Comparative exposure ratios: A non-parametric,multifactor technique for case-control studies

The odds ratio in a two-by-two table is widely used in case-control studies to measure association between disease and a binary risk factor. In this article we propose a more general measure of association, the comparative exposure ratio (CER), which is the ratio of the number of case-control pairs where the case has greater exposure divided by the number where the control has greater exposure. In simple cases, the CER is an odds ratio or a weighted combination of odds ratios. In more general cases a CER continues to measure association even when an odds ratio computation is not feasible. Moreover, CERs improve on odds ratios in several ways: they do not require binary risk factors, or a choice of the scale of measurement of continuous risk factors; they make it possible to investigate multiple risk factors simultaneously, without multivariate parametric assumptions; they also can be used to detect patterns that might indicate possible causal pathways. We illustrate how various choices of the definition of ‘greater exposure’ make the CER a powerful and flexible tool. We give expressions for confidence intervals for CERs, and verify in a pilot simulation that they are valid. Finally, we illustrate with a case-control study of cervical dysplasia how exploratory inference using CERs can be carried out. (This research was partially supported by grants from the National Cancer Institute, CA 41108 and CA 25702).     

Social Implications of Hyperfunctional Facial Lines

The face is the focus of human interactions, and facial appearance profoundly affects self-esteem. Facial appearance is not only a compilation of the dimensions of the primary morphologic features but is also a direct result of the emotional expressions exhibited on the face. Facial expressions are central in the communication of emotions, as well as in signaling characteristics such as age. The repeated expression of emotions produces hyperfunctional facial lines, and the presence of these lines when the face is at repose may give an erroneous impression of emotions or personality characteristics. These lines are also perceived as a sign of aging. Treatment of hyperfunctional facial lines is beneficial for patients who believe that their faces are not communicating their emotions properly, who want to delay the outward appearance of aging, or who simply want to look their best.     

Acute reversible neurological deficit following intrathecal chemotherapy

Summary We report on two patients with non-Hodgkin's lymphoma (NHL) who developed reversible, short-lived neurological deficit following intrathecal (i.t.) chemotherapy. One patient received i.t. methotrexate for treatment of meningeal disease, and the other received i.t. methotrexate with cytosine arabinoside (ara-C) and hydrocortisone as central nervous system (CNS) prophylaxis. Although transient paresis following i.t. chemotherapy has previously been reported, it has been attributed to the previously contained in the diluents. Our two patients, however, received preservative-free solutions.     

Assessment of the potential allergenicity of ice structuring protein type III HPLC 12 using the FAO/WHO 2001 decision tree for novel foods.

The introduction of novel proteins into foods carries a risk of eliciting allergic reactions in individuals sensitive to the introduced protein. Therefore, decision trees for evaluation of the risk have been developed, the latest being proposed by WHO/FAO early in 2001. Proteins developed using modern biotechnology and derived from fish are being considered for use in food and other applications, and since allergy to fish is well established, a potential risk from such proteins to susceptible human beings exists. The overall aim of the study was to investigate the potential allergenicity of an Ice Structuring Protein (ISP) originating from an arctic fish (the ocean pout, Macrozoarces americanus) using the newly developed decision tree proposed by FAO/WHO. The methods used were those proposed by FAO/WHO including amino acid sequence analysis for sequence similarity to known allergens, methods for assessing degradability under standardised conditions, assays for detection of specific IgE against the protein (Maxisorb RAST) and histamine release from human basophils. In the present paper we describe the serum screening phase of the study and discuss the overall application of the decision tree to the assessment of the potential allergenicity of ISP Type III. In an accompanying paper [Food Chem. Toxicol. 40 (2002) 965], we detail the specific methodology used for the sequence analysis and assessment of resistance to pepsin-catalysed proteolysis of this protein. The ISP showed no sequence similarity to known allergens nor was it stable to proteolytic degradation using standardised methods. Using sera from 20 patients with a well-documented clinical history of fish allergy, positive in skin prick tests to ocean pout, eel pout and eel were used, positive IgE-binding in vitro to extracts of the same fish was confirmed. The sera also elicited histamine release in vitro in the presence of the same extracts. The ISP was negative in all cases in the same experiments. Using the proposed decision tree, we demonstrated the safety of the ISP to patients already sensitised to fish, as well as to individuals potentially susceptible to producing IgE responses to proteins. Furthermore, the practicability of the new decision tree was confirmed.     

Care of HIV-infected patients: nurses' concerns, opinions, and precautions

The purpose of this study was to describe nurses' concerns, opinions, and precautions related to nursing patients infected with the human immunodeficiency virus (HIV). Of special interest was a comparison of responses by nurses who reported exposure to the HIV through broken skin or mucous membranes with the responses of nurses who reported no such exposure. The sample included all staff nurses employed in either the ambulatory/home health care unit or in one of seven inpatient critical care units of a large urban medical center. Of the 323 respondents, 64 (20%) reported HIV exposure, 77 (24%) reported no exposure, and 180 (56%) reported not knowing if they had been exposed. A 15-item Likert-type scale was used. More HIV-exposed nurses than non-exposed nurses reported: (a) worrying about becoming HIV-infected; (b) considering a change of specialty or profession because of the acquired immunodeficiency syndrome (AIDS) risk; and (c) favoring selected HIV-related policies. Of the total sample, nearly all subjects agreed that staff nurses should be involved in developing HIV-related policies affecting nurses; and over one-half said that, if the agency gave them the option, they would refuse assignment to HIV-infected patients. Nearly 30% said that they had considered changing their profession because of the AIDS risk. Some implications are that nursing administrators should involve well-informed staff nurses in formulating HIV-related policies that affect nurses. The HIV-exposed nurses may need support in dealing with their concerns resulting from HIV-exposure, and they may need more information about HIV-infection control and seroconversion rates of HIV-exposed nurses.     

A simple and reliable pretreatment protocol facilitates fluorescent in situ hybridisation on tissue microarrays of paraffin wax embedded tumour samples.

AIMS: To describe a robust pretreatment protocol for preparing paraffin wax embedded tissues on tissue microarrays for fluorescence in situ hybridisation (FISH). The newly developed pretreatment protocol described here was compared with the commonly used sodium thiocyanate based protocol and two different heating methods used in standard antigen unmasking protocols for immunohistochemistry (pressure cooking and microwaving in citrate acid buffer). METHODS: Dewaxed tissue sections were incubated in 10mM citric acid buffer at 80 degrees C for 30 minutes to two hours, followed by a short pepsin digestion (1-5 mg/ml). Pretreated tissues were co-denatured with DNA probes at 80 degrees C for 10 minutes, followed by hybridisation at 37 degrees C for 48-72 hours. RESULTS: The three protocols using citrate acid buffer produced FISH signals with superior signal to noise ratios compared with sodium thiocyanate pretreatment. Most importantly, the best tissue attachment was achieved using the newly developed pretreatment protocol: on tissue microarrays less than 1% of cores were lost. To date, a total of 30 probes have been successfully hybridised on to breast tissue and multi-tissue microarrays. CONCLUSION: This pretreatment protocol is easy, reproducible, and facilitates FISH on tissue microarrays, with potential for widespread application in cancer research.     

Bisphosphonate (pamidronate/APD) prevents arthritis-induced loss of fracture toughness in the rabbit femoral diaphysis

Patients with rheumatoid and other inflammatory arthritis have an increased risk for fracture. This study was designed to determine the effect of experimental inflammatory arthritis on the material properties (fracture toughness and shear modulus) and structural properties (torque, angular defelection, and absorbed energy) of femoral diaphyseal bone tested in torsion to fracture, as well as the effect on these properties of APD (3-amino-1-hydroxypropylidene-1,1-bisphosphonate), a drug known to block osteoclast activity. Two dose levels were investigated. Experimental inflammatory arthritis was induced by intra-articular injection of carrageenan into the right tibiofemoral joint, given over 7 weeks, in three groups of animals. Simulataneously, daily subcutaneous injections of APD were given to three groups of rabbits. Five groups (12 animals each) were established: normal, arthritis, normal/high dose APD, arthritis/high dose APD, and arthritis/low dose APD. The diaphyses of each excised right femur were loaded to fracture in torsion at an angular deflection rate of 8°/sec. In the arthritis group, the fracture toughness was 39% lower than in the normal group, and the structural properties all were reduced significantly. By contrast, the shear modulus was unaffected by arthritis. In this study, the higher dose level (0.3 mg/kg of body weight) of APD prevented loss of fracture toughness and maintained the structural properties in experimental inflammatory arthritis; the low dose was not effective.     

Volatile General Anesthetics Produce Hyperpolarization of Aplysia Neurons by Activation of a Discrete Population of Baseline Potassium Channels

Background: The mechanism by which volatile anesthetics act on neuronal tissue to produce reversible depression is unknown. Previous studies have identified a potassium current in invertebrate neurons that is activated by volatile anesthetics. The molecular components generating this current are characterized here in greater detail.

Methods: The cellular and biophysical effects of halothane and isoflurane on neurons of Aplysia californica were studied. Isolated abdominal ganglia were perfused with anesthetic-containing solutions while membrane voltage changes were recorded. These effects were also studied at the single-channel level by patch clamping cultured neurons from the abdominal and pleural ganglia.

Results: Clinically relevant concentrations of halothane and isoflurane produced a slow hyperpolarization in abdominal ganglion neurons that was sufficient to block spontaneous spike firings. Single-channel studies revealed specific activation by volatile anesthetics of a previously described potassium channel. In pleural sensory neurons, halothane and isoflurane increased the open probability of the outwardly rectifying serotonin-sensitive channel (S channel). Halothane also inhibited a smaller noninactivating channel with a linear slope conductance of approximately 40 pS. S channels were activated by halothane with a median effective concentration of approximately 500 micro Meter (0.013 atm), which increased channel activity about four times. The mechanism of channel activation involved shortening the closed-time durations between bursts and apparent recruitment of previously silent channels.     

Fetal Oxygen Saturation Monitoring in Labour: An Analysis of 118 Cases

Summary: Fetal oxygen saturation (FSpO₂) was recorded during labour to determine the relationship between FSpO₂ and indicators of fetal well-being, including umbilical blood gases, xanthine (X), hypoxanthine (Hx) and Apgar scores. This is one of me largest reported series of fetal pulse oximetry, with 118 fetuses monitored for over 329 hours. Mean FSpO, for all cases was 46.9% (SD=9.1%). There was no correlation between FSpO, during the last 10 minutes of monitoring and arterial pH, Hx or X. A mean FSpO₂, ≤ 30% was associated with a 5 minute Apgar score of ≤ 7 in the majority of cases. One fetus had a mean FSpO₂, <30% during the final 10 minutes of monitoring and an umbilical arterial pH<7.20, while there were 10 fetuses with an umbilical arterial pH<7.20, and mean FSpO₂, ≥ 30%. As these numbers are small, a larger series is necessary to further characterize the small number of fetuses who are significantly hypoxic.