new high-yield photoreagents for protein crosslinking and affinity labeling. These are totally unreactive in the dark under biological conditions, but react quantitatively with amines at pH 8 upon irradiation with 366-nm light. The reaction of monoalkoxy-p-nitrobenzenes with an amine yields the corresponding free alcohol and substituted nitrophenylamine. In essence, the nitrophenyl group is transferred from the alcohol to the amine. Bifunctional affinity reagents of this type could be especially useful for placing the p-nitrophenyl chromophore adjacent to a binding site without blocking it. The corresponding 2-methoxy-4-nitrophenyl ethers react with amines by displacement of the methoxyl group. Thus, bifunctional reagents of this class could be photocrosslinkers. A maleimide-containing 2-methoxy-4-nitrophenyl ether was attached to human fetal hemoglobin at gamma-cysteine F9 stoichiometrically. Subsequent ultraviolet irradiation yielded a gamma-gamma crosslinked hemoglobin in 80% yield. The oxygenation properties of the derivative indicate that it is locked in a high affinity conformation and that all cooperativity is lost.

Journal Article↗

Comparison of seismic and hydrodynamic yield determinations for the Soviet joint verification experiment of 1988.

Seismic magnitudes determined from surface and body waves for the Soviet underground nuclear explosion of September 14, 1988, are used to calculate the yield of that event from previously derived calibration curves. The yield obtained by combining the two seismic estimates is 113 kilotons, which is very close to those obtained by hydrodynamic measurements made on-site. This comparison substantiates previous conclusions about the sizes of past Soviet weapons tests and compliance with the Threshold Test Ban Treaty. The factor of uncertainty in the combined seismic yield is 1.28 at the 68% and 1.62 at the 95% confidence levels, demonstrating that accuracies considerably better than a factor of 2 can be obtained by combining seismic determinations of yield.

Journal Article↗

Case study of the effects of atmospheric aerosols and regional haze on agriculture: an opportunity to enhance crop yields in China through emission controls?

The effect of atmospheric aerosols and regional haze from air pollution on the yields of rice and winter wheat grown in China is assessed. The assessment is based on estimates of aerosol optical depths over China, the effect of these optical depths on the solar irradiance reaching the earth's surface, and the response of rice and winter wheat grown in Nanjing to the change in solar irradiance. Two sets of aerosol optical depths are presented: one based on a coupled, regional climate/air quality model simulation and the other inferred from solar radiation measurements made over a 12-year period at meteorological stations in China. The model-estimated optical depths are significantly smaller than those derived from observations, perhaps because of errors in one or both sets of optical depths or because the data from the meteorological stations has been affected by local pollution. Radiative transfer calculations using the smaller, model-estimated aerosol optical depths indicate that the so-called "direct effect" of regional haze results in an approximately 5-30% reduction in the solar irradiance reaching some of China's most productive agricultural regions. Crop-response model simulations suggest an approximately 1:1 relationship between a percentage increase (decrease) in total surface solar irradiance and a percentage increase (decrease) in the yields of rice and wheat. Collectively, these calculations suggest that regional haze in China is currently depressing optimal yields of approximately 70% of the crops grown in China by at least 5-30%. Reducing the severity of regional haze in China through air pollution control could potentially result in a significant increase in crop yields and help the nation meet its growing food demands in the coming decades.

Agriculture↗

Growth yield homeostasis in respiring yeast is due to a strict mitochondrial content adjustment.

In living cells, growth is the result of coupling between substrate catabolism and multiple metabolic processes taking place during net biomass formation and cell property maintenance. A crucial parameter for growth description is its yield, i.e. the efficiency of the transformation from substrate consumption to biomass formation. Using numerous yeast strains growing on different respiratory media, we have shown that the growth yield is identical regardless of the strain, growth phase, and respiratory substrate used. This homeostasis is the consequence of a strict linear relationship between growth and respiratory rates. Moreover, in all conditions tested, the oxygen consumption rate was strictly controlled by the cellular content of respiratory chain compounds in such a way that, in vivo, the steady state of oxidative phosphorylation was kept constant. Thus, the growth yield homeostasis depends on the tight adjustment of the cellular content of respiratory chain compounds to the growth rate. Any process leading to a defect in this adjustment allows an energy waste and consequently an energy yield decrease.

Adenosine Triphosphate↗

Prediction of carcase and breast weights and yields in broiler chickens using breast volume determined in vivo by real-time ultrasonic measurement.

1. The use of in vivo real-time ultrasonic (RTU) to predict breast and carcase weights and yields in 103 male broiler chickens was evaluated. Breast area (mm(2)), thickness (mm) and volume (cm(3)) were measured by RTU in three identified sites. After RTU measurements, the broiler chickens were weighed (live weight, LW, g) and slaughtered Carcase and breast weights (g) and physical measures of breast area (mm(2)), and thickness (mm) corresponding to the three identified sites, and volume (cm(3)) were recorded. 2. The best simple correlation between RTU and carcase measurements was obtained for breast volume. Breast and carcase weights were well predicted by LW. Furthermore, breast volume measured in carcase or by RTU was better in predicting breast weight and breast and carcase yields. 3. Multiple regression equations were fitted using LW (g) and RTU measurement of breast volume to predict breast and carcase weights and yields. The coefficients of determination were 0.52 and 0.65 for breast and carcase yields, respectively, and 0.92 and 0.99 for breast and carcase weights, respectively.

Animals↗

The bovine pituitary-adrenocortical axis and milk yield.

A review is given of the available literature concerning the relationship between the bovine pituitary-adrenocortical axis and milk yield in dairy cattle. A severe drop in milk yield (more than 50%) can be induced by a single or repeated intramuscular injection of at least 200 IU ACTH or by a single intramuscular injection of 14.6 mg dexamethasone. Sixty minutes after an intravenous injection, both 200 IU ACTH and 100 mg cortisol are equivalent to a plasma cortisol concentration of at least 31 ng/ml. Thus the decrease in milk yield after an intramuscular injection of more than 200 IU ACTH can hardly be induced by cortisol only. The fact that bovine plasma hardly binds any dexamethasone, in sharp contrast with bovine mammary epithelial tissue, is a possible explanation of the special part which dexamethasone plays in milk yield.

Adrenal Cortex Hormones↗