Chronic fatigue syndrome: identifying zebras amongst the horses

There are currently no investigative tools or physical signs that can confirm or refute the presence of chronic fatigue syndrome (CFS). As a result, clinicians must decide how long to keep looking for alternative explanations for fatigue before settling on a diagnosis of CFS. Too little investigation risks serious or easily treatable causes of fatigue being overlooked, whilst too many increases the risk of iatrogenic harm and reduces the opportunity for early focused treatment. A paper by Jones et al published this month in BMC Medicine may help clinicians in deciding how to undertake such investigations. Their results suggest that if clinicians look for common psychiatric and medical conditions in those complaining of prolonged fatigue, the rate of detection will be higher than previously estimated. The most common co-morbid condition identified was depression, suggesting a simple mental state examination remains the most productive single investigation in any new person presenting with unexplained fatigue. Currently, most diagnostic criteria advice CFS should not be diagnosed when an active medical or psychiatric condition which may explain the fatigue is identified. We discuss a number of recent prospective studies that have provided valuable insights into the aetiology of chronic fatigue and describe a model for understanding chronic fatigue which may be equally relevant regardless of whether or not an apparent medical cause for fatigue can be identified

Multiplex Zymography Captures Stage-specific Activity Profiles of Cathepsins K, L, and S in Human Breast, Lung, and Cervical Cancer

<p>Abstract</p> <p>Background</p> <p>Cathepsins K, L, and S are cysteine proteases upregulated in cancer and proteolyze extracellular matrix to facilitate metastasis, but difficulty distinguishing specific cathepsin activity in complex tissue extracts confounds scientific studies and employing them for use in clinical diagnoses. Here, we have developed multiplex cathepsin zymography to profile cathepsins K, L, and S activity in 10 μg human breast, lung, and cervical tumors by exploiting unique electrophoretic mobility and renaturation properties.</p> <p>Methods</p> <p>Frozen breast, lung, and cervix cancer tissue lysates and normal organ tissue lysates from the same human patients were obtained (28 breast tissues, 23 lung tissues, and 23 cervix tissues), minced and homogenized prior to loading for cathepsin gelatin zymography to determine enzymatic activity.</p> <p>Results</p> <p>Cleared bands of cathepsin activity were identified and validated in tumor extracts and detected organ- and stage-specific differences in activity. Cathepsin K was unique compared to cathepsins L and S. It was significantly higher for all cancers even at the earliest stage tested (stage I for lung and cervix (n = 6, p < .05), and stage II for breast; n = 6, p < .0001). Interestingly, cervical and breast tumor cathepsin activity was highest at the earliest stage we tested, stages I and II, respectively, and then were significantly lower at the latest stages tested (III and IV, respectively) (n = 6, p < 0.01 and p < 0.05), but lung cathepsin activity increased from one stage to the next (n = 6, p < .05). Using cathepsin K as a diagnostic biomarker for breast cancer detected with multiplex zymography, yielded 100% sensitivity and specificity for 20 breast tissue samples tested (10 normal; 10 tumor) in part due to the consistent absence of cathepsin K in normal breast tissue across all patients.</p> <p>Conclusions</p> <p>To summarize, this sensitive assay provides quantitative outputs of cathepsins K, L, and S activities from mere micrograms of tissue and has potential use as a supplement to histological methods of clinical diagnoses of biopsied human tissue.</p

Geochemistry of lower proterozoic greywackes from the Birim diamondiferous field, Ghana

The Birim Diamondiferous field from which most of the alluvial diamonds are recovered is underlain by Lower Proterozoic Birimian metasedimentary and associated mafic rocks. Bulk rock geochemistry was carried out on the sandstones from the metasedimentary rocks to constrain the tectonic setting during the early Proterozoic. Bulk rock geochemical studies on greywackes show that they are characterized by moderately low but variable SiO2 contents, generally high Al2O3 and ferromagnesian element (e.g., Fe, Mg, Cr, V, Co, Sc) contents, and K2O/Na20 commonly less than 1. The geochemical data indicate that the greywackes were deposited in an active continental margin environment. The detritus were mainly derived from the upper continental crust but with an admixture of mafic component. Recent studies have shown that some of the mafics/ultramafics are diamondiferous metakimberlites. The inferred tectonic (arc) setting makes the emplacement of the so-called Proterozoic diamondiferous metakimberlites unlikely, if we are to go by the Clifford's Rule. However, if these ultramafic rocks are really metakimberlites and the source of the diamonds, then the Clifford's Rule may not be applicable in the Ghanaian situation, and the Birim field may be one of the few exceptions to this general rule. This would, then, present a typical example of subduction zone related diamondiferous kimberlites. Keywords: Birim Diamondiferous field, Birimian, geochemistry, Ghana, tectornc settingAfrican Journal of Science and Technology Vol. 5(2) 2004: 9-1