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Biomedical subjects

A Sommer

Publications and source records attributed to A Sommer.

At least 235 records · Page 13Linked to original sources

On estimating efficacy from clinical trials.

We define 'biologic efficacy' as the effect of treatment for all persons who receive the therapeutic agent to which they were assigned. It measures the biologic action of treatment among compliant persons. In a randomized trial with one treatment and one placebo control, one can theoretically estimate efficacy by comparing persons who complete the treatment regimen with controls who similarly complete the control regimen. In practice, however, we make this comparison with reservation because a control protocol often presents a different challenge for compliance than does the treatment, so that the compliant subgroups are not comparable. Standard practice employs intent-to-treat comparisons in which one compares those randomized to treatment and control without reference to whether they actually received the treatment. Intent-to-treat comparisons estimate the 'programmatic effectiveness' of a treatment rather than its biologic efficacy. This paper introduces and derives the statistical properties of an alternative estimator of biologic efficacy that avoids the potential selection bias inherent in a comparison of compliant subgroups. The method applies to randomized trials with a dichotomous outcome measure, whether or not a placebo is given to the control group. The idea is to compare the compliers in the treatment group to an inferred control subgroup chosen to eliminate selection bias. The methodology was motivated by and is illustrated in the analysis of a randomized community trial of the impact of vitamin A supplementation on children's mortality.

Bias↗

National outcomes of cataract extraction. I. Retinal detachment after inpatient surgery.

Rehospitalization for retinal detachment (RD) was studied in 338,141 Medicare beneficiaries older than 65 years of age who were undergoing inpatient cataract extraction in 1984. Extracapsular cataract extraction (ECCE) was performed in 60% of patients, intracapsular cataract extraction (ICCE) in 31%, and phacoemulsification in 9%. The risk of rehospitalization for RD within 4 years of ICCE was 1.55% over 1.5 times the risk associated with ECCE (0.9%). The risk of RD after phacoemulsification was 1.17%. Cataract surgery accompanied by anterior vitrectomy was associated with a 5.0%, likelihood of RD at 4 years, which is 4.5 times greater than that for cataract surgery alone (1.12%). White patients were 1.7 times more likely to be rehospitalized for RD than were black patients (1.15% versus 0.67%; P less than 0.001). In both races, younger patients were more likely to be rehospitalized for RD than were older patients (P less than 0.001). While the increased rate of RD after ICCE versus ECCE confirms previously held clinical beliefs, the increase in the risk following phacoemulsification (P less than 0.0001) has not been reported previously.

Aged↗

Reliability of visual field results over repeated testing.

Fifty-one normal subjects, 337 with ocular hypertension, and 55 patients with glaucoma underwent C-30-2 testing on the Humphrey Field Analyzer on at least three occasions over a 6-year period. The time between tests was approximately 1 year. Using the manufacturer's standard for a reliable field (false-positive and false-negative rates, less than 33%; fixation losses, less than 20%), no trends in the proportion of reliable fields or the component indices were observed over time. Four percent of normal subjects, 9% of those with ocular hypertension, and 8% of patients with glaucoma were unable to meet the reliability standard every time they were tested. This repeated lack of reliability was due almost exclusively to fixation losses. However, patients with glaucoma were more likely to have repeatedly high false-negative responses than those with ocular hypertension or normal subjects, providing further evidence that false-negative responses are more indicative of glaucoma than of patient reliability.

Adult↗

[The value of digital imaging techniques in skeletal imaging].

The clinical value and the imaging characteristics of digital radiography systems (image intensifier (I.I.) radiography: Polytron/Siemens, storage phosphor radiography: PCR/Philipps) in skeletal imaging were compared with film-screen radiography and 100 mm technique. The influence of spatial and contrast resolution, entrance dose and detectability of lytic, osteoblastic and cortical lesions were studied as well as the images of 25 parallel examined patients. Only with the small image intensifier (diameter 14 cm) the quality of 100 mm technique and digital I.I. radiography was equivalent to storage phosphor and film-screen radiography. Storage phosphor radiography seems to be better qualified than I.I. radiography to replace conventional techniques in skeletal imaging.

Bone Neoplasms↗

[Postileal nutrient digestibility in cattle].

Four heifers of an average live weight of 301 kg supplied with ileocaecal re-entrant cannulae received rations consisting of 4 kg hay (variants A und B), 1 kg coarse wheat meal, 0.4 kg molasses, 100 g urea and 30 g mixed minerals per animal and day. After a 14-day preliminary feeding period the ileum digesta was quantitatively collected at the re-entrant cannula over 24 h. 10% of the digesta were used for analysis, the remainder was heated to 37 degrees C and returned. Under consideration of the digesta passage through the colon the 24-hour collection of faeces was started after a 6-hour delay after the first replacement of digesta. Losses of nutrients were calculated from the values analysed from digesta and faeces. No differences could be ascertained between the two hay variants. On an average of the two rations the nutrient losses of the scaffold substances-equivalent to the digestibility in the colon-showed the following values: crude fibre = 10.6%, NDF = 10.4%, ADF = 11.9% and hemicellulose = 7.4%. The losses of the other nutrients, corresponding to their apparent digestibility, had the following values: crude protein = 12.1%, crude fat = 10.7%, N-free extracts = 18.9%, ash = 31.2%, dry matter = 17.5%. The water balance showed that 8.2 l water of the 23.4 l supplied with the ileum digesta were excreted in faeces.

Animal Feed↗

Bone mass in healthy children: measurement with quantitative DXA.

Dual-energy x-ray bone densitometry was used to study the lumbar vertebral bone mass in 218 healthy children (134 girls and 84 boys) aged 1-19 years. Vertebral bone mass increased with weight, age, and pubertal Tanner stage. Results of multiple regression analyses showed that Tanner stage and weight were the best predictive indicators of bone mass and bone mineral density. The influences of age, sex, race, physical activity, and diet were not significant when Tanner stage and weight were controlled. Two tables of predictive intervals for lumbar vertebral bone mineral density in healthy children (one based on Tanner stage and weight; the other, on age and weight) are presented. With normative data now available for use with this precise technique, clinicians can better detect abnormal bone mineral density in children and evaluate changes in mineralization over time.

Absorptiometry, Photon↗

Dipolar solvent relaxation on a nanosecond time scale in ether phospholipid membranes as determined by multifrequency phase and modulation fluorometry.

The present study reports on the observation of dipolar solvent relaxation in phospholipid membranes using multifrequency phase and modulation fluorometry. We measured the time-resolved emission spectra of 6-propionyl-2-(dimethylamino)naphthalene (PRODAN) in artificial bilayer membranes of chemically defined acyl-, alkyl-, and alkenyl-substituted phospholipids at 15 degrees C. 1-Palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine, 3-O-hexadecyl-2-oleoyl-sn-glycero-1-phosphocholine, or 1-O-hexadec-1'-enyl-2-oleoyl-sn-glycero-3-phosphocholine (plasmalogen) were used as matrix lipids. The chemical structures of these lipids differ only with respect to the type of linkage (carboxyl ester, ether, or enol ether bond) between glycerol and the hydrophobic chain linked to the primary hydroxyl of glycerol. At 15 degrees C, all the lipids are in the liquid crystalline state. PRODAN probably localizes at the hydrophobic-hydrophilic interface of the phospholipid bilayer [Chong, P. L. (1988) Biochemistry 27, 399-404]. We found faster solvent relaxation of PRODAN in membranes composed of the ether lipid compared to that in the ester lipid membranes. On the other hand, the fluorescence anisotropies of the label were very similar, showing that the motion of the label itself is similar in ether and carboxyl ester lipids. We conclude that the spectral differences observed for PRODAN in ether and ester lipids could be due to different dipolar relaxation of the immediate surroundings of the label, i.e., reorientation of lipid dipoles in the glycerol region and of water molecules residing therein.

Kinetics↗

Response of Bitot's spots in preschool children to vitamin A treatment.

In a double-masked, placebo-controlled, clinical trial in Indonesia, 88 preschool children between the ages of 36 and 72 months with Bitot's spots were randomly assigned to 200,000 IU of oral vitamin A or placebo and followed up for five weeks. Baseline and follow-up serum vitamin A levels were obtained. Of the 45 children receiving vitamin A, 33 (73.3%) showed complete cure and disappearance of Bitot's spots, six (13.3%) had disappearance of some but not all Bitot's spots, and six (13.3%) were unresponsive to treatment. The nonresponsive children were older, all male, and had higher initial mean serum vitamin A levels, 23.0 micrograms/dl, compared to 15.9 micrograms/dl in the cured group (P = .017). These data suggest that normal vitamin A status may be found in approximately 13% of children with Bitot's spots before vitamin A intervention and that one fourth of those who had Bitot's spots originally will not be cured of all Bitot's spots after intervention. These are important factors to consider when using Bitot's spots in prevalence surveys as a clinical sign of vitamin A deficiency.

Blindness↗

Isolation and characterization of ciliary neurotrophic factor from rabbit sciatic nerves.

Ciliary neurotrophic factor (CNTF) has been purified 35,000-fold to homogeneity from rabbit sciatic nerves using its ability to promote the survival of chick embryo ciliary ganglion neurons as the bioassay. The purification involved a combination of acid treatment, ammonium sulfate fractionation, hydrophobic interaction chromatography, chromatofocusing, preparative sodium dodecyl sulfate-polyacrylamide gel electrophoresis, and reversed-phase high performance liquid chromatography. Overlapping peptide sequences were obtained which accounted for 49% of the primary structure of the molecule. This information was used to prepare synthetic peptides in order to elicit antibodies. Purified CNTF exhibited two major and several minor bands between 24 and 22 kDa on silver-stained sodium dodecyl sulfate-polyacrylamide electrophoresis gels. All of the molecular forms were immunostained in Western blots by antiserum to synthetic peptides. The peptide sequences also provided a basis for cloning and expression of the rabbit CNTF gene (Lin, L-F. H., Mismer, D., Lile, J. D., Armes, L. G., Butler, E. T., III, Vannic, J. L., and Collins, F. (1989) Science 246, 1023-1025) confirming that the protein purified as reported here is CNTF.

Amino Acid Sequence↗

Interleukin-1 receptor antagonist activity of a human interleukin-1 inhibitor.

Three interleukin-1 inhibitors have been purified to homogeneity from medium conditioned by human monocytes. Partial sequence analysis and digestion with N-glycanase indicate that these are glycosylation forms of a single protein. The protein binds to the interleukin-1 receptor but has no interleukin-1-like activity, even at very high concentrations, and is therefore a pure receptor antagonist.

Amidohydrolases↗

Blindness and visual impairment in an American urban population. The Baltimore Eye Survey.

Data on the prevalence of blindness and visual impairment in multiracial urban populations of the United States are not readily available. The Baltimore Eye Survey was designed to address this lack of information and provide estimates of prevalence in age-race subgroups that had not been well studied in the past. A population-based sample of 5300 blacks and whites from east Baltimore, Md, received an ophthalmologic screening examination that included detailed visual acuity measurements. Blacks had, on average, a twofold excess prevalence of blindness and visual impairment than whites, irrespective of definition. Rates rose dramatically with age for all definitions of vision loss, but there was no difference in prevalence by sex. More than 50% of subjects improved their presenting vision after refractive correction, with 7.5% improving three or more lines. Rates in Baltimore are as high or higher than those reported from previous studies. National projections indicate that greater than 3 million persons are visually impaired, 890,000 of whom are bilaterally blind by US definitions.

Adult↗

Prevalence and significance of optic disc hemorrhage in a longitudinal study of glaucoma.

We determined the prevalence of hemorrhage within 1 disc diameter of the optic nerve head by masked examination of stereoscopic color and red-free fundus photographs in a multilayer study of 1123 patients. At the first (baseline) examination, disc hemorrhages were present in none of the normal subjects (0 of 661), 0.44% (6/1377) of "glaucoma suspect" subjects, and 2.44% (3/123) of glaucomatous eyes. Disc hemorrhage prevalence in glaucomatous eyes was significantly higher than in normal or glaucoma suspect eyes. Glaucoma suspect eyes with disc hemorrhage, compared with matched suspect eyes without disc hemorrhage, had a larger mean vertical cup-disc ratio, an increased rate of nerve fiber layer atrophy 1 year following disc hemorrhage, and a higher rate of conversion to initial visual field loss (numerically higher conversion though not statistically significant). While the number of eyes with disc hemorrhages in this study is small, in a patient with glaucoma or ocular hypertension, disc hemorrhage appears to be associated with a greater likelihood of ongoing damage. The low disc hemorrhage prevalence in an unselected population limits its usefulness as a screening tool for glaucoma.

Adult↗