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Pre-eclampsia--a state of mother-fetus immune imbalance.

Serial lymphocyte counts and function tests were done during and after pre-eclamptic pregnancies, and in the offspring. Compared with normal pregnancies, pre-eclamptic pregnancies were associated with lower B-lymphocyte counts in the fathers; lower T-lymphocyte count, lower B-lymphocyte count, and impaired T-lymphocyte function in mothers; a low response in mixed lymphocyte culture (MLC) tests between the mother and father; and an increased B-cell count in the children. Follow-up of one pre-eclamptic woman throughout pregnancy showed important immune changes at the beginning of the second trimester. These findings suggest that pre-eclampsia is caused by a combination of maternal and paternal hyporesponsiveness together with fetal hyperresponsiveness.

B-Lymphocytes↗

The role of peripheral lymphocytes in the prediction of recurrence in Crohn's disease.

Sixty-five patients with Crohn's disease admitted for surgical treatment to The Mount Sinai Hospital were studied prospectively to determine whether or not preoperative peripheral lymphocyte counts correlate with early recurrence. Twenty-four patients had symptomatic recurrent disease develop within three years after operation. Patients who had recurrences were found to have significantly lower preoperative lymphocyte counts than patients doing well three years after surgical resection. Sixty-nine per cent of the patients with preoperative lymphocyte counts of less than 1,000 cells per cubic millimeter had recurrent disease develop within three years of the operation. In contrast, only 8 per cent of the patients with preoperative lymphocyte counts of more than 2,100 cells per cubic millimeter had recurrences. It appears that patients with marked preoperative lymphocytopenia are more likely to develop early symptomatic recurrences after surgical treatment than patients with normal lymphocyte counts.

Adult↗

Leukocyte counts and lymphocyte responsiveness associated with repeated bouts of strenuous endurance exercise.

This study compared leukocyte counts and lymphocyte responsiveness during and after a second bout of high-intensity endurance exercise on the same day with the response to a similar but single bout of exercise. Nine athletes participated in three 24-h trials: 1) rest in bed (Rest); 2) one bout of exercise (One); and 3) two bouts of exercise (Two). All bouts consisted of 75 min at approximately 75% of maximal O(2) uptake on a cycle ergometer. Lymphocytes in whole blood were stimulated with monoclonal antibodies against CD2 and assessed by flow cytometry for expression of the early activation molecule CD69. The second bout of exercise in the Two trial was associated with significantly increased concentrations of total leukocytes, neutrophils, lymphocytes, CD4(+), CD8(+), and CD56(+) cells and a significantly decreased percentage of CD56(+) cells expressing CD69 compared with a single bout. Additionally, there was a significantly decreased CD69 fluorescence in CD56(+) cells postexercise. These differences suggest a "carry-over" effect in the immune system from a first to a second bout of exercise on the same day.

Adult↗

Cell-mediated immunity to gluten fraction III in adult coeliac disease.

A migration inhibition test was used to assess sensitisation of blood leucocytes, and thus cell-mediated immunity, to gluten fraction III in controls and patients with coeliac disease. Migration indices were significantly less (indicating sensitisation) in untreated and in treated patients than in controls, and significantly less in treated patients than in untreated patients. At a concentration of 1 mg/ml gluten fraction III, 13% of untreated patients and 54% of treated patients had migration indices in the sensitised range. At 2 mg/ml gluten fraction III, sensitisation was demonstrated in 8% of untreated patients and 48% of treated patients. After starting a gluten free diet, migration indices fell into the sensitised range in all patients followed. After at least nine months on a gluten free diet, migration indices were significantly higher in those patients with a normal interepithelial lymphocyte count than in those patients with a raised interepithelial lymphocyte count. Cell-mediated immunity to gluten fraction III can be detected in the peripheral blood of certain patients with coeliac disease. Detectable sensitivity is related to the time on a gluten free diet, and the interepithelial lymphocyte count.

Adult↗

Delayed cutaneous hypersensitivity tests and lymphopenia as activity markers in sarcoidosis.

STUDY OBJECTIVES: To evaluate new and already known biological markers of activity in patients with sarcoidosis. DESIGN: A 10-year prospective clinical evaluation, including a battery of delayed cutaneous hypersensitivity tests (DCHTs) and other markers of activity. SETTING: Outpatient department of a university teaching hospital. PATIENTS: Forty patients with biopsy-proven sarcoidosis were prospectively evaluated every 6 months. In this study, only the visits that fulfilled the situation of active period (AcP) or of asymptomatic period (AsP) were taken into account. Twenty-one visits were considered to be in the AcP, and 26 were considered to be in the AsP. Seven patients were studied both in the AcP and the AsP. INTERVENTIONS: DCHTs and blood sample extraction every 6 months. MEASUREMENTS AND RESULTS: The mean diameter of the cutaneous wheal for each antigen (AG) was lower in the AcP group than in the AsP group (candidine, p < 0.0001; tuberculin, p < 0.0009; trichophytin, p < 0.02; streptokinase-streptodornase, p < 0.001). Also, the mean (+/- SD) diameter for the four AGs taken together was lower in the AcP group (2.3 +/- 4.2 mm) than in the AsP group (16.8 +/- 9.3 mm; p < 0.0001). The mean serum angiotensin-converting enzyme (S-ACE) value was higher in the AcP group than in the AsP group (p < 0.02). A low lymphocyte count and a percentage of the lymphocyte count (< 20%) also were detected more frequently in the AcP group than in the AsP group (p < 0.02 and p < 0.0001, respectively). CONCLUSIONS: DCHTs appear to be a simple, reliable, and easily performed marker of inflammatory activity in sarcoidosis patients. Furthermore, serum total and differential lymphocyte count and the S-ACE level proved to be useful inflammatory markers in this study.

Adult↗

Factors associated with Pneumocystis carinii pneumonia in Wegener's granulomatosis.

OBJECTIVE: To determine the factors associated with the occurrence of Pneumocystis carinii pneumonia (PCP) in Wegener's granulomatosis (WG). METHODS: We retrospectively compared a group of 12 patients with WG and PCP (PCP group), with 32 WG patients without PCP followed over the same period in the same centres (control group). RESULTS: The mean delay of onset of PCP after the start of the immunosuppressive therapy was 127 (SD 128) days. Before treatment, the clinical and biological features of the two groups were similar, except for the mean lymphocyte count which was lower in the PCP group than in the control group (1060/mm3 v 1426/mm3; p = 0.04). During treatment, both groups were lymphopenic. There was a significant difference between the lowest absolute lymphocyte count in each group (244/mm3 in the PCP group v 738/mm3 in the control group; p = 0.001). During the first three months of treatment, the lymphocyte count was less than 600/mm3 at least once in 10 of the 12 patients in the PCP group and in 11 of the 32 patients in the control group (p < 0.01). The mean cumulative dose of cyclophosphamide was greater in the PCP group than in the control group at the end of both the second (1.55 mg/kg/day v 0.99 mg/kg/day; p = 0.05) and the third (1.67 mg/kg/day v 0.97 mg/kg/day; p = 0.03) months. However, in multivariate analysis, the only two factors independently and significantly associated with the occurrence of PCP were the pretreatment lymphocyte count (p = 0.018) and the lymphocyte count three months after the start of the immunosuppressive treatment (p = 0.014). CONCLUSIONS: The severity of lymphocytopenia before and during immunosuppressive treatment is the factor best associated with PCP in WG.

Female↗

Hematologic dysfunction in Lassa fever.

Lassa fever is widespread in West Africa, where the case fatality is about 16% in hospitalized adult patients. The clinical course is highly variable, with a few patients developing severe disease with bleeding, adult respiratory distress syndrome, encephalopathy and hypovolemic shock. We studied 70 patients admitted with suspected Lassa fever to a hospital in Sierra Leone, West Africa. Fourteen patients classified as having severe Lassa fever on the basis of serum aspartate amino transferase (AST) greater than 150 IU/L or viremia of greater than 10(3.6) tissue culture infective dose (TCID) 50/ml were found to have statistically significantly depressed lymphocyte counts when compared with patients with mild Lassa fever (AST less than 150 IU/L or viremia, less than 10(3.6)TCID50/ml), (P less than 0.0001) and with febrile control patients, in whom Lassa infection had been excluded by laboratory criteria (P less than 0.0008). Maximum depression occurred a mean of 10.9 days post onset. Patients with severe Lassa fever also had moderate thrombocytopenia, which was statistically significant when compared with febrile control patients (P less than 0.0003) and this occurred a mean of 10.8 days postonset. The most significant changes were in platelet function, which was markedly depressed in patients with severe Lassa fever (P less than 0.0035 in response to ADP and P = 0.0081 for collagen) when compared with patients with mild Lassa fever, and when compared with febrile controls, (P = 0.0013 for ADP and P less than 0.00001 for collagen). This abnormality was usually maximal on admission to hospital, and probably is an early event, preceding hospitalization in these patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Humans↗

[Evolution of CD4 and CD8 lymphocyte subsets in HIV seronegative and seropositive hemophiliacs].

PURPOSE: To asses the evolution over time of the CD4, CD8 and total lymphocyte counts in both HIV seronegative and HIV seropositive haemophiliacs. PATIENTS AND METHODS: A total of 124 haemophilic patients (77 HIV seropositive and 47 HIV seronegative) regularly controlled at our Hospital were studied. All patients have had several (range 2-15) CD4 and CD8 lymphocyte counts, with a minimum interval of 2 or more years between the first count and the last one (median 7.7 years). A linear regression analysis of the serial cell counts against the time was made and the corresponding slopes were estimated for each patient and expressed as a percentage of the initial values (standardized slopes). RESULTS: In HIV seronegative patients the number of CD4, CD8 and total lymphocytes decreased (p < 0.05), but the decrease of the CD4/CD8 ratio was not statistically significant. The decline of the CD4 cells showed a trend to remain above 500 cells/microL. HIV seropositive hemophiliacs had also a substantial decline of lymphocyte counts (p < 0.0001), but essentially due to changes of the CD4 cells, which declined with a nearly constant rate during the follow-up (median values decreased from 793/microL to 324/microL). CD8 cell counts diminished in lower grade than the CD4 cells counts, and consequently the percentage of the total lymphocyte number increased from 42% to 55%. The CD4/CD8 ratio decreased with a standardized slope of -5.7% per year. At the initial evaluation the seropositive patients had CD4 cell counts and CD4/CD8 ratios lower than seronegative ones, but CD8 cell counts were higher in the first group. Total lymphocyte counts were not statistically different at this first evaluation between infected and non-infected patients. At the final evaluation, differences on CD4 cell counts and CD4/CD8 ratio increased, and lymphocyte counts were significantly lower in the HIV-seropositive haemophiliacs. However, the final absolute counts of CD8 cells were not dissimilar in the two groups of patients. The median standardized slopes of the total lymphocyte counts, CD4 cell counts, and CD4/CD8 ratios were significantly more negative for the HIV-infected patients (-5.7%, -9.4 and -5.7%, respectively) than were these for the non-infected ones (-2.0%, -3.2% and -2.5%, respectively). CONCLUSIONS: Lymphocyte counts, mainly the CD4 cell counts, decline in treated haemophiliacs independently of their HIV status. In the HIV seronegative patients the CD4 cell counts generally stabilize above 500 cells/microL. However, in the seropositive haemophiliacs these counts show a continuous fall, with a median rate of 9% of the initial value per year.

Adolescent↗

HIV-HCV RNA loads and liver failure in coinfected patients with coagulopathy.

BACKGROUND AND OBJECTIVE: The aim of this study was to measure contemporaneously HCV-RNA load, HIV-RNA load and CD4+ lymphocyte count in HCV/HIV coinfected patients with coagulopathy and to examine the relationship between these parameters and the liver failure. DESIGN AND METHODS: A cross-sectional study was performed on 54 patients with severe coagulopathy: 39 HCV/HIV coinfected and 15 HCV+/HIV- comparable for age and HCV exposure time. HCV-RNA and HIV-RNA load, CD4+ lymphocyte count, biochemical and ultrasonographic parameters were evaluated at the time of entry to the study. RESULTS: Mean HCV-RNA load was significantly higher in coinfected patients (643,872 717,687 copies/mL) than in HCV+/HIV- (mean 161,573 276,896 copies/mL) (p = 0.01). The 39 HCV/HIV coinfected patients had a mean HIV-RNA load of 205,913 456,311 copies/mL (range 4,000-2,500,000) and a mean CD4+ lymphocyte count of 206.5171/microL (range 5-693). Five of the 39 (12.8%) coinfected patients had liver failure. In these five patients the mean HCV-RNA load (770,200 996,426 copies/mL) was high but not significantly different from that in the 34 HCV+/HIV+ patients (623,496 682,239 copies/mL) without liver failure (p = 1.0). Coinfected patients with liver failure had a significantly higher HIV-RNA load (mean 764, 599 978,542 copies/mL) and lower CD4+ lymphocyte count (mean 52.655. 6/microL) than those observed in coinfected patients without liver failure (p = 0.007 and p = 0.03, respectively). A significant inverse correlation was found between CD4+ lymphocyte count and HIV-RNA load (r = -0.37, p = 0.01). INTERPRETATION AND CONCLUSIONS: HCV-RNA load is significantly higher in HIV+ than in HIV- patients with coagulopathy. Liver failure was found only in the HCV/HIV coinfected patients with severe immunodepression, expressed either by low CD4+ lymphocyte count or by high HIV-RNA load.

Adult↗

A proposal for basic management of HIV disease in west Africa: use of clinical staging and haemogram data.

Our objective was to propose a strategy to screen HIV-infected African people for biological immunodeficiency easily. In a cross-sectional study, we analysed the patterns of diseases and of CD4 counts among 266 HIV-infected adults. Peripheral facial paralysis and chronic cutaneo-mucous diseases were the earlier B-stage diseases. Pulmonary tuberculosis was close to B-stage diseases, and chronic diarrhoea was borderline between B and C stages. Cachexia was the most frequent C-stage symptom (47.8%). Ninety per cent of CDC-C stage people had CD4 counts below 350/microliter, whereas only 75% had CD4 counts below 200/microliter. Regression analysis identified the lymphocyte count, clinical stage and platelet count as predictors of CD4 count below 350/microliter. A simple score (lymphocyte count < or = 2500/microliter and clinical stage > or = B) is proposed to determine this CD4 threshold (positive predictive value: 83%) and to determine those patients needing treatment to prevent wasting and opportunistic infections.

AIDS-Related Opportunistic Infections↗

[Basic studies on oral administration of lentinan (I)--influence on lymphocyte subsets in peripheral venous blood].

The effect of oral administration of lentinan (LTN), a biological response modifier, in the control of systemic immune function was studied in 6-week old male Wistar-Imamichi SPF rats. In the LTN group, 1 mg LTN dissolved in 1 ml physiological saline was administration forcibly into the stomach twice weekly. Physiological saline alone was administered in a similar fashion to the control group. Blood samples were obtained prior to and after four and eight weeks of administration. White blood cells and lymphocyte counts were obtained and lymphocyte subsets were measured using monoclonal antibodies W3/13, W3/25 and 0 X 8 (Sera-Lab), and a laser flow cytometry system (Orthospectrum III, Orthodiagnostic System). The T cell ratio, helper/inducer T (Th) cell ratio, and suppressor/cytotoxic T (Ts) cell ratio were measured. The peripheral white blood cell count and lymphocyte count were not significantly different between the control and LTN groups. After four weeks of LTN administration, however, the LTN group showed a significantly higher T cell ratio, Th cell ratio and Th/Ts cell ratio than did the control group, and the Ts cell ratio was significantly lower. In the groups undergoing administration for eight weeks, no difference was noted in the lymphocyte subsets between the two groups. Oral administration of LTN apparently modulates the systemic immune function through T cell stimulation, especially Th cells, but continued administration may induce a tolerance to the effect of LTN.

Administration, Oral↗

Early lymphocyte recovery as a prognostic indicator for high-risk Ewing sarcoma.

BACKGROUND: Increasing evidence suggests that lymphocyte recovery plays a major part in tumor control. Facilitating immune reconstitution might be a novel direction of cancer therapy. The purpose of this study was to determine if early lymphocyte recovery is an independent prognostic indicator for high-risk Ewing sarcoma outcome. RESULTS: Data of 24 Ewing sarcoma patients were analyzed (age, 3 to 50 y; median, 16.5; male to female, 16:8). The 5-year overall survival (OS) of the total population was 47.9% [10.6 standard error (SE)]. Patients were separated into 2 groups: prolonged lymphopenia versus early lymphocyte recovery, using a threshold absolute lymphocyte count (ALC) of > or =500 cells/microL on day 15. The majority (67%; n=16) of the patients had an ALC > or =500 cells/microL, and of these 10/16 are alive with a 5-year OS of 58.7% (13.2 SE). In contrast, 33% (n=8) of patients had an ALC <500 cells/microL on day 15 and only 2/8 are alive with a 5-year OS of 25% (15.3 SE). This difference was significant (P=0.007 using the log rank test). When comparing patients with metastatic disease, patients with an ALC-15 < 500 cells/microL had a median survival of 13 months, whereas patients with an ALC-15 > or =500 cells/microL had a median survival of 29.5 months. All patients had an ALC before chemotherapy of >1000 cells/microL. The difference was significant (P value=0.001 using the log rank test). Univariate analysis of platelet counts, age, sex, and absolute neutrophil count showed no statistically significant association with OS. CONCLUSIONS: The data demonstrate that an ALC > or =500 cells/microL on day 15 of the first course of chemotherapy is an independent prognostic factor associated with superior OS in high-risk Ewing sarcoma.

Adolescent↗

Effect of three months treatment with Ukrain on peripheral blood morphology in rodents.

Studies on Albino Swiss mice and Wistar rats have demonstrated that Ukrain administered intraperitoneally (i.p.) for three months produces the following effects in the haematologic parameters: increased leucocytes and decreased thrombocytes. The haemoglobin and erythrocyte levels, as well as haematocrit value, were unchanged. In the leucogram changes were observed; i.e., a fall in the number of neutrophil segments and an increase in the lymphocyte count. The erythrocyte indices, P.C.V., M.C.V., M.C.H. and M.C.H.C. were not changed by a period of three months i.p. Ukrain administration. The observed changes were more marked in female than in male animals and were greater in mice than in rats.

Alkaloids↗

[Serum levels of soluble tumor necrosis factor receptors as markers for disease progression of human immunodeficiency virus infection].

We studied whether the serum levels of soluble tumor necrosis factor receptor(sTNFR) type I or II correlate with clinical progression of human immunodeficiency virus type 1(HIV-1) infection. Serum levels of sTNFR type I and II were measured by an enzyme-linked immunosorbent assay in sixty five patients with HIV-1 infected hemophiliacs and 10 healthy controls. In a longitudinal study, we assessed whether the decline of CD4+ lymphocyte counts were associated with increased serum concentrations of sTNFRs. Elevated serum concentrations of sTNFRs were found among the HIV-1 infected patients and higher in patients with advanced clinical stage. We noticed there were two distinct patient groups in change of CD4+ lymphocyte count when twenty-eight patients were followed retrospectively for a median period of 65 months. 14 patients represented stable CD4+ lymphocyte counts, but another 14 patients had more than 40% decrease of CD4+ lymphocyte counts over the course of this study. Serum sTNFR type II levels were 3.49 +/- 0.71 to 3.11 +/- 0.31 ng/ml in the former group, and 4.88 +/- 0.91 to 4.26 +/- 0.71 ng/ml in the latter group during the study. Significantly higher levels of sTNFR type II were already revealed at early time in the latter group. There was, however, no significant difference in the level of sTNFR type I between the two. These results suggest that serum levels of sTNFR type II provided useful information as a predictor of disease progression related to the decline of CD4+ lymphocyte counts.

Adult↗

Plasma and lymphocyte cyclic nucleotide response to acute exercise in healthy adults.

Plasma and lymphocytic cyclic nucleotide levels were assayed in 11 (5 male, 6 female) healthy normal adults before and after bicycle ergometry exercise. Lymphocytosis after exercise was observed. Plasma cAMP level was increased by almost 2 fold after exercise. However, plasma cGMP level was not affected. On the contrary, lymphocytic cAMP level was decreased by one third while cGMP level was halved. There were linear regression relationships between maximum heart rate and % difference in lymphocyte count and lymphocytic cyclic nucleotide levels pre- and post-exercise. Our findings demonstrate that higher cardiac output leads to increased lymphocytosis but decreased lymphocytic cyclic nucleotide levels.

Adenosine Monophosphate↗

Hematologic and serum biochemical variables and plasma corticotropin concentration in healthy aged horses.

OBJECTIVES: To compare hematologic and serum biochemical variables and plasma ACTH concentration between healthy horses 5 to 12 years old and those more than 20 years old. ANIMALS: 30 healthy horses 5 to 12 years old and 30 healthy horses more than 20 years old. PROCEDURES: Venous blood was collected from all horses, and CBC and serum biochemical analysis were performed for each horse. Plasma ACTH concentration was determined by radioimmunoassay. Student's paired t-test or the Mann-Whitney rank sum test was used to compare values between control and aged horse groups. RESULTS: Compared with values for control horses, aged horses had significantly higher erythrocyte mean cell volume and mean cell hemoglobin. Aged horses also had significantly decreased total lymphocyte count. Five aged horses had lymphocyte count that was lower than the low reference limit as established for horses in our laboratory. Differences between control and aged horses for serum biochemical or plasma ACTH values were not significant. CONCLUSION: Compared with younger adult horses, those more than 20 years old have some hematologic differences, but there is no apparent effect of aging on baseline plasma ACTH concentration. CLINICAL RELEVANCE: It is important to establish age-matched control values for optimal interpretation of clinicopathologic variables.

Adrenocorticotropic Hormone↗