Femoral rollback after cruciate-retaining and stabilizing total knee arthroplasty

Limited data comparing the kinematics of posterior cruciate ligament-retaining or substituting total knee arthroplasty with its own intact knee under identical loadings is available. In the current study, posterior femoral translation of the lateral and medial femoral condyles under unloaded conditions was examined for intact, cruciate-retaining, cruciate ligament-deficient cruciate-retaining and posterior-substituting knee arthroplasties. Cruciate-retaining and substituting total knee arthroplasties behaved similarly to the cruciate-deficient cruciate-retaining total knee arthroplasty between 0 degrees and 30 degrees flexion. Beyond 30 degrees, the posterior cruciate-retaining arthroplasty showed a significant increase in posterior translation of both femoral condyles. The posterior cruciate-substituting arthroplasty only showed a significant increase in posterior femoral translation after 90 degrees. At 120 degrees, both arthroplasties restored approximately 80% of that of the native knee. Posterior translation of the lateral femoral condyle was greater than that observed in the medial condyle for all knees, indicating the presence of internal tibial rotation during knee flexion. The data showed that the posterior cruciate ligament is an important structure in posterior cruciate-retaining total knee arthroplasty and proper balancing is imperative to the success of the implant. The cam-spine engagement is valuable in restoring posterior femoral translation in posterior cruciate-substituting total knee arthroplasty.     

Optimizing flexion after total knee arthroplasty: advances in prosthetic design

The clinical results with most modern total knee arthroplasty (TKA) designs are highly satisfactory regarding pain relief and improving walking ability. However, one problem that has not been addressed fully by most current designs is the ability to consistently achieve flexion greater than 120 degrees. Although the human knee is capable of flexion of more than 150 degrees, an analysis of the results of contemporary TKA reveals that on average, patients rarely flex beyond 120 degrees. Key factors influencing range of flexion after TKA include preoperative knee motion, surgical technique, prosthetic design, and rehabilitation. The success of any total knee system may in part be linked to its ability to optimally restore normal kinematic function. Some arthroplasty designs currently are available that incorporate modifications aimed at improving range of flexion, but limited data currently are available on their function and potential advantages. Currently, an in vitro experimental model incorporating robotics is being used to investigate the kinematics of the native knee and various TKA designs at flexion angles beyond 120 degrees. This robotic model in conjunction with clinical studies may provide an understanding of the limitations of contemporary knee designs regarding achieving higher degrees of knee flexion. This may lead to the refinement of existing designs and development of newer prostheses that may enhance the range of flexion that is achievable after TKA.     

Advantages of multiple markers and polar body analysis in preimplantation genetic diagnosis for Alagille disease

OBJECTIVE: The development of a preimplantation genetic diagnosis (PGD) protocol for Alagille syndrome (AGS), a rare autosomal dominant disorder with hepatic, cardiac and ophthalmologic involvement. METHODS: We developed a polar body (PB)-based multiplex fluorescent PCR reaction for a female affected with AGS. The protocol included analysis of the Jagged 1 (JAG1) familial mutation and five closely linked highly polymorphic markers (D20S162, D20S901, D20S894, and D20S186). RESULTS: In two cycles of PGD 9 of ten embryos were accurately diagnosed by assessment of first and second PBs, one embryo required additional blastomere biopsy. CONCLUSIONS: This protocol takes advantage of the larger window of opportunity for transfer and the increased accuracy of diagnosis afforded by the combination of PB biopsy and multiple marker analysis. Two cycles resulted in the transfer of two and three mutation-free embryos and a subsequent pregnancy as measured by the rising hCG levels.     

A dual role for interleukin-1 in hippocampal-dependent memory processes

Ample research demonstrates that pathophysiological levels of the pro-inflammatory cytokine interleukin-1 (IL-1) produces detrimental effects on memory functioning. However, recent evidence suggests that IL-1 may be required for the normal physiological regulation of hippocampal-dependent memory. To substantiate the physiological role of IL-1 in learning and memory we examined the induction of IL-1 gene expression following a learning experience, and the effects of IL-1 signaling blockade, by either genetic or pharmacological manipulations, on memory functioning. We show that IL-1 gene expression is induced in the hippocampus 24h following fear-conditioning in wild type mice, but not in two mouse strains with impaired IL-1 signaling. Moreover, we report that mice with transgenic over-expression of IL-1 receptor antagonist restricted to the CNS (IL-1raTG) display impaired hippocampal-dependent and intact hippocampal-independent memory in the water maze and fear-conditioning paradigms. We further demonstrate that continuous administration of IL-1ra via osmotic minipumps during prenatal development disrupt memory performance in adult mice, suggesting that IL-1 plays a critical role not only in the formation of hippocampal-dependent memory but also in normal hippocampal development. Finally, we tested the dual role of IL-1 in memory by intracerebroventricular (ICV) administration of different doses of IL-1beta and IL-1ra following learning, providing the first systematic evidence that the involvement of IL-1 in hippocampal-dependent memory follows an inverted U-shaped pattern, i.e., a slight increase in brain IL-1 levels can improve memory, whereas any deviation from the physiological range, either by excess elevation in IL-1 levels or by blockade of IL-1 signaling, results in impaired memory.     

BRCA1 germline mutations in women with uterine serous papillary carcinoma

OBJECTIVE: To determine the possible effects and incidence of BRCA1 and BRCA2 germline mutations in uterine serous papillary carcinoma. METHODS: We screened DNA from 12 women with uterine serous papillary carcinoma for BRCA1 and BRCA2 germline mutations common in the Jewish population (BRCA1-185delAG and 5382insC, BRCA2-6174delT). In women with germline mutations, tumor DNA was screened for loss of heterozygosity at the appropriate loci. RESULTS: Nine women were of Jewish Ashkenazi origin and three were non-Ashkenazi. Two of nine Ashkenazi women were carriers of germline mutations: one 185delAG mutation and one 5382insC mutation. Five women had histories of breast carcinoma before diagnosis of uterine serous papillary carcinoma. Family histories of seven women had at least one first-degree relative with malignant disease. Of those, four had at least one first-degree relative with breast, ovarian, or colon carcinoma. Both carriers had strong family histories of breast-ovarian carcinoma. Loss of heterozygosity analysis found loss of the wild-type BRCA1 allele in the primary uterine tumors. CONCLUSION: BRCA1 germline mutations were observed in two of nine of the women in this series. The loss of heterozygosity in the tumor tissue of the carriers, coupled with the high frequency of family and patient histories of breast or ovarian malignancies, suggest that uterine serous papillary carcinoma might be a manifestation of familial breast-ovarian cancer.     

Treating women with perinatal mood and anxiety disorders (PMADs) with a hybrid cognitive behavioural and art therapy treatment (CB-ART)

This paper presents an overview of a combined, evaluated protocol, cognitive behavioural and art therapy treatment (CB-ART), for the treatment of women with perinatal mood and anxiety disorders (PMADs). The protocol integrates cognitive behavioural interventions and art therapy. CB-ART focuses on changing distressing image, symptom or memory (ISM) that interferes with functioning. The method directs clients to identify compositional elements that characterize their stressful ISM and to alter the element in their imagination, in bodily sensations and on the page. Examples are provided to illustrate the therapeutic process.

     

Genomic analysis of inherited breast cancer among Palestinian women: Genetic heterogeneity and a founder mutation in TP53

Breast cancer among Palestinian women has lower incidence than in Europe or North America, yet is very frequently familial. We studied genetic causes of this familial clustering in a consecutive hospital‐based series of 875 Palestinian patients with invasive breast cancer, including 453 women with diagnosis by age 40, or with breast or ovarian cancer in a mother, sister, grandmother or aunt (“discovery series”); and 422 women diagnosed after age 40 and with negative family history (“older‐onset sporadic patient series”). Genomic DNA from women in the discovery series was sequenced for all known breast cancer genes, revealing a pathogenic mutation in 13% (61/453) of patients. These mutations were screened in all patients and in 300 Palestinian female controls, revealing 1.0% (4/422) carriers among older, nonfamilial patients and two carriers among controls. The mutational spectrum was highly heterogeneous, including pathogenic mutations in 11 different genes: BRCA1, BRCA2, TP53, ATM, CHEK2, BARD1, BRIP1, PALB2, MRE11A, PTEN and XRCC2. BRCA1 carriers were significantly more likely than other patients to have triple negative tumors (p = 0.03). The single most frequent mutation was TP53 p.R181C, which was significantly enriched in the discovery series compared to controls (p = 0.01) and was responsible for 15% of breast cancers among young onset or familial patients. TP53 p.R181C predisposed specifically to breast cancer with incomplete penetrance, and not to other Li‐Fraumeni cancers. Palestinian women with young onset or familial breast cancer and their families would benefit from genetic analysis and counseling.     

Cancer risks among BRCA1 and BRCA2 mutation carriers

BRCA1 and BRCA2 mutations increase breast and ovarian cancer risks substantially enough to warrant risk reduction surgery, despite variable risk estimates. Underlying this variability are methodological issues, and also complex genetic and nongenetic effects. Although many modifying factors are unidentified, known factors can already be incorporated in individualised risk prediction.     

Apolipoprotein E genotypes and age of onset in early-onset familial Alzheimer's disease

The effect of the apolipoprotein E (APOE) ?4 allele on age of onset was analyzed in two groups of families with early-onset Alzheimer's disease (AD), (1) Volga German (VG) kindreds, in which AD is caused by an unknown locus and (2) early-onset non-VG families showing evidence of linkage to chromosome 14. The ?4 allele did not have a detectable effect on age of onset in either group. This finding suggests some forms of early-onset familial AD are not modifiable by APOE status, or that AD can be caused by APOE-independent pathways.     

Amyloid (Aβ) deposition in chromosome 1–linked Alzheimer's disease: The volga german families

Amyloid β protein (Aβ) deposition was investigated in the frontal cortex of 6 cases of (genetically confirmed) chromosome 1–linked Alzheimer's disease (AD) (PS-2 gene mutation) among the Volga German families using the end-specific monoclonal antibodies BA27 and BC05 to detect the presence of Aβ₄₀ and Aβ₄₂₍₄₃₎, respectively. In all patients, Aβ₄₂₍₄₃₎ was the predominant peptide species present, although the total amount of Aβ₄₀ and Aβ₄₂₍₄₃₎ deposited in plaques did not differ from that seen in sporadic AD and was significantly lower than that occurring in AD due to PS-1 gene mutations. Therefore, mutations in the PS-2 gene, like those in the presenilin-1 (PS-1) and amyloid precursor protein (APP) genes, are associated with an initial and preferential deposition of Aβ₄₂₍₄₃₎ within the brain. Although the mechanisms(s) whereby the PS-1 and PS-2 gene mutations operate remains unclear, it seems from the present study that the effect of the PS-2 gene mutation on the brain is muuch less severe, at least as far as Aβ deposition is concerned, than that of the PS-1 mutation, which seems to confer a much earlier and a much more aggressive development of AD.