Unilateral versus bilateral tasks in early asymmetric Parkinson's disease: differential effects on bradykinesia.

Patients with Parkinson's disease (PD) have an impaired ability to perform two different simultaneous bimanual tasks. The differential effects of unilateral versus bilateral identical tasks on the bradykinesia scores of the more and less affected limbs in PD have not been examined. Twenty-seven patients with early and asymmetric PD underwent blinded, videotaped assessment, independently for each limb, using the bradykinesia items of the Unified Parkinson's Disease Rating Part III, Motor subscale (mUPDRS) and a Modified Bradykinesia Rating Scale (MBRS), which assessed amplitude, speed, and rhythm of movements. We found that the score for finger tapping in mUPDRS and MBRS, the score of amplitude of finger tapping in MBRS, and the lateralized scores of mUPDRS (sum of Items 23 to 25) of the most affected side significantly improved during the bimanual task. The improvement was associated with longer duration of illness, higher total scores in mUPDRS, and higher lateralized bradykinesia scores of the most affected side. There was a simultaneous deterioration of the lateralized bradykinesia scores in MBRS (sum of Items 23 to 25) and Item 25 of mUPDRS (rapid alternating movements) of the least affected side in bimanual tasks. In conclusion, identical bimanual tasks facilitate movement of the most affected side in early asymmetric PD at the cost of motor degradation in the least affected side. This observation also highlights the need to perform tasks of bradykinesia in one limb at a time for best accuracy.     

Genotoxicity of some sulfur dyes on tadpoles (Rana hexadactyla) measured using the comet assay.

This report presents the results of a genotoxicity study to evaluate the DNA damage caused by four sulfur dyes used in the textile and tannery industries. Alkaline single-cell gel electrophoresis assay (SCGE) was performed on erythrocytes from Rana hexadactyla tadpoles following whole-body exposure to increasing concentrations of the dyes. The dyes, along with their active ingredients, were Sandopel Basic Black BHLN, Negrosine, Dermapel Black FNI, and Turquoise Blue. The dye-treated tadpoles showed significant DNA damage, measured as mean DNA length:width ratio, when compared with unexposed control animals. Among the four tested dyes Sandopel Basic Black BHLN appears to be highly genotoxic, Dermapel Black FNI was least genotoxic, and Negrosine and Turquoise Blue were moderately toxic to R. hexadactyla tadpoles. The tadpoles showed a significant reduction in DNA damage when placed in dechlorinated tap water after exposure for a 24-hr period to the dye solutions.     

Effect of Cyclic Hormonal Changes During Normal Menstrual Cycle on Esophageal Motility

Pregnancy has an inhibitory effect on motilityof the gastrointestinal tract most likely related toincreased levels of circulating female sex hormones.Similar fluctuations of hormones occur during the normal menstrual cycle, but to a much lesserdegree. We studied the effect of these sequentialhormonal changes on esophageal motility and acidexposure by performing an ambulatory esophagealmotility/pH study (AEM/pH) during the follicular (days 2-4)and luteal phases [days 4-8 after the luteinizinghormone (LH) surge] of the menstrual cycle. Ten normalmenstruating women aged 21-39 years, (mean age 31) were studied with a Konigsberg catheterpositioned such that the pH probe was 5 cm above andpressure transducers 7 and 15 cm above the LES.Ovulation was predicted by LH detection kit, and serumprogesterone levels were obtained in the luteal phase. Eachstudy was performed for 16 hr and included meal,upright, and supine periods. Peristaltic contractionsincreased during the meal periods and decreased during supine periods. Simultaneous and isolatedcontractions increased during supine periods anddecreased with meals. Number and amplitude of distalesophageal contractions did not differ significantlybetween follicular and luteal phase during meal,upright and supine periods. Median percentage of time ofdistal esophageal pH < 4 and median acid clearancewere similar between the two phases. In conclusion, esophageal motility and acid exposure, asmeasured by AEM/pH, are not affected by the hormonalchanges that occur during the menstrual cycle.     

Early laparoscopic repair for supratrigonal vesicovaginal fistula

Laparoscopic repair of supratrigonal vesicovaginal fistula is less morbid and equally effective compared to open repair. This approach is advisable when transvaginal repair is difficult.     

Differential oxidation of mifepristone by cytochromes P450 3A4 and 3A5: selective inactivation of P450 3A4.

The principal enzyme involved in the oxidation of mifepristone is cytochrome P450 3A4 (CYP3A4), which undergoes mechanism-based inactivation by the drug. However, no information is available on the interaction with CYP3A5, the second most abundant CYP3A enzyme in adult human liver. Oxidation of mifepristone by recombinant CYP3A4 produced mono- and didemethylated products and one C-hydroxylated metabolite, as reported previously. However, CYP3A5 produced only the demethylated metabolites. The apparent V(max) and K(M) values for formation of the monodemethylated product by CYP3A4 and CYP3A5 were 46 and 30 nmol/min/nmol P450, and 36 and 16 microM, respectively. Unlike CYP3A4, CYP3A5 was not inactivated by mifepristone. The basis of this differential susceptibility was explored using site-directed mutants in which a CYP3A4 residue was converted to its 3A5 counterpart. Surprisingly, none of these replacements caused a significant decrease in CYP3A4 inactivation by mifepristone. Examination of selected CYP3A4 mutants at 20 other positions indicated that the relative formation rate of the C-hydroxylated product could not account for the differential susceptibility of CYP3A4 and 3A5. Together these results indicate that mifepristone fails to orient itself in the CYP3A5 active site in such a way that its propylenic group is accessible for oxidation, thus rendering CYP3A5 unable to produce the C-hydroxylated product or putative ketene that leads to enzyme inactivation. Identification of mifepristone as a selective mechanism-based inactivation of CYP3A4 may be very useful in distinguishing between the two major CYP3A enzymes collectively responsible for the oxidative metabolism of over half of the drugs currently in use.     

Resolution of pancreatic ascites after low-dose radiation

We have reported a case of pancreatic ascites that responded to low-dose radiation. Our review of the literature and of the limitations of various treatment methods available suggests that low-dose radiation may have a role in the treatment of patients who are at high risk for surgery.     

Comparative assessment of poly-L-aspartic and poly-L-glutamic acids as protectants against gentamicin-induced renal lysosomal phospholipidosis, phospholipiduria and cell proliferation in rats.

Coadministration of poly-L-aspartic acid (poly-L-Asp) protects rats against all measured signs of aminoglycoside nephrotoxicity. Based on in vitro and acute in vivo models, previously we hypothesized that poly-L-Asp protects by forming complexes with the drug in lysomes of proximal tubular cells. However, another closely related peptide, poly-L-glutamic acid (poly-L-Glu), could not protect against gentamicin-induced phospholipidosis and nephrotoxicity, presumably because it is susceptible to rapid hydrolysis in sysosomes in vivo. The present study expands the in vivo comparison between these two polyanions to a subacute model of rats and examines in detail the influence of these polymers on the qualitative and quantitative morphological alterations of lysosomes, phospholipiduria and proliferation of cortical cells induced by gentamicin. Our results not only demonstrated that despite a significantly higher drug cortical accumulation, the coadministration of poly-L-Asp almost completely protects against the development of all these early renal alteration but also pointed to the possibility of a mild, albeit apparently nonlethal, lysosomal thesaurismosis to develop under these conditions. In contrast, poly-L-Glu could not protect against these early renal alterations, though cortical drug accumulation was not significantly higher; however, it induced a conspicuous proliferation of peritubular interstitial cells. Therefore, the present work, taken together with the earlier results of ours as well as that of others, tends to strengthen the hypothesis that the site of action of poly-L-Asp must be in lysosomes, which are also the organelles that sequester and accumulate the drug.     

Stenting of anomalous left carotid artery using a radial artery approach.

A 90-year-old male presented with symptomatic severe stenosis of an anomalous left carotid artery originating from the brachicephalic trunk. A previous attempt at selective cannulation of the left carotid artery was unsuccessful using a transfemoral approach. We performed successful carotid artery angioplasty and stenting using a right radial artery approach.