Biomedical subjects

G Wolf

Publications and source records attributed to G Wolf.

At least 289 records · Page 16Linked to original sources

PubMed1997

[Management of suspected malignant nodular goiter in pregnancy].

Guidelines for the management of thyroid nodules supposed to be malignant during pregnancy have not yet been established. We recommend performance of fine needle biopsy in thyroid nodules having developed during pregnancy, and in preexisting thyroid nodules suspicious of being malignant, respectively. According to literature, surgical intervention in case of papillary carcinoma can be postponed to a timepoint soon after delivery. Regarding the management of follicular or medullary cancer, sufficient data are not available. In threatening cases, i.e. in case of rapid growth of the nodule(s) or suspected high malignancy, surgery can be done at any time. Nevertheless, pregnancy itself neither seems to promote growth of thyroid cancer nor to have any impact on the dignity of cancer.

Adenocarcinoma, Follicular↗

PubMed1997

[Thyroid gland surgery in pregnancy].

Thyroid carcinoma is more frequent in younger women, but direct correlation with pregnancy is not proven. Preoperative management of suspect nodules reveals clear indications for immediate intervention. Out on 1471 thyroid operations, 340 female were in the group between 20 and 40 years. 53 carcinoma, i.e. 3.6%, in this subgroup had a potential concomittance of pregnancy and thyroid tumor. Although risk of obortion is very low in non-abdominal surgery, operations should be delayed post-partum except in cases of proven carcinoma.

Abortion, Spontaneous↗

PubMed1997

[Comparative genomic hybridization of bronchial carcinomas and their metastases].

We analysed 150 carcinomas of the respiratory tract and their metastases by Comparative Genomic Hybridization (CGH), a screening method for the detection of chromosomal imbalances in solid tumors. Small cell lung carcinomas (SCLC) and non-small cell lung carcinomas (NSCLC) revealed characteristic patterns of chromosomal alterations with overlapping and specific lesions in both tumor groups. SCLC were defined by a pattern of deletions on chromosomes 3p, 4q, 5q, 10q, 13q and 17p along with overrepresentations of chromosomes 3q and 5p. In contrast, NSCLC carried frequently deletions on chromosomes 1p, 3p, 4q, 5q, 6q, 8p, 9p, 13q, 18q and 21q along with overrepresentations of chromosomes 5p and 11q13. The deletions of the chromosomal band 2q36-q37 together with amplifications of chromosome 3q were statistically significant lesions of squamous cell carcinomas (SCC) whereas adenocarcinomas were characterized in particular by the overrepresentation of chromosome 1q23 and the deletion on chromosome 9q22. The comparison of primary and metastatic tumors revealed that the deletion of chromosome 10q was a statistically significant marker of tumor progression and metastatic phenotype in SCC and SCLC. In conclusion, the data indicate that tumor histotypes and phenotypes are associated with patterns of chromosomal alterations which give important additional information for the classification of human lung carcinomas.

Adenocarcinoma↗

PubMed1997

Image analysis for comparative genomic hybridization based on a karyotyping program for windows.

OBJECTIVE: To describe the image processing and analysis techniques we developed for the quantitative analysis of comparative genomic hybridization (CGH). STUDY DESIGN: A system for CGH cytometry is based on a semiautomated karyotyping program using the Windows graphic user interface. RESULTS: After alignment and normalization of the fluorescence images of the test genome (FITC) and reference genome (TRITC), the chromosomes are segmented and arranged as a CGH karyogram. The CGH karyograms from different metaphases of one tumor sample are represented as a CGH sum karyogram. Mean DAPI, FITC, TRITC and RATIO images, as well as ratio profiles with the 95% confidence interval, can be displayed. CONCLUSION: Representation of CGH results in the form of pseudocolored mean ratio chromosomes enhances the visibility of the method. The ratio profile plus confidence interval facilitates the identification of preparation artifacts and the classification of chromosomal imbalances. The sum karyograms of several tumors can be combined into a CGH superkaryogram of a tumor subgroup; that helps identify recurrent DNA changes in a tumor and might lead to genetic tumor classification based on CGH.

DNA, Neoplasm↗

PubMed1996

Tyrosine-phosphorylated Cbl binds to Crk after T cell activation.

Crk is a Src homology 2 (SH2)/Src homology 3 (SH3)-containing adapter protein that has been implicated in intracellular signaling in fibroblasts and PC12 pheochromocytoma cells. Crk has been shown to bind to a tyrosine-phosphorylated protein of 116 kDa after TCR-mediated T cell activation. Here we demonstrate that the Crk-associated p116 phosphoprotein is not the Crk-associated substrate (Cas) but, rather, is a protein product of the c-cbl proto-oncogene. Whereas Cas was not tyrosine-phosphorylated after T cell activation, Cbl became highly phosphorylated. Crk immunoprecipitates from activated T cell lysates contain tyrosine-phosphorylated Cbl. This association is mediated by the SH2 domain of Crk, as evidenced by the interaction between Cbl and the fusion protein product of a glutathione S-transferase (GST) expression construct encoding the Crk-SH2 domain in vitro. Furthermore, phosphopeptide-binding studies revealed that the GST-Crk SH2 domain binds to a tyrosine-phosphorylated peptide corresponding to amino acids 770-781 of Cbl with high affinity. Cbl is a protein tyrosine kinase (PTK) substrate that becomes phosphorylated after engagement of numerous cell surface receptors including the TCR. Data revealed by genetic studies in the nematode, Caenorhabditis elegans, implicates a Cbl-like molecule, Sli-1, as a negative regulator of the Let-23-signaling pathway. Because the signal from the Let-23 pathway affects the activation status of the Let-60 (Ras homologue in C. elegans) pathway, the activation-dependent association between Crk and Cbl may represent another TCR-generated signal leading to Ras-related pathways.

Amino Acid Sequence↗

PubMed1996

Oxidized low-density lipoprotein stimulates protein kinase C (PKC) and induces expression of PKC-isotypes via prostaglandin-H-synthase in P388D1 macrophage-like cells.

Treatment of cells with LPS-free oxLDL significantly enhanced protein kinase C (PKC) activity in cell extracts from P388D1 macrophage-like cells as determined by phosphorylation of histone H1 or Ac-MBP[4-14] substrate peptide. This effect was abolished by the PKC inhibitors H-7 and bisindolylmaleimide I while pertussis toxin failed to block stimulation. The phosphotransferase activity was also increased by acetylated LDL (acLDL) and maleylated albumin (malBSA), the oxLDL effect was inhibited by chloroquine which also blocked oxLDL-induced stimulation of tyrosine kinase activity. Marginal stimulation of PKC activity was observed when lipid extracts from oxLDL were used, indicating that uptake via scavenger receptors (SR) is mandatory. Polyinosinic acid (poly I) exhibited a concentration-dependent inhibition of the oxLDL-induced effect suggesting that SR II/I but not CD36 interactions are critical to PKC activation. Modified (lipo)proteins increased the concentration of diacylglycerol and differentially affected the levels of individual PKC isoenzymes predominantly in the cytosolic fraction. Changes of activity induced by oxLDL could be primarily assigned to alterations of the activities and levels of the isoenzymes beta and delta. Treatment with oxLDL, acLDL, and malBSA was also accompanied by increased production of prostaglandins as well as by an enhanced level of cyclooxygenase 2 (COX 2) as determined by Western blot analysis. Effects (correction) of oxLDL on PKC activity/expression was suppressed by the cyclooxygenase, 2,2-dimethyl-6-(4-chlorophenyl)-7-phenyl-2,2-dihydro-1H-pyrrolizine-5- ylacetic acid (ML 3000), and by treatment with the specific COX 2-inhibitor N-(2-cyclohexyloxy-4-nitrophenyl) methane-sulfonamide (NS-398). These results indicate that oxLDL, acLDL, and malBSA exhibit a COX 2-dependent and isotype specific effect on PKC in P388D1 cells following uptake via SR II/I and subsequent lysosomal degradation.

Animals↗

PubMed1996

Interaction between the Grb10 SH2 domain and the insulin receptor carboxyl terminus.

Grb10 is a member of a recently identified family of adapter proteins that are thought to play a role in receptor tyrosine kinase-mediated signal transduction. We identified and isolated the Grb10 SH2 domain based on its interaction with the intracellular domain of the insulin receptor beta-subunit using the yeast two-hybrid system. The interaction was specific for the insulin receptor and the insulin-like growth factor-1 receptor, and it required a catalytically active receptor kinase domain and an intact Grb10 SH2 domain. Glutathione S-transferase fusion proteins containing the Grb10 SH2 domain associated in an insulin-dependent manner with insulin receptors from cell lysates and with purified insulin receptors. Co-precipitation experiments revealed the association of cellular Grb10 with hormone-stimulated insulin receptors in cell extracts. The Grb10 SH2 domain did not bind to an insulin receptor lacking 43 amino acids at the carboxyl terminus, and it exhibited highest affinity for a phosphopeptide containing Tyr(P)-1322. Unlike p85 and Syp, which also bind to Tyr(P)-1322, Grb10 was not found to associate with insulin receptor substrate-1. These results suggest that Grb10 is a novel insulin receptor interactive protein and provide direct evidence for an insulin receptor substrate-1-independent function of the insulin receptor carboxyl terminus in protein binding.

3T3 Cells↗

PubMed1996

4'-O-[2-(2-fluoromalonyl)]-L-tyrosine: a phosphotyrosyl mimic for the preparation of signal transduction inhibitory peptides.

Development of phosphotyrosyl (pTyr) mimetics which are stable to protein-tyrosine phosphatases (PTPs), yet can retain biological potency when incorporated into peptides, is an active area of drug development. Since a majority of pTyr mimetics derive their "phosphofunctionality" from phosphorus-containing moieties, such as phosphonates, evolution of new inhibitors and modes of prodrug derivatization have been restricted to chemistries appropriate for phosphorus-containing moieties. A new, nonphosphorus-containing pTyr mimetic has recently been reported, L-O-(2-malonyl)tyrosine (OMT,5), which can be incorporated into peptides that exhibit good PTP and Src homology 2 (SH2) domain inhibitory potency. For phosphonate-based pTyr mimetics such as phosphonomethyl phenylalanine (Pmp,2) introduction of fluorines alpha to the phosphorus has provided higher affinity pTyr mimetics. This strategy has now been applied to OMT, and herein is reported 4'-O-[2-(2-fluoromalonyl)]-L-tyrosine (FOMT,6) a new fluorine-containing nonphosphorus pTyr mimetic. Incorporation of FOMT into appropriate peptides results in good inhibition of both PTP and SH2 domains. In an assay measuring the inhibition of PTP 1B-mediated dephosphorylation of phosphorylated insulin receptor, the peptide Ac-D-A-D-E-X-L-amide exhibited a 10-fold enhancement in inhibitory potency for X = FOMT (19) (IC(50) = 10 microM) relative to the unfluorinated peptide, X = OMT (18) (IC(50) = 10 microM. Molecular modeling indicated that this increased affinity may be attributable to new hydrogen-bonding interactions between the fluorine and the enzyme catalytic site, and not due to lowering of pKa values. In a competition binding assay using the p85 PI 3-kinase C-terminal SH2 domain GST fusion construct, the inhibitory peptide, Ac-D-X-V-P-M-L-amide, showed no enhancement of inhibitory potency for X = FOMT (22) (IC(50) = 18 microM) relative to the unfluorinated peptide, X = OMT (21) (IC(50) = 14 microM). The use of FOMT would therefore appear to have particular potential for the development of PTP inhibitors.

Amino Acid Sequence↗

PubMed1996

Angiotensinase A gene expression and enzyme activity in isolated glomeruli of diabetic rats.

One of the characteristics of early diabetic nephropathy is glomerular hyperfiltration and hyperperfusion. Many factors have been suggested to induce glomerular hyperperfusion among which are an increased production of vasodilatory prostanoids, an increased synthesis of nitric oxide, a reduced responsiveness of afferent glomerular arterioles to vasoconstrictor stimuli due to diabetic metabolic disturbances and a decreased receptor density for angiotensin II. It has been known for years that angiotensin II is formed locally due to the local activation of the renin angiotensin system. The local angiotensin II concentration, however, is not only regulated by the synthesis rate but also by the local degradation through activation of an aminopeptidase. The main finding of the present study was that the mRNA expression and activity of the angiotensin II degrading enzyme, angiotensinase A, was increased twofold in diabetic rats at 5 weeks and that the increase in mRNA expression was suppressed by insulin therapy and short-term treatment with the angiotensin II antagonist saralasin, whereas angiotensinase A enzyme activity was only reduced by saralasin and not by insulin. These results demonstrate that the angiotensin II degrading exopeptidase angiotensinase A is activated in diabetic glomeruli. This increased activity may be an additional mechanism to explain glomerular hyperfiltration and hyperperfusion in early diabetic nephropathy.

Albuminuria↗

PubMed1996

Ultrastructural distribution of NADPH-diaphorase in the normal hippocampus and after long-term potentiation.

The distribution of the enzyme nitric oxide synthase (NOS) was investigated at the ultrastructural level in synaptic structures of the hippocampal formation in relation to long-term potentiation (LTP), based on the histochemical NADPH-diaphorase (NADPH-d) staining with the tetrazolium salt BSPT. BSPT-formazan, the osmiophilic reaction product, was found to be selectively distributed and predominantly attached to membranes of the endoplasmic reticulum. In synaptic regions mainly the presynaptic sides showed labeling. Although several groups have demonstrated a principal involvement of NO in the LTP-mechanism, we found only a low, statistically insignificant increase in NADPH-d stained presynaptic areas of the dentate gyrus, where LTP was evoked. Postsynaptic elements also did not show any noticeable differences. Based on the present results, the predominantly presynaptic localization of NOS should be preferably considered in models describing a functional role of NO in LTP formation, despite the fact that we failed to reveal any indications for an LTP-related change in synaptically located NADPH-d.

Animals↗

PubMed1996

Induction of cytosolic NADPH-diaphorase/nitric oxide synthase in reactive microglia/macrophages after quinolinic acid lesions in the rat striatum: an electron and light microscopical study.

Induction of nitric oxide synthase and increased production of nitric oxide in microglia may play a crucial role in neuronal damage and neurodegenerative disorders. In the present study we have used light and electron microscopical NADPH-diaphorase histochemistry as the visualization procedure for nitric oxide synthase to investigate the time-course and subcellular patterns of NADPH-diaphorase expression in microglia/macrophages of quinolinic acid-lesioned rat striatum. For light microscopy, NADPH-diaphorase histochemistry sections were stained with nitroblue tetrazolium, while for ultrastructural analysis the tetrazolium salt 2-(2'-benzothiazolyl)-5-styryl-3(4'-phthalhydrazidyl) tetrazolium chloride (BSPT) was applied. Light microscopical inspection revealed a progressively increasing number of positive cells with increasing intensity of NADPH-diaphorase staining in microglia/macrophages from day 1 after quinolinic acid injection onward. Electron microscopical examination revealed a membrane bound NADPH-diaphorase in quiescent microglia as well as in activated microglia/macrophages through all stages of the lesion studied. Predominantly membranes of the nuclear envelope and the endoplasmic reticulum were labeled with BSPT-formazan, while in advanced stages selective membrane portions of mitochondria, Golgi apparatus and plasmalemma were also stained. From day 5 onward after lesion induction, a very distinctive type of NADPH-diaphorase was observed, forming accumulations of electron-dense grains that were distributed differentially throughout cytoplasmic areas and phagocytic vacuoles. Dynamics of expression, unique cytosolic localization and occurrence exclusively in activated microglia/macrophages suggest that this particular NADPH-diaphorase activity probably reflects the inducible isoform of nitric oxide synthase, whereas the membrane-bound precipitate may represent the neuronal and/or the endothelial isoform of the enzyme.

Animals↗

PubMed1996

Polar body diagnosis of common aneuploidies by FISH.

PURPOSE: The purpose of this work was to investigate the reliability and accuracy of polar body analysis for preimplantation diagnosis of common aneuploidies in IVF patients of advanced maternal age. DESIGN: We have previously introduced polar body analysis as an approach for nondestractive evaluation of the genotype of human oocytes. The method has recently been applied in a clinical trial involving 45 infertile patients, demonstrating the feasibility of preconception diagnosis of common aneuploidies by fluorescent in situ hybridization (FISH). The present paper describes the experience of polar body diagnosis in 135 IVF patients (161 cycles) of advanced maternal age. RESULTS: FISH results of the first and/or second polar bodies were available in 648 (72.4%) of 895 biopsied oocytes subjected to FISH analysis. Of 648 oocytes with FISH results, 208 demonstrated chromosomal abnormalities. Of 440 oocytes predicted to be free from monosomy or trisomy of chromosomes X, 18, and/or 13/21, 314 were normally fertilized, cleaved, and transferred in 122 treatment cycles, resulting in 6 healthy deliveries and 12 ongoing pregnancies following confirmation of the polar body diagnosis by CVS or amniocentesis. CONCLUSIONS: The method may be useful for detection of oocytes with common chromosomal trisomies in IVF patients of advanced maternal age.

Abortion, Spontaneous↗

PubMed1996

[Analysis program for quantitative detection of chromosome aberrations using comparative genomic hybridization].

Comparative genomic hybridization (CGH) is a molecular cytogenetic method for the detection of chromosomal imbalances between a tumor and a normal genome. In order to produce quantitative and reproducible results, we developed an image analysis program that allows the detection and mapping of the genetic alterations. The result is represented as a CGH sum karyogram in which the genetic changes are documented as color coded-chromosomes. The aim of our investigation is to correlate the genotype with the phenotype on the basis of CGH sum karyograms and thus to achieve a genetic characterization that will supplement the morphological tumor description.

Cell Transformation, Neoplastic↗

PubMed1996

Patterns of nitric oxide synthase at the messenger RNA and protein levels during early rat brain development.

There is substantial evidence that the intra- and intercellular messenger nitric oxide, generated enzymatically from L-arginine by nitric oxide synthase in different isoforms, is involved in the development of nervous tissue. In this study we investigated the nitric oxide expression in the pre- and postnatally developing rat brain. With regard to messenger RNA, all of the basic nitric oxide synthase isoforms (neuronal, endothelial and macrophage nitric oxide synthase) were already expressed at embryonic day 10 and showed a temporary decrease at embryonic day 17. Western blot analysis of the three isoform proteins revealed a time pattern that was different from those of messenger RNAs. Although the endothelial nitric oxide synthase isoform was also expressed at embryonic day 10, no quantitative changes were observed over the whole time period studied. Protein amounts of brain and inducible nitric oxide synthase were first detectable at embryonic day 15, with a tendency to rise. A parallel time pattern was found for the NADPH-diaphorase activity in our light microscopic studies, whereas ultrastructurally the reaction product was seen in the brain pallium even of 13-day-old embryos. The data indicate a permanent presence of the transcripts for all nitric oxide synthase isoforms in the rat central nervous system from embryonic day 10 onwards, although the expression of respective proteins and staining patterns may differ.

Aging↗

PubMed1996

Use of resistance index for the diagnosis of breast tumours.

AIM: To determine whether the resistance index (RI) contributes to the differential diagnosis of breast masses. PATIENTS AND METHODS: In 56 breast tumours colour-coded Doppler sonography was performed and their resistance indices calculated from their spectral Doppler tracings. Histologic evaluation was obtained by excision biopsy. RESULTS: In seven of 28 benign tumours (25%) no lesion was seen on ultrasound. In another seven benign tumours, no intratumoral vessels were demonstrated. The resistance index of the remaining 14 lesions (50%) varied between 0.5 and 0.75 with a mean value of 0.62 (standard deviation 0.08). Ultrasound missed one of 28 carcinomas (3.5%) and in one other tumour (3.5%) no flow was demonstrable. The resistance index of 26 malignant tumours varied between 0.56 and 0.9 with a mean value of 0.7 (standard deviation 0.08). CONCLUSION: Breast malignancies have higher resistance indices with a wider range as assessed by colour-coded Doppler ultrasound (81% exceed 0.6) than do benign lesions. Due to the considerable overlap of the range of the resistance index, the measurements in any single patient may not be diagnostic. The absence of flow does not definitively exclude malignancy.

Adolescent↗

PubMed1996

Prostaglandin E1 inhibits collagen expression in anti-thymocyte antibody-induced glomerulonephritis: possible role of TGF beta.

To test whether or not prostaglandins mediate extracellular matrix formation in immune-mediated glomerular disease, rats with anti-thymocyte antibody-induced glomerulonephritis were treated with prostaglandin E1 (PGE1) (250 micrograms/twice daily/s.c.). Glomerular expression of collagen types III and IV was assessed by Northern blotting, immunohistology and Western blotting. Proliferation of glomerular cells was evaluated by staining for the proliferating cell nuclear antigen (PCNA) and consecutive cell counting. At day five after induction of the disease, glomerular mRNA levels of collagen types III and IV were three- to fivefold higher compared with non-nephritic controls. Similarly glomerular deposition of these collagens was markedly increased when assessed by immunohistology. The treatment of nephritic rats with PGE1 reduced the increased glomerular mRNA levels as well as the protein concentration and the deposition of extracellular collagens. The number of PCNA positive cells which was significantly higher in nephritic rats when compared with control animals (24 hr, nephritis 2.53 +/- 0.33 and Control 0.26 +/- 0.06, P = 0.011; 5 days, nephritis 5.10 +/- 1.13 and Control 0.75 +/- 0.08, cells per glomerular cross section, P = 0.03) was reduced by PGE1 (24 hr, nephritis+PGE1 0.44 +/- 0.30, P = 0.0001; 5 days, nephritis +/- PGE1 1.91 +/- 1.84 cells per glomerular cross section, P = 0.001). Prostaglandin E1 also ameliorated the glomerular infiltration of monocytes at 24 hours (nephritis 4.36 +/- 2.82, nephritis + PGE1 2.20 +/- 1.82, cells per glomerular cross section) and five days (nephritis 1.51 +/- 0.58, nephritis+PGE1 1.12 +/- 0.61, cells per glomerular cross section). To further characterize possible mechanisms by which PGE1 reduces extracellular matrix deposition, the glomerular expression of transforming growth factor (TGF-beta), and interleukin 1 beta (IL-1 beta) was assessed by Northern blotting. Nephritic glomeruli showed increased mRNA levels of TGF-beta at day 5 and IL-1 beta at 24 hours when compared with control kidneys. Treatment of the animals with PGE1 inhibited the mRNA expression of TGF-beta and IL-1 beta. These data demonstrate that PGE1 reduces the glomerular expression of extracellular matrix proteins in anti-thymocyte antibody-induced glomerulonephritis, suggesting a beneficial role of prostaglandins in this proliferative glomerular immune injury. The effects of PGE1 might be mediated by inhibition of TGF-beta and IL-1 beta production.

Alprostadil↗

PubMed1996

Angiotensin II-stimulated hypertrophy of LLC-PK1 cells depends on the induction of the cyclin-dependent kinase inhibitor p27Kip1.

Angiotensin II (Ang II) induces hypertrophy of cultured proximal tubular epithelial cells including the LLC-PK1 cell line. We have previously shown that this hypertrophy appears in the G1-phase of the cell cycle. Since progression through the cell cycle is controlled by a series of cyclin and cyclin-dependent kinase (CdK) complexes that may be inactivated by CdK inhibitors, we studied the expression of the CdK-inhibitor p27Kip1 in LLC-PK1 cells challenged with Ang II. Compared to cells grown in serum-free medium, Ang II treatment enhanced p27Kip1 protein, but not mRNA expression. This p27Kip1 induction was mediated through AT1-receptors. Exogenous TGF-beta also stimulated p27Kip1 protein expression. Immunoprecipitation experiments revealed that p27Kip1 preferentially associated with CdK4 in Ang II-treated LLC-PK1 cells and that the activity of this kinase was inhibited after Ang II-treatment, an effect that may be generated by increased p27Kip1 binding to cyclin D1-CdK4 complexes. In contrast, p27Kip1 was not associated with cyclin E-CdK2 complexes in Ang II-stimulated cells. Treatment of LLC-PK1 cells with p27Kip1 antisense, but not missense, oligonucleotides abolished the Ang II-mediated cell hypertrophy as measured by de novo protein synthesis and total protein content, and facilitated entry into the S-phase of the cell cycle. Our findings suggest that Ang II stimulates p27Kip1 expression in renal cells. Furthermore, this induction of the CdK-inhibitor appears pivotal in the hypertrophy induced by Ang II and elucidates the molecular mechanisms associated with this growth response in proximal tubular cells.

Angiotensin II↗

PubMed1996

Recovery from severe osteoporosis following cure from ectopic ACTH syndrome caused by an appendix carcinoid.

It is well established that endogenous overproduction of glucocorticoids may cause osteoporosis. However, knowledge about potential recovery of the skeleton after cessation of corticosteroid excess is limited. We describe a 34-year-old female patient and discuss the complex diagnostic workup that led to the rare diagnosis of carcinoid of the appendix as the cause of Cushing's syndrome. The patient experienced multiple spontaneous rip fractures, and at that time, the bone mineral density of the lumbar spine was 4.3 SD below values for age-matched healthy controls. After removal of the tumour, the patient completely recovered. Measurements at the lumbar spine showed an increase in area bone density of 79% equivalent to 4 SD over a subsequent 3-year observation period. This first case of documented bone mass recovery in a patient cured of ectopic ACTH syndrome suggests a potential for excellent reversibility of steroid-induced osteoporosis and should be considered in the management of such patients.

Adult↗