[How effective is rituximab in rheumatoid arthritis?: lessons learned from clinical practice]. / Wie wirksam ist Rituximab bei der rheumatoiden Arthritis? : Erfahrungen im klinischen Alltag.

OBJECTIVES: Does experience with rituximab treatment of rheumatoid arthritis (RA) in daily clinical practice confirm the results of controlled randomized studies? METHODS: This is a retrospective data-analysis of the first 50 patients from one center with rituximab treatment for RA. The patients received at least one cycle of 2 rituximab infusions (1000 mg, respectively) within 2 weeks. Clinical assessment was performed 3-5 months after the first infusion. RESULTS: The patients were older (mean age, 59 years) as compared to previously published controlled studies. The DAS28 was lower (5.5). The mean prednisolone dose was high (13.4 mg/d). The rheumatoid factor was positive in 88% of patients. Only six patients would have fulfilled inclusion criteria for controlled studies such as prednisolone dose

Prognosis of large-vessel giant cell arteritis.

OBJECTIVE: The prognosis of large-vessel GCA (LV-GCA) has not yet been investigated. How does it compare to GCA without arm vasculitis (GCA controls)? METHODS: Charts of 53 LV-GCA patients and 53 GCA controls were reviewed following a predetermined protocol. Telephone interviews of patients or their primary care physicians were conducted. Forty LV-GCA patients underwent follow-up duplex ultrasound examinations of proximal arm arteries. RESULTS: The mean observation time was 50 (s.d. +/- 31) months. None of the LV-GCA patients developed ischaemic arm complications. In 30%, proximal arm artery wall swelling disappeared completely. It decreased in 53%. In 8% it remained unchanged, in 5% it increased and in 5% arteries occluded with collateral flow. After the start of treatment, anterior ischaemic optic neuropathy developed neither in LV-GCA patients nor in GCA controls, amaurosis fugax occurred in 4 and 6%, arterial hypertension in 53 and 66%, strokes in 9 and 9%, myocardial infarction in 2 and 2%, diabetes mellitus in 30 and 25%, osteoporosis in 38 and 23%, and osteoporotic fractures in 15 and 4%, respectively. Mean corticosteroid dose was 3.7 mg/day. Mean duration of therapy was 42 months. All differences were insignificant. Four LV-GCA patients developed vasculitic popliteal artery stenoses. CONCLUSIONS: The prognosis of LV-GCA is benign with regard to ischaemic complications. Proximal artery wall swelling decreases in most cases. Its course is similar to GCA without proximal arm arteritis.

[Which ultrasound scan is the best to detect glenohumeral joint effusions?]. / Schultergelenkerguss: Welcher Ultraschallschnitt ist der beste?

PURPOSE: It has not yet been systematically investigated which ultrasound scan is the best for detecting effusions of the glenohumeral joint. This question will be addressed by this study. Furthermore, this study determines reference values for distances to distinguish effusions from normal findings. METHODS: Ultrasound was performed according to extended DEGUM and EULAR guidelines on 200 shoulders of 100 consecutive patients with shoulder complaints and on 40 shoulders of 20 healthy controls. Distances were measured between the surface of the humerus and the joint capsule in 3 positions: Axillary recess, dorsal transverse scan with 60 degrees internal rotation and with maximum external rotation. Normal values were calculated by ROC analysis. RESULTS: The mean age of patients and controls was 58 and 55 years, and 67 % and 70 % were female, respectively. Ultrasound detected effusions in 81 shoulders of 56 patients. Effusions were seen in the dorsal scan with 60 degrees internal rotation in 30 %, in the axillary scan in 49 %, and in the dorsal scan in maximum external rotation in 94 % (p < 0.001, respectively). Five percent of the effusions were exclusively detected in the axillary scan. The upper normal limits for the distance between bone surface and joint capsule were 3.7 mm for the axillary recess, 2.7 mm for the dorsal region in 60 degrees internal rotation and 3.1 mm for the dorsal region in maximum external rotation . CONCLUSIONS: Dynamic ultrasound examination including the dorsal scan with maximum external rotation is essential for detecting glenohumeral joint effusions. The axillary scan is superior to the dorsal transverse scan with 60 degrees internal rotation.

Solid lipid nanodispersions containing mixed lipid core and a polar heterolipid: characterization.

This paper describes the characterization of solid lipid nanodispersions (SLN) prepared with a 1:1 mixture of theobroma oil and goat fat as the main lipid matrix and Phospholipon 90G (P90G) as a stabilizer heterolipid, using polysorbate 80 as the mobile surfactant, with a view to applying the SLN in drug delivery. The 1:1 lipid mixture and P90G constituting the lipid matrix was first homogeneously prepared by fusion. Thereafter, the SLN were formulated with a gradient of polysorbate 80 and constant lipid matrix concentration by melt-high pressure homogenisation. The SLN were characterized by time-resolved particle size analysis, zeta potential and osmotic pressure measurements, differential scanning calorimetry (DSC) and wide angle X-ray diffraction (WAXD). Transmission electron microscopy (TEM) and isothermal heat conduction microcalorimetry (IMC) which monitors the in situ crystallization were also carried out on the SLN containing P90G and 1.0 % w/w of polysorbate 80. The results obtained in these studies were compared with SLN prepared with theobroma oil with and without phospholipid. Particle size analysis of SLN indicated reduction in size with increase in concentration of mobile surfactant and was in the lower nanometer range after 3 months except SLN prepared without P90G or polysorbate 80. The lipid nanoparticles had negative potentials after 3 months. WAXD and DSC studies revealed low crystalline SLN after 3 months of storage except in WAXD of SLN formulated with 1.0 % w/w polysorbate 80. TEM micrograph of the SLN containing 1.0 % w/w polysorbate 80 revealed discrete particles whose sizes were in consonance with the static light scattering measurement. In situ crystallization studies in IMC revealed delayed crystallization of the SLN with 1.0 % w/w polysorbate 80. Results indicate lipid mixtures produced SLN with lower crystallinity and higher particle sizes compared with SLN prepared with theobroma oil alone with or without P90G, and would lead to higher drug incorporation efficiency when used in formulation of actives. Mixtures of theobroma oil and goat fat would be suitable for the preparation of nanostructured lipid carriers. SLN of theobroma oil containing phospholipid could prove to be a good ocular or parenteral drug delivery system considering the low particle size, particle size stability and in vivo tolerability of the component lipids. SLN prepared with lipid admixture, which had higher increase in d(90%) on storage are suitable for preparation of topical and transdermal products.

Further characterization of theobroma oil-beeswax admixtures as lipid matrices for improved drug delivery systems.

There is an increasing interest in lipid based drug delivery systems due to factors such as better characterization of lipidic excipients and formulation versatility and the choice of different drug delivery systems. It is important to know the thermal characteristics, crystal habit, texture, and appearance of a new lipid matrix when determining its suitability for use in certain pharmaceutical application. It is line with this that this research was embarked upon to characterize mixtures of beeswax and theobroma oil with a view to applying their admixtures in drug delivery systems such as solid lipid nanoparticles and nanostructured lipid carriers. Admixtures of theobroma oil and beeswax were prepared to contain 25% w/w, 50% w/w, and 75% w/w of theobroma oil. The admixtures were analyzed by differential scanning calorimetry (DSC), small angle X-ray diffraction (SAXD), wide angle X-ray diffraction (WAXD), and isothermal heat conduction microcalorimetry (IMC). The melting behavior and microstructures of the lipid admixtures were monitored by polarized light microscopy (PLM). Transmission electron microscopy (TEM) was used to study the internal structures of the lipid bases. DSC traces indicated that the higher melting peaks were roughly constant for the different admixtures, but lower melting peaks significantly increased (p < 0.05). The admixture containing 25% w/w of theobroma oil possessed highest crystallinity index of 95.6%. WAXD studies indicated different reflections for the different lipid matrices. However, new interferences were detected for all the lipid matrix admixtures between 2theta = 22.0 degrees and 2theta = 25.0 degrees. The lipid matrices containing 50% w/w and 25% w/w of theobroma oil showed absence of the weak reflection characteristic of pure theobroma oil, while there was disappearance of the strong intensity reflection of beeswax in all the lipid matrix admixtures at all stages of the study. PLM micrographs revealed differences with regard to the thermal and optical behaviors depending on the composition of the matrix. The lipid matrix consisting of 75% w/w of theobroma oil showed a spherulite texture after 4 weeks of isothermal storage. Crystallization exotherms of lipid matrices containing 50% w/w and 25% w/w of theobroma oil showed change in modification after 30 min with the latter having a greater time-dependent crystallization. Generally, low non-integral Avrami exponents and growth rate constants were obtained for all the lipid matrices, with the admixture containing 25% w/w theobroma oil having the lowest Avrami exponent and growth rate constant. Based on the results obtained, admixtures containing 50% w/w and 75% w/w of theobroma oil could be applied in the formulation of solid lipid nanoparticles and nanostructured lipid carriers as these lipid matrices possessed crystal characteristics that favour such drug delivery systems.

Laparoscopic resection for rectal cancer: outcomes in 194 patients and review of the literature.

BACKGROUND: There are few reports on laparoscopic rectum resection demonstrating its feasibility and efficacy in patients with rectal cancer. Most patient series are small, and results must be considered preliminary and medium-term. Our large prospective conducted study aimed to assess the effectiveness of a totally laparoscopic resection for rectum carcinoma with emphasis on perioperative and long-term oncological outcomes. METHODS: Between November 1992 and July 2003, 194 unselected patients were resected laparoscopically for rectal carcinoma. Patients with locally advanced rectum carcinoma (uT3/uT4) and no evidence of distant metastases were candidates for neoadjuvant chemoradiation. Adjuvant treatment was administered to patients with UICC stage II/III disease. All patients were followed up prospectively to evaluate complications and late outcomes. Survival probability analysis was performed using the Kaplan-Meier method. Study selection was made by Medline search using the following key words: rectal cancer, rectal neoplasms, laparoscopy, and resection. Single case reports and abstracts were excluded. When surgical series were reported more than once, only the most recent reports were considered and listed. RESULTS: The most common procedures were low anterior resection with total mesorectum excision in 65.5% of patients and high anterior resection in 25.3%. Average operative time was 174 min. Average number of lymph nodes removed was 25.4 and length of specimen resected was 27.6 cm. Resection was curative in 145 patients and palliative in 49 cases. UICC tumor stages were as follows: stage I: 25.2%, stage II: 27.3%, stage III: 30.4%, and stage IV: 17%. Intraoperative complications were <1% for lesions of the ureter, urinary bladder, and deferent duct. Conversion to conventional surgery was necessary in two cases (1%). The most common postoperative complication was anastomotic leakage in 13.5% of patients. There was no postoperative mortality. Follow-up evaluation ranged from 1 to 128 months with a mean of 46.1 months. The most common late complication was incisional hernia in 3.6% of patients. Port-site metastases occurred in one patient (0.5%). Tumor recurrence developed in 23 of the 145 curative resected patients (11.7% distant metastases and 4.1% local recurrence). Overall local recurrence rate was 6.7% (4.1% after curative resection and 14.3% after palliative resection). Overall survival rate was 90.6% at 1 year, 74.5% at 3 years, and 66.3% at 5 years. Overall 5-year survival rate was 76.9% after curative resection and 31.8% after palliative resection. Cancer-related survival rate was 94% at 1 year, 82.4% at 3 years, and 78.9% at 5 years. At 5 years it was 87.7% after curative resection and 48.5% after palliative resection. At 5 years, the survival rate was 100% for stage I, 94.4% for stage II, 66.6% for stage III, and 44.6% for stage IV. CONCLUSIONS: Our results and the literature review clearly demonstrate that laparoscopic resection for rectal cancer is not associated with higher morbidity and mortality. Established oncological and surgical principles are respected and long-term outcomes are at least as good as those after open surgery.

Thermal analysis of the crystallization and melting behavior of lipid matrices and lipid nanoparticles containing high amounts of lecithin.

Lipid nanoparticles (LNP) based on triglycerides containing high amounts of the amphiphilic lipid lecithin have been proposed as a promising alternative drug delivery system with regard to drug loading capacity. Aim of the present study is to evaluate the influence of lecithin within the lipid matrix (LM) on the crystallization behavior by thermoanalysis and wide angle X-ray diffraction (WAXD). The crystallinity of LM and LNP is mainly determined by the triglyceride content. However, lecithin influences the crystallization behavior significantly. WAXD shows an accelerated polymorphic transition of the LM to the beta-modification upon storage with increasing lecithin content. Both, the melting point and the crystallization temperature are not affected by the lecithin concentration and are comparable to recrystallized triglyceride bulk. However, the crystallinity indices (CI) of LM show a general decrease by 10% suggesting an incomplete crystallization. For the formation of LNP at least 10% lecithin is necessary and all systems are present in the stable beta-modification. In comparison to the undispersed LM, the crystallization temperature of LNP is significantly decreased by about 20 degrees C whereas the melting point is reduced by about 5 degrees C only. Melting enthalpy is comparable to the untreated triglyceride bulk and elevated in comparison to the undispersed LM. Isothermal heat-conduction microcalorimetry (IMC) enables the determination of crystallization kinetics after fitting of the heat flow volume according to the Avrami equation.

[Use of SPIO-enhanced T1- and T2-weighted images for the differentiation of liver lesions: an ROC analysis]. / Differenzierung von Leberläsionen mit SPIO-gestützten T1-w und T2-w MRT-Aufnahmen: Eine ROC-Analyse.

PURPOSE: The superparamagnetic iron oxide (SPIO) Resovist is a contrast media with shortening of both T(1) and T(2) relaxation time. This study evaluates the impact of SPIO-enhanced T(1)- and T(2)-weighted images for the differentiation of liver lesions. MATERIALS AND METHODS: SPIO-enhanced MRI examinations (1.5 T, Symphony Quantum) of 61 patients were analyzed. Thirty-seven patients had malignant liver lesions (metastases n = 32, HCC n = 5) proven by biopsy or laparotomy, 11 patients had benign liver lesions (FNH n = 2, hemangiomas n = 4, benign cysts n = 5, normal liver on laparoscopy n = 13). After unenhanced T(1)- and T (2)-weighted imaging, a bolus injection of 1.4 ml SPIO (Resovist) was given, followed by T(1)-weighted imaging at 20 s, 60 s, and 5 min and T(2)-weighted imaging at 10 min post injection. A score from 1 (benign) to 5 (malignant) was used by three blinded radiologist for the ROC analysis of the unenhanced T(1)-/T(2)-weighted images (set 1) and of the combinations of unenhanced T(1)/T(2)-weighted and SPIO T(1)-weighted images (set 2), unenhanced T(1)/T(2) and SPIO T(2)-w images (set 3) and all images (set 4). RESULTS: The accuracy of plain MRI (set 1: 56 %) was increased by SPIO-enhanced T(1)-weighted images (set 2: 81 %) and SPIO-enhanced T(2)-weighted images (set 3: 90 %). Best results were obtained using unenhanced T(1)-weighted, unenhanced T(2)-weighted and both SPIO T(1)-weighted and T(2)-weighted images (set 4: 93%). The accuracy of predicting histopathologic diagnosis was 91%. CONCLUSION: For the differentiation of liver lesions, SPIO-enhanced T(2)-weighted images had a greater impact on the accuracy of MRI than T (1)-weighted images, but SPIO-enhanced T(1)-weighted images provided additional information in some patients and should not be deleted.

A sensitive TLC method to identify Echinaceae pallidae radix.

In this work a fast, simple and sensitive qualitative TLC method was developed to identify Echinaceae pallidae radix and to distinguish this drug from similar ones. The TLC method is based on the lipophilic compounds of E. pallida. Three mobile phases provided good separation, e.g. toluene/ethylacetate 7 + 3 (v/v). A marker substance was found which shows a blue fluorescence at an excitation wavelength of 366 nm after detection with a spray agent containing 95 volume parts ethanol 96%, 5 parts trifluoroacetic acid 99% and zinc ions in 0.15 molar concentration. After spraying the chromatogram was heated at 110 degrees C for 7 min. This method is superior to HPLC methods to characterise mixtures of Echinacea extracts in terms of selectivity due to this post-chromatographic derivatisation and subsequent fluorescence detection.

[What sociomedical significance has the mortality from breast cancer for a mammographic preventive strategy?]. / Welche sozialmedizinische Bedeutung hat die Mortalität des Brustkrebses für eine mammographische Präventivstrategie?

Mortality is seen as the most significant criterium for the prognosis of the disease in a population and with respect to the effectiveness of prophylactic and therapeutic measures. The extraordinary high-mortality from breast carcinoma causes more psychological strain for women in working age. Breast carcinoma is the most frequent cause of death between the ages of 40 and 60 in the population of the GDR. Relevant data are the sex and age related mortality. From its reduction the cost and benefit for secondary prevention and especially of mammography can be evaluated.

[Free serum amino acids in patients with tumors of different sites--tumor-induced imbalances]. / Freie Serumaminosäuren bei Patientinnen mit Malignomen unterschiedlicher Lokalisation--tumorbedingte Imbalanzen.

We analysed 10 free serum amino acids of altogether 8 different malignant organ localisations before therapy and compared this with reference levels. We investigated asparaginic acid, glutaminic acid, glycine, alanine, valine, methionine, leucine, isoleucine, tyrosine and phenylalanine. All investigated amino acids with the exception of methionine show an elevated level compared to normal one. After successful therapy the elevated levels returned to normal ones and could be found increased in recurrent diseases. The analysis of amino acids in serum is a good method in therapeutic monitoring.

[Use of free serum amino acids in therapy monitoring of patients with treated vulvar cancer]. / Zur Anwendung freier Serumaminosäuren im Therapiemonitoring bei Patientinnen mit behandeltem Vulvakarzinom.

We investigated the value of 10 free serum amino acids in continuous therapy monitoring in 9 patients with primary cancer of vulva stag pT1-2pN0M0. In comparison with the normal we found elevated significantly asparginic acid, glutaminic acid, glycine, alanine, valine, isoleucine, leucie, phenylalanine and tyrosine. Serum level of methionine not elevated was. After primary therapy all values returned to normal within of 6 months. A posttherapeutic monitoring with helf free serum amino acids is possible.

[Social sequelae and problems following apoplexy]. / Soziale Folgen und Probleme nach Apoplexie.

162 patients with stroke (cerebrovascular accident) were investigated of some social problems. The patients were treated in two internal clinics or in a rehabilitation center for stroke-patients. The assessments were accomplished in 30 months after clinical treatment. The average of age was 69 years. The percentage of women was 61%. The majority of patients lives in own flats, 12% in a nursing home. The furniture of flats, was often not approximated for disabled persons. The care almost was undertaken through relatives. More institutional support could be helpful in few cases. Help was wished in according to conditions of flats, meals on wheels, programs for self-activities, references to nursing, technical helpings and transportation services. These investigations suggest that the families are an important factor in rehabilitation of stroke. They need social and psychological support. The attitude of family determinated essential the prognosis of rehabilitation.

[Cytologic urine findings in female genital cancer--before, during and after radiotherapy]. / Zytologische Urinbefunde bei weiblichen Genitalkarzinomen--vor, während und nach Strahlentherapie.

74 cytologic examinations of the urinary sediment were conducted on 57 women with malignant neoplasms of the genital organs in order to evaluate the clinical suspicion of tumor infiltration of the bladder wall. It turned out to be a sensitive indicator of the infiltration of the bladder wall. Prior radiotherapy however let to changes which could be falsly interpreted as indicators of malignant infiltration. In order to enhance the accuracy of cytologic evaluation of the urinary sediment in this clinical setting it is essential that the cytologist must be informed about prior radiation therapy.

[Radiotherapy of uterine cancer. A retrospective study]. / Die Strahlentherapie des Korpuskarzinoms. Eine retrospektive Studie.

96 women with primary carcinoma corporis uteri and 79 women after surgery were treated between 1965-1970 with different radiotherapeutic methods, in some cases in combination with cytostatics and gestagens. In the group of primary radiation best results are obtained with combination of intracavitary brachytherapy and external radiation (55% 5-year-survival), and in the postoperative group with external radiation alone (67% 5-year-survival). Late complications with 17% fibrosis in the parametrial tissue and 12% persistent diarrhoea in the postoperative group needs more individualization in therapy. This requires exact knowledge about extention and biological behaviour of the tumor.

[Rehabilitation in cerebrovascular stroke--experiences and results of a treatment concept based on modern neurophysiology knowledge]. / Die Rehabilitation des zerebrovaskulären Insults--Erfahrungen und Ergebnisse einer Behandlungskonzeption auf der Basis moderner neurophysiologischer Erkenntnisse.

The modern concept of rehabilitation of patients with stroke is based on new neurophysiological investigations about processes of movements, learning and memory. Therefore the rehabilitation is multidimensional. The complete patterns of symptoms must be considered. The training of cognitive functions has the same importance as the treatment of disorders of movements. The effects of this concept are investigated in 295 patients in accordance with self-activities and ability of walking. The results have been compared with 101 patients without consideration of all gnostic defects. The results of the modern rehabilitation concept were better. Patients with aphasia having similar good results but patients with diminished ability to cooperation having unfavourable prognosis of rehabilitation.

[The clinico-diagnostic value of C-reactive protein, determined by simple radial immunodiffusion and compared with latex agglutination]. / Der klinisch-diagnostische Wert des C-reaktiven Proteins (CRP), bestimmt in der einfachen radialen Immundiffusion (RID) und verglichen mit der Latexagglutination.

Importance of CRP-determination in rapid diagnosis of septic diseases in children is being examined. Specificity and sensitivity of white blood cell count, thrombocyte count, blood sedimentation rate, differential blood count and CRP were evaluated statistically. Rapid diagnosis was performed with sera of 95 patients shortly after being admitted on ward. The values of children with serious bacterial diseases were compared with those of children with serious abacterial ones. Significant superiority of CRP was established. To be successful a rapid and simple method must be available. In our study combined measurement of CRP by latex agglutination and RID has turned out to be advantageous for early detection of bacterial infection.

Standard reference values for musculoskeletal ultrasonography.

OBJECTIVES: To determine standard reference values for musculoskeletal ultrasonography in healthy adults. METHODS: Ultrasonography was performed on 204 shoulders, elbows, hands, hips, knees, and feet of 102 healthy volunteers (mean age 38.4 years; range 20-60; 54 women) with a linear probe (10-5 MHz; Esaote Technos MP). Diameters of tendons, bursae, cartilage, erosions, hypoechoic rims around tendons and at joints were measured with regard to established standard scans. Mean, minimum, and maximum values, as well as two standard deviations (2 SD) were determined. Mean values +/-2 SD were defined as standard reference values. RESULTS: Hypoechoic rims were normally present in joints and tendon sheaths owing to physiological synovial fluid and/or cartilage. Similarly, fluid was found in the subdeltoid bursa in 173/204 (85%), at the long biceps tendon in 56 (27%), in the suprapatellar recess in 158 (77%), in the popliteal bursae in 32 (16%), and in the retrocalcaneal bursa in 49 (24%). Erosions of >1 mm were seen at the humeral head in 47 (23%). Values for important intervals were determined. The correlation between two investigators was 0.96 (0.78-0.99). The reliability of follow up investigations was 0.83 (0.52-0.99). CONCLUSIONS: Fluid in bursae as well as hypoechoic rims within joints and around tendons are common findings in healthy people. This study defines standard reference values for musculoskeletal ultrasonography to prevent misinterpretation of normal fluid as an anatomical abnormality.