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Biomedical subjects

A Rasmussen

Publications and source records attributed to A Rasmussen.

At least 19 recordsLinked to original sources
PubMed2006

Treatment of anthracycline extravasation with Savene (dexrazoxane): results from two prospective clinical multicentre studies.

BACKGROUND: The purpose of this study was to assess the efficacy and tolerability of i.v. dexrazoxane [Savene (EU), Totect (US)] as acute antidote in biopsy-verified anthracycline extravasation. PATIENTS AND METHODS: Two prospective, open-label, single-arm, multicentre studies in patients with anthracycline extravasation were carried out. Patients with fluorescence-positive tissue biopsies were treated with a 3-day schedule of i.v. dexrazoxane (1000, 1000, and 500 mg/m(2)) starting no later than 6 h after the incident. Patients were assessed for efficacy (the possible need for surgical resection) and toxicity during the treatment period and regularly for the next 3 months. RESULTS: In 53 of 54 (98.2%) patients assessable for efficacy, the treatment prevented surgery-requiring necrosis. One patient (1.8%) required surgical debridement. Thirty-eight patients (71%) were able to continue their scheduled chemotherapy without postponement. Twenty-two patients (41%) experienced hospitalisation due to the extravasation. Mild pain (10 patients; 19%) and mild sensory disturbances (nine patients; 17%) were the most frequent sequelae. Haematologic toxicity was common as expected from the fact that the extravasation occurred during a chemotherapy course. Other toxic effects were transient elevation of alanine aminotransferases, nausea, and local pain at the dexrazoxane injection site. CONCLUSION: Dexrazoxane proved to be an effective and well-tolerated acute treatment with only one out of 54 assessable patients requiring surgical resection (1.8%).

Adult↗
PubMed2006

Clinical heterogeneity of recessive ataxia in the Mexican population.

Approximately 75% of Indo-European patients with recessive ataxia are homozygous for frataxin gene (FXN) mutations and have either typical or atypical Friedreich ataxia (FRDA). Our previous analysis of 134 Mexican Mestizo recessive ataxia patients showed that FRDA is relatively uncommon in the Mexican population (10.4%). This article reports the evaluation of the phenotypes of these patients. Over half of the patients with clinical diagnostic criteria for FRDA did not carry FXN mutations, constituting a "FRDA-like" phenotypic subgroup. Analysis of non-FRDA patients revealed a subgroup with early onset recessive cerebellar ataxia and cognitive deficit. These two phenotypic subgroups accounted for approximately 60% of all patients, indicating that the cause for recessive ataxia in the Mexican population is distinct from other populations and remains largely unknown.

Adolescent↗
PubMed2003

Huntington's disease--like 2 can present as chorea-acanthocytosis.

Three patients from a previously described family with autosomal dominant chorea-acanthocytosis were found to have the CTG trinucleotide repeat expansion mutation of the junctophilin-3 gene associated with Huntington's disease-like 2 (HDL2). One of six previously identified patients with HDL2 had acanthocytosis on peripheral blood smear, suggesting that HDL2 should be considered in the differential of chorea-acanthocytosis.

Acanthocytes↗
PubMed2003

Platelet serotonin transporter in stroke patients.

OBJECTIVES: Post-stroke depression can be treated with serotonin transport inhibitors suggesting a role for the serotonin system in these patients. The number of platelet serotonin transporters in stroke patients and in control subjects have been measured in this study. MATERIAL AND METHODS: Newly admitted stroke patients who did develop or who did not develop a post-stroke depression, non-acute patients who previously had had a stroke and control subjects were compared. The number of platelet serotonin transporters was analysed by ligand binding methodology. RESULTS: The number of platelet serotonin transporters was low shortly after a stroke compared with normal subjects; no difference was found between the stroke patients who developed a post-stroke depression and those who did not. CONCLUSION: A low number of platelet serotonin transporters may be a non-specific state marker for a condition as acute stroke.

Acute Disease↗
PubMed2002

Homozygosity in Huntington's disease: new ethical dilemma caused by molecular diagnosis.

Huntington's disease (HD) is a degenerative disorder of the central nervous system with autosomal dominant inheritance. Genetic counseling has always been difficult in this disorder with anguish, depression and denial being very common in both the patient and family members. The discovery of the causal gene has led to precise diagnostic procedures allowing homozygotes for the disease to be identified. Contrary to what occurs in some other autosomal dominant diseases, the course of the disease is not more severe in the homozygote than in the heterozygote. The present authors describe a family comparing two affected siblings: one is heterozygotic and the other homozygous for the HD mutation. They confirm that the age and symptoms of onset did not differ significantly between the subjects; however, the disease seemed to have a more severe progression in the heterozygote than in the homozygote. The authors discuss the ethical dilemma derived from the genetic counseling of a homozygotic patient, given the fact that all his offspring will be affected. Letting the offspring know about their 100% probability of inheriting the disorder is equivalent to delivering a non-requested predictive test, while not informing them constitutes withholding crucial information from the individual.

Age of Onset↗
PubMed2002

Allergen sensitization and allergen exposure in Greenlander Inuit residing in Denmark and Greenland.

The aim of this study was to estimate the prevalence of allergic sensitization and possible risk factors in a genetically homogenous Inuit population living under widely differing climatic and cultural conditions. A written questionnaire and skin prick test for 10 aeroallergens were obtained from 1119 adult Greenlanders residing in Denmark, Nuuk (main city in Southern Greenland) and Uummannaq (rural settlement in Northern Greenland). Allergen exposure was assessed by pollen counts, questions on pet keeping and counts of house dust mites in dust samples. The overall prevalence of at least one positive skin prick test was 22.8% in Denmark, 10.6% in Nuuk, and 6.4% in Uummannaq. In Denmark, the total birch pollen counts were 40-1000 times higher compared to Nuuk, whereas the grass pollen count was 13-30 times higher in Denmark compared to Nuuk. Dogs were held indoor with a similar frequency in Denmark and Nuuk, but much less frequently in Uummannaq. In Denmark, house dust mites were found in 72% of house holds (>10/0.1 g dust). Less than 15% of households in Greenland had measurable levels of house dust mites. The prevalence of sensitization to aeroallergens in Inuit Greenlanders differed significantly between Denmark, Nuuk and Uummannaq. These findings correlated with the observed differences in population allergen exposure in the three regions. Furthermore, differences in lifestyle factors such as educational level, stress and ethnic self-identification seemed to be associated with the risk of allergic sensitization in Greenland.

Adolescent↗
PubMed2001

Clinical and genetic analysis of four Mexican families with spinocerebellar ataxia type 10.

Spinocerebellar ataxia type 10 (SCA10) is an autosomal dominant disorder caused by expansion of an unstable ATTCT repeat. SCA10 has been described as a pure cerebellar syndrome accompanied by seizures and has been recognized only in families of Mexican origin. We describe clinical and molecular findings of 18 patients in four Mexican families with SCA10. Affected individuals had an average age at onset of 26.7 years (range 14-44 years) and ATTCT repeats ranging from 920 to 4,140 repeats. We could not detect significant anticipation or correlation between repeat size and age at onset, probably due to the small sample size. In addition to pure cerebellar ataxia and seizures, patients often showed soft pyramidal signs, ocular dyskinesia, cognitive impairment, and/or behavioral disturbances. Brain magnetic resonance imaging showed predominant cerebellar atrophy, and nerve conduction studies indicated polyneuropathy in 66% of patients. One family showed hepatic, cardiac, and hematological abnormalities in affected members. These findings suggest that a wide range of tissues may be affected in SCA10, including those outside of the cerebellum and cerebral cortex.

Adolescent↗
PubMed2001

The effect of selective bowel decontamination on the pharmacokinetics of mycophenolate mofetil in liver transplant recipients.

Mycophenolate mofetil (MMF) is a prodrug immunosuppressant with a high oral bioavailability. Enterohepatic cycling of a glucuronide derivative of MMF contributes substantially to the bioavailability, but is dependent on bacterial deglucuronidation by intestinal flora. This study aims to determine whether an antibiotic regimen with activity against such organisms reduces the bioavailability of MMF by impairing enterohepatic cycling. In a prospective trial, 6 liver transplant recipients were administered MMF and a 21-day antibiotic regimen for selective bowel decontamination (SBD). Time-concentration profiles of the pharmacologically active metabolite, mycophenolic acid (MPA), were obtained during and after the SBD regimen. The bioavailability of MPA was reduced during compared with after the regimen (14.5 +/- 3.5 v 21.1 +/- 9.8 mg. h/mL; P =.07). The most pronounced contribution to this reduction was observed from 6 hours onward (2.4 +/- 1.4 v 5.6 +/- 4.4 mg. h/mL; P <.05). The presence of secondary maxima in the time-concentration profiles of MPA after, but not during, SBD indicates that enterohepatic cycling may be inhibited during SBD and restored afterward. Enterohepatic cycling may contribute 7% to 54% (mean, 29%) of the bioavailability of MPA. We conclude that the bioavailability of MMF may be reduced when SBD is used, and the reduction is likely to result from the interruption of enterohepatic cycling. This mechanism should be taken into consideration not only during SBD, but in any clinical setting combining MMF and broad-spectrum antibiotics.

Adult↗
PubMed2001

Distribution and mRNA expression of insulin-like growth factor system in pulmonary lymphangioleiomyomatosis.

BACKGROUND: Insulin-like growth factors (IGF-1 and IGF-2), the IGF-1 receptor (IGF-1R), and IGF-binding proteins (IGFBPs) are involved in normal pulmonary development and in the pathogenesis of smooth muscle cell tumors. METHODS: To evaluate the role of the IGF system in lymphangioleiomyomatosis (LAM), we used immunohistochemical and in situ hybridization techniques to characterize the expression of IGF-1, IGF-2, IGF-1R, and IGFBP-2, -4, -5, and -6 in lung tissue from 18 LAM patients. RESULTS: IGF-1, ICGF-2, IGF-1R, IGFBP-1, IGFBP-2, IGFBP-4, IGFBP-5, and IGFBP-6 were expressed by LAM cells. Reactivity and mRNA expression for IGF-2 were observed in LAM cells and resembled that found in normal smooth muscle cells during pulmonary development as well as in smooth muscle cell tumors. IGFBP-2, IGFBP-4, and IGFBP-6 were associated with spindle-shaped LAM cells, whereas IGFBP-5 was associated mainly with epithelioid LAM cells. CONCLUSIONS: These findings suggest that the IGFBPs modulate the effects of the IGFs on LAM cells. Thus, the patterns of localization and expression of components of the IGF system in LAM strongly suggest that these agents are involved in the proliferation of LAM cells.

Adult↗
PubMed2001

Early postoperative erythromycin breath test correlates with hepatic cytochrome P4503A activity in liver transplant recipients.

BACKGROUND: Interindividual variation in the pharmacokinetics of the immunosuppressive agents cyclosporine (INN, ciclosporin) and tacrolimus may result from differences in the activity of cytochrome P4503A (CYP3A). The erythromycin breath test is an in vivo assay of hepatic CYP3A activity, but the method has never been directly validated. The aim of the study was to investigate whether an early postoperative erythromycin breath test correlated with the hepatic CYP3A protein level and catalytic activity in liver transplant recipients. METHODS: In 18 liver transplant recipients, the erythromycin breath test was performed within 2 hours after transplantation. A graft biopsy was obtained during surgery and analyzed for the CYP3A protein level by Western blotting and for CYP3A activity with erythromycin demethylation and testosterone 6beta- hydroxylation assays. RESULTS: The erythromycin breath test values ranged from 0.14% to 1.65% of carbon 14 per hour, and the CYP3A protein level ranged from 732 to 7822 as measured by optical density. The in vitro catalytic activity determined by the erythromycin demethylation assay ranged from 94 to 902 disintegrations per minute per 5 minutes per milligram of protein, and the activity determined by testosterone 6beta-hydroxylation ranged from 0.030 to 0.627 nmol per minute per milligram of protein. Significant correlation was demonstrated between the erythromycin breath test and both the erythromycin demethylation (Spearman correlation coefficient: R = 0.76, R (2) = 0.57; P =.0004) and the testosterone 6beta-hydroxylation (Spearman correlation coefficient: R = 0.79, R (2) = 0.63; P =.0001) assays. The erythromycin breath test also correlated with the CYP3A protein level (Spearman correlation coefficient: R = 0.60, R (2) = 0.36; P =.01). CONCLUSION: Our data support the erythromycin breath test as a specific in vivo assay of CYP3A activity in humans. The test is applicable in liver transplant recipients in the early postoperative phase. Future studies should evaluate the clinical usefulness of an early postoperative erythromycin breath test as a predictor of cyclosporine-tacrolimus pharmacokinetics in liver transplantation.

Adolescent↗
PubMed2000

Ephrin-B2 is a candidate ligand for the Eph receptor, EphB6.

No ligand has hitherto been designated for the Eph receptor tyrosine kinase family member, EphB6. Here, expression of an EphB6 ligand in the pro-B leukemic cell line, Reh, is demonstrated by binding of soluble EphB6-Fc fusion protein to the Reh cells. The ligand belongs to the subgroup of membrane spanning ligands, as suggested by the fact that phosphatidylinositol-specific phospholipase C treatment did not abrogate binding of EphB6-Fc. Two transmembrane Eph receptor ligands, ephrin-B1 and ephrin-B2, were identified in Reh cells. Analysis of EphB6-Fc fusion protein binding to ephrin-B1 or ephrin-B2 transfected COS cells revealed a high-affinity saturable binding between EphB6-Fc and ephrin-B2, but not with ephrin-B1. In mice, EphB6 has previously been shown to be expressed in thymus. Here, we show expression of EphB6 in human thymus, as well as the expression of ephrin-B2 in both human and mouse thymus. We conclude that ephrin-B2 may be a physiological ligand for the EphB6 receptor.

Animals↗
PubMed2000

Large expansion of the ATTCT pentanucleotide repeat in spinocerebellar ataxia type 10.

Spinocerebellar ataxia type 10 (SCA10; MIM 603516; refs 1,2) is an autosomal dominant disorder characterized by cerebellar ataxia and seizures. The gene SCA10 maps to a 3.8-cM interval on human chromosome 22q13-qter (refs 1,2). Because several other SCA subtypes show trinucleotide repeat expansions, we examined microsatellites in this region. We found an expansion of a pentanucleotide (ATTCT) repeat in intron 9 of SCA10 in all patients in five Mexican SCA10 families. There was an inverse correlation between the expansion size, up to 22.5 kb larger than the normal allele, and the age of onset (r2=0.34, P=0.018). Analysis of 562 chromosomes from unaffected individuals of various ethnic origins (including 242 chromosomes from Mexican persons) showed a range of 10 to 22 ATTCT repeats with no evidence of expansions. Our data indicate that the new SCA10 intronic ATTCT pentanucleotide repeat in SCA10 patients is unstable and represents the largest microsatellite expansion found so far in the human genome.

Animals↗
PubMed2000

Huntington disease in children: genotype-phenotype correlation.

Huntington disease is a neurodegenerative disorder of adulthood; however, a subset of early-onset patients exists, representing 1% of all HD patients. We reviewed a population of 155 HD-families to determine the frequency, molecular and clinical characteristics of children with an onset before the age of 10 years. In each case, a neurological evaluation was performed as well as molecular detection of the expanded CAG triplet in the affected child and both parents. The family history was also reviewed and updated. Seven children (1.92%) had onset of symptoms before the age of 10, two of them were dead by the time of the study. Large CAG expansions with intergenerational instability were identified, and in one case the child's allele was almost three times larger than the allele of the asymptomatic transmitting father, a situation reported only once before. Clinically, they showed preponderance of rigidity, seizures, learning disabilities and a rapid course of the disease. We attempted to use UHDRS. However, consistent results could not be obtained, suggesting that the scale should be revised for use in juvenile cases. HD should be considered in the differential diagnosis of neurodegenerative diseases in children, even in the absence of a positive family history.

Alleles↗
PubMed2000

Interference of cerebral near-infrared oximetry in patients with icterus.

UNLABELLED: Near-infrared spectrophotometry assesses cerebral oxygen saturation (ScO(2)) based on the absorption spectra of oxygenated and deoxygenated hemoglobin and the translucency of biological tissue in the near-infrared band. In patients with icterus, however, bilirubin can potentially hinder cerebral oximetry. In 48 patients undergoing orthotopic liver transplantation, we related total plasma bilirubin to ScO(2) as determined from spectrophotometry with wavelengths of 733 and 809 nm. Before surgery, ScO(2) was 59% (15%-78%) (median with range) and bilirubin was 71 (6-619) micromol/L with a negative correlation (r = -0.72; P < 0.05). The 95% prediction interval included the lowest measurable ScO(2) of 15% at a bilirubin level of 370 micromol/L. During reperfusion of the grafted liver, the ScO(2) increased by 7% (-8% to 17%) (P < 0.05), and bilirubin did not influence this increase. In one patient, the ScO(2) remained below 15% despite a decrease in bilirubin from 619 to 125 micromol/L, suggesting that tissue pigmentation deposits also absorb light. In conclusion, bilirubin dampens the spectrophotometry-determined cerebral oxygen saturation at 733 and 809 nm. A bilirubin level of 370 micromol/L, tissue pigment deposits, or both, may render determination of cerebral oxygen saturation impossible. Even at high bilirubin values, changes in cerebral perfusion may be visible. IMPLICATIONS: In 48 patients undergoing liver transplantation, the interference of icterus on cerebral oximetry by near-infrared light was investigated. Bilirubin absorbed the near-infrared light and lowered the measured cerebral oxygen saturation. Even at high bilirubin values, changes in cerebral oxygenation, as seen during reperfusion of the grafted liver, may be visible.

Adolescent↗
PubMed1999

Cerebrovascular metabolic autoregulation is impaired during liver transplantation.

BACKGROUND: We determined whether the coupling between cerebral blood flow (CBF) and oxygen metabolism (CMRO2) is preserved during liver transplantation. Because of cerebrovascular dilatation, we hypothesized that cerebral metabolic autoregulation is impaired, because CBF becomes uncoupled from CMRO2 during the reperfusion phase of the operation. MATERIALS AND METHODS: In a prospective study, 13 patients (8 women, median age 46, range 21-6) with liver failure (10 with end-stage chronic liver disease and 3 with acute liver failure) were enrolled. Catheters were placed in a femoral artery and in the internal jugular vein for calculation of the cerebral arteriovenous oxygen content difference (AVDO2). CBF was recorded by the 133Xenon injection technique, and by transcranial Doppler sonography determined mean flow velocity (Vmean) in the middle cerebral artery. The CMRO2 was calculated as the AVDO2 times CBF and the cerebrovascular resistance (CVR) as the mean arterial pressure to CBF ratio. An index of large cerebral artery diameter was expressed by the CBF to Vmean ratio. RESULTS: From induction of anesthesia to the anhepatic period, CBF decreased from a median of 47 (interquartiles 31-55) to 41 (37-48) ml 100 g(-1) min(-1), whereas the CMRO2 remained unchanged (1.3 [0.9-2.5] vs. 1.7 [0.9-2.3] ml 100 g(-1) min(-1)). In the reperfusion phase, the CBF increased to 51 (45-54) ml 100 g(-1) min(-1), whereas the CMRO2 remained unchanged at 1.1 (1.0-2.5) ml 100 g(-1) min(-1). The CVR decreased from 2.0 mm Hg (1.4-2.1) to 1.4 (1.1-1.8) mm Hg(-1) min 100 g ml. In the anhepatic phase, mean arterial pressure decreased from 92 mm Hg (84-98) to 85 (80-92) mm Hg and at reperfusion it was 80 (71-105) mm Hg. From the anhepatic to the reperfusion phase, the CBF increased 7% (0 to 26) for each mm Hg concomitant increase in PaCO2. The CBF to Vmean ratio remained stable (1.0 [0.8-1.2] vs. 0.9 [0.7-1.1] ml 100 g(-1) min(-1) cm(-1) sec). CONCLUSION: During the reperfusion phase of liver transplantations, cerebrovascular dilatation uncouples cerebral oxidative metabolism from blood flow. The increase in CBF is beyond what can be explained by changes in arterial carbon dioxide tension and arterial pressure.

Adult↗
PubMed1999

A randomized trial of risperidone, placebo, and haloperidol for behavioral symptoms of dementia.

OBJECTIVE: To compare effects of risperidone with placebo (efficacy and tolerability) and haloperidol (tolerability) for treating demented patients with aggression and other behavioral symptoms. METHODS: A 13-week double-blind study involving 344 patients with dementia randomly assigned to receive placebo or flexible doses (0.5 to 4 mg/d) of risperidone or haloperidol. Behavioral symptoms were assessed by the Behavior Pathology in Alzheimer's Disease Rating Scale (BEHAVE-AD), the Cohen-Mansfield Agitation Inventory (CMAI), and the Clinical Global Impression (CGI) scale. Tolerability assessments included the Extrapyramidal Symptom Rating Scale, sedation levels, Functional Assessment Staging, Mini-Mental State Examination, and incidence of adverse events. RESULTS: The mean dose at endpoint was 1.1 mg/d of risperidone and 1.2 mg/d of haloperidol. Although not significant, a higher percentage of patients receiving risperidone than those receiving placebo showed clinical improvement (> or =30% reduction from baseline to endpoint in BEHAVE-AD total score) at endpoint and week 12. Reductions in the BEHAVE-AD total score were significantly greater with risperidone than with placebo at week 12. In a further analysis of aggression, the most dominant symptom in these patients, BEHAVE-AD and CMAI aggression cluster scores were significantly reduced compared with placebo at endpoint and week 12. CGI scores were also significantly reduced at endpoint and week 12. Severity of extrapyramidal symptoms with risperidone did not differ significantly from that of placebo and was less than that of haloperidol. A post hoc analysis showed significantly greater reductions in the BEHAVE-AD aggressiveness score with risperidone than haloperidol at week 12. CONCLUSION: Low-dose risperidone (mean 1.1 mg/d) was well tolerated and associated with reductions in the severity and frequency of behavioral symptoms, particularly aggression, in elderly patients with dementia.

Aged↗
PubMed1999

Preserved arterial flow secures hepatic oxygenation during haemorrhage in the pig.

1. This study examined the extent of liver perfusion and its oxygenation during progressive haemorrhage. We examined hepatic arterial flow and hepatic oxygenation following the reduced portal flow during haemorrhage in 18 pigs. The hepatic surface oxygenation was assessed by near-infrared spectroscopy and the hepatic metabolism of oxygen, lactate and catecholamines determined the adequacy of the hepatic flow. 2. Stepwise haemorrhage until circulatory collapse resulted in proportional reductions in cardiac output and in arterial, central venous and pulmonary wedge pressures. While heart rate increased, pulmonary arterial pressure remained stable. In addition, renal blood flow decreased, renal vascular resistance increased and there was elevated noradrenaline spill-over. Further, renal surface oxygenation was lowered from the onset of haemorrhage. 3. Similarly, the portal blood flow was reduced in response to haemorrhage, and, as for the renal flow, the reduced splanchnic blood flow was associated with an elevated noradrenaline spill-over. In contrast, hepatic arterial blood flow was only slightly reduced by haemorrhage, and surface oxygenation did not change. The hepatic oxygen uptake was maintained until the blood loss represented more than 30 % of the estimated blood volume. At 30 % reduced blood volume, hepatic catecholamine uptake was reduced, and the lactate uptake approached zero. 4. Subsequent reduction of cardiac output and portal blood flow elicited a selective dilatation of the hepatic arterial vascular bed. Due to this dilatation liver blood flow and hepatic cell oxygenation and metabolism were preserved prior to circulatory collapse.

Animals↗