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Biomedical subjects

M Rizzo

Publications and source records attributed to M Rizzo.

At least 109 records · Page 6Linked to original sources

Estrogen blocks M-CSF gene expression and osteoclast formation by regulating phosphorylation of Egr-1 and its interaction with Sp-1.

Central to the pathogenesis of osteoporosis is the ability of estrogen deficiency to increase osteoclast formation by enhancing stromal cell production of the osteoclastogenic cytokine macrophage colony-stimulating factor (M-CSF). We report that stromal cells from ovariectomized mice exhibit increased casein kinase II-dependent phosphorylation of the nuclear protein Egr-1. Phosphorylated Egr-1 binds less avidly to the transcriptional activator Sp-1 and the resulting higher levels of free Sp-1 stimulate transactivation of the M-CSF gene. Estrogen replacement fails to block M-CSF mRNA expression and osteoclast formation in ovariectomized mice lacking Egr-1, confirming the critical role played by this transcription factor in mediating the antiosteoclastogenic effects of estrogen. Thus, by downregulating formation of a novel Egr-1/Sp-1 complex in stromal cells, estrogen deficiency results in enhanced levels of free Sp-1 and increased M-CSF gene expression and osteoclast formation.

Animals↗

High-performance liquid chromatographic determination of new 2,3-benzodiazepines.

A simple high-performance liquid chromatographic assay with ultraviolet detection at 254 nm for simultaneous determination of 2,3-benzodiazepine derivatives (2,3-BZ2 and 2,3-BZ2Me) and their metabolites in rat plasma is described. The procedure involves a fast extraction of the drugs from the buffered sample using methanol. The extract is evaporated to dryness at 45 degrees C and the residue is redissolved in methanol (twice). A 20-microl aliquot is injected into the liquid chromatograph and eluted with methanol-water (65:35, v/v) on a C18 reversed-phase column. At a flow-rate of 1.5 ml/min the detection time was 3.1 min for 2,3-BZ2, 5.06 min for 2,3-BZ2Me and 10.9 min for prazepam, used as internal standard for the quantification of the studied compounds. The method has been used to investigate the steady-state concentrations of two 2,3-benzodiazepine derivatives in Sprague-Dawley rat plasma.

Animals↗

Thrombolysis in Myocardial Infarction frame count in saphenous vein grafts.

BACKGROUND: Although the Thrombolysis in Myocardial Infarction flow grade system is a widely used index of coronary blood flow, it has important limitations. We recently described a new continuous measure of blood flow in native coronary arteries, the Thrombolysis in Myocardial Infarction frame count (TFC), and sought to extend this method to coronary artery bypass grafts. METHODS: We retrospectively analyzed cinefilms of patients' status after coronary artery bypass grafting, excluding patients with recent myocardial infarction and grafts with stenoses in the graft or native vessel. We counted the cineframes required for dye to travel from the ostium of the graft to the graft anastomotic site (TFCg) and to a standardized distal coronary landmark (TFC). RESULTS: For all vein grafts combined, TFCg was 19.2+/-5.7 frames (mean+/-SD, n = 93) and the TFC was 33.9+/-8.0 frames (n = 67). The upper limits for "normal" flow, calculated from the 95% confidence intervals, were 31 frames for TFCg and 50 frames for TFC. CONCLUSIONS: The Thrombolysis in Myocardial Infarction frame counting method has now been extended to normal saphenous vein grafts, and normal reference values are provided.

Cardiac Catheterization↗

Chronic motion perception deficits from midline cerebellar lesions in human.

A selective motion perception deficit is seen in patients with acute midline cerebellar lesions. Patients with more lateralized acute cerebellar damage do not demonstrate such a deficit (Nawrot M, Rizzo M. Vis Res 1995;35:723-731). However, as these patients were tested only between 10 and 14 days post-ictus, the stability of this perceptual deficit into the chronic phase remained undetermined. The current study extends the previous findings by showing that the motion perception deficit caused by mid-line cerebellar lesions remains permanent at least 2 years into the chronic phase. The extent and longevity of this deficit resembles that of the well known motion-blind patient LM who has a large cerebellar lesion in addition to her extensive cortical damage. Again, we propose that the mid-line cerebellar damage may produce a severe motion perception deficit by disruption the visual-motor integration mechanisms involved in perceptual stabilization, even though cortical motion processing mechanisms are unaffected.

Cerebellum↗

Relationship between anticonvulsant activity and plasma level of some 2,3-benzodiazepines in genetically epilepsy-prone rats.

The anticonvulsant effects of some novel 2,3-benzodiazepines acting as alpha-amino-3-hydroxy-5-methyl-isoxazole-4-propionic acid/kainate (AMPA/KA) antagonists were evaluated in genetically epilepsy prone rats. The ED50 values against clonic and tonic seizures (in micromol/kg) revealed that the rank order of anticonvulsant activity was: GYKI 52466 > 2,3BZ-2 > 2,3 MBZ-2 > NBQX. Maximal anticonvulsant protection was observed 15-45 min after the i.p. administration of NBQX and GYKI 52466, 30-90 min after the i.p. administration of 2,3BZ-2, and 45-120 min after the i.p. administration of 2,3MBZ-2. The time course of plasma levels of rats treated with GYKI 52466 showed that peak plasma concentration was observed 15 min after i.p. administration, 2,3BZ-2 revealed that peak plasma concentration was achieved 45 min after i.p. administration, whereas following 2,3MBZ-2 administered i.p., two curves were detected; one is referred to the parent compound and the other to its demethylate metabolite that corresponds to 2,3BZ-2. The therapeutic index (ratio of TD50 values for impaired rotarod performance and ED50 values for anticonvulsant activity) revealed that NBQX and GYKI 52466 were slighly more toxic than 2,3BZ-2 and 2,3MBZ-2. The present data suggest that 2,3-benzodiazepines acting at AMPA/kainate receptors play an important role in the generation and/or propagation of the audiogenic seizures in genetically epilepsy-prone rats.

Animals↗

The Open Artery Hypothesis: Past, Present, and Future.

The survival benefit following a reperfusion strategy, be it pharmacologic or mechanical, appears to be due to both full and early reperfusion. While the TIMI Flow Grade classification scheme has been a useful tool to assess coronary blood flow in acute syndromes, it has several limitations. A newer method of assessing coronary blood flow called the Corrected TIMI Frame Count method has the following advantages: (1) it is a continuous quantitative variable rather than a categorical qualitative variable; (2) the flow in the non-culprit artery is not assumed to be normal as it is in the assessment of TIMI Grade 3 Flow; (3) there is simplified reporting of reperfusion efficacy through the use of a single number instead of expressing the data in 2 to 4 categories; (4) because a single number rather than 4 categories is used to report the data, there is more efficient use of the dataset by increasing the statistical power; and finally (5) coronary flow can be expressed in intuitive terms (e.g. time or cm/sec for strategy A versus time or cm/sec for strategy B). This paper reviews the history of the open artery hypothesis and recent advances in the field.

Journal Article↗

Magnetic resonance imaging data in the evaluation of effects of functional electrical stimulation on knee joints of adolescents with spinal cord injury.

Diagnostic imaging, consisting of roentgenograms and magnetic resonance images (MRIs), was performed as part of an evaluation of the effects of a functional electrical stimulation (FES) program on the knee joints of 29 adolescents with spinal cord injuries following implantation of fine-wire intramuscular electrodes in their lower extremity muscles. The subjects underwent a regimen consisting of stimulated exercise, standing and/or walking. The effects of FES on knee joints were prospectively studied by reviewing diagnostic imaging data. Evaluation of MRIs and plain radiographs showed no evidence of knee joint pathology secondary to FES exercise or weight bearing. In fact, based on follow-up of MRI scan, many of the joints improved following participation in the program. The MRI data supported the clinical examination of the knee joints of these children. Clinical examination appears adequate for screening for potential knee joint problems.

Adolescent↗

Perception of movement and shape in Alzheimer's disease.

Alzheimer's disease is the most prevalent cause of abnormal cognitive decline in older adults and commonly affects visual function. Recent evidence suggests that Alzheimer's disease impairs the processing of visual motion, but these conclusions are based on conflicting results in the few cases studied, and the processing of complex motion images has not been investigated. In the present study of motion processing in Alzheimer's disease we assessed visual functions in 63 adults: 41 with mild to moderate Alzheimer's disease (mean age 72.3 years) and 22 without dementia (mean age 71.7 years). Processing of motion cues was tested with computer animation sequences known as random-dot cinematograms, which resemble the stimuli used to define motion processing deficits in primates with lesions of cortical area MT. Results showed that participants with Alzheimer's disease required significantly greater thresholds for perceiving shapes defined by motion cues compared with participants without dementia (P = 0.0005). There were no significant differences between the two groups (P < 0.05) in static visual acuity, static spatial contrast sensitivity and, surprisingly, dynamic visual acuity, which was normal, and motion direction discrimination, which was relatively spared. We conclude that mild to moderate Alzheimer's disease has significant effects on the perception of structure from motion with relative sparing of motion direction discrimination. We cannot exclude a contribution by retinal pathology, but retinal dysfunction alone cannot explain the pattern of defects we observed. The complex motion image processing deficit we identified is likely to have a cerebral basis and has the potential to affect navigation and the recognition of objects in relative motion, as encountered during walking and automobile driving.

Aged↗

Increased expression of HDJ-2 (heat shock protein 40) and heat shock protein 70 in biopsy specimens of transplanted human lungs.

BACKGROUND: Heat shock proteins are expressed during several forms of stress and inflammation. This study was done to determine whether the expression of heat shock protein HDJ-2 (heat shock protein 40), heat shock protein 60, and heat shock protein 70 are increased during rejection in human pulmonary allografts. METHODS: Thirty-five transbronchial biopsy specimens were obtained from adult lung transplant recipients. Histologic analysis and assessment of heat shock protein HDJ-2, heat shock protein 60, and heat shock protein 70 mRNA expression was performed. Total RNA was extracted, reverse transcribed, and amplified by polymerase chain reaction with oligonucleotide primers specific for the heat shock proteins. The identity of the amplified message was verified by Southern blot and slot blot analysis. RESULTS: The expression of heat shock protein HDJ-2 was significantly higher in samples from lung transplant recipients undergoing rejection when compared with recipients without rejection or infection. Heat shock protein 70 expression was also increased in rejection. Expression of heat shock protein 60 did not show any increase in recipients with no evidence of rejection and infection or transplant recipients with rejection or infection. Serial analysis of heat shock protein HDJ-2 and heat shock protein 70 obtained in biopsy specimens during and after rejection showed a decrease of heat shock protein HDJ-2 and heat shock protein 70 expression after resolution of lung rejection. CONCLUSION: Our data demonstrate that the expression of heat shock protein HDJ-2 and heat shock protein 70 increases during lung rejection. However, only heat shock protein HDJ-2 was able to differentiate between rejection and infection. Measurement of heat shock protein HDJ-2 in transbronchial biopsy specimens may assist in the differential diagnosis between rejection and infection in lung transplant recipients.

Carrier Proteins↗

Dorsal onlay graft urethroplasty using penile skin or buccal mucosa in adult bulbourethral strictures.

PURPOSE: Preputial skin graft is used routinely for urethral reconstruction in patients with stricture disease. Alternative donor sites include extrapenile skin, bladder mucosa and buccal mucosa. Recently buccal mucosa graft has been suggested when local epithelial tissue is not available. We describe our experience with 37 patients undergoing 1-stage correction of bulbar urethral stricture using a penile skin (31) or buccal mucosa (6) graft. MATERIALS AND METHODS: In 37 patients with bulbar urethral strictures a nontubularized dorsal onlay graft was used for urethral reconstruction. A preputial skin graft was used in 31 patients and a buccal mucosa graft in 6 with a paucity of local skin. Buccal mucosa graft length ranged from 2.5 to 5 cm. (average 4) and preputial skin graft was 2.5 to 12 cm. long (average 4.7). A dorsal approach to the urethral lumen was used in all patients who underwent onlay graft urethroplasty. RESULTS: Mean followup was 21.5 months for all 37 patients, 23 months for 31 treated with preputial skin graft and 13.5 months for 6 treated with buccal mucosa graft. The clinical outcomes were considered a failure anytime postoperative instrumentation was needed, including dilatation. In the series 34 cases (92%) were classified as a success and 3 (8%) as failure. CONCLUSIONS: Onlay graft urethroplasty provided excellent results in 92% of adults with bulbourethral stricture. The dorsal approach to the urethra allowed the use of foreskin or buccal mucosa graft for reconstruction of the adequate urethral lumen.

Adult↗

Angioplasty guidewire velocity: a new simple method to calculate absolute coronary blood velocity and flow.

The Thrombolysis In Myocardial Infarction (TIMI) frame count is a relative index of coronary flow that measures time by counting the number of frames required for dye to travel from the ostium to a standardized coronary landmark in a cineangiogram filmed at a known speed (frames/s). We describe a new method to measure distance along arteries so that absolute velocity (length divided by time) and absolute flow (area x velocity) may be calculated in patients undergoing percutaneous transluminal coronary angiography (PTCA). After PTCA, the guidewire tip is placed at the coronary landmark and a Kelly clamp is placed on the guidewire where it exits the Y-adapter. The guidewire tip is then withdrawn to the catheter tip and a second Kelly clamp is placed on the wire where it exits the Y-adapter. The distance between the 2 Kelly clamps outside the body is the distance between the catheter tip and the anatomic landmark inside the body. Velocity (cm/s) may be calculated as this distance (cm) divided by TIMI frame count (frames) x film frame speed (frames/s). Flow (ml/s) may be calculated by multiplying this velocity (cm/s) and the mean cross-sectional lumen area (cm2) along the length of the artery to the TIMI landmark. In 30 patients, velocity increased from 13.9 +/- 8.5 cm/s before to 22.8 +/- 9.3 cm/s after PTCA (p <0.001). Despite TIMI grade 3 flow both before and after PTCA in 18 patients, velocity actually increased 38%, from 17.0 +/- 5.4 to 23.5 +/- 9.0 cm/s (p = 0.01). For all 30 patients, flow doubled from 0.6 +/- 0.4 ml/s before to 1.2 +/- 0.6 ml/s after PTCA (p <0.001). In the 18 patients with TIMI grade 3 flow both before and after PTCA, flow increased 86%, from 0.7 +/- 0.3 to 1.3 +/- 0.6 ml/s (p = 0.001). Distance along coronary arteries (length) can be simply measured using a PTCA guidewire. This length may be combined with the TIMI frame count to calculate measures of absolute velocity and flow that are sensitive to changes in perfusion. TIMI grade 3 flow is composed of a range of velocities and flows.

Angioplasty, Balloon, Coronary↗

Long-term efficacy of alpha-interferon in beta-thalassemics with chronic hepatitis C.

Hepatitis C virus (HCV) infection is a common cause of liver disease among polytransfused thalassemics. We treated a cohort of subjects with beta-thalassemia major and chronic hepatitis C with alpha-interferon. The aims of the study were to assess the long-term biochemical and virologic efficacy of alpha-interferon and to evaluate the influence of HCV type and liver siderosis on the outcome of therapy. Seventy subjects (mean age, 14.1 years) with chronic HCV infection and abnormal aminotransferases received recombinant alpha-interferon for 12 months and were observed after therapy for at least 24 months. Sixty-three subjects (90%) were HCV-RNA positive at the start of therapy. HCV type 1b was found in 41 subjects (65.1%), non-1b types in 13 (20.6%), and mixed HCV types in 9 (14.3%). Liver biopsy showed cirrhosis in 11 subjects (15.7%) and siderosis grade 3-4 in 24 patients (34.2%). Three patients stopped therapy due to adverse events. Twenty-eight subjects (40%) had normal aminotransferases and had cleared HCV-RNA when last observed (mean follow-up, 36.5 months; range, 25 to 49 months). Of 41 patients who did not normalize aminotransferases, 9 had become HCV-RNA negative at the end of follow-up. The absence of cirrhosis, low liver iron content, and infection with non-1b HCV type were independently associated to complete sustained response upon multivariable analysis. In conclusion, alpha-interferon may induce a sustained virologic and biochemical remission of hepatitis in beta-thalassemic patients with chronic HCV infection and nonadvanced liver disease.

Adolescent↗

Simulated car crashes and crash predictors in drivers with Alzheimer disease.

BACKGROUND: Alzheimer disease (AD) is the most common cause of dementia and can impair cognitive abilities crucial to the task of driving. Rational decisions about whether such impaired individuals should continue to drive require objective assessments of driver performance. OBJECTIVE: To measure relevant performance factors using high-fidelity driving simulation. DESIGN: We examined the effect of AD on driver collision avoidance using the Iowa Driving Simulator, which provided a high-fidelity, closely controlled environment in which to observe serious errors by at-risk drivers. We determined how such unsafe events are predicted by visual and cognitive factors sensitive to decline in aging and AD. SETTING: The University of Iowa Hospitals and Clinics, Iowa City, and the Iowa Driving Simulator. PARTICIPANTS: Thirty-nine licensed drivers: 21 with AD and 18 controls without dementia. MAIN OUTCOME MEASURES: We determined the number of crashes and related performance errors and analyzed how these occurrences were predicted by visual and cognitive factors. RESULTS: Six participants (29%) with AD experienced crashes vs 0 of 18 control participants (P = .022). Drivers with AD were more than twice as likely to experience close calls (P = .042). Plots of critical control factors in the moments preceding a crash revealed patterns of driver in-attention and error. Strong predictors of crashes included visuospatial impairment, reduction in the useful field of view, and reduced perception of 3-dimensional structure-from-motion. CONCLUSIONS: High-fidelity driving simulation provides a unique new source of performance parameters to standardize the assessment of driver fitness. Detailed observations of crashes and other safety errors provide unbiased evidence to aid in the difficult clinical decision of whether older or medically impaired individuals should continue to drive. The findings are complementary to evidence currently being gathered using techniques from epidemiology and cognitive neuroscience.

Accidents, Traffic↗

Long-duration response to levodopa influences the pharmacodynamics of short-duration response in Parkinson's disease.

The long-duration response (LDR) to chronic levodopa treatment may mask the short-duration response (SDR) to a single dose of the drug in Parkinson's disease (PD). As a result, the measurement of SDR may be inaccurate for establishing levodopa dosing regimen in individual patients. To evaluate the possible contamination of SDR by LDR, we investigated in 16 patients with PD the characteristics of SDR to a single dose of levodopa administered after a prolonged washout from chronic therapy and after a 15-day treatment period with levodopa. Levodopa treatment produced a sustained LDR, and the SDR, measured on the 15th day of treatment, had lower magnitude and shorter duration than the response recorded after washout. Moreover, after treatment, SDR did not vary between patients with mild and severe PD, whereas, after washout, severely affected patients had larger but shorter SDR than mildly affected patients. The evaluation of SDR without the interference of LDR is critical in defining the characteristics of the therapeutic response to levodopa.

Administration, Oral↗

Amiloride-inhibitable Na+ conductance in rat proximal tubule.

Previous single-channel recordings from the luminal membrane of the rabbit proximal tubule have revealed amiloride-inhibitable Na+ channels of a characteristic conductance range. The present study aimed to pursue this issue in rat proximal tubule. Control rats were compared to those put on a low-Na+ diet or pretreated by triamcinolone injections (s.c.). Stimulation of Na+ absorption by glucocorticoids was verified by examining the transepithelial voltage in Ussing chamber studies of the distal colon. The membrane voltage (Vm) of isolated, in-vitro-perfused proximal tubule segments was measured in patch-clamp and impalement studies. It was found that amiloride hyperpolarized Mv significantly by 2.1 +/- 0.9 mV (n = 26) in tubules of control rats, by 3.9 +/- 0.7 mV (n = 12) in rats put on a low-Na+ diet and by 3.7 +/- 1.0 mV (n = 17) in rats treated with glucocorticoids. The effect of amiloride was concentration dependent with a half-maximal effect at < 1 micromol/l. RT-PCR techniques were used to search for the presence of the alpha-, beta- and gamma-subunits of the epithelial Na+ channel in isolated proximal tubule segments. The presence of the respective mRNAs was verified. These data indicate that: (1) amiloride-inhibitable Na+ channels are present in rate proximal tubules; (2) the Na+ conductance may be up-regulated by Na+ deprivation but is still very limited when compared to total cell conductance; (3) therefore, the contribution of Na+-channel-mediated absorption to total proximal Na+ absorption is probably small.

Amiloride↗

Reaching with cerebral tunnel vision.

We studied reaching movements in a 48-year-old man with bilateral lesions of the calcarine cortex which spared the foveal representation and caused severe tunnel vision. Three-dimensional (3D) reconstruction of brain MR images showed no evidence of damage beyond area 18. The patient could not see his hand during reaching movements, providing a unique opportunity to test the role of peripheral visual cues in limb control. Optoelectronic recordings of upper limb movements showed normal hand paths and trajectories to fixated extrinsic targets. There was no slowing, tremor, or ataxia. Self-bound movements were also preserved. Analyses of limb orientation at the endpoints of reaches showed that the patient could transform an extrinsic target's visual coordinates to an appropriate upper limb configuration for target acquisition. There was no disadvantage created by blocking the view of the reaching arm. Moreover, the patient could not locate targets presented in the hemianopic fields by pointing. Thus, residual nonconscious vision or 'blindsight' in the aberrant fields was not a factor in our patient's reaching performance. The findings in this study show that peripheral visual cues on the position and velocity of the moving limb are not critical to the control of goal directed reaches, at least not until the hand is close to target. Other cues such as kinesthetic feedback can suffice. It also appears that the visuomotor transformations for reaching do not take place before area 19 in humans.

Cerebrovascular Disorders↗

Dementia and driving: an attempt at consensus.

The number of older drivers in Sweden will be rapidly increasing during the next decades. A possible relationship exists between the increased relative crash risk of older drivers and the prevalence of age-related diseases such as dementia. However, a clear-cut policy for evaluating driving competence in demented persons is still lacking. In recognition of this fact, the Swedish National Road Administration invited a group of researchers to formulate a consensus on the issue of driving and dementia. This consensus document is aimed at providing primary care physicians with practical advice concerning the assessment of cognitive status in relation to driving. Suggestions are based on a review of existing research and discuss the use of general and driving-specific sources of information available to the physician. Consensus was reached on the statement that a diagnosis of moderate to severe dementia precludes driving and that certain individuals with mild dementia should be considered for a specialized assessment of their driving competence.

Aged↗