Online feedback focusing algorithm for hyperthermia cancer treatment.

PURPOSE: Magnetic resonance (MR) imaging is increasingly being utilized to visualize the 3D temperature distribution in patients during treatment with hyperthermia or thermal ablation therapy. The goal of this work is to lay the foundation for improving the localization of heat in tumors with an online focusing algorithm that uses MR images as feedback to iteratively steer and focus heat into the target. METHODS: The algorithm iteratively updates the model that quantifies the relationship between the source (antenna) settings and resulting tissue temperature distribution. At each step in the iterative process, optimal settings of power and relative phase of each antenna are computed to maximize averaged tumor temperature in the model. The MR-measured thermal distribution is then used to update/correct the model. This iterative procedure is repeated until convergence, i.e. until the model prediction and MR thermal image are in agreement. A human thigh tumor model heated in a 140 MHz four-antenna cylindrical mini-annular phased array is used for numerical validation of the proposed algorithm. Numerically simulated temperatures are used during the iterative process as surrogates for MR thermal images. Gaussian white noise with a standard deviation of 0.3 degrees C and zero mean is added to simulate MRI measurement uncertainty. The algorithm is validated for cases where the source settings for the first iteration are based on erroneous models: (1) tissue property variability, (2) patient position mismatch, (3) a simple idealized patient model built from CT-based actual geometry, and (4) antenna excitation uncertainty due to load dependent impedance mismatch and antenna cross-coupling. Choices of starting heating vector are also validated. RESULTS: The algorithm successfully steers and focuses a tumor when there is no antenna excitation uncertainty. Temperature is raised to > or = 43 degrees C for more than about 90% of tumor volume, accompanied by less than about 20% of normal tissue volume being raised to a temperature > or = 41 degrees C. However, when there is antenna excitation uncertainty, about 40% to 80% of normal tissue volume is raised to a temperature > or = 41 degrees C. No significant tumor heating improvement is observed in all simulations after about 25 iteration steps. CONCLUSIONS: A feedback control algorithm is presented and shown to be successful in iteratively improving the focus of tissue heating within a four-antenna cylindrical phased array hyperthermia applicator. This algorithm appears to be robust in the presence of errors in assumed tissue properties, including realistic deviations of tissue properties and patient position in applicator. Only moderate robustness was achieved in the presence of misaligned applicator/tumor positioning and antenna excitation errors resulting from load mismatch or antenna cross coupling.     

Proliferative signaling by store-operated calcium channels opposes colon cancer cell cytostasis induced by bacterial enterotoxins

Guanylyl cyclase C and accumulation of cGMP induced by bacterial heat-stable enterotoxins (STs) promote colon cancer cell cytostasis, serving as a tumor suppressor in intestine. Conversely, capacitative calcium entry through store-operated calcium channels (SOCs) is a key signaling mechanism that promotes colon cancer cell proliferation. The present study revealed that proliferative signaling by capacitative calcium entry through SOCs opposes and is reciprocally coupled to cytostasis mediated by guanylyl cyclase C in T84 human colon carcinoma cells. Elimination of capacitative calcium entry employing 2-aminoethoxydiphenylborate (2-APB), a selective inhibitor of SOCs, potentiated cytostasis induced by ST. Opposition of ST-induced cytostasis by capacitative calcium entry reflects reciprocal inhibition of guanylyl cyclase C signaling. Calcium entry through SOCs induced by the calcium-ATPase inhibitor thapsigargin or the receptor agonists UTP or carbachol inhibited guanylyl cyclase C-dependent cGMP accumulation. This effect was mimicked by the calcium ionophore ionomycin and blocked by 2-APB and intracellular 1,2-bis(o-amino-5,5'-dibromophenoxy)ethane-N,N,N',N'-tetraacetic acid-acetoxymethyl ester (BAPTA-AM), a chelator of calcium. Moreover, regulation by capacitative calcium entry reflected ligand-dependent sensitization of guanylyl cyclase C to inhibition by that cation. Although basal catalytic activity was refractory, ST-stimulated guanylyl cyclase C was inhibited by calcium, which antagonized binding of magnesium to allosteric sites required for receptor-effector coupling. These observations demonstrate that reciprocal regulation of guanylyl cyclase C signaling by capacitative calcium entry through SOCs represents one limb of a coordinated mechanism balancing colon cancer cell proliferation and cytostasis. They suggest that combining guanylyl cyclase C agonists and SOC inhibitors offers a novel paradigm for cGMP-directed therapy and prevention for colorectal tumors.     

Disseminated Strongyloides stercoralis in AIDS: a report from India

We report a fatal case of disseminated strongyloidiasis masquerading clinically as stage IV caecal malignancy diagnosed at post mortem by needle necropsy. The parasite was seen in the smears from CSF, pleural fluid, ascitic fluid, splenic aspirate, lung aspirate and aspirates from caecal area. Enteric organisms like Group D streptococci and candida sp were also associated. We believe that this is the first report of widespread dissemination of S. stercoralis in AIDS from India.     

General obesity and central adiposity in a representative sample of Tehranian adults: prevalence and determinants

AIMS: To determine the prevalence and associations of general and central obesity in adults residing in district 13 of Tehran and to examine the associations of obesity with certain factors. DESIGN: Population-based cross sectional study. SETTING: Tehran, the capital of Iran. SUBJECTS: A total of 9984 subjects (4164 men and 5820 women) aged 20-70 years. METHODS: Demographic data were collected and anthropometric indices including weight, height, and waist and hip circumference were measured, according to standard protocols. Dietary intake was assessed by means of two 24-hour dietary recall forms. To determine the prevalence and association of general and central obesity, the suggested cut-off for Tehranian people, adjusted for their age group, was used. A body mass index (BMI) of > or =24 for men and > or =25 for women was used to determine the characteristic of obesity. Central obesity was determined as a waist-hip ratio (WHR) of > 0.86 for men and WHR > or = 0.78 for women. To determine the associations between general and central obesity and other factors, logistic regression was used. RESULTS: The means of BMI, waist circumference (WC), and WHR were 25.8 +/- 4.1 kg/m2, 88.3 +/- 11.4 cm, and 0.91 +/- 0.07 in men and 27.3 +/- 5.4 kg/m2, 87.5 +/- 12.9 cm, and 0.83 +/- 0.08 in women, respectively. Obesity and central obesity were higher in women than in men; 67% vs. 29% for obesity and 93% vs. 74.1% for central obesity, respectively. Illiteracy (OR = 1.65; 95% CI = 1.13-2.41 in men; OR = 1.87, 95% CI = 1.59-2.21 in women), marriage (OR = 3.84, 95% CI = 3.63-4.29 in men; OR = 3.20, 95% CI = 3.63-4.19 in women), and very low physical activity (OR = 1.35, 95% CI = 1.09-1.53 in men; OR = 1.39, 95% CI = 1.10-1.76 in women) were factors associated with obesity. The risk of being centrally obese for men in the fourth quartile of legumes intake was lower than men in other quartiles (p < 0.05). Women in the first quartile of dairy consumption had the highest risk of being generally and centrally obese (OR = 2.16, 95% CI = 1.72-2.48 for general obesity and OR = 3.01, 95% CI = 2.36-3.67 for central obesity). The risk of obesity for women in the fourth quartile of energy and saturated fatty acid consumption was higher than for those in the first quartile (OR = 2.69, 95% CI = 2.39-3.11 for energy and OR = 1.36, 95% CI= 1.10-1.64 for saturated fatty acids). The risk of being centrally obese was higher for women in the first quartile of protein intake compared with women in the fourth quartile (OR = 1.71, 95% CI = 1.02-2.32). CONCLUSIONS: The results from this national population-based study in Iran show high prevalence of obesity in Tehranian adults. The strong associations between obesity and certain life style factors confirm the necessity of multifactorial intervention.     

FUO due to sarcoidosis-lymphoma syndrome

This is a patient who presented as a fever of unknown origin (FUO) due to sarcoidosis-lymphoma syndrome. In favor of sarcoidosis was an elevated angiotensin-converting enzyme level, hypercalciuria, and bilateral hilar adenopathy on chest x-ray and chest CT. CT-guided biopsy of a hilar node revealed B-cell lymphoma. The differential diagnosis of sarcoidosis versus lymphoma and sarcoidosis-lymphoma syndrome as a cause of fever of unknown origin is discussed in this article.     

Mood disorders in opioid-dependent patients

AIMS: To assess the rate of current mood disorders in opioid-dependent outpatients. DESIGN: Prevalence study of DSM-IV mood disorders. SETTINGS: Private and government clinics. PARTICIPANTS: Five hundred unpaid opioid-dependent patients who had voluntarily sought treatment. MEASUREMENTS: The Research version of structured clinical interview for DSM-IV Axis I Disorders (SCID-I). RESULTS: The mean age of the subjects (487 men and 13 women) was 33.4 years, ranging from 16 to 67. The majority (68.2%) had private sector job and 13.4% were unemployed. The majority (59.8%) had education at the level of primary, guidance or high school and only 3.8% were illiterate. Three hundred and thirty six (67.2%) subjects were diagnosed as having mood disorders. Of the subjects 274 (54.8%) had substance induced depression, 37 (7.4%) major depression, 14 (2.8%) dysthymia, five (1%) depression due to general medical condition, three (0.6%) cylothymia, three (0.6%) bipolar mood disorder type I. None was diagnosed as having bipolar mood disorder type II. Of the participants 319 (63.8%) reported more than 5 years use of opioid. Of the subjects only 16 (3.2%) reported no episode of abstinence and the majority 484 (96.8%) reported one or more episodes of abstinences. About 4.2% (21) reported less than 1 g/day and the majority 86.4% (432) reported between 1 and 5 g/day current use of opioid. CONCLUSION: Due to high rates of mood disorders in opioid-dependent subjects, psychiatric services should be open and accessible to the patients, especially those who voluntarily seek help and treatment.     

European surgical survey of acute pancreatitis--union of diversity

The widely variable nature of acute pancreatitis renders it a challenging disease to manage via standardized approaches. King and Siriwardena present their findings from a survey of European surgical approaches to diagnostic and therapeutic management of severe acute pancreatitis in an attempt to delineate areas of discordance that may help direct future studies. An erratic trend in the management of severe acute pancreatitis is evident despite growing evidence to support several diagnostic and therapeutic procedures as standards of care. On the other hand, areas of discordance largely characterize those currently lacking in adequate literature support underscoring the need to generate randomized studies that will address them.