The "magic angle" effect: background physics and clinical relevance.
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Cartilage↗
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Diaphragmatic motion: fast gradient-recalled-echo MR imaging in healthy subjects.
PURPOSE: To investigate the feasibility of imaging diaphragmatic motion with a fast gradient-recalled-echo (GRE) magnetic resonance (MR) pulse sequence. MATERIALS AND METHODS: Fast GRE pulse sequences in sagittal and coronal planes were used to acquire repeated, single-level, 1.2-second scans in 10 healthy volunteers during deliberately slowed, approximate-vital-capacity breathing. Motion was analyzed subjectively by viewing the image sequences as cine loops and quantitatively by measuring the displacement of different points on the diaphragm at a workstation. RESULTS: Temporal and spatial resolutions were adequate in all subjects. Absolute excursion of the domes was 4.4 cm on the right and 4.2 cm on the left. Analysis of diaphragmatic displacement at different locations revealed a gradient of excursion that increased from anterior to middle to posterior (P < .05-.001; paired t test). Excursion of the lateral aspects was greater than that of the medial aspect (P < .001). CONCLUSION: Fast GRE MR imaging can be reliably used to demonstrate diaphragmatic motion and may prove useful in the investigation of normal and abnormal respiratory mechanics.
Adult↗
Hyaline cartilage: truncation artifact as a cause of trilaminar appearance with fat-suppressed three-dimensional spoiled gradient-recalled sequences.
PURPOSE: To investigate the cause of the trilaminar appearance within hyaline cartilage observed on magnetic resonance (MR) images obtained with a fat-suppressed three-dimensional spoiled gradient-recalled sequence. MATERIALS AND METHODS: The knees of three asymptomatic volunteers were imaged with a fat-suppressed, three-dimensional, spoiled gradient-recalled sequence. The field of view, number of phase-encoding steps, and phase-encoding direction were varied. On each image, the thickness of the patellar and trochlear cartilage was measured in millimeters and divided by the pixel dimension, which effectively expressed the thickness as the number of pixels. Finally, the number of pixels was compared with the number of alternating hyperintense and hypointense lines depicted. RESULTS: The number of truncation lines increased as pixel dimension was reduced by either decreasing the field of view or increasing the number of phase-encoding steps. The accuracy for predicting more than three lines with use of an anteroposterior phase-encoding direction varied between 83% and 92%. The appearance of the cartilage was altered when phase- and frequency-encoding directions were exchanged, but truncation lines were still evident. CONCLUSION: The trilaminar appearance depicted within hyaline cartilage on MR images obtained with this sequence is predominantly attributable to truncation artifact rather than to histologic zonal anatomy.
Adult↗
Brain tumors: localized H-1 MR spectroscopy at 0.5 T.
PURPOSE: To investigate the feasibility of obtaining clinically useful magnetic resonance (MR) spectra at 0.5 T in cerebral lesions. MATERIALS AND METHODS: Single-voxel localized proton MR spectroscopy was performed at 0.5 T in 18 patients (aged 16-73 years) suspected of having cerebral lesions on MR images who subsequently underwent craniotomy and biopsy and in eight volunteers (aged 21-50 years). The metabolite resonances in the MR spectra were stratified according to the histologic diagnosis. MR spectra demonstrated resonances for choline-containing compounds (Cho), creatine and phosphocreatine, glutamine and glutamate, N-acetylaspartate (NAA), myo-inositol, and lactate. RESULTS: In 14 of 15 patients with cerebral tumors, the Cho-NAA ratio was increased and was greater than 1. In three patients with nonneoplastic cerebral lesions, the ratio did not exceed 1. In healthy control subjects, the average ratio was 0.54. CONCLUSION: H-1 MR spectroscopy at 0.5 T provides clinically useful information in patients with cerebral lesions.
Adolescent↗
Focal brain lesions: effect of single-voxel proton MR spectroscopic findings on treatment decisions.
PURPOSE: To determine the influence of single-voxel proton magnetic resonance (MR) spectroscopic findings on the treatment of patients suspected of having a brain tumor. MATERIALS AND METHODS: Medical records were reviewed in 78 patients who underwent MR spectroscopy for evaluation of a focal brain mass suspected of being neoplastic. MR spectroscopic findings were positive for neoplasm in 49 patients and negative in 29. Treatment with or without performance of biopsy was noted. In patients with positive findings who underwent irradiation or chemotherapy without biopsy and in patients with negative findings who were treated medically or followed up for interval changes, MR spectroscopy was classified as having a potential positive influence on treatment. In patients with positive findings with subsequently proved nonneoplastic lesions and in patients with negative findings with subsequently proved tumors, MR spectroscopy was classified as having a potential negative influence. RESULTS: MR spectroscopy in eight (16%) patients with positive findings and in 15 (52%) patients with negative findings had a potential positive influence on treatment. In two (3%) patients, MR spectroscopy had a potential negative influence. CONCLUSION: MR spectroscopy may play a beneficial role in the management of suspected brain tumors. Prospective studies are needed to test the effect of MR spectroscopy on clinical practice and to measure costs and benefits.
Adolescent↗
Echocardiographic evaluation of ventricles during continuous positive airway pressure breathing.
Using M-mode and two-dimensional echocardiography, we have compared left and right ventricular dimensions at expiration and inspiration in a group of 12 healthy young volunteers during the following two distinct periods: 1) a control period with atmospheric pressure breathing, and 2) a continuous positive airway pressure (CPAP) period with 15 cmH2O end-expiratory pressure breathing. In 6 of the 12 subjects we also evaluated inferior vena caval size, using the same technique. Inspiratory decrease in left ventricular short-axis area (A), length (L), calculated volumes (V = 5/6 AL), and inspiratory increase in right ventricular short-axis diameter and long-axis area were evident at both control and CPAP periods. CPAP also produced a marked decrease in left and an increase in right ventricular dimensions during both expiration and inspiration and a significant decrease in calculated stroke output. An increase in vena caval size during CPAP breathing indirectly suggested a decrease in venous return, but the finding of an unchanged percent of inspiratory change of this vessel during CPAP indicated that the inspiratory augmentation of venous return was still present. On the other hand, the finding of an increased right ventricular size indicated that the right ventricle was afterloaded by CPAP; this probably could explain the observed reduction in calculated stroke output.
Adult↗
Inflammatory, hemostatic, and clinical changes in a baboon experimental model for heatstroke.
The mortality and neurological morbidity in heatstroke have been attributed to the host's inflammatory and hemostatic responses to heat stress, suggesting that immunomodulation may improve outcome. We postulated that an experimental baboon model of heatstroke will reproduce human responses and clinical outcome to allow testing of new therapeutic strategies. Eight anesthetized juvenile baboons (Papio hamadryas) were subjected to heat stress in an incubator maintained at 44-47 degrees C until rectal temperature attained 42.5 degrees C (moderate heatstroke; n = 4) or systolic arterial pressure fell to <90 mmHg (severe heatstroke; n = 4) and were allowed to recover at room temperature. Four sham-heated animals served as a control group. Rectal temperature at the end of heat stress was 42.5 +/- 0.0 and 43.3 +/- 0.1 degrees C, respectively. All heat-stressed animals had systemic inflammation and activated coagulation, indicated by increased plasma IL-6, prothrombin time, activated partial thromboplastin time, and D-dimer levels, and decreased platelet count. Biochemical markers and/or histology evidenced cellular injury/dysfunction: plasma levels of thrombomodulin, creatinine, creatine kinase, lactic dehydrogenase, and alanine aminotransferase were increased, and varying degrees of tissue damage were present in liver, brain, and gut. No baboon with severe heatstroke survived. Neurological morbidity but no mortality was observed in baboons with moderate heatstroke. Nonsurvivors displayed significantly greater coagulopathy, inflammatory activity, and tissue injury than survivors. Sham-heated animals had an uneventful course. Heat stress elicited distinct patterns of inflammatory and hemostatic responses associated with outcome. The baboon model of heatstroke appears suitable for testing whether immunomodulation of the host's responses can improve outcome.
Animals↗
Evaluation of two-way protein fluxes across the alveolo-capillary membrane by scintigraphy in rats: effect of lung inflation.
Pulmonary microvascular and alveolar epithelial permeability were evaluated in vivo by scintigraphic imaging during lung distension. A zone of alveolar flooding was made by instilling a solution containing 99mTc-albumin in a bronchus. Alveolar epithelial permeability was estimated from the rate at which this tracer left the lungs. Microvascular permeability was simultaneously estimated measuring the accumulation of (111)In-transferrin in lungs. Four levels of lung distension (corresponding to 15, 20, 25, and 30 cmH2O end-inspiratory airway pressure) were studied during mechanical ventilation. Computed tomography scans showed that the zone of alveolar flooding underwent the same distension as the contralateral lung during inflation with gas. Increasing lung tissue stretch by ventilation at high airway pressure immediately increased microvascular, but also alveolar epithelial, permeability to proteins. The same end-inspiratory pressure threshold (between 20 and 25 cmH2O) was observed for epithelial and endothelial permeability changes, which corresponded to a tidal volume between 13.7 +/- 4.69 and 22.2 +/- 2.12 ml/kg body wt. Whereas protein flux from plasma to alveolar space ((111)In-transferrin lung-to-heart ratio slope) was constant over 120 min, the rate at which 99mTc-albumin left air spaces decreased with time. This pattern can be explained by changes in alveolar permeability with time or by a compartment model including an intermediate interstitial space.
Animals↗
Impaired serum lipids and lipoproteins in fetal macrosomia related to maternal obesity.
The aim of this work was to determine lipoprotein metabolism alterations in macrosomic newborns and to see whether these lipoprotein abnormalities are parallel or not to those found in their obese or nonobese mothers. Serum lipids, apo A-I, apo B100, lipoproteins (VLDL, LDL, HDL2, and HDL3), and LCAT activity were investigated in obese and nonobese mothers and cord blood of their macrosomic or appropriate-for-gestational-age (AGA) newborns. Serum and VLDL triglyceride concentrations were higher in obese mothers of AGA newborns than in nonobese mothers. Serum triglyceride, VLDL, and apo B100 levels were higher, while serum apo A-I and HDL2 cholesterol concentrations were lower in obese mothers of macrosomic newborns than in the other groups. In their macrosomic newborns, serum lipid, lipoprotein, apo B100, and apo A-I levels were higher as compared with those of other newborns. Macrosomic newborns of nonobese mothers had lipoprotein profiles similar to those in AGA newborns. LCAT activity was similar in both mother groups and in both newborn groups. In conclusion, maternal obesity and fetal macrosomia were associated with lipoprotein abnormalities consistent with high atherogenic risk.
Adult↗
The use of itraconazole to treat cutaneous fungal infections in children.
BACKGROUND: Cutaneous mycoses such as tinea capitis, onychomycosis and some cases of tinea corporis/cruris, and tinea pedis/manus require oral antifungal therapy. There is relatively limited data regarding the use of the newer oral antifungal agents, e.g. itraconazole, in the treatment of these mycoses in children. OBJECTIVE: We wished to determine the efficacy and safety of itraconazole continuous therapy in the management of cutaneous fungal infections in children. METHODS: Children with cutaneous mycoses were treated with itraconazole in an open-label manner in 4 studies. For tinea capitis, the treatment regimens using itraconazole continuous therapy were: study 1, 3 mg/kg/day for 4 or 8 weeks; study 2, 5 mg/kg/day for 6 weeks, and study 3, 5 mg/kg/ day for 4 weeks. In a different trial, study 4, itraconazole continuous therapy 5 mg/kg/day was used to treat toenail onychomycosis (duration: 12 weeks), tinea corporis/ cruris (duration: 1 week) and tinea pedis/manus (duration: 2 weeks). RESULTS: The efficacy rates at follow-up 12 weeks from the start of therapy in children with tinea capitis treated using the itraconazole continuous regimen were: clinical cure (CC) and mycological cure (MC) in study 1 (n = 10, Trichophyton violaceum all patients), CC 50%, MC 86%; in study 2 (n = 35, Microsporum canis 22 patients, Trichophyton sp. 12 patients), CC 82.8%, MC 80%, and in study 3 (n = 16, M. canis 11 patients, Trichophyton sp. 5 patients), (CC 66.7%, MC 78.5%. Itraconazole was also effective in the treatment of dermatomycoses in 24 children (study 4). The CC and MC rates at the follow-up 8 weeks from the start of therapy in children with dermatomycoses and 12 months in children treated for onychomycosis were: onychomycosis (n = 1, T. rubrum), CC 100%, MC 100%; tinea corporis (n = 12, M. canis 10 patients), CC 100%, MC 90%; tinea cruris (n = 3, Trichophyton sp. 2 patients), CC 100%, MC 100%; tinea manus (n = 1, T. rubrum), CC 100%, MC 100%, and tinea pedis (n = 7, T. rubrum), CC 100%, MC 100%). Adverse effects consisted of a cutaneous eruption in 1 (1.2%) of the 85 children, with mild, transient, asymptomatic elevation of liver function tests (less than twice the upper limit of normal) in 2 (3.4%) of 58 children in whom monitoring was performed. CONCLUSIONS: Itraconazole is effective and safe in the treatment of tinea capitis and other cutaneous fungal infections in children.
Antifungal Agents↗
IGHV3-associated restriction fragment length polymorphisms confer susceptibility to bullous pemphigoid.
OBJECTIVE: To determine whether the immunoglobulin heavy chain genes contribute to the occurrence of bullous pemphigoid (BP), polymorphisms of both the immunoglobulin constant IGHC and variable IGHV groups were studied in 100 Caucasian BP patients and 143 ethnically matched healthy individuals. METHODS: To analyze the restriction fragment length polymorphism (RFLP) of the IGHG constant locus, a genomic immunoglobulin gamma 3 probe which detects polymorphisms in the gamma constant genes was hybridized to BstEII- or BamHI/SacI-digested germline DNA, while IGHV3 subgroup polymorphism was analyzed by hybridizing a cloned VH3 probe to EcoRI-digested DNA. RESULTS: No difference in the frequencies of the genotypes defined by the constant probe was observed between patients and controls. Analysis of the RFLP obtained with the VH3 probe showed that within the range of 4.5 and 1.5 kb, the observed band pattern was composed of 8 monomorphic and 7 polymorphic bands. Among the latter, 4 allowed to define 10 different restriction patterns. One pattern was shown to be significantly less frequent in patients than in controls. CONCLUSION: IGHV3 polymorphism might be a factor conferring susceptibility to BP.
Deoxyribonucleases, Type II Site-Specific↗
Chronic pemphigoid gestationis: comparative clinical and immunopathological study of 10 patients.
BACKGROUND: Pemphigoid gestationis (PG) is a rare autoimmune bullous disorder occurring during the last trimester of pregnancy and usually regressive within 3 months after delivery. Prolonged forms of the disease lasting more than 6 months after delivery have been reported as chronic PG. OBJECTIVE: The aim of the present study was to compare the clinical and immunopathological findings between 4 patients presenting a normal regression of the disease after delivery and 6 patients with a chronic course. METHODS: All patients were evaluated and studied by clinical patterns (age, mucosal and cutaneous involvement, obstetrical history, duration of the blistering disease and response to treatment), by direct and indirect immunofluorescence and Western blot. Eight patients were studied by immunoelectron microscopy (IEM) and 3 patients had an indirect IEM. RESULTS: Patients with chronic PG were older, had multigravidity, a history of PG during previous pregnancies, widespread cutaneous eruption and mucosal involvement. Subclass analysis of circulating autoantibodies showed an IgG1 anti-BP180 response in all patients except 1 with disease of 7 years' duration. Direct IEM was positive in 6/8 patients showing a labeling of the lamina lucida, and indirect IEM using colloidal gold probes confirmed the localization of the target antigens to the proximal part of the anchoring filaments in the lamina lucida. CONCLUSION: This study suggests that, even in chronic long-lasting PG, IgG1 remains the predominant subtype of IgG. Therefore no biological and predictable marker of chronicity can be ascertained from this series.
Adult↗
Clinical criteria for the diagnosis of bullous pemphigoid: a reevaluation according to immunoblot analysis of patient sera.
BACKGROUND: We previously proposed a set of 4 clinical criteria for the diagnosis of bullous pemphigoid (BP) that consisted of age greater than 70 years, absence of atrophic scars, absence of mucosal involvement and absence of predominant bullous lesions on the neck and head. These results have been challenged because direct immunoelectron microscopy (IEM), which was used as the standard diagnostic criterion in our initial study, does not identify the different antigens of the basement membrane zone. OBJECTIVE: To reassess the validity of these clinical criteria for the diagnosis of BP using immunoblot analysis of patient sera as the main diagnostic criterion, in order to precisely identify the antigens recognized by patient sera. METHODS: One hundred and eighty-nine sera from patients with various subepidermal autoimmune blistering diseases (AIBDs) were tested by immunoblotting using dermal and epidermal extracts. IEM was used as a complementary diagnostic procedure in a few patients whose serum recognized BPAG2 exclusively or was negative in immunoblotting. RESULTS: 142 patients (75%) had at least 3 of the 4 clinical diagnostic criteria. Sera from patients who lacked the set of BP clinical criteria were more frequently immunoblot negative (34%) than sera from patients who had the criteria (18%; p = 0.025). BPAG1 was more frequently recognized by sera from patients with the set of BP clinical criteria (78%) than by sera from patients without the criteria (45%; p = 5.10(-4)). In contrast, BPAG2 was recognized by a great number of sera from patients who lacked the criteria of BP (71%), which was in accordance with the presence of numerous patients with cicatricial pemphigoid in this group. Among patients with various subepidermal AIBDs, the diagnosis of BP could be made with a sensitivity of 86%, a specificity of 90% and an excellent prognostic positive value over 95%, if 3 of these clinical criteria were present. CONCLUSION: These results confirm the interest of this set of clinical criteria for the rapid diagnosis of BP.
Aged↗
Consensus statement on the safety profile of topical calcineurin inhibitors.
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Administration, Topical↗
The differential diagnosis of red eye: a survey of medical practitioners from Eastern Europe and the Middle East.
A survey amongst ophthalmologists and general medical practitioners from nine countries in Eastern Europe and the Middle East was conducted to estimate the percentage of patients presenting with a red eye and to examine differential diagnosis and treatment. Practitioners recorded brief details of every patient seen and detailed information concerning signs and symptoms, differential diagnosis and treatment for all patients presenting with a red eye during 20 consecutive days in the period between May and September 2004. Red eyes accounted for approximately 15% of consultations with ophthalmologists and almost 6% with general medical practitioners. Allergic conjunctivitis was the most common diagnosis (35%), followed by dry eye (25%) and bacterial conjunctivitis (24%). General medical practitioners were far more likely to prescribe a combination topical antibiotic and steroid preparation than ophthalmologists. This survey illustrates that red eye remains a very important problem for both ophthalmologists and general medical practitioners. Identification of dry eye as a common cause of red eye symptoms and more appropriate treatment of dry eye, allergic conjunctivitis and viral conjunctivitis are key messages to emerge.
Adolescent↗
Renal hemodynamic effects of tertatolol compared with those of propranolol in the conscious dog.
Experiments were performed in which the effects of two beta-blockers, tertatolol [dl-(hydroxy-2'-t-butyl-amino-3'-propyloxy)-8-thiochroman hydrochloride] and propranolol, on mean arterial pressure (MAP), heart rate (HR), and renal function were studied in the conscious sodium-replete dog. In all experiments renal function was evaluated from the effective renal plasma flow (ERPF) and glomerular filtration rate (GFR) assessed respectively by measurement of p-aminohippurate and creatinine clearances. These parameters were measured during two 30-min control periods, after which two further measurements were performed over a similar time period, after intravenous administration of either propranolol (0.5 mg X kg-1; n = 8) or tertatolol (0.05 mg X kg-1; n = 8), these two doses being of equivalent beta-adrenoceptor antagonist activity. Administration of propranolol and tertatolol did not change MAP but induced a significant and comparable decrease in HR. After propranolol a significant decrease in ERPF was observed, without any change in GFR or sodium excretion. In contrast, administration of tertatolol resulted in no modification of ERPF, a slight but significant increase in GFR, and a significant increase in sodium and potassium excretion. These results suggest that tertatolol and propranolol though acting similarly on systemic parameters have different effects on renal hemodynamics in the conscious dog.
Adrenergic beta-Antagonists↗
Tertatolol preserves renal perfusion in patients with arterial hypertension after head injury.
Tertatolol is a noncardioselective beta-adrenergic blocking agent without partial agonist activity. Its central and renal hemodynamic effects were compared to those of an equipotent dosage of propranolol in two groups of 10 patients each who developed arterial hypertension and a hyperdynamic circulatory state after head injury. After tertatolol, 5 mg orally, mean arterial blood pressure was unaffected, heart rate decreased by 22% (p less than 0.01) and cardiac index by 24% (p less than 0.01) while renal blood flow remained unchanged (-5%; not significant) so that the renal fraction of cardiac index was increased by 22% (p less than 0.05). After propranolol, 160 mg orally, mean arterial blood pressure was not modified, heart rate decreased by 12% (p less than 0.01), cardiac index by 16% (p less than 0.01) and renal blood flow by 17% (p less than 0.01) so that the renal fraction of cardiac index remained unchanged (-3%; not significant). Tertatolol is a potent beta-blocking agent comparable to propranolol apart from the fact that it preserves renal perfusion; this peculiar effect is related to a redistribution of the reduced cardiac output to the benefit of the kidney.
Adolescent↗
Choosing the right dose for beta-blocker treatment of hypertension: experience with tertatolol.
The determination of the optimum dosage for antihypertensive therapy, i.e. the unit dose and the administration frequency, remains one of the least discussed subjects. For beta-blockers as well as for other drugs, this determination is mainly based on the dose-effectiveness curve, the top of which corresponds to the right dose. Thus, a wide range of doses should be tested, and this as early as possible during drug development. The first step is to assess the optimum beta-blocking dose in healthy volunteers during phase I studies. These dose-response studies are usually performed according to a cross-over design. Among the many techniques proposed for assessing the effects of beta-blockers in man, isoprenaline and dynamic exercise tests are the most commonly used. The second step is to make use of the previous results to find the right dose for hypertensive patients in phase II studies. However, many individual factors which can influence the blood pressure response should be kept in mind, especially the initial blood pressure level. The choice of the design is generally based on the need to have repeated administration in order to obtain optimum control of the hypertension. Therefore, the cross-over design, although theoretically the best one, is rarely used on account of its practical and ethical problems. In contrast, the parallel design, with random assignment of treatments, is suitable to most experimental situations. Very different in nature, the stepped dose design stems from an ethical and practical approach of dose finding and thus is also widely used. Finally, correct measurement techniques of blood pressure are required.(ABSTRACT TRUNCATED AT 250 WORDS)
Adrenergic beta-Antagonists↗