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Idiopathic thrombocytopenic purpura in children.

ITP in childhood is most often of the acute, self-limited variety, with spontaneous recovery occurring within a matter of days or weeks. In many of these children, acute thrombopenic purpura follows in the wake of a viral infection. While the pathogenesis is not entirely clear, it seem probable that the platelet membrane is altered by virus or by soluble viral antigen-antibody complexes; platelets thus damaged become susceptible to rapid destruction by the RES. Management remains somewhat controversial. While almost all agree that corticosteroid should not be used in all cases of acute childhood purpura, there are still no clear-cut indications for their use, and no real evidence that they are of benefit in reducing the risk of the one rare but serious complication of childhood ITP, namely, intracranial hemorrhage (ICH). In approximately 5-10% of children, ITP ultimately proves to be of the chronic variety, and is in all probability the same condition that is seen in adults. Splenectomy is the treatment of choice, Another small subgroup of children have ITP of the recurrent acute variety; there is some evidence that this entity may also have an autoimmune pathogenesis. Infants born to mothers who have (or have had) ITP often manifest thrombopenia, with or without purpura and other bleeding. While this is generally a benign, self-limited process, requiring no treatment, ICH occurs in a small but significant number of affected infants and probably results from head trauma during delivery.

Acute Disease↗

[A prospective multi-centre study of the response of metastatic gastrointestinal tumours (author's transl)].

In a prospective, multi-centre, randomized study of 109 patients with metastatic gastro-intestinal adenocarcinomas the response rate, survival time and side-effects of two drug combinations, carmustin +5-fluorouracil and carmustin + ftorafur, were compared (same carmustin dosage in both groups). Response to the treatment was 32.7% in those receiving carmustin +5-fluorouracil, 26.3% in those on carmustin + ftorafur. This difference occurred among the 42 patients with gastric adenocarcinoma (33.3% compared with 25%), as well as in 11 with pancreatic adenocarcinoma, and in 56 with colorectal adenocarcinoma (32.1% and 28.6%). Median survival time for 5-fluorouracil + carmustin was 330 days, double that for ftorafur + carmustin (163 days). Bone-marrow toxicity (leukopenia, thrombopenia) was below 10% for both drug combinations. Alopecia occurred in only a few patients. Gastro-intestinal toxicity was common (20% and 18.5%, respectively), but there was no difference between the two groups. The somewhat lower effectiveness of ftorafur compared with 5-fluorouracil was probably due to the deliberately smaller dosage of the former.

Adenocarcinoma↗

[A 42-year-old patient with the hemolytic-uremic syndrome under gemcitabine therapy for an adenocarcinoma of the liver. The hemolytic-uremic syndrome and gemcitabine].

We report on the case of a 42-year-old man suffering from an irresectable adenocarcinoma of the liver. The patient was treated with 5-fluorouracil for 6 months when the disease progressed and second line therapy with gemcitabine was started. After 4 months diastolic blood pressure increased and edema of the legs as well as vomiting occurred. Laboratory tests revealed anemia and thrombopenia accompanied by an elevation of plasma D-dimer, lactatdehydrogenase, creatinine, and urea levels in the serum. In addition, a pronounced proteinuria as well as renal hematuria were detected and subsequently a hemolytic uremic syndrome was diagnosed. After treatment with high-dose glucocorticoids, anticoagulants and transfusions of packed RBC the course of disease improved. Since Gemcitabine is now widely used for treatment of solid organ cancer (e.g. pancreatic adenocarcinoma, biliary tract cancer, lung cancer etc.), it is necessary to be aware of Gemcitabine-induced hemolytic uremic syndrome as a rare but potentially fatal side effect.

Acute Kidney Injury↗

Topotecan in the treatment of refractory neuroblastoma and other malignant tumors in childhood - a phase-II-study.

BACKGROUND: The topoisomerase-I-inhibitor Topotecan (TPT) has shown a broad activity in the therapy of adult malignant diseases. In pediatric oncology TPT has been rarely used. METHODS: From 1/98 to 8/99 we conducted a multicenter phase-II-study of TPT (1.5 mg/m (2)/d in 30 min i. v. for 5 days every 21 days) in pediatric patients (pts) with malignant tumors refractory to conventional therapy (either second line or any relapse). PATIENTS: A total of 20 pts received 81 cycles. The 7 female and 13 male pts had a median age of 10.2 years at the beginning of the TPT therapy. RESULTS: The median number of administered TPT cycles was 4 with an interval of 23.5 days. The median administered TPT dose was 1.48 mg/m (2)/d. No complete responses, but 2 partial responses and 9 stable diseases were observed. In 9 pts the disease progressed. The mean duration until progression for SD was 130 and not different from PR with 131 days. The median cumulative TPT dose until progression in responders was 30 mg/m (2). For all study-pts the median overall survival time was 235 days with 1 pt. still alive. The main toxicity was hematological with anemia grade III/IV (10/42 % of all evaluable TPT cycles), neutropenia grade III/IV (49/18 %) and thrombopenia grade III/IV (35/36 %). Non-hematologic toxicity was mild with the exception of 4 cycles with infection grade III and 1 grade IV. No patient died of therapy-related complications. CONCLUSIONS: TPT as monotherapy has shown an antitumor activity in pediatric pts with various malignancies. Toxicity was mainly hematological and manageable. Further evaluation of TPT treatment is planned using combinations with other cytostatic drugs.

Adolescent↗

Ulcerative colitis in a patient with Wiskott-Aldrich syndrome.

A 30-year-old man with underlying Wiskott-Aldrich syndrome, which is a rare X-linked congenital immunodeficiency syndrome characterized by recurrent infections, thrombopenia, eczema and hematopoietic malignancies, presented with bloody diarrhea. Endoscopic and histological evaluation was compatible with ulcerative colitis. Congenital immune defects are paralleled by enterocolitis mimicking inflammatory bowel disease in a substantial number of patients. Despite therapy with prednisolone and 5-ASA compounds, the patient described here experienced a relapse of the colitis twice. Subsequently a JC virus infection of the central nervous system was diagnosed, and he died due to progressive multifocal leukencephalopathy.

Adult↗

Weekly oxaliplatin, high-dose folinic acid and 24h-5-fluorouracil (FUFOX) as salvage therapy in metastatic colorectal cancer patients pretreated with irinotecan and folinic acid/5-fluorouracil regimens.

UNLABELLED: Irinotecan (CPT-11), oxaliplatin (OXA) and different folinic acid(FA) modulated 5-fluorouracil (5-FU) regimens are active as first-and second-line chemotherapy of metastatic colorectal cancer. However, the best palliative sequence of these substances is still unclear. After CPT-11 containing regimens the optimal salvage protocol has not yet been defined. Here, we retrospectively analysed the weekly ambulant combination of OXA with continuous FA/5-FU (FUFOX) after two different CPT-11 containing chemotherapeutic regimens. PATIENTS: During October 1999 and May 2001, 20 patients (median 62; 48-74 years) were included who had disease progression after CPT-11 /bolus FA/5-FU (Saltz; 7 patients, group A) or after FA/5-FU followed by CPT-11 alone (13 patients, group B). OXA(60 mg/m2) was given for 2 hours prior to FA (500 mg/m2) as 2 h-infusion and continuous 5-FU (2.600 mg/m2) for 24 h-infusion on day 1,8,15 and 22 (repeated after week 6). RESULTS: FUFOX was administered 252 times. About 1,203 mg OXA per patient was given. Toxicities NC-CrC grade 3 were observed in 10 patients: diarrhoea (4), mucositis (5), nausea/vomiting (2), anaemia (1), leucopenia (1), thrombopenia (1) and hand-foot-syndrome (1), 3 patients showed minor remissions, II patients stable disease. The median time to progression was 16(0-39) weeks. The median survival from start of FUFOX and from start of any palliative therapy was 33 (5-65) and 99 (44-200) weeks for all patients, respectively. CONCLUSIONS: FUFOX was efficient for additional tumour control in 70% of patients pretreated with CPT-11/5-FU based regimens. Sequential palliative treatment can lead to prolonged survival.

Aged↗

[Clinical presentation and management of the severe acute respiratory syndrome (SARS)].

BACKGROUND AND OBJECTIVE: In February 2003, a newly emerged infectious disease was described, the etiology of which was initially unknown. It is referred to under the term SARS. In the beginning, it spread in some regions South-East Asia. Import infections appeared in many other parts of the world. Based on the first cases in Germany, this report illustrates the clinical appearance, the diagnostic results and the management of this new disease. PATIENTS AND METHODS: We analysed the data of two patients with SARS and one suspected patient. The results of radiological, laboratory, microbiological and physical examinations were abstracted and compared with the data obtained in other regions. RESULTS: Two of the three patients under our care developed SARS disease. This is characterised by fever of sudden onset lasting for more than 5 days, rapidly changing consolidations in chest x-ray not affected by antimicrobial therapy, leuko-, lympho- as well as thrombopenia with a compromised pulmonary function later in the course. Close contacts with SARS patients does not regularly result in full development of the disease. Secretion of a coronavirus could be detected in respiratory samples during the febrile phase and in feces for a longer time. It is still an open question whether bedrest and antibiotic prophylaxis by themselves or an additional administration of ribavirin and corticosteroids can improve the outcome. CONCLUSION: SARS is a new and highly contagious lung disease. It is crucial to be able to recognize the clinical appearance and the diagnostic features of this disease at an early stage, in order to prevent a further dissemination of the disease.

Adult↗

[Mitomycin-induced hemolytic-uremic syndrome].

HISTORY AND CLINICAL FINDINGS: A 58-year-old patient suffered from rapidly progressing renal insufficiency and 11 kg weight-loss three months after adjuvant treatment of a carcinoma of the lower bowel (G 2 T 3 N 1 M 0 ) with mitomycine C. At the point of hospitalisation the patient was anuric while suffering from pulmonary oedema, hemolytic anemia and thrombocytopenia. INVESTIGATIONS: Computed tomography and bronchial endoscopy showed pulmonary haemorrhage. Recurrence of carcinoma or metastases were excluded. Renal biopsy revealed mesangiolysis and concentric intimaproliferation (onion skinning). Beside haemolytic anaemia and fragmentocytes toxic damage of the bone marrow was found. TREATMENT AND COURSE: After one week treatment in the intensive care unit because of respiratory insufficiency recovery was observed under plasma separation and high dose corticosteroid therapy. Disease activity involved renal failure, bone marrow insufficiency, microangiopathic anaemia thrombopenia and pulmonary haemorrhage. CONCLUSION: Lung involvement in the course of haemolytic uremic syndrome is rare and carries a high lethality. The case illustrates the need of detailed diagnostic for correct treatment of haemolytic uremic syndrome. If chemotherapy is required in patients with pre-existing or intercurrent renal failure dose adaptation is necessary to avoid dose-dependent toxicity of mitomycine C.

Antibiotics, Antineoplastic↗

Short- and long-term outcome after lung resection for invasive pulmonary aspergillosis.

BACKGROUND: Lung resection for invasive pulmonary aspergillosis (IPA) is controversial. Neutropenia, thrombopenia and poor general condition may increase perioperative morbidity and mortality, and the redeeming benefit is questionable. Therefore we analyzed short- and long-term outcome after lung resection for IPA. METHODS: 41 patients with hematological disease underwent lung resection for suspected IPA: lobectomy (23 patients), wedge-resection (16) and enucleation (2). RESULTS: 4 (10%) patients developed major complications: pleural aspergillosis, bronchial stump insufficiency, severe bleeding, ARDS. 11 (27%) patients showed minor complications: pleural effusion (6), pneumothorax (2), seroma (2) and hematothorax (1). 30-day mortality was 10 % (4 of 41 patients): two died of bacterial septicemia, two of disseminated aspergillosis. One (2%) death was possibly surgery-related. IPA was cleared in 87% of patients, fungal relapse occurred in 4 (10%) patients. Overall survival was 65%, 58% and 40% at 6 months, 12 months and 5 years. CONCLUSION: Lung resection for IPA even in profound cytopenia is feasible with acceptable morbidity and mortality. Fungal infection can be cured in more than 80 % of patients. Long-term outcome can be achieved if the hematological disease is under control.

Adolescent↗

[Disseminated intravascular coagulation, perimyocarditis and bilateral pleural empyema in adult Still's disease].

HISTORY: A 21-year-old man was admitted to the hospital because of high fever, arthralgias and myalgias. One week before he was treated with penicillin G orally because of cough and sore throat. PHYSICAL EXAMINATION: The critically ill patient presented with a red throat and cervical lymphadenopathy. Lung auscultation revealed reduced respiratory sounds at both base, heart auscultation revealed a pericardial friction rub. Dermatologic examinations were normal. INVESTIGATIONS: Laboratory findings were notable for anemia, thrombopenia and leukocytosis, disseminated intravascular coagulation and markedly elevated CRP (309 mg/l). Electrogram showed inferior and lateral ST segment depression. Echocardiography showed pericardial effusion. Chest CT scan revealed bilateral pleural effusion, a left-sided small infiltrate and enlarged mediastinal lymph nodes. Abdominal ultrasound confirmed hepatosplenomegaly and ascites. TREATMENT AND CLINICAL COURSE: A diagnosis of parapneumonic bilateral pleural empyema, perimyocarditis and disseminated intravascular coagulation was made. Despite institution of empiric antibiotic therapy, no clinical improvement was observed. After exclusion of infectious, autoimmune or malignant disease, clinical and laboratory data, especially marked hyperferritinemia, helped to establish the diagnosis of adult-onset Still's disease. Immunosuppressive treatment with prednisolone and azathioprin resulted in remission. CONCLUSION: Adult-onset Still's disease is a rare inflammatory disorder of unknown origin, which may affect multiple organs. The diagnosis is based on a diagnostic score, which includes a number of clinical and laboratory findings, published by Yamaguchi in 1992. Marked hyperferritinemia represents an additional diagnostic clue to the disease.

Adult↗

[Amrinone for cardiovascular therapy in hypodynamic septic patients?].

Pulmonary hypertension, systemic vasodilation and the supply dependency of oxygen uptake are the major problems associated with sepsis. Thus, the goal of haemodynamic therapy in septic patients is an increase in cardiac output large enough to permit adequate tissue oxygenation. The purpose of this study was to establish whether the additional use of the phosphodiesterase inhibitor amrinone is useful in hypodynamic septic patients with inadequate tissue perfusion. Nine patients who had developed the clinical signs of sepsis (temperature greater than 38.5 degrees C, leukocytosis greater than 15,000/mm3, thrombopenia less than 100,000/mm3 or a drop in platelet count greater than 30%, cardiovascular shock) were given amrinone 30 micrograms.kg-1.min-1 for one hour. All patients showed mixed venous oxygen saturations below 70% and oxygen extraction rates above 30%, despite maximum catecholamine therapy. Haemodynamic parameters were measured with the help of a pulmonary artery catheter. Statistical significance was checked using the Wilcoxon signed-ranks test. During amrinone application cardiac index increased significantly from 4.6.1.81.min-1.m-2 to 5.6 +/- 1.81.min-1.m-2 (p less than 0.01), while central venous pressure was kept constant by volume supply. Mean pulmonary artery pressure remained nearly unchanged, whereas mean arterial pressure dropped significantly from 91 +/- 13 mmHg to 75 +/- 8 mmHg (p less than 0.01). The oxygen supply rose during administration of amrinone by an average of 17%, which led to a rise in oxygen uptake. Independence of oxygen uptake from oxygen supply, however, could not be attained. In septic patients, amrinone increases cardiac output via pulmonary vasodilation. However, pronounced systemic vasodilation lowers arterial blood pressure, enhancing the risk of myocardial ischaemia.

Aged↗

[Septic-toxic heart failure as a result of a heparin-induced thrombocytopenia with "white-clot-syndrome"].

A patient is presented who developed pulmonary artery embolism and thrombocytopenia with various arterial clots several days after an ankle joint osteosynthesis, which finally caused the amputation of the right arm. Unfractionated heparin was applied for the prevention of postoperative thrombosis. Obviously as a consequence of the liberation of toxic metabolites from the gangrenous lower arm, the patient developed septic shock which was exacerbated by a severe pneumonia caused by methicillin-resistant S. aureus bacteria (MRSA). Laboratory investigations showed an antibody (IgG) induced thrombopenia mediated by all low molecular weight and unfractionated heparins. By eliminating heparin and further treatment with a low molecular weight heparinoid (ORG 10,172), platelet count rose sufficiently and thrombotic process ceased completely. Septic shock was successfully treated by fluid replacement, antibiotics and inotropic substances.

Adult↗

[Therapy realization and complications in the BFM-83 therapy study of acute myelogenous leukemia].

Data on the realization of therapy are available for 159 out of 173 (92%) protocol patients included in the study AML-BFM-83. The induction therapy could be carried out according to protocol in almost 80% of patients, with a dose compliance (= actual dose/prescribed dose) of greater than or equal to 80% for all substances. During the second therapy phase (consolidation) considerable deviations from the recommended therapy occurred in all nonresponders and in 34% of the patients who had achieved remission. The maintenance therapy had to be reduced in one third of the patients, mainly due to thrombopenias. Lethal complications caused by therapy-induced toxicity, occurred in 7 out of 173 cases (4%), and followed severe infections (mycoses), or other complications such as cardiotoxicity. The proportion of severe complications decreased from the induction through the first to the second consolidation phase. They were rare during maintenance therapy, but markedly more frequent in nonresponders and in children with early relapse (within 12 months). In view of the small differences in dose compliance, it is difficult to determine the prognostic significance of the realization to therapy. With the application of the COX regression and special life table analyses the dose compliance decreases in significance after including the known initial prognostic factors.(ABSTRACT TRUNCATED AT 250 WORDS)

Antineoplastic Combined Chemotherapy Protocols↗

[Necrotizing enterocolitis (NEC) - pathogenesis and therapy (author's transl)].

The clinical courses in 39 children with NEC were studied to answer questions about pathogeny and the indication for surgical treatment. Anamnestic, clinical and hematological findings show an ischemia to be the "conditio sine qua non". Disseminated intravascular coagulation does not seem to be the primary cause of the disease. Whether bacterial infections of the intestinal wall are of importance in the pathogeny cannot sufficiently be proven on the available findings. The clinical symptoms, the number of platelets and the level of serum-sodium make it possible to classify NEC in four stages with typical morphologic appearance. The results of an early and of a late treatment by operation are compared and it is deduced that the best moment for surgical intervention will be the change from stage II to stage III. Symptoms of stages II/III are the progressive clinical course with increasing intestinal bleeding, edema of the abdominal wall and scrotum, thrombopenia and low sodium level.

Child↗

[Chemotherapy of nonendemic Burkitt's lymphoma].

14 patients (12 men, 2 women, mean age 26.3 [15-47] years) with histologically confirmed Burkitt's lymphoma were subjected between 1984 and 1989 to chemotherapy originally developed for treating lymphomas in children. Treatment consisted of medium doses of methotrexate, cyclophosphamide, teniposide, cytarabine, adriamycin and prednisone, intrathecal administration of methotrexate and if necessary prophylactic or therapeutic irradiation of the cranium. Most of the patients (64%) were in advanced stages of the disease. The rate of complete remissions was 100%. Four patients (29%) had a recurrence. Side effects were leukopenia (WHO grade III and IV) in 71%, grade III anaemia in 43% and grade III-IV thrombopenia in 29% of the patients. Considerable mucositides in 5 of the 14 patients (36%), and in one case a tumour lysis syndrome with transient renal insufficiency were other therapy-induced side effects. These results suggest that this treatment course can be successful also in non-endemic Burkitt's lymphoma in adolescents and adults.

Adolescent↗

[Hemolytic-uremic syndrome in an adult with T-cryptantigen liberation].

Haemolytic uraemic syndrome was diagnosed in a 36-year-old woman with acute renal failure (creatinine 10.5 mg/dl), haemolytic anaemia (haemoglobin 9.7 g/dl, lactate dehydrogenase 1926 U/l) and thrombopenia (98,000/microliters). After initial plasmaphereses and high doses of furosemide all symptoms disappeared within three weeks. The lectin tests demonstrated that the illness was connected with the liberation of T-crypt-antigen (Thomsen-Friedenreich antigen) on the erythrocytes. This special form of the haemolytic uraemic syndrome (neuraminidase-induced haemolytic uraemic syndrome) has previously been observed almost exclusively in children. However, for diagnosis and differentiation of haemolytic uraemic syndromes the presence of liberated T-antigen on erythrocytes should also be tested for in adults.

Acute Kidney Injury↗

[Cytomegaly infection in infancy in a family with demonstrated HIV antibodies].

Cytomegalovirus (CMV) was isolated from the urine of babies from two consecutive pregnancies of a mother. The first baby had died of pneumonia at the age of six months, two years before the second confinement (twins of different sexes). The male twin was examined at the age of eight months on account of generalized lymphomas, pulmonary infiltrates and thrombopenia. He excreted CMV in the urine, and HIV antibodies were found in the serum. All members of the family (also the baby who died in 1983, from whom serum samples had been stored at -20 degrees C) finally proved to be carriers of antibodies against HIV. The parents and the female twin did not show any clinical symptoms indicating a HIV infection; however, CMV was also isolated from a urine sample from the mother.

Acquired Immunodeficiency Syndrome↗

Immunological alterations associated with Plasmodium vivax malaria in South Korea.

Various haematological and immunological studies on patients infected with Plasmodium vivax were undertaken, at diagnosis (day 0), after treatment with chloroquine but during primaquine treatment (day 10) and after all treatment (day 59), in South Korea (where there has been a recent and abrupt increase in the incidence of such infection). The main aims were to gain an understanding of the haemto-immunological alterations of this malarial infection, both before and after treatment, and to identify at least one useful marker for the diagnosis and post-treatment monitoring of P. vivax malaria. Thirty-eight patients with P. vivax malaria were compared with 20, apparently healthy controls. At diagnosis, the patients had lymphopenia, marked eosinopenia (the eosinophil count being correlated with the platelet count) and thrombopenia. Cells of most of the lymphocyte subsets investigated [i.e. CD3+, CD8+, CD19+, CD56+, CD3-/CD56+ and CD8+/CD56+ but not CD4+, CD3+/CD56+ or CD25+] were significantly less common among the lymphocytes of patients at diagnosis than among those of the controls. After initiating treatment, the numbers of CD19+ lymphocytes gradually increased (to normal values by day 59), whereas those of CD3+/56+ lymphocytes remained abnormally low throughout the follow-up period. The proportions of lymphocytes identified as CD4+ appeared to be unaffected by treatment. Although serum concentrations of IgE (and, to a lesser extent, IgM) were elevated in the patients at diagnosis, they were subnormal on day 10 post-treatment and normal at the day-59 follow-up. Serum concentrations of IgG and IgA in the patients were always found to be similar to those in the controls. At diagnosis the serum concentrations of complements C3 and C4 were significantly elevated in the patients. C3 remained at the same high concentration during follow-up but the concentration of C4, like that of IgE, was found to be subnormal on day 10 and normal 7 weeks later. The level of parasitaemia (%) was only found to be significantly correlated with haemoglobin concentration. The observation of eosinopenia with elevated IgE and C4 could be a useful indicator of P. vivax malaria, and treatment response could be followed by serial monitoring of serum concentrations of IgE and C4.

Adolescent↗