摘要:

Hypertension is a complex pathophysiological state that leads to serious complications, including heart failure, coronary artery disease, and abnormal renal function. While traditional therapies can be effective in controlling the effects of hypertension, they offer no long-term cure and often lead to patient noncompliance, thereby diminishing their effectiveness. These reasons, coupled with the recent developments in gene transfer and somatic cell gene delivery, led researchers to explore alternative options that can produce long-term control of hypertension. Gene therapy offers the potential to yield lasting antihypertensive effects by influencing the genes associated with hypertension. In this review, we will discuss the merits of sense versus antisense strategies in controlling hypertension. We also discuss the advantages and disadvantages of both viral and nonviral vector types for the systemic delivery of genes for hypertension research. Results of our research group on the retrovirus-mediated delivery of the angiotensin type I receptor-antisense on the prevention of hypertension and related cardiovascular pathophysiology will be summarized. Finally, we discuss the future of this gene therapy approach in the reversal and long-term control of hypertension.

ISSN:0002-9629    

出版商:OVID    

年代:2001

数据来源: OVID

摘要:

Vascular structure, function, and mechanics are altered in hypertension, which contributes to an important degree to complications of elevated blood pressure. Vascular hypertrophy with collagen deposition and increased stiffness is found in large arteries, whereas in small arteries, smooth muscle cells are restructured around a smaller lumen, and there is no net growth of the vascular wall, particularly in milder forms of hypertension. Hypertrophic remodeling and increased small artery stiffness may be found in more severe hypertension. Endothelial dysfunction occurs in large or smaller vessels in a variable percentage of patients, particularly in presence of other risk factors such as diabetes, smoking, dyslipidemia, and advanced atherosclerosis. In clinical trials, 1-year treatment with angiotensin-converting enzyme inhibitors, angiotensin AT1receptor antagonists, and long-acting calcium channel blockers corrected small artery structure and endothelial dysfunction in hypertensive patients, whereas &bgr;-adrenergic receptor blockers did not. Improved outcomes in hypertensive patients demonstrated in recent trials with some but not others of these agents could be a consequence, at least in part, of vascular protection offered by some antihypertensive agents.

ISSN:0002-9629    

出版商:OVID    

年代:2001

数据来源: OVID

摘要:

BackgroundThe occurrence of kidney stones is disproportionate in the southern region of the United States. Risk factors for the occurrence of kidney stones in this geographic area have not been reported previously.MethodsThe Women’s Health Initiative (WHI) is an ongoing multicenter clinical investigation of strategies for the prevention of common causes of morbidity and mortality among postmenopausal women. A case-control ancillary study was conducted on 27,410 (white or black) women enrolled in the 9 southern WHI clinical centers. There were 1,179 cases (4.3%) of kidney stones at the baseline evaluation. Risk factors for stone formation were assessed in cases versus age- and race-matched control subjects.ResultsMRisk factors (univariate) included low dietary potassium (2,404 versus 2,500 mg/day,P= 0.006), magnesium (243 versus 253 mg/day,P= 0.003) and oxalate (330 versus 345 mg/day,P= 0.02) intake, as well as increased body mass index (28.5 versus 27.7 kg/m2,P= 0.001) and a history of hypertension (42% versus 34%,P= 0.001). A slightly lower dietary calcium intake (683 versus 711 mg/day,P= 0.04) was noted in case subjects versus control subjects, but interpretation was confounded by the study of prevalent rather than incident cases. Supplemental calcium intake >500 mg/day was inversely associated with stone occurrence.ConclusionMultivariate risk factors for the occurrence of kidney stones in postmenopausal women include a history of hypertension, a low dietary intake of magnesium, and low use of calcium supplements.

ISSN:0002-9629    

出版商:OVID    

年代:2001

数据来源: OVID

摘要:

BackgroundPlasma plasminogen activator inhibitor-1 (PAI-1) is thought to contribute to the pathogenesis of atherosclerosis and is a predictor of ischemic heart disease.MethodsWe investigated the effects of overweight/obesity and lifestyle (smoking and alcohol intake) on plasma PAI-1 levels in 203 healthy men (age 44.5 ± 8.1) who visited our department for health check. Information on alcohol intake and smoking habit was obtained by a questionnaire.ResultsPlasma PAI-1 was significantly correlated to plasma leptin, body mass index (BMI), percent body fat, plasma levels of triglyceride, and &ggr;-glutamyl transpeptidase. Plasma PAI-1 was also increased significantly in smokers and in heavy drinkers. Plasma PAI-1 levels increased in an additive manner by the combination of risk factors (BMI ≥25 kg/m2, smoking, and heavy alcohol consumption). Nonobese, nonsmoking, nondrinkers showed the lowest plasma PAI-1 levels, whereas overweight/obese, smoking, heavy drinkers showed the highest levels (11.2 ± 2.2 ng/mL versus. 34.0 ± 4.3 ng/mL,P< 0.0001).ConclusionThese results suggest that overweight/obesity and unfavorable lifestyle such as smoking and heavy alcohol consumption may increase plasma PAI-1 levels and might be linked to the risk of ischemic heart disease.

ISSN:0002-9629    

出版商:OVID    

年代:2001

数据来源: OVID

摘要:

BackgroundEarly detection of cardiac autonomic neuropathy (CAN) permits individual risk stratification. Spontaneous heart rate variability (HRV) and baroreflex sensitivity (BRS) are suggested to be superior to classic autonomic testing in that they detect CAN earlier, with greater reliability, and do not require the patient’s undue attention.MethodsTo test that hypothesis, we studied 53 diabetic patients (mean age, 55 years) and 38 age-matched healthy control subjects (HC). Subjects underwent deep breathing, Valsalva maneuver, and orthostatic testing. Each abnormal test was counted as 1 point. A change in systolic blood pressure during standing of more than 10 mm Hg was graded with a single point; a decrease of more than 20 mm Hg received 2 points. A total score of zero was regarded as no CAN (noCAN), a score ≥4 as severe CAN (sCAN), and scores of 1 to 3 as mild CAN (mCAN). Spontaneous BRS was determined using the sequence technique. HRV was calculated as coefficient of variation (CV), high frequency power (HF) and low frequency power (LF).ResultsMean group values for HRV and BRS were: CV = 3.9 ± 1.3; 4.0 ± 1.3; 2.4 ± 1.1; and 1.2 ± 0.4; BRS = 8 ± 3; 8 ± 5; 5 ± 2; and 2 ± 2 msec/mm Hg for HC n = 38, noCAN n = 15, mCAN n = 26, and sCAN n = 12, respectively. BRS was similar in HC and patients with noCAN. In sCAN, BRS detected only 10 of 12 patients. HRV and BRS did not improve reclassification based on discriminant analysis.ConclusionBRS and HRV did not detect CAN in older diabetic patients better than classic autonomic testing.

ISSN:0002-9629    

出版商:OVID    

年代:2001

数据来源: OVID

摘要:

An impaired physician is one unable to fulfill professional or personal responsibilities because of psychiatric illness, alcoholism, or drug dependency. Current estimates are that approximately 15% of physicians will be impaired at some point in their careers. Although physicians may not have higher rates of impairment compared with other professionals, factors in their background, personality, and training may contribute and predispose them to drug abuse and mental illness, particularly depression. Many physicians possess a strong drive for achievement, exceptional conscientiousness, and an ability to deny personal problems. These attributes are advantageous for “success” in medicine; ironically, however, they may also predispose to impairment. Identifying impairment is often difficult because the manifestations are varied and physicians will typically suppress and deny any suggestion of a problem. Identification is essential because patient well-being may be at stake, and untreated impairment may result in loss of license, health problems, and even death. Fortunately, once identified and treated, physicians often do better in recovery than others and typically can return to a productive career and a satisfying personal and family life.

ISSN:0002-9629    

出版商:OVID    

年代:2001

数据来源: OVID

ISSN:0002-9629    

出版商:OVID    

年代:2001

数据来源: OVID

摘要:

We report a rare case of foreign body aspiration diagnosed by microscopic analysis of a sample of the foreign body. A 50-year-old man presented with a 5-month history of 40 pound weight loss and a nonresolving right lower lobe pneumonia. Medical history, radiographic studies, direct visualization of the foreign body by flexible fiberoptic bronchoscopy, and gross examination of a sample of the foreign body retrieved by a forceps biopsy catheter failed to yield the diagnosis. Moderate bleeding associated with the bronchoscopic “biopsy” procedure contributed to a preliminary misdiagnosis of endobronchial tumor. Microscopic analysis of the “biopsy” specimen demonstrated vegetable matter. The patient underwent rigid bronchoscopy and a peanut was retrieved from the bronchus intermedius. He was maintained on antibiotics for an additional 8 weeks and had complete clinical and radiographic recovery. The epidemiology, presentation, and management strategies of foreign body aspiration in the adult are briefly reviewed.

ISSN:0002-9629    

出版商:OVID    

年代:2001

数据来源: OVID

摘要:

Doxylamine succinate, an over-the-counter antihistamine, is commonly used as a nighttime sleep aid in the short-term management of insomnia. It is also used in combination with antitussive and decongestant agents for the temporary relief of common cold symptoms. Doxylamine is frequently involved in accidental and intentional overdoses. Rhabdomyolysis and secondary acute renal failure are rare but potentially serious complications, making early recognition and treatment essential. With the large number of nonprescription antihistamines and sleep aids available to the general public, it is important to keep in mind that overdose is a potential problem. The complications associated with overdose of these medications are just as life threatening as those associated with prescription drugs. A high index of suspicion and evaluation of rhabdomyolysis is warranted in antihistamine toxicity. We report an observation of severe rhabdomyolysis associated with doxylamine overdose.

ISSN:0002-9629    

出版商:OVID    

年代:2001

数据来源: OVID

摘要:

We report our experience with a 62-year-old Japanese man with cholesterol crystal embolism after angiographic procedures performed because of intermittent claudication. In addition to progressive renal failure and nephrotic-range proteinuria, cutaneous ischemia, consisting of livedo reticularis in the lower limbs and digital necrosis at the tip of the right toe, and fundoscopic findings showing several white spots in the branches of retinal artery were also observed. Progressive renal failure and nephrotic-range proteinuria were halted just after treatment with simvastatin. Thus, simvastatin can exert a beneficial therapeutic effect on renal cholesterol embolism.

ISSN:0002-9629    

出版商:OVID    

年代:2001

数据来源: OVID