Biomedical subjects
C Shepherd
Publications and source records attributed to C Shepherd.
Automated control of postoperative hypertension: a prospective, randomized multicenter study.
Hypertension after a cardiac operation is a frequent phenomenon. Complications resulting from this include bleeding, disruption of vascular suture lines, subendocardial ischemia, and possible cerebrovascular accidents. Treatment with sodium nitroprusside has become accepted practice to prevent these complications. To improve control of arterial blood pressure, a closed-loop system for sodium nitroprusside administration was developed. A prospective, randomized multicenter study was carried out postoperatively in 180 cardiac surgical patients to evaluate the performance of this system compared with manual control of infusion. Adherence of mean arterial blood pressure to +/- 10% of the target blood pressure occurred 85% of the time with the automatic system and 61% of the time with manual regulation (p less than 0.0001). With the automatic system, there was less hypertension (9% versus 22%; p less than 0.0001) and hypotension (6% versus 22%; p less than 0.0001). The superior control of hypertension was achieved more rapidly with less requirement for nurse regulation of infusion rate. The superior control of blood pressure resulted in less chest tube drainage in the automatic mode (720 mL versus 840 mL; p less than 0.05).
Endothelium-dependent basilar and aortic vascular responses in normotensive and coarctation hypertensive rats.
The responsiveness of acetylcholine (ACh), nitroglycerin (NG) and norepinephrine (NE) (aorta only) in both basilar arteries (BA) and thoracic aortic (TA) rings from coarctation hypertensive rats (CHR) were studied and compared to their sham-operated normotensive control rats (SNR). The effects of these agents were also evaluated in TA or BA with and without endothelium from naive normotensive rats (NNR). Blood pressure (BP) and plasma renin activity (PRA) of CHR were significantly higher than their time-matched SNR. Endothelium removal from TA of NNR significantly enhanced NE and NG sensitivity and reduced the maximum ACh relaxation. Removal of BA endothelium of NNR abolished ACh-induced relaxation but had no effect on NG-induced relaxation. In BA from CHR at any stage of hypertension studied, the sensitivity and maximum relaxation induced by ACh or NG were not significantly different than their respective time-matched SNR. ACh sensitivity of TA did not change in 1 Day CHR but decreased in 4 and 14 Day CHR. NG sensitivity increased, did not change and decreased in 1, 4 and 14 Day CHR, respectively. NE sensitivity increased in all stages of hypertension. These data suggest that in coarctation-induced hypertension there is a complex progression of events in TA which is modulated by different mechanisms as evidenced by the changes in the effects of NE, ACh and NG at various stages of hypertension. The results also suggest that the vascular endothelium of TA but not of BA may provide an acute protective mechanism to counteract the imbalance created by the increased sensitivity of smooth muscle cells to contractile agonists in the early stage of hypertension. However, persistent hypertension appears to override this mechanism.
Epilepsy in school children with intellectual impairments in Sheffield: the size and nature of the problem and the implications for service provision.
This study analyses the prevalence and nature of epilepsy in all children between the ages of 5 and 16 years of age in the City of Sheffield with mild, moderate or severe intellectual impairments. An overall figure of 18% was obtained with a range of 7% for those with mild to moderate intellectual impairments to 67% for those with severe intellectual impairments and a physical disability. The severity of the epilepsy similarly varied with the most severe being in those with severe intellectual impairments and physical disabilities.
Myalgic encephalomyelitis--is it a real disease?
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Effects of CL 115,347, (+/-)-15-deoxy-16-hydroxy-16-vinyl-PGE2 methyl ester, on cardiovascular responses and plasma catecholamines in pithed stroke-prone spontaneously hypertensive rats during sympathetic stimulation.
The effect of CL 115,347, a topically active antihypertensive PGE2 analog, and PGE2 on changes in blood pressure (BP), heart rate (HR) response and plasma epinephrine (E) and norepinephrine (NE) levels induced by stimulation of the sympathetic spinal cord outflow were studied in pithed stroke-prone spontaneously hypertensive rats (SHRSP). Surgical pithing significantly reduced plasma E but not NE levels suggesting that the sympathoadrenal medullary system differentially affects E and NE release. Sympathetic stimulation of the spinal cord of pithed SHRSP increased HR, BP, plasma E and NE levels. Topically applied CL 115,347 (0.001-0.2 mg/kg) dose-dependently decreased BP, while intravenously infused PGE2 (30 micrograms/kg/min) did not alter BP except for a brief initial drop. Topical application of CL 115,347 (0.1 mg/kg) also inhibited BP responses to sympathetic stimulation without effects on HR or plasma E or NE levels. Intravenous infusion of PGE2 (30 micrograms/kg/min) inhibited both BP and HR responses to spinal cord stimulation but did not alter plasma catecholamine levels. These studies in SHRSP suggest that CL 115,347 and PGE2 modulate cardiovascular responses mainly via postjunctional effects, but act differently on the cardiovascular elements, viz. CL 115,347 acts primarily on blood vessels while PGE2 acts on blood vessels and heart.
Teaching emergency department administration: the in-basket exercise.
Borrowing from formats that have been successfully used in teaching administrators, we developed a limited, time-dependent simulation model, the In-Basket Exercise for teaching emergency department administration. The exercise is designed as an introduction to nonclinical decisions, management communication, and managerial control. Using selected material, and under time constraints, participants are asked to describe the options for several types of administrative items. These options and decisions are then discussed within a group. The In-Basket Exercise has been well received as a simple new tool for teaching emergency department administration where existing methods are generally deficient.
A characterization of emergency medicine.
A Medical Specialty Preference Inventory (MSPI) containing 199 items relating to the practice of medicine was developed through ratings by a national sample of over 1,000 board certified physicians in internal medicine, obstetrics-gynecology, pediatrics, psychiatry, surgery, and family practice. Sixty-one emergency physicians completed the MSPI for emergency medicine. Scores on the emergency medicine characterization were compared with those of the six specialties. Results showed emergency medicine most similar to surgery and least similar to psychiatry, although the similarity to surgery was two standard deviations below the mean overall surgery score. A more extensive and systematic effort to characterize emergency medicine using the MSPI rating system could create a national representative factorial characterization of emergency medicine to be used by medical students and physicians when choosing a specialty.
Synergism between tetracycline and amphotericin B in experimental amoebic meningoencephalitis.
The efficacy of tetracycline and amphotericin B in the treatment of primary amoebic meningoencephalitis was studied by means of a mouse model. The results showed marked synergism between these two drugs. Mice who recieved 50 microgram amphotericin B daily succumbed to the infection with only 28.6% survival compared to 0% in untreated controls. In contrast, survival percentage was increased to 66.7% and 84.6% in mice receiving the combined dosage schedule of 50 microgram amphotericin B with 2 tetracycline, and 50 microgram amphotericin B with 3 mg tetracycline, respectively. The finding of synergism between tetracycline and amphotericin may provide a better means for the treatment of this disease.
Resistance of mice to Naegleria meningoencephalitis transferred by immune serum.
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Phagocytic behaviour towards baker's yeast distinguishes pathogenic from non-pathogenic Naegleria.
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Protective immunity to Naegleria fowleri in experimental amebic meningoencephalitis.
Naegleria fowleri, a free-living ameboflagellate, is the causative organism of primary amebic meningoencephalitis. Intranasal inoculation of N. fowleri in mice produces an infection similar to human disease. Mice immunized with live N. fowleri by intraperitoneal injection were found to be more resistant to subsequent intranasal challenge. These results may provide a lead to the development of immunotherapy for this virulent disease for which satisfactory chemotherapy is presently unavailable.
Growth inhibition of Naegleria fowleri by tetracycline, rifamycin, and miconazole.
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Alzheimer's disease and inflammation: a review of cellular and therapeutic mechanisms.
1. Of the neurodegenerative diseases that cause dementia, Alzheimer's disease (AD) is the most common. Three major pathologies characterize the disease: senile plaques, neurofibrillary tangles and inflammation. We review the literature on events contributing to the inflammation and the treatments thought to target this pathology. 2. The senile plaques of AD consist primarily of complexes of the beta-amyloid protein. This protein is central to the pathogenesis of the disease. 3. Inflammatory microglia are consistently associated with senile plaques in AD, although the classic inflammatory response (immunoglobulin and leucocyte infiltration) is absent. beta-Amyloid fragments appear to mediate such inflammatory mechanisms by activating the complement pathway in a similar fashion to immunoglobulin. 4. Epidemiological studies have identified a reduced risk of AD in patients with arthritis and in leprosy patients treated with anti-inflammatory drugs. Longitudinal studies have shown that the consumption of anti-inflammatory medications reduces the risk of AD only in younger patients (< 75 years). 5. There is a considerable body of in vitro evidence indicating that the inflammatory response of microglial cells is reduced by non-steroidal anti-inflammatory drugs (NSAID). However, no published data are available concerning the effects of these medications on brain pathology in AD. 6. Cyclo-oxygenase 2 enzyme is constitutively expressed in neurons and is up-regulated in degenerative brain regions in AD. Non-steroidal anti-inflammatory drugs may reduce this expression. 7. Platelets are a source of beta-amyloid and increased platelet activation and increased circulating beta-amyloid have been identified in AD. Anti-platelet medication (including NSAID) would prevent such activation and its potentially harmful consequences. 8. Increased levels of luminal beta-amyloid permeabilizes the blood-brain barrier (BBB) and increases vasoconstriction of arterial vessels, paralleling the alterations observed with infection and inflammation. Cerebral amyloidosis is highly prevalent in AD, compromising the BBB and vasoactivity. Anti-inflammatory medications may alleviate these problems.
Severe co-trimoxazole reaction in a man with AIDS.
Although other drugs can be used in the prophylaxis and treatment of HIV-infected persons, family physicians will prescribe co-trimoxazole frequently. These providers need to recognize the overall increased frequency of adverse reactions to this drug in this population and the potential for severe hypersensitivity effects requiring intensive hospital care. While the exact importance re-exposure has in causing this reaction remains unclear, certainly providers must pay particular attention to patients who have had any earlier sensitivity to the drug before treatment is resumed. Desensitization therapy has been used successfully in some HIV-positive individuals, even after severe reactions; however, this case again teaches the need for prudence in the use of all pharmacological agents.