Plasma levels of amino acids correlate with motor fluctuations in parkinsonism

Seven patients with Parkinson's disease who experienced severe motor fluctuations in response to levodopa were studied in detail with relation to the effect of dietary protein on their motor function. The levodopa dose for each patient was not changed during the period of study, and no other antiparkinsonian drugs were used. Regular and high-protein diets resulted in a marked elevation in the plasma concentrations of large neutral amino acids (LNAAs) that are known to compete with levodopa for transport across the blood-brain barrier. Despite elevated plasma levodopa levels, all patients with elevated LNAA levels experienced parkinsonian symptoms. When the amino acid level dropped while plasma levodopa levels were elevated, patients experienced relief of these symptoms. On a low-protein diet, LNAA levels remained low and all patients were consistently dyskinetic throughout the day, even though the mean plasma levodopa levels were somewhat lower than when the patients consumed a high-protein diet. A redistribution diet that is virtually protein free until supper and then unrestricted until bedtime is tolerated by patients because this simple manipulation permits near-normal daytime motor function.     

A primary lung carcinoma producing alpha-fetoprotein, carcinoembryonic antigen, and human chorionic gonadotropin. Immunohistochemical and biochemical studies

This article documents a patient with lung carcinoma that produced three oncofetal antigens including alpha-fetoprotein (AFP), carcinoembryonic antigen (CEA), and human chorionic gonadotropin (hCG). Serum AFP, CEA, and hCG-beta-subunit were extremely high--118,000 ng/ml, 133 ng/ml and 0.9 ng/ml, respectively. Immunohistochemical staining of these tumor markers revealed that these proteins were present in different cells. The pattern of lectin affinity electrophoresis of AFP resembled that of hepatocellular carcinoma. Also investigated was the reactivity of serum CEA to monoclonal antibodies against peptide or sugar moieties. Serum CEA values measured by antipeptide monoclonal antibodies were higher than those measured by antisugar monoclonal antibodies. The demonstration of AFP, CEA, and hCG in different tumor cells suggests that three genomes were not reactivated together in a cell, and the lung carcinoma probably consisted of at least three clones of cancer cells with different phenotypes.     

Effect of repeated exposures to nitrogen dioxide and sulfuric acid mist alone or in combination on mucociliary clearance from the lungs of rabbits

The biological response to ambient air pollution may be a function of specific combinations of pollutants. Groups of rabbits were exposed to NO2 (0.3 ppm or 1 ppm) with and without H2SO4 (0.5 mg/m3) for 2 hr/day for up to 14 days for assessment of effects upon mucociliary clearance of tracer particles from the tracheobronchial tree. Exposure to NO2 did not alter clearance, while exposure to H2SO4 produced a retardation toward the middle of the exposure series. The combination of 0.3 ppm NO2 with H2SO4 resulted in a speeding of clearance, while no change from control was seen with the mixture employing 1 ppm NO2 with acid. These results emphasize the importance of performing studies with pollutant mixtures, since it is not always possible to extrapolate responses from studies examining effects of individual pollutants.     

Inter-study differences: How should they influence the interpretation and analysis of results?

In determining the role inter-study variation should play in an overview analysis, it is important to consider three factors: which question one is trying to answer; the degree of similarity or dissimilarity of design, and the degree to which heterogeneity of outcomes can be explained. Three questions one might be interested in are: whether treatment can be effective in some circumstances; whether treatment is effective on average, and whether treatment was effective on average in the trials at hand. Under the assumption of no qualitative interaction, the answers to these questions coincide. The O-E analysis most directly answers the third question. Other analyses are suggested when the first question is of interest, using the aspirin post-MI studies as an example.     

Renal vascular reactivity in jaundice

Obstructive jaundice is associated with a predisposition to hypotension and acute renal failure that may be related to changes in renovascular responsiveness, particularly to norepinephrine (NE). This study was undertaken to investigate changes in vascular response to NE and to determine how these changes are related to prostaglandins. Kidneys from bile duct-ligated (BDL) rabbits (n = 5) were perfused with Krebs' solution at 7.65 ml/min, and the response to varying boluses of NE (0.78 to 6.24 micrograms) was measured as changes in perfusion pressure. When compared with sham-operated control kidneys (n = 8), a significantly blunted response was seen at all doses tested. The NE response was further assessed by measuring force development in mounted segments of main renal arteries (MRAs) (n = 8) and interlobar arteries (ILAs) (n = 6) from BDL rabbits and sham-operated controls (MRA, n = 8; ILA, n = 6). The dose-response curves were significantly depressed in both MRAs and ILAs from BDL animals. In addition, MRAs from sham-operated control animals exhibited decreased response to NE after incubation for 1 hour in jaundiced serum. This attenuated response of MRAs to NE was prevented when indomethacin (5 mg/kg) was given to BDL rabbits before death (n = 9) or when 10(-6)mol/L of indomethacin was added to jaundiced serum during incubation (n = 6). These results indicate that obstructive jaundice induces a decreased vascular contractile response in rabbits to NE and that this effect is mediated by prostaglandins.