In vivo electrochemical studies of dopamine overflow and clearance in the striatum of normal and MPTP-treated rhesus monkeys

Translational recruitment of maternal mRNAs is an essential process in early metazoan development. To identify genes required for this regulatory pathway, we have examined a collection of Drosophila female-sterile mutants for defects in translation of maternal mRNAs. This strategy has revealed that maternal-effect mutations in the cortex and grauzone genes impair translational activation and cytoplasmic polyadenylation of bicoid and Toll mRNAs. Cortex embryos contain a bicoid mRNA indistinguishable in amount, localization, and structure from that in wild-type embryos. However, the bicoid mRNA in cortex embryos contains a shorter than normal polyadenosine (poly(A)) tail. Injection of polyadenylated bicoid mRNA into cortex embryos allows translation demonstrating that insufficient polyadenylation prevents endogenous bicoid mRNA translation. In contrast nanos mRNA, which is activated by a poly(A)-independent mechanism, is translated in cortex embryos, indicating that the block in maternal mRNA activation is specific to a class of mRNAs. Cortex embryos are fertilized, but arrest at the onset of embryogenesis. Characterization of grauzone mutations indicates that the phenotype of these embryos is similar to cortex. These results identify a fundamental pathway that serves a vital role in the initiation of development.     

Epidemiology of work-related aviation fatalities in Alaska, 1990-94

Alaska, with less than one-half of 1% of the United States workforce, accounts for 9% of all occupational aviation fatalities nationally; 30% of all occupational fatalities in Alaska are related to aviation. To understand this high mortality, we investigated occupational aviation crashes to identify risk factors. Occupational aviation fatalities in Alaska during 1990-94 were examined using National Transportation Safety Board reports and merged with records from the Alaska Occupational Injury Surveillance System. There were 876 aircraft crashes; 407 (46%) were work-related. Occupational crashes were 2.2 times (CI: 1.5, 3.2) more likely to result in fatalities than non-occupational crashes. Risk factors identified included poor weather conditions defined as Instrument Meteorological Conditions (IMC). A crash during IMC was 5.3 times (CI: 3.5, 7.9) more likely to result in fatalities than crashes in other conditions. Of aircraft involved in fatal occupational incidents, 33% were not completely destroyed, allowing the potential for survivors. An estimated 30% reduction in fatalities could have occurred if current technology in occupant protection had been used.     

Medical management of benign prostatic hyperplasia: a review

Benign prostatic hyperplasia (BPH) is a common disease affecting elderly men with 70% of men over 70 years showing microscopic evidence of hyperplasia. Transurethral resection of the prostate is the gold standard treatment. Medical management of BPH has involved the use of plant extracts, amino acids, kampo and animal organ preparations in various countries with unsatisfactory results. The use of alpha adrenergic antagonists dates back twenty years representing a major breakthrough in the treatment by relaxation of the dynamic contraction of smooth muscle component of prostatic obstruction. The evolution of alpha antagonist therapy resulted in clinical trials with selective antagonists such as prazosin, alfuzosin, indoramin, terazosin and doxazosin all of which achieve similar effective relief of obstructive symptoms as phenoxybenzamine, but with fewer side effects related to postural hypotension. 5-alpha reductase inhibitors, finasteride and episteride, recently synthesised act on the static component of obstruction caused by the enlarging prostate. They inhibit conversion of testosterone to the potent intracellular androgen dihydrotestosterone (DHT) resulting in the reduction of prostate volume and improvement of obstructive symptoms. Clinical trials with finasteride for three years indicate that 63% of patients had a reduction of greater than 20% in prostatic volume and 42% had a decrease of greater than 30% with a mean increase peak flow rate of 2.4 mls/s equivalent, to 20 years reversal of disease progression.     

Chronic d-fenfluramine treatment reduces fat intake independent of macronutrient preference

The origin of hematopoietic stem cells (HSCs) and their growth factor requirement are poorly understood. Here we describe a new in vitro culture system of the aorta-gonad-mesonephros (AGM) region, where long-term repopulating HSCs first arise. We demonstrate that oncostatin M (OSM) is expressed in the AGM and is absolutely required for the expansion of multipotential hematopoietic progenitors in vitro. In addition, OSM enhances the formation of endothelial cell clusters. Thus, OSM appears to be a key cytokine for the development of multipotential hematopoietic progenitors in the AGM, possibly acting on common precursor cells between HSCs and endothelial cells. By using the AGM culture derived from macrophage colony-stimulating factor (M-CSF)-deficient op/op mutant embryos, we also show a pivotal role for M-CSF in fetal myelopoiesis.     

Fate of wheat bound malathion residues in rats during gestation

Malathion [S-1,2-di(ethoxycarbonyl) ethyl 0,0-dimethyl phosphorodithioate], treated wheat when stored for 28 months at 20 degrees C with or without food grade white mineral oil on grains contained about 62 and 79% of the applied insecticide as bound residues, respectively. These bound residues were present mainly in the form of the parent compound. The stored wheat containing bound malathion residues, as well as wheat material freshly spiked with malathion were fed to rats during gestation. No residues of malathion and/or metabolites were detected in urine, feces and body tissues. Further no significant effect on body weight, serum chemistry and cytochrome P450 levels were observed in the mothers. There was no evidence for the histopathological alteration or teratogenic anomalies in the fetuses. However, placental transfer of malathion was indicated by the presence of the insecticide residues in fetuses from rats fed wheat material containing bound residues.     

Adrenal cortex response to adrenocorticotropic hormone in dairy cattle

Adult dairy cows were treated with a range of doses (0.0125mg to 0.4mg) of synthetic ACTH1-24 and the plasma cortisol response was measured. Peak response was independent of dose. Higher doses of ACTH had a more prolonged effect such that the integrated response was dose dependent. Dose response curves were examined by regression analyses. Individual cows had a significant effect on y-axis intercept but not on the slope of the regression lines examined. A dose rate of 0.05mg ACTH iv was identified as a suitable dose rate for use in clinical assessment of adrenal cortex function, with 0, 50 and 120 min following ACTH being critical sampling times to identify the response.     

Acute knee injuries: Part I. History and physical examination

A thorough history and physical examination are helpful in the diagnosis of meniscal damage, cruciate and collateral ligament sprains and patellar instability, the four major acute knee injuries. When performing a physical examination in a patient with a knee injury, the uninjured knee should always be assessed first and used for comparison. Examination includes passive and active range-of-motion testing, palpation of the joint line spaces, and a variety of maneuvers to evaluate knee stability. Valgus and varus testing provides assessment of the collateral ligaments. The Lachman and pivot shift tests are useful in the evaluation of the anterior cruciate ligament. The posterior drawer and tibial sag tests are used to evaluate the posterior cruciate ligament. The bounce test, McMurray's test and Apley's grind test can aid in the diagnosis of meniscal injury.     

Degradation kinetics of DMP 777, an elastase inhibitor

PURPOSE: The objective was to evaluate the degradation profile of the elastase inhibitor DMP 777 and lay the foundation for formulation development. METHODS: The pKa was determined by potentiometric titration in mixed-aqueous solvents. The degradation kinetics were studied as a function of pH, buffer concentration, ionic strength, methanol concentration and temperature using a stability-indicating HPLC assay. The degradation products were identified by LC-MS, NMR, and by comparison with authentic samples. RESULTS: The pKa for the protonated piperazine nitrogen was estimated to be 7.04. The pH-rate profile is described by specific acid-, water-, and specific base-catalyzed pathways. The pH of maximum stability is in the range of 4 to 4.5 where water is the principal catalyst in the reaction. Buffer catalysis, primary salt effects and medium effects were observed. The proposed mechanism for acid catalyzed degradation is the rarely observed AAL1 which involves alkyl-nitrogen heterolysis. The driving force for the reaction appears to lie in the stability of the benzylic carbocation. The proposed mechanism for base catalyzed degradation is BAC2 which involves beta-lactam ring opening. The beta-lactam ring of DMP 777, a monolactam, appears to be as reactive as that in benzylpenicillin in the KOH controlled region where a similar mechanism of hydrolysis should be operative. A contributing factor to this increased reactivity may lie in the reduced basicity of the beta-lactam nitrogen making it a good leaving group. CONCLUSIONS: The degradation profile indicates that development of a solution dosage form of DMP 777 with adequate shelf-life stability at room temperature is feasible.     

Surgical treatment of mesotympanitis

A chronic sluggish suppuration in the middle ear, mesotympanitis, leads to impairment of sound conduction and onset of hypoacusis. Otogenic labyrinthopathy is also possible. As to complications, present-day course of mesotympanitis is close to epitympanitis. Intensive conservative therapy should be followed by revision of the middle ear system earlier than 4-6 months of remission. In minor lesions tympanoplasty with retroauricular drainage of the antrum is indicated, in serious affection surgical intervention is needed.