Biomedical subjects
S H Lim
Publications and source records attributed to S H Lim.
Lying in children.
Lying is a common problem in children. The causes of lying are numerous. With proper management including good parental role models, minimising or preventing contributing factors, and appropriate discipline, most children outgrow the tendency to lie.
Stealing in children.
Stealing is a common behavioural problem in children. The causes of stealing include a desire for possession, attention-seeking behaviour, revenge, a lack of discipline, poor parental role models, or significant psychological or psychiatric problems. With proper management, the tendency to steal resolves in most children.
Teicoplanin and prophylaxis of Hickman catheter insertions.
A total of 88 patients with haematological malignancies who required Hickman catheters for intensive chemotherapy, were randomized to receive either a single bolus intravenous injection of teicoplanin, or no teicoplanin, immediately before insertion of a double lumen Hickman catheter. There was a lower incidence of catheter-related Gram-positive sepsis in patients receiving prophylactic teicoplanin. This benefit was particularly clear in patients who were already neutropenic at the time of catheter insertion. Prophylactic teicoplanin may, therefore, be useful as a routine procedure during the insertion of Hickman catheters for this group of patients.
Counseling parents about childhood discipline.
Traditional disciplinary methods include rewards to reinforce good behavior and punishment for unacceptable behavior. Rewards may take the form of verbal praise, a smile, special attention or activities, physical affection, extra privileges or material benefits. Punishment may include verbal disapproval, an unhappy look, ignoring the behavior (extinction), temporary isolation ("time-out") or temporary removal of a privilege. Rewards are more effective than punishment. Discipline should be consistent, reasonable and appropriate to the child's age. Rules should be as few and as clear as possible. Parents should be exemplary role models for their children. Punishment, when required, should be immediate and inevitable. Punishment should be just and directed toward the undesired behavior rather than the child. Parents should discipline their children with love, understanding, patience and tolerance.
Use of intracranial neurophysiologic recording techniques in the evaluation for epilepsy surgery in children.
Resective surgery is an accepted treatment modality for medically intractable focal epilepsy in children as well as in adult. During the presurgical evaluation processes, intracranial neurophysiologic recording of epileptiform abnormalities have been used much more commonly in adults and older adolescents than in infants and children. However, as infants and children are increasingly referred for early surgery in many centres, it may be necessary to study complex cases in some children with invasive electrodes in order to plan a safe and effective resection. This article gives first an overview of the rationale and indications, with case illustrations, for using these techniques. This is followed by general discussions on individual electrodes and their use in infants and children.
Etiologic factors for unitemporal vs bitemporal epileptiform discharges.
We compared the etiologic factors and clinical characteristics of 30 patients with unitemporal vs those of 30 patients with bitemporal independent (minimum 20% from one side) interictal epileptiform discharges on extracranial electroencephalograms. Febrile seizures occurred significantly more frequently in the unitemporal (40%) than in the bitemporal (17%) group. Mass lesions were more common in the bitemporal group, and seven of 10 patients with mass lesions showed bitemporal interictal epileptiform discharges. There were no statistically significant differences in age at onset, frequency of seizures, duration of epilepsy, and history of central nervous system infection or trauma between the two groups. A history of febrile seizures or central nervous system infection that may be expected to cause diffuse cerebral injury does not appear to be the major factor predisposing to the development of bitemporal interictal epileptiform discharges.
Lymphocyte activation in patients with acute myeloid leukaemia. Evidence for the presence of myeloblast antigen?
A group of 27 patients with acute myeloid leukaemia (AML), 15 with active disease and 12 in complete remission, were investigated for evidence of T cell activation. The parameters of T cell activation measured were the serum levels of soluble interleukin-2 receptor (sIL-2R), soluble CD4 (sCD4) and soluble CD8 (sCD8) molecules and the proportions of T cells expressing the cytotoxicity-linked cytoplasmic serine esterase. All patients studied with active disease had elevated sIL-2R and sCD8 molecules and an elevated proportion of T cells expressing serine esterase. Patients studied in complete remission also had elevated sIL-2R. sCD8 and serine-esterase-positive T cells, but values were lower than those studied in active disease. These patients were all studied in the absence of any ongoing or recent infection or exposure to homologous blood products, either of which could potentially affect these parameters. In the absence of any obvious alternative cause, we suggest these data indicate that AML leukaemia blast cells may be immunogenic and lead to the activation of cytotoxic T cells.
Lymphocyte activation and serine-esterase induction following recombinant interleukin-2 infusion for lymphomas and acute leukaemias.
In this study we investigated the pattern of T lymphocyte changes in 16 adult patients with acute myeloid leukaemia (8), non-Hodgkin's lymphoma (4) and Hodgkin's disease (4) treated with continuous infusion of recombinant interleukin-2 (rIL-2). Effects indicative of lymphocyte activation occurred even prior to any rIL-2 therapy in these patients, being most prominent in patients with active diseases. Following each course of cytokine therapy, there were further changes in these parameters. Significant rebound lymphocytoses occurred with a concomitant increase in the cytotoxic functions and induction of the cytotoxicity-linked cytoplasmic serine esterase. Hence, both the natural killer and lectin-dependent cellular cytotoxicity activities were up-regulated. There were also increases in the serum sIL-2 receptor, sCD4 and sCD8 levels. More CD3+ lymphocytes, especially cells bearing CD4, were also recruited to the pool of potential effector cells, as demonstrated by the greater proportion of cells expressing the cytoplasmic serine esterase.
Cellular cytotoxic function and potential in acute myelogenous leukaemia.
Twenty-seven adult AML patients (13 with active disease and 14 in complete remission) were investigated for their cellular cytotoxic potential and function. All AML patients, whether with active disease or in complete remission, showed increased percentage of CD3+ lymphocytes expressing the cytotoxicity-linked cytoplasmic serine esterase, suggesting a higher than normal cytotoxic potential. However, when the cytotoxic function in these patients were analysed in terms of the natural killer and lectin-dependent cellular cytotoxicity, all AML patients, whether with active disease or in complete remission, had impaired target cell lytic activity. This paradox of cytotoxicity is most likely due to the immunosuppressive effect of the serum factor elaborated by leukaemia myeloblasts.
Continuous intravenous infusion of high dose recombinant interleukin 2 for advanced lymphomas--a phase II study.
The prognosis of patients with advanced refractory lymphoma remains poor. We have carried out a Phase II study of continuous high dose intravenous recombinant interleukin 2 alone without LAK cells in this group of patients. Eight patients have so far been treated, 4 with non-Hodgkins lymphoma and 4 with Hodgkins disease. Of the 7 evaluable patients, the maximum response observed was stable disease in 2 patients (1 with NHL and 1 with HD). The other patients' diseases progressed in the face of immune activation following the rIL-2 infusion. Adverse reactions were common but no life-threatening occurred. These results are disappointing. Whether or not lymphokine-activated killer (LAK) cells are needed to improve response rate deserve further investigations.
Production of tumour-derived suppressor factor in patients with acute myeloid leukaemia.
In an attempt to investigate the underlying cause of impaired cellular cytotoxic functions in patients with acute myeloid leukaemia and the relative ineffectiveness of immunotherapy with recombinant interleukin 2 (IL-2), normal donor lymphocytes were incubated in AML sera and in supernatant of myeloblasts. There was significant inhibition of both the natural killer activity and the lectin dependent cellular cytotoxicity of the normal donor lymphocytes compared to when incubation took place in autologous or normal allogeneic sera or marrow supernatant. This inhibition was time-related and partially reversible by washing of the normal lymphocytes immediately before the cytotoxicity assay. The suppressor factor, however, did not inhibit the IL-2 induced lymphocyte proliferation or affect the cytotoxicity-linked cytoplasmic serine esterase expression in the normal lymphocytes. This suppressor phenomenon was of myeloblast origin. Chronic exposure to the tumour-derived suppressor factor may be responsible for the impaired cellular cytotoxic functions observed in patients with acute myeloid leukaemia. It may also suppress the in vivo cytotoxic functions of IL-2 activated lymphocytes in patients treated with recombinant IL-2, hence leading to the disappointing results of immunotherapy so often encountered in clinical setting.
A prospective randomized study of prophylactic teicoplanin to prevent early Hickman catheter-related sepsis in patients receiving intensive chemotherapy for haematological malignancies.
Eighty-eight patients with haematological malignancies requiring Hickman catheters for intensive chemotherapy were randomized to receive either one single bolus intravenous injection of teicoplanin or no teicoplanin immediately before insertion of a double lumen Hickman catheter. There were lower incidences of catheter-related Gram-positive sepsis in patients receiving prophylactic teicoplanin. There were less exit site infections, tunnel infections and catheter-related Gram-positive septicaemia. The benefit of prophylactic teicoplanin was observed especially among patients who were already neutropenic at the time of catheterization. All Gram-positive organisms isolated from the infected skin sites or from blood cultures taken from the Hickman catheters were sensitive to teicoplanin. No adverse reaction was reported in any of the patients in the prophylactic group. Prophylactic teicoplanin therefore may be used routinely for patients requiring insertion of Hickman catheters for intensive chemotherapy to reduce the early incidence of catheter-related sepsis, especially during the associated period of neutropenia following chemotherapy.
Thyroid disorders in 2 cases of acute myeloid leukaemia following treatment with recombinant interleukin-2 infusion.
Two AML patients treated with recombinant interleukin-2 infusion without LAK cells developed thyroid complications within 2 months following the treatment. One patient was clinically and biochemically hypothyroid but was negative for thyroid autoantibodies while the other patient developed thyroid microsomal autoantibody but remained euthyroid. These 2 cases represent the two ends of the spectrum of thyroid complications following interleukin-2 therapy. Such complications are not uncommon but are poorly documented. We suggest that patients receiving cytokine therapy should be followed up closely for any autoimmune complications.
Bacterial infections in lymphoma patients treated with recombinant interleukin-2.
10 lymphoma patients given a total of 26 courses of intravenous continuous infusion of recombinant interleukin-2 (rIL-2) alone without lymphokine-activated killer cells were analysed retrospectively for the frequency and pattern of bacterial infections associated with the immunotherapy. 4 episodes of septicaemia and 7 episodes of soft tissue infections resulted from the 26 courses of rIL-2 infusion. Although there was no death due to infection, all these infections were clinically significant, needing systemic antibiotic therapy and resulting in prolonged hospitalisation. Gram-positive infections occurred significantly (p less than 0.001) more often than gram-negative infections. Patients with non-Hodgkin's lymphoma had a higher incidence of infection than patients treated for Hodgkin's disease, analysed either as infection per patient treated (p less than 0.05) or infection per course of rIL-2 given (p less than 0.02).
Prophylactic teicoplanin during insertion of Hickman catheters.
With the extensive use of Hickman catheters in patients requiring cytotoxic chemotherapy there is now a resurgence of Gram-positive septicaemia among these patients during the neutropenic periods. We are currently running a prospective randomized study of prophylactic teicoplanin during insertion of Hickman catheters to determine if it reduces the incidence of Gram-positive septicaemia. A total of 44 patients have completed the study (23 in the teicoplanin group and 21 in the control group). The diagnoses were: acute myelogenous leukaemia (13), non-Hodgkin's lymphoma (16), Hodgkin's disease (11), chronic granulocytic leukaemia (3) and acute lymphoblastic leukaemia (1). The number of days between insertion of Hickman catheters and the development of neutropenia was: teicoplanin group: mean 14.7, median 11, range 0-53; control group: mean 11.8, median 10, range 0-37. In the treated patients, there were four episodes of line-associated Gram-positive septicaemia and a total of four organisms were isolated. In the control group, 10 organisms were isolated from a total of nine episodes of line-associated Gram-positive septicaemia. The organisms were: coagulase-negative staphylococci (8), Streptococcus B, (1), Strep. faecalis (1), Strep. mitis (1), alpha streptococcus (1), diphtheriods (1) and Staphylococcus aureus (1). All organisms were sensitive to teicoplanin. No adverse reaction was observed in any patient. Prophylactic teicoplanin during insertion of Hickman catheters may therefore reduce the incidence of line-associated Gram-positive septicaemia in neutropenic patients.
A randomized prospective study of ceftazidime and ciprofloxacin with or without teicoplanin as an empiric antibiotic regimen for febrile neutropenic patients.
Febrile neutropenic patients were randomized to receive ceftazidime and ciprofloxacin with the addition of teicoplanin in cases with clinical suspicion of a Hickman line-associated infection. At 48 h both clinical and bacteriological analyses were made. Patients were categorized as: success, in cases of improvement or stability in the clinical condition; failure, if there was a deterioration of the clinical condition; and non-evaluable, in cases of protocol violation or death due to other causes. A total of 86 patients have completed the study so far; 43 patients were randomized to the ceftazidime and 43 to the ciprofloxacin group. Teicoplanin was added to the monotherapy in 12 patients in the ceftazidime group and 15 in the ciprofloxacin group. The diagnoses were: acute myelogenous leukaemia (25), non-Hodgkin's lymphoma (34), Hodgkin's disease (17); acute lymphoblastic leukaemia (9) and chronic granulocytic leukaemia (1). Forty-eight hour clinical assessment showed a response rate in the ceftazidime group of: success 18/31 (58%), failure 13/31 (42%); in the ceftazidime and teicoplanin group: success 8/12 (67%), failure 4/12 (33%); in the ciprofloxacin group: success 23/28 (82%), failure 5/28 (18%); and in the ciprofloxacin and teicoplanin group: success 11/15 (73%), failure 4/15 (27%). Blood cultures were positive in 48/86 (56%) cases, with more than one organism isolated in seven of these 48 cases. Organisms isolated were: coagulase-negative staphylococci (20), Escherichia coli (13), Pseudomonas aeruginosa (4), Staphylococcus aureus (3), diphtheroids (3), Klebsiella sp. (3), Enterobacter cloacae (2), Streptococcus faecalis (2), Ent. adenocarboxylata (1), Clostridium septicum (1). Strept. B (1), alpha streptococcus (1) and P. fluorescens (1), In-vitro testing showed that all Gram-positive organisms were sensitive to teicoplanin, and Gram-negative organisms to ciprofloxacin or ceftazidime. There were seven cases of superimposed infections with eight organisms isolated, all cases occurring in patients receiving ciprofloxacin alone: coagulase-negative staphylococci (4), Strep. sangius (1), Strep. viridans (1), diphtheroids (1) and P. maltophilia (1). Both ciprofloxacin and ceftazidime are comparable in efficacy as empirical monotherapy for febrile neutropenic patients. There is, however, a significant increase in the incidence of superimposed infection in patients receiving only ciprofloxacin. In view of the very high incidence of Gram-positive septicaemia, we suggest that teicoplanin should be added as part of the initial empiric antibiotic regimen in all febrile neutropenic patients.
Yields of fibronectin by heparin-cold-precipitation from plasma.
Fibronectin prepared by heparin-cold-precipitation from 10 packs each of 24-hour plasma, stored plasma and 6-hour frozen plasma was assayed by electroimmunodiffusion. Its yield obtained from 24-hour plasma was significantly higher than that from stored plasma (p less than 0.01) indicating a decline with storage. Freezing of plasma within 6 hours retards degradation of fibronectin. Therefore, 24-hour plasma or 6-hour frozen plasma should be used to prepare fibronectin in order to achieve a better yield.