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Biomedical subjects

R Kyle

Publications and source records attributed to R Kyle.

At least 19 recordsLinked to original sources
PubMed2006

International uniform response criteria for multiple myeloma.

New uniform response criteria are required to adequately assess clinical outcomes in myeloma. The European Group for Blood and Bone Marrow Transplant/International Bone Marrow Transplant Registry criteria have been expanded, clarified and updated to provide a new comprehensive evaluation system. Categories for stringent complete response and very good partial response are added. The serum free light-chain assay is included to allow evaluation of patients with oligo-secretory disease. Inconsistencies in prior criteria are clarified making confirmation of response and disease progression easier to perform. Emphasis is placed upon time to event and duration of response as critical end points. The requirements necessary to use overall survival duration as the ultimate end point are discussed. It is anticipated that the International Response Criteria for multiple myeloma will be widely used in future clinical trials of myeloma.

Humans↗
PubMed2001

Comparison of wire reinforced tubes with warmed standard tubes to facilitate fiberoptic intubation.

STUDY OBJECTIVE: To compare the ease of insertion of a warmed standard tracheal tube to that of a wire reinforced tracheal tube when placed over a flexible fiberoptic bronchoscope. DESIGN: Randomized controlled trial. SETTING: Tertiary care hospital. PATIENTS: 50 patients undergoing elective general anesthesia. INTERVENTIONS: Patients' tracheas were intubated with a flexible fiberoptic bronchoscope and had either a standard or wire-reinforced tracheal tube inserted. If resistance was met, the tube was withdrawn, rotated, and readvanced. This was repeated two times. If unsuccessful, the flexible fiberoptic bronchoscope was removed, and intubation was attempted with the other type of tracheal tube. MEASUREMENTS: The ability to advance the tracheal tube was determined. MAIN RESULTS: There were no demographic differences between the two groups. There was a similar ease of advancement of the two tracheal tubes. CONCLUSIONS: When performing elective flexible fiberoptic bronchoscopy for intubation, we recommend using the less expensive warmed standard tracheal tube.

Bronchoscopes↗
PubMed1999

Abnormal cytogenetics predict poor survival after high-dose therapy and autologous blood cell transplantation in multiple myeloma.

We compared the prognostic value of conventional cytogenetic analysis and established factors such as beta2-microglobulin and plasma cell labeling index in 70 patients undergoing autologous blood cell transplantation for multiple myeloma. Patients underwent transplantation 5 to 88 months (median, 20 months) after the initial diagnosis of myeloma. Factors studied were age, sex, beta2-microglobulin, response to prior therapy, plasma cell labeling index, cytogenetic analysis, bone marrow plasma cell percentage, lactate dehydrogenase and C-reactive protein. Twenty-eight of 65 patients (43%) had abnormal marrow cytogenetics. Overall survival measured from transplantation was significantly better in patients with normal cytogenetics than in those with abnormal cytogenetics (median survival, 25 vs 12 months, P = 0.003). Progression-free survival was better, with median times of 12 vs7 months, respectively (P = 0.005); overall survival measured from the time myeloma was first diagnosed was also longer, with median survivals of 62 and 39 months, respectively (P = 0.001). Median plasma cell labeling index was 1.5% in patients with abnormal cytogenetics and 0. 2% in those with normal cytogenetics (P < 0.001). Abnormal bone marrow cytogenetics predict poor survival after blood cell transplantation for myeloma. There is a significant correlation between abnormal cytogenetics and high plasma cell labeling index, suggesting that certain cytogenetic abnormalities may offer a proliferative advantage to myeloma cells.

Adult↗
PubMed1995

Sequential phenotyping of myeloma patients on chemotherapy: persistence of activated T-cells and natural killer cells.

To better detail the status of functional T cell subsets and natural killer cells in multiple myeloma, we undertook a detailed immunophenotypic study of circulating mononuclear cells in myeloma. We studied myeloma patients entered on a large prospective, randomized ECOG chemotherapy trial EST 9486 for patients with newly diagnosed multiple myeloma. All patients were studied prior to entry and then two months after initiation of therapy (e.g. post two cycles of Vincristine, BCNU, melphalan, cyclophosphamide and prednisone (VBMCP)). The chemotherapy protocol was a three-arm protocol utilizing either VBMCP, VBMCP alternating with interferon, or VBMCP with intermittent high dose cyclophosphamide. The major findings in this analysis include significant reductions in the white blood cell count, total lymphocytes, T cell (CD3+), T helper (CD4+), and T suppressor (CD8+) cells, after 2 cycles of VBMCP. However, there was a relative sparing of Natural killer (CD16+) and activated T cell (CD2+, HLADR+) reduction in these same patients. In summary, only two cycles of combination chemotherapy resulted in significant reductions in white blood cell and lymphocyte counts in multiple myeloma patients. All cell types appear to have been reduced by chemotherapy except for activated T cells and natural killer cells. The impact of selective modulation of functional T cells subsets during therapy for patients with multiple myeloma is an important parameter which needs to be addressed in the overall approach to these patients.

Flow Cytometry↗
PubMed1995

Exchange reamed intramedullary nailing for delayed union and nonunion of the tibia.

Twenty-eight tibial fractures, initially treated with nonreamed interlocking nails, were exchanged to reamed intramedullary nails to promote union. Initially, there were 8 closed fractures with compartment syndromes; 5 Type 2 open fractures; 6 Type 3 A injuries; and 6 Type 3B injuries. Exchange nailing was performed if followup radiographs did not show callus formation between 3 and 5 months after injury. Originally, 16 of the 28 nailings were statistically locked. Twenty-five of 27 fractures united after exchange nailing. In 2 patients with bone loss, additional bone grafting was required. Infection developed in 3 patients after exchange nailing (11%). Exchange nailing is a useful method to promote union of tibial fractures when slow consolidation occurs after initial treatment with a nonreamed nail. This method should be combined with autogenous bone grafting in patients with bone loss. The procedure is safe and effective in closed and minor open fractures; however, caution should be exercised in patients with prior Grade 3B open fractures because of the risk of infection.

Bone Nails↗
PubMed1993

Policy on welfare.

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Animal Welfare↗
PubMed1992

Detection and quantitation of malignant cells in the peripheral blood of multiple myeloma patients.

One of the distinguishing features of multiple myeloma (MM) is the proliferation of plasma cells that home to the bone marrow (BM). However, there still remains some uncertainty concerning the presence of related malignant cells in the peripheral blood of myeloma patients. Using consensus oligonucleotide primers, we amplified the third complementary determining region (CDR3) of rearranged immunoglobulin heavy chain alleles from MM marrow samples by polymerase chain reaction (PCR). From the sequences of the products, we derived allele-specific oligonucleotides (ASO), and these were used in subsequent amplification reactions to detect malignant clones in the peripheral blood of myeloma patients. This method is highly specific and sensitive to 1 malignant cell in the background of 10(5) normal cells. Using this method we detected circulating malignant cells in 13 of 14 previously untreated MM patients. Furthermore, by applying ASO-PCR to artificial titrations of initial BM DNA sample into normal peripheral blood lymphocyte (PBL) DNA we were able to generate standard curves and quantitate the amount of tumor in the patient PBL. We observed a wide variation in the amount of circulating tumor between patients. In addition, we found that the incidence of circulating tumor cells was independent of BM tumor burden and stage of disease. The detection and quantitation of circulating tumor cells in the PBL of MM patients may offer an alternative assessment of the disease and may be an important consideration in the use of peripheral stem cells in bone marrow transplantation.

Base Sequence↗
PubMed1991

Idiotypic cross-reactivity of immunoglobulins expressed in Waldenström's macroglobulinemia, chronic lymphocytic leukemia, and mantle zone lymphocytes of secondary B-cell follicles.

Monoclonal antibodies (MoAbs) specific for autoantibody-associated cross-reactive idiotypes (CRIs) of Waldenström's IgM react frequently with the surface Ig (slg) expressed by leukemia cells of patients with chronic lymphocytic leukemia (CLL). Evaluation of the molecular basis for this cross-reactivity indicates that such CRIs are encoded by conserved antibody variable region genes (V genes) that have undergone little or no somatic hypermutation. We find that such anti-CRI MoAbs stain a subpopulation of cells within the mantle zones surrounding the germinal centers of normal human tonsil. In contrast, MoAbs specific for variable region subgroup determinants react with cells in both the mantle zones and germinal centers of secondary B-cell follicles. To test whether mantle zone B cells not reactive with existing anti-CRI MoAbs may express slg bearing as-yet-unrecognized CRIs present on Igs produced by neoplastic cells of some patients with Waldenström's macroglobulinemia or CLL, we immunized mice with purified Waldenström's IgM that have been characterized for their variable region subgroups using subgroup-specific antisera raised against synthetic peptides. The supernatants of hybridomas generated from the splenocytes of immunized mice were screened for their ability to stain a subpopulation of mantle zone lymphocytes in human tonsil. With this approach, two new anti-CRI MoAbs were identified, designated OAK1 and VOH3. OAK1 binds to a CRI present on a subset of kappa light chains of the VK1 subgroup. VOH3 recognizes a CRI determinant(s) present on a subset of antibody heavy chains of the VH3 subgroup. Flow cytometric analyses demonstrated that OAK1 specifically binds leukemia cells from 5 to 20 patients (25%) with kappa light chain expressing CLL. In addition, VOH3 reacted with the leukemia cells from 1 of 17 (6%) patients tested. The success of these methods demonstrates that the variable regions of the Igs produced by mantle zone B cells share idiotypic determinants with Igs expressed in B-cell CLL (B-CLL) and Waldenström's macroglobulinemia.

Antibodies, Monoclonal↗
PubMed1990

The downward spiral of cattle veterinary practice.

Farm work for the cattle veterinary practitioner has declined in recent years, and further decline seems inevitable. With fewer dairy farms, and cattle farmers calling upon the veterinary surgeon less frequently, mixed practices are able to compensate by spending ever more time on small animal and horse work. But as cattle farmers know full well that younger veterinary surgeons are getting ever less experience with cattle, they are even less inclined to consult them. Here, I review the reasons for the downward spiral, and look for some solutions.

Animal Husbandry↗
PubMed1990

Medioventral medulla-induced locomotion.

Previous anatomical studies demonstrated the presence of descending projections from the physiologically identified mesencephalic locomotor region (MLR) to the medioventral medulla (MED) in the cat. The present experiments were designed to determine if a similar low threshold locomotion-inducing area is present in the rat medulla. In addition, the nature of the neurochemical control of this area of the brain was explored using localized injections of neurochemical agents in the decerebrate rat during locomotion on a treadmill. A region virtually identical to that reported in the cat was found to lead to controlled locomotion on a treadmill following stimulation at low amplitude currents (less than or equal to 60 microA). Injections of cholinergic agonists into the MED of the rat induced locomotion which could be blocked by injections of cholinergic antagonists. In addition, injections of GABA antagonists were found to induce stepping which could be blocked by injections of GABA or GABA agonists. Substance P (SP) also was found to induce walking following injection into the MED of the rat. Injections of an excitatory amino acid agonist (NMDA) also were found to induce locomotion in the rat. These effects were blocked by injections of an excitatory amino acid antagonist (APV). Since these results had not been reported for the cat MED, a short series of experiments revealed that the MED in the cat also responded to NMDA.

Animals↗
PubMed1989

Human IgM monoclonal proteins that bind 3-fucosyllactosamine, asialo-GM1, and GM1.

Analysis of monoclonal human Ig that occur in association with lymphoproliferative diseases has provided valuable information about antibody structure and idiotypes. We analyzed 940 human sera that contained monoclonal IgM proteins for their ability to bind to four carbohydrate epitopes. Ten sera bound asialo-GM1, five of these sera also bound GM1, 10 bound to 3-fucosyllactosamine (3-FL), and one each bound to levan and galactan. Although the antibody activity in each serum was associated with a single L chain isotype, both kappa and lambda isotypes were represented among the proteins that bound to asialo-GM1 and to 3-FL. Some antibodies against asialo-GM1 were highly specific for this compound, whereas others cross-reacted with the structurally related gangliosides GM1 and GD1b. The antibodies to asialo-GM1 also varied considerably in their ability to lyse liposomes that contain asialo GM1. An association of IgM mAb against gangliosides with peripheral neuropathies has been reported recently, but only one of five patients whose antibodies reacted with GM1 ganglioside had a neuropathy. The antibodies that bound 3-FL exhibited narrower specificity, and less than 10% cross reactivity was noted with structurally related carbohydrates. The frequency of monoclonal proteins that bound 3-FL and asialo-GM1, approximately 1:100 sera for each specificity, was surprisingly high in view of the fact that both of these epitopes are expressed in human tissues. We suggest that these antibodies may be poly-specific and/or that the subset of B lymphocytes that synthesizes these anti-carbohydrate antibodies undergoes malignant transformation more frequently than other B lymphocytes.

Antibodies, Monoclonal↗
PubMed1988

Bull fighting.

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Animal Welfare↗
PubMed1986

Monoclonal gammopathy and neuropathy: myelin-associated glycoprotein reactivity and clinical characteristics.

Immunoblot analysis was performed on the serum from 29 patients with polyneuropathy and monoclonal gammopathy. Nine patients had IgM spikes, and six of the nine had reactivity against myelin-associated glycoprotein (MAG) associated with a slowly progressive, predominantly sensory neuropathy. In contrast, 23 patients who lacked anti-MAG reactivity had more severe sensory motor neuropathy. Thus, IgM monoclonal gammopathy with reactivity against MAG may define a distinct clinical entity.

Adult↗
PubMed1981

The splanchnic autonomic outflow in amyloid neuropathy and Tangier disease.

The splanchnic outflow is important in the maintenance of postural normotension in humans. Pathology of outflow is usually associated with postural hypotension. Morphometric analyses were performed on the intermediolateral column neuron cell bodies at the T7 level in four cases of amyloid neuropathy and one case of Tangier disease. In amyloid neuropathy, postural hypotension is common; cell counts were reduced and ranged from 50 to 79% of control values. In Tangier disease, postural hypotension has not been reported; cell counts were normal.

Adult↗