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Biomedical subjects

M J Ryan

Publications and source records attributed to M J Ryan.

At least 73 records · Page 4Linked to original sources

Outbreaks of salmonellosis in hospitals in England and Wales: 1992-1994.

Data from the surveillance scheme of general outbreaks of infectious intestinal disease in England and Wales were used to describe the epidemiology of outbreaks of salmonellosis in hospitals from 1992-1994. Outbreaks of infectious intestinal disease in hospitals accounted for 15% (189/1275) of all outbreaks. A salmonella was the implicated pathogen in 12% (22/189). The mode of transmission was described as mainly person to person in 12 outbreaks, mainly foodborne in eight and equal or unknown proportions of foodborne and person to person in two. The most common strain involved was Salmonella enteritidis PT4 (11 outbreaks). The mean duration of outbreaks was 16 days. The mean attack rate in patients was 25% but varied from 2-67%. Illness was reported in 260 patients, of whom 130 had a laboratory confirmed infection. Eight hundred and twenty-six asymptomatic patients were tested, 31 of whom were positive. The salmonella infection was believed to have contributed to the deaths of five patients. Ill staff (115) were tested and 68 were positive; 1508 well staff were tested and 33 were positive. Outbreaks of salmonellosis in hospitals are preventable. Attack rates can be high and outbreaks are often prolonged, with high morbidity and associated disruption of hospital services. There is need for effective infection control policies, appropriate training of staff, simple surveillance systems and readily available expert advice to ensure outbreaks are rapidly controlled.

Cross Infection↗

Hospital admissions attributable to rotavirus infection in England and Wales.

Laboratory reports and data on hospital admissions were used to estimate the number of hospitalizations due to group A rotavirus infection in England and Wales. Between January 1990 and December 1994, there were 75,059 laboratory reports of rotavirus infection, and 66,062 of these were in children <5 years old; rotavirus represented 39% of all pathogens identified in fecal specimens from this age group. Between April 1993 and March 1994, 1904 hospital admissions coded as "infectious intestinal disease" and 2354 coded as "noninfective gastroenteritis" occurred in children <5 in the North Thames region (a health authority representing 13% of the population in England and Wales). By modeling admission and laboratory reporting data, it was estimated that 54% of hospitalizations for intestinal infectious disease and 34% for noninfective gastroenteritis were attributable to rotavirus. By extrapolation of the North Thames data, it was estimated that 17,810 rotavirus-related hospitalizations (5/1000 children <5 years old) occurred in England and Wales during the same period. Effective vaccines have the potential to substantially reduce the number of hospital admissions due to group A rotavirus infection.

Adolescent↗

Correlations between call characteristics and morphology in male cricket frogs (Acris crepitans).

We investigated the relationships among spectral and temporal advertisement-call characteristics and the sizes of the laryngeal and ear components thought to underlie the generation and reception of species-specific vocalizations in male cricket frogs (Acris crepitans). We tested the predictions that the volumes of the structural elements necessary for acoustic communication would be correlated with various parameters of the vocalizations. The anatomy of laryngeal and ear structures was reconstructed from serial sections of the heads of male cricket frogs of two subspecies collected from several sites across the range of this species in Texas, USA. The relationships among the anatomy and call parameters were assessed using several univariate and multivariate analyses. Highly significant univariate correlations among the laryngeal components suggest that the temporal and spectral characteristics of the calls are not independently produced. Dominant frequency correlates strongly with most of the other call and morphological characteristics. Removing body size effects, however, removes the relationship between dominant frequency and the volume of the whole larynx and ear. This is also the case for call pulse rate, indicating that for this species both spectral and temporal call parameters are biomechanically related to laryngeal size which is, in turn, largely mediated by body size. General body size effects might also explain the existence of significant relationships between ear size and temporal characteristics of the call that probably do not have a functional basis.

Analysis of Variance↗

Frameless stereotaxy with real-time tracking of patient head movement and retrospective patient-image registration.

The accuracy of a novel frameless stereotactic system was determined during 10 surgeries performed to resect brain tumors. An array of three charge-coupled device cameras tracked the locations of infrared light-emitting diodes on a hand-held stylus and on a reference frame attached to the patient's skull with a single bone screw. Patient-image registration was achieved retrospectively by digitizing randomly chosen scalp points with the system and fitting them to a scalp surface model derived from magnetic resonance (MR) images. The reference frame enabled continual correction for patient head movements so that registration was maintained even when the patient's head was not immobilized in a surgical clamp. The location of the stylus was displayed in real-time on cross-sectional and three-dimensional MR images of the head; this information was used to predict the locations of small intracranial lesions. The average distance (and standard deviation) between the actual position of the mass and its stereotactically predicted location was 4.8 +/- 3.5 mm. The authors conclude that frameless stereotaxy can be used for accurate localization of intracranial masses without resorting to using fiducial markers during presurgical imaging and without immobilizing the patient's head during surgery.

Adult↗

Evaluation of physicochemical parameters important to the oral bioavailability of peptide-like compounds: implications for the synthesis of renin inhibitors.

A series of radiolabeled compounds related to renin inhibitor structures was synthesized to represent a range of physicochemical properties. These compounds were tested in assays for intestinal absorption and hepatic clearance in order to define parameters conducive to optimizing bioavailability. In general, compounds with higher lipophilicity were better absorbed from the intestine. Absorption may also be dependent on molecular charge, as compounds with ionizable functionality were less well-absorbed than neutral compounds. Neutral compounds showed some dependency on molecular weight, with smaller compounds exhibiting better absorption. While uptake into hepatic cells was rapid regardless of partition coefficient or molecular weight, rate of appearance in bile was dependent on the molecular weight of the compounds.

Administration, Oral↗

Pharmacologic characterization of CI-996, a new angiotensin receptor antagonist.

CI-996, a novel potent angiotensin II (Ang II) type 1 (AT1) receptor antagonist was characterized in a number of in vitro and in vivo assays. In addition, CI-996 was compared with several reported AT1 receptor antagonists including losartan, SK&F 108566 and L-158,809. In rat liver membranes CI-996 displaced specifically bound [125I]Ang II with an IC50 of 0.8 +/- 0.1 nM. In isolated rabbit aorta CI-996 produced a concentration-dependent inhibition of Ang II-induced contraction and decreased the maximal contractile response to Ang II. CI-996 had no effect on the contractile responses to KCl, norepinephrine or endothelin. In anesthetized, ganglionic-blocked rats CI-996 produced dose-dependent inhibition of the Ang II pressor dose-response curve with an IC50 of 6.2 micrograms/kg/min i.v. Orally administered CI-996 dose dependently lowered mean arterial blood pressure in conscious renal hypertensive rats, conscious sodium-depleted dogs, conscious sodium-depleted monkeys and conscious renal hypertensive monkeys. The duration of antihypertensive activity of CI-996 in rats was > 24 hr after a single oral dose. The blood pressure lowering potency of CI-996 in dogs was less than that observed in either rats or monkeys. There was no tachyphylaxis to the antihypertensive effects of CI-996 after repeated administration in renal hypertensive monkeys. These data demonstrate that CI-996 is a potent, selective Ang II antagonist. Furthermore, CI-996 has demonstrated blood pressure-lowering activity after oral administration in rats, dogs and monkeys.

Angiotensin II↗

Benefit to male sailfin mollies of mating with heterospecific females.

Female gynogens reproduce clonally but rely on sperm from heterospecific males to initiate embryogenesis. It has been assumed that males gain no benefit from such matings; thus, selection should favor males that avoid them. Here it is shown that males gain a benefit by mating with female gynogens in an asexual-sexual complex of fish. The sexual females increase their preference for males whom they observe consorting with female gynogens. Thus, gynogenetic species might persist because selection favors males to be sexually parasitized.

Animals↗

HK-2: an immortalized proximal tubule epithelial cell line from normal adult human kidney.

Studies assessing mechanisms of proximal tubular cell (PTC) physiology and pathophysiology increasingly utilize cell culture systems to avoid the complexity of whole organ/whole animal experiments. However, no well-differentiated PTC line derived from adult human kidney currently exists. Therefore, the goal of this research was to establish such a line by transduction with human papilloma virus (HPV 16) E6/E7 genes. A primary PTC culture from normal adult human renal cortex was exposed to a recombinant retrovirus containing the HPV 16 E6/E7 genes, resulting in a cell line designated HK-2 (human kidney-2) which has grown continuously in serum free media for more than one year. HK-2 cell growth is epidermal growth factor dependent and the cells retain a phenotype indicative of well-differentiated PTCs (positive for alkaline phosphatase, gamma glutamyltranspeptidase, leucine aminopeptidase, acid phosphatase, cytokeratin, alpha 3 beta 1 integrin, fibronectin; negative for factor VIII-related antigen, 6.19 antigen and CALLA endopeptidase). Furthermore, HK-2 cells retain functional characteristics of proximal tubular epithelium (Na+ dependent/phlorizin sensitive sugar transport; adenylate cyclase responsiveness to parathyroid, but not to antidiuretic, hormone). The E6/E7 genes are present in the HK-2 genome, as determined by PCR. To assess its potential usefulness as a tool for studying injury and repair, HK-2 cells were exposed to a toxic concentration of H2O2 +/- iron chelation (deferoxamine) or hydroxyl radical scavenger (Na benzoate) therapy. Only the former blocked H2O2 cytotoxicity, reproducing results previously obtained with freshly isolated rat proximal tubular segments. In conclusion, an immortalized adult human PTC line has been established by transduction with HPV 16 E6/E7 genes. It appears to be well-differentiated on the basis of its histochemical, immune cytochemical, and functional characteristics, and it can reproduce experimental results obtained with freshly isolated PTCs. Thus, this new PTC line could have substantial research application.

Adult↗

A key informant "tree" as a tool for community oriented primary care. The Cleveland COPC Group.

OBJECTIVE: Although community oriented primary care (COPC) is conceptually appealing, lack of practical methodology has limited its application. To implement the initial portions of COPC, most practitioners need to have available inexpensive, quick methods of doing community assessment. Use of community members identified as key informants is one method for conducting the qualitative portion of a community assessment. A key informant "tree" was developed at an inner city health center to analyze its costs, benefits, and limitations as a tool for COPC. METHODS: Using a semi-structured format, 14 of 24 key informants were interviewed using open-ended, closed-ended, and rating questions. An analysis was conducted of the costs of this approach and of the responses received. RESULTS: Planning and implementation of the tree took 6 hours of physician time and 8 hours of nonphysician time. Useful data was obtained from each of the different types of questions, although it appeared best suited to open-ended questions. Response bias was an important problem. The key informant approach appeared most useful with informal community leaders. CONCLUSIONS: With appropriate recognition of the potential biases, key informant trees appear to be a practical and clinically useful tool for the subjective portion of the community assessment component of COPC.

Community Health Services↗

Effect of an orally active renin inhibitor Cl-992 on blood pressure in normotensive and hypertensive monkeys.

Cl-992, a novel potent inhibitor of primate renin, was tested for blood pressure-lowering efficacy in sodium-restricted, furosemide-treated conscious normotensive cynomolgus monkeys and conscious renal hypertensive monkeys. The hypertensive monkey model provided an opportunity to determine the response to a renin inhibitor in a pathological nonhuman primate model of hypertension without concurrent diuretic treatment or dietary sodium restriction and on repeated oral administration. Cl-992 has IC50 values of 0.58 +/- 0.06 (n = 4) and 0.36 +/- 0.03 nM (n = 8) against human and monkey renin, respectively. In normotensive monkeys, oral Cl-992 at doses of 3, 10 and 30 mg/kg reduced mean arterial blood pressure (MABP) by 8 +/- 2, 15 +/- 7 and 29 +/- 7 mm Hg (n = 5 animals per dose level, P < .05), respectively (base line, 103 +/- 3 mm Hg). Intravenous Cl-992 (0.0001 to 0.1 mg/kg) also caused dose-dependent decreases in MABP and a maximum reduction of 23 +/- 4 mm Hg. The decrease in MABP after Cl-992 was paralleled by an inhibition of plasma renin activity (PRA) and a reduction in immunoreactive angiotensin II. In renal hypertensive monkeys, oral Cl-992 at doses of 3, 10 and 30 mg/kg reduced MABP by 6 +/- 2, 18 +/- 6 and 37 +/- 8 mm Hg (n = 3 or 4, P < .05), respectively (base line, 134 +/- 4 mm Hg).(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral↗

Disparity between blood pressure and PRA inhibition after administration of a renin inhibitor to anesthetized dogs: methodological considerations.

A dissociation between changes in blood pressure (BP) and plasma renin activity (PRA) has been noted after administration of renin inhibitors. In the present study, the renin inhibitor PD 132002 was given to salt-deplete, anesthetized dogs. PRA was measured at pH 6.0 by a conventional angiotensin I (ANG I) RIA method (PRA-C) and by an ANG I antibody-trapping RIA method (PRA-AT) performed at pH 7.4. PD 132002 at 0.01, 0.1, 1, and 10 mg/kg IV, reduced BP by 3 +/- 2, 9 +/- 2, 24 +/- 4, and 39 +/- 4 mm Hg, respectively, (baseline of 136 +/- 8 mm Hg, N = 5), when infused IV over 30 minutes with a 30 minute recovery between doses. The BP response at 10 mg/kg equaled that of saralasin (20 micrograms/kg/min IV). PRA-AT (baseline of 20 +/- 6 ng ANG l/ml/hr, N = 4) was inhibited by 0%, 28% +/- 12%, 75% +/- 10%, and 97% +/- 1% at 0.01, 0.1, 1, and 10 mg/kg, respectively. Plasma concentrations of immunoreactive ANG II were also reduced dose-dependently and paralleled changes in BP. In contrast, PRA-C (baseline of 13 +/- 4 ng ANG l/ml/hr, N = 4) was inhibited by 82% +/- 8% at 0.01 mg/kg and by > 98% at higher doses. After a single dose of PD 132002 at 10 mg/kg infused over 30 minutes, BP recovery paralleled changes in immunoreactive ANG II and PRA-AT, yet PRA-C inhibition showed no recovery over the same time course. Our data support the conclusion that BP relates better to PRA-AT than PRA-C. Thus the dissociation sometimes observed in studies with renin inhibitors between changes in BP and PRA may be attributed to the assay used to determine PRA.

Animals↗

An investment in leadership. A system's three-year trainee program gives young executives a career head start.

The SSM Health Care System (SSMHCS), St. Louis, recently instituted a three-year leadership training program for new graduates in health administration. Participants spend one year in a rural facility, where they perform line and staff functions. They spend another year in a corporate staff role, gaining experience in areas such as finance, planning, marketing, human resources, mission and values, and regional operations. In the third year, participants concentrate on an area of their choice and begin to search for a permanent job within the system. SSMHCS sought candidates who: Were open to working in both urban and rural settings and were willing to relocate when necessary. Had the potential to move into a permanent managerial position within three years. Were willing to consider line and staff roles. Showed an interest and ability to work in the Catholic healthcare ministry. The advantage of the trainee program over traditional fellowships is that it gives the program participant a genuine start on a career rather than a mere extension of his or her education. For SSMHCS the opportunity to train young managers and administrators is an investment in the future.

Career Mobility↗

The future is continuous quality improvement.

The SSM Health Care System is a Catholic, not-for-profit, multihospital health care system with headquarters in St. Louis, Missouri. Sister Mary Jean Ryan, FSM, the President and Chief Executive Officer, has led the implementation of continuous quality improvement (CQI) throughout the system since 1990. This article presents excerpts from a speech Sister Ryan delivered at the system's annual leadership conference in 1990. Sister Ryan delivered this speech at the conclusion of a retreat where the principles of CQI were introduced to the SSM Health Care System leadership. The editors believe this inspiring speech provides insight into the kind of leadership needed to successfully implement quality management.

Catholicism↗

Structure-activity relationships of a series of 2-amino-4-thiazole-containing renin inhibitors.

A series of renin inhibitors was synthesized that contained a 2-amino-4-thiazolyl moiety at the P2 position. These derivatives are potent inhibitors of monkey renin in vitro and are selective in that they only weakly inhibit the closely related aspartic proteinase, bovine cathepsin D. Four compounds exhibited oral blood pressure lowering activity in high-renin normotensive monkeys. One of these compounds, 22 (PD 134672), was selected for further evaluation in renal hypertensive monkeys, on the basis of its superior efficacy and duration of action in the in vitro assays and the normotensive primate model.

Animals↗