Search PubMed⌕ Search

Biomedical subjects

L M Nelson

Publications and source records attributed to L M Nelson.

At least 73 records · Page 4Linked to original sources

Completeness and accuracy of interview data from proxy respondents: demographic, medical, and life-style factors.

To evaluate the quality of exposure data provided by proxy respondents, we used a dual interview protocol in a case-control study of subarachnoid hemorrhage. All control subjects and their proxy respondents were interviewed (N = 283 control-proxy pairs), as were the cases who were able to provide their own information and their proxy respondents (N = 68 case-proxy pairs). The reliability of proxy-derived data was excellent for demographic and body habitus measures (kappa or intraclass correlation range = 0.86-0.99), and all aspects of cigarette smoking history (range = 0.79-0.93). Proxy reliability was somewhat lower for questions regarding medications and hormone preparations (range = 0.55-0.88), alcohol consumption (range = 0.52-0.82), and recreational physical activity (range = 0.55-0.67). Proxy reliability varied according to the relationship of the proxy to the index subject. Relative to the index subjects, proxy respondents tended to underreport the presence or level of exposure. For most exposures, odds ratios computed with proxy-derived data were similar in magnitude to odds ratios obtained with index subject data; important bias due to differential nonresponse or differential misclassification was suggested only for questions regarding hormone replacement therapy. Epidemiologic studies that rely on proxy respondents may require more subjects to offset the effect of nondifferential nonresponse and misclassification on the precision of effect estimates.

Adolescent↗

Karyotypically normal spontaneous premature ovarian failure: evaluation of association with the class II major histocompatibility complex.

Patients with premature ovarian failure (POF) have been reported to have an increased frequency of the major histocompatibility class (MHC) class II antigen HLA-DR3. Here we attempt to confirm this association. We performed MHC class II immunophenotyping of HLA-DR antigens 1-10 on 102 North American caucasians with confirmed POF and 102 control caucasian women. All patients had experienced amenorrhea before the age of 40 yr and had elevated serum gonadotropins on repeated study. We found no significant increase in HLA-DR3 frequency in patients with POF when compared to our control group (P = 0.52) or even when compared to a large reference population (n = 1927) that did not differ significantly from our control group (P = 0.47). Our patients did have an increased frequency of HLA DR4 compared to this large reference population (41% vs. 23%; P < 0.001), but we were unable to demonstrate increased HLA DR4 frequency using our control group (31%; P = 0.14). In conclusion, despite a power of 99%, we were unable to confirm a significant increase in MHC class II HLA-DR3 frequency in patients with POF.

Adolescent↗

Development of luteinized graafian follicles in patients with karyotypically normal spontaneous premature ovarian failure.

Despite having amenorrhea and markedly elevated serum gonadotropin levels, some women with karyotypically normal spontaneous premature ovarian failure, nevertheless, have ovarian follicles that function intermittently. Graafian follicles capable of responding to these high FSH levels are faced with high serum LH levels as well, which might induce inappropriate luteinization and prevent normal follicle function. We examined this possibility using weekly blood sampling and sonography in 65 patients. Nearly 50% of our patients demonstrated ovarian follicle function [serum estradiol, > 183 pmol/L (50 pg/mL)] during a median of 4 months of observation (range, 2-6 months). However, during this observation, only 16% achieved an ovulatory serum progesterone level [> 9.5 nmol/L (3.0 ng/mL)]. We imaged an antral follicle by sonography in over 40% of patients (27 of 65), and serum estradiol was significantly greater when an antral follicle was present. The follicles in these patients were not functioning normally, however. In contrast to normal women, patients with ovarian failure had poor correlation between follicle diameter and serum estradiol. We biopsied these antral follicles in 6 patients and found luteinized Graafian follicles in all cases. Therefore, luteinized Graafian follicles account for at least 60% of the antral structures imaged (95% confidence limit). Thus, inappropriate luteinization of Graafian follicles appears to be a major pathophysiological mechanism in patients with karyotypically normal spontaneous premature ovarian failure.

Adult↗

Aberrant hypothalamic-pituitary-ovarian axis in the Watanabe heritable hyperlipidemic rabbit.

The WHHL rabbit has a defective low density lipoprotein receptor and is a model for familial hypercholesterolemia. WHHL rabbits are less fecund than NZW rabbits, the strain into which the defect has been inbred. This lower fecundity could be related to impaired ovarian steroidogenesis due to reduced intracellular availability of cholesterol. Here we compare the WHHL and NZW rabbits with regard to oocyte morphology and fertilization rates after stimulation with equine chorionic gonadotropin. We also compare hypothalamic-pituitary-ovarian axis function by measuring baseline and gonadotropin releasing hormone-stimulated plasma estradiol, progesterone, and gonadotropin levels, both before and after simvastatin inhibition of de novo cholesterol synthesis. WHHL rabbit oocytes remained encased in cumulus and had a lowered fertilization rate (9/50 vs. 83/87, P < 0.05). WHHL rabbits had lower baseline estradiol levels (7.1 +/- 0.72 vs. 10.2 +/- 0.94, P < 0.05) and had higher baseline follicle stimulating hormone (P < 0.05) and luteinizing hormone (P < 0.05) levels. Simvastatin lowered luteal progesterone concentrations only in WHHL rabbits (P < 0.05). We conclude that the hypothalamic-pituitary-ovarian axis in WHHL rabbits is abnormal. The reduced availability of intracellular cholesterol for progesterone synthesis by inhibition of de novo cholesterol biosynthesis leads to a significant reduction in plasma progesterone concentrations in the WHHL. These findings have implications for women with familial hypercholesterolemia, particularly regarding treatment with inhibitors of de novo cholesterol synthesis.

Animals↗

Efficacy of phemister bone grafting in nontraumatic aseptic necrosis of the femoral head.

The authors retrospectively reviewed 40 patients who underwent 52 Phemister bone grafting procedures for nontraumatic aseptic necrosis of the femoral head to better define indications and to evaluate long-term effectiveness of the procedure. The minimum follow-up period was 2 years, and evaluation included physical examination, Iowa hip rating, and radiographs utilizing Marcus and Enneking's staging system. At 2 years following grafting, 13 (76%) of the 17 hips grafted at stage II progressed at least one stage, as did 7 (64%) of the 11 hips grafted at stage III, and 19 (86%) of the 22 hips grafted at stage IV. At the latest follow-up evaluation, 15 (88%) of the 17 hips grafted at stage II progressed at least one stage (follow-up period, 2-10 years), as did 9 (82%) of 11 hips grafted at stage III (follow-up period, 2-10 years), and 21 (95%) of the 22 hips grafted at stage IV (follow-up period, 2-12 years). Twelve (23%) of the 52 hips underwent femoral head or total hip arthroplasty, and the overall Iowa hip rating was 72. The authors' experience confirms reports of other series that do not recommend Phemister bone grafting once collapse is present. The role of structural bone grafting as a temporizing procedure is uncertain.

Adult↗

Clinical course of spontaneous subarachnoid hemorrhage: a population-based study in King County, Washington.

Over 2 years, we identified 171 patients in King County, Washington, experiencing an incident subarachnoid hemorrhage and characterized their clinical course and outcome. Most (65%) were women and most (68%) were under age sixty-five. Only five died without medical attention. The remaining 166 patients were hospitalized and had CTs of the head. Of these, 103 underwent aneurysm surgery, 40 developed acute hydrocephalus, 32 had symptomatic vasospasm, and 30 re-bled. Sixty-eight percent (68%) survived to 1 month after the bleed and 62% to 1 year. Independent predictors of good recovery by 1 month after the bleed included youth, a high score on the admission Glasgow Coma Scale, and absence of blood on the first CT. In this population-based series, at 1 month after the bleed, approximately one-third of patients were dead, one-third had neurologic deficits, and one-third were doing well.

Adult↗

Gonadotropins enhance HLA-DR antigen expression in human granulosa cells.

OBJECTIVES: To determine whether HLA-DR expression in the human ovary is controlled by endocrine or immune mediators, we examined the effects of several lectins, lymphokines, and hormones on granulosa cells in vitro. STUDY DESIGN: HLA-DR antigens were detected by indirect immunofluorescence on granulosa cells obtained at oocyte retrieval for in vitro fertilization. RESULTS: When cultured with concanavalin A, pokeweed mitogen, phytohemagglutinin, interleukin-1, or interleukin-2, granulosa cells failed to express HLA-DR antigens. Both interferon alfa and interferon beta induced only a modest expression of HLA-DR molecules (4.1% +/- 0.9% and 2.5% +/- 0.8%, respectively) in comparison with the marked increase in HLA-DR expression (25.2% +/- 2.8%), when granulosa cells were exposed to interferon gamma. The gonadotropins follicle-stimulating hormone and human chorionic gonadotropin alone were unable to induce HLA-DR antigens, but acted synergistically with interferon gamma to enhance expression in a dose-dependent manner. The addition of 0.1 and 10 IU/ml of follicle-stimulating hormone with 10,000 IU/ml of interferon gamma significantly increased expression by 11.5% +/- 2.5% and 15.5% +/- 2.7%, respectively, over that of interferon gamma alone. Similarly, 1 and 10 IU/ml of human chorionic gonadotropin produced a 7.8% +/- 2.0% and 12.4% +/- 2.2% increase in HLA-DR expression over baseline. CONCLUSION: These studies demonstrate that factors from both the immune and endocrine systems can interact to control HLA-DR expression in the ovary.

Adult↗

Spontaneous abortion and subsequent adverse birth outcomes.

OBJECTIVE: Our purpose was to evaluate the association between spontaneous abortion and subsequent adverse birth outcomes. STUDY DESIGN: Washington State birth certificate records for 1984 to 1987 were used to examine the association between spontaneous abortion and adverse outcomes in the subsequent live birth. Adverse birth outcomes were examined for women with one spontaneous abortion before the index pregnancy (n = 2146) and for women with three or more prior spontaneous abortions and no other prior pregnancies (n = 638); compared with women with no prior spontaneous abortions (n = 3099). Logistic regression was used to estimate the relative risk associated with prior spontaneous abortion of each adverse outcome. RESULTS: Women with three or more prior spontaneous abortions were at higher risk for delivery at less than 37 weeks' gestation (relative risk 1.5, 95% confidence interval 1.1 to 2.1), placenta previa (relative risk 6.0, 95% confidence interval 1.6 to 22.2), having membranes ruptured greater than 24 hours (relative risk 1.8, 95% confidence interval 1.2 to 2.9), breech presentation (relative risk 2.4, 95% confidence interval 1.6 to 3.6), and having an infant with a congenital malformation (relative risk 1.8, 95% confidence interval 1.1 to 3.0). CONCLUSION: These findings suggest that common causes may underlie recurrent spontaneous abortion and certain adverse birth outcomes. They may also help guide clinical management of pregnancies in women with a history of recurrent spontaneous abortions.

Abortion, Spontaneous↗

Gonadotropin suppression for the treatment of karyotypically normal spontaneous premature ovarian failure: a controlled trial.

OBJECTIVE: To determine if gonadotropin suppression improves ovarian follicle function or ovulation rates in patients with karyotypically normal spontaneous premature ovarian failure. DESIGN: Prospective, double-blind, placebo-controlled, crossover trial. SETTING: Tertiary care research institution. INTERVENTIONS: Two intervention phases lasting 4 months each: one placebo phase, and one treatment phase during which each patient received daily subcutaneous injections of 300 micrograms of the gonadotropin-releasing hormone agonist (GnRH-a) deslorelin. During both phases, patients took a standardized estrogen (E) replacement regimen. PATIENTS, PARTICIPANTS: Twenty-six patients with karyotypically normal spontaneous premature ovarian failure ranging in age from 18 to 39 years. MAIN OUTCOME MEASURES: We measured serum estradiol (E2) and progesterone (P) levels weekly during the 2 months after each intervention. We defined a serum E2 greater than 50 pg/mL (184 pmol/L) as evidence for ovarian follicle function and a serum P greater than 3.0 ng/mL (9.5 nmol/L) as evidence for ovulation. RESULTS: The GnRH-a therapy did not significantly enhance recovery of ovarian follicle function or the chance of ovulation. The power to detect a 40% and a 33% ovulation success rate with therapy was 0.95 and 0.83, respectively. We found evidence for ovarian follicle function in 11 of 23 women (48%), and 4 women (17%) ovulated. CONCLUSIONS: Patients with karyotypically normal spontaneous premature ovarian failure treated with E replacement did not benefit from the additional gonadotropin suppression achieved with GnRH-a. Because these patients have a significant possibility of spontaneous remission, attempts to induce ovulation should be limited to controlled trials designed to determine safety and effectiveness.

Adult↗

Influence of metribuzin on the Rhizobium leguminosarum--lentil (Lens culinaris) symbiosis.

The effects of the triazine herbicide metribuzin (Sencor) on the lentil (Lens culinaris Medic.) - Rhizobium leguminosarum biovar viciae symbiosis were studied in Leonard jars and growth pouches. Lentils inoculated with Rhizobium leguminosarum strain 128C54 or 128C84, and noninoculated lentils grown in plant nutrient solution supplemented with 5 mM KNO3, had metribuzin applied to the plants at either 8 or 13 days after planting. When sprayed at 8 days, metribuzin had a significant (p less than or equal to 0.05) negative effect on plant weight, number of nodules, taproot growth, and acetylene reduction activity. Five to 10 days after spraying, the plants began to recover from the inhibitory effects. When spraying was delayed to 13 days after planting, metribuzin had little effect on plant growth. The R. leguminosarum strain used as inoculant affected the degree of inhibition of lentil growth and the rate of plant recovery. Less than 0.2% of foliarly applied metribuzin was translocated to the root. Thus the detrimental effects of metribuzin application to lentils were mainly due to direct effects on the plant, which resulted in indirect effects on nodulation and nitrogen fixation.

Fabaceae↗

Cigarette smoking, alcohol use, and subarachnoid hemorrhage.

BACKGROUND AND PURPOSE: Subarachnoid hemorrhage remains a devastating disease. Identification of etiologic risk factors would allow the possibility of prevention. METHODS: We conducted a population-based case-control study in King County, Washington. Patients whose bleeds originated from a source other than an aneurysm were excluded. Two age- and gender-matched control subjects were identified for each case through random digit telephone dialing. A standardized in-person interview was conducted with the patient whenever possible, a proxy respondent for the case in all instances, the two control subjects, and their proxies. Analyses involved conditional logistic regression taking into account matching on age, gender and respondent type. RESULTS: Over 2 years, 169 cases were identified, and 149 participated in the case-control study. Compared with those who never smoked, the odds ratio for current heavy smokers (greater than 20 cigarettes/day) was 11.1 (95% confidence interval [CI], 5.0-24.9); for current light smokers (less than or equal to 20 cigarettes/day), 4.1 (95% CI, 2.3-7.3); and for former smokers, 1.8 (95% CI, 1.0-3.2). The risk associated with smoking was greatest in the 3 hours after a cigarette (odds ratio [OR] = 7.0; 95% CI, 3.7-13.1) and then fell, not reaching the risk in those who had never smoked until more than 10 years had passed since the last cigarette. Heavy alcohol use (greater than 2 drinks/day) was also associated with bleeds (OR = 2.2; 95% CI, 0.9-5.1, after adjusting for smoking status). These associations were not substantially altered after adjusting for several possible confounding factors, including a history of hypertension. CONCLUSIONS: Cigarette smoking and heavy alcohol use are associated with the occurrence of subarachnoid hemorrhage.

Adult↗

Baclofen effect on quadriceps strength in multiple sclerosis.

Weakness has been reported by patients as one side effect of baclofen. We evaluated torque production as a measure of contractile strength in 30 subjects with clinically definite multiple sclerosis. Participants, with minimal to moderate spasticity, were titrated onto baclofen by 5mg increments every other day for seven days and maintained at 20mg for one week. Using a KinCom isokinetic unit set at 60 degrees per second, subjects performed maximal concentric quadriceps contractions; three consecutive trials were recorded. Results indicated no significant difference in maximum torque production between sessions. Although torque values remained unchanged, the angle at which peak torque production occurred moved closer to normal values. Subjective reports of weakness do not appear related to physiologic properties of contraction, but may be a subjective interpretation that less stiffness is weakness because of less resistance to muscle contraction.

Activities of Daily Living↗

Hypotheses to explain the association between vigorous physical activity and amyotrophic lateral sclerosis.

Many epidemiologic studies indicate a relation between vigorous physical activity and amyotrophic lateral sclerosis. Physical activity itself is unlikely to cause amyotrophic lateral sclerosis, but could it modify the effects of other etiologic factors such as neurotoxins? Vigorous physical activity could potentiate the effect of a toxin to motor neurons by any of several mechanisms, especially if the toxin's effects were mediated through excitation. Exercise could alter the extent of exposure or could influence the distribution, metabolism or potency of an excitotoxin. Future epidemiologic studies of amyotrophic lateral sclerosis should include sufficient detail about vigorous physical exercise to explore this relationship further.

Amyotrophic Lateral Sclerosis↗

Increased peripheral T lymphocyte activation in patients with karyotypically normal spontaneous premature ovarian failure.

OBJECTIVE: To determine if soluble interleukin 2 (IL-2) receptor measured in serum by an enzyme-linked immunosorbent assay (ELISA) might be useful in managing patients with karyotypically normal spontaneous premature ovarian failure. DESIGN: Prospective, controlled observation. SETTING: Tertiary care research institution. INTERVENTIONS: None. PATIENTS, PARTICIPANTS: Twenty-four patients with karyotypically normal spontaneous premature ovarian failure comprised the study group. Forty-two healthy men and women comprised the normal reference group. MAIN OUTCOME MEASURES: We measured peripheral T lymphocyte human leukocyte antigen locus-DR (HLA-DR) expression and IL-2 receptor expression using monoclonal antibodies and flow cytometry. We measured soluble IL-2 receptor levels in serum using an ELISA. RESULTS: Consistent with previous findings, our patients had significantly higher HLA-DR expression on peripheral T lymphocytes (5.3 +/- 0.46) as compared with controls (3.5 +/- 0.34) (mean +/- SEM, P less than 0.01). Seven patients also had elevated IL-2 receptor expression on peripheral T lymphocytes (P less than 0.05). However, soluble IL-2 receptor levels in the serum did not differ significantly from normals. CONCLUSIONS: Patients with karyotypically normal spontaneous premature ovarian failure have a modest increase in peripheral T lymphocyte activation measured by flow cytometry. This degree of activation does not result in increased soluble IL-2 receptor release measured by ELISA.

Autoantibodies↗