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[A study of the correlation between the stromal reaction to the primary lesion and immunological parameters in patients with cervical cancer (author's transl)].

A correlation between the stromal reaction to the primary lesion and the clinical immunoparameters, such as, the depth of primary lesion, regional lymph node metastasis, delayed hypersensitivity reactions (DNCB, PPD and PHA skin reaction), peripheral lymphocyte count, peripheral monocyte count, peripheral lymphocyte blastogenesis to PHA and prognosis were studied in patients with cervical cancer (stage Ib, II). All patients were treated with curative operation. The degree of stromal reaction was classified to 3 groups, that is, marked stromal reaction group, moderate stromal reaction group and slight stromal reaction group and the following results were obtained. 1) There was a significant correlation between the degree of stromal reaction and the depth of primary lesion, regional lymph node metastasis (p less than 0.05). 2) The degree of stromal reaction was correlated with the positive rate of DNCB skin reaction (p less than 0.05), but there was no significant correlation between the degree of stromal reaction and the positive rate of PPD and PHA skin reaction. 3) The degree of stromal reaction was not correlated with the count of peripheral lymphocyte, monocyte and the ability of lymphocyte blastoid transformation. 4) The recurrence rate in marked stromal reaction group was 13.6%; 22.2% in moderate group and 28. 6% in slight group. There was no significant correlation in the group. 5) Five-years-survival rate in marked stromal reaction group ws 86.4%; 81.5% in moderate group and 71.4% in slight group. There was also no significant correlation in the group.

Carcinoma, Squamous Cell↗

Improved outcomes with earlier initiation of highly active antiretroviral therapy among human immunodeficiency virus-infected patients who achieve durable virologic suppression: longer follow-up of an observational cohort study.

On the basis of studies with relatively short follow-up, treatment guidelines currently recommend that highly active antiretroviral therapy (HAART) be initiated in asymptomatic human immunodeficiency virus-infected patients when the CD4+ lymphocyte count is < or =200 cells/mm3. We assessed the development of a new opportunistic infection or death among 1173 patients initiating HAART. Durable virologic suppression was defined as having more undetectable (<400 copies/mL) than detectable virus loads after the initiation of therapy. The median durations of therapy and follow-up were 29 and 36 months, respectively. Among patients who achieved durable virologic suppression, those with baseline CD4+ lymphocyte counts of <200 cells/mm3 tended to progress faster than those with baseline CD4+ lymphocyte counts of 201-350 cells/mm3 (P=.09) and progressed faster than those with baseline CD4+ lymphocyte counts of >350 cells/mm3 (P=.01). Among those with durable virologic suppression, there was no difference in disease progression between those with baseline CD4+ lymphocyte counts of 201-350 cells/mm3 and those with durable virologic suppression with baseline CD4+ lymphocyte counts of >350 cells/mm3 (P=.40). Initiating HAART with a CD4+ lymphocyte count of <200 cells/mm3 was associated with a higher risk of disease progression, even with durable virologic suppression. HAART should be initiated at CD4+ lymphocyte counts of >200 cells/mm3.

Adult↗

An artificial intelligence system to predict progression of immune dysfunction in healthy older patients.

In 1983, forty nine participants returning for their annual HEALTH WATCH evaluation were assessed for immune function status and served as healthy controls in an early study of "normal" reference values for T4 and T8 lymphocyte counts and T4/T8 lymphocyte ratios, B lymphocyte counts, and other laboratory tests for immune function then available. Balascopy, a computer-assisted pattern recognition system for detection, quantification and cognition of multiple imbalances among clinical laboratory and health behavioral parameters, facilitates identification of otherwise healthy individuals with evidence of early immune dysfunction. When the T4 and T8 immunology tests were combined with 7 health index behavioral subscores, and 24 routine clinical laboratory tests, we are able to obtain a bodyprint unique for each patient, providing a comprehensive health status profile specific for that individual. These bodyprints serve as tools for the evaluation of otherwise undetectable metabolic, immunological and behavioral imbalances in a given patient in an unprecedented individualized manner. We show here a longitudinal look at a balascopic evaluation of one patient who has evidence of progressive immune dysfunction with development of only mild clinical symptoms.

Aged↗

The acute myocardial infarction in very elderly.

A total 325 patients were studied at admission for myocardial infarction, measuring plasma fibrinogen (FBG), creatine phosphokinase (CPK) and lactate dehydrogenase (LDH) and automatized hemocromocytometric parameters in order to contribute to explain the excess mortality reported in very elderly patients. It was found that age positively correlated with fibrinogen and LDH values and inversely with CPK, hemoglobin concentration and lymphocyte count. The unpaired comparison of the variables studied in age subgroups showed no differences between patients aged 65 or less than 65 years and patients aged 66-75 years. In patients aged over 75 years FBG, neutrophile count and LDH were significantly higher in respect to 65 or less and 66-75 years age subgroups and hemoglobin concentration, red blood cell count, hematocrit and lymphocyte count were lower. In the very elderly patients the study shows a biochemical feature suggesting delayed hospitalization for myocardial infarction, that may contribute to their poorer prognosis.

Journal Article↗

Selective lymphocyte inhibition by FTY720 slows the progressive course of chronic anti-thy 1 glomerulosclerosis.

BACKGROUND: Progression is a hallmark of chronic renal disease and histologically characterized by fibrosis and inflammation of the tubulointerstitial compartment. To define the role of lymphocytes in this process, the novel lymphocyte-specific inhibitor FTY720 was administered to rats with anti-thy 1-induced chronic progressive glomerulosclerosis. In this model, the initial and short-term inflammatory glomerular injury progresses self-perpetuatedly toward tubulointerstitial fibrosis by not primarily immune-mediated, intrarenal mechanisms. METHODS: Chronic progressive glomerulosclerosis was induced by murine anti-thy 1 antibody injection into uninephrectomized rats. Treatment with FTY720 (0.3 mg/kg body weight) was started 7 days after disease induction. Proteinuria was measured every 4 weeks. In week 20, the following parameters were determined: blood lymphocyte number, kidney function, both glomerular and tubulointerstitial histologic matrix accumulation, protein expression of transforming growth factor-beta1 (TGF-beta1), fibronectin, and plasminogen activator inhibitor-1 (PAI-1) as well as infiltration with macrophages and lymphocytes. RESULTS: Treatment with FTY720 lowered blood lymphocyte count and renal lymphocyte infiltration highly significantly. In comparison to the untreated chronic progressive glomerulosclerosis animals, the lymphocyte depletion achieved significantly limited the progression of the disease, as shown by lowered proteinuria, tubulointerstitial matrix expansion, and TGF-beta1, fibronectin, and PAI-1 expression, as well as improved renal function. Glomerular matrix protein expression and accumulation was moderately lowered by FTY720. Glomerular macrophage infiltration was not, tubulointerstitial macrophage infiltration was moderately, but not significantly, decreased by FTY720 treatment. CONCLUSION: Lymphocyte depletion by FTY720 limits the progression of anti-thy 1-induced glomerulosclerosis toward chronic tubulointerstitial fibrosis and renal insufficiency. The data suggest that lymphocytes actively participate in the progression of chronic experimental kidney disease, and that FTY720 may be a novel approach to slow the progressive course of human chronic renal diseases.

Animals↗

Syme ankle disarticulation in patients with diabetes.

BACKGROUND: Syme ankle disarticulation is an amputation level that minimizes disability and preserves function, but it has been used sparingly in patients with diabetes mellitus. Surgeons have avoided this level because of the perceived high risk for wound failure, wound infection, or migration of the heel pad, which makes prosthesis use difficult. METHODS: Ninety-seven adult patients with diabetes mellitus who underwent Syme ankle disarticulation because of a neuropathic foot with an infection or gangrene, or both, during an eleven-year period were studied retrospectively. Selection of the amputation level was made on the basis of clinical examination and an assessment of the wound-healing parameters, i.e., vascular inflow, tissue nutrition, and immunocompetence. The average age of the patients was 53.2 +/- 17.5 years. RESULTS: Eighty-two patients (84.5%) ultimately achieved wound-healing. When threshold levels for vascular inflow (ultrasound Doppler ischemic index of 0.5 or transcutaneous partial pressure of oxygen between 20 and 30 mm Hg) and tissue nutrition (serum albumin of 2.5 g/dL) were met, an overall success rate of 88% was achieved. Total lymphocyte count (an absolute lymphocyte count of 1500) and the smoking of cigarettes during the study period did not appear to impact wound-healing rates. The overall infection rate was 23%, and it was three times greater in smokers. Most infections were managed with local wound care and antibiotic therapy. At a minimum follow-up of two years, all but two patients were able to walk with a prosthesis. Thirty of the ninety-seven patients died at an average of 57.1 months following surgery. CONCLUSIONS: The results of this retrospective review support the value of Syme ankle disarticulation in diabetic patients with infection or gangrene. This function-sparing amputation can be successfully performed with a reasonable risk. Patients managed with a Syme ankle disarticulation appeared to remain able to walk better and to survive longer than similar patients who had a transtibial amputation and served as historical controls. In diabetic patients with dysvascular disease who have adequate vascular inflow to support wound-healing (an ultrasound Doppler ischemic index of 0.5 or a transcutaneous partial pressure of oxygen between 20 and 30 mm Hg), the threshold for the wound-healing parameter of serum albumin appears to be as low as 2.5 g/dL.

Amputation, Surgical↗

Immunosuppressive effects of cyclophosphamide in pigs.

Effects of cyclophosphamide (CY) on circulating leukocytes, lymphoid tissues, and antibody response of the pig were examined. Pigs (10 weeks old) were treated with intraperitoneal injections of 30 mg of CY/kg of body weight at 2-day intervals. Three CY injections depressed total leukocyte, neutrophil, and lymphocyte counts. Circulating B-lymphocyte percentages were depleted by 80% and absolute B-lymphocyte counts by 90%. Circulating T-lymphocyte percentages were not affected by CY treatment, but absolute T-cell counts were depressed by 50%. Lymphocytes were depleted from the cortex of the thymus gland and from the spleen and lymph nodes with a preferential effect on B-dependent areas. All these variables were depressed for the duration of CY treatment and had started to return to within normal values by 4 days after the final treatment. Formation of antibodies to sheep erythrocytes was suppressed in CY-treated pigs until 10 days after inoculation (6 days after final CY treatment); the response of control pigs was detectable 4 days after inoculation. The 6 CY treatments prolonged the depression of all the previously mentioned variables.

Animals↗

Mucocutaneous findings in pediatric AIDS related to degree of immunosuppression.

The normal value of the absolute CD4-positive T-lymphocyte count is relatively high in normal infants and declines steadily until 6 years of age, whereas the CD4 percentage of the total lymphocyte count is constant. The immunologic categories according to the 1994 revised pediatric human immunodeficiency virus (HIV) classification, based on CD4-positive percentage of the total lymphocyte count, is classified into three categories: no evidence of suppression (> or =25%), moderate suppression (15-24%), and severe suppression (1-14%). Our objective was to determine the prevalence of mucocutaneous findings in pediatric acquired immunodeficiency syndrome (AIDS) related to the degree of immunosuppression. We prospectively examined 120 children less than 13 years of age who were born to HIV-seropositive women and developed definite HIV infection. The prevalence of mucocutaneous findings in those children who had severe, moderate, and no evidence of immunosuppression were 62%, 43%, and 20%, respectively. The mucocutaneous findings in patients in the moderate and severe suppression groups were significantly more common than in patients without evidence of immunosuppression (p < 0.001). In the moderate immunosuppression group, 11% had two mucocutaneous findings while 21% in the severe immunosuppression group had two or more mucocutaneous findings. The most common mucocutaneous finding was oral candidiasis (33%), which had a mean corresponding CD4 percentage of the total lymphocyte count of 11.3%. Herpes zoster was found in 6% of the patients (mean CD4 percentage of the total lymphocyte count = 13.5%). Chronic herpes simplex virus (HSV) stomatitis was found in 3% of the patients (mean CD4 percentage of the total lymphocyte count = 3%). Mucocutaneous manifestations are common in pediatric AIDS. The majority of these findings have an infectious etiology. The prevalence increases as the CD4-positive percentage of the total lymphocyte count decreases. More than one mucocutaneous finding can be found at the same time in patients with moderate or severe immunosuppression.

Acquired Immunodeficiency Syndrome↗

[Age and immunity. I. Lymphocyte populations in the peripheral blood in various age groups (author's transl)].

The total lymphocyte count and the different lymphocyte subpopulations were determined in peripheral blood of healthy probands aged 20 to 90 years. With increasing age there is a slow decrease of the total lymphocyte count and of the subpopulations. This was most evident in the decrease in thymus dependent lymphocytes (T cells) which carry cellular immunity. These results support the assumption that with increasing age cellular immunity is clearly reduced and may possibly be associated with an increased incidence of neoplasia, infection, and auto-immune disease. Estimations of lymphocytes and their subpopulations in peripheral blood allow some conclusions as to the immunological resistance which is largely dependent on these cells. Estimation of the number of circulating lymphocytes in relation to age is thus indispensable for the assessment of the immunological reactivity of patients.

Adult↗

Early lymphopenia in burned children with and without the toxic shock syndrome.

The white cell count (WCC) response to thermal injury in children in week 1 postburn has been investigated in a prospective study of 33 patients. Two of these patients developed the toxic shock syndrome (TSS) and, together with seven previously diagnosed cases of the TSS, were studied as a separate group. The WCC response in the non-TSS (control) patients was compared with the response observed in the TSS group. In all patients there was an initial leucocytosis followed by a fall in WCC to a nadir between days 2 and 4. The nadir was significantly lower in the TSS group than that observed in the control group. A rise in the WCC was observed over the following 3-4 days in both groups. In the control group the changes in the WCC were mainly attributable to changes in the granulocyte count with little change in the lymphocyte count. There were similar changes in the granulocyte count in the TSS group but, in contrast to the control group, the lymphocyte count fell, to below the normal range, on day 3. The lowest lymphocyte count observed in the TSS group was significantly lower than that seen in the control group. The observation of a profound fall in the total WCC, granulocytes, and in particular the lymphocytes, between days 2 and 4 are additional factors that may help with the diagnosis of TSS.

Burns↗

Long-term immune dysfunction after radiotherapy to the head and neck area.

BACKGROUND: Hematological side effects are not generally expected due to radiotherapy involving limited radiation fields; however, patients with squamous cell carcinoma of the head and neck (SCCH and N) receiving radiation therapy frequently have chronic intraoral infections. Xerostomia has been implicated as a cause of it, but local or systemic immune alterations are not usually considered. METHODS: With the purpose of evaluating the impact of radiotherapy treatment to different anatomic sites on immune function, 70 patients were evaluated during and after radiotherapy: 50 cases with SCCH and N, 10 with squamous cell carcinoma of the uterine cervix (SCCUC) and 10 patients with central nervous system tumors (CNS). We analyzed lymphocyte counts and T-cell subsets, and over time, their association with the presence of intracellular infections and disease-free survival. RESULTS: Severe lymphopenia was observed in patients with SCCUC and SCCH and N by the fifth week of treatment. Patients with CNS tumors developed mild lymphopenia. In patients with SCCH and N and UC, lower counts were seen in B cells and total T lymphocyte counts including both CD4(+) and CD8(+) cell subsets. The patients with SCCUC recovered lymphocyte counts by the 24th month but T-cell subsets lagged behind. None of the SCCH and N patients had fully recovered by 60 months of follow-up. Recurrence correlates with low lymphocyte counts. DISCUSSION: This work highlights the vulnerability of the head and neck area to the impact of radiotherapy as a reservoir of lymphoid cells. The possibility of recovery as a consequence of thymopoiesis and/or peripheral clonal expansion may limit the antigen-specific recognition of relevant tumor or microbial antigens and cause significant and prolonged immune alterations that may impact long-term survival.

Adult↗

Lymphopenic effect of carbamazepine in a patient with chronic lymphocytic leukemia.

OBJECTIVE: To report a dramatic and reproducible suppressive effect of carbamazepine on circulating lymphocytes in an elderly woman with chronic lymphocytic leukemia. CASE SUMMARY: An elderly woman taking phenytoin for a stroke-associated seizure disorder had lymphocyte count of 28,800 x 10(6) cells/L. Speculating an unusual lymphadenopathic effect of the phenytoin therapy, carbamazepine therapy was substituted. After 15 weeks of carbamazepine treatment, the lymphocyte count declined to 3200 x 10(6) cells/L. Because of severe diarrhea, carbamazepine therapy was stopped and phenytoin therapy was reinstituted. At the end of 4 months of phenytoin treatment, the lymphocyte count had increased to 23,200 x 10(6) cells/L. Phenytoin therapy was discontinued and carbamazepine therapy was begun. The lymphocyte count decreased to 10,700 x 10(6) cells/L. Severe diarrhea recurred and phenytoin treatment was reinstituted. Over 12 days the lymphocyte count increased to 28,900 x 10(6) cells/L. Phenytoin therapy was stopped and valproic acid therapy was started. The lymphocyte count continued to increase during valproic acid therapy, reaching a peak of 114,300 x 10(6) cells/L. DISCUSSION: In this patient with chronic lymphocytic leukemia, carbamazepine therapy had a significant and reproducible lymphopenic effect that was readily reversible upon discontinuation of the drug. Unfortunately, this effect was associated with severe diarrhea, preventing further attempts at exploiting this potentially beneficial action. CONCLUSIONS: Carbamazepine had a reproducible suppressive effect on lymphocyte counts in an elderly patient with chronic lymphocytic leukemia. This unique observation raises the possibility that carbamazepine therapy may have a useful effect in patients with chronic lymphocytic leukemia.

Aged↗

[Relationship between T-subsets and clinical aspects of HIV-associated diseases].

HIV predominantly infects the CD4+ T cells, which during the progression of the disease are eliminated, causing an immune deficiency which renders the patients more susceptible to infections. To evaluate the relevance of the CD4+ T cell elimination and thus the clinical usefulness of CD4/CD8 subset determinations in HIV infected persons, we investigated whether analyses of 667 subset determinations of 365 patients correlated with clinical stages of HIV-infection (CDC classification). Progress of HIV related disease was accompanied by a fall in CD4+ cells and an increase in CD8+ cells, leading to a drastically reduced CD4/CD8 ratio. This change of T-cell subset values correlated well with the clinical classification (CDC). It was, however, only statistically significant if percent values were used, but not if absolute CD4 cell counts, calculated from the peripheral lymphocyte count, were considered. While patients in CDC stage IVC2 (mainly Candida stomatitis) did not differ from stages IIB, IIIB, IVA, we found statistically lower CD4 values if the patients had stage IVA plus IVC2. Stage IVC1 (mainly Pneumocystis carinii pneumonia [PcP, n = 20]) had even lower CD4 values, as PcP appeared almost exclusively in patients with CD4 counts below 20% or 200/microliter. The lowest CD4 counts were observed in patients with Kaposi sarcoma (n = 11) with CD4 cells less than 10% and significant elevated values of CD8 cells (greater than 50%). While the total lymphocyte count correlated with the absolute counts of CD4 and CD8 cells, it was impossible to estimate the T-subset distribution from the absolute lymphocyte count. Our investigations show that a decreased number of circulating CD4 cells correlates well with an increased tendency to develop infections, and thus support the relevance of CD4 cell measurements for the optimal care of asymptomatic HIV infected persons in particular. They also show that the percent values correlate better with clinical stage than the absolute CD4 cell count.

CD4-Positive T-Lymphocytes↗

Hematological changes in the platypus (Ornithorhynchus anatinus) following capture.

Blood samples were collected from the bill sinus of nine free-living platypuses (Ornithorhynehus anatinus) within 12 min of capture of each and again after 1 to 12 hr, New South Wales, Australia, 1981 to 1988. In seven animals which were not anesthetized, there was a significant (P < 0.01) fall in lymphocyte count between the two samples. The reduction ranged from 10 to 58% of the initial lymphocyte count and caused a significant reduction in the total white cell count (P < 0.05). Both the neutrophil and the lymphocyte counts increased in two platypuses which were anesthetized with ether prior to collection of the second blood sample. We propose that the peripheral blood lymphocyte count is a simple means of monitoring the stress response of non-anesthetized, newly-captured platypuses and may be a useful adjunct to behavioral observation.

Animals↗

Immunosuppression in patients with severe acute pancreatitis.

BACKGROUND: In severe acute pancreatitis (SAP), immunologic impairment in the early phase may be linked to subsequent infectious complications. In this study, immunologic alterations in patients with SAP were analyzed, and immunologic parameters related to infectious complications were clarified. METHODS: A total of 101 patients with SAP were analyzed retrospectively. Various immunologic parameters on admission were analyzed and compared between the infection group and noninfection group during SAP. Furthermore, chronologic change in the lymphocyte count was investigated, and its utility for predicting infection was compared with conventional scoring systems. RESULTS: Serum immunoglobulin G (IgG), serum IgM, lymphokine-activated killer cell activity, and natural killer cell activity were low, and the incidence of abnormally low values was 50.0%, 65.0%, 45.5%, and 42.4%, respectively. Serum complement factor 3 was significantly negatively correlated with the APACHE II score. The lymphocyte count was decreased below the normal range, and was significantly negatively correlated with the APACHE II score. CD4-, CD8-, and CD20-positive lymphocyte counts were below the normal range, and CD4- and CD8-positive lymphocyte counts were significantly lower in the infection group. The lymphocyte count on day 14 after admission was significantly lower in the infection group and was more useful for predicting infection than conventional scoring systems. CONCLUSIONS: Immunosuppression occurs from the early phase in SAP, and quantitative impairment of lymphocytes, mainly T lymphocytes, may be closely related to infectious complications during SAP. CD4- and CD8-positive lymphocyte counts on admission and the lymphocyte count on day 14 after admission may be useful for predicting infection.

APACHE↗

Immunological recovery after measles.

Twenty-two children with measles were studied at the stage of the rash and 6 weeks later, and results compared with matched controls. The total lymphocyte count and lymphocyte subpopulations with T- and B-cell markers and those with absence of both markers (null cells) were significantly below control levels in the acute phase. At 6 weeks the B-cell and null-cell counts were still significantly diminished. The function of T cells assessed by 14C uptake of phytohaemagglutinin-stimulated lymphocytes and the delayed skin hypersensitivity reaction to dinitrochlorobenzene was impaired during the acute stage, and this persisted for 6 weeks. Over the 6 weeks of study there was a small but significant rise in serum IgG, IgM and complement factors.

Child↗

Peripheral lymphocyte depletion in gold sodium thiomalate-treated rheumatoid arthritis patients.

It has been reported that gold sodium thiomalate treatment of rheumatoid arthritis reduces the number of peripheral blood lymphocytes. In a prospective, double-blind, randomized trial comparing gold sodium thiomalate, auranofin, and placebo in the treatment of rheumatoid arthritis, we investigated absolute lymphocyte counts. We found that peripheral lymphocyte counts decreased, but there was no correlation with clinical change in disease activity.

Arthritis, Rheumatoid↗

Chronic lymphocytic leukaemia of T cell origin. Clinical variation possibly due to involvement of different T lymphocyte subpopulations.

Based on the literature and 2 patients studied, we suggest that at least 2 different clinical entities are included in the concept of T CLL: (i) a clinical variant characterized by a relatively benign course, splenomegaly without lymphadenopathy, low lymphocyte count and granulocytopenia; the proliferating lymphocyte is morphologically mature, of medium size and a cytoplasm with azurophilic granules staining positively for acid phosphatase and corresponding to parallel tubular arrays as demonstrated by electron microscopy. The cells form E-rosettes, have no surface-membrane-bound Ig, but Fc-receptors for IgG. With monoclonal antibodies, the phenotype is OKT3+, OKT4- and OKT8+, theoretically corresponding to the suppressor/cytotoxic T lymphocyte subset, but functionally the cells demonstrate killer cell (responsible for ADCC), but not natural or suppressor cell activity. (ii) another clinical variant with an aggressive course, massive hepato-splenomegaly, lymph node enlargement and very high lymphocyte counts; the lymphocytes are small without cytoplasmic granules; their immunological and functional characteristics have not been determined, but morphologically the cells correspond to the T helper/inducer lymphocyte subset. Thus, involvement of different T lymphocyte subsets may be the reason for the clinical variation in T CLL.

Aged↗