Serum epidermal growth factor receptor levels in patients with malignant melanoma.

BACKGROUND: Epidermal growth factor receptor (EGFR) is known to be abnormally expressed in many human carcinomas, suggesting that there may be an increase in serum EGFR levels in patients with malignant melanoma (MM) and that this might be a possible new tumour marker. AIM: To assess whether serum EGFR levels might be a marker of MM. METHODS: Serum samples were obtained from 66 patients with MM and 12 healthy controls, and EGFR levels were measured by double-determinant ELISA. RESULTS: Patients with in situ or stage I MM had significantly higher serum EGFR levels compared with healthy controls. Interestingly, serum EGFR levels decreased gradually with the stage of the tumour, being highest at stage I and lowest at stage IV. There was also a trend towards a reverse correlation between tumour thickness and serum EGFR levels. Moreover, a longitudinal study identified a trend for serum EGFR levels in patients with preoperative MM to decrease compared with patients with recurrent MM. CONCLUSIONS: To our knowledge, this is the first report investigating the serum EGFR levels of patients with MM, and gives new insight into the relationship between EGFR and MM. We found that serum EGFR levels were significantly increased in patients with early-stage MM such as in situ and stage I tumours. Measurements of serum EGFR levels might be of clinical value in the detection of early-stage MM.

Ictal SPECT of thalamocortical coupling in a patient with frontal absence.

Petit mal absence has been reported with 3-Hz generalized spike-and-wave discharges induced by secondary bilateral synchrony. Absence seizure may be present in patients with frontal lobe epilepsy. The thalamic rhythmogenic mechanisms responsible for spike-and-wave discharges have been investigated, providing a better understanding of the underlying anatomico-physiological mechanisms. We report the thalamocortical coupling in a patient with frontal absence by performing synchronous ictal single photon emission computed tomography (SPECT) analysis. Ictal SPECT revealed thalamic hyperperfusion combined with ipsilateral frontal cortical hyperperfusion in the patient. Moreover, lateral indexes of cerebral blood flow in the frontal region and thalamus were higher than those from non-epileptic control subjects. Thalamocortical coupling was thus revealed by ictal SPECT. Frontal absences should be considered as a secondarily generalized epilepsy syndrome originating from the frontal regions. The thalamus may play a crucial role as a pacemaker of rhythmic electroencephalographic activities such as secondary bilateral synchronous discharges in patients with frontal absences.

Prefrontal lobe growth in a patient with continuous spike-waves during slow sleep.

Epilepsy with continuous spike-waves during slow sleep (CSWS) is characterized by impairment of neuropsychological abilities, frequently associated with behavioral d isorders. These manifestations strongly correlate with frontal lobe dysfunctions. In the present case, an 11-year-old girl presented with progressive behavioral deteriorations after the appearance of electrical status epilepticus in sleep. The duration of CSWS period was 5 months. Serial measurements (at the appearance of the EEG pattern, and 6 months and 1, 2, 3 and 4 years thereafter) of frontal and prefrontal lobe volumes by 3-dimensional magnetic resonance imaging-based volumetry showed growth disturbance of prefrontal lobe volume, particularly prefrontal-to-frontal lobe volume ratio, after the appearance of the EEG pattern when compared with two frontal lobe epilepsy subjects without neuropsychological disorders and 13 control subjects. However, the ratio was restored to the growth ratio and seen to reach control levels, after improvement of the clinical manifestations of CSWS. These results suggest that children with CSWS may be prone to frontal lobe dysfunctions, and that the duration of CSWS period seems to be a significant prognostic factor. The urgent suppression of this EEG abnormality may be necessary to prevent the progression of neuropsychological impairments.

PTEN mutations in malignant gliomas and their relation with meningeal gliomatosis.

A putative tumor suppressor, the PTEN gene at chromosome 10q23. was identified and found to be mutated in many different human tumors. PTEN was recently found to be also involved in focal cell adhesion and cell migration. To identify the role of PTEN gene in malignant gliomas. we used PCR-SSCP and direct sequencing methods to examine 44 malignant gliomas comprising 29 cases without and 15 cases with meningeal gliomatosis. In malignant gliomas without meningeal gliomatosis, 2/29 (7%) of the cases showed alteration of the PTEN gene. In contrast, 5/15 (33%) of malignant gliomas with meningeal gliomatosis cases showed this alteration. These findings indicate that PTEN gene mutation contributes not only to the neoplastic evolution in gliomas but also to the meningeal dissemination of glioma cells.

[Developmental changes of awareness during passive and active attentions: evaluation of serial event-related potentials (N130, N180, P250)].

Serial event-related potentials (ERPs), especially the negative components before P300, were recorded to evaluate the developmental changes of awareness, or intentional attention. In this study, 36 healthy children (5-16 years of age) and eight healthy adults (19-37 years) were told to perform two attentive paradigms: passive and active. Each test condition consisted of 16 electrical stimuli. Four trials were averaged in sequence and then evaluated as serial four blocks. With repetition in both passive and active attentive paradigms the amplitude of N130 was not attenuated until six years old. During active attention, N180 remained undiminished in adolescents and adults. The amplitude of P250 decreased with repetition during passive attention in children over seven years old, but was not attenuated during active attention in adults. These results suggest that N130 reflects the orienting reflex, and that N180 is associated with the process to maintain awareness.

[Quantitative measurement of prefrontal lobe volume on three dimensional magnetic resonance imaging scan].

This article describes the measurement of the frontal and prefrontal lobe volumes on three dimensional (3-D) MRI in 13 children aged 5 months to 14 years and in 3 adults aged 27 to 39 years. The 3-D MRI data were acquired by the fast spoiled gradient recalled (SPGR) sequence using a 1.5 T MR imager. The frontal and prefrontal lobe volumes were measured by the volume measurement function of the Workstation. We confirmed that this technique to analyze segmental brain volumes achieved acceptable levels of reliability and accuracy. There was an increase in the frontal and prefrontal lobe volumes with advancing age, being rapid between 8 and 15 years of age. The prefrontal to frontal lobe volume ratio also increased gradually, with spurts between 8 and 15 years of age. This approach may be particularly useful for studies on patients with frontal and prefrontal lobe dysfunctions.

[Clinical and bacteriological evaluation of ceftriaxone (CTRX) dosed once daily in children with community-acquired pneumonia].

Clinical and bacteriological evaluation was performed as follows on ceftriaxone (CTRX) at a dose of 50 mg/kg once daily to pediatric patients with community-acquired pneumonia. Of 48 subject patients, CTRX was markedly effective in 36 (75.0%), effective in 9 (18.7%), slightly effective in 2 (4.2%), and failure in 1 (2.1%), indicating the overall effective rate of 93.7%. In 47 (97.9%) patients with the exception of 1, it was observed during the period of administration that fever was resolved and clinical symptoms as well as radiographically abnormal shadows were found relieved or improved. Patients infected by an isolated strain accounted for 34 (70.8%), while those by multiple strains 14 (29.2%), indicating that either Streptococcus pneumoniae or Haemophilus influenzae, or both were detected in almost all patients (45 cases). Of the 48 patients, bacteriological effect was eliminated in 44 (91.7%), and replacement of the bacteria in the remaining 4 (8.3%). MIC90 of CTRX against detected bacteria was 0.2 microgram/ml with H. influenzae, < or = 0.025 microgram/ml with PSSP, 0.1 microgram/ml with PISP, and 0.39 microgram/ml with PRSP. Blood concentration of CTRX at 50 mg/kg upon completion of 1-hour drip intravenous infusion was 89.7 +/- 25.2 micrograms/ml, and 6.6 +/- 0.9 micrograms/ml at 24 hours after the completion, indicating that the concentrations had been well above the levels of MIC90 throughout the 24 hours. Abnormal symptoms, which were most likely adverse drug reactions, were not observed in any patients, and no abnormal changes were noted in patients, whose clinical lab values were taken before or after the administration. Situations may differ by region in Japan, however, infants under 3 are generally exempted from medical payment regardless of inpatients or outpatients. When hospitalized, psychological burden upon pediatric patients without guardians attended must be enormous. If they are over 3, there is a difference in medical costs between inpatients and outpatients, with greater economic burden on inpatients. Thus, it was considered worth attempting the outpatient treatment as one of new therapies for community-acquired pneumonia, though the outpatient treatment should not be encouraged without due consideration. Based on these results, CTRX dosed once daily to pediatric patients with community-acquired pneumonia is clinically and bacteriologically superior in usefulness. Further review may be necessary, however, it is considered that outpatient treatment can also serve as one of the options, if safety of once-a-day administration of CTRX can be established.

[Electrophysiologic evaluation of passive and active attentions--I. Topographic analysis of somatosensory event-related potentials].

We studied the topography of somatosensory event-related potentials (SERP) in two different attentive conditions: passive and active. Seventeen healthy right-handed young men, aged 19 to 28 years old (average age; 22.9 years), were requested to perform the following four paradigms in turn. In the passive attentive paradigm, participants were given no specific task when 0.3 Hz electrical stimuli were at random delivered to the right median nerve. In the active attentive paradigm, subjects were required to direct their attention to the regular 0.3 Hz stimuli with all their might. In the control paradigm. 2.0 Hz stimuli were delivered as they listened to their favorite music. Finally, in the oddball paradigm, subjects were instructed to push a button whenever they detected rare stimuli. SERP was recorded at 13 electrodes Grand average topographic amplitude maps from the individual data of the seventeen subjects were made at the latencies of N 60, P 90, N 130 and P 250 for each of the four paradigms. The topographic maps of P 250, the largest positive peak between 200 and 300 msec after the stimuli, showed a significant difference in the distribution of amplitude in the passive and active attentive paradigms compared to the control paradigm. A statistically significant enhancement was noted at the central region in the passive attention, and at the central and frontal regions in the active attention. These results suggest that P 250 consists of two attentive components distinct from selective or discriminative attention. The enhanced positivity at the frontal region during active attention may be associated with expecting the next stimulus and maintaining awareness.

[Electrophysiologic evaluation of passive and active attentions--II. Developmental changes of somatosensory event-related potentials in different attentive paradigms].

By somatosensory event-related potentials (SERP) we have previously demonstrated in adults that an enhanced positivity of P 250 is statistically significant at the frontal region during the active attentive state. We have also evaluated developmental changes of P 250 during different attentive states: passive and active. In this study, 30 healthy children (5-16 years of age) and six healthy adults (23-41 years) were required to perform the following four paradigms: passive attentive, active attentive, control, and oddball. SERP were recorded at Fz, Cz and Pz. In the passive attentive paradigm, P250 amplitude at Fz, Cz and Pz remained constant irrespective of age. With regard to the topography of the amplitude, however, P 250 was distributed dominantly at Pz in Group 1 (5-6 years of age) and Group 2 (7-11 years), contrary to the dominance at Cz in both Group 3 (12-16 years) and adults. In the active attentive paradigm, on the other hand, the P 250 amplitude at Fz reached its minimum at about 10 years and then increased until the adulthood. With respect to the topography of the amplitude, P 250 was distributed dominantly at Pz in Groups 1 and 2, at Cz in Group 3, and at Fz and Cz in adults. These results suggest that the topographic changes in the active attentive paradigm are dependent upon the developing abilities to expect the next stimulus and to maintain awareness.

[Clinical evaluation of faropenem against infections in pediatric fields].

The recent increases in the prevalence of penicillin-resistant Streptococcus pneumoniae becomes a point at issue clinically. We carried out a clinical study in 40 cases in the pediatrics department, as faropenem (FRPM) was proved to have an excellent antimicrobial activity against penicillin-resistant Streptococcus pneumoniae. The study was planned to investigate in detail the movement of stools that had been a problem in a clinical development studies out before. In this study, an observation of the daily movement of stools was one of the principal evaluation items, hence the patients were divided into two groups. One group (S-group) were administered FRPM only, the other group (E-group) were administered FRPM in combination with a medicine for intestinal disorders (Enteronon-R). An observed frequencies of any loose bowel movements were 94.7% in S-group, and 63.2% in E-group, hence the study suggested that the combination drug was effective. The patients observed higher frequencies of development of the movement of stools, all of them were recovered from in the course of administration or within 4 days after administration, however whether or not being treated symptomatic therapy. Clinical efficacy rates of FRPM on mainly respiratory infections were 94.6%. In this study, 4 strains (patients) of penicillin-resistant Streptococcus pneumoniae were isolated. Against penicillin-resistant Streptococcus pneumoniae, FRPM demonstrated more potent antibacterial activity than the oral penicillins and cephems tested here except cefditoren. Clinical efficacies was deemed effective in all of the 4 cases, and bacteriologically, 3 organisms were eradicated. As for side effects including diarrhea and loose stool, no serious side effects were observed. Based on the above results, FRPM is effective against most infections in the pediatric field which Streptococcus pneumoniae are isolated at high frequencies highly, and is considered to cases in be useful an attention will have to be paid to stool movement, however.

[Efficacy and side effects of lidocaine by intravenous drip infusion in children with intractable seizures].

Intravenous drip infusions of lidocaine (IDIL; 1-5 mg/kg/h) were performed in ten patients with intractable seizures. The medication was very effective in five patients, whose seizures disappeared immediately after the treatment of IDIL. In four patients, the medication proved to be effective judging from decreased incidence of seizures. In one patient with intractable seizures, the therapy was not effective. In nine patients with the effective medication, five had generalized seizures and four had partial seizures. Side effects were observed in four patients. Two patients had muscle hypotonia, one had visual and auditory hallucination and another had bradycardia. These symptoms completely disappeared after the ceasing of IDIL. Serum concentrations of lidocaine at the appearance of the side effects ranged from 1.8 to 4.7 micrograms/ml, although the toxicity level is more than 5.0 micrograms/ml for arrhythmic adult patients. These findings suggest that the serum toxic level of lidocaine in children is different from that in adults, and that careful observation and appropriate management for the children with lidocaine therapy should be necessary, even though the serum level of lidocaine ranges within the therapeutic level.

[Cerebral cortical dysplasia associated with epilepsy: MRI and clinical aspects].

Clinical and electroencephalographic (EEG) studies were performed in nine patients with cerebral cortical dysplasia (CD). Interictal single photon emission computed tomography (SPECT) using 99mTc-hexamethyl propylene amine oxime were studied in four patients. A patient with hemimegalencephaly and agyria had poor outcome in both developmental and epileptic aspects. The prognoses of clinical seizures were generally related to the severity, location and size of CD. The size of the lesion was not always correlated with the clinical seizure outcome. Four patients had focal pachygyria. Clinical pictures were diverse in these patients. One patient underwent callosotomy for the control of intractable seizures. The others had no clinical seizures despite of the appearance of paradoxical discharges in the area of pachygyria. The distribution of CD detected by MRI did not always correlate with that of paradoxical discharges in EEG and/or hypoperfusional areas seen in SPECT. These findings suggest that a detailed neuroimaging study is useful to elucidate the epileptogenesis in patients with CD, and that all the cortical abnormalities in patients with intractable epilepsy are not detected by MRI.

[A successful treatment with a continuous intravenous lidocaine for a cluster of minor seizures in a patient with Doose syndrome].

We reported a 7-year-old girl with myoclonic-astatic epilepsy of early childhood (Doose syndrome). She had minor seizures (i. e. absence, atonic and myoclonic seizures) refractory to treatment with many kinds of anti-epileptic drugs as well as thyrotropin releasing hormone. Though she had suffered from long-lasting clusters of minor seizures, the treatment with continuous intravenous lidocaine successfully brought a case of prolonged remission of both clinical seizures and EEG abnormalities. It has been reported that lidocaine is effective mainly for partial seizures. The efficacy of lidocaine for generalize seizures, however, has been reported only in a few papers. We considered that the treatment with continuous intravenous lidocaine is indicated in patients with Doose syndrome presenting with a cluster of refractory minor seizures.

[Electrophysiological studies of a case of startle disease].

A 53-year-old female with startle disease (major form) was reported. An abnormal startle response was the most prominent clinical feature. Physical examination revealed left lateral gaze palsy and left extensor plantar response. The caloric test evoked no responses bilaterally. Blood examinations including lysozomal enzymes and radiological examinations including MRI of the brain were all normal. A pathological startle reflex was elicited by the tap on the upper lip, causing the marked extension of the head with the elbow, hip, and knee joints slightly flexing. The earliest reflex activity in a surface-EMG study was recorded in the masseter muscle and the reflex then spread down the brain stem and the spinal cord. The duration of the discharge varied from 16 to 30 ms. The onset latencies of these responses from the tap were 11.2 ms, 12.7 ms, 14.5 ms, 25.7 ms, 38.5 ms, and 47.5 ms in the masseter, sternocleidomastoid, posterior-neck, biceps brachii, quadriceps femoris, and tibialis anterior muscle, respectively. An averaged electroencephalogram triggered by the taps showed no abnormal EEG activity preceding the pathological startle response, although a negative peak, which was thought as a normal early component of the trigeminal somatosensory evoked potentials, was followed by the reflex. High amplitude SEPs and long loop reflexes were observed following stimulation of the posterior tibial nerve but not of the median nerve. Blink reflexes and auditory evoked potentials were normal.(ABSTRACT TRUNCATED AT 250 WORDS)