166Ho-DOTMP radiation-absorbed dose estimation for skeletal targeted radiotherapy.

166Ho-1,4,7,10-tetraazacyclododecane-1,4,7,10-tetramethylene-phosphonate (DOTMP) is a tetraphosphonate molecule radiolabeled with 166Ho that localizes to bone surfaces. This study evaluated pharmacokinetics and radiation-absorbed dose to all organs from this beta-emitting radiopharmaceutical. METHODS: After two 1.1-GBq administrations of 166Ho-DOTMP, data from whole-body counting using a gamma-camera or uptake probe were assessed for reproducibility of whole-body retention in 12 patients with multiple myeloma. The radiation-absorbed dose to normal organs was estimated using MIRD methodology, applying residence times and S values for 166Ho. Marrow dose was estimated from measured activity retained after 18 h. The activity to deliver a therapeutic dose of 25 Gy to the marrow was determined. Methods based on region-of-interest (ROI) and whole-body clearance were evaluated to estimate kidney activity, because the radiotracer is rapidly excreted in the urine. The dose to the surface of the bladder wall was estimated using a dynamic bladder model. RESULTS: In clinical practice, gamma-camera methods were more reliable than uptake probe-based methods for whole-body counting. The intrapatient variability of dose calculations was less than 10% between the 2 tracer studies. Skeletal uptake of 166Ho-DOTMP varied from 19% to 39% (mean, 28%). The activity of 166Ho prescribed for therapy ranged from 38 to 67 GBq (1,030-1,810 mCi). After high-dose therapy, the estimates of absorbed dose to the kidney varied from 1.6 to 4 Gy using the whole-body clearance-based method and from 8.3 to 17.3 Gy using the ROI-based method. Bladder dose ranged from 10 to 20 Gy, bone surface dose ranged from 39 to 57 Gy, and doses to other organs were less than 2 Gy for all patients. Repetitive administration had no impact on tracer biodistribution, pharmacokinetics, or organ dose. CONCLUSION: Pharmacokinetics analysis validated gamma-camera whole-body counting of 166Ho as an appropriate approach to assess clearance and to estimate radiation-absorbed dose to normal organs except the kidneys. Quantitative gamma-camera imaging is difficult and requires scatter subtraction because of the multiple energy emissions of 166Ho. Kidney dose estimates were approximately 5-fold higher when the ROI-based method was used rather than the clearance-based model, and neither appeared reliable. In future clinical trials with 166Ho-DOTMP, we recommend that dose estimation based on the methods described here be used for all organs except the kidneys. Assumptions for the kidney dose require further evaluation.     

Heart Rate Variability Predicts Severe Hypotension after Spinal Anesthesia

Background: Hypotension due to vasodilatation after spinal anesthesia (SA) may be harmful. Heart rate variability, an indirect measure of autonomic control, may predict hypotension.

Methods: One hundred patients were studied. Retrospectively, heart rate variability was analyzed in 30 patients, classified depending on the lowest systolic blood pressure (SBP) after SA. Seventy patients were studied prospectively, assigned to one of two groups by their low to high frequency ratio (LF/HF) before SA. Sensitivity and specificity of LF/HF for prediction of decrease of SBP greater 20% of baseline were tested.

Results: Retrospective analysis showed differences of LF/HF depending on the degree of hypotension after SA. Prospective analysis demonstrated significant differences of SBP after SA depending on baseline LF/HF (mean +/- SD): low LF/HF (1.3 +/- 0.7) = > SBP: 91 +/- 8% of baseline versus high LF/HF (5.5 +/- 2.4) = > SBP: 66 +/- 10% of baseline (P < 0.05). Baseline LF/HF as well as high frequency and proportional decrease of SBP after SA correlated significantly, in contrast to baseline hemodynamic parameters heart rate and SBP. A receiver operator curve characteristic analysis showed a sensitivity and specificity of LF/HF > 2.5 of 85% to predict SBP decrease of greater than 20% of baseline after SA.     

Use of an in vitro model of tissue-engineered human skin to study keratinocyte attachment and migration in the process of reepithelialization

To produce a stable epidermis, keratinocytes need to be firmly attached to the basement membrane. However, following wounding, keratinocytes are required to develop a migratory phenotype in order to reepithelialize the wound. To investigate some of the issues underlying reepithelialization, we have developed a three-dimensional in vitro model of tissue-engineered skin, comprising sterilized human dermis seeded with human keratinocytes and dermal fibroblasts. Using this model, we have shown that the inclusion of fibroblasts within the model increases the stability of keratinocyte attachment. We have also demonstrated that keratinocyte migration occurs most effectively in the absence of a basement membrane and following the inclusion of fibroblasts in the model. In addition, subjecting the keratinocyte layer to mechanical trauma induces a migratory phenotype. We conclude that this three-dimensional in vitro wound model can be used to increase our understanding of the factors that enhance keratinocyte migration and hence wound healing in vivo.     

Effect of catalase supplementation in storage media for avulsed teeth

Abstract – The type of liquid medium used to store avulsed teeth prior to replantation has been shown to affect the long‐term prognosis. One possibility is that some storage media contain hydrogen peroxide (H₂O₂) that may be toxic to periodontal ligament cells. Therefore, the aim of this study was to determine if the addition of catalase to storage media improved the prognosis of replanted dog teeth. Forty‐eight mongrel premolar roots were endodontically treated, extracted, randomly divided and placed into one of four storage media: Hank's balanced salt solution (HBSS), containing no antioxidant); Viaspan, containing the antioxidant, glutathione, or the same two media supplemented with catalase(100 U ml^?1) for 1, 5, or 26 h prior to replantation. After 2 months, the dogs were euthanized and the roots histologically examined to evaluate the attachment tissues. Regardless of the storage medium used, overall healing was excellent and only 4% of the roots displayed inflammatory or replacement resorption. When roots from the different storage media were compared, those stored in HBSS were found to display the highest incidence of surface resorption (55.7%). Supplementation of HBSS with catalase resulted in a lower level of surface resorption (48.6%) that was statistically significant (P < 0.05). Roots stored in Viaspan – or + catalase displayed even lower levels of surface resorption (41.3 and 38.2%, respectively). The improvement observed with catalase‐supplemented HBSS was confined to the 45‐min incubation period; only Viaspan – or + catalase reduced surface resorption at the 5‐ and 26‐h incubations. Collectively, these data demonstrate that roots stored in media containing antioxidant activity undergo less surface resorption. These results suggest that low levels of H₂O₂ in storage media for avulsed teeth may adversely affect periodontal ligament cells.     

Low level of response to alcohol as associated with serotonin transporter genotype and high alcohol intake in adolescents.

BACKGROUND: A low level of response to alcohol has been associated with both the genetic constitution of the regulatory region (SLC6A4) of the human serotonin (5-hydroxytryptamine, 5-HT) transporter (5-HTT) and with future alcohol intake and an increased risk for alcoholism. To date, all studies of relevant polymorphisms have been carried out in populations in the United States. METHODS: Data were extracted from a subset (n = 243) of a cohort of children who have been observed since birth through evaluation of the family history of alcoholism and psychosocial risk influences. At age 16 years, the response to alcohol was assessed with the Self-Rating of the Effects of Alcohol (SRE) questionnaire, and the average amount of alcohol intake per month was assessed during the prior 6 months. Additional variables that were measured included the 5-HTT genotype, externalizing behavior, and sociodemographic variables, such as gender and age. RESULTS: The level of response to alcohol was significantly lower among carriers of two long alleles of the 5-HTT regulatory region compared with carriers of one or two short alleles (Mann-Whitney U = 5225.0, p = .005). In a multiple regression analysis, the level of response to alcohol and externalizing behavior but not psychosocial factors significantly predicted the average amount of alcohol intake per month. CONCLUSIONS: This study demonstrates that, independent of the assessed psychosocial variables, the 5-HTT genotype correlated with the level of response to alcohol and predicted alcohol intake among 16-year-old adolescents.     

Episodic memory bias and the symptoms of schizophrenia.

Much of the research on episodic memory in schizophrenia spectrum disorders has focused on memory deficits and how they relate to clinical measures such as outcome. Memory bias refers to the modulatory influence that state or trait psychopathology may exert on memory performance for specific categories of stimuli, often emotional in nature. For example, subjects suffering from depression frequently have better memory for negative stimuli than for neutral or positive ones. This dimension of memory function has received only scant attention in schizophrenia research but could provide fresh new insights into the relation between symptoms and neurocognition. This paper reviews the studies that have explored memory biases in individuals with schizophrenia. With respect to positive symptoms, we examine studies that have explored the link between persecutory delusions and memory bias for threatening information and between psychosis and a memory bias toward external source memory. Although relatively few studies have examined negative symptoms, we also review preliminary evidence indicating that flat affect and anhedonia may lead to some specific emotional memory biases. Finally, we present recent findings from our group delineating the relation between emotional valence for faces and memory bias toward novelty and familiarity, both in schizophrenia patients and in healthy control subjects. A better understanding of the biasing effects of psychopathology on memory in schizophrenia (but also on other cognitive functions, such as attention, attribution, and so forth) may provide a stronger association between positive and negative symptoms and memory function. Memory measures sensitive to such biases may turn out to be stronger predictors of clinical and functional outcome.     

宫腹腔镜联合手术诊治不孕症150例分析

目的:探讨宫腹腔镜联合手术在诊治不孕症中的应用。方法:对150例不孕症患者行宫腹腔镜联合手术,对不孕症病因进行诊断,同时行治疗。结果:盆腔粘连和输卵管阻塞是不孕症的主要原因。子宫内膜息肉和正常盆腔占次要比例。子宫内膜异位症和多囊卵巢也是主要病因。150例同时行宫腹腔镜输卵管通液和各种疾病的治疗。联合手术后妊娠率为48.8%。结论:腹腔镜联合手术,在一次麻醉下,可以对不孕的原因全面评价和明确诊断,在诊断同时进行治疗,对不孕症的诊断和治疗有重大的意义,值得推广。     

DMPP-evoked increases in postganglionic sympathetic nerve activity and blood pressure occurs by two mechanisms in the rat

1 Intravenous administration of the ganglionic nicotinic receptor agonist DMPP (1,1-dimethyl-4-phenylpiperazinium iodide) into urethane-anaesthetized rats evoked dose-dependent increases in mean arterial pressure (MAP) and renal sympathetic nerve activity (RSNA). 2 The ganglionic nicotinic receptor antagonists pentolinium and hexamethonium either alone or combined did not inhibit the increase in RSNA and MAP evoked by 50 to 200 μg kg^?1 doses of DMPP. The increase in renal sympathetic nerve activity evoked by DMPP occurred as a brief burst in firing. 3 The increase in MAP, but not RSNA, evoked by DMPP in the presence of pentolinium was inhibited by the selective α₁-adrenergic receptor antagonist prazosin. 4 The non-selective α-adrenoceptor and NPY receptor antagonist benextramine also inhibited the increase in MAP without inhibiting the increase in RSNA. Surprisingly, the combination of benextramine and pentolinium, or benextramine and hexamethonium, completely blocked the DMPP-evoked increase in RSNA and thus the increase in MAP. 5 The uptake₁ antagonist desipramine combined with pentolinium did not affect the DMPP-evoked increases in MAP or RSNA when compared to the responses evoked in the presence of pentolinium alone. 6 Adding the selective M₁ muscarinic receptor antagonist telenzepine to pentolinium and prazosin did not inhibit the increase in RSNA evoked by a 100 μg kg^?1 dose of DMPP. 7 While the DMPP-evoked increase in MAP in the presence of ganglionic nicotinic receptor antagonists is primarily dependent upon activation of α₁-adrenoceptors, the increase in RSNA occurs via activation of ganglionic nicotinic receptors and activation of a mechanism susceptible to blockade by benextramine.     

Pressor response to posterior hypothalamic administration of carbachol is mediated by muscarinic M3 receptor.

Unilateral microinjection of the acetylcholine receptor agonist carbachol into the posterior hypothalamic nucleus evokes a pressor response in the conscious, freely moving rat. To further localize this response 3.3 or 5.5 nmol of carbachol was microinjected in a volume of 50 nl directly into and outside the region of the posterior hypothalamic nucleus. Administration of carbachol outside the posterior hypothalamic nucleus failed to evoke a change in blood pressure indicating that the carbachol-induced pressor response is mediated from the posterior hypothalamic nucleus. Since posterior hypothalamic administration of atropine completely blocks the carbachol-induced increase in blood pressure and atropine blocks the three pharmacologically identified muscarinic receptor subtypes, methylatropine and progressively more selective muscarinic antagonists were administered into the posterior hypothalamic nucleus prior to 5.5 nmol of carbachol. Microinjection of the M1/M2/M3 muscarinic antagonist methylatropine (0.19-12.5 nmol), the M1/M3 antagonist 4-DAMP (4-diphenylacetoxy-N-methylpiperidine; 0.9-3.6 nmol), the M1 antagonist pirenzepine (9.5-38 nmol), the M2 antagonist methoctramine (5.5-44 nmol), or the M3 antagonist p-F-HHSiD (para-fluoro-hexahydro-sila-difenidol; 2.1-8.3 nmol) inhibited the peak increase in mean arterial pressure and the area under the curve of the change in mean arterial pressure versus time plot in a dose-dependent manner. Log ID50s calculated for the antagonists from the dose-response curves were found to correlate significantly with the log Kis of the antagonists for the muscarinic M3 receptor subtype. These results demonstrate that the increase in mean arterial pressure evoked by microinjection of carbachol into the posterior hypothalamic nucleus is mediated by the muscarinic M3 receptor.