The importance of identity and empowerment to teenagers with developmental co-ordination disorder.

AIMS: The aim of the current study was to gain an understanding of the experiences and aspirations of young people living with Developmental Coordination Disorder (DCD) in their own words. METHODS: Eleven young people aged 11-16 years with a prior diagnosis of DCD were identified from child health records of two participating NHS trusts. The sample included seven boys and four girls, from different socio-economic backgrounds living in different parts of one large urban area in England. In depth one-to-one semi-structured interviews and subsequent follow-up small group interviews were carried out with the young people. Interviews were enhanced using participatory arts-based techniques. All interviews were recorded verbatim and transcribed. Narrative data were analysed using Lindseth's interpretive phenomenology. RESULTS: The central theme of 'We're all different' described how the young person saw themselves and encompassed the formation of identity. Subthemes illustrated the attitude of the young people to their day to day lives, their difficulties and strategies used by the young people to overcome these difficulties in school and at home. The attitude of the school to difference, the presence of bullying, the accepting nature of the class, teachers and peers were vitally important. Areas of life that encouraged a positive sense of identity and worth included being part of a social network that gave the young people a sense of belonging, potentially one that valued differences as well as similarities. CONCLUSION: The current work highlights the need for services to adopt a model of DCD where the young person talks about what they can do and considers strategies of overcoming their difficulties. This has implications for education and future intervention strategies that focus on fostering psychological resilience and educational coping strategies rather than simply attempting to improve motor skills.

Dominantly inherited beta thalassaemia intermedia caused by a new single nucleotide deletion in exon 2 of the beta globin gene: Hb morgantown (beta91 CTG>CG).

Family members in multiple generations of an Irish-American family were investigated for moderate to severe microcytic anaemia, inherited in an autosomal dominant fashion. A novel frameshift mutation of the beta globin gene was discovered. This study highlights the importance of considering dominantly inherited beta thalassemia in the investigation of anaemia, even in patients with ethnic backgrounds not usually associated with beta thalassaemia.

Late-developing Philadelphia chromosomes in a case of T-cell acute lymphoblastic leukemia.

A child with T-cell acute lymphoblastic leukemia (ALL) is presented who at relapse acquired two Philadelphia chromosomes (Ph). Molecular studies at relapse revealed a rearrangement of the major breakpoint cluster region (M-bcr) on chromosome 22. No rearrangements of the immunoglobulin heavy chain or T-cell beta receptor gene loci were demonstrated. This case supports the hypothesis that leukemogenesis in Ph-positive malignancies is a multi-step process, the first step of which may not necessarily involve acquisition of the Ph.

Methylation status of the major breakpoint cluster region in Philadelphia chromosome negative leukemias.

It has been shown that a 600 bp long cluster of cell lineage specific hypomethylated sites in the major breakpoint cluster region (M-bcr) on chromosome 22 exists in hematopoietic cells. To determine possible relationships between methylation patterns within the M-bcr and the stage of hematopoietic cell development, the M-bcr methylation status of 39 patients with leukemia and lymphoma and two patients with myelodysplastic syndrome with non-rearranged M-bcrs was examined by BgIII-HpaII digestion. In the myeloid malignancies, the presence of a hypermethylated 4.8 kb BgIII-BgIII M-bcr allele was directly proportional to the combined myeloblast and promyelocyte percentage of the specimen, whereas the presence of a 2.5 kb BgIII-HpaII allele was directly proportional to the combined percentage of monocytic cells and neutrophils. All five acute monoblastic leukemias showed a methylation pattern that closely resembled neutrophils. All of thirteen surface immunoglobulin positive B-cell malignancies showed a distinct methylation pattern consisting of three or more BgIII-HpaII restriction fragments of 2.5 kb or less in length. The B-cell precursor leukemias showed heterogeneous M-bcr methylation patterns, with four of seven showing a B-cell pattern and three showing a hypermethylated pattern with 4.8, 3.1/3.0 and/or 2.5 kb BgIII-HpaII M-bcr alleles. It is concluded that the M-bcr methylation status is related to the maturation of the neutrophil series; the surface immunoglobulin positive B-cell malignancies are characterized by a distinct, extreme hypomethylation pattern of the M-bcr; and the B-cell precursor malignancies appear to have a heterogeneous M-bcr methylation pattern.

Transformation of chronic lymphocytic leukemia to small non-cleaved cell lymphoma: a cytogenetic, immunological, and molecular study.

A patient with chronic lymphocytic leukemia (CLL) transforming into a small non-cleaved cell lymphoma (SNCL) with the occurrence of a t(8;22) is described. The SNCL and the CLL were both found to have a germline lambda light chain gene configuration and the same heavy chain and kappa light chain gene rearrangements. The SNCL was CD10 (CALLA) negative and appeared to be CD5 negative. It is concluded that the SNCL is derived from the CLL and that activation of the c-myc oncogene may have played a role in this transformation.

Correlation of PCR-detected clonal gene rearrangements with bone marrow morphology in patients with B-lineage lymphomas.

Bone marrow biopsy is the conventional staging and posttherapy evaluation method for assessing marrow involvement by lymphoma. Polymerase chain reactions (PCR) for antigen receptor rearrangements have the potential to increase the detection of minimal degrees of marrow involvement. The present study is a concurrent morphologic and PCR evaluation of 225 staging or posttherapy marrow biopsies from 127 patients with B-lineage non-Hodgkin's lymphoma. The biopsies were morphologically categorized into four groups: group 1 (positive for lymphoma), 60 biopsies (27%); group 2 (suspicious for lymphoma), 20 biopsies (9%); group 3 (lymphocytic lesions of indeterminate biology), 22 biopsies (10%); and group 4 (negative for lymphoma), 123 biopsies (54%). Molecular studies were performed on concurrently obtained aspirates and used consensus immunoglobulin-heavy-chain (IgH) and IgH/bcl-2 gene PCR primers. A molecular clone was detected in 53 of the 225 aspirates (24%): group 1, 34 aspirates (57%); group 2, five aspirates (25%); group 3, one aspirate (5%); and group 4, 13 aspirates (11%). A PCR-positive aspirate was present in 47% of follicular lymphomas, 58% of diffuse large cell lymphomas, and 72% of the other lymphomas in the group I specimens. Morphology or PCR was positive in 79 of the 225 cases (35%). The molecular detection of clonality in the aspirate DNA from cases with positive morphologic findings was lower than anticipated. The discordance between morphology and PCR results may be related to sample variation between the trephine biopsy and aspirate, a failure to aspirate sufficient lymphoma cells, or insufficient primer homology for amplification. DNA extracted from trephine sections may provide results more concordant with morphology, because PCR detected a clone in 10 of 11 DNA specimens extracted from trephine biopsies with positive morphologic findings and PCR negative aspirates.

Microcephaly with agenesis of corticospinal tracts and arthrogryposis, hypospadias, single umbilical artery, hypertelorism, and renal and adrenal hypoplasia--previously undescribed syndrome.

We describe a small, term, male infant with corticospinal tract aplasia secondary to motor cortex dysplasia from a neuronal proliferation and/or migrational defect. The infant also had microdolichocephaly, sloping forehead, hypertelorism, flat nose, apparently low-set ears, micrognathia, arthrogryposis without muscle wasting, cortical thumbs, rocker-bottom feet, scoliosis, single umbilical artery, and hypospadias with chordee. Oligohydramnios was present prenatally. Neurologic examination showed a comatose state, seizures, minimal spontaneous movement, minimal response to pain, and absent primitive reflexes. At autopsy, hypoplasia of kidneys and adrenal glands was found. There was no aqueductal stenosis or pulmonary hypoplasia. Chromosomes were apparently normal. These manifestations do not correspond to those of any recognized syndrome; therefore, this patient may represent a previously undefined syndrome.

Perinodular hydropic degeneration of a uterine leiomyoma: a diagnostic challenge.

Perinodular hydropic degeneration of a uterine leiomyoma is a rare form of the more common hydropic change observed in leiomyomas. With minimal discussion in the surgical pathology literature, appropriate evaluation may be challenging because the differential diagnosis includes other uncommon uterine disorders such as intravenous leiomyomatosis, diffuse leiomyomatosis, myxoid leiomyosarcoma, endometrial stromal sarcoma, angiofibroma, and angiomyxoma. We describe such a diagnostic challenge in a 42-year-old woman with a left adnexal mass discovered during an annual examination. With only three cases of perinodular hydropic degeneration previously reported, this case is the first with extrauterine extension and was initially concerning for a more aggressive process.

Splenectomy in lymphoproliferative disorders: a report on 70 cases and review of the literature.

Between February, 1970 and September, 1991, we performed splenectomies on 70 patients with chronic lymphoproliferative disorders including primary leukemias: 19 B-cell chronic lymphocytic leukemia, 1 B-cell prolymphocytic leukemia, 22 hairy cell leukemias, 4 large granular lymphocytic leukemias, 1 T-cell prolymphocytic leukemia, and non-Hodgkin's lymphomas (NHL): 10 splenic lymphomas with villous lymphocytes, 4 follicular lymphomas, 5 mantle cell lymphomas, 3 lymphoplasmacytic and 1 large cell NHL. The primary indications for surgery in this series were therapy-resistant disease (40%) and therapeutic splenectomy (38%). Postsplenectomy, 70% of patients had a complete hematological response, 23% had a partial response, and 7% were nonresponsive. Median treatment-free survival correlated with the hematologic response postsplenectomy and the underlying diagnosis. Better treatment-free survivals were seen in patients with lesser degrees of anemia and thrombocytopenia. Overall, improvements were more pronounced in the B-cell than in the T-cell disorders. Indications for further therapy, postoperative morbidity and mortality, and survival times are discussed along with a review of the literature. These findings advocate a continuing role for splenectomy in symptomatic lymphoid malignancies running with splenomegaly and hypersplenism.

Familial hemifacial spasm associated with arterial compression of the facial nerve. Case report.

This report of an 88-year-old woman with familial hemifacial spasm includes the first published postmortem description of hemifacial spasm with cross-compression of the seventh cranial nerve root exit zone by a redundant loop of the anterior inferior cerebellar artery and associated vascular plexus. Histological examination of the seventh and eighth cranial nerve complex suggested nerve degeneration because increased numbers of corpora amylacea were present just distal to the compression concavity. There was no evidence of demyelination or gliosis of the nerve. This case suggests that vascular compression of the nerve root exit zone is an important condition in the etiology of most of these cases. This is the third reported case of familial hemifacial spasm; to date, all such patients have had left facial involvement. The family pedigree in this case suggests a pattern of autosomal-dominant inheritance with partial penetrance. The genetic basis for familial hemifacial spasm may involve anatomical variants or anomalies of the posterior circulation, since both posterior inferior cerebellar arteries were congenitally absent in this case.

Evaluation of thermal therapy in a prostate cancer model using a wet electrode radiofrequency probe.

PURPOSE: To determine the temperature-time threshold of local cell death in vivo for thermal therapy in a prostate cancer animal model and to use this value as a benchmark to quantify global tissue injury. MATERIALS AND METHODS: Two studies were designed in the Dunning AT-1 rat prostate tumor hind limb model. For both studies, a wet electrode radiofrequency (RF) probe was used to deliver 40 W of energy for 18 to 62 seconds after a 30-second infusion of hypertonic saline/Hypaque through the RF antenna. Thermal history measurements were obtained in tumors from at least two Fluoroptic probes placed radially 5 mm from the axis of a RF probe and 10 mm below the surface of the tissue. In study 1, the thermal history required for irreversible cell injury was experimentally determined by comparing the predicted injury accumulation (omega) with cell viability at the fluoroptic probe locations using an in vivo-in vitro assay. The omega value was calculated from the measured thermal histories using an Arrhenius damage model. In study 2, RF energy was applied for 40 seconds in all cases. At 1, 3, and 7 days after thermal therapy, triphenyltetrazolium chloride dye (TTC) and histologic analyses were performed to assess global tissue injury within a 5-mm radius from the axis of the RF probe. RESULTS: Study 1 showed that cell survival dropped to 0 for 0.42 < omega < 0.7. This result was the basis for selection of 40 seconds of RF thermal therapy in study 2, which yielded omegaave = 0.5 in the tissue 5 mm from the probe axis. Both TTC and histology analysis showed that sham-treated tissue was not irreversibly injured. However, there was an inherent heterogeneity present in the tumor that accounted for as much as 15% necrosis in control or sham-treated tissue. In contrast, at 1, 3, and 7 days after therapy, significantly less enzyme activity was observed by TCC in thermally treated tissue compared with sham-treated tissue (35 v 85%; P < 0.001). Histologic analysis of thermally treated tissues revealed a gradual increase in the percent of coagulative necrosis (47%-70%) with a concomitant decrease in the percentage of shocked cells (53%-28%). At day 7, <3% viability was observed in treated tumors compared with 90% viability in sham-treated tissue. CONCLUSION: The threshold of cellular injury in vivo corresponded to omega > 0.7 (> or =48 degrees C for 40 seconds). Global tissue injury could be conservatively predicted on the basis of local thermal histories during therapy.

Measurement and prediction of thermal behavior and acute assessment of injury in a pig model of renal cryosurgery.

PURPOSE: To analyze in vivo end temperatures and histologic injury in a standardized cryo-iceball using a porcine kidney model in order to establish the threshold temperature for tissue ablation. To evaluate the ability to predict end temperatures using a thermal finite element model. MATERIALS AND METHODS: A single freeze/thaw cryolesion was created in five pig kidneys and the temperature history recorded. End temperature was calculated using a thermal finite element model. The threshold temperature for tissue injury was established by directly correlating end temperature and histologic injury. RESULTS: Reproducible geometry and temperature profiles of the cryo-iceball were found. End temperature could be accurately predicted through thermal modeling, and correlation with histologic injury revealed a threshold temperature of -16.1 degrees C for complete tissue ablation. CONCLUSION: Thermal modeling may accurately predict end temperature within a cryo-iceball. Provided threshold temperatures for tissue destruction are known, modeling may become a powerful tool in cryosurgery, improving the assessment of damage in normal and malignant tissue.

Antitumor effect of beta-elemene in non-small-cell lung cancer cells is mediated via induction of cell cycle arrest and apoptotic cell death.

Beta-elemene is a novel anticancer drug, which was extracted from the ginger plant. However, the mechanism of action of beta-elemene in non-small-cell lung cancer (NSCLC) remains unknown. Here we show that beta-elemene had differential inhibitory effects on cell growth between NSCLC cell lines and lung fibroblast and bronchial epithelial cell lines. In addition, beta-elemene was found to arrest NSCLC cells at G2-M phase, the arrest being accompanied by decreases in the levels of cyclin B1 and phospho-Cdc2 (Thr-161) and increases in the levels of p27(kip1) and phospho-Cdc2 (Tyr-15). Moreover, beta-elemene reduced the expression of Cdc25C, which dephosphorylates/activates Cdc2, but enhanced the expression of the checkpoint kinase, Chk2, which phosphorylates/ inactivates Cdc25C. These findings suggest that the effect of beta-elemene on G2-M arrest in NSCLC cells is mediated partly by a Chk2-dependent mechanism. We also demonstrate that beta-elemene triggered apoptosis in NSCLC cells. Our results clearly show that beta-elemene induced caspase-3, -7 and -9 activities, decreased Bcl-2 expression, caused cytochrome c release and increased the levels of cleaved caspase-9 and poly(ADP-ribose) polymerase in NSCLC cells. These data indicate that the effect of beta-elemene on lung cancer cell death may be through a mitochondrial release of the cytochrome c-mediated apoptotic pathway.

Microscopic and calorimetric assessment of freezing processes in uterine fibroid tumor tissue.

The use of cryosurgery in the treatment of uterine fibroids is emerging as a possible treatment modality. The two known mechanisms of direct cell injury during the tissue freezing process are linked to intracellular ice formation and cellular dehydration. These processes have not been quantified within uterine fibroid tumor tissue. This study reports the use of a combination of freeze-substitution microscopy and differential scanning calorimetry (DSC) to quantify freeze-induced dehydration within uterine fibroid tumor tissue. Stereological analysis of histological tumor sections was used to obtain the initial cellular volume (V(o)) or the Krogh model dimensions (deltaX, the distance between the microvascular channels = 15.5 microm, r(vo), the initial radius of the extracellular space = 4.8 micro m, and L, the axial length of the Krogh cylinder = 19.1 microm), the interstitial volume ( approximately 23%), and the vascular volume ( approximately 7%) of the fibroid tumor tissue. A Boyle-van't Hoff plot was then constructed by examining freeze-substituted micrographs of "equilibrium"-cooled tissue slices to obtain the osmotically inactive cell volume, V(b) = 0.47V(o). The high interstitial volume precludes the use of freeze-substitution microscopy data to quantify freeze-induced dehydration. Therefore, a DSC technique, which does not suffer from this artifact, was used to obtain the water transport data. A model of water transport was fit to the calorimetric data at 5 and 20 degrees C/min to obtain the "combined best fit" membrane permeability parameters of the embedded fibroid tumor cells, assuming either a Krogh cylinder geometry, L(pg) = 0.92 x 10(-13) m(3)/Ns (0.55 microm/min atm) and E(Lp) = 129.3 kJ/mol (30.9 kcal/mol), or a spherical cell geometry (cell diameter = 18.3 microm), L(pg) = 0.45 x 10(-13) m(3)/Ns (0.27 microm/min atm) and E(Lp) = 110.5 kJ/mol (26.4 kcal/mol). In addition, numerical simulations were performed to generate conservative estimates, in the absence of ice nucleation between -5 and -30 degrees C, of intracellular ice volume in the tumor tissue at various cooling rates typical of those experienced during cryosurgery (< or =100 degrees C/min). With this assumption, the Krogh model simulations showed that the fibroid tumor tissue cells cooled at rates < or = 50 degrees C/min are essentially dehydrated; however, at rates >50 degrees C/min the amount of water trapped within the tissue cells increases rapidly with increasing cooling rate, suggesting the formation of intracellular ice.