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Biomedical subjects

B Grubb

Publications and source records attributed to B Grubb.

At least 19 recordsLinked to original sources
PubMed2000

Vasodepressor Syncope.

Neurocardiogenic syncope is a common disorder affecting various individuals of different ages with a wide variety of circumstances and comorbid conditions. Although a large amount of data is available regarding evaluation and treatment options, there is still sufficient latitude for the physician to exercise clinical judgment. We summarize current opinions on treatment here and also add some of our own bias regarding how to manage such patients. The vast majority of patients can be assessed by a reduction of symptomatic episodes with therapy. In all patients, careful follow-up should be made after initiating therapy. Not all patients will obtain complete resolution of symptoms. If episodes of complete syncope are reduced to infrequent dizzy spells, however, this may be satisfactory. In other patients, abrupt syncope may be converted to spells with a sufficient prodromal warning for the patient to take evasive action.

Journal Article↗
PubMed1998

Role of gammaENaC subunit in lung liquid clearance and electrolyte balance in newborn mice. Insights into perinatal adaptation and pseudohypoaldosteronism.

Genetic evidence supports a critical role for the epithelial sodium channel (ENaC) in both clearance of fetal lung liquid at birth and total body electrolyte homeostasis. Evidence from heterologous expression systems suggests that expression of the alphaENaC subunit is essential for channel function, whereas residual channel function can be measured in the absence of beta or gamma subunits. We generated mice without gammaENaC (gammaENaC -/-) to test the role of this subunit in neonatal lung liquid clearance and total body electrolyte balance. Relative to controls, gammaENaC (-/-) pups showed low urinary [K+] and high urinary [Na+] and died between 24 and 36 h, probably from hyperkalemia (gammaENaC -/- 18.3 mEq/l, control littermates 9.7 mEq/l). Newborn gammaENaC (-/-) mice cleared lung liquid more slowly than control littermates, but lung water at 12 h (wet/dry = 5.5) was nearly normal (wet/dry = 5.3). This study suggests that gammaENaC facilitates neonatal lung liquid clearance and is critical for renal Na+ and K+ transport, and that low level Na+ transport may be sufficient for perinatal lung liquid absorption but insufficient to maintain electrolyte balance by the distal nephron. The gammaENaC (-/-) newborn exhibits a phenotype that resembles the clinical manifestations of human neonatal PHA1.

Adaptation, Physiological↗
PubMed1997

A mouse model for the renal salt-wasting syndrome pseudohypoaldosteronism.

Aldosterone-dependent epithelial sodium transport in the distal nephron is mediated by the absorption of sodium through the highly selective, amiloride-sensitive epithelial sodium channel (ENaC) made of three homologous subunits (alpha, beta, and gamma). In human, autosomal recessive mutations of alpha, beta, or gammaENaC subunits cause pseudohypoaldosteronism type 1 (PHA-1), a renal salt-wasting syndrome characterized by severe hypovolemia, high plasma aldosterone, hyponatremia, life-threatening hyperkaliemia, and metabolic acidosis. In the mouse, inactivation of alphaENaC results in failure to clear fetal lung liquid at birth and in early neonatal death, preventing the observation of a PHA-1 renal phenotype. Transgenic expression of alphaENaC driven by a cytomegalovirus promoter in alphaENaC(-/-) knockout mice [alphaENaC(-/-)Tg] rescued the perinatal lethal pulmonary phenotype and partially restored Na+ transport in renal, colonic, and pulmonary epithelia. At days 5-9, however, alphaENaC(-/-)Tg mice showed clinical features of severe PHA-1 with metabolic acidosis, urinary salt-wasting, growth retardation, and 50% mortality. Adult alphaENaC(-/-)Tg survivors exhibited a compensated PHA-1 with normal acid/base and electrolyte values but 6-fold elevation of plasma aldosterone compared with wild-type littermate controls. We conclude that partial restoration of ENaC-mediated Na+ absorption in this transgenic mouse results in a mouse model for PHA-1.

Amiloride↗
PubMed1994

The involvement of N-methyl-D-aspartate (NMDA) and non-NMDA receptors in the responsiveness of rat spinal neurons with input from the chronically inflamed ankle.

Unilateral adjuvant inflammation was induced at the rat ankle 2 or 20 days before an evaluation of the contribution of N-methyl-D-aspartate (NMDA) and non-NMDA receptors to the processing of nociceptive information by wide dynamic range neurons in the spinal cord. Microionophoretic application of either the NMDA receptor antagonists ketamine and DL-2-amino-5-phosphonovalerate (AP5) or the non-NMDA receptor antagonist 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) reduced the responses to innocuous and noxious mechanical stimulation of the inflamed ankle. The pattern of these effects was comparable to that in rats with acute inflammation suggesting that non-NMDA and NMDA receptors are similarly involved in acute, prolonged acute and chronic inflammation-evoked activity.

2-Amino-5-phosphonovalerate↗
PubMed1994

Central dizziness associated with cerebral blood flow disorders.

This retrospective study describes the use of transcranial Doppler (TCD) and history for further defining and diagnosing cerebral blood flow (CBF) disorders in patients with central dizziness. Central dizziness was defined as dizziness of nonlabyrinthine, non-peripheral causes. It was believed that at least some of the causes for central dizziness are not unknown but are associated with CBF disorders. Fifty patients who presented with central dizziness were examined and subsequently tested with TCD. In 33 of 50 cases (66%) a diagnosis could be assigned after TCD; whereas, on the basis of both history and TCD a diagnosis was assigned to 38 patients (76%).

Adolescent↗
PubMed1993

Isobutylmethylxanthine fails to stimulate chloride secretion in cystic fibrosis airway epithelia.

It has been proposed that a combination of an activated adenylyl cyclase and a high concentration of a phosphodiesterase inhibitor (isobutylmethylxanthine [IBMX], 5 mM) stimulates Cl- secretion mediated by the heterologously expressed cystic fibrosis transmembrane regulator protein carrying the most common cystic fibrosis (CF) mutation (delta F508). We tested whether Cl- secretion could be stimulated by this protocol in vitro and in vivo in CF airway epithelia expressing endogenous delta F508 CFTR protein. In cultured airway preparations, forskolin (a direct adenylyl cyclase activator) stimulated Cl- secretion in amiloride-pretreated normal (delta Isc = 7.1 +/- 1.7 microA.cm-2) but not CF tissues (delta Isc = -02 +/- 0.1 microA.cm-2). Unexpectedly, IBMX partially inhibited the forskolin-induced Cl- secretion in normal tissues; IBMX addition had no effect on CF tissues. Direct measurements of cell cAMP concentrations revealed that 0.1 mM IBMX and forskolin produced the maximum levels of cell cAMP levels attainable with this drug combination, and 5 mM IBMX was without further effect. The combination of forskolin (10(-5) M) and isoproterenol, an adenylyl cyclase activator (10(-5) M), produced approximately 3 times higher levels of cAMP than forskolin/IBMX but also did not induce Cl- secretion in CF tissues. Studies of Cl- secretion in vivo, assessed by the transepithelial electric potential difference (PD), showed that isoproterenol (10(-5) M) stimulated Cl- secretion (delta PD = -16.3 +/- 4.3 mV; n = 4) in nasal epithelia of normal subjects but not in CF patients homozygous for the delta F508 mutation (delta PD = -2.6 +/- 1.9 mV; n = 5).(ABSTRACT TRUNCATED AT 250 WORDS)

1-Methyl-3-isobutylxanthine↗
PubMed1990

Clinical signs of androgen excess as risk factors for coronary artery disease.

Women with androgen excess have been found to have higher triglycerides and lower high-density lipoprotein cholesterol concentrations than nonhirsute women and are presumed to be at increased risk of coronary artery disease. However, definitive data linking androgen excess with coronary artery disease is lacking. We evaluated 102 women coming to coronary artery catheterization for signs and symptoms of androgen excess. Hirsutism was found more commonly in those women with confirmed coronary artery disease (chi 2 = 10.11). Waist:hip ratio (an index of android fat distribution) was associated with hirsutism (by ANOVA, F-test) and with coronary artery disease (t-test). The strongest associations were found in older women (aged greater than or equal to 60). Androgen excess in women may signal risk for coronary artery disease.

Acne Vulgaris↗
PubMed1990

Labetalol and MRI as initial medical and diagnostic modalities in a marfanoid patient with expanding ascending aortic aneurysm.

Marfan syndrome is a hereditable disorder of connective tissue that causes several distinct cardiovascular abnormalities, including aortic regurgitation, dissection, and aneurysm. These cardiac manifestations can be identified with echocardiography, computer tomography, and angiography. Standard treatment of an acute hypertensive crisis in Marfan syndrome uses propranolol and sodium nitroprusside. This patient with Marfan syndrome whose case is reported herein presented with chest pain, hypertensive crisis, and aortic insufficiency; labetalol was used successfully to treat the acute hypertensive crisis and magnetic resonance imaging (MRI) was used to differentiate between aortic dissection and an expanding aortic aneurysm. This report is unique in that labetalol was used to control the hypertensive crisis in Marfan syndrome and MRI was used as the initial diagnostic modality in an emergency setting.

Acute Disease↗
PubMed1990

The association of waist hip ratio and angiographically determined coronary artery disease.

Body fat distribution as measured by the ratio of waist circumference to hip circumference (WHR) is now accepted as an important risk factor for a number of diseases. This study evaluated the association of WHR and coronary artery disease (CAD). Measurements included the subjects' height, weight, waist girth, hip girth, significant CAD on coronary angiography, and cholesterol levels. A history of myocardial infarction, angina, diabetes or hypertension was obtained from subject interviews. The subjects were analyzed in two age groups: younger than age 60 (88 men and 39 women) and age 60 or older (85 men and 63 women). For older women the relative odds of CAD comparing women at the 75th percentile of WHR to women at the 25th percentile was 3.67 (P = 0.003), with a 95 percent confidence interval of 1.57-8.57. The relative odds was reduced to 2.80 after adjusting for all other risk factors. WHR was significantly associated with angiographic evidence of CAD in all women combined after adjusting for age (P = 0.0004), but it was not significantly associated with CAD in younger women or in men. The results suggest that in older women the risk of CAD increases with a greater percentage of body fat in the abdomen.

Adipose Tissue↗
PubMed1986

Experimental hypercupremia does not result in increases in copper in lens, iris, or ocular fluids.

Rabbits were continuously administered copper sulfate via subcutaneously implanted osmotic pumps. After one month, plasma, liver, ocular tissues and fluids were analyzed for copper by atomic absorption spectrophotometry. No elevation in copper content of the ocular fluids, lens or iris was noted although, dose-related increases were seen in the plasma and liver indicating that the copper was absorbed and disseminated systemically. It is likely that excess copper, like that which is normally ingested and absorbed, is largely protein-bound in the circulation, preventing crossing of the blood-ocular barrier.

Animals↗
PubMed1984

Some observations on the zinc metabolism of the rabbit lens.

Rabbits' lenses contain about 100 mumol kg-1 wet wt (145 mumol kg-1 water) of zinc. This metal appears to be quite uniformly distributed throughout the organ and more than 90% is firmly incorporated into the tissue so as not to be readily exchangeable. The concentration of Zn in the aqueous and vitreous humors is about 10(-5) M (one-fourth the concentration in the blood serum). Lenses incubated in vitro can accumulate Zn from solutions containing this concentration of the metal. This process is concentration-dependent and is increased following damage produced by metabolic inhibitors. The process probably involves diffusion and is increased in the presence of a low external calcium concentration and the Ca ionophore A 23187. Amino acids which are known to bind zinc did not influence its accumulation by the lens, with the exception of cystine which increased it. Accumulated Zn (using 65Zn as a tracer) was able to leave the lens, but this process was quite slow and was reduced by the presence of lanthanum and low Ca concentrations. It is suggested that Ca and Zn may share common binding sites in the tissue, and they could be utilizing the same channels to cross the cell membrane.

Age Factors↗
PubMed1983

Panting in the emu causes arterial hypoxemia.

The purpose of this study was to determine the effect of heavy thermal panting on arterial oxygen (PaO2) and carbon dioxide (PaCO2) tension in emus. The birds showed no significant change in body temperature during a 3-4 h heat stress caused by increasing ambient air temperature from 21 to 46 degrees C. However, the emus increased their respiratory frequency 10-fold (from 5.3 to 52.9 breaths X min-1). The high respiratory frequency resulted in a slight but significant decrease in PaCO2 (from 33.5 to 29.8 mm Hg), coupled with a slight increase in pH (from 7.449 to 7.469). Paradoxically, these changes were accompanied by a significant decrease in the arterial oxygen tension (from 99.7 to 84.6 mm Hg). The arterial hypoxia suggests hypoventilation while the hypocapnia suggests hyperventilation of the lungs. This could result from various spatial and/or temporal changes in ventilation/perfusion ratios.

Acid-Base Equilibrium↗
PubMed1983

Cardiovascular changes in the exercising emu.

Cardiovascular variables were studied as a function of oxygen consumption in the emu, a large, flightless ratite bird well suited to treadmill exercise. At the highest level of exercise, the birds' rate of oxygen consumption (VO2) was approximately 11.4 times the resting level (4.2 ml kg-1 min-1). Cardiac output was linearly related to VO2, increasing 9.5 ml for each 1 ml increase in oxygen consumption. The increase in cardiac output is similar to that in other birds, but appears to be larger than in mammals. The venous oxygen content dropped during exercise, thus increasing the arteriovenous oxygen content difference. At the highest levels of exercise, heart rate showed a 3.9-fold increase over the resting rate (45.8 beats min-1). The mean resting specific stroke volume was 1.5 ml per kg body mass, which is larger than shown by most mammals. However, birds have larger hearts relative to body mass than do mammals, and stroke volume expressed per gram of heart (0.18 ml g-1) is similar to that for mammals. Stroke volume showed a 1.8-fold increase as a result of exercise in the emus, but a change in heart rate plays a greater role in increasing cardiac output during exercise.

Animals↗
PubMed1981

Infra-red technique for cerebral blood flow: comparison with 133Xenon clearance.

A rapid infra-red optical technique has been developed for the measurement of cerebral blood flow. The method measures optical density changes across the intact skull during the passage of a bolus of the dye. Cardio-Green (CG). The clearance curves obtained for CG boluses are very short (less than 30 sec) in comparison with those obtained with tracers such as 133Xenon (10-30 min) that distribute into cerebral tissue. The volume of distribution of CG is totally intravascular, and the dye is relatively slowly cleared from the body. The important advantages of this spectrophotometric technique are its speed, versatility, and the avoidance of radioactive materials. The differential spectrophotometer used in this study, with trivial modifications, has been used to monitor changes in brain blood volume, oxygen saturation of hemoglobin, and cortical mitochondrial respiratory function, which illustrate the versatility of the technique for neurological assessments.

Animals↗
PubMed1979

Avian cerebral blood flow: influence of the Bohr effect on oxygen supply.

To clarify the problems of altitude tolerance in birds, we studied the combined effect of hypocapnia and hypoxia on cerebral blood flow (CBF) in ducks. CBF was measured by the xenon clearance method. Normocapnic hypoxia causes CBF to increase when the arterial O2 tension (PaO2) falls below 60--70 mmHg. Hypocapnic hypoxia significantly shifts the blood flow curve so that blood flow does not increase until a lower PaO2 (50--60 mmHg) is reached. This gives the appearance that hypocapnia suppresses the hypoxia-induced increase in CBF. However, due to the Bohr effect, the hypocapnic blood contains significantly more O2 than does the normocapnic blood at the same PaO2. Therefore, when CBF is expressed as a function of O2 content, rather than PO2, CBF in the hypocapnic group does not differ significantly from the CBF in the normocapnic group. We interpret this to mean that because of the significantly greater oxygen content of the hypocapnic blood at a given PaO2, the degree of hypoxia experienced by these brains is not as severe as that experienced by the normocapnic brains.

Adaptation, Physiological↗
PubMed1978

Cerebral blood flow in birds: effect of hypoxia.

The effect of hypoxia on cerebral blood flow in ducks was investigated by the rate at which arterially injected xenon-133 was cleared from the duck's brain. A two-component clearance curve resulted, which we have attributed to flow through the grey and white matter. Decreasing the arterial oxygen tension (PaO2) to 75 mmHg had no effect on cerebral blood flow. However, decreasing the PaO2 below 75 mmHg significantly increased blood flow to the fast-clearing compartment. The greatest increase in blood flow was seen when the arterial PO2 was below 50 mmHg. At an arterial PO2 of 30 mmHg, the cerebral blood flow to the fast-clearing compartment was increased more than 600% above the normoxic level. The magnitude of this increase is much greater in the duck than has been reported for mammals at roughly equivalent arterial oxygen tensions. The ability of avian cerebral blood flow to increase at moderate levels of hypoxia, plus the magnitude of the increase, may play a role in the exceptional tolerance of birds to hypoxia.

Animals↗
PubMed1977

The role of adrenoceptors in norepinephrine-stimulated VO2 in muscle.

The purpose of this study was to characterize the norepinephrine (NE)-evoked calorigenic response of an isolated perfused rat muscle preparation into alpha-and/or beta-adrenergic components. Epinephrine was as effective as NE in evoking the increase in oxygen consumption. The alpha-agonist, phenylephrine, was also as effective as NE in eliciting an increase in oxygen consumption by the muscle. Isoproterenol (beta-agonist) had no effect on the VO2 of the preparation. Phentolamine, an alpha-blocker, completely blocked the NE-stimulated VO2. Propranolol (beta-antagonist) could also completely block the NE induced VO2 but this drug was found to be less potent. It was concluded that the NE-induced calorigenic response of muscle cannot be classified either strictly as an alpha-or beta-response, but unlike brown adipose tissue, the alpha-response seems to predominate in skeletal muscle. Also, it appears as though different mechanisms of action may be involved in the NE-stimulated VO2 in skeletal muscle and brown fat.

Adrenergic alpha-Agonists↗