IL-15 improves skeletal muscle oxidative metabolism and glucose uptake in association with increased respiratory chain supercomplex formation and AMPK pathway activation.

BACKGROUND: IL-15 is believed to play a role in the beneficial impact of exercise on muscle energy metabolism. However, previous studies have generally used supraphysiological levels of IL-15 that do not represent contraction-induced IL-15 secretion. METHODS: L6 myotubes were treated acutely (3 h) and chronically (48 h) with concentrations of IL-15 mimicking circulating (1-10 pg/ml) and muscle interstitial (100 pg/ml -20 ng/ml) IL-15 levels with the aim to better understand its autocrine/paracrine role on muscle glucose uptake and mitochondrial function. RESULTS: Acute exposure to IL-15 levels representing muscle interstitial IL-15 increased basal glucose uptake without affecting insulin sensitivity. This was accompanied by increased mitochondrial oxidative functions in association with increased AMPK pathway and formation of complex III-containing supercomplexes. Conversely, chronic IL-15 exposure resulted in a biphasic effect on mitochondrial oxidative functions and ETC supercomplex formation was increased with low IL-15 levels but decreased with higher IL-15 concentrations. The AMPK pathway was activated only by high levels of chronic IL-15 treatment. Similar results were obtained in skeletal muscle from muscle-specific IL-15 overexpressing mice that show very high circulating IL-15 levels. CONCLUSIONS: Acute IL-15 treatment that mimics local IL-15 concentrations enhances muscle glucose uptake and mitochondrial oxidative functions. That mitochondria respond differently to different levels of IL-15 during chronic treatments indicates that IL-15 might activate two different pathways in muscle depending on IL-15 concentrations. GENERAL SIGNIFICANCE: Our results suggest that IL-15 may act in an autocrine/paracrine fashion and be, at least in part, involved in the positive effect of exercise on muscle energy metabolism.

Stability of values for thyroid radioiodine uptake.

UNLABELLED: Chronological changes in values for thyroid radioiodine uptake measurements (RIU) have been reported in the last four decades. These changes are attributed to geographical and chronological variations in dietary iodine intake in the population. Fluctuations in normal values for RIU can affect the interpretation of these diagnostic tests in patients. METHODS: During the last 16 yr, thyroid RIU measurements using 123I were obtained in 671 euthyroid patients and 274 hyperthyroid patients, of which 233 patients had a diffuse goiter and 41 patients had a nodular goiter. RIU was measured 24 hr after the oral administration of 123I, 3.7-7.4 MBq (0.1-0.2 mCi) with no changes in technique during this period. Values (mean +/- s.d.) for RIU were calculated for various groups of patients for each year. Combined data for 1979-83 and 1988-94 were compared. Differences between mean values for each year were determined by a one-way ANOVA and pairwise comparison. RESULTS: For euthyroid patients, there were no significant differences in the mean and range of values from year to year. Additionally, there were no significant differences between the combined values for the earlier years (1979-83) and the later years (1988-94) for hyperthyroid patients. Minor statistical variations in the yearly values for the hyperthyroid patients were evident but not clinically important. CONCLUSION: Values for thyroid uptake of 123I in euthyroid and hyperthyroid patients in Boston have remained stable for the last 16 yr.

Outcome of pregnancy in diabetic ketoacidosis.

To evaluate the outcome of pregnancy in diabetic women who had an episode of ketoacidosis during gestation, 20 consecutive cases of ketoacidosis in type I diabetic pregnant women were studied. They were divided into two groups for comparison: Group 1, 13 patients (65%), had a live fetus and group 2, seven patients (35%), had a fetal death on admission. Both groups were similar in age, gravidity, parity, abortions, height, weight, serum sodium and potassium, arterial pH, carbon dioxide tension, bicarbonate, base excess, and anion gap. Significantly different between groups 1 and 2 were: gestational age (24 versus 31 weeks; p < 0.05), serum glucose (374 versus 830 mg/dl; p < 0.005), blood urea nitrogen (14 versus 23 mg/dl; p < 0.025), osmolality (295 versus 311 mmol/kg; p < 0.025), insulin requirements (127 versus 202 U; p < 0.05), and length of resolution (28 versus 38 hours; p < 0.05). Two patients had serum glucoses less than 200 mg/dl despite profound ketoacidosis. Precipitating factors included infections, poor compliance, and very importantly, unrecognized new onset of diabetes (6 patients). All stillborns were grossly normal and those autopsied had no discernible cause of death. There were no maternal deaths. A high fetal mortality (35%) was found but there were no fetal losses once therapy was initiated. The unrecognized new onset diabetics accounted for almost a third (30%) of the cases of ketoacidosis and for 57% of the fetal deaths. Attentiveness to the symptoms of uncontrolled diabetes and appropriate screening can be effective preventive measures.

Clinical indicators and their role in quality management.

In this paper the authors look at the proactive role performance indicators can and should play in managing for quality in health care facilities. In particular, they highlight the use of clinical indicators as a means of providing evidence of value-for-money and best quality delivery of care. The argument is presented that management can no longer ignore indicators as a quality assurance tool and an important component of managing for quality over time. The authors demonstrate where indicators fit into the traditional quality assurance cycle and describe strategies for analysing problems and setting priorities. They also argue that managers need to invest in management information systems in order to provide the data needed for performance monitoring. Accurate and complete indicator data are needed if the goals of quality management and optimal quality of care are to be achieved.

Early effects of ethylene glycol on the ultrastructure of the renal cortex in dogs.

A sublethal dose of ethylene glycol was administered orally to 3 groups of dogs; dogs of a control group were given distilled water instead. Renal cortical biopsy samples were obtained from dogs of experimental and control groups at various times after treatment. Tissue was examined by use of light microscopy and transmission electron microscopy. In dogs of the control group, the light and electron microscopic appearances of tissue were within normal limits at all sample collection hours. In dogs of the experimental groups, renal corpuscular structure remained within normal limits by use of light and electron microscopy throughout the study, though morphologic change was seen in other structures of the cortex. Light microscopic lesions first appeared at 12 hours, and were similar to those reported in the literature. Ultrastructural lesions were first observed in the 5-hour samples, and similar to the light microscopic lesions, were most common in the proximal convoluted tubules (PCT). Initial PCT cellular changes included vacuolization of cells and distention of the parabasal extracellular spaces; PCT cellular lesions seen in later-hour samples included formation of apical buds and cellular rupture. Internalization or sloughing of the PCT brush border was not observed. Distal convoluted tubules (DCT) were frequently dilated and/or packed with cellular debris. A few DCT cells had degenerative or necrotic changes. In PCT and DCT, abnormal cells were frequently flanked by normal or nearly normal cells. During later hours, a few cells with types of changes first observed in early hours continued to be observed, implying ongoing response of cells to the toxin.

Comparative mucosal microvasculature of the mammalian stomach.

The comparative morphology of the gastric mucosal microvasculature was investigated using the corrosion casting technique. The vascular pattern consisted of a hexagonally arranged capillary plexus surrounding the gastric glands and terminating in venules running perpendicular to the mucosal axis. Vessels of the pyloric antrum demonstrated an acute angle between capillaries and venules, whereas vessels of the gastroduodenal junction changed from a honeycomb pattern to a leaf-like arrangement.

Arterial supply and venous drainage of the brain of the black bear (Ursus americanus). I. Gross anatomical distribution.

A morphological study of the intracranial vessels of the Black bear (Ursus americanus) was undertaken. The object was to provide basic information related to the vascular pattern in these animals as compared with other carnivores and with the human. Vascular casts were prepared from 6 animals. The vasculature of the brain disclosed patterns comparable to other species previously studied.

Arterial supply and venous drainage of the brain of the black bear (Ursus americanus). II. Intracranial microvasculature.

A morphological study of the intracranial microvasculature of the Black bear (Ursus americanus) using vascular casts was undertaken. The object was to provide basic information regarding structural modifications of the microvasculature that might provide insight into the ability to cope with low blood flow states that occur during winter sleep. Vascular casts were prepared from 6 animals. The microvasculature of the brain disclosed characteristic features of the small vessels in mammals, including vascular sphincters of two types and numerous arterial and arteriolar anastomoses.

Microvasculature of the bear heart demonstrated by scanning electron microscopy.

Morphological features of the coronary microvasculature were examined in ten Black bears (Ursus americanus). Tissue samples were collected for scanning electron microscopy from five animals, and vascular casts of the coronary vessels were prepared from five. Each portion of the microvasculature examined had specific morphological characteristics which may contribute to the control of blood flow. All indications from the present study suggest that the structure of the coronary microvasculature in the Black bear is similar to that of mammalian species previously examined.

Renal microvasculature of the black bear (Ursus americanus).

This study of the Black bear (Ursus americanus) was undertaken to provide basic information related to structural modifications in the renal microvasculature that might provide insight into the drastic alteration in renal urinary output that occurs during winter sleep. Vascular casts, as well as light microscopy and scanning electron microscopy, were used to study the vascular components of the juxtaglomerular complex and related vessels. Histologically, arterial cushions were readily identified at the origin of the afferent arterioles. In the area of the juxtaglomerular complex, the wall of the afferent arteriole appeared to be highly modified. The smooth muscle cells at this site demonstrated a change in morphology and orientation, and the diameter of the arteriole was altered. The pattern of the vascular casts at the origin of the afferent arteriole varied from that portion at the glomerulus, suggesting a modification of the vascular wall near the renal corpuscle. Although the morphology of the renal microvasculature of the Black bear is similar to that of other mammals in some aspects, it is dissimilar to that of other carnivores and of the human kidney in that there are structural modifications of the afferent arteriole that may contribute to a reduction of blood flow to the nephron during winter sleep.

Lithium and lecithin in tardive dyskinesia: an update.

Psychiatric inpatients with tardive dyskinesia (TD) were treated with either lithium alone (n = 9) or with a combination of lithium and lecithin (n = 9) for 5 weeks in a double-blind, placebo-controlled experiment. A statistically significant but clinically unimportant improvement of TD occurred during both treatments. The addition of lecithin to lithium had no effect.

Cholecystitis secondary to infusion chemotherapy.

This report centers on a patient with metastatic colorectal cancer who developed acute and chronic cholecystitis secondary to the infusion of FUDR (fluoro-deoxyuridine) into the hepatic artery. This was documented by sonography, cholescintigraphy, and, ultimately, pathologically on the surgically removed specimen. Undoubtedly, with increasing cumulative treatment days made possible through technological advances in delivery systems, this complication will be seen more frequently. Prophylactic removal of the gallbladder, at the time of pump placement, which does not significantly prolong the operative time nor increase the operative mortality, should be performed to prevent this complication from occurring.

Vascular pathways of the anterior segment of the canine eye.

The vasculature of the anterior segment of the canine eye was studied by preparing intravascular casts with a methyl methacrylate resin. Specimens were examined and results were recorded with the aid of stereoscopic dissecting and scanning electron microscopes. The arterial supply was via anterior ciliary and long posterior ciliary arteries. An arterial circle derived from dorsal and ventral anterior ciliary arteries was identified in the anterior sclera. The long posterior ciliary artery contributed branches to the choroid, anterior sclera, and anterior border of the ciliary processes. Radial iris arterioles arose from the major arterial circle of the iris and ended blindly at the pupillary margin. Radial ciliary arteries arose from the major arterial circle of the iris and ran posteriorly and supplied the ciliary processes and muscle and fused with the choroidal vasculature. Each ciliary process was supplied by an afferent arteriole from the radial ciliary artery. Sphincters could be seen at branch points within the vascular net of the ciliary processes.

Intracapsular and intraosseous vascular supply to the mature dog's coxofemoral joint.

The intracapsular and intraosseous arterial supply to the mature dog's coxofemoral joint was investigated using a vascular injection, tissue-clearing technique in 6 mixed-breed dogs. Ascending arteries of the femoral neck, arising from an extracapsular vascular ring at the base of the femoral neck, penetrated the articular capsule and traveled subsynovially over the surface of the femoral neck. These intracapsular arteries formed an incomplete intracapsular vascular ring at the junction of the femoral head and neck. Bony components of the acetabulum, ie, ilium, ischium, and acetabular bones, received intraosseous vascular supply from the nutrient artery of the ilium and minute vessels entering nutrient foramina around the rim of the acetabulum. The femoral head received branches (epiphyseal arteries) from the ascending arteries of the femoral neck at the intracapsular vascular ring. Epiphyseal arteries formed anastomosing vascular arches of decreasing caliber up to the subchondral bone of the femoral head. The proximal femoral metaphysis, particularly the femoral neck, received vascular supply from 4 sources: (i) branches from the epiphyseal arteries on the surface of the physeal scar which descended, penetrating the physeal scar, (ii) distally directed branches from the intracapsular vascular ring, (iii) ascending nutrient vessels from the trochanteric fossa, and (iv) terminal branches of the ascending nutrient artery of the femur.

Extraosseous vascular supply to the mature dog's coxofemoral joint.

Blood vessels supplying the coxofemoral joint were identified and described in 8 healthy, mature dogs. An accurate representation of the blood vessels was obtained by intra-arterial methyl methacrylate injection and sodium hydroxide corrosion of soft tissues until only the pelvis, femurs, and casts of the blood vessels remained. The sources of vascular supply to the dog's coxofemoral joint, from most to least contributory, were the lateral circumflex femoral artery, the medial circumflex femoral artery, the caudal gluteal artery, the cranial gluteal artery, and the iliolumbar artery. In addition, important vascular relationships were demonstrated. Many blood vessels were associated with the periosteal surfaces of the coxofemoral joint in areas of muscular and articular capsular attachment; fewer vessels were present in areas of loose periosteal attachment. Also, extra-articular anastomoses were identified. The most significant anastomosis was an extracapsular vascular ring located at the femoral attachment of the articular capsule. The extracapsular vascular ring was formed by branches of the lateral and medial circumflex femoral and caudal gluteal arteries.