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Biomedical subjects

R Kan

Publications and source records attributed to R Kan.

At least 19 recordsLinked to original sources
PubMed1999

Congenital malformations due to antiepileptic drugs.

To identify the major risk factors for the increased incidence of congenital malformations in offspring of mothers being treated for epilepsy with antiepileptic drugs (AEDs) during pregnancy and, to determine the relative teratogenic risk of AEDs, we prospectively analyzed 983 offspring born in Japan, Italy, and Canada. The incidence of congenital malformations in offspring without drug exposure was 3.1%, versus an incidence with drug exposure of 9.0%. The highest incidence in offspring exposed to a single AED occurred with primidone (PRM; 14.3%), which was followed by valproate (VPA; 11.1%), phenytoin (PHT; 9.1%), carbamazepine (CBZ; 5.7%), and phenobarbital (PB; 5.1%). The VPA dose and level positively correlated with the incidence of malformations. This study first determined a cut-off value of VPA dose and level at 1000 mg/day and 70 microg/ml, respectively, to avoid the occurrence of malformations. The incidence of malformations increases as the number of drugs increases, and as the total daily dose increases. Specific combinations of AEDs such as VPA + CBZ and PHT + PRM + PB produced a higher incidence of congenital malformations. The incidence of malformations was not associated with any background factors studied except for the presence of malformations in siblings. These results indicate that the increased incidence of congenital malformations was caused primarily by AEDs, suggesting that malformations can be prevented by improvements in drug regimen, and by avoiding polypharmacy and high levels of VPA (more than 70 microg/ml) in the treatment of epileptic women of childbearimg age.

Abnormalities, Drug-Induced↗
PubMed1999

Intrauterine growth in the offspring of epileptic women: a prospective multicenter study.

The aim of the present study was to evaluate the risk of intrauterine growth delay in the offspring of epileptic mothers and to quantify the risks of intrauterine exposure to antiepileptic drugs (AEDs). Data concerning 870 newborns, prospectively collected in Canada, Japan and Italy, using the same study design, were pooled and analyzed. The overall proportion of newborns whose body weight (7.8%) or head circumference (11.1%) at birth were below the 10th percentile was not increased. However, logistic regression analysis showed that the risk of small head circumference was significantly higher in Italian than in Japanese (RR 4.2; 95% CI: 2.2-8.0) or Canadian children (RR 2.6; 95% CI: 1.1-6.5), and in children exposed to polytherapy (RR 2.7; 95% CI: 1.2-6.3), phenobarbital (PB) (RR 3.6; 95% CI: 1.4-9.4) and primidone (PRM) (RR 4.5; 95% CI: 1.5-13.8). Country was also the only factor affecting low body weight, with Italian children having a higher risk than Japanese (RR 5.2; 95% CI: 2.6-10.4) or Canadian (RR 8.8; 95% CI: 2.0-38.1) children. Due to the small categories, the influence of AED doses and plasma concentrations was studied for each individual AED, without adjustment for the other potential confounding factors. A clear dose-dependent effect was found for PB and PRM in terms of both small head circumference and low body weight, and a concentration-dependent effect for PB in terms of small head circumferences. The size of the difference between the Italian and the other two populations, which is only partially explained by differences in therapeutic regimens, suggests that genetic, environmental and ethnic factors also need to be taken into account when considering possible explanations.

Anticonvulsants↗
PubMed1997

Predictors of bone mineral loss in patients with ovarian cancer treated with anticancer agents.

OBJECTIVE: To identify factors predicting bone mineral loss during anticancer chemotherapy. METHODS: Fifteen women (mean age 38.2 +/- 7.8 years; range 30-46 years) with ovarian cancer who had been treated with cisplatin-adriamycin-cyclophosphamide for six cycles every 4 weeks following surgical cytoreductin were studied. Bone mineral density (BMD) of the lumbar spine (L2-L4) was measured by dual-energy x-ray absorptiometry before and after chemotherapy. Fifteen age-matched women whose ovaries had been removed surgically for other reasons. served as controls. None of the patients had received hormonal treatment. The two groups were compared for percentage change of BMD (BMD%) over the same period. In the chemotherapy group, total fat mass, body fat ratio, total lean mass, percent lean, and ration of trunk fat to leg fat were measured by dual-energy x-ray absorptiometry. Lean loss during chemotherapy was also calculated. These variables were compared before and at the end of chemotherapy. Possible correlations of baseline variables with BMD% were determined in univariate and stepwise regression analysis. RESULTS: Mean ( +/- standard deviation) BMD decreased to 87.4 +/- 2.1% after six cycles of chemotherapy and 97.6 +/- 0.4% after 6 months in controls, but the greatest decrease was observed in the chemotherapy group (P < .001). Although baseline lean mass, baseline BMD, body weight, and lean loss during chemotherapy were correlated with BMD% in univariate analysis, baseline lean mass was still significant in stepwise regression analysis. CONCLUSION: Baseline lean mass predicts bone mineral lose with anticancer chemotherapy.

Adult↗
PubMed1997

Echographia as a symptom of interictal state in an epileptic patient: a case report.

Echographia is a phenomenon in which a patient continuously translates verbal stimuli into writing. We encountered a patient with epilepsy who developed visual echographia during interictal periods. In this case, echographia was observed during two different periods, namely the period of disturbed consciousness after the epileptic seizure and the period of clear consciousness after suppression of the seizures. Disinhibition due to disturbance of the consciousness is considered to have been the cause of echographia in the former period. In the latter period, it is considered that echographia was caused by the release of lower function from suppression of upper function by brain dysfunction, as the after effect of status epilepticus. As echographia can be observed in epileptic patients, attention and careful observation by epileptologists is needed.

Adolescent↗
PubMed1994

Serial changes of n-isopropyl-p-iodoamphetamine single photon emission computed tomography in two epileptic psychotics.

Serial changes of single photon emission computed tomography (SPECT) in two epileptic psychotics are reported. One patient had a decreased blood flow of the left temporal lobe with schizophrenia-like symptoms, and the other patient had a decreased blood flow of the right temporal lobe with depressive symptoms. In each case, these abnormal findings disappeared following recovery from a psychotic state. It might be suggested that the psychotic state of an epileptic patient influences the SPECT findings.

Adult↗
PubMed1992

Cytophotometric analysis of magnocellular azure B-RNA and Feulgen-DNA following chronic GABA infusion into the nucleus basalis of rats.

This investigation was undertaken to examine possible cytopathic effects of GABA infusion on nucleus basalis (NBM) magnocellular neurons. Sixty-three male Long-Evans rats received unilateral, intra-NBM infusions of either GABA100 (100 micrograms/microliters/h), GABA10 (10 micrograms/microliters/h), or ultrafiltered saline (1 microliter/h) for a period of 24 hours. Rats from each of these groups were sacrificed at either 24 hours, 48 hours or 8 days following initiation of infusions. The sham operated hemisphere of each rat served as a control for the infused hemisphere. After stoichiometric azure B-RNA and Feulgen-DNA staining of brain sections, scanning-integrating microdensitometry was used to quantify GABA-induced alterations in these well established indices of neuronal toxicity. These results provide evidence that the neurotoxic effects of 24 hours of 100 micrograms/microliters-h GABA infusion are manifested within 48 hours post-initiation of infusions. Although 24 hours of 10 micrograms/microliters-h GABA infusion suppressed NBM neuronal metabolism, the lower magnitude and duration of this effect signified an impending recovery. GABA infusion resulted in little if any NBM neuronal chromatin template impairment (i.e., reduced Feulgen-DNA reactivity), irrespective of the dosage employed and the delay prior to sacrifice.

Analysis of Variance↗
PubMed1992

Serial changes of SPECT in periodic synchronous discharges in a case with Creutzfeldt-Jakob disease.

We conducted serial EEG and SPECT studies on one female with Creutzfeldt-Jakob disease (CJD). In an analysis of EEG, a periodic synchronous discharge (PSD) was observed in the middle of the third stage (terminal stage) of Bernoulli's classification. The frequency of PSD was the highest at the beginning of the third stage, followed by a gradual decrease and disappeared at the end of the third stage. In the middle of the third stage, SPECT disclosed blood flow differences between the cerebrum and other regions (the cerebellum and the brainstem), while no such difference was observed by SPECT at the end of the third stage. It was suggested that the appearance of PSD requires the presence of a pathological change in the cerebrum precedent to other regions.

Aged↗
PubMed1992

Malformation in infants of mothers with epilepsy receiving antiepileptic drugs.

To assess the relative contribution of antiepileptic drugs (AEDS) to occurrence of congenital malformations, we compared two prospective studies. We analyzed data for 14 AEDs for total daily doses (drug score) and eight background factors. From the first study, the drug score and polytherapy--particularly the use of valproate plus carbamazepine--were suspected to be primary factors for increased incidence of congenital malformation. In the other study, the drug score for each case was decreased, and polytherapy--particularly valproate plus carbamazepine--was changed to monotherapy before conception. These changes significantly decreased the incidence of malformations. Among risk factors, only the doses of methylphenobarbital for mothers of infants with malformations were significantly higher than those for mothers of infants without malformations. Statistical differences were seen in drug score, number of AEDs, maternal age at delivery, seizure type, and etiology of epilepsy between the two groups. When data were corrected for seizure type, maternal age at delivery, or etiology of epilepsy, the difference in the incidence of malformations did not disappear, but it did disappear when data were corrected for drug score or number of AEDs. These results support our previous observations that AEDs are primary factors for the increased incidence of congenital malformation in infants of mothers with epilepsy.

Abnormalities, Drug-Induced↗
PubMed1991

A new membrane-associated Ca(2+)-binding protein of rat spermatogenic cells: its purification and characterization.

A Ca(2+)-binding protein of Mr = 52000, estimated by SDS-PAGE, was purified to a final yield of 0.04% from rat spermatogenic cells. Purification steps included gel filtration, ammonium sulfate precipitation and HPLC. Amino acid analysis showed the content of 34% acidic residues and 15% basic residues. The isoelectric point of this protein was 4.7. Dot-blot analysis indicated that the Ca(2+)-binding protein bound 2 mol of calcium per mol of protein. This protein had two binding sites with dissociation constants of 4.8 microM and 0.2 microM. No appreciable amount of hexose was observed (less than 1 microgram of hexose/70 micrograms of protein). This protein may play an important role such as the Ca(2+)-transport in the plasma membrane of spermatogenic cells.

Amino Acids↗
PubMed1991

Intestinal absorption of linoleic acid in experimental renal failure.

Linoleic acid (LA) transport in rats with experimental short-term and long-term renal failure (RF) was compared with that of sham-operated normal animals on liberal food intake and pair-fed animals. The perfusions in vivo and incubations in vitro were conducted using a micellar solution containing a wide range of LA concentrations. Both absorption in vivo and uptake in vitro of LA were significantly reduced in animals with short-term RF. Lipid extraction and separation by thin-layer chromatography revealed a marked LA trapping as trilinolein (TL) in the perfused intestinal tissue in the short-term RF group. The esterification process, as defined by the rate of LA incorporation into TL, was moderately reduced in short-term RF animals. The thickness of the unstirred water layer showed no significant difference among the groups studied. In contrast, animals with long-term RF exhibited normal absorption of LA in vivo at all concentrations tested. In conclusion, LA absorption is reduced in short-term RF and restored in long-term RF. Several steps including LA transport into and TL transport out of the enterocyte and the esterification process were impaired in short-term RF. These changes are not due to alteration in the unstirred water layer, anorexia, weight loss or a rapid effect of uraemic chemical environment or circulatory factors.

Animals↗