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Biomedical subjects

S Lange

Publications and source records attributed to S Lange.

At least 109 records · Page 6Linked to original sources

Long-term follow-up of HBeAg-positive patients treated with interferon alfa for chronic hepatitis B.

BACKGROUND: In patients with chronic hepatitis B, treatment with interferon alfa and the consequent loss of hepatitis B e antigen (HBeAg) from the blood leads to a reduction in inflammatory activity, but the clinical benefits of this treatment have not been established. We evaluated whether HBeAg seroconversion induced by interferon alfa improves clinical outcome. METHODS: We studied prospectively a cohort of 103 patients treated with interferon alfa for chronic hepatitis B; the mean (+/- SD) follow-up was 50.0 +/- 19.8 months. Fifty-three untreated patients served as controls. RESULTS: After treatment with interferon alfa, 53 of 103 patients no longer had detectable HBeAg or hepatitis B virus DNA, although only 10 patients became seronegative for hepatitis B surface antigen (HBsAg) (Kaplan-Meier estimates of cumulative clearance rates at five years, 56.0 percent for HBeAg and 11.6 percent for HBsAg). Of the 53 untreated patients, only 7 spontaneously eliminated HBeAg (28.1 percent at five years), and all remained positive for HBsAg (p < 0.001 for the Comparison with the treated patients, by the proportional-hazards model). During follow-up, 6 of the 103 treated patients died of liver failure, and 2 needed liver transplantation, all 8 were persistently positive for HBeAg. In another eight treated patients, complications of cirrhosis developed; all but one of these patients remained positive for HBeAg. Overall survival and survival without clinical complications were significantly longer in patients who were seronegative for HBeAg after therapy with interferon alfa than in those who remained seropositive (P = 0.004 and P = 0.018, respectively). In a regression analysis, clearance of HBeAg was the strongest predictor of survival. Of the 53 untreated patients, 13 had severe complications (including 4 deaths and 1 need for liver transplantation); all 13 continued to be HBeAg-positive. CONCLUSIONS: In patients with chronic hepatitis B infection, the clearance of HBeAg after treatment with interferon alfa is associated with improved clinical outcomes.

Antiviral Agents↗

Comparison of leg compression stocking and oral horse-chestnut seed extract therapy in patients with chronic venous insufficiency.

BACKGROUND: Diseases of the venous system are widespread disorders sometimes associated with modern civilisation and are among the major concerns of social and occupational medicine. This study was carried out to compare the efficacy (oedema reduction) and safety of compression stockings class II and dried horse chestnut seed extract (HCSE, 50 mg aescin, twice daily). METHODS: Equivalence of both therapies was examined in a novel hierarchical statistical design in 240 patients with chronic venous insufficiency. Patients were treated over a period of 12 weeks in a randomised, partially blinded, placebo-controlled, parallel study design. FINDINGS: Lower leg volume of the more severely affected limb decreased on average by 43.8 mL (n = 95) with HCSE and 46.7 mL (n = 99) with compression therapy, while it increased by 9.8 mL with placebo (n = 46) after 12 weeks therapy for the intention-to-treat group (95% CI: HCSE: 21.1-66.4; compression: 30.4-63.0; placebo: 40.0-20.4). Significant oedema reductions were achieved by HCSE (p = 0.005) and compression (p = 0.002) compared to placebo, and the two therapies were shown to be equivalent (p = 0.001); in this design, however, compression could not be proven as standard with regard to oedema reduction in the statistical test procedure. Both HCSE and compression therapy were well tolerated and no serious treatment-related events were reported. INTERPRETATION: These results indicate that compression stocking therapy and HCSE therapy are alternative therapies for the effective treatment of patients with oedema resulting from chronic venous insufficiency.

Bandages↗

The role of the Lps gene in experimental ulcerative colitis in mice.

The effects of the Lps gene on the development of experimental ulcerative colitis were studied in two genetically different mouse strains: C57B1 and C3H. Acute colitis was induced by adding 3% dextran sulfate sodium (DSS) to the drinking water for a 7-day (C57B1 and C3H) or a 10-day (C57B1) experimental period. Although the DSS treatment initiated the same type of morphological changes in the colon in all groups of mice, an earlier onset and persistent intestinal bleeding occurred in the Lpsn mice (sensitive to lipopolysaccharide, LPS) in comparison with the Lpsd mice (hyporesponsive to LPS). Rectal bleeding appeared on day 7 in 90% of the Lpsn compared to 13% of the Lpsd mice (p < 0.0001). In C57B1 mice, followed for three additional days, 50% of the Lpsn mice died and the surviving animals showed as well as rectal bleeding a large number of Gram-negative bacteria in the liver and spleen. In contrast, the Lpsd mice of the C57B1 strain appeared unaffected by the treatment, although a transient rectal bleeding occurred in 90% on day 8. Also, significantly fewer Gram-negative bacteria were found in the liver and spleen. Even though significantly increased serum endotoxin levels were seen in all DSS-treated groups compared to controls on day 7, the serum levels of TNF alpha were significantly increased only in the Lpsn mice. In DSS-induced colitis the Lpsn genotype conferred on the mice an increased LPS susceptibility, resulting in an augmentation of the inflammatory response to Gram-negative bacteria and their endotoxins. The results suggest that LPS-induced host effector mechanisms significantly enhanced the intestinal bleeding, systemic inflammatory response, and mortality in mice with DSS-induced colitis. In addition, the host defense against the invading and systemically spread bacteria most probably involved additional genes.

Animals↗

[Prevention of osteoporosis: estrogen substitution paradigm].

There is an increasing belief among most physicians that hormone replacement therapy (HRT) is unquestionable efficacious to prevent osteoporotic fractures in women after the menopause. However, an analysis of the studies which are regarded as efficacy proof of HRT concerning the prevention of hip fractures--as the most important manifestation of osteoporosis--shows that the data are weaker than generally assumed: there are no randomised trials with regard to hip fracture prevention by HRT and the protective effect which is seen in the observational studies is inversely related to the methodical state of the respective type of study. Consequently, a bias cannot be excluded, while the so-called 'selection-by-health'-bias could play an outstanding role. For the efficacy proof of a treatment randomised controlled trials cannot be replaced by results of observational studies, however impressive they may be.

Bias↗

[Clinical relevance of incidental prostate carcinoma. A retrospective study].

Between July 1973 and December 1992, 5156 men underwent either TURP (n = 4259) or open prostatectomy (n = 897) because of infravesical obstruction supposedly due to benign prostatic hyperplasia (BPH). In this retrospective study, 86 men in whom an incidental carcinoma of the prostate had been found were followed up. Thirty-seven cases had been classified as pT1a tumor and 49 cases as pT1b tumor; 73 patients had undergone TURP and 13 open surgery. The mean age of the patients was 70.6 years (range 54-89). Twenty-seven patients (73%) with a pT1a tumor and 19 patients (38.8%) with a pT1b carcinoma received no further treatment. Radical prostatectomy was performed in four cases, one of pT1a and three of pT1b tumor. In all other cases the patients received androgen deprivation, and in four cases external radiotherapy was applied. With a mean follow-up of 5 years (range 17-229 months) 48 patients died (55.8%). The median survival was 73 months (95% CI: 52; 89). Compared to the overall population in the same age range, the standard mortality rate (SMR) was 1.72 and 2.05 (95% CI: 1.23; 2.21 and 1.46; 2.64 respectively) using the "Allgemeine Sterbetafel" of the Federal Republic of Germany (1949-1951 and 1986-1988). Using the log-rank test (P = 0.5, two-sided) no difference in survival was found between patients staged pT1a and pT1b. Ten of 48 patients dead at the time of evaluation died of prostate cancer. This means that 20.8% (pT1a n = 3; pT1b n = 7) of the patients succumbed to progressive disease during follow-up. All four patients who underwent radical prostatectomy are free of tumor at time of this evaluation. These results are in accordance with other studies. In younger men with incidental carcinoma of the prostate and life expectancy of more than 10 years, radical surgery of the prostate should be recommended.

Aged↗

[Immunologic effects of blood donation].

The effects of blood transfusion and blood donation on the immune system are still unclear. In a prospective study we investigated the effect of blood and blood component donation on several immunologic parameters. Lymphocyte subsets and cytokine levels were determined in 25 repeat whole-blood donors (RD), 25 plateletpheresis donors (PD), and 20 autologous blood donors (AD). First-time donors (FTD, n = 20) served as controls. Lymphocyte subsets and cytokines were determined using standard methods. Leukocytes, T-suppressor cells and natural killer (NK) cells were decreased in RD and PD when compared to FTD. Additionally, NK cells decreased with repeat donations in AD. No significant differences of cytokines in the different groups or during repeat autologous donations were observed.

Adult↗

[Electron beam tomography in coronary disease. Prevalence and distribution of coronary calcifications and their relationship with coronary risk factors in 650 patients].

OBJECTIVE: The extent of coronary calcification demonstrated by electron beam tomography was correlated with the individual cardiac risk profile. PATIENTS AND METHODS: The possible presence of coronary calcifications was studied by electron beam tomography (EBT) in 650 patients (526 men, 124 women; mean age 54 +/- 10 [28-81] years) with known or suspected coronary heart disease. Depending on the degree of density and the size of the lesion a score was calculated according to an international standard. RESULTS: No calcification was shown to be present in 202 patients (score of 0). A score of more than 0 was calculated in 73.8% of men and 48.4% of women. The average score was 227.8 +/- 24.8 in men, compared with 65.3 +/- 26.5 in women (P < 0.001). There were significantly more calcifications in older patients: Men aged 71-75 years had the highest score, 859.4, while the lowest, 9.6, was in those aged 36 to 40 years. The most important variables for the presence of calcification were age (relative risk per age group: 1.6), male sex (relative risk: 4.3), hypertension (relative risk: 2.4) and nicotine consumption (relative risk: 1.8). The median point score in patients without known risk factors was 1.3, with one known factor it was 7.2, and with three it was 48.0. The vessel segment most affected with calcification was the anterior interventricular branch with an average score of 84. CONCLUSION: Together with an evaluation of the risk profile EBT provided a better assessment of individual risk than conventional examination.

Adult↗

Molecular cloning and expression of a pituitary gland protein modulating intestinal fluid secretion.

Antisecretory factor (AF) is a protein known to inhibit intestinal fluid secretion induced by cholera toxin. cDNA clones, expressing immunoreactivity to AF were isolated from a human pituitary gland library and sequenced. The sequence contained 1309 base pairs plus a poly(A) tail; Northern blot analysis of pituitary RNA confirmed this size. One large open reading frame was found to code for 382 amino acids. The protein was expressed in pGEX-lambda 1T/Escherichia coli and purified. The recombinant AF was extremely potent, 9 ng (2.10(-13) mol), giving a significant antisecretory activity against cholera toxin-induced fluid secretion in rat. Antiserum against recombinant AF was used in immunohistochemical and Western blot analysis. Sections from human pituitary glands manifested specific intracellular staining in cells exclusively located in the anterior part. Both recombinant AF and AF extracted from pituitary gland appeared in SDS-polyacrylamide to have a molecular mass of 60 kDa, although the renal value was 41 kDa. The protein sequence manifested homology (29% identity) with one protein, a putative Saccharomyces cerevisiae 30-kDa protein of unknown function.

Amino Acid Sequence↗

Events per person year--a dubious concept.

In 1982 a new measure was introduced in research into osteoporosis and is now used everywhere in the literature. The so called "fracture rate" relates the number of fractures (single in some patients, multiple in others) to the cumulative time of observation of all patients. This concept, however, has no sound basis. Counting events instead of patients usually violates basic statistical assumptions and invalidates the use of common statistical tests and estimators. Its clinical interpretation is rather dubious. The use of such a measure impedes the search for valid and clinically meaningful outcome criteria and should be abandoned.

Estrogens↗

Adrenoceptor-mediated modulation of Evans blue dye permeation of rat small intestine.

In the present study, we addressed the problem whether sympathoadrenal mechanisms could influence the paracellular permeation of macromolecules from the lumen to the lamina propria of the small intestine. Experiments were conducted with rats that were anesthetized with ether for 10-20 min, during which time laparotomy was performed and six consecutive loops (each of 5 cm length) of the jejunum were prepared. A 3% solution of the azo dye, Evans blue (EB; MW 960.83) in phosphate-buffered saline, was instilled into each loop at a volume of 0.3 ml, this compound serving as a marker for tight junctional permeability. Thereafter, the abdomen was closed and the rats were allowed to wake up, but were killed after 60 min. The loops were dissected, opened, and rinsed with acetylcysteine in order to remove the adherent mucus layer. Each loop was weighed and incubated with formamide for 24 hr to elute the amount of EB absorbed, which was quantitated spectrophotometrically. In the control situation, the uptake was homogenous along the loops. beta-Adrenoceptor-blocking, or -stimulating agents could influence the uptake considerably. The data obtained could indicate that noradrenergic nerves, via an activation of beta 2-adrenoceptors, may cause an increase of tight junction permeability for macromolecules, but circulatory mechanisms also must be taken into account in order to explain the observed effects.

Animals↗

[Magnetocardiography for assessment of fetal heart actions].

Magnetocardiography provides a new, alternative method for fetal surveillance. This method allows the registration of changes in the magnetic field produced by the fetal cardiac system. In comparison to fetal ECG, the fetal magnetocardiogram (fMCG) is not affected by intermediate tissue, in particular by the insulating effect of the vernix caseosa. Furthermore fMCG's with a good signal noise ratio can be obtained in the second trimester. A multichannel biomagnetometer allows the non-invasive measurement of the magnetic signals produced by the fetus. Examples of dta and evaluation techniques are given. Signal processing software allows the identification of all fetal beats in a data set, permitting the calculation of an averaged beat and the evaluation of signal morphology and cardiac time intervals. Furthermore it is possible to produce a beat to beat time series with high temporal resolution, making the evaluation of heart rate variability with measures from the time, frequency, and phase domain accessible. Particularly the latter are of interest in investigating changes in temporal complexity of the fetal cardiac system. Magnetocardiography thus holds the promise of improved antenatal surveillance as of the second trimester.

Adult↗

[Microinvasive, CT-controlled periradicular therapy in treatment of chronic intervertebral disk-induced functional disorders].

The disease of the spinal column is number 2 of common diseases world-wide and leads to high business- and commerce-related losses as well as to high expenses for the health care systems. An effective treatment of this disease is given by the microinvasive. CT controlled periradicular therapy (micro PRT). Under visibility, the tip of a canula is led directly and high precisely in close neighbourhood to the prolaps, then locally NaCl and cristaline cortisone (40 mg Volon A) is instillated. The periradicular distribution and the distribution into the epidural space is documented via contrast medium. A retrospective study with 220 patients and a prospective randomized double blind study with 40 patients (10 mg vs. 40 mg Volon A) were carried out. The average age of the retrospective collective was 53.1 +/- 12.4 years, average treatment period 18.4 weeks, and the mean follow-up 17 months. The mean value of successful treatment of lumbal spine was at 60% (spine 88.5%) with protrusion, with prolaps at 75% (spine 94%), with sequester at 94%, and with stenoses at 69% (spine 60%). With 78.8% of the patients, the percentual result was constantly good at the time of questionnaire as to the end of the treatment. 7.7% still took analgesics, 5.9% were post-operated. 1.8% of the patients made a pension application. The average age of patients within the prospective randomized double-blind-study was 47.2 +/- 11.9 years. At 27.5% of the patients, the start of pain was about more than 5 years ago and goes back to about 23 years (72.5% had pain more than 1 year). The mean value of visits was 4 physicians per patient, and 5 months of follow-up. There is a high significant improvement in results within the group with 40 mg Volon A (p = 0.0351479). The entire improvement, subjectively estimated (visual analogical scale) within this group was at 90%. After end of therapy, 83.3% (n = 30) had stopped the taking of analgesics and the neurologic deficit decreased significantly. Furthermore, significant reduction of prolapses could be observed at 60% of the patients in both study groups (n = 156). The CT scopic micro PRT with 40 mg Volon A leads to a significant improvement of pain and neurologic symptoms caused by chronical disk herniation.

Adult↗

[Comparison of various methods of anesthesia by plasma catecholamine determination].

Three different methods of anaesthesia (propofol or isoflurane with fentanyl/alfentanil, atracurium and O2/air or neurolept-anaesthesia with fentanyl, dehydrobenzperidol, pancuronium and N2O/O2) were compared in 64 patients undergoing cardiac surgery before the start of extracorporeal circulation. Plasma catecholamine contents were determined and haemodynamic changes were recorded for the detection and quantification of sympathoadrenal responses to the typical points of stimulation (intubation, skin incision, sternotomy). The level of anaesthesia was held comparable by EEG monitoring (spectral edge frequencies between 8 and 12 Hz). Noradrenaline and adrenaline showed significantly lower values in the propofol group in comparison to the groups with isoflurane and neuroleptanaesthesia. The clearest increases in catecholamines were found in all groups before starting the extracorporeal circulation. There is no evident congruity between catecholamine levels and haemodynamic changes because of various interindividual differences. Derived values of haemodynamic parameters (integrals of blood pressure, rate pressure product and triple index) are more useful than single measurements for the description of circulatory reactions.

Anesthesia, General↗

[Effect of colloidal plasma substitutes on liberation of tumor necrosis factor-alpha (TNF-alpha) in human whole blood in vitro].

OBJECTIVE: To investigate the influence of colloidal plasma substitutes on human cytokine network, especially of tumor necrosis factor alpha (TNF-alpha), in vitro. DESIGN: Heparinized whole blood samples from 8 healthy volunteers were divided and set on various concentrations of artificial colloidal plasma substitutes (native = 0 mg/ml; 5 mg/ml; 15 mg/ml). As colloids were used hydroxyethyl starch 200/0.5 (HES), dextran 60 (DX), urea-linked gelatin (GEL) and human albumin solution (HA). After incubation (24 h; 5% CO2; 37 degrees C; with and without concomitant stimulation of blood cells with phytohemagglutinin [PHA]) measurement of TNF-alpha release was performed via ELISA by the method described by Gallati. For the statistical evaluation a repeated measures analysis of variance was used. RESULTS: Basic level of TNF-alpha was found between 226 and 273 pg/ml (0 mg of each colloid/ml), stimulation with PHA without any colloid increased the TNF-alpha level about fourfold (1,066-1,260 pg/ml; 0 mg of each colloid/ml). At 5 mg/ml and 15 mg/ml without PHA all 3 artificial colloids rose the level of TNF-alpha (up to 50%). Under concomitant stimulation each colloid induced additional TNF-alpha release in comparison to PHA alone. The changes elicited by DX and GEL were statistically significant (p < 0.001 and p = 0.005, respectively) in contrast to those induced by human albumin solution or HES. CONCLUSION: In relation to TNF-alpha plasma substitutes are not inert substances as perhaps suspected. The questions whether the observed effects exist in vivo how far other cytokines are influenced and the question about the clinical importance are subject of ongoing studies.

Colloids↗

Suppressed thyroid-stimulating hormone secretion in patients treated with interleukin-2 and interferon-alpha 2b for metastatic melanoma.

Recent reports suggest that combined therapy with recombinant interleukin (IL)-2 and interferon (IFN) alpha 2b may result in autoimmune-induced thyroid dysfunction. We prospectively analyzed thyroid function for 6 weeks in two groups of patients with progressive metastatic melanoma treated according to two different protocols. In group I (n = 17) three treatment cycles were given, each with three weeks of subcutanous administration of rIL-2 and INF-alpha 2b at different doses. In group II (n = 13) the chemotherapeutic agent dacarbazine was given in addition. In group 1 three patients developed frank hyperthyroidism, which required antithyroid drug therapy in one case. Autoantibodies against thyroid microsomal antigen, thyroglobulin, and the thyroid-stimulating hormone (TSH) receptor were not significantly elevated in any of these patients. However, the remaining 14 patients showed a significant decrease in TSH after 6 weeks of treatment, from 1.8 +/- 0.9 to 0.7 +/- 0.7 microU/ml (P < 0.02). Thyroid hormones (triiodothyronine, thyroxine, free thyroxine) also increased during the observation time, but this did not parallel the drop in TSH levels. Only thyroxine increased above the upper limit of normal, while triiodothyronine and free thyroxine stayed within the normal range. In group II, 6 of 13 patients (46%) had a decreased TSH after 6 weeks of treatment. Mean TSH was 1.5 +/- 1.4 before and 0.8 +/- 0.6 microU/ml after 6 weeks and was totally suppressed in three cases. None of these patients showed ouvert hyperthyroidism. Hypothyroidism was not observed in either group.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Effect of an anabolic steroid (Metenolon) on contractile performance of the chronically stimulated latissimus dorsi in sheep.

In 12 sheep the left latissimus dorsi muscles (LD) were conditioned by chronic electrostimulation with a pulse generator (Itrel, Medtronic). Six animals (group B) received a weekly intramuscular injection of an anabolic steroid (Metenolon). After 14 weeks the contraction parameters of the left LDs (group A and B) and right LDs (control group) were investigated. The increase in weight of the conditioned LDs was 11.07% (+/- 1.06%) in group A and 79.97% (+/- 40.8; P < 0.05) in group B. The force capacity under stimulation patterns which were just tetanic was 1.15 kp in group A and 4.13 kp in group B (P < 0.05); under supramaximal stimulation patterns it was 4.23 kp (A) and 6.0 kp (B) (P = ns). The force time relation (dF/dt) was 6.7 kp/s for the left LDs in group A versus 16.4 kp/s for the right LDs (P < 0.01); in group B it was 5.13 kp/s for the left LDs versus 15.8 kp/s for the control muscles (P < 0.05). The maximal force (Fmax) per 100 g muscle weight did not differ significantly (A: 2.42 kp/100 g; B: 2.52 kp/100 g). In conclusion, the LD muscles which were subjected to both anabolic therapy and electrical stimulation showed a significant increase in their force capacity due to an enormous increase in mass. Fibre type transformation was complete only in group B. No fibre deterioration was observable in either group. No anabolic side effects were detected in the animals. With the use of anabolic steroids, therefore, a clearer direct increase in contractility on the left ventricle should be expected ("squeezing" theory), as well as a contribution to reduction in wall tension and myocardial oxygen consumption, respectively, according to Laplace's Law (via the considerable increase in thickness).

Anabolic Agents↗

[Pelvimetry using various magnetic resonance tomography techniques vs. digital image enhancement radiography: accuracy, time requirement and energy exposure].

In 50 patients with suspected or proven cephalo-pelvine disproportion pelvimetry was performed with MR-tomography using a gradient-echo-sequence (FLASH 2D) before or after labour. Results were compared with measurements using digital radiography. In principle, both methods are exchangeable. The sagittal pelvic in- and outlet bispinous diameters are well reproducible. On the other hand, the transverse pelvic inlet and the distance between the ischiatic tubera are not so reliably reproduced. The accuracy of measurement does not depend on individual pelvic distances. Critical statistical analysis demonstrates, that in the worst case differences between the two methods might become unacceptable. Our results indicate two major reasons: 1. there are interobserver problems which cannot be neglected, and 2. the anatomical definition of referential landmarks for the measurements is unsafe. In 10 volunteers, a comparison was made between a T1-weighted spin-echo sequence (SE), a fast gradient echo sequence (FLASH-2D) and an ultrafast gradient echo technique (Turbo-FLASH). For the examination techniques presented here, the high-frequency exposure load or specific absorption rate (SAR loc and SAR total) is below the values permitted by the German Federal Health Bureau (Bundesgesundheitsamt). Whereas the exposure load in case of spin-echo takes (SE) is 22fold higher than with the gradient echo technique (GHE), the load values of ultra-fast GE (usGE) are only about 16% of the 2D-FLASH sequence or about 0.007% of SE. The difference in image quality does not affect the accuracy of measurement.

Adolescent↗