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Telomere shortening in peripheral blood cells was related with aging but not with white blood cell count.

Telomeres in somatic cells are progressively shortened with aging. We investigated the relationship between the telomere length and other factors which may affect the frequency of cell divisions, in peripheral blood cells. Shortening of telomeric repeats was correlated with aging (p < 0.0001), but not with white blood cell count, neutrophil count, and smoking habit. Not only the number of cell divisions, but also some other factors, such as upregulation level of telomerase activity concomitant with the cell division in hematopoietic progenitor cells, might affect the length of telomeric repeats in blood cells.

Adult↗

Optimal frequency of CD4 cell count and HIV RNA monitoring prior to initiation of antiretroviral therapy in HIV-infected patients.

CONTEXT: Guidelines regarding the frequency of CD4 cell count and HIV RNA monitoring in HIV-infected patients vary, with recommended strategies ranging from every 2 to every 6 months. OBJECTIVE: To determine optimal CD4 cell count and HIV RNA monitoring frequency in HIV-infected patients prior to antiretroviral therapy initiation. DESIGN: Cost-effectiveness (CE) analysis using an HIV simulation model incorporating CD4 cell count and HIV RNA as immunological and virological predictors of clinical outcomes. SETTING: Hypothetical clinical setting. PATIENTS: Simulated cohort based on initial clinical presentation of HIV-infected patients in the US. INTERVENTION: CD4 cell count and HIV RNA monitoring at frequencies ranging from every 2 to 24 months prior to antiretroviral initiation, as well as accelerated monitoring frequencies as CD4 cell counts approach a specified treatment threshold. OUTCOME MEASURES: Life expectancy, quality-adjusted life expectancy and costs. RESULTS: For patients presenting with median CD4 cell count 546/mm3 and median HIV RNA 4.8 log10 copies/ml, incremental CE ratios ranged from US$37800/quality-adjusted life year (QALY) gained for a constant testing frequency of every 18 months compared with every 24 months, to US$303300/QALY gained for a constant testing frequency of every 2 months compared with every 4 months when starting treatment at a CD4 cell count of 350/mm3. Monitoring every 12 months until a warning CD4 cell count threshold of 450/mm3 followed by every 3 months until 350/mm3 had an incremental CE ratio of US$74700/QALY gained. When starting antiretroviral therapy at CD4 cell count 200/mm3, monitoring every 12 months until 300/mm3 followed by every 2 months until treatment initiation yielded an incremental CE ratio of US$52200/QALY gained compared with the next best strategy. Increasing monitoring frequency as CD4 cell counts approached a treatment threshold yielded greater incremental clinical benefit for less cost than strategies using a constant frequency. CONCLUSIONS: Monitoring HIV-infected patients every 12 months until 100 CD4 cells/mm3 prior to a specified treatment threshold followed by more frequent monitoring every 2 or 3 months until antiretroviral therapy initiation is both more effective and cost-effective than the current standard of care.

Anti-HIV Agents↗

White cell count and intensive care unit outcome.

A high white cell count on admission to the intensive care unit (ICU) is generally perceived to be associated with severe illness and poor outcome, but the implications of a low white cell count are less well recognised. We retrospectively analysed data on 4,165 patients. The white cell count on admission was split into four categories, leucopenic (< 4.0 x 10(9).l(-1)), normal (4.001-10.0 x 10(9).l(-1)), leucemoid (10.001-25.0 x 10(9).l(-1)) and an exaggerated leucemoid response (> 25.001 x 10(9).l(-1)). The mortality of patients with leucopenia on admission to the intensive care unit was higher than those with normal or moderately raised white cell count (37.5% vs. 18.9% and 23.9%, respectively). A leucopenic response, as well as an exaggerated leucemoid response, is associated with an increased mortality.

APACHE↗

Significance of high and normal neonatal nucleated red blood cell count in small-for-gestational-age newborns.

The objective of this study was to evaluate the obstetrical and neonatal outcome in small-for-gestational age (SGA) and appropriate-for-gestational-age (AGA) fetuses with normal and elevated neonatal nucleated red blood cell counts. Therefore the nucleated red blood cell count was assessed immediately after birth in 906 neonates delivered at our institution and the perinatal and neonatal data were compared. Postnatally, infants were classified as SGA if they had a birth weight for given gestational age below the 10th percentile. Neonates were allocated to four groups according to their nucleated red blood cell count: SGA neonates with normal and high nucleated red blood cell count and appropriate-for-gestational-age newborns (AGA) with normal and high nucleated red blood cell count. Statistical analysis included the Mann-Whitney U-Test, Student's t-test, chi2 analysis of variance and stepwise regression analysis. SGA newborns with high nucleated red blood cell count had a significantly lower birth weight, a lower gestational age at delivery, lower arterial and venous pH values, lower Apgar scores at 1 min, 5 min and 10 min as well as lower base excess values compared to the other groups. They had to be transferred significantly more often and stayed longer in the neonatal intensive care unit. Three cases of intraventricular hemorrhage, four cases of necrotizing enterocolotis and two neonatal deaths occurred all in the SGA group with high neonatal nucleated red blood cell counts. Neonatal outcomes of SGA and AGA newborns with normal nucleated red blood cell counts were comparable. Our data do therefore underline the possible value of neonatal nucleated red blood cell counts to differentiate the healthy small-for-gestational age newborn from the truely growth retarded newborn.

Apgar Score↗

Genetics statistics and relationships of teat and udder traits, somatic cell counts, and milk production.

Teat lengths and diameters, udder clearance, cleft depth, and distances between teats were measured from 1967 to 1982 on Holstein cows. Numbers of observations per trait ranged from 5934 to 11,449. Cows were from six herds owned by the North Carolina Department of Agriculture and two research herds of North Carolina State University. Repeatabilities between adjacent lactations for physical traits of udder were mostly between .60 and .80. Repeatabilities between first and second lactations for average somatic cell count and mean log somatic cell count were .11 +/- .04 and .21 +/- .04. Heritabilities in first lactation were .63 for front teat length, .44 for teat diameter, .56 for rear udder clearance, .10 for cleft depth, .32 for mature equivalent milk, and .18 for somatic cell counts. Heritabilities of distances between teats ranged from .33 to .48. Cows with udder clearance higher from the ground, deeper clefts, smaller distances between teats, and teats of smaller diameter had lower somatic cell counts. Multiple regression analysis showed that dams' somatic cell counts and rear udder clearances were not significant predictors of daughters' somatic cell counts. Lactation average somatic cell counts of daughters were predicted with greater accuracy from averages of somatic cell counts of multiple lactations of dams than from single lactations of dams. Milk production and somatic cell counts seemed positively genetically correlated, more so in first than later lactations.

Animals↗

Predictive value of absolute CD4 cell count for disease progression in untreated HIV-1-infected children.

OBJECTIVES: To describe the relationship between absolute CD4 cell count and the short-term risk of disease progression in HIV-1-infected children. DESIGN: A meta-analysis of individual longitudinal data on HIV-1-infected children enrolled in trials and cohort studies in Europe and the USA. METHODS: The risks of progression to death and AIDS (or death) within 12 months, in terms of age and the most recent CD4 cell count, were estimated using parametric survival models. The analysis was restricted to measurements before the start of antiretroviral therapy except zidovudine monotherapy. The values of the absolute CD4 cell count and percentage predicting selected levels of disease progression risk were determined from this and previous models. RESULTS: A total of 566 deaths was observed over 9128 person-years of follow-up, and 992 children progressed to AIDS or death over 7309 person-years of follow-up. In children older than 4 or 5 years, the estimated risk of disease progression increased sharply when the CD4 cell count fell below 200-300 cells/microl. As with other immunological markers, CD4 cell count was less prognostic in younger children. The CD4 cell count values predicting a 12-month risk of death of 2-5% and of AIDS of 5-10% were much more strongly influenced by age than equivalent CD4 cell percentage values. CONCLUSION: This study suggests it may be appropriate to extend CD4 cell count criteria for initiating antiretroviral therapy in HIV-1-infected adults to children as young as 4 or 5 years. Monitoring by CD4 cell count in younger children is problematical because age is a highly influential variable.

Anti-Retroviral Agents↗

[JCCLS proposal for clinical allowance on values of blood cell count].

We investigated the clinically allowable error for laboratory quality control of blood cell count in Japan. We have asked 409 members of Japanese Association of Clinical Hematology for an appropriate clinical allowance on the values of red blood cell count (RBC), hemoglobin value (Hb), mean corpuscular volume (MCV), white blood cell count (WBC) and platelet count (PLT). We delivered the lists in which 5 different allowable errors (2, 3, 5, 10 and 20%) were indicated on each blood cell count so that each member could check one of them. The data were collected within a month and were analyzed with computer. The results showed that 312 (76.3%) members choose 3 or 5% as an allowable error for RBC, 393 (96.1%) selected 2, 3 or 5% for Hb, 314 (76.8%) choose 3 or 5% for MCV, 358 (77.5%) indicated 3, 5 or 10% for WBC and 294 (72.6%) selected 5 or 10% for PLT. Based on these data, we propose the following clinical allowances for the values of blood cell count; 4% for RBC, 3% for Hb, 4% for MCV, 5% for WBC and 7% for PLT.

Blood Cell Count↗

Rate, causes, and clinical implications of presenting with low CD4+ cell counts in the era of highly active antiretroviral therapy.

Of patients attending HIV clinics, neither the proportion with CD4(+) cell counts below 200 cells/microl, and therefore at risk for developing opportunistic infections (OIs), nor the reasons for the persistence of low CD4(+) cell counts are well known in the era of highly active antiretroviral therapy (HAART). In an effort to gather data concerning this issue, the charts of all outpatients who attended two reference HIV clinics in Spain throughout the year 2001 were retrospectively reviewed. Of 1897 subjects, 213 (11%) had at least one CD4(+) cell count determination below 200 cells/microl during 2001. The main reasons for presenting with low CD4(+) cell counts were as follows: (1) poor treatment adherence, 64 (30%); (2) poor immune recovery despite complete virus suppression for longer than 1 year on HAART, 47 (22%); (3) virologic failure under HAART, 33 (15%); (4) no antiretroviral therapy, 23 (11%); (5) initiation of HAART within the current year in subjects with very low CD4(+) cell counts, 17 (8%); (6) impediment in using HAART due to toxicity, 17 (8%); and (7) drug-induced myelotoxicity, 12 (6%). During the period under review, one or more OIs developed in 52 of the 213 (24%) patients with low CD4(+) cell counts. They occurred more frequently in subjects who were naive for antiretroviral drugs or who initiated therapy recently (RR, 6.45; 95% CI, 2.43-17.12; p < 0.001), and conversely tended to be less frequent among subjects with poor immune reconstitution despite complete virologic suppression while on HAART (RR 0.86; 95% CI, 0.28-2.62; p = 0.79). A lower lifetime CD4(+) cell count nadir was associated with a greater risk of developing an OI (RR, 0.98; 95% CI, 0.97-0.99; p < 0.001). We conclude that, despite the availability of HAART, more than 10% of patients currently attending HIV clinics have CD4(+) cell counts <200 cells/microl, and continue to be at risk for developing OIs. Poor treatment adherence and lack of immune recovery despite complete virus suppression while on HAART account for more than half of cases.

AIDS-Related Opportunistic Infections↗

Impact of 5 years of maximally successful highly active antiretroviral therapy on CD4 cell count and HIV-1 DNA level.

OBJECTIVES: To evaluate the impact on CD4 cell count and HIV-1 DNA level in peripheral blood mononuclear cells (PBMC) of long-term highly active antiretroviral therapy (HAART) in the setting of maximal success, i.e., constant plasma HIV-1 RNA load suppression. DESIGN: Retrospective analysis of patients selected for a constantly undetectable plasma HIV-1 RNA load since HAART initiation. METHODS: HIV-1 DNA was measured in PBMC using a real-time polymerase chain reaction assay. Loess estimates and regression analysis were used for modelling the variations of the CD4 cell count and HIV DNA level over time. RESULTS: The study included 41 patients chronically infected with HIV-1 who had been taking HAART for a median duration of 60.4 months and had an undetectable plasma HIV RNA load ever since the first 6 months of HAART; 25 were tested for HIV-1 DNA. The mean CD4 cell count increase was high during the first 18 months on therapy (168 x 10 cells/l per year), much lower afterwards (38 x 10 cells/l per year), independently of the baseline CD4 cell count. Most of the patients (73.2%) reached a CD4 cell count constantly > or = 400 x 10/l during follow-up. HIV-1 DNA showed a mean decrease of 0.48 log10 copies/10 PBMC during the first year, of 0.18 log10 copies/10 PBMC per year during the 2nd and 3rd years, but no significant decrease afterwards. CONCLUSIONS: These results question the benefit of very long-term maintenance of HAART in terms of CD4 gain and HIV-1 DNA reduction.

Adult↗

Acute effects of single doses of recombinant interferon-gamma on blood cell counts and lymphocyte subsets in patients with advanced renal cell cancer.

The object of this study was to investigate the effects of different single doses of recombinant interferon-gamma (rIFN-gamma) on white blood cell counts, differential blood counts, and the relative composition of T-cell subsets in the peripheral blood of cancer patients. Sixteen patients suffering from metastasizing renal cell carcinoma received 10, 100, or 500 micrograms of rIFN-gamma three times at weekly intervals. After a therapy-free interval of 2 weeks, the next dose level was applied. The order of dose levels was assigned randomly to each patient. White blood cells, differential blood counts, and the number of Leu1, Leu3, Leu2a, Leu7, and HLA DR+ cells were measured immediately before and at 4, 24, 48, 72, 96, and 168 h after the administration of single doses of rIFN-gamma. Results indicated that white blood cells were transiently removed from the blood circulation after administration of IFN-gamma. Monocytes, HLA DR+ cells, and Leu7+ cells were reduced to below 50% of pretreatment values 4 h after application of the cytokine. CD8+ cells and granulocyte counts declined to approximately 70% of pretreatment values 24 h after IFN therapy. The preferential reduction of CD8+ lymphocytes resulted in a temporary increase of the T4/T8 ratio in these patients.

Adult↗

Genetic and phenotypic statistics of lactation cell counts in different lactations of Holstein cows.

Between February 1977 and February 1982, 680,246 monthly test-day observations of somatic cell count were taken for Holstein cows having completed 79,124 lactations in 941 herds on the Quebec Dairy Herd Analysis Service. Data were transformed to natural log scale, and analyses were separate within five parity groups. Two lactational measures of cell count, geometric mean, and weighted (by test-day milk yield) mean of the log of monthly cell counts were calculated for each lactation. Maximum likelihood, iterative Minimum Norm Quadratic Unbiased Estimation, and multivariate Restricted Maximum Likelihood procedures were used for estimation of genetic and phenotypic parameters. Repeatabilities of log test-day cell counts and log of test-day cell counts corrected for milk yield were the same at each parity, .36, .41, .42, .42, and .42 in first, second, third, fourth, and fifth and later parities. Repeatabilities of lactational measures of cell count were .33 between first and second parities, .40 between second and third parities, .13 between first and third parities, and .27 between first, second, and third parities. Heritabilities of measures of lactational cell count were small from .06 to .14 in the five parities. Genetic correlations between measures of lactational cell count in different parities were close to unity, .90 to .97.

Animals↗

CD4 cell count recovery among HIV-infected patients with very advanced immunodeficiency commencing antiretroviral treatment in sub-Saharan Africa.

BACKGROUND: Patients accessing antiretroviral treatment (ART) programmes in sub-Saharan Africa frequently have very advanced immunodeficiency. Previous data suggest that such patients may have diminished capacity for CD4 cell count recovery. METHODS: Rates of CD4 cell increase were determined over 48 weeks among ART-naïve individuals (n = 596) commencing ART in a South African community-based ART programme. RESULTS: The CD4 cell count increased from a median of 97 cells/microl at baseline to 261 cells/microl at 48 weeks and the proportion of patients with a CD4 cell count < 100 cells/microl decreased from 51% at baseline to just 4% at 48 weeks. A rapid first phase of recovery (0-16 weeks, median rate = 25.5 cells/microl/month) was followed by a slower second phase (16-48 weeks, median rate = 7.7 cells/microl/month). Compared to patients with higher baseline counts, multivariate analysis showed that those with baseline CD4 counts < 50 cells/microl had similar rates of phase 1 CD4 cell recovery (P = 0.42), greater rates of phase 2 recovery (P = 0.007) and a lower risk of immunological non-response (P = 0.016). Among those that achieved a CD4 cell count > 500 cells/microl at 48 weeks, 19% had baseline CD4 cell counts < 50 cells/microl. However, the proportion of these patients that attained a CD4 count 200 cells/microl at 48 weeks was lower than those with higher baseline CD4 cell counts. CONCLUSION: Patients in this cohort with baseline CD4 cell counts < 50 cells/microl have equivalent or greater capacity for immunological recovery during 48 weeks of ART compared to those with higher baseline CD4 cell counts. However, their CD4 counts remain < 200 cells/microl for a longer period, potentially increasing their risk of morbidity and mortality in the first year of ART.

Adult↗

Do blood cell counts have an independent prognostic value in primary lung cancer?

A review of the biomedical literature suggests that lymphocyte and neutrophil counts are probably the only blood cell count parameters whose independent pre-therapeutic prognostic values are significantly documented in lung cancer (and only in non small cell lung cancer). The independent pre-therapeutic prognostic value of these two parameters remains quite controversial however, and further studies should be conducted, and in particular, comparisons between neutrophils, lymphocytes, and serum cyfra 21-1. For the therapeutic follow-up, further prognostic evaluation studies are also necessary for blood cell count parameters as well as for serum cyfra 21-1. Clinical biologists still have to convince clinicians and/or journal editors that it is not scientifically acceptable for publications to omit detailing the analytical and pre-analytical methodologies used for blood cell count measurements.

Blood Cell Count↗

A clinical trial to evaluate the effectiveness of antibiotic treatment of lactating cows with high somatic cell counts in their milk.

OBJECTIVE: To determine the effectiveness of treatment of lactating cows with high somatic cell counts in milk. DESIGN: Randomised clinical trial. METHODS: Single pooled quarter samples of milk were obtained from cows with somatic cell counts above 500,000 cells/mL on fifty farms. Milk samples were cultured for known mastitis bacterial pathogens. Cows were randomly allocated to treated and untreated groups. Treated cows received both intramammary cloxacillin and parenteral erythromycin. Single pooled quarter milk samples were obtained at 6 weeks after treatment and were cultured for the presence of pathogenic bacteria. The percentage of samples with no growth at the post-treatment culture was used as an estimate of the bacteriological cures for each pathogen type and for each treatment group. Somatic cell counts of cows were compared between treatment groups and within pathogen group. The number of cows that completed a full lactation were compared between each treatment group and within each pathogen group. RESULTS: Treatment had no effect upon bacteriological cures, irrespective of pathogen present or the presence of bacteria during the previous lactation. There was no effect of treatment upon somatic cell count except for cows infected with Streptococcus dysgalactiae in which treatment caused a significant lowering of cell counts. This effect was not present in the subsequent lactation. Treatment of chronically infected cows did not alter the probability of a cow completing a full lactation but did improve the probability of newly infected cows being retained for the next lactation. Twenty-eight of 214 treated cows developed clinical mastitis in more than one quarter after treatment, thus indicating a poor technique by farmers for the insertion of intramammary antibiotics. CONCLUSIONS: Treatment during lactation of cows with high somatic cell counts in milk is ineffective in reducing bacterial infections and in reducing somatic cell counts to acceptable numbers.

Animals↗

CD4 cell counts in adults with newly diagnosed HIV infection: results of surveillance in England and Wales, 1990-1998. CD4 Surveillance Scheme Advisory Group.

OBJECTIVES: To describe the distribution and changes in CD4 cell counts (both initial and subsequent) in HIV-infected persons over time and determine the factors influencing these counts. DESIGN: Reports were requested from laboratories measuring CD4 cell counts in England and Wales. Initial counts were analysed and median counts were followed over time. METHODS: Time trends and the relationship between initial CD4 cell count and age, sex, and HIV risk category were studied using quantile regression methods or chi-square tests. RESULTS: Between 1990 and 1998, 9553 adults were newly diagnosed with HIV infection and had a CD4 cell count within 6 months of HIV diagnosis. Over 50% of initial CD4 cell counts in each major risk category were below 350 cells/mm3. Older age (P < 0.001), male sex (P < 0.013) and heterosexual risk (P < 0.001) were independently associated with lower initial CD4 cell counts. For heterosexually infected adults, the median initial CD4 cell count was significantly negatively associated with the year of diagnosis (P = 0.03) and the median age increased through the time period examined (P < 0.001), whereas for men who have sex with men (MSM), there was no significant change in these values over time. For each year cohort of newly diagnosed individuals, the median CD4 cell count in subsequent years decreased until 1996 and then increased thereafter, consistent with a treatment effect. CONCLUSION: Across all major risk groups, a large proportion of HIV-infected adults are being diagnosed late in the course of HIV disease. For the heterosexually infected, the data suggest an ageing cohort effect, whereas for MSM the data are consistent with continuing transmission.

Adult↗

Nucleated red blood cell count in the differentiation of fetuses with pathologic growth restriction from healthy small-for-gestational-age fetuses.

OBJECTIVE: The purpose of this study was to evaluate the utility of the neonatal nucleated red blood cell count in differentiating the fetus with growth restriction from the small but otherwise healthy fetus. STUDY DESIGN: Perinatal outcomes were evaluated prospectively for all neonates admitted to the neonatal intensive care unit in 1997. Nonanomalous neonates with normal phenotype and a complete blood cell count performed within the first 6 hours after birth were included in the study. All neonates with birth weights lower than the 10th percentile for gestational age were considered small for gestational age. Neonates were divided into four groups: small-for-gestational-age neonates with elevated nucleated red blood cell counts, appropriately grown neonates with elevated nucleated red blood cell counts, small-for-gestational-age neonates with normal nucleated red blood cell counts, and appropriately grown neonates with normal nucleated red blood cell counts. Analysis of variance, chi(2) tests, and stepwise regression were used for statistical analysis. RESULTS: Two hundred thirty-seven neonates met the inclusion criteria. Forty-three were small for gestational age. Small-for-gestational-age neonates with high nucleated red blood cell counts had significantly lower umbilical artery pH and were more likely to require mechanical ventilation or blood pressure support agents. Subgroup analysis demonstrated that small-for-gestational-age neonates with elevated nucleated red blood cell counts had significantly more adverse outcomes than did small-for-gestational-age neonates with normal nucleated red blood cell counts. Outcomes of small-for-gestational-age neonates with normal nucleated red blood cell counts were essentially identical to those of appropriately grown neonates. CONCLUSION: An elevated nucleated red blood cell count may distinguish the fetus with growth restriction from the small but healthy fetus.

Erythroblasts↗