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Biomedical subjects

J Lange

Publications and source records attributed to J Lange.

At least 37 records · Page 2Linked to original sources
PubMed2002

Dopaminergic and opioidergic regulation of gonadotropin and prolactin release in stallions.

In the non-breeding season, LH release is reduced via dopaminergic systems in the ram. On the other hand, our previous studies demonstrated an opioidergic inhibition of LH release in stallions outside the breeding season. Thus, in the present study we investigated the dopaminergic regulation of LH and prolactin secretion in stallions, considering interactions between dopamine and opioids. To achieve this, stallions (n=8) were treated with the dopamine antagonist sulpiride (0.6 mg/kg), the opioid antagonist naloxone (0.5 mg/kg), sulpiride plus naloxone or saline in December, March and June. Two hours after the respective treatments, they received a GnRH agonist. Sulpiride induced a significant prolactin release which was most pronounced in December, indicating seasonal variations in the inhibition of prolactin secretion by dopaminergic systems. Prolactin concentrations were not changed by naloxone. Neither during nor outside the breeding season, a dopaminergic regulation of LH release could be demonstrated. In contrast, naloxone caused a significant (p < 0.05) LH release, confirming an opioidergic inhibition of LH release. In conclusion, opioidergic regulation of LH and dopaminergic inhibition of prolactin secretion undergo seasonal changes. Neither during nor outside the breeding season, dopaminergic effects on LH release exist in the stallion.

Animals↗
PubMed2002

[Endometrial carcinoma using GnRH analogues therapy in endometriosis].

Endometriosis affects a 10 % of women during their reproductive years. Unequoral statistics concerning the incidence of adenomyosis are not available although a combined occurrence of both diseases is found in a 20 % of cases. The risk that malignancy arises from endometrioid tissue typical for endometriosis is between a 0.3-1 %. 75 % of these malignancies are ovarian cancer in conjunction with pre-existing ovarian endometriosis; less frequently extraovarian malignancies are found. The development of malignancy of adenomyosis is very rarely reported. In this report we present the case of a 35 year old patient who suffered from both, endometriosis and adenomyosis and who underwent a therapy using GnRH analogues. After five months and before the completion of the therapy a hysterectomy with conservation of the ovaries was performed at the request of the patient (carcinophobia). The histology confirmed the diagnosis of adenomyosis and demonstrated the unexpected finding of an endometrium carcinoma. This latter arose from a complex atypical hyperplasia surrounded by hypoplastic endometrium. There is some evidence that suggests a slightly elevated risk of breast and ovarian cancer as well as haematological malignancies amongst patients with endometriosis. However, there does not appear to be an increased risk of endometrial carcinoma. Adipositas leads to an increased risk for the development of endometrial carcinoma due to the increased conversion of testosterone to estrone in fat. The peripheral synthesis of estrone is unaffected by GnRHa-therapy. A progesterone containing HRT should be added to a GnRHa-therapy in overweight patients to prevent the development of endometrial hyperplasia and/or carcinoma. In conclusion a careful indication has to be made for GnRHa-therapy in overweight patients and before and during the therapy high resolution ultrasound scan should be performed to evaluate the endometrium in those patients.

Adult↗
PubMed2001

[Pre- and postoperative transaminase changes within the scope of gastric banding in morbid obesity].

UNLABELLED: 20-30% of obese patients without concomitant liver disease show elevated liver tests (ALAT, ASAT, GGT) which are known to normalize after weight reduction. Little is known about the impact of gastric banding on elevated liver enzymes. We investigated the role of gastric banding on weight reduction and liver enzymes in a cohort of patients with morbid obesity. 198 obese patients (166 female, 32 male: median age 37 [19-65] years) with BMI 46 kg/m2 were assessed prior to gastric banding and 6/12 months postoperative for BMI, ALAT, ASAT, GGT respectively. Specific liver diseases were excluded. 37 patients (18.7%) had elevated liver enzymes (ALAT 14.1%, ASAT 9.6%, GGT 6.6%) preoperatively. ALAT and ASAT returned to normal in all patients postoperatively (p < 0.01). In 14 patients with significant ALAT-elevation (i.e. > 10% above normal) we found a correlation between postoperative fall of ALAT and reduction of BMI within 12 month (r = 0.4998; p < 0.05). CONCLUSION: 18.7% of morbid obese patients (BMI 46 kg/m2) have elevated liver enzymes prior to laparoscopic gastric banding. The normalisation of elevated liver enzymes correlates to the extent of weight reduction after gastric banding. Our data show reversible liver enzyme abnormalities, correlating to the degree of obesity.

Adult↗
PubMed2001

Antiretroviral treatment simplification with nevirapine in protease inhibitor-experienced patients with hiv-associated lipodystrophy: 1-year prospective follow-up of a multicenter, randomized, controlled study.

BACKGROUND: Simpler and less toxic antiretroviral strategies are needed to maximize treatment compliance without sacrificing potency, at least for drug-experienced HIV-infected patients currently on regimens containing protease inhibitors (PIs). Small nonrandomized studies have suggested a beneficial role of PI-sparing regimens on lipodystrophy. OBJECTIVES: To assess the virologic, immunologic, and clinical benefit of switching the PI to nevirapine in patients with HIV-associated lipodystrophy and sustained viral suppression before entry in the study. DESIGN: Open-labeled, prospective, randomized, multicenter study. SETTING: Seven reference inpatient centers for HIV/AIDS in Spain. PATIENTS: One hundred six HIV-infected adults with clinically evident lipodystrophy who sustained HIV-RNA suppression for at least 6 months with PI-containing antiretroviral combinations. INTERVENTION: Replacement of the PI with nevirapine during 48 weeks (Group A) versus continuing the prior PI (Group B). MEASUREMENTS: Several virologic and immunologic analyses, standard and specific biochemical tests, and anthropometric and dual X-ray absorptiometry measurements. RESULTS: At week 48, an HIV-1 RNA level <400 copies/ml was maintained in 79% and 77% of patients in Groups A and B, respectively, whereas 74% and 72% of patients had viral load levels <50 copies/ml. Absolute CD4+ counts significantly increased in both groups compared with baseline values, and a significant decrease in CD38+CD8+ cells was observed in Group A (p <.01) but not in group B. Overall, no significant changes in anthropometric or body shape measurements were found after 48 weeks. Fasting total cholesterol and triglyceride levels decreased in Group A (but not in Group B) compared with baseline values (p <.05), although no significant differences were seen between groups at the end of the study. Subjects in Group A reported a better quality of life (QOL) index than controls (p <.001), with the main reason reported being the greater simplicity of the new drug regimen. CONCLUSIONS: Protease inhibitor-sparing regimens, including nevirapine, seem to be an effective alternative for PI-experienced patients. Nevirapine-based triple therapies allow maintained control of HIV-1 RNA levels and improve the immunologic response at 48 weeks of follow-up in patients with prior sustained virologic suppression. The switch to nevirapine significantly improved the lipidic profile in Group A, although there were no differences between groups at the end of the study. Additionally, no significant changes were seen in terms of lipodystrophy-related body shape changes 1 year after the PI substitution. Finally, nevirapine-containing regimens have a simpler dosing schedule, and this facilitates high adherence and improves QOL.

Adult↗
PubMed2001

10 Swiss kindreds with multiple endocrine neoplasia type 1: assessment of screening methods.

PRINCIPLES: Multiple endocrine neoplasia type 1 (MEN1) is an autosomal dominant disease characterised by the combined occurrence of tumours of the parathyroid glands, the enteropancreatic neuroendocrine system and the anterior pituitary gland. The genetic defect has been mapped to the long arm of chromosome 11q13, and the MEN1-gene was recently identified by positional cloning. Genetic screening for MEN1 germline mutations allows the identification of gene carriers in affected kindreds. Biochemical and radiological screening for MEN1 tumours allows an earlier diagnosis and treatment, and, thus may reduce morbidity and mortality. Since there is no consensus about the frequency and the extent of the necessary screening investigations, evaluation of proposed screening programs is of importance. METHODS: The aims of our study were to identify the MEN1-gene mutations and to detect the gene-carriers in 10 Swiss MEN1 families, as well as to assess biochemical and radiological screening methods. The study included 45 members from 10 MEN1 families. RESULTS: Every family had a different type of MEN1-gene mutation. Thirty out of 45 family members were gene mutation carriers. Twenty-two MEN1-gene carriers had typical MEN1 tumours: parathyroid, enteropancreatic and pituitary tumours were found in 21, 14 and 1 patients, respectively. Applying a defined screening program the following manifestations in asymptomatic MEN1-gene carriers were detected: 9 primary hyperparathyroidism, 3 nonfunctioning pancreatic tumours, 1 gastrinoma, 1 nonfunctioning microadenoma of the pituitary and 1 macronodular adrenal hyperplasia. CONCLUSIONS: The genetic screening facilitates the identification of individuals who carry MEN1-gene mutations, and allows one to exclude non-mutant gene carriers from further investigations. The prospective biochemical and radiological screening of gene mutation carriers allows the earlier detection of MEN1-associated tumours. Therefore, it might be expected that morbidity and mortality of the MEN1 could be reduced.

Adolescent↗
PubMed2001

Electron self-exchange kinetics in two average-valence dicopper cryptates.

Electron self-exchange rates, reported for two average-valence dicopper cryptates are, at around 10(5) M-1 s-1, at the high end of the range for small-molecule model compounds. The cross-exchange reaction rate, and those for oxidation with [Co(ox)3]3-, are consistent with an outer-sphere reaction mechanism. Despite the necessity for copper-copper bond making and breaking in the course of redox for one of the cryptates, the self-exchange rate is not decreased relative to the other cryptate, showing that this step is not rate limiting.

Bridged Bicyclo Compounds, Heterocyclic↗
PubMed2001

A novel, automated method of temperature cycling to produce cryoprecipitate.

BACKGROUND: Cryoprecipitate continues to find wide application in transfusion practice. Current AABB standards call for a minimum of 80 units (U) of factor VIII and 150 mg of fibrinogen per bag of cryoprecipitate. However, individual cryoprecipitates can vary greatly in content, with as many as 20 different factors known to affect the yield. STUDY DESIGN AND METHODS: Plasma was processed in a new, rapid, automated device (CryoSeal, Thermogenesis) with computer-controlled temperature cycling to produce cryoprecipitate. RESULTS: In repeat runs (n = 20), the automated procedure yielded a product containing 184 mg of fibrinogen and 158 U of factor VIII in 55 minutes. Additional studies using plasma pools to compare the quality of the machine-generated products to those of traditionally prepared cryoprecipitate showed comparative recoveries of 182 and 187 mg of fibrinogen and 172.1 and 129.7 U of factor VIII and no significant difference in the levels of plasminogen, protein C, or protein S. CONCLUSION: The new system offers an automated method of cryoprecipitate production in which the steps involved in temperature cycling are initiated sequentially, producing within 1 hour a preparation that is equivalent to standard cryoprecipitate.

Cryopreservation↗
PubMed2001

[The impact of pregnancy-prolonging management on maternal and neonatal morbidity in HELLP syndrome].

OBJECTIVE: Until recently, delivery immediately after diagnosing HELLP syndrome was recommended due to the life-threatening risk to mother and child. Prolongation at least until lung maturation is being increasingly considered because of the high rate of premature births characterized by extreme immaturity. We investigated the influence of the time of delivery on maternal and neonatal morbidity at a gestational age of less than 34 + 0 weeks of pregnancy. - MATERIAL AND METHODS: The disease course was reevaluated in 37 patients who developed HELLP syndrome (thrombocytes < 100 000/microl, transaminase > 70 U/l, haptoglobin < 0.5 g/l) between 1994 and 1999. An attempt was made to stabilize the mother's condition under therapeutic volume expansion. Pregnancy was terminated with the onset of a renewed HELLP episode. - RESULTS: HELLP syndrome occurred with an incidence of 1 : 310 births. There were no maternal or neonatal deaths or any severe complications. Prolonging pregnancy until completing drug-induced lung maturity was successful in 16 of 25 patients before the 34(th) week of pregnancy. In the case of immediate delivery with inadequate stabilization, 5 of 9 patients had postpartum complications. A severe RDS occurred in 3 premature babies without drug-induced maturity. - CONCLUSION: If there is no life-threatening risk to the fetus or mother in patients with HELLP syndrome, the objective is the prolongation of pregnancy in a perinatal center until lung maturation. Stabilization is successful in a high percentage of patients under therapeutic volume expansion with optimal monitoring of mother and child.

Adult↗
PubMed2001

Identification of the prostate cancer micro-foci with chromosome 8p deletion at the tumor interface area by histopathological-FISH parallel examination.

We used a histopathological-fluorescence in situ hybridization (histo-FISH) parallel examination technique to identify the micro-foci of prostate cancer with chromosome 8p deletion at the interface area adjacent to the tumor. The archival paraffin embedded prostate tissue sections from 27 prostate cancer patients were evaluated. Seventy-eight percent of the patients showed chromosome 8p deletion in the tumor sections. Eight of the 27 patients (30%) had been found positive for tumor micro-foci with chromosome 8p deletion at the tumor interface area. There is a strong trend for patients with late stage tumors to have positive findings for tumor micro-foci at the interface area (p<0.002). Our data suggests that the formation of tumor micro-foci with chromosome 8p deletion and ploidy change at the interface area is a significant development in the advanced prostate cancer, and identification of these micro-foci may serve as a prognostic parameter in the clinical assessment of prostate cancer patients.

Aged↗
PubMed2001

A rational approach to the selection and sequencing of nucleoside/nucleotide analogues: a new paradigm.

While the value of highly active antiretroviral therapy (HAART) is unquestionable, its use as a life-long therapy will require a more structured and strategic approach to the sequential use of antiretroviral agents than has previously been the case. A complex cocktail of factors influences the durability of a given regimen, but the durability of HAART requires a carefully planned approach to the selection of agents across multiple regimens from first-line onwards, based on considerations of drug cross-resistance and sequenceability at regimen failure. Despite considerable ongoing interest in sequencing protease inhibitors and even non-nucleoside reverse transcriptase inhibitors, there has been little study into the optimal sequence of nucleoside reverse transcriptase inhibitor (NRTI) drugs in consecutive regimens. Historical practice, clinical experience and force of habit have all emphasized the use of thymidine analogue-based first-line combinations and the frequent retention of a thymdine analogue at all subsequent stages until a salvage situation is reached. Emerging data clearly associates thymidine analogue-derived reverse transcriptase mutations with loss of drug susceptibility and clinical response to other members of the NRTI class, particularly when present alongside other NRTI-associated mutations. Any approach to strategic therapy across multiple treatment lines will require, as a basic tenet, that agents with the greatest potential for cross-resistance be used later in therapy rather than earlier. To this end, a move away from the universal use of the thymidine analogues in first-line therapy is likely as strategic thinking becomes more integrated into clinical management in HIV disease. However, more clinical investigation is required into both the performance of alternative first-line

Anti-HIV Agents↗
PubMed2000

Copper(II) and copper(I) complexes with an open-chain N4 Schiff base ligand modeling CuZn superoxide dismutase: structural and spectroscopic characterization and kinetics of electron transfer.

The structure of the complex [CuII(PuPy)](ClO4)2 (PuPy = L = 1,8-bis(2-pyridyl)-2,7-diazaoctadiene-1,7) and the structure of the corresponding copper(I) complex were determined. In CuIIL(ClO4)2, a model compound with CuZnSOD activity, the unit CuIIL2+ has a tetrahedrally distorted square-planar N4 coordination geometry. The copper(I) complex with L was found to be dimeric, (CuIL)2(ClO4)2.DMF (DMF = N,N-dimethylformamide). The binuclear unit (CuIL)2(2+) has a helical structure with two ligands L bridging the two copper atoms to provide tetrahedral N4 coordination of each copper(I). In solutions of (CuIL)2(ClO4)2.DMF, solvent-dependent dissociation occurs according to D reversible 2M (D = (CuIL)2(2+); M = CuILSx+; S = solvent). Stopped-flow spectrophotometry was used to determine the rate constants for the dissociation of the dimer D (kM) and dimerization of the monomer M (kD) for S = acetonitrile and DMF. Equilibrium constants Kdim = kM/kD were determined spectrophotometrically. In aqueous solution, the oxidation of the dimer (CuIL)2(2+) by CoIII(NH3)5Cl2+ and cis- and trans-CoIII(en)2Cl2+ follows a second-order rate law, rate = kox[(CuIL)2(2+)][Co(III)]. Data for rate constant kox and for the activation parameters delta H++ and delta S++ are presented. In DMF, the oxidation of (CuIL)2(2+) by CoIII(NH3)5Cl2+ occurs via the monomer CuIL(DMF)x+ and the dissociation of (CuIL)2(2+) becomes rate-controlling. The reduction of CuIIL2+ by RuII(edta)H2O2- was found to be too fast to be resolved by stopped-flow spectrophotometry. The kinetic results are discussed mechanistically in terms of the redox switch aspects of the system.

Copper↗
PubMed2000

Vascular endothelial growth factor-A-induced chemotaxis of monocytes is attenuated in patients with diabetes mellitus: A potential predictor for the individual capacity to develop collaterals.

BACKGROUND: Vascular endothelial growth factor-A (VEGF-A) acts on endothelial cells and monocytes, 2 cell types that participate in the angiogenic and arteriogenic process in vivo. Thus far, it has not been possible to identify differences in individual responses to VEGF-A stimulation because of the lack of an ex vivo assay. METHODS AND RESULTS: We report a chemotaxis assay using isolated monocytes from individual diabetic patients and from healthy, age-matched volunteers. The chemotactic response of individual monocyte preparations to VEGF-A, as mediated via Flt-1, was quantitatively assessed using a modified Boyden chamber. Although the migration of monocytes from healthy volunteers could be stimulated with VEGF-A (1 ng/mL) to a median of 148.4% of the control value (25th and 75th percentiles, 136% and 170%), monocytes from diabetic patients could not be stimulated with VEGF-A (median, 91.1% of unstimulated controls; 25th and 75th percentiles, 83% and 98%; P<0.0001). In contrast, the response of monocytes to the chemoattractant formylMetLeuPhe remained intact in diabetic patients. The VEGF-A-inducible kinase activity of Flt-1, as assessed by in vitro kinase assays, remained intact in monocytes from diabetic patients. Moreover, the serum level of VEGF-A, as assessed by immunoradiometric assay, was significantly elevated in diabetic patients. CONCLUSIONS: The cellular response of monocytes to VEGF-A is attenuated in diabetic patients because of a downstream signal transduction defect. These data suggest that monocytes are important in arteriogenesis and that their ability to migrate might be critical to the arteriogenic response. Thus, we resolved a fundamental mechanism involved in the problem of impaired collateral formation in diabetic patients.

Aged↗
PubMed2000

An algorithm for clustering cDNA fingerprints.

Clustering large data sets is a central challenge in gene expression analysis. The hybridization of synthetic oligonucleotides to arrayed cDNAs yields a fingerprint for each cDNA clone. Cluster analysis of these fingerprints can identify clones corresponding to the same gene. We have developed a novel algorithm for cluster analysis that is based on graph theoretic techniques. Unlike other methods, it does not assume that the clusters are hierarchically structured and does not require prior knowledge on the number of clusters. In tests with simulated libraries the algorithm outperformed the Greedy method and demonstrated high speed and robustness to high error rate. Good solution quality was also obtained in a blind test on real cDNA fingerprints.

Algorithms↗
PubMed2000

Safety and efficacy of dynamic graciloplasty for fecal incontinence: report of a prospective, multicenter trial. Dynamic Graciloplasty Therapy Study Group.

PURPOSE: Dynamic graciloplasty has been used for intractable fecal incontinence, and good results have been reported. The aim of this study was to assess prospectively the safety and efficacy of dynamic graciloplasty for intractable fecal incontinence in a prospective, multicenter trial. METHODS: A total of 123 adults were treated with dynamic graciloplasty at 20 institutions. Continence was assessed preoperatively and postoperatively by use of 14-day diaries. RESULTS: There was one treatment-related death. One hundred eighty-nine adverse events occurred in 91 patients (74 percent). Forty-nine patients (40 percent) required one or more operations to treat complications. One hundred seventy (90 percent) events were resolved. Sixty-three percent of patients without pre-existing stomas recorded a 50 percent or greater decrease in incontinent events 12 months after dynamic graciloplasty, and an additional 11 percent experienced lesser degrees of improvement. Twenty-six percent were not improved, worsened, or exited. In patients with pre-existing stomas, 33 percent achieved successful outcomes at 12 months. This number increased to 60 percent at 18 months. Seventy-eight percent of patients had increased enema retention time, and mean anal canal pressures improved significantly at 12 months. Significant changes in quality of life were also observed. CONCLUSIONS: Objective improvement can be demonstrated in the majority of patients with end-stage fecal incontinence treated with dynamic graciloplasty. Reduction in incontinence episodes can be correlated with improved quality of life. Adverse events are frequently encountered, but most resolve with treatment.

Adolescent↗
PubMed2000

Idiopathic segmental infarction of the greater omentum successfully treated by laparoscopy: report of case.

Idiopathic or spontaneous segmental infarction of the greater omentum (ISIGO) is a rare cause of acute right-sided abdominal pain. The symptoms simulate acute appendicitis in 66% of cases and cholecystitis in 22%. Progressive peritonitis usually dictates laparotomy, and an accurate diagnosis is rarely made before surgery. The etiology of the hemorrhagic necrosis is unknown, but predisposing factors such as anatomic variations in the blood supply to the right free omental end, obesity, trauma, overeating, coughing, and a sudden change in position may play a role in the pathogenesis. We present herein the case of a 37-year-old man in whom ISIGO, precipitated by obesity and overeating, was successfully diagnosed and treated by laparoscopy. Resection of the necrotic part of the greater omentum is the therapy of choice, and ensures fast recovery and pain control. Serohemorrhagic ascites is a common finding in ISIGO, and careful exploration of the whole abdominal cavity should be performed. The laparoscopic approach allows both exploration and surgical intervention.

Abdomen, Acute↗
PubMed2000

Differential expression of eight chitinase genes in Medicago truncatula roots during mycorrhiza formation, nodulation, and pathogen infection.

Expression of eight different chitinase genes, representing members of five chitinase classes, was studied in Medicago truncatula roots during formation of arbuscular mycorrhiza with Glomus intraradices, nodulation with Rhizobium meliloti, and pathogen attack by Phytophthora megasperma f. sp. medicaginis, Fusarium solani f. sp. phaseoli (compatible interactions with root rot symptoms), Ascochyta pisi (compatible, symptomless), and F. solani f. sp. pisi (incompatible, nonhost interaction). In the compatible plant-pathogen interactions, expression of class I, II, and IV chitinase genes was enhanced. The same genes were induced during nodulation. Transcripts of class I and II chitinase genes accumulated transiently during early stages of the interaction, and transcripts of the class IV chitinase gene accumulated in mature nodules. The pattern of chitinase gene expression in mycorrhizal roots was markedly different: Expression of class I, II, and IV chitinase genes was not enhanced, whereas expression of three class III chitinase genes, with almost no basal expression, was strongly induced. Two of these three (Mtchitinase III-2 and Mtchitinase III-3) were not induced at all in interactions with pathogens and rhizobia. Thus, the expression of two mycorrhiza-specific class III chitinase genes can be considered a hallmark for the establishment of arbuscular mycorrhiza in Medicago truncatula.

Amino Acid Sequence↗