First report of disseminated Mycobacterium skin infections in two liver transplant recipients and rapid diagnosis by hsp65 gene sequencing

We present here the first report of disseminated skin Mycobacterium infections in two liver transplant recipients, in which hsp65 gene sequencing was used for rapid species identification. Both patients had hepatitis B virus-related cirrhosis and diabetes mellitus and presented with progressive generalized, nodular skin lesions. In one patient, a 50-year-old woman who had frequent contact with marine fish, an acid-fast bacillus was isolated from skin biopsy tissue after 2 months of culture. While awaiting phenotypic identification results, hsp65 gene sequencing showed that it was most closely related to that of Mycobacterium marinum with 100% nucleotide identity. The patient was treated with oral rifampin, ethambutol, and moxifloxacin. In the other patient, a 59-year-old woman, direct PCR for Mycobacterium using hsp65 gene from skin biopsy tissue was positive, with the sequence most closely related to that of M. haemophilum with 100% nucleotide identity. Based on PCR results, the patient was treated with clarithromycin, ethambutol, moxifloxacin, and amikacin. A strain of M. haemophilum was only isolated after 3 months. Skin lesions of both patients resolved after 1 year of antimycobacterial therapy. Nontuberculous Mycobacterium infections should be considered in liver transplant recipients presenting with chronic, nodular skin lesions. This report highlights the crucial role of hsp65 gene PCR and sequencing on both cultured isolates and direct clinical specimens for rapid diagnosis of slow-growing Mycobacterium infection.     

Variability in the Manifestation of Pre‐excited Atrial Fibrillation: Its Quantification,Theoretical Origin,and Diagnostic Potential

Background: Irregular broad complex tachycardia (BCT) may be due to atrial fibrillation (AF) occurring in the presence of ventricular pre‐excitation (pre‐excited AF) or bundle branch block (BBB‐AF). While irregularity is a defining characteristic of AF. it is a common subjective impression that greater variability in manifestation exists for pre‐excited AF than BBB‐AF. This difference can potentially be exploited for distinguishing the two conditions it some means can be found to quantify it. Methods: For each of 75 ECGs showing irregular BCT (41 pre‐excited AF and 34 BBB‐AF), a random sample of 10 distinct QRS complexes were selected for quantitative measurement of variability in manifestation, which included the standard deviation (SD) of the width, the SD of the axis, and the coefficient of variation (CV) of the amplitude of the QRS complex. Results: Pre‐excited AF showed statistically significantly greater values than BBB‐AF with respect to these measures, and receiver‐operating characteristic curves showed that these differences could be useful for their discrimination. For the SD of QRS width, a cut‐off value of 8 ms appeared optimal (sensitivity 1.00 and specificity 0.79). For the SD of QRS axis, a cut‐off value of 2.5 degrees appeared optimal (sensitivity 0.84 and specificity 0.56). For the CV of QRS amplitude, a cut‐off value of 0.10 appeared optimal (sensitivity 0.82 and specificity 0.76). Conclusions: Pre‐excited AF demonstrated greater variability than BBB‐AF in manifestation. The measures of variability developed can potentially be useful for diagnosing irregular BCT in practice, especially in the context of automated computer‐aided diagnosis. A.N.E. 2001;6(2):117–122     

Severe rhabdomyolysis associated with the cerivastin-gemfibrozil combination therapy: report of a case.

Cerivastatin is the new 3rd-generation of the synthetic 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitors, the 1st drugs of choice for treating hypercholesterolemia. A potent inhibitor of HMG-CoA reductase, it possesses a high affinity for liver tissue and decreases plasma low-density lipoprotein cholesterol at microgram doses. Cerivastatin produces reductions in low-density lipoprotein cholesterol of 31.3% and 36.1% at doses of 0.3 and 0.4 mg/day, respectively It is an uncomplicated agent with regard to its pharmacokinetic profile, low potential for interaction with other drugs, and suitability for use in those with impaired renal function. Most other statins have been implicated in causing rhabdomyolysis, either as monotherapy or in combination with other agents. We report what to our knowledge is the most profound case yet in the literature of rhabdomyolysis in association with cerivastatin-gemfibrozil combination therapy, in regard both to the extreme elevation in serum creatinine kinase and to the patient's near-paralytic weakness.     

Low levels of cell cycle inhibitor p27kip1 combined with high levels of Ki-67 predict shortened disease-free survival in T1 and T2 invasive breast carcinomas

Breast cancer is the second leading cause of cancer death in North American women. There is considerable need for better prognostic markers to identify those subsets of patients who would benefit from more aggressive therapy because their tumors show an increased risk of poor clinical behavior. p27kip1 is an important inhibitor of the cell cycle that acts by binding and inactivating cyclin-dependent kinases (CDKs). The aim of this study was to determine the prognostic value of loss of p27 protein in invasive breast cancer. We performed an immunohistochemical study of 147 patients with T1 and T2 invasive breast cancers and compared survival in the high p27 expressing group with that of the low p27 expressing group. On univariate analysis comparing tumor size, nodal status, Ki-67, c-erbB-2, p53 and estrogen receptor, low or absent p27kip1 is a strong predictor of reduced disease-free survival. Importantly, on multivariate analysis, the combined effect of low p27 with high Ki-67 is a stronger predictor of reduced disease-free survival than either marker alone. This simple, reliable and inexpensive assay, particularly when used in combination with Ki-67, improves the ability to predict disease recurrence and could become a useful adjunct of breast cancer evaluation to better identify high risk patients.     

The Meaning-Making intervention (MMi) appears to increase meaning in life in advanced ovarian cancer: a randomized controlled pilot study

Objective: This pilot study aimed to provide supportive evidence for the acceptability and usefulness of the Meaning‐Making intervention (MMi) in patients newly diagnosed with Stage III or IV ovarian cancer, and to provide estimates of parameters needed to design a full‐scale study. Methods: A randomized controlled trial with 24 patients (12 experimental and 12 control) was conducted. Existential well‐being (primary outcome), overall quality of life, distress, anxiety, depression and self‐efficacy were measured. Results: Compared to the control group, patients in the experimental group had a better sense of meaning in life at one and three months post‐intervention. Conclusion: The MMi seems a promising intervention for advanced cancer patients, and a full randomized controlled trial is warranted to further investigate its efficacy. Copyright © 2010 John Wiley & Sons, Ltd.     

Regulation of glutamate transporters in astrocytes: Evidence for a relationship between transporter expression and astrocytic phenotype

The astrocytic glutamate transporters, EAAT1 and EAAT2, remove released L-glutamate from the synaptic milieu thereby maintaining normal excitatory transmission. EAAT dysfunction during the excitotoxicity and oxidative stress of neurological insults may involve homoeostatic mechanisms associated with astrocytic function. We investigated aspects of EAAT function and expression in concert with astrocytic phenotype in primary cultures of cortical astrocytes and mixed cells of the spinal cord. In spinal cord mixed cultures, hydrogen peroxide (300 microM) reduced both EAAT activity and cellular viability to half of their basal values at 24 h post-treatment, but at 2 h EAAT activity was unaltered, while cellular viability was significantly decreased, suggestive of a mechanism for the maintenance of EAAT activity. Cytochemistry for MAP2, GFAP and propidium iodide revealed that neurons and astrocytes were damaged in a time-dependent manner. A change in astrocyte morphology was observed, with astrocyte cell bodies becoming larger and processes becoming more stellate and often shorter in length. EAAT1 immunoreactivity was reduced at 24 h post-treatment and a re-distribution of the protein was noted after 2 h treatment. In pure astrocytes, lipopolysaccharide (1 microg/ml, 3 d) increased [3H]D-aspartate uptake by 90%, as well EAAT1 immunoreactivity and astrocyte stellation, as shown by immunofluorescent labelling for GFAP. In both culture systems, prominent changes were noted in EAAT function and localization in conjunction with altered astrocytic phenotype. Our findings are indicative of a relationship between astrocytic phenotype and the level of EAAT activity that may be a vital component of astrocytic homeostatic responses in brain injury.     

A role for CNS α-2 adrenergic receptors in opiate-induced muscle rigidity in the rat

A number of potential neurochemical mediators of opiate-induced muscle rigidity have been proposed based on the results of systemic drug studies and on knowledge of the brain sites implicated in opiate rigidity. The effects of i.c.v. pretreatment with selected opioidergic, α adrenergic and serotonergic drugs on muscle rigidity induced with systemic injection of the potent opiate agonist alfentanil (ALF) were investigated in spontaneously ventilating rats. The opiate antagonist methylnaloxonium (MN; 0.2–14 nmol), α-2 adrenergic agonists dexmedetomidine (DEX; 0.4–42 nmol) or 2-(2,6-diethylphenylamino)-2-imidazoline hydrochloride (ST91; 4–400 nmol), α-1 adrenergic antagonist prazosin (PRZ; 7–70 nmol) or serotonergic antagonist ketanserin (KET; 18–550 nmol) were injected i.c.v. (10 μl) and ALF (500 μg/kg s.c.) was administered 10 min later. S.c. electrodes were used to record gastrocnemius electromyographic activity. Both MN and DEX dose-dependently and potently antagonized ALF-induced rigidity. ST91 produced shorter-lived, less profound, antagonism of ALF rigidity. PRZ, at the highest dose tested, produced a delayed and modest reduction in ALF rigidity. A large, non-selective, dose of KET incompletely attenuated ALF rigidity. These results lend support to the hypothesis that central opioid and α-2 adrenergic receptors mediate opiate-induced muscle rigidity in the rat.