Elemental analysis of a single-wall carbon nanotube candidate reference material.

A material containing single-wall carbon nanotubes (SWCNTs) with other carbon species, catalyst residues, and trace element contaminants has been prepared by the National Institute of Standards and Technology for characterization and distribution as Standard Reference Material SRM 2483 Carbon Nanotube Soot. Neutron activation analysis (NAA) and inductively coupled plasma mass spectrometry (ICP-MS) were selected to characterize the elemental composition. Catalyst residues at percentage mass fraction level were determined with independent NAA procedures and a number of trace elements, including selected rare earth elements, were determined with NAA and ICP-MS procedures. The results of the investigated materials agreed well among the NAA and ICP-MS procedures and good agreement of measured values with certified values was found in selected SRMs included in the analyses. Based on this work mass fraction values for catalyst and trace elements were assigned to the candidate SRM.

Loss of Cdh1 and Trp53 in the uterus induces chronic inflammation with modification of tumor microenvironment.

Type II endometrial carcinomas (ECs) are estrogen independent, poorly differentiated tumors that behave in an aggressive manner. As TP53 mutation and CDH1 inactivation occur in 80% of human endometrial type II carcinomas, we hypothesized that mouse uteri lacking both Trp53 and Cdh1 would exhibit a phenotype indicative of neoplastic transformation. Mice with conditional ablation of Cdh1 and Trp53 (Cdh1(d/d)Trp53(d/d)) clearly demonstrate architectural features characteristic of type II ECs, including focal areas of papillary differentiation, protruding cytoplasm into the lumen (hobnailing) and severe nuclear atypia at 6 months of age. Further, Cdh1(d/d)Trp53(d/d) tumors in 12-month-old mice were highly aggressive, and metastasized to nearby and distant organs within the peritoneal cavity, such as abdominal lymph nodes, mesentery and peri-intestinal adipose tissues, demonstrating that tumorigenesis in this model proceeds through the universally recognized morphological intermediates associated with type II endometrial neoplasia. We also observed abundant cell proliferation and complex angiogenesis in the uteri of Cdh1(d/d)Trp53(d/d) mice. Our microarray analysis found that most of the genes differentially regulated in the uteri of Cdh1(d/d)Trp53(d/d) mice were involved in inflammatory responses. CD163 and Arg1, markers for tumor-associated macrophages, were also detected and increased in the uteri of Cdh1(d/d)Trp53(d/d) mice, suggesting that an inflammatory tumor microenvironment with immune cell recruitment is augmenting tumor development in Cdh1(d/d)Trp53(d/d) uteri. Further, inflammatory mediators secreted from CDH1-negative, TP53 mutant endometrial cancer cells induced normal macrophages to express inflammatory-related genes through activation of nuclear factor-κB signaling. These results indicate that absence of CDH1 and TP53 in endometrial cells initiates chronic inflammation, promotes tumor microenvironment development following the recruitment of macrophages and promotes aggressive ECs.

Role of the spleen in the transdiaphragmatic spread of Hodgkin's disease.

Results of detailed staging laparotomy for Hodgkin's disease with supradiaphragmatic presentation in 78 patients showed 28 with subdiaphragmatic involvement. All 28 patients with intra-abdominal disease had splenic involvement. On the basis of findings of this study and published series on staging laparotomy, it is proposed that the spleen is the first site of intra-abdominal disease in this group of patients, and that Hodgkin's disease spreads to the intra-abdominal lymph nodes, liver, and bone marrow from the spleen.

Autofluorescence of fungi: an aid to detection in tissue sections.

Many pathogenic fungi have been found to autofluoresce in routine hematoxylin and eosin sections when exposed to ultraviolet light. These fungi include Blastomyces, Cryptococcus, Candida, Aspergillus, Coccidioides, and occasionally, Histoplasma. No autofluorescence was observed with Mucor. Examinations of other inflammatory processes, including those producing a granulomatous response, have not revealed any false-positive results. The advantages of fluorescent microscopy for fungal screening include: (1) no special staining procedures required; (2) no time delay, as involved with special stains; (3) the ability to scan sections at a relatively low power; and (4) the ability to tentatively identify the fungus. Disadvantages may include: (1) lack of a fluorescent microscope, and (2) a possible aging process whereby autofluorescence is lost in older cases.

Endoglin expression as a measure of microvessel density in cervical cancer.

OBJECTIVE: To evaluate endoglin, a membrane protein and member of the transforming growth factor beta-1 receptor complex, as an endothelial marker of angiogenesis in cervical cancer tissues. METHODS: Tumor tissue was collected from 31 surgically treated stage IB nonbulky (under 5 cm) cervical cancer subjects, and samples were fixed in formalin and embedded in paraffin. Endoglin was stained on 5-microm slide sections by the DAKO Catalyzed Signal Amplification method (DAKO Corporation, Carpinteria, CA). Factor VIII was stained by standard immunohistochemistry. Positively stained microvessels were counted in "hot spots" at 200x magnification. Clinical data were correlated with vessel counts by Spearman correlation. Mean differences in counts were tested using paired t tests. RESULTS: This staining method for endoglin identified significantly more vessels than the factor VIII method (mean 92 +/- 45 versus 33 +/- 16, P <. 001). Endoglin and factor VIII counts correlated significantly with deep stromal invasion (Spearman rho 0.466 and 0.522, respectively, P <.05); however, only endoglin counts correlated significantly with lymph node metastases (rho =.495, P <.01). CONCLUSION: Endoglin is stimulated in tumor angiogenesis and might be relatively more specific than commonly used endothelial markers. The endoglin system was more sensitive for staining capillaries in neoplastic cervical tissue, better predicted lymph node metastases, and should be widely applicable for the study of other tumors.

Drug distribution: a philosophy.

Hospital pharmacy has made significant progress in the last two decades by any of a number of program evaluation methods. However equally apparent are our current deficiencies in the level of service provided in our drug distribution systems in Canadian hospitals. It is apparent that we will not be allowed to abrogate our responsibility any longer in that it is becoming recognized in medical, nursing and administrative circles that compounding and dispensing functions are clearly in the realm of a pharmacist's responsibility and these issues must be addressed if we can truly claim to be part of a world class health care system. Hospital pharmacists must take the initiative in accepting responsibility for chemotherapy preparations, I.V. additives and compounding as well as the adoption of a unit dose drug distribution system as a positive means to reduce medication errors. The report of the Hospital for Sick Children Review Committee makes it equally clear that society has expectations of an institutional pharmacy service that are considerably beyond that which we are accustomed to providing. The recommendations relating to pharmacy provide adequate support to facilitate the establishment of a contemporary drug distribution system in Canadian hospitals. Similarly the C.S.H.P. Standards of Pharmacy Practice and the Canadian Council on Hospital Accreditation Guidelines for Pharmacy Service offer additional "ammunition" for us individually and collectively to change the face of hospital pharmacy practice. The profession must take stock of its responsibilities before society insists that someone else take over where pharmacists have failed.

Direction through accreditation--CCHA (Canadian Council on Hospital Accreditation) recommendations to Ontario hospital pharmacies.

A questionnaire was circulated in December 1986 to 157 Ontario hospital pharmacy directors that asked about the recent recommendations made by CCHA surveyors. Sixty-four directors responded and assigned their received recommendations to four categories of pharmacy service. Similar recommendations were tabulated by category of service and by number of hospital beds (less than 200 and greater than 200 beds). The results show that drug distribution was the most emphasized area of service cited for improvement. Frequent recommendations concerned patient medication profiles, night supply services, hospital formulary, Pharmacy and Therapeutics Committee policy review, adverse drug reaction programs, quality assurance, and regular medication room checks. Responses indicated that 27 of the 62 eligible hospital pharmacies (44%) that received recommendations have acquired administrative support to implement changes, and 33 of 62 (53%) have had specific action as a result of an accreditation survey.

Clinical pharmacy services: Part II--the issues.

The development of clinical pharmacy programs over the past decade has been both dramatic and satisfying as well as divisive and frustrating. In our experience the broad spectrum of possible clinical activities is responsible for both situations as it concerns the individual pharmacist. At Sunnybrook, liaison pharmacists have accepted departmentally prioritized clinical activities as their primary focus while removed from the distribution system. Documentation for each individual staff member, satellite and departmental achievements for patient counselling, adverse reaction and drug information programs was undertaken to provide visible endpoints for both staff and administration. Hospital Pharmacy visibility to the lay public, a need expressed by several prominent practitioners, has been addressed by the production of a Pharmacy Services Brochure which helps to educate in-patients about our many programs. Lastly the attempt by several colleagues to evaluate the profession's clinical impact by means of a quality assurance program illustrates the difficult task ahead of us if we are to indeed demonstrate an improved patient care program through our efforts.

Survey of pharmacotherapy monitoring in Canadian acute care hospitals.

A survey questionnaire was sent to all hospitals in Canada that had 100 or more acute care beds. Objectives were to determine the current level and extent of pharmacist monitoring and prescriber acceptance of recommendations with respect to patient drug therapy. Three levels of patient drug therapy monitoring were identified, as were two extended forms of service. The response rate was 52.0 percent (130/250). A majority (92.3 percent) of respondents monitor drug therapy from the pharmacy, and only 6.2 percent provide monitoring service on patient wards. Among the respondents, 75.4 percent reviewed all (more than 90 percent) medication orders before the drug was dispensed for the patients. Of the respondents, 32.3 percent provided pharmacokinetic monitoring and 29.9 percent provided proactive pharmacist interventions via rounding with physicians. Higher levels of monitoring were associated with higher levels of pharmacy staffing. The acceptance rate of pharmacist recommendations by prescribers was more than 80 percent.

Drug utilization & therapeutic intervention programs: pharmacy services that pay for themselves.

This mailed survey was a follow-up to a 1989 study to assess the status of pharmacy-directed, drug-related, patient care programs in response to the Pharmaceutical Inquiry of Ontario (Lowy Inquiry). A specific focus on Therapeutic Interventions and Drug Utilization Review/Evaluation Programs was adopted because the earlier study indicated a significant "financial return" for pharmacist time spent on these initiatives. A response rate of 62.2% (89 out of 143 hospitals) was achieved compared with an 80% response rate in 1989. Therapeutic interventions were performed by 97.7% of hospitals which identified an average of 184 therapeutic interventions per month and an 84.3% acceptance rate by prescriber. Based on data from 53 hospitals, an average of 29 minutes was taken on each intervention and financial data from 10 hospitals showed cost savings/avoidance of $49.34 per intervention. Drug Utilization program data was available from 45% of hospitals and specific financial data was provided by 29.2% of institutions. Cost savings/avoidance data demonstrated a return of $29.99 for every dollar invested in pharmacist time performing these activities. Collectively, both programs were recognized for their value in optimizing pharmacotherapy, improving patient outcomes as well as demonstrating a financial return to the institution. Despite the recessionary times, these programs are easily justified since they more than pay their own way.

Clinical pharmacy activities: a quantitative assessment at Sunnybrook Medical Centre.

Levels of clinical pharmacy activity were assessed at Sunnybrook Medical Centre using levine et al's concept of Patient Care Units. Data from pharmacist-initiated log sheets (for two four-week periods) were collated and described under the headings of: "Average Clinical Time Per Day", "Number of Specific Clinical Encounters Per Month", "Average Percentage of Total Clinical Time Per Encounter", and "Average Time Per Specific Clinical Encounter". It was noted that only 21.7 to 26.0% of working time was spent on clinical interactions and that many of these activities did not involve patients. For example, clinical non-distributive interactions with professionals (other than physicians or nurses) and attendance at pharmacy educational functions, accounted for the largest portion of clinical time. Most of the patient encounters that did occur consisted of the indirect activity of chart review, instead of the more direct-discharge interviews, allergy verifications, and medication histories, it was apparent from the log sheet results that there was an individual prioritization of clinical activities by the Sunnybrook pharmacists. However, a departmental assumption that direct patient encounters had priority was not evident.

Serum drug level utilization: a literature analysis.

A literature analysis was performed to quantify and evaluate the amount of inappropriate utilization of serum drug level assays. Studies that determined appropriate use based on institution-specific criteria were extracted from the literature. Inappropriate use was categorized as to indication, sampling, or use of results. Canadian studies were isolated and compared to American studies. A total of 35 studies was identified as meeting the study criteria. The rates of inappropriate utilization of drug level assays were 34.7% for indication, 47.2% for sampling, and 40.2% for use of results. Twelve studies reported an overall average inappropriate use of 58.8%. Estimations of annual waste due to inappropriate blood level use ranged from $1,221 to $100,917 per hospital. Canadian studies reported rates of 37.2%, 52.5%, and 44.5% for the three categories, respectively, and an overall inappropriate rate of 53.3%. None of these values differed significantly from those of American studies (p greater than .1). It was concluded that there is a great deal of inappropriate drug level utilization that wastes much in terms of patient care, personnel time, and costs. A great potential exists for pharmacists to intervene and improve this area of drug utilization.

Fibrous dysplasia masquerading as chronic maxillary sinusitis.

Fibrous dysplasia is a rare disease of unknown cause that affects one or multiple bones. In its monostotic form, only one bone is involved. The maxilla is the most commonly affected facial bone. Facial deformity with or without pain is the most common presentation of fibrous dysplasia affecting the craniofacial bones. In certain cases the disorder can present clinically as chronic maxillary sinusitis. The clinical, radiologic, and histologic findings, as well as the differential diagnosis and treatment of this condition are reviewed.

Malignant acrospiroma.

A 76-year-old woman was referred after results of the biopsy of an ulcerated mass of the right long finger suggested poorly differentiated squamous cell carcinoma. Excision and skin grafting were done and a diagnosis of malignant acrospiroma was established. These tumors are aggressive and 5-year survival rate may be as low as 30%. A ray amputation was subsequently done and the specimen was without residual tumor. At 14 months follow-up, the patient remains free of disease.

An alternative method for the certification of the sulfur mass fraction in coal Standard Reference Materials.

The S mass fractions of coal SRMs 2682b, 2684b, and 2685b are certified by direct comparison with coal SRMs 2682a, 2684a, and 2685a, respectively, using high-temperature combustion analysis with infrared (IR) absorption detection. The S mass fractions of the "a" materials used for calibration were previously determined by means of isotope-dilution thermal-ionization mass spectrometry (ID-TIMS). Therefore, the comparisons performed with the combustion-IR absorption method establish direct traceability links to accurate and precise ID-TIMS measurements. The expanded uncertainties associated with the certified S mass fractions are of approximately the same magnitude as would be expected for the ID-TIMS methodology. An important aspect of these certifications is that each "b" material is essentially identical with the corresponding "a" material, because both were produced from the same bulk, homogenized coal. As a test of the efficacy of the new certification approach when calibrant and unknown are not identical, the S mass fraction of coal SRM 2683b has been determined by direct comparison to coal SRM 2683a. These two coals, which have both previously been analyzed with ID-TIMS, are different in terms of S content and other properties. Whereas the S mass fraction for SRM 2683b determined with the new methodology agrees statistically with the ID-TIMS value, there is reason for caution in such cases. In addition to the usefulness of the alternative approach for certification activities within NIST, this approach might also be an excellent way of establishing NIST traceability during the value assignment process for reference materials not issued by NIST. Further research is needed, however, to understand better the scope of applicability.