New Types of Germacranolides from Austroliabum candidum1.

The investigation of AUSTROLIABUM CANDIDUM afforded, in addition to several known sesquiterpene lactones, four new ones, including three germacranolides with an ether bridge, as well as an unusual glucoside. The structures were elucidated by spectroscopic methods.     

Multipoint Oncology Teleconference, Japan

This teleconference has been held on a weekly basis (on Thursdayevenings) as a good opportunity for the discussion of importantissues in clinical oncology. Nowadays, this plenary meetingamong the major cancer centers is indispensable for maintainingthe high standard of quality of cancer clinics throughout Japan. Review (November, 2004) November 4: Treatment-resistant cervical cancer (moderated byDr Tanaka,     

Totale mesometriale Resektion

Abdominal radical hysterectomy (Wertheim operation), currently the standard surgical treatment for cervical carcinoma, is based on historical ideas of the female pelvic anatomy and of locoregional tumor spread. Total mesometrial resection (TMMR) uses new insights derived from developmental biology for a new oncological concept of radicality, i.e. resection of a malignant tumor within the borders of the morphogenetic unit of its origin. The morphogenetic uterovaginal unit that relates to the local spread of cervical carcinoma can be deduced from the embryological and fetal development. Anatomical structures that do not belong to this tissue unit can be left in situ despite close proximity to the tumor. When combined with nerve-sparing therapeutic lymph node dissection, TMMR yields a high locoregional control rate without adjuvant radiotherapy and with relatively little treatment-related morbidity.     

Auditory P300 and eye tracking dysfunction in schizophrenic pedigrees

Several psychophysiological abnormalities associated with schizophrenia have been proposed as genetic trait markers of vulnerability to the disorder. Smooth pursuit eye tracking dysfunction and abnormal long latency event-related potentials are the most promising candidates. Both are independent of the effects of psychotropic medication or mental state at the time of testing, and twin studies demonstrate that each has a high level of heritability. Having recorded smooth pursuit eye tracking and event-related potentials in 20 high-density schizophrenic families, we find abnormalities in one or both measures in most of the families studied. The abnormalities, when present, occur in the family members with schizophrenia and other forms of functional psychosis, and they have a bimodal distribution with approximately half the nonschizophrenic relatives also showing eye tracking dysfunction and/or abnormal event-related potentials. Some of these relatives had psychiatric symptoms; others were normal. Our results suggest that psychophysiological examination can help to clarify the boundaries of schizophrenia spectrum disorder. By helping to decide the phenotypic status of nonschizophrenic family members, this should increase the power of DNA linkage studies.     

Invasion of visual cortex by the auditory system in the naturally blind mole rat.

Previously we have shown that the dorsal lateral geniculate body (LGB), which is strictly visual in sighted mammals, receives a strong auditory input in the naturally blind mole rat (Spalax ehrenbergi). Here we show with the 2-deoxyglucose technique and with single-unit recordings that in this species the initially non-degenerated visual cortex, as defined by its connection with LGB, is also activated by the auditory modality. These findings suggest that cross-modal compensation may occur as a natural consequence of the degeneration of a sense organ.     

Thyroid stimulating hormone response to thyrotropin in prepubertal depression

In an effort to evaluate whether differences exist in the hypothalamic-pituitary-thyroid axis of depressed children, a thyrotropin releasing hormone (TRH) stimulation test was administered to 55 prepubertal subjects who were divided into three groups matched for age and sex: a depressed group (endogenous N = 15, nonendogenous N = 15), a psychiatric nondepressed control group (N = 16), and a normal control group (N = 9). Each subject was tested at two dosages of TRH, 2 micrograms/kg and 7 micrograms/kg. Increasing age and female sex were positively correlated with a greater thyroid stimulating hormone (TSH) response. TSH response to TRH was examined with subjects reclassified by severe suicidal ideation, severe aggression, and parental history of alcoholism. Results of this study are contrasted with the adult psychiatric literature.     

Preclinical profile of stereoisomers of the anticonvulsant remacemide in mice

Stereoisomers of remacemide (racemate form) were compared for anticonvulsant efficacy and safety in mice. In the maximal electroshock seizure (MES) test for oral efficacy, the (-) stereoisomer, FPL 14145, was more potent than the racemate or the (+) stereoisomer, FPL 14144. Respective ED50 values (expressed as mg/kg) were: remacemide, 58; FPL 14145, 45; FPL 14144, 79. In 2 of 3 tests for neural impairment, FPL 14145 yielded significantly better therapeutic indices (toxic dose 50/ED50) than the racemate. The margin of safety (estimated median lethal dose ED50) was more favorable for FPL 14144: remacemide, 15.1; FPL 14144, 18.9; FPL 14145, 15.7. The duration of protection against MES indicated the stereoisomers were longer acting than the racemate. After intravenous administration the order of potency against MES was similar: FPL 14145 greater than remacemide greater than FPL 14144. Following daily administration of the oral ED98 for 4 days, with a dose response curve run on day 5, the MES ED50 values for all compounds were increased. The test indicates tolerance. In the pentylenetetrazol infusion test the racemate and FPL 14144 demonstrated more proconvulsant properties than FPL 14145. Intraperitoneal administration of 50 mg/kg or more produced changes in behavior with all compounds. At higher doses the racemate and FPL 14145 elicited more severe symptoms with death at 200 mg/kg.     

Magnetic resonance imaging of the pediatric abdomen.

In many ways, MRI of the pediatric abdomen is in its infancy. Motion will be a problem with most of the current pulse sequences, but the problem appears manageable given many of the newer software options for motion suppression. Faster pulse sequences (approaching CT scan times) will serve to improve image quality and reduce the need for sedation. Identification of a reliable enteric contrast agent probably will expand the current utility of MRI beyond evaluation of solid abdominal viscera. Although preliminary results appear promising, controlled comparative studies are necessary to determine the exact role of MRI in diagnosis and staging of common pediatric abdominal malignancies. The addition of MRI intravenous contrast agents and MR spectroscopy are anticipated to add depth and specificity to the diagnostic potential of this exciting modality.