A Novel Nomogram to Identify Candidates for Extended Pelvic Lymph Node Dissection Among Patients with Clinically Localized Prostate Cancer Diagnosed with Magnetic Resonance Imaging-targeted and Systematic Biopsies

Background

Available models for predicting lymph node invasion (LNI) in prostate cancer (PCa) patients undergoing radical prostatectomy (RP) might not be applicable to men diagnosed via magnetic resonance imaging (MRI)-targeted biopsies.

Proximal load transfer with a stemless uncemented femoral implant

Bone stock preservation is crucial when performing total hip replacement in young patients. The aim is to save good bone stock for a possible revision procedure. Furthermore, there is an increasing demand from young and active patients to receive a new joint which allows a normal or nearly normal life style. With this in mind, we began, in 1993, to develop a new femoral implant. The purpose of this ultra-short stem was a physiologic strain distribution on the proximal femur with a proximal load transfer from the implant to the femoral bone. Main features were an almost complete absence of the diaphyseal portion of the stem, a well defined lateral flare with load transfer on the lateral column of the femur, and a very high femoral neck cut. These innovations resulted in a conservative implant on both the bone stock and the soft tissues. This implant, in the first years, was recommended only for young and active patients. Over the last thirteen years, this project has undergone several modifications but the basic principles of the implant have remained the same. In the present review, we present the rationale, the surgical technique and the clinical and experimental results so far obtained with this implant.     

Epilepsy syndromes associated with hypothalamic hamartomas.

PURPOSE: Hypothalamic hamartoma (HH) related epilepsy presents with gelastic seizures (GS), other seizure types and cognitive deterioration. Although seizure origin in GS has been well established, non-GS are poorly characterized. Their relationship with the HH and cognitive deterioration remains poorly understood. We analyzed seizure type, spread pattern in non-GS and their relationship with the epileptic syndrome in HH. METHODS: We documented all current seizure types in six adult patients with HH-epilepsy with video-EEG monitoring, characterized clinical-electrographic features of gelastic and non-gelastic seizures and correlated these findings with cognitive profile, as well as MRI and ictal SPECT data. RESULTS: Only four seizure types were seen: GS, complex partial (CPS), tonic seizures (TS) and secondarily generalized tonic-clonic seizures (sGTC). An individual patient presented either CPS or TS, but not both. GS progressed to CPS or TS, but not both. Ictal patterns in GS/TS and in GS/CPS overlapped, suggesting ictal spread from the HH to other cortical regions. Ictal SPECT patterns also showed GS/TS overlap. Patients with GS-CPS presented a more benign profile with preserved cognition and clinical-EEG features of temporal lobe epilepsy. Patients with GS-TS had clinical-EEG features of symptomatic generalized epilepsy, including mental deterioration. CONCLUSIONS: Video-EEG and ictal SPECT findings suggest that all seizures in HH-related epilepsy originate in the HH, with two clinical epilepsy syndromes: one resembling temporal lobe epilepsy and a more catastrophic syndrome, with features of a symptomatic generalized epilepsy. The epilepsy syndrome may be determined by HH size or by seizure spread pattern.     

Nicotine reinforcement in rats with histories of cocaine self-administration

Few reports have described conditions under which nicotine self-administration occurs in rats. In this study, rats which initially lever pressed for cocaine infusion (0.05 mg/kg) during 1 h experimental sessions continued to obtain similar infusion numbers when nicotine (0.03 mg/kg) was available. When saline was substituted for nicotine, infusions decreased from 11.8±4.5/h to 5.4±1.1/h but returned to pre-saline levels when it was reintroduced (12.0±5.5/h). These results indicate that nicotine can serve as a positive reinforcer for rats under the historical and schedule conditions described.     

Metabolism and pharmacokinetics of p-(3,3-dimethyl-1-triazeno) benzoic acid in M5076 sarcoma-bearing mice

Summary The pharmacokinetics of the anticancer agent p-(3,3-dimethyl-1-triazeno) benzoic acid (pCOOH-DMT), a drug now in phase I clinical trial in Europe, was investigated in C57 Bl female mice with M5076 reticulum-cell sarcoma that were treated i.v. with 200 mg/kg pCOOH-DMT. The drug disappeared from plasma with a terminal half-life of about 2.5 h. Plasma clearance was approximately 6 ml/min per kg. Distribution studies showed some differences in drug levels in different tissues. The highest levels were found in the tumor, liver, kidney and lung; lower levels were found in the spleen and gut, and the lowest, in the brain. The N-desmethyl derivative of pCOOH-DMT was not detectable in plasma or tissues of mice treated with the drug. Therefore, the previous evidence of low N-demethylation of pCOOH-DMT was confirmed. pCOOH-DMT glucuronide was identified by mass spectrometry and quantified by high-performance liquid chromatography (HPLC) in plasma, tissues and urine samples. pCOOH-DMT glucuronide appears to be the major urinary metabolite of pCOOH-DMT in mice. Another metabolite identified by mass spectrometry and quantified by HPLC in some tissues and urine was pCOOH-DMT glycinate.Abbreviations DTIlC 5-(3,3-dimethyl-l-triazeno)imidazole-4-carboxamide - pCOOH-DMT p-(3,3-dimethyl-l-triazeno)benzoic acid - pCOOH-MMT p-(3-methyl-l-triazeno)benzoic acid - pCONH₂-DMT p-(3,3-dimethyl-l-triazeno)carboxamide - BSTFA N,O-bis(trimethylsilyl)trifluoroacetamide - TMCS trimethylchlorosilane - TLC thin-layer chromatography - FAB fast atom bombardment - EI electron impact - M5 M5076 reticulum-cell sarcoma - t_1/2 beta-half-life - C₀ concentration time 0 - AUC area under the concentration vs time curve - Cl total clearance - V volume of distribution     

A comprehensive in vitro characterization of pancreatic ductal carcinoma cell line biological behavior and its correlation with the structural and genetic profile

There are a large number of stable pancreatic ductal carcinoma cell lines (PDCL) that are used by researchers worldwide. Detailed data about their differentiation status and genetic alterations are present in the literature, but a systematic correlation with cell biological behavior is often lacking. PDCL (n=12) were clustered by source of tumor cell (ascites, primary tumor, metastasis), and the data of functional cell biology were correlated with the reported structural and genetic profiles. Major histocompatibility complex expression, chemosensitivity and aneuploidia appeared to be related to the source of PDCL, and proliferative capacity appeared to be related to the grade of differentiation. No correlation between genetic/structural features of PDCL and biological behavior was found. All the cell lines appeared generally insensitive to in vitro treatment with 5-fluorouracil and showed variable degrees of susceptibility to gemcitabine, raltitrexed and oxaliplatin. All the PDCL showed resistance to Fas-mediated apoptosis but were significantly sensitive to the pro-apoptotic effect of inflammatory cytokines [interleukin (IL)-1, tumor necrosis factor (TNF) and interferon ]. PDCL were characterized for the secretion of several factors relevant to the tumor-immune cross talk. Vascular endothelial growth factor, CCL2, CCL5 and transforming growth factor were the factors most frequently released; less frequent was the secretion of CXCL8, CCL22, IL-6 and sporadically CXCL12, IL-10 and hepatocyte growth factor. The cytokines IL-1 and TNF were always undetectable. In conclusion, a clear correlation between structural/genetic features and function could not be detected, suggesting the weakness of a morphological classification for the in vitro studies of pancreatic cancer.     

Mapping of MRX81 in Xp11.2-Xq12 suggests the presence of a new gene involved in nonspecific X-linked mental retardation

X-linked nonspecific mental retardation (MRX) accounts for approximately 25% of mental retardation in males. A number of MRX loci have been mapped on the X chromosome, reflecting the complexity of gene action in central nervous system (CNS) specification and function. Eleven MRX genes have been identified, but many other causative loci remain to be refined to the single gene level. In 21 MRX families, the causative gene is located in the pericentromeric region; and we report here the identification by linkage analysis of a further such locus, MRX81. The new MRX locus was identified by two- and multi-point parametric analysis carried out on a large Italian family. Tight linkage of MRX81 to DNA markers ALAS2, DXS991, and DXS7132 was observed with a maximum LOD score of 3.43. Haplotype construction delineates an MRX81 critical region of 8 cM, the smallest MRX pericentromeric interval so far described, between DXS1039 and DXS1216, and placing it in Xp11.2-Xq12. So far, automated sequencing of two candidates in the region, the MRX gene oligophrenin (OPHN1) and the brain-specific ephrinB1 (EFNB1) gene, in DNA from affected males excluded their candidacy for MRX81, suggesting a novel disease gene.