Clinical standards for the diagnosis and management of asthma in low- and middle-income countries.

BACKGROUND: The aim of these clinical standards is to aid the diagnosis and management of asthma in low-resource settings in low- and middle-income countries (LMICs).METHODS: A panel of 52 experts in the field of asthma in LMICs participated in a two-stage Delphi process to establish and reach a consensus on the clinical standards.RESULTS: Eighteen clinical standards were defined: Standard 1, Every individual with symptoms and signs compatible with asthma should undergo a clinical assessment; Standard 2, In individuals (>6 years) with a clinical assessment supportive of a diagnosis of asthma, a hand-held spirometry measurement should be used to confirm variable expiratory airflow limitation by demonstrating an acute response to a bronchodilator; Standard 3, Pre- and post-bronchodilator spirometry should be performed in individuals (>6 years) to support diagnosis before treatment is commenced if there is diagnostic uncertainty; Standard 4, Individuals with an acute exacerbation of asthma and clinical signs of hypoxaemia or increased work of breathing should be given supplementary oxygen to maintain saturation at 94-98%; Standard 5, Inhaled short-acting beta-2 agonists (SABAs) should be used as an emergency reliever in individuals with asthma via an appropriate spacer device for metered-dose inhalers; Standard 6, Short-course oral corticosteroids should be administered in appropriate doses to individuals having moderate to severe acute asthma exacerbations (minimum 3-5 days); Standard 7, Individuals having a severe asthma exacerbation should receive emergency care, including oxygen therapy, systemic corticosteroids, inhaled bronchodilators (e.g., salbutamol with or without ipratropium bromide) and a single dose of intravenous magnesium sulphate should be considered; Standard 8, All individuals with asthma should receive education about asthma and a personalised action plan; Standard 9, Inhaled medications (excluding dry-powder devices) should be administered via an appropriate spacer device in both adults and children. Children aged 0-3 years will require the spacer to be coupled to a face mask; Standard 10, Children aged <5 years with asthma should receive a SABA as-needed at step 1 and an inhaled corticosteroid (ICS) to cover periods of wheezing due to respiratory viral infections, and SABA as-needed and daily ICS from step 2 upwards; Standard 11, Children aged 6-11 years with asthma should receive an ICS taken whenever an inhaled SABA is used; Standard 12, All adolescents aged 12-18 years and adults with asthma should receive a combination inhaler (ICS and rapid onset of action long-acting beta-agonist [LABA] such as budesonide-formoterol), where available, to be used either as-needed (for mild asthma) or as both maintenance and reliever therapy, for moderate to severe asthma; Standard 13, Inhaled SABA alone for the management of patients aged >12 years is not recommended as it is associated with increased risk of morbidity and mortality. It should only be used where there is no access to ICS.The following standards (14-18) are for settings where there is no access to inhaled medicines. Standard 14, Patients without access to corticosteroids should be provided with a single short course of emergency oral prednisolone; Standard 15, Oral SABA for symptomatic relief should be used only if no inhaled SABA is available. Adjust to the individual's lowest beneficial dose to minimise adverse effects; Standard 16, Oral leukotriene receptor antagonists (LTRA) can be used as a preventive medication and is preferable to the use of long-term oral systemic corticosteroids; Standard 17, In exceptional circumstances, when there is a high risk of mortality from exacerbations, low-dose oral prednisolone daily or on alternate days may be considered on a case-by-case basis; Standard 18. Oral theophylline should be restricted for use in situations where it is the only bronchodilator treatment option available.CONCLUSION: These first consensus-based clinical standards for asthma management in LMICs are intended to help clinicians provide the most effective care for people in resource-limited settings.

Increased aggression and lack of maternal behavior in Dio3-deficient mice are associated with abnormalities in oxytocin and vasopressin systems.

Thyroid hormones regulate many aspects of brain development and function, and alterations in the levels of thyroid hormone action lead to abnormal anxiety- and depression-like behaviors. A complement of factors in the brain function independently of circulating levels of hormone to strictly controlled local thyroid hormone signaling. A critical factor is the type 3 deiodinase (DIO3), which is located in neurons and protects the brain from excessive thyroid hormone. Here, we examined whether a local increase in brain thyroid hormone action secondary to DIO3 deficiency is of consequence for social behaviors. Although we did not observe alterations in sociability, Dio3-/- mice of both sexes exhibited a significant increase in aggression-related behaviors and mild deficits in olfactory function. In addition, 85% of Dio3-/- dams manifested no pup-retrieval behavior and increased aggression toward the newborns. The abnormal social behaviors of Dio3-/- mice were associated with sexually dimorphic alterations in the physiology of oxytocin (OXT) and arginine vasopressin (AVP), 2 neuropeptides with important roles in determining social interactions. These alterations included low adult serum levels of OXT and AVP, and an abnormal expression of Oxt, Avp and their receptors in the neonatal and adult hypothalamus. Our results demonstrate that DIO3 is essential for normal aggression and maternal behaviors, and indicate that abnormal local regulation of thyroid hormone action in the brain may contribute to the social deficits associated with neurodevelopmental disorders.

Phytoremediation and removal mechanisms in Bouteloua curtipendula growing in sterile hydrocarbon spiked cultures.

Tolerance index and phytoremediation factors of side oats grama (Bouteloua curtipendula) with recalcitrant polycyclic aromatic hydrocarbons (PAH) phenanthrene (PHE), pyrene (PYR), and benzo[a]pyrene (BaP) and the resulting impact on phenotypic response, were evaluated in sterile conditions with whole plant growing in test-tube cultures with MS medium with PAH and compared with Tall fescue (Festuca arundinacea), control for this study. PAH mixture of PHE, PYR and BaP (1:1:1 w/w/w) blended with Maya crude oil (1:1 w/w), final concentration of 1500 mg kg(-1) was used. After 40 days, BaP removal, in the presence of Maya crude was superior compared with PHE and PYR removal Although the presence of PAH negatively affects the phenotypic response of the plants; sterile conditions experiments were helpful to evaluate phytoremediation factors to elucidate some important questions regarding phytoremediation mechanisms; in this study, B. curtipendula was able to phytostabilizate BaP associated to a significant hydrocarbon removal (57.4%) with high root accumulation but attenuated transport to stems, here reported as translocation factor. To our knowledge, this is the first time that quantifiable phytoremediation factors were used to evaluate the tolerance and removal capacity of a native semi-arid climate plant which is probably able to phytoremediate hydrocarbon contaminated soils.

Effect of zinc upon human and murine cell viability and differentiation.

Most zinc studies show its benefits or changes that coincide with its deficiency, but some have reported damages by supplements. In this work, the effects of zinc in different cell lines (U-937, human monocytes, and murine bone marrow cells) were analyzed. The cells were put in their specific culture medium either alone or with a stimulant [1-phorbol 12-myristate 13-acetate (PMA) for U-937 and monocytes, granulocyte macrophage colony stimulating factor (GM-CSF) for bone marrow cells]. These preparations, with or without zinc (0.05 to 1.0 mM), were incubated and microscopically analyzed on days 3, 9, and 11. The viability of all cells cultivated with 0.05 and 0.1 mM of zinc was similar to that of the controls without zinc (90%). With 1.0 mM of zinc, the viability diminished (p < 0.005) to 80% in U-937 and to 50% in monocytes and bone marrow cells; the number of cells increased in the three lines, but there was no differentiation. We conclude that the effects observed with different doses of zinc vary not only among the different species but also according to the time the cells were exposed to the metal. The same doses of zinc can have either a stimulatory or an inhibitory effect.

Alumina particles influence the interactions of cocultured osteoblasts and macrophages.

The purpose of the current study was to evaluate the effects of alumina particles on secretion of several cytokines involved in bone resorption in cocultures of macrophages and osteoblasts. To distinguish the contribution of each individual cell type, we have established a heterologous in vitro system that makes use of mouse J774 cells and primary cultured human osteoblasts. J744 cells decreased the production of TNF-alpha when they were cocultured with osteoblasts. Treatment of J744 cells with alumina particles increased TNF-alpha secretion, but the induction was lower when cells were cocultured with osteoblasts. Secretion of IL-6 by J744 cells was very low, and increased in the presence of osteoblasts. Alumina particles were only able to stimulate the release of IL-6 by J744 cells when cells were cocultured with osteoblasts. On the other hand, incubation of osteoblasts with alumina particles enhanced the release of IL-6 and GM-CSF. Coculturing osteoblasts with J744 cells induced them to release IL-6 and GM-CSF, and treatment with alumina further increased the secretion of both mediators by osteoblasts. According to these in vitro results, it seems rather plausible that alumina particles are able to initiate an inflammatory response in vivo.

Abnormalities in the bone mineral metabolism in HIV-infected patients.

OBJECTIVE: To evaluate bone mineral metabolism in HIV infected and asymptomatic patients receiving highly active antiretroviral therapy (HAART) containing protease inhibitors (PI) and naïve patients. METHODS: We studied 30 asymptomatic HIV infected male patients, 13 in the naive group and 17 in the IP group, both without differences in demographics characteristics. We excluded women and patients with any known factor associated to osteopenia. We did a nutritional questionnaire, a DEXA scan in lumbar spine and femur, a study of CD4 lymphocytes, viral load and an analysis of bone formation and resorption markers in all patients. We compared vitamin D and PTH levels with a control group of healthy male volunteers age-pareated. For the statistical analysis we used the SPSS program. RESULTS: Osteopenia was present in 17/30 (57%), 8/13 (61.5%) in the naïve group and 9/17 (53%) in the PI group (not significant differences). We found a vitamin D deficiency in 86% of patients, with mean serum levels that was found to be significantly lower than those from a healthy control group (p=0.04). Testosterone level was significantly related to bone mineral density in lumbar spine (p

Improvement of the hydrocarbon phytoremediation rate by Cyperus laxus Lam. inoculated with a microbial consortium in a model system.

Hydrocarbon phytoremediation by Cyperus laxus Lam. growing on perlite and inoculated with hydrocarbon-degrading microorganisms was evaluated. Total petroleum hydrocarbons (TPH) were extracted from weathered soil (60.7 g of TPH kg(-1) of dry soil) and spiked on perlite at initial concentration of 5 g of TPH kg(-1) of dry perlite. Phenological characteristics, total microbial viable counts, hydrocarbon degraders and residual hydrocarbons were determined through 180 days of culture. Phenological characteristics of inoculated plants were improved as compared with non-inoculated plants: root biomass was 1.6 times greater, flowering time was reduced (13%), and the number of inflorescences was 1.5 times higher. The rhizospheric bacterial and fungi counts were higher for planted treatments (inoculated and not inoculated) than for unplanted pots. The maximum phytoremediation rate (0.51 mg of TPH g(-1) of dry plant d(-1)) for inoculated plants was reached at 60 days of culture, and was two times higher than for non-inoculated plants (55% TPH removal). Similar hydrocarbon phytoremediation extent values for inoculated (90%) and non-inoculated (85%) plants were obtained at 180 days of culture. The present study demonstrated that mutual benefits between C. laxus and inoculated hydrocarbon-degrading microorganisms are improved during phytoremediation. It is pertinent to note that this is the first report of hydrocarbon phytoremediation by Cyperus laxus Lam., a native plant growing in highly contaminated swamps.

Sexualidad y afectividad en el climaterio / Sexuality and affective relationship during the climateric

Se analizan los cambios que se pueden producir en la sexualidad durante el climaterio. Se revisan la valoración, los diagnósticos y los cuidados de enfermería relacionados con el patrón de sexualidad y se proponen estrategias prácticas de acción desde un modelo integral (AU)

Effects of polyethylene and alpha-alumina particles on IL-6 expression and secretion in primary cultures of human osteoblastic cells.

The effect of two biomaterials, polyethylene and alpha-alumina, on interleukin-6 (IL-6) secretion and expression has been studied in human osteoblasts in primary culture. Human osteoblastic cells were derived from fresh trabecular bone explants removed during total knee arthroplasty. On reaching confluence, cells were subcultured in 6 well plates; the resulting subcultures were incubated until confluence and polyethylene or alpha-alumina particles were added to some while the rest were left as controls. The IL-6 mRNA levels were assessed by reverse transcription (RT) followed by polymerase chain reaction (PCR). IL-6 secretion was measured in the conditioned medium. The IL-6 expression was higher in the presence of both biomaterials. Maximum expression occurred in response to a dose of 50 mg particles well with both biomaterials and was greater after polyethylene particle addition than after alpha-alumina particle addition at this dose. The maximum IL-6 secretion elicited by alpha-alumina was produced at 10 mg particles well while maximum response with polyethylene required 50 mg well. At a dose of 10 mg/well, alpha-alumina particles induced more secretion than 10 mg of polyethylene particles. Nevertheless, at a dose of 50 mg/well maximum secretion was produced with polyethylene particles. In conclusion and in our experimental conditions, polyethylene as well as alpha-alumina increased both the expression and the secretion of IL-6 in human osteoblastic cells in primary culture and stimulation from polyethylene appears stronger than that from alpha-alumina at the same dose.

Effects of MA 956 superalloy and alpha-alumina particles on some markers of human osteoblastic cells in primary culture.

One of the problems associated with the modern biomaterials used in prostheses is osteolysis, which, although its exact origin is unknown, has been associated with wear particles. Osteoblasts seem to participate directly in this phenomenon. This paper investigates in vitro cellular response to the wear particles from the metal substrate and ceramic covering (alpha-alumina) of a new titanium yttrium aluminum alloy, MA 956, that has been proposed as a biomaterial because of its exceptional mechanical and electrochemical properties. The effect of different sizes (10 and 80 microm) of MA 956 and alpha-alumina particles on osteoblast function was studied in primary human bone cell cultures. Cells were harvested from trabecular bone fragments obtained during knee arthroplasty. Osteoblastic cell response to the particles was measured by assaying C-terminal type I procollagen (PICP), alkaline phosphatase, and osteocalcin secretion, with and without 1.25(OH)(2)D(3) stimulation, in the cell-conditioned medium. Both sizes of MA 956 and alpha-alumina particles decreased PICP secretion in nonstimulated osteoblastic cells, but this secretion was not affected in the cultures stimulated with 1.25(OH)(2)D(3). Only the 10 microm alpha-alumina particles inhibited alkaline phosphatase activity in 1.25(OH)(2)D(3)-stimulated and nonstimulated cultures. The rise in osteocalcin levels after 1.25(OH)(2)D(3) stimulation was lower in the presence of the 10 microm MA 956 particles than in the presence of alpha-alumina particles. Although both materials seem to have directly affected in vitro osteoblastic cell function, the increase in osteocalcin levels after 1.25(OH)(2)D(3) stimulation was lower after exposure to MA 956 particles than the increase observed after exposure to alpha-alumina particles. Therefore, it does not seem that osteocalcin stimulated bone resorption, suggesting that MA 956 would be less likely to provoke osteolysis.

Low vitamin D levels in outpatient postmenopausal women from a rheumatology clinic in Madrid, Spain: their relationship with bone mineral density.

To evaluate a possible relationship between vitamin D levels and bone mineral density (BMD) and the prevalence of hypovitaminosis in a population of postmenopausal women from a rheumatologic outpatient clinic in Madrid, Spain, 171 postmenopausal women (aged 47-66 years) divided into two groups (osteoporotic and nonosteoporotic, according to WHO criteria) were studied between November and June. Liver and kidney function were normal in all subjects. Serum parathyroid hormone (PTH) and calcidiol levels were determined and bone densitometry carried out at the lumbar spine and hip level. PTH and calcidiol serum levels did not show any correlation. Serum PTH was inversely related to BMD at both hip and lumbar spine in the total group, and at the hip with calcidiol levels lower than 37 nmol/l. Calcidiol was directly related to hip BMD only when levels were lower than 37 nmol/l. Results of a stepwise multiple regression analysis showed that the single factor which affected BMD at the hip was calcidiol in the subgroup with serum calcidiol levels below 37 nmol/l, while in the subgroup with serum calcidiol levels above 37 nmol/l, the main factor affecting hip BMD was serum PTH. The prevalence of vitamin D deficiency at a cutoff of 37 nmol/l was 64%. In summary, calcidiol serum levels below 37 nmol/l seem to affect bone mass, regardless of the effect of PTH. Vitamin D deficiency is a frequent finding in the postmenopausal women who attend a rheumatology outpatient clinic in Madrid. Vitamin D supplementation should therefore be considered in this population during the winter season.

Reliability and validity of a self-administered food frequency questionnaire in a chemoprevention trial of adenoma recurrence.

Various chemoprevention trials have assessed dietary intake by means of food frequency questionnaires. However, it is important to assess the degree to which such questionnaires can measure diet. We conducted reproducibility and validity analyses of our Arizona Food Frequency Questionnaire (AFFQ) in our recently completed, randomized, Phase III chemoprevention trial testing the effects of a wheat bran fiber supplement on colorectal adenoma recurrence. A total of 139 individuals provided a baseline and year 1 AFFQ and a set of 4-day dietary records collected over a period of 1 month. The reproducibility analyses of the AFFQ administered 1 year apart showed a mean intraclass correlation of 0.54 for unadjusted nutrients and 0.48 for energy-adjusted nutrients. The relative validity of the AFFQ, as compared with the average of the 4-day diet records, showed a mean deattenuated correlation of 0.49 (range, 0.22-0.65) for the baseline AFFQ and 0.49 (range, 0.25-0.67) for the year 1 AFFQ. When data from both AFFQs were combined and compared with the diet records, there was a slight improvement in the overall deattenuated correlations (mean, 0.56; range, 0.33-0.71). The correlations we observed for macro- and micronutrient intake were within the overall range of those reported in the literature. Reliability and validity studies of dietary instruments are feasible in the setting of a chemoprevention trial and should be conducted when the instrument's performance has not been previously assessed in the target population.

Risk factors for Ki-ras protooncogene mutation in sporadic colorectal adenomas.

The Ki-ras protooncogene frequently is mutated in colorectal adenocarcinomas, but the etiology of this molecular event is uncertain. We investigated the association between variables known or suspected to be related to risk for colorectal cancer and the occurrence of Ki-ras mutations in colorectal adenomas. This study was conducted among 678 male and female participants, 40-80 years of age, enrolled in a phase III trial testing the effects of a wheat bran fiber supplement on adenoma recurrence. Exposure information on the risk factors of interest was assessed through self-administered questionnaires. Mutations in codons 12 and 13 of the Ki-ras protooncogene were analyzed in baseline adenomas 0.5 cm or larger by PCR amplification followed by direct sequencing. Eighteen percent (120 of 678) of the participants had one or more adenoma(s) with Ki-ras mutations. A higher risk of Ki-ras mutations was associated with increasing age and a lower intake of total folate. The odds ratio (OR) for Ki-ras mutations for individuals >72 years of age was 1.98 [95% confidence interval (CI) = 1.19-3.27; P for trend = 0.008] compared with those less than 65 years of age. Compared with individuals in the lower tertile of total folate, those in the upper tertile had an approximately 50% lower risk of having Ki-ras mutation-positive adenomas (OR = 0.52; 95% CI = 0.30-0.88; P for trend = 0.02). There was a suggestion of a stronger inverse association of total folate with G-->T transversions (OR = 0.41; 95% CI = 0.20-0.87) than G-->A transitions (OR = 0.61; 95% CI = 0.31-1.21), although the CIs for the associations overlap. The results of these analyses suggest that the protective effect of folate in colon cancer observed in published studies may be mediated through folate's effect on Ki-ras mutations.

Reduced nicotinamide adenine dinucleotide phosphate-diaphorase activity in the paraventricular nucleus of the rat hypothalamus is modulated by estradiol.

Based on previous studies demonstrating that reduced nicotinamide adenine dinucleotide phosphate (NADPH)-diaphorase (ND) activity is modulated by estradiol and the discovery of a new subtype of estrogen receptor highly expressed in the paraventricular nucleus of the hypothalamus (PVN), a possible estrogen influence on this activity was investigated in the neuronal populations (magno- and parvicellular) of this nucleus. Cryostat sections were cut and processed for the histochemical detection of the ND activity. Following ovariectomy (14 days), numerical data displayed a slight decrease in the number of ND-neurons, especially in the posterior magnocellular and the medial parvicellular subdivisions, which was reversed after daily treatment with estradiol benzoate. Administration of estradiol benzoate to male rats (14 days) induced a significant increase (P < 0.05) in the number of ND-neurons, mainly at the level of the posterior magnocellular subdivision. These data indicate that paraventricular ND-neurons are influenced by estradiol.

Effect of 25-OH-vitamin D on fracture healing in elderly rats.

To investigate the effect of 25-OH-vitamin D supplements (calcidiol) on fracture healing in the elderly, an experimental model with 15 18-month-old female Wistar rats was designed. An experimental fracture in the middle third of both femora of each rat was made. Then the rats were randomly assigned to two groups: one group was subcutaneously treated with 25-OH-vitamin D during all healing processes, and the other group (the control group) was not. After 5 weeks of healing, the animals were killed and both femora were extracted. Blood samples were collected before fracture and at death to determine the levels of 25-OH-vitamin D. All bones that were extracted were subjected to a torsion test to assess healing; a significantly greater maximum shear force before failure was supported in the treated group (p < 0.01). Moreover, a positive correlation (p < 0.01; r=0.55) was found between blood levels of 25-OH-vitamin D at death and the mechanical strength of the callus. Thus, the administration of 25-OH-vitamin D after the experimental fracture significantly improved the mechanical strength of the fractured bone. If similar results are found in the human, then treatment with 25-OH-vitamin D after the occurrence of a fracture would be a good way to improve fracture healing in the elderly.

Olive oil and human cancer: an assessment of the evidence.

BACKGROUND: We have attempted to summarize the evidence concerning the association of olive oil intake with cancer risk in humans. METHODS: We reviewed all the studies that met the following criteria: (1) they have directly examined olive oil in the context of an extensive food frequency questionnaire or have evaluated the role of monounsaturated fat in populations of Mediterranean countries where a large fraction of monounsaturated fat originates from olive oil and (2) they have analyzed the data with explicit or implicit control for energy intake to accommodate the likely confounding influence of caloric consumption and to account to a certain extent for differential completeness of reporting between cases and controls. Ecologic studies were also considered and relevant experimental data were invoked. RESULTS: With respect to breast cancer, there is converging evidence for a protective effect, although the data are not definitive. For other cancer types, the overall epidemiologic evidence, although promising, is quantitatively limited and qualitatively suboptimal. CONCLUSIONS: The issue is of major public health importance and deserves additional study.

Frequent recurrence of secondary hyperparathyroidism after pulse oral calcitriol withdrawal in PD patients.

The aim of this study was to evaluate the role of pulse oral calcitriol in the control of secondary hyperparathyroidism in peritoneal dialysis (PD) patients, addressing the effects after withdrawal. We studied 15 patients with intact parathyroid hormone (iPTH) plasma levels above 250 pg/mL. The initial calcitriol dose was 8 or 4 micrograms/week, administered in two doses, according to whether the iPTH plasma levels were above or below 400 pg/mL. This dose was modified during the follow-up according to the response. Serum iPTH levels decreased in all patients after the first month (559 +/- 243 to 212 +/- 94 pg/mL, p < 0.001). Serum calcium levels significantly increased during therapy, while serum phosphorus levels did not change. The mean duration of the treatment was 95 +/- 57 days. Nine patients reached the target iPTH levels without complications, and in 6 patients the treatment was interrupted because of hypercalcemia. One month after finishing pulse therapy, a significant decrease in serum calcium levels and an increase in iPTH levels were observed. These values were similar to baseline data and were significantly higher than those found during the pulse calcitriol period. Pulse oral calcitriol administration seems to be a short-term, efficient therapy for secondary hyper-parathyroidism in PD patients. However, after the end of pulse therapy, iPTH serum levels return to baseline values, suggesting long-term therapeutic failure.

Calcium, vitamin D, and the occurrence of colorectal cancer among women.

BACKGROUND: Despite evidence from animal studies for a protective effect of higher calcium and possibly vitamin D intake against colorectal cancer, epidemiologic studies have been inconclusive. PURPOSE: We investigated the associations between the intake of calcium and vitamin D and the occurrence of colorectal cancer. METHODS: In a prospective study, 89 448 female registered nurses who were free of cancer responded to a mailed, semiquantitative food-frequency questionnaire in 1980; dietary information was updated in 1984 and 1986. Through 1992, 501 incident cases of colorectal cancer (396 colon and 105 rectal cancers) were documented. As measures of exposure, we used nutrient intake in 1980 and also two measures of long-term intake on the basis of the three questionnaires: the average of intakes from the three questionnaires and consistent intakes, which were defined as high if women were in the upper tertile on all questionnaires and low if they were in the lower tertile on all questionnaires. To further characterize long-term intake, we conducted analyses excluding women who reported a change in their consumption of milk (primary source of calcium and vitamin D) in the 10 years prior to 1980. Relative risks (RRs) and 95% confidence intervals (CIs) were calculated using the lowest quintile of intake as a reference. The Mantel extension test was used to evaluate linear trends across the categories of nutrient intake. In multivariate analyses, the trends were tested with use of the medians of the intake as a continuous variable in the logistic model. The P values for the trends were two-sided. RESULTS: On the basis of the data from the 1980 questionnaire alone, the multivariate RR for colorectal cancer for women in the upper versus the lower quintile were 0.80 (95% CI = 0.60-1.07) for dietary calcium, 0.84 (95% CI = 0.63-1.13) for dietary vitamin D (from foods only), and 0.88 (95% CI = 0.66-1.16) for total vitamin D (from foods and supplements). After the exclusion of women who reported a change in their milk intake, the RRs for colorectal cancer for the highest versus the lowest categories of average intake were 0.74 (95% CI = 0.36-1.50) for dietary calcium, 0.72 (95% CI = 0.34-1.54) for dietary vitamin D, and 0.42 (95% CI = 0.19-0.91) for total vitamin D. The corresponding RRs for the consistency analyses were 0.70 (95% CI = 0.35-1.39) for dietary calcium, 0.59 (95% CI = 0.30- 1.16) for dietary vitamin D, and 0.33 (95% CI = 0.16-0.70) for total vitamin D. CONCLUSIONS: These findings do not support a substantial inverse association between calcium intake and risk of colorectal cancer, but an inverse association between intake of total vitamin D and risk of colorectal cancer was suggested. IMPLICATIONS: Available evidence does not warrant an increase in calcium intake to prevent colon cancer, but longer-term studies of both calcium and especially vitamin D in relation to colorectal cancer risk are needed.

The interaction of PTH and dietary phosphorus and calcium on serum calcitriol levels in the rat with experimental renal failure.

BACKGROUND: Renal failure results in decreased calcitriol production, a key factor in the development of secondary hyperparathyroidism. Phosphorus accumulation and high parathyroid hormone (PTH) levels, both inherent to renal failure, have different effects on calcitriol production; moreover, dietary calcium loading may have a separate inhibitory effect on calcitriol production. This study was designed to evaluate the relative effects of PTH and dietary phosphorus and calcium on serum calcitriol levels. METHODS: Renal failure was surgically induced and rats were divided into normal, moderate renal failure, and advanced renal failure based on the serum creatinine. Each group was subdivided and received either a high-phosphorus diet (HPD, 0.6% Ca, 1.2% P) or high-calcium diet (HCaD, 1.2% Ca, 0.6% P) for 14-16 days to determine the relative effects of dietary calcium and phosphorus loading on serum calcitriol. In addition the effect of PTH and phosphorus on calcitriol stimulation was determined with a 48-h PTH infusion combined with either a low (0.16%) or high (1%) phosphorus diet; both diets had negligible calcium (< 0.05%). RESULTS: With decreasing renal function, PTH increased and was greater in rats fed the HPD than the HCaD; serum calcitriol decreased as renal function decreased and was lower in normal rats and rats with moderate renal failure fed a HCaD (P < 0.01). The calcitriol response to a PTH infusion decreased as renal function decreased (P < 0.05) but was greater on a low- (0.16%) than a high- (1%) phosphorus diet (P < 0.05). CONCLUSIONS: Dietary calcium loading either directly decreases serum calcitriol or acts by modifying the stimulatory effect of PTH; the stimulatory effect of PTH on serum calcitriol is modified by dietary phosphorus; in moderate renal failure, serum calcitriol levels depend on a complex interaction between PTH and dietary calcium and phosphorus; and in advanced renal failure, serum calcitriol levels are low and are difficult to stimulate, presumably because of the loss of renal mass.

Factors in the development of secondary hyperparathyroidism during graded renal failure in the rat.

Secondary hyperparathyroidism (2 degree HPT) develops as a result of renal failure. Hypocalcemia, phosphorus retention, calcitriol deficiency and skeletal resistance to the calcemic action of parathyroid hormone (PTH) are closely interrelated pathogenic factors important for the development of 2 degrees HPT in renal failure. Since previous studies have mainly focused on advanced renal failure, only limited data are available in early renal failure. The goal of the present study was to evaluate how alterations in the dietary calcium and phosphorus composition affect the factors known to contribute to the genesis of 2 degrees HPT in early and more advanced renal failure. To achieve this goal, graded differences in renal function were surgically induced in 453 rats while the dietary content of calcium and phosphorus was varied. Three different diets were used: (1) a high phosphorus diet (HPD), to induce phosphorus retention and stimulate 2 degrees HPT; (2) a high calcium diet (HCaD), to inhibit calcitriol synthesis; and (3) a moderate calcium-moderate phosphorus diet (MCaPD), to separate the effects of high dietary phosphorus and calcium. Based on the serum creatinine (SCr) concentration rats were assigned to one of four different groups: (1) normal renal function (SCr < or = 0.3 mg/dl); (2) mild renal failure (SCr 0.4 to 0.6 mg/dl); (3) moderate renal failure (SCr 0.7 to 0.8 mg/dl); or (4) advanced renal failure (SCr > or = 0.9 mg/dl). As the severity of renal failure increased, progressive 2 degrees HPT developed in each of the dietary groups.(ABSTRACT TRUNCATED AT 250 WORDS)