Baseline serum levels of IgA anti-cyclic citrullinated protein antibodies in early rheumatoid arthritis predict radiographic progression after 11 years of treatment: a secondary analysis of the CIMESTRA study.

OBJECTIVE: Smoking and periodontitis are risk factors for developing rheumatoid arthritis (RA), suggesting a break of tolerance on mucosal surfaces. Immunoglobulin A (IgA) antibodies are part of the mucosal immune system. The dominant autoantibodies in RA are anti-cyclic citrullinated protein antibodies (ACPAs), and IgG and IgA subclasses exist simultaneously. This study aimed to investigate the association of ACPA IgA subtypes with disease activity and long-term radiographic outcomes in RA, compared with ACPA IgG. METHOD: Total ACPA IgG, IgA, IgA1, and IgA2 were quantified in serum from patients with early RA (n = 97). Patient characteristics, IgM rheumatoid factor (IgM-RF) status, clinical and biochemical disease activity scores, and radiographic status evaluated by total Sharp score (TSS), were assessed at baseline and after 2 and 11 years of treatment. RESULTS: All patients with ACPA IgA also had ACPA IgG. ACPA IgA positivity was associated with IgM-RF and male gender. Both ACPA IgA and IgG levels at baseline were weakly associated with disease activity markers. Baseline ACPA IgA and IgG did not show a linear correlation with radiographic status after 10 years, but could predict radiographic progression (ΔTSS ≥ 5 from 0 to 11 years), with positive likelihood ratios of 3.7 and 4.0, respectively. CONCLUSION: ACPA IgA and IgG were weakly associated with disease activity in early RA. RA patients with a ΔTSS ≥ 5 after 11 years of treatment had higher ACPA IgG and ACPA IgA levels at baseline; however, none of the ACPA subtypes was superior in predicting long-term radiographic progression.

Multicentre study of the risk of invasive cancer and use of sentinel node biopsy in women with a preoperative diagnosis of ductal carcinoma in situ.

BACKGROUND: Ductal carcinoma in situ (DCIS) in the breast that is diagnosed by biopsy implies a risk of upstaging to invasive carcinoma (IC) on final pathology. These patients require a sentinel lymph node biopsy (SLNB) for axillary staging. A two-stage procedure is not always feasible and precise selection of patients who should be offered SLNB is crucial. The aims were: to determine the rate of upstaging, and use of redundant and required SLNB in women with a preoperative diagnosis of DCIS; and to identify patient and tumour characteristics that increase the risk of upstaging. METHODS: Patients with DCIS treated between 2008 and 2016 were identified using Orbit operation planning system software, and those suitable for the study were selected based on review of the medical records. Upstaging rates and proportions of redundant and required SLNBs were calculated. Associations between clinicopathological characteristics and upstaging were analysed using univariable and multivariable logistic regression analyses. RESULTS: Of 1368 patients initially identified, 975 women with a preoperative diagnosis of DCIS were included in the study. Tumours in 246 of these patients (25·2 per cent) were upstaged to IC. Redundant SLNB was performed in 392 of 975 women (40·2 per cent). Forty-four patients (4·5 per cent) with a final diagnosis of IC were not offered SLNB and thus potentially undertreated. In adjusted analysis, DCIS size, palpability and mass formation identified by breast imaging were associated with increased risk of upstaging. The Van Nuys classification was not associated with upstaging. CONCLUSION: Most patients with IC on final pathology underwent SLNB, but a considerable number of patients with DCIS had a redundant SLNB. Lesion size, palpability and mass formation, but not Van Nuys classification group, are suggested risk factors for upstaging.

ANTECEDENTES: El carcinoma ductal in situ (ductal carcinoma in situ, DCIS) de mama que se diagnostica mediante biopsia implica un riesgo de infraestadiaje de un carcinoma invasivo (invasive carcinoma, IC) en la anatomía patológica final. Estas pacientes requieren una biopsia del ganglio linfático centinela (sentinel lymph node biopsy, SLNB) para la estadificación axilar. Dado que un procedimiento en dos etapas no siempre es factible, la selección precisa de pacientes a las que se debe ofrecer SLNB es crucial. El objetivo del estudio era determinar la tasa de infraestadiaje inicial y el uso repetido/requerido de SLNB en mujeres con un diagnóstico preoperatorio de CDIS. Además, se identificarán las características del paciente y del tumor que aumentan el riesgo de necesidad de re-estadificación. MÉTODOS: Un total de 1.368 mujeres con DCIS tratadas entre 2008-2016 fueron identificadas utilizando el programa informático de la planificación de las intervenciones hospitalarias. Después de la revisión de los registros médicos, se incluyeron 975 pacientes en la cohorte del estudio. Se calcularon las tasas de infraestadiaje y la proporción del uso repetido/requerido de SLNB. Las asociaciones entre las características clinicopatológicas y la necesidad de re-estadificación se analizaron mediante análisis de regresión logística univariable y multivariable. RESULTADOS: De 975 pacientes diagnosticados inicialmente de DCIS, 246 (25,2%) fueron re-estadiados a IC. Se realizó SLNB repetidas en 392 (40,2%) de estos pacientes. En 44 pacientes (4,5%) con un diagnóstico final de IC no se les ofreció la SLNB y, por lo tanto, pudieron estar potencialmente infratratados. En el análisis ajustado, el tamaño del DCIS, la palpabilidad y la presencia de una masa en las imágenes radiológicas de la mama se asociaron con un mayor riesgo de necesidad de re-estadificación por infraestadiaje inicial. La clasificación de Van Nuys no se asoció con la re-estadificación. CONCLUSIÓN: La mayoría de pacientes con IC en la patología final se sometieron a SLNB, sin embargo, un número considerable de pacientes con DCIS se sometieron a SLNB repetidas. El tamaño de la lesión, la palpabilidad y la presencia de masa, aunque no el grupo de clasificación de Van Nuys, se consideran factores de riesgo relacionados con infraestadiaje inicial y necesidad de re-estadificación final.

A prospective cohort study of 122 adult patients presenting to an otolaryngologist's office with globus pharyngeus.

OBJECTIVES: To investigate the epidemiology of globus pharyngeus in adult patients presenting to the otolaryngologist's office. Also, the predictors of persisting symptoms, prevalence of anxiety and the effect of clinical assessment were analysed. DESIGN: This was a prospective cohort study. Follow-up was carried out using a postal questionnaire. SETTING: One otolaryngologists' office comprising three medical doctors. PARTICIPANTS: A total of 122 consecutive globus patients presenting to one otolaryngology office in a 1-year period. MAIN OUTCOME MEASURES: Globus incidence, gender and age distribution, predictors of persisting symptoms and the patient's health-related concerns. RESULTS: 3.8% of first-time visits were regarding globus. The mean age was 48 years [range 20-88 years], and a female predominance was found (ratio 1.49). Eighty-four per cent experienced anxiety, mainly due to fear of cancer. The most common pathological findings were reflux (15.6%) and post-infectious inflammation (10.6%). 21.4% of questionnaire responders reported full remission of their symptoms. Three predictors regarding symptom persistence were identified: male gender (OR 1.52), smoking (OR 3.4) and difficulties in breathing (OR 8.7). Patients with concomitant foreign body sensation were less likely to have persisting symptoms (OR 0.42). No cases of malignant disease were encountered. 94.7% was reassured by the office visit. CONCLUSION: The incidence of globus is 3.8% in the otolaryngologist's office. Female gender and concomitant foreign body sensation were predictive for presenting to the clinic even if symptom remission had occurred. Male gender, smoking and self-perceived breathing difficulties were predictive for persisting symptoms. Globus is an anxiety-causing symptom, but reassurance is provided by clinical examination by the otolaryngologist.

Presence and localization of bacteria in the bovine endometrium postpartum using fluorescence in situ hybridization.

The aim of this study was to investigate bacterial invasiveness of the bovine endometrium during the postpartum period. Fluorescence in situ hybridization was applied to endometrial biopsies using probes for Fusobacterium necrophorum, Porphyromonas levii, Trueperella pyogenes, Escherichia coli and a probe for bacteria in general (the overall domain Bacteria) to determine their tissue localization. Holstein cows were sampled at three time points postpartum (T1: 4-12 days postpartum, T2: 24-32 days postpartum and T3: 46-54 days postpartum). At T1, cows were clinically scored as having a uterine infection based on presence of a brownish, fetid vaginal discharge or as normal if having normal lochia. An endometrial biopsy was taken from all cows at T1 (n = 57). Endometrial biopsies were taken from the same cows at T2 and T3 if allowed by the size of the cervical canal and if the cow had not been inseminated. Fifty and 39 biopsies were obtained at T2 and T3, respectively. The biopsies were evaluated for inflammation and for presence and localization of bacteria. When analyzed by the probe for the entire domain Bacteria, bacteria were found in most biopsies irrespectively of time (T1: 79.0%, T2: 82.0%, T3: 89.7%). Fusobacterium necrophorum and Porphyromonas levii were often present in the endometrium at T1 (61.1% and 47.8%, respectively), but the prevalence decreased significantly over time. Trueperella pyogenes and Escherichia coli were less prevalent at T1 (8.8% and 10.5%, respectively) and their prevalence also decreased significantly over time. Fusobacterium necrophorum and Porphyromonas levii were often co-localized intraepithelially or in the lamina propria. Trueperella pyogenes and Escherichia coli were located only on the endometrial surface. Due to the high prevalence of tissue invasiveness, these findings emphasize the importance of Fusobacterium necrophorum and Porphyromonas levii in postpartum uterine disease of cattle and indicate that tissue invasiveness is an important aspect of the pathogenesis.

A Pharmacokinetic and Safety Study of Trebananib, an Fc-Fusion Peptibody, in Patients With Advanced Solid Tumors and Varying Degrees of Renal Dysfunction.

Clearance of trebananib (AMG 386), a 64-kD antiangiogenic peptibody, has been associated with estimated glomerular filtration rate (eGFR). We prospectively evaluated trebananib pharmacokinetics and safety/tolerability in advanced solid tumor patients with varying degrees of renal function. Patients were assigned to normal renal function, mild, moderate, or severe renal dysfunction cohorts based on eGFR, received trebananib 15 mg/kg i.v. weekly, and underwent week 1 and week 5 pharmacokinetic and weekly safety assessments. For 28 patients, trebananib clearance decreased from normal renal function (1.52 mL/hr/kg), to mild (1.20 mL/hr/kg), moderate (0.79 mL/hr/kg), and severe (0.53 mL/hr/kg) renal dysfunction (P ≤ 0.001). Treatment-related adverse events showed no association with clearance. Trebananib clearance was proportional to eGFR and unrelated to pretreatment protein excretion. These data confirm a role for renal clearance of a recombinant peptibody with molecular weight <69 kD and support a longer dosing interval for patients with severe renal dysfunction.

Antigen-induced cytokine and chemokine release test for tuberculosis infection using adsorption of stimulated whole blood on filter paper and multiplex analysis.

BACKGROUND: In vitro stimulation of whole blood or isolated blood cells with specific antigens is used for several purposes. Immediately following incubation with antigens, samples have to be centrifuged to stop the reactions by remaining cells and the supernatant refrigerated or analysed directly to preserve the analytes of interest, which makes samples difficult to prepare outside laboratories. We have tested whether spotting whole blood on filter paper after activation can be used in one of the tests for Mycobacterium tuberculosis infection (MTI), the QuantiFERON®-TB Gold In Tube test (QFT), where the spotting technique can make it suitable for use in locations without facilities like a centrifuge and a refrigerator. MATERIALS AND METHODS: Samples from 22 individuals undergoing screening for MTI and 10 healthy controls were incubated, centrifuged and IFN-γ measured by Enzyme-linked immunosorbent assay (ELISA), as described in the kit insert. In parallel, activated blood was spotted on filter paper (Schleicher & Schuell) and dried. The dried blood spot samples were analysed for 21 inflammatory markers with an in-house assay based on Luminex technology. RESULTS: Our multiplex measurements of inflammatory markers in samples from suspected MTI patients confirmed the IFN-γ findings in the QFT. IL-2, GM-CSF, IL-5, and IL-1ß were also found as useful markers for MTI. We were not able to distinguish between active tuberculosis and latent MTI. CONCLUSION: Applying blood on filter paper after incubation makes in vitro stimulation tests feasible in locations where heat and electricity is unavailable.

Combined IL-12 receptor and IgA deficiency in an adult man intestinally infested by an unknown, non-cultivable mycobacterium.

Interleukin-12 receptor deficiency is a well-described cause of human susceptibility to infection with low-virulent mycobacteria and Salmonella species. We identified a male patient presenting in his late forties with severe gastroenteropathy because of outbred infestation by a previously unknown mycobacterium. In addition to selective IgA deficiency, the patient was found to carry a not previously described R283X homozygous mutation in his IL12RΒ1 gene. Two of his sisters, a brother, and his four children were healthy, heterozygous carriers of the mutation. In this patient, the combination of two deficiencies could promote illness. Even though the IgA deficiency in itself does not predispose to mycobacterial disease, the lack of secreted IgA may have disturbed the intestinal homoeostasis and increased the susceptibility to the low-virulent mycobacterium that the patient was not able to clear because of his IL12R deficiency. Antimycobacterial chemotherapy and interferon-γ treatment for 2 years significantly improved his condition. This is the first description of IL12RΒ1 deficiency combined with another immunodeficiency, and we suggest that combinatory defects may circumvent the otherwise low penetrance of IL12RB1 deficiency.

A prospective study of medically treated acute type B aortic dissection.

OBJECTIVE: To study prospectively aneurysm formation, need of surgery, incidence of rupture and mortality in patients with conservatively treated acute type B aortic dissection. METHODS: All patients referred to us with acute type B dissection between January 1990 and December 2001 were candidates for this prospective treatment and follow-up study. Patients deemed not to be in need of acute surgical repair were included after aggressive antihypertensive treatment. The follow-up protocol included close blood pressure control, clinic visits with physical examination, chest x-ray and spiral CT or MRI at 3 and 6 months and annually thereafter. RESULTS: Sixty-six patients were followed for a mean of 79 months (range 22-179). The actuarial survival rate was 82% at 5 years and 69% at 10 years. Eighty-five percent remained free from dissection-related death at 5 years and 82% at 10 years. Ten patients (15%) developed aneurysm (>6 cm) of the dissected aorta. Three of these 10 patients died from aortic rupture and 2 underwent elective surgical repair. Of the 56 patients without aneurysm, one died from rupture and one died suddenly for causes unknown. One patient was treated with endovascular stent-graft. Five patients sustained a new type A aortic dissection which in all but one were fatal. In 26 patients the initial dissection was categorized as intramural hematoma. Twelve of these patients had, in addition to the hematoma, areas with localized dissection/ulcer-like projection. The latter was found to be a predictor of aortic event (dissection-related death, rupture, new type A aortic dissection, aneurysm formation) during follow-up, as was an initial diameter of >4.0 cm at first CT-scan during the acute event. CONCLUSIONS: Conservatively treated acute type B dissection has a low incidence of aneurysm formation and rupture during the chronic phase. These results must be matched or improved upon before endovascular stent-grafting or early aortic surgical repair can be regarded as the primary treatment of choice.

Transesophageal endoscopic ultrasound/fine-needle aspiration diagnosis of a malignant adrenal gland in a patient with non-small cell lung cancer and a negative CT scan.

Adrenal metastasis is only seen on CT scan is less than 5% of patients with otherwise resectable NSCLS, but this diagnosis has a major impact on treatment and prognosis. We present a case of a patient with NSCLC and an adrenal metastasis, which was diagnosed by EUS/FNA of an enlarged adrenal gland, who had false-negative CT scan for adrenal metastasis. PET was not performed. Prospective studies are needed to assess the incremental yield of EUS/FNA over upper abdominal CT scan and PET for detecting left adrenal metastasis in patients with suspected or proven otherwise respectable NSCLC.

Interstitial lung disease, a common manifestation of newly diagnosed polymyositis and dermatomyositis.

OBJECTIVES: To estimate the prevalence and predictors of interstitial lung disease in newly diagnosed polymyositis and dermatomyositis. METHODS: A prospective study in which consecutive patients with newly diagnosed poly- and dermatomyositis, regardless of clinical symptoms of pulmonary disease, were investigated with chest x ray, high resolution computed tomography (HRCT), pulmonary function tests, and biochemical and autoantibody analysis. Patients with inclusion body myositis, malignancy, other defined inflammatory connective tissue diseases (CTDs), or antibody profile indicating other CTDs were excluded. RESULTS: Between March 1998 and September 2000, 26 new cases of poly- or dermatomyositis were diagnosed; 17 of those patients were included in the study. Interstitial lung disease (ILD), defined as radiological signs on chest x ray examination/HRCT or restrictive ventilatory defect, were found in 11 (65%) patients and were more common in men than in women. Arthritis and occurrence of anti-Jo-1 antibodies were found more often in patients with ILD than in those without. There was no statistically significant association between respiratory symptoms, other serological or laboratory variables and ILD. CONCLUSIONS: ILD is a common early manifestation in patients with poly- and dermatomyositis and is not always related to clinical symptoms. Chest x ray examination, HRCT, pulmonary function tests, and analysis of anti-Jo-1 antibodies should be included in the initial investigation of patients with myositis regardless of respiratory symptoms.

Lung perfusion scintigraphy prior to lung volume reduction surgery.

PURPOSE: The aim of this study was to evaluate whether lung perfusion scintigraphy (LPS) contributes to the preoperative classification of emphysema heterogeneity in patients undergoing LVRS (lung volume reduction surgery) compared to classification based only on computed tomography (CT). MATERIAL AND METHODS: Forty-five potential candidates for LVRS were examined with CT and LPS. The distribution of emphysema within the lungs was visually classified into three categories: markedly heterogeneous, intermediately heterogeneous, or homogeneous. The results of the two imaging techniques were compared to an objective, CT-based computerized classification of heterogeneity. RESULTS: Visual evaluation of all 90 lungs resulted in 50 correct classifications based on CT, in 40 based on LPS and in 68 correct classifications based on the combination of CT and LPS. The combination was superior to CT alone (p<0.01) in classification of emphysema heterogeneity. There was no significant difference between the evaluations based on either CT or LPS. CONCLUSION: The combined information from CT and LPS are superior in assessing emphysema heterogeneity prior to LVRS.

Toxicity testing and chemical analyses of recycled fibre-based paper for food contact.

Food-contact materials, including paper, have to comply with a basic set of criteria concerning safety. This means that paper for food contact should not give rise to migration of components, which can endanger human health. The objectives of this pilot study were, first, to compare paper of different qualities as food-contact materials and to perform a preliminary evaluation of their suitability, from a safety point of view, and, second, to evaluate the use of different in vitro toxicity tests for screening of paper and board. Paper produced from three different categories of recycled fibres (B-D) and a raw material produced from virgin fibres (A) were obtained from industry, and extracts were examined by chemical analyses and diverse in vitro toxicity test systems. The products tested were either based on different raw materials or different treatments were applied. Paper category B was made from 40% virgin fibres, 40% unprinted cuttings from newspapers, and 20% de-inked newspapers and magazines. Paper categories C and D were based on newspapers and magazines. However, paper D was de-inked, whereas C was not. To identify constituents of the papers with a potential to migrate into foodstuff, samples of the paper products were extracted with either 99% ethanol or water. Potential migrants in the extracts were identified and semiquantified by GC-IR-MS or GC-HRMS. In parallel to the chemical analyses, a battery of four different in vitro toxicity tests with different endpoints were applied to the same extracts. (1) a cytotoxicity test using normal human skin fibroblasts. The test was based on measurements of the reduction of resazurin to resorufin by cellular redox processes and used as a screening test for acute or general toxicity; (2) a Salmonella/microsome assay (Ames test) as a screening test for mutagenic and potentially carcinogenic compounds; (3) a recombinant yeast cell bioassay as a screening test for compounds with oestrogenic activity; (4) an aryl hydrocarbon (Ah)-receptor assay (CALUX assay) as a screening test for compounds with dioxin-like activity. In addition, the papers were testedfor microbial content and, in general, the microbiological load was quite low. The following microorganisms were counted and identified on both surface and homogenized pulp samples: the total number of aerobic bacteria, the number of aerobic and anaerobic spore formers, the number of Bacillus cereus/thuringiensis, and the number of yeast and moulds. The chemical analyses showed a significantly higher amount and different composition pattern of chemicals extracted with ethanol compared with water. Analyses of the ethanol extracts showed a distinctly smaller number and lower concentrations of chemicals in extracts prepared from sample A compared with extracts of samples B-D. The compounds identified in B-D were similar, but the amounts were lower in B compared with C and D. In accordance with the chemical analyses, the water extracts were less cytotoxic than the ethanol extracts. The extract prepared from virgin fibres was less cytotoxic than the extracts prepared from paper made from recycled fibres, and extracts prepared from C was the most cytotoxic. None of the extracts showed mutagenic activity. No conclusion about the oestrogenic activity could be made, because all extracts were cytotoxic to the test organism (yeast cells). Ethanol extracts of A and B showed a negligible positive response in the Ah-receptor assay at the highest nontoxic concentration, whereas C and D showed a more pronounced effect with C being the most potent. A comparable weak effect of water extracts of samples B-D was observed, too. However, the active compound(s) was not identified by chemical analyses.

Visual grading of emphysema severity in candidates for lung volume reduction surgery. Comparison between HRCT, spiral CT and "density-masked" images.

PURPOSE: To investigate which of three types of CT imaging yielded the best results in estimating the degree of emphysema in patients undergoing evaluation for lung volume reduction surgery (LVRS), whether there was any difference in this regard between the cranial and caudal part of the lung, and whether the degree of emphysema had an impact on the estimation. MATERIAL AND METHODS: Four radiologists visually classified different degrees of emphysema on three different types of CT images into four groups. The degree of emphysema was calculated by a computer. The three types of images were as follows: HRCT images (2-mm slice thickness); spiral CT images (10-mm slice thickness); and density-masked images (spiral CT images printed with pixels below -960 HU, depicted in white). RESULTS: The conventionally presented images from HRCT and spiral CT yielded the same results (60% respective 62% correct classifications) in assessing the degree of emphysema irrespective of localisation. Significantly improved results were obtained when the spiral CT images were presented as density-masked images (74%). CONCLUSION: There was no difference between HRCT and spiral CT in assessing the degree of emphysema in candidates for LVRS. Improvement can be achieved by the use of density-masked images.

Visual classification of emphysema heterogeneity compared with objective measurements: HRCT vs spiral CT in candidates for lung volume reduction surgery.

The aim of this study was to investigate whether spiral CT is superior to high-resolution computed tomography (HRCT) in evaluating the radiological morphology of emphysema, and whether the combination of both CT techniques improves the evaluation in patients undergoing lung volume reduction surgery (LVRS). The material consisted of HRCT (with 2-mm slice thickness) and spiral CT (with 10-mm slice thickness) of 94 candidates for LVRS. Selected image pairs from these examinations were evaluated. Each image pair consisted of one image from the cranial part of the lung and one image from the caudal part. The degree of emphysema in the two images was calculated by computer. The difference between the images determined the degree of heterogeneity. Five classes of heterogeneity were defined. The study was performed by visual classification of 95 image pairs (spiral CT) and 95 image pairs (HRCT) into one of five different classes of emphysema heterogeneity. This visual classification was compared with the computer-based classification. Spiral CT was superior to HRCT with 47% correct classifications of emphysema heterogeneity compared with 40% for HRCT-based classification ( p<0.05). The combination of the techniques did not improve the evaluation (42%). Spiral CT is superior to HRCT in determining heterogeneity of emphysema visually, and should be included in the pre-operative CT evaluation of LVRS candidates.

Thin-section CT vs spiral CT in candidates for lung volume reduction surgery: a comparison based on radiologists' subjective preferences.

The aim of this study was to investigate whether high-resolution (HRCT) or spiral CT was preferred in evaluating severe emphysema in patients undergoing lung volume reduction surgery (LVRS), whether there is any difference in this regard between the cranial and caudal part of the lung, and whether the degree of emphysema has an impact on the radiologists' preference. The study was performed by letting four radiologists compare images obtained with the two techniques (film pairs) and decide which technique they preferred or if the techniques were considered as equal in evaluating emphysema. In evaluation of 188 film pairs, the HRCT images were preferred in 56 %, spiral CT in 19 % and the techniques considered as equal in 25 %. Spiral CT images were preferred more often in the caudal part of the lung and in more advanced emphysema compared with the HRCT images. The study confirms our clinical assumption that use of both CT techniques are valuable in evaluating advanced emphysema and there may be technical as well as histopathological reasons for this.

African elephant sesquiterpenes.

GC-MS analysis of extracts from temporal gland secretions of an African elephant has revealed the presence of several farnesol-related sesquiterpenes. Among these are (E)-2, 3-dihydrofarnesol (3), a bumblebee pheromone not seen before in mammals, and a rare component of a Greek tobacco, drimane-8alpha, 11-diol (4), never observed before in an animal.

[A new MR-(and CT-) compatible bone biopsy system: first clinical results]. / Neues MR-(und CT-)kompatibles Knochenbiopsiesystem: Erste klinische Ergebnisse.

PURPOSE: To describe the development and clinical evaluation of a new, hand-powered or alternatively motor-driven, MRI and CT compatible percutaneous bone biopsy system. MATERIALS AND METHODS: A new coaxial drill system (Cook Europe A/S) was designed for percutaneous, MR-guided bone biopsies and powered either by hand or an optional motor (10-250 rotations/minute using 6 bar [88.2 PSI] compressed air). The system has been used in 23 patients. Fourteen procedures were performed in a 1.5 T MR scanner (Philips-Gyroscan ACS-NT) which has an attached C-arm (Philips-BV 212-Angio) in case fluoroscopy is required, and 9 procedures in a CT scanner (Siemens-Somatom Plus). RESULTS: Driven by hand or by the pneumatic motor unit, the system achieved safe and accurate MR-guided access to all of the lesions and was even able to penetrate osteosclerotic lesions. MR- or CT-guided percutaneous biopsy yielded a correct diagnosis in all but 5 cases. No procedural complications occurred. CONCLUSION: MR-guided percutaneous bone biopsy performed with the new coaxial drill system was found to be safe and reliable, and suitable for obtaining histological specimens from skeletal lesions even when covered with thick cortical or sclerotic bone.

Selective effects of somatostatin analogs on human drug-metabolizing enzymes.

Pharmacologic or surgical manipulation with growth hormone secretion or with the physiologic release of somatostatin and growth hormone-releasing hormone affects some rat liver enzymes, especially the sex-differentiated ones. We investigated the effects of two somatostatin analogs on several enzyme functions in six patients with carcinoid syndrome, using codeine as a probe drug. Codeine was given intravenously and its N- and O-demethylation, as well as 6-glucuronidation catalyzed by CYP3A, CYP2D6, and uridine diphosphate-glucuronosyltransferase, respectively, were studied before and during treatment with somatostatins. After 3 days of treatment with somatostatins the partial metabolic clearance of codeine by N-demethylation decreased by 21% to 64% in all patients (mean change, 44%; p < 0.05), and the clearance by O-demethylation was decreased by 20% to 69% in five of the patients (mean change in all patients, 35%; p < 0.05). In contrast, the partial clearance by 6-glucuronidation and the total systemic clearance of codeine were unchanged. Our results may be caused by the inhibition of growth hormone secretion induced by the somatostatins, inasmuch as direct metabolic interactions with these peptide drugs are improbable. The decline in CYP3A4 and CYP2D6 activity might have clinical implications when substrates of these enzymes with low therapeutic indices are combined with somatostatin analogs. Because the formation of morphine from codeine was altered, the analgesic effect of this drug may be reduced during concomitant treatment with somatostatins.

Pleural disease during treatment with bromocriptine in patients previously exposed to asbestos.

Bromocriptine, which is used in the treatment of Parkinson's disease, can cause adverse pleuropulmonary reactions. Exposure to asbestos can result in similar lesions. Fifteen patients with former exposure to asbestos, who developed pleural fibrosis after treatment with bromocriptine, were observed independently in Sweden (11 patients) and Australia (four patients). The patients complained of malaise, often associated with weight loss, dyspnoea, and a disturbing cough. Laboratory values included increased erythrocyte sedimentation rate and a low haemoglobin level. Lung function tests showed a restrictive lung function defect. Chest radiographs showed bilateral pleural fibrosis, with small amounts of fluid in some cases. Soon after bromocriptine was withdrawn, the patients improved clinically, and the laboratory values returned to normal. However, in most cases, pleural fibrosis and a restrictive lung function defect persisted to some extent. In conclusion, in patients who develop pleuropulmonary fibrosis whilst being treated with bromocriptine, former exposure to asbestos should be investigated. Conversely, when pleural changes develop in a patient on bromocriptine and with prior exposure to asbestos, the possible causative role of the drug should be discussed. Special follow-up may be indicated when bromocriptine is planned in a patient with previous asbestos exposure, and if symptoms or signs of pleural fibrosis develop, bromocriptine withdrawal should be considered.

[Iatrogenic rhinolithiasis?]. / Iatrogen rinolit?

A case of rhinolithiasis in a young man is presented. The radiological (CT-scan) and clinical findings of a rhinolith may be similar to other benign or malignant nasal lesion such as inverted papilloma. This similarity and the possibility that a rhinolith may have iatrogen origin is presented in this article.