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Biomedical subjects

A Engeset

Publications and source records attributed to A Engeset.

At least 37 records · Page 2Linked to original sources

Penetration of antibiotics to tissues and infected foci.

There is proportionality between the area under the curve of concentrations in serum and the area under the curve in tissues and other extravascular foci of the body. A high peak area under the serum curve - PAUC - establishes high extravascular concentration levels in tissues, operation areas and infected sites. Most antibiotics are able to produce satisfactory antibacterial levels in interstitial tissue fluid regardless of serum protein binding. Binding to components of interstitial space, like alpha 1-globulin, inhibits the establishment of the concentrations. Administration of a prophylactic agent by infusion 1 h before an operation suffices to produce anti-bacterial levels in wound tissues to inhibit growth of susceptible bacteria contaminating it during the operation.

Anti-Bacterial Agents↗

The effect of surgery and chemotherapy on blood NK cell activity in patients with ovarian cancer.

The cytotoxic activity of NK cells in peripheral blood was studied in 15 patients with ovarian cancer Stage III and IV before and after surgery and ten-week intramuscular therapy with thiotepa. An evident decrease in NK activity was found 24 hours after surgery, with a slow return toward normal values within 7-9 days. No differences between patients with explorative laparotomy and with extirpation of the tumor were observed. The mechanism of the decreased NK cytotoxicity remains unknown but there was a concomitant reduction in the number of blood mononuclears. A second drop in NK activity occurred after chemotherapy. It was most likely due to the drug bone marrow depression. No evident correlation between the reduced NK activity and advancement of the disease could be found.

Adult↗

Rat liver contains a distinct blood-borne population of NK cells resistant to anti-asialo-GM1 antiserum.

A high level of anti-tumoral (NK) cytotoxicity was observed in the mononuclear population washed out from the liver microvasculature in rat. The level of cytotoxicity against K562 and YAC1 cells, percentage of large granular lymphocytes (LGL) and of OX8+ cells was significantly higher than in the inflowing portal and also caval blood. A low concentration of adherent, phagocytic and OX6+(Ia) cells and a higher level of cytotoxicity after removal of adherent cells ruled out the possibility of liver macrophages to be responsible for the cytotoxicity. Surprisingly, the liver-sequestered NK population turned to be resistant to anti-asialo-GM1 antiserum. Thus, liver microvasculature contains a significant number of cells with characteristics of NK cells which constitute a functionally distinct NK population.

Animals↗

Temocillin in peripheral lymph.

One gram of temocillin was given intravenously to five healthy volunteers to study the concentrations in serum and peripheral lymph obtained by cannulation of the lower leg. The 1 h serum level was 58.1 mg/l and the lymph level 14.3 mg/l. The mean peak lymph concentration was 30.6 mg/l and occurred between 1.5 and 2 h; the simultaneous serum level was 47.8 mg/l. The antibiotic levels in lymph were always below those in serum. The urinary recovery over 12 h was nearly 60%. The mean ratio between the areas under the concentration curves of lymph and serum was 0.558. The serum half-life was 4.9 h, the apparent beta-phase distribution volume 18.41. In comparison, the lymph half-life was 4.4 h. Protein binding appears to be of little consequence to the ability of temocillin to penetrate well into extravascular foci.

Adult↗

Distribution to human peripheral lymph of amoxycillin and of ampicillin from the oral prodrug bacampicillin.

Equivalent doses of 1600 mumol each of amoxycillin (582 mg) and ampicillin from bacampicillin (800 mg) were studied in five fasting healthy volunteers in a cross-over study. Peripheral lymph was collected from the legs by cannulation of subcutaneous lymph vessels. Antibiotic concentrations were determined by bioassay. Passage to the lymph was rapid; for both agents lymph peaks occurred between 1-2 h after serum maxima. The compounds showed similar ranges of serum and of lymph concentrations; the mean individual peak concentration, area under the concentration curves, and elimination half-life in serum were 9.6 mg/l, 24.8 mg.h/l, and 0.80 h respectively for amoxycillin and 11.0 mg/l, 21.4 mg.h/l, and 0.93 h for ampicillin from bacampicillin. In lymph, the corresponding values were 5.5 mg/l, 21.9 mg.h/l, and 1.1 h for amoxycillin and 4.7 mg/l, 16.1 mg/l, and 1.0 h for ampicillin. The ratios between concentrations in lymph and serum were similar. The ratios between the total areas under the concentration curves was 0.88 +/- 0.19 for amoxycillin compared to 0.80 +/- 0.10 for ampicillin from bacampicillin. The areas under the lymph concentration vs. time curves ranged from 69-107% of the serum curve values of amoxycillin and 71-97% for ampicillin. Both drugs persisted longer in lymph than in serum. This pattern was somewhat more pronounced for amoxycillin, probably because of its more sustained serum concentrations due to delayed absorption. Thus the two antibiotics were similar in respect to passage into peripheral lymph.

Adult↗

Prostatic acid phosphatase in serum and bone marrow in patients with prostatic carcinoma.

Sixty-two per cent of 61 patients with prostatic carcinoma showed elevated levels of serum acid phosphatase, analysed by radioimmunoassay (RIA). Enzymatically determined serum acid phosphatase was raised in only 38% of the same patients. Bone marrow acid phosphatase determined by RIA was raised in 41%. In untreated metastatic patients with prostatic carcinoma, radioimmunologically determined serum acid phosphatase was elevated in 12 of 13 patients, whereas bone marrow acid phosphatase (RIA) and enzymatically determined serum prostatic acid phosphatase were increased only in about half of the patients. In a control group the upper reference limit of bone marrow acid phosphatase determined by RIA was significantly raised above that obtained by serum analyses. This indicates that nonprostatic acid phosphatases (possibly from bone marrow cells) cross-react with prostatic acid phosphatase in an unpredictable way, even when using a specific radioimmunoassay. In patients with metastatic carcinoma of the prostate, the results of bone marrow acid phosphatase determinations, analysed by RIA, seem to lack diagnostic and/or prognostic information additional to that obtainable by serum acid phosphatase (RIA) analysis.

Acid Phosphatase↗

Suppressor cell activity in peripheral blood in cancer patients after surgery.

The influence of operative trauma on the responsiveness of PBM to PHA and Con A and the level of Con A-induced suppressor cell (Con A-SC) activity toward autologous responder cells (RC) were examined in patients with stage 0 uterine cancer after hysterectomy. The operation brought about a decrease on the second post-operative day in the responsiveness of PBM to various concentrations of PHA by 19.2-28.8% and to Con A by 31.2-41.8%, concomitantly with a decline in Con A-SC activity from 43.7 to 22.0%. When the Con A-SC were tested against RC obtained from blood samples drawn prior to surgery and stored at -196 degrees C, an increase in the post-operative SC activity from 41.6 to 52.2% was observed which might indicate a post-operative stimulation of SC. On the other hand, when Con A-SC were raised from PBM drawn before surgery and tested against RC obtained post-operatively, they displayed a decreasing suppressive activity from 27.2 to 2.7%. This might be due to the pre- and post-operative stimulation of RC. The observed changes were most likely caused by a transient decrease in the number of blood T lymphocytes, altered proportions of blood T cells to other PBM cells and probably a non-specific stimulation of autologous cells responding in the suppressor cell activity assay.

Adult↗

Low ploidy megakaryocytes in steady-state rat bone marrow.

The amount of DNA in individual megakaryocytes (MK) was measured by Feulgen photometry performed on smears of steady-state rat bone marrow. The MK were identified by acetylcholinesterase (ACHE) staining. The method described is particularly suitable in the study of immature MK, hitherto difficult to examine for DNA content. The main MK ploidies were 8N, 16N, and 32N, comprising 33.4% +/- 1.4%, 40.8% +/- 1.4%, and 17.9% +/- 1.3%, respectively, of the total MK numbers. Only 6.7% +/- 1.7% had less than octoploid DNA content. Very few cells were found belonging to the 64N class. Among the immature MK, a relatively large fraction was found between the ploidy levels, indicating a rapid turnover within these ploidy classes. The demonstration of ACHE activity even in MK with a diploid DNA content indicates that the flow from the committed progenitors to differentiated MK occurs at the 2N level.

Animals↗

High spontaneous and mitogen-induced activity of mononuclear cells in lymph draining normal human skin.

Lymphocytes in afferent lymph draining skin are derived from populations selected at the capillary level to enter the tissue space and which migrate spontaneously through the tissue to the initial lymphatics. These cells reveal a high spontaneous transformation rate in a 72 h culture. The mean 3H TdR incorporation was in a 24 h culture 2 times and in a 72 h culture 5 times higher than that of the peripheral blood mononuclear cells of the same subjects. The lymph cells responded significantly stronger to low concentrations of PHA, ConA and PWM than the blood cells. Also, the peak response of lymph cells was apparent at lower concentrations of mitogen in culture than of blood cells. The lymph cell population revealing a high spontaneous transformation rate was found to be the OKT4 enriched subset (induced/helper). The findings of a high spontaneous activation of lymphocytes which trafficked through the normal skin and defining this highly reactive subset as an OKT4-positive and strongly responsive to mitogens, reflect the in vivo immune events in the normal skin.

Adolescent↗

Natural killer lymphocytes in rat liver sinusoidal blood.

Blood-borne cells with the characteristics described for the natural killer (NK) lymphocytes were recovered from the liver sinusoids in rat. They had cytotoxic activity against K 562 cells in a 18 h 51Cr release assay, target binding rate and large granular lymphocytes percentage higher than the inflowing portal blood cells. The cytotoxic effector population was non-adherent and peroxidase negative, enriched in cells with Fc- and C36-receptors. Deprivation of liver of portal or mesenteric blood supply significantly decreased the liver NK activity not affecting the level of cytotoxicity in the portal blood. Splenectomy produced only a moderate decrease of activity. These findings may indicate that liver sinusoids is the site of accumulation of blood-born NK cells or of maturation of the NK-precursors. One possible mechanism by which natural cytotoxicity controls tumor growth and spread might be the killing of circulating tumor cells arrested in the liver by the blood-born NK-cells.

Animals↗

Serum ferritin and bone marrow haemosiderin in patients with malignancies and in healthy controls.

Serum ferritin has been analysed and bone marrow haemosiderin evaluated in 306 patients with malignancies, mostly lymphomas, and in 46 healthy controls. Also haemoglobin, serum iron, transferrin and liver enzymes were analysed simultaneously. 60% of the patients had serum ferritin above normal values and 20% had values above 1000 micrograms/l. There was a good correlation between serum ferritin and bone marrow iron both in the patients and in the controls, r = 0.67 and r = 0.77, respectively. There was a negative correlation between serum ferritin and haemoglobin concentration in the patients and a positive correlation in the controls. In patients with Hodgkin's disease serum ferritin was related to the stage of the disease.

Bone Marrow↗

Cells in lymph draining normal human skin-monoclonal antibody analysis.

The immune cells which migrate into the human skin from the blood and subsequently leave it via lymph vessels play an important role in immune processes. We made use of the monoclonal antibodies, characterizing cell populations which migrate into the normal skin and which having traversed the tissue, could be recovered from the afferent lymph vessels. The percentage of OKM1+ cells (monocytes/macrophages, null cells) in lymph was low (8.9 +/- 1.6%) when compared to that of blood (16.5 +/- 4.6%) (p less than 0.05). The OKM1 antibody labeled only 40% of the large macrophage-like lymph cells. The percentage of OKT3+ (T cells) in lymph was higher (75.4 +/- 4.0%) than in blood (54.0 +/- 4.5%) (p less than 0.05) as was that of the OKT4+ (inducer/helper) subset (41.5 +/- 9.5 and 33.3 +/- 4.8%, p less than 0.05), while cells of the OKT8+ (suppressor/cytotoxic) subset were found to be less numerous in lymph than in blood. (18.4 +/- 6.2% and 20.3 +/- 4.9%, p less than 0.05). The OKI a1+ cell population consisted of large veiled macrophage-like cells and only very few small cells. Around 60% of the large mononuclear cells present in lymph reacted with OKT6 antibody specific for cortical thymocytes. The finding of high proportions of T cells, cells bearing la-like antigens, and a high inducer/suppressor ratio in normal prenodal lymph reflects the intensity of "physiological" immune processes in the normal skin.

Adolescent↗

High-sensitivity optical lymph flow-meter.

An optical flow-meter is described which allows precise and continuous registration of the flow of lymph from cannulated human lymph vessels. The cannula from the lymph vessel is connected to the measurement tubing of the instrument where the flow is measured by automatically monitoring the movement of an air bubble introduced into the flow at the beginning of the measurement. The limit of sensitivity of the instrument is about 0.1 microliter, allowing reliable registration of stroke volumes of about 1 microliter which typically occur in human leg lymphatics. The size and capacity of the instrument were chosen to be suitable for clinical use. A technical description of the instrument is given. Application of the instrument is illustrated with recording of lymph flow and lateral intralymphatic pressure in a prenodal lymph vessel of the human leg.

Lymph↗

C1 inactivator and C3b inactivator in peripheral lymph of normal men.

The concentrations of C1 inactivator and C3b inactivator were measured in the peripheral lymph of leg of normal men and compared with the concentrations in serum. Both inactivators were found in lymph, however, in concentrations lower than in serum (lymph/serum ratio for C1INA 0.236, for C3bINA 0.238). The levels of C1INA proteins in lymph were higher than of C1q and C1s (p less than 0.05), and of C3bINA higher or equal to those of C3 and C3PA. This may indicate, that the relatively high concentrations of both inactivators in the extravascular space, as compared with complement component proteins, can play a role in the control of activation process of complement in the interstitium and also explain to some extent the observed low hemolytic activity of lymph C1 and C3.

Adolescent↗