Short communication: Investigation of antibiotic alternatives to improve health and growth of veal calves.

The inherent disease susceptibility of veal calves results in frequent antimicrobial use. Improvements in antimicrobial stewardship necessitate alternative therapies to improve calf health and growth, while reducing the need for antimicrobials important to human health. This study investigated the effect of 2 alternative therapies, lactoferrin (an iron-binding protein found in colostrum) and cinnamaldehyde (an essential oil of the cinnamon plant) on growth, disease incidence, and mortality risk in special-fed veal calves. On the day of arrival to the growing facility (3 to 7 d of age), calves (n = 80 per treatment) were randomized to 1 of 3 treatments: (1) control (no supplement), (2) lactoferrin (1 g/d in milk replacer for 7 d), or (3) cinnamaldehyde (1 g/d in milk replacer for 21 d). Body weight was measured on the day of arrival (d 0), 21, and 42 d postarrival. Health assessments were performed twice weekly through 21 d, and mortality records were obtained through 6 wk postarrival. A repeated-measures ANOVA was used to compare growth between treatment groups, and a Poisson regression model (PROC GENMOD, SAS v. 9.4, SAS Institute Inc., Cary, NC) was used to test differences between groups in the incidence of diarrhea (fecal score ≥2 with and without depression and temperature) and disease through 3 wk postarrival. Body weight and average daily gain were similar between treatments. Neither lactoferrin nor cinnamaldehyde had an effect on diarrhea incidence. However, the risk of navel inflammation was significantly lower for calves that received cinnamaldehyde compared with calves in the control group. Mortality through 6 wk postarrival was low, with 4, 1, and 0 deaths from the control, lactoferrin, and cinnamaldehyde treatment groups, respectively. Additional research is needed to investigate various doses of these alternative therapies on calf health and growth, in addition to different routes of administration.

Veal calf health on the day of arrival at growers in Ohio.

Veal calves are at high risk for disease and mortality in early life. Calves face a number of stressors before arriving at the grower, including long transport times, which may contribute to poor health. Our objectives were to 1) estimate the prevalence of poor health outcomes in veal calves on arrival at growers in Ohio; 2) determine risk factors for health outcomes on arrival, including BW and auction site (spread across 5 states in the Northeastern United States); and 3) determine if health outcomes on arrival predict early mortality. A physical examination was conducted on approximately 30 calves (mean of 45.9 kg [SD 3.0]) from 12 cohorts ( = 383 calves). Exams included a blood sample to determine packed cell volume (an estimate of dehydration using a cutoff > 46%) and total protein (an estimate failure of passive transfer using a cutoff < 5.5 g/dL and 6.0 g/dL to account for dehydration). Diarrhea, respiratory disease, depression, navel inflammation, and a skin tent test (a second indicator of dehydration) were also recorded. Mortality within 4 wk of age was collected from farm records. Descriptive statistics were used to describe the prevalence of calves with poor health outcomes on arrival. Generalized linear mixed models were used to identify risk factors for poor health on arrival and assess if poor health increased the incidence risk of mortality. Upon arrival, 6% (95% confidence interval 4.4 to 7.6%) of calves had failure of passive transfer using a cut-off of 5.5 g/dL, and 22.5% (18.1 to 26.8%) had failure of passive transfer using a cut-off of 5.5 g/dL, and 22.5% (18.1 to 26.8%) had failure of passive transfer using a cut-off of 6.0%; 14% (9.1 to 18.8%) had diarrhea, 0.5% (0 to 1.3%) had respiratory disease, 14% (8.5 to 19.3%) were depressed, and 27% (22.7 to 30.7%) had inflamed navels. In addition, 35.1% (23.5 to 46.6%) of calves were dehydrated using a skin tent test, but only 1.3% (0.0 to 2.9%) were dehydrated based on the packed cell volume threshold. Auction site was associated with depression on arrival ( = 0.008) and tended to be associated with skin tent on arrival ( = 0.08). None of the health variables were predictors of early mortality; however, mortality was generally low for all cohorts (4.3%; range 1.7 to 6.8%). These results estimate the prevalence of dehydration, diarrhea, navel inflammation, and depression in veal calves on arrival at growers and demonstrate that some health outcomes are dependent on auction site. We conclude that there are many opportunities to intervene to improve their health and welfare before the calves arrive at the grower.

Bilateral glossopharyngeal neuropathy following chemo and radiation therapy for a primitive neuroectodermal tumour.

This case describes a young adult male patient diagnosed and treated for a primitive neuroectodermal tumour (PNET) at 3 years of age. Chemotherapy and radiation therapy used following surgical treatment of this tumour have known neurotoxic complications, some of which have delayed onset. In this case, the patient exhibited sudden onset, persistent bilateral and deep ear pain that was consistent with a neuropathy of the glossopharyngeal nerve occurring 17 years after the completion of therapy for PNET. Treatment with pregabalin was successful with near-complete resolution of the complaint. The diagnostic certainty in this case is discussed in relation to the current diagnostic criteria for neuropathic pain.

Renal tubular epithelial cell apoptosis by Fas-FasL-dependent self-injury can augment renal allograft injury.

The role of Fas-FasL interactions in kidney allograft injury may be complex as renal tubular epithelial cells (TEC) express both Fas and FasL. The role and regulation of TEC self-injury has not been investigated. In co-cultures of TEC, FasL-bearing, Fas-null TEC was demonstrated to induce apoptosis of TEC-bearing Fas. Co-culturing effector lpr-TEC (M3.1-lpr) with target WT-TEC (CS3.7) at a ratio of 10:1 (E/T) induced 15.2 +/- 2.4% of target apoptosis as compared to its basal level of 2.6 +/- 0.3%. Similarly lpr-TEC induced apoptosis in gld-TEC (MRM-gld) from a basal level of 3.7 +/- 0.2% to 6.4 +/- 0.3%. Expression of kidney Fas-FasL on injury was tested in a renal transplant model. C57BL/6 (B6) mice were transplanted with Fas-deficient C3H-lpr/lpr or FasL mutation C3H-gld/gld kidneys as compared to normal (wild-type [WT]) C3H/Hej donors. Survival of both lpr and gld recipient was improved compared to WT donors (P <.05) as was function of lpr and gld kidneys indicated by a lower serum creatinine (LPR: 41 +/- 8 micromol/L; GLD: 52 +/- 7 micromol/L) as compared to the WT donors (84 +/- 8 micromol/L, P <.001). These results demonstrate that activated TEC may commit a novel and previously unreported form of self-injury (fractricide) through Fas-FasL. These results suggest that inhibition of renal Fas or FasL might be a useful strategy to prevent TEC loss during rejection.

Influence of oocyte collection technique on initial chromatin configuration, meiotic competence, and male pronucleus formation after intracytoplasmic sperm injection (ICSI) of equine oocytes.

There is a great variability in the success of horse oocyte maturation and fertilization among laboratories. This study was conducted to determine if the meiotic and developmental competence of horse oocytes could be dependent on the method of oocyte collection, i.e., aspiration of follicular fluid with a vacuum apparatus, or opening follicles and scraping the granulosa layer. Horse oocytes were recovered from abattoir ovaries by aspiration or scraping and classified as having compact (Cp), expanded (Ex), or partial (P) cumuli. In Experiment 1 (Part A in May and Part B in October), oocytes were fixed immediately after collection to assess whether the collection method influenced the initial chromatin configuration of oocytes. In Experiment 2, in vitro maturation rates of oocytes recovered by aspiration or scraping were compared. In Experiment 3, oocytes were matured in vitro and submitted to intracytoplasmic sperm injection (ICSI). Initial chromatin configuration differed according to collection method in that there was a significantly higher prevalence of diffuse chromatin within the germinal vesicle in oocytes recovered by scraping than in oocytes recovered by aspiration (29/87, 33% and 28/166, 17%, respectively; P < 0.01). Maturation of oocytes to metaphase II did not significantly differ between scraped and aspirated oocytes (56/101, 55.4 % vs. 65/106, 61.4%, respectively). The overall pronucleus formation rate after ICSI of oocytes recovered by scraping was not significantly different than that of oocytes recovered by aspiration (50/99, 52.6% vs. 50/85, 68.5 %, respectively); however, the rate of abnormal fertilization was significantly higher for oocytes collected by aspiration (14/73, 19% vs. 6/94, 6%, respectively; P <0.05). These results demonstrate that the collection method affects the population of recovered oocytes and may contribute to differences in results observed among laboratories working with horse oocytes.

Maintaining a catalog of manually-indexed, clinically-oriented World Wide Web content.

With no quality controls and a highly distributed means of posting information, finding high-quality, clinically-oriented content on the World Wide Web can be difficult. Maintaining a catalog of such information can be equally challenging. CliniWeb is a catalog of quality-filtered and clinically-oriented content on the Web designed to enhance access to such information. This paper describes a group of semi-automated tools have been developed to maintain the CliniWeb database. One allows easier identification of content by utilizing Web crawling techniques from high-level pages. Another allows easier selection of content for inclusion and its indexing. A final one checks links to help keep the database current. These are augmented by general plans to adopt more detailed metadata and linkages into the medical literature.

Myelodysplastic and myeloproliferative disorders of childhood: a study of 167 patients.

Myelodysplastic syndromes (MDS) and myeloproliferative syndromes (MPS) of childhood are a heterogeneous group of clonal disorders of hematopoiesis with overlapping clinical features and inconsistent nomenclature. Although a number of genetic conditions have been associated with MDS and MPS, the overall contribution of inherited predispositions is uncertain. We report a retrospective study examining clinical features, genetic associations, and outcomes in 167 children with MDS and MPS. Of these patients, 48 had an associated constitutional disorder. One hundred one patients had adult-type myelodysplastic syndrome (A-MDS), 60 had juvenile myelomonocytic leukemia (JMML), and 6 infants with Down syndrome had a transient myeloproliferative syndrome (TMS). JMML was characterized by young age at onset and prominent hepatosplenomegaly, whereas patients with A-MDS were older and had little or no organomegaly. The most common cytogenetic abnormalities were monosomy 7 or del(7q) (53 cases); this was common both in patients with JMML and those with A-MDS. Leukemic transformation was observed in 32% of patients, usually within 2 years of diagnosis. Survival was 25% at 16 years. Favorable prognostic features at diagnosis included age less than 2 years and a hemoglobin F level of less than 10%. Older patients tended to present with an adult-type MDS that is accommodated within the French-American-British system. In contrast, infants and young children typically developed unique disorders with overlapping features of MDS and MPS. Although the type and intensity of therapy varied markedly in this study, the overall outcome was poor except in patients with TMS.

MLL genomic breakpoint distribution within the breakpoint cluster region in de novo leukemia in children.

PURPOSE: To assess translocation breakpoint distribution within the MLL genomic breakpoint cluster region (bcr), 40 cases of de novo leukemia in children were examined by karyotype and Southern blot analysis. PATIENTS AND METHODS: Criteria for inclusion were karyotypic or molecular rearrangement of chromosome band 11q23. Of the 40 cases, 31 occurred in infants. Twenty cases were acute lymphoblastic leukemia (ALL), 17 were acute myeloid leukemia (AML), and 3 were biphenotypic. RESULTS: Karyotype identified 27 cases with translocation of chromosome band 11q23 and 2 with abnormalities of band 11q13 but not 11q23. Southern blot analysis showed rearrangement within the MLL genomic bcr in 38 of the 40 cases. In these 38, additional probe-restriction digest combinations localized MLL genomic breakpoints to the 5' portion of the bcr in 14 cases and to the 3' portion in 18; material was insufficient for further localization to 5' or 3' within the bcr in 6 cases. In the two remaining cases, both with t(4;11)(q21;q23), one breakpoint mapped 5' of the bcr between intron 3 and exon 5, whereas the other breakpoint was neither within nor 5' of the MLL genomic bcr. CONCLUSIONS: Suggested trends warranting investigation in more patients were breakpoint sites in the 3' bcr in AML and in patients older than 12 months. The distribution of MLL genomic breakpoints within the bcr in de novo leukemia in children is distinct from that in adults, where the breakpoints cluster in the 5' portion of the bcr.

RAS mutations in pediatric leukemias with MLL gene rearrangements.

Translocations of the MLL gene at chromosome band 11q23 are the most common cytogenetic alterations in de novo leukemia in infants and in leukemia related to chemotherapy with DNA topoisomerase II inhibitors. Experiments on knock-in mice suggest that additional mutational events may by required for full leukemogenesis. Therefore, we used single-strand conformation polymorphism analysis and an allele-specific restriction enzyme assay to investigate the frequency of KRAS and NRAS mutations in 32 pediatric leukemias with translocation of the MLL gene. Of 25 de novo cases, 13 were acute lymphoblastic leukemia (ALL), 10 were acute myeloid leukemia (AML), and 2 were biphenotypic. Three secondary leukemias were AML, 1 was biphenotypic, 1 was ALL, and 2 were diagnosed as myelodysplasia. The frequency of RAS mutations was 2 of 10 in de novo AML. Both mutations occurred in infant monoblastic variants. RAS mutations were otherwise absent in this series. This is the first report of congenital leukemias where translocation of the MLL gene and RAS mutation coexist. The frequency of RAS mutations in de novo AMLs with MLL gene translocations is similar to that in other forms of AML, but RAS mutations play a limited role in lymphoid and treatment-related leukemias with similar translocations.

New approaches to syphilis control. Finding opportunities for syphilis treatment and congenital syphilis prevention in a women's correctional setting.

BACKGROUND: With prostitution and drugs the most common reasons for arrest among New York City (NYC) women, female arrestees are at high risk for acquiring syphilis and delivering congenitally infected babies. Despite routine syphilis screening of all NYC inmates, many are released before the need for treatment is recognized, and once released, few could be found for treatment. GOALS: To improve syphilis treatment rates among female correctional inmates in NYC. STUDY DESIGN: At a women's correctional health clinic, on-site, rapid, qualitative nontreponemal syphilis testing (STAT rapid plasma reagin [RPR]) and on-line access to the local syphilis case registry were introduced to supplement the usual admission medical evaluation. Treatment decisions made using the authors' jail protocol were compared with treatment criteria used in NYC's sexually transmitted disease (STD) clinics. Patients consisted of a consecutive sample of 685 remandees admitted one or more times during the day shift, March 24, 1993, to July 31, 1993, who had a full complement of mandatory admission medical tests. Using the study protocol, syphilis treatment decisions were made and needed treatment was furnished at the end of the admission medical evaluation. The main outcome measures were correct identification and treatment of syphilis in this population, compared with standard NYC Department of Health (DOH) STD clinic practice, as well as the effect of the jail protocol on pregnancy outcomes and need to treat offspring for congenital syphilis. RESULTS: Compared with NYC DOH STD clinic practice, the study protocol was 95% sensitive and 88% specific in arriving at appropriate treatment for syphilis. Treatment at the end of the admission medical evaluation increased syphilis treatment rates from 7% to 84% of women with indications for treatment and to 88% of pregnant women with indications for treatment. Prospective follow-up for birth outcomes revealed no spontaneous abortions and eight live births. Seven of the eight did not need congenital syphilis treatment because their mothers were adequately treated while incarcerated. CONCLUSIONS: Qualitative (or STAT) RPR testing and access to DOH syphilis case registry data provide prompt and accurate diagnostic information that can lead to an overall increase in the number of inmates appropriately treated (with a minimum amoung of overtreatment) in a women's correctional facility. This protocol may be applicable in other high-risk, transient populations.

Controlled clinical laboratory comparison of BACTEC plus aerobic/F resin medium with BacT/Alert aerobic FAN medium for detection of bacteremia and fungemia.

Blood specimens collected from adult patients with suspected sepsis in four medical centers were inoculated into BACTEC Plus/F and BacT/Alert FAN aerobic culture bottles. Both bottles of 7,401 bottle pairs contained the prescribed blood volume of 8 to 12 ml. Bottles were incubated in their respective instruments for a standard 7-day protocol or until the instruments signaled that they were positive. A total of 720 isolates that were judged to represent true infections were recovered from 338 patients; 451 isolates were recovered from both bottles, 143 were recovered from only the Plus/F bottle, and 126 were recovered from only the FAN bottle (P was not significant). Although more Histoplasma capsulatum isolates were recovered from Plus/F bottles (P < 0.005), there were no other statistically significant differences in recovery rates of individual species or groups of organisms between the two systems. Of 329 monomicrobic patient septic episodes, 244 episodes were detected by both blood culture systems, 40 were detected only by the BACTEC system, and 45 were detected only by the BacT/Alert system (P was not significant). There was no significant difference between the two systems in the detection of septic episodes among patients receiving antibiotic therapy at the time of blood cultures. Of the cultures found to be positive within the first 72 h of incubation, detection was on average earlier by the BACTEC system (16.9 h) than by the BacT/Alert system (18.7 h). Larger differences in average time to detection were seen with streptococci (10.7 h by the BACTEC system and 17.9 h by the BacT/Alert system) and yeasts (an average of 29.4 h by the BacT/Alert system versus 37.2 h by the BACTEC system). With the exception of the differences noted above, BACTEC Plus/F aerobic resin and BacT/Alert aerobic FAN blood culture bottles were comparable in their abilities to recover aerobic and facultative organisms.

Clonal expansion of germline B-lineage acute lymphoblastic leukemia in severe combined immunodeficient mice.

CD19+ B lineage acute lymphoblastic leukemias (ALLs) with unrearranged Ig and TCR genes are designated germline B lineage ALLs. We used CDR3 PCR to determine whether pediatric germline B lineage ALLs contain minor subclones with rearranged Ig H V genes. In six of seven cases there were no PCR detectable CDR3 rearrangements. One case with a smear pattern on CDR3 PCR contained multiple unique CDR3 sequences at frequencies of 1-2 per 2,600, suggesting that polyclonal B cells were present at low frequency. To verify that the germline patterns were from leukemic cells and evaluate in vivo subclone differentiation, a germline B lineage ALL with the t(4;11) translocation was propagated in severe combined immunodeficient SCID) mice. The Ig and TCR genes in the leukemic cells recovered from mouse tissues were germline by Southern blot analysis except for single rearrangements that suggested subclone evolution at the Ig H and lambda loci in addition to the germline population. No CDR3 sequences were detected, indicating that the observed Ig H gene rearrangement most likely was a DJ joining. This study suggests that the transformed cell in germline B lineage ALL represents an early pro-B cell with limited tendency to further differentiate.

Beam characteristics of a new generation 50 MeV racetrack microtron.

The first of a new generation of microtron accelerators has been installed and tested. It is currently in use for multisegment conformal radiotherapy at our institution. The unit produces x rays and electrons from 10 to 50 MeV in 5 MeV increments. It incorporates a 64 leaf, doubly focused multileaf collimator (MLC), which can be used to shape x-ray and electron beams. Both x-ray and electron beams are produced by magnetically scanning the electron beams from the accelerator. The new generation unit incorporates a purging magnet to sweep away any primary or secondary electrons that pass through the target(s). In this paper, the beam characteristics of the accelerator that were studied during acceptance testing are described. Representative examples of depth doses, beam profiles, output factors, and elementary beam distributions are presented and discussed, in comparison with the earlier generation of microtron accelerators and with other radiotherapy machines.

ALL-1 gene rearrangements in DNA topoisomerase II inhibitor-related leukemia in children.

We examined clinical, morphologic, and cytogenetic features and ALL-1 (MLL, Htrxl, HRX) gene rearrangements in 17 cases of secondary leukemia that occurred 11 months to 9 years from diagnoses of primary cancers in children who received topoisomerase II inhibitors or developed secondary leukemias typical of those associated with this therapy. Primary diagnoses included nine solid tumors and eight leukemias. Ten secondary leukemias were acute myeloid leukemia (AML), one was of mixed lineage, two were acute lymphoblastic leukemia (ALL), and four presented as myelodysplasia. Of 15 cases with 11q23 involvement, 11 (73%) were cytogenetically identifiable; four cases had molecular rearrangement only. By Southern blot, rearrangements within the ALL-1 gene were similar to sporadic cases. The results of this analysis suggest the following: (1) In most pediatric cases of topoisomerase II inhibitor-associated leukemia, there is disruption of the breakpoint cluster region of the ALL-1 gene at chromosomal band 11q23. (2) Exposure histories vary in secondary 11q23 leukemia, as the only topoisomerase II inhibitor was dactinomycin in one case, and, in another case, no topoisomerase II inhibitor was administered. (3) There is clinical, morphologic, cytogenetic, and molecular heterogeneity in pediatric secondary 11q23 leukemia. (4) There are some survivors of pediatric secondary 11q23 leukemia, but the outcome is most often fatal.

Calculated and TLD-based absorbed dose estimates for I-131-labeled 3F8 monoclonal antibody in a human neuroblastoma xenograft nude mouse model.

Preclinical evaluation of the therapeutic potential of radiolabeled antibodies is commonly performed in a xenografted nude mouse model. To assess therapeutic efficacy it is important to estimate the absorbed dose to the tumor and normal tissues of the nude mouse. The current study was designed to accurately measure radiation does to human neuroblastoma xenografts and normal organs in nude mice treated with I-131-labeled 3F8 monoclonal antibody (MoAb) against disialoganglioside GD2 antigen. Absorbed dose estimates were obtained using two different approaches: (1) measurement with teflon-imbedded CaSO4:Dy mini-thermoluminescent dosimeters (TLDs) and (2) calculations using mouse S-factors. The calculated total dose to tumor one week after i.v. injection of the 50 microCi I-131-3F8 MoAb was 604 cGy. The corresponding decay corrected and not corrected TLD measurements were 109 +/- 9 and 48.7 +/- 3.4 cGy respectively. The calculated to TLD-derived dose ratios for tumor ranged from 6.1 at 24 h to 5.5 at 1 week. The light output fading rate was found to depend upon the tissue type within which the TLDs were implanted. The decay rate in tumor, muscle, subcutaneous tissue and in vitro, were 9.5, 5.0, 3.7 and 0.67% per day, respectively. We have demonstrated that the type of tissue in which the TLD was implanted strongly influenced the in vivo decay of light output. Even with decay correction, a significant discrepancy was observed between MIRD-based calculated and CaSO4:Dy mini-TLD measured absorbed doses. Batch dependence, pH of the tumor or other variables associated with TLDs which are not as yet well known may account for this discrepancy.

Replacement therapy with a monoclonal antibody purified protein C concentrate in newborns with severe congenital protein C deficiency.

Protein C replacement therapy with a monoclonal antibody purified, virus inactivated protein C concentrate was carried out in nine infants (three male, six female) with severe congenital protein C deficiency and life-threatening purpura fulminans and/or thrombosis associated with disseminated intravascular coagulation (DIC). Eight infants were homozygous for protein C deficiency; one was a compound heterozygote. The treatment period varied from 22 days to three years. The half-life of protein C was found to be as short as two to three hours during activation of the coagulation system, increasing to approximately ten hours after stabilization. During the acute phase, protein C levels of 0.10 to 0.25 IU/mL were associated with elevated markers of coagulation activation indicating DIC, while protein C levels greater than 0.25 were associated with normalization of coagulation markers. No product-related side effects were reported. Episodes of bleeding or purpura recurred in all patients who were switched to oral anticoagulant therapy, necessitating reinstatement of protein C replacement therapy, either as needed to control symptoms, or on a long-term prophylactic schedule, alone or in addition to oral anticoagulation. Home treatment with protein C concentrate allowed a near-normal life-style for patients who otherwise would be hospitalized for long periods of time.

Initial clinical experience with computer-controlled conformal radiotherapy of the prostate using a 50-MeV medical microtron.

PURPOSE: We have described previously a model for delivering computer-controlled radiation treatments. We report here on the implementation and first year's clinical experience with such treatments using a 50 MeV medical microtron. METHODS AND MATERIALS: The microtron is equipped with a multileaf collimator and is capable of setting up and treating a sequence of fixed fields called segments, under computer control. An external computer derives machine parameters for the segments from a three-dimensional treatment planning system, transfers them to the microtron control computer, checks the machine settings before allowing dose delivery to begin, and records the treatment. We describe the patient treatment methodology, portal film acquisition, electronic portal imaging, and quality assurance. RESULTS: Patient treatments began in July 1992, comprising six-segment conformal treatments of the prostate. Using the recorded treatment data, the system performance has been examined and compared to other treatment machines. The average treatment time is 10 min, of which 4 min is for computer-controlled setup and irradiation; the remaining time is for patient positioning and checking of clearances. Long-term reproducibility of computer-controlled setup of the gantry and multileaf position is better than 0.5 degrees and 1 mm, respectively. Termination due to a machine fault has occurred in 5.5% of treatments, improving to 2.5% in recent months. CONCLUSION: Our initial experience indicates that computer-controlled segmental therapy can be performed reliably on a routine basis. Treatment times with the microtron are significantly shorter than with conventional linacs, and setup accuracy is consistent with that needed for conformal therapy. We believe that treatment times can be further improved through software upgrades and integration of electronic portal imaging.

Bone marrow transplantation in Fanconi anemia using matched sibling donors.

Eighteen patients with Fanconi anemia (FA) with evidence of bone marrow (BM) aplasia underwent allogenic BM transplants (BMT) from matched sibling donors (MSD). Median age at BMT was 7.6 years. Conditioning consisted of low-dose cyclophosphamide (CY; 5 mg/kg x 4 days) and thoracoabdominal irradiation (TAI; 400 cGy). Graft-versus-host disease (GVHD) prophylaxis included cyclosporin A and prednisone. In addition antithymocyte globulin (ATG) was administered in the pretransplant period to promote engraftment and in the posttransplant period for additional GVHD prophylaxis. Engraftment occurred rapidly (median, 12 days for an absolute neutrophil count > or = 0.5 x 10(9)/L; median, 22 days for platelet count > or = 50 x 10(9)/L). Seventeen patients have sustained engraftment and are transfusion-independent, with Lansky scores of 100% at median follow-up of 27 months. One patient developed graft failure 4 months after initial engraftment and required a second BM infusion. None of the patients developed acute GVHD; 3 patients (16%) developed chronic GVHD. BMT is a feasible option for FA patients having an MSD and should be performed at a young age and early in the course of the disease, before the development of complications. We believe the addition of ATG to the transplant regimen of low-dose CY, TAI, and cyclosporin was responsible for improvement in the survival of FA patients undergoing BMT. The regimen was well tolerated and was associated with a low incidence of complications including GVHD.

Detection of unexpected clones of monosomy 7 in childhood acute lymphoblastic leukemia using fluorescence in situ hybridization.

The feasibility of a fluorescence in situ hybridization (FISH) technique for the detection of leukemic clones with masked chromosomal aberration in interphase nuclei was tested in childhood acute lymphoblastic leukemia (ALL). Twenty-one cases of ALL previously studied by classical metaphase cytogenetics were retrospectively analysed using a centromere-specific chromosome 7 probe. Five cases with karyotypic abnormalities of chromosome 7 (2 with trisomy 7, 2 with monosomy 7 and 1 with trisomy & tetrasomy 7) showed a correlation with FISH results, whereas in five other cases monosomy 7 was found in 12-43% of cells only by FISH. The unexpected detection of monosomy 7 in these latter ALL patients suggests that either these clones are quiescent or unable to enter mitosis in vitro. This suggests that FISH and metaphase cytogenetics must be combined whenever possible to obtain comprehensive karyotypic information.

Preclinical evaluation of the reliability of a 50 MeV racetrack microtron.

PURPOSE: A 50 MeV racetrack microtron has been installed and tested at Memorial Sloan-Kettering Cancer Center. It is designed to execute multi-segment conformal therapy automatically under computer control using scanned X ray and electron beams from 10 to 50 MeV. Prior to acceptance of the machine from the manufacturer, formal reliability testing was carried out. Only in this way could confidence be gained in its usefulness for routine 3D computer-controlled conformal therapy. MATERIALS AND METHODS: To assess reliability, a set of 25 multi-segment test cases, each consisting of 10 to 17 fixed segments, was developed. The field arrangements and modalities for some of the test cases were identical to 3D conformal treatments that were being delivered with multiple static fields on conventional linear accelerators at our institution. Other cases were designed to explore reliability under more complex sets of conditions. These cases were "treated" repeatedly during a total period of 45 hours, over 5 days. During the treatments, ion chambers attached to the head of the machine provided dosimetric data for each field. Data from sensors connected to every set-up parameter (for example, couch positions, gantry angle, collimator leaf positions, etc.) were recorded and verified by an external computer. RESULTS: While preliminary tests indicated an interlock rate of 5%, final reliability test results demonstrated an interlock fault rate of approximately 0.5%. The reproducibility of dosimetric data and geometric setup parameters was within specifications. As an example, leaf position reproducibility in the patient plane was within 0.5 mm for 97% of the setups. The times required to carry out treatments were recorded and compared with the times to carry out identical treatments on a conventional linear accelerator with cerrobend blocks. Areas where additional time savings can be achieved were identified. CONCLUSIONS: As an integral part of acceptance testing, the Scanditronix MM50 was rigorously tested for reliability. The machine successfully passed these tests, providing increased confidence in its usefulness for routine 3D conformal therapy.