Mitochondrial enzyme expression in the hippocampus in relation to Alzheimer-type pathology.

Recent reports have suggested that mitochondrial dysfunction may contribute to the progression of the pathology of Alzheimer's disease (AD). However, both increases and decreases in the activity of cytochrome oxidase have been described in the hippocampi of AD patients. In this study we used immunohistochemistry and quantitative autoradiographic methods to study the expression pattern of two cytochrome oxidase subunit proteins (nuclear-encoded COX IV and mitochondrial-encoded COX I) in the hippocampus in relation to the development of AD-type pathology. We found heterogeneous expression of both COX subunits in AD with an increased expression of both subunit proteins in healthy, non-tangle-bearing, neurones but absence of both subunit proteins in tangle-bearing neurones. Levels of COX IV but not of COX I were related to the amount of hyperphosphorylated tau accumulated in the same hippocampal region but not to the amount of amyloid deposited in sporadic AD. In Down's syndrome COX I and COX IV were similarly increased in the presence of AD pathology in non-tangle-bearing neurones. However, in these cases levels of enzyme expression were correlated to the amount of amyloid accumulation but not the amount of hyperphosphorylated tau in the hippocampus. We believe that heterogeneity of expression of mitochondrial enzyme proteins between neurones may contribute to the conflicting conclusions in previous reports regarding relative levels of cytochrome oxidase activity in the hippocampus in AD. We hypothesise that the increased mitochondrial enzyme expression in healthy-appearing neurones of AD brains may represent a physiological response to increased functional demand on surviving neurones as a consequence of AD-related neuronal pathology.

Noise exposure profile among heavy equipment operators, associated laborers, and crane operators.

This study, conducted in 1987 and 1988, has made it possible to quantify exposure to noise among heavy equipment operators, associated laborers, and crane operators. The average daily noise exposure was 84 to 99 dBA for heavy equipment, 90 dBA for the laborer, and 74 to 97 dBA for the crane operator. The main sources of noise to which heavy equipment operators are exposed are vehicle engines and the muffler exhaust system, usually located near the operator. The presence of insulated cabs such as those found on power shovels, backhoes, wheel loaders, and graders help reduce noise exposure. The type of tasks carried out by the laborers, the sources of noise from heavy equipment around which they work, and the manual equipment they use determine the noise levels to which such workers are exposed. In the case of crane operators, an insulated cab significantly reduces the operator's exposure to engine noise.

Cerebral dysgenesis and lactic acidemia: an MRI/MRS phenotype associated with pyruvate dehydrogenase deficiency.

Pyruvate dehydrogenase complex (PDHC) is an intramitochondrial multienzyme complex essential for the aerobic oxidation of glucose. The majority of patients with PDHC deficiency have abnormalities in the major catalytic and regulatory subunit, E1 alpha, which is encoded on the X chromosome. The clinical spectrum of PDHC deficiency is heterogeneous, particularly in heterozygous females, and diagnosis may be difficult. Three affected infant girls with PDHC deficiency were investigated. All had dysmorphic features, microcephaly with profound global developmental delay, and hypotonia. Systemic acidosis was absent, although serum lactate and pyruvate were abnormally elevated. Magnetic resonance imaging revealed hypoplasia of the corpus callosum in all patients. Proton magnetic resonance spectroscopy of brain revealed large increases in relative signal intensities for lactic acid and decreases in the relative signal intensities of N-acetylaspartate, a marker of neuronal damage or less. Phosphorus MRS of muscle revealed abnormally low phosphorylation potentials for all these patients, although the degree of abnormality was variable and not directly correlated with the amount of brain lactate. It is proposed that cerebral dysgenesis and cerebral lactic acidemia as shown by magnetic resonance imaging and proton magnetic resonance spectroscopy are useful diagnostic clues to PDHC deficiency, particularly in females in whom variable patterns of X-inactivation reduce sensitivity of laboratory diagnosis based on the biochemical studies of peripheral tissues. In addition, muscle bioenergetic abnormalities in conjunction with CNS dysfunction may contribute to profound hypotonia in this disorder.

Pyruvate dehydrogenase deficiency. Clinical presentation and molecular genetic characterization of five new patients.

Fibroblast cultures from five patients with early onset severe encephalopathy and lactic acidosis were studied for evidence of pyruvate dehydrogenase (PDH) deficiency. Three males had significantly reduced activity (0.29-0.45 nmol/mg protein/min versus normal controls 0.7-1.1 nmol/mg protein/min); two females had PDH activity within the normal range. However, as the majority of cases of PDH deficiency result from defects in the X-linked E1 alpha subunit and both females had biased patterns of X-inactivation (making it impossible to rule out the possibility that they were heterozygous for an E1 alpha gene defect) molecular genetic studies were performed. cDNA from the male patients was sequenced and mis-sense mutations found: Y243N (T-->A) in exon 7, D315A (G-->A) in exon 10 and R378H (G-->A) in exon 11. Single-strand conformation polymorphism analysis of amplified genomic DNA fragments and sequencing revealed a mis-sense mutation M282L (A-->C) in one female and a frameshift mutation caused by insertion of T (R288ins) in the other. Adding to recent descriptions of new mutations, this report emphasizes the allelic heterogeneity of the condition. The identification of mutations in females with a suggestive clinical phenotype, even when peripheral fibroblasts do not show deficient PDH activity, illustrates the importance of molecular analysis of this disease.

Hypodermoclysis for the administration of fluids and narcotic analgesics in patients with advanced cancer.

Fifty-eight consecutive patients with advanced cancer who required parenteral hydration were treated with hypodermoclysis. A solution of two-thirds 5% dextrose and one-third saline was used in all cases at a rate of 20-100 cc/hr, with 750 units of hyaluronidase per liter, and 20-40 mEq KCl/L were administered in all patients. In 38 patients, morphine (21 cases) or hydromorphone (17 cases) were added. The mean duration of infusion and volume were 14 +/- 9 days and 1.3 +/- 0.8 L/day, respectively (range, 0.5-3 L/day). Mean dose of KCl was 25 +/- 8 mEq/L. The reason for discontinuation was death in 43 cases, oral hydration in 12 cases, and need for fluid restriction in 3 cases. Toxicity consisted in local infection in two cases and bruising in two cases. We conclude that hypodermoclysis is a safe and effective method of hydration in patients with advanced cancer.

[Results of detection and early treatment of Chlamydia trachomatis infections in pregnancy]. / Résultats du dépistage et traitement précoce des infections à Chlamydia trachomatis au cours de la grossesse.

The authors report and comment on the results of a prospective study of the usefulness of early treatment of Chlamydia trachomatis infections in pregnant women. The diagnosis is based on a serological examination carried out in the first trimester of pregnancy. 60 women were treated by antibiotics and they were compared with 51 women who were not treated. The two groups were statistically comparable. There was a significant drop in perinatal complications due to Chlamydia trachomatis. The difference was particularly significant as far as low birth weight and the incidence of conjunctivitis in the newborn was concerned. These results show how useful it is to carry out serological screening and early treatment of Chlamydia trachomatis infections in pregnancy.

[Pharyngeal epignathus teratoma. Echographic and prognostic study]. / Tératome pharyngé épignathe. Etude échographique et pronostic.

Pharyngeal epignathus teratoma is an isolated benign tumour, but the prognosis is very indeed because it can so easily obstruct the respiratory or the digestive pathways. Only rarely has this teratoma been diagnosed by ultrasound in the literature. The authors, having had a personal case, decided to discuss the problems in making the diagnosis by ultrasound and in deciding what treatment to carry out.

[Uterine retroversion. A simple surgical cure]. / Rétroversion utérine. Cure chirurgicale simple.

In 20% of the cases, painful symptoms which cannot be dismissed in general practice are experienced by women with uterine retrodeviation. The technique described here is based on anatomical reduction of Douglas' pouch with restoration of tension in the uterosacral ligaments. It is simple and rapid as expected for a minor anatomical defect. The creation of two perpendicular peritoneo-ligamentous planes ensures its solidity. The effectiveness and safety of this technique has been confirmed by a series of more than 70 patients 50% of whom were examined at regular intervals for more than 5 years after surgery.