Impact of clinical history on fracture detection with radiography

The effect of knowledge of localizing symptoms and signs in the detection of fractures was studied. Forty radiographs of the extremities were examined twice by seven radiologists; the sessions were separated by 4 months. In 26 cases, a subtle fracture was present; 14 cases were normal. In half of the cases at each session, the precise location of pain, tenderness, or swelling was provided. The observer was asked to determine if the case was normal or abnormal (provide the exact location of the fracture) and to indicate the degree of confidence in the diagnosis. Responses were converted to a numeric scale for analysis. Analysis of receiver operator characteristic parameters indicates that clues regarding location of trauma facilitate detection of fractures. The improvement is based largely on an increased true-positive rate without an increased false-positive rate, regardless of the decision criteria of the radiologist (overall willingness to "overread" or "underread"). This has direct clinical applicability and reinforces the plea of radiologists for precise clinical information.     

Lifelong food restriction prevents senile osteopenia and hyperparathyroidism in F344 rats

Studies were carried out on male F344 rats to examine the influence of aging and life-prolonging food restriction on bone and circulating parathyroid hormone levels. In ad libitum fed animals, the weight, density and calcium content of the femur increased with age and achieved their peak levels by 12 months of age. These levels remained stable until about 24 months and by 27 months of age the ad libitum fed animals had lost appreciable amounts of bone. The maturation of the femurs of the animals maintained on 60% of the ad libitum food intake was delayed and their bones were lighter, less dense and contained less calcium than bones from ad libitum fed rats of corresponding ages. But at 6, 12 and 24 months of age, the femur strength to body weight ratios were very highly significantly greater (P < 0.0001) for the restricted animals compared to the ad libitum fed controls. Circulating immunoreactive parathyroid hormone increased progressively with aging in the animals fed ad libitum and the animals that experienced bone loss at advanced age also had the highest level of the hormone. In contrast, in the food restricted animals aging was not associated with a marked increase in serum parathyroid hormone or with senile bone loss. The data are discussed in relation to the mechanism of the observed changes.     

Modulation of ion transport in cultured rabbit tracheal epithelium by lipoxygenase metabolites.

Lipoxygenase metabolites influence ion movement and fluid balance in the airways. We studied the effects of nordihydroguaiaretic acid (NDGA), a general inhibitor of the lipoxygenase pathway, on Na+ and Cl- secretion in cultured tracheal epithelial cells from adult rabbits through short-circuit current (Isc) and radioactive tracer flux experiments. NDGA inhibition of leukotriene release in freshly isolated rabbit tracheal epithelial cells was assayed by a 3H peptidyl-leukotriene radioimmunoassay. 3 microM NDGA resulted in a 91% reduction of leukotriene release. In unstimulated cultures, Cl- secretion (furosemide-inhibited fraction of Isc) was 11.1 +/- 2.8 muamp/cm2 (n = 10) and was unchanged in the presence of NDGA (n = 10). Epinephrine-stimulated Cl- secretion increased Isc by 12.2 +/- 2 muamp/cm2 (n = 10). This stimulation was unchanged by pretreatment with NDGA (n = 10), suggesting that inhibition of the lipoxygenase pathway did not affect Cl- secretion. In unstimulated cultures, Na+ absorption (amiloride-inhibited portion of Isc) was 10.7 +/- 3.3. muamp/cm2 (n = 10) and was reduced by 79% in the presence of NDGA (n = 10), suggesting that inhibition of the lipoxygenase pathway was associated with inhibition of Na+ absorption. Radioactive tracer flux experiments supported these findings. Exogenous LTD4 (n = 7) and LTC4 (n = 7) were added to cells pretreated with NDGA, and Na+ absorption was restored to 76% and 70% of control, respectively. In addition, LTD4 (n = 4) and LTC4 (n = 4) were added to cells without prior inhibition of the lipoxygenase pathway to NDGA and resulted in an increase in Cl- secretion.(ABSTRACT TRUNCATED AT 250 WORDS)     

Hydrolytic stability of pneumococcal group 6 (type 6A and 6B) capsular polysaccharides.

The hydrolyses of the immunologically cross-reactive and constitutionally isomeric group 6 pneumococcal polysaccharides, types 6A and 6B, were investigated by 31P nuclear magnetic resonance spectroscopy, gel filtration through Sepharose 4B, reducing-sugar analysis, and rocket immunoelectrophoresis. Phosphorus nuclear magnetic resonance spectroscopy showed that cleavage of the repeating-unit phosphodiester linkages at pH 10, 60 degrees C was considerably faster (greater than 10(3) ) for the type 6A than the type 6B polysaccharide. Under these reaction conditions, 31P nuclear magnetic resonance kinetic measurements showed that the Na+ form of the type 6A polysaccharide underwent phosphodiester-linkage hydrolysis two times slower than the corresponding Ca+2 form; a stoichiometrically excess amount of Ca+2 caused a 30-fold enhancement of the latter hydrolysis rate. The spectroscopic characterization of phosphorus-containing end groups resulting from hydrolysis of the type 6A polymer provided additional mechanistic information. Heating the type 6A and 6B polysaccharides at 56 degrees C for various times led to gel filtration coefficients of distribution (Kd values) which indicated that the type 6A material underwent size reductions considerably faster than did the type 6B antigen; these increased Kd values qualitatively correlated with the loss of immunochemical reactivity measured by rocket immunoelectrophoresis. The application of a statistical theory to the depolymerization of the type 6A and 6B polysaccharides was consistent with random bond cleavage, as evidenced by the calculated versus measured gel filtration patterns. Although the molecular changes causing the size reductions were not fully elaborated, it was established that the acetal linkages of the type 6A and 6B polysaccharides were comparatively resistant to hydrolysis and that depolymerization by hydrolysis of the phosphodiester linkage was a major factor only in the type 6A structure. It was concluded that the hydrolytic stability of the type 6B antigen would favor its use in the polyvalent pneumococcal vaccine rather than the cross-reactive, but comparatively unstable, type 6A polysaccharide, if all other factors are equal.     

Lung inflation and alveolar permeability to non-electrolytes in the adult sheep in vivo.

1. Experiments were performed on adult sheep to determine the effect of lung distension on the passive permeability of alveoli to water soluble non-electrolytes. With the animal breathing oxygen spontaneously, a segment of one lung was isolated by passing a balloon-tipped catheter through a tracheostomy into a distal bronchus. This isolated atelectatic segment was filled with an isosomotic saline solution containing radio-labelled solutes of known molecular size: [125I]albumin, [14C]inulin, [14C]-sucrose, [3H]mannitol, and [14C]urea. The segment was inflated with oxygen either to a preselected pressure, or to a predetermined fraction of its capacity. Inflation was then maintained for several 10-15 min periods between which the oxygen supply was disconnected and the saline sampled, allowing the tracer concentrations to be measured. 2. At low inflating pressures (20-32 cmH2O) and at low volumes (24-54% of capacity), alveolar permeability to water soluble solutes was slight and could be characterized in terms of a membrane penetrated by cylindrical water filled pores of 0-5-1-6 nm radius. In all experiments showing restricted diffusion, absorption of saline occurred. 3. There was a positive correlation between the degree of lung inflation and pore radius in both the pressure controlled and volume controlled experiments. At high inflating pressures and at inflation volumes which were close to the total capacity of the isolated segment, restriction of solute diffusion was lost; in five out of six such experiments there was a net movement of liquid into the alveoli. 4. These results can be explained by postulating that as the lung epithelium is progressively stretched there is an opening up of water filled channels between alveolar cells. At peak inflation, restriction of diffusion of water soluble solutes is lost, and the alveolar epithelium ceases to function as a barrier between the circulation and air spaces.     

A genetic linkage map for zebrafish: comparative analysis and localization of genes and expressed sequences

Genetic screens in zebrafish (Danio rerio) have isolated mutations in hundreds of genes with essential functions. To facilitate the identification of candidate genes for these mutations, we have genetically mapped 104 genes and expressed sequence tags by scoring single-strand conformational polymorphisms in a panel of haploid siblings. To integrate this map with existing genetic maps, we also scored 275 previously mapped genes, microsatellites, and sequence-tagged sites in the same haploid panel. Systematic phylogenetic analysis defined likely mammalian orthologs of mapped zebrafish genes, and comparison of map positions in zebrafish and mammals identified significant conservation of synteny. This comparative analysis also identified pairs of zebrafish genes that appear to be orthologous to single mammalian genes, suggesting that these genes arose in a genome duplication that occurred in the teleost lineage after the divergence of fish and mammal ancestors. This comparative map analysis will be useful in predicting the locations of zebrafish genes from mammalian gene maps and in understanding the evolution of the vertebrate genome.     

Changes in non-electrolyte permeability of alveoli and the absorption of lung liquid at the start of breathing in the lamb.

1. Experiments were done on mature foetal lambs, 135-145 days in gestation, exteriorized at Caesarean section, and on new-born lambs aged 12-60 hr. In the foetal lambs, test substances were added to lung liquid and then spontaneous ventilation was induced or the lungs were statically inflated with gas or saline. In the new-born lambs, the left lung was ventilated in order to maintain respiratory gas-exchange, while foetal lung liquid, taken from previous experiments and containing test substances, was introduced into the right lung, which was then inflated with gas and used for permeability measurements. In both foetuses and new-borns, the gas used was O2 or N2O and, at 20 min intervals, ventilation or static inflation was interrupted, the gas in the lungs absorbed into the circulation and the remaining liquid sampled through the trachea. The following test substances were used in various combinations: [14C]-erythritol, [3H]sucrose, [14C]inulin, [131I]albumin, and the polymer [131I]-PVP. The last of these was separated, after the experiments, by gel filtration with Sephadex G200 or G50, into fractions of defined molecular radius. [131I]albumin, or a large molecule fraction of [131I]PVP, was used as a volume marker. 2. Spontaneous ventilation was associated with the absorption of liquid and with an alteration in the foetal pattern of non-electrolyte permeability that could be characterized by postulating an opening up of water-filled cylindrical pores to 34-56 A in radium. In the new-born lambs, the results suggested pores 7-14 A in radius. 3. Static inflation of the foetal lungs with gas, to pressures of 25-35 cmH2O, gave permeabilities appropriate for pores 5-5-12 A in radius. Static inflation with gas, to pressures of 41-49 cmH2O, produced changes appropriate for much larger channels, more than 125 A in radius and possibly much larger. With one exception, expansion with saline produced changes similar to those obtained by gas inflation to 25-35 cmH20. 4. It was concluded that in the initial stages of pulmonary ventilation a change takes place in alveolar epithelial cells. The increase in size would be sufficient to allow for rapid liquid absorption, but is not so great as to permit significant penetration by plasma albumin. The results obtained in the lung of the new-born lamb statically inflated to 25-32 cmH2O suggest that, following the initial adaptation, alveolar permeability returns towards the foetal pattern, although the pores remain larger than in the foetus. The change in permeability pattern at birth appears to depend on the degree of lung expansion with gas.