The renin-angiotensin-aldosterone system in experimental mineralocorticoid-salt-induced cardiac fibrosis.
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Aldosterone↗
Biomedical subjects
M J Young
Publications and source records attributed to M J Young.
Role of telemetry monitoring in the non-intensive care unit.
To determine the outcomes of patients admitted to a non-intensive care telemetry unit and to assess the role of telemetry for guiding patient management decisions, data from 2,240 patients admitted to a telemetry unit were collected prospectively during 7 months. Physicians recorded the outcomes (intensive care unit transfer and mortality) and assessed whether telemetry assisted in guiding patient management. Indications for admission to the telemetry unit included chest pain syndromes (55%), arrhythmias (14%), heart failure (12%), and syncope (10%). Telemetry led to direct modifications in management in 156 patients (7%; 95% confidence interval [CI] 5.9% to 8%). Telemetry was perceived as useful but did not alter management for 127 patients (5.7%; 95% CI 4.7% to 6.6%). Two hundred forty-one patients were transferred to an intensive care unit from the telemetry unit (10.8%; 95% CI 9.5% to 12%). Nineteen patients (0.8% of all admissions; 95% CI 0.5% to 1.2%) were transferred because of an arrhythmia identified by telemetry. Routine transfer after cardiac revascularization or surgery accounted for 134 transfers; clinical deterioration accounted for 88 transfers. There were 20 deaths in the unit (0.9%; 95% CI 0.5% to 1.3%): 4 of the 20 deaths occurred while patients were being monitored. The role of telemetry in guiding patient management may be overestimated by physicians, since it detected significant arrhythmias that led to change in medications or urgent interventions in a small fraction of patients.
Aged↗
Interactive events subserving the pupillary light reflex in pigmented and albino rats.
The consensual pupilloconstrictor response requires the intensity information that is delivered to each eye to be integrated to produce an averaged response such that the pupillary diameter in each eye is equal. Here we have examined how luminance information from each eye is integrated in the rat and where the integration occurs, using a pupillometry system to record pupillary diameter after illumination of one or both eyes. In albino rats the size of the uncrossed optic pathway to the pupilloconstrictor centre, the olivary pretectal nucleus, is reduced three-fold and there is a concomitant but less dramatic reduction in the size of the consensual response. Unilateral lesions of the olivary pretectal nucleus in pigmented rats restrict all optic input to the opposite pretectum. Stimulation of one or both eyes in these animals suggests that integration occurs not only at the level of the olivary pretectal nucleus, but also downstream in the Edinger-Westphal nucleus. Parallels with human studies and the opportunity to perform secondary lesions suggests the rat may provide a good model in which to study the substrates of the pupilloconstrictor response and mechanisms of integration of convergent parallel inputs in general.
Animals↗
In vitro assembly of cowpea chlorotic mottle virus from coat protein expressed in Escherichia coli and in vitro-transcribed viral cDNA.
The small spherical plant virus, cowpea chlorotic mottle virus (CCMV), provides an ideal system to examine spherical virus assembly. We have modified the CCMV in vitro assembly system to produce virions from coat protein expressed in Escherichia coli and viral RNA transcribed in vitro from full-length cDNAs. Examination of the in vitro-assembled particles with cryoelectron microscopy and image reconstruction techniques demonstrates that the particles are indistinguishable from plant purified particles at 2.5 nm resolution. Mutational analysis of the coat protein N- and C-terminal extensions demonstrate their respective roles in virus assembly. The N-terminus is required for assembly of RNA containing particles but not for the assembly of empty virions. The C-terminus is essential for coat protein dimer formation and particle assembly.
Base Sequence↗
Restoring lower limb blood flow improves conduction velocity in diabetic patients.
Human diabetic peripheral neuropathy is believed to have, at least in part, a microvascular basis. This study was designed to examine the effects of restoration of arterial blood supply on peripheral nerve function in six non-insulin-dependent diabetic patients with peripheral occlusive vascular disease. In the revascularised legs, transcutaneous oxygen increased from a median 37.5 (28.5-45.7 interquartile range) mmHg to 55.5 (53.5-62.5) mmHg, p = 0.036, mean increase 20.2 (14.8-25.6, 95% confidence intervals(CI) mmHg. This was accompanied by a significant improvement in peroneal motor nerve conduction velocity from 31.7 (26.5-36.3) m/s to 33.5 (32.9-39.4) m/s, p = 0.04, mean increase 4.7 (1.7-7.7, 95% CI) m/s. There was no significant change in transcutaneous oxygen or peroneal nerve motor conduction velocity in the contralateral control limbs. This improvement in conduction velocity with improved tissue oxygenation suggests that studies of agents which might indirectly bring about improvements in microvascular blood flow should be urgently considered.
Aged↗
Excess maternal history of diabetes in Caucasian and Afro-origin non-insulin-dependent diabetic patients suggests dominant maternal factors in disease transmission.
We examined the records of 2576 patients with non-insulin-dependent diabetes mellitus (NIDDM) and categorised them according to race and family history of diabetes. Family history of diabetes is known to play an important role in the development of NIDDM, and a maternal history is thought to be most influential. We found that a maternal history of diabetes was present in 60% of Caucasian and West Indian patients with a parental history of diabetes, whereas in Asian patients the figure was only 34%. Asian men were also more likely to have a father with diabetes. This anomaly may be due to cultural differences in the reporting of the disease. Our data support the dominant maternal role in the development of NIDDM in their offspring and suggest an under-reporting of NIDDM in Asian females.
Africa↗
Reliability of the clinical assessment in predicting the cause of internal derangements of the knee.
The reliability of the clinical assessment, which comprised history, physical examination, and plain radiographs, was determined by comparing the initial preoperative diagnosis with the postoperative diagnosis as determined arthroscopically, and by comparing the results of the clinical evaluation with published reports of arthrography, computed tomography (CT), and magnetic resonance imaging (MRI). The study group included 206 patients (216 knees) scheduled for arthroscopic surgery for suspected internal derangements. The primary preoperative clinical diagnosis was correct in 175 knees (81%), with an overall accuracy of 93%, sensitivity of 89%, and specificity of 94%. The most common preoperative diagnoses were medial and lateral meniscal tears. Results of the clinical assessment were comparable or superior to published reports of arthrography, CT, and MRI. Thus, it may be unnecessary to routinely use these costly special studies to determine the need for arthroscopic surgery. We conclude that a thorough clinical assessment can provide sufficient information for the surgeon to make a definitive primary preoperative diagnosis, and that arthroscopy should not be performed without first completing a complete preoperative examination.
Adolescent↗
A code of practice on dealing with infectious diseases on aircraft.
Increasing numbers of people are travelling to and from more distant destinations with the possibility of exposure to common as well as exotic disease. At the present time there are no readily accessible rules or guidance for dealing with possible cases of infectious disease occurring during international flights. A 'Code of Practice on dealing with infectious disease on aircraft' is proposed as a ready means of dealing with the problem without excessive action or expense.
Aircraft↗
Osteopenia, neurological dysfunction, and the development of Charcot neuroarthropathy.
OBJECTIVE: To determine factors that might be associated with the development of Charcot neuroarthropathy. RESEARCH DESIGN AND METHODS: This cross-sectional prevalence study examined neurological function and bone density in matched groups of neuropathic diabetic patients with and without radiological evidence of Charcot neuroarthropathy. RESULTS: Patients with Charcot neuroarthropathy had a global impairment of neurological function that was significantly greater than that of otherwise matched non-Charcot neuropathic patients. All 17 Charcot patients had evidence of autonomic neuropathy compared with 10 of the control subjects (P = 0.03). The Charcot patients had evidence of reduced bone density in the lower limbs compared with the neuropathic control subjects (P = 0.009), but relatively preserved bone density in the spine (P = 0.4 vs. control subjects). CONCLUSIONS: We conclude that minor trauma in diabetic patients with peripheral neuropathy might result in a fracture in those with a reduced bone density and thus trigger the development of Charcot neuroarthropathy.
Bone Density↗
Patients, physicians, and professional knowledge: implications for CQI.
As we consider how to improve health care, we must understand the transformation that focuses on the physician's role in health care. A multidisciplinary team is critical for improvement activities-hospital administrators, nurses, and other colleagues. All need to learn new knowledge and leadership skills, but there is a special need to understand underlying issues that will require a transformation in many physicians. This will not be easy--nor should it be. Physicians must continue to achieve the benefits for patients that come from traditional professional knowledge. However, there is an even greater need to understand how physicians can move from the dominance approach of the medical model to a partnership approach inherent in CQI. This article describes lessons learned from our CQI work with physician colleagues over the last several years. First the relationship of professional knowledge to knowledge for improvement is described, and then the individual patient-doctor relationship is reexamined. Next, the implications of knowledge for improvement for the roles of physicians in organized health care systems are considered.
Clinical Competence↗
In vivo expression and mutational analysis of the barley yellow dwarf virus readthrough gene.
The barley yellow dwarf virus (BYDV) coat protein gene is separated from an adjacent downstream open reading frame (ORF) by a single termination codon. Immunological analysis of this downstream "readthrough" region reveals multiple coat protein-readthrough products. A full-length 72-kDa (P72) coat protein-readthrough fusion product is detected in total lysates from infected cells. However, purified aphid transmissible virions contain only a 50-kDa (P50) coat protein-readthrough product. Virion-associated P50 lacks the C-terminal domain predicted by its ORF sequence. A separate 33-kDa polypeptide (P33) corresponding to the readthrough C-terminus domain is detected in the crude cellular membrane fraction. Site-directed and deletion mutational analysis demonstrate that the readthrough ORF is dispensable for BYDV replication and virion accumulation in protoplasts. In contrast, a mutant which results in a continuous fusion product of coat and readthrough sequences is not viable. Point mutations were used to map regions required for P50 and P72 synthesis. A model explaining the relationships between the three forms of the readthrough polypeptides is proposed.
Base Sequence↗
The vaccination status of aboriginal children in the North Coast Health Region of New South Wales.
OBJECTIVE: To determine the vaccination status of Aboriginal children resident in the North Coast Health Region of NSW. DESIGN: Cross-sectional descriptive study. SETTING AND PARTICIPANTS: The vaccination status of Aboriginal children aged 4 months to 11 years and resident in selected villages/isolated communities, small and large towns in the North Coast Health Region of NSW was determined by review of vaccination records. Data were obtained from general practitioners, the Aboriginal Health Service, Community Health Centres and Local Government Councils. MAIN OUTCOME MEASURES: Vaccination status according to the childhood immunisation schedule recommended by the National Health and Medical Research Council, defined as fully or partially documented, with a generous lag time. RESULTS: The study population comprised 1179 children--55% of the estimated Aboriginal population under 12 years of age in the North Coast Health Region. Data collection on Sabin vaccine was incomplete and was not included in the analysis. Of 1094 children whose records were analysed, 9% had fully documented and 27% fully or partially documented evidence of up-to-date vaccinations. For measles vaccination, 28% of children aged 18 months or more had fully documented and 35% fully or partially documented evidence of vaccination. There was no fully documented evidence of any vaccinations for 52% of children. CONCLUSION: The vaccination status of Aboriginal children in the North Coast Health Region is poor. The 1989-1990 National Health Survey showed overall vaccination rates for NSW and Australia to be more than twice those found for this population.
Child↗
Outcomes of patients hospitalized to a telemetry unit.
To describe the clinical course of patients admitted to a nonintensive care telemetry unit and to determine whether telemetry identifies patients at risk for transfer to the intensive care unit (ICU), 467 patients hospitalized for cardiac monitoring in a nonintensive care telemetry unit were followed until death or discharge. The American College of Cardiology guidelines for telemetry use were applied: 65% of patients were class I (monitoring definitely indicated); 33% class II (probably indicated); and 2% class III (not indicated). In 5 patients (1%), telemetry contributed to the decision for a transfer to the ICU. In 462 patients, telemetry added no significant information. Thirty-eight patients (8.1%) were transferred to an ICU: 22 because of cardiac deterioration and 16 because of noncardiac clinical deterioration. Eighteen percent of patients in class I (95% confidence interval [CI], 14.1 to 22.8), 12% in class II (95% CI, 6.7 to 17), and none in class III (95% CI, 0 to 26) were transferred to the ICU (p = 0.03). Nine patients died (1.9%), 4 with terminal illness. Three patients died while on telemetry: 1 had metastatic lung cancer and 2 died suddenly of cardiac causes during initial evaluation on the ward. Telemetry identified the terminal rhythm in the 3 patients. Patients admitted to a non-ICU monitored ward with ischemic syndromes, heart failure, and arrhythmia rarely deteriorated. Patients who did deteriorate were recognized clinically without appreciable contribution from the monitoring process. It remains unproven that heart rhythm monitoring in general practice units improves patient care.
Arrhythmias, Cardiac↗
In vivo evaluation of anterior cervical fusions with hydroxylapatite graft material.
STUDY DESIGN: The efficacy of solid hydroxylapatite (HA) blocks for obtaining cervical interbody fusion was studied in a canine model. Each of 21 adult colony-reared hounds received a hydroxylapatite implant and an autogenous bone graft in the C3-C4 and C5-C6 disc interspaces. Seven dogs each were killed at 6, 12, and 26 weeks postoperation. OBJECTIVE: This study determined the rate, mechanical strength, and histologic characteristics of cervical interbody fusions achieved using a hydroxylapatite (HA) block and compared the results to those obtained with autogenous iliac crest bone graft. SUMMARY OF BACKGROUND DATA: The use of corticocancellous autograft has been successful in a high percentage of anterior cervical interbody fusions. Calcium phosphate ceramics may provide an alternative to autogenous and allogenous tissue. These materials are biocompatible and capable of direct intimate bonding with bone because of their chemical similarity to bone mineral. METHODS: Radiographic evaluation including plain radiographs, computed tomography (CT), and magnetic resonance imaging (MRI) studies were used to determine fusion quality. Specimens were also subjected to mechanical testing to determine bending and torsional stiffness as well as ultimate load to failure. Histologic evaluation included integrity and incorporation of the graft materials and interface characterization. RESULTS: The CT images were well correlated with plain radiographs and demonstrated progressive incorporation of the graft materials with time. Magnetic resonance images were of little value in evaluating quality of fusion; the autograft sites demonstrated progressive disc height loss with time. Minimal disc height loss was observed with HA blocks. There was no statistical difference in torsional stiffness for the HA blocks and autogenous bone grafts at any time period. In bending, the HA block sites were significantly stiffer at 6 weeks (P < 0.005). There was no statistical difference in the ultimate failure load for the HA and autogenous bone grafts. Histologically, the HA blocks demonstrated areas of direct bone apposition with increased bone appositions and implant incorporation with time. At 6 and 12 weeks postoperation, the autograft sites demonstrated areas of graft resorption and some new bone formations. By 26 weeks, new bone was continuous with the vertebral endplates. CONCLUSIONS: The results indicate that HA blocks may provide an alternative to autogenous graft materials for anterior cervical interbody fusion. Block slippage and/or fracture may occur in a small number of patients but is primarily related to insertion technique and does not appear to significantly alter the final result.
Animals↗
Dr Deming and primary care internal medicine.
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Clinical Competence↗
Validation of a clinical prediction rule for the differential diagnosis of acute meningitis.
OBJECTIVE: To attempt to validate a previously reported clinical prediction rule derived to assist in distinguishing between acute bacterial meningitis and acute viral meningitis. DESIGN: Retrospective chart review of patients treated at five hospitals between 1981 and 1990. The criterion standard for bacterial meningitis was a positive cerebrospinal fluid (CSF) or blood culture or a positive test for bacterial antigen in the CSF. For viral meningitis, the criterion standard was a positive viral culture from CSF, stool, or blood or a discharge diagnosis of viral meningitis with no other etiology evident. SETTING: Two Department of Veterans Affairs (VA) hospitals, two county hospitals, and one private hospital, each affiliated with one of two medical schools. PATIENTS: All persons aged more than 17 years who were hospitalized over a ten-year period at one of five academically affiliated hospitals for the management of acute meningitis. MEASUREMENTS AND MAIN RESULTS: Sixty-two cases of bacterial meningitis and 98 cases of viral meningitis were confirmed. With all patients included, the discriminatory power of the model as measured by the area under the receiver operating characteristic curve (AUC) was 0.977 (95% CI, 0.957-0.997), compared with the AUC of 0.97 in the derivation set of the original publication. The AUCs (95% CIs) for data subsets were: Dallas cases 0.994 (0.986-1.0). Milwaukee cases 0.912 (0.834-0.990); ages 18-39 years 0.952 (0.892-1.0), ages 40-59 years 0.99 (0.951-1.0), and age > or = 60 years 0.955 (0.898-1.0). CONCLUSIONS: The authors conclude that the clinical prediction rule proved robust when applied to a geographically distinct population comprised exclusively of adults. There was sustained performance of the model when applied to cases from each city and from three age strata. Prospective validation of this prediction rule will be necessary to confirm its utility in clinical practice.
Acute Disease↗
The anatomical substrates subserving the pupillary light reflex in rats: origin of the consensual pupillary response.
While the olivary pretectal nucleus has been shown to be central to the pupillary constriction response in rats, it is not at all clear at which level the consensual response is generated. To examine this we have investigated the efferent projections of this nucleus, as well as the effect of unilateral lesions of the olivary pretectal nucleus, on the direct and consensual pupillary light reflexes. The results demonstrate that the olivary pretectal nucleus projects bilaterally to the Edinger-Westphal nucleus, as well as to the nucleus of the posterior commissure, which itself projects bilaterally to the Edinger-Westphal nucleus. The olivary pretectal nucleus also projects to the ipsilateral ventral lateral geniculate nucleus. Unilateral lesions of the olivary pretectal nucleus decrease, but do not abolish, the direct and consensual pupillary light reflexes by as much as 66%. Since some degree of consensual response remains, this is likely to be due to the bilateral projection from the olivary pretectal nucleus, either directly or indirectly through the nucleus of the posterior commissure, to the Edinger-Westphal nucleus. These results show that while the bilateral projection from the olivary pretectal nucleus to the Edinger-Westphal nucleus contributes to the consensual pupillary light reflex, the bilateral retinal projection to the olivary pretectal nucleus is the more determinant component of the pathway. In addition to providing insights into the anatomical substrates of the pupillary response, this work also provides a background to ongoing studies of the retinal graft-mediated pupillary light reflex, as well as serving as a model of a relatively simple reflex system.
Animals↗
Continuously improving primary care.
BACKGROUND: This article describes efforts to understand and improve the daily work processes of primary care within the Henry Ford Health System, where continuous quality improvement (CQI) has been a key business strategy since 1988. We began a pilot project in 1990 that attempted to accelerate the implementation of continuous improvement in primary care. The clinical site was the general internal medicine (GIM) ambulatory clinic, which has 50,000 patient visits annually. STRATEGIES FOR IMPROVEMENT: For four key elements--physicians as leaders, prevention and primary care, patient access, and innovation and team work--we planned and implemented continuous improvement based on three questions: What were we trying to accomplish? What can we change that would lead to an improvement? How would we know a change is an improvement? EXAMPLE: Prevention and Primary Care. In our primary care setting, an appropriate clinical process to improve would include preventive medicine, specifically Pap-smear performance. In our partnership with the department of obstetrics/gynecology, GIM physicians wanted to improve the rate of adequate Pap smears. To reduce variation in the rates with which physicians collected specimens that were adequate for cytologic examination, the team recommended use of a specific tool, a cervi-brush, which should be more effective in producing adequate specimens. As cervi-brush use increased, rates of inadequate Pap smears dropped from 20%-25% in 1989 to less than 10% for the first six months of 1991. CONCLUSIONS: By focusing attention and resources on a limited number of improvement teams, our initial success built enthusiasm and commitment within GIM and accelerated changes that were incorporated into strategic planning for the Henry Ford Health System as a whole.
Female↗