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The optical atomic clock based on the 5S 1/2  → 5D 5/2 two-photon transition in rubidium is a candidate for a next generation, manufacturable, portable clock that fits in a small size, weight, and power (SWaP) envelope. Here, we report the first two-photon rubidium clock stabilized by detecting 776 nm fluorescence. We also demonstrate the use of a multi-pixel photon counter as a low voltage substitute to a photomultiplier tube in the feedback loop to the clock laser.

Objective:  The aim of this study was to describe an arthroscopic-assisted technique for coxofemoral toggle rod placement, and to report on the feasibility, drill tunnel trajectory and accuracy of tunnel aperture location using this method., Study Design:  Cadaveric pilot study., Sample Population:  Eight coxofemoral joints., Methods:  Craniodorsal coxofemoral joint luxations were artificially created. A simulated open hip reduction and stabilization with a toggle rod were performed through a limited arthrotomy under arthroscopic guidance. Computed tomography scans were performed to evaluate drill hole trajectory across the femoral neck, and joints were disarticulated and photographed. Digital imaging software was used to determine the percent overlap of the drill hole apertures relative to the origin and insertion of the round ligament on the acetabulum and fovea., Results:  The exit point of the tunnel was entirely within the fovea capitis in five of eight femurs, three of eight femoral drill apertures were only partially within the target area. Of the eight acetabular bone tunnels examined, all were centred occupying the acetabular fossa., Conclusions:  Coxofemoral toggle rod placement can be performed under arthroscopic guidance through a limited arthrotomy. Comparable femoral tunnel accuracy with the standard open technique should be achieved with the current method prior to its clinical use., Competing Interests: S.M.M. is a paid consultant for Arthrex. Rest authors declare no conflict of interest., (Thieme. All rights reserved.)

Veterinary resident training in minimally invasive surgery is currently inconsistent and depends on innate psychomotor skills. Simulation training has been shown to effectively increase basic skills, but demonstration of simulation training effects on advanced skills in the operating room is sparse. We aimed to determine if simulation-trained novice surgeons were able to perform laparoscopic suture ligation in live dogs. Three novice laparoscopic surgeons underwent a 12-session simulation training program with subsequent laparoscopic skills testing to demonstrate competency. The median skills scores of trainees and of one experienced surgeon were 417 and 472, respectively. Eighteen healthy client-owned (shelter) dogs were operated on by four surgeons: one experienced American College of Veterinary Surgeons (ACVS) diplomate, two novice ACVS residents, and one novice ACVS diplomate. Laparoscopic ovariectomy was performed with suture ligation of the ovarian pedicles. Successful surgery was defined as no evidence of ovarian vessel bleeding after transection of the pedicles. Simulation-trained novices performed successful suture-ligated ovariectomies in 11/13 dogs (85%), and the experienced surgeon in 5/5 (100%) dogs. Median total ligation time was 30 minutes (range: 17-57), which was not different among surgeons ( p = .118). Median total surgery time was 105 minutes (range: 69-156) for novices and 89 minutes (range: 65-99) for the experienced surgeon ( p = .038). Extensive simulation training including suturing may contribute toward surgery residents being able to perform complex laparoscopic procedures. These results need to be confirmed in larger numbers of trainees.

Optical clocks are emerging as next-generation timekeeping devices with technological and scientific use cases. Simplified atomic sources such as vapor cells may offer a straightforward path to field use, but suffer from long-term frequency drifts and environmental sensitivities. Here, we measure a laboratory optical clock based on warm rubidium atoms and find low levels of drift on the month-long timescale. We observe and quantify helium contamination inside the glass vapor cell by gradually removing the helium via a vacuum apparatus. We quantify a drift rate of 4×10-15/day, a 10 day Allan deviation less than 5×10-15, and an absolute frequency of the Rb-87 two-photon clock transition of 385,284,566,371,190(1970) Hz. These results support the premise that optical vapor cell clocks will be able to meet future technology needs in navigation and communications as sensors of time and frequency.

Objective: To compare the influence of extracorporeal and intracorporeal ligations on the duration of and complications associated with laparoscopic ovariectomy in dogs., Study Design: Prospective randomized experimental study., Animals: Healthy intact female dogs (n = 18)., Methods: The left and right ovarian pedicles of dogs undergoing laparoscopic ovariectomy were randomly assigned to intracorporeal (n = 18) or extracorporeal (n = 18) ligation groups. Surgeries were performed by two American College of Veterinary Surgeons (ACVS) diplomates and two ACVS residents. The time required to place extracorporeal and intracorporeal ligations, duration of surgery, and intraoperative complications were compared between ligation techniques. Postoperative complications were recorded., Results: The time required for intracorporeal ligation (17.3 ± 8.7 minutes) did not differ from that required for extracorporeal ligation (15.1 ± 6.1 minutes; P = .38). The total duration of surgery was 102.7 ± 28.7 minutes including portal placement and veterinary student closure of incisions. Ligation of the ovarian pedicle was successful in 16 of 17 dogs. Intraoperative hemorrhage occurred in three dogs, and postoperative complications were noted in three dogs, without apparent difference between ligation techniques., Conclusion: No difference was identified between extracorporeal and intracorporeal ligations of ovarian pedicles., Clinical Significance: This study does not provide evidence to support one ligation technique rather than the other., (© 2021 The American College of Veterinary Surgeons.)

SGPL1 encodes sphingosine-1-phosphate lyase, the final enzyme of sphingolipid metabolism. In 2017, a condition featuring steroid-resistant nephrotic syndrome and/or adrenal insufficiency associated with pathogenic SGPL1 variants was reported. In addition to the main features of the disease, patients often exhibit a range of neurologic deficits. In a handful of cases, brain imaging results were described. However, high-quality imaging results and a systematic analysis of brain MR imaging findings associated with the condition are lacking. In this study, MR images from 4 new patients and additional published case reports were reviewed by a pediatric neuroradiologist. Analysis reveals recurring patterns of features in affected patients, including isolated callosal dysgenesis and prominent involvement of the globus pallidus, thalamus, and dentate nucleus, with progressive atrophy and worsening of brain lesions. MR imaging findings of abnormal deep gray nuclei, microcephaly, or callosal dysgenesis in an infant or young child exhibiting other typical clinical features of sphingosine-1-phosphate lyase insufficiency syndrome should trigger prompt genetic testing for SGPL1 mutations., (© 2020 by American Journal of Neuroradiology.)

Background and Purpose: Contrast-enhanced MR imaging provides essential information for pediatric imaging applications. We evaluated gadobenate dimeglumine for contrast-enhanced MR imaging of infants younger than 2 years of age., Materials and Methods: Ninety children younger than 2 years of age (including 55 children younger than 1 year) who underwent enhanced MR imaging of the CNS with gadobenate dimeglumine at 0.1 mmol/kg body weight ± 25% by volume were retrospectively enrolled at 2 imaging centers. Safety data were assessed for adverse events and, when available, vital signs and electrocardiogram and clinical laboratory values obtained from 48 hours before until 48 hours after the MR imaging examination. The efficacy of gadobenate dimeglumine-enhanced MR imaging was evaluated prospectively by 3 blinded, unaffiliated readers in terms of the accuracy of combined pre- and postcontrast images relative to precontrast images alone for differentiation of tumor from non-neoplastic disease and the correct diagnosis of specific disease. Differences were tested using the McNemar test. A possible effect of dose on diagnostic accuracy was assessed using the Fisher exact test., Results: Nine nonserious adverse events were reported for 8 (8.8%) patients. Five adverse events occurred in patients 12 months of age or older. All events occurred at least 24 hours after gadobenate dimeglumine administration, and in each case, the investigating radiologist considered that there was no reasonable possibility of a relationship to gadobenate dimeglumine. No clinically meaningful changes in vital signs, electrocardiogram results, or laboratory parameters were reported. Accurate differentiation of tumor from non-neoplastic disease and exact matching of each specific MR imaging-determined diagnosis with the on-site final diagnosis were achieved in significantly more patients by each reader following evaluation of combined pre- and postcontrast images relative to precontrast images alone (91.0%-94.4% versus 75.3%-87.6%, P  < .04, and 66.3%-73.0% versus 52.8%-58.4%, P  < .02, respectively). No significant differences ( P  > .133) in diagnostic accuracy were noted between patients receiving ≤0.08 mmol/kg of gadobenate dimeglumine and patients receiving >0.08 mmol/kg of gadobenate dimeglumine., Conclusions: Gadobenate dimeglumine is safe and effective for pediatric MR imaging., (© 2019 by American Journal of Neuroradiology.)

Pedicle aplasia is an uncommon congenital anomaly most frequently involving the absence of a single pedicle at a single vertebral level. Bilateral pedicle aplasia at multiple levels is exceedingly rare and has only been described once previously in the literature. While single-level pedicle aplasia is often asymptomatic and discovered incidentally, pedicle aplasia of multiple levels may produce severe spinal deformities and neurological deficits. Due to the rarity of this condition, optimal management remains uncertain. In this case report, the authors describe the surgical management of a healthy 9-year-old boy who presented with frequent falls, difficulty running, and severe thoracic kyphotic deformity and was found to have bilateral pedicle aplasia from T3 to T9. A review of the literature regarding pedicle aplasia is also presented.

Dynamic MR imaging was used to evaluate a cervical syrinx in an adolescent boy with an associated hindbrain herniation. Null artifacts were present on one of the sequences that allowed simultaneous high-resolution visualization of syrinx fluid motion and the anatomy of the syrinx walls. A brief review of the theories of syrinx formation and propagation is provided with a comment on why the Williams "slosh" theory of syrinx progression is supported by our unique imaging., (© 2017 by American Journal of Neuroradiology.)

Background: Accelerometer-based activity monitoring is a promising new tool in veterinary medicine used to objectively assess activity levels in dogs. To date, it is unknown how device orientation, attachment method, and attachment of a leash to the collar holding an accelerometer affect canine activity data. It was our goal to evaluate whether attachment methods of accelerometers affect activity counts. Eight healthy, client-owned dogs were fitted with two identical neck collars to which two identical activity monitors were attached using six different methods of attachment. These methods of attachment evaluated the use of a protective case, positioning of the activity monitor and the tightness of attachment of the accelerometer. Lastly, the effect of leash attachment to the collar was evaluated. For trials where the effect of leash attachment to the collar was not being studied, the leash was attached to a harness. Activity data obtained from separate monitors within a given experiment were compared using Pearson correlation coefficients and across all experiments using the Kruskal-Wallis Test., Results: There was excellent correlation and low variability between activity monitors on separate collars when the leash was attached to a harness, regardless of their relative positions. There was good correlation when activity monitors were placed on the same collar regardless of orientation. There were poor correlations between activity monitors in three experiments: when the leash was fastened to the collar that held an activity monitor, when one activity monitor was housed in the protective casing, and when one activity monitor was loosely zip-tied to the collar rather than threaded on using the provided metal loop. Follow-up, pair-wise comparisons identified the correlation associated with these three methods of attachment to be statistically different from the level of correlation when monitors were placed on separate collars., Conclusions: While accelerometer-based activity monitors are useful tools to objectively assess physical activity in dogs, care must be taken when choosing a method to attach the device. The attachment of the activity monitor to the collar should utilize a second, dedicated collar that is not used for leash attachment and the attachment method should remain consistent throughout a study period.

Objectives: To gain insight into the frequency, age of onset, and management of cervical cord compression in mucopolysaccharidosis VI (MPS VI)., Methods: Cervical spine magnetic resonance imaging (MRI) data and/or cervical decompression surgery data collected between 30 June 2005 and 1 September 2015 were analyzed from subjects enrolled in the MPS VI Clinical Surveillance Program (CSP) (ClinicalTrials.gov: NCT00214773), an ongoing multicenter, observational, retrospective and prospective registry., Results: Of 213 subjects enrolled in the CSP, 134 (62.9%) had at least one documented cervical spine MRI assessment. An additional four subjects were identified through surgery records alone to yield a study population comprising 138 subjects (mean age at enrollment =15.1years; age range=0.80-65.0years). Cervical cord compression was documented in 101 (75.4%) of the 134 subjects with ≥1 MRI assessment, the majority (95.0%) by the time of the first recorded MRI. In general, subjects with cervical cord compression had significantly lower height Z-scores compared to those without cervical cord compression (p<0.0001); nevertheless, a few subjects of taller stature had documented cervical cord compression at a young age. Most subjects >20years of age (31/33, 93.9%) presented with cervical cord compression. There was an insufficient number of subjects with both pre- and post-enzyme replacement therapy (ERT) MRI data to determine any association between ERT and cervical cord compression. Surgical decompression was performed on 58 subjects (42.0%), with mean age at first surgery of 13.1years. Decompression plus stabilization procedures accounted for 12.1% of surgeries. Eight subjects (13.8%) underwent reoperation. Complications during or following surgery were reported in 3 subjects, with anesthesia-related complications resulting in two deaths., Conclusions: All individuals with MPS VI are at high risk of developing cervical cord compression at an early age. Routine MRI assessments should be initiated from the time of MPS VI diagnosis. The perioperative management of MPS VI patients can be challenging. This study contributes to the understanding of the natural history of MPS VI., (Copyright © 2016 Shire Human Genetic Therapies. Published by Elsevier Inc. All rights reserved.)

Background: Epilepsy with progressive cortical volume loss is described secondary to energy failure such as mitochondrial disorders, infectious, or inflammatory etiologies and associated with temporal lobe epilepsy. Postmortem studies do not support that spontaneous seizures even if present for prolonged periods universally result in cortical volume loss., Main Findings: We describe two children with extratemporal pharmacoresistent epilepsy, slowly progressive gray matter volume loss over several years, and evidence of central nervous system inflammation. Brain magnetic resonance imaging changes and antibody profiles were not typical of a well-defined, antibody-mediated central nervous system syndrome such as N-methyl-D-aspartate receptor encephalitis., Conclusions: These patients illustrate a novel presentation of a subacute inflammatory central nervous system process with epilepsy and progressive cortical volume loss, supporting the role of sequential brain imaging in children with epilepsy., (Copyright © 2015. Published by Elsevier Inc.)

Disorders of CSF dynamics such as syringomyelia and obstructive hydrocephalus can be caused by thin mobile obstructive lesions not visible on traditional MRI sequences. New imaging techniques with balanced steady-state free precession (bSSFP) and dynamic imaging with bSSFP cine allow visualization of these pulsatile structures within the CSF space. The authors present 2 cases involving pediatric patients-one who developed presumed idiopathic syringomyelia and one with presumed communicating hydrocephalus in association with Pfeiffer syndrome-who harbored thin dynamic obstructive lesions seen on bSSFP cine studies using 1.5-T MRI. In combination with traditional CSF cine studies and bSSFP, bSSFP cine sequence was able to detect dynamic membranous adhesions not seen on traditional MRI sequences. These previously undetectable lesions on traditional MRI sequences were the etiology of CSF obstruction, and tailored surgical approaches were performed to avoid shunting in both patients. These reports demonstrate the clinical utility for using these novel imaging tools for the detection of thin adhesions and dynamic lesions in the central nervous system. Balanced SSFP cine sequences can supplement conventional MR modalities to identify these otherwise poorly visualized lesions responsible for presumed communicating hydrocephalus or idiopathic syringomyelia.

Objective: To describe veterinarians' treatment recommendations and decision-making factors for dogs with cranial cruciate ligament disease (CCLD)., Methods: An online survey of American College of Veterinary Surgeons (ACVS)-Diplomates (surgeon group) and primary care veterinarians (practitioner group) was performed. The survey included questions on treatment recommendations for common case scenarios (small or large breed dog with complete or partial CCLD), treatment decision factors, non-surgical treatment options, and actual treatment, if any, provided for a client-owned dog as well as one owned by their family or close friend., Results: The response rate was 42% for the surgeon group (n = 305/723) and four percent for the practitioner group (n = 1145/ 27,771). Extracapsular stabilization (ES) was the most common treatment recommendation for CCLD in small (9.1 kg) breed dogs amongst surgeons and practitioners. Tibial plateau levelling osteotomy (TPLO) was the most common treatment recommendation for CCLD in large (27.2 kg) breed dogs amongst both groups. The two most important treatment decision factors were dog size (78% of practitioners, 69% of surgeons) and activity level (63% of practitioners, 52% of surgeons). The most common treatment provided for a dog of their own or close relation in the surgeon group was TPLO (64%) followed by ES (15%), whereas in the practitioner group it was ES (38%) followed by TPLO (30%)., Clinical Significance: Extracapsular stabilization and TPLO are the most commonly employed surgical procedures in the surveyed population; dog size and activity level (but not age) are the major factors influencing treatment decisions.

The histone H2A-H2B heterodimer is an integral component of the nucleosome. The cellular localization and deposition of H2A-H2B into chromatin is regulated by numerous factors, including histone chaperones such as nucleosome assembly protein 1 (Nap1). We use hydrogen-deuterium exchange coupled to mass spectrometry to characterize H2A-H2B and Nap1. Unexpectedly, we find that at low ionic strength, the α helices in H2A-H2B are frequently sampling partially disordered conformations and that binding to Nap1 reduces this conformational sampling. We identify the interaction surface between H2A-H2B and Nap1 and confirm its relevance both in vitro and in vivo. We show that two copies of H2A-H2B bound to a Nap1 homodimer form a tetramer with contacts between H2B chains similar to those in the four-helix bundle structural motif. The organization of the complex reveals that Nap1 competes with histone-DNA and interhistone interactions observed in the nucleosome, thereby regulating the availability of histones for chromatin assembly., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Mucopolysaccharidosis IVA (MPS IVA), also known as Morquio-Brailsford or Morquio A syndrome, is a lysosomal storage disorder caused by a deficiency of the enzyme N-acetyl-galactosamine-6-sulphate sulphatase (GALNS). MPS IVA is multisystemic but manifests primarily as a progressive skeletal dysplasia. Spinal involvement is a major cause of morbidity and mortality in MPS IVA. Early diagnosis and timely treatment of problems involving the spine are critical in preventing or arresting neurological deterioration and loss of function. This review details the spinal manifestations of MPS IVA and describes the tools used to diagnose and monitor spinal involvement. The relative utility of radiography, computed tomography (CT) and magnetic resonance imaging (MRI) for the evaluation of cervical spine instability, stenosis, and cord compression is discussed. Surgical interventions, anaesthetic considerations, and the use of neurophysiological monitoring during procedures performed under general anaesthesia are reviewed. Recommendations for regular radiological imaging and neurologic assessments are presented, and the need for a more standardized approach for evaluating and managing spinal involvement in MPS IVA is addressed.

Cervical cord compression is a sequela of mucopolysaccharidosis VI, a rare lysosomal storage disorder, and has devastating consequences. An international panel of orthopedic surgeons, neurosurgeons, anesthesiologists, neuroradiologists, metabolic pediatricians, and geneticists pooled their clinical expertise to codify recommendations for diagnosing, monitoring, and managing cervical cord compression; for surgical intervention criteria; and for best airway management practices during imaging or anesthesia. The recommendations offer ideal best practices but also attempt to recognize the worldwide spectrum of resource availability. Functional assessments and clinical neurological examinations remain the cornerstone for identification of early signs of myelopathy, but magnetic resonance imaging is the gold standard for identification of cervical cord compression. Difficult airways of MPS VI patients complicate the anesthetic and, thus, the surgical management of cervical cord compression. All patients with MPS VI require expert airway management during any surgical procedure. Neurophysiological monitoring of the MPS VI patient during complex spine or head and neck surgery is considered standard practice but should also be considered for other procedures performed with the patient under general anesthesia, depending on the length and type of the procedure. Surgical interventions may include cervical decompression, stabilization, or both. Specific techniques vary widely among surgeons. The onset, presentation, and rate of progression of cervical cord compression vary among patients with MPS VI. The availability of medical resources, the expertise and experience of members of the treatment team, and the standard treatment practices vary among centers of expertise. Referral to specialized, experienced MPS treatment centers should be considered for high-risk patients and those requiring complex procedures. Therefore, the key to optimal patient care is to implement best practices through meaningful communication among treatment team members at each center and among MPS VI specialists worldwide., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Rabies has the highest case-fatality rate of all infectious diseases, with 50,000 cases occurring annually worldwide. In 2004 an unvaccinated adolescent survived after novel therapy. We report the management of a child with rabies. Although the implementation of this same therapeutic protocol was successful, the child died after 1 month of hospitalization.

The mucopolysaccharidoses (MPS) represent a group of inheritable, clinically heterogeneous lysosomal storage disorders, in which progressive accumulation of glycosaminoglycans (GAGs) can affect organs and tissues all over the body. The current paper discusses the skeletal X-ray and neuroimaging findings in MPS patients, and the imaging techniques that can be used for diagnosing and monitoring abnormalities in the skeleton and central nervous system. Most MPS types show a typical radiologic expression, called dysostosis multiplex, which manifests as malformations of the skeletal system involving bones in the skull, thorax, spine, pelvis, long bones, and hands. Abnormalities of the spine and GAG deposits in the meninges surrounding the spinal cord can result in spinal cord compression, which, if untreated, can lead to compressive myelopathy. Magnetic resonance imaging (MRI) is the most powerful imaging technique for detecting spinal cord compression, but also radiography and computed tomography are useful. GAG deposits in the brain and surrounding tissues can result in brain anomalies, i.e. white matter lesions, brain atrophy, and hydrocephalus, which can be detected using MRI. Skeletal X-ray and neuroimaging findings can play an important role in diagnosis, follow-up, surgical or medical planning, and assessment of treatment response in MPS patients. There is a need for standardized procedures in evaluating and monitoring neurologic complications in these patients.

In 2004, a teenager survived bat-associated rabies through the Milwaukee protocol (MP). This survivor and another patient with dog-associated rabies were found to have developed deficiencies of tetrahydrobiopterin (BH4) and associated neurotransmitters. BH4 is also essential for neuronal nitric oxide synthase (nNOS), so rabies is predicted to cause constriction of cerebral arteries. We assume that rabies virus, which almost exclusively targets neurons, would disproportionately affect cerebral over systemic perfusion by disrupting nNOS and lead to generalised cerebral artery spasm. Cranial artery vasospasm, therefore, was actively sought in two rabies patients, with the intention to specifically treat with BH4 and L-arginine when necessary. Flow velocities and resistive (RI) or pulsatility indices (PI) of middle cerebral arteries (MCA) were obtained by transcranial doppler ultrasound (TCD). A survival analysis of 8 attempts at the MP is presented. Of these, two cases are reported here. The first case is one child with bat-associated rabies who developed severe bilateral MCAspasm on hospital day (HD)-10 that responded to very low dose (0.2 mcg/kg/min) nitroprusside. The second case, a child with dog-associated rabies, developed spasm of MCA on HD-6 that responded to 6 mg/kg/day BH4. A second spasm with high RI (without cerebral oedema or increased intracranial pressure) responded to 20 mg/kg/day BH4 and 0.5 g/kg/dose L-arginine. Review of the TCD of the first child showed a similar second spasm seven days after first episode. Cerebral artery vasospasm occurred in the two children with rabies, but was clinically silent by standard monitoring. Spasm responded to drugs directed at the NOS pathway. Animal models for treatment of rabies are sorely needed to evaluate therapy.

Traditional medicine has made use of many different plant extracts for treatment of fungal infections and some of these have been tested for in vitro antifungal activity. This systematic review evaluates antifungal herbal preparations that have been tested in controlled clinical trials. Four electronic databases were searched for controlled clinical trials of antifungal herbal medicines. Data were extracted in a standardized manner by two independent reviewers and are reviewed narratively. Seven clinical trials met our inclusion criteria. Tea tree oil preparations were tested in four randomized clinical trials and some positive outcomes were attributed to the intervention in all trials. Solanum species (two trials) and oil of bitter orange preparations (one trial) were compared with conventional treatments. In all cases encouraging results were reported. There are few controlled clinical trials of herbal antifungal medicines. The most thoroughly clinically tested is tea tree oil, which holds some promise. All herbal remedies require further investigation in rigorous clinical trials.

Background: Renal cell carcinoma (RCC) is rare in children and comprises only 1-3% of all pediatric primary renal tumors. Recently, several case reports have described RCC developing in patients previously treated for advanced stage neuroblastoma (NB)., Methods and Results: Our experience with four patients treated for advanced stage NB during early childhood who developed RCC later in life are added to 14 others in the literature., Conclusion: These patients and our review of the literature suggest an association between RCC and NB that warrants further study.

Background and Aims: Many antiviral compounds presently in clinical use have a narrow spectrum of activity, limited therapeutic usefulness and variable toxicity. There is also an emerging problem of resistant viral strains. This study was undertaken to examine the published literature on herbs and plants with antiviral activity, their laboratory evaluation in vitro and in vivo, and evidence of human clinical efficacy., Methods: Independent literature searches were performed on MEDLINE, EMBASE, CISCOM, AMED and Cochrane Library for information on plants and herbs with antiviral activity. There was no restriction on the language of publication. Data from clinical trials of single herb preparations used to treat uncomplicated viral infections were extracted in a standardized, predefined manner., Results: Many hundreds of herbal preparations with antiviral activity were identified and the results of one search presented as an example. Yet extracts from only 11 species met the inclusion criteria of this review and have been tested in clinical trials. They have been used in a total of 33 randomized, and a further eight nonrandomized, clinical trials. Fourteen of these trials described the use of Phyllanthus spp. for treatment of hepatitis B, seven reporting positive and seven reporting negative results. The other 10 herbal medicines had each been tested in between one and nine clinical trials. Only four of these 26 trials reported no benefit from the herbal product., Conclusions: Though most of the clinical trials located reported some benefits from use of antiviral herbal medicines, negative trials may not be published at all. There remains a need for larger, stringently designed, randomized clinical trials to provide conclusive evidence of their efficacy.

Objectives: Many hundreds of plant extracts have been tested for in vitro antibacterial activity. This review is a critical evaluation of controlled clinical trials of herbal medicines with antibacterial activity., Methods: Four electronic databases were searched for controlled clinical trials of antibacterial herbal medicines. Data were extracted and validated in a standardized fashion, according to predefined criteria, by two independent reviewers., Results: Seven clinical trials met our inclusion criteria. Four of these studies were randomized. Three trials of garlic and cinnamon treatments for Helicobacter pylori infections reported no significant effect. Bacterial infections of skin were treated in four trials. Positive results were reported for an ointment containing tea leaf extract in impetigo contagiosa infections. Two trials of tea tree oil preparations used for acne and methicillin-resistant Staphylococcus aureus, and one trial of Ocimum gratissimum oil for acne, reported results equivalent to conventional treatments., Conclusions: Few controlled clinical trials have been published and most are methodologically weak. The clinical efficacy of none of the herbal medicines has so far been demonstrated beyond doubt. This area seems to merit further study through rigorous clinical trials.

Aims: Laboratory media for the isolation of Campylobacter usually contain various selective agents, designed to allow these bacteria to grow whilst suppressing that of other organisms. For example, cycloheximide has often been incorporated into Campylobacter media to inhibit the growth of fungi. The production and availability of cycloheximide, however, has recently decreased due to concerns relating to its potential toxicity for mammalian cells and the compound has also become more expensive as a result. An alternative antifungal agent is necessary, and to address this, the effect of using amphotericin B in place of cycloheximide in Campylobacter selective broths and agars was examined., Methods and Results: The growth of Campylobacter strains and the suppression of potential competitor organisms in selective broths or on selective agars containing either amphotericin B or cycloheximide was quantified, using pure microbial cultures. The results were then confirmed by testing food and water samples that contained high levels of micro-organisms, including Campylobacter., Conclusions: The results of this study indicate that amphotericin B is a suitable replacement for cycloheximide in Campylobacter selective media.

Aim: This study compared the performance of three Campylobacter enrichment broths: Bolton broth (BB), Campylobacter Enrichment broth (CEB) and Preston broth (PB)., Methods and Results: Pure cultures of target and competitor organisms, and naturally-contaminated food samples, were used to establish the performance of these media. In pure culture the PB supported the growth of the greatest number of strains of Campylobacter spp. but failed to inhibit some competitor organisms. The CEB showed the opposite result, inhibiting all 15 competitor organisms used but failing to support the growth of five Campylobacter strains. By comparison, BB showed the best compromise between inhibition of competitors and growth of Campylobacter., Conclusions: Plates inoculated with BB and CEB food enrichments resulted in more Campylobacter growth than those inoculated with PB, which supported significantly less typical growth (P < or = 0.001). The most common competitor organism isolated from PB was Escherichia coli, and Pseudomonas spp. were frequently isolated from BB and CEB. Both BB and CEB were better than PB for the isolation of Campylobacter from naturally-contaminated foods, although BB yielded more confirmed Campylobacter growth than CEB., Significance and Impact of the Study: This study highlighted differences in performance of media used to isolate Campylobacter spp. from foods.

Campylobacters are the most common cause of bacterial food poisoning in the UK and are prominent in many other countries worldwide. Sources that have acted as vehicles of infection in many outbreaks include milk, water and poultry, and these may contain campylobacter cells that are sublethally injured and not detected by routine laboratory techniques. Current culture media contain antibiotics to suppress competing flora, and injured campylobacter cells are more sensitive to the antibiotics used and may not grow in these selective media. Therefore, the use of selective broth as the primary culture medium may reduce the isolation rate from samples containing injured cells. To examine this, various experiments were carried out using naturally contaminated river water and fresh chicken samples. In these samples, campylobacter cells showed varying degrees of sublethal injury, with the greatest found in water. A delay of four to eight hours before adding antibiotics to broth significantly increased isolation rate, compared with direct culture in selective broth. With chicken, however, significantly better results were obtained with selective broth as the primary medium.

Salmonella enteritidis PT4 was recovered from fingers following the breaking of intact shell eggs artificially contaminated in the contents with the bacterium. Kitchen utensils used to mix egg dishes were salmonella-positive, sometimes after washing. Following the preparation of batter or the mixing of eggs, S. enteritidis was recovered from work surfaces over 40 cm from the mixing bowl. The bacterium survived well in thin, dry films of either batter or egg and, from an initial level of one cell per cm2, could be recovered from formica work surfaces 24 h after contamination.

Polyamines are intracellular cations that are thought to play a role in the regulation of cell growth and differentiation. This study was undertaken to determine if inhibition of ornithine decarboxylase (ODC), the rate-limiting enzyme of polyamine synthesis, suppresses formation of intimal hyperplasia (IH) after arterial injury. Twenty New Zealand white rabbits underwent balloon catheter deendothelialization of a common carotid artery. Treated animals (n = 10) were given alpha-difluoromethylornithine (DFMO), an inhibitor of ODC, ad lib in drinking water as a 2% solution. DFMO was begun 3 days prior to surgery and continued until vessel harvest. Vessels were perfusion-fixed at harvest, 2 (n = 10) and 4 (n = 10) weeks postoperatively. All arteries remained patent. There were no histologic differences in the IH between treated and untreated animals. The intima and media surface areas on serial arterial cross sections were determined using computer-assisted planimetry. There was a significant difference in the IH surface area of injured arteries between untreated and DFMO-treated animals at both 2 (17.6 +/- 2.0 vs 3.0 +/- 1.6 microns 2; P less than or equal to 0.001) and 4 weeks 27.4 +/- 5.6 vs 7.1 +/- 1.8 microns 2; P less than or equal to 0.008). No differences were seen in medial thickness. We conclude that ODC inhibition reduces early development of IH after arterial deendothelialization. These data support the hypothesis that polyamines may be cellular messengers involved in the regulation of IH formation.

The relationship between herpes simplex virus type 1 and mental retardation is explored by studying the antibody levels to this virus in a group of 86 severely and profoundly retarded adults. A tendency towards higher antibody levels is found in patients whose retardation is of unknown aetiology. The relationship of these observations to previous research findings and the possible significance of herpes simplex virus in the aetiology of mental retardation are discussed.

A young infant undergoing balloon angioplasty for pulmonic stenosis developed global right renal infarction as a complication of cardiac catheterization via the femoral vein. A second patient developed segmental infarction of a recently transplanted kidney due to occlusion of a polar artery. Although routine renal sonography of these patients was normal, duplex Doppler sonography documented the absence of renal arterial and venous flow.

The magnetic resonance (MR) features of a splenic artery pseudoaneurysm are described in a patient with recurrent pancreatitis. Correlation of MR, CT, and pathologic findings is made, and the advantage of MR imaging for the diagnosis of vascular abnormalities is outlined.

The real-time ultrasound images of the pancreas in 273 children without pancreatic disease were prospectively analyzed to determine the normal appearance of the pancreas. The dimensions of the head, body, and tail of the pancreas were correlated with patient age, weight, height, and body surface area. Correlation between pancreatic dimensions and patient age was as good as or better than that obtained with the other physical parameters. In general, the normal pancreas had a similar sized head and tail with a thinner body as compared with the abnormal pancreas, and an echogenicity that was equal to or slightly greater than that of the liver. Analysis of the images of 13 patients with pancreatitis showed that the presence of a dilated main pancreatic duct was the most useful feature in suggesting an abnormality. Evaluation of pancreatic size, configuration, and echogenicity was not reliable in the differentiation of the normal from the abnormal pancreas.

Sciatic artery aneurysms (SAAs) develop in a persistent sciatic artery, which is a congenital anomalous continuation of the internal iliac artery and may be the major blood supply to the lower extremity. SAAs may appear clinically with rupture, thrombosis, distal embolization, or compression of the sciatic nerve. We have reviewed our three cases and the literature to delineate those factors that permit correct preoperative diagnosis and appropriate surgical intervention. Our three patients (aged 54 to 82 years) appeared with severe ischemia that resulted in above-knee amputations. The literature reveals 21 patients ranging in age from 35 to 84 years (58% were women). Twenty of those patients had operations, one of which resulted in death, and five in above-knee amputations. Unexplained sciatic or buttock pain, or a palpable "pulsating" buttock mass, suggests an SAA. The diagnosis is confirmed by angiography. The recommended treatment is femoropopliteal bypass grafting followed by ligature or percutaneous endovascular thrombosis of the aneurysm. Early diagnosis and correct surgical therapy are the keys to successful management of SAA.

Carcinoembryonic antigen (CEA) is currently being used as a target antigen in the radioimmunodetection of cancer. Circulating CEA may adversely affect the outcome of such studies by formation of intravascular immune complexes. The following studies were undertaken to expand our knowledge of the production, secretion, and pharmacokinetics of CEA, since these factors should have a direct bearing on the serum levels of CEA encountered in radioimmunodetection. The production of CEA was assessed in nude mice given implants of the T-380 CEA secreting human colon tumor. Serum CEA rose linearly as the tumors enlarged; however, the concentration of CEA per g of extracted tumor remained constant throughout the weight range studied. The secretory rate of the T-380 tumor was determined by surgically removing all blood flow to the liver and gastrointestinal tract of the nude mouse model. This procedure removes the known sites of CEA degradation. Serum CEA levels rose progressively following surgery, the values being directly related to the tumor size. The secretory rate was also proportional to tumor size but was a constant 13.8 +/- 3.6 (S.D.) ng/g tumor/hr when expressed on a per g tumor basis. To determine if the serum levels of CEA observed in patients could be due to unique differences in the clearance rates of each patient's CEA, serum from three patients with CEA levels of 2150, 709, and 58 ng/ml was administered i.v. to groups of mice at the original and diluted concentrations. The kinetics of all samples followed a single exponential clearance pattern with a half-time of about 2.5 hr. This was dramatically different from the kinetics of tumor-extracted CEA which exhibited a multiexponential pattern, the first component having a half-time of 3 min. These data suggest that CEA secreted by a tumor is in some way different from that adhering to the tumor. If the secreted CEA truly has a monoexponential clearance with a fixed rate as the experiments suggest, the absolute values of serum CEA are either entirely a function of the tumor secretory rate, or else the product having the short half-time is not measured in serum samples obtained from patients.