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Biomedical subjects

E H Jones

Publications and source records attributed to E H Jones.

At least 19 recordsLinked to original sources

Recombinant human erythropoietin.

The characteristics and uses of epoetin alfa (recombinant human erythropoietin) are described, and the issues associated with its use are discussed. The use of epoetin alfa was recently approved by FDA for the treatment of anemia associated with end-stage renal disease. Epoetin alfa acts on burst-forming and colony-stimulating units in the blood to raise hemoglobin and hematocrit levels, thus correcting the patient's anemia. It has a relatively short half-life and may be given either i.v. or s.c. Doses vary and must be adjusted according to the individual patient response. Clinical trials have involved doses ranging from 15 to 500 units/kg three times per week. Treatment causes a dose-related rise in the hematocrit, with subsequent improvement in the quality of life of dialysis patients. Adverse effects include hypertension, iron deficiency, and thrombocytosis. Additional research indicates that epoetin alfa may be effective in the correction of other uncomplicated anemias, such as those related to antineoplastic therapy. Issues facing hospital pharmacists and other health-care professionals include cost (the estimated cost of therapy is $4000 to $8000 per patient per year), appropriate use and potential misuse, use and reimbursement for indications not included in FDA-approved labeling, and restriction to particular prescribers. Because epoetin alfa does not produce therapeutic effects for at least 7 to 14 days, it is an ideal agent for formulary restriction. Epoetin alfa, like other products of biotechnology, will have substantial impact, both therapeutic and economic, on the practice of pharmacy. Hospital pharmacists need to be aware of these new therapies so that they may act quickly and decisively when issues associated with their use arise.

Erythropoietin

Topographic sequence of outgrowth of corticospinal axons in the rat: a study using retrograde axonal labeling with Fast blue.

The retrogradely transported dye, Fast blue, was injected into cervical or lumbar segments of the spinal cord of rats during the first days of life in order to label the cell bodies of origin of the corticospinal tract which is growing down the cord during that period. The first corticospinal axons arrive at cervical levels immediately after birth and all arise from a circumscribed group of layer V pyramidal cells in a small region of dorsal parietal cortex. This same cell group provides the corticospinal projection to lumbar segments of the spinal cord, the axons reaching those segments at the end of the first postnatal week. The area of lumbar projecting cells undergoes relatively little expansion and no diminution during subsequent weeks and into adulthood. The area occupied by cortical cells projecting to the spinal cord expands during the first postnatal week, but the axons of all these additional cells do not appear to invade the lower sequents of the spinal cord. By the end of the first week, corticospinal cells can be labeled in a continuous sheet throughout most of the extent of the frontal, parietal and cingulate cortex. During the second and third postnatal weeks, the area sending axons to the upper levels of the spinal cord diminishes and large areas bereft of retrogradely labeled corticospinal cells appear: laterally, in lateral frontal and lateral parietal cortex; dorsally, at the border of frontal and parietal cortex; medially, in medial frontal and cingulate cortex. The more restricted adult pattern is established at the end of the third week. Hence, the first cortical axons to advance down the spinal cord are those that will innervate the lumbar segments in the adult. Later addition of corticospinal axons involves only those projecting to upper cord segments. Within this group there are those which will establish persistent connections from appropriate cortical areas and others that will shortly be eliminated from inappropriate areas.

Aging

One haplotype matched bone marrow grafts: an investigation using the HLA system as a marker of cellular origin.

HLA antigens were used as markers to study the lymphocyte population in 31 patients with leukaemia, treated with a one-haplotype matched bone marrow transplant (BMT). In 24 patients substained engraftment was achieved and the recipient was repopulated with B and T lymphocytes of donor HLA type. Repopulation occurred at the same rate for lymphocytes of the B and T cell classes, usually within 2 weeks of grafting. In two additional cases bone marrow engraftment was successful but the lymphocyte population was chimeric and cells of both donor and host HLA type were present in the recipient for many weeks. Three patients relapsed after engraftment and peripheral blood lymphocytes were exclusively of host or donor HLA type, or a chimeric population was present. In one chimeric case, peripheral blood T lymphocytes were of donor origin, and B lymphocytes were of host origin. Mononuclear cells in the bone marrow were of host HLA type. The use of the HLA system as a marker is a useful additional approach to determine engraftment or chimerism following an allogeneic one haplotype matched bone marrow transplant.

Adolescent

Call it asthma.

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Asthma

HLA-DR7 association with African Burkitt's lymphoma.

Association between HLA-DR7 and Burkitt's lymphoma previously reported has been confirmed by a second study. Analysis of additional data from a second study of 33 Ghanaian patients with African Burkitt's lymphoma and 54 Ghanaian controls matched for age and ethnic origin showed that 39.4% of cases, but only 14.8% of controls, had HLA-DR7 (p less than 0.01). The relative risk of 3.7 is similar to that observed in the earlier study (3.3). Combining the earlier and present studies, analysis of clinical data from 94 patients with Burkitt's lymphoma and 116 controls shows the relative risk of Burkitt's lymphoma among individuals with HLA-DR7 was 3.4 (p less than 0.001). There was an increased relative risk of the disease associated with HLA-DR7 in: patients under 10 years of age; and patients with advanced stages of disease (Stage III or IV). However, comparison of relative risks by sequential analysis of 2 X 2 tables showed that these differences by age and stage were not statistically significant.

Adolescent

Lymphocytotoxic antibodies in leukemic patients treated with bone marrow transplantation.

Lymphocytotoxic antibodies were studied sequentially in a series of 42 patients with leukemia who received a bone marrow graft. Of these patients, 38% had cytotoxic antibodies before bone marrow transplantation (BMT). After BMT the antibody status changed with time, but 62% of the patients had antibodies at some time after BMT. During the first 10 weeks after BMT, 40% of the patients had antibodies. Thereafter the frequency rose to 50% and remained at that level beyond one year after BMT. In successful grafts the gamma globulins are of donor origin six months after BMT; thus donor B cells are capable of forming lymphocytotoxic antibodies even when the immune system is suppressed by cyclosporine. The antibodies had recognizable HLA specificity in about half the cases before and after BMT. When donor and patient were HLA-identical, HLA specificity did not correspond to donor/recipient antigens. In two cases in which the donor was matched for only one haplotype, antibodies formed by recipient cells, active against donor HLA antigens, were found.

Antilymphocyte Serum

Stimulation by CLL cells in mixed lymphocyte culture (MLC).

Cells from patients with chronic lymphocytic leukaemia (CLL) do not respond in the mixed lymphocyte culture (MLC) but are able to stimulate the response of normal lymphocytes. Mixed lymphocyte cultures were performed using cells from 24 patients with CLL and cells from 16 normal donors. The stimulatory capacity of 8 of these CLL cells was reduced when a common DR antigen was shared with the normal responding cell. We suggest that cells from certain selected CLL patients may be used in the mixed-lymphocyte reaction for determining the D-locus specificity of normal donors. CLL cells when expressed 1 DR antigen only, induced more clearly defined typing responses than cells with 2 DR antigens. There was no correlation between the ability of a CLL cell to induce a typing response and the T-cell status of the patient. However, a correlation with clinical course was suggested, because most cells which induced a typing response were obtained from patients who had received intensive treatment for the disease.

Aged

Protozoan and viral infections of feral cats.

Identification of protozoan oocysts and serological tests were used to determine the prevalence of infections among 300 mainly adult feral cats in three different habitat types in south-eastern Australia. Oocysts of Isospora rivolta and Isospora felis were recovered from 3% and 4% respectively of 300 feral cat samples. Haemagglutination inhibition antibody to Toxoplasma gondii was detected in 20% of 75 cat sera tested. A high prevalence of specific antibody to feline panleukopaenia virus (79%) and feline calici virus (77%) was demonstrated but the prevalence of antibody to feline herpes virus was low (11%). 15 strains of feline calici virus were isolated from pharyngeal swabs. There were no other virus isolations from the 60 pharyngeal and rectal swabs taken. These viral and protozoan infections could not be linked with any obvious pathological conditions. Most cats were in good condition with light to moderate fat stores in depot areas. Limb fractures and other skeletal abnormalities occurred infrequently. Major tooth damage or absence of important teeth was evident in about 20% of 164 animals examined. There was no correlation between major tooth damage and poor body condition.

Animals

Helminth parasites and arthropods of feral cats.

The prevalence (%) of helminth parasites in 327 mainly adult feral cats from 3 habitat groupings in Victoria and New South Wales was determined. The cestodes Taenia taeniaeformis (33%) and Spirometra erinacei (33%) were common; Dipylidium caninum was rate (2%). The nematodes Toxocara cati (28%), Cyathospirura dasyuridis and Cylicospirura felineus combined (27%) and Aelurostrongylus abstrusus (14%) were common but their prevalence differed markedly between habitats. Ollulanus tricuspis (5%), Gnathostoma spinigerum (less than 1%) and an Acanthocephala, Onicola sp (19%), also occurred. Arthropod parasites were collected from 204 of these cats, Ctenocephalides felis (16%) and Echidnophaga spp. (28%) were common. Spilopsyllus cuniculi (3%) and Ctenocephalides canis and Nosopsyllus fasciatus (less than 1% each) were rare. Other rare ectoparasites were the louse, Felicola subrostrata (4%), the mites, Otodectes cynotis, Cheyletiella sp and a trombiculid (less than 1% each); and the tick lxodes tasmani (less than 1%). There was no correlation between degree of parasitism and general condition of the cats.

Animals

Study of the HLA system in Burkitt's lymphoma.

Seventy-eight patients with Burkitt's lymphoma and seventy controls from Ghana were typed for HLA-A, B, C and DR antigens, to determine whether there is an association between the HLA system and Burkitt's lymphoma. Increased relative risk was observed in Burkitt's lymphoma patients with DR7, HLA-A1 and B12(BW44).

Adolescent

Antisera with Ia specificity selected by lymphocytes from patients with chronic lymphocytic leukemia.

Cells from patients with chronic lymphocytic leukaemia (CLL) have been used to screen the sera of pregnant women for antibodies specifc for B lymphocytes. The sera have been divided into groups showing Ig specificity: group I (UK 3) had a positive association with HLA-B8 and DW3, and group II (UK 2) with HLA-B7 and DW2. Groups III, IV and X were independent of each other and of HLA-A, B and C locus antigens. Certain sera with B-cell activity showed specific blocking activity in the mixed lymphocyte reaction (MLR), and this activity was dependent on the Ia sepcificities and DW specificities of cells used in the MLR. Some sera specifically blocked the responding cells, other the stimulating cells.

Antibody Specificity