Assessment of alleged rape victims.
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Female↗
Biomedical subjects
J Myers
Publications and source records attributed to J Myers.
Influence of the exercise protocol on hemodynamic, gas exchange, and neurohumoral responses to exercise in heart transplant recipients.
BACKGROUND: A gradual accommodation to increasing exercise loads has been recommended for exercise testing in denervated posttransplantation heart recipients. However, how the exercise protocol influence the hemodynamic, gas exchange, and hormonal response to exercise in this not been studied. METHODS: Nine heart transplant recipients tests incremental maximal bicycle ergometry tests in random order. Exercise stages of 1 and 3 minute durations were compared with matched work rate increments ranging between 30 and 40 W. Expiratory gas was measured continuously and arterial blood was sampled at each of the matched work rates. RESULTS: Total exercise duration was 6.4 +/- and 15.3 +/- 0.7 minutes for the 1-minute and 3-minute protocols, respectively. Maximal workload was significantly higher during the 1-minute versus the 3-minute protocol (238 +/- 9 versus 200 +/- 11 W, p < 0.001), but maximal oxygen uptake was not significantly different (25.5 +/- 1.1 versus 26.5 +/- 1.2 ml. min-1.kg-1). Hemodynamic, metabolic, and some hormonal parameters showed marked differences between the two protocols, with significantly higher responses observed during the 3-minute protocol for heart rate, ventilation, lactate, atrial natriuretic factor, and growth hormone. Catecholamine (epinephrine and norepinephrine) and insulin responses did not differ between the two tests. If expressed as a relative exercise intensity (percentage of maximal oxygen uptake) no differences in hormonal responses were observed between the two protocols, except for growth hormone response which remained higher during the 3-minute protocol. CONCLUSIONS: Although maximal oxygen uptake was independent of the exercise protocol in these heart transplant recipients, the exercise protocol has a major influence on the hormonal and metabolic response. The delayed response observed for oxygen uptake and hormonal responses suggests a significant physiologic lag time during the more rapidly incremental protocol. These differences should be taken into account when exercise is used as a method to evaluate the heart transplant recipient.
Adult↗
The oncology nursing image: lifting the mist.
PURPOSE/OBJECTIVES: To examine oncology nurses' perceptions of their professional image and describe implications and strategies for practice. DATA SOURCES: Individuals in 28 Oncology Nursing Society (ONS) image focus groups and 13 validation focus groups in local ONS chapters throughout the United States. DATA SYNTHESIS: Although they used both negative and positive descriptors, participants believed the primary perceptions of physicians, administrators, and other nurses regarding oncology nurses were negative, whereas the perceptions of patients and families generally were more positive. Participants believed a lack of understanding exists about oncology nurses, their duties, and the impact of their specialized skills and knowledge on patient-care outcomes. They also believed that the current image of oncology nursing was not one they desired. CONCLUSIONS: Oncology nurses were concerned about their image and believed their external publics (e.g., physicians, administrators, nononcology nurses, patients, families) did not have a clear picture of who they are and what they do. They felt this lack of understanding led to diminished relationships with colleagues and patients/families and a lack of recognition of the oncology nurse as a valued member of the healthcare team. Participants felt this image could be changed and identified strategies to achieve their desired image through activities related to research, education, professionalism, communication, and influence. IMPLICATIONS FOR NURSING PRACTICE: Understanding the possible barriers to collaborative relationships, cost-effective care, disparate feelings of colleagues and external publics, and negative stereotypes will foster strategies to enhance relationships and improve care.
Adult↗
Presence in human eosinophils of a lysophospholipase similar to that found in the pancreas.
The supernatant fraction from lysed human eosinophils, when separated by gel-filtration chromatography, contains a protein with lysophospholipase activity of approximate molecular mass 74 kDa. This mass differs substantially from the 17 kDa of a previously cloned eosinophil lysophospholipase (Charcot-Leyden crystal protein), but is similar to that reported for a pancreatic enzyme. We have therefore further characterized this pancreatic-like lysophospholipase in human eosinophils. A rabbit polyclonal antibody was produced against a synthetic peptide consisting of amino acids 325-349 from the 74 kDa rat pancreatic lysophospholipase. Western-blot analysis of eosinophil extracts indicate that this antibody recognizes a single 74 kDa band in these preparations. Incubation of the supernatant fraction from sonified eosinophils with this antibody, followed by precipitation of antibody-antigen complexes with Protein A, removes the majority of the lysophospholipase activity. Indirect immunofluorescence examination with this antibody indicates this protein to be localized to granules of eosinophils and not in other leucocytes. Moreover, reverse transcriptase PCR of polyadenylated RNA from eosinophils and from rat pancreatic tissue with primers to rat pancreatic lysophospholipase resulted in readily detectable 1 kb DNA products in both samples. Sequencing revealed this DNA fragment to be identical with the human pancreatic lysophospholipase cDNA sequence. Taken together, these data indicate that eosinophils contain a lysophospholipase that is similar to the human pancreatic enzyme.
Amino Acid Sequence↗
Guidelines for clinical exercise testing laboratories. A statement for healthcare professionals from the Committee on Exercise and Cardiac Rehabilitation, American Heart Association.
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Electrocardiography↗
The effect of beta-blockade therapy on the response to exercise training in postmyocardial infarction patients.
Cardiac rehabilitation after a myocardial infarction has been shown to improve exercise capacity. Beta blockade has been shown to be effective in treating angina and reducing mortality, but studies are controversial as to whether beta-blockade therapy attenuates the effects of training. We attempted to study the effects of beta blockade (metoprolol) on the response to training in patients enrolled in a cardiac rehabilitation program after an uncomplicated myocardial infarction. We studied 27 patients with a recent uncomplicated myocardial infarction who were subdivided in two groups: Group 1 (13 patients) not taking a beta blocker, and Group 2 (14 patients) taking metoprolol (mean 142 +/- 57 mg daily). All patients underwent a maximal cardiopulmonary exercise test before and after a 3-month training program. The training intensity was designed to approximate the ventilatory threshold. Results showed an increase in peak VO2 in both Group 1 (27%, p < 0.01) and Group 2 (33%, p < 0.001), and an increase in VO2 at the ventilatory threshold (39% in Group 1 and 28% in Group 2, p < 0.01). The mean changes in exercise capacity were not different between groups. It was concluded that metoprolol did not influence the beneficial effects of a cardiac rehabilitation program in postmyocardial infarction patients.
Adrenergic beta-Antagonists↗
Isolated metastasis to a pulmonary hamartoma.
Intrapulmonary hamartomas are the most common benign pulmonary neoplasm, and malignant degeneration is exceedingly rare. Only a minority produce symptoms, and their major clinical significance is their ability to simulate a malignant pulmonary neoplasm in radiologic studies. Here we report a case of apparently localized prostatic adenocarcinoma with isolated metastasis to an intrapulmonary hamartoma. The pulmonary lesion was identified during staging and was ultimately resected. Prostatic adenocarcinoma involved the hamartoma extensively but did not involve adjacent lung tissue. The hamartoma was otherwise typical with predominantly cartilaginous differentiation. The malignant glands within the hamartoma showed strong reactivity for prostate specific antigen, excluding the possibility of malignant change within the hamartoma. To our knowledge, metastasis to a pulmonary hamartoma has not been previously reported, and this case raises several issues. The pattern of tumor spread suggests an affinity of the tumor cells for the hamartoma. The known propensity of prostatic adenocarcinoma to metastasize to osseous sites might underlie its apparent tropism for the cartilaginous milieu of a pulmonary hamartoma. Accurate pathologic staging of this patient's prostatic adenocarcinoma prevented a needless radical prostatectomy, and complete cancer staging may require histologic examination of clinically typical pulmonary hamartomas.
Adenocarcinoma↗
Effects of posture on gastric emptying of nonnutrient liquids and antropyloroduodenal motility.
The effects of posture on gastric emptying, intragastric distribution, and antropyloroduodenal motility after ingestion of a nonnutrient liquid have been evaluated. In seven healthy volunteers antropyloroduodenal pressures were measured for 30 min after ingestion of 150 ml of normal saline in two different positions: sitting and left lateral. Saline drinks were radiolabeled and ingested both before and after intravenous atropine (4 micrograms/kg). Rates of emptying from both the total (P < 0.05) and the proximal (P < 0.05) stomach were faster in the sitting position than in the left lateral position. There were more long (> 6 cm) antropyloric pressure waves (P < 0.05) and isolated pyloric pressure waves (P < 0.05) in the sitting position. Intravenous atropine slowed emptying in both positions (P < 0.05) and in the sitting position decreased (P < 0.05) the number of antropyloric pressure waves. After atropine, gastric emptying was also faster in the sitting compared with the decubitus position (P < 0.05), although there was no difference in antropyloric or isolated pyloric pressure waves between the two postures. We conclude that the effects of gravity on gastric emptying of nonnutrient liquids are likely to reflect changes in both antropyloric motility and intragastric distribution.
Adolescent↗
Exercise capacity and prognosis in patients with chronic atrial fibrillation.
To evaluate the response of patients with chronic atrial fibrillation (AF) to exercise and to demonstrate if prognosis could be predicted, 200 male patients (64 +/- 1 years) with AF were identified retrospectively who underwent resting echocardiography and symptom-limited treadmill testing. They were classified by underlying disease into three subgroups: hypertension or no underlying disease (LONE; n = 102), ischemic heart disease (IHD; n = 45) and history of congestive heart failure or valvular disease (CHF-VD; n = 53). Maximal exercise capacities for LONE, IHD and CHF-VD were (mean +/- 1 SEM) 8.0 +/- 0.3, 6.4 +/- 0.4 and 6.0 +/- 0.3 metabolic equivalents, respectively (p < 0.01), and resting left ventricular ejection fractions were 61.7 +/- 1.6, 60.1 +/- 2.2 and 49.5 +/- 1.9%, respectively (p < 0.01). Stepwise multiple regression analysis demonstrated that, except for group classification (R2 = 0.13, p < 0.01), no clinical, exercise or morphologic variables could predict exercise capacity. After a mean 39.1-month follow-up (range 1-78), 17 of the 200 had died from cardiovascular causes. The rate of cardiac death using Kaplan-Meier survival analysis was significantly greater in CHF-VD patients (p < 0.01). However, Cox hazard function and Kaplan-Meier survival analysis demonstrated that neither echocardiographic measurements of cardiac size or function at rest, nor exercise or clinical variables were significant predictors of outcome. AF patients with a history of CHF and/or VD demonstrated a reduced exercise tolerance ad a worse prognosis than those without morphologic heart disease or those with IHD.(ABSTRACT TRUNCATED AT 250 WORDS)
Adult↗
Relationship of left ventricular structure to maximal heart rate during exercise.
Previous investigators using clinical, hemodynamic, or exercise parameters to predict maximal exercise heart rate (HRmax) have demonstrated age to be the major determinant. Regression coefficients have ranged from -0.3 to -0.6, leaving approximately two thirds of the variance in HRmax unexplained. Because cardiac size and function are directly related to stroke volume and should influence HRmax, we studied 114 male subjects (aged 19 to 73 years) with two-dimensional and M-mode echocardiography who underwent maximal treadmill testing with respiratory gas analysis. Seventy-three were normotensive (diastolic BP < 95 mm Hg) and 41 were hypertensive. As in previous studies, HRmax was inversely related to age (HRmax = 199-0.63[age], r = -0.47, p < 0.001). M-mode left ventricular (LV) diastolic dimension (LVD) added significantly to the explanation of the variance in HRmax (r = -0.57, p < 0.001) (HRmax = 236 - 0.72 [age]-6.8 [LVD]). Thus, the larger the heart, the lower the HRmax. No other echocardiographic measurement or derived parameter added significantly to the explanation of the variance in HRmax. To evaluate the effects of hypertension on HRmax, we studied hypertensives and normotensives separately. Only age was significantly related to HRmax in the normotensives (r = -0.50, p < 0.001). In the hypertensive subjects, however, both age and relative wall thickness (RWT) (which describes LV wall thickness in relation to LV chamber size) were significantly related to HRmax. Age explained 45% of the observed variance in HRmax (r = 0.67, p < 0.001) and RWT added modestly (9%) but significantly to the relationship (HRmax = 173-0.96[age]+94 [RWT], p < 0.001), together explaining 54% of the variance observed in HRmax. Thus, HRmax is inversely related to LVD and patients with larger ventricles achieve lower HRmax. In hypertensives, the amount of LV muscle mass in relation to chamber size is an additional predictor of HRmax. However, despite controlling for age, sex, and cardiovascular disease, and the inclusion of echocardiographic indices of cardiac size and function, a large portion of the variance in HRmax could not be explained. The unexplained variance in HRmax is most likely due to intersubject variability in resting cardiac size, volume, function, and other as yet undefined factors.
Adult↗
Effect of residential cardiac rehabilitation following bypass surgery. Observations in Switzerland.
BACKGROUND: Cardiac rehabilitation in central Europe traditionally involves isolating patients in a residential idyllic setting where exercise is performed frequently but in a relatively unstructured fashion. Few studies have been performed on the effects of these programs among patients who have undergone bypass surgery. Recent data suggest that postbypass patients may enter these programs too soon after surgery or that exercise is not structured enough to distinguish the benefits of rehabilitation from those experienced by a control group. METHODS: Forty-two male patients (mean age, 58 +/- 7 years) were divided into exercise and control groups approximately 1 month after undergoing bypass surgery. Exercise training consisted of 1 h of group walking twice daily, with the intensity stratified into four levels based on initial exercise capacity. Using a crossover design, patients in the exercise group participated in rehabilitation for 1 month, followed by 1 month of usual care, while control patients underwent the opposite sequence. At 1, 2, and 3 months, patients in both groups underwent pulmonary function testing and maximal ramp exercise testing using lactate and gas exchange analysis. RESULTS: A main effect for maximal oxygen uptake was observed; significant improvements within each group occurred across each testing period (range, 5 to 13%; p < 0.05). However, there was no significant interaction between groups. Mean lactate levels throughout exercise were reduced within both groups (p < 0.01). A reduction in oxygen uptake for test 2 at the lactate threshold in the exercise group resulted in differences between groups in lactate, heart rate, and other gas exchange variables at this point. CONCLUSION: Similar changes occur in the functional status of postbypass surgery patients regardless of their participation in the short but concentrated programs common in central Europe. This suggests that a significant spontaneous effect of healing occurs in the recovery phase after surgery. These programs may have greater efficacy if they began later after surgery, lasted longer, or were more structured, and studies are needed to determine their effect on psychosocial factors and return to work.
Aged↗
Pharmacological properties of recombinant human N-methyl-D-aspartate receptors comprising NR1a/NR2A and NR1a/NR2B subunit assemblies expressed in permanently transfected mouse fibroblast cells.
The pharmacological properties of two recombinant human N-methyl-D-aspartate (NMDA) receptor subtypes, comprising either NR1a/NR2A or NR1a/NR2B subunits permanently transfected into mouse L(tk-) cells, have been compared using whole-cell voltage-clamp electrophysiology. Glutamate was a full agonist at both receptors, having a modestly but statistically significant (p < 0.002) higher affinity for the NR2B- than the NR2A-containing receptor (microscopic Kd [mKd] = 0.76 and 0.43 microM, respectively). In comparison to glutamate, NMDA, quinolinic acid, and cis-2,3-piperidinedicarboxylic acid were partial agonists at both receptor subtypes. Maximal amplitude currents resulted when glutamate-site agonists were combined with either glycine or D-serine; both of these amino acids were, therefore, defined as full agonists at the glycine site. Glycine had an approximately 10-fold higher affinity (p < 0.0001) for NR2B- than for NR2A-containing receptors (mKd = 0.057 and 0.53 microM, respectively). D-Cycloserine, (+)-(3R)-3-amino-1-hydroxypyrrolidin-2-one, (+)-cis-(4R)-methyl-(3R)-amino-1-hydroxypyrrolidin-2-one, and 1-aminocyclobutanecarboxylic acid also had higher affinities for the NR2B-containing receptor but were partial agonists, at both receptor subtypes, unlike glycine. Agonist-evoked whole-cell currents were antagonized by D-(-)-2-amino-5-phosphonopentanoic acid, cis-4-(phosphonomethyl)piperidine-2-carboxylic acid, and 3-((R)-2-carboxypiperazin-4-yl)-propyl-1-phosphonic acid, all of which had slightly, but statistically significant, higher affinities (2.2-, 2.8-, and 5.5-fold, respectively) for the NR2A-containing receptor. Responses were also antagonized by the glycine-site antagonists 7-chlorokynurenic acid, 7-chloro-4-hydroxy-3-(3-phenoxy)phenylquinolin-2-(1H)-one, and (+/=)-4-(trans)-2-carboxy-5,7-dichloro-4-phenylaminocarbonylamino- 1,2,3,4- tetrahydroquinoline. The atypical NMDA antagonist ifenprodil showed the largest separation in functional affinity (IC50 values, 0.6 and 175 microM at NR2B- and NR2A-containing receptors, respectively). These experiments demonstrate the usefulness of permanently transfected L(tk-) cells for electrophysiological studies of recombinant NMDA receptor function and provide the first detailed functional pharmacological analysis of human NMDA receptor subtypes.
Animals↗
Steroid-sensitivity of agonist binding to pituitary cell line histamine H3 receptors.
Histamine H3 receptors have been identified in rat and guinea-pig pituitary glands and in the mouse pituitary tumor cell line, AtT-20. Histamine H3 receptor agonists are reported to stimulate adrenocorticotropic hormone (ACTH) release from AtT-20 cells, an effect blocked by histamine H3 but not H1 or H2 receptor antagonists. To determine whether negative feedback regulation of the histamine H3 receptor-mediated effect might occur, we tested the effects of steroid treatment upon binding of the agonist [3H]N alpha-methylhistamine to AtT-20 cell membranes. Consistent with feedback regulation, steroid treatment of the cells reduced [3H]N alpha-methylhistamine binding. The effect was dose-dependent and was greatest for glucocorticoids among the steroids tested. As the duration of steroid treatment increased, the amount of [3H]N alpha-methylhistamine binding decreased, to 15% of control at 36 h. However, the effect was not specific for histamine H3 receptors. Somatostatin inhibits ACTH release from these cells and its binding was similarly reduced by steroid treatment. Because steroids have been reported to modulate levels of guanine nucleotide-binding proteins, the lack of receptor specificity could reflect an indirect effect of steroids upon agonist binding and, in fact, we show that [3H]N alpha-methylhistamine binding to these cells, like somatostatin, is pertussis toxin-sensitive. However, steroid treatment does not alter the apparent levels of pertussis toxin substrate in these cells. Whether steroid treatment affects histamine H3 receptors of these cells directly or through some more subtle effect upon the guanine nucleotide-binding proteins to which they couple, the result is a negative feedback loop that attenuates [3H]N alpha-methylhistamine binding to these cells.
Adenosine Diphosphate↗
A nomogram to predict exercise capacity from a specific activity questionnaire and clinical data.
Recent investigations suggested that clinical exercise testing can be optimized by individualizing the protocol, depending on the purpose of the test and the subject tested. This requires some knowledge of a patient's exercise capacity before beginning the test. The accuracy of a simple physical activity questionnaire and readily available clinical data in predicting subsequent treadmill performance was examined. A brief, self-administered questionnaire (VSAQ) was developed for veterans who were referred to exercise testing for clinical reasons. The VSAQ was designed to determine which specific daily activities were associated with symptoms of cardiovascular disease (fatigue, chest pain and shortness of breath). Two hundred twelve consecutive patients (mean age 62 +/- 8 years) referred for maximal exercise testing were studied. Clinical and demographic variables were added to VSAQ responses in a stepwise regression model to determine their ability to predict treadmill performance. Only metabolic equivalents by VSAQ, and age were significant predictors of treadmill performance; these 2 variables yielded R = 0.82 (SEE 1.43; p < 0.001), and explained 67% of the variance in exercise capacity. The regression equation reflecting the relation between age, VSAQ and exercise capacity was: achieved metabolic equivalents = 4.7 + 0.97 (VSAQ) - 0.06 (age). Using this equation, a nomogram was developed. Incorporating the VSAQ with the nomogram requires only a few minutes, and yields a reasonably accurate estimate of a patient's exercise capacity. Although the present equation is population-specific, a similar approach in different populations may be useful for individualizing protocols for clinical exercise testing.
Activities of Daily Living↗
Influence of right coronary artery stenosis on exercise test responses and survival in patients with left main or left main equivalent disease.
Forty-two patients with angiographically documented left main coronary artery (LM) disease (luminal occlusion > or = 50%) and 30 patients with left main equivalent (LMEQ) disease (> or = 70% luminal occlusion of both the proximal left anterior descending artery and proximal left circumflex artery) were studied to determine the role of right coronary artery (RCA) involvement on exercise test responses and survival. Significant (> or = 70%) RCA stenosis was present in 30 (72%) of the 42 LM patients and 16 (53%) of the 30 LMEQ patients. No significant differences were observed between LM and LMEQ patients in any clinical or exercise variables or survival. Thus both groups were combined for analysis of the influence of RCA involvement (i.e., LM/LMEQ with RCA versus LM/LMEQ without RCA disease). Greater ischemic responses were observed in the LM/LMEQ group with significant stenosis of the RCA. The presence of RCA stenosis was associated with significantly greater horizontal or downsloping ST-segment depression during exercise (2.4 +/- 1.2 mm vs 1.3 +/- 1.4 mm; p < 0.001), and prolonged recovery time until normalization of the ST segment (3.2 +/- 1.4 min vs 2.0 +/- 1.9 min; p < 0.01). The LM/LMEQ without RCA disease group behaved like the subgroup with two-vessel disease, and responses of the LM/LMEQ group with RCA disease were similar to the group with three-vessel disease. The annual survival in LM/LMEQ with RCA disease was worse than that in LM/LMEQ without RCA disease (average annual mortality rates = 7.5% vs 1.0%, respectively; p = 0.05). Infarct-free survival in LM/LMEQ with RCA disease was also lower than that in LM/LMEQ without RCA disease. Thus although patients with LM and LMEQ were similar in terms of survival and exercise responses, the presence of RCA stenosis was associated with significantly greater ST-segment depression, a prolonged recovery time until normalization of the ST segment, a fivefold increase in the death rate, and higher morbidity from myocardial infarction over a 5-year period of follow-up. Involvement of the RCA should be considered when making decisions concerning medical-surgical management of patients with severe coronary artery disease.
Aged↗
Transfer as a component of the transition of adolescents with sickle cell disease to adult care: adolescent, adult, and parent perspectives.
PURPOSE: There are no empirical studies which access the transfer needs/concerns of adolescents and young adults with sickle cell disease (SCD) and their primary caretakers. The overall purpose of this research was to determine the issues, concerns, and expectations of adolescents, young adults and primary caretakers with regard to transfer to adult care. METHODS: Participants were recruited from clinics and programs participating in the Duke/UNC Comprehensive Sickle Cell Program. Using a cross-sectional survey design, young adults (n = 60), adolescents (n = 36) and primary caretakers (n = 25) were administered the Sickle Cell Transfer Questionnaire (SCTQ). RESULTS: Adolescents and young adults with SCD were primarily concerned about how they would pay for medical care and how they would be treated by adult providers. Caretakers were concerned about their teens leaving pediatric care and assuming responsibility for medical care. All three groups reported mixed emotions about leaving pediatric care. There was consensus among the respondents regarding the need for transfer programs and what they should offer. Bivariate analysis revealed that age, education level, and disease severity were statistically significant co-factors influencing the feelings, concerns and opinions of the study participants. CONCLUSION: Future longitudinal experimental research is needed to corroborate the results of this study and to assess the effectiveness of transition-related intervention programs for adolescents with SCD and their families.
Adolescent↗
Measurement of the ultrasonic attenuation of fat at high frequency.
RATIONALE AND OBJECTIVES: High-frequency ultrasound devices are often limited by a decreased depth of acoustic imaging caused by the increased attenuation of tissue at high frequencies. We investigated the role of adipose tissue in this phenomenon. METHODS: A substitution technique was used to calculate the ultrasonic attenuation (decibels per centimeter) of fresh samples of sheep rumen, omental fat, and back fat and swine back fat and various concentrations of bovine milk fat at 22 degrees C and 37 degrees C for frequencies of 15 and 20 MHz. RESULTS: The attenuation was significantly higher for sheep adipose tissue than for the intestinal wall, in descending order, omental fat, back fat, and rumen wall (P < 0.01). A correlation was found between bovine milk fat concentrations and attenuation at both frequencies (R2 > 0.9). The attenuation of adipose tissues decreased significantly with an increase in temperature (P < 0.01), whereas the attenuation of sheep rumen showed no significant change (P > 0.1). CONCLUSIONS: The ultrasonic attenuation of fat may contribute to limitations on the use of high-frequency ultrasound in clinical situations in which adipose tissue is present.
Adipose Tissue↗
The effect of growth hormone replacement on serum lipids, lipoproteins, apolipoproteins and cholesterol precursors in adult growth hormone deficient patients.
OBJECTIVE: Adult patients with growth hormone deficiency are thought to be at higher risk of mortality from cardiovascular disease. We therefore investigated the effect of recombinant human growth hormone (rhGH) replacement therapy on fasting serum concentrations of lipids, lipoproteins and cholesterol precursors in adult growth hormone deficient patients. DESIGN: Double-blind placebo controlled trial. Patients were randomly allocated to placebo or rhGH replacement therapy (0.018 U/kg/day for 1 month followed by 0.036 U/kg/day for 1 month). PATIENTS: Eighteen patients with severe growth hormone deficiency. MEASUREMENTS: Fasting lipid, lipoprotein and cholesterol precursors (lathosterol and mevalonic acid) were measured at baseline and after 2 months. RESULTS: In the rhGH treated group there was a significant fall in serum cholesterol (P < 0.01) (6.44 +/- 0.49 to 5.71 +/- 0.48 mmol/l), LDL cholesterol (P < 0.02) (4.29 +/- 0.49 to 3.62 +/- 0.44 mmol/l), LDL cholesterol/HDL cholesterol ratio (P < 0.02) (3.99 +/- 0.62 to 3.26 +/- 0.39), apolipoprotein B (P < 0.01 (1.30 +/- 0.11 to 1.15 +/- 0.11 g/l) and mevalonic acid (P < 0.05) (13.4 +/- 10.96 to 6.21 +/- 1.91 micrograms/l). There were no significant changes in triglycerides, HDL cholesterol, apolipoprotein A1, lipoprotein (a) or lathosterol concentrations. In the GH treated group the rise in serum insulin was inversely correlated with the fall in cholesterol (P < 0.05), LDL cholesterol (P < 0.01) and apolipoprotein B (P < 0.01). There were no significant changes in any of the measured variables in the placebo group. CONCLUSION: We conclude that GH may be involved in the regulation of lipid and lipoprotein metabolism and that rhGH replacement therapy of adult GHD patients is associated with beneficial changes in lipid and lipoprotein profiles. The reduction in mevalonic acid is consistent with up-regulation of hepatic LDL receptors caused by GH and this may explain the fall in LDL cholesterol and apolipoprotein B concentrations.
Adult↗