Simultaneous split-thickness skin grafting and placement of endosteal implants in the edentulous mandible: a preliminary report.

Reconstruction of the edentulous atrophic mandible continues to be a treatment problem for the oral and maxillofacial surgeon. Clearly, endosteal osseointegrated implants are indicated for rehabilitation, but a total implant-supported prosthesis may not always be possible. The implant-supported overdenture is an excellent alternative, but modifications of the unfavorable residual ridge may be necessary. Attached crestal soft tissue, resistant to mechanical trauma, and improvement of the residual ridge anatomy are provided by adding a split-thickness skin graft vestibuloplasty (VSG) and lowering of the floor of the mouth (LFM). Simultaneous VSG and LFM with placement of endosteal implants provides the optimal condition for maximal rehabilitation of the atrophic mandible with specific indications. Results of four skin grafts and eight implants simultaneously placed are reported.

The indirect estimation of hemoglobin concentration in whole blood.

The present conventional methods for determination of Hemoglobin (Hb) concentration in whole blood depend on the direct colorimetric measurement of chemically modified Hb following its release from red cells by lysis. This paper examines an alternative, indirect method which does not require initial red cell lysis, corrects for the falsely elevated Hb due to the lipemic plasma and determines whether elevated WBC count effects a change in the Hb value, without the tedious laboratory manipulations currently required to correct for these artifacts. The method is simple, uncomplicated and is based on the observation of a constant ratio (2.98) between the Mean Corpuscular Volume (MCV) and the Mean Corpuscular Hemoglobin (MCH) indices obtained from standard electronic counters in use in most laboratories. The Hb concentration is calculated by the equation: [formula: see text]. The resultant Hb measurements show an acceptable degree of accuracy and precision when compared with the direct measurements obtained from a Coulter Model S + I, even in the presence of a high WBC or lipid.

Hb A2-Parkville or delta 47(CD6)Asp----Val, a new delta chain variant.

A new delta chain variant, Hb A2-Parkville [delta 47(CD6)Asp----Val], has been identified in a female of Italian parentage. The mobility of the variant is less than carbonic anhydrase towards the anode at alkaline pH.

Spontaneous complete remission of chronic myeloid leukaemia following haematological relapse after allogeneic bone marrow transplantation.

A 31-year-old woman with Philadelphia (Ph) chromosome-positive chronic myeloid leukaemia (CML) underwent allogenic bone marrow transplantation during accelerated phase. Non-T-cell-depleted marrow from a male sibling mismatched at one Class 2 histocompatibility locus was infused after conditioning with total body irradiation and intravenous cyclophosphamide. Cyclosporin and methotrexate were given for prevention of graft-versus-host disease (GVHD). Prompt engraftment occurred with donor karyotype cells, followed by transient moderate acute GVHD. However, by day 60 after BMT, haematological relapse occurred with increasing splenomegaly, leucocytosis, increasing marrow fibrosis, and cytogenetic mosaicism, consisting of 47% donor metaphases with 53% Ph-positive host metaphases, some containing additional structural changes. Thirty days later further cytogenetic progression was evident. A slowly progressive fungal pneumonia concurrently present was treated with intravenous amphotericin and gradual reduction of cyclosporin. Subsequently, without further cytotoxic chemotherapy, pancytopenia and bone marrow hypoplasia developed, and on day 144 only donor karyotype marrow cells were seen. Chromosomes have remained of donor type on subsequent occasions, and the patient has a normal performance status 25 months after BMT. The patient's course illustrates that factors operating after allogeneic BMT contribute to longterm control of CML. The factors potentially responsible for this spontaneous remission, after early relapse, are discussed.

Autologous bone marrow transplantation for acute myeloid leukaemia in remission: a preliminary report.

Autologous bone marrow transplantation, using unpurged cryopreserved autologous marrow, was performed on ten adult patients with acute myeloid leukaemia in remission. Seven patients were in first chemotherapy-induced remission of their disease, while three were in later remission. Patients ages ranged from 24 to 52 years, with a median of 38.5 years. Conditioning therapy consisted of oral busulphan 16 mg/kg over four days and intravenous cyclophosphamide 60 mg/kg on two days. Bone marrow cells were thawed and infused two days later. All patients showed signs of marrow engraftment, however this was delayed in comparison with patients receiving allogeneic transplants. All patients developed fever requiring antibiotic therapy and one patient died of overwhelming sepsis. Another patient died of hepatic veno-occlusive disease two months after transplant. Serious, but non-fatal, hepatic complications occurred in two other patients. One patient, transplanted in third remission, relapsed 16 months post-autograft. No other relapses have been seen, with one second remission patient remaining leukaemia-free at 24 months, and six first remission patients in continuing remission 11 to 23 (median 20) months post transplant. These encouraging results require confirmation in a randomised clinical trial comparing autologous marrow transplantation versus standard chemotherapy.

Lack of correlation between immunoglobulin and T cell receptor gene rearrangements and TdT expression in acute myeloid leukaemia.

Thirty-two cases of acute myeloid leukaemia (AML) were examined for expression of terminal deoxynucleotidyl transferase (TdT) and rearrangements of the genes coding for the immunoglobulin heavy chain and the beta chain of the T cell receptor, in order to establish whether these two forms of lineage infidelity are linked. In 17 cases of AML with greater than or equal to 10% TdT+ cells, three cases showed evidence of gene rearrangement, two having clonal rearrangements in the immunoglobulin gene and one with a rearranged T cell receptor gene. Among 15 AML cases without significant numbers of TdT-positive blasts, three cases had rearrangements in both immunoglobulin and T cell receptor genes, while a fourth case had an immunoglobulin gene rearrangement. No relationship was seen between lymphoid gene rearrangements and expression of the lymphoid surface antigens CD7 and CD10. The lack of association between TdT expression and gene rearrangements does not support the concept of an orderly activation of the recombinase machinery in those cases of AML with features of early lymphoid differentiation.

Unusual immunophenotypes in acute leukaemias: incidence and clinical correlations.

The incidence and clinical implications of unusual patterns of expression of leucocyte differentiation antigens in acute leukaemia were assessed on 568 newly diagnosed paediatric and adult cases undergoing immunophenotyping with a panel of monoclonal antibodies at a single centre. Among patients with the precursor B (common) form of acute lymphoblastic leukaemia (ALL), the major variant seen was the group of 15 cases with expression of myeloid surface antigens. 4.5% of ALL cases tested with antibody to CD-11b were positive, 5.1% were CD-13+, and 10.8% CD-33+. All 15 patients achieved a complete remission with chemotherapy, with six of eight children and four of seven adults remaining disease free. A smaller proportion (1.5%) of precursor B ALL patients showed expression of the T lineage marker, CD-7. The only significant variant seen in the precursor T-ALL group was expression of HLA-DR antigen, which was found in five of 35 cases; although all responded to treatment, only one remains a disease-free survivor. Among patients with acute myeloid leukaemia (AML), expression of the lymphoid markers terminal transferase (TdT) and CD-7 were commonly seen (22.2% and 28.4% respectively of cases tested). Other lymphoid markers detected on AML cases were CD2 (11.1%), CD-10 (1%) and CD-19 (4.4%). These results confirm that examples of lineage infidelity are regularly seen in large series of patients with acute leukaemia. Prospective studies using uniform treatment protocols are required to establish whether these patients have significantly different disease outcomes.

Hemoglobin Windsor or beta 11 (A8)Val----Asp: a new unstable beta-chain hemoglobin variant producing a hemolytic anemia.

A new beta-chain variant, Hemoglobin Windsor [beta 11 (A8)Val----Asp] was discovered in a 9-month-old child who presented with a hemolytic anemia of 59 g/l with an intercurrent viral infection. Her blood film demonstrated fragmented cells, target cells, stipple cells, nucleated red cells, polychromasia and some spherocytes, indicative of acute hemolysis. Hemoglobin electrophoretic studies were requested and a beta-chain variant, constituting 27% of the total hemoglobin, separated towards the anode under alkaline conditions. The variant was unstable, producing numerous "Hb H"-like inclusions and a positive isopropanol stability test. The variant hemoglobin was purified by precipitation. The variant beta-chain was purified by column chromatography and its tryptic peptides fractionated by high performance liquid chromatography. Amino acid analysis and sequence data indicated that the valine at position 11(A8) had been substituted by an aspartic acid residue. This substitution, in the bottom of the heme pocket, has resulted in instability of the hemoglobin molecule and an increase in oxygen affinity. The variant appears to have resulted from a spontaneous mutation as both parents are hematologically normal. A younger sibling is also hematologically normal.

Hemoglobin Randwick or beta 15 (A12)Trp----Gly: a new unstable beta-chain hemoglobin variant.

A new beta-chain hemoglobin variant, Hb Randwick [beta 15(A12)Trp----Gly] was detected in a 43-year-old female of Northern Italian parentage. During investigation for possible diabetes, mild red cell changes were noted and hemoglobin electrophoresis studies were requested. Independently, her sister's assessment had resulted in similar investigations. The most prominent findings were numerous "Hb H"-like inclusions and a positive isopropanol stability test. The hemoglobin variant separated poorly towards the anode at pH 9.2 and the level was estimated to be between 48-50% of the total hemoglobin. The variant beta-chain was partially purified by column chromatography, and its tryptic peptides fractionated by high performance liquid chromatography. Amino acid analysis and sequence data indicated that the tryptophan at residue 15 (A12) had been substituted by a glycine residue. Further study has indicated that eight other family members are heterozygous for the variant; they are clinically normal with no evidence of splenomegaly or history of jaundice, although four of them showed a mild reticulocytosis.

Hemoglobin Hobart or alpha 20(Bl)His----Arg: a new alpha chain hemoglobin variant.

A new alpha chain hemoglobin variant, Hb Hobart, alpha 20(Bl)His----Arg, was detected in a 60-year-old female of British nationality. The proposita had a history of severe rheumatoid arthritis and had been treated for many years for a refractory microcytic anemia and/or iron deficiency. A hemoglobin electrophoresis screen indicated the presence of a hemoglobin variant, with electrophoretic characteristics similar to a Hb Lepore. However, the level of the variant (17.9%) and the presence of a minor variant Hb A2 band (0.4%) suggested that further investigation was indicated. The variant hemoglobin was purified by column chromatography and the alpha chain subjected to aminoethylation and tryptic digestion. Peptide mapping and amino acid analysis indicated that the histidine residue 20 had been substituted by an arginine residue. The substitution in Hb Hobart is at the first residue in the B Helix of the alpha chain of hemoglobin. As this is an externally placed amino acid in the hemoglobin molecule, a substitution at this position of the hemoglobin molecule would not be expected to cause any functional problems. A family study has shown that at least three other relatives are heterozygous for Hb Hobart. These family members have normal hematological findings.

Should calcium be used in cardiac arrest?

Calcium salts have been recommended for and used in the treatment of various forms of cardiac arrest for many years. Although calcium plays a major role in excitation-contraction coupling, it can have a deleterious effect in some processes of cellular injury. Clinical trials suggest that calcium salts are not effective in ventricular fibrillation and asystole, but that some patients with electromechanical dissociation may have a favorable hemodynamic response. Because of the potential risks of calcium salts, their use should be limited to specific subsets of patients with cardiac arrest.

Monoclonal antibody analysis of canine hemopoietic cells. Role of Ia-like and Thy-1 antigens in bone marrow engraftment.

The expression of Ia-like (class II MHC) antigens on canine hemopoietic cells was investigated using a cytotoxic murine monoclonal antibody, WM-2, reactive with dog Ia-like antigens. Another monoclonal antibody, WMD-1, reactive with canine Thy-1 antigen, was used as a positive control. Depletion of Ia+ cells from dog bone marrow by complement-mediated lysis with WM-2 antibody failed to inhibit growth of granulocyte-macrophage progenitors (CFUGM) in vitro, while WMD-1 produced complete inhibition of CFUGM. Lethally irradiated dogs receiving bone marrow autografts depleted of Ia-positive cells ex vivo showed initial engraftment, followed by prolonged pancytopenia, and eventual complete recovery of marrow function in the majority of animals. In contrast, dogs receiving autografts treated with WMD-1 and complement all died of marrow failure. We interpret these results as indicating: (1) that Thy-1 antigen is present on hemopoietic stem cells essential for marrow engraftment; and (2) that the expression of Ia antigens on hemopoietic cells is heterogeneous and related to the level of stem cell maturation. While Ia appears to be present on a stem cell population at an earlier stage than CFUGM, as evidenced by the transient phase of graft failure seen in dogs receiving Ia-depleted marrow, the most primitive stem cell, responsible for long-term engraftment, is effectively Ia-negative.

Standardization of monoclonal antibodies for use in autologous bone marrow transplantation for common acute lymphoblastic leukemia.

Two monoclonal antibodies suitable for leukemia cell purging of remission bone marrow from patients with common acute lymphoblastic leukemia (common-ALL) are described. WM-21, reacting with the gp 100 common-ALL associated antigen (CALLA), and FMC-8, reactive with a p24 surface antigen, both bind to the majority of leukemic blast cells from cases of common ALL, and promote complement-mediated lysis of CALLA+ leukemias and cell lines. After initial dye exclusion studies to standardize antibody and rabbit complement concentrations and incubation times, an in vitro plating assay using CALLA+ p24+ cell lines was used to investigate the lytic ability of monoclonal antibody treatment. Incubation with WM-21, FMC-8, and complement produced up to 5 logs inhibition of growth in this system. Under similar conditions, no inhibition of in vitro growth of normal bone marrow myeloid progenitor cells was seen. These antibodies therefore appear to be useful therapeutic reagents for removing residual common ALL blast cells from bone marrow prior to autologous marrow transplantation.

Myeloid progenitor surface antigen identified by monoclonal antibody.

A mouse monoclonal antibody, WM-15, has been developed which reacts with a human myeloid lineage-restricted cell surface antigen. WM-15, an IgG1 antibody, reacts with a mean of 3.8% of normal bone marrow mononuclear cells, identifying predominantly promyelocytes and myeloblasts, and in fluorescence-activated cell sorting experiments produces enrichment of bone marrow granulocyte-macrophage progenitor cells. Normal mature monocytes and granulocytes are weakly labelled by WM-15, but other haemopoietic cells including erythroblasts and all lymphoid cells are unreactive. The myeloid specificity of this antibody is highlighted by its reactivity with myeloid leukaemia cell lines and 65% of cases of acute myeloid leukaemia, while lymphoid cell lines and leukaemias are WM-15 negative. WM-15 appears to be a useful reagent for further investigation of normal and abnormal myelopoiesis.

Human myeloid differentiation antigens identified by monoclonal antibodies: expression on leukemic cells.

Six murine monoclonal antibodies reactive with human myeloid lineage differentiation antigens are described. These antibodies, designated WM-12, WM-14, WM-15, WM-16, WM-19, and WM-20, react with normal peripheral blood neutrophils and monocytes, as well as a proportion of myeloid precursor cells in bone marrow, but fail to react with the majority of normal lymphoid cells. Immunoprecipitation studies have demonstrated binding of WM-12, -14, -16, -19, and -20, to elements of a protein multimer with sub-units of 50, 105, and 170 kilodalton molecular weight under reducing conditions. WM-15 antibody, however, reacts with a separate protein of 165 kilodaltons. These 6 antibodies reacted with 89% of cases of acute myeloid leukemia, but showed significant binding with only occasional cases of acute lymphoblastic leukemia. Cases of AML (FAB M1 and M2) were more frequently positive with WM-15 (60% of cases positive) than with the other 5 antibodies, whereas the converse was true for leukemias with monocytic differentiation (FAB M4 and M5; 82-100% of cases positive with WM-12, -14, -16, -19, -20). These antibodies appear useful for diagnosis and classification of acute leukemia.