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Cancer cell lines are used in many biomedical research laboratories. Why, then, are they often described as unrepresentative of the cells from which they were derived? Here, I argue that they have been unjustly accused. Under the right conditions, and with appropriate controls, properly authenticated cancer cell lines retain the properties of the cancers of origin.
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Clinical research has previously lacked good methodology and much opinion was based on anecdote which is widely regarded as the weakest form of clinical evidence. There are few randomised control trials in orthodontics which support or refute areas of dogma. The number of randomised control trials is increasing significantly. There is currently however no good evidence that orthodontics causes or cures temporomandibular joint dysfunction, that appropriate extractions in orthodontics ruin patients' profiles, or that the orthodontist is able to significantly influence facial growth with appliances.
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Since its discovery by Erspamer in the 1930s and identification by Page in the 1950s, 5-HT (5-hydroxytryptamine; serotonin) has been an elusive candidate as a substance that plays a role in the disease of high blood pressure, also known as hypertension. In both animal and human hypertension, arterial contraction to 5-HT is profoundly enhanced. Additionally, 5-HT is a vascular smooth muscle cell mitogen. Because both increased arterial contractility and smooth muscle growth contribute to the disease of hypertension, it is logical to believe that 5-HT is a potential cause of disease, and thus a foe. However, decades of research have produced conflicting results as to the potential role of 5-HT in hypertension. This review will discuss historical findings which both support and refute the involvement of 5-HT in hypertension, and pose some new questions that may reveal novel ways for 5-HT to modify vascular control of blood pressure.
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BACKGROUND: Fundoplication is commonly complicated by belching difficulty and abdominal bloating. Postoperative belching ability, however, is difficult to assess; subjective patient reporting is often used but may be unreliable. Manometric measurement of the gastro-oesophageal 'common cavity' is an objective marker of gastro-oesophageal gas reflux. METHODS: Twenty patients who had undergone Nissen fundoplication and 11 healthy controls underwent oesophageal manometry at rest and during gastric distension for 10 min with 750 ml of gas. RESULTS: Half of the patients reported an inability to belch; the other half reported varying degrees of belching difficulty, most of whom were rarely able to relieve bloating by belching. During gastric distension, none of the patients had transient lower oesophageal sphincter relaxation, while the controls had a median of 1 (range 0-1). Patients had fewer common cavities than controls; however, none of the belch urges experienced during gastric distension in patients was associated with a common cavity, compared with 48 per cent in controls. CONCLUSION: After fundoplication, patients do not belch as a result of gastro-oesophageal gas reflux; rather it may be due to oesophagopharyngeal reflux of swallowed air. Subjective reporting of belching ability is inaccurate and manometric measurement of common cavities provides a better means of assessment.
Advanced robotic surgery was first introduced into urology in 2000. The first studies showed the feasibility and safety of the daVinci (Intuitive Surgical Inc., Sunnyvale, CA) telemanipulator assistance in radical prostatectomy, pelvi-ureteric junction obstruction, and radical cystectomy and neobladder formation. The miniature endowristed tools offer a potential advantage over standard laparoscopy in the accuracy of preparation and suturing. Other features are a three-dimensional vision system and unimpaired hand-eye coordination. Complex laparoscopic tasks are learned faster by using the robot, which may also explain the shorter training required for radical prostatectomy than for manual laparoscopy. This new and expensive technology has spread rapidly over the last 4 years. By 2004, approximately 10% of radical prostatectomies in the USA will be robot-assisted. Data on the functional and oncological outcomes are accruing but not yet conclusive. There will be a further spread of robotic surgery, routine telesurgery, smaller and more affordable systems, the introduction of virtual reality, all developments which have the potential to urological surgeons to improve.
Fifteen years ago, an experimental effort to magnify a myocardial infarction, with preinfarction episodes of transient ischemia, proved paradoxically protective. In the ensuing years, surgeons have learned to discriminate a biochemical/metabolic/functional spectrum of cardiac states ranging from healthy myocardium to "stunned" or "hibernating" heart to the modes of "apoptotic" or "necrotic" cardiomyocyte death. It is now clear that "protective cardiac preconditioning" influences all of these cardiac states. The cellular mechanisms of preconditioning (PC) are now sufficiently understood to permit clinical application. Ligation of adrenergic, adenosine, bradykinin or opioid receptors involves signaling via both tyrosine and calcium-dependent protein kinases (PKC), which activate mitochondrial ATP-dependent potassium channels. Subsequently, the release of oxygen radicals induces nuclear translocation of transcriptional regulators, which transform the cardiomyocyte into a more resilient cell. Although preconditioning was initially recognized as protecting only against infarction, PC also limits postischemic dysrhythmias and enhances contractile function. Phase I (safety) and phase II (efficacy) clinical trials now persuasively support pharmacological preconditioning as a safe mode of preventing postcardiac surgical complications. Indeed, preconditioning is currently being proposed as adjunctive to hypothermic perfusates in protecting against the obligate organ ischemia during transplantation.
AIMS: Since as far back as 1980, SIOP (Société Internationale d>>Oncologie Pédiatrique) have advocated primary nephrectomy (PN) only for unilateral renal tumours in patients </=6 months of age. Patients aged 7-12 months have been pre-treated with chemotherapy before nephrectomy is performed. The aims of this study were: (1) to evaluate how the SIOP guidelines for infants 0-6 months and 7-12 months of age were followed in three Dutch centres for Paediatric Oncology before and after 1980, and (2) to carry out an inventory of the incidence of benign tumours in this patient population below 12 months of age. METHODS: Retrospective analysis of 67 patients under 12 months of age (1969-1995) with a unilateral renal tumour at diagnosis was carried out. Demographics, pathology, staging and treatment variables were analysed. RESULTS: Of 67 patients, 39 were male and 28 female. Twenty-six (39%) infants were 0-6 months of age (group A) and 41 (61%) were 7-12 months old (group B). In group A there were five patients (19%) with congenital mesoblastic nephroma (CMN), out of which one was still-born and therefore received no treatment, and 21 patients with a unilateral Wilms>> tumour (WT). Fourteen of the 25 patients (56%) were treated with PN, including four patients with CMN. In group B there was one patient (2%) with CMN and 40 patients with WT. Thirteen of the patients (31%) were treated with PN. A total of 15 patients were treated before 1980 and 26 after 1980. Eight of 15 (53%) patients were treated with PN before 1980 and 21/26 (81%) were pre-treated after 1980, according to the protocol. CONCLUSION: Despite the SIOP recommendations, only 56% of patients </=6 months were treated with PN. The percentage of pre-treated patients in group B increased after changing the protocol in 1980 to 81%. In the age group included in the SIOP studies the protocol had been used significantly more often compared to the group included in the guidelines only. The known excellent survival rate justifies a primary nephrectomy approach in the youngest age group, however, in cases of a large tumour, pre-operative chemotherapy in reduced doses may still be considered. In our study fewer CMN were found (19%) than reported in the SIOP studies (20-70%), most likely due to a low registration rate, as a consequence of excluding this very young age group (0-6 months) from the SIOP protocol.
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