Leukocyte filtration does not affect lymphocyte subpopulations and NK cell function in recipients of blood transfusions.

BACKGROUND AND OBJECTIVES: The possible immunosuppressive action of blood transfusion has aroused great interest recently, particularly with respect to its effects on tumor growth and recurrence rate of malignant disease. MATERIALS AND METHODS: The effect of blood transfusion on lymphocyte subpopulations and NK cell function preoperatively and 6 months postoperatively was studied in 129 patients treated with elective surgery for colorectal malignancy. Forty-two patients (33%) received blood transfusions, 21 of them randomly allocated to receive leukocyte-depleted blood products. Investigation was by means of conventional laboratory methods. RESULTS: In 21 patients receiving a median of 3 units of non-leukocyte-depleted blood products (NLD), a significant reduction in CD4+ lymphocytes (44% vs. 40%, p < 0.01) occurred. In contrast, no significant changes in CD4+ lymphocytes were observed in the 21 patients transfused with leukocyte-depleted blood products (LD). However, with respect to lymphocyte subpopulations and NK cell function, differences between the NLD and LD groups were not significant. There was a marginal decrease in HLA-DR+ lymphocytes in the NLD patients without a history of previous transfusion. CONCLUSIONS: There seems to be no major change in lymphocyte subpopulations and NK cell function 6 months after blood transfusion. Thus we cannot confirm our previous findings of a reduced number of CD20+ cells after blood transfusion.

Photopheresis in the red man or pre-Sézary syndrome.

BACKGROUND: The beneficial effect of extracorporeal photochemotherapy has clearly been established for patients with cutaneous T-cell lymphoma with Sézary's syndrome. But this treatment has not been used in the red man syndrome or pre-Sézary syndrome. Some of these patients do not respond sufficiently or do not tolerate other therapies. OBJECTIVE: The purpose of this open study was to evaluate the clinical efficacy of photopheresis in this group of patients. METHODS: Seven patients with the red man syndrome were treated on 2 consecutive days every 4 weeks for 6-22 months. Six had been on systemic steroids and 3 had also received retinoids without sufficient effects. All were initially treated with topical nitrogen mustard but no longer tolerated this treatment. RESULTS: All signs of erythroderma disappeared in 6 of the 7 patients. All systemic therapy could be discontinued in all but 2 patients. No side effects were observed. CONCLUSION: Photopheresis may be an effective alternative treatment for this group of patients, when other types of therapy have failed.

The effect of previous blood transfusion on lymphocyte subsets and natural killer cell function in patients with colorectal cancer.

To elucidate the possible influence of previous blood transfusion on immune functions, the transfusion history of 153 patients admitted to hospital for elective colorectal surgery was correlated with lymphocyte subsets and natural killer (NK) cell function. The subsets determined were CD2, CD3, CD4, CD8, CD16, CD20, CD56, CD57 and HLA-DR-positive. The NK cell function was determined by measuring the killing capacity against cFDA-labelled K562 target cells monitored via a flow-cytometer. We found that 42 patients (27%) had been transfused before surgery, of these 13 had been transfused less than 30 days before surgery and 29 (19%) transfused more than 30 days before (median 10 years, range 0.1-37 years). In transfused patients, we found a significantly reduced number of B lymphocytes (CD20; p = 0.01), a reduction in HLA-DR-positive cells (p = 0.02) and a just significant reduction of NK cell function in transfused compared to nontransfused patients. The reduction in NK cell function is marginal and the NK cell function is within normal range, and probably without clinical significance. Reduction in NK cell function has been described before, whereas the reduction in B cells has not been reported earlier. The results may suggest an impaired humoral immunity and a minor reduction in cellular immunity in patients following blood transfusion.

[Gel technique, a new sensitive method for the determination of erythrocyte antibodies. Advantages and disadvantages with introduction of a new method]. / Gelteknik, en ny sensitiv metode til påvisning af erytrocytantistof. Fordele og ulemper ved indførelse af ny metode.

A gel technique for the detection of red blood cell antibodies was evaluated for antibody screening. A total of 1872 samples were screened using both gel technique and the conventional serological method, and later 18,292 samples were analysed by the gel technique and results confirmed by conventional methods. In both methods, Anti Human Globulin technique and enzyme technique were applied. The gel system gave false-negative results in 0.2% and false-positive results in 0.9% of the samples. The gel system was more sensitive than conventional technique in the detection of antibodies of clinical importance and less sensitive in detecting antibodies with low incidence of haemolytic transfusion reactions and haemolytic disease of the newborn. The gel technique seems suitable for laboratories with equipment for automatic pipetting of samples and reagents.

[Characteristics of first-time blood donors and their motives. A prospective study among voluntary and unpaid blood donors]. / Karakteristik af førstegangsbloddonorer og tilgrundliggende motiver. En prospektiv undersøgelse blandt frivillige og ubetalte bloddonorer.

We performed a questionnaire study among 413 consecutive voluntary unpaid blood donors being bled for the first time. About 50% were aged below 26 years, 93% were employed or students, and 50% of the donors came from families with other blood donors. The motives to donate blood were investigated. As motives we found: altruistic and humanitarian reasons in about 98%, to obtain a greater well-being in about 60%, tradition at the place of employment or in the family about 35% each. The importance of blood tests taken in connection with the blood letting was analysed. We could not find any support for the hypothesis that blood donors in Denmark enroll as donors to be tested for HIV antibodies.

A subroutine for rounding of numbers. Program in BASIC and for programmable calculators.

The present programs were developed to compensate for the poor precision of some microcomputer-BASICs, and to avoid printing of the non-significant figures of a numerical result. The program will round any number to a user defined number of significant digits. The subroutine is well suited for statistical programs. It enables the programmer to control the precision and format of numerical output. The program is given in two versions, one in BASIC and one for the programmable calculator TI-59.

A standard microcytotoxicity technique for quantitative analysis of lymphocyte subsets. A comparison with indirect immunofluorescence, evaluated by microscopy or flow cytometry.

A standard complement-dependent microcytotoxicity (CDC) technique was used for quantitative analysis of T-lymphocyte subsets in human peripheral blood and the results compared to those obtained by indirect immunofluorescence microscopy and flow cytometry. The monoclonal antibodies OKT3, OKT4 and OKT8 were used in the CDC method for detection of total-T cells, T-helper and T-suppressor cells respectively. The CDC technique provided reproducible results (CV, 3-7%) correlating well with both immunofluorescence techniques. This observation was valid both for healthy persons (n = 21) and for patients (n = 10) with immunological disorders. The correct antibody dilution, correction for background and the use of eosin staining are considered critical for the usefulness of this technique. The method has several advantages: it is widely used for histocompatibility testing, only simple equipment is necessary, and the amount of monoclonal antibody required per test is small.

Rhesus immunization after Rh-incompatible kidney transplantation.

Rh-immunization of a male recipient was observed following the transplantation of two kidneys from Rh-pos donors. Immunosuppression consisted of azathioprine, prednisone and antilymphocyte globulin (1st transplantation) and cyclosporin A and prednisone (2nd transplantation). The immunization was probably caused by the residual blood in the cadaver kidneys. The use of cyclosporin A might increase the risk of Rh-immunization.

Platelet cryopreservation with glycerol, dextran, and mannitol: recovery of 5-hydroxytryptamine uptake and hypotonic stress response.

Human platelets were frozen in 0.5 M glycerol, 0.5 M glycerol + 3% Dextran T40, or 0.5 M glycerol + 5% mannitol. The recovery of active transport of 5-hydroxytryptamine (5-HT) and the hypotonic stress response after freezing were dependent on the rate of cooling: the optimum range of rates was between 12 and 23 degrees C/min. The numerical recovery of cells was independent of cooling rate, but freezing altered the cell-size distribution. The combination of dextran and glycerol was no better than glycerol alone at protecting platelets against freezing damage. Mannitol, however, adversely affected platelet 5-HT uptake, and this was reflected in a low recovery of that activity after freezing platelets in glycerol supplemented with mannitol.

Red cell 2,3-DPG, ATP, and mean cell volume in highly trained athletes. Effect of long-term submaximal exercise.

20 male elite long distance runners were compared to a control group of blood donors to determine the effect of training on red blood cells. The acute effects of exercise on red cells were investigated in 11 of the runners following a race of 15-30 km. The runners had elevated resting values of red cell 2,3-DPG (P less than 0.05) and mean cell volume (P less than 0.01); blood Hb and ATP were not different from concentrations in the control group. The red cell status of the athletes may be explained by an increased proportion of young erythrocytes in runners. No statistically significant changes in red cell 2,3-DPG, ATP, mean cell volume or blood Hb were found post exercise.

Hypothalamic-pituitary-gonadal function in relation to liver function in men with alcoholic cirrhosis.

Serum concentrations of oestrone, oestradiol, follicle-stimulating hormone (FSH), luteinizing hormone (LH), and sex hormone-binding globulin (SHBG) were significantly (P less than 0.01) raised in men with alcoholic liver cirrhosis (no. = 42) compared with age-matched controls (no. = 20). No significant difference was observed when comparing serum testosterone concentrations. Patients were divided into three groups in accordance with the severity of liver cirrhosis, using biochemical and clinical criteria. Patients with the best-preserved liver function (no. = 11) and patients with moderately affected liver function (no. = 18) had significantly (P less than 0.05) raised serum concentrations of testosterone, FSH, and LH when compared with both controls and patients with severely affected liver function (no. = 13). Serum concentrations of testosterone, FSH, and LH in the latter group showed no significant differences from the controls. Serum concentrations of oestrone and oestradiol were significantly (P less than 0.05) increased in all patient groups, and serum oestrone increased with decreasing liver function. No significant differences were observed concerning SHBG concentrations in the three groups of patients. Dexamethasone suppression did not change the concentration of testosterone significantly, but oestrone and oestradiol concentrations decreased significantly (P less than 0.01) in controls and patients. In patients, but not in controls, a significant (P less than 0.01) increase in FSH and LH concentrations was observed after dexamethasone suppression. The mean percentage increase of FSH and LH was higher the greater the severity of liver cirrhosis.

Oxyhaemoglobin equilibrium and chronic beta-adrenoceptor blockade in coronary heart disease.

In 20 patients with coronary heart disease the effect of long-term beta-adrenergic receptor blockade on the haemoglobin oxygen equilibrium was investigated. Study patients received alprenolol 200 mg twice daily for 12-41 months (mean: 24 months) as a secondary preventive measure following a myocardial infarction. While on and again following gradual withdrawal of alprenolol, the patients performed a maximum bicycle ergometer test. Haemoglobin oxygen affinity as expressed by the P50 value, 2,3-diphosphoglycerate (2,3-DPG) and carbon monoxide haemoglobin were measured before and following exercise. Pre-exercise P50 decreased from 25.2 +/- 0.3 mm Hg (mean +/- s.e. mean) while on beta-adrenoceptor blocker to 24.6 +/- 0.4 mm Hg in the off-treatment state (P less than 0.05). Five minutes after stopping exercise P50 was 25.1 +/- 0.3 in patients taking alprenolol as compared to 24.7 +/- 0.3 after withdrawal of the drug (P less than 0.01). It is concluded that the slight decrease in haemoglobin oxygen affinity in long-term treatment with alprenolol, which is observed in the present study probably is without clinical bearing. The question should be further elucidated by analysis of coronary sinus blood samples.

Oral testosterone load related to liver function in men with alcoholic liver cirrhosis.

The relation between liver function and an oral testosterone load was examined in 42 consecutive patients with alcoholic liver cirrhosis. Administration of an oral load of 400 mg micronized free testosterone increased the serum concentration of testosterone (range, 31.9-694.4 nmol/l; median, 140.8 nmol/l) in male patients with alcoholic liver cirrhosis to significantly (P less than 0.01) higher levels than in male subjects without liver disease (range, 25.4-106.6 nmol/l; median, 61.5 nmol/l). The increase of testosterone after the load (log delta testosterone) in patients correlated inversely with galactose elimination capacity (r = 0.54; P less than 0.001), serum albumin (r = -0.53; P less than 0.001), plasma factor II + VII + X (r = 0.62; P less than 0.001), indocyanine green clearance (r = -0.71; P less than 0.001), and hepatic blood flow (r = -0.61; P less than 0.01) and correlated directly with wedged-to-free hepatic vein pressure (r = +0.54; P less than 0.01). The increase of testosterone after the load did not correlate significantly with sex hormone-binding globulin (r = +0.35; P greater than 0.05). It is concluded that the hepatic extraction of testosterone is significantly decreased in patients with alcoholic cirrhosis. This decrease seems to be due to decreased liver function, decreasing hepatic blood flow, and increased portosystemic shunting. Oral testosterone loading may therefore be of prognostic significance in patients with alcoholic liver cirrhosis.

Platelet function and fibrinolytic activity following distance running.

6 long distance runners from the Danish marathon elite and 6 non-runners completed test runs of 28 and 12 km, respectively. Distance runners and non-runners showed the same responses in platelet function. We found a significant decrease in ADP induced platelet aggregability, a decreased serotonin release induced by ADP and collagen and an increase in platelet factor 4 immediately following the run. The antithrombin III levels remained constant. Euglobulin lysis time was shortened (by approximately 50%) and the plasminogen levels significantly increased. The last 2 findings indicate an equal increase in fibrinolytic activity during distance running in both groups. While short term, strenuous exercise induces platelet hyperaggregation, long term distance running induces a state of exhaustion of platelet aggregation capacity.

Coronary risk factors and plasma sex hormones.

Recent studies have reported higher plasma estradiol levels in male survivors of acute myocardial infarction. This finding has raised the possibility that hyperestrogenemia may consitiute a separate coronary risk factor. In 443 men, aged 30, 40, 50, and 60, we assessed the relationship between plasma levels of estradiol, testosterone, and testosterone-binding globulin and coronary risk factors: fasting plasma concentrations of triglyceride, cholesterol, and high-density lipoprotein, blood pressure, and smoking and leisure-time physical activity patterns. Plasma estradiol concentrations were found to correlate significantly with body weight. After adjustment for this association, we found that the mean plasma estradiol concentration still was significantly higher in smokers than in nonsmokers. No other correlation could be estabilished between plasma hormone levels and coronary risk factors. The relative hyperestrogenemia reported in men with previous myocardial infarction may be due to an effect of smoking but may also reflect the relationship between body weight and plasma estradiol levels. Future studies should consider the demonstrated association between plasma estrogen levels and smoking.

Muscle cell leakage due to long distance training.

Abnormal myoglobinemia (above 77 microgram/l) and free hemoglobin in plasma were found in 16 runners and in nine non runners immediately following distance running. The same abnormalities were found iun six elite rowers following rowing. In parallel with the rise in myoglobin and free hemoglobin a rise was found in serum concentrations of cellular enzymes (LDH, CK, ASAT, alkaline phosphatase) and of various metabolites. We found no proteinuria nor casts in the urine. Non runners had a higher rise in serum myoglobin than runners. Competitive running caused a rise in the serum concentration of the heart specific fraction of creatine kinase in seven of the nine (healthy) elite runners. The abnormal findings are only explainable on the basis of leakage of proteins from muscle cells to the circulation in otherwise healthy, well trained persons. Myoglobinemia and a transient rhabdomyolysis is a common phenomenon in long distance running, but evidently also occurs in distance rowing. Three months of running training prevented most of the muscle damage from relaxed jogging in the nine previous non runners. Neither the observed myoglobinemia nor the hemoglobinemia resulted in any significant loss of iron in the urine.

Pituitary-testicular function in patients with alcoholic cirrhosis of the liver.

In forty-two patients with alcoholic liver cirrhosis and without recent alcohol ingestion the pituitary-testicular function was studied in an effort to relate the endocrine abnormalities with the degree of liver cell dysfunction, evaluated on a quantitative basis. Compared with values in twenty-one healthy controls, we found significantly elevated serum oestrone, oestradiol, follicle-stimulating hormone, luteinizing hormone and prolactin (P less than 0.01). Serum dehydro-epiandrosterone and dehydroepiandrosterone sulphate were significantly reduced in the cirrhotics (P less than 0.01), whereas serum testosterone was not significantly different from that in the controls. Raised levels of sex-hormone binding globulin were found in 71% (22/31) of the patients (median 8 x 10(-18) mol/l, range 3-17 x 10(-8) mol/l). The incidence of gynaecomastia (38%), cutaneous spiders (67%), testicular atrophy (24%) and reduced axillary hair (71%) was without significant relation to raised levels of sex-hormone binding globulin or progressively reduced liver function. In the presence of clinical or hormonal hypo-gonadism we found evidence of a state of primary hypogonadism together with an inadequate secretion of gonadotropins. The state of hyperoestrogenaemia and the concentration of gonadotropins were significantly correlated to the hepatic synthesis of coagulation factors.