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Biomedical subjects

R Gilbert

Publications and source records attributed to R Gilbert.

At least 73 records · Page 4Linked to original sources

Presence of avian pancreatic polypeptide-like immunoreactivity in catecholamine and methionine-enkephalin-containing neurones within the central nervous system.

Using single and double staining immunohistochemical procedures it has been demonstrated that an avian pancreatic polypeptide-like immunoreactivity (APP-LI) co-exists with catecholamines in neurones within the A1/A3, A2 and A6 (locus coeruleus) cell groups, and also with methionine-enkephalin in cell bodies of the sacral parasympathetic system. Axonal and terminal immunoreactivity was observed in axons and nerve terminals in particularly high density within the dorsal horn of the spinal cord and originated in part from intrinsic cell bodies. Intense terminal labelling was also found around sacral and caudal lumbar motor neurones, and thoracic lateral sympathetic column neurones. Immunoreactive material was present in fibres around neurones of the periaqueductal grey, caudal raphe and the locus coeruleus and in neurones in the arcuate nucleus.

Animals

Relationship of rib cage and abdomen motion to diaphragm function during quiet breathing.

Although rib cage (RC) and abdomen (Ab) motion is believed to reflect intercostal and diaphragm contributions to breathing, systematic investigations have failed to confirm this. We measured inspiratory changes in RC and Ab anterior-posterior diameter (delta RC and delta Ab) both corrected for volume equivalence (isovolume) and not corrected (isodistance, observed), and correlated these with simultaneous changes in gastric (delta Pab) and esophageal (delta Ppl) pressure: delta Pab - delta Ppl = delta Pdi, the change in transdiaphragmatic pressure. The delta Pab/delta Pdi was used as an index of the relative contribution of diaphragm motion to the breathing process. Relative abdomen motion was expressed as delta Ab/(delta Ab + delta RC). Isodistance and isovolume delta Ab/(delta Ab + delta RC) correlated, R = 0.69; observed abdomen motion overestimated abdomen-diaphragm contribution to tidal volume. Isodistance delta Ab/(delta Ab + delta RC) was less for women than men; isovolume delta Ab/(delta Ab + delta RC) was similar for the two sexes. Among individuals, isodistance delta Ab/(delta Ab + delta RC) correlated with delta Pab/delta Pdi (R = 0.73, P less than 0.001). Within a given individual, the mean R for seven subjects for delta Pab/delta Pdi vs delta Ab/(delta Ab + delta RC) was 0.90. We conclude that observed rib cage and abdomen motion reflects intercostal and diaphragm contributions to breathing; the correlation is better within a given subject than among individuals.

Abdomen

One minute oxygen uptake in peripheral ischemic vascular disease.

Six males, ages 31-58, with ischemic vascular disease of the lower extremities, underwent treadmill testing with measurement of oxygen uptake at 45-60 seconds of exercise (VO2-45-60) as the test score. Tests were performed at 41, 123 and 164 watts of power against gravity. Depressed values were found in five subjects with aortic, iliac or common femoral disease but normal values in a subject with narrowing of the left superficial femoral artery. Reconstructive surgery resulted in normal values in four subjects retested. In three of these a calculation was made of the increased volume of oxygen uptake during the first minute of exercise associated with postsurgical improvement. The average was 430 ml, a value high enough to suggest increased aerobic metabolism of exercising muscles.

Adult

Characterization of corticosterone-induced protein synthesis in hippocampal slices.

Corticosterone significantly increases the incorporation of [3H]leucine into specific cytosol protein(s) isolated from in vitro hippocampal slices prepared from adult male albino rats. The present study showed that in slices coincubated with glucocorticoid plus a protein synthesis inhibitor (1 mM-cycloheximide), no such enhancement of amino acid incorporation was observed, suggesting that the hormone acts in the hippocampus to increase de novo protein synthesis. Further experiments demonstrated that the steroid-induced protein synthesis was first detectable (+ 5.7%) following a 30-min exposure of slices to corticosterone; slices incubated for 1 or 2 h both showed a 12% increase in synthesis of the affected protein(s) when compared with controls. In an attempt to determine whether the glucocorticoid alteration of protein metabolism was receptor-mediated, hippocampal slices were also incubated with 10 nM-progesterone, a steroid known to compete for corticosterone binding to its cytosol receptor. Progesterone alone, which does not translocate cytoplasmic receptors to the nucleus, did not alter hippocampal protein metabolism and effectively blocked the induction by corticosterone of the 54K protein(s). These studies provide evidence that in the rat hippocampus corticosterone interacts with high-affinity steroid receptors to regulate the synthesis of specific protein(s).

Animals

Mixed venous CO2 tension during exercise.

A series of experiments was undertaken in a total of 95 adult subjects, of whom 25 had coronary artery disease, to evaluate the extrapolation (Defares) CO2 rebreathing method vs. the equilibrium (Collier) method for estimating mixed venous CO2 tension. Collier values were corrected for the downstream effect, whereas Defares values were uncorrected. Although the methods gave similar mean values in separate series with normal subjects walking on a treadmill set at 123 W for 3 min, Collier values had a coefficient of variation (CV) of 2.5% in duplicate determinations and Defares values had a CV of 4.5%. In paired comparisons Defares values averaged either higher or lower than Collier values depending on variations in technique and the analysis of Defares tracings. Collier values were essentially unaffected by the duration of the rebreathing period (10 vs. 15 s). The Collier technique appears to be superior for the exercise evaluation of cardiac output in healthy and diseased subjects when the goal is obtain values at 82 or 123 W in single test sessions.

Adult

Stability of the arterial/alveolar oxygen partial pressure ratio. Effects of low ventilation/perfusion regions.

The alveolar-arterial oxygen partial pressure difference (AaDO2) and the arterial/alveolar oxygen partial pressure ratio (a/APO2) were compared for stability when inspired oxygen concentration (FIO2) changed. The analysis was based on a three-compartment lung model and experimental results in 10 patients with respiratory failure receiving assisted ventilation. It was found that a/APO2 was more stable than AaDO2 and more useful for: (1) comparing gas exchange in patients receiving different levels of FIO2, (2) following gas exchange in the same patient as FIO2 is changed, and (3) estimating the PaO2 expected at a given level of FIO2 if blood gas data are available at another level. However, areas with low ventilation/perfusion (V/Q) ratios may cause sudden changes in a/PO2 at certain critical values of PAO2. Most stable is a/APO2 and, therefore, most useful at FIO2 levels greater than 0.3, and PaO2 levels less than 100 torr.

Adult

One- and three-minute exercise response in coronary artery disease.

Treadmill exercise responses of oxygen uptake (VO2), CO2 production (VCO2), and venoarterial CO2 difference (Cv-Ca), measured by CO2 rebreathing (Defares technique) at 1 and 3 min of exercise, were studied in two separate series of control (apparently healthy) and coronary artery disease (CAD) subjects. In the 1-min series there were 21 controls and 15 CAD subjects. In the 3-min series there were 21 controls and 18 CAD subjects. All were males, ages 30--60 yr, and the CAD subjects had histories of myocardial infarction. In both series VO2 at 1 min and power requirement (P ) = 1,000 (VO2-1-1,000) was estimated where P =weight (kg) X grade (fractional) X walking speed (m/min). In the 1-min series (P = 1,000) all measurements were made at 45--60 s in separate test runs. In the 3-min series P was 750 kg.m/min, VCO2 and VO2 were measured at 2.5--3 min exercise, and Cv-Ca was measured at 3--3.25 min in the same test run. Data indicate that the average cardiac output (Q) for control subjects was 15 l/min in both series with lower values for CAD subjects. At 1 min reduced Q was accompanied by reduced VO2 or VCO2 and increased Cv-Ca, whereas at 3 min reduced Q was accompanied by increased Cv-Ca.

Adult

Measurement of transdiaphragmatic pressure with a single gastric-esophageal probe.

A single gastric-esophageal probe, 5 mm in diam, with two transducers mounted near the tip has been used to measure transdiaphragmatic pressure in human subjects. The transducers are linear up to at least 200 cmH2O pressure and provide equal deflections for both positive and negative pressures. The method is shown to give results comparable to the standard procedure using two balloon-tipped catheters, one in the stomach and one in the esophagus.

Catheterization

Role of single-breath carbon monoxide-diffusing capacity in monitoring the pulmonary effects of bleomycin in germ cell tumor patients.

Serial pulmonary function tests including single-breath carbon monoxide-diffusing capacity (DLCO), forced vital capacity (FVC), and forced expiratory volume in 1 sec were performed in a relatively homogeneous group of male patients with germ cell tumors treated with vinblastine, bleomycin, and cis-diamminedichloroplatinum. Of the pulmonary function tests used, the DLCO was shown to be the most sensitive indicator of subclinical bleomycin pulmonary effects. Decreases in DLCO were both total dose and schedule dependent. Patients receiving their total dose of bleomycin at a rate of 25 +/- 2 (S.D.) units/week developed a linear decrease in DLCO with increasing total doses of bleomycin. Changes in FVC did not correlate with bleomycin total dose. Although both the mean DLCO and FVC decreased after completion of bleomycin therapy, the mean FVC returned to base-line levels rapidly, whereas the decrease in mean DLCO was persistent for several months. When routine volumetric tests (FVC and forced expiratory volume in 1 sec) and DLCO are used in a systematic manner, DLCO is the most sensitive indicator of the subclinical pulmonary effects of bleomycin in germ cell tumor patients treated with vinblastine, bleomycin, and cis-diamminedichloroplatinum.

Adult

Prospective study of controlled oxygen therapy. Poor prognosis of patients with asynchronous breathing.

Thirty-two patients were evaluated within 24 hours of admission for 36 episodes of acute respiratory failure (arterial oxygen pressure less than or equal to 50 mm Hg). Clinical data, spirometric determinations, blood gas analysis, and synchronization of chest (rib cage) and abdominal (diaphragmatic) breathing movements were studied. All patients were initially treated with controlled oxygen therapy. In 25 episodes the patients recovered without intubation (successes). In nine episodes the patients required intubation and assisted ventilation; two of these patients died. Two patients died without intubation. The 25 successful episodes were compared with the 11 requiring intubation or associated with death (failures). The breathing pattern proved to be the best single factor for predicting success or failure (77 percent correct prediction). The breathing pattern plus the arterial carbon dioxide tension on admission was the best two-factor guide (86 percent correct prediction). Patients with asynchronous breathing and severe hypercapnia are so unlikely to do well with a program of controlled oxygen therapy that preparations for intubation and assisted ventilation should be made on admission and such measures should be instituted at the first sign of deterioration.

Airway Obstruction

Effect of cardiac, pulmonary, and vascular disease on one-minute oxygen uptake.

A simplified method for estimation of one-minute oxygen uptake (VO2-1) during treadmill grade walking at vertical power requirements of 250, 750, and 1,000 kg-meters/min was devised, where power=weight (kg) X grade (fractional) X walking speed. All subjects were men. There were 29 controls, 34 subjects with coronary arterial disease (of whom 18 had had myocardial infarction), nine subjects with diffuse pulmonary disease, and four subjects with ischemic vascular disease. Abnormally reduced values for VO2-1 were related to these diseases and, more specifically, to a history of myocardial infarction and (in pulmonary subjects) to reduced single-breath diffusing capacity. Lowest values of VO2-1 for a group were found in ischemic vascular disease. Reduced response of VO2-1 may therefore be caused by central defects of oxygen transport.

Adult