Influence of Promotion on the Growth of Anchored Colloidal Iron Oxide Nanoparticles during Synthesis Gas Conversion.

Using colloidal iron oxide nanoparticles with organic ligands, anchored in a separate step from the supports, has been shown to be beneficial to obtain homogeneously distributed metal particles with a narrow size distribution. Literature indicates that promoting these particles with sodium and sulfur creates an active Fischer-Tropsch catalyst to produce olefins, while further adding an H-ZSM-5 zeolite is an effective way to obtain aromatics. This research focused on the promotion of iron oxide colloids with sodium and sulfur using an inorganic ligand exchange followed by the attachment to H-ZSM-5 zeolite crystals. The catalyst referred to as FeP/Z, which consists of iron particles with inorganic ligands attached to a H-ZSM-5 catalyst, was compared to an unpromoted Fe/Z catalyst and an Fe/Z-P catalyst, containing the colloidal nanoparticles with organic ligands, promoted after attachment. A low CO conversion was observed on both FeP/Z and Fe/Z-P, originating from an overpromotion effect for both catalysts. However, when both promoted catalysts were washed (FeP/Z-W and Fe/Z-P-W) to remove the excess of promoters, the activity was much higher. Fe/Z-P-W simultaneously achieved low selectivity toward methane as part of the promoters were still present after washing, whereas for FeP/Z-W the majority of promoters was removed upon washing, which increased the methane selectivity. Moreover, due to the addition of Na+S promoters, the iron nanoparticles in the FeP/Z(-W) catalysts had grown considerably during catalysis, while those in Fe/Z-P(-W) and Fe/Z(-W) remained relatively stable. Lastly, as a large broadening of particle sizes for the used FeP/Z-W was found, where particle sizes had both increased and decreased, Ostwald ripening is suggested for particle growth accelerated by the presence of the promoters.

The standardised mortality ratio: the proper quality indicator in acute leukaemia?

BACKGROUND: The standardised mortality ratio (SMR) is a quality indicator used to measure quality of care in the Netherlands. It is subject to much criticism, which was the reason to study the value of the SMR as a quality indicator for the treatment of acute leukaemia. METHODS: A retrospective analysis was performed in patients with acute leukaemia admitted to a Santeon hospital during the period 2005-2009. SMR values were calculated and compared with the overall survival (OS). RESULTS: During the study period, 455 unique patients were admitted with acute leukaemia. SMR calculation was based on 992 admissions. SMR analysis yielded a high mortality ratio in hospital 1, 2, 3 and 4 in comparison with the national average (100), significant for hospital 1 and 4 (180 [CI 95% 126-257] and 187 [CI 95% 134-261], respectively) OS analysis also showed a significantly different outcome between hospitals. However, using OS as outcome parameter, hospital 2 and 6 showed the lowest performance as compared with hospital 1 and 4 using SMR as parameter. After multivariate analysis, age (HR 1.04; CI 95% 1.03-1.05; p < 0.001) and hospital (hospital 5 compared with 6: HR 0.54; CI 95% 0.30- .98; p = 0.043; hospital 2 compared with 1: HR 1.51; CI 95% 1.02-2.23; p = 0.039) were the only significant variables that influenced OS. CONCLUSION: Outcome according to SMR is not equivalent to outcome according to OS. This study shows that the use of the SMR as a quality indicator for the treatment of acute leukaemia does not appear to be justified.

Biopsy-proven recurrence of unilateral IgG4-related orbital inflammation after 20 years.

A 38-year-old female patient presented with a painful swelling in the lateral part of the upper eyelid, a diffuse scleritis and slight hypoglobus of the right eye. An orbital biopsy showed a fibrotic idiopathic orbital inflammation (IOI) with, on immunohistochemical staining, an increased number of IgG4-positive plasma cells scored as >200 per high-power field, with IgG4/IgG ratio >0.50, indicating orbital IgG4 related autoimmune disease. On treatment with oral prednisone and azathioprine the symptoms resolved within 6 months. Twenty years prior, the patient had been diagnosed with an IOI of at the same side, for which at that time a biopsy had been taken similarly. Reclassification of the previous biopsy specimen with immunohistological staining also showed evidence of orbital IgG4 related disease. To our knowledge this is the first report of a biopsy-proven unilateral IgG4-related orbitopathy that recurred after 20 years.

PDGF enhances orbital fibroblast responses to TSHR stimulating autoantibodies in Graves' ophthalmopathy patients.

PURPOSE: Thyroid-stimulating hormone receptor (TSHR) stimulating autoantibodies are associated with Graves' ophthalmopathy (GO), the orbital manifestation of Graves' disease (GD). TSHR autoantibody levels and orbital TSHR expression levels correlate positively with GO disease activity. Platelet-derived growth factors (PDGF) are increased in GO and potently activate orbital fibroblast effector functions. We investigated the possible relationship between PDGF and TSHR expression on orbital fibroblasts and how that influences the immunopathological effects of TSHR autoantibodies on orbital fibroblast activity. METHODS: Orbital fibroblasts were stimulated with PDGF-AA, PDGF-AB, and PDGF-BB, and TSHR expression was determined by flow cytometry. Stimulatory effects of bovine TSH and GD immunoglobulins on orbital fibroblasts (with or without PDGF-BB preincubation) were determined by IL-6, IL-8, chemokine (C-C motif) ligand (CCL)-2, CCL5, CCL7, and hyaluronan ELISA. The TSHR blocking antibody K1-70 and the cAMP inhibitor H89 were used to determine involvement of TSHR signaling. RESULTS: PDGF-AB and PDGF-BB stimulation increased TSHR expression on orbital fibroblasts, whereas PDGF-AA did not. Furthermore, stimulation with bovine TSH and immunoglobulins from GD patients induced IL-6, IL-8, CCL2, and hyaluronan production by orbital fibroblasts, and PDGF-BB preincubation enhanced this response of orbital fibroblasts. Blocking studies with a TSHR blocking antibody and a cAMP inhibitor inhibited these effects, indicating the involvement of TSHR signaling and thus of TSHR stimulating autoantibodies herein. CONCLUSIONS: These findings indicate that PDGF-B containing PDGF isoforms amplify the immunopathological effects of TSHR-stimulating autoantibodies in GO patients by stimulating TSHR expression on orbital fibroblasts.

Orbit-infiltrating mast cells, monocytes, and macrophages produce PDGF isoforms that orchestrate orbital fibroblast activation in Graves' ophthalmopathy.

PURPOSE: Platelet-derived growth factors (PDGF) are regulators of fibroblast activity that may be involved in the pathophysiology of Graves' ophthalmopathy (GO). We unraveled the expression and origin of PDGF family members in GO orbital tissue and investigated the effect of PDGF isoforms on IL-6 and hyaluronan production and proliferation by orbital fibroblasts. METHODS: PDGF-A, PDGF-B, PDGF-C, PDGF-D, PDGF-Rα, and PDGF-Rß expression was determined by real-time quantitative PCR and PDGF-A and PDGF-B protein expression was determined by Western blot in orbital tissues. Orbital tissues were immunohistochemically stained for PDGF-A and PDGF-B expression, together with stainings for T cells, monocytes, B cells, macrophages, and mast cells. Effects of PDGF-AA, PDGF-AB, and PDGF-BB on orbital fibroblast proliferation and IL-6 and hyaluronan production were examined. Finally, effects of PDGF-BB- and PDGF-AA-neutralizing antibodies on IL-6 and hyaluronan production in GO whole orbital tissue cultures were tested. RESULTS: GO orbital tissue showed increased PDGF-A and PDGF-B mRNA and protein levels. Increased numbers of PDGF-A- and PDGF-B-positive monocytes, macrophages, and mast cells were present in GO orbital tissue. PDGF-BB stimulated proliferation and hyaluronan and IL-6 production by orbital fibroblasts the most, followed by PDGF-AB and PDGF-AA. Finally, in particular imatinib mesylate and PDGF-BB-neutralizing antibodies reduced IL-6 and hyaluronan production by whole orbital tissue cultures from GO patients. CONCLUSIONS: In GO, mast cells, monocytes, and macrophages may activate orbital fibroblasts via secretion of especially PDGF-AB and PDGF-BB. Preclinical studies with whole orbital tissue cultures show that blocking PDGF-B chain containing isoforms can be a promising treatment for GO.

[Orbital metastases of breast cancer. Radiologic features]. / Mammakarzinommetastasen der Orbita. Radiologische Eigenschaften.

BACKGROUND: We reviewed the radiologic features of 15 patients with orbital metastases originating from breast cancer. METHODS: This was a retrospective consecutive case series. Fifteen consecutive patients with orbital metastases originating from breast carcinoma were identified between March 1997 and September 2008. A retrospective chart review was carried out, and the radiologic findings were reviewed. RESULTS: The metastases were preseptal in 53%, intraconal in 60%, and both intraconal and extraconal in 33%. Lacrimal gland enlargement was noted in 33%, episcleral space involvement in 33%, bone involvement in 13%, and globe dystopia in 53%. The extraocular muscles were involved in 87%; in 60%, two or more muscles were involved. The medial and lateral rectus muscles were affected in 53% and 47%, respectively, and the inferior and superior rectus muscles in 33%. In 47% one or more radiologic features had not been noted by the radiologist, and in 20% the findings were misinterpreted as an"orbital pseudotumor." CONCLUSION: Orbital metastases originating from breast cancer may present heterogeneously. Orbital imaging most commonly shows unilateral and multifocal involvement of multiple extraocular muscles and intraconal and preseptal areas by an irregular lesion.

[The effect of specialised medical procedures on the hosptial standardised mortality ratio in cardiac centers]. / Hartcentra en het effect van bijzondere medische verrichtingen op het gestandaardiseerde ziekenhuissterftecijfer.

OBJECTIVE: To examine the impact of specialised medical procedures (SMPs) on the hospital standardized mortality ratio (HSMR) in Dutch cardiac centres. DESIGN: Retrospective, calculation of the HSMR. METHOD: Data from 2004 from the National Medical Registration (LMR) were used to calculate the HSMR in 12 cardiac centres and all other hospitals in the Netherlands. The HSMRwas then recalculated for the 12 cardiac centres excluding either percutaneous transluminal coronary angioplasty (PTCA) or open heart surgery or both to determine the impact of these SMPs on the HSMR. RESULTS: Exclusion of SMPs from the HSMR calculation changed the HSMR for individual cardiac centres, ranging from a 4.7% decrease to a 5.3% increase. Change in HSMR was related to the relative frequency of the two procedures at each cardiac centre. Mortality risk was lower than average for PTCA and higher than average for open heart surgery. PTCA accounted for 5.6%-20.2% of total admissions in the 12 cardiac centres. A relatively high proportion of PTCA procedures was associated with a lower HSMR, to a maximum decrease of nearly 7% in one cardiac centre. Open heart surgery accounted for 2.1%-12.6% of total admissions per cardiac centre. A relatively high proportion ofopen heart procedures was associated with an increased HSMR, to a maximum increase of nearly 8% in one cardiac centre. CONCLUSION: Specialised medical procedures for heart conditions influence the HSMR of cardiac centres. The increase or decrease in HSMR is related to the relative frequency of PTCA and open heart surgery. These results can be used to help interpret the differences in HSMR among cardiac centres and other hospitals.

[The practice guideline 'Problematic alcohol consumption' (second revision) from the Dutch College of General Practitioners; a response from the perspective of general practice]. / De standaard 'Problematisch alcoholgebruik' (tweede herziening) van het Nederlands Huisartsen Genootschap; reactie vanuit de huisartsgeneeskunde.

The recently revised version of the practice guideline 'Problematic alcohol consumption' from the Dutch College of General Practitioners offers realistic advice to general practitioners on how to manage problem drinkers. The number of patients with alcohol problems tends to increase among women of middle age. The proportion of patients that report an alcohol problem themselves is larger than is usually assumed. Questionnaires are oflimited value in the detection of an alcohol problem. The general practitioner should look at problem drinking as a chronic disease that demands structured disease management and monitoring. This perspective will lead to less frustration in handling both the problem and the patients.

Efficacy and side effects of 'swinging eyelid' orbital decompression in Graves' orbitopathy: a proposal for standardized evaluation of diplopia.

OBJECTIVES: To evaluate the efficacy and side effects of 'swinging eyelid' orbital decompression in patients with Graves' orbitopathy (GO). To calculate the incidence of postoperative new-onset diplopia (NOD) using a newly proposed scoring system for diplopia. METHODS: We reviewed the clinical data on proptosis, visual acuity, and diplopia in 104 consecutive patients (198 orbits) with GO, who underwent orbital decompression. A combined lateral canthal and inferior fornix incision ('swinging eyelid' approach) was used for removal of the medial wall, the orbital floor and, if indicated, the lateral wall. Indications for surgery were disfiguring/congestive GO (DGO) in 79 patients (149 orbits) and compressive optic neuropathy (CON) in 25 patients (49 orbits). Diplopia was scored according to four grades. In both groups, the incidence of new-onset (continuous) diplopia (NOD), deterioration of diplopia (DOD), and improvement of diplopia (IOD) were calculated, using strictly defined criteria. Our data on NOD were compared to those from other series, after recalculation according to our criteria. RESULTS: The mean proptosis reduction was 4.6 mm (range 0-9.5 mm) after three-wall decompression (95 patients, 180 orbits) vs 3.1 mm (range 0-7 mm) after two-wall decompression (nine patients, 18 orbits). The visual acuity improved in 98% of the patients with CON. In patients with DGO, NOD occurred in 14%. In patients with CON, NOD was not observed, but DOD occurred in 41%. Our data compare favourably to the reported incidence of NOD after either transantral or transnasal decompression. CONCLUSIONS: "Swinging eyelid' orbital decompression is efficacious for proptosis reduction as well as for optic nerve decompression. A scoring system for standardized evaluation of diplopia is proposed.

[Giant mucocele of all paranasal sinuses with massive bilateral globe displacement]. / Riesen-Mukozele der Nasennebenhöhlen mit bilateraler Bulbusverlagerung.

Although of benign nature and slowly progressive, paranasal sinus mucoceles may, depending on their localization, cause a multitude of ophthalmological symptoms due to compression and displacement of adjacent tissue. Here we report the unusual case of a patient suffering from a progressively growing giant mucocele that developed years after ENT surgery and that was neglected for almost 2 decades despite massive symptoms. This case report demonstrates the importance of including mucoceles of the paranasal sinuses into the differential diagnosis of unilateral or bilateral proptosis.

[Adenotonsillectomy in children only under exceptional circumstances]. / Adenotonsillectomie bij kinderen: neen, tenzij.

More and more evidence is becoming available that throws doubt on the value of adenotonsillectomy in children with frequent throat infections or hypertrophic tonsils and adenoids. Tonsillectomy and adenoidectomy have a limited range of indications. Objective symptoms such as the size of the tonsils and subjective symptoms of obstruction and sore throat are not always related to each other. Children with only moderate symptoms should not be operated on.

The effect of etanercept on Graves' ophthalmopathy: a pilot study.

PURPOSE: To assess the effect of etanercept, an antitumour necrosis factor (anti-TNF) drug, on clinical signs in Graves' ophthalmopathy (GO). METHODS: A total of 10 consecutive patients (seven female, three male) with recent-onset, active, mildly-to-moderately severe GO were treated with subcutaneous injections of 25 mg etanercept (Enbrel) twice weekly during 12 weeks. The average age was 50 years (range: 39-59 years). The average duration of GO was 4 months (range: 2-6 months). All patients were at least 2 months euthyroid with medication. The mean pretreatment clinical activity score (CAS) was 4 (range: 3-6). RESULTS: The mean CAS prior to treatment was 4, at 6 weeks 2.6, and at 12 weeks 1.6. The mean ophthalmopathy index (OI) prior to treatment was 5.8, at 6 weeks 4.8, and at 12 weeks 4.4. Thus, after 12 weeks of treatment the mean CAS had decreased by 2.4+/-1.3 (60%), and the mean OI had decreased by 1.4+/-1.2 (24%). The main decrease of the CAS and OI was noted at 6 weeks of treatment. The difference was particularly evident on soft-tissue changes, including periocular chemosis and redness. The mean exophthalmometry values did not change. In all, 60% percent of patients reported moderate to marked improvement. In three patients, the GO flared up again after cessation of treatment. There were no serious adverse events or side effects during a mean follow-up time of 18 months. CONCLUSIONS: This study strongly suggests that etanercept may suppress the clinical signs in GO, but randomized controlled trials are needed to further evaluate the effect of anti-TNF treatment and to compare its side-effects with those of corticosteroids.

[Relationship between te general practice guidelines for the diagnosis of hypertension and the indication for treatment and practice in the Nijmegen region, the Netherlands, 1983-2001]. / Samenhang tussen de huisartsrichtlijnen voor diagnostiek van hypertensie en indicatie tot behandeling en de praktijk in de regio Nijmegen, 1983-2001.

OBJECTIVE: To determine whether patients with hypertension in general practice are diagnosed and treated according to the criteria of the Dutch College of General Practitioners guidelines. DESIGN: Retrospective, descriptive. METHOD: Using data from 9 general practices belonging to the general practice research network of the Academic Medical Centre St Radboud, Nijmegen, the Netherlands, all intake data of newly diagnosed hypertensive patients were collected. Three periods (1983-1991, 1992-1996 and 1997-2001) were studied and compared to the 1991 and 1997 versions of the guidelines. RESULTS: During the study period, 1959 patients with hypertension were registered. In 4% of the men and 3% of the women the hypertension criteria of the time were not met. These figures decreased during the course of the research period. Mean blood pressure at diagnosis was above 160/100 mmHg, even in patients with diabetes. The additional risk factors were recorded increasingly frequently (cholesterol level, smoking behaviour, body-mass index). In 1991, 63% were treated with medication (the other 37% only received lifestyle advice). During the last period, 86% received medication, while the indication to prescribe medication according to the guidelines increased from 40% to 81%. The increase may be ascribed to the new guideline recommendation of one risk factor as an indication to treat patients with mild hypertension instead of two. CONCLUSION: Almost all patients in whom the participating general practitioners diagnosed hypertension fulfilled the criteria. The difference in threshold values for diagnostic measurements and medicinal treatment means that people with mild hypertension are not always registered and consequently risk being forgotten by their general practitioner.

[The Dutch College of General Practitioners' practice guideline 'Diagnosis of breast cancer': reaction from the field of general practice]. / De standaard 'Diagnostiek van mammacarcinoom' van het Nederlands Huisartsen Genootschap; reactie vanuit de huisartsgeneeskunde.

In the revised practice guideline on the diagnosis of breast cancer, the general practitioner has an important role when, during screening, a woman is found to have an abnormality, before, during and after treatment. Breast clinics allow the situation to be dealt with rapidly, but patients also need time to cope with it all. In young women with breast complaints, but without palpable abnormalities, the practice guideline recommends mammography to be on the safe side. However, in a group with a low prevalence, this carries primarily disadvantages; the patient does need to be properly followed. The policy for patients with a positive family history of breast cancer has been clearly worded.

[The Dutch College of General Practitioners practice guideline 'The menopause'; reaction of the field of general practice]. / De standaard 'De overgang' van het Nederlands Huisartsen Genootschap; reactie vanuit de huisartsgeneeskunde.

The Dutch College of General Practitioners' practice guideline on the menopause will not be any major cause for discussion. The hot issue of giving oestrogens to peri- and postmenopausal women to prevent osteoporosis or cardiovascular disease was already covered in the practice guideline on osteoporosis. This guideline on the menopause shows that there is no consensus on when it is safe to stop contraception. The advice to use supplementary contraception, such as condoms, until 1 year after the last menstruation will not be met with a high rate of compliance. If oestrogen therapy is necessary in women with serious vasomotor symptoms who still have their uterus, calendar packets containing 14-16 oestrogen-only pills and 12-14 oestrogen/progesterone combination pills can be used. Administration of transdermal oestrogens has no added value and is more expensive. Tibolone is even more expensive and has more side effects. Clonidine is less effective but can be an alternative for women who choose not to take hormones or in whom oestrogens are contraindicated.

Cardiovascular risk factors and disease in general practice: results of the Nijmegen Cohort Study.

The relationship between risk factors and cardiovascular disease (CVD) was determined using data from the Nijmegen Cohort study, an 18-year prospective study. In 1977, cardiovascular risk factors were measured in 7092 Caucasian males and females from six general practices: age, smoking, serum cholesterol, blood pressure, body mass index and a family history of CVD were related to subsequent CVD mortality and morbidity. Most patients had more than one risk factor in particular among men. A significant relationship between risk factors and CVD was demonstrated. In men, a relative risk (RR) of 1.8 was found for both high blood pressure and smokers. A positive family history yielded a RR of 1.8. The risk increased gradually with the number of risk factors; 38% of the group with all risk factors suffered a CVD within 18 years. In women, comparable RRs were found but the low absolute risk of CVD should indicate against the treatment of cardiovascular risk factors.

Amniotic membrane transplantation in the management of conjunctival malignant melanoma and primary acquired melanosis with atypia.

AIM: To evaluate the efficacy of amniotic membrane transplantation (AMT) for the management of conjunctival malignant melanoma and primary acquired melanosis (PAM) with atypia. METHODS: Four consecutive patients with histologically proved invasive, primary conjunctival malignant melanoma were treated with wide surgical excision and AMT. Amniotic membrane grafts were harvested and processed under sterile conditions according to a standard protocol. The grafts were sutured to the margins of the surface defect. In one case, AMT was combined with a corneoscleral graft. RESULTS: A satisfactory result and rapid postoperative recovery with few, transient side effects was noted in three patients with limbal/epibulbar melanomas. In another patient with an extensive lesion, involving the epibulbar, forniceal, and palpebral conjunctiva, AMT following wide excision was complicated by symblepharon formation and restricted ocular motility. Monitoring of local recurrence was facilitated by the transparency of the thin graft in all cases. The postoperative follow up time varied between several months and 3 years. In one case, local recurrence of PAM was observed and treated using topical mitomycin. CONCLUSIONS: AMT is a useful technique for the reconstruction of both small and large surface defects that result from the surgical excision of conjunctival malignant melanoma and PAM. This method facilitates wide conjunctivectomy, although its role in repairing larger defects involving the fornix or palpebral conjunctiva still needs to be established. The transparency of amniotic membrane allows for monitoring of tumour recurrence, which is-together with superior cosmesis-an advantage over thicker (for example, buccal) mucous membrane grafts.

Blood pressure and cardiovascular morbidity and mortality in a Dutch population: the Nijmegen cohort study.

BACKGROUND: The objective was to determine the influence of systolic blood pressure and diastolic blood pressure on the development of coronary heart disease over an 18-year period in a Dutch general practice population. METHODS: The Nijmegen Cohort Study is a prospective cohort study with an 18-year follow-up. In 1977 systolic blood pressure, diastolic blood pressure, and other cardiovascular risk factors were measured in 7,092 Caucasians, men and women. The screening took place in six general practices, participating in a university registration network. Cardiovascular disease and all mortality was registrated during the 1977-1995 period. A Cox proportional hazard model was performed separately for men and women with the first onset of a coronary heart disease as the outcome variable. Age, smoking, serum cholesterol, blood pressure, and socioeconomic class were included as independent variables. RESULTS: During the 18-year follow-up period, 205 men and 63 women suffered a nonfatal myocardial infarction. During this time, 205 deaths were identified, of which 54 were cardiovascular. Of all deaths, 139 were noncardiovascular, of which 10% were due to accident or suicide, while in 12 participants the cause of death was uncertain. The analysis indicated that both the systolic and the diastolic blood pressure were independently associated with the likelihood for developing coronary heart disease, as were the other risk factors. For coronary heart disease, the significant risk ratios for the systolic blood pressure were 1.6 for men and 2.1 for women. For the diastolic blood pressure a risk ratio was found of 1.4 for men and 2.0 for women. CONCLUSION: A significant relation between blood pressure and coronary heart disease was demonstrated. As mean blood pressures, cholesterol levels, smoking habits, and socioeconomic class in this cohort did not differ from other figures in The Netherlands, extrapolation of the results to the Dutch population is possible.