PubMed Health⌕ Search

Biomedical subjects

L Porter

Publications and source records attributed to L Porter.

At least 19 recordsLinked to original sources
PubMed1999

Subcellular [Ca2+]i gradients during excitation-contraction coupling in newborn rabbit ventricular myocytes.

The central role of T-tubule and sarcoplasmic reticulum (SR) diadic junctions in excitation-contraction (EC) coupling in adult (AD) ventricular myocytes suggests that their absence in newborn (NB) cells may manifest as an altered EC coupling phenotype. We used confocal microscopy to compare fluo-3 [Ca2+]i transients in the subsarcolemmal space and cell center of field-stimulated NB and AD rabbit ventricular myocytes. Peak systolic [Ca2+]i occurred sooner and was higher in the subsarcolemmal space compared with the cell center in NB myocytes. In AD myocytes, [Ca2+]i rose and declined with similar profiles at the cell center and subsarcolemmal space. Disabling the SR (10 micromol/L thapsigargin) slowed the rate of rise and decline of Ca2+ in AD myocytes but did not alter Ca2+ transient kinetics in NB myocytes. In contrast to adults, localized SR Ca2+ release events ("Ca2+ sparks") occurred predominantly at the cell periphery of NB myocytes. Immunolabeling experiments demonstrated overlapping distributions of the Na(+)-Ca2+ exchanger and ryanodine receptors (RyR2) in AD myocytes. In contrast, RyR2s were spatially separated from the sarcolemma in NB myocytes. Confocal sarcolemmal imaging of di-8-ANEPPS-treated myocytes confirmed an extensive T-tubule network in AD cells, and that T-tubules are absent in NB myocytes. A mathematical model of subcellular Ca2+ dynamics predicts that Ca2+ flux via the Na(+)-Ca2+ exchanger during an action potential can account for the subsarcolemmal Ca2+ gradients in NB myocytes. Spatial separation of sarcolemmal Ca2+ entry from SR Ca2+ release channels may minimize the role of SR Ca2+ release during normal EC coupling in NB ventricular myocytes.

Animals↗
PubMed1999

Calcium modulation of the renin-aldosterone axis.

Changes in the extracellular calcium concentration have important effects on hormone secretion. In vitro, kidney juxtaglomerular cells have been shown to secrete renin in an inverse relationship to the extracellular calcium concentration. The effect of physiologic changes in calcium on renin secretion in humans is less clear. We therefore investigated the effects of physiologic changes in extracellular calcium levels on renin and aldosterone secretion in 7 healthy men. Serum ionized calcium, ACTH, plasma renin activity (PRA), and aldosterone levels were serially measured during 90-min infusions of dextrose, disodium edetate (EDTA) and calcium gluconate, and the latter two infusions were repeated with dexamethasone pre-treatment. ACTH levels decreased during the 5% dextrose in water and the EDTA infusions but increased during the calcium infusion. Similarly, PRA and aldosterone levels fell during the D5W and EDTA infusions but this decrease was absent with increments in calcium levels. Dexamethasone administration suppressed ACTH and the aldosterone response to calcium but did not affect the PRA response to the calcium infusion. Our data indicate that increases in calcium within the physiological range blunt the diurnal decline in both PRA and aldosterone. This appears to be a direct effect of calcium on PRA but mediated through ACTH in the case of aldosterone.

Adrenocorticotropic Hormone↗
PubMed1999

Induction of antitumor immunity after cure of pulmonary metastases, using staphylococcal enterotoxin B and bispecific antibody.

The combination of staphylococcal enterotoxin B (SEB) and anti-p97 x anti-CD3 bispecific antibody (bsAb) cures 60%-80% of mice with established pulmonary metastases of the syngeneic p97+ murine melanoma, CL62. We investigated the ability of cured mice to generate protective antitumor immunity. In tumor rechallenge experiments, CL62-cured mice developed protective immunity against rechallenge with CL62. The majority of mice also rejected the p97-negative parental cell line, K1735, indicating an immune response to tumor antigens common to both cell lines that were not bsAb-targeted. A significant humoral response developed against p97 antigen, but not against other antigens common to both CL62 and K1735. That the majority of cured mice nevertheless rejected K1735 suggests that tumor immunity is not antibody-dependent. Evidence of cellular immunity was obtained from the results of delayed-type hypersensitivity, proliferation and cytotoxicity assays, which revealed the presence of tumor-specific memory in bsAb-treated, CL62-cured mice. CD8+ T cells from cured, but not control mice were able to lyse tumor; however, memory CD4 cells had no cytolytic function. In vivo, however, both CD4 and CD8 T cells were required for effective protective immunity. These studies demonstrate that treatment with SEB and bsAb not only confers passive immune effects of tumor eradication, but also actively promotes the generation of a host antitumor immune response.

Animals↗
PubMed1999

BRCA1 mutations and other sequence variants in a population-based sample of Australian women with breast cancer.

The frequency, in women with breast cancer, of mutations and other variants in the susceptibility gene, BRCA1, was investigated using a population-based case-control-family study. Cases were women living in Melbourne or Sydney, Australia, with histologically confirmed, first primary, invasive breast cancer, diagnosed before the age of 40 years, recorded on the state Cancer Registries. Controls were women without breast cancer, frequency-matched for age, randomly selected from electoral rolls. Full manual sequencing of the coding region of BRCA1 was conducted in a randomly stratified sample of 91 cases; 47 with, and 44 without, a family history of breast cancer in a first- or second-degree relative. All detected variants were tested in a random sample of 67 controls. Three cases with a (protein-truncating) mutation were detected. Only one case had a family history; her mother had breast cancer, but did not carry the mutation. The proportion of Australian women with breast cancer before age 40 who carry a germline mutation in BRCA1 was estimated to be 3.8% (95% CI 0.3-12.6%). Seven rare variants were also detected, but for none was there evidence of a strong effect on breast cancer susceptibility. Therefore, on a population basis, rare variants are likely to contribute little to breast cancer incidence.

Adult↗
PubMed1999

Endocrine effects, efficacy and tolerability of a 10.8-mg depot formulation of goserelin acetate administered every 13 weeks to patients with advanced prostate cancer.

OBJECTIVE: To determine the endocrine effects, efficacy and tolerability of a 10.8-mg depot formulation of Zoladextrade mark (goserelin acetate, Zeneca Pharmaceuticals, Wilmington, Delaware, USA), a luteinizing hormone-releasing hormone agonist analogue, when administration was extended from every 12 weeks to every 13 weeks in patients with advanced prostate cancer. PATIENTS AND METHODS: Between July 1995 and May 1996, 59 patients with either locally advanced (T3 or T4) or metastatic prostate cancer were enrolled in an open-label, multicentre trial. Primary efficacy endpoints were testosterone measurements, and assessments of prostate specific antigen (PSA) response, subjective and objective response. Quality of life (QoL) was a secondary efficacy endpoint. RESULTS: Mean testosterone concentrations decreased to < 0.3 microgram/L by week 4 and remained so for the duration of treatment. There were no statistically significant differences in mean testosterone levels between weeks 12 and 13, or weeks 25 and 26. Serum testosterone suppression was adequate in all 58 evaluable patients at week 13, and 51 of 52 (98%) patients at week 26. Of the 58 evaluable patients, 52 (90%) had a PSA response. A subjective response was recorded for six of 11 evaluable patients. Of 58 patients evaluable for objective response, 46 (79%) had a partial response, three (5%) had stable disease and nine (16%) had objective progression. Except for a significant (P=0.014) decrease in overall sexual interest, QoL was unchanged during therapy. The most common side-effects, regardless of causality, were hot flushes (67%), pain (31%) and pelvic pain (22%). Mild injection-site complaints occurred with only three of 221 (1.4%) depot injections. CONCLUSIONS: Zoladextrade mark 10.8-mg depot, administered every 13 weeks to patients with advanced prostatic cancer, is well tolerated, provides adequate suppression of serum testosterone and produces PSA, subjective and objective responses.

Aged↗
PubMed1999

Hyperglycemia and angiotensin-mediated control of the renal circulation in healthy humans.

Type 1 and type 2 diabetics have an enhanced renal vasodilator response to angiotensin-converting enzyme (ACE) inhibition despite suppressed plasma renin activity (PRA), indicating possible activation of the intrarenal renin angiotensin system. To investigate the role of hyperglycemia, we evaluated the renal hemodynamic response to ACE inhibition in 9 healthy subjects in high-salt balance after steady-state hyperglycemia (8.4+/-1 mmol/L) was achieved via intravenous glucose administration. Renal plasma flow (RPF) and glomerular filtration rate (GFR) responses to captopril and to angiotensin II (Ang II) were measured as paraminohippuric acid and inulin clearances. Hyperglycemia produced a significant increase in RPF of 117 mL. min-1. 1.73 m-2 after 90 minutes but not GFR. Administration of captopril at a dose of 25 mg during glucose infusion led to an increase in RPF of 173+/-24 mL. min-1. 1.73 m-2 (P<0.01) but did not significantly change RPF in the absence of hyperglycemia (7+/-21 mL. min-1. 1.73 m-2). Captopril did not alter GFR in the presence or absence of hyperglycemia. Ang II infusion during hyperglycemia decreased RPF by 45+/-16 mL. min-1. 1. 73 m-2, and this was significantly enhanced by captopril (-98+/-26 mL. min-1. 1.73 m-2, P<0.05). In contrast, there was no enhancement of the vasoconstrictor response to Ang II in the absence of hyperglycemia. PRA did not change with hyperglycemia. Enhancement of renal vasodilation during hyperglycemia by captopril without alteration of PRA suggests activation of the intrarenal renin angiotensin system.

Adult↗
PubMed1998

Stressors and mood measured on a momentary basis are associated with salivary cortisol secretion.

Effects of past, current, and anticipated naturalistic daily stressors and of affect on salivary cortisol levels were examined. Participants (120) reported on stressors and affect 6 x /day in response to a preprogrammed wristwatch. Twenty min after each assessment they took a sample of saliva for cortisol analysis. Both the experience of a current stressor and anticipating a stressor were associated with increased salivary cortisol levels. Average increases in cortisol were relatively low, but inter-individual variability in this response existed. Stressors also were associated with lower positive affect and higher negative affect. Negative affect was associated with higher cortisol levels and positive affect was associated with lower cortisol levels. Daily stressors were not significant predictors of cortisol secretion when affect was controlled. Momentary assessment of daily stressors and of salivary cortisol proved to be a useful tool for examining psychoendocrinological processes in the natural environment.

Adult↗
PubMed1998

Dysversion of the optic disc and axial length measurements in a presumed amblyopic population.

PURPOSE: Our purpose was to evaluate anatomic variations of eyes presumed to be amblyopic. METHOD: Computer imaging and photography of the optic discs of 205 amblyopic subjects were performed and the axial lengths of 183 of the subjects were measured. The paired optic nerve images were evaluated for symmetry of disc contours and orientation of central blood vessels to detect optic nerve head dysversion. Dysversion of the optic nerve head, which is also referred to as segmental hypoplasia, is a congenital disorder characterized by the central retinal vessels emerging temporal to the vertical midline of the disc and being directed nasally or the nerve head tilting in a vertical direction resulting in a downward or oblique tilting of the discs with the blood vessels emerging at the superior or inferior disc rim. RESULTS: Ninety-three subjects had optic nerve dysversion. There was a greater degree of anisometropia (P< or =.004) in subjects with dysversion (anisometropia factor of 2.51+/-2.15) than in the subjects with symmetric discs (anisometropia factor of 1.76+/-1.63). Axial lengths of the amblyopic eyes were significantly smaller (P<.0001) than those of the nonamblyopic eyes. There was no statistical difference (P< or =.879) in length between amblyopic eyes with dysversion and those with symmetric discs. CONCLUSION: Optic disc dysversion was identified in 45.4% of patients who were previously assumed to be amblyopic. There are anatomic malformations in the eyes of a significant proportion of the presumed amblyopic population. This suggests that, in these individuals, congenital peripheral factors rather than impaired cortical development may be responsible for decreased unilateral acuity.

Adolescent↗
PubMed1998

Long-term pamidronate treatment of advanced multiple myeloma patients reduces skeletal events. Myeloma Aredia Study Group.

PURPOSE: To determine the efficacy and safety of 21 monthly cycles of pamidronate therapy in patients with advanced multiple myeloma. PATIENTS AND METHODS: Patients with stage III myeloma and at least one lytic lesion received either placebo or pamidronate 90 mg intravenously administered as a 4-hour infusion monthly for 21 cycles. At study entry, the patients were stratified according to whether they were to receive first-line (stratum 1) or second-line (stratum 2) antimyeloma chemotherapy. Skeletal events (pathologic fracture, radiation or surgery to bone, and spinal cord compression) and hypercalcemia were assessed monthly. RESULTS: The results of the first nine previously reported cycles are extended to 21 cycles. Of the 392 randomized patients, efficacy could be evaluated in 198 who received pamidronate and 179 who received placebo. After 21 cycles, the proportion of patients who developed any skeletal event was lower in the pamidronate-group (P = .015). The mean number of skeletal events per year was less in the pamidronate-group (1.3) than in placebo-treated patients (2.2; P = .008). Although survival was not different between the pamidronate-treated group and placebo patients overall, stratum 2 patients who received pamidronate lived longer than those who received placebo (14 v 21 months, P = .041). Pamidronate was safe and well tolerated during the 21 cycles of therapy. CONCLUSION: Long-term monthly infusions of pamidronate as an adjunct to chemotherapy are superior to chemotherapy alone in reducing skeletal events in stage III multiple myeloma patients, and may improve the survival of patients on salvage therapy.

Diphosphonates↗
PubMed1998

Long-term prevention of skeletal complications of metastatic breast cancer with pamidronate. Protocol 19 Aredia Breast Cancer Study Group.

PURPOSE: Pamidronate, an aminobisphosphonate, has been shown to lower the risk of skeletal complications associated with lytic bone lesions for up to 1 year in women with stage IV breast cancer who received chemotherapy. We studied the long-term effectiveness and safety of continued treatment with intravenous pamidronate infusions for up to 2 years. PATIENTS AND METHODS: Three hundred eighty-two women with metastatic breast cancer and lytic bone lesions who received chemotherapy were randomly assigned to receive either 90 mg of pamidronate or placebo intravenously every 3 to 4 weeks in this double-blind, multicenter, parallel-group trial. Patients were evaluated monthly for 2 years for skeletal complications, which included pathologic fractures, need for radiation or surgery to treat bone complications, spinal cord compression, and hypercalcemia. Bone pain, analgesic use, bone biochemical markers, performance status, quality of life, radiologic response in bone, and survival were also evaluated. RESULTS: As in the first year of treatment, the proportion of patients with any skeletal complication was significantly less for the pamidronate than the placebo group at 15, 18, 21, and 24 months (P < .001). The proportions of patients with any pathologic fracture (i.e., vertebral and nonvertebral fractures), need for radiation or surgery to treat bone complications, and hypercalcemia were also statistically less for the pamidronate than the placebo group. The median time to the first skeletal complication was 13.9 months in the pamidronate-treated women and 7.0 months in the placebo group (P < .001). Long-term treatment did not result in any unexpected adverse events. Survival did not differ between the two groups. CONCLUSION: The risk for osteolytic bone lesion complications in metastatic breast cancer was significantly decreased with monthly infusions of 90 mg of pamidronate, and this effect was maintained for at least 2 years. Pamidronate is a useful adjunct to standard chemotherapy in the palliative treatment of metastatic breast cancer.

Alkaline Phosphatase↗
PubMed1997

Soluble interleukin-2 receptor is a thyroid hormone-dependent early-response marker in the treatment of thyrotoxicosis.

Thyrotoxic patients exhibit increased levels of immune activation molecules (soluble interleukin-2 receptor [sIL-2R], intercellular adhesion molecule-1 [ICAM-1], and endothelial-leukocyte adhesion molecule-1 [ELAM-1]) in serum, although the clinical significance of these measurements remains unclear. In a randomized 4-week study, we have recently shown that in the treatment of hyperthyroidism, the combination of cholestyramine and methimazole (MMI) resulted in faster lowering of serum thyroid-hormone levels than did MMI alone. Stored serial serum samples from patients participating in this randomized treatment trial were analyzed for sIL-2R, soluble ICAM-1 (sICAM-1), and soluble ELAM-1 (sELAM-1). The levels of all three molecules were elevated in patients with hyperthyroidism. Although the levels of sICAM-1 and sELAM-1 remained elevated through the 4-week follow-up period in both groups of patients, the sIL-2R levels (normal levels, 1.0 to 4.2 ng/ml) decreased significantly in the 10 patients who received cholestyramine in addition to MMI (week 0, 14.2 +/- 1.5 ng/ml; week 2, 10.8 +/- 1.2 ng/ml; week 4, 8.9 +/- 1.5 ng/ml). In eight patients who received MMI alone, sIL-2R decreased less rapidly (week 0, 12.3 +/- 1.4 ng/ml; week 2, 12.3 +/- 1.3 ng/ml; week 4, 10.9 +/- 1.3 ng/ml). sICAM-1 and sELAM-1 were elevated at baseline but did not decrease during therapy. In the former group, free thyroxine and free triiodothyronine decreased faster. These data show that levels of sIL-2R in serum, but not those of sICAM-1 and sELAM-1, may be of clinical use in the early follow-up evaluation of medically treated patients.

Antithyroid Agents↗
PubMed1996

Efficacy of pamidronate in reducing skeletal complications in patients with breast cancer and lytic bone metastases. Protocol 19 Aredia Breast Cancer Study Group.

BACKGROUND: Bisphosphonates such as pamidronate disodium inhibit osteoclast-induced bone resorption associated with cancer that has metastasized to bone. METHODS: Women with stage IV breast cancer who were receiving cytotoxic chemotherapy and had at least one lytic bone lesion were given either placebo or pamidronate (90 mg) as a two-hour intravenous infusion monthly for 12 cycles. Skeletal complications, including pathologic fractures, the need for radiation to bone or bone surgery, spinal cord compression, and hypercalcemia (a serum calcium concentration above 12 mg per deciliter [3.0 mmol per liter] or elevated to any degree and requiring treatment), were assessed monthly. Bone pain, use of analgesic drugs, performance status, and quality of life were assessed throughout the trial. RESULTS: The efficacy of treatment was evaluated in 380 of 382 randomized patients, 185 receiving pamidronate and 195 receiving placebo. The median time to the occurrence of the first skeletal complication was greater in the pamidronate group than in the placebo group (13.1 vs. 7.0 months, P=0.005), and the proportion of patients in whom any skeletal complication occurred was lower (43 percent vs. 56 percent, P = 0.008). There was significantly less increase in bone pain (P=0.046) and deterioration of performance status (P=0.027) in the pamidronate group than in the placebo group. Pamidronate was well tolerated. CONCLUSIONS: Monthly infusions of pamidronate as a supplement to chemotherapy can protect against skeletal complications in women with stage IV breast cancer who have osteolytic bone metastases.

Antineoplastic Agents↗
PubMed1996

Efficacy of pamidronate in reducing skeletal events in patients with advanced multiple myeloma. Myeloma Aredia Study Group.

BACKGROUND: Skeletal complications are a major clinical manifestation of multiple myeloma. These complications are caused by soluble factors that stimulate osteoclasts to resorb bone. Bisphosphonates such as pamidronate inhibit osteoclastic activity and reduce bone resorption. METHODS: Patients with stage III multiple myeloma and at least one lytic lesion received either placebo or pamidronate (90 mg) as a four-hour intravenous infusion given every four weeks for nine cycles in addition to antimyeloma therapy. The patients were stratified according to whether they were receiving first-line (stratum 1) or second-line (stratum 2) antimyeloma chemotherapy at entry into the study. Skeletal events (pathologic fracture, irradiation of or surgery on bone, and spinal cord compression), hypercalcemia (symptoms or a serum calcium concentration > or = 12 mg per deciliter [3.0 mmol per liter]), bone pain, analgesic-drug use, performance status, and quality of life were assessed monthly. RESULTS: Among 392 treated patients, the efficacy of treatment could be evaluated in 196 who received pamidronate and 181 who received placebo. The proportion of patients who had any skeletal events was significantly lower in the pamidronate group (24 percent) than in the placebo group (41 percent, P < 0.001), and the reduction was evident in both stratum 1 (P = 0.04) and stratum 2 (P = 0.004). The patients who received pamidronate had significant decreases in bone pain and no deterioration in performance status and quality of life. Pamidronate was tolerated well. CONCLUSIONS: Monthly infusions of pamidronate provide significant protection against skeletal complications and improve the quality of life of patients with stage III multiple myeloma.

Aged↗
PubMed1996

Reactive effects of diary self-assessment in chronic pain patients.

Several studies of experimental and acute clinical pain have indicated reactive effects of self-assessment on pain intensity and tolerance. A recent study of chronic pain patients (vonBaeyer 1994), however, failed to show these effects. The present investigation sought to determine whether reactive effects can be produced in chronic pain patients by an intensive self-assessment protocol. Using the methodology of ecological momentary assessment (EMA; Stone and Shiffman 1994), thirty-five chronic rheumatoid arthritis patients completed diaries of pain and mood seven times a day for 1 wk. Eighteen patients were included in the final sample because they responded to at least half of the number of hourly prompts for each of the 7 days. Using repeated measures analysis of the daily means, no significant effects of time were found for any measures. Reactive effects that result in an average change in pain levels over time, therefore, do not appear to be produced by intensive self-assessment in a naturalistic context. Results are discussed in terms of cognitive and behavioral theories of pain reactivity.

Adult↗
PubMed1996

Conflict.

Conflict management is a major component of a nurse manager's role. How conflict is defined and subsequently approached can determine if its outcome is a positive, growth-enhancing experience, or, if instead, it will have lingering negative effects destined to resurface, provoking further conflict. When conflict progresses without effective intervention, others are drawn, or triangled in, and it becomes difficult to determine how, why, and with whom the conflict began. Approaches range from total avoidance to a fully invested, collaborative process of resolution. The collaborative response demands significant management involvement; however, its outcome can be the discovery of new and better practice opportunities, benefiting all involved.

Conflict, Psychological↗
PubMed1995

Expression of the dihydroorotate dehydrogenase gene, dhod, during spermatogenesis in Drosophila melanogaster.

The dhod gene encodes dihydroorotate dehydrogenase (DHOdehase), which catalyzes the fourth step of de novo pyrimidine biosynthesis. In addition to the common 1.5 kb dhod RNA expressed by embryos and females, adult males produce a group of slightly longer RNAs. Evidence is presented that the latter RNAs arise through transcription initiation at sites upstream from that of the common RNA and expression of these male-specific RNAs is limited to spermatogenesis. In situ hybridization analysis shows that these RNAs accumulate during spermatocyte growth and persist through meiosis and early spermatid differentiation. In contrast, DHOdehase activity is virtually absent in spermatocytes, meiotic cells, and in early spermatid cysts, then it becomes highly abundant in elongated spermatid cysts and disappears in late spermatogenesis. Thus, testis-limited expression of dhod conforms to a model proposed for other genes that function during spermiogenesis: transcription in spermatocytes, storage of translationally inactive RNA through meiosis, translation of the RNA during spermiogenesis. Very similar expression of a testis promoter-lacZ fusion transgene indicates that sequences required for the spermatogenesis transcription and translation patterns are confined to the 5' end of the dhod gene. Deletion analysis of that 5' region delimits all sequences necessary for spermatid expression of the transgene to a 89 bp fragment. These results are discussed in the contexts of known mechanisms of gene regulation during spermatogenesis and potential roles of DHOdehase during spermiogenesis.

Animals↗
PubMed1995

Tumor necrosis factor-alpha affects in vitro hormone production by JEG-3 choriocarcinoma cell cultures.

Steroid hormones, produced by the placenta, appear to be critically important in maintaining the pregnancy of experimental animals and possibly humans. Previous studies in our laboratory have shown that macrophage-conditioned media, which are known to contain several cytokines including tumor necrosis factor-alpha (TNF-alpha), decreased the in vitro synthesis of progesterone (P) and increased the synthesis of estradiol (E2) by placental fragments. The present study was designed to further our understanding of the effect of cytokines on the synthesis of placental trophoblast hormones. The current study shows that TNF-alpha (1-20 ng/ml) decreases the in vitro synthesis of P and increases the synthesis of both E2 and human chorionic gonadotropin (hCG) by JEG-3 choriocarcinoma cells (a model for trophoblast hormone synthesis). The effects of TNF-alpha are independent of changes in formation of adenosine 3':5' cyclic-monophosphate, guanosine 3':5' cyclic-monophosphate, prostaglandin E2, and prostaglandin F2 alpha. However, the effect of TNF-alpha on P formation is blocked by cycloheximide (1 microgram/ml). These observations suggest TNF-alpha could have effects on placental hormone synthesis which might be important in the pathogenesis of both normal and preterm labor. At least some of these effects appear mediated through new protein synthesis.

Choriocarcinoma↗