Effect of disodium fumarate on microbial abundance, ruminal fermentation and methane emission in goats under different forage: concentrate ratios.

This study investigated the effects of disodium fumarate (DF) on methane emission, ruminal fermentation and microbial abundance in goats under different forage (F) : concentrate (C) ratios and fed according to maintenance requirements. Four ruminally fistulated, castrated male goats were used in a 4 × 4 Latin square design with a 2 × 2 factorial arrangement of treatments and the main factors being the F : C ratios (41 : 59 or 58 : 42) and DF supplementation (0 or 10 g/day). DF reduced methane production (P < 0.05) on average by 11.9%, irrespective of the F : C ratio. The concentrations of total volatile fatty acids, acetate and propionate were greater in the rumen of goats supplemented with DF (P < 0.05), whereas the abundance of methanogens was lower (P < 0.05). In high-forage diets, the abundance of Selenomonas ruminantium, a fumarate-reducing bacterium, was greater in the rumen of goats supplemented with DF. The abundance of fungi, protozoa, Ruminococus flavefaciens and Fibrobacter succinogenes were not affected by the addition of DF. Variable F : C ratios affected the abundance of methanogens, fungi and R. flavefaciens (P < 0.05), but did not affect methane emission. The result implied that DF had a beneficial effect on the in vivo rumen fermentation of the goats fed diets with different F : C ratios and that this effect were not a direct action on anaerobic fungi, protozoa and fibrolytic bacteria, the generally recognized fiber-degrading and hydrogen-producing microorganisms, but due to the stimulation of fumarate-reducing bacteria and the depression of methanogens.

Preclinical evaluation of dual PI3K-mTOR inhibitors and histone deacetylase inhibitors in head and neck squamous cell carcinoma.

BACKGROUND: We examine the potential value of a series of clinically relevant PI3K-mTOR inhibitors alone, or in combination with histone deacetylase inhibitors, in a model of head and neck squamous cell carcinoma (HNSCC). METHODS: Head and neck squamous cell carcinoma cell lines, human keratinocyte and HNSCC xenograft models were treated with histone deacetylase inhibitors (HDACIs) and new generation PI3K and dual PI3K-mTOR inhibitors either alone or in combination. Cell and tumour tissue viability and proliferation were then determined in vitro and in vivo. RESULTS: Phosphatidylinositol-3-phosphate kinase, AKT and dual PI3K-mTOR inhibitors caused marked in vitro enhancement of cytotoxicity induced by HDACIs in HNSCC cancer cells. This effect correlates with AKT inhibition and is attenuated by expression of constitutively active AKT. Histone deacetylase inhibitor and phosphatidylinositol-3-phosphate kinase inhibitors (PI3KIs) inhibited tumour growth in xenograft models of HNSCC. Importantly, we observed intratumoural HDAC inhibition and PI3K inhibition as assessed by histone H3 acetylation status and phospho-AKT staining, respectively. However, we saw no evidence of improved efficacy with an HDACI/PI3KI combination. INTERPRETATION: That PI3K and dual PI3K-mTOR inhibitors possess antitumour effect against HNSCC in vivo.

[The efficacy of parenteral nutrition with different energy for systemic inflammatory response syndrome (SIRS) in the aged].

To evaluate the efficacy and safety of parenteral nutrition (PN) with lower or higher energy for treating systemic inflammatory response syndrome (SIRS) in the aged, thirty old SIRS critically ill patients were involved in a randomized control clinical trial. Fifteen cases were treated by PN with lower energy (105 KJ.kg-1.d-1), and another fifteen cases with higher energy (146 KJ.kg-1.d-1) for 6 days. The data about metabolisms of protein, glucose and fat, blood gas analysis, acute physiology and chronic health evaluation (APACHE II) were analysed. The results showed that: 1. The effects of 105 KJ.kg-1.d-1 PN in increasing organism protein and maintaining nitrogen balance were the same as those of 146 KJ.kg-1.d-1 PN. 2. The levels of fast blood sugar and triglyceride maintained unchanged in 105 KJ.kg-1.d-1 PN group, while they increased significantly in 146 KJ.kg-1.d-1 PN group(P < 0.05). 3. PaO2 was raised greatly in 105 KJ.kg-1.d-1 PN group, while not in 146 KJ.kg-1.d-1 PN group. 4. 105 KJ.kg-1.d-1 PN and 146 KJ.kg-1.d-1 PN decreased APACHE II(P < 0.05), but the efficiency of 105 KJ.kg-1.d-1 PN was better than that of 146 KJ.kg-1.d-1 PN (P < 0.05). We conclude that PN with 105 KJ.kg-1.d-1 energy intake is more effective and safer for treating SIRS than that with 146 KJ.kg-1.d-1 in the aged.

The veterans healthcare system: preparing for the twenty-first century.

Since its establishment in 1946, the veterans healthcare system has greatly expanded in both size and responsibility. It is now the largest integrated healthcare system in the United States, the nation's largest provider of graduate medical and other health professionals training, and one of the largest research enterprises in America. It is also the nation's largest provider of services to homeless persons, an essential provider in the public healthcare safety net, and an increasingly important element in the federal response to disasters and national emergencies. Patterned after what was considered the best in American healthcare, for most of the past 50 years the Department of Veterans Affairs (VA) healthcare has focused primarily on acute inpatient care, high technology, and medical specialization. Now, in response to societal and industrywide forces, the Veterans Health Administration (VHA) is reengineering the veterans healthcare system, changing the operational and management structure from individual hospitals to 22 integrated service networks and transitioning the system to one that is grounded in ambulatory and primary care. This article briefly describes the history and functions of the veterans healthcare system, its service population, and key aspects of its restructuring.

Lipid abnormalities in Turner syndrome.

Turner syndrome is associated with insulin resistance, increased incidence of type II diabetes, and hypertension, all of which are cardiovascular risk factors. The purpose of this study was to evaluate the lipid profile of girls with untreated Turner syndrome, (aged 5 to 14 years; 68% 45,XO) and age-matched, normal girls. A total of 137 girls with Turner syndrome and 70 normal girls had lipid profile measurements, including cholesterol, high-density lipoprotein cholesterol, and triglycerides. Older girls with Turner syndrome (> 11.0 years) had increased cholesterol levels (p < 0.01), compared with control values (190 +/- 38 vs 165 +/- 26 mg/dl). Cholesterol levels were elevated in older subjects with Turner syndrome versus normal subjects, after adjustment for age, karyotype, and body mass index z score effects (p = 0.01). In the subjects with Turner syndrome but not the normal subjects, serum cholesterol values correlated with age, weight, and body mass index z score (p < 0.02). We conclude that adolescent girls with untreated Turner syndrome have significantly increased cholesterol levels, independent of age, body mass index z score, or karyotype, and that these precede any treatment with exogenous estrogen or growth hormone.

Adventitious regeneration of Juglans nigra L. (eastern black walnut).

Somatic embryos and adventitious shoots were initiated from immature cotyledons 10-14 weeks after anthesis. Maximum embryogenesis occurred 12 weeks after anthesis and maximum shoot organogenesis occurred 14 weeks after anthesis. The best treatment for induction of somatic embryos and adventitious shoots from immature cotyledon explants was on agar-solidified WPM supplemented with 0.1 µM 2,4-D and 5.0 µM TDZ and incubated in light for the first four weeks. Rooting of adventitious shoots was best if they were quickdipped in 2.5 mM IBA and 1.25 mM NAA in 1% dimethyl formamide and 3.9% ethanol (1∶20 Wood's Rooting Compound: water, by volume). Plantlets from rooted adventitious shoots were acclimatized to the greenhouse.

Endoscopic and ultrasonographic observation of the canine prostate after transurethral balloon laser therapy (PROSTALASE).

We investigated the healing process and changes in the canine prostate after transurethral balloon-equipped laser (PROSTALASE) prostatectomy using both endoscopy and transrectal ultrasonography (TRUS). On TRUS, the prostate volume was significantly increased (123%) just after irradiation, decreasing to 106% at 1 week. Cavity formation was observed in the prostate 1 week after irradiation, and the median volume was 1.5 cm3 at 4 weeks. A TRUS study performed immediately after irradiation revealed a 1- to 2-mm deep hyperechoic lesion around the urethra. Urethrocystoscopy disclosed red and markedly edematous mucosa of the prostatic urethra, but no hemorrhage. The hyperechoic mass was also observed in the cavity on TRUS images 1 week later. Urethrocystoscopy disclosed abundant necrotic tissue within the cavity, and reddish granulomatous sections were observed on a portion of the cavity surface. At 4 weeks, the hyperechoic mass in the cavity was no longer observed on TRUS images. The prostate parenchyma was thin but uniformly isoechoic. At urethrocystoscopy, a smooth surface without redness and with the small craters, which were histologically identified as the duct openings of the prostate gland, were observed.

Prostatectomy by transurethral balloon Laserthermia (PROSTALASE) in the canine.

Prostatectomy by transurethral balloon Laserthermia (PROSTALASE) was performed in a canine model. This balloon device monitored by transrectal ultrasound can cylindrically irradiate with a laser beam. The treatment was performed in 8 canines using 15 watts for 20 minutes at 60 degrees C at a 5 mm depth of the prostate from the urethral surface. Immediately following the laser therapy, an area of coagulation necrosis was observed around the urethra to a depth of 4-5 mm from the surface. After 1 week, cavitation formation was seen in 3 or 4 canines by ultrasound, and the urethral reepithelialization was shown in 1 of 2 canines. After 2 weeks, cavitation formation was observed in both canines, and the urethra was completely reepithelialized in one canine. There was no tissue damage in the bladder neck of urethral sphincter and no urinary incontinence in any animal. This system is thought to be simple and, satisfactorily performed, is an effective transurethral prostatectomy.

Normal bone density of the wrist and spine and increased wrist fractures in girls with Turner's syndrome.

Turner's syndrome is associated with multiple skeletal abnormalities, including osteoporosis. We evaluated the hypothesis that girls with Turner's syndrome may have deficient bone density before the expected age of pubertal onset (9-13 yr) by comparing the bone mineral content of the wrist and lumbar spine in 78 girls with Turner's syndrome (4-13 yr old) and 28 normal prepubertal girls who were matched for age, bone age, body mass index, or height age. The bone mineral content of the wrist and spine was measured by single photon absorptiometry (SPA) and dual photon absorptiometry (DPA), respectively. SPA values for girls with Turner's syndrome vs. normal subjects (4-6.9, 7-9.9, and 10-12.9 yr old) were (mean +/- SD) 0.27 +/- 0.05 vs. 0.36 +/- 0.05, 0.35 +/- 0.06 vs. 0.41 +/- 0.06, and 0.41 +/- 0.05 vs. 0.45 +/- 0.03 g/cm2, respectively. SPA values in the Turner's syndrome girls were decreased compared to those in normal prepubertal girls, matched for age (P less than 0.0001), bone age, (P less than 0.001), and body mass index (BMI; P less than 0.0001), but not for height age. DPA values for girls with Turner's syndrome vs. normal girls in the same age categories were 0.65 +/- 0.06 vs. 0.70 +/- 0.09, 0.77 +/- 0.08 vs. 0.79 +/- 0.09, and 0.83 +/- 0.12 vs. 0.78 +/- 0.07 g/cm2. DPA values in Turner's syndrome girls (as a group) were decreased compared to those in normal prepubertal girls matched for age (P less than 0.05) and BMI (P less than 0.02), but not for bone age or height age. The annual incidence rate of wrist fractures in Turner's syndrome girls (9.1 of 1000) was significantly increased compared to the reported annual incidence rate in normal children (3.5 of 1000; P less than 0.003). We conclude that prepubertal-aged girls with Turner's syndrome (less than 13 yr old) have normal bone density for height age, but significantly decreased bone density of the wrist for chronological age, bone age, and BMI. They also have significantly more wrist fractures than normal girls, but it is not clear that this is related to their bone density.

The effect of short term treatment with growth hormone and ethinyl estradiol on lower leg growth rate in girls with Turner's syndrome.

An important consequence of Turner's syndrome is short stature. We previously reported that the optimal doses of ethinyl estradiol (EE2) and GH for the stimulation of short term growth in such patients were 100 ng/kg.day and 0.15 U/kg (administered sc three times weekly), respectively. The aim of this study was to determine whether the combination of low dose estrogen and GH would stimulate short term growth more than either agent administered alone. Thirty-nine girls with Turner's syndrome (aged 5-15 yr) underwent one to three 6-month cycles, each consisting of a 2-month baseline period, a 2-month treatment period, and a subsequent 2-month washout period. During the first 2 yr of the study, the girls were assigned to receive the three treatments in random order. The treatments were EE2 (100 ng/kg.day, orally), GH (0.15 U/kg, sc, three times weekly), or the combination of EE2 and GH. Subsequently, some of the girls were treated with reduced doses of EE2 (50 ng/kg.day) and GH [0.09 U/kg, three times weekly (tid)] according to the same protocol. Lower leg length was measured every 2 months throughout the study. EE2 increased lower leg growth rate significantly at the dose of 100 ng/kg.day, but not at the dose of 50 ng/kg.day. Similarly, the higher dose of GH (0.15 U/kg, tiw) increased lower leg growth rate significantly, whereas the lower dose (0.09 U/kg, tiw) did not. However, combined treatment with the lower doses of EE2 (50 ng/kg.day) and GH (0.09 U/kg, tiw) stimulated lower leg growth rate significantly and to a similar degree as the higher dose of GH (0.15 U/kg, tiw). This higher dose of GH appeared to cause a maximal increase in lower leg growth rate, which was not further increased by combined administration with the higher dose (100 ng/kg.day) of estrogen. Thus, addition of low dose EE2 to an optimal dose of GH did not cause any apparent increase in short term lower leg growth rate in girls with Turner's syndrome. Whether the long term outcome of GH treatment would be altered by concurrent administration of low dose estrogen will require long term clinical trials.

Effect of low doses of estradiol on 6-month growth rates and predicted height in patients with Turner syndrome.

We randomly assigned 16 girls with Turner syndrome, age 5 to 15 years, to receive treatment with 100 ng/kg/day ethinyl estradiol or placebo for 6 months, with crossover after a 2-month interim period. We assessed growth by measurement of the 4-week lower leg growth rate and by height velocity. Bone age was determined at the beginning and end of treatment. Growth rate during ethinyl estradiol treatment was approximately 70% greater than during placebo (P less than 0.001), without any bone age advancement relative to that with placebo. The change in predicted height was significantly greater after 6 months treatment with ethinyl estradiol than after treatment with placebo (mean +/- SEM, +0.35 +/- 0.38 cm vs. -0.85 +/- 0.32 cm, P less than 0.03). Breast budding occurred in six patients. We conclude that it may be feasible to begin low-dose estrogen therapy to promote growth at an earlier age than would be conventionally used to induce pubertal development. These data are still relatively short term, however; until long-term data are available, it would be premature to make definitive recommendations regarding the dose and timing of estrogen treatment in Turner syndrome.

Growth response relationship between growth hormone dose and short term growth in patients with Turner's syndrome.

Short stature is a common feature of Turner's syndrome. We studied the dose-response relationship between short term linear growth and GH dose using the lower leg-measuring device. Three doses of GH (0.05, 0.15, and 0.45 U/kg, three times weekly) were given sc for 1-month treatment periods. Lower leg growth rate increased significantly during treatment with the 0.15 and 0.45 U/kg doses [1.8 +/- 0.2 (+/- SEM) and 1.7 +/- 0.3 mm/4 weeks). The higher dose of 0.45 U/kg was no more effective than the 0.15 U/kg dose. Serum somatomedin-C levels increased after treatment with each of the three doses of GH, but did not differ in any of the three dosage groups. We conclude that 0.15 U/kg GH, three times weekly, stimulates short term growth in patients with Turner's syndrome. Longer term studies are required to determine if this increased growth rate is sustained.

Growth hormone secretory dynamics in Turner syndrome.

We investigated whether a decrease in serum growth hormone contributes to the short stature of adults with Turner syndrome by measuring the 24-hour profile of serum growth hormone in 30 patients aged 2 to 20 years. Growth hormone pulses were defined as a rise from nadir to peak that exceeded three times the intraassay coefficient of variation. Girls with Turner syndrome aged 2 to 8 years did not have statistically different growth hormone levels, peak amplitudes, and peak frequencies compared with those in age-matched controls. By contrast, girls with Turner syndrome aged 9 to 20 years had significantly decreased mean 24-hour growth hormone levels, peak amplitudes, and peak frequencies compared with those in age-matched normal girls. Patients with Turner syndrome of all ages had decreased serum somatomedin-C concentrations and delayed bone ages. We conclude that a relative deficiency of growth hormone in pubertal patients with Turner syndrome may contribute to their adult short stature.

Estimation of actual caries prevalence and treatment needs from field survey caries information on a child population in U.S.A.

Caries scores (DT + Dt) were recorded under simulated field survey conditions on 270 children ranging in age from 3 to 12 years. The children were subsequently diagnosed under optimum clinical conditions. The findings from the field and clinical examinations were statistically analyzed to determine the relationships between "survey" and "true" caries scores. It is proposed that the true mean caries score can be estimated from the survey mean score by adding 1.5 teeth in the primary dentition and 2 teeth in the mixed dentition. Tables were devised to estimate treatment needs for children at various survey caries scores in each dentition category.