Combination of irinotecan and etoposide for treatment of refractory or relapsed small-cell lung cancer.

PURPOSE: To determine the response rate, survival, and toxicity of irinotecan (CPT-11), a topoisomerase I inhibitor, combined with etoposide, a topoisomerase II inhibitor, in refractory or relapsed small-cell lung cancer (SCLC). PATIENTS AND METHODS: Twenty-five patients with refractory or relapsed SCLC were entered onto the trial. All 25 patients had been pretreated with some form of cisplatin-based combination chemotherapy and had also received previous etoposide- or anthracyclinecontaining chemotherapy. The median time off chemotherapy was 6.7 months (range, 0.9 to 23.5). Patients were treated at 4-week intervals using CPT-11 (a starting dose of 70 mg/m2 intravenously on days 1, 8, and 15) plus etoposide (80 mg/m2 intravenously on days 1 to 3), with a subsequent dose based on toxicity. In addition, recombinant human granulocyte colony-stimulating factor (rhG-CSF; 2 microg/kg/d) was given from day 4 to day 21, except on the days of CPT-11 administration. RESULTS: All patients were assessable for toxicity and survival. Twenty-four patients were assessable for response. There were 14 partial responses (PRs) and three complete responses (CRs), for an overall response rate of 71% (95% confidence interval, 53% to 89%). The median response duration was 4.6 months. Median survival was 271 days. Major toxicities were myelosuppression (predominantly leukopenia) and diarrhea. Grade 3 to 4 neutropenia and thrombocytopenia occurred in 56% and 20% of patients, respectively. Grade 3 to 4 diarrhea was observed in 4%. There was one treatment-related death due to severe myelosuppression. CONCLUSION: A combination of CPT-11 and etoposide with rhG-CSF support is an active therapy against refractory or relapsed SCLC and deserves to be studied more extensively in a phase III trial.

Developmental changes in electroencephalogram for term and preterm infants using an autoregressive model.

The purpose of the present study was to clarify the developmental changes of electroencephalogram (EEG) background activity in term and preterm infants that take place with increasing conceptional age (CA) through an autoregressive (AR) model. Polygraphical EEG recordings were obtained from 76 healthy term and preterm infants with a CA ranging between 31 and 40 weeks. Decreases in total power and component power of delta were noted with CA during burst activity (BA) in quiet sleep (QS) and during active sleep (AS). Increases in total power and component power of delta were noted with CA during interburst interval activity (IBIA) of QS. Regression analysis (RA) of the information amount (IA) indicated a negative correlation with increasing CA in AS and in the monopolar EEG tracings Fp1, C3, O1 and O2 in BA, and a positive correlation in O1 in IBIA. Regression analysis of the IA of delta indicated a negative correlation with increasing CA in AS and in Fp1, C3, O1 and O2 in BA, and a positive correlation in O1 in IBIA. Regression analysis of the IA of delta indicated a negative correlation with increasing CA in BA and AS. These results showed that the high voltage slow wave component changed to a low voltage slow one with development in AS and that BA was longer in duration and lower in power with increasing CA, while IBIA was shorter in duration and higher in power. In conclusion, significant developmental changes occur in all derivatives of AS. Even though the EEG of BA and IBIA change separately, they are followed by EEG of QS in a continuous pattern.

[Allergic granulomatous angitis with hyper expression of eosinophilic adhesion molecules].

A 43-year-old man who had been treated for bronchial asthma presented with an increase in dry coughing and wheezing for one and a half years. In August 1994, the patient noted progressive dyspnea on exertion. A chest radiograph revealed nodular opacity in the right upper lung field. In November 1994, the patient was admitted to Kinki University Hospital with an erythematous rash on the soles of both feet. Examination of a specimen biopsy of the skin lesion revealed granuloma with eosinophil infiltration. Peripheral blood eosinohilia was noted and a bone marrow examination also revealed an increased level of eosinophils. Another chest radiograph revedaled that the nodular opacity had disappeared and a new bilateral pleural effusion was seen. Eosinophils were the predominant cells in the pleural effusion. the patient's condition was further complicated by myocarditis. Allergic granulomatous angitis (Churg-Strauss syndrome) was diagnosed and steroid therapy was started. After the start of steroid therapy, the skin eruption disappered and the myocarditis became less severe. Symptoms of asthma were also well controlled. The eosinophils had hypersegmented unclei and increased expression of adhesion molecules on their surfaces.

[Non-Fukuyama type merosin-positive congenital muscular dystrophy with delayed muscle fiber type differentiation: a case report].

A patient with non-Fukuyama type merosin-positive congenital muscular dystrophy (nonFCMD) who had severe muscle weakness leading to early death was reported. He was the first product of epileptic mother who had been placed on phenobarbital and phenytoin. The patient had severe respiratory failure and muscle weakness at the neonatal period, and died at 4 months of age. Multiple joint contractures were also noted at birth. Serum creatine kinase was within normal limits (123 IU/l). Electromyography showed a myogenic pattern. Brain computed tomographic (CT) scan and magnetic resonance imaging (MRI) were normal without white matter lucency or pachygyria. Muscle biopsy revealed dystrophic changes and type 2C fiber predominance. Dystrophin, dystrophin-associated glycoproteins and merosin were all positively demonstrated. Although patients with merosin-positive nonFCMD have relatively mild clinical course, our patient had severe muscle weakness with fatal outcome. Defect in muscle fiber maturation and differentiation, such as an increase of undifferentiated type 2C fibers, may be a major factor to influence muscle symptoms in non FCMD.

[Developmental characteristics of topographic EEG in the newborn using an autoregressive model].

Using an autoregressive topographic mapping system, developmental changes in the total power of EEG in quiet and active sleep were studied in 23 normal premature infants aged from 34 to 40 weeks of postconceptional age. Pattern discrimination of topographic EEG between both sleep stages was also made. Tracé alternant patterns in quiet sleep and low voltage irregular patterns in active sleep were analyzed. Topographic maps of one segment (10.24 sec) and 10 segments of EEG showed small peaks in the frontal region and large peaks in the occipital region during both sleep stages, with the total power in quiet sleep exceeding that in active sleep. Total power decreased with increasing postconceptional age. In the pattern discrimination of topographic EEG between both sleep stages, significant differences were noted mainly in the frontal and occipital regions. It was concluded that topographic mapping of EEG disclosed spatial differences in EEG development in the newborn.

[Developmental characteristics of the alpha waves of EEG in normal healthy children].

The records of waking state electroencephalography (EEG) of 1,340 normal children aged from 3 to 12 years were subjected to analysis using an autoregressive model. The results were summarized as follows. (1) 6,814 components of second-order activities were obtained through component analysis of the 1,218 EEG records. The frequency polygons of damping frequency of the second-order component waves verified several modes, each of which was enhanced in the eight frequency ranges. (2) The average percent-power of the alpha-1 waves decreased with increasing ages from 3 years, whereas that of the alpha-2 waves increased. That of the alpha-3 waves showed no change with ages. (3) The average damping times of alpha-2 waves increased with increasing ages. (4) Dominancy in frequency showed a course of two step increments at 3-6 and 10 years of age. The former was chiefly due to the increase in the alpha-1 wave and the latter in the alpha-2 wave. There were no significant increases of alpha-3 waves. (5) By means of EEG pattern discrimination, the differences in alpha components among different age groups were obtained as generalized (Maharanobis') distances. The alpha-1 activity showed a significant difference in amount between the age group of 3-6 years and the other age groups. The alpha-2 activity showed a significant difference in amount between the age group of 10 years and the other age groups. (6) The development of brain activity proceeds faster in the posterior areas and relatively slower in the central areas.

[Developmental characteristics of the beta waves of EEG in normal healthy children].

By the use of an autoregressive (AR) model, development of beta-waves in quantitative EEG parameters was studied in 1,340 normal children aged from 3 to 12 years. The results were summarized as follows. The beta band(13.5-25 Hz) was divided into three frequency ranges; beta-1(13.5-17.4 Hz), beta-2(17.5-21.4 Hz) and beta-3 (21.5-25 Hz) waves. The average power and percent-power of the beta-1 and beta-2 waves increased with advancing age, whereas these of the beta-3 wave showed no change with advancing age. By means of EEG pattern discrimination, critical period of beta band in the developing EEG was observed at the age of 4 years in frontal region, 10 years in central region and 3 to 7 years in occipital region. Those results suggest that the development of beta activity may be faster in frontal, occipital areas and relatively slower in central area.

[An application of autoregressive model to pattern discrimination of brain electrical activity mapping].

We developed a method of illustrating significant regional differences between two records of brain electrical activity mapping (BEAM), using pattern discrimination of autoregressive (AR) EEG analysis. In this study, the EEG data could be objectively reduced to a few AR coefficients, and this statistical method was successfully applied to discrimination of differences in BEAM among records from two or more subjects. A significant difference was illustrated at the right parietal region between two age groups, 6 years and 8 years, in normal children. It was concluded that this new approach of BEAM analysis through a statistical taxonomy was clinically useful for evaluation of the normal development of BEAM in children and for localization of functional brain abnormalities.

[Clinical studies on ceftazidime in the pediatric field].

Ceftazidime ( CAZ ) is a newly developed cephalosporin. Clinical studies on this drug was carried out and the results were as follows. Twenty-nine patients (acute purulent tonsillitis 2, acute bronchitis 1, pneumonia 15, acute purulent lymphadenitis 2, pyoderma 1, skin abscess 2 and urinary tract infection 6) were treated with CAZ in doses of 42-1 mg/kg (mean 59 mg/kg) divided 2-3 times per day for 3-10 days (mean 5.7 days) intravenously. The overall efficacy rate was 96.6%. As to adverse reaction, drug fever was observed in 1 patient. Abnormal laboratory data were noted in 4 cases (elevation of serum GOT, GPT and BUN in 1, elevation of serum GOT and GPT in 1, elevation of BUN in 1 and leukopenia in 1).

Retarded mesangial transport and its pathomorphologic sequelae in human and experimental renal diseases.

Human renal biopsy specimens (472 cases) from varied kidney diseases, especially minimal glomerular change group and other idiopathic glomerular diseases having nephrotic manifestation of mainly juvenile individuals, showed morphologic evidence of paraarterial deposits of afferent arterioles at the glomerular entrances in more than 50% of examined cases. Because these deposits were often accompanied with concomitant mesangial, intraarterial and subendothelial deposits of afferent arterioles, it was felt that retarded mesangial transport which is ordinarily associated with certain glomerular diseases might be an important factor to produce these particular paraarterial deposits. The referred deposits of minimal glomerular change group cases were thought to predispose the occurrence of focal sclerotic capillary lesions at the vascular poles of glomeruli. The experimental chronic nephrotic rats produced by daily administration of aminonucleoside of puromycin revealed mesangial dysfunction with increased uptake and retarded disposal of secondarily overloaded aggregated human gamma globulin at mesangial areas in glomeruli. Besides, the increased deposits of autologous serum proteins in mesangial areas and arteriolar walls were common findings in those rats, and these deposits were observed to be always preceded to the occurrence of segmental sclerotic changes of glomeruli, which were often associated in the later stage of this experiment.