Early-stage cervical carcinoma, radical hysterectomy, and sexual function. A longitudinal study

BACKGROUND: Limited knowledge exists concerning the impact of radical hysterectomy (RH) alone on the sexual function of patients with early-stage cervical carcinoma. The authors investigated the longitudinal course of self-reported sexual function after RH. METHODS: The current study was comprised of 173 patients with lymph node-negative, early-stage cervical carcinoma who had undergone RH and pelvic lymphadenectomy. They were assessed prospectively using a validated self-assessment questionnaire 5 weeks and 3 months, 6 months, 12 months, 18 months, and 24 months after RH. Results were compared with an age-matched control group from the general population. RESULTS: Compared with control women, patients experienced severe orgasmic problems and uncomfortable sexual intercourse due to a reduced vaginal size during the first 6 months after RH, severe dyspareunia during the first 3 months, and sexual dissatisfaction during the 5 weeks after RH. A persistent lack of sexual interest and lubrication were reported throughout the first 2 years after RH. Long-term lack of sexual interest and insufficient vaginal lubrication were confirmed by the patient's self-reported changes 12 months after RH compared with before the cancer diagnosis and by a pre-post comparison within patients. However, most of the patients who were sexually active before their cancer diagnosis were sexually active again 12 months after surgery (91%), although with a decrease in sexual frequency reported. CONCLUSIONS: RH had a persistent and negative impact on patients' sexual interest and vaginal lubrication whereas the majority of other sexual and vaginal problems disappeared over time. Sexual and vaginal problems in the short-term and long-term after RH should be discussed with the patient before and after surgery.     

Fate of branch arteries after intracranial stenting

OBJECTIVE: One concern with respect to stent procedures performed to treat patients with intracranial lesions is the fate of normal major arterial branches after stents are placed across them. Because most of these lesions occur at vessel bifurcations or at branch points, a normal major branch often arises near the lesion and may be difficult to avoid during stent positioning. The aim of this article is to describe the angiographic outcome of intracranial major branch arteries crossed by a stent in the intracranial circulation. METHODS: We examined the immediate postprocedural cerebral angiograms of the 40 patients who underwent intracranial stenting at the University at Buffalo, Buffalo, NY, between June 1998 and April 2000. In each of 10 patients, the stent was placed across a normal major branch artery. Stents were used to treat aneurysms in seven patients and intracranial stenosis in three patients. The latest cerebral angiogram available was reviewed, and the patency of the major branch arteries was evaluated. RESULTS: The angiographic follow-up period ranged from 4 days to 35 months (mean follow-up, 10 mo). Each of the 10 major branch arteries was patent. No infarcts were associated with the territory of the major branch arteries crossed by the stents, and no patient experienced a related episode of clinical ischemia. Four patients died as a result of causes unrelated to the stenting procedure. The histology of a middle cerebral artery stent that was placed across a lenticulostriate perforator is presented. CONCLUSION: The flexible, low-profile stents used in this study had no angiographically or clinically apparent effect on the major intracranial branches across which they were placed.     

Searching for moderators and mediators of pharmacological treatment effects in children and adolescents with anxiety disorders

OBJECTIVE: To examine whether age, gender, ethnicity, type of anxiety disorder, severity of illness, comorbidity, intellectual level, family income, or parental education may function as moderators and whether treatment adherence, medication dose, adverse events, or blinded rater's guess of treatment assignment may function as mediators of pharmacological treatment effect in children and adolescents with anxiety disorders. METHOD: The database of a recently reported double-blind placebo-controlled trial of fluvoxamine in 128 youths was analyzed. With a mixed-model random-effects regression analysis of the Pediatric Anxiety Rating Scale total score, moderators and mediators were searched by testing for a three-way interaction (strata by treatment by time). A two-way interaction (strata by time) identified predictors of treatment outcome. RESULTS: No significant moderators of efficacy were identified, except for lower baseline depression scores, based on parent's (but not child's) report, being associated with greater improvement (p < .001). Patients with social phobia (p < .05) and greater severity of illness (p < .001) were less likely to improve, independently of treatment assignment. Blinded rater's guess of treatment assignment acted as a possible mediator (p < .001), but improvement was attributed to fluvoxamine, regardless of actual treatment assignment. Treatment adherence tended to be associated (p = .05) with improvement. CONCLUSIONS: In this exploratory study, patient demographics, illness characteristics, family income, and parental education did not function as moderators of treatment effect. Social phobia and severity of illness predicted less favorable outcome. Attribution analyses indicated that study blindness remained intact. The presence of concomitant depressive symptoms deserves attention in future treatment studies of anxious children.     

Probes for narcotic receptor mediated phenomena. 12. cis-(+)-3-Methylfentanyl isothiocyanate, a potent site-directed acylating agent for delta opioid receptors. Synthesis, absolute configuration, and receptor enantioselectivity

The first enantiomeric pair of irreversible opioid ligands [(+)- and (-)-4] were synthesized in greater than 99.6% optical purity as determined by HPLC analysis of diastereoisomeric derivatives of the intermediate 3-methyl-N-phenyl-4-piperidinamine enantiomers. Single-crystal X-ray analysis of the (R,R)-L-(+)-tartaric acid salt of (-)-9 revealed the absolute configuration to be 3S,4R. The absolute configuration of (-)-3 [cis-(-)-3-methylfentanyl] and (-)-4 derived from (-)-9 is thus 3S,4R and that of (+)-3 and (+)-4 is 3R,4S. The (+) enantiomer of 4 (SUPERFIT) was shown to be highly potent and specific for acylation of delta opioid receptors (to the exclusion of mu) in rat brain membranes like its achiral prototype FIT and was about 10 times as potent as the latter in this assay. The (+)-4 was about 5 times as potent as FIT in acylation of delta receptors in NG108-15 neuroblastoma X glioma hybrid cells and about 50 times as potent as its enantiomer. Both FIT and (+)-4 behaved as partial agonists in inhibition of delta receptor coupled adenylate cyclase in NG108-15 membranes and (+)-4 was 5-10 times more potent than FIT and about 100 times more potent than its enantiomer in this assay. Dibromination of amine 12, catalytic exchange of bromine with tritium gas, and reaction of the labeled amine with thiophosgene afforded [3H]-(+)-4 with a specific activity of 13 Ci/mmol. Previous experiments indicated (+)-4 acylates the same 58 000-dalton glycoprotein previously shown to be acylated by FIT but with less nonspecific labeling. In view of the high potency and specificity of (+)-4 and the availability of its enantiomer, it seems likely that these compounds will prove to be valuable tools for study of the opioid receptor complex.     

Unvernetzte epoxide-amin-additionspolymere, 32. Hochmolekulare polykationen vom michler-hydrolblau-typ und ihre dielektrische charakterisierung

A high-molecular-weight poly(leuco base) (M _n = 11000–18000) was obtained by addition polymerization of N,N′-dibenzyl-4,4′-methylenedianiline ( 2 ) and 2,2-bis[4-(2,3-epoxypropoxy)-phenyl]propane (diglycidyl ether of Bisphenol A) ( 1 ). The oxidation of this addition polymer with chloroanil, iodine, bromine, chlorine or antimony pentachloride results in polymeric dyes (absorption at λ = 620 nm) containing units of the “Michler Hydrolblau” type. The dielectric behavior in the frequency range 10² Hz up to 10⁷ Hz shows a dependence of the conductivity on the temperature. Polymer 4c exhibits a conductivity of σ = 6 · 10^?6 S/cm at 134,3°C and 10⁶ Hz.     

Tumor necrosis factor in advanced colorectal cancer: a phase II study. A trial of the phase I/II study group of the Association for Medical Oncology of the German Cancer Society

In a phase II study, the efficacy and toxicity of human recombinant tumor necrosis factor (rh TNF-alpha) were evaluated in patients with advanced colorectal carcinoma. Rh TNF-alpha was given as short term infusion at a dose of 3 x 10(5) U/m2 on three successive days. Treatment was repeated after a two week interval. The response was evaluated after four treatment cycles. In 15 patients entering the study, we found one partial response, one stable disease, 9 progressive diseases, and four patients who were not evaluable for tumor remission. There were numerous side effects of the treatment, mainly fever, chills, loss of appetite, leukopenia, and hepatotoxicity. In this regimen, rh TNF-alpha does not suggest a therapeutic advantage for treatment of advanced colorectal carcinoma.     

IFN-α-Konsolidierung nach intensiver Chemotherapie bringt keinen Überlebensvorteil bei niedrigmalignen Non-Hodgkin-Lymphomen

Strahlentherapie und Onkologie -     

Valproate enhances inhibitory postsynaptic potentials in hippocampal neurons in vitro

Effects of sodium valproate (0.5-10 mM) on hippocampal cells (CA3 pyramidal cells and granule cells) of the guinea pig in vitro were studied by intra- and extracellular recording. Inhibitory postsynaptic potentials were markedly and reversibly augmented. Their shunting action as well as duration increased by more than 150%. Effects of locally administered gamma-aminobutyric acid (GABA) did not change significantly. Membrane characteristics such as membrane potential, membrane input resistance and action potential did not alter. Valproate suppressed spontaneous spiking and repetitive discharges evoked by GABA antagonists. It is concluded that valproate enhances GABAergic synaptic transmission by a presynaptic mechanism. However, postsynaptic mechanisms might be involved in the limitation of repetitive firing.