Successful immune reconstitution decreases leukemic relapse and improves survival in recipients of unrelated cord blood transplantation.

Allogeneic hematopoietic stem cell transplantation (HSCT) is established therapy for selected patients with acute leukemia. After transplantation, antileukemic immune responses are believed to eliminate residual leukemia cells and decrease the likelihood of relapse. However, the clinical effect of successful antigen-specific immune reconstitution after HSCT on the likelihood of leukemic relapse and overall survival is not known. Pediatric recipients of unrelated cord blood transplants who underwent transplantation for acute leukemia were sequentially evaluated for their development of antigen-specific T-lymphocyte immunity to herpes viruses. The clinical effect of a positive antigen-specific response on relapse-free survival was determined. The presence of an antigen-specific response resulted in a relapse-free survival advantage (P = .0001), which was primarily due to a decrease in leukemic relapse (P = .003). Proportional hazards modeling for time to relapse and time to relapse or death defined 3 variables that were strongly associated with a poor outcome: female gender, poor remission status before transplantation, and negative antigen-specific T-lymphocyte proliferation. Notably neither acute nor chronic graft-versus-host disease had any effect on the incidence of leukemic relapse. Successful antigen-specific immune reconstitution after unrelated cord blood transplantation results in decreased leukemic relapse and improved overall survival.     

Expression and CpG methylation of the insulin-like growth factor II gene in human smooth muscle tumors.

Previously we have shown that expression of the insulin-like growth factor II (IGF-II) gene in 36 normal smooth muscle tissues (myometria) and 26 benign smooth muscle tumors (leiomyomas) was detectable by Northern blot analysis but that the RNA levels were low. In 9 of 20 malignant smooth muscle tumors (leiomyosarcomas) IGF-II gene expression was also low or absent, while in 11 of 20 the IGF-II gene was abundantly expressed. In 32 of these tissues we have now studied the DNA methylation state of the IGF-II gene. For the analysis of overall methylation of the gene the restriction endonucleases HpaII and MspI were used. In normal smooth muscle and in leiomyomas the IGF-II gene appeared to be methylated. In leiomyosarcomas with low IGF-II gene expression the DNA was partly demethylated. In leiomyosarcomas with abundant IGF-II gene expression overall methylation of the DNA tended to be low. In addition, we have studied the methylation state of one particular CpG site in the IGF-II gene with the restriction endonuclease AvaII. The results of the latter analysis confirm the analysis with HpaII and MspI. In conclusion, in malignant smooth muscle tumors the data indicate an inverse correlation between CpG methylation and expression of the IGF-II gene.     

Translocation of BCR to chromosome 9: A new cytogenetic variant detected by FISH in two Ph-negative,BCR-positive patients with chronic myeloid leukemia

Leukemic cells from two patients with Philadelphia-negative chronic myeloid leukemia (CML) were investigated: I) Cytogenetics showed a normal 46.XY karyotype in both cases, 2) molecular studies revealed rearrangement of the M-BCR region and formation of BCR-ABL fusion mRNA with b2a2 (patient I) or b3a2 (patient 2) configuration, and 3) fluorescence in situ hybridization (FISH) demonstrated relocation of the 5′ BCR sequences from one chromosome 22 to one chromosome 9. The ABL probe hybridized to both chromosomes 9 at band q34, while two other probes which map centromeric and telomeric of BCR on 22q 11 hybridized solely with chromosome 22. For the first time, a BCR-ABL rearrangement is shown to take place on 9q34 instead of in the usual location on 22q 11. A rearrangement in the latter site is found in all Ph-positive CML and in almost all investigated CML with variant Ph or Ph-negative, BCR-positive cases. The few aberrant chromosomal localizations of BCR-ABL recombinant genes found previously were apparently the result of complex and successive changes. Furthermore in patient 2, both chromosomes 9 showed positive FISH signals with both ABL and BCR probes. Restriction fragment length polymorphism (RFLP) analysis indicated that mitotic recombination had occurred on the long arm of chromosome 9 and that the rearranged chromosome 9 was of paternal origin. The leukemic cells of this patient showed a duplication of the BCR-ABL gene, analogous to duplication of the Ph chromosome in classic CML. In addition they had lost the maternal alleles of the 9q34 chromosomal region. The lymphocytes of patient 2 carried the maternal chromosome 9 alleles and were Ph-negative as evidenced by RFLP and FISH analyses, respectively. © 1993 Wiley-Liss, Inc.     

Long-Term Subdural Strip Electrocorticographic Monitoring of Ictal Déjà Vu

Summary: We report a series of 8 patients with ictal déjà vu. Subdural strip electrocorticographic (ECoG) monitoring localized the ictal epileptogenic focus as follows: right (n = 6) and left (n = 2) mesiotemporal lobe. In all 8 patients, the left hemisphere was dominant for language function based on intracarotid amytal testing. In 6 right-handed patients, ictal déjà vu was associated with a right temporal lobe focus. However, in the 2 left-handed patients, the ictal focus was left temporal lobe. Although ictal déjà vu localizes the epileptic focus to temporal lobe, this experiential phenomenon appears to lateralize to the hemisphere nondominant for handedness.     

Time course of the effects of diazepam and lorazepam on perceptual priming and explicit memory

The effects of diazepam and lorazepam on explicit memory and perceptual priming were studied 50, 130 and 300 min after drug administration. Sixty healthy volunteers were randomly assigned to one of five parallel groups (placebo, diazepam 0.2 or 0.3 mg/kg, lorazepam 0.026 or 0.038 mg/kg). The corresponding doses of benzodiazepines exerted a similar negative effect on explicit performance. Lorazepam markedly impaired priming performance, whereas the effect of diazepam was intermediate between that of placebo and that of lorazepam 0.038 mg/kg. The impairment was maximal at the theoretical peak plasma concentration. Contamination by explicit memory could account for the decrease in priming performance observed in the diazepam groups.     

Exposure to pesticides in ambient air

Abstract: Ambient air was monitored for pesticides at four sites in Coffs Harbour, a coastal town (population about 50 000) surrounded by banana plantations. Air was sampled continuously for five consecutive months during the peak agricultural spraying period using vacuum pumps set to sample one litre per minute through ORBO-42 adsorption tubes. Six pesticides were detected: three organochlorines and three organophosphates. The most commonly detected pesticide (14 per cent of all samples) was chlor-pyrifos (maximum detected level 208.0 ng/m³, mean 3.6 ng/m³). Heptachlor was detected in 7.1 per cent of all samples (maximum detected level 133 ng/m³, mean 2.7 ng/m³). Other pesticides were only rarely detected. The only pesticide applied by air in the district (propiconazole) was not detected. If international health guidelines are used as a yardstick, these levels of exposure appear unlikely to present an appreciable health risk. Chlorpyrifos detection was associated with low wind speed (P = 0.012) and high temperature (P = 0.015), and detection at one site was associated with detection at another (P < 0.001). Chlorpyrifos detection was also associated with domestic applications within the town area as reported by pesticide applicators (P = 0.045). Peak agricultural use of chlorpyrifos did not coincide with peak detection periods. None of the detected organochlorines is registered for agricultural use, although at the time, heptachlor was permitted for use as a domestic termiticide. Even in a semirural town with nearby widespread use of agricultural chemicals, community exposures to pesticides in ambient air may largely relate to their nonagricultural use.     

Pheochromocytoma and pregnancy: a case report and review of anesthetic management

PURPOSE: To describe a patient diagnosed with pheochromocytoma in the third trimester of pregnancy and discuss the perioperative and anesthetic management. CLINICAL FEATURES: A 32-yr-old previously healthy woman (gravida 4, para 2) presented to our tertiary care obstetrical hospital at 34 weeks five days gestation with a history of labile blood pressure and severe hypertension. A week prior to admission she began having episodes of severe headache, dizziness, sweating and nausea. On a routine obstetric visit she was noted to be severely hypertensive with a blood pressure of 200/120 mmHg. Biochemical investigations confirmed the diagnosis of pheochromocytoma and magnetic resonance imaging demonstrated a 3 cm x 3 cm right adrenal mass. The patient was invasively monitored in the intensive care unit and treated with alpha- followed by beta-blockade with phenoxybenzamine and metoprolol. A multidisciplinary conference was organized involving endocrinology, anesthesiology, general surgery and obstetrics to determine the most appropriate management of the patient. An uncomplicated laparoscopic adrenalectomy was performed following a period of recovery after an uneventful elective Cesarean delivery. CONCLUSIONS: The primary goals in the management of pheochromocytoma in pregnancy are early diagnosis, avoidance of a hypertensive crisis during delivery and definitive surgical treatment. Timing of surgical resection will depend on the gestational age at which diagnosis is made. Cesarean section is the preferred mode of delivery when the tumour is still present. This case illustrates that with antenatal diagnosis, advanced methods of tumour localization, adequate preoperative adrenergic blockade and team planning, pheochromocytoma in pregnancy can be treated successfully.