High response rate to cisplatin/etoposide regimen in childhood low-grade glioma.

PURPOSE: The aim of this study was to avoid radiotherapy and to induce an objective response in children with low-grade glioma (LGG) using a simple chemotherapy regimen based on cisplatin and etoposide. PATIENTS AND METHODS: Thirty-four children (median age, 45 months) with unresectable LGG were treated with 10 monthly cycles of cisplatin (30 mg/m(2)/d on days 1 to 3) and etoposide (150 mg/m(2)/d on days 1 to 3). Tumor originated in the visual pathway in 29 patients, in the temporal lobe in two, in the frontal lobe in two, and in the spine in one. Eight children were affected by neurofibromatosis type 1. Objective tumor response and toxicity were evaluated by magnetic resonance imaging and neurologic and functional tests at 3-month intervals. RESULTS: An objective response was obtained in 24 (70%) of 34 patients, whereas the others had stable disease. None of the children were electively irradiated. In 31 previously untreated children, overall survival was 100% and progression-free survival was 78% at 3 years, with a median follow-up of 44 months. Acute toxicity was unremarkable; 28% patients evaluated for acoustic neurotoxicity revealed a loss of perception of high frequencies. CONCLUSION: Cisplatin and etoposide combined treatment is one of the most active regimens for LGG in children and allows avoidance of radiotherapy in the vast majority of patients.     

Increased CA 125 serum levels in patients with advanced acute leukemia with serosal involvement

BACKGROUND: CA 125 is a tumor marker used for the diagnosis and monitoring of ovarian carcinoma. This marker also has been found to be increased in patients with serosal effusion derived from nonneoplastic inflammatory disease and in a few instances of advanced non-Hodgkin lymphoma with serosal involvement. METHODS: CA 125 levels were tested in the serum of 15 patients with acute myeloblastic leukemia (AML) at the time of diagnosis and in 3 patients with advanced leukemia with serosal involvement. In two patients with elevated serum CA 125 levels, a CA 125 assay was performed on leukemic cells and on the supernatant fluid of short term liquid culture. RESULTS: Increased serum CA 125 was found in the three patients with acute leukemia with extramedullary localization and serosal effusion, whereas it was normal in 15 AML patients tested at the time of diagnosis. CA 125 was not detectable in leukemic cell extracts nor in the supernatant fluid of primary cultures. CONCLUSIONS: These results indicate that leukemic cells were unable to produce CA 125 and suggest that its elevation in the serum is likely due to a serosal inflammatory reaction caused by the leukemic infiltration.     

Neuro-cognitive development and epilepsy outcome in children with surgically treated hemimegalencephaly

We performed a long-term follow-up of 10 patients with hemimegalencephaly and refractory epilepsy, after having treated them with hemispherectomy. Before surgery, 9 patients presented with delayed motor and cognitive development. Surgery was performed between age 5 months and 4 years and 8 months; the mean postsurgical follow-up was 5 years and 2 months. The epilepsy improved in most cases: 6 patients became seizure-free and 2 presented only dystonic fits. The cognitive outcome was less favourable, even though some improvement of cognitive competence was found in all. The neurological deficit did not increase after surgery, and the quality of life improved significantly. A good cognitive development before surgery, less severe morphological changes in neuroimaging, and functional and anatomical integrity of the "healthy" hemisphere seem to be associated with a better cognitive outcome.     

Evaluation of analgesic and anti-inflammatory activity of novel beta-lactam monocyclic compounds

We have examined the in vivo anti-inflammatory and analgesic activity of a new series of monocyclic beta-lactams (azetidinones), similar to others which have been demonstrated to be inhibitors of human leukocyte elastase (HLE), an enzyme involved in degradation processes of connective tissue. Our new compounds have been administered orally (15 mg/kg) to albino rats 30 min before injecting carrageenin in the plantar aponeurosis. Tested compounds have demonstrated a certain activity and stability to gastric hydrolysis, in particular two of them markedly reduced paw edema formation, even if slightly less effectively than indomethacin (reference compound, 5 mg/kg). To evaluate the analgesic activity we carried out the acetic acid writhing test, pretreating rats orally with our compounds 30 min before injecting the acid solution i.p. The same two molecules which showed the anti-inflammatory activity demonstrated a very light analgesic activity. These results suggest the possibility of carrying out further studies, particularly in vitro, on the mechanism of action of our compounds, mechanism which could be the HLE inhibition.     

Myoclonic epilepsy with photosensitivity in infants with Pallister-Killian Syndrome

IntroductionPallister-Killian Syndrome (PKS) (OMIM #601803) is a rare genetic disorder caused by a mosaic tetrasomy of the short arm of chromosome 12. Epilepsy is a frequent concern in PKS patients.Methodswe report 3 PKS patients, with early-onset myoclonic epilepsy and photosensitivity. In these children, we analysed epileptic history and the EEG phenotype.ResultsEpilepsy onset was in the first 2 years of life in all patients and in 2 of them myoclonic seizures were the only seizure type. In all children photosensitivity was observed and myoclonic seizures were mainly related to low-frequency (1–6 Hz) intermittent photic stimulation. Levetiracetam was effective and well tolerated in the 2 treated patients.Conclusionsearly-onset myoclonic epilepsy is a possible clinical manifestation of PKS. Low-frequency photosensitivity is a peculiar bioelectrical marker in these children.     

Angiotensin-converting enzyme inhibitor use in older patients with heart failure and renal dysfunction

OBJECTIVE: To examine the relationship between angiotensin-converting enzyme (ACE) inhibitor use and clinical outcomes among recently hospitalized patients with congestive heart failure (CHF) and coexisting renal insufficiency. DESIGN: A prospective cohort study. SETTING: Ten community hospitals in upstate New York. PARTICIPANTS: A total of 1076 hospital survivors identified from a consecutive series of CHF inpatients. MEASUREMENTS: Patients were followed prospectively for 6 months after hospital discharge to track mortality, hospital readmission, and quality of life. Clinical outcomes were stratified by ACE inhibitor use among those with renal dysfunction, defined as serum creatinine > or = 2.0 mg/dL, and among the remaining patients, whose serum creatinine was < or = 1.9. RESULTS: ACE inhibitor use was lower among 187 patients with renal dysfunction than among 889 patients with preserved function (41 vs 69%, P < .001). Age and sex were among the significant determinants of drug use in both groups. After adjustment for covariables, ACE inhibitor use among those with abnormal renal function was not associated with a lower risk for death or readmission, or better quality of life. By comparison, ACE inhibition conferred meaningful clinical benefit among those whose creatinine was < or = 1.9 mg/dL. CONCLUSION: Convincing evidence of clinical benefit from ACE inhibitor use is not readily detectable among a sample of 187 unselected older patients with CHF and moderate or severe renal insufficiency. Further studies to identify subsets of this group who might benefit are warranted.     

What is the normal aganglionic segment of anorectum in adults?

INTRODUCTION: Ultrashort-segment Hirschsprung's disease as a cause of obstructed defecation is controversial because of a lack of knowledge regarding the normal aganglionic zone of the distal rectum. The intent of this study was to define the normal aganglionic zone of the distal rectum through histologic review of cadaveric dissections. METHODS: Cadavers were obtained from the anatomic pathology laboratory at the University of Massachusetts Medical School. Strip myectomy with overlying mucosa was performed from distal to the dentate line to at least 3 cm into the anal canal and rectum after the pelvis was hemisected. Specimens were fixed in 10 percent buffered formalin. Specimens were sectioned serially every 3 mm and embedded in paraffin. Four-micron slices were then stained with hematoxylin and eosin. Each section was examined by a gastrointestinal pathologist. The presence or absence of nerves and ganglion cells was recorded. RESULTS: Thiry cadavers were obtained for analysis. Mean age at time of death was 79 (range, 65-97) years. There were 13 men. The mean distance of aganglionic bowel from the dentate line was 6.6 (range, 0-21) mm in Meissner's plexus and 5.1 (range, 0-15) mm in Auerbach's plexus. CONCLUSION: The normal distance of aganglionic bowel wall is 2 cm or less from the dentate line. The absence of ganglion cells proximal to this normal aganglionic zone in the patient with clinical findings of lifelong obstructed defecation defines ultrashort-segment Hirschsprung's disease.