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Biomedical subjects

J Sowers

Publications and source records attributed to J Sowers.

At least 19 recordsLinked to original sources

Preserving renal function in adults with hypertension and diabetes: a consensus approach. National Kidney Foundation Hypertension and Diabetes Executive Committees Working Group.

Over 11 million Americans have both diabetes and hypertension-comorbid diseases that strongly predispose people to both renal as well as cardiovascular (CV) injury. Hypertension substantially contributes to CV morbidity and mortality in people with diabetes. Diabetes is the most common cause of end-stage renal disease in the United States. Furthermore, hypertension and diabetes are particularly prevalent in certain populations, such as African-Americans and Native Americans. Since the 1994 Working Group Report on Hypertension and Diabetes, a large body of clinical trial data has affirmed the original blood pressure goal of less than 130/85 mmHg recommended to preserve renal function and reduce CV events in people with hypertension and diabetes. Data that are more recent have emerged, however, to support an even lower diastolic blood pressure goal, ie, 80 mmHg, in order to optimally preserve renal function and reduce CV events in people with diabetic nephropathy. A review of clinical trials indicates that more than 65% of people with diabetes and hypertension will require two or more different antihypertensive medications to achieve the new suggested target blood pressure of 130/80 mmHg. The purpose of this report is to update the previous recommendations with a focus on level of blood pressure control, proteinuria reduction, and therapeutic approaches to achieve these goals. We provide an evidence-based approach, integrating data from the major clinical trials that were designed as randomized prospective, long-term studies that had as a primary endpoint either progression of diabetic nephropathy or reduction in CV events. This report also addresses socioeconomic and cultural barriers that hinder achievement of blood pressure goals. Lastly, the report discusses approaches to resolve cultural barriers, both physician- and patient-derived, that interfere with achievement of lower blood pressure goals.

Adult↗

Hypertension in patients with diabetes. Why is aggressive treatment essential?

Hypertension and diabetes are interrelated diseases. Alone, each condition is a risk factor for cardiovascular disease and, together, they strongly predispose to end-stage renal disease, coronary artery disease, and peripheral vascular and cerebrovascular disease. Pharmacologic treatment of hypertension can substantially reduce morbidity and mortality in diabetic patients with hypertension, but adequate control of blood pressure is seldom achieved in a clinical setting. More aggressive treatment is needed to improve the prognosis for this over-expanding patient population.

Antihypertensive Agents↗

Roundtable discussion: Part I--Epidemiologic, demographic, and treatment challenges in hypertension.

Hypertension is one of the most pervasive medical disorders in this country. As the nation's population ages, the number of patients with hypertension can be expected to rise substantially. On December 9, 1999, a panel of managed care medical directors, pharmacy directors, clinicians, and health economists convened in Irvine, Texas to discuss aspects of hypertension management and economic analysis. This roundtable is presented in three parts, including (1) a summary of the challenges of hypertension management from the point of view of the clinician, (2) the introduction of a pharmacoeconomic model of hypertension management, and (3) a discussion of how health plans approach this insidious disorder.

Aged↗

Roundtable discussion: Part II--Development of a pharmacoeconomic model in hypertension.

Antihypertensive medications are targeted by most health plans as a major cost center. However, the efficacy of these medications, their side effects, and their resulting ability to prevent serious long-term complications must be factored into the value equation. To illustrate the possible economic effects of a single antihypertensive agent's inclusion on a health plan's drug formulary, an innovative pharmacoeconomic model was developed. In this portion of the roundtable, the design, results, and caveats of this model are discussed.

Antihypertensive Agents↗

Roundtable discussion: Part III--Hypertension management in health plans.

In the final section of the roundtable discussion, participants describe how their individual managed care plans approach hypertension from the standpoints of disease management targeting, strategies to combat noncompliance, and how these plans utilize pharmacoeconomic information in drug formulary decision making.

Antihypertensive Agents↗

Central IGF-1 decreases systemic blood pressure and increases blood flow in selective vascular beds.

IGF-1 and its receptors have been identified in many tissues including the central nervous system (CNS). We have previously demonstrated that injection of insulin directly into the cerebral ventricles (ICV) is followed by a drop in mean arterial pressure (MAP) associated with an increase in skeletal muscle blood flow. Given the similarities between the IGF-1 and insulin molecules and their respective receptors, we have investigated the effect of ICV administration of IGF-1 on systemic blood pressure and blood flow in selected vascular beds. ICV cannulas were implanted into normal rats and the animals were allowed to recover for 3 to 4 days. The femoral artery and vein were cannulated for blood pressure monitoring and blood sampling and blood flow probes placed around the iliac, the renal and the superior mesenteric artery were used to assess regional blood flow. ICV injection of IGF-1 resulted in a significant decrease in MAP with a nadir at 15 minutes and a gradual return to baseline by 60 minutes; heart rate increased 40 minutes after the injection. IGF-1 significantly enhanced vascular flow and conductance in the iliac, but not in the renal and superior mesenteric arteries. The effects of IGF-1 were much smaller than those observed previously with equimolar amounts of insulin. We conclude that IGF-1 can decrease MAP by selectively increasing blood flow to skeletal muscle through a direct action on the central nervous system.

Animals↗

Insulin-like growth factor-I decreases mean blood pressure and selectively increases regional blood flow in normal rats.

The insulin-like growth factor-I (IGF-I) and its receptors are widely distributed in peripheral vascular tissue, yet their role in the regulation of blood pressure and blood flow remains unknown. This study investigated the effect of IGF-I on blood pressure and selected regional blood flow in normal Wistar rats anesthetized with chloralose/urethane. The femoral artery was cannulated and used to monitor arterial blood pressure. Electromagnetic flow probes were placed around the left common iliac artery, left renal artery, and the superior mesenteric artery, and used to measure blood flow. IGF-I (2.6 micrograms, 5.1 or 10.3 nmol/animal Iv) was injected as a bolus into the femoral vein. Following the injection of IGF-I (10.3 nmol), we observed a significant decrease of plasma glucose (57%) and a significant decrease of mean arterial pressure (MAP) that continued to decline throughout the 60-min experimental period. IGF-I (5.1 nmol) significantly decreased blood glucose by 44% and decreased the MAP by 14% with a nadir at 15 min and recovery after 60 min. A smaller dose of IGF-I (2.6 nmol) did not significantly decrease the blood glucose but resulted in a slight but significant decrease in MAP. The heart rate was increased by 10.3 and 5.1 but not 2.5 nmol of IGF-I. IGF-I (10.3 nmol) was associated with regional vascular responses with a preferential increase in flow of the iliac and superior mesenteric vessels, measured as vascular conductance. IGF-I (5.1 and 2.6 nmol) increased preferentially renal vascular conductance. Preinfusion with L-NAME, a nitric oxide inhibitor, inhibited the effects of IGF-I on flow. We conclude that IGF-I can selectively dilate vascular beds leading to a decrease in blood pressure and that the response to IGF-I is mediated by nitric oxide.

Animals↗

Metoclopramide does not inhibit atrial natriuretic factor-stimulated diuresis in man.

BACKGROUND: An understanding of the reflex hormonal responses that occur with a redistribution of the blood volume upon exposure to microgravity or during water immersion is operationally relevant. Further, dopamine receptor antagonists, which are used in the treatment of the motion sickness induced by microgravity, or at sea, may affect fluid metabolism. Atrial natriuretic factor (ANF) is a potent diuretic and natriuretic hormone that is released following central blood volume expansion in man. ANF is also a potent inhibitor of angiotensin- and potassium-stimulated aldosterone release. HYPOTHESIS: Since ANF-induced diuresis may be mediated by dopamine, we sought to determine whether inhibition of dopamine receptors blocks ANF-induced natriuresis and diuresis. Also, since ANF has been shown to inhibit aldosterone secretion induced by adrenocorticotropic hormone (ACTH) in vitro, we investigated whether ANF decreases aldosterone in man infused with exogenous ACTH. METHODS AND RESULTS: In six healthy, sodium-replete men, infusion of synthetic ANF (0.01 microgram.kg.min, Anaritide, Wyeth Laboratories) significantly increased urine flow from 7.1 +/- 0.7 to 11.7 +/- 1.8 ml.min-1 (p < 0.05) and decreased aldosterone from 74.7 +/- 9.0 to 55.8 +/- 6.5 pg.ml-1 (p = N.S.). Metoclopramide (Met), a dopaminergic antagonist, increased plasma aldosterone from 104.5 +/- 8.9 to 163 +/- 12.5 pg.ml-1 (p < 0.05). ANF-induced diuresis was not inhibited by Met, but ANF significantly inhibited Met-stimulated increases in plasma aldosterone. ANF did not attenuate ACTH-stimulated increases in plasma aldosterone. Also, ANF-induced diuresis and natriuresis were not affected by concomitant infusions of ACTH, but the ANF-induced kaliuresis was significantly attenuated by ACTH. CONCLUSION: These studies suggest: a) Synthetic ANF induces a diuresis, natriuresis and kaliuresis; b) the D2 receptor antagonist Met increases plasma aldosterone; c) ANF-induced diuresis is not subject to dopaminergic blockade with Met, but Met-induced increases in plasma aldosterone are inhibited by ANF; and d) ANF does not attenuate ACTH-stimulated increases in mineralocorticoid production. These studies have operational significance, as they demonstrate that D2 dopaminergic blockade by the antinausea agent metoclopramide does not prevent the effects of increased ANF in response to central volume expansion such as occurs during exposure to microgravity or following water immersion.

Adrenocorticotropic Hormone↗

Nocturnal hypotension in older men with sleep-related breathing disorders.

Sleeping and awake blood pressures were related to sleep oxygenation and awake control of breathing in hypertensive and normotensive older men. During sleep, episodes of both hypertension and hypotension were observed, but hypotension was prominent. Five of 26 subjects exhibited episodes with a minimum mean arterial pressure of 60 mm Hg or less. These hypotensive episodes were associated with hemoglobin desaturation below 80 percent, secondary to sleep-related breathing disorders, and elevated supine nasopharyngeal airway resistance. Hypotensive subjects were habitual snorers. Waking hypertension was not associated with sleep-related breathing disorders in this older sample. In some older persons with sleep-related breathing disorders, sympathetic reflexes may be impaired, permitting hypotension and risk of circulatory failure. Epidemiologic evidence supports the hypothesis that this mechanism can explain the elevated incidence of cerebral infarction during sleep.

Aged↗

Effect of indomethacin in the late phase of coxsackievirus myocarditis in a murine model.

Previous studies have shown that indomethacin administered during the early phase of experimental myocarditis may exacerbate the disease process. It is unknown whether late administration of this agent is safe. Therefore, the effect of indomethacin administration during the late phase of coxsackievirus B3 murine myocarditis was investigated. Forty 3-week-old CD1 mice each received a 3 x 10(4) median tissue culture-infective dose of coxsackievirus intraperitoneally. On day 10 of infection, mice were randomized to receive either indomethacin or normal saline solution for 10 days, and 10 mice from each group were killed on days 20 and 30 of infection. Heart weight and size and serum atrial natriuretic peptide were similar in both groups on days 20 and 30. On day 20, pathologic scores for the degree of inflammation and necrosis were 1.7 and 1.0 for the indomethacin group versus 1.4 and 1.7 for the saline solution group. On day 30, pathologic scores were 0.3 and 0.6 for the indomethacin group versus 0.5 and 0.6 for the saline solution group. In addition, mineralization was absent in indomethacin-treated animals on day 20 after infection, but it was present in half of the control animals at that time. The degree of mineralization did not differ on day 30 between the two groups. These findings suggest that indomethacin given in the late phase of coxsackievirus myocarditis has no deleterious effects at 30 days.

Animals↗

Comparison of hydrochlorothiazide and sustained-release diltiazem for mild-to-moderate systemic hypertension.

The safety and efficacy of sustained-release diltiazem, 120 to 180 mg twice daily, was compared with those of hydrochlorothiazide, 25 to 50 mg twice daily, in 207 patients with mild-to-moderate hypertension (supine diastolic blood pressure [BP] 95 to 114 mm Hg) using a baseline, placebo, parallel-design study protocol. All patients received placebo for 2 to 4 weeks, followed by either study drug during the double-blind phase, titrated over 8 weeks to achieve a goal of supine diastolic BP reduction of at least 10 mm Hg and/or a diastolic BP of less than 90 mm Hg. Patients not achieving the treatment goal with either drug alone received the other drug in combination. Both drugs produced significant decreases in supine and upright BP throughout the 26-week study. The magnitude of decrease in mean supine diastolic BP was similar for both drugs as monotherapy at week 14 (-11.4 and -12.1 mm Hg, respectively). Hydrochlorothiazide produced significantly greater reductions at week 14 in mean supine systolic BP than sustained-release diltiazem (-19.5 and -12.7 mm Hg, respectively). The difference in mean supine diastolic BP reduction with the 2 drugs diminished when hydrochlorothiazide (50 mg/day) was compared with sustained-release diltiazem. The BP effects were sustained for 6 months with both drugs. The 2 drugs appeared to lower BP more in patients older than 60 years and more in black than in white patients. The combination of the 2 drugs decreased supine diastolic BP to goal levels in about 56% of the patients not achieving goal with either drug alone. Adverse effects were minimal with either drug alone and in combination, except for hypokalemia, which increased with thiazide alone and in combination.

Adult↗

Catecholamines in critical care.

Catecholamines (norepinephrine, epinephrine, and dopamine) are released into circulation in response to stress and injury and as part of the body's attempt at vasoregulation in response to circulatory failure. Norepinephrine is released from sympathetic nerve terminal, and epinephrine and dopamine are released from the adrenal medulla. Plasma levels of these catecholamines have been reported to be elevated in various clinical settings: congestive heart failure, myocardial infarction, cardiopulmonary bypass, diabetic ketoacidosis, hypoxia, hemorrhage, and septic shock. These amines have both beneficial and detrimental effects on survival. Both norepinephrine and dopamine are often employed in the critically ill to selectively increase cardiocerebral and renal blood flow, respectively.

Animals↗

Diuretics versus calcium-channel blockers in systemic hypertension: a preliminary multicenter experience with hydrochlorothiazide and sustained-release diltiazem.

The safety and efficacy of sustained-release diltiazem 120 to 180 mg, 2 times a day, were compared with hydrochlorothiazide 25 to 50 mg, 2 times a day, and the combination of diltiazem and hydrochlorothiazide in 56 patients with mild to moderate hypertension (supine diastolic blood pressure between 95 and 114 mm Hg) using a placebo-controlled, parallel-design protocol. Data from an additional 21 patients were evaluated for safety only. The data reported herein represent the preliminary experience from a larger 200-patient multicenter study. All patients received placebo for 4 weeks, followed by either hydrochlorothiazide or diltiazem titrated to achieve a diastolic blood pressure reduction of greater than or equal to 10 mm Hg to reach a goal supine diastolic blood pressure of less than 90 mm Hg. Patients not achieving the treatment goal received hydrochlorothiazide plus diltiazem. At week 14, on maintenance monotherapy, diltiazem and hydrochlorothiazide produced comparable reductions in blood pressure from placebo baseline (160.3 +/- 24.3/101.7 +/- 5.5 to 145.2 +/- 24.1/89.8 +/- 7.4 mm Hg with diltiazem, 156.0 +/- 15.6/103.7 +/- 4.7 to 134.1 +/- 12.5/89.2 +/- 9.5 mm Hg with hydrochlorothiazide, p less than 0.001 for both). Diltiazem and hydrochlorothiazide achieved goal blood pressure in 42% and 45% of patients, respectively. The effects in responders were sustained for 6 months. In patients who did not achieve the treatment goal, 63% responded to diltiazem plus hydrochlorothiazide.No clinically significant postural hypotension was observed on any regimen. Heart rate was slightly lower with diltiazem than with hydrochlorothiazide. Adverse effects were minimal with diltiazem, hydrochlorothiazide and diltiazem plus hydrochlorothiazide but more hypokalemia occurred with hydrochlorothiazide.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗

Teaching job independence and flexibility to mentally retarded students through the use of a self-control package.

We examined mentally retarded individuals' use of picture cues and self-monitoring to initiate a series of tasks of varying type and order. Four severely to moderately retarded high school students participating in a vocational training program were trained to use a picture-cue system. The system consisted of photographs of vocational tasks that were inserted in the assigned order in a photoalbum sheet; self-management was accomplished by marking off each photo after its corresponding task was completed. Students were assigned seven tasks from a pool of 13 each day. Results indicated that the students quickly learned to use the picture-cue system to change tasks throughout their workday without trainer prompts and that performance was maintained as trainer feedback and presence were decreased. At the end of the study, two students who were exposed to novel photographs were able to initiate independently after only minimal training, suggesting that the use of the picture-cue system had become a generalized skill.

Adolescent↗

Awake abnormalities of control of breathing and of the upper airway. Occurrence in healthy older men with nocturnal disordered breathing.

We hypothesized that preexisting diminished chemical control of breathing and narrowing of the upper airway are associated with sleep-related disordered breathing (SRDB) in healthy older men. Twenty-six subjects, aged 55 to 70, were studied. An SRDB episode was a decrease in arterial oxygen saturation (SaO2) of at least 4 percent. Some of these episodes occurred while airflow continued (ie, nonapneic episodes), and the rest occurred with apnea. Sixteen subjects had greater than 12 SRDB episodes per hour of sleep (SRDB subjects) and ten subjects had less than 8 episodes per hour (controls). During waking, the mean hypercapnic ventilatory response was lower, and the mean supine nasal airway resistance (SNAR) was higher in SRDB subjects than in control subjects. During waking, 12 of 16 SRDB subjects had one or more respiratory abnormalities: four had an elevated SNAR; four had a reduced hypercapnic response; three had a reduced hypoxic ventilatory response, and two had an abnormal flow-volume curve. Only one of ten control subjects had a respiratory abnormality (an elevated SNAR). Also, the number of SRDB episodes per hour correlated with the SNAR, and the minimum SaO2 during sleep correlated with the magnitude of the hypercapnic response. We conclude that SRDB occurs commonly in otherwise healthy older men with preexisting abnormalities of control of breathing or of the upper airway.

Age Factors↗