Heterogeneity of B cell involvement in acute nonlymphocytic leukemia

In order to study the pattern of B cell involvement in acute nonlymphocytic leukemia (ANLL), multiple B lymphoid cell lines were established by Epstein-Barr virus transformation of peripheral blood mononuclear cells from two patients with the disease who were heterozygous for the X chromosome-linked glucose-6-phosphate dehydrogenase (G6PD). In one patient, the progenitor cells involved by the leukemia exhibited multipotent differentiative expression, whereas in the other patient the cells showed differentiative expression restricted to the granulocytic pathway. In the patient whose abnormal clone showed multipotent expression, the ratio of B-A G6PD in B lymphoid cell lines was skewed in the direction of type B (the enzyme characteristic of the leukemia clone) and significantly different from the 1:1 ratio expected. It is, therefore, likely that the neoplastic event occurred in a stem cell common to the lymphoid series as well as to the myeloid series. In contrast, evidence for B cell involvement was not detected in the patient whose ANLL progenitor cells exhibited restricted differentiative expression. These findings underscore the heterogeneity of ANLL. Clinically and morphologically similar malignancies in these two patients originated in progenitors with different patterns of stem cell differentiative expression. This difference may reflect differences in cause and pathogenesis.     

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.     

Intramedullary nailing versus external fixation in Gustilo type III open tibial shaft fractures: a meta-analysis of randomised controlled trials

Open tibial shaft fractures are the most common of long-bone open fractures. Management of the fracture is either by intramedullary nailing (IMN) or by external fixation (EF). Since the literature does not indicate clearly which is more effective, a meta-analysis was conducted to establish which approach is more suitable to treat Gustilo type III fractures. MEDLINE, the Cochrane Central Register of Controlled Trials, EMBASE and CINAHL databases were searched for randomised controlled trials (RCT) describing IMN and EF treatment of Gustilo type III fractures. As of 15 November 2012, five RCT involving 239 patients had been published; the outcomes examined in this study are their surgical complications. Data analysis led complications to be grouped into infection, fracture healing problems (non-union, malunion) and “other complications” (vascular injury, revision surgery, soft tissue damage, mechanical failure and tibial malalignment). IMN was associated with lower rates of infection and fracture healing problems; the differences between the two approaches for “other complications” were not significant. The data indicate that IMN is the treatment of choice for Gustilo type III fractures.     

Lumbar intraspinal mucous cyst: case report

We report a case of an intraspinal mucous cyst, or ganglionic cyst, that irritated the fifth nerve root on the left in a patient who had previously undergone L4-L5 discectomy due to lumbosciatica. After a few months of complete well-being, the patient complained of the return of sciantica in the L5 region. Clinically, it looked like the recurrence of disc hernia, however, tests showed the presence of an extradural ganglionic cyst adjacent to the left joint facet between lumbar vertebrae IV and V. This lesion was not seen using radiography or computed tomography prior to discectomy. Surgical excision of the lesion was followed by rapid and full remission of the clinical symptoms. Histological tests confirmed the diagnosis of ganglion cyst. Received: 23 August 2001/Accepted: 4 September 2001     

Hip fractures in Italy: 2000–2005 extension study

Summary

A total of 507,671 people ≥65 experienced hip fractures between 2000 and 2005. In 2005, 94,471 people ≥65 were hospitalized due to hip fractures, corresponding to a 28.5% increase over 6 years. Most fractures occurred in patients ≥75 (82.9%; n?=?420,890; +16% across 6 years), particularly in women (78.2%; n?=?396,967).

Introduction

We aimed to analyze incidence and costs of hip fractures in Italy over the last 6 years.

Methods

We analyzed the national hospitalization and DRG databases concerning fractures occurred in people ≥65 between 2000 and 2005.

Results

A total of 507,671 people ≥65 experienced hip fractures across 6 years, resulting in about 120,000 deaths. In year 2005 94,471 people aged ≥65 were hospitalized due to hip fractures, corresponding to a 28.5% increase over 6 years. The majority of hip fractures occurred in patients ≥75 (82.9%; n?=?420,890; +16% across 6 years) and particularly in women (78.2%; n?=?396,967). Among women, 84.2% of fractures (n?=?334,223; +28.0% over 6 years) were experienced by patients ≥75, which is known to be the age group with the highest prevalence of osteoporosis, accounting for 68.6% of the overall observed increase in the total number of fractures. Hip fractures in men ≥75 increased by 33.1% (up to 16,540). Hospitalization costs increased across the six examined years (+36.1%) reaching 467 million euros in 2005, while rehabilitation costs rose up to 531 million in the same year.

Conclusions

Hip fractures of the elderly are increasing and represent a major health problem in industrialized countries such as Italy.