Idiopathic transient osteoporosis of the knee: five cases and revision of literature

Five patients with idiopathic transient osteoporosis were examined. Bone scanning and MRI was helpful in the diagnosis to differentiate of necrosis and all patients recovered completely with conservative and symptomatic treatment. There was no history of trauma in all patients. MRI was realized previously in all cases to confirm the diagnosis and after the resolution of symptomathology.     

Auxiliary production of antibodies to ocular antigens in experimental autoimmune uveoretinitis

In experimental autoimmune uveoretinitis (EAU), there are concurrent autoreactive humoral and cellular immune responses. Many studies have recently focused on T-cell reactivities in EAU, while analysis of autoantibody responses to uveitogenic epitopes has been less well characterized. In this study, a defined 16-mer uveitogenic interphotoreceptor retinoid binding protein (IRBP) peptide, designated #896, was used to induce EAU. Histological analysis of eyes at day 10 demonstrated extensive leukocyte infiltration of the anterior segment, with mononuclear and plasma cells in the posterior segment. The presence of plasma cells suggests local production of antibodies within the eye. ELISA analyses of serum, aqueous, and vitreous from rats with IRBP-induced, severe EAU revealed the presence of antibodies against peptide #896. There was little difference between the serum and intraocular antibody titers, presumably due to breakdown of the blood-ocular barriers. In addition to the anti-#896-IRBP antibodies, there were detectable antibodies reactive against separate and distinct IRBP epitopes, as well as, against epitopes on retinal-S antigen. These results indicate that in #896-peptide-induced severe EAU, humoral immune responses are induced to the primary immunogen and that there is also auxiliary production of autoreactive antibodies against other epitopes present on intraocular antigens. These auxiliary responses may contribute to the immunopathogenesis of severe EAU.     

Successful Liver and Kidney Transplantation From Cadaveric Donors With Left-Sided Bacterial Endocarditis

Bacterial infections are frequent in cadaveric organ donors and can be transmitted to the transplantation recipient, which could have devastating consequences for the recipients if adequate preventive measures are not adopted.
From the 355 consecutive brain dead cadaveric organ donors procured at our center in the last four years, 2000–2003, four of them (1.1%) had bacterial endocarditis as cause of death. The bacteria responsible for the endocarditis were Staphylococcus epidermidis, coagulase-negative Staphylococcus , Staphylococcus hominis and Streptococcus viridans , respectively. We performed five kidney and two liver transplantations on seven recipients. All donors and recipients received antibiotic treatment against the germ causing the respective endocarditis.
Infection by the bacteria responsible for the endocarditis in the respective donors was not transmitted to any of the recipients. Six of the seven recipients were alive with normal-functioning grafts after between 13 and 24 months' follow-up. Transplantectomy was performed on one kidney recipient due to thrombosis of the renal vein of the graft not related to the endocarditis.
Liver and kidney transplantation from donors dying from bacterial endocarditis can be performed without causing the transmission of infection to the recipient or the dysfunction of the graft.     

IRBP: preparation and characterization of site-specific monoclonal antibodies.

Interstitial retinoid binding protein (IRBP) is a 136,000 molecular weight photoreceptor cell protein which is a highly pathogenic autoantigen for the induction of experimental autoimmune uveitis (EAU). In this study we produced a series of monoclonal antibodies (MAbs) which define different epitopes in the native molecule. These MAbs were further subdivided into three distinct groups based on a radioimmunoassay, and by ELISA assay using native IRBP and synthetic peptides corresponding to its entire amino acid sequence. Group I MAbs (MAbD7-B1 and MAbC6-B4) bound to native IRBP but not to any synthetic peptides, suggesting that their antigenic epitopes are strictly conformation dependent. Group II MAbs (MAbC7-D3 and MAbG8-H4) bound weakly to multiple peptides which shared amino acid sequence similarity located within each of four homology domains indicating that these epitopes are also conformation dependent. In group III (MAbH3-B5, MAbH7-A5, and MAbB6-D12) MAb binding was localized to a specific peptide. The MAbH3-B5 binding site was further refined to amino acid positions 361 to 367 in the native molecule. MAbH3-B5 was also useful in localizing IRBP in the mouse retina by immunohistochemical techniques. The application of these MAbs in the study of EAU and interphotoreceptor transport mechanisms is discussed.     

Predicting spontaneous early neurological recovery after acute ischemic stroke

We assessed predictors of spontaneous early neurological recovery after acute ischemic stroke by means of multivariate analysis in a cohort of 1,473 consecutive patients treated at one academic center. At hospital discharge, spontaneous neurological improvement or good outcome was defined as grades 0-2 of the Rankin scale, and poor outcome (no improvement or in-hospital death) as grades 3-5. Spontaneous recovery of neurological deficit at the time of discharge from the hospital was observed in 16% of patients with cerebral infarction (n = 238). Dysarthria-clumsy hand syndrome improved in 44% of patients and was the only variable significantly associated with in-hospital functional recovery in three logistic regression models that in addition to lacunar syndromes, included demographic variables, cardiovascular risk factors, and clinical variables [odds ratio (OR) 2.56], neuroimaging findings (OR 2.48), and outcome data (OR 2.39), respectively. Clinical factors related to severity of infarction available at stroke onset have a predominant influence upon in-hospital outcome and may help clinicians to assess prognosis more accurately. Our work gives a contribution into prognostic factors after acute ischemic stroke. With regard to patterns of stroke, dysarthria-clumsy hand syndrome was a significant predictor of spontaneous in-hospital recovery in ischemic stroke patients.     

Localized increase of GABA levels in brain areas of the rat and inhibition of the plasma LH rise following orchidectomy

Previous studies have suggested that gamma-aminobutyric acid (GABA) exerts inhibitory actions on luteinizing hormone (LH) secretion that are likely to be mediated by modifications in noradrenergic transmission. To explore further this hypothesis we have studied the effect of increasing GABA contents in discrete areas of the brain on plasma LH levels in short-term orchidectomized rats. GABA accumulation was produced by the GABA transaminase inhibitor, gamma-vinyl-GABA (GVG). The locus coeruleus area (LC), where the noradrenaline (NA) cells projecting through the dorsal noradrenergic bundle are located, and several hypothalamic areas that are innervated by NA-containing fibers were microinjected with GVG. Most of these areas are known to be related to the neural control of LH secretion. GVG microinjected in the LC and medial preoptic area increased the GABA content and blunted significantly the acute increase of plasma LH produced by castration. Bicuculline prevented these effects. Delayed effects of GVG were observed when applied in the anterior hypothalamic area and ventromedial-arcuate nucleus area. In these latter areas, a single injection of GVG did not augment the GABA concentrations and was unable to prevent LH release, but a clear inhibitory effect took place after a second injection of GVG between 24 and 48 h after orchidectomy. Unresponsive areas to GVG treatment were the lateral preoptic area, the median eminence and the dorsal raphe. These results add support to the view that GABA inhibits LH release in rats, at discrete areas of the brain.     

Mutation analysis of the SDHD gene in four kindreds with familial paraganglioma: description of one novel germline mutation.

The familial paraganglioma syndrome is an autosomal dominant disorder characterized by the presence of carotid body paragangliomas and, less frequently, paragangliomas of the glomus jugulare, glomus vagale, and adrenal pheochromocytomas. Germline mutations of the genes for succinate dehydrogenase subunits D, B, or C (SDHD, SDHB, SDHC) have been identified in some kindreds with familial paraganglioma. In this study, we report the clinicopathologic features of four different kindreds with familial paraganglioma, which were screened for germline mutations in the SDHD gene. DNA was obtained from tumor and normal tissue, as well as from peripheral blood. Mutation analysis was performed by single-strand conformation polymorphism analysis and DNA sequencing. SDHD germline mutations were detected in the affected family members of the four families, as well as in several asymptomatic carriers. An identical mutation in exon 4 of SDHD (334-337delACTG) was identified in two apparently unrelated kindreds. The third family showed a germline mutation in exon 2 (W43X). The mutations present in these three families had been previously described in Spanish families, suggesting a founder effect. The fourth family exhibited a mutation in exon 2 of SDHD (170-171delTT), which had not been previously identified. The affected family members of the four kindreds showed paragangliomas, located in the head and neck region, and all of them were benign. These results confirm that genetic testing of SDHD may be a powerful tool for the identification of the syndrome in patients with multiple or bilateral paragangliomas.     

External quality control assessment in PCR diagnostics of dengue virus infections

BACKGROUND: Increased travelling to countries endemic for dengue fever (DF) demands efficient laboratory diagnostics. Nucleic acid amplification techniques (NAT) are now frequently used for rapid diagnosis of imported viral diseases. Different PCR systems are available. OBJECTIVES: In order to assess the quality of molecular diagnostics of dengue virus infections, an external quality assurance (EQA) in PCR diagnostics was conducted. Study design: A panel of 10 human plasma samples was prepared and spiked with dengue virus types DEN-1 to DEN-4. In addition, a 10-fold dilution series (1:10-1:10(4) ) of DEN-3 virus was included. The panel was pre-tested by nested RT-PCR, in-house real-time PCR, and a commercial real-time PCR kit. The samples were inactivated by gamma irradiation and shipped in freeze dried state. Thirteen laboratories, within the European network for the diagnostics of imported viral diseases (ENIVD) took part using either single-round, nested, or real-time RT-PCR methods. Two laboratories used two methods in parallel, summarising up to 15 comparable results. RESULTS: 33-100% correct results were achieved. All laboratories detected DEN-2 correctly, followed by DEN-1 (14 positive results of 15), DEN-3 (12/15) and DEN-4 (11/15). Testing of the serial dilution revealed low sensitivity in many labs, with results ranging from 33 to 80% of correctly tested samples. CONCLUSION: The EQA gives a feedback of the quality of the RT-PCR system used by each respective laboratory. The different test systems and amplification conditions demonstrate the importance of external quality control measures.     

The pleiotropic functions of peroxisome proliferator-activated receptor γ

Peroxisome proliferator-activated receptors (PPARs) are nuclear hormone receptors, initially described as molecular targets for synthetic compounds that induce peroxisome proliferation. PPARgamma is the best characterized of the PPARs. The heterodimer of PPARgamma with the retinoid X receptor (RXR) plays a crucial role in adipogenesis and insulin sensitization. The RXR/PPARgamma heterodimer furthermore has been reported to have important immunomodulatory activities and to affect cell proliferation/differentiation pathways in various malignancies. PPARgamma is activated by a number of naturally occurring fatty acid derivatives and by several synthetic compounds, including the thiazolidinediones and L-tyrosine-based insulin sensitizers. This review gives an overview of the pleiotropic functions of PPARgamma and discusses the wide-ranging medical implications that modulation of PPARgamma activity might have for various diseases, ranging from obesity and type 2 diabetes to cancer and inflammation.     

From surnames to the history of Y chromosomes: the Sardinian population as a paradigm

A total of 202 Sardinian male subjects were examined for 13 biallelic stable markers, the complex 49a,f/TaqI system and three microsatellites of the Y chromosome in order to investigate, through surname analysis, on a possible territorial heterogeneity inside the island. The study of geographical distribution and linguistic derivation of Sardinian surnames allow us to discover their 'probable place of origin' and reconstruct ancient genetic isolates which borders are, today, no more recognizable. The molecular analysis revealed that about 90% of the Sardinian Y chromosomes fell into haplogroups E-M35, G-M201, I-M26, J-12f2 and R-M269. In contrast with the territorial homogeneity of these haplogroups, when the individuals were distributed according to their birthplace, a significant difference between the three historically and culturally distinct geographical areas into which Sardinia can be subdivided was observed when the individuals were distributed according to the ancestral location of surnames. In particular, the major contribution to this heterogeneity is due to the 'Sardinian-specific' haplogroup I-M26 (almost completely associated with the 49a,f-Ht12/12f2-10Kb/YCAIIa-21/YCAIIb-11 compound haplotype), which shows both a significantly higher incidence in the central-eastern (archaic) area and a significantly lower frequency in the northern area. The results of this study agree with the hypothesis that the ancestral homeland of this specific subset of haplogroup I is the mountainous central-eastern area of Sardinia, where the population underwent a long history of isolation since ancient times, and highlight the informative power of the surname analysis.