Effect of Repetitive Transcranial Magnetic Stimulation on Physical Function and Motor Signs in Parkinson's Disease: A Systematic Review and Meta-Analysis.

BACKGROUND: The short-term beneficial effects of repetitive transcranial magnetic stimulation (rTMS) on motor signs in Parkinson's disease (PD) have been addressed by previous meta-analyses while its long-term effects remain undetermined. Although deterioration of walking and upper limb function greatly affects the participation in activities and quality of life of PD sufferers, the effect of rTMS thereon has not been systematically studied. OBJECTIVE: This systematic review aimed to examine the efficacy of rTMS on improving physical function and motor signs over the short- and long-terms in people with PD. METHODS: Five electronic databases were systematically searched for English language full-text articles using relevant search terms. Only randomized placebo-controlled trials investigating the effects of rTMS in PD were considered. The primary outcomes were walking performance, upper limb function, and unified Parkinson's disease rating scale (UPDRS) section III. Trials with similar outcomes were pooled by calculating Hedges' g using random-effects model. RESULTS: Twenty-two trials comprising 555 people with PD were included. Pooled estimates of effect of rTMS indicated significantly improved short-term upper limb function (Hedges' g, 0.40, P = 0.007), short-term (Hedges' g, 0.61, P = 0.03) and long-term walking performance (Hedges' g, 0.89, P = 0.03), short-term (Hedges' g, 0.31, P = 0.003) and long-term (Hedges' g, 0.54, P = 0.003) UPDRS III scores. Subgroup analyses suggest a more prominent effect for M1 stimulation. Meta-regression revealed that a greater number of total stimulation pulses were associated with more UPDRS III improvements over the long-term. CONCLUSION: The pooled evidence suggests that rTMS improves upper limb function in the short-term, walking performance and UPDRS III in the short- and long-terms in PD sufferers. Further studies are required to develop optimal rTMS therapeutic protocols for PD.

Early effective drainage in the treatment of loculated tuberculous pleurisy.

The role of early effective drainage in loculated tuberculous (TB) pleurisy treatment remains unclear. Consecutive patients with TB pleurisy subjected to anti-TB treatment and pigtail drainage (n = 64) were divided into three groups: 1) patients with free-flowing effusions irrigated with saline (free-flowing group; n = 20); 2) patients with loculated effusions irrigated with streptokinase (streptokinase group; n = 22); and 3) patients with loculated effusions irrigated with saline (saline group; n = 22). Pleural irrigation was performed for 3 days consecutively and the effusion drained as completely as possible. Outcomes were assessed for 12 months by clinical symptoms, effusion removed, radiological scores for effusion amount, lung function and occurrence of residual pleural thickening. The total effusion volumes removed were significantly greater in the free-flowing (2.36+/-1.62 L) and streptokinase groups (2.59+/-1.77 L) than in the saline group (1.28+/-1.21 L). Compared with the saline group, the free-flowing and streptokinase groups showed significant improvement in radiological scores and forced vital capacity at different time-points during follow-up, and a significantly lower occurrence of residual pleural thickening. All outcome variables were comparable between the streptokinase and free-flowing groups. In summary, early effective drainage and complete anti-tuberculosis treatment may hasten clearance of pleural effusion, reduce residual pleural thickening occurrence and accelerate pulmonary function recovery in patients with symptomatic loculated tuberculous pleurisy.

Legionnaires' disease in a patient with rheumatoid arthritis.

A 62-year-old male with rheumatoid arthritis (RA) who was taking nonsteroid anti-inflammatory drug for controlling synovitis developed a flare of his arthritis, hepatitis, and pneumonia due to infection with Legionella pneumophila serotype 1. Adult respiratory distress syndrome (ARDS) occurred following the development of pneumonia. After the introduction of erythromycin and ventilator support with positive end expiratory pressure (PEEP), his condition stabilized and he recovered gradually. We suggest that L. pneumophila should be considered early in the differential diagnosis of pneumonia in RA patients due to their immunocompromised status.

Colocalization of prostacyclin synthase with prostaglandin H synthase-1 (PGHS-1) but not phorbol ester-induced PGHS-2 in cultured endothelial cells.

The subcellular colocalization of prostacyclin synthase (PGIS) with prostaglandin H synthase (PGHS) has not been delineated. To test the hypothesis that its colocalization with PGHS is crucial for prostacyclin synthesis, we determined subcellular locations of PGIS, PGHS-1, and PGHS-2 in bovine aortic endothelial cells by immunofluorescent confocal microscopy. PGIS and PGHS-1 were colocalized to nuclear envelope (NE) and endoplasmic reticulum (ER) in resting and adenovirus-infected bovine aortic endothelial cells. PGIS and PGHS-2 were also colocalized to ER in serum-treated or adenovirus-cyclooxygenase-2-infected cells. By contrast, PGIS was not colocalized with PGHS-2 in cells induced with phorbol 12-myristate 13-acetate where PGHS-2 was visualized primarily in vesicle-like structures. The lack of colocalization was accompanied by failed prostacyclin production. Resting ECV304 cells did not produce prostacyclin and had no detectable PGHS-1 and PGIS proteins. Confocal analysis showed abnormal colocalization of PGIS and PGHS-1 to a filamentous structure. Interestingly, the abundant PGIS and PGHS-1 expressed in adenovirus-infected ECV304 cells were colocalized to NE and ER, which synthesized a large quantity of prostacyclin. These findings underscore the importance of colocalization of PGHS and PGIS to ER and NE in prostacyclin synthesis.

Expression of Th2 cytokines and the stable Th2 marker ST2L in the absence of IL-4 during Leishmania major infection.

In this study we characterized Th2 responses in the absence of IL-4. We show that ST2L, a stable Th2 marker, is expressed at similar levels in Leishmania major-infected IL-4-deficient (IL-4(-/-)) and wild-type BALB/c (IL-4(+/+)) mice. Th2 cytokines are secreted by in vivo differentiated lymphocytes in response to specific activation in the absence of IL-4. Although IL-13 is produced, its neutralization did not alter the outcome of infection. Thus, we demonstrate that Th2 differentiation as assessed by the expression of ST2L and the production of Th2 cytokines can occur in vivo in the absence of IL-4.

Interleukin-12 is capable of generating an antigen-specific Th1-type response in the presence of an ongoing infection-driven Th2-type response.

Previously we demonstrated that recombinant murine interleukin-12 (rmIL-12) administration can promote a primary Th1 response while suppressing the Th2 response in mice primed with 2,4, 6-trinitrophenyl-keyhole limpet hemocyanin (TNP-KLH). The present studies examined the capacity of rmIL-12 to drive a Th1 response to TNP-KLH in the presence of an ongoing Th2-mediated disease. To establish a distinct Th2 response, we used a murine model of leishmaniasis. Susceptible BALB/c mice produce a strong Th2 response when infected with Leishmania major and develop progressive visceral disease. On day 26 postinfection, when leishmaniasis was well established, groups of mice were immunized with TNP-KLH in the presence or absence of exogenous rmIL-12. Even in the presence of overt infection, TNP-KLH-plus-rmIL-12-immunized mice were still capable of generating KLH-specific gamma interferon (IFN-gamma) as well as corresponding TNP-specific immunoglobulin G2a (IgG2a) titers. In addition, the KLH-specific IL-4 was suppressed in infected mice immunized with rmIL-12. However, parasite-specific IL-4 and IgG1 production with a lack of parasite-specific IFN-gamma secretion were maintained in all infected groups of mice including those immunized with rmIL-12. These data show that despite the ongoing infection-driven Th2 response, rmIL-12 was capable of generating an antigen-specific Th1 response to an independent immunogen. Moreover, rmIL-12 administered with TNP-KLH late in infection did not alter the parasite-specific cytokine or antibody responses.

Second trimester maternal serum screening using alpha fetoprotein, free beta human chorionic gonadotropin and maternal age specific risk: result of chromosomal abnormalities detected in screen positive for Down syndrome in an Asian population.

BACKGROUND: This study was to determine the incidence of chromosome abnormalities in Taiwanese women undergoing prenatal chromosome analysis after a second trimester Down syndrome screening by using maternal age and serum dual-marker testing (alpha-fetoprotein and free-beta unit human chorionic gonadotropin). METHODS: A total of 10,098 Taiwanese women with pregnancy between 15 and 23 weeks' gestation received second-trimester Down syndrome risk evaluation by dual-marker and maternal age specific risk testing in a single medical center. The study took 22 months. Ninety-seven percent of this study population was less than 34 years old. Ninety-six percent of our cases were screened between 15-20 weeks of gestation. This population was included only after a routine ultrasonography scan for correction of gestational age and exclusion of major structural anomalies. By using an algorithm to detect Down's syndrome, with a risk of 1:270 as a cut-off value, 816 patients were screen-positive for Down syndrome (screen-positive rate 8.0%). Karyotypes were reviewed for 670 (82.1%) mothers who received prenatal karyotype analysis. RESULTS: Twelve cases of Down syndrome were identified in the screen positive group with an estimated detection rate of 67% (false positive rate 8%). Three cases of Down syndrome were detected in late trimester among the screen-negative group. Seven other fetal chromosome abnormalities were also found among the screen-positive pregnancy. In addition, seven cases were screen-positive for trisomy 18; all of these patients received amniocentesis and only one case was confirmed. CONCLUSION: These findings indicate that this screening program combining alpha-fetoprotein (AFP), free beta human chorionic gonadotropin (free-hCG) and maternal age-specific would achieve a screening efficiency in Taiwanese populations as comparable to those obtained in Caucasian populations. Our results also suggest that approximately 3% of pregnancies with a positive dual marker and maternal age-specific screen results will have a chromosome abnormality despite having a normal routine ultrasound scan. Mothers with positive screening results should be made aware of the implications of a positive result.

Tuberculous meningitis in a Filipino maid.

Tuberculous meningitis, while not uncommon in Taiwan, has not been reported among foreign workers. We report the first case of tuberculous meningitis in a 37-year-old Filipino maid in Taiwan, who presented with headache, fever and vomiting. She had been well before this episode and the small screening films of the chest radiograph obtained on her arrival in Taiwan 15 months previously, and every 6 months thereafter showed no evidence of tuberculosis. The suspicion of tuberculous meningitis was delayed until disturbance of consciousness manifested and a standard chest radiograph showed a diffuse miliary pattern in both lung fields. A cerebrospinal fluid sample that was sent for a polymerase chain reaction-based assay specific for Mycobacterium tuberculosis showed a positive result. The patient recovered with sequelae of mildly incoherent speech and urinary incontinence after antituberculous medication and short-course steroid treatment. Clinicians should be aware of the possibility of tuberculous meningitis in foreign workers with complaints of fever and headache. Because high-quality chest radiographs are a prerequisite for early detection of pulmonary tuberculosis, we recommended that standard posterior-anterior chest radiographs should be obtained as part of the routine health examination for foreign workers.

Thoracoamniotic shunting for treatment of fetal bilateral hydrothorax with hydrops.

Isolated bilateral pleural effusion with mediastinal compression leading to hydropic change of the fetus is unusual, and carries a high risk of perinatal death. This condition can be reversed in utero by performing ultrasound-guided shunting surgery. We describe a hydropic fetus at 30 weeks' gestation with rapid recurrence of pleural effusion after thoracentesis. The pleural effusion and hydrops resolved within 1 week after ultrasound-guided thoracoamniotic shunt and the fetal lungs were restored to their normal size. The fetus was born at 35 weeks' gestation and had an uneventful postnatal course. The technique of restoring cardiopulmonary function in utero through intrathoracic decompression offers a valuable alternative to repetitive prenatal thoracentesis or preterm delivery of fetuses with hydrops caused by bilateral pleural effusion.

The role of recombinant murine IL-12 and IFN-gamma in the pathogenesis of a murine systemic Candida albicans infection.

Studies on murine candidiasis suggest that resistance to disease is linked to a Th1 response and production of IFN-gamma, while failure to elicit protection is associated with a Th2 response and production of IL-4 and IL-10. Experimental infection of C57BL/6 mice, IL-12 treatment of these mice, or both infection and IL-12 treatment resulted in a characteristic Th1 cytokine mRNA profile as measured by quantitative competitive PCR. Specifically, little or no IL-4 transcripts were detected, while IFN-gamma message was elevated, particularly with IL-12 treatment. Despite its role in driving increased IFN-gamma expression and production, IL-12 treatment, paradoxically, promoted disease progression in our model. Therefore, we examined the effect of IFN-gamma neutralization on IL-12-induced susceptibility to infection. None of the systemically infected mice receiving IL-12 alone survived, while IL-12- and anti-IFN-gamma-treated mice had a 70% survival rate, similar to that after infection alone. These results suggested that IFN-gamma induced by IL-12 treatment contributed to lethality. However, in separate studies, IFN-gamma knockout mice were more susceptible to infection than their wild-type counterparts, suggesting that IFN-gamma is required for resistance. Nonetheless, infected IFN-gamma knockout mice treated with recombinant murine IL-12 exhibited enhanced resistance, suggesting that the toxicities observed with IL-12 are directly attributable to IFN-gamma and that an optimal immune response to Candida infections necessitates a finely tuned balance of IFN-gamma production. Thus, we propose that although IFN-gamma can drive resistance, the overproduction of IFN-gamma during candidiasis, mediated by IL-12 administration, leads to enhanced susceptibility.

[The density and larval habitats of dengue vectors in Chungho city].

A survey was conducted to understand larval habitats and density of dengue vectors in Chungho city during the period of August 12 to September 13, 1996. Most villages (41 in the total of 93) were found to have the density figures of three for Aedes albopictus Skuse. The second common density figures were found at 2nd and 4th levels. The most common breeding containers found were less than 5 cm in water depth and less than 100 cm2 in water area. The number of breeding containers reduced when the water depth and size increased. The common breeding containers in villages were flower vases (30%) and water buckets (18%). In the mountains, water buckets (34%) and kitchen tools (11%) were common. In parks, water buckets (29%) and tires (15%) were commonly found. In cemeteries, the common breeding containers were flower vases (57%) and earthenware pots (17%). The average (2.05 containers per man-hour) of positive water containers in the mountains was significantly higher than that in parks (0.62). However, the average in cemeteries (1.29) was not significantly different from those collected in mountains and parks.

Prenatal diagnosis of congenital cystic adenomatoid malformation of the lung: four cases report.

Congenital cystic adenomatoid malformation of the lung (CCAML) is a rare pulmonary lesion, characterized by excessive overgrowth of the terminal respiratory bronchioles. Prenatal detection and serial sonographic study of fetuses with CCAML can provide information about the natural history of these lesions and reveal most of the nature history of pathophysiologic features which are likely to affect the clinical outcome. This information is crucial to the formulation of a prognosis and a management strategy. We report on four cases of CCAML, three of which involved macrocystic lesions including two cases of type I and one case of type II. Only one microcystic lesion, a type III CCAML, was identified in these patients. All of the cases were diagnosed by ultrasound between the 21 and 24 weeks of gestation. Fetal hydropic change was noted in all four cases. All of the parents opted for termination of pregnancy before fetal viability. Post-mortem examination confirmed the diagnosis in all four cases.

[Primary surveillance of spotted fever group antibodies on rats in the Kinmen area].

The positive rate of rickettsial antibodies of 107 rats in the Kinmen area by indirect immunofluorescent antibody (IFA) technique was 0% (0/107) in typhus fever, 38.3% (41/107) in scrub typhus and 66.4% (71/107) in spotted fever group; the positive rate (42.9%) of spotted fever group of 21 rats in Taiwan island also higher than scrub typhus (19.0). It suggests that spotted fever group patients may be present in our country but have not been discovered.

Obstetrical hysterectomy and placenta previa/accreta: three bladder injury case reports.

Pregnancies complicated with placenta previa and a history of cesarean section are well known to be at increased risk for placenta accreta. Bladder injury is occasionally encountered in these patients during operation. From January 1992 to December 1995, 25 obstetrical hysterectomy were performed at Chang Gung Memorial Hospital, Linkou Medical Center. Of these 25 patients three had bladder injury. Ultrasonography is a unique way to screen and detect prenatally the abnormal placentation and intraplacental lacunae. Color Doppler ultrasonic scanning further discloses that the lacunae are mainly venous spaces. Elevated mid-trimester maternal serum x-fetoprotein (MSAFP) frequently leads to a suspicion of the abnormal placentation, and magnetic resonance imaging (MRI) can clearly identify the placenta accreta/increta. Uncontrollable bleeding frequently occurs in these patients during cesarean section, warranting emergency hysterectomy. Emergency obstetrical hysterectomy should be decided upon and performed by an experienced obstetrician. Massive hemorrhage and bladder injury are the major complications encountered in such operations. We review the literature and propose a protocol of management. As the incidence of cesarean section continues to rise world-wide, the problem of placenta previa/accreta is likely to become more common. Obstetricians should be ready to face the late sequelae of today's decision for cesarean section.

Resolution of cutaneous leishmaniasis: interleukin 12 initiates a protective T helper type 1 immune response.

Resistance to Leishmania major in mice is associated with the appearance of distinct T helper type 1 (Th1) and Th2 subsets. T cells from lymph nodes draining cutaneous lesions of resistant mice are primarily interferon gamma (IFN-gamma)-producing Th1 cells. In contrast, T cells from susceptible mice are principally Th2 cells that generate interleukin 4 (IL-4). Although existing evidence is supportive of a role for IFN-gamma in the generation of Th1 cells, additional factors may be required for a protective response to be maintained. A potential candidate is IL-12, a heterodimeric cytokine produced by monocytes and B cells that has multiple effects on T and natural killer cell function, including inducing IFN-gamma production. Using an experimental leishmanial model we have observed that daily intraperitoneal administration at the time of parasite challenge of either 0.33 micrograms IL-12 (a consecutive 5 d/wk for 5 wk) or 1.0 micrograms IL-12 per mouse (only a consecutive 5 d) caused a > 75% reduction in parasite burden at the site of infection, in highly susceptible BALB/c mice. Delay of treatment by 1 wk had less of a protective effect. Concomitant with these protective effects was an increase in IFN-gamma and a decrease in IL-4 production, as measured by enzyme-linked immunosorbent assay of supernatants generated from popliteal lymph node cells stimulated with leishmanial antigen in vitro. The reduction in parasite numbers induced by IL-12 therapy was still apparent at 10 wk postinfection. In addition, we observed that the administration of a rabbit anti-recombinant murine IL-12 polyclonal antibody (200 micrograms i.p. every other day for 25 d) at the time of infection to resistant C57Bl/6 mice exacerbated disease. These effects were accompanied by a shift in IFN-gamma production in vitro by antigen-stimulated lymph node cells indicative of a Th2-like response. These findings suggest that IL-12 has an important role in initiating a Th1 response and protective immunity.

Mechanisms of ionophore-induced stimulation of renin secretion with special reference to a chemiosmotic hypothesis.

The effects of several ionophores on renin secretion were investigated in rabbit renal cortical slices. When slices were incubated in the absence of Ca++, the K+ ionophore valinomycin (10(-5) approximately 5 x 10(-4) M) or the monovalent cation ionophore nonactin (10(-4) M) stimulated renin secretion about 2-fold. The renin secretion stimulated by valinomycin was further increased by inclusion of the H+ ionophore, carbonylcyanide m-chlorophenylhydrazone. The electroneutral K+/H+ exchange ionophore nigericin (10(-5) approximately 5 x 10(-4) M) stimulated renin secretion in a dose-dependent manner, producing a maximal stimulation of about 17-fold. Another electroneutral exchange ionophore, monensin, also significantly stimulated secretion. The stimulation by both valinomycin and nigericin was apparent whether slices were incubated in Na(+)-rich or K(+)-rich media. The extent of stimulation by the two ionophores was dependent upon the presence of anion with acetate greater than Cl greater than isethionate greater than thiocyanate. Thiocyanate itself markedly inhibited renin secretion. Incubating of slices in an iso-osmotic ammonium acetate medium which is known to induce rapid swelling of secretory granules, stimulated renin secretion to the magnitude comparable to that of maximal stimulation by nigericin in a potassium acetate medium. The pattern of response to these ionophores indicates that changes in K+, H+ and anion gradients across the renin secretory granule may modulate renin secretory rate. It is proposed that conditions which allow accumulation of K+ and anion within acidic renin secretory granules lead to osmotic swelling of the granules and that granule swelling may promote exocytosis.

[Dengue vector density survey in Liuchiu, Pintung, Taiwan].

The first outbreak of dengue in Taiwan in 35 years was recorded in the summer of 1981 in Liuchiu, Pintung, a small offshore island of southern Taiwan. An investigation team visited the affected area during the period of 14-17 October 1981 and collected 8,641 mosquito larvae, of which 4,432 were Aedes aegypti and 4,182 were Ae. albopictus. The house index, container index and Breteau index were 44.2, 23.9 and 73.0 for Ae. aegypti and 41.3, 17.0 and 51.9 for Ae. albopictus, respectively. Both species of mosquitoes are peridomestic breeders, with larvae found in water-holding containers in or outside houses. Ae. albopictus is indigenous, but Ae. aegypti may be of recent introduction to the island. As the two species are closely related, the larvae of both species were found co-existent in only 2.3% of positive containers. This supports the hypothesis of the "competitive exclusion principle", i.e., competition is possibly occurring on this island.