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Biomedical subjects

K Abraham

Publications and source records attributed to K Abraham.

At least 19 recordsLinked to original sources

[Non-invasive detection of left ventricular diastolic function in variously trained endurance athletes during a marathon run with pulsed Doppler sonography].

UNLABELLED: To evaluate left ventricular (LV) diastolic function in long distance runners LV filling parameters were assessed by Doppler echocardiography during marathon race in 23 male subjects. On the basis of their personal record the athletes were divided into two groups: 12 endurance athletes (END; 218 min over 42 km) aged 34 years (29/37, median and 25%/75%-percentiles) and 11 ultra endurance athletes (ULTRA; 152 min over 42 km) aged 32 years (28/37). At rest 21 healthy untrained subjects (UT) aged 33 years (28/37) served as control group. In long distance runners the values for LV mass and LV mass index were significantly higher in END with 210 (168/253) g rsp. 110 (87/135) g/m2 and in ULTRA with 225 (179/267) g rsp. 118 (93/142) g/m2 as compared to UT with 129 (105/162) g rsp. 68 (57/79) g/m2 (p less than 0.001 each). Doppler-derived mitral flow was characterized by the early passive (E wave) and late (A wave) diastolic inflow. In particular atrial filling fraction (AFF) as the relative atrial contribution to LV filling was measured. At rest and at km 21 we saw a normal filling behaviour (AFF = 27% bzw. 28%) in both groups of long distance runners with an AFF of 27 (26/29)% in END and an AFF of 28 (26/29) in ULTRA. In END AFF rose to 42 (38/47)% at km 42 (p less than 0.001) and remained significantly elevated with 37 (35/42)% until 30 min post marathon (p less than 0.05). Only 60 min post exercise AFF returned to baseline values with an AFF of 28 (25/39)% in END. In contrast at km 42 in ULTRA AFF was significantly lower and at baseline levels with 26 (25/29)% compared to END (p less than 0.001) and did not significantly change in the further course of the post running period. CONCLUSION: Long distance runners show a normal LV filling behaviour at rest despite significant LV hypertrophy. In contrast to top class athletes (ULTRA) there is a shift of LV filling from early (E wave) to late (A wave) diastole in less trained runners (END) during marathon. Thus, the results indicate an impairment of early diastolic LV filling in amateur endurance athletes (END) during extreme physical exercise.

Adult

Persistence of various polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDDs and PCDFs) in hepatic and adipose tissue of marmoset monkeys.

A defined mixture of polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDDs and PCDFs) was subcutaneously administered to marmoset monkeys (Callithrix jacchus). Tissue concentrations in hepatic and adipose tissue were measured at different times after treatment (1-28 weeks). One week after application high concentrations could be detected for the 2,3,7,8-substituted congeners only. The percent of the administered dose in whole liver differed for the various 2,3,7,8-substituted congeners, ranging from 24.5 +/- 4.5% for 2,3,7,8-TCDD to 74.1 +/- 4.9% for 2,3,4,6,7,8-H6CDF. Therefore, the concentration ratio (liver/adipose tissue) was also very different, ranging from about 1 (2,3,7,8-T4CDD or 2,3,7,8-T4CDF) to greater than 10 in the case of some higher chlorinated PCDDs and PCDFs. Half-lives of PCDDs and PCDFs were very different for the various 2,3,7,8-substituted congeners. For the most toxic compound (2,3,7,8-T4CDD) a t/2 of about 8 weeks in hepatic tissue and about 11 weeks in adipose tissue was found when calculated from data obtained later than 6 weeks after injection. For 2,3,7,8-T4CDD and 1,2,3,7,8-P5CDD the decreases in hepatic concentrations were much faster during the first 6 weeks after administration (t/2 of 4 weeks). This was apparently due to redistribution phenomena. Half-life increased with increasing degrees of chlorination. In some cases (e.g. OCDD, OCDF) no significant decrease in tissue concentrations could be observed after 28 weeks. The shortest t/2 was determined for 2,3,7,8-T4CDF: shorter than 6 days in hepatic tissue and about 10 days in adipose tissue. Calculation of the body burden of the non-2,3,7,8-substituted PCDDs/PCDFs 1 week after injection revealed that all groups of isomers were present at less than 5%. Consequences of these findings for the use of TCDD-toxic-equivalency factors are discussed and a change in strategy is suggested.

Absorption

Synchronous adenocarcinomas of jejunum and cecum following transverse colon carcinoma. A case study.

A case of synchronous primary adenocarcinomas of the small and large bowel in a patient previously treated by transverse colectomy for cancerous polyps is presented. These new primaries were incidental findings during surgery for suspected recurrence of colonic carcinoma. Primary tumors of the small bowel are rare, and the diagnosis of primary adenocarcinoma of small bowel in the presence of primary adenocarcinoma of large bowel requires a high degree of suspicion and may well modify the prognostic outcome if detected early.

Adenocarcinoma

Anti-laminin receptor antibody targeting of liposomes with encapsulated doxorubicin to human breast cancer cells in vitro.

The tumor cell laminin receptor is a cell-surface protein that binds laminin with high affinity (Kd = 1.0 nM). The putative ligand-binding domain of the laminin receptor has been molecularly cloned and sequenced. In the present study, we used the predicted amino acid sequence of the laminin receptor to generate synthetic peptide antigens and produced immunoglobulin M (IgM) anti-laminin receptor monoclonal antibodies. The disulfide bond group of the IgM molecule was used to couple the antibodies to the surface of liposomes encapsulating doxorubicin. The anti-laminin receptor monoclonal antibodies coupled to the liposomes bound avidly to the surface of MDA-MB-435S (MDA-435) human breast carcinoma cells, which have high numbers of laminin receptors. These antibody-coupled liposomes exhibited a low degree of binding to Hs 578Bst (Hs 578) normal human breast epithelial cells, which express a low number of laminin receptors. Excess liposomes competed for the binding of unbound laminin to the tumor cell surface, and excess laminin competed for binding with the liposomes. Antibody-coupled liposomes encapsulating doxorubicin were specifically more efficient in inhibiting colony formation by MDA-435 cells in vitro than unbound doxorubicin or liposomes without anti-laminin receptor monoclonal antibodies. Unbound doxorubicin inhibited thymidine uptake by 10%-20% in both Hs 578 and MDA-435 cells, whereas the antibody-coupled liposomes encapsulating doxorubicin inhibited thymidine uptake by 90% in MDA-435 cells but only 15% in Hs 578 cells. Thus, use of anti-laminin receptor monoclonal antibodies coupled with liposomes encapsulating doxorubicin represents a new strategy for selective targeting of doxorubicin to carcinoma cells with exposed laminin receptors.

Antibodies, Monoclonal

Absorption and tissue distribution of various polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDDs and PCDFs) in the rat.

A defined mixture of polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDDs and PCDFs) was parenterally administered to rats and absorption and tissue distribution were measured: 1) Toluene/DMSO (1 + 2; v/v) proved to be a convenient vehicle for the subcutaneous administration of the various PCDDs and PCDFs. Seven days after application the rate of absorption was 90% of the administered dose or even higher for almost all of the PCDDs/PCDFs in the mixture. In a few cases only (e.g. OCDD) the rate was found to be 84-89%; 2) Seven days after subcutaneous administration all 2378-substituted congeners were found in the liver, whereas only a few non-2378-substituted congeners could be measured in minor quantities. The 2378-substituted congeners also predominated in adipose tissue; however, most of the non-2378-substituted congeners were also detected; 3) The amount deposited within the liver as percentage of the administered dose differed for the various 2378-substituted PCDDs and PCDFs, ranging from less than 10% for OCDD or 2378-T4CDF, and between 60 and close to 100% for 12378-P5CDD or the H6CDDs. Therefore, the concentration ratio (liver/adipose tissue) was also found to be very different, ranging from less than 3 in the case of 2378-T4CDD or 2378-T4CDF to greater than 40 in the case of 1234678-H7CDD, 23478-P5CDF, 123678-H6CDF, or 1234678-H7CDF; 4) Studies performed at the time period of ongoing absorption (13-14 h after injection) provided the first evidence that some of the non-2378-substituted congeners do reach substantial concentrations in hepatic tissue shortly after administration; 5) Subsequent to intraperitoneal injection of the same PCDD/PCDF mixture the concentrations within the liver were found to be almost identical with that found after subcutaneous injection. In contrast, much higher concentrations of the congeners were found in (abdominal) adipose tissue; 6) In the liver of untreated rats of the same strain no T4CDDs/T4CDFs or P5CDDs/P5CDFs were detectable under our experimental conditions.

Animals

Elimination of various polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDDs and PCDFs) in rat faeces.

A defined mixture (of a composition characteristic of that present in incinerator fly ash) of polychlorinated dibenzo-p-dioxins and -furans (PCDDs and PCDFs) was subcutaneously administered to rats and the elimination of the unchanged congeners via faeces was measured. 1) All congeners administered could be found in faeces. 2) The rates of elimination via faeces were rather different for the different congeners. 3) The most toxic congeners, 2378-T4CDD and 12378-P5CDD, were present in unmetabolized form in faeces to less than 4% and less than 8% of the administered dose within the first week. Thus, parenteral administration clearly minimizes contamination of the animal quarters when compared with corresponding oral dosing. 4) The rate of unchanged elimination was apparently especially pronounced for the higher chlorinated PCDDs and PCDFs. The highest excretion rate was found for 1234678-H7CDD (up to 30% of administered dose). 5) No obvious differences were observed in the rates of elimination of the unchanged substances via faeces of the 2378-substituted or the non-2378-substituted isomers.

Animals

Synchronous adenocarcinoma and carcinoid of the uterine cervix: immunohistochemical study of a case and review of literature.

Mixed neoplasms, adenocarcinoma and carcinoid, have been reported to occur in several areas of the body, including gastrointestinal tract, breast, prostate, lung, skin, and kidney. Mixed tumors of the uterine cervix are very rare. Their histogenesis, immunohistochemical profile, and prognosis are not well established. Here, we report a case of a 49-year-old female with infiltrating adenocarcinoma of the cervix within which was found a separate nodule of small cell endocrine carcinoma.

Adenocarcinoma

Pharmacokinetics and biological activity of 2,3,7,8-tetrachlorodibenzo-p-dioxin. 1. Dose-dependent tissue distribution and induction of hepatic ethoxyresorufin O-deethylase in rats following a single injection.

Concentrations of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) in rat liver and adipose tissue, and hepatic ethoxyresorufin O-deethylase (EROD) activity were studied subsequent to a single subcutaneous injection of TCDD. Two types of experiments were performed to study: (a) time-dependent changes following a single injection of 300 ng TCDD/kg body wt (points 1-4), and (b) dose-dependent changes measurable after 7 days following a single injection (points 5-7). 1. Absorption of TCDD following a single subcutaneous injection was about 90% after 3 days and 98% after 5 days. 2. Following a single dose of 300 ng TCDD/kg body wt peak concentrations were: liver (after 3 days): 4.7 +/- 0.9 ng/g wet wt, and adipose tissue (after 7 days): 0.82 +/- 0.07 ng/g wet wt. 3. T1/2 of TCDD in liver was 13.6 days over the total experimental period (from day 10 to 91 of the study), apparently with an initial faster phase: 11.5 days (from day 10 to 49), and a slower period at the end of the experiment: 16.9 days (from day 49 to 91); in adipose tissue the t1/2 was 24.5 days (from day 14 to 91 of the study). 4. Maximum induction of EROD in the liver was observed (14-fold at 300 ng TCDD/kg body wt) 3-7 days following the injection; the activity was decreased to about one third of the maximum 3 weeks after the injection; increase in total cytochrome P-450 at this dose was only about 1.4-fold at the induction maximum. 5. The ratio of the TCDD concentrations in liver and adipose tissue increased considerably between doses of 3 ng TCDD/kg body wt (ratio: about 0.74) and 3000 ng TCDD/kg body wt (ratio: about 7.7). 6. The extent of EROD induction in the liver increased dose dependently. A significant effect was first observed with a dose of 3 ng TCDD/kg body wt (activity about +32% above control activity). The corresponding tissue concentration was about 10 pg TCDD/g liver wet wt. 7. An almost perfect linear relationship exists (when using a double-log plot) between the hepatic TCDD concentration and the EROD activity for tissue concentrations ranging from 40 to 30,000 pg TCDD/g wet wt.

Adipose Tissue

[Brain tumor diagnosis using 3-detector-gamma-encephalography].

The probability of diagnosis of brain tumours by means of 3-detector-gamma-encephalography (Hg 197-Neohydrin) is higher than that of the scintigraphic procedures so far available. Above all, the diagnostic accuracy of foci with low storage rates and space-occupying processes of the infratentorial region is improved. The short duration of the examination allows the method to be applied as a screening test.

Brain Neoplasms