Effects of Particle Abrasion Media and Pressure on Flexural Strength and Bond Strength of Zirconia.

OBJECTIVES: To compare the effects of particle abrasion medium and pressure on shear bond strength and biaxial flexural strength of three generations of zirconia (Lava Frame, Lava Plus, and Lava Esthetic) with the goal of optimizing the bond to zirconia. METHODS: 280 discs (14 mm diameter; 1 mm thickness) of each zirconia were milled and sintered. Specimens of each material were randomly distributed into 14 groups (n=20); half were tested for shear bond strength and half were tested for biaxial flexural strength. The specimens were particle abraded on one surface by 2 different media (50 µm alumina particles or 50 µm glass beads) for 10 seconds at three different pressures (15, 30, and 45 psi or 0.1, 0.2, 0.3 MPa). Untreated specimens served as positive control. A tube (1.50 mm diameter) filled with dual cured resin cement (Panavia SA) was placed onto the surface and light cured. Specimens were stored in water (37°C for 24 hours) and shear bond strength was measured in a universal testing machine (Instron). Biaxial flexural strength of each specimen was measured according to ISO 6872. Shear bond strength and biaxial flexural strength were compared individually with a 2-way analysis of variance (ANOVA) for factors surface treatment and zirconia composition. RESULTS: Significant differences were seen between surface treatments (p<0.01), zirconia composition (p<0.01) and their interaction (p<0.01) for both bond strength and flexural strength. With alumina particle abrasion, higher pressure produced higher bonds for Lava Frame and Lava Plus zirconia while the bond of Lava Esthetic declined with increased pressure. Higher pressure (>0.2 MPa or 30 psi) with alumina decreased biaxial flexural strength with Lava Esthetic zirconia. CONCLUSIONS: Particle abrasion with alumina produced a significantly better combination of bond strength while maintaining biaxial strength of three zirconia materials than particle abrasion with glass beads. The bond strength also depended upon the pressure of particle abrasion and the generation of zirconia used.

Demineralization Inhibition by Two Calcium-releasing Restorative Materials.

OBJECTIVE: To compare the ability of two calcium-releasing restorative materials to inhibit root dentin demineralization in an artificial caries model. METHODS AND MATERIALS: Preparations were made at the cementum-enamel junction of extracted human molars (40, n=10/material) and restored with two calcium-releasing materials (Experimental composite, Pulpdent Corporation and Cention N, Ivoclar Vivadent), a resin composite (Filtek Supreme Ultra, 3M Oral Care), and a resin-modified glass ionomer (RMGI) (Fuji II LC, GC). All materials (other than the RMGI) were used with an adhesive (Scotchbond Universal Adhesive, 3M Oral Care) in the self-etch mode, which was light cured for 10 seconds. All restorative materials were light cured in 2-mm increments for 20 seconds and then finished with a polishing disc. Teeth were incubated (37°C) for 24 hours in water. An acid-resistant varnish was painted onto the teeth around the restoration, leaving a 2-mm border of uncovered tooth. A demineralization solution composed of 0.1 M lactic acid, 3 mM Ca3(PO4)2, 0.1% thymol, and NaOH (to adjust pH=4.5), and a remineralization solution composed of 1.5 mM Ca, 0.9 mM P, and 20 mM Tris(hydroxymethyl)-aminomethane (pH=7.0) were prepared. Specimens were placed in the demineralization solution for 4 hours, followed by the remineralization solution for 20 hours and cycled daily for 30 days. The specimens were embedded, sectioned into 100-µm sections, and the interface between the restorative material and root dentin was viewed with polarized light microscopy. A line was drawn parallel with the zone of demineralization for each tooth. The area of "inhibition" (defined as the area external to the line) or "wall lesion" (defined as the area internal to the line) was measured with image evaluation software. Areas of inhibition were measured as positive values, and areas of wall lesions were measured as negative areas. RESULTS: A one-way analysis of variance (ANOVA) found significant differences between materials for "inhibition/wall lesion" areas in root dentin (p<0.001). Tukey post hoc analysis ranked materials (µm2, mean ±SD): Fuji II LC (5412±2754) > Cention N (2768±1576) and experimental composite (1484±1585) > Filtek Supreme Ultra (-1119±1029). CONCLUSION: The experimental composite and Cention N materials (used with an adhesive) showed net areas of inhibition greater than a reference resin composite, albeit at a lower level than a reference RMGI material (used with no adhesive).

Two-year Randomized, Controlled Clinical Trial of a Flowable and Conventional Composite in Class I Restorations.

OBJECTIVES: This study evaluated the two-year clinical performance and volumetric wear of a flowable resin composite compared to a conventional highly filled composite resin in Class I restorations. METHODS AND MATERIALS: In this single-center, single-blinded, comparator-controlled clinical study (Institutional Review Board approved), 120 carious teeth distributed in 60 patients were randomly assigned to four calibrated practitioners who placed occlusal restorations (n=60 flowable and n=60 conventional composite). Direct and indirect assessment at baseline, six months, one year, and two years occurred during which the modified Cvar and Ryge criteria were evaluated. Volumetric wear was determined by superimposition of profilometer scans of baseline and two-year casts. RESULTS: At two years, there was no significant difference in anatomic form (p=0.80), color match (p=0.08), marginal adaptation (p=0.89), marginal discoloration (p=0.79), surface integrity (p=0.18), secondary caries (p=0.66), cold sensitivity (p=0.522), occlusal sensitivity (p=0.818), or volumetric wear (p=0.661) between materials. Both materials showed a decrease in all criteria except secondary caries (p=0.95) over time. Two-year mean volumetric wear was 3.16 ± 2.38 mm(3) for the flowable composite and 3.43 ± 2.50 mm(3) for the conventional composite. CONCLUSIONS: The flowable and conventional composites used in this study have similar clinical efficacy after two years of service when placed as Class I occlusal restorations having isthmus widths less than one-half the intercuspal distance.

Lymphatic vessels arise from specialized angioblasts within a venous niche.

How cells acquire their fate is a fundamental question in developmental and regenerative biology. Multipotent progenitors undergo cell-fate restriction in response to cues from the microenvironment, the nature of which is poorly understood. In the case of the lymphatic system, venous cells from the cardinal vein are thought to generate lymphatic vessels through trans-differentiation. Here we show that in zebrafish, lymphatic progenitors arise from a previously uncharacterized niche of specialized angioblasts within the cardinal vein, which also generates arterial and venous fates. We further identify Wnt5b as a novel lymphatic inductive signal and show that it also promotes the 'angioblast-to-lymphatic' transition in human embryonic stem cells, suggesting that this process is evolutionarily conserved. Our results uncover a novel mechanism of lymphatic specification, and provide the first characterization of the lymphatic inductive niche. More broadly, our findings highlight the cardinal vein as a heterogeneous structure, analogous to the haematopoietic niche in the aortic floor.

Influence of Etching Protocol and Silane Treatment with a Universal Adhesive on Lithium Disilicate Bond Strength.

OBJECTIVES: To measure the effects of hydrofluoric acid (HF) etching and silane prior to the application of a universal adhesive on the bond strength between lithium disilicate and a resin. METHODS AND MATERIALS: Sixty blocks of lithium disilicate (e.max CAD, Ivoclar Vivadent) were sectioned into coupons and polished. Specimens were divided into six groups (n=10) based on surface pretreatments, as follows: 1) no treatment (control); 2) 5% HF etch for 20 seconds (5HF); 3) 9.5% HF etch for 60 seconds (9.5HF); 4) silane with no HF (S); 5) 5% HF for 20 seconds + silane (5HFS); and 6) 9.5% HF for 60 seconds + silane (9.5HFS). All etching was followed by rinsing, and all silane was applied in one coat for 20 seconds and then dried. The universal adhesive (Scotchbond Universal, 3M ESPE) was applied onto the pretreated ceramic surface, air thinned, and light cured for 10 seconds. A 1.5-mm-diameter plastic tube filled with Z100 composite (3M ESPE) was applied over the bonded ceramic surface and light cured for 20 seconds on all four sides. The specimens were thermocycled for 10,000 cycles (5°C-50°C/15 s dwell time). Specimens were loaded until failure using a universal testing machine at a crosshead speed of 1 mm/min. The peak failure load was used to calculate the shear bond strength. Scanning electron microscopy images were taken of representative e.max specimens from each group. RESULTS: A two-way analysis of variance (ANOVA) determined that there were significant differences between HF etching, silane treatment, and the interaction between HF and silane treatment (p<0.01). Silane treatment provided higher shear bond strength regardless of the use or concentration of the HF etchant. Individual one-way ANOVA and Tukey post hoc analyses were performed for each silane group. Shear bond strength values for each etch time were significantly different (p<0.01) and could be divided into significantly different groups based on silane treatment: no silane treatment: 0 HF < 5% HF < 9.5% HF; and RelyX silane treatment: 0 HF < 5% HF and 9.5% HF. CONCLUSIONS: Both HF and silane treatment significantly improved the bond strength between resin and lithium disilicate when used with a universal adhesive.

Reverse genetic screening reveals poor correlation between morpholino-induced and mutant phenotypes in zebrafish.

The widespread availability of programmable site-specific nucleases now enables targeted gene disruption in the zebrafish. In this study, we applied site-specific nucleases to generate zebrafish lines bearing individual mutations in more than 20 genes. We found that mutations in only a small proportion of genes caused defects in embryogenesis. Moreover, mutants for ten different genes failed to recapitulate published Morpholino-induced phenotypes (morphants). The absence of phenotypes in mutant embryos was not likely due to maternal effects or failure to eliminate gene function. Consistently, a comparison of published morphant defects with the Sanger Zebrafish Mutation Project revealed that approximately 80% of morphant phenotypes were not observed in mutant embryos, similar to our mutant collection. Based on these results, we suggest that mutant phenotypes become the standard metric to define gene function in zebrafish, after which Morpholinos that recapitulate respective phenotypes could be reliably applied for ancillary analyses.

Enamel wear opposing polished and aged zirconia.

Aging of dental zirconia roughens its surface through low temperature degradation. We hypothesized that age-related roughening of zirconia crowns may cause detrimental wear to the enamel of an opposing tooth. To test our hypothesis, we subjected artificially aged zirconia and reference specimens to simulated mastication in a wear device and measured the wear of an opposing enamel cusp. Additionally, the roughness of the pretest surfaces was measured. The zirconia specimens, artificially aged by autoclave, showed no significant increase in roughness compared to the nonaged specimens. Furthermore, no significant difference in material or opposing enamel wear between the aged and nonaged zirconia was seen. All zirconia specimens showed less material and opposing enamel wear than the enamel to enamel control or veneering porcelain specimens. Scanning electron micrographs showed relatively smooth surfaces of aged and nonaged zirconia following wear testing. The micrographs of the veneering ceramic showed sharp fractured edges and fragments of wear debris. Zirconia may be considered a wear-friendly material for restorations opposing enamel, even after simulated aging.

Evaluation of outgassing, tear strength, and detail reproduction in alginate substitute materials.

OBJECTIVE: To compare three alginate substitute materials to an alginate impression material for cast surface porosity (outgassing), tear strength, and detail reproduction. MATERIALS AND METHODS: Detail reproduction tests were performed following American National Standards Institute/American Dental Association (ANSI/ADA) Specification No. 19. To measure tear strength, 12 samples of each material were made using a split mold, placed in a water bath until testing, and loaded in tension until failure at a rate of 500 mm/min using a universal testing machine. For cast surface porosity testing, five impressions of a Teflon mold with each material were placed in a water bath (37.8°C) for the in-mouth setting time and poured with vacuum-mixed Silky Rock die stone at 5, 10, 30, and 60 minutes from the start of mixing. The gypsum samples were analyzed with a digital microscope for surface porosity indicative of hydrogen gas release by comparing the surface obtained at each interval with four casts representing no, little, some, and significant porosity. Data analysis was performed using parametric and Kruskal-Wallis analysis of variance (ANOVA), Tukey/Kramer post-hoc tests (α=0.05), and individual Mann-Whitney U tests (α=0.0167). RESULTS: All alginate substitute materials passed the detail reproduction test. Tear strength of the alginate substitute materials was significantly better than alginate and formed three statistically different groups: AlgiNot had the lowest tear strength, Algin-X Ultra had the highest tear strength, and Position Penta Quick had intermediate tear strength. Significant variation in outgassing existed between materials and pouring times (p<0.05). All alginate substitute materials exhibited the least outgassing and cast porosity 60 minutes after mixing. CONCLUSIONS: Detail reproduction and tear strength of alginate substitute materials were superior to traditional alginate. The outgassing effect was minimal for most materials tested. Alginate substitute materials are superior replacements for irreversible hydrocolloid.

Effect of light activation on resin-modified glass ionomer shear bond strength.

OBJECTIVE: Recent studies confirmed that resin-modified glass ionomers (RMGIs) set on the basis of two competing mechanisms, an acid-base reaction and a light-activated resin polymerization. This study evaluated the effect of the setting mechanism on bond strength by measuring the shear bond strength of three RMGIs to dentin with and without light activation. METHODS: Sixty human molars were ground to midcoronal dentin and randomly divided into six even groups: 1) Ketac Nano (KN), 2) KN without light cure (woLC), 3) Fuji Filling LC (FF), 4) FF woLC, 5) Fuji II LC (FII), and 6) FII woLC. The dentin surfaces of the specimens were conditioned/primed according to the manufacturers' instructions. A 1.54-mm diameter plastic tube was filled with RMGI material and affixed to the dentin surface. Groups 1, 3, and 5 were light cured for 20 seconds, and groups 2, 4, and 6 were immediately placed in a damp dark box with no light curing at 37°C for 24 hours. Shear bond strength testing was performed in an Instron device at 1 mm/min. Data were analyzed with a one-way analysis of variance (ANOVA) and Tukey/Kramer test (α=0.05). RESULTS: Mean ± standard deviation shear bond strength values (MPa) are: 7.1 ± 4.2 (KN), 11.7 ± 3.9 (FF), 10.2 ± 3.2 (FF woLC), 12.5 ± 5.1 (FII), and 0.3 ± 0.4 (FII woLC). Two KN, all KN woLC, and seven FII woLC specimens debonded before testing. Tukey/Kramer analysis revealed no significant differences in bond strength between the three light-cured RMGIs. KN and FII showed significantly lower bond strength without light cure, but no significant difference was observed between FF and FF woLC. CONCLUSIONS: The results of this study strongly suggest that light activation is necessary to obtain optimal bond strength between RMGI and dentin. FF may contain components that chemically activate resin polymerization. Clinically, KN and FII need to be light cured after placement of these RMGIs.

A genetic screen for vascular mutants in zebrafish reveals dynamic roles for Vegf/Plcg1 signaling during artery development.

In this work we describe a forward genetic approach to identify mutations that affect blood vessel development in the zebrafish. By applying a haploid screening strategy in a transgenic background that allows direct visualization of blood vessels, it was possible to identify several classes of mutant vascular phenotypes. Subsequent characterization of mutant lines revealed that defects in Vascular endothelial growth factor (Vegf) signaling specifically affected artery development. Comparison of phenotypes associated with different mutations within a functional zebrafish Vegf receptor-2 ortholog (referred to as kdr-like, kdrl) revealed surprisingly varied effects on vascular development. In parallel, we identified an allelic series of mutations in phospholipase c gamma 1 (plcg1). Together with in vivo structure-function analysis, our results suggest a requirement for Plcg1 catalytic activity downstream of receptor tyrosine kinases. We further find that embryos lacking both maternal and zygotic plcg1 display more severe defects in artery differentiation but are otherwise similar to zygotic mutants. Finally, we demonstrate through mosaic analysis that plcg1 functions autonomously in endothelial cells. Together our genetic analyses suggest that Vegf/Plcg1 signaling acts at multiple time points and in different signaling contexts to mediate distinct aspects of artery development.

Measurement of shock wave unsteadiness using a high-speed schlieren system and digital image processing.

A new method to measure shock wave unsteadiness is presented. Time-resolved visualizations of the flow field under investigation are obtained using a high-speed schlieren optical system and the motion of the shock wave is determined by means of digital image processing. Information on the shock's unsteadiness is subsequently derived with Fourier analysis. A sample study on shock unsteadiness in a shock-wave/turbulent boundary-layer interaction with separation is included. The method presented enables a measure of shock unsteadiness at locations in the imaged flow field not accessible by intrusive methods.

Preliminary work on the development of a novel detection method for osteoporosis.

Osteoporosis affects both the organic and mineral phases of bone resulting in a decrease in resistance to fracture. Dual x-ray absorptiometry (DEXA) scans are used for diagnosing osteoporosis, which is conventionally characterised by a decrease in mineral density. Unfortunately, some patients who suffer osteoporotic fractures have normal bone density, because both the organic and the mineral phase are affected. However, there are currently no methods of evaluating the health of the organic phase. Patients undergoing treatment for osteoporosis have reported hardening of their fingernails. As the properties of nail and bone may be linked in a comparable, measurable way, this work used both mechanical (nano-indentation) and chemical (Raman spectroscopy) methods to evaluate differences between fingernails sourced from osteoporotic and non-osteoporotic patients. The difference in mean modulus between the nails sourced from the groups was 1.1 GPa. The disulphide bond content of fingernail samples from each group was measured by Raman spectroscopy and disulphide bond content of fingernail was found to be significantly lower in the osteoporotic group. It can be concluded that a relationship between the mechanical and chemical properties of nail and bone may exist in a measurable way. This work has suggested that changes in the organic phase of bone are reflected in similar proteins, such as keratin, from which fingernails are composed. Collagen and keratin are two distinct structural proteins, but they share the need for protein sulphation and disulphide bond formation, via cysteine, for their structural integrity. A disorder of either process should lead to disordered collagen and keratin synthesis.

Distinct genetic interactions between multiple Vegf receptors are required for development of different blood vessel types in zebrafish.

Recent evidence indicates a specific role for vascular endothelial growth factor a (Vegfa) during artery development in both zebrafish and mouse embryos, whereas less is known about signals that govern vein formation. In zebrafish, loss of vegfa blocks segmental artery formation and reduces artery-specific gene expression, whereas veins are largely unaffected. Here, we describe a mutation in the zebrafish vegf receptor-2 homolog, kdra, which eliminates its kinase activity and leads to specific defects in artery development. We further find that Flt4, a receptor for Vegfc, cooperates with Kdr during artery morphogenesis, but not differentiation. We also identify an additional zebrafish vegfr-2 ortholog, referred to as kdrb, which can partially compensate for loss of kdra but is dispensable for vascular development in wild-type embryos. Interestingly, we find that these Vegf receptors are also required for formation of veins but in distinct genetic interactions that differ from those required for artery development. Taken together, our results indicate that formation of arteries and veins in the embryo is governed in part by different Vegf receptor combinations and suggest a genetic mechanism for generating blood vessel diversity during vertebrate development.

The use of fingernails as a means of assessing bone health: a pilot study.

BACKGROUND: Anecdotally, patients volunteer reports of increasing hardness of their fingernails within months of starting diverse treatments for osteoporosis. The properties of both nail and bone may be linked in a comparable, measurable way. METHODS: We examined the fingernails of two groups of patients, with (n = 9) and without (n = 13) osteoporosis at either the hip or lumbosacral spine. We performed nanoindentation to assess the degree of nail brittleness and Raman spectroscopy to assess the disulfide bond content of nail. RESULTS: The mean moduli of fingernails of patients with low bone mineral density (BMD) are lower than those of patients with normal BMD. The mean difference in mean modulus between the groups was found to be 0.996 (p = 0.15 between groups). The spectroscopy data also showed differences between the two sets of nails. The disulfide bond content of the nails sourced from osteoporotic patients was lower than that from healthy patients (p = 0.06 between groups). CONCLUSIONS: Bone collagen and nail keratin are two distinct structural proteins, and both require protein sulfation and disulfide bond formation, via cysteine, for structural integrity. A disorder of either process may lead to disordered collagen and keratin synthesis. This is reflected in the structural abnormalities seen in clinical syndromes in which there is either protein deficiency, disorders of sulfur metabolism, or cystathione beta-synthase deficiency. The relationship between nail and bone may exist in a measurable way. This pilot study should lead to further work to explore this relationship. Could nail prove to be a valuable adjunct to diagnosis or provide a means of more rapid follow-up after commencement of therapy?

A case-control study of dietary and erythrocyte membrane fatty acids in asthma.

BACKGROUND: Epidemiological evidence suggests that increased dietary omega-6 and reduced omega-3 fatty acid intake, may have contributed to the rising prevalence of asthma, but these hypotheses have not been tested in studies comparing both dietary intake and objective measures of polyunsaturated fatty acids. OBJECTIVE: To assess whether a higher intake of omega-6 or a lower intake of omega-3 fatty acids increases the risk of asthma, by measuring dietary fatty acid intake by a food frequency questionnaire (FFQ) and erythrocyte membrane fatty acids, as an objective biomarker of intake. METHODS: We have compared individual fatty acid intake estimated by FFQ and by mass spectrometry of fasting erythrocyte cell membranes in 89 cases of asthma and 89 community-matched controls. RESULTS: The odds of asthma were increased in relation to intake of the omega-3 fatty acids eicosapentaenoic acid (odds ratio (OR) for difference between the 25th and 75th centiles of intake= 1.89, 95% CI 1.15-3.11) and docosahexaenoic acid (OR = 2.11, 95% CI 1.19-3.74). There was no evidence of any difference in erythrocyte membrane levels of omega-3 fatty acids, while the odds of asthma were reduced in relation to linoleic acid (omega-6) membrane levels (OR = 0.45, 95% CI 0.21-0.95). CONCLUSION: These findings suggest that dietary omega-3 fatty acids do not play a major role in protecting against asthma, and that higher levels of erythrocyte membrane linoleic acid are associated with a lower risk of asthma.

The relationship between vitamin D and parathyroid hormone: calcium homeostasis, bone turnover, and bone mineral density in postmenopausal women with established osteoporosis.

It is evident from several studies that not all patients with hypovitaminosis D develop secondary hyperparathyroidism. What this means for bone biochemistry and bone mineral density (BMD) remains unclear. The aim of this study was to investigate the effects of hypovitaminosis D (defined as a 25OHD < or = 30 nmol/l) and patients with a blunted PTH response (defined arbitrarily as a PTH within the standard laboratory reference range in the presence of a 25OHD < or = 30 nmol/l) in comparison to patients with hypovitaminosis D and secondary hyperparathyroidism (defined arbitrarily as a PTH above the standard laboratory reference range in the presence of a 25OHD < or = 30 nmol/l) and vitamin D-replete subjects (25OHD > 30 nmol/l). Four hundred twenty-one postmenopausal women (mean age: 71.2 years) with established vertebral osteoporosis were evaluated by assessing mean serum calcium, 25OHD, 1,25(OH)2D, bone turnover markers, and BMD. The prevalence of hypovitaminosis D was 39%. Secondary hyperparathyroidism was found in only one-third of these patients who maintained calcium homeostasis at the expense of increased bone turnover relative to the vitamin D-replete subjects (bone ALP mean difference: 43.9 IU/l [95% CI: 24.8, 59.1], osteocalcin: 1.3 ng/ml [95% CI: 1.1, 2.5], free deoxypyridinoline mean difference: 2.6 nmol/nmol creatinine [95% CI: 2.5, 4.8]) and bone loss (total hip BMD mean difference: 0.11 g/cm2 [95% CI: 0.09, 0.12]). Patients with hypovitaminosis D and a blunted PTH response were characterized by a lower serum calcium (mean difference: 0.07 mmol/l [95% CI: 0.08, 0.2]), a reduction in bone turnover (bone ALP mean difference: 42.4 IU/l [95% CI: 27.8, 61.9], osteocalcin: 1.6 ng/ml [95% CI: 0.3, 3.1], free-deoxypyridinoline mean difference: 3.0 nmol/nmol creatinine [95% CI: 1.9, 5.9]), but protection in bone density (total hip BMD mean difference: 0.10 g/cm2, [95% CI: 0.08, 0.11]) as compared to those with hypovitaminosis D and secondary hyperparathyroidism. This study identifies a distinct group of patients with hypovitaminosis D and a blunted PTH response who show a disruption in calcium homeostasis but protected against PTH-mediated bone loss. This has clinical implications with respect to disease definition and may be important in deciding the optimal replacement therapy in patients with hypovitaminosis D but a blunted PTH response.

Amino acids and asthma: a case-control study.

Amino acids contribute to various anti-oxidant and immunological activities relevant to asthma pathogenesis, raising the possibility that differences in amino acids may be involved in asthma aetiology. The authors hypothesised that cystine reduces the risk of asthma via glutathione metabolism. Methionine, glutamine, glutamic acid and glycine may have potential protective effects, whilst arginine, phenylalanine and tryptophan may have adverse effects in asthma. Fasting plasma levels of amino acids were compared in a case-control study. A total of 89 adults, aged 18-65 yrs, with asthma controlled by inhaled corticosteroids, were recruited from a volunteer database and local primary care registers, and compared with 89 controls individually matched for age, sex and primary care centre. Contrary to the primary hypothesis, cases had higher fasting plasma cystine levels than controls, and there was no difference between cases and controls in any of the other amino acids tested, with the exception of plasma glycine, which was associated with a strongly reduced risk of asthma (odds ratio for the highest tertile compared to lowest 0.30 (95% confidence interval (0.11-0.82)). This study negates the hypothesis that higher fasting plasma cystine levels have a protective effect on the risk of asthma, although the inverse correlation with plasma glycine deserves further investigation.

Recovery of pregnancy mediated bone loss during lactation.

It is uncertain whether bone is routinely mobilised during pregnancy to provide calcium for the fetus and whether this is of a magnitude to cause osteoporosis. We have made sequential measurements of lumbar spine and hip bone mineral density (BMD) in 60 normal women before conception and then during the subsequent pregnancy out to one year after delivery. During pregnancy there was a significant fall in the BMD at the spine (1.53%), total hip (1.15%), and trochanter (3.90%) but not at the femoral neck. After delivery the women who breast-fed (n=34) showed a significant fall in BMD at all measurement sites (P<0.001) with the greatest change at the spine (4.7 +/- 3.1%) with 38% of women showing a change >5%. The women who bottle fed (n=10) increased or maintained BMD at all sites with the mixed feeders (n=16) showing an intermediate response. There was no consistent relationship between the change during pregnancy and lactation but 47% of the breast-feeders lost >5% at either the lumbar spine or trochanter. There was a good correlation between the change in BMD at these two sites (r=0.48, P<0.001). At 1 year after delivery all but 7 women had returned to within 5% of the preconceptual value at the spine and trochanter but the recovery at the total hip was less complete. Several women became transiently osteoporotic (T score below -2.5) at either spine or hip during reproduction of whom three started pregnancy with a normal BMD.

Longitudinal changes in bone mineral density during normal pregnancy.

Pregnancy is a common physiological event that could affect peak bone mass and the risk of developing osteoporosis later in life. There have been few longitudinal studies over a complete reproductive cycle of any size to show whether bone mineral density (BMD) changes. We have measured BMD by dual-energy X-ray absorptiometry in 46 normal women before conception and then again immediately after delivery and compared them with 30 control women who failed to conceive. Fifteen women were osteopenic in preconceptual BMD, but there was no difference between those who did or did not become pregnant. During pregnancy there was a small and statistically nonsignificant decline in BMD at all sites. The decrease at the trochanteric region was 4.2%, while losses at other sites were about 1%. The decline at the trochanter exceeded the least significant change between two measurements (5.04%) in 17 women (40.5%) with significant changes within individuals being much less common at the other measurement sites. The nonpregnant controls showed small increases in BMD of 0.3%-1.9% but no woman lost more than the least significant change. At the trochanter there was a significant difference (P = 0.013) between those who did and did not become pregnant. There was a good correlation between changes in BMD at all sites and no significant difference in the slope of these correlations between the pregnant and control groups. Correlations with lumbar spine were total hip, r = 0.46, P = 0.0001; femoral neck, r = 0.49, P = 0.0005; and trochanter, r = 0.66, P < 0.0001.

Effect of pregnancy and obstructive jaundice on inflammatory diseases: the work of P S Hench revisited.

Hench considered that cortisone improved inflammatory joint symptoms during pregnancy and obstructive jaundice. However, the improved symptoms are probably due to changes in the proportions of fatty acids in plasma and inflammatory cell phospholipids. These changes decrease the superoxide anions and eicosanoids produced and also reduce tumour necrosis factor alpha production.