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Objective To assess survival in cancer patients admitted to an intensive care unit (ICU) with respect to the nature of malignancy, cause of ICU admittance, and course during ICU stay as well as to evaluate the prognostic value of the Acute Physiology and Chronic Health Evaluation (APACHE) III score. Design Retrospective cohort study. Setting ICU at a university cancer referral center. Patients A total of 414 cancer patients admitted to the ICU during a period of 66 months. Interventions None. Measurements Charts of the patients were analyzed with respect to underlying disease, cause of admission, APACHE III score, need and duration of mechanical ventilation, neutropenia and development of septic shock, as well as ICU survival and survival after discharge. Mortality data were compared with two control groups: 1362 patients admitted to our ICU suffering from diseases other than cancer and 2,776 cancer patients not admitted to the ICU. Main results ICU survival was 53%, and 1-yr survival was 23%. The 1-yr mortality rate was significantly lower in both control groups. Patients admitted after bone marrow transplantation had the highest mortality. In a multivariate analysis, prognosis was negatively influenced by respiratory insufficiency, the need of mechanical ventilation, and development of septic shock during the ICU stay. Admission after cardiopulmonary resuscitation yielded high ICU mortality but a relatively good long-term prognosis. Admission after surgery and as a result of acute hemorrhage was associated with a good prognosis. Age, neutropenia, and underlying disease did not influence outcome significantly. Admission APACHE III scores were significantly higher in nonsurvivors but failed to predict individual outcome satisfactorily. All patients with APACHE III scores of >80 died at the ICU. Conclusion A combination of factors must be taken into account to estimate a critically ill cancer patient's prognosis in the ICU. The APACHE III scoring system alone should not be used to make decisions about therapy prolongation. Admission to the ICU worsens the prognosis of a cancer patient substantially; however, as ICU mortality is 47%, comparable with severely ill noncancer patients, general reluctance to admit cancer patients to an ICU does not seem to be justified.

To better understand the clinical significance of changes in lymphocytes in thyroid disease this study analyzed the proportion of CD19+, CD3+, CD4+ and CD8+ cells among circulating lymphocytes in Graves' disease (GD, n = 34) and autoimmune hypothyroidism (AH, n = 28) vs healthy subjects (n = 15). In addition, the expression of CD25 and CD45 isoforms on CD4+ T cells as well as their modulation by methimazole in patients with GD was measured using three color flow cytometry. It was observed that, irrespective of age, both patients with GD (17.6 +/- 7.0% +/- SD) and those with AH (19.0 +/- 9.5%) had an increased percentage of the CD25+CD45RA+ (naive) subpopulation of helper cells vs healthy subjects (7.9 +/- 2.3%, p0.0001). In patients with AH peripheral memory cells and hence overall CD25+ cells were more frequent among helper cells (56.7 +/- 12.2%) than in healthy subjects (40.8 +/- 14.0%, p0.001). Patients with GD (46.2 +/- 13.4%) did not differ from normal subjects in this respect. Treatment of GD with MMI reduced the percentage of CD25+CD45RA+ cells among CD4+ cells toward values seen in healthy subjects. In addition, we confirm previous reports that CD8+ cells toward values seen in healthy subjects. In addition, we confirm previous reports that CD8+ cells are significantly reduced in AH (23.9 +/- 4.9%) and untreated Graves' disease (23.2 +/- 6.6%) vs healthy subjects (32.2 +/- 5.9%, p0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

Background Typhoid fever remains a significant health problem in many developing countries. A rapid test with a performance comparable to that of blood culture would be highly useful. A rapid diagnostic test for typhoid fever, Tubex®, is commercially available that uses particle separation to detect immunoglobulin M directed towards Salmonella Typhi O9 lipopolysaccharide in sera. Methods We assessed the sensitivity and specificity of the Tubex test among Tanzanian children hospitalized with febrile illness using blood culture as gold standard. Evaluation was done considering blood culture confirmed S. Typhi with non-typhi salmonella (NTS) and non - salmonella isolates as controls as well as with non-salmonella isolates only. Results Of 139 samples tested with Tubex, 33 were positive for S. Typhi in blood culture, 49 were culture-confirmed NTS infections, and 57 were other non-salmonella infections. Thirteen hemolyzed samples were excluded. Using all non - S. Typhi isolates as controls, we showed a sensitivity of 79% and a specificity of 89%. When the analysis was repeated excluding NTS from the pool of controls we showed a sensitivity of 79% and a specificity of 97%. There was no significant difference in the test performance using the two different control groups (p > 0.05). Conclusion This first evaluation of the Tubex test in an African setting showed a similar performance to those seen in some Asian settings. Comparison with the earlier results of a Widal test using the same samples showed no significant difference (p > 0.05) for any of the performance indicators, irrespective of the applied control group.

Suramin, a polycyclic and polyanionic drug, has been successfully used in the therapy of inoperable adrenocortical cancer. The present study was undertaken to investigate the effects of suramin on normal human adrenocortical cells in primary monolayer cultures. The proliferation and the basal, as well as the adrenocorticotropin (ACTH)-stimulated, cortisol secretion of these cells were studied. The data show that suramin decreases basal, as well as ACTH-stimulated, cortisol secretion in a dose-dependent manner (P less than .05 from 300 mumol/L upward). At a suramin concentration of 3 mmol/L, cortisol secretion was inhibited by 70% +/- 4% in ACTH-stimulated cells and by 42% +/- 6% in unstimulated cells. The proliferation of adrenocortical cells in response to fetal calf serum was also inhibited by suramin at concentrations from 300 mumol/L upward, maximal suppression (71% +/- 6%, P less than .01) being observed at a concentration of 10 mmol/L. Both inhibition of cortisol secretion and inhibition of adrenocortical cell proliferation were not due to toxicity of the compound, as could be shown by restimulation of cortisol secretion in suramin-treated cells with ACTH. Our results indicate that suramin exerts an inhibitory influence on the cortisol secretion and on the proliferation of normal human adrenocortical cells. Suramin may not only be useful in the treatment of adrenocortical cancer, but may also have an ameliorative effect on other malignant conditions with augmented steroid hormone production, resistant to conventional forms of therapy.

The immunoregulatory influence of transforming growth factor beta (TGF beta) was studied in patients with Graves' disease and in normal controls. Special attention was given to determine how TGF beta affects the interaction between thyroid epithelial cells and T lymphocytes. Human recombinant TGF beta 1 (rTGF beta 1) was immunosuppressive in patients with Graves' disease and in controls. In both groups it inhibited the proliferation of peripheral blood mononuclear cells and of peripheral and thyroid derived T cell lines and clones in response to non-specific stimuli. It also decreased the number of serine esterases expressing cytotoxic T cells and suppressed the recognition of thyroid epithelial cells by thyroid autoantigen specific T cell clones. Inhibition of autoantigen recognition was not only observed when rTGF beta 1 was added to the thyroid epithelial cell/lymphocyte co-culture, but was also found when thyroid epithelial cells were preincubated with rTGF beta 1, which was then removed before the initiation of co-culture. This was probably as a result of a decrease in the antigenicity of the target cells, as rTGF beta 1 also suppressed thyroid peroxidase as well as HLA class II autoantigen expression, in cultured thyroid epithelial cells. These results demonstrate that TGF beta may exert a variety of down-regulatory influences in Graves' disease. It may be of importance for the suppression of autoaggression in persons predisposed to autoimmunity; may be quantitatively overrun by immunostimulatory influences in the acute phase of the disease; and may be important for the induction of remission in patients with Graves' disease.

This study was designed to identify risk factors responsible for postoperative complications after bronchoplastic procedures.Excluding sleeve pneumonectomies between January 1994 and December 2001, 108 patients underwent bronchoplastic procedures for bronchial malignancy. Prospectively documented data were age, gender, side, type of bronchial reconstruction, extended resection, histology, TNM stage, diseased lobe, and bronchial tumour occlusion. Cardiovascular (CV) risk factors included heart disease, arterial hypertension, cerebro-occlusive disease, peripheral artery disease of the lower extremities, diabetes mellitus, and abdominal aortic aneurysm. Patients were grouped according to the presence/absence of any CV risk factor and the absolute number of CV risk factors present (zero to four). Non-CV risk factors included neoadjuvant chemotherapy, alcoholism, lung disease, sleep apnea, history of recent pneumococcal sepsis, and repeat thoracotomy. Groups were assembled according to the presence or absence of any non-CV risk factor, neoadjuvant chemotherapy, and alcoholism. Respiratory risk factors included lung function and blood gas analysis. Groups were assembled according to the absolute number of respiratory risk factors in each person (zero to three) and the combination of respiratory and CV risk factors. Complications were defined as septic (pneumonia, empyema, brochopleural fistula, colitis) and aseptic. For univariate statistical analysis, t test, cross-tabulation, and chi2 test were used. All factors with a significance of p0.1 were entered into a binary backwards-stepwise logistic regression model.The combination of respiratory and CV risk factors (p = 0.012, OR = 0.165) was predictive for overall complications. Coronary artery disease (p = 0.02, OR = 0.062) and the combination of two respiratory risk factors (p = 0.008, OR = 0.062) were predictive for septic complications. Peripheral artery disease (p = 0.024, OR = 0.28), moderate (p = 0.01, OR = 0.13) and severe chronic obstructive pulmonary disease (p = 0.018, OR = 0.11), and extended resections (p = 0.003, OR = 0.017.) were predictive for aseptic complications.Comorbidity significantly influences the postoperative complication rate and is therefore crucial for evaluation of patients for bronchoplastic procedures. Different risk factors are responsible for the occurrence of septic and aseptic complications after bronchoplastic procedures.

Regional differences in immune responsiveness have been studied by comparing the frequency of cytokine producing T cells in healthy African children and adults and their age-matched European counterparts. By use of flow cytometry for the intracellular detection of cytokines an overall expansion of CD4+ and CD8+ T cells producing the Type 1 cytokines interleukin (IL)-2 and interferon (IFN)-gamma was observed in adults when compared with children, giving credit to the cumulative effect of contacts with environmental antigens. The CD4+ cells expressing the Type 2 cytokines IL-4 and IL-13, however, increased only in Africans, probably reflecting continuously present challenges with antigens that preferentially drive Type 2 responses. A striking increased frequency of both Type 1 and Type 2 cytokines producing T cells was found in African adults when compared with their European counterparts. The quantitative and qualitative regional differences in immune reactivity are likely to be of significance for all immune intervention strategies, especially for the design of vaccines.

Study Objective: To assess whether postoperatively administered prostaglandin E 1 (PGE 1 ) might prevent bleeding in patients after coronary artery bypass grafting (CABG). Design: Prospective, randomized, placebo-controlled trial. Setting: University-affiliated hospital. Patients: 49 patients scheduled for elective CABG surgery. Interventions: The PGE 1 group received intravenous PGE 1 up to 15 ng/kg/min for 72 hours after surgery, whereas the placebo group received isotonic saline for the same time period. Measurements and Main Results: Nine patients (4 in the PGE 1 group vs. 5 in the placebo group) had to be excluded because of hemodynamic instability, and 1 in the placebo group because of gastric bleeding. In the remaining 39 patients (20 vs. 19), no significant differences with regard to hemoglobin levels or platelet count could be observed. There was no significant difference between the groups concerning the amount of packed red blood cells, platelet concentrates, or fresh frozen plasma transfused. No significant differences could be observed regarding laboratory markers of coagulation activation or hepatic synthesis either. Conclusions: PGE 1 did not prevent coagulation disturbances and blood loss when administered postoperatively in patients undergoing CABG. The absence of these expected effects might be explained by the concomitant administration of acetylsalicylic acid, whose antiaggregatory acivity seems to exceed the effects of PGE 1 .

Objectives. To investigate the impact of polychemotherapy on cellular immunity in patients with testicular cancer. Methods. Lymphocyte subpopulations, lymphoproliferative responses to mitogenic stimulation, and mitogen-induced release of soluble interleukin-2 receptor from peripheral blood mononuclear cells were investigated in 15 patients with testicular germ cell tumors a median of 61 months (range 7 to 73) after polychemotherapy with bleomycin, etoposide, and cisplatin (BEP). Results. The numbers of peripheral blood T cells (CD3+), CD4+ and CD8+ subsets, and lymphoproliferative responses to pokeweed mitogen, phytohemagglutinin, and concanavalin A in patients were comparable to those of healthy control subjects. When two groups of patients were formed according to elapsed time from BEP polychemotherapy and study onset (group A, 12 months and group B, 69 months after termination of BEP), a significant increase in lymphoproliferative response to concanavalin A (P

Background Cricothyrotomy is the ultimate option for a patient with a life-threatening airway problem. Methods The authors compared the first-time performance of surgical (group 1) versus Seldinger technique (group 2) cricothyrotomy in cadavers. Intensive care unit physicians (n = 20) performed each procedure on two adult human cadavers. Methods were compared with regard to ease of use and anatomy of the neck of the cadaver. Times to location of the cricothyroid membrane, to tracheal puncture, and to the first ventilation were recorded. Each participant was allowed only one attempt per procedure. A pathologist dissected the neck of each patient and assessed correctness of position of the tube and any injury inflicted. Subjective assessment of technique and cadaver on a visual analog scale from 1 (easiest) to 5 (worst) was conducted by the performer. Results Age, height, and weight of the cadavers were not different. Subjective assessment of both methods (2.2 in group 1 vs. 2.4 in group 2) and anatomy of the cadavers (2.2 in group 1 vs. 2.4 in group 2) showed no statistically significant difference between both groups. Tracheal placement of the tube was achieved in 70% (n = 14) in group 1 versus 60% (n = 12) in group 2 (P value not significant). Five attempts in group 2 had to be aborted because of kinking of the guide wire. Time intervals (mean +/- SD) were from start to location of the cricothyroid membrane 7 +/- 9 s (group 1) versus 8 +/- 7s (group 2), to tracheal puncture 46 +/- 37s (group 1) versus 30 +/- 28s (group 2), and to first ventilation 102 +/- 42s (group 1) versus 100 +/- 46s (group 2) (P value not significant). Conclusions The two methods showed equally poor performance.

The systemic inflammatory response syndrome (SIRS) is viewed as a system-wide inflammatory response. Up until now, no parameter has been available for predicting the development of septic shock. In the present study, we evaluated the usefulness of serum levels of CD14, vascular cells adhesion molecule-1 (VCAM-1), endothelial leucocyte adhesion molecule-1 (ELAM-1), macrophage inflammatory protein (MIP) 1 alpha and transforming growth factor beta 2 (TGF-beta 2) as early markers of outcome in patients with SIRS.A group of 28 SIRS patients (13 survivors/15 non-survivors) was compared with a healthy control group and with patients with local inflammation. Blood samples were analysed on days 0, 4 and 7. Proinflammatory parameters such as sCD14, sVCAM-1, sELAM-1, MIP-1 alpha and anti-inflammatory parameters such as TGF-beta 2 were determined using enzyme-linked immunosorbent assay (ELISA).At the beginning, all evaluated proinflammatory immunological parameters with the exception of sVCAM-1 were significantly increased in patients with SIRS compared with the healthy control group. However, no significant difference could be observed for all immunological parameters comparing survivors and non-survivors, with the exception of interleukin (IL) 6 at day 7.All evaluated proinflammatory parameters were increased in patients with SIRS during the course of the disease. However, the parameters have no correlation with outcome and prognosis of SIRS patients.

The aim of the present study was to evaluate the potential prognostic value of MIP-1 alpha, TGF-beta 2, sELAM-1, and sVCAM-1 in patients with gram-positive sepsis. Twenty-eight patients with gram-positive sepsis were compared to 11 patients with gram-negative sepsis and 15 healthy volunteers. Sepsis was defined by the criteria of Bone et al. (Crit. Care Med. 21, 5447-5463, 1993) and by isolation of at least two positive blood cultures with gram-positive/gram-negative bacteria. Plasma samples for determination of the immunological parameters were collected daily. Analysis of cytokines and adhesion molecules was performed on days 0 (day of sepsis criteria fulfillment), 4, and 7 (or 1 day before death). In the gram-positive group 10 of 28 patients died; in the gram-negative group 4 of 11 died. Only sELAM-1 plasma concentrations were found to be a useful early parameter in predicting patients' outcome in gram-positive sepsis. sELAM-1 concentrations at the onset of the study (day 0) were significantly higher in the nonsurviving patients than those in the survivors. MIP-1 alpha levels were significantly higher only on days 4 and 7. With regard to the measured plasma concentrations we believe that MIP-1 alpha is not a useful parameter for predicting patients' prognosis. The increase of sVCAM-1 might play a role in the pathogenesis of gram-positive sepsis; however, it could not be relied upon as an early prognostic parameter. The potential role of TGF-beta 2 in the development of gram-positive sepsis could not evaluated in the present study, whereas routine measurements of TGF-beta 2 offered no additional prognostic information.

SummaryThe records of height on some 700,000 18-year-old Austrian males, called for examination as to their fitness for conscription, were analysed. The data covered 14 conscription years (1980–93), representing males born in the years 1962–75. The sample covered over 90% of the total male population of those cohorts in Austria. The data were analysed by birth year to show the secular trend in 18-year-old stature and its rate, which overall amounted to 0·53 cm/decade. Analysis by urban-rural residence showed that both participated in the trend, but that the urban-rural differences were appeciably less than the differences between the types of school the young men had attended. The rate of increase over the 14 years was less within each of the eight subgroups (urban-rural, four school categories). It is argued that the secular trend in height that has occurred is largely attributable to the change in social stratification, as evidenced by the changed proportion of subjects who attended schools of different...

The mononuclear cellular infiltrate of thyroid neoplasms was examined by immunohistochemical techniques and compared to normal thyroid (control 1) and untreated Graves' disease tissue (control 2). Using a panel of monoclonal antibodies T-, B cells and macrophage antigens as well as the expression of activation-associated antigens and of MHC class II molecules were examined. In comparison to control 1 an increase of positive cells could be detected in carcinomas. This increase was significant for CD3+ and CD8+ T cells, for CD4+ macrophages and for HLA-DP+ cells in all types of carcinomas. In addition, in anaplastic carcinomas a significant increase of B cells, RM3/1+ macrophages, IL-2R+, ICAM-1+ and HLA-DQ+ cells was observed as well as of HLA-DR+ cells in follicular and of CD4+ T cells in papillary carcinomas. A comparison with control 2 revealed a significant increase of CD4+ cells (T cells and macrophages) in papillary and of CD8+ and RM3/1+ cells in anaplastic carcinomas. Our findings, an obvious increase of cell populations and of an upregulated expression of activation-associated antigens on these cells, indicated an immunological reaction caused by neoplastic thyrocytes. Further functional studies are however necessary.

T-T cell interactions are known to be of importance in the generation of immune responses and have been postulated to play a role in autoimmunity. Antiergotypic T lymphocytes are cells, which react with other activated T cells, which they may consecutively neutralize. Antiergotypic T cells have been described to play a role in animal models of autoimmunity and have been found in patients with rheumatoid arthritis. It was the aim of the present study to analyse, whether antiergotypic T cells were also present in the blood of patients with endocrine autoimmunity and to characterize them in vitro. We found that peripheral blood mononuclear cells from patients with Graves' disease, Hashimoto's thyroiditis and Diabetes mellitus show a pronounced proliferative response, when stimulated with autologous T cell lines. This response is dependent on the state of activation of the stimulator cell population, but is independent of its phenotype and is not MHC restricted. In contrast to normal control cells PBMC from patients with endocrine autoimmune disorders respond better to autologous T lymphocytes, than to allogeneic T cells and to autologous E- monocytic cells. T cells responsive to activated autologous T cell lines can also be expanded from PBMC. They may be CD4+ or CD8+ and recognize autologous T cells in the presence of autologous PBMC as feeder cells. These results suggest the presence of a T-T cell network in patients with endocrine autoimmune disease, which may have an important regulatory role in the disease process.

Hair samples of a female orang-utan (Pongo pygmaeus) suffering from Trisomy 22 and three healthy orang-utans had been investigated in regard of their resilience, colour, medulla, cross sectional view, shaft diameter and cuticula structure. There were no characters noticed concerning the orang's hair with Trisomy only. The remarkable sex-specific differences found out in hair shaft diameters have been interpreted as a manifestation of the considerable sexual-dimorphism in orang-utans. The hair samples of all four individuals contain some with an anomaly of the cuticula-structure, which may be seen as an expression of the not species-specific environment in zoos.

Among 165 examined Azande 118 (71.5%) were found with intestinal helminthic infections: Hookworm (69.1%), Schistosoma mansoni (13.9%), Trichuris trichiura (4.2%), Ascaris lumbricoides (1.2%), Strongyloides stercoralis (0.6%). The intradermal Schistosoma test with a commercial antigen preparation was positive in 63.3% of 147 examinees. Protozoa-excretions were found in 62.2% of 151 examines: E. histolytica (27.2%), E. hartmanni (13.2%), E. coli (24.5%), Jodamoeba buetschlii (7.3%), Endolimax nana (1.3%), Lamblia intestinalis (17.2%). Microfilariae were found in 87 of 165 blood-smears (52.7%). The positive diagnoses increased with the age of the examinees. 73.8% of 141 examinees showed an increase of eosinophilic granulozytes up to 11-29%, and 7.8% up to more than 30%. The reliability of the methods used to conserve the test material under extreme conditions as well as the connection between ethnographical situations and the detected parasites are discussed.

Objective: To review the clinical profiles and therapies instituted for patients with severe malaria admitted to an ICU.¶Design: Retrospective study.¶Setting: Internal ICU of a tertiary care centre.¶Patients and participants: Between January, 1992, and February, 1999, 104 patients with malaria were admitted to the General Hospital of Vienna. Sixty-nine patients suffered from Plasmodium falciparum malaria (66 %), seven of these were admitted to the ICU.¶Measurement and results: Seven patients were admitted to the ICU, of whom three died (4 % in hospital case-fatality rate). Four patients required mechanical ventilation because of respiratory insufficiency and adult respiratory distress syndrome (ARDS), of whom three died. Three patients were treated with inhaled nitric oxide (NO) and kinetic therapy; one patient required extracorporeal veno-venous oxygenation. All patients who died required haemofiltration because of acute renal failure.¶Conclusion: As P. falciparum is a potentially life-threatening disease, reliable criteria for ICU admission should be defined and risk factors identified. Early ICU monitoring should be attempted, especially under the following conditions: (1) lack of clinical response to anti-malarial treatment within 48 h and/or (2) any signs of neurological disturbance (hypoglycaemia excluded). Prospective multicentre trials and guidelines for supportive intensive care are urgently needed.

Immunotherapy with intravenous recombinant human interleukin-2 (rh IL-2) may be accompanied by hypotension and the emergence of capillary leak syndrome. Nitric oxide (NO) is supposed to be responsible for both side effects. The aim of the current investigation was to elucidate the relationship between pro- and anti-inflammatory cytokines and the production of NO in eight tumor patients receiving intravenous rh IL-2 continuously over a time period of 120 hours. Markers of systemic inflammation, as well as nitrate plasma levels, were consecutively determined. Significant changes in the levels of pro-inflammatory cytokines IL-6 and IL-8 were observed (p0.05). In contrast to the anti-inflammatory cytokine IL-10, which did not increase significantly, the serum concentrations of the soluble tumor necrosis factor receptors (sTNFr) I and II rose continuously and significantly during the observation period (p0.05). In parallel, a significant rise in nitrate plasma levels was observed (p0.05). Moreover, there were highly significant correlations between nitrate and IL-6 serum levels (p0.05), nitrate and sTNFr-I (p0.05), nitrate and sTNFr-II (p0.05), and between IL-6 and IL-10 (p0.05), respectively. We conclude that immunotherapy with IL-2 promotes a pro-inflammatory state, parallelled by an increased production of nitric oxide. Although anti-inflammatory responses accompany this process, they are not able to diminish the production of nitric oxide.