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Biomedical subjects

B Falkner

Publications and source records attributed to B Falkner.

At least 73 records · Page 4Linked to original sources
PubMed1988

Microscopic nephrocalcinosis in cystic fibrosis.

Airway, sweat-duct, and other epithelial cells in patients with cystic fibrosis display abnormal ion transport. To test whether the kidney, the organ most exquisitely adapted for ion transport, has a similar defect, we measured the levels of calcium excretion and searched for microscopic nephrocalcinosis in patients with cystic fibrosis. Thirty-eight specimens of kidney tissue were stained for calcium deposits, and 24-hour levels of urinary calcium excretion were measured in 14 patients and 15 control subjects. Microscopic nephrocalcinosis was observed in 35 of the 38 specimens (92 percent), and hypercalciuria (greater than 182 mg per gram of creatinine) in 5 of the 14 patients (36 percent). Notably, nephrocalcinosis was detected near the time of birth (in six patients under one year old, including two neonates and one stillborn infant), which supports the hypothesis that such renal calcium deposits reflect the genomic defect and are not due to longstanding pulmonary dysfunction, chronic infection, therapeutic agents, or disease progression. None of the patients with hypercalciuria or nephrocalcinosis had clinical evidence of renal dysfunction. The finding of microscopic nephrocalcinosis near the time of birth in patients with cystic fibrosis suggests a primary abnormality of calcium metabolism in the kidney. Studies of the pathophysiologic features of the kidney in cystic fibrosis may elucidate the molecular alterations observed in this disorder.

Adolescent↗
PubMed1988

Sodium sensitivity: a determinant of essential hypertension.

The epidemiologic correlation of chronic dietary salt intake among populations with the prevalence of hypertension has resulted in the concept that sodium plays an etiologic role in the development of essential hypertension (EH). However, the association of sodium intake with blood pressure in individuals within populations has been difficult to demonstrate. The differing human responses to sodium intake are dependent upon the individual level of sodium sensitivity or sodium resistance. Factors associated with sodium sensitivity are race, age, and other dietary factors. More recent investigations have pursued the interaction of sodium intake with other physiologic parameters including neurogenic activity, vascular structure, renal function, and other cations such as potassium and calcium. The observations that some humans demonstrate very little increase in blood pressure despite high levels of sodium intake supports the concept that a high sodium intake alone is not a single causal factor in hypertension. Sodium intake appears to interact with renal excretory capacity and vascular compliance. These varying physiologic functions must be delineated to characterize sodium sensitivity.

Blood Pressure↗
PubMed1986

Cardiovascular characteristics of the young with borderline hypertension.

Borderline hypertension generally describes blood pressure levels at the margins of an established disease state. Prior to adulthood, this definition becomes less clear. Juveniles with blood pressure levels at the extremes of the normal distribution may be borderline hypertensive, hypertensive, or normal. Aberrant mechanisms that progress to essential hypertension have their onset in the young. Evidence is emerging that demonstrates variation in neurogenic function in young people. Other functional and structural variations have also been described prior to adulthood. These observations are beginning to characterize young people having borderline hypertension and also those with a greater risk for progressing to essential hypertension.

Adolescent↗
PubMed1986

Na-K-C1 cotransport and Na pump in red cells of young blacks and blood pressure response to salt loading.

The functional operation of Na and K fluxes, mediated by the furosemide-sensitive (FS) Na-K-C1 cotransport and the ouabain-sensitive Na pump, was studied in a representative young (18-22 years) black population. Cation fluxes (mumol/L cell X hour = FU) were studied prior to salt loading; results were compared with the blood pressure response to chronic oral salt loading. All subjects (n = 26) took 10 g/day NaC1 plus their usual diets for 14 days. A mean arterial blood pressure increase higher than 5 mmHg was considered a sodium-sensitive (SS) response; a response lower than 5 mmHg was considered sodium-insensitive (SI). The Km for Nac to stimulate FS Na efflux was significantly greater in SS (SS = 13.8 +/- 1.39 mmol/L cells, n = 15; SI = 8.5 +/- 0.8 mmol/L cells, n = 11; p less than 0.001). Inward cotransport of Na and K was also studied at constant Nac (13 mmol/L cells) and incubation of 140 mM Na and 4 mM K. No significant differences were found in the Vmax of outward FS Na and K efflux, FS86 Rb, Na influx, net Na movement (efflux minus influx), and the Na/K ratio of inward cotransport. Several parameters of the ouabain-sensitive Na pump (Vmax of the Na efflux, Rb influx, Na/K coupling ratio (2.2), and fresh Nac) were found to be similar in both groups. The results indicate that in young blacks, the Na sensitivity of the blood pressure may be associated with lower affinity for internal Na of the outward Na-K-C1 cotransport system.

Adolescent↗
PubMed1986

Sodium sensitivity, growth and family history of hypertension in young blacks.

The response to chronic oral sodium loading was studied in young adult (18-23 years) blacks. A representative sample of participants (n=40) from previous longitudinal studies had growth measures at age 6-7 years and 11-16 years. Blood pressure, weight and stress-induced reactivity were measured before and after 14 days of 10 g NaCl daily added to the usual diet. A sodium-sensitive response (SS) was an increase in mean arterial pressure (MAP) greater than or equal to 5 mmHg. A sodium-insensitive response (S) was an increase in MAP less than or equal to 5 mmHg. Family history of hypertension (FH+) was determined by self-report. Fifty-three per cent were SS. There were no difference in age-related BP, weight or height between SS and SI in childhood or adolescence. Those with a family history of hypertension had a greater BP response to stress and greater weight change with sodium load. The group which was both SS and FH+ had the highest weight and MAP stress response after sodium load. These results indicate that sodium sensitivity is high among blacks, but does not correlate with childhood growth variables. Sodium sensitivity and FH+ combined produce the greatest stress-induced BP response.

Adolescent↗
PubMed1986

Management of hypertension in children and adolescents.

Secondary causes of hypertension are more frequent in children than in adults; however, essential hypertension does occur in the young. The decision to search for secondary causes rests on the age of the child, the severity of hypertension, the presence of clues in the history or physical examination, and the family history. If nonpharmacologic measures fail to control hypertension and if acute hypertension is not present, a stepped-care approach is suggested.

Adolescent↗
PubMed1986

[Cardiovascular reactivity in young people].

Experimental and clinical evidence has emerged which supports the presence of a stress mediated neurogenic component in the development of essential hypertension (EH). To investigate the relationship of genetic risk for EH and the cardiovascular response to centrally mediated stress in the young, we have studied adolescent offspring of hypertensive and normotensive parents. Compared to the normotensive family history negative controls, those adolescents with mildly elevated blood pressure and at least one parent with RH respond to the central stressor of forced mental arithmetic with a greater and more prolonged elevation in blood pressure (p less than 0.01) and heart rate (p less than 0.1). Those adolescents who were normotensive but also had a parent with EH also had a greater response in the cardiovascular parameters (p less than 0.1) than the family history negative controls. However, this group was mixed with high responders and low responders. Preliminary studies on the effect of sodium on the stress response indicated that salt loading augmented the stress response in family history positive subjects, while no effect was observed in the history negative adolescents. Our studies indicate the presence of an identifiable neurogenic component in early EH. Furthermore, a high sodium intake appears to alter the vascular sensitivity to neurogenic stimuli.

Adolescent↗
PubMed1985

Transdermal clonidine in the treatment of adolescent hypertension.

The effectiveness of transdermally administered clonidine in normalizing blood pressure in 22 adolescents with sustained diastolic hypertension was studied. The clonidine transdermal device consisted of an adhesive disc which delivered a low, but continuous, dose of drug through the skin for at least 1 week. Following a placebo disc, subjects received clonidine with increasing titration every 2 weeks until blood pressure reduction goals (90th percentile) were achieved. In 21 of 22 subjects blood pressure goals were achieved and maintained for 8 weeks of stable dose. Side effects were minimal.

Administration, Topical↗
PubMed1984

Effects of nifedipine and verapamil on isometric and dynamic exercise in normal subjects.

Effects of single- and multiple-dose nifedipine and verapamil in 10 healthy men were compared with the effect of placebo during static and dynamic physical activity. Blood pressure (BP), heart rate (HR), and plasma catecholamine and plasma potassium levels were assessed and quantified at rest and at peak levels of 50% handgrip and at rest and peak treadmill activity during placebo, single- and at 2 multiple-dose levels of each of the drugs. Peak BP responses were blunted by a maximal dosage of 120 mg of verapamil administered twice daily during static activity. No blunting of HR response was observed. BP and HR did not change significantly at any dosage level of nifedipine during static exercise. During isotonic exercise the only significant alteration was a progressive decrease in the peak exercise HR with both verapamil and nifedipine. The plasma potassium level increased with both static and dynamic activity but to no greater level than that seen with placebo. Plasma norepinephrine concentration increased at rest after administration of maximal dosage of nifedipine during both isometric and isotonic phases of the study. This is probably related to the underlying mild to moderate increase in sympathetic tone induced by nifedipine. Overall, the hemodynamic responses to exercise are not blunted with calcium-channel antagonists at the dosages studied.

Blood Pressure↗
PubMed1984

Effects of antihypertensive drugs on cognitive function in adolescents.

The effects of clonidine and hydrochlorothiazide on cognitive function were studied in hypertensive adolescents requiring pharmacologic therapy for blood pressure control. Twenty-four adolescents with persistent blood pressure elevation (greater than 95th%) on placebo were randomized double blind to clonidine or hydrochlorothiazide treatment. A battery of cognitive tests were performed during the placebo phase and after 16 weeks of active therapy. Antihypertensive therapy resulted in significant blood pressure reduction (p less than .01). A slight interactive effect was observed in arithmetic performance (p less than .05). All other parameters of cognitive function were not affected by either treatment.

Adolescent↗
PubMed1983

R-wave amplitude change during aerobic exercise in hypertensive adolescents after treatment.

This study attempts to determine whether the blunted reduction in R-wave amplitude during progressive aerobic exercise observed in adolescents with systemic hypertension could be altered by pharmacologic therapy to reduce blood pressure. Twenty-nine hypertensive adolescents were randomly assigned to treatment with either a diuretic, hydrochlorothiazide, or a centrally acting agent, clonidine. After 16 weeks of therapy, casual blood pressure was significantly reduced in both groups. Repeat exercise stress testing on therapy demonstrated a significant change in R-wave response. In both treatment groups the change in R-wave amplitude during exercise corresponded with the R-wave response pattern observed in normotensive control subjects. These observations indicate that the altered R-wave amplitude response to exercise observed in young hypertensive subjects is reversible and suggest that the altered R-wave response before treatment is related to a higher vascular resistance.

Adolescent↗
PubMed1983

Pharmacokinetics and pharmacodynamics of clonidine in varying states of renal function.

Previous studies have reported a therapeutic window of 0.8 to 2.0 ng/ml within which clonidine exerts its antihypertensive effect. This study was designed to investigate whether there was any loss of blood pressure control when plasma clonidine concentrations exceeded this window owing to its accumulation in renal insufficiency. The results indicate that clonidine concentrations of up to 30 ng/ml in patients with end-stage renal disease (ESRD) can be associated with a maintenance of blood pressure control. It remains to be learned whether this phenomenon of high concentrations and control of blood pressure in our ESRD patient population may be related to altered (decreased) peripheral alpha-receptor sensitivity and inability to develop vasoconstriction. There is precedence for autonomic imbalance and altered tissue sensitivity in ESRD.

Adult↗
PubMed1983

Overview of physiology in senescence.

As one ages, blood pressure and hemodynamic changes become apparent. This is reflected in a fall in cardiac output and a gradual increase in total peripheral-vascular resistance. Systolic hypertension is one of the fundamental abnormalities of the cardiovascular system in the elderly. Baroreceptor function and cerebral blood flow likewise may be compromised and result in altered drug sensitivity. Renal function decreases with age and is manifested by a decrease in renal blood plasma flow and in glomerular filtration rate. There is a gradual blunting of sympathetic nervous system responsiveness demonstrated by a decrease in the activity of the renin-angiotensin-aldosterone system. Finally, pathways of drug biotransformation may be altered, resulting in adverse drug reactions.

Aged↗
PubMed1983

The use of clonidine monotherapy in adolescent hypertension.

The effect of a centrally acting agent (clonidine) vs a diuretic as a single agent was studied in a group of hypertensive adolescents. Following placebo therapy, adolescents with blood pressure greater than 95th percentile were randomized to clonidine 0.1 mg or hydrochlorothiazide 25 mg, each given twice daily. Following 12 weeks' active treatment, those who had not achieved blood pressure goals proceeded to clonidine 0.2 mg or hydrochlorothiazide 50 mg twice daily. Blood pressure and clinical assessment was performed at two-week intervals. Cardiovascular response to mental stress and pre-post stress catecholamines were obtained prior to active therapy and during therapy. Clonidine therapy significantly lowered systolic and diastolic pressure and heart rate (p less than .01). Hydrochlorothiazide significantly lowered systolic pressure only. Mental stress testing resulted in a lower diastolic pressure and heart rate response (p less than .01), with lower norepinephrine in the clonidine-treated group. The diuretic group had higher plasma norepinephrine and no significant reduction in stress response. Hypertensive juveniles may be more sensitive to central control of blood pressure and more resistant to diuretics.

Adolescent↗