Correction to: Acute respiratory failure and the kinetics of neutrophil recovery in pediatric hematopoietic cell transplantation: a multicenter study.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Acute respiratory failure and the kinetics of neutrophil recovery in pediatric hematopoietic cell transplantation: a multicenter study.

In this multicenter study, we investigated the kinetics of neutrophil recovery in relation to acuity and survival among 125 children undergoing allogeneic hematopoietic cell transplantation (allo-HCT) who required invasive mechanical ventilation (IMV). Recovery of neutrophils, whether prior to or after initiation of IMV, was associated with a significantly decreased risk of death relative to never achieving neutrophil recovery. A transient increase in acuity (by oxygenation index and vasopressor requirements) occurred among a subset of the patients who achieved neutrophil recovery after initiation of IMV; 61.5% of these patients survived to discharge from the intensive care unit (ICU). Improved survival among patients who subsequently achieved neutrophil recovery on IMV was not limited to those with peri-engraftment respiratory distress syndrome. The presence of a respiratory pathogen did not affect the risk of death while on IMV but was associated with an increased length of IMV (p < 0.01). Among patients undergoing HCT who develop respiratory failure and require advanced therapeutic support, neutrophil recovery at time of IMV and/or presence of a respiratory pathogen should not be used as determining factors when counseling families about survival.

A randomized phase I trial of chronic oral etoposide with or without granulocyte-macrophage colony-stimulating factor in patients with advanced malignancies.

Data from an in vitro human tumor-cloning assay suggested synergistic cytotoxicity when etoposide (VP16) and granulocyte-macrophage colony-stimulating factor (GM-CSF) were combined. To explore this potential, we undertook a prospectively randomized three-arm trial in a phase I setting with various schedules of VP16 and GM-CSF. Thirty-one patients were enrolled in the three-arm trial. Arm A consisted of oral VP16 daily for up to 21 days with cycles repeated every 35 days. Arm B included oral VP16 daily for up to 21 days plus concomitant GM-CSF at 5 micrograms/kg/day s.c. days 1-10. Arm C included oral VP16 daily for up to 21 days plus pretreatment with GM-CSF at the same dose for 5 days (days -6 to -2). VP16 was begun at 25 mg/m2/day on level 1 and increased to 50 mg/m2/day on level 2. Twenty-seven patients were evaluable for toxicity, nine on each arm (six patients on each arm on level 1, three patients on each arm on level 2). Neutropenia on arm B (concomitant VP16 and GM-CSF) was earlier and more profound than on arm A or C. The median absolute neutrophil count and day of nadir for arms A, B, and C were 3295, 988, and 1600/mm3 and days 23, 15, and 26, respectively. Thrombocytopenia was generally uncommon except on arm C level 2, where the median platelet count was 26,000/mm3. One partial response (arm B) in a patient with non-small cell lung cancer was seen. Dose intensity favored arm A. Neither concomitant therapy with VP16 and GM-CSF (arm B) nor pretreatment with GM-CSF (arm C) improved dose intensity over VP16 alone (arm A), and arms B and C were complicated by increased neutropenia and thrombocytopenia.

Phase I and pharmacokinetic trial of weekly CPT-11.

PURPOSE: We conducted a phase I and pharmacokinetic trial of CPT-11 (irinotecan) to characterize the maximum-tolerated dose (MTD), toxicities, pharmacokinetic profile, and antitumor effects in patients with refractory solid malignancies. PATIENTS AND METHODS: We treated 32 patients with CPT-11 administered as a 90-minute intravenous infusion every week for 4 consecutive weeks followed by a 2-week rest period. Dose levels ranged from 50 to 180 mg/m2/wk. We determined concentrations of the lactone (active) and total (lactone plus carboxylate) forms of CPT-11 and its metabolite, SN-38, in the plasma and urine of selected patients during and after drug infusion. RESULTS: Grade 4 diarrhea was the dose-limiting toxicity (DLT) at the 180-mg/m2/wk dose level. Other toxicities attributed to CPT-11 included dehydration, nausea, vomiting, and asthenia. Hematologic toxicity was mild in most patients. The terminal plasma half-life for CPT-11 (total) was 7.9 +/- 2.8 hours, for CPT-11 (lactone) 6.3 +/- 2.2 hours, for SN-38 (total) 13.0 +/- 5.8 hours, and for SN-38 (lactone) 11.5 +/- 3.8 hours. We observed significant correlations between drug dose and peak plasma concentration (Cpmax) and between drug dose and area under the concentration curve (AUC) for CPT-11, but not for SN-38. CONCLUSION: The MTD for CPT-11 in this patient population was 150 mg/m2/wk when administered on a weekly-times-four schedule repeated every 6 weeks. At dose levels greater than 150 mg/m2/wk, diarrhea is dose-limiting.

Phase II trial of irinotecan in patients with progressive or rapidly recurrent colorectal cancer.

PURPOSE: To evaluate irinotecan (CPT-11; Yakult Honsha, Tokyo, Japan) in patients with metastatic colorectal carcinoma that had recurred or progressed following fluorouracil (5-FU)-based therapy. PATIENTS AND METHODS: Patients were treated with irinotecan 125 to 150 mg/m2 intravenously (IV) every week for 4 weeks, followed by a 2-week rest. Forty-eight patients were entered onto the study and all were assessable for toxicity. Forty-three patients completed one full course of therapy and were assessable for response. RESULTS: One complete and nine partial responses were observed (response rate, 23%; 95% confidence interval [CI], 10% to 36%). The median response duration was 6 months (range, 2 to 13). The median survival time was 10.4 months and the 1-year survival rate was 46% (95% CI, 39% to 53%). Grade 4 diarrhea occurred in four of the first nine patients (44%) treated on this study at the 150-mg/m2 dose level. The study was amended to reduce the starting dose of irinotecan to 125 mg/m2. At this dose, nine of 39 patients (23%) developed grade 4 diarrhea. Aggressive administration of loperamide also reduced the incidence of grade 4 diarrhea. Grade 4 neutropenia occurred in eight of 48 patients (17%), but was associated with bacteremia and sepsis in only case. CONCLUSION: Irinotecan has significant single-agent activity against colorectal cancer that has progressed during or shortly after treatment with 5-FU-based chemotherapy. The incidence of severe diarrhea is reduced by using a starting dose of irinotecan 125 mg/m2 and by initiating loperamide at the earliest signs of diarrhea. These results warrant further clinical evaluation to define the role of irinotecan in the treatment of individuals with colorectal cancer.

Usefulness of transesophageal imaging of flow convergence region in the operating room for evaluating isolated patent ductus arteriosus.

Transesophageal echocardiography (TEE) was performed in 21 patients with isolated patent ductus arteriosus (PDA) with a color Doppler flow convergence method during surgical closure of the ductus. Evaluation of PDA by TEE with the flow convergence method may provide valuable information during surgery and/or thorascopic ductus clipping.

Micromultiplane transesophageal echocardiographic probe for intraoperative study of congenital heart disease repair in neonates, infants, children, and adults.

This study reports the development of a micromultiplane 8.2-mm transesophageal echocardiographic probe. The probe is applicable to newborn infants and can deliver diagnostic images in adults.

Rounded atelectasis due to acute exudative effusion. Spontaneous resolution.

Rounded atelectasis is an interesting roentgenographic entity that must be distinguished from intrathoracic neoplasm. Chronic pleural disease, particularly that due to asbestos exposure, is a frequently cited cause, and is considered to be a sine qua non by some. We report a case of rounded atelectasis with an acute parapneumonic exudative effusion that resolved spontaneously with roentgenographically normal pleura.

Comparison of forceps used for transbronchial lung biopsy. Bigger may not be better.

Transbronchial lung biopsy is a useful procedure to obtain an alveolar specimen in the evaluation of diffuse lung infiltrates. Large forceps (cup and alligator) are expected to result in larger specimens and improve diagnostic yield. We performed transbronchial lung biopsy in 20 patients using two different sized forceps in each patient. We compared the histology and histopathologic diagnoses obtained by small cup forceps, large cup forceps, and large alligator forceps. Small and large cup forceps provided equally good results; however, the large open end of the alligator forceps often prevented distal passage through narrowing airways, engaging proximal bifurcating bronchial wall and cartilage rather than lung parenchyma. Small and large cup forceps are more likely to obtain the desired alveolar specimen.

Endobronchial tuberculosis. Serial fiberoptic bronchoscopy and natural history.

Endobronchial tuberculosis in the preantibiotic era was considered a complication of advanced post-primary disease. Bronchial mucosa adjacent to parenchymal cavities was bathed in infectious sputum, resulting in implantation. Effective antituberculosis drug therapy has reduced childhood exposure, resulting in an increase in adult primary tuberculosis with unusual clinical and roentgenographic presentations. We studied four adults with endobronchial tuberculosis who presented with unusual lobe involvement mimicking bronchogenic carcinoma. Fiberoptic bronchoscopy illustrated the range of endobronchial appearances, including evolution of mucosal ulcer to hyperplastic polyp and bronchostenosis. Complete fibrostenosis with lobar atelectasis was observed in one patient, and an eroding tuberculous lymph node in another. In the current era, endobronchial tuberculosis is more likely to be discovered in adults with progressive primary tuberculosis who have non-cavitary lower lung field infiltrates. Bronchial mucosal ulceration can result from submucosal lymphatic spread of organisms from adjacent parenchymal disease, as well as implantation.

Comparison of machine and manual staining of direct smears for acid-fast bacilli by fluorescence microscopy.

Comparisons were made in Lusaka and in London between manual staining and staining in an automatic machine with auramine-phenol of direct smears of sputum and other types of specimen for acid-fast bacilli. No evidence was obtained of carry-over of acid-fast bacilli from positive to negative smears during machine staining. There was improved contrast between bacilli and the background in smears prepared with the machine.

Electrical activity in the heart during hyperkalemic hypothermic cardioplegic arrest: site of origin and relationship to specialized conduction tissue.

Previous studies from this laboratory have shown that low-amplitude electrical activity (LEA) may occur during standard hyperkalemic hypothermic cardioplegic arrest and be undetected by routine monitoring techniques. The present study was designed to elucidate the electrophysiological nature of LEA. Ten dogs were monitored continuously during standard cardioplegic arrest using a 32-channel data acquisition system. In 7 animals (Part I), electrophysiological mapping of the lower right atrial septum during arrest was performed. The initial site of activation of LEA was consistently recorded from the region of the lower atrial septum prior to atrial or ventricular electrical activation. The site of origin of LEA was thus localized to the anatomical region of the atrial septum containing the atrioventricular nodal conduction tissue. In Part II, the electrophysiological mechanism of LEA was investigated in the remaining 3 animals utilizing an intrinsic property of specialized conduction tissue. Inclusion of a calcium channel-blocking agent in standard cardioplegic solution completely prevented the development of LEA in all 3 animals, which is in contrast to findings in previous studies using standard cardioplegic solution alone. These data suggest that LEA may be related to calcium-mediated activation of specialized conduction tissue. This mechanism of activation may explain why LEA cannot be detected by the intraoperative monitoring techniques routinely employed.

A phase I and pharmacokinetics study of 2-chlorodeoxyadenosine in patients with solid tumors.

Preclinical studies of 2-chlorodeoxyadenosine (2-CdA) against solid tumors in the human tumor cloning assay and evidence that 2-CdA is active against slow-growing or resting tumor cells have stimulated interest in the clinical activity of this agent against solid tumors. This study sought to estimate the maximum tolerated dose, dose-limiting toxicity, and plasma and urine pharmacokinetics accompanying the intravenous administration of 2-CdA by 120-h continuous infusion in patients with solid tumors. Treated patients were also assessed for other toxicities of therapy and for antitumor response. A total of 23 patients received 35 courses of treatment given at doses of 3.5, 5.3, 6.5 and 8.1 mg/m2 per day by continuous intravenous infusion for 5 days and repeated every 28 days. Blood and urine specimens were collected before, during, and after drug infusion. The dose-limiting toxicity at 8.1 mg/m2 per day manifested as granulocytopenia in 2 of 5 patients (3 of 7 courses of treatment) and as thrombocytopenia in 3 of 5 patients (3 of 7 courses of treatment). At the dose levels of 6.5 and 8.1 mg/m2 per day, recovery from thrombocytopenia was often delayed. Severe lymphocytopenia (< 1,000/microliters) was observed at all dose levels of 2-CdA. Dose-related anemia and leukopenia were observed and were infrequently severe. Non-hematological toxicities were confined to mild-to-moderate nausea, vomiting, fatigue, and anorexia. Fever of 37 degrees-40 degrees C was induced during drug infusion in 19 patients. No antitumor response was observed. Average plasma concentrations at steady-state (Cpss) ranged from 3 ng/ml at the initial dose level to 13 ng/ml at the dose level of 8.1 mg/m2 per day. Both the Cpss and the area under the plasma concentration-time curve (AUC) were proportional to the dose. A relationship was observed between the percentage of change in absolute neutrophil count and the AUC. Renal excretion accounted for only 18% of the elimination of 2-CdA over the 5-day infusion period. The maximum tolerated dose for 2-CdA given by 5-day continuous infusion was 8.1 mg/m2 per day in this study. The recommended dose on this schedule for phase II studies is 6.5 mg/m2 per day. Granulocytopenia and thrombocytopenia were dose-limiting. No antitumor activity was observed during this study. On the basis of the plasma concentrations of 2-CdA observed, it is unlikely that this schedule of drug administration will permit achievement of the concentrations consistent with antitumor activity observed in preclinical studies.

Silicon cellular morphology.

We describe a design technique for neuromorphic engineering that exploits both Mead's notion of physical equivalence between transistors and ion channels and the intrinsic properties of the materials of which transistors are composed. This is in contrast to the "algorithmic" design technique in common use. A "physical" design technique allows us to emphasise the morphology of cells. We hope to use this in an exploration of the effect of cell morphology upon function.

SPIKEII: an integrate-and-fire AVLSI chip.

We present the SPIKEII chip, an integrate-and-fire neural network chip with programmable synapses implemented in analogue VLSI. It is the successor to the SPIKEI chip. We describe the circuitry, and show some results using networks of integrate-and-fire neurons.

Athletic footwear.

The development of technical athletic footwear is based on two interrelated principles: injury prevention and enhanced performance. Most athletes are interested in and will benefit from shoes that prevent injuries. On the other hand, in many situations, competitive or elite athletes might be willing to accept the increased injury risk if the shoe can enhance performance. For these performance athletes, injury prevention may be a less important consideration. Emphasis can be placed on ultra-lightweight shoes which maximize energy return and do not restrict the desirable motions of the individual sport. Every sport demands a specific shoe. The process of new shoe development is similar to those categories already described: an understanding of the sport's biomechanics; an evaluation of the sport's injury patterns; prototype construction; wear-testing to insure fit, comfort, and playability; and manufacturing. Sports with large numbers of participants get the most attention, but lesser known sports demand the same detailed development. Softball, field hockey, boxing, and wrestling are, to name a few, sports which require specialty footwear. As our understanding improves in each sport, footwear technology and construction will follow.

Forum.

A Forum for Our Readers Forum is intended to provide a sounding board for our readers. Perhaps you have a special way to treat a common medical problem, or you may want to air your views on a controversial topic. You may object to an article that we have published, or you may want to support one. You may have a new trend to report, identified through an interesting case or a series of patients. Whatever your ideas, we invite you to send them to us. Illustrative figures are welcomed. Address correspondence to Forum, THE PHYSICIAN AND SPORTSMEDICINE, 4530 W 77th St, Minneapolis, MN 55435.

Medical Complaints After a Marathon Run in Cool Weather.

In brief: Little information is available about medical complaints after marathons held in cool weather. To obtain such information medical records were maintained on every runner requesting medical attention after the Bostonfest Marathon on Oct 30, 1983. One hundred sixty-four (11.5%) of the runners finishing the race requested medical attention at the finish line. Men and women requested attention with equal frequency, but younger (20 to 30 years old) and faster (finishing in less than 3:00) runners sought medical attention more often than the older and slower runners. The complaints and symptoms of runners after the race were similar to those of runners following warm-weather races.

Evaluation and management of the muscle contraction headache.

Headache was the seventh most frequent reason for a visit to primary care providers specified in the 1977-1978 National Ambulatory Care Survey. Muscle contraction headaches (MCH) constitute 90 percent of all headaches. Following a discussion of the epidemiology of headache, this article describes the pathophysiology, history, psychological profile of the typical MCH patient, common objective findings of MCH versus intracranial mass, physical findings and diagnosis. The management section includes a discussion of education and appropriate pharmacologic treatment, along with non-pharmacologic treatments such as massage, acupressure, biofeedback and stress management. Acupuncture is briefly described. Referral criteria for the MCH is included.

Evaluation of an educational intervention to increase cultural competence among registered nurses.

The purpose of this two group intervention study (N = 94) was to determine if RNs who participated in "culture school" improved levels of cultural competence to a greater extent than RNs who attended nursing informatics classes. The Giger and Davidhizar Transcultural Assessment Model/Theory (GDTAMT) was the study's theoretical foundation (Giger & Davidhizar, 1995). A sample of 94 participants, was identified from a randomized group of all Jefferson County, Alabama RNs. Randomly assigned participants (stratified by race) experienced 8.5 hours of either culture school or nursing informatics classes and completed survey tools in three phases (pre-intervention, immediate post intervention, three week follow-up). The Cultural Self-Efficacy Scale (CSES) by Bernal and Froman (1987), knowledge base questions by Rooda (1990), and demographic profiles were used. Concepts empirically measured using these tools were analyzed by transcultural nursing experts for their congruence with GDTAMT. Using repeated measures analyses of convariance (race), significant differences between groups for both scales were found. Culture school participants demonstrated significantly more cultural self-efficacy and cultural knowledge, and these improvements remained during phase three. Further research is recommended to allow for greater generalizability of findings, an examination of client perceptions, and actual nurse behaviors.