Therapeutic Advances in the Treatment of Holmes Tremor: Systematic Review

ObjectiveWe aimed to formulate a practical clinical treatment algorithm for Holmes tremor (HT) by reviewing currently published clinical data.Materials and MethodsWe performed a systematic review of articles discussing the management of HT published between January 1990 and December 2018. We examined data from 89 patients published across 58 studies detailing the effects of pharmacological or surgical interventions on HT severity. Clinical outcomes were measured by a continuous 1-10 ranked scale. The majority of studies addressing treatment response were case series or case reports. No randomized control studies were identified.ResultsOur review included 24 studies focusing on pharmacologic treatments of 25 HT patients and 34 studies focusing on the effect of deep brain stimulation (DBS) in 64 patients. In the medical intervention group, the most commonly used drugs were levetiracetam, trihexyphenidyl, and levodopa. In the surgically treated group, the thalamic ventralis intermedius nucleus (VIM) and globus pallidus internus (GPi) were the most common brain targets for neuromodulation. The two targets accounted for 57.8% and 32.8% of total cases, respectively. Overall, compared to the medically treated group, DBS provided greater tremor suppression (p = 0.025) and was more effective for the management of postural tremor in HT. Moreover, GPi DBS displayed greater benefit in the resting tremor component (p = 0.042) and overall tremor reduction (p = 0.022).ConclusionsThere is a highly variable response to different medical treatments in HT without randomized clinical trials available to dictate treatment decisions. A variety of medical and surgical treatment options can be considered for the management of HT. Collaborative research between different institutions and researchers are warranted and needed to improve our understanding of the pathophysiology and management of this condition. In this review, we propose a practical treatment algorithm for HT based on currently available evidence.     

Randomised,placebo controlled,double blind study of alfuzosin SR in patients undergoing trial without catheter following acute urinary retention

INTRODUCTION: Acute urinary retention caused by bladder outlet obstruction resulting from prostatic enlargement is one of the commonest causes for acute admission to urology wards. More recently, there has been a trend to commence treatment with alpha-blockers after catheterisation followed by a trial without catheter (TWOC), in the hope that surgery may be avoided in a significant proportion of patients. There is no conclusive evidence of the efficacy of this treatment. We conducted a study to evaluate the efficacy of using the alpha-blocker alfuzosin SR in patients with acute urinary retention. PATIENTS AND METHODS: All patients presenting with acute urinary retention to our unit were included in the trial. Exclusion criteria included patients with known bladder or prostate malignancy, bladder calculi, urinary tract infections, urethral stricture or patients on alpha-blockers. A total of 81 patients consented and were randomised. Sixty-two patients completed the study. The retention volume was recorded. Trial medicine was recorded on a twice-daily dose and the first TWOC was carried out after a minimum of three doses or 36 hours after admission. TWOC was considered successful on voiding with a residual volume of <200 ml. Unsuccessful patients were recatheterised and discharged home on trial medication, and called for a second TWOC after 2 weeks. Successful patients were continued on alpha-blockers and failures were put on the operating list for TURP. Patients on active treatments were reviewed at 2 year. RESULTS: Of the 34 patients treated with alfuzosin SR, 17 (50%) resumed voiding and of the 28 patients from placebo group, 16 (57%) voided successfully. All 33 patients were continued open labelled on alfuzosin SR 5mg BD. Out of 33 patients, 13 (43%) had TURP within first year after TWOC and three died due to various medical causes. Out of remaining 17 patients, 15 attended for follow-up. The mean peak flow rate was 8.4 ml/s and the mean residual volume was 112 ml. Six patients (40%) required TURP for severe lower urinary tract symptoms (LUTS). So out of 28 patients followed at 2 year, 19 (68%) had TURP. CONCLUSIONS: These data do not support the routine use of alpha-blockers in patients with acute urinary retention. Also continuing use of alpha-blockers does not seem to prevent further requirements of TURP, although larger studies are needed to support this.     

Breast cancer mortality among female radiologic technologists in the United States

We evaluated breast cancer mortality through 1997 among 69 525 female radiologic technologists who were certified in the United States from 1926 through 1982 and who responded to our questionnaire. Risk of breast cancer mortality was examined according to work history and practices and was adjusted for known risk factors. Breast cancer mortality risk was highest among women who were first employed as radiologic technologists prior to 1940 (relative risk [RR] = 2.92, 95% confidence interval [CI] = 1.22 to 7.00) compared with risk of those first employed in 1960 or later and declined with more recent calendar year of first employment (P for trend =.002). Breast cancer mortality risk increased with increasing number of years of employment as a technologist prior to 1950 (P for trend =.018). However, risk was not associated with the total number of years a woman worked as a technologist. Technologists who first performed fluoroscopy (RR = 1.69, 95% CI = 1.02 to 3.11) and multifilm procedures (RR = 1.87, 95% CI = 1.04 to 3.34) before 1950 had statistically significantly elevated risks compared with technologists who first performed these procedures in 1960 or later. The high risks of breast cancer mortality for women exposed to occupational radiation prior to 1950 and the subsequent decline in risk are consistent with the dramatic reduction in recommended radiation exposure limits over time.     

The merits of vascular targeting for gynecologic malignancies

Neovascularization is an early and critical step in tumor development and progression. Tumor vessels are distinct from their normal counterparts morphologically as well as at a molecular level. Recent studies on factors involved in tumor vascular development have identified new therapeutic targets for inhibiting tumor neovascularization and thus tumor progression. However, the process of tumor blood vessel formation is complex, and each tumor exhibits unique features in its vasculature. An understanding of the relative contribution of various pathways in the development of tumor vasculature is critical for developing effective and selective therapeutic approaches. Several such agents are currently in clinical trials, and many others are under development. In this review, the mechanisms and factors involved in tumor blood vessel formation are discussed. In addition, selected novel classes of antivascular therapies, including those targeting tumor endothelial cells and other components of the tumor vasculature, are summarized.     

Adult ADHD and substance abuse: diagnostic and treatment issues

Attention deficit hyperactivity disorder (ADHD) is a neurobehavioral, developmental disorder most often diagnosed during childhood, marked by the core symptoms of inattention, hyperactivity, and impulsivity that results in social, academic, and occupational underachievement. Although the disorder has a prevalence of 3-9% in the general childhood population and 1-5% in the general adult population, it affects between 11 and 35% of "substance-abusing" adults, oftentimes complicating treatment response. The present review discusses diagnostic assessment issues, prevalence, comorbidity, pharmacotherapy, and psychological interventions in substance-abusing adults with ADHD.     

Protein expression profiling of endometriosis: validation of 2-mm tissue microarrays

Tissue microarrays (TMAs) are useful tools for studying protein expression in endometriosis. Tissue microarray analyses of immunohistochemical profiles of estrogen receptor-alpha and P receptor corroborate previously published results from the use of conventional immunohistochemistry, thus validating TMA use in endometriosis.