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Biomedical subjects

M Thorn

Publications and source records attributed to M Thorn.

18 recordsLinked to original sources
PubMed2006

Branching patterns and drainage territories of the middle hepatic vein in computer-simulated right living-donor hepatectomies.

Full right hepatic grafts are most frequently used for adult-to-adult living donor liver transplantation (LDLT). One of the major problems is venous drainage of segments 5 and 8. Thus, this study was designed to provide information on venous drainage of right liver lobes for operation-planning. Fifty-six CT data sets from routine clinical imaging were evaluated retrospectively using a liver operation-planning system. We defined and analyzed venous drainage segments and the impact of anatomic variations of the middle hepatic vein (MHV) on venous outflow from segments 5 and 8. MHV variations led to significant shifts of segment 5 drainage between the middle and right hepatic vein. In cases with the most frequent MHV branching pattern (n = 33), a virtual hepatectomy closely right to the MHV intersected drainage vessels that provided drainage for 30% of the potential graft, not taking into account potential veno-venous shunts. In individuals with inferior MHV branches that extend far into segments 5 and 6 (n = 10), the overall graft volume at risk of impaired venous drainage increased by 5% (p < 0.001). If this is confirmed in clinical trials and correlated with intraoperative findings, the use of liver operation-planning systems would be beneficial to improve overall outcome after right lobe LDLT.

Computer Simulation↗
PubMed2005

[The role of 3-D imaging and computer-based postprocessing for surgery of the liver and pancreas].

Cross-sectional imaging based on navigation and virtual reality planning tools are well-established in the surgical routine in orthopedic surgery and neurosurgery. In various procedures, they have achieved a significant clinical relevance and efficacy and have enhanced the discipline's resection capabilities. In abdominal surgery, however, these tools have gained little attraction so far. Even with the advantage of fast and high resolution cross-sectional liver and pancreas imaging, it remains unclear whether 3D planning and interactive planning tools might increase precision and safety of liver and pancreas surgery. The inability to simply transfer the methodology from orthopedic or neurosurgery is mainly a result of intraoperative organ movements and shifting and corresponding technical difficulties in the on-line applicability of presurgical cross sectional imaging data. For the interactive planning of liver surgery, three systems partly exist in daily routine: HepaVision2 (MeVis GmbH, Bremen), LiverLive (Navidez Ltd, Slovenia) and OrgaNicer (German Cancer Research Center, Heidelberg). All these systems have realized a half- or full-automatic liver-segmentation procedure to visualize liver segments, vessel trees, resected volumes or critical residual organ volumes, either for preoperative planning or intraoperative visualization. Acquisition of data is mainly based on computed tomography. Three-dimensional navigation for intraoperative surgical guidance with ultrasound is part of the clinical testing. There are only few reports about the transfer of the visualization of the pancreas, probably caused by the difficulties with the segmentation routine due to inflammation or organ-exceeding tumor growth. With this paper, we like to evaluate and demonstrate the present status of software planning tools and pathways for future pre- and intraoperative resection planning in liver and pancreas surgery.

Hepatectomy↗
PubMed2005

Phenotypic and functional characterization of clinical grade dendritic cells generated from patients with advanced breast cancer for therapeutic vaccination.

Dendritic cells (DC) are promising candidates for cancer immunotherapy. However, it is not known whether in vitro-generated monocyte-derived DC from cancer patients are altered compared with DC from healthy donors. In a clinical phase I/II study, monocyte-derived DC were generated in vitro utilizing granulocyte macrophage colony-stimulating factor and rh-interleukin-4 (IL-4) and used for cancer immunotherapy. In this study, we tested the effect of various maturation cocktails and performed a comparative evaluation of the DC phenotype and functional characteristics. Polyriboinosinic polyribocytidylic acid (Poly I:C) + tumour necrosis factor-alpha (TNF-alpha) induced significant IL-12 p70 secretion, which was increased after addition of a decoy IL-10 receptor. The lymph node homing chemokine receptor CCR-7 expression was induced by TNF-alpha + IL-1beta + IL-6 + prostaglandin E2 but was not induced by Poly I:C + TNF-alpha. In general, DC from patients had an intermediate maturity phenotype with a significantly higher expression of CD40 and CD54 compared with healthy donors. In vitro analyses showed an unimpaired capacity of the patient-derived DC for antigen-specific (cytomegalovirus, tetanus and keyhole limpet haemocyanin) T-cell stimulation, whereas the allostimulatory capacity of patient-derived DC was significantly decreased. These data suggest that patient-derived DC are more differentiated but are less sensitive to maturation-inducing agents than DC obtained from healthy individuals.

Breast Neoplasms↗
PubMed2003

Immunobiological effects of glucosamine in vitro.

Glucosamine (GlcN) and N-acetyl-d-glucosamine (GlcNAc) were assayed in vitro for their effects on proliferation, cytotoxicity and cytokine secretion in primary and secondary mixed lymphocyte cultures (MLCs). In addition, we studied the effect of GlcN and GlcNAc on the proliferation of purified CD4+ T cells exposed to immobilized anti-CD3 antibody. The present data show that GlcN, but not GlcNAc, inhibits CD4+ T-cell proliferation, the generation of alloreactive cytotoxic T lymphocytes (CTLs) and the secretion of interferon-gamma (IFN-gamma) and interleukin-5 (IL-5) in primary MLC. In secondary T helper-2 (Th2)-polarized MLC, GlcN, but not GlcNAc, inhibits IL-4 and IL-5 secretion, whereas no effect was found on IFN-gamma secretion in Th1-polarized MLC. Dendritic cells treated with GlcN showed a 75-80% decreased capacity for antigen cross-presentation and allostimulation. In cellular bioassays, GlcN was shown to inhibit the stimulatory activity of IL-4 and IL-2, as well as the cytotoxic activity of tumour necrosis factor-alpha (TNF-alpha). In conclusion, GlcN suppresses unprimed T-cell responses by interfering with antigen-presenting cell functions and by a direct inhibitory effect on T-cell proliferation. In addition, GlcN inhibits the secretion of cytokines in antigen-stimulated unprimed T cells and primed Th2-polarized cells.

Adjuvants, Immunologic↗
PubMed2002

The effect of virtual reality and training on liver operation planning.

OBJECTIVE: The three-dimensional relation of a liver tumour to the intrahepatic vascular trees is basis of operation planning in liver surgery. Yet it has not been proven whether 3D reconstruction and further computerised processing will enhance precision of operation planning in liver surgery which has been based on the liver segment classification of Couinaud up to now. DESIGN: Our interdisciplinary group (department of Surgery, German Cancer Research Center and Department of Radiology) has developed a new interactive computer-based quantitative 3D operation planning system for liver surgery which is being introduced into the clinical routine. The system quantifies the organ structures semiautomatically, defines resection planes depending on safety margins and the vascular trees, and presents the data in digital movies as well as in quantitative reports. We conducted a clinical trial to evaluate whether 3D reconstruction will lead to an improved operation planning. Data of 7 virtual patients were presented to a total of 81 surgeons in different levels of training. The tumours had to be assigned to a liver segment and subsequently drawn together with the operation proposals into a liver model. The precision of both was measured quantitatively for each surgeon and stratified concerning 2D and different types of 3D presentations. RESULTS: The 3D anatomy can be visualised in high quality which results in good perception of the third dimension (depth). Tumour assignment to liver segments was significantly correlated to the level of training (p < 0.05). There was a significant increase (p < 0.001) in the precision of tumour localisation by 51% and resection proposal from 2D through 3D reconstructions by 13%-21%. Quantitative differences of the simplified Couinaud's classification of the liver segments compared to the true vascular anatomy of up to 40% were found. CONCLUSION: The impact of individual 3D-reconstruction on surgical planning has been proven to be significant and increases precision quantitatively. The merit of Couinaud's classification may be enhanced by individualisation of the segment borders in future.

Hepatectomy↗
PubMed2001

Evidence of local eosinophil activation and altered mucosal permeability in collagenous colitis.

The local release of the inflammatory mediators eosinophil cationic protein and myeloperoxidase and the permeability marker albumin was studied in collagenous colitis using a new technique for segmental perfusion of the rectum and descending colon. Perfusion of both segments was successful in 19/25 (76%) of patients with collagenous colitis and controls with noninflammatory conditions. The concentration of myeloperoxidase was increased in the perfusion fluids from both segments in only one patient with collagenous colitis and in none of the controls. On the other hand, concentrations of eosinophil cationic protein and albumin in the perfusate from the rectum were significantly increased in collagenous colitis compared with controls, and similar trends were seen in the perfusates from the descending colon. Furthermore, there was a significant correlation between the increased concentrations of eosinophil cationic protein and albumin, indicating a possible relation between eosinophil activation and disturbed mucosal permeability in collagenous colitis.

Adult↗
PubMed2000

The impact of 3-dimensional reconstructions on operation planning in liver surgery.

BACKGROUND: Operation planning in liver surgery depends on the precise understanding of the 3-dimensional (D) relation of the tumor to the intrahepatic vascular trees. To our knowledge, the impact of anatomical 3-D reconstructions on precision in operation planning has not yet been studied. HYPOTHESIS: Three-dimensional reconstruction leads to an improvement of the ability to localize the tumor and an increased precision in operation planning in liver surgery. DESIGN: We developed a new interactive computer-based quantitative 3-D operation planning system for liver surgery, which is being introduced to the clinical routine. To evaluate whether 3-D reconstruction leads to improved operation planning, we conducted a clinical trial. The data sets of 7 virtual patients were presented to a total of 81 surgeons in different levels of training. The tumors had to be assigned to a liver segment and subsequently drawn together with the operation proposal into a given liver model. The precision of the assignment to a liver segment according to Couinaud classification and the operation proposal were measured quantitatively for each surgeon and stratified concerning 2-D and different types of 3-D presentations. RESULTS: The ability of correct tumor assignment to a liver segment was significantly correlated to the level of training (P<.05). Compared with 2-D computed tomography scans, 3-D reconstruction leads to a significant increase of precision in tumor localization by 37%. The target area of the resection proposal was improved by up to 31%. CONCLUSION: Three-dimensional reconstruction leads to a significant improvement of tumor localization ability and to an increased precision of operation planning in liver surgery.

Computer Simulation↗
PubMed2000

N-3 polyunsaturated fatty acids do not affect cytokine response to strenuous exercise.

The aim of the present study was to investigate whether fish oil supplementation was able to modulate the acute-phase response to strenuous exercise. Twenty male runners were randomized to receive supplementation (n = 10) with 6.0 g fish oil daily, containing 3.6 g n-3 polyunsaturated fatty acids (PUFA), for 6 wk or to receive no supplementation (n = 10) before participating in The Copenhagen Marathon 1998. Blood samples were collected before the race, immediately after, and 1.5 and 3 h postexercise. The fatty acid composition in blood mononuclear cells (BMNC) differed between the fish oil-supplemented and the control group, showing incorporation of n-3 PUFA and less arachidonic acid in BMNC in the supplemented group. The plasma levels of tumor necrosis factor-alpha, interleukin-6, and transforming growth factor-beta(1) peaked immediately after the run, the increase being 3-, 92-, and 1.1-fold, respectively, compared with resting samples. The level of interleukin-1 receptor antagonist peaked 1.5 h after exercise, with the increase being 87-fold. However, the cytokine levels did not differ among the two groups. Furthermore, supplementation with fish oil did not influence exercise-induced increases in leucocytes and creatine kinase. In conclusion, 6 wk of fish oil supplementation had no influence on the acute-phase response to strenuous exercise.

Adult↗
PubMed1998

Factors associated with atypical nevi: a population-based study.

We conducted a case-control study to identify factors associated with the presence of clinically atypical nevi. Potential participants were selected, using a two-staged sampling scheme, from a population-based cohort of 50,000 Swedish women who had responded to a previous health survey questionnaire. Of 500 women sampled for study recruitment, 400 (80%) agreed to participate. Study participants underwent a physician-conducted skin examination, which identified 130 women who had at least one clinically atypical nevus (cases) and 270 women without these lesions (controls). The physician-conducted skin examination also assessed women for benign nevus counts; other risk factor information was based upon responses to a health survey questionnaire. We found a strong and highly statistically significant relationship between number of benign nevi and the presence of at least one clinically atypical nevus (P < 0.0001). Women with 100 or more benign nevi had a 26-fold increased likelihood of having an atypical nevus. We noted statistically significant interactions between number of benign nevi and other factors of interest; thus, the results are reported separately for women with low (<50) or high (> or =50) counts of benign nevi. Among women with low counts of benign nevi, the likelihood of having an atypical nevus increased with degree of freckling; there was also a suggested role for early sun exposure. Among women with high counts of benign nevi, difficulty tanning and lack of peeling sunburns between ages 10 and 19 appeared to increase the likelihood of case status; our data also suggested an inverse relationship between parity and atypical nevi in this subgroup.

Adult↗
PubMed1994

Discontinuing antiepileptic drugs in children with epilepsy. A comparison of a six-week and a nine-month taper period.

BACKGROUND: The optimal regimen for discontinuing antiepileptic medications in children with epilepsy is unknown. METHODS: We randomly assigned 149 children to either a six-week or a nine-month period of drug tapering, after which therapy was discontinued. Each group was composed of patients who had been seizure-free for either two or four years before drug tapering was begun. Most patients were receiving one antiepileptic drug; none were taking more than two. The children were evaluated periodically during and after the taper period. Sixteen patients were lost to follow-up before the beginning of the taper period. Proportional-hazards regression analysis was used to assess the risk of seizure recurrence among the remaining 133 patients. RESULTS: Seizures recurred in 53 patients (40 percent). The mean duration of follow-up was 39 months (range, 11 to 105) for the patients who did not have a recurrence of seizures. Neither the length of the taper period (six weeks vs. nine months, P = 0.38) nor the length of time the patients were free of seizures before the taper period was begun (two years vs. four years, P = 0.20) significantly influenced the risk of seizure recurrence. The presence of mental retardation (relative risk, 3.1, 95 percent confidence interval, 1.5 to 6.2) or spikes in the electroencephalogram at the time of tapering (relative risk, 1.9, 95 percent confidence interval, 1.0 to 3.4) increased the risk of seizure recurrence. CONCLUSIONS: The risk of seizure recurrence during drug tapering and after the discontinuation of antiepileptic drug therapy in children with epilepsy is not different whether the medications are tapered over a six-week or a nine-month period.

Adolescent↗
PubMed1993

Randomized trial of dapsone and aerosolized pentamidine for the prophylaxis of Pneumocystis carinii pneumonia and toxoplasmic encephalitis.

PURPOSE: Pneumocystis carinii pneumonia (PCP) and toxoplasmic encephalitis are the most frequent pulmonary and central nervous system opportunistic infections associated with human immunodeficiency virus (HIV) infection. We designed a prospective study to compare the effects of aerosolized pentamidine and dapsone in the prophylaxis of these infections in HIV-infected persons with CD4+ lymphocyte counts less than 250/mm3. PATIENTS AND METHODS: Two hundred seventy-eight patients seropositive for HIV who had acquired immunodeficiency syndrome (AIDS) or advanced AIDS-related complex were randomly assigned to receive intermittent dapsone (100 mg twice weekly) or aerosolized pentamidine (100 mg every 2 weeks). The proportion of patients remaining free of PCP or toxoplasmosis was analyzed with the log-rank test as a function of time, as were the effects of zidovudine or prophylaxis on survival. RESULTS: Dapsone and aerosolized pentamidine demonstrated similar efficacy in the primary and secondary prophylaxis of PCP, with 15 (18%) failures among patients receiving dapsone compared to 15 (14%) among those receiving aerosolized pentamidine (p = 0.4), after a mean length of follow-up of 42 and 44 weeks, respectively. Dapsone was more effective in the primary prophylaxis of toxoplasmic encephalitis, with six toxoplasmic encephalitis events occurring among those receiving aerosolized pentamidine, compared to none among those taking dapsone (p = 0.01). Primary prophylaxis for PCP was more effective than secondary prophylaxis with either therapy. Zidovudine therapy did not prevent PCP yet prolonged the PCP-free interval for those in whom either prophylactic therapy failed. Kaplan-Meier estimates did not show a difference in survival between the patients receiving either therapy, yet zidovudine use was associated with improved survival, independent of race and risk factor (Cox proportional hazards model, p = 0.001). The 1-month survival for patients developing PCP despite prophylaxis was better with those in whom dapsone failed than it was for those in whom aerosolized pentamidine failed (p = 0.08). CONCLUSION: Dapsone is as effective as aerosolized pentamidine in preventing PCP and has the advantage of a lower cost, easier administration, and possibly an additional preventive effect against toxoplasmosis. Zidovudine prolongs the PCP-free interval for patients receiving prophylaxis, regardless of which prophylactic agent is used.

AIDS-Related Opportunistic Infections↗
PubMed1992

Level and diurnal variations of hormones of interest to the cardiovascular system in patients with heart transplants.

The lack of a nocturnal decrease in blood pressure in cyclosporine-treated cardiac transplant recipients may indicate abnormalities in the mechanism(s) responsible for circadian variability in other physiologic parameters such as in circulating hormones. This possibility was addressed through repeated determinations of circulating catecholamines, neuropeptide Y, pancreatic polypeptide, calcitonin gene-related peptide, plasma renin activity, aldosterone, atrial natriuretic factor and cortisol. The results from 10 patients with heart transplants were compared with those of 12 age-matched, healthy control subjects. Both groups were studied during 24-hour supine rest. There was no difference between patients and control subjects in mean levels of catecholamines, neuropeptide Y, pancreatic polypeptide and aldosterone. Patients had higher levels (+/- SD) of plasma renin activity (6.4 +/- 1.3 vs 2.6 +/- 0.4 ng/ml/hour, p less than 0.001), calcitonin gene-related peptide (47.7 +/- 9.9 vs 33.3 +/- 5.7 pmol/liter, p less than 0.01) and atrial natriuretic factor (93.0 +/- 56.7 vs 20.7 +/- 8.9 pg/ml, p less than 0.001) than control subjects, respectively. Cortisol was not detected in patients. Abnormal diurnal profiles in patients were found for calcitonin gene-related peptide, aldosterone and atrial natriuretic factor, and for pancreatic polypeptide, together with decreased levels, in patients with greater than 6 months follow-up. Except for hormones reflecting sympathetic nervous activity, all hormonal systems studied showed abnormalities in level or circadian rhythmicity, or both. The pancreatic polypeptide results suggest that parasympathetic neuropathy could develop in cyclosporine-treated heart transplant recipients.

Adrenal Cortex Hormones↗
PubMedDate not supplied

Design and synthesis of a maximally diverse and druglike screening library using REM resin methodology.

A 3042 compound screening library was synthesized using a combination of two solid-phase technologies: REM resin methodology and Lewis acid promoted aminolysis. The exclusivity and structural diversity of the library were enhanced by using a highly divergent synthetic strategy involving 13 different scaffolds (9 of which were custom-made), five different types of resin-bound phenol derivatization chemistry (Mitsunobu, Suzuki, acylation, sulfonylation, and carbamoylation), and three different cleavage strategies (Hofmann elimination, AlCl(3)-promoted aminolysis, base-promoted esterolysis). This is the first example of a solid-phase Suzuki coupling involving a resin-bound aryl triflate being used for library synthesis. Computational analysis suggested that the compounds are likely to have favorable properties for CNS penetration. Analysis of the library by HPLC and MS suggested at least 90% of the sampled members were present in an average purity of approximately 70%. Encouragingly, hits have been identified from high-throughput screening of this library, such as compound 6, which has an affinity of 1.02 microM for the GlyT(2) transporter.

Animals↗
PubMedDate not supplied

The effect of chemical dependency on pain perception in persons with AIDS.

A sample of persons with AIDS (N = 71) was drawn from two tertiary care centers and one group residence. Chemical dependence was measured by the Michigan Alcoholism Screening Test (MAST) and the Drug and Alcohol Screening Test (DAST), and the perception of pain was then measured with the Wisconsin Brief Pain Inventory. The hypothesis that the groups would demonstrate a significantly different perception of pain was not supported. Self-report of drug and alcohol use did not correlate well with scores on the MAST and DAST, indicating that these instruments may not measure chemical dependence in persons with AIDS. On scales of zero to 10, mean scores reflecting pain intensity averaged 5.1 and scores reflecting pain's interference with seven aspects of daily life averaged 5.98.

Acquired Immunodeficiency Syndrome↗