Limb salvage for soft-tissue malignancies of the foot: an evaluation of free-tissue transfer.

Free flaps may safely allow meaningful ambulation, durable limb preservation, and better quality of life in patients undergoing resections of soft-tissue cancers of the foot. To prove this, the records of a series of patients at The University of Texas M. D. Anderson Cancer Center (n = 67) who underwent limb salvage following tumor-related resection (n = 71 procedures) from 1989 to 1999 were retrospectively reviewed. Eighteen patients who were not candidates for local flaps or skin grafts received a total of 20 free flaps to preserve their limbs. Most defects (mean size, 78 cm2; range, 20 to 150 cm2) were on a weight-bearing surface of the foot (nine on a weight-bearing heel, three on a plantar foot); the remainder were on a non-weight-bearing surface (six on dorsum, two on a non-weight-bearing heel). Melanoma was diagnosed in nine cases (50 percent); soft-tissue sarcoma, in seven (39 percent); and squamous cell carcinoma, in two (11 percent). Fasciocutaneous and skin-grafted muscle flaps were used on both weight-bearing and non-weight-bearing surfaces. Free-tissue transfer was successful in 17 of 20 cases (85 percent); the three flap losses occurred in two patients. Minor complications (i.e., small hematoma, partial skin graft loss, and delayed wound healing) occurred in five patients. In all cases of successful free-tissue transfer, patients began partial weight bearing at a mean of 7.4 weeks (range, 2 to 12 weeks), and all ultimately achieved full weight bearing. Sixty-seven percent still required special footwear. In one patient, an ulceration on the weight-bearing portion of the flap resolved after a footwear adjustment. Only one patient was lost to follow-up (mean, 23 months). In the 17 remaining patients, limb salvage succeeded in 15 (88 percent). Of these, nine (60 percent) were alive without evidence of disease, three (20 percent) were alive with disease, and three (20 percent) had died of disease. Local recurrence developed in two patients but was successfully treated by excision and closure. No late amputations were required for local control. Thus, it seems that free flaps help facilitate limb salvage and that they may preserve meaningful limb function in patients who undergo resection of soft-tissue malignancies of the foot.     

Training penguins to interact with enrichment devices for lasting effects

The modern zoo has brought about two major advances in the behavioral welfare of their exhibited animals: (a) The use of environmental enrichment to promote naturalistic behaviors and (b) the use of training to improve voluntary husbandry care. Whereas training itself has been talked about as an effective enrichment strategy, little has been done to combine training procedures with enrichment. Typically, enrichment is treated as a trial and error process, where potential enrichment items or procedures are cycled through until successful enrichment is found. The use of shaping or other training techniques has seldom been documented to increase engagement with possible enrichment items or procedures. The following study examined the possibility of combining training and enrichment to produce continued interactions with enrichment devices. Two species of penguin, Magellanic and southern rockhopper penguins, were studied. Two measures were taken: Time spent swimming and contact with enrichment devices. The enrichment devices could be manipulated by placing fish within and hanging out of each device. During baseline sessions, no hits to either device were observed. During training sessions, several hits were recorded when fish were in the devices and overall swimming time increased during these conditions. When baseline was reintroduced without fish in the devices, contact with the enrichment devices rapidly declined and swimming time for the rockhopper penguins decreased. When the devices were reintroduced with fish but without training, the greatest number of enrichment device contacts and the highest percentage of time spent swimming were observed for the rockhopper penguins.     

Ethics of the heart: ethical and policy challenges in the treatment of advanced heart failure

Heart failure is a major cause of morbidity and mortality in the United States and worldwide, accounting for immense health-care costs. Advanced therapies such as transplantation, ventricular assist devices, and implantable cardioverter defibrillators have had great success in significantly improving life expectancy and morbidity, however these advances have contributed substantially to the economic burden associated with this epidemic. Concomitantly, the accessibility of these advanced therapies is limited, due to a finite number of available organs for heart transplantation and, in the future, the economic costs associated with both transplant and device therapy. This article discusses ethical and policy challenges in the treatment of advanced heart failure, including decisions regarding procurement of hearts for transplant and allocation to recipients; and the complex issues surrounding the use of implantable cardioverter defibrillators and ventricular assist devices, including quality of life, advanced directive planning in the context of these devices, and resource utilization. Based on these challenges, we recommend that a discussion of these complex matters be incorporated into cardiovascular training programs.     

Review: Artificial liver support systems

Despite recent advances in medical therapy, patients with fulminant hepatic failure (FHF) have a mortality rate approaching 90%. Many patients die because of failure to arrest the progression of cerebral edema. Liver transplantation has improved survival to 65% to 75%. However, there is a shortage of donors and approximately one half of the patients with FHF will die while awaiting liver transplantation. There is thus a need to develop an extracorporeal liver assist system to help keep these patients alive and neurologically intact until either an organ becomes available for transplantation or the native liver recovers from injury. Such a system could also be used during the period of functional recovery from massive liver resection or to assist patients with decompensated chronic liver disease. Over the years, various methods utilizing charcoal and resin hemoperfusion, dialysis, plasma exchange, and other methods of blood detoxification have been developed and tested, but none have gained wide acceptance. This was due to: (i) incomplete understanding of the pathophysiology of liver failure; (ii) lack of accurate methods of assessment, quantitation, and stratification of the degree of liver dysfunction; and (iii) inadequate numbers of prospective controlled clinical trials examining the effects of specific therapeutic modalities. Liver support systems utilizing liver tissue preparations were developed in the 1950s, but it was not until recently that advances in hepatocyte isolation and culture, better understanding of hepatocyte-matrix interactions, and improved hollow-fiber technology have resulted in the development of a new generation of liver assist devices. Some of these devices are currently being tested in the clinical setting. In a preliminary clinical study, we have used a porcine hepatocyte-based liver support system to treat patients with acute liver failure as well as patients with acute exacerbation of chronic liver disease. Patients in the first group, who were candidates for transplantation, were successfully bridged to a transplant with excellent survival. No obvious benefit from bioartifical liver treatments was seen in the second group. It is possible that, in this group, patients will have to be treated earlier and for longer periods of time. Prospective controlled trials will be initiated as soon as the current phase I study is concluded to determine the efficacy of this system in both patients populations. (c) 1996 John Wiley & Sons, Inc.     

Partial regeneration of the above-elbow amputated rat forelimb. II. Electrical and mechanical facilitation.

This investigation was undertaken to examine the observations of Becker ('72) pertaining to the electrical facilitation of partial limb regenerative responses by means of Ag-Pt wire couples applied to the limb stumps of young, forelimb-amputated white rats. Additionally, in order to examine the possible role of mechanical effects of such device implantations, we have employed uncoupled devices delivering no current or potential difference. In the present experiments, in response to coupled device implantation, cartilage and bone were actively formed in the vicinity of the Pt electrode tip. These tissues contributed to the lengthwise extension of the limb and to the partial restoration of the distal humeral extremity. In limbs bearing the uncoupled electrical devices, qualitatively similar responses were noted, but osteogenesis was diminished in extent compared to that seen in limbs bearing the active or coupled devices. It is therefore necessary to consider the role of mechanical factors in the elicitation of the observed regenerative responses. Myogenesis was enhanced in electrically stimulated limbs, but not in those rats bearing uncoupled devices.     

Free microvascular muscle flaps with skin graft reconstruction of extensive defects of the foot: a clinical and gait analysis study

Over the past 4 years at the Massachusetts General Hospital 18 patients have been treated for extensive defects (mean size 130 cm2) of the foot at or below the medial and lateral malleoli. These patients have been treated with free muscle flaps covered with thick split-thickness skin grafts. Full muscle flap survival has been seen in each patient, and all patients are currently ambulatory. A subgroup of nine patients are weight-bearing directly upon their skin grafts covering transferred muscle. All patients are walking without chronic breakdown over a mean follow-up of over 19 months with the exception of a single patient who has had breakdown in a region of redundant improperly tailored muscle flap. None of the skin grafted muscles has significant cutaneous sensibility. Detailed gait analysis of these patients has confirmed the weight-bearing capabilities of free muscle flaps with skin grafts and has proven to be an excellent method of foot reconstruction evaluation. It would appear from this study that cutaneous sensibility may not be necessary for successful reconstruction of the weight-bearing surface of the foot. This method of reconstruction should be considered when local tissues are not suitable for plantar foot reconstruction.     

Biomimetic Leukocyte Adhesion： A Review of Microfluidic and Computational Approaches and Applications

Leukocyte rolling and adhesion are complex physiological processes that have received a great deal of attention over the past decade. Significant increases in the knowledge base related to how leukocytes adhere in shear flows have occurred as a result of the development of novel experimental and computational techniques. Micro- and nano-fabrication techniques have enabled the development of novel flow devices for studying leukocyte adhesion in simple and complex geometries. Improvements in computer technology have enabled simulations of complex flow processes to be developed. As a result of these advances in knowledge related to leukocyte adhesion, numerous novel devices have been developed that mimic the leukocyte rolling and adhesion process. Examples of these devices include cell separation and enrichment devices and targeted ultrasound contrast agents. Future advances related to leukocyte rolling and adhesion processes hold great promise for advancing our knowledge of disease processes as well as development of novel therapeutic devices.     

Balance Asymmetry in Parkinson’s Disease and Its Contribution to Freezing of Gait

Balance control (the ability to maintain an upright posture) is asymmetrically controlled in a proportion of patients with Parkinson’s disease. Gait asymmetries have been linked to the pathophysiology of freezing of gait. We speculate that asymmetries in balance could contribute to freezing by a) hampering the unloading of the stepping leg and/or b) leading to a preferred stance leg during gait, which then results in asymmetric gait. To investigate this, we examined the relationship between balance control and weight-bearing asymmetries and freezing. We included 20 human patients with Parkinson (tested OFF medication; nine freezers) and nine healthy controls. Balance was perturbed in the sagittal plane, using continuous multi-sine perturbations, applied by a motion platform and by a force at the sacrum. Applying closed-loop system identification techniques, relating the body sway angle to the joint torques of each leg separately, determined the relative contribution of each ankle and hip joint to the total amount of joint torque. We also calculated weight-bearing asymmetries. We determined the 99-percent confidence interval of weight-bearing and balance-control asymmetry using the responses of the healthy controls. Freezers did not have larger asymmetries in weight bearing (p = 0.85) nor more asymmetrical balance control compared to non-freezers (p = 0.25). The healthy linear one-to-one relationship between weight bearing and balance control was significantly different for freezers and non-freezers (p = 0.01). Specifically, non-freezers had a significant relationship between weight bearing and balance control (p = 0.02), whereas this relation was not significant for freezers (p = 0.15). Balance control is asymmetrical in most patients (about 75 percent) with Parkinson’s disease, but this asymmetry is not related to freezing. The relationship between weight bearing and balance control seems to be less pronounced in freezers, compared to healthy controls and non-freezers. However, this relationship should be investigated further in larger groups of patients.     

Implantable diagnostic and therapeutic devices in children

Many advances have been made in the use of implantable diagnostic and therapeutic devices in adults. In children the indications for and diagnostic and therapeutic value of these devices still have to be determined.Our aim is to provide an overview of the clinical use of diagnostic and therapeutic devices in children. The role of implantable loop recorders (ILR), the feasibility and safety of transvenous pacing in neonates, the value of permanent pacing in children with recurrent syncope or reflex anoxic seizures and the role of implantable cardioverter defibrillator devices are highlighted with relevant case histories.     

Treatment of late ulceration in free muscle flaps to the foot

One of the preferred methods for the repair of large defects of the foot has been the use of free muscle flaps covered with skin grafts. Although this method has served well, some patients will experience ulceration in the weight-bearing surface. Three cases are reported in which small ulcerations developed in the heel after reconstruction of traumatic defects with muscle free flaps. All three patients were treated with a neurovascular island flap from the side of the great toe. All three patients are active young males, and all three patients have subsequently maintained intact skin for an average of 6.8 years (range, 5.1 to 9.1 years).     

Microreactors for peptide synthesis: looking through the eyes of twenty first century !!!

The twenty first century has witnessed several advances in synthetic chemistry, among them microreactors. It is expected that these devices will have a considerable impact on synthetic organic chemistry since they offer a wide range of applications in various fields. Perhaps the synthesis of peptides deserves mention in this regard as these molecules are emerging as therapeutics and offer several advantages over the so-called small molecules. This minireview does not aim to address microreactors in detail, but explains various peptide synthesis methods that involve microfluidic techniques, highlighting the need for further improvement and expansion of microdevices/microreactors.     

Highly Efficient Materials Assembly Via Electrophoretic Deposition for Electrochemical Energy Conversion and Storage Devices

Featuring pronounced controllability, versatility, and scalability, electrophoretic deposition (EPD) has been proposed as an efficient method for film assembly and electrode/solid electrolyte fabrication in various energy storage/conversion devices including rechargeable batteries, supercapacitors, and fuel cells. High‐quality electrodes and solid electrolytes have been prepared through EPD and exhibit advantageous performances in comparison with those realized with traditional methods. Recent advances in the application of EPD materials in electrochemical energy storage and conversion devices are summarized. In particular, the parameters that influence the efficiency of an EPD process from colloidal preparation to deposition are evaluated with the aim to provide insightful guidance for realizing high‐performance electrochemical energy conversion materials and devices.     

Disuse in adult male rats attenuates the bone anabolic response to a therapeutic dose of parathyroid hormone.

Intermittent treatment with parathyroid hormone (PTH) increases bone formation and prevents bone loss in hindlimb-unloaded (HLU) rats. However, the mechanisms of action of PTH are incompletely known. To explore possible interactions between weight bearing and PTH, we treated 6-mo-old weight-bearing and HLU rats with a human therapeutic dose (1 microg.kg(-1).day(-1)) of human PTH(1-34) (hPTH). Cortical and cancellous bone formation was measured in tibia at the diaphysis proximal to the tibia-fibula synostosis and at the proximal metaphysis, respectively. Two weeks of hindlimb unloading resulted in a dramatic decrease in the rate of bone formation at both skeletal sites, which was prevented by PTH treatment at the cancellous site only. In contrast, PTH treatment increased cortical as well as cancellous bone formation in weight-bearing rats. Two-way ANOVA revealed that hPTH and HLU had independent and opposite effects on all histomorphometric indexes of bone formation [mineral apposition rate (MAR), double-labeled perimeter (dLPm), and bone formation rate (BFR)] at both skeletal sites. The bone anabolic effects of weight bearing and hPTH on dLPm and BFR at the cortical site were additive, as were the effects on MAR at the cancellous site. In contrast, weight bearing and hPTH resulted in synergistic increases in cortical bone MAR and cancellous bone dLPm and BFR. We conclude that weight bearing and PTH act cooperatively to increase bone formation by resulting in site-specific additive and synergistic increases in indexes of osteoblast number and activity, suggesting that weight-bearing exercise targeted to osteopenic skeletal sites may improve the efficacy of PTH therapy for osteoporosis.     

Third-generation continuous flow left ventricular assist devices

Tremendous advances have been made in the treatment of end-stage heart failure patients with left ventricular assist devices (LVADs). An important factor playing a role in the improved clinical outcomes is the development of continuous flow, rotary LVADs. New technology using magnetic levitation and hydrodynamic suspension to eliminate contact bearings offers the potential of more durable and efficacious mechanical circulatory blood pumps. Clinical trials evaluating these novel "third-generation" LVADs are in progress.     

Characteristic Features of Disorders of the Upright Posture in Patients with Poststroke Hemipareses

Characteristic features of upright posture maintenance and mechanisms of postural disorders in poststroke hemiparetic patients were studied using a bilateral force platform. The following features of postural disorders were revealed in the patients tested: an increase in the velocity and amplitude of the center-of-pressure (CP) sway as compared to in healthy subjects, an absolute decrease in the half-cycles of the CP sway, asymmetry of weight bearing by both feet, and a shift of the center of pressure of an affected foot towards the toe. The disturbance of stability of the vertical posture in such patients is to a greater extent associated with weight-bearing asymmetry. It was shown that the character of the CP sway is mainly determined by a disorder of the sensory motor control, whereas damage to the efferent pathways is responsible for the postural asymmetry. Increase in the muscle tone restricts the sway amplitude. Thus, several forms of postural instability are characteristic of hemiparetic patients. Predominantly sensory, motor, or tonic disorders are responsible for these disturbances of stability.     

Influence of weight bearing on the adaptations of rat plantaris to ablation of its synergists

The present study was designed to determine the contribution of weight bearing to the adaptations of the plantaris (PL) to synergist removal. PL from female rats were exposed to 28 days of a simultaneous condition of synergist ablation and hindlimb suspension. At 28 days, contractile responses and morphological measures were obtained and compared with muscles that either had synergists intact or were weight bearing or a combination of both. Synergist ablation prolonged PL maximum isometric twitch tension (Pt), time to peak tension (12%), and one-half relaxation time (12%); increased Pt (26%), maximum isometric tetanic tension (Po, 44%), fatigue resistance (FI, 42%), and fast fiber cross-sectional area (FT CSA, 20%); and decreased Pt/Po (13%) over nonablation counterparts. Suspension decreased PL Pt (26%), Po (26%), rest length (16%), FT CSA (31%), and slow-twitch fiber (ST) number (24%) but increased FI (75%) over weight-bearing counterparts. PL from weight-bearing animals were heavier than from suspended animals, and the extent of this response was greatest after synergist removal. Whole muscle and ST CSA and ST area contribution were greater only in weight-bearing synergist ablation muscles. Daily weight bearing (4 h) in synergist ablation hindlimb suspension groups caused PL weights and ST expressions to be halfway between 24-h suspension and 24-h weight-bearing groups. Our results suggest that weight bearing is not essential to the induction of several adaptations associated with synergist ablation but is required to cause the large muscle mass and ST expression characteristic of this model.     

In vitro long-term culture of human bone under physiological load conditions]

There is evidence that mechanical loading is an important, if not the most important factor influencing bone mass and architecture. Investigations under in vivo conditions and cell culture methods, performed during the last years, helped to elucidate these mechanisms. However, the mechanisms by which load bearing acts on bone tissue are until now not completely understood. It is well accepted that weight-bearing exercise increases bone mass and on the other hand lower physical activity engenders bone loss. But neither a physiological threshold for bone loss or bone growth nor the character of the mechanical stimulus concerning amount, frequency and duration of the applied load are known. Even more speculative is the idea how this signal is transformed into the biological response of growing bone. Three-dimensional bone-culture-systems with simultaneous applied mechanical load enables to improve the knowledge of regulation of bone metabolism. We show the results of a long-term in vitro experiment with human cancellous bone under physiological load conditions.     

New roots for agriculture: exploiting the root phenome

Recent advances in root biology are making it possible to genetically design root systems with enhanced soil exploration and resource capture. These cultivars would have substantial value for improving food security in developing nations, where yields are limited by drought and low soil fertility, and would enhance the sustainability of intensive agriculture. Many of the phenes controlling soil resource capture are related to root architecture. We propose that a better understanding of the root phenome is needed to effectively translate genetic advances into improved crop cultivars. Elementary, unique root phenes need to be identified. We need to understand the 'fitness landscape' for these phenes: how they affect crop performance in an array of environments and phenotypes. Finally, we need to develop methods to measure phene expression rapidly and economically without artefacts. These challenges, especially mapping the fitness landscape, are non-trivial, and may warrant new research and training modalities.     

Point-of-service nerve conduction studies: an example of industry-driven disruptive innovation in health care

Nerve conduction studies (NCS) and needle electromyography are useful and established diagnostic procedures for evaluating patients with signs and symptoms of neuromuscular disease. Although technological advances have occurred since the introduction of commercial electromyography instrumentation in the 1950s, most improvements have been evolutionary and were designed to benefit traditional users--neurologists and physiatrists specializing in electromyography. In the past seven years, instruments have been introduced that automate NCS and thereby enable a broader group of physicians, including internists and orthopedic surgeons, to perform these studies and utilize electromyographic data in the care of their patients. Automated NCS devices are an example of what Clayton Christensen terms a "disruptive innovation." In this article, automated NCS is contrasted with traditional electromyography, and the challenges and opposition to its widespread adoption are explored.     

Bringing next-generation therapeutics to the clinic through synthetic biology

Recent advances in synthetic biology have created genetic tools with the potential to enhance the specificity, dynamic control, efficacy, and safety of medical treatments. Interfacing these genetic devices with human patients may thus bring about more efficient treatments or entirely new solutions to presently intractable maladies. Here we review engineered circuits with clinical potential and discuss their design, implementation, and validation.