Quinine for leg cramp: time to call a halt?

The MURCS association is traditionally regarded as a disorder limited to the female sex. It has been hypothesized that men displaying the combination of azoospermia, segmentation abnormalities of the cervicothoracic spine and renal anomalies may have a male analogue of MURCS. Here we describe a patient with non-obstructive azoospermia and Klippel-Feil anomaly type II and suggest that this may represent another case of 'MURCS in the male'.     

Assessment of safety-critical specifications

Formal methods can reduce the ambiguity in specifications and provide a basis for verification later on-especially important for safety-critical systems. The author compares specifications in the software cost reduction method and in the Vienna Definition Method for a safety-critical system and identifies several key assessment issues: understandability, assessment criteria, and semantic capabilities     

The trials and tribulations of a robotic screening core

It is well recognized within the pharmaceutical industry that high throughput screening is a valuable and rapid tool to identify novel chemical compounds that may lead to tomorrow''s drugs. High throughput screening involves testing as many chemical compounds as quickly as possible against a defined molecular or cellular ‘target’ (for example an enzyme) in the hope that interacting compounds may provide significant therapeutic benefits.At Wyeth-Ayerst Research, a Robotics and Automation Research Core Group has been established which serves as the in-house resource for high throughput screening. The robotics group has three missions: (1) develop and perform high throughput screens for customers in all therapeutic departments in the company; (2) educate customers in issues related to screen design; and (3) help customers to bring automated workstations into their laboratories. The mission, therefore, requires the effective use of automation, as well as building a strong collaboration with customers.The challenges that have been faced fall into two categories: technology limiting and customer relations. Technological challenges arise because it is necessary to develop and implement assays with very different formats and biochemical endpoints within extremely shortened time frames. The primary means to meet these challenges is with flexible robotics and flexible people. Challenges in the area of customer relations include setting realistic expectations, maintaining a sense of collaboration (and not merely service), educating investigators as to how to deal with the huge amount of data generated and seeking feedback. Effective and frequent communication, and an awareness of each individual''s perspective, are essential to provide the most appropriate service.     

Rise in erythropoietin concentrations in experimental Trypanosoma congolense infection of calves

A bioassay was used to measure erythropoietin (EPO) concentrations in calves with haemorrhagic anaemia due to blood loss and in calves with anaemia due to Trypanosoma congolense infection. The bioactivity of EPO was measured in the assay by its stimulatory effect on 125I-deoxyuridine incorporation in spleen cells from phenylhydrazine-treated mice. Erythropoietin concentrations in blood-volume-depleted calves were elevated 6 h after blood loss, maximal (1225 mU/ml) at 33 h and below detection limits at 72 h. Reticulocytes (0.05 +/- 0.1%) appeared in blood by 72 h, peaked at 120 h and disappeared from the circulation by 7 days after bleeding. The packed cell volume (PCV) started increasing at 120 h and reached near pre-bleeding values by 14 days. In T. congolense-infected calves, parasites were first detected in the peripheral blood 12 days post-infection (dpi). Parasitaemia peaked (5 x 10(5) trypanosomes/ml of blood) at 15-18 dpi and, thereafter, several waves of parasitaemia were observed, but the peaks gradually diminished. Undiluted plasma from T. congolense-infected calves suppressed 125I-deoxyuridine incorporation into spleen cells from 13 dpi onwards. The suppressive effect of plasma was partly negated by five-fold dilution, which made possible the detection of increased EPO concentrations during the acute and chronic stages of the anaemia. The highest EPO peaks, reaching 2300 mU/ml in one calf, were detected during the chronic stage of the infection. At 15-39 dpi, there was a transient bone-marrow erythropoietic response characterized by an increase in mean corpuscular volume and a decrease in mean corpuscular haemoglobin concentration but with few reticulocytes (0.4%). However, from 76 dpi onwards, this response waned despite low PCV and elevated EPO concentrations. These results suggest that there is an ineffective erythroid response in the face of elevated EPO concentrations during bovine trypanosomiasis. The negative effect of plasma and serum from trypanosome-infected calves on the in-vitro bioactivity of EPO suggests the presence of inhibitory factors.     

Clinical applications of composite and realtime megavoltage imaging

The versatility of electronic portal imaging devices (EPIDs) is best demonstrated by their ability to perform novel megavoltage imaging protocols, which are still pertinent to good radiotherapy practice. This paper examines two such techniques: composite and realtime imaging. Our EPID can be programmed to acquire and manipulate images very easily, allowing images from segmented treatment protocols to be mixed and displayed, giving a composite image of the effective treatment result. Its use for verifying the efficacy of spinal shielding using a segmented, offset collimator technique is described. By acquiring images very quickly, realtime imaging sequences can be obtained and used to analyse anatomical movement within a single treatment field. The technique is employed here to investigate movement in radical lung, breast, abdomen, pelvis and thyroid treatments. Our results show that the protocol is vital for treatment sites involving the lungs; changes up to 5 mm have been observed in the maximum lung depth for breast treatments, and displacements up to 16 mm for radical lung treatments. It is also useful in other anatomical sites for ensuring that no movement occurs.     

Pharyngeal flap necrosis as a cause of airway obstruction during induction of anesthesia

Anesthesiologists should approach the airway carefully in the patient with a diagnosis of head and neck carcinoma, particularly if the patient has had previous surgery and reconstruction. Patients with head and neck carcinoma may be difficult intubations due to altered anatomy from the tumor or fibrotic changes because of radiation therapy. Our patient had had pharyngectomy and reconstruction with a pectoralis major skin flap. The patient returned to the operating suite for wide-excision pharyngectomy and had acute airway obstruction after induction of general anesthesia. The pectoralis flap had necrosed, pulling away from the pharyngeal wall and obstructing the patient's glottic opening.     

Creatine supplementation and exercise performance: an update

Creatine, a natural nutrient found in animal foods, is alleged to be an effective nutritional ergogenic aid to enhance sport or exercise performance. Research suggests that oral creatine monohydrate supplementation may increase total muscle creatine [TCr], including both free creatine [FCr] and phosphocreatine [PCr]. Some, but not all, studies suggest that creatine supplementation may enhance performance in high-intensity, short-term exercise tasks that are dependent primarily on PCr (i.e., < 30 seconds), particularly laboratory tests involving repeated exercise bouts with limited recovery time between repetitions; additional corroborative research is needed regarding its ergogenic potential in actual field exercise performance tasks dependent on PCr. Creatine supplementation has not consistently been shown to enhance performance in exercise tasks dependent on anaerobic glycolysis, but additional laboratory and field research is merited. Additionally, creatine supplementation has not been shown to enhance performance in exercise tasks dependent on aerobic glycolysis, but additional research is warranted, particularly on the effect of chronic supplementation as an aid to training for improvement in competitive performance. Short-term creatine supplementation appears to increase body mass in males, although the initial increase is most likely water. Chronic creatine supplementation, in conjunction with physical training involving resistance exercise, may increase lean body mass. However, confirmatory research data are needed. Creatine supplementation up to 8 weeks has not been associated with major health risks, but the safety of more prolonged creatine supplementation has not been established. Creatine is currently legal and its use by athletes is not construed as doping.