Felix Lintner

Anatomy, biochemistry, and physiology of articular cartilage.

Huber M, Trattnig S, Lintner F. Anatomy, biochemistry, and physiology of articular cartilage. Invest Radiol 2000;35:573–580. ABSTRACT.Articular cartilage serves as a load-bearing elastic material that is responsible for the frictionless movement of the surfaces of articulating joints. Its ability to undergo reversible deformation depends on its structural organization, including the specific arrangement of the matrix macromolecules and the chondrocytes. Interactions between the matrix and chondrocytes are responsible for the biological and mechanical properties of articular cartilage and enable it to respond by effecting a balance between anabolism and catabolism as well as continual internal remodeling. Age-related changes in the function of chondrocytes may contribute to the initiation and progression of osteoarthritis.

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.

Neuropathology and general autopsy findings in AIDS during the last 15 years

Abstract A retrospective study of 450 consecutive AIDS autopsy cases (397 males, 53 females; mean age at death 38.4 years) in Vienna, Austria, between 1984 and 1999 compares the central nervous system (CNS) findings in three cohorts: 1984–1992 (190 cases), 1993–1995 (162 cases) and 1996–1999 (98 cases, after introduction of triple antiretroviral therapy) and the relationship of CNS findings to systemic AIDS pathology in the latter two cohorts. In these two groups, following involvement of the lung (85% and 75%, respectively), the brain continued to be the second most frequently involved organ (decrease from 80% to 60%, respectively). Extracerebral protozoal (Pneumocystis carinii, toxoplasmosis), Mycobacterium avium complex, viral [e.g., cytomegalovirus (CMV)], multiple opportunistic organ and CNS infections, and Kaposi sarcoma significantly decreased over time. There was less decrease in fungal infections, while bacterial organ and CNS infections (except for mycobacteriosis), lymphomas, HIV-associated CNS lesions (around 30%), non HIV-associated changes (vascular, metabolic, etc.) and negative CNS findings (10–11%) remained unchanged. Nonspecific CNS changes (e.g., meningeal fibrosis) increased. Extracerebral pathology in subjects with advanced HIV-related CNS lesions showed more frequent but decreasing systemic bacterial and CMV infections than those with negative or nonspecific neuropathology, while other opportunistic and multiple organ infections and lymphomas showed no differences between both groups. In a cohort of drug abusers, HIV encephalitis, progressive multifocal leukoencephalopathy, bacterial infections, hepatic encephalopathy, and negative CNS findings were more frequent than in non-users who showed increased incidence of CMV, toxoplasmosis, or other opportunistic CNS infections, and nonspecific CNS findings; the frequency of lymphomas was similar in both drug abusers and non-users. Similar to a recent autopsy study from San Diego, these data suggest that despite the beneficial effects of modern antiretroviral combination therapy, involvement of the brain in AIDS subjects continues to be a frequent autopsy finding, while the increased incidence of HIV encephalitis in our small cohort of drug users was less than observed in other recent autopsy studies.

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 Alzheimers 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 Alzheimers disease using established criteria including Braak staging. All cases of definite Alzheimers 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 Alzheimers disease cases, in two-thirds of limbic Alzheimers 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 Alzheimers disease.

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.

Tissue reactions to titanium endoprostheses. Autopsy studies in four cases.

Four cementless prosthetic hip implants of Ti-6Al-4V-alloy with and without longitudinal grooves and Al2O2 ceramic ball heads, with implant periods of 3, 4, 5, and 10 months, were sectioned and examined histologically in undecalcified thin ground sections. Especially on the medial and lateral sides of the prostheses, there was direct bone-to-metal contact without interposed connective tissue, spreading to the dorsal and ventral areas of the prosthesis shaft, which was considered osseointegration. This is based mainly on the technique of implantation with primary stability in the cortical bone by press-fit and on the bioinertness of the titanium alloy. Ungrooved prosthesis areas seem to favor bone growth at the shaft. The secondary bone ring, occurring on the dorsal and ventral areas of the prosthesis, with evidence of further bone remodeling with the passage of time, indicates that osseointegration is a dynamic process that continues to improve prosthetic stability.

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.

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.

Cytomegalovirus infection of the brain in AIDS: a clinicopathological study

Based on neuropathological findings, a retrospective case control study of 39 patients with acquired immune deficiency syndrome (AIDS) and confirmed cytomegalovirus (CMV) infection of the brain is presented. Since 1989, the incidence of cerebral infections in AIDS autopsy material has increased progressively and, in 1994, CMV was the most frequent opportunistic central nervous system (CNS) infection. Of the patients with CMV infections of the brain 16 had one or more coexisting secondary opportunistic and/or tumorous lesions in the CNS. Cerebral involvement by CMV was more frequent in patients with multiple extracerebral organ infections, while 7 among the 39 reported cases showed isolated CMV infection of the brain. The evaluation of the clinical records of 21 patients revealed neuropsychiatric signs and symptoms in 10, while these were absent in 11. All of these patients revealed various types of cerebral lesions related to CMV infection: ventriculitis, focal lesions, and microglial nodule encephalitis. The extent and distribution of cerebral lesions showed no significant correlations with clinical, radiological, or laboratory findings. Further clinicopathological studies are warranted to recognize CMV infections of the CNS and to allow earlier and more efficient treatment of this rather frequent complication of AIDS.

Calcium‐binding protein secretagogin‐expressing neurones in the human hippocampus are largely resistant to neurodegeneration in Alzheimer's disease

The pathological findings in Alzheimers disease (AD) are partly attributed to alterations in calcium‐binding protein (CBP) functions. We showed previously that immunoreactivity of secretagogin, a recently cloned CBP, in the human hippocampus is restricted to pyramidal neurones and that the amount of immunoreactive neurones does not differ between AD cases and controls. In this study we investigate the influence of hippocampal tau pathology on secretagogin expression in more details. The study group consisted of 26 cases with different degrees of neuropathologically confirmed AD pathology. Sections were incubated separately with secretagogin‐ and tau‐specific antibodies, respectively. The amount of immunoreactive neurones and integral optical densities were assessed. In addition, double immunofluorescence for both secretagogin and tau was performed. No difference with respect to secretagogin immunoreactivity was observed in different stages of AD pathology, and similarly no significant associations were seen between the amount of secretagogin and tau immunoreactivity in the different hippocampal subfields. Double immunofluorescence revealed that both proteins rarely colocalize because only 5.3% of tau and 2.9% of secretagogin immunoreactive neurones, respectively, showed colocalization. Because there are no differences in the amount of hippocampal secretagogin expression between AD cases and controls (as we have shown previously), the lack of an association between the amount of secretagogin expression and tau burden together with the low frequency of colocalization of tau and secretagogin in the human hippocampus, suggest that secretagogin‐expressing neurones are largely resistant to neurodegeneration in AD.