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Biomedical subjects

F Hanefeld

Publications and source records attributed to F Hanefeld.

At least 163 records · Page 9Linked to original sources

[Effect of hyperbilirubinaemia on cerebellar development in Gunn rats].

The influence of bilirubin on cerebellar growth was studied in homozygous Gunn rats by measuring weight, DNA concentration and histochemical enzyme reactions at different ages and under different conditions. High bilirubin levels cause persistent reduction in cerebellar size and loss of Purkinje and granular cells. Sulfonamide application results in an almost complete cessation of cerebellar growth. Phototherapy can prevent these neurotoxic effects of bilirubin. The vulnerability of the cerebellum is particularly high during the period of rapid growth.

Animals↗

Advantages of bicarbonate hemodialysis.

Six patients with frequent episodes of symptomatic hypotension during acetate dialysis were treated with bicarbonate dialysis. In all patients blood pressure, heart rate, and arterial acid-base values were measured every 30 minutes during each of the five treatments with acetate dialysis and bicarbonate dialysis. Hemodynamic parameters were measured invasively in all patients during bicarbonate dialysis and in three of them also during acetate dialysis. Additionally, continuous long-time monitoring with electroencephalography was performed during acetate dialysis and bicarbonate dialysis. During acetate dialysis the patients showed a frequent onset of sudden hypotension and arrhythmia with concomitant symptoms of the so-called disequilibrium syndrome, whereas these symptoms were nonexistent in the same patients during bicarbonate dialysis.

Acetates↗

[Long-term sequelae of neonatal group B streptococcal septicemia/meningitis (author's transl)].

In recent years group B streptococci accounted for nearly 40% of all cases of neonatal septicemia in our intensive-care-unit. Nineteen of 38 babies did not survive the acute illness (mortality 50%). Six of 18 surviving children showed abnormalities related to the septicemia/meningitis (morbidity 33%). The severity of chronic complications ranged from minor neurological problems to marked retardation, deafness, blindness, and epilepsy. In our series there seemed to be a relation between the severity of complications during the acute illness (meningitis, convulsions), and later neurological sequelae. Early detection and early treatment were found to be most important for the final outcome.

Adolescent↗

Occurrence of oligoclonal gammaglobulin in the CSF of children with prolonged and chronic CNS-infections.

CSF-proteins of 1770 children and adolescents with different neurological diseases and of 75 controls were examined by zone electrophoresis in agarose gel electrophoresis and by immunofixation electrophoresis. The quantitative evaluation of the phoretograms by an analog computer revealed oligoclonal changes of the gamma-globulin profile in 53 patients with subacute or chronic CNS-infections and in 5 children with a medulloblastoma. Seventeen of 37 children with congenital infections had 1--5 oligoclonal gamma-fractions consisting of IgG. Five to seven oligoclonal IgG fractions were detected in each of 16 children with SSPE. All 6 adolescents with multiple sclerosis had 2--5 oligoclonal IgG fractions. One to five oligoclonal gamma-bands occurred transiently in the CSF of 4 children with prolonged meningoencephalitis caused by different viruses, in 3 children with a prolonged non-bacterial meningitis of probable viral origin, in 2 infants with prolonged bacterial meningitis after corticosteroid therapy, and in 1 child with prolonged bacterial meningitis during cytostatic therapy. Four to six oligoclonal gamma-subfractions were found at different times during progressive viral encephalitis that developed during maintenance therapy of acute lymphoblastic leukaemia, and in 2 patients with chronic meningoencephalitis of unknown origin. Since oligoclonal gamma-globulin was detected almost invariably in the CSF of patients with prolonged or chronic neurologic infections, this finding implies persistence of antigens in the CNS and pathologic invasion of lymphocytes with selective proliferation of antigen-stimulated clones.

Adolescent↗

Changes of CSF-protein pattern in children with acute lymphoblastic leukemia during prophylactic CNS therapy (Berlin protocol).

The cerebral spinal fluid (CSF)-protein profiles of ten children with previously untreated acute lymphoblastic leukemia (ALL) were investigated by agarose gel electrophoresis. The profiles were determined at diagnosis and during the fifth to eighth week of treatment when preventive therapy for central nervous system (CNS) leukemia (skull irradiation, intrathecal methotrexate (ithMTX) was administered. The profiles were compared with those obtained from a control group of 67 children and those from 42 patients with acute aseptic meningitis. The data from the latter group demonstrated the CSF-protein pattern of partial blood-CSF barrier (B-CSF-B) breakdown. The children with ALL showed no or only minor signs of a B-CSF-B impairment at diagnosis and after four weeks of systemic treatment. However, CSF changes indicative of a lesion of the B-CSF-B increased in all children continuously during CNS prophylaxis. The protein profile at the end of combined chemotherapy and radiotherapy was very similar to that in patients with acute aseptic meningitis. These observations point to neurotoxic side effects on the CNS barrier system with the combination of cranial radiation and ithMTX. A striking finding was restricted heterogeneity of gamma-globulin, observed in the CSF of nine out of the ten children with ALL before or during treatment. The significance of this abnormality is unknown.

Antineoplastic Agents↗

Therapy of acute lymphoblastic leukaemia in childhood: effects on the nervous system.

A number of neurological disturbances occur during the treatment of childhood malignancies with cytotoxic drugs like vincristine, methotrexate, cytosine-arabinoside, cyclophosphamide, asparaginase and others. Neurological complications range from peripheral neuropathy, myopathy, myelopathy to encephalopathy with methotrexate induced encephalopathy leading to permanent brain damage or death in most cases. Irradiation of the brain can produce transient or permanent brain damage by a direct effect on nervous tissue and by altering the blood brain barrier or the blood circulation. The many conflicting reports concerning the quality of life of long-term survivors of childhood leukaemia do not give sufficient data for final conclusions. The experiences we have encountered over the past ten years seem to confirm the optimistic echo from others. There is, however, an urgent need for a prospective study to answer the all important question: will a child suffering from leukemia emerge physically and mentally unharmed after long and aggressive treatment?

Asparaginase↗

Effects of riboflavin on Gunn rats under phototherapy.

Blue and white phototherapy was given to infant (and weanling) homozygous Gunn rats treated with different doses of riboflavin-5-phosphate (ribofl.5'p.) During the first hours after a flavin-injection, the effect of phototherapy with both types of fluorescent lamps was enhanced. With equal radiant power applied, the steepness of serum bilirubin decline depended on the ribofl.5'p. dose injected. After oral or cutaneous application, no similar effect occurred. After a single flavin dose, the serum bilirubin decline lasted for at least 3 hr. Nevertheless, in long-term studies with repeated injections (100 mg/kg every 48 hr), no protective effect beyond that of phototherapy alone could be ascertained on the Purkinje cells in the cerebella of the rats. In the skin of the animals, fluorescence was macroscopically noticeable after ribofl.5'p. injections. When an effective irradiance of about 3.0 mW/cm2 and a high flavin dose (100-200 mg/kg) was administered, histologic investigations of the skin in the abdominal and back region revealed a reversible inflammatory reaction with edema and morphologic changes in the epidermal cells that culminated 12-24 hr after the injection. After a further increase of the effective irradiance, tremendous vesicles on paws, ears, and tails were observed in most of the animals 24-72 hr after the flavin injections. The content of the blisters was primarily serous, later on, often hemorrhagic. Finally, necrosis developed. Acute toxicity of ribofl.5'p. differed markedly when the infant rats (homozygous jaundiced as well as heterozygous nonjaundiced) were kept in the dark or under intense blue phototherapy. Much higher doses were tolerated in the dark. Moreover, it could be demonstrated that ribofl.5'p. does not influence serum bilirubin of jaundiced Gunn rats kept in complete darkness. That suggests that the drug itself does not compete for albumin binding sites. But certain riboflavin ampules (Beflavin) contain stabilizers that considerably displace bilirubin from albumin bonds. Riboflavin disturbs direct photometric bilirubin measurements, but not the diazo reaction. When bilirubin is to be measured in sera containing riboflavin, lights must be extremely dim. Photodegradation in vitro is highly accelerated by the sensitizer.

Animals↗

Febrile convulsions and blood-cerebrospinal fluid barrier.

Three single CSF proteins with different molecular size (albumin, immunoglobulin G, and alpha2-macroglobulin) were determined by the method of electroimmunoassay in 61 children with febrile convulsions (FC) in order to evaluate the permeability of the blood-CSF barrier (B-CSF-B). Forty-two children with acute extracerebral infection served as controls. In contrast to a group of 22 children who suffered from acute meningoencephalitis or encephalitis, the CSF values of 48 children with FC were within normal limits. Thus even a very mild form of inflammatory encephalopathy-undetectable with conventional CSF investigation-was excluded in the majority of the children with FC. In 11 patients, however, CSF concentrations of albumin and alpha2-macroglobulin were abnormally raised, indicating a B-CSF-B distrubance. Elevated albumin values were found most frequently. In several children with FC lasting more than 20-30 min, B-CSF-B damage was probably caused by prolonged seizure activity since there is a linear correlation between albumin concentration and duration of convulsions. Several other factors known to raise the children's risk of developing epilepsy in later life were associated with the protein pattern of B-CSF-B disturbance in some of the children. In these cases, the cause of abnormal permeability of B-CSF-B is unknown and the condition might have existed prior to the occurrence of seizures.

Albumins↗

Sephadex-gel filtration (SGF) in infant and adult Gunn rats.

SGF was compared in infant and adult homozygous Gunn rats. Without any drug application, the test was negative in the adult animals, whereas a remarkable percentage of positive SGF was obtained in 5-7-day-old rats, especially in those undernourished and/or intensely icteric. Unexpectedly, in infant rats the rate of positive SGF after sulfadimethoxine injection was lower than in the untreated control group. Moreover, in 9-10-day-old animals who had positive SGF before the injection, the test became negative 15-20 min after sulfadimethoxine application in vivo. No convincing explanation could be given, but drug interference with the binding capacities of the Sephadex column could be excluded by appropriate in vitro tests.

Age Factors↗

Oligoclonal gamma-globulin banding of cerebrospinal fluid in patients with subacute sclerosing panencephalitis. Comparison of the electrophoretic pattern with that in multiple sclerosis and congenital infections.

Lumbar cerebrospinal fluid (CSF) of 8 patients with subacute sclerosing panencephalitis (SSPE) was examined by agarose gel electrophoresis. In comparison with normal controls and children with different neurological diseases (including infections, tumours and degenerative diseases) the quantitative evaluation of the pherograms by an analog computer revealed an extreme change of the gamma-globulin profile. All cases showed 6-7 abnormal subfractions consisting of 2-4 tall, markedly protruding spikes and several small intermediate fractions. The oligoclonal gamma-globulin contributed 20.1-42.5% to total protein. This particular gamma-globulin profile seems to be highly indicative of the diagnosis of SSPE. It can be distinguished from the oligoclonal pattern in patients suffering from multiple sclerosis (MS) and congenital infections. The CSF protein profile of 13 patients with MS was different from that in SSPE in that it showed 1-5 monoclonal gamma-fractions in every case with none or only one peak protuding more markedly. The percentage of all subfractions amounted to 4.5-23.8% of total protein. As in MS, the aspect of oligoclonality in 9 children with congenital infections (cytomegalic inclusion body disease, toxoplasmosis and rubella) was quite variable, as again 1-5 abnormal subfractions were detected. Their relative concentrations, on the whole ranging from 0.6-12% of total protein, was considerably lower than in SSPE.

Adolescent↗