Type of Hip Fracture in Patients With Parkinson Disease is Associated With Femoral Bone Mineral Density

Di Monaco M, Vallero F, Di Monaco R, Tappero R, Cavanna A. Type of hip fracture in patients with Parkinson disease is associated with femoral bone mineral density.

Objective

To investigate the association between bone mineral density (BMD) and hip fracture type (cervical or trochanteric) in a sample of fallers with Parkinson disease (PD).

Design

Observational study.

Setting

Rehabilitation hospital in Italy.

Patients

We investigated 1040 of 1120 white fallers consecutively admitted to a rehabilitation hospital for hip fracture. Thirty-eight (3.65%) of the 1040 patients suffered from PD secondarily. Thirty-eight controls matched for sex, age, and hip fracture type were found among the 1002 non-PD fallers.

Interventions

Not applicable.

Main Outcome Measures

BMD was assessed by dual-energy x-ray absorptiometry at a mean ± SD of 21.9±7.5 days after fracture occurrence in the 38 PD patients and 21.6±5.9 days after fracture occurrence in the 38 controls.

Results

BMD assessed at total femur, trochanter, and intertrochanteric region was significantly lower in the 15 PD patients with trochanteric fractures than in the 23 with cervical fractures; the mean T score differences were 0.57 (95% confidence interval [CI], 0.07–1.08; P=.028), 0.66 (95% CI, 0.04–1.28; P=.037), and 0.63 (95% CI, 0.11–1.15; P=.019), respectively. A significant association between femoral BMD and hip fracture type was found at logistic regression after adjustment for several confounders. Results in the 38 controls were similar to those obtained in the 38 PD fallers.

Conclusions

In a sample of PD fallers as in a control group of non-PD fallers, BMD levels assessed at 3 femoral sites were significantly lower in the patients who sustained trochanteric fractures than in those with cervical fractures of the hip.     

Differential effect of ganglioside GM1 on rat brain phosphoproteins: potentiation and inhibition of protein phosphorylation regulated by calcium/calmodulin and calcium/phospholipid-dependent protein kinases

The monosialoganglioside GM1 displays complex effects on protein phosphorylation of rat cerebral cortex membrane preparations. The exogenous ganglioside at a concentration of 350 microM in absence of calcium only stimulated the phosphorylation of a protein of MW = 64,000. In presence of 1 mM calcium a twofold effect is observed irrespective of the phosphoprotein considered. In particular there is an enhancement of 32P incorporation in four major phosphoproteins of MW = 160,000, 140,000, 64,000 and 50,000 in presence of GM1 compared with that observed with calcium alone. The maximal stimulating effect is achieved with a ganglioside concentration of 35 microM. This effect is inhibited by the addition of 100 microM trifluoperazine (TFP), a phenothiazine known to inhibit calmodulin and protein kinase-C activities. These four proteins represent the major substrates for the calcium/calmodulin-dependent protein kinase with the MW = 64,000 and 50,000 proteins co-migrating with the autophosphorylated subunits of this enzyme. In addition, the ganglioside inhibited the phosphorylation of three proteins with MW = 86,000, 20,000 and 14,000. The electrophoretic properties of these phosphoproteins are similar to the autophosphorylated form of protein kinase-C and to the rat myelin basic proteins, respectively. The effect of the ganglioside on their phosphorylation is not influenced by TFP. Finally, a protein with an apparent molecular weight of 46,000 shows also an increased phosphorylation in presence of GM1. The reported results indicate that exogenous GM1 can have profound effects on different kinases such as the calcium/calmodulin dependent protein kinase, the protein kinase-C and also some unknown calcium-independent protein kinases.     

Efficacy of low-dose rituximab for mixed cryoglobulinemia

Rituximab at 375 mg/m(2) x 4 is effective for refractory HCV-related mixed cryoglobulinemia. We conducted a pilot study to assess the efficacy of a lower dosage, 250 mg/m(2) x 2. Six consecutive patients with mixed cryoglobulinemia were treated. All patients had severe or life-threatening disease manifestations, including necrotizing skin ulcers, renal disease, hyperviscosity or intestinal vasculitis. Four of five evaluable patients (excluding one early death) had >80% decrease of cryocrit and remission of vasculitis at the end of a 22- to 55-week (median 40) follow-up. The non-responder failed to respond to additional rituximab treatment, suggesting intrinsic resistance rather than insufficient dosage as the cause of treatment failure. No sustained increase of HCV viremia after rituximab was observed. Rituximab at 250 mg/m(2) x 2 may be as effective as at 375 mg/m(2) x 4 for treating mixed cryoglobulinemia. Larger studies are required to assess the efficacy of low-dose rituximab.     

FINGERPRINTING OF HLA CLASS I GENES FOR IMPROVED SELECTION OF UNRELATED BONE MARROW DONORS

The degree of matching of HLA genes between the selected donor and recipient is an important aspect of the selection of unrelated donors for allogeneic bone marrow transplantation (UBMT). The most sensitive methods currently used are serological typing of HLA class I genes, mixed lymphocyte culture (MLC), IEF and molecular genotyping of HLA class II genes by direct sequencing of PCR products. Serological typing of class I antigenes (A, B and C) fails to detect minor differences demonstrated by direct sequencing of DNA polymorphic regions. Molecular genotyping of HLA class I genes by DNA analysis is costly and work-intensive. To improve compatibility between donor and recipient, we have set up a new rapid and non-radioisotopic application of the ‘fingerprinting PCR’ technique for the analysis of the polymorphic second exon of the HLA class I A, B and C genes. This technique is based on the formation of specific patterns (PCR fingerprints) of homoduplexes and heterodu-plexes between heterologous amplified DNA sequences. After an electrophoretic run on non-denaturing polyacrylamide gel, different HLA class I types give allele-specific banding patterns. HLA class I matching is performed, after the gel has been soaked in ethidium bromide or silver-stained, by visual comparison of patients’ fingerprints with those of donors. Identity can be confirmed by mixing donor and recipient DNAs in an amplification cross-match. To assess the technique, 10 normal samples, 22 related allogeneic bone marrow transplanted pairs and 10 unrelated HLA-A and HLA-B serologically matched patient-donor pairs were analysed for HLA class I polymorphic regions. In all the related pairs and in 1/10 unrelated pairs, matched donor-recipient patterns were identified. This new application of PCR fingerprinting may confirm the HLA class I serological selection of unrelated marrow donors.     

Low levels of 25-hydroxyvitamin D are associated with the occurrence of concomitant upper limb fractures in older women who sustain a fall-related fracture of the hip

Objective

To investigate the association between serum levels of 25-hydroxyvitamin D and the occurrence of simultaneous fractures of the upper limb in older women who sustain a fall-related fracture of the hip.

Study design

Cross-sectional study.

Main outcome measures

We investigated 472 of 480 white women consecutively admitted to a rehabilitation hospital because of a fall-related hip fracture. Twenty-seven (5.7%) of the 472 women sustained a concomitant upper-limb fracture of either distal radius (20 women) or proximal humerus (seven women). We assessed serum levels of 25-hydroxyvitamin D 14.2 ± 4.1 (mean ± SD) days after surgical repair of the hip fracture in the 472 women by an immunoenzymatic assay.

Results

Twenty-five-hydroxyvitamin D levels were significantly lower in the 27 women with concomitant fractures of both hip and upper limb than in the remaining 445 hip-fracture women: mean ± SD values were 6.5 ± 5.0 ng/ml and 11.7 ± 10.4 ng/ml respectively in the two groups (mean difference between groups 5.2 ng/ml: 95% CI 1.2–9.2; p = 0.011). Low levels of 25-hydroxyvitaimn D were significantly associated with concomitant fractures of the upper limb (p = 0.017), after adjustment for eight potential confounders including age, height, weight, hip-fracture type, cognitive impairment, neurologic impairment, previous hip fracture, and previous upper-limb fracture.

Conclusions

Low levels of 25-hydroxyvitamin D were significantly associated with concomitant upper-limb fractures in our sample of older women with a fall-related fracture of the hip. Preventing vitamin D deficiency may lower the incidence of simultaneous fractures due to a singe fall in elderly women.     

Polarized secretion of lysosomes at the B cell synapse couples antigen extraction to processing and presentation

Engagement of the B cell receptor (BCR) by surface-tethered antigens (Ag) leads to formation of?a synapse that promotes Ag uptake for presentation onto major histocompatibility complex class II (MHCII) molecules. We have highlighted the membrane trafficking events and associated molecular mechanisms involved in Ag extraction and processing at the B cell synapse. MHCII-containing lysosomes are recruited to the synapse where they locally undergo exocytosis, allowing synapse acidification and the extracellular release of hydrolases that promote the extraction of the immobilized Ag. Lysosome recruitment and secretion results from the polarization of the microtubule-organizing center (MTOC), which relies on the cell division cycle (Cdc42)-downstream effector, atypical protein kinase C (aPKCζ). aPKCζ is phosphorylated upon BCR engagement, associates to lysosomal vesicles, and is required for their polarized secretion at the B cell synapse. Regulation of B lymphocyte polarity therefore emerges as?a central mechanism that couples Ag extraction to Ag processing and presentation.     

An overview on the genetic of rheumatoid arthritis: a never-ending story

Rheumatoid arthritis (RA) is a chronic, systemic, inflammatory, multi-factorial disease sustained by environmental and genetic factors. These seem to be necessary but not sufficient in the disease development, nonetheless they can be responsible of different clinical pictures and response to therapy, and they can represent potential therapeutic targets. Several genes have been indicated so far in the pathogenesis of RA. The most important region is the Human Leukocyte Antigen (HLA) that contributes to approximately half of the genetic susceptibility for RA. The association seems to be stronger or specific for anti-citrullinated protein antibodies positive disease. Several alleles in the epitope-recognition part of the HLA molecule that show the highest association with RA susceptibility, also share a common string of amminoacid residues (the so-called shared-epitope hypothesis). Other variants in potentially pathogenic genes located in non-MHC regions have been implicated by recently performed genome wide analysis studies. These genes include PTPN22, TRAF1-C5, PADI4, STAT4. Other polymorphisms seem to be responsible for more aggressive disease phenotype such as those located at TNF, IL-1, IL-6, IL-4, IL-5, OPN, PRF1. However, still nowadays, the genetic background of RA remains to be clearly depicted, and the efforts in the post-genomic era can bring to an estimation of the real likelihood of the genetic effect on RA. Finally, the discovery of new genes associated with the disease can be relevant in finding potential biomarkers, potentially useful in disease diagnosis and treatment.     

Comparative evaluation of different DNA extraction methods for HPV genotyping by linear array and INNO-LiPA

In order to investigate the influence of DNA extraction on two PCR-based HPV genotyping tests (Linear Array, Roche and INNO-LiPA Extra, Innogenetics), three different procedures were used to purify DNA from 28 cervico-vaginal samples tested previously by the Hybrid Capture 2: the AmpliLute Liquid Media Extraction kit (Roche), the QIAamp DNA Blood mini kit (QIAGEN), and the NucliSENS EasyMAG automated platform (bioMérieux). All HC2-positive samples were found positive by both assays, independently of the extract used. Type-specific concordance (i.e., identical HPV type-specific profile in all the extracts of the same sample) was observed in 55% and 75% of the cases testing samples by the Linear Array and the INNO-LiPA, respectively. Using the DNA extracted with the two manual methods the results were concordant in 75% of the cases both for the Linear Array and the INNO-LiPA. When comparing the Linear Array results obtained on either of the two manual extracts with those obtained following automated extraction, 65% of the samples showed type-specific concordance in both cases. The INNO-LiPA results were concordant in 80% of the cases comparing the AmpliLute versus the automated extract, while concordant results were observed in 90% of the cases when comparing the QIAGEN versus the automated extract. In conclusion, the Linear Array and INNO-LiPA results are affected by the method of DNA extraction. Consequently, different HPV type-specific profiles may be observed using different extracts of the same sample. The use of consistent protocols for DNA purification is a priority to guarantee intra-assay reproducibility over time.