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Biomedical subjects

R G Hoffmann

Publications and source records attributed to R G Hoffmann.

At least 19 recordsLinked to original sources

Effect of omega-3 fatty acids on the vascular response to angiotensin in normotensive men.

There is a widespread interest in fish oil as a dietary supplement and possible nonpharmacologic adjunct in the treatment of hypertension. The effect of dietary fish oil on blood pressure is controversial and the effect on systemic hemodynamics and regional vascular reactivity in humans is unknown. To address these questions, a double-blind, placebo-controlled, crossover study on the effect of dietary fish oil substitution was performed during a carefully controlled diet in 8 normotensive men. Systemic hemodynamics and the forearm vascular response to intrabrachial artery infusions of norepinephrine, phentolamine and angiotensin II were obtained. Compared with a safflower oil placebo, dietary fish oil had no effect on cardiac output (6.42 +/- 0.38 vs 6.87 +/- 0.28 liters/min, p = not significant) or 24-hour blood pressure (122/68 +/- 3/3 vs 122/68 +/- 3/2 mm Hg, p = not significant). The vascular response to norepinephrine and phentolamine was unchanged. Fish oil, however, significantly (p < 0.05) reduced forearm vascular resistance responses to angiotensin II. These changes were associated with a reduction in plasma triglycerides (64 +/- 9 vs 39 +/- 4 mg/dl, p = 0.02) and an increase in plasma eicosapentaenoic acid levels (0.51 +/- 0.25 vs 1.72 +/- 0.35 microM, p < 0.05). Substitution of a moderate dose of fish oil for fat in a "Western diet" selectively attenuates the vascular response to angiotensin independently of changes in alpha-adrenergic vasoconstriction or systemic hemodynamics.

Adult

Cholesterol and coronary artery disease: age as an effect modifier.

An elevation of serum cholesterol has been one of the more frequently cited risk factors for coronary heart disease, found in both case-control and cohort studies. As a result, this country has undertaken massive screening of adults older than 20 years of age in an attempt to identify those persons with cholesterol levels greater than 200 mg/dl, and follow up with an active approach for intervention. The suggested cutpoints for borderline (200-240 mg/dl), and definite (> or = 240 mg/dl) hypercholesterolemia have been applied to all age groups despite suggestions of a diminution of risk conferred by cholesterol in the elderly. This study of 2544 white men undergoing coronary angiography shows that for all men, aged 25-84 years, plasma cholesterol levels were associated with an increase in coronary artery occlusion (rs = 0.15, p < 0.01). However, when stratified by age, this association held only for the younger men, the association diminishing to near zero in the oldest age group. The negative interaction between cholesterol levels and age in predicting coronary artery disease proved highly significant (p < 0.001) in multivariable linear regression analysis, suggesting that cholesterol levels are much less predictive of coronary artery disease in the elderly as compared to the young. These results point to the need for a more finely tuned set of criteria for the evaluation of hypercholesterolemia, one that takes into account the age of the screenee.

Adult

Basal metabolic rate of Colombian children 2-16 y of age: ethnicity and nutritional status.

Measurements of basal metabolic rate (BMR) were made in 528 children 2-16 y of age living in underprivileged areas of the city of Cali, Colombia (153 control and 186 undernourished boys, 93 control and 96 undernourished girls). The data are related to BMR calculated from the equations of Schofield and to estimates of the lean body mass (LBM). The ethnic composition of the subjects was 80% mestizo (mixed European and South Amerindian ancestry), 15% black, and 5% white. The data do not show any variations due to race in these subjects. The Schofield equations overestimate the BMR of boys by approximately 6% whereas the estimation of BMR in girls is not significantly different from measured values. More than 65% of the variation in BMR of both nutritionally normal and undernourished boys and girls is explained by variation in body size as estimated by the LBM.

Adolescent

Environmental risk factors in endemic pemphigus foliaceus (Fogo selvagem). "The Cooperative Group on Fogo Selvagem Research".

Endemic pemphigus foliaceus or Fogo selvagem (FS) is an epidermal organ-specific autoimmune disease mediated by autoantibodies. Individuals at risk are peasants who live and work on farms located in the interior of certain endemic states of Brazil. This case-control study compares a group of 52 FS patients with 52 patients suffering from other dermatoses admitted and followed at the hospital for pemphigus (Hospital do Penfigo) in the city of Goiania, state of Goias. Patients and controls matched 1:1 by age, sex, and occupation were examined by two dermatologists at the time of admission and asked to respond to a prepared questionnaire. This questionnaire concerned current and past (1 and 5 years) exposure to environmental risk factors. The following risk factors were assessed: black fly bites, presence of rodents at home, exposure to cereal dust, exposure to fumes or dust released by tree and shrub removal, and exposure to insecticides. Relative risks were estimated from tabulated data by the odds ratio and tested for significance by the chi-square test. The 95% confidence interval for the odds ratio was also calculated for each of the risk factors. The only risk factor showing an odds ratio significantly different from one was exposure to simuliidae bites (odds ratio 4.7, p less than 0.001). This study reinforces the hypothesis that chronic exposure to black fly antigens may precipitate IgG4 antibody formation in predisposed individuals. These antibodies in turn may cross-react with epidermal antigens and cause acantholysis and the clinical expression of the disease known as FS.

Adolescent

Myogenic mechanism for peristalsis in opossum smooth muscle esophagus.

We studied the propagation of phasic contractions initiated by tetraethylammonium (TEA, 1-10 mM), high K+ concentration (10-30 mM), and bethanechol (10(-6) to 10(-2) M) in a whole organ in vitro preparation of the opossum smooth muscle esophagus. TEA initiated phasic contractions that began at all sites along the smooth muscle esophagus and propagated in both directions with a velocity similar to that of primary peristalsis. Blockade of neural transmission by tetrodotoxin (TTX, 10(-7) M) did not prevent contraction propagation. Although a majority of contractions initiated by TEA did not propagate the full length of the esophageal specimen, with the addition of TTX most contractions initiated by TEA did propagate the full specimen length in either direction. High K+ concentration and bethanechol elicited propagated contractions similar to those initiated by TEA. We conclude that 1) a myogenic mechanism exists for propagation of contractions along the smooth muscle esophagus and 2) intramural inhibitory nerves modulate the extent of myogenic propagation in the ascending as well as descending direction. We suggest that esophageal peristalsis may occur by myogenic propagation of contractions that are normally initiated in the proximal smooth muscle esophagus by excitatory nerves. Intramural inhibitory nerves may inhibit retrograde propagation as well as mediate descending inhibition in advance of the peristaltic wave.

Animals

Low- and high-frequency insulin secretion pulses in normal subjects and pancreas transplant recipients: role of extrinsic innervation.

Low-frequency ultradian and high-frequency insulin secretion pulses were studied in normal subjects and in metabolically stable pancreas transplant recipients. Insulin secretion pulsatility was evaluated after deconvoluting the pulsatile plasma C peptide concentrations with its kinetic coefficients. In normal subjects, ultradian insulin secretion pulses with periodicities of 75-115 min were consistently observed during the 24-h secretory cycle. Pulse period and relative amplitude during the overnight rest (95 +/- 4 min and 27.6 +/- 2.4%) were similar to those during the steady state of continuous enteral feeding (93 +/- 5 min and 32.6 +/- 3.3%). Sampling at 2-min intervals revealed the presence of high-frequency insulin secretion pulses with periodicities of 14-20 min and an average amplitude of 46.6 +/- 5.4%. Pancreas transplant recipients had normal fasting and fed insulin secretion rates. Both low- and high-frequency insulin secretion pulses were present. The high-frequency pulse characteristics were identical to normal. Low-frequency ultradian pulse periodicity was normal but pulse amplitude was increased. Thus, ultradian insulin secretory pulsatility is a consistent feature in normal subjects. The low- and high-frequency secretion pulsatilities are generated independent of extrinsic innervation. Autonomic innervation might modulate low-frequency ultradian pulse amplitude exerting a dampening effect.

Adult

Does aging intensify the insulin resistance of human obesity?

Relative insulin sensitivity in aging and obesity was studied during 6-h euglycemic-hyperinsulinemic clamp procedures in seven nonobese weight-matched premenopausal (Pre-M) and postmenopausal (Post-M) women and in nine weight-matched obese Pre-M and Post-M subjects. Peripheral glucose disappearance rates (Rd) and endogenous glucose production rates (EGPR) were measured during baseline (0-2 h) and at insulin delivery rates of 10 (2-4 h) and 40 mU/m2.min (4-6 h). Baseline Rd and EGPR were comparable in the four groups. In Pre-M nonobese women, Rd rose 1.6- and 4-fold above baseline, respectively, at 2-4 and 4-6 h. In all other groups Rd did not change at the lower insulin delivery rate and rose only 2-fold above baseline at the higher delivery rate. EGPR was suppressed 61% and 100% at the two insulin infusion rates, respectively, in Pre-M nonobese subjects. Similar normal suppression was observed in Post-M nonobese individuals. However, in both obese groups, EGPR suppression was comparable and significantly less than that in nonobese groups. These results confirm the presence of peripheral tissue insulin resistance in both obese and aging women. However, in aging, unlike obesity, EGPR is normally suppressed by insulin. In addition, aging does not appear to intensify the insulin resistance of obese states when both coexist in the same individual.

Adult

Optimal lead positioning for postoperative atrial pacing.

Temporary atrial pacing leads have uncontested utility for diagnosis and treatment of postoperative supraventricular arrhythmias. Sensing and capture thresholds may be inconsistent, however. We evaluated intraoperative atrial sensing amplitude and capture thresholds in 25 patients after coronary bypass using six bipolar and four unipolar lead combinations based on four lead positions: A, atrial appendage; B, 1 cm above the presumed sinoatrial node at the atrial-superior-vena caval junction; C, interatrial groove at the right superior pulmonary vein; and D, caudal inferolateral free wall. Unipolar lead B and bipolar lead B-D had the best voltage pacing threshold and system resistance (p less than 0.05). The lowest current was also observed with unipolar lead B and bipolar lead B-D, but the difference was not significant (p greater than 0.05). P-wave amplitude was not significantly different for any lead combination. Location C, in unipolar or bipolar combinations, frequently paced the phrenic nerve. These data provide new guidelines for establishment of postoperative temporary atrial pacing leads.

Arrhythmias, Cardiac

Potassium administration reduces and potassium deprivation increases urinary calcium excretion in healthy adults [corrected].

This study was undertaken to evaluate the effects of dietary K intake, independent of whether the accompanying anion is Cl- or HCO3-, on urinary Ca excretion in healthy adults. The effects of KCl, KHCO3, NaCl and NaHCO3 supplements, 90 mmol/day for four days, were compared in ten subjects fed normal constant diets. Using synthetic diets, the effects of dietary KCl-deprivation for five days followed by recovery were assessed in four subjects and of KHCO3-deprivation for five days followed by recovery were assessed in four subjects. On the fourth day of salt administration, daily urinary Ca excretion and fasting UCa V/GFR were lower during the administration of KCl than during NaCl supplements (delta = -1.11 +/- 0.28 SEM mmol/day; P less than 0.005 and -0.0077 +/- 0.0022 mmol/liter GFR; P less than 0.01), and lower during KHCO3 than during control (-1.26 +/- 0.29 mmol/day; P less than 0.005 and -0.0069 +/- 0.0019 mmol/liter GFR; P = 0.005). Both dietary KCl and KHCO3 deprivation (mean reduction in dietary K intake -67 +/- 8 mmol/day) were accompanied by an increase in daily urinary Ca excretion and fasting UCaV/GFR that averaged on the fifth day +1.31 +/- 0.25 mmol/day (P less than 0.005) and +0.0069 +/- 0.0012 mmol/liter GFR (P less than 0.005) above control. Both daily urinary Ca excretion and fasting UCaV/GFR returned toward or to control at the end of recovery. These observations indicate that: 1) KHCO3 decreases fasting and 24-hour urinary Ca excretion; 2) KCl nor NaHCO3, unlike NaCl, do not increase fasting or 24-hour Ca excretion and 3) K deprivation increases both fasting and 24-hour urinary Ca excretion whether the accompanying anion is Cl- or HCO3-. The mechanisms for this effect of K may be mediated by: 1) alterations in ECF volume, since transient increases in urinary Na and Cl excretion and weight loss accompanied KCl or KHCO3 administration, while persistent reductions in urinary Na and Cl excretion and a trend for weight gain accompanied K deprivation; 2) K mediated alterations in renal tubular phosphate transport and renal synthesis of 1.25-(OH)2-vitamin D, since KCl or KHCO3 administration tended to be accompanied by a rise in fasting serum PO4 and TmPO4 and a fall in fasting UPO4 V/GFR, a fall in serum 1,25-(OH)2-D and a decrease in fasting UCa V/GFR, while dietary KCl or KHCO3 deprivation were accompanied by a reverse sequence.

Adult

NaCl induces differential changes of regional vascular reactivity in salt-sensitive versus salt-resistant men.

The objective of our study was to determine the structural or functional factors which increase forearm vascular resistance (FAVR) during a high NaCl diet in salt-sensitive (SS) volunteers. We studied the effects of 20 v 200 mEq/day NaCl diets on FAVR responses to norepinephrine (NE), angiotensin II (AII), nitroprusside, verapamil, and ischemia in 27 men. Twelve men had supine mean arterial pressure (MAP) on high NaCl which was greater than or equal to 5% above MAP on low NaCl and were consequently labeled SS. Eleven subjects had lower MAP on the high NaCl diet and were classified salt-resistant (SR). Basal FAVR was greater in SS (P less than .005) and unchanged in SR subjects on high (v low) NaCl. FAVR responses to NE and nitroprusside were not different between the two diets within either the SS or SR subgroups. FAVR responses to AII decreased during high NaCl in the SR (P less than .01), but not in the SS subset. The response to phentolamine and verapamil increased in SS (P less than or equal to .05) and tended to decrease in SR subjects (P less than .15) during high NaCl. In contrast, the vasodilator response to ischemia was impaired in the SS (P = .02) and enhanced in the SR (P = .02) group on high v low NaCl. Enhanced alpha-adrenergic and Ca2+ channel (verapamil)-dependent vascular tone probably contribute to the greater baseline FAVR in SS subjects on high NaCl. Failure to decrease vasoconstrictor responses to AII may indirectly contribute to their maladjustment of FAVR.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult

Depression of baroreflex control of heart rate by halothane in growing piglets.

The purpose this study was to examine the effects of halothane on baroreflex control of heart rate in developing swine. Serial tests of baroreflex function were performed over the first 2 months of life in eight piglets in the conscious state and during anesthesia with 0.45, 0.9, and 1.35% halothane. Systemic blood pressure was increased with phenylephrine (pressor test) and decreased with nitroprusside (depressor test), and stimulus-response curves relating mean blood pressure to heart rate were constructed. Baroreflex sensitivity was determined as the slope of the linear portion of the curve. Halothane markedly depressed baroreflex sensitivity at all ages in a dose-dependent manner (conscious greater than 0.45% greater than 0.9%, 1.35%). Increasing age was accompanied by decreasing baroreflex sensitivity in both the conscious and the anesthetized states. The difference in baroreflex sensitivity between conscious and anesthetized states did not change with age for the depressor test (tachycardia response), but it did change with age for the pressor test (bradycardia response). For this test, conscious values converged toward anesthetized values at higher ages; therefore, there was relatively less depression by halothane at older ages. Halothane also decreased resting heart rate and decreased the limits and narrowed the range of the baroreflex heart rate response. Increasing age was accompanied by a decreasing resting heart rate and by decreasing limits and a narrowing range of the baroreflex response. The effect of halothane on heart rate variables was similar at all ages. Halothane decreased resting blood pressure and decreased the lower limit and widened the span of the baroreflex blood pressure range.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals

Myogenic oscillatory mechanism for opossum esophageal smooth muscle contractions.

We evaluated the control of phasic contractions in opossum esophageal circular smooth muscle by determining the contractile response in vitro to agents that cause membrane depolarization and excitation by different mechanisms. Transverse muscle strips taken from different sites along the length of the smooth muscle esophagus were exposed to progressively increasing concentrations of tetraethylammonium (1-30 mM), K+ (4.6-30 mM), or bethanechol (10(-6) to 10(-2) M). In normally inactive esophageal circular smooth muscle, tetraethylammonium and high K+ concentration elicited phasic contractions that were not blocked by atropine and tetrodotoxin. Bethanechol, an M2 muscarinic receptor agonist that acts selectively on smooth muscle, elicited phasic contractions that were not blocked by tetrodotoxin. We conclude that a latent myogenic oscillatory mechanism for control of phasic contractions exists in esophageal circular smooth muscle and that it may be activated by nonspecific excitation of the smooth muscle membrane. We suggest that this myogenic oscillatory mechanism is likely excited and modulated by nerves.

Animals

Plasma exchange in chronic progressive multiple sclerosis: a long-term study.

Plasma exchange (PE) was shown in a previous double-blind randomized controlled study to confer significant additional benefit at 1 year upon patients with chronic progressive multiple sclerosis (CPMS) treated with immunosuppressive drug therapy (ISDT). Efficacy over an extended term, indications for retreatment, and long-term toxicity are dealt with in this analysis of a larger number of patients. During the past 7 years, 200 patients with CPMS have been treated with PE and low-dose ISDT at this center. Improvement on the Kurtzke Disability Status Scale by one or more steps post-therapy and at 3-year follow-up is significant by comparison with pre-PE disability status. Clinical improvement was maintained in the majority of patients, reaching as far as a 6-year follow-up. Major life-threatening complications attributable to this combined therapy were not observed.

Adult

Actions of halothane, isoflurane, and enflurane on the regional action potential characteristics of canine Purkinje fibers.

The effects of halothane, isoflurane, and enflurane on proximal (false tendon) and distal (apical) canine Purkinje fibers were measured in vitro to assess their comparative effects on fibers exhibiting characteristically long (proximal) and short (distal) action potential duration. High- and low-dose anesthetic effects were evaluated in three groups of six left ventricular preparations and were compared with the changes occurring at identical times in six control preparations using analysis of variance with repeated measures. Under control conditions in all groups, the action potential duration, measured at 90% repolarization (APD90, mean +/- SEM), of proximal fibers was longer than that of distal fibers (320 +/- 16 vs 252 +/- 11 ms, P less than or equal to 0.01). Halothane (0.3 and 0.7 mM), isoflurane (0.4 and 0.8 mM), and enflurane (0.6 and 1.0 mM) produced a dose-dependent decrease (P less than or equal to 0.01) of proximal fiber APD90 with less (P less than or equal to 0.01) change of distal fiber APD90 and reduced (P less than or equal to 0.05) regional differences of APD90 at the higher dose. The decreases of proximal fiber APD90 were greater (P less than or equal to 0.01) for 1.0 mM (1.7 MAC) enflurane (-66 +/- 7 ms) and 0.8 mM (3.0 MAC) isoflurane (-69 +/- 9 ms) than for 0.7 mM (2.9 MAC) halothane (-33 +/- 8 ms). We conclude that the regional actions of anesthetics on Purkinje fiber repolarization may influence conduction during the relative refractory period and the occurrence of arrhythmias associated with disparity of regional refractory characteristics in the ventricular conduction system.

Action Potentials

Comparison of outcome of paramedic-witnessed cardiac arrest in patients younger and older than 70 years.

To obtain further information concerning differences in the mechanism of out-of-hospital cardiac arrest between elderly and younger patients, 381 consecutive patients who experienced out-of-hospital cardiac arrest, and whose arrest was witnessed by paramedics, were studied. In 91% of cases the arrest occurred at the time the patient's cardiac rhythm was monitored. Patients were divided into 2 age groups: elderly patients were greater than 70 years (187) and younger patients were less than 70 years (194). Elderly patients more commonly had a past history of heart failure (25 vs 10%, p less than 0.003) and were more commonly taking digoxin (40 vs 20%, p less than 0.005) and diuretics (35 vs 25%, p less than 0.004). Before the cardiac arrest, elderly patients were more likely to be complaining of dyspnea (53 vs 40%, p less than 0.009), whereas younger patients were more likely to complain of chest pain (27 vs 13%, p less than 0.001). Forty-two percent of younger patients demonstrated ventricular fibrillation as the initial out-of-hospital rhythm associated with the arrest, compared to only 22% of elderly patients (p less than 0.001). Besides patient age, initial cardiac rhythm varied according to the patient's complaint preceding the arrest. Sixty-eight percent of patients with chest pain demonstrated ventricular fibrillation, whereas only 21% of patients with dyspnea demonstrated ventricular fibrillation. Elderly patients could be as successfully resuscitated as younger patients; however, 24% of younger patients survived, compared to only 10% of elderly patients (p less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

Aged

Flow cytometric evaluation of chemosensitive and chemoresistant head and neck tumors.

For patients with head and neck squamous carcinoma, a clinical response to induction chemotherapy has correlated with a survival advantage. Similarly, patients with diploid tumors have displayed a survival advantage when compared with patients with aneuploid tumors. This study examined DNA content in 33 patients who had undergone induction chemotherapy as part of two clinical protocols to determine if there was a correlation between the patients with diploid tumors and the patients with a clinical response to chemotherapy. Although patients with stage III tumors had a longer disease-free survival than stage IV patients (p less than 0.0002), the addition of DNA content information did not improve the ability to predict response. Specifically, there was no correlation between DNA content and the response to chemotherapy. In addition, for this group of patients, a diploid DNA content was not correlated with a survival advantage. We conclude that DNA content information did not add significantly to the prediction of clinical outcome in these patients who received induction chemotherapy.

Carcinoma, Squamous Cell

Development of baroreflex control of heart rate in swine.

The purpose of this study is to describe the developmental course of arterial baroreflex control of heart rate in swine. Tests of baroreflex function were performed with eight conscious piglets serially over their first 2 mo of life. Systemic blood pressure was raised with phenylephrine (pressor test) and lowered with nitroprusside (depressor test), and stimulus-response curves relating heart rate to mean blood pressure were constructed. Baroreflex sensitivity was determined as the slope of the linear portion of the curve. Baroreflex sensitivity decreased with increasing age. Baroreflex sensitivity was not different between pressor and depressor tests except when the piglets were greater than 52 d old and sensitivity was greater with the depressor test. The heart rates at threshold and saturation, and therefore the heart rate response range, shifted to lower heart rates with increasing age. This shift was more than can be accounted for by the simultaneously decreasing resting heart rate.

Age Factors