The combined measurement of synovial markers in the diagnosis of periprosthetic joint infection.

INTRODUCTION: Currently there is no single test for periprosthetic joint infection (PJI) that demonstrates an acceptable level of sensitivity. The aim of this pilot study was to identify a combination of biomarkers that could exclude periprosthetic infection prior to revision surgery in hip and knee arthroplasty. This would help in equivocal cases of PJI, such as those with low-virulence organisms, chronic low-grade infection or 'aseptic' loosening. Current research has focused on measuring the levels of biomarkers in the patient's synovial fluid, and these can be combined to improve accuracy. METHODS: We selected synovial white cell count (SF-WCC) and C-reactive protein (SF-CRP), as they demonstrated an acceptable level of sensitivity and specificity which could be measured using existing equipment. One hundred and sixty-one synovial fluid samples from 134 patients were collected and analysed prospectively using calculated cut-off values of 10mg/l for SF-CRP and 3,000×106/l for SF-WCC. Samples were deemed positive for infection when either of the SF-CRP or SF-WCC values were above the cut-off. RESULTS: The combined test demonstrated a sensitivity greater than 98.5% and specificity above 80% in all samples analysed or looked at separately for total hip replacement and total knee replacement infections. All ten aspirates taken from chronically infected joints tested positive. CONCLUSIONS: The combination of SF-CRP and SF-WCC measurement has been shown to have high sensitivity of over 99% in detecting both acute and chronic PJI in both hip and knee arthroplasty. This ability of the test to exclude infection with a high degree of certainty will help in preoperative planning of PJIs.

Erythropoietin response in anaemic patients with multiple myeloma and other lymphoid malignancies infiltrating the bone marrow.

Immunoreactive erythropoietin levels were measured in 42 patients with lymphoid malignancies with anaemia and bone marrow involvement. Results were compared to a control group of 16 patients suffering from anaemia due to other causes. Significant inverse correlations between serum erythropoietin level and haemoglobin concentration were shown for the patients with lymphoid malignancies and also for the control subjects. Overall, the erythropoietin levels of patients with lymphoid malignancies with bone marrow infiltration and with normal renal function did not differ significantly from erythropoietin levels of the anaemic controls. We conclude that anaemia in patients with lymphoproliferative disorders with bone marrow infiltration and normal renal function is caused primarily by a diminished/inadequate response to erythropoietin at the level of the target cell.

Intravascular Hemolysis in Aerobic Dancing: The Role of Floor Surface and Type of Routine.

In brief: The effect of aerobic dancing on intravascular hemolysis was studied in 65 healthy women (aged 18 to 50 years) who were assigned to one of four groups according to the type of routine performed and the hardness of the floor surface. All subjects participated in a 60-minute dance session; a subgroup participated in five successive 60-minute sessions with one hour of rest between sessions. Blood was tested for both groups before and after exercise; urine was tested similarly for the subgroup only. The findings indicated that intravascular hemolysis occurred and that it was influenced by the type of routine, hardness of the surface, and duration of dancing. However, the degree of hemolysis was small and unlikely to contribute to the development of anemia.

Periodontal manifestations of acute autoimmune thrombocytopenic purpura. A case report.

Purpuric hemorrhages are usually the result of thrombocytopenia, but are also seen in vascular disorders such as vitamin C deficiency, Henoch-Schonlein purpura, and von Willebrand's disease. The progressive purpuric hemorrhages in the oral mucosae and skin in a case of acute autoimmune thrombocytopenic purpura (AITP) in a young adult are described. Localized hemorrhagic periodontal lesions of doubtful interpretation proved to be the first clinical signs of the underlying thrombocytopenia. The diagnosis is confirmed by finding thrombocytopenia with normal or increased numbers of megakaryocytes in the bone marrow. Treatment must be started before the onset of serious complications such as cerebral hemorrhages.

The incidence, type, and subsequent evolution of 14 variant Ph1 translocations in 180 South African patients with Ph1-positive chronic myeloid leukemia.

A Philadelphia (Ph1) chromosome translocation was found in 180 of 198 cases of chronic myeloid leukemia (CML). A standard t(9;22) was present in 166 patients, 83 of whom were black, 79 white, and 4 of "mixed" ancestry; whereas a variant Ph1 translocation was detected in 14 patients (7.8%), 11 of whom were black and only 3 white. There was a higher frequency of a variant Ph1 among black patients compared with whites. The significantly higher frequency of a variant among our patients compared with surveys from elsewhere could be due to differing environmental agents. Simple variants were detected in four patients. Complex variants were found in eight cases; in one of these patients, only chromosomes #9 and #22 were involved, but a complex rearrangement of chromosome #9 had occurred. A "masked" Ph1 translocation was detected in two cases, both of which showed monosomy #22 because the Ph1 chromosome was incorporated or interchanged with chromosome #9. Karyotypic evolution of the Ph1-positive cell line was observed more frequently in the variant group (71.4%) than the standard group (29.5%). This difference was significant (p less than 0.005). There was no difference in the type of clonal changes seen in standard and variant groups. The majority of clonal changes were observed during the acute stage in both groups. In the variant group, there was no obvious correlation between the type of variant, type of clonal change, blast morphology, or survival. Their initial survival pattern resembled that of Ph1-negative cases, but those patients who survived longer than 1 year showed a survival trend similar to standard Ph1-positive cases. Possible explanations for the specificity of chromosome #22 involvement and the constancy of the 22q11 breakpoint in all these variant translocations are discussed.

Karyotype analysis in acute nonlymphocytic leukemia (ANLL): comparison with ethnic group, age, morphology, and survival.

The karyotype, leukemia cell morphology (FAB classification), ethnic group, age, sex, and survival were compared in 60 patients with acute nonlymphocytic leukemia (ANLL), to determine their diagnostic and prognostic significance. An ethnic age difference was observed; a significantly greater number of black patients were children. The majority of children were males. A higher frequency of chromosome abnormalities was detected in children, yet they survived longer than adults. A specific, significant association between a (8; 21) karyotype and M2-ANLL was confirmed; four of ten patients with M2-ANLL showed this translocation. The more mature morphology of M2-ANLL was associated with a longer survival irrespective of karyotype, ethnic group, and age. The specificity of t(15; 17) in M3-ANLL and nonrandom monosomy 7 in preleukemic children was confirmed. Patients, particularly adults, with normal karyotypes tended to survive longer than those with abnormal karyotypes. The patient's age and the differentiative capacity of the leukemic cell appear to be as important as the karyotype in determining survival. The nonrandom association of certain chromosome aberrations in ANLL appears to be worldwide.

Evidence for a multistep pathogenesis of chronic myelogenous leukemia.

To study the relationship of the Philadelphia chromosome (Ph1) to the pathogenesis of chronic myelogenous leukemia, multiple B-lymphoid cell lines were established from a patient with Ph1-positive leukemia who was heterozygous for the X-chromosome-linked enzyme glucose-6-phosphate dehydrogenase. Both A and B types of enzyme were found in a 1:1 proportion in normal tissues, but 45 of 63 (71%) Ph1-negative B-lymphoid cells lines derived from this patient showed only the single glucose-6-phosphate dehydrogenase (type B) found in the Ph1-positive leukemic clone. Furthermore, 8 of 33 analyzable lines with B-type enzyme had chromosomal aberrations compared to 0 of 14 lines with A-type glucose-6-phosphate dehydrogenase. These results provide evidence for the suggestion that some cells of the abnormal clone do not express the Ph1 abnormality. Thus, acquisition of Ph1 may not be a sufficient cause for the disease. It is possible that at least two steps are involved in the pathogenesis of Ph1-positive chronic myelogenous leukemia, one causing abnormal proliferation of a clone of pluripotent hematopoietic stem cells and the other inducing Ph1 in descendants of these progenitors.

Establishment of a lymphoid cell line from leukemic cells of a patient with chronic lymphocytic leukemia.

Two lymphoid cell lines were established from a patient with chronic lymphocytic leukemia by infecting blood cells with Epstein-Barr virus (EBV). Studies of morphology, glucose-6-phosphate dehydrogenase, malic enzyme, immunoglobulin, and chromosomes of the two lines indicated that one of them originated from leukemic cells while the other arose from residual normal blood cells. The morphology and capacity for immunoglobulin secretion in the line that arose from leukemic cells were similar to those found in EVB-carrying lymphoblastoid cell lines grown from patients without neoplasia and differed from those seen in fresh chronic lymphocytic leukemia cells. These observations suggest that the introduction of EBV into the leukemic cells may have caused them to differentiate in a fashion similar to that noted in normal B cells after exposure to EBV.

Chromosome analyses of lymphoid cell lines derived from patients with chronic lymphocytic leukemia.

To study chromosome complements of chronic lymphocytic leukemia cells, six Epstein-Barr virus-transformed lymphoid lines were established from two patients with this disease who were heterozygous for the X-chromosome-linked enzyme glucose-6-phosphate dehydrogenase (G6PD). Immunoglobulin and G6PD were used as markers of the leukemic versus normal cell origin of the cell lines. The two lines, derived from putative normal cells, had no chromosomal changes. In contrast, chomosome abnormalities were found in each of the four cell lines of presumed leukemic cell origin. Although the chromosome aberrations are not as specific as the Philadelphia chromosome, there appears to be non-random involvement in chronic lymphocytic leukemia of some chromosomes, such as the No. 12.

Involvement of the B-lymphoid system in chronic myelogenous leukaemia.

Studies with glucose-6-phosphate dehydrogenase (G6PD) isoenzymes have demonstrated that chronic myelogenous leukaemia (CML) is a clonal disorder of pluripotent haematopoietic stem cells which are capable of differentiation to myeloid cells, monocytes, erthrocytes and platelets. It has been observed recently in G6PD heterozygous patients with chronic phase CML that the non-E-rosetting lymphocytes were restricted to a single enzyme type, indicating that some lymphoid cells must also arise from the leukaemic clone. Surface or cytoplasmic immunoglobulin could be detected in up to 46% of the cells of these isolated non-T-lymphocyte populations, which suggested that cells from the CML clone were capable of differentiating into B lymphocytes. To investigate this further, we established Epstein-Barr virus (EBV)-transformed B-lymphoblastoid cell lines derived from patients with CML and studied chromosomes and G6PD to determine whether progenitor B lymphocytes for any of the cell lines had originated from the CML clone. We report here direct evidence that immunoglobulin-synthesizing B lymphocytes can arise from the CML stem cell clone.

Haemolytic anaemia associated with glucosephosphate isomerase (GPI) deficiency in a Black South African child.

Haemolytic anaemia in a Black South African child was found to be associated with reduced glucosephosphate isomerase activity in the red cells. Apart from the haemolytic anaemia, there was no other clinical evidence of dysfunction. Family studies pointed to an autosomal recessive mode of inheritance, with the symptomatic homozygous propositus having a marked enzyme deficiency and the asymptomatic heterozygotes showing intermediate levels of activity. Biochemical characterization showed that, apart from being thermolabile, the electrophoretic mobility and the kinetic properites of the variant enzyme were similar to those of the normal wild type.