Longitudinal Study of Caries Development from Childhood to Adolescence.

The World Health Organization (WHO) stated that globally, dental caries is the most important oral condition. To develop effective prevention strategies requires an understanding of how this condition develops and progresses over time, but there are few longitudinal studies of caries onset and progression in children. The aim of the study was to establish the pattern of caries development from childhood into adolescence and to explore the role of potential risk factors (age, sex, ethnicity, and social deprivation). Of particular interest was the disease trajectory of dentinal caries in the permanent teeth in groups defined by the presence or absence of dentinal caries in the primary teeth. Intraoral examinations to assess oral health were performed at 4 time points by trained and calibrated dentist examiners using a standardized, national diagnostic protocol. Clinical data were available from 6,651 children. Mean caries prevalence (% D3MFT > 0) was 16.7% at the first clinical examination (ages 7-9 y), increasing to 31.0%, 42.2%, and 45.7% at subsequent examinations. A population-averaged model (generalized estimating equations) was used to model the longitudinal data. Estimated mean values indicated a rising D3MFT count as pupils aged (consistent with new teeth emerging), which was significantly higher (4.49 times; 95% confidence interval, 3.90-5.16) in those pupils with caries in their primary dentition than in those without. This study is one of the few large longitudinal studies to report the development of dental caries from childhood into adolescence. Children who developed caries in their primary dentition had a very different caries trajectory in their permanent dentition compared to their caries-free contemporaries. In light of these results, caries-free and caries-active children should be considered as 2 separate populations, suggesting different prevention strategies are required to address their different risk profiles.

A cluster-randomized controlled trial: fluoride varnish in school children.

We conducted a school-based parallel cluster randomized controlled trial with 36-month follow-up of children aged 7 to 8 years. Primary schools were randomly assigned to 2 groups: 3 applications of fluoride varnish (22,600 ppm) each year or no intervention. The primary outcome was DFS increment in the first permanent molars, with the hypothesis that 9 applications of varnish over 3 years would result in a lower increment in the test group. Follow-up measurements were recorded by examiners blind to the allocation. Ninety-five schools were randomized to the test and 95 to the reference groups; 1473 (test) and 1494 (reference) children participated in the trial. An intention-to-treat analysis was carried out with random effects models. The DFS increment was 0.65 (SD 2.15) in the test and 0.67 (SD 2.10) in the reference groups, respectively. There was no statistically significant difference between the groups. We were unable to demonstrate an effect for fluoride varnish when it was used as a public health intervention to prevent caries in the first permanent molar teeth (Inter-national Standard Randomized Controlled Trial Registration: ISRCTN: #72589426).

A randomised control trial of oral health education provided by a health visitor to parents of pre-school children.

OBJECTIVES: To determine the effect of oral health education carried out by a specially trained health visitor on the dental health of young children. DESIGN AND SETTING: Children, who were recruited during their 8-month distraction-hearing test, were randomly allocated to intervention and control groups. A home visit by the health visitor was arranged to parents in the intervention group who were given dental health advice. A second home visit, when the child was about 20 months old, focused on a completed diet record sheet and discussions about what and when the child was eating and drinking. Children in the intervention group received a toothbrush and toothpaste containing 440 ppm fluoride at both visits while those in the control group received the level of care usually provided by health visitors in the area. The children's teeth were examined when they were three years old and two years later as part of a census survey of 5-year-old children in the area. MAIN OUTCOME MEASURES: The numbers of decayed, missing and filled tooth surfaces. RESULTS: 251 children were recruited to the control group and 250 to the intervention group. At age three, they were examined; the mean dmfs scores were 2.19 (95% Confidence Interval: 1.41-2.97) in the control group (n = 171) and 2.03 (CI: 1.39-2.67) in the intervention group (n = 181). During the census survey 276 of the children in the study were examined at school. At this age the mean dmfs scores were 4.84 (CI: 3.39-6.29) in the control group (n = 129) and 3.99 (CI: 2.54-5.04) in the intervention group (n = 147). However, the mean dmfs of the remaining 2,253 children who were examined was 5.94 (CI: 5.55-6.33). CONCLUSIONS: No statistically significant differences in mean dmfs scores were found between the control and intervention groups of children, although, as the children grew older, the gap between them widened. However, the mean dmfs score of other 5-year-olds in the area was significantly worse than that of children in the intervention group. Asking the control parents to take part in the study and examining their children at three years may have had an effect on their dental health status and have made it more difficult to detect any differences achieved by the programme.

Vocal clans in sperm whales (Physeter macrocephalus).

Cultural transmission may be a significant source of variation in the behaviour of whales and dolphins, especially as regards their vocal signals. We studied variation in the vocal output of 'codas' by sperm whale social groups. Codas are patterns of clicks used by female sperm whales in social circumstances. The coda repertoires of all known social units (n = 18, each consisting of about 11 females and immatures with long-term relationships) and 61 out of 64 groups (about two social units moving together for periods of days) that were recorded in the South Pacific and Caribbean between 1985 and 2000 can be reliably allocated into six acoustic 'clans', five in the Pacific and one in the Caribbean. Clans have ranges that span thousands of kilometres, are sympatric, contain many thousands of whales and most probably result from cultural transmission of vocal patterns. Units seem to form groups preferentially with other units of their own clan. We suggest that this is a rare example of sympatric cultural variation on an oceanic scale. Culture may thus be a more important determinant of sperm whale population structure than genes or geography, a finding that has major implications for our understanding of the species' behavioural and population biology.

Culture in whales and dolphins.

Studies of animal culture have not normally included a consideration of cetaceans. However, with several long-term field studies now maturing, this situation should change. Animal culture is generally studied by either investigating transmission mechanisms experimentally, or observing patterns of behavioural variation in wild populations that cannot be explained by either genetic or environmental factors. Taking this second, ethnographic, approach, there is good evidence for cultural transmission in several cetacean species. However, only the bottlenose dolphin (Tursiops) has been shown experimentally to possess sophisticated social learning abilities, including vocal and motor imitation; other species have not been studied. There is observational evidence for imitation and teaching in killer whales. For cetaceans and other large, wide-ranging animals, excessive reliance on experimental data for evidence of culture is not productive; we favour the ethnographic approach. The complex and stable vocal and behavioural cultures of sympatric groups of killer whales (Orcinus orca) appear to have no parallel outside humans, and represent an independent evolution of cultural faculties. The wide movements of cetaceans, the greater variability of the marine environment over large temporal scales relative to that on land, and the stable matrilineal social groups of some species are potentially important factors in the evolution of cetacean culture. There have been suggestions of gene-culture coevolution in cetaceans, and culture may be implicated in some unusual behavioural and life-history traits of whales and dolphins. We hope to stimulate discussion and research on culture in these animals.

Comparison of effects of captopril used either alone or in combination with a thiazide diuretic on insulin action in hypertensive Type 2 diabetic patients: a double-blind crossover study.

AIMS: It has been suggested that the adverse metabolic effects of antihypertensive therapy offset some of the benefits of blood pressure reduction. It has also been suggested that angiotensin converting enzyme (ACE) inhibitors reduce insulin resistance and that, if used together with thiazide diuretics, the adverse effects of thiazides on insulin sensitivity may be eliminated. We examined the effects on insulin sensitivity of captopril either alone or in combination with bendrofluazide in 11 hypertensive Type 2 diabetic patients. METHODS: Insulin action was assessed using an isoglycaemic hyperinsulinaemic clamp in a double-blind, randomized, crossover study after a 6-week placebo run-in and following two 12-week treatment periods with captopril (C) (100 mg) alone or in combination with bendrofluazide (CB) (2.5 mg). RESULTS: Blood pressure was lower following CB compared to C (128/82 vs. 144/ 88 mmHg; P<0.005) and both were lower than baseline (162/101 mmHg; P < 0.001). CB resulted in a significant increase in fasting plasma glucose compared to C (9.7+/-0.8 vs. 8.5+/-0.6 mmol/; P < 0.05). Exogenous glucose infusion rates required to maintain isoglycaemia during hyperinsulinaemia were lower after CB compared to C (22.3+/-2.4 vs. 27.4+/-4.2 mol x kg(-1) x min(-1); P < 0.05). Suppression of endogenous glucose production was reduced after CB compared to baseline (4.0+/-0.6 vs. 2.4+/-0.5 mol x kg(-1) x min(-1); P< 0.05). CONCLUSIONS: Combination of bendrofluazide with captopril lowered blood pressure but resulted in deleterious effects on insulin action compared to captopril alone.

Cultural selection and genetic diversity in matrilineal whales.

Low diversities of mitochondrial DNA (mtDNA) have recently been found in four species of matrilineal whale. No satisfactory explanation for this apparent anomaly has been previously suggested. Culture seems to be an important part of the lives of matrilineal whales. The selection of matrilineally transmitted cultural traits, upon which neutral mtDNA alleles "hitchhike," has the potential to strongly reduce genetic variation. Thus, in contrast to other nonhuman mammals, culture may be an important evolutionary force for the matrilineal whales.

Social evolution in toothed whales.

Two contrasting results emerge from comparisons of the social systems of several odontocetes with terrestrial mammals. Researchers have identified remarkable convergence in prominent features of the social systems of odontocetes such as the sperm whale and bottlenose dolphin with a few well-known terrestrial mammals such as the elephant and chimpanzee. In contrast, studies on killer whales and Baird's beaked whale reveal novel social solutions to aquatic living. The combination of convergent and novel features in odontocete social systems promise a more general understanding of the ecological determinants of social systems in both terrestrial and aquatic habitats, as well as the relationship between relative brain size and social evolution.

The presentation of newly-diagnosed diabetic patients in Uganda.

We assessed the clinical characteristics of newly-diagnosed diabetic patients presenting to the Mulago Hospital Diabetic Clinic for the first time between 1 January 1993 and 10 August 1994. There were 252 patients: 117 men and 135 women. Mean age at onset of diabetes was 45 years (range 2-87 years) and peak incidence was at 40-49 years. Body mass index (BMI) was available in only 71 patients, of whom 53.5% (33.8% female, 19.7% male) were overweight (BMI > 25 in women, in > 27 men) and 11.3% (8.5% men, 2.8% women) were underweight (BMI < 20). Obesity was more marked in young women. Almost all patients presented with the classical symptoms of diabetes, and the majority were severely hyperglycaemic. A family history of diabetes was identified in 16%. Concurrent illnesses at diagnosis of diabetes were unusual. Sepsis was commonest (11.9%), followed by malaria (7.8%), tuberculosis (1.2%), AIDS (1.2%) and pancreatitis (0.8%). Peripheral neuropathy was present in 46.4% of patients, hypertension (BP > 150/100) in 27.3%, impotence in 22.2% of the men, proteinuria in 17.1%, ischaemic heart disease in 4.8%, foot ulcers in 4.0% and cataracts in 3.2%. Insulin was the most commonly prescribed treatment (52.8%); 31% of patients received oral hypoglycaemic agents, only 15.1% were managed on diet only, and 1.2% opted for herbal medicine.

Patterns of kinship in groups of free-living sperm whales (Physeter macrocephalus) revealed by multiple molecular genetic analyses.

Mature female sperm whales (Physeter macrocephalus) live in socially cohesive groups of 10-30, which include immature animals of both sexes, and within which there is communal care of the young. We examined kinship in such groups using analyses of microsatellite DNA, mitochondrial DNA sequence, and sex-linked markers on samples of sloughed skin collected noninvasively from animals in three groups off the coast of Ecuador. Social groups were defined through photographic identification of individuals. Each group contained about 26 members, mostly female (79%). Relatedness was greater within groups, as compared to between groups. Particular mitochondrial haplotypes were characteristic of groups, but all groups contained more than one haplotype. The data are generally consistent with each group being comprised of several matrillines from which males disperse at about the age of 6 years. There are indications of paternal relatedness among grouped individuals with different mitochondrial haplotypes, suggesting long-term associations between different matrilines.

Blood pressure responses to phenylephrine infusions in subjects with Cushing's syndrome.

The pathogenesis of the hypertension associated with Cushing's syndrome is not completely understood. Sensitivity to pressor agents may play a role. We have investigated this possibility by measuring blood pressure (BP) during incrementally increasing infusions of the alpha-adrenergic agonist phenylephrine. Ten subjects (8 women: 2 men), aged 40 +/- 5 years (mean +/- s.e.m.) with Cushing's syndrome were studied. All had raised BP but none had received any anti-hypertensive treatment for at least 16 days before study. Ten age- (40 +/- 5 years) and sex-matched control subjects were also studied. At 13.30, 30 min after a light meal, subjects had an intravenous cannula inserted, ECG leads and a sphygomanometer cuff attached, and then rested supine in a quiet room for 30 min. Phenylephrine was then infused incrementally at intervals of 5 min. The doses used were 0.3, 0.6, 0.9, 1.35 and 2 micrograms/kg/min. Basal mean blood pressure (MAP) was 108 +/- 2 mm Hg (mean +/- s.e.m.) in patients and 74 +/- 3 mm Hg in controls (P < 0.05) and pulse rate was 75 +/- 5 and 68 +/- 3 beats/min (NS), respectively). MAP increased and pulse rate decreased linearly with time. The rate of rise of MAP was 1.7 +/- 0.4 mm Hg/min in subjects and 1.1 +/- 0.2 mm Hg/min in controls (NS). The rate of decrease of pulse was significantly more rapid in Cushing's subjects than in controls (1.4 +/- 0.2; 0.6 +/- 0.1 beats/min2; P < 0.05). The lack of any increased BP response to alpha-adrenergic stimulation suggests that altered sensitivity is not a major cause of the increased BP seen in patients with Cushing's syndrome.

Growth hormone treatment of adults with growth hormone deficiency: results of a 13-month placebo controlled cross-over study.

OBJECTIVE: We aimed to study the effect of biosynthetic growth hormone (GH) replacement in growth hormone deficient adults. DESIGN: We performed a double-blind placebo-controlled cross-over study of 6 months biosynthetic GH, replacement and 6 months placebo separated by a 1-month's washout period. PATIENTS: Fourteen growth hormone deficient adults were studied. MEASUREMENTS: We measured total body weight, percentage fat mass, lean body mass, muscle volume, exercise capacity, maximum oxygen consumption, muscle strength, bone mineral content, a number of biochemical parameters, IGF-I, GH antibodies and psychological well-being. RESULTS: Total body weight remained unchanged, but lean body mass increased (before GH mean +/- SEM 49.8 +/- 5.5, after 53.4 +/- 5.6 kg; placebo before 51.2 +/- 5.4, after 50.4 +/- 5.1 kg; P less than 0.05 and fat mass decreased (before GH 21.5 +/- 4.1, after 19.3 +/- 4.3; placebo before 19.3 +/- 4.0, after 22.5 +/- 4.5 kg; P less than 0.05). Thigh muscle volume increased: (before GH 94.1 +/- 7.7, after 99.5 +/- 8.4 ml; placebo before 99.3 +/- 8.6, after 95.4 +/- 7.8 ml/0.8 mm computerized tomographic slice; P less than 0.05). Exercise capacity increased (before GH 174 +/- 15, after 199 +/- 18.9 watts; placebo before 162.5 +/- 2.3, after 154 +/- 19.8 watts; P less than 0.05), as did maximum oxygen consumption (before GH 1.93 +/- 0.2, after 2.17 +/- 0.2 l/m; placebo before 1.92 +/- 0.3, after 1.98 +/- 0.2 l/m; P less than 0.05). There was no change in quadriceps muscle strength. Alkaline phosphatase increased (before GH 87.5 (32-158), after 106.0 (49-179) U/I, placebo 99.5 (50-145), after 72.0 (40-111) U/I; P less than 0.05) without a change in the spinal bone density. IGF-I increased (before GH 62 (36-97), after 216 (62-362) micrograms/l; placebo before 59 (52-112), after 60.5 (38-94) micrograms/l; P less than 0.05). Carbohydrate tolerance remained unchanged as did fasting lipids, serum sodium, potassium, urea, calcium, phosphate and liver transaminases. Psychological well-being remained unchanged. No growth hormone antibodies were detected before or after GH treatment. CONCLUSIONS: GH alters the body composition of growth hormone deficient adults and leads to improved exercise capacity; alkaline phosphatase activity increases but without a change in spinal bone density, and carbohydrate tolerance remains unaltered.

Physiological growth hormone secretion in adult growth hormone deficiency: comparison with normal controls.

A comparison was made between the pulsatile pattern of growth hormone secretion in 14 growth hormone deficient adults (serum growth hormone less than 7 mU/I following insulin-stimulated hypoglycaemia) and 14 age and sex matched controls. The 24-h secretory profile was generated by 2-hourly sampling from 0800 to 2200 h, and 30-min sampling from 2200 to 0600 h. Plasma GH in each sample was measured using a double antibody radioimmunoassay. The profiles were analysed using a computer program (Pulsar). Sleep-electroencephalography was recorded in all subjects. The total amount of GH secreted in a 24-h period (area under the curve over baseline) was significantly less in the growth hormone deficient group (P less than 0.002). The pulse frequency, amplitude, height and percentage GH secreted in peaks were also significantly less in the growth hormone deficient group (P less than 0.002 respectively). We conclude that adults deficient in GH, as defined by conventional pharmacological stimuli, are in addition physiologically deficient of pulsatile GH secretion.