INAUGURAL ARTICLE by a Recently Elected Academy Member:Causes, consequences, and remedies for growth-induced solid stress in murine and human tumors

The presence of growth-induced solid stresses in tumors has been suspected for some time, but these stresses were largely estimated using mathematical models. Solid stresses can deform the surrounding tissues and compress intratumoral lymphatic and blood vessels. Compression of lymphatic vessels elevates interstitial fluid pressure, whereas compression of blood vessels reduces blood flow. Reduced blood flow, in turn, leads to hypoxia, which promotes tumor progression, immunosuppression, inflammation, invasion, and metastasis and lowers the efficacy of chemo-, radio-, and immunotherapies. Thus, strategies designed to alleviate solid stress have the potential to improve cancer treatment. However, a lack of methods for measuring solid stress has hindered the development of solid stress-alleviating drugs. Here, we present a simple technique to estimate the growth-induced solid stress accumulated within animal and human tumors, and we show that this stress can be reduced by depleting cancer cells, fibroblasts, collagen, and/or hyaluronan, resulting in improved tumor perfusion. Furthermore, we show that therapeutic depletion of carcinoma-associated fibroblasts with an inhibitor of the sonic hedgehog pathway reduces solid stress, decompresses blood and lymphatic vessels, and increases perfusion. In addition to providing insights into the mechanopathology of tumors, our approach can serve as a rapid screen for stress-reducing and perfusion-enhancing drugs.     

Reuse of explanted permanent pacemakers donated by funeral homes

Poor patients in developing countries may not receive permanent pacemakers (PPMs) even as lifesaving measures because of their high cost. In this report we examined whether PPMs that were explanted and donated by funeral homes in the United States could be safely and effectively reused in indigent patients in India. With permission from the deceased patients' families, 121 PPMs were explanted and donated by funeral homes for reuse. These PPMs were sterilized and sent for implantation in needy and indigent patients at a charity hospital in Mumbai, India. From the pool of donated 121 PPMs, 53 (88%, 11 single-chamber PPMs, 21%, and 42 dual-chamber PPMs, 79%) were acceptable for reuse and implanted (37 new implants, 70%, and 16 for battery/generator replacement, 30%) in 53 patients (mean ± SD 64 ± 10 years old, 28 women, 53%). Indications for PPM implantation were complete heart block (n = 27, 51%) and sick sinus syndrome (n = 26, 49%). All patients were alive and well postoperatively. No significant complications including infections or device failures occurred over 19 to 1,827 days (mean 661) of follow-up. Of 40 patients (75%) who were followed locally, 4 (10%) died because of nonpacemaker-related causes; time to death was 121 to 750 days (mean 430) after PPM implantation. All except 2 patients (5%) reported marked improvement in their symptoms. There were only 4 patients (8%) who were previously employed, and all were able to resume their manual labor work. Also, of the women, 27 patients (96%) reported improvement in symptoms enabling them to resume regular household chores as housewives after PPM implantation. In conclusion, with proper device sterilization and handling protocols, reuse of explanted PPMs in poor patients in developing countries is safe and effective. Implantation of donated PPMs can not only save lives but also improve quality of life of needy poor patients.     

Cortical Tibial Bone Graft for Nasal Augmentation

Background

This study sought to determine the efficacy of cortical tibial bone graft for nasal augmentation. Nine cases of augmentation rhinoplasty with cortical tibial bone graft are presented.

Methods

This prospective study evaluated the postoperative results of nine patients who underwent augmentation rhinoplasty using cortical tibial bone graft. There were six males and three females aged between 21 and 36 years (mean age 29). All the nine cases were treated through closed rhinoplasty incisions.

Results

Nine patients were operated on and the average follow up was 18 months. The results were favorable. The aesthetic results were gratifying; with good nasal projection in every case without any significant postoperative effects or complications requiring surgery were noted during the follow up.

Conclusion

The findings of this study support the use of cortical tibial bone graft for nasal augmentation although further studies with more sample size are required.     

Rehabilitation after Surgical Treatment for Retinoblastoma: Ocular Prosthesis for a 6‐Month‐Old Child

Maxillofacial prosthetic (MFP) rehabilitation can be especially challenging in a young, precooperative, or behaviorally compromised child presenting with an enucleated eye. Retinoblastoma is the most common intraocular malignancy in childhood and is one of the most common pediatric cancers. Treatment consists of enucleation (or removal of the entire globe) followed by placement of orbital implants. Unrestored anopthalmic sockets exhibit growth retardation and can lead to facial disfigurement. This report describes the challenges faced during rehabilitation of a 6‐month‐old girl with an anophthalmic socket due to enucleation for retinoblastoma. The objective of the MFP team was to provide a custom‐built, acrylic ocular prosthesis in as comfortable and atraumatic manner as possible. The case was a success and underscores the value of a multidisciplinary dental approach for the treatment of children with very special needs.     

Helicobacter pylori in gallbladder mucosa in patients with gallbladder disease

Background

Helicobacter species have been found to be associated with biliary tract diseases. This prospective study was done to determine the prevalence of H. pylori in the biliary tract of patients suffering from gallbladder disease.

Methods

Forty-nine patients undergoing laparoscopic/open cholecystectomy for benign biliary tract diseases were investigated with urea breath test for H. pylori infection of gastric antrum. Bile and gallbladder tissues were studied for presence of H. pylori by rapid urease test, histopathological examination, culture and PCR analysis. Gallbladder specimens from two patients who underwent Whipple??s operation and from 10 cadavers were studied as controls.

Results

The mean (SD) age of patients was 42.4 (11.1) years. Urea breath test was positive in 17 (34.6%) cases. Rapid urease test was negative in all the cases. There was no evidence of H. pylori infection of gallbladder on histopathological examination using H&;E, Giemsa and Warthin Starry stains. H. pylori DNA were detected in 16 patients (32.6%) and none of the 12 controls by PCR analysis (p?=?0.025). The presence of H. pylori DNA in bile and/or gallbladder was associated with positive urea breath test, (p?H. pylori infection of bile and gallbladder.

Conclusions

Nearly three quarters of patients with positive urea breath test have detectable H. pylori DNA in gallbladder tissue. The significance of these findings needs to be further evaluated.     

Alterations in mitochondrial DNA copy number and the activities of electron transport chain complexes and pyruvate dehydrogenase in the frontal cortex from subjects with autism

Autism is a neurodevelopmental disorder associated with social deficits and behavioral abnormalities. Recent evidence suggests that mitochondrial dysfunction and oxidative stress may contribute to the etiology of autism. This is the first study to compare the activities of mitochondrial electron transport chain (ETC) complexes (I–V) and pyruvate dehydrogenase (PDH), as well as mitochondrial DNA (mtDNA) copy number in the frontal cortex tissues from autistic and age-matched control subjects. The activities of complexes I, V and PDH were most affected in autism (n=14) being significantly reduced by 31%, 36% and 35%, respectively. When 99% confidence interval (CI) of control group was taken as a reference range, impaired activities of complexes I, III and V were observed in 43%, 29% and 43% of autistic subjects, respectively. Reduced activities of all five ETC complexes were observed in 14% of autistic cases, and the activities of multiple complexes were decreased in 29% of autistic subjects. These results suggest that defects in complexes I and III (sites of mitochondrial free radical generation) and complex V (adenosine triphosphate synthase) are more prevalent in autism. PDH activity was also reduced in 57% of autistic subjects. The ratios of mtDNA of three mitochondrial genes ND1, ND4 and Cyt B (that encode for subunits of complexes I and III) to nuclear DNA were significantly increased in autism, suggesting a higher mtDNA copy number in autism. Compared with the 95% CI of the control group, 44% of autistic children showed higher copy numbers of all three mitochondrial genes examined. Furthermore, ND4 and Cyt B deletions were observed in 44% and 33% of autistic children, respectively. This study indicates that autism is associated with mitochondrial dysfunction in the brain.     

Low‐level laser therapy for fat layer reduction: A comprehensive review

Background and Objective

Low‐level laser (light) therapy (LLLT) is a noninvasive, nonthermal approach to disorders requiring reduction of pain and inflammation and stimulation of healing and tissue regeneration. Within the last decade, LLLT started being investigated as an adjuvant to liposuction, for noninvasive body contouring, reduction of cellulite, and improvement of blood lipid profile. LLLT may also aid autologous fat transfer procedures by enhancing the viability of adipocytes. However the underlying mechanism of actions for such effects still seems to be unclear. It is important, therefore, to understand the potential efficacy and proposed mechanism of actions of this new procedure for fat reduction.

Materials and Methods

A review of the literature associated with applications of LLLT related to fat layer reduction was performed to evaluate the findings from pre‐clinical and clinical studies with respect to the mechanism of action, efficacy, and safety.

Results

The studies as of today suggest that LLLT has a potential to be used in fat and cellulite reduction as well as in improvement of blood lipid profile without any significant side effects. One of the main proposed mechanism of actions is based upon production of transient pores in adipocytes, allowing lipids to leak out. Another is through activation of the complement cascade which could cause induction of adipocyte apoptosis and subsequent release of lipids.

Conclusion

Although the present studies have demonstrated safety and efficacy of LLLT in fat layer reduction, studies demonstrating the efficacy of LLLT as a stand‐alone procedure are still inadequate. Moreover, further studies are necessary to identify the mechanism of action. Lasers Surg. Med. 45:349–357, 2013. © 2013 Wiley Periodicals, Inc.