Baseline diet modifies the effects of dietary change.

The Dietary Approaches to Stop Hypertension (DASH) eating pattern has been shown to reduce blood pressure (BP) in previous clinical trials. In the PREMIER study, an established behavioural intervention, with or without DASH, promoted greater weight loss than an advice-only control group, but effects of the DASH intervention on BP were weaker. In these analyses, PREMIER data were used to evaluate whether change in dairy product or fruit and vegetable (FV) intake during the first six intervention months impacted changes in weight and/or BP. Study participants were classified as having low or high intakes of dairy products (<1·5 v. ≥1·5 servings/d) and FV (<5 v. ≥5 servings/d) at baseline and 6 months. For dairy products, in particular, participants with higher baseline intakes tended to decrease their intakes during the intervention. In these analyses, subjects consuming <1·5 dairy servings/d at baseline whose intake increased during the intervention lost more weight than those whose intake decreased or remained low throughout (10·6 v. 7·0 pounds (4·8 v. 3·2 kg) lost, respectively, P = 0·002). The same was true for FV intake (11·0 v. 5·9 pounds (5·0 v. 2·7 kg) lost, P < 0·001). We also found synergistic effects of dairy products and FV on weight loss and BP reduction. Specifically, subjects who increased their intakes of dairy products and also consumed ≥5 servings of FV/d lost more weight and had greater reductions in BP than other groups; in addition, higher FV intakes had the greatest benefit to BP among those consuming more dairy products. These results provide evidence that the DASH pattern was most beneficial to individuals whose baseline diet was less consistent with DASH.

Lean red meat consumption and lipid profiles in adolescent girls.

BACKGROUND: Epidemiological studies of red meat consumption often fail to distinguish between leaner and fattier or processed cuts of meat. Red meat has also been frequently linked with less healthy diet patterns. Data exploring the health effects of lean red meat in younger individuals are scarce, particularly in the context of a healthy diet. The present study examined the effects of lean red meat in combination with higher intakes of fruit/nonstarchy vegetables on lipid profiles in older adolescent girls. METHODS: Data from 1461 girls who were followed for 10 years, starting at 9-10 years of age, in the National Heart Lung and Blood Institute Growth and Health Study were used. Diet was assessed using multiple sets of 3-day records collected over eight examination cycles. Outcome measures included fasting levels of low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), non-HDL-C and triglycerides at age 18-20 years. RESULTS: After adjusting for age, race, socioeconomic status, height, activity level, hours of television per day, and intakes of whole grains and dairy foods using multivariable modelling, girls consuming ≥6 oz lean red meat per week combined with two or more servings of fruit/nonstarchy vegetables per day had LDL-C levels approximately 6-7 mg dL(-1) lower (P < 0.05) than girls with lower intakes of lean red meat and fruit/nonstarchy vegetables. In addition, girls with higher intakes of both were 33% less likely (odds ratio = 0.67, 95% confidence interval = 0.48-0.94) to have an LDL-C ≥110 mg dL(-1) and 41% less likely (odds ratio = 0.59, 95% confidence interval = 0.42-0.83) to have an elevated LDL : HDL ratio (≥2.2) at the end of adolescence. CONCLUSIONS: These analyses suggest that lean red meat may be included in a healthy adolescent diet without unfavourable effects on lipid values.

Functional properties of behaviour problems depending on level of intellectual disability.

BACKGROUND: Behaviour problems are common among individuals with intellectual disabilities (ID) especially in those with more severe forms. The determination of the functional profile of a targeted behaviour has important implications for the design of customised behavioural interventions. METHOD: We investigated the relationship between the level of ID and the functional profile of aggression, stereotypy and self-injurious behaviour (SIB) using the Questions about Behavioural Function (QABF). Two staff members at two time points completed the QABF for each of 115 adults with varying levels of ID participating in a day training and habilitation programme. RESULTS AND CONCLUSIONS: Our results suggest that there is a differential relationship between the functions of behaviour problems and level of ID. While SIB is more often seen by raters to be maintained by escape of social demands and by attaining access to tangible items with the decline of the intellectual level, aggressive and stereotypic behaviours were identified more often as serving multiple functions equally across functioning level.

Eating patterns and lipid levels in older adolescent girls.

BACKGROUND AND AIMS: Few studies have evaluated the effects of food-based eating patterns on adolescent lipid levels. This study examines whether usual adolescent eating patterns (ages 9-17 years) predict lipid levels at 18-20 years of age. METHODS AND RESULTS: This study uses previously collected data from the longitudinal NHLBI Growth and Health Study in which 2379 girls were enrolled at ages 9-10 years and followed for ten years. Food-based eating patterns were derived from multiple 3-day diet records. After adjusting for age, race, socioeconomic status, height, physical activity, and television viewing, girls with higher intakes of dairy, fruit and non-starchy vegetables had about a 40-50% reduced risk an LDL-C ≥ 170 mg/dL and non-HDL-C ≥ 145 mg/dL. Diets characterized by higher intakes of dairy and whole grains had similar benefits on TC and LDL-C. Girls consuming more fruits and non-starchy vegetables as well as more whole grains were much less likely to have high-risk lipid levels. Lean meat, poultry and fish when consumed in the context of other healthy eating patterns had no adverse effects on lipid levels in late adolescence. In fact when consumed with higher amounts of fruit and non-starchy vegetables, lean meat, poultry and fish had beneficial effects on HDL. Finally, dietary patterns that included more whole grains tended to be associated with lower TG levels. CONCLUSION: Healthy childhood eating patterns characterized by higher intakes of a variety of fruits, vegetables, whole grains, dairy, lean meat, poultry and fish are important modifiable predictors of lipid levels in late adolescence.

HCP-1, a protein involved in chromosome segregation, is localized to the centromere of mitotic chromosomes in Caenorhabditis elegans.

To learn more about holocentric chromosome structure and function, we generated a monoclonal antibody (mAb), 6C4, that recognizes the poleward face of mitotic chromosomes in Caenorhabditis elegans. Early in mitosis, mAb 6C4 stains dots throughout the nucleoplasm. Later in prophase, mAb 6C4 stains structures on opposing faces of chromosomes which orient towards the centrosomes at metaphase. Colocalization with an antibody against a centromeric histone H3-like protein and the MPM-2 antibody, which identifies a kinetochore-associated phosphoepitope present in a variety of organisms, shows that the mAb 6C4 staining is present adjacent to the centromere. Expression screening using mAb 6C4 identified a protein in C. elegans that we named HCP-1 (for holocentric protein 1). We also identified a second protein from the C. elegans genome sequence database, HCP-2, that is 54% similar to HCP-1. When expression of HCP-1 is reduced by RNA interference (RNAi), staining with mAb 6C4 is eliminated, indicating that hcp-1 encodes the major mAb 6C4 antigen. RNAi with hcp-1 and hcp-2 together results in aberrant anaphases and embryonic arrest at approximately 100 cells with different amounts of DNA in individual nuclei. These results suggest that HCP-1 is a centromere-associated protein that is involved in the fidelity of chromosome segregation.

HCP-4, a CENP-C-like protein in Caenorhabditis elegans, is required for resolution of sister centromeres.

The centromere plays a critical role in the segregation of chromosomes during mitosis. In mammals, sister centromeres are resolved from one another in the G2 phase of the cell cycle. During prophase, chromosomes condense with sister centromeres oriented in a back to back configuration enabling only one chromatid to be captured by each half spindle. To study this process, we identified a centromere protein (CENP)-C-like protein, holocentric protein (HCP)-4, in Caenorhabditis elegans based on sequence identity, loss of function phenotype, and centromeric localization. HCP-4 is found in the cytoplasm during interphase, but is nuclear localized in mitosis, where it localizes specifically to the centromere. The localization of HCP-4 to the centromere is dependent on the centromeric histone HCP-3; in addition, HCP-3 and HCP-4 are both required for localization of a CENP-F-like protein, HCP-1, indicating an ordered assembly pathway. Loss of HCP-4 expression by RNA-mediated interference resulted in a failure to generate resolution of sister centromeres on chromosomes, suggesting that HCP-4 is required for sister centromere resolution. These chromosomes also failed to form a functional kinetochore. Thus, the CENP-C-like protein HCP-4 is essential for both resolution sister centromeres and attachment to the mitotic spindle.

Increased collagen-linked pentosidine levels and advanced glycosylation end products in early diabetic nephropathy.

RATIONALE: Advanced glycosylation end products (AGEs) may play an important role in the development of diabetic vascular sequelae. An AGE cross-link, pentosidine, is a sensitive and specific marker for tissue levels of AGEs. OBJECTIVES: To evaluate the role of AGEs in the development of diabetic nephropathy and retinopathy, we studied pentosidine levels and the clinical characteristics of 48 subjects with insulin-dependent diabetes mellitus. Diabetic nephropathy was classified as normal, microalbuminuria, or gross proteinuria, and retinopathy was graded as none, background, or proliferative. NEWLY OBSERVED FINDINGS: Significant elevation of pentosidine (P = 0.025) was found in subjects with microalbuminuria or gross proteinuria (73.03 +/- 9.47 vs 76.46 +/- 6.37 pmol/mg col) when compared with normal (56.96 +/- 3.26 pmol/mg col). Multivariate analysis to correct for age, duration of diabetes, and gender did not modify the results. Elevated pentosidine levels were also found in those with proliferative when compared with those with background retinopathy (75.86 +/- 5.66 vs 60.42 +/- 5.98 pmol/mg col) (P < 0.05). CONCLUSIONS: Microalbuminuria is associated with elevated levels of pentosidine similar to those found in overt diabetic nephropathy suggesting that elevated AGE levels are already present during the earliest detectable phase of diabetic nephropathy.

Development of a Novel Six-Month Nutrition Intervention for a Randomized Trial in Older Men with Mobility Limitations.

OBJECTIVES: Nutrition impacts the development of sarcopenia and protein intake is an important modulator of skeletal muscle mass loss in older people. The Optimizing Protein Intake in Older Men with Mobility Limitation (OPTIMEN) Trial was designed to assess the independent and combined effects of higher protein intake and a promyogenic agent, testosterone, on lean body mass, muscle strength and physical function in older men with mobility disability. The purpose of this paper is to describe the experimental design and nutrition intervention, including techniques used by research dietitians to develop and deliver energy and protein-specific meals to the homes of community-dwelling participants. Strategies to enhance long-term dietary compliance are detailed. DESIGN: Randomized, double-blind, placebo-controlled six-month intervention trial. SETTING: Participants were recruited from Boston MA USA and surrounding communities. PARTICIPANTS: Older men who were mobility-limited (Short Physical Performance Battery (SPPB) 3-10) and consuming less protein (<0.83 g/kg/day) were recruited for this study. INTERVENTION: Here we report the successful implementation of a double-blind, placebo-controlled, parallel group, randomized controlled trial with a 6-month intervention period among community-living men, age 65 years and older with a mobility limitation. A controlled feeding plan was used to deliver required energy intakes and prescribed protein quantities of 0.8 or 1.3 grams/kilogram/day (g/kg/d) in three meals plus snacks and supplements. A 2x2 factorial design was used to assess the effects of protein level alone and in combination with testosterone (vs. placebo) on changes in lean body mass (primary outcome), muscle strength, and physical function. RESULTS: A total of 154 men met the eligibility criteria; 112 completed a 2-week run-in period designed to evaluate compliance with the nutrition intervention. Of these, 92 subjects met compliance eligibility criteria and agreed to be randomized; 85% completed the full trial. The study successfully delivered three meals per day to subjects, with a high degree of compliance and subject satisfaction. Overall self-reported compliance rates were 80% and 93% for the meals and supplements, respectively. Details of compliance strategies are discussed. CONCLUSION: This community-based study design may serve as a model for longer-term nutritional interventions requiring monitoring of dietary compliance in a home-based feeding and supplementation trial.

Formation of immunochemical advanced glycosylation end products precedes and correlates with early manifestations of renal and retinal disease in diabetes.

Elevated levels of advanced glycosylation end products (AGEs) have been found in multiple tissues in association with diabetic vascular complications and during the microalbuminuric phase of diabetic nephropathy. In this study, we have used an AGE-specific enzyme-linked immunosorbent assay (ELISA) to measure skin AGEs to determine whether elevated levels can be detected before the onset of overt microangiopathy. Subjects with type I diabetes (n = 48) were graded for the degree of nephropathy (normal [23], microalbuminuria [12], or macroalbuminuria [12]) and retinopathy (none [13], background [20], or proliferative [15]). Subgroups with a premicroalbuminuric phase of albumin excretion (< or = 28 mg/24 h, n = 27) or with the earliest stages of retinopathy (n = 27) were identified. A significant increase in tissue AGEs was found as urinary albumin increased during the premicroalbuminuric phase of nephropathy even when the data were adjusted for age and duration of diabetes (P = 0.005). Immunoreactive AGEs also increased as normal renal status advanced to microalbuminuria and macroalbuminuria (P = 0.0001 across groups). Significant elevation of AGEs was also found in association with the earliest stages of clinically evident retinopathy (early background versus minimal grades). In addition, higher AGE levels were found in subjects with proliferative retinopathy when compared with those with less severe retinopathy (P < 0.004 across groups). In contrast, no significant differences were found in tissue AGE levels between groups with or without early retinopathy based on pentosidine or fluorescent AGE measurements, although fluorescent AGEs correlated with albumin excretion.(ABSTRACT TRUNCATED AT 250 WORDS)

Relationship between glycemic control and collagen-linked advanced glycosylation end products in type I diabetes.

OBJECTIVE: To evaluate the relationship between glycemic control over a 3-yr period and tissue levels of advanced glycosylation end products. The development of renal failure, blindness, and generalized vascular occlusion continue to be the most serious ravages of diabetes. Tissue glycosylation and AGEs are felt to play an important role in the development of these sequelae, but no data are available on the relationship between AGEs and long-term glycemic control. RESEARCH DESIGN AND METHODS: We studied 48 subjects with type I diabetes. Glycemic control was determined by mean levels of HbA1, and AGEs were determined on collagenase digests of skin collagen by fluorescence at excitation/emission readings of 335/385 and 370/440 nm. RESULTS: To evaluate the relationship between glycemic control and AGE levels, control was classified as good (< or = 8.5%), fair (> 8.5% but < or = 10%), or poor (> 10%) on the basis of mean HbA1 levels during 1- and 3-yr periods. Analysis of the mean AGE levels for each level of glycemic control over 1-3 yr showed that AGEs differed significantly across categories of glycemic control (P = 0.04 and 0.003), with the lowest AGE levels associated with good and the highest with poor glycemic control. The relationship also was highly significant when adjusted for age, sex, and duration of diabetes, and when examined by Pearson's correlation coefficients (P = 0.02 and 0.008). CONCLUSIONS: Finding a relationship between glycemic control over 1-3 yr and tissue levels of AGEs suggests that AGEs can be modified and possibly reversed by improved glucose levels.

Parent-child relationships in nutrient intake: the Framingham Children's Study.

Nutrient intake affects many of the identified risk factors for coronary heart disease (CHD). Although CHD risk factors have been shown to aggregate within families, less is known about the familial aggregation of nutrient intake. We analyzed diet records for an average of 9 d per subject on 87 mothers, 83 fathers, and 91 children aged 3-5 y. A statistically significant but modest correlation (r less than 0.50) was found between parents' and children's intakes for most nutrients. The intake of nutrients was more strongly related between mothers and children than between fathers and children, and there was a stronger association with children's values for parents consuming more meals at home. The results of this study confirm that parents' eating habits have an impact on the nutrient intake of their preschool children; the study furnishes indirect support for dietary-intervention programs targeting families for the primary prevention of CHD.

Stage-specific expression of the Leishmania mexicana paraflagellar rod protein PFR-2.

A screen for Leishmania mexicana genes encoding promastigote-specific flagellar proteins resulted in isolation of genes encoding the major components of the paraflagellar rod. One of these, PFR-2, was characterized extensively. PFR-2 genes are present in the genome as a tandem array of three genes designated PFR-2A, PFR-2B, PFR-2C. PFR-2A and PFR-2B are encoded by a 3.1 transcript while PFR-2C is encoded by a 3.8-kb transcript that has a 3' UTR different from that of the 3.1-kb transcript. Both of these mRNAs were 15-fold more abundant in promastigotes than in amastigotes. Two transcripts immediately upstream of the locus were constitutively expressed while two downstream transcripts were fourfold more abundant in promastigotes than in amastigotes. The PFR genes will provide a good model system for analysis of stage-specific gene regulation in Leishmania as well as assist in the characterization of the function and organization of the paraflagellar rod.

Effects of bilateral injection of GABA into the substantia nigra on spontaneous behavior and measures of analgesia.

Bilateral injection of gamma-aminobutyric acid (GABA, 10-300 micrograms) into the substantia nigra (pars reticulata) of rats produced stereotyped sniffing and had an analgesic-like effect on the hot-plate but not on the tail-flick test. These effects of GABA (30 micrograms) were suppressed by simultaneous administration of a sub-convulsant dose of bicuculline methiodide (100 ng). Significant increases in locomotion occurred when GABA (300 micrograms) was injected along with the inhibitor of GABA-transaminase, d,l-gamma-vinyl-GABA (GVG; 5 micrograms) and the inhibitor of the uptake of GABA, 1-2,4-diaminobutyric acid (DABA; 5 micrograms). No other behavioral effects were observed following injection of GABA into the nigra, either alone or in combination with GVG and DABA. Bilateral injection of bicuculline (100-600 ng) into the nigra had strong convulsant actions. When injected simultaneously with bicuculline, GABA reduced bicuculline-induced seizures. These results are discussed in terms of their relevance to understanding the mechanisms that underlie the behavioral effects produced by injection of muscimol into the nigra.

Factors encouraging cohort maintenance in a longitudinal study.

Maintenance of the cohort is one of the primary challenges of a longitudinal study. At the end of 3 years of follow up in the Framingham Children's Study, a longitudinal study of young children and their parents, 100 of the original 106 families (94.3%) have remained in the study. A questionnaire was administered to identify factors contributing to the high rate of follow up to this point in the study. The attitudes of the staff, feedback to the subjects, the staff's handling of questions and problems, and association with the Framingham Heart Study emerged as the most important factors influencing continued participation in the study. In addition, 99% of the subjects stated that they believed the medical research to be important. We conclude that the quality of the communication with study participants and the subjects' perceived importance of the research have been the key factors in maintaining the cohort in this longitudinal epidemiologic study.

Bromocriptine-associated headache: possible life-threatening sympathomimetic interaction.

We present two cases of severe headache associated with the use of bromocriptine for lactation suppression in otherwise healthy women. In each case, the additional use of a therapeutic sympathomimetic agent resulted in extreme worsening of symptoms with development of hypertension and life-threatening complications (ventricular tachycardia and cardiac dysfunction in one case, seizures and cerebral vasospasm in the other). Sympathomimetics in combination with bromocriptine in patients with a bromocriptine-associated headache during the puerperium may be dangerous.

Epidemiologic studies among Amerindian populations of Amazonia. III. Intestinal parasitoses in newly contacted and acculturating villages.

The prevalences of intestinal parasites among the residents of three South American Indian villages in the process of acculturation were compared with those found in earlier unpublished surveys in two newly contracted village.s Although one individual in an acculturating village harbored 11 different intestinal parasites, in general the average number of different parasitic species carried per person was somewhat higher in the newly contacted villages. Helminth egg counts, performed on direct smears of each specimen from one newly contacted village, were low. There were no sex-associated differences in prevalences. The overall prevalences, unadjusted for age, were among the highest recorded for Amerindians. No Taenia species were present. Balantidium coli was present in two acculturating villages, concomitant with the beginning of agricultural practices which include raising swine. No cases of moderate or severe protein-calorie malnutrition was observed in any of the villages during the surveys. These limited data provide a baseline for future comparisons and, perhaps, a glimpse into the past.

Bilateral intranigral microinjection of morphine and opioid peptides produces antinociception in rats.

Bilateral intranigral microinjection of morphine produced dose-related and naloxone-reversible antinociceptive effects on the tail-flick and hot-plate tests. Intranigral injection of enkephalin had antinociceptive effects on both tests, and dynorphin had an antinociceptive effect on the hot-plate test. This is the first report of evidence that nigral opiate receptors may mediate antinociception.

A comparative study of one-year weight gain among users of medroxyprogesterone acetate, levonorgestrel implants, and oral contraceptives.

With the recent introduction and growing popularity of Depo-Provera Contraceptive Injection, concern about the potential for weight gain during treatment has been raised. The purpose of the present study was to determine whether or not Depo-Provera Contraceptive Injection is associated with greater weight gain, and incidence thereof, than Norplant implants or oral contraceptives. A retrospective chart review of patients seen at a state- and federally-funded clinic was conducted. Fifty women in each treatment group who met the study criteria were identified and included in the study evaluation. Mean one-year weight gain for subjects in each group was as follows: -2.0 pounds in the oral contraceptive group, -1.8 pounds in the Norplant implants group, and +0.1 pounds in the Depo-Provera Contraceptive Injection group. While results among treatment groups differed slightly, no significant weight change occurred in any of the treatment groups.

PIP: A retrospective analysis of charts of patients attending the Casa Grande Valley Center for Women in Casa Grande, Arizona, was conducted to compare weight gain over a 12 month period of users of Depo-Provera injectables containing medroxyprogesterone acetate with that of users of Norplant implants containing levonorgestrel and with that of oral contraceptive (OC) users. At the beginning of therapy, Depo-Provera users weighed less than users of Norplant and of OCs (61.7 vs. 65.1 and 64.5 kg, respectively; p 0.05). OC users tended to be older and have fewer children than the other groups (24 vs. 20.85 years and 1.5 vs. 2.2 children, respectively; p 0.05). After 12 months of treatment, Depo-Provera users experienced more weight gain than did the other groups (+0.06 vs. -0.93 for OC users and -0.81 for Norplant users; p = 0.045). Yet, the positive weight gain for Depo-Provera users as well as the weight loss for the other users were not statistically different from zero. Limitations of the study included no prospective design, nonrandomized subjects, nonblinded researchers, and lack of data on contraceptive discontinuations. Even though the findings suggest that Depo-Provera users are unlikely to gain weight, a larger, randomized, prospective study aiming to compare changes in weight with these contraceptives as well as nonhormonal contraceptive methods and to compare discontinuation rates due to side effects of each method is needed.

An investigation of the role played by the superior colliculus and ventromedial thalamus in self-injurious behavior produced by intranigral microinjection of muscimol.

Bilateral injection of muscimol (30 or 60 ng) into the substantia nigra (pars reticulata) of rats produced a variety of stereotyped acts, self-injurious behavior (SIB), and antinociception. Bilateral electrolytic lesions of the superior colliculus strongly suppressed SIB without reducing the antinociceptive effects of intranigral muscimol. Electrolytic lesions of the ventromedial thalamus had no effect on behavioral responses to intranigral muscimol. These studies suggest that the SIB produced by intranigral muscimol is mediated by neuronal pathways that terminate in or pass through the superior colliculus. The ventromedial thalamus does not appear to play a role in mediating behavioral responses to intranigral muscimol.

The feasibility of using rural health workers to determine cause of death in remote regions of Cameroon, West Africa.

The validity of the recent Global Burden of Disease Study (GBDS) was compromised by the lack of adult mortality data in developing countries, particularly in Sub-Saharan Africa. Verbal autopsies, in which health workers (HW), using questionnaires and algorithms, interview surviving family members to determine the cause of death, have proven useful in establishing priorities for the allocation of limited health care resources. Most reports, however, have come from large population centers. The feasibility of using health workers trained in verbal autopsy methodology to operate in remote rural areas of Africa has had limited testing. The records of 40 villagers who died in a Mission Hospital of the Northwest Province of Cameroon were reviewed, and the hospital discharge diagnosis, made by the attending physician, compared with that obtained by HW who administered a verbal autopsy to the family. In 70% of the cases the physician and HW were in exact agreement. Such a method, if confirmed in other studies among rural populations, may be an important approach to determining cause of death in many developing countries.