Selective preparation of the [3,5-tBu2-1,2,4-C2P3]- ion and synthesis and structure of the cationic species nido-[3,5-tBu2-1,2,4-C2P3]+, isoelectronic with [C5R5]+.
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Journal Article↗
Biomedical subjects
Michael Green
Publications and source records attributed to Michael Green.
Posttransplantation lymphoproliferative disorders.
Over the last decade, much has been learned about the nature of PTLD. The pivotal role of EBV infection in most cases has been established, and the pathologic description of lesions has been simplified in the current classification. It seems likely that further understanding of the molecular pathology may lead to greater ability to define optimal treatment regimens and prognosis. Quantitative PCR techniques for EBV have enhanced the capability for early diagnosis of EBV infection and PTLD and have proved useful tools for monitoring response to therapy. In particular, this technique seems to help predict when reintroduction of immunosuppression should be instituted. Several exciting new therapies are on the horizon, including use of monoclonal antibodies against B-cell surface antigens and the development of cellular therapies, such as the use of EBV-specific cytotoxic T-cell infusions. Such strategies offer the promise of controlling abnormal B-cell proliferation without the risk of allograft rejection, because the host alloresponse is not enhanced by these therapies. The role of chemotherapy and the optimal regimens required remain to be defined fully. Understanding of the cause, behavior, and optimal treatment for EBV-negative PTLD remains limited, partly because of the rarity of these lesions. There is an increasing level of interest in PTLD among clinical and basic investigators and recognition of the need for multicenter trials to define optimal prevention and treatment strategies. A degree of optimism seems warranted.
Antiviral Agents↗
Lymphocyte subsets may discern treatment effects in children and young adults with post-transplant lymphoproliferative disorder.
To identify potential alternatives to Epstein-Barr virus (EBV)-specific cytotoxic T-cell responses, peripheral lymphocyte subsets (PLS) (CD4+, CD8+, CD3+, CD19+, CD56+) were measured by flow cytometry in children with abdominal transplants (n = 22) and heart transplants (n = 2), with (n = 14) and without (n = 10, group C) post-transplant lymphoproliferative disorder (PTLD). PTLD resolved with reduced immunosuppression and antiviral therapy in eight children (group B). Recalcitrant PTLD was observed in six children (group A). Recalcitrant PTLD followed prior antilymphocyte therapy [monoclonal anti-CD3 antibody (OKT3) and thymoglobin (n = 3) and thymoglobin (n = 1)] for refractory rejection in four of these six children, and resolved after treatment with rituximab (anti-CD20 monoclonal antibody). Ten children without PTLD served as a control group (group C). Between group comparisons showed a numeric increase in CD8 + cells and significantly lower CD4:CD8 ratios in both PTLD groups (A and B) compared with group C. Group A children also demonstrated significant depletion of natural killer (NK) cells, and post-rituximab depletion of B-cells compared with group B (no rituximab treatment). We conclude that NK cell depletion with a reversed CD4:CD8 ratio may represent a persistent immunosuppressed state, which may result from prior antilymphocyte therapy and may predispose to recalcitrant EBV-PTLD. Clinical remission with rituximab is accompanied by B-cell depletion. Serial monitoring of PLS from the time of diagnosis of PTLD will be necessary to confirm these observations.
Adolescent↗
Organ donation from children with meningitis.
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Adolescent↗
Infanticide in Malaysia: two case reports and a review of literature.
In a strict and conservative society like Malaysia, the number of cases of infanticide has continued to occur. The authors present two typical cases of infanticide in Malaysia. Case 1 concerned a body of a fully mature newborn fetus disposed in a rubbish bin. The head was traumatically amputated by the rubbish truck's compactor. The umbilical cord was still attached to the body, with no reddening around the insertion. The severed neck showed features consistent with post-mortem amputation. The significant finding was expanded crepitant lungs, which floated in water. The histology of the lungs showed expanded alveoli. It was concluded that the baby had been born alive, but no cause of death could be elicited. Case 2 concerned a decomposed mature newborn found in a scrub forest. The internal organs showed advanced putrefaction, the lungs being collapsed, congested, and hemorrhagic, typical of decomposed lungs. No conclusion could be made about the state of birth or the cause of death because of the putrefied state of the body. The two cases illustrate the typical cases and problems faced by pathologists locally and probably elsewhere in the world. Most of the bodies are found in a putrefied state. Pathologists have to ascertain not only maturity and live birth but also the cause of death, which may be very subtle or masked by putrefaction. The problems of diagnosis of live birth are discussed.
Amputation, Traumatic↗
Measurement of Epstein-Barr virus DNA loads in whole blood and plasma by TaqMan PCR and in peripheral blood lymphocytes by competitive PCR.
Epstein-Barr virus (EBV) DNA load values were measured in samples of whole blood (n = 60) and plasma (n = 59) by TaqMan PCR and in samples of peripheral blood lymphocytes (PBLs) (n = 60) by competitive PCR (cPCR). The samples were obtained from 44 transplant recipients. The whole-blood and PBL loads correlated highly (r(2) > 0.900), whereas the plasma and PBL loads correlated poorly (r(2) = 0.512). Testing of whole blood by TaqMan PCR is an acceptable alternative to testing of PBLs by cPCR for quantifying EBV DNA load.
DNA, Viral↗
Methamphetamine dependence is associated with neurocognitive impairment in the initial phases of abstinence.
This study documented the association between neurocognitive impairment and methamphetamine dependence in a sample of 27 methamphetamine-dependent individuals who achieved 5 to 14 days of continuously monitored abstinence and in 18 control subjects. Methamphetamine-dependent individuals performed significantly worse than control subjects on neurocognitive measures sensitive to attention/psychomotor speed, on measures of verbal learning and memory, and on executive systems measures sensitive to fluency. These findings are the first to demonstrate that methamphetamine dependence is associated with impairments across a range of neurocognitive domains in a sample of users whose abstinence was continuously monitored with the use of urine screening.
Adult↗
Chloroquine-resistant Plasmodium vivax malaria in Peru.
Reports from several sites in South America suggest the presence of isolated cases of chloroquine-resistant Plasmodium vivax malaria. To investigate the possibility of chloroquine-resistant P. vivax in Peru, we conducted 28-day in vivo drug efficacy trials at three sites in the Amazon region and one site on the northern Pacific Coast between 1998 and 2001. A total of 242 patients between the ages of 2 and 60 years were enrolled (177 from the Amazon region and 65 from the northern coast). All subjects received directly observed therapy with chloroquine, 25 mg/kg, over a three-day period. On enrollment, 49% had a documented fever and 96% had a history of fever; their geometric mean parasite density was 5,129 parasites/microL. A total of 212 (88%) of the 242 subjects completed their 28-day follow-up. Four of the 177 patients from the Amazon region had a recurrence of P. vivax parasitemia on days 21 and 28 after treatment was initiated. Two of these patients had chloroquine-resistant infections, based on polymerase chain reaction-single-stranded conformational polymorphism genotyping and chloroquine-desethylchloroquine blood levels, which were > or = 97 ng/mL at the time of the reappearance of parasitemia. None of the subjects studied on the northern Pacific Coast had recurrent parasitemia.
Adolescent↗
Causes of mortality beyond 1 year after primary pediatric liver transplant under tacrolimus.
BACKGROUND: Success of pediatric liver transplantation has improved significantly. Most posttransplant deaths occur early and are related to surgical complications or recipient status at the time of transplantation. The causes of mortality beyond the first year have not been well described. METHODS: Three hundred twenty-six pediatric liver transplants were performed between November 1989 and April 1998 using tacrolimus-based immunosuppression. Patients were followed until March 2002. Mean follow-up was 9.2+/-2.4 years. RESULTS: At 1 year, 279 patients (85.5%) were alive. In the subsequent 12.5 years, 10 of the remaining children died (3.58%) at a mean interval of 3.68+/-1.69 years after transplant. The mean age at transplant was 5.62+/-6.3 years. Six patients had infections as a major contributor to mortality, including two patients with posttransplant lymphoproliferative disorder (PTLD) and one patient that died after retransplantation for hepatitis. Two patients had recurrent malignancy. Other deaths were attributable to chronic rejection, liver failure after being lost to follow-up, and complications of cystic fibrosis. CONCLUSIONS: Pediatric liver transplantation using tacrolimus-based immunosuppression has demonstrated excellent success, with 1- and 10-year survival rates of 85.5% and 82.9%, respectively. Late mortality after pediatric liver transplantation overall remains low, with a rate of 0.32% per year. The most common cause of death was infection (60%), including PTLD-related disease (20%). However, in the recent cohort of patients who underwent transplantation after September 1995, there were no fatal cases of Epstein-Barr virus or PTLD or late mortality thus far, suggesting a benefit from improved infectious disease surveillance using currently available modalities. Mortality from chronic rejection and noncompliance under tacrolimus has been exceedingly rare.
Cause of Death↗
Ligand exchange reactions within the coordination sphere of a molybdenum eta 2(4e)-alkyne complex: the formation of an indole in a cascade reaction involving an alkyne and isonitrile ligands.
The exchange of phosphorus-containing ligands within the coordination sphere of molybdenum alkyne complexes is shown to be facile, a similar reaction with CNxyl (xyl = C6H3Me(2)-2,5) results in a remarkable coupling between the alkyne and three isonitrile ligands and C-H bond activation.
Journal Article↗
4alpha-Phorbol negates the inhibitory effects of phorbol-12-myristate-13-acetate on human cilia and alters the phosphorylation of PKC.
In medium 199, ciliary beat frequency (CBF) in human nasal epithelium declines to 60% of baseline by 2 h and 1 nM phorbol-12-myristate-13-acetate (PMA) doubles the rate of decline by activating protein kinase C (PKC). We find that a reported negative control for PMA, 4alpha-phorbol (1 pM-1 nM)+/-1 nM PMA, not only maintains CBF at baseline, but arrests a pre-existing PMA-induced decline in CBF and alters the profile of multiple phosphorylated PKC species. Thus, 4alpha-phorbol not only potently prevents PMA from inhibiting CBF but also has potent effects on the phosphorylation of PKC.
Blotting, Western↗
Erythromycin-resistant group A streptococci in schoolchildren in Pittsburgh.
BACKGROUND: Resistance to erythromycin has been very uncommon among group A streptococci in the United States. METHODS: As part of a longitudinal study, we obtained surveillance throat cultures twice monthly and with each new respiratory tract illness from children in kindergarten through grade 8 at one school in Pittsburgh. Screening for resistance to erythromycin and clindamycin was initially accomplished with use of the Kirby-Bauer disk-diffusion test. The minimal inhibitory concentration of resistant isolates was determined by the E test. A double disk-diffusion test was used to characterize the resistance phenotype, and the polymerase-chain-reaction assay was used to identify the resistance gene. The molecular relatedness of strains was determined by field-inversion gel electrophoresis. RESULTS: A total of 1794 throat cultures were obtained from 100 children between October 2000 and May 2001, of which 318 cultures (18 percent) from 60 of the children were positive for group A streptococci. Forty-eight percent of these isolates (153 of 318) were resistant to erythromycin. None were resistant to clindamycin. Results of the double disk-diffusion test indicated the presence of the M phenotype of erythromycin resistance. Molecular typing indicated that the outbreak was due to a single strain of group A streptococci. Of 100 randomly selected isolates of group A streptococci obtained from the community between April and June 2001, 38 were resistant to erythromycin. CONCLUSIONS: In January 2001, during a longitudinal study of schoolchildren, we detected the emergence of erythromycin resistance in pharyngeal isolates of group A streptococci. This clonal outbreak also affected the wider community.
Adolescent↗
Development of pancytopenia with neutralizing antibodies to thrombopoietin after multicycle chemotherapy supported by megakaryocyte growth and development factor.
Clinical trials of thrombopoietin (TPO), the central regulator of megakaryocytopoiesis, have revealed few side effects associated with its use. We here report a case of pancytopenia associated with the development of neutralizing antibodies to TPO that occurred in a patient who had undergone multicycle chemotherapy with multiple cycles of subcutaneous administration of pegylated recombinant human megakaryocyte growth and development factor. Samples of the patient's bone marrow showed trilineage hypoplasia with absence of myeloid, erythroid, and megakaryocyte progenitor cells but with elevated endogenous levels of erythropoietin, granulocyte colony-stimulating factor, and stem-cell factor. To our knowledge, this is the first report of an aplastic anemia-like syndrome associated with neutralizing antibodies to TPO.
Adenocarcinoma↗
NMR assignment of human ASC2, a self contained protein interaction domain involved in apoptosis and inflammation.
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Apoptosis↗
Pediatric intestinal transplantation: historical notes, principles and controversies.
The development in technique and immunosuppressive management of the last 12 yr have made intestinal transplantation an effective treatment for children with intestinal failure. The information provided in this review support such a conclusion, but was more clearly validated by the March 2001 Medicare Report which provided a national coverage decision of the Social Security Act for intestinal transplantation. As of May 2001, there were 55 centers world-wide which have performed 696 intestinal transplants in 656 patients. (Intestinal Transplant Registry, http://www.lhsc.on.ca/itr) the majority of recipients have been children, and there has been a greater need for liver replacement in conjunction with the allograft intestine because of a higher incidence of TPN-induced cholestatic liver disease in children. Though overall long-term survival is approximately 50%, similar advances in surgical, clinical and immunosuppressive management since 1995 have improved patient survival to more than 70% in most experienced programs. Over 80% of survivors are enjoying nutrition-supporting intestinal function. The major causes of graft loss and patient demise continues to be rejection and infection. Tacrolimus remains the mainstay of immunosuppressive therapy. Further experience other induction protocols utilizing rapamycin and daclizumab, as well graft pretreatment protocols may further enhance results in the future.
Child↗
Viral infections and pediatric liver transplantation.
Viral infections remain an important cause of morbidity and mortality following LTx in children. Increasing experience with both 'donor-associated' and 'community-acquired' viruses is leading to improved outcomes and the development of effective preventive strategies. The potential importance of emerging viral pathogens is an area of active research, which hopefully will also lead to effective treatments and potential preventive strategies for these newly recognized pathogens.
Child↗
EBV viral load monitoring: unanswered questions.
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Epstein-Barr Virus Infections↗
Physician surveys to assess customary care in medical malpractice cases.
OBJECTIVE: Physician experts hired and prepared by the litigants provide most information on standard of care for medical malpractice cases. Since this information may not be objective or accurate, we examined the feasibility and potential value of surveying community physicians to assess standard of care. DESIGN: Seven physician surveys of mutually exclusive groups of randomly selected physicians. SETTING: Iowa. PARTICIPANTS: Community and academic primary care physicians and relevant specialists. INTERVENTIONS: Included in each survey was a case vignette of a primary care malpractice case and key quotes from medical experts on each side of the case. Surveyed physicians were asked whether the patient should have been referred to a specialist for additional evaluation. The 7 case vignettes included 3 closed medical malpractice cases, 3 modifications of these cases, and 1 active case. MEASUREMENTS AND MAIN RESULTS: Sixty-three percent of 350 community primary care physicians and 51% of 216 community specialists completed the questionnaire. For 3 closed cases, 47%, 78%, and 88% of primary care physician respondents reported that they would have made a different referral decision than the defendant. Referral percentages were minimally affected by modifying patient outcome but substantially changed by modifying patient presentation. Most physicians, even those whose referral decisions were unusual, assumed that other physicians would make similar referral decisions. For each case, at least 65% of the primary care physicians disagreed with the testimony of one of the expert witnesses. In the active case, the response rate was high (71%), and the respondents did not withhold criticism of the defendant doctor. CONCLUSIONS: Randomly selected peer physicians are willing to participate in surveys of medical malpractice cases. The surveys can be used to construct the distribution of physician self-reported practice relevant to a particular malpractice case. This distribution may provide more information about customary practice or standard of care than the opinion of a single physician expert.
Expert Testimony↗