Does status epilepticus in children cause developmental deterioration and exacerbation of epilepsy?

The aims of this study were to determine predictors of abnormal outcome, neurodevelopmental deterioration, new-onset epilepsy, refractory epilepsy, and recurrent status epilepticus in children presenting with status epilepticus. For all children presenting to Royal University Hospital, Saskatoon, Saskatchewan, Canada, with status epilepticus between January 1987 and December 1996, demographic data, details of status epilepticus (etiology, duration, treatment, and investigations), developmental milestones, seizures prior to and following status epilepticus, recurrent status epilepticus, and neurologic examination findings at status epilepticus and at follow-up were collected by chart review, patient interview, and neurologic examination. Neurodevelopmental outcome was determined for all subjects except those who died during the initial hospitalization. Predictors of new-onset epilepsy, refractory epilepsy, and recurrent status epilepticus were determined for children followed for 3 months or more after status epilepticus. At follow-up, 79% were abnormal neurologically. Predictors included etiology (nonfebrile or nonidiopathic), perinatal difficulties, preceding developmental delay, abnormal initial neurologic examination; and abnormal neuroimaging. Thirty-four percent showed neurodevelopmental deterioration; predictors included etiology (nonidiopathic or nonfebrile), young age at status epilepticus (12 months or less), and abnormal neuroimaging. Thirty-six percent with no history of seizures preceding status epilepticus developed epilepsy and 25% developed refractory epilepsy. Fifty percent of children had recurrent status epilepticus. In conclusion, very few children presenting in status epilepticus were normal at follow-up. Sequelae were seen predominantly in those with a nonidiopathic, nonfebrile etiology, whereas those with idiopathic or febrile status epilepticus did well.     

2-5A-DNA conjugate inhibition of respiratory syncytial virus replication: effects of oligonucleotide structure modifications and RNA target site selection.

To define more fully the conditions for 2-5A-antisense inhibition of respiratory syncytial virus (RSV), relationships between 2-5A antisense oligonucleotide structure and the choice of RNA target sites to inhibition of RSV replication have been explored. The lead 2-5A-antisense chimera for this study was the previously reported NIH8281 that targets the RSV M2 RNA. We have confirmed and extended the earlier study by showing that NIH8281 inhibited RSV strain A2 replication in a variety of antiviral assays, including virus yield reduction assays performed in monkey (EC90 = 0.02 microM) and human cells (EC90 = microM). This 2-5A-antisense chimera also inhibited other A strains, B strains and bovine RSV in cytopathic effect inhibition and Neutral Red Assays (EC50 values = 0.1-1.6 microM). The 2'-O-methylation modification of NIH8281 to increase affinity for the complementary RNA and provide nuclease resistance, the introduction of phosphothioate groups in the antisense backbone to enhance resistance to exo- and endonucleases, and the addition of cholesterol to the 3'-terminus of the antisense oligonucleotide to increase cellular uptake, all resulted in loss of activity. Of the antisense chimeras targeting other RSV mRNAs (NS1, NS2, P, M. G, F, and L), only those complementary to L mRNA were inhibitory. These results suggest that lower abundance mRNAs may be the best targets for 2-5A-antisense; moreover, the active 2-5A antisense chimeras in this study may serve as useful guides for the development of compounds with improved stability, uptake and anti-RSV activity.     

Astrocytic differentiation in medulloblastoma.

A case of cerebellar medulloblastoma with transitional features towards malignant fibrillary astrocytoma is described. In the cerebellum the tumour is characterised by extensive subpial infiltration with cells of undifferentiated type, and the astrocytic component could only be identified by a positive glial fibrillary acidic protein reaction. In the brainstem the character of the growth transforms to that of diffuse astrocytoma. This demonstrates the potential for differentiation existing in a "primitive" neuroepithelial neoplasm.     

A pilot study of cyclical chemotherapy with high-dose methotrexate and CHOP (MTX-CHOP) in poor-prognosis non-Hodgkin's lymphoma (NHL)

Summary In a pilot study of cyclical chemotherapy in patients with poor-prognosis non-Hodgkin's lymphoma (NHL), high-dose methotrexate (MTX) 1 g/m² with folinic acid rescue was given as initial treatment and then between cycles of a single-arm CHOP combination administered every 4 weeks. Of 21 patients with previously untreated or minimally treated grade 2 (high-grade) histology stage II/III/IV NHL, 13 (62%) achieved complete remission (CR); the CR rate for stage III/IV patients was 56%. Of all 25 patients with grade 2 stage II/III/IV NHL, including previously treated patients, 16 (64%) achieved CR. The median folow-up of patients who completed treatment is currently 22 months and only 1 relapse has been recorded in the CR group. Only five of 24 grade 2 patients given the initial test MTX failed to show any response, and eight patients achieved partial remission (PR) as a result of this single treatment. The response to MTX-CHOP in nine patients with grade 1 (low-grade) histology NHL was poor; only two achieved CR. These findings lend support to other data which indicate a useful role for MTX in the induction chemotherapy of advanced high-grade NHL, though the optimum dosage and drug sequence have yet to be determined.for the Yorkshire Lymphoma Group (YLG)     

Hypospadias trends in two US surveillance systems

OBJECTIVE: Hypospadias is a common congenital anomaly, the cause of which is unknown. Unexplained increases in the rates of hypospadias occurred in five European countries in the 1970s and 1980s. We examined data from two birth defects surveillance systems in the United States for evidence of similar trends. METHODOLOGY: The Metropolitan Atlanta Congenital Defects Program (MACDP) provided birth prevalence rates from 1968 to 1993. The nationwide Birth Defects Monitoring Program (BDMP) provided rates from 1970 to 1993. MACDP data are population-based and could be categorized by the severity of the hypospadias. BDMP data allowed analysis of rate trends for the four census regions of the United States. RESULTS: Data from both surveillance systems showed an approximate doubling of hypospadias rates in the 1970s and 1980s. MACDP data showed that the rate of severe cases increased while the ratio of mild to severe cases decreased. BDMP data showed that hypospadias rates increased markedly in all four regions of the United States. CONCLUSIONS: The observed increases are unlikely to be attributable to increased sensitivity of the surveillance systems or the identification of more mild cases by physicians over time, because either trend would have increased rather than decreased the ratio of mild to severe cases. If real, these trends represent the largest number of cases and the first report of an increase in hypospadias rates outside of Europe. Additional investigation of a possible increase in hypospadias rates is warranted.     

Medicine inspired by poverty

Since his arrival in Egypt in 1994 the author joined a number of archaeological expeditions as a surveyor and part-time physician. During this latter activity he came into contact with the beliefs and practices of the local workmen and those of the Ababda Bedouin in particular. Living a harsh life in the southern part of the Egyptian Eastern Desert, their medicine seems to be inspired by poverty. Widely used for all internal disorders are 'kaya bil-naar': oval scars made with red-hot metal instruments. Another, less common, form of scarification is 'mi'ah-hed'asher', three parallel lines carved deeply into the cheek of the patient. 'Muhawy' is the bite of a snake into the earlobe of the patient, to prevent snake-bites. Another prophylactic is the 'higab', a small leather pouch containing a magical object or text. Therapies for less serious disorders include the use of herbs, spices and foodstuffs, often prepared in special ways. Externally, car fuel and axle grease are widely used. With the development of the Red Sea coast for tourism, the life of the Ababda Bedouin will change fundamentally. The above practices are likely to be replaced by Western medicine, probably a change for the better for these people.     

Value of a Dutch medical license in Egypt

Shortly after moving from the Netherlands to Egypt, the author, a physician, started procedures to get his medical certificate recognized. These procedures began at the Egyptian Medical Association, housed in the Dar al-Hikmah ('House of Wisdom'). The Association first required a comparison between the Netherlands and the Egyptian medical education, to be made by the Supreme Council of Universities. There, the differences between the two systems appeared to be fertile soil for confusion and discussions. After nine months, however, and the translation of all relevant papers into Arabic, the Supreme Council declared the Dutch medical education equivalent to the Egyptian. Now only the permission of the Ministry of Health and Population was required. This Ministry inquired at the Ministry of Foreign Affairs whether an Egyptian education would be recognized in the Netherlands, in order for the 'principle of reciprocity' to be applied. The reply of the Dutch Embassy was positive but progress has stopped since. A registration as a physician in the United Kingdom was obtained without problems and in a short time; this registration might be helpful in efforts to resume the process in Egypt.