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Biomedical subjects

A Spencer

Publications and source records attributed to A Spencer.

At least 73 records · Page 4Linked to original sources
PubMed1995

Bone marrow transplantation for chronic myeloid leukemia with volunteer unrelated donors using ex vivo or in vivo T-cell depletion: major prognostic impact of HLA class I identity between donor and recipient.

Between August 1985 and July 1994, we performed 115 volunteer unrelated donor (VUD) bone marrow transplants (BMT) for first chronic phase (n = 86) or advanced phase (n = 29) chronic myeloid leukemia (CML). Standard serologic HLA typing of potential donors and recipients was supplemented with one-dimensional isoelectric focusing (IEF) for class I proteins, allogenotyping for DR and DQ alleles using DNA restriction fragment length polymorphism (RFLP) analysis, and the measurement of antirecipient major histocompatibility complex (MHC) cytotoxic T-lymphocyte precursor cells in the donors' blood (CTLp assay). Recipients were conditioned for transplantation with a combination of high-dose chemotherapy and total body irradiation (n = 103) or high-dose chemotherapy alone (n = 12). Twenty eight recipients received ex vivo T-cell-depleted marrow, and 84 underwent some form of in vivo T-cell depletion. The probability of severe (grades III or IV) acute graft-versus-host disease (aGVHD) was 24%, and that of extensive chronic graft-versus-host disease (cGVHD), 38%. Proportional hazards regression analysis showed an association between low frequency CTLp and a reduced incidence of severe aGVHD (relative risk [RR], 0.28; P = .0035). The probability of relapse at 3 years was 23%, with first chronic phase disease being independently associated with a lower risk of relapse (RR, 0.71; P = .01). The overall leukemia-free survival (LFS) at 3 years was 37%; the LFS for the first chronic phase and advanced phase recipients was 41% and 26%, respectively. First chronic phase disease (RR, 0.56; P = .063) and the combination of recipient cytomegalovirus (CMV) seronegativity and an IEF-matched donor (RR, 0.48; P = .011) were both associated with improved LFS. The probabilities of survival and LFS for patients under 40 years of age transplanted in first chronic phase from an IEF-matched donor were 73% and 50%, respectively. We conclude that VUD BMT is a reasonable option for patients with CML; when using ex vivo or in vivo T-cell depletion, optimal results are achieved in patients transplanted in chronic phase with marrow from donors without demonstrable class I HLA mismatch and a low CTLp frequency.

Adolescent↗
PubMed1995

Cytotoxic T lymphocyte precursor frequency analyses in bone marrow transplantation with volunteer unrelated donors. Value in donor selection.

Between May 1989 and February 1994, we performed 48 volunteer unrelated donor BMTs for first chronic phase chronic myeloid leukemia using in vivo T cell depletion for acute graft-versus-host disease (aGvHD) prophylaxis. In 40 cases, adequate material was available to measure the frequency of antirecipient MHC cytotoxic T lymphocyte precursor (CTLp) cells in the blood of potential donors. This supplemented standard serological typing, one-dimensional isoelectric focusing for class I proteins, and allogenotyping for DR and DQ alleles using DNA RFLP analysis in the donor selection process. All recipients were conditioned with cyclophosphamide 120 mg/kg, TBI 1320 cGy, and intravenous Campath 1G. GvHD prophylaxis consisted of CsA, short-course methotrexate, and intravenous Campath 1G. Minimum follow-up in all surviving recipients was 100 days. The development of aGvHD and the probability of leukemia-free survival were compared between the high frequency group (CTLp > 1 in 100,000) (n = 15) and the low frequency group (CTLp < 1 in 100,000) (n = 25). There was a trend for increasing grade of aGvHD, which was statistically significant in the high frequency group when compared with the low frequency group (P = 0.003). Both a high frequency of CTLp (relative risk [RR] = 9.0, P = 0.016) and HLA mismatch (RR = 6.7, P = 0.023) were predictors of severe aGvHD (grade III or IV). Multivariate analysis showed that CTLp group (RR = 3.4, P = 0.015) and CMV status (RR = 3.9, P = 0.008) were predictors of leukemia-free survival. Further investigation showed an interaction between the two, such that CMV seropositive recipients in the high frequency group had a relative risk of 9.4 (P = 0.0001) of treatment failure (death or relapse) when compared with other combinations. We conclude that with our present GvHD prophylaxis regimen, CTLp frequency analysis predicts post-BMT outcome and is a valuable aid in donor selection.

Adolescent↗
PubMed1995

Intermittent vascular exclusion of the liver (without vena cava clamping) during major hepatectomy.

Intermittent vascular exclusion of the liver (IVEL) combines clamping of the hepatic pedicle with clamping of the main hepatic veins without interruption of caval flow. In this retrospective study, eight cases of total IVEL and eight of partial IVEL were analysed (involving only the middle and left hepatic veins) during major hepatectomy for malignant tumours. Liver parenchyma was pathological in nine cases. IVEL was feasible in 16 of the 18 attempts and was efficient in reducing bleeding during hepatectomy in 15 cases. Mean duration of IVEL was 60.2 (range 37-140) min, mean blood loss was 1230 (range 300-2800) ml and there were no postoperative complications related to the procedure. The major advantages of this technique of liver vascular exclusion (good tolerance and possibility of long duration) merit its inclusion in the list of different clamping techniques available for use during hepatectomy.

Adult↗
PubMed1995

In vivo assessment of catheter-tip PO2 sensor: sampling lumen fabrication.

Fabrication of the sampling lumen of an intra-arterial PO2 sensor is performed in standard catheters mechanically or by laser. Clinical evaluation is performed with respect to catheter insertion, complications, accuracy of oxygen sensor data and fibrin deposition on the catheter surface. The success rate for catheter insertion is 57% for 138 standard and 50% for 74 laser-cut catheters studied. The proportion of catheter failures (blocked or non-reading) is 14% in laser-cut compared with 30% in standard. These differences are not statistically significant at the 5% level. There is no clinically significant difference in sensor accuracy, with 37.5% of results within +/- 0.05 kPa and 80% within +/- 2.0 kPa of simultaneous blood gas values. Drift is within +/- 0.3 kPa h-1 for 78% of monitoring time. Significant errors of recalibration occur in 6% of calibrations. Scanning electron micrographs demonstrate a much smaller sampling lumen in the laser-cut group, but no reduction in fibrin deposition at the site of the sampling hole. The low success rate for catheter insertion is a problem because of cost implications. The accuracy of the system is usually sufficient for clinical purposes, provided the calibration is checked every 4 h.

Catheterization, Peripheral↗
PubMed1995

A common keratin 5 gene mutation in epidermolysis bullosa simplex--Weber-Cockayne.

The Weber-Cockayne subtype of epidermolysis bullosa simplex is an inherited skin-fragility disorder characterized by basal keratinocyte lysis and epidermal blistering confined primarily to the hands and feet. The disorder results from a mutation in either the keratin 5 or keratin 14 gene, which encode the peptide components of the obligate heterodimeric keratin intermediate filaments of the basal cell. We have determined that a T-->G substitution mutation in keratin 5, which results in a Ile-->Ser change at codon 161, is common among patients with the Weber-Cockayne disease variant, accounting for six of 13 cases tested. The observed high frequency of this mutation may result from either a mutational hot spot or a founder effect. The potential utility of this common mutation in confirming disease status in some at-risk individual is discussed.

Base Sequence↗
PubMed1995

Myeloid to lymphoid clonal succession following autologous transplantation in second chronic phase of chronic myeloid leukaemia.

A 23-year-old male found to have Philadelphia chromosome-positive chronic myeloid leukemia (CML) in May 1987 suffered a myeloid blastic transformation in April 1993. A second chronic phase was achieved after treatment with daunorubicin and cytosine arabinoside and the patient then underwent autologous bone marrow transplantation (ABMT) using previously cryopreserved chronic phase bone marrow. Examination of his marrow during the second chronic phase revealed a double Philadelphia chromosome in 15% of metaphases examined and in rearrangement of the immunoglobulin heavy chain gene joining region using Southern blot analysis. Following transplantation, his marrow regenerated into lymphoid blast crisis with three distinct immunoglobulin gene rearrangements visible, one of which corresponded in size to the detected rearrangement pre-transplant. This case is consistent with myeloid to lymphoid clonal succession underlying recurrent blast crises in a patient with CML and suggests the co-existence of both clones prior to ABMT.

Adult↗
PubMed1994

Relapse of chronic myeloid leukemia after allogeneic bone marrow transplant: the case for giving donor leukocyte transfusions before the onset of hematologic relapse.

Fourteen patients with chronic myeloid leukemia (CML) relapsing after allogeneic bone marrow transplant (BMT) were treated with leukocyte transfusions from the original marrow donor (sibling, n = 9; volunteer unrelated, n = 5). The relapse was defined at the molecular level in two cases, cytogenetically in five cases and hematologically in seven cases. Ten patients responded, seven of seven patients with cytogenetic/molecular relapse compared with three of seven with hematologic relapse (P < .03). All five recipients of cells from unrelated donors responded. Eight of the 10 responders have achieved polymerase chain reaction-negative status and this persisted in three patients for more than 2 years; no responder has shown sign of relapse. Reversible marrow aplasia occurred in two patients, both treated in hematologic relapse. Severe graft-versus-host disease occurred in four patients and was fatal in one. We confirm previous reports that donor leukocyte transfusions are effective in the management of CML in relapse after BMT. In this series, therapeutic intervention before the onset of hematologic relapse was associated with an increased likelihood of response and no marrow aplasia.

Adult↗
PubMed1994

An atypical myeloproliferative disorder with t(8;13) (p11;q12): a third case.

A 43-year-old male presented with a myeloproliferative disorder with prominent lymphadenopathy. Examination of the bone marrow showed almost complete replacement by a population of cells with an acquired chromosomal translocation t(8;13)(p11;q12). There are two other case reports describing a similar clinical syndrome with t(8;13)(p11;q12) as the sole chromosomal aberration in bone marrow cells, suggesting a role for this translocation in the pathogenesis of this myeloproliferative disorder.

Adult↗
PubMed1994

High-dose gamma-globulin therapy in the reactive haemophagocytic syndrome.

Reactive haemophagocytic syndrome (RHS) is a disorder characterized by systemic proliferation of non-malignant histiocytes occurring most commonly in patients with pre-existing immunological abnormalities or neoplasms. Patients, particularly those with immunosuppression, often have a rapidly progressive fatal course. Treatment is directed at the underlying disorder. In the absence of identifiable cause, the therapy is less satisfactory. We report here three cases of RHS successfully treated with high-dose gamma-globulin therapy. Two of the three patients were immunocompromised and the third occurred during pregnancy. The improvement occurred within 24-72 h and all patients recovered. High-dose i.v. gamma-globulin therapy may be beneficial in RHS.

Adult↗
PubMed1994

Aplasia after donor lymphocyte infusion (DLI) for CML in relapse after sex-mismatched BMT: recovery of donor-type haemopoiesis predicted by non-isotopic in situ hybridization (ISH).

We report a patient with CML in relapse after a sex-mismatch bone marrow transplant who was treated with donor lymphocyte infusions and developed severe marrow aplasia 3 months later. As cytogenetic analysis at this point was not possible because of the very low number of marrow cells available, we used in situ hybridization (ISH) for sex chromosomes and the BCR/ABL gene together with quantitative PCR to monitor the patient's response. The results suggest that recovering haemopoiesis was derived from donor cells and contributed to the decision not to transfuse donor marrow cells on a second occasion.

Adult↗
PubMed1993

Repeat hepatectomy for cancer.

In a series of 279 hepatectomies performed for cancer between June 1984 and March 1992, 46 were repeat operations, for metastases in 41 patients. The primary tumour was in the colon and rectum (28 patients), APUDoma (five) and miscellaneous (eight). Repeat hepatectomies were performed in 26 per cent of patients who had recurrence after the first liver resection and in 40 per cent of those who had liver recurrence. An unsuspected extrahepatic recurrence was discovered and resected in eight instances and in two other cases a known extrahepatic recurrence was resected during the second hepatectomy. The hospital mortality rate was 2 per cent (one patient); the death was from nosocomial pneumonia. The total morbidity rate including minor complications was 32 per cent, with a higher frequency of haemorrhagic problems after secondary liver resection (12 per cent) than after primary hepatectomy (5 per cent). The rate of postoperative complications after repeat hepatectomy was related significantly to operative blood loss greater than 1500 ml (P = 0.04). The technical problems of repeat hepatectomy were: (1) re-exposure of the liver, considered to be difficult in 67 per cent of second liver resections and 80 per cent of third procedures; (2) the liver parenchyma, which often had histological modifications between first and second resections and was more difficult to 'work' as shown by the mean duration of clamping of the hepatic pedicle (54 min for secondary versus 36 min for primary liver resection); and (3) modification of the intraparenchymal vasculobiliary anatomy following liver regeneration after major hepatectomy. Intraoperative ultrasonography was of great benefit. Rates of crude and recurrence-free survival were relatively encouraging at 47 and 33 per cent 3 years after the second liver resection for the whole group. These values were lower for colorectal cancer (37 and 21 per cent 3 years after the second hepatectomy). These figures do not, however, convey the complete picture of the outcome for these patients. During the same follow-up period, 143 recurrences were detected and a mean of 2.9 resections per patient were performed. The indications for repeat hepatectomy are still to be clarified, although the surgical technique is safe.

Adult↗
PubMed1993

A keratin 14 mutational hot spot for epidermolysis bullosa simplex, Dowling-Meara: implications for diagnosis.

Recently, two patients with the Dowling-Meara subtype of epidermolysis bullosa simplex (EBS-DM) were reported with different mutations in codon 125 of the keratin 14 gene. To determine whether these are common mutations, we screened ten EBS-DM patients and their families using single nucleotide primer extension. Four of ten unrelated EBS-DM patients had a G-->A substitution at base pair 434 of codon 125, whereas one case out of ten had a C-->T substitution at position 433 of the same codon. The G434A alteration cosegregated with the disorder in two multigenerational families; no recombination events were detected. In these two families, linkage analysis provided significant evidence in favor of linkage between G434A and the EBS-DM phenotype, with a LOD score of 3.29 at a recombination rate of 0%. Codon 125 substitutions identified in three unrelated sporadic EBS-DM patients were not found in their clinically unaffected parents. Together, these data provide compelling genetic evidence that the codon 125 substitutions are causal for EBS-DM. The high frequency of mutation at this site in individuals with EBS-DM now makes DNA-based diagnosis of this disorder feasible.

Amino Acid Sequence↗
PubMed1992

Temperature changes during the first day of life in the North Staffordshire Maternity Hospital.

A prospective study of post-delivery temperature changes from birth to 24 h, carried out in a busy District General Hospital is reported. The temperature fall after delivery was less than expected and reflected a high level of awareness of the dangers of hypothermia. On the basis of the findings of the survey, hypothermia in the first 24 h can be defined as a rectal temperature of less than 36.4 degrees C. Those babies who did become hypothermic were significantly more likely to be of low birth weight or preterm gestation.

England↗