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Objective: The Low Molecular Weight Fraction of 5% human serum Albumin (LMWF-5A) is being investigated as a treatment for knee pain from osteoarthritis., Methods: This was a multicenter randomized, vehicle-controlled, double-blind, parallel study designed to evaluate the safety and efficacy of two doses of an intra-articular injection of LMWF-5A. Patients with symptomatic knee osteoarthritis were randomized 1∶1∶1∶1 to receive a single 4 mL or 10 mL intra-articular knee injection of either LMWF-5A or vehicle control (saline). The primary efficacy endpoint was the difference between treatment groups in the Western Ontario and McMaster Universities (WOMAC) pain change from baseline over 12 weeks. Safety was examined as the incidence and severity of adverse events (AEs)., Results: A total of 329 patients were randomized and received treatment. LMWF-5A resulted in a significant decrease in pain at 12 weeks compared to vehicle control (-0.93 vs -0.72; estimated difference from control: -0.25, p = 0.004); an injection volume effect was not observed (p = 0.64). The effect of LMWF-5A on pain was even more pronounced in patients with severe knee OA (Kellgren Lawrence Grade IV): the estimated difference from control was -0.42 (p = 0.02). Adverse events were generally mild and were similar in patients who received vehicle control (47%) and LMWF-5A (41%)., Conclusions: This clinical trial demonstrated that LMWF-5A is safe and effective at providing relief for the pain of moderate to severe OA of the knee over 12 weeks when administered by intra-articular injection into the knee., Trial Registration: ClinicalTrials.gov NCT01839331.

Langerhans cell histiocytosis of the head and neck is an uncommon histiocytic proliferative disorder that often clinically resembles an inflammatory process. A pseudoaneurysm of the external carotid artery was found by contrast-enhanced CT and confirmed by Doppler ultrasonography and angiography in a 9 year old girl with a lytic lesion of the mandible, a prior severe tracheal inflammatory process, and sclerotic lesions of the sphenoid wings. Biopsies of the mandibular lesion, pseudoaneurysm, and trachea demonstrated Langerhans cell histiocytosis. In cases of LCH with head and neck involvement, contrast-enhanced CT allows adequately detailed initial evaluation of the protean manifestations of this disorder.

Peripheral resistance was examined in the microcirculation of the rat cremaster muscle using a network-conserved parameter, power dissipation. Previous studies of peripheral resistance used network-sensitive parameters, and their interpretation is limited by tacit assumptions about the structure of the peripheral vasculature. Power dissipation is directly linked to the resistive process, providing a measure of resistance based on the actual hemodynamics of the network. The dissipation parameter was quantified with the usual vascular parameters of velocity and vessel segment length; 991 segment lengths were measured in 12 normotensive Wistar-Kyoto rats and 16 spontaneously hypertensive rats. Arterial power dissipation was significantly elevated over a wide range of vessel segments; blood flow ranged from 0.08 to 80 nl/sec. Since the largest vessels showed the greatest power dissipation, the organ resistance elevation seen in hypertension in the cremaster apparently is mediated by the larger vessels in the high flow range. Vessel segment length and number of dissipative vessels were unchanged. The increase in power dissipation was due to a network-averaged reduction in mean vessel diameter. Power dissipation also increased significantly in the fastest flowing venous microvessels (greater than 25 nl/sec), also due to a reduction in vessel segment diameter.

This study investigated the microvascular changes that affect vascular resistance in the rat small intestine during two-kidney, one clip renal hypertension 4 weeks after renal artery stenosis. To study the intestinal microcirculation, a loop of the small intestine was exteriorized with intact circulation and innervation and a section of the bowel wall was prepared for observation with an intravital video microscopy system. Microvascular diameter, pressure, and flow velocity were measured for first, second, and third branch order arterioles and venules, using an image shearing monitor, servo-null micropipette system, and an optical Doppler velocimeter, respectively. The diameters of the first order arterioles and venules were significantly (p less than 0.05) reduced in hypertensive rats; however, diameters were unaltered in smaller second and third order arterioles and venules as compared with normotensive vessels. In hypertensive rats, mean arterial pressure was significantly (p less than 0.05) elevated (47%) and pressures also were elevated significantly (p less than 0.05) throughout the microcirculation, although by a proportionally smaller amount. Total network flow (i.e., first order arteriole flow) was significantly (p less than 0.05) reduced (40%) in hypertensive rats, but volume flows in individual second and third order arterioles were similar to flows measured in normotensive rats. Calculated total network resistance was increased (124%) in hypertensive rats. Thus, the intestinal microcirculation in rats with two-kidney, one clip renal hypertension is disturbed by elevated pressure and decreased total flow. The presence of normal flows in individual second and third order arterioles without any demonstrable difference in their diameters suggests that the predominant cause of elevated resistance across this segment of the intestinal microcirculation is a reduction in the number of perfused small arterioles.

A glycoprotein molecule discovered in pituitary glands of experimental animals is thought to be the precursor molecule for the pituitary peptides ACTH and beta-lipotropin, molecules themselves known to contain the amino acid sequences of several smaller peptides subsequently isolated. Evidence now exists to suggest the enzymatic cleavage of ACTH to alpha-MSH and corticotropic-like intermediate lobe peptide (CLIP), pituitary peptides with effects upon the fetal pituitary gland. Beta-lipotropin is probable the prohormone for the peptides beta-MSH, gamma-lipotropin, methionine-enkephalin, and beta-endorphin. Beta-MSH may enchance the known physiologic effects of mammalian central nervous system transmitters, while the enkephalins and beta-endorphin have been shown to exhibit opioid analgesic properties as well as effects upon behavior, temperature regulation, and the release of growth hormone and prolactin. Homologies among their amino acid sequences and evidence for prohormone activity in ACTH, beta-lipotropin, and the putative ACTH-beta lipotropin precursor suggest the possibility of the presence of a previously unsuspected interrelationship in the synthesis and release of these various pituitary peptides.

A new sensing unit has been designed for intravital velocimetry using cross-correlation techniques. Using a photodiode and low-noise operational amplifier, residual noise has been greatly reduced. At low light levels with equal-frequency passbands, signal-to-noise ratios are improved by greater than a factor of 10. Part of the improvement has been traded for increased frequency range that will allow accurate measurements of velocity 10 to 100 times greater than the unit that was used previously. The precise upper limit for flow velocity measurement with the modified unit will depend on factors such as the spatial fine structure of the RBC column and the digital sampling of the cross-correlation unit, but a cursory examination indicates that most flow velocities in the microcirculation can be measured. The increased frequency range combined with light-level-independent characteristics will greatly improve the accuracy of RBC velocity measurements made in vivo.

A system has been implemented for measurement of red blood cell velocity in microvessels by using an optical Doppler technique. Ronchi rulings are used to stimulate a differential grating to translate red blood cell movement to light intensity variations. These variations are sensed by two photodiodes coupled in a resistive subtraction mode. The nonelectronic subtraction allows high transimpedance gains (2 X 10(9) V/I) while noise is held to a minimum (4.5 mv RMS in a 5-kHz bandwidth). To derive average velocity the average frequency determination of the amplified signal is performed with a thresholding frequency-to-voltage functional block. The velocimeter provides the typical performance features of an optical Doppler system, including high-frequency response, without the need for the complications of the laser Doppler technique or the requirement of custom micro-prism gratings. The device represents a cost-effective approach to intravital work, and offers significant improvements in performance over standard techniques.