Corticosteroid treatment of severe, non-responsive Clostridium difficile induced colitis.

Clostridium difficile can cause inflammatory diarrhoea and colitis by disrupting normal colonic flora. Corticosteroids are effective against diarrhoea associated with inflammatory bowel disease, but their effectiveness in treating inflammatory diarrhoea of C difficile has not been reported. In this preliminary report, we describe the use of corticosteroids in a child with severe C difficile diarrhoea and colitis refractory to standard treatments.     

Metaphyseal cones and sleeves in revision total knee arthroplasty: Two sides of the same coin? Complications,clinical and radiological results—a systematic review of the literature

MUSCULOSKELETAL SURGERY - Revision total knee arthroplasty (rTKA) is increasing of relevance in orthopaedic surgeon daily practice and this trend is likely to continue in the years ahead. The aim...     

Endogenous opioid blockade and gonadotropin secretion: role of pulsatile luteinizing hormone-releasing hormone administration in anorexia nervosa and weight loss amenorrhea

In anorexia nervosa alterations in the hypothalamic-pituitary-gonadal unit were previously thought to have been connected to an increase of endogenous opiate tone. The authors tried to prove that the replacement of normal endogenous steroid levels could restore the functional coupling between opiatergic and luteinizing hormone-releasing hormone (LH-RH) neurons in patients with anorexia nervosa. Pulsatile LH-RH therapy has been used to achieve normal ovarian activity. The authors studied gonadotropin levels before and during intravenously (IV) pulsatile LH-RH therapy (50 to 100 ng/kg body weight/90 to 120 minutes) in three anorexia nervosa and two weight loss amenorrhea patients, during both placebo and naloxone administration (2 mg IV bolus plus 4 mg infusion lasting 120 minutes). Before therapy, naloxone administration did not significantly change gonadotropin levels in three out of five patients, while a decrease in gonadotropin levels was observed in the other two subjects. During LH-RH therapy, normal pituitary-gonadal activity was demonstrated and ovulatory cycles were found in all patients. Naloxone administration did not change gonadotropin release during LH-RH therapy. Data could support the hypothesis of either a primitive impairment of LH-RH neurons, or an alteration in central regulation of LH-RH pulsar in anorexia nervosa.     

Effect of pulsatile luteinizing hormone-releasing hormone administration on pituitary-gonadal function in elderly man

The effect of short-term pulsatile LHRH administration was studied in 8 healthy subjects ranging from 60 to 81 yr to see if the decrease of pituitary gonadal function could be in part due to changes in the discharge of LHRH from the hypothalamus. Gonadotropin and testosterone (T) secretion was evaluated two weeks before and during LHRH (122-160 ng/kg bw every 120 min sc) infusion. In addition, a bolus dosage of LHRH (50 mu iv) was given both at the beginning and at the end of pulsatile LHRH administration in order to test gonadotrophs sensitivity. A significant increase in gonadotropin levels from day 0 to day 4 was found, and was followed by a subsequent decrease from day 7 to day 14. A slight significant increase in T levels was observed during LHRH administration (p less than 0.01). LH pulses were identified in 5 out of 8 subjects on day 0. On day 14, all the exogenous LHRH pulses were followed by significant LH bursts. There was not a significant decrease in the pituitary LH responsiveness to LHRH test from day 0 to day 14. Our study seems to indicate that pituitary - gonadal unit in normal elderly men can be modulated by pulsatile administration of LHRH. A pulse frequency of LHRH which is probably similar to the physiological one, could induce a slight increase in T levels via qualitative changes in LH activity. We can assume that clinical changes in gonadal activity might also be connected to some disturbances in endogenous LHRH pulsar.     

Design of Biological Equivalence Programs for Therapeutic Biotechnology Products in Clinical Development: A Perspective

The determination of biological equivalence requires that studies are conducted to establish that two molecules, two formulations, or two dosing regimens, for example, are indistinguishable with respect to safety and efficacy profiles that have been previously established. The criteria that are used to establish biological equivalence will depend on the nature of the change (e.g., molecular, process, formulation), the stage of the development program, the duration of treatment, and the intended clinical indications. Key components of an equivalence program include chemical characterization, in vitro and in vivo bioactivity against reference material, pharmacokinetics, and safety. Special considerations for patient populations, endogenous concentrations, environmental factors, immunogenicity, assay methodology, biochemical identity, pharmacodynamic equivalence, and statistical methodology are discussed. In addition, the role of preclinical in vivo assessments is addressed. Specific case studies provide insight into the varied nature of approaches that are currently employed.     

Azole-resistant Candida albicans prosthetic joint infection treated with prolonged administration of anidulafungin and two-stage exchange with implant of a mega-prosthesis

Fungal prosthetic joint infection (PJI) is a rare but severe complication of artroplasty. We report a case of PJI due to azole-resistant Candida albicans successfully treated with combination of prolonged administration of anidulafungin and two-stage joint exchange with insertion of a mega-prosthesis.     

Characterisation of tissue shrinkage during microwave thermal ablation

Purpose: The aim of this study was to characterise changes in tissue volume during image-guided microwave ablation in order to arrive at a more precise determination of the true ablation zone. Materials and methods: The effect of power (20–80?W) and time (1–10?min) on microwave-induced tissue contraction was experimentally evaluated in various-sized cubes of ex vivo liver (10–40?mm?±?2?mm) and muscle (20 and 40?mm?±?2?mm) embedded in agar phantoms (N?=?119). Post-ablation linear and volumetric dimensions of the tissue cubes were measured and compared with pre-ablation dimensions. Subsequently, the process of tissue contraction was investigated dynamically during the ablation procedure through real-time X-ray CT scanning. Results: Overall, substantial shrinkage of 52–74% of initial tissue volume was noted. The shrinkage was non-uniform over time and space, with observed asymmetry favouring the radial (23–43 % range) over the longitudinal (21–29%) direction. Algorithmic relationships for the shrinkage as a function of time were demonstrated. Furthermore, the smallest cubes showed more substantial and faster contraction (28–40% after 1?min), with more considerable volumetric shrinkage (>10%) in muscle than in liver tissue. Additionally, CT imaging demonstrated initial expansion of the tissue volume, lasting in some cases up to 3?min during the microwave ablation procedure, prior to the contraction phenomenon. Conclusions: In addition to an asymmetric substantial shrinkage of the ablated tissue volume, an initial expansion phenomenon occurs during MW ablation. Thus, complex modifications of the tissue close to a radiating antenna will likely need to be taken into account for future methods of real-time ablation monitoring.     

Experimental characterisation of the thermal lesion induced by microwave ablation

Purpose: This work focuses on the characterisation of the ablated area induced by a microwave thermal ablation (MTA) procedure. An experimental methodology for establishing a straightforward correlation between the temperature gradient and the changes in the dielectric properties of the tissue is presented and discussed. Materials and methods: Temperature measurements were performed during an ablation procedure in ex vivo bovine liver, at different distances from the antenna, whereas measurements of complex permittivity were conducted in sagittal sections of the ablated samples. The measured temperatures and dielectric properties were then correlated to obtain the dependence of the dielectric properties’ spatial variation on the temperature gradient. The obtained correlation has been validated through comparison with previously obtained experimental data. A weighted cubic polynomial function and a weighted sigmoid function have been tested for best-fit interpolation of the measured data. Results: Temperatures in the range 23–105?°C were measured during the MTA procedure, while, after the end of the MTA trials, relative permittivities in the range 7–43 and electric conductivities in the range 0.3–1.8?S/m were measured according to the distance from the antenna’s axis. The polynomial function showed better regression coefficients than the sigmoid one for both the relative permittivity (R^2?=?0.9947 versus R^2?=?0.9912, respectively) and the conductivity (R^2?=?0.9919 versus R^2?=?0.9866, respectively). However, the weighted cubic function showed an unrealistic behaviour for the relative permittivity at temperatures lower than 40?°C. Conclusions: According to the results obtained, information on the changes in the dielectric properties of the tissue under MTA treatment could be inferred from measured temperature data. Once validated by in vivo studies, the proposed methodology could be exploited to develop predictive tools for treatment planning.