Cardiac troponin-T and diagnostic test evaluation.
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Biomedical subjects
Publications and source records attributed to I Katz.
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Cyclosporin A (CsA) administered to actively growing young rats produces a high-turnover osteopenia. We investigated and compared the effect of CsA on the bone mineral metabolism in young rats with that of older rats, which have a lower rate of bone turnover. A group of 24 young (9 weeks) and 24 older (9 months) male Sprague-Dawley rats were orally administered 15 mg/kg of CsA or placebo daily for 24 days. Rats were weighed and serum assayed serially for bone gla protein (BGP), parathyroid hormone, ionized calcium, blood urea nitrogen, creatinine, and 1,25-dihydroxyvitamin D [1,25-(OH)2D]. After sacrifice, histomorphometric analysis was performed on undecalcified proximal tibial metaphysis with double-fluorescent labeling. Serum BGP levels were significantly elevated in both young and older rats administered CsA, and 1,25-(OH)2D levels were significantly elevated in CsA-treated young rats more than in older rats. Body weight was significantly reduced in CsA-treated older rats. There were mild but significant alterations in renal function in both groups receiving CsA. In the most comprehensive examination to date of the effects of CsA on bone histomorphometry, both young (-44%) and older rats (-20%) lost significant amounts of trabecular bone compared to their respective controls. Bone loss in young rats was mainly due to a reduced number of trabecular; older rats lost mainly trabecular thickness. Microanatomic nodal studies were consistent with these results. These data demonstrate that although cancellous bone loss induced by CsA is more marked in young rats, older rats with slower bone turnover are also at risk.
The effect of growth hormone (GH) treatment on body composition, resting energy expenditure (REE), and the thermic effect of food (TEF) was studied in 10 prepubertal boys (aged 6.2 to 9.5 years, with subnormal spontaneous GH secretion during the first 6 months of treatment [0.2 IU/kg.dl]). Patients were studied before and at 2, 4, and 6 months after commencing treatment. Height and weight increased significantly during treatment (112.2 +/- 4.5 to 117.2 +/- 6.0 cm and 18.0 +/- 2.8 to 20.8 +/- 3.2 kg, respectively). Body fat percent decreased significantly (15.93% +/- 4.08% to 11.97% +/- 3.30%, P < .0002), but was not different at 4 and 6 months. Total body potassium (TBK) increased significantly (39.15 +/- 5.77 to 48.70 +/- 6.35 g, P < .001) during treatment. When correcting for the expected changes in body composition over time, height and weight were still shown to increase, fat percent decreased significantly, but TBK and mid-arm muscle circumference (MAMC) were not different from the expected values. REE increased significantly during treatment, but when it was expressed per TBK or corrected for the change in kilograms of fat-free body mass (FFBM), it increased only at 2 months and stabilized thereafter. The TEF was increased at 2 and 4 months of treatment and returned to pretreatment levels at 6 months of treatment. Substrate utilization as studied by indirect calorimetry pointed toward a significant protein-sparing effect during the first 4 months of treatment; this change tended to disappear in resting energy metabolism by 6 months of GH treatment.(ABSTRACT TRUNCATED AT 250 WORDS)
Treatment of 21 steroid-dependent asthmatic patients with methotrexate (MTX) 15 mg/week was prospectively evaluated for a mean of 14.7 (SD 3.7) months. Before MTX, therapy consisted of a mean prednisone dose of 16.6 (SD 9.2) mg, in addition to inhaled beclomethasone/budesonide (mean daily dose 1157 (SD 330) micrograms) and bronchodilators. Thirteen patients were weaned from all regular systemic steroid therapy, a 50% or more reduction was achieved in four patients, and a less than 50% reduction in four patients. Abnormal liver function tests were noted in six of the 21 patients; this resolved despite continuation of MTX in five. In one patient, MTX was stopped because of symptoms as well as a fivefold rise in serum transaminases, and a speedy resolution was noted. Gastrointestinal side-effects were reported in six patients but were resolved in five with intramuscular MTX. There were no hematologic or pulmonary complications. We conclude that MTX appears to be both safe and efficacious as a steroid-sparing agent in most steroid-dependent asthmatic patients when taken over a long period.
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BACKGROUND: Cholesterol and calcium are prominant components within human atherosclerotic lesions. Both accumulate predominantly within the central core region of lesions. Because of similarities in some crystallographic faces of cholesterol monohydrate and calcium apatite, it has been previously proposed that deposition of one may nucleate the deposition of the other. EXPERIMENTAL DESIGN: In this study, we have used the technique of confocal fluorescence microscopy to assess the spatial orientation of cholesterol in association with calcium mineral. Localization of cholesterol within mineral was carried out by staining cholesterol with the fluorescent probe, filipin. RESULTS: With this technique, it was possible to localize cholesterol associated with the surface of hydroxyapatite seeds, cholesterol incorporated within calcium phosphate-cholesterol agglomerates produced in vitro, and cholesterol within apatite isolated from human atherosclerotic lesions. CONCLUSIONS: The presence of cholesterol within the center of calcified granules from atherosclerotic plaque suggests that cholesterol or associated lipids may act to nucleate the deposition of apatite. Confocal fluorescence microscopy should be a useful technique by which to study the relationship of cholesterol associated with calcium minerals that occur not only in atherosclerotic blood vessels, but also in gallstones, and calcified cardiac valves.
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Immunosuppressants have adverse effects on bone mineral metabolism in animal and human studies, with corticosteroids producing low-turnover osteopenia, and cyclosporin-A (CsA) producing high-turnover osteopenia. Rapamycin (RAPA) is a new immunosuppressant reported to be at least 10 times more potent than CsA, and acts via a different pathway to CsA and the other new immunosuppressant FK506. This study investigated the effects of RAPA on bone mineral metabolism in the rat. Forty-two, 10-week-old, male Sprague Dawley rats were divided into three groups, and treated according to the following protocol: group A (control) received RAPA vehicle by daily gavage for 14 days (n = 12); group B (high dose RAPA) received RAPA 2.5 mg/kg/day by daily gavage for 14 days (n = 15); group C (low dose RAPA) received RAPA 1.25 mg/kg/day by daily gavage for 14 days (n = 15). Rats were weighed and bled on days 0, 7, and 14 for measurement of blood ionized calcium, bone Gla protein (BGP), parathyroid hormone (PTH), and 1,25(OH)2D. Tibial bone histomorphometry was determined on day 14 after double-calcein labeling. Weight gain was similar in the two groups treated with RAPA compared with control animals. High-dose RAPA (group B) transiently depressed serum BGP levels on day 7, with elevated blood ionized calcium levels on day 7, and lowered 1,25(OH)2D levels on day 14. Serum PTH levels were unchanged. Low-dose RAPA (group C) did not affect calciotropic hormones.(ABSTRACT TRUNCATED AT 250 WORDS)
OBJECTIVES: This study examined the long-term (3-month) effects of nebivolol, a new beta-adrenergic blocking agent, on cardiac performance in patients with dilated cardiomyopathy. BACKGROUND: Several beta-blocking drugs have been reported to have a beneficial hemodynamic effect in patients with dilated cardiomyopathy, but few data obtained in a placebo-controlled randomized study have addressed the mechanisms of improvement. METHODS: Twenty-four patients with dilated idiopathic (n = 22) or ischemic (n = 2) cardiomyopathy (ejection fraction 0.15 to 0.40) in stable New York Heart Association functional class II or III were entered into a double-blind randomized trial of nebivolol, a new, potent, selective beta 1-antagonist. Exercise time, invasive hemodynamic data (12- and 24-h monitoring) and variables of left ventricular function were examined at baseline and after 3 months of orally administered nebivolol (1 to 5 mg/day, n = 11) or placebo (n = 13). RESULTS: Heart rate decreased (group mean 85 to 71 beats/min vs. 87 to 87 beats/min with placebo) and stroke volume increased significantly (group mean 43 to 55 ml vs. 42 to 43 ml) with nebivolol; decreases in systemic resistance, systemic arterial pressure, wedge pressure and pulmonary artery pressure were not significantly different from those with placebo. Similar hemodynamic results were obtained in the catheterization laboratory. Analysis of high fidelity measurements of left ventricular pressure showed a decrease in left ventricular end-diastolic pressure in the nebivolol group (group mean 21 to 15 vs. 24 to 20 mm Hg with placebo) but no change in the maximal rate of pressure development or in two variables of left ventricular relaxation (maximal negative rate of change of left ventricular pressure [dP/dtmax] and the time constant tau). Left ventricular mass decreased (p = 0.04). Despite a decrease in heart rate with nebivolol, there was a slight decrease in left ventricular end-diastolic volume (p = NS). End-systolic volume tended to decrease (p = 0.07) despite no reduction in end-systolic stress. The net result was a significant increase in ejection fraction (group mean 0.23 to 0.33 vs. 0.21 to 0.23 with placebo), presumably as a result of an increase in contractile performance. This effect was corroborated by an increase in a relatively load-independent variable of myocardial performance. CONCLUSIONS: Nebivolol improved stroke volume, ejection fraction and left ventricular end-diastolic pressure, not through a measurable reduction in afterload or a lusitropic effect, but by improving systolic contractile performance.
BACKGROUND: Sighing breathing is observed in subjects suffering from anxiety with no apparent organic disease. METHODS: Lung volumes and expiratory flow rates were measured in 12 patients with a sighing pattern of breathing and in 10 normal subjects matched for age, gender, and anthropometric data. In both groups the measurements were made by spirographic and plethysmographic techniques. In normal subjects functional residual capacity (FRC) and residual volume (RV) were measured during normal breathing and again during simulated sighing breathing to exclude technical artifacts resulting from hyperventilation during measurement by the helium closed circuit method. RESULTS: Patients with a sighing pattern of breathing had a normal total lung capacity (TLC) but significantly different partitioning of lung compartments compared with normal subjects. The vital capacity (VC) was lower when measured by both spirographic and plethysmographic methods and RV was higher. The forced expiratory volume in one second (FEV1) was also lower in patients with sighing breathing. The FEV1/VC and the maximal expiratory flow rates at 50% and at 25% of the forced vital capacity (V50 and V25) were normal and similar in both groups. In normal subjects there were no differences in RV when measured during quiet or simulated sighing breathing. CONCLUSIONS: Subjects with sighing breathing have a normal TLC with a higher RV and lower VC than normal subjects. There was no obvious physiological or anatomical explanation for this pattern.
Different aspects of mechanical loading were analyzed in a group of 25 patients with chronic obstructive pulmonary disease (COPD) who all had severe expiratory airflow limitation but different arterial CO2 values. It was found that the maximal expiratory flow rates (V75, V50, V25, VFRC), functional residual capacity (FRC), residual volume (RV), total lung capacity (TLC), specific airways conductance (SGaw) measured during inspiration or expiration, and lung recoil pressure (PLel) were not correlated to the PaCO2. Only five parameters were significantly linked to the PaCO2; they were the peak inspiratory flow (PIF) (r = -0.57, p < 0.002), the inspiratory vital capacity (IVC) (r = -0.46, p < 0.01), the maximal voluntary ventilation (MVV) (r = -0.49, p < 0.01), the total SGaw (r = -0.40, p < 0.03), and the forced expiratory flow volume in one second (FEV1) (r = -0.36, p < 0.05). It was concluded that the airflow limitation during the inspiratory phase has an important contribution to the CO2 retention in patients with COPD, and therefore analysis of both phases of the respiratory cycle is necessary to assess the severity of airway obstruction in this disease.
The large number of drugs available to treat schizophrenia and the emergence of atypical and newer agents that provide efficiency with lessening of side effects may not only serve to provide more amelioration against this disease, but may also help us to unravel the neurochemical defects of the disorder. Despite these encouraging trends, the reality is that schizophrenia is still a devastating illness for a sizeable minority affected with the condition, that a 'cure' is not yet possible, and that drug therapies alone will not provide all that is required in acute or continuing management. Supporting care in the community for patient and family are just as important as pharmacotherapy in managing this problem.
BACKGROUND: Malignant melanomas (MMs) with a small diameter (less than 6 mm) are rarely removed surgically; therefore there is a need for more data to characterize them. OBJECTIVE: The purpose of this study was to further elucidate the clinical and histopathologic features of small melanomas. METHODS: The greatest diameters of 112 consecutively submitted MMs were measured histologically. Those lesions with diameters of less than 6 mm were further studied clinically and histopathologically. RESULTS: Four MMs (3.5%) were found to have small histologic diameters. Their clinical features differed from the classic clinical ABCD's, although their histopathologic features resembled those of large MMs. Their depth of dermal invasion was relatively superficial, and their clinical outcome was favorable. CONCLUSION: Histopathologically, small MMs tend to resemble large MMs, but clinically they may require other diagnostic criteria. Because they tend to show a relatively superficial depth of invasion, their increased recognition and removal may have an impact on overall mortality from MM.
We have presented an immunocompetent patient who, after paternal lymphocyte immunization, developed a GVH-like skin reaction; she recovered spontaneously. This complication is rarely seen. This was the only case observed in our series of over 70 patients immunized. A similar phenomenon was not reported in a larger series by Carp and colleagues (1). However, the case deserves special attention because this reaction can be life-threatening. Therefore, we suggest that paternal lymphocyte immunization should be recommended only for those patients who have undergone a thorough work-up and in whom all causes, other than immunological, for recurrent abortion have been excluded. Even then, this treatment should be given with utmost caution. In view of the above described complication, we believe that more data are still required to justify offering such a treatment modality on a routine basis.
Analytical estimates of the respirable fractions on inhaled pharmaceutical aerosols are obtained by inertial sampling techniques. The respirable fraction may be defined as that portion of the particle size distribution less than a designated diameter. The diameter size below which particles were considered respirable in these studies was 6.4 microns. In clinical practice, a variety of particle size distributions may be related to a single respirable fraction. Herein, three respirable fractions were each defined by six particle size distributions. The deposition patterns of aerosols exhibiting these particle size characteristics were examined in a mathematical model. The analytically defined respirable fractions were compared with predicted lung deposition values. Under clearly defined breathing conditions, there is a correlation between the nominal respirable fraction and deposition. However, it was concluded that the variations which occur in breathing parameters within patient populations may not allow a single analytically derived respirable fraction to be appropriate for all individual subjects.
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Cyclosporin-A (CsA) administered to the oophorectomized rat exaggerates the high turnover osteopenia associated with oophorectomy alone. This study investigated whether 17 beta-estradiol replacement could influence the development of osteopenia in the oophorectomized rat treated with CsA. Ninety female Sprague-Dawley rats, approximately 300 g in weight, were divided into 6 groups of 15 each and treated according to the following protocol: group A were sham operated (control), group B underwent oophorectomy (Ox), group C underwent Ox and received CsA (15 mg/kg, by daily gavage) for 28 days (Ox and CsA), group D underwent Ox and received CsA and a 0.1 mg 17 beta-estradiol pellet (EP) implanted sc (Ox, CsA, and EP), group E underwent Ox and received EP (Ox and EP), and group F, which was intact and nonoperated, received CsA (CsA). Rats were weighed and bled on days -7, 0, 7, 14, 21, and 28 for measurement of blood ionized calcium, bone Gla protein (BGP), 17 beta-estradiol, and PTH. Bone histomorphometry was determined after double tetracycline labeling. On day 28, serum 17 beta-estradiol was undetectable in groups B (Ox) and C (Ox and CsA), and similar to group A (control) in groups D (Ox, CsA, and EP), E (Ox and EP), and F (CsA). Oophorectomy resulted in a significant gain in weight in groups B (Ox) and C (Ox and CsA), which was prevented by 17 beta-estradiol in groups D (Ox, CsA, and EP) and E (Ox and EP). On day 28, serum BGP levels were higher in groups B (Ox; 73.58 +/- 3.63 ng/ml), C (Ox and CsA; 85.05 +/- 9.88), and F (CsA; 81.35 +/- 3.4) compared to group A (control; 46.07 +/- 5.52; P less than 0.05), while 17 beta-estradiol in groups D (Ox, CsA, and EP; 38.65 +/- 2.85) and E (Ox and EP; 41.89 +/- 1.89) prevented this rise (P = 0.01). BGP levels in group C (Ox and CsA) were higher on days 14 and 21 compared to group B (Ox). Groups D (Ox, CsA, and EP) and E (Ox and EP) had elevated blood ionized calcium levels from day 7 onward. Serum PTH levels were unchanged. Histomorphometric analyses of tibial metaphyses revealed increased parameters of bone formation and resorption, with significant loss of bone volume, in groups B (Ox; 12.03 +/- 1.40%) and C (Ox and CsA; 11.43 +/- 2.20) vs. group A (control; 24.36 +/- 2.37; P less than 0.05).(ABSTRACT TRUNCATED AT 400 WORDS)
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