Sub-chronic 90-day toxicity of neamine in SD rats and its anti-liver cancer activity in vitro and in vivo.

Neamine, an inhibitor of angiogenin (ANG), is a new investigative anticancer drug currently in preclinical stage. Here we report the 90-day sub-chronic toxicity of neamine in SD rats and its anti-liver cancer activity in vitro and in vivo. Neamine has a No Observed Adverse Effect Level (NOAEL) of 12 and 16mg·kg-1·d-1 for female and male rats, respectively. No mortality was found. The adverse effects included increased organ coefficients of spleen and kidney, increased BUN in both female and male rats at high dose, increased CR and decreased organ coefficients of heart and liver in male rats at high dose. All of which, except the kidney coefficient and BUN in males, returned to normal levels after 28-day recovery. Histopathological examination revealed vacuolar degeneration of glomerulus, degeneration of renal tubules and cast in the kidneys, which were also recovered except in males of high-dosing group. These results indicate that kidney is the most susceptible organ for neamine toxicity. Tissue microarray analysis validated that ANG is up-regulated in hepatocellular carcinoma accompanied by increased nuclear translocation, suggesting that ANG is a possible target for drug development in liver cancer treatment. Neamine blocked nuclear translocation of ANG in HUVEC and HepG2 cells, and inhibited ANG-stimulated cell proliferation without affecting basal level cell proliferation. Neamine also inhibited progression of HepG2 xenografts in athymic mice accompanied by decreased angiogenesis and cancer cell proliferation. These results suggest that neamine is a specific ANG inhibitor with low toxicity and high anti-liver cancer efficacy.

Decolonization of intestinal carriage of extended-spectrum ß-lactamase-producing Enterobacteriaceae with oral colistin and neomycin: a randomized, double-blind, placebo-controlled trial.

OBJECTIVES: Extended-spectrum ß-lactamase-producing Enterobacteriaceae (ESBL-E) are an increasingly frequent cause of infections in the community and the healthcare setting. In this study, we aimed to investigate whether intestinal carriage of ESBL-E can be eradicated. METHODS: We conducted a double-blind, randomized, placebo-controlled, single-centre trial to assess the efficacy of an oral decolonization regimen on intestinal ESBL-E carriage in adult patients with an ESBL-E-positive rectal swab. Fifty-eight patients were allocated 1 : 1 to either placebo or colistin sulphate (50 mg 4×/day) and neomycin sulphate (250 mg 4×/day) for 10 days plus nitrofurantoin (100 mg 3×/day) for 5 days in the presence of ESBL-E bacteriuria. The primary outcome was detection of ESBL-E by rectal swab 28 ± 7 days after the end of treatment. Missing primary outcome data were imputed based on the last available observation. Additional cultures (rectal, inguinal and urine) were taken on day 6 of treatment and on days 1 and 7 post-treatment. The study protocol has been registered with ClinicalTrials.gov (NCT00826670). RESULTS: Among 54 patients (27 in each group) included in the primary analysis, there was no statistically significant difference between the groups with regard to the primary outcome [14/27 (52%) versus 10/27 (37%), P = 0.27]. During treatment and shortly afterwards, there was significantly lower rectal ESBL-E carriage in the treatment group: 9/26 versus 19/22 on day 6 of treatment (P < 0.001) and 8/25 versus 20/26 on day 1 post-treatment (P = 0.001). This effect had disappeared by day 7 post-treatment (18/27 versus 17/25, P = 0.92). Liquid stools were more common in the treatment group (7/27 versus 2/29, P = 0.05). CONCLUSIONS: The regimen used in this study temporarily suppressed ESBL-E carriage, but had no long-term effect.

Aloe vera for treating acute and chronic wounds.

BACKGROUND: Aloe vera is a cactus-like perennial succulent belonging to the Liliaceae Family that is commonly grown in tropical climates. Animal studies have suggested that Aloe vera may help accelerate the wound healing process. OBJECTIVES: To determine the effects of Aloe vera-derived products (for example dressings and topical gels) on the healing of acute wounds (for example lacerations, surgical incisions and burns) and chronic wounds (for example infected wounds, arterial and venous ulcers). SEARCH METHODS: We searched the Cochrane Wounds Group Specialised Register (9 September 2011), the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2011, Issue 3), Ovid MEDLINE (2005 to August Week 5 2011), Ovid MEDLINE (In-Process & Other Non-Indexed Citations 8 September 2011), Ovid EMBASE (2007 to 2010 Week 35), Ovid AMED (1985 to September 2011) and EBSCO CINAHL (1982 to 9 September 2011). We did not apply date or language restrictions. SELECTION CRITERIA: We included all randomised controlled trials that evaluated the effectiveness of Aloe vera, aloe-derived products and a combination of Aloe vera and other dressings as a treatment for acute or chronic wounds. There was no restriction in terms of source, date of publication or language. An objective measure of wound healing (either proportion of completely healed wounds or time to complete healing) was the primary endpoint. DATA COLLECTION AND ANALYSIS: Two review authors independently carried out trial selection, data extraction and risk of bias assessment, checked by a third review author. MAIN RESULTS: Seven trials were eligible for inclusion, comprising a total of 347 participants. Five trials in people with acute wounds evaluated the effects of Aloe vera on burns, haemorrhoidectomy patients and skin biopsies. Aloe vera mucilage did not increase burn healing compared with silver sulfadiazine (risk ratio (RR) 1.41, 95% confidence interval (CI) 0.70 to 2.85). A reduction in healing time with Aloe vera was noted after haemorrhoidectomy (RR 16.33 days, 95% CI 3.46 to 77.15) and there was no difference in the proportion of patients completely healed at follow up after skin biopsies. In people with chronic wounds, one trial found no statistically significant difference in pressure ulcer healing with Aloe vera (RR 0.10, 95% CI -1.59 to 1.79) and in a trial of surgical wounds healing by secondary intention Aloe vera significantly delayed healing (mean difference 30 days, 95% CI 7.59 to 52.41). Clinical heterogeneity precluded meta-analysis. The poor quality of the included trials indicates that the trial results must be viewed with extreme caution as they have a high risk of bias. AUTHORS' CONCLUSIONS: There is currently an absence of high quality clinical trial evidence to support the use of Aloe vera topical agents or Aloe vera dressings as treatments for acute and chronic wounds.

Anterior cervical discectomy, drainage and non-instrumented cortico-cancellous allograft fusion: a treatment option for ventral cervical spinal epidural abscess.

INTRODUCTION: Ventral cervical spinal epidural abscess is a very rare clinical condition with a relatively high morbidity and mortality. Due to the paucity of reported cases there is heterogeneity and no clear "gold standard" in the treatment of these patients. OBJECTIVE: The authors report four consecutive patients with ventral cervical spinal epidural abscess treated with anterior cervical discectomy, abscess drainage and original non-instrumented cortico-cancellous allograft spinal fusion. METHODS: The authors retrospectively reviewed a series of four patients treated for ventral cervical epidural spinal abscess. All patients were treated with an urgent operation. Anterior cervical discectomy, abscess drainage, and non-instrumented cortico-cancellous allograft spinal fusion followed by cervical immobilization and systemic antibiotic treatment were utilized. RESULTS: The bone fusion occurred within a mean of 3.5 months of follow-up. No significant radiologic or clinical evidence of graft subsidence was noted after a minimum of 2.5 years follow-up. All patients resolved infection and were neurologically intact. No complications of treatment were noted. CONCLUSION: Urgent operative treatment with anterior cervical discectomy, abscess drainage and non-instrumented cortico-cancellous allograft spinal fusion, followed by immobilization and the appropriate systemic antibiotic treatment is an effective original modification for the treatment and resolution of ventral cervical epidural spinal abscess.

Antimicrobial Activity of a Triple Antibiotic Combination Toward Ocular Pseudomonas aeruginosa Clinical Isolates.

Purpose: Pseudomonas aeruginosa is a leading cause of corneal infections. Recently, we discovered an antimicrobial drug combination, polymyxin B/trimethoprim (PT) + rifampin, that displayed impressive efficacy toward P. aeruginosa in both in vitro and in vivo studies. As such, this combination was further evaluated as a potential keratitis therapeutic through testing the combination's efficacy against a diverse set of P. aeruginosa clinical isolates. Methods: Minimum inhibitory concentrations (MICs) of moxifloxacin, levofloxacin, erythromycin, tobramycin, PT, polymyxin B (alone), trimethoprim (alone), and rifampin were determined for 154 ocular clinical P. aeruginosa isolates, 90% of which were derived from corneal scrapings. Additionally, the efficacy of PT + rifampin was evaluated utilizing fractional inhibitory concentration (FIC) testing. Results: While 100% of isolates were resistant to erythromycin (average MIC 224 ± 110 µg·mL-1) and trimethoprim (alone) (206 ± 67.3 µg·mL-1), antibiotic resistance was generally found to be low: moxifloxacin (2% of isolates resistant; average MIC 1.08 ± 1.61 µg·mL-1), levofloxacin (3.9%; 1.02 ± 2.96 µg·mL-1), tobramycin (1%; 0.319 ± 1.31 µg·mL-1), polymyxin B (0%; 0.539 ± 0.206 µg·mL-1), PT (0%; 0.416 ± 0.135 µg·mL-1), and rifampin (0%; 23.4 ± 6.86 µg·mL-1). Additionally, FIC testing revealed that PT + rifampin eradicated 100% of isolates demonstrating additive or synergistic activity in 95% of isolates (average FIC index 0.701 ± 0.132). Conclusions: The drug combination of PT + rifampin was effective against a large panel of clinically relevant P. aeruginosa strains and, as such, may represent a promising therapeutic for P. aeruginosa keratitis. Translational Relevance: This work furthers the preclinical development of a novel antibiotic combination for the treatment of corneal infections (bacterial keratitis).

Topical ciprofloxin versus topical framycetin-gramicidin-dexamethasone in Australian aboriginal children with recently treated chronic suppurative otitis media: a randomized controlled trial.

BACKGROUND: Chronic suppurative otitis media (CSOM) affects many children in disadvantaged populations. The most appropriate topical antibiotic treatment in children with persistent disease is unclear. METHODS: Children with CSOM despite standard topical treatment were randomized to 6-8 weeks of topical ciprofloxacin (CIP) versus topical framycetin-gramicidin-dexamethasone (FGD). Otoscopic, audiologic, and microbiologic outcomes were measured using standardized assessments and blinding. RESULTS: Ninety-seven children were randomized. Ear discharge failed to resolve at the end of therapy in 70% children regardless of allocation [risk difference = -2%; (95% CI: -20 to 16)]. Healing of the tympanic membrane occurred in one of 50 children in the CIP group and none of 47 children in the FGD group. Severity of discharge failed to improve in more than 50% children in each group, and mean hearing threshold (38 dB and 35 dB) and proportion of children with greater than 25 dB hearing loss (98% and 88%) were not significantly different between the CIP and FGD groups. Side effects were rare. CONCLUSIONS: This study showed a similarly low rate of improvement or cure in children with persistent CSOM for both CIP and FGD topical therapies. Complications and side effects were insufficient to cease therapy or inform prescribing of either therapy.

Neamine inhibits xenografic human tumor growth and angiogenesis in athymic mice.

PURPOSE: We have previously shown that the aminoglycoside antibiotic neomycin blocks the nuclear translocation of angiogenin and inhibits its angiogenic activity. However, neomycin has not been considered as a favorable drug candidate for clinical development because of its known nephrotoxicity and ototoxicity. The aim of this study is to determine whether neamine, a nontoxic derivative of neomycin, possesses antitumor activity. EXPERIMENTAL DESIGN: The effect of neamine on the nuclear translocation of angiogenin was examined by means of immunofluorescence and Western blotting. The antitumor activity of neamine was determined with three different animal models. RESULTS: Neamine effectively blocked the nuclear translocation of angiogenin in endothelial cells and inhibited angiogenin-induced cell proliferation. It inhibited the establishment of human tumor xenografts in athymic mice in both ectopic and orthotopic tumor models. It also inhibited the progression of established human tumor transplants, whereas the structurally related antibiotic paromomycin had no effect. Immunohistochemical staining showed that both angiogenesis and cancer cell proliferation are inhibited by neamine. CONCLUSION: These results suggest that the nontoxic aminoglycoside antibiotic neamine is an effective inhibitor of nuclear translocation of angiogenin and may serve as an inhibitor for angiogenin-induced angiogenesis and cancer progression.

Multidisciplinary care of a paediatric patient with Gradenigo's syndrome.

A 10-year-old girl presented with signs and symptoms suggestive of Gradenigo's syndrome, a condition characterised by otorrhoea, diplopia due to abducens nerve palsy and pain in the region of the trigeminal nerve. This case examines the presentation of this condition, and the appropriate investigations. We also highlight the importance of the involvement of multiple specialities in discussing and devising a suitable management plan.

Neamine inhibits growth of pancreatic cancer cells in vitro and in vivo.

Neamine, a non-toxic derivative of neomycin, has recently been shown to have antitumor activities in various types of cancers. However, its effect on pancreatic cancer is still unknown. The study aimed to investigate its antitumor activity on pancreatic cancer and the underlying mechanisms. MTT assay was used to observe the effect of neamine on angiogenin (ANG)-induced AsPC-1 cell proliferation. Tissue microassay and immunofluorescence staining were used to detect the expression of ANG and its nuclear translocation, respectively. Tumor xenografts were established by subcutaneous inoculation of AsPC-1 pancreatic cancer cells into the right flanks of nude mice, and neamine was injected subcutaneously. Immunohistochemistry was done to observe the expression of ANG, CD31 and Ki-67 in tumor xenografts. It was found that neamine blocked the nuclear translocation of ANG effectively and inhibited ANG-induced AsPC-1 cell proliferation in a dose-dependent manner. Neamine had anti-tumor effects on AsPC-1 xenograft models. Consistently, neamine reduced the expression levels of ANG, Ki-67 and CD31 in tumor xenografts. It was concluded that neamine may be a promising agent for treatment of pancreatic cancer.

Prescription pattern for treatment of hemorrhoids under the universal coverage policy of Thailand.

The Universal Coverage Policy (UCP) or "30 Baht Scheme" was launched in Thailand in 2001. The policy caused a cutback in the budgets of all public hospitals and health service centers. Traditional medicine was then viewed as an alternative to save costs. This study examines whether this had any influence on hemorrhoid treatment prescription patterns, ratio of traditional/modern medicine, or the cost of hemorrhoid treatment after the UCP was implemented at a community hospital. The traditional medicine prescribed was Petch Sang Kart and the modern alternative was Proctosedyl. All hemorrhoid prescriptions at a community hospital from October 2000 to January 2003 were surveyed. Segmented Regression Analysis was applied to evaluate prescription trends, the ratios between the types of medicine, and the hemorrhoid treatment cost. A total of 256 prescriptions were analyzed. The average number of traditional medicine prescriptions per month were more than modern medicine (41 versus 16). During the study period, the trend of modern medicine use and the treatment cost was decreased (p < 0.01). The ratio of traditional/modern medicine increased 0.2 times (p = 0.02).

Antibacterial Drugs today: II.

Since the development of the sulphonamides in the 1930s and the subsequent development of antibiotics from the 1940s onwards, there have now been many drugs developed which are capable of chemotherapeutic activity in a patient infected by a susceptible micro-organism. This review is concerned with precise descriptions of important groups of antimicrobial drugs, with emphasis being placed on the more recently developed drugs. With each group of drugs the pharmacology, major therapeutic indications, dosages and adverse reactions are discussed. Part II of the review discusses the cephalosporins, polymyxins and aminoglycosides. The place of each in therapy is defined.

Tularemia of the middle ear.

We report the case of a 10-year-old boy with prolonged fever who was found to have tularemia of the middle ear. Otolaryngologic cases including oropharyngeal and glandular or ulceroglandular forms of the head and neck region are estimated to account for 12% of all tularemia cases, but to date we have not seen a report of tularemia in the middle ear. The possibility of tularemia may not occur to a physician because of the wide variation of clinical manifestations.

A general practice study to compare the efficacy and tolerability of a spray ('Otomize') versus a standard drop formulation ('Sofradex') in the treatment of patients with otitis externa.

In an open, multi-centre study in general practice, a comparison was made of the efficacy, tolerability and acceptability of a neomycin/dexamethasone preparation administered by metered-dose spray ('Otomize') and a framycetin/gramicidin/dexamethasone preparation ('Sofradex') administered as drops in 60 patients with otitis externa. Patients were allocated at random to receive one or other preparations 3-times daily for 10 days and were followed-up again 14 days after cessation of therapy. Clinical assessments were carried out under observer blind conditions on entry (Day 0) and on Days 10 and 24 of the severity of erythema, swelling and debris in the affected ear(s). A global assessment of clinical outcome was made by the doctor on Day 10. There were no significant differences in the two groups at the start of treatment. Significant improvement occurred in both groups from Day 0 to Day 10 and from Day 10 to Day 24 in all symptoms, with the proportion symptom-free in the 'Otomize' group significantly greater than in the 'Sofradex' group at 24 days, and approaching significance at 10 days. Significantly more patients in the 'Otomize' group were rated as having a good clinical outcome by the physician, and fewer patients experienced discomfort on application. Few side-effects were reported by either treatment group, none necessitating discontinuation of therapy.

Comparative efficacy and tolerability of two ointment and suppository preparations ('Uniroid' and 'Proctosedyl') in the treatment of second degree haemorrhoids in general practice.

A multi-centre general practice, open study was carried out in 89 patients with second degree haemorrhoids to compare the efficacy and tolerability of two antibiotic-corticosteroid combinations ('Uniroid' and 'Proctosedyl') in ointment and suppository formulations. Patients were allocated at random into 4 groups and received treatment with one of the trial preparations for 1, 2 or 3 weeks, as required, with weekly assessments of response. There were no significant differences between the various groups at the start of treatment. Significant improvement occurred in all groups during treatment. Both suppository and ointment formulations were broadly comparable and control of symptoms was achieved from Week 2 onwards, building up to levels in excess of 90% after 3 weeks of therapy. With regard to the symptoms of pain and itching, suppositories gave marginally greater relief in the early stages of treatment, while both ointment and suppositories were associated with similar reduction in bleeding from haemorrhoids. Whereas both suppository formulations were about equal in reducing anal discharge, 'Uniroid' ointment was clinically superior to 'Proctosedyl' ointment in controlling this symptom over the 3-week trial period. No unwanted effects were experienced attributable to treatment. No statistically significant differences between the two ointment and the two suppository formulations were identified in this study and all four preparations were found to be efficacious in the majority of patients studied.

Joint-ill and other bacterial infections on thoroughbred studs.

From a perinatal survey carried out on Thoroughbred studs, information was obtained on the incidence, mortality and long-term effects of joint-ill and other bacterial infections. Many of these infections occurred in foals with a history of other perinatal abnormalities, and in foals in which receipt of colostrum was delayed. There was no direct relationship between the incidence of infection and maternal age, but prenatal lactation and loss of colostrum were more frequent in older mares. There was a significant reduction in the incidence of infections in foals given neomycin and framomycin during the first 30 days of life.

Contact allergy to various components of topical preparations for treatment of external otitis.

Patients suffering from chronic external otitis had developed contact allergies to one or more compounds of topical preparations in 40% of 142 tested patients. Neomycin and framycetin caused most of the allergic reactions (16.2%) followed by chinoform (7.0%), chloramphenicol and polymyxin (4.2%). Preservatives of the topical otic preparations such as benzethonium chloride (8.5%), benzalkonium chloride (6.3%) and thimerosal (merthiolate) (5.6%) were also common causes of allergic reactions. An epicutaneous test (patch test) using compounds in topical preparations should be done in cases of prolonged, treatment resistant external otitis.

Myringoplasty (A review of 365 operations).

A series of 365 cases of tympanic membrane repair by the same surgeon is analysed, comparing the results of different techniques and grafting materials. A detailed study of 206 of these cases employing the underlay technique with temporal fascia is reported. In this group a graft take rate of 91.4 per cent in dry ears, and of 89.3 per cent in all cases, was achieved. Various factors liable to influence the success rate are analysed and discussed. No cases of conductive or sensori-neural hearing loss resulting from the operation were encountered.

Ventilation tubes, swimming and otorrhoea: a New Zealand perspective.

OBJECTS: To compare advice given by specialist otolaryngologists to patients following ventilation tube insertion and the management of purulent otorrhoea in these patients. METHODS: A postal questionnaire was sent to all 59 specialists currently listed in the New Zealand Otolaryngology Specialist Register. RESULTS: 96.5% of specialist otolaryngologists replied, 88% in sufficient detail for analysis in this study. The vast majority (96%) allowed patients to swim with tubes in situ, and all allowed hair washing. Advice for ear protection varied. If otorrhoea develops with ventilation tubes in situ, 90% of specialists advise patients to stop swimming, but allow hair washing to continue with ear protection. Ninety percent of specialists' initial treatment of otorrhoea involves a combination of suction toilet and topical steroid/antibiotic drops. CONCLUSION: In general, specialist otolaryngologists in New Zealand give similar advice to patients with ventilation tubes. However, the specific methods of ear protection advised when swimming and hair washing varies markedly.