3-Hydroxydicarboxylic aciduria due to long-chain 3-hydroxyacyl-coenzyme A dehydrogenase deficiency associated with sudden neonatal death: protective effect of medium-chain triglyceride treatment

Two siblings were found to be affected by longchain 3-hydroxyacyl-CoA dehydrogenase deficiency, one of which died suddenly and unexpectedly on the 3rd day of life suffering from extreme hypoketotic hypoglycaemia. The younger sibling started to have feeding problems, lowered consciousness, and liver dysfunction at the age of 5 months. Her urine contained large amounts of C₆–C₁₄ 3-hydroxydicarboxylic acids and conjugated 3-hydroxyoctanoic acid, as verified by gas chromatography/mass spectrometry. Plasma long-chain acylcarnitine was increased. A clue to the diagnosis was given by the results of a phenylpropionic acid loading test. This revealed small, but significant amounts of conjugated 3-hydroxyphenylpropionic acid (phenylhydracrylic acid) in the patient's urine. Subsequently, the activity of long-chain 3-hydroxyacyl-CoA dehydrogenase was found to be deficient in cultured skin fibroblasts. Based on the findings obtained by a medium-chain triglyceride load, a diet enriched in this type of fat was prescribed. On this regimen the patient started to thrive, signs of cardiomyopathy disappeared, and her liver function normalized.     

Cell Survival in the Uncrossed Projection of the Mammalian Retina is Independent of Birthdate

Naturally occurring cell loss in the retinal ganglion cell population of one eye can be interrupted by removal of the other eye in newborn rodents. Many of the rescued retinal ganglion cells which project ipsilaterally reside in the nasal retina, that part of the retina normally giving rise to primarily crossed optic axons. Their naturally occurring elimination has been attributed to their hypothesized late neurogenesis and the consequent delayed time of arrival of their axons in the target visual nuclei, thereby placing them at a competitive disadvantage with other, early arriving, optic axons. By combining the technique of tritiated thymidine autoradiography with the retrograde axonal transport of horseradish peroxidase in rats that had been enucleated on the day of birth, we report here that rescued cells in the nasal retina which project ipsilaterally are generated at the same time as their neighbours in the temporal retina. Time of genesis does not distinguish them; consequently, their axons should not differ in their arrival times within the target visual nuclei. Since their only obvious anomaly is one of pathway choice at the optic chiasm, their place of arrival, rather than their time, may ultimately determine their naturally occurring elimination.     

Left Unilateral Inferior Pedunculotomy Prevents Neuronal Death During Postnatal Development of the Remaining Left Inferior Olivary Complex in the Rat

Neuronal death in the inferior olivary complex (IOC) was studied in control and unilaterally pedunculotomized newborn rats, from postnatal day 1 (P1) to P30, in order to test whether the approximately two-fold increase in available specific targets (i.e. Purkinje cells) that is theoretically provided by sectioning one inferior cerebellar peduncle to the developing climbing fibres of the remaining IOC could prevent the loss of inferior olivary neurons taking place during the first 2 weeks of postnatal life in the rat. Numerical estimation of the number of inferior olivary neurons in control and experimental rats showed that (i) in pedunculotomized rats, the number of inferior olivary neurons of the remaining inferior olivary complex was always greater than that encountered in control rats, (ii) the consistent decrease in the number of inferior olivary neurons observed in control animals between P2 and P8 was absent in cell counts of the pedunculotomized rats, and (iii) the increase in olivary cell number following the phase of cell decrease was also absent in pedunculotomized rats. It is concluded that the increase of available Purkinje cells during early postnatal development of the olivocerebellar projection prevents neuronal death in the remaining inferior olivary complex following pedunculotomy.     

Cytotoxic Effect of Brain Macrophages on Developing

Brain macrophages are transiently present in different regions of the central nervous system during development or in the course of tissue remodelling following various types of injuries. To investigate the influence of these phagocytes on neuronal growth and survival, brain macrophages stemming from the cerebral cortex of rat embryos were added to neuronal primary cultures. A neurotoxic effect of brain macrophages was demonstrated by the reduction of the number of neurons bearing neurites within two days of contact between the two cell types. Neuronal death and phagocytosis were also directly observed in video recordings of living cultures. This toxicity involved the production by brain macrophages of reactive oxygen intermediates, as shown by the protective effect of catalase, a scavenger of H2O2. In addition, the respiratory bursts of brain macrophages were stimulated in the presence of neurons. These results suggest that brain macrophages could favour the appearance of neuroregressive events which occur either during neurogenesis or in neurodegenerative diseases, implying intracerebral recruitment of mononuclear phagocytes.     

Blockade of the NMDA receptor increases developmental apoptotic elimination of granule neurons and activates caspases in the rat cerebellum

Elimination of neurons produced in excess naturally occurs during brain development through programmed cell death. Among the many survival factors affecting this process, a role for neurotransmitters acting on specific receptors has been suggested. We have performed an in vivo pharmacological blockade of the N-methyl-D-aspartate (NMDA) subtype of glutamate receptors, using the competitive NMDA receptor antagonist CGP 39551 at developmental stages corresponding to those at which a survival dependence on the stimulation of this receptor has been demonstrated for cerebellar granule neurons explanted in culture (typically from postnatal day 7 to postnatal day 11 or 13). We were able to demonstrate an increased level of DNA fragmentation in the cerebellum of the treated rats. At the P11 stage, in particular, the fragmented DNA extracted from the cerebellum of CGP 39551-treated pups showed a clear laddering of nucleosomal fragments after agarose-gel electrophoresis. Accordingly, in situ TUNEL technique showed a remarkable increase of cells positive for nucleosomal DNA fragmentation, particularly in the inner granular layer of the cerebellum of treated rats at P11 stage. Therefore, the natural rate of apoptotic elimination of cerebellar granule neurons is considerably enhanced under conditions of pharmacological blockade of the NMDA receptor, thus demonstrating, for the first time in vivo, a clear survival dependence of these neurons upon the stimulation of the NMDA receptor. Concomitantly with the increased rate of apoptotic elimination of granule neurons, the activity of two death proteases of the caspase family, in particular of caspase 3 and caspase 1 at a lower extent, was remarkably increased in the cerebellum of the treated rats. On the contrary, a marker related to the normal differentiation process of granule neurons, the enzyme ornithine decarboxylase, was strongly decreased in its activity in the cerebellum of treated rat pups.     

突发性聋患者血浆一氧化氮和内皮素含量的测定

目的 :探讨血浆一氧化氮 (NO)和内皮素 (ET)水平在突发性聋 (突聋 )发病过程中的作用。方法 :对32例突聋患者用硝酸还原酶法测定血浆NO ,用放射免疫法测定血浆ET。结果 :突聋组血浆NO显著降低 ,ET显著升高 ,与正常对照组相比较 ,突聋组血浆NO显著降低 (P <0 .0 1) ,ET显著升高 (P <0 .0 1) ;突聋治疗前与治疗后血浆NO、ET之间差异有显著性意义 (P <0 .0 1) ;治疗有效者与无效者血清NO、ET水平的差异也有显著性意义 (P <0 .0 1)。结论 :在突聋发作过程中 ,血浆NO和ET的含量显著变化 ,可能促进了疾病的发生和发展     

Autopsy study of maternal deaths.

OBJECTIVES: To obtain an insight into the underlying disorder or pathologies in different organs or systems, and to attempt clinicopathologic correlation in maternal deaths. METHODS: This is a retrospective study of 95 maternal autopsies done from 1993 to 2000 in Sassoon General Hospital, Pune, India. External examination, in situ examination, gross and microscopic examination was done in each case. The cause of death was arrived at after reviewing clinical details, available investigations, morphological findings, and clinicopathologic correlation. RESULTS: Ninety-five (45.02%) out of 211 maternal deaths were autopsied. Out of 95, there were 47 (49.5%) direct obstetric deaths, and 33 (34.7%) indirect obstetric deaths. Fifteen (15.8%) deaths were unrelated to pregnancy, 14 of which were due to infections. CONCLUSIONS: Hypertensive disorders associated with pregnancy (24.2%) and anemia (14.7%) were most common. In the hypertensive group, important findings were disseminated intravascular coagulation, hemorrhages in different organs and thromboemboli. Two cases were HIV seropositive. The autopsy helped to elucidate factors contributing to death and pathology in different organ systems.     

肿瘤坏死因子-β抗肿瘤及作用机制的研究

目的 :探讨肿瘤坏死因子 -β(tu mornecrosisfactor β ,TNF β)对 3种人癌细胞的增殖抑制作用及其细胞分子机制。方法 :采用多种体外及体内实验方法 ,从多侧面证实TNF β的抗肿瘤作用。并采用细胞内游离钙浓度测定、12 5I cAMP放免检测法检测cAMP含量。结果 :不同浓度TNF β对肿瘤细胞系均有增殖抑制作用 ,且呈剂量依赖性。当TNF β与顺铂和多柔比星合用 ,JF3 0 5细胞死亡百分比分别达到 ( 68 6±9 0 ) %和 ( 76 5± 7 9) %。TNF β实验组细胞内cAMP浓度明显增加 ,JF3 0 5细胞由( 0 0 5 72± 0 0 176)上升到 ( 0 2 896±0 0 784) pmol/10 6个细胞。此外细胞内钙浓度上升并且凋亡。结论 :TNF β具有体内、外抗肿瘤作用 ,其部分机制是通过增加cAMP含量及诱导细胞凋亡     

Interactions between maternal smoking and other prenatal risk factors for sudden infant death syndrome (SIDS)

Abstract In numerous investigations, maternal smoking increases the risk of sudden infant death syndrome (SIDS). In the present study we investigated whether prenatal risk factors for SIDS modify the effect of maternal smoking on SIDS mortality. We analysed data from a population-based cohort study (222 cases, 260,604 infants at risk) within the Westphalian Perinatal Inquiry in Germany between 1990 and 1994. In the stratified analysis, smoking was classified into non-smoking, moderate (1–10 cigarettes/d) and heavy smoking (> 10 cigarettes/d). Multiplicative interactions between smoking and other prenatal risk factors were assessed in a logistic regression model. The relative risk (RR) for maternal smoking was 2.4 (95% confidence interval 1.7-5.4) for moderate and 7.2 (5.3, 9.7) for heavy smokers. Previous established risk factors for SIDS, such as preterm birth, low birthweight, and number of prenatal visits did not increase the risk of SIDS among non-smokers, but became important risk factors among smokers. In preterm infants (< 37 weeks) of heavy smokers, the RR was 19.6 (10.4, 36.8) compared to term infants of non-smokers. Low birthweight infants (< 2500 g) of heavy smokers had a RR of 16.3 (8.4, 31.2) compared to normal weighted infants of non-smokers. Adjustment for occupational status did not change the crude estimates. The RR of < 6 prenatal visits in the heavy smoking subgroup was 14.8 (7.2, 29.6) compared to > 9 prenatal visits in the nonsmoking strata. Heavy smoking potentiates other prenatal risk factors for SIDS suggesting an increased susceptibility towards the adverse effects of tobacco smoke in utero. In infants born to non-smoking mothers, prenatal risk factors are absent and postnatal factors may be of major importance.     

Registration of cancer mortality data in a developing area: Chennai (Madras, India) experience

Objectives: This study was carried out to evolve a method to improve the registration of cancer mortality data in Chennai (Madras, India). Methods: Data on cancer deaths have been collected from the Vital Statistics Department (VSD) by a population-based cancer registry (PBCR) in Chennai only since 1982. The low mortality-to-incidence ratio during 1982-84 suggested under-registration of mortality data. Since 1985, the PBCR has taken special effort to ascertain the vital status of cancer cases by sending reply-paid postcards and/or making house visits. The data on all deaths occurring in Chennai, irrespective of stated cause of death in the death certificate, have been collected from the VSD since 1992. Results: Deaths that occurred in Chennai and obtained by sending reply-paid postcards and/or making house visits were registered in VSD as non-cancer causes of death; hence, these data were not collected from VSD. The sensitivity and positive predictive values of death certificates on cancer diagnosis based on 1992 and 1993 mortality data were 57 percent and 99.5 percent, respectively. Conclusion: Since the accuracy of death certificate information on cancer diagnosis is relatively low in a developing country such as in India, collecting data on all deaths will improve the mortality data registration in PBCRs.