Problems and pitfalls in the assay of pentamidine. Implications for clinical use.
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Chromatography, High Pressure Liquid↗
Biomedical subjects
J E Hall
Publications and source records attributed to J E Hall.
The detection and documentation of trace wound patterns by use of an alternative light source.
This article is a discussion of the use of narrow-band light sources coupled with cameras equipped with band-pass filters to document patterned injuries on human skin. Several case reports are included.
Adult↗
Control of blood pressure by the renin-angiotensin-aldosterone system.
Modification of the renin-angiotensin system, part of a powerful feedback system for long-term control of arterial pressure and volume homeostasis, through use of angiotensin-converting enzyme (ACE) inhibitors, offers a powerful means of reducing blood pressure in many hypertensive patients. There is considerable evidence to suggest that the chronic renal and blood pressure actions of ACE inhibitors are mediated mainly by blockade of angiotensin II formation, rather than by other effects such as increased levels of kinins or prostaglandins. The long-term actions of angiotensin II and aldosterone on blood pressure are closely intertwined with their effects on volume homeostasis and the renal pressure natriuresis mechanism. In most instances, changes in angiotensin II and aldosterone act to amplify the effectiveness of pressure natriuresis and minimize changes in blood pressure needed to maintain sodium balance. When angiotensin II or aldosterone levels are inappropriately elevated, the antinatriuretic effects of these hormones shift pressure natriuresis to higher levels, thereby necessitating increased blood pressure to maintain sodium balance. Control of renal excretory function and modulation of pressure natriuresis by angiotensin II is mediated by intrarenal and extrarenal effects, including stimulation of aldosterone secretion. Current evidence indicates that the intrarenal effects of angiotensin II are quantitatively more important than changes in aldosterone in regulating renal excretion and arterial pressure. The intrarenal actions of angiotensin II include a direct effect on tubular sodium transport as well as a potent constrictor action on efferent arterioles, which increases reabsorption by altering peritubular capillary forces. The constrictor effect of angiotensin II on efferent arterioles also helps to stabilize glomerular filtration rate and therefore excretion of metabolic waste products, an action that may be particularly important when renal perfusion is impaired (e.g., in renal artery stenosis or heart failure).
Angiotensin II↗
Sequence variation in hepatitis C viral isolates.
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Amino Acid Sequence↗
Renal function in one-kidney, one-clip hypertension and low renin essential hypertension.
One-kidney, one-clip hypertension (1-K, 1-C HT) is initiated by increased preglomerular resistance which decreases nephron perfusion and causes several intrarenal changes that lead to increased mean arterial pressure (MAP). Elevated MAP serves to return nephron perfusion and sodium excretion to normal, so that fluid intake and output are balanced. Increased MAP usually occurs through volume homeostasis mechanisms that initially raise cardiac output and later elevate total peripheral vascular resistance via autoregulatory adjustments. However, if adequate volume is unavailable because of sodium restriction, sustained activation of the renin-angiotensin system increases blood pressure sufficiently to restore nephron perfusion. Thus, depending upon the availability of volume, renal perfusion and sodium balance can be restored either by volume retention or by increased angiotensin II (ANGII) formation and peripheral vasoconstriction. Similarities exist between 1-K, 1-C HT and low-renin essential hypertension (LRHT). In both cases, renal-pressure natriuresis is shifted to higher levels and there are marked increases in preglomerular resistance that necessitate increased MAP to maintain sodium balance. However, in 1-K, 1-C HT, there is a parallel shift of pressure natriuresis with little or no change in the slope of this curve, similar to that found in the normal-renin essential hypertension. In LRHT the slope of pressure natriuresis is decreased, indicating that blood pressure is much more salt sensitive than normal. Another difference is that PRA is low compared to normal PRA in 1-K, 1-C HT after compensatory increases in MAP. There is also no indication of glomerular membrane damage in 1-K, 1-C HT, whereas LRHT may have significant glomerulopathy, especially as hypertension progresses. These differences suggest that there may be additional factors besides preglomerular vasoconstriction involved in the etiology of LRHT. One possible factor is a reduction in nephron number in LRHT. Decreased functional nephrons would lead to glomerular hyperfiltration and increased distal tubular flow rate in the remaining nephrons, causing decreased PRA and eventually glomerular damage. Increased fractional sodium reabsorption, particularly in distal tubular segments, could also contribute to decreased PRA and cause blood pressure to be salt sensitive. These abnormalities, along with preglomerular vasoconstriction, may explain many of the characteristics of LRHT.
Animals↗
The hemodynamic response to chronic hyperinsulinemia in conscious dogs.
This study describes the hemodynamic effects of chronic hyperinsulinemia in seven normal dogs. Insulin infused at 1 mU/kg/min together with glucose at 14 mg/kg/min for 7 days increased fasting plasma insulin concentration approximately six-fold. Plasma glucose concentration was unchanged on day 1 but was below control on day 6. Mean arterial pressure decreased from 81 +/- 4 mm Hg to 70 +/- 3 mm Hg, while cardiac output increased to 30 +/- 8% above control by day 7. Total peripheral resistance decreased to 69 +/- 5% of control. Urinary sodium excretion was significantly decreased and was accompanied by a 22% increase in extracellular fluid volume with no change in blood volume. All parameters returned to control levels during the recovery period. These data suggest that, in addition to promoting renal sodium retention, insulin may lower blood pressure and increase cardiac output through a peripheral vasodilatory effect.
Animals↗
Parasitization of humans in West Virginia by Ixodes cookei (Acari: Ixodidae), a potential vector of Lyme borreliosis.
In 32 collections, two larvae, 33 nymphs, and one adult female Ixodes cookei Packard were collected from humans in West Virginia from August 1987 to May 1990. Most were attached. The ticks were found in 14 counties and were the most abundant Ixodes found biting humans. One nymphal I. cookei was removed from the left axilla of a 39-yr-old woman who lives and works in Monongalia and Marion counties, W. Va. The bite was the center of an expanding erythematous lesion reaching 4 cm in diameter, clearing centrally, and typical of erythema migrans. This association and the near absence of Ixodes dammini Spielman, Clifford, Piesman & Corwin from the state suggests the possibility that I. cookei may be an important vector of Lyme borreliosis in West Virginia. In five separate collections, five nymphal Ixodes dentatus Marx were removed from humans in four counties, implicating this species as a potential minor vector of Lyme borreliosis in West Virginia.
Adult↗
Current treatment approaches in the nonoperative and operative management of adolescent idiopathic scoliosis.
Idiopathic scoliosis is the most common type of lateral curvature of the spine, accounting for about 65% of adolescent patients with structural scoliosis. The treatment goal is to prevent moderate curves from becoming severe, because severe curves, in adults, may not only lead to serious medical and physical complications, but also cause significant cosmetic deformities. Fortunately, early detection, through school screening programs, has led to successful nonoperative management of idiopathic scoliosis. In those instances in which nonoperative management is not an option, surgical correction is available. Surgery prevents curve progression and offers the patient a significant correction of the cosmetic deformity. This article will review both treatment approaches in the management of adolescent idiopathic scoliosis.
Adolescent↗
Structure-activity relationships of pentamidine analogs against Giardia lamblia and correlation of antigiardial activity with DNA-binding affinity.
1,5-Di(4-amidinophenoxy)pentane (pentamidine) and 38 analogs of pentamidine were screened for in vitro activity against the enteric protozoan Giardia lamblia WB (ATCC 30957). All compounds were active against G. lamblia as measured by a [methyl-3H]thymidine incorporation assay. Antigiardial activity varied widely, with 50% inhibitory concentrations (IC50s) ranging from 0.51 +/- 0.13 microM (mean +/- standard deviation) for the most active compound to over 100.0 microM for the least active compounds. The IC50 of the most potent antigiardial agent, 1,3-di(4-amidino-2-methoxyphenoxy)propane compared favorably with the IC50s of the compounds currently used to treat giardiasis, i.e., furazolidone (1.0 +/- 0.03 microM), metronidazole (2.1 +/- 0.80 microM), quinacrine HCl (0.03 +/- 0.02 microM), and tinidazole (0.78 +/- 0.48 microM). A mode of antigiardial activity for these compounds was suggested by the correlation observed between antigiardial activity and the binding of the compounds to calf thymus DNA and poly(dA).poly(dT).
Animals↗
Inhibition of Cryptosporidium parvum in neonatal Hsd:(ICR)BR Swiss miceby polyether ionophores and aromatic amidines.
Cryptosporidicidal effects of two polyether ionophores (maduramicin and alborixin), a fluorinated 4-quinolone (enrofloxacin), and three analogs of pentamidine were evaluated in a suckling mouse bioassay. Treatment with all compounds except enrofloxacin and one of the pentamidine analogs [1,3-di(4-imidazolinophenoxy)propane] resulted in significant (P less than 0.05) reductions in oocyst excretion.
4-Quinolones↗
Activity of pentamidine and pentamidine analogs against Toxoplasma gondii in cell cultures.
The capabilities of pentamidine and nine pentamidine analogs to inhibit the development of Toxoplasma gondii were examined in vitro. Treatment of infected cultures with pentamidine and five of its analogs caused a significant (P less than 0.05) reduction in the numbers of tachyzoites produced. Analogs of pentamidine may be useful agents in the treatment of toxoplasmosis.
Animals↗
Sustained hyperinsulinemia increases arterial pressure in conscious rats.
A large body of correlational evidence relating plasma insulin levels and arterial pressure in obese hypertensives suggests that hyperinsulinemia may play a causal role in the development of hypertension in these subjects. However, experimental evidence supporting the ability of increased plasma insulin per se to increase blood pressure is lacking. The goal of this study was to determine the effect of hyperinsulinemia on mean arterial pressure and renal electrolyte excretion in eight conscious rats. Arterial pressure was determined by sampling the signal from an abdominal aortic catheter once per minute, 19 h/day by computer. A 5-day intravenous insulin and glucose infusion that increased plasma insulin concentration 43% significantly increased mean arterial pressure from 93 +/- 1 mmHg to an average of 101 +/- 2 mmHg for the 5-day experimental period. Heart rate increased from 369 +/- 8 to 406 +/- 3 beats/min. Urinary sodium excretion transiently decreased on day 1 of insulin, but no significant sodium retention was measured after 5 days of insulin infusion, suggesting that the blood pressure increase was not volume mediated. There were no changes in any of these variables in eight vehicle-infused rats. These results suggest that hyperinsulinemia can increase mean arterial pressure in conscious rats, but the underlying mechanism remains to be elucidated.
Animals↗
Chronic intrarenal hyperinsulinemia does not cause hypertension.
Hyperinsulinemia has been postulated to link obesity and hypertension via the antinatriuretic actions of insulin. The main goal of this study was to quantitate the importance of the direct intrarenal actions of insulin, independent of systemic effects, in altering blood pressure and renal function. This was accomplished by determining the responses to chronic intrarenal insulin infusion in uninephrectomized, chronically instrumented conscious dogs maintained on a 74 meq/day sodium intake. Insulin was infused at rates calculated to raise intrarenal, but not systemic, insulin to levels similar to those observed in obese hypertensive dogs. Intrarenal insulin infusion (0.6 mU.kg-1.min-1) for 7 days caused transient decreases in sodium excretion but no significant changes in potassium excretion. Mean arterial pressure did not change during 7 days of insulin infusion, averaging 93 +/- 4 mmHg during control and 93 +/- 3 mmHg during insulin infusion. Intrarenal insulin caused small increases in GFR but no significant changes in effective renal plasma flow or renal vascular resistance. These results demonstrate that insulin causes transient decreases in sodium excretion, but chronic intrarenal hyperinsulinemia does not elevate blood pressure in normal dogs. Additional factors other than the direct sodium-retaining effects of insulin may be important in raising blood pressure in obesity-associated hypertension.
Animals↗
Treatment effects of separate commitment laws for mental illness and chemical dependency.
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Adult↗
Variable tolerance of the developing follicle and corpus luteum to gonadotropin-releasing hormone antagonist-induced gonadotropin withdrawal in the human.
To examine the differential sensitivity of the ovary to temporary withdrawal of gonadotropin support at different stages of folliculogenesis and corpus luteum function, GnRH antagonist blockade of gonadotropin secretion was examined in 17 studies using the Nal-Glu GnRH antagonist. A vehicle control, antagonist treatment, and follow-up cycle format was used in each study. A previously determined ED100 dose of the Nal-Glu GnRH antagonist (150 micrograms/kg) or vehicle was administered sc every 24 h for 3 consecutive days in the midfollicular phase (MFP), late follicular phase (LFP), and midluteal phase (MLP). In studies in the MFP (n = 7), the largest follicle was 11 +/- 2 mm (mean +/- SEM), and the mean estradiol (E2) level was 220 +/- 44 pmol/L on the first day of antagonist administration. Administration of the antagonist resulted in a 75 +/- 6% suppression of LH (P less than 0.005), no significant change in FSH, and suppression of E2 to the assay detection limit (P less than 0.05). Total cycle length was increased compared to that of the vehicle control cycle (37.3 +/- 1.3 vs. 26.3 +/- 1.1 days; (P less than 0.005) due to prolongation of follicular phase length (P less than 0.005) and reinitiation of folliculogenesis. In the LFP (n = 5), the largest follicle was 16 +/- 1 mm (P less than 0.05 vs. MFP), and the E2 level was 394 +/- 95 pmol/L (P less than 0.05 vs. MFP) on the first day of antagonist administration. Antagonist administration resulted in a 65 +/- 6% suppression of LH (P less than 0.05), a 47 +/- 11% decrease in FSH (P less than 0.05), and no significant change in E2. Total cycle length was prolonged (32.4 +/- 2.2 vs. 25.6 +/- 0.4 days; P less than 0.05) due to an increase in follicular phase length (P less than 0.02); however, the prolongation of the follicular phase was significantly less than that of the MFP (8.0 +/- 1.5 vs. 15.1 +/- 0.1 days; P less than 0.001), suggesting ovulation from the initial dominant follicle. In studies in the MLP (n = 5), LH, E2, and progesterone decreased to the assay detection limit after antagonist administration, while FSH decreased by 36 +/- 4% (P less than 0.05). Menstrual bleeding occurred within 24-48 h of the final Nal-Glu antagonist injection.(ABSTRACT TRUNCATED AT 400 WORDS)
Adult↗
The renin-angiotensin system: renal actions and blood pressure regulation.
The RAS is part of an extremely powerful feedback system for long-term control of blood pressure and volume homeostasis. Disturbances that tend to lower blood pressure, such as heart failure, cirrhosis, and peripheral vasodilation, cause sodium and water retention until blood pressure returns to normal due, in large part, to the combined actions of ANGII and reduced arterial pressure. In response to increased sodium intake, decreased ANGII formation greatly amplifies the effectiveness of pressure natriuresis, thereby preventing large increases in body fluid volumes and blood pressure. In circumstances in which the RAS is inappropriately activated, the sodium retaining effects of ANGII necessitate increased blood pressure to maintain sodium balance via pressure natriuresis. Because the RAS is so powerful in regulating blood pressure, blockade of the system with ACE inhibitors offers a powerful therapeutic tool in diseases such as hypertension and congestive heart failure. The control of sodium excretion and blood pressure by ANGII is exerted through multiple intrarenal as well as extrarenal effects, including stimulation of aldosterone secretion, which can influence renal excretion. Current evidence suggests that the intrarenal effects of ANGII are quantitatively more important than those mediated by aldosterone in controlling blood pressure and renal excretion. The most important intrarenal effects of ANGII include efferent arteriolar constriction as well as direct effects on sodium transport. The constrictor effect on efferent arterioles also is important in preventing reductions in GFR in circumstances associated with impaired renal perfusion. Therefore blockade of ANGII formation in circumstances such as renal artery stenosis may caused marked reductions in GFR. However, in many patients efferent arteriolar vasodilation caused by ANGII blockade may not lower GFR markedly because of other autoregulatory mechanisms that compensate by causing parallel reductions in afferent arteriolar resistance. In these individuals, chronic ACE inhibition may prove to be beneficial in slowing the progression of renal disease because a reduction in glomerular hydrostatic pressure may help to prevent glomerular damage.
Aldosterone↗
Development of a radioligand receptor assay for measuring follitropin in serum: application to premature ovarian failure.
We have developed a radioligand receptor assay (RRA) with sufficient sensitivity and specificity for quantifying follitropin (FSH) in unextracted serum samples. Standard curves prepared by adding pituitary FSH to either buffer or gonadotropin-free serum were parallel and statistically indistinguishable in this assay, whereas gonadotropin-free serum alone had no activity. Cross-reactivity with related pituitary hormones was negligible. Pituitary FSH was calibrated with commonly used reference preparations so that RRA results could be compared with RIA results for identical standards. The patterns in daily blood samples in six normal menstrual cycles were similar by both methods. The mean RIA:RIA ratio in both the follicular and luteal phases was between 0.6 and 0.7, and at mid-cycle decreased to 0.48, suggesting an alteration of isohormone composition at mid-cycle. In 27 women with premature ovarian failure, RRA:RIA ratios ranged from below the RRA minimum detectable dose to 4.6, suggesting that immunoreactive FSH might not be capable of binding to the FSH receptor in some patients, whereas in patients with high RRA:RIA ratios, circulating inhibitors of FSH receptor binding might be present and perhaps contributing to the observed ovarian failure. Use of this RRA in conjunction with RIA and in vitro bioassays may better define the relative contribution of FSH isohormones, autocrine or paracrine modulators of FSH bioactivity, and FSH-receptor binding competitors to the "total FSH biological signal" as detected by the gonadal FSH receptor.
Adult↗