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PubMed1996

A case of cryofibrinogenaemia responsive to stanozolol.

Cryofibrinogen is a plasma protein complex whose presence in the peripheral blood is generally asymptomatic, but may sometimes cause multiple thromboembolism in the skin, lung and myocardium. The pathological manifestations associated with cryofibrinogenaemia have been treated with plasmapheresis and fibrinolytic drugs such as streptokinase, streptodornase and/or urokinase. Good results have recently been reported with stanozolol. This prompted us to treat a patient suffering from cryofibrinogenaemia with this androgenic hormone. The patient was a 66-year-old woman with rapidly evolving leg ulcers. Stanozolol was orally administered at 4 mg b.i.d. for 5 months and then gradually reduced. Plasma cryofibrinogen disappeared after 45 d from the start of therapy and cutaneous ulcers healed in 5 months.

Aged↗

PubMed1986

Host defense mechanisms in elective and emergency vascular surgery: predicting septic-related mortality.

This study examines host defense mechanisms in vascular surgery patients when admitted to the hospital to determine the frequency of abnormal host defense and the predictability of this information for septic-related mortality in affected patients. Sixty-four patients undergoing elective surgery (indications: 35 with aneurysms, 27 with aortoiliac disease, and two with renovascular disease) and nine patients undergoing emergency operation (indications: two with ruptured aneurysms, seven with aortoenteric fistulas) were skin tested when admitted to the hospital with five ubiquitous antigens (Candida, mumps, tuberculin, Trichophyton, and streptokinase-streptodornase [Varidase]) and read at 24 and 48 hours. Patients were anergic with none, relatively anergic with one, or reactive with two or more antigen responses (induration 5 mm). Eighty-nine percent of elective surgery patients were reactive, 5% were relatively anergic, and 6% were anergic. This compared with 64% reactive, 13% relatively anergic, and 17% anergic patients in a separate concurrent study of 565 surgical patients with gastrointestinal malignancies (p less than 0.001, chi 2). There were two septic-related deaths in the elective surgery group and both patients were anergic at admission, which resulted in a mortality rate of 50%. Two deaths not related to sepsis occurred in two reactive patients (4%). Logistic regression analysis predicted 3.9 deaths in the elective surgery group and four deaths were observed. Both patients with ruptured aneurysms were unreactive and both died of septic-related complications. Only one of seven patients admitted with an infected graft was reactive. All had surgery. Using the admission data of these seven patients, we predicted 2.3 deaths. Two deaths were observed 21 and 48 days after operation. Both patients were anergic and scored high probabilities of mortality (more than 0.6) at admission. The remaining emergency procedure patients scored lower probabilities of mortality (less than 0.4) at admission and none died.2+.

Adult↗

PubMed1982

Immunocompetency in anorexia nervosa.

Twenty-two consecutively admitted patients diagnosed for anorexia nervosa were evaluated for cellular immune functioning by means of an anergy panel to test delayed hypersensitivity. The panel included candida, streptokinase-streptodornase, and mumps antigen administered by a standard protocol. A standard nutritional profile including current weight, usual weight, total protein, albumin, total iron-binding capacity, white blood cell count, total lymphocyte count, triceps skinfold, and arm muscle circumference was concurrently compiled on these subjects. Six of 22 patients studied were anergic. Visceral protein measures were generally within normal limits even in the most depleted patients. Malnutrition as measured by severity of weight loss and triceps skinfolds was significantly related to anergy, whereas visceral protein indicators (serum albumin, total iron binding capacity, transferrin) were not correlated with anergy. Anergy appeared to be related more strongly to anthropometric indices of malnutrition than to visceral protein values. Cellular immunity was generally preserved until weight loss was far advanced.

Adult↗

PubMed1981

Immunomodulating properties of dimethylglycine in humans.

Dimethylglycine (DMG), a tertiary amino acid, has had wide acceptance as a nonfuel nutrient; presumably it enhances oxygen utilization by tissue and complexes free radicals. Its potential as an immunoadjuvant has also been suggested by a study of an analog of DMG, calcium pangamate. A double-blind study in 20 human volunteers showed a fourfold increase in antibody response to pneumococcal vaccine in those receiving DMG orally as compared with controls (P less than 0.01). Production of leukocyte inhibitory factor in response to concanavalin A was similar in the two groups, but those taking DMG tablets had a significantly highr mean response of leukocyte inhibition factor to streptokinase-streptodornase (P less than 0.001). The in vitro responses of lymphocytes from patients with diabetes and those with sickle cell disease to phytohemagglutinin, convanavalin A, and pokeweed mitogen were increased almost threefold after addition of DMA. These results suggest that DMG enhances both humoral and cell-mediated immune responses in humans.

Adjuvants, Immunologic↗

PubMed1981

The "in vitro skin test": a reliable and repeatable assay of immune competence in the surgical patient.

In vitro blast transformation of human peripheral lymphocytes was tested using standard skin test antigens, the mitogens PHA and Con A, and the mixed lymphocytes reaction. The study group included 15 patients with multiple trauma, 40 with major burns, six following cholecystectomies, six following aortic reconstruction, and 30 normal volunteer controls. Repeated skin testing may sensitive patients to candida and streptokinase-streptodornase (SKSD), and desensitize them to mumps antigen. Blast transformation in response to PPD did not correlate with the clinical status of the patients; similarly, blast transformation in response to stimulation by the mitogens PHA and Con A could not reliably predict the occurrence of septic complications. Reactivity in response to stimulation by the soluble antigens SKSD and mumps and in the one-way mixed lymphocyte reaction accurately predicted the clinical course of patients. This method of "in vitro skin testing" is a reliable and repeatable method of monitoring the immunologic status of patients whose illness or injury requires longitudinal study.

Antigens↗

PubMed1987

Bacterial colonization of intravascular catheters and anergy to recall skin antigens.

The skin reactivity of 46 ICU patients was tested against recall antigens: mumps, candidin, streptokinase-streptodornase, and purified protein derivative of tuberculin. At the same time, the intravascular catheters used in these patients were cultured with a semiquantitative method. Twelve patients did not react to any of the antigens. There was a statistically significant association between anergy in skin testing and lethal outcome of the current illness. Catheter cultures from 11 patients yielded over 15 colony-forming units of bacteria. No association was found between positive catheter cultures and skin reactivity to any of the antigens. This indicates that catheter colonization is independent of host factors reflected by skin testing and supports the view that transmission of microorganisms into catheters is more important than poor host defense in the initiation of catheter-related infections.

Aged↗

PubMed1979

Cellular immunity in renal diseases.

Cellular immune reactivity was studied in 78 patients with various forms of renal disease by skin testing with four recall antigens and a lymphocyte transformation test with tuberculin PPD and leucoagglutinin. Patients with S-creatine greater than or equal to 230 micromol/l as well as those with chronic pyelonephritis who had S-creatinine values below 230 micromol/l had significantly lower skin reactions than the controls to streptokinase-streptodornase, parotitis and PPD. Glomerulonephritic patients with S-creatinine values below 230 micromol/l had normal skin reactivity. Lymphocyte transformation tests showed decreased reactivity only in patients with S-creatinine level greater than or equal to 230 micromol/l. The results suggest an association of chronic pyelonephritis with a defective efferent, nonspecific arm of cellular immunity.

Adult↗

PubMed1975

Effects of intensive application of retinoic acid on human skin.

The daily application of 0-3% retinoic acid to the back produced an acute irritant dermatitis which resolved to a near-normal clinical appearance within 40 days despite continued daily exposure. Hardened skin was markedly altered physiologically. The responses to DMSO, histamine and the histamine liberator, compound 48/80, were sharply enhanced. This reflected enhanced permeability resulting from reduction of the horny layer to less than one-half its normal thickness. Phototoxic and irritant substances produced exaggerated reactions owing to greater penetration. A paradoxical decrease in delayed sinsitivity to streptodornase-streptokinase was attributed to enhanced clearance of the antigen.

Adult↗

PubMed1990

Beneficial effects of the thymic hormone preparation thymostimulin in patients with defects in cell-mediated immunity and chronic purulent rhinosinusitis. A double-blind cross-over trial on improvements in monocyte polarization and clinical effects.

Twenty patients with chronic purulent rhinosinusitis were treated with TP-1 (Serono; 1 mg/kg body weight), in a double-blind cross-over trial. TP-1 was administered by daily i.m. injections for the first 14 days followed by two injections/week for 6 further weeks. The patients were immunologically special in that they had defects in their cell-mediated immune system. Fourteen showed a decreased chemotactic responsiveness of their peripheral blood monocytes as measured in the polarization assay. This defective function can probably be ascribed to the presence in serum of low molecular weight factors (LMWFs; less than 25 kD). As reported earlier, this factor shows a structural homology to the envelope protein of murine and feline leukaemia virus (P15E). Thirteen patients showed a defective delayed-type hypersensitivity (DTH) skin test reactivity towards candidin and/or streptokinase-streptodornase (Sk/Sd) antigen, 14 had a defective MIF production from their peripheral blood lymphocytes towards candidin, Sk/Sd and/or Haemophilus influenzae antigen. Eighteen patients completed the TP-1 trial and showed clinical improvements: 12 out of 15 were feeling better during TP-1 therapy and the nasal mucosa showed on inspection absent mucopurulent secretion in 13 patients. Positive bacterial culture rates for the nose decreased from 14 out of 16 to five out of 15. Placebo treatment had no significant effects. The clinical improvements were accompanied by a better performance of the cell-mediated immune system; the most significant effects were recorded in the monocyte polarization assay. The suppressive P15E-like LMWFs in serum clearly decreased during TP-1 treatment. In vitro TP-1 neutralized the immunosuppressive effect of the LMWFs. The restoring effects of TP-1 on monocyte polarization and its neutralizing activity of P15E-like LMWFs could explain the beneficial effects of thymic hormone treatment reported in adults with clinical signs of immunodeficiency in the presence of a full T cell repertoire.

Adult↗

PubMed1991

Normal and sarcoid alveolar macrophages differ in their ability to present antigen and to cluster with autologous lymphocytes.

Human bronchoalveolar macrophages from normal individuals function poorly as accessory cells for the presentation of common recall antigens. In sarcoidosis, alveolar macrophages (AM) are reported to be effective accessory cells for the presentation of such antigens. In this study normal and sarcoid AM were compared with blood monocytes for their ability to act as accessory cells in presenting tuberculin purified protein derivative (PPD) and streptokinase-streptodornase (SKSD) to autologous T lymphocytes, or to form spontaneous, antigen- or mitogen-induced clusters with the T cells. When compared to autologous monocytes, normal AM failed to present the two recall antigens effectively. Likewise normal AM formed very few clusters with T lymphocytes when compared to monocytes, even in the presence of antigens or the mitogen phytohaemagglutinin (PHA). In contrast, sarcoid AM presented both antigens as effectively, and were equally effective as monocytes in forming clusters with T lymphocytes, spontaneously and in further response to antigen or mitogen. The results suggest that in sarcoidosis enhanced accessory cell function and enhanced cluster formation may be related features of bronchoalveolar macrophage populations.

Adolescent↗

PubMed1995

The immunosuppressive drug thalidomide induces T helper cell type 2 (Th2) and concomitantly inhibits Th1 cytokine production in mitogen- and antigen-stimulated human peripheral blood mononuclear cell cultures.

Thalidomide is an effective immunomodulatory drug in man, but its mechanism of action remains unclear. We hypothesized that, in addition to its reported inhibitory effects on production of monocyte-derived tumour necrosis factor-alpha (TNF-alpha), thalidomide might be effective at the level of Th immunoregulation. In a comparative study with the immunosuppressant cyclosporin A, we have demonstrated a potent and specific effect of thalidomide on cytokine production relating to the distinct Th1 and Th2 subsets. It induced and enhanced the production of IL-4 and IL-5 and, at the same dose (1000 ng/ml), significantly inhibited interferon-gamma (IFN-gamma) production in phytohaemagglutinin (PHA)-stimulated human peripheral blood mononuclear cell (PBMC) cultures. Stimulation of PBMC with recall antigen (streptokinase:streptodornase (SKSD)) at 144 h in the absence of thalidomide resulted in a predominantly Th1 response, with the production of IFN-gamma and IL-2. Thalidomide switched this response from a Th1 to a Th2 type. The effect was most pronounced at 1000 ng/ml thalidomide, where inhibition of IFN-gamma and enhancement of IL-4 production was maximal. In unstimulated cultures thalidomide alone induced IL-4 production. Cyclosporin A, in contrast, inhibited both Th1 and Th2 cytokine production by PHA-stimulated PBMC. Time course data from thalidomide-treated cultures revealed that the augmented IL-4 production diminished as the culture time increased, whereas IFN-gamma production was significantly increased. This response might be due to activation-induced apoptosis of Th2 cells or the induction of Th2 cell anergy, in the continued presence of stimulating agents, with the emergence of IFN-gamma-secreting Th1 cells when Th2 antagonism declines. The effects of thalidomide and related compounds may enhance our understanding of the mechanisms of T helper cell selection, offer the possibility of controlled therapeutic switching between Th1 and Th2 responses, and may lead to a rational approach for the treatment of some T cell-mediated immunological disorders.

Cells, Cultured↗

PubMed1982

Use of tetanus toxoid for testing cell-mediated immunity.

Tetanus toxoid was assessed as a skin test antigen for the measurement of cutaneous delayed-type hypersensitivity (DTH) by comparing the responses to intradermal injections of aqueous tetanus toxoid and an extract of Candida albicans in 50 randomly selected healthy adults and 10 adults with immunodeficiency. Of 42 healthy subjects previously immunised with tetanus toxoid, 33 (79%) reacted to tetanus toxoid and 33 (79%) reacted to Candida albicans. Of eight non-immunised subjects, none reacted to tetanus toxoid although five reacted to Candida albicans. Ten immunodeficient adults previously shown to be anergic to a standard panel of five skin test antigens including Candida albicans, and who had received primary immunisation and booster doses of tetanus toxoid, were anergic on current testing with tetanus toxoid and Candida albicans. Tetanus toxoid in previously immunised subjects has certain advantages as a "recall" DTH test antigen over the standard skin test antigens candidin, mumps, trichophyton, tuberculin and streptokinase-streptodornase used to diagnose cell-mediated immuno-deficiency. It is a sensitive measurement of DTH, it recalls a defined immunological event, it has a low incidence of side effects, and it produces a slight but beneficial boosting of serum antibody to tetanus toxoid.

Adenocarcinoma↗

PubMed1982

Immunological profile of patients with transitional cell carcinoma of the bladder.

The immunological profile of 58 patients with various stages of transitional cell carcinoma of the bladder was determined by using the local xenogeneic graft versus host reaction (GVHR) test, by skin testing with 3 recall antigens (candida, trichophyton, streptokinase-streptodornase) and by quantification of T-lymphocytes. Thirty-two patients with low grade low stage tumours (Group A) showed only a slight impairment of the immunological profile with a slight decrease in T-lymphocytes, 4.4% negative GVHR tests and 31.2% negative skin tests. Ten patients with highly invasive inoperable tumours (Group B) showed a severe impairment of the immunological profile with a significant decrease in T-lymphocytes, 100% negative GVHR and 80% negative skin tests. A marked improvement in the immunological profile was noted while comparing 9 patients who were examined within 6 months after cystectomy (Group CI) (severe decrease in T-lymphocytes 44.4% negative GVHR tests and 66.6% negative skin tests) with 7 patients who were examined 18 months or more after operation (Group CII) (slight decrease in T-lymphocytes 0% negative GVHR and 42.8% negative skin tests). Incubation of T-lymphocytes with a thymic hormone (THF) caused an increase in the extent of the graft versus host reaction in 10 out of 14 patients with low grade low stage bladder tumours. This may represent an improvement in the functional activity of the T-lymphocytes with a possible therapeutic use in the future.

Adult↗

PubMed1983

Persistent cutaneous cellular immune responsiveness in a nursing home population.

Mantoux-type skin tests were applied to 29 elderly residents of an intermediate care floor of a nursing home. Eight antigens were used with each resident, and the size of the reactions was measured at 6, 24, 48, and 72 hours. All but one resident had at least one response greater than or equal to 3 mm at 48 or 72 hours, and most had more than one response of that size. At 48 compared with 72 hours, there was one more responder and the mean size of the reactions to each antigen was greatest. However, there were two responders at 72 hours who did not react at 48 hours, and the total number of reactions in the group was greater at the later reading. Only one resident did not produce any response at either 48 or 74 hours. The minimum number of antigens needed to identify all responsive subjects was five (PPD-Avian, coccidioidin, histoplasmin, streptokinase-streptodornase, and trychophytin). The purified protein derivative of tuberculin skin test was repeated on subjects who had an initial response less than 10 mm, and one increase of more than 6 mm was observed in a resident who was initially unresponsive to that antigen.

Aged↗

PubMed1979

A statistical analysis of human lymphocyte transformation data.

The lymphocytes from 107 maternal-foetal pairs were examined for their in vitro responsiveness, as determined by the incorporation of tritiated thymidine following stimulation with phytohaemagglutinin (PHA), candida, varicella, mumps, streptokinase-streptodornase (SKSD) and tetanus toxoid. The data were collected and analysed in two sequential groups (forty-seven and sixty) in order to determine whether the results were reproducible. The variable chosen for analysis was the difference (d) between the square roots of the isotope incorporation in the stimulated and control cultures because it gave the most symmetrical distribution of the data. The experimental error in the determination of maternal lymphocyte stimulation was 1.4--8.6% and of the foetal lymphocytes, 1.0--16.6%, depending upon the antigen or mitogen and its concentration. The data in the two sets of patients were statistically the same in forty-eight of the fifty-six analyses (fourteen antigen or mitogen concentrations in autologous and AB plasma for maternal and foetal lymphocytes). The statistical limits of the distribution of responses for stimulation or suppression were set by an analysis of variance taking two standard deviations from the mean as the limits. When these limits were translated into stimulation indices, they varied for each antigen or mitogen and for different concentrations of the same antigen. Thus, a detailed statistical analysis of a large volume of lymphocyte transformation data indicates that the technique is reproducible and offers a reliable method for determing when significant differences from control values are present.

Adult↗

PubMed1979

Relationship between the responsiveness of maternal and foetal lymphocytes to phytohaemagglutinin and to microbial antigens.

The response of 105 maternal-foetal lymphocyte pairs to specific and non-specific stimulation were evaluated using a newly defined method of analysis. There were no significant differences in the responses of maternal or foetal lymphocytes to phytohaemogglutinin (PHA) or the various antigens as a function of concentration over the ranges tested. The maternal lymphocytes were stimulated by all of the antigens and responded to PHA three--five times more strongly than to the antigens. The foetal lymphocytes were stimulated by PHA and tetanus toxoid only and were suppressed by streptokinase-streptodornase (SKSD). They responded to stimulation by antigens at a lower level than did the maternal lymphocytes, but they responded at a much higher level to PHA. Unstimulated cultures of foetal lymphocytes incorporated more isotope than did those of maternal lymphocytes in both autologous and AB plasma. The data were cross-classified to determine whether the responses of the foetal lymphocytes varied concordantly with the responses of the maternal lymphocytes in both autologous and AB plasma by the Chi-square test for independence and by rank correlation analysis. There was no significant correlation in either plasma to stimulation with the antigens. Thus, the presence of antigen reactive lymphocytes in the circulation of the mother does not mean that the foetus is sensitized to that antigen. Comparison of the lymphocyte responses in autologous plasma with those in AB plasma provided evidence for the presence of circulating immunoregulatory substances. Autologous maternal plasma suppressed the lymphocyte responses to high concentrations of candida and SKSD and stimulated the response to mumps, varicella and tetanus toxoid. Autologous fetal plasma suppressed the lymphocyte responses to candida, varicella and SKSD and stimulated the response to PHA. The responsiveness of maternal lymphocytes to PHA was less in foetal plasma than in autologous maternal or AB plasma.

Adult↗

PubMed1978

Amphotericin B and 5-fluorocytosine: in vitro effects on lymphocyte function.

The effects of amphotericin B, 5-fluorocytosine, and the combination of both drugs on lymphocyte function in vitro were investigated. Amphotericin B, alone or in combination with 5-fluorocytosine, significantly suppressed both spontaneous lymphocyte transformation and the response of lymphocytes to stimulation with streptokinase-streptodornase. 5-Fluorocytosine had no effect on spontaneous or antigen-induced transformation. Lymphocyte responses to the mitogens phytohemagglutinin and concanavalin A were not changed by exposure to amphotericin B, 5-fluorocytosine, or the combination of both drugs. T-lymphocyte receptors for sheep erythrocytes and B-lymphocyte surface immunoglobulin and receptors for complement were not changed by treatment with amphotericin B or 5-fluorocytosine.

Amphotericin B↗

PubMed1976

Blastogenic response of human lymphocytes to oral bacterial antigens: characterization of bacterial sonicates.

Soluble sonicate supernatant preparations were made from Actinomyces viscosus (ATCC 19246), A. naeslundii (ATCC 12104), two strains of Veillonella alcalescens (strain HV-1 and a human oral isolate), Streptococcus sanguis (ATCC 10556), S. mutans (strain 6715-T2), Bacteroides melaninogenicus (strain K110), and Leptotrichia buccalis (isolated from human dental plaque). These supernatants were characterized with reference to their chemical and antigenic components and their biological activity determined by using in vitro lymphocyte blastogenesis as a measure of the host's cellular immune response. The sonicate supernatant of each bacterium contained protein, neutral sugars, methylpentose, and nucleic acids. Protein was the major component in all except L. buccalis, in which neutral sugars predominated. The antigenic components in each supernatant were detected by using rabbit antisera prepared against the whole bacteria and the sonicate supernatant. The supernatants showed a complex antigenic distribution on immunoelectrophoretic analysis. The supernatants were shown to be antigenic and not mitogenic in nature, since neither cord blood lymphocytes nor all adult lymphocytes were stimulated. The supernatant antigen preparations showed a reproducible, dose-dependent, and kinetic response in vitro, which was similar to that seen with the antigen preparation streptokinase-streptodornase.

Actinomyces↗