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Biomedical subjects

R Slater

Publications and source records attributed to R Slater.

At least 19 recordsLinked to original sources
PubMed2004

Patient communication during cataract surgery.

PURPOSE: Most cataract surgery is now performed under local anaesthesia on a day-case basis. As patients are fully conscious during the procedure, it is important that they remain still. There are a variety of reasons why patients may need to move, and it is important that the surgeon is made aware that this may happen. Some centres offer a nurse's hand as a means of perioperative patient communication. We sought to study the safety and efficacy of using an electronic patient-controlled alert device. METHOD: We compared hand-holding with the use of a patient alert device, and with both communication methods at the same time, on 150 subjects undergoing cataract surgery under local anaesthesia. Assessment of pre- and postoperative state anxiety was undertaken and patients' satisfaction with the communication strategies was assessed. RESULTS: There was a significant difference between pre- and postoperative state anxiety for each group (P<0.001) but no significant differences in pre-, peri-, or postoperative state anxiety between groups. There were no significant differences in confidence, pain, understanding, satisfaction, memory, and reassurance between the three groups. A total of 46% of all patients reported experiencing one or more of the potential problems enquired about, during the operation. Significant correlations were also identified between some of the psychological variables investigated. CONCLUSIONS: An electronic patient alert device is as effective a means of perioperative patient communication as holding a nurse's hand, during cataract surgery under local anaesthesia. It is safe, reassuring and it allows patients to communicate directly with the surgeon.

Aged↗
PubMed2004

Translocation t(2;3)(p15-23;q26-27) in myeloid malignancies: report of 21 new cases, clinical, cytogenetic and molecular genetic features.

Chromosomal rearrangements involving 3q26 either due to inversion or translocation with various partner chromosomes are a recurrent finding in malignant myeloid disorders. Typically, these chromosome aberrations contribute to ectopic expression of or to the formation of fusion genes involving the EVI1 proto-oncogene. Chromosomal translocations involving the short arm of chromosome 2 (p15-p23) and the distal part of the long arm of chromosome 3 (q26-q27) are a rare but recurrent finding in patients with myeloid malignancies, and are assumed to be part of this spectrum of disorders. Thus far, however, these translocations have been poorly studied. Here, we present 21 new cases with myelodysplasia, acute myeloid leukemia or CML in blast crisis, which upon karyotyping showed the presence of a t(2;3). Furthermore, an extensive literature review disclosed 29 additional cases. Morphological, clinical and cytogenetic assessment revealed the typical hallmarks of 3q26/EVI1 rearrangements, that is, trilineage dysplasia and dysmegakaryopoiesis, poor prognosis and additional monosomy 7. Molecular cytogenetic analysis and PCR in selected samples indicated that in most cases the translocation indeed targets the EVI1 locus. Mapping of the chromosome 2 breakpoints confirmed the initially suspected cytogenetic breakpoint heterogeneity at the 2p arm.

Acute Disease↗
PubMed2004

Detecting diminutive colorectal lesions at colonoscopy: a randomised controlled trial of pan-colonic versus targeted chromoscopy.

BACKGROUND: Diminutive and flat colorectal lesions can be difficult to detect using conventional colonoscopic techniques. Previous data have suggested that pan-chromoscopy may improve detection rates. No randomised control trial has been performed examining detection rates of such lesions while controlling for extubation time and lavage effect. AIM: We conducted a randomised controlled trial of pan-colonic chromoscopic colonoscopy for the detection of diminutive and flat colorectal lesions while controlling for extubation time and lavage effect. METHODS: Consecutive patients attending for routine colonoscopy were randomised to either pan-chromoscopy using 0.5% indigo carmine (IC) or targeted chromoscopy (control group). A minimum diagnostic extubation time was set at eight minutes with controls undergoing a matched volume of saline wash. RESULTS: A total of 260 patients were randomised; 132 controls and 128 to pan-colonic chromoscopy. Extubation times did not differ significantly between the control (median 15 minutes (range 8-41)) and chromoscopy (median 17 minutes (range 8-39)) groups. The volume of IC used in the pan-chromoscopy group (median 68 ml (range 65-90)) and normal saline used in the control group (69 ml (range 60-93)) did not differ significantly. There was a statistically significant difference between the groups regarding the total number of adenomas detected (p<0.05) with significantly more diminutive (<4 mm) adenomas detected in the pan-chromoscopy group (p = 0.03). Pan-chromoscopy diagnosed more diminutive and flat lesions in the right colon compared with controls (p<0.05), with more patients with multiple adenomas (>3) detected using pan-chromoscopy (p<0.01). Hyperplastic lesions were more commonly detected in the pan-chromoscopy group compared with controls (p<0.001). More hyperplastic polyps were detected in the left colon (86% rectosigmoid) using chromoscopy compared with controls. CONCLUSION: Chromoscopy improves the total number of adenomas detected and enhances the detection of diminutive and flat lesions. Importantly, eight diminutive lesions had foci of high grade dysplasia. Chromoscopy may benefit patients, assuming a high risk of colorectal cancer, and help in risk stratification and planning follow up colonoscopy intervals.

Adenoma↗
PubMed2002

BFM-oriented treatment for children with acute lymphoblastic leukemia without cranial irradiation and treatment reduction for standard risk patients: results of DCLSG protocol ALL-8 (1991-1996).

Modern treatment strategies, consisting of intensive chemotherapy and cranial irradiation, have remarkably improved the prognosis for children with acute lymphoblastic leukemia. However, patients with a potential for cure are at risk of severe acute and late adverse effects of treatment. Furthermore, in 25-30% of patients treatment still fails. The objectives of the DCLSG study ALL 8 were to decrease the toxicity and to increase the effectivity of BFM-oriented treatment. Decrease of toxicity was aimed at by confirmation of the results of the previous DCLSG study ALL-7, showing that the majority (94%) of children with ALL can successfully be treated with BFM-oriented therapy without cranial irradiation, and by reduction of treatment for standard risk (SRG) patients. To increase the cure rate in medium risk (MRG) patients the efficacy of high doses of intravenous 6-mercaptopurine (HD-6MP) during protocol M and in SRG patients the efficacy of high doses of L-asparaginase (HD-L-ASP) during maintenance treatment was studied in randomized studies. Patient stratification and treatment were identical to protocol ALL-BFM90, with the following differences: no prophylactic cranial irradiation, SRG patients received only phase 1 of protocol I. Four hundred and sixty-seven patients entered the protocol: 170 SRG, 241 MRG and 56 HRG patients. The 5 years event-free survival rate for all patients was 73% (s.e. 2%); for SRG, MRG and HRG patients 85% (s.e. 3%), 73% (s.e. 3%) and 39% (s.e. 7%), respectively. In patients >1 year of age at diagnosis unfavorable prognostic factors were male sex, >25% blasts in the bone marrow at day 15 and initial white blood cell count (WBC) >50 x 10(9)/l. The cumulative risk of CNS relapse rate was 5% (s.e. 1%) at 5 years. These results confirm that the omission of cranial irradiation in BFM-oriented treatment does not jeopardize the overall good treatment results, nor does early reduction of chemotherapy in SRG patients. No benefit was observed from treatment intensification with HD-L-ASP in SRG patients, nor from HD-6MP in MRG patients.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed2001

Fusion of the homeobox gene HLXB9 and the ETV6 gene in infant acute myeloid leukemias with the t(7;12)(q36;p13).

Recently, we and others reported a recurrent t(7;12)(q36;p13) found in myeloid malignancies in children < or =18 months of age and associated with a poor prognosis. Fluorescence in situ hybridization studies mapped the 12p13 breakpoint to the first intron of ETV6 and narrowed down the region of 7q36 involved. By using the sequences made public recently by the Human Genome Project, two candidate genes in 7q36 were identified: the homeobox gene HLXB9 and c7orf3, a gene with unknown function. Reverse transcription-PCR of two cases with t(7;12), using primers for c7orf3 and ETV6, was negative. However, reverse transcription-PCR for HLXB9-ETV6 demonstrated alternative splicing; the two major bands corresponded to fusion of exon 1 of HLXB9 to exons 2 and 3, respectively, of ETV6. The reciprocal ETV6-HLXB9 transcript was not detected. It remains to be elucidated if the leukemic phenotype is attributable to the formation of the HLXB9-ETV6 fusion protein, which includes the helix-loop-helix and E26 transformation-specific DNA binding domains of ETV6 or to the disruption of the normal ETV6 protein.

Acute Disease↗
PubMed2001

DMBA-induced toxic and mutagenic responses vary dramatically between NER-deficient Xpa, Xpc and Csb mice.

Heterogeneity in cancer susceptibility exists between patients with an inherited defect in nucleotide excision repair (NER). While xeroderma pigmentosum (XP) patients have elevated skin cancer rates, Cockayne syndrome (CS) patients do not appear to have increased cancer susceptibility. To investigate whether differences in mutagenesis are the basis for the variability in cancer proneness, we studied mutagenesis at the X-chromosomal Hprt gene and the autosomal Aprt gene in splenic T-lymphocytes after 7,12-dimethyl-1,2-benz[a]anthracene (DMBA) exposure in total NER-deficient Xpa mice, global genome repair (GGR)-deficient Xpc mice and transcription coupled repair (TCR)-deficient Csb mice. Surprisingly, while all intraperitoneally-treated Xpc(-/-) mice survived a dose of 40 mg/kg DMBA, a substantial fraction of the treated Xpa(-/-) and Csb(-/-) mice died a few days after treatment with a 20-fold lower dose. Functional TCR of DMBA adducts in Xpc(-/-) mice thus appears to alleviate DMBA toxicity. However, the mutagenic response in Xpc(-/-) mice was +/- 2-fold enhanced at both the Hprt and the Aprt gene compared to heterozygous controls, indicating that GGR at least partially removes DMBA adducts from the genome overall. DMBA-induced SCE frequencies in mouse dermal fibroblasts were significantly enhanced in Xpa- and Csb-, but not in Xpc-deficient background compared to the frequency in normal fibroblasts. These results indicate that both damage-induced cytotoxicity as well as intra-chromosomal recombinational events were not correlated to differences in cancer susceptibility in human NER syndrome patients.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed2001

Molecular cytogenetic and clinical findings in ETV6/ABL1-positive leukemia.

Rearrangements of 12p, resulting from deletions or translocations, are common findings in hematologic malignancies. In many cases, these rearrangements target the ETV6 gene (previously called TEL) located at 12p13. Various partner genes have been implicated in the formation of fusion genes with ETV6. These include PDGFRB, JAK2, NTRK3, ABL2, and ABL1, each of which encodes for proteins with tyrosine kinase activity. To date, ETV6/ABL1 transcripts have been detected in only four patients with a leukemic disorder. Here, we describe one adult with chronic myeloid leukemia and a child with T-cell acute lymphocytic leukemia with ETV6/ABL1. Molecular cytogenetic analysis confirmed that formation of an ETV6/ABL1 fusion in these patients required at least three chromosomal breaks and showed that each of these translocations is the result of a complex chromosomal rearrangement. Molecular analysis showed the presence of two fusion transcripts in both patients as the result of alternative splicing, questioning the suggested role of these transcripts in the lineage specificity. Clinical findings of these patients were compared to those of previously reported cases, and the possible clinical and biological similarities between ETV6/ABL1 and other fusion genes leading to increased tyrosine kinase activity are discussed.

Child, Preschool↗
PubMed2000

Characterization of mRAD18Sc, a mouse homolog of the yeast postreplication repair gene RAD18.

The RAD18 gene of the yeast Saccharomyces cerevisiae encodes a protein with ssDNA binding activity that interacts with the ubiquitin-conjugating enzyme RAD6 and plays an important role in postreplication repair. We identified and characterized the putative mouse homolog of RAD18, designated mRAD18Sc. The mRAD18Sc open reading frame encodes a 509-amino-acid polypeptide that is strongly conserved in size and sequence between yeast and mammals, with specific conservation of the RING-zinc-finger and the classic zinc-finger domain. The degree of sequence conservation between mRAD18Sc, RAD18, and homologous sequences identified in other species (NuvA from Aspergillus nidulans and Uvs-2 from Neurospora crassa) is entirely consistent with the evolutionary relationship of these organisms, strongly arguing that these genes are one another's homologs. Consistent with the presence of a nuclear translocation signal in the amino acid sequence, we observed the nuclear localization of GFP-tagged mRAD18Sc after stable transfection to HeLa cells. mRNA expression of mRAD18Sc in the mouse was observed in thymus, spleen, brain, and ovary, but was most pronounced in testis, with the highest level of expression in pachytene-stage primary spermatocytes, suggesting that mRAD18Sc plays a role in meiosis of spermatogenesis. Finally, we mapped the mRAD18Sc gene on mouse chromosome 6F.

Amino Acid Sequence↗
PubMed2000

Long-term follow-up of Dutch Childhood Leukemia Study Group (DCLSG) protocols for children with acute lymphoblastic leukemia, 1984-1991.

Here we report the long-term results of the DCLSG protocols ALL-6 and -7 with special emphasis on the incidence of CNS relapse after treatment without cranial irradiation. In DCLSG protocol ALL-6 (1984-1988), designed for patients with ALL non-high risk (ALL-NHR) (WBC <50 x 10(9)/l, no mediastinal mass, no B cell phenotype and no CNS involvement at diagnosis, comprising 71% of all ALL patients), CNS prophylaxis consisted of a combination of three methods of chemotherapeutic CNS prophylaxis (the use of dexamethasone during induction and maintenance therapy, i.v. medium dose methotrexate and prolonged administration of intrathecal triple therapy). Total duration of treatment: 116 weeks. 190 patients were enrolled in the study. At 10 years, the EFS rate for all patients is 81.5 +/- 2.8%, the survival rate 84.8 +/- 2.7%, and the cumulative incidence of isolated CNS relapse 1.1 +/- 0.8%. The 10-year survival rate for the 139/190 (73.1%) patients with standard risk non-T lineage ALL according to the NCI risk criteria is 80.5 +/- 3.4%. DCLSG protocol-7 was identical to the intensive ALL-BFM-86 protocol, but cranial irradiation was restricted to patients with initial CNS involvement. Patients were stratified into three risk groups (SRG, RG and EG). Treatment duration was 18 months. 218 patients were enrolled in the study. At 10 years, the EFS rate for all patients is 63.4 +/- 3.3%, the survival rate 76.4 +/- 3.0%, the 5-year cumulative incidence of isolated CNS relapse 5.7 +/- 1.8%. The EFS rate at 10 years of the 127/218 (58.3%) patients with standard risk non-T-lineage ALL according to the NCI risk criteria was 67.9 +/- 4.3%, which is not significantly different from the results achieved in this category of patients with the moderately intensive treatment according to protocol ALL-6 (logrank P = 0.17). These DCLSG studies indicate that omission of cranial irradiation does not jeopardize the overall good results.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed2000

Effectiveness of the particle repositioning maneuver in subtypes of benign paroxysmal positional vertigo.

OBJECTIVES: To assess the efficacy of the particle repositioning maneuver (PRM) in patients presenting with idiopathic benign paroxysmal positional vertigo (BPPV) compared with those with evidence of additional peripheral vestibulopathies. METHODS: Retrospective administration of the Dizziness Handicap Inventory (DHI) to 41 patients with primary BPPV and 31 patients with secondary BPPV to subjectively evaluate their symptoms before and after the PRM. RESULTS: Both groups indicated a marked improvement in symptoms after the PRM. Only two patients reported an increase in their symptoms after the PRM and both had secondary BPPV. CONCLUSIONS: The PRM was found to be highly effective in all forms of BPPV, but careful history and judicious testing may identify patients requiring additional intervention to relieve their symptoms.

Adult↗
PubMed1999

Intensive treatment of children with acute lymphoblastic leukemia according to ALL-BFM-86 without cranial radiotherapy: results of Dutch Childhood Leukemia Study Group Protocol ALL-7 (1988-1991).

In The Netherlands from July 1988 to October 1991, children (0 to 16 years of age) with de novo acute lymphoblastic leukemia (ALL) were treated according to protocol ALL-7 of the Dutch Childhood Leukemia Study Group (DCLSG). In this protocol, chemotherapy and treatment stratification were identical to the ALL-BFM-86 protocol (Reiter et al, Blood 84:3122, 1994), but cranial irradiation was restricted to patients with initial central nervous system (CNS) involvement. Patients were stratified into 3 risk groups, based on leukemia cell mass and response to initial treatment: standard-risk group (SRG), risk group (RG), and experimental group (EG). As in ALL-BFM-86, a randomized study on late intensification (protocol S) was performed in RG patients, and during the study (since October 1990), early reinduction treatment (protocol II) was introduced for SRG patients. Treatment duration for all patients was 18 months. Two hundred eighteen children entered the study: 74 SRG, 127 RG, and 17 EG patients. The overall complete remission (CR) rate was 98%. The 5-year event-free survival (EFS) for all DCLSG ALL-7 patients was 65. 3% (standard error [SE] 3.2%), which was significantly different from the 73% (SE 1%) 5-year EFS achieved in the ALL-BFM-86 study (P =.02, Z-test). However, restricting the analysis to SRG patients receiving protocol II with a total duration of treatment of 18 months, the 5-year EFS rates were 64.6% (SE 4.0%) and 67% (SE 4%), respectively, and no significant difference could be established (P =.67, Z-test). The 5-year EFS rates for SRG, RG, and EG patients were 63.5% (SE 5.6%), 66.6% (SE 4.2%), and 63.3% (SE 12.0%), respectively. SRG patients receiving protocol II fared better than patients not receiving protocol II (5-year EFS 76.7% [SE 7.7] and 54. 5% [SE 7.5], respectively). No difference in 5-year EFS was observed in RG patients randomized to receive or not to receive late intensification with protocol S. The overall CNS relapse rate at 5 years was 5.5%. The incidence rate at 5 years was 11.4% in SRG patients not receiving protocol II, whereas no CNS relapses occurred in SRG patients receiving protocol II. Six children died in first complete remission and 2 children developed a second malignancy (thyroid carcinoma and acute nonlymphoblastic leukemia). Systemic high-dose methotrexate (MTX) and intrathecal chemotherapy is a safe and effective method of CNS prophylaxis in the context of BFM-oriented treatment for all children with ALL, regardless of the risk group (with the possible exception of T-ALL patients with high white blood cell counts). The results of the DCLSG ALL-7 study confirm those of the ALL-BFM-86 study showing that early reinduction with protocol II is essential in the treatment of SRG patients and that late intensification with protocol S does not improve the prognosis for RG patients.

Adolescent↗
PubMed1999

Promoter transgenics reveal multiple gonadotropin-releasing hormone-I-expressing cell populations of different embryological origin in mouse brain.

Gonadotropin-releasing hormone-I (GnRH-I) is thought to be expressed by a single, highly spatially restricted group of neurons, which originate in the olfactory placode and migrate through the nose into the medial septum and hypothalamus from where they control fertility. Transgenic mice bearing a 13.5 kb GnRH-I-lacZ reporter construct were derived and found to express high levels of beta-galactosidase mRNA and protein within the septohypothalamic GnRH neurons in a correct temporal and spatial manner. Unexpectedly, low levels of beta-galactosidase were also present in three further populations of cells within the lateral septum, bed nucleus of the stria terminalis, and tectum. Analysis of wild-type mice with three different GnRH-I antibodies revealed distinct and transient patterns of GnRH-I peptide expression during development in all three of these populations revealed by transgenics. The synthesis of GnRH by cells of the lateral septum was the most persistent and remained until the third postnatal week. Embryonic "small eye" Pax-6 null mice, which fail to develop an olfactory placode, were also examined and shown to have equivalent populations of GnRH-I-immunoreactive cells in the lateral septum, tectum, and bed nucleus of the stria terminalis but none of the migrating cells that form the septohypothalamic GnRH population. These results prove that so-called "ectopic" expression in promoter transgenic lines can reflect authentic developmental patterns of gene expression. They further provide the first demonstration in mammalian brain that multiple neuronal populations of different embryological origin express GnRH-I peptide during embryonic and postnatal development.

Animals↗