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Biomedical subjects

L Lange

Publications and source records attributed to L Lange.

At least 19 recordsLinked to original sources
PubMed2001

Antioxidant inhibition of porphyrin-induced cellular phototoxicity.

Porphyrins such as protoporphyrin IX (PP IX) and uroporphyrin I (UP I) can be phototoxic to human cells. To study the protective ability of antioxidants (beta-carotene, lycopene, ascorbic acid and alpha-tocopherol), against such porphyrin phototoxicity, membrane destruction experiments (Jurkat cells) and human cell cultures (fibroblasts) were performed. Both beta-carotene and lycopene and also the combination of beta-carotene, ascorbic acid and alpha-tocopherol offered cell protection against PP IX phototoxicity. Investigations of both cell membrane protection and of cell growth showed differences in terms of the protection afforded by the anti-oxidants. Thus, for PP IX, carotenoids alone, and in combination with ascorbic acid and alpha-tocopherol, showed higher protection factors in general than UP I. However, for membrane protection there was significant protection against UP I by the combination of beta-carotene, ascorbic acid and alpha-tocopherol but not by any of these anti-oxidants alone. The membrane protection against PP IX by beta-carotene, and especially lycopene, is significant presumably because of the high lipophilicity of all these molecules. However, the hydrophilic UP I will cause phototoxicity mainly via H(2)O(2), radical or singlet oxygen production in the aqueous phase, and these reactive species may be generated some distance from the cell membrane. This may lead to the little or no protection observed for UP I by the individual antioxidants. Nevertheless, a combination of beta-carotene, ascorbic acid and alpha-tocopherol offers membrane protection against the phototoxicity of both porphyrins. This is believed to occur as a result of synergistic processes. Our results suggest that the treatment of porphyria cutanea tarda and erythropoietic protoporphyria may be improved by the use of a combination of the antioxidants studied.

Antioxidants↗
PubMed2001

Provider encouragement of breast-feeding: evidence from a national survey.

OBJECTIVE: To examine the influence of provider encouragement on breast-feeding among women of different social and ethnic backgrounds in the United States. METHODS: A nationally representative sample of 2017 parents with children younger than 3 years was surveyed by telephone. The responses of the 1229 women interviewed were included in the analysis. Respondents were asked to recall whether their physicians or nurses had encouraged or discouraged them from breast-feeding. The effects of provider encouragement on breast-feeding initiation and duration were evaluated by multivariate logistic regression. The sample was then stratified to allow subset analyses by race and ethnicity, education, income class, age group, and marital status. RESULTS: More than one-third (34.4%) of respondents did not initiate breast-feeding. Three-fourths (73.2%) of women reported having been encouraged by their physicians or nurses to breast-feed; 74.6% of women who were encouraged initiated breast-feeding, compared with only 43.2% of those who were not encouraged (P < 0.001). Women who were encouraged to breast-feed were more than four times (relative risk 4.39; 95% confidence interval 2.96, 6.49) as likely to initiate breast-feeding as women who did not receive encouragement. The influence of provider encouragement was significant across all strata of the sample. In populations traditionally less likely to breast-feed, provider encouragement significantly increased breast-feeding initiation, by more than threefold among low-income, young, and less-educated women; by nearly fivefold among black women; and by nearly 11-fold among single women. CONCLUSION: Provider encouragement significantly increases breast-feeding initiation among American women of all social and ethnic backgrounds.

Adult↗
PubMed2001

Fibroblasts require protein kinase C activation to respond to hyaluronan with increased locomotion.

Hyaluronan (HA) stimulates the motility of some but not all cell types. Here, we show that HA-promoted random motility of ras-transformed 10T1/2 (C3) fibroblasts requires activation of protein kinase C and is associated with rapid uptake of HA in a CD44 and RHAMM-dependent manner. The addition of HA to parental 10T1/2 fibroblasts (parental cells) does not stimulate random motility, but these cells can be 'primed' to respond to HA by treatment with the phorbol ester, PMA, for 4-6 h. This effect of PMA requires protein synthesis, PKC activity and is associated with enhanced uptake of HA. These results suggest that the ability of cells to respond to HA is regulated by a protein kinase C-dependent process that may promote uptake of HA.

Cell Line↗
PubMed2001

Short-term and long-term outcomes after bilateral lung volume reduction surgery : prediction by quantitative CT.

OBJECTIVES: To evaluate selection criteria and duration of benefit for patients undergoing lung volume reduction surgery (LVRS). METHODS: Eighty-nine consecutive patients with severe emphysema who underwent bilateral LVRS were prospectively followed up for up to 3 years. Patients underwent preoperative pulmonary function testing, 6-min walk, chest CT, and answered a baseline dyspnea questionnaire. CT scans in 65 patients were analyzed for emphysema extent and distribution using the percentage of emphysema in the lung, percentage of normal lower lung, and the CT emphysema ratio (CTR, an index of the craniocaudal distribution of emphysema). All patients underwent at least 6 weeks of pulmonary rehabilitation prior to surgery. Outcome measures were FEV(1), 6-min walk distance, and transitional dyspnea index (TDI). RESULTS: Compared to baseline, FEV(1) was significantly increased at 3, 6, 12, 18, 24, and 36 months after surgery (p < or = 0.008). The 6-min walk distance increased from 871 feet (baseline) to 1,110 feet (3 months), 1,214 feet (6 months), 1,326 feet (12 months), 1,342 feet (18 months), 1,371 feet (24 months), and 1,390 feet (36 months) after surgery. Despite a decline in FEV(1) over time, 6-min walk distance was preserved. Dyspnea as measured by TDI improved at 3, 6, 12, 18, 24, and 36 months after surgery. A high CTR was the best predictor of a 12% increase over baseline and an absolute increase of 200 mL in FEV(1), although with a low area under the receiver operating characteristic curve. In addition, the sensitivity and negative predictive value of the CTR were limited. No radiographic or physiologic predictor was able to consistently predict a successful increase in walk distance or TDI. CONCLUSION: LVRS improves pulmonary function, decreases dyspnea, and enhances exercise capacity in many patients with severe emphysema, although improvement wanes 36 months after surgery.

Adult↗
PubMed1999

Physician perceptions of barriers to care for inner-city Latino children with asthma.

This article describes physician perspectives on barriers to quality primary care experienced by inner-city children with asthma and presents policy recommendations to reduce these barriers. The authors interviewed 30 physicians who take care of children with asthma in an inner-city Latino neighborhood, conducted a qualitative analysis of interview themes, and used a consensus group method to recommend policy actions. Inner-city physicians described significant access, quality of care, and other barriers in providing state-of-the-art primary care for asthma. Physicians recommended that eliminating financial barriers to care, including lack of health insurance and/or comprehensive health coverage for necessary medications and equipment, is the most important required policy action. In addition, inner-city physicians recommended that medical care and public health programs provide bilingual education for children with asthma and their families and train primary care physicians about how to provide effective asthma care to children with asthma in the inner city.

Adult↗
PubMed1998

Rapid hyaluronan uptake is associated with enhanced motility: implications for an intracellular mode of action.

Texas red-labeled hyaluronan (TR-HA) is rapidly taken up in a CD44 independent manner into ras-transformed 10T1/2 fibroblasts, where it accumulates in both cell ruffles/lamellae, the perinuclear area, and the nucleus. HA does not accumulate in the cell ruffles/lamellae of parental 10T1/2 cells. Addition of HA to ras-transformed cells promotes their random motility but has no effect on 10T1/2 cell motility. 10T1/2 cells can be modified to take up HA into cell ruffles by exposure to phorbol ester or direct microinjection of HA into cells. Both treatments significantly stimulate 10T1/2 cell motility.

Animals↗
PubMed1998

Enhanced protection of human cells against ultraviolet light by antioxidant combinations involving dietary carotenoids.

Antioxidants like beta-carotene, alpha-tocopherol and ascorbic acid should be able to protect human cells against damage due to ultraviolet light. Cultured human fibroblasts have been irradiated with UVA or UVB light after incubation with the antioxidants or combinations of them. The efficiency of the protection by the antioxidants in dietary concentrations is estimated by cell counting following cell culture. In the case of UVA irradiation we find synergistic effects of combinations with beta-carotene as the main protector. On the other hand, only additive effects of the tested combinations are observed in the experiments with UVB light. Our experiments show a protective effect of dietary antioxidants against human tissue cell damage by ultraviolet light.

Antioxidants↗
PubMed1998

Using molecular techniques to identify new microbial biocatalysts.

Evolution has favoured microorganisms that produce efficient enzymes with substrate-adapted biocatalytic activities. Progress in molecular techniques, especially expression cloning, molecular screening, protein engineering and in vivo and in vitro shuffling, have paved the way for greater speed and accuracy in cloning enzyme genes from microorganisms and generating versions with improved properties. Recently, two new approaches have been added: screening directly from uncultivated microorganisms and generating additional hits by database mining using bioinformatic tools.

Amino Acid Sequence↗
PubMed1996

[Adults with congenital heart defects--clinical spectrum and surgical management].

Two hundred adults who underwent surgery for congenital heart disease at our institution within a four year period were the basis for this report. Clinical data was obtained, i.e. demographic details, past medical history, physical findings, EKGs, echocardiograms, catheterization and angiography material as well as the New York Heart Association (NYHA) class. Intraoperative findings, perioperative management, complications and morbidity and mortality were assessed. After discharge the patients were followed on an outpatient basis. Again the clinical findings, laboratory results and NYHA class were recorded. Age ranged from 16 to 75 years (mean = 38). There were 114 females and 86 males. 178 patients had primary surgical correction, 18 were reoperated after prior correction and 4 underwent palliation. Eighty-three percent of the patients were symptomatic preoperatively. Seventeen percent were diagnosed per chance, for example by a preemployment physical examination, without a prior history of heart disease. The patients were grouped according to related diagnoses (Table 1). Among the 130 patients with left to right shunts, 112 had an atrial septal defect, 7 a ventricular septal defect, 5 a persistent ductus arteriosus, and 6 partial anomalous pulmonary venous return. Atrial flutter or fibrillation occurred in approximately 10% of all patients with atrial septal defects. It was terminated either by rapid overdrive pacing or DC cardioversion. Postoperatively the patients with pulmonary hypertension were monitored invasively with arterial lines and thermodilution catheters. Therapy consisted of alkalization, hyperventilation and sedation. There was only one postoperative death in this patient group due to marked pulmonary hypertension (1/130 = 0.8%). Nineteen adults had obstruction to right or left ventricular outflow. Surgery included valvotomy, infundibulectomy and valve replacement by homograft or mechanical valve. One patient with multiple previous surgeries expired due to bleeding (3%). Thirteen patients had coarctation. All of them were hypertensive, some on medication. Surgery consisted of aortic patchplasty or interposition of a graft. There was no mortality. Perioperative antihypertensive therapy was necessary in most patients and consisted of nifedipin, nitroprussid or propanolol intravenously. Upon follow up 11 patients became normotensive, 8 of these without the need for medication. Fifteen cyanotic patients underwent 11 corrective and 4 shunt procedures (3 with tricuspid atresia, 10 with Tetralogy of Fallot and 2 with complex cyanotic heart disease. Three died due to low cardiac output or dysrhythmias (20%). The survivors improved their clinical status markedly. Seven adults with Ebstein's disease had valve reconstruction and/or ASD closure. Five had recurrent supraventricular tachycardia, 2 paradoxical emboli with neurological symptoms and 4 out of 7 had decreased exercise tolerance. One patient died postoperatively because of dysrhythmias (14%). Sixteen patients had a variety of defects, i.e. status post Rastelli operation and conduit obstruction, status post Tetralogy of Fallot with pulmonary valvar disease, corrected transposition with left AV valve insufficiency, congenital mitral valve disease and double aortic arch, no deaths. The overall operative mortality was 6/200 = 3%. the late mortality was 4/200 = 2%. The morbidity included 7 reoperations due to bleeding. Five patients needed short-term hemodialysis. One patient developed hemiplegia and two patients had permanent decrease of their left ventricular function. The mean length of follow up was 21 months. The clinical status improved from a NYHA class mean of 2.1 +/- 0.9 to 1.2 +/- 0.45 (p < 0.001). In Germany significant numbers of adults with operated and unoperated congenital heart disease do exist. Detection of these patients can be difficult due to inconspicuous murmurs or stable clinical status.

Adolescent↗
PubMed1995

Phase I clinical evaluation of Gd-EOB-DTPA as a hepatobiliary MR contrast agent: safety, pharmacokinetics, and MR imaging.

PURPOSE: To determine the safety, pharmacokinetics, and magnetic resonance (MR) imaging results of gadolinium ethoxybenzyl diethylenetriaminepentaacetic acid (Gd-EOB-DTPA) as a contrast agent for use in hepatobiliary MR imaging. MATERIALS AND METHODS: Gd-EOB-DTPA was tested at doses of 10, 25, 50, and 100 mumol per kilogram of body weight. Results of laboratory tests, clinical measurements, and pharmacokinetic data were obtained in 44 healthy volunteers in a double-blind, randomized, placebo-controlled design. MR images were obtained in another 16 healthy volunteers before and up to 6 hours after fast intravenous administration of Gd-EOB-DTPA. RESULTS: Gd-EOB-DTPA was well tolerated, with no important side effects or changes in laboratory parameters. Homogeneous enhancement of liver parenchyma was observed immediately after injection of the contrast agent. Peak liver signal intensity was noted 20 minutes after injection, followed by plateaulike enhancement over about 2 hours. The common bile duct was hyperintense within 10 minutes after injection in all volunteers. CONCLUSION: Gd-EOB-DTPA is safe and efficient for MR imaging of the liver.

Adult↗
PubMed1995

Validation of an in vivo wound healing model for the quantification of pharmacological effects on epidermal regeneration.

BACKGROUND: Non-invasive assessment methods such as measurement of the transepidermal water loss (TEWL) allow a continuous follow-up of cutaneous processes with impairment of the epidermal barrier function. OBJECTIVE: The aim of the trial was to establish an in vivo model for the assessment of drug effects on epidermal regeneration. METHODS: Twenty healthy volunteers were included in this double-blind randomized trial. After setting four suction blisters on the volar aspect of the forearm, the epidermis was removed to create a standardized subepidermal wound. Thereafter the wounds were treated topically for 6 h daily during 14 days. The following treatments were to be compared: a clobetasol 17-propionate preparation under occlusion, a corticoid-free cream under occlusion, no treatment and occlusion (aluminium chamber), no treatment and no occlusion. Daily measurement of TEWL above the wounds was performed. RESULTS: The 0.05% clobetasol 17-propionate preparation caused a dramatic delay in TEWL decrease, whereby the untreated unoccluded field showed a continuous decrease over the observed period of 14 days. Occlusion and corticoid-free treatment led to a weak but significant delay of TEWL decrease when compared to the untreated unoccluded test field. CONCLUSION: This model seems to describe re-epithelialization in a reliable manner and can be used for in vivo assessment of drug effects on migrating and proliferating epithelial cells.

Adult↗
PubMed1994

Pharmacokinetics, dose proportionality, and tolerability of gadobutrol after single intravenous injection in healthy volunteers.

RATIONALE AND OBJECTIVES: Gadobutrol is a new gadolinium-based hydrophilic and neutral macrocyclic contrast medium for magnetic resonance imaging. In this article, the authors report on the first application of gadobutrol in humans, up to a dose of 0.5 mmol/kg. METHODS: Gadobutrol was investigated after single intravenous administration in two phase-1 studies testing low (0.5 mol/L) and high concentrations (1 mol/L) in healthy, male volunteers using a double-blind, randomized, placebo-controlled study with n = 55 for the low concentration (0.04, 0.1, 0.2, 0.3, and 0.4 mmol/kg body weight), followed by n = 36 for the high concentration (0.3, 0.4, and 0.5 mmol/kg body weight). Vital signs and laboratory parameters were measured for all dose groups investigated, whereas for the calculation of the pharmacokinetic parameters, the dose groups 0.04, 0.1, and 0.4 mmol/kg body weight were selected. RESULTS: Gadobutrol was well tolerated up to doses of 0.5 mmol/kg, and no relevant changes in vital signs and laboratory parameters occurred. The terminal disposition half-life of gadobutrol in plasma was approximately 1.5 hours. Total clearance approximated renal clearance and approximated the value of 120 mL/min, indicating glomerular filtration as the main pathway of elimination. The steady-state volume of distribution indicated predominantly extracellular distribution of gadobutrol. No metabolites were detected. The renal excretion rate was linear over the large dose range tested, indicating dose-proportionate, first-order kinetics of gadobutrol. CONCLUSION: Single intravenous administration of gadobutrol was well tolerated up to the dose level of 0.5 mmol/kg body weight. These factors suggest that gadobutrol will be a safe magnetic resonance imaging contrast agent.

Adult↗
PubMed1993

Comparison of the local and systemic side effects of methylprednisolone aceponate and mometasone furoate applied as ointments with equal antiinflammatory activity.

BACKGROUND: The therapy for skin diseases with topical glucocorticoids is limited by their local and systemic side effects. A glucocorticoid with an improved benefit-to-risk ratio is desirable. OBJECTIVE: A new topical corticoid, methylprednisolone aceponate (MPA) 0.1% ointment, was compared with the same formulation of mometasone furoate. METHODS: The two ointments were compared with respect to suppression of UVB light-induced erythema (n = 20) and with respect to atrophogenicity and appearance of telangiectasia (n = 20) in two double-blind trials with intraindividual comparisons in healthy volunteers. In a third trial, serum cortisol levels were measured in volunteers receiving extensive (60% of body surface) cutaneous application of MPA (n = 10) or mometasone furoate (n = 11). RESULTS: MPA and mometasone furoate were equally effective in suppressing UVB light-induced erythema. Atrophogenicity, as well as the incidence and severity of telangiectasia, were significantly more pronounced with mometasone furoate than with MPA. Both ointments decreased serum cortisol levels and did not differ significantly in this respect. However, the incidence of serum cortisol level suppression was higher in the mometasone furoate group than in the MPA group. CONCLUSION: MPA ointment has equal antiinflammatory activity and similar cortisol suppression but significantly fewer local side effects than mometasone furoate.

Administration, Topical↗