Acute pancreatitis associated with end-stage renal disease

Various reports in the literature have suggested an association between end-stage renal disease (ESRD) and acute pancreatitis. Little information concerning this association has been discussed in the radiological literature. In this report, the authors review their experience with 54 episodes of acute pancreatitis in 34 patients, including 26 treated with maintenance dialysis, six who underwent renal transplantation, and two managed conservatively before definitive therapy. Ten (29%) of these patients died. Thirty-one computed tomographic (CT) and 49 ultrasound (US) studies of 30 patients were reviewed and demonstrated findings ranging from normal anatomy to fulminant necrotizing pancreatitis. Fifteen US examinations were technically inadequate for evaluation of the pancreas. None of the CT scans were technically inadequate. The authors emphasize the need for increased awareness of ESRD as a possible risk factor for the development of acute pancreatitis.     

Two frequent missense mutations in Pendred syndrome

Pendred syndrome is an autosomal recessive disorder characterized by early childhood deafness and goiter. A century after its recognition as a syndrome by Vaughan Pendred, the disease gene ( PDS ) was mapped to chromosome 7q22-q31.1 and, recently, found to encode a putative sulfate transporter. We performed mutation analysis of the PDS gene in patients from 14 Pendred families originating from seven countries and identified all mutations. The mutations include three single base deletions, one splice site mutation and 10 missense mutations. One missense mutation (L236P) was found in a homozygous state in two consanguineous families and in a heterozygous state in five additional non-consanguineous families. Another missense mutation (T416P) was found in a homozygous state in one family and in a heterozygous state in four families. Pendred patients in three non-consanguineous families were shown to be compound heterozygotes for L236P and T416P. In total, one or both of these mutations were found in nine of the 14 families analyzed. The identification of two frequent PDS mutations will facilitate the molecular diagnosis of Pendred syndrome.      

Studies of percutaneous epididymal sperm aspiration (PESA) and intracytoplasmic sperm injection

Four distinct studies were carried out using two data sets ofpercutaneous epididymal sperm aspiration (PESA) and intracytoplasmicsperm injection (ICSI) procedures performed from March 1993to January 1997. In study A, an analysis of 181 ICSI treatmentcycles following PESA revealed a successful epididymal spermretrieval rate of 83%. It confirmed that PESA is an effectivesperm retrieval method and the associated ICSI pregnancy rate(35% per embryo transfer) compared favourably with that of othersperm retrieval methods. In study B, the relevance of a priordiagnostic PESA procedure was ascertained by comparing the spermretrieval rates in two groups of patients having their firstICSI treatment cycle with spermatozoa retrieved through PESA.Group B1 (n=50) had diagnostic PESA prior to the ICSI treatmentcycle PESA procedure, unlike patients in group B2 (n=64) whodid not. The sperm retrieval rate in the treatment cycle procedurewas not different at 90 and 82.8% for groups B1 and B2 respectively.However, the discontinuation of diagnostic PESA is fraught withproblems including liability to medico-legal sanctions. In studyC, analysis of 177 treatment cycles involving PESA and ICSIrevealed a successful sperm retrieval rate by PESA of 82% inthe first cycle, 93% in the second, 96% in the third and 100%in the fourth cycle. The same trend was evident when sperm retrievalwas examined in relation to each of the epididymides. Retrievedspermatozoa were found to be motile in 67-100% of cases andthe frequency of samples containing motile spermatozoa did notdecrease with increase in the number of PESA attempts. Theseresults show that PESA does not jeopardize future epididymalsperm retrieval. In study D, the outcome of treatment with ICSIusing ejaculated spermatozoa (305 cycles) (group D1) was comparedwith that of ICSI using spermatozoa obtained through PESA (54cycles) (group D2). The median age of women in the two groupsof couples was similar (34 years). In group D1, 70% of metaphaseII oocytes were fertilized compared with 61% in group D2 (P<0.01).The cleavage rate and the median numbers of transferred andcryopreserved embryos were similar in both groups. There wasno significant difference between the clinical pregnancy rates(33 and 42% in groups D1 and D2 respectively). Our results showthat the outcome of PESA-ICSI treatment compared favourablywith that of ICSI using ejaculated spermatozoa.     

Efficacy of botulinum toxin in chronic anal fissure

Background Chronic anal fissures (CAF) are caused by anal sphincter hypertonia leading to an ischaemic ulcer. By inducing temporary sphincter relaxation, botulinum toxin (Botox) injection has been shown to heal CAF in approximately 73–96% of cases in clinical trials. Aim This study looks at the efficacy of Botox clinical practice. Methods The medical charts were reviewed of all patients with CAF treated with Botox (30iu injected into the sphincter complex in three 10iu aliquots) in the Ulster Hospital, Dundonald, Northern Ireland between March 1999 and November 2001. Results Fifty-one charts were identified. Four patients failed to attend for review and were excluded from the study. Of the remaining 47 patients, 37 (78.7%) were healed following Botox injection. 10 out of 37 (27.0%) developed a recurrent CAF after a median time of 16.0 months (IQR 3.8–20 months). Eight of these patients opted for repeat Botox injection, which was successful in 7 (87.5%) cases. No adverse effects were reported. Conclusion Botox injection for the treatment of CAF is as effective in clinical practice as reported in clinical trials from specialist centres.     

Onyx embolisation of cavernous sinus dural arteriovenous fistula via direct percutaneous transorbital puncture

The cavernous sinus dural arteriovenous fistulas of three patients were successfully embolised by using Onyx (Onyx Liquid Embolic System, MTI, Irvine, CA, USA) as the sole embolic agent, through direct percutaneous transorbital punctures of the cavernous sinuses. Our early experience suggests that this direct approach, coupled with the unique physical properties of Onyx, is a safe and effective alternative to treat cavernous sinus dural arteriovenous fistulas when the conventional transvenous routes are inaccessible.     

Focused ultrasound excites action potentials in mammalian peripheral neurons in part through the mechanically gated ion channel PIEZO2

Neurons of the peripheral nervous system (PNS) are tasked with diverse roles, from encoding touch, pain, and itch to interoceptive control of inflammation and organ physiology. Thus, technologies that allow precise control of peripheral nerve activity have the potential to regulate a wide range of biological processes. Noninvasive modulation of neuronal activity is an important translational application of focused ultrasound (FUS). Recent studies have identified effective strategies to modulate brain circuits; however, reliable parameters to control the activity of the PNS are lacking. To develop robust noninvasive technologies for peripheral nerve modulation, we employed targeted FUS stimulation and electrophysiology in mouse ex vivo skin-saphenous nerve preparations to record the activity of individual mechanosensory neurons. Parameter space exploration showed that stimulating neuronal receptive fields with high-intensity, millisecond FUS pulses reliably and repeatedly evoked one-to-one action potentials in all peripheral neurons recorded. Interestingly, when neurons were classified based on neurophysiological properties, we identified a discrete range of FUS parameters capable of exciting all neuronal classes, including myelinated A fibers and unmyelinated C fibers. Peripheral neurons were excited by FUS stimulation targeted to either cutaneous receptive fields or peripheral nerves, a key finding that increases the therapeutic range of FUS-based peripheral neuromodulation. FUS elicited action potentials with millisecond latencies compared with electrical stimulation, suggesting ion channel–mediated mechanisms. Indeed, FUS thresholds were elevated in neurons lacking the mechanically gated channel PIEZO2. Together, these results demonstrate that transcutaneous FUS drives peripheral nerve activity by engaging intrinsic mechanotransduction mechanisms in neurons [B. U. Hoffman, PhD thesis, (2019)].

The nervous system is a central command center that governs homeostasis in physiological and pathophysiological states. Virtually all tissues, including the skin, heart, lungs, and gut, and immune organs, such as the bone marrow, spleen, and lymph nodes, are innervated by neurons of the peripheral nervous system (PNS). These specialized neurons serve both afferent functions, sending sensory information to the brain, and efferent roles, delivering neural signals to organs to alter their physiological outputs (1). For example, in the case of injury or infection, PNS neurons represent an essential component of immune responses (2). The intersection between the PNS and effector organs thus represents an ideal target for therapeutic development. Indeed, peripheral neuromodulation devices are approved by the US Food and Drug Administration (FDA) or in clinical trials to treat wide-ranging diseases from depression to rheumatoid arthritis (3). These devices rely on implanted electrodes, which require surgical procedures that inherently carry risk (4, 5). Thus, noninvasive strategies to modulate PNS activity are an appealing alternative to treat chronic diseases.Focused ultrasound (FUS) enables noninvasive neuromodulation of deep brain tissue and has shown promise as a therapeutic tool (6). More than 60 y ago, William Fry and colleagues demonstrated the reversible inhibitory effects of ultrasound on the central nervous system (CNS) of frogs, monkeys, and cats (7–9). Since that pioneering work, stimulation of the CNS with ultrasound has been shown to elicit action potentials in hippocampal slices, noninvasively stimulate intact motor circuits, and display therapeutic potential for seizure disruption in mammals (6, 10–13). Compared to the CNS, the effects of ultrasound stimulation on peripheral nerves are less clear. Ultrasound has been reported to both suppress and augment electrically evoked activity in the mammalian and invertebrate PNS (14–20). Notably, human psychophysical studies revealed that transdermal sonication induced somatic sensations such as touch, thermoreception, and pain, suggesting that ultrasound activates sensory neurons (15, 21–23). In addition, noninvasive sonication of the mouse sciatic nerve elicited muscle activity, indicating that FUS excites motor neurons (24, 25). Moreover, one report showed that sonication of a cat Pacinian corpuscle evoked neural activity consistent with receptor or action potentials (21). Despite these tantalizing studies, a systematic analysis of FUS-activated action potentials in mammalian peripheral neurons is lacking. This gap in knowledge is an impediment to the therapeutic development of PNS ultrasound neuromodulation, as protocols to reliably control neuronal activity have yet to be established despite decades of research efforts.To address this gap, we sought to determine reliable FUS parameters that excite action potentials in mammalian peripheral neurons in intact tissue. We focused on mechanosensory neurons of mouse dorsal root ganglia, whose peripheral axons, or afferents, densely innervate skin and internal organs to convey sensory information to the CNS. Activation of primary sensory neurons gives rise to distinct sensations, including touch, pain, itch, warmth, and cold. These distinct percepts are initiated by an impressive array of somatosensory neuronal subtypes, including multiple classes of mechanoreceptors, thermoreceptors, and nociceptors (or pain-sensing neurons). Peripheral sensory neurons can be further classified based on neurophysiological properties, including conduction velocity (CV), receptive field (RF; the area of skin they innervate), sensory threshold, and firing pattern (26). Thus, these well-studied neurons provide a robust platform for examining the excitatory effects of FUS in intact mammalian tissue.Here, we show that millisecond, high-intensity stimulation of sensory neurons with FUS is sufficient to elicit action potentials in all mechanosensory neurons studied. Moreover, the mechanically gated ion channel PIEZO2 sets the threshold for FUS activation of sensory neurons in peripheral tissues. These results define a parameter space to noninvasively excite sensory neurons in intact tissue and reveal molecular mechanisms that enable the transduction of sonication to neural activation—insights that have the potential to inform the development of neuromodulatory therapeutics.     

ORIGINAL ARTICLE: Pilot comparison of 18F-fluorocholine and 18F-fluorodeoxyglucose PET/CT with conventional imaging in prostate cancer

Introduction: Conventional imaging (CI) is known to have limitations with respect to staging of patients with primary or relapsed prostate cancer. Positron emission tomography/computed tomography (PET/CT) with ¹⁸F-flurodeoxyglucose (FDG) is also often suboptimal because of low tracer avidity, but ¹⁸F-fluorocholine (FCH) appears to be a promising alternative molecular imaging probe. We report a prospective pilot study of PET/CT comparing both tracers for staging and restaging of patients with prostate cancer. Methods: Sixteen prostate cancer patients were evaluated (7 for staging and 9 for restaging). All patients also underwent CI, comprising at least an abdominopelvic CT and a bone scan. All imaging results and other relevant data were extracted from the imaging reports and medical charts. Results: Based on all imaging-detected disease sites, both FCH-PET/CT and FDG-PET/CT (79%) were more sensitive than CI (14%), with the highest number of sites of nodal and distant disease on FCH PET/CT. FCH-PET/CT alone would have provided sufficient clinical information to form an appropriate management plan in 88% of cases, as compared with 56% for CI. Conclusion: FCH-PET/CT has the potential to impact on the management of patients with prostate cancer significantly more often than CI.     

Small bowel trans-vaginal evisceration following vault biopsy: general surgeons beware!

A case-report of vaginal evisceration following vault biopsy is described. This case highlights the importance of good surgical technique when performing a vaginal biopsy in order to avoid this rare, but life-threatening, complication. General surgeons may well be faced with this acute presentation and prompt management is vital in order to preserve the involved small bowel.     

Expression of matrix metalloproteinases 1, 3, and 9 in degenerated long head biceps tendon in the presence of rotator cuff tears: an immunohistological study

Background  

Long head biceps (LHB) degeneration, in combination with rotator cuff tears, can be a source of chronic shoulder pain. LHB tenotomy reduces pain and improves joint function although the pathophysiological context is not well understood. Tendon integrity depends on the extracellular matrix (ECM), which is regulated by matrix metalloproteinases (MMP). It is unclear which of these enzymes contribute to LHB but we chose to study MMP 1, 3, and 9 and hypothesized that one or more of them may be altered in LHB, whether diagnosed preoperatively or intraoperatively. We compared expression of these MMPs in both LHB and healthy tendon samples.