Biomedical subjects
Publications and source records attributed to William J Phillips.
This study provides evidence of a new treatment approach for colorectal peritoneal metastases, a condition associated with a worse prognosis than other types of metastases.
Contrast induced nephropathy (CIN) is the third leading cause of hospital acquired renal failure and is associated with significant morbidity and mortality. Chronic kidney disease is the primary predisposing factor for CIN. As estimated glomerular filtration rate<60 ml/1.73 m2 represents significant renal dysfunction and defines patients at high risk. Modifiable risk factors for CIN include hydration status, the type and amount of contrast, use of concomitant nephrotoxic agents and recent contrast administration. The cornerstone of CIN prevention, in both the high and low risk patients, is adequate parenteral volume repletion. In the patient at increased risk for CIN it is often appropriate to withhold potentially nephrotoxic medications, and consider the use of n-acetylcysteine. In patients at increased risk for CIN the use of low or iso-osomolar contrast agents should be utilized and strategies employed to minimize contrast volume. In these patients serum creatinine should be obtained forty-eight hours post procedure and it is often appropriate to continue withholding medications such as metformin or non steroidal anti-inflammatories until renal function returns to normal.
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OBJECTIVE: To report a case in which complete relief of pain associated with gastroparesis, with promotion of gastric emptying, was achieved with administration of phentolamine. CASE SUMMARY: A 37-year-old opiate-tolerant female with a history of recurrent abdominal pain, gastroparesis, cyclic vomiting syndrome, and migraine headaches was admitted to the emergency department (ED) with severe acute abdominal pain, nausea, and vomiting. The patient had been previously implanted with a permanent gastric electrical stimulator and she was adherent to her prokinetic, antiemetic, analgesic, and migraine prophylactic medications. Pain relief was achieved rapidly and completely in the ED with sympatholysis by administration of intravenous phentolamine 0.5 mg/kg over 60 minutes, with continuous cardiac monitoring. At a 2 month follow-up visit, the patient reported chronic pain relief, and a decrease in opiate doses was maintained by oral administration of clonidine 0.1 mg twice daily. DISCUSSION: Gastroparesis represents a difficult treatment challenge because management of gastric dysmotility and the accompanying severe abdominal pain is often mutually exacerbating and ineffective. Sympatholysis by intravenous phentolamine provided profound and immediate relief of acute gastroparesis-related abdominal pain in our patient. The mechanism of phentolamine is believed to be receptor blockade at alpha-adrenergic receptors and, therefore, inhibition of the peripheral sensitizing effects of circulating norepinephrine. Although action at a peripheral nerve level is presumed, modulation of alpha-adrenoreceptors receptors is also possible at the dorsal root ganglion or at other central nervous system sites. CONCLUSIONS: The dramatic relief of acute pain in gastroparesis by phentolamine observed in this case would warrant investigation of a larger, controlled case series. Patients who respond to intravenous sympatholysis may likewise be candidates for longer term sympathetic modulation with oral sympatholytics.
In the early years of diagnostic cardiac catheterization, strict sterile precautions were required for cutdown procedures. Thirteen years ago, when the original guidelines were written, the brachial arteriotomy was still frequently utilized, femoral closure devices were uncommon, "implantables," such as intracoronary stents and PFO/ASD closure devices, were in their infancy, and percutaneous valve replacement was not a consideration. In 2005, the cardiac catheterization laboratory is a complex interventional suite with percutaneous access routine and device implantation standard. Despite frequent device implantation, strict sterile precautions are often not observed. Reasons for this include a decline in brachial artery cutdown, limited postprocedure follow-up with few reported infections, limited use of hats and masks in televised cases, and lack of current guidelines. Proper sterile technique has the potential to decrease the patient infection rate. Hand washing remains the most important procedure for preventing infections. Caps, masks, gowns, and gloves help to protect the patient by maintaining a sterile field. Protection of personnel may be accomplished by proper gowning, gloving, and eye wear, disposal of contaminated equipment, and prevention and care of puncture wounds and lacerations. With the potential for acquired disease from blood-borne pathogens, the need for protective measures is as essential in the cardiac catheterization laboratory as is the standard Universal Precautions, which are applied throughout the hospital. All personnel should strongly consider vaccination for hepatitis B. Maintenance of the cardiac catheterization laboratory environment includes appropriate cleaning, limitation of traffic, and adequate ventilation. In an SCAI survey, members recommended an update on guidelines for infection control in the cardiac catheterization laboratory. The following revision of the original 1992 guidelines is written specifically to address the increased utilization of the catheterization laboratory as an interventional suite with device implantation. In this update, infection protection is divided into sections on the patient, the laboratory personnel, and the laboratory environment. Additionally, specific CDC recommendation sections highlight recommendations from other published guidelines.
We present 2 cases, one adult and one pediatric, of acute migraine headache promptly relieved by intravenous oxytocin. Both cases were typical flares of a chronic intermittent headache pattern with classic vascular symptoms. Pain relief in both cases was rapid and temporally related to oxytocin administration. Vascular headache pathophysiology and possible oxytocin mechanisms of action are discussed.
Ethylene glycol is an inexpensive, readily available substance that may be associated with accidental or intentional toxicity. Toxicity from this substance may be encountered in the military and civilian populations. Because it is highly toxic and can result in death if not treated appropriately, it is imperative to recognize the signs and symptoms of intoxication. Two cases are presented and the diagnosis and treatment of ethylene glycol toxicity are discussed. Fomepizole, a new medication for ethylene glycol toxicity, has changed the management of this poisoning. It increases the elimination half-life of ethylene glycol, thus delaying the formation of toxic metabolites.
The ultimate goal for autoimmune immunotherapy is to achieve a specific downregulation or modification of autoaggressive immune responses while leaving in place the normal repertoire, capable of mediating antimicrobial responses. A multitude of preclinical studies, particularly during the last 15 years, raised hopes that self-antigens could be used to achieve the goal of specific immune modulation. Difficulties associated with the translation of this concept to the clinic revealed inherent limitations of antigen-based immune modulation. To increase the efficiency of antigen-dependent immune modulation, researchers started to investigate novel vectors for antigen delivery. Plasmid vectors, as opposed to protein antigens or peptides, have the ability to trigger prolonged production of limited amounts of antigen in the periphery. However, one complicating factor may be the inherent "danger" signal stimulated by the nature of the unmethylated CpG motifs on bacterial plasmid. Currently, various approaches are being explored to improve the efficacy of response while ameliorating the safety concerns of plasmids as immunotherapeutic tools. This manuscript offers a perspective on such efforts and outlines how the knowledge accumulated in the process will help scientists advance to the next generation of immunotherapeutics.
Over the past decades, there has been significant progress in understanding the mechanisms of autoimmune diseases at a molecular level. Diseases such as juvenile diabetes, multiple sclerosis, celiac disease, rheumatoid arthritis, and others appear to be mediated by pathogenic T cells that recognize self-epitopes and escape natural tolerance. Seminal observations correlating autoimmunity with HLA and disease-associated epitopes, in conjunction with recent characterization of T regulatory (Treg) cells, promoted a renewed interest in antigen or epitope-based methods of interfering with pathogenic autoimmune reactions. Recombinant immunoglobulin-peptides encompassing disease-associated self-epitopes (IgPP) integrate effective targeting of antigen-presenting cells (APCs) with a potential to generate Treg cells and thus are being developed for treatment of selected autoimmune disorders. In the current review, we outline the main features of this new class of active immunotherapeutics and directions of future development.
The transmission of a pain signal from the periphery to the central nervous system is complex and only partially understood. Tissue damage results in peripheral release of endogenous chemicals that can directly activate nociceptive afferent fibers, sensitize nociceptors, or cause increased local extravasation and vasodilatation. These algesiogenic substances may be found in local tissues, plasma, and nerve terminals. Release of these substances may be caused by mechanical injury, radiation, or heat, or release may be stimulated by the by-products of tissue injury (ie, catecholamines or collagen). Peripheral nociceptors may be further sensitized by repeated noxious stimuli. Nociceptive afferents have their neurons in the dorsal root ganglion and contact second-order neurons in the dorsal horn or, less often, in the medulla. Modulation of the pain signal in the dorsal horn involves local inhibitory and facilitatory interneurons as well as diverse excitatory and inhibitory neurotransmitters. The neuronal circuitry in the dorsal horn can change and modulate with time so that pain signals sometimes long outlast the original peripheral tissue injury. This central sensitization is thought to be mediated largely through the NMDA receptor complex.
Methods of treatment are different for acute and chronic pain. For acute pain, analgesics such as nonsteroidal anti-inflammatory drugs and opiates are commonly used, sometimes combined with regional anesthesia, such as peripheral nerve block or peridural local anesthesia. The mechanism of transition from an acute to a chronic pain state is poorly understood. Only NMDA receptor antagonists and epidural morphine have shown relatively consistent results as preemptive analgesics. Agents more successfully used to manage chronic pain include those that modify the neurochemistry of the spinal cord dorsal horn, such as tricyclic antidepressants, anticonvulsants, gamma-amino butyric acid agonists, local anesthetic analogs, and NMDA antagonists. Opiates may be used chronically, but tolerance and lack of efficacy may then develop. In selected patients with refractory chronic pain, centrally administered analgesics may be considered, including opiates, dilute local anesthetic, NMDA receptor antagonists, clonidine, midazolam, baclofen, or calcium channel blockers. For both acute and chronic pain, a single agent may be less effective than combinations of analgesics with different mechanisms of action.