Analysis of the circumstances at the end of life in children with cancer: Symptoms, suffering and acceptance

BACKGROUND: In an effort to improve the quality of life of children with cancer, this study analyzes the signs and symptoms at the end of life in such children. It is hoped that these data will contribute to the development of appropriate programs to address the challenges faced by these children. PROCEDURE: Between 1994 and 2000, 28 children died after treatment for cancer at Hamamatsu University Hospital, Japan. The circumstances, signs and symptoms at the end of life of these children were analyzed through their medical records. RESULTS: Of the 28 children, the underlying diseases were leukemia/lymphoma (LL group; n=11), brain tumors (BT group; n=7), and other solid tumors (OST group; n=10). Records showed poor appetite (100%), dyspnea (82.1%), pain (75.0%), fatigue (71.4%), nausea/vomiting (57.1%), constipation (46.4%) and diarrhea (21.4%) among these children. Anxiety was reported in 53.6% of the entire group of 28 children; however, no child in the BT group manifested anxiety. However, disturbance of consciousness was reported in all children in the BT group, which was significantly greater than in the other groups. Awareness, fear or acceptance of the imminence of his/her own death as indicated by verbal expression was reported in nine children (32.1%). CONCLUSIONS: Using the data obtained in the present study, we describe situations faced in the terminal care of children. It is important to address the problems revealed by this analysis in order to achieve improvements in both the physical and psychological care of children with terminal cancer.     

Evaluation of Survival Rates and Number of Patients with Malignant Neoplasms Surviving for a Long Time after Treatment at the National Cancer Center Hospital

Since 1962, the National Cancer Center Hospital has been activein the medical care of cancer patients. Also, it has conductedcancer registration and collected information on cancer patients.According to the data collected, survival rates, as well asstatistics tables, were calculated. The 5-yr survival rates for patients admitted to the hospitalshow an increasing trend for cancer in many sites. Consequently,the overall 5-yr survival rates for patients with malignantneoplasms have risen. They are 36.65% in males and 59.81% infemales for patients admitted in the period from 1975 to 1980. The progress in diagnosis and treatment of cancer has broughtan increase in the number of long-term survivors among cancerpatients. According to the statistics of 1983, the number ofpatients surviving 5 yr or more after treatment at the NationalCancer Center Hospital was 8,193, for lOyr or more it was 3,717and for I5yr or more it was 1,412.     

Lack of an Effect of Madopar on the Disposition of Tolcapone and its 3-O-Methylated Metabolite in Rats

The effect of Madopar (benserazide and l -dopa, 1:4) on the disposition of the new selective inhibitor of catechol-O-methyltransferase, tolcapone, in rats was investigated. There was no statistically significant difference in the pharmacokinetic parameters of tolcapone in the presence or absence of Madopar except for a change in the mean residence time after oral administration. Thus, we rejected the hypothesis that the consumption of S-adenyl-l -methionine by Madopar would change the disposition of tolcapone. There were no statistically significant differences in the cumulative amount absorbed of drug and the absorption rate in the presence or absence of Madopar. We concluded that there was no interaction between tolcapone and Madopar.     

Acidosis and raised norepinephrine levels are associated with exercise dyspnoea in idiopathic pulmonary fibrosis

Background and objective:   Exertional dyspnoea limits patients with IPF in their activities of daily living. The mechanism, however, has not been elucidated. This study tested the hypothesis in IPF that exertional dyspnoea correlates with cardiopulmonary exercise responses, specifically changes in arterial blood pH and plasma norepinephrine (NE).
Methods:   Cardiopulmonary exercise testing with measurements of dyspnoea (Borg scale), plasma NE, plasma lactate and arterial blood gases were performed in 29 patients with IPF and in nine controls.
Results:   Both groups showed obvious break points in dyspnoea changes during exercise. In IPF, an abrupt change in the Borg scale, pH, PaCO₂ and plasma NE occurred in the late exercise phase after the 'break point'. Compared with controls, patients with IPF had significantly higher HCO₃^- levels and physiologic dead space/tidal volume during exercise. In IPF, during both exercise phases, the dyspnoea slope (ΔBorg scale/Δminute ventilation) correlated with the pH slope (ΔpH/Δoxygen uptake) (before the break point: r  = −0.537, P  = 0.0022; r  = −0.886, P  < 0.0001, after the break point) and the NE slope (ΔNE/Δoxygen uptake) (before the break point: r  = 0.481, P  = 0.0075; R  = 0.784, P  < 0.0001, after the break point).
Conclusions:   In patients with IPF, exercise-induced acidosis and increases in circulating NE levels were associated with intensity of exertional dyspnoea.     

The Disposition of the Tolcapone 3-O-Methylated Metabolite is Affected by the Route of Administration in Rats

Abstract— Catechol-O-methyltransferase (COMT) catalyses the transfer of the methyl group from S-adenyl-l -methionine (SAM) to one of the hydroxy groups of a catechol, usually the hydroxy group in position 3. COMT is present mainly in a soluble form (S-COMT) in the cytosol, but a small fraction is bound to cell membranes (MB-COMT). MB-COMT has higher affinity for the catechol substrate than does S-COMT by a factor of > 10, and high MB-COMT activity is observed in the intestinal muscle layer. The present study investigates the effect of the administration route on the disposition of the tolcapone 3-O-methylated metabolite following intravenous and oral tolcapone administration in rats. Tolcapone is a substrate for COMT although the 3-O-methylated metabolite produced has no pharmacological actions. The 3-O-methylated metabolite was eliminated very slowly following oral administration of tolcapone, and its concentration approached a plateau level, which was in contrast to the situation following intravenous administration of tolcapone. It is thought that the oral dose of tolcapone receives a high exposure to MB-COMT in the intestinal muscle layer during its absorption, and tolcapone seems to form a complex with MB-COMT having a high affinity constant (i.e. a very low K_i). The fraction of the intravenous dose of tolcapone metabolized to the 3-O-methylated metabolite at 10 mg kg^?1 was 2·6%, whereas those of the oral doses, which were corrected by the bioavailability, were 5·4% for 20 mg kg^?1 and 2·7% for 40 mg kg^?1.     

Chromosome Analysis in Preimplantation Stage Embryos of Non-Obese Diabetic (NOD) Mice

Abstract Congenital malformations such as exencephaly occur at a high incidence in non-obese diabetic (NOD) mouse embryos (Otani et al., 1987a). Using in vitro culture and embryo transfer, genetic predispositions as well as environmental factors were suggested to be the causes (Tatewaki et al., 1987).
Chromosomes of preimplantation embryos, cultured to transfer mutually between non-obese diabetic (NOD) and ICR mice, were analyzed as a clue to elucidate the cause of developmental anomalies. Among these preimplantation embryos, aneuploidy, mixoploidy and structural anomalies were found, but in incidence of chromosomal anomalies there was no significant difference, statistically, between preimplantation embryos from diabetic mothers and those from non-diabetic mothers. These findings are considered to show that no increase in developmental abnormality in chromosomes occurs during the preimplantation stage.     

Analysis of the circumstances at the end of life in children with cancer: A single institution''s experience in Japan

BACKGROUND: With the aim of improving the quality of life of children with cancer, this study presents an analysis of one hospital's experience with terminal care. METHODS: Between 1994 and 2000, 28 children died after treatment for cancer at Hamamatsu University Hospital. The circumstances of their deaths were analyzed through medical records and interviews with 8 sets of bereaved parents. We compared results of this analysis with our previous data collected from 1978 to 1993. RESULTS: Of the 28 children, 11 had leukemia/lymphoma (LL group) and 17 had solid tumors (ST group). Six children (21.4%), all of whom were in the LL group, died of treatment-related complications. Twenty children (71.4%) died during terminal care: three (27.3%) were in the LL group and 17 (100%) in the ST group. Eleven children (39.3%) received terminal care at home and eight (28.6%) of these died at home. The number of children who received terminal care and died at home had increased in comparison with the previous period. Among problems with terminal care identified by parents were the lack of opportunity for the child to continue with education and an inadequate support system after the child's death. CONCLUSIONS: Some advances in the quality of life of the children were recognized. However, these advances were extended to a greater percentage of children in the ST group than in the LL group. The psychosocial problems faced by children and their families are now changing for the better.     

Fluorescent Substances and High Molecular Weight Protein Aggregates Formed in Rat Heart Mitochondria upon Doxorubicin-induced Lipid Peroxidation

A rat heart mitochondrial suspension was incubated with doxorubicin, FeCl₃ and NADH. Fluorescent substances and high molecular weight protein aggregates were observed in the mitochondrial membranes upon the formation of thiobarbituric acid-reactive substances. Since both fluorescent substances and high molecular weight protein aggregates are retained in mitochondrial membranes, they can be of use in the clarification of the site of doxorubicin-induced lipid peroxidation.     

On-line haemodiafiltration: Effective removal of high molecular weight toxins and improvement in clinical manifestations of chronic haemodialysis patients

Summary: The aim of this study was to validate the purity of the injection fluid in an on-line haemodiafiltration (HDF) system, and to investigate whether the aggressive removal of high molecular weight toxins achieved by the on-line HDF will reduce symptoms such as shoulder pain and pruritus. the dialysate for substitution use contained no endotoxin, β-D-glucan, or peptidoglycan, suggesting that contamination with gram-negative/positive bacteria and fungi are kept clear or at extremely low levels. No deleterious complications occurred during the on-line HDF treatments. the improvement in shoulder pain and pruritus indicated by a decrease in patients' self-rating scores, was more apparent with treatment that removed both β2-microglobulin (β2-m) and α1-microglobulin (α-m) than with treatment removing either β2-m or α1-m alone. On-line HDF is much easier to operate and less costly than conventional HDF, and it may become one of the standard therapies for chronic renal failure patients.     

Pituitary adenylate cyclase activating polypeptide (PACAP) with 27 residues

The conformation of pituitary adenylate cyclase activating polypeptide with 27 residues (PACAP27) has been determined by two-dimensional NMR and CD spectroscopies and distance geometry in 25% methanol. Residues 9-20 and 22-25 have well-defined conformations but other residues do not show ordered conformations. The conformation of residues 9-20 is composed of three distinct regions of β turn-like conformation (residues 9-12), α helix (residues 12-14) and the looser helical conformation (residues 15-20), while residues 22-24 form α helix. PACAP27 has a 2 helices separated by a disordered region similar to a VIP analog reported by Fry et al. but is distinct from the VIP analog in the position of the first helix, which is shifted by 2 residues toward the C-terminus, and in the form of the second helix [Fry, D.C., Madison, V.S., Bolin, D.R., Greeley, D.N., Toome, V. and Wegrzynski, B.B. (1989) Biochemistry 28 , 2399-2409].