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Biomedical subjects

A Rasmussen

Publications and source records attributed to A Rasmussen.

At least 37 records · Page 2Linked to original sources
PubMed1999

Reconstitution of the actin-scavenger system after orthotopic liver transplantation for end-stage liver disease: a prospective and longitudinal study.

Serum levels of the actin scavenger Gc-globulin (group-specific component, vitamin D-binding protein), a member of the albumin multigene family, are decreased in severe liver disease but have not been evaluated in relation to liver transplantation. We measured Gc-globulin and Gc-globulin-actin complex ratio daily for 2 weeks after transplantation in 17 patients with end-stage liver disease. Before transplantation, Gc-globulin levels were significantly less in the patients than in healthy controls (235 +/- 106 v 340 +/- 35 mg/L, respectively; P<.001), whereas complex ratio level was in the normal range. Five patients (group N) had pretransplantation Gc-globulin values within the normal range (mean +/- 2 SD), and 12 patients had subnormal values (group S). In group N, mean Gc-globulin levels posttransplantation remained stable at a lower level than before transplantation but still within normal range. In this group, cold ischemia time correlated inversely with Gc-globulin levels on day 2 (r = -0.88; P <.05). In group S, normal mean levels were reached at a mean of 11 days after transplantation. However, almost half these patients had subnormal Gc-globulin levels at day 14. Complex ratio levels remained normal in the study period in both groups. Prothrombin index levels (plasma coagulation factors II, VII, and X) were identical in both groups and returned to normal 7 days posttransplantation, whereas plasma albumin levels were less than normal in both groups and further decreased after transplantation. In conclusion, the maintenance (group N) or reestablishment (group S) of serum Gc-globulin to normal levels occurred in the early posttransplantation course in the same time frame as the prothrombin index. Gc-globulin synthesis seems unrelated to albumin synthesis. A prolonged cold ischemia time may cause reduced Gc-globulin levels early after transplantation.

Actins↗
PubMed1999

Endoscopic ultrasound duplex scanning for measurement of portal venous flow. Validation against transit time ultrasound flowmetry in pigs.

BACKGROUND: Endoscopic ultrasound (EUS) is a new technique that makes it possible to measure portal venous flow when transabdominal ultrasound fails. As the technique has not been evaluated previously, we compared simultaneous measurements of portal venous flow using EUS Doppler with that of transit time ultrasound (TTU) in healthy pigs. The ability of EUS to detect changes in the portal venous flow after pharmacologic intervention was also investigated. METHODS: Six anaesthetized pigs were studied. Portal venous flow was measured simultaneously by EUS duplex scanning, using a Pentax FG-32UA echoendoscope connected to a Hitachi EUB 515-A ultrasound scanner, and by TTU with a Cardiomed CM 4000 flowmeter probe placed on the portal vein. Terlipressin, 1 mg, and placebo were administered in a blind, randomized, crossover design. Measurements were taken at base line and 30 min after each drug administration. RESULTS: Portal venous flow measured by EUS flowmetry and TTU flowmetry correlated significantly (R = 0.92, P < 0.001, n = 18). The limits of agreement in a Bland-Altman plot were from -0.262 l/min to +0.164 l/min. The change in portal venous flow after terlipressin measured by EUS and TTU correlated significantly (R = 0.88, P < 0.05, n = 6). All values used for analyses were the means of five repeated measurements. CONCLUSIONS: EUS measures portal venous flow with an acceptable correlation and agreement with TTU in anaesthetized pigs. The method is capable of monitoring the effects of pharmacologic intervention on the portal system.

Animals↗
PubMed1998

[Atraucan, a new needle for spinal analgesia].

One hundred and six consecutive patients, aged below 40 years, scheduled for surgery in the lower part of the body were chosen for this study. Patients were allocated randomly to have spinal analgesia with either a Sprotte 24G or an Atraucan 26G spinal needle. Incidences of insufficient blocks were higher after dural puncture with the Atraucan needle. Nineteen patients reported post dural puncture headache (PDPH) with a significantly higher proportion in the Atraucan group (two patients suffered mild (4%) and 14 severe (98%) PDPH) compared to the Sprotte group (three patients suffered mild (6%) PDPH. Eight patients (16%), all in the Atraucan group, required an epidural blood patch. Ease of needle insertion and number of puncture attempts were the same for both needles. We conclude that due to the high incidence of PDPH the Atraucan 26G spinal needle cannot be recommended for spinal analgesia in young patients.

Adult↗
PubMed1998

Liver transplantation with cavoportal hemitransposition in the presence of diffuse portal vein thrombosis.

BACKGROUND: Orthotopic liver transplantation is possible even in the presence of recipient portal vein thrombosis, provided that hepatopetal portal flow to the graft can be restored. On rare occasions this is not possible due to diffuse thrombosis of the portal venous system. In these cases, successful liver transplantation has been considered impossible. Portocaval transposition was introduced in the pretransplantation era to study the effect of systemic venous flow on the liver and has been used in three patients for the treatment of glycogen storage disease. We used portocaval hemitransposition (portal perfusion with inflow from the inferior vena cava) in liver transplantation when portal inflow to the graft was not feasible. We are reporting the collective experience of nine patients from four liver transplant centers. METHODS: Cavoportal hemitransposition was used in nine patients. In seven of these cases, the technique was used during the original transplant (primary group). In two cases, it was used after the portal inflow to the first transplant had clotted (secondary group). RESULTS: Five of seven patients in the primary group are alive after intervals of 6-11 months. The two patients in the rescue group died. In the successful cases, liver function and histology were indistinguishable from those of conventional liver transplantation. Ascites disappeared within 3-4 months and the patients were able to return to their normal activities. Postoperative variceal bleeding necessitated splenectomy and gastric devascularization in one case and splenic artery embolization in another case. Bleeding was controlled in both these cases. Splenectomy and gastric devascularization were performed prophylactically in one patient with a history of variceal bleeding in order to prevent this complication after transplantation. CONCLUSION: Portocaval hemitransposition maybe useful in liver transplantation when hepatopetal flow to the liver graft cannot be established by other techniques. Rescue after failure of conventional technique was not possible in two patients.

Adult↗
PubMed1998

Stromal IGF-II messenger RNA in breast cancer: relationship with progesterone receptor expressed by malignant epithelial cells.

In breast cancer, insulin-like growth factor II (IGF-II) is stromal in origin and is considered an important regulator of tumour epithelium growth. The presence of progesterone receptor (PR) is expression of an intact oestrogen regulatory pathway of breast malignant epithelial cells and represents a parameter of cell differentiation in breast cancer. In this study we have examined the relationship between IGF-II mRNA expression and ER, PR content in 75 breast cancer. Formalin-fixed paraffin-embedded tissue sections were used to preserve histological details. IGF-II mRNA was evaluated by in situ hybridisation method and ER, PR by immunohistochemistry. IGF-II mRNA was scored semi-quantitatively: 2.6% breast tumour specimen expressed no IGF-II mRNA, 46.7% had low levels of expression (IGF-II-) and 50.7% had moderate or high IGF-II mRNA content (IGF-II+). IGF-II mRNA was found in the stroma fibroblasts surrounding malignant lesions and no signal was detected in malignant epithelial cells. In contrast, ER and PR were expressed only by neoplastic epithelial cells and no immunoreactivity was found in the stroma: 50/75 (66.6%) breast cancer specimens were positive for ER (ER+) and 35 (46.6%) for PR (PR+). Both, IGF-II mRNA and PR were directly correlated with the stromal proliferation (p < 0.05 and p < 0.001, respectively). No relationship was found between IGF-II RNA and ER. In contrast 24/35 (73.5%) PR breast cancer tissues were IGF-II+ (p < 0.01) and a strong correlation was found between epithelial PR immunostaining and stromal IGF-II mRNA content (p < 0.003). Our data indicate that in breast cancer IGF-II mRNA is generally expressed by stromal cells and ER and PR by epithelial cancer cells, and that IGF-II mRNA expression is strongly related with both percentage and staining intensity of PR+ epithelial cancer cells. These data support the hypothesis that IGF-II produced by the fibroblasts may exert a paracrin effect on malignant epithelium regulating its differentiation.

Breast Neoplasms↗
PubMed1997

Primary human hepatocytes as a tool for the evaluation of structure-activity relationship in cytochrome P450 induction potential of xenobiotics: evaluation of rifampin, rifapentine and rifabutin.

In our laboratory, primary human hepatocytes are being investigated as an in vitro experimental system for the evaluation of pharmacokinetic drug-drug interactions. Our study here represents the first reported study that directly compares the cytochrome P450 isozyme 3A (CYP3A) induction potential of three antimicrobials derived from rifamycin B, namely, rifampin, rifapentine and rifabutin. Two endpoints of CYP3A activity, testosterone 6 beta-hydroxylation and midazolam 1-hydroxylation have been used. Results obtained with hepatocytes from four different human donors show consistently that rifampin and rifapentine are potent inducers of CYP3A, while a significantly lower induction potential is observed for rifabutin. The relative induction potency of the three antimicrobials (rifampin > rifapentine >> rifabutin) is consistent with the available human in vivo data. For CYP1A measured as ethoxyresorufin O-deethylase activity, CYP2C8/9 measured as tolbutamide 4-hydroxylation activity, CYP2D6 measured as dextromethorphan O-demethylation, and AZT glucuronidation, there is either no effect or, where induction is found to be statistically significant in these other endpoints, the maximum induction values are consistently < 100% of the control. Our results suggest that CYP3A is the major CYP induced by these rifamycin B derivatives. These studies illustrate the application of human hepatocytes in the evaluation of the structure-activity relationships in CYP induction for this class of chemicals and as an in vitro screen for drug-drug interaction potential via CYP induction.

Antibiotics, Antitubercular↗
PubMed1997

Liver function, cerebral blood flow autoregulation, and hepatic encephalopathy in fulminant hepatic failure.

In acute liver failure, massive hepatic necrosis may result in impaired regulation of cerebral blood flow (CBF), development of encephalopathy, and cerebral edema. In 10 consecutive patients with fulminant hepatic failure (FHF), CBF autoregulation was found to be absent, as transcranial Doppler mean flow velocity (Vmean) in the middle cerebral artery increased from 49 (27-59) to 69 (49-92) cm/s (P < .05) during a 30- (28-34) mm Hg rise in mean arterial pressure (MAP). In 7 patients, restoration of CBF autoregulation was shown within 48 (24-120) hours after spontaneous hepatic recovery or liver transplantation, before complete alleviation of hepatic encephalopathy (HE). The extraordinarily rapid restoration of CBF autoregulation in patients with FHF following re-establishment of liver function is unique compared with other conditions affecting the CBF autoregulation, indicating a close connection between liver function and regulation of cerebral circulation. Because CBF autoregulation was restored after initial alleviation of HE, it does not appear to be of major pathophysiological importance in the mediation of HE.

Adult↗
PubMed1997

Lower body impedance for the evaluation of venovenous bypass flow.

Inferior vena cava (IVC) clamping during liver transplantation causes venous congestion in the splanchnic and IVC beds. A venovenous bypass relieves congestion and improves cardiac output (CO), but the bypass flow required for adequate drainage of the vascular beds is controversial. In this study we evaluated the bypass flow necessary to compensate for the IVC clamping. Lower body impedance (BI) is inversely related to tissue fluid content and was used to reflect congestion. A venovenous bypass was successfully applied to 59 of 62 patients. BI was measured across the left buttock and related to bypass flow, CO, bypass flow ratio (bypass flow/CO before IVC clamping; n = 62), and right femoral venous pressure (n = 8). The bypass flow was 1.7 (0.0-3.0) L.min-1 (median and range). BI decreased (delta BI; -2.2 [-10.3-1.1)] omega) as the femoral venous pressure increased (29 [21-49] mm Hg; r = -0.81; P < .05), and the femoral venous pressure correlated inversely to bypass flow (r = -0.35; P < .01). The change in CO at IVC clamping (delta CO; -2.3 [-6.3-1.6] L.min-1) related to bypass flow ratio (0.25 [0-0.51]; r = 0.57, P < .01), whereas delta BI related only minimally to bypass flow or bypass flow ratio (r = 0.37; P < .05). In conclusion the median bypass flow of 1.7 L.min-1 was too small to prevent fluid accumulation in the lower caval region, and extrapolation of data suggests that bypass flow should have approached 3.5 L.min-1 or 50% of CO in order to prevent fluid accumulation in the lower caval region. However the minimal correlation between lower BI and bypass flow indicates that bypass flow per se is not the only determinant of lower body fluid accumulation.

Adult↗
PubMed1997

Neoral in de novo liver transplantation: adequate immunosuppression without intravenous cyclosporine.

Absorption of cyclosporine from the traditional oral formulation Sandimmune (Novartis Pharma, Basel, Switzerland) is particularly unpredictable in the early stages after liver transplantation. The absorption of cyclosporine is influenced by liver function, postoperative paralytic ileus, and graft dysfunction. Oral absorption of cyclosporine from Sandimmune is also bile dependent; cholestasis and external biliary drainage are associated with low cyclosporine absorption. Postoperative administration of intravenous Sandimmune is therefore often necessary to obtain adequate immunosuppression, despite the increased risk of renal and neurological toxicity. A microemulsion formulation of cyclosporine, Neoral (Novartis), has been developed to overcome the problems of poor and variable absorption of cyclosporine from Sandimmune. Uptake of cyclosporine from Neoral is rapid and less dependent on bile secretion so that higher peak concentrations are reached and absorption is less variable than with Sandimmune. A review of several open studies in which Neoral was administered to liver transplant patients immediately after transplantation is presented. The results suggest that the use of Neoral as a primary immunosuppressive therapy provides adequate cyclosporine trough levels, minimizing or obviating the need for intravenous cyclosporine administration. In addition, Neoral appears to reduce the risk of acute rejection episodes compared with immunosuppressive regimens involving intravenous cyclosporine.

Absorption↗
PubMed1997

Intraoperative measurement of graft blood flow--a necessity in liver transplantation.

Portal venous and hepatic arterial flow was measured intraoperatively in the 70 most recent patients undergoing liver transplantation in our institution. Impaired graft flow due to vascular abnormalities was detected in six patients. One patient suffered from arterial steal due to stenosis of the recipient celiac trunk with blood shunting from the hepatic to the splenic artery. Ligation of the recipient hepatic artery restored the arterial graft flow. In two patients we found reduced portal venous flow due to large portosystemic collaterals. The collaterals accountable for the impaired portal flow were identified and ligated, which restored portal venous graft flow. Excessive sensitivity of the portal venous flow to the position of the graft was found in a 6-month-old boy. Portal venous flow varied considerably, depending upon the position of the graft, and intraoperative flow measurement allowed the best position of the graft to be identified. Two patients developed arterial thrombosis in the early postoperative course. Immediate laparatomy with thrombectomy resulted in good, palpable pulsation in the graft artery in both patients. Intraoperative flow measurement demonstrated satisfactory arterial flow in one patient, whereas there was no net flow in the other patient's graft artery. Pulsation in this patient was caused by blood oscillating in and out of the liver. In conclusion, we find that causes of primary graft dysfunction due to technically flawed reperfusion of the graft can be identified and alleviated by intraoperative measurement of the flow in the graft vessels.

Adult↗
PubMed1997

Cerebral oxygen saturation and blood flow during liver transplantation.

After reperfusion of a liver graft, transcranial Doppler determined middle cerebral artery flow velocity, increases more than expected from the arterial carbon dioxide tension (PaCO2). We evaluated if this indication of cerebral hyperperfusion is reflected in the jugular oxygen saturation (SjO2) (n = 31) and oxygen saturation (ScO2) (near-infrared spectrophotometry, n = 22). From the dissection phase to the anhepatic phase SjO2 71.0% (range 62.3%-78.5%), ScO2 70% (range 65%-77%), and PaCO2 34.9 mm Hg (range 30.8-38.3) remained statistically unchanged. In contrast, during the early reperfusion phase, SjO2 increased to 77.0% (71.4%-83.0%) (P < 0.01) and the ScO2 to 75% (68%-80%) (P < 0.05) as PaCO2 increased to 37.5 mm Hg (34.8-41.9) (P < 0.001). Notably, SjO2 also increased at reperfusion from 71.6% (66.5%-78.0% mm Hg) to 80.0% (76.8%-84.8%) in the four patients in whom PaCO2 decreased at reperfusion from 37.6 mm Hg (36.8-39.5) to 34.0 mm Hg (32.3-36.8). If the changes in SjO2 after reperfusion of the grafted liver should be explained as a reflection of changes in cerebral blood flow, in response to PaCO2, it would indicate a highly accentuated CO2 reactivity of 13%/mm Hg. The results support that cerebral blood flow and, in turn, oxygenation increase after reperfusion because the grafted liver liberates a vasodilating substance(s).

Adolescent↗
PubMed1997

Coexpression of stromelysin-3 and insulin-like growth factor II in tumors of ectodermal, mesodermal, and endodermal origin: indicator of a fetal cell phenotype.

Stromelysin-3 (ST-3) is thought to play an important role in invasion and tumor progression. We have analyzed ST-3 expression in fibroblasts with defined topographical relations to breast cancers. We demonstrate that these fibroblasts exhibit the same distinctive pattern of messenger ribonucleic acid (mRNA) expression that we have previously shown for insulin-like growth factor II (IGF-II). Tumor-derived fibroblasts and skin fibroblasts produce abundant ST-3 mRNA. Fibroblasts from normal breast stroma distant from the malignant tumor in the same patient express considerably less ST-3 mRNA. When we analyzed ST-3 and IGF-II gene expression in sarcomas, we found a similar pattern of coexpression. Immunohistochemical analysis of IGF-II and ST-3 protein expression in sarcomas and breast tumors confirmed the mRNA data. ST-3 mRNA expression was also seen in most colon cancer cell lines, again matching reports of IGF-II gene expression. As the two proteins are known to play an important role during fetal growth and development, their coexpression in fibroblasts from malignant tumors of ectodermal (breast cancer) and mesodermal (sarcoma) origin and in epithelial cells of endodermal origin (colon cancer) implies a more primitive cellular phenotype. The regained ability to express such developmentally regulated proteins might, therefore, be a more general marker indicating a fetal-type phenotype of cells in a malignant tumor.

Breast Neoplasms↗
PubMed1997

Effect of long-term implanted nerve cuff electrodes on the electrophysiological properties of human sensory nerves.

During a long-term implantation (307 days) of a tripolar split cuff electrode around the palmar digital nerve to the radial side of the left index finger, branching off the median nerve in a medullary lesioned C6 patient, the physiological state of the nerve was intensively monitored. The resulting sensory nerve action potential (SNAP) amplitude was recorded, using both near-nerve electrodes and the implanted cuff electrode. The SNAP amplitude declined within 10 days to approximately 50% of the first SNAP cuff amplitude measured on Day 2 after implantation and recovered to the initial amplitude within 3 months. The SNAP amplitude measurements made with near-nerve electrodes were consistent with the cuff results; the SNAP conduction velocity (CV) recorded by the near-nerve electrodes and the cuff electrode was constant during the whole implantation period. This is in agreement with the results from two other patients: one with a cuff implanted around the sural nerve, and the other with a cuff implanted around a branch of the tibial nerve. These results and animals studies show that the cuff electrode is an electrically stable neural-electrical transducer.

Action Potentials↗
PubMed1996

Induction of immunosuppression by microemulsion cyclosporine in liver transplantation.

Twenty-five liver transplant patients were administered liquid microemulsion cyclosporine (Neoral, 5 mg/kg b.i.d.) via a nasogastric tube until they could take oral medication. The first dose was given within 6 hr after surgery. Adequate trough levels of cyclosporine were obtained from the first postoperative day. The total exposure to the drug was low on the first postoperative day, but a significantly improved pharmacokinetic profile with a high maximal concentration and a low time to maximal concentration was found from the second postoperative day. The absorption from Neoral increased during the first week. After 1 week, a low within-patient variation coefficient for dose-adjusted cyclosporine trough levels was found (17%). The between-patient variation coefficient was low during the whole postoperative period (31%). We conclude that in liver transplant patients adequate immunosuppressant blood levels of cyclosporine can be obtained in the immediate postoperative period using Neoral without the need to go to the intravenous form of the drug.

Antilymphocyte Serum↗
PubMed1996

Donor arterial variations in liver transplantation: management and outcome of 527 consecutive grafts.

The impact of donor arterial variations and their management was investigated retrospectively in 527 consecutive allografts. Anomalous arteries were found in 161 grafts (30.6 per cent). There was no significant difference in the overall incidence of arterial complications between grafts with normal (3.6 per cent) and abnormal (5.6 per cent) anatomy. However, there was a higher incidence of arterial complications in transplants requiring multiple arterial anastomoses (P = 0.02), or anastomosis of donor vessels to recipient aorta with (P = 0.0003) or without (P = 0.04) an interposition graft for arterial reconstruction. The incidence of biliary complications was similar in grafts with a normal (18.8 per cent) or anomalous (18.0 per cent) arterial supply. Anomalies of hepatic arterial anatomy occur in one-third of all livers and do not compromise graft outcome unless multiple anastomoses or direct anastomosis to the recipient aorta are required for arterial reconstruction.

Aneurysm↗
PubMed1996

IGF-II mRNA and protein are expressed in the stroma of invasive breast cancers: an in situ hybridization and immunohistochemistry study.

Insulin-like growth factor-II (IGF-II) is a potent mitogen for a variety of cell types and is considered an important regulator of breast cancer growth. In this study, we analyzed IGF-II mRNA and protein expression in a series of 80 cases of invasive breast cancer. Seventy-five cases produced informative results for IGF-II mRNA expression, and were scored on an arbitrary scale. Two cases (2.6%) had no significant IGF-II mRNA expression. 35 cases (46.7%) expressed low levels of IGF-II mRNA, 20 cases (26.7%) moderate IGF-II mRNA, while 18 (24%) expressed high levels of IGF-II message. Generally, IGF-II mRNA was expressed in the smooth muscle walls of blood vessels and ducts, as well as in the stroma tightly adjacent to and surrounding tumor epithelium. IGF-II mRNA content was also directly related to the amount of the stroma within the tumor (p < 0.05). In 10 cases (13.3%) IGF-II mRNA was detected in the stroma of normal lobules. Fifty-six out of 75 were positive for IGF-II immunostaining. Again, protein staining was generally observed in the smooth muscle of both blood vessels and ducts, as well as in the stroma surrounding tumor epithelium. In normal lobules and ducts the IGF-II protein was detected in the myoepithelium. Unequivocal IGF-II protein staining was seen in tumor epithelium in only three cases. The results of our study demonstrate that, in breast cancer, IGF-II mRNA is expressed in the smooth muscle and stromal components in the majority of invasive breast cancers. IGF-II expression correlates positively with the amount of stromal tissue present within a tumor. This suggests that IGF-II may have an important growth regulatory effect on breast tumor epithelium through paracrine pathways.

Adult↗