Pyridoxal 5'-phosphate may be curative in early-onset epileptic encephalopathy.

Neonatal epileptic encephalopathy can be caused by inborn errors of metabolism. These conditions are often unresponsive to treatment with conventional antiepileptic drugs. Six children with pyridox(am)ine-5'-phosphate oxidase (PNPO) deficiency presented with neonatal epileptic encephalopathy. Two were treated with pyridoxal 5'-phosphate (PLP) within the first month of life and showed normal development or moderate psychomotor retardation thereafter. Four children with late or no treatment died or showed severe mental handicap. All of the children showed atypical biochemical findings. Prompt treatment with PLP in all neonates and infants with epileptic encephalopathy should become mandatory, permitting normal development in at least some of those affected with PNPO deficiency.

A novel splice site mutation in the TRIM37 gene causes mulibrey nanism in a Turkish family with phenotypic heterogeneity.

Mulibrey nanism (muscle-liver-brain-eye nanism; MUL) is an autosomal recessively transmitted disease characterized by severe growth delays of prenatal onset caused by mutations in the TRIM37 gene. Recent studies on the subcellular localization revealed that the TRIM37 (KIAA0898) protein is located in peroxisomes. Therefore, MUL has been classified as a new peroxisomal disorder. Up to now, four mutations have been reported, all of which lead to frameshifts and truncated proteins. In this study, mutation screening was performed for the coding region of the TRIM37 gene in a Turkish family by means of RT-PCR and direct cDNA sequencing. We have identified a novel mutation resulting in a frameshift cosegregating within the family. Finally, we report on the presence of novel splice variants observed in lymphoblastoid cells and muscle tissue of normal subjects and patients.

Carboplatin and radiotherapy in the treatment of head and neck cancer: six years' experience.

Between 1987 and 1991, 103 patients with advanced head and neck carcinoma were treated with radiochemotherapy plus carboplatin. Tumors were located in the oral cavity in 33 patients, the oropharynx in eight, and the hypopharynx in seven. Four patients had a tumor of the epipharynx and three, tumor of the larynx. In 48 patients tumor involvement included two or more compartments. Radiotherapy was performed with cobalt-60 rays or 8-MeV photons in a fractionation of 5 x 2 Gy/wk to a dose of 50 Gy. Carboplatin 60 to 70 mg/m2/d was administered days 1 through 5 and 29 through 33. For inoperable patients radiotherapy was continued to a dose of 70 to 74 Gy. To date, 103 patients have entered the study and 100 have completed treatment; three patients died during the treatment period. Actuarial 1- and 2-year survival rates are 77% and 53%, respectively, for all patients; comparable figures for patients with interposed surgery are 93% and 69%, and for the patients treated with radiotherapy alone, 71% and 47%. In a pilot study conducted between 1990 and 1991, 15 patients with advanced head and neck carcinomas underwent hyperfractionated accelerated radiotherapy (2 x 1.6 Gy/d 5 days per week; total dose, 64 to 67.2 Gy) and simultaneous intravenous carboplatin (60 mg/m2, days 1 through 5 and 29 through 33). Eleven patients had T4 and four had T3 tumors. At the end of the treatment period, 12 patients had achieved a complete tumor remission and all others attained a partial tumor involution. Although acute side effects were more pronounced compared with conventional irradiation, this treatment regimen is feasible and the initial complete remission rate of 80% is encouraging. As a result of the encouraging results achieved with hyperfractionated accelerated radiotherapy, we initiated a multicenter randomized study in November 1991. Patients with advanced head and neck carcinomas are either randomized for conventional radiotherapy plus carboplatin or hyperfractionated accelerated irradiation plus carboplatin. As of July 1994, 178 patients have been entered in the study. Results will be evaluated after the study is completed.

[Radiosensitivity of hyperpentaploid cell clones in vulvar neoplasms]. / Radiosensitivität hyperpentaploider Zellklone bei Vulvakarzinom.

INTRODUCTION: Intension of our examination is to investigate changes in ploidy during radiotherapy and to find out radiosensitive cloni of tumors. PATIENT AND METHODS: In November 1993 a 83-year old patient with a carcinoma of the vulva was introduced to the Strahlenklinik der Städtischen Kliniken Offenbach. It was a stage T3N0M0 tumor (UICC 1990). We performed daily smears of the tumor surface during radiotherapy. The smears became air-dried before fixation in PBS/formaldehyde and staining with the Feulgen procedure. The DNA-analyse took place at an image-analysis-system (Ahrens Cytometry Analyse System). RESULTS: Nine and 16 weeks after radiotherapy the patient showed clinically complete remission. Macroscopically and histopathologically there was no tumor found. The ploidy-analysis shows the take off of the hyperpentaploid cells on radiotherapy. Nine and 16 weeks after finished therapy there are no more hyperpentaploid cells detectable. CONCLUSIONS: The DNA-determination is a senseful completition to estimate the success of therapy. It is possible to earn informations about the behaviour of different tumor cell populations during the course of radiotherapy. The hyperpentaploid cells are a radiosensitive part of the tumor. For being able to judge about the route of this cells, if they are proliferating cells of a peritriploid tumor population, or if they proliferate themselves, are some more examinations and additional investigations necessary.

Phase I study of hyperfractionated accelerated radiation and simultaneous Carboplatin therapy for advanced head and neck carcinomas.

From 1990 to 1991 15 patients with advanced head and neck carcinomas underwent hyperfractionated accelerated radiotherapy (2 x 1.6 Gy/day, five days/week, total dose 64.0 to 67.2 Gy) and simultaneous intravenous application of Carboplatin (60 mg/m2, days 1 to 5 and 29 to 33) in a pilot study. Eleven patients had T4 and four had T3 tumours. At the end of treatment twelve patients had a complete tumour remission and in the others a partial tumour involution was seen. Although acute side-effects were more pronounced compared to conventional irradiation this treatment regimen is feasible and the initial complete remission rate of 80% is encouraging.

Chorea Huntington: a rare case with childhood onset.

Chorea Huntington (CH) is a dominantly inherited, neurodegenerative disease usually with adult onset. The course of CH is characterized by movement disturbances, psychiatric symptoms and it may lead to dementia. Typically death occurs after 10 to 20 years of CH duration. Invariably, the underlying mutation concerns an expansion of a polymorphic (CAG) n stretch in the huntingtin gene. Statistically, larger expansions lead to earlier onset of the disease. We report on a girl with a huntingtin allele of > 140 (CAG) n repeats. Unspecific neurological symptoms were noted at the age of 4.3 years followed by rapid disease progression with psychomotor deterioration.