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Biomedical subjects

A Sommer

Publications and source records attributed to A Sommer.

At least 55 records · Page 3Linked to original sources

A silastic positioner for a modiolus-hugging position of intracochlear electrodes: electrophysiologic effects.

HYPOTHESIS: It was postulated that an electrode array that achieved a close modiolar proximity would result in reduced threshold levels and amplitude slopes, as measured with electrically evoked auditory brainstem responses (EABRs). BACKGROUND: Quality and quantity of auditory information transmitted by a cochlear implant to patients with sensorineural hearing loss depend on spatial and temporal resolution achieved by the electrical intracochlear stimulation. METHODS: To improve spatial resolution, a new electrode system was developed by Advanced Bionics Corp., with the intention of obtaining greater modiolar proximity. The implant version specified for animal experiments consists of a straight electrode array of seven embedded platinum discs and a so-called Silastic-positioner. The Silastic positioner is shaped to follow the dimensions of the scala tympani with a concave (triangular) inner side, which fits the form of the electrode array. The aim of the study was to evaluate the influence of a modiolus-hugging electrode position in contrast to a conventional electrode position on EABR in short-term animal experiments. Short-term electrophysiologic studies were performed on six adult cats. After local intracochlear application of neomycin solution (50 mg/mL), electrodes were inserted into the scala tympani. Electrically evoked auditory brainstem response threshold levels and EABR amplitude slopes were systematically investigated with and without the positioner. RESULTS: Electrically evoked auditory brainstem response measurements revealed a distinct apicobasal threshold shift, with increasing thresholds toward the basal end of the electrode. After insertion of the positioner, this shift diminished or was inverted and EABR thresholds and amplitude slopes were reduced significantly. CONCLUSIONS: Threshold and amplitude slope data emphasize the functional benefit of the positioner system, especially for the stimulation of electrodes in the more basal channels.

Animals↗

Maternal low-dose vitamin A or beta-carotene supplementation has no effect on fetal loss and early infant mortality: a randomized cluster trial in Nepal.

BACKGROUND: The effect of vitamin A supplementation on the survival of infants aged <6 mo is unclear. Because most infant deaths occur in the first few month of life, maternal supplementation may improve infant survival. OBJECTIVES: The objective was to assess the effect of maternal vitamin A or beta-carotene supplementation on fetal loss and survival of infants <6 mo of age. DESIGN: Married women of reproductive age in 270 wards of Sarlahi district, Nepal, were eligible to participate. Wards were randomly assigned to have women receive weekly doses of 7000 microg retinol equivalents as retinyl palmitate (vitamin A), 42 mg all-trans-beta-carotene, or placebo. Pregnancies were followed until miscarriage, stillbirth, maternal death, or live birth of one or more infants, who were followed through 24 wk of age. RESULTS: A total of 43559 women were enrolled; 15832 contributed 17373 pregnancies and 15987 live born infants to the trial. The rate of fetal loss was 92.0/1000 pregnancies in the placebo group, comparable with rates in the vitamin A and beta-carotene groups, which had relative risks of 1.06 (95% CI: 0.91, 1.25) and 1.03 (95% CI: 0.87, 1.19), respectively. The 24-wk mortality rate was 70.8/1000 live births in the placebo group, comparable with rates in the vitamin A and beta-carotene groups, which had relative risks of 1.05 (95% CI: 0.87, 1.25) and 1.03 (95% CI: 0.86, 1.22), respectively. CONCLUSIONS: Small weekly doses of vitamin A or beta-carotene given to women before conception, during pregnancy, and through 24 wk postpartum did not improve fetal or early infant survival in Nepal.

Adult↗

Hyporetinolemia and acute phase proteins in children with and without xerophthalmia.

BACKGROUND: The relations among hyporetinolemia, acute phase proteins, and vitamin A status in children are unclear. OBJECTIVE: The objective was to examine the relations between acute phase proteins and plasma retinol concentrations in children with and without clinical vitamin A deficiency (Bitot spots and night blindness). DESIGN: The study was a nonconcurrent analysis of acute phase protein concentrations and other data from a previous clinical trial. Preschool children, 3-6 y of age, with (n = 118) and without (n = 118) xerophthalmia were assigned to receive oral vitamin A (60 mg retinol equivalent) or placebo and were seen at 5 wk. All children received oral vitamin A (60 mg retinol equivalent) at 5 wk. RESULTS: At baseline, alpha(1)-acid glycoprotein (AGP) was elevated in 42.9% and 23.5% (P < 0.003) and C-reactive protein (CRP) was elevated in 17.7% and 13.7% (NS) of children with and without xerophthalmia, respectively. Hyporetinolemia (retinol < 0.7 micromol/L) occurred in 61.0% and 47.4% (P < 0.04) of children with and without xerophthalmia, respectively. A history of fever, a history of cough, and nasal discharge noted on examination were each associated with elevated acute phase proteins. Vitamin A supplementation increased plasma retinol at 5 wk but had no significant effect on concentrations of acute phase proteins. CONCLUSIONS: Elevated acute phase protein concentrations and infectious disease morbidity are closely associated during vitamin A deficiency.

Acute-Phase Proteins↗

The combination of insulin-like growth factor I and insulin-like growth factor-binding protein-3 reduces insulin requirements in insulin-dependent type 1 diabetes: evidence for in vivo biological activity.

Insulin-like growth factor-I (IGF-I) enhances insulin action in normal subjects and in patients with both type 1 and 2 diabetes; however, its administration is associated with significant side effects in a high percentage of patients. The coadministration of IGF binding protein-3 (IGFBP-3, the predominant IGF binding protein in serum) with IGF-I limits IGF-I inducible side effects, but it does not attenuate the ability of IGF-I to enhance protein synthesis and bone accretion; therefore, we determined whether IGF-I/IGFBP-3 would retain biological activity in type 1 DM and limit side effects associated with free IGF-I administration. Twelve patients received recombinant human IGF-I plus IGFBP-3 (2 mg/kg-day) by continuous sc infusion for 2 weeks. Each subject served as his own control; and, during a paired 2-week period, each received a placebo infusion. The order of the treatments was randomized. Subjects were placed on a constant caloric intake but were allowed to adjust insulin doses to maintain appropriate levels of glycemic control. Subjects measured blood glucose four times per day at home and kept a log of their insulin use. Frequent sampling for glucose, insulin, and GH was conducted during four inpatient study periods, one at the beginning and one at the end of each 2-week study interval. During IGF-I/IGFBP-3, insulin doses were reduced by 49%, and mean serum glucose was reduced by 23%. Free insulin levels obtained during frequent sampling in hospital fell 47% on IGF-I/IGFBP-3, compared with control, but showed no change with placebo. Concomitant glucose measurements did not differ in the two treatment groups. There was no change in body weight. Fructosamine levels decreased by 12%, but this was not significant (P < 0.1). Fasting triglyceride was unchanged, but cholesterol declined from 170 +/- 24 to 149 +/- 31 mg/dL (P < 0.05). IGFBP-2 (an IGF-I-dependent responsive variable) rose from 141 +/- 56 to 251 +/- 98 ng/mL (P < 0.01) on IGF-I/IGFBP-3. To analyze the mechanism by which IGF-I/IGFBP-3 might reduce insulin requirements, the change in serum GH was quantified. Mean GH levels were reduced by 72%, from 2.48 to 0.55 ng/mL (P < 0.001). An equal number (40%) of drug- and placebo-treated subjects had minor hypoglycemic episodes at home that required adjustment of insulin doses. No episode was classified as severe. In contrast to previous studies with free IGF-I, there were no cases of edema, headache, jaw pain, retinal edema, or Bell's palsy. No subject withdrew because of drug complications. These findings indicate that IGF-I/IGFBP-3 is biologically active on carbohydrate metabolism, as measured by a decrease in insulin requirements in patients with type 1 diabetes. Further studies will be required to determine the long-term safety and efficacy of this combination in patients with insulin resistance and diabetes.

Adult↗

Restructuring French hospitals. Some problems and some solutions.

Hospitals are the sick component of the healthcare sector in many European countries and have been so for a long time. As long as 10 years ago, economists noted the urgent need for hospitals to restructure. During the last 5 years, there has been a surge in hospital mergers, closures and revamping throughout France. Yet, the results have been mixed. The number of hospital beds is down, but expenses are not, and new demands for services are not being met. Why are there still problems? It is because there are still significant socio-political, conceptual, and financial obstacles to successful restructuring. Consideration by the author of a case study in which would-be competitors achieve a win-win restructuring illustrates the conditions that must be addressed for there to be a chance of success.

France↗

Analysis of the Max-binding protein MNT in human medulloblastomas.

Medulloblastomas (MBs) are the most frequent malignant brain tumors in children. The molecular pathogenesis of these tumors is still poorly understood. Microsatellite and restriction-fragment-length polymorphism studies have revealed allelic loss of genetic material on the short arm of chromosome 17 in the region 17p13 in approximately 50% of MBs, suggesting the presence of a tumor-suppressor gene in this region. A candidate for this putative tumor-suppressor is the MNT gene, located at 17p13.3 and encoding a Max-interacting nuclear protein with transcriptional-repressor activity. In this study, we analyzed MNT mRNA and protein expression in 44 MB samples, including 32 primary tumors, 3 recurrent tumors and 9 MB cell lines. Allelic loss at 17p13.3 was found in 49% of informative cases. RT-PCR showed MNT mRNA expression in all cases analyzed. Endogenous Mnt protein with an apparent molecular weight of 72 to 74 kDa was detected in lysates from MB cell lines. The presence and functional integrity of Mnt in MBs were tested in electrophoretic mobility-shift assays. These experiments demonstrated that Mnt interacts with Max, and that this heterodimer binds DNA specifically, suggesting a functional bHLHZip domain of MB-derived Mnt. In support, single-strand conformation-polymorphism (SSCP) analyses revealed no mutation in the bHLHZip region. Deletion of the Mnt Sin3 interaction domain was shown to convert Mnt from an inhibitor of myc/ras-co-transformation into a molecule capable of cooperating with Ras in transformation. This region therefore was screened for mutation by SSCP: again, no alterations were found. These findings indicate that the MNT gene located at 17p13.3 is not likely to be involved in the molecular pathogenesis of MBs.

Basic Helix-Loop-Helix Leucine Zipper Transcriptio↗

Double blind, cluster randomised trial of low dose supplementation with vitamin A or beta carotene on mortality related to pregnancy in Nepal. The NNIPS-2 Study Group.

OBJECTIVE: To assess the impact on mortality related to pregnancy of supplementing women of reproductive age each week with a recommended dietary allowance of vitamin A, either preformed or as beta carotene. DESIGN: Double blind, cluster randomised, placebo controlled field trial. SETTING: Rural southeast central plains of Nepal (Sarlahi district). SUBJECTS: 44 646 married women, of whom 20 119 became pregnant 22 189 times. INTERVENTION: 270 wards randomised to 3 groups of 90 each for women to receive weekly a single oral supplement of placebo, vitamin A (7000 micrograms retinol equivalents) or beta carotene (42 mg, or 7000 micrograms retinol equivalents) for over 31/2 years. MAIN OUTCOME MEASURES: All cause mortality in women during pregnancy up to 12 weeks post partum (pregnancy related mortality) and mortality during pregnancy to 6 weeks postpartum, excluding deaths apparently related to injury (maternal mortality). RESULTS: Mortality related to pregnancy in the placebo, vitamin A, and beta carotene groups was 704, 426, and 361 deaths per 100 000 pregnancies, yielding relative risks (95% confidence intervals) of 0. 60 (0.37 to 0.97) and 0.51 (0.30 to 0.86). This represented reductions of 40% (P<0.04) and 49% (P<0.01) among those who received vitamin A and beta carotene. Combined, vitamin A or beta carotene lowered mortality by 44% (0.56 (0.37 to 0.84), P<0.005) and reduced the maternal mortality ratio from 645 to 385 deaths per 100 000 live births, or by 40% (P<0.02). Differences in cause of death could not be reliably distinguished between supplemented and placebo groups. CONCLUSION: Supplementation of women with either vitamin A or beta carotene at recommended dietary amounts during childbearing years can lower mortality related to pregnancy in rural, undernourished populations of south Asia.

Administration, Oral↗

[Echo-planar diffusion-weighted MRI in the diagnosis of acute ischemic stroke: characterisation of tissue abnormalities and limitations in the interpretation of imaging findings].

INTRODUCTION: An accurate diagnosis is frequently difficult in early stroke. Diffusion-weighted (DW) magnetic resonance imaging (MRI) allows visualization of ischemic parenchyma and quantitative assessment of tissue changes before unequivocal abnormalities appear on T(2)-weighted MRI. METHODS: We analyzed 105 MRI examinations of patients with acute stroke (<24 h) with regard to patterns of abnormalities in T(2)-weighted and DW MRI. Furthermore we assessed the influence of artifacts related to DW echo-planar single-shot MRI on image interpretation. RESULTS: Depending on the time of patient assessment there were three partly overlapping T(2)/DW patterns: (1) in the very early phase (</=1.5 h after symptom onset) there was no T(2) abnormality and no definite abnormality of diffusion; (2) no T(2) abnormality and restricted diffusion (1.5-4 h); (3) T(2) hyperintensity and restricted diffusion (>/=3 h). Typical artifacts (susceptibility distortions, N/2 artifact, chemical shift artifact and eddy currents artifact) had to be considered when interpreting images. CONCLUSIONS: Provided typical artifacts are taken into consideration, echo-planar DW MRI allows a more precise diagnostic assessment in acute stroke.

Acute Disease↗

Primary sequence of a putative non-ATPase subunit of the 26S proteasome from Entamoeba histolytica is similar to the human and yeast S2 subunit.

The cDNA coding for a non-ATPase S2 subunit of the 26S proteasome from Entamoeba histolytica was cloned from a cDNA library (EhS2). The open reading frame has 2529 bp and the deduced amino acid sequence encodes a protein with a calculated molecular mass of 92,000 Da. EhS2 has 29-35% identity with the three other known S2 subunit sequences of yeasts and humans.

Amino Acid Sequence↗

Health, medicine, and ophthalmology: facing the facts and paying the piper LVI Edward Jackson Memorial Lecture.

PURPOSE: To describe the sources of tension within the health care system and methods for pursuing their solution. METHODS: Presentation of observations pertinent to patient, provider, and payer perspectives relevant to the cost, delivery, and quality of care and their impact on health. RESULTS: Societal forces, not just wealth, are major determinants of both health and the costs of health care. CONCLUSIONS: Tensions created by rising health care costs in the face of finite societal resources will increase in the years ahead. These can be resolved only by realizing new efficiencies in care, and prioritizing, through an explicit process, the care that is to be provided.

Cost Control↗

Morphological and functional development of the rumen in the calf: influence of the time of weaning. 1. Morphological development of rumen mucosa.

The objective of this study was to determine whether the nutritional regimen of rearing calves would influence the morphometric and histological development of rumen mucosa. Twelve male Holstein calves 7 d of age were assigned to three groups of 4 animals each: milk group (I), early weaned (6 weeks) group (II) and late weaned (9 weeks) group (III). All animals received additional solid feed. Animals of group I were slaughtered after 6 weeks of age, whereas those in groups II and III were slaughtered after 9 weeks of age. At slaughter, the ruminal digesta amounted to 2035 g (milk group), 3092 g (late weaned group) and 5374 g (early weaned group). The differences in the ruminal molar percentage of SCFA were not significant. There was a trend for lower pH and higher SCFA concentrations in the order late weaned, early weaned and milk fed animals (pH: 6.4, 6.6 and 6.7, respectively; SCFA: 96, 87 and 77 mmol/l, respectively). The mean length (1.07 mm in milk group, 1.45 mm in late weaned group and 1.87 mm in early weaned group), width (0.43, 0.58 and 0.71 mm, respectively) and surface of papillae (190, 232 and 241 mm2/cm2 mucosa, respectively) increased with both the age of the animals and the elevated intake of solid feed, whereas the number of papillae (210, 140 and 92 per cm2 mucosa, respectively) decreased. In both milk-fed groups type A and B corneal cells were present in the Stratum corneum, whereas in the earlier weaned calves type C-cells could be also seen. These findings indicate a more advanced stage of development of the rumen epithelium in the earlier weaned calves fed higher amounts of concentrate and hay.

Animal Feed↗

Clinical range and MRI in Creutzfeldt-Jakob disease with heterozygosity at codon 129 and prion protein type 2.

A 68 year old woman with sporadic Creutzfeldt-Jakob disease is described, who neither showed characteristic EEG abnormalities nor a positive test of the neuronal protein 14-3-3 or neuron specific enolase (NSE) in CSF, despite a clinical presentation with ataxia of cerebellar type, rapidly progressive dementia, myoclonus, and marked hyperintense signal abnormalities in the deep cortical layers and the basal ganglia on T2 and diffusion weighted MRI. Moreover she showed atypical clinical features with a syndrome of inappropriate antidiuretic hormone (ADH) secretion (SIADH) and a peripheral sensorimotor polyneuropathy. Whether these disturbances are independent of Creutzfeldt-Jakob disease or a feature of it is discussed. It has recently been shown that in Creutzfeldt-Jakob disease different clinical and pathological phenotypes correlate with the polymorphism at codon 129 of the prion protein gene (PRNP) and the type of the protease resistant fragment that accumulates in the brain. According to the new classification at least six sporadic variants of Creutzfeldt-Jakob disease exist. The molecular genetic analysis showed heterozygosity of PRNP at codon 129 for methionine and valine and the presence of PrP(CJD) type 2 in the brain of this patient. As a new feature of changes on MRI, striking cortical changes of hyperintense signals are described in diffusion weighted as well as T2 weighted MRI that directly correlate with the histomorphological spongy degeneration of the brain in this region. In cases of rapidly progressive dementia, Creutzfeldt-Jakob disease always needs to be considered even if unusual features are present and current diagnostic criteria are not in favour of this disease.

Aged↗