Stereotactic Image-Guided Intensity Modulated Radiotherapy Using the HI-ART II Helical Tomotherapy System

The highly integrated adaptive radiation therapy (HI-ART II) helical tomotherapy unit is a new radiotherapy machine designed to achieve highly precise and accurate treatments at all body sites. The precision and accuracy of the HI-ART II is similar to that provided by stereotactic radiosurgery systems, hence the historical distinction between external beam radiotherapy and stereotactic procedures based on differing precision requirements is removed for this device. The objectives of this work are: (1) to describe stereotactic helical tomotherapy processes (SRS, SBRT); (2) to show that the precision and accuracy of the HI-ART meet the requirements defined for SRS and SBRT; and (3) to describe the clinical implementation of a stereotactic image-guided intensity modulated radiation therapy (IG-IMRT) system that incorporates optical motion management.     

Activity of the de novo engineered antimicrobial peptide WLBU2 against Pseudomonas aeruginosa in human serum and whole blood: implications for systemic applications

Cationic amphipathic peptides have been extensively investigated as a potential source of new antimicrobials that can complement current antibiotic regimens in the face of emerging drug-resistant bacteria. However, the suppression of antimicrobial activity under certain biologically relevant conditions (e.g., serum and physiological salt concentrations) has hampered efforts to develop safe and effective antimicrobial peptides for clinical use. We have analyzed the activity and selectivity of the human peptide LL37 and the de novo engineered antimicrobial peptide WLBU2 in several biologically relevant conditions. The host-derived synthetic peptide LL37 displayed high activity against Pseudomonas aeruginosa but demonstrated staphylococcus-specific sensitivity to NaCl concentrations varying from 50 to 300 mM. Moreover, LL37 potency was variably suppressed in the presence of 1 to 6 mM Mg(2+) and Ca(2+) ions. In contrast, WLBU2 maintained its activity in NaCl and physiologic serum concentrations of Mg(2+) and Ca(2+). WLBU2 is able to kill P. aeruginosa (10(6) CFU/ml) in human serum, with a minimum bactericidal concentration of <9 microM. Conversely, LL37 is inactive in the presence of human serum. Bacterial killing kinetic assays in serum revealed that WLBU2 achieved complete bacterial killing in 20 min. Consistent with these results was the ability of WLBU2 (15 to 20 microM) to eradicate bacteria from ex vivo samples of whole blood. The selectivity of WLBU2 was further demonstrated by its ability to specifically eliminate P. aeruginosa in coculture with human monocytes or skin fibroblasts without detectable adverse effects to the host cells. Finally, WLBU2 displayed potent efficacy against P. aeruginosa in an intraperitoneal infection model using female Swiss Webster mice. These results establish a potential application of WLBU2 in the treatment of bacterial sepsis.     

Classification of diabetes mellitus

Diabetes mellitus affects almost 16 million Americans. It has become a major public health problem and the number one cause of adult blindness, end-stage renal disease, and nontraumatic amputations in the United States. It also markedly increases the risk for cardiovascular, cerebrovascular, and peripheral artery disease. The resultant increased morbidity and mortality results in a cost from diabetes of almost $100 billion annually in the United States. Studies like the UK Prospective Diabetes Study have noted that a substantial percentage of patients with newly diagnosed diabetes already have evidence of microvascular and macrovascular complications of the disease. This indicates that diabetes began in these individuals many years before it was diagnosed. By reducing the diagnostic glycemic threshold for diabetes and recommending regular screening of individuals at increased risk, the ADA hopes that patients will have diabetes diagnosed earlier, before the occurrence of complications and at a time when appropriate treatment can reduce the long-term complications, adverse clinical outcomes, and impaired quality of life that today afflict so many diabetic individuals.     

Health-Related Anxiety and Hypochondriacal Concerns in Medical Students: A Cross-Sectional Study From Pakistan

Phenomenon: Transient health-related anxiety/hypochondriacal concerns in medical students are well documented. The literature suggests that after studying a particular disease, medical students are likely to consider any symptoms earlier regarded as normal to be signs of the disease they are studying. The aim of this study was to investigate the prevalence of these phenomena and their cognitive and distress aspects among medicals students in Karachi, Pakistan. Approach: This was an analytical, cross-sectional study. Self-administered questionnaires comprising demographic details, the Short Health Anxiety Inventory, Medical Students’ Disease (MSD) Perception Scale, and MSD Distress Scale were distributed to 1st- through 5th-year medical students. Findings: In total, 513 medical students (66% female) participated. Their mean age was 21 ± 1.6 years. Three hundred seventy-five students (73%) reported having visited a doctor at least once in the past 6 months. Fifty students (9.9%) admitted to having addictions. The overall prevalence of significant hypochondriacal concerns was 11.9% (61 students). The presence of addiction was associated with a greater likelihood of developing significant health-related anxiety (odds ratio = 3.82, p = .003), 95% confidence interval [1.51, 7.11]. Age, gender, medical school, year of medical school, and visits to the doctor in the previous 6 months were not associated with greater likelihood of developing significant health-related anxiety. Second-year medical students experienced a significantly greater degree of worry (MSD–Distress scale) than 5th-year students (M score = 12.6 ± 4.6 vs. 10.7 ± 4.4, p = .04). Insights: The prevalence of substantial hypochondriacal concerns in medical students in Pakistan was low in comparison to similar studies published in literature. Student health physicians should be aware of the true prevalence of hypochondriacal concerns and behavior and not dismiss legitimate complaints. Educational sessions to counteract this phenomenon can be incorporated into the curriculum of undergraduate medicine. By defining heightened awareness of symptoms as a normal process, different coping techniques can be discussed to help medical students reduce their level of stress.     

Clinicopathologic characteristics and steroid response of IgM nephropathy in children presenting with idiopathic nephrotic syndrome

There is no detailed information on clinical and immunopathologic features of immunoglobulin M nephropathy (IgMN) in children with idiopathic nephrotic syndrome (INS) in Pakistan. We reviewed our native renal biopsies over 15 years (July 1995-July 2010) and identified 135 cases of IgMN in nephrotic children (≤17 years). Their demographic, clinical and immunopathologic data were retrieved from biopsy reports and case notes. Mean age of this cohort was 7.6 ± 4.2 years. Males were 92 (68.1%) and females were 43 (31.9%). Steroid-dependent NS was seen in 88 (65.2%) cases and steroid-resistant NS in 47 (34.2%). Hematuria was found in 42 cases (31.2%) and hypertension in 27 (19.5%). The most common morphologic change was glomerular mesangial proliferation, found in 89 (65.9%) biopsies. Minor changes were seen in 46 (34.1%) cases and focal segmental glomerulosclerosis (FSGS) in 37 (27.4%). Immunofluorescence microscopy showed diffuse mesangial positivity of IgM in all cases. C3 and C1q were found in 72 (53.3%) and 40 (29.7%) cases, respectively. Our results show that IgMN is a fairly common cause of INS in children in Pakistan. It shows a spectrum of morphologic changes ranging from minor changes to FSGS.     

Laparoscopic Cholecystectomy in Cirrhotic Patients

Background and Objectives:

Gallstones are twice as common in cirrhotic patients as in the general population. Although laparoscopic cholecystectomy (LC) has become the gold standard for symptomatic gallstones, cirrhosis has been considered an absolute or relative contraindication. Many authors have reported on the safety of LC in cirrhotic patients. We reviewed our patients retrospectively and assessed the safety of LC in cirrhotic patients at a tertiary care hospital in Pakistan.

Methods:

From January 2003 to December 2005, a retrospective study was conducted at SU IV, Liaquat University of Medical & Health Sciences Jamshoro. All the cirrhotic patients with Child-Pugh class A and B cirrhosis undergoing LC were included in the study. Cirrhosis was diagnosed based on clinical, biochemical, ultrasonography, and intraoperative findings of the nodular liver and histopathological study.

Results:

Of 250 patients undergoing laparoscopic cholecystectomy, 20 (12.5%) were cirrhotic. Of these 20, 12 (60%) were Childs group A and 8 (40%) were group B. Thirty percent were hepatitis B positive, and 70% were hepatitis C positive. Preoperative diagnosis of cirrhosis was possible in 80% of cases, and 20% were diagnosed during surgery. Morbidity rate was 15% and mortality rate was 0%. Two patients developed postoperative ascites, and mean hospital stay was 2.8±0.1 days. Of the 20 cases, 2 (10%) were converted to open cholecystectomy. The mean operation time was 70.2±32.54 minutes.

Conclusion:

Laparoscopic cholecystectomy is an effective and safe treatment for symptomatic gallstone disease in select patients with Child-Pugh A and B cirrhosis. The advantages over open cholecystectomy are the lower morbidity rate and reduced hospital stay.     

Nocistatin attenuated the nociceptin induced c-Fos expression in the mouse hippocampus

Nocistatin and nociceptin/orphaninFQ (N/OFQ) are the two new peptides which may have roles in nociception, memory, anxiety, and other biological functions. Nocistatin acts as a functional antagonist to N/OFQ in several functions, but their neuro-anatomical sites of interaction are unknown. We investigated the effect of combined intracerebroventricular (i.c.v.) injection of nocistatin with N/OFQ, on N/OFQ induced c-Fos expression in the mouse hippocampus, using c-Fos immunohistochemistry. We found that co-injection of nocistatin with N/OFQ significantly attenuated N/OFQ induced c-Fos expression in the hippocampus.     

Presence of NGAL/MMP-9 complexes in human abdominal aortic aneurysms

It has been suggested that the intraluminal thrombus of abdominal aortic aneurysms (AAAs) predisposes for AAA enlargement and rupture. The growth of the AAA is dependent on proteolytic degradation of elastin. Here, we analysed whether the neutrophil gelatinase-associated lipocalin (NGAL) is expressed within the thrombus and the aneurysm wall. NGAL can bind to metalloproteinase-9 (MMP-9) and inhibit its degradation, thereby preserving enzymatic activity. Biopsies were obtained from thrombus-free and thrombus-covered aneurysm wall and the intraluminal thrombus from patients undergoing elective surgery for AAA. Immunohistochemistry and real-time PCR were used to study NGAL and MMP-9 expression. Immunoprecipitation, gel zymography, Western blot and ELISA were used to detect and quantify NGAL/MMP-9 complexes. NGAL was detected in the thrombus, the interface between the thrombus and the underlying wall and in the wall itself. Double staining showed that neutrophils are the major source of NGAL expression. Immunoprecipitation of MMP-9 with antibody against NGAL showed that complexes of NGAL and active MMP-9 were present in thrombus, the interface fluid and the aneurysm wall. Western blot analyses using non-reducing conditions and gel zymography demonstrated that high-molecular-weight complexes of NGAL/MMP-9 were present within the different regions. The concentration of the NGAL/MMP-9 complex was highest in the luminal part of the thrombus. In conclusion, NGAL in complex with activated MMP-9 is present in AAA wall and thrombus. Neutrophil-derived NGAL could enhance the proteolytic activity associated with AAA, but the importance of this mechanism for aneurysm growth remains to be shown.