Impact of stereotactic body radiation therapy on geriatric assessment and management for older patients with head and neck cancer using G8

PurposeManagement of head and neck cancers (HNC) in older adults is a common but challenging clinical scenario. We assess the impact of Stereotactic Body Radiation Therapy (SBRT) on survival utilizing the Geriatric-8 (G8) questionnaire.Materials and methods171 HNC patients, deemed medically unfit for definitive treatment, were treated with SBRT ± systemic therapy. G8 questionnaires were collected at baseline, at 4–6 weeks, and at 2–3 months post-treatment. Patients were stratified according to their baseline G8 score: <11 as ‘vulnerable’, 11–14 as ‘intermediate’, and >14 as ‘fit’. Overall survival (OS) was assessed through univariate Kaplan Meier analysis. Repeated measures ANOVA was used to determine if baseline characteristics affected G8 score changes.ResultsMedian follow-up was seventeen months. 60% of patients presented with recurrent HNC, 30% with untreated HNC primaries, and 10% with metastatic non-HNC primaries. Median age was 75 years. Median Charlson Comorbidity Index score was 2. 51% of patients were ‘vulnerable’, 37% were ‘intermediate’, and 12% were ‘fit' at baseline, with median survival of 13.2, 24.3, and 41.0 months, respectively (p = .004). Patients who saw a decrease in their follow-up G8 score (n = 69) had significantly lower survival than patients who had stable or increased follow-up G8 scores (n = 102), with median survival of 8.6 vs 36.0 months (p < .001).ConclusionThe G8 questionnaire may be a useful tool in upfront treatment decision-making to predict prognosis and prevent older patients from receiving inappropriate anti-cancer treatment. Decline in follow-up G8 scores may also predict worse survival and aid in goals of care following treatment.     

Pedophilia is linked to reduced activation in hypothalamus and lateral prefrontal cortex during visual erotic stimulation.

BACKGROUND: Although pedophilia is of high public concern, little is known about underlying neural mechanisms. Although pedophilic patients are sexually attracted to prepubescent children, they show no sexual interest toward adults. This study aimed to investigate the neural correlates of deficits of sexual and emotional arousal in pedophiles. METHODS: Thirteen pedophilic patients and 14 healthy control subjects were tested for differential neural activity during visual stimulation with emotional and erotic pictures with functional magnetic resonance imaging. RESULTS: Regions showing differential activations during the erotic condition comprised the hypothalamus, the periaqueductal gray, and dorsolateral prefrontal cortex, the latter correlating with a clinical measure. Alterations of emotional processing concerned the amygdala-hippocampus and dorsomedial prefrontal cortex. CONCLUSIONS: Hypothesized regions relevant for processing of erotic stimuli in healthy individuals showed reduced activations during visual erotic stimulation in pedophilic patients. This suggests an impaired recruitment of key structures that might contribute to an altered sexual interest of these patients toward adults.     

Effects of IFN-gamma and interleukin-1beta on major histocompatibility complex antigen and intercellular adhesion molecule-1 expression by 9L gliosarcoma: relevance to its cytolysis by alloreactive cytotoxic T lymphocytes.

To enhance the efficacy of cellular immunotherapy for gliomas, we tested the concept of using proinflammatory cytokine treatment with interferon-gamma (IFN-gamma) or interleukin-1beta (IL-1beta) or both to render glioma cells more susceptible to cytolysis by alloreactive cytotoxic T lymphocytes (aCTL). The cytokines, separately or in combination, were able to upregulate major histocompatibility complex (MHC) class I antigen or intercellular adhesion molecule-1 (ICAM-1) on Fischer rat 9L gliosarcoma cells. 9L cells were incubated in vitro for 24, 48, or 72 h with varying concentrations of rat IFN-gamma (0-2000 U/ml) or recombinant human IL-1 (rHUIL-1) (0-1000 U/ml) or both. By 48 h, IFN-gamma (500 U/ml) maximally induced the percentage of positive expressing cells and the relative antigen density of MHC class I and ICAM-1 on 9L cells, whereas IL-1 induced only ICAM-1 expression. Simultaneous incubation of IL-1 with IFN-gamma did not further affect the induction of class I on 9L cells more than that achieved with IFN-gamma alone. 9L cells with upregulated MHC class I and ICAM-1 expression were more sensitive to lysis by aCTL in in vitro cytotoxicity assays, regardless of whether the precursor aCTL came from naive or from 9L-immunized rats. Furthermore, inhibition of 9L cytotoxicity in assays that included blocking antibodies to MHC class I or to ICAM-1 revealed that T cell receptor (TCR) interactions with MHC class I and that ICAM-1 interactions with lymphocyte function-associated-1 (LFA-1) antigen account for a portion of the glioma lysis by aCTL.     

Neuroleptic malignant syndrome and serotonin syndrome in the critical care setting: case analysis.

BACKGROUND: Serotonin syndrome (SS) and neuroleptic malignant syndrome (NMS) are medical emergencies associated with psychotropic administration. Differentiation and treatment can be complex, especially when features of both syndromes are present and the patient has taken both serotonergic and neuroleptic agents. METHOD: Case analysis of a poly-drug overdose (venlafaxine, topiramate, divalproex sodium, risperidone, and carbamazepine) presenting with mixed SS/NMS features and whose clinical management suggests a practical algorithm for treatment of undifferentiated SS/NMS in critical care settings. RESULTS: The suggested algorithm includes: 1) Supportive care and withdrawal of all potentially offending agents; 2) Laboratory evaluation with prompt initiation of treatment for both disorders--cyproheptadine for SS and dantrolene for NMS; 3) Do not use bromocriptine (contraindicated in SS) or chlorpromazine (contraindicated in NMS) initially; 4) Add bromocriptine when clinical presentation becomes consistent with NMS (SS can be prolonged if serotonergic agent has long half-life). CONCLUSIONS: Prompt and appropriate identification and intervention are essential for successful management of SS and NMS. The suggested treatment algorithm allows for specific treatment of both disorders and avoids potentially exacerbating either one. The algorithm derived from this case could serve as both a practical guideline and impetus for further investigation in light of increasing psychotropic co-administration.     

Influence of small additions of hexamethylphosphoric triamide on the kinetics of polymerization of styrene in THF

Unsaturated polyamides from methyl-fumaric (2-methyl-fumaric and 2.3-dimethyl-fumaric) acid dichlorides and diamines, i.e. 1.6-hexamethylenediamine, 1.10-decamethylenediamine, m-xylylenediamine, piperazine and trans-2.5-dimethylpiperazine were synthesized by low-temperature polycondensation. The polymer structures and properties were investigated by IR, X-ray, NMR, DSC, and TGA analyses. All polyamides were found to be soluble in several volatile organic solvents: furthermore – unlike polyamides derived from unsubstituted fumaric acid – polyamides from substituted fumaric acid derived from primary diamines showed melting or softening points.     

Transvaginal sonography and rectal endoscopic sonography for the assessment of pelvic endometriosis: a preliminary comparison

BACKGROUND: Endometriosis and possible rectal involvement are difficult to assess by physical examination. Previous studies have shown the diagnostic value of magnetic resonance imaging and rectal endoscopic sonography (RES) in this setting, but not that of transvaginal sonography (TVS). The aims of this study were to compare the accuracy of TVS and RES for the diagnosis of pelvic endometriosis, and to compare the results with histological findings. PATIENTS AND METHODS: In a prospective study, 30 consecutive patients referred with clinical signs of endometriosis underwent TVS and RES; the images were interpreted blindly with regard to physical findings. RESULTS: Endometriosis was confirmed histologically in 28 (93%) of the 30 patients. Endometriomas were also present in 67% of cases. For the diagnosis of uterosacral endometriosis, the sensitivity, specificity, and positive and negative predictive values of TVS and RES were 75 and 75%, 83 and 67, 95 and 90%, and 45 and 40% respectively. For the diagnosis of rectosigmoid endometriosis, the sensitivity, specificity, and positive and negative predictive values of TVS and RES were 95 and 82%, 100 and 88%, 100 and 95%, and 89 and 64% respectively. CONCLUSION: Despite the large proportion of our patients who had intestinal endometriosis, representing a possible source of bias, our results suggest that TVS is as efficient as RES for detecting posterior pelvic endometriosis and should therefore be used as the first-line examination.     

ABCA1 gene deletion protects against cerebral malaria: potential pathogenic role of microparticles in neuropathology

The ATP-binding cassette transporter A1 (ABCA1) modulates the transbilayer distribution of phosphatidylserine at the outer leaflet of the plasma membrane. This external exposure of phosphatidylserine is a hallmark of microparticle production and is impaired in ABCA1(-/-) mice. In this study, we report about the complete resistance to cerebral malaria of these mice. On analysis of histological and systemic parameters we evidenced an impairment of cellular responses to Plasmodium berghei ANKA infection in ABCA1(-/-) mice, as shown by lower plasma tumor necrosis factor levels, a weaker up-regulation of endothelial adhesion molecules in brain microvessels, a reduced leukocyte sequestration, as well as an ablated platelet accumulation. Besides, the number and the procoagulant activity of microparticles were dramatically reduced in the plasma of ABCA1(-/-) compared to ABCA1(+/+) mice. Moreover, microparticles derived from Plasmodium berghei ANKA-infected ABCA1(+/+) mice induced a significant increase of tumor necrosis factor release by noninfected macrophages. In ABCA1(-/-) mice platelet and macrophage responses to vesiculation agonists were ablated and reduced, respectively. Altogether, by pointing out the ABCA1 transporter as a major element controlling cerebral malaria susceptibility, these data provide a novel insight into its pathophysiological mechanisms and are consistent with a pathogenic role of microparticles in this neurological syndrome.     

Eutopic endometrium and peritoneal,ovarian and bowel endometriotic tissues express a different profile of matrix metalloproteinases-2, -3 and -11, and of tissue inhibitor metalloproteinases-1 and -2

Endometriosis is subsequent to the ability of endometrial glands to invade normal tissues. Matrix metalloproteinases (MMPs)—enzymes that mediate normal tissue turnover, including endometrial breakdown during menstruation—appear to be involved in this invasive process. Here, we examined the immunohistochemical expression of MMP-2, MMP-3, MMP-11, tissue inhibitor metalloproteinase (TIMP)-1 and TIMP-2 in endometrium from women with (n=9) or without endometriosis (n=18) in comparison with peritoneal (n=20), ovarian (n=20) and colorectal endometriosis (n=20). Women with endometriosis showed decreased endometrial MMP-2 expression compared with women without endometriosis (mean±SD positive cells: 24.3±28.3% and 69.3±12.1%), together with loss of MMP-3 expression (0 versus 17.5%±20.2). MMP-11, TIMP-1 and TIMP-2 expression was similar in the two groups. Endometrial MMP-2, -3 and -11 expression and TIMP-1 and -2 expression were similar in women with endometriosis and in those with peritoneal endometriosis. MMP-2, -3 and -11 expression was higher in colorectal endometriosis than in ovarian and peritoneal endometriosis. TIMP-2 expression was lower in colorectal endometriosis (P=0.0002) and ovarian endometriotic cysts (P=0.003) than in peritoneal endometriosis. TIMP-1 expression did not vary according to the location of endometriotic lesions. These results suggest that MMP-2 and -3 and TIMP-2 may be involved in the pathogenesis of endometriosis. Interestingly, MMP-2 and -3 overexpression was related to the infiltrative nature of endometriotic lesions, with possible sequential expression from peritoneal to colorectal endometriosis.     

Effect of Pyrimidine Nucleosides on Body Temperatures of Man and Rabbit in Relation to Pharmacokinetic Data

The effect of high-dose uridine on body temperatures of rabbits and man has been studied in relation to plasma concentrations of uridine and its catabolite uracil. Uridine induced fever in both rabbits and man. High-dose cytidine had no influence on body temperature in rabbits. Plasma concentrations of uridine were between 1 and 1.5 mM at 30 min after an iv bolus injection of 400 mg uridine/kg in rabbits and reached peak levels of 2 mM after a 1-hr infusion of 12 g uridine/m² in man. The plasma concentration of cytidine in rabbits was about 0.5 mM and that of uridine was 0.30 mM at 30 min after an iv bolus injection of 400 mg cytidine/kg. The mean residence time for uridine in patients and rabbits varied between 80 and 195 min. The area under the plasma concentration–time curve (AUC) for uridine in rabbits was 2.0 mmol · hr/liter, and that for cytidine was 0.6 mmol · hr/liter. A large AUC for uridine indicates a prolonged exposure of tissues to uridine, which might lead to extensive formation of degradation products. The administration of some of these catabolites, dihydrouracil (at 20–40 mg/kg), carbamyl--alanine (at 60 mg/kg), and -alanine (at 300–400 mg/kg), resulted in a significant increase in body temperature. It is concluded that the change in body temperature associated with uridine administration was not due to bacterial pyrogens but that one of the degradation products might be involved in thermoregulation.