Early complications after one hundred and forty-four consecutive hip revisions with impacted morselized allograft bone and cement

BACKGROUND: The use of impacted morselized allograft bone and cement in hip revision arthroplasty has been popular, but studies that specifically address intraoperative and postoperative complications have been scarce. METHODS: All complications that occurred during, and within the first year after, 144 consecutive hip revision arthroplasties (108 stems and 130 sockets) performed with impacted morselized allograft bone and cement were recorded. Clinical and radiographic follow-up evaluation was performed at three months and at one year after surgery for all patients except eight (seven who had died of causes unrelated to the hip surgery and one who had sustained a stroke). Of these eight patients, seven had a six-week and/or three-month follow-up evaluation. RESULTS: Thirty-nine femoral fractures occurred in thirty-seven hips; twenty-nine of the fractures occurred during surgery and ten, within five months after surgery. Of the intraoperative femoral fractures, twelve were proximal, nine were diaphyseal, and eight involved the greater trochanter. Of the postoperative femoral fractures, one was proximal and nine were diaphyseal. Other intraoperative complications were the creation of a femoral cortical window in seven hips and incidental perforation of the femoral cortex in fourteen. Multivariate analysis showed the risk factors for femoral fracture during or after revision to be concomitant disease, greater deficiency of the femoral bone stock, and an intraoperative femoral window or perforation. Other complications included dislocation of the femoral head in nine hips, deep infection in one hip, persistence of preoperative deep infection in one hip, and superficial wound infection requiring wound débridement in two hips. CONCLUSIONS: We found the complication rate to be high after hip revision arthroplasty performed with impacted morselized allograft bone and cement. The most serious complication was postoperative diaphyseal femoral fracture.     

Decreased serum levels of clara cell secretory protein (CC16) are associated with bronchiolitis obliterans and may permit early diagnosis in patients after allogeneic stem-cell transplantation

BACKGROUND: Bronchiolitis obliterans (BO) is a common complication and is associated with high mortality after allogeneic stem-cell transplantation (SCT). Early diagnosis of BO may improve outcome. Low levels of Clara cell secretory protein (CC16) have previously been associated with BO in lung transplant recipients. METHODS: Serum samples were collected from eight patients with BO, eight patients with chronic graft-versus-host disease (GVHD), and eight control patients with neither BO nor chronic GVHD in a matched patient analysis. Patients were matched for diagnosis, conditioning, donor match, and GVHD prophylaxis. Another seven patients with BO were also analyzed separately. CC16 was measured with an enzyme-linked immunosorbent assay method. RESULTS: In the matched analysis, eight patients were diagnosed with BO at a median of 11.5 months (range, 4-13 months) after SCT and in non-matched BO patients at a median of 12 months (range, 9-36 months). In the matched patient analysis, patients with BO had significantly lower (P=0.03) or decreasing (P=0.02) levels of CC16 compared with patients with only chronic GVHD or controls. In the matched patient analysis, measurement of CC16 showed a sensitivity of 88% and a specificity of 81%.With the criteria of low levels of CC16 or a decrease of more than 40% compared with the previous sample, BO was detected with analysis of CC16 in 13 of 15 patients. In 11 of the 13 patients, low or decreasing values of CC16 were detected at a median of 10 months (range, 1-30 months) before BO was diagnosed clinically. CONCLUSIONS: Low levels of CC16 are associated with BO after allogeneic SCT. Monitoring of CC16 in serum after SCT may have potential as an early marker for BO.     

Cellular uptake of radioiodine delivered by trastuzumab can be modified by the addition of epidermal growth factor

Purpose The purpose of this study was to analyse whether non-radiolabelled epidermal growth factor (EGF) can modify the cellular uptake of ¹²⁵I when delivered as [¹²⁵I]trastuzumab. ¹²⁵I was used as a marker for the diagnostically and therapeutically more interesting isotopes ¹²³I (SPECT), ¹²⁴I (PET) and ¹³¹I (therapy).Methods The cell-associated radioactivity was measured in squamous carcinoma A431 cells following addition of [¹²⁵I]trastuzumab. Different concentrations of [¹²⁵I]trastuzumab and unlabelled EGF were used, and the total, membrane-bound and internalised radioactivity was measured. We also analysed how EGF and trastuzumab affected the cell growth. Results It was generally found that the cellular ¹²⁵I uptake was decreased by the addition of EGF when [¹²⁵I]trastuzumab was added for short incubation times. However, if the incubation times were longer, EGF increased the ¹²⁵I uptake. This shift came earlier when higher [¹²⁵I]trastuzumab concentrations were applied. The addition of EGF also influenced cell proliferation, and concentrations above 10 ng/ml reduced cell growth by approximately 20% after 24 h of incubation.Conclusion By adding unlabelled EGF, it was possible to modify the cellular uptake of [¹²⁵I]trastuzumab. This points towards new approaches for the modification of radionuclide uptake in EGFR- and HER2-positive tumours.     

Granulocyte colony-stimulating factor affects serum levels of soluble interleukin-2 receptors after allogeneic stem cell transplantation

Soluble interleukin-2 receptor (sIL-2R) levels were analyzed in 127 stem-cell transplant recipients. Granulocyte-colony stimulating factor (G-CSF) was given to 57 patients after transplantation. We found an association between G-CSF and increased sIL-2R levels. This indicates increased T-cell activation and may be one reason for the previously found increased incidence of acute graft-versus-host disease in G-CSF-treated patients.     

Increased expression of chemokines in the skin of chronic proliferative dermatitis mutant mice

Chemokines direct the migration of leukocytes to sites of inflammation and are potential targets for anti-inflammatory therapy. Chronic proliferative dermatitis (cpdm/cpdm) mutant mice develop a persistent eosinophilic dermatitis associated with increased T(H)2 cytokines in the skin. Expression patterns of chemokines in the skin of cpdm/cpdm mice were evaluated to define the mechanisms driving cutaneous infiltration by leukocytes. RNA isolated from the skin of mutant and littermate control mice revealed a significant increase in Ccl1 (TCA-3), Ccl2 (MCP-1), Ccl11 (eotaxin), Ccl17 (TARC), Cxcl10 (IP-10), and the chemokine receptor Ccr3. The concentration of CCL11 protein was increased two- to threefold in the skin of cpdm/cpdm mice by enzyme-linked immunosorbent assay. In vitro culture of primary dermal fibroblasts from cpdm/cpdm and control mice with tumor necrosis factor, IL-4, and IL-13 stimulation did not reveal differences in their ability to secrete CCL11, suggesting that the increased chemokine expression observed in the skin of cpdm/cpdm mice is most likely caused by the increased T(H)2 cytokines in the dermis of this mouse model. Treatment of cpdm/cpdm mice with CCL11-neutralizing polyclonal antibodies did not affect the number of eosinophils in the skin or the severity of the dermatitis. Neutralizing multiple chemokines or chemokine receptors may be necessary to decrease eosinophil accumulation. The cpdm/cpdm mutant mouse is a potentially useful model to determine the role of various chemokines in eosinophil accumulation in chronic inflammation.     

Proteotypic classification of spontaneous and transgenic mammary neoplasms

Introduction  

Mammary tumors in mice are categorized by using morphologic and architectural criteria. Immunolabeling for terminal differentiation markers was compared among a variety of mouse mammary neoplasms because expression of terminal differentiation markers, and especially of keratins, provides important information on the origin of neoplastic cells and their degree of differentiation.     

Pharmacokinetic-pharmacodynamic interrelationships of intravenous and oral levosimendan in patients with severe congestive heart failure

OBJECTIVE: To assess the pharmacokinetic-pharmacodynamic (PK-PD) interrelations after a 6-hour continuous infusion and a 2 mg single oral dose of levosimendan in patients with congestive heart failure (CHF). METHODS: This was an open-label, non-randomized Phase II trial in 29 patients with New York Heart Association (NYHA) class III-IV CHF, comprising 2 study days. On the first day, patients were given 6-hour levosimendan infusion with the dose 0.2 microg/kg/min. After a 1-week washout, the patients received a 2 mg single oral dose of levosimendan. Heart rate-corrected electromechanical systole QS2i was the primary variable. Secondary variables were heart rate (HR), systolic (sBP) and diastolic blood pressure (dBP) and 24-hour ambulatory ECG (Holter). RESULTS: QS2i shortened from 515 ms at baseline to 506 ms at the end of 6-hour infusion (p = 0.007). After 2 mg single dose, QS2i shortened at 2 h after drug intake from 532 ms at baseline to 525 ms (p = 0.006). The effect was similar also at 8 h (532 ms vs 526 ms, p = 0.017). Mean of maximum shortening of QS2i observed during the infusion was 22 ms (p < 0.0001) and 17 ms after 2 mg single oral dose (p < 0.0001). The concentration-effect loops for QS2i showed a clear counter-clockwise hysteresis with both modes of administration. sBP and dBP decreased both during infusion and after 2 mg oral dose. HR remained unchanged during both modes of administration. CONCLUSIONS: Both 6-hour infusion and 2 mg single dose of levosimendan showed that levosimendan possesses moderate inotropic and vasodilatory effects in patients with severe congestive heart failure, which could be described as counter-clockwise hysteresis. It seemed that the vasodilatory effect appeared earlier than the inotropic effect.