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71.
Chronic childhood neuropathies are predominantly hereditary in origin. Specific distinct clinical entities have been described, however, occasionally children with an unusual clinical phenotype are encountered in practice. We describe four children (3 males, 1 female) of Lebanese Moslem descent all sharing a common great-great-grandparent pairing with such a novel clinical spectrum. The three males were first cousins, each the product of a different parental consanguineous (i.e., parents second cousins) mating, whereas the female was a third cousin to each of the males whose parents were also second cousins. Each child presented early in life with developmental delay with associated hypotonia and areflexia. All had a sensorineural hearing loss documented and two of the patients were dysmorphic in facial appearance. Nerve conduction studies highlighted a sensory axonal neuropathy and sural nerve biopsy undertaken in two patients confirmed an axonal neuropathy. Detailed genetic and metabolic testing was negative. Followed into later childhood, each child continued to manifest motoric impairment, unsteadiness, areflexia, and cognitive disability. These children appear to provide evidence for a novel autosomal recessive inherited chronic predominantly sensory neuropathy that shares core clinical features with observed variability in associated symptoms. 相似文献
72.
In completed and ongoing clinical trials, adenovirus-mediated (Ad.) expression of herpes-simplex-virus thymidine-kinase (HSV-tk)
gene transduction followed by ganciclovir (GCV) therapy has produced limited toxicity and evidence of antitumor activity following
injection of the prostate. Furthermore, this system has been shown to direct systemic antitumor activity in several experimental
cancer models, including that of prostate cancer, which may serve as the basis for in-situ immunomodulatory gene therapy.
In a mouse model of prostate cancer, natural killer (NK) cells have been identified as the mediator of antimetastatic activity
following Ad.HSV-tk + GCV, resulting in the combination of Ad.HSV-tk and adenovirus-mediated expression of interleukin 12
(Ad.IL-12) to exploit this cytokine's ability to enhance NK proliferation and cytotoxicity. Combination therapy demonstrated
superior local and systemic growth suppression over that obtained with either therapy alone. Importantly, when the metastatic
tumor burden was increased to an extent that negated the growth-suppressive activity directed by Ad.HSV-tk + GCV or Ad.IL-12
alone, combination therapy continued to demonstrate significant growth suppression. Examination of tumor-infiltrating lymphocytes
documented enhanced NK lytic activity following combination therapy. Therefore, it appears that the combination of Ad.HSV-tk
and Ad.IL-12 should be validated in a clinical trial for the treatment of prostate cancer. 相似文献
73.
74.
75.
Touijer K Kuroiwa K Saranchuk JW Hassen WA Trabulsi EJ Reuter VE Guillonneau B 《The Journal of urology》2005,173(3):765-768
PURPOSE: We correlated intraoperative video documentation and pathology findings to understand the mechanisms by which positive surgical margins occur and improve the surgical technique. MATERIALS AND METHODS: Between January 2003 and May 2004, 240 consecutive patients underwent laparoscopic radical prostatectomy, of whom 180 had pT2 prostate cancer and represent the population of this study. After the first 90 patients (group 1) we started a quality assurance study, analyzing intraoperative video recordings and correlating them with pathology findings in patients with a positive margin. The cancer characteristics and positive margin rate were compared between the first 90 patients and the subsequent 90 after the study was initiated (group 2). RESULTS: Of the 12 cases of positive surgical margins studied the video review helped identify 8 with a technical error. In all 4 cases in which a technical error could not be identified the positive margin site was at the distal apex. The most frequent identifiable mechanism by which positive margins occurred was a capsular tear during neurovascular bundle dissection. The 2 groups were comparable in regard to preoperative cancer characteristics and total tumor volume. In patients who underwent bilateral nerve sparing the positive margin rate was 10.6% in group 1 and 5.4% in group 2 (p = 0.18). All positive margins in group 2 involved the prostatic apex. CONCLUSIONS: Quality assurance efforts through pathological and intraoperative documentation review can help decrease the positive margin rate, particularly in organ confined disease. However, eradicating positive margins at the distal prostatic apex remains a challenge. 相似文献
76.
Colorectal foreign bodies (FBs) may be ingested or introduced transanally and then migrate proximally. Without a reliable history, it may be impossible to determine which way a certain colorectal FB gained access. We present a case of a nonverbal mentally retarded boy with a flat piece of plastic impacted in the sigmoid colon, the colonoscopic extraction of which failed. He underwent laparotomy more than a year later to remove the FB, where chronic perforation of the sigmoid colon was discovered. The perforation was sealed with extensive adhesions to the pelvic wall, and histologically, the colon showed a chronic granulomatous reaction. We discuss the types, presentations, and diagnosis of intestinal perforation with FBs. Chronic perforation may present with radiologic and pathologic features that suggest inflammatory bowel disease. 相似文献
77.
An 8-week open-label trial of a 6-day course of mifepristone for the treatment of psychotic depression 总被引:6,自引:0,他引:6
Simpson GM El Sheshai A Loza N Kingsbury SJ Fayek M Rady A Fawzy W 《The Journal of clinical psychiatry》2005,66(5):598-602
OBJECTIVE: Several investigations suggest that mifepristone leads to the rapid amelioration of psychotic depression. However, these studies were of short duration (1 week or less) and included subjects who were taking other psychotropic medications. The goals of this study were to extend these findings by conducting an 8-week trial of mifepristone for subjects with psychotic depression who were taking no concomitant psychiatric medications. METHOD: Twenty subjects with a DSM-IV major depressive episode with psychotic features (for convenience we use the term psychotic depression) taking no psychotropic medications were given a 6-day course of mifepristone and followed as inpatients for a total of 8 weeks. Nonblinded ratings using the Hamilton Rating Scale for Depression (HAM-D) and Clinical Global Impressions scale (CGI) were performed at baseline and at the end of weeks 1, 4, and 8. The Brief Psychiatric Rating Scale (BPRS) was also administered at baseline and after weeks 4 and 8. Subjects were recruited between February 2003 and December 2003. RESULTS: Significant improvements in HAM-D and CGI scores were shown after 1 week and between weeks 1 and 4 but not between weeks 4 and 8. BPRS scores improved significantly after week 4, while the improvement in BPRS scores between weeks 4 and 8 was of borderline significance. CONCLUSION: Mifepristone appears to be a useful intervention for psychotic depression, leading to significant improvements even after a 1-week course of administration. Issues related to its optimal dosing and to prediction of response are discussed, as are the implications of lack of a placebo group and the use of nonblinded ratings in the present study. 相似文献
78.
Shehabi AA Abu-Al-Soud W Mahafzah A Khuri-Bulos N Abu Khader I Ouis IS Wadström T 《Scandinavian journal of infectious diseases》2004,36(3):174-178
Over a 1-y period, 26 inpatients at the Jordan University Hospital in Amman were detected with bacteraemia (23 cases) or respiratory tract colonized with B. cepacia (3 cases). A combination of genetic identification and molecular typing has proved that all cases were caused by a single epidemic strain of B. cepacia genomovar IIIa. Nosocomial infections could be documented in 21/26 (81%) patients, mostly with severe underlying or malignant diseases other than cystic fibrosis, but the source of infection was undetected. The overall mortality related to infection with B. cepacia was 42%. All B. cepacia isolates were resistant to ampicillin, amikacin, carbenicillin and gentamicin; and mostly susceptible to piperacillin, chloramphenicol, cotri-moxazole, tetracycline, ceftazidime, and tazocin (62-88%). This study demonstrates the nosocomial and high fatality of B. cepacia genomovar IIIa in Jordanian patients suffering from diseases other than cystic fibrosis. 相似文献
79.
Ajaj W Lauenstein TC Pelster G Goehde SC Debatin JF Ruehm SG 《Journal of magnetic resonance imaging : JMRI》2004,19(2):216-221
PURPOSE: To prove the feasibility of air-distended magnetic resonance colonography (MRC) and compare it with water-based distention. MATERIALS AND METHODS: In five volunteers, the colon was imaged twice: once after distending the colon with air and a second time after distending the colon with water. A total of 50 patients, who had been referred to colonoscopy for a suspected colorectal pathology were randomized into water-distention (N = 25) and air-distention (N = 25) groups. A contrast-enhanced T1-weighted three-dimensional volume interpolated breath-hold (VIBE) sequence was collected. Comparative analysis was based on qualitative ratings of image quality and bowel distention, as well as contrast-to-noise ratio (CNR) measurements for the colonic wall with respect to the colonic lumen. In addition, patient acceptance was evaluated. RESULTS: Inflammatory changes and colorectal masses were correctly identified on MRC in eight patients each. One 4-mm polyp identified at colonoscopy was missed on water-distended MRC. There were no false positive findings. No significant differences were found between air- and water-distention regarding discomfort levels and image quality. The presence of air in the colonic lumen was not associated with susceptibility artifacts. CNR of the contrast-enhanced colonic wall, as well as bowel distention, were superior on air-distended three-dimensional data sets. CONCLUSION: MRC can be performed using either water or air for colonic distention. Both techniques permit assessment of the colonic wall and identification of colorectal masses. While discomfort levels are similar for both agents, MRC with air provides higher CNR and better colonic distention. 相似文献
80.
Shalaby WS Yeh H Woo E Corbett JT Gray H June CH Shalaby SW 《Journal of biomedical materials research. Part B, Applied biomaterials》2004,69(2):173-182
An absorbable microparticulate cation exchanger was synthesized as a versatile carrier for biologically active proteins. In this work, acid-terminated polyglycolide (or polyglycolic acid) microparticulates (PG-MP) were surface modified for either sustained release of cytokines or as a platform for immunomodulation. The intended goal was to achieve in situ recruitment/maturation of dendritic cells and activation of T cells for tumor immunotherapy. PG-MP were prepared with a volume weighted mean diameter of 7.02 micro (range: 2.09-14.58 micro). Accessible carboxylic acid groups were determined to be 0.3 mmol/g with a corresponding zeta potential of -21.87 mV in phosphate-buffered saline. Under low magnification, scanning electron microscopy (SEM) revealed a highly textured surface due to processing from repetitive jet milling. However, a moderately porous architecture was noted at higher magnification. Electron spectroscopy for chemical analysis was used to characterize the PG-MP surface before and after adsorption of human granulocyte-macrophage colony stimulating factor (GM-CSF). Adsorption of GM-CSF on PG-MP (PG-GMCSF) resulted in a modest increase in the surface atomic concentration of nitrogen (0.97%). Pretreating the surface with poly-L-lysine (PG/Lys-GMCSF) prior to adding GM-CSF produced a nearly threefold increase in the surface nitrogen concentration (4.20% compared to 1.47%). This manipulation not only increased loading content, but also prolonged the release of GM-CSF released from 6 days to 26 days. ESCA on the post-release PG-MP samples (PG-GMCSF and PG/Lys-GMCSF) revealed a similar residual surface nitrogen concentration (2.26% vs. 2.35%). The observation was consistent with irreversibly adsorbed GM-CSF. It is postulated that irreversibly bound GM-CSF is released over time as a function of microparticulate degradation. Biological activity of released GM-CSF was confirmed by the proliferation of a GM-CSF-dependent cell line (TF-1) in the presence of microparticulates. PG-MP mediated activation of T cells was achieved through irreversible adsorption of either antimouse cd3 plus antimouse cd28 monoclonal antibodies (alpha-cd3/cd28-MP) or antihuman CD3 plus antihuman CD28 monoclonal antibodies (alpha-CD3/CD28-MP) on PG-MP. Irreversibly adsorbed antibodies were capable of activating both resting mouse and human T cells. Intracellular flow cytometry on mouse T cells revealed that nearly 50% of the activated cells produced interferon-gamma (IFN-gamma). This was consistent with a TH-1 or cell-mediated response. In vivo efficacy was evaluated in a mouse flank tumor model showing a significant antitumor effect both alone and in combination. Combination therapy was most effective at preventing tumor implantation (8/8 mice) and was able induce tumor regression (4/7 mice) and/or stable disease (3/7 mice) in a regression model. In these studies, immunohistochemistry was used to confirm local recruitment of dendritic cells. In conclusion, the PG-MP represents a novel absorbable cation exchanger that can be readily manipulated to deliver biologically active proteins for immunotherapy. 相似文献