[Chondrocalcinosis. Clinical impact of intra-articular calcium phosphate crystals]. / Chondrokalzinose. Klinische Bedeutung von intraartikulären Kalziumphosphatkristallen.

Calcium pyrophosphate dihydrate (CPPD) crystals are known to cause acute attacks of pseudogout in joints but crystal deposition has also been reported to be associated with osteoarthritis (OA). Aside from CPPD crystals, basic calcium phosphates (BCPs), consisting of carbonate-substituted hydroxyapatite (HA), tricalcium phosphate and octacalcium phosphate, have been found in synovial fluid, synovium and cartilage of patients with OA. Although CPPD crystals have been found to be associated with OA and are an important factor in joint disease, this has also recently been associated with a genetic defect. However, according to the most recent findings, the association of BCP crystals, such as apatite with OA is much stronger, as their presence significantly correlates with the severity of cartilage degeneration. Identification of BCP crystals in OA joints remains problematic due to a lack of simple and reliable methods of detection. The clinical and pathological relevance of cartilage mineralization in patients with OA is not completely understood. It is well established that mineralization of articular cartilage is often found close to hypertrophic chondrocytes. A significant correlation between the expression of type X collagen, a marker for chondrocyte hypertrophy and cartilage mineralization was observed. In the process of endochondral ossification, the link between hypertrophy and matrix mineralization is particularly well described. Hypertrophic chondrocytes in OA cartilage and at the growth line share certain features, not only hypertrophy but also a capability to mineralize the matrix. Recent data indicate that chondrocyte hypertrophy is a key factor in articular cartilage mineralization strongly linked to OA and does not characterize a specific subset of OA patients, which has important consequences for therapeutic strategies for OA.

Decreased levels of nucleotide pyrophosphatase phosphodiesterase 1 are associated with cartilage calcification in osteoarthritis and trigger osteoarthritic changes in mice.

OBJECTIVE: To analyse the function of nucleotide pyrophosphatase phosphodiesterase (NPP1), a member of the pyrophosphate pathway, in osteoarthritis (OA). METHODS: mRNA expression of NPP1, ANK ankylosing protein and tissue non-specific alkaline phosphatase was assessed by quantitative PCR. NPP1 protein levels were analysed in mouse and human cartilage samples. Bone metabolism was analysed by F18-positron emission tomography-scanning and µCT in ttw/ttw mice. Ttw/ttw mice are mice carrying a loss-of-function mutation in NPP1. Calcification of articular cartilage was assessed using von Kossa staining and OA severity using the Mankin score. Cartilage remodelling was investigated by type X collagen immunohistochemistry. RESULTS: Expression of NPP1, but not the other members of this pathway, inversely correlated with cartilage calcification and OA severity in mouse and humans. Proinflammatory cytokines downregulated the expression of NPP1, demonstrating an influence of inflammation on matrix calcification. Ttw/ttw mutant mice, carrying a loss-of-function mutation in NPP1, exhibit increased bone formation process in joints compared with wild types. Ttw/ttw mice also developed spontaneous OA-like changes, evaluated by histological analysis and in vivo imaging. Ectopic calcifications were associated with increased expression of collagen X in the cartilage. CONCLUSION: The authors conclude that OA is characterised by the reactivation of molecular signalling cascades involving proinflammatory cytokines, thereby regulating the pyrophosphate pathway which consequently leads to cartilage ossification, at least in part resembling endochondral ossification.

[Approach to painful hip resurfacing]. / Vorgehen bei schmerzhafter Kappenprothese.

Hip resurfacing in young patients has been increasingly performed within the last decade. In comparison to standard total hip arthroplasty the failure rate remains high. Age and implant size have a significant effect on the risk of revision for primary total resurfacing and the risk of revision increases with increasing age. At 7 years the cumulative revision rate for patients is 5% and females have more than twice the cumulative revision rate as males. Even in hip resurfacing arthroplasty which has been performed in a perfect manner, a certain percentage of patients suffer from persistent pain for various reasons, such as neck fracture, iliopsoas tendinopathy, metal hypersensitivity, such as aseptic lymphocytic vasculitis associated lesions (ALVAL) and aseptic loosening. Diagnostic work-up of the painful hip resurfacing is challenging even for experienced surgeons. Recommendations for the diagnostic procedure are described.

[Crystal arthropathies]. / Kristallarthropathien.

Crystal arthropathies represent a heterogenic group of skeletal diseases associated with the deposition of mineralised material within joints and periarticular soft tissues. Gout is the most common and pathogenetically best understood crystal arthropathy, followed by basic calcium phosphate and calcium pyrophosphate dihydrate deposition diseases, and, in very rare cases, calcium oxalate crystal arthropathy. These crystals are responsible for different rheumatic syndromes, including acute or chronic synovial inflammation, and also contribute to cartilage degeneration. This review gives an overview of the pathological and clinical changes of these arthropathies.

Perfusion culture system: Synovial fibroblasts modulate articular chondrocyte matrix synthesis in vitro.

OBJECTIVE: To investigate the interactions of chondrocyte metabolism by synovial cells and synovial supernatants in a new perfusion co-culture system. METHODS: Chondrocytes and synovial fibroblasts were obtained from knee joints of slaughtered adult cattle. For experimental studies chondrocytes and synovial fibroblasts were placed together into a perfusion chamber (co-culture) or were placed into two different perfusion culture containers, which were connected by a silicone tube (culturing of chondrocytes with synovial supernatants). A control setup was used without synovial cells. Chondrocyte proliferation was shown by measurement of DNA content. The proteoglycan synthesis was quantified using (35)SO(4)(2-)-labelling and the dimethylmethylene blue assay. (3)H-proline incorporation was used to estimate the protein biosynthesis. Type II collagen synthesis was measured by ELISA, furthermore extracellular matrix deposition was monitored immunohistochemically (collagen types I/II). Regarding to the role of reactive oxygen species LDH release before and after stimulation with hydrogen peroxide was measured. RESULTS: The proliferation of chondrocytes shows an increase in monoculture as well as in co-culture or in culture with synovial supernatants more than fivefold within 12 days. (3)H-proline incorporation as a marker for chondrocytes biosynthetic activity decreases in co-culture system and in culture with synovial supernatants. A similar effect is seen measuring total proteoglycan content as well as the (35)SO(4)(2-) incorporation in chondrocytes. Co-culturing and culturing with synovial supernatants lead to a significant decrease of proteoglycan release and content. Quantification of collagen type II by ELISA shows significant lower amounts of native collagen type II in the extracellular matrix of co-cultured chondrocytes as well as in culture with synovial supernatants. The membrane damage of chondrocytes by hydrogen peroxide is reduced when chondrocytes are co-cultured with synovial fibroblasts. CONCLUSION: The co-culture perfusion system is a new tool to investigate interactions of different cell types with less artificial interferences. Our results suggest that synovial supernatants and synovial fibroblasts modulate the biosynthetic activity and the matrix deposition of chondrocytes as well as the susceptibility to radical attack of reactive oxygen species.

Calcification of articular cartilage in human osteoarthritis.

OBJECTIVE: Hypertrophic chondrocyte differentiation is a key step in endochondral ossification that produces basic calcium phosphates (BCPs). Although chondrocyte hypertrophy has been associated with osteoarthritis (OA), chondrocalcinosis has been considered an irregular event and linked mainly to calcium pyrophosphate dihydrate (CPPD) deposition. The aim of this study was to determine the prevalence and composition of calcium crystals in human OA and analyze their relationship to disease severity and markers of chondrocyte hypertrophy. METHODS: One hundred twenty patients with end-stage OA undergoing total knee replacement were prospectively evaluated. Cartilage calcification was studied by conventional x-ray radiography, digital-contact radiography (DCR), field-emission scanning electron microscopy (FE-SEM), and synovial fluid analysis. Cartilage calcification findings were correlated with scores of knee function as well as histologic changes and chondrocyte hypertrophy as analyzed in vitro. RESULTS: DCR revealed mineralization in all cartilage specimens. Its extent correlated significantly with the Hospital for Special Surgery knee score but not with age. FE-SEM analysis showed that BCPs, rather than CPPD, were the prominent minerals. On histologic analysis, it was observed that mineralization correlated with the expression of type X collagen, a marker of chondrocyte hypertrophy. Moreover, there was a strong correlation between the extent of mineralization in vivo and the ability of chondrocytes to produce BCPs in vitro. The induction of hypertrophy in healthy human chondrocytes resulted in a prominent mineralization of the extracellular matrix. CONCLUSION: These results indicate that mineralization of articular cartilage by BCP is an indissociable process of OA and does not characterize a specific subset of the disease, which has important consequences in the development of therapeutic strategies for patients with OA.

[Crystal arthropathies]. / Kristallarthropathien.

Basic calcium phosphate (BCP) and calcium pyrophosphate dihydrate crystals are the most common types of pathologic crystals, followed by monosodium urate crystals and, in rare cases, calcium oxalate crystals. These crystals have been associated with a variety of quite different rheumatic syndromes. They are responsible for acute synovial inflammation and also contribute to cartilage degradation and bone lesions within the joint. Although understanding of the molecular mechanisms involved in generating the pathologic effects of these crystals has increased, the role of BCP crystals in particular remains poorly understood. The clinical implication of articular deposits of calcium-containing crystals in osteoarthritis is unknown. This review provides an overview of the clinical and pathological changes of these four different types of crystals.

[Synovial chondromatosis]. / Synoviale Chondromatose.

Primary articular synovial chondromatosis is a benign, self-limiting neoplastic process in which hyaline cartilage nodules form in the synovial tissue. The disease most frequently affects the knee in men, followed by the elbow. The basic feature of this disease is a metaplastic maturation of the mesenchymal cells in the synovial membrane of a joint into cartilage. These cells mature into chondroblasts and form small nodules of cartilage in the synovial membrane. These nodules subsequently enlarge and detach to lie within the joint space. They become free within the joint as multiple small cartilaginous loose bodies nourished by the synovial fluid. The chondrocytes in the loose bodies continue to multiply, and the loose bodies grow in diameter. Calcification appears in the central zone of the loose bodies, and in some cases, enchondral ossification takes place. The operative therapy depends on the stage of the disease: synovectomy with removal of chondral fragments if active intrasynovial disease is present, and removal of the multiple chondral bodies alone in cases of late inactive disease with no synovial abnormalities. Malignant transformation is unusual and can be difficult to distinguish from benign disease.

The value of synovial biopsy, joint aspiration and C-reactive protein in the diagnosis of late peri-prosthetic infection of total knee replacements.

We analysed the serum C-reactive protein level, synovial fluid obtained by joint aspiration and five synovial biopsies from 145 knee replacements prior to revision to assess the value of these parameters in diagnosing late peri-prosthetic infection. Five further synovial biopsies were used for histological analysis. Samples were also obtained during the revision and incubated and analysed in an identical manner for 14 days. A total of 40 total knee replacements were found to be infected (prevalence 27.6%). The aspiration technique had a sensitivity of 72.5% (95% confidence interval (CI) 58.7 to 86.3), a specificity of 95.2% (95% CI 91.2 to 99.2), a positive predictive value of 85.3% (95% CI 73.4 to 100), a negative predictive value of 90.1% (95% CI 84.5 to 95.7) and an accuracy of 89%. The biopsy technique had a sensitivity of 100%, a specificity of 98.1% (95% CI 95.5 to 100), a positive predictive value of 95.2% (95% CI 88.8 to 100), a negative predictive value of 100% and an accuracy of 98.6%. C-reactive protein with a cut-off-point of 13.5 mg/l had a sensitivity of 72.5% (95% CI 58.7 to 86.3), a specificity of 80.9% (95% CI 73.4 to 88.4), a positive predictive value of 59.2% (95% CI 45.4 to 73.0), a negative predictive value of 88.5% (95% 81.0 to 96.0 CI) and an accuracy of 78.1%. We found that biopsy was superior to joint aspiration and C-reactive protein in the diagnosis of late peri-prosthetic infection of total knee replacements.

[Periarticular mineralization of the finger]. / Die periartikuläre Mineralisation des Fingers.

Periarticular mineralization is a clinical disorder, which is typically found at the shoulder, knee and hip joint and only rarely diagnosed at the finger joints. Periarticular ossification is a different entity and has to be distinguished from periarticular mineralization. The typical symptoms of this disorder are pain and swelling of the joint that resolves spontaneously within 3-6 months. We report on a case of periarticular mineralization of the metacarpophalangeal (MCP) joint of a 39-year-old woman. Diagnosis was made by X-ray based on findings in the form of opaque mineralizations. There was no pain relief with conservative treatment and operative treatment was performed. Histological and electron microscope analysis of the mineralization showed hydroxyapatite crystals and chondrogenic metaplasia of the surrounding fibroblasts. The patient was symptom-free soon after treatment.Usually, the therapy of the periarticular mineralization is conservative; only exceptional cases with persistent pain and swelling need operative treatment. Acute periarticular mineralization of the hand is rare and often misdiagnosed as infectious arthritis.

Accuracy and precision in the detection of articular cartilage lesions using magnetic resonance imaging at 1.5 Tesla in an in vitro study with orthopedic and histopathologic correlation.

BACKGROUND: Magnetic resonance (MR) sequences for cartilage visualization have been the target of numerous studies, and the optimal sequence for cartilage imaging remains a matter of debate in the literature. PURPOSE: To compare MR findings with different MR sequences for the detection of cartilage lesions in fresh deep-frozen human cadaveric patellae in an in vitro setting. MATERIAL AND METHODS: Ten cadaveric patellae were imaged on a 1.5T MR scanner with a 2x2 channel carotid sandwich coil and a conventional knee coil, and compared with orthopedic findings and gold-standard histopathology. MR sequences were: a) fat-saturated (FS) proton density-weighted (PDw) turbo spin-echo (TSE) sequence (TR/TE 4000/39 ms); b) T2-weighted (T2w) double-echo steady-state (DESS) 3D water-excitation (we) sequence (TR/TE 17/4.7 ms); c) 3D-PDw-SPACE (sampling perfection with application-optimized contrasts using different flip-angle evolutions)-we sequence (TR/TE 1800/19 ms). Accuracy, Kendall's tau-b correlation, and weighted kappa coefficients were calculated. RESULTS: Accuracy for cartilage lesion detection with the FS PDw-TSE sequence and the carotid coil was 78.3%, and with the knee coil 73.9%. For the T2wDESS-3D-we sequence, the corresponding values were 69.5% and 65.2%, and for the 3D-PDw-SPACE-we sequence 65.2% and 60.8%, respectively. Kendall's tau-b correlation ranged between 0.508 for the 3D-PDw-SPACE-we sequence (knee coil) and 0.720 for the FS PDw-TSE sequence (carotid and knee coil). Weighted kappa coefficient was lowest for the 3D-PDw-SPACE-we sequence (knee coil) at 0.607, and highest for the carotid coil and FS PDw-TSE sequence at 0.779. CONCLUSION: The evaluated FS PDw-TSE sequences are superior in comparison to the T2wDESS-3D-we and 3D-PDw-SPACE-we sequences in the in vitro setting for the detection of cartilage lesions, and are comparable to results reported in the literature.

[Principles of fixation of the cementless modular revision stem Revitan]. / Fixationsprinzipien des zementlosen modularen Hüftrevisionsschaftes Revitan. Eine anatomische Studie.

AIM AND METHOD: To analyse the femoral fixation of a modular cementless revision endoprosthesis, eight prosthetic combinations of the Revitan-System (Centerpulse, Winterthur, Switzerland) were implanted in four cadavers. On three cadavers a curved revision Revitan stem was implanted by an endofemoral approach on one side and by a transfemoral approach on the contralateral side. On the fourth cadaver a straight Revitan stem was implanted on one side and a curved Revitan stem on the contralateral side using a transfemoral approach. Transversal slides of 7-8 mm thickness were performed at the fixation areas of each implant and the implant-bone contact was analysed macroscopically and using contact radiography. RESULTS: The straight stem implanted by a transfemoral approach showed a double-conical press-fit fixation with cutting of the eight longitudinal fins into the cortical bone. The curved revision stems implanted by the same approach had a circular surface fixation similar to the press-fit fixation of the straight stem. In contrast, the curved stems implanted by the endofemoral approach (without a window) showed a three-surface fixation. Hereby the two distal fixation areas led to the primary implant stability by three of the four double edges of the octagonal cross-sectional area cutting into the cortical bone. At the proximal fixation zone the implant only had contact of two implant double edges to the cortical bone. CONCLUSION: Different approaches for implantation lead to different fixation techniques of a curved revision stem. This should be considered by analysing postoperative sintering rates of cementless revision stems.

[The value of preoperative knee aspiration and arthroscopic biopsy in revision total knee arthroplasty]. / Die Wertigkeit von präoperativer Punktion und arthroskopischer Synovialisprobenentnahme bei Knietotalendoprothesenwechsel.

AIM: The accurate preoperative diagnosis of occult sepsis in endoprosthetic loosening of total knee arthroplasty is the key to successful management of revision total knee arthroplasties. The aim of this study was to evaluate the results of preoperative aspiration in comparison with preoperative arthroscopic biopsy of the synovial tissue. METHOD: From 2000 to 2004 eighty-six revision total knee arthroplasties in 86 patients were performed. 60 patients had only a knee aspiration, 15 an arthroscopic biopsy and an aspiration, 11 only arthroscopic biopsy. The results of both methods were compared with the intraoperative cultures during revision surgery. RESULTS: 69 aseptic and 17 septic knee exchange arthroplasties were performed. The preoperative aspiration of the prosthetic knee joint had a sensitivity of 68.8 %, specificity of 96.6 %, positive predictive value of 84.5 % and a negative predictive value of 92.2 %. The preoperative arthroscopic biopsy had a sensitivity of 100 %, specificity of 94.7 %, positive predictive value of 87.4 % and a negative predictive value of 100 %. CONCLUSION: Preoperative aspiration of the knee is a very helpful study for the diagnosis or exclusion of infection in a prosthetic knee joint and should be a standard procedure in the diagnosis of prosthetic loosening. If after aspiration a suspicion of infection remains, then the biopsy is an accurate procedure to diagnose or exclude periprosthetic sepsis.

Risk analysis and safety assessment in surgical robotics: a case study on a biopsy robot.

One of the most important issues in medical robotics is safety and integration into the clinical workflow. If a robot is not safe and its use is complicated by difficult handling and complex user interfaces physicians would not use a robotic system during clinical patient trials, whatever the other advantages are. However, there are only few publications on this topic, in particular on risk management in developing a robotic prototype (for clinical trials). In this paper risk management and the safety of using robot-assisted surgery equipment are discussed and demonstrated exemplarily in the process of developing a prototype biopsy robot.

A web implementation: the good and the not-so-good.

E-commerce, e-mail, e-greeting, e-this, and e-that everywhere you turn there is a new "e" word for an internet or Web application. We, at the Cleveland Clinic Foundation, have been "e-nlightened" and will discuss in this report the implementation of a web-based radiology information system (RIS) in our radiology division or "e-radiology" division. The application, IDXRad Version 10.0 from IDX Corp, Burlington, VT, is in use at the Cleveland Clinic Foundation and has both intranet (for use in Radiology) and internet (referring physician viewing) modules. We will concentrate on the features of using a web browser for the application's front-end, including easy prototyping for screen review, easier mock-ups of demonstrations by vendors and developers, and easier training as more people become web-addicted. Project communication can be facilitated with an internal project web page, and use of the web browser can accommodate quicker turnaround of software upgrades as the software code is centrally located. Compared with other technologies, including client/server, there is a smaller roll out cost when using a standard web browser. However, the new technology requires a change and changes are never implemented without challenges. A seasoned technologist using a legacy system can enter data quicker using function keys than using a graphical user interface and pointing and clicking through a series of pop-up windows. Also, effective use of a web browser depends on intuitive design for it to be easily implemented and accepted by the user. Some software packages will not work on both of the popular web browsers and then are tailored to specific release levels. As computer-based patient records become a standard, patient confidentiality must be enforced. The technical design and application security features that support the web-based software package will be discussed. Also web technologies have their own implementation issues.

HIV-related diarrhea is multifactorial and fat malabsorption is commonly present, independent of HAART.

OBJECTIVE: Highly active antiretroviral therapy (HAART) has significantly decreased the incidence of infectious diarrhea affecting HIV-infected patients. Still, diarrhea remains a common symptom in HIV. We sought to determine the incidence of fat malabsorption as a cause of diarrhea in HIV patients receiving non-HAART (nucleoside analog only) and HAART (protease inhibitor-containing) antiretroviral regimens. METHODS: From June, 1995, to April, 1999, 88 HlV-infected patients underwent evaluation for diarrhea, which included endoscopy. We examined the incidence of fat malabsorption with a 24-h stool collection for fecal fat in a cohort of these patients (N = 33). Patients were divided into two groups, those receiving protease inhibitor-containing HAART and those receiving less intensive, nucleoside analog-only, non-HAART regimens. RESULTS: Thirty of 33 patients (90.9%) had fat malabsorption. Twenty of 21 patients not receiving HAART (95.2%) had fat malabsorption with a mean of 34 +/- 38 g of stool fat and a mean stool weight of 797 +/- 454 g. Ten of 12 patients receiving HAART (83.3%) had fat malabsorption with a mean of 46 +/- 86 g of stool fat and a mean stool weight of 800 +/- 647 g. Stool weight correlated with the degree of fat malabsorption (R = 0.77). CONCLUSION: Fat malabsorption represents a commonly undiagnosed entity in HIV-infected patients with diarrhea, whether or not they are receiving HAART therapy. Fecal fat determination should be considered a routine part of the diagnostic workup of HIV-infected patients experiencing diarrhea.

Translocation (3;21;8)(q21;q22;q22) in a patient with acute myeloid leukemia. A case report and review of prognostic indicators.

We report a patient with acute myeloid leukemia (AML) and t(3;21;8)(q21;q22;q22). This translocation has not been previously described in de novo or relapsed AML. The patient is a 25-year-old woman who presented with WBC 6.2 x 10(9)/L, Hgb 10.2 g/dL, Hct 28.4%, and platelets 67 x 10(9)/L. A bone marrow biopsy revealed a 70% hematopoietic cellularity with 65% blasts. Immunophenotyping showed aberrant expression of lymphoid-associated marker CD19. Cytogenetic analysis on a 72-hour culture of bone marrow cells supplemented with conditioned media was evaluated by G-banding at about the 400-band level. The patient's age, cytogenetics, WBC, and immunophenotype at diagnosis would seem to suggest a favorable prognosis, according to previous studies of prognostic indicators. She was treated with induction and consolidation chemotherapy, followed by myeloablative conditioning and autologous peripheral blood stem cell transplant (PBSCT). Despite multiple favorable prognostic factors, the patient relapsed 7 months after PBSCT. Translocation of chromosomes 8 and 21 is common in AML and is generally considered a good prognostic factor. We suspect that the effect of the 3q21 translocation in an otherwise favorable translocation of chromosomes 8 and 21 may be responsible for this patient's early relapse.

Diagnosing and treating onychomycosis.

Onychomycosis is a particular concern for active people because they're exposed to fungi in locker rooms and because hot, sweaty feet enable the infection to flourish. A thorough physical exam and potassium hydroxide exam of debris from the nail plate can help rule out look-alike conditions and provide information that will guide drug therapy. Treatment with the new generation of onychomycosis medications-itraconazole, fluconazole, and terbinafine hydrochloride-is costly but produces impressive cure rates. Active patients need detailed instruction about preventive measures to avoid recurrence.

Comparison of Technetium-99m sestamibi and indium-111 octreotide imaging in a patient with Ewing's sarcoma before and after stem cell transplantation.

BACKGROUND: We report the use of two novel nuclide agents, Technetium-99m (99Tc)sestamibi (MIBI) and indium-111 (In-111) octreotide, in comparison with conventional computed tomography (CT) imaging in a patient with metastatic Ewing's sarcoma (ES) before and after high dose chemotherapy with autologous peripheral stem cell transplantation (PSCT). MIBI is taken up actively by metabolically active tumor cells. Octreotide, a somatostatin analog, binds specifically to somatostatin receptors. METHODS: The patient was a 20-year-old male with recurrent metastatic ES to the lung. Before and sequentially after high dose chemotherapy and PSCT, the patient was imaged with MIBI. Whole body planar and single photon emission computed tomography (SPECT) images were obtained after the injection of 30 mCi of 99Tc MIBI. Prior to PSCT the patient was imaged with 6 mCi In-111 pentreotide. RESULTS: Conventional CT scans also were performed. Initial CT revealed pulmonary metastasis in the right lower lobe along with multiple left pleural-based lesions. These lesions were visualized clearly with MIBI. Octreotide detected only the left lung involvement. Sequential MIBI scans after PSCT correlated with tumor reduction in the right lung field and tumor progression in the left lung as well as the development of new pulmonary metastasis. These findings were confirmed on CT. CONCLUSIONS: MIBI imaging was highly concordant with CT scanning in the detection of metastatic ES. MIBI scanning holds promise for the direct detection of a variety of human malignancies, and may prove useful as a rapid whole body imaging modality.

Skin Necrosis Associated With Heparin-Induced Thrombocytopenia and Thrombosis.

Skin necrosis is a rare complication of heparin therapy. Strong evidence suggests an immune-mediated mechanism in which heparin-antibody complexes bind to platelets, resulting in platelet aggregation, thromboembolism, and ischemic necrosis. Heparin-induced thrombocytopenia (HIT) may also occur in response to immune-mediated platelet aggregation. The presence, of heparin-dependent antibodies can be confirmed by platelet aggregometry, (14)C-serotonin release assay (SRA), or enzyme-linked immunosorbent assay (ELISA). Clinical suspicion, early detection and immediate cessation of heparin therapy are important in preventing the potentially severe complications of heparin-induced platelet aggregation. Potential therapeutic approaches include plasmapheresis and alternative forms of anticoagulation such as warfarin, aspirin, dipyridamole, or other novel investigational agents.