Recombinant human granulocyte colony-stimulating factor enhanced cytotoxicity of Ara-C in Ara-C-resistant leukemic cells from a patient with biphenotypic leukemia in cell kinetic quiescence.

In vitro preincubation with recombinant granulocyte colony-stimulating factor(rhG-CSF, 100 ng/ml) enhanced the cytotoxicity of 1-beta-D-arabinofuranosylcytosine(Ara-C) in leukemic cells resistant to Ara-C from a patient with biphenotypic leukemia. Treatment of the cells with rhG-CSF resulted in a 17-fold increase in DNA synthesis, 4.6-fold increase in percentage of S-phase, and a two-fold increase in Ara-CTP formation. Maximal effect was observed at 72 h of incubation. Combination chemotherapy with rhG-CSF and Ara-C to the patient showed remarkable cytoreduction. These results indicate that recruitment of resistant leukemic cells in cell kinetic quiescence is inducible by rhG-CSF and that it is possible enhancement of the cytotoxicity to cell cycle-specific drugs such as Ara-C.     

Hyperaemia prior to acute cerebral swelling in severe head injuries: The role of transcranial doppler monitoring

Summary Acute cerebrovascular congestion after a closed head injury is significantly related to intracranial hypertension. As an indirect method of cerebral blood flow measurement, transcranial doppler sonography (TCD) provides a rapid and noninvasive assessment of cerebral haemodynamics, including hyperaemic conditions.TCD examinations was serially performed in 35 patients with severe head injury with intact cerebral circulation; i.e. the mean flow velocity (MFV) patterns of the middle cerebral artery (MCA) did not show signs of cerebral circulatory arrest such as systolic spike, to and fro, or no flow. The results showed that the MFV of the MCAs and ipsilateral extracranial internal carotid arteries (ICAs) in 9 of these patients increased sharply and pulsatility index (PI) decreased during 48–96 hours after the injury. This was soon followed by patterns of high intracranial resistance, consistent with elevated intracranial pressure (ICP) in monitored patients and acute brain swelling on repeated computed tomographic (CT) scans. The correlation between increased MFVs, decreased PIs, and cerebral haemodynamic changes leading to acute brain swelling is discussed.The number of patients who ended with severe disability, vegetative state, or death was 66% in this group of 9 patients, compared to only 34% for the 35 patients overall with severe head injury. Though the morbidity and mortality rates largely depend on the primary injury, the presence of acute cerebral swelling aggravate the grave course in these patients. And the ability of TCD to monitor the hyperaemic state prior to oedema should lead us to adjust the therapy in order to minimize the secondary insult related to intracranial hypertension.     

A case of coronary sinus rupture following retrograde coronary perfusion for myocardial protection

A 48-year-old woman was admitted to our hospital suffering from chest and back pain. The aortogram and CT scanning revealed aortic dissection (DeBakey II type). Six days after onset, the emergent operation was carried out under the cardio-pulmonary bypass. Myocardial protection was made by retrograde coronary sinus perfusion (RCSP) with cold GIK. The ascending aorta was replaced with an artificial graft including the entry. Massive bleeding in the pericardial space and the rupture of coronary sinus was recognized immediately after declamping of the aorta. Repair was made successfully under induced electric ventricular fibrillation. Care for RCSP was discussed.     

Lateral position prevents respiratory occlusion during surgical procedure under general anesthesia in the patient of huge anterior mediastinal lymphoblastic lymphoma

Lymphoblastic lymphoma, an aggressive mediastinal mass, is recognized as serious threat to the patient in developing cardiac tamponade or airway obstruction. Surgical procedure is often required to relieve clinical emergency and to establish prompt pathological diagnosis. However, in such a patient, acute respiratory occlusion in the spine position can be a life-threatening complication during general anesthesia. We describe a 17-year-old man whose cardiac tamponade was treated by pericardial-pleural window through a left anterior thoracotomy in the lateral position. The patient recovered from hemodynamic compromise without showing respiratory occlusion during general anesthesia and remained in the lateral position until extubation. Pathological diagnosis was precursor T-lymphoblastic lymphoma. There were no complications attributable to the operative procedure. Further chemotherapy reduced the mediastinal mass in size after two weeks when the patient developed sepsis and died. Lateral position prevents respiratory occlusion during surgical procedure under general anesthesia in the patient of huge anterior mediastinal tumor with airway obstruction.     

‘Ischemic tolerance’ phenomenon detected in various brain regions

We investigated the effects of mild and non-lethal ischemic insult on neuronal death following subsequent lethal ischemic stress in various brain regions, using a gerbil model of bilateral cerebral ischemia. Single 10-min ischemia consistently caused neuronal damage in the hippocampal CA1, CA2, CA3 and CA4, layer III/IV of the cerebral cortex, dorsolateral part of the caudoputamen and ventrolateral part of the thalamus. On the other hand, in double ischemia groups, 2-min ischemic insult 2 days before 10-min ischemia exhibited significant protection in the CA1 and CA3 of the hippocampus, the cerebral cortex, the caudoputamen and the thalamus. Five-min ischemic insult 2 days before 10-min ischemia also showed protective effect in the same areas as those of 2-min ischemia except for the CA1 region of the hippocampus, while 1-min ischemic insult exhibited no protective effect in any brain regions. In the immunoblot analysis, both 2- and 5-min ischemia caused increased synthesis of heat shock protein 72 (HSP 72) in the hippocampus, but 1-min ischemia did not. The present study demonstrated that the ‘ischemic tolerance’ phenomenon was widely found in the brain and also suggested that ischemic treatment severe enough to cause HSP 72 synthesis might be needed for induction of ‘ischemic tolerance’.     

Acute hemorrhagic colitis induced by the neuraminidase inhibitor oseltamivir]

A 23-year-old woman had lower abdominal pain, diarrhea and bloody stool was admitted and given a diagnosis of influenza B. Her home doctor had started treatment by neuraminidase inhibitor (oseltamivir) the previous day. Colonoscopic examination revealed an area of hemorrhage and erosion in the left transverse colon. After halting oseltamivir treatment these symptoms disappeared and her colonoscopic findings improved. A drug-induced lymphocyte stimulation test was positive for oseltamivir. This case is the first reported case of acute hemorrhagic colitis induced by oseltamivir.     

Relationship between the thromboxane A2 receptor gene and susceptibility to cerebral infarction.

The risk of cerebral infarction (CI) in an individual is dependent on the interplay between genetic risk factors and environmental influences. Binding of thromboxane A2 (TXA2) to its receptor (TP) modulates thrombosis/hemostasis and plays a significant role in the pathogenesis of CI. The aim of the present study was to investigate the relationship between human TP gene single nucleotide polymorphisms (SNPs) and haplotypes and CI in a Japanese population. A genetic association study was performed in 194 CI patients and 365 non-CI subjects by specifically characterizing 6 SNPs in the human TP gene (rs2271875, rs768963, rs2238634, rs11085026, rs4523 and rs4806942). Analysis demonstrated that there were significant differences in the overall distribution of genotypes and dominant or recessive models of rs2271875 and rs768963 between the CI and the non-CI groups. Multiple logistic regression analysis revealed that the C allele of rs768963 was significantly associated with CI (p = 0.029), even after adjusting for confounding factors (odds ratio: 2.41). Further, the C-T-C haplotype of rs768963-rs2238634-rs4806942 was significantly more frequent in the CI group (23.0%) than in the non-CI group (17.7%). These results suggest that specific SNPs and haplotypes may have utility as genetic markers for the risk of CI and that TP or a neighboring gene is associated with the increased susceptibility to CI.     

Screening of H-ras Gene Point Mutations in 50 Cases of Bladder Carcinoma

Background Mutation converts the H-ras gene into an activated oncogene in about 10% of human bladder cancers. Codons 12 and 61 are the major "hot spots" for activation. A simple and accurate method to detect point mutations in these codons may be clinically useful for early diagnosis of bladder cancer.
Methods Bladder cancer samples from 50 patients, plus 10 samples of normal bladder mucosa, were analyzed for possible point mutation of the H-ras gene at either codon 12 or codon 61. The H-ras gene DNA segments that include these 2 codons were amplified by PCR methods, then the possible presence of a point mutation was evaluated at each codon by susceptibility of the respective DNA segments to digestion with the restriction enzyme and by dot blot hybridization assay. A bladder cancer patient who had an H-ras gene mutation was examined to see whether the mutation was also detectable in the cells released in the urine.
Results Definite or possible point mutations were found in 6 (1 2%) out of 50 bladder cancer patients, while no mutation was detected in normal mucosa. A point mutation could also be detected in cells isolated from the patient's urine sample.
Conclusion The prevalence of point mutations at codon 1 2 or codon 61 of the H-ras gene found in this study was similar to that previously estimated for human bladder cancer by DNA transfection assay. The method we have used for detecting point mutations of the H-ras gene provides a simple and highly accurate way to detect mutated cancer cells even in the urine. It may be clinically usable for early diagnosis of bladder cancer.