Biomedical subjects

L M Nelson

Publications and source records attributed to L M Nelson.

At least 19 recordsLinked to original sources

PubMed1996

Cost effectiveness of use of a solution of 6% dextran 70 in young calves with severe diarrhea.

OBJECTIVE: To determine whether intravenous administration of 6% dextran 70 solution to young calves with severe diarrhea is cost effective. DESIGN: Randomized, prospective, clinical trial. ANIMALS: 22 calves < 2 months old that were hospitalized for diarrhea and that did not have pneumonia. PROCEDURE: All calves received antibiotics, were fed by use of an orogastic tube, were supplied with radiant heat, and were given crystalloids, i.v., as deemed appropriate by an attending veterinarian. A group of 12 calves also received 500 ml of 6% dextran 70 solution, i.v., over a 1-hour period as part of the initial treatment. Data were collected to determine whether early treatment with 6% dextran 70 solution resulted in a similar end cost for treatment because of a decrease in the volume of fluids administered i.v., a decrease in antibiotic usage, a decrease in the amount of time hospitalized, or a decrease in mortality. RESULTS: Capillary refill times, heart rates, respiratory rates, and rectal temperatures; and scores for dehydration, mucous membrane color, lung sounds, mental status, and suckling response were not different between the 2 groups of calves at admission. Differences were not detected in client charges or in hospitalized time (6% dextran 70 group, $89.68 +/- 11.05 and 36 +/- 3 hours; control group $88.02 +/- 4.93 and 36 +/- 4 hours), but those charges did not include costs for the 6% dextran 70 solution. CLINICAL IMPLICATIONS: Use of 6% dextran 70 solution as part of the resuscitation of most young calves with diarrhea requiring hospitalization is not likely to be cost effective.

Animals↗

PubMed1996

Randomized trial of leaving messages on telephone answering machines for control recruitment in an epidemiologic study.

To determine whether leaving messages on answering machines would aid control recruitment via random-digit telephone dialing, a randomized trial was conducted during 1992-1994 involving 1,323 western Washington households with answering machines. For the experimental group, a message was left informing them about the study and promising a call-back; for the control group, no message was left. Leaving a message increased the response rate by about 20 percentage points (p = 0.002). More households were successfully screened for eligible controls, and individuals found eligible were more likely to participate. Leaving a message can help to improve response rates in telephone surveys.

Adult↗

PubMed1996

The factor V Leiden mutation may predispose women to severe preeclampsia.

OBJECTIVE: A recent study showed that resistance to activated protein C may underlie some cases of severe preeclampsia. A common missense mutation in the factor V gene, the Leiden mutation, is the most frequent genetic cause of resistance to activated protein C. Our objective was to determine whether this mutation is more prevalent in patients with severe preeclampsia than in normotensive controls. STUDY DESIGN: Deoxyribonucleic acid was extracted from whole blood of 158 gravid women meeting criteria of The American College of Obstetricians and Gynecologists for severe preeclampsia and 403 normotensive gravid women. The polymerase chain reaction was used to amplify exon 10 of the factor V gene, followed by allele-specific restriction with Mnl 1 for mutation detection. Results were analyzed with a chi(2) contingency table. RESULTS: No patients were homozygous for the Leiden mutation. Fourteen of 158 women with severe preeclampsia (8.9%) were heterozygous for the Leiden mutation compared with 17 of 403 normotensive gravid controls (4.2%). The difference in frequency between women with severe preeclampsia and normotensive controls was statistically significant, chi(2) 4.686, p = 0.03. CONCLUSIONS: Our data suggest that carriers of the factor V Leiden mutation are at increased risk for severe preeclampsia. Deoxyribonucleic acid analysis for the factor V Leiden mutation could serve as one component of a genetic screening profile for preeclampsia and other adverse pregnancy outcomes. Women who carry this mutation are at increased risk for deep venous thrombosis. Carriers of this common thrombophilic mutation may be identified so that adequate counseling regarding future contraceptive usage and effective thromboembolic prophylaxis during pregnancy and surgical procedures may be offered.

Adult↗

PubMed1996

Susceptibility to murine experimental autoimmune oophoritis is associated with genes outside the major histocompatibility complex (MHC).

PROBLEM: Neonatal thymectomy induces experimental autoimmune oophoritis in certain strains of mice, and this serves as a model for human autoimmune oophoritis. Because strong MHC associations have been noted in human autoimmune conditions, we investigated the role of MHC in determining susceptibility to murine experimental autoimmune oophoritis. Strain A mice are highly susceptible to post-thymectomy autoimmunity, whereas strain B10 mice are relatively resistant. The availability of congenic strains of mice makes it possible to separate the effects of genetic background and specific H-2 haplotype METHODS: We neonatally thymectomized A and B10 background female mice, and their H-2 congenic counterparts, and then evaluated the resulting ovarian disease at age 6 weeks. RESULTS: A. By mice, which have the A background and the H-2b haplotype, developed severe disease equivalent to strain A mice. Similarly, B10.A mice, which have the B background and the H-2a haplotype, failed to develop disease. Thus, H-2a haplotype did not convey disease susceptibility. CONCLUSIONS: Our findings suggest that immune-regulatory regions outside the H-2 locus play an important role in determining susceptibility to murine post-thymectomy autoimmune oophoritis. This is in accord with our previous findings in women that showed no association between MHC and premature ovarian failure. Thus, in this respect this model is similar to human autoimmune ovarian failure. This suggests that the non-MHC genes conveying susceptibility to autoimmune oophoritis in mice might represent similar predisposing genes for premature ovarian failure in women.

Animals↗

PubMed1996

Glycoprotein hormone alpha-subunit functions synergistically with progesterone to stimulate differentiation of cultured human endometrial stromal cells to decidualized cells: a novel role for free alpha-subunit in reproduction.

Glycoprotein hormone-free alpha subunit is secreted by the pituitary throughout the menstrual cycle and by the placenta during pregnancy. We showed previously that free alpha subunit stimulated PRL secretion from term pregnancy decidual cells, suggesting a function for free alpha in pregnancy. However, no role has been ascribed to free alpha in the normal menstrual cycle. Using an in vitro model, we examined the role of alpha subunit in regulating human endometrial stromal cell differentiation (decidualization). PRL and insulin-like growth factor binding protein-1 (IGFBP-1), specific decidual secretory products, were used as markers of decidualization. We found that alpha subunit acted synergistically with progesterone (P) to induce more rapid decidualization with higher output (2- to 6-fold) of PRL and IGFBP-1, compared with P alone (P < 0.01). The effect of alpha was dose dependent, with stimulatory activity starting at 0.05 ng/ml and reaching maximal levels at 1-2 ng/ml. These levels correspond to serum concentrations of free alpha found during the luteal phase of the menstrual cycle when endometrial decidualization occurs in vivo. These findings demonstrate new biological activity for alpha subunit in the regulation of human endometrial decidualization and indicate that free alpha plays a role in human reproduction. Furthermore, demonstration of potential bioactivities of free alpha subunit has important implications for understanding normal endocrine function and various pathological conditions.

Adult↗

PubMed1996

Genotyping of PCR-based polymorphisms and linkage-disequilibrium analysis at the NF1 locus.

Six polymorphisms across the NF1 gene have been adapted for genotyping through application of PCR-based assays. Three exon-based polymorphisms--at positions 702, 2034, and 10647 in the NF1 cDNA--were genotyped by mutagenically separated PCR (MS-PCR). A fourth polymorphism, DV1.9, is an L1 insertion element in intron 30, and the other two polymorphisms, GXAlu and EVI-20, are short tandem repeats in intron 27b. All the polymorphisms were evaluated in a cohort of 110 CEPH individuals who previously had been analyzed by use of eight RFLPs at the NF1 locus. Pairwise linkage-disequilibrium analyses with the six PCR-based polymorphisms and their flanking markers demonstrated disequilibrium between all tested loci. Genotypes of the four diallelic polymorphisms (702, 2034, 10647, and DV1.9) were also evaluated in cohorts from the CEPH, African, and Japanese populations. The CEPH and Japanese cohorts showed similar heterozygosities and linkage-disequilibrium coefficients. The African cohort showed a higher degree of heterozygosity and lower linkage-disequilibrium values, compared with the CEPH and Japanese cohorts.

Alleles↗

PubMed1995

The effect of operative position on lumbar lordosis. A radiographic study of patients under anesthesia in the prone and 90-90 positions.

STUDY DESIGN: The effect of intraoperative positioning on lumbar lordosis was retrospectively studied by radiographic analysis of 40 patients under general anesthesia. OBJECTIVES: The aim of this study was to document changes in segmental and total lumbar lordosis between preoperative standing and intraoperative radiographs taken in the "90-90" and prone positions. SUMMARY OF BACKGROUND: Preservation of physiologic lordosis was an important consideration in reconstructive lumbar spine surgery. To avoid iatrogenic loss of lordosis when using spinal instrumentation and to facilitate decompressive procedures, it was necessary to understand how segmental alignments were affected by intraoperative positioning. Although many positioning techniques were used, the effect on lumbar lordosis was not well established. METHODS: Preoperative (standing 36" lateral spine) and intraoperative radiographs (lateral lumbar spine L1 to the sacrum) in either the "90-90" position on a Hastings frame (n = 20) or the prone position on a Jackson table (n = 20) were measured twice by two independent observers using Cobb methodology for total and segmental lordosis between L1 and S1. Data were analyzed for intra- and interobserver reliability and changes in segmental and total lordosis between standing and intraoperative radiographs. RESULTS: Analysis of intra- and interobserver reliability revealed measurements were accurate and reproducible. The "90-90" position produced significant loss (P < or = 0.01) of total and segmental lordosis at all levels except L1-L2, which showed no change. Segmental lordosis was reduced nearly 60% at L2-L3, L3-L4, and L4-L5, and total lordosis was reduced by more than 35%. The prone position on the Jackson table increased segmental lordosis at L5-S1 by 22% (P < or = 0.01) and preserved total and segmental standing lordosis at all other levels. CONCLUSIONS: The "90-90" position on the Hastings frame was associated with significant reduction of total and segmental lordosis in the middle and lower lumbar spine. Positioning prone on a Jackson table maintained standing lumbar lordosis and increased lumbosacral lordosis.

Adult↗

PubMed1995

Inhibition of zona pellucida gene expression by antisense oligonucleotides injected into mouse oocytes.

During murine oogenesis, the zona pellucida proteins (ZP1, ZP2, and ZP3) are synthesized and secreted to form an extracellular matrix that surrounds the oocyte and mediates specific biological functions essential to mammalian fertilization and early development. To investigate the relationship among the zona proteins during zona matrix assembly, we have undertaken to inhibit de novo biosynthesis of specific zona proteins with antisense oligonucleotides complementary to the 5'-ends of ZP2 (nucleotide position 19-42) and ZP3 (nucleotide 21-44) mRNAs. When injected into the cytoplasm of growing mouse oocytes, the antisense oligonucleotides targeted specific zona mRNAs for degradation, as confirmed by a RNase protection assay. Individual zona pellucida protein synthesis was followed by immunoprecipitation with ZP2- and ZP3-specific monoclonal antibodies. New zona protein synthesis from the targeted mRNA was abolished, but nontargeted zona protein continued to be synthesized. Interestingly, abolishment of either ZP2 or ZP3 protein synthesis prevented the incorporation of the other protein into the extracellular zona matrix. These results suggest that ZP2 and ZP3 proteins are independent of each other in their biosynthesis but are dependent upon each other for their incorporation into the zona pellucida matrix. This study provides an experimental system in which destruction of a targeted mRNA generates a transient loss-of-expression phenotype during mouse oocyte growth.

Animals↗

PubMed1995

Anamnestic development of lymphocytic infiltration in murine experimental autoimmune oophoritis is primarily localized in the stroma and theca.

PROBLEM: Neonatal thymectomy performed on day 3 of life (NTX3) induces autoimmune oophoritis and ovarian failure in B6A mice. These mice develop high-titer autoantibodies specific to oocytes, and ultimately the ovaries become fibrotic and devoid of primordial follicles. These findings implicate the oocyte as a primary target of the autoimmune process. However, in previous work we demonstrated that in developing disease the lymphocytic infiltration was confined to the stroma and theca, and not found involving oocytes. Here, we investigate the possibility that lymphocytic infiltration involving oocytes develops as part of end-stage disease. METHOD: We transplanted normal syngeneic ovaries to B6A mice with confirmed autoimmune ovarian failure, and, as a control, to normal oophorectomized mice. We then defined the time course and histologic distribution of lymphocytic infiltration in the transplanted ovaries. Lymphocytes were identified by morphology with the aid of an immunohistochemical leukocyte marker (CD45). RESULTS: Autoimmune oophoritis developed by 7 days after transplantation to the NTX3 mice. Compared to control mice, in these mice we found significantly increased stromal and thecal lymphocytic infiltration. In no case did we observe lymphocytic infiltration involving oocytes. CONCLUSIONS: Our findings agree with our previous report and suggest that the ovarian failure in this model is not mediated by a direct lymphocytic attack against intact oocytes. Other immune-mediated mechanisms are responsible. The paradoxical development of high-titer oocyte-specific antibodies despite the stromal and thecal location of the lymphocytic infiltration remains to be explained.

Animals↗

PubMed1995

Murine experimental autoimmune oophoritis develops independently of gonadotropin stimulation and is primarily localized in the stroma and theca.

PROBLEM: Neonatal thymectomy performed on day 3 of life (NTX3) induces experimental autoimmune oophoritis in certain strains of mice. The disease has its onset around the time of the first estrous, suggesting the process may be gonadotropin dependent. Furthermore, one study reported that gonadotropin stimulation exacerbated the ovarian lymphocytic infiltration in NTX3 mice. Here we examine the possibility that gonadotropin stimulation of the ovary plays a role in the development of post-thymectomy autoimmune oophoritis. METHOD: Using immunohistochemistry we defined the time course and histologic distribution of the post-thymectomy ovarian lymphocytic infiltration that develops in B6A mice ([C57BL6 X A/J]F1). We detected ovarian leukocytes using a monoclonal antibody against mouse CD45/T200 and counted those positive staining cells that had the morphologic appearance of lymphocytes. We then treated NTX3 mice to determine if gonadotropin stimulation could exacerbate the disease or cause the disease to appear earlier. We also treated NTX3 mice to determine if gonadotropin suppression could reduce the severity of the disease. RESULTS: Ovarian lymphocytic infiltration was observed as early as 3 weeks after thymectomy, and, during the course of the disease, was primarily located in the stroma and theca. Gonadotropin stimulation did not exacerbate existing disease or induce an earlier onset of severe disease. Furthermore, gonadotropin suppression did not reduce the degree of lymphocytic infiltration or oocyte destruction. CONCLUSIONS: Our findings suggest that murine experimental autoimmune oophoritis develops independently of gonadotropin stimulation of the ovary.

Amino Acid Sequence↗

PubMed1995

Low birthweight infants and total parenteral nutrition immediately after birth. II. Randomised study of biochemical tolerance of intravenous glucose, amino acids, and lipid.

This randomised study aimed to compare the biochemical tolerance of three parenteral regimens administered during the first 48 hours of life. Twenty nine infants were randomised to either: (a) glucose 10%; (b) glucose 10%/amino acids; (c) glucose 10%/amino acids/lipid. Blood samples for plasma amino acid profiles, cholesterol, and triglyceride concentrations were taken on arrival in the neonatal unit and again between 36 and 48 hours of life. Arterial or capillary blood gas analysis and blood glucose estimates were performed routinely during the first 48 hours of life. There was a sharp decline in plasma amino acid concentrations in the group following (a) compared with the two groups following (b) and (c) regimens. In all groups plasma triglyceride and cholesterol were not significantly different before and after 48 hours of lipid infusion. Peak mean (SE) bilirubin concentrations (203 (12) v 181 (19) v 220 (20) mumol/l) and the need for phototherapy (nine v eight v five infants) were similar for each of the groups. Hypoglycaemia occurred most frequently during the (b) regimen and least commonly in the (c) group. There are potential health gains from giving parenteral nutrition to low birthweight infants immediately after birth, and this study indicates that restriction of nutritional intake immediately after birth in preterm infants may cause significant metabolic disturbance. This can be prevented by starting a regimen of intravenous amino acids and lipid immediately after birth.

Amino Acids↗

PubMed1995

A potential novel mechanism for precocious puberty in juvenile hypothyroidism.

Some children with juvenile hypothyroidism exhibit unexplained precocious puberty. Interaction of TSH with the human FSH receptor (hFSH-R) is a possible pathophysiological mechanism for this syndrome that has not been explored due to the lack of hFSH-free TSH preparations and the scarcity of a suitable hFSH-R-based assay system. To devise an in vitro FSH bioassay suitable for exploring this mechanism, we expressed hFSH-R complementary DNA in COS-7 cells and stimulated them with recombinant hTSH (rec-hTSH). Rec-hTSH elicited a dose-dependent cAMP response in the in vitro hFSH-R bioassay; however, the concentration of rec-hTSH required for half-maximal stimulation was several logs greater than that of hFSH. Rec-hTSH acted as a competitive inhibitor of hFSH at the hFSH-R, indicating that hTSH and hFSH are acting through the same receptor, namely the hFSH-R. This provides a potential novel mechanism for the precocious puberty of juvenile hypothyroidism.

Biological Assay↗

PubMed1995

The use of human recombinant gonadotropin receptors to search for immunoglobulin G-mediated premature ovarian failure.

Anti-FSH receptor antibodies, detected using animal systems, have been reported in a few patients with premature ovarian failure (POF). However, assays based on animal receptors may be inappropriate for detecting inhibiting antibodies in humans. Accordingly, we tested for interfering antibodies in patients with POF using a recombinant system expressing human (h) FSH and LH receptors. A mouse adrenal cell line transfected with the hFSH receptor (Y1-hFSHR) exhibits a dose-dependent increase in progesterone when exposed to hFSH. An embryonal kidney cell line transfected with the hLH receptor gene (hLHR-293) exhibits a dose-dependent increase in cAMP when exposed to hLH. We isolated immunoglobulins G (IgG) from 38 patients with POF and 14 normal women. We stimulated Y1-hFSHR and hLHR-293 cells with hFSH or hLH in the presence of these IgG and determined the resulting progesterone or cAMP response. The progesterone and cAMP responses obtained in the presence of IgG from patients with POF did not differ significantly from the responses in the presence of IgG from normal women. In contrast, antigonadotropin polyclonal antibodies isolated in the same manner as the above IgGs caused a greater than 90% reduction in the response of the Y1-hFSHR and hLHR-293 cells. We did not detect inhibitory antibodies in any of our 38 patients with POF. Therefore, if blocking antibodies interfering with gonadotropin-receptor interaction are a mechanism for POF, they account for a small minority of cases (< 8%).

Adolescent↗

PubMed1995

Differential effects of 2,4-dithiobiuret on the synthesis and release of acetylcholine and dopamine from rat pheochromocytoma (PC12) cells.

Chronic administration of 2,4-dithiobiuret (DTB), causes delayed-onset neuromuscular weakness in rats. This effect results from inhibition of quantal release of acetylcholine (ACh) from motor nerve terminals. The effects of noncholinergic neurotransmission are unknown. The purpose of the present study was to examine the presynaptic mechanisms involved in DTB-induced inhibition of ACh release, particularly, the specificity of action of DTB for cholinergic secretion. Differentiated pheochromocytoma (PC12) cells were used to compare the effects of DTB on the content and release of ACh and dopamine (DA) using neurochemical techniques. At concentrations of 50 to 1000 microM, DTB had little or no effect on [3H]choline uptake or on the spontaneous release of endogenous or [3H]ACh, but caused a significant decrease in release of endogenous or [3H]ACh elicited by depolarization with elevated extracellular [K+]. DTB reduced evoked release of ACh without altering cellular levels of ACh or choline, suggesting that DTB acts directly on mechanisms involved in ACh release. These alterations occurred without prominent alterations in [Ca2+]i as measured by fluorescence microscopy of individual PC12 cells loaded with fura-2. Moreover, DTB did not affect the increase of [Ca2+]i of PC12 cells in response to KCl-induced depolarization. alpha-Latrotoxin-stimulated release of ACh was not inhibited by DTB. DTB-induced suppression of depolarization-evoked release of [3H]ACh was associated with an increased level of [3H]ACh in the vesicular pool although the cytosolic pool was unaffected. High concentrations of DTB also reduced depolarization-evoked release of DA and inhibited DA synthesis resulting in a decrease in the readily releasable pool of DA. These effects occurred at higher concentrations and after longer exposures to DTB than were necessary to alter ACh release. Inasmuch as DA synthesis in the PC12 cell has been shown to be modulated by ACh release, this effect on DA release may reflect a consequence of the diminished release of ACh. These results suggest that DTB alters the release of ACh by interrupting either the mobilization and/or release of the vesicular pool of ACh.

Acetylcholine↗

PubMed1994

Molecular and cytogenetic studies of an X;autosome translocation in a patient with premature ovarian failure and review of the literature.

We have identified a patient with premature ovarian failure (POF) and a balanced X;autosome translocation: 46,X,t(X;6)(q13.3 or q21;p12) using high-resolution cytogenetic analysis and FISH. BrdU analysis showed that her normal X was late-replicating and translocated X earlier-replicating which is typical of balanced X;autosome rearrangements. Molecular studies were done to characterize the breakpoint on Xq and to determine the parental origin. PCR probes of tetranucleotide and dinucleotide repeat polymorphisms, and genomic probes were used to study DNA from the patient, her chromosomally normal parents and brother, and somatic cell hybrids containing each translocation chromosome. The translocation is paternally derived and is localized to Xq13.3-proximal Xq21.1, between PGK1 and DXS447 loci, a distance of 0.1 centimorgans. A "critical region" for normal ovarian function has been proposed for Xq13-q26 [Sarto et al., Am J Hum Genet 25:262-270, 1973; Phelan et al., Am J Obstet Gynecol 129:607-613, 1977; Summitt et al., BD:OAS XIV(6C):219-247, 1978] based on cytogenetic and clinical studies of patients with X;autosome translocations. Few cases have had molecular characterization of the breakpoints to further define the region. While translocations in the region may lead to ovarian dysfunction by disrupting normal meiosis or by a position effect, two recent reports of patients with premature ovarian failure and Xq deletions suggest that there is a gene (POF1) localized to Xq21.3-q27 [Krauss et al., N Engl J Med 317:125-131, 1987; Davies et al., Cytogenet Cell Genet 58:853-966, 1991] or within Xq26.1-q27 [Tharapel et al., Am J Hum Genet 52:463-471, 1993] responsible for POF.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1994

Subarachnoid hemorrhage and hormonal factors in women. A population-based case-control study.

OBJECTIVE: To determine the degree to which endogenous and exogenous hormonal factors influence the risk for subarachnoid hemorrhage in women. DESIGN: A population-based case-control study. SETTING: King County, Washington. PARTICIPANTS: 103 women with an incident, spontaneous subarachnoid hemorrhage and 2 age- and sex-matched controls per case-patient who were identified through random-digit dialing. MEASUREMENTS: Information on exposures was collected during in-person interviews of case-patients, controls, and their surrogates. RESULTS: Premenopausal women, especially those without a history of smoking or hypertension, were at a reduced risk for subarachnoid hemorrhage compared with age-matched postmenopausal women (odds ratio, 0.24; 95% CI, 0.09 to 0.68). The use of hormone replacement therapy was associated with a reduced risk (odds ratio, 0.47; CI, 0.26 to 0.86); the reduction was significantly greater in women who had smoked than in those that had never smoked. Of the 23 premenopausal case-patients, 74% were either menstruating when hemorrhaging occurred or had had their last menstrual period 21 or more days before hemorrhaging compared with the expected 43% (difference, 31%; CI, 4% to 58%). CONCLUSIONS: Premenopausal women are at reduced risk for subarachnoid hemorrhage, especially those without a history of smoking or hypertension. Hormone replacement therapy reduced the risk only in postmenopausal women who had ever smoked. Among women still menstruating, the risk for hemorrhage was greatest in the perimenstrual period.

Adult↗

PubMed1994

A controlled study of danazol for the treatment of karyotypically normal spontaneous premature ovarian failure.

OBJECTIVE: To determine if the immunomodulatory and gonadotropin-suppressing properties of danazol would improve follicle function or ovulation rates in patients with karyotypically normal spontaneous premature ovarian failure. DESIGN: Prospective, double-blind, crossover trial. SETTING: Tertiary care research institution. INTERVENTIONS: Two intervention phases lasting 4 months each: one phase during which patients received a standardized estrogen and progestin replacement regimen and one phase during which each patient received a twice daily 400 mg oral dose of danazol. PATIENTS: Fifty-two patients with karyotypically normal spontaneous premature ovarian failure ranging in age from 21 to 39 years. MAIN OUTCOME MEASURES: We measured serum E2 and P levels weekly during the 2 months after each intervention. We defined a serum E2 > 50 pg/mL (184 pmol/L) as evidence of ovarian follicle function and a P > 3.0 ng/mL (9.5 nmol/L) as evidence for ovulation. RESULTS: Of the 46 patients who completed the study, danazol did not significantly enhance ovarian follicle function or the chance of ovulation. Eight patients ovulated after danazol and four patients ovulated after estrogen and progestin. The power to detect a 30% and a 5% ovulation success rate with therapy was 0.80 and 0.90, respectively. Overall, 30 of 46 women (65%) demonstrated ovarian follicle function and 10 women (21%) ovulated. CONCLUSION: We were unable to demonstrate a statistically significant benefit from the immunomodulatory and gonadotropin-suppressing effects of danazol in patients with karyotypically normal spontaneous premature ovarian failure. These patients often have spontaneous remission. Thus, controlled studies are required to determine the effectiveness of treatments for this condition.

Adult↗

PubMed1994

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↗