Identification, Virulence, and Distribution of Two Biovars of Pseudomonas syringae pv. actinidiae in New Zealand.

Pseudomonas syringae pv. actinidiae, the causal agent of bacterial canker of kiwifruit, was detected for the first time in New Zealand in November 2010. Only in Bay of Plenty, one of the four regions where this pathogen had been detected, did symptoms evolve beyond leaf spots, resulting in cane die-back, wilting of canes, and canker, sometimes leading to death of the vine. Molecular analysis (cts haplotype and BOX-polymerase chain reaction [PCR] electrophoretic pattern) of strains isolated from different regions of New Zealand revealed that two biovars could be distinguished. They have been called biovar 3 and biovar 4 to differentiate them from strains from Japan (biovar 1) or Korea (biovar 2), which have a different cts haplotype or a different BOX-PCR pattern. Biovars 3 and 4 displayed different degrees of virulence, as measured by their ability to cause leaf spots on young, potted kiwifruit plants. Biovar 3, which has also been present in Italy since 2008 and in France, was found in the Bay of Plenty, where cane diebacks were observed. In contrast, no symptoms other than leaf spots have been observed in orchards where strains of biovar 4 have been isolated. We report the distribution and the disease progression of biovars 3 and 4 in New Zealand.

Oxidized-LDL enhances coronary vasoconstriction by increasing the activity of protein kinase C isoforms alpha and epsilon.

Oxidized low-density lipoprotein (ox-LDL) plays a critical role in the development of atherosclerotic coronary vasospasm; however, the cellular mechanisms involved are not fully understood. We tested the hypothesis that ox-LDL enhances coronary vasoconstriction by increasing the activity of specific protein kinase C (PKC) isoforms in coronary smooth muscle. Active stress was measured in de-endothelialized porcine coronary artery strips; cell contraction and [Ca(2+)](i) were monitored in single coronary smooth muscle cells loaded with fura-2; and the cytosolic and particulate fractions were examined for PKC activity and reactivity with isoform-specific anti-PKC antibodies with Western blots. Ox-LDL (100 microgram/mL) caused slow but significant increases in active stress to 1.3+/-0.4x10(3) N/m(2) and cell contraction (10%) that were completely inhibited by GF109203X (10(-6) mol/L), an inhibitor of Ca(2+)-dependent and -independent PKC isoforms, with no significant change in [Ca(2+)](i). 5-Hydroxytryptamine (5-HT; 10(-7) mol/L) and KCl (24 mmol/L) caused increases in cell contraction and [Ca(2+)](i) that were inhibited by the Ca(2+) channel blocker verapamil (10(-6) mol/L). Ox-LDL enhanced coronary contraction to 5-HT and KCl with no additional increases in [Ca(2+)](i). Direct activation of PKC by phorbol 12-myristate13-acetate (PMA; 10(-7) mol/L) caused a contraction similar in magnitude and time course to ox-LDL-induced contraction and enhanced 5-HT- and KCl-induced contraction with no additional increases in [Ca(2+)](i). The ox-LDL-induced enhancement of 5-HT and KCl contraction was inhibited by Gö6976 (10(-6) mol/L), an inhibitor of Ca(2+)-dependent PKC isoforms. Both ox-LDL and PMA caused an increase in PKC activity in the particulate fraction, a decrease in the cytosolic fraction, and an increase in the particulate/cytosolic PKC activity ratio. Western blots revealed the Ca(2+)-dependent PKC-alpha and the Ca(2+)-independent PKC-delta, -epsilon, and -zeta isoforms. In unstimulated tissues, PKC-alpha- and -epsilon were mainly cytosolic, PKC-delta was mainly in the particulate fraction, and PKC-zeta was equally distributed in the cytosolic and particulate fractions. Ox-LDL alone or PMA alone caused translocation of PKC-epsilon from the cytosolic to particulate fraction, whereas the distribution pattern of PKC-alpha, -delta, and -zeta remained unchanged. 5-HT (10(-7) mol/L) alone and KCl alone did not change PKC activity. In tissues pretreated with ox-LDL or PMA, 5-HT and KCl caused additional increases in PKC-alpha activity. Native LDL did not significantly affect coronary contraction, [Ca(2+)](i), or PKC activity. These results suggest that ox-LDL causes coronary contraction via activation of the Ca(2+)-independent PKC-epsilon and enhances the contraction to [Ca(2+)](i)-increasing agonists by activating the Ca(2+)-dependent PKC-alpha. Activation of PKC-alpha and -epsilon may represent a possible cellular mechanism by which ox-LDL could enhance coronary vasospasm.

Mometasone furoate 0.1%-salicylic acid 5% ointment versus mometasone furoate 0.1% ointment in the treatment of moderate-to-severe psoriasis: a multicenter study.

Topical corticosteroids and keratolytics are both used widely in the management of patients with psoriasis. A combination of the two types of agents may provide enhanced relief. The purpose of this study was to compare the efficacy and safety of the combination ointment mometasone furoate 0.1% plus salicylic acid 5% with that of mometasone furoate 0.1% ointment in the treatment of moderate-to-severe psoriasis vulgaris. A total of 408 patients were enrolled in this controlled, randomized, double-masked, parallel-group, multicenter comparison. Patients applied either mometasone furoate-salicylic acid ointment or mometasone furoate ointment alone to target lesions twice daily for 21 days. Severity of erythema, induration, and scaling were scored at baseline and at days 4, 8, 15, and 22. An evaluation of overall change in disease status of all treated lesions was performed at each follow-up visit. Adverse events were also monitored and scored, including signs of skin atrophy. Beginning on day 8, the combination of mometasone furoate-salicylic acid was significantly more effective than mometasone furoate alone, as indicated by the mean percentage of improvement in total disease scores, mean total disease sign scores, and the individual score for scaling. Similarly, the combination was more effective beginning on day 15, as indicated by the global evaluation of overall clinical response and individual scores for erythema and induration. Both treatments were well tolerated. Mometasone furoate-salicylic acid ointment provides more effective treatment of moderate-to-severe psoriasis than does mometasone furoate ointment alone and is safe and well tolerated.

Mometasone furoate 0.1%-salicylic acid 5% ointment twice daily versus fluocinonide 0.05% ointment twice daily in the management of patients with psoriasis.

This study compared the clinical efficacy and safety of the combination agent mometasone furoate 0.1%-salicylic acid 5% ointment with those of the single agent fluocinonide 0.05% ointment, each applied twice daily for 21 days, in the treatment of patients with moderate to severe plaque psoriasis. Forty adult patients were included in this single-center, randomized, double-masked, intraindividual, bilateral-paired comparative trial. Two similar, bilaterally symmetrical target lesions on the trunk, arms, or legs of each patient were selected for treatment and evaluation. One lesion was treated with mometasone furoate 0.1%-salicylic acid 5% ointment, and the other was treated with fluocinonide 0.05% ointment, both twice daily for 21 days. Treatment was randomly assigned to the right or left side of the body. Signs of psoriasis (ie, erythema, induration, and scaling) and overall clinical response were evaluated and scored on days 4, 8, 15, and 22 and compared against baseline. Patients were asked to evaluate the treatments for efficacy and acceptability at each visit. The primary efficacy parameter was the mean percentage of improvement in total sign scores for the target lesions. Safety was evaluated based on clinical observation and patients' reports. Beginning with day 15, statistically significant differences favoring mometasone furoate 0.1%-salicylic acid 5% ointment over fluocinonide 0.05% ointment were seen in individual and total sign scores, as well as in overall global clinical response. On day 15, 20 patients expressed a preference for one treatment over the other, and 20 patients made no distinction between the two. Of those who expressed a preference, significantly more patients believed mometasone furoate 0.1%-salicylic acid 5% ointment to be better than fluocinonide 0.05% ointment. On day 22, of 25 patients who expressed a preference, significantly more patients thought mometasone furoate 0.1%-salicylic acid 5% ointment was better than fluocinonide 0.05% ointment. No adverse events were recorded for either treatment group. The combination mometasone furoate 0.1%-salicylic acid 5% ointment was significantly more efficacious than and equally as safe as fluocinonide 0.05% ointment in the management of patients with plaque psoriasis and was preferred by a greater number of patients.

Treatment of cutaneous squamous cell carcinomas by intralesional interferon alfa-2b therapy.

BACKGROUND AND DESIGN: Intralesional recombinant interferon alfa-2b has been shown to be effective in the treatment of actinic keratoses and basal cell carcinomas. This open-label study was designed to evaluate the effectiveness and cosmetic result of this therapy on actinically induced, primary cutaneous squamous cell carcinomas. Thirty-six squamous cell carcinomas (28 invasive lesions and 8 in situ lesions) ranging in size from 0.5 to 2.0 cm in the longest dimension were treated with interferon alfa-2b 1.5 million units injected intralesionally three times per week for 3 weeks. Eighteen weeks following therapy, the treatment sites were excised and examined for histologic evidence of remaining tumor. RESULTS: Thirty-three (97.1%) of 34 evaluable lesions revealed an absence of squamous cell carcinoma histologically after therapy, although three biopsy specimens (8.8%) obtained after treatment showed actinic keratoses, for an overall complete response rate of 88.2%. The lesion not eliminated after treatment was an invasive squamous cell carcinoma. The investigators and patients independently judged 93.9% of cases to have a very good or excellent cosmetic result. Adverse reactions were limited to those influenzalike symptoms well recognized to occur with interferon therapy and these were well tolerated. Only one patient discontinued therapy due to side effects. CONCLUSIONS: This trial demonstrates that intralesional interferon is effective in the treatment of small sun-induced squamous cell carcinomas with well-tolerated side effects and a highly acceptable cosmetic result.

Intralesional interferon therapy for basal cell carcinoma.

In a clinical trial of 172 patients at four medical centers, interferon alfa-2b (1.5 x 10(6) IU) or a placebo was injected directly into biopsy-proved noduloulcerative or superficial basal cell carcinomas three times weekly for 3 weeks, for a cumulative dose of 13.5 million IU. Efficacy of treatment was determined at 16 to 20 weeks by examination of biopsy specimens that demonstrated cure of lesions in 86% of interferon-treated patients and in only 29% of placebo-treated patients. During the treatment course and follow-up, an initial inflammatory response was observed at the treatment sites, followed by diminished erythema, improvement in overall appearance, and a decrease in size of lesions. Side effects of treatment, mainly flu-like symptoms, were usually mild and transient and occurred more commonly in the interferon-treated group. Only three patients, all in the interferon-treated group, discontinued therapy because of side effects. One year after initiation of therapy, 81% of interferon recipients and 20% of those given the placebo remained tumor free. Noduloulcerative and superficial lesions were equally responsive to treatment with interferon. For some patients with noduloulcerative or superficial basal cell carcinomas, intralesional interferon alfa-2b may be an alternative, effective treatment.

The effect of an intralesional sustained-release formulation of interferon alfa-2b on basal cell carcinomas.

Intralesional interferon alfa-2b has been proven effective in the treatment of basal cell carcinomas. Because nine injections over a 3-week period have been necessary to produce clinically significant cure rates, a sustained-release protamine zinc chelate interferon formulation has been developed. In this study, 65 basal cell carcinomas were treated in one of two dosing schedules with intralesional sustained release interferon alfa-2b (10 million IU per injection). Thirty-three patients received a single injection and 32 patients received one injection per week for 3 weeks. At study week 16, 80% of evaluable tumors treated with three injections and 52% treated with one injection were cured histologically. Two patients discontinued injections because of side effects. A sustained-release protamine zinc preparation of interferon alfa-2b shows promise as a practical, effective, and cosmetically elegant treatment for basal cell carcinoma.

Treatment of basal cell carcinoma with intralesional interferon.

Eight patients with basal cell carcinomas were treated with recombinant alpha-2 interferon. Each patient had a biopsy-proved basal cell carcinoma of the nodular or superficial type that was injected intralesionally three times a week for 3 weeks (9 total injections) with 1.5 X 10(6) IU (0.15 ml) of alpha-2 interferon per injection (total dose, 13.5 X 10(6) IU). Excisional biopsy 2 months after completion of therapy revealed no evidence of basal cell carcinoma in any patient. Minimal side effects were observed. In these eight patients alpha-2 interferon was therefore an effective and safe modality of treatment. The encouraging results of this pilot study suggest that additional evaluation of interferon in the treatment of basal cell carcinoma is warranted.

Intralesional recombinant alpha-2 interferon for the treatment of patients with condyloma acuminatum or verruca plantaris.

We conducted a multicenter double-blind study comparing human recombinant intralesional alpha-2 interferon (IFN) and placebo in 237 patients with the clinical diagnosis of condyloma acuminatum or verruca plantaris. A single wart on each patient was injected with 0.1 mL containing 10(6) IU of IFN, 10(5) IU of IFN, or placebo three times weekly for three weeks, and the response to treatment was followed up for 12 weeks. Among 91 of the 114 patients with condyloma acuminatum who completed the study, complete clearing of the treated wart occurred in 16 (53%) of 30 patients receiving 10(6) IU of IFN compared with six (19%) of 32 receiving 10(5) IU of IFN and four (14%) of 29 receiving placebo. In the group of 100 patients with plantar warts, there was no apparent benefit associated with interferon administration. Seven patients (3%) had treatment discontinued due to adverse reactions. Intralesional alpha-2 IFN is of benefit in the treatment of a single condyloma; its role in the treatment of multiple lesions remains to be clarified. Its role in the treatment of verruca plantaris, where no response was seen, also remains to be clarified.

Marketing considerations in home health care.

Methods for conducting a comprehensive analysis of the potential for strategic entry or expansion in the home health-care (HHC) market are discussed. By conducting a comprehensive analysis of the HHC market, hospital pharmacists can evaluate the feasibility of developing and implementing a hospital-based HHC service. A comprehensive market analysis should include an initial assessment of potential product-line offerings, development of strengths-and-weaknesses and opportunities-and-threats profiles, evaluations of competing providers of HHC and regulatory issues, and formulation of a business plan. The potential impact of program structure, operations management, product pricing, advertising and promotion, and marketing controls should also be considered. The hospital pharmacist has a unique opportunity to further the organizational objectives of the hospital by participating in the provision of HHC; a comprehensive market analysis represents a useful method of assessing the benefits and costs associated with providing integrated HHC services.

Health care cost-containment in a changing health care world.

Home health care, particularly antibiotic home health care, must be studied against a background of change. Hospitals are changing their structure as one way of coping with health care costs. The Health Care Financing Administration is making its impact with the DRG program. As a result, hospitals are seeking various means of cost containment, and home health care is seen as one possible answer. Much of the potential benefit to be derived from home health care will depend on how thoroughly it is based on good modern technology, and how carefully it is planned to reduce hospital length of stay and to decrease the costs of hospital personnel and supplies. Another answer may be found in the administration of parenteral antibiotics by once-daily doses.

Cost containment of reconstituted parenteral antibiotics: personnel and supply costs associated with preparation, dispensing, and administration.

Time-and-motion studies were conducted to determine the time and cost associated with the dispensing, preparation, and administration of reconstituted parenteral antibiotics via the piggyback iv admixture (PBS) or volume control iv set administration (VCS) methods in six hospitals of various sizes. Supply costs were calculated for each system. National projections of potential cost savings resulting from decreased number of administrations of reconstituted parenteral antibiotics were made. The antibiotic class of parenteral cephalosporins was chosen as an example of where cost containment might be achieved. The estimated potential for total cost containment for the average hospital per hospital bed resulting from decreased number of administrations of first- and second-generation cephalosporins ranged from $76.64 (25% reduction in doses administered) to $229.92 (75% reduction) for the PBS method and, similarly, $47.02 to $141.08 for the VCS method. The projected potential national cost savings resulting from decreased number of administrations of first- and second-generation cephalosporins based on predicted antibiotic usage for 1983 ranged from $62.2 million (25% reduction in doses administered and adjusting for no conversion to intramuscular or intravenous push administrations) to $276.7 million (75% reduction). Clinicians and health-care managers should consider the cost-containment advantages provided by the substitution of newer antibiotics that permit reduced frequency of administration.

Cost containment associated with decreased parenteral antibiotic administration frequencies.

Multi-region time and motion studies were conducted in hospitals of various sizes to determine the cost of personnel and supplies associated with the preparation, dispensing, and administration of reconstituted parenteral antibiotics. The administration systems studied included the piggyback intravenous admixture (including several batch methodologies), the volume control intravenous set, and intramuscular techniques. Supply costs were calculated for each system. Projections of potential cost savings resulting from decreased administrations of parenteral cephalosporins were calculated for surgical prophylaxis, 10-day treatment course, and average per bed hospital use. The projected cost savings for the first 24 hours of surgical prophylaxis, or a 10-day treatment course changing from every eight- to six-hour dosing to a single daily dose ranged from $5.60 to $24.25 and $28 to $145, respectively. The average hospital's projected cost savings potential per hospital bed resulting from decreased administration of parenteral cephalosporins depended on the administration system or systems used and ranged from $35 (25 percent reduction in doses) to $364 (75 percent reduction in doses). An algorithm is presented for individual hospitals to use in calculating cost containment estimates. Clinicians and health care managers should seriously consider the cost containment advantages provided by the substitution of newer antibiotics which permit reduced administration frequency.

Evaluation of a 2-liter plastic container for parenteral nutrient solutions.

Cost effectiveness and clinical applicability of 2-liter flexible polyvinyl chloride containers for administration of total parenteral nutrient (TPN) solutions were studied. Times were measured for single and batch compounding of 50 2-liter and 50 1-liter TPN solutions and for nursing time associated with administration of 20 1-liter and 20 2-liter TPN solutions. Costs were calculated for personnel time and supplies for 100 1-liter and 50 2-liter TPN solutions using single and batch compounding. Rates of return, reuse, and waste were compared during a two-month period. Questionnaires were administered to nurses and physicians to measure acceptance of 2-liter containers. Time savings for 2-liter versus 1-liter containers were 7.33 and 3.06 minutes per 2-liter container for individual and batch processing, respectively. Nursing time saved with use of 2-liter containers was 2.79 minutes per 2-liter container. Total personnel and supply costs for 2-liter containers were $ 1.60 and $ 0.70 less per liter for individual and batch processing, respectively. For 2-liter TPN solutions prepared for 11 patients (129 patient days), waste was not significantly different than for the 1-liter control group. Questionnaire responses indicated overall acceptance of administration of 2-liter solutions as safe and efficient. For centrally administered TPN therapy in the inpatient setting, use of 2-liter flexible polyvinyl chloride containers is efficient and cost effective.

Common and uncommon cutaneous findings in patients with ataxia-telangiectasia.

This series describes some common and uncommon cutaneous findings in twelve patients with ataxia-telangiectasia (A-T). All patients had the characteristic telangiectasia as described previously. However, the telangiectases did not conform to a classic photodistribution . Our series did include one patient with a pathologic reaction to light-simulating hydroa aestivale or vacciniforme . In addition, there were three patients with acanthosis nigricans in two unrelated families. Vitiligo, impetigo, recurrent herpetic gingivostomatitis, hirsutism, lipoatrophy, gray hair, progeroid changes and hyper- and hypopigmented macules were noted in our patients. Many of our patients had one or more caf'e au lait like-lesions in a dermatomal distribution. In addition, several of the family members showed one or more café au lait-like lesions, suggesting the possibility that this finding may represent a phenotypic expression in the skin of carriers of this cancer-prone syndrome.

Shared pharmaceutical services in small hospitals.

A system of shared pharmaceutical services between two small, rural hospitals is described. A contractural agreement was established between a 140-bed hospital and a 40-bed hospital located 15 miles apart in a rural area of eastern Kentucky. The larger hospital provided comprehensive pharmaceutical services to the smaller hospital for a monthly fee. Procurement of i.v. fluids and supplies was a function of the larger hospital; other drugs and supplies were procured separately. The director of pharmacy at the larger institution also served as the director at the small institution. Staff pharmacists rotated between the two hospitals. Supportive personnel were assigned permanently to each hospital. The shared service arrangement reduced costs associated with the implementation of comprehensive pharmaceutical services and made it easier to recruit and retain skilled pharmacy personnel.