Mean Decrement Research Articles

Postural studies in pulsatile ocular blood flow: II. Chronic open angle glaucoma.

The pulsatile ocular blood flow (POBF) has been recorded in 15 patients with chronic open angle glaucoma. Measurements were performed during regular treatment with timolol 0.25% eyedrops, two weeks after withdrawal of this treatment, and then a further two weeks after its reinstitution. Readings were taken with subjects in both the erect and supine positions by means of a pneumotonometric probe to measure intraocular pressure (IOP), linked to a Langham ocular blood flow system. Assumption of the supine posture was associated with a significant increase in IOP in all phases of the study. Treatment with timolol lowered the mean IOP in comparison with the untreated phase (-4.4 (SEM 0.6) mmHg, p less than 0.001) but had no effect on the postural change. A significant reduction in POBF was recorded on assumption of the supine posture (-66 (SEM 18) microliters/min, p less than 0.001), representing a mean decrement of 19%. However, there were no significant differences in POBF between treated and untreated phases of the study. Comparison of the values obtained in patients with glaucoma (COAG) after withdrawal of treatment with those in subjects with ocular hypertension revealed that there was no significant difference in intraocular pressure between the two groups. However, both POBF (-68 (SEM 29) microliters/min) and the pulse amplitude of the intraocular pressure (ocular pulse: -0.45 (SEM) 0.14 mmHg) were significantly lower in the COAG patients. Pulsatile ocular blood flow is significantly lower in patients with chronic open angle glaucoma. Furthermore, the POBF and the postural response of these patients is not improved by the use of topical timolol therapy.

Interaction of 17β-estradiol and progesterone production in human granulosa-luteal cells

The secretion of 17β-estradiol (E 2) and the effect of exogenous E 2 on progesterone (P) production by granulosa-luteal cells from 18 women attending an in vitro fertilization (IVF) program were studied. The cells were separated from follicular fluid and precultured in medium containing fetal calf serum. On the third day of culture E 2 (0.25–2.0 μg/ml) was added onto the cells and its effect on both hCG-stimulated and basal P production was measured. E 2 inhibited both basal and hCG-stimulated P production. 1 μg/ml of E 2 caused mean decrements of 55 and 56% in basal and hCG-stimulated P production, respectively. The maximal inhibition by E 2 occurred at 6 hours of incubation, but when the cells were allowed to react with E 2 for longer periods of time the effect became less significant and more variable. At 48 h no inhibition was observed. At 6 h E 2 (1.0 μg/ml) increased both basal and hCG-stimulated pregnenolone production by approx. 10-fold, suggesting that the supression of P production was due to inhibition of 3β-hydroxysteroid dehydrogenase. Exogenous androgen, 5-Androsten-3β-ol-17-one sulfate, dehydroepiandrosterone sulfate (DHEAS), in a dose-dependent manner increased granulosaluteal cell E 2 production. The maximal response was about 1000-fold above the E 2 production of unstimulated cells and was not affected by hCG. However, the maximal amount of E 2 produced was minor in comparison to exogenous doses required for the suppression of P production and did not have the inhibitory effect. It is concluded that the production of E 2 by granulosa-luteal cells is mainly regulated by the availability of androgen substrate, and that E 2 functions as a modulator of luteal P production.

Pooled Prolactin Measurements in the Evaluation of Short Children*

PRL secretion was determined in 63 children undergoing evaluation of GH status. Children were assigned to 1 of 3 groups based on GH studies: group 1, those with abnormal GH responses to provocative testing (n = 23); group 2, children with normal GH responses to provocative testing and mean 24-h GH concentrations below 2.5 micrograms/L (n = 14); or group 3, those with normal stimulated GH secretion and mean 24-h GH concentrations of 2.5 micrograms/L or more (n = 26). Serum PRL concentrations were measured in daytime (0800-1600 h), nighttime (2200-0600 h), and 24-h pools of serum specimens obtained every 20 min over a 24-h period. Mean (+/- SD) daytime (17.5 +/- 14.3 micrograms/L) and 24-h (19.2 +/- 13.0 micrograms/L) pool PRL concentrations were significantly higher in group 1 than in group 3 (daytime, 6.7 +/- 2.3; 24 h, 10.2 +/- 2.5 micrograms/L; P less than 0.01). Mean nighttime pool PRL concentrations did not differ among groups. Mean nighttime pool PRL values were significantly higher (P less than 0.01) than daytime pool values in group 3 (nighttime pool, 13.6 +/- 3.6 micrograms/L; night to day ratio, 2.2 +/- 1.0) and group 2 (16.8 +/- 9.0 micrograms/L; night to day ratio, 2.5 +/- 1.5), but not within group 1 (21.4 +/- 13.5 micrograms/L; night to day ratio, 1.4 +/- 0.5). The mean peak and increment in PRL concentrations after an iv bolus of insulin-TSH-LHRH were not different among groups. The mean decrement in serum PRL level after L-dopa ingestion was greater in group 1 than in group 3 (P less than 0.05). Two children in group 2 and 10 in group 1 had significantly elevated daytime pool PRL concentrations (greater than 11.3 micrograms/L; 2 SD above the mean value for group 3). Two additional children in group 2 and 2 in group 1 had elevated 24-h (greater than 15.2 micrograms/L) pool PRL concentrations. One child in group 2 and 3 in group 1 had low 24-h PRL concentrations (less than 5.2 micrograms/L; less than 2 SD below the mean of group 3). Fourteen of 20 children with elevated daytime and/or 24-h pool PRL levels or low 24-h pool PRL values had structural or radiation-associated insults to the hypothalamic-pituitary axis evident in the history or with brain-imaging techniques; 1 had microphallus with panhypopituitarism and 5 children had no structural abnormalities.(ABSTRACT TRUNCATED AT 400 WORDS)

Pulmonary function responses of young and older adults to mixtures of O3, NO2 and PAN.

The pulmonary function of 32 nonsmokers (eight men and eight women, 18-26 years of age; eight men and eight women, 51-76 years of age) was measured before and after two-hour exposures to (1) filtered air (FA), (2) 0.45 ppm ozone (O3), (3) 0.13 ppm peroxyacetyl nitrate + 0.45 ppm O3 (PAN/O3), (4) 0.60 ppm nitrogen dioxide + 0.45 ppm O3 (NO2/O3), and (5) 0.13 ppm PAN + 0.60 ppm NO2 + 0.45 ppm O3 (PAN/NO2/O3). Subjects alternated 20-minute periods of rest and exercise (ventilation = 25 L/min). Forced vital capacity (FVC) was measured pre-exposure and five-minutes after each exercise period. Forced expiratory volume in one sec (FEV1.0) and forced expiratory flow between 25 and 75 percent of FVC (FEF25-75%) were calculated from the FVC tests. Data were analyzed by 4-factor analysis of variance (sex, age, time period, exposure). The responses of men and women were similar. FA exposure induced no effects. The young subjects' decrements in FVC, FEV1.0 and FEF25-75% became significant (P less than 0.01) after the second exercise period of the O3, NO2/O3 and PAN/NO2/O3 exposures, while the PAN/O3 decrements were significant (P less than 0.01) after the first exercise period. Although PAN/O3 induced significant decrements earlier than the other conditions including O3, the mean pre- to post-exposure decrements for the four conditions including O3 were similar. In contrast, the older subjects had smaller and fewer significant decrements in pulmonary functions. They had significant mean decrements in FVC following the third exercise period of the NO2/O3 and PAN/NO2/O3 exposures, in FEV1.0 after the third exercise period of the PAN/O3 and NO2/O3 exposures, and in FEF 25-75% beginning after the second exercise period of the NO2/O3 exposure. The results suggest that older men and women are less responsive to O3 and mixtures of O3, NO2 and PAN than young men and women, and that O3 is responsible for the decrements observed in pulmonary function.

The combined use of insulin and sulfonylurea therapy in patients with non-insulin dependent diabetes mellitus.

This study was initiated in order to evaluate the clinical efficacy of glipizide treatment in 18 patients with non-insulin dependent diabetes mellitus in poor glycemic control with insulin. Insulin dose was kept constant, and various facets of carbohydrate and lipid metabolism were evaluated before and from 4-6 months after the addition of glipizide. The results indicated that fasting and post-prandial glucose concentration were significantly (P less than 0.001) reduced following glipizide treatment, associated with a commensurate fall in glycosylated hemoglobin concentration. The average fall in fasting plasma glucose concentration in the total patient group approximated 60 mg/dl, and the mean decrement in 8 of the 18 patients who had a fall of more than 70 mg/dl in fasting glucose was 93 mg/dl. These results demonstrate that the addition of glipizide to the treatment program of patients with non-insulin dependent diabetes mellitus poorly controlled on insulin can lead to substantial clinical benefit.

Treatment of Hyperthyroidism due to Inappropriate Secretion of Thyrotropin With the Somatostatin Analog SMS 201–995*

The management of hyperthyroidism due to inappropriate secretion of TSH (IST) includes agents that selectively suppress TSH hypersecretion both in patients with TSH-secreting tumor [neoplastic IST (nIST)] in whom pituitary surgery was unsuccessful and in those with selective pituitary resistance to thyroid hormone action [nonneoplastic IST (nnIST)]. Among such agents, somatostatin administration has proven to be effective in blocking TSH hypersecretion, but its short plasma half-life prevented its use in long term therapeutic trials. The recent availability of a potent and long-acting analog of somatostatin (SMS 201-995, Sandostatin) prompted us to study its effects on serum TSH, alpha-subunit, and free thyroid hormone (FT4 and FT3) concentrations in five patients with nIST and three patients with nnIST. During short term SMS 201-995 administration (100 micrograms, sc, three times daily for 5 days) both serum TSH and alpha-subunit levels decreased in all patients with nIST (mean decrements, -86% and -85%, respectively), with concomitant normalization of serum FT4 and FT3 concentrations. In the three patients with nnIST, this treatment lowered serum TSH levels less well (mean decrement, -47%), although serum FT4 and FT3 levels normalized in one patient. Chronic SMS 201-995 (100 micrograms, sc, every 12 h for 1-7 months) treatment in four hyperthyroid patients (two with nIST and two with nnIST) resulted in a steady euthyroid state in both patients with nIST, with restoration of normal visual fields in one patient. In contrast, in both patients with nnIST, escape occurred after 2 weeks of therapy. We conclude that SMS 201-995 administration is effective treatment for patients with nIST, able to suppress TSH hypersecretion from the adenomatous thyrotrophs and, consequently, to restore clinical and biochemical euthyroidism in such patients. On the contrary, the inhibitory effects of SMS 201-995 on TSH secretion in patients with nnIST are weaker and transient.

Effect of reducing atrial pressure on atrial natriuretic factor and vasoactive hormones in congestive heart failure secondary to ischemic and nonischemic dilated cardiomyopathy

The effect of an acute and sustained reduction in atrial pressure on atrial natriuretic factor (ANF) and vasoactive hormone secretion was studied in 9 patients with congestive heart failure (CHF). Intravenous nitroglycerin was titrated to reduce the pulmonary artery wedge pressure by 30 to 50% and maintain this reduction for 4 hours. After 60 minutes of nitroglycerin administration, the mean decrement in wedge pressure was 10.0 ± 1.7 (standard error) mm Hg (35%) and plasma ANF was 65.3 ± 13.9 pmol/liter (35%). The initial decrease, sustained reduction and later increase in plasma ANF levels closely paralleled the changes in pulmonary arterial wedge (r = 0.94, p < 0.0001) and right atrial pressures (r = 0.91, p < 0.0001) during and immediately after the nitroglycerin infusion. Plasma aldosterone and cortisol levels increased during the first 2 hours of the nitroglycerin infusion, but there was little change in plasma norepinephrine or plasma renin activity. Although levels were elevated in CHF, plasma ANF still responded rapidly to changes in atrial pressure. A sustained reduction in pressure produced a sustained reduction in ANF levels. These findings provide further support for a regulatory role of ANF, even in chronic CHF.

Effect of Direction and Rate of Change of Calcium on Parathyroid Hormone Secretion in Uraemia

We have studied the control of amino-terminal parathyroid hormone (PTH) secretion in haemodialysis patients in response to slow or fast calcium infusion and during acute hypocalcaemia. In nine patients, fast calcium infusion (0.4 mmol/kg bodyweight per hour) for 15 min increased ionised calcium and reduced PTH, with an initial t 1/2 of 12.8 min. After the infusion had ceased, calcium decreased steadily, and PTH increased, mean PTH reaching baseline values when calcium was still significantly greater than pre-infusion values. During slow calcium infusion for 2.5 h (0.1 mmol/kg bodyweight per hour), parathyroid suppression was evident at 15 min, when the calcium increment was only 0.03 mM. After 60 min, PTH did not decrease further despite progressive hypercalcaemia. Hypocalcaemic haemodialysis led to rapid increases in PTH. After 15 min, the mean calcium decrement was 0.09 mM (P less than 0.01) and the mean PTH increment was 283 pg/ml (P less than 0.01). The parathyroid response was maximal at 30 min, and did not increase subsequently, despite progressive hypocalcaemia for a further 90 min. During recovery from hypocalcaemia, PTH reduced and, despite comparable hypocalcaemia, PTH during periods of increasing calcium was always lower at a given calcium concentration than while calcium was decreasing. This influence of the direction of change of calcium was not seen during hypocalcaemia. The results showed that even in-advanced renal disease, the parathyroid glands are highly responsive to small initial increments (0.03 mM) and decrements (0.09 mM) in blood calcium, though less so to further perturbation of blood calcium.(ABSTRACT TRUNCATED AT 250 WORDS)

Effects of ambient ozone on respiratory function in healthy adults exercising outdoors.

The effect of exposure to ozone (O3) in ambient air on respiratory function was studied in 30 healthy adult nonsmokers engaged in a regular daily program of outdoor exercise in Tuxedo, NY during the summer of 1985. Each subject did the same exercise each day, but exercise intensity and duration varied widely between subjects, with minute ventilation ranging from 20 to 153 L and duration ranging from 15 to 55 min. Spirometry was performed immediately before and after each exercise period. O3 concentrations during exercise ranged from 21 to 124 parts per billion (ppb). All measured functional indexes showed significant (p less than 0.01) O3-associated mean decrements with FVC at -2.1 ml/ppb, FEV1 at -1.4 ml/ppb, PEFR at -9.2 ml/s/ppb, FEF25-75 at -6.0 ml/s/ppb, and FEV1/FVC at -0.038%/ppb. Mean decrements were smaller for 10 subjects with minute ventilations greater than 100 L than for 10 other subjects with minute ventilations between 60 and 100 L or for the 10 subjects with minute ventilations below 60 L. Overall, the functional decrements were similar in magnitude to those we have seen in children engaged in supervised recreational programs in summer camps. For 10 subjects with minute ventilations comparable to those used in controlled 1- and 2-h exposures to O3 in purified air in chambers (50 to 80 L), the effects were about twice as large as those reported for the chamber studies.(ABSTRACT TRUNCATED AT 250 WORDS)

CADMIUM FUME INHALATION AND EMPHYSEMA

Lung function and chest radiographs of 101 men who had worked for 1 or more years manufacturing copper-cadmium alloy were compared with those of a referent group matched for age, sex, and employment status. Cigarette consumption was similar in the two groups. The cadmium workers had an excess of abnormalities of lung function and of radiographic changes consistent with emphysema. Classification of the cadmium workers by exposure categories based on either estimated cumulative cadmium exposure or liver cadmium measured by neutron activation analysis showed that abnormalities of lung function were greatest in those with the highest cumulative cadmium exposure or liver cadmium. The difference in the transfer coefficient (KCO) between cadmium workers and referents increased linearly with increasing cumulative exposure without evidence for a threshold. The estimated mean decrement in KCO for a cadmium worker employed 5 or more years with a cumulative exposure of 2000 yr.μg.m-3 (exposure to the current UK control limit of 50 μg.m-3 for a working lifetime of 40 yr) lies between 0·05 and 0·3 mmol.min-1.kPa-1.l-1 (95% confidence interval). This decrement is consistent with the functional and radiological changes of emphysema observed in this group of workers.

The immediate effects of iohexol on coronary blood flow and myocardial function in vivo.

Radiographic techniques used to quantify coronary blood flow all require bolus injection of contrast material, which markedly alters the flow being measured. Newer nonionic contrast agents have been shown to have fewer adverse hemodynamic, inotropic, and rheologic effects compared with ionic media and it has been suggested that they might not substantially affect coronary blood flow. Six dogs were instrumented with electromagnetic flow probes and subendocardial ultrasonic crystals. Intracoronary injections of iohexol (300 mg/ml iodine) were administered to establish a relationship between the dose and rate of contrast injection and the effect on flow and regional myocardial function. Two and 4 ml volumes of iohexol were injected at 3 ml/sec; 4 ml volumes were administered at 1 and 4 ml/sec. The 2 and 4 ml volumes decreased coronary flow by a mean of 31% (p less than .01) and 77% (p less than .001). The 4 ml injection at 1 and 4 ml/sec 77% (p less than .001) and 69% (p less than .001). The magnitude of the fall in flow was directly related to the dose, and the rate at which the flow nadir was attained was directly related to the rate of injection. Decrements in fractional shortening were temporally delayed by several beats compared with the flow changes and showed mean decrements of 19% to 29%. The effects on regional myocardial function were independent of contrast volume. However, the degree of dysfunction was more profound with slower infusion rates, suggesting that prolongation of contrast-induced ischemia was a major modulating factor.(ABSTRACT TRUNCATED AT 250 WORDS)

The dawn phenomenon does not occur in normal elderly subjects.

To determine whether the dawn phenomenon occurs in normal elderly subjects and thus contributes to the progressive mild fasting hyperglycemia of aging, we examined the effect of physiological insulin levels on glucose disposal and hepatic glucose production (HGO) between 0530 and 0800 h, and 0930 and 1200 h. Paired euglycemic insulin clamp studies (8 mU/m2 X min) were performed on healthy old subjects (n = 5), employing [3H]glucose methodology to measure glucose production and disposal rates. Basal plasma insulin, GH, glucagon, and cortisol levels, and HGO and glucose disposal rates were similar before each study. Steady state plasma insulin values were slightly, but not significantly, lower during the dawn study [dawn: 20.3 +/- 1.1 (SE); control: 23.5 +/- 2.1 microU/ml, P = 0.08]. Insulin clearance rates were higher during the dawn study (dawn: 523 +/- 16; control: 430 +/- 19 ml/m2 X min, P less than 0.01). Maximum glucose disposal rates (dawn: 3.10 +/- 0.24; control: 3.03 +/- 0.23 mg/kg X min) and minimum HGO levels (dawn: 0.83 +/- 0.09; control: 0.62 +/- 0.03 mg/kg X min) were not significantly different in each part of the study. There was a significant decrease in plasma GH during the dawn (P less than 0.01, analysis of variance) but not the control studies. There was no difference in cortisol levels during the euglycemic clamp between the dawn and control studies. The mean decrement in glucagon during the insulin infusion was similar in each part of the study. We conclude that the dawn phenomenon does not occur in healthy elderly subjects despite an increase in insulin clearance during the dawn period.

Genetic variation in Drosophila melanogaster for the life‐shortening effects of random lighting regimes

AbstractA daily random light‐dark regime (RLD), in which the onset of the photophase occurred at a random time of the 24‐h day, significantly shortened the life span of adult Drosophila melanogaster in 8 out of 23 strains tested. For the eight sensitive strains, the mean percent decrement in LT50 ± SE was 11.2 ± 0.6 d; for ten resistant strains, the mean decrement was 5.1 ± 0.8 d; for the remaining 5 strains, which could not be unambiguously classified as sensitive to RLD, the mean decrement was 8.6 ± 1.1 d. Strains homozygous for whole chromosomes (either X or one of the two large autosomes) exhibited continuous variation for sensitivity to clock shifting. No chromosome accounted for a disproportionate share of the variation, suggesting a multigenic basis for this phenotype. The LT50 in a normal, constant light‐dark regime (CLD) ranged from 31.7 d to 65.3 d, with chromosome 2 contributing most heavily to this variation. The correlation between LT50 and percent decrement in LT50 was not significant (r = .23, df = 21, P &gt; .20). In most sensitive strains, RLD and CLD groups did not begin to differ in percent surviving until after .5 of CLD LT50; after this critical point, RLD animals started dying at an increased rate. RLD may be stressful by disrupting temporal organization of physiological processes immediately following phase shifts, during the period marked by transients in observed phase response.

Neurophysiologic studies of sensory gating in schizophrenia: Comparison of auditory and visual responses

Gating of visual and auditory evoked responses was assessed in chronic schizophrenic patients treated with neurolepti cdrugs. Middle latency components of the visual evoked response (N90-P130) were recorded at the occiput after flash stimulus. Possible inhibitory mechanisms of sensory gating were assessed in a conditioning-testing paradigm by measuring the change in amplitude of response to a second stimulus, relative to the response to the first stimulus. Simultaneous electrooculograms were recorded to detect contamination of recordings by eye movement. Neither schizophrenic patients nor normal control subjects demonstrated significant suppression of visual evoked responses in the conditioning-testing paradigm. These results differed markedly from similar measurements of a middle latency component of the auditory evoked response (P50) recorded using the same conditioning-testing paradigm in these subjects. Normal controls showed significant decrements of the P50 response to the second auditory stimulus (mean decrement over 80%), whereas schizophrenic patients failed to show a significant decrement (mean less than 40%). This finding for auditory evoked responses replicated previous studies of normal and schizophrenic subjects. Multiple conditioning stimuli were substituted for the single conditioning stimulus used previously in an attempt to enhance gating of auditory responses, but suppression of the P50 test response did not increase in either normals or schizophrenics.

Individual differences in sensitivity and tolerance to alcohol.

Abstract Human responses to alcohol—especially sensitivity and acute behavioral tolerance—are being studied within a behavioral genetic design involving comparisons of scores from monozygotic twins, dizygotic twins, nontwin siblings, and unrelated (adoptee) pairs reared in the same family from infancy. The planned genetic analyses must await completion of data collection. The present sample is, however, adequate for analyses of means and for some analyses of individual differences in responses. For most of the measures being used, we find the usual mean decrement in performance after alcohol dosing to 0.100 BAC, but individual differences in response to alcohol are large, and a few individuals actually improve in performance after dosing. Also, on two tests, Cancellation and Block Rotations, there is a significant mean improvement in performance immediately after dosing. As yet we do not have a satisfactory explanation for this phenomenon. On most but not all of the tests, performance improves after the i...

Heart rate modulates the disposition of neurally released norepinephrine in cardiac tissues.

We determined the effect of heart rate on the disposition of neurally released norepinephrine from the cardiac tissues in open-chest, anesthetized dogs with complete atrioventricular block. After injecting desipramine to block the neuronal uptake of norepinephrine, we stimulated the cardiac sympathetic nerves supramaximally for about 3 minutes at a mean frequency of 2.7 Hz. In one series of experiments, we allowed coronary sinus blood flow to change spontaneously in response to cardiac pacing and sympathetic stimulation. The mean coronary sinus blood flows just before cessation of sympathetic stimulation were 67.4 +/- 4.2 (SE) and 37.4 +/- 2.7 ml/min during pacing at a high (150/min) and a low (60/min) frequency, respectively. The mean norepinephrine overflow into the coronary sinus blood during steady state sympathetic stimulation was 45.0 +/- 14.2% greater during high frequency pacing than during low frequency pacing. After cessation of neural stimulation, the norepinephrine overflow decayed more rapidly during high frequency pacing than during low frequency pacing. This difference in decay rates was mainly ascribable to the difference in coronary blood flows. In a second series of experiments, we adjusted the coronary sinus blood flow during sympathetic stimulation so that the flows were not significantly different during pacing at the two frequencies. During the initial 30-second period, after cessation of sympathetic stimulation, the mean decrements of norepinephrine overflow were 95.9 +/- 21.4 and 59.2 +/- 17.3 ng/min at the high- and low-pacing frequencies, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Quantitative computed tomography for prediction of vertebral fracture risk

Vertebral trabecular mineral content and peripheral cortical bone mineral were measured in 94 female and 44 male osteoporotic patients and compared to vertebral mineral values obtained for 323 control subjects in a cross-sectional study. The rate of change of spinal trabecular mineral with age (measured by quantitative computed tomography) in control females averaged 1.2% per year from age 20 to 80, with an accelerated loss demonstrated at the menopause. Trabecular bone mass in male controls declined an average 0.72% per year. Female osteoporotics had a mean decrement of 48 mg cm −3 (39%) compared to age-matched controls, whereas males were decreased 66 mg cm −3 (50%). Radial cortical bone was correlated with spinal mineral in osteoporotics for both males ( r = 0.48) and females ( r = 0.62). Vertebral compression fractures or wedging was generally absent in patients with vertebral mineral values above 110 mg cm −3, whereas almost all patients with values below 65 mg cm −3 had fractures. Quantitative computed tomography for measurement of vertebral trabecular bone mineral density is useful for defining those patients in whom the risk of vertebral fracture is increased.

The effects of leaks in spirometers on measurements of pulmonary function. The implications for epidemiologic studies.

Although the effects of spirometric leaks on forced expiratory tracings have been noted in retrospect in epidemiologic studies, the present study was designed to examine the effects of leaks of known size on the tracings of subjects with varying degrees of airway obstruction. Such information is needed to assess the potential impact of spirometric leaks on epidemiologic studies using existing spirograms collected in the absence of spirometer leak tests. Spirometric leaks of 5 to 9, 22 to 30, 34 to 46, 69 to 97, and 150 to 190 ml/s were produced by drilling holes of five sizes into spirometer mouthpieces. Eight subjects were studied, of whom five had FEV1/FVC of 0.70 or greater ("normal"), and three had FEV1/FVC of less than 0.70 ("obstructed"). Although leaks of 34 to 46 ml/s or less were found to be invisible in the forced expiratory tracings, they caused statistically significant (p less than .05) FVC decrements in all eight subjects, with a mean decrement of -0.35 l in the normal subjects and -0.79 l in the obstructed subjects. In contrast, the 34 to 46 ml/s leaks caused no significant FEV1 decrements in seven of the eight subjects. Since marked FVC decrements occurred even with the smaller leaks, the FVC should not be analyzed in epidemiologic studies in the absence of frequent, documented leak tests. However, the present study indicates that the FEV1 may be robust enough for analysis if recorded in the presence of small spirometric leaks.

Defect in the sodium-modulated tissue responsiveness to angiotensin II in essential hypertension.

In normal subjects, dietary sodium intake modulates renovascular, adrenal, and pressor responses to infused angiotensin II (AII). To examine the hypothesis that this modulation is abnormal in some patients with essential hypertension, we studied 18 hypertensives and 9 normal subjects twice--during dietary sodium restriction and during loading. Paraaminohippurate (PAH) clearance was used to assess renal plasma flow. AII was infused in graded doses (0.3-3.0 ng/kg per min). Plasma aldosterone, cortisol, renin activity, AII, sodium, potassium, and PAH clearance were measured at the onset and end of each AII dose. During dietary sodium repletion, eight of the subjects with essential hypertension showed a normal renovascular response (greater than 125 ml/min per 1.73 m2) to AII infusion (3 ng/kg per min). The decrement in renal blood flow in these normal responders (NR) was 168 +/- 10, which was comparable to the range in normotensive subjects (206 +/- 25 ml/min per 1.73 m2). All of the remaining hypertensive patients, designated abnormal responders (AbR), had lower (less than 125) renal blood flow responses to the same dose of infused AII (mean decrement: 84 +/- 11 ml/min per 1.73 m2) compared with the NR and normotensive subjects. Renal blood flow responses to all AII doses were statistically greater on a high-vs.-low salt diet in the NR (P less than 0.001, chi-square) and normotensives (P = 0.004, chi-square) but sodium intake had no effect on this response in the AbR. Basal renal blood flow in NR increased significantly (P less than 0.001, paired t test) with dietary sodium repletion, from 491 +/- 36 (low salt) to 602 +/- 40 ml/min per 1.73 m2 (high salt), but was almost identical in the AbR on differing dietary sodium intakes (429 +/- 24 vs. 425 +/- 26 ml/min per 1.73 m2). The adrenal responses to sodium intake and infused AII also differed in the two subgroups. In the NR, the adrenal response to AII was significantly greater (P = 0.011, Wilcoxon signed rank test) after sodium restriction. In contrast, there was no significant difference in the aldosterone response to AII infusion between the low and high sodium diets in the AbR. Thus, a substantial subgroup of essential hypertensives has an abnormality in responsiveness to AII in two systems central to volume homeostasis: the kidney and adrenal. They fail to modulate their renal blood flow and aldosterone responses to AII with changes in dietary sodium intake. Moreover, basal renal blood flow does not increase appropriately with increased sodium intake. These abnormalities, which may be due to an increased local production of AII or a defect in the AII receptors in these three target tissues, could contribute to the elevated blood pressure.

Control of upper gastrointestinal bleeding with a microcrystalline collagen hemostat.

A microcrystalline collagen hemostat (MCH) widely used in general surgery was tested in the control of bleeding from experimentally produced gastric ulcers. Five dogs had a gastrotomy and were given heparin. Using the standard "ulcer maker," three sets of three ulcers were made in the gastric mucosa of each animal. Blood from each ulcer was collected for a 5-min period to allow for stabilization of bleeding. MCH powder or slurry or no MCH was placed directly on one ulcer of each set in random order. The bleeding rate for the next 10 min was measured. Mean decrements in the bleeding rate for slurry MCH and dry MCH-treated ulcers were 87% and 81%, respectively, compared with 51% for controls, P less than 0.05. Twelve MCH-treated ulcers, but no control ulcer, stopped bleeding completely, P less than 0.01. Preliminary observations show that MCH slurry can be applied through an endoscope and may be hemostatically effective in man. MCH may have a role in the endoscopic control of gastrointestinal bleeding.