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The objective of this laboratory study was to assess the Sensodyne Mikro Aktiv extra soft toothbrush, compared with the Oral-B Indicator soft toothbrush, for interproximal access efficacy (IAE).Six toothbrushes of each product were tested four times, for a total of twenty-four tests on each toothbrush design. In the IAE assay, the tooth brushing technique involved independent evaluations of each toothbrush in a vertical or horizontal brushing motion, tooth shapes simulating anterior and posterior teeth, and a brushing weight of 250 g. The brushing apparatus was set to brush for 15 seconds at two strokes per second with a 50 mm stroke. All readings were measured with 3x magnification by a single investigator.The mean IAE value on anterior tooth shapes, with vertical and horizontal brushing, was significantly (p0.001) higher for the Sensodyne Mikro Aktiv toothbrush than for the Oral-B Indicator toothbrush. When the IAE values were combined to give an overall brushing average, the Sensodyne Mikro Aktiv toothbrush was significantly (p0.001) higher compared to the Oral-B Indicator toothbrush.The Sensodyne Mikro Aktiv toothbrush has demonstrated superiority to the Oral-B Indicator toothbrush for access into interproximal areas using this laboratory methodology.

Bi-level optimization algorithms have been developed for use in a variety of problems, including network design and defense systems and optimization under uncertainty, and network interdiction applications. These algorithms often employ a technique that divides the decision-making process into a first-stage master problem wherein one set of decisions are determined, after which a set of separable second-stage problems are based on the first-stage decisions. The master problem determines an optimistic assessment of the costs incurred in the second stage; this assessment is then refined by a set of linear functions called cutting planes, which provide cause-and-effect relationships between the first- and second-stage decisions. However, these cutting planes are often ineffective in practical problems. The improvement of these cutting planes is the subject of this proposal. The investigator encountered a surprising feature of some bi-level problems, in which an exponential number of cutting planes may need to be generated at each stage. By reformulating the first-stage problem using slightly more variables and constraints, it was possible to capture all of these cutting planes with a single inequality in the new variable space. Problems that were thought to be impossible to optimality are shown to in fact be solvable within reasonable computational limits.

The rate of movement of chromium (III) chloride through the gastrointestinal tract of rats was investigated. In the first experiment 85% of rats intubated with 51 CrCl 3 had more than 1% of the administered 51 Cr below the cecum after four hours. In the second study, most 51 Cr recovered in the small intestine reached the ileum one hour after initiation of feeding 2 g diet containing 51 CrCl 3 . In the third experiment, the intestine was ligated in situ; ligation blocked 51 Cr transit. 51 Chromium appeared to be associated with the fluid portion of the ingesta which may negate the use of CrCl 3 as a marker for rate of passage of dietary components.

Data are accumulating that support the hy- pothesis that inadequate zinc nutriture will result in an impair- ment of vitamin A utilization. Therefore, zinc and vitamin A status were assessed in 283 schoolchildren aged 7-1 3 y in Northeast Thailand. More than one-fourth had serum vitamin A concentrations < 0.86 �mol/L, with a mean (± SD) concen- tration of 1.06 ± 0.31 �cmol/L compared with 1.26 ± 0.02 zmol/L for US children of similar age. Seventy percent had low serum zinc concentrations, < 10.7 �mol/L. Twenty-three percent ofthe children exhibited both low serum zinc and vita- mm A concentrations. The mean concentration of retinol- binding protein (RBP)was bower for children in this study com- pared with healthy Thai children in Bangkok, 22.5 ± 6.6 vs 25.3 ± 6.0 mg/L, respectively. Serum zinc and RBP were sig- nificantly correlated (p < 0.001) whereas vitamin A and zinc were not correlated. These data suggest that a high proportion ofrural schoolchildren in Northeast Thailand are at risk of in- adequate zinc and/or vitamin A nutriture. Am J Clin Mar 1990;52:564-7.

In the 1950s, Puerto Rico began an active industrialization program. We used data from the 1982 Puerto Rico Fertility and Family Planning Assessment to describe the trend in the incidence of breastfeeding in Puerto Rico over time and to ascertain some of its determinants. From 1946 through 1982, 5,884 infants were born among this statistically representative sample of reproductive-aged women. The proportion of infants who had ever been breastfed was 59 percent for births before 1960 (mean duration = 7.8 months), dropped to 25 percent for infants born from 1970 to 1974 (mean duration = 4.9), and rose to 38 percent for births delivered from 1980 to 1982 (mean duration = 3.4). Prior breastfeeding experience was an important determinant of breastfeeding a newborn. Infants of mothers who had breastfed a previous baby were 7.3 times more likely to be breastfed (95% confidence interval = 6.6, 8.0) compared with infants of mothers who had not previously breastfed. The 38 percent of infants who were breastfed in Puerto Rico in the early 1980s is below the 74 percent to 97 percent reported in Latin America and below the 54 percent reported in the United States for the same period. This study provides baseline data for any future intervention strategies.

Alström syndrome (AS) is a rare autosomal recessive condition characterized by retinal degeneration, childhood obesity, and severe insulin resistance. Dilated cardiomyopathy of unknown aetiology is a well-recognized and potentially lethal complication. The aim of this study was to investigate the relationship between vascular function, hyperinsulinaemia and cardiac performance in AS.Fifteen subjects with AS (mean age 21 years, range 10-35) were studied and compared with age-, sex-, and blood pressure-matched healthy controls. Large artery stiffness and wave reflections were assessed in both groups by measuring aortic and brachial pulse wave velocity (PWV) (carotid-femoral and carotid-radial) and augmentation index (AIX) (Sphygmocor). In AS subjects, left ventricular function was assessed by echocardiography and metabolic parameters including fasting insulin, glucose, lipids and brain natriuretic peptide were also measured.Comparing AS subjects vs. controls (mean +/- SD), AIX was elevated in AS subjects (18 +/- 9% vs. 3 +/- 11%, P0.0001). No significant changes in brachial PWV (8.1 +/- 1.3 m s(-1) vs. 7.3 +/- 1.1 m s(-1), P = 0.14) or aortic PWV (6.5 +/- 1.1 m s(-1) vs. 6.0 +/- 1.0 m s(-1), P = 0.26) were observed. AS subjects were hyperinsulinaemic and had disturbances in lipid profiles relative to controls. No correlations were observed between vascular, metabolic and echocardiographic parameters.In AS there are alterations in the shape of the central arterial pressure waveform associated with augmented aortic systolic pressure and indicative of increased wave reflection. Unfavourable central arterial haemodynamics in AS may contribute to the development of cardiomyopathy but other aetiological factors are probably involved.

Background Anabolic androgenic steroids are used by some bodybuilders to enhance performance. While the cardiovascular implications of supraphysiological androgen levels requires further clarification, use is associated with sudden death, left ventricular hypertrophy, thrombo-embolism and cerebro-vascular events. Materials and methods To further understand the effect of androgenic anabolic steroid abuse on vascular function, this study assessed vascular stiffness (pulse-wave analysis) and cardiovascular risk factors in 28 male, bodybuilding subjects, of whom ten were actively receiving anabolic agents (group A; 26·4 ± 7·2 years) and eight had undergone a 3-month ‘wash-out’ period (group B; 32·1 ± 7·1 years). The remaining ten bodybuilding subjects (group C; 24·4 ± 4·4 years) denied any past use of anabolic steroids or other performance enhancing drugs. Comparisons were made with ten sedentary male controls (group D, 29·3 ± 4·7 years). Results Endothelial independent dilatation in response to glycerol trinitrate was significantly impaired in the group currently using anabolic steroids (group A) compared with the other three groups [A (5·63 ± 3·24%) versus; B (11·10 ± 4·91%), C (17·88 ± 9·2%) and D (14·46 ± 3·9%), P < 0·0005, respectively], whereas no significant differences in endothelial-dependant dilatation were detected between the groups [A (5·0 ± 3·0%), B (7·4 ± 3·4%), C (9·6 ± 4·5%) and D (8·2 ± 3·3%), P < 0·059, respectively]. Conclusions Previous studies described a decline in vascular reactivity occurring in bodybuilding subjects which is independent of anabolic steroid use and may result from smooth muscle hypertrophy with increased vascular stiffness. This study revealed impaired vascular reactivity associated with anabolic agents and that improvement in vascular function may occur following their discontinuation.

As the size and number of wind power plants (also called wind farms) increases, power system planners will need to study their impact on the power system in more detail. As the level of wind power penetration into the grid increases, the transmission system integration requirements becomes more critical. A very large wind power plant may contain hundreds of megawatt-size wind turbines. These turbines are interconnected by an intricate collector system. While the impact of individual turbines on the larger power system network is minimal, collectively, wind turbines can have a significant impact on the power systems during a severe disturbance such as a nearby fault. Since it is not practical to represent all individual wind turbines to conduct simulations, a simplified equivalent representation is required. This paper focuses on our effort to develop an equivalent representation of a wind power plant collector system for power system planning studies. The layout of the wind power plant, the size and type of conductors used, and the method of delivery (overhead or buried cables) all influence the performance of the collector system inside the wind power plant. Our effort to develop an equivalent representation of the collector system for wind power plants is an attempt to simplify power system modeling for future developments or planned expansions of wind power plants. Although we use a specific large wind power plant as a case study, the concept is applicable for any type of wind power plant.

The objective of this series of laboratory studies was to assess a new triple-head toothbrush, the DR BEST FreiKopf, compared to the Oral-B 40 toothbrush, for interproximal access efficacy (IAE), gingival margin cleaning (GMC), and subgingival access (SA) as measures of toothbrush efficacy.In each procedure, six toothbrushes of each product were tested four times for a total of twenty-four tests on each toothbrush design. In the IAE assay, the tooth brushing technique involved independent evaluations of each toothbrush in a vertical or horizontal brushing motion, tooth shapes simulating anterior and posterior teeth, and a brushing weight of 250 g. The brushing apparatus was set to brush 15 seconds at two strokes per second with a 50 mm stroke. In the GMC assay, the tooth brushing technique involved independent evaluations of each toothbrush in a horizontal brushing motion, tooth shapes simulating posterior teeth, and a brushing weight of 500 g. Simulated gingivae were prepared from self-curing dental acrylic. The brushing apparatus was set to brush for 60 seconds at two strokes per second with a 15 mm stroke. In the SA evaluations, the tooth shapes simulating posterior teeth were used, as well as a brushing weight of 500 g for 60 seconds at two strokes per second with a 15 mm stroke. All readings were measured with 3x magnification by one investigator.The mean IAE value on anterior and posterior tooth shapes, with vertical and horizontal brushing, and overall, was significantly (p0.001) higher for the triple-head toothbrush than for the Oral-B 40 toothbrush. In the GMC assay, the triple-head toothbrush had a significantly (p0.001) superior mean value compared to the Oral-B 40 product tested. In the SA study, the triple-head toothbrush was significantly (p0.001) superior compared to the Oral-B 40 toothbrush product tested.The triple-head toothbrush has demonstrated superiority to a traditional flat-head toothbrush for access into interproximal areas, and for removing deposits from the gingival margin, as well as below the gumline, in these laboratory assays.

We report a breast-fed infant with clinical evidence of rickets and with dilated cardiomyopathy who responded well to supplemental calcium and vitamin D. We believe that this is the first report of such an association in an American child.

Acromegaly is associated with increased cardiovascular risk. Although conventional risk factors such as glucose intolerance, hypertension, and dyslipidemia probably contribute, there may also be direct effects of GH/IGF-I excess on the vasculature. To study the effects of GH excess on the vasculature, we have assessed arterial stiffness in acromegalic subjects with and without active disease and have investigated the effects of Sandostatin LAR (OCT-LAR) on vascular function. Sixteen normotensive subjects with acromegaly (10 males and 6 females) and 8 healthy controls were studied. Of the acromegalic subjects, eight had active disease (group A), and eight were cured (GH2.5 mU/liter; group B). The three groups were age, sex, and blood pressure matched. Group A subjects were restudied after 3 and 6 months of OCT-LAR therapy. Arterial stiffness was assessed by analyzing central arterial pressure waveforms derived from measured radial artery waveforms. This allowed determination of the augmentation of central pressure and the augmentation index. Lipids, glucose, and IGF-I were also measured. Comparing the three groups (ANOVA; mean +/- SD), the augmentation index was higher in group A (28 +/- 12 vs. 12 +/- 13%; P0.01) but not in group B (22 +/- 7 vs. 12 +/- 13%; P = 0.60), compared with controls. IGF-I was higher in group A (50.3 +/- 21.2 nmol/liter; P0.01), compared with group B (22.5 +/- 8.9 nmol/liter) and controls (19.5 +/- 5.3 nmol/liter). On regression analysis, IGF-I concentration was identified as a strong independent predictor of the augmentation index (beta = 0.50; P = 0.007). There were no significant differences in aortic systolic pressure, aortic diastolic pressure, lipids, or glucose. Compared with baseline, OCT-LAR treatment resulted in a lowering of augmentation index at 3 months (20 +/- 15 vs. 28 +/- 12%; P0.05), but at 6 months (24 +/- 16%; P = 0.21) there was no significant change. IGF-I was reduced from 50.3 +/- 21.2 nmol/liter at baseline to 31.4 +/- 13.2 nmol/liter at 3 months (P0.05) and 26.6 +/- 15.8 nmol/liter at 6 months (P0.05). In conclusion, acromegaly is associated with changes in the central arterial pressure waveform, suggesting large artery stiffening. This may have important implications for cardiac morphology and performance in acromegaly as well as increasing the susceptibility to atheromatous disease. Large artery stiffness is reduced in cured acromegaly and partially reversed after pharmacological treatment of active disease.

Insulin therapy may influence cardiovascular disease (CVD) and lipid metabolism in type 2 diabetes (T2D). Exaggerated postprandial lipaemia (PPL) is a feature of diabetic dyslipidaemia affecting CVD via enhanced oxidative stress (OS) and endothelial dysfunction. We assessed endothelial function and OS during PPL following insulin and vitamin C. Twenty (17 M) T2D patients were studied (mean Hba1c 8.4%) at baseline, following 6 weeks of insulin lispro (0.2 Iu kg-1) and vitamin C 1-g daily. Eight-h lipid and glucose profiles were measured following a fatty meal. Endothelial function (flow-mediated vasodilatation: FMD) and OS were measured at fasting, 4 h and 8 h.Glucose, body mass index, and total and LDL cholesterol remained unchanged. FMD improved. Placebo group: fasting, 1.1 +/- 1.2 to 4.2 +/- 1.1% (P0.001); 4-h, 0.3 +/- 1.2 to 3.1 +/- 0.9% (P0.01); 8-h, 0.7 +/- 1.1 to 3.76 +/- 1.1% (P0.001). Vitamin C group: fasting, 0.9 +/- 1.1 to 6.1 +/- 1.3% (P0.001); 4-h, 0.7 +/- 1.5 to 4.9 +/- 2.1% (P0.001); 8-h, 0.8 +/- 0.9 to 5.8 +/- 0.6% (P0.01). Post-prandial lipaemia was attenuated: TG area-under-curve (mmol L-1 8 h-1), 52.6 +/- 11 to 39.1 +/- 12.5 (placebo group), P0.02; and 56.9 +/- 8 to 40.1 +/- 10.3 (vitamin C group), P0.02. Oxidative stress was reduced, with greater changes in the vitamin C group.Insulin may thus exert vascular benefits in T2D, by modifying fasting and postprandial lipid metabolism resulting in reduced OS and improved EF. Vitamin C therapy may augment the vascular benefits of insulin in T2D through additional effects on OS and EF.

Malnutrition is common in sick elderly people on admission to hospital and in the community. We conducted a randomised controlled trial to determine if nutritional supplementation after discharge from hospital improved nutritional status and functional outcomes, or reduced health-care costs.Elderly malnourished subjects were randomised to 8 weeks of supplementation or no supplementation post discharge, and followed up for 24 weeks. Weight, body mass index, anthropometrics, handgrip strength, quality of life and requirements for health-care professionals' services and social services were measured throughout the study.Nutritional status improved significantly from baseline to week 24 in the intervention group (P0.05), but not in the control group. There was no significant difference in nutritional status between groups at week 24. Handgrip strength improved significantly in the intervention group during supplementation, and was significantly different from that of the control group at week 8, but decreased thereafter. There was no significant difference in quality of life or health economic outcomes between groups at week 24.In already malnourished elderly subjects, it may be too late to expect to improve function or quality of life or to reduce health-care costs simply by providing nutritional supplements after hospitalisation. Prevention is key. All elderly patients should be nutritionally assessed as part of their routine care, and appropriate intervention initiated early.

Hypothyroidism is associated with cardiovascular dysfunction. It is increasingly apparent that stiffening of central arteries may lead to increased afterload and cardiac dysfunction. We noninvasively studied the peripheral and central pressure waveforms in 12 untreated hypothyroid patients as well as in 12 age-, sex-, and body mass index-matched controls using the technique of pulse wave analysis from recordings at the radial artery. Indexes of arterial stiffness, augmentation index (AI) and augmentation of central arterial pressure (AG), were derived as well as time of travel of the reflected wave (TR), a direct estimate of aortic pulse wave velocity. At baseline, there were no significant differences between the 2 groups in brachial and aortic blood pressures. Hypothyroid patients had significantly higher AI than controls (mean +/- SEM[SCAP], 32.0 +/- 3.4% vs. 17.0 +/- 2.4%; P0.0005) even when corrected for heart rate (AI(C); 28.0 +/- 3.2% vs. 17.0 +/- 2.4%; P0.006) and AG (13.0 +/- 2.2 vs. 7.0 +/- 2.1 mm Hg; P0.03) together with a lower TR (132.0 +/- 4.1 vs. 142.0 +/- 1.5 msec; P0.03). After 6 months of therapy with T(4), all patients were euthyroid. AI(C) had decreased in the patient group (23.0 +/- 3.2% vs. 28.0 +/- 3.2%; P0.01) as had AG (9.0 +/- 1.5 vs. 13.0 +/- 2.2 mm Hg; P0.008), but TR was significantly higher (142.0 +/- 3.0 vs. 132.0 +/- 4.1 msec; P0.008). AI correlated with age in all groups (hypothyroid group: r = 0.937; P0.0005; control group: r = 0.804; P0.0005), but correlated with TSH level only among controls (r = 0.591; P0.05). This study confirms that hypothyroidism is associated with increased cardiovascular risk, as evidenced by increased augmentation of central aortic pressures and central arterial stiffness. Furthermore, these abnormalities are reversed after adequate T(4) replacement.

One candidate for an endogenous mesoderm-inducing factor in Xenopus is derrière, a member of the TGFβ family closely related to Vg1. In this paper we first show that derrière is able to exert long-range effects in the early Xenopus embryo, reinforcing the view that it functions as a secreted factor required for proper formation of posterior structures. Analysis of the derrière promoter shows that expression of the gene is controlled through a complex inductive network involving VegT and TGFβ-related molecules and also, perhaps, FGF family members. The work confirms that derrière plays an important role in mesoderm formation and it illustrates the complex regulation to which inducing factors are subject.

Nine men (25.11 +/- 1.16 years) performed 3 different test sessions. In the control session, subjects performed a 10-second sprint cycle test and 1 repetition maximum (1RM) in the back squat. The 5-minute test session consisted of 10 x 1 repetition in the parallel back squat exercise at 90% of their 1RM, 5 minutes of rest, and then a 10-second sprint cycle test. The 20-minute test session consisted of the same test protocol as the 5-minute test session except that the subjects rested for 20-minutes prior to the sprint cycle test. Significant differences were found in average power and average power relative to body weight (F = 5.684, p = 0.014, and F = 1.258, p = 0.006, respectively) for the 5-minute test session. The authors conclude that this particular squat protocol could have a potential carry-over effect into improvements in 100-m sprint times when performing the squats 5-minutes prior to performance.

The mesoderm of the amphibian embryo is formed through an inductive interaction in which cells of the vegetal hemisphere of the embryo act on overlying equatorial cells. My laboratory is studying the Brachyury gene, which plays a key role in this interaction, being both necessary and sufficient for normal mesoderm formation. In this article I describe our attempts to understand how Xenopus Brachyury (Xbra) is activated in the right cells at the right time, and then to understand how Xbra exerts its effects.

Recall bias remains a concern in case-control studies, although few investigations have found evidence of differential recall. This study examined whether differences in occupational exposure reporting occur in volunteered vs. prompted questionnaire responses.In a large, population-based, case-control study of a childhood cancer, neuroblastoma, we calculated odds ratios for broad occupational exposure groups on the assumption that in the absence of recall bias, risk estimates for such broad groupings should be close to the null value.Prompted exposures and work activities showed little evidence of differential recall by parents of cases and controls (all OR1.2), but case parents were more likely to volunteer information about other exposures or activities (ORs: 1.35-1.71). Case mothers were also more likely than control mothers to report activities involving indirect exposure (OR = 1.41).These findings suggest that prompted exposure questions are less likely to be subject to recall bias than open-ended questions.

The purpose of the present work was to examine effects of the Cu-Fe interaction on intestinal beta-carotene 15,15'-dioxygenase activity when a wide range of dietary Fe (deficiency to excess) was used in relation to Cu status of rats. The effect of dietary carbohydrates was also examined since they play a role in the Cu-Fe interaction in vivo. Weanling male Sprague-Dawley rats (n 72) were divided into twelve dietary groups, which were fed on either low-, normal-, or high-Fe levels (0.9, 9.0, and 90.0 mmol Fe/kg diet respectively) combined with Cu-adequate or -deficient levels (0.94 and 0.09 mmol Cu/kg diet respectively) and with starch or fructose in the diets. The data showed that both Fe concentration and beta-carotene 15,15'-dioxygenase activity in small intestinal mucosa were enhanced with increasing dietary Fe and with Cu deficiency v. Cu adequacy. Dietary fructose did not aggravate the Fe-enhancement, related to Cu deficiency, in the small intestine; however, fructose increased the intestinal dioxygenase activity in rats fed on normal- or high-Fe diets when compared with starch controls. Thus, the highest intestinal dioxygenase activity associated with the lowest hepatic retinol (total) concentration was found in rats fed on the Cu-deficient, high-Fe, fructose-based diet. Finally, a positive linear relationship was found between the dioxygenase activity and Fe concentration in intestinal mucosa. In conclusion, the data indicate that beta-carotene 15,15'-dioxygenase activity requires Fe as cofactor in vivo and the enzyme is modulated by the three dietary components: Cu, Fe, and fructose.

To analyze the presentation, evaluation, and treatment of a subset of patients with well-differentiated thyroid carcinoma who present with a lateral neck mass and no palpable disease in the thyroid gland.A retrospective review of all patients undergoing thyroidectomy for malignancy.A database of all thyroidectomies performed for malignancy by the Vanderbilt University Department of Otolaryngology-Head and Neck Surgery from 1992 to 1997 was created. Patients who presented with an isolated neck mass without evidence of palpable disease in the thyroid were selected for the study population.There were 60 cases of thyroid malignancy, with 14 cases (23.3%) that presented as isolated lateral neck mass. The characteristics of this group (compared with the population of all thyroid malignancies) include younger age at presentation (37.7 +/- 15.2 y vs. 49.8 +/- 15.6 y; Student t test: P = .019) and long-standing presence of symptoms (27.4 +/- 39.6 mo vs. 3.6 +/- 3.9 mo; P = .023). These patients generally presented from a referring facility after having an excisional biopsy, which was 100% accurate. Fine-needle aspiration is becoming more useful and was 66.7% accurate. Histological examination revealed cancer in the thyroid gland in all patients, 11 cases of papillary carcinoma, 2 follicular carcinomas, and one medullary carcinoma The mean size of the primary focus was 10.9 +/- 8.7 mm, with 29% demonstrating bilateral disease and 14% demonstrating multifocal disease in the ipsilateral gland. The neck specimens revealed an average of 5.3 +/- 3.2 metastatic nodes in levels II-IV and 3.9 +/- 4.6 metastatic nodes in the paratracheal region.Based on this patient population, the long-standing lateral neck mass in the young patient should raise the physician's index of suspicion for thyroid carcinoma Fine-needle aspiration should be used in conjunction with judicious excisional biopsy. The bilateral and multifocal nature of otherwise occult primary disease argues for total thyroidectomy in this setting.

Cushing’s syndrome is a heterogeneous disorder characterized by numerous physical, psychological and metabolic abnormalities associated with glucocorticoid excess. Left untreated, the condition is associated with considerable morbidity and mortality. 1 The importance of accurate diagnosis and treatment can be inferred from the improved outcome following intervention. However, some individuals do not conform to traditional investigative approaches, presenting a diagnostic trap for the unwary. During the last

A 39-year-old man presented with lower limb muscle pains and weakness which had progressed rapidly over the preceding 2 weeks. Immediately prior to hospital admission he was unable to stand unaided. There had been no disturbance of bulbar, sensory or sphincter function and he reported no recent gastrointestinal symptoms. Medical history included colitis, which was quiescent. His only regular medication was olsalazine. On examination, he was normotensive (and remained so throughout his admission). There was no rash. Cardiovascular, respiratory and abdominal examinations were normal. Neurological examination revealed generalised weakness in all four limbs, most marked proximally. Tendon reflexes were preserved. Plantar response was flexor. Examination of cranial nerves was normal. Laboratory investigations revealed a serum potassium of 1.8 mmol/l. Serum sodium, urea and creatinine were within normal limits. Creatine kinase was 10 719 IU/l. A quadriceps muscle biopsy was performed and the histology is shown in figure 1. Further investigations included an abdominal ultrasound scan, following which computed tomography (CT) of the abdomen was performed (figure 2). A 24-hour urine collection for catecholamines was undertaken (table). View this table: Table Levels of free …

Oligodeoxynucleotides with unmethylated CpG motifs are immunostimulatory. Chloroquine and a number of structural analogs specifically and powerfully inhibit this effect at nanomolar concentrations. We explored the mechanism of this inhibition, with 4-aminoquinolines, quinacrine, 9-aminoacridines, and novel dibasic analogs, many of which are fluorescent. WEHI 231 murine B-lymphoma cells accumulated analogs up to a concentration several hundredfold higher than the medium. Uptake was rapid, nonsaturable, reversible, and partially inhibited by monensin, an agent that collapses pH gradients within cells. Uptake did not correlate highly with efficacy as inhibitors of CpG-oligodeoxynucleotide (ODN)-induced effects, suggesting that analogs act by a specific action. Confocal microscopy revealed analogs concentrating in large peripheral organelles. CpG-ODN is taken up by cells into acidified, small, perinuclear vesicles. This uptake is thought to be necessary for immunostimulatory activity. Cellular uptake of fluorescent CpG-ODN was not inhibited by the analogs. The pH of intracellular CpG-ODN (6. 4) was not affected by analogs at the concentration required for inhibition, but pH was increased by higher concentrations. UV spectroscopy revealed no binding of analogs to CpG-ODN. Nuclear Overhauser effect spectroscopy revealed that an analog bound to phosphatidylcholine vesicles, with the ring structure of the analog buried within the lipid and the side chain facing the aqueous environment. We conclude that the analogs do not inhibit the action of CpG-ODN by preventing the uptake or acidification of CpG-ODN. It seems more likely that the analogs inhibit the efficacy of CpG-ODN by a specific action within acidified vesicles, possibly at the interface of a phospholipid membrane.

A systematic analysis of peptide nucleic acid (PNA) complexes deposited in the Protein Data Bank has been carried out using a set of contiguous atom torsion angle definitions. The analysis is complemented by molecular mechanics adiabatic potential energy calculations on hybrid PNA-nucleic acid model systems. Hitherto unobserved correlations in the values of the (alpha and epsilon) dihedral angles flanking the backbone secondary amide bond are found. This dihedral coupling forms the basis of a PNA backbone conformation classification scheme. Six conformations are thus characterised in experimental structures. Helix morphology is found to exert a significant influence on backbone conformation and flexibility: Watson-Crick PNA strands in complexes with DNA and RNA, that possess A-like base-pair stacking, adopt backbone conformations distinct from those in PNA.DNA-PNA triplex and PNA-PNA duplex P-helix forms. Solvation effects on Watson-Crick PNA backbone conformation in heterotriplexes are discussed and the possible involvement of inter-conformational transitions and dihedral angle uncoupling in asymmetric heteroduplex base-pair breathing is suggested.

We describe four pregnancies in two families in which mild hypophosphatasia, apparently transmitted as an autosomal dominant trait, manifested in utero as severe long bone bowing. Postnatally, there was spontaneous improvement of the skeletal defects. Recognition of this presentation for hypophosphatasia by family investigation and assessment of the fetal skeleton for degree of ossification and chest size using ultrasonography is important. The prognosis for this condition is considerably better than for more severe forms of hypophosphatasia and for many other disorders that cause skeletal defects with long bone bowing in utero.

To determine whether supplementation of vitamin A and/or zinc (Zn) improved serum levels of these nutrients and/or height and weight gains in preschool children, 22 to 66 months, living in Belize, Central America.Subjects received either Zn, vitamin A, Zn and vitamin A or a placebo, (70 mg Zn and/or 3030 RE vitamin A, once per week) for 6 months in a 2x2 factorial design. Forty-three children, from a population of 104 prescreened, completed the study; they were selected, prior to treatment, for low/marginal serum concentrations of these micronutrients.Serum Zn levels were greater (16%, p0.001) for those who received Zn. In contrast, after vitamin A treatment there were no differences in serum vitamin A among groups. Although increases in height (+4.4 cm, p0.001) and weight (+0.79 kg, p0.001), compared with baseline values, were numerically greatest for children who received both supplements, only the vitamin A supplementation effect was significant, resulting in increased height (+1.4 cm, p0.002) and greater weight gain (+0.15 kg, p0.03) compared to those receiving no vitamin A. Vitamin A supplementation alone significantly increased (p0.001) hemoglobin concentration.The results suggest that the preschool children in this study, prescreened for low/marginal serum concentrations from a larger population prior to treatment, were enduring inadequate vitamin A and, to a lesser degree, Zn nutriture. Height and weight gain were significantly increased in the subjects who received a single weekly supplement 3030 RE of vitamin A.

Although the physiological underpinnings of critical power (CP) have yet to be fully elucidated, it has been proposed that CP demarcates the heavy and severe exercise intensity domains and that each domain is associated with a different pattern of metabolic response and mechanism of fatigue. Severe intensity has been defined such that, during exercise at intensities above CP, the slow component of the [Formula: see text] response will drive [Formula: see text] to [Formula: see text] at the point of fatigue. In this Study, two parameters were derived for each of 8 participants: (a) CP, the asymptote of the relationship between power and time to exhaustion, and (b) a related parameter, CP′, the asymptote of the relationship between power and time to [Formula: see text] CP′ theoretically represents the threshold intensity above which [Formula: see text] will be elicited during exercise of sufficient duration. Participants performed two exhaustive tests at CP. There were three important findings: First, there was a practice effect on time to exhaustion at CP, and times increased 27% in the second test. Second, both CP and CP′ could be obtained with good precision. Third, and most important, CP was equal to CP′, thereby providing a physiological description of the mathematically derived CP parameter. It was concluded that [Formula: see text] cannot be elicited at intensities equal to or less than CP. Key words: cycle ergometry, endurance, exercise

Cobb's collar or Moormann's ring is a stricture of the bulbar urethra which is largely unrecognised but has considerable relevance urologically as the site of congenital or post-instrumental strictures. The history, anatomy, embryology and surgical importance are reported.

The diagnosis of systemic candidiasis in ill high-risk neonates is often delayed as there are no specific clinical features and the significance of positive cultures for Candida species may be uncertain. Early diagnosis and treatment is essential to reduce mortality and may be aided by ultrasound examination of the commonly involved organs — The brain and kidneys. In this paper we describe 2 cases where the diagnosis was first raised following ultrasound examination, and review the spectrum of abnormalities seen on renal and cranial ultrasound examination. We emphasise the importance of using this imaging technique in the high-risk neonate in initiating earlier diagnosis and treatment, or in establishing the significance or otherwise of positive cultures.

Since 1990 (i.e., the year in which the number of abortions was highest), the annual number of abortions in the United States has decreased by 15%.This report summarizes and reviews information reported to CDC regarding legal induced abortions obtained in the United States during 1995.For each year since 1969, CDC has compiled abortion data received from 52 reporting areas: 50 states, the District of Columbia, and New York City.In 1995, a total of 1,210,883 legal abortions were reported to CDC, representing a 4.5% decrease from the number reported for 1994. The abortion ratio was 311 legal induced abortions per 1,000 live births, and the abortion rate was 20 per 1,000 women aged 15-44 years, the lowest ratio and rate recorded since 1975. Women who were undergoing an abortion were more likely to be young, white, and unmarried; most were obtaining an abortion for the first time. Approximately half of all abortions (54%) were performed ator =8 weeks of gestation, and approximately 88% were performed before 13 weeks. Approximately 16% of abortions were performed at the earliest weeks of gestation (or =6 weeks), approximately 17% at 7 weeks of gestation, and approximately 21% at 8 weeks of gestation. Few abortions were provided after 15 weeks of gestation -- approximately 4% of abortions were obtained at 16-20 weeks, and 1.4% were obtained ator =21 weeks. Younger women (i.e., women agedor =24 years) were more likely to obtain abortions later in pregnancy than were older women.Since 1990, the number of abortions has declined each year. Since 1987, the abortion-to-live-birth ratio has declined; in 1995, it was the lowest recorded since 1975. This decrease in the abortion ratio reflects a trend that a lower proportion of pregnant women obtain induced abortion.The number and characteristics of women who obtain abortions in the United States should continue to be monitored so that trends in induced abortion can be assessed, efforts to prevent unintended pregnancy can be evaluated, and the preventable causes of morbidity and mortality associated with abortions can be identified and reduced.

Rigid-body motions are determined from a 1 ns molecular dynamics simulation of the unit cell of orthorhombic hen egg-white lysozyme and their contribution to X-ray diffuse scattering intensities are examined. Using a dynamical cluster technique, groups of backbone atoms that move as approximately rigid bodies are derived from the intramolecular interatomic fluctuation matrix. These groups tend to be local in the sequence or connected by disulphide bonds, and contain on average five residues each, X-ray diffuse scattering patterns, which are sensitive to collective motions, are calculated from the full simulation trajectory (including all the protein degrees of freedom). The results reproduce the main features of the experimental scattering. Diffuse scattering is also calculated from fitted trajectories of the rigid bodies. The full simulation diffuse scattering and atomic displacements are found to be well reproduced by a model in which the backbone atoms form the rigid groups determined using the dynamical cluster technique and the individual side-chains behave as separate rigid bodies: the resulting R-factor with the full simulation scattering is 5%. Quantitatively poorer agreement is obtained from trajectories in which the secondary structural elements of the protein are considered rigid. Rigid whole-molecule and domain motions make only minor contributions to the protein atom displacements. Finally, correlations in the interatomic fluctuations are examined directly using a canonical method.

The antibody M alpha2-3 neutralizes the functional, acetylcholine receptor binding activity of its antigen, neurotoxin alpha, and exhibits several other properties in common with the receptor itself. We present here the results of calculations examining the three-dimensional structure of the toxin alpha:M alpha2-3 complex. The antigen structure, determined by nuclear magnetic resonance spectroscopy, was docked to models of the variable fragment of the antibody combining site by using a method based on surface complementarity and maximization of buried surface area while taking into account the possibility of conformational change on complexation. Extensive experimental information on the location of the functional epitope was incorporated into the analysis and used to screen candidate geometries of the complex resulting from the modeling. Eight plausible structures that are in accord with the experimental data were derived. Common structural features of the models are discussed, and residues of the antibody-combining site that are expected to play important roles in complexation are identified. In particular, three epitope residues that, according to mutagenesis experiments, make particularly strong contributions to the binding, interact excentrically and do not make contact with the central loops of the combining site, L3 and H3.

The Healthy People 2000: National Health Promotion and Disease Prevention Objectives specifies goals of no more than 3.3 maternal deaths per 100,000 live births overall and no more than 5.0 maternal deaths per 100,000 live births among black women; as of 1990, these goals had not been met. In addition, race-specific differences between black women and white women persist in the risk for pregnancy-related death.This report summarizes surveillance data for pregnancy-related deaths in the United States for 1987-1990.The National Pregnancy Mortality Surveillance System was initiated in 1988 by CDC in collaboration with the CDC/American College of Obstetricians and Gynecologists Maternal Mortality Study Group. Health departments in the 50 states, the District of Columbia, and New York City provided CDC with copies of death certificates and available linked outcome records (i.e., birth certificates or fetal death records) of all identified pregnancy-related deaths.During 1987-1990, 1,459 deaths were determined to be pregnancy-related. The overall pregnancy-related mortality ratio was 9.2 deaths per 100,000 live births. The pregnancy-related mortality ratio for black women was consistently higher than for white women for every risk factor examined by race. The disparity between pregnancy-related mortality ratios for black women and white women increased from 3.4 times greater in 1987 to 4.1 times greater in 1990. Older women, particularly women agedor =35 years, were at increased risk for pregnancy-related death. The gestational age-adjusted risk for pregnancy-related death was 7.7 times higher for women who received no prenatal care than for women who received "adequate" prenatal care. The distribution of the causes of death differed depending on the pregnancy outcome; for women who died following a live birth (i.e., 55% of the deaths), the leading causes of death were pregnancy-induced hypertension complications, pulmonary embolism, and hemorrhage.Pregnancy-related mortality ratios for black women continued, as noted in previously published surveillance reports, to be three to four times higher than those for white women. The risk factors evaluated in this analysis confirmed the disparity in pregnancy-related mortality between white women and black women, but the reason(s) for this difference could not be determined from the available information.Continued surveillance and additional studies should be conducted to assess the magnitude of pregnancy-related mortality, to identify those differences that contribute to the continuing race-specific disparity in pregnancy-related mortality, and to provide information that policy makers can use to develop effective strategies to prevent pregnancy-related mortality for all women.

From 1991 through 1994, the number of legal induced abortions reported to CDC declined each year byor =5% from the number reported for the preceding year.This report summarizes and reviews information reported to CDC regarding legal induced abortions obtained in the United States during 1993 and 1994. This analysis also includes recently reported abortion-related deaths that occurred during 1991.For each year since 1969, CDC has compiled abortion data received from 52 reporting areas: 50 states, the District of Columbia, and New York City.In 1993, 1,330,414 legal abortions were reported to CDC, representing a 2.1% decrease from the number reported for 1992; in 1994, 1,267,415 abortions were reported, representing a 4.7% decrease from the number for 1993. In 1993 and 1994, the abortion ratio was 334 and 321 legal induced abortions per 1,000 live births, respectively. In 1993, the abortion rate was 22 per 1,000 women aged 15-44 years; in 1994, this rate declined to 21 per 1,000 women. Women who were undergoing an abortion were more likely to be young, white, and unmarried; most were obtaining an abortion for the first time. More than half of all abortions (52%-54%) were performed ator =8 weeks of gestation, and approximately 88% were before 13 weeks. Approximately 15%-16% of abortions were performed ator =6 weeks of gestation, 16% were performed at 7 weeks, and 22% at 8 weeks. Younger women (i.e., women agedor =19 years) were more likely to obtain abortions later in pregnancy than were older women. In 1991, 12 women died as a result of induced abortion: 11 of these deaths were related to legal abortion and one to illegal abortion. During 1991, the case-fatality rate of legal induced abortion was 0.8 abortion-related deaths per 100,000 legal induced abortions.Since 1990, the number of abortions has declined each year. Since 1987, the abortion-to-live-birth ratio also has declined; in 1994, it was the lowest recorded since 1977. This decrease in the abortion ratio reflected the lower proportion of pregnant women who obtained an induced abortion. As in previous years, deaths related to legal induced abortions occurred rarely (i.e., approximately one death per 100,000 legal induced abortions).The number and characteristics of women who obtain abortions in the United States should continue to be monitored so that trends in induced abortion can be assessed, efforts to prevent unintended pregnancy can be evaluated, and the preventable causes of morbidity and mortality associated with abortions can be identified and reduced.