Case study: worsening Tourette's disorder or withdrawal dystonia?

This case report focuses on withdrawal dystonia, a movement disorder associated with neuroleptics. Its occurrence in a patient with Tourette's disorder complicated the clinical picture. A misinterpretation of the symptoms led to ineffective management of the movement disorder. The presence of increased blinking with facial pain, dystonic movements, and other facial movements at each neuroleptic dose reduction pointed toward withdrawal dystonia rather than toward a worsening of Tourette's disorder. Implications for diagnosis and treatment are discussed.     

Reactivity of small intramyocardial arteries from atherosclerotic and non-atherosclerotic human hearts

Little is known about how the vascular reactivity of the coronary microcirculation is affected by upstream atherosclerotic disease. We have examined, with a wire myograph, the responses of intramyocardial arteries from hearts in which the epicardial vessels were either free of atherosclerotic lesions (non-diseased group) or were affected by atherosclerosis (diseased group). Vasodilator responses of preconstricted vessels to substance P (84.1 +/- 12.6 compared to 42.0 +/- 19.7%) were less in vessels from the diseased group (p < 0.05). In contrast, the relaxation to bradykinin (70.2 +/- 21.2 compared to 100.6 +/- 7.9%) was increased in vessels from the diseased group (p < 0.05). The dilator responses to acetylcholine, adenosine diphosphate, histamine and sodium nitroprusside showed no significant differences between arteries from each group. 5-Hydroxytryptamine was without any significant vasodilator effect in arteries from either group. Assessment of contractile function revealed that the responses to 5-hydroxytryptamine, acetylcholine, U46619, endothelin-1 and L-N(G)-monomethylarginine in each group were not significantly different. Histamine, noradrenaline and dopamine were without any significant contractile response. These results demonstrate that upstream atherosclerosis does not confer any global impairment of endothelium-dependent vasorelaxant responses or smooth muscle hyperreactivity to vasoconstrictors in the arteries that penetrate the myocardium.     

Improved GC/MS analysis of opiates with use of oxime-TMS derivatives

An improved gas chromatographic/mass spectrometric (GC/MS) assay is described for the quantitation of codeine and morphine as trimethylsyl (TMS) derivatives. The TMS derivatization of ketone-containing opiates results in the formation of multiple derivatives. Some of these products have retention times close to those of codeine-TMS and morphine-TMS. When the keto-opiates are present in samples assayed for codeine and morphine in urine, they can interfere with the quantitation of these commonly targeted opiates. The assay was improved with the addition of a pre-BSTFA derivatization step, whereby hydroxylamine was used to convert the keto-opiates into the corresponding oxime derivative. These derivatives were then reacted with BSTFA to form the TMS ethers and TMS oxime derivatives. The oxime step enabled production of single derivatives for hydrocodone and hydromorphone. In addition, the retention times for the oxime-TMS derivatives were increased so that they no longer elute near the targeted drugs of codeine and morphine. The addition of the oxime step does not affect the sylation of codeine and morphine, and the accuracy and precision of this assay were unaffected.     

The MAS proto-oncogene is imprinted in human breast tissue

The human MAS proto-oncogene is situated at 6q25.3-q26, a region that is homologous to mouse chromosome 17 where two parentally imprinted genes (Mas and Igf2r) have previously been identified. We investigated the imprinting status of MAS in adult lesions to establish the imprinting status of this gene in humans, as certain imprinted genes are known to have altered imprinting phenotypes in cancer. Of 14 breast samples demonstrating a MAS RT-PCR product, 4 were informative for a polymorphic marker. In all 4 cases, expression of the MAS gene was found to be mono-allelic, indicating the presence of a functional imprint at this locus in human breast tissue.     

Lung and kidney cancer mortality associated with arsenic in drinking water in Córdoba, Argentina

We have deleted the chromosomal rpsA gene, encoding ribosomal protein S1, from an Escherichia coli strain carrying a plasmid where rpsA was controlled by the lac promoter and operator. This exogenous source of protein S1 was essential for growth. Thus we have verified the absolute requirement for protein S1. To see if translation of individual mRNAs differed in the requirements for protein S1, we removed the inducer and followed the time-course of the synthesis of several individual proteins and of total RNA, DNA and protein. Growth immediately shifted from being exponential to being linear, with a rate of protein synthesis defined by the pre-existing amount of protein S1. The expression pattern of the individual proteins indicated that the translation of all mRNAs was dependent on protein S1. Unexpectedly, we found that depletion for protein S1 for extended periods introduced a starvation for amino acids. Such starvation was indicated by an increased synthesis of ppGpp and could be reversed by addition of a mixture of all 20 amino acids. Measurements of the peptide chain elongation rate in vivo showed that ribosomes without protein S1 were unable to interfere with the peptide chain elongation rate of the active ribosomes and that, therefore, protein S1 was unable to diffuse from one ribosome to another during translation. We conclude that protein S1-deficient ribosomes are totally inactive in peptide chain elongation on most, if not all, naturally occurring E. coli mRNAs.     

Hyperbaric oxygen and thrombolysis in myocardial infarction: the ''HOT MI'' randomized multicenter study

Reactions mediated by the brain are part of the response to intraperitoneal administration of endotoxin, a model of gram-negative bacterial infection. To test the hypothesis that a compromised blood-brain barrier (BBB) may contribute to these reactions, the integrity of the BBB was measured following lipopolysaccharide administration. Rats received intraperitoneal injections of 50 microg/kg or 2 mg/kg of endotoxin. Brain uptake of a macromolecular vascular marker, 3H-labelled rat serum albumin, and of a poorly permeable low molecular weight substance, [14C]sucrose, was then measured with the intravenous bolus injection method. Compared to controls, neither dose of endotoxin affected the BBB permeability for these tracers. This was true when brain uptake was measured 5 min or 2 h after lipopolysaccharide injection. It is concluded that intraperitoneal endotoxin even at a high dose does not acutely disrupt the BBB.