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

The pathological findings in Alzheimer's 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.

Lung disease 35 years after aspiration of activated charcoal in combination with pulmonary lymphangioleiomyomatosis. A histological and clinicopathological study with scanning electron microscopic evaluation and element analysis.

Activated charcoal provides effective treatment for most toxic ingestions. Accidental aspiration of activated charcoal is rare. Previously, there have been a few single cases reported on charcoal-related pulmonary complications. We describe an unusual case of pulmonary lesions 35 years after accidental aspiration of activated charcoal. The 38-year-old female patient presented with recurrent pneumothorax. A routinely performed chest roentgenogram revealed pulmonary lesions, highly suggestive to lymphangioleiomyomatosis (LAM). Histopathological investigation of the lung tissue demonstrated some features of LAM but showed prominent pneumoconiotic lesions with cystic tissue destruction. The pneumoconiotic reaction was characterized by prominent black deposits accompanied by foreign-body granuloma formation and minimal fibrosis. Scanning electron microscopic investigation of these deposits showed particles measuring up to 300 microm in greatest diameter. Energy-dispersive X-ray spectra of these particles revealed carbon-rich material, presumably charcoal. The aspiration event was confirmed by the clinical history. To our knowledge, this is the first report not only on a long-term follow-up after aspiration of activated charcoal but also on charcoal-related pulmonary lesions in combination with LAM.

Proposal for a histopathological consensus classification of the periprosthetic interface membrane.

AIMS: The introduction of clearly defined histopathological criteria for a standardised evaluation of the periprosthetic membrane, which can appear in cases of total joint arthroplasty revision surgery. METHODS: Based on histomorphological criteria, four types of periprosthetic membrane were defined: wear particle induced type (detection of foreign body particles; macrophages and multinucleated giant cells occupy at least 20% of the area; type I); infectious type (granulation tissue with neutrophilic granulocytes, plasma cells and few, if any, wear particles; type II); combined type (aspects of type I and type II occur simultaneously; type III); and indeterminate type (neither criteria for type I nor type II are fulfilled; type IV). The periprosthetic membranes of 370 patients (217 women, 153 men; mean age 67.6 years, mean period until revision surgery 7.4 years) were analysed according to the defined criteria. RESULTS: Frequency of histopathological membrane types was: type I 54.3%, type II 19.7%, type III 5.4%, type IV 15.4%, and not assessable 5.1%. The mean period between primary arthroplasty and revision surgery was 10.1 years for type I, 3.2 years for type II, 4.5 years for type III and 5.4 years for type IV. The correlation between histopathological and microbiological diagnosis was high (89.7%), and the inter-observer reproducibility sufficient (85%). CONCLUSION: The classification proposed enables standardised typing of periprosthetic membranes and may serve as a tool for further research on the pathogenesis of the loosening of total joint replacement. The study highlights the importance of non-infectious, non-particle induced loosening of prosthetic devices in orthopaedic surgery (membrane type IV), which was observed in 15.4% of patients.

Anatomically adapted, HA coated SBG stem--ten years of successful implantation.

For stable implantation of anatomically conforming femur prostheses, modifications that accommodate curving and torsion are necessary. In accordance to this concept, the anatomically shaped SBG stem has been developed. The first consecutive implantations were evaluated. 194 primary arthroplasties with uncemented anatomical, HA coated SBG stems were performed. Mean patient age was 61 years. 143 patients with 151 (78%) SBG stems were followed-up clinically and radiologically after an average of 10 (9-11) years. So far, only one implant had to be revised. Survivorship with revision of the femoral component is 99.5% at ten years. The mean postoperative Harris Hip Score was 92. Patients over 75 years had a score of 89; younger patients under 40 years scored 94. Sclerotic lines were seen in zone I or VII in 8%. Minor femoral remodeling (Type 1) occurred proximally in 75%. Minor thickening of the femur at the level of the tip of the prosthesis could be observed in 27% of the cases. There is no correlation between compacta thickening and clinical symptoms (p=0.15). The anatomical shape, the oval diameter and the longitudinal grooves secure stable primary fixation. Together with the HA coating, which enhances osseointegration, the SBG stem has a high success rate in the medium and long term.

[The modular hip revision stem made of titanium alloy--influence and optimisation of bending stiffness]. / Modulare Hüftrevisionsschäfte auf Titanbasis--Einfluss und Optimierung des Steifigkeitsverhaltens.

UNLABELLED: The MRP-Titan Revision stem has proved to be a highly successful implant system for revision arthroplasty of the hip. Good and excellent clinical and radiological results with spontaneous filling of bony defects have been reported, The observation of atrophy of the proximal femur associated with stem diameters > 17mm prompted us to examine the bending stiffness of stems of various diameters. To determine their static bending characteristics, the stems were tested under axial pressure loads in accordance with Euler's buckling case. Dynamic tests were performed with the mono-axial servohydraulic test equipment MTS 810. From a stem diameter of 18 mm upwards, deflection of the stem under loading decreased disproportionately, in direct correlation with the stem stiffness. By optimising the geometry and varying the alloy it is possible to obtain a constant ISD factor for the modular MRP-Titan revision stem CONCLUSION: The MRP-Titan revision stem is a reliable implant system for revision arthroplasty of the hip. Clinical findings of atrophy of the proximal femur associated with stem diameters > 17 mm was found to be correlated with a disproportionate increase in bending stiffness. The aim of further developments will be to reduce the stiffness of larger-diameter stems by making changes to the design and/or to the alloy (Ti15Mo, Ti13Nb13Zr, Ti12Mo6Zr2Fe2).

[Proposal for the classification of the periprosthetic membrane from loosened hip and knee endoprostheses]. / Vorschlag für eine Konsensus-Klassifikation der periprothetischen Membran gelockerter Hüft- und Knieendoprothesen.

After 10 years, loosening of total joint endoprostheses occurs in about 3 to 10 percent of all patients, requiring elaborate revision surgery. A periprosthetic membrane is routinely found between bone and loosened prosthesis. Further histomorphological examination allows determination of the etiology of the loosening process. Aim of this study is the introduction of clearly defined histopathological criteria for a standardized evaluation of the periprosthetic membrane. Based on histomorphological criteria and polarized light microscopy, four types of the periprosthetic membrane were defined: periprosthetic membrane of wear particle type (type I), periprosthetic membrane of infectious type (type II), periprosthetic membrane of combined type (type III), periprosthetic membrane of indifferent type (type IV). Periprosthetic membranes of 268 patients were analyzed according to the defined criteria. The correlation between histopathological and microbiological diagnosis was high (89%, p<0,001), the inter-observer reproducibility was sufficient (95%). This classification system enables a standardized diagnostic procedure and therefore is a basis for further studies concerning the etiology of and pathogenesis of prosthesis loosening.

Stress analysis of threaded cups.

Using finite element analysis we have studied the pelvic bony socket and compared it with radiological imaging using threaded acetabular cups of three different shapes (parabolic, conical, hemispherical). The two-dimensional model depicted a planar section through a left pelvic hemisphere. In all three cups the stress in the bony socket increased from lateral towards medial. Compressive stress was found on the superior and inferior parts of the cup, but mainly on the superior aspect, seen radiologically as new trabecular bone formation. The maximum compressive stresses were seen in the cranial curvature of the conical cup, with less in the parabolic form and least in the hemispheric form. The tensile stress at the bottom of the socket increased from the hemispheric to the conical shape. Radiological rarefaction gave an indication of lower stress. There was lower compressive stress between the teeth of the threads. This FE model uses computer simulation to predict bony changes with different designs of implant. The ability to simulate biological conditions is a valuable addition to the testing of mechanical strength.

Pseudomesotheliomatous adenocarcinoma of the lung with rhabdoid features.

Pseudomesotheliomatous adenocarcinoma of the lung is a rare entity, clinically and pathologically mimicking diffuse malignant pleural mesothelioma. We report a case of pseudomesotheliomatous adenocarcinoma consisting of two distinct histopathologic components with marked differences in morphological appearance and immunohistochemical staining pattern: a small subpleural nodule consisting of adenocarcinoma and undifferentiated carcinoma with rhabdoid features, the latter extending to the visceral pleura in a diffuse mesothelioma-like growth pattern. The adenocarcinomatous component showed strong reactivity with various epithelial markers, but no reactivity with vimentin. The undifferentiated component showed strong reactivity for vimentin, but no reactivity for epithelial markers. Both components showed no reactivity with CEA, Ber Ep4, MOC-31, B72.3, cytokeratin 5/6, calretinin and thrombomodulin. Metastatic lesions in the duodenum and the periumbilical skin consisted entirely of undifferentiated carcinoma with rhabdoid features. Fluorescence in situ hybridisation (FISH) was performed for chromosomes 4, 7, 20, and 22. FISH results showed polysomy 7 in both components. The diagnosis of pseudomesotheliomatous adenocarcinoma in this case was based on the finding of the subpleural nodule. We conclude that in cases of undifferentiated malignant pleural tumors with cells of rhabdoid phenotype, the possibility of peripheral pulmonary adenocarcinoma dedifferentiating into a more aggressive phenotype should be considered.

Morphometric examination of straight, tapered titanium stems: a retrieval study.

Cementless straight, tapered rectangular cross section titanium stems have been used by the senior author since 1979. Thirty-four stems retrieved postmortem, after between 10 days and 15.2 years in situ, were studied morphometrically and histologically. Nineteen stems were first generation (1979-1986), with an incomplete sagittal taper and a mean surface roughness of 1 microm (Ra 1.23 +/- 0.3 microm); 15 stems were second generation after 1986, with a full biplane taper and a mean surface roughness of 4 microm (Ra 4.14 +/- 0.36 microm). Implant surface bony coverage was determined morphometrically in 10 segments of the stems, and expressed as a bone implant contact index. Histologically, there were no differences between implants with different levels of roughness. Morphometrically, the first-generation stems showed significant differences in coverage (distal > proximal); second-generation stems had a more uniform pattern. Stems retrieved early after arthroplasty had a mean bone implant contact index of 10%. The mean bone implant contact index showed attainment of maximum coverage by 5 years after arthroplasty, without additional apposition or loss thereafter. Patients younger than 65 years at arthroplasty had similar bone implant contact indices to patients 65 years or older; coverage in the six patients 80 years of age at retrieval did not differ from the rates in the other patients. Morphometry was able to provide objective evidence of design change effects. No differences in coverage were found in terms of times in situ, patient age at arthroplasty and at retrieval, and degree of stem surface roughness.

Anatomy, biochemistry, and physiology of articular cartilage.

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.

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

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.

Experimental study of bone-implant contact with a parabolic acetabular component (Hofer-Imhof).

Incomplete bone contact with threaded acetabular components is usually attributable to the tapered thread design and sclerotic bone, and might be the reason for early loosening. The self-tapping flat threads of the Hofer-Imhof cup allow accurate insertion without incarceration, even in sclerotic bone. To demonstrate the effectiveness of this threaded cup design based on digitized measurements of bone contact area, six Hofer-Imhof cups were implanted into three human cadavers. The bone contact area at the threads was digitally analyzed on cadaver-explanted cups cut into horizontal and coronal sections. In cups fixed with ideal form fit, bone contact was 31.6% (range 8-55%) at the threads and 28.5% (range 0-49%) between the threads on average. In cups with incomplete bone contact secondary to insufficient reaming, the bone contact area averaged 27.4% (range 10-44%) at the threads. In sclerotic bone, the highest bone contact at the threads was 69%. The threads were the first part of the cup to achieve primary bone contact. Factors contributing to poor contact were incomplete reaming, sections which passed through the incisura of the acetabulum, and incomplete contact with the medial aspect of the acetabulum. The aim was to achieve complete bone contact. Because of the higher contact areas observed in sclerotic bone, some sclerotic bone should remain after reaming.

Multiple endometrial stromal nodules with sparse cysts and glands in the lung--a nodular variation of endometriosis that may mimic metastases of sarcoma.

We report an unusual case of a nodular variation of pulmonary endometriosis. To our knowledge, there is no previous report on a morphological investigation of this entity. The etiology of this rare condition is still a matter of discussion. The well-circumscribed nodular mass is composed of cells identical to, or closely resembling, those of endometrial stroma containing sparse cysts and glands. Immunohistochemically, the cells showed an extensive co-expression of cytokeratin AE1/AE3 and vimentin and were highly positive for progesterone receptor (PRICA) and estrogen receptor (ERICA). Cells lining the cysts and glands as a monolayer were reactive for Ber-Ep4, cytokeratin Pan and cytokeratin AE1/AE3 and negative to all other markers used including PRICA and ERICA. The differential diagnosis of this entity included fibrous tumor of the pleura and metastatic low-grade-endometrial-stromal-sarcoma. The morphological findings are correlated with immunohistochemical studies and results of cell image analysis. This study details the clinicopathological features of the nodular variation of pulmonary endometriosis.

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 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.

Histology of tissue adjacent to an HAC-coated femoral prosthesis. A case report.

We studied the fixation of a cementless titanium femoral prosthesis partially coated with hydroxyapatite ceramic (HAC) 10.4 months after implantation. Histomorphological investigation showed extensive new bone formation between the HAC coating and the bone bed; morphometry showed bone contact indices of up to 91.60%. There were a number of resorption lacunae on the HAC coat with depths of up to 76.6 microns and widths of up to 453 microns. Our results confirmed that considerable bone remodelling had taken place and that the apatite-coated prosthesis had united with bone despite the lack of appreciable immediate press-fit. Hydroxyapatite particles which had been released did not appear to show any negative effects on the stability of the implant.

Spindle cell variant of pulmonary adenocarcinoma.

A 45-year-old male developed a transverse lesion of the spinal cord two years after resection of a pulmonary adenocarcinoma. Laminectomy revealed a spindle cell tumor, immunohistochemically considered as leiomyosarcoma. Autopsy disclosed a spindle cell variant of an adenocarcinoma of the lung. The present report demonstrates that spindle cell formations can be found not only in squamous cell carcinomas but also in adenocarcinomas of the lung, and that metastases may be composed of this spindle cell component only.

Postpartum hemolytic uremic syndrome following placental abruption.

Hemolytic uremic syndrome associated with pregnancy is a rare condition. Authors report a patient treated with corticosteroids for bronchial asthma who was afflicted by placental abruption at 24 weeks' gestation. The abruption was preceded by developing herpes zoster and by deteriorating respiratory symptoms. The induced labor was followed by anuria, acute renal failure, microangiopathic hemolytic anemia, thrombocytopenia then fever and hypertension. The patient was treated early with plasma infusion, transfusion and hemodialysis. She recovered completely after 7 weeks. This case seems to be unique inasmuch as the hemolytic uremic syndrome was preceded by prodromal illness during pregnancy and was associated with placental abruption.

Magnesium content of human myometrium and placenta during various stages of gestation, and of different body fluids at term.

Pregnancy is marked by a state of hypomagnesaemia but not much is known about the effects of maternal magnesium deprivation on the fetus. The aim of this study was therefore to measure magnesium concentrations in human myometrial and placental tissues and in different body fluids during pregnancy and at term, using atomic absorption spectrophotometry. The magnesium concentration in umbilical cord blood was higher than in the maternal blood, supporting the existence of an active magnesium transport system. There was also a difference between the magnesium concentration in the amniotic fluid and that in the umbilical cord blood. The magnesium content of myometrium increased from the 32nd week of pregnancy, reaching its maximum level at the 37th week of gestation. Later there was significant decrease in magnesium level until the end of pregnancy. The magnesium content of placental tissue did not change up to the 30th week of pregnancy; however, it then decreased continuously during the last trimester. The significant improvement experienced in certain pathological conditions of pregnancy treatment with magnesium supports the existence of a magnesium deficit induced by pregnancy and the need for magnesium supplementation.

[Pathology of the central nervous system in AIDS. An overview of 184 patients]. / Pathologie des Zentralnervensystems bei AIDS. Ein Uberblick über 184 Patienten.

Based on a consecutive autopsy series of 184 patients with AIDS, a critical review of the pathology of the central nervous system (CNS) is given. The lesions can be divided into three groups: 1. opportunistic/non-opportunistic infections, 2. changes due to the human immunodeficiency virus (HIV), and 3. neoplasms. The frequency and morphology of CNS lesions in our cohort are compared with those in other series. Marked lesions of the CNS were found in 111 patients (60%), while mild/nonspecific changes were seen in 52 cases (28%). Toxoplasmosis (23%) was the most frequent CNS infection, followed by cytomegalovirus (17%), and papovirus (5%). HIV giant cell encephalitis, HIV leukoencephalopathy, vacuolar myelopathy and leukoencephalopathy were observed in 11%. Primary CNS lymphomas were present in 6%, while secondary involvement of the CNS in systemic lymphomas was seen in only two cases (1%). Lesions due to CNS infections in patients with AIDS often show atypical patterns, and frequently, there are multiple infections with simultaneous involvement of the CNS by lesions of different etiology. The present study confirms the frequent involvement of the CNS in AIDS, although there are differences in the incidence and pattern of lesions related to geographic and/or demographic factors.

[Comparative morphological studies on the incorporation of various cementless implanted artificial patellas]. / Vergleichende morphologische Untersuchungen zum Einbauverhalten verschiedener zementfrei implantierter künstlicher Kniescheiben.

Twelve uncemented, artificial patellar components clinically and radiologically without signs of loosening after an implantation period of 9-48 Months were investigated histologically and microradiographically. The components correspond to the system GSB-"old", GSB-"new", PCA and APS. Within the observed implantation period the artificial patellar components GSB-"old", GSB-"new" and PCA showed severe patho-morphological changes of the surrounding tissue and point to loosening. The dowel system according to APS shows after the longest period of time of 14 Months morphologically a fully bony encasement with wide spread direct contacts between the living bone and the metallic Titanium surface. The observation points urgently to the fact, that Polyethylene must not be in direct contact with the bony bed. On the basis of the patho-morphological reactions a partial armament of the polyethylene surface with metallic structures must be rejected as a general principle.