Higher local carotid artery strain has previously been shown to be a characteristic of unstable c... more Higher local carotid artery strain has previously been shown to be a characteristic of unstable carotid plaques. These plaques may be characterized by microvascular changes that predispose to intraplaque hemorrhage, increasing the likelihood of embolization. Little is known however, about how these strain indices correspond with imaging markers of brain health and metrics of brain structure. White matter hyperintensities (WMHs), which are bright regions seen on T2-weighted brain MRI imaging, are postulated to result from cumulative ischemic vascular injury. Consequently, we hypothesized that plaques that are more prone to microvascular changes and embolization, represented by higher strain indices on ultrasound, would be associated with an increased amount of WMH lesion volume. This relationship would suggest not only emboli as a cause for the brain degenerative changes, but more importantly, a common microvascular etiology for large and small vessel contributions to this process. Subjects scheduled to undergo a carotid endarterectomy were recruited from a neurosurgery clinic. Prior to surgery, participating subjects underwent both ultrasound strain imaging and brain MRI scans as part of a larger clinical study on vascular health and cognition. A linear regression found that maximum absolute strain and peak to peak strain in the surgical side carotid artery were predictive of WMH burden. Furthermore, the occurrence of microembolic signals monitored using transcranial Doppler (TCD) ultrasound examinations also correlated with increasing lesion burden. It is becoming increasingly recognized that cognitive decline is often multifactorial in nature. One contributing extra-brain factor may be changes in the microvasculature that produce unstable carotid artery plaques. In this study, we have shown that higher strain indices in carotid artery plaques are significantly associated with an increased WMH burden, a marker of vascular mediated brain damage.
Resveratrol, a stilbene formed in many plants in response to various stressors, elicits multiple ... more Resveratrol, a stilbene formed in many plants in response to various stressors, elicits multiple beneficial effects in vertebrates. Particularly, resveratrol was shown to have therapeutic properties in cancer, atherosclerosis and neurodegeneration. Resveratrol-induced benefits are modulated by multiple synergistic pathways that control oxidative stress, inflammation and cell death. Despite the lack of a definitive mechanism, both in vivo and in vitro studies suggest that resveratrol can induce a neuroprotective state when administered acutely or prior to experimental injury to the CNS. In this review, we discuss the neuroprotective potential of resveratrol in stroke, traumatic brain injury and spinal cord injury, with a focus on the molecular pathways responsible for this protection.
Middle cerebral artery occlusion (MCAO) by endovascular suture has gained increasing acceptance b... more Middle cerebral artery occlusion (MCAO) by endovascular suture has gained increasing acceptance because it is relatively non-invasive and allows reperfusion. However, its application in rats has resulted in inconsistent infarction volumes which involve only the subcortex or subcortex plus some cortex. In order to eliminate this drawback, we applied the intraluminal suture occlusion of MCA to gerbils that have an incomplete Circle of Willis. MCAO was induced by inserting an endovascular 5-0 nylon suture with a blunted tip into the Circle of Willis. Animals were divided into two groups: permanent MCAO for 24 h (n = 8) and transient MCAO for 3 h with 21 h reperfusion (n = 8). The corrected infarction volume in the permanent MCAO group was 232 +/- 37 mm3 whereas it was 230 +/- 45 mm3 in the transient MCAO group. All animals in both groups had infarction in both cortex and subcortex. Results of this study show that endovascular suture occlusion of MCA can be easily applied in gerbils to ...
The Journal of neuroscience : the official journal of the Society for Neuroscience, 2015
The demyelinating disease multiple sclerosis (MS) has an early inflammatory phase followed by an ... more The demyelinating disease multiple sclerosis (MS) has an early inflammatory phase followed by an incurable progressive phase with subdued inflammation and poorly understood neurodegenerative mechanism. In this study, we identified various parallelisms between progressive MS and the dysmyelinating mouse model Shiverer and then genetically deleted a major neuron-specific mitochondrial anchoring protein Syntaphilin (SNPH) from the mouse. Prevailing evidence suggests that deletion of SNPH is harmful in demyelination. Surprisingly, SNPH deletion produces striking benefits in the Shiverer by prolonging survival, reducing cerebellar damage, suppressing oxidative stress, and improving mitochondrial health. In contrast, SNPH deletion does not benefit clinical symptoms in experimental autoimmune encephalomyelitis (EAE), a model for early-phase MS. We propose that deleting mitochondrial anchoring is a novel, specific treatment for progressive MS.
Conference proceedings : ... Annual International Conference of the IEEE Engineering in Medicine and Biology Society. IEEE Engineering in Medicine and Biology Society. Annual Conference, 2014
Carotid plaque prone to release emboli may be predicted by increased strain variations within pla... more Carotid plaque prone to release emboli may be predicted by increased strain variations within plaque due to arterial pulsation over a cardiac cycle. Non-invasive ultrasound strain imaging may therefore be a viable surrogate to determine the risk of embolic stroke and possible cognitive impairment. Ultrasound strain imaging was performed on 24 human subjects with significant plaque, who also underwent standardized cognitive assessment (Repeatable Battery for the Assessment of Neuropsychological Status (RBANS)) prior to a carotid endarterectomy (CEA) procedure. Radiofrequency signals were acquired using a Siemens Antares with a VFX 13-5 linear array transducer. Plaque regions were segmented by a radiologist at end-diastole using the Medical Imaging Interaction Toolkit. A hierarchical block-matching motion tracking algorithm was utilized to estimate the cumulated axial, lateral, and shear strains within the imaging plane. The maximum strain indices of the plaque, defined as mean accumu...
Stroke secondary to atherosclerosis is one of the most common causes of death in the United State... more Stroke secondary to atherosclerosis is one of the most common causes of death in the United States. A major cause of thromboembolic stroke is atherosclerotic narrowing and ulceration in the region of the carotid bifurcation. The indication for carotid surgery may or may not include the presence of symptoms, but all indications include the presence of an atherosclerotic plaque that may result in embolic or occlusive disease. Because the protective results of surgery depend on accurately defining the presence of these plaques and the degree of carotid artery stenosis, it is essential to understand the diagnostic methods used in determining carotid disease and grading carotid artery stenosis. An understanding of their reliability and associated risks is essential for the proper management of patients with carotid bifurcation disease.
In models of middle cerebral artery occlusion using intraluminal suture, the size and the distrib... more In models of middle cerebral artery occlusion using intraluminal suture, the size and the distribution of ischemic injury vary considerably among laboratories. In transcranial models of cerebral ischemia, a more consistent cerebral ischemic lesion is seen in Spontaneously Hypertensive rats (SHR). In the present study, we performed intraluminal suture occlusion of the MCA in SHR and compared its reproducibility with those in Sprague-Dawley (SD) rats. Male SHR and SD rats were anesthetized with halothane and subjected to 2 h of temporary middle cerebral artery occlusion by an intraluminal suture. Comparisons of regional cerebral blood flow figures taken throughout the experiment and lesion volume figures taken at 24 h after occlusion were made between the two groups. Total lesion volume in the SHR group was 263.6+/-30.5 mm3 (mean +/- SD), significantly larger and less variable than that in the SD group (145.4+/-123.7 mm3, p < 0.02). Throughout the ischemic period there was a tenden...
Twenty severely brain-injured patients with Glasgow Coma Scale scores of 4-9 were prospectively r... more Twenty severely brain-injured patients with Glasgow Coma Scale scores of 4-9 were prospectively randomized to receive one of two standard amino acid formulas, starting with the first day of hospital admission up to day 14 postinjury. Formula 2 (patient group 2) had 54 percent more leucine, 53 percent more isoleucine, 74 percent more valine, 28 percent less phenylalanine, 31 percent less methionine, 111 percent more proline, 38 percent less alanine, and 38 percent less glycine than formula 1 (patient group 1). Groups 1 and 2 received statistically equal overall mean parenteral nutrition calories and protein (2173 +/- 147 vs. 2059 +/- 143 kcal, and 77 +/- 12 vs. 83.1 +/- 6 g, respectively). There was a significant difference in overall mean urinary urea nitrogen excretion (group 1 = 24.6 +/- 1.3 vs. group 2 = 18.3 +/- 1.1, p = 0.02) and nitrogen balance (group 1 = -8.0 +/- 2.1 vs. group 2 = +1.8 +/- 1.2, p = 0.01). Mean overall isoleucine values were significantly higher in group 2 (o...
Ornithine decarboxylase (ODC) activity, the first and generally rate-limiting enzyme for polyamin... more Ornithine decarboxylase (ODC) activity, the first and generally rate-limiting enzyme for polyamine synthesis, is stimulated in permanent focal cerebral ischaemia in areas of incomplete ischaemia which are developing ischaemic brain oedema. As polyamines are ubiquitous ornithine-derived molecules which are obligatory in cold-induced vasogenic oedema, we studied the effect of transient dense cerebral ischaemia with reperfusion on ischaemic oedema development and ODC activity. Fifty-nine Mongolian gerbils were anaesthetized with ketamine hydrochloride (160 mg/kg i.p. plus supplementation as needed). Both common carotid arteries were isolated and a tracheotomy placed in position. EEG was monitored with needle electrodes and temperature maintained at 37-38 degrees C. Twenty-nine gerbils underwent 40 min of bilateral carotid artery occlusion followed by reperfusion times of 10 min, 1, 2, 4, 6 or 8 h. Non-ischaemic control groups were monitored for equal intervals. At sacrifice, the brain ...
We tested the hypothesis that the increase in polyamines observed after cerebral ischaemia is rel... more We tested the hypothesis that the increase in polyamines observed after cerebral ischaemia is related to deficits in electrocortical function as measured by somatosensory evoked potential (SEP). Adult Mongolian gerbils were anaesthetized with ketamine and prepared for monitoring SEP, cerebral blood flow (CBF) in parietal and frontal regions by H2 clearance, and for bilateral carotid artery occlusion (BCO). Seven animals served as controls and received saline. Another 7 animals were treated with the ornithine decarboxylase inhibitor, difluoromethylornithine (DFMO) (100 mg/kg I.P.) just prior to 40 min BCO followed by 4 h reperfusion. With BCO, both CBF and SEP declined significantly. In control animals, CBF fell from basal 37.8 +/- 4.7 cc/100 g/min to 2.9 +/- 1.2 cc/100 g/min and recovered to 22.7 +/- 3.5 cc/100 g/h over the 4 h reperfusion period. DFMO treatment did not alter this CBF pattern. SEP amplitude declined to 11.3 +/- 3.2% basal during occlusion. DFMO preserved SEP during ...
Normal somatosensory evoked potential (SEP) as well as changes after incomplete cerebral ischaemi... more Normal somatosensory evoked potential (SEP) as well as changes after incomplete cerebral ischaemia following bilateral carotid artery occlusion (BCO) were characterized in the Mongolian gerbil. BCO significantly decreased cerebral blood flow (CBF). Reperfusion CBF at 10 min and 2, 3 and 4 h was significantly below preischaemic control values. BCO decreased SEP amplitude but had no effect on EP-P3 central conduction time. BCO did significantly increase EP-P11 central conduction time. Reperfusion amplitudes at 10 min and 2, 3 and 4 h revealed a significant increase only at 4 h when compared to the ischaemic amplitude. EP-P11 central conduction time at 10 min reperfusion showed dramatic improvement compared to ischaemic values, although values at 2, 3 and 4 h reperfusion were not statistically different from ischaemic values. A separate group of animals prepared identically but without BCO showed no significant changes in either SEP or CBF over time. These studies establish the protoco...
Intravenous ciprofloxacin and ceftazidime were compared for efficacy in the treatment of nosocomi... more Intravenous ciprofloxacin and ceftazidime were compared for efficacy in the treatment of nosocomial pneumonia and urinary tract infection (UTI). Patients with nosocomial pneumonia were randomized to receive ciprofloxacin (as the lactate salt) 300 mg i.v. every 12 hours or ceftazidime (with sodium carbonate) 2 g i.v. every eight hours. Patients with UTI were randomized to receive ciprofloxacin 200 mg i.v. every 12 hours or ceftazidime 1 g i.v. every eight hours. Sputum and urine specimens were collected before, during, and after therapy. For patients with pneumonia, the organisms most frequently isolated before treatment began were Escherichia coli, Haemophilus influenzae, Klebsiella pneumoniae, and Proteus mirabilis. Of the 17 pneumonia patients who completed ciprofloxacin treatment, 15 (88%) had resolution of signs and symptoms or improvement. Of the 15 ceftazidime-treated pneumonia patients, 13 (87%) had resolution or improvement. Staphylococcus aureus, Streptococcus species, Acin...
Hyperglycemia increases cerebral damage after transient cerebral ischemia. This study used in viv... more Hyperglycemia increases cerebral damage after transient cerebral ischemia. This study used in vivo 31P nuclear magnetic resonance spectroscopy to determine the relationship of intracellular tissue acidosis and delayed recovery of brain high-energy phosphates to increased damage during the reperfusion period. Mongolian gerbils were subjected to transient bilateral carotid ischemia for 20 min with 2 h reperfusion. All gerbils were pretreated intraperitoneally with equivalent volumes in saline of 0.003 units per kilogram of insulin or vehicle, or with 4 grams of glucose per kilogram. The gerbils were then scanned in a 4.7 Tesla Magnetic Resonance Imager-Spectrometer to determine levels of intracellular pH, inorganic phosphate, adenosine triphosphate, and phosphocreatine. In each group, intracellular pH decreased with ischemia, but most significantly in hyperglycemic animals (6.45 +/- 0.15), in which it had not recovered to preischemic levels by the end of the reperfusion period (6.8 +/...
Higher local carotid artery strain has previously been shown to be a characteristic of unstable c... more Higher local carotid artery strain has previously been shown to be a characteristic of unstable carotid plaques. These plaques may be characterized by microvascular changes that predispose to intraplaque hemorrhage, increasing the likelihood of embolization. Little is known however, about how these strain indices correspond with imaging markers of brain health and metrics of brain structure. White matter hyperintensities (WMHs), which are bright regions seen on T2-weighted brain MRI imaging, are postulated to result from cumulative ischemic vascular injury. Consequently, we hypothesized that plaques that are more prone to microvascular changes and embolization, represented by higher strain indices on ultrasound, would be associated with an increased amount of WMH lesion volume. This relationship would suggest not only emboli as a cause for the brain degenerative changes, but more importantly, a common microvascular etiology for large and small vessel contributions to this process. Subjects scheduled to undergo a carotid endarterectomy were recruited from a neurosurgery clinic. Prior to surgery, participating subjects underwent both ultrasound strain imaging and brain MRI scans as part of a larger clinical study on vascular health and cognition. A linear regression found that maximum absolute strain and peak to peak strain in the surgical side carotid artery were predictive of WMH burden. Furthermore, the occurrence of microembolic signals monitored using transcranial Doppler (TCD) ultrasound examinations also correlated with increasing lesion burden. It is becoming increasingly recognized that cognitive decline is often multifactorial in nature. One contributing extra-brain factor may be changes in the microvasculature that produce unstable carotid artery plaques. In this study, we have shown that higher strain indices in carotid artery plaques are significantly associated with an increased WMH burden, a marker of vascular mediated brain damage.
Resveratrol, a stilbene formed in many plants in response to various stressors, elicits multiple ... more Resveratrol, a stilbene formed in many plants in response to various stressors, elicits multiple beneficial effects in vertebrates. Particularly, resveratrol was shown to have therapeutic properties in cancer, atherosclerosis and neurodegeneration. Resveratrol-induced benefits are modulated by multiple synergistic pathways that control oxidative stress, inflammation and cell death. Despite the lack of a definitive mechanism, both in vivo and in vitro studies suggest that resveratrol can induce a neuroprotective state when administered acutely or prior to experimental injury to the CNS. In this review, we discuss the neuroprotective potential of resveratrol in stroke, traumatic brain injury and spinal cord injury, with a focus on the molecular pathways responsible for this protection.
Middle cerebral artery occlusion (MCAO) by endovascular suture has gained increasing acceptance b... more Middle cerebral artery occlusion (MCAO) by endovascular suture has gained increasing acceptance because it is relatively non-invasive and allows reperfusion. However, its application in rats has resulted in inconsistent infarction volumes which involve only the subcortex or subcortex plus some cortex. In order to eliminate this drawback, we applied the intraluminal suture occlusion of MCA to gerbils that have an incomplete Circle of Willis. MCAO was induced by inserting an endovascular 5-0 nylon suture with a blunted tip into the Circle of Willis. Animals were divided into two groups: permanent MCAO for 24 h (n = 8) and transient MCAO for 3 h with 21 h reperfusion (n = 8). The corrected infarction volume in the permanent MCAO group was 232 +/- 37 mm3 whereas it was 230 +/- 45 mm3 in the transient MCAO group. All animals in both groups had infarction in both cortex and subcortex. Results of this study show that endovascular suture occlusion of MCA can be easily applied in gerbils to ...
The Journal of neuroscience : the official journal of the Society for Neuroscience, 2015
The demyelinating disease multiple sclerosis (MS) has an early inflammatory phase followed by an ... more The demyelinating disease multiple sclerosis (MS) has an early inflammatory phase followed by an incurable progressive phase with subdued inflammation and poorly understood neurodegenerative mechanism. In this study, we identified various parallelisms between progressive MS and the dysmyelinating mouse model Shiverer and then genetically deleted a major neuron-specific mitochondrial anchoring protein Syntaphilin (SNPH) from the mouse. Prevailing evidence suggests that deletion of SNPH is harmful in demyelination. Surprisingly, SNPH deletion produces striking benefits in the Shiverer by prolonging survival, reducing cerebellar damage, suppressing oxidative stress, and improving mitochondrial health. In contrast, SNPH deletion does not benefit clinical symptoms in experimental autoimmune encephalomyelitis (EAE), a model for early-phase MS. We propose that deleting mitochondrial anchoring is a novel, specific treatment for progressive MS.
Conference proceedings : ... Annual International Conference of the IEEE Engineering in Medicine and Biology Society. IEEE Engineering in Medicine and Biology Society. Annual Conference, 2014
Carotid plaque prone to release emboli may be predicted by increased strain variations within pla... more Carotid plaque prone to release emboli may be predicted by increased strain variations within plaque due to arterial pulsation over a cardiac cycle. Non-invasive ultrasound strain imaging may therefore be a viable surrogate to determine the risk of embolic stroke and possible cognitive impairment. Ultrasound strain imaging was performed on 24 human subjects with significant plaque, who also underwent standardized cognitive assessment (Repeatable Battery for the Assessment of Neuropsychological Status (RBANS)) prior to a carotid endarterectomy (CEA) procedure. Radiofrequency signals were acquired using a Siemens Antares with a VFX 13-5 linear array transducer. Plaque regions were segmented by a radiologist at end-diastole using the Medical Imaging Interaction Toolkit. A hierarchical block-matching motion tracking algorithm was utilized to estimate the cumulated axial, lateral, and shear strains within the imaging plane. The maximum strain indices of the plaque, defined as mean accumu...
Stroke secondary to atherosclerosis is one of the most common causes of death in the United State... more Stroke secondary to atherosclerosis is one of the most common causes of death in the United States. A major cause of thromboembolic stroke is atherosclerotic narrowing and ulceration in the region of the carotid bifurcation. The indication for carotid surgery may or may not include the presence of symptoms, but all indications include the presence of an atherosclerotic plaque that may result in embolic or occlusive disease. Because the protective results of surgery depend on accurately defining the presence of these plaques and the degree of carotid artery stenosis, it is essential to understand the diagnostic methods used in determining carotid disease and grading carotid artery stenosis. An understanding of their reliability and associated risks is essential for the proper management of patients with carotid bifurcation disease.
In models of middle cerebral artery occlusion using intraluminal suture, the size and the distrib... more In models of middle cerebral artery occlusion using intraluminal suture, the size and the distribution of ischemic injury vary considerably among laboratories. In transcranial models of cerebral ischemia, a more consistent cerebral ischemic lesion is seen in Spontaneously Hypertensive rats (SHR). In the present study, we performed intraluminal suture occlusion of the MCA in SHR and compared its reproducibility with those in Sprague-Dawley (SD) rats. Male SHR and SD rats were anesthetized with halothane and subjected to 2 h of temporary middle cerebral artery occlusion by an intraluminal suture. Comparisons of regional cerebral blood flow figures taken throughout the experiment and lesion volume figures taken at 24 h after occlusion were made between the two groups. Total lesion volume in the SHR group was 263.6+/-30.5 mm3 (mean +/- SD), significantly larger and less variable than that in the SD group (145.4+/-123.7 mm3, p < 0.02). Throughout the ischemic period there was a tenden...
Twenty severely brain-injured patients with Glasgow Coma Scale scores of 4-9 were prospectively r... more Twenty severely brain-injured patients with Glasgow Coma Scale scores of 4-9 were prospectively randomized to receive one of two standard amino acid formulas, starting with the first day of hospital admission up to day 14 postinjury. Formula 2 (patient group 2) had 54 percent more leucine, 53 percent more isoleucine, 74 percent more valine, 28 percent less phenylalanine, 31 percent less methionine, 111 percent more proline, 38 percent less alanine, and 38 percent less glycine than formula 1 (patient group 1). Groups 1 and 2 received statistically equal overall mean parenteral nutrition calories and protein (2173 +/- 147 vs. 2059 +/- 143 kcal, and 77 +/- 12 vs. 83.1 +/- 6 g, respectively). There was a significant difference in overall mean urinary urea nitrogen excretion (group 1 = 24.6 +/- 1.3 vs. group 2 = 18.3 +/- 1.1, p = 0.02) and nitrogen balance (group 1 = -8.0 +/- 2.1 vs. group 2 = +1.8 +/- 1.2, p = 0.01). Mean overall isoleucine values were significantly higher in group 2 (o...
Ornithine decarboxylase (ODC) activity, the first and generally rate-limiting enzyme for polyamin... more Ornithine decarboxylase (ODC) activity, the first and generally rate-limiting enzyme for polyamine synthesis, is stimulated in permanent focal cerebral ischaemia in areas of incomplete ischaemia which are developing ischaemic brain oedema. As polyamines are ubiquitous ornithine-derived molecules which are obligatory in cold-induced vasogenic oedema, we studied the effect of transient dense cerebral ischaemia with reperfusion on ischaemic oedema development and ODC activity. Fifty-nine Mongolian gerbils were anaesthetized with ketamine hydrochloride (160 mg/kg i.p. plus supplementation as needed). Both common carotid arteries were isolated and a tracheotomy placed in position. EEG was monitored with needle electrodes and temperature maintained at 37-38 degrees C. Twenty-nine gerbils underwent 40 min of bilateral carotid artery occlusion followed by reperfusion times of 10 min, 1, 2, 4, 6 or 8 h. Non-ischaemic control groups were monitored for equal intervals. At sacrifice, the brain ...
We tested the hypothesis that the increase in polyamines observed after cerebral ischaemia is rel... more We tested the hypothesis that the increase in polyamines observed after cerebral ischaemia is related to deficits in electrocortical function as measured by somatosensory evoked potential (SEP). Adult Mongolian gerbils were anaesthetized with ketamine and prepared for monitoring SEP, cerebral blood flow (CBF) in parietal and frontal regions by H2 clearance, and for bilateral carotid artery occlusion (BCO). Seven animals served as controls and received saline. Another 7 animals were treated with the ornithine decarboxylase inhibitor, difluoromethylornithine (DFMO) (100 mg/kg I.P.) just prior to 40 min BCO followed by 4 h reperfusion. With BCO, both CBF and SEP declined significantly. In control animals, CBF fell from basal 37.8 +/- 4.7 cc/100 g/min to 2.9 +/- 1.2 cc/100 g/min and recovered to 22.7 +/- 3.5 cc/100 g/h over the 4 h reperfusion period. DFMO treatment did not alter this CBF pattern. SEP amplitude declined to 11.3 +/- 3.2% basal during occlusion. DFMO preserved SEP during ...
Normal somatosensory evoked potential (SEP) as well as changes after incomplete cerebral ischaemi... more Normal somatosensory evoked potential (SEP) as well as changes after incomplete cerebral ischaemia following bilateral carotid artery occlusion (BCO) were characterized in the Mongolian gerbil. BCO significantly decreased cerebral blood flow (CBF). Reperfusion CBF at 10 min and 2, 3 and 4 h was significantly below preischaemic control values. BCO decreased SEP amplitude but had no effect on EP-P3 central conduction time. BCO did significantly increase EP-P11 central conduction time. Reperfusion amplitudes at 10 min and 2, 3 and 4 h revealed a significant increase only at 4 h when compared to the ischaemic amplitude. EP-P11 central conduction time at 10 min reperfusion showed dramatic improvement compared to ischaemic values, although values at 2, 3 and 4 h reperfusion were not statistically different from ischaemic values. A separate group of animals prepared identically but without BCO showed no significant changes in either SEP or CBF over time. These studies establish the protoco...
Intravenous ciprofloxacin and ceftazidime were compared for efficacy in the treatment of nosocomi... more Intravenous ciprofloxacin and ceftazidime were compared for efficacy in the treatment of nosocomial pneumonia and urinary tract infection (UTI). Patients with nosocomial pneumonia were randomized to receive ciprofloxacin (as the lactate salt) 300 mg i.v. every 12 hours or ceftazidime (with sodium carbonate) 2 g i.v. every eight hours. Patients with UTI were randomized to receive ciprofloxacin 200 mg i.v. every 12 hours or ceftazidime 1 g i.v. every eight hours. Sputum and urine specimens were collected before, during, and after therapy. For patients with pneumonia, the organisms most frequently isolated before treatment began were Escherichia coli, Haemophilus influenzae, Klebsiella pneumoniae, and Proteus mirabilis. Of the 17 pneumonia patients who completed ciprofloxacin treatment, 15 (88%) had resolution of signs and symptoms or improvement. Of the 15 ceftazidime-treated pneumonia patients, 13 (87%) had resolution or improvement. Staphylococcus aureus, Streptococcus species, Acin...
Hyperglycemia increases cerebral damage after transient cerebral ischemia. This study used in viv... more Hyperglycemia increases cerebral damage after transient cerebral ischemia. This study used in vivo 31P nuclear magnetic resonance spectroscopy to determine the relationship of intracellular tissue acidosis and delayed recovery of brain high-energy phosphates to increased damage during the reperfusion period. Mongolian gerbils were subjected to transient bilateral carotid ischemia for 20 min with 2 h reperfusion. All gerbils were pretreated intraperitoneally with equivalent volumes in saline of 0.003 units per kilogram of insulin or vehicle, or with 4 grams of glucose per kilogram. The gerbils were then scanned in a 4.7 Tesla Magnetic Resonance Imager-Spectrometer to determine levels of intracellular pH, inorganic phosphate, adenosine triphosphate, and phosphocreatine. In each group, intracellular pH decreased with ischemia, but most significantly in hyperglycemic animals (6.45 +/- 0.15), in which it had not recovered to preischemic levels by the end of the reperfusion period (6.8 +/...
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Papers by Robert Dempsey