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Background: Treatment of diabetes costs the United States an estimated $245 billion annually; one-third of which is related to the treatment of diabetic foot ulcers (DFUs). We present a safe, efficacious, and economically prudent model for the outpatient treatment of uncomplicated DFUs., Methods: 77 patients (mean age = 54 years, range 31 to 83) with uncomplicated DFUs prospectively enrolled from September 2008 through February 2012. All patients received an initial sharp debridement by one of two orthopaedic foot and ankle fellowship trained surgeons. Ulcer dressings, offloading devices, and debridement procedures were standardized. Patients were evaluated every two weeks by research nurses who utilized a clinical management algorithm and performed conservative sharp wound debridement (CSWD)., Results: Average time to clinical healing was 6.0 weeks. There were no complications of CSWD performed by nurses. The sensitivity for the timely identification of wound deterioration was 100%, specificity = 86.49%, PPV = 68.75% and NPV = 100% with an overall accuracy of 89.58%. The estimated cost savings in this model by having nurses perform CSWD was $223.26 per encounter, which, when extrapolated to national estimates, amounts to $1.56 billion to $2.49 billion in potential annual savings across six to ten-week treatment periods, respectively., Conclusion: CSWD of DFUs by nurses in a vertically integrated multidisciplinary team is a safe, effective, and fiscally responsible clinical practice. This clinical model on a national scale could result in significant healthcare savings. Surgeons and other licensed independent practitioners would have more time for evaluating and treating more complex and operative patients; nurses would be practicing closer to the full extent of their education and training as allowed in most states. Level of Evidence: III ., Competing Interests: Disclosures: The author reports no potential conflicts of interest related to this study., (Copyright © The Iowa Orthopaedic Journal 2020.)

Hypothesis: Locking plates have emerged as the implant of choice for stabilization of proximal humeral fractures. The biomechanical properties of a locked plating system using smooth pegs vs threaded screws for fixation of the humeral head were compared to test the hypothesis that there would be no biomechanical difference between pegs and threaded screws., Materials and Methods: Sixteen pairs of fresh frozen cadaveric humeri were randomized to have a surgical neck gap osteotomy stabilized with a locked plate using threaded screws (n=8) or smooth pegs (n=8). The intact contralateral humerus served as a control. Each specimen was tested with simultaneous cyclic axial compression (40 Nm) and torsion (both +/-2 Nm and +/-5 Nm) for 6000 cycles. All specimens were loaded to failure. Interfragmentary motion and load-displacement curves were analyzed to identify differences between the groups. Our data were then compared to previously published forces across the glenohumeral joint to provide evidence based recommendations for postoperative use of the shoulder., Results: There was a statistically significant difference between test specimens and their paired control (P < .001) in cyclic testing and load to failure. Differences between the smooth pegs and threaded screws were not statistically significant., Discussion: There is no biomechanical difference between locked smooth pegs and locked threaded screws for proximal fragment fixation in an unstable 2-part proximal humeral fracture model., Conclusion: Our study contributes to the published evidence evaluating forces across the glenohumeral joint and suggests that early use of the affected extremity for simple activities of daily living may be safe. Use of the arm for assisted ambulation requiring a crutch, cane, walker, or wheelchair should be determined on a case-by-case basis., (Copyright 2010 Journal of Shoulder and Elbow Surgery Board of Trustees. Published by Mosby, Inc. All rights reserved.)

Background: This study was conducted to evaluate the incidence of transfusion in shoulder arthroplasty, determine clinical factors associated with increased risk for transfusion, and develop an algorithm to assist the surgeon in preoperative planning with regards to blood management., Material and Methods: The study had 2 phases: (1) development of a clinical prediction rule for transfusion using 280 procedures and (2) a validation study of the algorithm applied to 109 new patients. Phase 1 consisted of a retrospective record review of 280 consecutive shoulder arthroplasties to determine risk factors for transfusion. Phase 1 also identified a preoperative hemoglobin level of less than 12.5 g/dL as predictive of the need for blood transfusion. This cutoff was prospectively applied to 109 patients undergoing shoulder arthroplasty in phase 2., Results: The transfusion rate for phase 1 was 19.6%. Preoperative hemoglobin level (P < .001), age (P= .003), and the number of comorbid conditions (P = .005) were statistically significant risk factors. Patients with a preoperative hemoglobin level of less than 12.5 g/dL have a 4-fold increased risk of requiring a blood transfusion. In phase 2, the cutoff of less than 12.5 g/dL yielded a sensitivity of 88%, specificity of 78%, and positive and negative likelihood ratios of 4.0 and 0.15, respectively., Conclusion: Preoperative hemoglobin level, age, and number of comorbid conditions are all predictive of transfusion in shoulder arthroplasty. Tailoring blood ordering based on a preoperative hemoglobin level of 12.5 g/dL is safe and effective., Level of Evidence: Prognostic study, level 2.

Anecdotal case reports describe the occurrence of cystoid macular edema, iritis, herpes simplex keratitis, periocular skin darkening, and headaches in patients treated with prostaglandin analogs for glaucoma. The purpose of this article is to critically analyze these anecdotal case reports in light of a few well-controlled, randomized clinical studies to determine whether conclusions can be made about a causal relationship between the use of prostaglandin analogs and the occurrence of these side effects. None of these putative side effects has been proven to be causally related to latanoprost therapy using valid scientific methodology. These possible side effects occur rarely. Cystoid macular edema, iritis, and herpes simplex keratitis occur in eyes with risk factors. To scientifically establish a causal relationship between drug therapy and rare side effects, repeated rechallenging with masked controls is required. With rare exception, such methodology has not been used with any of these putative side effects. Nevertheless, even without firm establishment of a causal relationship, caution is advised with the use of prostaglandin analogs in eyes with risk factors for cystoid macular edema, iritis, and herpes simplex keratitis until properly designed, large, controlled studies provide more definitive information.

It is now well appreciated that parallel retino-geniculo-cortical pathways exist in the monkey as in the cat, the species in which parallel visual pathways were first and most thoroughly documented. What remains unclear is precisely how many separate pathways pass through the parvo- and magnocellular divisions of the macaque lateral geniculate nucleus (LGN), what relationships-homologous or otherwise-these pathways have to the cat's X, Y, and W pathways, and whether these are affected by visual deprivation. To address these issues of classification and trans-species comparison, we used achromatic stimuli to obtain an extensive set of quantitative measurements of receptive field properties in the parvo- and magnocellular laminae of the LGN of nine macaque monkeys: four normally reared and five monocularly deprived of vision by lid suture near the time of birth. In agreement with previous studies, we find that on average magnocellular neurons differ from parvocellular neurons by having shorter response latencies to optic chiasm stimulation, greater sensitivity to luminance contrast, and better temporal resolution. Magnocellular laminae are also distinguished by containing neurons that summate luminance over their receptive fields nonlinearly (Y cells) and whose temporal response phases decrease with increasing stimulus contrast (indicative of a contrast gain control mechanism). We found little evidence for major differences between magno- and parvocellular neurons on the basis of most spatial parameters except that at any eccentricity, the neurons with the smallest receptive field centers tended to be parvocellular. All parameters were distributed unimodally and continuously through the parvo- and magnocellular populations, giving no indications of subpopulations within each division. Monocular deprivation led to clear anatomical effects: cells in deprived-eye laminae were pale and shrunken compared with those in nondeprived eye laminae, and Cat-301 immunoreactivity in deprived laminae was essentially uniformly abolished. However, deprivation had only subtle effects on the response properties of LGN neurons. Neurons driven by the deprived eye in both magno- and parvocellular laminae had lower nonlinearity indices (i.e., summed signals across their receptive fields more linearly) and were somewhat less responsive. In magnocellular laminae driven by the deprived eye, neuronal response latencies to stimulation of the optic chiasm were slightly shorter than those in the nondeprived laminae, and receptive field surrounds were a bit stronger. No other response parameters were affected by deprivation, and there was no evidence for loss of a specific cell class as in the cat.

Published reports of the occurrence of cystoid macular edema (CME) in eyes being treated with latanoprost have led to concern regarding a possible causal relation between the two. Review of all published cases (28 eyes in 25 patients), plus another case reported here for the first time, indicates that all eyes had independent risk for development of CME, so that definitive conclusions about a causal relation cannot be established. In addition, controlled clinical trials and experimental studies with latanoprost have given no indication that latanoprost causes clinical CME. Pharmacokinetic considerations indicate that the concentration of latanoprost expected in the posterior segment of the eye is too low to have a pharmacologic effect, and latanoprost is not known to exhibit vasoactive or inflammatory properties. Nevertheless, reports of a possible association between CME and latanoprost use must be given serious consideration, and in eyes that are at risk for CME, an increased level of surveillance for its development is recommended.

Purpose: To determine the efficacy and safety of latanoprost treatment for 1 year in glaucoma patients, and to evaluate the effects of switching from timolol to latanoprost therapy., Methods: Latanoprost 0.005% was topically applied once daily without masking for 6 months in 223 patients with elevated intraocular pressure after previous treatment with latanoprost once daily or 0.5% timolol twice daily for 6 months in a multicenter, randomized, double-masked, parallel group study., Results: Compared with baseline values before treatment, a significant (P < .0001) diurnal reduction in intraocular pressure of 6 to 8 mm Hg was maintained with minimal fluctuation for the duration of treatment. When treatment was switched from timolol to latanoprost, intraocular pressure was reduced by 1.5 +/- 0.3 mm Hg (mean +/- SEM; 8% change in intraocular pressure; 31% of the intraocular pressure reduction produced by timolol; P < .001) compared with the change in intraocular pressure in patients remaining on latanoprost therapy. Of the patients initially enrolled, 95% successfully completed treatment. There was a slight overall increase in conjunctival hyperemia in patients who switched from timolol to latanoprost, but no change in those who continued latanoprost. The timolol-induced reduction of resting heart rate returned to baseline levels after switching to latanoprost. Of the 247 patients treated with latanoprost during the masked and/or open-label studies, 12 (5%) demonstrated a definite (n = 4) or possible (n = 8) increase in iris pigmentation., Conclusions: Latanoprost is a well-tolerated ocular hypotensive agent that appears to be more effective than timolol in reducing intraocular pressure. The increase in iris pigmentation appears to be harmless but requires further investigation.

Purpose: To create an experimental glaucoma monkey model using high-power diode laser photocoagulation of the trabecular meshwork, and to compare this with the experimental glaucoma monkey model induced by argon laser photocoagulation of the trabecular meshwork., Methods: One eye each of eight adult cynomolgus monkeys underwent repeated application of diode laser photocoagulation of the trabecular meshwork until sustained intraocular pressure (IOP) elevation was achieved. 50 to 120 spots were applied to midtrabecular meshwork for 360 degrees; spot size, 75 microns; power, 1.2 W; duration, 0.5 seconds. Intraocular pressure, tonographic outflow facility, and ophthalmoscopically and photographically documented optic nerve head evaluations were carried out before and after treatment. Data were compared retrospectively with similar data from an experimental glaucoma monkey model after argon laser photocoagulation of the trabecular meshwork (n = 10)., Results: The average number of laser treatments to achieve stable IOP elevation was 3.0 with both diode and argon laser trabecular treatments (p > 0.99). On week 4 after initial pressure elevation, peak IOP was greater--(p < 0.05) 43.0 mmHg +/- 2.4 mmHg (mean +/- SEM) and 37.4 mmHg +/- 1.3 mmHg--in the diode laser-induced than in the argon laser-induced glaucomatous eyes, respectively. Outflow facility (microliter/min/mmHg) was reduced (p < 0.001) in both diode (0.09 +/- 0.01 microliter/min/mmHg) and argon (0.10 +/- 0.01 microliter/min/mmHg) laser-induced glaucomatous eyes compared with untreated fellow eyes. Both the diode and argon laser techniques produced the earliest signs of optic nerve head excavation within about one month of IOP elevation., Conclusions: Repeat diode laser photocoagulation of the trabecular meshwork produced higher (p < 0.05) IOP elevation than argon laser photocoagulation of the trabecular meshwork in this study. No significant differences in outflow facility and optic nerve head change were observed between these two laser techniques. The experimental glaucoma monkey model can be created with either the diode or argon laser photocoagulation of the trabecular meshwork.

Objective: To explore the possibility that the excitatory amino acid glutamate might be associated with the disease process of glaucoma, which is characterized by the death of retinal ganglion cell neurons and subsequent visual dysfunction., Methods: Amino acid analyses were performed on vitreous specimens that were obtained from patients who were undergoing cataract extraction. Samples were collected prospectively from those patients who sustained inadvertent rupture of the posterior capsule between 1988 and 1993. An additional set of specimens, obtained from both eyes of monkeys, was analyzed; in these monkeys, glaucoma had been experimentally induced in one eye only., Results: A twofold elevation in the level of glutamate was detected in the vitreous body of the group of patients with glaucoma when compared with that in a control population of patients with cataracts only. An even greater elevation of the glutamate level was found in the vitreous body of glaucomatous eyes of monkeys when compared with that in control eyes. No statistical differences were detected among other amino acid levels from the vitreous body of glaucomatous and nonglaucomatous eyes in humans or monkeys., Conclusions: The excitatory amino acid glutamate is found in the vitreous body of glaucomatous eyes at concentrations that are potentially toxic to retinal ganglion cells. The increased level of this known neurotoxin is consistent with an "excitotoxic" mechanism for the retinal ganglion cell and optic nerve damage in glaucoma. Therapies to protect neurons against glutamate toxic effects may prove to be useful in the management of this blinding disease.

Purpose: We used a modified technique to construct the trabeculectomy flap., Methods: The technique involved the creation of a scleral tunnel as is used in phacoemulsification surgery for cataract., Results: We have used this technique in our most recent 90 cases. We believe it is an easier technique to perform than conventional flap dissection, and that it yields improved flap construction., Conclusions: The scleral tunnel flap technique offers a number of advantages over standard flap construction in trabeculectomy surgery.

The vulnerability of subpopulations of retinal neurons delineated by their content of cytoskeletal or calcium-binding proteins was evaluated in the retinas of cynomolgus monkeys in which glaucoma was produced with an argon laser. We quantitatively compared the number of neurons containing either neurofilament (NF) protein, parvalbumin, calbindin or calretinin immunoreactivity in central and peripheral portions of the nasal and temporal quadrants of the retina from glaucomatous and fellow non-glaucomatous eyes. There was no significant difference between the proportion of amacrine, horizontal and bipolar cells labeled with antibodies to the calcium-binding proteins comparing the two eyes. NF triplet immunoreactivity was present in a subpopulation of retinal ganglion cells, many of which, but not all, likely correspond to large ganglion cells that subserve the magnocellular visual pathway. Loss of NF protein-containing retinal ganglion cells was widespread throughout the central (59-77% loss) and peripheral (96-97%) nasal and temporal quadrants and was associated with the loss of NF-immunoreactive optic nerve fibers in the glaucomatous eyes. Comparison of counts of NF-immunoreactive neurons with total cell loss evaluated by Nissl staining indicated that NF protein-immunoreactive cells represent a large proportion of the cells that degenerate in the glaucomatous eyes, particularly in the peripheral regions of the retina. Such data may be useful in determining the cellular basis for sensitivity to this pathologic process and may also be helpful in the design of diagnostic tests that may be sensitive to the loss of the subset of NF-immunoreactive ganglion cells.

Aims: A study was conducted to estimate the frequency of contamination of topical antiglaucoma medications used by asymptomatic patients., Methods: The drops and the bottle tips of 194 in use topical medications and the conjunctiva from 109 treated glaucoma patients were cultured., Results: Bacteria were recovered from 55 (28%) medications. The bottle tip was more frequently contaminated than the drops (p = 0.008). Gram positive organisms were cultured from 50 (91%) of 55 contaminated medications. Thirteen patients (12%) had the same microorganism recovered from the conjunctiva and from the contaminated medication. The frequency of contamination of medications increased with increasing duration of use. Bacterial contamination occurred in 19% of eyedrops less than 8 weeks old in contrast with 40% of bottles used for more than 8 weeks., Conclusion: Our data suggest that ocular medications to treat glaucoma frequently become contaminated with bacteria and that contamination is related to duration of use. We therefore recommend that opened topical antiglaucoma eyedrops should be replaced on a regular basis.

Contemporary concepts of open angle glaucoma suggest that the current emphasis on reduction of elevated intraocular pressure could be augmented by other therapeutic approaches. In this article, we describe significant recent developments in the molecular and cellular biology and neuropharmacology of nerve damage that are likely, in coming years, to suggest new therapeutic approaches to the management of glaucoma. These developments may lead to the achievement of pharmacologic protection of the optic nerve from damage or possibly promotion of reversal of damage. We review selected studies of excitotoxins and N-methyl-D-aspartate receptor antagonists, Ca(2+)-induced damage and calcium channel blockers, the intracellular messenger nitric oxide and its perturbation, free-radical damage and scavengers, nerve regeneration, and growth factors. Several basic research questions are posed, answers to which may transform our concepts of glaucoma therapy.

In a randomized, double-masked, parallel study, one drop of 0.003% (1 microgram; n = 9) or 0.01% (3 micrograms; n = 10) PhXA34, a new phenyl-substituted prostaglandin F2 alpha analogue (13,14-dihydro-15[R,S]-17-phenyl-18,19,20-trinor-prostaglandin F2 alpha-1-isopropyl ester), or its vehicle (n = 10) was applied topically twice daily for 6 days to one eye in each of 29 patients with ocular hypertension. Compared with either baseline, contralateral, or vehicle control values, PhXA34 caused a significant (P < .001) dose-dependent reduction of intraocular pressure. The reduction lasted at least 12 hours after each drop and 24 to 48 hours after the last drop, with a significant (P < .0001) mean +/- SEM reduction of as much as 10 +/- 1 mm Hg (40%). Conjunctival hyperemia was not produced by 0.003% PhXA34, but was noted in some eyes treated with 0.01% PhXA34, and after repeated tonometry with either concentration. The prostaglandin analogue did not produce clinically obvious miosis, anterior chamber flare or cellular response, or any subjective adverse effects. PhXA34 is a potent, effective, and well-tolerated ocular hypotensive agent based on our results in this small, short-term study. Its potential as a new drug for glaucoma therapy warrants further investigation in long-term, larger studies.

1. We consider the consequences of the orientation selectivity shown by most cortical neurons for the nature of the signals they can convey about the direction of stimulus movement. On theoretical grounds we distinguish component direction selectivity, in which cells are selective for the direction of movement of oriented components of a complex stimulus, from pattern direction selectivity, or selectivity for the overall direction of movement of a pattern irrespective of the directions of its components. We employed a novel test using grating and plaid targets to distinguish these forms of direction selectivity. 2. We studied the responses of 280 cells from the striate cortex and 107 cells from the lateral suprasylvian cortex (LS) to single sinusoidal gratings to determine their orientation preference and directional selectivity. We tested 73 of these with sinusoidal plaids, composed of two sinusoidal gratings at different orientations, to study the organization of the directional mechanisms within the receptive field. 3. When tested with single gratings, the directional tuning of 277 oriented cells in area 17 had a mean half width of 20.6 degrees, a mode near 13 degrees, and a range of 3.8-58 degrees. Simple cells were slightly more narrowly tuned than complex cells. The selectivity of LS neurons for the direction of moving gratings is not markedly different from that of neurons in area 17. The mean direction half width was 20.7 degrees. 4. We evaluated the directional selectivity of these neurons by comparing responses to stimuli moved in the optimal direction with those elicited by a stimulus moving in the opposite direction. In area 17 about two-thirds of the neurons responded less than half as well to the non-preferred direction as to the preferred direction; two-fifths of the units responded less than one-fifth as well. Complex cells showed a somewhat greater tendency to directional bias than simple cells. LS neurons tended to have stronger directional asymmetries in their response to moving gratings: 83% of LS neurons showed a significant directional asymmetry. 5. Neurons in both areas responded independently to each component of the plaid. Thus cells giving single-lobed directional-tuning curves to gratings showed bilobed plaid tuning curves, with each lobe corresponding to movement in an effective direction by one of the two component gratings within the plaid. The two best directions for the plaids were those at which one or other single grating would have produced an optimal response when presented alone.(ABSTRACT TRUNCATED AT 400 WORDS)

Corrugated disparity gratings mounted on depth pedestals were portrayed with random-dot stereograms in order to measure the cyclopean disparity modulation transfer function at various offsets from fixation. We found changes in both sensitivity as well as shape as the magnitude of the pedestal varied. Threshold disparity modulation amplitude curves, plotted as a function of corrugation frequency, became narrower and shifted toward lower frequencies as pedestal size increased. There were stable asymmetries between sensitivities to crossed and uncrossed pedestals; these could be accounted for by assuming each observer to have a constant fixation disparity on the order of 5' of arc.

We have examined two models for the preference displayed by cortical simple cells for elongated stimuli having a particular orientation. Both assume that geniculate afferents with aligned receptive fields pool to form the receptive field of the cortical unit. The first model [Marr and Hildreth, Proc. R. Soc. Lond. Ser. B 200, 269-294 (1980)], includes AND gating along the length axis so that a simple cell does not fire unless a critical number of its afferents with adjacent receptive fields are firing. The second model assumes that geniculate input is simply summed over subunits and then passed through a firing threshold. Both models account for the unresponsiveness of simple cells to spots of light, but the AND model predicts a discontinuous length threshold, while the summation model predicts that length and contrast should be interchangeable in the determination of the response threshold. Experiments in which length and contrast were systematically varied support the summation model, and extend the notion of linear spatial summation to the length axis in simple cells.

We reared cats in an environment illuminated stroboscopically at 8 Hz, and studied their ability to detect and discriminate the direction of motion of sinusoidal gratings. Normal cats, like humans, could discriminate the direction of a grating's motion at contrasts that are just barely visible. Strobe-reared cats could detect the grating at contrasts similar to those required by normal cats, but required contrasts that were about 10 times threshold to identify the direction of motion. We subsequently studied the activity of single units in the striate cortex in these cats, and found that directional motion selectivity--normally a prominent feature of striate cortical neurons--was almost absent; other cortical receptive field properties were roughly normal. These results suggest that directionally selective neurons are involved in visual discriminations based on the direction of motion.