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The case of an 11-year-old girl with mediastinal stage III B-E Hodgkin's disease is described. She achieved complete remission with combined chemoradiotherapy according to the Swiss Pediatric Oncology Group-HD Protocol 1985. Six months after all therapy was stopped, a slowly growing retrosternal mass was detected. Computed tomography (CT) and gallium-67 single-photon emission CT (SPECT) could not elucidate the true origin of the tumor, nor did ultrasound-guided transthoracic fine-needle puncture. Open biopsy with histologic examination of the lesion has successfully identified the mass as thymic hyperplasia, a rebound immunologic reaction after chemoradiotherapy that mimicked tumor regrowth.

We describe a patient with congenital afibrinogenemia who showed elevated prothrombin activation fragments (F1 + 2) indicating increased thrombin formation. This finding was unexpected since it has hitherto been thought that patients with congenital hypo- or afibrinogenemia have no evidence of increased utilization or accelerated consumption of coagulation factors. No other possible reasons for the elevation of F 1 + 2 were found. Upon fibrinogen substitution F1 + 2 decreased and were again increasing when fibrinogen concentration in plasma fell to very low levels. These findings raise the question of whether increased thrombin formation should be understood as a compensatory mechanism in congenital afibrinogenemia.

The case of an 8-year-old boy with apparently homozygous Bernard-Soulier syndrome (platelet GP Ib/IX complex deficiency) and a transient idiopathic autoantibody against GP Ib/IX is described. He had been diagnosed with chronic autoimmune thrombocytopenia (due to the detection of antiplatelet autoantibodies) before Bernard-Soulier syndrome was proven. Both parents and his brother displayed intermediate deficiency of GP Ib/IX, thus indicating a heterozygote state for Bernard-Soulier syndrome. Alloimmunization as an explanation for the appearance of GP Ib/IX antiplatelet antibodies in the propositus can be excluded. A so-called pseudo Bernard-Soulier syndrome due to selective antibodies was also excluded. Flow cytometric analysis revealed residual expression of 2% GP Ib and 13% GP IX on the propositus' platelets. It seems that the propositus showed an idiopathic autoantibody against a platelet glycoprotein in which he is genetically deficient (but which is not completely lacking). Thus, in patients with untypical behavior upon therapy of "autoimmune thrombocytopenia", other differential diagnoses should also be considered even if antiplatelet antibodies are detected. In addition, all family members displayed elevated concentrations of antiphospholipid antibodies. These findings raise the question of a genetic predisposition for the development of autoantibodies. Moreover, an F. XII deficiency was found in all family members except the mother.

Of 54 children with acute lymphoblastic leukemia (ALL) and first hematological recurrence observed between 1985 and 1989, 31 relapsed while still on treatment and 23 after cessation of therapy. Of the former, only one survived. Of the latter, 11 children survived after a minimum follow-up of 25 months. During the same period, a first isolated testicular relapse was observed in nine boys, of whom six survived, and an isolated CNS relapse in eight patients, of whom three survived. As a rule, survivors of a bone marrow or testicular relapse were doing well while those surviving a CNS relapse had considerable neuropsychological sequelae. These results, compared with those of two preceding studies, suggest that with intensification of front-line treatments, it becomes more difficult to rescue children who relapse, particularly those with a bone marrow relapse while on therapy.

Among a series of 224 patients with aneurysmal subarachnoid haemorrhage (SAH) admitted over a period of three years, 52 patients were prospectively treated with intrathecal tissue plasminogen activator (rTPA). All of these patients were admitted and operated on within 72 h after SAH. SAH was confirmed by CT scan and the volume of blood accumulated in the basal cisterns was graded according to Fisher's scale. All patients had a SAH according to Fisher's grade III, as a prerequisite for inclusion into the study. In 21 patients additional intraventricular bleeding was detectable on CT scan. The diagnosis of a single intracerebral aneurysm as the bleeding source was established by pan-angiography, which also excluded additional cerebro-vascular malformations. The control group consisted of 68 patients, which were also treated within 72 h after SAH. Age and sex distribution as well as the clinical patterns were comparable to the rTPA group. In all patients the aneurysm was clipped using standard microsurgical techniques. After the aneurysm had been excluded from the parent vessel, 10 mg of rTPA, dissolved in 10 ml of its solution fluid, were slowly instilled into the basal cisterns in the treatment group. In patients with additional severe intraventricular bleeding, 5-10 mg of rTPA were injected into the ventricles via an intraventricular catheter at the end of the operation. Apart from the intrathecal application of the thrombolytic substance, the surgical protocol was identical in the patients of the control group. During the postoperative period, the patients in both groups were examined neurologically and by transcranial Doppler on a daily basis.(ABSTRACT TRUNCATED AT 250 WORDS)

Computed tomographic and surgical findings were compared in 30 patients with traumatic frontobasal cerebrospinal fluid fistula. Radiological signs were extension of fractures of the rhinobasis, localized opacification of paranasal sinuses, and localized intracranial air collections. Exact localization of dural tears was only possible in about half of all patients (16 of 30). In conclusion there must be surgical inspection of all fractures of the skull base, and only isolated injuries could be treated by selective surgery.

We describe the clinical course of a 20-year-old man who suffered generalized convulsive seizures with postictal aphasia and hemiparesis of the right side. Computed tomography (CT) displayed a left postcentral lesion with prominent perifocal edema and only a little contrast medium enhancement. The completely removed tumor proved to be a primary cerebral non-Hodgkin lymphoma consisting of T-cells. Only ten days after the operation the patient once more presented a clinical deterioration. A nuclear magnetic resonance imaging (MRI) displayed an annular structure in the area previously operated upon, suspected to be an abscess. The second operation disclosed a large recurrence of the primary T-cell lymphoma extending diffusely into the white matter. On account of the rapid recurrence, a whole brain irradiation was started twelve days after the second operation. Four cycles of chemotherapy followed. Immunohistochemical studies of the anaplastic large lymphoma cells showed staining with the pan T-cell markers (UCHL1, CD3) and with the CD30 (Ki-1) antibody. The B-cell markers (L26, LN1) were negative. The EMA (epithelial membrane antigen) was only partially expressed. Further investigation excluded the presence of systemic lymphoma manifestation. 24 months after the last operation the patient remained free of symptoms. The last MRI displayed no evidence for the recurrence of a lymphoma. In reference to this unusual clinical course the few previously reported cases of the extremely rare primary cerebral T-cell lymphoma are reviewed.

We report on 146 patients with spontaneous intracerebral hemorrhage treated in the period between 1984 and 1988. The aim of this retrospective study was to point out factors for operative respectively conservative treatment. Looking for etiology, age, unconsciousness, localization and extension of hematoma as well as bleeding into the ventricles our results showed that patients over 70 years of age and/or in coma III and IV (Brussels Coma Scale) have a bad prognosis as well as patients with intraventricular bleeding. Patients seem to benefit from operation if hematoma is located in the hemisphere or cerebellar and the extension ranges from 3 to 5 cm.

In order to better define patients who might benefit from cerebral revascularization surgery, transcranial Doppler sonography was used in more than 480 patients. Thus invasive diagnostic studies could be limited to probable surgical candidates. Transcranial Doppler sonography has proven to be reliable for the study of the degree of efficacy of intracranial collateral pathways in hemodynamic borderline situations. Over the last 4 years, the application of the algorithm presented in this paper resulted in a reduction of the number of candidates for surgical revascularization to 19.

The odontogen brain abscess is a relatively rare, but very serious complication of an infection of the teeth. Frequently the bacteria found by aspiration of the brain abscess are the only indication of a dental focus. The diagnostic problems in confirming a covert dental infection as the cause of the brain abscess are illustrated.

Ten patients with orbital fractures and optic nerve trauma are reported. Fractures of the optic canal could be demonstrated by computed tomography in six cases and fractures of the orbital apex in another three cases. Surgical decompression of the optic canal was performed in seven cases. Computed tomography enhanced decision for surgery in cases of intraorbital haematoma with exophthalmus and narrowing of the canal by bony fragments, especially in those patients presenting with incomplete or progressive visual disturbance.

Transcranial Doppler Sonography (TCD) is a noninvasive simple bedside procedure to control continuously cerebral blood flow velocity in basal brain arteries in comatose patients of an intensive care unit (ICU). This measure can already be performed at ICU, to determine timing of angiography for confirming intracranial circulatory arrest when an organ explantation of patients judged clinically brain-dead is intended. TCD is also carried out to assess cerebral circulation in patients with intracranial hypertension. 64 patients are repeatedly evaluated by TCD and have been continuously monitored for ICP at the same time. According to our results a strong correlation between the flow parameters derived from TCD and the ICP exists when the ICP surpasses the level of 25 mmHg. Furthermore repeated control-TCD-examinations of 150 comatose patients in our ICU have elucidated the significant prognostic value of the pulsatility index representing the cerebrovascular resistance. Thereby important informations concerning further clinical course of patients suffering from intracranial hypertension are available. Additionally a clinical example of complete failure of cerebrovascular autoregulation shortly after hypoxic brain damage is demonstrated.

The cytocentrifugation of the liquor cerebrospinalis provides a useful diagnostic tool to differentiate benign from malign diseases of the central nervous system. The method is illustrated with liquor analyses in the field of pediatric oncology: medulloblastoma, leptomeninx sarcoma, plexuspapilloma, astrocytoma, Abt-Letterer-Siwe, ALL, reticulum cell sarcoma, Ewing sarcoma, retinoblastoma. The speed and ease of the processing, the highest possible cellular yield and the good preservation of the cellular characteristics are great advantages of this new method.

Nine children with histiocytosis X were observed. The course of the disease largely depended upon the degree of dissemination at the time of diagnosis. Bone and skin involvement healed completely with a relatively simple therapy using prednisone in combination either with vincristine or vinblastine. Complete or long lasting partial remissions could be achieved up to involvement of 4 organs. Three patients demonstrating histiocyte infiltrations in 5 organs died. They all were less than 2 years of age. Hyperproliferation of monocytopoiesis was present in all patients manifesting itself by a rise in the fraction of mononuclear phagocytes in bone marrow. This variation was paralleled by monocytosis in the peripheral blood in 5 of 7 cases. Serum muramidase levels were increased in 5 of 6 patients. However, there was no clearcut correlation to the degree of disease dissemination.

Of 45 children with ALL who had a first hematological recurrence between 1981 and 1984, 33 relapsed while still on treatment and 12 after cessation of therapy. Of the former 1 of 16 high risk (initial WBC greater than or equal to 20 x 10(9)/l and/or enlargement of the mediastinum) and 5 of 17 low risk patients (initial WBC less than 20 x 10(9)/l and no enlargement of the mediastinum), of the latter 6 patients survived after a minimum follow-up of 20 months. During the same time period, a first isolated CNS relapse was observed in 24 children of whom 16 survived. These results suggest that at the time of evaluation 1. the prognosis of children with ALL in first hematological relapse during the years 1981-1984 was not significantly different from that of similar children treated earlier; and 2. the prognosis of children with isolated CNS relapse had improved.

Unexpected subarachnoid hemorrhage with a fatal outcome was seen in two patients in intensive care in association with trauma and an intracranial inflammatory abscess. The cause of SAH was disclosed at autopsy: traumatic and bacterial aneurysms of the basilar artery respectively. In the reported cases the symptoms of SAH did not suggest an origin.

24 children with low risk acute lymphoblastic leukemia (ALL) in first relapse were re-treated with an aggressive protocol. Therapy of the first episode had adopted two different but equivalent approaches (SAKK-ALL "low risk" 76 and CALGB protocol 7611). With one exception, relapse occurred in all children before discontinuation of therapy. complete remission was achieved in 20 of the 24 children (83%). Five of 11 children in whom the length of the second remission could be evaluated had, at the time of the cutoff, been in continuous remission for 18 to 40 months. The therapy displayed considerable toxicity. From this study it is concluded that remission is achieved in the majority of children with first relapse of ALL, but that the remission can be maintained beyond 18 months only in a few children.

The survival of 20 children with medulloblastoma who received adjuvant chemotherapy with procarbazine, vincristine and prednisone after resection and craniospinal irradiation is compared with the preliminary results of the Children's Cancer Study Group (CCSG) and the international Society of Pediatric Oncology (SIOP) medulloblastoma studies. Survival with the chemotherapy used in the SPOG study ws not superior to the survival of children who received craniospinal irradiation only.

Inheritance of HLA antigens in 55 families of patients with ALL was analyzed. Significantly increased sharing of DR antigens was observed among the parents of the affected children (p = 0.003). A similar increase was noted in the sharing of HLA-B antigens (p = 0.02). The observed number of DR homozygotes among the patients was twice the expected value in families where the parents shared a B and a DR antigen. Segregation analysis of the shared antigens disclosed significant prevalence of heterozygotes among the healthy siblings, which suggested the occurrence of gametic selection in such families. This study indicates that mating of certain shared alleles of the HLA system (especially of the DR locus) is associated with a risk for the offspring to develop ALL in childhood. Restricted heterogeneity of the parental HLA gene pool favours the expression of linked recessive genes and, presumably, of those involved in susceptibility to ALL.

The prevalence of autoimmune diseases, including systemic lupus erythematosus, is increased in failure of certain host defence mechanisms. Systemic lupus erythematosus, however, has not been recorded as a late complication of the Staphylococcus aureus hyperimmunoglobulinaemia E (hyper-IgE) syndrome. Such a case was investigated in a man suffering from a classic example of the syndrome. Antinuclear antibodies were analysed on a molecular basis. The emergence of immunological and clinical features of systemic lupus erythematosus in patients with defective host defence mechanisms against staphylococcal infections is unlikely to be fortuitous and may help elucidate the pathogenesis of systemic lupus erythematosus. The observations will also aid the long term management of patients with S aureus hyper-IgE syndrome.

Primary hypoventilation (Ondine's curse), due to diminished sensitivity ofthe respiratory center to CO2, is very rare. Up to now only a few patients have been observed, ten of whom were children. Familial occurrence was reported in 1976 for the first time. The cases are described of a 10-year-old girl and her mother who both showed the typical clinical and pathophysiological symptoms. Our own observation also suggests that this unknown defect of respiratory regulation could be inherited. Sedation, anesthesia, or severe respiratory tract infection are life-threatening situations in these patients. Pulmonary hypertension and right heart failure are possible long-term complications.

A preliminary report is presented on survival in 16 children with non-Hodgkin's lymphoma treated since 1975, as compared with that in 31 similar children treated between 1962 and 1974. In the former group, 10 of 14 children (71%) survived one or more years and 5 of 9 children (56%) two or more years with no evidence of disease. In the latter group, the corresponding survival rates were 26% and 19% respectively. This improvement is due to the introduction of an aggressive multidrug chemotherapy combined with radiotherapy, similar to the LSA2-L2 protocol. Considerable toxicity was observed with the new treatment. 23 of the 46 patients with diffuse non-Hodgkin's lymphoma had a Burkitt-type tumor. Treatment failures occurred mainly in children with a Burkitt-type tumor with primary intraabdominal localization.

The incidence of isolated CNS-relapse in the SPOG ALL studies 1976-1986 was analyzed and the prophylaxis of meningosis leucaemica of the different studies was compared. In the SPOG ALL high-risk study 1979-1983, the incidence of isolated CNS-relapse was significantly higher (17/71, 24%) than in the other studies. In this period, radiotherapy was omitted and the prophylactic treatment consisted only of moderately high doses of intravenous methotrexate and intrathecal methotrexate. In other studies, it was shown that the prophylactic combination of CNS-radiotherapy and intrathecal methotrexate, or the periodic administration of combined intrathecal chemotherapy alone, during the whole therapy of 2 1/2 years, produced comparably good results. The prophylaxis with the combined intrathecal chemotherapy was less neurotoxic and allowed the use of a curative radiotherapy in case of a CNS-relapse.

Of 99 patients with acute lymphoblastic leukemia in first bone marrow or isolated CNS relapse seen between 1968 and 1980, 48 were treated without standardized protocol and 51 according to a relapse protocol. Of 16 patients with bone marrow relapse after cessation of the initial treatment 6 survived 8 1/2 years or more, of 66 with bone marrow relapse while on therapy only 4 survived. All of the latter were low risk patients with an initial WBC of less than 20 x 10(9)/l and no enlargement of the mediastinum. All of the 17 patients with isolated CNS relapse died. The relapse protocols used probably improved the chances of children with first bone marrow but not of those with isolated CNS relapse.

After an initial blood and thorax examination, 97 children with ALL were divided into "high risk" and "low risk" groups. From the 20 new "high risk" patients seen between 1972 and 1975 about one quarter were still alive 3 years later, the corresponding proportion from 37 "low risk" patients being about two thirds. Despite increased therapy, the number of early relapses does not appear to have decreased in the new "high risk" cases seen between 1976/77. An investigation of cell surface markers established that T-ALL always occurred in the "high risk" group, whereas B-negative/T-negative ALL was found not only in the "low risk" group but also occasionally in the "high risk" group.

With a cure rate of over 50% pediatric oncology contrasts with the adult oncology. The success is the result of a multimodal approach with surgery, radiotherapy and chemotherapy to almost all forms of childhood cancer as outlined in various national and international protocols. These are evaluated permanently concerning efficacy and toxicity at one organisation (in Switzerland: the pediatric section of the "Schweizerische Arbeitsgruppe für klinische Krebsforschung"). For the care of the children with malignancy however a specialist physician team at a tumor center is not enough. Without the cooperation of the family doctors of the area proper referral of the patients and long term treatment can not be realized. Good information and adequate teaching appears to be necessary to give these patients optimal care.

Since the introduction of cytocentrifugation, the methods of clinical cytology have become more refined. The following advantages should be stressed: 1. speed and ease of processing, 2. highest possible cellular yield, 3. good preservation of cellular characteristics. In the light of predominantly CSF analyses in the field of pediatric oncology the above mentioned findings are clearly illustrated (ALL, AML, reticulum cell sarcomatosis, Ewing sarcoma, leptomeninx sarcoma, retinoblastoma, Letterer-Siwe's disease, familial erythrophagocytic lymphohistiocytosis, plexus papilloma). Malignancies are clearly distinguishable from benign conditions (toxic glial reactions, virus meningitides, CNS hemorrhages etc.). The higher cellular yield permits very early diagnosis of meningeal leukemia. This qualitative improvement of cytological diagnostic methods may considerably influence the choice of therapeutic procedures in the treatment of malignancies.

Cancer is a rare disease in children, in whom some 200 new cases are recorded every year in Switzerland including about 20 in the eastern part of the country. In contrast to cancer in adults, many malignancies of the child have prospects of cure. This improved prognosis is mainly the result of interdisciplinary cooperation within the framework of controlled national and international protocols. Progress in the treatment of two representative forms of cancer (acute lymphocytic leukemia and Wilms tumor) is illustrated. 50% of all children from the eastern part of Switzerland with acute lymphocytic leukemia and 70% of those with Wilms tumor have been cured in the past 7 years. These impressive advances are unfortunately overshadowed by late sequelae of the therapy, which are described and must be taken into account in future therapeutic approaches.