Growth hormone response to low-dose apomorphine in restless legs syndrome.

INTRODUCTION: Low-dose apomorphine challenge has been shown to cause a rise in growth hormone (GH) in patients with Parkinson's disease (PD). This was interpreted as an increased postsynaptic sensitivity of hypothalamic dopamine receptors in the course of a generalized degeneration of dopaminergic neurons. The dopaminergic system in the restless legs syndrome (RLS) has been assumed to play a role in its pathophysiology. It is therefore the aim of this study to determine whether the GH response to subcutaneously applied low-dose apomorphine is generally altered in patients with RLS as compared to healthy controls. PATIENTS AND METHODS: We examined 40 patients with idiopathic RLS as well as 20 age- and sex-matched healthy control subjects by means of the low-dose apomorphine test. GH was analyzed at baseline, as well as 45 and 60 min after subcutaneous low-dose apomorphine injection in the morning. RESULTS: Forty RLS patients (58.3+/-11.9 years, 32 females) with a mean RLS severity scale score of 23.9+/-6.6 (range 10-37) were examined. GH was not significantly increased 45 and 60 min after injection (p=0.397) (2.44+/-2.35 ng/ml at baseline versus 2.71+/-2.29 ng/ml after 45 min and 2.18+/-1.83 ng/ml after 60 min). The results were independent of pre-treatment with levodopa. Age, sex, duration, and severity of the disease did not show a covariate effect with GH levels. There was no difference compared with healthy controls. CONCLUSIONS: RLS patients did not show an increase in GH after stimulation with low-dose apomorphine. Lack of sensitivity alteration of extrastriatal hypothalamic dopamine receptors suggests that RLS is not a general dopaminergic degenerative disease or might only show circadian alterations.     

L1 expression as a predictor of progression and survival in patients with uterine and ovarian carcinomas

Ovarian and uterine carcinomas are the most common cause of cancer-related deaths in gynecological malignant diseases. We aimed to assess whether the L1 adhesion molecule, an important mediator for cell migration for neural and tumour cells, is expressed in these carcinomas.     

A new animal model for bone atrophic nonunion: Fixation by external fixator

A new small animal model of bone atrophic nonunion was established for investigating the process of bone regeneration by performing cauterization of the periosteum, removal of the local bone marrow, and stabilization with external fixation. The model allows the creation of an atrophic nonunion without the need for a critical size defect. Furthermore, it provides reproducible, well‐defined mechanical conditions and minimized physical interference of the implant with the biological processes in the healing zone. Eighty adult Sprague‐Dawley rats received an osteotomy of the left femur, stabilized with an external fixator. In half of the animals, the periosteum proximal and distal to the osteotomy was destroyed by cauterization and the adjacent bone marrow was removed (nonunion group). At 2 and 8 weeks after surgery, radiological, biomechanical, histological, and histomorphometrical analyses showed a typical physiological healing in the control group, while the nonunion group was characterized by resorption of the bone ends with some callus formation distant to the osteotomy. At both time points, the callus was composed of significantly less bone and significantly more connective tissue (p < 0.001). In addition, the torsional strength of the osteotomized femur was significantly less in the nonunion group than in the control group, which was comparable to that of the intact femur (p < 0.001). In conclusion, the present model allows the induction of an atrophic nonunion without the need of a critical size defect. It is reproducible, provides standardized biomechanical conditions, and allows minimized interaction of the implant with the healing zone. © 2008 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res     

The adhesion molecule L1 (CD171) promotes melanoma progression

The adhesion molecule L1 is expressed in primary melanomas and cutaneous metastases in contrast to melanocytic nevi and melanocytes, and is significantly associated with metastatic spread. Recent studies have demonstrated that in carcinomas L1 expression is associated with sustained activation of the extracellular signal-regulated kinase (ERK) pathway and upregulation of ERK-dependent, motility- and invasion-associated gene products including alphavbeta3 integrin. The objective of this study was to further investigate the role of the adhesion molecule L1 in melanoma progression, and to evaluate whether targeting the L1 adhesion molecule would have therapeutic effects against invasive melanoma growth. Using human melanoma cells from different stages of progression in monolayer and organotypic human skin culture mimicking the pathophysiological environment of cutaneous melanoma, we found that (1) L1 expression mostly correlates with melanoma progression and alphavbeta3 integrin expression, (2) overexpression of L1 in early radial growth phase melanoma cells promotes conversion from radial to vertical growth phase melanoma without upregulation of alphavbeta3 integrin expression, and (3) suppression of L1 function significantly reduces migration and invasion of melanoma cells, but does not completely block invasive melanoma growth. Altogether, L1 plays a critical role in melanoma invasion and progression and offers therapeutic potential in combination with conventional anticancer agents.     

Reemergence of gram-negative health care-associated bloodstream infections

BACKGROUND: Primary health care-associated bloodstream infections (PHA-BSIs) affect as many as 350 000 patients in the United States annually. Whereas gram-negative organisms were the leading cause before the 1970s, gram-positive organisms have been the predominant microbial isolates since then. METHODS: We identified all PHA-BSIs among adult inpatients in a 625-bed quaternary care hospital from January 1, 1996, through December 31, 2003, and evaluated trends in the microbial etiology, geographic distribution within the institution, and antimicrobial susceptibilities. RESULTS: A total of 3662 PHA-BSIs caused by 4349 bacterial and fungal isolates were identified. From 1999 to 2003, the proportion of PHA-BSIs due to gram-negative organisms increased from 15.9% to 24.1% (P<.001 for trend). This trend was not significantly different across various units of the hospital, and no specific gram-negative species contributed disproportionately to the increase. With few exceptions, there were no significant increases in antimicrobial resistance. The increase in gram-negative organisms was accompanied by a decline in the proportion of PHA-BSIs from coagulase-negative staphylococci (from 33.5% in 1999 to 29.9% in 2003, P = .007) and from Staphylococcus aureus (from 18.8% in 1999 to 11.8% in 2003, P = .004). The proportion of PHA-BSIs from Candida species almost doubled from 5.8% in 1999 to 11.3% in 2003 (P = .002). CONCLUSIONS: To our knowledge, this is the first US study to report a reemergence of gram-negative organisms as a cause of PHA-BSIs. This finding does not seem to be related to changes in specific gram-negative organisms or to antimicrobial resistance. If this trend continues, it will have important implications for the management of bloodstream infections.     

Familiality of obsessive-compulsive disorder in nonclinical and clinical subjects

OBJECTIVE: Studies of the familiality of obsessive-compulsive disorder (OCD) have yielded inconsistent results. This study compared the familial aggregation of OCD in first-degree relatives of community subjects with never-treated OCD, outpatients with OCD, and comparison subjects. METHOD: Fifteen persons from the community with untreated OCD were matched on age and interview type (direct or through family informants) with 90 OCD patients from four treatment facilities and 70 comparison subjects. Direct or indirect interviews using the German-language version of the Schedule for Affective Disorders and Schizophrenia-Lifetime Version for Anxiety Disorders (DSM-IV) were obtained from 58, 285, and 247 first-degree relatives, respectively, of the three groups. The rate of OCD in case versus comparison relatives was assessed with chi-square tests, and odds ratios were calculated for risk estimation. Cox proportional hazards analysis was used to estimate the age-related risk of relatives of being affected by OCD. RESULTS: Cox proportional hazards analyses revealed a 6.2-fold higher risk (hazard ratio) for relatives of all OCD cases for definite OCD and a 2.2-fold higher risk for subclinical OCD compared with relatives of comparison subjects. For relatives of community subjects with OCD, the risk for definite OCD (10.3% versus 5.6%) was 1.6, and the risk for subclinical OCD (15.4% versus 4.1%) was 3.4 compared with relatives of OCD patients from treatment sites. CONCLUSIONS: These results from the first controlled European family study of OCD confirm earlier U.S. data on the familiality of OCD in patients recruited from treatment facilities. The finding of a comparable familial aggregation of definite OCD and a higher familial aggregation of subclinical OCD in relatives of never-treated persons with OCD from the community strongly supports the impact of familial-genetic factors in OCD.