Postmortem study of femoral osteolysis associated with metal-on-metal articulation in total hip replacement: an analysis of nine cases.

BACKGROUND: Improved metal-on-metal articulations were reintroduced in total hip replacement to avoid the osteolysis sometimes seen with conventional ultra-high molecular weight polyethylene bearings. Osteolysis and local lymphocytic infiltration have been reported at revision of some metal-on-metal devices. We report similar and additional results in a study of second-generation metal-on-metal hip implants retrieved post mortem. METHODS: Components and surrounding tissues were collected post mortem from seven patients with nine total hip replacements (Zweymüller SL stem with an Alloclassic cup) with Metasul metal-on-metal articulations. All available patient information was recorded. Radiographs of the hips were evaluated for osteolysis. Sections of joint capsule as well as of the femoral implant with surrounding bone were reviewed, and energy-dispersive x-ray analysis was used to evaluate the composition of wear products. The amount of wear was measured for each component (nine femoral heads and eight cup inserts), when possible, by a coordinate measurement machine with use of the dimensional method. RESULTS: The patients died between three and ten years after arthroplasty, and six of the seven were asymptomatic at the time of death. One patient, with the highest rate of total wear (i.e., wear of femoral head and acetabular cup; 7.6 microm/yr), had increasing hip pain for one year, and histological analysis confirmed the radiographic findings of osteolysis. For two other patients, histological analysis confirmed the radiographic findings of asymptomatic osteolysis. For three patients, histological analysis revealed osteolysis that had escaped conventional radiographic analysis. Joint capsule tissue showed evidence of metallosis in all hips and local lymphocytic infiltration in eight hips. Energy-dispersive x-ray analysis revealed elements attributable to CoCrMo alloy in all hips and traces of corrosion products in three hips. CONCLUSIONS: The postmortem findings of osteolysis and/or lymphocytic infiltration associated with eight clinically well-functioning, low wear devices (a total wear rate of <4 microm/yr) suggest there may be frequent, unappreciated femoral bone loss and local immunological response in patients with second-generation metal-on-metal hip implants. Compared with previous postmortem studies, our findings showed the extent of osteolysis was similar to that with metal-on-polyethylene articulations.

Presence of corrosion products and hypersensitivity-associated reactions in periprosthetic tissue after aseptic loosening of total hip replacements with metal bearing surfaces.

Aseptic loosening of articular implants is frequently associated with tissue reactions to wear particles. Some patients, who had received metal-on-metal articulations, present early symptoms including persistent pain and implant failure. These symptoms raise the suspicion about the development of an immunological response. Furthermore, the generation of rare corrosion products in association with metallic implants has been observed. Corrosion products are known to enhance third-body wear and contribute to the loss of the implant. The purpose of this study was to investigate periprosthetic tissue containing solid corrosion products after aseptic loosening of second-generation metal-on-metal total hip replacements made of low-carbon cobalt-chromium-molybdenum alloy for the presence of immunologically determined tissue changes. Periprosthetic tissue of 11 cases containing uncommon solid deposits was investigated by light microscopy. In order to confirm the presence of corrosion products, additional methods including scanning electron microscopy (SEM) investigation, energy dispersive X-ray (EDX) and Fourier transform infrared microspectroscopy (FTIR) analysis were used. All investigated cases revealed solid chromium orthophosphate corrosion products as well as metallic wear particles to a various extent. Moreover, various intense tissue reactions characteristic of immune response were observed in all cases. The simultaneous presence of corrosion products and hypersensitivity-associated tissue reaction indicates that a relationship between corrosion development and implant-related hypersensitivity may exist.

Catheter-related Leuconostoc bacteremia secondary to pulmonary Mycobacterium xenopi infection.

Infection caused by Leuconostoc spp. is very rare. We report a case of Leuconostoc bacteremia in a patient receiving antimycobacterial chemotherapy for pulmonary Mycobacterium xenopi infection. In addition, the patient presented several known characteristic predisposing factors associated with Leuconostoc infection, such as severe underlying disease, previous long-term antibiotic treatment, indwelling intravascular catheter, prolonged parenteral feeding, previous methicillin-resistant Staphylococcus epidermidis (MRSE) bacteremia with subsequent vancomycin treatment, and prolonged hospitalization. Leuconostoc spp. were isolated from several blood cultures and from a retracted intravascular catheter. After removal of the intravascular catheter the patient's condition improved without additional antibiotic treatment. To our knowledge, this is the first report of a patient with Leuconostoc spp. infection secondary to pulmonary non-tuberculous mycobacteriosis.

Cystic lesion of the groin due to metallosis: a rare long-term complication of metal-on-metal total hip arthroplasty.

We present 2 patients with swelling of the groin after metal-on-metal total hip arthroplasty without radiological signs of component loosening. Magnetic resonance imaging in both patients showed a round intrapelvic lesion ventral to the femoral head. During surgery, we found cystic structures filled with fluid and necrotic masses. After resection of the cyst, the metal head and insert were replaced by a new ceramic head and a polyethylene liner. Although 2 different kinds of alloy were used (Sikomet, low carbon content; Metasul, high carbon content), histopathological analysis in both cases showed typical morphological signs of a hypersensitively determined inflammation. Despite the distinct soft tissue reaction, bony component integration was unaffected. In our opinion, open resection of the cystic lesion and changing of the metal-on-metal articulation is the treatment of choice.

Dedifferentiated chondrosarcoma of the lung: case report and review of the literature.

Primary malignant chondromatoid tumors of the lungs are rare. We report on a case of a 49-year-old woman who presented with a round focus in the upper lobe of the left lung. The performed biopsy showed features of a leiomyosarcoma. After chemotherapy and consecutive tumor resection, the histologic investigation of the entire tumor mass revealed a dedifferentiated chondrosarcoma. Careful clinical and radiologic examinations showed no evidence of further pulmonary and extra-pulmonary tumor lesions. The final diagnosis of a primary dedifferentiated chondrosarcoma of the lung was based on the morphologic criteria and review of the literature. The differential diagnosis of malignant hamartoma was discussed. Follow-up investigation after 2.5 years showed no evidence of another primary tumor site.

Topographical distribution of cerebral amyloid angiopathy and its effect on cognitive decline are influenced by Alzheimer disease pathology.

Cerebral amyloid angiopathy (CAA) is defined by beta-amyloid peptide (Abeta) depositions in cerebral vessels and is associated with Alzheimer disease (AD). It has been suggested that severe CAA is an independent risk factor for cognitive decline. 171 autopsy brains underwent standardized neuropathological assessment, the patients age ranged from 54 to 104 years (mean age: 83.9 years, +/-9.2, 59.6% female, 56.1% clinically demented). Using immunohistochemistry, the severity of Abeta depositions in vessels was assessed semiquantitatively in the frontal, frontobasal, hippocampal, and occipital region, respectively. CAA was present in 117 cases (68.4%), with the occipital region being affected significantly stronger than other regions. The overall incidence of CAA was significantly higher in cases with high grade neuritic AD pathology (ADP) compared to those with low grade or no ADP. The severity of CAA significantly increased with increasing ADP, with CAA in the occipital region increasing significantly stronger than that in other regions. The association of CAA and clinical dementia failed to remain statistically significant when adjusting for concomitant ADP. However, in cases devoid of any ADP CAA was significantly associated with the presence of clinical dementia. These results indicate a strong association of AD with CAA, but do not unequivocally support reports suggesting CAA to be an independent risk factor for cognitive decline, except for a subgroup of demented patients lacking any ADP.

Immunoreactivity of calcium binding protein secretagogin in the human hippocampus is restricted to pyramidal neurons.

Disturbed calcium homeostasis plays a crucial role in the aetiology of Alzheimer's disease (AD) and the aging process. We evaluated immunoreactivity of secretagogin, a recently cloned calcium binding protein, in hippocampus and adjacent entorhinal cortex of 30 neuropathologically examined post mortem brains (m:f=12:18; mean age, 79.8+/-15.1 years). The study group consisted of 15 cases fulfilling the criteria for high probability of AD according to the NIA-Reagan Institute Criteria and 15 cases with no to medium probability. Sections were incubated with secretagogin-specific antibodies and the number of immunoreactive neurons as well as staining intensities in both neurons and neuropil were assessed. Both cellular and neuropil immunoreactivity were restricted to subiculum and Ammons horn. Cellular immunoreactivity was further restricted to pyramidal neurons and showed a hierarchical distribution: the mean percentage of immunoreactive neurons was highest in sector CA3 (64.41%), followed by CA2 (44.09%), CA4 (34.38%), CA1 (10.9%), and the subiculum (2.92%; P<0.001, except CA2-CA4, P>0.05), while it did not differ significantly between groups with different degrees of AD pathology. The pattern of secretagogin immunoreactivity resembles that of calcium sensor proteins as it is restricted to a subset of neurons and therefore secretagogin could serve highly specialized tasks in neuronal calcium signalling.

Cause of death in demented and non-demented elderly inpatients; an autopsy study of 308 cases.

Few studies evaluated cause of death (COD) in elderly demented and non-demented people, the majority based on death certificates alone. The present study is based on autopsy reports with neuropathological examination of 308 inpatients (58.1% female) over age 60 years (mean: 83.5, SD: +/-8.6). CODs were classified into seven groups. The most common were bronchopneumonia (n=117; 38%) and cardiovascular disease (n=116, 37.7%). In 176 patients (57.1%) neuropathology was indicative for dementia: 76.7% Alzheimer disease (AD), 4.5% vascular dementia, 4.0% mixed type dementia (AD + vascular dementia), and 14.8% other dementias. Main COD significantly differed in demented and non-demented patients: bronchopneumonia (45.5% in demented versus 28.0% in non-demented), cardiovascular disease (46.2% in non-demented versus 31.3% in demented). Whereas there were significant differences in COD between AD patients and non-demented ones (bronchopneumonia versus cardiovascular disease), no differences were seen between the latter and patients with other types of dementia than AD. Our data emphasize the high incidence of bronchopneumonia as a COD in patients suffering from AD.

Alzheimer's disease pathology influences severity and topographical distribution of cerebral amyloid angiopathy.

Cerebral amyloid angiopathy (CAA) is defined by beta-amyloid peptide (Abeta) depositions in cerebral vessels and is associated with Alzheimer's disease (AD). The relationship between sporadic CAA and AD, and the origin of Abeta in CAA are poorly understood. The aim of our study was to investigate the relationship between CAA and AD. Autopsy brains (n=113, 61.1% female, 55.8% clinically demented, age range 54-102 years, mean +/- SE 83.5+/-0.93 years) underwent standardized neuropathological assessment. CAA was evaluated in frontal, frontobasal, hippocampal, and occipital regions. Using immunohistochemistry, the severity of Abeta deposition in vessels was assessed semiquantitatively for each region separately. Evaluation of APOE genotype in 53 cases using real-time PCR showed significant correlations with severe AD pathology and CAA. CAA was present in 77 cases (68.1%), with the occipital region being affected significantly more often and more severely than other regions (P<0.01). Of brains without AD pathology 23.5% revealed CAA, whereas 24% with AD pathology showed no CAA. In concordance with other studies, the severity of both AD pathology and CAA showed a low, but significant correlation. This correlation, however, was only caused by the significant increase of occipital CAA with increasing AD pathology (P<0.01), and was independent of APOE genotype. Our results suggest that progressing AD pathology not only increases the severity of CAA, but also shifts its topographical distribution towards the occipital cortex.

Olfactory involvement in aging and Alzheimer's disease: an autopsy study.

Olfactory dysfunction and tau pathology in the olfactory bulb increase with the severity of Alzheimer's disease. We report data of a postmortem study in the aged. 130 autopsy cases (81 female, 49 male, aged 61-102, mean 82.48 +/- 4.35 SD) years, underwent a standardized neuropathological assessment with immunohistochemical study of tau pathology in the olfactory bulb and nerve and of Alzheimer's disease using established criteria including Braak staging. All cases of definite Alzheimer's disease (Braak stages 5 and 6) (n = 40) showed large numbers of neuropil threads and neurofibrillary tangles, with amyloid deposits in 32.5% and neuritic plaques in one single case in the olfactory system. Braak stage 4 (n = 27) was associated with mild to moderate tau pathology in 85.2%, and amyloid plaques in 1.1%, Braak stage 3 (n = 28) with olfactory tau lesions in 37.0% and amyloid deposits in one single case, Braak stages 3 and 4 with olfactory tau lesions in 61.1%. Braak stage 2 (n = 15) showed olfactory tau pathology in 31.2%, whereas Braak stages 0 and 1 (n = 15) were all negative. The olfactory system tau score showed highly significant correlations with neuritic Braak stages in the brain, while both scores showed significant but low correlations with age. These data confirm previous studies demonstrating abundant tau pathology in the olfactory system in all definite Alzheimer's disease cases, in two-thirds of limbic Alzheimer's disease, and in almost one-third of non-demented elderly persons with Braak stage 2. There are strong correlations between tau pathology in the olfactory and limbic systems, both with similar increase in severity. Clinical dementia correlated with both Braak and olfactory system tau scores. Since the involvement of both systems is associated with a high risk of cognitive decline, future studies should validate the sensitivity of olfactory mucosa biopsies in the diagnosis of Alzheimer's disease.

The clinical diagnostic accuracy rate regarding the immediate cause of death in a hospitalized geriatric population; an autopsy study of 1594 patients.

BACKGROUND: In the geriatric population the autopsy rate is low, leading to mortality statistics often based on clinical diagnoses alone. OBJECTIVES: To determine the clinical diagnostic accuracy rate regarding the immediate cause of death (CDARCD), the number of major underlying diseases and sole diagnoses, and general data about the immediate cause of death in geriatric hospitalized patients. METHODS: The autopsy proven immediate cause of death was compared with the clinical diagnosis in 1594 patients over 69 years of age. Based on the autopsy protocols, the mean number of major underlying diseases and sole diagnoses were calculated. The immediate cause of death was classified into six groups: cardiovascular disease (CVD), malignant neoplasms (MN), bronchopulmonary disease (BPD), fatal pulmonary embolism (PE), miscellaneous (M), and marantic atrophy (MA). RESULTS: The overall CDARCD was 52.5%, being highest in MN (65.0%), followed by CVD (56.0%), MA (50%), BPD (48.3%), M (44.3%), and PE (26.7%). The most common cause of death was CVD (35.8%), followed by MN (24.3%), BPD (19.8%), PE (10.6%), M (7.7%) and MA (1.9%). The mean number of major underlying diseases and sole diagnoses was 2.0 and 14.4 respectively. CONCLUSIONS: The low CDARCD in our study strongly indicates the need for autopsy when reliable mortality statistics are desired.

Amyloid beta peptide 1-42 highly correlates with capillary cerebral amyloid angiopathy and Alzheimer disease pathology.

Recent studies reported both positive [Thal et al. (2003) J Neuropathol Exp Neurol 62:1287-1301] and negative [Tian et al. (2003) Neurosci Lett 352:137-140] correlations between cerebral amyloid angiopathy (CAA) and Alzheimer's disease (AD) pathology. We have recently shown high correlations between neuritic AD pathology and amyloid beta peptide (Abeta) deposits in the capillary/pericapillary compartment (CapCAA) with only low correlations to general CAA (non-capillary). We have now studied the relationship between CapCAA and AD pathology with respect to the distribution of Abeta40 and 42 in the frontal cortex of 100 human postmortem brains from both male and female, demented and non-demented patients (mean age +/- SD 84.3 +/- 9.3 years). Using polyclonal antibodies to Abeta40 and 42, capillary and plaques positivity were assessed semiquantiatively on a four-point scale. Abeta42 deposits in capillaries correlated highly with both Abeta42 deposits in plaques and morphological AD criteria (CERAD, Braak stages, and NIA-Reagan-Institute criteria), while only a low correlation with CAA was observed. Abeta40 deposits in capillaries differed morphologically from Abeta42 ones: they were limited to capillary walls, were significantly less frequent in both capillaries and plaques compared to Abeta42 ( P < 0.01), and showed a low correlation with morphological AD criteria ( P < 0.05) and general CAA ( P < 0.01). By contrast, Abeta42 deposits were seen in the glia limitans rather than in capillary walls themselves, and showed high correlation with morphological AD criteria ( P < 0.01). These data indicate that CapCAA is characterized by Abeta42 deposits in pericapillary spaces or in the glia limitans. A low correlation between CAA and CapCAA, but high correlations between morphological AD criteria and CapCAA suggest different pathomechanisms for both types of CAA, and a close relation between CapCAA and AD pathology (both neuritic and plaque type). These data support the concept of a neuronal origin of Abeta via drainage from interstitial fluid from the central nervous system along basement membranes to capillaries.

Retrieval study of uncemented metal-metal hip prostheses revised for early loosening.

A tribologic assessment was performed on 22 metal-metal hip prostheses from a single manufacturer, following removal for early aseptic loosening after a mean service life of 32 months (range, 12-59 months). The mean linear wear rate was 7.6 microm/year (range, 2.9-12.8 microm/year). This was below the rates previously observed in other modern metal-metal combinations. A novel contour analysis technique using a coordinate measuring machine showed the mean volumetric wear rate to be 2.02 mm(3)/year (range, 0.55-3.74 mm(3)/year), which corresponds to a mean gravimetric wear rate of 16.9 mg/year (range, 4.6-31.4 mg/year). The mean clearance of 39.8 microm (range, 30-50 microm) was within the optimal range for hard-hard bearing combinations. Evidence of abrasive, adhesive, and third-body wear was found on all bearing surfaces. The tribologic assessment did not indicate manufacturing defects as a cause of early loosening. Equally, third-body wear was too low to be considered a causative factor for early loosening.

Detection of the Epstein-Barr virus in primary adenocarcinoma of the lung with Signet-ring cells.

The Epstein-Barr virus (EBV) is directly implicated in the pathogenesis of a variety of undifferentiated carcinomas and has also been identified in conventional adenocarcinomas of the stomach. To date, the association of EBV with non-small cell lung carcinoma is restricted to Asian patients. To evaluate the presence of EBV in lung cancers from Europeans, we investigated primary lung adenocarcinomas with a similar morphological tumour pattern to those of the stomach, specifically rare tumours with components of signet-ring cells. Three tumours of signet-ring cell type were examined by means of polymerase chain reaction (PCR). To localise the virus to the neoplastic cells, in situ hybridisation (ISH) was performed using an antisense Epstein-Barr virus encoded RNA probe. Immunohistochemistry was performed to evaluate the expression of latent membrane protein-1 (LMP-1) and EBV nuclear antigen 2 (EBNA-2). PCR investigation confirmed the presence of EBV in one case. Positive signals confined to tumour cells were present on ISH. None of the tumours showed expression of LMP-1 and EBNA-2. To our knowledge, this is the first report on the presence of EBV in primary adenocarcinoma of the lung in a Caucasian patient. The present study indicates that EBV may infect some lung cancers with a specific tumour pattern.

Successful hip arthroplasty using cementless titanium implants in rheumatoid arthritis.

Over a period of eight years, we implanted a total of 76 cementless hip prostheses in patients with rheumatoid arthritis. The clinical results of 47 patients (70 hips) increased from a mean Harris Hip Score of 33 to 85 after an average of 49 months (range 1-11 years). One threaded cup has had to be revised because of loosening, and one stem because of femoral fracture. At the latest follow-up, 88% of Hofer-Imhof threaded cups had complete bone ingrowth (Type 0); 10% had near-complete bone ingrowth with minimal radiolucency in one third of the bone contact area (Type 1), and 2% had radiolucency in two thirds of the bone contact area (Type 2). Hemispherical push-in cups showed significantly more radiolucency around the cup. For the stems (Uni, Zweymüller SL), 83% showed no radiolucency (Type 0); 17% had radiolucency only very proximally (Type 1). Minor remodelling (Type 1) occurred in 60% of the femoral shafts; 30% had moderate femoral density loss (Type 2), and 10% had severe bone loss and cortical thinning (Type 3). There was no correlation between marked shaft atrophy and clinical symptoms. With regard to radiolucency and remodelling, there was no significant difference between the two types of stem used. Cementless hip arthroplasty using titanium implants has an excellent outcome in the medium term.