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Biomedical subjects

J Lange

Publications and source records attributed to J Lange.

At least 19 recordsLinked to original sources

Radiofrequency ablation permits an effective treatment for colorectal liver metastasis.

BACKGROUND: Radiofrequency ablation (RFA) has become an important adjunct to modern liver surgery. However, scant knowledge on long-term outcome of RFA for colorectal liver metastasis is available, nowadays. METHODS: This is a prospective clinical study of patients with liver metastasis of colorectal cancer who were treated by RFA between April 1, 1998, and November 30, 2004. Forty-seven patients with 147 liver metastases were treated with RFA in a total of 70 interventions. A metastasis resection was not feasible in 80% of the interventions. All the patients were followed up at regular intervals with contrast-enhanced computed tomography (CT) and laboratory tests including carcinoembryonic antigen (CEA). RESULTS: No RFA-related mortality occurred. The median follow-up time after the diagnosis of liver metastasis was 33 months. The RFA-related morbidity was 7%. After the RFA, the expected median overall survival rate is, to date, 39 months. Overall survival rates at 1, 2 and 3 years were 88%, 80% and 57%, respectively. Local recurrence rates reached 8.8% overall and 1.6% for metastasis smaller than 3cm in diameter. No local recurrence occurred for metastasis smaller than 3cm in diameter if treated with the newest RFA device. CONCLUSIONS: Excellent local tumour control was achieved with radiofrequency ablation of small liver metastasis. The expected overall survival rate of patients with RFA for unresectable or non-resected colorectal liver metastasis improved in comparison with the survival rate reported following the natural course (best supportive care) or chemotherapy. The low local recurrence rate of metastases of less than 3cm challenges the results obtained by the more invasive treatment of conventional liver surgery.

Adult↗

Metabolism of tibolone and its metabolites in uterine and vaginal tissue of rat and human origin.

In postmenopausal women, tibolone shows clear tissue differences in its stimulatory effects on the vagina and uterus. In rats, however, it has stimulatory effects on both tissues, with a different, more estrogenic, effect on the uterus than in humans. This may be due to differences in local metabolism. Therefore, in the present study, the metabolism of tibolone was analyzed in incubations of uterine and vaginal tissue from postmenopausal women and ovariectomized rats using radiolabeled tibolone in order to understand the tissue- and species-specific metabolism. In the rat, tibolone (50 nM) was mainly 3alpha-reduced to the estrogenic 3alpha-OH-tibolone in the uterus and vagina. The 3beta-OH tibolone can be isomerized to 3alpha-OH-tibolone with tibolone as intermediate. In contrast, in the same tissues from postmenopausal women, the progestagenic Delta4-isomer and estrogenic 3beta-OH-tibolone were the major metabolites of tibolone. The formation of the Delta4-isomer was higher in uterine tissue. The 3beta-hydroxysteroid dehydrogenase (HSD) inhibitor epostane had no effect on tibolone metabolism in human uterine and vaginal tissue microsomes and HEK293 cells expressing the human 3beta-HSD types 1 and 2 isoforms did not metabolize tibolone. Moreover, the 3beta-reduction of tibolone to 3beta-OH-tibolone was NADPH dependent, while the isomerization of tibolone to the Delta4-isomer did not require a cofactor. It was therefore concluded that human 3beta-HSD isoforms are not involved in the metabolism of tibolone, and that the 3beta-reduction and the Delta5-10 to Delta4 isomerization may be catalyzed by different enzymes. In conclusion, we showed that, in hormone therapy target tissues of the rat as compared with the human, different metabolic pathways for tibolone exist and therefore result in metabolites with different pharmacological properties. The rat is therefore a poor model to predict the effects of tibolone on the uterus in postmenopausal women.

Aged↗

[Correlation between sex, intrauterine position and familial predisposition and neonatal hip ultrasound results].

AIM: To correlate findings of hip ultrasound on day 4-10 of life with sex, intrauterine position and a positive family history for congenital hip anomalies. METHODS: The SNiP-study ( Survey of Neonates In Pommerania) registered 2256 neonates (2030 term, 226 preterm) between May 2002 and March 2004. Hip ultrasound results of 1043 term and since October 2003 33 preterm neonates were analysed. Time of ultrasound was day 4-10 after birth. Preterm neonates were examined when reaching their corrected term gestational age. Ultrasound was applied with a 7.5 MHz linear scanner and results were classified according to Graf. Chi-square and Fishers exact test were used for statistical analysis. RESULTS: 4.9 % of the screened hips were classified as IIc or higher, 3.1 % were unilateral and 1.7 % bilateral. Incidence was significantly higher (p < 0.023) in females (6.6 %) than in males (3.2 %). There was no significant difference in intrauterine position or positive family history for hip anomalies with 3.7 % for mothers, 1.2 % of fathers and 2.4 % of siblings positive. There was a higher incidence for congenital hip dysplasia in preterms with 6.1 %, which is not significant due to the limited number. DISCUSSION: Current screening methods miss up to 18 % of newborns with severe hip dysplasia. We were able to demonstrate that screening for congenital hip dysplasia with ultrasound is a diagnostic tool even during the first days of life. There is a significantly higher incidence of congenital hip dysplasia in females, but in contrast to other studies we found no significant difference in intrauterine position or familial history. Earlier diagnosis and therapy on the base of relevant risk factors might correspond with an improved prognosis and outcome. Further studies are warranted to evaluate the significance in preterm neonates.

Female↗

[Results of SaluCartilage implantation for stage IV chondral defects in the knee joint area].

AIM OF STUDY: This prospective report presents SaluCartilage hydrogel implants, an alternative therapy option in the treatment of chondral defects. METHODS: For the prospective study between October 2002 and July 2003, 18 patients suffering from stage IV chondral defects received 49 hydrogel implants and were subsequently examined by means of clinical, radiological, and magnetic resonance imaging assessment. The knee function was classified using the McDermott score. RESULTS: The average McDermott score was improved to 75 points (p<0.05) after 3 months postoperatively and to 80 points (p<0.05) 6 months postoperatively, but after 12 months it decreased to 69 points. After 3 and 6 months, the MRI showed in all patients that there was fluid around the hydrogel implants without dislocation. After 12 months postoperatively the hydrogel implants had been destroyed in two patients. CONCLUSION: The short-term results showed subjective and objective improvement of the medical conditions probably because of the placeholder function. This alternative should be critically discussed because of the inadequate connection to the bone with risk of dislocation.

Arthroplasty, Replacement, Knee↗

Lack of detectable alterations in immune responses during sublingual immunotherapy in children with seasonal allergic rhinoconjunctivitis to grass pollen.

BACKGROUND: Recent work indicates that subcutaneous specific immunotherapy induces specific T-cell anergy, a shift in the TH1/TH2 ratio, and antibody production in favor of IgG4. There are few data on sublingual immunotherapy (SLIT), especially in children. METHODS: We assessed the proliferation of peripheral blood mononuclear cells ((3)H-thymidine incorporation) and secretion of interleukin (IL)-4, interferon (IFN)gamma and IL-5 (ELISA) after in vitro stimulation with allergen or phytohemagglutinin (PHA) in 29 children with allergic rhinoconjunctivitis receiving SLIT with grass pollen before, and after 1 and 2 years of treatment in a multicenter placebo-controlled study on the efficacy of the treatment. Further, non-specific intracellular production of IL-4, IL-13, IFNgamma, IL-2, IL-10 and IL-5 (FACS) and serum total and specific IgE and IgG4 (ELISA) were analyzed. RESULTS: Proliferation and IL-4 and IL-5 secretion after stimulation with allergen or PHA did not differ between the groups. In addition, we observed no effect of SLIT on intracellular cytokine production. IFNgamma secretion after allergen coculture was comparable between the groups. Following PHA stimulation, IFNgamma secretion was significantly higher in the SLIT group after 1 year, and a trend was observable already before and after 2 years of treatment, probably due to the inhomogeneity in the groups despite randomization (for age and asthma). No significant changes were observed for sIgE/sIgG4 ratios over time either in or between the groups. CONCLUSION: During 2 years of SLIT in children with a positive effect on rescue medication use, we observed no significant effects on in vitro T-cell immune responses or immunoglobulins. So far, pediatric studies demonstrating stable effects of SLIT on such reactions are missing, probably due to limited effects of SLIT on systemic immunologic reactions.

Administration, Sublingual↗

The 48-week efficacy of once-daily saquinavir/ritonavir in patients with undetectable viral load after 3 years of antiretroviral therapy.

OBJECTIVES: To evaluate the efficacy and safety of once-daily saquinavir-soft-gel-capsules/ritonavir (SQV-SGC/RTV) 1600 mg/100 mg plus dual nucleoside reverse transcriptase inhibitors (NRTIs) in HIV-infected patients with plasma viral load (pVL) <50 HIV-1 RNA copies/mL following 3 years of antiretroviral therapy. METHODS: A total of 69 patients with pVL <50 copies/mL after 162 weeks of antiretroviral treatment started SQV-SGC/RTV 1600 mg/100 mg once-daily while continuing dual NRTIs. Previous treatment consisted of 66 weeks of treatment with a half/full dose of zidovudine (ZDV)/zalcitabine (ddC), followed by 2 years of SQV-SGC twice a day (bid) plus ZDV/lamivudine (3TC) or didanosine (ddI)/stavudine (d4T). Efficacy (pVL), safety and immunological changes (CD4 cell counts) were evaluated after 48 weeks in this open-label, single-arm prospective study. RESULTS: SQV-SGC/RTV once-daily was well tolerated. No patient changed regimens or was lost to follow-up. After 48 weeks, 63 of 69 patients (91%) had pVL <50 copies/mL (five of the six remaining patients had pVL <400 copies/mL, and one patient had an unexplained rise to 39 500 copies/mL, which decreased to <50 copies/mL 12 weeks later). Median CD4 count increased from 534 cells/muL at the start of the SQV-SGC/RTV once-daily treatment to 664 cells/muL (P<0.001). Compared to the preceding 48 weeks on bid SQV-SGC, the CD4 cell count improved significantly on once-daily SQV-SGC/RTV (P<0.001). CONCLUSIONS: These data support the use of SQV-SGC/RTV 1600 mg/100 mg once-daily with two NRTIs as a convenient, safe and cost-saving regimen to maintain viral suppression and CD4 counts for 48 weeks in this preselected cohort on highly active antiretroviral therapy (HAART) with pVL <50 copies/mL. The CD4 count rise may be a result of continued immune reconstitution in patients with well-controlled infection.

Adult↗

Pharmacokinetic study of saquinavir hard gel caps/ritonavir in HIV-1-infected patients: 1600/100 mg once-daily compared with 2000/100 mg once-daily and 1000/100 mg twice-daily.

OBJECTIVES: A pharmacokinetic comparison of three dosing regimens of saquinavir/ritonavir was carried out: 1600/100 mg once-daily with 1000/100 mg twice-daily, and 1600/100 mg once-daily with 2000/100 mg once-daily. METHODS: Twenty patients on saquinavir hard gel caps/ritonavir 1600/100 mg once-daily in combination with two nucleoside reverse transcriptase inhibitors for at least 4 weeks were enrolled and randomized to either saquinavir hard gel caps/ritonavir 1000/100 mg twice-daily or 2000/100 mg once-daily. Two pharmacokinetic curves were plotted, at baseline (day 0) and 7 days after the switch. Plasma concentrations were measured at 0, 2, 4, 6, 8, 10, 12 (and 24 for once-daily dosing) hours after drug intake by validated high-performance liquid chromatographic assay (HPLC). The area under the plasma concentration-time curve (AUC0-24 or AUC0-12), maximum and minimum concentration (Cmax and Cmin) and elimination half-life were calculated using a non-compartmental model. RESULTS: Compared with saquinavir/ritonavir 1600/100 mg once-daily dosing, the saquinavir AUC and Cmin improved significantly when dosed as 1000/100 mg twice-daily (53% and 299%, respectively), and as 2000/100 mg once-daily (71% and 65%, respectively). Low Cmin in three subjects at baseline was corrected after switch to the other dosages. Saquinavir/ritonavir 2000/100 mg once-daily was also associated with a significant increase in saquinavir Cmax (52%) compared with saquinavir/ritonavir 1600/100 mg once-daily. CONCLUSIONS: Saquinavir/ritonavir when dosed as 2000/100 mg once-daily or 1000/100 mg twice-daily achieves higher saquinavir plasma levels compared with saquinavir/ritonavir 1600/100 mg once-daily. Taking the convenience of once-daily dosing into consideration, dosage of 2000/100 mg once-daily may be preferred.

Adult↗

Metabolic disturbances during short exercises in dermatomyositis revealed by real-time functional 31P magnetic resonance spectroscopy.

OBJECTIVE: (31)P magnetic resonance spectroscopy (MRS) is useful for evaluating metabolic disturbances in dermatomyositis (DM). However, short-term alterations of metabolic parameters such as Pi/PCr (inorganic phosphate/phosphocreatine) have not been assessed in detail, although they may reveal insights into the origin of the known long-term changes. We therefore performed real-time functional (31)P MRS to find out if there are characteristic short-term alterations of metabolic dynamics during muscular exercise and if they are of diagnostic relevance. METHODS: MRS measurements were performed on lower calf muscles of 10 DM patients and 18 healthy subjects throughout five short (1 min) cycles of submaximal exercise (50% maximum voluntary contraction). RESULTS: Pi/PCr ratios during exercise increased in patients and controls. They rapidly returned to baseline values in the controls, but both Pi and PCr remained above baseline values in patients and resulted in irregular Pi/PCr ratios. This was true for each individual patient, but resulted in broad variation in individual Pi/PCr values. To compare groups with limited patient numbers, it was therefore more appropriate to use a recovery index, i.e. the quotient of the Pi/PCr ratio during and after exercise, which was independent of individual parameters, such as age and the work/energy cost ratio. CONCLUSION: Evaluation of short-term changes by real-time functional (31)P MRS provides insight into alterations of Pi/PCr ratios and could improve diagnostic parameters in DM.

Adenosine Triphosphate↗

[Medial mobilisation of the left hemicolon].

INTRODUCTION: Laparoscopic surgery of the colon is becoming more and more popular. However, regarding sigmoid resection, controversy remains concerning the extent of mobilisation, particularly regarding the splenic flexure. We developed a technique for anterior resection that meets all surgical standards: the anterior approach. MATERIALS AND METHODS: From October 1999 to March 2001, 50 patients with benign diseases of the colon underwent laparoscopically assisted sigmoid resection. A completely anterior approach for mobilisation of the left hemicolon was used in all cases. Positioning the patients in Trendelenburg position on the extreme right side enabled primary ligation of the inferior mesenteric vein and artery as well as complete mobilisation of the splenic flexure from the middle. A transanal circular stapling device was used to reanastomose the colon 10-12 cm from the anus. RESULTS: There were conversion and complication rates of 10% each, and three patients needed to be reoperated. The median operating time was 180 min. Patients could be dismissed on the 14th postoperative day. CONCLUSION: To establish an operative standard, this technique has so far been used only for benign colon diseases. According to our experience, we think that it meets all oncological standards. Use of this technique in the treatment of malignant diseases seems therefore justified.

Adenoma, Villous↗

A prospective, randomized, double-blind, placebo-controlled multi-centre study on the efficacy and safety of sublingual immunotherapy (SLIT) in children with seasonal allergic rhinoconjunctivitis to grass pollen.

BACKGROUND: Especially in childhood, sublingual immunotherapy (SLIT) could offer advantages over subcutaneous therapy. However, limited data on its efficacy is available. METHODS: In four German centres 97 children (age 3-14 years) with allergic rhinoconjunctivitis to grass pollen were enrolled in a prospective, double-blind trial comparing SLIT (Pangramin SLIT; ALK-SCHERAX, 0.5 microg major allergens, three times per week, 32 months) with placebo. Primary endpoint was a multiple symptom-medication score for changes in seasonal diary entries between the first and third year of the study (SLIT n=39; placebo n=38). RESULTS: The multiple symptom-medication score was significantly reduced by SLIT to 77.3% of the placebo group (P=0.0498). The subsequent analysis of the single endpoints did not reveal significant differences for symptom scores in favour of SLIT (85.1% of placebo group; P=0.22). However, the medication score improved significantly (67.1% of placebo group; P=0.0025). Furthermore, secondary endpoints assessing in vivo immune responses did not differ significantly between the groups. However, retrospective analysis showed some inhomogeneity for clinical and in vitro parameters at the beginning of the study. Allergic side effects with possible relation to the study drug were reported in both groups (SLIT 49%, placebo 27%, P=0.026). CONCLUSION: Our study indicates that SLIT had a positive effect on the reduction of a multiple symptom-medication score, mainly by significantly reducing rescue medication use, but had no significant effect on symptoms alone in children with rhinoconjunctivitis to grass pollen compared with a placebo.

Administration, Sublingual↗

Second-harmonic generation from ellipsoidal silver nanoparticles embedded in silica glass.

Second-harmonic generation of uniformly oriented, ellipsoidal silver nanoparticles in a glass matrix was observed and investigated as a function of incidence angle, light polarization, and spatial arrangement of the particles. The results can be explained by the symmetry of the spatial nanoparticle arrangement and by resonance enhancement that is due to the localized surface plasmons of the particles. Second-harmonic enhancement is observed only in sufficiently thin layers (deltakl < pi); on a sample with two separate layers, strong modulation owing to quasi-phase matching is obtained.

Journal Article↗

Morphological characteristics of sensilla on the female ovipositor of Lype phaeopa (Psychomyiidae; Trichoptera).

An important aspect of the association of Lype phaeopa (Stephens) with submerged wood is the oviposition behavior of adult females, which preferably oviposit their eggs on moist emergent or submerged parts of woody debris with a structured surface. The eggs are commonly deposited in cracks and crevices using the elongated ovipositor. Ovipositor morphology and various sensilla on the tip and along the ovipositor were studied by scanning electron microscopy and their possible function discussed. Structure of these sensilla and pre-oviposition behavior of the females point to a preference for certain oviposition sites on woody debris. This may be a key factor for the distribution and development of the larvae.

Animals↗

High interleukin-13 production by phytohaemagglutinin- and Der p 1-stimulated cord blood mononuclear cells is associated with the subsequent development of atopic dermatitis at the age of 3 years.

OBJECTIVE: The aim of our study was to conduct a prospective investigation into the potential association of cord blood proliferative response and cytokine production in response to various stimuli on the development of atopic dermatitis (AD) at the age of 3 years. METHODS: Cord blood mononuclear cells (CBMC) from 40 healthy term neonates were isolated. The proliferative response of CBMC stimulated with IL-2, betalactoglobulin (BLG) and house dust mite allergen (Der p 1) was assessed by liquid scintillation counting and the stimulation index (SI) was calculated. The cytokines interleukin (IL-)13, interferon (IFN-)gamma, IL-10 and IL-18 in the cell culture supernatants in response to phytohaemagglutinin (PHA), Der p 1 and BLG were measured using the ELISA technique. After 3 years, symptoms of AD were obtained with a questionnaire completed by the parents. RESULTS: We observed significantly higher IL-13 levels in response to PHA in children who subsequently developed symptoms of AD (S: median, 291 pg/mL) compared with asymptomatic children (No-S: 149 pg/mL; P=0.021, Wilcoxon test). Similarly, in response to Der p 1 significantly higher IL-13 levels were observed in symptomatic children (S: 168.6; No-S: 61.6 pg/mL; P=0.0084). In response to BLG, IL-13 levels were 287.2 (S) and 123.6 pg/mL (No-S; P=0.19). No significant differences were found when comparing the IFN-gamma levels in CBMC cultures stimulated with PHA (S: 10.2; No-S: 17.6 IU/L; P=0.78), Der p 1 (S: 307.6; No-S: 616.2 IU/L; P=0.2) or BLG (S: 18; No-S: 28.5 IU/L; P=0.83; Fig. 2). The IL-18 and IL-10 levels and the stimulation index in response to IL-2, BLG and Der p 1 showed no significant difference between children who subsequently developed symptoms of AD and asymptomatic children. CONCLUSION: Our data suggest that enhanced IL-13 levels at birth are associated with the subsequent development of atopic symptoms at the age of 3 years.

Allergens↗

Amelioration of murine colitis by feeding a solution of lysed Escherichia coli.

BACKGROUND: Immune reactivity towards the bacterial intestinal flora plays an important part in the pathogenesis of inflammatory bowel disease. Disease activity can be positively influenced by the administration of living probiotic bacteria. We investigated the effect of soluble bacterial antigens extracted from Escherichia coli (strain Laves) on the disease activity of murine colitis. METHODS: C3H.IL-10-/- and BALB/c mice with dextran sulphate sodium-induced colitis were treated with either a bacterial lysate from E. coli or with a placebo. Mice were monitored and inflammation was assessed by histological scoring, analysis of fecal IL-1beta and measurement of cytokine production by ELISA. T cell proliferation was quantified by 3H-thymidine incorporation. RESULTS: Clinically and histologically, bacterial-lysate-treated mice revealed significantly (P < 0.05) fewer signs of colitis than placebo-treated mice. Fecal IL-1beta and mucosal TNF-alpha and IFN-gamma concentrations were significantly lower (P < 0.05) in verum-treated mice than in the placebo group. Furthermore, lymphocyte proliferation after stimulation with lipopolysaccharide or caecal bacterial antigen was significantly (P < 0.05) reduced in verum-treated mice. CONCLUSION: The use of E. coli lysate is effective in the amelioration of murine colitis. This effect may be due to a decreased Th1 reaction and to an induction of tolerance against bacterial antigens.

Animals↗

The power of simplicity.

Many years of use have confirmed didanosine to be among the most potent of nucleoside analogues. Didanosine's potency has been demonstrated in mono-, dual- and triple-therapy. Didanosine is currently available as a once-daily, enteric-coated tablet, which has reduced gastrointestinal side effects compared with the older, buffered formulation. Once-daily dosing and good tolerability improve adherence, and hence also virological control. The prevalence of phenotypic nucleoside resistance to didanosine is low compared with that to zidovudine, lamivudine and abacavir. At least 6 nucleoside analogue mutations are needed in order for the virus to lose sensitivity to didanosine. Didanosine is effective in patients failing lamivudine therapy who have the M184V mutation. Enteric-coated didanosine is also an important component of early therapy, due to its potency and ease of administration.

Anti-HIV Agents↗

Long-term efficacy of dynamic graciloplasty for fecal incontinence.

PURPOSE: Patients with end-stage fecal incontinence in whom all standard medical and surgical treatment has failed or is not expected to be effective can be treated by dynamic graciloplasty. The aim of this study was to review the long-term efficacy data. METHODS: Success was defined as a greater than 50 percent decrease in the frequency of incontinent episodes. Measured physiologic parameters included enema retention time and the difference in resting and squeezing pressures with and without stimulation. Measured quality-of-life parameters included the Medical Outcomes Study Short Form 36 Health Status Questionnaire, a Fecal Incontinence TyPE Specification, the Zung Self-Rating Depression Scale, the "state" portion of the State-Trait Anxiety Inventory, and the Visual Analog Scale, which were administered at baseline and through follow-up. Independent monitors collected data as part of a multicenter trial for patients who underwent dynamic graciloplasty from May 1993 to November 1999. RESULTS: There were 129 patients entered in the study, 115 of whom met eligibility criteria and were included in the efficacy outcome analysis. Twenty-seven patients entered the study with a preexisting functioning stoma; the remaining 88 patients did not have a functioning stoma at the time of enrollment. Success was achieved in 62 percent of nonstoma patients at 12 months; these results were sustained at 18-month and 24-month follow-up assessments (55 and 56 percent, respectively). The success rate in the stoma patients increased from 37.5 percent (9 of 24 patients) at 12 months to 62 percent (13 of 21 patients) at 18 months and was 43 percent at 24 months (9 of 21 patients), which reflects the increased number of patients whose stomas were closed. Although the measured physiologic continence parameters generally improved, these changes did not correlate with continence outcome. The group of patients (stoma and nonstoma) who underwent dynamic graciloplasty showed statistically significant improvements in quality of life as measured by Medical Outcomes Study Short Form 36 physical function (P = 0.006) and social functioning (P = 0.02) assessment. CONCLUSIONS: Dynamic graciloplasty was successful in the majority of patients with end-stage fecal incontinence. This result was usually achieved by 12 months after surgery in patients who did not have stomas and by 18 months in patients who had stomas at the time of dynamic graciloplasty surgery. These various improvements conferred by dynamic graciloplasty persisted during the two-year follow-up.

Adolescent↗