Inhibition of murine hepatitis virus infections by the immunomodulator 2,3,5,6,7,8-hexahydro-2-phenyl-8,8-dimethoxy-imidazo[1,2a]pyridine (PR-879-317A).

PR-879-317A (2,3,5,6,7,8-hexahydro-2-phenyl-8,8-dimethoxy-imidazo [1,2a]pyridine) has been found to be a T-cell-selective immunomodulating agent. In the current studies, a series of experiments was designed to determine the potential antiviral activity of this compound in mice infected with murine hepatitis virus. In a comparative antiviral experiment, the activity seen was superior to that of levamisole, a known immunorestorative agent. This activity was characterized by an increase in the 21-day survival frequency, a decrease in hepatic discoloration, a decrease in the amount of infectious virus recoverable from the liver, and normalization of serum glutamic oxalacetate and pyruvate transaminase levels. A comparison of treatment routes indicated the relative efficacies as intraperitoneal greater than per os greater than intramuscular greater than or equal to subcutaneous. Alteration of the treatment schedule markedly affected the antiviral effect; prophylactic or therapeutic treatments once or twice daily for 3 days were usually effective. Single treatments begun 4 h before or 24 h after virus inoculation were highly efficacious. Three treatments administered on alternate days, beginning 48 h before virus inoculation, proved moderately effective. Thrice-daily treatments were ineffective, as were treatments with durations of greater than 3 days. The optimal dosage varied according to the treatment route and dosage schedule. When assessed for direct antiviral activity in vitro, PR-879-317A failed to demonstrate any significant activity against murine hepatitis virus. The positive in vivo activity noted might therefore be the result of immune modulation rather than a direct antiviral effect.     

Safety and efficacy of topical norfloxacin versus tobramycin in the treatment of external ocular infections.

Bacterial conjunctivitis appears to resolve more rapidly when treated with appropriate topical antimicrobial agents. In this multicenter, randomized, double-blind study of efficacy and safety, patients with presumed bacterial external eye infections were assigned to topical therapy with 0.3% norfloxacin or 0.3% tobramycin. A total of 120 patients were enrolled. Of the total, 65 had documented bacterial infections and were evaluable; 59 of these patients had bacterial conjunctivitis. All of the patients with documented infections were cured or improved regardless of the drug treatment regimen or in vitro susceptibility testing results. The most common bacteria isolated were Haemophilus influenzae, Streptococcus pneumoniae, alpha-hemolytic streptococci, Staphylococcus aureus, and Staphylococcus sp. No patients had serious adverse reactions attributed to their therapy. Norfloxacin ophthalmic solution seems to be a safe, effective, and appropriate agent for the treatment of bacterial external eye infections.     

Effect of cyclosporin a on proteinuria in patients with Alport's syndrome

Eight patients with Alport's syndrome and massive proteinuria (129±60.57 mg/m² per hour) were treated with cyclosporin A (CyA) for 8 months. The average dose of CyA administered to all patients was 4.21±0.26 mg/kg per day and blood CyA levels of 63.4±4.1 ng/ml were attained. In five patients, proteinuria abated during the 3rd week of treatment. In the remaining three, all of whom had low creatinine clearance (82.0, 46.0 and 43.2 ml/min per 1.73 m² respectively), proteinuria persisted but at levels lower than before treatment: 32.5±15.9 mg/m² per hour versus 183.3±29.7 mg/m² per hour. No permanent decrease in creatinine clearance was observed in any of these patients throughout treatment. In those patients in whom proteinuria abated, it reappeared 2 weeks after discontinuation of CyA treatment. We observed no significant increases in angiotensin II plasma levels in our patients during CyA administration. Although we have shown that CyA will reduce massive proteinuria in patients with Alport's syndrome, we cannot yet recommend its use as a therapeutic measure.     

Immunopathologic alterations in murine models of sepsis of increasing severity

We investigated inflammatory and physiologic parameters in sepsis models of increasing lethality induced by cecal ligation and puncture (CLP). Mice received imipenem for antibiotic therapy, and groups were sacrificed at 2, 4, 8, 12, 16, 20, and 24 h after CLP. The severity of sepsis increased with needle puncture size (lethality with 18-gauge puncture [18G], 100%; 21G, 50%; 25G, 5%; sham treatment, 0%). While the temperature (at 12 h) and the activity and diurnal rhythm (at day 4) of the 25G-treated CLP group recovered to normal, the 21G and 18G treatment groups exhibited severe hypothermia along with decreased activities. A direct correlation was also observed between the severity of sepsis and cytokine (interleukin 1beta [IL-1beta], tumor necrosis factor [TNF], IL-6, and IL-10) concentrations in both the peritoneum and the plasma. There were substantially higher cytokine levels in the more severe CLP models than in the sham-treated one. Peritoneal and plasma TNF levels were always less than 40 pg/ml in all models. None of the cytokines in the septic mice peaked within the first hour, which is in contrast to the results of most endotoxin models. Chemokine (KC and macrophage inflammatory protein 2) profiles also correlated with the severity of sepsis. Except for the chemokines, levels of inflammatory mediators were always higher at the site of inflammation (peritoneum) than in the circulation. Our study demonstrated that sepsis of increasing severity induced increased cytokine levels both within the local environment (peritoneum) and systemically (plasma), which in turn correlated with morbidity and mortality.     

Randomized, double-blind, placebo-controlled study of montelukast for treating perennial allergic rhinitis.

BACKGROUND: Perennial allergic rhinitis (PAR) is a persistent allergic inflammation of the upper respiratory tract due to year-round allergen exposure. OBJECTIVE: To evaluate the leukotriene receptor antagonist montelukast for the treatment of PAR. METHODS: Protocol 265 was a 2-arm study performed during the winter. After a placebo run-in period, adults with perennial allergen sensitivity and active symptoms of PAR were randomized to receive 10 mg of montelukast (n=1002) or placebo (n=990) once daily during a 6-week, double-blind, active-treatment period. The primary end point was the daytime nasal symptoms score, defined as the average of scores for nasal congestion, rhinorrhea, and sneezing rated daily by patients. RESULTS: Statistically significant improvements in PAR symptoms were seen in patients treated with montelukast. Their daytime nasal symptoms scores were reduced during treatment compared with those of the placebo group: the difference between treatments in least squares mean change from baseline was -0.08 (95% confidence interval [CI], -0.12 to -0.04; P < .001). Montelukast treatment also improved global evaluations of allergic rhinitis by patients and Rhinoconjunctivitis Quality of Life Questionnaire scores: differences vs the placebo group were -0.15 (95% CI, -0.27 to -0.04; P < .01) and -0.15 (95% CI, -0.24 to -0.06; P < .001), respectively. Other end points that showed statistically significant improvement with montelukast treatment were nighttime symptoms and each of the 4 nasal symptoms (congestion, rhinorrhea, sneezing, and itching). The treatment effects of montelukast were stable and persistent during the entire 6 weeks of treatment. CONCLUSION: Montelukast provided statistically significant relief of PAR symptoms during 6 weeks of treatment.     

The sorptivity and durability of gelling fibre dressings tested in a simulated sacral pressure ulcer system

Wound‐dressing performances are affected by exudate viscosity, resistance to flow because of gravity, and bodyweight loads, the level of which is related to the body position. Here, we focussed on two dressing properties: (a) Sorptivity—the ability of dressings to transfer exudate away from the wound bed by capillary action—and (b) Durability—the capacity of dressings to maintain their integrity over time and during their removal. Both properties are critically important for avoiding further tissue damage but require the development of new laboratory tests for their measurement. A computer‐controlled phantom of an exuding sacral pressure ulcer has therefore been developed and used to compare the performances of Exufiber (Mölnlycke Health Care) vs an alternative market‐leading dressing. Sorptivity was determined using weight tests, and durability was measured through tensile tests of the used dressings. For a supine configuration, the Exufiber dressing demonstrated ~three times higher sorptivity and better durability, withstanding ~five times greater strain energy than the other product before failure occurred. This work paves the way for quantitative, standardised testing of dressings in all aspects of exudate management. The reported tests are further suitable for testing dressing combinations or how dressings interact with negative pressure wound therapy.     

Transthoracic 2D echo color Doppler assessment of internal mammary artery to left anterior descending coronary artery graft

For noninvasive evaluation of anatomy and flow characteristics of internal mammary artery graft (IMA-graft), 2D echo-Color-Doppler (CDE) was performed in 60 patients (54 M, 6 F, mean age 54.1±6.9 y), who underwent coronary angiography 20.1 ±13 months after a coronary artery bypass graft (CABG).CDE was performed, using an echocardiographic unit equipped with a 5 MHz linear transducer.In all patients, measurements of IMA-graft diameter (mm), and peak systolic and diastolic flow velocity (cm/sec) were obtained at baseline and also in 16 patients after dipyridamole infusion (0.54 mg/Kg/min) and in 10 patients after sublingual nitroglycerin (NTG) (0.4 mg). Angiography showed the IMA-graft patency in 58/60 patients (96.8%).A typical biphasic flow was displayed by CDE in 49/58 patients (84.4%) with angiographic patency.Dipyridamole infusion increased both IMA-graft diameter and peak diastolic flow velocity (PDFV) from 2.28 ±0.51mm to 2.9 ±0.42mm and from 19.4 ±6.2 cm/sec to 93.9 ±29 cm/sec, respectively (p<0.0001).No significant modifications of peak systolic flow velocity (PSFV) were observed.NTG increased PDFV from 29.11 ±8 cm/sec to 41.88 ±7.20 cm/sec (p<0.005), while diameter and PSFV showed no statistically significant modifications.CDE is a useful diagnostic tool for noninvasive evaluation of IMA-graft patency both early after surgery and during long-term follow-up. CDE pharmacological stress improves the sensibility of the technique and it can provide indirect information about pathophysiology of recipient coronary vessel.     

Fatal meningoencephalitis due to Bacillus anthracis

Abstract: We report the first case of fatal anthrax meningoencephalitis in Hong Kong over the past 60 years. A 13 year-old boy presented with right lower quadrant pain, diarrhoea and progressive headache. Lumbar puncture yielded gram positive bacilli initially thought to be Bacillus cereus, a contaminant. He was treated with ampicillin and cefotaxime, but died 3 days after hospitalization. The organism isolated from blood and cerebrospinal fluid was later identified as Bacillus anthracis.