Methylphenidate for gait impairment in Parkinson disease: a randomized clinical trial.

BACKGROUND: There is a paucity of therapies for gait impairment in Parkinson disease (PD). Open-label studies have suggested improved gait after treatment with methylphenidate (MPD). OBJECTIVE: To evaluate the efficacy of MPD for the treatment of gait impairment in PD. METHODS: Twenty-seven subjects with PD and moderate gait impairment were screened for this 6-month placebo-controlled, double-blind study. Subjects were randomly assigned to MPD (maximum, up to 80 mg/day) or placebo for 12 weeks and crossed over after a 3-week washout. The primary outcome measure was change in a gait composite score (stride length + velocity) between groups at 4 and 12 weeks. Secondary outcome measures included changes in motor function, as measured by the Unified Parkinson's Disease Rating Scale (UPDRS), Freezing of Gait Questionnaire (FOGQ), number of gait-diary freezing episodes, and measures of depression, sleepiness, and quality of life. Three-factor repeated-measures analysis of variance was used to measure changes between groups. RESULTS: Twenty-three eligible subjects with PD were randomized and 17 completed the trial. There was no change in the gait composite score or treatment or time effect for any of the variables. Treatment effect was not modified by state or study visit. Although there was a trend for reduced frequency of freezing and shuffling per diary, the FOGQ and UPDRS scores worsened in the MPD group compared to placebo. There was a marginal improvement in some measures of depression. CONCLUSIONS: MPD did not improve gait and tended to worsen measures of motor function, sleepiness, and quality of life. CLASSIFICATION OF EVIDENCE: This study provides Class III evidence for the lack of benefit of MPD on PD-associated gait impairment. CLINICAL TRIAL REGISTRATION: NCT00526630.

Oxidative stress reproduces placental abnormalities of preeclampsia.

OBJECTIVE: The activities of placental superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px), but not catalase, are lower than normal in preeclampsia, which could contribute to the uncontrolled placental production of lipid peroxides and thromboxane (TX). Oxidative stress, hyperlipidemia and increased iron levels in the maternal compartment in preeclampsia could be responsible for these placental changes by causing oxidative stress in the placenta. METHODS: We tested this possibility in vitro by exposing a trophoblast-like cell line, ED27, to a combination of linoleic acid (LA, 90 microM) and an oxidizing solution composed of hypoxanthine, xanthine oxidase and ferrous sulfate (OxLA) for 6 days. For these studies, the cells were treated with dexamethasone (10-8 M) for the first 72 hr. This was done to differentiate the cells into a phenotype more like syncytiotrophoblast cells as evidenced by production of beta-human chorionic gonadotropin (beta-hCG). RESULTS: After 6 days of exposure to OxLA, the activities of SOD and GSH-Px were significantly decreased as compared to exposure to LA alone. In contrast, catalase activity was increased by OxLA. The OxLA-induced decreases in SOD and GSH-Px activities were attenuated by deferoxamine, an iron chelator, suggesting a role for Fe2+ in the decreased activities. Compared to LA, OxLA significantly increased TX secretion and lipid peroxidation in cells and media at 2, 4 and 6 days. Deferoxamine inhibited the OxLA-induced increase in lipid peroxidation, but not the increase in TX. Isolation of trophoblast cells and villous core tissue from term placentas verified that antioxidant enzyme activity was localized primarily to the trophoblast cell compartment lending validity to the in vitro findings. CONCLUSIONS: These data mimic the changes in placental SOD, GSH-Px, catalase, TX and lipid peroxidation that occur in preeclampsia suggesting that maternal hyperlipidemia and increased iron levels may be responsible for placental oxidative stress and abnormalities in antioxidants and thromboxane.

Placental isoprostane is significantly increased in preeclampsia.

We determined placental tissue levels, production rates, and secretion rates of isoprostanes for placentas obtained from women with normal pregnancies and women with preeclampsia, a hypertensive disorder of pregnancy. Isoprostanes are markers of oxidative stress that exert biological actions such as vasoconstriction. Placental tissue was rinsed and immediately frozen in liquid nitrogen to determine tissue levels of total and free isoprostane. Placental tissue pieces were also incubated in serum-free DMEM for 48 h at 37 degrees C in 95% air/5% CO(2) to determine production rates. Isolated placental cotyledons were perfused for the determination of secretion rates. All samples were analyzed by EIA for isoprostane using an antibody specific for 8-Iso-PGF(2) (15-F(2t)-IsoP). In addition, medium samples were analyzed for malondialdehyde (MDA), a breakdown product of lipid peroxidation. We found that tissue levels of free isoprostane and total isoprostane (free plus esterified forms) were significantly higher for preeclamptic placentas than for normal placentas. Concentrations of isoprostane and MDA in the medium increased progressively during 48 h of incubation of placental explants. At 48 h of incubation, the mean concentrations of both isoprostane and MDA were significantly higher for the placentas from preeclamptic women than for the placentas from normal pregnant women. Concentrations of MDA were highly correlated with those of isoprostane. Induction of oxidative stress with xanthine plus xanthine oxidase increased placental production of isoprostane by normal tissue to a level similar to that of preeclamptic tissue. Placental secretion of isoprostane was eightfold greater toward the maternal side of the placenta than toward the fetal side, and was increased sixfold on the maternal side and twofold on the fetal side by inducing oxidative stress with t-butyl hydroperoxide. This study presents new information that isoprostanes are formed and secreted by the human placenta and provides convincing evidence that oxidative stress and lipid peroxidation are abnormally increased in placentas of preeclamptic women.

Germ cell expression of an isolated human endogenous retroviral long terminal repeat of the HERV-K/HTDV family in transgenic mice.

In contrast to most other human endogenous retroviral families, various HERV-K members have open reading frames that code for functional viral proteins which can form noninfectious particles in some germ cell tumors. The HERV-K viral genes are highly transcribed in germ cell tumors but are transcribed to lower or undetectable levels in most other tissue and tumor types. To further analyze the expression patterns of these proviruses, long terminal repeats (LTRs) were isolated from the human genome and used in reporter gene assays. Expression of some HERV-K LTRs was found to be high in human and murine germ cell tumors (testicular teratocarcinomas) and low in non-germ-cell tumors. Furthermore, upon differentiation of a teratocarcinoma cell line, the expression of an active LTR dropped dramatically, suggesting developmental regulation of these proviral LTRs. Transgenic mice harboring an active LTR driving lacZ expression were generated and analyzed. Adult mouse testes showed the highest levels of expression, and the transgene staining appeared to be restricted primarily to the more undifferentiated spermatocytes. Most other tissues analyzed revealed very low or undetectable levels of expression both by reverse transcription-PCR and by Northern blot analysis. Whether the restricted expression of HERV-K in germ cells and in germ cell-derived tumors is of significant importance during development or tumorigenesis remains to be elucidated. Germ line expression of these viruses would allow for their expansion and movement, while somatic repression would ensure limited insertional mutagenesis and misexpression in an individual.

Incidence of gestational diabetes at Northdale Hospital, Pietermaritzburg.

An incidence study for gestational diabetes was undertaken at Northdale Hospital, which serves a majority Indian and minority Coloured population in Pietermaritzburg. All patients presenting to the antenatal clinic were screened using a 75 g glucose load. If the 1-hour venous plasma glucose level was greater than or equal to 7.8 mmol/l an oral glucose tolerance test (OGTT) was performed. The screening procedure was repeated at 28 - 32 weeks gestation. The OGTT was done with a 75 g glucose load and patients were designated as having gestational diabetes if the 2-hour plasma glucose level was greater than or equal to 7.8 mmol/l. Subsequently, the patients were also evaluated by the 3rd trimester criteria of the Diabetes Pregnancy Study Group of the European Association for the Study of Diabetes (EASD): gestational diabetes being present if the fasting plasma glucose value was greater than or equal to 5.2 mmol/l and the 2-hour plasma glucose value was greater than or equal to 9.0 mmol/l after a 75 g glucose load. Between July 1987 and June 1988 1721 patients were seen. There were 4 pre-gestational diabetics. The remaining 1717 patients were screened for gestational diabetes. Forty-five patients had 2 OGTTs performed, while 251 patients had 1 OGTT in the 3rd trimester. Sixty-five patients had a 2-hour plasma glucose value of greater than or equal to 7.8 mmol/l on OGTT. Hence, the incidence of gestational diabetes using World Health Organisation criteria was 65/1717 (3.8%). Twenty-seven patients had 2-hour plasma glucose value of greater than or equal to 9 mmol/l on OGTT.(ABSTRACT TRUNCATED AT 250 WORDS)

Inhibition of transient gene expression in Chinese hamster ovary cells by cyclobutane dimers and (6-4) photoproducts in transfected ultraviolet-irradiated plasmid DNA.

Using a transient gene expression assay to measure host cell reactivation, the effects of cyclobutane dimer and noncyclobutane dimer uv photoproducts on expression of a reporter gene were examined in normal and repair-deficient Chinese hamster ovary (CHO) cell lines. Ultraviolet damage in plasmid pRSV beta gal DNA, containing the Escherichia coli beta-galactosidase gene, resulted in reduced reporter gene expression in both uv-hypersensitive mutant CHO cell lines UV5 and UV61 relative to wild-type, parental AA8 cells. However, the effects of uv irradiation of transfected plasmid DNA on gene activity were reduced in UV61, a mutant with normal (6-4) photoproduct repair, compared to UV5, which is deficient in (6-4) photoproduct repair; this reduction correlated with the intermediate uv-hypersensitivity of UV61. Selective removal of cyclobutane dimers by in vitro photoreactivation of uv-irradiated plasmid DNA prior to transfection substantially increased reporter gene activity in both uv-hypersensitive mutant cell lines. This increase was significantly greater in UV61 than in UV5, consistent with UV5 being deficient in repair of both (6-4) photoproducts and cyclobutane dimers. These results suggest that unrepaired (6-4) photoproducts in transfected pRSV beta gal plasmid DNA are responsible for a significant fraction of the reduction in transient gene expression observed in recipient uv-hypersensitive CHO cell mutants.

Congenital heart block detected in utero. A case report.

Fetal heart movement and fetal heart rate are easily observed with real-time ultrasonography. Certain aspects of fetal cardiac disorders can thus be further evaluated by M-mode echocardiography. Congenital heart block and associated connective tissue disorders are discussed.

Low-dose cephradine prophylaxis in obstetric and gynecologic surgery.

A short-course, low-dose perioperative prophylactic regimen of cephradine was found to be highly effective in preventing serious postoperative infections (wound, vaginal cuff/pelvic and endometrial) in patients undergoing cesarean sections and vaginal hysterectomies. In patients undergoing abdominal hysterectomy no significant difference was observed in the prevalence of wound and pelvic infections in the antibiotic and placebo-treated groups. In all three operative procedures there was no significant reduction in urinary tract infections. The postoperative length of stay was significantly decreased in cesarean section patients, and a similar trend was observed in vaginal hysterectomy patients. An analysis of risk factors in cesarean section revealed that anemia and labor reduced the effectiveness of prophylaxis. Among vaginal hysterectomy patients those who were anemic and those who were premenopausal were at greater risk of infection. There was a low incidence of adverse drug reactions (less than 0.5%) and no evidence of the promotion of bacterial resistance in cephradine-treated patients.

Cryosurgery for recurrent carcinoma of the vulva: a case report.

Cryosurgery in the palliative treatment of recurrent carcinoma of the vulva is described. A plea is made for the greater use of cryosurgery for this condition in peripheral hospitals.