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Biomedical subjects

M Elder

Publications and source records attributed to M Elder.

At least 19 recordsLinked to original sources
PubMed2001

Cytokine and chemokine dysregulation in hyper-IgE syndrome.

Hyper-IgE syndrome is characterized by severe recurrent staphylococcal infections, eczema, bone abnormalities, and markedly elevated levels of immunoglobulin E (IgE). The genetic basis is not known and the central immunologic defect is largely undefined. Reduced neutrophil chemotaxis is often described, and variable T cell defects have been demonstrated in some patients. It has been hypothesized that hyper-IgE is associated with a Th1/Th2 imbalance. We wished to characterize cytokine and chemokine imbalances that might reflect the underlying disease process or reflect ongoing pathologic processes. Nine patients with hyper-IgE syndrome and six controls were studied. Radioimmunoassays, flow cytometry, and gene array analyses were performed to characterize cytokine and chemokine production. Hyper-IgE patients express more IL-12, while ENA-78, MCP-3, and eotaxin are markedly underexpressed. Underexpression of a set of chemokines could explain a number of features of hyper-IgE syndrome and may offer a new paradigm for the understanding of this disorder.

Adolescent↗
PubMed2001

PTPRC (CD45) is not associated with the development of multiple sclerosis in U.S. patients.

A C-->G nucleotide transition in exon 4 of PTPRC (encoding protein-tyrosine phosphatase receptor-type C, also known as CD45) was recently reported to be genetically associated with the development of multiple sclerosis (MS). We performed an extensive evaluation of this polymorphism using large family-based and case-control comparisons. Overall, we observed no evidence of genetic association between the PTPRC polymorphism and MS susceptibility or disease course.

Adult↗
PubMed2001

The latanoprost monotherapy survey in New Zealand, 2000.

BACKGROUND: A State subsidy for latanoprost has been recently introduced. It is subject to several conditions including that it should only be used as monotherapy. METHOD: A prospective survey of all New Zealand ophthalmologists was undertaken to determine the outcome of the widespread trial of latanoprost monotherapy. The return rate was 82%. RESULTS: Of 2900 patients on latanoprost nation-wide, 14.7% were monotherapy failures. Of these, 93% were due to inadequate intraocular pressure control but this subgroup had adequate control on two or more medications in 88%. Ophthalmologists had 635 patients that were not trialed as monotherapy, of which 565 (89%) were due to a perceived risk. CONCLUSIONS: In those patients treated with latanoprost, 85% were adequately controlled as monotherapy.

Antihypertensive Agents↗
PubMed2000

The New Zealand cataract and refractive surgery survey 1997/1998.

BACKGROUND: This study documents the current practice for cataract and refractive surgery in New Zealand. METHOD: A postal questionnaire was distributed in late 1997 to all consultant members of the Ophthalmological Society of New Zealand that were resident in the country at that time. Most questions were identical to the 1997 survey of the American Society of Cataract and Refraction Surgeons (ASCRS) to enable a comparison. RESULTS: There were 98 returns from 101 surveys distributed. Of the returns, 72 performed cataract surgery, 23 performed PRK and 11 performed LASIK. ASCRS members did more refractive surgery than did New Zealanders: 28 versus 1% of 1-5 RK per month, 7 versus 1% of 1-2 clear lens extractions per month and 85 versus 51% had access to an excimer laser. For cataract surgery, ASCRS members used more topical anaesthesia (30 vs 5.5%), used no sutures more often (73 vs 51%), used more preoperative antibiotics (76 vs 26%) and used fewer injections of antibiotic/steroids (38 vs 61%). Otherwise the two groups were broadly similar.

Adult↗
PubMed1999

Pre-T cell receptor signals are responsible for the down-regulation of Syk protein tyrosine kinase expression.

Thymocyte development proceeds through two critical checkpoints that involve signaling events through two different receptors, the TCR and the pre-TCR. These receptors employ two families of protein tyrosine kinases to propagate their signals, the Src and Syk families. Genetic and biochemical evidence has shown that the Src family kinases are critical for normal T cell maturation. ZAP-70, a Syk family kinase, has similarly been implicated as a critical component in thymocyte development. Although genetic evidence has suggested that Syk is involved during thymocyte development, a definitive study of Syk expression has not been performed. In this paper we report our reanalysis of Syk expression in subpopulations of murine and human thymocytes by intracellular staining and flow cytometry using anti-Syk mAbs. Syk is expressed at increased levels during the stages in which pre-TCR signaling occurs. Furthermore, Syk is down-regulated after the pre-TCR checkpoint has been passed. Syk may play an important role in thymic development during pre-TCR signal transduction. Finally, incomplete down-regulation of Syk expression was noted in human thymocytes, offering a possible explanation for the distinct phenotypes of mice and humans deficient in ZAP-70.

Animals↗
PubMed1998

T lymphocytes with a normal ADA gene accumulate after transplantation of transduced autologous umbilical cord blood CD34+ cells in ADA-deficient SCID neonates.

Adenosine deaminase-deficient severe combined immunodeficiency was the first disease investigated for gene therapy because of a postulated production or survival advantage for gene-corrected T lymphocytes, which may overcome inefficient gene transfer. Four years after three newborns with this disease were given infusions of transduced autologous umbilical cord blood CD34+ cells, the frequency of gene-containing T lymphocytes has risen to 1-10%, whereas the frequencies of other hematopoietic and lymphoid cells containing the gene remain at 0.01-0.1%. Cessation of polyethylene glycol-conjugated adenosine deaminase enzyme replacement in one subject led to a decline in immune function, despite the persistence of gene-containing T lymphocytes. Thus, despite the long-term engraftment of transduced stem cells and selective accumulation of gene-containing T lymphocytes, improved gene transfer and expression will be needed to attain a therapeutic effect.

Adenosine Deaminase↗
PubMed1996

Effect of matrix metalloproteinase inhibitors on tumor growth and spontaneous metastasis.

Four potent, synthetic inhibitors of matrix metalloproteinases (MMPs) were assessed as inhibitors of tumor growth and spontaneous metastasis to the lung. Mat Ly Lu rat prostate tumor, LOX human melanoma and M27 murine Lewis lung tumor were implanted subcutaneously (s.c.) in mice and allowed to grow for 3-12 days. The lungs of the tumor-bearing mice were then removed and implanted s.c. into untreated mice, and the outgrowth of secondary tumors from the implanted lungs measured. The incidence and rate of outgrowth of secondary tumors increased with the length of primary tumor growth, validating these measurements as indices of spontaneous metastasis to the lung. Compounds were tested by s.c. implantation of minipumps which delivered compound throughout the period of primary tumor growth and spontaneous metastasis to the lung at steady-state drug concentrations orders of magnitude greater than the concentrations needed to either inhibit collagenase, gelatinase or stromelysin in vitro. Inhibitor treatment slowed the growth of primary s.c. Mat Ly Lu and LOX tumors by 40-60% but had no significant effect on the growth of primary M27 tumors. Surprisingly, inhibitor treatment had no significant effect on the ability of the lung to generate secondary tumors when reimplanted s.c. in untreated mice. Because of the possible importance of cathepsins B, H and L in tumor growth and metastasis, the irreversible inhibitor E-64 was also infused by s.c. minipump. E-64 had no effect on the growth or spontaneous metastasis of Mat Ly Lu or M27 tumors.

Animals↗
PubMed1994

Anti-tetanus toxoid antibody production after mismatched T cell-depleted bone marrow transplantation.

We explored B-cell function after tetanus toxoid (TT) immunization in 12 children with severe combined immunodeficiency disease or leukemia who were long-term survivors of an HLA-matched sibling or haplocompatible T cell-depleted parental bone marrow transplant (BMT), 10 of their healthy donors, and 13 normal controls. Specific in vivo and in vitro anti-TT antibody (Ab) production were measured by ELISA. We studied donors' and recipients' peripheral blood mononuclear cells (PBMC) and mixed E- (non-T cells) and E+ cells (T cells) spontaneously and after stimulation by TT in the absence or presence of interleukin-2 (IL-2), IL-4, and IL-6. Five of the 12 patients and all donors and controls responded with in vivo anti-TT Ab. In vitro anti-TT Ab production correlated with the in vivo response. All seven of the nonresponders were either fully engrafted or mixed chimeras (donor T cells but autologous B cells and monocytes). We could not identify a T-cell defect in four of the five nonresponders who were tested. In contrast, E- cells from three of three responders cooperated with fresh donor E+ cells even when they shared only one HLA haplotype. In three of seven nonresponders, in vitro anti-TT Ab production was restored after the addition of IL-4 or IL-6 but not IL-2. Our results suggest that the humoral immunodeficiency that exists post mismatched T cell-depleted BMT is either a B-cell, a monocyte, or a B-cell/T-cell cooperation defect which, in some patients, may be correctible with the addition of a cytokine. Also, it is not necessary to engraft donor B cells to achieve normal antibody responses and the ability to respond does not appear to correlate with pretransplant chemotherapy.

Adolescent↗
PubMed1994

[Triplet and quadruplet pregnancy: management and perinatal outcome].

The frequency of multiple pregnancies with more than two fetuses has increased considerably since the introduction of methods of ovulation induction, in vitro fertilization, and embryo transfer. We have analyzed the evolution, complications, delivery and perinatal outcome of 23 triplet and 3 quadruplet pregnancies occurred during a four-year period in one medical center. The most frequent complication was preterm labor (62%). The mean gestational age at delivery was 32.5 weeks for the quadruplets and 31.5 weeks for the triplets and the mean birth weight was 1461 and 1526 for quadruplets and triplets, respectively. Perinatal mortality for the whole group was 148/1000.

Embryo Transfer↗
PubMed1991

Morphometric study of the human endometrium following continuous exposure to levonorgestrel released from vaginal rings during 90 days.

The effects of vaginal devices releasing levonorgestrel (LNG) at a constant rate of approximately 20 micrograms/24 hrs on the human endometrium were studied in a group of 69 normally menstruating women during a period of 90 days of continuous use. Peripheral blood samples were withdrawn three times weekly starting at day 10 of a pretreatment (control) cycle and then three times weekly from day 60 to 90 of the treatment period. The levels of LNG, estradiol, progesterone and sex hormone binding globulin (SHBG) were analyzed by radioimmunoassay techniques. Endometrial biopsies were obtained in the luteal phase of the pretreatment cycle and on day 84-87 of the treatment period. Increased bleeding occurred in most subjects exposed to the LNG-releasing device; the mean number of bleeding and spotting days was 26.4 +/- 8.9 S.D. which exceeded that found in their control cycle. Morphometric analyses of the endometrial biopsies using 9 quantitative indices, revealed highly significant changes in glands and stroma following the use of the LNG-releasing vaginal device. Irrespective of the circulating steroid levels, the administration of LNG significantly diminished the glandular diameter (p less than 0.001), reduced the volume density of the glands (p less than 0.001) and of the glandular epithelium (p less than 0.001). and modified the ratio glandular epithelium: glands (p less than 0.001). It is concluded that levonorgestrel released at a rate of 20 micrograms/24 hrs, induces characteristic changes in the histologic structure of the human endometrium. Although no simple correlation has been found between any of the endometrial indices and the numbers of bleeding/spotting days or bleeding days, the changes as such may represent biochemical alterations which could be predisposing factors for intermenstrual bleeding and spotting. To prove a causal relationship between morphological and biochemical changes and changes in bleeding patterns, further in-depth studies may be required.

Contraceptive Agents, Female↗
PubMed1990

Treatment of functional menorrhagia by radiofrequency-induced thermal endometrial ablation.

42 patients were enrolled in a trial of radiofrequency-induced thermal endometrial ablation for the treatment of functional menorrhagia. The radiofrequency electromagnetic energy was delivered via a probe placed within the endometrial cavity. 10 patients received 330 kJ of energy, 10 received 445 kJ, and the other 22 received 660 kJ. 19 (87%) of those receiving the highest dose became amenorrheic or had a considerable reduction in menstrual flow. The procedure is simple and the heat induced in the endometrium does not penetrate much beyond the inner layers of the myometrium. There is no need for distension of the uterine cavity with flushing media.

Adult↗
PubMed1990

The effect of prostaglandin synthetase inhibitors on human preovulatory follicular fluid prostaglandin, thromboxane, and leukotriene concentrations.

This study evaluates the eicosanoid concentration in luteinized unruptured follicles (LUFs) on the ovaries of patients who had been treated with inhibitors of prostaglandin synthetase. Indomethacin, bromfenac, or azapropazone (or a placebo) was administered orally to 41 women during the periovulatory period. Follicular development was monitored by serial ultrasound examinations, and the onset of ovulation was regulated by an injection of hCG. Follicular fluid was aspirated during sterilization by minilaparotomy, which was performed just before the expected time of ovulation. Prostaglandin E2 and PGF2 alpha levels in the fluid were significantly reduced by indomethacin and bromfenac compared to those after placebo treatment. Bromfenac also reduced the follicular fluid leukotriene B4 level. Therefore, the development of luteinized unruptured follicles after treatment with nonsteroidal antiinflammatory drugs appears to be associated with a significant decrease in the synthesis of ovarian eicosanoids.

Adult↗