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Biomedical subjects

J E Hall

Publications and source records attributed to J E Hall.

At least 271 records · Page 15Linked to original sources

Differential regulation of luteinizing hormone, follicle-stimulating hormone, and free alpha-subunit secretion from the gonadotrope by gonadotropin-releasing hormone (GnRH): evidence from the use of two GnRH antagonists.

To examine the differential regulation of glycoprotein hormone secretion from the gonadotrope by GnRH, the Nal-Glu GnRH antagonist was administered to euthyroid women in the early follicular phase (days 1-5) of the menstrual cycle, and the results compared to previous studies with the Nal-Arg GnRH antagonist. After a 4-h period of baseline sampling at a frequency of every 10 min, a single sc dose of the GnRH antagonist was administered to each subject. Frequent sampling continued for 8 h, followed by hourly sampling for a further 16 h. LH, FSH, and free alpha-subunit were measured serially in assays with high specificity. There was a 90% concordance of LH and free alpha-subunit pulses during the baseline sampling period. Pulsatile secretion of LH and free alpha-subunit was immediately abolished at the highest dose of the Nal-Glu antagonist for at least 8 h. The maximum percent suppression of LH after administration of the Nal-Glu GnRH antagonist was 70 +/- 4%, 80 +/- 4%, and 83 +/- 1% at doses of 15, 50, and 150 micrograms/kg, respectively, compared to 51 +/- 10%, 70 +/- 5%, and 69 +/- 5% at doses of 50, 150, and 500 micrograms/kg Nal-Arg antagonist. Decreases in FSH were 28 +/- 2%, 32 +/- 7%, and 39 +/- 2%, with increasing doses of the Nal-Glu antagonist compared with 25 +/- 6%, 17 +/- 6%, and 28 +/- 4% reductions at increasing doses of the Nal-Arg antagonist. Free alpha-subunit decreased 22 +/- 4%, 23 +/- 4%, and 28 +/- 3% at increasing doses of the Nal-Glu antagonist and 12 +/- 4%, 27 +/- 4%, and 30 +/- 7% with increasing doses of the Nal-Arg antagonist. For the Nal-Glu antagonist, suppression of LH was greater than that of FSH and free alpha-subunit at all doses (P less than 0.001), while FSH suppression was greater than that of free alpha-subunit at the highest dose only (P less than 0.05). For the Nal-Arg antagonist, LH suppression was greater than that of FSH or free alpha-subunit at all doses (P greater than 0.01), and FSH suppression exceeded that of free alpha-subunit at the 50 micrograms/kg dose. Suppression of LH was greater with the Nal-Glu antagonist than with the Nal-Arg antagonist at doses of 50 and 150 micrograms/kg (P less than 0.05), and FSH suppression was greater with the Nal-Glu antagonist at 150 micrograms/kg (P less than 0.01), while the degrees of maximum suppression were similar for the two different GnRH antagonists for free alpha-subunit.(ABSTRACT TRUNCATED AT 400 WORDS)

Adult↗

Role of the renin-angiotensin system in control of sodium excretion and arterial pressure.

The RAS is part of an extremely powerful feedback system for long-term control of arterial pressure and volume homeostasis as illustrated in Figure 4. 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 renal perfusion pressure. In response to disturbances such as high sodium intake, suppression of ANGII greatly amplifies the effectiveness of the basic pressure natriuresis and diuresis mechanism, thereby preventing large increases in body fluid volumes and blood pressure. In circumstances in which the RAS is inappropriately activated, the sodium-water retaining effects of ANGII necessitate increased blood pressure to maintain sodium and water balance via pressure natriuresis. The sodium retaining actions of the RAS are mediated by intrarenal as well as extrarenal mechanisms. The intrarenal actions of ANGII include a direct effect on tubular sodium transport as well as a potent constrictor action on efferent arterioles which increases tubular reabsorption by altering peritubular capillary physical forces. The constrictor action of ANGII on efferent arterioles also plays an important role in stabilizing GFR and therefore in preventing fluctuations in excretion of metabolic waste products that depend upon a high GFR for excretion. ANGII is known to stimulate proximal reabsorption, but the effects on more distal tubular segments have not been completely elucidated. The primary extra-known to stimulate proximal reabsorption, but the effects on more distal tubular segments have not been completely elucidated. The primary extra-renal effect of ANGII which influences sodium excretion is stimulation of aldosterone secretion. Current evidence, however, suggests that the various intrarenal actions of ANGII are quantitatively more important in causing sodium retention than those mediated by changes in aldosterone secretion. However, the combined intrarenal and extrarenal actions of ANGII on sodium reabsorption provide the body with one of its most potent feedback systems for long-term regulation of body fluid volumes and arterial pressure.

Animals↗

[Transiliac leg lengthening: experiences with a modified Salter osteotomy].

Transiliac limb lengthening osteotomy is a modified Salter innominate osteotomy which uses a trapezoidal interposition bone graft instead of the usual triangular graft to achieve up to 3 cm of intrapelvic lengthening. It allows correction of certain forms of postural imbalance and pelvic obliquity, as well as allowing an optimal and variable amount of acetabular redirection. This review of 105 patients who have undergone the procedure at our institution revealed the following indications: decompensated scoliosis, 26 patients; acetabular dysplasia with ipsilateral femoral shortening, 34 patients; intrapelvic asymmetry, 7 patients; pure limb length inequality, 38 patients. Intrapelvic lengthening averaged 2.5 cm. Correction of decompensated scoliotic curves averaged 7 degrees reduction in Cobb angle. Improvement in center-edge angle in patients with hip dysplasia averaged 17 degrees. Reduction in size of shoe lift required to balance the trunk in all cases was correlated closely with the intrapelvic lengthening achieved. Complications included two transient neurapraxias (one femoral, one femoral and sciatic), two cases of sacroiliac subluxation (one patient with myelodysplasia, and one patient with polio), three cases of partial graft collapse, and six instances of broken fixation pins, and three deep wound infections. No patient had chondrolysis or avascular necrosis of the femoral head. After average follow-up of nearly 5 years (minimum follow-up 2 years), patients who underwent transiliac limb lengthening osteotomy for correction of postural imbalance for various causes retained satisfactory correction.

Adolescent↗

Posterior fusion for Scheuermann's kyphosis.

Ten patients with Scheuermann's kyphosis were surgically treated with posterior spine fusion and Harrington heavy compression-rod instrumentation. This procedure relieved pain and deformity in all ten patients. The average follow-up period was 26.6 months. The average curve before surgery was 71.4 degrees and at follow-up examination was 39.3 degrees. The postoperative correction of kyphosis averaged 32 degrees (45%), with an average loss of correction of 7.8 degrees. Posterior fusion with Harrington heavy compression-rod instrumentation may prove to be the procedure of choice in Scheuermann's kyphosis that is severe but flexible on hyperextension with a curve greater than 65 degrees.

Adolescent↗

Arthrodesis of the shoulder in children.

Ten children had an arthrodesis of the shoulder for a paralytic condition involving the muscles; nine of them were available for long-term follow-up. In the children who were eight to fifteen years old at the time of operation, the angle of arthrodesis was 45 degrees of abduction, 25 degrees of flexion, and 25 degrees of internal rotation. This angle allowed symptomless and useful function of the extremity. No patient had a stress fracture or discomfort when the arm was at rest at follow-up. An asymptomatic click in the acromioclavicular joint in one patient indicated that this may be a future site of abnormality. The children apparently accommodated easily to the arthrodesis of the shoulder. Neither self-image nor overall function seemed to be impaired by the operation. The over-all function postoperatively was related to the neurological integrity of the distal muscles.

Adolescent↗

Determination of luteal phase length by quantitative basal temperature methods: validation against the midcycle LH peak.

Basal temperature data are known to provide unreliable assessments of luteal phase length when they are evaluated by qualitative, visual-pattern methods. This study of 24 cycles in 24 women compared the serum LH peak day with the luteal phase onset day determined by three quantitative basal temperature methods: a) a new computerized least mean square method developed by the authors; b) the mean temperature method reported by Vollman; and c) a computerized version of the World Health Organization cumulative sum method of Royston. The luteal phase onset day determined by the three quantitative basal temperature methods, (a, b, and c) correlated well with the midcycle LH peak (r = 0.879, 0.891, and 0.791, respectively, all p less than 0.001). The cumulative sum method, however, was only able to analyze 19/24 cycles. The mean delay between the LH peak day and the luteal phase onset day determined by thermal shift was 2.4 +/- 1.5, 2.7 +/- 1.4, and 4.1 +/- 2.0 d (mean +/- SD), respectively. The mean temperature method, but not the other two methods, showed an increasing delay between the LH peak day and the thermal shift day with longer follicular phase lengths. Rectal and oral temperature data from the same cycle give identical luteal onset days when analyzed by the least mean square and mean temperature methods, but discrepant days by the cumulative sum analysis. The least mean square technique is a reliable and precise method for population documentation of luteal phase lengths.

Adult↗

High-performance liquid chromatographic method for the quantification of several diamidine compounds with potential chemotherapeutic value.

A high-performance liquid chromatographic method has been developed for the detection and quantification of pentamidine and pentamidine analogues of chemotherapeutic value in order to measure their concentration in physiological fluids. The compounds were extracted from urine over octadecyl solid-phase extraction columns, followed by chromatographic separation with an octadecyl reversed-phase column. For the mobile phase, a gradient of 31.5-37.5% acetonitrile in water, with sodium heptanesulfonate and tetramethylammonium chloride as ion modifiers, was used. This method was used to reliably detect levels as low as 341 ng/ml without concentration of the compounds during the solid-phase extraction. The assay was used to determine the effectiveness of several solid-phase extraction columns for isolating the compounds of interest and to quantify the amount of pentamidine and its analogues contained in the urine of dosed rats.

Animals↗

The structural organization and protein composition of lens fiber junctions.

The structural organization and protein composition of lens fiber junctions isolated from adult bovine and calf lenses were studied using combined electron microscopy, immunolocalization with monoclonal and polyclonal anti-MIP and anti-MP70 (two putative gap junction-forming proteins), and freeze-fracture and label-fracture methods. The major intrinsic protein of lens plasma membranes (MIP) was localized in single membranes and in an extensive network of junctions having flat and undulating surface topologies. In wavy junctions, polyclonal and monoclonal anti-MIPs labeled only the cytoplasmic surface of the convex membrane of the junction. Label-fracture experiments demonstrated that the convex membrane contained MIP arranged in tetragonal arrays 6-7 nm in unit cell dimension. The apposing concave membrane of the junction displayed fracture faces without intramembrane particles or pits. Therefore, wavy junctions are asymmetric structures composed of MIP crystals abutted against particle-free membranes. In thin junctions, anti-MIP labeled the cytoplasmic surfaces of both apposing membranes with varying degrees of asymmetry. In thin junctions, MIP was found organized in both small clusters and single membranes. These small clusters also abut against particle-free apposing membranes, probably in a staggered or checkerboard pattern. Thus, the structure of thin and wavy junctions differed only in the extent of crystallization of MIP, a property that can explain why this protein can produce two different antibody-labeling patterns. A conclusion of this study is that wavy and thin junctions do not contain coaxially aligned channels, and, in these junctions, MIP is unlikely to form gap junction-like channels. We suggest MIP may behave as an intercellular adhesion protein which can also act as a volume-regulating channel to collapse the lens extracellular space. Junctions constructed of MP70 have a wider overall thickness (18-20 nm) and are abundant in the cortical regions of the lens. A monoclonal antibody raised against this protein labeled these thicker junctions on the cytoplasmic surfaces of both apposing membranes. Thick junctions also contained isolated clusters of MIP inside the plaques of MP70. The role of thick junctions in lens physiology remains to be determined.

Animals↗

Does chronic hyperinsulinemia cause hypertension?

The aim of this study was to determine whether chronic hyperinsulinemia, comparable to that found in obesity-associated hypertension, causes sustained increases in mean arterial pressure (MAP) or potentiates the hypertensive effects of angiotensin II (ANG II). Insulin infusion (0.5 or 1.0 mU/kg/min, IV), with plasma glucose held constant by IV glucose infusion, for seven to 28 days raised plasma insulin by five- to ten-fold, but did not significantly change MAP in dogs with reduced kidney mass that were maintained on high sodium intake. In dogs infused with ANG II to cause mild hypertension, insulin for 28 days did not potentiate the hypertension. Insulin infusion did, however, cause modest sodium retention during the first few days of infusion. These findings suggest that additional factors besides hyperinsulinemia per se are responsible for obesity-associated hypertension.

Angiotensin II↗

The renin-angiotensin system. Normal physiology and changes in older hypertensives.

The long-term effects of angiotensin (ANGII) on arterial pressure regulation appear to be closely linked to volume homeostasis, via the renal-pressure natriuresis mechanism, both in normal humans and in older hypertensives. In response to disturbances such as increased sodium intake, suppression of ANGII and aldosterone formation greatly amplifies the effectiveness of the pressure natriuresis mechanism, thereby preventing large increases in body fluid volumes and minimizing the rise in blood pressure needed to maintain sodium balance. When ANGII levels are inappropriately elevated, the antinatriuretic effects of ANGII cause increased arterial pressure, which then serves to maintain sodium and water balance via the pressure natriuresis mechanism. The primary intrarenal and extrarenal mechanisms by which ANGII controls renal excretion and arterial pressure include: (1) a direct effect of ANGII on tubular sodium transport; (2) a preferential constrictor action of ANGII on efferent arterioles, which increases sodium reabsorption by altering peritubular capillary physical forces (efferent arteriolar constriction also prevents excessive decreases in glomerular filtration rate when renal perfusion is compromised, such as in renal artery stenosis); and (3) extrarenal effects of ANGII, including stimulation of aldosterone secretion. Current evidence suggests that the direct effects of ANGII on the kidney are quantitatively more important than indirect effects mediated by aldosterone. In older hypertensives, plasma renin activity and aldosterone concentration are often suppressed, perhaps due to loss of functional nephrons and increased sodium chloride delivery to the macula densa of the remaining nephrons.(ABSTRACT TRUNCATED AT 250 WORDS)

Aging↗

Atrial natriuretic peptide and pressure natriuresis: interactions with the renin-angiotensin system.

The aim of this study was to quantitate the effects of increases in atrial natriuretic peptide (ANP), within the pathophysiological range, on the acute pressure natriuresis mechanism and the role of the renin-angiotensin system (RAS) in modulating these effects. Renal hemodynamics and electrolyte excretion were measured in anesthetized dogs while renal perfusion pressure (RPP) was controlled at three levels (120-122, 100, and 75 mmHg) with and without intrarenal infusion of ANP at 5 ng.kg-1.min-1. Sodium excretion was significantly higher during ANP infusion at RPP of 122 +/- 3 mmHg, averaging 55.8 +/- 13.7 during control and 113.3 +/- 23.3 mueq/min during ANP infusion. AT RPP of 101 +/- 1 mmHg, sodium excretion was 51.8 +/- 17.4 during control and 93.0 +/- 17.6 mueq/min during ANP infusion, but at RPP of 75 +/- 0 mmHg there was no difference in sodium excretion between control and ANP infusion. In a second set of dogs, angiotensin II (ANG II) formation was blocked with captopril (20 micrograms.kg-1.min-1), circulating (5 ng.kg-1.min-1), and the above protocol was repeated. When the RAS was fixed, the renal responses to ANP infusion were abolished, even at the higher pressure levels. These data indicate that ANP increases the slope of pressure natriuresis; at higher levels of RPP, ANP potentiates pressure natriuresis but not at lower pressures. In addition, part of this effect may be due to suppression of the RAS, because the ANP-induced shift in the pressure natriuresis relationship was abolished when circulating ANG II was maintained constant.

Animals↗

Role of renal nerves in control of sodium excretion in chronic congestive heart failure.

The aim of this study was to examine the contribution of the renal nerves to the sodium retention in chronic congestive heart failure produced by rapid ventricular pacing. In 10 female dogs the left kidney was denervated and the urinary bladder was split to allow separate 24-h urine collection from an innervated and a denervated kidney in the same dog. The dogs were placed on an 80-meq/day sodium intake and permitted to recover for at least 2 wk. Control measurements were made for 5 days followed by ventricular pacing at 270-300 beats/min for 6 days. Cardiac output (CO), measured with an electromagnetic flow probe around the ascending aorta, fell from a control of 2.4 +/- 0.3 to 1.4 +/- 0.2 l/min (6 day average) during pacing while mean arterial pressure (MAP) fell from 91 +/- 4 to 71 +/- 3 mmHg. In six dogs, sodium excretion fell to an average of less than 2 meq/day (80 meq/day intake) during the 6-day pacing period in both the innervated and denervated kidneys. In four dogs, sodium excretion returned back toward control on days 3-6 of pacing despite sustained reductions in CO and MAP. However, there were no differences in renal hemodynamics or electrolyte excretion between innervated and denervated kidneys in either the compensated or decompensated dogs. These results suggest that other control mechanisms, besides the renal nerves, are primarily responsible for the sodium retention in this model of chronic congestive heart failure.

Aldosterone↗

Closed intravenous administration of gonadotropin-releasing hormone: safety of extended peripheral intravenous catheterization.

The use of pulsatile gonadotropin-releasing hormone is an effective means of inducing ovulation, but requires prolonged intravenous (IV) or subcutaneous administration. We hypothesized that the use of self-contained infusion pumps using fluids maintained in a closed system would permit safe peripheral IV administration of gonadotropin-releasing hormone, and possibly other hormones, over prolonged intervals. Thirty-eight female patients undergoing pulsatile IV gonadotropin-releasing hormone therapy were followed for 1958 catheter days (230 catheters). Catheters were removed for signs of local inflammation, at the completion of a treatment episode or, initially, at routine intervals of 7-10 days. There were no episodes of fever (temperature over 37.5C) and three episodes of local inflammation. The incidence of significant catheter-tip cultures was 11%, and none were associated with local inflammation. There were four positive blood cultures (2%), none associated with local or systemic signs of infection. We conclude that the use of a closed system of prolonged peripheral IV cannulation is relatively safe when combined with fastidious care of the catheter site and careful outpatient monitoring for long-term administration of pulsatile gonadotropin-releasing hormone.

Adult↗

Mycobacterium kansasii in a rhesus monkey.

The incidence of pulmonary disease caused by "atypical" mycobacteria has been increasing gradually in the human population since the 1950s. Mycobacterium kansasii and Mycobacterium intracellulare are the two organisms most responsible for this trend. A rhesus monkey was euthanatized and necropsied after reacting positive to mammalian Old Tuberculin on semi-annual testing. Histopathology demonstrated the presence of small numbers of acid fast organisms in pulmonary lesions. Further microbiological testing identified the causative organism as M. kansasii.

Animals↗

13C-NMR analysis of alanine metabolism by isolated perfused livers from C3HeB/FeJ mice infected with African trypanosomes.

1. Isolated perfused livers from mice infected with Trypanosoma brucei rhodesiense formed substantially more [3-13C]-lactate from [3-13C]-alanine than livers from uninfected mice. Quantities formed by infected livers increased as infection progressed. 2. Infected livers produced more 13C-labeled glutamate and glutamine, with label scrambled between C-2 and C-3. Scrambling also produced [2,3-13C]-aspartate, [2-13C]-alanine and [2-13C]-lactate. Delayed appearance of label in C-4 of glutamate/glutamine in infected livers reflects significant endogenous stores of unlabeled acetyl CoA. 3. Although differences do exist in catabolism of [3-13C]-alanine by perfused livers from infected and control mice, trypanosomiasis does not cause permanent breakdown or blockage of hepatic alanine metabolism.

Alanine↗