Inter- and intraobserver variability in the histopathological diagnosis of medullary carcinoma of the breast,and its prognostic implications

Summary One hundred thirty-one breast carcinomas with medullary features, registered in the Danish Breast Cancer Cooperative Group from 1977–1982, have been histopathologically reviewed by two senior pathologists and classified as typical medullary carcinoma (TMC), atypical medullary carcinoma (AMC), and non-medullary carcinoma (NMC). Diagnostic criteria were based on those put forward by Ridolfiet al. and Fisheret al. The procedure was repeated with an interval of about one year by both pathologists. The diagnostic interobserver agreement was 72% with a Kappa of 0.55. The intraobserver agreement was 77% and 63% with Kappa values of 0.64 and 0.44, respectively. To see whether the observed inter- and intraobserver variability had any prognostic implications, diagnostic subgroups for both pathologists were analyzed with Kaplan Meier plots for recurrence-free survival (RFS) and with log rank tests. In the first evaluation pathologist 1 segregated a group of TMC with a significantly better RFS than for the NMC group, and pathologist 2 segregated a group of TMC with a corresponding strong trend. These findings could not, however, be reproduced in the second evaluation. The study indicates that the criteria of TMC and AMC as proposed by Ridolfiet al. need to be sharpened and simplified in order to reduce inter-and intraobserver variability. Larger studies with a control group of infiltrating ductal carcinomas are mandatory to elucidate the clinical importance of the diagnoses of Typical and Atypical Medullary Carcinoma of the breast.     

Effects of alkyl chain length on the inhibition of NNK-induced lung neoplasia in A/J mice by arylalkyl isothiocyanates

Six homologous arylalkyl isothiocyanates were evaluated fortheir abilities to inhibit pulmonary adenomas induced by thetobacco-specific nitrosamine 4-(methylnitrosamino)-l-(3-pyridyl)-1-butanone(NNK) in A/J mice. Four consecutive daily doses (5 µmol/mouse)of phenyl isothiocyanate (PITC), benzyl isothiocyanate (BITC),phenethyl isothiocyanate (PETTC), 3-phenylpropyl isothiocyanate(PPITC), 4-phenylbutyl isothiocyanate (PBITC), 4-oxo-4-(3-pyridyl)-butylisothiocyanate (OPBITC) and corn ofl were administered to miceby gavage. Two hours following the final dosing, mice were administeredsaline or 10 µmol of NNK in saline i.p. Pulmonary adenomaswere counted at 16 weeks after NNK administration. The miceadministered only corn oil prior to NNK developed an averagemultiplicity of 9.2 tumors/ mouse. Pretreatment with PITC, BITCand OPBITC had no significant effects on NNK-induced lung neoplasia.However, PEITC pretreatment resulted in a 64% reduction of lungtumor multiplicity, but did not affect the percentage of micethat developed tumors. Both PPITC and PBITC decreased tumormultiplicity by 96% and the percentage of tumor-bearing animalsby >60%. These results, in conjunction with our previouswork, demonstrate a general trend of increasing inhibition ofNNK-induced lung neoplasia by arylalkyl isothiocyanates withincreasing alkyl chain length. This study also demonstratesthe remarkable inhibitory activities of PPITC and PBITC, twoisothiocyanates that had not previously been tested as chemopreventiveagents.     

Monitoring of Neuromuscular Blockade at the P6 Acupuncture Point Reduces the Incidence of Postoperative Nausea and Vomiting

Background: Electrical stimulation of the P6 acupuncture point reduces the incidence of postoperative nausea and vomiting (PONV). Neuromuscular blockade during general anesthesia can be monitored with electrical peripheral nerve stimulation at the wrist. The authors tested the effect of neuromuscular monitoring over the P6 acupuncture point on the reduction of PONV.

Methods: In this prospective, double-blinded, randomized control trial, the authors investigated, with institutional review board approval and informed consent, 220 women undergoing elective laparoscopic surgery anesthetized with fentanyl, sevoflurane, and rocuronium. During anesthesia, neuromuscular blockade was monitored by a conventional nerve stimulator at a frequency of 1 Hz over the ulnar nerve (n = 110, control group) or over the median nerve (n = 110, P6 group) stimulating at the P6 acupuncture point at the same time. The authors evaluated the incidence of nausea and vomiting during the first 24 h.

Results: No differences in demographic and morphometric data were found between both groups. The 24-h incidence of PONV was 45% in the P6 acupuncture group versus 61% in the control group (P = 0.022). Nausea decreased from 56% in the control group to 40% in the P6 group (P = 0.022), but emesis decreased only from 28% to 23% (P = 0.439). Nausea decreased substantially during the first 6 h of the observation period (P = 0.009). Fewer subjects in the acupuncture group required ondansetron as rescue therapy (27% vs. 39%; P = 0.086).     

American Association of Critical-Care Nurses' national survey of facilities and units providing critical care.

BACKGROUND: Little information is available nationally about critical care units and nurses. What is known about nurses in hospitals is generally not broken down among all the specialties. OBJECTIVES: To describe issues of workforce, compensation, and care specific to critical care units and nurses who work in them. METHODS: The American Association of Critical-Care Nurses conducted a survey of randomly selected facilities with critical care units in the United States. Facilities were solicited via e-mail to respond to a survey on the World Wide Web and provide information on operations, evaluations, nursing staff reimbursement and incentives, staffing, and quality indicators. Responding facilities also provided contact information for units in the facilities. Those units were surveyed about operations, acuity systems, staffing, policies on visitation and end-of-life care, administrative structure, documentation, certification, professional advancement, vacancy/floating, staff satisfaction, orientation, association membership, wages, advanced practice nursing, and quality indicators. RESULTS: The initial response rate (120 of 658 eligible facilities) was 18.2%, and 300 of 576 solicited units nominated by the facilities responded, yielding a 52.1% response rate for the second phase. CONCLUSIONS: These survey data define the scope and intensity of services offered and provide more specific figures about staffing issues and unit practices than has been accessible before. Healthcare providers may use this information for benchmarking purposes, especially for instances in which the tables provide data for each particular type of critical care unit.     

Hyponatremia and the syndrome of inappropriate secretion of antidiuretic hormone associated with the use of selective serotonin reuptake inhibitors: a review of spontaneous reports.

OBJECTIVE: To review reported cases of hyponatremia and the syndrome of inappropriate secretion of antidiuretic hormone (SIADH) associated with the use of selective serotonin reuptake inhibitors (SSRIs). DATA SOURCES: A search of MEDLINE for reports of hyponatremia and SIADH associated with the use of fluoxetine, fluvoxamine, paroxetine or sertraline published between January 1980 and May 1995. Unpublished reports of cases were requested from the pharmaceutical industry, the Ontario Medical Association, the Health Protection Branch of Health Canada, the US Food and Drug Administration and the World Health Organization. DATA SELECTION AND EXTRACTION: Spontaneous reports from postmarketing surveillance. DATA SYNTHESIS: A total of 736 cases of hyponatremia [corrected] and SIADH associated with SSRI use were reported. Fluoxetine was involved in 554 (75.3%) of the cases, paroxetine in 91 (12.4%), sertraline in 86 (11.7%) and fluvoxamine in 11 (1.5%). Reports of 30 cases were published. The remaining 706 cases were reported to monitoring bodies and the pharmaceutical industry. According to information in the published reports, the median time to onset of hyponatremia was 13 days (range 3 to 120 days). Most (83%) of the published cases involved patients 65 years of age or more, as compared with 74% of the unpublished cases. CONCLUSION: Elderly people may be at increased risk for hyponatremia associated with SSRI use. Physicians caring for elderly patients should be aware of this potentially serious but reversible adverse effect. Further research is required to determine the incidence of this adverse effect, the relative risk of hyponatremia and SIADH in different age groups and the risk associated with different SSRI drugs.     

Physicochemical aspects of drug release. XV. Investigation of diffusional transport in dissolution of suspended, sparingly soluble drugs

The dissolution rates of sparingly soluble, fine particulate, suspended drugs have been studied using a Coulter Counter Model TAII. For two sieve fractions of oxazepam the dissolution rates were monitored in media with varying viscosities brought about by the addition of glycerol, while for griseofulvin the change in the medium's viscosity was induced by changing the temperature. By calculating the dissolution rate, and compensating for differences in particle surface area and media solubility, it was shown that the dissolution rate was diffusion controlled. After additional normalization for the diffusion coefficient, it was suggested that the so-called apparent diffusional distance decreased substantially with particle size. The effect of particle size was more limited above approx. 15 μm.     

Perceptions of admission committee members: some aspects on individual admission to dental education at Karolinska Institutet

The aim of the study was to generate an overall impression of the admission committee's (AC) perspective on individualised admission procedures, derived from some perceived experience of the individual committee members using semi-structured interviews. Qualitative research was used and data were collected by use of interviews. The results show that the committee members are highly committed to the task and try to identify desirable, non-cognitive attributes in the applicants, such as motivation, empathy, drive, and tenacity: 'emotional intelligence'. The committee members were of the opinion that it was possible to identify these attributes in an applicant. The AC further believes that the admissions procedure influences academic achievements because students regard themselves as specially selected and therefore aspire to higher achievements.