Origin of Enriched Regulatory T Cells in Patients Receiving Combined Kidney-Bone Marrow Transplantation to Induce Transplantation Tolerance.

We examined tolerance mechanisms in patients receiving HLA-mismatched combined kidney-bone marrow transplantation (CKBMT) that led to transient chimerism under a previously published nonmyeloablative conditioning regimen (Immune Tolerance Network study 036). Polychromatic flow cytometry and high-throughput sequencing of T cell receptor-ß hypervariable regions of DNA from peripheral blood regulatory T cells (Tregs) and CD4 non-Tregs revealed marked early enrichment of Tregs (CD3+ CD4+ CD25high CD127low Foxp3+ ) in blood that resulted from peripheral proliferation (Ki67+ ), possibly new thymic emigration (CD31+ ), and, in one tolerant subject, conversion from non-Tregs. Among recovering conventional T cells, central memory CD4+ and CD8+ cells predominated. A large proportion of the T cell clones detected in posttransplantation biopsy specimens by T cell receptor sequencing were detected in the peripheral blood and were not donor-reactive. Our results suggest that enrichment of Tregs by new thymic emigration and lymphopenia-driven peripheral proliferation in the early posttransplantation period may contribute to tolerance after CKBMT. Further, most conventional T cell clones detected in immunologically quiescent posttransplantation biopsy specimens appear to be circulating cells in the microvasculature rather than infiltrating T cells.

Shorter mothers have shorter pregnancies.

We assessed whether maternal height was associated with gestational age in a cohort of 294 children born at term. Increasing maternal height was associated with longer pregnancy duration (p = 0.002). Stratified analyses showed that the main effect on pregnancy length appears to occur among shorter mothers (<165 cm tall), whose pregnancies were ∼0.6 and ∼0.7 weeks shorter than pregnancies of mothers 165-170 cm (p = 0.0009) and >170 cm (p = 0.0002) tall, respectively. Further, children of shorter mothers were more likely to be born early term than those of average height (p = 0.021) and taller (p = 0.0003) mothers. Maternal stature is likely to be a contributing factor influencing long-term outcomes in the offspring via its effect on pregnancy length.

Macrochimerism in Intestinal Transplantation: Association With Lower Rejection Rates and Multivisceral Transplants, Without GVHD.

Blood chimerism has been reported sporadically among visceral transplant recipients, mostly in association with graft-vs-host disease (GVHD). We hypothesized that a higher degree of mixed chimerism would be observed in multivisceral (MVTx) than in isolated intestinal (iITx) and isolated liver transplant (iLTx) recipients, regardless of GVHD. We performed a longitudinal prospective study investigating multilineage blood chimerism with flow cytometry in 5 iITx and 4 MVTx recipients up to one year posttransplant. Although only one iITx patient experienced GVHD, T cell mixed chimerism was detected in 8 out of 9 iITx/MVTx recipients. Chimerism was significantly lower in the four subjects who displayed early moderate to severe rejection. Pre-formed high-titer donor-specific antibodies, bound in vivo to the circulating donor cells, were associated with an accelerated decline in chimerism. Blood chimerism was also studied in 10 iLTx controls. Among nonsensitized patients, MVTx recipients exhibited greater T and B cell chimerism than either iITx or iLTx recipients. Myeloid lineage chimerism was present exclusively among iLTx and MVTx (6/13) recipients, suggesting that its presence required the hepatic allograft. Our study demonstrates, for the first time, frequent T cell chimerism without GVHD following visceral transplantation and a possible relationship with reduced rejection rate in MVTx recipients.

Deformational behaviour of knee cartilage and changes in serum cartilage oligomeric matrix protein (COMP) after running and drop landing.

OBJECTIVE: To investigate (1) the effect of running and drop landing interventions on knee cartilage deformation and serum cartilage oligomeric matrix protein (COMP) concentration and (2) if the changes in cartilage volume correlate with the changes in serum COMP level. METHODS: Knee joint cartilage volume and thickness were determined using magnetic resonance imaging (MRI) as well as COMP concentration from serum samples before and after in vivo loading of 14 healthy adults (seven male and seven female). Participants performed different loading interventions of 30 min duration on three different days: (1) 100 vertical drop landings from a 73 cm high platform, (2) running at a velocity of 2.2m/s (3.96 km), and (3) resting on a chair. Blood samples were taken immediately before, immediately after and 0.5h, 1h, 2h and 3h post intervention. Pre- and post-loading coronal and axial gradient echo MR images with fat suppression were used to determine the patellar, tibial and femoral cartilage deformation. RESULTS: Serum COMP levels increased immediately after the running (+30.7%, pre: 7.3U/l, 95% confidence interval (CI): 5.6, 8.9, post: 9.1U/l, 95% CI: 7.2, 11.0, P=0.001) and after drop landing intervention (+32.3%, pre: 6.8U/l, 95% CI: 5.3, 8.4; post: 8.9U/l, 95% CI: 6.8, 10.9, P=0.001). Cartilage deformation was more pronounced after running compared to drop landing intervention, with being significant (volume: P=0.002 and thickness: P=0.001) only in the lateral tibia. We found a significant correlation (r(2)=0.599, P=0.001) between changes in serum COMP (%) and in cartilage volume (%) after the drop landing intervention, but not after running. CONCLUSIONS: In vivo exercise interventions differentially regulate serum COMP concentrations and knee cartilage deformations. The relation between changes in COMP and in cartilage volume seems to depend on both mechanical and biochemical factors.

Elevated expression of adenosine A1 receptor in bronchial biopsy specimens from asthmatic subjects.

Asthmatics, unlike healthy subjects, experience bronchoconstriction in response to inhaled adenosine, and extracellular adenosine concentrations are elevated in the bronchoalveolar lavage fluid and exhaled breath condensate of asthmatic subjects. However, little is known about the location and expression of adenosine receptors in asthmatic airways. The aim of the present study was to investigate the distribution of adenosine A(1) receptors in bronchial biopsy specimens from mildly asthmatic steroid-naïve subjects and then compare the degree of expression with that of healthy subjects. Biopsy sections were immunostained using an adenosine A(1) receptor antibody, the selectivity of which was validated in specific experiments. Image analysis was then performed in order to determine differences in immunostaining intensity. Immunostaining of biopsy sections from the asthmatic subjects revealed strong expression of the A(1) receptor, located predominantly in the bronchial epithelium and bronchial smooth muscle. In comparison, very weak immunostaining was observed in biopsy specimens obtained from healthy subjects. Image analysis revealed that the intensity of positive staining of the asthmatic bronchial epithelium and smooth muscle regions was significantly greater than that observed for the healthy epithelium and smooth muscle. In conclusion, the sensitivity of asthmatics to inhaled adenosine coupled with increased adenosine A(1) receptor expression implies that these receptors play a role in the pathophysiology of this disease.

Services for children with diabetes.

This is the first assessment of the services available and care received by children and adolescents with Type 1 Diabetes in the Republic of Ireland. Questionnaires were mailed to 19 centres in 2006 identified as providing care for children and adolescents with Diabetes. Replies were received from all centres. 29 consultants provide care for a reported 2040 patients in the 19 centres. 16 (50%) paediatricians surveyed expressed a special interest in Diabetes while 27 (94%) see children in a designated Diabetes clinic. The average caseload per whole-time-equivalent (WTE) Diabetes Nurse Specialists (DNS) is 162 patients and 416 patients per WTE Dietician. 13 of the 19 centres (70%) have no access to Psychology services. This review of children's diabetes services highlights the current deficiencies, particularly in relation to support staff, with respect to international recommendations. Improvements in resources to reduce long-term complications needs urgent addressing at both local and national levels.

Mandibular phenotype of p20C/EBPbeta transgenic mice: Reduced alveolar bone mass and site-specific dentin dysplasia.

CCAAT enhancer binding proteins (C/EBP) comprise a family of basic-leucine zipper transcription factors that regulate cellular differentiation and function. To determine the role of C/EBP transcription factors in osteoblasts and odontoblasts, we generated a transgenic (TG) mouse model with Co1a1 (pOBCol3.6) promoter-targeted expression of a FLAG-tagged dominant negative C/EBP isoform, p20C/EBPbeta (previously LIP). Two of the four transgenic lines presented with abnormalities in the developing incisors, including breakage, overgrowth, and malocclusion. Histological examination revealed that the amount of alveolar bone was reduced in TG compared to wild-type (WT) mice. By microcomputed tomography (microCT), the bone volume fraction of the mandible was reduced at the level of the first and third molars, demonstrating a severe mandibular osteopenia. The lingual dentin morphology of TG incisors differed dramatically from WT. Labial dentin (enamel side) showed normal thickness and tubular dentin structure, whereas the lingual dentin was thinner (25-30% of WT at the alveolar crest) with an amorphous globular structure characteristic of dentin dysplasia. FLAG immunostaining was seen in both lingual and labial odontoblasts, indicating that the site-specific defect was not due to a lack of labial transgene expression. Northern blot analysis demonstrated reduced osteocalcin expression in TG mandibles, while bone sialoprotein was increased, consistent with prior results in calvariae and long bones. Dental sialophosphoprotein, a marker of the odontoblast lineage whose absence causes dentin dysplasia, was modestly reduced in TG mice by Northern blot and in situ hybridization analysis. By fluorescence microscopy, pOBCol2.3-GFP, a marker of the odontoblast lineage, was expressed in both labial and lingual odontoblasts, although GFP-marked lingual odontoblasts were more flattened than WT cells. Moreover, GFP-positive processes in the lingual dentin tubules were truncated and less organized than those in WT dentin. MicroCT analysis showed reduced tissue density in the lingual dentin. These data suggest that C/EBP transcription factors may be involved in the regulation of odontoblast polarization and dentin matrix production.

Mechanical characterization of porous nano-thin films by use of atomic force acoustic microscopy.

The indentation modulus of thin films of porous organosilicate glass with a nominal porosity content of 30% and thicknesses of 350nm, 200nm, and 46nm is determined with help of atomic force acoustic microscopy (AFAM). This scanning probe microscopy based technique provides the highest possible depth resolution. The values of the indentation modulus obtained for the 350nm and 200nm thin films were respectively 6.3GPa±0.2GPa and 7.2GPa±0.2GPa and free of the substrate influence. The sample with the thickness of 46nm was tested in four independent measurement sets. Cantilevers with two different tip radii of about 150nm and less than 50nm were applied in different force ranges to obtain a result for the indentation modulus that was free of the substrate influence. A detailed data analysis yielded value of 8.3GPa±0.4GPa for the thinnest film. The values of the indentation modulus obtained for the thin films of porous organosilicate glasses increased with the decreasing film thickness. The stiffening observed for the porous films could be explained by evolution of the pore topology as a function of the film thickness. To ensure that our results were free of the substrate influence, we analyzed the ratio of the sample deformation as well as the tip radius to the film thickness. The results obtained for the substrate parameter were compared for all the measurement series and showed, which ones could be declared as free of the substrate influence.

Biochemistry of Short-Chain Alkanes (Tissue-Specific Biosynthesis of n-Heptane in Pinus jeffreyi).

Short-chain (C7-C11) alkanes accumulate as the volatile component of oleoresin (pitch) in several pine species native to western North America. To establish the tissue most amenable for use in detailed studies of short-chain alkane biosynthesis, we examined the tissue specificity of alkane accumulation and biosynthesis in Pinus jeffreyi Grev. & Balf. Short-chain alkane accumulation was highly tissue specific in both 2-year-old saplings and mature trees; heart-wood xylem accumulated alkanes up to 7.1 mg g-1 dry weight, whereas needles and other young green tissue contained oleoresin with monoterpenoid, rather than paraffinic, volatiles. These tissue-specific differences in oleoresin composition appear to be a result of tissue-specific rates of alkane and monoterpene biosynthesis; incubation of xylem tissue with [14C]sucrose resulted in accumulation of radiolabel in alkanes but not monoterpenes, whereas incubation of foliar tissue with 14CO2 resulted in the accumulation of radiolabel in monoterpenes but not alkanes. Furthermore, incubation of xylem sections with [14C]acetate resulted in incorporation of radiolabel into alkanes at rates up to 1.7 nmol h-1 g-1 fresh weight, a rate that exceeds most biosynthetic rates reported with other plant systems for the incorporation of this basic precursor into natural products. This suggests that P. jeffreyi may provide a suitable model for elucidating the enzymology and molecular biology of short-chain alkane biosynthesis.

Evidence for an Elongation/Reduction/C1-Elimination Pathway in the Biosynthesis of n-Heptane in Xylem of Jeffrey Pine.

The biosynthetic pathway to n-heptane was investigated by examining the effect of the [beta]-keto acyl-acyl carrier protein synthase inhibitor (2R,3S)-2,3-epoxy-4-oxo-7E,10E-dodecadienamide (cerulenin), a thiol reagent ([beta]-mercaptoethanol), and an aldehydetrapping reagent (hydroxylamine) on the biosynthesis of n-[14C]heptane and putative intermediates in xylem sections of Jeffrey pine (Pinus jeffreyi Grev.& Balf.) incubated with [14C]acetate. Cerulenin inhibited C18 fatty acid biosynthesis but had relatively little effect on radiolabel incorporation into C8 fatty acyl groups and n-heptane. [beta]-Mercaptoethanol inhibited n-heptane biosynthesis, with a corresponding accumulation of radiolabel into both octanal and 1-octanol, whereas hydroxylamine inhibited both n-heptane and 1-octanol biosynthesis, with radiolabel accumulation in octyl oximes. [14C]Octanal was converted to both n-heptane and 1-octanol when incubated with xylem sections, whereas [14C]1-octanol was converted to octanal and n-heptane in a hydroxylamine-sensitive reaction. These results suggest a pathway for the biosynthesis of n-heptane whereby acetate is polymerized via a typical fatty acid synthase reaction sequence to yield a C8 thioester, which subsequently undergoes a two-electron reduction to generate a free thiol and octanal, the latter of which alternately undergoes an additional, reversible reduction to form 1-octanol or loss of C1 to generate n-heptane.

Rugby World Cup 2003 injury surveillance project.

OBJECTIVES: To study match injury patterns and incidence during the Rugby World Cup 2003 (RWC 2003); to compare these patterns and rates with comparative rugby injury data; and to assess differences between teams playing at different levels (eight finalists v 12 non-finalists). METHODS: Data were collected prospectively during the tournament. All injuries were recorded by the 20 participating team physicians. These were submitted to the tournament medical officer. An injury was defined as an event which forced a player either to leave the field or to miss a subsequent game or both. RESULTS: 189 injuries were recorded over 48 matches. This corresponds to 97.9 injuries per 1000 player-hours. Pool matches yielded a higher injury rate than non-pool matches. The 12 non-finalist teams sustained significantly higher injury rates than the eight finalist teams. The player positions open side flanker, inside centre, and number 8 were the most frequently injured positions. There was a low concussion rate, which may reflect under-reporting. The non-finalist teams had a higher rate of recurrent injury. CONCLUSIONS: The injury rate was higher than comparative data. Mismatches in the areas of skill, fitness, and the availability of resources for medical care of players may explain these differences.

Estrogenic and progestational activity of 7alpha-methyl-19-nortestosterone, a synthetic androgen.

Synthetic androgens exhibit estrogenic/antiestrogenic and progestational activities in addition to their androgenic effects. To investigate the pharmacological action of the synthetic androgen, 7alpha-methyl-19-nortestosterone (MENT), we examined its action in female rodents. The criteria employed for estrogenic/antiestrogenic effects were, uterine weight increase, vaginal cornification, induction of progesterone receptors (PR) synthesis and stimulation of peroxidase activity in the uteri of ovariectomized rats and mice. MENT increased uterine weight in a dose dependent manner, but did not cause vaginal cornification or stimulate PR synthesis in the uterus. The uterotropic activity of MENT was 200-fold lower than that of estradiol. Estrogen receptor (ER) bound [3H]-E2 was displaced by E2 and MENT with ED50 values of 70 pg and 250 ng, respectively, a 3,500 fold difference in their binding affinity. The low binding of MENT to ER, in contrast to its relatively high uterotropic action, suggested that receptors other than ER may be involved in its action on the uterus. The progestational activity of MENT in immature rabbits using the McPhail index assay was comparable to that of progesterone. Binding affinities of MENT and progesterone to PR were also comparable. However, the action of MENT on the uterus does not seem to be a progestational effect since mifepristone, an antiprogestin, had no effect on MENT-induced uterine growth. Specific androgen receptors (AR) in uterine cytosol were demonstrated. The involvement of AR in MENT action was confirmed by using an antiandrogen (flutamide) and an antiestrogen (ICI-182) in ovariectomized mice. Although MENT did not block the uterotropic effect of E2, it inhibited the E2-induced cornification of vaginal epithelium, induction of uterine PR synthesis and increase in uterine peroxidase activity in ovariectomized rats. The antiestrogenic effect of MENT was also blocked by flutamide. These results suggest that the uterotropic and antiestrogenic effects of androgens are mediated via AR. It is concluded that the increase in uterine weight caused by MENT is attributable to its anabolic effects.

Chronic toxicity and reversibility of antifertility effect of immunization against gonadotropin-releasing hormone in male rats and rabbits.

The chronic systemic toxicity of immunization with gonadotropin-releasing hormone, conjugated to tetanus toxoid (GnRH-TT), was investigated in male rats and rabbits in order to start Phase I clinical trials. Groups of rats and rabbits were immunized with GnRH-TT dissolved in aqueous adjuvant. The antigen was administered at weeks 0, 4, and 8, followed by boosters to maintain high antibody titers. At termination (8-9 months after first immunization), twenty rats and ten rabbits exhibiting the highest mean anti-GnRH titers and all the controls were selected for complete toxicological evaluation. In the rat study, a castrated control group was included for comparison with the immunized group. The hematological and serum chemistry parameters of immunized rats and rabbits were not affected in a significant manner. Most of the changes in serum chemistry of immunized rats were also found in castrated rats, indicating that the changes are most likely due to the withdrawal of androgenic support. The weights of the testes, epididymides, and sex accessory glands were lower in all immunized animals. There was significant atrophy of the germinal epithelium, which, however, sustained a population of Sertoli cells, spermatogonia, and pachytene spermatocytes. Other morphological changes in the prostate, seminal vesicles, pituitary, and mammary gland reflected the effect of androgen withdrawal. The decrease in the weight of liver, kidney, and heart seen in the immunized rats was also present in castrated rats and was not associated with any histopathological changes. The reversibility of immunization-induced infertility was investigated by mating the rats with normal females. Four months after the start of immunization, 9 out of 10 immunized rats were infertile whereas by nine months, all rats had regained fertility. Thus, it is concluded that immunization with GnRH-TT had no systemic toxicological effects in the adult male rats and rabbits for the period studied. The results also indicated that the GnRH-TT immunization had an antifertility effect in male rats. Fertility was restored following cessation of immunization and decline in anti-GnRH antibody titers.

Psychiatric diagnoses in children with alopecia areata.

OBJECTIVE: To identify psychiatric diagnoses in a sample of 12 children with alopecia areata (AA), to assess the possible relationship between life stressors and AA and to correlate any consistent physical findings to psychiatric data. METHOD: Twelve children with AA completed systematic psychiatric evaluations. The assessments included structured and semistructured interviews, rating scales, and parent checklists. Children had previously undergone immunological and endocrinological blood testing. RESULTS: Seven of the 12 subjects met criteria for anxiety disorders (including simple phobia) on structured interviews. An additional subject met criteria for dysthymia. Self-esteem measures indicated a high positive self-concept, and rating scales measuring anxiety and depression were within normal limits. No significant difference was found between mean number of positive or negative life events of children with AA compared with a normative sample. CONCLUSIONS: Although structured interviews revealed a higher than expected rate of anxiety or depressive disorders in this small clinical sample, self-report rating scales and semistructured interviews did not support the conclusion that significant psychopathology was present.

Automated sampling of in vitro dissolution medium: effect of sampling probes on dissolution rate of prednisone tablets.

The effect of sampling probe size and location on the in vitro dissolution rate of prednisone tablets was examined. Using USP XX Apparatus 2 with an automated sampling system, dissolution rates were determined using two types of large filter-tipped probes and a small capillary probe. Each probe was tested at three locations within the kettle. The large probes caused hydrodynamic changes which, when compared with results obtained through manual sampling, resulted in significant changes in dissolution rates at each location. These changes were less evident when the capillary probe was used, with an insignificant difference between results of automated and manual sampling when the capillary probe was placed midway between the paddle shaft and the kettle wall.

Systematic error associated with apparatus 2 of the USP dissolution test II: Effects of deviations in vessel curvature from that of a sphere.

Dissolution vessels made from glass or plastic are recognized by the USP as being suitable for dissolution testing. Glass vessels with a bottom inside curvature flatter than that of a sphere can cause a high bias in dissolution results; vessels with a steeper curvature can cause a low bias. The inside bottom curvature of plastic vessels adhered closely to the curvature of a sphere. The plastic vessels are preferable for use if the drug is not adsorbed and the vessel is not attacked by the dissolution medium. Bias in results between individual positions of a dissolution apparatus was traced to two shafts which were not vertical.

Gender differences in mediators of left ventricular hypertrophy in dialysis patients.

Left ventricular hypertrophy (LVH) is known to be a strong predictor of cardiovascular death in dialysis patients, but the mediators for its development remain to be clarified. In the non-renal population risk factors for LVH differ between the genders. We therefore studied 46 non-diabetic patients (26 male, 19 female) on maintenance hemodialysis (n = 25) or continuous ambulatory peritoneal dialysis (CAPD) (n = 20) all free from clinically evident cardiac disease, who underwent 48-hour ambulatory blood pressure (BP) monitoring, 2-D and M-mode echocardiography for left ventricular mass index (LVMI) and bloods for hemoglobin, parathyroid hormone (PTH), urea and electrolytes and liver function tests. Thirty-two out of 45 patients were taking antihypertensive drugs at the time of the study. The mean 48-hour BP was 135 +/- 19/83 +/- 13 mmHg and the mean LVMI was 144 +/- 50 g/m2. LVH (LVMI > 131 g/m2 men, > 100 g/m2 women) was present with equal frequency in both sexes: men 72% (18/25) and women 68% (13/19). Simple regression analysis showed that LVMI was correlated with 48-hour pulse pressure (r = 0.52, p < 0.00033), 48-hour systolic BP (r = 0.37, p < 0.05), PTH (r = 0.31, p < 0.04) and inversely with serum calcium (r = -0.29, p < 0.05) and hemoglobin (r = -0.33, p < 0.03). However, on multiple regression analysis pulse pressure (R2 = 28.7%), day systolic BP (R2 = 15.4%) and 48-hour systolic BP (R2 = 14.1%) were the only variables linked to LVMI. When the patients were split by gender, stepwise linear regression in the men showed a highly significant relationship between LVMI and pulse pressure (R2 = 37.1%) which was stronger at nighttime (R2 = 42.6%), but in females this was not apparent (R2 = 4.39%) and indeed no variable was linked to LVMI. Our study confirms that LVH is not only prevalent in dialysis patients but is present with equal frequency in both sexes. However the determinants of its development are different for each gender. In males pulse pressure, and therefore by implication vascular compliance, is important but in females, other unidentified factors predominate.

Synthesis and thermoelectric power of nitrogen-doped carbon nanotubes.

We have previously shown that high-purity multiwalled carbon nanotubes (pristine MWNTs) can be prepared from a mixture of xylene-ferrocene (99 at% C:1 at% Fe) inside a quartz tube reactor operating at approximately 700 degrees C. In a similar process, approximately 3 g of melamine (C3H6N6) was introduced during the growth of MWNTs to prepare nitrogen-doped nanotubes. The structural and electronic properties of nitrogen-doped MWNTs were determined by scanning electron microscopy, high-resolution transmission electron microscopy (HRTEM), electron energy loss spectroscopy (EELS), and thermopower measurements. The individual nitrogen-doped nanotube exhibits a bamboo-like structure and comprises 6-16 tube walls, as evidenced by HRTEM studies. The EELS measurements yielded an average nitrogen content of approximately 5 at% in the doped tubes. The thermoelectric power data of nitrogen-doped MWNTs remained negative even after exposure to oxygen for an extended period of time, suggesting that nitrogen doping of MWNTs renders them n-type, consistent with scanning tunneling spectroscopic studies on similar nanotubes.

Methods for measuring dermal penetration of pesticides.

The quantitation of percutaneous absorption of pesticides is required as part of the registration, re-registration or hazard assessment process. There is a paucity of regulatory guidelines in this area. This paper presents three protocols that can be used to quantitate percutaneous absorption, primarily as a result of continuous skin exposure over a period equivalent to a working day (8 hr). A rat in vivo protocol, an in vitro protocol and a human in vivo protocol are described. None of these protocols is considered to be ideal and/or to represent a preferred method. The final choice of protocol must take into account the toxicity and physicochemical properties of the test molecule as well as cost and resource/technical ability. Nevertheless, the protocols described allow percutaneous absorption to be quantitated, and it is believed that, if adopted, they will prove useful in the regulatory and research areas for the acquisition of data under standard defined conditions.

Toxicity of excess dicalcium phosphate in the diet of turkey poults.

High mortality in 1-week-old commercial turkey poults was attributed to the accidental substitution of dicalcium phosphate in the diet for corn. At necropsy of the affected birds, lesions were observed in the upper gastrointestinal tract, suggesting acute ingestion of a caustic substance. Mortality and gross and microscopic lesions were reproduced experimentally in turkey poults fed diets similar to the diet fed in the field case. The cause of these lesions was attributed to increased pH due to the phosphoric acid content of the diet.