Ankur Gandhi

Complications of Ankle Fracture in Patients With Diabetes

Abstract Ankle fractures in patients with diabetes mellitus have long been recognized as a challenge to practicing clinicians. Complications of impaired wound healing, infection, malunion, delayed union, nonunion, and Charcot arthropathy are prevalent in this patient population. Controversy exists as to whether diabetic ankle fractures are best treated noninvasively or by open reduction and internal fixation. Patients with diabetes are at significant risk for soft‐tissue complications. In addition, diabetic ankle fractures heal, but significant delays in bone healing exist. Also, Charcot ankle arthropathy occurs more commonly in patients who were initially undiagnosed and had a delay in immobilization and in patients treated nonsurgically for displaced ankle fractures. Several techniques have been described to minimize complications associated with diabetic ankle fractures (eg, rigid external fixation, use of Kirschner wires or Steinmann pins to increase rigidity). Regardless of the specifics of treatment, adherence to the basic principles of preoperative planning, meticulous soft‐tissue management, and attention to stable, rigid fixation with prolonged, protected immobilization are paramount in minimizing problems and yielding good functional outcomes.

The effects of low-intensity pulsed ultrasound upon diabetic fracture healing

In the United States, over 17 million people are diagnosed with type 1 diabetes mellitus (DM) with its inherent morbidity of delayed bone healing and nonunion. Recent studies demonstrate the utility of pulsed low‐intensity ultrasound (LIPUS) to facilitate fracture healing. The current study evaluated the effects of daily application of LIPUS on mid‐diaphyseal femoral fracture growth factor expression, cartilage formation, and neovascularization in DM and non‐DM BB Wistar rats. Polymerase chain reaction (PCR) and ELISA assays were used to measure and quantify growth factor expression. Histomorphometry assessed cartilage formation while immunohistochemical staining for PECAM evaluated neovascularization at the fracture site. In accordance with previous studies, LIPUS was shown to increase growth factor expression and cartilage formation. Our study also demonstrated an increase in fracture callus neovascularization with the addition of LIPUS. The DM group showed impaired growth factor expression, cartilage formation, and neovascularization. However, the addition of LIPUS significantly increased all parameters so that the DM group resembled that of the non‐DM group. These findings suggest a potential role of LIPUS as an adjunct for DM fracture treatment.

Electrical Bone Stimulation Devices in Foot and Ankle Surgery: Types of Devices, Scientific Basis, and Clinical Indications for Their Use

Over the last few decades, increasing attention has been focused on the use of electrostimulation to aid osseous healing. Since the pioneering work of Yasuda in the 1950s focusing on the concept of piezoelectric fields associated with bone, intense scientific research has analyzed the application of electrostimulation technology. “Piezoelectricity” is the ability of certain crystals to produce a voltage when subjected to mechanical stress. The word is derived from the Greek “piezein,” which means to squeeze or press. In a piezoelectric crystal, the positive and negative electrical charges are separated, but symmetrically distributed, so that the crystal overall is electrically neutral. When a stress is applied, this symmetry is disturbed, and the charge asymmetry generates a voltage. Bone, which is rich in calcium phosphate crystals also produces similar potentials if stressed. The compression side has a negative potential, while the tension side has a positive potential. Another important form of electric potential associated with bone, especially traumatized bone, is transmembrane (bioelectric) potentials, which are generated by cellular metabolism and depend on cell viability. Areas of greatest cellular activity demonstrate the greatest negative potential. The phenomena of piezoelectric and bioelectric potentials are important in modifying a variety of processes in both the early callus and later remodeling phases of fracture healing. Hence, the application of exogenous electrical potentials either as an adjunct to accelerate osseous healing or as an alternative to operative intervention (for nonunion) may facilitate bony union by positively influencing the fracture-healing cascade.

Bone Allograft Safety and Performance

Bone allograft transplantation is a common practice; in the United States 650,000 procedures were performed in 1999, a 186% increase from 1990 [3]. This increase can be attributed to morbidities associated with bone autografts [6, 18, 30, 35, 59], the increased availability of bone allografts, and the expansion of these applications [9, 16, 21, 22, 29, 31, 42, 66]. A variety of musculoskeletal allografts are available for different reconstructive applications. Bone allograft is an alternative to autograft because it has osteoconductive properties, acts as a scaffold for bone growth, and induces bone formation by providing osteogenic factors, in addition to mesenchymal precursor cells, osteoblasts, and osteocytes. Although these properties are advantageous, the potential for the transmission of infectious diseases remains a great concern [1, 2, 4, 10, 12, 24, 26, 27, 32, 38, 49, 53].

Interaction between the opposing functional effects of cyclic AMP and cyclic GMP in hypertrophic cardiac myocytes.

Abstract We tested the hypothesis that in isolated cardiac myocytes, the negative functional effects of cyclic GMP would be blunted when the level of cyclic AMP was increased and that this interaction would be altered in renal hypertensive (One-Kidney-One-Clip, 1K1C) cardiac hypertrophic rabbits. Using isolated control and 1K1C ventricular myocytes, cyclic AMP and cell shortening (%) data were collected: 1) at baseline, 2) after the addition of 8-Br-cGMP 10−7, −6, −5 M, and 3) after forskolin (10−6 M), and adenylate cyclase activator, followed by 8-Br-cGMP 10−7, −6,−5 M. Basal levels of cyclic AMP were similar in control vs. 1K1C myocytes (10.2 ± 1.6 vs. 11.3 ± 2.6 pmol/105 myocytes). We found that 8-Br-cGMP decreased the percent shortening in a dose related manner in both control myocytes (5.1 ± 0.6 to 3.2 ± 0.4%) and hypertrophic myocytes (5.2 ± 0.4 to 3.6 ± 0.5). The level of cyclic AMP significantly increased after the addition of 8-Br-cGMP in control myocytes (14.1 ± 2.1), but not in 1K1C myocytes. Forskolin increased the percent shortening in the control myocytes (3.8 ± 0.1 to 4.8 ± 0.4), but no significant increase was noted in the hypertrophic myocytes (3.6 ± 0.3 to 3.7 ± 0.3). The level of cyclic AMP significantly increased after the addition of forskolin in both control (13.9 ± 2.0), and 1K1C cells (14.6 ± 3.8). Forskolin attenuated the negative functional effects of 8-Br-cGMP in the control (4.8 ± 0.4 to 3.2 ± 0.1) and 1K1C myocytes (3.7 ± 0.3 to 2.7 ± 0.3). The adition of 8-Br-cGMP did not affect the level of cyclic AMP after forskolin in either control (13.9 ± 2.0 to 14.8 ± 2.5) or 1K1C myocytes (14.6 ± 3.8 to 13.8 ± 1.9). These data indicated that in hypertrophic cardiac myocytes the negative functional effects of 8-Br-cGMP were similar to control, but the positive functional effects of cyclic AMP were blunted. There was an increase in cyclic AMP levels after addition of 8-Br-cGMP in control but not 1K1C cells. We conclude that in control and hypertrophic myocytes, the effects of cyclic GMP were blunted after forskolin, but this did not seem to be related to cyclic AMP phosphodiesterase activity.

Negative effect of nitric oxide onshorteningfrequency relationship in cardiac myocytes isdiminished after simulated ischemia-reperfusion

Abstract.Increasing stimulation rate increases function in cardiac myocytes and nitric oxide and cyclic GMP inhibit this effect. We tested the hypothesis that myocyte stunning would blunt both the effects of increases in rate and of nitric oxide and cyclic GMP. Ventricular myocytes from 11 rabbits were used to determine maximum rate of shortening (Rmax, µm/s) and %shortening during control and after simulated ischemia [15 min 95% N2- 5% CO2] and reperfusion [reoxygenation]. Measurements were obtained at 1–4 Hz with vehicle, 1H[1,2,4]oxadiazolo[4,3,alpha] quinoxaline-1-one (ODQ) 10–6 M, soluble guanylyl cyclase inhibitor, or NG-nitro-L-arginine methyl ester, nitric oxide synthase inhibitor (L-NAME) 10–5 M. In control, increases in rate increased Rmax from 69 ± 3 to 254±12 and %shortening from 5.3 ± 0.3 to 8.7 ± 0.5. Both ODQ and L-NAME shifted values higher. With stunning, the effects of pacing on Rmax and %shortening were blunted and ODQ and L-NAME failed to alter these values. Cyclic GMP was 322±37 pmol/105 myocytes at baseline and these values were lowered by ODQ (244 ± 31) and LNAME (207 ± 23), and similar changes were observed in stunned myocytes. Increasing frequency increased function, and reducing nitric oxide/cyclic GMP enhanced this relationship. The effect of nitric oxide was diminished by stunning, but this was not related to altered cyclic GMP levels. This suggested changes in effects of cyclic GMP downstream to its production during myocardial stunning.