Enhancing medical students' participation in the rural community.
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Community Medicine↗
Biomedical subjects
M Rosenbaum
Publications and source records attributed to M Rosenbaum.
An exploratory investigation of the morphology and biochemistry of cellulite.
Dimpling of the skin of the thighs and buttocks is commonly referred to as cellulite, and it afflicts women much more frequently than men. Whereas many therapies that presume cellulite is caused by an abnormality of adipose tissue have gained recent popularity, the basic pathophysiology of cellulite has not been clearly identified. Theoretically, cellulite could reflect differences in adipose tissue biochemistry or connective tissue structure of affected versus unaffected individuals and/or of affected versus unaffected regions within an individual. We report here on direct experimental examination of these possibilities. Seven healthy adult subjects (five women, two men; four affected, three unaffected) underwent sonography of the thigh, measurement of regional in vivo subcutaneous adipose tissue metabolism (catecholaminergic responsiveness and blood flow) by microdialysis probe studies of the abdomen and the thigh, and full-thickness wedge biopsy of the thigh under local anesthesia. The presence of cellulite was defined as evidence of dimpling of the skin of the posterolateral thigh when the subject stood with the affected leg flexed to 90 degrees at the hip and knee. Any continuous area of skin at least 3 cm in diameter in which no dimpling was evident was designated as "unaffected." In all affected individuals, studies were performed to include both affected and unaffected areas of the thigh. In vitro pathologic examination of wedge biopsies and in vivo sonographic examination of the thigh both showed a diffuse pattern of extrusion of underlying adipose tissue into the reticular dermis in affected, but not unaffected, individuals. In vitro and in vivo studies also demonstrated that women had a diffuse pattern of irregular and discontinuous connective tissue immediately below the dermis, but this same layer of connective tissue was smooth and continuous in men. This connective tissue layer was more irregular and discontinuous in affected versus unaffected individuals. No significant differences were noted in subcutaneous adipose tissue morphology, lipolytic responsiveness, or regional blood flow between affected and unaffected sites within individuals. There is a sexual dimorphism in the structural characteristics of subdermal connective tissue that predisposes women to develop the irregular extrusion of adipose tissue into the dermis, which characterizes cellulite. These gender-related differences are diffuse and not localized only to affected areas. There is no evidence of any primary role for adipose tissue physiology, blood flow, or biochemistry in the etiology of cellulite, although the connective tissue of the female thigh is structured to accentuate differences in small subdermal adipose tissue depots.
Abdomen↗
Dan Waldorf: the scientist and the man.
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Crime↗
The physiology of body weight regulation: relevance to the etiology of obesity in children.
The prevalence of obesity in children and adults in the United States has increased by more than 30% over the past decade. Recent studies of the physiology and molecular genetics of obesity in humans have provided evidence that body weight (fat) is regulated. Some of the genes encoding the molecular components of this regulatory system have been isolated from rodents. The increasing prevalence of obesity in the United States apparently represents the interaction of these genes with an environment that encourages a sedentary lifestyle and consumption of calories. The rapid increase in the prevalence of obesity emphasizes the role of environmental factors, because genetic changes could not occur at this rate. Thus, understanding of the relevant genes and how their effects are mediated by environment and development should lead to more effective prophylaxis and therapy of obesity. Although no clear environmental factors have been identified as causative of obesity, the rapid increases in the prevalence of obesity and the seeming voluntary immutability of adult body fatness can be taken as tacit evidence that the pediatric environment can be altered in a way that affects adult body weight.
Adipose Tissue↗
Predischarge arrhythmia induction testing of implantable defibrillators may be unnecessary in selected cases.
Complete postoperative evaluation of implantable cardioverter-defibrillators (ICDs) before discharge, including arrhythmia induction, has been the standard since their introduction. Whereas the original ICDs provided little telemetered information and used separate pace-sense and defibrillation leads, modern, third-generation devices provide pace-sense function information in addition to other data and are used in conjunction with integrated transvenous endocardial leads that combine pace-sense and defibrillation function. Changes in lead position, which can potentially result in either an inability to detect fibrillation or to terminate it, should be mirrored by changes in resting pace-sense function. Thus, for newer ICDs implanted with integrated endocardial lead systems, it is possible that in at least some cases predischarge arrhythmia inductions can be avoided. Two hundred patients receiving third-generation ICDs in conjunction with integrated transvenous leads were evaluated before discharge. Defibrillation detection or termination problems were seen in 8. Declines in resting R-wave amplitude and pacing impedance were significantly associated with such complications (-7 +/- 5 vs -0.3 +/- 2.3 mV [p <0.0001] and -158 +/- 138 vs -93 +/- 76 omega [p <0.05], for those with vs without complications, respectively), as were gross right ventricular lead migrations on chest x-ray. No patient with a defibrillation complication had an R-wave change of <3 mV. However, 13% of patients without complications had R-wave changes of >3 mV. It is concluded that a pace-sense evaluation of ICDs may be a satisfactory screen to determine those who need to go on to complete testing with arrhythmia induction in selected cases.
Aged↗
Safety of slow pathway ablation in patients with atrioventricular node reentrant tachycardia and a long fast pathway effective refractory period.
Radiofrequency catheter ablation is an accepted primary therapy for atrioventricular (AV) node reentrant tachycardia (AVNRT). There is concern that slow pathway ablation in patients with a long anterograde fast pathway effective refractory period (ERP) may potentially impair subsequent node conduction. Eighteen patients (14 women; age 53 +/- 20 years) with symptomatic AVNRT, whose fast pathway ERP at baseline was > or = 500 ms, underwent slow pathway ablation. Their outcome was compared with 24 consecutive control patients (17 women; age 42 +/- 17 years) who underwent ablation for AVNRT whose fast pathway ERP at baseline was <500 ms (controls). Slow pathway ablation was successful in 16 patients (90%). One patient had inadvertent fast pathway ablation. In a second patient the slow pathway could not be ablated because of recurrent transient AV block. Ablation was successful in all patients in the control group. Transient AV block related to current application occurred in 4 patients (22%) versus 1 control (4%) (p = 0.07). After ablation, the AV node refractory period increased in patients (368 +/- 68 to 428 +/- 92 ms, p = 0.02) and in controls (282 +/- 35 to 336 +/- 55 ms, p <0.0001), but the fast pathway ERP shortened in both groups (patients: 558 +/- 63 to 428 +/- 92 ms, p = 0.003; controls: 356 +/- 53 to 336 +/- 55 ms, p = 0.05). Furthermore, the slope of the regression line relating to shortening of the fast pathway ERP to the baseline ERP was markedly steeper in patients compared with controls (1.9 vs 0.4, p <0.0001). The shortening of the fast pathway ERP was greater in patients compared with controls (122 +/- 130 vs 21 +/- 50 ms, p = 0.001). During a mean follow-up of 18 +/- 11 months, 1 patient with severe coronary artery disease died suddenly 2 years after ablation. There was no recurrence of clinical tachycardia, and none of the patients developed symptoms of bradycardia or required permanent pacing. Thus, slow pathway ablation in patients with AVNRT and a long fast pathway ERP is safe and effective.
Adult↗
Cardiac autonomic nervous system activity in obese and never-obese young men.
Autonomic nervous system (ANS) activity in age-matched, weight-stable, free-living, ad libitum-fed, obese (OB) and never-obese (NO) young men (body mass index means [SD], 38.5 [3.9] and 22.0 [1.7], respectively) was evaluated by sequential blockade of cardiac autonomic innervation with weight-adjusted doses of parasympathetic (atropine) and sympathetic (esmolol) blockers so as to produce maximal effects on heart rate. Change in heart period (interbeat interval) from baseline, induced by atropine, defined parasympathetic control (PC), and the subsequent change, after esmolol administration, defined sympathetic control (SC). The heart period, after PC and SC blockade, defined intrinsic heart period (I). In the OB group, baseline heart period and PC were lower, and SC and I were higher, than in the NO group. The results in the OB, relative to the NO subjects, are similar to those reported in a previous study of NO subjects who had undergone a 10% weight gain by overfeeding. These findings suggest that the ANS of individuals with obesity is chronically altered in a way that would tend to oppose their excessive adiposity, and that these autonomic changes are more likely to be responses to other forces that induce obesity, rather than being primary agents in the production of the disease.
Adult↗
A comparison of specialty choices, residency training, and practice locations of early-decision and regular-admission graduates.
PURPOSE: Early-decision (ED) medical school applicants express a clear preference for attending a particular medical school. The present study assessed whether ED graduates would demonstrate similar geographic preferences in their choices of undergraduate institutions and selections of in-state residency sites and practice locations. METHOD: The study was conducted at the University of Kentucky College of Medicine. Uniform academic and nonacademic criteria were used to evaluate the applications of ED and regular-admission students who matriculated from 1974-75 to 1984-85. The student variables assessed were class year, gender, age, county of residence, and undergraduate college, as well as undergraduate science and cumulative grade-point averages (GPAs) and Medical College Admission Test (MCAT) scores. Specialty choice and locations of residency programs were obtained from the medical school's commencement programs. Specialty types and practice locations were obtained from practicing physician records maintained by the alumni office. RESULTS: Of the 1,243 matriculants, 193 (15.5%) gained admission to the school through the ED plan. The ED graduates were significantly more likely to have completed their undergraduate studies at the University of Kentucky than at other public or private schools, in state or out of state, and had significantly higher GPAs and MCAT scores. As a group, the ED graduates were somewhat (though not significantly) more likely than the regular-admission graduates to remain in state for their residencies and practice in state. CONCLUSION: The authors suggest that medical schools should work closely with their undergraduate admission offices to attract academically outstanding high school students. Such students are likely to stay in state for the eight-year span of their undergraduate and medical educations and may have a greater tendency to practice in state.
Academic Medical Centers↗
Parents' and children's appraisals of each other's anxiety while facing a common threat.
The ability of 11-to 12-year-old children and their parents to infer each other's anxiety level under the threat of missile attacks during the 1991 Gulf War in Israel was investigated. An information exchange model for appraising other people's emotions served as the basis for predicting agreement rates among family members. As predicted, children's ratings of parental anxiety were primarily associated with their own anxiety (projected information), whereas parents' ratings of their spouses' and their children's anxiety were primarily predicted from spouses' self-reported anxiety (target-emitted information) and spouses' evaluations of the children's anxiety (shared information), respectively. Mother-father concordance on ratings of each other's and children's anxiety was significantly higher than parent-child agreement on parental and child anxiety. Agreement on parental anxiety among the 3 sources was partially a function of physical closeness among informants. The results suggest that at least within the nuclear family, under an external threat inferences about each other's anxiety level are partly based on social exchange of emotionally relevant information. However, it remains for future research to determine how exactly emotionally relevant information is communicated and processed.
Adult↗
Effects of weight change on plasma leptin concentrations and energy expenditure.
Circulating concentrations of leptin are closely correlated with body fat mass, and may thus constitute an afferent limb of a system regulating body fatness, with efferent limbs that affect energy expenditure and food intake. We studied 50 subjects (27 males, 23 premenopausal females; 31 never-obese, 19 obese) at usual body weight during active weight loss or weight gain and during the maintenance of body weights 10% above usual (WT + 10%) and 10% and/or 20% below usual body weight (Wt -10% and Wt -20%) to test the hypotheses that the dynamic process of weight change and the maintenance of an altered body weight are associated with significant changes in circulating concentrations of leptin and/or the relationship between fat mass and leptin, and such changes in the plasma concentration of leptin are related to changes in energy expenditure at altered body weight. Subjects were admitted to the Rockefeller University Hospital, and energy metabolism (24-h energy expenditure, resting energy expenditure, thermic effect of feeding, and nonresting energy expenditure) and circulating concentrations of leptin and insulin were examined at various weight plateaus (usual body weight, 10% above usual body weight, 10% below usual body weight, and 20% below usual body weight). Plasma leptin was also measured in some subjects during dynamic periods of weight gain or loss. Though both plasma leptin concentrations and fat mass were significantly correlated with resting energy expenditure, only the correlation of fat mass and energy expenditure remained significant in a multiple stepwise linear regression analysis. Neither absolute nor relative changes in plasma leptin between weight plateaus were significantly correlated with any of the observed changes in energy expenditure. Plasma leptin concentrations were significantly lower during weight loss than during weight maintenance at the same body composition. Plasma leptin concentrations, normalized to fat mass, were significantly lower during the maintenance of a reduced body weight in females and higher during the maintenance of an elevated body weight in males than in the same subjects at usual body weight. At all weight plateaus, plasma leptin concentrations normalized to fat mass were significantly higher in females than in males, but gender was not a significant covariate of the relationship between leptin and energy expenditure. Postabsorptive serum concentrations of insulin was a significant covariate of plasma leptin concentration in males, but not females, at Wt initial and Wt + 10%. Although plasma leptin is significantly reduced during dynamic weight loss compared with static weight maintenance at the same body weight, the lack of correlation between changes in plasma leptin and changes in energy expenditure between weight plateaus suggests that leptin is not the primary signal that mediates the changes of energy expenditure that accompany the maintenance of an altered body weight in humans.
Body Composition↗
Utility of full electrophysiological study before accessory pathway ablation in Wolff-Parkinson-White syndrome.
BACKGROUND: A single catheter technique has been described for ablation in patients with Wolff-Parkinson-White syndrome. It is unknown how often omission of a standard electrophysiological study would lead to misdiagnosis based on an assumption that the manifest accessory pathway is responsible for clinical tachycardia. OBJECTIVES: To examine the contribution of the standard electrophysiological study versus an abbreviated, single catheter approach in patients with Wolff-Parkinson-White syndrome and an overt delta wave electrocardiographically. PATIENTS AND METHODS: One hundred and fifty consecutive patients with a delta wave present on electrocardiogram referred for ablation had prior full diagnostic electrophysiological study. RESULTS: In 83% (124 of 150) of patients, the index accessory pathway was responsible for tachycardia and single catheter ablation would suffice. In 11% (17 of 150) of patients, the index pathway was not found to be the culprit producing tachycardia and in another 6% (nine of 150) additional information was obtained from electrophysiological study with possible clinical significance. CONCLUSIONS: Omission of the full diagnostic electrophysiological study is acceptable in the majority of patients presenting with a delta wave on electrocardiogram. However, important clinical information is missed in a sizeable minority of patients.
Adolescent↗
Semi-implantable middle ear electromagnetic hearing device for sensorineural hearing loss.
A semi-implantable middle ear electromagnetic hearing device (SIMEHD) is proposed for limited clinical trial in adult patients to evaluate the implantable hearing device for moderate to severe sensorineural hearing loss. Food and Drug Administration (FDA) investigational device exemption (IDE) approval has been granted (May 1996) for clinical trials. The implant unit has been evaluated acutely and chronically in animals (cats) with excellent results. Five cats undergoing chronic implantation were allowed to survive an average of 9.6 months, showing that the SIMEHD is biocompatible, functional and without untoward complications. All implant units recovered from the cats were functional, except for wire breakage of the internal antenna. A new antenna was redesigned for human implantation. The SIMEHD system consists of an external and internal unit. The external unit consists of a microphone, audio amplifier, modulator, radio frequency (RF) amplifier, antenna and battery. The internal unit is composed of a receiving antenna, hybrid electronic circuit, air core driving coil, and a target magnet cemented to the incus. All materials in contact with the body are biocompatible and expected to survive indefinitely. The implant unit is miniaturized and manufactured with existing fabrication technology by our industrial collaborator, Wilson Greatbatch, Ltd. The specific aims and major tasks of the proposed research are: a) to evaluate reliability, safety and efficacy of the SIMEHD system in a selected group of patients diagnosed with sensorineural hearing loss, due mainly to presbycusis or aging of the inner ear; and b) to obtain objective and subjective evaluation of audiologic and psychoacoustic performance as compared to the acoustic hearing aid. This paper describes the design, illustrates the actual device (newest prototype) and details the technique for surgical implantation in the attic and mastoid antrum in humans.
Adult↗
Understanding obesity in youth. A statement for healthcare professionals from the Committee on Atherosclerosis and Hypertension in the Young of the Council on Cardiovascular Disease in the Young and the Nutrition Committee, American Heart Association. Writing Group.
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Adolescent↗
Structural and functional analysis of the B cell epitopes recognized by anti-receptor autoantibodies in patients with Chagas' disease.
IgG fractions of patients were screened for autoantibodies against the beta1- and beta2-adrenoceptors and the M2 acetylcholine receptor by enzyme immunoassays and surface plasmon resonance (SPR) using peptides corresponding to the second extracellular loop of these receptors. A high prevalence of anti-M2 acetylcholine receptor and, in decreasing order, of anti-beta1- and anti-beta2-adrenoceptor autoantibodies was shown. The enzyme immunoassays and the SPR studies on the anti-beta1 adrenoceptor and the M2 acetylcholine receptor autoantibodies were dependent on the ionic strength of the interaction buffer, suggesting the importance of electrostatic interactions in Ab recognition. IgG fractions showed chronotropic effects on neonatal rat cardiomyocytes in vitro. The positive chronotropic effect was enhanced in the presence of 1 microM of atropine, demonstrating a muscarinic stimulation by the IgG fractions in the presence of a beta-adrenergic stimulation, which was blocked by the use of 1 microM of the beta1-selective antagonist bisoprolol. The beta2-selective antagonist ICI 118,551 only partially inhibited the positive chronotropic effect induced by the IgG fractions, confirming the minor functional importance of autoantibodies against the beta2-adrenoceptor. Affinity-purified Abs confirmed that Abs against the beta1-adrenoceptors and the M2 muscarinic receptors exist together with an Ab population recognizing a cross-reactive epitope on both receptors. This epitope could be identified as a polyanionic stretch present in the second extracellular loop of both the beta1-adrenoceptor and the M2 acetylcholine receptor. This stretch corresponds to the previously determined cross-reactive epitope between the P0 ribosomal protein of Trypanosoma cruzi and the beta1-adrenoceptor.
Adrenergic beta-Antagonists↗
Human eating: evidence for a physiological basis using a modified paradigm.
The aim of these studies was to determine if meal requests and changes in hunger ratings in humans were related to spontaneous changes in blood glucose concentration. In our first study, 18 healthy subjects were acutely isolated from food ant time cues. Blood glucose was continuously monitored online and visual analog ratings of hunger were obtained following an overnight fast. Spoken meal requests, if they occurred, were also recorded. In 83% of the subjects, both the perception and behavioral expression of hunger, as assessed by changes in hunger ratings and meal requests, were preceded by, and correlated with, brief, transient declines in blood glucose (nadir: -10% at 27 min). The pattern, magnitude and time course of these declines was similar to those observed in rats. This significant association, between increased expression of hunger and declines in blood glucose, is being tested in a second, ongoing study using acute insulin infusions to mimic spontaneous transient declines in blood glucose. Each subject was studied twice: either insulin or saline was infused while hunger ratings were obtained. Preliminary results in five subjects indicate that hunger ratings increased after insulin-induced transient declines in blood glucose. No change in hunger ratings occurred when blood glucose concentration was stable. These results suggest that this temporal pattern of blood glucose reflects an antecedent physiological event or provides a signal related to the expression of hunger in humans. Further understanding of human eating may result from investigation of the complex interaction of physiological and other factors in an experimental setting that allows the expression the behavior under study.
Adult↗
Distinguishing between state-dependent and non-state-dependent depression-related psychosocial variables.
The goals of this study were: (a) to determine which among a set of depression-related psychosocial variables are state-dependent; (b) to examine whether state-trait distinctions among psychosocial variables are a function of gender; and (c) to test the hypothesis that state-dependence of psychosocial variables is mostly evident in people with a history of clinical depression. Altogether, 562 participants residing in two communities completed a battery of psychosocial measures at point of entry into the study (T1) and after an average interval of 8.3 months (T2). The state-dependence of psychosocial variables was examined in two groups of participants: (a) low-high (LH: those who were low on the Center for Epidemiologic Studies Depression Scale at T1 and high at T2; N = 45); and (b) high-low (HL: those who were high at T1 and low at T2; N = 64). The following variables were found to be state-dependent: engagement in pleasant and unpleasant events; frequency of social contacts; dissatisfaction with oneself, one's neighborhood dwelling and one's friends; irrational beliefs, and positive and negative expectancies. In contrast, the following variables were not state-dependent: dissatisfaction with family and job, perception of control, and external attributions for positive and negative events. State-dependence was not moderated by age, gender or a history of depression. Possible explanations for why some variables are state-dependent and others are not state-dependent are offered.
Adult↗
A comparative study of different means of assessing long-term energy expenditure in humans.
We compared three independent techniques for measurement of total energy expenditure (TEE) in human subjects: 1) weight-maintaining energy intake (dietTEE), 2) 24-h chamber calorimetry (chamberTEE), and 3) differential elimination rates 2H2O and H(2)18O (isotopeTEE). Twenty-three healthy adult in-patients [19 never obese (NO), 2 obese (OB), and 2 formerly-obese (RO); 9 female, 14 malel] ingested a liquid formula diet (40% of calories as fat, 45% carbohydrate, 15% protein), the volume of which was adjusted until body weight was stable for at least 14 days. Body composition was then determined by hydrodensitometry, isotope dilution, and dual photon beam absorptiometry (DXA). The thermic effect of feeding (TEF) and resting energy expenditure [REE; measured before arising (dietREE) and after arising (chamberREE)] were determined by indirect calorimetry. Non-resting energy expenditure (NREE) was calculated as NREE = TEE - (REE + TEF). Subjects then gained or lost 10% of their body weight and were restudied as described above. All measures of TEE were significantly correlated (dietTEE vs. chamberTEE r2 = 0.75; dietTEE vs. isotopeTEE r2 = 0.88; isotopeTEE vs. chamberTEE r2 = 0.73; P < 0.0001). ChamberTEE (mean +/- SE = 2,107 +/- 64 kcal/day) was approximately 20% lower than either dietTEE (2,536 +/- 94 kcal/day, P < 0.0001) or isotopeTEE (2,564 +/- 83 kcal/day, P < 0.0001). When data were normalized to metabolic mass, weight gain of 10% was associated with significant increases in dietTEE (P < 0.005) and isotopeTEE (P < 0.05) but not chamberTEE; weight loss of 10% was associated with significant reductions in dietTEE (P < 0.005) and isotopeTEE (P < 0.05) but not chamberTEE. We conclude that measures of energy expenditure obtained in a highly controlled environment by caloric titration (dietTEE) or differential excretion rates of 2H2O and H(2)18O (isotopeTEE) are not significantly different and that measurements of TEE obtained in a respiratory chamber (chamberTEE) are significantly lower than dietTEE or isotopeTEE, probably largely due to limitations on physical activity in the chamber.
Adult↗