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Biomedical subjects

L Nelson

Publications and source records attributed to L Nelson.

At least 37 records · Page 2Linked to original sources

Myotonic dystrophy is a significant cause of idiopathic polyhydramnios.

OBJECTIVE: Myotonic dystrophy, the most common form of muscular dystrophy seen in pregnant women, may be a significant cause of middle trimester polyhydramnios. Our purpose was to determine the prevalence of myotonic dystrophy in women with idiopathic polyhydramnios and to characterize the ultrasonographic findings associated with cases. STUDY DESIGN: We examined the cases of 67 patients who were delivered of infants at the University of Utah between 1992 and 1996 with a diagnosis of idiopathic polyhydramnios (amniotic fluid index >25). Women with diabetes mellitus, hydrops, or fetal anomalies known to cause polyhydramnios were excluded from the study. Amniotic fluid samples or cord blood samples were obtained from 41 patients, and polymerase chain reaction amplification and Southern blot analysis were performed to detect the presence of the myotonic dystrophy mutation. Ultrasonographic findings, prenatal course, and neonatal outcomes were reviewed in all cases. RESULTS: Four of the 41 patients tested had the myotonic dystrophy mutation, yielding a prevalence in our population of 9.7%. Three of the 4 patients reported a family history of myotonic dystrophy. Ultrasonographic findings associated with a positive result included abnormal posturing of extremities (3/4) and unilateral clubbed foot (3/4). No other structural or growth abnormalities were seen. Two of the patients were delivered before term, 1 at 26 weeks and 1 at 32 weeks. Three of the 4 infants were severely affected, necessitating admission to the intensive care unit, and 1 died on day 11 after birth. One infant, whose myotonic dystrophy mutation consisted of between 800 and 900 triplet repeats, did not require admission to the intensive care unit. CONCLUSION: Myotonic dystrophy may be seen as idiopathic polyhydramnios and should be considered as part of the differential diagnosis in these cases. Women with a familial history of myotonic dystrophy or ultrasonographic evidence of hypotonia, including positional abnormalities of the extremities, should be offered deoxyribonucleic acid testing for the myotonic dystrophy mutation.

Congenital Abnormalities↗

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Community Health Services↗

Factor V Leiden is not common in patients diagnosed with primary pulmonary hypertension.

Substantial evidence suggests that thrombosis contributes to the pathogenesis of primary pulmonary hypertension (PPH). An abnormal factor V (factor V Leiden) may contribute to thrombosis in the pulmonary microcirculation of PPH patients. A point mutation in which adenine is substituted for guanine at nucleotide 1691 (1691A) alters factor V so that it resists cleavage by activated protein C. Heterozygosity for the 1691A mutation is more common (2-8%) in Caucasian Europeans and Americans than in Africans (1%) and Asians (<1%). The aim of the study was to examine the prevalence of the mutation that codes for factor V Leiden in individuals with PPH. We identified 42 Caucasians diagnosed with PPH. We extracted deoxyribonucleic acid (DNA) from whole blood and assayed DNA samples for the point mutation (1691 A) that codes for factor V Leiden. One out of 42 (2.4%; 95% confidence interval=0.1-12.6) Caucasians diagnosed with PPH was heterozygous for the normal 1691G and mutant 1691A allele. All 10 individuals with familial PPH were homozygous for the normal 1691G allele. The prevalence of heterozygosity for the 1691A allele and the normal 1691G allele does not differ from that observed in reference (control) populations. The low prevalence of the 1691A mutation among individuals diagnosed with primary pulmonary hypertension provides evidence that factor V Leiden does not contribute to the pathogenesis of the disease in most patients.

Adult↗

Analysis of prenatal and gestational care given to women with epilepsy.

OBJECTIVE: To assess past care practices of neurologists and obstetricians to identify areas in which practice patterns differ from currently accepted optimal care. METHODS: Retrospective chart review of 155 women identified as having a diagnosis of epilepsy (or seizure disorder) who had been pregnant any time between January 1988 and December 1995 and were admitted to Stanford University Hospital for delivery. A total of 161 pregnancies (132 women) were selected for study. RESULTS: An obstetrician was seen at some point during the pregnancy in 99% of the pregnancies, whereas a neurologist was seen at least once in only 64% of the pregnancies. In the 3 months before conception, an obstetrician was seen in 5% of the pregnancies and a neurologist was seen in 15%. Seventy-five percent of the patients taking antiepileptic medication and 65% of the untreated patients had documentation of folate supplementation at any time during pregnancy. Vitamin K supplementation in the final month of pregnancy was documented for only 41% of those receiving antiepileptic drugs. In over one-third of the pregnancies the mother did not have a maternal serum alpha-fetoprotein measure documented and a similar percentage did not receive genetic counseling. Monitoring of the maternal serum concentration of the non-protein-bound fraction of the prescribed antiepileptic drugs was not documented. CONCLUSIONS: We identified specific omissions of appropriate vitamin supplementation, genetic counseling, and drug level monitoring. Educational efforts should be targeted to improve the management of pregnancy in women with epilepsy.

Abortion, Induced↗

The spread of state any willing provider laws.

OBJECTIVE: To describe the growth of any willing provider (AWP) and freedom of choice (FOC) laws applicable to managed care firms and to explore empirically the determinants of their enactment. STUDY SETTING: A 1996 compendium of state laws and state-level data from the 1991-1994 period. STUDY DESIGN: Pooled cross-section time-series logistic regression of the decision to enact various types of AWP and FOC laws. Analysis uses a public choice framework to examine enactment. Key variables include proxy measures of proponent and opponent strength and the political environment. PRINCIPAL FINDINGS: The model works well for laws affecting hospitals, but performs poorly for physician and pharmacy laws. More providers are associated with the enactment of AWP and FOC laws. More large employers are associated with a reduced likelihood of enactment of some forms of the laws but not others. Conservative states are more likely to enact laws limiting selective contracting with hospitals and physicians. States with greater interparty competition are also more likely to adopt some types of legislation. CONCLUSIONS: The empirical results generally are consistent with the view that AWP and FOC laws are often enacted as a defensive strategy on the part of providers, but additional research is needed to provide a more definitive assessment of the determinants of these laws. Suggestions for future research are provided.

Decision Support Techniques↗

Angiotensinogen T235 expression is elevated in decidual spiral arteries.

Preeclampsia is associated with a common molecular variant of angiotensinogen (Met235Thr). This variant is in tight linkage disequilibrium with a mutation in the angiotensinogen promoter, G(-6)A, which leads to elevated expression in vitro. Since angiotensin II levels could play a role in atherotic changes of the uterine spiral arteries associated with preeclampsia, we investigated angiotensinogen expression in the first trimester uterus. We localized angiotensinogen transcription in uterine decidua using in situ reverse transcription PCR. We then compared decidual T235 expression levels to M235 levels in heterozygous women using an allele-specific ligation assay and a single nucleotide primer extension assay. In human decidua, angiotensinogen is expressed only in spiral artery smooth muscle cells. Heterozygous women have significantly elevated expression of the T235 allele compared to the M235 allele (P < 0.0001). These observations suggest that elevated expression of the T235 allele in decidual spiral arteries may cause first trimester atherotic changes leading to preeclampsia.

Alleles↗

Leukodystrophy in patients with ovarian dysgenesis.

We describe clinical, biochemical, pathological, and spectroscopic findings in 4 women, aged 15 to 29 years, from three unrelated families who had a unique combination of a central nervous system white matter disease and primary ovarian failure. All had normal initial development but 3 had borderline low IQ and academic difficulties in primary school. Puberty did not develop in 2 patients and was arrested in a third patient. The fourth patient had premature ovarian failure at the age of 13 years. Head magnetic resonance imaging showed diffuse white matter disease, with frontal cortical atrophy in the most clinically advanced patient. All patients had normal karyotype and normal findings on extensive evaluations for known leukodystrophies, for other metabolic diseases, and for causes of ovarian failure. Proton magnetic resonance spectroscopic imaging showed reduction of choline-containing compounds in the affected white matter in all patients and reduction of N-acetylaspartate in the unaffected frontal white matter of 2 patients. All patients had evidence of primary gonadal insufficiency with a normal hypothalamic-hypophyseal axis. Pathological analysis showed streak ovaries in 1 patient and signs of hypomyelination, and gliosis on brain biopsy in another patient. In conclusion, we present a novel group of patients who have in common leukodystrophy, primary ovarian dysfunction, and magnetic resonance spectroscopic abnormalities.

Adolescent↗

Hypothalamic-pituitary-adrenal activation by the bacterial superantigen staphylococcal enterotoxin B: role of macrophages and T cells.

Staphylococcal enterotoxin B (SEB) is a bacterial superantigen which stimulates T cells bearing the V beta 8 motif on the T-cell receptor. This stimulation is MHC class II dependent, and in vivo results in a rapid and pronounced T-cell cytokine response. Based on previous evidence that SEB stimulates corticosterone production in BALB/c mice, which possess a high percentage of V beta 8+ T cells, we explored the effects of SEB on the hypothalamic-pituitary-adrenal (HPA) axis and identified the peripheral immunologic cellular requirements for these effects. Administration of SEB stimulates corticosterone in a dose-dependent manner, with peak production of corticosterone occurring by 2 h after intraperitoneal challenge with 50 micrograms SEB. Challenge with staphylococcal enterotoxin A, which activates V beta 3+ and V beta 11+ T cells (deleted during ontogenesis in BALB/c mice), did not increase ACTH or corticosterone production. Furthermore, SEB challenge increased plasma ACTH, which accounted for the increased plasma corticosterone, and increased the expression of c-fos in the PVN region of the hypothalamus. In vivo elimination of macrophages did not prevent the corticosterone response to SEB, suggesting that pituitary-adrenal activation does not require macrophages. However, when mice were pretreated with the T-cell immunosuppressant cyclosporin A, the significantly increased ACTH and corticosterone production in response to SEB was dramatically attenuated. These results demonstrate that bacterial superantigens can stimulate the HPA axis, and that functional T cells may play an obligatory role in this effect.

Adrenal Glands↗

Different excitation-contraction coupling mechanisms exist in squid, cuttlefish and octopod mantle muscle

Excitation-contraction (EC) coupling was studied in central zone mantle muscle fibres of a squid (Alloteuthis subulata), a cuttlefish (Sepia officinalis) and an octopod (Eledone cirrhosa). Thin slices of muscle were used for twitch experiments and enzymatic isolation of single fibres for whole-cell patch-clamp studies. The current required for a supramaximal twitch response during direct stimulation of muscle slices was lower for squid than for cuttlefish. In squid, but not in cuttlefish, the current-response relationship was independent of slice thickness (range 0.1-0.5 mm). Twitches of squid and cuttlefish slices were reversibly abolished by removal of extracellular Ca2+. In squid, but not in cuttlefish, the current-response relationship was Na+-dependent, and in the absence of Na+ higher current strengths were required to generate a supramaximal response. In whole-cell voltage-clamp experiments on isolated muscle fibres from squid, cuttlefish and Eledone cirrhosa, a sustained inward current was recorded upon depolarisation. This current was blocked by 5 mmol l-1 Co2+ and suppressed by 10 micromol l-1 nifedipine. In squid, an additional inward fast-activating transient current was seen which was blocked by 2 micromol l-1 tetrodotoxin and depolarised holding potentials. The fast current represents a voltage-activated Na+ channel, and the slow currents represent L-type Ca2+ channels. We conclude that squid possess a specialised rapid EC coupling mechanism in central zone fibres that is absent in cuttlefish and Eledone cirrhosa.

Journal Article↗

The use of epidural steroid injection and manipulation on patients with chronic low back pain.

OBJECTIVES: To document the efficacy of combined epidural steroid injection (ESI) and manipulation to the lumbar spine in patients suffering from chronic low back pain (LBP). SUMMARY OF BACKGROUND DATA: The use of ESI in conjunction with lumbar manipulation has seldom been reported in the literature but has offered promising results when studied. STUDY DESIGN: Retrospective repeated-measures analysis of patients with chronic LBP who received ESIs combined with spinal manipulation. METHODS: A retrospective analysis using a repeated-measures format was performed on 17 cases of patients who had received ESI and manipulation to the lumbar spine. All patients were medically stable for chronic mechanical LBP and had experienced a suboptimal response to conventional care. The principle investigator was blinded from data outcomes when determining patient eligibility for the study. A subjective patient improvement scale was used to monitor degree of success. RESULTS: Ten of the 17 patients were eligible for the study. Patients were eliminated for lack of consistency of data collection, having received an additional procedure after conventional care, involvement of the cervical spine; one patient experienced an unrelated medical problem. After 1 yr of conventional care, the patients reported a 25.5% improvement. (Conventional care included ESI and manipulation done at separate times.) After on ESI with subsequent manipulation, these same patients reported a 50.5% improvement. Mean improvement was 25.00% (SD = 19.51, SEM 6.19, t = 4.04 and p = .0015). CONCLUSION: The use of ESI performed with manipulation seems to offer promise for a carefully selected group of patients. ESI combined with manipulation should be considered in patients who do not respond to conventional forms of care.

Adult↗

Isolation and characterization of an avian slow myosin heavy chain gene expressed during embryonic skeletal muscle fiber formation.

We have isolated and begun characterization of the quail slow myosin heavy chain (MyHC) 3 gene, the first reported avian slow MyHC gene. Expression of slow MyHC 3 in skeletal muscle is restricted to the embryonic period of development, when the fiber pattern of future fast and slow muscle is established. In embryonic hindlimb development, slow MyHC 3 gene expression coincides with slow muscle fiber formation as distinguished by slow MyHC-specific antibody staining. In addition to expression in embryonic appendicular muscle, slow MyHC 3 is expressed continuously in the atria. Transfection of slow MyHC 3 promoter-reporter constructs into embryonic myoblasts that form slow MyHC-expressing fibers identified two regions regulating expression of this gene in skeletal muscle. The proximal promoter, containing potential muscle-specific regulatory motifs, permits expression of a reporter gene in embryonic slow muscle fibers, while a distal element, located greater than 2600 base pairs upstream, further enhances expression 3-fold. The slow muscle fiber-restricted expression of slow MyHC 3 during embryonic development, and expression of slow MyHC 3 promoter-reporter constructs in embryonic muscle fibers in vitro, makes this gene a useful marker to study the mechanism establishing the slow fiber lineage in the embryo.

Amino Acid Sequence↗

Evaluation of a HIV/AIDS education program for adolescents.

The adolescent population has recently been recognized as one of the groups at risk for human immunodeficiency virus (HIV) infection. Statistics are beginning to document the extent of this trend. This study is aimed at determining adolescent sexual behaviors and the efficacy of a medical student-run acquired immune deficiency syndrome (AIDS) education program. Medical students taught 2,169 high school students in the St. Louis area with a pre- and post- intervention questionnaire administered to record levels of HIV/AIDS knowledge and sexual practices. Data revealed that 56.4% of the respondents were sexually active with 70.4% having multiple partners and 61.0% admitting to unprotected sex. These students demonstrated a significant increase in their knowledge about HIV infection after the educational program. The results show that, adolescents are sexually active and more importantly, they are practicing behaviors that put them at risk for HIV/AIDS, a risk which they recognize. Finally, the educational intervention did increase students' knowledge of HIV/AIDS. This may not translate into a change in behaviors, but it is a first step.

Adolescent↗

Rates of flow of technetium 99m--labeled human serum albumin from peripheral injection sites to sentinel lymph nodes.

BACKGROUND: The new technique of sentinel lymphadenectomy for cutaneous melanoma provided us with a unique opportunity to quantitate the rates of lymphatic flow in afferent lymphatics. METHODS: Seventeen melanoma patients underwent preoperative lymphoscintigraphy with technetium 99m-human serum albumin (HSA). The time and distance between the injection site and the sentinel lymph node (LN) were recorded. By comparison, lymphatic flow rates between footpad, popliteal LN, femoral LN, and systemic blood were measured in 60 female mice (C57BL/6) after footpad injection of 99mTc-HSA. RESULTS: The rate of lymphatic flow to 14 axillary, four inguinal, one popliteal, and one parotid sentinel LNs averaged 10.4 +/- 7.3 cm/min. In contrast, the lymphatic flow rate between the footpad and the popliteal LN in mice (analogous to the sentinel LN in human beings) averaged 1.33 +/- 0.52 cm/min. There was a marked delay in the passage of radionuclide through the popliteal LN with consequent slowing of the rate of flow between the popliteal and femoral LNs to 0.22 cm/min. CONCLUSION: Lymphatic flow to the sentinel LN occurs rapidly from both human skin and murine footpads. This information might be helpful in planning the timing of the incision after vital blue dye injection for identifying the sentinel LN.

Animals↗

Intraventricular bleeding after the use of thrombolytics in a cocaine user.

Cocaine-induced myocardial infarct is a medical emergency with increasing prevalence. The efficacy of thrombolytics in patients with cocaine-induced infarcts has not been well studied. This report describes the case of a patient who presented with presumed cocaine-induced myocardial infarct. The patient was treated with intravenous thrombolysis and developed an intraventricular bleed with herniation and death. Physicians should be aware of this grave consequence in a generally young population.

Cerebral Hemorrhage↗