Ultrastructural pathology and cytochemical investigations of l-2-chloropropionic acid-induced neurointoxication of the rat cerebellum

The objectives of the studies described were to assess the ultrastructural neuropathology, blood-brain barrier (BBB) integrity and calcium status of the cerebellum of rats following a single dose of 750 mg · kg^–1 l-2-chloropropionic acid (l-2-CPA). The first indications of intoxication appeared at 36 h when condensation of many granule cells associated with Purkinje cell degeneration and marked astroglial swelling were observed. Some electron-lucent granule cells were also noted lying amongst these condensed forms. Condensed granule cells had swollen, electron-lucent mitochondria, dilated Golgi apparatus and nuclear crenation. Occasionally, areas of granule cell necrosis were also present at this time. Granule cell condensation probably represents a preliminary and irreversible stage in an excitotoxic process that leads to necrosis. At 48 and 72 h, most granule cells were necrotic, and occasionally, extravasation of both erythrocytes and leucocytes into the expanded extravascular space was observed. Evaluation of the BBB by ultrastructural cytochemical visualisation of horseradish peroxidase injected i.v. 2 min before killing by perfusion fixation showed substantial leakage. At 36 h post-dose, ultrastructural calcium localisation using oxalate/pyroantimonate precipitation demonstrated a substantial increase in calcium pyroantimonate precipitate in mitochondria and other membranous cytoplasmic organelles (especially the Golgi apparatus) in condensed granule cells, but with little in their nuclei. However, their immediate neighbours (of ostensibly normal ultrastructural appearances) contained greater amounts of intranuclear precipitate. Swollen astroglial cells (especially the Bergmann glia) contained considerable quantities of precipitate. A possible excitotoxic mechanism via l-2-CPA-induced NMDA receptor agonism leading to overwhelming calcium influx and disruption of cellular calcium homeostasis is proposed. Received: 8 May 1996 / Revised: 1 September 1996 / Accepted: 11 September 1996     

PULMONARY RESECTION FOR METASTATIC BREAST CANCER

Background : A patient with a solitary pulmonary metastasis who had breast cancer in the past may benefit from pulmonary resection. Methods : Between 1984 and 1996, 17 patients underwent metastatectomy for metastatic breast cancer. There were 15 females and two males whose average age was 59 (range: 40–74 years). The median tumour-free interval after the primary breast-cancer operation was 5.1 years (range: 8 months-18.2 years). Sixteen patients had complete resections, which included six lobectomies and 10 lesser resections. Results : The postoperative mortality was nil and the morbidity rate was 6%. Follow-up was complete in all patients. Recurrent disease developed in four patients and two patients died of their disease. The 5-year survival was 62%. Conclusion : An aggressive surgical approach is warranted in patients with isolated resectable pulmonary metastases from breast cancer.     

Search for retrovirus in the chronic fatigue syndrome.

AIM: To examine peripheral blood and skeletal muscle from patients with chronic fatigue syndrome for exogenous retrovirus. METHODS: Blood samples from 30 patients and muscle biopsy specimens of 15 patients were examined for retroviral sequences by DNA extraction, polymerase chain reaction (PCR), and Southern blotting hybridisation. Sera were examined for human foamy virus by western immunoblotting and indirect immunofluorescence techniques. RESULTS: No differences between the patient and control populations was found for any of the PCR primer sets used (gag, pol, env, and tax regions of HTLV I/II). An endogenous gag band was observed in both the patient and control groups. All sera were negative for antibody to human foamy virus. CONCLUSION: The results indicate that there is no evidence of retroviral involvement in the chronic fatigue syndrome.     

Adverse outcomes of planned and unplanned pregnancies among users of natural family planning: a prospective study.

OBJECTIVES: The purpose of this study was to determine prospectively whether unplanned pregnancies are associated with adverse pregnancy outcomes among users of natural family planning. METHODS: Women who became pregnant while using natural family planning were identified in five centers worldwide: there were 373 unplanned and 367 planned pregnancies in this cohort. The subjects were followed up at 16 and 32 weeks' gestation and after delivery. The risks of spontaneous abortion, low birth-weight, and preterm birth were estimated after adjustment by logistic regression. RESULTS: The women with unplanned pregnancies were more likely to be at the extremes of age, to report more medical problems before and during the index pregnancy, and to seek antenatal care later in gestation than the women with planned pregnancies. However, women with planned pregnancies reported a higher rate of spontaneous abortion in previous pregnancies (28.8%) than did women with unplanned pregnancies (12.9%). There were no significant differences in the rates of spontaneous abortion, low birthweight, or preterm birth between the two groups. CONCLUSIONS: No increased risk of adverse pregnancy outcomes was observed among women who experienced an unplanned pregnancy while using natural family planning.     

Head injuries in infants and children: Measures to reduce mortality and morbidity in road accidents

In the 6-year period from 1983 to 1988, 12 infants (<24 months of age) and 103 children (2 to 14 years of age) were killed in road crashes in South Australia. This represents an annual incidence of 6.4 deaths per 100,000 children at risk. At least 4 other children were killed in off-road vehicle-related accidents. Of these deaths, approximately half were car passengers, one third pedestrians, and one sixth pedal cyclists. Most of these infants and children died at the accident site or soon after, but 26 of them survived long enough to be admitted to hospitals with neurosurgical units and an audit of these patients suggests that there were at least 3 preventable deaths. However, autopsies of 78 patients show that the great majority of these deaths resulted from devastating brain and/or trunk visceral injuries. Better emergency care and the use of neurosurgical retrieval teams may save some lives. But more lives might be saved by the use of appropriate restraints for infants and children in cars, by reducing the exposure of child pedestrians and cyclists to road traffic, and by mandatory use of helmets by child cyclists. Off-road vehicular accidents are not as a rule included in road crash statistics; the practice of giving small motorcycles to young children has created a new category of vehicular accidents sometimes causing severe head injury.

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Resumen En el período de seis anños 1983–1988, murieron 12 infantes (edades menores de 24 meses) y 103 niños (edades 2–14 años) en accidentes viales en el Sur de Australia, lo cual representa una incidencia anual de 6.4 muertes por 100,000 miños en riesgo. Por lo menos cuatro niños más murieron en accidentes fuera de carreteras pero relacionados con automotores. De tales muertes, approximadamente la mitad correspondió a pasajeros en carros, una tercera parte a peatones y una sexta parte a ciclistas. La mayoría murió en el lugar del accidente o poco tiempo después, pero 26 sobrevivieron un tiempo sufiente para ser hospitalizados en instituciones con unidades neurológicas; una auditoría de tales casos sugiere que por lo menos hubo tres muertes prevenibles. Sin embargo, la autopsia de 78 casos demostró que la mayoría de estas muertes se debió a lesiones devastadores del cerebro y/o las vísceras corporales. Mejores servicios de urgencia y la utilización de equipos de resucitación neuroquirúrgica pueden salvar algunas vidas, pero más vidas pueden ser salvadas mediante el uso de sistemas adecuados de seguridad para infantes y para niños instalados en los carros, reduciendo la exposición de peatones y ciclistas infantiles al tráfico víal y mediante el uso obligatorio de cascos por los ciclistas infantiles. Los accidentes que ocurren por fuera de las carreteras generalmente no son incluídos en las estadísticas de siniestros víales; la costumbre de obsequiar pequeñas motocicletas a niños pequeños ha creado una nueva categoría de accidentes vehículares que en ocasiones causan grave trauma craneano.

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Résumé Pendant la période de six ans allant de 1983 à 1988, 12 enfants âgés de moins de 24 mois et 103 enfants âgés de 2 à 14 ans ont été tués dans un accident de la route en Australie du Sud. Ceci représente une incidence annuelle de 6.4 morts par 100,000 enfants à risque. Au moins quatre autres enfants ont été dans un accident dû à un véhicule motorisé mais hors de la route. Parmi ces morts, la moitié, environ, était des passagers de la voiture, un tiers, des piétons, et un sixième, des cyclistes. La plupart sont morts sur le lieu de l'accident, mais 26 ont survécu suffisamment pour être transportés dans un Hôpital comportant une service de neurochirurgie avant de décéder. Une évaluation de ces accidents mortels a montré qu'au moins trois décès eux étaient évitables. L'autopsie de 78 de ces enfants a démontré que la plupart des décès étaient dus soit à des lésions cérébrales, soit à des lésions viscérales ou du tronc. De meilleurs soins en urgence, et un meilleur déploiment des équipes neurochirurgicales pourraient éviter quelques morts, mais aussi, un certain nombre de morts pourraient être évitées en utilisant correctement less ceintures de sécurité adaptées aux enfants dans les voitures, en réduisant l'exposition aux accidents de ces enfants, ainsi qu'en rendant obligatoire le port de casque pour les enfants se déplacant à vélo. Les accidents qui n'ont pas lieu sur les routes ne sont pas habituelement inclus dans ces statistiques. La croissance de l'utilisation de petits véhicules motorisés par de très jeunes enfants a créé une nouvelle catégorie d'accidents pouvant parfois être responsables de traumatismes crâniens graves.

     

Supply and demand in cerebral energy metabolism: the role of nutrient transporters.

Glucose is the obligate energetic fuel for the mammalian brain, and most studies of cerebral energy metabolism assume that the majority of cerebral glucose utilization fuels neuronal activity via oxidative metabolism, both in the basal and activated state. Glucose transporter (GLUT) proteins deliver glucose from the circulation to the brain: GLUT1 in the microvascular endothelial cells of the blood-brain barrier (BBB) and glia; GLUT3 in neurons. Lactate, the glycolytic product of glucose metabolism, is transported into and out of neural cells by the monocarboxylate transporters (MCT): MCT1 in the BBB and astrocytes and MCT2 in neurons. The proposal of the astrocyte-neuron lactate shuttle hypothesis suggested that astrocytes play the primary role in cerebral glucose utilization and generate lactate for neuronal energetics, especially during activation. Since the identification of the GLUTs and MCTs in brain, much has been learned about their transport properties, that is capacity and affinity for substrate, which must be considered in any model of cerebral glucose uptake and utilization. Using concentrations and kinetic parameters of GLUT1 and -3 in BBB endothelial cells, astrocytes, and neurons, along with the corresponding kinetic properties of the MCTs, we have successfully modeled brain glucose and lactate levels as well as lactate transients in response to neuronal stimulation. Simulations based on these parameters suggest that glucose readily diffuses through the basal lamina and interstitium to neurons, which are primarily responsible for glucose uptake, metabolism, and the generation of the lactate transients observed on neuronal activation.     

Early experience with a novel plaque excision system for the treatment of complex coronary lesions.

The use of directional coronary atherectomy (DCA) in current practice has been limited. The SilverHawk System is a newly developed plaque excision device that aims to overcome the drawbacks of prior DCA platforms. The device was evaluated in a porcine coronary model and in a series of patients. Procedural variables along with outcomes were reviewed. Quantitative angiography (QCA) was performed and excised tissue fragments were weighed and examined histologically. In porcine cases, pretreatment MLD increased from 0.51 +/- 0.26 to 2.36 +/- 0.59 mm postdebulking and 19.9 +/- 7.6 mg of tissue was retrieved. In human cases, pretreatment MLD increased from 0.8 +/- 0.4 to 2.2 +/- 0.5 mm postdebulking and 15.2 +/- 7.8 mg of tissue was retrieved without complications. These data show that the SilverHawk System may offer significant utility in treating a wide variety of complex coronary lesions.     

Tuberculosis risk among migrant farm workers on the Delmarva peninsula.

A survey was conducted to ascertain the risk of tuberculosis (TB) among migrant farm workers on the Delmarva peninsula. Relevant histories were obtained from 842 migrants; a total of 709 skin tests were completed, and 239 sputum specimens were examined for acid-fast bacilli (AFB) and culture. No cases of infectious tuberculosis were ascertained by history or AFB examination. One sputum culture was positive for M. tuberculosis and 13 were positive for various species of nontuberculous mycobacteria. Thirty-seven per cent of migrants tested had significant skin test reactions of 10 mm or more. Reaction rates for men were 41 per cent and for women 25 per cent. Age specific rates ranged from 14 per cent in children aged 5-14 to 54 per cent for ages 45-54. Rates for the principal national/ethnic groups were Haitians 55 per cent, Mexicans 36 per cent, US Blacks 29 per cent and US-born Latinos 20 per cent. Based on these results and other information currently available, it is recommended that current Centers for Disease Control (CDC) recommendations for TB prophylaxis continue to be applied for migrant workers, but that mass screening by skin testing in camp populations not be emphasized. Other recommendations focus on: case finding of active disease, improving continuity and follow-up, increasing coordination among involved agencies, and actively supporting improved economic and living conditions for migrant farm workers.