Mobile gastrointestinal and endoscopic surgery in rural Ecuador: 20 years' experience of Cinterandes.

INTRODUCTION: Five billion people worldwide do not have timely access to surgical care. Cinterandes is one of the only mobile surgical units in low- and middle-income countries. This paper examines the methodology that Cinterandes uses to deliver mobile surgery. METHODS: Founding and core staff were interviewed, four missions were participated in, and internal documents and records were analysed between 1 May and 1 July 2014. RESULTS: Cinterandes performed 7641 operations over the last 20 years (60% gastrointestinal/laparoscopic), travelling 300,000 km to remote areas of Ecuador. The mobile surgery programme was initiated by a local Ecuadorian surgeon in 1980. Funding was acquired from businesses, private hospitals, and individuals, to fund a low-cost surgical truck, simple equipment, and running costs. The mobile surgical unit is a 24-foot modified Isuzu truck containing a preparation room with general equipment storage and running water, together with an operating room including the operating table, anaesthetic and surgical equipment. Mission structure includes: patient identification by a network of local medical personnel in remote regions; pre-operative assessment at 1 week by core team via teleconsultations; four-day surgical missions; post-operative recovery in tents or a local clinic; post-operative follow-up care by local personnel and remote teleconsultations. The permanent core team includes seven members; lead surgeon, lead anaesthetist, operating-room technician, medical coordinator, driver, general coordinator, and receptionist. Additional support members include seven regular surgeons, residents, medical students, and volunteers. CONCLUSION: Surgery is a very effective way to gain the trust of the community, due to immediate results. Trust opens doors to other programmes (e.g. family medicine). Surgery can be incorporated with all other aspects of health care, which can in turn be incorporated with all other aspects of human development, education, food production and nutrition, housing, work and productivity, communication, and recreation.

Technical Note: A new phantom design for routine testing of Doppler ultrasound.

PURPOSE: The objective of this project is to demonstrate the principle and operation for a simple, inexpensive, and highly portable Doppler ultrasound quality assurance (QA) phantom intended for routine QA testing. A prototype phantom has been designed, fabricated, and evaluated. The phantom described here is powered by gravity alone, requires no external equipment for operation, and produces a stable fluid velocity useful for quality assurance. Many commercially available Doppler ultrasound testing systems can suffer from issues such as a lengthy setup, prohibitive cost, nonportable size, or difficulty in use. This new phantom design aims to address some of these problems and create a phantom appropriate for assessing Doppler ultrasound stability. METHODS: The phantom was fabricated using a 3D printer. The basic design of the phantom is to provide gravity-powered flow of a Doppler fluid between two reservoirs. The printed components were connected with latex tubing and then seated in a tissue mimicking gel. Spectral Doppler waveforms were sampled to evaluate variations in the data, and the phantom was evaluated using high frame rate video to find an alternate measure of mean fluid velocity flowing in the phantom. RESULTS: The current system design maintains stable flow from one reservoir to the other for approximately 7 s. Color Doppler imaging of the phantom was found to be qualitatively consistent with laminar flow. Using pulsed spectral Doppler, the average fluid velocity from a sample volume approximately centered in the synthetic vessel was measured to be 56 cm/s with a standard deviation of 3.2 cm/s across 118 measurements. An independent measure of the average fluid velocity was measured to be 51.9 cm/s with a standard deviation of 0.7 cm/s over 4 measurements. CONCLUSIONS: The developed phantom provides stable fluid flow useful for frequent clinical Doppler ultrasound testing and attempts to address several obstacles facing Doppler phantom testing. Such an ultrasound phantom can make routine testing more approachable for institutions that wish to initiate a Doppler QA program or complement a previously existing QA program.

Development and validation of a GEANT4 radiation transport code for CT dosimetry.

The authors have created a radiation transport code using the GEANT4 Monte Carlo toolkit to simulate pediatric patients undergoing CT examinations. The focus of this paper is to validate their simulation with real-world physical dosimetry measurements using two independent techniques. Exposure measurements were made with a standard 100-mm CT pencil ionization chamber, and absorbed doses were also measured using optically stimulated luminescent (OSL) dosimeters. Measurements were made in air with a standard 16-cm acrylic head phantom and with a standard 32-cm acrylic body phantom. Physical dose measurements determined from the ionization chamber in air for 100 and 120 kVp beam energies were used to derive photon-fluence calibration factors. Both ion chamber and OSL measurement results provide useful comparisons in the validation of the Monte Carlo simulations. It was found that simulated and measured CTDI values were within an overall average of 6% of each other.

Targeted profiling of oral bacteria in human saliva and in vitro biofilms with quantitative real-time PCR.

An in vitro plaque model based on the use of human salivary bacteria and tooth-like surfaces was previously developed for studying the formation of oral biofilm and its use for pre-clinical testing of candidate antimicrobial or antiplaque agents. In this study, a quantitative Taqman PCR assay (QPCR) was developed to compare the bacterial compositions of in vitro biofilms to parent saliva samples, and to determine the relative contributions of different species in the formation of the oral biofilm. In addition, the growth inhibition of saliva-derived plaque was evaluated by chlorhexidine. With this assay, which consisted of primer/probe sets targeting either 16S rDNA sequences present in public databases or cloned ribosomal intergenic spacer region (ISR) sequences, 15 oral bacteria derived from saliva as well as those that were responsible for biofilm formation in an in vitro plaque model were rapidly identified and quantified. Among the target organisms were Actinobacillus actinomycetemcomitans, Eikenella corrodens, Fusobacterium nucleatum, Lactobacillus acidophilus, Micromonas micros, Porphyromonas gingivalis, Prevotella intermedia, Streptococcus mutans, Streptococcus sobrinus, Tannerella forsythensis, and Veillonella parvula. Primer and probe sets developed were both sensitive and specific. The relative profiles of a number of bacteria in 45-h-old biofilms were determined and, when compared to saliva samples, it was found that most of the bacteria identified in saliva also populated the in vitro plaque, including some anaerobes. Brief exposure of biofilms to chlorhexidine resulted in significant losses in viability. This new broad spectrum QPCR assay in combination with the in vitro plaque model will be of significant value in the quantitative study of the microbial composition of human saliva, saliva-derived plaque, and pre-clinical evaluation of potential antimicrobial and antiplaque molecules.

Laparoscopic resection of curable colon and rectal cancer: an evidence-based review.

The initial enthusiastic application of laparoscopic techniques to colorectal surgical procedures was tempered in the early 1990s by reports of tumor implants in the laparoscopic incisions. Substantial evidence has accumulated, including evidence from randomized controlled trials, to support that laparoscopic resection results in oncologic outcomes similar to open resection, when performed by well-trained, experienced surgeons. This review was developed in conjunction with guidelines published by the Society of American Gastrointestinal and Endoscopic Surgeons. Data from the surgical literature concerning laparoscopic resection of curable colorectal cancer was evaluated regarding diagnostic evaluation, preoperative preparation, operative techniques, prevention of tumor implants, and training and experience. Recommendations are accompanied by an assessment of the level of supporting evidence available at the time of the development of the guidelines.

Emulsification preparation of chitosan-urethane microbeads in the presence of a water-soluble blocked diisocyanate, containing furanone homosyrine lactone bacterial inhibitors.

Chitosan is an abundant naturally occurring biopolymer that is biocompatible, of low toxicity and is well suited as a carrier for a range of active agents. Restrictions imposed by this biopolymers unique solubility requirements make if difficult to process. One approach to an internal setting system is to employ the water-soluble blocked isocyanate hexamethylene-1,6-di(aminocarboxysulphonate) (HDACS) in order to cross-link the chitosan and form microspheres in situ utilizing simple emulsion systems. Chitothane microspheres are capable of delivering active agents at controlled release rates and offers a viable alternative to external set methodologies utilizing aldehydes or similar cross-linking agents.

Laparoscopy for appendicitis and cholelithiasis during pregnancy: a new standard of care.

BACKGROUND: Subsequent to a report from the authors' institution, the laparoscopic management of symptomatic cholelithiasis and appendicitis during pregnancy has become the standard of care at LDS Hospital using institutional guidelines. For comparison with previous outcomes described by the authors, 59 additional laparoscopic cases are reported. METHODS: Medical records of all pregnant patients at LDS Hospital who underwent open or laparoscopic cholecystectomy or appendectomy between 1998 and 2002 were reviewed. The outcomes were compared with the authors' previous data. RESULTS: The laparoscopic management of symptomatic cholelithiasis and appendicitis during pregnancy increased from 54% to 97%. No significant differences in preterm delivery rates, birth weights, or 5-min Apgar scores were found between the two periods. No birth defects or uterine injuries occurred. CONCLUSIONS: With the use of the authors' guidelines, laparoscopy has become the standard of care for managing symptomatic cholelithiasis and appendicitis during pregnancy at LDS Hospital without significant increase in morbidity or mortality.

In-vitro release characteristics of tetracycline HCl, khellin and nicotinamide adenine dineculeotide from halloysite; a cylindrical mineral.

The use of halloysite clay as a low cost alternative to more traditional microencapsulation systems is reported. Halloysite is an alumino-silicate clay which demonstrates a predominately cylindrical geometry, uniquely characterized by a hollow core or series of voids with diameters ranging from 16-50 nm. These nanoscale-to-mesoscale microcylinders are capable of entrapping active agents within the core lumen as well as within any void spaces contained in the multilayered walls of the cylinder. Some of the active agents associated with the clay are also bound to the external surfaces of the clay. Delivery of the active agent is first by desorption of the active agent from the exterior surfaces and exposed ends of the microcylinders, and is followed by a second more prolonged phase dominated by pore diffusion from the ends of the cylinders. Halloysite is capable of retaining and releasing a range of active ingredients. Both hydrophilic and hydrophobic agents may be entrapped following appropriate pre-treatment of the clay to render it lipophilic. Here, a unique low cost alternative microcylindrical delivery system: the clay mineral halloysite, is investigated.

Comparison of functional MRI image realignment tools using a computer-generated phantom.

This study discusses the development of a computer-generated phantom to compare the effects of image realignment programs on functional MRI (fMRI) pixel activation. The phantom is a whole-head MRI volume with added random noise, activation, and motion. It allows simulation of realistic head motions with controlled areas of activation. Without motion, the phantom shows the effects of realignment on motion-free data sets. Prior to realignment, the phantom illustrates some activation corruption due to motion. Finally, three widely used realignment packages are examined. The results showed that the most accurate algorithms are able to increase specificity through accurate realignment while maintaining sensitivity through effective resampling techniques. In fact, accurate realignment alone is not a powerful indicator of the most effective algorithm in terms of true activation.

Cortical activation during Braille reading is influenced by early visual experience in subjects with severe visual disability: a correlational fMRI study.

Functional magnetic resonance imaging was performed on blind adults resting and reading Braille. The strongest activation was found in primary somatic sensory/motor cortex on both cortical hemispheres. Additional foci of activation were situated in the parietal, temporal, and occipital lobes where visual information is processed in sighted persons. The regions were differentiated most in the correlation of their time courses of activation with resting and reading. Differences in magnitude and expanse of activation were substantially less significant. Among the traditionally visual areas, the strength of correlation was greatest in posterior parietal cortex and moderate in occipitotemporal, lateral occipital, and primary visual cortex. It was low in secondary visual cortex as well as in dorsal and ventral inferior temporal cortex and posterior middle temporal cortex. Visual experience increased the strength of correlation in all regions except dorsal inferior temporal and posterior parietal cortex. The greatest statistically significant increase, i.e., approximately 30%, was in ventral inferior temporal and posterior middle temporal cortex. In these regions, words are analyzed semantically, which may be facilitated by visual experience. In contrast, visual experience resulted in a slight, insignificant diminution of the strength of correlation in dorsal inferior temporal cortex where language is analyzed phonetically. These findings affirm that posterior temporal regions are engaged in the processing of written language. Moreover, they suggest that this function is modified by early visual experience. Furthermore, visual experience significantly strengthened the correlation of activation and Braille reading in occipital regions traditionally involved in the processing of visual features and object recognition suggesting a role for visual imagery.

In vivo and in vitro proton NMR spectroscopic studies of thiamine-deficient rat brains.

Thiamine deficiency (TD) in rats produces lesions similar to those found in humans with Wernicke's encephalopathy, an organic mental disorder associated with alcoholism. Male Sprague-Dawley rats (n = 24) were deprived of thiamine in a regimen of thiamine-deficient chow and daily intraperitoneal injections of the thiamine antagonist pyrithiamine hydrobromide for 12 days (0.5 mg/kg). In rats with TD, significant changes were observed in the choline peak (reduction and dose-dependent recovery after thiamine replenishment), which was confirmed by the extraction study. Changes were mainly due to the reduction in glycerophosphorylcholine (GPC), suggesting that a reduction in GPC may be relevant to the primary biochemical lesion in TD. These data are compatible with the hypothesis that a decrease in choline compounds is the cause of the biochemical abnormalities that precede neuroanatomic damage characteristic of Wernicke's encephalopathy.

A regulatory cascade of the nuclear receptors FXR, SHP-1, and LRH-1 represses bile acid biosynthesis.

Bile acids repress the transcription of cytochrome P450 7A1 (CYP7A1), which catalyzes the rate-limiting step in bile acid biosynthesis. Although bile acids activate the farnesoid X receptor (FXR), the mechanism underlying bile acid-mediated repression of CYP7A1 remained unclear. We have used a potent, nonsteroidal FXR ligand to show that FXR induces expression of small heterodimer partner 1 (SHP-1), an atypical member of the nuclear receptor family that lacks a DNA-binding domain. SHP-1 represses expression of CYP7A1 by inhibiting the activity of liver receptor homolog 1 (LRH-1), an orphan nuclear receptor that is known to regulate CYP7A1 expression positively. This bile acid-activated regulatory cascade provides a molecular basis for the coordinate suppression of CYP7A1 and other genes involved in bile acid biosynthesis.

The AAPM/RSNA physics tutorial for residents. MR imaging safety considerations. Radiological Society of North America.

Experience and research over the past decade have demonstrated that diagnostic magnetic resonance (MR) imaging is a biologically safe imaging modality. Specifically, there is currently no convincing evidence that there is any long-term or irreversible biologic effects associated with the radiation and magnetic fields used in MR imaging, specifically radio-frequency (RF) radiation, static magnetic fields, and time-varying gradient fields. However, numerous hazards of MR imaging do exist that can cause severe injuries or even death. These hazards are primarily the result of (a) strong magnetic fields and the strong force that they exert on ferromagnetic objects brought into their influence, including interference with electronic devices such as pacemakers and other implanted electronic devices, and (b) RF burns resulting from inadvertently induced currents in conductive loops placed on the patient's skin surface (eg, electrocardiographic leads and other monitoring devices). Other potential concerns are peripheral nerve stimulation resulting from rapidly switched gradients and auditory noise levels. Establishing a complete and coordinated educational program for all MR imaging facility personnel and conducting effective screening and preparation of patients scheduled for MR imaging procedures are essential to avoid accidents and RF burns and to maintain a safe MR imaging facility.

Molecular pharmacology of human alpha1-adrenergic receptors: unique features of the alpha 1a-subtype.

alpha1-Adrenergic receptors (alpha1ARs) are G protein-coupled receptors important in the dynamic component of benign prostatic hyperplasia. alpha1ARs stimulate predominantly phospholipase C-beta, resulting in mobilization of calcium from intracellular stores and, ultimately, smooth muscle contraction. cDNAs encoding three human alpha1ARs (alpha1a, alpha1b, alpha1d) have been cloned, expressed stably in cells, and characterized pharmacologically. Extensive species heterogeneity in tissue distribution emphasizes the importance of studying alpha1ARs in human tissues. Because of the important role of alpha1aARs in mediating prostate smooth muscle contraction, this current review describes alpha1a carboxyl terminal splice variants, examines alpha1AR subtype distribution in various tissues and the role of the putative alpha1LAR in human prostate, provides a brief discussion regarding regulation of this receptor by agonist, and finally discusses implications of distinct alpha1AR subtype distribution in human bladder compared with prostate.

The laparoscopic management of appendicitis and cholelithiasis during pregnancy.

BACKGROUND: Laparoscopic management of appendicitis and symptomatic cholelithiasis during pregnancy remains controversial. We report the single largest series of laparoscopic cholecystectomies and appendectomies during pregnancy. METHODS: Medical records of all pregnant patients who underwent open or laparoscopic management of appendicitis/cholelithiasis at LDS Hospital from 1990 to 1998 were reviewed. RESULTS: Eighteen open appendectomies (OA) and 13 open cholecystectomies (OC) were performed. Forty-five laparoscopic cholecystectomies (LC) and 22 laparoscopic appendectomies (LA) were performed without birth defects, fetal loss or uterine injury. Preterm delivery rates (PTD) in the LA and OA groups were similar (15.8% versus 11.8%, P>0.9). The PTD rate in the LC group was not significantly different than in the OC group (11.9% versus 10.0%, P>0.9). Neither birth weights nor Apgar scores were significantly different across groups. CONCLUSIONS: Laparoscopic management of appendicitis and symptomatic cholelithiasis during pregnancy can be performed with minimal fetal and maternal morbidity when accepted management guidelines are followed.

Alpha1-adrenergic receptor subtypes in human detrusor.

PURPOSE: To identify and quantitate alpha1-adrenergic receptor (alpha1AR) subtype expression in human detrusor. MATERIALS AND METHODS: Initial studies to determine alpha1AR expression in human detrusor were performed using saturation binding with [125I]HEAT. Once the presence of alpha1ARs was documented, subtype (alpha1a, alpha1b, alpha1d) expression at the mRNA level (and comparison with rat) was determined with RNase protection assays (human detrusor) and RT-PCR (human detrusor, rat whole bladder). Competition binding analysis with the alpha1dAR-selective ligand BMY7378 was used to measure alpha1AR subtype expression at a protein level in human detrusor. RESULTS: Alpha1AR expression in human detrusor was low but reproducible (6.3 +/- 1.0 fmol./mg. total protein). RNase protection assays performed on total RNA extracted from human detrusor revealed the following alpha1AR subtype expression: alpha1d (66%) > alpha1a (34%), and no alpha1b. RT-PCR confirmed alpha1AR subtype mRNA distribution in human detrusor with alpha1d (approximately 60-70%) > alpha1a (approximately 30-40%), and a lack of alpha1b mRNA. Rat whole bladder expressed different alpha1AR subtype mRNA than human detrusor, with alpha1a approximately alpha1b approximately alpha1d. The presence of alpha1d > alpha1a expression in human detrusor was confirmed at a protein level by competition analysis utilizing BMY7378 which revealed a two-site fit, with Ki and high affinity binding (66%) consistent with the alpha1dAR subtype. CONCLUSIONS: Human detrusor contained two alpha1AR subtypes (alpha1d > alpha1a), a finding that is different from rat, another commonly used animal model. Since non-subtype selective alpha1AR antagonists ameliorate irritative bladder symptoms (in men and women with/without outlet obstruction), and Rec 15/2739 (alpha1a selective antagonist) does not improve symptom scores in BPH, our findings suggest bladder alpha1dARs may provide a potentially novel mechanism underlying these therapeutic benefits.

Transcriptional regulation of the human alpha1a-adrenergic receptor gene. Characterization Of the 5'-regulatory and promoter region.

We recently cloned cDNAs encoding three subtypes of human alpha1-adrenergic receptors (alpha1ARs), alpha1a, alpha1b, and alpha1d (Schwinn, D. A., Johnston, G. L., Page, S. O., Mosley, M. J., Wilson, K. H., Worman, N. P., Campbell, S., Fidock, M. D., Furness, L. M., Parry-Smith, D. J., Peter, B., and Bailey, D. S. (1995) J. Pharmacol. Exp. Ther. 272, 134-142) and demonstrated predominance of alpha1aARs in many human tissues (Price, D. T., Lefkowitz, R. J., Caron, M. G., Berkowitz, D., and Schwinn, D. A. (1994) Mol. Pharmacol. 45, 171-175). Several lines of evidence indicate that alpha1aARs are important in clinical diseases such as myocardial hypertrophy and benign prostatic hyperplasia. Therefore, we initiated studies to understand mechanisms underlying regulation of alpha1aAR gene transcription. A genomic clone containing 6.2 kb of 5'-untranslated region of the human alpha1aAR gene was recently isolated. Ribonuclease protection and primer extension assays indicate that alpha1aAR gene transcription occurs at multiple initiation sites with the major site located 696 base pairs upstream of the ATG, where a classic initiator sequence is located. Transfection of luciferase reporter constructs containing varying amounts of 5'-untranslated region into human SK-N-MC neuroblastoma cells indicate that a region extending 125 base pairs upstream from the main transcription initiation site contains full alpha1aAR promoter activity. Furthermore, distinct activator and suppressor elements lie 2-3 and 3-5 kilobase pairs upstream, respectively. Although the alpha1aAR promoter contains neither TATA or CAAT elements, gel shift mobility assays targeting three GC boxes immediately upstream of the main transcription initiation site confirm binding of Sp1. Activity of the alpha1aAR promoter is cell-specific, demonstrating highest activity in cells endogenously expressing alpha1aARs. The human alpha1aAR gene also contains several cis regulatory elements, including several insulin and cAMP response elements. Consistent with these observations, we provide the first evidence that treatment of SK-N-MC cells with insulin and cAMP elevating agents leads to an increase in alpha1aAR expression. In conclusion, these data represent the first characterization of the alpha1aAR gene; our findings should facilitate further studies designed to understand mechanisms regulating alpha1AR subtype-specific expression in healthy and diseased human tissue.

Role of noradrenergic hyperactivity in neonatal opiate abstinence.

Despite the existence of a well-defined abstinence syndrome in offspring of opiate-dependent mothers, the mechanisms involved in neonatal abstinence remain unclear. The goal of the present study was to determine the contribution of noradrenergic neurons in the opiate abstinence syndrome in neonatal rats (10 days old). First, the ability of the alpha 2-adrenergic agonist, clonidine to attenuate the symptoms of neonatal opiate abstinence precipitated by naloxone was determined. Secondly, the activity of noradrenergic neurons was determined by measuring postmortem levels of 3-methoxy-4-hydroxyphenylglycol (MHPG) in the hypothalamus, hippocampus and cortex in opiate-abstinent pups. Neonatal opiate abstinence was characterized by an increased incidence of wall climbing, tremors and mouthing. Acute treatment with morphine and naloxone in chronic saline-treated pups also produced the tremor, albeit less severe than in pups treated chronically with morphine. Clonidine (0.2 mg/kg) attenuated the expression of tremor and mouthing in neonates, but increased wall climbing. Clonidine elicited wall climbing in opiate-naive neonates. Treatment with morphine followed by naltrexone increased MHPG levels in all of the brain areas examined, irrespective of the chronic treatment, but naltrexone treatment elicited a larger increase in MHPG levels in pups treated chronically with morphine. Acute morphine treatment increased MHPG levels only in the hypothalamus. The results of the present study provide behavioral and neurochemical data supporting the hypothesis that noradrenergic hyperactivity plays a role in neonatal opiate abstinence.

Application of linear optimization techniques to MRI phase contrast blood flow measurements.

The goal of this study was to use linear optimization techniques as a systematic method of cine phase contrast pulse sequence design and to apply this technique to the measurement of blood flow in vivo. The optimized waveforms were validated in a constant flow phantom with average velocities ranging from 5 to 50 cm/s. The same optimized sequence was also run in a segmented k-space variation with five phase encoding lines per segment. The magnetic resonance (MR) derived velocity measurements were accurate over the entire range of velocities tested (p < .05) in both cases. The same optimized pulse sequence was applied to the measurement of flow in main pulmonary artery of five normal volunteers and compared with stroke volumes and cardiac outputs calculated from right ventricular volume measurements. These measurements showed a mean difference between the MR phase contrast calculated stroke volume and the volumetric stroke volume measurement of 9.8 +/- 11.6%. The mean difference between the calculated phase contrast cardiac output and the volumetric cardiac output was 4.4 +/- 10%. These results imply that optimization techniques are an efficient method for designing cine phase contrast pulse sequences.