Osteonecrosis of the Upper Extremity: MRI-Based Zonal Patterns and Differential Diagnosis.

Regarding the upper extremity, osteonecrosis can relate to the humeral head and to any carpal bone, most commonly the lunate (Kienböck's disease), scaphoid (Preiser's disease and nonunion), and capitate bone (osteonecrosis of the capitate head). In children and adolescents, osteochondrosis is an important differential diagnosis at the epiphyses. Appropriate imaging of osteonecrosis depends on knowledge about blood supply, biomechanical load, and bone repair mechanisms. Contrast-enhanced MRI (ceMRI) enables the differentiation of up to three mostly band-shaped zones: necrotic tissue (proximal), hypervascular repair tissue (intermediate), and viable bone (distal). To distinguish between necrotic and repair zones, intravenous gadolinium is recommended in MRI. Osteosclerosis and insufficiency fractures in early and intermediate stages as well as osteoarthritis in advanced stages are best depicted using high-resolution CT (HRCT). The combination of HRCT and ceMRI allows for exact classification of osteonecrosis regarding morphology and viability.

Clinical parameters of ovarian hyperstimulation syndrome following different hormonal triggers of oocyte maturation in IVF treatment.

OBJECTIVE: Ovarian hyperstimulation syndrome (OHSS) is a serious iatrogenic condition, predominantly related to the hormone used to induce oocyte maturation during IVF treatment. Kisspeptin is a hypothalamic neuropeptide that has recently been demonstrated to safely trigger final oocyte maturation during IVF treatment even in women at high risk of OHSS. However, to date, the safety of kisspeptin has not been compared to current hormonal triggers of oocyte maturation. DESIGN: We conducted a retrospective single-centre cohort study investigating symptoms and clinical parameters of early OHSS in women at high risk of OHSS (antral follicle count or total number of follicles on day of trigger ≥23) triggered with human chorionic gonadotrophin (hCG) (n = 40), GnRH agonist (GnRHa; n = 99) or kisspeptin (n = 122) at Hammersmith Hospital IVF unit, London, UK (2013-2016). RESULTS: Clinical Parameters of OHSS: Median ovarian volume was larger following hCG (138 ml) than GnRHa (73 ml; P < .0001), and in turn kisspeptin (44 ml; P < .0001). Median ovarian volume remained enlarged 20-fold following hCG, 8-fold following GnRHa and 5-fold following kisspeptin compared to prestimulation ovarian volumes. Mean (±SD) ascitic volumes were lesser following GnRHa (9 ± 44 ml) and kisspeptin (5 ± 8 ml) than hCG (62 ± 84 ml; P < .0001). Symptoms of OHSS were most frequent following hCG and least frequent following kisspeptin. Diagnosis of OHSS: The odds ratio for OHSS diagnosis was 33.6 (CI 12.6-89.5) following hCG and 3.6 (CI 1.8-7.1) following GnRHa, when compared to kisspeptin. CONCLUSION: Triggering oocyte maturation by inducing endogenous gonadotrophin release is preferable to the use of exogenous hCG in women at high risk of OHSS.

The direct and indirect effects of kisspeptin-54 on granulosa lutein cell function.

STUDY QUESTION: What are the in vivo and in vitro actions of kisspeptin-54 on the expression of genes involved in ovarian reproductive function, steroidogenesis and ovarian hyperstimulation syndrome (OHSS) in granulosa lutein (GL) cells when compared with traditional triggers of oocyte maturation? SUMMARY ANSWER: The use of kisspeptin-54 as an oocyte maturation trigger augmented expression of genes involved in ovarian steroidogenesis in human GL cells including, FSH receptor (FSHR), LH/hCG receptor (LHCGR), steroid acute regulatory protein (STAR), aromatase, estrogen receptors alpha and beta (ESR1, ESR2), 3-beta-hydroxysteroid dehydrogenase type 2 (3BHSD2) and inhibin A (INHBA), when compared to traditional maturation triggers, but did not alter markers of OHSS. WHAT IS KNOWN ALREADY: hCG is the most widely used trigger of oocyte maturation, but is associated with an increased risk of OHSS. The use of GnRH agonists to trigger oocyte maturation is a safer alternative to hCG. More recently, kisspeptin-54 has emerged as a novel therapeutic option that safely triggers oocyte maturation even in women at high risk of OHSS. Kisspeptin indirectly stimulates gonadotropin secretion by acting on hypothalamic GnRH neurons. Kisspeptin and its receptor are also expressed in the human ovary, but there is limited data on the direct action of kisspeptin on the ovary. STUDY DESIGN SIZE, DURATION: Forty-eight women undergoing IVF treatment for infertility consented to kisspeptin-54 triggering and/or granulosa cell collection and were included in the study. Twelve women received hCG, 12 received GnRH agonist and 24 received kisspeptin-54 to trigger oocyte maturation. In the kisspeptin-54 group, 12 received one injection of kisseptin-54 (9.6 nmol/kg) and 12 received two injections of kisspeptin-54 at a 10 h interval (9.6 nmol/kg × 2). PARTICIPANTS/MATERIALS, SETTING, METHODS: Follicular fluid was aspirated and pooled from follicles during the retrieval of oocytes for IVF/ICSI. GL cells were isolated and either RNA extracted immediately or cultured in vitro ± kisspeptin or hCG. MAIN RESULTS AND THE ROLE OF CHANCE: GL cells from women who had received kisspeptin-54 had a 14-fold and 8-fold higher gene expression of FSHR and a 2-fold (ns) and 2.5-fold (P < 0.05) higher expression of LHCGR than GL cells from women who had received hCG or GnRH agonist, respectively. CYP19A1 expression was 3.6-fold (P < 0.05) and 4.5-fold (P < 0.05) higher, STAR expression was 3.4-fold (P < 0.01) and 1.8-fold (P < 0.05) higher, HSD3B2 expression was 7.5- (P < 0.01) and 2.5-fold higher (P < 0.05), INHBA was 2.5-fold (P < 0.01) and 2.5-fold (P < 0.01) higher in GL cells from women who had received kisspeptin-54 than hCG or GnRHa, respectively. ESR1 (P < 0.05) and ESR2 (P < 0.05) both showed 3-fold higher expression in cells from kisspeptin treated than GnRHa treated women. Markers of vascular permeability and oocyte growth factors were unchanged (VEGFA, SERPINF1, CDH5, amphiregulin, epiregulin). Gene expression of kisspeptin receptor was unchanged. Whereas treating GL cells in vitro with hCG induced steroidogenic gene expression, kisspeptin-54 had no significant direct effects on either OHSS genes or steroidogenic genes. LIMITATIONS REASONS FOR CAUTION: Most women in the study had PCOS, which may limit applicability to other patient groups. For the analysis of the in vitro effects of kisspeptin-54, it is important to note that GL cells had already been exposed in vivo to an alternate maturation trigger. WIDER IMPLICATIONS OF THE FINDINGS: The profile of serum gonadotropins seen with kisspeptin administration compared to other triggers more closely resemble that of the natural cycle as compared with hCG. Thus, kisspeptin could potentially permit an ovarian environment augmented for steroidogenesis, in particular progesterone synthesis, which is required for embryo implantation. STUDY FUNDING/COMPETING INTEREST(S): Dr Owens is supported by an Imperial College London PhD Scholarship. Dr Abbara is supported by an National Institute of Health Research Academic Clinical Lectureship. The authors do not have any conflict of interest to declare. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov NCT01667406.

Multiple endocrine neoplasia 2 in Cyprus: evidence for a founder effect.

PURPOSE: Multiple endocrine neoplasia type 2 (MEN2) affects patients with RET proto-oncogene mutations. This cohort study refers to patients who were diagnosed with familial medullary thyroid carcinoma (MTC) and underwent RET genetic testing in Cyprus between years 2002 and 2017. METHODS AND PATIENTS: Forty patients underwent RET testing by Sanger sequencing of exons 10-11 and 13-16. Genotyping with STR genetic markers flanking the RET gene along with Y-chromosome genotyping and haplogroup assignment was also performed. RESULTS: RET mutations were identified in 40 patients from 11 apparently unrelated Cypriot families and two non-familial sporadic cases. Nine probands (69.2%) were heterozygous for p.Cys618Arg, one (7.7%) for p.Cys634Phe, one (7.7%) for the somatic delE632-L633 and two (15.4%) for p.Met918Thr mutations. The mean age at MTC diagnosis of patients carrying p.Cys618Arg was 36.8 ± 14.2 years. The age of pheo diagnosis ranged from 26 to 43 years and appeared simultaneously with MTC in 5/36 (13.9%) cases. The high frequency of the p.Cys618Arg mutation suggested a possible ancestral mutational event. Haplotype analysis was performed in families with and without p.Cys618Arg. Six microsatellite markers covering the RET gene and neighboring regions identified one core haplotype associated with all patients carrying p.Cys618Arg mutation. CONCLUSIONS: The mutation p.Cys618Arg is by far the most prevalent mutation in Cyprus followed by other reported mutations of variable clinical significance. The provided molecular evidence speculates p.Cys618Arg mutation as an ancestral mutation that has spread in Cyprus due to a possible founder effect.

Fibroids that do not distort the uterine cavity and IVF success rates: an observational study using extensive matching criteria.

OBJECTIVE: To assess the impact of non-cavity-distorting fibroids on in vitro fertilisation (IVF) pregnancy outcomes. DESIGN: A retrospective, matched, single-centre, cohort study was performed. SETTING: The IVF unit of a tertiary, university hospital. POPULATION: We analysed all women with non-cavity-distorting uterine fibroids undergoing IVF/intracytoplasmic sperm injection (ICSI) cycles from 1 January 2011 to 1 May 2015. METHODS: Each woman was matched with two separate controls of the same age (±6 months), stimulation protocol (gonadotropin-releasing hormone agonist or antagonist), starting dose of follicle-stimulating hormone (FSH), number of embryos transferred (one or two), day of transfer (day 3 or day 5), and no uterine fibroids identified by transvaginal ultrasound. MAIN OUTCOME MEASURES: Clinical pregnancy and live birth rates. RESULTS: Our study demonstrates that the presence of non-cavity-distorting fibroids appears to negatively affect clinical pregnancy (odds ratio, OR 0.62; 95% confidence interval, 95% CI 0.41-0.94) and live birth rates (OR 0.58; 95% CI 0.48-0.78) in patients undergoing their first IVF/ICSI cycle, when matched with controls of the same age, starting dose of FSH, stimulation protocol, number of embryos, and day of embryo transfer. The deleterious effect of fibroids on live birth rates was significant in women with two or more fibroids (OR 0.47; 95% CI 0.26-0.83) and in women with fibroids of ≥30 mm in diameter (OR 0.41; 95% CI 0.19-0.89). The negative impact of non-cavity-distorting fibroids was also present in women with an embryo transfer on day 5 (OR 0.58; 95% CI 0.35-0.94). Conversely, in women with single fibroids of <30 mm in diameter, no difference in pregnancy outcomes was identified. CONCLUSIONS: A well-designed, adequately powered, randomised controlled trial is required to address the role of medical or surgical interventions in patients with intramural and subserosal fibroids before undergoing fertility treatment. TWEETABLE ABSTRACT: Non-cavity-distorting fibroids negatively affect pregnancy rates after IVF.

Surgical skills of specialty trainees in emergency gynaecological laparoscopic procedures: a national UK survey.

A web-based survey was e-mailed to all specialty trainees ST Years 3-7 (n = 773) to assess their competence in emergency laparoscopic procedures. The trainees were asked about their competence level in a diagnostic laparoscopy; a salpingectomy; a salpingotomy; and an oophorectomy/cystectomy for adnexal torsion. Subsequently, they were asked how they would manage a tubal ectopic pregnancy with contralateral tubal disease. We received 202 responses (26%) and of these: 79% of trainees can perform a diagnostic laparoscopy independently; 32% can perform a salpingectomy and 12% can perform a salpingotomy independently; 14% can manage an adnexal torsion without supervision.

Interleukin-6 for the diagnosis of ovarian torsion: a systematic review and meta-analysis.

Ovarian torsion may have significant fertility implications. Interleukin-6 is a pro-inflammatory cytokine, which may act as a helpful diagnostic test. Our objective was to investigate the accuracy of serum interleukin-6 in the diagnosis of ovarian torsion in women with ultrasonographic evidence of an ovarian cyst. An electronic search of published data, unpublished dissertations, theses and conference proceedings was performed. The systematic review involved observational studies. The studies had to provide data to construct 2 × 2 tables. A modified QUADAS tool was used to assess the quality of studies. Sensitivity, specificity, positive and negative predictive value, likelihood ratios and diagnostic odds ratios were calculated. Three studies were identified. Two were included in the meta-analysis. The prevalence of torsion was 30% (21/70). The pooled sensitivity was 85.1% and the pooled specificity was 84.1%. Although further cohort studies would be required, there may be a role for interleukin-6 in the diagnosis of ovarian torsion.

Sonographic diagnosis of a neonatal gastric perforation presenting with scrotal swelling.

Neonatal gastric perforation is a rare, serious and frequently fatal condition of unclear etiology. The most common clinical presentation include tachypnea, respiratory distress, abdominal distension and cyanosis. We report an unusual case of neonatal gastric perforation presenting as erythematous scrotal swelling mimicking testicular torsion. This clinical presentation is unusual and early diagnosis and treatment is essential in order to prevent significant mortality and morbidity.

Genome-wide methylation profiling in granulosa lutein cells of women with polycystic ovary syndrome (PCOS).

Polycystic Ovary Syndrome (PCOS) is the most common endocrine disorder amongst women of reproductive age, whose aetiology remains unclear. To improve our understanding of the molecular mechanisms underlying the disease, we conducted a genome-wide DNA methylation profiling in granulosa lutein cells collected from 16 women suffering from PCOS, in comparison to 16 healthy controls. Samples were collected by follicular aspiration during routine egg collection for IVF treatment. Study groups were matched for age and BMI, did not suffer from other disease and were not taking confounding medication. Comparing women with polycystic versus normal ovarian morphology, after correcting for multiple comparisons, we identified 106 differentially methylated CpG sites with p-values <5.8 × 10-8 that were associated with 88 genes, several of which are known to relate either to PCOS or to ovarian function. Replication and validation of the experiment was done using pyrosequencing to analyse six of the identified differentially methylated sites. Pathway analysis indicated potential disruption in canonical pathways and gene networks that are, amongst other, associated with cancer, cardiogenesis, Hedgehog signalling and immune response. In conclusion, these novel findings indicate that women with PCOS display epigenetic changes in ovarian granulosa cells that may be associated with the heterogeneity of the disorder.

Expression of genes controlling steroid metabolism and action in granulosa-lutein cells of women with polycystic ovaries.

INTRODUCTION: Aberrant function of granulosa cells has been implicated in the pathophysiology of PCOS. MATERIALS & METHODS: Granulosa lutein (GL) cells were collected during oocyte retrieval for IVF/ICSI. RT-qPCR was used to compare gene expression between 12 control women, 12 with ovulatory PCO and 12 with anovulatory PCOS. To examine which genes are directly regulated by androgens, GL cells from an additional 12 control women were treated in-vitro with 10 nM dihydrotestosterone (DHT). RESULTS: GL cells from women with PCOS showed reduced expression of CYP11A1 3-fold (p = 0.005), HSD17B1 1.8-fold (p = 0.02) and increased expression of SULT1E1 7-fold (p = 0.0003). Similar results were seen in ovulatory women with PCO. GL cells treated with 10 nM DHT showed a 4-fold (p = 0.03) increase in expression of SULT1E1 and a 5-fold reduction in SRD5A1 (p = 0.03). CONCLUSIONS: These findings support the notion that aberrant regulation of steroid metabolism or action play a part in ovarian dysfunction in PCOS.

[Differential diagnosis of the signal-compromised lunate in MRI]. / Zur Differenzialdiagnostik des "signalkompromittierten" Os lunatum in der MR-Tomographie.

PURPOSE: To define both the underlying pathology and diagnostic criteria in lunates presenting with conspicuous signal pattern in MRI. MATERIALS AND METHODS: The retrospective evaluation of 2940 MRI examinations revealed 203 patients with signal alterations of the lunate. All MRI examinations were performed on 1.5-Tesla platforms using dedicated surface coils and an intravenous contrast agent. To establish a definitive diagnosis, a total of 252 MRI examinations (49 follow-ups), 22 CT examinations and 4 arthroscopic studies were obtained in addition to the obligatory conventional radiographs. RESULTS: Incorporating all clinical data, radiographs and MRI examinations succeeded in assigning a diagnosis in 136 signal-compromised lunates (67.0 %), whereas additional diagnostic procedures or follow-up examinations were required for the definitive diagnosis in 57 cases (33.0 %). The most frequent entities were 51 cases of Kienbock's disease (25.1 %), 47 cases of ulnolunate-(triquetral) impaction syndromes (23.2 %) and 44 cases of intra-osseous ganglion cysts (21.7 %). Other pathologies included 23 degenerative, 19 traumatic and 10 inflammatory changes as well as 9 congenital conditions. For MRI assessment of the altered lunate, the most important parameters were location and morphology as well as involvement of the articular and osseous structures of the carpus. CONCLUSION: The lunate may be affected by different pathological states of the wrist. In total, only one quarter of the signal-compromised lunate represented Kienboeck's disease.

Homologous regulation of the rat C1a calcitonin receptor (CTR) in nonosteoclastic cells is independent of CTR messenger ribonucleic acid changes and cyclic adenosine 3',5'-monophosphate-dependent protein kinase activation.

UMR106-06 cells predominantly express the C1a isoform of the rat calcitonin (CT) receptor (CTR). We have compared the homologous regulation of the C1a CTR endogenously expressed in UMR106-06 cells with the cloned C1a CTR in transfected HEK 293 cells, in which expression is driven by a heterologous promoter. It was found that treatment of both cell lines with either salmon CT or human CT reduced the density of cell surface CTR in a dose- and time-dependent manner. However, the magnitude of the response was greater in UMR106-06 cells, and salmon CT was more potent than human CT in both cell lines. Recovery from down-regulation was rapid in transfected cells (< 2 h), but was comparatively delayed in UMR106-06 cells, where less than 70% of receptor-binding capacity had returned by 24 h. In both cell lines, treatment with either agonist increased the basal activity of CT-sensitive adenylate cyclase and caused a time-dependent reduction in the responsiveness of adenylate cyclase to a second challenge with CT. Reduced responsiveness occurred under conditions of minimal loss of CTR from the cell surface, consistent with an uncoupling of the receptor from the signal transduction apparatus. Recovery of CT-sensitive adenylate cyclase was complete in transfected cells by 24 h, but was delayed in UMR106-06 cells, paralleling the slow recovery of receptor binding. CT-induced down-regulation of the CTR was not mimicked by receptor-independent activation of protein kinase A or protein kinase C. However, treatment of cells for 24 h, but not for 4 h, with phorbol ester caused a partial loss of CTR binding in UMR106-06 cells and resulted in an approximately 200% increase in CTR binding in transfected HEK 293 cells. CTR messenger RNA levels, as assessed by reverse transcription-PCR, were not changed by any of the above treatments. These results suggest that CT-induced receptor down-regulation and modulation of the ability of CT to activate adenylate cyclase are inherent properties of the receptor, as they can be recapitulated in an otherwise CTR-naive cell line, in which receptor expression is driven by a heterologous gene promoter. Moreover, and in contrast with CTR regulation in osteoclasts, activation of protein kinase A is insufficient for ligand-induced regulation of the CTR in these nonosteoclastic cell lines, and receptor regulation does not appear to involve altered messenger RNA levels.

Characterization of amylin and calcitonin receptor binding in the mouse alpha-thyroid-stimulating hormone thyrotroph cell line.

Recently, a high affinity amylin binding site was identified in the mouse alpha-TSH thyrotroph cell line. In this study, we have characterized binding sites for 125I-salmon calcitonin (125I-sCT), 125I-rat alpha-calcitonin gene-related peptide (125I-CGRP), and 125I-rat amylin in alpha-TSH cells. Using 125I-CGRP or 125I-rat amylin, equilibrium was rapidly reached, and binding was fully reversible. Competition binding revealed the relative potency of peptides was sCT>amylin, CGRP>>rCT, which is similar to the specificity profile of amylin receptors characterized in rat brain. Furthermore, specific binding of 125I-rat amylin and 125I-CGRP to membrane preparations was reduced by 52% and 39%, respectively, in the presence of 20 microM GTP-gamma-s, indicating a requirement of G protein coupling for high affinity binding. In contrast, 125I-sCT binding reached equilibrium more slowly, was essentially irreversible, and was unaltered by GTP-gamma-s. Competition binding studies using 125I-sCT as radioligand demonstrated only weak interaction by CGRP or amylin, consistent with other described CT receptors. Assessment of ligand-induced cAMP accumulation and intracellular calcium signaling revealed a relative specificity profile of sCT>rCT with little or no second messenger signaling stimulated by amylin or CGRP, consistent with a C1-CT receptor phenotype. RT-PCR amplification of messenger RNA indicated that the predominant isoform was the C1a CT receptor. In cross-linking studies, 125I-rat amylin and 125I-CGRP specifically labeled a major band of relative molecular mass (Mr) approximately 80K, being approximately 10 kDa higher than the major 125I-sCT binding protein. Full deglycosylation of N-linked carbohydrates with endoglycosidase F reduced the Mr of each of the labeled proteins to approximately 50K. Cross-linked amylin or CT receptors were immunoprecipitated with C-terminally directed antimouse or antirat CT receptor antibodies but were not immunoprecipitated with nonimmune sera or antihuman CT receptor antibodies. The current data demonstrate expression of two biochemically distinct receptor phenotypes in mouse alpha-TSH cells, a CT receptor phenotype and an amylin receptor phenotype that have highly similar protein backbones.

Detection of Duchenne and Becker muscular dystrophy carriers by quantitative multiplex polymerase chain reaction analysis.

We developed a method for the detection of Duchenne muscular dystrophy (DMD) and Becker muscular dystrophy (BMD) carriers. The method is based on the quantitative analysis of the products of standard multiplex polymerase chain reaction (PCR) from 18 different exons of the dystrophin gene, and is designated "QM-PCR." We detected deletions of one or more exons by standard multiplex PCR in DMD/BMD patients in 14 of 18 families examined (77.7%). The same deletions were readily demonstrated by QM-PCR in nine of 14 mothers (64.3%) and in another six of 22 possible carriers in these families. In five families where deletions were detectable in DMD/BMD patients, the mothers did not exhibit any deletions in their peripheral blood (35.7%). We obtained evidence for germinal mosaicism in at least two of these families and confirmed carrier identification by haplotype analysis using CA repeat polymorphisms at the 5' and 3' ends of the dystrophin gene. Furthermore, analysis of 17 coded DNA samples from normal females and obligatory carriers by QM-PCR showed that this technique could directly identify carriers of deletions in any of 18 different exons of the dystrophin gene. Its application in combination with existing techniques is expected to significantly improve the accuracy of carrier diagnosis in many families, and it may also be applicable to families in which pedigree and polymorphism information is insufficient for carrier diagnosis.

In vitro autoradiographic localization of calcitonin and amylin binding sites in monkey brain.

Calcitonin (CT) and amylin are related peptides with potent central actions, including suppression of appetite and gastric acid secretion. Little is known about the distribution and binding characteristics of amylin receptors in species other than rat; therefore, in this study, by using in vitro autoradiography, we have mapped the distribution of 125I-rat amylin binding sites in the monkey brain and compared this distribution to that of binding sites for 125I-salmon CT (125I-sCT). Highest densities of 125I-amylin binding were in the hypothalamus, including the arcuate nucleus and parts of the ventromedial hypothalamic nuclei, and the solitary nucleus. Rostrally, moderate to high density binding was present in parts of the preoptic area, bed nucleus of the stria terminalis, amygdala and accumbens nucleus (Acb). Caudally, binding of amylin was more restricted, with moderate to high density binding present only in dorsal raphe, and area postrema. The primary visual cortex displayed strong and periodic CT binding in layer 4. The subcortical pattern of distribution of amylin and CT receptors in the monkey was similar to that seen previously in the rat, although the relative densities of binding to different brain structures were not always conserved. As with rat, monkey amylin receptors were a subset of the sites labeled with 125I-sCT. Analysis of receptor specificity indicated a greater relative potency of CT peptides in competing for 125I-amylin binding in monkey, when compared to rat, while, there was a decrease in the relative potency of CT gene-related peptides, potentially due to differences the level of receptor activity modifying proteins (RAMPs) in monkey versus rat brain. Amylin receptors in primates are likely to perform a similar role to those in rats; however, the interaction of the receptors with related peptides may differ.

Asymptomatic pericarditis in Adamantiadis-Behçet's disease.

Pericardial involvement in Adamantiadis-Behçet's disease (ABD) is uncommon. A 14-year-old boy presented with fever of unknown origin, as the initial and only manifestation of his disease. Other features were leukopenia, abdominal lymphadenopathy and asymptomatic pericarditis, which is a very rare finding of the disease. A review of pericarditis is presented.

Neonatal screening for Duchenne muscular dystrophy: a novel semiquantitative application of the bioluminescence test for creatine kinase in a pilot national program in Cyprus.

The objectives of this study were to evaluate a novel semiquantitative application of the bioluminescence test for screening newborns for Duchenne muscular dystrophy (DMD) and to use this technique in a pilot national program. The study was performed on the island of Cyprus, which provides ideal conditions for maximizing the prevention rate due to the small size of the country, the well-defined population, and the high degree of awareness of the public concerning genetic diseases. Guthrie spots were obtained through the national screening center for phenylketonuria and congenital hypothyroidism. The bioluminescence method for measuring creatine kinase (CK) in dried blood spots was adapted for use in a semiquantitative way. During the first 6 years of the program (1992-1997), we screened 30,014 samples and found 43 with initially high CK values. We were able to obtain repeat specimens in 35 cases. Of the repeat samples, 30 were found to have normal activity, giving a false-positive rate of 0.10%. Five boys had persistent CK elevations and were confirmed to be DMD or Becker (BMD) cases by DNA analysis and/or dystrophin analysis. The semiquantitative application of the bioluminescence assay of CK that we have introduced has proved to be a fast and reliable method for screening large numbers of samples for DMD. It has a low rate of false positives, which compares favorably with that of other DMD screening programs. Although it is early to evaluate its impact fully, the program seems to be bringing about the anticipated benefits to affected families.

[Direct MR arthrography of the wrist in comparison with arthroscopy: a prospective study on 125 patients]. / Direkte MR-Arthrographie des Handgelenks im Vergleich zur Arthroskopie: Eine prospektive Studie an 125 Patienten.

OBJECTIVE: In literature the diagnostic value of MRI for detecting lesions of the carpal ligaments and the TFCC is judged controversially. The aim of the following study is to determine the diagnostic accuracy of direct MR arthrography for depicting and staging of intraarticular lesions of the wrist. MATERIAL AND METHODS: One day before undergoing arthroscopy, 125 patients suffering from wrist pain were examined with direct MR arthrography in a prospective and blinded study. A mixture of contrast medium (iodine-containing contrast medium and gadopentetate in relation 200 : 1) was injected into both radiocarpal and midcarpal joints. The following sequences were acquired on a 1.5T scanner: coronal T1-weighted SE, coronal fat-saturated T1-weighted SE, coronal T1-/T2*-DESS-3D, and sagittal T2*-weighted MEDIC. MRI results were compared with arthroscopic findings using statistical analysis (SEN = sensitivity, SPE = specificity, PPV = positive predictive value, NPV = negative predictive value, ACC = accuracy). RESULTS: In comparison to arthroscopy as the accepted diagnostic gold standard, the following results were found for MR arthrography. Detection of TFCC lesions: SEN 97.1 %, SPE 96.4 %, PPV 97.1 %, NPV 96.4 %, ACC 96.8 %. Detection of complete tears of the scapholunate ligament: SEN 91.7 %, SPE 100 %, PPV 100 %, NPV 99.1%, ACC 99.2%. Detection of partial tears: SEN 62.5 %, SPE 100 %, PPV 100 %, NPV 94.8 %, ACC 95.2 %. Detection of cartilage defects: SEN 84.2 %, SPE 96.2 %, PPV 80 %, NPV 97.1 %, ACC 94.4 %. In total, only three lesions of the lunotriquetral ligament were present. CONCLUSION: Direct MR arthrographic imaging is well suited for detecting intraarticular lesions of the wrist. The presented diagnostic results of MR arthrography are superior to the results of unenhanced MRI reported in the literature. Direct MR arthrography as a reliable diagnostic tool is strongly recommended if lesions of the scapholunate ligament and the triangular fibrocartilage complex are suspected. In contrast, an attitude of caution must be adopted in diagnosing lesions of the articular cartilage of the wrist.

[Scapholunate ligament tears in MR arthrography compared with wrist arthroscopy]. / Darstellung skapholunärer Verletzungen im Arthro-MRT im Vergleich zur Handgelenkarthroskopie.

In a blinded study from January to July 2000, 125 patients suffering from specific complaints of the wrist were prospectively examined with direct MR arthrography. Within 24 hours an arthroscopy of the wrist was performed. With MR arthrography in 21 patients or 17 % of all patients, injury of the scapho-lunate ligament was diagnosed. In all patients this could be verified arthroscopically. In the remaining 104 patients, no SL-ligament lesions were diagnosed with the MR arthrography. However, partial lesions were found via arthroscopy in seven cases and complete lesions of the ligament were found in one case, where MRI findings expected an intact SL ligament. In the remaining 96 cases, the MRI could correctly exclude a lesion of the SL-ligament. The diagnosis of a SL-ligament lesion by means of MRI was correct in 100 % of the cases (specificity), the exclusion of such lesions in 72 % (sensitivity). Positive or negative predictive values of 100 % or 92 % were achieved. Since a sensitivity of 100 % cannot be reached at the moment, MR arthrography cannot replace arthroscopy. However, it could be a potent additional tool for wrist diagnosis if intraarticular contrast is used. It can facilitate the diagnostics and the indication for surgery of the wrist and help to reduce arthroscopic interventions for purely diagnostic purposes and without any therapeutic consequences. With improvement of the technique of magnet resonance tomography we can expect a further increase of accuracy in the clinical use of the MR arthrography in the diagnostic workup of the wrist.

[Melorheostosis of the hand. A case report]. / Die Melorheostose der Hand. Ein Fallbericht.

Summary. Melorheostosis is a sclerosing disease commonly affecting the bone, rarely soft tissue. Etiology is unknown. It causes uncharacteristic symptoms such as pain, joint stiffness, soft tissue contractures, and limb deformities. Standard radiology reveals the diagnosis. Until now there is no standard therapy. Melorheostosis is a rare bone dysplasia and important as a differential diagnosis for tumorous changes in the limb or in painful joints.