Predictors of inotrope use during separation from cardiopulmonary bypass

OBJECTIVE: To identify the demographic, clinical, and echocardiographic features that predict the use of inotropic support at separation from cardiopulmonary bypass (CPB). Design: Retrospective study of consecutive patients undergoing coronary artery bypass graft (CABG) surgery. SETTING: Referral center for cardiothoracic surgery at a university hospital. PARTICIPANTS: One thousand nine patients undergoing either CABG or combined CABG and valve surgery with CPB in whom an intraoperative transesophageal echocardiography (TEE) examination was performed. INTERVENTIONS: Inotropic support was defined as the use of dopamine >/=5 microg/kg/min; any dose of epinephrine, norepinephrine, dobutamine, and milrinone; or the insertion of an IABP during separation from CPB. Support was implemented by the anesthesia care team as clinically indicated. Comprehensive TEE examinations were conducted before CPB in all patients according to published guidelines and subsequently reviewed by a single, independent operator. MEASUREMENTS and MAIN RESULTS: Inotropic support was used in a total of 394 patients (39%) at separation from CPB. The study identified 6 significant, independent predictors of inotrope use: (1) Wall Motion Score Index, (2) combined CABG and mitral valve repair or replacement surgery, (3) left ventricular ejection fraction <35%, (4) reoperation, (5) moderate-to-severe mitral regurgitation, and (6) aortic cross-clamp time. CONCLUSIONS: Incorporating data from a comprehensive intraoperative TEE examination, the authors identified 6 reproducible factors that independently predict the use of inotropic support at separation from CPB.     

Reversal of pancytopenia following kidney transplantation in a patient of primary hyperoxaluria with bone marrow involvement

Combined liver and kidney transplantation is the ideal treatment for patients with end-stage renal failure secondary to primary hyperoxaluria and systemic oxalosis, with a functioning liver providing replacement of the deficient enzyme and a functioning kidney providing the route of excretion for the oxalate crystals. Pancytopenia from bone marrow infiltration of oxalate crystals is a rare complication of primary hyperoxaluria, and its reversal following transplant has not been described. We report the first case of pancytopenia from marrow infiltration by oxalate crystals reversing following a successful kidney transplant alone. Although kidney alone transplants do not provide the best chance of survival or quality of life as compared to a combined kidney and liver transplant, a well functioning kidney transplant is able to take care of the systemic oxalate load and ameliorate, at least for a period of time, the systemic complications of oxalosis.     

Safety, tolerability, pharmacokinetics, and pharmacodynamics of an orally active novel camptothecin analog, DRF-1042, in refractory cancer patients in a phase I dose escalation study

The objective of this study was to characterize the maximum tolerated dose (MTD), dose-limiting toxicities (DLT), pharmacokinetics, and antitumor effects of DRF-1042, a novel camptothecin analog, in refractory solid tumor patients. DRF-1042 was given for 5 consecutive days for 2 weeks, repeated every 3 weeks at 1.5 to 270 mg/m(2). Adverse events were monitored following NCI-CTC. Pharmacokinetics of lactone and total forms were determined using validated high-performance liquid chromatography (HPLC) and noncompartmental methods. Efficacy was evaluated applying World Health Organization (WHO) criteria. The 1st course was used to determine DLT and MTD. Twenty-five patients received 73 courses of therapy. Myelosuppression and diarrhea were DLTs. MTD was 120 mg/m(2)/day. AUC increased approximately linearly with dose. The t(1/2) for lactone and total forms was 9.9 and 29 hours, respectively. AUCs correlated significantly with nadir leucopenia and grade 4 diarrhea. Two complete responses (CRs) and 2 partial responses (PRs) were observed. In addition, 4 stable diseases were observed. The recommended phase II dose is 80 mg/m(2)/day.     

Loss-adjusted survival of cervix cancer in Khon Kaen, Northeast Thailand

For incident cancers of the cervix uteri (601 cases) registered in the population-based cancer registry of Khon Kaen province, Northeast Thailand, in 1985-1990 loss-adjusted survival probabilities were estimated by a logistic regression model with four prognostic factors (age at diagnosis, stage of disease, place of residence and treatment), and compared with observed survival, estimated by the actuarial method. All patients were followed up for a minimum of 5 years, using both passive and active methods. In all, 27.6% of patients were lost to follow-up within 5 years of the index date. The overall observed survival at 5 years was 56.8% and loss-adjusted survival was 54.7%. The difference between the loss-adjusted and observed survival at 5 years was small: 2.1% overall, varying between 0.8 and 3.5 percent units for any prognostic group. The assumption of independence of loss to follow-up and death in the calculation of survival by the actuarial method in this, and probably in other, population-based series, is reasonable and leads to no material bias in the estimates.     

A laminar cortical model for 3D perception of slanted and curved surfaces and of 2D images: development, attention, and bistability

A model of laminar visual cortical dynamics proposes how 3D boundary and surface representations arise from viewing slanted and curved 3D objects and 2D images. The 3D boundary representations emerge from non-classical receptive field interactions within intracortical and intercortical feedback circuits. Such non-classical interactions within cortical areas V1 and V2 contextually disambiguate classical receptive field responses to ambiguous visual cues using cells that are sensitive to colinear contours, angles, and disparity gradients. Remarkably, these cell types can all be explained as variants of a unified perceptual grouping circuit whose most familiar example is a 2D colinear bipole cell. Model simulations show how this circuit can develop cell selectivity to colinear contours and angles, how slanted surfaces can activate 3D boundary representations that are sensitive to angles and disparity gradients, how 3D filling-in occurs across slanted surfaces, how a 2D Necker cube image can be represented in 3D, and how bistable 3D Necker cube percepts occur. The model also explains data about slant aftereffects and 3D neon color spreading. It shows how chemical transmitters that habituate, or depress, in an activity-dependent way can help to control development and also to trigger bistable 3D percepts and slant aftereffects. Attention can influence which of these percepts is perceived by propagating selectively along object boundaries.     

Basic concepts in the treatment of tuberculosis

Early diagnosis and prompt treatment of tuberculosis is important in order to minimize complications and sequelae. It is important to select the proper regimen and ensure that the patient is getting adequate number of drugs for adequate duration. The principles of short course chemotherapy and the rationale behind the currently recommended regimens are outlined in this article. Standard (daily or intermittent) 6-month short course regimens are sufficient to cure most forms of tuberculosis in children and only severe forms like miliary, meningitis and neuro-tuberculosis require a longer duration of treatment. Worldwide, the (directly observed therapy) DOTS strategy is now recommended in the order to ensure cure and cut down the transmission of disease in the community and wherever possible, should be employed in the treatment of tuberculosis in children also.     

An assessment of two different methods of left ventricular ejection time measurement by transesophageal echocardiography

Left ventricular ejection time (LVET) is an important component in evaluating left ventricular performance. This measurement is usually made by measuring the timing of the transaortic valve flow velocity by continuous-wave Doppler. Although M-mode has also been used for measuring LVET, it has not been compared with the Doppler method. We tested the hypothesis that the M-mode-measured duration of aortic valve opening is comparable to Doppler-derived measurement of LVET by transesophageal echocardiography (TEE). Measurements were made in 31 patients undergoing nonaortic valve cardiac surgery. The timing of transaortic flow by continuous-wave Doppler was compared with the M-mode-derived timing of aortic valve opening. There was close correlation (Pearson correlation coefficient, r = 0.86; P < 0.0001) between M-mode and Doppler measurements. There was no significant difference between the two techniques by linearity tests (P > 0.1). Bland-Altman analysis showed no significant bias. We confirmed the hypothesis that M-mode-derived measurement of LVET is comparable to Doppler-derived measurement of LVET. M-mode may be an acceptable alternative to the Doppler method, especially when transvalvular velocity gradients cannot be readily obtained. M-mode is a simple, yet often underused, method of evaluating LVET during TEE.     

Induction of CD8 T-cell-Ifn-gamma response and positive clinical outcome after immunization with gene-modified allogeneic tumor cells in advanced non-small-cell lung carcinoma

Large tumor burdens in advanced non-small-cell lung carcinoma (NSCLC) are thought to be immunosuppressive. To determine whether CD8-mediated immune responses could be elicited in stage IIIB/IV NSCLC patients, 14 subjects were immunized several times with allogeneic NSCLC cells transfected with CD80 (B7.1) and HLA-A1 or A2. Patients enrolled were matched or unmatched at the HLA A1 or A2 locus and their immune response compared. Immunization significantly increased the frequencies of interferon-gamma secreting CD8 T cells in all but one patient in response to ex vivo challenge with NSCLC cells. The CD8 response of matched and unmatched patients was not statistically different. NSCLC reactive CD8 cells did not react to K562. Clinically, five of 14 patients responded to immunization with stable disease or partial tumor regression. The study demonstrates that CD8 Ifn-gamma responses against nonimmunogenic or immunosuppressive tumors can be evoked by cellular vaccines even at advanced stages of disease. The positive clinical outcome suggests that nonimmunogenic tumors may be highly susceptible to immune effector cells generated by immunization.