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Background: Plantar fasciitis is a common foot disorder that may be resistant to nonoperative treatment. This study evaluated the use of electrohydraulic high-energy shock waves in patients who failed to respond to a minimum of six months of antecedent nonoperative treatment.Methods: A randomized, placebo-controlled, multiply blinded, crossover study was conducted. Phase 1 consisted of twenty patients who were nonrandomized to treatment with extracorporeal shock waves to assess the phase-2 study protocol. In phase 2, 293 patients were randomized and an additional seventy-one patients were nonrandomized. Following ankle-block anesthesia, each patient received 100 graded shocks starting at 0.12 to 0.22 mJ/mm(2), followed by 1400 shocks at 0.22 mJ/mm(2) with use of a high-energy electrohydraulic shock-wave device. Patients in the placebo group received minimal subcutaneous anesthetic injections and nontransmitted shock waves by the same protocol. Three months later, patients were given the opportunity to continue without further treatment or have an additional treatment. This allowed a patient in the active treatment arm to receive a second treatment and a patient who received the placebo to cross over to the active treatment arm. Patients were followed at least one year after the final treatment.Results: Treatment was successful in seventeen of the twenty phase-1 patients at three months. This improved to nineteen (95%) of twenty patients at one year and was maintained at five years. In phase 2, three months after treatment, sixty-seven (47%) of the 144 actively treated patients had a completely successful result compared with forty-two (30%) of the 141 placebo-treated patients (p = 0.008). At one year, sixty-five of the sixty-seven actively treated, randomized patients maintained a successful result. Thirty-six (71%) of the remaining fifty-one nonrandomized patients had a successful result at three months. For all 289 patients who had one or more actual treatments, 222 (76.8%) had a good or excellent result. No patient was made worse by the procedure.Conclusions: The application of electrohydraulic high-energy shock waves to the heel is a safe and effective noninvasive method to treat chronic plantar fasciitis, lasting up to and beyond one year. [ABSTRACT FROM AUTHOR]

Abstract Background Bariatric surgery is currently the most effective form of obesity management for those whose BMI is greater than 40 (or 35 with co morbidities). A minority of patients, however, either do not show the desired loss of excess weight or show weight regain by follow up. Research highlights some of the reasons for this variability, most of which centres on the absence of any psychological support with patients describing how although surgery fixes their body, psychological issues relating to dietary control, self esteem, coping and emotional eating remain neglected. The present study aims to evaluate the impact of a health psychology led bariatric rehabilitation service (BRS) on patient health outcomes. The bariatric rehabilitation service will provide information, support and mentoring pre and post surgery and will address psychological issues such as dietary control, self esteem, coping and emotional eating. The package reflects the rehabilitation services now common place for patients post heart attack and stroke which have been shown to improve patient health outcomes. Methods/Design The study is a randomised control trial and patients will be allocated to receive either usual care or the bariatric rehabilitation service pre and post bariatric surgery. Follow up measures of weight loss and psychological issues will be taken at baseline (2 weeks preoperatively), 3, 6 and 12 months postoperatively. The contents of the bariatric service and the follow up measures are based on previous pilot work and have been developed further by the research team working closely with two patient support groups (BOSPA & WLSinfo). This study will take place in St Richard's Hospital in Chichester in the UK. Discussion It is predicted that a bariatric rehabilitation service will improve weight loss following surgery and will also facilitate changes in other psychological variables such as quality of life, dietary control, self esteem, coping and emotional eating. This also has cost implications for the NHS and other healthcare providers as improved effectiveness of bariatric surgery reduces the health costs of obese patients in the longer term. Trial registration ClinicalTrials.gov NCT01264120.

Recognition that social, economic, political, and environmental factors directly affect HIV risk and vulnerability has stimulated interest in structural approaches to HIV prevention. Progress in the use of structural approaches has been limited for several reasons: absence of a clear definition; lack of operational guidance; and limited data on the effectiveness of structural approaches to the reduction of HIV incidence. In this paper we build on evidence and experience to address these gaps. We begin by defining structural factors and approaches. We describe the available evidence on their effectiveness and discuss methodological challenges to the assessment of these often complex efforts to reduce HIV risk and vulnerability. We identify core principles for implementing this kind of work. We also provide recommendations for ensuring the integration of structural approaches as part of combined prevention strategies. [ABSTRACT FROM AUTHOR]

Retained surgical sponges or gauzes (RSS) are an uncommon complication of exploratory laparotomy surgery and pose a clinically significant risk to the patient. The purpose of this two-part, prospective, descriptive study was to describe the previously uncharacterized ultrasonographic appearance of RSS in phantom and cadaveric models of the acute postoperative period (24-48 h). For the first part of the study, a gelatin phantom containing a woven gauze with a radiopaque marker (radiopaque gauze), a woven gauze with no marker (nonradiopaque gauze), and a laparotomy sponge with a radiopaque marker (radiopaque sponge) was evaluated with ultrasonography. For the second part of the study, a total of 23 gauzes and sponges (of the aforementioned three types) were placed within the peritoneal cavity of 20 cadavers in one of three randomized locations during an exploratory laparotomy laboratory. The cadavers were imaged with ultrasonography 17 h later and still images and video clips were reviewed. The retained surgical sponges and gauzes in the gelatin phantom displayed multiple hyperechoic layers and variable degrees of distal acoustic shadowing. In cadavers, 100% (23/23) of the retained surgical sponges and gauzes displayed a single hyperechoic layer of variable thickness and distal acoustic shadowing. In 95.6% (22/23) retained sponges and gauzes, there was a thin hypoechoic layer noted superficially to the hyperechoic layer. An improved understanding of the ultrasonographic appearance of retained sponges or gauzes in the acute postoperative period may assist in the identification of these objects., (© 2023 American College of Veterinary Radiology.)

Objective: To determine the outcome in dogs diagnosed with congenital extrahepatic portosystemic shunts (EHPSS) at ≥ 5 years of age treated with medical management only (M) or with surgical attenuation (S). The hypothesis was that dogs undergoing surgical attenuation would have a longer survival time than dogs undergoing medical management only., Animals: 351 dogs definitively diagnosed with EHPSS at ≥ 5 years of age., Procedures: Medical records from 2009 to 2019 at 16 veterinary teaching hospitals were evaluated. Data collected included signalment, clinical signs at diagnosis, clinicopathologic data, surgical and medical treatments, shunt morphology, clinical signs and medical treatments at 6 to 12 months after diagnosis, and survival time., Results: 351 dogs (M, 119 [33.9%]; S, 232 [66.1%]) were included in the study. Survival time was longer with surgery than medical management (hazard ratio, 4.2; M, 3.4 years; S, 10.9 years). Continued clinical signs at 6 to 12 months after diagnosis were more common with medical management (M, 40% [33/88]; S, 14% [21/155]). Continued medical treatments at 6 to 12 months after diagnosis were more common in the medical management group (M, 78% [69/88]; S, 34% [53/155]). Perioperative mortality rate was 7.3%., Clinical Relevance: Dogs diagnosed at ≥ 5 years of age with EHPSS have significantly better survival times and fewer clinical signs with surgical attenuation, compared with medical management. Older dogs have similar surgical mortality rates to dogs of all ages after surgical EHPSS attenuation.

Objective: To determine the diagnostic accuracy of optical coherence tomography (OCT) to assess surgical margins of canine soft tissue sarcoma (STS) and determine the influence of observer specialty and training., Study Design: Blinded clinical prospective study., Animals: Twenty-five dogs undergoing surgical excision of STS., Methods: In vivo and ex vivo surgical margins were imaged with OCT after tumor resection. Representative images and videos were used to generate a training presentation and data sets. These were completed by 16 observers of four specialties (surgery, radiology, pathology, and OCT researchers). Images and videos from data sets were classified as cancerous or noncancerous., Results: The overall sensitivity and specificity were 88.2% and 92.8%, respectively, for in vivo tissues and 82.5% and 93.3%, respectively, for ex vivo specimens. The overall accurate classification for all specimens was 91.4% in vivo and 89.5% ex vivo. There was no difference in accuracy of interpretation of OCT imaging by observers of different specialties or experience levels., Conclusion: Use of OCT to accurately assess surgical margins after STS excision was associated with a high sensitivity and specificity among various specialties. Personnel of all specialties and experience levels could effectively be trained to interpret OCT imaging., Clinical Significance: Optical coherence tomography can be used by personnel of different specialty experience levels and from various specialties to accurately identify canine STS in vivo and ex vivo after a short training session. These encouraging results provide evidence to justify further research to assess the ability of OCT to provide real-time assessments of surgical margins and its applicability to other neoplasms., (© 2020 American College of Veterinary Surgeons.)

Objective: To report the outcomes of dogs with lesions of the genitourinary tract treated by vaginectomy or vulvovaginectomy., Study Design: Multi-institutional retrospective study., Animals: Female dogs that underwent vulvovaginectomy, complete vaginectomy, or subtotal vaginectomy from 2003 to 2018 with complete medical records and a minimum of 60 days follow-up., Methods: Data collected from medical records included preoperative, intraoperative, and postoperative data, such as the occurrence of urinary incontinence (UIC), disease recurrence, and death/euthanasia., Results: This study included 21 dogs. Four dogs had vulvovaginectomy, six had complete vaginectomy, and 11 had a subtotal vaginectomy performed. The mean age at surgery was 9.2 years (SD, 3.3). Thirteen dogs were intact at presentation. Smooth muscle tumors were diagnosed most commonly (10 leiomyomata, three leiomyosarcomas, two leiomyofibromas). The median duration of follow-up was 520 days (range, 71-1955). Major complications requiring revision surgery were recorded in two dogs. Postoperative UIC occurred in six of 21 dogs, resolving spontaneously within 60 days in three dogs. Dogs with malignant tumors (n = 6) survived at least 71 days (median, 626; 95% CI, 71-1245), and recurrence of disease occurred in two dogs. In dogs with benign tumors (n = 15), the median survival time was not reached. These dogs survived at least 104 days and had no recurrence of the disease., Conclusion: Vaginectomy and vulvovaginectomy resulted in prolonged survival and low rates of major complications and UIC., Clinical Significance: This study provides evidence to recommend that the risks of this procedure and expectations should be discussed with clients., (© 2020 The American College of Veterinary Surgeons.)

Background: The risks and long-term effects of acute hip dislocation combined with proximal femoral physeal fractures and epiphysiolysis have been minimally addressed in the literature. This infrequent combination must be understood to avoid the major complications of complete separation of proximal femoral components during attempted reduction and to predict the probable outcome of surgical treatment., Methods: Medical records and imaging were retrospectively reviewed to identify patients with a diagnosis of severe to complete slipped capital femoral epiphysis (CFE) or proximal femoral epiphysiolysis in association with hip dislocation. The focus included possible anatomic/vascular disruption and their consequences., Results: Twelve patients were identified. Nine dislocations were posterior; 3 were anterior. In 4 patients, the intact proximal femur was dislocated posteriorly. In 3 patients only the femoral neck was reduced, whereas the CFE remained dislocated. In 1 patient percutaneous pinning was done in the dislocated position before closed reduction. The reduction was successful. In 7 patients only the CFE (4 patients) or femoral neck (3 patients) was displaced at the initial presentation in the emergency room. One patient presented with posterior dislocation associated with complete separation of both components. Ten patients underwent open reduction and internal fixation. Two patients had closed reduction. Nine patients developed complete avascular necrosis, progressive collapse of the femoral head, and degenerative arthritis. Three subsequently had a total hip arthroplasty. One patient developed ischemic change limited to the femoral neck and a nonunion through the epiphysis. One patient had incomplete ischemic necrosis. Only 1 patient had no evidence of ischemic necrosis., Conclusions: This combination of injuries has several anatomic variations. Leaving the CFE dislocated while reducing only the femoral neck must be avoided. Reduction should be done in the operating room with muscle relaxation. The emergency room is not the venue for reduction. The risk of avascular necrosis is extremely high, whether the separation occurs during the acute dislocation or attempted reduction., Level of Evidence: Level IV-case series (retrospective review).

Background: After any physeal injury, the primary concern is the possibility of some pattern of growth alteration, particularly transphyseal bridging that may cause lasting deformities and impact subsequent patient care. Small areas of physeal bridging, however, may be associated with continued growth, rather than impairment., Methods: Seven patients with small central physeal bridges of the distal femur were identified. Demographic data and imaging studies were reviewed., Results: Radiography identified small, relatively centrally located transphyseal osseous bridging that was associated with a linear (longitudinal) region of osseous density extending from the physeal bridge proximally into the metaphysis. This linear striation disappeared at the metaphyseal/diaphyseal gradation, an area of progression proximally from metaphysis to diaphysis. Only 1 patient had a significant leg length inequality. Magnetic resonance imaging confirmed the intrametaphyseal linear sclerotic bone and its disappearance with diaphyseal remodeling., Conclusions: Small, central transphyseal osseous bridges may form after radiologically confirmed acute physeal injury. Normal physiological (hydrostatic) growth forces can be sufficient to overcome such limited central bridging and allow continued, essentially normal, longitudinal growth., Level of Evidence: Level IV (retrospective case series); anatomic study.

Three skeletally immature patients with scapulothoracic dissociation were reviewed. A 5-year-old child's arm, caught in a conveyor belt, led to complete upper extremity amputation. Multiple fractures, muscular damage, and cutaneous and subcutaneous tissue disruption (degloving) were present throughout the avulsed extremity. Replantation was considered, but not carried out because of these extensive injuries. He was treated with a myoelectric prosthesis. Two older boys had scapulothoracic dissociation (one open, one closed) associated with clavicular diaphyseal fractures following blunt trauma. In each case, the clavicle was stabilized, muscular disruptions were reattached, and bleeding was controlled locally, although no specific major vascular repair was required. There was no return of neurologic function, leaving each patient with a flail upper extremity. One patient and his family eventually elected to have a shoulder disarticulation followed by fitting with a myoelectric prosthesis. The other patient still had a flail extremity at his last evaluation 17 months postinjury, but did not return for subsequent evaluation.

Hyperthermia, as an independent modality or in combination with standard cancer treatments such as chemotherapy and radiation, has been established in vitro and in vivo as an effective cancer treatment. However, despite efforts over the past 25 years, such therapies have never been optimized or widely-accepted clinically. Although methods continue to improve, conventionally-delivered heat (RF, ultrasound, microwave etc) can not be delivered in a tumor selective manner. The development of antibody-targeted, or even nontargeted, biocompatible iron oxide nanoparticles (IONP) now allows delivery of cytotoxic heat to individual cancer cells. Using a murine mouse mammary adenocarcinoma (MTGB) and human colon carcinoma (HT29) cells, we studied the biology and treatment of IONP hyperthermia tumor treatment., Methods: Cancer cells (1 × 10 6 ) with or without iron oxide nanoparticles (IONP) were studied in culture or in vivo via implanted subcutaneously in female C3H mice, Tumors were grown to a treatment size of 150 mm 3 and tumors volumes were measured using standard 3-D caliper measurement techniques. Mouse tumors were heated via delivery of an alternating magnetic field, which activated the nanoparticles, using a cooled 36 mm diameter square copper tube induction coil which provided optimal heating in 1.5 cm wide region of the coil. The IONPs were dextran coated and had a hydrodynamic radius of approximately 100 nm. For the in vivo studies, intra-tumor, peritumor and rectal (core body) temperatures were continually measured throughout the treatment period., Results: Although some eddy current heating was generated in non-target tissues at the higher field strengths, our preliminary IONP hyperthermia studies show that whole mouse AMF exposure @160 KHz and 400 or 550 Oe, for a 20 minutes (heat-up and protocol heating), provides a safe and efficacious tumor treatment. Initial electron and light microscopic studies ( in vitro and in vivo ) showed the 100 nm used in our studies are rapidly taken up and retained by the tumor cells. Additional in vitro studies suggest antibodies can significantly enhance the cellular uptake of IONPs.

The development of medical grade iron oxide nanoparticles (IONP) has renewed interest in hyperthermia cancer therapy. Because of their modifiable size and heating capabilities under an AC magnetic field (alternating magnetic field, AMF), IONPs have the potential to damage or kill cells in a manner more therapeutically efficient than previous hyperthermia techniques. The use of IONPs in hyperthermia cancer therapy has prompted numerous questions regarding the cytotoxic mechanism associated with IONP heat therapy and if such mechanism is different (more or less effective) with respect to conventional hyperthermia techniques.

The use of nanoparticles in medical treatment has prompted the question of their safety. In this study, the pathophysiology and biodistribution of three different concentrations of intravenously-delivered dextran-coated Fe3O4 iron oxide nanoparticles (IONP) were evaluated in mice. Some groups of mice were exposed to an AC magnetic field (AMF) at levels comparable with those proposed for cancer treatments. Iron biodistribution analysis for both AMF and non-AMF treated mice was performed for all three concentrations used (.6 mg Fe/mouse, 1.8 mg Fe/mouse, and 5.6 mg Fe/mouse). Blood urea nitrogen, alanine transaminase, alkaline phosphatase, total serum protein, and creatinine were also assessed at 4 hours, 7 days, and 14 days post-injection. Histological analysis of lung, spleen, heart, liver, and kidney tissue was conducted at 7 and 14 days post-injection. Prussian blue and H&E stains were used to histomorphometrically assess iron content in the tissues studied. Preliminary results demonstrate small temporary elevation in liver enzymes and hepatocyte vacuolization at all iron concentrations studied. Liver and spleen were the primary sites of IONP deposition. None of the animals demonstrated systemic or local toxicity or illness, with or without AMF activation.

Widespread adaptation of small molecule-regulated expression systems requires the development of selective inducer molecules that do not have any significant side effects on the endogenous receptors from which the regulated expression system is derived. Here we report the identification and in vitro validation of a novel inducer-receptor pair for the single-plasmid regulated expression system termed pBRES, which contains the ligand-binding domain from the human progesterone receptor (hPR). A small molecule inducer, BLX-913, has been identified as having a 30-fold lower IC(50) for the human progesterone receptor than mifepristone (MFP), the previously best characterized inducer for pBRES. Using modeling-guided protein engineering, compensatory mutations were installed at positions W755 and V729 (hPR numbering) in the ligand-binding pocket of the pBRES regulator protein (pBRES RP) to accommodate the new inducer and allow induction of transgene expression to levels previously seen with MFP. The improved inducer-pBRES RP complex was validated in vitro by monitoring the induction of luciferase, murine secreted alkaline phosphatase, and human interferon beta transgenes in mouse skeletal muscle cells. The engineered pBRES demonstrated low levels of transgene expression in the absence, and high expression levels in the presence, of the new BLX-913 inducer. Findings presented here allow induction of the pBRES-regulated gene expression system by a compound with markedly lower anti-hPR activity than MFP, the previously best characterized inducer.

The potential synergism and benefit of combined hyperthermia and radiation for cancer treatment is well established, but has yet to be optimized clinically. Specifically, the delivery of heat via external arrays /applicators or interstitial antennas has not demonstrated the spatial precision or specificity necessary to achieve appropriate a highly positive therapeutic ratio. Recently, antibody directed and possibly even non-antibody directed iron oxide nanoparticle hyperthermia has shown significant promise as a tumor treatment modality. Our studies are designed to determine the effects (safety and efficacy) of iron oxide nanoparticle hyperthermia and external beam radiation in a murine breast cancer model., Methods: MTG-B murine breast cancer cells (1 × 10 6 ) were implanted subcutaneous in 7 week-old female C3H/HeJ mice and grown to a treatment size of 150 mm 3 +/- 50 mm 3 . Tumors were then injected locally with iron oxide nanoparticles and heated via an alternating magnetic field (AMF) generator operated at approximately 160 kHz and 400 - 550 Oe. Tumor growth was monitored daily using standard 3-D caliper measurement technique and formula. specific Mouse tumors were heated using a cooled, 36 mm diameter square copper tube induction coil which provided optimal heating in a 1 cm wide region in the center of the coil. Double dextran coated 80 nm iron oxide nanoparticles (Triton Biosystems) were used in all studies. Intra-tumor, peri-tumor and rectal (core body) temperatures were continually measured throughout the treatment period., Results: Preliminary in vivo nanoparticle-AMF hyperthermia (167 KHz and 400 or 550 Oe) studies demonstrated dose responsive cytotoxicity which enhanced the effects of external beam radiation. AMF associated eddy currents resulted in nonspecific temperature increases in exposed tissues which did not contain nanoparticles, however these effects were minor and not injurious to the mice. These studies also suggest that iron oxide nanoparticle hyperthermia is more effective than nonnanoparticle tumor heating techniques when similar thermal doses are applied. Initial electron and light microscopy studies of iron oxide nanoparticle and AMF exposed tumor cells show a rapid uptake of particles and acute cytotoxicity following AMF exposure.

Objective: The primary purpose of the study was to investigate the psychosocial effects of harboring a known but untreated unruptured intracranial aneurysm (UIA), information considered important to the decision of whether to treat or not treat an unruptured aneurysm., Methods: Over a 24-month period, 70 Auckland Hospital patients with UIAs were identified. Of these, 30 completed treatment, 2 patients died before treatment, and 38 were either not treated or treatment was unable to be completed during the time frame of the study. Of this group of 38 untreated UIA patients, 23 were enrolled in the study and were assessed on a brief cognitive screen and a battery of psychosocial measures. Their performance was compared with a group of 26 treated UIA patients., Results: Poorer functioning was reported by the untreated UIA group on most psychosocial measures when compared with the treated UIA group 6 months posttreatment, and 36% of untreated UIA patients presented with a pattern of significant psychosocial impairment when compared with the treated UIA group. Qualitative data from the current study suggested that a factor contributing to the poorer reported psychosocial functioning in the untreated group was past or current fear about their untreated UIA., Conclusion: A decrease in overall quality of life was found to be associated with harboring an identified but untreated UIA. Findings from the current study suggest that further investigation of psychosocial outcome in other groups of untreated UIA patients is warranted. Results also suggest that some untreated UIA patients might benefit from psychological intervention.

The objective of this study was to carry out a detailed investigation of the neurological, neuropsychological, and return-to-work status of treatment for unruptured intracranial aneurysms (UIAs). A prospective design was used to evaluate the outcome of UIA treatment in a group of 26 UIA patients. Over a 24-month period UIA patients were assessed prior to treatment, during hospitalization, at three months and at six months following treatment. Their performance was compared to a group of 20 matched controls. Neurological morbidity as a result of the UIA treatment was 5%, as assessed by the Glasgow Outcome Scale (GOS) or Rankin at 3 months. The Telephone Interview for Cognitive Status (TICS) proved to be unreliable as a measure of cognitive change. Reliability of change analysis was more sensitive than group analysis, and revealed a pattern of cognitive deficits in 10% of patients as a result of the UIA treatment. In addition, 25% of patients reported a change in work role as a result of the UIA treatment. While 10% of patients sustained mild to moderate neurological and cognitive impairments 3 to 6 months following UIA treatment, their deficits were not as wide-ranging nor as severe as those sustained by patients who survive a subarachnoid hemorrhage (SAH).

Secreted extracellular acid sphingomyelinase (sASM) activity has been suggested to promote atherosclerosis by enhancing subendothelial aggregation and retention of low-density lipoprotein (LDL) with resultant foam cell formation. Compounds that inhibit sASM activity, at neutral pH, may prevent lipid retention and thus would be expected to be anti-atherosclerotic. With the goal of identifying novel compounds that inhibit sASM at pH 7.4, a high-throughput screen was performed. Initial screening was run using a modification of a proven system that measures the hydrolysis of radiolabeled sphingomyelin presented in detergent micelles in a 96-well format. Separation of the radiolabeled aqueous phosphorylcholine reaction product from uncleaved sphingomyelin lipid substrate was achieved by chloroform/methanol extraction. During the screening campaign, a novel extraction procedure was developed to eliminate the use of the hazardous organic reagents. This new procedure exploited the ability of uncleaved, radiolabeled lipid substrate to interact with hydrophobic phenyl-sepharose beads. A comparison of the organic-based and the bead-based extraction sASM screening assays revealed Z' factor values ranging from 0.7 to 0.95 for both formats. In addition, both assay formats led to the identification of sub- to low micromolar inhibitors of sASM at pH 7.4 with similar IC(50) values. Subsequent studies demonstrated that both methods were also adaptable to run in a 384-well format. In contrast to the results observed at neutral pH, however, only the organic extraction assay was capable of accurately measuring sASM activity at its pH optimum of 5.0. The advantages and disadvantages of both sASM assay formats are discussed.

Sequence profile and fold recognition methods identified mammalian purple acid phosphatase (PAP), a member of a dimetal-containing phosphoesterase (DMP) family, as a remote homolog of human acid sphingomyelinase (ASM). A model of the phosphoesterase domain of ASM was built based on its predicted secondary structure and the metal-coordinating residues of PAP. Due to the low sequence identity between ASM and PAP (approximately 15%), the highest degree of confidence in the model resides in the metal-binding motifs. The ASM model predicts residues Asp 206, Asp 278, Asn 318, His 425, and His 457 to be dimetal coordinating. A putative orientation for the phosphorylcholine head group of the ASM substrate, sphingomyelin (SM), was made based on the predicted catalysis of the phosphorus-oxygen bond in the active site of ASM and on a structural comparison of the PAP-phosphate complex to the C-reactive protein-phosphorylcholine complex. These complexes revealed similar spatial interactions between the metal-coordinating residues, the metals, and the phosphate groups, suggesting a putative orientation for the head group in ASM consistent with the mechanism considerations. A conserved sequence motif in ASM, NX3CX3N, was identified (Asn 381 to Asn 389) and is predicted to interact with the choline amine moiety in SM. The resulting ASM model suggests that the enzyme uses an SN2-type catalytic mechanism to hydrolyze SM, similar to other DMPs. His 319 in ASM is predicted to protonate the ceramide-leaving group in the catalysis of SM. The putative functional roles of several ASM Niemann-Pick missense mutations, located in the predicted phosphoesterase domain, are discussed in context to the model.

Magnetic resonance imaging (MRI) in children with a presumptive diagnosis of Sever's apophysitis and with continuing pain after conservative treatment demonstrated bone bruising within the trabecular bone of the metaphyseal region adjacent to the calcaneal apophysis. Limited portions of the apophyseal secondary ossification center showed similar increased signal changes. MRI studies following treatment with immobilization showed subsidence or disappearance of the metaphyseal but not any apophyseal signal changes commensurate with improvement in symptoms. Accordingly, the disorder commonly referred to as Sever's ''apophysitis'' may be a metaphyseal trabecular stress fracture, similar to the toddler's calcaneal stress fracture that has minimal or no involvement of the apophyseal ossification center, and thus should not be referred to as an apophysitis. Rather, it appears to be an overuse injury causing microinjury within the developing metaphyseal "equivalent" trabecular bone that has not completely adapted to the changing biologic (biomechanical) requirements of the growing, athletically active child.

The aim of TB control is to break the cycle of transmission by treating TB cases as early and efficiently as possible. In its efforts to promote a model of worldwide TB control, WHO defined specific targets and launched the 'Directly Observed Therapy, Short-course' (DOTS) strategy as the main tool to reach them. However, the diversity of patients' attitudes towards the disease and the extreme variability of access to care, especially in resource-poor countries, are amongst the many factors of social context that profoundly affect the ability of control programmes to implement this policy effectively. There are multiple reports of TB control programmes using various types of intervention to promote adherence and enhance case-holding, but most of these interventions depend on external funding, which bring into question their long-term sustainability. In this paper, we address the problems related to operational variabilities in the implementation of the DOTS strategy in resource-poor countries and question the appropriateness of a universal paradigm for global TB control. This analysis is of particular importance as programmers consider using this model in the delivery of anti-retroviral therapies for the treatment of HIV in resource-limited settings., (Copyright 2004 Blackwell Publishing Ltd)

Background: Patients presenting for treatment of chronic plantar fasciopathy often have bilateral involvement. When various nonoperative treatments fail, subsequent intervention may be problematic, especially since bilateral surgery (bilateral fascial release) may not be realistic because of variable, frequently restrictive postoperative weightbearing limitations., Methods: Twenty-three patients (46 heels) were treated with electrohydraulic high-energy orthotripsy to the plantar entheses of both feet while under the same anesthesia (conscious sedation). Following orthotripsy, all patients immediately were fully weightbearing and resumed normal activities of daily living and work, usually within 24 hours. Progressive return to athletic activities was allowed. Patients were assessed by three outcome parameters: (1) pain measured objectively by a dolorimeter combined with the patient's subjective evaluation of the level of pain; (2) pain after 5 minutes of walking upon arising; and (3) pain with daily activities. All pain measurements were done by the visual analog scale., Results: Patients initially experienced varied pain relief responses. This included earlier pain relief in one heel compared to the other, as well as better pain relief in one heel than the other at the 6- and 12-week evaluations, but with much less variance at the 1-year evaluation. By 3 months following orthotripsy, 28 heels (61%) had good or excellent results. These results were maintained or improved at 1 year. In 18 heels (39%), the outcome was fair or poor. Nineteen heels received a second orthotripsy application; one patient requested a second orthotripsy treatment of only one heel, while nine patients requested a second treatment of both heels. The outcome showed further improvement following the second application of orthotripsy. At 1 year after one or two orthotripsy applications, 19 patients (38 heels) were satisfied with the results in both heels (83%), while four patients (eight heels) still had an unsatisfactory outcome (17%)., Conclusion: Electrohydraulic high-energy orthotripsy is a reasonable nonincisional method for treating patients with bilateral chronic proximal plantar fasciopathy under a single anesthetic without the prolonged nonweightbearing status often recommended for patients following unilateral open or endoscopic fascial release.

Thirty studies published between 1977 and 2001 that focus on outcome following unruptured intracranial aneurysm (UIA) treatment are reviewed. Although findings from these studies suggest outcome from UIA treatment is reasonably good (between 5% and 25% morbidity and between 0-7% mortality), many of the complex issues associated with the treatment of UIAs remain controversial. Most of the studies reviewed address outcome in terms of mortality and neurological morbidity. Very few studies exist which include measures of outcome such as cognitive status, psychosocial functioning and quality of life. Given that patients facing treatment tend to be healthy middle-aged adults with many years of active working and social life ahead of them, it is important to take into account the long-term consequences of either harboring an UIA, or having it treated. The small number of studies that include cognitive, psychosocial and quality of life outcomes are reviewed in some detail and suggestions made for improving future UIA outcome research.

Background: The use of surgically noninvasive application of Orthotripsy (extracorporeal shock waves) for various musculoskeletal disorders is being increasingly utilized. Because most patients have had prolonged symptoms refractory to nonoperative treatments, this study evaluated the effectiveness of electrohydraulic Orthotripsy for chronic proximal plantarfasciitis compared to the duration of symptoms prior to treatment., Methods: Following evaluation for study inclusion (unresponsive symptoms for more than 6 months), qualified patients received Orthotripsy or placebo. The study patients were randomized per described protocol. Additional groups of nonrandomized patients also were studied., Results: In both the randomized and nonrandomized patient groups, those who received Orthotripsy were slightly more likely to have a positive result (complete symptom relief or satisfactory improvement) if symptoms had been present and unresponsive to other nonoperative therapeutic attempts for less than 2 years. The same trend was evident in patients undergoing a second Orthotripsy application. In the placebo group, there was no correlation between symptom duration and outcome. However, when placebo patients crossed over to the treatment arm of the study, the same response was evident: patients with symptoms for less than 2 years were slighty more likely to have a positive therapeutic response. Interestingly, the two patients with the longest duration of symptoms (15 and 18 years) both had complete symptom relief., Conclusions: The longevity of symptoms of chronic proximal plantar fasciopathy had a minimal impact on the likelihood of a positive response to Orthotripsy.

In a prospective study of 435 patients with chronic proximal plantar fasciitis, 283 (65%) had an inferior calcaneal bone spur of variable size evident prior to treatment with electrohydraulic high-energy extracorporeal shock waves (ESW). This included 308 patients who received extracorporeal shock wave treatments and 127 placebo (sham control) patients. At both initial (3 months) and final (12 months) evaluations after receiving ESW, no patient who received shock wave applications had significant disappearance or change in the radiographic appearance of the heel spur. Clinical outcome after ESW was satisfactory in 168 patients (82%) with a radiographically demonstrable inferior heel spur and in 81 patients (79%) without such a heel spur. The results showed no correlation between the presence or absence of the heel spur and the eventual treatment outcome.

Despite the availability of effective treatment, tuberculosis (TB) remains a major cause of death from an infectious disease in the world, particularly in resource-poor countries. Among the chief reasons for this are deficiencies in case tracing and in adherence to treatment. In order to investigate the contribution of non-biological factors to these deficiencies, we carried out a qualitative study in The Gambia, West Africa, from October 2000 to March 2001. The methods used were focus group discussions, interviews, participant and non-participant observation, and case histories. Four domains were distinctively investigated: the TB patients, the community, the health care providers (including programme staff), and the donors and policy makers. Analysis of the data from all these sources indicated the contribution of a wide range of socio-anthropological factors which influence the success or otherwise of the TB control programme in The Gambia, i.e. gender, urban/rural residence, recourse to traditional healers, adherence to national health policies, knowledge about TB, migration, and socio-economic factors. It is concluded that all these factors must be taken into account in formulating interventions to improve detection of TB cases and patient adherence to treatment within the framework of the national TB control programmes, and proposals have been made for targeted interventions.

The Revised National Tuberculosis Control Programme (RNTCP), which incorporated the WHO DOTS strategy was introduced in India in the mid-1990s. An operational research project was conducted between 1996 and 1998 to assess the needs and perspectives of patients and providers in two chest clinics in Delhi, Moti Nagar and Nehru Nagar, during the introduction of the new strategy. This paper reports on the findings of the project, concentrating on information collected from 40 in-depth interviews with patient defaulters and from non-participant observations in clinics and directly observed treatment centres. In Moti Nagar chest clinic, 117 of 1786 (6.5%) patients and 195 of 1890 (10%) patients in Nehru Nagar left care before their treatment was complete. It was argued that the reasons for default stem from a poor correlation between patient and programme needs and priorities, and from particular characteristics of the disease and its treatment. Patient needs that were not met by the health system included convenient clinic timings, arrangements for the provision for treatment in the event of a family emergency and provision for complicated cases like alcoholics. The problems facing the provider were poor interpersonal communication with the health staff, lack of attention and support at the clinic, difficulty for patients to re-enter the system if they missed treatment and, in certain areas, long distances to the clinic. Problems related to diseases were inability of the staff to deal with drug side-effects, and patients' conception of equating well-being with cure. Simple, practical measures could improve the provision of tuberculosis (TB) treatment: more flexible hours, allowances for poor patients to reach the clinics and training health care staff for respectful communication and monitoring drug side-effects. The findings indicate a need to rethink the label of 'defaulter' often given to the patients. The important areas for future operational research is also highlighted.

The long-term skeletal changes and the lack of significant clinical complaints in a 77-year-old woman with nail patella syndrome are described. Fifty-five years previously she was one of the first reported patients. These early patients came from two families with involvement of multiple individuals with the variable constellation of deformities. We reviewed her skeletal natural history and her family history as it related to nail patella syndrome involvement and treatment, and correlated the original premolecular biology description and subsequent long-term follow-up with the current molecular and genetic concepts of the cause of the variable expression of nail patella syndrome.

The Revised National Tuberculosis Control Programme (RNTCP), based on the World Health Organization's DOTS strategy,* was introduced in India in the mid-1990s. This paper reports the findings from operational research studies in two pilot sites in New Delhi from 1996 to 1998. A variety of operational research methods were used, including semi-structured interviews, focus group discussions, non-participant observations and collection of data from the tuberculosis registers. The cure rates for the clinics were 71 and 75% with a default rate of 6 and 11%, respectively. An important finding was that health workers screened patients to determine their ability to conform to the direct observation of treatment element of the RNTCP. If the health worker was confident that the patient would comply and/or be easy to trace in the community in the event of 'default', they were provided with short-course treatment under the RNTCP. Other patients, largely those who were in absolute poverty, socially marginalized, itinerant labourers, poorly integrated in the city, were put on standard tuberculosis (TB) treatment as for the previous National TB Programme. The programme was evidently excluding the most vulnerable from the best available care. These findings demonstrate the potential dangers of target-driven programmes where there is an absence of support to both frontline health workers and patients. The paper also highlights the importance of operations research in helping to identify problems within TB programmes.

Since the Alma Ata Declaration in 1978, health systems supporting the treatment and control of infectious diseases like leprosy and tuberculosis have been encouraged to 'integrate' into the primary health care structure within countries. Now, more than 20 years later, countries are still grappling with the concept of integration and looking for ways to achieve it. This study reports findings from a leprosy/Tuberculosis/AIDS awareness pilot project conducted by LEPRA India, a leprosy non-governmental organization (NGO), between 1996 and 2000 in Koraput district, Orissa. The project addressed the issue of integration on two levels. On the one hand LEPRA used the context of the project to explore ways in which to integrate TB services into their existing leprosy control structure. On the other hand, lessons from the pilot study were intended to help the organization find ways of linking with the government health care structure. Following a 'qualitative approach', this operations research project assessed the perceptions of communities and providers about leprosy and tuberculosis services. Providers across the spectrum of this plural healthcare system were asked to provide comment on developing stronger networks with each other, with NGOs and with government, while patients and communities were asked to describe the resources available to them and the constraints they face in accessing health care in general, and for leprosy and TB in particular. LEPRA staff from top management to the outreach workers were also approached for their views. Patients and communities noted that physical access to treatment was a major constraint, while the existence of local providers and family support structures facilitated health and health care. Providers expressed a willingness to collaborate (with LEPRA and the government), but lacked training, adequate staff support and the appropriate equipment/technical resources. Also lacking were adequate information campaigns to inform the public about these diseases and their treatment. This information has provided LEPRA with an understanding of how they might best fill gaps in the existing system and therefore assist in the process of integrating services in their own organization and through the primary health care structure. To achieve this aim, LEPRA will increasingly become involved in developing relationships and partnerships with government in the delivery of training and services and in infrastructure development.

Purpose: Utilizing meta-analysis, the authors have reviewed the available literature to assess the biologic and therapeutic effects of shockwaves on patients with chronic plantar fasciitis and the credibility of these published studies., Methods: Meta-analysis is a systematic method for statistical analysis that combines data from various independent studies, allowing the assessment of potential benefits of various treatments when conclusions based on individual studies may be difficult to evaluate. We hypothesized that extracorporeal shockwave therapy provided a reasonable nonoperative therapeutic alternative to surgical intervention in the treatment of chronic proximal plantar fasciitis., Results: Eight of 20 published studies fulfilled our type A to C criteria for acceptable studies of sufficient duration (one year or more after treatment). These eight studies involved 840 patients, with success rates of as much as 88%. The other 12 studies had methodological variables or lack of appropriate follow-up data that would limit their validity, although the success rates were comparable to the A to C studies., Conclusions: This meta-analysis shows that the directed application of shockwaves to the enthesis of the plantar fascia at the inferior calcaneus is a safe and effective nonsurgical method for treating chronic, recalcitrant heel pain syndrome that has been refractory to other commonly used nonoperative therapies. The results suggest that this therapeutic procedure should be considered before any surgical intervention, and may be preferable prior to cortisone injection, which has a recognized risk of rupture of the plantar fascia and a frequent recurrence of symptoms.

Systematic individual neuroanatomical (MRI) and neuropsychological investigations were conducted for nine patients with unilateral neglect persisting at least 3 months after a cerebral vascular accident. The pattern of referrals, together with subsequent investigation, demonstrates that persisting neglect is rare in both right- and left-hemispheric lesioned patients. But while persisting neglect following a left-hemispheric lesion is even rarer than following a right-hemispheric lesion, it does occur. The neuroanatomical results indicate that persisting neglect may be associated with a different pattern of damage from acute neglect. In the nine patients investigated, persisting neglect reflected extensive lesions that involved three or more cortical lobes or subcortical regions. The results support previous findings that parietal lesions are common but not essential for persisting neglect. In the seven of nine neglect patients with parietal lesions, the rostral inferior parietal lobe and the parietal-frontal junction were involved. Of note was the finding that the brain regions most commonly implicated were the basal ganglia and the superior dorsolateral prefrontal cortex (including the frontal eye field). All of the patients with persisting neglect had a range of neuropsychological deficits, including extinction, personal neglect, and anosognosia for one or more aspects of their neglect. Although it was not possible to demonstrate a double dissociation with this pattern of results, the findings indicate that extinction and anosognosia are dissociable into function-specific forms. Most of the neglect patients also had sustained attention deficits, visual memory problems, and visuospatial constructional difficulties.

The DOTS strategy (directly observed therapy, short course) has been the cornerstone of international TB control policy since the early 1990s. This strategy has provided the international community with an advocacy tool to harness funds for TB as well as a method for helping country programs to achieve high cure rates for TB. But as much as the strategy is seen as successful by some, it is perceived as unsuccessful by others. This paper looks at the results of the introduction of DOTS into control programs and discusses research relating to direct observation of treatment. It asks how policies like DOTS are created, and how they are administered and transferred from the international to the national and finally to the local level. The discipline of public health policy is used to interrogate the creation and history of the DOTS strategy in order to find ways of aiding the transfer of the policy to national and local levels. Finally, the paper asks whether the concepts of "control" and "elimination" continue to be useful in the management of infectious diseases. We ask whether it is time to change the perspective to policies that focus more on the context of implementation and the importance of the development of care, integration, and flexibility rather than cure, targets, and short-term solutions.

The objective of the study was to examine the efficacy of limited arthrotomy coupled with open reduction and internal fixation to minimize potential complications of vascular disruption of the capital femoral physis and femoral epiphysis. It was a patient outcome study. Skeletally immature patients with femoral neck fractures were treated according to a protocol in which all patients underwent limited arthrotomy with decompression of the intercapsular hematoma, open reduction and internal fixation. Radiographic and magnetic resonance imaging studies were carried out on patients to assess whether avascular necrosis developed in the postoperative period. Patients were followed for a mean length of 2 years 8 months, with a range of 2 years to 5.5 years. Twelve patients had good results and one had fair results using Ratliff criteria. No patient developed avascular necrosis (ischemic necrosis), coxa vara, nonunion or premature epiphyseal closure. This study supports the hypothesis that limited decompression of the intracapsular hematoma in children with femoral neck fractures may be a factor in obviating the subsequent appearance of ischemic disruption of the epiphysis and physis.

Three hundred two patients with chronic heel pain caused by proximal plantar fasciitis were enrolled in a study to assess the treatment effects consequent to administration of electrohydraulicall-generated extracorporeal shock waves. Symptoms had been present from 6 months to 18 years. Each treated patient satisfied numerous inclusion and exclusion criteria before he or she was accepted into this study, which was approved by the Food and Drug Administration as a randomized, double-blind evaluation of the efficacy of shock wave therapy for this disorder. Overall, at the predetermined evaluation period 3 months after one treatment, 56% more of the treated patients had a successful result by all four of the evaluation criteria when compared with the patients treated with a placebo. This difference was significant and corroborated the fact that this difference in the results was specifically attributable to the shock wave treatment, rather than any natural improvement caused by the natural history of the condition. The current study showed that the directed application of electrohydraulic-generated shock waves to the insertion of the plantar fascia onto the calcaneus is a safe and effective nonsurgical method for treating chronic, recalcitrant heel pain syndrome that has been present for at least 6 months and has been refractory to other commonly used nonoperative therapies. This technology, when delivered using the OssaTron (High Medical Technology, Kreuz-lingen, Switzerland), has been approved by the Food and Drug Administration specifically for the treatment of chronic proximal plantar fasciitis. The results suggest that this therapeutic modality should be considered before any surgical options, and even may be preferable to cortisone injection, which has a recognized risk of rupture of the plantar fascia and recurrence of symptoms.

A shock wave is a transient pressure disturbance that propagates rapidly in three-dimensional space. It is associated with a sudden rise from ambient pressure to its maximum pressure. A significant tissue effect is cavitation consequent to the negative phase of the wave propagation. The current authors summarize the basic physics of shock waves and the physical parameters involved in assessing the amount of energy delivered to the target tissue and in comparing the various high- and low-energy devices being evaluated clinically for musculoskeletal applications.

Extracorporeal shock wave therapy, which now is used routinely for urolithiasis, has gained increasing acceptance in Europe for some musculoskeletal problems and has led to the inception of clinical studies in the United States. The authors have reviewed the available literature to assess the biologic effects of shock waves on human musculoskeletal tissues, the credibility of published studies on therapeutic applications, and the potential for more widespread application of this modality to various skeletal and near-skeletal disorders. The primary advantage of extracorporeal shock wave therapy is its noninvasive nature and seemingly minimal complications when applied to musculoskeletal tissues.

Purpose: The authors performed a cadaveric study on 10 ankles and retrospectively reviewed 29 arthroscopic synovectomies to determine the trajectory, minimal safe distances, and complications using a new approach for posterior ankle arthroscopy., Type of Study: Anatomic study and case series., Materials and Methods: A posterolateral portal was established immediately posterior to the peroneal tendon sheath. While staying within the posterior ankle capsule, an inside-out technique was then used to establish the posteromedial portal directly behind the medial malleolus adjacent to the posterior tibial tendon. The cadaveric ankles were frozen, sectioned, and photographed to measure the proximity of neurovascular structures to these coaxial portals. From 1988 to 1994, arthroscopic synovectomy was performed on 23 patients (29 ankles) with hemophilia using these modified portals., Results: Results of the anatomic study showed that the posterior tibial nerve and posterior tibial artery were located a mean distance of 5.7 mm (SEM, 0.6 mm) and 6.4 mm (SEM, 0.7 mm) from the edge of the cannula, respectively. Neither penetration nor contact of nerve or vessel was observed at either posterior portal. In the 29 clinical cases, posterior capsular synovectomy was achieved arthroscopically with no detectable complications at an average 45-month follow-up., Conclusions: Our anatomic data show that the coaxial portals described here are essentially equidistant to the neurovascular structures compared with conventional portals. Our clinical results suggest that his technique for posteromedial and posterolateral portals is safe, effective, and reproducible.