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Biomedical subjects

A Engeset

Publications and source records attributed to A Engeset.

At least 19 recordsLinked to original sources

Immune cells in peripheral lymph and skin of patients with obstructive lymphedema.

Lymph stasis in the extremities caused by interruption of lymphatics or insufficient lymph propulsion is often complicated by recurrent skin infections. To shed further light on this subject, we studied the phenotypical and functional characteristics of cells in peripheral lymph and skin of patients with obstructive lymphedema. Compared with controls, patients with secondary lymphedema displayed a high concentration of lymphocytes and erythrocytes in peripheral lymph, sometimes increased numbers of B cells, increased density of Langerhans cells in the epidermis and occasionally in the skin papillary layer, strong expression of class II antigens on skin endothelial cells and mononuclear infiltration around blood vessels, and margination of granulocytes in skin blood vessels. Reactivity of lymph cells to mitogens was augmented. Taken together these findings indicate that ongoing chronic inflammatory processes persist in skin with lymph stasis, and, moreover, with impaired lymphocyte and Langerhans cell trafficking from skin to regional lymph nodes and inefficient clearance of foreign antigens, these lymphedematous limbs become susceptible to infection.

Antibodies, Monoclonal

Effect of local hyperthermia on lymph immune cells and lymphokines of normal human skin.

The effects of 3 h lasting local hyperthermia on immune cell traffic through the normal human skin to afferent lymphatics, cell phenotypes, responsiveness, and stimulatory properties were studied in eight men. Cells were harvested from lymph drained from foot skin. Heating the skin in a water bath of 44 degrees C (skin temperature 2 mm under the surface 39 degrees C) evoked an augmented traffic of mononuclear cells to lymph with preponderance of large, macrophage-like, Ia-positive cells, among them Langerhans cells. Lymphocytes obtained from the heated skin lymph revealed in cultured increased spontaneous blastic transformation rate, augmented responsiveness to phytohemagglutinin (PHA), and enhanced PHA-presenting properties to autologous peripheral blood mononuclear (PBM) cells. An increased stimulatory activity on allogeneic mixed lymphocyte reaction (MLR) was also observed. Lymph from heated skin augmented the PBM responsiveness to PHA and showed increased interleukin-1-like activity. Local heating of the skin is a potent signal initiating augmented traffic, and enhanced responsiveness and stimulatory activity of "passenger" immune cells. Their rapid nonspecific activation makes them indiscriminately active against a wide range of antigens before the specific response is developed.

Adult

Influence of surgery on the responsiveness of blood lymphocytes in patients with advanced cancer.

The effect of surgery on peripheral blood mononuclear cell responsiveness to mitogens and suppressor cell (SC) activity assessed in a concanavalin A (ConA) assay were studied in patients with stage 0 and stage III-IV cancer. Patients were exposed to a similar surgical trauma the same type of anaesthesia, and to no pre- and early postoperative radio- or chemotherapy. A more pronounced postoperative decrease in the lymphocyte count, responsiveness to phytohemagglutinin (PHA) and ConA, and in the SC activity was found in the nonadvanced than advanced cancer group. These findings point to an impaired mobilization and distribution capacity of circulating lymphocytes in patients with advanced neoplastic disease.

Adenocarcinoma

Identification of interleukin-1 in normal human lymph derived from skin.

Interleukin 1 was isolated from human lymph drained from normal skin. The lymph was separated by gel filtration chromatography on Spherogel TSK SW 2000 column. IL-1 activity was found in three fractions: greater than 70 kD, 13-16 kD and 5-5.5 kD. Additionally a slight IL-1 activity was found in the 36-40 kD fraction. When exogenous IL-1 was added to the lymph inhibitory activity was detected in fractions: greater than 70 kD, 22-30 kD and 5.5-8 kD.

Adolescent

Epidermal cell thymocyte activity factor/interleukin 1 (ETAF/IL)-like activity in lymph drained from normal human skin.

Lymph derived from human skin contains lymphocytes which have a high rate of spontaneous blastic transformation in culture and are highly responsive to lectins. This phenomenon suggests that either a subpopulation of highly responsive lymphocytes is extravasated into skin, or skin tissue fluid and lymph contain humoral factors co-stimulating lymphocytes upon contact with tissue antigens. We sought to determine whether human prenodal lymph drained from normal leg skin possesses lymphokine activity. Significant augmentation of lectin induced thymocyte and autologous blood lymphocyte proliferation was produced by lymph. The augmenting activity was abrogated by incubation of lymph with anti-IL-1 antiserum. Supernatant from cultured lymph cells (lymphocytes, Langerhans cells) did not augment either thymocyte or autologous blood lymphocyte proliferation. No interleukin 2 activity was found in lymph. The data indicate that skin lymph possesses epidermal cell thymocyte activating factor/interleukin (ETAF/IL) 1-like activity which is not found in serum and that the main source of the putative lymphokine is epidermal and not migrating lymph mononuclear cells.

Adolescent

The effect of pretreatment with thio-TEPA and cytosine arabinoside on megakaryocytopoiesis in rats given a sublethal dose of thio-TEPA.

The present study was performed on rats, mainly to examine the so-called priming effect on megakaryocytopoiesis. One group of animals received 2 or 4 mg thio-TEPA or 200 mg cytosine arabinoside/kg body weight (the pretreatment) 2.5 days or 8 days prior to a dose of 10 mg thio-TEPA/kg body weight (the challenge dose). Another group received a pretreatment dose of 1 mg melphalan/kg body weight 2.5 days prior to a challenge dose of 3 mg melphalan/kg body weight. The number of bone marrow megakaryocytes, blood platelet production, mean platelet volume, blood platelet counts, leucocyte and granulocyte counts were examined on days 2, 4, 7, 10, 13, 16 and 20 after the challenge dose. The gut mucosa (number of mucosal crypts in terminal jejunum) and survival were studied in animals receiving pretreatment 2.5 days prior to a challenge dose of about LD100 for thio-TEPA and melphalan. No systematic differences were observed whether the animals received pretreatment prior to the challenge dose or not. Thus, no priming effect was observed.

Animals

Penetration to peripheral human lymph of clavulanic acid and ticarcillin.

An intravenous dose of 3.0 g ticarcillin and 0.2 g clavulanic acid was given to 11 healthy human volunteers in whom peripheral lymph, serum and urine were monitored for 8 h. The concentrations were assayed microbiologically. The mean levels in lymph collected during the period 0-1 h was 39.3 mg/l of ticarcillin and 2.93 mg/l of clavulanic acid. The mean peak concentration in lymph (appearing between 1.25 and 2.25 h) was 66.3 mg/l for ticarcillin and 4.1 mg/l for clavulanic acid. Elimination was slightly slower from lymph than from serum, the half-life being only 1.04 times longer from lymph than from serum for ticarcillin, but 1.22 times longer for clavulanic acid. The total areas under the concentration curves in lymph was 58% of the serum value of ticarcillin and 81.0% of clavulanic acid. This reflects the ability of the substances to penetrate to lymph. The mean 8-h urinary recovery was 63.7% of the dose of ticarcillin and 43.8% of clavulanic acid. The total body clearances were 14.61/h for ticarcillin and 7.91/h for clavulanic acid and the corresponding d beta distribution volumes 12.21 and 19.11. The ratio of the concentrations of ticarcillin to clavulanic acid in all body fluids increased with time. Pharmacokinetically, clavulanic acid is well suited to be given together with ticarcillin.

Adult

Glycogen content and PAS staining pattern of human megakaryocytes.

The glycogen content of human megakaryocytes was studied using a quantitative method. Smears of bone marrow from 13 individuals were stained with the modified PAS reaction with and without prior treatment with alpha-amylase. The intensity of the reaction was determined by microspectrophotometry in 50 megakaryocytes from each individual. It was found that megakaryocytes are rich in glycogen which is not only confined to the intensely PAS-positive granules and inclusion bodies, but also makes up a good part of the diffuse cytoplasmic staining. In the diffusely stained megakaryocytes, glycogen makes up 32% of the intensity of the PAS reaction, while it reaches 47% in those with granules and up to 60% in those with inclusion bodies. The total extinction of the PAS-stained megakaryocytes is not only dependent on the morphological appearances of the cells, but is also positively correlated with their size.

Bone Marrow Examination

Extravascular penetration of highly protein-bound flucloxacillin.

The pharmacokinetics of intravenously administered flucloxacillin (2.0 g to five volunteers) are described. The passage of flucloxacillin to peripheral lymph and suction skin blisters was monitored. This drug was selected because the high serum protein binding of 96% offered a particularly good opportunity for the study of the impact on tissue penetration. Flucloxacillin was assayed by high-pressure liquid chromatography, and pharmacokinetics were assayed by computerized curve fitting to accepted models. Penetration of flucloxacillin to extravascular foci was rapid. After 30 min the drug concentrations were 0.5 +/- 0.3 microgram/ml in lymph and 0.9 +/- 0.7 microgram/ml in blister fluid. The peak concentration was 11.7 +/- 5.6 micrograms/ml in lymph and 4.6 +/- 1.4 micrograms/ml in blister fluid. Concentrations in urine were above 111 +/- 50 micrograms/ml throughout the 8-h monitoring period, and urinary recovery was 60.4%. The half-life was 2.1 +/- 0.9 h in serum, 1.4 +/- 0.6 h in lymph, and 11.0 +/- 4.1 h in blister fluid. The differences in half-life were significant (P less than 0.05) between serum and blister fluid but not between lymph and serum. Penetration, as represented by the mean ratios of areas under the curve, was 19.7 +/- 8.1% to lymph and 38.2 +/- 11.7% to blister fluid. The flucloxacillin distribution volume during the phase of elimination was 36.4 +/- 16.0 liters and the total body clearance was 12.9 +/- 5.5 liters. Flucloxacillin showed good tissue penetration, considering its very high serum protein binding. High flucloxacillin levels in lymph and blister fluid were explained in part by drug affinity to extravascular albumin. The major impacts of high protein binding are (i) slightly slower passage into extravascular sites, (ii) slightly later peak concentration, and (iii) levels in extravascular fluid that are persistently below those in serum.

Adult

Pharmacokinetics of oral co-trimazine and the penetration of its components sulfadiazine and trimethoprim into peripheral human lymph.

Five healthy informed male volunteers received oral doses of 820 mg sulfadiazine (SDZ) plus 180 mg trimethoprim (TMP) (co-trimazine) every 24 h. Concentrations in serum, peripheral lymph from the leg and urine were determined after the first dose, and on the 4th day to reflect approximate steady-state conditions. TMP was assayed microbiologically and unchanged SDZ by high-pressure liquid chromatography. There was a rise in concentrations from the first dose to the 4th day. The rise for SDZ was by a factor of 1.6 in both serum and lymph; the rise for TMP was also 1.6 in serum, but 1.5 in lymph. The peak concentrations at steady state were 27.7 mg/l (SD) +/- 4.3 SDZ, and 1.6 +/- 0.68 mg/l TMP. The serum values at that time were 31.7 +/- 5.8 mg/l SDZ and 2.3 +/- 0.51 mg/l TMP. The simultaneous concentrations of both SDZ and TMP were always somewhat lower in lymph than in serum, also at the end of the observation periods, i.e. 12 h after the first dose and 72 h after the final one. But the serum concentrations of both SDZ and TMP were only slightly higher than in lymph. After the final dose, the ratio between the 12-hour areas under the concentration curves of lymph and serum was 0.68 +/- 0.12 for SDZ and 0.59 +/- 0.14 for TMP. The values after the first dose were similar, 0.63 +/- 0.17 and 0.57 +/- 0.05, respectively. The elimination half-life in serum during steady state was 16.5 h for SDZ, 8.6 h for acetylated SDZ and 9.4 h for TMP. In lymph the corresponding values were 19.2, 19.2 and 8.9 h.

Adult

Lymphatic drainage from subcutaneous tissue in the foot and leg in the sitting human.

To determine how fast lymph is drained from the foot in the sitting, completely relaxed position, we injected 99mTc-labelled human serum albumin subcutaneously between the first and second toe of both feet in three subjects sitting with legs down. Radioactivity appeared in the calf within the first 30 s, in the thigh within 1 min and in the blood between 2 and 5 min after injection. A scintigram of the calves showed distinct strands of activity. Radioactivity was found in the inguinal lymph nodes and in no other lymph nodes. The radioactivity in the segments of the calf showed rhythmic variations. EMGs showed minimal muscular activity during the examination. We conclude that interstitial fluid is drained by way of the lymphatics against gravity and most probably as a result of the intrinsic contractions of the lymphatics.

Adult

Temocillin penetration of peripheral lymph.

An intravenous dose of temocillin 1g was administered to 5 healthy human volunteers from whom peripheral lymph, serum and urine were monitored for 12 hours. The concentrations after 1 hour were 14.3 mg/L in lymph and 58.1 mg/L in serum. The mean peak concentration in lymph (appearing between 1.5 and 2 hours) was 30.6 mg/L, and the simultaneous serum level was 47.8 mg/L. The lymph concentrations were always below those in serum, and the elimination half-life was 4.4 hours from lymph compared with 4.9 hours from serum. The ratio between the total areas under the concentration curves in lymph and in serum was 0.56, which reflects the ability of temocillin to penetrate to lymph. Serum protein binding appeared to impede the rate of transport from serum to lymph, but when compared with the results of less highly bound penicillins the total penetration of temocillin was better than expected.

Adult

Decreased suppressor cell activity after surgery.

The effect of surgery on suppressor cell (SC) activity assessed in a ConA assay and concentration of OKT8+ cells in peripheral blood were studied in 16 patients with stage 0 cancer of uterus. An evident decrease in the number of freshly obtained OKT8+ and cultured for 20 hr with ConA OKT8+ cells and subsequently a drop in whole blood suppressor activity were found in the immediate postoperative period. The recovery of SC activity but not of OKT8+ cell level was observed on day 5. A nonsignificant decrease in E-RFC suppressor activity compared with that of whole blood SC suggests that function of T-suppressors has not been affected. The non-T cells did not produce any suppressive effect. These results indicate that the postoperative drop in the blood SC activity is due to the temporary depletion and not to the depressed function of SC.

Adult

Incidence of 'dry tap' on bone marrow aspirations in lymphomas and carcinomas. Diagnostic value of the small material in the needle.

Of 2907 bone marrow aspirations in patients with various malignancies, 192 or 6.6% exhibited 'dry tap'. In about 80% of the 'dry tap' there was material present inside the bone marrow needle which gave smears useful for evaluation of the bone marrow cytology. About 23% displayed normal cytology. Bone marrow involvement could be diagnosed in 13 out of 55 'dry tap' in Hodgkin's disease, 41 out of 46 in chronic lymphocytic leukaemia and lymphosarcoma, 6 out of 20 in reticulum cell sarcoma, 6 out of 9 in myelomatosis and 20 out of 45 in carcinoma. In a material of 174 aspirations with tumour cells in the bone marrow aspirate, the highest incidence of 'dry tap' was found in patients with Hodgkin's disease and patients with carcinoma, the lowest incidence in patients with multiple myeloma.

Biopsy, Needle

Time of exchange of 131I-labeled albumin between plasma and peripheral lymph in man.

The passage from blood to peripheral lymph of 131I-labeled human serum albumin has been studied in 6 male patients (30-70 years) with malignancies without metastases. On the first day the concentration of radio-labeled albumin in the blood was kept almost constant by repeated i.v. injections. Lymph was collected continuously from a cannulated subcutaneous lymph vessel on the leg. Two hours after the first i.v. injection of radiolabeled albumin the lymph contained significant amounts of radioactivity in all patients. Equilibrium between radioactivity in blood and lymph was reached after 26 hrs. This indicates a long "wash out time" of unlabeled protein in the interstitial tissue from where lymph has been sampled.

Adult