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Effect of moderate exercise on immune senescence in men.

The purpose of this study was to examine the relationship between active compared to inactive lifestyles and immunocompetence in men. Subjects, all male volunteers, regularly exercising moderately were separated into three age groups: young (20-39 years), middle-aged (40-59 years) and elderly (more than 60 years). Age-matched sedentary male subjects served as controls in each group. Immunological assessments were, total leucocyte count, lymphocyte subpopulation counts, natural killer cell activity and neutrophilic phagocytosis. Total leucocyte and T-cell (CD3+) counts were not significantly different among the groups. Among T-cell subsets, there was a slight increase in helper T-cell (CD3+CD4+) and a decrease in cytotoxic/suppressor T-cell (CD3+CD8+) concentrations in the older sedentary subjects, resulting in an age-associated significant increase in the CD4:CD8 ratio among those control groups. However, among the exerciser groups, no such increase and decrease in the T-cell subpopulations or an age-related increase of the CD4:CD8 ratio were observed. Considering the components of innate immunity, the concentration of NK-cells (CD16+CD56+) significantly increased in the elderly exercisers, compared to that of the age-matched control subjects, or of the young group. The phagocytotic activity of neutrophils showed an age-associated decline, but of lesser degree in the elderly exercisers than in the elderly controls. Taken together, these results suggest that habitual and moderate training in later life is associated with a lesser age-related decline in certain aspects of circulating T-cell function and innate immunity.

Adult↗

Bronchoalveolar lavage (BAL) in miliary tuberculosis.

We report bronchoalveolar lavage (BAL) cellular analysis in eight patients with miliary tuberculosis. The total cell count and lymphocytes count of BAL fluid were significantly increased and the alveolar macrophage count was significantly decreased in patient with miliary tuberculosis compared to normal subjects. Epithelioid cell granulomas were seen in BAL fluid in two patients.

Adult↗

Pilot study of rapid steroid elimination with alemtuzumab induction therapy in kidney and pancreas transplantation.

This study evaluates our initial experience using alemtuzumab induction with rapid corticosteroid elimination in kidney (KTX) and pancreas transplant (PTX) patients. Data were collected retrospectively for all patients who received single-dose alemtuzumab (30 mg IV intraoperatively) with steroid pretreatment and a control group who received alternate day rabbit antithymocyte globulin (rATG) induction with a steroid-based regimen. Patients in both groups received tacrolimus (TAC) and mycophenolate mofetil (MMF). There were 16 patients in each group, including 9 deceased donor KTXs, 5 living donor KTXs, 1 simultaneous K-PTX, and 1 sequential PTX after KTX. Demographic, immunologic, and transplant characteristics were similar between groups. Nine patients (56%) in the alemtuzumab group compared to five (25%) in the control group developed neutropenia requiring MMF or valganciclovir dose reduction (or both). Absolute lymphocyte counts at 3 months were 340 +/- 200/mm3 and 890 +/- 544/ mm3 in the alemtuzumab and control groups, respectively (P = .001). There were two biopsy-proven acute rejection episodes (12.5%) in each group, and no difference in the incidence of infection. Creatinine clearance at 6 months was 58 mL/min in each group. Patient and kidney graft survival rates were both 94% in the alemtuzumab group (one death from cardiac arrest), compared with 100% patient and kidney graft survival rates in the control group (P = NS), with a mean follow-up of 9 and 11 months, respectively. The results of this pilot study suggest that similar short-term outcomes can be achieved using a rapid steroid elimination protocol with alemtuzumab induction therapy compared to rATG with steroids in patients receiving TAC and MMF maintenance therapy.

Adrenal Cortex Hormones↗

Menopause is associated with a significant increase in blood monocyte number and a relative decrease in the expression of estrogen receptors in human peripheral monocytes.

PROBLEM: The clinical significance of the differential expression of estrogen receptor (ER) in human monocytes was evaluated. METHOD: Two color flow cytometry analysis was used on peripheral blood samples of young and postmenopausal females and postmenopausal females treated with estrogen replacement therapy. In addition, the monocyte and lymphocyte counts and the blood estrogen levels of each patient were determine. RESULTS: During menopause there is a significant decrease in the percentage of ER positive monocytes, and an increase in blood monocyte number, which declines following estrogen replacement therapy to values of the young. CONCLUSIONS: These findings suggest that estrogen modulates the monocyte numbers and its effects may be mediated through the ER in the monocytes.

Adolescent↗

Hematopoietic responses to stress conditions in young dogs compared with elderly dogs.

Clinical observations show that older patients do not tolerate high-dose chemoradiotherapy as well as younger patients. It is unclear whether this is due to age-related differences in their responses to hematopoietic injury or to differential toxicities to other organs. In the present study, 6 young (0.5 years) and 6 elderly (8 years) dogs were challenged with 7 repeated nonlethal doses of 50 or 100 cGy total body irradiation (TBI) each (total 550 cGy), and 21 days of recombinant canine granulocyte-colony stimulating factor (rcG-CSF) after the last TBI dose. Recoveries of absolute neutrophil, platelet, and lymphocyte counts after each TBI dose, responses to rcG-CSF treatment, and telomere lengths in neutrophils were compared before and after the study. No differences were found in recoveries of neutrophils, platelets, or in responses to rcG-CSF among young and old dogs. In contrast, recoveries were suggestively worse in younger dogs. After rcG-CSF, platelet recoveries were poor in both groups compared with previous platelet recoveries (P <.01). Consequently, 2 old and 3 young dogs were euthanized because of persistent thrombocytopenia and bleeding. At the study's completion, marrow cellularities and peripheral blood counts of the remaining young and elderly dogs were equivalent. The telomere lengths in both groups were significantly reduced after the study versus beforehand (P =.03), but the median attritions of telomeres were not different. It was concluded that aging does not appear to affect hematopoietic cell recoveries after repeated low-dose TBI, suggesting that poor tolerance of radiochemotherapy regimens in older patients may be due to nonhematopoietic organ toxicities rather than age-related changes in hematopoietic stem cells reserves.

Aging↗

[Effects of lifestyle on hematologic parameters; I. Analysis of hematologic data in association with smoking habit and age].

The effects of smoking and age on the results of hematologic tests were determined in a group of 429 healthy male workers. The results obtained were as follows: 1) The values of total leucocyte count (x10(9)/l), neutrophil count (x10(9)/l), lymphocyte count (x10(9)/l), monocyte count (x10(9)/l), hemoglobin (g/l), hematocrit, mean corpuscular volume (MCV; fl), mean corpuscular hemoglobin (MCH; pg), and mean corpuscular hemoglobin concentration (MCHC; g/dl) in current smokers were significantly higher than those in non-smokers. 2) Total leucocyte counts and neutrophil counts significantly increased with the number of cigarettes smoked per day in current smokers. 3) Total leucocyte counts, neutrophil counts, and lymphocyte counts significantly increased with Brinkman Index (B.I.) in current smokers. 4) The increase of age was significantly associated with the decrease of erythrocyte counts and the increase of MCV in both current smokers and non-smokers.

Adolescent↗

Bacteraemia in neonatal foals: clinicopathological differences between Gram-positive and Gram-negative infections, and single organism and mixed infections.

REASONS FOR PERFORMING STUDY: Treatment for bacteraemia in foals must be started before the identity of the causative organism is known. Information aiding selection of effective antimicrobials should improve outcome. OBJECTIVES: To describe differences in clinical and clinicopathological data and outcome in foals with bacteraemia due to different classes of bacteria. METHODS: Records of foals with a positive blood culture, age < 10 days and presenting to a university hospital 1995-2004, were reviewed. Bacterial culture results, subject details, historical information, physical examination findings at admission and clinicopathological data generated during the first 48 h of hospitalisation were analysed. Results from foals with Gram-positive or Gram-negative organisms, single or mixed organism bacteraemias, and with bacteraemia due to 3 commonly isolated organisms were compared. RESULTS: Eighty-five foals met the inclusion criteria. Gram-negative organisms (n = 59) Gram-positive organisms (n = 13) or multiple organisms (n = 19) were cultured from individual foals. Foals with Gram-negative bacteraemia had lower total white blood cell and lymphocyte counts at admission than did those from which only Gram-positive bacteria were cultured. Mixed organism bacteraemia was associated with tachycardia, increased serum concentrations of sodium, chloride and urea nitrogen, acidosis, respiratory distress, recumbency on admission and nonsurvival. Actinobacillus spp. infections were associated with leucopenia, neutropenia, lymphopenia and depression on hospital admission. CONCLUSIONS AND POTENTIAL RELEVANCE: Recognising particular patterns of clinical and clinicopathological findings associated with infection with specific groups of bacteria may, in the future, aid antimicrobial selection and influence prognosis in bacteraemic foals.

Animals↗

Effect of exogenous somatotropin on hematological variables of lactating cows and their offspring.

Eighty-two lactating Holstein cows in their first, second, or third lactation received either one, three, or five concurrent i.m. injections of a unit dose (0.6 g) of zinc methionyl bovine somatotropin (bST) or five doses of the vehicle. Injections were administered at 14-d intervals from 60 +/- 3 d postpartum until the end of lactation or until necropsy. Thirty-eight cows were continued on the treatment for a 2nd yr. Blood samples were collected at wk -2, -1, 3, and 7 relative to the start of treatment and then every 8 wk (yr 1) or 4 wk (yr 2) thereafter. Untreated cows that were included in a survey of the resident herd were bled at wk 7 or 8, wk 10 or 11, and wk 13 or 14 of lactation and every 4 or 8 wk thereafter. Calves were bled within 72 h of birth and at approximately 5 wk of age. Most parameters associated with erythrocytes were decreased mildly in cows that were treated with bST. However, data remained within generally accepted reference ranges, and changes were not of clinical importance. Decreased hematocrit was not associated with increased hemolysis, hemodilution, or clinical anemia. No morphological lesions related to treatment were noted in the bone marrow or spleen; bST did not affect the incidence of immature cell types. Energy and protein balances did not significantly affect the hematological results of the cows. Calves generally were unaffected by bST treatment of the dam, but heavier calves had higher parameters associated with erythrocyte and lymphocyte counts than did calves with lower body weight. Exogenous bST treatment caused predictable changes in hematological parameters of dairy cows.

Animals↗

Immune reactivity and clinical stage of patients with laryngeal cancer.

Selected parameters of the immune system were determined in vivo and vitro in 200 patients with malignant tumours of the larynx in various stages of clinical progression before surgical treatment. The comparison of the results with those in control groups of healthy persons made division of the patients possible into groups (a, b, c, d), and statistical analysis of the differences. The distribution of the patients according to the mean values of these parameters showed that such parameters as: white blood cell count, absolute lymphocyte count, absolute granulocyte count, receptor activity of T-cells and enzymatic activity of peripheral blood neutrophils may have characteristic values in laryngeal cancer. Particularly significant from the standpoint of prognostic value were the results of delayed hypersensitivity response to protein pure derivative (PPD), phytohaemagglutinin (PHA) and streptokinase-streptodornase (SK-SD).

Granulocytes↗

Characteristics of toxic epidermal necrolysis in patients undergoing long-term glucocorticoid therapy.

BACKGROUND AND DESIGN: The usefulness of steroid therapy in toxic epidermal necrolysis (TEN) remains controversial. Up to 5% of the TEN cases occur in patients who undergo long-term steroid therapy. We, thus, looked for the potential effect of long-term glucocorticosteroid therapy before the onset of TEN on altering the progression of the disease. The records of 179 patients were reviewed. The characteristics of the 13 patients who were undergoing long-term glucocorticosteroid therapy were compared with those of 166 other patients with TEN. The following parameters were studied: age, mortality, delay between the introduction of the suspect drug and the onset of TEN, length of hospital stay, body surface area involved, time elapsed between the first symptom of TEN and hospital admission, number of medications taken by the patients before the onset of TEN, lymphocyte count, granulocyte count, platelet count, glycemia, serum aspartate aminotransferase level, and total disease duration. RESULTS: Patients who were undergoing long-term glucocorticosteroid therapy differed from other patients with TEN in the administration of more drugs, longer delay between the introduction of the suspect drug and the onset of TEN, and a longer time elapsed between the first symptom of TEN and hospital admission. We observed no differences for the other parameters that were studied. CONCLUSION: Our study shows that long-term steroid therapy may delay the onset of TEN, but it does not halt its progression.

Adolescent↗

Absolute lymphocytopenia as a diagnostic aid in bronchogenic carcinoma.

Total lymphocyte count and lymphocyte percentage were calculated in a group of 26 patients of Bronchogenic carcinoma and compared with the values in 22 cases of pulmonary tuberculosis. Patients of Bronchogenic carcinoma had a significant lymphocytopenia as compared to patients of tuberculosis. It is inferred that this peripheral lymphocytopenia can be used as a possible diagnostic pointer in patients of Bronchogenic carcinoma.

Carcinoma, Bronchogenic↗

Evaluating efficiency of bone marrow harvest and its manipulation--role of CD 34 positivity.

We evaluated harvested marrow cells for total nucleated cells (27.49 x 10(9)), absolute 'lymphocyte' count (6.29 x 10(9)) and CD 34 positive cells (3.57 x 10(9)). The same parameters were studied after in vitro manipulation to remove RBCs and plasma. Reinfused WBCs contained 12.87 x 10(9) nucleated cells, 4.25 x 10(9) absolute 'lymphocyutes' and 3.34 x 10(9) CD 34 positive cells. The corresponding figures for loss during in vitro manipulation (tubing, RBCs and plasma) are 14.62 (53.18%), 2.04 (32.43%) and 0.23 x 10(9) (6.44%) cells respectively. Therefore CD 34 positivity may be a better indicator of total yield, loss during manipulation and reinfusion of hemopoietic progenitor cells in bone marrow transplantation.

Antigens, CD34↗

Significance of tumour mass on T-lymphocyte levels in patients with gastrointestinal cancer.

The relationship between tumour load and immunity in gastrointestinal cancer has been studied by sequential comparison in patients whose tumour has been removed and those whose tumour was found to be inoperable. Total lymphocyte count, absolute and percentage T- and B-lymphocyte counts, effect of papain on E-rosetting cell levels, and inhibitory effect of cancer sera on E-rosette formation by normal lymphocytes have been studied in 30 patients with stomach or colorectal cancer, and 10 control patients with benign gastrointestinal disease. The examination was done on each patient before and at regular intervals after operation up to 24 weeks. Operable cases, with removal of tumour load, showed a temporary fall in total lymphocyte count and T cell counts, which returned to normal by four weeks postoperatively. Inoperable cases (15 patients) showed a progressive fall in total lymphocyte count and a relatively greater depression of T cell counts, in parallel with increasing tumour mass. E-receptor blocking factor was demonstrated in the sera of cancer patients. This factor was related to tumour mass and presumably was of tumour origin, as it persisted in the inoperable group but disappeared by 12 weeks after tumour removal. The factor explained the excess depresion of T cells over total lymphocytes, but does not explain the continuing depression of total lymphocyte count in the cancer patients.

Aged↗

Circannual variation in lymphocyte subsets, revisited.

BACKGROUND: Circadian and circannual variations in lymphocyte subsets, especially CD8+ T-lymphocytes, have been reported. This study focuses on CD4+ T-lymphocyte seasonal variation over a 6-year 8-month period. STUDY DESIGN AND METHODS: Lymphocyte subsets were quantitated monthly for four healthy individuals from 1986 through 1992 as part of a flow cytometry quality-control program. RESULTS: In general, there were no significant seasonal changes in the total number of white cells or in total lymphocyte counts. The absolute numbers of CD4+ T-lymphocytes were lowest in summer when the CD8+ T-lymphocytes were highest. Mean CD4+ T-lymphocyte counts were 846, 967, 618, and 695 per microL for Subjects 1 through 4, respectively, in winter and 432, 670, 355, and 766 per microL, respectively, in summer. Two healthy subjects had CD4+ T-lymphocyte counts lower than 300 per microL on one or more occasions during the study period. In three of the four subjects, the percentage of B-lymphocytes in winter was almost double that in summer. In one of the four subjects, no circannual rhythm was observed in these lymphocyte subpopulations. CONCLUSION: The seasonal variation in CD4+ T-lymphocyte counts demonstrated in three healthy individuals over almost 7 years is again of interest in light of renewed consideration of using surrogate tests, such as CD4+ T-lymphocyte counts, to screen for AIDS-like diseases that may be in the blood supply.

Adult↗

Modeling the relationship between survival and CD4 lymphocytes in patients with AIDS and AIDS-related complex.

CD4 lymphocyte and survival data from two completed trials, a double-blind placebo-controlled trial of zidovudine in patients with advanced human immunodeficiency virus type 1 (HIV) disease (BW-02 study) and a randomized trial of two different doses of zidovudine in patients with advanced HIV disease (ACTG-002 study) were used to determine the degree to which CD4 lymphocyte counts reflect zidovudine-associated survival benefit. Proportional hazards models were used, and CD4 lymphocyte counts were smoothed by using empirical Bayes estimates. The geometric mean of the CD4 lymphocyte counts increased by 71 and 46 cells/mm3 for patients in the BW-02 and ACTG-002 studies, respectively, followed by a progressive decline. Higher pretreatment CD4 lymphocyte counts (p = 0.001), greater increases in CD4 lymphocytes at 8 weeks (p = 0.1), and smaller declines in the slope (p = 0.001) were associated with a lower risk of death. The most current CD4 lymphocyte count was most prognostic of death (p = 0.001). The risk of death was greater for patients with lower CD4 lymphocytes and this risk increased sharply when the CD4 lymphocyte counts fell below 50 cells/mm3. The hazard of death was higher for placebo recipients at all levels of CD4 lymphocytes compared with zidovudine recipients. Although higher CD4 lymphocyte counts are associated with improved survival, these increases account for only a small proportion of the survival benefit of zidovudine in these two studies.

AIDS-Related Complex↗

Effectiveness of antiretroviral therapy among HIV-infected prisoners: reincarceration and the lack of sustained benefit after release to the community.

Responses to highly active antiretroviral therapy (HAART) in correctional settings and their sustained benefit in prisoners after release are currently not known. To examine the human immunodeficiency virus type 1 (HIV-1) RNA level (VL) and CD4 lymphocyte response to HAART during incarceration and upon reentry to the correctional system, we conducted a retrospective cohort study of longitudinally linked demographic, pharmacy, and laboratory data from the Connecticut prison system. During incarceration, the mean CD4 lymphocyte count increased by 74 lymphocytes/ mu L, and the mean VL decreased by 0.93 log10 copies/mL (P<.0001). Fifty-nine percent of the subjects achieved a VL of <400 copies/mL at the end of each incarceration period. For the 27% of subjects who were reincarcerated, the mean CD4 lymphocyte count decreased by 80 lymphocytes/ mu L, and the mean VL increased by 1.14 log10 (P<.0001). Although HAART use resulted in impressive VL and CD4 lymphocyte outcomes during the period of incarceration, recidivism to prison was high and was associated with a poor outcome. More effective community-release programs are needed for incarcerated patients with HIV disease.

Antiretroviral Therapy, Highly Active↗

Influence of graded magnesium deficiencies on white blood cell counts and lymphocyte subpopulations in rats.

Increased white blood cell counts or leukocytosis have been observed primarily in young rats fed diets extremely low in Mg (< 60 ppm) and high in phosphorus (0.5 % P). We investigated the influence that acute and moderate Mg deficiencies have on blood leukocytes at high and low dietary phosphorus levels. For four weeks, male Sprague-Dawley rats (initially 7 weeks old) were fed diets containing 30, 60, 120, 208, or 850 ppm Mg and either 0.3 % or 0.5 % dietary phosphorus. Total leukocytes were increased in rats fed 30 ppm Mg (p < 0.0001), and the leukocyte subpopulation counts of lymphocytes, neutrophils, monocytes and eosinophils increased significantly only in the rats fed 30 ppm Mg (p < 0.0001). B-cells decreased significantly as a percentage of lymphocytes (p < 0.0093) as dietary Mg decreased. As total counts in blood, B-cells, CD4 and CD8 cells were significantly increased in the rats consuming the 30 ppm Mg diet. Dietary phosphorus only had an effect in combination with the lowest dietary Mg. These results demonstrate a threshold effect for increased leukocytes during a Mg deficiency of four weeks. A Mg deficiency of a longer duration may show different results.

Animals↗

A longitudinal study of leucocyte blood counts and lymphocyte responses in pregnancy: a marked early increase of monocyte-lymphocyte ratio.

Seventy-seven pregnant women were studied repeatedly from the first trimester until 4 weeks after delivery. Neutrophil count was increased but constant in all stages of pregnancy. In contrast, there was a marked increase in monocyte numbers in the first and early second trimester, followed by a gradual decrease towards normal before term. A progressive decrease in total lymphocyte count was observed up to 25-28 weeks, when it increased again, although not reaching the non-pregnant level before term. These fluctuations in monocyte and lymphocyte numbers have not been described before and could explain contradictory findings of previous studies. They may also be important in relation to the mechanisms which prevent rejection of the fetal allograft. Absolute T cell counts were not significantly decreased, but a striking reduction was observed in B cell numbers in early pregnancy. Lymphocyte response to T cell mitogens was decreased throughout pregnancy. It is concluded that immunological studies of pregnancy must take account of the dynamic nature of this condition.

B-Lymphocytes↗