Single Fraction versus Multiple Fraction Radiotherapy for Palliation of Painful Vertebral Bone Metastases: A Prospective Study

Context:

Metastatic bone disease is a commonly encountered problem in oncology practice. The most useful and cost effective treatment is radiotherapy (RT). Different fractionation schedule of RT can be used to treat such condition.

Aims:

Assessment of pain response in patients with vertebral bone metastasis after treating them with various radiation fractionations and to compare the toxicity profile in the treatment arms.

Settings and Design:

A prospective randomized study was designed to include total 64 patients from July 2010 to May 2011. Patients with histopathologically proven primary malignancy having symptomatic secondary deposits to vertebra were selected for the study. Patients were randomized to two arms receiving multiple fraction of RT with 30 Gy in 10 fractions and 8 Gy in single fraction RT, respectively.

Materials and Methods:

Patients with age >75 years, Karnofsky Performance Status (KPS) <40, features of cord compression were excluded from study. Initial pain response was assessed using Visual Analogue Scale (VAS) and compared using the same scale at weekly interval up to 1 month after treatment completion.

Results:

Arm A comprised of 33 patients while 31 patients were enrolled in Arm B. Baseline patient characteristics were comparable. Eleven patients were lost to follow-up. Initial pain scores were 7.23 ± 0.765 and 7.51 ± 0.55 in arm A and arm B, respectively. Pain scores reduced significantly in both the arms after 1 month (4.39 ± 1.82 in arm A; 5.25 ± 2.39 in arm B). Time of initiation of pain response was earlier in arm A (P = 0.0281), statistically significant. Mild G-I toxicity was noted in both the arms but differences in two arms were not statistically significant (P = 0.49), no interruption of treatment was required because of side effects.

Conclusions:

Different fractionation of radiation has same response and toxicity in treatment of vertebral bone metastasis. Single fraction RT may be safely used to treat these cases as this is more cost effective and less time consuming. Studies may be conducted to find out particular subgroup of patients to be benefitted more by either fractionation schedule; however, our study cannot comment on that issue.     

Hyperbranched poly(NIPAM) polymers modified with antibiotics for the reduction of bacterial burden in infected human tissue engineered skin

The escalating global incidence of bacterial infection, particularly in chronic wounds, is a problem that requires significant improvements to existing therapies. We have developed hyperbranched poly(NIPAM) polymers functionalized with the antibiotics Vancomycin and Polymyxin-B that are sensitive to the presence of bacteria in solution. Binding of bacteria to the polymers causes a conformational change, resulting in collapse of the polymers and the formation of insoluble polymer/bacteria complexes. We have applied these novel polymers to our tissue engineered human skin model of a burn wound infected with Pseudomonas aeruginosa and Staphylococcus aureus. When the polymers were removed from the infected skin, either in a polymer gel solution or in the form of hydrogel membranes, they removed bound bacteria, thus reducing the bacterial load in the infected skin model. These bacteria-binding polymers have many potential uses, including coatings for wound dressings.     

Minimally invasive approaches to the management of pancreatic pseudocysts: review of the literature

Although one third or more of pancreatic pseudocysts might resolve spontaneously, interventional therapy is required for most. Several minimally invasive management approaches are now available, including percutaneous drainage under radiologic control, endoscopic transpapillary or transmural drainage, and laparoscopic internal drainage. This paper reviews the methodology, applications, advantages, shortcomings, and results of these management approaches. A computerized search was made of the MEDLINE, PREMEDLINE, and EMBASE databases using the search words pancreatic and pseudocysts and all relevant articles in English Language or with English abstracts were retrieved. In addition, cross-references from the identified articles were reviewed. Percutaneous drainage is best applied to pseudocysts complicated with secondary infection and in critically ill patients or those unfit for surgery. Radiologic drainage, however, risks the introduction of secondary infection and the formation of an external pancreatic fistula, and is associated with high recurrence rates. Endoscopic transpapillary drainage is beneficial for pseudocysts that communicate with the pancreatic duct and when a dependent drainage could be established. Endoscopic transmural (transgastric or transduodenal) drainage offers good results in the management of suitably located pseudocysts that complicate chronic pancreatitis, but is associated with high rates of failure to drain, secondary infection, and recurrence when pseudocysts that complicate acute necrotizing pancreatitis are approached. Laparoscopic pseudocyst gastrostomy or pseudocyst jejunostomy achieves adequate internal drainage, facilitates concomitant debridement of necrotic tissue within acute pseudocysts, and achieves good results with minimal morbidity. A randomized controlled trial that compares laparoscopic and endoscopic drainage techniques of retrogastric pseudocysts of chronic pancreatitis is required.     

Expression of vimentin and epithelial membrane antigen in human malignant lymphomas

Immunoreactivity with monoclonal antibodies against the intermediate filament protein, vimentin, and epithelial membrane antigen (EMA) was examined in 330 cases of lymphoma (317 non-Hodgkin's and 13 Hodgkin's lymphomas), 12 reactive lymph nodes and mononuclear cells of the peripheral blood using either indirect immunoperoxidase staining or the avidin-biotin immunoperoxidase complex technique. The cell origin of each tumor was established using a panel of monoclonal antibodies against lymphocyte differentiation antigens. There were 41 T-cell, 247 B-cell and 29 undetermined lymphomas, and 13 cases of Hodgkin's disease in the series. Vimentin was expressed in 24 T-cell lymphomas (58.5%) and 60 B-cell lymphomas (24.2%). This difference in frequency was statistically significant. Vimentin expression in follicular lymphomas was less frequent than in diffuse B-cell lymphomas. In diffuse lymphomas, small and medium cell types were more reactive with anti-vimentin than large cell types. Reed-Sternberg cells (R-S cells) in Hodgkin's disease were positive for vimentin in 11 cases (84.6%). The frequency of EMA reactivity in lymphomas was low, particularly in T-cell lymphomas. No positive cases were found among follicular lymphomas. In diffuse non-Hodgkin's lymphomas, EMA was expressed only in mixed and large cell types, but never in smaller ones. In conclusion, monoclonal antibodies against vimentin and EMA appear to be of limited usefulness for the diagnosis of non-Hodgkin's lymphomas, but anti-vimentin antibody may be used as an adjunct to the diagnosis of R-S cells in Hodgkin's disease.     

Experience-hormone interactions and maternal behavior in rats

Three studies were conducted to determine the effects of reproductive condition and hormonal background on the acquisition and retention of a prior maternal experience. In the first study five experience conditions were compared. All animals gave birth and received either no postpartum contact with pups or 1/2 hr, 1 hr, 2 hr or 24 hr of pup contact and were tested for maternal behavior 10 days later. Animals receiving pregnancy and parturitional experience, but minimal social experience with young, exhibited significantly longer maternal onset latencies than did groups receiving 2 or 24 hr of prior experience; also, comparisons of 10- and 30-day retention intervals indicated that animals tested 10 days after a 24-hr experience exhibited shorter latencies than those tested 30 days later. Thus, the duration of the postpartum experience and the interval since prior experience both affect the level of maternal responsiveness shown. In the second study six groups of females were tested. Four groups were permitted one day of interaction with pups either after parturition (primiparous animals) or following pup induction procedures (nulliparous animals) and were tested for their maternal responsiveness to foster pups 25-35 days later, either on day 19 of a subsequent pregnancy or following resumption of estrous cycling. For most measures of maternal behavior there were significant main experience and test effects; experienced and pregnant animals exhibited shorter latencies to retrieve, lick and crouch over pups than did inexperienced and cycling animals, respectively. Significant interactions were also found for genital licking latency as well as for retrieval and crouch frequencies.(ABSTRACT TRUNCATED AT 250 WORDS)     

Anaesthetic complications in plastic surgery

Anaesthesia related complications in plastic surgeries are fortunately rare, but potentially catastrophic. Maintaining patient safety in the operating room is a major concern of anaesthesiologists, surgeons, hospitals and surgical facilities. Circumventing preventable complications is essential and pressure to avoid these complications in cosmetic surgery is increasing. Key aspects of patient safety in the operating room are outlined, including patient positioning, airway management and issues related to some specific conditions, essential for minimizing post-operative morbidity. Risks associated with extremes of age in the plastic surgery population, may be minimised by a better understanding of the physiologic changes as well as the pre-operative and post-operative considerations in caring for this special group of patients. An understanding of the anaesthesiologist''s concerns during paediatric plastic surgical procedures can facilitate the coordination of efforts between the multiple services involved in the care of these children. Finally, the reader will have a better understanding of the perioperative care of unique populations including the morbidly obese and the elderly. Attention to detail in these aspects of patient safety can help avoid unnecessary complication and significantly improve the patients’ experience and surgical outcome.KEY WORDS: Anaesthesia, complications, plastic, surgery     

A functional genetic polymorphism on human carbonyl reductase 1 (CBR1 V88I) impacts on catalytic activity and NADPH binding affinity.

Human carbonyl reductase 1 (CBR1) metabolizes endogenous and xenobiotic substrates such as the fever mediator, prostaglandin E2 (PGE2), and the anticancer anthracycline drug, daunorubicin. We screened 33 CBR1 full-length cDNA samples from white and black liver donors and performed database analyses to identify genetic determinants of CBR1 activity. We pinpointed a single nucleotide polymorphism on CBR1 (CBR1 V88I) that encodes for a valine-to-isoleucine substitution for further characterization. We detected the CBR1 V88I polymorphism in DNA samples from individuals with African ancestry (p = 0.986, q = 0.014). Kinetic studies revealed that the CBR1 V88 and CBR1 I88 isoforms have different maximal velocities for daunorubicin (V(max) CBR1 V88, 181 +/- 13 versus V(max) CBR1 I88, 121 +/- 12 nmol/min . mg, p < 0.05) and PGE2 (V(max) CBR1 V88, 53 +/- 7 versus V(max) CBR1 I88, 35 +/- 4 nmol/min . mg, p < 0.01). Concomitantly, CBR1 V88 produced higher levels of the cardiotoxic metabolite daunorubicinol compared with CBR1 I88 (1.7-fold, p < 0.0001). Inhibition studies demonstrated that CBR1 V88 and CBR1 I88 are distinctively inhibited by the flavonoid, rutin (IC50 CBR1 V88, 54.0 +/- 0.4 microM versus IC50 CBR1 I88, 15.0 +/- 0.1 microM, p < 0.001). Furthermore, isothermal titration calorimetry analyses together with molecular modeling studies showed that CBR1 V88I results in CBR1 isoforms with different binding affinities for the cofactor NADPH (K(d) CBR1 V88, 6.3 +/- 0.6 microM versus K(d) CBR1 I88, 3.8 +/- 0.5 microM). These studies characterize the first functional genetic determinant of CBR1 activity toward relevant physiological and pharmacological substrates.     

A phase I pharmacokinetic and pharmacodynamic study of TKI258, an oral, multitargeted receptor tyrosine kinase inhibitor in patients with advanced solid tumors.

PURPOSE: To determine the maximum tolerated dose (MTD) dose-limiting toxicity, and pharmacokinetic and pharmacodynamic profile of TKI258 (formerly CHIR-258). EXPERIMENTAL DESIGN: A phase I dose escalating trial in patients with advanced solid tumors was performed. Treatment was initially as single daily doses on an intermittent 7-day on/7-day off schedule. Following a protocol amendment, a second schedule comprised, during cycle 1, 7-day on/7-day off treatment followed by 14 days of continuous daily dosing; subsequent cycles comprised 28 days of daily dosing. Pharmacokinetics and evaluation of phosphorylated extracellular signal-regulated kinase (ERK) in peripheral blood mononuclear cells were done during the first 28 days of each schedule. RESULTS: Thirty-five patients were treated in four intermittent (25-100 mg/d) and three continuous (100-175 mg/d) dosing cohorts. Observed drug-related toxicities were nausea and vomiting, fatigue, headache, anorexia, and diarrhea. Dose-limiting toxicities were grade 3 hypertension in one patient at 100 mg continuous dosing, grade 3 anorexia in a second patient at 175 mg, and grade 3 alkaline phosphatase elevation in a third patient at 175 mg. One patient had a partial response (melanoma) and two patients had stable disease >6 months. TKI258 pharmacokinetics were linear over the dose range of 25 to 175 mg. Five of 14 evaluable patients had modulation of phosphorylated ERK levels. CONCLUSIONS: The MTD was defined as 125 mg/d. Evidence of antitumor activity in melanoma and gastrointestinal stromal tumors warrants further investigation, and other phase I studies are ongoing. Further pharmacodynamic evaluation is required in these studies to evaluate the biological effects of TKI258.