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1.  Risk for obesity in adolescence starts in early childhood 
The objective of this study was to assess the predictive value of body mass index (BMI) at earlier ages on risk of overweight/obesity at age of 11 years.
Study Design
This is a longitudinal study of 907 children from birth to age of 11 years. Predictors include BMI at earlier ages and outcome is overweight/obesity status at age of 11 years. Analyses were adjusted for covariates known to affect BMI.
At 11 years, 17% were overweight and 25% were obese. Children whose BMI was measured as ≥85th percentile once at preschool age had a twofold risk for overweight/obesity at 11 years of age. Risk increased by 11-fold if a child's BMI measured was noted more than once during this age. During early elementary years, if a child's BMI was>85th percentile once, risk for overweight/obesity at 11 years was fivefold and increased by 72-fold if noted more than two times. During late elementary years, if a child's BMI was>85th percentile once, risk for overweight/obesity was 26-fold and increased by 351-fold if noted more than two times. Risk of overweight/obesity at 11 years was noted with higher maternal prepregnancy weight, higher birth weight, female gender and increased television viewing.
Children in higher BMI categories at young ages have a higher risk of overweight/obesity at 11 years of age. Effect size was greater for measurements taken closer to 11 years of age. Pediatricians need to identify children at-risk for adolescent obesity and initiate counseling and intervention at earlier ages.
PMCID: PMC3717579  PMID: 21415836
overweight; obesity; preschool; early elementary; late elementary
2.  Invasive aspergillosis in an immunocompetent patient with fever and a cardiac mass 
Infectious Disease Reports  2011;3(2):e12.
Invasive aspergillosis is an often fatal disease that usually occurs in immunocompromised patients. We report a case of invasive aspergillosis presenting as a febrile respiratory infection with a cardiac mass in an immunocompetent patient. Invasive asper-gillosis should be considered in the differential diagnosis of an otherwise undiagnosed invasive febrile respiratory illness, even in immunocompetent patients. Echocardiography should be performed to evaluate for endocarditis in such cases. Prompt initiation of appropriate antifungal therapy is warranted, even before the diagnosis of invasive aspergillosis is confirmed.
PMCID: PMC3892591  PMID: 24470909
invasive aspergillosis; endocarditis; immunocompetent.
3.  Neonatal Neurobehavior Predicts Medical and Behavioral Outcome 
Pediatrics  2009;125(1):e90-e98.
This study examined the NICU Network Neurobehavioral Scale (NNNS) as a predictor of negative medical and behavioral findings one month to 4½ years of age.
. The sample included 1248 mother-infant dyads (42% born <37 weeks’ gestational age) participating in a longitudinal study of the effects of prenatal substance exposure on child development. Mothers were recruited at 4 urban university-based centers and were mostly African-American and on public assistance. At 1 month of age, infants were tested with the NICU Network Neurobehavioral Scale (NNNS). Latent Profile Analysis (LPA) was carried out on NNNS summary scales to identify discrete behavioral profiles. The validity of the NNNS was examined using logistic regression to predict prenatal drug exposure, medical and developmental outcomes through 4½ years of age including adjustment for gestational age and socioeconomic status (SES).
. Five discrete behavioral profiles were reliably identified with the most extreme negative profile found in 5.8% of the infants. The profiles showed statistically significant associations with prenatal drug exposure, gestational age and birthweight, head ultrasound, neurological and brain disease findings and abnormal scores on measures of behavior problems, school readiness and IQ through 4½ years of age.
The NNNS may be useful to identify infant behavioral needs to be targeted in well-baby pediatric care, as well as for referrals to community based early intervention services.
PMCID: PMC2873896  PMID: 19969621
NNNS; neonatal assessment; neurobehavioral; developmental outcomes; in utero drug exposure; latent profile analysis
5.  Infant colic and feeding difficulties 
Archives of Disease in Childhood  2004;89(10):908-912.
Aims: To examine the relation between colic and feeding difficulties and their impact on parental functioning for a primarily clinic referred sample.
Methods: Forty three infants (and their mothers) were enrolled between 6 and 8 weeks of age. Infants were divided into two groups, colic (n = 19) and comparison (n = 24), based on a modified Wessel rule of three criteria for colic. Families were assessed at two visits; one occurred in the laboratory and one occurred in a paediatric radiology office. Outcome measures included the clinical assessment of infant oral motor skills, behavioural observation of mother-infant feeding interactions, maternal questionnaires on infant crying, sleeping and feeding behaviours, and the occurrence of gastro-oesophageal reflux (GOR) in the infants using abdominal ultrasound.
Results: Infants in the colic group displayed more difficulties with feeding; including disorganised feeding behaviours, less rhythmic nutritive and non-nutritive sucking, more discomfort following feedings, and lower responsiveness during feeding interactions. Infants in the colic group also had more evidence of GOR based on the number of reflux episodes on abdominal ultrasound as well as maternal report of reflux. Mothers in the colic group reported higher levels of parenting stress.
Conclusions: Results provide the first systematic evidence of feeding problems in a subgroup of infants with colic. Data also illustrate the impact of these difficulties on parental and infant functioning. The association between feeding difficulties and colic suggests the potential for ongoing regulatory problems in infants presenting with clinically significant colic symptoms.
PMCID: PMC1719691  PMID: 15383432
6.  Prenatal drug exposure and maternal and infant feeding behaviour 
Objective: To evaluate feeding difficulties and maternal behaviour during a feeding session with 1 month old infants prenatally exposed to cocaine and/or opiates.
Methods: The study is part of the maternal lifestyle study, which recruited 11 811 subjects at four urban hospitals, then followed 1388 from 1 to 36 months of age. Exposure to cocaine and opiates was determined by maternal interview and meconium assay. At the 1 month clinic visit, biological mothers were videotaped while bottle feeding their infants. This sample included 364 exposed to cocaine, 45 exposed to opiates, 31 exposed to both drugs, and 588 matched comparison infants. Mothers were mostly black, high school educated, and on public assistance. Videotapes were coded without knowledge of exposure status for frequency, duration and quality of infant sucking, arousal, feeding problems, and maternal feeding activity and interaction.
Results: No cocaine effects were found on infant feeding measures, but cocaine-using mothers were less flexible (6.29 v 6.50), less engaged (5.77 v 6.22), and had shorter feeding sessions (638 v 683 seconds). Opiate exposed infants showed prolonged sucking bursts (29 v 20 seconds), fewer pauses (1.6 v 2.2 per minute), more feeding problems (0.55 v 0.38), and increased arousal (2.59 v 2.39). Their mothers showed increased activity (30 v 22), independent of their infants' feeding problems.
Conclusions: Previous concerns about feeding behaviour in cocaine exposed infants may reflect the quality of the feeding interaction rather than infant feeding problems related to prenatal exposure. However, opiate exposed infants and their mothers both contributed to increased arousal and heightened feeding behaviour.
PMCID: PMC1721596  PMID: 12937043
7.  Central and autonomic system signs with in utero drug exposure 
Aims: To determine risk for central nervous system/autonomic nervous system (CNS/ANS) signs following in utero cocaine and opiate exposure.
Methods: A multisite study was designed to determine outcomes of in utero cocaine and opiate exposure. A total of 11 811 maternal/infant dyads were enrolled. Drug exposed (EXP) infants were identified by maternal self report of cocaine or opiate use or by meconium testing. Of 1185 EXP, meconium analysis confirmed exposure in 717 to cocaine (CO) only, 100 to opiates (OP), and 92 to opiates plus cocaine (OP+CO); 276 had insufficient or no meconium to confirm maternal self report. Negative exposure history was confirmed in 7442 by meconium analysis and unconfirmed in 3184. Examiners masked to exposure status, assessed each enrolled infant. Using generalised estimating equations, adjusted odds ratios (OR) and 95% confidence intervals (CI) were estimated for manifesting a constellation of CNS/ANS outcomes and for each sign associated with cocaine and opiate exposure.
Results: Prevalence of CNS/ANS signs was low in CO, and highest in OP+CO. Signs were significantly related to one another. After controlling for confounders, CO was associated with increased risk of manifesting a constellation of CNS/ANS outcomes, OR (95% CI): 1.7 (1.2 to 2.2), independent of OP effect, OR (95% CI): 2.8 (2.1 to 3.7). OP+CO had additive effects, OR (95% CI): 4.8 (2.9 to 7.9). Smoking also increased the risk for the constellation of CNS/ANS signs, OR (95% CI) of 1.3 (1.04 to 1.55) and 1.4 (1.2 to 1.6), respectively, for use of less than half a pack per day and half a pack per day or more.
Conclusion: Cocaine or opiate exposure increases the risk for manifesting a constellation of CNS/ANS outcomes.
PMCID: PMC1721453  PMID: 12193516
8.  Mechanism of Insulin-resistant Glucose Transport Activity in the Enlarged Adipose Cell of the Aged, Obese Rat 
Journal of Clinical Investigation  1982;70(4):780-790.
The effects of increasing cell size on glucose transport activity and metabolism and on the concentrations of glucose transport systems in both the plasma and low density microsomal membranes in isolated adipose cells from the aging rat model of obesity have been examined. Glucose transport activity was assessed by measuring l-arabinose transport and the concentration of glucose transport systems estimated by measuring specific d-glucose-inhibitable cytochalasin B-binding. Basal glucose transport activity increases from 0.3 to 1.4 fmol/cell/min with a 10-fold increase in cell size, but remains constant per unit cellular surface area and is accompanied by a constant 5 pmol of glucose transport systems/mg of membrane protein in the plasma membrane fraction. Maximally insulin-stimulated glucose transport activity, on the other hand, remains constant at 2.3 fmol/cell per min with increasing cell size, but markedly decreases per unit cellular surface area and is accompanied by a decrease from 30 pmol of glucose transport systems/mg of plasma membrane protein to the basal level. These diminished effects of insulin on glucose transport activity and the number of glucose transport systems in the plasma membrane fraction in enlarged cells are paralleled by an 80% decrease in the basal number of glucose transport systems/mg of membrane protein in the low density microsomal membrane fraction, the source of those glucose transport systems appearing in the plasma membrane in response to insulin. The effects of cell size on the metabolism of a low concentration of [1-14C]glucose (0.56 mM) directly parallel those on glucose transport activity and the concentration of glucose transport systems in the plasma membrane fraction, and are not associated with significant alterations in the cell's sensitivity to insulin. Thus, adipose cellular enlargement is accompanied by the development of a marked “insulin resistance” at the glucose transport level, which may be the consequence of a relative depletion of glucose transport systems in the intracellular pool.
PMCID: PMC370286  PMID: 6749903
9.  Isolated Aortocoronary Bypass Operations in Patients Over 70 Years of Age 
Western Journal of Medicine  1980;133(1):15-18.
The early and late morbidity, mortality and beneficial effects of isolated aortocoronary bypass operations in a group of 35 patients 70 years old or older were compared with those factors in patients 50 to 59 years old. The patients in both groups were matched according to the year in which the operation was done and the number of vessels bypassed. Left ventricular function, estimated by the angiographically calculated ejection fraction, was not statistically different in the two groups. Cardiac index, while adequate in both groups, was significantly lower in the older age group. Comparisons were made of “early” events, such as perioperative myocardial infarction, perioperative death and length of post-operative hospital stay; and of “late” events, including myocardial infarction, angina pectoris, congestive heart failure and death, which occurred after patients were discharged from the hospital. The mean length of follow-up of patients was similar in both groups.
In comparing early events in the two groups, there was no statistically significant difference in the incidence of perioperative myocardial infarction, perioperative mortality or mean length of postoperative hospital stays. With regard to late events, there was no statistically significant difference in the incidences of myocardial infarction, angina pectoris or mortality.
PMCID: PMC1272182  PMID: 6971528
Journal of Clinical Investigation  1973;52(4):929-941.
The cellular character of the adipose tissue of 21 nonobese and 78 obese patients has been examined. Adipose cell size (lipid per cell) was determined in three different subcutaneous and deep fat depots in each patient and the total number of adipose cells in the body estimated by division of total body fat by various combinations of the adipose cell sizes at six different sites. Cell number has also been estimated on the basis of various assumed distribution of total fat between the subcutaneous and deep fat depots.
Obese patients, as a group, have larger adipose cells than do nonobese patients; cell size, however, varies considerably among the fat depots of individuals of either group. The variation in cell size exists not only between, but also within subcutaneous and deep sites. Estimates of total adipose cell number for a given individual based upon cell size can, therefore, vary by as much as 85%. On the basis of these studies it is suggested that the total adipose number of an individual is best and most practically estimated, at this time, by division of total body fat by the mean of the adipose cell sizes of at least three subcutaneous sites.
Irrespective of the method by which total adipose cell number is estimated, two patterns of obesity emerge with respect to the cellular character of the adipose tissue mass of these patients: hyperplastic, with increased adipose cell number and normal or increased size, and hypertrophic, with increased cell size alone. These two cellular patterns of obesity are independent of a variety of assumed distributions of fat among the subcutaneous and deep depots. When these different cellular patterns are examined in terms of various aspects of body size, body composition, and the degree, duration, and age of onset of obesity, only the latter uniquely distinguishes the hyperplastic from the hypertrophic: hyperplastic obesity is characterized by an early age of onset, hypertrophic, by a late age of onset. These studies indicate that there are two distinct periods early in life during which hypercellularity of the adipose tissue are most likely to occur: very early within the first few years, and again from age 9 to 13 yr.
PMCID: PMC302341  PMID: 4693656
11.  The effect of insulin upon glucose metabolism by adipose cells of different size 
Journal of Clinical Investigation  1971;50(7):1399-1410.
Glucose metabolism and insulin sensitivity of isolated rat epididymal fat cells and of their delipidated derivatives (“ghosts”) was studied as a function of cellular lipid content (fat cell size), cellular protein content, animal age, and state of nutrition in an effort to examine the relationship of adipose cell size to adipose tissue insulin sensitivity.
In ad libitum-fed rats, basal rates of glucose-1-14C incorporation into CO2 and triglyceride are similar over a wide range of adipose cell size. In contrast, the insulin sensitivity of intact fat cells from rats fed ad libitum is inversely related to their lipid content: the larger the cell, the less the response to insulin. This “resistance” of the enlarged adipose cell to the action of insulin was demonstrated by a reduction in the per cent rise above the basal rate as well as in the absolute rate of glucose oxidation and lipogenesis caused by insulin.
The protein content of fat cells was found to be relatively constant over a wide range of fat cell size. Thus, enlarged insulin “resistant” fat cells contained the same amount of protein as smaller insulin “sensitive” cells.
These relationships between insulin sensitivity and cellular lipid or protein content were true regardless of whether cells of different sizes were obtained from animals of different body weights and ages, or from different portions of the epididymal fat pads of animals of the same weight and age.
Acute delipidation of intact fat cells did not appear to alter these relationships between basal glucose metabolism, insulin sensitivity, and cell size. “Ghosts” prepared from fat cells of widely different sizes metabolized glucose to CO2 and triglyceride at similar rates. The insulin sensitivity of the fat cell “ghost” appeared to be inversely related to the size of the intact cell from which it was derived: the larger the intact cell the less insulin sensitive its “ghost.”
Although the insulin “resistance” of adipose tissue was reversed by weight loss and reduction of fat cell size, these studies also demonstrate that the insulin sensitivity of adipose cells of similar sizes can vary widely depending upon the state of nutrition and growth of the animal. Thus, factors other than cell size can also influence the insulin sensitivity of the adipose tissue.
PMCID: PMC292078  PMID: 5090056
12.  Experimental obesity in man: cellular character of the adipose tissue 
Journal of Clinical Investigation  1971;50(5):1005-1011.
Studies of adipose tissue cellularity were carried out in a group of nonobese adult male volunteers who gained 15-25% of their body weight as the result of prolonged high caloric intake. Adipose cell size (lipid content per cell) was determined in tissue obtained from three subcutaneous sites (gluteal, anterior abdominal wall, and triceps) and total adipose cell number estimated from measurement of total body fat.
Five experimental subjects gained an average of 16.2 kg of body weight, of which 10.4 kg was determined to be fat. Expansion of the adipose mass was accompanied by a significant and relatively uniform increase in fat cell size in each subcutaneous site tested. Total adipose cell number did not change as a result of weight gain and expansion of the adipose depot in adult life. Subsequent loss of weight and restoration of original body fat was associated with a reduction in adipose cell size at each subcutaneous site, but no change in total number. In two control subjects who neither gained nor lost weight there were no changes in total adipose cell number or cell size. These observations suggest that expansion and retraction of the adipose depot in adult life is accompanied by changes in adipose cell size only.
Significant differences in both the size and total number of adipose cells were observed between subjects in both the experimental and control groups. In addition, within individuals of both groups there were significant differences in cell size when adipose cells from the three subcutaneous sites were compared. These findings indicate that wide variations in adipose cell size and number exist in nonobese individuals having similar adipose depot sizes.
PMCID: PMC292021  PMID: 5552403
13.  The Extent of Role Differentiation among Hospitals 
Health Services Research  1971;6(1):15-38.
The case mix of 65 western Pennsylvania hospitals is studied from Hospital Utilization Project data comprising a quarter of a million patient records, and five measures are constructed to describe the inpatient population on the basis of diagnoses and surgical procedures. The case-mix variation defined by these measures is then analyzed in a series of regressions on selected institutional characteristics and on demographic and locational variables, revealing urban vs. rural location to be an important determinant. While size, number of facilities and services, and teaching status of a hospital are shown to be correlated with case mix, they are found to explain too small a portion of the variation to be satisfactory surrogates for case mix.
PMCID: PMC1067308  PMID: 5569225
14.  The role of adipose cell size and adipose tissue insulin sensitivity in the carbohydrate intolerance of human obesity 
Journal of Clinical Investigation  1968;47(1):153-165.
Glucose metabolism and insulin sensitivity of isolated human adipose tissue was studied as a function of adipose cell size and number. Glucose metabolism by these tissues was closely related to the number of cells in the fragment, irrespective of cell size. Adipose cells of obese individuals metabolized glucose to carbon dioxide and triglyceride at rates similar to adipose cells of nonobese subjects. In contrast, insulin responsiveness of adipose tissue was dependent upon adipose cell size. The larger its adipose cells the less insulin sensitive was the tissue. Thus, adipose tissue of obese subjects, with enlarged cells, showed a diminished response to insulin. After weight loss and reduction in adipose cell size, insulin sensitivity of the adipose tissue of obese patients was restored to normal. When adipose tissue of obese individuals showed impaired responsiveness to insulin, their plasma insulin levels, after oral glucose, were elevated. Weight loss and reduction in adipose cell size restored plasma insulin concentration to normal, concomitant with the return of normal tissue insulin sensitivity.
PMCID: PMC297156  PMID: 16695937
California Medicine  1951;75(4):296-299.
Cerebral concussion is a physiological disturbance in the brain that follows a blow on the head. The cardinal symptom is a disturbance in consciousness varying from a complete loss of consciousness to a dazed state. The phenomenon is self-limited and completely reversible.
In cerebral contusion there is actual injury to the brain. The symptoms that result vary according to the amount and location of the damage. A very small amount of damage in certain areas of the brain may be fatal, while extensive damage in other areas will be survived.
Even when a patient is unconscious after a head injury, certain simple neurologic tests can be done to determine with some accuracy the extent and location of brain damage. When the patient regains consciousness, further bedside tests can be carried out to increase the accuracy of diagnosis.
Careful observation of the patient at frequent intervals is necessary to judicious application of appropriate treatment. The physician must be on the alert constantly for signs of intracranial hemorrhage and should be ready to intervene surgically if necessary.
In most cases of injury to the head, treatment consists of supplying to the patient elements that are necessary to maintain physiologic conditions and of combating disorders arising from specific injuries to the brain.
PMCID: PMC1520972  PMID: 14879278

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