Effect of methylphenidate on vital signs and adverse effects in adults with traumatic brain injury

OBJECTIVE: To study methylphenidate's adverse effects and impact on vital signs within the adult traumatic brain injury population. DESIGN: Thirty-five adults with traumatic brain injury enrolled in a double-blind, placebo-controlled, 6-wk crossover study of methylphenidate, given in a dose of 0.3 mg/kg/dose, twice a day. Vital signs were taken by trained clinicians and research assistants. Participants filled out weekly questionnaires pertaining to the adverse effects. RESULTS: Poor appetite was the only adverse effect related to methylphenidate. Other adverse effects commonly associated with methylphenidate, such as insomnia, rapid heart rate, and anxiety, were not found to be significantly related to the medication. The average rise in mean arterial pressure on methylphenidate was 2.5 mm. Methylphenidate showed a stronger impact on pulse, with an average increase of 7 beats/min. Baseline vital signs did not predict the degree of increase on methylphenidate. CONCLUSION: Methylphenidate appears to be safe for the adult population with traumatic brain injury. However, because a few individuals experienced significant changes in vital signs and adverse effects, all patients should be monitored.     

Effects of methylphenidate on attention deficits after traumatic brain injury: a multidimensional, randomized, controlled trial

OBJECTIVE: To evaluate the effects of methylphenidate on a variety of aspects of attention, ranging from laboratory-based impairment measures to caregiver ratings and work productivity, in individuals after traumatic brain injury. DESIGN: A total of 34 adults with moderate to severe traumatic brain injury and attention complaints in the postacute phase of recovery were enrolled in a 6-wk, double-blind, placebo-controlled, repeated crossover study of methylphenidate, administered in a dose of 0.3 mg/kg/dose, twice a day. A wide range of attentional measures was gathered weekly, including computerized and paper-and-pencil tests of attention, videotaped records of individual work in a distracting environment, real-time observational scoring of attentiveness in a classroom environment, and caregiver and clinician rating scales of attentiveness. Participants also attempted to guess their drug condition each week. Data from the first ten participants were used for pilot purposes, to develop attentional factors for composite scoring, and to identify attentional dimensions suggestive of a treatment effect for independent replication. The remaining 24 participants' results were used to confirm potential treatment effects seen in the pilot sample, using Wilcoxon's signed-ranks test on composite factor scores and individual variables. RESULTS: A total of 54 dependent variables were reduced to 13 composite factors and 13 remaining individual variables. Of the 13 attentional factors, five showed suggestive treatment effects in the pilot sample. Of these, three showed statistically significant treatment effects in the replication sample: speed of information processing (effect sizes, -0.06 to 0.48; P < 0.001), attentiveness during individual work tasks (effect sizes, 0.15-0.62; P = 0.01), and caregiver ratings of attention (effect sizes, 0.44-0.50; P = 0.01). Of the individual variables, four showed suggestive treatment effects in the pilot sample, but only one showed significant treatment effects in the replication sample: reaction time before errors in the Sustained Attention to Response Task (effect size, 0.20; P = 0.03). No treatment-related improvement was seen in divided attention, sustained attention, or susceptibility to distraction. None of the variables showed suggestive or definite negative treatment effects. Effect sizes for those performance measures positively affected by methylphenidate were in the small to medium range and included both impairment and activity level measures. Improvements in processing speed did not seem to come at the expense of accuracy. CONCLUSIONS: Methylphenidate, at 0.3 mg/kg/dose, given twice a day to individuals with attentional complaints after traumatic brain injury, seems to have clinically significant positive effects on speed of processing, caregiver ratings of attention, and some aspects of on-task behavior in naturalistic tasks. Further research is needed to identify the optimal dose and to extend these findings to less carefully selected individuals.     

Guidelines for improving care in respiratory disease in the UK

More than eight million people in the UK have respiratory conditions and one in four people die from them. We appear to be facing a major paradox with regard to the management of respiratory disease in the UK. Although we have a wide range of diagnostic tests and effective treatments at our disposal, we do not appear to be making any impact on the morbidity and mortality of respiratory disease. Respiratory disease needs to be moved onto the 'must do' agenda.     

Use of verapamil as a potential P-glycoprotein inhibitor in a patient with refractory epilepsy

OBJECTIVE: To describe a patient in whom we used adjunctive verapamil therapy was used for its P-glycoprotein inhibitory effects. CASE SUMMARY: Verapamil was added to the antiepileptic drug regimen of a 24-year-old woman with intractable epilepsy. The average time interval between hospitalizations for complex partial status doubled. The addition of verapamil greatly improved overall seizure control and subjective quality of life in this pharmacoresistant patient. DISCUSSION: The overexpression of P-glycoprotein in the central nervous system may be one mechanism of pharmacoresistance in patients with epilepsy. The calcium-channel blocker verapamil is a known inhibitor of P-glycoprotein and may function to block P-glycoprotein-modulated efflux of antiepileptic drugs in the brain, thereby raising the intracellular concentration of antiepileptic drugs and ultimately decreasing seizure burden in patients with refractory epilepsy. CONCLUSIONS: Verapamil may offer pharmacoresistant patients hope of improved seizure control due to its potential P-glycoprotein inhibitory effects.     

Effects of short-term fenoldopam infusion on gastric mucosal blood flow in septic shock

BACKGROUND: Inadequate splanchnic perfusion in septic shock is associated with increased morbidity and mortality. As result of splanchnic ischemia, mucosal permeability increases. Considering the implication of improved mucosal perfusion in terms of maintenance of mucosal barrier integrity, dopamine-1 receptor stimulation could be helpful in septic shock. The goal of the current study was to determine the effects of fenoldopam on systemic hemodynamic parameters and gastric mucosal perfusion in patients with septic shock. Furthermore, the authors tested the hypothesis that the addition of fenoldopam (0.1 microg x kg(-1) x min(-1)) to a combination of norepinephrine and dobutamine (5 microg x kg(-1) x min(-1)) may improve gastric mucosal perfusion in septic shock. METHODS: Patients with septic shock were randomized to a double-blind 2-h infusion of fenoldopam (n = 20) or placebo (n = 20). Each group received dobutamine (5 microg x kg(-1) x min(-1)), and the dosage of norepinephrine was adjusted to achieve a mean arterial pressure between 70 and 80 mmHg. A laser-Doppler probe and tonometer were introduced into the gastric lumen. RESULTS: A significant increase in gastric mucosal perfusion, detected by laser-Doppler flowmetry, was observed in the group treated with fenoldopam (P < 0.05). In addition, this increase in microcirculatory flow occurred despite the fact that systemic flow remained unchanged. Differences in gastroarterial partial pressure of carbon dioxide values were not statistically significant in the fenoldopam and placebo groups. CONCLUSIONS: The study showed that, for the same mean arterial pressure, short-term fenoldopam infusion increased gastric mucosal perfusion in patients with septic shock.     

Sentinel node staging of resectable colon cancer: results of a multicenter study

OBJECTIVE AND SUMMARY BACKGROUND DATA: Sentinel lymph node (LN) sampling, a technique widely used to manage breast cancer and melanoma, seeks to select LNs that accurately predict regional node status and can be extensively examined to identify nodal metastatic disease not detected by standard histopathological staging. For patients with resectable colon cancer, improved identification of LN disease would significantly advance patient care by identifying patients likely to benefit from adjuvant therapy. This study, conducted by 25 surgeons at 13 institutions, examined whether sentinel node (SN) sampling accurately predicted LN status for patients with resectable colon cancer. METHODS: SN sampling involved peritumor injection of 1% isosulfan blue, followed by identification of all LN visualized within 10 minutes. SN sampling was performed on 79 of 91 patients enrolled, followed by multilevel sectioning (MLS) of the nodes and examination by a single study pathologist. RESULTS: By standard histopathology, 7 patients had primary disease that was either benign or not colon cancer and were therefore excluded from further studies. Of 72 colon cancer cases studied, 48 (66%) were node-negative and 24 (33%) contained nodal metastases. SNs were successfully located in 66 cases (92%), with an average of 2.1 nodes per patient. SNs were negative in 14 of 24 node-positive cases (58%). MLS revealed tumor in a SN in 1 of these cases, bringing the false-negative rate of SN examination to 54%. CONCLUSION: This multi-institutional study found that for patients with node-positive colon cancer, SN examination with MLS failed to predict nodal status in 54% of cases. We conclude that SN sampling with MLS, used alone, is unlikely to improve risk stratification for resectable colon cancer.     

Operative laparoscopy in the management of perforated peptic ulcer

The aim of this retrospective study was to assess the feasibility, safety and efficacy of the laparoscopic approach in the management of perforated peptic ulcers. From January 1997 to December 2002, all patients referred to our community hospital for abdominal surgical emergencies were routinely managed by laparoscopic surgery. A review was carried out on 39 consecutive patients suffering from perforated peptic ulcers with or without generalised peritonitis. The study population comprised 24 male and 15 female patients, aged 30 to 94 years (mean age: 62 +/- 18). Laparoscopic repair was attempted in all patients. Laparoscopy afforded the correct diagnosis in all cases. Laparoscopic peritoneal washout (irrigation and suction of the entire abdominal cavity) with simple suture of the perforation proved successful in 34 patients. An additional omental patching was performed in 15 of these cases. Conversion to conventional open surgery was necessary in 5 patients. The morbidity and mortality rates were 13% and 10%, respectively. The mean operative time was 77 minutes (range: 40-120) and the mean hospital stay 9 days (range: 3-22). Laparoscopic repair of perforated ulcers is technically feasible but requires sound experience in laparoscopic abdominal emergencies. This study shows that the mini-invasive procedure is safe and effective, offering a valid alternative to traditional laparotomy.     

Treatment of acute biliary pancreatitis: our experience

The results of endoscopic and surgical treatment in 21 patients affected by acute biliary pancreatitis are reported. All patients were managed according to the same protocol. Once the diagnosis was formulated (pain, serum amylase, ultrasonography, cholestasis and/or cholangitis) and the severity evaluated (Ranson's criteria, glucose and urea levels), the 21 patients underwent endoscopic retrograde cholangiopanctratography--within 24 hours in 8 patients (predicted severe disease) or within 72 hours in 13 patients (predicted mild disease). Endoscopic sphincterotomy was performed in 18 patients with stones in the common bile duct and was successful in 94.5% (17 patients: 3 patients underwent more than one session to confirm or achieve clearance of the duct). The morbidity rate associated with endoscopic sphincterotomy was 16% (3 patients: 2 haemorrhages, 1 perforation). There were no deaths. Cholecystectomy was performed in 16 patients within 2-9 weeks of the initial attack of acute biliary pancreatitis. There were 3 minor complications (respiratory, laparotomy, urinary infection), no major intraoperative or postoperative morbidity, and no mortality. Acute biliary pancreatitis is still associated with significant morbidity and mortality, but can be managed safely with combined medical, endoscopic and surgical treatment.     

Phytochemical investigations regarding the flavonoidic compounds of some species belonging to the Achillea millefolium L. group

In this study a qualitative and quantitative analysis of flavonoids from flower heads of Achillea species belonging to the A. millefolium L. group was achieved. Rutin, apigenin-7-O-glucoside, luteolin-7-O-glucoside in the methanolic extract of A. collina J. Becker ex Reichenb., A. pratensis Saukel et Langer, A. millefolium L. were determined by comparison of their Rf-TLC data with those obtained from reference flavonoids. Apart from flavonoid glycosides, the free aglycones, apigenin and luteolin were identified by TLC. Flavonoidic compounds have been detected by spectrophotometric method in concentrations of appr. 0.5-1.8% in plant materials.