The temporal order judgment paradigm: subcortical attentional contribution under exogenous and endogenous cueing conditions.

The role of subcortical attentional processing was investigated under exogenous and endogenous cueing conditions. As retinotectal projections arise predominantly from the nasal retina i.e., temporal hemifield, subcortical attention should be distributed asymmetrically under monocular viewing conditions with a temporal hemifield advantage. We compared the results of monocular and binocular viewing conditions using a temporal order judgment (TOJ) paradigm. Subjects fixated a centrally located cross and two stimuli were presented with a variable onset asynchrony. Three experiments were conducted: no cue, exogenous cue and endogenous cue. Subjects reported which stimulus seemed to appear first. An effect consistent with subcortical processing was found under exogenous cueing conditions. No such effect was found under endogenous cueing conditions. We believe that subcortical attentional processing in response to an exogenous cue facilitates rapid shifts in attention towards environmental stimuli. We found no evidence for subcortical processing in voluntary directed attention and believe this process to be cortical in nature.     

Anion gap among patients of multiple myeloma and normal individuals

OBJECTIVE: To compare the Anion gap between patients of multiple myeloma and normal individuals presenting at a tertiary care hospital. DESIGN AND METHODS: This is a matched case-control study conducted at Aga Khan University Hospital, Karachi, from July 10, 2004 to April 30, 2006. The anion gap (AG) from the medical records of the 82 diagnosed cases of multiple myeloma (MM) and 104 controls were compared. Immunoglobulins (IgG and IgA) were measured by array nephelometric assay. Staging for MM patients were performed based on Salmon-Durie method. AGs were compared by independent sample t-test. Pearson coefficient of correlation was used to correlate paraprotein IgG concentration and anion gap. RESULTS:: Of the 186 study subjects (82 cases and 104 controls), 70% were males and 30% were females. The mean ages of MM and controls were 59.68+/-11.94 and 60+/-9.2 years respectively. There was a significant difference in mean AG, 11.2+/-1.7 mmol/L in control group (p<0.001) compared to 6.8+/-4.6 mmol/L for IgG MM and 8.4+/-4.37 mmol/L for IgA MM patients. Multiple myeloma patients stratified by clinical stages had anion gap of 8.7+/-1.7 in stage I, 7.93+/-0.47 in stage II and 5.65+/-0.31 in stage III. A significant correlation was found in IgG myeloma when anion gap was expressed as a function of the serum monoclonal protein concentration. CONCLUSION: The anion gap is significantly lower in multiple myeloma patients compared to controls. Lowered anion gap is more specific feature of the IgG type MM. We suggest that correlation of AG with the disease severity and with paraproteins concentration could potentially be useful in monitoring patients for disease progression. However, longitudinal studies are required to confirm the utility of anion gap in monitoring patients with MM.     

Induction of procalcitonin and proinflammatory cytokines in an anhepatic baboon endotoxin shock model

Our objective was to evaluate the role of the liver for procalcitonin (PCT) and cytokine induction in a baboon endotoxin shock model. Complete liver resection with portocaval anastomosis was established in a baboon prior to the induction of endotoxin shock by intravenous administration of endotoxin (100 microg/kg LPS Escherichia coli). Two baboons without surgical intervention were used as controls. Plasma concentrations of PCT, tumor necrosis factor (TNF)-alpha, interleukin (IL) 6, IL-8, endotoxin, and hemodynamic and metabolic parameters were measured pre- and postoperatively and until 6 h after endotoxin administration. PCT concentrations increased to 1.2 and 4.6 ng/mL in control animals at 6 h, but remained below 0.3 ng/mL in the anhepatic baboon. IL-6 and IL-8 increased only for few hours in controls, but remained elevated in the hepatectomized animal near their maximum (IL-6, 2-6 ng/mL) or several-fold higher (IL-8, 30-35 ng/mL), whereas TNF-alpha response was only a small fraction (0.3 ng/mL) of the controls. Endotoxin was much higher and longer persisting in the hepatectomized animal compared with controls. The near absence of PCT production in the anhepatic baboon suggests a primary role for the liver as a source of PCT production during endotoxin shock. Furthermore, the liver also seems to be an important source of TNF-alpha, but not IL-6 or IL-8.     

Performance of TechLab C. DIFF QUIK CHEK and TechLab C. DIFFICILE TOX A/B II for the detection of Clostridium difficile in stool samples

Two membrane-bound enzyme immunoassays by TechLab, Blacksburg, VA, were evaluated and compared with the Triage Micro C. difficile Panel (Biosite Diagnostics, San Diego, CA), with culture, and with cytotoxic assay. The TechLab panels were C. DIFF QUIK CHEK (QC-GDH) and C. DIFFICILE TOX A/B II (QC-toxinA/B), which detect glutamate dehydrogenase (GDH) and Clostridium difficile toxins A and B, respectively. The Triage Panel detects GDH (TR-GDH) and toxin A (TR-toxinA). METHODS: Stool samples were inoculated onto CCFA plates (Q-Labs, Quebec, Canada) after alcohol shock, and suspected colonies were identified by the MicroScreen C. difficile latex slide agglutination test (Microgen Bioproducts, Surrey, UK). TR-GDH, TR-toxinA, QC-GDH, and QC-toxinA/B tests were performed according to the manufacturers' instructions on all the samples. Samples positive for GDH or culture but negative for TR-toxinA and QC-toxinA/B were further tested by cytotoxin assay (CTA). CTA was also performed on samples that caused blackening of the Triage Micro C. difficile Panel. RESULTS: A total of 313 of 401 stool samples were negative for GDH and toxins (78%). Eighty-eight samples were positive either for GDH or culture or both. Thirteen of these could not be evaluated for C. difficile-associated diarrhea (CDAD) because CTA test was not performed. Toxin/s was detected at least by one method in 46 (11.8%) of 388 samples that were positive for culture or GDH and were considered diagnostic of CDAD. The QC-GDH was more sensitive than culture and TR-GDH for the detection of C. difficile. However, in 18GDH-positive samples positive for either of the Triage or TechLab immunoassays, the culture remained negative. Ten (2%) results of the Triage immunoassays could not be evaluated because of discoloration of the panels. QC-GDH (93.5%) was more sensitive for detecting the presence of toxin-producing C. difficile than TR-GDH (79.5%). TR-toxinA was more specific for detecting the presence of toxin-producing C. difficile than QC-toxinA/B (100% and 96.9%, respectively). CONCLUSIONS: The GDH tests had a faster turnaround time than the traditional culture methods. QC-GDH was most sensitive for the detection C. difficile-positive stools and was easy to use.     

Metabolic syndrome: treatment of hypertensive patients

Metabolic syndrome (MetSyndr), a constellation of abnormalities [obesity, glucose intolerance, insulin resistance (IR), dyslipidemia (low HDL-cholesterol, high LDL-cholesterol and triglycerides (TG)], and elevated blood pressure (BP)], increases the risk of cardiovascular (CV) disease and premature death. From 10% to 30% of the adult population in industrialized countries has MetSyndr, which effectively predicts the development of type 2 diabetes mellitus (T2D) and CV disease. Because of the complex etiology of MetSyndr, a multi-targeted, integrated therapeutic approach is required to simultaneously treat high BP, obesity, lipid disorders and T2D (if present), to fully protect CV, cerebrovascular and renal systems. If lifestyle modification (weight control, diet, exercise, smoking cessation, moderation of alcohol intake) is ineffective, pharmaco-theraphy should be added to treat simultaneously the lipid- and non-lipid CV risk factors.Patients with HTN and MetSyndr should be started on angiotensin-converting enzyme (ACE) inhibitors, unless contraindicated. The ACE inhibitors and angiotensin receptor blockers (ARBs) reduce the odds of developing new onset T2D and also decrease albuminuria. The ACE inhibitors provide cardioprotective and renoprotective benefits beyond their effect on BP; they also improve IR. The ARBs are renoprotective in addition to being cardioprotective. Long-acting calcium channel blockers are also recommended in hypertensive patients with MetSyndr; these drugs also improve IR. Thiazides (at low doses) and selected ss-blockers can be given to patients with HTN and MetSyndr. Celiprolol in combination with diuretics has a favorable effect on glucose tolerance and IR in patients with HTN and MetSyndr, and spironolactone added to ACE inhibitor or ARB therapy provides additional reno- and CV protective benefits in patients with diabetic nephropathy. Carvedilol, a ss-blocker with vasodilating properties, added to ACE inhibitor or ARB therapy, is effective in preventing worsening of microalbuminuria in patients with HTN and MetSyndr; it also improves IR and glycemic control. Most patients eventually require two or more antihypertensive drugs to reach BP goal. It is recommended that therapy in patients whose BP is more than 20/10 mm Hg above target at diagnosis be initiated with a combination of antihypertensive drugs, administered either as individual drugs or as fixed-dose formulations. Treatment with fixed-dose combinations, such as irbesartan + hydrochlorothiazide provides good BP control in more than two-thirds of hypertensive patients with MetSyndr. Lipid and BP targets are reached in a high percent of patients with HTN and CV disease treated with a combination of amlodipine + atorvastatin.In conclusion, hypertensive patients with the MetSyndr be treated aggressively for each component of the syndrome to provide CV, cerebrovascular and renal protection.