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Biomedical subjects

D L Kaiser

Publications and source records attributed to D L Kaiser.

At least 73 records · Page 4Linked to original sources

Steady-state response of conscious man to small expiratory resistive loads.

To determine the predominant steady-state ventilatory responses to mild expiratory flow-resistive loads, we subjected 14 normal subjects to expiratory resistances of 0-10 cm H2O/L/sec (R0-R3). Breathing patterns and abdominal muscle activity (EMG) were recorded during quiet breathing, and when ventilation was augmented by dead space breathing (7 subjects) or treadmill walking (7 subjects). Expiratory loading increased expiratory time (TE), tidal volume and mean inspiratory flow rate, while decreasing inspiratory duty cycle and respiratory frequency. Minute ventilation (VI) remained constant. These load responses were most prominent during quiet breathing, and were attenuated or abolished as VI increased. Abdominal EMG was negligible during quiet breathing, increased when VI increased, but showed no consistent response to R1-R3. Thus, the principal defense against mild expiratory loads is prolongation of expiration, accompanied by enhanced inspiratory drive. Abdominal muscle expiratory activity is elicited by increasing ventilation, but occurs only sporadically with expiratory loading of the magnitude studied.

Abdominal Muscles↗

Incidence of 24-hour faculty coverage in teaching EDs.

There is growing concern in academic emergency medicine as to the appropriateness of 24-hour faculty coverage in the teaching emergency department. We surveyed 170 teaching emergency departments, 49 of which had approved emergency medicine residencies, asking for information regarding 24-hour faculty coverage. We were able to separate each department into one of 15 profiles based on the two variables of average ED yearly census and hospital type. Seventy-three percent of university teaching hospital EDs and 65% of those with emergency medicine residencies have 24-hour faculty coverage; 83% of private teaching hospital EDs and 100% of those with emergency medicine residencies have 24-hour faculty coverage; and 79% of city/county teaching hospital EDs and 80% of those with emergency medicine residencies have 24-hour faculty coverage.

Emergency Medicine↗

Effects of long-term therapy with naltrexone on body weight in obesity.

The endogenous opiate system is thought to be associated with the regulation of food intake and body weight. Opiate antagonists decrease food intake in animals, but there are no controlled studies in obese man to evaluate body weight response to naltrexone. Sixty obese people were randomized into three groups and given 0, 50, or 100 mg of the opiate antagonist naltrexone for 8 weeks in an outpatient, double-blind study. Weight loss was not significant in either the 50 or 100 mg groups as compared with placebo. However, when broken down by sex, women had a significant (P less than 0.05) weight loss of 1.7 kg, while men did not lose weight. Side effects were modest, but six subjects had one or more abnormal liver function test results; in one subject these abnormalities appeared to be clinically significant. The effects of naltrexone on weight loss were less than expected in light of prior animal studies, but further studies with a wider dose range of naltrexone may be indicated.

Administration, Oral↗

Effects of calorie restriction and weight loss on glucose and insulin levels in obese humans.

The relative contributions of weight loss vs calorie restriction in the improvement of glucose tolerance in obese subjects has not been well studied. We measured fasting and stimulated glucose and insulin levels in seven obese subjects at 4 time periods: on a regular diet before weight loss, on a very low calorie ketogenic diet (VLCKD) after 4 days and after 6 weeks, and after 4 days back on a regular diet. Fasting glucose and insulin levels fell significantly after only 4 days of calorie restriction and did not change after 6 weeks. With return to a regular diet, these levels rose toward baseline even through body weight remained well below baseline. Stimulated glucose and insulin levels during an insulin tolerance test, intravenous glucose tolerance test, and standard meal demonstrated a similar pattern, although the changes due to either diet or weight loss were minimal. We conclude that calorie restriction has a greater effect on glucose and insulin levels than does weight loss in obese subjects who are losing weight.

Adult↗

Factors affecting immediate and long-term survival after emergent and elective splanchnic-systemic shunts.

The course of 121 shunted cirrhotic patients, managed according to a prospective protocol over a period of 10 years, was analyzed to determine predictors of 30-day and long-term survival. Forty-five per cent of the patients underwent emergent decompression within 12 hours of active bleeding, and 34% of the shunts were selective. Logistic regression linked early mortality to bilirubin and blood-urea nitrogen (BUN) (p = 0.001), and long-term survival to the presence of preoperative ascites and higher levels of alkaline phosphatase (p = 0.027), but neither variable set was a more accurate predictor than Child Class. Emergency shunt patients had greater risk of early death, 44% vs. 17% for patients shunted electively (p = 0.001), but beyond 30 days, their Kaplan-Meier survival curves were identical. Independently, angiographic prograde portal flow was favorably associated with short-term (p = 0.003) but not prolonged survival. The presence of Mallory bodies, fatty metamorphosis, and acute periportal inflammation, alone or in combination, had no prognostic value. Continued post-operative alcohol ingestion jeopardized long-term survival (p = 0.017). Survival of nonalcoholics was enhanced by selective as opposed to total splanchnic decompression (p = 0.009).

Adolescent↗

Bile duct carcinoma. Diagnosis and treatment.

Fifty-three patients were evaluated for carcinoma of the extrahepatic bile ducts at the University of Virginia from 1951 to April 1984. This population was retrospectively reviewed and 33 preoperative and postoperative variables were analyzed to evaluate the predictors of increased survival. No preoperative data, including symptoms, admitting laboratory data, or tumor location, predicted increased survival. Whipple resection yielded a median survival of 12 months; palliative resections, 1.5 months; and laparotomy, only 5.5 months; these differences were not statistically significant. Experience with six patients treated with internal radiation (iridium-192), plus as much as 4000 rads of external beam irradiation, suggests that this combination of radiation treatment may aid palliation.

Adenoma, Bile Duct↗

Can success in the surgical residency be predicted from preresidency evaluation?

Sixty-two residents entered the general surgical residency over a 10-year period, and 42 completed it. When the 20 who were dismissed from the program were compared by discriminant analysis to those who completed it successfully, it was found that Alpha Omega Alpha (AOA) membership, high class rank, clinical honors, and publications predicted success with 89% accuracy. Ten of the 42 who completed the program were rated as outstanding, 22 were average and 10 below average. No subjective or objective preresidency selection data correlated with later chief resident performance.

Educational Measurement↗

Effects of in vivo gonadal hormone environment on in vitro hGRF-40-stimulated GH release.

The effects of gender and the gonadal hormone environment on basal and stimulated growth hormone (GH) release by dispersed and continuously perifused rat anterior pituitary cells were examined. Cells from intact male and diestrus day 2 female rats and from castrate male rats either untreated or treated with testosterone (T) or 17 beta-estradiol (E2) were used. Basal GH release (ng/min per 10(7) cells; mean +/- SE) by cells from diestrus day 2 female rats was less than by cells from castrate rats treated with T (4.3 +/- 0.6 vs. 11.4 +/- 2.7, respectively; P less than 0.025). No other differences in basal release were detected. Concentration-response relationships were documented between human GH-releasing factor 40 (hGRF-40; 0.03-100 nM given as 2.5-min pulses every 27.5 min) and GH release. Mean (+/- SE) overall GH release (ng/min per 10(7) cells) above base line was greater by cells from intact male rats (496 +/- 92) than by cells from castrate (203 +/- 37.3; P less than 0.0001), castrate and T-treated (348 +/- 52.8; P = 0.008), or castrate and E2-treated (58.1 +/- 6.8; P less than 0.001) male rats or by diestrus day 2 rats (68.6 +/- 9.5; P = 0.0001).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Effects of acute uninephrectomy and age on renal blood flow autoregulation in the rat.

We previously showed that renal autoregulatory behavior is modified by both normal and compensatory renal growth. To determine whether the hemodynamic changes precede an increase in renal mass, the relationship of renal blood flow (RBF) to renal perfusion pressure (RPP) was examined in the remaining kidney of anesthetized young and adult rats 30 min following contralateral nephrectomy. In young control animals 32-41 days old, an autoregulation factor (AF) of 0.37 +/- 0.10 (SE) over RPP 70-100 mmHg indicates efficient autoregulation and did not change during the experiment. Acute uninephrectomy in young hydropenic rats resulted in a 16% increase in RBF at normal RPP, and AF increased to 1.22 +/- 0.34 for RPP 70-100 mmHg, reflecting marked impairment of autoregulation. In young animals in which saline infusion was not reduced at the time of uninephrectomy, RBF increased 22% at normal RPP, and autoregulation was similarly impaired (AF 0.92 +/- 0.12 for RPP 70-100 mmHg). Acute uninephrectomy in adult rats resulted in a 13% increase in RBF, with better preservation of AF (0.48 +/- 0.09) over the adult autoregulatory range (RPP 100-130 mmHg). These findings indicate that profound hemodynamic changes take place in the remaining kidney within 30 min of acute uninephrectomy and that they are qualitatively similar to those observed after compensatory hypertrophy has developed.

Aging↗

Comparison of indices used to detect hypoventilation during sleep.

Because there is no uniform method of measuring the severity of sleep apnea, we compared respiratory indices calculated from airflow and oxyhemoglobin saturation (SaO2) signals in 16 subjects during a night's sleep. Airflow was measured with a loosely fitting pneumotachograph or thermister and the following indices calculated manually: total apneas (A) and hypopneas (H); A and H per hour of sleep; total A H time; average duration of A H episodes, and A H index (the product of 2 and 4). SaO2 was measured with a Hewlett-Packard ear oximeter and the following indices calculated with a microcomputer; total number of desaturation (D) episodes; D episodes per hour of sleep; average maximum D; D index (the product of 7 and 8); SaO2 50 (1), and SaO2 10(1). There was a significant correlation among all indices; the highest correlation was between total A and H and total D (r = 0.97). We conclude that SaO2 indices calculated with a microcomputer correlate well with flow indices.

Humans↗

Pulsatile growth hormone secretion in normal man during a continuous 24-hour infusion of human growth hormone releasing factor (1-40). Evidence for intermittent somatostatin secretion.

Growth hormone (GH) secretory patterns were studied in a patient with ectopic growth hormone releasing factor (GRF) secretion and in normal men given continuous infusions of human growth hormone releasing factor (1-40)-OH (hGRF-40). In the patient with ectopic GRF secretion, GH secretion was pulsatile despite continuously elevated immunoreactive GRF levels. To determine if pulsatile GH secretion is maintained in normal subjects, we administered to six healthy young men vehicle or hGRF-40, 2 ng/kg per min, for 24 h and gave a supramaximal intravenous bolus dose of hGRF-40, 3.3 micrograms/kg, after 23.5 h of infusion. hGRF-40 infusion resulted in greater GH secretion than did vehicle infusion and pulsatile GH secretion was maintained throughout hGRF-40 infusion. During the 23.5 h of vehicle infusion, total GH secretion (microgram; mean +/- SEM) was 634 +/- 151 compared with 1,576 +/- 284 during hGRF-40 infusion (P = 0.042). The GH response to the intravenous bolus of hGRF-40 was greater after vehicle infusion than after hGRF-40 infusion; 877 +/- 170 and 386 +/- 125 micrograms of GH was secreted after the bolus on vehicle and hGRF-40 days, respectively (P = 0.015). The total amount of GH secreted during the 25.5 h of the two study days was not different; 1,504 +/- 260 and 1,952 +/- 383 micrograms were secreted during vehicle and hGRF-40 days, respectively (P = 0.36). Not only was pulsatile GH secretion maintained during hGRF-40 infusion, but there was augmentation of naturally occurring GH pulses, which is in contrast to the effect of gonadotropin-releasing hormone on gonadotropin secretion. We suggest that GH pulses are a result of GRF secretion that is associated with a diminution or withdrawal of somatostatin secretion.

Acromegaly↗

Enumeration of lactotropes and somatotropes among male and female pituitary cells in culture: evidence in favor of a mammosomatotrope subpopulation in the rat.

The hemolytic plaque assay technique can be used to detect specific hormone release from single pituitary cells. Using antisera raised against murine GH or rat PRL, we have enumerated the active lactotropes and somatotropes from male and female rat pituitary glands. These studies reveal sex-related differences in the number of cells exporting GH and PRL among anterior pituitary cells in culture. In the presence of human GH-releasing factor (hGRF), the mean percentage of GH cells was 53% in males and 30% in females (P less than 0.005). The mean percentage of PRL cells was 15% in males and 39% in females (P less than 0.008). These values were not significantly altered when hGRF was omitted. The sum of GH and PRL cells identified in separate plaque assays significantly exceeds the number obtained when GH and PRL cells were determined concurrently with a simultaneous plaque assay for both hormones. This difference is dependent on the presence of hGRF, since there was no difference when hGRF was omitted. These data identify the mammosomatotrope in numbers lower than previous reports. By this approach, the mammosomatotrope subpopulation numbers about 5% of all cells in culture. In summary, we demonstrate a sex-related difference in the number of cells exporting GH or PRL among pituitary cells in culture. This difference corresponds with and may underly sex-related differences in the responsiveness of GH and PRL secretion from the pituitary gland. Furthermore, a minor subpopulation of normal pituitary cells appears capable of simultaneous secretion of both GH and PRL.

Animals↗

Divergent influences of the structurally dissimilar calcium entry blockers, diltiazem and verapamil, on thyrotropin- and gonadotropin-releasing hormone-stimulated anterior pituitary hormone secretion in man.

We have tested the influence of a new calcium ion channel antagonist, diltiazem, on hypothalamic releasing hormone-stimulated secretion of LH and other anterior pituitary hormones in man. To this end, six normal men received a continuous infusion of GnRH (1 microgram/min) and TRH (2 micrograms/min) for 3 h under three different experimental conditions: 1) saline (control) infusion; 2) iv diltiazem (0.3 mg/kg bolus dose, and 0.002 mg/kg . min) infusion for 4 h beginning 1 h before releasing hormone injection; and 3) oral diltiazem (60 mg, every 6 h) administration for 1 week before pituitary stimulation. Blood was sampled at 10-min intervals for the subsequent immunoassay of LH, FSH, TSH, PRL, and GH concentrations and at hourly intervals for the assay of plasma diltiazem concentrations by high performance liquid chromatography. Despite sustained plasma diltiazem concentrations of 80-120 ng/ml during either iv or oral drug administration, the GnRH/TRH-stimulated release of LH, FSH, TSH, and PRL or the basal secretion of GH did not differ significantly from that during saline infusion. In contrast, when these subjects underwent the same infusion schedule using a structurally dissimilar calcium influx blocker, verapamil (5-mg bolus dose and 15 mg/h, continuous infusion), there was significant suppression of the delayed component of GnRH/TRH-stimulated LH release, with simultaneous enhancement of PRL secretion. We conclude that exogenously stimulated anterior pituitary hormone secretion in man exhibits differential susceptibility to the structurally discrete calcium entry blockers diltiazem and verapamil. Moreover, the differential influence of these two calcium ion channel antagonists on gonadotropes is distinct from that described in cardiac and smooth muscle cells.

Administration, Oral↗

Evidence for a limited growth hormone (GH)-releasing hormone (GHRH)-releasable quantity of GH: effects of 6-hour infusions of GHRH on GH secretion in normal man.

Human GH-releasing hormone [hGHRH-40 (GHRH)] stimulates GH release in a dose-dependent fashion when administered as single iv bolus doses or as continuous 90-min infusions. However, there has been variability in the GH responses, and it appears that there are waxing and waning effects of GHRH. To address whether these are a result of the dose of GHRH, time, or intermittent changes in sensitivity of the somatotrophs, we administered 6-h infusions of vehicle and different doses of GHRH to six normal men. In addition, an iv bolus injection of GHRH was given after 5.5 h of infusion to evaluate residual GH secretory capacity. The subjects were given infusions of either vehicle or GHRH (1, 3.3, and 10 ng/kg X min), followed by an iv bolus injection of 3.3 micrograms/kg on four separate occasions. GHRH infusions stimulated GH secretion compared to basal secretion. The changes from basal GH secretion (mean +/- SEM) were 2.0 +/- 1.6, 4.6 +/- 1.5, 12.7 +/- 5.1, and 8.2 +/- 1.8 ng/ml X h during the vehicle and GHRH (1, 3.3, and 10 ng/kg X min) infusions, respectively. The changes from basal GH secretion for 2 h after the iv bolus dose (after 5.5 h of infusion) were 33.3 +/- 8.7, 22.4 +/- 3.8, 14.0 +/- 3.6, and 10.5 +/- 2.0 ng/ml X h on the vehicle and GHRH (1, 3.3, and 10 ng/kg X min) infusion days, respectively. The magnitude of the GH response was inversely related to the GHRH infusion dose. The total amount of GH released during the 7.5-h study periods was not different among the vehicle and 3 GHRH infusion days. Thus, it appears that a finite amount of GH is released by GHRH. There was variability in the degree of responsiveness to the continuous infusions of GHRH. Surges of GH release occurred during the GHRH infusions, which may be attributed to intermittent secretion of a GH inhibitor, such a somatostatin.

Adult↗

Effects of intravenous, subcutaneous, and intranasal administration of growth hormone (GH)-releasing hormone-40 on serum GH concentrations in normal men.

In addition to stimulating GH release in normal subjects, GH-releasing hormone-40 (GHRH-40) stimulates GH secretion in some adults and children with GH deficiency. Recognizing that GHRH-40 may have potential as a therapeutic agent for the treatment of GH deficiency, we examined the effects of iv, sc, and intranasal (in) GHRH-40 administration on GH secretion and measured the plasma levels of immunoreactive GHRH achieved after the administration of the peptide via these different routes. Normal men were given vehicle or GHRH-40 iv (0.003, 0.01, 0.03, and 0.1 micrograms/kg; n = 10), sc (1, 3.3, and 10 micrograms/kg; n = 8), or in (3, 10, 30, and 100 micrograms/kg; n = 5). No subject had any symptoms after administration of vehicle or GHRH-40. During the 2-h period after iv administration of GHRH-40, the maximal increment in serum GH levels above basal (nanograms per ml; mean +/- SD) after the 0.1 micrograms/kg dose was 15.5 +/- 10.4 compared to 2.4 +/- 4.1 after vehicle (P = 0.0017). During the 3-h period after sc administration, when compared to the maximal increment in serum GH above basal after vehicle alone (10.2 +/- 12.9), the maximal increments above basal in serum GH were increased after both the 3.3 micrograms/kg (26.2 +/- 23.1; P = 0.022) and 10 micrograms/kg (63.6 +/- 53.5; P = 0.0003) doses. During the 3-h period after in administration, when compared to the maximal increment in serum GH above basal after vehicle alone (2.8 +/- 6.4), the maximal increments above basal in GH were higher after both the 30 micrograms/kg (18.5 +/- 10.4; P = 0.0053) and 100 micrograms/kg (21.7 +/- 8.1; P = 0.0028) doses. In addition, significant dose-response relationships were documented between the maximal increments above basal in serum GH and GHRH-40 administered by all routes. The mean (+/- SEM) peak plasma level of IR-GHRH (nanograms per ml) achieved after administration of 10 micrograms/kg GHRH-40, iv, as reported previously (66.6 +/- 17.6), was approximately 60- and 500-fold higher than the mean levels in the current study after administration of the same dose sc (1.11 +/- 0.39) or in (0.14 +/- 0.02), respectively. In summary, although GHRH-40 stimulates GH release when administered iv, sc, or in, significantly higher doses were required using the sc and in routes to achieve responses comparable to those obtained with iv administration.

Administration, Intranasal↗

Carotid endarterectomy after a completed stroke: reduction in long-term neurologic deterioration.

The merit of carotid endarterectomy for patients who previously have sustained a completed stroke remains controversial. Between January 1976 and December 1983, 118 stroke patients with mild to severe permanent neurologic deficits were evaluated. Fifty-nine patients were managed nonoperatively and 59 operatively. Both cohorts were similar in age and sex distribution, incidence of hypertension (69%), diabetes mellitus (25%), and cardiac disease (39%). In the long-term follow-up (medical cohort average was 44.1 +/- 5.0 months; surgical cohort average, 41.8 +/- 3.7 months) the overall survival rate was comparable, that is, there were nine medical deaths and eight surgical deaths. However, there was a significant difference in the development of new neurologic deficits. Twelve of the 59 unoperated patients had new neurologic deficits and three patients died at 12, 36, and 48 months as a result of a recurrent stroke. New neurologic deficits developed in only two of the 59 surgical patients and there were no stroke-related deaths. When the cumulative probability of remaining free from recurrent deficits was examined in the surviving patients at 6 years, all of the patients in the operated group remained free from recurrent deficits, whereas only 58% of the patients in the unoperated group were free of new neurologic deficits (p = 0.02). These data suggest that stroke patients with fixed mild to moderate neurologic deficits and with carotid lesions may be protected from recurrent neurologic complications by carotid endarterectomy.

Aged↗

Effects of acute left anterior descending occlusion on regional myocardial blood flow and wall thickening in the presence of a circumflex stenosis in dogs.

In this study, 2 hypotheses were tested: (1) Myocardium supplied by a stenosed circumflex coronary artery (LC) does not demonstrate compensatory increases in regional blood flow and systolic thickening when the left anterior descending coronary artery (LAD) is acutely occluded. (2) Blood flow to myocardium in the distribution of an acutely occluded LAD is lower in the presence of a stenosed than in the presence of an unstenosed LC. Fifty-three open-chest, anesthetized dogs were studied. Regional coronary blood flow (8 to 10-mu microspheres) and wall thickening (sonomicrometer crystals) were measured before and after LAD occlusion in the presence of an unstenosed LC artery, and a moderate and severe LC stenosis. Acute LAD occlusion in the presence of an unstenosed LAD was not accompanied by a significant increase in regional blood flow to the remote LC bed; posterior myocardial wall thickening, however, increased from 0.22 +/- 0.02% to 0.24 +/- 0.02% (p = 0.04). In the presence of a moderate LC stenosis (gradient 29 +/- 1 mm Hg), LAD occlusion was associated with a 9% (p = 0.02) decrease in endocardial flow and an 11% decrease in the endocardial/epicardial flow ratio (p = 0.002). Transmural flow was unchanged and there was no compensatory increase in posterior wall thickening. In the presence of a more severe LC stenosis (gradient 49 +/- 1 mm Hg), central LC endocardial flow decreased by 32% (p = 0.0008) at the time of LAD occlusion. Similar alterations were noted in the peripheral LC region.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Relationship of pretreatment transurethral resection of the prostate to survival without distant metastases in patients treated with 125I-implantation for localized prostatic cancer.

The authors assessed the relationship between transurethral resection of the prostate (TURP) and the probability of survival without distant metastases (survival) in patients with clinically localized prostatic cancer. Fifty-eight patients with obstructive voiding symptoms who underwent TURP within 12 months before pelvic lymphadenectomy and 125I-implantation were compared with 131 patients who did not require TURP before implantation. None received other treatment for the tumor. The overall survivals for the two groups were not significantly different, P greater than 0.1. When stratified by tumor grade or the presence or absence of pelvic lymph node metastases, the survivals for the two groups were also similar, P = greater than 0.1. However, survival associated with Stage C tumors was greater in the No TURP than in the TURP group (P = 0.003), and survival associated with Stage C tumors was greater in the TURP than in the No TURP group (P = 0.005). These data fail to provide convincing evidence that transurethral resection of prostatic cancers has an unfavorable impact on disease progression.

Adenocarcinoma↗