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Biomedical subjects

R G Williams

Publications and source records attributed to R G Williams.

At least 19 recordsLinked to original sources

c-fos expression in isolated rat spinal cord.

Expression of c-fos-immunoreactivity (c-fos-ir) has been demonstrated in the dorsal horn of lumbar segments of an isolated spinal cord preparation from 3 week old rats. The method of preparation generated a low level of c-fos-ir activity which was not significantly altered by low intensity (1.5 times threshold) dorsal root stimulation, but was significantly increased by high intensity (20 times threshold) stimulation. Replacement of the calcium in the bathing medium by 2 mM manganese suppressed all detectable c-fos-ir, whereas inclusion of 0.5 microM capsaicin caused intense c-fos-ir expression in the absence of stimulation. The number of dorsal horn cells exhibiting c-fos-ir increased between 0.5 and 1 h after stimulation, reaching a maximum at 2 h, with no further increase at longer intervals. Few positive cells were found when the incubation temperature was reduced from 27 to 20 degrees C. The strongest increase in c-fos-ir was found in the dorsal horn ipsilateral to the stimulated dorsal root and a smaller, but significant, increase was also seen in the contralateral dorsal horn. Cords obtained from animals treated at 1 day old with capsaicin to destroy afferent C fibres showed a reduction in the number of c-fos-ir positive cells induced by high intensity dorsal root stimulation. This preparation will aid detailed investigation of the pharmacology of nociceptive pathways.

Animals

Training pediatricians for the evolving generalist-specialist interface in the managed care era.

Managed care involves the linkage of service delivery and financing. One of the outgrowths of the rapid expansion of managed care over the past decade has been an increasing consensus that the generalist of the future will need to manage more of the patients traditionally cared for by subspecialists. Subspecialty education for pediatric residents becomes increasingly important as the role of the pediatric generalist enlarges to include independent outpatient management of some less complex but traditional subspecialty patients as well as collaborative management of more complex patients. To prepare for this role, a balanced exposure to subspecialty problems in outpatient as well as inpatient settings is required. At the same time, however, the growth of managed care has led to certain barriers for providing this enhanced training. This article describes the effects of managed care on the role and scope of the pediatric subspecialist as well as on educational strategies for coping with these changes while reshaping the roles of both generalists and subspecialists for maximal effectiveness in meeting the health care needs of children.

Academic Medical Centers

Gabapentin, ineffective in normal rats, markedly reduces C-fibre evoked responses after inflammation.

Gabapentin (Neurontin) is a novel anticonvulsant with an as yet unknown mechanism of action. This electrophysiological study investigated the potential antinociceptive actions of systemically administered gabapentin in normal animals and after inflammation induced by the injection of carrageenan. Gabapentin facilitated the noxious evoked responses of dorsal horn neurones recorded in normal animals. In complete contrast, gabapentin strongly and dose-dependently inhibited the C-fibre evoked response and post-discharge, but not the A beta-fibre evoked response, of neurones recorded in animals 3 h after the injection of carrageenan. This unique and selective profile of gabapentin may provide a novel treatment for clinical inflammatory pain states.

Acetates

In vitro response of Escherichia coli to antibiotics and ultrasound at various insonation intensities.

Microbial infections on implanted medical devices are difficult to treat. Application of 70 kHz ultrasonic irradiation to gentamicin treatment greatly enhanced the action of the antibiotic in terms of reduced viable bacterial concentrations. Ultrasonic irradiation was carried out at various insonation intensities that were noninhibitory in the absence of antibiotic. Synergistic killing was observed to be a function of ultrasonic intensity. Greatest killing (approximately 5 log reduction in viable population) was realized at full intensity (4.5 W/cm2), and decreased with reductions in power density. At lowest intensity (10 mW/cm2), no significant acoustic enhanced killing was noted.

Energy Transfer

The effect of medical education on students' patient-satisfaction ratings.

PURPOSE: To determine whether medical students' interpersonal and communication skills, as measured by satisfaction ratings given by standardized patients (SPs), improves or deteriorates with additional training and experience. METHOD: A longitudinal study was made of a single cohort of 133 medical students scheduled to graduate in 1994 from the University of Illinois College of Medicine at Chicago. Clinical performance examinations employing clinical encounters with SPs were given at the end of the students' second year at the end of the first quarter of their fourth year. The second-year examination consisted of four student-SP encounters for each student; the fourth-year examination consisted of 16 such encounters. For each examination, SP perceptions of interpersonal and communication skills were measured using six items from the American Board of Internal Medicine Patient Satisfaction Questionnaire; the items employed five ordinal-scale descriptors (from 1 = poor to 5 = excellent). The unit of analysis was the student-SP encounter. For each year, ratings on each item were averaged across encounters to produce a mean rating for each item; in addition, ratings across all the encounters and items were averaged to produce a mean total patient satisfaction rating. The percentage of fail or poor ratings given for each item was calculated, as was the average of these percentages across the items. All rating calculations were done between years and between genders. Two-tailed, paired t-tests and F-ratios were used for comparisons between years and between genders, respectively. Finally, ratings for a comparison group of first-, second-, and third-year internal medicine residents were gathered under similar testing conditions. RESULTS: Mean total patient satisfaction with the students' clinical performances improved from the first examination (3.51, SD, .84) to the second (3.60, SD, .86). The percentage of student encounters receiving fair or poor ratings decreased from 14.5% in the second year to 12% in the fourth year; resident encounters received a fair or poor rating 7.8% of the time. The female students received fewer fair or poor ratings than did the male students both in their second year (11.7% vs 16%) and in their fourth year (9.3% vs 12.8%). Of the six patient-satisfaction items, both the students and the residents consistently were ranked lowest in encouraging patients to ask questions and answering patient questions. CONCLUSION: Contrary to the stated beliefs of some physician-educators that students' skills deteriorate during the course of training, these medical students' interpersonal and communication skills improved with additional training and experience.

Communication

Usefulness of banding of the pulmonary trunk with single ventricle physiology at risk for subaortic obstruction.

This study addresses the effects of early banding of the pulmonary trunk and subsequent management of subaortic obstruction on the attainment of acceptable pre-Fontan hemodynamics in patients with a single left ventricle and aorta arising from an outflow chamber. We report our experience with 26 patients seen at our institution between January 1984 and December 1994 with a diagnosis of double-inlet left ventricle or tricuspid atresia and transposed great arteries, who were initially managed with pulmonary artery banding in the first 6 months of life. Pulmonary artery band placement was performed at an age of 2.1 +/- 1.8 months (mean +/- SD). Associated aortic arch abnormalities were present in 8 patients (31%). There were 19 patients (73%) who underwent treatment with a Damus-Kaye-Stansel procedure or ventricular septal defect (VSD) enlargement for a significant subaortic gradient or morphologically small VSD, alone or in conjunction with a Glenn or Fontan procedure. Eighteen of 26 patients (69%) underwent cardiac catheterization to assess their candidacy for the Fontan operation. Of this group, 16 were classified as low to moderate risk and 2 as high-risk Fontan candidates, based on hemodynamic criteria. The cumulative mortality for the entire cohort was 19%. Our results suggest that this high-risk group of patients can undergo effective pulmonary artery banding as an initial palliative step, with subsequent intervention for subaortic ob- struction when it is documented or highly suspected, and that acceptable pre-Fontan hemodynamic parameters can be achieved.

Cardiac Catheterization

Does the presence of heparin and dexamethasone in the vitrectomy infusate reduce reproliferation in proliferative vitreoretinopathy?

BACKGROUND: Reproliferation following vitrectomy for proliferative vitreoretinopathy (PVR) causes redetachment in up to 55% of cases. Heparin and corticosteroids have each been shown to inhibit the development of proliferative vitreoretinopathy (PVR) in experimental models. However, little information is available on the use of these agents in humans. METHODS: In this pilot study, 62 eyes of 62 patients with severe PVR requiring vitrectomy were prospectively randomized to receive either BSS Plus (control) or BSS Plus with heparin and dexamethasone (HD) in the infusate. RESULTS: After one operation, the retina was reattached in 42 (71%) of 59 eyes: 22 (65%) of 34 eyes in the control group and 20 (80%) of 25 eyes in the HD group (P = 0.16). Reproliferation developed in 26.5% of the control group (9 of 34 eyes) and 16% of the HD group (4 of 25 eyes; P = 0.26). Postoperative hemorrhage was significantly more frequent in the HD group (P = 0.02) but did not influence final visual or anatomic outcome. Hypotony was less frequent in the HD group but the difference was not significant (P = 0.063). CONCLUSION: The trend from this randomized pilot study suggests that HD supplementation of the vitrectomy infusate may reduce the reproliferation rate in PVR and possibly reduce the rate of hypotony. Postoperative hemorrhage was more frequent with HD but did not cause redetachment or alter visual outcome. A multicenter trial involving more patients would be required to better evaluate the efficacy of HD as a pharmacologic adjunct to PVR surgery.

Adolescent

The antiepileptic agent gabapentin (Neurontin) possesses anxiolytic-like and antinociceptive actions that are reversed by D-serine.

This report describes the activity of the antiepileptic agent gabapentin (Neurontin) in animal models predictive of anxiolysis and analgesia. Gabapentin displayed anxiolytic-like action in the rat conflict test, the mouse light/dark box and the rat elevated X-maze with respective minimum effective doses (MEDs) of 3, 10 and 30 mg/kg. Furthermore, gabapentin also induced behavioural changes suggestive of anxiolysis in the marmoset human threat test with a MED of 30 mg/kg. In the rat formalin test of tonic nociception, gabapentin dose-dependently (30-300 mg/kg) and selectively blocked the late phase with a MED of 100 mg/kg. However, it failed to block carrageenan-induced paw oedema. The intracerebroventricular (ICV) administration of the glycine/NMDA receptor agonist D-Serine, dose-dependently (10-100 micrograms/animal) reversed the antinociceptive action of gabapentin (200 mg/kg, SC). D-Serine (30 micrograms/animal, ICV) also reversed the anxiolytic-like effects (in the light/dark box and the rat elevated X-maze) of gabapentin (30 mg/kg). In contrast, L-Serine (100 micrograms, ICV) failed to block the antinociceptive action of gabapentin. The antinociceptive action of (+)-HA-966 (25 mg/kg, SC), a partial agonist at the glycine/NMDA receptor, was reversed by D-Serine (100 micrograms/animal, ICV). However, D-Serine (100 micrograms/animal, ICV) failed to affect the antinociceptive action of a competitive NMDA receptor antagonist CGS 19755 (3 mg/kg, SC). Gabapentin has negligible affinity for the strychnine insensitive [3H]glycine binding site. This indicates that the interaction between gabapentin and D-Serine may not involve the NMDA receptor complex. Gabapentin may represent a novel type of anxiolytic and analgesic agent.

Acetates

NADPH diaphorase activity in peptidergic neurones of the parasitic nematode, Ascaris suum.

The histochemical marker for nitric oxide synthase, NADPH diaphorase, is known to co-localize in mammalian neurones with various classical neurotransmitters and neuropeptides. The nervous system of the parasitic nematode Ascaris suum has previously been shown to contain both NADPH diaphorase activity and neuropeptide immunoreactivity. This study examined the possibility that NADPH diaphorase and neuropeptide immunoreactivity may co-exist in the same neurones. Two antisera were used, one raised to KYSALMFamide, a C-terminal synthetic analogue of SALMFamide 1 (GFNSALMFamide), and another that recognizes calcitonin-gene-related peptide (CGRP). We provide evidence that in a distinct subset of neurones in the ventral, dorsal and lateral ganglia NADPH diaphorase staining and SALMFamide-like immunoreactivity are co-localized, suggesting a possible role for nitric oxide in modulating neuropeptide activity in these regions. CGRP-like immunoreactivity was less widely distributed, and was not consistently co-localized with NADPH diaphorase.

Animals

Pathophysiology and treatment of cocaine toxicity: implications for the heart and cardiovascular system.

OBJECTIVE: To review the data on pharmacology, pathophysiology and treatment of cocaine toxicity, with particular relevance to the heart and cardiovascular system. DATA SOURCE AND STUDY SELECTION: Published epidemiology, laboratory and clinical studies on the pharmacology, electrophysiology and pathophysiology of cocaine toxicity and its treatment. MAIN RESULTS: Cocaine toxicity-related morbidity and mortality are frequent due to the potent pharmacological effects of the drug as an indirect-acting sympathomimetic agent and its class I antiarrhythmic property paradoxically inducing pro-arrhythmia. The cardiac and cardiovascular toxic effects of cocaine include various degrees of myocardial ischemia, cardiac arrhythmias, cardiotoxicity, hypertensive effects, cerebrovascular effects and a hypercoagulable state. Treatment of cocaine toxicity must be based on the multiple factors leading to the toxicity. Sodium bicarbonate appears to have an important role in the acute setting with conduction abnormalities, seizures or acidosis. Unopposed alpha-stimulation provided by beta-blockade should be avoided. Central nervous system hyperexcitability should be treated with diazepam. The use of calcium antagonists appears logical. CONCLUSION: Cocaine is an alkaloid with widespread illicit use. The rationale for treating acute cocaine intoxication has become clearer and more logical with increased knowledge of its mechanisms of action.

Arrhythmias, Cardiac

Anomalous origin of the left main pulmonary artery from the ascending aorta associated with DiGeorge syndrome.

We place on record 2 infants with the DiGeorge syndrome and anomalous origin of the left pulmonary artery from the ascending aorta. We postulate that: (1) embryogenesis of anomalous origin of the left pulmonary artery from the ascending aorta might be due to the persistent fifth aortic arch connecting both arterial systems; (2) an anomalous pulmonary artery arising from the ascending aorta is part of the aortic arch abnormality accompanied by normal conotruncal septation; and (3) in the DiGeorge syndrome, cardiac anomalies that originate from the conotruncus or aortic arch, or both, may have the same embryologic mechanisms.

Aorta

Factors influencing survival in patients undergoing the bidirectional Glenn anastomosis.

The bidirectional Glenn anastomosis (BGA) has long been used as a surgical intervention for patients with single ventricle physiology. Initially, this procedure was the final stage in palliation and was performed in older children. Eventually, as the Fontan procedure came to be used as a method to separate circulations, the Glenn procedure was performed as an intermediate step. Over time, the BGA was performed as an alternative for patients who were considered to be at high risk with the Fontan procedure. Between January 1, 1988, and January 1, 1994, 129 patients underwent BGA at the University of California-Los Angeles. These patients were reviewed retrospectively, including clinic visits, catheterization, and echocardiographic information. The overall survival rate was 87% (112 of 129 patients). The average length of follow-up was 27 months. This information was then analyzed by univariate and multivariate analysis. Several factors were related to failure in patients who underwent BGA including pulmonary artery pressure, systemic right ventricle, and presence of anomolous pulmonary venous drainage and heterotaxy syndrome.

Adolescent