Serum insulin-like growth factor-1 is an independent predictor of prognosis in patients with renal cell carcinoma

Obesity is associated with an increased risk of certain cancers, including renal cell carcinoma. A possible mediator of this risk is insulin-like growth factor-1 (IGF-1). The authors evaluated the prognostic information of IGF-1, IGFBP-3, leptin, and prealbumin in sera sampled at diagnosis from 256 consecutive patients with renal cell carcinoma. Insulin-like growth factor-1 and leptin were positively correlated to body mass index (BMI). Insulin-like growth factor-1 and IGFBP-3 did not correlate to tumour stage or grade. Leptin and prealbumin were both inversely related to tumour stage and grade. When survival was analysed in patients with levels above a median of IGF-1, leptin, and prealbumin, prognosis was more favourable, compared with those with lower levels (p=0.017; p=0.024, and p<0.0001, respectively). In a multivariate analysis, tumour stage and serum IGF-1 levels were independent prognostic factors. The results indicate that serum IGF-1 at diagnosis is related to prognosis in renal cell carcinoma.     

Inadequacy of standard screen resolution for localization of seizures recorded from intracranial electrodes

Seizures recorded during long-term monitoring with implanted intracranial electrodes are typically interpreted by visual inspection alone by using digital display systems. When high-frequency activity is digitized and displayed on a typical monitor, it is altered in ways that are not always appreciated and that may have an impact on the intracranial EEG (ICEEG) interpretation. We describe a case of a neocortical-onset seizure in which false localization occurred with a 12-s per screen display. Because frequencies in excess of 100 Hz are not uncommon in neocortical seizures, at most 4 to 5 s of EEG, depending on the screen resolution, data-sampling rate, and other factors, should be displayed at one time during visual interpretation to localize the seizure onset. Alternatively, spectral analysis should be performed on recordings of neocortical seizures to detect high-frequency activity that may be missed on visual inspection.     

STRIDE 1: effects of the selective ET(A) receptor antagonist, sitaxsentan sodium, in a patient population with pulmonary arterial hypertension that meets traditional inclusion criteria of previous pulmonary arterial hypertension trials

Sitaxsentan (SITAX; Thelin, Encysive Corporation, Bellaire, TX, U.S.A.) is a highly selective oral endothelin-A receptor antagonist. STRIDE-1, a 12-week randomized, doubleblind, placebo-controlled trial of sitaxsentan for pulmonary arterial hypertension showed significant benefit in 6-minute walk distance, functional class and hemodynamics. Pulmonary arterial hypertension clinical trials traditionally limit enrolment to class III/IV patients with idiopathic pulmonary arterial hypertension or pulmonary arterial hypertension related to connective tissue disease, who have a baseline 6-minute walk distance of < 450 m. In contrast, STRIDE-1 included milder cases: class II patients, no baseline 6- minute walk cut-off, and congenital heart disease patients. We now present the STRIDE-1 subset who would have qualified under traditional inclusion criteria. The results were: change for placebo (mean +/- SE) vs change for sitaxsentan (mean +/- SE) vs treatment effect (mean), all statistically significant: 6-minute walk (m): -26 +/- 13, 39 +/- 10, 65; mean right atrial pressure (mmHg): 2.1 +/- 0.8, -1.2 +/- 0.5, -3.3; mean pulmonary arterial pressure (mmHg): 0.4 +/- 1.5, -4.7 +/- 1.5, -5.1; cardiac index (L/min per m): -0.09 +/- 0.09, 0.38 +/- 0.06, 0.47; pulmonary vascular resistance (dyne.s.cm): 85 +/- 60, -274 +/- 47, -359. A 45% improvement in functional class was seen in sitaxsentan-treated patients (P = 0.0005). Thus, in the STRIDE-1 subpopulation that met enrolment criteria of previous pulmonary arterial hypertension trials, improvement in efficacy parameters with sitaxsentan therapy was even greater than seen in the entire STRIDE-1 population.     

Single-isomer drugs: true therapeutic advances

Chirality is one of the main features of biology, and many of the processes essential for life are stereospecific, meaning that one out of two or more isomers may work best in a particular physiological situation. Could this be used in drug development and result in any clinical relevance and true therapeutic advance? There are occasions when the development of one of the isomers might be expected to be advantageous: for example, only one of the isomers may be active, only one of the isomers may cause adverse effects, or one of the isomers may have more advantageous pharmacological properties. As an example of the last, the successful development of esomeprazole will be described. Before the introduction of esomeprazole, the proton pump inhibitor omeprazole was the standard treatment for gastric acid-related diseases, such as gastro-oesophageal reflux disease. A serious type of gastro-oesophageal reflux disease is erosive oesophagitis, an increasingly common condition that may lead to life-threatening complications. Doubling the standard dose of omeprazole from 20 to 40 mg did not improve healing rates (74% versus 75%), and thus a substantial proportion of patients remained unhealed with standard treatment. The (S)-isomer of omeprazole, esomeprazole, was shown to heal more patients than omeprazole as a result of unique metabolic properties that clearly differentiates esomeprazole from omeprazole, the racemate. At comparable doses, these properties lead to several clinical advantages: higher bioavailability in extensive metabolisers (the majority of patients), lower exposure in poor metabolisers, less interindividual variation and a steeper dose-response curve at steady state resulting in a more pronounced inhibition of gastric acid secretion. Esomeprazole has been studied clinically for a variety of acid-related conditions, showing that the compound is as well tolerated and more effective with regard to healing and symptom relief than the recommended treatment with omeprazole. Thus, from this example it is clear that the exploration and development of single-isomer drugs may bring significant advances in treatment options.     

Spasticity in a child with myelomeningocele treated with continuous intrathecal baclofen

Patients with myelomeningocele may often suffer from severe spasticity. Surgical treatment of the underlying pathology such as hydromyelia and tethered cord may be successful, but failures are not uncommon. Those cases may offer a surgical challenge since further therapeutic options are limited. We present the case of a 7-year-old boy with myelomeningocele and related conditions suffering from severe spasticity and pain in his lower limbs. Surgical efforts with untethering and posterior fossa decompression failed to improve the symptoms. A test with 25 microg intrathecally delivered baclofen showed a total relief of spasticity and pain so that a pump for continuous baclofen delivery was implanted. During 32 months of follow-up, his spasticity has been under excellent control on 55-157 microg baclofen per day. Continuous delivery of intrathecal baclofen may be a surgical option to consider in patients with myelomeningocele and severe spasticity.     

Perinatal outcome following third trimester exposure to paroxetine

BACKGROUND: Paroxetine hydrochloride is commonly used for maternal depression, panic disorder, and obsessive-compulsive disorder. The drug readily crosses the human placenta. Although it does not appear to increase teratogenic risk, there have been case reports of neonatal withdrawal. Symptoms were described soon after birth and lasted up to 1 month. OBJECTIVE: To investigate whether there is a clinically important discontinuation syndrome in neonates exposed to paroxetine in utero. METHODS: Prospective, controlled cohort study. PATIENTS: Fifty-five pregnant women counseled prospectively by the Motherisk program in Toronto, Ontario, regarding third-trimester exposure to paroxetine and their infants were included in the study group. Pregnant women who discontinued paroxetine before the third trimester or those receiving other drugs known to cause withdrawal-type symptoms, such as opioids or benzodiazepines, were excluded. A comparison group of 27 women using paroxetine during the first or second trimester and 27 women using nonteratogenic drugs were matched for maternal age, gravity, parity, social drug use, and nonteratogenic drug use. RESULTS: Of the 55 neonates exposed to paroxetine in late gestation, 12 had complications necessitating intensive treatment and prolonged hospitalization. The most prevalent clinical picture was respiratory distress (n = 9), followed by hypoglycemia (n = 2), and jaundice (n = 1). The symptoms disappeared within 1 to 2 weeks. In the comparison group, only 3 infants experienced complications (P =.03). In logistic regression, only third-trimester exposure to paroxetine was associated with neonatal distress (odds ratio, 9.53; 95% confidence interval, 1.14-79.3). CONCLUSION: When used near term, paroxetine is associated with a high rate of neonatal complications, possibly caused by its common discontinuation syndrome.     

Detection of human papillomavirus in sanitary napkins: a new paradigm in cervical cancer screening

Human papillomavirus was successfully detected by polymerase chain reaction (PCR) in menstrual blood or vaginal discharge collected in sanitary napkins in 100% of 17 women having koilocytosis, cervical intraepithelial neoplasia, or squamous carcinoma. We advocate this form of cervical cancer screening because of its high sensitivity and acceptance by patients.     

Discrepancies between ordered and delivered concentrations of opiate infusions in critical care

OBJECTIVES: We sought to test the assumption that the measured concentrations of medication infusions are within pharmaceutical standards (+/-10% of intended concentrations) and whether, at the time the infusion was mixed, the professional background of persons preparing the infusion or the unit for which the infusion was prepared were related to the observed variation. DESIGN, SETTING, AND PARTICIPANTS: This prospective, observational study was conducted in the neonatal and pediatric intensive care units of a university-affiliated tertiary pediatric center. Morphine infusions prepared for clinical use were randomly sampled over a 7-month period. Those with no error between labeled and ordered concentration were further analyzed. High-performance liquid chromatography was used to determine the concentration of morphine infusions. The primary outcome was a difference of >10% between ordered and measured concentrations. MEASUREMENTS AND MAIN RESULTS: The measured concentration of 65% of the 232 infusions was >10% different from the ordered concentration (95% confidence interval, 58-71%). The concentrations of 6% of infusions represented two-fold errors (95% confidence interval, 3-9%). The difference was normally distributed around zero, suggesting a cumulative effect of random errors, rather than a systematic bias. The time that the infusion was prepared, the professional background of the persons preparing the infusion, and the unit for which the infusion was mixed were not significant predictors of discrepancy (p =.74, analysis of variance). CONCLUSIONS: The concentration of two thirds of infusions prepared for clinical use was outside accepted industry standards. These findings are likely to be broadly representative of intravenous drug administration in hospitalized children and pediatric pharmacokinetic studies. Further study of the causes and clinical impact is required.