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Biomedical subjects

K P Windebank

Publications and source records attributed to K P Windebank.

At least 19 recordsLinked to original sources
PubMed2005

Follicular dendritic cell tumour in a 9-year-old child.

Follicular dendritic cell tumour (FDCT) or sarcoma is a rare tumour first described in 1986. Some 80 cases have been reported, the youngest being in teenagers. Our patient first presented at 9 years of age with a cervical mass that was removed and revealed an apparently benign, but florid reactive process. At age 14 the lump recurred and biopsy was diagnostic of FDCT. Radical block dissection showed disease to level III and 6 weeks of radiotherapy was followed by 6 months adjuvant chemotherapy. Three years after completing his final treatment he shows no signs of recurrent disease.

Child↗
PubMed2005

A comparison of self-reported satisfaction between adolescents treated in a "teenage" unit with those treated in adult or paediatric units.

BACKGROUND: Despite recommendations that adolescents should have in-patient management amongst their peers, there is little literature to support this. The study aim was to evaluate and contrast patient satisfaction for teenage cancer patients treated in two settings. The first is a split site unit (a paediatric ward and adult cancer centre in different locations within one city) and the second, a dedicated adolescent unit for patients aged 13-20. PROCEDURE: Eligible patients aged 13-20 years received treatment from September 1997 to June 2000 and totalled sixty-five adolescents. The patients were identified at both centres from departmental databases. Postal questionnaires (the Youth Satisfaction Questionnaire) were sent to those eligible. RESULTS: Patients receiving treatment in the teenage cancer unit (TCU) were not significantly more satisfied overall than those receiving treatment in adult or paediatric units. However, significant differences were noted in: recreational and relaxation facilities (P < 0.005, P < 0.0002), studying space (P < 0.004), ward noise (P < 0.02), and company of the same age (P < 0.0001). The Grade Point Average (a score of all specific items) was higher in favour of the TCU (P < 0.03). Patients at both centres were dissatisfied with hospital food and menus offered. CONCLUSIONS: Adolescents with cancer are satisfied with the overall care they receive independent of whether it is a TCU or a split site unit. Teenagers are significantly more satisfied with environmental aspects of care in the TCU. More research is required to establish the correct provision for teenagers with cancer. This is the first study that contrasts satisfaction between different centres and thus adding to an understanding of the needs of teenagers with cancer.

Adolescent↗
PubMed2004

Demographic study of leukaemia presenting within the first 3 months of life in the Northern Health Region of England.

AIMS: To determine the incidence and outcome of congenital leukaemia. METHODS: Retrospective population based study of putative leukaemia arising during the first 3 months of life over an 18 year period within the Northern Health Region of England. RESULTS: Nine infants with putative leukaemia were identified. Five had acute leukaemia and four had transient myeloproliferative disorder (TMD). Trisomy 21, either as Down's syndrome or perhaps restricted to proliferating marrow cells, was present in all four infants with TMD. The incidence of congenital acute leukaemia was 8.6/10(6) live births/year, but would be less than half this value if only patients presenting within 4 weeks of birth were counted. Remission was induced in three of the five patients with acute leukaemia. One patient, who presented at birth, remains well five years after diagnosis. All four patients with TMD survive. CONCLUSIONS: Congenital leukaemia is very rare but is not inevitably fatal. Finding trisomy 21 in spontaneously dividing blood or bone marrow cells of an infant with putative acute leukaemia, particularly within 3 months of birth, should encourage a cautious clinical approach and suggests that the diagnosis might be TMD.

Acute Disease↗
PubMed1999

Posttransplantation B lymphoblastic leukemia with Burkitt-like features.

BACKGROUND: Posttransplantation Epstein-Barr virus-associated lymphoproliferative disease (PTLPD) occurs as a spectrum of disease ranging from benign, polyclonal, localized lymphoid hyperplasia to malignant, monoclonal, disseminated lymphoma, sometimes involving the bone marrow. To our knowledge, PTLPD has not been previously reported to present as acute lymphoblastic leukemia. METHODS: We report the case of a boy who developed PTLPD in the form of acute lymphoblastic leukemia 6 years after cardiac transplantation. He had greater than 90% bone marrow invasion by Epstein-Barr virus-positive B lymphoblasts with Burkitt-like features and a t(8;14) translocation. RESULTS: He was successfully treated with combination chemotherapy but unfortunately died, 6 months after completing treatment, from ischemic heart disease. CONCLUSIONS: B lymphoblastic leukemia may occur as a manifestation of PTLPD and should be included in the classification of these diseases. Bone marrow examination should be an essential part of the investigation of patients suspected of having PTLPD.

Administration, Oral↗
PubMed1997

Recurrent pneumomediastinum and pneumothorax in Langerhans cell histiocytosis.

Pneumothorax is an unusual complication of pulmonary Langerhans cell histiocytosis. We report three children who developed recurrent intrathoracic air leaks. In one case, bilateral pneumothoraces may have been precipated by intermittent positive pressure ventilation during general anaesthesia. Chemical pleurodesis was unsuccessful in preventing recurrence of pneumothoraces in two children. The use of extracorporeal membrane oxygenation as an alternative to intermittent positive pressure ventilation in children with respiratory failure from Langerhans cell histiocytosis is discussed.

Adolescent↗
PubMed1997

Central venous catheter use in UKCCSG oncology centres. United Kingdom Children's Cancer Study Group and the Paediatric Oncology Nursing Forum.

A cross sectional audit of central venous catheter (CVC) use was performed in United Kingdom Children's Cancer Study Group oncology centres. There were wide variations in choice of line, insertion technique, aftercare practice, and diagnosis of CVC related sepsis. These variations highlight the difficulty in interpretation of published data on CVC efficacy.

Bacterial Infections↗
PubMed1996

Successful treatment of non-familial haemophagocytic lymphohistiocytosis with interferon and gammaglobulin.

Two cases of non-familial haemophagocytic lymphohistiocytosis (HLH) are presented in which treatment with interferon alfa and gammaglobulin was associated with complete clinical remission. In one case, serological evidence of recent Epstein-Barr virus infection was found. Natural killer cell activity was within normal limits in both children, compatible with a secondary form of HLH. The combination of interferon alfa and intravenous gammaglobulin requires further evaluation in the treatment of non-familial HLH.

Cytotoxicity, Immunologic↗
PubMed1995

Flow cytometric determination of intracellular calcium changes in human peripheral blood mononuclear cells during conjugation to tumour cell lines.

Using a flow cytometric assay, conjugate formation between human peripheral blood mononuclear cells (PBMC) and three different human tumour cell lines has been analysed. Changes in the intracellular calcium levels of PBMC were monitored using the calcium sensitive dye Fluo-3. Target cell populations were distinguished by forward scatter or following loading with the fluorescent dye, SNARF-1. Intracellular calcium was expressed as a ratio of fluorescence of conjugated to unconjugated PBMC and followed for ten minutes after initiation of conjugation. The results demonstrate an apparent increase in intracellular calcium in PBMC conjugated to the NK-sensitive cell line K562, and that the kinetics and magnitude of this response varied considerably between individuals. Tumour cells which were resistant to lysis (as determined in a 4 h chromium release assay) were also capable of eliciting a calcium response from PBMC. Although the induction of a rise in intracellular calcium was therefore not correlated with cytotoxicity, it was greater in IL-2-activated PBMC upon exposure to the same target cell lines as PBMC.

Aniline Compounds↗
PubMed1994

Changing causes of septicaemia in paediatric oncology patients: effect of imipenem use.

One hundred and fifty-four episodes of septicaemia occurred in 78 patients on a Paediatric Oncology Unit over 2 years. Septicaemias with Gram-positive bacteria were more common than with Gram-negative organisms, coagulase-negative staphylococci (CNS) being the commonest pathogens. The mortality rate in patients with septicaemia was 1.9%. Azlocillin and gentamicin comprised the first-line of empirical antibiotic therapy for suspected infection for the first 10 months of the study; imipenem with cilastatin, as monotherapy, was used subsequently. More isolates of enterococci, and fewer isolates of Enterobacter, were seen after the introduction of imipenem. The use of imipenem was associated with an increased frequency of resistance to flucloxacillin in CNS. Such strains have been shown to contain sub-populations of cells that are resistant to imipenem. A clinical response was achieved in 82.9% of septicaemic episodes treated with imipenem, compared with 62.7% for azlocillin and gentamicin. However, imipenem as monotherapy may not be appropriate in central venous catheter related infections, owing to the frequent occurrence of imipenem-resistant organisms, CNS and Pseudomonas spp., in this situation.

Bacteremia↗
PubMed1990

Transmembrane signaling during natural killer cell-mediated cytotoxicity. Regulation by protein kinase C activation.

NK cells can mediate either FcR-dependent cytotoxicity against antibody-coated target cells or direct cytotoxicity against a variety of tumor cells. We used homogeneous, cloned populations of CD16+/CD3- human NK cells to characterize and compare the transmembrane signaling mechanisms used during these alternative forms of cytotoxicity. Cross-linkage of NK cell FcR with anti-FcR (anti-CD16) mAb or direct binding to NK-sensitive tumor targets resulted in a rapid release of inositol phosphates and increases in [Ca2+]i. The receptor-dependent [Ca2+]i increase (as monitored in indo-1 loaded NK cells by flow cytometry) consisted of an initial release of calcium from intracellular stores, followed by a sustained influx of calcium across the plasma membrane. To assess the potential regulatory feedback role of protein kinase C (PKC) activation in these proximal signaling events, NK cells were pretreated with either PKC-activating phorbol esters, nonactivating phorbol ester homologs, or synthetic diacylglycerols. Brief pretreatment with activating phorbol esters rapidly inhibited, in a concentration-dependent manner, both phosphoinositide hydrolysis and increases in [Ca2+]i induced by FcR ligation, whereas pretreatment with an inactive phorbol ester had no effect. This acute inhibitory effect was not explained by FcR down-regulation, which occurred with more prolonged exposure to phorbol esters. In contrast, the phosphoinositide turnover and [Ca2+]i increase in NK cells stimulated with NK-sensitive tumor targets were not affected by prior exposure to PKC-activating phorbol esters. This differential regulatory effect of phorbol ester on proximal signaling was paralleled by a corresponding effect on cytotoxicity, i.e., phorbol ester-induced activation of PKC inhibited FcR-dependent cytotoxicity, but did not alter direct cytotoxicity against NK-sensitive tumor cells. These results indicate that PKC activation can differentially regulate alternative forms of NK cell-mediated cytotoxicity by rapidly and specifically desensitizing the FcR.

Antigens, Differentiation↗
PubMed1989

Steroid-responsive pure red cell aplasia associated with natural killer cell lymphocytosis.

A patient with pure red cell aplasia and expansion of the peripheral blood natural killer (NK) cell population is described. Despite normal absolute and differential leukocyte counts, NK cells were increased at diagnosis and at relapse. Furthermore, these cells were not morphologically recognizable on the peripheral blood smear examination. A favorable clinical response to glucocorticoid therapy was accompanied by a decrease in NK cells.

Azathioprine↗
PubMed1989

Acute megakaryocytic leukemia (M7) in children.

We analyzed the clinical and laboratory features of eight children (median age, 20 months; range, 13 months to 11 years) with acute megakaryocytic leukemia (M7) and compared the findings with those reported in the literature. The diagnosis was supported by ultrastructural examination for platelet peroxidase or immunophenotyping for glycoprotein IIb/IIIa or the von Willebrand factor protein. Two patients had Down's syndrome. Initial findings included anemia (in all patients), thrombocytopenia (in six), myelofibrosis (in three), lytic bone lesions (in two), and pronounced leukocytosis (in one). Stem cell culture studies of peripheral blood specimens revealed an aberrant phenotype of the megakaryocytes in one patient and reversal to a normal pattern after successful therapy. Remission was achieved in seven of the eight patients after aggressive chemotherapy, and four patients remained in remission 27 to 57 months after diagnosis. Three of these four patients underwent allogeneic bone marrow transplantation. M7 leukemia is not infrequent in children younger than 3 years of age, especially in those with Down's syndrome. The availability of monoclonal antibodies specific to restricted antigens of the megakaryocytic lineage has made the diagnosis of M7 leukemia both possible and practical.

Anemia↗
PubMed1988

Signal transduction during human natural killer cell activation: inositol phosphate generation and regulation by cyclic AMP.

NK cells mediate both direct cytotoxicity against a variety of tumor cells and indirect (FcR-dependent) cytotoxicity against antibody-coated targets. When cloned human NK cells (CD16+/CD3-) were exposed to NK-sensitive targets for 30 min, the level of inositol phosphates rose two to five times above background. The rise in inositol phosphates induced by NK-sensitive targets was paralleled by an increase in intracellular free calcium concentration ([Ca2+]i). A panel of tumor cells that were resistant to NK cell lysis did not stimulate significant levels of inositol phosphate production and did not induce an elevation of intracellular free calcium. Ligation of the FcR (CD16) with the mAb 3G8 also triggered phosphoinositide turnover. Kinetic experiments demonstrated that stimulation by either susceptible target cells or by FcR ligation led to rapid (less than 1 min) generation of the Ca2+-mobilizing second messenger, inositol trisphosphate, with slower accumulation of inositol bisphosphate and inositol monophosphate. Previous studies have demonstrated that activation of the cAMP-dependent second messenger pathway strongly inhibits NK cell-mediated cytotoxic functions. Treatment of NK effector cells with forskolin to elevate intracellular cAMP levels resulted in a concentration-dependent inhibition of phosphoinositide hydrolysis induced by both NK-sensitive targets and 3G8-mediated FcR ligation. These results suggest that phosphoinositide turnover represents a critical early event in the human NK cell cytolytic process. Moreover, the potent inhibitory effect of cAMP on NK cell cytotoxicity may be explained by the uncoupling of NK receptors from phospholipase C-mediated phosphoinositide hydrolysis.

Antibody-Dependent Cell Cytotoxicity↗