A phase I/II study of decitabine in combination with panitumumab in patients with wild-type (wt) KRAS metastatic colorectal cancer.

PURPOSE: KRAS mutations are predictive of lack of response to monoclonal antibodies (mAb) against EGFR in metastatic colorectal cancer (mCRC). Most wild-type KRAS patients, however, are also resistant. Retrospective data suggest that EGFR silencing play a role in resistance to therapy. We conducted a study to evaluate the safety and efficacy of decitabine (a hypomethylating agent) in combination with panitumumab (mAb against EGFR) in mCRC patients. EXPERIMENTAL DESIGN: 20 patients with wild-type KRAS mCRC were included in this phase I/II study. Patients were treated with decitabine at 45 mg/m(2) IV over 2 h on day 1 and 15 and panitumumab 6 mg/kg IV over 1 h on day 8 and 22 every 28 days. Blood samples were collected at baseline, day 8, 15 and 22. Quantitative polymerase chain reaction was used to measure promoter-specific methylation in peripheral-blood cells (PBMCs). RESULTS: The most common adverse events were grade 1-2 (rash and hypomagnesemia); 3 (16 %) patients had grade III-IV neutropenia including one patient with neutropenic fever. Two of 20 patients (10 %) had a partial response. Both had previously received cetuximab. Ten patients had stable disease (3 of them longer than 16 weeks). Decreased methylation of the MAGE promoter was not evidenced in PBMCs. CONCLUSIONS: The combination of decitabine and panitumumab was well tolerated and showed activity in wild-type KRAS mCRC patients previously treated with cetuximab. Target modulation in surrogate tissues was not achieved and tumor biopsies were not available. Future studies evaluating hypomethylating agents in combination with EGFR mAb in patients with mCRC are warranted.

Neonatal alloimmune thrombocytopenia with significant HLA antibodies.

A case of neonatal alloimmune thrombocytopenia (NAIT) secondary to human platelet antigen (HPA)-1a antibodies is reported. Additional multispecific HLA antibodies rendered volunteer donor platelet transfusions ineffective. Despite a high incidence of maternal HLA antibodies in the pregnant population, there is only one previous report of clinically significant HLA antibodies.

Effect of structured preoperative teaching on anxiety levels of patients scheduled for cataract surgery.

Cataract surgery is an outpatient, fast-paced surgical intervention that requires preoperative patient education to ensure success. The purpose of this study was to determine the effect of structured preoperative instructions on anxiety levels of patients scheduled for cataract surgery. A pretest/posttest classical experimental design was used to test the hypothesis. Anxiety was assessed by using the Spielberger State-Trait Anxiety Inventory. Blood pressure, pulse, and respiration were measured to assess the stimulation of the sympathetic nervous system in response to stress. The findings of this study support the hypothesis that structured preoperative instructions will decrease the anxiety level of patients scheduled for cataract surgery.

A study: will waiting room time be reduced when the redesigned preliminary workup is performed by a certified ophthalmic technician?

The primary source of patient dissatisfaction in ophthalmic clinics is waiting room time. At one clinic, a study was conducted to determine whether redesignating preliminary workup tasks affected waiting room time. Previously, technicians and the ophthalmic registered nurse performed workups by taking histories, checking vision, reading glasses, performing refractions, conducting tonometry and slit lamp examinations, and dilating patients' eyes. Because the technicians' refractions were often inaccurate, the nurse or the doctor had to redo the refraction, prolonging waiting room times. Workup tasks, beginning with refractions, were transferred from the technicians to the nurse, which increased patient satisfaction and staff efficiency.

Identification of an HLA-A11 serological variant and its characterization by sequencing based typing.

We have identified an HLA-A11 variant allele, A*1105, segregating in a Caucasoid family. The variant antigen expressed by this allele failed to cross-react with most Caucasoid anti-HLA-A11 antisera tested. Sequencing based typing has been used to characterize this new allele and this showed that it has a novel mutation at a polymorphic position (502) in exon 3. In comparison with A*1101, the mutation (A-->G) results in an amino acid change from positively-charged lysine to negative glutamate and this may explain the altered HLA-A11 serological profile exhibited by this antigen. The new allele was found in a patient with acute lymphoid leukaemia (ALL), her father and two siblings.

Dynamic shimming for multi-slice magnetic resonance imaging.

Dynamic shimming has been implemented in three pulse sequences on a commercial GE Signa 1.5-T imaging system. Multi-slice field maps are acquired before the imaging sequence, and linear shim terms and center frequencies are calculated for each slice. During the imaging scan, the linear shim terms and center frequency are set before each pulse sequence repetition according to the current slice. Acquisition of multi-slice field maps and calculation of shim terms and center frequency for each slice are accomplished in a matter of seconds. Pulse sequences require only minimal modification to add dynamic shimming capability. Results are shown for a fat saturation spin-echo sequence, a single-shot echo-planar gradient-recalled echo sequence, and a spiral acquisition gradient-recalled echo sequence. In all cases, dynamic shimming with shim currents and center frequency optimized for each slice is shown to give better results than constant shim currents and a single center frequency optimized for the entire volume of interest.

Three-dimensional spectral-spatial excitation.

A method of three-dimensional spectral-spatial excitation is presented which is selective simultaneously in two spatial dimensions and in the spectral or chemical shift dimension. This method can be used to create spectral passbands whose center frequency varies as a function of spatial location within an imaging plane. This variation of passband center frequency may be specified by an acquired main field (B0) map; the resulting excitations compensate for inhomogeneity of the B0 field. In vivo images are presented in which three-dimensional spectral-spatial excitation allows selective water-only imaging in the presence of large B0 inhomogeneity where conventional spectrally selective imaging falls. Phantom studies give a detailed profile of the performance of three-dimensional spectral-spatial pulses suitable for water-only or fat-saturation imaging. These pulses may also be useful for fat and water suppression in spectroscopic imaging. Performance constraints imposed by limited gradient slew rates are analyzed and quantified.

Infantile osteopetrosis; bone marrow transplantation from a cousin donor.

The successful correction of infantile osteopetrosis in an Asian child by bone marrow transplantation (BMT) from an HLA-A,B matched cousin donor is reported. Retrospective HLA molecular analysis revealed that patient and donor were incompatible for HLA-DPB1. Donor type cells detected in the patient after transplantation indicate successful engraftment. The patient is currently alive and well.

Immunoradiometric assay for cytomegalovirus-specific IgG antibodies: assay development and evaluation in blood transfusion practice.

An immunoradiometric assay (radio-immunosorbent test; RIST) for the detection of IgG antibodies to human herpesvirus 4 [human cytomegalovirus (CMV)] has been developed. The technique utilizes CMV antigen passively adsorbed to a polyvinyl microtitration plate and a radiolabelled murine monoclonal anti-human IgG antibody to detect binding of human antibody to the 'solid phase' reagent. The assay was optimized, and its specificity confirmed by testing paired acute and convalescent sera from patients with acute CMV or other human herpesvirus infections. To determine the assay's sensitivity 1433 blood donor sera were examined. The RIST was more sensitive than a standard complement fixation (CFT), in that 53% of these sera were positive by RIST and 48% positive by CFT. There were 1303 concordant results, 88 sera positive only by RIST and 19 sera were only positive by CFT. These discrepant results remained after an attempt to exclude false positive reactivity; their significance is discussed. Use of a monoclonal anti-human IgG antibody in the RIST reduced non-specific binding to the control uninfected cell antigen such that blood donor sera could be tested in the assay using only a CMV antigen without generating an unacceptable false positive rate.

An HLA-DR negative acute leukaemia which stimulates MLC and CMC responses.

We describe an acute myelomonocytic leukaemia (E72) devoid of cell-surface HLA-DR antigens, but capable of inducing cellular responses. Leukaemia E72 induced proliferation of normal lymphocytes in primary mixed lymphocyte culture (MLC), which was only weakly inhibited by anti-DR sera. Depletion of a small percentage (congruent to 4%) of DR+ cells on a cell-sorter failed to abrogate the capacity of E72 to stimulate MLC and cell-mediated cytotoxicity (CMC) responses. We found that normal lymphocytes primed with E72 responded in secondary MLC to lymphocytes and leukaemias, suggesting that the lymphocyte-activating determinant (LAD) on E72 is not leukaemia-specific. In addition, E72 induced CMC responses to both leukaemias and lymphocytes. We suggest that E72 may express a novel HLA or non-HLA LAD.

Rapid micromethod for blood lead analysis by anodic stripping voltammetry.

We describe a rapid microscale procedure for blood lead determination by anodic stripping voltammetry. Results correlate well with those obtained by atomic absorption spectroscopy. The procedure involves use of a metal-exchange reagent, which rapidly releases bound lead from its macromolecular binding sites, thus eliminating a long and cumbersome perchloric acid digestion procedure. Reproducibility and analytical recovery of added lead were both excellent. Our results show that anodic stripping voltammetry is a reliable, sensitive micromethod for routine determination of blood lead.