Human acute leukemia cell line with the t(4;11) chromosomal rearrangement exhibits B lineage and monocytic characteristics

A cell line, designated RS4;11, was established from the bone marrow of a patient in relapse with an acute leukemia that was characterized by the t(4;11) chromosomal abnormality. The cell line and the patient's fresh leukemic cells both had the t(4;11)(q21;q23) and an isochromosome for the long arm of No. 7. Morphologically, all cells were lymphoid in appearance. Ultrastructurally and cytochemically, approximately 30% of the cells possessed myeloid features. The cells were strongly positive for terminal deoxynucleotidyl transferase. They were HLA-DR positive and expressed surface antigens characteristic for B lineage cells, including those detected by anti-B4, BA-1, BA-2, and PI153/3. Immunoglobulin gene analysis revealed rearrangements of the heavy chain and kappa chain genes. The cells lacked the common acute lymphoblastic leukemia antigen and antigenic markers characteristic of T lineage cells. The cells reacted with the myeloid antibody 1G10 but not with other myeloid monoclonal antibodies. Treatment with 12-O-tetradecanoyl- phorbol-13-acetate induced a monocyte-like phenotype demonstrated by cytochemical, functional, immunologic, and electron microscopic studies. The expression of markers of both early lymphoid and early myeloid cells represents an unusual phenotype and suggests that RS4;11 represents a cell with dual lineage capabilities. To our knowledge, RS4;11 is the first cell line established from t(4;11)-associated acute leukemia.     

Use of multiple T cell-directed intact ricin immunotoxins for autologous bone marrow transplantation

The monoclonal antibodies (MoAb) T101, G3.7, 35.1, and TA-1 were conjugated to intact ricin using a thioether linkage. These MoAb detect, respectively, the CD5[gp67], CD7[p41], CD2[p50], and [gp95, 170] determinants that are found in the vast majority of cases of T cell acute lymphocytic leukemia (T-ALL). The resulting immunotoxins (ITs) and an equimolar mixture of these ITs were evaluated as potential purgative reagents for autologous transplantation in T-ALL. Leukemic cell lines were used to compare the kinetics of protein synthesis inactivation mediated by each IT. The cells were treated with IT in the presence of lactose in order to block the native binding of ricin. The observed rates of protein synthesis inactivation correlated with target antigen expression detected by fluorescence-activated cell sorter analysis. Of the four ITs, T101-ricin (T101-R) exhibited the fastest rate of inactivation, followed in order by G3.7-ricin, TA-1-ricin, and 35.1-ricin. At concentrations greater than 300 ng/mL, a cocktail containing an equimolar amount of all four ITs (referred to as the four- IT cocktail) exhibited kinetics that were as fast or faster than those of T101-R. The long-term cytotoxic effects of individual ITs and the four-IT cocktail were evaluated using a sensitive clonogenic assay. Each IT was specifically cytotoxic and inhibited 1 to 4 logs of clonogenic leukemic cells at doses (300 to 600 ng/mL) that can be used clinically. The four-IT cocktail was highly cytotoxic; a concentration of 300 ng/mL inhibited greater than 4 logs of leukemic cells while sparing the majority of committed (CFU-GM, CFU-E) and pluripotent (CFU- GEMM) hematopoietic stem cells. The determination of both short-term kinetics of protein synthesis inactivation and longer-term inhibition of clonogenic growth allowed new insight into cell killing by IT. Our results suggest that ITs continue to act on clonogenic target cells for a period of three to five days. Interestingly, the four-IT cocktail was not as potent against clonogenic leukemic cells as T101-R alone, although it exhibited kinetics of protein synthesis inhibition that were as fast as those of T101-R alone. This finding suggests that internalized ITs may differ in the length of time they remain active within the cell. Our results also demonstrate the importance of using several different assays to evaluate IT reagents.     

Laparoscopic management of colorectal endometriosis

Background: In the past, intestinal endometriosis diagnosed at laparoscopy has generally required conversion to conventional surgery. The purpose of this study was to describe the laparoscopic management of colorectal endometriosis at a tertiary referral center. Methods: From November 1994 to March 1998, 509 consecutive patients with endometriosis requiring laparoscopic intervention were prospectively evaluated. Those with colorectal involvement were analyzed for stage of disease, procedure, operative time, conversion rate, length of hospitalization, and complications. Results: In 30 of the 509 patients (5.9%), colorectal involvement was identified. Twenty-eight of these 30 had stage IV disease. Intestinal involvement was suspected preoperatively in 13 of 30. Twelve required superficial excision of colon or rectal endometriomas. Protectomy/proctosigmoidectomy was done in seven cases, and rectal disc excision was performed in five patients. Four cases required conversion due to the overall severity of the pelvic disease. For those who did (n= 12) and did not (n= 18) require full-thickness excisions/resections, the median operative time was 180 min (range, 90–390) and 110 min (range, 45–355), respectively; the median length of hospitalization was 4 days (range, 3–7) and 1 day (range, 0–4), respectively. A major complication occurred in one patient (colovaginal fistula). At a median follow-up of 10 months (range 1–32), 28 patients were improved, and 24 of these had near or total resolution of preoperative symptoms. Conclusions: Extensive pelvic endometriosis generally requires rectal disc excision or bowel resection. In our experience, laparoscopic treatment of colorectal endometriosis, even in advanced stages, is safe, feasible, and effective in nearly all patients. Received: 1 April 1998/Accepted: 22 March 1999     

Sphenoidal sinus mucocele after transsphenoidal surgery for acromegaly

This report concerns one case of a sphenoid sinus mucocele occurring 17 years after transsphenoidal surgery for acromegaly. In 1979, a 51-year-old man was successfully operated by the transnasal transsphenoidal approach for a growth hormone (GH) adenoma 1 cm in diameter. In 1996, the patient was hospitalized for headaches and diplopia. He presented a loss of right visual acuity with paralysis of the right oculomotor nerve. The basal GH level was normal with a satisfactory decrease after oral glucose ingestion. Pituitary sellar radiography showed a disappearance of the posterior clinoid while magnetic resonance imaging revealed the existence of a bilocular, circular, homogeneous lesion of the sphenoid sinus 3 cm in diameter with a posterior and lateral extension. The diagnosis of mucocele was confirmed by surgical treatment, allowing drainage of the mucocele through a transsphenoidal approach. The drained material was composed of sinus epithelium containing many polynuclear and resorptive cells. Postoperatively, the symptoms decreased dramatically, leading to full recovery of visual function and disappearance of the headaches. Apart from the tumor recurrence, the mucocele of the sphenoid sinus can be evoked as a possible long term complication of transsphenoidal sugery for pituitary adenoma. Received: 2 June 1998 / Accepted: 23 February 1999     

Reduced variability of acetabular cup positioning with use of an imageless navigation system

Positioning the acetabular component is one of the most important steps in total hip arthroplasty; malpositioned components can result in dislocations, impingement, limited range of motion, and increased polyethylene wear. Conventional surgery makes use of specialized alignment guides provided by the manufacturers of the implants. The use of mechanical guides has been shown to result in large variations of cup inclination and version. We investigated acetabular cup alignment with the nonimage-based hip navigation system compared with a conventional mechanically guided procedure in 12 human cadavers. Postoperative cup position relative to the pelvic reference plane was assessed in both groups with the use of a three-dimensional digitizing arm. In the navigated group, a median inclination of 45.5 degrees and a median anteversion of 21.9 degrees (goals, 45 degrees and 20 degrees) were reached. In the control group, the median inclination was 41.8 degrees and the median anteversion was 24.6 degrees. The ninetieth percentile showed a much wider range for the control group (36.1 degrees-51.8 degrees inclination, 15 degrees-33.5 degrees anteversion) than for the navigated group (43.9 degrees-48.2 degrees inclination, 18.3 degrees-25.4 degrees anteversion). This cadaver study shows that computer-assisted cup positioning using a nonimage-based hip navigation system allowed for more consistent placement of the acetabular component.     

Navigation improves accuracy of rotational alignment in total knee arthroplasty

Successful total knee arthroplasty is dependent on the correct alignment of implanted prostheses. Major clinical problems can be related to poor femoral component positioning, including sagittal plane and rotational malalignment. A prospective randomized study was designed to test whether an optical navigation system for total knee arthroplasty achieved greater implantation precision than a nonnavigated technique. The primary variable was rotation of the femoral component in the transverse plane, measured from postoperative radiographs and computed tomography images. Sixty-four patients were included in the study. All patients received the Duracon total knee prosthesis. The patients were randomly divided into two groups: Group C patients had conventional total knee arthroplasty without navigation; Group N patients had total knee arthroplasty using a computer-assisted knee navigation system. Analysis showed that patients in Group N had significantly better rotational alignment and flexion angle of the femoral component than patients in Group C. In addition, superior postoperative alignment of the mechanical axis, posterior tibial slope, and rotational alignment was achieved for patients in Group N. The use of a navigation system provides improved alignment accuracy, and can help to avoid femoral malrotation and errors in axial alignment.     

Pharmacokinetics of remifentanil and its major metabolite, remifentanil acid, in ICU patients with renal impairment

Background. The pharmacokinetics of remifentanil, an opioidanalgesic metabolized by non-specific esterases, and its principalmetabolite, remifentanil acid (RA), which is excreted via thekidneys, were assessed as part of an open-label safety studyin intensive care unit (ICU) patients with varying degrees ofrenal impairment. Methods. Forty adult ICU patients with normal/mildly impairedrenal function (creatinine clearance [CL_cr] 62.9 (SD) 14.5 mlmin^–1; n=10) or moderate/severe renal impairment (CL_cr14.7 (15.7) ml min^–1; n=30) were included. Remifentanilwas infused for up to 72 h, at a starting rate of 6–9µg kg^–1 h^–1 titrated to achieve a target sedationlevel, with additional propofol (0.5 mg kg^–1 h^–1)if required. Intensive arterial sampling was performed for upto 72 h after infusion. Pharmacokinetic parameters obtainedby simultaneous modelling of remifentanil and RA data were statisticallycompared between the two groups. Results. Remifentanil pharmacokinetics were not significantlyaffected by renal status. RA clearance in the moderate/severegroup was reduced to about 25% that of the normal/mild group(41 (29) vs 176 (49) ml kg^–1 h^–1, P<0.0001).Metabolic ratio, a predictor of the ratio of RA to remifentanilconcentrations at steady state, was approximately eight-foldhigher in the moderate/severe group relative to the normal/mildgroup (116 (110) vs 15 (4), P<0.0001). Maximum RA levelsapproached 700 ng ml^–1 in the moderate/severe group. Conclusions. Although RA accumulates in patients with moderate/severerenal impairment, pharmacokinetic modelling predicts that RAconcentrations during a 9 µg kg^–1 h^–1 remifentanilinfusion for up to 15 days would not exceed those reported inthe present study, for which no associated prolongation of µ-opioideffects was observed. Br J Anaesth 2004; 92: 493–503     

Orthopaedic-induced anemia: the fallacy of autologous donation programs

Total knee arthroplasty is associated with significant blood loss. Despite the initiation of various blood conservation modalities, allogeneic transfusion has yet to be eliminated. One hundred forty-eight patients who had unilateral primary total knee arthroplasties during a 3-year period were evaluated retrospectively for blood loss and transfusion rates. The patients were prescribed one unit of preoperative autologous donation that was to be transfused automatically on postoperative Day 1. Allogeneic transfusion was based on symptoms, and no numerical transfusion triggers were used. The preoperative autologous donation program resulted in increased preoperative anemia. Whereas only 26.2% of patients were in the high transfusion-risk group (hemoglobin >10 g/dL and < or = 13 g/dL) before surgery, 55.7% of patients were in this high-risk category after preoperative autologous donation. The patients did not recover from the autologous donations that occurred 4 weeks before surgery. A mean hemoglobin level of 14.0 g/dL was seen before donation, whereas the mean preoperative hemoglobin level decreased to 12.6 g/dL. We think that a preoperative autologous donation program leads to an increased risk of anemia before surgery.