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S Richards

Publications and source records attributed to S Richards.

At least 55 records · Page 3Linked to original sources
PubMed2000

Monosomy 20 as a pointer to dicentric (9;20) in acute lymphoblastic leukemia.

Twenty new cases of acute lymphoblastic leukemia (ALL) with the dicentric chromosome dic(9;20)(p1113;q11) are presented. This chromosomal abnormality is difficult to identify from G-banding alone. It masquerades as monosomy 20 and is only accurately identified by fluorescence in situ hybridization (FISH). Monosomy 20 was found in 59/2790 patients with successful karyotypes entered to the Leukaemia Research Fund/UK Cancer Cytogenetics Group Karyotype Database in ALL (LRF/UKCCG Karyotype Database). FISH revealed dic(9;20) in 20/25 cases with available material. Extra copies of chromosome 21 were found in 8 of the 20 cases. Patients were 14 females and six males, aged 1-32 years (median 4 years), with leukocyte counts of 2-536 (median 23) x 109/l and immunophenotypes of common or pre-B ALL (17 cases), T-ALL (one case) or unknown (two cases). Four patients relapsed at 2, 22, 28 and 47 months and two died at 49 and 63 months (median follow-up 37 months). FISH studies on the remaining five patients showed one with monosomy 20 and four with other rearrangements of the chromosome. This study has increased the number of reported cases of dic(9;20) from 17 to 37. It has identified dic(9;20) in one case of T-ALL and shows an association of this translocation with trisomy 21.

Adolescent↗
PubMed2000

Benefit of intensified treatment for all children with acute lymphoblastic leukaemia: results from MRC UKALL XI and MRC ALL97 randomised trials. UK Medical Research Council's Working Party on Childhood Leukaemia.

Treatment of children with acute lymphoblastic leukaemia (ALL) aims to cure all patients with as little toxicity as possible and, if possible, to restrict further intensification of chemotherapy to patients with an increased risk of relapse. However in Medical Research Council (MRC) trial UKALL X two short myeloablative blocks of intensification therapy given at weeks 5 and 20 were of benefit to children in all risk groups. The successor trials, MRC UKALL XI and MRC ALL97, tested whether further intensification would continue to benefit all patients by randomising them to receive, or not, an extended third intensification block at week 35. After a median follow-up of 4 years (range 5 months to 8 years), 5 year projected event-free survival was superior at 68% for the 894 patients allocated a third intensification compared with 60% for the 887 patients who did not receive one (odds ratio 0.75, 95% CI 0.63-0.90, 2P = 0.002). This difference was almost entirely due to a reduced incidence of bone marrow relapses in the third intensification arm (140 of 891 in the third intensification arm vs. 171 of 883 in the no third intensification, 2P = 0.02). Subgroup analysis suggests benefit of the third intensification for all risk categories. Overall survival to date is no different in the two arms, indicating that a greater proportion of those not receiving a third intensification arm and subsequently relapsing can be salvaged. These results indicate that there is benefit of additional intensification for all risk subgroups of childhood ALL.

Adolescent↗
PubMed2000

Long-term follow-up of the United Kingdom Medical Research Council protocols for childhood acute lymphoblastic leukaemia, 1980-1997. Medical Research Council Childhood Leukaemia Working Party.

Results of three consecutive completed UK trials (1980-1997) for childhood lymphoblastic leukaemia are presented. National accrual has progressively increased so that over 90% of all the country's ALL cases were treated on the latest trial reported, UKALLXI. From 1980 to 1990, event-free and overall survival progressively improved, following adoption of an American therapy template and use of two post-remission intensification modules. Since 1990 despite demonstration of the benefit of a third intensification module overall event-free survival (EFS) has not improved further. Survival remains high due to a good retrieval rate especially for those relapsing off treatment after receipt of two intensification pulses. Possible reasons for the plateau in event-free survival (including type and dose of induction steroid, dropping of induction anthracycline, type and dose of asparaginase, gaps early in therapy following intensification, and overall lack of compliance in maintenance) are being explored in the latest protocol ALL '97. Cranial irradiation had been successfully replaced by a long course of intrathecal methotrexate injections for the majority of patients. Age (<1 year >10 years) sex (male) and white count >50 x 10(9)/l plus slow initial bone marrow clearance were consistently the most important independent prognostic indicators during this time period. Rome/NCI criteria accurately predict standard and high-risk groups for B cell lineage, but not consistently for T cell disease. This international collaborative venture might help us to define those truly at highest risk, and how we can optimise therapy for specific subgroups including T-ALL and those with unfavourable cytogenetics.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed2000

The UK experience in treating relapsed childhood acute lymphoblastic leukaemia: a report on the medical research council UKALLR1 study.

We have examined the toxicity and overall outcome of the Medical Research Council UKALL R1 protocol for 256 patients with relapsed childhood acute lymphoblastic leukaemia (ALL). Second remission was achieved in over 95% of patients. Two patients died during induction and seven patients died of resistant disease. The overall actuarial event-free survival (EFS) at 5 years for all patients experiencing a first relapse was 46% (95% CI 40-52). Duration of first remission, site of relapse, age at diagnosis and sex emerged as factors of prognostic significance. Five-year EFS was only 7% for children relapsing in the bone marrow within 2 years of diagnosis, but was 77% for those relapsing without bone marrow involvement > 2.5 years from diagnosis. All analyses in this report are by treatment received. For those receiving chemotherapy alone, the 5-year EFS was 48%; for autologous bone marrow transplantation (BMT), the 5-year EFS was 47%; for unrelated donor BMT, it was 52%; and for related donor BMT, the 5-year EFS was 45%. The groups, however, were not comparable with respect to risk factor profile, and therefore direct comparison of EFS is misleading. Adjustment for time to transplant and prognostic factors was used to reduce the effects of biases between treatment groups, but did not suggest benefit for any particular treatment. There was failure of our planned randomization scheme in this trial with only 9% of those eligible being randomized, which highlights the difficulties in running randomized trials especially in patients who have relapsed from a previous trial. The optimal treatment for relapsed ALL therefore remains uncertain. Alternative approaches are clearly needed for those with early bone marrow relapse if outcome is to improve.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed2000

Standardization of lymphocyte antibody binding capacity - a multi-centre study.

As quantitative flow cytometry is being increasingly used to characterize non-malignant and malignant disorders, interlaboratory standardization becomes an important issue. However, the lack of standardized methods and process controls with predefined antibody binding capacity values, limits direct interlaboratory comparison. The present study has addressed these issues using a stable whole blood product and a standardized antigen quantification protocol. It was demonstrated that: (i) a standard technical protocol can result in a high degree of interlaboratory concordance; (ii) interlaboratory variation of less than 12% can be achieved for CD4 antibody binding capacity values; and (iii) stable whole blood can be used as a process control with predefined antibody binding capacity values. Furthermore, using such an approach, a normal range was established for CD3, CD4 CD8 and CD19. These antigens appear to be expressed in a hierarchical manner, a factor that could be used as a procedural quality control measure.

Antigens, CD↗
PubMed2000

Treating fibromyalgia.

Explore the source record for details and available documents.

Antidepressive Agents, Tricyclic↗
PubMed2000

High-producer haplotypes of tumor necrosis factor alpha and lymphotoxin alpha are associated with an increased risk of myeloma and have an improved progression-free survival after treatment.

PURPOSE: To determine the effect of polymorphic variations in the tumor necrosis factor alpha (TNFalpha) and lymphotoxin alpha (LTalpha) genes on the predisposition to myeloma and the effect of these polymorphisms on response to treatment and overall survival. PATIENTS AND METHODS: Genotype distribution was determined in 63 patients with monoclonal gammopathy of uncertain significance (MGUS) and 198 patients with myeloma and compared with that in 250 age- and sex-matched population-based controls. The effect on treatment response and survival was determined in 171 myeloma patients treated with either conventional or high-dose chemotherapy. RESULTS: Comparison of the extended TNFalpha/LTalpha haplotype in the myeloma cases and controls showed a significant excess of high-producer alleles in the cases. The double heterozygotes TNF1/2 and LT10.5/5.5 were present in 35.8% of cases but in only 18% of the controls; this presence was associated with a significant increased risk of myeloma (odds ratio, 2.05; 95% confidence interval, 1.26 to 3.35). A similar odds ratio was seen in the MGUS cases, suggesting that this genotype is associated with the initiation of plasma-cell disorders rather than the progression of MGUS to myeloma. The median overall survival time of myeloma patients was 53.8 months and showed no difference with regard to TNFalpha/LTalpha polymorphic status. A trend toward an improved progression-free survival was apparent in cases with a high-producer haplotype, although this effect was seen only in patients receiving high-dose chemotherapy. CONCLUSION: Individuals with polymorphisms associated with a high production of TNFalpha/LTalpha are at a significantly increased risk of developing MGUS and myeloma. The impact of polymorphic status on overall survival is minimal, although there is a trend toward an increased progression-free survival in the high-producer group.

Adult↗
PubMed2000

Effects of growth hormone and prolactin on hematopoiesis.

The use of the neuroendocrine hormones growth hormone (GH) and prolactin (PRL) in preclinical models, demonstrating promotion of hematopoietic recovery and immune function, offers promise for several clinical situations. These hormones do not appear to produce the same extent of immune/hematopoietic effects when compared to conventional hematopoietic and immune stimulating cytokines (i.e. G-CSF or interleukin-2). However, their pleiotropic effects and limited toxicity after systemic administration makes them attractive to test in myeloablative situations. More work needs to be performed to understand the mechanism(s) of GH and PRL action, particularly with regard to hematopoietic progenitor cell expansion and differentiation both in normal and pathologic situations.

Animals↗
PubMed2000

Clinical examination of varicose veins--a validation study.

The aim of this study was to determine the accuracy of clinical tests compared to colour duplex imaging in patients with primary varicose veins using a prospective, blinded comparison study. A total of 44 patients (70 limbs) with primary, previously untreated varicose veins presenting to the vascular laboratory of a university teaching hospital were studied. The patients underwent physical examination using the cough test, the tap test, Trendelenbergs' test, Perthes' test and hand-held Doppler (HHD) assessment prior to undergoing colour duplex scanning. Reflux was detected on duplex scanning, at the sapheno-femoral junction in 39/70 limbs (54%), the long saphenous vein in 47/70 limbs (64%) and the sapheno-popliteal junction in 9/70 limbs (13%). The cough test had low sensitivity (0.59) and specificity (0.67). The tap test had low sensitivity (0.18) and high specificity (0.92). The Trendelenberg test had high sensitivity (0.91) but low specificity (0.15). Perthes' test had a high sensitivity (0.97) but low specificity (0.20). Hand-held Doppler assessment of reflux at the sapheno-femoral junction, in the long saphenous vein and at the sapheno-popliteal junction had high sensitivity (0.97, 0.82, and 0.80, respectively) and specificity (0.73, 0.92, and 0.90, respectively) of detecting reflux. Clinical tests used in the examination of patients with primary varicose veins are inaccurate. Assessment using hand-held Doppler is more accurate. Courses and clinical textbooks should be revised to replace these tests with instruction in how to use hand-held Doppler in the clinical examination of patients with varicose veins.

Adolescent↗
PubMed1999

Gender differences in symptom presentation associated with coronary heart disease.

This study explores gender differences in symptom presentation associated with coronary heart disease (CHD). In this prospective study, nurse data collectors directly observed 550 patients as they presented to the Emergency Department (ED) of Yale-New Haven Hospital. The final sample included 217 patients (41% women) diagnosed with CHD (acute coronary ischemia or myocardial infarction). Chest pain was the most frequently reported symptom in women (70%) and men (71%). Unadjusted analyses revealed that women were more likely than men to present with midback pain (odds ratio [OR] 9.61, 95% confidence interval [CI] 2.10 to 44.11, p = 0.001), nausea and/or vomiting (OR 2.29, 95% CI 1.19 to 4.42, p = 0.012), dyspnea (OR 1.82, 95% CI 1.05 to 3.16, p = 0.032), palpitations (OR 3.42, 95% CI 1.02 to 11.47, p = 0.036), and indigestion (OR 2.13, 95% CI 1.03 to 4.44, p = 0.040). After adjustment for age and diabetes, women were more likely to present with nausea and/or vomiting (OR 2.43, 95% CI 1.23 to 4.79, p = 0.011) and indigestion (OR 2.13, 95% CI 1.10 to 4.53, p = 0.048). Women (30%) and men (29%) were equally likely to present without chest pain, and dyspnea was the most common non-chest pain symptom. In the subgroup of patients without chest pain, unadjusted analyses revealed that women were more likely to report nausea and/or vomiting compared with men (OR 4.40, 95% CI 1.30 to 14.84, p = 0.013). Although we found some significant gender differences in non-chest pain symptoms, we conclude that there were more similarities than differences in symptoms in women and men presenting to the ED with symptoms suggestive of CHD who were later diagnosed with CHD.

Adolescent↗
PubMed1999

Recognition of medically unexplained symptoms--do doctors agree?

The aim of this study was to investigate the interrater reliability of the recognition of medically unexplained symptoms by medical investigators. The casenotes of 56 consecutive secondary care out-patient attenders were examined by three medical investigators. The investigators determined whether the presenting symptoms were medically unexplained (not, probable, or definite) and the results were tested for interrater reliability. The combined kappa for the three investigators was 0.76, indicating substantial agreement. This suggests that casenote examination is a reliable method of determining whether a symptom is medically unexplained.

Diagnosis, Differential↗
PubMed1999

Prolactin exerts hematopoietic growth-promoting effects in vivo and partially counteracts myelosuppression by azidothymidine.

Prolactin (PRL) is a neuroendocrine hormone that influences immune and hematopoietic development. The mechanism of action of this hormone in vivo remains unclear; therefore, we assessed the effects of PRL on hematopoiesis in vivo and in vitro. Normal resting mice were treated with 0, 1, 10, or 100 microg of recombinant human prolactin (rhPRL) for 4 consecutive days and euthanized on the fifth day for analysis of myeloid and erythroid progenitors in the bone marrow and spleen. Both frequencies and absolute numbers of splenic colony-forming unit granulocyte-macrophage (CFU-GM) and burst-forming unit-erythroid (BFU-e) were significantly increased in mice receiving rhPRL compared to the controls that had received saline only. Bone marrow cellularities were not significantly affected by any dose of rhPRL, but the absolute numbers and frequencies of bone marrow CFU-GM and BFU-e were augmented by rhPRL. These results suggest that rhPRL can promote hematopoiesis in vivo. Because rhPRL augments myeloid development in vivo, we examined the potential of the hormone to reverse the anemia and myelosuppression induced by azidothymidine (AZT). Mice were given rhPRL injections concurrent with 2.5 mg/mL AZT in drinking water. rhPRL partially restored hematocrits in the animals after 2 weeks of treatment and increased CFU-GM and BFU-e in both spleens and bone marrow. The experiments with AZT and rhPRL support the conclusion that the hormone increases myeloid and erythroid progenitor numbers in vivo, and they suggest that the hormone is clinically useful in reversing myelosuppression induced by AZT or other myeloablative therapies.

Animals↗
PubMed1999

The PNH phenotype cells that emerge in most patients after CAMPATH-1H therapy are present prior to treatment.

Paroxysmal nocturnal haemoglobinuria (PNH) cells are deficient in glycosylphosphatidylinositol (GPI) linked antigens due to a somatic mutation of the PIG-A gene in a haemopoietic stem cell. It appears that a PNH clone reaches detectable proportions only when there is selection in its favour. GPI-deficient T lymphocytes have been identified in patients treated with CAMPATH-1H, a monoclonal antibody against the GPI-linked CD52 molecule. CAMPATH-1H selects for cells that are deficient in CD52 (such as PNH-like cells) promoting the development of a PNH-like clone (analogous to PNH). We report that 10/15 patients with chronic lymphocytic leukaemia developed PNH-like lymphocytes after therapy with CAMPATH-1H. The remaining five patients developed no PNH-like cells at any stage, including one patient who received 12 weeks of therapy. The inactivating PIG-A mutation has been identified in one patient. This mutation was detectable by an extremely sensitive mutation-specific PCR-based analysis in the patient's mononuclear cells prior to CAMPATH-1H therapy. The frequency and phenotype of GPI-deficient lymphocytes after CAMPATH-1H and the detection of a PIG-A mutation in the lymphocytes prior to CAMPATH-1H therapy indicated that such mutations were present in a very small proportion of cells prior to selection in their favour by CAMPATH-1H. This suggests that a large proportion of individuals have cells with PIG-A mutations that are not detectable by flow cytometry and thus may have the potential to develop PNH.

Adult↗
PubMed1999

Wet gauze in CO2 laser resurfacing.

The development of scanning CO2 laser systems has enabled rapid and uniform facial resurfacing in photoaged and acne scarred skin. A problem faced by the laser surgeon is making the scanner pattern produced by these lasers fit the cosmetic unit to be resurfaced. This may be achieved by the use of wet gauze to absorb the energy of the unwanted portion of the scanner pattern. The wet gauze is folded to lie along the cosmetic unit boundary and the scanner pattern rotated until it conforms to the required shape. On the eyelids, saline soaked cotton tipped applicators are used to lift the eyelashes away from the path of the laser beam. This allows treatment of the entire lower eyelid cosmetic unit without damage to the eyelashes.

Bandages↗
PubMed1998

Late relapsing childhood lymphoblastic leukemia.

Childhood lymphoblastic leukemia (ALL) is usually assumed to have been permanently eradicated in patients in long-term remission, but occasionally can recur after many years. To learn more about the problem, we studied a group of children whose leukemia had been in remission for 10 or more years before relapse and tried to determine whether they had true recurrences or second malignancies. We studied children treated on Medical Research Council ALL protocols between 1970 and 1984 and followed up by the Clinical Trial Service Unit in Oxford. Detailed clinical and laboratory data was collected from the centers concerned on all who were reported to have had a recurrence of their leukemia after 10 or more years from the time of achieving first complete remission (CR1). To prove that the relapse was a true recurrence rather than a second or secondary leukemia, DNA extracted from archived marrow smears was subjected to polymerase chain reaction (PCR) analysis for the presence of an identical Ig heavy chain (IgH) or T-cell receptor (TCR) gene rearrangement at initial diagnosis and subsequent relapse. A total of 1,134 of 2,746 children had survived 10 years or more (range, 10 to 24 years) in CR1 and of those, 12 (approximately 1%) had subsequently relapsed. Relapse blast cells were shown to express the common ALL antigen (CD 10) in all cases and an identical clonal IgH or TCR gene rearrangement was found on PCR analysis of DNA from diagnosis and relapse in all eight cases where DNA extraction was successful. A further program of therapy was successful in inducing a second CR in all patients, four of whom have succumbed to a second relapse after 12 to 27 months. The remaining eight are in continuing CR2 at a follow-up of 12 to 108 months (median, 52) from relapse. Although the risk of relapse of childhood ALL after 10 years in remission appears to be small (around 1%), it persists. This raises questions about how blasts can survive quiescent for so long and when we can truly be confident of cure, if ever.

Adult↗
PubMed1998

Circulating primitive stem cells in paroxysmal nocturnal hemoglobinuria (PNH) are predominantly normal in phenotype but granulocyte colony-stimulating factor treatment mobilizes mainly PNH stem cells.

Paroxysmal nocturnal hemoglobinuria (PNH) is an acquired hemolytic anemia resulting from a somatic mutation in a hemopoietic stem cell. In most cases of hemolytic PNH, the majority of the marrow cells are derived from the PNH clone. Recent evidence has indicated, however, that the majority of the most primitive peripheral blood stem cells (PBSCs) in PNH appear to be of normal phenotype. This has led to tentative suggestions that normal PBSCs could be collected and used for autologous transplantation. We have investigated this possibility in four PNH patients by treating them with granulocyte colony-stimulating factor (G-CSF) in an attempt to mobilize normal progenitors. The expression of glycosylphosphatidylinositol (GPI)-linked proteins was analyzed by flow cytometry on mature neutrophils, late stem cells (CD34+/CD38+), and primitive stem cells (CD34+/CD38-). The phenotyping and stem cell quantitation was performed in steady-state blood and post-G-CSF administration. The most primitive PBSCs (CD34+/CD38-) were almost all normal before G-CSF treatment, even when the patients' neutrophils were mainly PNH. However, after G-CSF, the cells that were mobilized into the peripheral blood were of a similar phenotype to the mature neutrophils, ie, mainly PNH. It is possible that PNH-stem cells are preferentially destroyed by complement in the peripheral blood leaving only normal cells in the circulation. After G-CSF, the PNH cells in the marrow are released into the blood. Our findings suggest that it would be difficult to collect sufficient numbers of normal stem cells for autologous transplantation.

Adult↗