Frequent ongoing T-cell receptor rearrangements in childhood B- precursor acute lymphoblastic leukemia: implications for monitoring minimal residual disease

Crosslineage T-cell receptor delta (TCR delta) rearrangements are widely used as tumor markers for the follow up of minimal residual disease in childhood B-precursor acute lymphoblastic leukemia (ALL) by polymerase chain reaction (PCR). The major drawback of this approach is the risk of false-negative results due to clonal evolution. We investigated the stability of V delta 2D delta 3 rearrangements in a group of 56 childhood B-precursor ALL patients by PCR and Southern blot analysis. At the PCR level, V delta 2D delta 3-to-J alpha rearranged subclones (one pathway for secondary TCR delta recombination) were demonstrated in 85.2% of V delta 2D delta 3-positive patients tested, which showed that small subclones are present in the large majority of patients despite apparently monoclonal TCR delta Southern blot patterns. Sequence analysis of V delta 2D delta 3J alpha rearrangements showed a biased J alpha gene usage, with HAPO5 and J alpha F in 26 of 32 and 6 of 32 clones, respectively. Comparison of V delta 2D delta 3 rearrangement status between diagnosis and first relapse showed differences in seven of eight patients studied. In contrast, from first relapse onward, no clonal changes were observed in six patients studied. To investigate the occurrence of crosslineage TCR delta rearrangements in normal B and T cells, fluorescence-activated cell sorter-sorted peripheral blood CD19+/CD3- and CD19-/CD3+ cell populations from three healthy donors were analyzed. V delta 2D delta 3 rearrangements were detected at low frequencies in both B and T cells, which suggests that V delta 2-to-D delta 3 joining also occurs during normal B-cell differentiation. A model for crosslineage TCR delta rearrangements in B-precursor ALL is deduced that explains the observed clonal changes between diagnosis and relapse and is compatible with multistep leukemogenesis of B-precursor ALL.     

A SURVEY OF CONCURRENT DRUG THERAPY AMONG DAY UNIT PATIENTS

SUMMARY In order to assess the reliability of drug information supplied by day-stay cases, 85 consecutive patients were interviewed. A comparison of the interview answers with the details previously volunteered during the admission procedure showed an increase of 80% in the information given by the patient. While the detailed interviewing technique is time-consuming and may not be infallible, this substantial increase in information highlights problems in the current routine.     

Laparoscopic bile duct injuries. Risk factors, recognition, and repair.

Records of 11 patients undergoing biliary reconstruction after laparoscopic cholecystectomy are reviewed. Ductal injuries resulted from failure to define the anatomy of Calot's triangle. Risk factors include scarring, acute cholecystitis, and obesity. Presenting findings included anorexia, ileus, failure to thrive, pain, ascites, and jaundice. All patients required hepaticojejunostomies, which were multiple and above the hepatic bifurcation in four patients. Given the extensive nature of these injuries and the frequent need for intrahepatic anastomosis and early stenosis of repairs by referring physicians, we recommend reconstruction be undertaken by an experienced hepatobiliary surgeon. To avoid injuries, a greater appreciation of risk factors and anatomic distortion and variance and strict adherence to principles of dissection and identification of anatomic structures are suggested. The use of cholangiography and a low threshold for conversion to the open procedure are advised.     

Nicotine discrimination and self-administration in humans as a function of smoking status

Nicotine’s discriminative stimulus effects may be critical to understanding reinforcement of tobacco smoking. It is not known whether regular nicotine exposure produces tolerance or sensitivity to these effects. In this study, male and female smokers (n = 11) and never-smokers (n = 10) were trained to discriminate 20 μg/kg nicotine by nasal spray from placebo (0) on day 1. On day 2, both groups were tested on generalization of this discrimination across intermittent presentations of 0, 3, 6, 12, and 20 μg/kg nicotine in random order. Quantitative and quantal behavioral discrimination tasks, used in previous research, were employed. On day 3, subjects were instructed to self-administer sprays from the 20 μg/kg nicotine versus 0 bottles in a concurrent-choice procedure. All but one subject (female smoker) learned reliably to discriminate 20 μg/kg nicotine from placebo (≥ 80% correct) on day 1. Nicotine-appropriate responding on day 2 was attenuated in smokers versus never-smokers at 20 μg/kg on the quantitative task and at 12 μg/kg on the quantal task, suggesting tolerance. There was no difference in responding at other doses. Smokers also showed attenuated responses on the subjective measure of “head rush”, which was associated with discrimination responding in both groups. Nicotine self-administration was significantly greater in smokers versus never-smokers, who self-administered nicotine below chance levels, and was inversely related to discrimination behavior in never-smokers but unrelated in smokers. Women smokers showed less change in nicotine-appropriate responding across generalization doses, reported less confidence in discriminating training doses during acquisition on day 1, and tended to self-administer less nicotine on day 3. These results indicate that smokers may become tolerant to the discriminative stimulus effects of nicotine, perhaps promoting increased use. Received: 1 October 1996/Final version: 28 January 1997     

Long-term effects of bone marrow transplantation

As increasing numbers of children are surviving beyond the 1st decade after marrow transplantation and increasing numbers of children are receiving marrow transplants each year, the delayed effects related to the transplant procedure itself, the original disease, and/or the transplant preparative regimen are becoming apparent. Late effects related to the transplant procedure include those of engraftment stability, the chronic immunosuppression of chronic graft-versus-host disease and delayed immunologic recovery. Recurrent disease is the major late effect related to the patient's original disease. The late effects which may be related to previous therapy administered and/or the transplant preparative regimen include abnormalities of neuroendocrine function, ocular problems, dental developmental abnormalities in young children, central nervous system dysfunction and the development of secondary malignancies. To improve the quality of life of marrow transplant recipients and to prevent some of the growth and development abnormalities which may occur, an awareness of the problems encountered to date is needed.     

Screening for sexually transmitted diseases during preparticipation sports examination of high school adolescents.

In an urban school district, 636 students in grades 9-12 were tested for Chlamydia trachomatis and Neisseria gonorrhoeae by ligase chain reaction assays using specimens collected for routine urinalyses during sports physical examinations. Chlamydia and gonorrhea prevalences were 2.8% and 0.7% among males, and 6.5% and 2.0% among females, respectively. Among athletes infected with either sexually transmitted disease (STD), 93.1% reported no symptoms, and treatment was documented for 75.9%. Sports physicals offered a unique opportunity to screen and treat adolescents for STDs and to provide STD-prevention counseling.     

Clinical importance of inducible beta-lactamases in gram-negative bacteria

The clinical problems caused by inducible beta-lactamases in certain gram-negative bacteria are being recognized with increasing frequency. These problems include the rapid emergence of multiple beta-lactam resistance during therapy with many of the newer beta-lactam antibiotics. Such multiply resistant organisms are now spreading within the hospital and have become important nosocomial pathogens. This has been a particularly difficult problem for intensive care units, cystic fibrosis centers and burn units where there are clusters of patients who are highly susceptible to infections with organisms likeEnterobacter spp.,Serratia spp. andPseudomonas aeruginosa, which possess inducible beta-lactamases. Only through an awareness of these problems, their cause, and restriction of the use of certain newer betalactam antibiotics can these problems be controlled.