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Biomedical subjects

L Wood

Publications and source records attributed to L Wood.

At least 19 recordsLinked to original sources
PubMed1992

Splenectomy in the chronic myeloproliferative syndromes. A retrospective risk-versus-benefit analysis.

The effect of splenectomy on the course of the chronic myeloproliferative syndromes was retrospectively analysed and compared in 96 patients who underwent this procedure and 195 who did not. The operation had a 4% mortality and a 47% morbidity rate, mainly attributable to haemorrhage, infection and respiratory complications. While splenectomy conferred benefit in certain selected cases with hypersplenism, there was no significant overall improvement in the postoperative haematological values and no influence on the rate of blastic transformation. Splenectomy did not improve survival in the group as a whole, or in any subset (P greater than 0.5). In the non-splenectomy group, only a minority of patients experienced massive progressive splenomegaly and in most individuals the spleen size varied little from the time of presentation to death. Splenectomy in patients with the chronic myeloproliferative syndrome carries a significant mortality and has a high morbidity, does not reduce the rate of blastic transformation and has no influence on survival. The majority of patients on conventional therapy do not experience the discomfort of massive splenomegaly during the course of their disease and the routine use of this operation is inappropriate.

Adolescent↗
PubMed1992

Treatment of acute lymphoblastic leukaemia (ALL).

Forty-six consecutive patients with acute lymphoblastic leukaemia (ALL), having a median age of 23 years (range 14 to 64), underwent induction and consolidation chemotherapy with weekly parenteral vincristine, adriamycin, l-asparaginase and daily oral prednisone (VAAP), followed by standard central nervous system (CNS) prophylaxis. Maintenance therapy was given for 3 years and consisted of daily 6-mercaptopurine, weekly methotrexate, and monthly intrathecal chemotherapy, with drug intensification comprising either vincristine, adriamycin and l-asparaginase (VAA) or cyclophosphamide, vincristine, cytosine arabinoside and prednisone (COAP). Complete remission (CR) was achieved in 36 patients (78%) and only the FAB L1 morphology was a significant predictive factor (Chi-squared = 3.91: p < 0.05). Eight of the 10 non-responders had significant drug resistance and 3 deaths were associated with marrow hypoplasia. Median follow-up is 52 months. Median duration of CR is 28 months, median survival of all patients is 16 months, and for those who achieved CR is 44 months. There was no difference between the two maintenance arms. Significant prognostic factors for survival are French-American-British (FAB) subtype, in which the L1 is better than L2 (p = 0.05), and age (p = 0.035). Nineteen patients have experienced medullary relapse and 7 (37%) achieved subsequent CR; this is durable in a single patient who underwent allogeneic bone marrow transplantation. Eight patients (17%) had CNS disease at diagnosis; 5 achieved CR and 1 is alive and disease-free at 65+ months. There has been 1 CNS relapse. These results demonstrate that prolonged remissions and survival can be achieved with this protocol and many patients possibly cured. The level of toxicity is acceptable and the pattern of induction failure indicates that a margin exists for intensifying chemotherapy and thereby possibly further improving results.

Adolescent↗
PubMed1991

High-sulfur protein gene expression in a transgenic mouse.

We analyzed the effect of minoxidil on hair follicles isolated from transgenic mice. These transgenic animals synthesize the reporter enzyme CAT in their hair follicles only during the active phases of hair growth. The recombinant gene used to generate these mice contained the bacterial enzyme CAT under the control of the promoter from the gene of UHS protein. Studies using in situ hybridization showed that UHS proteins are expressed specifically in the matrix cells of the hair follicle during the terminal stages of hair differentiation. Hence the expression of the UHS proteins is a clear sign of active hair growth. With other in situ hybridization studies we demonstrated that CAT mRNA is expressed in differentiating matrix cells of the hair shaft in a location similar to that in which mRNA encodes UHS proteins. Thus we can use the levels of CAT activity as a measure of hair growth. We have confirmed that expression of the transgene is found in hair that is high in anagen and low in catagen follicles. The usefulness of our model was further demonstrated by showing that minoxidil, a drug that stimulates hair growth, increased the expression of CAT in cultured hair follicles. Thus we have demonstrated that expression of this reporter gene is sensitive, hair specific, and also useful for monitoring effects in cultured hair follicles. Hence these transgenic mice provide a model system for studying the biology of hair growth.

Aging↗
PubMed1991

Failure to establish congenital bluetongue virus infection by infecting cows in early pregnancy.

Two groups of 10 pregnant cows were inoculated with bluetongue virus type 11 at either 40 or 60 days of gestation. All the cows became infected as judged by the detection of viraemia and seroconversion but they showed no clinical signs. Seventeen of the cows produced live calves none of which showed any evidence of prenatal infection. After challenge with the same virus all the calves became viraemic and seroconverted. The response to challenge of the two groups did not differ from that of a control group challenged at the same time. It was concluded that the infection of pregnant cows in early gestation with this virus did not result in the transplacental infection of the fetuses and did not produce immunotolerant, latently infected calves.

Animals↗
PubMed1991

Isolation of a mouse genomic clone containing four tRNACys-encoding genes.

A cluster of four tRNACys-encoding genes with the anticodon GCA was found on a murine genomic clone containing an 18-kb DNA insert. Three of the four genes encode the identical tRNA, whereas the fourth gene has an altered nucleotide (nt) sequence. Two of the genes within a 2-kb PvuII fragment have the same polarity and are separated by only 921 bp. These two tRNAs have a different primary sequence. The changes in the nt sequences occur within three stems of the tRNA cloverleaf structure and weaken the strength of the H-bonds within the stems. All four genes (designated i-iv) have the 3' structural element that has been proposed as the transcription termination signal [Bogenhagen and Brown, Cell 24 (1981) 261-270]. The remainder of the flanking regions of the three identical tRNAs are very similar to each other, whereas the flanking regions of the fourth tRNA are distinctly different.

Animals↗
PubMed1991

Treatment of aplastic anaemia with antilymphocyte globulin and high-dose methylprednisolone.

Twenty-three consecutive adults with bone marrow aplasia who, apart from one individual, lacked a sibling suitable for allogeneic transplantation, received five daily infusions of 50 mg/kg of antilymphocyte globulin (ALG) concurrently with high-dose (500 mg) methylprednisolone (HDMP), followed by oral prednisone at a dose of 30 mg until day 30. One patient died early so that response could not be determined, but data are available and included in the toxicity as well as survival analysis. Haematological response occurred in 13 of the remaining 22 (59%). This followed a single course of treatment in 12, with complete response achieved in five of this group and a second course required in one. At a median follow-up of 20 months (range 5-60), there have been five relapses and 13 patients are alive, including 12 responders who have Karnofsky ratings between 90% and 100%. Of the other nine individuals, only two are alive, with 1 at 12 months still requiring active support and the second, after failing further courses of treatment, at 41 months having a partial response to lymphocytapheresis and plasma exchange. Failure to respond was a significant adverse predictor for survival (P = 0.022). This study involved two distinct batches of ALG, with response occurring in 1/7 (14%) patients treated with the first lot, but in 12/15 (80%) of those individuals who were treated with the second (P = 0.007). Only a pretreatment mean cell volume (MCV) greater than 100 fL predicted for response (P = 0.0088). Confirmation is hereby provided for the efficacy of ALG used in combination with HDMP for treatment of aplastic anaemia, with further support for the observation that not all batches of this product are comparable in bringing about haematologic response in these individuals.

Administration, Oral↗
PubMed1991

Refractory ascites in the chronic myeloproliferative syndrome: a case report.

In a patient with myelofibrosis, tense ascites refractory to conventional therapy resulted from extensive seeding of the peritoneum with colonies of extramedullary haematopoiesis. Whole abdominal radiation was found to be effective and well tolerated, and brought about prompt and lasting resorption of the exudate, with weight reduction and improvement in performance status from 50% to 90% on the Karnofsky rating.

Abdomen↗
PubMed1991

Reactivity of pretransplant cytotoxic antibodies to a selected HLA panel is not influenced by cyclosporin A, with or without plasma exchange.

The influence of 6 weeks of cyclosporin A (CYA), followed by a further 6 weeks of this agent in combination with plasma exchange (PE), was defined on panel reactivity and titre of preformed cytotoxic antibodies in stable patients on haemodialysis awaiting renal transplantation. Nine individuals with antibodies to 30% or more of the donor panel were entered into the study, but three failed to complete the programme. Comprehensive data are available on the remaining six patients, one of whom was studied twice. The pattern of reactivity to the panel was unaltered, but antibody titres were significantly reduced (P less than 0.006). In one patient, a lymphocytoxic crossmatch performed between the patient and an HLA-haploidentical sibling in the last week of the trial was positive, suggesting that neither procedure was successful in removing an antibody directed against the HLA antigens of a family donor. Three cadaver renal transplants were performed during or after the trial, and while two of the grafts were unsuccessful, one survives at 60 months, with good function. From these data it is concluded that neither cyclosporin A nor its combination with plasma exchange have any effect on the panel reactivity of preformed cytotoxic antibodies, whereas the titres were significantly reduced. An important and serious side effect of the apheresis procedure was the loss of fistulae in two patients.

Cyclosporins↗
PubMed1991

Collection and cryopreservation of human stem and progenitor cells for bone marrow transplantation.

Bone marrow collection was undertaken from human organ donors (Group 1: n = 7) to develop a closed-system single-step technique for stem and progenitor cell enrichment, using the Cobe 2997 continuous-flow blood-cell separator. The effects of programmed freezing, storage in liquid nitrogen, and thawing were then defined using these grafts. Once standardised, this method was extended to autografting following cryopreservation of a comparable fraction (Group 2: n = 8) and then to allogeneic transplantation after ex vivo exposure to the lytic monoclonal antibody. Campath-1 IgM and human complement, but without cryopreservation (Group 3; n = 9). The median number of mononuclear cells harvested was 5.0 x 10(6)/mL (n = 24), and this was not significantly different in the three groups. The ex vivo graft, composing marrow rich anticoagulated whole blood, was recirculated in the separator at a flow rate of 60 mL/minute, with a centrifuge speed of 1,100 r.p.m., and the mononuclear cell fractions were collected at the rate of 1.5 mL/minute. The average procedure time from formation of the interface in the single disposable channel to achievement of the final volume was 90 minutes. The mean recovery of the mononuclear cells was 101.4% (SD 38.0) and the GM:CFUc was 91% (SD 43.86). These figures were not significantly influenced by subsequent cryopreservation (Group 1; n = 7 and Group 2; n = 8) or following exposure to the monoclonal antibody. Campath-1 IgM (Group 3; n = 9).(ABSTRACT TRUNCATED AT 250 WORDS)

Bone Marrow Transplantation↗
PubMed1991

Diagnosis of measles by fluorescent antibody and culture of nasopharyngeal secretions.

An indirect fluorescent antibody test (IFA) was evaluated using commercial mouse anti-measles monoclonal antibody and FITC-labeled goat anti-mouse immunoglobulin. For measles isolation, specimens were inoculated into Rhesus monkey kidney (RMK) cells and, when available, CV-1 cells. 381 specimens were tested by IFA and 408 specimens were cultured from patients suspected of having measles. For the 381 specimens tested by both methods, IFA and culture were positive for 31%, culture alone for 14%, IFA alone for 15%, and both negative for 40%. This study indicates that both IFA and culture are required for maximum measles virus detection. Of the positive specimens, 48% were detected either by IFA only (24%) or culture only (24%). IFA was positive in 69% of the culture-positive specimens and therefore, provided rapid diagnosis for many patients.

Antibodies, Monoclonal↗