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Sanfilippo syndrome is a group of rare, complex, and progressive neurodegenerative lysosomal storage disorders that is characterized by childhood dementia. The clinical management of patients with progressive neurological decline and multisystem involvement requires a multidisciplinary team with experience in the management of neurodegenerative disorders. Best practice guidelines for the clinical management of patients with these types of rare disorders are critical to ensure prompt diagnosis and initiation of appropriate care. However, there are no published standard global clinical care guidelines for patients with Sanfilippo syndrome. To address this, a literature review was conducted to evaluate the current evidence base and to identify evidence gaps. The findings were reviewed by an international steering committee composed of clinical experts with extensive experience in managing patients with Sanfilippo syndrome. The goal was to create a consensus set of basic clinical guidelines that will be accessible to and informed by clinicians globally, as well as providing a practical resource for families to share with their local care team who may not have experience with this rare disease. This review distills 178 guideline statements into an easily digestible document that provides evidence-based, expert-led recommendations for how to approach common management challenges and appropriate monitoring schedules in the care of patients with Sanfilippo syndrome.

International audience; In this trans-ethnic multi-omic study, we reinterpret the genetic architecture of blood pressure to identify genes, tissues, phenomes and medication contexts of blood pressure homeostasis. We discovered 208 novel common blood pressure SNPs and 53 rare variants in genome-wide association studies of systolic, diastolic and pulse pressure in up to 776,078 participants from the Million Veteran Program (MVP) and collaborating studies, with analysis of the blood pressure clinical phenome in MVP. Our transcriptome-wide association study detected 4,043 blood pressure associations with genetically predicted gene expression of 840 genes in 45 tissues, and mouse renal single-cell RNA sequencing identified upregulated blood pressure genes in kidney tubule cells.

Helen A Lane, Jamie C Smith, J Stephen DaviesDepartment of Endocrinology, University of Wales College of Medicine, Heath Park, Cardiff, Wales, UKAbstract: Initially considered as a semipermeable barrier separating lumen from vessel wall, the endothelium is now recognised as a complex endocrine organ responsible for a variety of physiological processes vital for vascular homeostasis. These include the regulation of vascular tone, luminal diameter, and blood flow; hemostasis and thrombolysis; platelet and leucocyte vessel-wall interactions; the regulation of vascular permeability; and tissue growth and remodelling. The endothelium modulates arterial stiffness, which precedes overt atherosclerosis and is an independent predictor of cardiovascular events. Unsurprisingly, dysfunction of the endothelium may be considered as an early and potentially reversible step in the process of atherogenesis and numerous methods have been developed to assess endothelial status and large artery stiffness. Methodology includes flow-mediated dilatation of the brachial artery, assessment of coronary flow reserve, carotid intimamedia thickness, pulse wave analysis, pulse wave velocity, and plethysmography. This review outlines the various modalities, indications, and limitations of available methods to assess arterial dysfunction and vascular risk.Keywords: endothelial function, vascular risk, vascular stiffness

In patients with cancer, adrenal enlargement due to either metastatic disease or diffuse non-metastatic hyperplasia is increasingly recognized with modern imaging techniques. Dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis, characterized by non-suppressible hypercortisolism, has also been described in neoplasia in the absence of ectopic adrenocorticotrophic hormone (ACTH) production. In the majority of cases of malignancy-associated hypercortisolism, it might be expected that the presence of malignant disease would be clinically apparent, thus rendering a detailed endocrinological evaluation of the HPA axis unnecessary. However, in the present case we describe a patient with occult malignancy presenting with bilateral adrenocortical enlargement and non-suppressible hypercortisolism that was not due to the ectopic ACTH syndrome. There were no clinical Cushingoid features other than hypertension and new-onset diabetes mellitus. Detailed diagnostic investigations for the possibility of Cushing's syndrome were performed before the underlying diagnosis of gastric adenocarcinoma eventually became apparent. Characteristics and potential mechanisms of non-suppressible hypercortisolism in cancer are discussed. We believe that this scenario will occur with greater frequency in the future, given the increasing early use of sophisticated high-resolution imaging for the evaluation of suspected intra-abdominal pathology.

Although GH deficiency may underlie the increased cardiovascular risk in adult hypopituitarism, other coexisting hormonal deficiencies and/or unphysiological hormone replacement may contribute. l-Deamino-8-d-arginine (DDAVP), when administered parenterally, potentiates hemostasis by increasing plasma procoagulant factors. We investigated whether chronic intranasal DDAVP therapy influences clotting factors (plasma fibrinogen, factor VIII, and von Willebrand factor antigen) and endothelial function (flow-mediated dilation of the brachial artery) in 30 GH-treated hypopituitary subjects, including both DDAVP-treated subjects (group A) (mean age, 46 ± 11 yr) and vasopressin-sufficient subjects (group B) (mean age, 47 ± 16 yr). Fifteen healthy controls (group C) (mean age, 48 ± 12 yr) were also studied. All hypopituitary patients were receiving stable GH replacement (median duration, 19 months). Comparing the three groups, concentrations of fibrinogen (mean ± sd) (A, 3.3 ± 1.0 g/liter vs. B, 3.5 ± 0.9 vs. C, 2.6 ± 0.8, P < 0.05), factor VIII (A, 130% ± 30% vs. B, 128% ± 30% vs. C, 104% ± 35%, P < 0.05) and von Willebrand factor antigen (A, 124% ± 35% vs. B, 134% ± 45% vs. C, 93% ± 36%, P < 0.05) were higher in hypopituitary subjects, compared with controls. However, there were no differences in clotting factors between groups A and B. Flow-mediated dilation did not differ significantly between the two hypopituitary groups (A, 5.9% ± 2.0% vs. B, 4.7% ± 1.6%) and was similar to that in the control group (C, 5.7% ± 2.1%). In conclusion, although endothelium-dependent vasodilation is intact in GH-treated hypopituitary adults, elevated concentrations of hemostatic markers suggest the persistence of a prothrombotic tendency and endothelial dysfunction. Intranasal DDAVP does not appear to influence this proatherogenic profile in hypopituitary adults with vasopressin deficiency.

Sex hormones appear to play a pivotal role in determining cardiovascular risk. Androgen deprivation therapy for males with prostate cancer results in a hypogonadal state that may have important, but as yet undetermined, effects on the vasculature. We studied the effects of androgen deprivation therapy on large artery stiffness in 22 prostate cancer patients (mean age, 67 +/- 8 yr) over a 6-month period. Arterial stiffness was assessed using pulse-wave analysis, a technique that measures peripheral arterial pressure waveforms and generates corresponding central aortic waveforms. This allows determination of the augmentation of central pressure resulting from wave reflection and the augmentation index, a measure of large artery stiffness. Body compositional changes were assessed using bioelectrical impedance analysis. Fasting lipids, glucose, insulin, testosterone, and estradiol were measured. After a 3-month treatment period, the augmentation index increased from 24 +/- 6% (mean +/- SD) at baseline to 29 +/- 9% (P = 0.003) despite no change in peripheral blood pressure. Timing of wave reflection was reduced from 137 +/- 7 to 129 +/- 10 msec (P = 0.003). Fat mass increased from 20.2 +/- 9.4 to 21.9 +/- 9.6 kg (P = 0.008), whereas lean body mass decreased from 63.2 +/- 6.8 to 61.5 +/- 6.0 kg (P = 0.016). There were no changes in lipids or glucose during treatment. Median serum insulin rose from 11.8 (range, 5.6-49.1) to 15.1 (range, 7.3-83.2) mU/liter at 1 month (P = 0.021) and to 19.3 (range, 0-85.0 mU/liter by 3 months (P = 0.020). There was a correlation between the changes in fat mass and insulin concentration over the 3-month period (r = 0.56; P = 0.013). In a subgroup of patients whose treatment was discontinued after 3 months, the augmentation index decreased from 31 +/- 7% at 3 months to 29 +/- 5% by 6 months, in contrast to patients receiving continuing treatment in whom the augmentation index remained elevated at 6 months compared with baseline (P = 0.043). These data indicate that induced hypogonadism in males with prostate cancer results in a rise in the augmentation of central arterial pressure, suggesting large artery stiffening. Adverse body compositional changes associated with rising insulin concentrations suggest reduced insulin sensitivity. These adverse hemodynamic and metabolic effects may increase cardiovascular risk in this patient group.

Primary hyperparathyroidism (PHPT) is associated with increased cardiovascular risk, although the mechanisms involved remain unclear. Recent evidence has shown increased pulse pressure to be a powerful predictor of cardiovascular events. As increases in pulse pressure are due largely to arterial stiffening, we measured arterial stiffness in 21 subjects with PHPT (18 women and 3 men; 46-71 yr old) and 21 age- and sex-matched healthy controls using pulse wave analysis, a technique that measures peripheral arterial pressure waveforms and generates corresponding central aortic waveforms. This allows determination of the augmentation of central pressure resulting from wave reflection and augmentation index, a measure of vessel stiffness. Metabolic parameters were also measured. The serum calcium level among PHPT subjects was (mean +/- SD) 2.74+/-0.14 mmol/L. pulse wave analysis showed that both augmentation and the augmentation index were significantly higher in the PHPT group vs. controls [16+/-5 vs. 10+/-4 mm Hg (P < 0.001) and 36+/-9% vs. 25+/-6% (P < 0.001)] despite comparable brachial systolic pressures between groups (136+/-13 vs. 134+/-18 mm Hg). Patients with PHPT had higher fasting serum insulin levels [median (range), 15.8 (7.4-39.4) vs. 11.6 (5.1-23) mU/L; P < 0.05] and triglyceride (1.6+/-0.6 vs. 1.2+/-0.4 mmol/L; P < 0.05), but lower high density lipoprotein cholesterol (1.4+/-0.4 vs. 1.6+/-0.3 mmol/L; P < 0.05). These data indicate that subjects with mild PHPT (calcium

The purpose of this study was to evaluate critical power (W(CP)) as an indicator of aerobic fitness in trained cyclists, and to determine its relationship to cycling time trial (TT) performance. Thirteen competitive USCF category 2 or 3 cyclists provided season's best 40 km TT times (mean [SD]) time = 59.6 min (3.1), and performed two 17 km TT under controlled conditions (26.6 min [1.1]). Ventilatory threshold (VT) and VO2max were determined from a maximal incremental test. W(CP) was calculated using the results of four all-out constant power tests. Mean W(CP) was 299 (61) W or 4.1 W x kg(-1), VT was 3616 (750) ml x min(-1) or 49.8 ml x kg(-1) x min(-1) (7.5), and VO2max was 4596 ml x min(-1) or 63.5 ml x kg(-1) x min(-1) (8.0). W(CP) was strongly related to VT and VO2max, demonstrating that it can serve as a measure of aerobic fitness in this population. Expressions of W(CP) were slightly to considerably more highly related to 17 km and 40 km TT performances (r = -0.77 to -0.91) than were expressions of VT and VO2max (r = -0.71 to -0.87). It is concluded that W(CP) provides an aerobic fitness measure for competitive cyclists which can be obtained without invasive testing. In addition, W(CP) is strongly related to the TT performance of competitive cyclists.

The scientific community has recently focused its concerns on possible developmental delays in infants exposed to methylmercury via maternal fish consumption. In this study, the authors reported levels of methylmercury in hair specimens that corresponded to 2820 monthly seafood consumption diaries recorded by U.S. women of childbearing age. In this study, the geometric mean hair methylmercury level for diarists who reported some seafood consumption was 0.36 ppm (one geometric standard deviation [GSD] range = 0.14-0.90 ppm); the corresponding value for diarists who reported no seafood consumption was 0.24 ppm (one GSD range = 0.09-0.62 ppm). Therefore, the mean hair methylmercury level associated with seafood consumption was 0.12 ppm (one GSD range = 0.05-0.32 ppm). The results of this study provide evidence that levels of methylmercury in the U.S. population are quite low. There is a significant contribution to hair methylmercury from sources other than seafood. It is not likely that maternal hair methylmercury levels in the range found in our study would be associated with adverse health effects in children.

Congestive heart failure occurring in unoperated patients with otherwise uncomplicated tetralogy of Fallot (TF) is rare. We report the case of a boy who was first diagnosed as having TF when he presented at age 3 years with hypoxia and heart failure. Heart failure improved following an aortopulmonary shunt. We attributed his heart failure to cardiomyopathy associated with severe hypoxia. We believe that this report is the first one that attributes heart failure to hypoxia in an unoperated patient with tetralogy of Fallot.

Facial cooling (FC) elicits a marked bradycardia at rest that appears to be reduced during exercise. This study was done to delineate the effects of exercise mediated central command from those of muscle afferent feedback and sympathetic stimulation on the attenuation of the bradycardic effect of FC during the onset of exercise. Ten healthy subjects (26 +/- 2 yr) were exposed to FC under five different conditions: 1) seated rest on the cycle ergometer, 2) onset of mild exercise (resting HR + 20 beats.min-1), 3) onset of moderate exercise (resting HR + 50 beats.min-1), 4) seated rest on the ergometer during electrical stimulation, and 5) seated rest on the ergometer during a cold immersion test (CT) (one hand immersed in an ice slurry at 0 degree C). The two exercise intensities were presumed to provide different degrees of central command. Electrical stimulation of the quadriceps was assumed to provide isolated muscle afferent feedback, while the CT served as a sympathetic stimulus. Beat-by-beat data were recorded for HR and mean arterial blood pressure for the duration of each test (50 s), and a rating of perceived pain was taken after each FC. FC elicited significant increases in mean arterial pressure during mild and moderate exercise compared with resting control (P0.05) and during moderate exercise compared to exercise without FC (P0.05). Mean decreases in HR during FC were similar for resting control (-12 +/- 3 beats.min-1), electrical stimulation (-10 +/- 3 beats.min-1), and CT (-9 +/- 3 beats.min-1). The HR response to FC during mild exercise (-7 +/- 2 beats.min-1) was significantly different (P0.05) from the rest condition; however, there was no significant bradycardia (-2 +/- 2 beats.min-1; P0.05) during onset of moderate exercise. These findings suggest that the magnitude of cold face-induced bradycardia may be attenuated at exercise onset by neural signals related to the higher levels of central motor command associated with heavier exercise.

Although two thirds or more of patients with microprolactinoma achieve normal serum prolactin levels over the long term after withdrawal of dopamine agonist therapy, there is no agreement on the appropriate duration of treatment, and treatment is not always interrupted. In this retrospective analysis of 89 patients, 84 women and 5 men with a mean age of 33 years, remissions were analyzed in 67 patients treated with 0.5 to 3 mg cabergoline weekly and 22 others given 2.5 to 10 mg bromocriptine daily. The mean duration of therapy was 3.1 years, and patients were followed for at least 1 year after treatment ended. None of the patients received medication other than a dopamine agonist. Seven women discontinued treatment when they became pregnant. All patients were symptomatic and hyperprolactinemic when first seen. Among 57 patients (64%) who had a recurrence after treatment stopped were 46 (81%) who had recurrent symptomatic hyperprolactinemia within 12 months after stopping treatment. The average interval was 9.6 months. Thirty-two patients, 36% of the total, achieved remission after at least 1 year of follow up; the mean duration of remission was 3.6 years. Nearly 85% of these patients remained in remission for longer than 2 years. Four of them were asymptomatic despite being hyperprolactinemic. The 2 dopamine agonists were equally effective. The overall median duration before relapse after discontinuance of treatment was 12 months. Logistic regression analysis failed to demonstrate an association between the risk of recurrence and age at presentation, imaging of an adenoma, or the duration of treatment. When dopamine agonist therapy is abruptly withdrawn after 2 years or longer in patients with microprolactinoma, 30% to 40% achieve long-term remission without side effects. Because symptomatic hyperprolactinemia may develop more than 1 year after treatment stops, long-term follow up is essential.

With the introduction of interventional procedures such as percutaneous mitral valvuloplasty and radiofrequency ablation of left-sided bypass tracts, there has been renewed interest in the technique of transseptal left heart catheterization. We review our experience with 1,279 transseptal catheterizations performed over the last 10 years. The most common indications for transseptal catheterization included direct measurement of left atrial pressure or access to the left ventricle in patients with prosthetic aortic or mitral valves, and in patients undergoing percutaneous mitral valvuloplasty. A total of 17 major complications occurred (1.3%), including cardiac tamponade (15 patients, 1.2%), systemic emboli (1 patient, 0.08%), and death secondary to aortic perforation (0.08%). We conclude that when performed by experienced operators, transseptal left heart catheterization is associated with low morbidity and mortality.

To examine the influence of inositol phosphates on the uptake and absorption of Fe and Zn, Caco-2 cells were grown on either plastic (uptake studies) or porous membranes in bicameral chambers (transport/absorption studies). Caco-2, a human colon adenocarcinoma cell line, was selected as the test cell because it spontaneously differentiates into polarized enterocyte-like cells at confluency. Uptake of Fe (added as Fe-nitrilotriacetate complex) from a calcium-free solution by fully differentiated cells was 37 pmol/cm2. Addition of 10-fold molar excess of individual inositol phosphates (IP3, IP4, IP5 or IP6) decreased Fe solubility by 13 to 25% and reduced Fe uptake by 50 to 65%. The rate of transport of Fe from the apical solution into the basolateral chamber [1.4 +/- 0.1 pmol/(h.cm2)] decreased (34-96%) in proportion to the degree of phosphorylation of the inositol derivative in the apical compartment. Uptake and transepithelial transport of Zn were 246 +/- 5 pmol/cm2 and 23 +/- 1 pmol/(h.cm2), respectively. The solubility, uptake and rate of transport of Zn also decreased in proportion to the degree of phosphorylation of inositol. These results demonstrate the inhibitory influence of IP3-IP6 on the uptake and transport of Fe and Zn and support the usefulness of the Caco-2 human cell line as an appropriate model for evaluating the effects of specific dietary factors on trace metal bioavailability.

In an initial study of 20 fresh ovarian tumour samples, we compared the immunohistochemical positivity of staining of the p53 protein with the presence of missense mutations of the p53 gene. This revealed a prevalence of 50% with a perfect correlation between mutation and immunohistochemical staining. Detection of the p53 protein by immunohistochemistry was, therefore, used as a reliable indicator for the presence of P53 mutation, and was applied to a study of an archival series of 93 ovarian tumours. Positive immunostaining of the p53 protein was observed in 47% of this series. Cox regression was used to assess whether various clinical variables and P53 mutation were related to survival. As a result, it was found that positive staining of the p53 protein was independent of age, tumour differentiation, tumour type, though possibly not stage. There was some evidence that p53 positivity was associated with reduced survival after adjusting for other variables, but the result was not statistically significant.

A newly available carotenoid food-composition database providing specific carotenoid values for > 2300 foods was linked to dietary data on 57 male nonsmokers to examine the association between dietary carotenoid intake and plasma carotenoid concentrations over 3 wk when free-living. Carotenoid intake was estimated from a food-frequency questionnaire (FFQ) and 7 d of food diaries with concurrent analysis of plasma carotenoid concentrations. After adjustment for energy intake, percentage of energy from alcohol, and plasma lipid concentrations, significant diet-plasma correlations for the FFQ and the food diaries (FD) included alpha-carotene (r = 0.29 and 0.43), beta-carotene (r = 0.36 FFQ only), beta-cryptoxanthin (r = 0.46 and 0.44), lutein (r = 0.44 FD only), and lycopene (r = 0.53 FD only). Dietary carotenoid intakes were associated with plasma carotenoid concentrations for all the carotenoids except for beta-carotene when food diaries were used whereas the diet-plasma correlation for the provitamin A carotenoids were consistently significant when the FFQ was used.

Three studies were performed to evaluate the effects of jet lag on factors associated with sport performance. In Study 1, members of the USA Women's Soccer Team traveled to Taiwan; in Study 2, North American students and faculty traveled to Western Europe; and in Study 3, European students traveled to North America. After travel, there was disruption of mood state and a reduction in dynamic strength; peak 5-s power and 30-s work capacity were reduced for 2 days (5-s power: 9.8 vs. 9.0 vs. 9.0 W∙kg−1; 30-s work capacity: 213 vs. 199 vs. 201 J∙kg−1). In these studies, mood state, anaerobic power and capacity, and dynamic strength were affected by rapid transmeridianal travel, and even highly trained athletes suffered from jet lag. However, effects of travel on the variables tested were essentially eliminated after 3 or 4 days. Key words: circadian rhythm, anaerobic power, anaerobic capacity, mood, travel

Previous surveys suggested that young children in Northeast Thailand may benefit from vitamin A and/or zinc supplementation. One hundred thirty-three children aged 6-13 y with marginal plasma retinol (less than 1.05 mumol/L) and Zn (less than 12.2 mumol/L) concentrations participated in a double-blind study. They were randomly assigned and supplemented with either zinc (25 mg/d), vitamin A (1500 RE/d), zinc plus vitamin A, or placebo for 6 mo. Biochemical indices of vitamin A (plasma vitamin A, retinol-binding protein) and zinc status (plasma zinc, alkaline phosphatase) increased significantly. The children had adequate liver stores of vitamin A (relative dose response less than 20%). Zinc supplementation resulted in an improvement in vision restoration time (VRT) in dim light (dark adaptometry). Vitamin A and zinc synergistically normalized conjunctival epithelium as measured by conjunctival impression cytology (CIC). Both functional indices, VRT and CIC, showed significant correlations with plasma zinc and vitamin A, respectively. The data suggest that functional improvements in populations with suboptimal vitamin A and zinc nutriture can be accomplished by supplementation with less than two times the recommended dietary allowance of these nutrients.

ABSTRACI’ We determined serial changes in four major plasma carotenoid fractions (a-carotene, /3-carotene, lutein/ zeaxanthin, and lycopene) in 30 men consuming defined daily doses of carotenoids from foods (broccoli, carrots, or tomato juice) or from purified /3-carotene in capsules (12 or 30 mg) for 6 wk while fed a controlled diet. Compared with baseline, /3carotene increased in the 30- and 12-mg-capsule and carrot groups whereas a-carotene increased in the carrot group and lutein increased in the broccoli group. Lower lutein concentrations in recipients of/3-carotene capsules suggested an interaction between these two carotenoids. Lycopene declined in all groups except the tomato-juice group. Total carotenoid concentration changes only reflected the large increases in /3-carotene concentrations and not the smaller changes observed in other individual carotenoids. Overall, purified /3-carotene produced a greater plasma response than did similar quantities ofcarotenoids from foods sources. However, some foods increased plasma concentrations of certain carotenoids. Am J C/in Nutr l992;55

The collagen VI muscular dystrophies, Bethlem myopathy and Ullrich congenital muscular dystrophy, form a continuum of clinical phenotypes. Glycine mutations in the triple helix have been identified in both Bethlem and Ullrich congenital muscular dystrophy, but it is not known why they cause these different phenotypes.We studied eight new patients who presented with a spectrum of clinical severity, screened the three collagen VI messenger RNA for mutations, and examined collagen VI biosynthesis and the assembly pathway.All eight patients had heterozygous glycine mutations toward the N-terminal end of the triple helix. The mutations produced two assembly phenotypes. In the first patient group, collagen VI dimers accumulated in the cell but not the medium, microfibril formation in the medium was moderately reduced, and the amount of collagen VI in the extracellular matrix was not significantly altered. The second group had more severe assembly defects: some secreted collagen VI tetramers were not disulfide bonded, microfibril formation in the medium was severely compromised, and collagen VI in the extracellular matrix was reduced.These data indicate that collagen VI glycine mutations impair the assembly pathway in different ways and disease severity correlates with the assembly abnormality. In mildly affected patients, normal amounts of collagen VI were deposited in the fibroblast matrix, whereas in patients with moderate-to-severe disability, assembly defects led to a reduced collagen VI fibroblast matrix. This study thus provides an explanation for how different glycine mutations produce a spectrum of clinical severity.

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.

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.

Tracheostomies in children are increasingly performed for chronic medical conditions. There are no published studies reporting the experience of children with a tracheostomy in school. Such information would be valuable in planning the care and education of these children. The aims of this study were to identify those children with a tracheostomy in Nottinghamshire schools and determine the support they were receiving.Questionnaire survey to families and school carers of 11 children with a tracheostomy.All children of school age were in full-time education (five mainstream, five special schools). One preschool child attended a Family Centre. Four had problems finding suitable carers, delaying return to school in three. Four parents were dissatisfied with aspects of the child's experience at school: two felt the teaching staff were unsupportive, one was unhappy with the care of the tracheostomy, and one had problems funding a carer. Ten out of 11 school carers were satisfied with their training; 10 would have liked regular update sessions. The amount of care required varied. Those with complex medical problems in a special school setting needed frequent care, and one had required admission to hospital from school. One child had time off school because of lack of carer availability. Those who were severely disabled had less time off school for ill health after the tracheostomy than before the tracheostomy.Children with tracheostomies can successfully and safely achieve full-time education in both mainstream and special schools. A dedicated multidisciplinary team, including input from the parents, is essential to achieve this goal. Regular revision of skills and information sessions for the teaching staff would be beneficial.

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.

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.

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 primary objective was to estimate prevalence of malnutrition on admission to four hospitals. Secondary objectives included assessing the relationship between nutritional status and length of hospital stay, numbers of new prescriptions, new infections and disease severity.We entered eligible patients according to predefined quotas for elective and emergency admissions to 23 specialties. We measured height, weight, Body Mass Index and anthropometrics, and recorded history of unintentional weight loss. Patients who had lostor = 10% of their body weight, had a Body Mass Index20, or had a Body Mass Index20 with one anthropometric measurement15th centile were considered malnourished.Of 1611 eligible patients, 761 did not participate; 269 were too ill; 256 could not be weighed; and 236 refused consent. Eight hundred and fifty were subsequently evaluated. Prevalence of malnutrition on admission was 20%. Length of stay, new prescriptions and infections and disease severity were significantly higher in the malnourished.One patient in every five admitted to hospital is malnourished. Although this figure is unacceptably high, it may underestimate true prevalence. Malnutrition was associated with increased length of stay, new prescriptions and infections. Malnutrition may also have contributed to disease severity.

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 …

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.

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.

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.