Peripheral blood stem cell mobilization and apheresis: analysis of adverse events in 94 normal donors.
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Adverse events were analyzed in 94 normal donors who underwent PBSC harvest with G-CSF. The median dose of G-CSF was 9.7 microg/kg/day (range, 2.0-16.7), and the duration of administration was 4-6 days. Frequent symptoms were bone pain (71%), general fatigue (33%), headache (28%), insomnia (14%), anorexia (11%), nausea and/or vomiting (11%). One donor (1%) developed grade 3 toxicity bone pain (WHO criteria). WBC counts and ANC increased during G-CSF administration. After leukapheresis, three donors (3%) developed grade 3 toxicity neutropenia. Platelet counts decreased after leukapheresis. Three donors (3%) developed grade 3 thrombocytopenia. The means of both ALP and LDH increased approximately 1.9-fold compared with pretreatment levels. In one pediatric donor (1%), ALP was elevated to the grade 3 toxicity level. From multivariate analysis, the incidence of bone pain increased when G-CSF was given at a dose of 8.8 microg/kg/day or more, headaches were frequent in donors younger than 35 years, and the incidence of nausea and/or vomiting was high in female donors. The peak levels of WBC counts and ANC and post-treatment level of LDH increased in correspondence with the escalation of G-CSF dose. All adverse events normalized on follow-up evaluation. In conclusion, although PBSC harvest for normal donors is acceptable, care must be taken for all donors in terms of their sex and age as well as the G-CSF dose. We recommend less than 8.8 microg/kg/day as the G-CSF dose for PBSC mobilization in normal donors. (+info)
Creatine supplementation increases muscle total creatine but not maximal intermittent exercise performance.
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This study investigated creatine supplementation (CrS) effects on muscle total creatine (TCr), creatine phosphate (CrP), and intermittent sprinting performance by using a design incorporating the time course of the initial increase and subsequent washout period of muscle TCr. Two groups of seven volunteers ingested either creatine [Cr; 6 x (5 g Cr-H(2)O + 5 g dextrose)/day)] or a placebo (6 x 5 g dextrose/day) over 5 days. Five 10-s maximal cycle ergometer sprints with rest intervals of 180, 50, 20, and 20 s and a resting vastus lateralis biopsy were conducted before and 0, 2, and 4 wk after placebo or CrS. Resting muscle TCr, CrP, and Cr were unchanged after the placebo but were increased (P < 0.05) at 0 [by 22.9 +/- 4.2, 8.9 +/- 1.9, and 14.0 +/- 3.3 (SE) mmol/kg dry mass, respectively] and 2 but not 4 wk after CrS. An apparent placebo main effect of increased peak power and cumulative work was found after placebo and CrS, but no treatment (CrS) main effect was found on either variable. Thus, despite the rise and washout of muscle TCr and CrP, maximal intermittent sprinting performance was unchanged by CrS. (+info)
Skeletal muscle energy metabolism during prolonged, fatiguing exercise.
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A depletion of phosphocreatine (PCr), fall in the total adenine nucleotide pool (TAN = ATP + ADP + AMP), and increase in TAN degradation products inosine 5'-monophosphate (IMP) and hypoxanthine are observed at fatigue during prolonged exercise at 70% maximal O(2) uptake in untrained subjects [J. Baldwin, R. J. Snow, M. F. Carey, and M. A. Febbraio. Am. J. Physiol. 277 (Regulatory Integrative Comp. Physiol. 46): R295-R300, 1999]. The present study aimed to examine whether these metabolic changes are also prevalent when exercise is performed below the blood lactate threshold (LT). Six healthy, untrained humans exercised on a cycle ergometer to voluntary exhaustion at an intensity equivalent to 93 +/- 3% of LT ( approximately 65% peak O(2) uptake). Muscle biopsy samples were obtained at rest, at 10 min of exercise, approximately 40 min before fatigue (F-40 =143 +/- 13 min), and at fatigue (F = 186 +/- 31 min). Glycogen concentration progressively declined (P < 0.01) to very low levels at fatigue (28 +/- 6 mmol glucosyl U/kg dry wt). Despite this, PCr content was not different when F-40 was compared with F and was only reduced by 40% when F was compared with rest (52. 8 +/- 3.7 vs. 87.8 +/- 2.0 mmol/kg dry wt; P < 0.01). In addition, TAN concentration was not reduced, IMP did not increase significantly throughout exercise, and hypoxanthine was not detected in any muscle samples. A significant correlation (r = 0.95; P < 0. 05) was observed between exercise time and glycogen use, indicating that glycogen availability is a limiting factor during prolonged exercise below LT. However, because TAN was not reduced, PCr was not depleted, and no correlation was observed between glycogen content and IMP when glycogen stores were compromised, fatigue may be related to processes other than those involved in muscle high-energy phosphagen metabolism. (+info)
Improvement in Castleman's disease by humanized anti-interleukin-6 receptor antibody therapy.
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Castleman's disease, an atypical lymphoproliferative disorder, can be classified into 2 types: hyaline-vascular and plasma cell types according to the histologic features of the affected lymph nodes. The plasma cell type is frequently associated with systemic manifestations and is often refractory to systemic therapy including corticosteroids and chemotherapy, particularly in multicentric form. Dysregulated overproduction of interleukin-6 (IL-6) from affected lymph nodes is thought to be responsible for the systemic manifestations of this disease. Therefore, interference with IL-6 signal transduction may constitute a new therapeutic strategy for this disease. We used humanized anti-IL-6 receptor antibody (rhPM-1) to treat 7 patients with multicentric plasma cell or mixed type Castleman's disease. All patients had systemic manifestations including secondary amyloidosis in 3. With the approval of our institution's ethics committee and the consent of the patients, they were treated with 50 to 100 mg rhPM-1 either once or twice weekly. Immediately after administration of rhPM-1, fever and fatigue disappeared, and anemia as well as serum levels of C-reactive protein (CRP), fibrinogen, and albumin started to improve. After 3 months of treatment, hypergammaglobulinemia and lymphadenopathy were remarkably alleviated, as were renal function abnormalities in patients with amyloidosis. Treatment was well tolerated with only transient leukopenia. Histopathologic examination revealed reduced follicular hyperplasia and vascularity after rhPM-1 treatment. The pathophysiologic significance of IL-6 in Castleman's disease was thus confirmed, and blockade of the IL-6 signal by rhPM-1 is thought to have potential as a new therapy based on the pathophysiologic mechanism of multicentric Castleman's disease. (Blood. 2000;95:56-61) (+info)
Sequelae of sarin toxicity at one and three years after exposure in Matsumoto, Japan.
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In order to clarify the later sequelae of sarin poisoning that occurred in Matsumoto City, Japan, on June 27, 1994, a cohort study was conducted on all persons (2052 Japanese people) inhabiting an area 1050 meters from north to south and 850 meters from east to west with the sarin release site in the center. Respondents numbered 1237 and 836 people when surveys were conducted at one and three years after the sarin incident, respectively. Numbers of persons with symptoms of sarin toxicity were compared between sarin victims and non-victims. Of the respondents, 58 and 46 people had symptoms associated with sarin such as fatigue, asthenia, shoulder stiffness, asthenopia and blurred vision at both points of the survey, respectively. The prevalences were low; some complained of insomnia, had bad dreams, difficulty in smoking, husky voice, slight fever and palpitation. The victims who had symptoms one year after the incident had a lower erythrocyte cholinesterase activity than did those who did not have symptoms at the early stage; such persons lived in an area with a 500 meter long axis north east from the sarin release site. The three-year cohort study clearly showed that the odds ratios of almost all of the symptoms were high in the sarin-exposed group, suggesting a positive relationship between symptoms and grades of exposure to sarin. These results suggest that symptoms reported by many victims of the sarin incident are thought to be sequelae related to sarin exposure. (+info)
The course of anxiety and depression during the first year after allogeneic or autologous stem cell transplantation.
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Psychological distress is frequently reported in transplant survivors. We prospectively assessed anxiety and depression before transplant, in the isolation period and during a follow-up period of 1 year. The Hospital Anxiety and Depression Scale (HADS) was administered to 131 cancer patients treated with high-dose chemotherapy followed by allogeneic (SCT) or autologous (ASCT) stem cell transplantation, and a concurrent group of 123 lymphoma patients receiving standard chemotherapy (CT) who served as a reference group. Relatively low levels of anxiety and depression were found. The level of anxiety slightly declined from baseline during follow-up (mean scores SCT: from 5.3 to 3.6, CT: from 6.0 to 4.2) or remained fairly stable (ASCT: from 5.4 to 4.8). The level of depression peaked when the transplant patients were in protective isolation or shortly thereafter (SCT: 6.1, ASCT: 6.4), but stabilized at baseline levels after 4 months. The highest level of depression in the CT group was reported 4 months after start of chemotherapy (3.4). Elevated levels of anxiety and depression at baseline predicted more anxiety and depression at the later assessments (P values < 0.0001). The ASCT group had higher levels of anxiety after 1 year (mean 4.8) than those found in the other two groups (SCT: 3.6, CT: 4.2), although they were not statistically significant. This study revealed lower than expected levels of anxiety and depression after intensive chemotherapy followed by SCT or ASCT. There was a decline in psychological distress during the 1-year follow-up period. (+info)
Quantifying the performance impairment associated with fatigue.
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The present study systematically compared the effects of fatigue and alcohol intoxication on a range of neurobehavioural tasks. By doing so, it was possible to quantify the performance impairment associated with fatigue and express it as a blood alcohol impairment equivalent. Twenty-two healthy subjects aged 19-26 years participated in three counterbalanced conditions. In the sustained wakefulness condition, subjects were kept awake for 28 h. In the alcohol and placebo conditions, subjects consumed either an alcoholic or non-alcoholic beverage at 30 min intervals, until their blood alcohol concentration reached 0.10%. In each session, performance was measured at hourly intervals using four tasks from a standardised computer-based test battery. Analysis indicated that the placebo beverage did not significantly effect mean relative performance. In contrast, as blood alcohol concentration increased performance on all the tasks, except for one, significantly decreased. Similarly, as hours of wakefulness increased performance levels for four of the six parameters significantly decreased. More importantly, equating the performance impairment in the two conditions indicated that, depending on the task measured, approximately 20-25 h of wakefulness produced performance decrements equivalent to those observed at a blood alcohol concentration (BAC) of 0.10%. Overall, these results suggest that moderate levels of fatigue produce performance equivalent to or greater than those observed at levels of alcohol intoxication deemed unacceptable when driving, working and/or operating dangerous equipment. (+info)
Symptoms and suffering at the end of life in children with cancer.
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BACKGROUND: Cancer is the second leading cause of death in children, after accidents. Little is known, however, about the symptoms and suffering at the end of life in children with cancer. METHODS: In 1997 and 1998, we interviewed the parents of children who had died of cancer between 1990 and 1997 and who were cared for at Children's Hospital, the Dana-Farber Cancer Institute, or both. Additional data were obtained by reviewing medical records. RESULTS: Of 165 eligible parents, we interviewed 103 (62 percent), 98 by telephone and 5 in person. The interviews were conducted a mean (+/-SD) of 3.1+/-1.6 years after the death of the child. Almost 80 percent died of progressive disease, and the rest died of treatment-related complications. Forty-nine percent of the children died in the hospital; nearly half of these deaths occurred in the intensive care unit. According to the parents, 89 percent of the children suffered "a lot" or "a great deal" from at least one symptom in their last month of life, most commonly pain, fatigue, or dyspnea. Of the children who were treated for specific symptoms, treatment was successful in 27 percent of those with pain and 16 percent of those with dyspnea. On the basis of a review of the medical records, parents were significantly more likely than physicians to report that their child had fatigue, poor appetite, constipation, and diarrhea. Suffering from pain was more likely in children whose parents reported that the physician was not actively involved in providing end-of-life care (odds ratio, 2.6; 95 percent confidence interval, 1.0 to 6.7). CONCLUSIONS: Children who die of cancer receive aggressive treatment at the end of life. Many have substantial suffering in the last month of life, and attempts to control their symptoms are often unsuccessful. Greater attention must be paid to palliative care for children who are dying of cancer. (+info)