Low-dose naltrexone, an opioid-receptor antagonist, is a broad-spectrum analgesic: a retrospective cohort study.

Aim: To evaluate the use of low-dose naltrexone (LDN) as a broad-spectrum analgesic. Methods: Retrospective cohort study from a single pain management practice using data from 2014 to 2020. Thirty-six patients using LDN for ≥2 months were matched to 42 controls. Pain scores were assessed at initial visit and at most recent/final documented visit using a 10-point scale. Results: Cases reported significantly greater pain reduction (-37.8%) than controls (-4.3%; p < 0.001). Whole sample multivariate modeling predicts 33% pain reduction with LDN, with number needed to treat (for 50% pain reduction) of 3.2. Patients with neuropathic pain appeared to benefit even more than those with 'nociceptive'/inflammatory pain. Conclusion: LDN is effective in a variety of chronic pain states, likely mediated by TLR-4 antagonism.

Naltrexone has historically been used to treat various substance use disorders, but recent discoveries have sparked interest in using low-dose naltrexone (LDN) to manage chronic pain. This study compared pain levels reported by patients before and after at least 2 months of LDN treatment to those reported by patients with the same painful diseases, who did not take LDN. Overall, patients who took LDN reported significantly more pain relief than patients who did not take LDN. How LDN alleviates pain seems complex, but apparently involves an anti-inflammatory effect on cells in the brain and spinal cord. LDN is extraordinarily safe, with no known risks (unlike most standard pain medications), and should be studied more in the treatment of chronic pain.

Failure to rescue following proctectomy for rectal cancer: the additional benefit of laparoscopic approach in a nationwide observational study of 44,536 patients.

BACKGROUND: There is growing evidence that failure to rescue (FTR) is an important factor of postoperative mortality (POM) after rectal cancer surgery and surgical approach modified post-operative outcomes. However, the impact of laparoscopy on FTR after proctectomy for rectal cancer remains unknown. The aim of this study was to compare the rates of postoperative complications and FTR after laparoscopy vs open proctectomy for cancer. METHODS: All patients who underwent proctectomy for rectal cancer between 2012 and 2016 were included. FTR was defined as the 90-day POM rate among patients with major complications. Outcomes of patients undergoing open or laparoscopic rectal cancer surgery were compared after 1:1 propensity score matching by year of surgery, hospital volume, sex, age, Charlson score, neoadjuvant chemotherapy, tumor localization and type of anastomosis. RESULTS: Overall, 44,536 patients who underwent proctectomy were included, 7043 of whom (15.8%) developed major complications. The rates of major complications, POM and FTR were significantly higher in open compared to laparoscopic procedure (major complications: 19.2% vs 13.7%, p < 0.001; POM: 5.4% vs 2.3%, p < 0.001; FTR: 13.6% vs 8.3%, p < 0.001; respectively). After matching, open and laparoscopic groups were comparable. Multivariate analysis showed that age, Charlson score, sphincter-preserving procedure and surgical approach were predictive factors for FTR. Open proctectomy was found to be a risk factor for FTR (OR 1.342, IC95% [1.066; 1.689], p = 0.012) compared to laparoscopic procedure. CONCLUSION: When complications occurred, patients operated on by open proctectomy were more likely to die.

Diverting Enterostomy Improves Overall Survival of Patients With Severe Steroid-refractory Gastrointestinal Acute Graft-Versus-Host Disease.

OBJECTIVE: The aim of this study was to evaluate the benefit of diverting enterostomy (DE) in patients with severe steroid-refractory (SR) gastrointestinal acute graft-versus-host-disease (GI-aGVHD) following allogeneic hematopoietic stem-cell transplantation (ASCT). SUMMARY AND BACKGROUND DATA: Severe GI-aGVHD refractory to the first-line steroid therapy is a rare but dramatic life-threatening complication. Second lines of immunosuppressors have limited effects and increase the risk of sepsis. Data suggest that limiting GI bacterial translocation by DE could restrain severe GI-aGVHD. METHODS: From 2004 to 2018, we retrospectively reviewed all consecutive patients undergoing ASCT for hematologic malignancies who developed severe SR GI-aGVHD. We compared patients in whom a proximal DE was performed (Enterostomy group) with those not subjected to DE (Medical group). The primary endpoint was the 1-year overall survival (OS) measured from the onset of GI-aGVHD. Secondary endpoints were the 2-year OS and causes of death. RESULTS: Of the 1295 patients who underwent ASCT, 51 patients with severe SR GI-aGVHD were analyzed (13 in Enterostomy group and 38 in Medical group). Characteristics of patients, transplantation modalities, and aGVHD severity were similar in both groups. The 1-year OS was better after DE (54% vs 5%, P = 0.0004). The 2-year OS was also better in "Enterostomy group" (31% vs 2.5%; P = 0.0015), with a trend to lower death by sepsis (30.8% vs 57.9%; P = 0.091). CONCLUSION: DE should be considered for severe GI-aGVHD as soon as resistance to the corticosteroid is identified.

Cepharanthine: a review of the antiviral potential of a Japanese-approved alopecia drug in COVID-19.

Cepharanthine (CEP) is a naturally occurring alkaloid derived from Stephania cepharantha Hayata and demonstrated to have unique anti-inflammatory, antioxidative, immunomodulating, antiparasitic, and antiviral properties. Its therapeutic potential as an antiviral agent has never been more important than in combating COVID-19 caused by severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) virus. Cepharanthine suppresses nuclear factor-kappa B (NF-κB) activation, lipid peroxidation, nitric oxide (NO) production, cytokine production, and expression of cyclooxygenase; all of which are crucial to viral replication and inflammatory response. Against SARS-CoV-2 and homologous viruses, CEP predominantly inhibits viral entry and replication at low doses; and was recently identified as the most potent coronavirus inhibitor among 2406 clinically approved drug repurposing candidates in a preclinical model. This review critically analyzes and consolidates available evidence establishing CEP's potential therapeutic importance as a drug of choice in managing COVID-19 cases.

Delivering Benefits at Speed Through Real-World Repurposing of Off-Patent Drugs: The COVID-19 Pandemic as a Case in Point.

Real-world drug repurposing-the immediate "off-label" prescribing of drugs to address urgent clinical needs-is a widely overlooked opportunity. Off-label prescribing (ie, for a nonapproved indication) is legal in most countries and tends to shift the burden of liability and cost to physicians and patients, respectively. Nevertheless, health crises may mean that real-world repurposing is the only realistic source for solutions. Optimal real-world repurposing requires a track record of safety, affordability, and access for drug candidates. Although thousands of such drugs are already available, there is no central repository of off-label uses to facilitate immediate identification and selection of potentially useful interventions during public health crises. Using the current coronavirus disease (COVID-19) pandemic as an example, we provide a glimpse of the extensive literature that supports the rationale behind six generic drugs, in four classes, all of which are affordable, supported by decades of safety data, and targeted toward the underlying pathophysiology that makes COVID-19 so deadly. This paper briefly summarizes why cimetidine or famotidine, dipyridamole, fenofibrate or bezafibrate, and sildenafil citrate are worth considering for patients with COVID-19. Clinical trials to assess efficacy are already underway for famotidine, dipyridamole, and sildenafil, and further trials of all these agents will be important in due course. These examples also reveal the unlimited opportunity to future-proof our health care systems by proactively mining, synthesizing, cataloging, and evaluating the off-label treatment opportunities of thousands of safe, well-established, and affordable generic drugs.

No Time to Waste: Real-World Repurposing of Generic Drugs as a Multifaceted Strategy Against COVID-19.

Real-world drug repurposing-the immediate "off-label" prescribing of drugs to address urgent clinical needs-is an indispensable strategy gaining rapid traction in the current COVID-19 crisis. Although off-label prescribing (ie, for a nonapproved indication) is legal in most countries, it tends to shift the burden of liability and cost to physicians and patients, respectively. Nevertheless, in urgent public health crises, it is often the only realistic source of a meaningful potential solution. To be considered for real-world repurposing, drug candidates should ideally have a track record of safety, affordability, and wide accessibility. Although thousands of such drugs are already available, the absence of a central repository of off-label uses presents a barrier to the immediate identification and selection of the safest, potentially useful interventions. Using the current COVID-19 pandemic as an example, we provide a glimpse at the extensive literature that supports the rationale behind six generic drugs, in four classes, all of which are affordable, supported by decades of safety data, and pleiotropically target the underlying pathophysiology that makes COVID-19 so dangerous. Having previously fast-tracked this paper to publication in summary form, we now expand on why cimetidine/famotidine (histamine type-2 receptor antagonists), dipyridamole (antiplatelet agent), fenofibrate/bezafibrate (cholesterol/triglyceride-lowering agents), and sildenafil (phosphodiesterase-5 inhibitor) are worth considering for patients with COVID-19 based on their antiviral, anti-inflammatory, renoprotective, cardioprotective, and anticoagulation properties. These examples also reveal the unlimited opportunity to future-proof public health by proactively mining, synthesizing, and cataloging the off-label treatment opportunities of thousands of safe, well-established, and affordable generic drugs.

Intraplatelet Vascular Endothelial Growth Factor and Platelet-Derived Growth Factor: New Biomarkers in Carcinoembryonic Antigen-Negative Colorectal Cancer?

BACKGROUND/AIM: Colorectal cancer (CRC) is associated with high incidence and mortality rates. Carcinoembryonic antigen (CEA), a prognostic biomarker for recurrent CRC following curative resection, suffers from low sensitivity, especially in early-stage screening. Intraplatelet angiogenesis regulators (IPAR), such as vascular endothelial growth factor (VEGF) and platelet-derived growth factor (PDGF), have been identified as important regulators of tumor growth in CRC. The aim of this study was to confirm the higher preoperative level of IPAR (VEGF and PDGF) in CRC patients compared to controls and to measure IPAR in CEA-negative CRC patients. METHODS: The data and blood of 30 CRC patients and 30 presumably healthy controls were prospectively analyzed and compared. RESULTS: We confirmed elevated preoperative intraplatelet VEGF and PDGF levels in CRC patients compared to controls. Importantly, IPAR were significantly elevated even in CEA-negative CRC patients. CONCLUSION: Elevated preoperative intraplatelet VEGF and PDGF levels in CRC patients suggest new possibilities for postoperative monitoring in CRC patients, especially when CEA is negative.

The Impact of Hospital Volume and Charlson Score on Postoperative Mortality of Proctectomy for Rectal Cancer: A Nationwide Study of 45,569 Patients.

OBJECTIVE: To identify the impact of hospital volume according to Charlson Comorbidity Index (ChCI) on postoperative mortality (POM) after rectal cancer surgery. BACKGROUND: A volume-outcome relationship has been established in complex surgical procedures. However, little is known regarding the impact of hospital volume on POM according to patients' comorbidities after rectal cancer surgery. METHODS: All patients undergoing proctectomy for cancer from 2012 to 2016 were identified in the French nationwide database. Patient condition was assessed on the basis of the validated ChCl and was stratified into 3 groups according to the score (0-2, 3, and ≥4). Chi-square automatic interaction detector (CHAID) was used to identify the cut-off values of the annual proctectomy caseload affecting the 90-day POM. The 90-day POM was analyzed according to hospital volume (low: <10, intermediate: 10-40, and high: ≥41 cases/yr) and ChCI. RESULTS: Among 45,569 rectal cancer resections, the 90-day POM was 3.5% and correlated to ChCI (ChCI 0-2: 1.9%, ChCI 3: 4.9%, ChCI ≥4: 5.8%; P < 0.001). There was a linear decrease in POM with increasing hospital volume (low: 5.6%, intermediate: 3.5%, high: 1.9%; P < 0.001). For low-risk patients (ChCl 0-2), 90-day POM was significantly higher in low and intermediate hospital volume compared with high hospital volume centers (3.2% and 1.8% vs 1.1%; P < 0.001). A significant decrease in postoperative hemorrhage complication rates was observed with increasing center volume (low: 13.3%, intermediate: 11.9%, and high: 9.4%; P < 0.001). After multivariable analysis, proctectomy in low [odds ratio (OR) 2.1, 95% confidence interval (CI) 1.71-2.58, P < 0.001] and intermediate (OR 1.45, 95% CI 1.2-1.75, P < 0.001) hospital volume centers were independently associated with higher risk of mortality. CONCLUSION: The POM after proctectomy for rectal cancer is strongly associated with hospital volume independent of patients' comorbidities. To improve postoperative outcomes, rectal surgery should be centralized.

Persistent perineal sinus after abdominoperineal resection.

BACKGROUND AND AIMS: Persistent perineal sinus (PPS) defined as a perineal wound remaining unhealed more than 6 months after abdominoperineal resection (APR) is a well-known complication. The aim of our study was (1) to evaluate the incidence of PPS after APR for Crohn's disease (CD) in the era of biotherapy, (2) to determine long-term outcome of PPS, (3) to study risk factors associated with delayed perineal healing, and (4) to compare the results in this CD patient group with patients without CD. METHODS: From 1997 to 2013, the records of patients who underwent APR for CD and for non-CD rectal cancer with or without radiochemotherapy at two French university hospitals were studied retrospectively. Perineal healing was evaluated by clinical examination at 1, 6, and 12 months after surgery. RESULTS: The cumulative probability of perineal wound unhealed at 6 and 12 months after surgery was 85 and 48%, respectively, for 81 patients who underwent APR for CD patients in contrast to 21 and 13%, respectively, for 25 non-CD patients with rectal cancer. Eight patients with CD (10%) remained with PPS after a median follow up of 4 years and spontaneous perineal healing occurred with time for all non-CD patients. Factors associated with delayed perineal healing in CD included age at surgery < 49 years (p = 0.001) and colonic-only Crohn's disease location (p = 0.045). Medical treatments had no significant impact on perineal healing. CONCLUSIONS: PPS beyond 6 months post-APR remains a frequent complication but mostly resolves over time. CD is a risk factor for developing PPS and factors associated with higher incidence of PPS were age at surgery < 49 years and colonic-only Crohn's disease location. Prevention of PPS in this population with muscle flap during APR deserves to be evaluated.

Reemergence of Splenectomy for ITP Second-line Treatment?

INTRODUCTION: Corticosteroids are still the standard first-line treatment for immune thrombocytopenic purpura (ITP). As second-line therapy, splenectomy and Rituximab are both recommended. The aim of our study was to compare the efficacy of Rituximab to splenectomy in persistent or chronic ITP patients. METHODS: Between January 1999 and March 2015, we retrospectively selected all consecutive patients who underwent an ITP second-line treatment: Rituximab or splenectomy. The distinction between open (OS) and laparoscopic splenectomy (LS) was analyzed. Primary outcome was composite: hospitalization for bleeding and/or thrombocytopenia and death from hemorrhage or infection. Secondary outcomes were based on response (R) and complete response (CR) rates as defined by the American Society of Hematology. RESULTS: Ninety-six patients were included: 30 patients received Rituximab, 37 underwent OS, and 29 underwent LS. The follow-up was 30, 60, and 120 months in Rituximab, LS, and OS groups, respectively. At 30 month, the primary outcome-free survival rate was higher in splenectomy groups (84% for OS, 86% for LS) than Rituximab group (47%) (P = 0.0002). Similarly, at 30 month, R and CR rates were higher for OS (86.5% and 75.7%, respectively) and LS groups (93.1% and 89.7%) than Rituximab (46.7% and 30%) (P = 0.0001). Moreover, R rates remained elevated at 60 month for OS and LS groups (83.7% and 89.6% respectively) and 78.4% at 120 month for OS group. CONCLUSION: We observed that splenectomy for ITP second-line treatment was more effective than Rituximab regarding maintenance of R, CR, and overall response rates. OS and LS had similar efficacy.

Gadolinium-based contrast agent toxicity: a review of known and proposed mechanisms.

Gadolinium chelates are widely used as contrast media for magnetic resonance imaging. The approved gadolinium-based contrast agents (GBCAs) have historically been considered safe and well tolerated when used at recommended dosing levels. However, for nearly a decade, an association between GBCA administration and the development of nephrogenic systemic fibrosis (NSF) has been recognized in patients with severe renal impairment. This has led to modifications in clinical practices aimed at reducing the potential and incidence of NSF development. Newer reports have emerged regarding the accumulation of gadolinium in various tissues of patients who do not have renal impairment, including bone, brain, and kidneys. Despite the observations of gadolinium accumulation in tissues regardless of renal function, very limited clinical data regarding the potential for and mechanisms of toxicity is available. This significant gap in knowledge warrants retrospective cohort study efforts, as well as prospective studies that involve gadolinium ion (Gd(3+)) testing in patients exposed to GBCA. This review examines the potential biochemical and molecular basis of gadolinium toxicity, possible clinical significance of gadolinium tissue retention and accumulation, and methods that can limit gadolinium body burden.

Ocular Applications of Dipyridamole: A Review of Indications and Routes of Administration.

Dipyridamole was introduced decades ago as a treatment for angina, subsequently found to inhibit platelet aggregation. It is most commonly used, and approved for use in thromboembolism prevention, following surgery. Some of its recognized effects such as adenosine uptake inhibition, elevation of cAMP and cGMP levels, vasodilation, and tissue perfusion are important in various ocular disorders. For this reason, dipyridamole represents an interesting candidate as a therapeutic target for the treatment of eye disorders affecting different ocular structures. The aim of this article is to review the evidence and current understanding of the mechanisms by which dipyridamole exerts its effects on different ocular tissues, discuss the role of dipyridamole in clinical practice, and highlight areas of use and routes of administration.

Elevated plasma fibrinogen in clinically asymptomatic unicentric Castleman's disease: a case report.

This is the first report of an early association between elevated fibrinogen and asymptomatic unicentric Castleman's disease (CD). A 49-year-old asymptomatic female who was serving as a normal control in an unrelated study was incidentally found to have significantly elevated levels of plasma fibrinogen. Upon further investigation with computer tomography scans and magnetic resonance imaging, the woman was found to have a mobile mass in the abdominal region which was surgically removed. Based on histological analysis, a diagnosis of CD was made. At four-month follow-up, no additional signs of CD were present and fibrinogen levels returned to the normal range. This report, therefore, signifies the importance for physicians to consider unicentric CD in the differential diagnosis when patients present with elevated levels of plasma fibrinogen. Awareness of this diagnostic possibility may lead to increased early diagnosis of CD before symptoms become apparent, and provide a marker candidate for CD activity that may assist in monitoring treatment success.

Pterygium: nonsurgical treatment using topical dipyridamole - a case report.

PURPOSE: We report a case of a symptomatic, inflamed pterygium treated nonsurgically with topical dipyridamole and followed for 12 months. CASE REPORT: A 35-year-old woman presented with a stage II to III, V3, C3, K2, P1 (using Johnston, Williams & Sheppard's classification) pterygium in her right eye. She complained of a foreign body sensation, dryness, burning, and persistent uncontrolled blinking. A raised lesion was observed on the nasal conjunctiva that was 1.5 mm in size. It extended slightly onto the nasal cornea. There was moderate vascularity of the lesion that obscured the underlying scleral vessels. Moderate conjunctival hyperemia was detected at and medial to the pterygium. The cornea, anterior chamber, and external anatomy were otherwise unremarkable. The eye was initially treated twice daily with a topical application of dipyridamole in a normal saline solution, which was later reduced to once daily. RESULTS: There was a marked improvement in both the pterygium and the patient's symptoms. The tissue regressed from the limbal region of the cornea, had decreased in length from 1.5 to 1.0 mm, and decreased in height from approximately 1.0 to approximately 0.3 mm. Conjunctival hyperemia and vascularization resolved completely, and the underlying scleral vessels could once again be visualized. At 12 months, the pterygium was graded as stage 0 to I, V0, C2, K0, P0. CONCLUSIONS: To our knowledge, this is the first case of successful management of a pterygium and associated symptoms using topical dipyridamole. Further investigation is required to clarify the potential role of dipyridamole in the treatment of pterygia and pingueculae.

Rituximab for treating CD20+ prostate cancer with generalized lymphadenopathy: a case report and review of the literature.

A role for CD20 antibodies in treating prostate cancer has not yet been established. We report a case of advanced prostate cancer presenting with generalized lymphadenopathy that expressed CCR7 and CD20. CCR7 expression in prostate cancer has been previously reported only once; the expression of CD20 has not been reported before. Rituximab therapy was initiated in this case and resulted in a significant biochemical response. This unique metastatic and biochemical pattern may signify a distinct subtype of prostate cancer that may be amenable to treatment with anti-CD20 antibodies.

Gastrocele complicates the course of non-operated severe caustic injuries: operative strategies.

BACKGROUND: For selected cases of severe caustic injuries, evidence favors conservative management, consisting of radiographic and clinical observation without emergency surgery. However, this approach can lead to the development of gastric distension caused by combined esophageal and antral strictures, called gastrocele. This study assessed the safety of a two-stage surgical treatment for gastrocele. METHODS: Patients treated in our department between 2004 and 2010 for caustic injury who did not receive emergency surgery and subsequently developed gastrocele were retrospectively analysed. Demographic information, symptoms, and ingestion history were documented. Surgical management included partial gastrectomy and postponed esophageal stricture treatment. Outcome measures included postoperative morbidity and mortality. RESULTS: Eight nonoperated patients with severe caustic injury from suicidal ingestions of caustic substances were found to have developed gastrocoele. They presented with mostly endoscopic stage IIIb esophageal and gastric injuries. All patients had clinical symptoms of vomiting and abdominal tenderness at day 8 after caustic ingestion. Antrectomy and esophageal stricture treatment were performed at an average of 2 and 8 months, respectively, after caustic ingestion. There were no postoperative deaths, and the long-term survival rate was 83 %. CONCLUSIONS: Gastrocele should be suspected in patients with stage III gastric and esophageal injuries who have been treated by conservative management and are still vomiting more than 1 week postingestion. A two-staged surgical strategy of antrectomy followed by a postponed esophageal stricture treatment was found to be safe and effective for these patients.

Opioid growth factor (OGF) for hepatoblastoma: a novel non-toxic treatment.

Hepatoblastoma is the most common liver malignancy in children, typically diagnosed before age 2. The survival rate for hepatoblastoma has increased dramatically in the last 30 years, but the typical chemotherapeutic agents used for treatment are associated with significant toxicity. In this report, the authors present two cases of hepatoblastoma treated with surgical resection and a novel biotherapeutic regimen that included opioid growth factor (OGF). Case #1 is an infant diagnosed with a large mass on prenatal ultrasound. After subsequent diagnosis of hepatoblastoma, she was treated with one course of neoadjuvant chemotherapy at approximately 1 week of age. Following significant complications from the chemotherapy (neutropenic fever, pneumonia and sepsis), the patient's parents declined further chemotherapy, and the infant was treated with surgical resection and opioid growth factor (OGF)/low dose naltrexone (LDN). She is currently at close to 10 years disease-free survival. Case #2 is a child diagnosed with a liver mass on ultrasound at 20 months of age, later biopsy-proven to represent hepatoblastoma. Due to existing co-morbidities including autosomal recessive polycystic kidney disease and hypertension, and indications from the biopsy that the tumor might be insensitive to chemotherapy, the parents elected not to proceed with neoadjuvant chemotherapy. The patient was treated with surgical resection and OGF/LDN, and is currently at more than 5 years disease-free survival. This case series highlights the need for less toxic treatment options than conventional chemotherapy. Modulation of the OGF-OGF receptor axis represents a promising safe and therapeutic avenue for effective treatment of hepatoblastoma.

Therapeutic potential of tranilast, an anti-allergy drug, in proliferative disorders.

Tranilast (N-[3,4-dimethoxycinnamoyl]-anthranilic acid; Rizaben®) is an anti-allergy drug approved for use in Japan and South Korea, also used against asthma, autoimmune diseases, and atopic and fibrotic pathologies. The antitumor potential of tranilast is attracting considerable interest. This review summarizes recent evidence concerning the effect of tranilast on different tumor types and discusses the drug's possible mode of action in this area. In vivo and in vitro studies are covered, as well as evidence from clinical trials, in which tranilast was evaluated in various models of proliferative disorders. The findings presented in this report, demonstrate the excellent potential of tranilast in the management of certain types of tumor, and provide a strong rationale for the initiation of controlled clinical trials in this area.

Intravenous immunoglobulin for the treatment of Crohn's disease.

Crohn's disease (CD) is a debilitating condition which still requires improvement in its management. There is a need for alternatives to anti-tumour necrosis factor drugs which are costly and beneficial in less than 50% of patients. Intravenous immunoglobulin (IVIG) has been used in the management of aminosalicylate- and steroid-resistant CD for more than 20 years, although the published literature available is limited. A literature search identified 17 relevant publications since 1969, including five case reports of single patients, two abstracts, three conference papers, one review paper and six book or journal articles. No randomised controlled trials of IVIG in CD have been published. A review of the evidence identified indicates that IVIG can induce a rapid and significant improvement in aminosalicylate- and steroid-resistant CD, often within days of the initial administration. Data from longer-term studies show that maintenance of remission over the medium term is also possible. These encouraging findings provide a rationale for the initiation of larger randomised controlled trials of IVIG in CD with the aim of providing further treatment options for this difficult-to-manage condition.

The effect of gallium nitrate on arresting blood flow from a wound.

A novel application of gallium nitrate, hitherto unreported, in reducing bleeding time from an open wound is presented. Experiments performed using simple punctures in the forearm demonstrated a very substantial reduction in bleeding time when a solution of gallium nitrate was applied relative to a control. This outcome was shown to be unaffected by the anticoagulant properties of warfarin. The mechanism for such action of gallium nitrate is unknown and merits further investigation, as do the possibilities for such an application to improve both civilian and defense trauma treatment modalities.