Molecular basis and promise of genetic therapy for diabetic dyslipidaemia: studies in an animal model of diabetes.
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Biomedical subjects
Publications and source records attributed to L Chan.
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Treatment with beta-blockers has been reported to be associated with the development of hypertriglyceridemia. The etiology, even the existence, of this phenomenon is controversial. The purpose of our study was to examine whether the nonselective beta-blocker propranolol causes hypertriglyceridemia in the rat and whether its action is mediated by the modulation of lipoprotein lipase (LPL) messenger RNA (mRNA) accumulation or activity. LPL activity was assayed in fresh tissue by incubation with tritiated triglycerides. LPL mRNA was quantified in total RNA by slot-blot analysis using a mouse LPL complementary DNA probe. We have conducted three series of experiments in unanaesthetized rats in order to study the effects of different single doses of propranolol (1.5 to 6 mg i.p.) and different durations of treatment (15 min to 4 wk). We measured triglyceride and cholesterol levels in plasma as well as the LPL activity and mRNA levels in the heart and adipose tissue before and after propranolol administration. In these experiments we did not find any significant decrease in either the activity or the amount of mRNA of lipoprotein lipase nor was there any change in plasma lipids following treatment. Our results lead us to the conclusion that the nonselective beta-blocker propranolol affects neither the activity nor the mRNA level of LPL in the rat.
OBJECTIVE: To compare the total costs and the physician time requirements for suture and staple repair of pediatric scalp lacerations. STUDY DESIGN: Eighty-eight children, 13 months to 16 years of age, coming to a children's hospital emergency department with simple scalp lacerations were prospectively randomly selected to receive staple or suture repair. Wound lengths, times required for initial wound care and closure, and equipment use were recorded. Patients returned in 1 week for suture or staple removal and wound reevaluation. The two methods were compared in terms of both time expended and costs of equipment and physician compensation. RESULTS: Forty-five children underwent staple repair and 43 underwent suture repair. There were no differences in age, sex, wound length, number of sutures or staples per centimeter, or physician experience. Stapling resulted in shorter wound closure times (65 vs 397 seconds; p < 0.0001) and shorter overall times for wound care and closure (395 vs 752 seconds; p < 0.0001). Staple repair was less expensive in terms of equipment ($12.55 vs $17.59; p < 0.0001) and total cost based on equipment and physician time ($23.55 vs $38.51; p < 0.0001). The follow-up rate was 91%, with no cosmetic or infectious complications in either group. CONCLUSIONS: Stapling is faster and less expensive than suturing in the repair of uncomplicated pediatric scalp lacerations, with no additional complications. Physicians who treat children with scalp lacerations should consider the use of stapling devices.
This study compared the complication rates of tube thoracostomy performed in the emergency department (ED) versus the operating room (OR) and the inpatient ward (IW). A retrospective case series of all patients at an urban, university-based level 1 trauma center hospital who received tube thoracostomy for any indication between 1/1/93 and 12/31/93 was conducted. Complications were defined as empyema, unresolved pneumothorax (persistent air leak or residual pneumothorax), persistent effusion, or incorrect placement. The data for age and duration of tube placement were weighted for analysis of variance (ANOVA). A total of 352 tube thoracostomies was placed in 239 patients. Twenty-three patients had three or more chest tubes placed, 65 had two placed, and the remaining 181 had a single tube. Ninety-nine tubes were placed in the ED, 87 in the OR, and 166 on IW. The mean age of patients in the ED was 37 years, and differed significantly (P < .015) from those in the OR (48 years) and the IW (44 years). The duration of tube placement was similar for all groups (mean = 6.5 days). The overall complication rates related to tube insertion were: ED, 14.0%; OR, 9.2%; IW, 25.3%. Significance was achieved when comparing complication rates between the ED and IW, with less complications in the ED (P = .0436). When comparing complication rates between the ED and OR, there was no significant difference (P = .3643). A power calculation indicated too small of a sample size to truly determine an insignificant difference between complication rates between the ED and OR. Placement of emergent thoracostomy tubes in the ED does not result in an increased complication rate as compared to placement in the IW.
Three-dimensional ultrasonography is a promising new method for the prenatal diagnosis of fetal malformations, which offers several potential advantages, including the reduction of scanning time and the ability to store images that can be reviewed and reconstructed at a later date. Three-dimensional ultrasonography, however, has many of the same limitations as the conventional two-dimensional version.
Impairment of cardiac contractile function is an important component of acetate associated hypotension during hemodialysis treatments. We examined the effect of acetate on cardiac energy metabolism using the isovolumic isolated perfused heart model. In this preparation, acetate (10 M) caused decreases in tissue ATP concentrations (12.3 +/- 0.8 vs. 15.6 +/- 1.0 micromol/g dry at 30 min, P < 0.05) as well as marked impairment of systolic function (dpdt = 863 +/- 135 vs. 1288 +/- 166 mm Hg/second at 30 min, P < 0.05). Although altering perfusate calcium concentrations (0.6, 1.2 and 2.4 mM) affected physiological responses to acetate (5 and 10 mM), the reductions in tissue ATP concentrations were similar. In isolated heart mitochondria, acetate (100 microM -10 mM) selectively impaired octanoate and palmityl carnitine supported State 3 respiration in a dose dependent fashion (P < 0.01), but did not affect respiration when succinate, pyruvate/malate or malate/glutamate was used as substrate. We suggest that high concentrations of acetate selectively impair fatty acid metabolism in heart issue. This in turn leads to decreases in ATP production and tissue ATP concentrations that ultimately result in impaired contractile function. As this occurs at relatively low concentrations of acetate, this finding may be relevant to other parenterally-administered acetate containing fluids.
Sonographic imaging of the fetal face is important because a number of chromosomal aberrations are associated with facial malformations. Prenatal diagnosis of abnormalities of the fetal chin and lips have been based on subjective assessment. The purpose of the current study was to establish normative dimensions for the objective assessment of the fetal face. A cross-sectional study was performed in 200 normal healthy singleton pregnancies between 16 and 38 weeks' gestation. Inclusion criteria included performance of a first or early second-trimester scan to confirm gestational age (GA). Exclusion criteria included birth weight < 10th or > 90th percentile for GA, and medical complications of pregnancy. Ultrasound measurements were made in the mid-sagittal plane and included chin length (CL) and upper lip width (ULW). A first-degree linear growth function was observed throughout pregnancy between GA and ULW (r = 0.87) and CL (r = 0.91). All measured data are expressed as mean +/- 2 SD. In conclusion, these results provide normative dimensions throughout gestation for the fetal upper lip and chin. These data are expected to serve as a basis for the objective assessment of the fetal face in high-risk conditions.
Pneumothorax is extremely rare during pregnancy. We describe two antepartum cases temporally associated with cocaine use with a review of the literature and discussion on treatment options. Case 1, a 39-year-old female, presented at 31.3 weeks' gestation with a right pneumothorax after smoking crack cocaine. The pneumothorax was refractory to conservative therapy necessitating transaxillary resection of apical lung blebs. Fetal compromise was diagnosed at 34.6 weeks of gestation requiring induction of labor and subsequent delivery of a viable infant. Case 2, a 27-year-old female, presented at 28.9 weeks of pregnancy with her third episode of recurrent left pneumothorax. Thoracotomy and excision of lung bleb was performed and the patient was discharged on postoperative Day 5. Although the patient denied any history of drug use, drug screens were positive for cocaine. The patient delivered at term without further complications. Cocaine use is a predisposing factor for pneumothorax during pregnancy. Spontaneous pneumothorax carries a high risk of recurrence, possibly higher if induced by continued cocaine-use. Surgical intervention should be considered in refractory or recurrent cases.
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Oxidative modification converts LDL to an atherogenic form and 15-lipoxygenase has been implicated in this process. Several lines of experimental evidence support such a proatherogenic action of the enzyme. However, recent data obtained with transgenic rabbits overexpressing 15-lipoxygenase suggest also an antiatherogenic effect. In this paper the pathophysiological relevance of 15-lipoxygenase in atherogenesis is critically reviewed.
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OBJECTIVE: To determine the significance of a low out-of-hospital systolic blood pressure (SBP) reading in blunt trauma patients who have a normal SBP upon ED arrival. METHODS: A retrospective case-control study compared admitted blunt trauma patients who were hypotensive (SBP < or = 90 mm Hg) in the field and normotensive in the ED (group 1) with those who were normotensive both in the field and in the ED (group 2). The groups were compared for mortality, intensive care unit (ICU) admission, injury severity scale (ISS) score, need for transfusion in the ED, incidence of intra-abdominal injury, and incidence of pelvic or femur fracture. RESULTS: Each group consisted of 52 patients. The groups were similar with respect to age, gender, and initial ED SBP. The group 1 patients had a higher mortality (10 vs 1, p = 0.008), a higher number of ICU admissions (28 vs 12, p = 0.001), more pelvic or femur fractures (16 vs 7, p = 0.03), and a higher ISS score (19.0 vs 10.5, p = 0.01). Although not significant, group 1 also had higher incidences of intra-abdominal injury (10 vs 3, p = 0.07) and transfusion (8 vs 2, p = 0.09). CONCLUSION: The injured patients who were hypotensive in the out-of-hospital setting but normotensive upon ED arrival were more severely injured and had more potential for blood loss than were the patients who were normotensive both in the out-of-hospital setting and in the ED. Out-of-hospital hypotension may be a clinical predictor of severe injury, even in the face of normal ED SBP. Prospective studies are indicated to validate this hypothesis.
Adenovirus-mediated gene delivery of apolipoprotein (apo)B mRNA editing enzyme (AvApobec1) was used to study the effect of apoB mRNA editing on apoB production in homozygous LDL receptor-deficient (LDLR-/-) mice. Intravenous injection of AvApobec1 into these mice resulted in a >80% decrease in plasma apoB-100 with a concomitant increase in plasma apoB-48 level. The plasma apoE level also increased. In all cases, total plasma apoB (apoB-100 + apoB-48) decreased by 60% at day 5 and remained approximately 40% lower in AvApobec1-treated compared with control vector Av1LacZ4-treated animals at day 12. On day 12, total plasma cholesterol decreased by 29% in male mice and 18% in female mice that were transduced with AvApobec1. This was reflected in a reduction in apoB-containing lipoprotein cholesterol, which decreased by 34% and 27% in male and female mice, respectively. Apobec1 gene transfer also decreased the cholesteryl ester contents in the LDL fraction, which were 16%, 22%, and 22% in female and 20%, 20%, and 15% in male animals on days 5, 7, and 12, respectively, compared with Av1LacZ controls with 29%, 32%, and 33%, respectively, in female and 29%, 38%, and 36%, respectively, in male animals. Nondenaturing gradient gel electrophoresis indicated almost complete elimination of LDL particles of 29, 27, and 25 nm at days 7 and 12. We conclude that in the absence of a functioning LDL receptor, hepatic overexpression of Apobec1 is highly efficient in lowering plasma apoB-100 levels, leading to the almost complete elimination of LDL particles and a reduction in LDL cholesterol and cholesteryl ester content.
One of the most important parameters that influence patient satisfaction with emergency department care is their perception of throughput time. It is defined in our department as the time from patient arrival to time of discharge. Measurement of throughput time is one objective measure of efficiency that is feasible in most emergency departments. The purpose of this study is to analyze the impact of certain demographic and resource utilization factors on patient throughput times. Analysis of variants through multiple regression was used to determine associations between the average daily throughput time and factors commonly assumed to have significant influence on patient throughput time. Our data analysis found that patient throughput was significantly affected by the number of inpatient admissions from the emergency department, daily census in the main emergency department, pediatric volume, and the number of ambulance arrivals. Several factors that were commonly assumed to affect patient throughput time, such as nursing hours worked and day of the week, were not significant.
Sonographic imaging of the fetal face is important since a number of chromosomal aberrations are associated with facial malformations. In the past, imaging of the fetal forehead and diagnosis of frontal bossing had been based on subjective evaluation using two-dimensional ultrasonography. The purpose of this study was to evaluate quantitatively the fetal forehead using three-dimensional technology to generate normative data throughout gestation. This should allow the objective diagnosis of abnormal growth of the fetal forehead, such as frontal bossing. We also report a case of a fetus with frontal bossing in whom the generated nomogram was applied. A cross-sectional study was performed in 130 normal healthy singleton pregnancies between 16 and 38 weeks' gestation. Using three-dimensional ultrasonography, a line connecting the apex of the philtrum and the nasion was drawn across the anterior forehead, which delineated the area of the forehead for analysis. The forehead length, forehead height, and forehead area under the curve were measured and the forehead index was calculated. A second order polynomial growth function was noted throughout gestation for the forehead length (r = 0.93), forehead height (r = 0.97), and forehead area (r = 0.97). The fetal forehead index remained relatively constant throughout gestation. The results of this study provide normative data of fetal forehead length, width, and area using three-dimensional ultrasonographic technology. Normative dimensions of the fetal forehead developed and presented herein are expected to serve as a basis for the objective assessment of presumed fetal facial abnormalities and may facilitate the detection of the associated syndromes. This is demonstrated in our case report of an achondroplastic fetus in whom all forehead dimensions were above the 95th percentile.
Primary care physicians may encounter patients with altered mental status or neurologic deficit. Because the differential diagnosis for altered mental status includes conditions with significant morbidity and mortality, care of these patients must be rapid and thorough. The resources required to ensure and maintain cardiopulmonary stabilization and to perform the initial workup are often unavailable in the primary care office setting. Therefore, these patients often require immediate referral to an emergency department. Proper evaluation and initial management include evaluation of metabolic factors, assessment for toxic ingestions and a thorough neurologic assessment.
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