Large diaphyseal-incorporating allograft prosthetic composites: when, how, and why : Treatment of advanced proximal humeral bone loss.

BACKGROUND: Proximal humeral bone loss in shoulder arthroplasty is a complex problem with a heterogeneous presentation. Different etiologies may contribute to varying degrees of severity in bone loss that dictate different treatment approaches. OBJECTIVES: The purpose of this is article is to describe our technique for treatment of proximal humeral bone loss with proximal humeral allograft prosthetic composites (APC) and identify factors that may predict when larger allografts may be necessary. MATERIALS AND METHODS: Ninety-nine patients were identified that had undergone reverse total shoulder arthroplasty with use of a proximal humeral allograft. Thirty-nine of these had large allografts that involved a significant portion of the diaphysis. Preoperative characteristics were examined to identify factors that may be associated with use of a larger diaphyseal-incorporating allograft. RESULTS: Well-fixed humeral stems could be treated with short metaphyseal allografts in 55 of 65 (85%) cases. Loose stems required longer diaphyseal-incorporating allografts in 28 of 31 (90%) cases, and these were commonly associated with periprosthetic fractures (n = 10), failed prior APC (n = 6), and infection (n = 5). Noncemented stems required diaphyseal grafts in 75% of cases, compared to cemented stems which required larger grafts in 34% of cases. CONCLUSIONS: Proximal humeral bone loss in the setting of revision shoulder arthroplasty can be successfully managed with a reverse total shoulder and proximal humeral allograft. Larger allografts are frequently required for loose humeral stems, and noncemented stems appear more likely to require larger allografts than cemented stems.

Multimodal imaging in systemic lupus erythematosus patients with diffuse neuropsychiatric involvement.

OBJECTIVES: The objective of this paper is to investigate conventional and nonconventional brain magnetic resonance imaging (MRI) findings in systemic lupus erythematosus (SLE) patients with diffuse neuropsychiatric involvement (dNPSLE) compared to healthy controls (HCs). METHODS: Twenty-six (26) SLE patients with one or more diffuse NP syndromes related to the central nervous system (CNS) (dNPSLE) and 36 age- and sex-matched HCs were scanned on a 3T MRI using a multimodal imaging approach. Univariate and multivariate analyses were used to determine MRI-specific measure differences between dNPSLE and HCs for lesion burden, tissue-specific atrophy, magnetization transfer ratio (MTR) and diffusion-tensor imaging (DTI) outcomes. RESULTS: In univariate analyses, dNPSLE patients showed significantly increased T1 lesion number (p = .001) and T1-lesion volume (LV, p = .008) compared to HCs. dNPSLE patients showed decreased whole brain volume (p < .0001), gray matter volume (p < .0001), cortical volume (p < .0001) and increased lateral ventricle volume (p = .004) compared to HCs. dNPSLE patients had increased axial diffusivity (AD) of NAWM (p = .008) and NA brain tissue (p = .017) compared to HCs. In the multivariate regression analysis, decreased cortical volume was associated with SLE (R (2) = 0.59, p < .0001). CONCLUSIONS: This study shows that cortical and central atrophy are associated with SLE patients with diffuse CNS syndromes. Microscopic tissue injury in the NAWM on AD DTI measures in SLE patients indicates a predominant reduction of axonal density.

CSF dynamics and brain volume in multiple sclerosis are associated with extracranial venous flow anomalies: a pilot study.

AIM: We previously reported unexpectedly robust associations between vascular haemodynamic (VH) anomalies in the principal extracranial cerebral veins, causing chronic cerebrospinal venous insufficiency (CCSVI), and multiple sclerosis (MS). Aim of this study was to investigate the relationship between the VH changes and MRI measures of MS disease severity in a cross sectional survey. METHODS: The number of anomalous VH criteria were measured using an echo-color Doppler, whereas CSF flow, atrophy and lesion measures were obtained from quantitative magnetic resonance imaging (MRI) analysis in sixteen consecutive relapsing-remitting MS patients, (mean age: 36.1+/-SD 7.3 years, disease duration: 7.5+/-1.9 years and median EDSS: 2.5) and in 8 healthy controls (HC) with similar age and sex distributions. RESULTS: All 16 MS patients investigated and none of the HCs met the VH criteria for CCSVI (P<0.0001). MS patients showed significantly lower net CSF flow compared to the HC (P=0.038) that was associated with number of anomalous VH criteria present (r=0.79, P<0.001). Moreover, increases in the number of anomalous VH criteria present were negatively associated with lower whole brain volume (Spearman R=-0.5, P=0.05). CONCLUSION: VH changes occur more frequently in MS patients than controls. Altered VH is associated with abnormal CSF flow dynamics and decreased brain volume.

Apolipoprotein E ε4-positive multiple sclerosis patients develop more gray-matter and whole-brain atrophy: a 15-year disease history model based on a 4-year longitudinal study.

Multiple sclerosis is a disease with considerable individual variation, and genetic background plays a key role in disease susceptibility and severity. The objective of the study was to evaluate the relationship between apolipoprotein E (APOE) genotype and the evolution of different clinical and MRI parameters. We investigated a group of 150 relapsingremitting patients that completed 4-year follow-up. The mean age was 30.2 years, disease duration 56.8 months, and baseline Expanded Disability Status Scale (EDSS) 1.8. The changes in brain parenchymal volume (BPV), gray matter (GMV), white matter (WMV) and peripheral gray volume (PGMV) were measured by SIENA/X. T2-lesion volume was assessed by semi-automated methods. The mixed-effect model analysis was used to investigate evolution of clinical and MRI parameters in relation to the APOE ε4 genotype considering two different time models: 4-year follow-up and 15-year period from disease onset. We identified 36 APOE ε4-positive patients. Decline of GMV (P = 0.017), and BPV (P = 0.029) were significantly faster in APOE ε4-positive than in APOE ε4-negative patients in the 15-year model. In the 4- year model, a trend for faster decrease of GMV was found in APOE ε4-positive patients (P = 0.067). No differences in other MRI parameters or EDSS were found between the APOE groups. The results of the study suggest that APOE ε4-positive patients experience faster rate of gray matter atrophy.

The severity of chronic cerebrospinal venous insufficiency in patients with multiple sclerosis is related to altered cerebrospinal fluid dynamics.

Chronic cerebrospinal venous insufficiency (CCSVI) is a vascular picture that shows a strong association with multiple sclerosis (MS). The aim of this study was to investigate the relationship between a Doppler cerebral venous hemodynamic insufficiency severity score (VHISS) and cerebrospinal fluid (CSF) flow dynamics in 16 patients presenting with CCSVI and relapsing-remitting MS (CCSVI-MS) and in eight healthy controls (HCs). The two groups (patients and controls) were evaluated using validated echo-Doppler and advanced 3T-MRI CSF flow measures. Compared with the HCs, the CCSVI-MS patients showed a significantly lower net CSF flow (p=0.027) which was highly associated with the VHISS (r=0.8280, r2=0.6855; p=0.0001). This study demonstrates that venous outflow disturbances in the form of CCSVI significantly impact on CSF pathophysiology in patients with MS.

Magnetic resonance imaging characteristics of children and adults with paediatric-onset multiple sclerosis.

The purpose of this study was to compare the clinical and quantitative magnetic resonance imaging metrics of paediatric-onset multiple sclerosis to adult-onset multiple sclerosis. It was a prospective comparison of clinical and magnetic resonance imaging characteristics of two paediatric onset multiple sclerosis and two adult onset multiple sclerosis groups that were matched for disease duration. The paediatric-onset-C group consisted of children with paediatric-onset multiple sclerosis with mean disease duration of 2.7 years, whereas the paediatric onset-A group consisted of adults with mean disease duration of 20 years. The adult onset multiple sclerosis-1 and adult onset multiple sclerosis-2 groups were matched to the paediatric onset-C and paediatric onset-A groups. The brain magnetic resonance imaging measures included: T(1)-, T(2)- and gadolinium contrast-enhancing volumes and the T(2)-lesion volume relative magnetization transfer ratio, global and tissue specific white and grey matter brain atrophy and normal appearing grey and white matter magnetization transfer ratio. Regression analyses were employed for magnetic resonance imaging measures. The paediatric onset multiple sclerosis-C (n = 17) and adult onset multiple sclerosis-1 (n = 81) groups had mean disease duration values of 2.7 +/- standard deviation 2.0 and 2.6 +/- 1.1 years, respectively. The paediatric onset multiple sclerosis-A group (n = 33) and adult onset multiple sclerosis-2 group (n = 300) had mean disease durations of 20 +/- standard deviation 10.9 and 20 +/- 9.3 years, respectively. In regression analysis, the T(2)- lesion volume of the paediatric onset multiple sclerosis-C and adult onset multiple sclerosis-1 groups were similar but there was a trend toward higher T(1)- lesion volume (P = 0.028) in the paediatric onset group. The brain parenchymal fraction and grey matter fraction in the paediatric-onset multiple sclerosis-C group were higher than those for the adult onset multiple sclerosis-1 group (both P < 0.001). The frequency of progressive multiple sclerosis in the paediatric onset multiple sclerosis-A group (27.3%) trended lower (odds ratio = 0.43, P = 0.042) than that in the adult onset multiple sclerosis-2 group (46.3%). The Expanded Disability Status Scale (median; inter-quartile range) in the paediatric onset multiple sclerosis-A group (2.25; 2.5) trended lower (P = 0.058) compared with the adult onset multiple sclerosis-2 group (3.5; 4.0). There was a trend toward lower magnetization transfer ratio values in T(2)-lesions, normal appearing grey matter and normal appearing white matter and higher grey matter fraction in the paediatric onset multiple sclerosis-A group compared with the adult onset multiple sclerosis-2 group. There was no evidence for differences on T(2)-lesion volume, T(1)-lesion volume, brain parenchymal fraction or white matter fraction. Paediatric-onset multiple sclerosis is characterized by a significant disease burden both early and later in the disease course. Despite this, disability is slower to accrue in paediatric onset multiple sclerosis than adult onset multiple sclerosis.

Randomized study of interferon beta-1a, low-dose azathioprine, and low-dose corticosteroids in multiple sclerosis.

BACKGROUND: Studies evaluating interferon beta (IFNbeta) for multiple sclerosis (MS) showed only partial efficacy. In many patients, IFNbeta does not halt relapses or disability progression. One strategy to potentially enhance efficacy is to combine IFNbeta with classical immunosuppressive agents, such as azathioprine (AZA) or corticosteroids, commonly used for other autoimmune disorders. OBJECTIVE: The Avonex-Steroids-Azathioprine study was placebo-controlled trial and evaluated efficacy of IFNbeta-1a alone and combined with low-dose AZA alone or low-dose AZA and low-dose corticosteroids as initial therapy. METHODS: A total of 181 patients with relapsing-remitting MS (RRMS) were randomized to receive IFNbeta-1a 30 microg intramuscularly (IM) once weekly, IFNbeta-1a 30 microg IM once weekly plus AZA 50 mg orally once daily, or IFNbeta-1a 30 microg IM once weekly plus AZA 50 mg orally once daily plus prednisone 10 mg orally every other day. The primary end point was annualized relapse rate (ARR) at 2 years. Patients were eligible for enrollment in a 3-year extension. RESULTS: At 2 years, adjusted ARR was 1.05 for IFNbeta-1a, 0.91 for IFNbeta-1a plus AZA, and 0.73 for combination. The cumulative probability of sustained disability progression was 16.8% for IFNbeta-1a, 20.7% for IFNbeta-1a plus AZA, and 17.5% for combination. There were no statistically significant differences among groups for either measure at 2 and 5 years. Percent T2 lesion volume change at 2 years was significantly lower for combination (+14.5%) versus IFNbeta-1a alone (+30.3%, P < 0.05). Groups had similar safety profiles. CONCLUSION: In IFNbeta-naïve patients with early active RRMS, combination treatment did not show superiority over IFNbeta-1a monotherapy.

Gender-related differences in MS: a study of conventional and nonconventional MRI measures.

BACKGROUND: Studies showed gender-associated differences in multiple sclerosis (MS) disease evolution and in the evolution of conventional magnetic resonance imaging (MRI) findings. OBJECTIVE: The aim of this study was to investigate gender differences according to a number of conventional and nonconventional MRI measures in patients with MS. METHODS: We examined 763 consecutive patients with MS [499 (19.2% men) relapsing-remitting (RR), 230 (24.8% men) secondary-progressive, and 34 (44.1% men) primary-progressive], 32 (21.9% men) patients with clinically isolated syndrome (CIS), and 101 (30.7% men) normal controls (NC). Patients were assessed using conventional and nonconventional MRI measures. Gender-related MRI differences were investigated using general linear model analysis, corrected for MS disease type. RESULTS: In the total MS group, male patients showed lower normalized peripheral gray matter (GM) (P<0.001) and normalized GM (P=0.011) volumes than female patients. Female patients presented lower normalized white matter (WM) volumes (P=0.011). These gender effects were not observed in NC. Male patients also showed more advanced central atrophy (P=0.022). In RRMS male patients, there was also a higher lateral ventricle volume (P=0.001). The GM-WM normalized ratio was lower for male patients with MS compared with male NC (0.97 vs. 1.09, P<0.001) but not in patients with CIS compared with NC. CONCLUSIONS: There were no significant gender-related differences regarding nonconventional MRI measures. GM and central atrophy are more advanced in male patients, whereas WM atrophy is more advanced in female patients. These gender-related MRI differences may be explained by the effect of sex hormones on brain damage and repair mechanisms.

Evolution of different MRI measures in patients with active relapsing-remitting multiple sclerosis over 2 and 5 years: a case-control study.

BACKGROUND: There is growing evidence for the concept of multiple sclerosis (MS) as an inflammatory neurodegenerative disease, with a different pattern of atrophy evolution in grey matter (GM) and white matter (WM) tissue compartments. OBJECTIVE: We aimed to investigate the evolution of different MRI measures in early relapsing-remitting patients with MS and in normal controls (NCs) over 2 years. We also evaluated the progression of these MRI measures in a subset of patients who were followed for up to 5 years. METHODS: Included in this study were 147 patients who participated in the combination ASA (Avonex Steroids Azathioprine) study and completed full treatment, clinical and MRI assessment at 0, 12 and 24 months. A subgroup of 66 patients was followed for 36 months, 51 patients for 48 months and 43 patients for 60 months. Mean age at baseline was 30.7 years, mean disease duration was 5.5 years, mean EDSS was 1.8 and mean annualised relapse rate before study entry was 1.7. MRI scans were performed on a 1.5T scanner every 2 months for the first 2 years and thereafter once yearly for up to 5 years. In addition to the MS group, 27 NCs were examined at months 0, 12 and 24 using the same MRI protocol. Percentage brain volume change (PBVC), GM volume (GMV), WM volume (WMV) and peripheral grey volume (PGV) were measured annually using SIENA/X software. T2-hyperintense lesion volume (LV), lateral ventricle volume (LVV) and third ventricle width (3VW) were also assessed annually. RESULTS: Over the period of 0-24 months, patients with MS lost significantly more GMV (-2.6% vs -0.72%, p<0.001), PGV (-2.4% vs -1.03%, p<0.001) and PBVC (-1.2% vs -0.22%, p<0.001), and increased in LVV (+16.6% vs +0.55%, p<0.003) and 3VW (+9.3% vs 0%, p = 0.003), when compared with NCs. Within-person change in MRI measures for patients with MS over 5 years was -4.2% for PBVC, -6.2% for GMV, -5.8% for PGV, -0.5% for WMV (all p<0.001), +68.7 for LVV (p<0.001), +4% for 3VW (p<0.001) and +42% for T2-LV (p<0.001). CONCLUSIONS: Our study confirmed a different pattern of GM, WM and central atrophy progression over 2 years between patients with MS and NCs. The study showed a different evolution of tissue compartment atrophy measures in patients with MS, with faster decline in cortical and deep GM regions, as well as periventricular WM regions, over a 5-year period.

Postnatal depression across countries and cultures: a qualitative study.

BACKGROUND: Postnatal depression seems to be a universal condition with similar rates in different countries. However, anthropologists question the cross-cultural equivalence of depression, particularly at a life stage so influenced by cultural factors. AIMS: To develop a qualitative method to explore whether postnatal depression is universally recognised, attributed and described and to enquire into people's perceptions of remedies and services for morbid states of unhappiness within the context of local services. METHOD: The study took place in 15 centres in 11 countries and drew on three groups of informants: focus groups with new mothers, interviews with fathers and grandmothers, and interviews with health professionals. Textual analysis of these three groups was conducted separately in each centre and emergent themes compared across centres. RESULTS: All centres described morbid unhappiness after childbirth comparable to postnatal depression but not all saw this as an illness remediable by health interventions. CONCLUSIONS: Although the findings of this study support the universality of a morbid state of unhappiness following childbirth, they also support concerns about the cross-cultural equivalence of postnatal depression as an illness requiring the intervention of health professionals; this has implications for future research.

Is postnatal depression a risk factor for sudden infant death?

BACKGROUND: In New Zealand, an association has been shown between postnatal depression and sudden infant death syndrome (SIDS). AIM: To replicate the New Zealand study. DESIGN OF STUDY: Case-control study. SETTING: The city of Sheffield, UK. METHOD: The database of the Sheffield Child Development Study was used Demographic and obstetric data were collected and at one month postpartum the Edinburgh Postnatal Depression Scale (EPDS) was administered. Detailed information on the cause of all infant deaths was available. RESULTS: There were 32,984 live births during the study period (from the year 1988 to 1993) and 42 babies died with the cause registered as SIDS. Multivariate analysis showed that smoking was the most important risk factorfor SIDS (odds ratio [OR] = 7.24, 95% confidence interval [95% CI] = 2.76 to 19.01), followed by a high EPDS (OR = 3.20, 95% CI = 1.46 to 6.99) and residence in an area of poverty (OR = 2.33, 95% CI = 1.06 to 5.11). CONCLUSIONS: The Sheffield data confirm the New Zealand findings. A high EPDS score and, by implication, postnatal depression, may be risk factors for SIDS, however, there are many possible explanations for the association.

Changes in the motility of B16F10 melanoma cells induced by alterations in resting calcium influx.

Alterations in the extracellular Ca(2+) or K(+) concentration had significant influences on the motility of B16F10 melanoma cells measured in the absence of exogenous integrins using a conventional Boyden chamber assay. At normal K(+) concentrations, motility increased slightly when the concentration of Ca(2+) was increased 10-fold. At normal Ca(2+) concentrations, motility increased by 290% when the extracellular K(+) concentration was reduced 10-fold (from control of 5.4 mM to 0.54 mM), and increased to 250% of control levels when the K(+) concentration was increased between 30 and 54 mM, but was relatively uninfluenced at K(+) concentrations between 5 and 30 mM. Simultaneous application of low concentrations (20 microM) of GdCl(3) completely prevented the effects of low and high K(+) on motility. Exposure to Gd(3+) or Tb(3+) also produced a flattening of the cells and enhanced cell attachment. Although the steady state intracellular Ca(2+) concentration was not significantly influenced by the K(+) concentration, the resting permeability to divalent cations, determined from Mn(2+) quench rates in fura-loaded cells, was significantly increased by a reduction in the K(+) concentration. These results indicate that resting Ca(2+) influx is critical to the movement of B16F10 melanoma cells, and demonstrate that lanthanides, which block resting Ca(2+) influx pathways, are potent antimotility agents.

The long-term follow-up of women treated for postnatal depression at a specialist day hospital compared to routine primary care.

BACKGROUND: Postnatal depression affects approximately 13% of childbearing women. There are very few specialist treatment centres, despite emerging evidence that these units are superior to routine primary care in the short term. We investigated the long-term benefits of treatment for postnatal depression at a specialist day unit, compared to routine primary care. METHODS: Women who took part in an earlier study of postnatal depression were invited to participate in this follow-up. Self-report questionnaires (the Work, Leisure and Family Life Questionnaire - Modified (WLFQ-M) and the Dyadic Adjustment Scale (DAS)) were administered, together with the revised Clinical Interview Schedule (CIS-R). Information was also obtained regarding subsequent children and depressive episodes since the initial study. RESULTS: Of the original cohort of 60 women, 23 agreed to participate in the follow-up. There were no significant differences between DAS and WLFLQ-M scores or ICD-10 diagnoses of depressive episode between the women who had previously received specialist care. However, the numbers were small and make conclusions difficult. Qualitative analysis suggests that treatment at a specialist unit is beneficial in the long term. CONCLUSION: Further, larger studies of the long-term benefits of specialist treatment need to be carried out. (Int J Psych Clin Pract 2002; 6: 199-203 ).

Differences between perspectives of physicians and patients on anticoagulation in patients with atrial fibrillation: observational study.

OBJECTIVE: To determine and compare physicians' and patients' thresholds for how much reduction in risk of stroke is necessary and how much risk of excess bleeding is acceptable with antithrombotic treatment in people with atrial fibrillation. DESIGN: Prospective observational study. SETTING: Tertiary and peripheral referral centres in Nova Scotia, Canada. PARTICIPANTS: 63 physicians who were treating patients with atrial fibrillation and 61 patients at high risk for atrial fibrillation. MAIN OUTCOME MEASURES: Participants underwent a face to face interview with a probability trade-off tool. Thresholds were determined for the minimum reduction in risk of stroke necessary and the maximum increase in risk of excess bleeding acceptable for treatment with aspirin and warfarin in people with atrial fibrillation. RESULTS: The minimum number of strokes that needed to be prevented in 100 patients over two years for warfarin to be justified was significantly lower for patients than for physicians (1.8 (SD 1.9) v 2.5 (1.6), P=0.009), whereas for aspirin there was no difference between patients and physicians (1.3 (1.3) v 1.6 (1.5), P=0.29). The maximum number of excess bleeds acceptable in 100 patients over two years for use of warfarin and aspirin was significantly higher for patients than for physicians (warfarin 17.4 (7.1) v 10.3 (6.1); aspirin 14.7 (8.5) v 6.7 (6.2); P<0.001 for both comparisons). CONCLUSIONS: Patients at high risk for atrial fibrillation placed more value on the avoidance of stroke and less value on the avoidance of bleeding than did physicians who treat patients with atrial fibrillation. The views of the individual patient should be considered when decisions are being made about antithrombotic treatment for people with atrial fibrillation.

The challenge with tracking health outcomes.

Rising health care costs, questions about the effectiveness of medical interventions and demands for greater accountability and efficiency with respect to health care delivery have led to a growing interest in using patient outcomes as a primary measure of the quality of care. However, measuring outcomes is complex and expensive given the widespread lack of an integrated and comprehensive electronic health information system. Furthermore, the science of outcome measurement is relatively undeveloped and caution needs to be taken when attempting to relate health care provision to differences in outcomes. While the foregoing problems do not invalidate outcome measurement programs, they do stress the point that such initiatives need to be pursued cautiously and that their limitations must be clearly appreciated. The challenge with tracking health outcomes is discussed from the perspective of the Improving Cardiovascular Outcomes in Nova Scotia study. This outcome measurement and management project, one of the most ambitious ever undertaken in Canada, has been seeking to improve the medical care of patients with cardiovascular disease in Nova Scotia since October 1997.