Hemostatic and Coagulation Profile in Psoriasis: A Hospital-Based case control Study.

Context: Psoriasis is a chronic inflammatory dermatosis associated with an increased risk of cardiovascular disease and atherothrombosis. Aims: This study was conducted to assess the levels of various hemostatic and coagulation parameters in psoriasis and their correlation with disease severity. Settings and Design: This was a hospital-based observational study. Methods and Material: Seventy-five patients with psoriasis and seventy controls were included in the study. History taking, clinical examination, and calculation of Psoriasis Area and Severity Index (PASI) were done. Blood analysis for Platelet count (PC), mean platelet volume (MPV), Vitamin B12, Thrombin Time (TT), Prothrombin time (PT) and Activated partial thromboplastin time (APPT) were done in both groups. Results: MPV which is a marker of inflammation and platelet activation was significantly increased in cases and positively correlated with the disease severity. Vitamin B12 is an important cofactor in homocysteine (Hcy) metabolism and correlates inversely with serum Hcy which is a known atherothrombotic marker. Vitamin B12 levels were significantly decreased in the cases with a significant negative correlation between Vitamin B12 level and PASI. There was also a significant decrease in serum level of PT, aPTT and TT in cases as compared to controls; however they showed no significant correlation with PASI. Conclusions: Inflammation in psoriasis may drive the process of abnormal platelet activation and coagulation abnormalities thus predisposing psoriatic patients to an atherothrombotic state and increasing the cardiovascular risk in psoriatic patients.

Overview of penicillin allergy.

Allergy to penicillin is the most commonly reported antibiotic allergy. However, most patients who report a positive history of a prior reaction to penicillin are not found to be allergic to penicillin upon skin testing. Often, this history is vague or based on a parent's recollection of an event that occurred in the distant past. Avoidance of penicillin based on self-reported allergic history alone often leads to the use of an alternate antibiotic with greater cost or side effect profile. Patients with a negative skin test to both major and minor determinants may generally be given penicillin, with a statistical risk of developing an allergic reaction similar to that observed in the general population. A more cautious approach in these cases where the degree of suspicion is low, an allergic etiology is unproven, or there is a negative skin test, is to do a graded challenge. If the skin test is positive, an alternate antibiotic should be used. If, however, an alternate antibiotic is not available, then desensitization may be performed, but there are limitations to desensitization as well, and tolerance is not permanent. Avoidance of cephalosporins may be recommended in cases of penicillin allergy, but newer generation cephalosporins have demonstrate less cross-reactivity to penicillin than earlier generation ones. Desensitization protocols for cephalosporins are available but not standardized. The mechanisms of antibiotic sensitization are not clearly understood.

Polyethylene glycol in the design of tumor-targetting radiolabelled macromolecules -- lessons from liposomes and monoclonal antibodies.

Radiolabelled macromolecules such as liposomes and monoclonal antibodies (Mab) are attractive agents for tumour-targetting studies. In addition to their potential diagnostic role, they can also provide vital information on the targetting capacity of therapeutic agents. Certainly in the case of liposome development, this ability to track the pharmacokinetics and biodistribution of the agents in a non-invasive fashion has assisted the design and application of therapeutic liposomal agents. A significant limitation of unmodified liposomes and Mab is their tendency to be cleared rapidly from the circulation. The use of polyethylene glycol (PEG) in the formulation of these agents has the capacity to alter their biological behaviour in such a way as to improve their ability to target tumours. In this paper we review the data relating to the use of PEG-modified liposomes and Mab in the context of nuclear medicine studies.

Detection of pelvic lymph node metastases in gynecologic malignancy: a comparison of CT, MR imaging, and positron emission tomography.

OBJECTIVE: Accurate assessment of lymph node status before treatment is critical in the treatment of gynecologic cancers because the 5-year survival and treatment of women is influenced by lymph node involvement. The aims of this study were to investigate the ability of X-ray CT, MR imaging, and (18)F-FDG positron emission tomography (PET) to detect pelvic lymph node metastases by comparing imaging with histopathologic findings after lymph node dissection. MATERIALS AND METHODS: Eighteen patients with gynecologic cancers were studied by all three imaging methods before surgery. The images were initially reviewed with routine diagnostic conditions and then, subsequently, by two observers who were unaware of the clinical and histopathologic findings of the patients. The nodal sites were split into upper (aortic to common iliac bifurcations) and lower (common iliac bifurcations to inguinal ligament) iliac chains. All observers' results were statistically analyzed with specificity, sensitivity, positive and negative predictive values, Fisher's exact test (individual observers) or chi-square test (combined observers), and Cohen's kappa test. RESULTS: Eight of 18 patients had lymph node metastases at histology. Findings of all three modalities agreed in full in only one patient. CT correctly revealed 10 node-negative patients, whereas MR imaging was correct in eight of these patients. (18)F-FDG PET correctly depicted one patient with lymph nodes negative for tumor. CT was the most specific imaging modality (97.0%), with MR imaging and PET rendering values of 90.7% and 77.3%, respectively, but sensitivity of all modalities was low (CT, 48.1%; MR imaging, 53.7%; PET, 24.5%). Observer agreement for each modality was good; kappa values among all observers were 0.88 for CT, 0.85 for MR imaging, and 0.72 for PET. CONCLUSION: CT is the most specific modality for detecting lymph nodes positive for tumor in gynecologic cancers, whereas MR imaging is the most sensitive. The poor results of PET in the pelvis are attributed to urinary (18)F-FDG in the ureters or bladder, which may mask or imitate lymph node metastases.

Clearance kinetics of solutes used to measure glomerular filtration rate.

Agents used to measure glomerular filtration rate (GFR) give a biexponential plasma disappearance curve on multiple peripheral venous sampling between 20 min and 4 h after intravenous injection. These two exponentials are generally regarded to represent equilibration of agent throughout the extracellular fluid (ECF) space and renal clearance, respectively. In seven subjects undergoing diagnostic arteriography, arterial and antecubital venous plasma samples were obtained up to 60 min in five and up to 120 min in two following simultaneous intravenous injection of 99Tcm-diethylene triamine pentaacetate (99Tcm-DTPA) and inulin. The count rate from 99Tcm was simultaneously recorded over the calf with a collimated scintillation probe in five subjects up to 60 min post-injection. The arterial and venous time-concentration curves were interpolated and subtracted to give a curve of the arterio-venous (A-V) concentration difference, which was then integrated. Arterial time-concentration curves display three exponentials, the first of which has the largest amplitude and disappears by about 20 min. The A-V concentration difference becomes zero at about the same time. The integral of the A-V concentration difference, which represents activity in the interstitial space of the forearm, has a time course consistent with the second compartment of a model of two compartments in series (the first being plasma) and a time course that is reciprocally similar to the first exponential of the triexponential arterial plasma curve. The curve externally recorded by scintillation probe has a shape consistent with a signal that is the composite of interstitial 99Tcm-DTPA and plasma 99Tcm-DTPA activities. The arterial plasma clearance curve of GFR agents is triexponential; the first exponential reflects equilibration of agent between plasma and the interstitial space of carcass tissue (mainly muscle and skin). The second exponential is minor compared with the first; it is not clear what it represents. The third exponential reflects renal clearance.

Bidirectional transport of iminodiacetic organic anion analogues between plasma and hepatocyte.

The kinetics of organic anions are well described and back-diffusion from hepatocyte to plasma is accepted. Although iminodiacetic (IDA) analogues, as organic anions, should also show bidirectional transport between hepatocyte and plasma, this has not been directly demonstrated heretofore. The aim of this study was to directly demonstrate back-diffusion and to quantify it in terms of its fractional rate constant. Kinetics of diethyl IDA were studied in three anaesthetised dogs in which femoral arterial and hepatic venous samples were obtained after injection of tracer into (a) a peripheral vein or (b) hepatic artery or portal vein. Arterial time-concentration curves were also compared between peripheral venous and either hepatic arterial or portal venous injections. Time-activity curves were recorded from regions of interest over the cardiac blood pool and peripheral hepatic parenchyma in 30 patients undergoing routine IDA hepatobiliary imaging with diethyl IDA or mebrofenin and fractional rate constants of clearance of IDA from the hepatocyte compared between compartmental and deconvolution analyses. After peripheral injection in dogs, there was an early arteriovenous concentration gradient across the liver indicating an hepatocyte extraction fraction in the three animals of 0.9, 0.8 and 0.6. The net extraction fraction decreased exponentially over 40 min. Time-concentration curves from hepatic vein and femoral artery were virtually superimposed following intrahepatic injections. Peripheral arterial curves, however, had different shapes according to whether injections were intrahepatic or peripheral, and were consistent with significant back-diffusion. In clinical studies, the blood disappearance curves were fitted as the sum of two exponentials and the liver curves as the difference of two exponentials (with rate constants denoted alpha1h and alpha2h). Based on compartmental analysis of the blood curves, the sum of the fractional rate constants of tracer movement from hepatocyte to bile canaliculus (k32) and to plasma (k12) was similar to and correlated with the rate constant, alpha, of the hepatocyte impulse response function (r=0.62, n=30, P<0.001). In contrast, alpha1h and alpha2h were respectively clearly greater and smaller than alpha. Moreover, neither of these hepatic rate constants correlated with alpha. Diffusion of IDA from hepatocyte to blood is significant and even in the presence of normal liver function accounts for about 50% of IDA transport out of the hepatocyte. It should be taken into account in pharmacokinetic studies based on either compartmental or deconvolution analysis.

Comparative kinetics of microvascular inulin and 99mTc-labelled diethylenetriaminepenta-acetic acid exchange.

1. After simultaneous intravenous injection as a mixture, 99mTc-labelled diethylenetriaminepentaacetic acid (99mTc-DTPA; molecular mass 492 Da) and inulin (approximately 6000 Da) gave arterial plasma clearance curves consisting of three exponentials, the time courses of which were not significantly different between the two solutes. 2. The ratio of 99mTc-DTPA to inulin concentration in antecubital venous plasma (normalized to the ratio in arterial plasma at 30 s) was 0.6, significantly less than unity, within 2 min after intravenous injection, but increased to reach unity by 60 min. The minimum concentration ratio of 99mTc-DTPA to inulin in arterial plasma was 0.75 at 4 min, also rising to just above unity at 60 min. 3. The extraction fraction from plasma to interstitial space was higher for 99mTc-DTPA (approximately 0.5) than for inulin (approximately 0.2). For both solutes, the net extraction fraction decreased with time, becoming negative at about 25 min after injection. Thereafter, the net extraction fractions remained negative, between -0.05 and -0.1, and not significantly different between the two solutes. 4. 99mTc-DTPA time-activity curves recorded over the limbs with scintillation probes were biphasic, with an initial phase corresponding closely in time with the first exponential of the arterial 99mTc-DTPA plasma clearance curve. The second phase corresponded in time to the intermediate exponential of the arterial 99mTc-DTPA plasma clearance curve. 5. The time course of net 99mTcm-DTPA extraction fraction across the forearm vascular bed was bi-exponential, with phases corresponding in time with the two phases of the limb uptake curves. 6. Deconvolution analysis of the limb time-activity curves, using the arterial time-concentration curve as the input function, gave bi-exponential 99mTc-DTPA impulse response curves in which the time courses of the exponentials corresponded with the first and intermediate exponentials of the arterial 99mTc-DTPA clearance curve. 7. The bi-exponential nature of the equilibrium of 99mTc-DTPA between vascular and interstitial compartments suggests the presence of two separate functional volumes within the interstitial space. Although 99mTc-DTPA and inulin clearly diffuse at different rates across the endothelium, as would be expected from their disparate sizes, the similarity in the time courses of their initial exponentials and simultaneous equalization of transfer rates (i.e. when net extraction fraction was zero) is consistent with the hypothesis that inulin moves initially into a smaller functional interstitial fluid volume than 99mTc-DTPA. The total distribution volumes, however, are not significantly different between the two solutes.