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Biomedical subjects

L Wood

Publications and source records attributed to L Wood.

At least 91 records · Page 5Linked to original sources
PubMed1996

Fludarabine monophosphate as salvage for refractory chronic lymphocytic leukaemia.

OBJECTIVE: To assess the efficacy of the purine analogue fludarabine monophosphate (FAMP) as salvage therapy in patients at Groote Schuur Hospital with chronic lymphocytic leukaemia (CLL) refractory to standard therapy. DESIGN: Non-randomised trial. SETTING: Tertiary care, referral academic hospital. PATIENTS: Seven patients with B-lineage CLL, 4 in Rai stage IV and 1 each in stages A(I), A(II) and A(III), refractory to treatment with chlorambucil or cyclophosphamide, with or without whole-body irradiation. INTERVENTION: Intravenous FAMP at a dose of 25 mg/m2 daily for 5 days every 28 days. MAIN OUTCOME MEASURES: Partial remission, complete remission, stable disease or progressive disease. RESULTS: Two patients entered CR and 4 PR after a median of 8 courses of treatment (range 2 - 12). One patient died of Pneumocystis carinii pneumonia after 3 courses of therapy. The most common adverse effect of the treatment was myelosuppression, with the nadir of neutrophil counts being less than 0.5 x 10(9)/1 in 5 patients. Three developed infections and required hospitalisation while on therapy. CONCLUSION: FAMP is effective as a cytoreductive agent in patients with CLL refractory to alkylating agents, with or without whole-body irradiation.

Antimetabolites, Antineoplastic↗
PubMed1996

patial pattern analysis of beta-amyloid (A beta) deposits in Alzheimer disease by linear regression.

The spatial patterns of discrete beta-amyloid (Abeta) deposits in brain tissue from patients with Alzheimer disease (AD) were studied using a statistical method based on linear regression, the results being compared with the more conventional variance/mean (V/M) method. Both methods suggested that Abeta deposits occurred in clusters (400 to <12,800 mu m in diameter) in all but 1 of the 42 tissues examined. In many tissues, a regular periodicity of the Abeta deposit clusters parallel to the tissue boundary was observed. In 23 of 42 (55%) tissues, the two methods revealed essentially the same spatial patterns of Abeta deposits; in 15 of 42 (36%), the regression method indicated the presence of clusters at a scale not revealed by the V/M method; and in 4 of 42 (9%), there was no agreement between the two methods. Perceived advantages of the regression method are that there is a greater probability of detecting clustering at multiple scales, the dimension of larger Abeta clusters can be estimated more accurately, and the spacing between the clusters may be estimated. However, both methods may be useful, with the regression method providing greater resolution and the V/M method providing greater simplicity and ease of interpretation. Estimates of the distance between regularly spaced Abeta clusters were in the range 2,200-11,800 mu m, depending on tissue and cluster size. The regular periodicity of Abeta deposit clusters in many tissues would be consistent with their development in relation to clusters of neurons that give rise to specific neuronal projections.

Aged↗
PubMed1996

The lymphomas.

Hodgkin's disease and the malignant lymphomas are, by all available evidence, eminently curable neoplasms. The debates, therefore, on how best the largest numbers of individuals in any community can receive appropriate treatment and this implies their ready access to an experienced multi disciplinary combined clinic. It is important that proper perspective be retained in the African context so that preventive medicine can be employed where appropriate but, based on current understanding, those with lymphoreticular malignancy become immediate beneficiaries of whatever diagnostic and therapeutic resources need to be expended in ensuring optimal outcome. The last word is far from written on how we, as inhabitants of the African continent, will achieve this goal and so measure up to our obligation. However, as resources continue to contract, three observations justify reiteration. Firstly, diagnostic skills need to be honed by experienced pathologists together reviewing all biopsy material and, wherever possible, participating in national or international study groups. Secondly, the silly distinction propagated by some self serving individuals who fantasize that state hospitals and private clinics somehow differ, must be replaced by a more responsible attitude in which resources are pooled in the common quest for maintaining academic standards. Thirdly, given acceptance of the above common sense proposals, a mechanism will exist for the establishment and constant upgrading of national guidelines for management on agreed and achievable protocols. Whilst the theme remains that of tested conventional treatment, flexibility must exist, where appropriate, for palliative care on the one hand with scientific growth and exploration of innovative options on the other. One might conclude by observing that Africa is most certainly unique and this extends to the frequency with which some of these tumours occur; a classical example would be Burkitt's Lymphoma. This places an obligation on all of us to gather and record such experiences and, from this basis, sustain our intellectual drive by forging international bonds with colleagues in the First World. Such collaboration will provide the natural bridge between clinical studies in Africa and the more sophisticated cellular and molecular biology that is being provided by basic scientists in other parts of the world. Such a marriage is practical and both parties stand to gain significantly in the research, development and evaluation of new drugs and protocols that, ultimately, serve the best interests of patients and do so on a world-wide basis.

Africa↗
PubMed1995

Effect of splenectomy on T lymphocyte subsets in patients infected with the human immunodeficiency virus.

A case-control study was conducted at two institutions to determine whether the absolute CD4 lymphocyte count or the percentage of lymphocytes bearing the CD4 marker (i.e., the CD4 percentage) is a more accurate indicator of underlying immune status in splenectomized patients infected with human immunodeficiency virus (HIV). Each of nine splenectomized HIV-infected cases was matched with six nonsplenectomized HIV-infected controls--three matched for CD4 lymphocyte count and three for CD4 percentage. In analyses including the eight cases with an initial CD4 lymphocyte count of > 200/mm3, controlling for the CD4 count revealed differences between cases and controls in terms of CD4 percentage (range, 10%-41% and 17%-54%, respectively; P < .01) and Centers for Disease Control and Prevention (CDC) clinical stage (P = .06). Controlling for the CD4 percentage revealed a significant difference between cases and controls in terms of CD4 count (range, 396-1,040 and 55-784 cells/mm3, respectively; P < .01) but not CDC clinical stage (P > .7). These data suggest that the numerical relationship between the CD4 lymphocyte count and the CD4 percentage among splenectomized HIV-infected patients with more than 200 CD4 cells/mm3 differs from that among nonsplenectomized patients. The CD4 percentage appears to be a more accurate indicator of the underlying level of immune function in the former group of patients.

Adolescent↗
PubMed1994

Construction and features of lambda EMBL3cosW, a lambda replacement vector for detailed analysis of large regions of genomic DNA.

A phage lambda replacement vector, lambda EMBL3cosW, is described which expedites detailed analysis of large regions of chromosomal DNA. Two features of the vector aid this process. Firstly, the replaceable stuffer in lambda EMBL3cosW is flanked by SP6 and T7 promoters so that end-specific hybridisation probes can be rapidly generated from cloned inserts for identification of sequentially overlapping clones in genomic libraries. Secondly, because all the phage coding sequences in the vector (which are placed to the right of the replaceable stuffer) can be removed from cloned inserts by cleavage with NotI, restriction mapping of cloned inserts using partial digest strategies is greatly facilitated. Other features of the vector are: (1) strategically placed BamHI and XhoI sites for the cloning of genomic DNA partially digested with MboI or Sau3AI by two different methods; (2) SalI and SfiI sites for the isolation of intact cloned inserts; and (3) transcription terminators to insulate vector genes from transcriptional interference from cloned insert DNAs.

Bacteriophage lambda↗
PubMed1994

Mapping of 386 kb of genomic DNA in the human dystrophin-encoding gene (DYS) using an ordered phage lambda sublibrary of a YAC clone containing the DYS region.

An integrated restriction map for HindIII and EcoRI has been constructed for 386 kb of the human dystrophin-encoding gene by partial digest mapping of 35 overlapping lambda EMBL3cosW phage clones derived from a yeast artificial chromosome containing this region. Map construction was simplified in two ways. Firstly, the sequence arrangement of lambda EMBL3cosW is such that only map data from cloned inserts are generated using partial digests of lambda phage DNA asymmetrically labelled at the left cos end with a complementary 32P-labelled oligodeoxyribonucleotide. Secondly, the degree of partial digestion was standardised for each restriction enzyme by using ultraviolet light-induced formation of thymine dimers in the recognition sequence to partially block the cleavage reaction. The map provides the basis for work on the analysis of chromosomal rearrangements in this region which give rise to Duchenne muscular dystrophy, and for studies of chromosome structure and function.

Animals↗
PubMed1994

The identification of pathological subtypes of Alzheimer's disease using cluster analysis.

A cluster analysis was performed on 78 cases of Alzheimer's disease (AD) to identify possible pathological subtypes of the disease. Data on 47 neuropathological variables, including features of the gross brain and the density and distribution of senile plaques (SP) and neurofibrillary tangles (NFT) were used to describe each case. Cluster analysis is a multivariate statistical method which combines together in groups, AD cases with the most similar neuropathological characteristics. The majority of cases (83%) were clustered into five such groups. The analysis suggested that an initial division of the 78 cases could be made into two major groups: (1) a large group (68%) in which the distribution of SP and NFT was restricted to a relatively small number of brain regions, and (2) a smaller group (15%) in which the lesions were more widely disseminated throughout the neocortex. Each of these groups could be subdivided on the degree of capillary amyloid angiopathy (CAA) present. In addition, those cases with a restricted development of SP/NFT and CAA could be divided further into an early and a late onset form. Familial AD cases did not cluster as a separate group but were either distributed between four of the five groups or were cases with unique combinations of pathological features not closely related to any of the groups. It was concluded that multivariate statistical methods may be of value in the classification of AD into subtypes.

Aged↗
PubMed1994

Intravenous gammaglobulin has no advantages over oral corticosteroids as primary therapy for adults with immune thrombocytopenia: a prospective randomized clinical trial.

Symptomatic immune thrombocytopenia in adults is potentially lethal, and, when conventionally treated with oral corticosteroid agents, approximately two thirds of patients will have some response in platelet count, but this is seldom durable. Since cytotoxic drugs are of limited benefit at this stage, splenectomy becomes necessary in 70% of patients. Intravenous gammaglobulin has been advocated as an alternative to prednisone as the primary form of treatment. A prospective, randomized comparison was carried out between oral prednisone (1 mg/kg/day; group 1; n = 17), high-dose intravenous gammaglobulin (400 mg/kg on days 1 through 5; group 2; n = 13), or a combination of both agents given on the same schedule (group 3; n = 13). The groups were well matched clinically and hematologically. No mortality occurred after initiating therapy, but one patient experienced a cerebrovascular accident. Response, defined as a platelet count greater than 50 x 10(9)/L, was achieved in 82%, 54%, and 92% of patients in groups 1, 2, and 3, respectively, but was only significant between groups 2 and 3 (P = 0.0365). The median times to peak platelet counts were 8.5 days (range 7 to 21 days), 7 (range 5 to 10 days), and 7 (range 3 to 23 days), respectively. Although there was a trend in favor of the steroid-administered groups, relapse was not significantly different, which occurred at a median of 184, 32, and 76 days, respectively, nor was the average time to splenectomy different at 339, 59, and 98 days, respectively. At a minimum of 2 years of follow-up, 5 of 17 in group 1, 2 of 13 in group 2, and 1 of 13 in group 3 had achieved platelet counts of greater than 100 x 10(9)/L and, therefore, did not require splenectomy. In contrast, where this indication was present for failure to respond, 8 of 12 (67%) in group 1, 4 of 8 (50%) in group 2, and 9 of 12 (75%) in group 3 remain in complete remission. Significantly more patients in group 2 than group 3 experienced a relapse (P = 0.0365). It is concluded that in previously untreated adults with symptomatic immune thrombocytopenia, gammaglobulin offers no advantage over conventional corticosteroid administration as the primary form of therapy. Additionally, more intense immunosuppression, resulting from the use of both agents combined, is no better than single agent corticosteroid agents and appears to be an unnecessary and unwarranted expense.

Administration, Oral↗
PubMed1994

T cell depletion by exposure to Campath-1G in vitro prevents graft-versus-host disease.

Campath-1G is an immunosuppressive monoclonal antibody directed against human lymphocytes. Its effectiveness in preventing graft-versus-host disease (GVHD) by simple opsonisation of bone marrow T-cells has been studied in 36 consecutive allografts: in 17 for leukaemia, one for essential thrombocytosis and four for myeloma this was the sole means of GVHD prophylaxis. A further eight patients with aplastic anaemia received 3 months post-transplantation cyclosporin A (CsA) for this purpose whereas in the ninth and tenth the preparative regimen has been modified with this immunosuppressive agent now discontinued. Nucleated cells were harvested and after quantitative recovery of the mononuclear population on the Cobe 2997 separator they were exposed to 20 mg Campath-1G for 30 min at room temperature and then infused. Following standard conditioning, which included total lymphoid irradiation, the median days to reach 0.5 and 1.0 x 10(9)/l neutrophils were respectively 18 (range 9-34) and 28 (range 10-59); to 25 and 100 x 10(9)/l platelets the corresponding times were 17 days (range 5-32 days) and 27 days (range 13-127 days). In all, the day 14 trephine biopsy showed engraftment. At median follow-up of 20 months (range 5-44 months) only one patient has developed possible grade I cutaneous GVHD that responded promptly to corticosteroids: no chronic GVHD or CMV pneumonitis has been encountered. Of those with haematological malignancy transplanted in remission only two with acute leukaemia have relapsed. In aplastic anaemia graft loss initially occurred but this has been overcome by adding Campath-1G in vivo and omitting CsA.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1993

Cloning, sequencing and expression of a cDNA encoding mammalian valyl-tRNA synthetase.

A fragment of the cDNA encoding a rat valyl-tRNA synthetase (TrsVal)-like protein was cloned from a rat cDNA library in lambda gt11 using an oligodeoxyribonucleotide (oligo) probe. Three independent plaque clones containing the human TrsVal cDNA were then isolated from a lambda gt10 human erythroleukemia cDNA library using the rat cDNA fragment as the hybridization probe. Sequence analyses of the cDNA fragments provided a 3.2-kb sequence with an open reading frame that contained the 'HIGH' synthetase signature sequence and the tRNA 3'-end-binding motif, KMSKS, and putative Val-binding motif, EWCISRQ. The sequence was extended to the 3' end of the cDNA by the polymerase chain reaction using an internal primer and an oligo(dT) adapter. The deduced 1051-amino-acid sequence shares 65% identity with yeast TrsVal, and contains a highly basic N-terminal region, a newly evolved protease-sensitive region in sequence close to the C terminus, and several sites for protein kinase C phosphorylation. A 3-kb cDNA fragment was sub-cloned into plasmid pSVL and expressed in COS-7 cells; up to a sevenfold increase in TrsVal activity was obtained. These results confirm the cloning and sequencing of a human TrsVal-encoding cDNA.

Amino Acid Sequence↗
PubMed1993

Generation of ordered phage sublibraries of YAC clones: construction of a 400-kb phage contig in the human dystrophin gene.

A phage contig of 400 kb that extends from the brain-specific promoter at the 5'-end of the human dystrophin gene, through the muscle-specific promoter over 100 kb further downstream, and across most of intron 1 has been assembled. To achieve this, a yeast artificial chromosome (YAC) subcloning approach was used. Total DNA from a yeast strain containing a 400-kb YAC from the dystrophin gene was cloned using a lambda phage vector containing RNA polymerase promoters flanking the cloning sites. Phage containing human DNA inserts were then ordered into an overlapping set by hybridization of end-specific RNA probes from individual clones back to plaque lifts of gridded phage subclones. The clones generated will be useful as reagents for detailed structural and functional analyses of this region of the dystrophin gene.

Bacteriophages↗
PubMed1993

Plasma exchange for homozygous familial hypercholesterolaemia: the Cape Town experience.

Homozygous familial hypercholesterolaemia (FH) is a rare disorder having a greater frequency in populations with founder effects for the mutations in low density lipoprotein (LDL) receptors. It is characterized by early signs of cholesterol infiltrates with premature coronary artery disease and does not respond to conventional lipid-lowering therapy. Plasma exchange is an established mode of treatment which improves the biochemical abnormality and may allow reversal of the physical manifestations as well as favourably influencing the clinical course of the disease. The efficacy, safety and tolerability of this procedure is confirmed by our experience over the 15 years following the previous report. In a subset of these patients who have residual LDL receptor activity, further lowering of the plasma cholesterol concentration was achieved by adding simvastatin, an hydroxy-methylglutaryl coenzyme A reductase inhibitor. It is concluded that this combined approach may be of benefit in selected cases of homozygous FH undergoing regular plasmapheresis.

Adolescent↗
PubMed1993

Changes in social support and quality of life: a case study of a man with an enduring psychotic illness.

The Government's White Paper on community care has drawn attention to the importance of assessing changes in a person's well-being which occur as a consequence of clinical and social interventions. In the UK the evaluation of the quality of life of people with chronic mental illness is relatively new. This case study demonstrates the use of the 'Lancashire Quality of Life Profile' in routine clinical practice with reference to residential changes in the 'care programme' of a person with a long history of a severely disabling psychotic illness. The formulation and review of his care plan were determined by a network of agencies involved in his long term care.

Activities of Daily Living↗