Screening of neonatal instability and of developmental dislocation of the hip. A survey of 132,601 living newborn infants between 1956 and 1999.

Between 1956 and 1999, 132,601 living children were born in Malmö, and screened for neonatal instability of the hip. All late diagnosed patients have been followed and re-examined clinically and radiologically. During the first years of screening, less than five per 1,000 living newborn infants were treated. This figure increased to 35 per 1000 in 1980, but later diminished again to about six per 1,000 annually after 1990. The number of referred cases decreased from 45 per 1,000 in 1980 to between 10 to 15 per 1,000 from 1990. During the period of high rates of referral and treatment a larger number of paediatricians were involved in the screening procedure than during the periods with low rates of ferral and treatment. Altogether 21 patients (0.16 per 1,000) with developmental dislocation of the hip were diagnosed late, after one week. At follow-up, 18 were free from symptoms and 15 considered to be diologically normal.

The influence of complexing agents on the solubility and absorption of aluminium in rats exposed to aluminium in water.

The influence of citrate (0-31 mM), fluoride (0 or 2.6 mM) and silicate (0 or 2.6 mM) on the absorption of Al (0-18 mM) was studied in rats. We tested the hypothesis that the solubility and absorption of Al increases in the gastrointestinal (GI) tract in the presence of the complexing agents. Male rats were exposed for 6 or 7 weeks to soluble Al in acidic drinking water (pH 2.5-3.0) with or without the complexing agents. At the end of exposure Al was fractionated in the stomach content, in order to study if the solubility of Al was changed after ingestion. Al absorption was estimated by Al analysis of the right femur bone. Speciation calculations indicated that citrate and fluoride caused formation of soluble Al-citrate (97%) and -fluoride (> 60%) complexes in the water. Silicate did not affect the theoretical speciation. In all cases, a large fraction of soluble Al became insoluble in the stomach after ingestion. The concentration of soluble Al increased only in the presence of citrate or a mixture of fluoride and silicate, but citrate was the only complexing agent that influenced the absorption of Al in the rat. This indicates that the form of Al may be changed in the GI tract when soluble drinking-water Al is ingested, and that the solubility of Al in drinking water and GI tract may not be good predictors of the bioavailability of Al even when chelating agents are present.

Instability of the hip in neonates. An ethnic and geographical study in 24,101 newborn infants in Malmö.

In a prospective study conducted between 1990 and 1997, 24 101 newborn infants were examined for neonatal instability of the hip and classified by the ethnic origin of their parents. In 63% their mother and father were of Swedish extraction and in 24% they were born in a foreign country. Those of foreign extraction were split into ethnic and geographical subgroups. Although the incidence of treated (dislocatable-unstable) hips was greater in Swedes (7.6/thousand), than in other geographical groups (5.8/thousand) it was not significantly different (p = 0.065). A total of 12.7/thousand were referred from the neonatal ward to the orthopaedic clinic with suspected dislocatable or unstable hips; 6.8/thousand were treated (5.4/thousand dislocatable, 1.4/thousand unstable), but 5.9/thousand were not treated since their ultrasound examination was normal. Two hips were diagnosed late and one case of mild avascular necrosis was found. Examination by dynamic ultrasound decreased the number of treated cases by 5.9/thousand but was not an absolute guarantee of diagnosis.

Does aluminium stimulate the immune system in male rats after oral exposure?

The influence of oral aluminium exposure on the immune system was studied in rats. Male rats were exposed to soluble and labile Al in acidic drinking water (0-500 mg Al/l) for 7-9 weeks. The concentration of Al in femur bone was higher in rats exposed to 50 and 500 mg Al/l (mean concentration 277 and 599 ng Al/g) than in control rats (150 ng Al/g). The Al concentration in blood plasma could only be quantified in the 500 mg/l group (mean 2.7 ng/ml), whereas the concentrations in the control and 50 mg/l groups were low (< 2 ng Al/ml). Exposure of 4-13-weeks-old rats to the highest Al concentration caused an increased number of splenocytes, whereas exposure of 9-16-weeks-old rats to 500 mg Al/l caused an increased number of thymocytes. Moreover, the proliferative response of splenocytes to the mitogen Con A (2 micrograms/ml) was increased by exposure of the 9-16-weeks-old rats to 500 mg Al/l as compared with the controls. The results indicate that oral Al exposure caused a slight stimulation of some immune functions in the rat at Al plasma concentrations normally found in the human population (< 10 ng Al/ml).

Concentration-dependent absorption of aluminum in rats exposed to labile aluminum in drinking water.

The hypothesis was tested that the absorption of labile Al in rats will increase when the Al-binding capacity of food components in the stomach is saturated. Male rats were exposed to 0, 10, 50, or 500 mg labile Al/L in acidic drinking water (pH 3) for 9 wk. The results show that labile Al in drinking water is complexed by feed constituents in the stomach of the rat in vivo, thus causing a nondetectable absorption of Al at 10 mg Al/L. An increased absorption of Al at 50 and 500 mg Al/L was associated with a saturation of the Al-binding capacity of feed components in the lumen of the stomach, causing the appearance of labile Al. Thus, the presence of labile Al in drinking water does not necessarily result in a high Al absorption when the water is ingested, since the bioavailability of labile Al is dependent both on the amount and composition of Al-binding components present in the gastrointestinal tract at the time of ingestion of the water. It is thus not possible to predict the body burden of Al in humans just by measuring the Al concentrations in drinking water. Even a further refining of the exposure measurement to include speciation of Al in the water may not markedly improve the prediction of the Al body burden. Future epidemiological studies must therefore be based on actual measurements of Al concentration in tissues or fluids from the study subjects.

Effective Sample Size in Diffuse Reflectance Near-IR Spectrometry.

Two independent methods for determination of the effectively sampled mass per unit area are presented and compared. The first method combines directional-hemispherical transmittance and reflectance measurements. A three-flux approximation of the equation of radiative transfer is used, to separately determine the specific absorption and scattering coefficients of the powder material, which subsequently are used to determine the effective sample size. The second method uses a number of diffuse reflectance measurements on layers of controlled powder thickness in an empirical approach. The two methods are shown to agree well and thus confirm each other. From the determination of the effective sample size at each measured wavelength in the visible-NIR region for two different model powder materials, large differences was found, both between the two analyzed powders and between different wavelengths. As an example, the effective sample size ranges between 15 and 70 mg/cm(2) for microcrystalline cellulose and between 70 and 300 mg/cm(2) for film-coated pellets. However, the contribution to the spectral information obtained from a certain layer decreases rapidly with increasing distance from the powder surface. With both methods, the extent of contribution from various depths of a powder sample to the visible-NIR diffuse reflection signal is characterized. This information is valuable for validation of analytical applications of diffuse reflectance visible-NIR spectrometry.

Evaluation techniques for two-way data from in situ fourier transform mid-infrared reaction monitoring in aqueous solution.

A model chemical reaction was monitored with in situ Fourier transform mid-infrared spectroscopy using an attenuated total reflectance probe. The evaluation of the IR spectra is complicated by the fact that the reaction runs in nonisothermal aqueous solution with large variations in pH. Despite this, it was possible to extract large amounts of useful information on the reaction after suitable pretreatment of the spectra. Alternating least-squares (ALS) multivariate curve resolution is shown to be a useful technique for obtaining pure component spectra and concentrations if suitable spectral regions are analyzed. Rank mapping methods are used as the basis for this sectioning into smaller regions. Techniques for finding and analyzing selective spectral regions are also shown to be applicable to this type of data. Partial least-squares (PLS) regression models based on spectral data were used to verify the results where possible. The correlation between the concentrations predicted from PLS and ALS is excellent.

Bioavailability of labile aluminium in acidic drinking water: a study in the rat.

The bioavailability of labile Al (Allab; Al3+, and monomeric hydroxo and sulfato complexes) in drinking water was studied in the rat. The hypothesis was that Allab in drinking water is more available for absorption in the gastro-intestinal tract than Al complexed in the rat feed. Male Sprague-Dawley rats were exposed to 4 mg Al/litre in acidic drinking water (pH 4-5) and 5 mg Al/kg in the feed for 10 wk. The Al intake of these rats was about twice that in a control group of rats that received Al only in the feed. Both a theoretical speciation calculation and a speciation analysis of the water in a flow injection system showed that more than 98% of the Al in the water was present as Allab. However, intake of this water did not result in increased levels of Al in the bone, liver or brain tissue of the rats. Al speciation in a simulated rat stomach indicated that Allab in drinking water is rapidly complexed by feed constituents as the water enters the acidic milieu of the stomach, resulting in a very low concentration of Allab. The concentration of dissolved Al was also low in comparison to the added amount of labile Al. The possibility of complex formation between Allab and feed components in the gastro-intestinal tract should be taken into account in further studies of the bioavailability of drinking water Al in experimental animals and in humans.

Aluminium fractionation in a simulated rat stomach: an in vitro study.

This study is part of a project dealing with the absorption of aluminium in rats from acidified drinking water. The hypothesis of the project was that 'labile' forms of aluminium in water might be more available for absorption than aluminium in food. To investigate this hypothesis, the distribution of species of the metal within the rat stomach must be considered. So far, few attempts in this direction have been made. The distribution of aluminium forms in vitro was studied, simulating the conditions present in a rat stomach. The in vitro set-up is based on methods used for drug release studies. The results show that only part of the aluminium (29-54%) added in 'labile' forms at a concentration of 4.0 mg l-1 Al was detected as total dissolved aluminium (Altot) after incubation in a simulated rat stomach. The levels of 'quickly reacting aluminium' (Alqr) (approximately the sum of Al and its monomeric hydroxo and sulfato complexes) were very low (< 0.2 mg l-1), but difficult to quantify precisely in this matrix. The pattern of the in vitro results was confirmed by measurements in pooled rat stomachs from in vivo experiments. There are obviously considerable amounts of ligands present in rat feed that bind strongly to aluminium and thereby affect the distribution of metal species inside the rat stomach. It is believed that phosphoserine, present in the protein casein, is an important ligand for aluminium complexation in this case. The results show that studies of Al absorption should be accompanied by fractionation measurements within simulated or real gastric systems.

Mechanized determination of n-octanol/water partition constants using liquid-liquid segmented flow extraction.

A simple and rapid method for the determination of partition constants in the n-octanol/water system is presented. The substance under study is dissolved in n-octanol or water, and injected into a stream of the corresponding phase. Liquid-liquid segmented flow is utilized for equilibration of the two phases and after equilibration a fraction of the aqueous phase is separated with the aid of a hydrophilic membrane. The amount of substance in the aqueous phase is measured spectrophotometrically. The measurements are repeated at a small number of different phase flow ratios and the results obtained are plotted against these ratios. From slope and intercept for the regression line through these points the conditional partition constant, D', can be calculated. A simplified procedure using only two measurements, one of which is obtained with the flow rate of organic phase set to 0, can also be used. Partition constants in the range 0.48 < D < 873 (-0.32 < log D < 2.94) have been determined using this system. The precision, measured as relative standard deviation (RSD) is below 15%, corresponding to a standard deviation of +/- 0.1 log unit or less over the range of measurement. Measured values correspond to literature values within 0.07 log units. The time needed for a determination is about 15 min per substance, in many cases even shorter and the sample consumption is, in most cases, less than 1 mg.

Evaluation of partition measurements in liquid-liquid segmented flow.

The different configurations possible for an FIA extraction system for partition measurements have been tested and the corresponding evaluation formulae based on determinations at different phase flow ratios, verified. Increased flexibility results from the possibility of using samples dissolved in either aqueous or organic phase. Choosing the best configuration in every case makes it possible to extend the range of measurable conditional partition constants without excessive losses in precision.

Incidence and prognosis of coxarthrosis. 1964.

To define radiographic criteria, the radiographs of all patients diagnosed with coxarthrosis during the year 1951 were reviewed. Structural or joint space changes, evident radiographically in one of every seven cases in 1951, persisted at the time of the review in 1962. In the remaining cases, the diagnosis had been based upon the presence of osteophytic changes alone. Only one of 86 such cases reviewed in 1962 had structural or joint space changes. Osteophytes had no clinical significance and did not progress to coxarthrosis. Osteophytes appear to be a part of normal age changes. The radiographic diagnosis of coxarthrosis must be based on the demonstration of structural or joint changes. The natural history of coxarthrosis was studied by observing the course of the disease over a ten-year period in all patients (168) with primary and secondary disease diagnosed during the five-year period, 1950-1954. About one in nine cases in this series was classified as secondary, and the sexes were equally well represented. The occurrence of bilateral disease in one third of the patients strongly suggested that primary coxarthrosis is a disease sui generis. Four out of ten patients died within ten years of diagnosis of the disease.

Incidence of congenital clubfoot in Sweden. 128 cases in 138,000 infants 1946-1990 in Malmö.

The incidence of congenital clubfoot, neurological disorders excluded, was studied over a period of 45 years (1946-1990). The number of children, born alive with clubfoot, and detailed census data for the period were available. Altogether 137,614 living infants were born and of these 128 had congenital clubfoot. 56 (44 percent) were bilateral and 101 (79 percent) were boys. The overall incidence was 0.93 per thousand children. The annual incidence rose during the 45-year-period. This was, however, fully explained by the higher incidence among children of non-Nordic extraction.

Rapid determination of conditional partition constants in an FIA system.

This paper presents a simple and rapid method for the screening of substances for their conditional partition constants in the chloroform-water system. Samples are injected in either aqueous or organic solution into the corresponding phase. After equilibration in segmented flow the amount of sample remaining is measured photometrically. Performing the measurements at a series of phase volume ratios enables calculation of conditional partition constants knowing neither the amount injected nor the absorptivity of the substance under study. The time needed for a determination is about 15 min per substance, in many cases even shorter and the sample consumption is, in most cases, less than 1 mg. These characteristics make the method suitable for screening purposes. A series of compounds has been examined with this method, and acceptable results for the conditional partition constants were obtained in the range 0.2 less than D' less than 100 (-0.7 less than log D' less than 2.0).

Application of a multichannel dropping dispenser in segmented continuous flow analysis.

A simple dual channel dropping dispenser has been used for the simultaneous introduction of aqueous solutions of sample and reagent directly into a continuous flow of an organic solvent. Each aqueous segment forms an enclosed reaction system, completely surrounded by a film of the organic phase, which prevents any carry over between segments. An analytical signal is measured directly on the moving segments of precisely defined volumes of the homogenized reaction mixture. The applicability of this "microbatch" technique for the determination of light-absorbing species, for sample dilution and one-standard calibration, and for providing acid-base titrations on a microlitre scale is demonstrated with simple examples.

Juxtacellular histamine concentration governs histamine release from rat peritoneal mast cells.

Isolated rat peritoneal mast cells release histamine when superfused with isoosmotic salt or sucrose solutions. The release was ascribed by us to an intracellular ion exchange between potassium and histamine at granule sites, resulting from a flux of cytoplasmic potassium across the granules secondary to the disturbance of the 'state of equilibrium' at the cell surface caused by the superfusion (Uvnäs et al. 1989). In the present article is shown that the histamine releasing effect is counteracted by the addition of histamine to the superfusion fluid. The inhibition is concentration-dependent and accompanied by concomitant changes in the potassium efflux. A 50% inhibition of the histamine release requires an external histamine concentration of 40 microM and extrapolation of the equilibrium curve hints at a total inhibition at concentrations around 170 microM. The observations are taken to indicate that reduction of the juxtacellular histamine concentration caused by the superfusion disturbs the histamine equilibrium at the mast cell surface resulting in the activation of the histamine secretory mechanism. In other words, the secretory activity of the mast cell is checked by the juxtacellular concentration of histamine. When the juxtacellular histamine is removed e.g. on isolation procedures, other experimental situations such as superfusion, or by consumption in vivo the mast cell delivers histamine to restore the juxtacellular equilibrium.

Staple fixation of osteotomy for cubitus varus. A simple technique used in 11 children.

Eleven children with a persistent varus deformity of 15 degrees or more were operated on with a supracondylar lateral closing-wedge osteotomy. The osteotomy was stabilized with a staple after predrilling for the legs of the staple. No displacement occurred in the osteotomy. The results were excellent in all the cases.

Comparison of segmentors for liquid-liquid extraction flow-injection analysis.

The segmentation of two immiscible solvents in a continuous liquid-liquid extraction flow system has been studied with a computer-controlled photometric detection system (resolution time approximately 3 msec). The T-shaped segmentors tested were made of fluoroplastic, glass (A4-T fitting) and a modified glass (A8-T fitting). The modified A8-T fitting gave the most repeatable segmentation (rsd approximately 2%).