Cluster analysis and disease mapping--why, when, and how? A step by step guide

Growing public awareness of environmental hazards has led to an increased demand for public health authorities to investigate geographical clustering of diseases. Although such cluster analysis is nearly always ineffective in identifying causes of disease, it often has to be used to address public concern about environmental hazards. Interpreting the resulting data is not straightforward, however, and this paper presents a guide for the non-specialist. The pitfalls include the fact that cluster analyses are usually done post hoc, and not as a result of a prior hypothesis. This is particularly true for investigations prompted by reported clusters, which have the inherent danger of overestimating the disease rate through "boundary shrinkage" of the population from which the cases are assumed to have arisen. In disease surveillance the problem of making multiple comparisons can be overcome by testing for clustering and autocorrelation. When rates of disease are illustrated in disease maps undue focus on areas where random fluctuation is greatest can be minimised by smoothing techniques. Despite the fact that cluster analyses rarely prove fruitful in identifying causation, they may-like single case reports-have the potential to generate new knowledge.     

Sleep problems of junior high school students in Taipei

The objective of this work was to study the relationship between daily sleep time and characteristics of students, e.g. grade level, gender, and academic program. A sleep habit questionnaire was designed to survey students at two junior high schools, one from northern Taipei and the other from southern Taipei. The impact of shortened duration of sleep on daily function was also evaluated. A total of 965 students and their parents were selected randomly in December 1993 for the questionnaire study. The response rate was 96.4% (930) for students and 88.6% (855) for parents. The self-reported daily sleep time of students declined, and daytime sleepiness and moodiness increased in the higher grades. The girls slept fewer hours than the boys and did not show an increase in daytime sleepiness. Those students not taking the senior high school joint entrance examination slept more hours at night and maintained more alertness in the daytime than those who were taking the examination. The more academic pressures that adolescents faced, the fewer hours they slept. Students not participating in the joint entrance examination seemed to show a healthier sleep pattern. Little sleep at night made the students feel sleepy in the daytime and tired, drowsy, moody and difficult at arising in the morning. The reason why girls slept less than boys needs further investigation.     

Monoclonal antibodies recognizing epitopes on the extracellular face and intracellular N-terminus of the human erythrocyte anion transporter (band 3) and their application to the analysis of South East Asian ovalocytes

This report describes the production and characterization of 13 rodent monoclonal antibodies to the human erythrocyte anion transport protein AE1 (syn. band 3). Eleven antibodies (4 murine and 7 rat) recognize epitopes dependent on the integrity of the third extracellular loop of the protein. Two antibodies (1 murine and 1 rat) recognize epitopes on the N-terminal cytoplasmic domain. Quantitative binding studies using radioiodinated IgG and Fab fragments of antibodies to extracellular epitopes on AE1 ranged from 77,000 to 313,000 (IgG) and from 241,000 to 772,000 (Fab) molecules bound at saturation. The results indicate that the epitopes recognized by different antibodies vary in their accessibility and suggest that there is heterogeneity in the organization of individual AE1 molecules in the red blood cell membrane. Quantitative binding studies on South East Asian ovalocytes using several antibodies to AE1 and an anti-Wrb show a marked reduction in the number of antibody molecules bound at saturation. These results are consistent with the existence of highly cooperative interactions between transmembrane domains of AE1 in normal erythrocytes and the disruption of these interactions in the variant AE1 found in South East Asian ovalocytes.     

Voltage-dependent calcium channel promoter restores baroreflex sensitivity in conscious dogs with heart failure

BACKGROUND: The aim of this study was to determine the mechanism by which the calcium channel promoter BAY y 5959 affects the control of heart rate and baroreflex sensitivity in conscious dogs with pacing-induced heart failure (HF). METHODS AND RESULTS: We compared responses to BAY y 5959, which increases inotropy and decreases chronotropy, with those to norepinephrine (NE), which coincidentally exerts the same directional effects on inotropy and chronotropy, albeit through different mechanisms, in the presence and absence of ganglionic blockade both in control and in HF. Both BAY y 5959 and NE elicit direct effects on the heart and indirect effects through activation of reflexes, primarily the sinoaortic baroreceptor reflex. BAY y 5959 still reduced heart rate in dogs with arterial baroreceptor denervation, but not after ganglionic blockade. HF induced classic catecholamine desensitization to the inotropic effects of NE and blunted reflex bradycardia. In contrast, inotropic responses to BAY y 5959 were preserved in HF. Surprisingly, the autonomically mediated bradycardia induced by BAY y 5959 was also preserved in HF. Baroreflex sensitivity was assessed in control and in HF by pulse interval-systolic arterial blood pressure (PI/SAP) slopes constructed in response to pharmacological alterations in arterial pressure. HF depressed the PI/SAP slope from 11.5+/-1.3 to 4.8+/-0.9 ms/mm Hg, but during BAY y 5959 infusion in HF, the PI/SAP slope was restored to 24.1+/-5.2 ms/mm Hg. To assess central versus peripheral actions of BAY y 5959, the agent was infused with intra-carotid artery perfusion at a low dose, which acted centrally but did not have an effect peripherally. Under these conditions, it still decreased heart rate and restored baroreflex sensitivity (PI/SAP slope, 12.7+/-2.8 ms/mm Hg). CONCLUSIONS: Thus, the calcium promoter restores arterial baroreflex sensitivity in HF. Based on intra-carotid artery experiments, this occurs through a central nervous system and vagal mechanism.     

Videoendoscopic diagnosis of esophageal motility disorders

PURPOSE: Looking for a valid, reliable, and feasible method to collect data on the performances of practicing family physicians, the authors compare the measurement characteristics of a multiple-station examination (MSE) using standardized patients with those of a video assessment of regular consultations in daily practice (practice video assessment, PVA). METHOD: In a cross-sectional study, consultations of 90 family physicians were videotaped both in an MSE and in their daily practices. Peer-observers used a validated instrument (MAAS-Global) to assess the physicians' communication with patients and their medical performances. The physicians were randomly divided into two groups, comparable for demographic characteristics, and half underwent the assessments in reverse order to test for time-order effects. Content validity, criterion validity, reliability, and feasibility of the two methods were compared. RESULTS: Content validity of the PVA was superior to that of the MSE, since the domain of general family practice care was better covered. Observed participants judged the videotaped practice consultations to be "natural," whereas hardly any family physician, after reviewing the videotaped consultations of the MSE, recognized his or her usual working style. Specific criteria made it possible to standardize real practice. Concerning criterion validity, only the medical-performance components of the two methods correlated. No correlation was found for the communication components. Real-practice performance proved to be less influenced by observation than was performance during the MSE. The reliabilities of the two methods, expected to be better in the controlled MSE, were comparable. The administration of the PVA was more flexible, less costly, and better accepted by the family physicians than was that of the MSE. CONCLUSION: Assessment for quality improvement of family physicians' practices by video observation in daily practice is superior to video assessment in a simulated setting using standardized patients.     

Transduction of full-length TAT fusion proteins into mammalian cells: TAT-p27Kip1 induces cell migration

Human procathepsin L has been expressed in E. coli in the form of inclusion bodies. The recombinant protein was isolated, refolded and processed at pH 5.5 by the addition of dextran sulfate which increased the overall yield of cathepsin L almost 10-fold. After the auto-activation of the 38 kDa procathepsin L at least three processing sites were determined by N-terminal amino acid sequencing. After replacing the Ala205 residue by glutamic acid, cathepsin B-like specificity was introduced into cathepsin L. This mutation resulted in a 15-fold increased activity toward the substrate Z-Arg-Arg-AMC and in a 29-fold decreased activity toward Z-Phe-Arg-AMC. Residue 205 is thereby confirmed experimentally to be critical for the specificity of cathepsins B and L.     

Fourier transform Raman spectroscopy of polyacrylamide gels (PAGs) for radiation dosimetry

Polyacrylamide gels (PAGs) are used for magnetic resonance imaging radiation dosimetry. Fourier transform (FT) Raman spectroscopy studies were undertaken to investigate cross-linking changes during the copolymerization of polyacrylamide gels in the spectral range of 200-3500 cm(-1). Vibrational bands of 1285 cm(-1) and 1256 cm(-1) were assigned to acrylamide and bis-acrylamide single CH2 deltaCH2 binding modes. Bands were found to decrease in amplitude with increasing absorbed radiation dose as a result of copolymerization. Principal component regression was performed on FT-Raman spectra of PAG samples irradiated to 50 Gy. Two components were found to be sufficient to account for 98.7% of the variance in the data. Cross validation was used to establish the absorbed radiation dose of an unknown PAG sample from the FT-Raman spectra. The calculated correlation coefficient between measured and predictive samples was 0.997 with a standard error of estimate of 0.976 and a standard error of prediction of 1.140. Results demonstrate the potential of FT-Raman spectroscopy for ionizing radiation dosimetry using polyacrylamide gels.     

Causes of upper extremity compartment syndrome

Multiple causes, including various types of trauma, prolonged compression, muscle avulsions, burn, snake bites, high-pressure injection injuries, exercise, infection, bleeding, and intravenous drug infiltration, have been reported to lead to the development of a compartment syndrome in the upper extremity. Awareness of the different causes and risks of compartment syndrome should facilitate early diagnosis and prompt treatment to help avoid the development of serious sequelae such as Volkmann's ischemic contracture. A review of the various reports of upper extremity compartment syndromes and classification systems is presented to assist in the understanding of this condition's development.