Perforin-mediated cytotoxicity is important for controlling viral infections, but also for limiting immune reactions. Failure of this cytotoxic pathway leads to hemophagocytic lymphohistiocytosis (HLH), a life-threatening disorder of uncontrolled T-cell and macrophage activation. We studied susceptibility to HLH in 2 mouse strains (souris and beige J ) and a cohort of patients with partial defects in perforin secretion resulting from different mutations in the LYST gene. Although both strains lacked NK-cell cytotoxicity, only souris mice developed all clinical and histopathologic signs of HLH after infection with lymphocytic choriomeningitis virus. The 2 strains showed subtle differences in CTL cytotoxicity in vitro that had a large impact on virus control in vivo. Whereas beige J CTLs eliminated lymphocytic choriomeningitis virus infection, souris CTLs failed to control the virus, which was associated with the development of HLH. In LYST-mutant patients with Chediak-Higashi syndrome, CTL cytotoxicity was reduced in patients with early-onset HLH, whereas it was retained in patients who later or never developed HLH. Thus, the risk of HLH development is set by a threshold that is determined by subtle differences in CTL cytotoxicity. Differences in the cytotoxic capacity of CTLs may be predictive for the risk of Chediak-Higashi syndrome patients to develop HLH. (Blood. 2011; 118(17):4620-4629)
A retrospective study of 28 patients identified with subdural empyema (SE) at the Department of Neurosurgery between the years 1995 and 2005 was carried out. SE occurred in all patients following bacterial meningitis. The six most frequently encountered clinical features included: (1) fever in 22 (79%) patients; (2) disturbed consciousness in 16 (57%) patients; (3) papilledema in 11 (39%) patients; (4) hemiparesis in 4 (14%) patients; (5) meningismus or meningeal signs in 4 (14%) patients, and (6) seizures in 3 (11%) patients. In the majority of cases, the most frequent causative pathogen of SE was Staphylococcus aureus. Surgery was performed on all patients, which included craniotomy in a group of 20 patients and burr hole drainage in a group of 8 patients. In conclusion, we believe that infants and young children should be carefully monitored following meningitis, in case of SE development, and that surgical intervention in patients presenting with meningitis may facilitate the development of SE. Furthermore, from a surgical point of view, our experience has led us to believe that craniotomy in comparison with burr hole surgery is the best surgical modality for management of SE as the recurrence rate of SE associated with burr hole surgery is high.
Our data suggest that disseminated intravascular coagulation score greater than or equal to 5 can be used in the definition of high-risk patients. Early recognition of poor risk factors has important prognostic and therapeutic implications.
The incidence of hematological malignancies during pregnancy is low, and treatment in this setting is problematic. This study observed 21 pregnancies in 18 patients with hematological malignancies. Patients' ages were between 19 and 43 (median 25) years. Two pregnancies ended with spontaneous abortion, one pregnancy ended with in utero death, three therapeutic abortions were carried out, and 15 infants were born alive but three of them died later. The median birth weight was 2.47 kg. Twelve babies survived to a median age of 36 (range 4-117) months. Eight babies were exposed to chemotherapy during the in utero period. One baby was exposed to chemotherapy during all the trimesters and was born prematurely and later died because of intracranial bleeding. Four babies were exposed to chemotherapy during the first trimester, one of them had low birth weight and floating thumb malformation, two of them had only low birth weight, and one was born healthy, but died at 3 months of age as a result of severe gastroenteritis. Two babies were exposed to chemotherapy during the second and third trimesters; one of them had low birth weight, and the other pregnancy ended in in utero death. One infant was exposed to chemotherapy during the third trimester and was born at term, but died because of pulmonary hemorrhage. We concluded that chemotherapy during all trimesters of pregnancy carries a significant risk for an unfavorable outcome.
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