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Use of the Markov model to estimate the waiting times in a modified WHO staging system for HIV infection.

Seroconverting men in the Vancouver Lymphadenopathy--Acquired Immune Deficiency Syndrome Study cohort were studied in this analysis to estimate the waiting times in the different stages of the modified World Health Organization (WHO) staging system for human immunodeficiency virus infection. A time-homogeneous staged Markov model was used, and it was assumed that infected individuals progress irreversibly from Stages I to IV and eventually to death. There were 130 individuals who seroconverted during the study (seroincident) and were included in this analysis. With use of the modified WHO staging system, the estimated mean waiting times for progression to Stage IV were 9.5, 6.5, and 2.0 years from stages I, II, and III, respectively. The estimated survival times were 11.2, 8.2, 3.7, and 1.7 years from Stages I to IV, respectively. Waiting times and survival were not significantly different when the lymphocyte count was used instead of the CD4 cell count in application of the staging system. The application of a staged Markov model to the modified WHO staging system suggests that this is a clinically sensible model. Furthermore, our results confirm that in the absence of CD4 cell counts, lymphocyte counts can be used as an alternative without substantial loss of information.

Adult↗

Re-evaluation of immunological parameters in immunotherapy for advanced carcinoma of the digestive tract.

Fifty-one patients with recurrent carcinoma of the digestive tract received immunotherapy consisting of the streptococcal preparation OK-432 in combination with FT207. In these patients, the following tests were carried out, peripheral blood leukocyte count, lymphocyte count and percent T-cell population of lymphocytes, delayed hypersensitivity skin tests with PPD, phytohemagglutinin and polysaccharide extracted from Su strain of Streptococcus pyogenes and serum titer of agglutinin to Strep. pyogenes. The results were statistically analyzed and correlated with the rate and duration of survival in order to re-evaluate the immunological parameters commonly used at present in anticancer immunotherapy. With respect to the peripheral blood leukocyte count, lymphocyte count, delayed hypersensitivity skin tests and serum titer of agglutinin to Strep. pyogenes assessed at 2 months of treatment, patients showing normal values or positive results had a significantly greater survival rate compared with those showing abnormal values or negative results. The peripheral blood lymphocyte count, delayed hypersensitivity skin tests and serum titer of agglutinin to Strep. pyogenes correlated significantly with survival. Particularly, the Su-PS skin test and serum titer of agglutinin to Strep. pyogenes showed remarkable correlation (P less than 0.01) with the survival rate and period.

Adult↗

Effect of methotrexate on the immune response in children with acute lymphatic leukaemia.

Lymphocyte count, lymphocyte subpopulations identified by monoclonal antibodies and mitogen stimulation assays with phytohaemagglutinin, concanavalin A, pokeweed mitogen and staphylococcal protein A, were used to quantitate the effect of methotrexate on the immune response in children with acute lymphatic leukaemia on maintenance therapy. Methotrexate exerted a profound but apparently short-term effect on these parameters as it is prescribed in current maintenance schedules for childhood acute lymphatic leukaemia. A significant drop in lymphocyte count, affecting all subpopulations, was observed 4 h after oral or intramuscular administration of methotrexate which had reverted to pre-methotrexate values one week after the drug was given. Lymphocyte function was markedly affected, with a major decrease in mitogen responsiveness 1 h after methotrexate and a reversion to pre-methotrexate values by 48 h. A selectivity of suppressor T cells to methotrexate is proposed as being responsible for early recovery. Scheduling of methotrexate in current maintenance programmes would therefore appear to allow adequate time for recovery of immunoresponsiveness between doses.

Age Factors↗

Melatonin and differential effect of L-thyroxine on immune system of Indian tropical bird Perdicula asiatica.

Interaction of thyroxine and melatonin on immune status was noted in vivo and in vitro when peripheral melatonin was high and thyroxine low in plasma of male Perdicula asiatica during reproductively inactive phase. During this phase exogenous thyroxine (4 microg/100g. Bwt./day) and melatonin (25 microg/100g. Bwt./day) increased immune parameters (spleen weight, total leukocyte count, lymphocyte count, percent stimulation ratio) and increased splenocyte density in spleen. In vitro l-thyroxine (10(-6)M/ml) supplementation decreased the splenocyte proliferation which was reversed by melatonin (500 pg/ml) supplementation. In vivo l-thyroxine showed immunoenhancing effect while in vitro it decreased the splenocyte proliferation presenting a differential effect. In the absence of internal physiological conditions of the birds, T(4) showed a negative effect on splenocytes proliferation in vitro when treated alone. However, melatonin maintained its lymphoproliferative effect under both conditions. Thus, avian splenocyte exposed to different hormonal conditions in vitro might have produced different signal peptides other than in vivo, thereby making the result different.

Animals↗

A multiparametric observation of immune competence in breast cancer and its correlation with tumour load and prognosis.

A multiparametric observation of cellular immune status by delayed hypersensitivity response to primary and recall antigens, absolute lymphocyte counts, T-cells counts, lymphocyte stimulation to PHA and serum immunoglobulin levels (IgG, IgM, IgA) was done in 60 patients of breast cancer and 40 age-matched normal controls. The findings were correlated with clinical stage, tumour size, lymphnode involvement, distant metastases, tumour differentiation, lymphoreticular response and tumour recurrence within one year of follow-up period. Delayed hypersensitivity response to DNCB, PPD and Candida was significantly impaired (P = less than .001) in breast cancer patients as compared to normal controls. DNCB and candida response showed a gradual decrease with increasing clinical stage and PPD response was impaired in the advanced stage (Stage III and IV). Patients with well-differentiated tumour were more anergic than those with poorly differentiated tumour. Delayed hypersensitivity response to both primary and recall antigen showed a good correlation with tumour recurrence. Patients who had early recurrence or progressive disease were more anergic to all the three antigens. Absolute lymphocyte counts, absolute T-cells and E-rosette were significantly reduced in breast cancer patients as compared to normal controls and further correlated with clinical stage. Absolute T-cells and E-rosettes were lower in patients with lymphnode involvement, and distant metastases as compared to those with localized tumour. Absence of lymphoreticular response was related with impaired T-cell population. Absolute T-cell counts and E-rosettes further correlated with prognosis of the patients being significantly impaired in patients with early recurrence or with progressive disease (P = less than .05).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

How does neonatal thymectomy affect the immune system?

BACKGROUND: The aim of this study was to determine the effects of neonatal thymectomy on the immune system in later life. METHODS AND RESULTS: Immune system tests were performed in 26 children at 1 year of age. Thirteen of them had been operated for transposition of the great arteries and had thymectomy in the same operation in the neonatal period. Thirteen control subjects were normal. Immune system tests including white blood cell count, lymphocyte count, T and B cells subgroups (CD2, CD4, CD5, CD7, CD8, CD16, CD20, CD22, CD56), mitotic reaction to phytohaemagglutinin in lymphocyte culture. White blood cell count and lymphocyte count were performed. In the statistical analysis, Mann-Whitney U and Wilcoxon rank sum W tests were used for both groups. Statistical significance was taken at a value of P < 0.05. There was no significant difference in mean white blood cell count, mean blastic transformation reaction of lymphocytes to phytohaemagglutinin, and CD7, CD4/CD8, CD20, CD22, CD56 ratios between the two groups (P > 0.05). Significant differences in mean lymphocyte number, and CD2, CD4, CD5, CD8, CD16 ratios between the two groups were defined (P < 0.05). CONCLUSIONS: In our study, it was noticed that mainly T lymphocyte subgroups were effected by neonatal thymectomy. Although no infection requiring therapy was seen in the thymectomized patients, we advise to limit total thymectomy as much as possible in neonatal heart operations.

Case-Control Studies↗

Serial changes in cellular immunity of septic patients with multiple organ-system failure.

Total lymphocyte count, lymphocyte cell-surface markers (OKT3, OKT4, OKT8, and B-1), serum complement factors (C3 and C4), immunoglobulins (IgG, IgA, and IgM), ceruloplasmin (Crl), and transferrin (Trf) were determined weekly for nine septic postoperative patients, all of whom had multiple organ-system failure. The peripheral blood total lymphocyte count, its subpopulation, T-cell subset, and proliferative responses of lymphocyte to phytohemagglutinin (PHA) and concanavalin A (Con A) decreased in all patients. OKT3 and B-1 decreased progressively in the four nonsurvivors compared with the five survivors. Although immunoglobulin levels were within the normal range in both groups, they tended to increase in survivors and decrease in nonsurvivors. Serial levels of C3, C4, Crl, and Trf increased in survivors but did not change in nonsurvivors. T-cell function and antibody-producing activity diminished progressively in nonsurvivors. These changes in cellular immunity may represent another manifestation of multiple organ-system failure during sepsis.

Adult↗

Activity of serum thymidine kinase in non-Hodgkin lymphoma: relationship to other prognostic factors.

The value of serum deoxythymidine kinase (TK) for the staging and evaluation of disease activity of non-Hodgkin lymphoma (NHL) as compared with serum beta 2-microglobulin, serum lactate dehydrogenase, blood sedimentation rate, blood hemoglobin, white blood cell count, lymphocyte count and platelet count was investigated in 101 patients. In addition, the performance status was determined by the Karnofsky index. Patients with chronic lymphocytic leukemia (CLL; n = 43) and immunocytoma (IC; n = 19) were staged according to the Binet classification, and the other low (n = 28) and high grade NHL (n = 8) according to the Ann Arbor classification. The analysis of all CLL and IC patients revealed that TK values correlated better with Binet stages (p = 0.01; n = 58) than blood sedimentation rate (p = 0.05, n = 12), lactate dehydrogenase (p = 0.08; n = 50), beta 2-microglobulin (p = 0.29; n = 28), lymphocyte count (p = 0.70; n = 57), white blood cell count (p = 0.69, n = 59) and the Karnofsky index (p = 0.16, n = 50). Mean TK levels of these patients were for Binet stage A 6.2 +/- 0.8 U/l (mean +/- S.E.M., range 2.3-18.0), stage B 13.3 +/- 6.5 U/l (3.8-38.8) and stage C 19.6 +/- 4.4 U/l (1.9-79.0), and for 22 healthy controls 3.8 +/- 0.2 U/l (2.2-6.0). Patients with multiple courses of chemotherapy (n = 32) previous to the study had significantly (p = 0.01) higher TK levels (16.4 +/- 3.7 U/l; 2.3-79.0) than those with only up to one course (n = 66; TK: 8.6 +/- 1.4 U/l; 1.5-66.3). The follow-up of 16 patients with low grade NHL showed that serum TK levels paralleled well the clinical response. The results indicate that TK might be a worthful parameter to estimate progression and response to therapy of NHL.

Adult↗

Hematologic and serum biochemical values in aged female bonnet macaques (Macaca radiata) anesthetized with ketamine hydrochloride.

We investigated the effect of ketamine hydrochloride anesthesia on hematologic and serum biochemical values in 10 aged female bonnet macaques (Macaca radiata) before and 120 min after intramuscular administration of ketamine hydrochloride (15 mg/kg body weight). Ketamine anesthesia caused significant reduction in the total leukocyte count, lymphocyte count, red blood cell count, hemoglobin concentration, packed cell volume, and serum concentrations of glucose, total protein, alkaline phosphatase, calcium, sodium, and potassium. Although the effects of ketamine hydrochloride on hematologic and serum biochemical values have been reported for most of the nonhuman primates, no literature on bonnet macaques is available. These findings will be useful in designing experiments assessing pathologic and toxicologic changes in blood and serum parameters and interpreting data obtained from aged bonnet monkeys.

Aging↗

[Acute cholecystitis: video-laparoscopic or laparotomic treatment? Role of the immune system].

Recent clinical studies suggest that laparoscopic cholecystectomy (LC) causes less depression of cell-mediated immunity than open cholecystectomy. LC is a so called "mini invasive" surgical presidia, and on the basis of this consideration we have investigated if and how the immune response is modified in patients with acute cholecystitis after laparoscopic cholecystectomy compare to patients undergone open cholecystectomy. Immune-activity (neutrophils, total lymphocytes count, lymphocytes subpopulations, HLA-DR, 6-Interleukin, skin multitests) was evaluated in 28 patients 24-36 hours before surgery and p.o. after 1, 3 and 6 days: 16 patients underwent "open" cholecystectomy and 12 LC. One day after surgery patients with open cholecystectomy showed significant increase (p < or = 0.05) of plasma neutrophils and 6-Interleukin, while these parameters were almost unchanged in patients with LC. Moreover, skin tests showed ipo or anergic response in the majority (81.8%) of patients with "open" surgery compare to patients with LC (10.5%): (p < or = 0.05). Finally monocyte antigen HLA-DR was also reduced in patients with "open" cholecystectomy: in this group we also recorded 2 cases (12.5%) of respiratory tract infection. In conclusion, LC for acute cholecystitis, avoids p.o. immunosuppression with better p.o. morbidity compare to open surgery.

Acute Disease↗

Prediction of cytomegalovirus pneumonia after marrow transplantation from cellular characteristics and cytomegalovirus culture of bronchoalveolar lavage fluid.

Bronchoalveolar lavage (BAL) was performed between days 35 and 45 posttransplant in 37 marrow recipients without clinical or radiologic evidence of cytomegalovirus (CMV) pneumonia to determine if the presence of CMV or cellular characteristics was predictive of subsequent development of CMV pneumonia. Analysis of BAL fluid included culture and direct fluorescent antibody staining for CMV, total mononuclear cell count, lymphocyte count, and lymphocyte subsets. Patients were followed to day 110 after transplant for development of CMV pneumonia. Weekly cultures of blood, urine, and throat were also obtained. BAL was positive for CMV in 7 patients, of whom 3 developed CMV pneumonia. It was negative for CMV in 30 patients, of whom 7 developed CMV pneumonia. The positive and negative predictive values for detection of CMV in day 35-45 BAL were 43% and 78%, for CMV viremia 66% and 87%, and for detection of CMV in urine and throat 41% and 94%, respectively, for subsequent CMV pneumonia. In 9/10 patients who subsequently developed CMV pneumonia, excretion of CMV from BAL, blood, urine or throat preceded CMV pneumonia, and BAL was the earliest site of CMV excretion in all nine. Only one patient did not excrete before developing CMV pneumonia. In a stepwise logistic regression of risk factors for developing CMV pneumonia, only CMV viremia was significant (P = 0.002) although the total BAL mononuclear cell count approached significance (P = 0.053). The percentage of lymphocytes in BAL and CMV excretion in BAL, urine, and throat were not significant. The positive predictive value of BAL for subsequent CMV pneumonia was no greater than that of culture of urine and throat and less than that of viremia in our patients.

Adult↗

Normoblasts in large for gestational age infants.

Thirty one term large for gestational age (LGA) infants of non-diabetic mothers were compared with 30 appropriate for gestational age controls. Median absolute nucleated red blood cell counts, lymphocyte counts, and packed cell volumes were significantly higher in the LGA infants than the controls. It is possible that LGA babies of non-diabetic mothers are exposed to relative intrauterine hypoxia.

Case-Control Studies↗

[Studies on the classification of clinical stage and histopathological grade of gastric cancer, the contribution of clinical findings and clinico-pathological changes including immunological responses].

The data from 329 gastric cancer patients (206 males and 123 females) were applied to the following statistical analysis. The stage of gastric cancer progress, which was determined by the general rules for the gastric cancer study in Japan, the counterpart of the TNM classification was predictable by a multi-variative mathematical model based on Hayashi's quantification theory which allowed to use qualitative variables as well as quantitative ones for the calculation using the variables relevant to clinical findings consisted of the grade of surgical operability, the grade of histopathological change, positive or negative liver metastasis, positive or negative histopathologically detectable lymph-node metastasis and so on. The variables relevant to clinical findings predicted accurately the stage by the above-cited model and multi-variative correlation coefficient (R2) was 0.9475, suggesting that 95% of the values predicted by those variables could identical to the observed value of the cancer stage. The variables relevant to clinical findings contributed only 29% (R2 = 0.2902) to the prediction of the histopathological grade. The stage and the histopathological grade also were predictable with the multi-variative regressive equations using the data of the clinico-pathological examinations which were administered on the day before the operation to 239 patients (139 males and 95 females) of gastric cancer and 82 control surgical patients (50 males and 32 females). The clinico-pathological indicators consisted of the SI values of Con A and PHA, leukocytes' count, lymphocytes' count, serum albumin concentration, B- and T-cell numbers. The factors which contributed to the stage, or the histopathological grade of gastric cancer were extracted respectively through principal component analysis using the respective correlation matrices consisted of the variables used for the calculation of the multi-variative regression equations in order to predict the stage or histopathological grade. For the male patients, the aging factor contributed to both of the stage and the histopathological grade. For the female patients, the factor relevant to the complication such as infectious diseases and low-nutrition emaciating the patient contributed to the cancer stage and the factor relevant to T-lymphocyte function contributed to the histopathological grade.

Aged↗

The effects of total parenteral nutrition on immunodepression due to malnutrition.

An experimental study was performed in 16 dogs to investigate the effects of sub-acute malnutrition on humoral and cellular immunity and phagocytic functions and, subsequently, to investigate the ability of total parenteral nutrition (TPN) to restore abnormal immunological variables. Deficiencies of IgG, C3, primary immune response to sheep red blood cells (SRBC),lymphocyte counts, lymphocyte response to phytohemagglutinin (PHA), and neutrophi chemotaxis were found to be caused by malnutrition. Nutritional repletion by means of TPN resulted in a return to normal or supranormal serum concentrations of IgG, IgM, and C3, and the primary immune response to SRVC was prompter and higher. Moreover, TPN resulted in restoration of normal neutrophil chemotactic responses. TPN did not improve lymphocyte response to PHA in these experiments. The study demonstrates that subacute malnutrition results in broad based deficiencies of the immunological response of the type that predispose to infection and that the proper use of TPN can correct most of these abnormalities.

Animals↗

[Studies of immunological function in patients with ovarian cancer].

Immunological function in patients with ovarian cancer was studied using parameters including peripheral blood lymphocyte counts, lymphocyte subsets, PHA-induced lymphoproliferative (PHA-LP) reaction, PPD skin test and immunoglobulin levels. The following results were obtained: The number of total lymphocytes, T cells (OKT 11+) and B cells (OKIa 1+) in peripheral blood were found to be decreased in patients with advanced carcinoma. The positive rate of PPD skin test was also lower in the patients. OKT8+ cells were significantly increased in the disseminated carcinoma (DC) group and the OKT4+/OKT8+ ratio in the DC group was markedly decreased when the results were compared with the control and the patients in the localized carcinoma (LC) group. PHA-LP reaction and serum IgM level in the patients in the LC and DC groups were found to be significantly lower than in the control group. The percentage of T cell (OKT11+), serum IgG and IgA levels were not altered in any clinical stage of the patients.

Adenocarcinoma, Mucinous↗

Association of cytomegalovirus infection with increased morbidity is independent of transfusion.

Forty-three consecutive trauma patients with an injury severity score greater than 20 were studied prospectively for evidence of cytomegalovirus (CMV) infection. Twenty-one patients had serologic conversion: 3 with primary CMV infections, 18 with reactivation of CMV infection (CMV group). Twenty-two patients had no serologic conversion (no CMV group). To differentiate the effects of CMV and transfusion, the CMV group and the no CMV group were each divided into high (more than 10 units) and low (less than 10 units) transfusion subgroups. Similar fever peaks, leukocyte counts, lymphocyte counts, and incidence of major bacterial sepsis were recorded for the four subgroups. Several factors were significantly associated with CMV infection independent of transfusion, including increased duration of major bacterial sepsis and number of septic episodes per patient; prolonged duration of anergy; increased duration of intensive care unit and hospital stay; increased duration of ventilatory assistance and rate of tracheostomy; and increased suppressor cells, decreased helper: suppressor ratios, increased functional suppressor cells, and increased natural killer cells. Although mortality was not increased with CMV infection, our data suggest that such infection after trauma may delay recovery from major bacterial infection, often resulting in a major increase in morbidity.

Antibodies, Viral↗

The effect of EHV-1 infection upon circulating leucocyte populations in the natural equine host.

It has been suggested that EHV-1 infection may perturb immune responsiveness in the natural equine host. The mechanism underlying this phenomenon is not clear, but disturbances of circulating leucocyte populations could contribute. In order to objectively assess the nature of the haematological changes provoked by EHV-1 infection, two groups of conventionally-maintained Welsh mountain ponies were challenge-infected intra-nasally with the Ab4 isolate of EHV-1. These groups were controlled by similarly-sized groups of non-infected ponies. All data generated was subjected to rigorous statistical analysis. Whole leucocyte count, neutrophil count, lymphocyte count, pan T cell count (RVC1 + cells-putative CD5 homologue), T cell subset count (RVC3 + cell-putative CD8 homologue), RVC2 + cells (putatively class II MHC+) and B cell count were recorded in experimental and control subjects at frequent intervals post-infection via flow cytometry. The principal abnormalities post-infection were T cell lymphopaenia, neutropaenia and the appearance of blastic cells of undetermined lineage. This study underlined the variability of EHV-1 infection in the natural, outbred equine host.

Animals↗