Occupational exposure to cytostatic fumes during hyperthermic intraperitoneal chemotherapy.

Hyperthermic intraperitoneal chemotherapy (HIPEC)-heated, intra-abdominal chemotherapy-has become the treatment of choice for treating peritoneal metastases from ovarian, stomach or colorectal cancers. HIPEC has several advantages and disadvantages. The major benefit is minimal systemic toxicity for the patient, but there is a risk of occupational exposure for operating room staff. We have not found any reports of workers with chronic aplastic anaemia as a result of exposure to cytostatic fumes during HIPEC. The aim of this case report is to raise the awareness of potential negative health effects of inhalation exposure to cytostatic drugs. We present a rare case of a 43-year-old woman, suffering from aplastic anaemia as a long-term consequence of exposure to cytostatics. During the HIPEC procedure, surgical revision of the peritoneal cavity was undertaken which resulted in release of cytostatic fumes. Despite awareness of the health effects of occupational exposure to cytostatic drugs and well-developed procedures for safely handling them, unexpected exposure may occur causing serious medical conditions. These may develop in sensitive subjects although accidental high-level exposure may lead to unexpected long-term consequences in all workers. Medical staff need to be informed of the risks of HIPEC and safety guidelines to reduce the risk of exposure.

The relationship between serum level of N-terminal pro-B-type natriuretic peptide and nutritional status, and inflammation in chronic hemodialysis patients.

BACKGROUND: N-terminal pro-B-type natriuretic peptide (NT-pro BNP), a biomarker of heart failure, is involved in regulation of the body fluid homeostasis and vascular tone. The purpose of this study was to investigate the relationship between serum level of NT-pro BNP and nutritional status, inflammation and hydration in patients on maintenance hemodialysis (HD). MATERIALS AND METHODS: The study involved 97 HD patients (mean age: 65.3 +/- 13.9 years, HD duration: 36.3 +/- 43.5 months). Blood tests comprised the measurements of serum levels of NT-pro BNP, interleukin-6 (IL-6), human soluble tumor necrosis factor receptor I (s TNF RI), hemoglobin (Hb), albumin (alb) and urea. Furthermore, normalized protein catabolic rate (n PCR), body mass index (BMI), mean arterial blood pressure (MAP), adequacy of HD (Kt/V), and interdialytic body weight gain (IBWG) were calculated. In addition, NT-pro BNP was measured in a healthy control group (CG; n = 24, mean age 49.5 +/- 15.0 years). Hydration status was determined by bioimpedance analysis (BIA). RESULTS: Irrespective of gender, NT-pro BNP levels were markedly elevated in HD patients compared with CG (15879.2 +/- 14033.3 pg/ml vs. 73.45 +/- 23.56 pg/ml; p < 0.00001). NT-pro BNP was unrelated to any measures of body fluid compartments. Multivariate regression analysis revealed that only four parameters (nPCR, Hb, MAP, and total time on HD) influenced serum NT-pro BNP levels. CONCLUSION: While there was only moderate direct association of NT-pro BNP with hydration status, it was elevated in patients with intensive catabolism, severe anemia, higher MAP and longer total duration of HD.

Immunohistopathology of lymph nodes in HTLV-III infected homosexuals with persistent adenopathy or AIDS.

Lymph node biopsies from 43 male homosexuals with persistent generalized lymphadenopathy and from ten acquired immunodeficiency syndrome patients, all with serum antibodies to human T-cell leukemia virus III, were studied with regard to histopathology, immunohistology, and T-cell subsets in cell suspensions. All acquired immunodeficiency syndrome biopsies except one with Kaposi's sarcoma had the same histopathological pattern of follicular depletion, whereas the persistent generalized lymphadenopathy nodes showed a spectrum of changes characterized as follicular hyperplasia, involution with follicular fragmentation, or involution with follicular atrophy. Immunohistology showed a temporal and structural relation between follicular involution, disappearance of follicular dendritic reticulum cells, and follicular invasion by T-cells. These observations suggest elimination of dendritic reticulum cells as part of a pathogenic mechanism in follicular involution. Angiogenesis measured by staining of endothelial cells with antibodies to Factor VIII was increased in many biopsies in stages of involution and depletion. Our observations indicate the occurrence of marked changes not only in T-cells but also in the B-cell compartment of patients with persistent generalized lymphadenopathy or acquired immunodeficiency syndrome. The possibility of staging lymph nodes of these patients by combined histopathology and immunohistology is indicated. This might improve the evaluation of prognosis in these patients. A possible importance of angiogenesis for the tumorigenesis of Kaposi's sarcoma is suggested.

Low-T3 syndrome and signal-averaged ECG in haemodialysed patients.

The study was designed to evaluate the potential link between low-T3 syndrome and signal-averaged ECG parameters (SAECG) in a group of hemodialyzed patients (HD-pts). 52 selected HD-pts (without relevant thyroid and cardiac diseases) were included. SAECGs were performed postdialysis together with evaluating free triiodothyronine (fT3), free thyroxine (fT4), reverse triiodothyronine (rT3), thyroid stimulating hormone levels and echocardiography. For each SAECG, QRS duration (QRSd), root-mean-square voltage of the terminal 40 ms of the QRS (RMS40), and low-amplitude signal duration (LAS40) were measured. Abnormal SAECGs were found in 30.8 % of HD-pt. HD-pts with decreased fT3 and increased rT3 values (low-T3 positive) revealed higher QRSd and LAS40 values in comparison with low-T3 negative HD-pts (p = 0.019, p < 0.001 respectively). Low-T3 positive HD-pts had lower RMS40 values than low-T3 negative patients (p < 0.001). The Pearson test showed significant correlations between QRSd and fT3 (r = -0.592, p < 0.001); QRSd and rT3 (r = 0.562, p < 0.001); RMS40 and fT3 (r = 0.432, p = 0.009); RMS40 and rT3 (r = -0.325, p = 0.025). On multivariate analysis, both fT3 and rT3 levels were found to be independent predictors of QRSd and RMS40 values. Our study showed that decreased fT3 and increased rT3 concentrations due to low-T3 syndrome influence SAECG parameters in HD-pt.

Rate of Staphylococcus aureus nasal carriage in immunocompromised patients receiving haemodialysis treatment.

Specimens from the nose and throat were collected from 28 long-term haemodialysed patients. Staphylococcus aureus strains were isolated from sixteen patients who been on haemodialysis for over 113 months. Cytokine levels, as well as full blood cell differential counts and cell surface antigens were determined in these patients. The serum concentration of TGF-beta was significantly higher in patients carrying Staphylococcus aureus. CD14 and HLA-DR molecule expression on monocytes, as well as NK cell percentage was significantly different in S. aureus carriers. Our preliminary results suggest that immune status imbalance in haemodialysed patients could be related to the high incidence of S. aureus nasal carriage and infections.

Effect of recombinant human erythropoietin on adrenergic activity in normotensive hemodialysis patients.

Ten normotensive hemodialysis patients with severe anemia participated in the study. Human recombinant erythropoietin (rHuEpo) was administered i.v. 3 times a week in doses of 50 U/kg of body weight. During 12 weeks of observation, the mean hematocrit value increased from 19%, before start of therapy, to 32%. Simultaneous monitoring of serum plasma noradrenaline (NA) concentration showed an elevation from 202 to 281 pg/ml. An increase of NA concentration after a cold pressure stimulating test (CP) was not statistically significant after as compared to before treatment, but became statistically significant after 12 weeks of rHuEpo therapy (281 pg/ml before to 441 pg/ml after CP test, p < 0.01). The mean arterial blood pressure increased from 92 - 109 mmHg after 12 weeks of rHuEpo therapy (p < 0.001). We have demonstrated significantly increased NA blood concentrations after 12 weeks of rHuEPO therapy in normotensive patients, which correlated with increased MAP. This may suggest that the observed increase of noradrenaline concentration as a vasoactive substance after the CP test may contribute to hypertension during rHuEPO therapy.

Kinetics of continuous ambulatory peritoneal dialysis (CAPD) with four exchanges per day.

Fourteen patients who had no signs of peritonitis were studied during CAPD. Different exchange time schedules were used alternating exchanges with 1.5% and 2.6% glucose solutions. Usually longer exchanges followed shorter ones and vice versa. Total exchange time varied from 2--10 hours. Maximal ultrafiltration volumes were observed after 3 hours with 1.5% and 5 hours wit 2.6% glucose solutions. For small molecular weight solutes (urea, creatinine, sodium, potassium, and phosphate) dialyzate to plasma concentration ratios tended to be lower with 2.6% glucose solutions during the shorter exchanges. Equilibrium between plasma and dialyzate was attained for all these solutes by 10 hours total exchange time. The concentration ratios for inulin were similar with both types of solution, and did not achieve equilibrium by 10 hours. Protein concentrations and losses were higher with 2.6% glucose solution. Total protein and immunoglobulin losses per 24 hours were markedly lower than those reported for intermittent peritoneal dialysis. White blood cell counts increased slightly up to 5 hours and then remained constant up to 10 hours. Mononuclear cell counts were consistently higher than those of granulocytes. The efficiency of dialysis was not markedly influenced by uneven distribution of total exchange time. If 1.5% and 2.6% glucose solutions were used for particular time schedules, slightly higher dialysis efficiency could be obtained by using hyperosmolar solutions for the longer exchanges. Ultrafiltration volumes, protein and immunoglobulin losses, cell counts in dialyzate, and clearance of inulin varied among individual patients. Protein losses correlated positively with serum protein concentration and the body surface area of the patient. Clearances of insulin also correlated with body surface area but ultrafiltration volumes did not.

Clinical significance of histologic (Kiel) classification combined with immunologic definition of malignant lymphoma.

An actuarial survival (Kaplan and Meier) and complete remission (CR) rate were studied in 106 patients with malignant lymphoma (ML) in whom the histologic diagnosis (Kiel) was combined with the results of immunologic and cytochemical definition of tumor cells. There were 62 low grade (LG) and 44 high grade (HG) ML. Non-B cell malignancies constituted 42% of LG and 29.5% of HG tumors. Prognosis appeared to be related to the histological grade of malignancy and--only within the HG ML group--to the immunologic characteristics of tumor cells. The probability of 3-year survival of patients with HG B cell malignancies was 42%, with U cell tumors 25% and with T cell ML 11%. CR rate was 42% in B cell and 23% in non B cell HG ML. Immunological typing appears to be especially important in HG ML.

Hematocrit influence on peritoneal dialysis effectiveness during recombinant human erythropoietin treatment in patients with chronic renal failure.

Seven intermittent peritoneal dialysis (IPD) patients were investigated before and after correction of anemia with recombinant human erythropoietin (r-HuEPO). When hematocrit exceeded 30%, the peritoneal equilibration test was performed at 1, 2, 4, 8 hours. Correction of anemia was associated with a mean value increment in creatinine and phosphate clearance in 1- and 2-hour dwells. Differences in clearance of sodium, potassium, and urea in protein loss and glucose absorption before and after r-HuEPO therapy were not statistically significant. Increased creatinine and phosphate clearance during short dwells can be effected in IPD patients.

Effect of vitamin E modified cellulose membrane on human lymphocyte, monocyte, and granulocyte CD11b/CD18 adhesion molecule expression during hemodialysis.

Chronic renal failure induces a clinical state of immunodefi ciency that also depends upon a wide spectrum of dialysis membranes used during hemodialysis. Previous studies have shown that cellular immunodeficiency is caused by malfunc tion of the antigen presenting cells (monocytes or granulocytes). Subsequent activation of rolling mononuclear leuko cytes results in up-regulated expression of CD11b/CD18 (Mac-1) on endothelial cells. It is postulated that a VitE coated dialysis membrane might minimize the membrane biocompatibility, thereby generating a smaller amount of re active oxygen species (ROS). The purpose of this study was to evaluate the expression of the CD11b/CD18 adhesion mole cule on lymphocytes, monocytes, and granulocytes during HD in 10 patients, using flow cytometric analysis. The study protocol included the measurement of molecule expression using cellulose membrane (Clirans RS15, TERUMO Corp. Japan), and the same membrane coated by vitamin E (Exce brane, Clirans E15, TERUMO Corp., Japan) during 20 dialysi sessions each. Lymphocyte CD11 b/CD1 8 (Mac-1) expression did not change with either dialyzer type. However, monocyt (p = 0.046) and granulocyte (p = 0.018) CD11b/CD18 ex pression in the post HD period was significantly lower using the vitamin E coated membrane compared with the contro cellulose membrane. Our findings suggest a significant de crease in activation and migration of monocytes and granu locytes when using a vitamin E coated cellulose membrane.

Sympathetic activity response to changes in the intake of sodium in chronic renal failure.

Sympathetic response to differences in sodium intake in patients with chronic renal failure was investigated. All patients were on haemodialysis, first for 3 weeks with conventional dialysate containing 148 mEq/l of sodium, then for another 3 weeks with the conventional dialysate containing 131 mEq/l of sodium. Increase in noradrenaline (NA), adrenaline (A), dopamine (DA) concentrations and dopamine-beta-hydroxylase (DBH) activity were found during the high-sodium haemodialysis. However, DBH activity in patients was significantly lower than in healthy individuals. A significant correlation was found between the level of plasma NA and systolic blood pressure. The present results suggest that a higher intake of sodium causes dysfunction of the sympathetic system.

Noradrenaline turnover in the tissues of uraemic rats.

In female Wistar rats with acute renal failure a decrease of noradrenaline concentration in the heart, spleen and kidney was ascertained. Noradrenaline concentration after alpha-methyl-p-tyrosine and 6-hydroxydopamine in the heart, spleen and kidney was significantly lower than in the control group. In the adrenals a decrease of catecholamine level after alpha-methyl-p-tyrosine and 6-hydroxydopamine has been noted in the controls. The changes in tissue noradrenaline concentration are evidence of a dysfunction in the adrenergic nervous system in uraemic rats.

High and low sodium acetate haemodialysis and ultrafiltration. I. Comparison of haemodynamic effects.

This study was undertaken to evaluate the effect of increasing the dialysate sodium concentration on haemodynamic effects, arterial blood gases and chemistries during haemodialysis and ultrafiltration. Significant changes in mean blood pressure (MBP) and heart rate (HR) were not noted; but significant differences in sodium, potassium, total protein concentration, haematocrit and plasma osmolality during dialysis and ultrafiltration were found with both dialysates. Significant differences were also noted in pCO2 during dialysis and ultrafiltration with both dialysates and increase of pH during dialysis with low sodium dialysate. Significant changes in kind and frequency of unpleasant symptoms were found with both dialysates.

Sympathetic activity, plasma renin activity (PRA) and kininogen levels in patients haemodialysed with acetate and bicarbonate.

Sympathetic, renin and kinin responses to an acetic and bicarbonate fluid in haemodialysed patients were investigated. Increases in dopamine-beta-hydroxylase (DBH) activity, PRA and kininogen levels were found during single dialysis but there was no difference in acetate and bicarbonate haemodialysis. The present results suggest that changes in sympathetic renin and kinin activity were similar in patients treated with either acetate or bicarbonate fluid.

Leukopenia with different regenerated haemodialysis membranes.

The white blood cell count (WBC) decreases during haemodialysis and it was investigated as a function of different dialysis membranes. Each of them was used four times, applying different sterilization methods. Twelve chronic haemodialysis patients were studied and dialysed with cuprophan and polyacrylonitrile (PAN) membranes. Cuprophan was studied by a dry sterilization method and after perchloric acid and formalin treatment. PAN was studied with dry sterilization and after perchloric acid. As it has been shown, cuprophan membranes cause significantly more marked neutropenia than PAN. No significant difference was seen in pO2, pH, pCO2 and bicarbonate between dialysers used four times. The results indicate differences in biocompatibility between cuprophan and PAN membranes, independent of the sterilization method employed.

Some hormones, minerals and vitamin D in continuous ambulatory peritoneal dialysis.

The concentrations of insulin (IRI), parathormone (PTH), calcitonin (CT), some electrolytes (Ca, Mg, P), vitamin D and glucose were determined in 6 patients with terminal renal insufficiency treated by CAPD.

Influence of intraperitoneal vancomycin on peritoneal dialysis efficiency. A clinical study.

Peritonitis is a major complication of intermittent peritoneal dialysis (IPD); over 70% of the infections are caused by Gram-positive bacteria. Vancomycin (V) is the antibiotic of choice in the treatment of peritonitis caused by G(+). The influence of vancomycin on peritoneal transport in IPD patients has not been described before. We have investigated the effect of intraperitoneal vancomycin on dialysis efficiency in 8 IPD patients using dialysis solutions containing either lactate or acetate. The following parameters were measured: net ultrafiltration (UF), concentration ratios (D/P) of urea, creatinine, potassium, peritoneal clearances (ml/min) of urea, creatinine, potassium, mass transfer of sodium (MTNa), sodium sieving index (SCNa). It has been found that vancomycin significantly decreases D/P urea (p < 0.05) and creatinine (p < 0.05). We found also a significant decrease of mean clearance of urea (p < 0.05) and creatinine (p < 0.05). The mean clearance of potassium did not change significantly. There was no significant change in UF, MTNa, and SCNa. Our preliminary data suggest that vancomycin decreases the permeability of peritoneum for certain low molecules in IPD patients which may have a negative impact on dialysis efficiency.

Relationship between some prognostic markers of HD patients and serum erythropoietin, insulin-like growth factor-1, leptin, parathormone and testosterone.

Iseki et al. [1] have shown that serum levels of albumin (Alb), creatinine (Cr) and BMI are significant predictors of death in haemodialyzed patients (HD pts). In our study we decided to assess the relationship between the levels of Alb, Cr, BMI and substances which have a known metabolic effect on nutritional status in HD pts: endogenous erythropoietin (Epo), insulin-like growth factor-1 (IGF-1), leptin (Lep), parathormone (PTH), and testosterone. The study was conducted in 53 (28M, 25F) stable HD pts. Serum levels of endogenous Epo and PTH were estimated by CLIA; IGF-1, Lep, testosterone, sex hormone binding globulin were estimated by RIA. The multiple regression analysis was done between Alb, Cr, BMI and Epo, IGF-1, PTH and Lep for all HD pts together and free androgen index (FAI) for men and women separately. Correlations: the level of serum albumin did not correlate significantly with any of the measured substances. Serum creatinine level significantly correlated only with the level of IGF-1 (p=0.02), BMI was significantly correlated with serum endogenous Epo (p<0.01), leptin (p=0.004) and FAI (p<0.005) both in men and women. We concluded that the higher concentrations of endogenous Epo, IGF-1 and testosterone could be correlated with a better prognosis in HD patients.

Plasma erythropoietin level and iron reserves in haemodialysis patients with and without acquired cystic kidney disease.

Concentration of erythropoietin (Epo) and iron reserves (IR) belong to the essential factors determining erythropoiesis in haemodialysis patients. Patients on dialysis with acquired kidney disease (ACKD+) can control anaemia better than patients without acquired kidney disease (ACKD-). Therefore we decided to check if plasma Epo levels and IR differ significantly in both groups of patients. Forty chronically haemodialyzed patients after ultrasound diagnosis were divided into 18 patients (45%) with ACKD+ and 22 (55%) without ACKD-. In both groups of patients we compared their plasma levels of Epo and IR. Plasma erythropoietin and ferritin levels were measured by enzymatic immunoassay. Iron reserves were estimated by the formula: IR = 400 x [ln (ferritin)-ln (50)]. In the ACKD+ group 72% of patients and in the ACKD- group 32% of patients did not require rHu Epo therapy. Plasma levels of erythropoietin and iron reserves did not differ significantly between ACKD+ and ACKD- patients. There must be also other factors than erythropoietin levels and iron reserves regulating erythropoiesis in these patients.

Phagocytic activity of polymorphonuclear leukocytes during haemodialysis in relation to some immunological findings.

The present study demonstrated prolonged decreases of phagocytic activity by neutrophils in comparison to transitory neutropenias during haemodialysis with cuprophane membranes, remaining in connection with non-equalization immunological findings as C3 complement levels, circulating immune complexes and lysozyme activity at the end of haemodialysis.