Guideline Promotion Increases Prescription of Bone Protection with Steroids in Hospitalised Patients.

Guidelines for the prevention of glucocorticoid (GC) induced osteoporosis (GIOP) were implemented in a level 5 Irish Hospital with cross sectional audit of inpatient prescribing undertaken before and after. Prior to guideline implementation, elemental calcium (Ca) with Vitamin D (VitD) was prescribed for 11/66 (17%) of patients on GCs with 2/66 (3%) also receiving bisphosphonate (BP) therapy. Subsequent to guideline implementation, Ca with VitD was prescribed for 19/55 (35%) of patients on GCs with 11/55 (20%) also receiving BP therapy, representing a 2 and 6 fold respective increase. Internal promotion of guidelines is an effective strategy for healthcare improvement but needs refinement with or without repetition to achieve better patient outcomes.

Osteogenesis imperfecta in adults: phenotypic characteristics and response to treatment in an Irish cohort.

BACKGROUND: Osteogenesis imperfecta (OI) is a heritable disorder of variable phenotype that is characterised by bone fragility and frequent fractures, with deformities and short stature in more severe cases. AIMS: We sought to review the response to treatment in a cohort of adult patients with OI. METHODS: Charts of 16 patients with OI attending a metabolic bone disease clinic were reviewed, particularly with respect to the response to treatment using bisphosphonates and recombinant human parathyroid hormone (rhPTH). The response to treatment was assessed by monitoring bone mineral density (BMD) and bone turnover markers (BTMs). RESULTS: In response to bisphosphonate therapy, median (range) BMD increased at the spine by 15.1(6.9-43.7) %. In response to rhPTH in 2 cases, spinal BMD increased by 40.3 and 27.2 %. CONCLUSION: OI is debilitating disorder, but the course of the disease may be altered by treatment that increases BMD such as bisphosphonates and rhPTH. Both serial BMD and BTM aid in assessing response to intervention. Further study is needed with regard to fracture prevention.

Stereological estimation of epidermal volumes and dermo-epidermal surface area in normal skin.

Quantitative morphological studies of the healthy epidermis are essential in providing a range of parameter estimates that can be considered within the range of normality. Stereology is a set of statistical tools that provides potentially unbiased and precise estimates of 3-dimensional tissue characteristics from 2-dimensional sections. We set out to establish reference values for the volume of the viable epidermis contained within a four-millimetre punch biopsy (V(epi)), the volume of the stratum corneum (V(SC)) and the surface area of the dermo-epidermal junction(A(DEJ)) in 4 predetermined body regions by use of stereology. Four-millimetre punch biopsies were taken from 20 freshly diseased corpses, fixed in formalin and embedded in paraffin. V(epi), V(SC) and A(DEJ) were established stereologically for all 4 body locations followed by pairwise comparison of means after Bonferroni correction. V(epi) was significantly larger in the sole compared to all other body locations (p < 0.01). Furthermore, linear regression analysis showed a strong linear relationship between V(epi) and V(SC) in the sole (r = 0.70). Our results suggest that the viable layers of the epidermis might also serve a mechanical function, either directly or by providing the stratum corneum with keratinocytes to support the hyperkeratosis in the weight-bearing parts of the skin.

Hidradenitis suppurativa: a disease of the absent sebaceous gland? Sebaceous gland number and volume are significantly reduced in uninvolved hair follicles from patients with hidradenitis suppurativa.

BACKGROUND: The pathogenesis of hidradenitis suppurativa (HS) is not clearly understood. The nomenclature suggests an important role for the apocrine glands but recent evidence implicates the pilosebaceous unit as a more likely candidate to play a central role in the pathogenesis. OBJECTIVES: Our aim was to estimate the volume of the follicular epithelium, the follicular lumen and the sebaceous glands of patients with HS and healthy controls by means of stereology. METHODS: Four-millimetre punch biopsies were taken from 21 patients with HS and nine healthy controls, fixed in formalin, embedded in paraffin and stained with haematoxylin and eosin prior to volume estimation using the Cavalieri principle. RESULTS: Sebaceous gland tissue could be visualized in only 10 of 15 suitable hair follicle biopsies from patients with HS but was present in all biopsies from healthy controls (P = 0·05) and the mean sebaceous gland volume per follicle was one-seventh of that of healthy controls (P = 0·03). There was no significant difference between patients with HS and healthy controls with regard to follicular epithelium and follicle lumen volume. CONCLUSIONS: Our results suggest that the absence or reduced volume of the sebaceous gland may play a role in the pathogenesis of HS. The presence of fibrosis suggests that sebaceous glands are obliterated early in the pathogenesis of HS.

Hans Christian Jacobaeus: Inventor of human laparoscopy and thoracoscopy.

Hans Christian Jacobaeus performed the first clinical laparoscopic surgery in Stockholm. This pioneering procedure was based on the animal experiments of Georg Kelling (1866-1945), a German physician from Dresden, who performed the first laparoscopic intervention in 1901 using a Nitz cystoscope in a dog. In 1910, Jacobaeus published his initial experiences with laparoscopic surgery in the Münchner Medizinischen Wochenschrift under the title "The Possibilities for Performing Cystoscopy in Examinations of Serous Cavities." He used this technique for diagnostic purposes in undefined abdominal complaints and functional impairment. Jacobaeus was the first who pointed out the possibility of injuring organs, especially the intestines, by inserting the trocar. In 1910, Jacobaeus recognized the immense diagnostic and therapeutic possibilities of laparoscopic surgery, as well as its difficulties and limits. He also was the first to realize the need for initial endoscopic training in animals and corpses. He promoted the development of special laparoscopic instruments to optimize and simplify the procedure.

Molecular-weight dependence of the glass transition temperature of freely-standing poly(methyl methacrylate) films.

We have used transmission ellipsometry to measure the glass transition temperature, T(g), of freely-standing films of atactic and syndiotactic poly(methyl methacrylate) (PMMA). We have prepared films with different molecular weights, MW, (159 x 10(3) < M (w) < 1.3 x 10(6)) and film thicknesses, h, ( 30 nm < h < 200 nm). For the high-MW ( M (w) > 509 x 10(3)) atactic PMMA films, we find that T(g) decreases linearly with decreasing h, which is qualitatively similar to previous results obtained for high-MW freely-standing polystyrene (PS) films. However, the overall magnitude of the T(g) reduction is much less (by roughly a factor of three) for the high-MW freely-standing PMMA films than for freely-standing PS films of comparable MW and h. The observed differences between the freely-standing PMMA and PS film data suggest that differences in chemical structure determine the magnitude of the T(g) reduction and we discuss the possible origins of these differences. Our analysis of the MW-dependence of the T(g) reductions suggests that the mechanism responsible for the MW-dependent T(g) reductions observed in the high-MW freely-standing films is different than that responsible for the MW-independent T(g) reductions observed in the low-MW freely-standing and supported films.

[Foreign body in the urinary bladder after vascular surgery]. / Ein Corpus alienum in der Harnblase nach gefässchirurgischem Eingriff.

INTRODUCTION: We are presenting a rare complication after femorofemoral bypass surgery. CASE REPORT: In a 61-year-old male patient, a femorofemoral crossover bypass graft was inadvertently placed through the urinary bladder. Postoperatively, the patient developed macrohematuria, which cleared spontaneously. The diagnosis of an intravesical graft was made 3 months after surgery by cystoscopy performed because of dysuria. The patient underwent open bladder surgery 7 months later as he refused earlier intervention. The misplaced graft, which was not infected and showed good function and perfusion, was extravesically relocated. At a 16-month follow-up examination, the patient is free of urological symptoms and the bypass functions well. CONCLUSIONS: In case of dysuria or macrohematuria after vascular surgery in the vicinity of the urinary bladder, a misplaced bypass should be excluded.

[The role of observer for the reliability of Dutch version of the Discomfort Scale-Dementia of Alzheimer Type (DS-DAT)]. / De rol van de observator in de betrouwbaarheid van de Nederlandse versie van de Discomfort Scale-Dementia of Alzheimer Type (DS-DAT).

The role of the observer in the reliability of the Dutch Discomfort Scale-Dementia of Alzheimer Type (DS-DAT). The Discomfort Scale of Dementia of the Alzheimer Type (DS-DAT) is an instrument to assess discomfort in severely demented patients. No data on the reliability of assessment using a Dutch translation were available. In this paper, we analyse the role of the observer in the reliability of rating. This is of importance for studies in which many physicians perform multiple assessments. Twenty-eight nursing home physicians in training rated the DS-DAT in five nursing home patients with dementia presented on videotape. This was repeated after five months. All the physicians were previously trained in the use of the instrument. The results were statistically analysed using random effects analysis of variance. The Intra-class Correlation Coefficient (ICC) was 0.74 for inter-observer reliability and 0.97 for intra-observer reliability. Variance between subsequent assessments was small, but physicians appeared to differ somewhat among themselves in the way they rated the videotaped patients. A future complete reliability assessment of rating the DS-DAT in clinical practice would involve patient variation as well, scoring patients in clinical practice.

Soluble Fas and Fas-ligand in bladder cancer in vitro and in vivo.

Circulating soluble Fas (sFas) and expression of Fas-ligand on cancer cells are mechanisms of immune escape. The aim of the present study was to investigate expression and production of Fas and Fas-ligand on bladder cancer cell lines of different grade as a basic mechanism of their secretion in vivo. sFas and sFas-ligand serum levels of patients with different stage of bladder cancer were examined to determine the possible clinical use of these molecules as tumor markers. Bladder cancer cell lines RT4 (G1), RT112 (G1), T24 (G3) and SUP (G4) were analyzed by flowcytometry for Fas and Fas-ligand expression. To determine if the Fas-ligand gene is transcribed in these bladder cancer cell lines, RT-PCR was performed on mRNA extracted from these cell lines. Production of sFas and sFas-ligand was examined in cell culture supernatants of the cancer cells as well as in the serum of 62 patients with bladder cancer by a specific ELISA test. We demonstrate that Fas is expressed in similar levels on all human bladder carcinoma cell lines. In T24 (G3) and SUP (G4) cell lines we were able to detect the Fas-ligand protein, whereas no Fas-ligand protein could be found in RT4 and RT112 (G1) cells. Fas-ligand mRNA was expressed in all bladder cancer cell lines. Furthermore, all bladder cancer cell lines produce sFas but no sFas-ligand in spite of mRNA expression. The range of sFas levels in the serum of all patients with bladder cancer was large and did not show a correlation to the histopathological stage of bladder cancer. Although there is in vitro evidence that sFas and Fas-ligand play a role in bladder cancer, no correlation between the sFas and s Fas-ligand serum levels and the histopathological stage of bladder cancer could be found. Therefore, serum sFas and sFas-ligand have to date limited clinical relevance.

Bladder cancer cells acquire competent mechanisms to escape Fas-mediated apoptosis and immune surveillance in the course of malignant transformation.

Mechanisms of resistance against Fas-mediated cell killing have been reported in different malignancies. However, the biological response of immune escape mechanisms might depend on malignant transformation of cancer cells. In this study we investigated different mechanisms of immune escape in 2 well-differentiated low-grade (RT4 and RT112) and 2 poorly differentiated high-grade (T24 and TCCSUP) bladder cancer cell lines. Fas, the receptor of Fas-ligand, is expressed and shedded by human transitional bladder carcinoma cell lines RT4, RT112, T24 and TCCSUP. Cytotoxicity and apoptosis assays demonstrate that in spite of the Fas expression, poorly differentiated T24 and TCCSUP cells are insensitive towards either recombinant Fas-ligand or agonistic apoptosis-inducing monoclonal antibody against Fas. In poorly differentiated T24 and TCCSUP cell lines we were able to detect marked Fas-ligand protein by flow cytometry and Western blot analysis. In grade 1 RT4 and RT112 cells only minor expression of Fas-ligand possibly because of proteinase action. Fas-ligand mRNA translation or post-translational processing seems to be regulated differentially in the cancer cell lines depending on malignant transformation. In co-culture experiments we show that poorly differentiated cells can induce apoptosis and cell death in Jurkat cells and activated peripheral blood mononuclear cells. This in vitro study suggests that bladder cancer cells can take advantage of different mechanisms of immune evasion and become more competent in avoiding immune surveillance during transformation to higher-grade malignant disease.

[Pentoxifylline inhibits secretion of O2- and TNF-alpha by alveolar macrophages in patients with sarcoidosis]. / Pentoxifyllin hemmt die Sekretion von O2- und TNF-alpha durch Alveolarmakrophagen bei Patienten mit Sarkoidose.

Reactive oxygen species (ROS) and cytokines like tumor necrosis factor-alpha (TNF-alpha) play a crucial role as inflammatory mediators in pulmonary sarcoidosis. We examined the antiinflammatory effect of pentoxifylline (POF) on alveolar macrophages (AM) of patients with sarcoidosis in vitro. We could demonstrate that POF (above 4.10(-4) M) inhibited the secretion of superoxide anion and TNF-alpha by AM in a dose-dependent manner via a prostaglandin synthesis-dependent mechanism that was independent of the glucocorticoid receptor. POF is an interesting immunomodulating substance that should be further evaluated in clinical trials.

A rapid semiautomatical enzyme linked immunoassay identifying intercellular adhesion molecule-1 (ICAM-1) on the alveolar macrophage surface.

Intercellular adhesion molecule-1 (ICAM-1), a member of the immunoglobulin gene superfamily, is a cytokine-inducible adhesion molecule, which plays a central role in leukocyte migration into sites of acute or chronic inflammation. In this article we describe a sandwich immunoenzymometric method which allows rapid, semiquantitative (in "enzyme immunoassay units", EU) identification of ICAM-1 on the surface of alveolar macrophages. We evaluated this method in two groups of patients with pulmonary sarcoidosis (n = 12) or bacterial pneumonia (n = 11) and a group of healthy volunteers (n = 6), comparing the results with those obtained by immunocytochemical staining. ICAM-1 expression on the sarcoid alveolar macrophages surface was significantly elevated, as compared with control alveolar macrophages (0.76 EU +/- 0.27 vs. 0.44 EU +/- 0.12, p < 0.01). ICAM-1 expression on the surface of alveolar macrophages from patients with pneumonia was not elevated (0.48 EU +/- 0.35). Stimulation with tumour necrosis factor-alpha (TNF-alpha) or interferon-gamma (100 kU/l) led to a significant induction of ICAM-1 on the surface of control alveolar macrophages (0.76 EU +/- 0.18, p < 0.005 for TNF-alpha, 0.64 EU +/- 0.10, p < 0.005 for interferon-gamma), whereas alveolar macrophages from both patient groups did not respond to cytokines even at high dosages. ICAM-1 expression on the surface of alveolar macrophages from patients with sarcoidosis correlated with the spontaneous release of TNF-alpha by macrophages (R = 0.77, p < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

A short evaluation of a new haematological analyser: the Cobas Argos 5 Diff.

In order to evaluate the Cobas Argos 5 Diff, a five-part differential haematological analyser, we performed a comparative study using our current analyser, the Toa E-5000, and the manual leukocyte differential. Samples (n = 593) were collected from various departments in our hospital and were tested on both Cobas Argos 5 Diff and Toa E-5000. Regression lines were calculated for all standard haematological quantities. A group of 100 samples, including 50 negative (absence of flags) and 50 positive (presence of flags), on the Cobas Argos 5 Diff were randomly selected from the above-mentioned collection. All these samples had been checked under the microscope by two persons counting 200 cells each. The comparison of standard haematological quantities between Cobas Argos 5 Diff and the Toa E-5000 shows good correlation: Red Blood Cells r = 0.993; White Blood Cells r = 0.998; Haemoglobin r = 0.989; Haematocrit r = 0.982; Thrombocytes r = 0.988; Lymphocytes (%) r = 0.983; Neutrophils (%) r = 0.959. The correlation between Cobas Argos 5 Diff and the manual leukocyte differential shows good correlation for lymphocytes and neutrophils, with acceptable correlation for eosinophils. The correlation for basophils and monocytes was less acceptable, especially for normal samples. We conclude that the efficiency of the Cobas Argos 5 Diff is good (93%) and that it is a suitable haematological cell analyser.