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Biomedical subjects

M L Ryan

Publications and source records attributed to M L Ryan.

At least 19 recordsLinked to original sources

Superior mesenteric artery and renal artery blood flow velocity measurements in neonates: technique and interobserver reliability.

The objective of this study was to establish the interobserver reliability for superior mesenteric artery (SMA) and renal artery (RA) Doppler blood flow velocity (BFV) measurements in neonates. Forty-two clinically stable infants were enrolled, mean (SD) gestational age 33 (2) weeks, birthweight 2.00 (0.54) kg, postnatal age 10 (11) days. Doppler recordings were made by two trained observers. The SMA and RA were studied with a 5.0-MHz phased array transducer. The optimal spectral trace from each artery containing a minimum of five consecutive waveforms was analysed. The peak systolic velocity (PS), end diastolic velocity (ED) and mean peak velocity (MV) were measured and the time-averaged mean velocity (TAV) and waveform indices were calculated. Using the intraclass correlation coefficient (ICC) the estimates of interobserver reliability for different measurements varied from 0.40 to 0.83. Substantial agreement was obtained between observers in the TAV, PS, ED and MV; the ICC varied from 0.72 to 0.83 demonstrating that Doppler BFV measurements of the SMA and RA are reliable in neonates.

Blood Flow Velocity

Effects of carotid body sympathetic denervation on ventilatory acclimatization to hypoxia in the goat.

Our objective was to test the hypothesis that diminishing sympathetic input to the carotid body (CB) during prolonged exposure to hypoxia results in increased CB afferent activity and increased ventilatory drive. Six awake goats were studied prior to and following sectioning of the efferent sympathetic input to the CB from the superior cervical ganglion. Ventilatory responses to acute and prolonged isocapnic hypoxia (PaO2 40 Torr) and drugs (norepinephrine and dopamine, 0.5, 1.0 and 5.0 micrograms.kg-1 min-1) were collected prior to the denervation. One week and 3-4 weeks following the sympathetic denervation, the animals were restudied following the above protocol. Ventilation was significantly lower following sympathetic denervation in normoxia and during the hypoxic exposure. However, the response to acute hypoxia and the time-course of ventilatory acclimatization to hypoxia was not altered by sympathetic denervation. All doses of norepinephrine and dopamine significantly inhibited VE in a dose-dependent manner. Sympathetic denervation did not significantly alter the response to the drug infusions. The sympathetic innervation to the CB does not appear to play a role in either the acute or prolonged ventilatory responses to hypoxia in the awake goat, but may affect overall ventilation.

Animals

The effect of dexamethasone on time averaged mean velocity in the middle cerebral artery in very low birth weight infants.

The effect of repeated doses of dexamethasone (0.25 mg/kg/dose every 12 h) on time averaged mean velocity in the middle cerebral artery was assessed in ten ventilated very low birth weight infants requiring treatment with dexamethasone for bronchopulmonary dysplasia or airway obstruction. The infants were studied by colour/duplex Doppler technique prior to the administration of the first and the third dose of dexamethasone, and 10, 30, and 120 min after these doses. Dexamethasone treatment was associated with an improvement in infant lung condition, an increase in mean arterial blood pressure and a decrease in heart rate. The time averaged mean velocity was statistically significantly reduced at 120 min after the first dose. This was not associated with a decrease in PCO2. The observed reduction of 18% from baseline in the time averaged mean velocity is unlikely to be of clinical importance.

Airway Obstruction

Modulation of respiratory rhythm by alpha 2-adrenoceptors in awake and anesthetized goats.

The purpose of this study was to examine the effects of alpha 2-adrenoceptor agonists in the control of breathing with goats that were either awake (n = 7) or anesthetized and artificially ventilated (n = 11). Awake goats infused intravenously with either of the alpha 2-agonists clonidine (1.0-6.0 micrograms/kg) or guanabenz (15.0-63.0 micrograms/kg) exhibited two distinct ventilatory patterns. One pattern was characterized by tachypnea in which respiratory frequency and minute ventilation increased to approximately 50% above control values. A second ventilatory pattern consisted of slow breathing with reductions of respiratory frequency and minute ventilation and highly variable expiratory duration intervals. These two patterns were unaffected by bilateral carotid body denervation. In anesthetized goats, alpha 2-agonists also caused an arrhythmia in phrenic nerve activity that was similar to the slow breathing pattern seen in awake goats. Respiratory disturbances were abolished by the selective alpha 2-receptor antagonist SKF-86466 (100-500 micrograms/kg), indicating that the effects are mediated by alpha 2-receptors. The results suggest that stimulation of alpha 2-adrenoceptors generally has an inhibitory effect on breathing in goats. The disruption of ventilation with clonidine or guanabenz suggests that alpha 2-adrenoceptors may play an important role in the control of central respiratory rhythm.

Adrenergic alpha-2 Receptor Agonists

Effect of indomethacin on cerebral blood flow velocities in very low birth weight neonates with a patent ductus arteriosus.

The effect of repeated doses of indomethacin on mean peak velocity (MPV) and time-averaged mean velocity in the middle cerebral artery was assessed in 10 ventilated neonates with a patent ductus arteriosus using colour/duplex Doppler technique prior to, and 10, 30, and 120 min after the first and the third dose. Velocities were significantly reduced up to 120 min after the first dose. The third dose resulted in a significant reduction in MPV at 10 and 30 min following treatment. This reduction was half of that observed after the first dose. Systemic blood pressure (BP) and heart rate did not change significantly after each separate dose. However, by the third dose, mean and diastolic BP were significantly increased from pretreatment levels. The attenuated response of cerebral blood flow (CBF) velocities to the third dose of indomethacin compared with the first dose is probably related to altered haemodynamics. Indomethacin should be used cautiously in infants with other conditions which are known to decrease CBF such as hypotension, hypocarbia and polycythaemia.

Blood Flow Velocity

Lung mechanics and oxygen consumption during spontaneous ventilation and severe heart failure.

The effects of acute heart failure on lung mechanics and oxygen consumption (VO2) during normocarbic spontaneous ventilation were studied in 21 anesthetized pigs. Heart failure severe enough to double oxygen extraction (O2ex) was induced with intravenous esmolol boluses and infusion. Compared to normal, the inspiratory elastic work of breathing (Wel) increased from 335 +/- 371 (mean +/- SD) to 559 +/- 48 mm Hg.ml (p less than 0.003) during heart failure, lung compliance (CL) fell from 121 +/- 144 to 22 +/- 15 ml/mm Hg (p less than 0.05), and respiratory power climbed from 140 +/- 200 to 245 +/- 214 mm Hg.ml.min-1 (p less than 0.002). These mechanical changes were accompanied by a decrease in both VO2 (221 +/- 61 to 191 +/- 50 mlO2/min, p less than 0.05) and oxygen delivery (DO2) (680 +/- 240 to 260 +/- 90 mlO2/min, p less than 0.004). The VO2/DO2 ratio doubled (p less than 0.0002), confirming increased O2ex. In conclusion, severe acute heart failure decreased CL, and increased Wel and respiratory power significantly. The depressed cardiac output limits both DO2, and to some extent, VO2. However, a greater proportion of the delivered O2 is consumed, supplying indirect evidence which suggests that the respiratory muscles' VO2 increases as a consequence of increased power expenditure.

Acute Disease

Cerebral-blood-flow-velocity measurements in neonates: technique and interobserver reliability.

The interobserver reliability for absolute cerebral-blood-flow-velocity measurements by colour and duplex Doppler sonography was tested in 32 neonates with a mean birth weight of 1489 (SD 644) g, and a gestational age of 29.9 (SD 3.5) weeks. Using standardized technique, two observers recorded on videotape, the Doppler spectrum of the anterior cerebral artery, the intracranial internal carotid artery and the middle cerebral artery. Peak systolic flow, end diastolic flow, mean flow velocity, resistive index and pulsatility index were computed from 3 consecutive waveforms by each observer. The estimates of interobserver reliability using the intraclass correlation coefficient of the examiners varied from 0.95 to 1.00. Therefore, cerebral blood flow velocity can be reliably measured in premature infants.

Blood Flow Velocity

Evaluation of direct pharmacist intervention on conversion from parenteral to oral histamine H2-receptor antagonist therapy.

A program in which pharmacists were authorized to change parenteral histamine H2-receptor antagonist (H2RA) therapy to the oral route without first contacting the prescriber was evaluated on cost and appropriateness of use of the parenteral route. Parenteral therapy was received by 264 and 244 patients in the study and comparison groups, respectively. Length of parenteral H2RA therapy was less in the study group (4.8 vs. 7.5 d) as was length of total (parenteral + oral) therapy (8.4 vs. 12.1 d). Parenteral H2RA drug acquisition savings were $6225 in the six-week study period or $53,950 when annualized. Decreased oral therapy contributed additional savings. There was a significant decrease in the number of inappropriate parenteral doses of ranitidine per patient, the drug used in more than 80 percent of the patients. In addition to the direct effect of pharmacists' interventions, there appeared to be an indirect effect of the program, as physicians initiated route of administration changes on their own.

Administration, Oral

Use of albumin in a university hospital: the value of targeted physician intervention.

Results of a preliminary study of albumin use at the University of Michigan Hospital were shared with one surgical service (thoracic surgery) that had a documented high rate of inappropriate use. To determine the effectiveness of this targeted educational intervention in reducing inappropriate use and associated drug costs, albumin prescribing for all adult inpatients at University Hospital over a 30-day period was assessed in a retrospective review. Eighty-six patients used a total of 843 units, a ten percent reduction in total albumin use. Albumin administration to thoracic surgery patients decreased by 38 percent. The 35 percent reduction in inappropriate albumin use by this service (Fisher's exact test, p less than 0.001) was associated with an estimated annual cost savings of +83,500. Inappropriate albumin use by other medical services generally increased over previously measured levels. This study demonstrated the effectiveness of targeted educational interventions in reducing inappropriate albumin use and thereby controlling rising healthcare costs.

Drug Utilization

Alternative work schedules for female pharmacists.

The impact of the increased proportion of women in pharmacy is discussed, and two leadership positions for which part-time work schedules were implemented are described. Issues associated with the increased representation of women include pharmacist shortages, loss of future leaders, decreased staff productivity related to inadequate day-care services, and a reduced earning potential of pharmacists. Many of these problems can be addressed by altering benefit packages and work schedules to enable employees to raise children while continuing to work. Specific strategies include legislation, day-care programs, flex time and flex scheduling, telecommuting, and the creation of alternative work schedules or permanent part-time positions. At the University of Michigan, a part-time position that combines faculty and clinical responsibilities has been in place since 1988. At The Washington Hospital Center, one of the three assistant director of pharmacy positions is part-time. The women in both positions have met or exceeded job performance requirements while raising a family. Issues raised by the increasing number of female pharmacists must be addressed by the profession. Part-time work schedules are one strategy for enabling female pharmacists to meet both their family and career responsibilities.

District of Columbia

Quality assurance program for a hospital investigational-drug service.

The development and implementation of a quality-assurance (QA) program for a pharmacy-based investigational-drug service are described. The objective of the QA program was to assess the quality of the activities in the areas of drug acquisition, inventory control, availability of drug data sheets and dispensing guidelines, provision of a quarterly drug accountability report, and documentation of drug dispensing to patients and decentralized pharmacy areas. The audit criteria were based on hospital policies and procedures and federal regulations for the handling of investigational drugs. Audits of four randomly selected protocols are conducted quarterly by a pharmacist who is not affiliated with the investigational drug service. The results of the first two audits have identified several areas for improvement, including the need for additional pharmacy staff education regarding study protocols, the importance of maintaining complete and accurate drug accountability records by decentralized pharmacists, and the need to provide a centralized source of study protocol information. The QA program has enabled the investigational-drug service to establish and enforce the policies and procedures for the appropriate handling of investigational drugs in this institution.

Drug Evaluation

Nurses' attitudes toward pharmaceutical services before and after decentralization.

Nurses' attitudes toward the quality of pharmaceutical services were assessed before and after the implementation of decentralized pharmaceutical services at a tertiary-care teaching hospital complex. The same multiple-choice questionnaire was distributed to nurses at the University of Michigan Hospitals 18 months before decentralized services were implemented (November 1982) and again after two satellite pharmacies had been established and a clinical pharmacist had begun providing first-dose dispensing services using a movable medication cart (March 1985). The questionnaire measured nurses' satisfaction with aspects of pharmaceutical services most likely to be affected by decentralization of services (e.g., number of missing medications, accessibility of pharmacists). Nurses' overall satisfaction with pharmaceutical services increased only slightly after services were decentralized. Significant positive changes in nurses' satisfaction occurred in areas served by the satellite pharmacies and the clinical pharmacist; no significant change s in satisfaction occurred in the other areas. Nurses' perceptions of increased helpfulness of pharmacy personnel were a better predictor of increased satisfaction than were changes in the number of missing medications, waiting time for medication delivery, or number of incorrectly dispensed medications. Respondents remained anonymous; therefore, changes in personnel, rather than changed opinions of nurses, may account for the differences in responses between 1982 and 1985. Nurses' attitudes toward pharmaceutical services improved in areas of the hospital served by satellite pharmacies or by a clinical pharmacist using a movable medication cart.(ABSTRACT TRUNCATED AT 250 WORDS)

Attitude of Health Personnel

Development and funding of a pharmacy-based investigational drug service.

The development, implementation, and operation of a pharmacy-based investigational drug service (IDS) at a university medical center are described. Before the IDS was established, pharmacy participation in investigational drug research was limited to the preparation of novel dosage forms. Medication errors, improper storage and labeling, and inadequate inventories of investigational drugs were common problems. Stepped-up enforcement by FDA and the National Cancer Institute (NCI) of guidelines for investigational drug control prompted the formation of a multidisciplinary task force, which recommended that the department of pharmaceutical services expand its support of investigational drug studies to include inventory control, record keeping, and clinical services. The IDS is supported by both the hospital and the school of medicine and currently receives 36% of its funding from principal investigator grants and contracts. The IDS coordinates more than 100 study protocols and dispenses more than 4000 doses of investigational drugs annually. The IDS is staffed by 1.0 full-time equivalent (FTE) clinical pharmacist and 0.5 FTE technician. Inventory control and billing functions are performed by a departmental microcomputer system. The IDS has demonstrated a positive gross margin for each of its first two years of operation. Problems associated with the control and use of investigational drugs at this institution have been successfully corrected by the implementation of a pharmacy-based IDS.

Drug Evaluation

Mitochondrial genetics of mammalian cells: a mouse antimycin-resistant mutant with a probable alteration of cytochrome b.

Mouse LA9 antimycin-resistant mutants (ANT-R) were isolated and characterized. Genetic analyses established that this phenotype is encoded within the mtDNA: (1) the ANT-R phenotype showed frequent mitotic segregation and reassortment in hybrid clonal lines; (2) it was transmitted directly in cybrid crosses; and (3) it was cotransmitted in cybrid crosses with the mitochondrial CAP-R marker. Furthermore, the genetic studies suggested that the LA9 CAP-R ANT-R cells were heteroplasmic and contained at least two mtDNA genotypes, cap-r ant-s and cap-s ant-r. Cellular respiration of the ANT-R mutant was markedly more resistant to inhibition by antimycin than that of the parental ANT-S cells. The increased resistance of cellular respiration was entirely accounted for by an increase in the resistance of mitochondrial succinate-cytochrome c oxidoreductase to antimycin inhibition. There was no detectable change in the specific activity of the oxidoreductase in mitochondria of resistant ANT-R cells nor in the sensitivity of the complex to three other specific inhibitors of the complex: TTFA, myxothiazol, and HQNO. Taken together, these studies indicate that the ANT-R phenotype is most likely encoded within the mitochondrial cytochrome b gene and, more specifically, within an antimycin binding domain.

Animals