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Biomedical subjects

A H Morris

Publications and source records attributed to A H Morris.

At least 19 recordsLinked to original sources

Comparison of in vivo and in vitro Hahn T2 measurements in rat lung.

We compared in vivo and in vitro Hahn echo T2 measurements in rat lungs in both imaging and nonimaging modes. All measurements could be characterized by multiexponential functions consisting of either two or three exponentials. Essentially the same values of the time constants were observed for spontaneously breathing rats and for excised lungs.

Animals

A successful computerized protocol for clinical management of pressure control inverse ratio ventilation in ARDS patients.

We have developed a computerized protocol that provides a systematic approach for management of pressure control-inverse ratio ventilation (PCIRV). The protocols were used for 1,466 h in ten around-the-clock PCIRV evaluations on seven patients with severe adult respiratory distress syndrome (ARDS). Patient therapy was controlled by protocol 95 percent of the time (1,396 of 1,466 h) and 90 percent of the protocol instructions (1,937 of 2,158) were followed by the clinical staff. Of the 221 protocol instructions, 88 (39 percent) not followed were due to invalid PEEPi measurements. Compared with preceding values during CPPV, the expired minute ventilation was reduced by 27 percent during PCIRV while maintaining a pH that was not clinically different (mean difference in pH = 0.02). There was no difference in the PaO2, PEEPi, or the FIO2 between PCIRV and CPPV. The PEEP setting was reduced by 33 percent from 9 +/- 0.05 to 6 +/- 0.6 and the I:E ratio increased from 0.64 +/- 0.04 to 2.3 +/- 0.10. Peak airway pressure was reduced by 24 percent (from 59 +/- 1.5 to 45 +/- 0.6) and mean airway pressure increased by 27 percent (from 22 +/- 0.8 to 28 +/- 0.6) in PCIRV. Right atrial and pulmonary artery pressures were higher and cardiac output lower in PCIRV but blood pressure was unchanged. The success of this protocol has demonstrated the feasibility of using PEEPi as a primary control variable for oxygenation. This computerized PCIRV protocol should make the future use of PCIRV less mystifying, simpler, and more systematic.

Adult

Growth hormone therapy in hypophosphatemic rickets.

The effects of growth hormone therapy on the biochemical measures of bone metabolism were studied in 11 children aged 3.5 to 17 years who had familial hypophosphatemic rickets; five were male. Subjects were maintained on a regimen of stable doses of conventional therapy (calcitriol and phosphate). Subjects were studied at baseline receiving conventional therapy and during three sequential treatment periods: no therapy (4 weeks), growth hormone only (0.05 mg/kg per day for 4 weeks), and conventional therapy plus growth hormone (2 weeks). The nine youngest subjects were continued on a regimen of triple therapy for an additional 24 weeks. Serum phosphate averaged 0.93 +/- 0.13 mmol/L (mean +/- SD) at entry and decreased when the subjects were not receiving any therapy. During the 4 weeks of growth hormone only treatment, phosphate rose in all 11 subjects (0.70 +/- 0.08 mmol/L to 0.83 +/- 0.08 mmol/L). With triple therapy, phosphate remained higher than with no therapy. Calcitriol, osteocalcin, and parathyroid hormone increased as the subjects received growth hormone alone. Insulinlike growth factor I z scores rose significantly in response to growth hormone therapy alone. All nine subjects receiving 6 months of triple therapy increased their growth rate z scores. Exogenous growth hormone therapy may be useful in familial hypophosphatemic rickets.

Adolescent

Retinal blood flow following a tyramine-induced increase in blood pressure.

The effect of increasing systemic blood pressure on retinal blood flow was investigated in anaesthetised miniature pigs. Blood pressure was increased by the infusion of the sympathomimetic amine, tyramine. Volume flow was determined from axial erythrocyte velocity, measured by laser Doppler velocimetry, and vessel diameter, measured from monochromatic retinal photographs. Measurements were taken when mean arterial pressures were elevated by a mean of 22 +/- 3% and 50 +/- 8% above resting values, which represented increases of 31 +/- 2% and 74 +/- 16% in ocular perfusion pressures. Retinal blood flow increased by 8.5 +/- 8% at the lower infusion rate and by 57 +/- 19% at the higher infusion rate. We conclude that tyramine infusion is a suitable method for the study of retinal autoregulation and that the upper limit of retinal autoregulation in miniature pigs lies between 22-50% above resting mean arterial pressure.

Animals

Alveolar air-tissue interface and nuclear magnetic resonance behavior of lung.

Inflated lungs are characterized by a short nuclear magnetic resonance (NMR) free induction decay (rapid disappearance of NMR signal), likely due to internal (tissue-induced) magnetic field inhomogeneity produced by the alveolar air-tissue interface. This phenomenon can also be detected using temporally symmetric and asymmetric NMR spin-echo sequences; these sequences generate a pair of NMR images from which a difference signal (delta) is obtained (reflecting the signal from lung water experiencing the air-tissue interface effect). We measured delta in normal excised rat lungs at inflation pressures of 0-30 cmH2O for asymmetry times (a) of 1-6 ms. Delta was low in degassed lungs and increased markedly with alveolar opening when measured at a = 6 ms (delta 6 ms); delta 6 ms varied little during the rest of the inflation-deflation cycle. Delta 1 ms (a = 1 ms) did not vary significantly on inflation and deflation. Measurements of delta at a = 3 and 5 ms generally lay between those of delta 1 ms and delta 6 ms. These findings, which are consistent with theoretical predictions, suggest that measurements of delta at appropriate asymmetry times are particularly sensitive to alveolar opening and may provide a means of distinguishing alveolar recruitment from alveolar distension in the pressure-volume behavior of the lung.

Air

Increased survival of ARDS patients with severe hypoxemia (ECMO criteria).

The adult respiratory distress syndrome (ARDS) is a form of diffuse lung injury associated with multiple risk factors. Patients with severe hypoxemia who meet blood gas criteria defined by the extracorporeal membrane oxygenation trial (ECMO) of 1974 to 1977 have a reported survival of 11 percent. The reported survival has remained unchanged for 15 years despite numerous technologic advances. We prospectively studied ARDS patients who met ECMO blood gas criteria. One hundred seventy-eight ARDS patients were prospectively screened over a 30-month period. Fifty-one of these patients met ECMO blood gas criteria and 23 (45 percent) survived (p less than 0.001 vs ECMO trial). No obvious differences in etiology, APACHE II score, organ system failure, or the incidence of sepsis was found between survivors and nonsurvivors. We conclude that survival of ARDS patients who met ECMO blood gas criteria in our institution is higher than that previously reported from both other centers and our own hospital.

Adult

Open lung biopsy does not correlate with pulmonary function after the adult respiratory distress syndrome.

Abnormalities of pulmonary function occur following the adult respiratory distress syndrome (ARDS). To determine if open lung biopsy (OLB) during ARDS predicts late pulmonary function abnormalities, we examined nine survivors of ARDS who had OLB during ARDS. Open lung biopsy was performed within two weeks of the diagnosis of ARDS, and the following were scored by a pulmonary pathologist as to extent and severity: hyaline membranes (HM), interstitial fibrosis (IF), air space organization (AO), interstitial cellularity (IC), and type 2 cell proliferation (T2C). Pulmonary function tests performed at least one year after ARDS were also used for analysis. Percent predicted Dco, TLC, DL/VA, and FVC were regressed against extent, severity, and combined scores. No significant correlation was found despite impressive histologic abnormalities. These data suggest that the severity and extent of HM, IF, AO, T2C, or IC do not correlate with lung function following ARDS.

Female

In vivo demonstration of the Haldane effect during extracorporeal gas exchange.

During the extracorporeal support (LFPPV-ECCO2R) of 11 patients suffering from severe lung failure (ARDS), we consistently noticed a higher arterial than mixed-venous PCO2 in blood samples drawn at the same time. Two explanations are possible: a) the Haldane effect (HE), b) CO2 from lung tissue metabolism. In order to distinguish changes in PCO2 due to the HE from those due to tissue CO2 production, CO2 content (CCO2) was calculated. The results were compared to animal experiments with hyperoxic apnea, after which arterial and mixed-venous samples were drawn simultaneously. All blood gas samples were analyzed for pH, PCO2, PO2, and O2-saturation, from which CCO2 was calculated. In both groups, PaCO2 was 2.15 mmHg (2.7 mmHg respectively) higher at a lower CaCO2 (-2.87 ml/l, -14.9 ml/l). Oxygen saturation increased by 8.1% in the human group and 17.8% in the animal group. A significant relationship was found between changes in PCO2 and changes in O2-saturation. This is a demonstration of the Haldane effect.

Animals

A laser Doppler velocimetry study of the effect of hypoglycaemia on retinal blood flow in the minipig.

The effect of acute hypoglycaemia (plasma glucose less than 2.2 mmol/l) on retinal venous blood flow in the minipig has been determined using bidirectional laser Doppler velocimetry and red free retinal photography. In six pigs the mean flow in a retinal vein increased from 19.3 (+/- 2.8 SEM) microliters/min to 29.7 (+/- 7.5) microliters/min during hypoglycaemia (p less than 0.05) with a return to 18.6 (+/- 3.6) microliters/min when euglycaemia was restored. Retinal blood flow is affected by hypoglycaemia or its haemodynamic consequences.

Animals

Clinical evaluation of computer-based respiratory care algorithms.

A collection of computer-based respiratory care algorithms were implemented as a prototype computer-based patient advice system (COMPAS) within the existing HELP hospital information system. Detailed medical logic recommended ventilator adjustments for 5 different modes of ventilation: assist/control (A/C), intermittent mandatory ventilation (IMV), continuous positive airway pressure (CPAP), pressure controlled inverted ratio ventilation (PC-IRV), and extracorporeal carbon dioxide removal (ECCO2R). Suggestions for adjusting the mode of ventilation, fraction of inspired oxygen (FiO2), positive end-expiratory pressure (PEEP), peak inspiratory pressure, and several other therapeutic measures related to the treatment of severe arterial hypoxemia in adult respiratory distress syndrome (ARDS) patients were automatically presented to the clinical staff via bedside computer terminals. COMPAS was clinically evaluated for 624 hours of patient care on the first 5 ARDS patients in a randomized clinical trial. The clinical staff carried out 84% (320/379) of the computerized therapy suggestions. In response to a questionnaire distributed to clinical users of the system, 86% judged the system to be potentially valuable. Through implementation of COMPAS, a computer-based ventilatory therapy advice system, we have laid the groundwork for standardization of ventilator management of arterial hypoxemia in critically ill ARDS patients.

Algorithms

Regional effects of repetition time on NMR quantitation of water in normal and edematous lungs.

It is well known that pulmonary edema is, in general, spatially nonuniform. Since the NMR spin-lattice relaxation time (T1) is increased by lung edema, the spatial distribution of T1 will be nonuniform. When the repetition time (TR) is short relative to the T1 of edematous lung, lung water content will be underestimated and this underestimation will be spatially nonuniform as well. Therefore, technical artifacts which are a complex function of lung edema and its spatial distribution are expected. We compared overall and regional (topographic) lung water density measurements obtained from living rats (with normal or edematous lungs) using repetition times of 2.0 and 6.2 s (at a magnetic field of 1 T), to quantify this uneven T1 effect for normal and edematous lungs. NMR measurements at TR = 2.0 s underestimated whole lung water density (-rho H2O) TR = 6.2 s) by an average of 7.2% in normal rats and 22.5% in rats with pulmonary edema. Regional -rho H2O underestimation (%delta-rho H2O) varied from 2.2 to 8.8% (groups means) in normal lungs and from 7.3 to 30.8% in edematous lungs. As a result, the interquartile range (of the voxel distribution as a function of rho H2O) underestimated the spatial nonuniformity of lung water density by 28.0% in edematous lungs, likely because of greater loss of NMR signal from high-water-density, long-T1 lung regions. Both %delta-rho H2O and T1 were significantly correlated with -rho H2O at TR = 6.2 s.(ABSTRACT TRUNCATED AT 250 WORDS)

Body Water

Implementation of a computerized patient advice system using the HELP clinical information system.

A COMputerized Patient Advice System (COMPAS) was designed to test the feasibility of using the HELP clinical information system to direct the respiratory therapy of intensive care (ICU) patients acutely ill with adult respiratory distress syndrome. A modified black-board control architecture allowed the application of knowledge in either a forward or a backward chaining mode. Expert clinicians recommended decision logic and actions for five different modes of ventilatory support. The clinical staff used COMPAS to manage the ICU ventilatory support of five patients for a total of 624 hr. During that time there were 407 decision-making opportunities. COMPAS automatically generated therapy suggestions 379 (93.1%) times and the clinical staff accepted COMPAS's recommendation in 320 (84.4%) of these cases. These results suggest that the ventilatory support of severely ill ICU patients can be managed by a clinical information system using a blackboard control architecture.

Algorithms

Oregon's Patrick case and Supreme Court decision.

Does the Patrick decision affect properly done peer review used to consider quality patient care? The answer is most definitely no! If guidelines are followed that abide by the HCQIA and hospital peers review bylaws, then one can be fairly certain that physician reviewers are, indeed, immune to most liability challenges (one should remember, however, that compliance with HCQIA only provides immunity from federal and state law private claims, and not actions by the U.S. Department of Justice as a State Attorney General, i.e. criminal antitrust claims). We must be aware of and revise where necessary to conform to HCQIA our own hospital medical staff bylaws and policies as well as state procedural and reporting policies. We have learned that anticompetitive acts in the business of medicine are dealt with under the law no differently than anticompetitive acts in any other business. We must be aware of antitrust laws and remember as an extension of Patrick that medical groups dealing with alternative health delivery systems and joint ventures must consider any anticompetitive aspects of proposed contracts. Failure to do so could put us in jail.

Humans

Increased insulin-like growth factor I binding to red blood cells of normal prepubertal children.

Young children are growing at a time when circulating levels of IGF-I measured by RIA are generally less than or equal to values in nongrowing adults. 125I-Thr59-IGF-I binding to receptors on conveniently available red blood cells was studied in 33 normal adults (nine males, 24 females) and 13 normal prepubertal children aged 3-10 y (10 boys, three girls; all Tanner stage 1). Red blood cell specific binding of 125I-Thr59-IGF-I was determined by displacement of labeled Thr59-IGF-I by unlabeled Thr59-IGF-I or insulin in a dose-dependent manner. Mean (+/- SEM) 125I-Thr59-IGF-I specific binding was significantly higher (p = 0.01) in prepubertal children than in adults (13.9 +/- 0.7% versus 11.6 +/- 0.5%/3 x 10(9) cells/mL). Specific binding did not differ between adult males and females. There was no significant correlation between specific binding and reticulocyte count. Scatchard analysis demonstrated a linear plot. Increased binding to red blood cells in the prepubertal children appeared to be due to an increase in receptor affinity (Ka = 4.97 +/- 0.42 x 10(8) M-1 versus 3.70 +/- 0.41 x 10(8) M-1; children versus adults; p = 0.03). Mean receptor concentrations were not different in children and adults (64.4 +/- 8.5 versus 58.0 +/- 5.6 binding sites/cell). There was a significant positive correlation between 125I-Thr59-IGF-I specific binding and affinity (p = 0.007, r = 0.39). We speculate that the greater specific binding of labeled Thr59-IGF-I to red blood cells in prepubertal children may provide a mechanism for enhanced cellular responsiveness to relatively low levels of circulating IGF-I.

Adult

Absence of nonclassical congenital adrenal hyperplasia in patients with precocious adrenarche.

We studied 31 patients (28 girls and 3 boys), ranging in age from 3.2-7.9 yr, with precocious adrenarche defined by the presence of early sexual hair development, no signs of virilization, and bone age within +3 SD of the mean for chronological age. To determine if this symptom complex stemmed from any form of nonclassical (late-onset) congenital adrenal hyperplasia, an ACTH stimulation test was performed on each patient using a standard 0.25-mg dose of Cortrosyn, given as an iv bolus. Twelve pubertal children (7 girls and 5 boys) and 18 prepubertal children (11 girls and 7 boys) served as normal controls. Baseline and stimulated 17-hydroxypregnenolone (17-OHPreg), 17-hydroxyprogesterone, (17-OHP), 11-deoxycortisol, dehydroepiandrosterone, androstenedione, testosterone, and cortisol levels were measured. Using published nomogram standards for serum 17-OHP response to ACTH, no child with precocious adrenarche was diagnosed as having nonclassical 21-hydroxylase deficiency. Eight girls, however, had a stimulated 17-OHP value that exceeded the mean response for pubertal and prepubertal controls by more than +2 SD [range, 295-670 ng/dL (8.94-20.3 nmol/L)]. Stimulated 11-deoxycortisol values [less than 400 ng/dL (11.6 nmol/L)] ruled out any cases of nonclassical 11 beta-hydroxylase deficiency. No patient had nonclassical 3 beta-hydroxysteroid dehydrogenase deficiency, as defined by both the stimulated 17-OHPreg and the 17-OHPreg/17-OHP ratio to be more than +2 SD above the mean for pubertal children [1354 ng/dL (41.0 nmol/L) and 10.4, respectively]. In conclusion, we could not provide any biochemical evidence for nonclassical congenital adrenal hyperplasia in a large group of children with precocious adrenarche.

17-alpha-Hydroxypregnenolone