Providing perioperative care for patients with hip fractures.

Providing perioperative care for patients with hip fractures can present major challenges for the anaesthesiologist. These patients often have multiple comorbidities, the deterioration of any one of which may have precipitated the fall. A careful balance has to be achieved between minimising the time before operation and spending time to optimise their medical status. This review will present insights into preoperative patient assessment and optimization in this group of patients from the anaesthesiologists' perspective. In particular, it will highlight important medical issues of concern that may alter anaesthetic risks and management. With a greater understanding of what these issues are, potentially a more prompt and integrated approach to managing these patients may be made. Hopefully, this would result in minimising last minute cancellations due to medical reasons for these patients.

Preoperative cardiac risk assessment in geriatric patients with hip fractures: an orthopedic surgeons' perspective.

Hip fracture is one of the most common orthopedic conditions and is associated with significant morbidity and mortality. With a progressively aging population, the annual incidence of hip fracture is expected to increase substantially. Emerging evidence suggests that early surgery (<24 h) minimizes complications secondary to immobilization, including orthostatic pneumonia and venous thromboembolism. Delayed surgical repair (>48 h) has been consistently demonstrated to be associated with an increased risk of 30-day and 1-year mortality. Nonetheless, early surgery necessitates a shorter time for preoperative medical preparation, in particular cardiac assessment. Patients who undergo emergent orthopedic surgery are therefore at greater risk of perioperative cardiac events than those who undergo elective surgery. In addition, the prompt triage system for preoperative cardiac assessment not only identifies patients at high risk of perioperative cardiac complications but also reduces unnecessary cardiac consultations for low-risk patients. We review the current recommendations for preoperative cardiac assessment adapted for patients with hip fracture and describe our current triage system for preoperative cardiac consultation.

Histological and immunohistochemical characterization of extranodal diffuse large-cell lymphomas with prominent spindle cell features.

AIMS: To describe five cases of diffuse large-cell lymphoma with prominent spindle cell components involving skin, nasal-ocular mucosa, and soft tissue. Because of the spindle cell morphology, such cases must be differentiated from true sarcomas arising in or metastasizing to soft tissue, skin, bone, lymph node, or other organs and sites. METHODS AND RESULTS: Formalin-fixed paraffin-embedded archival tissue from five consultation cases of diffuse large-cell lymphoma with prominent spindle cell features involving the skin, nasal-ocular mucosa, and soft tissue in three male and two female patients was studied by histology and immunohistochemistry. Clinicopathological findings were also reviewed for all the patients. By morphology, initial evaluation of the cases suggested spindle cell sarcoma in two cases, inflammatory pseudotumour in one case, large-cell lymphoma in another case, and one case was considered suspicious for malignant lymphoma. Immunohistochemistry demonstrated a B-cell lineage in four of the spindle cell lesions, with a diagnosis of primary cutaneous CD30+ anaplastic large cell lymphoma made for the fifth case. Four of five cases also showed actin reactivity. CONCLUSIONS: Although extremely rare, lymphomas with prominent spindle cell morphology can be encountered in daily surgical pathology practice, and should be included in the differential diagnosis of spindle cell lesions in skin and soft tissue. The observed actin reactivity in four of the five spindle cell lymphomas may lead to a misdiagnosis of leiomyosarcoma if lymphoid markers are not included in the immunohistochemical panel.

[Preparation and evaluation of phosphatidylcholine coated on silica as the biomembrane stationary phase].

The method of reverse phase evaporation is used to coat phosphatidylcholine(PC) directly on the surface of silica, which is used as biomembrane chromatographic solid phase to study the interactions between drugs and biomembrane. It was observed that the solid phase coated phosphatidylcholine had a good stability at 20 degrees C-30 degrees C, and the stability would be improved by the presence of appropriate amount of cholesterol in phosphatidylcholine. The content of cholesterol in phosphatidylcholine, the nature of buffer, the concentration of salt in buffer and the pH of mobile phase could all affect chromatographic retention of drugs on the prepared biomembrane column. Six compounds, polyethylene glycol, mannitol, salicylic acid, warfarin, hydrocortisone, and cortisone have been tested. The biomembrane chromatographic stationary phase coated PC with silica as matrices can be simply prepared and it is possible to simulate the human's physiological environment by the biomembrane chromatographic system, so it is a useful method to study drug absorption and distribution in human body.

Sinonasal NK/T-cell lymphomas in the United States.

Sinonasal natural killer (NK)/T-cell lymphomas are common in Asia and areas of South and Central America but are rarely seen in the United States, where they have not been as well characterized. Fifteen cases diagnosed in Southern California were studied with respect to histologic features, immunophenotype, Epstein-Barr virus EBER in-situ hybridization (EBV EBER-ISH), and T-cell receptor gamma chain (TCR-gamma) gene rearrangement. Although ethnic background was available for only seven patients, six were of Asian or Hispanic descent with only one non-Hispanic white known. Twelve presented as sinonasal lesions, but three were limited to the oropharynx. Most cases (11 of 15) demonstrated both necrosis and an angiodestructive pattern. All cases demonstrated cytoplasmic CD3 positivity (15 of 15), and were positive for both TIA-1 and granzyme B (14 of 14). Perforin was positive in 5 of 14. CD56 was expressed in 10 of 15 and CD8 in 3 of 15. EBV EBER-ISH was positive in 14 of 14 and TCR-gamma gene rearrangement was detected in 1 of 14 cases. None (0 of 14) were positive for CD16 or CD57. Although CD16-positive histiocytes were abundant, double-label EBER-ISH/IHC failed to identify CD16 expression on EBV-positive tumor cells. Three cases with pleomorphic large cell morphology showed focal CD30 positivity, raising the differential diagnosis of anaplastic large cell lymphoma, but all were ALK-1-negative and otherwise similar to the other cases of NK/T-cell lymphoma. Sinonasal NK/T-cell lymphomas in the United States most often occur in ethnic groups from areas of reported high frequency (Asia, Central and South America), although less commonly than in endemic populations, and are otherwise similar phenotypically. A combined approach, including immunohistochemistry, EBV EBER-ISH, and TCR gene rearrangement studies, is most helpful to arrive at the correct diagnosis.

Primary T-cell-rich B-cell lymphoma of the ethmoid sinus. A case report with 5 years of follow-up.

T-cell-rich B-cell lymphoma (TCRBCL) is an uncommon and recently recognized variant of B-cell non-Hodgkin lymphoma characterized by a few large neoplastic B cells amid a predominant population of reactive T lymphocytes and variable numbers of histiocytes. Morphologically, TCRBCL resembles a variety of non-Hodgkin lymphomas and Hodgkin disease. Accurate diagnosis and proper treatment are essential to assure a favorable prognosis. To our knowledge, this is the first report of ethmoid sinus presentation of TCRBCL in an Epstein-Barr virus-negative 51-year-old man. Combined chemotherapy and radiotherapy were administered based on the correct diagnosis. The patient has had a complete response with no recurrence during the 5-year follow-up.

Using fluorescence-based human androgen receptor gene assay to analyze the clonality of microdissected dendritic cell tumors.

The clonality of dendritic cell proliferations arising in patients with previously diagnosed B-cell non-Hodgkin lymphoma has not been determined. The highly polymorphic human androgen receptor gene (HUMARA) can be used to assess the pattern of X-chromosome inactivation and, hence, the clonality of tumors in female patients. In this study, specimens from 2 female patients with dendritic cell tumor following low-grade B-cell non-Hodgkin lymphoma were analyzed. Microdissection was performed on tissue sections to obtain representative tissues for analysis. The HUMARA polymerase chain reaction was modified to include a fluorochrome (6-carboxyfluorescein)-labeled primer so the product could be assessed with the ABI Genescan Analysis program for the Macintosh (Applied Biosystems, Foster City, Calif). Our results indicate that dendritic cell proliferations associated with low-grade B-cell non-Hodgkin lymphoma are clonal lesions. Previous microdissection is very helpful in obtaining the desired cell populations for study. The use of a fluorescent primer coupled with the Genescan System is a novel, highly sensitive, quantitative system that avoids the use of radioactive materials.

Isolated leptomeningeal Castleman's disease with viral particles in the follicular dendritic cells.

To our knowledge, five cases of Castleman's disease involving only the central nervous system have been reported previously. We report a sixth case, which occurred in a 47-year-old woman with a 3-month history of headaches and a large superior frontal lobe mass on neuroimaging. Excisional biopsy revealed confluent lymphoid nodular areas with multiple well-developed germinal centers surrounded by concentrically layered proliferations of small B lymphocytes typical of Castleman's disease. Ultrastructural study found 100-nm virallike particles within follicular dendritic cells as well as intercellular spaces. These particles were suggestive of a D-type retrovirus. The patient underwent postoperative radiotherapy and was neurologically normal 3 months after surgery.

Expression of the cell-cycle-related proteins E2F-1, p53, mdm-2, p21waf-1, and Ki-67 in multiple myeloma: correlation with cyclin-D1 immunoreactivity.

Approximately 30% of multiple myelomas (MMs) express cyclin D1 when assessed using immunohistochemical techniques. Cyclin D1 expression correlates with greater tumor burden in MM, because cyclin D1-positive cases are more frequently associated with extensive bone marrow involvement, i.e., high pathologic stage, than are cyclin D1-negative cases. The mechanisms that explain this association are unknown. To explore other differences between cyclin D1-positive and cyclin D1-negative MMs, we assessed 59 MMs immunohistochemically for several G1 cell-cycle regulatory proteins, including cyclin D1, E2F-1, p53, mdm-2, and p21waf-1, using routinely fixed and processed, paraffin-embedded bone marrow specimens. Twenty MMs (34%) were cyclin D1 positive, and 39 (66%) were cyclin D1 negative. Eighteen (90%) of 20 cyclin D1-positive MMs were Stage III, in contrast to 19 (49%) of 39 cyclin D1-negative MMs (P = .003). Cyclin D1-positive MMs were more likely to express E2F-1 (16/20 vs. 4/39, P < .001), p53 (11/20 vs. 10/39, P = .041), and p21waf-1 (12/20 vs. 7/39, P = .003). There was no significant difference in mdm-2 expression between these groups. We also assessed proliferation rate using an antibody specific for the Ki-67 antigen. A relatively high percentage (> 20%) of Ki-67-positive cells was found in cyclin D1-positive MMs compared with cyclin D1-negative MMs (13/20 vs. 3/39, P < 0.001). These results suggest that cyclin D1-positive MMs are more likely to possess additional derangements involving other G1 cell-cycle regulatory proteins. We speculate that these abnormalities might result in increased proliferation, thereby explaining the correlation between cyclin D1 expression and greater tumor burden.

Clinically silent primary adrenal lymphoma: a case report and review of the literature.

Primary adrenal lymphoma (PAL) is extremely uncommon. We describe a case of clinically silent non-Hodgkin's B-cell lymphoma of diffuse large cell type with exclusive left adrenal localization. The tumor was discovered by computed tomography (CT) as a 2.5-cm dense mass and diagnosed at autopsy. Literature concerning this unusual neoplasm is reviewed. During the early stage, particularly when the lesion is small, PAL is likely to be missed. This unusual entity should be included in the differential diagnosis of adrenal masses so that early diagnosis may be made and intervention might dramatically affect the clinical outcome.

Heterogeneity of macrophage and T cell subpopulations in peripheral nerves from HIV infected individuals: A preliminary study.

GOAL: To determine the heterogeneity of surface marker expression of macrophages in peripheral nerve of patients who died with AIDS. BACKGROUND: Peripheral neuropathy occurs in 20%-40% of AIDS patients. There is evidence that activated macrophages may be involved in the neural damage associated with HIV-1 infection. We studied the expression of macrophage surface markers CD14, CD11c, CD68, and HLA-DR and also T cell surface markers CD3, CD4, and CD8 in peripheral nerves of AIDS patients. METHODS: Three levels of peripheral nerves (sciatic, tibial, or sural) were examined from a limited number of subjects consisting of 4 HIV-seropositive and 5 HIV-seronegative individuals. Standard immunohistochemical technique utilized alkaline phosphatase conjugate and fuchsin substrate. RESULTS: Surface antigen expression was significantly (p < .0025 increased in HIV-positive tissues compared with HIV-negative controls for CD14 and CD4 in sciatic nerves, CD68 and CD4 in tibial nerves, and CD68 in sural nerves. There were trends for increased expression of HLA-DR, CD3, and CD8 in sciatic nerves, CD11c and CD14 in tibial nerves, and CD14, HLA-DR, and CD4 in sural nerves in HIV-positive tissues compared with HIV-negative controls. CONCLUSION: During the course of AIDS there may be an involvement of all three levels of peripheral nerves suggesting that HIV-related neuropathy is a multifocal process.

Cyclin D1 protein in multiple myeloma and plasmacytoma: an immunohistochemical study using fixed, paraffin-embedded tissue sections.

In this study, we analyzed 69 plasma cell neoplasms, including 54 multiple myelomas (MMs), 3 cases of plasma cell leukemia, and 12 plasmacytomas, for expression of cyclin D1 protein using an immuno-histochemical method applied to routinely fixed, paraffin-embedded tissue sections. Cyclin D1 was expressed in 18 (26%) of 69 plasma cell neoplasms, including 16 (30%) of 54 MMs and 2 (17%) of 12 plasmacytomas. Three cases of plasma cell leukemia were negative. Cyclin D1 expression correlated with the cytologic differentiation and histologic stage of MM. Twelve (75%) of 16 MMs had intermediate or immature cytologic features and were histologic Stage III. With use of a polymerase chain reaction assay, we also analyzed six cases (three cyclin D1 positive, three cyclin D1 negative) for the t(11;14); one MM carried the t(11;14) and expressed cyclin D1 protein. We conclude that cyclin D1 expression occurs in approximately one-quarter of plasma cell neoplasms and correlates with the degree of cytologic differentiation and histologic stage. The relatively high frequency of cyclin D1 expression, compared with the less than 5% incidence of the t(11;14) detected by conventional cytogenetics reported in the literature, suggests that upregulation of cyclin D1 protein might be the result of mechanisms other than the t(11;14).

Concurrent thrombotic thrombocytopenic purpura and immune thrombocytopenic purpura in an HIV-positive patient: case report and review of the literature.

Immune thrombocytopenic purpura (ITP) and thrombotic thrombocytopenic purpura (TTP) have each been associated with HIV infection. Sequential occurrence of these two diseases with a disease-free interval has been occasionally reported in the literature, whereas simultaneous manifestations of these two diseases have not been described. Here, we report an AIDS patient who was initially diagnosed as having TTP and showed an apparent partial response to plasmapheresis but was found to have a clinical course similar to ITP. Although precise mechanisms for the development of TTP and ITP in these patients are unclear, we offer several hypotheses. It is important to recognize that these two processes may be seen concurrently.

Dendritic cell tumors associated with low-grade B-cell malignancies. Report of three cases.

Indeterminate and interdigitating cell tumors are rare proliferations of immunoregulatory cells that demonstrate morphologic, immunologic, and ultrastructural features similar to their cells of origin. Although an association of lymphoproliferative disease with Langerhans' cell histiocytosis is well described, only sporadic cases of non-Langerhans' dendritic cell proliferations have been published. The authors describe three patients with low grade B-cell lymphoproliferative disease who developed subsequent indeterminate cell or interdigitating cell tumors. When the two cases of indeterminate cell tumor are added to those previously described in the literature, it appears that 4 of 13 cases (31%) are associated with a history of low grade B-cell malignancy. Possible explanations for the relationship between these two disorders are discussed.

Trisomy 12 in Richter's transformation of chronic lymphocytic leukemia.

Conventional cytogenetic data and fluorescence in situ hybridization (FISH) interphase cytogenetic studies have shown that trisomy 12 is found in many cases of B-cell chronic lymphocytic leukemia (B-CLL). Several reports indicate that +12 is an acquired numerical cytogenetic abnormality, and may be associated with a worse prognosis or more extensive disease. Wright-Giemsa-stained blood or bone marrow smears obtained after initial diagnosis, and subsequent lymph node cells, bone marrow aspirate smears, or effusions were retrospectively studied from five patients whose disease underwent morphologic transformation from typical B-CLL to a high grade lymphoproliferative disease (Richter's syndrome). Using an alpha-satellite DNA probe to the centromere of chromosome 12, trisomy 12 was found in a proportion of cells from all five specimens with high grade lymphoproliferative disease, but in only one of five samples collected before transformation. These data suggest that +12 is an acquired cytogenetic abnormality in CLL and has a high frequency in Richter's syndrome. Because only a subpopulation of the neoplastic cells contain an extra copy of chromosome 12, it is unlikely that this numerical abnormality plays a direct role in transformation to high grade lymphoproliferative disease.

T-cell-rich B-cell lymphoma. A clinicopathologic study of eight cases.

Although T-cell-rich B-cell lymphoma (TCRBCL) is a recently recognized form of non-Hodgkin's lymphoma (NHL), limited information regarding its incidence, cellular origin, morphologic spectrum, and biologic behavior is currently available. In this study, the clinicopathologic features of eight patients with TCRBCL are presented. This neoplasm comprised about 1% of all NHLs seen at Emory University Hospital over 2 years. The male-to-female ratio was 1.6, and the mean age at diagnosis was 60 years. At presentation, TCRBCL was nodal in 88% of the patients and widely disseminated in 50% of the patients. A complete remission was seen in three of the five patients treated with combination chemotherapy that was directed at intermediate grade NHL. Three patients received inadequate or incomplete chemotherapy. One of these patients later achieved a complete remission with more intensive therapy. Two of the patients were not evaluable for response to therapy. The actuarial and disease-free survival rates of the group at 5 years were 72% and 21%, respectively. Morphologically, the lymph nodes in seven of eight cases were diffusely obliterated, whereas one had markedly expanded interfollicular zones that lead to an initial diagnosis of T-zone lymphoma. All tumors were characterized by no more than 25% large lymphoid cells, which were scattered in a background of small lymphocytes with round or irregular nuclei. The presence of numerous histiocytes imparted a lymphoepithelioid appearance in two cases. Although immunoperoxidase stains of frozen tissue were initially suggestive of a peripheral T-cell lymphoma in some cases, paraffin immunoperoxidase stains clearly established the B-cell nature of the large cells, whereas most of the small cells were T lymphocytes. The clonal nature of the large cells was confirmed in seven cases by monotypic immunoglobulin (Ig) light chain restriction or Ig gene rearrangements. Epstein-Barr virus genomic DNA was detected in two of the six cases tested by polymerase chain reaction or Southern blot analysis, but no evidence of a bcl-2 rearrangement was found in any of the five cases examined. These findings indicate that TCRBCL is an uncommon form of NHL with a therapeutic response and overall survival consistent with intermediate grade lymphoma. Paraffin immunoperoxidase stains and occasionally genotypic analysis are required to exclude the diagnosis of PTCL or diffuse lymphocyte predominant Hodgkin's disease. The authors found no morphologic or molecular evidence to support a follicular center cell origin in these cases of TCRBCL.

HIV-1 heterogeneity and cytokines. Neuropathogenesis.

Mild manifestations (HIV-1 associated minor cognitive/motor disorder), severe manifestations (HIV-1 associated dementia complex and HIV-1 associated myelopathy), and sensory neuropathy are consequences of HIV-1 infection. Our goal is to elucidate the role of HIV-1 in the complications of AIDS including cytokine immunopathology and HIV-1 DNA sequence variants. We have examined the brain and sensory ganglia from 60 AIDS patients and 20 seronegative controls using PCR, DNA sequencing of the HIV-1 envelope protein (env), in situ hybridization (ISH), and immunohistochemistry (IHC). Using our combined ISH-IHC technique, we could identify different types of cells and HIV-1 simultaneously in cryostat and paraffin sections. We found HIV-1 predominantly in macrophage/microglia in brain. In dorsal root ganglia (DRG) we found rare macrophages infected with HIV-1 and neurons and interstitial cells (including macrophages) which were apoptotic. Cytokines were detected in mononuclear and endothelial cells near neurons. We achieved single copy sensitivity detecting HIV-1 in nervous tissue using nested PCR. We sequenced HIV-1, DNA from 3 intravenous drug users (IDUs): from brain, CSF, and blood. PCR amplification was followed by cloning and then sequencing the HIV-1 insert: V1-V5 regions of the envelope (env) gene. We found that the env genes had increased sequence variation compared to the literature, cDNA sequences derived from RNA were less heterogeneous than clones derived from DNA from the same specimens, clones derived from brain are more closely related (show restricted heterogeneity) compared to clones from blood and CSF from the same patients. Patient 149 clones we examined to date did not correspond to any of the designated subtypes (A-F) of HIV-1 based on the DNA sequences of the C2-V3 regions. Finally, the HIV-1 RNA produced in these tissues is derived from a minority of DNA clones. Although HIV-1 infected macrophages are not entirely responsible for pathology in the brain and less so in sensory ganglia, some of the products of infection, cytokines, are more widespread in these tissues. Furthermore, HIV-1 strains infecting the brain appear to exhibit restricted heterogeneity compared to autologous CSF and blood and these strains may be associated with cytokines and pathology. HIV-1 strains that infect nervous tissue and cytokines produced in this tissue may effect neuropathogenesis, in vivo, in spite of low levels of local HIV-1 infection. We attempt to delineate, here, common sequence variations in HIV-1 isolates in the hope of developing future therapeutic strategies.

The white IRIS leukocyte differential analyzer for rapid high-precision differentials based on images of cytoprobe-reacted cells.

Combining unique cytoprobe, rapid hemacyte fractionation, and novel color image analysis, The White IRIS (TWI) extends automated intelligent microscopy to leukocyte differentiation. TWI provides flow cytometry precision and microscopical resolution to review specimens flagged by hematology analyzers with differential capabilities or to complement other analyzers without these capabilities. The system includes compartments for closed sampling, rapid leukocyte-rich plasma preparation, cytoprobe-induced metachromasia, and collection and color analysis of leukocyte images, and presents the results as a single-view 500-cell differential on a 20-in. (50-cm) touch-screen monitor. Method correlations for the five mature cell types averaging r > 0.90 were obtained with a prototype system. Classification of normal and abnormal specimens showed 95% agreement with a reference method without any undetected significant morphologic abnormality. False-positive and false-negative rates of 7.27% and 3.53%, respectively, exceeded performance of current commercial systems. Case studies demonstrate the ease and speed with which unusual pathologies and leukemias can be observed and interpreted.