A case report of a patient with metastatic ocular melanoma who experienced a response to treatment with the BRAF inhibitor vemurafenib.

BACKGROUND: Conjunctival malignant melanoma (CMM) is a rare malignancy and in the advanced setting there is no effective treatment. In contrast, half of cutaneous melanomas have BRAF mutations and treatment with BRAF inhibitors is established for patients with disseminated disease. The most common form of ocular melanoma, uveal melanoma, lacks these mutations, however, their presence has been reported for CMM. CASE PRESENTATION: We used the BRAF inhibitor vemurafenib to treat a 53 year-old female suffering from a BRAF(V600E) mutated metastatic CMM. The patient benefited from the treatment, a response was evident within a week and she experienced a progression free survival of four months. CONCLUSIONS: To our knowledge, this is the first described case of response to vemurafenib treatment in a patient with ocular melanoma.

LXR is a negative regulator of glucose uptake in human adipocytes.

AIMS/HYPOTHESIS: Obesity increases the risk of developing type 2 diabetes mellitus, characterised by impaired insulin-mediated glucose uptake in peripheral tissues. Liver X receptor (LXR) is a positive regulator of adipocyte glucose transport in murine models and a possible target for diabetes treatment. However, the levels of LXRα are increased in obese adipose tissue in humans. We aimed to investigate the transcriptome of LXR and the role of LXR in the regulation of glucose uptake in primary human adipocytes. METHODS: The insulin responsiveness of human adipocytes differentiated in vitro was characterised, adipocytes were treated with the LXR agonist GW3965 and global transcriptome profiling was determined by microarray, followed by quantitative RT-PCR (qRT-PCR), western blot and ELISA. Basal and insulin-stimulated glucose uptake was measured and the effect on plasma membrane translocation of glucose transporter 4 (GLUT4) was assayed. RESULTS: LXR activation resulted in transcriptional suppression of several insulin signalling genes, such as AKT2, SORBS1 and CAV1, but caused only minor changes (<15%) in microRNA expression. Activation of LXR impaired the plasma membrane translocation of GLUT4, but not the expression of its gene, SLC2A4. LXR activation also diminished insulin-stimulated glucose transport and lipogenesis in adipocytes obtained from overweight individuals. Furthermore, AKT2 expression was reduced in obese adipose tissue, and AKT2 and SORBS1 expression was inversely correlated with BMI and HOMA index. CONCLUSIONS/INTERPRETATION: In contrast to murine models, LXR downregulates insulin-stimulated glucose uptake in human adipocytes from overweight individuals. This could be due to suppression of Akt2, c-Cbl-associated protein and caveolin-1. These findings challenge the idea of LXR as a drug target in the treatment of diabetes.

When to order a biopsy to characterise a metastatic relapse in breast cancer.

Today, the diagnosis of metastatic breast cancer is usually based on radiological findings, and therapeutic decisions are made by considering the pathological characteristics and predictive markers of the primary tumour. Accumulating evidence suggests that tumour characteristics, including estrogen receptor (ER) and human epidermal growth factor receptor 2 (HER2), are unstable through tumour progression. Several retrospective studies and, recently, two prospective studies have investigated the discrepancies in receptor status between primary tumours and the corresponding metastases in a total of 1773 patients (for ER) and 2845 patients (for HER2). Changes in ER and HER2 status in these studies range from 14.5% to 40% and from 0% to 37.5%, respectively. In the two prospective studies, a different diagnosis, usually non-malignant, was obtained in 3% and 9% of the cases, and the biopsy led to a treatment modification in about one out of seven patients. Here, we review and discuss the currently available data and provide our recommendations on when a metastatic biopsy should be obtained.

Individually tailored treatment with epirubicin and paclitaxel with or without capecitabine as first-line chemotherapy in metastatic breast cancer: a randomized multicenter trial.

Anthracyclines and taxanes are active cytotoxic drugs in the treatment of early metastatic breast cancer. It is yet unclear whether addition of capecitabine to the combination of these drugs improves the treatment outcome. Patients with advanced breast cancer were randomized to first-line chemotherapy with a combination of epirubicin (Farmorubicin(®)) and paclitaxel (Taxol(®)) alone (ET) or in combination with capecitabine (Xeloda(®), TEX). Starting doses for ET were epirubicin 75 mg/m(2) plus paclitaxel 175 mg/m(2), and for TEX epirubicin 75 mg/m(2), paclitaxel 155 mg/m(2), and capecitabine 825 mg/m(2) BID for 14 days. Subsequently, doses were tailored related to side effects. Primary endpoint was progression-free survival (PFS); secondary endpoints were overall survival (OS), time to treatment failure (TTF), objective response (OR), safety and quality of life (QoL). 287 patients were randomized, 143 to ET and 144 to TEX. Median PFS was 10.8 months for patients treated with ET, and 12.4 months for those treated with TEX (HR 0.84, 95% CI 0.65-1.07, P = 0.16); median OS was 26.0 months for women in the ET versus 29.7 months in the TEX arm (HR 0.84, 95% CI 0.63-1.11, P = 0.22). OR was achieved in 44.8% (ET) and 54.2% (TEX), respectively (χ(2) 3.66, P = 0.16). TTF was significantly longer for patients treated with TEX, 6.0 months, versus 5.2 months following ET (HR 0.73, 95% CI 0.58-0.93, P = 0.009). Severe hematological side effects related to epirubicin and paclitaxel were evenly distributed between the treatment arms, mucositis, diarrhea, and Hand-Foot syndrome were significantly more frequent in the TEX arm. Toxicity-adjusted treatment with ET and TEX showed similar efficacy in terms of PFS, OS, and OR. In this trial with limited power, the addition of capecitabine to epirubicin and paclitaxel as first-line treatment did not translate into clinically relevant improvement of the outcome.

Primary differences in lipolysis between human omental and subcutaneous adipose tissue observed using in vitro differentiated adipocytes.

Catecholamine-induced lipolysis is elevated in omental as compared to subcutaneous adipocytes due to primary differences between the two cell types (i.e., they have different progenitor cells). Whether there is regional variation in atrial natriuretic peptide (ANP)-induced lipolysis is unknown. We studied whether beta-adrenoceptor signaling to lipolysis and ANP-induced lipolysis are involved in the primary differences in lipolysis. In vitro experiments on differentiated preadipocytes from human subcutaneous and omental adipose tissue were performed. The cells were kept in culture for a relative long duration, so any influence of local environment and circulation in the various adipose tissue depots could be excluded. Using beta1-, beta2-, and beta3-adenoceptor agonists, lipolysis was found to be significantly higher in omental as compared to subcutaneous differentiated preadipocytes. Forskolin and dibutyryl cAMP, which act at post-adrenoceptor levels, did not show any regional difference. There was no regional difference in ANP-induced lipolysis. Gene expression of beta1- and beta3-adrenoceptors was higher and beta2-adrenoceptor expression was lower in the omental cells. Omental fat cells have an increased beta-adrenoceptor-mediated lipolysis principally due to primary differences in the early event that couples beta-adrenoceptor subtypes to G-proteins. ANP-induced lipolysis is not subject to primary regional variation.

Endothelin-1 stimulates human adipocyte lipolysis through the ET A receptor.

OBJECTIVE: Levels of the vascular peptide endothelin-1 (ET-1) are significantly elevated in obesity. Adipose tissue-derived ET-1 attenuates insulin-mediated antilipolysis in human visceral adipocytes through the activation of the ET receptor B (ET(B)R), thereby linking ET-1 to insulin resistance. Whether ET-1 has direct effects on lipolysis in human adipocytes is not known. RESEARCH DESIGN AND SUBJECTS: Endothelin-1 receptor (ETR) mRNA expression was determined by quantitative PCR in 130 non-obese and obese subjects. ET-1 mRNA in different adipose tissue regions was also assessed. ETR protein expression was analyzed by western blotting in 37 subjects. The effect of ET-1 on lipolysis was assessed in freshly isolated adipocytes and in vitro differentiated adipocytes from human donors. RESULTS: Freshly isolated human adipocytes incubated with different concentrations of ET-1 showed no acute effect on lipolysis. In contrast, a 24 h incubation in primary cultures of human adipocytes resulted in a significant 50% increase in lipolysis. This effect was concentration dependent and could be mimicked by an agonist of the ET(A) receptor but not with a selective ET(B)R agonist. Adipocyte differentiation was not affected by any of the agonists. In subcutaneous (s.c.) adipose tissue from 19 non-obese and 18 obese subjects, the protein expression of ET(A)R was significantly higher in obese subjects whereas there was no difference in ET(B)R expression. Interestingly, the differences in protein expression were not observed at the mRNA level as ET(A)R expression was similar between lean and obese subjects. CONCLUSION: Long-term but not acute incubation of human adipocytes with ET-1 results in a significant increase in lipolysis. This appears to be mediated through the activation of ET(A)R, demonstrating a yet another receptor-specific effect of ET-1. In addition, the protein expression of ET(A)R is increased in s.c. adipose tissue in obesity, possibly through post-transcriptional mechanisms. An increased effect of ET-1 could be a mechanism that contributes to increased basal lipolysis in human obesity.

The influence of preadipocyte differentiation capacity on lipolysis in human mature adipocytes.

The ability of catecholamines to maximally stimulate adipocyte lipolysis (lipolytic capacity) is decreased in obesity. It is not known whether the lipolytic capacity is determined by the ability of adipocytes to differentiate. The aim of the study was to investigate if lipolytic capacity is related to preadipocyte differentiation and if the latter can predict lipolysis in mature adipocytes. IN VITRO experiments were performed on differentiating preadipocytes and isolated mature adipocytes from human subcutaneous adipose tissue. In preadipocytes, noradrenaline-induced lipolysis increased significantly until terminal differentiation (day 12). However, changes in the expression of genes involved in lipolysis (hormone sensitive lipase, adipocyte triglyceride lipase, the alpha2-and beta1-adrenoceptors, perilipin, and fatty acid binding protein) reached a plateau much earlier during differentiation (day 8). A significant positive correlation between lipolysis in differentiated preadipocytes and mature adipocytes was observed for noradrenaline (r=0.5, p<0.01). The late differentiation capacity of preadipocytes measured as glycerol-3-phosphate dehydrogenase activity was positively correlated with noradrenaline-induced lipolysis in preadipocytes (r=0.51, p<0.005) and mature fat cells (r=0.35, p<0.05). In conclusion, intrinsic properties related to terminal differentiation determine the ability of catecholamines to maximally stimulate lipolysis in fat cells. The inability to undergo full differentiation might in part explain the low lipolytic capacity of fat cells among the obese.

Total and differential leucocyte counts and lymphocyte subpopulations in lymph, afferent and efferent to the supramammary lymph node, during endotoxin-induced bovine mastitis.

Leucocyte trafficking in afferent and efferent mammary lymph and the supramammary lymph node in cows was examined during 4 h after intramammary infusion of endotoxin from Escherichia coli. Total and differential leucocyte counts were measured in milk, blood and lymph. The proportions of CD4(+), CD8(+), major histocompatibility complex (MHC) class II(+) and IgM(+) lymphocytes were examined in the lymph and lymph node. At post-infusion hour (PIH) 4, the flow rates of both lymph fluids had increased approximately eightfold. Total leucocyte concentration increased in afferent lymph, but decreased in efferent lymph. Neutrophils increased in afferent lymph at PIH 2 and in efferent lymph and milk at PIH 4. The predominant cell type in afferent lymph shifted from lymphocyte to neutrophil while lymphocyte was still at PIH 4 the predominant type in efferent lymph. Among the lymphocytes, B cells were predominant in afferent lymph and lymph node at PIH 4 while T cells, mainly CD4(+) cells, were predominant in efferent lymph both at PIH 0 and PIH 4. The CD4 : CD8 ratio was higher in efferent lymph and the challenged lymph node than in afferent lymph and the control node, respectively. There was a significant difference in proportions of each lymphocyte subpopulation except for IgM(+) cells, between afferent and efferent lymph after infusion. According to the results, there was already during the first hours of the immune response, a non-random trafficking of neutrophils and lymphocyte subpopulations resulting in a changed distribution of cells in afferent and efferent lymph and a difference in lymphocyte reactivity between the two lymph fluids.

Differential function of the alpha2A-adrenoceptor and Phosphodiesterase-3B in human adipocytes of different origin.

OBJECTIVE: Human adipocytes can be obtained in vitro by differentiation of human preadipocytes or mesenchymal stem cells (hMSC). Although functionally similar to freshly isolated cells, no detailed comparison of the different cell types has been performed. The antilipolytic alpha2A-adrenoceptor (AR) and the cAMP-degrading enzyme Phosphodiesterase-3B (PDE3B) have been implicated in the fine-tuning of lipolysis but little is known regarding their role in human adipocytes nor whether their expression and/or function differs in fat cells from different precursors. METHODS: The effects of alpha2A-AR and PDE3B inhibition in mature adipocytes was determined and compared to that in differentiated preadipocytes and hMSC-derived fat cells. Gene expression was determined by real-time PCR and protein expression by Western blot. RESULTS: Noradrenaline (NA) stimulated lipolysis in preadipocytes and mature adipocytes but markedly reduced lipolysis in differentiated hMSC derived-adipocytes. This was due to a potent stimulation of alpha2A-AR since co-incubation with NA and the alpha2-AR-inhibitor yohimbine restored NA-induced lipolysis. The order of Yohimbine response was hMSC>preadipocytes>mature adipocytes. Although alpha2-AR mRNA expression was highest in mature adipocytes there was no difference in alpha2A-AR protein levels between the cell types. In contrast, Galphai2 mRNA and protein expression was significantly higher in MSC-derived adipocytes, suggesting that differences in the response to alpha2A-AR inhibition reside at the postreceptor level. Incubation with the cAMP-analog 8-bromo(8b) cAMP increased lipolysis in hMSC-derived fat cells while co-incubation with the PDE3-specific inhibitor OPC3911 did not alter the lipolytic effect. In contrast, OPC3911 increased 8bcAMP-induced lipolysis significantly in preadipocytes and mature adipocytes. The response to PDE3B inhibition was; mature adipocytes>preadipocytes>hMSC a finding that correlated significantly with both PDE3B mRNA expression and enzymatic activity. CONCLUSION: Although differentiated adipocytes of different origins display similar functional characteristics there are important differences in the regulation of lipolysis with a marked alpha2A-AR and less pronounced PDE3B effect in fat cells from MSCs.

Chemical-shift micro-imaging of subcutaneous lesions.

A chemical-shift imaging technique was used for the study of small subcutaneous lesions. This study concerns micro-imaging of two females suffering from a tenosynovial giant cell tumor and an epidermal cyst. High-resolution water, fat and chemical-shift artifact-free images were obtained on a whole-body MR unit (1.5 T) equipped with a 23-mm microscopy surface coil and standard gradients (23 mT/m). A significant improvement in signal-to-noise ratio was achieved by reducing the receiver bandwidth to values below +/-10 kHz. The image data sets were acquired with resolution 0.1 x 0.13 mm in the plane, slice thickness 0.5 mm and with acquisition time less than 3 min. Spatial resolution, fat suppression, image texture and edge delineation were improved on spectroscopic images compared with those on conventional MR images.

Effect of granulocyte colony-stimulating factor (G-CSF)-supported chemotherapy on MR imaging of normal red bone marrow in breast cancer patients with focal bone metastases.

PURPOSE: To investigate the effect of granulocyte colony-stimulating factor (G-CSF)-supported chemotherapy on normal red bone marrow MR imaging in breast cancer patients with focal bone metastases. MATERIAL AND METHODS: Fifteen breast cancer patients who were examined before and after chemotherapy with T1-weighted-SE and long echo-time inversion-recovery turbo-spin-echo (long TE IR-TSE) sequences in the thoracolumbar spine and pelvis were retrospectively studied. Nine of them received G-CSF therapy after the administration of each chemotherapy course. Of these 9 patients, the MR follow-ups were performed during G-CSF in 4 patients and after G-CSF therapy in 5 patients. Six patients did not receive G-CSF. Signal intensity (SI) changes in normal bone marrow were evaluated visually in all patients and quantitatively in 13 patients. RESULTS: In all 4 patients investigated during G-CSF therapy a diffuse, homogeneous SI increase on long TE IR-TSE was observed visually and quantitatively in initially normal bone marrow. This change obscured some focal lesions in 2 patients. No such SI change was visible after G-CSF therapy (p = 0.008) or in patients not receiving G-CSF. On T1-weighted images an SI decrease was found both during and after G-CSF therapy, but an increase occurred in patients not receiving G-CSF. CONCLUSION: G-CSF-supported chemotherapy can induce diffuse SI changes in normal red bone marrow on MR imaging. On long TE IR-TSE, the changes are visible during G-CSF treatment and can lead to misinterpretations in the response evaluation of bone metastases to therapy.

Nicotinamide prevents the long-term effects of perinatal asphyxia on basal ganglia monoamine systems in the rat.

Asphyxia during birth can cause gross brain damage, but also subtle perturbations expressed as biochemical or motor deficits with late onset in life. Thus, it has been shown that brain dopamine levels can be increased or decreased depending upon the severity of the insult, and the region where the levels are determined. In this study, perinatal asphyxia was evoked by immersing pup-containing uterus horns removed by hysterectomy in a water bath at 37 degrees C for various periods of time from 0 to 20 min. After the insult, the pups were delivered, given to surrogate mothers, treated with nicotinamide, further observed and finally, 4 weeks later, killed for monoamine biochemistry of tissue samples taken from substantia nigra, neostriatum and nucleus accumbens. The main effect of perinatal asphyxia was a decrease in dopamine and metabolite levels in nucleus accumbens, and a paradoxical increase in the substantia nigra. Nicotinamide (100 mg/kg i.p., once a day for 3 days, beginning 24 h after the perinatal asphyctic insult) prevented the effect of asphyxia in nucleus accumbens. Furthermore, striatal dopamine levels were increased by nicotinamide in asphyctic animals. No apparent changes were observed in substantia nigra. A prominent unexpected effect of perinatal asphyxia alone was on the levels of the metabolite of 5-hydroxytryptamine, 5-hydroxyindoleacetic acid (5-HIAA), which were increased in substantia nigra and decreased in both neostriatum and accumbens. However, nicotinamide increased 5-HIAA levels in all regions, which appeared to be related to the extent of the asphyctic insult. These results suggest that nicotinamide is a useful treatment against the long-term consequences produced by perinatal asphyxia on brain monoamine systems, and that there is a therapeutic window following the insult, providing a therapeutic opportunity to protect the brain.

Diagnosis of a patient with oncogenic osteomalacia using a phosphate uptake bioassay of serum and magnetic resonance imaging.

A previously healthy man with no family history of fractures presented with muscle pain, back pain and height loss. Investigations revealed hypophosphataemia, phosphaturia, undetectable serum 1,25-dihydroxyvitamin D and severe osteomalacia on bone biopsy, suggestive of a diagnosis of oncogenic osteomalacia. Thorough physical examination did not locate a tumour. Support for the diagnosis was obtained by detection of phosphate uptake inhibitory activity in a blinded sample of the patient's serum using a renal cell bioassay. On the basis of detection of this bioactivity, a total body magnetic resonance (MR) examination was performed. A small tumour was located in the right leg. Removal of the tumour resulted in the rapid reversal of symptoms and the abnormal biochemistry typical of oncogenic osteomalacia. Inhibitory activity was also demonstrated using the bioassay in serum from two other patients with confirmed or presumptive oncogenic osteomalacia, but not in serum from two patients with hypophosphataemia of other origin. This is the first case to be reported in which the diagnosis of oncogenic osteomalacia was assisted by demonstration of inhibitory activity of the patient's serum in a renal cell phosphate bioassay that provided an impetus for total body MR imaging.

Spectroscopic imaging of bone marrow composition in vertebral bodies.

The proton spectroscopic imaging technique that uses read gradient during acquisition was used for the measurement of the proton spectra in the lumbar and thoracic part of the spine of a patient with breast cancer without known skeletal metastases. The bone marrow fat/water ratios were evaluated in the same location before and after chemotherapy treatment. The results were corrected for relaxation effects. The fat/water ratios showed a significant increase as a consequence of the bone marrow degradation process due to chemotherapy. The proposed spectroscopic imaging technique offers rapid acquisition of proton spectra from large volumes of the vertebral bodies.

High-resolution spectroscopic imaging of the human skin.

High-resolution water, fat and chemical shift artefact-free images of different areas of the skin were obtained on a whole-body MR unit (1.5 T) with commercial receiver surface coil with a diameter of 25 mm and high-power gradients (23 mT/m). Sufficient signal-to-noise ratio was achieved by lowering receiver bandwidth to +/-10 kHz or lower and shortening the echo time to 11 (13) ms. Spectroscopic image data sets were acquired with resolution 0.102 x 0.133 mm in plane and slice thickness 0.5 mm. The results demonstrate that it is possible to produce high-quality water and fat micro-images of the skin layers using only a few chemical shift encoding steps in a clinically reasonable time (approximately 2 minutes per slice).

A care policy and its implementation.

Chief physicians, nurse managers and head nurses (n = 50) in hospital care and primary health care in Västerbotten, Sweden, were interviewed to explore their views on adopting and implementing a new care policy. The results indicated agreement among the respondents concerning the values of the care policy and its adaptability to the health-care system. More respondents in hospital care than in primary health care expressed a positive view (63%, respectively 55%), reported involvement in the implementation process (64%, respectively 35%) and planned or ongoing activities (63%, respectively 45%). Obstacles in the implementation process due to a frustrated situation and barriers between professional groups were, however, expressed by 67% of the respondents, more among the respondents in primary health care than among those in hospital care (75%, respectively 62%). Divergent views among respondents working in the same department were seen in both hospital care and primary health care. The findings indicated demands for further efforts if the implementation is to move on from its early stages, especially in primary health care.

Endoanal ultrasound or magnetic resonance imaging for preoperative assessment of anal fistula: a comparative study.

OBJECTIVE: To compare endoanal ultrasound (EUS) with a 10-MHz probe vs. bodycoil magnetic resonance imaging (MRI) in the preoperative evaluation of anal fistula. SUBJECTS AND METHODS: 23 patients with fistula in the anal region underwent preoperative 0.5 T bodycoil MRI and 10 MHz EUS which included probing in 6 patients. The results of the EUS and MRI were compared against the surgical findings as a reference method. RESULTS: In classification of the primary tract there was agreement between EUS and surgical findings in 14 (61%) and between MRI and surgery in 11 (48%). Concerning the presence of an internal opening the corresponding figures were 17 (74%) and 10 (43%) and in judging the presence of an extension or an abscess 15 (65%) vs. 11 (48%), respectively. In three out of eight patients with nonhealing or recurrence after surgery preoperative imaging had shown an extension and/or an abscess that was not identified by the surgeon. CONCLUSION: EUS, sometimes complemented with probing, is well comparable to bodycoil MRI in classifying and describing the topography of an anal fistula.

Value of transsternal core biopsy in patients with a newly diagnosed mediastinal mass.

Histopathologic analysis of an anterior mediastinal mass of unknown origin is essential for treatment decision. Mediastinoscopy is the most common procedure performed to obtain biopsies, but general anaesthesia and hospitalization are necessary. The aim of this study was to evaluate whether transsternal core biopsies, an easy outpatient biopsy technique, could be an alternative to mediastinoscopy. A biopsy instrument that makes it possible to reach tumours hidden behind bone was used for transsternal CT-guided core biopsies in 21 patients with a newly diagnosed anterior mediastinal mass. No severe side effects were observed. In 19/21 (90%) patients the biopsies were diagnostic. In 2/21 patients additional biopsy techniques had to be used. In these two patients Hodgkin's disease was suspected in the first biopsy procedures. The diagnosis was confirmed by new core biopsies, from other parts of the tumour, not using a transsternal approach (transclavicular and parasternal, respectively). In addition, one mediastinoscopy was performed in a patient who was diagnosed with a non-Hodgkin's lymphoma but where more material was needed for lymphoma subclassification. It is concluded that CT-guided transsternal core biopsy is a clinically valuable method in patients with a newly diagnosed anterior mediastinal mass.

Evaluation of new sclerotic bone metastases in breast cancer patients during treatment.

PURPOSE: According to the World Health Organization (WHO) criteria for response of bone metastases to therapy, new lesions indicate progressive disease. We intended to prove that a new sclerotic lesion on conventional radiography may also be a sign of a positive therapeutic response in a previously undetectable lytic metastasis. MATERIAL AND METHODS: In a previous placebo-controlled clinical trial of clodronate (Ostac) therapy, 139 breast cancer patients with bone metastases underwent both conventional radiography and bone scan every 6 months for 2 years with 99mTc before and during clodronate treatment. WHO criteria were applied for therapy response evaluation. RESULTS: In 24 patients, 52 new sclerotic lesions observed during therapy were selected for re-evaluation of conventional radiographs and bone scans. In 8 of the 24 patients, 17 of 52 new sclerotic lesions (33%) had showed positive uptake on previous bone scans. These lesions were possibly misinterpreted as new when applying WHO criteria. CONCLUSION: For better assessment of new sclerotic lesions during treatment, more sensitive techniques, e.g. bone scan, are needed as a complement to conventional radiography.

Use of novel bone biopsy system to study molecular effects of growth hormone in human bone--a pilot study.

In this study, we have examined whether a novel bone biopsy system combined with reverse transcription-polymerase chain reaction (RT-PCR) or differential display PCR (ddPCR) can be used to detect specific mRNAs induced by growth hormone (GH) in human bone. In a 58-year-old man with complete GH deficiency as a result of empty sella, bone biopsies were taken before, and 5 and 24 h after administration of 24 recombinant human GH. Insulin-like growth factor binding protein-3 (IGFBP-3) mRNA levels in this patient, measured in a semiquantitative RT-PCR assay, increased about 40% 24 h after GH administration. This increase was not seen in a healthy control who did not receive GH, suggesting that the increase was an effect of GH rather than of the biopsy itself. Several differentially expressed mRNAs were detected by ddPCR. Thus, this pilot study suggests that our novel bone biopsy system may be suitable for in vivo studies of the molecular effects of substances with essential functions in human bone.