Idiopathic cardiomyopathy in infants

Nine cases of cardiomyopathy in infants are described. The early age of occurrence suggests the possibility of an intrauterine onset, and the finding of virus antibodies to a significant titre in 3 of the 4 mothers examined suggests intrauterine viral infection as a possible cause.The degenerative changes which have previously been described in cardiac ganglia are confirmed, but they are also found in control material, and are believed to be associated with cardiac failure rather than be features attributable to virus infection.     

Determinants of prescribing meperidine compared to morphine in hospitalized patients

Morphine is a preferred narcotic since meperidine forms toxic metabolites. Determinants of meperidine use have been poorly described. The objective of this study is to explore factors associated with the ordering of meperidine versus morphine. Retrospective chart review of adult patients, randomly selected based on orders for morphine or meperidine. 1552 orders were written for 670 patients. Of these, 36% were for meperidine. In multivariable analysis, the ordering of meperidine was associated with the following variables in decreasing order of importance: physician specialty, total doses received, hospital location, patient race, age and insurance, and physician gender. More orders for meperidine were written for those receiving fewer doses. Though meperidine has little role in the routine management of hospital pain, we found it continues to be used frequently. Importantly, meperidine is ordered more frequently for patients who receive shorter courses of narcotics. Our study suggests that interventions targeted at more appropriate use of meperidine rather than complete elimination might be more acceptable to physicians while minimizing the risk of toxicity.     

Lipopolysaccharide fever is initiated via a capsaicin-sensitive mechanism independent of the subtype-1 vanilloid receptor

As pretreatment with intraperitoneal capsaicin (8-methyl-N-vanillyl-6-nonenamide, CAP), an agonist of the vanilloid receptor known as VR1 or transient receptor potential channel-vanilloid receptor subtype 1 (TRPV-1), has been shown to block the first phase of lipopolysaccharide (LPS) fever in rats, this phase is thought to depend on the TRPV-1-bearing sensory nerve fibers originating in the abdominal cavity. However, our recent studies suggest that CAP blocks the first phase via a non-neural mechanism. In the present work, we studied whether this mechanism involves the TRPV-1. Adult Long-Evans rats implanted with chronic jugular catheters were used. Pretreatment with CAP (5 mg kg(-1), i.p.) 10 days before administration of LPS (10 microg kg(-1), i.v.) resulted in the loss of the entire first phase and a part of the second phase of LPS fever. Pretreatment with the ultrapotent TRPV-1 agonist resiniferatoxin (RTX; 2, 20, or 200 microg kg(-1), i.p.) 10 days before administration of LPS had no effect on the first and second phases of LPS fever, but it exaggerated the third phase at the highest dose. The latter effect was presumably due to the known ability of high doses of TRPV-1 agonists to cause a loss of warm sensitivity, thus leading to uncontrolled, hyperpyretic responses. Pretreatment with the selective competitive TRPV-1 antagonist capsazepine (N-[2-(4-chlorophenyl)ethyl]-1,3,4,5-tetrahydro-7,8-dihydroxy-2H-2-benzazepine-2-carbothioamidem, CPZ; 40 mg kg(-1), i.p.) 90 min before administration of LPS (10 microg kg(-1), i.v.) or CAP (1 mg kg(-1), i.p.) did not affect LPS fever, but blocked the immediate hypothermic response to acute administration of CAP. It is concluded that LPS fever is initiated via a non-neural mechanism, which is CAP-sensitive but RTX- and CPZ-insensitive. The action of CAP on this mechanism is likely TRPV-1-independent. It is speculated that this mechanism may be the production of prostaglandin E(2) by macrophages in LPS-processing organs.     

Preimplantation genetic diagnosis of chromosome abnormalities: implications from the outcome for couples with chromosomal rearrangements

OBJECTIVES: Chromosomal rearrangements can lead to infertility or repeated spontaneous or induced abortions. The use of preimplantation genetic diagnosis (PGD) allows the selected transfer of chromosomally balanced embryos. The aim of this study was to carry out detailed analysis of the outcome of 11 PGD cycles for 8 patients carrying various chromosomal rearrangements. METHODS: Patients underwent routine in vitro fertilisation with biopsy of embryos on day 3. Specific fluorescent in situ hybridisation protocols were developed for each couple. Embryo transfer was possible in all 11 cycles. RESULTS: The outcome was four pregnancies, leading to three live births and one biochemical pregnancy. Post-zygotic mosaicism was detected in 75% of untransferred embryos, the majority of which were chaotic. Detailed follow-up and analysis provided evidence for the co-existence of chromosomally balanced and abnormal cells in six embryos. The mechanisms involved included chromosome breakage and loss of material. CONCLUSIONS: Biopsy and analysis of two blastomeres, where possible, reduced the risk of misdiagnosis in cases of balanced/aneuploid mosaics. The three live births achieved for the eight couples treated in this series, despite the poor history in almost all cases, is further proof that a policy of biopsying two cells from embryos consisting of six or more cells and a single cell from four- or five-cell embryos is compatible with a positive outcome.     

A national survey in England of the routine examination of the newborn baby

OBJECTIVE: To identify current practices for the initial routine examination of healthy newborn babies, and determine the extent to which midwives are carrying out this examination. DESIGN AND PARTICIPANTS: Postal questionnaires were sent to consultant paediatricians and midwifery managers in all maternity units in England. Questionnaires were also sent to the 12 universities in England which run the N96 post-registration course in the examination of the newborn baby. FINDINGS: Questionnaires were returned from 197 (86%) maternity units. Senior house officers examined in 83% (160/193) a median of 92% of babies; 44% (74/167) had at least one midwife (median of two) with qualifications to carry out the examination and in 31% (51/167) some examinations were conducted by a midwife. However, a third of midwives with this qualification carried out no examinations, and nationally only about 2% of babies were examined by a midwife. Rates of referral by midwives and senior house officers were similar. Examinations were carried out between four and 48 hours from birth; most units considered six hours an acceptable minimum. An estimated 1% of babies were transferred home without routine examination; the GP was responsible for most (83-93%) of these babies' examinations; midwives for 10-23%; and senior house officers in hospital for 4-7%. Twelve per cent (23/194) of units carried out a second examination prior to discharge. Most respondents were in favour of midwives carrying out the examinations provided they were adequately trained. CONCLUSIONS: Many of the consultant paediatricians and midwifery managers stated that suitably trained midwives could routinely examine the healthy newborn baby; however, many currently N96 trained midwives were examining few or no babies. An extension of training would be needed were midwife examination to become general policy.     

Economic analyses of respiratory syncytial virus immunoprophylaxis in high-risk infants: a systematic review

OBJECTIVE: To systematically review all published economic analyses of the only 2 available agents for respiratory syncytial virus immunoprophylaxis in high-risk infants: respiratory syncytial virus immunoglobulin intravenous and palivizumab. DATA SOURCES: Economic evaluations of respiratory syncytial virus immunoprophylactic agents were identified from the MEDLINE and HealthSTAR databases using various combinations of the following search terms: respiratory syncytial virus immunoglobulin intravenous, palivizumab, cost, and cost-effectiveness. The search was limited to articles published in English between January 1, 1990, and August 31, 2001. Additional studies were obtained by searching bibliographies of all relevant identified articles. STUDY SELECTION: Only studies that performed an economic analysis of either or both of these agents in an infant population were included. Letters to the editor and commentaries that included informal economic analyses were excluded. Twelve of the 21 identified studies met the selection criteria. DATA EXTRACTION: Two of us (S.K.-B. and J.D.) independently reviewed the articles and extracted summary information using a standardized abstraction form, with differences resolved by consensus. DATA SYNTHESIS: Estimates ranging from cost savings to considerable incremental costs per hospitalization avoided with use of either agent were observed across studies. Studies comparing the 2 agents reported mixed results about their relative cost-effectiveness in different infant subgroups. The divergent results may be explained by differences in the study methods and assumptions, but they also reflect the poor quality of some of the economic analyses. CONCLUSION: In light of the issues identified in this review, providers, payers, and health policymakers need to critically appraise and judiciously interpret cost-effectiveness research on these agents.     

Enhanced ability of the progenipoietin-1 to suppress apoptosis in human hematopoietic cells

Repopulating hematopoietic cell compartments after myeloablative chemotherapy remains a key factor in a successful chemotherapy program. Modified and chimeric cytokines have been developed to help reduce inflammation, fever and hospitalization time for patients. A chimeric cytokine, progenipoietin-1 (ProGP-1), containing the G-CSF and FL receptor agonists binds both the G-CSF receptor and FLT-3. It also stimulates the growth of dendritic cells, which play an important role in immunotherapy. While in vivo effects of ProGP-1 are well described, the mechanisms by which it stimulates growth are not well understood. We have investigated the effects of ProGP-1 on prevention of apoptosis in the human hematopoietic cell line OCI-AML.5. ProGP-1 promoted cellular proliferation better than G-CSF or FL separately but stimulated proliferation similar to their co-addition as demonstrated by growth curves and [3H]-thymidine incorporation. ProGP-1 prevented apoptosis to a greater degree than G-CSF or FL alone as determined by annexin V/propidium iodide binding and TUNEL assays. ProGP-1 promoted maintenance of the mitochondrial membrane potential better than G-CSF or FL alone. In addition, Pro-GP promoted a lower redox potential as higher levels of free radicals were detected after cytokine treatment than in cytokine-deprived cells implying increased respiration. These data indicate that ProGP-1 promotes the proliferation and prevents the apoptosis of human hematopoietic cells better than FL or G-CSF alone, and to a similar extent as their co-addition. Thus, ProGP-1 can be used to repopulate certain hematopoietic cells as a single entity rather than the introduction of two different cytokines.