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Biomedical subjects

C Kirch

Publications and source records attributed to C Kirch.

9 recordsLinked to original sources

Acute respiratory distress syndrome after chemotherapy for lung metastases from non-seminomatous germ-cell tumors.

GOALS: To describe an acute respiratory distress syndrome (ARDS) occurring after chemotherapy for non-seminomatous germ-cell tumors (NSGCT) with diffuse lung metastases, we conducted a retrospective study in a 15-bed intensive care unit (ICU) in a comprehensive cancer center. PATIENTS AND METHODS: During a 10-year period, 16 consecutive patients with diffuse lung metastases from a NSGCT were admitted to the ICU for respiratory distress and high-risk chemotherapy. MAIN RESULTS: Nine patients developed acute respiratory failure requiring mechanical ventilation (MV) within 3 days of the initiation of chemotherapy, while the respiratory status of the seven other patients improved. The evolution was independent of tumor marker levels and the type of chemotherapy regimen. The SAPS II score did not accurately describe the severity of this population. The only predictor of intubation was the initial PaO2/FiO2 ratio upon admission to the ICU. Six out of seven patients who did not require MV were discharged alive from the hospital, whereas all but one patient requiring MV died. Refractory hypoxemia and ventilator-associated pneumonia were the leading causes of death. CONCLUSIONS: Acute respiratory distress in patients with lung metastases from NSGCT is a rare cause of ARDS. Chemotherapy could be responsible for triggering the respiratory worsening. Patients with severe respiratory insufficiency (PaO2 <70 mmHg on room air) on admission to hospital should be promptly transferred to the ICU for the first chemotherapy course.

Adult↗

Effect of digoxin on circadian blood pressure values in patients with congestive heart failure.

BACKGROUND: The aim of the study was to investigate the effect of chronic digoxin treatment on circadian blood pressure profile in normotensive patients with mild congestive heart failure. METHODS: In a randomized double-blind, placebo-controlled cross-over protocol, 12 normotensive patients with mild congestive heart failure took digoxin or placebo for a total of 7 days. Automatic 24-h ambulatory blood pressure measurements were carried out at day 7, of either digoxin or placebo. RESULTS: Diastolic blood pressure significantly decreased and systolic blood pressure significantly increased during overnight sleep in the digoxin phase compared to placebo. Digoxin had no effect on either systolic or diastolic blood pressure during daytime. Heart rate decreased in the overnight sleeping phase but did not differ significantly between placebo and digoxin phase. CONCLUSIONS: Digoxin significantly decreases diastolic blood pressure during overnight sleep in patients with congestive heart failure. This effect is likely to be caused by reduction of sympathetic activity or increase of parasympathetic activity. Increase of systolic blood pressure during sleep is probably caused by the positive inotropic effect of the drug.

Aged↗

Human herpesvirus-6 meningoencephalitis in a recipient of an unrelated allogeneic bone marrow transplantation.

BACKGROUND: Human herpesvirus-6 (HHV-6) has been implicated in bone marrow suppression, interstitial pneumonitis, and fatal meningoencephalitis in bone marrow transplant (BMT) recipients. METHODS: We describe the case of a woman with acute myeloid leukemia in second remission who developed febrile meningoencephalitis 8 months after a second unrelated BMT. RESULTS: Computed tomography and magnetic resonance images of the brain were nonspecific. Analysis of cerebrospinal fluid (CSF) revealed lymphocytosis and an increased protein level. Using polymerase chain reaction methods, HHV-6 was the only pathogen detected in CSF, peripheral blood mononuclear cells, and bone marrow. The patient was treated with ganciclovir and foscarnet for 3 months. All clinical manifestations resolved and HHV-6 polymerase chain reaction analysis of CSF became negative 40 days after the beginning of antiviral treatment. CONCLUSIONS: This observation strongly suggests that HHV-6 should be sought in BMT patients with neurological complications and that HHV-6 meningoencephalitis may respond to ganciclovir and foscarnet therapy.

Acute Disease↗

Structural and functional analysis of the cytidine deaminase gene in patients with acute myeloid leukaemia.

Gene transfer of the cytidine deaminase (CDD) cDNA has recently been shown to induce cellular resistance to cytarabine (AraC) in vitro. To investigate the role for CDD in acute myeloid leukaemia (AML) we analysed the CDD activity and CDD gene structure in blast material from well-defined patients with untreated and AraC refractory (RF) AML. Median CDD activity in previously untreated AML was significantly lower than in RF-AML blasts (P=0.015) and was significantly lower in patients with complete remission than with blast persistence following induction chemotherapy (P=0.043). Structural investigation of the CDD gene by Southern analyses and RT-PCR showed no detectable aberrations. Sequence analysis of the CDD cDNA from nine RF-AML patients showed inconsistent aberrations in three patients. Semiquantitative assessment of CDD mRNA expression revealed a significant correlation with CDD activity. In conclusion, concordant with another recent study our data suggest a correlation of pretherapeutic CDD activity with induction treatment response. Besides the previously described prognostic impact of mdrl expression, this result could be useful for the development of risk-adapted AML treatment strategies and warrants further studies of CDD activity in well-defined cohorts of AML patients and of the mechanisms involved in the regulation of CDD activity.

Acute Disease↗

Constitutive overexpression of the cytidine deaminase gene confers resistance to cytosine arabinoside in vitro.

In search of potential therapeutic targets for enhancing the cellular detoxification of cytosine-arabinoside (ara-C), we transfected the human CDD cDNA gene into murine fibroblast cells and examined the effect of increased CDD expression on the cellular resistance to ara-C. Several cell lines were established which consistently demonstrated a 2.5-3.0-fold increase in cellular CDD activity and exhibited an up to 3.0-3.5-fold increase in the IC50 value of ara-C with regard to inhibition of cell proliferation or DNA synthesis, respectively. In the absence of ara-C, these cells maintained unaltered morphology and growth characteristics as compared with parental cells and mock-transfected controls. In addition, we examined the CDD and dCK activity in hematopoietic cells and found CD34+ hematopoietic progenitor cells to reveal a low ratio of CDD/dCK activity. Together, these data suggest that constitutive overexpression of the CDD gene correlates with increased ara-C resistance and thus may prove useful in considering attempts to attenuate ara-C-induced toxicity on hematopoietic progenitor cells.

Adult↗