Fibromyalgia, chronic fatigue, and other iatrogenic diagnostic algorithms. Do some labels escalate illness in vulnerable patients?

Contemporary medicine has the sophistication to identify the clinical settings in which the hunt for a diagnosis can be harmful to a patient's health. Which patients are best served by a prolonged search for a cause? Why has the disease-illness paradigm backfired for so many patients? Dr Hadler challenges readers to look at the difficult questions linked with diagnostic labels that might teach patients to stay sick.     

Limitations of current diagnostic procedures for the diagnosis of Taenia solium cysticercosis in rural pigs

New evidence has been presented from our laboratory that the gliding bacterium, Myxococcus xanthus, does not home by chemotaxis toward a nutrient source. Our experiments, those of others, and the theory presented here combine to suggest a model, called the 'Pied Piper' model. It hypothesizes a gene that has a high mutation rate forward and back (say something in excess 10(-4) mutations per cell generation) which leads to switching between two motility states. Occasionally rare organisms become genetically, but reversibly, changed so that they move unidirectionally instead of mostly forward and back as do the bulk of the cells. When such a 'leader' cell arises, it continues to move in its original orientation, and causes a cohort of cells to move together away from the bulk of the cells. That is, in the less common mutational state it counteracts the usual tendency to just move forward and backward achieving little net movement. The assumption of a genetic element that mutates in a reversible way is suggested by numerous cases of reversible switches now known in a wide range of bacteria serving a variety of functions. A second aspect of the model is that mechanisms exist that cause cells to move in the same direction as their nearby neighbors. This process results in a regular spacing of bands of cells to form mounds in the absence of a leader. The action of C-factor, a factor-secreted by the cells which has been largely studied in the laboratory of Dale Kaiser, and extracellular fibrils, (rod-shaped protein and carbohydrate bodies) largely studied in the laboratory of Martin Dworkin, may be key elements in coordinating (or linking) the movements of neighboring cells. Based on the assumption of the absence of chemotaxis, computer simulations of pattern formation for gliding bacterial swarms and flares are consistent with observed behaviors and thus are additional evidence that chemotactic motility of the type exhibited by Escherichia coli, is not necessary for the group movements of M. xanthus. Some tests for this model are suggested.     

Cholesterolemia in colorectal cancer

BACKGROUND/AIMS: Colorectal cancer incidence is higher in developed countries. High fat intake is one of the risk factors. However, many studies observed lower cholesterol serum levels on diagnosis of colorectal cancer. The aim of this assay was to study the serum cholesterol levels in patients with colorectal cancer and compare these values with individuals of the same age and sex. METHODOLOGY: Cholesterol serum levels of 85 patients with colorectal cancer were determined. Each of the patients with colorectal cancer were matched with an individual without cancer of the same age and sex. Total cholesterol concentrations were determined using an enzymatic colorimetric method. RESULTS: The mean serum of cholesterol was 183.4 for the colorectal group and 209.7 for the control group. This difference was statistically significant. This difference was more evident in patients with colon cancer and older than 60 years of age. There was no difference between the different Dukes' stage. CONCLUSIONS: Our study suggest an association between low blood cholesterol and colorectal cancer. We believe that the lower level of cholesterol observed in these patients is a consequence between the difference of colorectal carcinogenesis.     

A pilot study of the marginal adaptation and surface morphology of glass-cermet cements

This study investigated changes in the marginal adaptation and surface morphology of Ketac-Silver and Chelon-Silver glass-current cements over time. Dispersalloy amalgam was used as a control. Contralateral pairs of carious primary molars were restored with the test materials and amalgam. Clinical evaluations were scheduled at 12, 18, and 24 months after placement. Gold-plated replicas of the restorations were observed with scanning electron microscopy. Fractures and cracks in the surface of the Dispersalloy and Chelon-Silver increased the surface roughness; however, the damage was superficial and self-limiting in the Dispersalloy restorations, while in Chelon-Silver the fractures caused the material to break down in layers. A substantial quantity of pores, usually smaller than 50 microns in diameter, were observed throughout the surface of the Chelon-Silver restorations. The pores in the surface of Ketac-Silver were fewer and smaller. The incidence of cavomarginal breakdown increased with time. Chelon-Silver restorations had a higher rate of cavomarginal breakdown than did Ketac-Silver and Dispersalloy restorations up to 18 months. However, there was no statistically significant difference in the marginal adaptation of the three groups at 24 months.     

Patients' experiences of patient-controlled analgesia

We examined patients' experiences of patient-controlled analgesia by the use of semistructured interviews in 26 patients shortly after discontinuation of the device. The options expressed by the patients were examined qualitatively to identify recurring themes in their experience of patient-controlled analgesia. The areas of interest were analgesia, factors influencing whether the patient pressed the button or not, whether they felt in control and side effects. Negative as well as the expected positive evaluations were found. The negative evaluations reflected problems with nausea and vomiting and inadequate analgesia. No clear strategy for pressing, or not pressing, the button emerged and the principle of control by the patient over their pain relief was not considered important.     

Conventional and hypobaric activation of an ultrasound contrast agent

Hypobaric activation is a new injection technique for use with the contrast agent EchoGen and, in this study, the agent's ability to produce parenchymal enhancement in vivo, with and without prior hypobaric activation, was investigated. Injections, ranging in dose from 0.05 to 0.5 mL/kg, were administrated through a peripheral vein to eight woodchucks with multiple hepatomas. At the 0.10 mL/kg dose level, seven of eight injections following hypobaric activation (88%) resulted in definite parenchymal enhancement. Conversely, dosages of 0.10 mL/kg without prior hypobaric activation produced no grey-scale changes. Only at the 0.4 and 0.5 mL/kg dosage level did the conventional administration technique obtain similar results (4 of 5 injections increased the echogenicity for a 0.4 mL/kg dose). These differences were statistically significant (p = 0.031). In vitro experiments were conducted to establish the physical mechanisms behind hypobaric activation. Relative measurements of contrast microbubble sizes were performed with a phase Doppler particle analyzer after hypobaric and after conventional (bolus) activation. Hypobaric activation produced approximately 20 times more microbubbles per unit volume than the conventional method. In conclusion, this investigation has demonstrated the benefits of prior hypobaric activation when performing in vivo contrast studies with EchoGen and determined the physical mechanisms behind this new injection technique. Hypobaric activation of EchoGen increases contrast enhancement and reduces dose size.     

Relation of self-image to body size and weight loss attempts in black women: the CARDIA study. Coronary Artery Risk Development in Young Adults

It has been suggested that the prevalence of obesity in black women is high partly because self-image in black women is not strongly dependent on body size. To determine associations between self-image, body size, and dieting behavior among black women, the authors assessed an Appearance Evaluation Subscale (AES) score (range, 1-5), a Body Image Satisfaction (BIS) score (range, 2-11), and reported dieting behavior in a population-based sample of 1,143 black women aged 24-42 years from the fourth follow-up examination (1992-1993) of the Coronary Artery Risk Development in Young Adults (CARDIA) Study. Lower AES and BIS scores indicate poorer self-image and lower body size satisfaction, respectively. After adjustment for age, education, smoking, and physical activity, women in the lowest, middle, and highest tertiles of body mass index (weight (kg)/height (m)2) had mean AES scores of 3.7, 3.3, and 2.9, respectively (p < 0.001), and mean BIS scores of 7.8, 6.7, and 5.9, respectively (p < 0.001). After additional control for body mass index as a continuous variable, both AES and BIS scores were inversely related to ever dieting, current dieting, and previous weight loss of 10 pounds (4.5 kg) or more in all tertiles of body mass index. These results suggest that among black women, a higher body mass index is associated with poorer self-image and lower body size satisfaction and that these perceptions may be an avenue to promoting weight control.     

1.85-A resolution crystal structure of human ornithine transcarbamoylase complexed with N-phosphonacetyl-L-ornithine. Catalytic mechanism and correlation with inherited deficiency

The crystal structure of human ornithine transcarbamoylase complexed with the bisubstrate analog N-phosphonacetyl-L-ornithine has been solved at 1.85-A resolution by molecular replacement. Deleterious mutations produce clinical hyperammonia that, if untreated, results in neurological symptoms or death (ornithine transcarbamylase deficiency). The holoenzyme is trimeric, and as in other transcarbamoylases, each subunit contains an N-terminal domain that binds carbamoyl phosphate and a C-terminal domain that binds L-ornithine. The active site is located in the cleft between domains and contains additional residues from an adjacent subunit. Binding of N-phosphonacetyl-L-ornithine promotes domain closure. The resolution of the structure enables the role of active site residues in the catalytic mechanism to be critically examined. The side chain of Cys-303 is positioned so as to be able to interact with the delta-amino group of L-ornithine which attacks the carbonyl carbon of carbamoyl phosphate in the enzyme-catalyzed reaction. This sulfhydryl group forms a charge relay system with Asp-263 and the alpha-amino group of L-ornithine, instead of with His-302 and Glu-310, as previously proposed. In common with other ureotelic ornithine transcarbamoylases, the human enzyme lacks a loop of approximately 20 residues between helix H10 and beta-strand B10 which is present in prokaryotic ornithine transcarbamoylases but has a C-terminal extension of 10 residues that interacts with the body of the protein but is exposed. The sequence of this C-terminal extension is homologous to an interhelical loop found in several membrane proteins, including mitochondrial transport proteins, suggesting a possible mode of interaction with the inner mitochondrial membrane.     

Sulfasalazine in the treatment of juvenile chronic arthritis: a randomized, double-blind, placebo-controlled, multicenter study. Dutch Juvenile Chronic Arthritis Study Group

AIMS: To determine whether left ventricular volumes and ejection fractions calculated from single plane two-dimensional echocardiograms using the algorithm (0.85A2L) correlate with those calculated using the biplane Simpson's method, and whether small changes in volumes and ejection fraction occurring post-infarction could be detected from single-plane as well as from biplane two-dimensional echocardiograms. METHODS AND RESULTS: Serial two-dimensional echocardiograms were obtained in 371 patients from the DEFIANT II trial a mean of 2 days, 1 week and 6 months post-infarction. Single plane volumes from the apical four chamber and apical long axis correlated closely with biplane Simpson's left ventricular volumes. Both single-plane left ventricular volumes significantly over-estimated biplane Simpson's volumes. Biplane Simpson's ejection fractions were consistently slightly under-estimated from the single-plane images. Differences between biplane Simpson's and single-plane volumes increased independently with increasing left ventricular size and distortion. The small changes in left ventricular volumes and ejection fraction over time were as reliably detected from single plane as from biplane images. CONCLUSION: Single-plane left ventricular volumes over-estimate biplane Simpson's volumes and under-estimate ejection fraction, and these discrepancies are amplified in dilated hearts with abnormal shape.