Calciphylaxis in uraemic and nonuraemic settings: clinical risk factors and histopathological findings.

BACKGROUND: Calciphylaxis is a life-threatening cutaneous ulcerative/necrotic disease characterized by vascular calcification/occlusion. It occurs most commonly in end-stage kidney disease (ESKD), known as uraemic calciphylaxis (UC) but can also occur in patients with chronic kidney disease (CKD) and normal kidney function (nonuraemic calciphylaxis; NUC). There are few large series of NUC in the literature. AIM: To compare the clinicopathological features of UC and NUC. METHODS: We retrospectively compared the clinicopathological features of 35 patients with NUC during the period 2010-2020 with those of 53 patients with UC (control group). Cases were classified as NUC in the absence of all of the following: ESKD, significant CKD (defined as serum creatinine > 3 mg/dL or creatinine clearance < 15 mL/min) and acute kidney injury requiring kidney replacement therapy or kidney transplantation. RESULTS: NUC represented 40% of the total cases, and there was a higher number of women (P < 0.01) and a higher median body mass index (P = 0.06) compared with the control UC group. Elevated parathyroid hormone was present in 44% of patients with NUC. Most of the tested patients were positive for lupus anticoagulants (56%). NUC biopsies showed a higher rate of extravascular calcium deposits (73% vs. 47%, P = 0.03). Dermal reactive vascular proliferation was the most common dermal change (32%). CONCLUSIONS: NUC is more common than previously reported and shows a higher predilection for obese postmenopausal women. Undiagnosed hyperparathyroidism shows a possible association with NUC. Lupus anticoagulants were positive in most patients. NUC biopsies are more likely than UC biopsies to display extravascular calcium deposition.

Dynamic heterogeneity of cerebral hypoperfusion after prolonged cardiac arrest in dogs measured by the stable xenon/CT technique: a preliminary study.

After prolonged cardiac arrest and reperfusion, global cerebral blood flow (gCBF) is decreased to about 50% normal for many hours. Measurement of gCBF does not reveal regional variation of flow or permit testing of hypotheses involving multifocal no-flow or low-flow areas. We employed the noninvasive stable Xenon-enhanced Computerized Tomography (Xe/CT) local CBF (LCBF) method for use in dogs before and after ventricular fibrillation (VF) cardiac arrest of 10 min. This was followed by external cardiopulmonary resuscitation (CPR) and control of cardiovascular pulmonary variables to 7 h postarrest. In a sham (no arrest) experiment, the three CT levels studied showed normal regional heterogeneity of LCBF values, all between 10 and 75 ml/100 cm3 per min for white matter and 20 and 130 ml/100 cm3 per min for gray matter. In four preliminary CPR experiments, the expected global hyperemia at 15 min after arrest, was followed by hypoperfusion with gCBF reduced to about 50% control and increased heterogeneity of LCBF. Trickle flow areas (LCBF less than 10 ml/100 cm3 per min) not present prearrest, were interspersed among regions of low, normal, or even high flow. Regions of 125-500 mm3 with trickle flow or higher flows, in different areas at different times, involving deep and superficial structures migrated and persisted to 6 h, with gCBF remaining low. These preliminary results suggest: no initial no-reflow foci (less than 10 ml/100 cm3 per min) larger than 125 mm3 persisting through the initial global hyperemic phase; delayed multifocal hypoperfusion more severe than suggested by gCBF measurements; and trickle flow areas caused by dynamic factors.

Xenon-enhanced computed tomography compared with [14C]iodoantipyrine for normal and low cerebral blood flow states in baboons.

The correlation between the acute, invasive diffusible [14C]iodoantipyrine technique for cerebral blood flow and the noninvasive xenon-enhanced computed tomographic method has been assessed by simultaneous measurements in the baboon. Blood flows in small tissue volumes (about 0.125 cm3) were directly compared in normal and low flow states. These studies demonstrate a statistically significant association between the two methods (p less than 0.001). Similar correlations were obtained by both the Kendall (tau) and the Spearman (r) methods (r = 0.67 to 0.92, n greater than or equal to 19 for each study). The problems and limitations of such correlations are discussed.

Autoregulation remains intact during stable xenon inhalation in the baboon.

To test the possible effect of 32% end-tidal Xe concentration upon autoregulation, 5 baboons, Papio anubis/cynocephalus, were anesthetized/paralyzed with propranolol 0.02, diazepam 0.1, morphine sulfate 0.1, and pancuronium 0.2 (mg/(h.kg)). The animals were subjected to a servocontrolled blood infusion-withdrawal program to control central aortic blood pressure (CAP). PaCO2 was held to 30 to 35 torr, with individual variation less than 3 torr by control of ventilation and by including CO2 in the Xe/O2 mixture. Three to six CBF measurements were made in each subject over the above range. In four animals the CAP was varied between 18 and 150 torr, with corresponding CBF measurements. The CAP range was extended to 196 torr in the 5th animal by IV administration of phenylephrine. Significant lowering of global blood flow did not occur above 40 torr mean CAP. While regulated flow persists to about 150 torr at the high end, there is a breakaway between 150 and 190 torr where flow increased 90%. A 4th order polynomial fit of the data has the characteristic appearance of the familiar autoregulation curve. We conclude that autoregulation is preserved even in the presence of FIXe of 32% in the breathing mixture.

Shoulder Antagonistic Strength Ratios: A Comparison between College-Level Baseball Pitchers and Nonpitchers.

The purpose of this study was to investigate the shoulder strength ratios obtained from college-level baseball pitchers and age- and sex-matched nonpitchers. Shoulder flexion/extension and externallinternal rotation strength ratios were assessed in 10 pitchers and 9 nonpitchers. Speeds selected for testing were 180 and 300 degrees /sec on the Cybex /I.@R esults indicated that both pitchers and nonpitchers generated greater peak torque values for the extensors and internal rotators than for the flexors and external rotators of the shoulder. A comparison of shoulder strength ratios between a pitcher's throwing arm and his nonthrowing arm was statistically significant (p < 0.05) for shoulder external/internal rotation at the speeds of 180 and 300 "/set. A comparison of shoulder strength ratios between pitchers and nonpitchers on the nondominant arm was not statistically significant for any of the speeds or directions tested. A comparison of the shoulder strength ratios between pitchers and nonpitchers on the dominant arm was statistically significant (p < 0.05) for all directions and speeds tested. The relationship between shoulder muscle imbalance and injury was discussed. J Orthop Sports Phys Ther 1987;8(9):451-461.

Mechanical and metallurgical properties of carotid artery clamps.

The mechanical and metallurgical properties of carotid artery clamps were evaluated. The pressure plate retreat propensity, metallurgical composition, surface morphology, magnetic properties, and corrosion resistance of the Crutchfield, Selverstone, Salibi, and Kindt clamps were tested. None of the clamps showed evidence of pressure plate retreat. The clamps differed significantly in their composition, surface cleanliness, magnetic properties, and corrosion resistance. The Crutchfield clamp was the only one manufactured from an ASTM-ANSI-approved implantable stainless steel (AISI 316) and the only clamp in which the surfaces were clean and free of debris. The Selverstone clamp was made principally from AISI 304 stainless steel, as was one Salibi clamp. The pressure plate on another Salibi clamp was made from a 1% chromium and 1% manganese steel. Machining and surface debris consisting principally of aluminum, silicon, and sulfur was abundant on the Selverstone and Salibi clamps. The Kindt clamp was manufactured from AISI 301 stainless steel with a silicate-aluminized outer coating. The Crutchfield and Selverstone clamps were essentially nonferromagnetic, whereas the Salibi and Kindt clamps were sensitive to magnetic flux. In the pitting potential corrosion test, the Crutchfield clamp demonstrated good corrosion resistance with a pitting potential of 310 mV and no surface corrosion or pitting by scanning electron microscopy examination. The Selverstone clamp had lower pitting potentials and showed various degrees of corrosion and surface pitting by scanning electron microscopy. The Salibi pressure plate had a very low pitting potential of -525 mV and showed severe corrosion. By metallurgical criteria, only the Crutchfield clamp is suitable for long term implantation.

Simultaneous measurements of cerebral blood flow by the xenon/CT method and the microsphere method. A comparison.

Simultaneous measurements of cerebral blood flow have been performed in baboons to assess the correlation between the acute and invasive nondiffusible microsphere technique and the noninvasive xenon-enhanced CT method. Blood flows in small tissue volumes (approximately 1 cm3) were directly compared. The results of these studies demonstrate a statistically significant association between the two methods (P less than .001). Similar correlations were obtained by both the Kendall tau (tau) and the Spearman (r) methods. The problems and limitations of such correlations are discussed.

Measurement of cerebral blood flow during xenon inhalation as measured by the microspheres method.

Measurements of cerebral blood flow (CBF) were performed using the microsphere technique in non-human primates (baboons) to assess the effect of non-radioactive xenon gas inhalation on CBF. Blood flows in small tissue volumes (approximately 1 cm3) were directly measured before and during the inhalation of xenon/oxygen gas mixtures. The results of these studies demonstrated that when inhaled in relatively high concentrations, xenon gas does increase CBF, but the changes are more global than tissue-specific. The problems and limitations of such evaluations are discussed.

Neurogenic hypertension: etiology and surgical treatment. II. Observations in an experimental nonhuman primate model.

In a companion paper (Ann Surg 1985; 201(3):391-398), clinical data which suggest that neurogenic hypertension may be caused by arterial compression of the left medulla oblongata was presented. A chronic pathophysiologic animal model of neurogenic hypertension using a substitute for arterial pulsation, the neurovascular compression simulator (NCS), was developed. This paper presents data that demonstrate how development of hypertension in a nonhuman primate baboon (5 subject animals, 5 control animals) can be caused by the NCS, and the blood pressure can subsequently return to normal following cessation of NCS activity. These experiments show that pulsatile compression of the left ventrolateral medulla oblongata results in cardiovascular changes consistent with the sequence found in human neurogenic hypertension. Arteriosclerosis and arterial ectasia in the human contribute to arterial elongation and looping at the base of the brain. An arterial loop, by causing pulsatile compression of neural structures, elicits an increase in blood pressure initiated by an increase in cardiac output. This may be due to interference with the autonomic control of the heart and/or by alteration of the relative capacitance of the vascular system.

Xenon/CT blood flow mapping of the kidney and liver.

A noninvasive technique for measuring blood flow by xenon-enhanced X-ray transmission CT has been developed and reported quite extensively in recent years. In this method nonradioactive xenon gas is inhaled, and the temporal changes in radiographic enhancement produced by the inhalation are measured by sequential CT. Time-dependent xenon concentration within various tissue segments is used to derive local blood flow maps. The method has been amply discussed in relation to assessment of local cerebral blood flow. Its application to other body organs is explored in this paper, in which results from six preliminary blood flow studies in the liver and kidneys of nonhuman primates are reported. Blood flow in renal cortex ranged from 150 to 280 ml/100 cc/min and hepatic tissue perfusion from 80 to 120 ml/100 cc/min. The advantages and limitations of the method in such applications are discussed.

Lack of effect of serotonin and norepinephrine on CRF release from hypothalami in vitro.

A number of investigations utilizing hypothalami from adrenalectomized animals have provided conflicting results regarding the role of serotonin (5HT) and norepinephrine (NE) in CRF regulation. In order to further investigate these neurotransmitters, we performed three sets of experiments with hypothalami obtained from intact rats. In experiment I, freshly obtained rat hypothalami were randomly grouped and incubated in control medium and medium in the presence of 10(-11) M, 10(-10) M, and 10(-9) M serotonin. Aliquots of 200 microliters of these incubates were bioassayed for CRF activity using a dispersed anterior pituitary cell system, and ACTH secretion from the cells was determined by radioimmunoassay. A preliminary experiment had determined that a 200 microliters aliquot from hypothalami incubated in control medium resulted in a significantly (p less than 0.0001) greater ACTH release than obtained from cells alone. No significant effect of serotonin on hypothalamic CRF release was obtained. In experiment III, individual hypothalami were bisected longitudinally, and one half served as control. The contralateral half was incubated in medium containing 10(-11) M, 10(-10) M, and 10(-9) M serotonin. CRF release in this experiment again revealed no significant effect of serotonin. In experiment II, hypothalami were again randomly grouped and incubated with control medium and in the presence of 10(-8) M and 10(-6) M norepinephrine. This experiment resulted in no significant effect of norepinephrine on CRF release. These results suggest that serotonin and norepinephrine at the concentrations studied have no effect on CRF release from hypothalami obtained from intact rats.

Progress in cerebrovascular disease: local cerebral blood flow by xenon enhanced CT.

A noninvasive technique for measuring local cerebral blood flow (LCBF) by xenon enhanced x-ray transmission computed tomography (CT) has been developed an reported quite extensively in recent years. In this method, nonradioactive xenon gas in inhaled and the temporal changes in radiographic enhancement produced by the inhalation are measured by sequential computed tomography. Time dependent xenon concentrations within various tissue segments in the brain are used to derive both local partition coefficient (lambda) and LCBF. An assessment of this method reveals that although it provides functional mapping of blood flow with excellent anatomic specificity, there are distinct limitations. The assumptions underlying this methodology are examined and problems associated with various potential applications of this technique are discussed.

Implanted pulsatile balloon device for simulation of neurovascular compression syndromes in animals.

A self-contained neurovascular compression simulator (NCS) has been designed to function as an artificial artery that pulsates with the heart. When implanted in animals, this device simulates those naturally occurring situations in which there is compression of nervous elements in the region of the brain stem or other areas by aberrant, or ectatic branches of normal arteries. The NCS consists of an intra-aortic balloon, a smaller (cephalic) balloon, a connecting tube, and an injection port, all fabricated of polyurethane-silicone compounds. With each heart systole, the rise in intra-aortic pressure is transmitted to the smaller cephalic balloon in the form of a pulsation. Thus, part of the cardiac ejection energy is transferred to the desired nervous structures. The performance of each NCS is tested in vitro in a pulse duplicator system. The NCS was chronically implanted for up to 2 years in four dogs and 10 baboons. The cephalic balloon was placed intracranially in the subarachnoid space on the ventrolateral medulla adjacent to the entry zone of the ninth and 10th cranial nerves on the left side of baboons and on the right side of dogs. The position of the balloons was checked by fluoroscopy. Following implantation, the NCS could be inflated or deflated at will using the injection port which served to restart or discontinue the pulsations. No occlusion of the aorta or reduction of blood flow to the lower limbs or trunk was detected. By means of the NCS, an experimental model of neurogenic hypertension was produced in baboons.

Running elevates plasma beta-endorphin immunoreactivity and ACTH in untrained human subjects.

Twenty minutes of submaximal treadmill running was associated with an elevation in plasma levels of beta-endorphin immunoreactivity (P less than 0.02). This increase was greater in men (14.9 +/- 3.4 fmole/ml) than women (2.6 +/- 1.2 fmole/ml)(P less than 0.05). Plasma levels of ACTH and growth hormone also increased after running. ACTH increased more in men (7.8 +/- 1.1 fmole/ml) than in women (1.1 +/-0.44 fmole/ml)(P less than 0.02). There was a similar growth hormone response in both sexes. No correlation can at this time be made with levels in the central nervous system. Changes in plasma levels of beta-endorphin immunoreactivity may be responsible for some of the euphoria and analgesia anecdotally associated with running.

Side effects of xenon inhalation.

Short- and long-term side effects during and after inhalation of premixed xenon oxygen (28-47%) from 12 studies are reported. While all but one subject tolerated xenon inhalation without ill effects, that individual did experience unpleasantly severe dysesthesias and a brief period of unresponsiveness. We believe that further human studies with xenon inhalation should be conducted to explore possible early indicators for reduced tolerance of xenon by certain individuals.

Abnormality of the xenon brain:blood partition coefficient and blood flow in cerebral infarction: an in vivo assessment using transmission computed tomography.

Xenon-enhanced computed tomography (CT) was used to analyze, in vivo, the patterns of blood flow of cerebral infarction in a nonhuman primate model. Consistent and reproducible results were attained utilizing the numerical data from CT scans obtained during the inhalation of nonradioactive xenon. The spatial resolution of CT defined a morphophysiologic map of the variability in brain:blood partition coefficient and flow rate constant that exist within and around an infarct. Both the flow and the partition coefficient were significantly diminished in the ischemic focus in all animals studied. Although the partition coefficients were normal, the flow was decreased in the other locales sampled in the ipsilateral hemispheres. In the contralateral hemispheres, both flows and partition coefficients were within the range of normal for adolescent baboons.

Experimental xenon enhancement with CT imaging: cerebral applications.

Xenon-enhanceed cranial computed tomography (CT) was used to derive the partition coefficient (lambda) and flow rate constant (kappa) and thus provide a functional neuroanatomic map of local cerebral blood flow in eight nonhuman primates. Sequential CT imaging defined the temporal changes of xenon concentration in arterial blood and brain tissue both during and after xenon inhalation. Several methodologies including clearance, buildup, and in vivo "autoradiography" were used to estimate flow in various brain locales. A typical derived fast flow rate using xenon CT methodology was 85 ml/100 g/min, with a range of 58--108. The in vivo autoradiographic method of defining flow seems more clinically applicable in man. The limitations and potential solutions using CT blood flow techniques are discussed.

Comparative cranial CT enhancement in a primate model of cerebral infarction.

The value of various enhancement techniques as opposed to nonenhanced CT scanning was compared in 15 baboons with cerebral infarction secondary to embolization of the left middle cerebral artery. The most prominent CT findings in infarction included an area of low absorption in the opercula--basal ganglia--centrum semiovale region and generalized lateral ventricular enlargement. Intravenous enhancement of the low-density region occurred in 25% of the animals and often obscured the preenhancement abnormality. However, a rapid bolus injection of contrast material followed by immediate consecutive CT scans (computed angiotomography) permitted prominent visualization of early-shunting veins. Delayed scanning following intrathecal enhancement better defined small infarctions that did not exhibit the usual cerebral blush. The CT imaging of inhaled xenon provides a new technique for evaluating subtle abnormalities in cerebral perfusion, even when the routine CT scan shows no abnormality.

Comparative cranial CT enhancement in the normal primate.

The application of intravenous, intrathecal, and inhalation enhancement techniques to the CT evaluation of the nonhuman primate (Papio cynocephalus/anubis) is described. The falx cerebri cortical vasculature, vein of Galen, straight sinus and tentorium cerebelli were defined with intravenous enhancement. Intrathecal CT enhancement with air was limited by distortion in cerebrospinal fluid spaces. Intrathecal CT enhancement using a low dose of metrizamide accurately delineated the subarachnoid spaces and the brain substance they surrounded with minimal morbidity. Symmetrical brain enhancement (perfusion) was prominent following inhalation CT enhancement; the degree of enhancement correlated with the estimated xenon concentration in the bloodstream. In addition, by performing repeated CT scans during the clearance of xenon from the brain, an approximate analysis of regional cerebral blood flow was obtained.

Xenon enhanced CT for analysis of cerebral integrity, perfusion, and blood flow.

Enhancement of the brain substance for CT evaluation using inhaled Xenon is confirmed. This technique was applied to the study of the normal and the embolized adolescent baboon. Healthy cerebral tissue enhances symmetrically, while abnormal areas show significantly diminished enhancement. At maximal enhancement, an indication of gross comparative cerebral perfusion to obtained. By obtaining serial CT scans over a 10 minute time interval, the clearance rate of Xenon (cerebral blood flow) may be evaluated. Xenon-enhanced CT enables a visual and numerical analysis of both brain morphology and physiology.