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Biomedical subjects

G Jacobi

Publications and source records attributed to G Jacobi.

At least 19 recordsLinked to original sources

Desmoplastic supratentorial neuroepithelial tumours of infancy.

The clinicopathological features of two infants with desmoplastic supratentorial neuroepithelial tumours are described. The cases were similar to the 26 cases reported previously as desmoplastic infantile ganglioglioma and superficial cerebral astrocytoma attached to dura. Neuronal differentiation was absent on routine stains, but was immunohistochemically established. We review the literature and suggest classifying this clinicopathological entity by using a general designation such as desmoplastic supratentorial neuroepithelial tumours of infancy, a term which indicates the variability in the amount and lines of differentiation.

Astrocytoma

EEG and evoked potentials in HIV-infected children.

Forty-seven HIV-seropositive children were investigated by EEG and evoked potentials (BAEP, SEP). Twenty-three children were symptomatic (P2), 8 seropositive without symptoms (P1), and 16 children were less than 15 months of age (P0). Some of them were investigated at different stages of HIV infection. During the neonatal period, 7 newborns of drug-addicted mothers had seizures and frequent spikes and sharp waves in their EEGs. Among (P2) children 6/23 showed background slowing and 1 had rhythmic theta activity (6 with and 1 without neurological symptoms). In BAEP, bilateral prolonged interpeak latencies (IPL) were found in 1 child with severe AIDS encephalopathy. Side differences greater than or equal to 0.4 ms in IPL were seen in 2 (P2), 1 without and 1 with neurological symptoms. A late onset was seen in 2 (P1) and 4 (P2) children. Median SEPs were normal in 24/26 patients; N20/N13 amplitude ratio was reduced in 2 (P1) patients. EEG and BAEP revealed nonspecific abnormal features in HIV encephalopathy. The the progression of the disease. However, also in the symptomatic group, normal results of EEG and BAEP dominated. SEP in the symptomatic group revealed only normal values. For monitoring the effectiveness of AZT treatment in HIV encephalopathy, EEG seems to be a relevant investigation; for evoked potentials more data and experience are needed.

AIDS Dementia Complex

Immunocytochemical characterization of cytomegalovirus (CMV) infected giant cells in perinatal acquired human immunodeficiency virus (HIV) infection.

In a pediatric case of necrotizing CMV myelitis after perinatal HIV infection characteristic cytomegalic cells, which could not be attached to a particular cell line by cell morphology, were studied after immunostaining with monoclonal and polyclonal antibodies raised against GFAP, S100 protein, NSE, synaptophysin, factor VIII, vimentin, macrophages, leukocytes, CMV, HSV I + II, toxoplasma, and HIV 1 gp41. Astrocytes, oligodendrocytes, neurons, ependymal and endothelial cells, macrophages, and Schwann cells stained positively with CMV antiserum. With regard to their immunological features the majority of cytomegalic cells ("owl eye cells") was identified as astrocytes, and in decreasing frequency, the remainder was characterized as macrophages, mesenchymal, and endothelial cells. It is concluded that CMV giant cells represent one phase of virus induced cell transformation, not only one single, but numerous cell types are exposed to after CMV infection.

Acquired Immunodeficiency Syndrome

Rapid development of giant aneurysm at the base of the brain in an 8-year-old boy with perinatal HIV infection.

An 8-year-old boy with perinatal HIV infection developed a large fusiform aneurysm in the circle of Willis two years prior to death which was confirmed by radiological studies. The postmortem examinations revealed a predominantly intimal, proliferative lesion, and partial destruction of the internal elastic lamina in the involved arteries. Within the intima hyperplasia of fibroblasts and smooth muscle cells was observed. No inflammatory alterations, no granulomas and no multinucleated giant cells could be noted in the vascular walls and in the cerebral parenchyma. A small ischemic infarct was present in the left thalamus. Cerebellum, brainstem and medulla showed multiple areas of progressive multifocal leukoencephalopathy (PML). Immunohistochemistry with anti-gp41, a monoclonal antibody against HIV envelope did not exhibit any positive results. These findings implicate that the vascular lesion might be attributed to primary infection of the brain by HIV which led to a defect of elastic lamina and consecutive intimal hyperplasia. A second hypothesis could be based on the effect of extremely high dose AZT therapy avoiding inflammatory reaction after HIV infection.

Acquired Immunodeficiency Syndrome

[Post-traumatic epilepsy].

There might be 3 different forms of epilepsy following head injury: earliest seizures with occasional characteristics, early seizures prompting considerations of differential diagnosis, and, late seizures which might have a chronic course = posttraumatic epilepsy proper. The risks to have posttraumatic epilepsy for a child suffering from head injury are: penetrating cranial trauma, early seizures, intracranial hemorrhage, unconsciousness > 24 hours, depressed fracture with dural laceration and unconsciousness > 24 hours, fractures on the base of the skull, focal synchronous activity in the EEG which is related to the site of brain injury. If a or > or = 2 of b-g are given we recommend prophylactic antiepileptic therapy: in the younger (< 5 years) with a low dose of phenobarbital and in the elder (> 5 years) carbamazepine for at least 2 years of treatment.

Brain Injuries

[Physiologic blood coagulation studies in idiopathic arterial thrombosis].

QUESTIONING: The prevalence of inherited thrombotic syndromes in the general population appears to be higher than that of inherited bleeding disorders. However, the most important candidates for screening are patients with unexplained thromboembolism at ages of less than 40 years: In 19 children suffering from "idiopathic" arterial thrombosis laboratory screening has been performed. METHODS: PT, PTT, TT, platelet count, spontaneous platelet aggregation, von Willebrand-factor, fibrinogen, plasminogen, antithrombin III, protein C, C1-inactivator, alpha-1-antitrypsin, alpha-1-antichymotrypsin, alpha-2-antiplasmin and alpha-2-macroglobulin have been investigated. RESULTS: Compared to an age matched healthy control group we could demonstrate in children with arterial thrombosis in vitro platelet activation with significant enhanced platelet aggregation, elevated levels of von Willebrand-factor and alpha-1-antichymotrypsin at the onset of disease. Protein C and alpha-2-antiplasmin were significantly decreased. These changes turned back to normal in the following 6 to 9 months. PT, PTT, TT, platelet count, plasminogen, alpha-1-antitrypsin, c1-inactivator and alpha-2-macroglobulin showed no alterations compared to controls. CONCLUSIONS: Platelet activation and alteration of platelet function have been shown in vivo and in vitro to initiate thrombosis. The von Willebrand's VIII molecule is involved in this step. The lowering of protein C levels at the onset of thrombotic diseases is discussed to be due to an increased turnover, whereas the decreased levels of alpha-2-antiplasmin might be a counter-regulation to the thrombotic event, showing an "activated" fibrinolytic system.

Adolescent

Central nervous system involvement of children with HIV infection.

The neurological findings in 41 HIV-seropositive children are described. 23 children were symptomatic, eight seropositive but without symptoms and 10 seropositive children less than 15 months of age had no other evidence of immunodeficiency. Acquired microcephaly, developmental regression and progressive motor deterioration indicated HIV encephalopathy, as did developmental delay, mental retardation, cerebellar symptoms and behavioural changes. Three children with progressive encephalopathy improved after treatment with azidothymidine (AZT). In eight children treated with prophylactic intravenous immunoglobulin therapy (IVIG) and seven treated with both IVIG and AZT, no mental deterioration has been observed since the beginning of therapy. One child with advanced encephalopathy and severe pyramidal tract involvement did not improve.

Adolescent

Expression of the HSV-2 ribonucleotide reductase subunits in adenovirus vectors or stably transformed cells: restoration of enzymatic activity by reassociation of enzyme subunits in the absence of other HSV proteins.

We have cloned the large subunit (RR1) of the HSV-2 ribonucleotide reductase into a helper-independent adenovirus 5 vector under control of the viral major late promoter. Infection of 293 cells with the AdRed-1 recombinant virus resulted in the expression of the HSV-2 RR1 protein. We have also produced cells which constitutively express the small (RR2) subunit of the HSV-2 enzyme by transfecting 293 cells with a plasmid encoding this protein and the neo resistance marker (pSV2neo-RR2). Infection of the A439-14 producer cells with AdRed-1 resulted in the expression of enzymatically active HSV-2 ribonucleotide reductase. HSV-2 reductase activity could also be detected upon mixing of extracts from cells expressing either subunit. Our results indicate that the HSV-2 holoenzyme can be reconstituted in vivo and in vitro and that no HSV-2 proteins, beyond the enzyme subunits, are required for the formation and activity of the viral reductase.

Adenoviridae

[Van der Woude syndrome in combination with ring chromosome 18].

7-month-old girl with a combination of van der Woude syndrome and ring chromosome 18 showed the following malformations: medial palate cleft, fistulas of the lower lips, hypertelorism, epicanthus, antimongoloid position of the eyelids, a small hymenal appendix, plantar placing of the third toe, atrial septum defect, stenosis of the auditory canal. The combination of fistulas of the lower lip and cleft lip or palate already established the diagnosis of Van der Woude Syndrome. Because of the additional malformations observed a chromosome analysis was performed which demonstrated a ring chromosome 18. The phenotypic features of ring-chromosome 18, a 18p-/18q- syndrome, vary according to the extend of deletion of the short or long arm. However, all patients show craniofacial dysmorphism, intellectual and developmental retardation, defective hearing, speech disorder, and more than 50% have stenosis or atresia of the auditory canal.

Abnormalities, Multiple

[Double urologic tumors: reduced immunocompetence?].

55 patients with primary multiple neoplasias underwent immunostaging with determination of the immunoglobulins, B- and T-lymphocyte counting, H3-lymphocyte stimulation (ConA, PWM, PHA) and DNCB-epidermal test. There were no significant differences between the PMN-group and a group of patients with solitary tumors, whereas both cancer patient groups revealed a diminished immunocompetence compared with a non-malignant control group of patients.

Adult

[Microrheological studies in healthy subjects. Effect of cigarette smoke and oral contraceptives on erythrocyte flexibility].

Erythrocyte flexibility was tested in 29 healthy subjects, using whole-blood filtration through membrane filters with 5 micron pores, special attention being given to cigarette smoking and oral contraceptives as risk factors. Red cell flexibility was significantly reduced in male smokers compared with non-smokers (P is less than 0.0001), and in all male and female smokers (P is less than 0.05) An influence of oral contraceptives to erythrocyte flexibility could not be found. Reduced erythrocyte flexibility in smokers as a factor contributing to an abnormal microcirculation and to the development of arterial occlusive disease is discussed.

Adolescent

[High dosage methotrexate in combination with "8 in 1" in therapy of pediatric grade III/IV brain tumors].

20 patients with malignant brain tumors in childhood were treated according to a regimen which included initial surgery, preradiation chemotherapy and subsequent irradiation. The chemotherapy consisted of alternating cycles of high-dose methotrexate (12 g/m2) and "8 drugs in 1 day" (Bleyer, 1983). Each cycle was to be given up to six times, as tolerated. The diagnoses were medulloblastoma in 10 cases, astrocytoma in 5 cases, ependymoma and PNET in 2 patients each, and malignant mesenchymoma in 1 case. 15 patients were previously untreated, 5 patients experienced relapse after a different first line therapy and a longer time interval. 8 patients are in continuous complete remission for 13 to 54 months. The toxicity upon the bone marrow, the kidney and the inner ear was tolerable. Long lasting emesis contributed a marked problem to the patients but did not cause abbreviation of the therapy. The neurotoxicity was notably mild. Three episodes of generalized seizures were seen without subsequent sequelae, four cases of peripheral neuropathy were attributable to vincristine. A leukoencephalopathy was neither detected on clinical grounds nor on neuroradiological imaging. Therapy related deaths were not seen. We conclude that the combination of HD-MTX and "8 in 1" markedly contributes to the intensification of the chemotherapy for malignant brain tumors in childhood. In the setting as preradiation chemotherapy the toxicity is tolerable.

Adolescent

[Clinical picture and pathophysiology of elevated intracranial pressure].

In 48 children who had raised intracranial pressure (icp) this was monitored continuously by an epidural route. Icp-values were correlated with other important parameters like the mean arterial pressure (map) and the early components of brainstem acoustic evoked responses (BAER). The results were as follows: 1. focal and multifocal brain lesions resulting in vasogenic brain edema have better prognosis than those morbid conditions causing cytotoxic edema. In the letter group the whole brain's metabolism is impaired, brainstem, cerebellum and spinal cord included. 2. by monitoring map and icp we are enabled to assess the cerebral perfusion pressure. If this value falls short of 20 Torr the duration of unconsciousness and the frequency of brainstem related symptoms increases as well as impairment of cranial nerves and cerebellar-extrapyramidal symptoms and mental handicaps in the long term course. 3. cerebral dysfunction and organic brain syndromes in general are not related to icp-increase. They resemble local brain damage, e.g. after contusions. 4. serial registration of BAER is a good aid in iatrogenic induced deep phenobarbital coma. If there are critical values of the perfusion pressure mainly the waves III and V of BAER have increased peak latencies and go flattened. This trend takes place slowly within hours or even days. Loss of the components III and V is prompted by an irreversible damage of the caudal brainstem. This finding after cytotoxic brain edema is even more relevant than after vasogenic edema. If the component loss III-V is bilateral dissociated brain death has to be anticipated. Some important issues of icp-pathophysiology are discussed according to the literature.

Brain Injuries