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.     

Two-step hard acid deprotection/cleavage procedure for solid phase peptide synthesis

A new two-step deprotection/cleavage procedure for t-butoxycarbonyl (Boc) based solid phase peptide synthesis is reported. First the protective groups are removed from 4-(oxymethyl)-phenylacetamidomethyl (PAM) resin attached peptide with the weak hard acid, trimethylsilyl bromide-thioanisole/trifluoroacetic acid (TFA). In the second step, the peptide is cleaved from the resin with a stronger hard acid such as trimethylsilvl trifluoromethanesulfonate in TFA or with HF. The method is also shown to deformylate Nⁱⁿ-formyltryptophan moiety efficiently. The usefulness of this procedure for practical solid phase peptide synthesis is demonstrated by comparison with other deprotection methods in the synthesis of urotensin II and human endothelin.     

Human T cell responses to recombinant mite antigens of Dermatophagoides farinae

We studied T cell responses to four glutathione S transferase (GST)-fused mite antigens prepared in our laboratory using peripheral blood lymphocytes from mite-sensitive patients with bronchial asthma. Of the four recombinant antigens, purified GST-Mag3 had the strongest ability to cause patients' lymphocytes to proliferate, and its potency was almost comparable to that of crude mite bodies (Dfb) and faeces (Dff) antigens and a purified major antigen, Der f 2. The responder lymphocytes were mainly T cells, because the proliferative response was depleted by the treatment of lymphocytes with anti-CD3 antibody and complement, but not with anti-CD20 antibody and complement. The responsiveness of lymphocytes to GST-Mag3 correlated with that to Der f 2, but GST-Mag3 displayed slightly higher activity to stimulate lymphocytes than Der f 2. Simultaneously, the levels of Dff- and GST-Mag3-specific IgE antibodies correlated with the responsiveness of lymphocytes to GST-Mag3. These results suggest that Mag3 is a new valuable antigen for the response of T cell proliferation in mite-sensitive patients.     

Productin of Basic Fetoprotein in Human Peripheral Lymphocytes during Blastic Transformation

To clarify the significance of basic fetoprotein (BFP) in lymphocytes, we investigated whether BFP is produced in lymphocytes during blastic transformation. Peripheral blood lymphocytes obtained from 14 adults were cultured under the stimulation of lectins. The concentration of BFP in the culture medium (extracellular BFP) was estimated serially. The incorporation of [6-³ H] thymidine was assayed simultaneously. The intracellular BFP was measured by dual flow cytometry for DNA and BFP. A lymph node was studies immunohistochemically. Serum BFP was measured in four cases of lumphocytic leukaemia. In two cases, dual staining was performed. The intracellular BFP of the mitogen-stimulated lymphocytes was increased within 24 h. The extracellular BFP was increased exponentially from 72 h. The extracellular BFP at 96 h did not correlate with the [³H]-thymidine incorporation. The intracellular BFP increase began in G₁ phase. Immunostaining showed that the B cells also produced BFP. The
serum BFP level in leukaemia was high in 1 of 4 cases and the leukaemic cells in two cases showed high intracellular BFP content. These observations indicate that BFP is produced in activated human lymphocytes and in lymphocytic leukaemic cells. The production of BFP during blastic transformation will be a useful new in vitro model for studying the biological role of BFP, and BFP labelling may offer some new possibilities for study of lymphocytes.     

Immunohistochemical Study of Serum Proteins in Normal and Cadmium-Treated Mouse Testis by in vivo CryotechniqueImmunohistochemical Study of Serum Proteins in Normal and Cadmium-Treated Mouse Testis by in vivo Cryotechnique

Objective To investigate time-dependent changes of serum proteins permeability in the normal and cadmium（Cd）-treated mouse testis, reflecting tight junctional （TJ） barriers of Sertoli cells Methods The serum proteins, albumin and immunoglobulin-G（IgG）, in the seminiferous tubules were firstly immobilized by the “in vivo cryotechnique”, in which the dynamic blood circulation was always kept. The cryofixed testicular tissues were then processed for the freeze-substitution method, and embedded in the paraffin wax. Serial sections of 5μm thickness were immunostained by anti-mouse albumin or IgG antibody with peroxidase immunostaining, and also stained with hematoxylin-eosine （HE）for morphological observation. Results In normal seminiferous tubules, albumin immunoreaction products were localized around peritubular myoid cells and among Leydig cells, as well as in blood vessels. They were also localized as arch-like patterns around some spermatogonia in basal compartments. The number of the immunopositive arch structures was different according to developmental stages of the seminiferous cycle, judging from the arrangement of germ cells by HE-staining. The patterns of localization of IgG immunostaining in normal mouse testis were similar to that of albumin. In 24 h after Cd-treatment, some enlarged spaces and vesicular formation in the seminiferous epithelium were observed on the paraffin sections by HE-staining. The albumin or IgGimmunolocalization was seen not only in the basal compartments, but also in the adluminal compartments between Sertoli.cells and germ cells. Conclusion The structural changes of inter-Sertoli TJ barriers in vivo, such as different immunostaining patterns of serum proteins between the normal and Cd-treated mouse seminiferous tubules, could be clearly detected by the “in vivo cryotechnique” with albumin or IgG immunohistochemistry.     

Adrenoleukodystrophy indicated by abnormal electroencephalography

An 8 year old boy with adrenoleukodystrophy and his asymptomatic brother, both with abnormal electro-encephalography as the initial sign of adrenoleukodystrophy, are reported. After suffering from aseptic meningitis caused by Echo virus 30, the first case was suspected of having a complication of meningitis because of persistent abnormal electro-encephalography (i.e. slow wave bursts in the occipital region). This patient was finally diagnosed as having adrenoleukodystrophy because of the increased level of very long chain saturated fatty acids, and typical occipital lesions demonstrated by magnetic resonance imaging and computed tomography. Dietary therapy was tried, but the course was progressive. The brother's electroencephalography was also abnormal and so was diagnosed as having asymptomatic adrenoleukodystrophy because of an increased level of very long chain saturated fatty acids, although brain magnetic resonance imaging was normal. Abnormal electro-encephalography can therefore be an initial sign of adrenoleukodystrophy even if magnetic resonance imaging shows no abnormality in the brain.