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1.
J Eur Acad Dermatol Venereol ; 36(10): 1774-1783, 2022 Oct.
Article in English | MEDLINE | ID: mdl-35460287

ABSTRACT

BACKGROUND: Limited data are available on long-term efficacy and safety of biologics in patients with psoriasis and metabolic syndrome (MetS), a common comorbidity. OBJECTIVES: This analysis updates tildrakizumab efficacy and safety for up to 5 years in patients with and without MetS. METHODS: This was a post hoc analysis of the double-blind, randomized, placebo-controlled, phase 3 reSURFACE 1 (NCT01722331) and reSURFACE 2 (NCT01729754) trials in adult patients with moderate to severe chronic plaque psoriasis. Analyses included data through Week 244 from patients who continuously received tildrakizumab 100 (TIL100) or 200 mg (TIL200) and entered the extension studies, stratified by baseline MetS status. Efficacy was assessed via Psoriasis Area and Severity Index (PASI) scores. Safety was evaluated from exposure-adjusted incidence rates (EAIRs) of treatment-emergent adverse events (TEAEs). RESULTS: reSURFACE 1 and reSURFACE 2 analyses included 26 and 44 TIL100-treated patients with MetS, 98 and 167 TIL100-treated patients without MetS, 34 and 30 TIL200-treated patients with MetS, and 111 and 130 TIL200-treated patients without MetS, respectively. There were no clinically relevant differences in PASI 75/90/100 response rates at Week 244 between patients with vs without MetS. The proportion of patients with vs without MetS achieving absolute PASI score <3 at Week 244 was 53.8% vs 69.4% and 77.3% vs 80.8% in reSURFACE 1 and 2, respectively, for TIL100-treated patients and 58.8% vs 72.1% and 63.3% vs 72.3%, respectively, for TIL200-treated patients. In both studies, median reduction from baseline PASI score at all time points in patients with vs without MetS was >83% vs >89% for TIL100 and >85% vs >90% for TIL200. Pooled EAIRs of TEAEs, serious TEAEs, and TEAEs of special interest were similar in patients with and without MetS. CONCLUSIONS: Tildrakizumab maintains efficacy and a favorable safety profile over 5 years in patients with psoriasis regardless of MetS status.


Subject(s)
Antibodies, Monoclonal, Humanized , Metabolic Syndrome , Psoriasis , Adult , Antibodies, Monoclonal, Humanized/adverse effects , Double-Blind Method , Humans , Metabolic Syndrome/complications , Metabolic Syndrome/drug therapy , Psoriasis/complications , Psoriasis/drug therapy , Treatment Outcome
2.
Int Angiol ; 34(3): 283-9, 2015 Jun.
Article in English | MEDLINE | ID: mdl-25027599

ABSTRACT

AIM: Recanalization of long segmental occlusions of femoropopliteal arteries can be achieved by angioplasty and implantation of nitinol stents with high procedural success rates. However, due to recurrent in-stent restenoses (ISR) some patients need repeated interventions and their intermediate success rates are uncertain. METHODS: Patients who were treated in our center from March 2008 through February 2011 due to symptomatic ISR (as determined by Duplex sonography) were retrospectively included in the study. After endovascular treatment of their ISR, they were prospectively evaluated with regard to recurrent ISR of the target lesions. RESULTS: A total of 36 limbs (=lesions) in 32 patients (69% male, mean age 69±9 years) were successfully treated by balloon-angioplasty. Adjunctive cutting balloons and drug eluting balloons were used in 78% and 8%, respectively. Mean follow-up was 326 days. Recurrent ISR occurred in 10 (28%) lesions, while 26 (78%) lesions showed no recurrence of ISR. In a multivariate logistic regression analysis, age, gender, cardiovascular risk factors, renal failure and medication with cilostazol were not significantly associated with recurrent ISR. Moreover, the number of previous interventions of the target lesions was not an independent predictor of recurrent ISR. CONCLUSION: Patients with multiple recurrences of ISR seem to have the same prospects of acute and mid-term success for endovascular treatment as those with first presentation of ISR. However, this observation has to be confirmed by prospective, large scale studies with a longer follow-up period to determine the significance of endovascular intervention within the scope of different revascularization approaches for treatment of recurrent ISR.


Subject(s)
Angioplasty, Balloon/adverse effects , Femoral Artery/pathology , Peripheral Arterial Disease/surgery , Popliteal Artery/pathology , Aged , Alloys , Constriction, Pathologic , Drug-Eluting Stents , Female , Femoral Artery/surgery , Humans , Logistic Models , Lower Extremity/blood supply , Male , Middle Aged , Multivariate Analysis , Popliteal Artery/surgery , Recurrence , Retrospective Studies , Risk Factors , Vascular Patency/drug effects
3.
Int Angiol ; 33(6): 518-29, 2014 Dec.
Article in English | MEDLINE | ID: mdl-24846745

ABSTRACT

AIM: Micro-lightguide spectrophotometry (O2C®) provides easily and rapidly measurable parameters of tissue microcirculation. The aim of this study was to assess whether micro-lightguide spectrophotometer (O2C®) based parameters of the tissue microcirculation can serve as predictors of ulcer healing. Furthermore, we tried to identify cut off values to forecast patient outcome and check other diagnostic meanings of individual O2C-parameters. METHODS: Forty individuals, all suffering from critical limb ischemia and arterial or arteriovenous ulcers were retrospectively investigated concerning O2C®- and ankle/toe brachial index-measurements before and up to two times after percutaneous transluminal angioplasty (PTA). At a median follow-up of 7 (range 3 to 14) months after PTA the current peripheral arterial disease (PAD) status, ulcer healing, adverse cardiovascular events including death and endovascular or surgical treatments were noted. RESULTS: We found in patients with healing wounds a significant increase in oxygen saturation (SO2, median 26.35±26.94%) compared to non-healers (-4.27±25.24%, P=0.006) as well as regarding blood flow (median 41.12±51.23AU vs. -9.46±24.01 AU, P=0.005). Additionally, the parameter rHb separated reliably between arterial and arteriovenous ulcers (P=0.024). In Cox regression models, increases after revascularisation of more than 6 % in SO2 (HRR=6.08, 95%CI 1.56-23.65, P=0.009) and flow decreases of less than 12 AU (HRR 4.95, 95%CI 1.42-17.31, P=0.012) were significantly associated with amputation-free survival. CONCLUSION: The O2C®-parameters SO2 and flow provide prognostic information for ulcer healing as well as for amputation-free survival, and rHB adds information about a possible arterial or arteriovenous genesis of an ulcer.


Subject(s)
Angioplasty , Ischemia , Leg Ulcer , Microspectrophotometry/methods , Oxygen Consumption , Peripheral Arterial Disease , Wound Healing , Aged , Aged, 80 and over , Angioplasty/adverse effects , Angioplasty/methods , Ankle Brachial Index/methods , Female , Humans , Ischemia/etiology , Ischemia/physiopathology , Leg Ulcer/etiology , Leg Ulcer/metabolism , Leg Ulcer/physiopathology , Lower Extremity/blood supply , Male , Microcirculation , Middle Aged , Peripheral Arterial Disease/complications , Peripheral Arterial Disease/diagnosis , Peripheral Arterial Disease/physiopathology , Peripheral Arterial Disease/surgery , Postoperative Care/methods , Predictive Value of Tests , Severity of Illness Index
4.
Br J Cancer ; 108(1): 131-8, 2013 Jan 15.
Article in English | MEDLINE | ID: mdl-23321515

ABSTRACT

BACKGROUND: Whether methylation of the microRNA (mir)-124-3 CpG island is of relevance for the clinical course of a solid cancer and whether it shows association with clinicopathology or survival of patients with renal cell cancer (RCC) is not known as yet. METHODS: In a cross-sectional study, relative methylation of mir-124-3 was measured in 111 RCC samples and 77 paired normal appearing tissues using quantitative methyl-specific PCR. Results were statistically compared with tumour histology, clinicopathological parameters and disease recurrence. RESULTS: We found tumour-specific hypermethylation of mir-124-3 in samples of RCCs with clear cell histology (ccRCC) compared with paired normal appearing tissues (P<0.0001). Methylation was significantly increased in tumours with state of advanced disease (P<0.0001). Higher relative methylation was associated with worse recurrence-free survival in both univariate (hazard ratio=9.37; P=0.0005) as well as bivariate Cox regression analyses considering age, sex, diameter of tumours and state of advanced disease, metastasis and lymph node metastases as covariates (hazard ratios=5.9-18.2; P-values of 0.0003-0.008). CONCLUSION: We identified mir-124-3 CpG islands (CGI) methylation as a relevant epigenetic mark for ccRCC thus underlining the need for functional studies of potentially affected signalling pathways in kidney tumour models. Methylation of mir-124-3 is suggested as an independent prognosticator for ccRCC.


Subject(s)
Carcinoma, Renal Cell/genetics , CpG Islands , DNA Methylation , Kidney Neoplasms/genetics , MicroRNAs/metabolism , Aged , Carcinoma, Renal Cell/pathology , Cell Line, Tumor , Disease-Free Survival , Female , Humans , Kidney Neoplasms/pathology , Male , Prognosis , Recurrence
5.
Rev Sci Instrum ; 80(7): 074501, 2009 Jul.
Article in English | MEDLINE | ID: mdl-19655969

ABSTRACT

We discuss the design, operation, and performance of a vacuum setup constructed for use in zero (or reduced) gravity conditions to initiate collisions of fragile millimeter-sized particles at low velocity and temperature. Such particles are typically found in many astronomical settings and in regions of planet formation. The instrument has participated in four parabolic flight campaigns to date, operating for a total of 2.4 h in reduced-gravity conditions and successfully recording over 300 separate collisions of loosely packed dust aggregates and ice samples. The imparted particle velocities achieved range from 0.03 to 0.28 m s(-1) and a high-speed, high-resolution camera captures the events at 107 frames/s from two viewing angles separated by either 48.8 degrees or 60.0 degrees. The particles can be stored inside the experiment vacuum chamber at temperatures of 80-300 K for several uninterrupted hours using a built-in thermal accumulation system. The copper structure allows cooling down to cryogenic temperatures before commencement of the experiments. Throughout the parabolic flight campaigns, add-ons and modifications have been made, illustrating the instrument flexibility in the study of small particle collisions.


Subject(s)
Cold Temperature , Particle Accelerators/instrumentation , Weightlessness , Computer-Aided Design , Copper , Dust , Equipment Design , Ice , Motion , Vacuum
6.
Br J Dermatol ; 161(4): 897-903, 2009 Oct.
Article in English | MEDLINE | ID: mdl-19545297

ABSTRACT

BACKGROUND: Clinical studies in cutaneous conditions other than actinic keratosis (AK) have revealed that the safety and efficacy profile of imiquimod is influenced by dosing frequency. OBJECTIVES: To evaluate dosing frequency response of imiquimod 5% for treatment of AK. METHODS: This was a phase II, multicentre, randomized, double-blind, placebo-controlled study. Adults with > or = 10 but < or = 50 clinical AKs, one of which was histologically confirmed, were randomized (4:1) to 2-6 packets of imiquimod or placebo cream applied to the dorsum of the forearms and hands once daily 2, 3, 5 or 7 times per week for 8 weeks. The primary endpoint was complete clearance of AKs in the treatment area at 8 weeks post-treatment. RESULTS: One hundred and forty-nine (94 men and 54 women) white subjects, with a mean +/- SD age of 71 +/- 10.2 years, were enrolled. Twenty-eight subjects (18.8%) discontinued from study: 0%, 3.1%, 6.9%, 30.0% and 33.3% withdrew for local skin reactions or adverse events in the combined placebo, and in the imiquimod 2, 3, 5 or 7 times per week groups, respectively. Seven serious adverse events occurred; none was related to the study drug. Median baseline lesions ranged from 38 to 40 for the treatment groups. Complete clearance was achieved in 0%, 3.2%, 6.9%, 3.3% and 6.7% of subjects, and partial clearance (> or = 75% lesion reduction) in 0%, 22.6%, 24.1%, 20.0% and 36.7% of subjects for the placebo and imiquimod 2, 3, 5 or 7 times per week regimens, respectively. CONCLUSIONS: Imiquimod 5% applied more frequently than 3 times per week to AKs was not well tolerated. Complete clearance rates were low; however, partial clearance rates increased with increased dosing frequency (P = 0.002).


Subject(s)
Adjuvants, Immunologic/administration & dosage , Aminoquinolines/administration & dosage , Hand Dermatoses/drug therapy , Keratosis, Actinic/drug therapy , Precancerous Conditions/drug therapy , Adjuvants, Immunologic/adverse effects , Administration, Cutaneous , Aged , Aminoquinolines/adverse effects , Dose-Response Relationship, Drug , Double-Blind Method , Drug Administration Schedule , Female , Forearm , Hand Dermatoses/pathology , Humans , Imiquimod , Keratosis, Actinic/pathology , Male , Precancerous Conditions/pathology , Treatment Outcome
7.
Arch Dis Child ; 91(11): 905-10, 2006 Nov.
Article in English | MEDLINE | ID: mdl-16798785

ABSTRACT

BACKGROUND: Concern exists that the prolonged application of immunomodulators to treat atopic dermatitis may cause systemic immunosuppression. AIMS: In a 7-month, multicentre, randomised, controlled trial, we investigated the equivalence of response to vaccination against meningococcal serogroup C disease with a protein-conjugate vaccine in children (2-11 years) with moderate to severe atopic dermatitis, by applying either 0.03% tacrolimus ointment (TAC-O; n = 121[corrected]) or a hydrocortisone ointment regimen (HC-O; n = 111). METHODS: TAC-O was applied twice daily (bid) for 3 weeks, and thereafter daily until clearance. 1% hydrocortisone acetate (HA) for head/neck and 0.1% hydrocortisone butyrate ointment for trunk/limbs was applied bid for 2 weeks; thereafter HA was applied bid to all affected areas. At week 1, patients were vaccinated with protein-conjugate vaccine against meningococcal serogroup C, and challenged at month 6 with low dose meningococcal polysaccharide vaccine. The control group (44 non-atopic dermatitis children) received the primary vaccination and challenge dose. Assessments were made at baseline, weeks 1 and 5, and months 6 and 7. The primary end point was the percentage of patients with a serum bactericidal antibody (SBA) titre > or = 8 at the week 5 visit. RESULTS: The response rate (patients with SBA titre > or = 8) was 97.5% (confidence interval (CI) approximately 97.3 to 100), 99.1% (94.8 to 100) and 97.7% (93.3 to 100) in the TAC-O, HC-O and control groups, respectively. CONCLUSIONS: The immune response to vaccination against meningococcal serogroup C in children with atopic dermatitis applying either 0.03% TAC-O or HC is equivalent. Ointment application does not affect the immediate response to vaccination, generation of immune memory or humoral and cell-mediated immunity.


Subject(s)
Dermatitis, Atopic/immunology , Immunosuppressive Agents/adverse effects , Meningococcal Infections/immunology , Meningococcal Vaccines/immunology , Tacrolimus/adverse effects , Administration, Topical , Antigens, CD/immunology , Child , Child, Preschool , Dermatitis, Atopic/drug therapy , Double-Blind Method , Female , Humans , Immunity, Cellular/drug effects , Immunoglobulin Isotypes/immunology , Immunologic Memory/drug effects , Male , Meningococcal Infections/prevention & control , Neisseria meningitidis, Serogroup C
8.
Br J Dermatol ; 152(4): 765-72, 2005 Apr.
Article in English | MEDLINE | ID: mdl-15840111

ABSTRACT

BACKGROUND: Basal cell carcinoma (BCC) may be difficult to treat by conventional means, particularly if the lesions are large or located in the mid-face (H-zone). Photodynamic therapy (PDT) using topical methyl aminolaevulinate (MAL) may be a good noninvasive option for these patients. OBJECTIVES: To investigate the efficacy and safety of PDT using MAL for BCCs defined as 'difficult to treat', i.e. large lesions, in the H-zone, or in patients at high risk of surgical complications. METHODS: This was a prospective, multicentre, noncomparative study. Patients were assessed 3, 12 and 24 months after the last PDT treatment. One hundred and two patients with 'difficult-to-treat' BCC were treated with MAL PDT, using 160 mg g(-1) cream and 75 J cm(-2) red light (570-670 nm), after lesion preparation and 3 h of cream exposure. Results Ninety-five patients with 148 lesions were included in the per protocol analysis. The histologically confirmed lesion complete response rate at 3 months was 89% (131 of 148). At 12 months, 10 lesions had reappeared, and therefore the cumulative treatment failure rate was 18% (27 of 148). At 24 months, an additional nine lesions had reappeared, resulting in a cumulative treatment failure rate of 24% (36 of 148). The estimated sustained lesion complete response rate (assessed using a time-to-event approach) was 90% at 3 months, 84% at 12 months and 78% at 24 months. Overall cosmetic outcome was judged as excellent or good in 79% and 84% of the patients at 12 and 24 months, respectively. Follow-up is continuing for up to 5 years. CONCLUSIONS: MAL PDT is an attractive option for 'difficult-to-treat' BCC. Because of the excellent cosmetic results, the treatment is particularly well suited for lesions that would otherwise require extensive surgical procedures.


Subject(s)
Aminolevulinic Acid/analogs & derivatives , Aminolevulinic Acid/administration & dosage , Carcinoma, Basal Cell/drug therapy , Photochemotherapy/methods , Photosensitizing Agents/administration & dosage , Skin Neoplasms/drug therapy , Administration, Topical , Adult , Aged , Aged, 80 and over , Aminolevulinic Acid/adverse effects , Carcinoma, Basal Cell/pathology , Female , Humans , Male , Middle Aged , Patient Satisfaction , Photochemotherapy/adverse effects , Photosensitizing Agents/adverse effects , Prospective Studies , Risk Factors , Skin Neoplasms/pathology , Time Factors , Treatment Failure , Treatment Outcome
9.
J Chromatogr A ; 1006(1-2): 45-60, 2003 Jul 18.
Article in English | MEDLINE | ID: mdl-12938875

ABSTRACT

An analytical method for computing the residence time distribution of the liquid distribution system in chromatography columns is described. The impact of the distributor design on the separation efficiency is predicted as a function of media properties and packed bed dimensions. The efficiency loss due to the distributor when increasing column diameter during scale-up is quantified. It is shown that this loss can be compensated by modulating the local bed height via a moderate inclination of the bed support. It is concluded that the selection of an appropriate distributor design concept with optimised dimensions enables a scale-up of chromatographic separations without any significant loss of chromatographic efficiency due to the distribution system.


Subject(s)
Chromatography/instrumentation , Models, Theoretical
10.
J Am Acad Dermatol ; 44(5): 807-13, 2001 May.
Article in English | MEDLINE | ID: mdl-11312429

ABSTRACT

BACKGROUND: Superficial basal cell carcinoma (sBCC) is an increasingly common tumor in fair-skinned populations throughout the world. Imiquimod, an immune response modifier that induces cytokines including interferons, has been shown in preliminary studies to have an effect when applied topically to BCC. OBJECTIVE: We conducted a multicenter, randomized, open-label dose-response trial of imiquimod 5% cream in the treatment of primary sBCC assessing efficacy and safety of different dose regimens. METHODS: Ninety-nine patients were randomized to 6 weeks' application of imiquimod in 1 of 4 treatment regimens: twice every day, once every day, twice daily 3 times/week, once daily 3 times/week. The treatment site was excised and examined histologically 6 weeks after cessation of imiquimod. RESULTS: Intention-to-treat analysis revealed 100% (3/3) histologic clearance in the twice-daily regimen, 87.9% (29/33) clearance in the once every day regimen, 73.3% (22/30) clearance in the twice-daily 3 times/week regimen, and 69.7% (23/33) clearance in the once-daily 3 times/week regimen. Dose-related inflammatory skin reactions at the site of application were common. The majority were well tolerated and only 1 patient withdrew from the trial as a result of a medication-related skin reaction. CONCLUSION: Imiquimod 5% cream appears to have potential as a patient-administered treatment option in sBCC.


Subject(s)
Aminoquinolines/administration & dosage , Antineoplastic Agents/administration & dosage , Carcinoma, Basal Cell/drug therapy , Skin Neoplasms/drug therapy , Administration, Topical , Adult , Aged , Aged, 80 and over , Australia , Dose-Response Relationship, Drug , Drug Administration Schedule , Female , Humans , Imiquimod , Male , Middle Aged , New Zealand , Treatment Outcome
11.
Am J Clin Dermatol ; 1(3): 187-9, 2000.
Article in English | MEDLINE | ID: mdl-12094771
12.
Med Pregl ; 52(9-10): 343-50, 1999.
Article in Croatian | MEDLINE | ID: mdl-10624382

ABSTRACT

INTRODUCTION: This paper deals with basic rational antiepileptic therapeutic procedures in children with special consideration of numerous specificities which occur in childhood: difficulties in establishing correct syndrome diagnosis, predominantly after the first or first few seizures which makes it difficult to decide about appropriate syndrome-specific therapy in regard to efficacy, mechanism of action and range of antiepileptic action; difficulties in assessment of subjective factors (their adverse effects and recognition of seizures with subjective symptoms), children's vulnerability in regard to drug toxicity; age-specific pharmacokinetics of these drugs. MATERIAL AND METHODS: The number of available antiepileptics today is great due to new drugs, but carbamazepine (CBZ) and valproate (VAL) are still basic antiepileptics, although carbamazepine's action is reduced to partial epilepsies. The paper describes range of action of available antiepileptics in regard to classification of epileptic seizures and most frequent epileptic syndromes. DISCUSSION: Adverse effects of antiepileptic agents depend on the age, so examples of age-dependent adverse effects are given considering conventional and new antiepileptics. It is well known that optimal control of seizures depends not only on correct choice of drug, but also on appropriate dosage; it is necessary to be informed about age-dependent characteristics of clinical pharmacokinetics: resorption, metabolism, elimination and half-life of antiepileptics. Although 70-80% of children may be well treated with monotherapy, 15% of children require combination of 2 or more drugs causing drug interactions in resorption, distribution, metabolism and elimination. Examples of antiepileptic interactions as well as interactions of other drugs and antiepileptics are given. The paper also deals with special importance of the psychosocial aspects of epilepsy. These children are often unaccepted by others, mostly because others are afraid of their disease, which contributes to poor quality of life of these children. Development of intellectual, emotional functions, physical development and socialization, apart from affecting the choice of drug, make epilepsy treatment in children more complex, with special emphasis on mental-hygienic aspects of complete management of children. CONCLUSION: Only a complex approach to child suffering from epilepsy may provide optimal development, quality of life improvement and complete social integration. Rational therapy of epilepsy in children requires good knowledge not only of age-specific syndromes, clinical pharmacology of anticonvulsants, their efficacy and range of action, but also specificity of their metabolism in children, profile of adverse effects as well as facing numerous nonmedical problems.


Subject(s)
Anticonvulsants/therapeutic use , Epilepsy/drug therapy , Anticonvulsants/adverse effects , Child , Humans
13.
J Nucl Med ; 39(5): 849-56, 1998 May.
Article in English | MEDLINE | ID: mdl-9591588

ABSTRACT

UNLABELLED: The purpose of our study was to compare the results of planar and SPECT scintimammography for the detection of breast carcinoma. In addition, our goal was to determine whether SPECT reconstructed with filtered backprojection (FBP) or with iterative algorithms (ISA) can improve the sensitivity and specificity of planar scintimammography (SMM). METHODS: One hundred thirteen patients with suspicious physical examinations and/or mammography underwent planar lateral and anterior breast imaging as well as SPECT imaging after injection of 99mTc-sestamibi. We used a blind evaluation, both separately and combined, for planar SMM, ISA-SPECT and FBP-SPECT. Scintigraphic findings were correlated with the final histopathological diagnoses. RESULTS: The sensitivity of planar SMM was 80% with a specificity of 83%. All ISA-SPECT studies were of diagnostic quality, while FBP-SPECT was considered nondiagnostic in 14 that were excluded for statistical calculation. Sensitivity of ISA-SPECT and FBP-SPECT were 71% and 69%, respectively. Specificity was 70% for ISA-SPECT and 66% for FBP-SPECT. Combined planar SMM plus ISA-SPECT sensitivity was 85% (81% for planar SMM plus FBP-SPECT) with a specificity of 72%. Three carcinomas indeterminate on planar SMM were correctly identified by combined planar SMM plus ISA-SPECT. ISA-SPECT and FBP-SPECT provided additional information to planar SMM with respect to localization of sestamibi uptake, tumor extent, improved diagnostic certainty and detection of axillary nodes in 40 and 14 patients, respectively. CONCLUSION: ISA reconstruction is the preferable approach to SPECT data. Combined with planar SMM, ISA-SPECT can improve sensitivity. SPECT is useful in cases of indeterminate and positive planar SMM.


Subject(s)
Algorithms , Breast Neoplasms/diagnostic imaging , Image Processing, Computer-Assisted/methods , Radiopharmaceuticals , Technetium Tc 99m Sestamibi , Tomography, Emission-Computed, Single-Photon , Breast Diseases/diagnostic imaging , Breast Diseases/epidemiology , Breast Neoplasms/epidemiology , Female , Humans , Middle Aged , Predictive Value of Tests , Prospective Studies , Sensitivity and Specificity , Tomography, Emission-Computed, Single-Photon/methods
14.
Biotechnol Bioeng ; 54(2): 181-9, 1997 Apr 20.
Article in English | MEDLINE | ID: mdl-18634085

ABSTRACT

High capacity membrane adsorbents have been used as a stationary phase for the preparative chromatographic purification of human serum albumin. A two-step ion exchange fractionation scheme yields albumin with 98% purity from clarified, microfiltrated, and desalted human plasma. Experiments with laboratory and pilot scale membrane modules are compared to literature data obtained with conventional Fast Flow Sepharose in a similar purification protocol. Increased productivity in combination with excellent reproducibility and stability was found using the membrane adsorbents. Scale-up of the process based on standard microfiltration equipment was successful but resulted in reduced capacity and productivity due to deteriorated flow characteristics of the module. This was attributed to the effects of substantial axial dispersion in the pilot scale module. Methods to reduce this limitation were identified. The concept of membrane adsorption chromatography for the fast purification of proteins is illustrated and engineering aspects important for the process design are discussed.

15.
Prax Kinderpsychol Kinderpsychiatr ; 46(3): 182-94, 1997 Mar.
Article in German | MEDLINE | ID: mdl-9190579

ABSTRACT

In order to deal with physical aggression in schools it is necessary to develop an educational concept in which the teachers parallel to their observations of the subject orientated learn-track include the relationship- and the self-development-track (three-track-education). In this concept of classifying dialogs which follow the conflict situations have equal importance to other events during school-lessons. The dialogs take place parallel to the lessons. This method requires a flexible organisation of the lessons in which the pupils are used to work on their own. An extension of the teachers competence is necessary. The extension of competence is related to a close observation of social events and to a development of models to explain the problematic behavior of pupils. If it becomes possible for example to interpret part of the pupils' behavior as scenic acting this new point of view may lead to new solutions. The educational concept is orientated on a model of psychoanalytical explanation in which the current situation stands in the foreground. The problem which thus becomes apparent can be now be handled by reconstructing the exterior events (interactions) and by the symbolic presentation of the interior perception (annoyance, anger, rage). Thus the pupils learn to deal with their inner turbulences in the constructive manner. For the acting in the public forms of making amends are practised. Physical aweness and fitness is seen as an important base for self- and social processes. The work of a man within a boys' group and of a woman within a girls' group offers the possibility of sexual identity.


Subject(s)
Health Education , Personality Development , Self Concept , Socialization , Violence/prevention & control , Adolescent , Adult , Aggression/psychology , Child , Female , Humans , Internal-External Control , Male , Problem Solving , Psychotherapy, Group , Violence/psychology
16.
Article in German | MEDLINE | ID: mdl-8868528

ABSTRACT

AIM: The aim of this study was to investigate the influence of intranasally administered midazolam in different doses on spontaneous respiration in children. METHODS: 40 children received in randomised order 0.2, 0.4 or 0.6 mg/kg b.w. midazolam intranasally or NaCl 0.9% as control. 10 minutes later, anaesthesia was induced by inhalation of halothane, nitrous oxide and oxygen. The children were breathing spontaneously at a PEEP of 5 cm H2O on a circle system with a fresh gas flow of 61/min (FIO2 = 0.33). Intubation was performed in deep anaesthesia without muscle relaxant. Halothane concentration was reduced to an endtidal concentration of 0.4 Vol%. With a baby pneumotachograph, minute ventilation, tidal volume, peak inspiratory and expiratory flow and respiratory rate were recorded during quiet breathing. Endtidal pCO2 was measured. Ventilation was then stimulated with 0.2 and 0.41/min CO2 and the same parameters were recorded. Regression analysis was performed for minute ventilation and endtidal pCO2 to obtain the slope which is a parameter for the sensitivity of the chemoreceptor mediated control of ventilation. RESULTS: The tidal volume and peak inspiratory flow were significantly reduced for a dose of 0.6 mg/kg compared to the control group. No statistical difference could be found for any other parameter between the control and study groups. CONCLUSION: We conclude that nasally administered midazolam reduces tidal volume and inspiratory peak flow in spontaneously breathing children at a dose of 0.6 mg/kg b.w. compared to control during halothane--nitrous oxide--oxygen anaesthesia. The CO2 mediated control of respiration under this condition is preserved.


Subject(s)
Midazolam/administration & dosage , Preanesthetic Medication , Respiration/drug effects , Administration, Intranasal , Anesthesia, General , Anesthesia, Inhalation , Child , Child, Preschool , Dose-Response Relationship, Drug , Female , Humans , Infant , Male , Midazolam/adverse effects
17.
Med Pregl ; 49(11-12): 479-82, 1996.
Article in Croatian | MEDLINE | ID: mdl-9019632

ABSTRACT

Von Willebrand's disease seems to be the most common hereditary bleeding disorder in children. Every form of this disease is based on quantitative or qualitative disorder of von Willebrand's factor influencing adhesion of thrombocytes (primary hemostasis) and stabilization FVIII:C in circulation (secondary hemostasis). We present contemporary knowledge on epidemiologic investigations, molecular biology, classification and rational diagnostic approach to von Willebrand's disease in children. We also report on evaluating laboratory tests' reliability in 51 examined children with von Willebrand's disease. It can be concluded that most laboratory tests are highly specific and significant for diagnosis. Determination of vWF activity has optimal value for establishing laboratory diagnosis of von Willebrand's disease; RIPA and multimer analysis are valuable for subtype classification.


Subject(s)
von Willebrand Diseases/diagnosis , Adolescent , Child , Child, Preschool , Female , Humans , Infant , Male , von Willebrand Diseases/blood
20.
Contact Dermatitis ; 27(4): 214-9, 1992 Oct.
Article in English | MEDLINE | ID: mdl-1451485

ABSTRACT

To elucidate further the natural history and prognosis of occupational chromate dermatitis, 120 affected patients, diagnosed between 1980 and 1989, were reviewed. The incidence of chromate dermatitis in Western Australia appeared to remain unchanged over the decade. 65% of patients were construction workers with cement-induced chromate dermatitis. Workers at greatest risk of sensitization were those mixing bagged cement at the work site. The median age at onset of symptoms was 34 years, with 48% having been exposed to chromate for 5 years or less. Only 37% presented to the dermatologist within 12 months of developing symptoms. 76% of patients had ongoing dermatitis at the time of review. Although 48% of the study population had completely changed their occupation to avoid chromate exposure, symptoms persisted in 69%. A delayed diagnosis of chromate sensitivity was noted to be a predictor of chronicity. In view of the potential chronicity of chromate dermatitis and its associated social and occupational impairment, we recommend the addition of ferrous sulphate while mixing bagged cement at the work site. This simple technique targets the workers at greatest risk of becoming sensitized.


Subject(s)
Chromates/adverse effects , Dermatitis, Occupational , Adolescent , Adult , Dermatitis, Occupational/diagnosis , Dermatitis, Occupational/etiology , Humans , Middle Aged , Prognosis
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